R21 grants


2009.06.14 08:36 sexxihair Grants

Welcome to Grants! Ask any questions and share any info here about grants.

2020.06.11 03:45 SPIDER-MAN-2 21stCenturyHumour

21stCenturyHumour 🇬🇧💂, The peak of the best humour on earth.

2011.07.08 22:54 scubanarc Grants Pass, Oregon


2023.03.17 22:39 CB9611 While looking for a certain tool, I found this at my local auto store

While looking for a certain tool, I found this at my local auto store submitted by CB9611 to cyberpunkgame [link] [comments]

2023.01.11 16:34 mbster2006 FYI - NIH Funding for Toxicology Research

Got an email about these toxicology-focused FOAs so thought it might be worth sharing with fellow toxicologists here -
  1. PAS-21-245: Limited Competition: Promoting a Basic Understanding of Chemical Threats to Skin (R34 Clinical Trial Not Allowed)
  2. RFA-ES-21-006: CCRP Initiative: Chemical Threat Agent-induced Pulmonary and Ocular Pathophysiological Mechanisms (R01 Clinical Trial Not Allowed)
  3. RFA-DA-23-056: Chemical Countermeasures Research Program (CCRP) Initiative: Basic Research on The Deleterious Effects of Acute Exposure to Ultra-Potent Synthetic (UPS) Opioids (R01 Clinical Trial Not Allowed)
  4. PAR-23-027: CCRP Initiative: NIH Countermeasures Against Chemical Threats (CounterACT) Basic Research on Chemical Threats that Affect the Nervous System (R01 Clinical Trial Not Allowed)
  5. PAR-20-253: Countermeasures Against Chemical Threats (CounterACT) Exploratory/Developmental Projects (R21 Clinical Trial Not Allowed)
  6. PAR-22-209: CCRP Initiative: Countermeasures Against Chemical Threats (CounterACT) Therapeutics Discovery and Early-Stage Development (UG3/UH3 Clinical Trial Not Allowed)
Seems to be a big NIH focus - "The National Institutes of Health Chemical Countermeasures Research Program (NIH CCRP): A collaborative opportunity to develop effective and accessible chemical medical countermeasures for the American people"
submitted by mbster2006 to toxicology [link] [comments]

2022.08.18 05:57 billskelton Geelong is set to field 3x300 game players (Selwood, Hawkins, Dangerfield). Just the third trio to ever do it. (Useless AFL Stats)

Geelong is set to field 3x300 game players (Selwood, Hawkins, Dangerfield). Just the third trio to ever do it. (Useless AFL Stats) submitted by billskelton to AFL [link] [comments]

2022.07.21 09:19 Purine_Simple Please help me decide whether MD/Ph.D is the path for me

This thread has been incredibly helpful, as I've read quite a few posts here. I am here because I am torn between applying to MD only programs versus MD programs focusing on training "physician-scientists" (e.g. UPitts PTSP or Stanford's Berg Scholars) versus applying to traditional MSTP programs.
I have a strong background in research and absolutely love research and plan to go into academia (easier said than done, of course). I know most will see this as me being naïeve, but I know my intended specialty and subspeciality as it's pretty niche. & I am confident that this is the field that I want to study for several reasons: 1). I have a masters in this area and contemplated getting a Ph.D. in this area, but I ultimately decided that I want to have patient interaction as a part of my career. Therefore I need the M.D., and my research interests are more along the translational side of research. 2). I completed my Fulbright research within this field and found that it lent itself very well to my ideal research style and had quite a few areas I would be interested in exploring so I could never get bored. Also, I have more personal reasons why I want to conduct research in this area.
So here is my thought process after speaking with MANY individuals, and I would love some objective thoughts...
Firstly, a little background and a couple of caveats. I am NOT interested in conducting basic science research using animals. I have worked with animals at the undergraduate and graduate levels and quickly discovered I d not work with them PERSONALLY. I understand entirely why animal models are needed to advance science, however, I despise working with them. Therefore, ideally, I would like to partner with a Ph.D. to conduct any animal experiments needed.
Ideally, I am interested in running a clinical immunology lab similar to the type of work I completed during my Fulbright. We essentially had a lab consisting of MDs and Ph.D. partnered with a basic science-only lab for animal work. Our lab recruited patients, completed biobanking, ran immunophenotyping, and ELISAs, helped create new techniques etc., to identify possible cell populations of interest and other potential disease biomarkers. We then partnered with the basic science lab to develop animal models that could help us test our hypotheses. And finally, if we identified anything of interest in the animal models, we could then use that to ultimately translate our insights into viable therapeutic options for patients (bedside to bench to bedside or reverse translational research).
So now pros and cons:
  1. MD: Pros are I don't have to work with animals anymore, and I can develop the clinical background necessary for my research interests. The timeline is also much more streamlined and I could, in theory, complete a research residency or post-doc following residency to acquire the necessary research skills. The cons would be the price associated with medical school and the very real chance that I would be viewed as not having enough research experience to be taken seriously enough to break off into academia and be competitive for NIH grants (e.g., K awards or an R01 or R21).
  2. MD programs with physician-scientist focus (e.g., UPITT): Pros, I could get more in-depth training in translational science, and I get protected research time without having to devote 3-4+ years to earn a Ph.D. that I am not entirely sure is needed for my particular career path. Also since most programs like this are five years in length the 2-3+ years saved could also be used to do a research residency or postdoc to acquire any skills I am lacking. Plus, with this type of program, I would get a little more flexibility with my project, and since it is only a year, I could stomach doing something that is not directly related to my ultimate research interest as long as I develop relevant skills and techniques that could benefit my research in the future. Whereas in an M.D/Ph.D. I don't think I could handle 3-4+ years of not enjoying my project just to gain relevant skills.
  3. MSTP programs: The main pro is the dedicated research time where I can devote most, if not all, of my time to developing my research skills while also not having to worry about mind-boggling debt following my training. The lack of debt would make a career in academia much more appealing as you're not constantly worried about paying off 300-400k in loans on an academic salary. Also, the dual training is beneficial in research. My PI is an MD/Ph.D. and another mentor is an MD only, so I am privileged to have worked with both on research projects. Their thinking is different (one is not inherently better), just different. Both perspectives were needed, but the M.D./Ph.D is always a little more interested and honestly more skilled in accessing how the actual study will need to be set up (e.g., identifying confounding variables, making sure that the scientific problem being addressed is not only clinically relevant but scientifically feasible and what particular methods would be best to study the problem, whereas the M.D. is more interested in the method of data collection, data analysis, and the overall clinical utility and less of the nitty gritty experimental design, especially the animal model portion.) Again, both perspectives are needed, one is just more interested in the experimental design and can seemingly switch between the clinical and experimental thought process more seamlessly.
Lasly, my ideal set up would be at an academic center where I see patients maybe 1-2 days/week and conduct research the remainder of my time, so ideally a 70/30 split. I know this is a lot but I am in need of help as much as possible.
submitted by Purine_Simple to mdphd [link] [comments]

2022.07.20 14:43 TheFscientist Advice needed to approach/write my first R21 or R03 grant (USA) while I am still under the supervision of another PI

I am an assistant scientist and I convinced my PI to have a meeting next week to go over data and to look at the possibility of writing a R21 or R03 grant. I was promoted from research associate to assistant scientist a few months ago, after an exodus of other postdocs to industry. I want to think that my PI understood that postdocs/research associates need mentoring/career guidance and not only the graduate students. Now, I wondering how to successfully handle writing a NIH grant without hurting egos or make my PI feels threaded by me. I just want the grant to be successful and to stay in the lab with my PI many more years.
submitted by TheFscientist to AskAcademia [link] [comments]

2022.05.21 20:05 NewProf2022 New Prof Startup Spending

Hi! I'm a postdoc who's just been offered a position as biology-chemistry assistant professor at a medium-large USA teaching college. Yay!
The school tells me that they want me to be research heavy and want me to help push forward the research department. So they are giving me some startup funds. My ideas revolve around cell biology, biochemistry, and molecular biology (Edit - I have a specific idea in mind which I want to investigate and the area is a sweet spot of high funding but not super crowded). I have roughly $100k to startup my research but i'm going to push for a little more. Unfortunately the labs don't have a lot at the moment, but things are moving forwards with some federal grants. We can also get some time at the big famous college across town and occasionally use their flow cytometer and confocal microscope for free (Edit - among other equipment, but i'm not sure what yet).
I'm trying to pool together some ideas - what do you guys think are some essential items I should buy and budget for? I was thinking of getting a LiCor Odyssey XF as a big item because they don't have an imager at all (just film) and I think LiCor match education startup grant funding up to 40%. So maybe $25-30k for that. This'll also hopefully make me popular in the department as people will want to use it, and then I can get favors and use their equipment! There's a piece of specialist equipment I need for the types of experiments i'll be doing and that is $7k.
So $65k left to get my research going and hopefully I can support it further with institutional grants (if we get the federal grants) or my own R03/R21/R01/K01.
Does anyone have any ideas? Thank you!
submitted by NewProf2022 to labrats [link] [comments]

2022.03.28 07:51 SAtechnewsbot R21.9 Million Grants: African Entrepreneurs Invited To Enter Jack Ma Competition

R21.9 Million Grants: African Entrepreneurs Invited To Enter Jack Ma Competition submitted by SAtechnewsbot to SAtechnews [link] [comments]

2022.01.28 12:47 JuniperPublishers-CC Targeted Pharmacological Heme-Oxygenase-1 Induction as a Therapy for Diabetes-Juniper Publishers

Targeted Pharmacological Heme-Oxygenase-1 Induction as a Therapy for Diabetes-Juniper Publishers
Juniper Publishers-Journal of Cardiology


Diabetes has emerged as a major threat to health worldwide. The exact mechanisms underlying the disease are unknown; however, there is growing evidence that excess generation of reactive oxygen species (ROS), causes oxidative stress in various organs. In diabetic patients, oxidative stress is closely associated with chronic inflammation and plays a key role in the pathogenesis of micro-and macrovascular diabetic complications. Redox reactions associated with carbon monoxide (CO) metabolism play key roles in intra- and inter-cellular signaling. Cells produce significant amounts of CO as a product of cellular metabolism, largely from heme degradation catalyzed by microsomal heme oxygenases (HOs) generating CO, biliverdin, bilirubin and iron. This review focuses on the importance of both HO-1/CO system in the pathophysiology and therapy of inflammation associated with diabetes. Research on these pathways will open new perspectives for the rational design of drugs against diabetic diseases.
Keywords: Diabetes; Oxidative stress; Reactive oxygen species; Heme-oxygenase-1; Carbon monoxide


Diabetes is a chronic disease characterized by elevated blood sugar levels resulting from either a lack of insulin production or resistance to insulin. About 230 million people worldwide had diabetes in 2010. The global figure of people with diabetes is projected to increase to 333 million in 2025, and 430 million in 2030 [1]. The majority of diabetes patients are not insulin- dependent and able, at least initially, to produce the hormone. This type of diabetes mellitus (DM) is termed type 2 diabetes. Insulin resistance is a fundamental aspect of the etiology of type 2 diabetes. Subjects with diabetes have an increased risk of ischemic heart disease, atherosclerosis and nephropathy [2,3].Obesity, which is a major public health concern worldwide,increases the risk of type-2 diabetes [3]. Type 2 diabetes is caused by a combination of insulin resistance coupled with insufficient production of insulin to overcome the insulin resistance [4]. Oxidative stress plays a key role in the pathogenesis of micro-and macrovascular diabetic complications. There is now convincing evidence that redox reactions associated with CO metabolism play key roles in adaptive processes of tissues towards oxidative stress. Cells and tissues produce significant amounts of CO from heme degradation catalyzed by microsomal heme oxygenases (HO).

Heme Proteins as Signaling Molecules

Heme proteins play a major role in various biological functions and most of the reactions involving heme are redox reactions of heme iron. Heme is released from hemoproteins during red blood cell (RBC) destruction and is metabolized by heme oxygenases (HO). Three isoforms of HO have been characterized: an inducible form (HO-1), which is up-regulated, especially in the spleen and liver, in response to various types of stress, and two constitutive forms (HO-2 and HO-3). HO-1 generates signaling molecules through the catalysis of heme-carbon monoxide (CO), biliverdin, bilirubin and iron-each of which acts via distinct molecular targets to influence cell function, both proximally and distally. An excess of heme is deleterious to cells. The damage caused is due to its iron-induced prooxidant effects on all of the compounds of cells; these toxic effects are caused by iron catalyzing the Fenton reaction. Biliverdin reductase (BVR) has two isoforms: BVR-A and BVR-B. Through the activity of BVR, BV is immediately reduced to bilirubin. Extensive research has shown that the HO and BVR systems are closely involved in the molecular regulation of various pathophysiological processes, in particular in cellular adaptation to oxidative stress, and the anti-inflammatory response. In some circumstances, normal homeostatic regulatory mechanisms may be overwhelmed by the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) such as nitric oxide (oNO) with input from co-factors. The major antioxidant enzymes possess transition metals, selenium, manganese, riboflavin or ubiquinone at the catalytic site and the availability of cofactors can determine the activity of some enzymes [5]. Susceptibility to oxidative processes increases with age and with disease as a result of the deterioration of normal physiological control [6]. There is now convincing evidence that redox reactions associated with NO and CO metabolism play key roles in intra-and inter-cellular signaling, and in adaptive processes of tissues towards stress [7]. It is now well recognized that HO-mediated heme degradation has multiple roles, including antioxidant and iron reutilization functions. HO generates the effector molecules biliverdin/ bilirubin, carbon monoxide, and free iron/ferritin.

Oxidative and Nitroxidative Stress in Diabetes

Given the multiplicity of their functions, mitochondria are a logical target for the study of metabolic diseases. Skeletal muscle is the major site of insulin-stimulated glucose use in the body, and the dysregulation of mitochondria is closely associated with insulin resistance in skeletal muscle and thus with the pathogenesis of type 2 diabetes. Inside mitochondria, electrons from reduced substrates move from complexes I and II of the electron transport chain through complexes III and IV to oxygen, forming water and causing protons to be pumped across the mitochondrial inner membrane. The electron transport system is organized so that the level of ATP can be precisely regulated [8].
The increased superoxide anion production is associated with the activation of major pathways involved in the pathogenesis of diabetic complications: 1) polyol pathway flux, 2) increased formation of AGEs, 3) activation of protein kinase C isoforms, and 4) over-activity of the hexosamine pathway. The accelerated flux of sorbitol through the polyol pathway has been implicated in the pathogenesis of secondary diabetic complications: cataractogenesis, retinopathy, neuropathy, nephropathy and cardiovascular diseases. In addition, in diabetic rats, levels of free carnitine and myo-inositol in the caudal nerves are decreased while polyol accumulates. These actions are accompanied by the inactivation of enzymes such as eNOS [9]. Insulin exerts redox- regulating actions in various target organs, implying that the hormone has an antioxidative role [10]. The generation of ROS by mitochondrial oxidative phosphorylation is attenuated by insulin through the regulation of uncoupling protein (UCP) expression. In addition, the expression of NADPH oxidases (NOX) is inhibited by insulin [11]. In cultured adipocytes, excess glucose and palmitate generate ROS via NOX4 rather than by mitochondrial oxidation. NOX4 is regulated by both NADPH generated in the pentose phosphate pathway and translocation of NOX4 into lipid rafts, leading to the expression of monocyte chemotactic factors [12].

Heme Oxygenases and Endogenous Production of Carbon Monoxide

Biological systems rely on heme proteins to carry out a number of basic functions: such as oxygen sensing, electron transport, signal transduction, and antioxidant defense enzymes. Most of these reactions are carried out by redox reactions involving heme iron [13]. Heme biosynthesis includes several steps. The first and the last three steps occur in mitochondria; while the others take place in the cytoplasm [14]. Heme is released from hemoproteins during red blood cell (RBC) destruction and metabolized by HO. The majority of heme degradation products are derived from the catabolism of hemoglobin released from senescent RBCs, phagocytosed, and destroyed by the reticuloendothelial (RE) system, primarily in the spleen and liver. The oxidation of heme by the HOs requires the concerted activity of nicotinamide adenine dinucleotide phosphate (NADPH)-cytP450 reductase to provide reducing equivalents to support the reduced state of iron (Fe2+) and to activate molecular oxygen [15]. Humans possess control mechanisms to maintain iron homeostasis by coordinately regulating iron absorption, iron recycling, and mobilization of stored iron [16]. In humans, endogenous CO arises principally from the action of HO, which catalyzes the rate-limiting step in heme degradation. The HO reaction generates one molecule of CO per molecule of oxidized heme. HOs play an important physiological role in hemoglobin turnover in reticulo-endothelial tissues such as the spleen, kidney and liver where senescent erythrocytes are destroyed [17].

Functions of Heme Oxygenases

Three isoforms of HO have been characterized: an inducible form (HO-1), which is up-regulated, in response to various types of stress, and two constitutive forms (HO-2 and HO-3).

Heme oxygenase-1: HO-1

The inducible form of HO, HO-1, occurs at a high level of expression in the spleen and other tissues that degrade senescent red blood cells, including specialized reticulo-endothelial cells of the liver and bone marrow. HO-1 is also present in myeloid cells. These cells comprise monocytes, macrophages and dendritic cells, which play crucial regulatory roles in the innate and adaptive immune system. As the liver plays a crucial role in the body's iron homeostasis (e.g. via secretion of the iron regulatory hormone: hepcidin) and in systemic inflammation, hepatic HO-1 may be important for the regulation of both systems. In an organ such as the liver, the induction of HO-1 expression is an important aspect of the anti-inflammatory, anti-apoptotic response to cellular stress. The gene coding for HO-1 is highly regulated [18,19]. HO-1 is emerging as a great potential therapeutic target for treating cardiovascular diseases. In the vascular system, HO-1 and heme degradation products perform essential physiological functions [20]. There appears to be a relationship between HO-1 expression and the signaling pathways that modulate inflammatory response[21]. Nitrated fatty acids (NO2-FA) resulting from interactions between NO and eicosanoid have distinct anti-inflammatory signaling properties. Nitrated linoleic acid potently induces HO-1 expression by an NO- and PPARy-independent mechanism in human aortic endothelial cells [22]. These pathways may converge via the generation of nitrated unsaturated lipids that influence PMN activity and the evolution of inflammation [23].

Heme oxygenase-2: (HO-2)

HO-2 is constitutively expressed in selected tissues (brain, liver, and testes) and is involved in signaling and regulatory processes. HO-2 has three cysteine residues that are thought to modulate the affinity for heme, whereas HO-1 has none [24]. Within the normal liver, HO-2 is constitutively expressed within hepatocytes, Kupffer cells, endothelial cells and Ito cells. In the central nervous system, it has been demonstrated that HO-2 can function as an O2 sensor in the brain, and the O2-CO-H2S cascade rapidly mediates hypoxia-induced cerebral vasodilation [25].

Heme oxygenase-3: (HO-3)

The existence of a third HO isoform, HO-3, was reported in the rat. HO-3 was shown to be the product of a single transcript of 2.4kb encoding a protein of 33kDa. The HO-3 transcript was found in a series of organs including spleen, liver, kidney and brain [26]. The function of HO-3 remains unclear, but it has been cloned from rat brain, suggesting a neural function. This enzyme is structurally similar to HO-2, but is less efficient at degrading heme.

Incidence of Endogenous HO-1 Activation

The incidence of endogenous HO-1 activation has been studied in experimental and clinical procedures. HO-1 activity provides a possible antioxidative function by accelerating the removal of heme to limit oxidative stress sustained through heme-iron dependent mechanisms. The effects of CO and bilirubin indirectly reproduce the incidence of HO activation. Great attention has been paid to the protective role of CO and carbon monoxide-releasing molecules (CORMs) in vascular diseases. Indeed, CO and CORMs exert anti-inflammatory and anti-oxidant actions on different organs [27,28]. Bilirubin appears to be a more potent antioxidant than biliverdin. Nonetheless, there is evidence that the direct and indirect antioxidant effects of both bile pigments contribute to the beneficial profile of the HO-1 pathway. Individuals with Gilbert's syndrome have polymorphism in the bilirubin UDP-glucuronosyltransferase (UGT1A1) promoter and are protected against a number of factors associated with cardiovascular complications. This polymorphism results in slower glucuronidation and therefore diminished excretion of bilirubin, leading to elevated bilirubin levels in the plasma.
Recent studies have revealed that HO-1 mediates the adiponectin-induced anti-inflammatory response; adiponectin inducing an HO-induction [29]. Adiponectin, an adipokine predominantly secreted from adipocytes, plays a modulatory role in various pathophysiological conditions. Apart from its well characterized role in glucose and fatty acid metabolism, adiponectin has received special attention in recent years due to its protective role in inflammation. Moreover, chronic HO-1 induction also modifies the phenotype of adipocytes in obesity from large, cytokine-producing adipocytes to smaller, adiponectin-producing adipocytes [30]. Emerging evidence indicates that links exist between HO activity and the changes in energy metabolism that occur during the development of certain diseases. Experimental evidence suggests that excessive amounts of free fatty acids and high glucose produce hypertrophied adipocytes resulting in detrimental perturbations in both mitochondrial and endoplasmatic reticulum function. These effects are associated with the increased generation of ROS, activation of the inflammatory cascade and insulin resistance. The levels of HO-1 expression, HO activity and its products, CO and bilirubin, are decreased in humans and in animal models of type-2 diabetes [31]. In conclusion, the induction of HO-1 appears to modulate metabolic syndrome, obesity, and insulin resistance, and recent data provide evidence for the involvement of the HO- adiponectin-EET axis in adipogenesis and adipocyte signaling both in vitro andin vivo [32].

Heme-Oxygenases Inducers (Table 1)

A lot of natural agents have been recognized for their capacity to induce HO-1 in different tissues. Most of these compounds are characterized by a phenolic structure, similar to that of alpha- tocopherol, and present antioxidant properties.

Natural heme-oxygenase-1 inducers

A number of natural antioxidant compounds contained in foods and plants have been demonstrated to be effective non- cytotoxic inducers of the response protein HO-1 in various cellular models. Most of these compounds that induce HO-1 are characterized by phenolic structures and it is speculated that Nrf2 is involved in this induction of HO-1 [33]. The effects of various concentrations of a natural polyphenolic stilbene, resveratrol, on HO activity and HO-1 protein expression in different experimental conditions have been tested. Resveratrol is a non- flavonoid compound produced naturally by plants including grapes, peanuts, cranberries and blueberries. Resveratrol is the major polyphenol in red wine and has been shown to prevent or slow the progression of a wide variety of diseases [34]. The most extensively investigated HO-1 inducer is another natural compound, curcumin (diferuloylmethane). The effects or curcumin are associated with cellular protection against ROS. The level of HO-1 expression was found to highest with curcumin, followed by demethoxycurcumin and bis-demethoxycurcumin. It has been suggested that the presence of methoxyl groups in the ortho-position on the aromatic ring are essential to enhance HO-1 expression [35].

Pharmacological interest approach of HO-1 inducers

Manipulation of the Nrf2/HO-1 pathway has been shown experimentally to protect against a variety of conditions characterized by oxidative damage and inflammation. Pharmacologically-active compounds have been used to target Nrf2/HO-1. Potent activators of the Nrf2/HO-1 pathway (i.e. carnosol, cobalt protoporphyrin, dimelthyl fumarate) have been shown to modulate inflammation in mouse microglial cells [36]. Metalloporphyrins, particularly cobalt protoporphyrin (CoPP) can increase the expression of HO-1. CoPP affects the expression of antioxidant genes and recent data indicate that CoPP reduces mitochondrial production mediated by Foxo1 [37]. A large number of clinical and experimental pharmacological compounds have been shown to induce HO-1, via NO metabolism. The different statins with established antiatherogenic or cardioprotective activities are able to induce HO-1 [38]. NOreleasing compounds, such as sodium nitroprusside, S-nitroso-N- acetylpenicillamine, and 3-morpholinosydnonimine, induce HO-1 in endothelial cells [39]. Studies suggest that aspirin may exert part of its antiinflammatory effect via the NO-mediated induction of HO-1 [40]. The increase in HO-1 expression in response to other compounds is the result of a complex regulatory network involving many signaling pathways and transcription factors. Pharmacological doses of insulin have been reported to induce HO-1 in renal cells via the phosphatidylinositol 3-kinase/Akt pathway and Nrf2 and this may represent a mechanism by which insulin protects the kidney in addition to its effect on circulating glucose concentration [41,42].


Extensive research has shown that the HO system is closely involved in the regulation of various pathophysiological processes, in particular in cellular adaptation to oxidative stress, and the anti-inflammatory response. It is now well recognized that HO-mediated heme degradation has multiple roles, including antioxidant and iron reutilization functions. The multiple cytoprotective mechanisms of HO-1 make it a promising therapeutic target. Regulation of HO-1 activity may be a therapeutic strategy for a number of inflammatory conditions and it may be important to explore the overall protective roles of the HO-1/CO system in the pathogenesis of human cardiovascular and vascular diseases.


This work was supported by grants from French Ministry of Research, Inserm (Institut national de la sante et de la recherche medicale) and, from the Regional Council of Burgundy Franche Comte (Conseil Regional de Bourgogne et de Franche Comte), FEDER and Association de Cardiologie de Bourgogne.
For more Open Access Journals in Juniper Publishers please click on: https://juniperpublishers.com/open-access.php
For more articles in Open Access Journal of Cardiology & Cardiovascular Therapy please click on: https://juniperpublishers.com/jocct/index.php
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2022.01.06 08:02 AnythingElseMatters 2022 January -- Significance of vitamin A to brain function, behavior and learning

Retinoid acid, the bioactive metabolite of vitamin A, is a potent signaling molecule in the brains of growing and adult animals, regulates numerous gene products, and modulates neurogenesis, neuronal survival and synaptic plasticity. Vitamin A deficiency (VAD) is a global health problem, yet our knowledge of its effects on behavior and learning is still emerging. Here we review studies that have implicated retinoids in learning and memory deficits of post-embryonic and adult rodent and songbird models. Dietary vitamin A supplementation improves learning and memory in VAD rodents and can ameliorate cognitive declines associated with normal aging. Songbird studies examine the effects of retinoid signaling on vocal/auditory learning and are uniquely suited to study the behavioral effects of VAD because the neural circuitry of the song system is discrete and well understood. Similar to human speech acquisition, avian vocal learning proceeds in well-defined stages of template acquisition, rendition and maturation. Local blockade of retinoic acid production in the brain or excess dietary retinoic acid results in the failure of song maturation, yet does not affect prior song acquisition. Together these results yield significant insights into the role of vitamin A in maintaining neuronal plasticity and cognitive function in adulthood.
Keywords: Learning, Neuromodulation, Neuronal plasticity, Retinoic acid, Vitamin A

1 Introduction

Vitamin A is a fat-soluble micronutrient that is converted into retinoic acid at or near the site of activity in the body for use as a transcriptional regulator. Microarray studies have found retinoid signaling to affect a large number of genes in different tissues [13], and by some estimates affects ~15% of known human protein-coding genes [4], thus represents a strong candidate for neuromodulation. Vitamin A deficiency (VAD) is globally one of the most common forms of malnutrition in human populations, with ocular disorders, immunosuppression and impaired growth commonly described [5], and although considerable political efforts have been undertaken to eliminate VAD over the last half-century [5] it today remains a problem in much of the developing world [6, 7]. In light of the recent attention of micronutrients to human cognition, a lack of a strong role for vitamin A is surprising [8, 9]. However, based on evidence from animal models and associative human studies, a significant role of vitamin A is likely. For instance, the acne-control drug, Accutane (a retinoic acid analogue), was recently discovered to reduce hippocampal neurogenesis and proliferation, along with the ability to learn a maze in adult mice [10], while in humans the incidence of depression is ~10% higher among Accutane users [11]. Thus, use of therapeutic retinoids likely has effects on the maturation and maintenance of the adult brain and associated behaviors (though subtle compared to the dramatic effects on embryonic development). Supplementation of vitamin A or retinoid derivatives as therapeutic agents has been widely proposed for psychiatric pathologies including schizophrenia and Alzheimer’s disease [12], and may be used for controlling certain cancers [13, 14]. In light of animal models that show how retinoid signaling affects neuronal maintenance and behavior, we review work that has altered retinoid signaling up or down in the brains of rodents and songbirds with subsequent neurobiological effects that are tied to a specific cognitive function or complex behaviors.

2 Vitamin A and retinoic acid metabolism

The biologically active metabolite of vitamin A, retinoic acid, is the ligand of a set of receptors (retinoic acid and retinoid × receptors) that act as transcriptional regulators restricted to chordates, and it is best known as a signaling molecule during early embryogenesis [15, 16]. However, tightly controlled retinoid signaling is also important throughout adolescence and adulthood, and has been shown to play various roles in the continued formation, differentiation and maintenance of neuronal phenotypes. Owing to its low stability and low abundance in neuronal tissue, retinoic acid has proved challenging to effectively quantify by methods such as HPLC [17], but recent improvements in direct retinoic acid quantification [18] may prompt its quantification in sub-regions of the brain. Rather, retinoid signaling in the brain has often been inferred by the presence of aldehyde dehydrogenase, the terminal enzyme in the retinoic acid synthesis pathway. Three retinaldehyde-specific aldehyde dehydrogenases (RalDH) are present in high levels in the embryo and/or occur in the developing eye [19], but the isoform RalDH2 remains prevalent in post-embryonic and adult brains at lower levels. In embryos, differential expression of RalDHs sets up diffusion gradients of retinoic acid across structures such as the whole body plan, limb bud or eye. These gradients broadly determine patterns of structure formation [20, 21]. However, because adults and juveniles have greater physical structural complexity and lower levels of RalDH2 expression in their bodies than embryos, the spatial scale in which gradients of retinoic acid may act is not clear. It is likely with lower concentrations of retinoic acid present in tissues, concentration gradients must occur across a smaller space, perhaps over several cells. In addition, several gene products in addition to RalDH2, including cellular retinoic acid-binding proteins and retinal dehydrogenases/reductases, and cytochrome degradation enzymes provide additional regulatory control of retinoic acid levels [22, 23], and these regulatory gene products may change with development. Since RalDH2 is expressed by fully differentiated neurons in adults, retinoic acid may be produced in the functional cell bodies of one brain region for axonal transport to other remote regions where it may then direct neuromodulation. In either scenario, poorly understood transport processes and much smaller spatial fields of retinoid signaling are likely the norm in post-embryonic tissues, further necessitating the need for a tightly controlled system of retinoid signaling to maintain critical neuronal function.
Experiments to investigate the actions of retinoid signaling on neural properties and behaviors have either downregulated (e.g. simulated VAD) or upregulated retinoid signaling in the brain. VAD models may be achieved with the use of synthetic diets that are deficient in retinoic acid and all potential retinoic acid precursors, or the synthesis of retinoic acid may be disrupted by pharmacological blockers of retinoic acid synthesis [24]. Research with rodents has employed a transgenic knockout model for the retinoic acid receptor [25], and with the recently released songbird genome [26] in combination with development of viral transfection to generate transgenic songbird models, this may soon be a realistic technique for songbird researchers. Conversely, vitamin A and/or retinoic acid supplementation provides a model to better understand the therapeutic effects of retinoid signaling. This approach complements VAD as it results in excess retinoic acid levels in the brain. This is a significant approach as frequently both deficits of retinoid signaling and overproduction of retinoic acid can have disruptive effects, resulting in a detectable phenotypic response.

3 Rodent studies of neuromodulation by retinoic acid

Rodents models have proven informative on the effects of retinoid signaling on post-embryonic neuromodulation as retinoids affect hippocampal long-term depression (LTD) and potentiation, both measures of long-lasting synaptic plasticity, and neurogenesis [12, 27, 28]. The first clear evidence that retinoids play a role in cognitive function came from work with knockout mice that lacked either one of the retinoic acid receptors, RARβ, or one of the retinoid × receptors, RXRγ [25]. These particular receptors are uniquely expressed in hippocampal regions of the adult mouse brain that are implicated in spatial and relational memory, whereas the other retinoic acid receptors and retinoid × receptors are more uniform in their distribution. Thus, mutant mice for these receptors showed normal development and growth with no abnormal physical or neuronal morphology, yet demonstrated cognitive deficits in learning the Morris water maze and impaired motor control and balance, compared to wild-type mice. These behavioral impairments correlated with electrophysiological differences in hippocampal CA1 cells in that RARβ mutants lost long-term potentiation (LTP) and the RARβ and RXRγ mutants both lost LTD. Both of these correspond to changes in long-term synaptic efficacy that can affect learning and memory.
Following these findings, several studies have demonstrated a dietary link between retinoids and behavior or neuronal plasticity. By experimentally inducing VAD in neonatal mice, Misner et al. [29] showed that poor retinoid nutrition also affects LTP and LDP in mice, along with the more obvious physical and ocular deformities typical of VAD. These electrophysiological effects occurred without apparent physical differences in the underlying neuronal structure of the hippocampus, and in fact when proper retinoid nutrition was returned to retinoid-deprived mice, LTP and LTD returned to normal [29]. Behaviorally, dietary VAD in rodents also results in cognitive declines in memory tasks, but unlike the apparent rescue effect of supplemental retinoids for electrophysiological function, the behavioral rescue effect was not as consistent in all animals as there continue to be age-related effects on susceptibility to VAD. For instance, in a two-arm discrimination maze (baited with food) young VAD mice demonstrated persistent exploratory behaviors over a training period that is characteristic of naive animals, compared to normal mice that readily go to food after they learn the maze [30], and these effects do not go away when normal diets return, compared to older animals. Species differences are also evident: in contrast to mice, rats deprived of vitamin A at an early age showed cognitive decline that seems to improve once a regular diet is resumed [31, 32].
In parallel to the deprivation experiments, high doses of the 13-cis retinoic acid isomer administered to adult mice also results in cognitive deficits, and are correlated with reduced cell proliferation in the hippocampus and the proliferative regions of the ventricle [10]. Thus, excessively high levels of retinoic acid also have detrimental effects, suggesting that it needs to be regulated within a narrow concentration range. The maintenance of the adult olfactory bulb also requires retinoid signaling and is known for high levels of neuronal plasticity in terms of adult neurogenesis or variable profiles of gene expression [33]. Furthermore in a mouse model of Alzheimer’s disease that overexpresses genes for β-amyloid and presenilin 1, mice can be rescued from Alzheimer’s-related learning deficits by therapeutic all-trans retinoic acid (ATRA) administration [34]. ATRA-treated mice showed fewer of the neurodegenerative β-amyloid deposits in their brains, yet the possibility exists that the cognitive improvements were unrelated to the decrease in β-amyloid deposits, as aged wild-type mice that are given retinoic acid also show improvements in their cognitive abilities [35]. Indeed, therapeutic retinoid tools are promising for nervous system injuries, age-related declines in cognitive function as well as dementia-associated diseases; however, because of the multiple gene/signaling pathways and multiple aspects of neuronal plasticity known to be affected by retinoid signaling, careful research is needed.

4 Avian studies of retinoic acid neuromodulation

While rodent models best address spatial and relational memory, the songbird model addresses vocal and auditory learning, a trait shared with humans but that is not possible to test with most other mammal models, including nonhuman primates. Besides being one of the few organisms that evolved vocal learning, songbirds are powerful models for examining the neural basis of vocal learning because the brain areas that control song are composed of a series of discrete nuclei that have been well-characterized anatomically and physiologically [36, 37]. Birdsong consists of a learned complex vocal-motor sequence that is reinforced through sensorimotor learning during a critical period of high neuronal plasticity in the song system of juveniles [38]. Young zebra finches (Taeniopygia guttata) that hear song from male tutors during the Sensory Acquisition Period (20–60 days post hatch [dph]; Fig. 1) will acquire a stored template of the tutor’s song in their memory. They then enter the Sensorimotor Phase (~40–90 dph) where individuals develop their songs by matching the highly variable song that they produce to that of the tutor’s song stored in their memory. By adulthood (~90 dph) their songs mature and “crystallize” to the point that variability is minimal and the songs that they produce show a strong resemblance to that sang by their tutors [39]. In zebra finches these critical periods are well characterized [38] and this model provides a system that closely resembles the acquisition of human speech where infants first exhibit variable babbling, followed by experimentation with the sounds and pronunciation of spoken language [40].
📷Figure 1
Timeline of critical periods within the zebra finch (T. guttata) song development and patterns of zRalDH expression in the song nuclei HVC, LMAN and RA (see text for proper names) of the zebra finch brain.
The avian song system consists of several well-defined song nuclei that function in two complementary circuits. Birdsong begins in the song nucleus HVC (hyperstriatum ventrale, pars caudalis), which originates the neuronal pathways that are responsible for the learning and the production of song (Fig. 2). Projection neurons from the HVC to the robust nucleus of the arcopallium (RA) begin the posterior vocal-motor pathway and provide direct control to vocal and respiratory motor neurons (Fig. 2, black arrows). The anterior pathway originates as projection neurons from HVC to area X of the medial striatum (gray arrow), and from there sequentially to the dorsal lateral nucleus of the medial thalamus and to the lateral magnocellular nucleus of the nidopallium (LMAN) and into RA. Retinoic acid production in adults seems to be tightly linked to this anterior pathway. The large neurons that originate in the HVC and project to area X (Fig. 2, shown as a gray arrow) and the large neurons within LMAN are major sources of zRalDH (the zebra finch analog of RalDH2) expression in the adult song system, while song nucleus RA shows only a transient expression pattern in juveniles that disappears by 50 dph (Fig. 1). By 4 dph zRalDH is detectable within HVC, LMAN and RA and levels gradually increase as these song nuclei grow. During this time, neuronal connections among the song nuclei are being established and new cells are migrating in from the proliferative regions along the ventricle. zRalDH expression in RA is characteristic of juvenile songbirds between ~10 and 50 dph and levels peak at ~38 dph [41] which corresponds to the invasion of HVC projection neurons into the RA [42] and the first attempts at song in the juvenile. While zRalDH in the RA is largely absent after 50 dph, its expression continues in HVC and LMAN into adulthood, indicating a persistent production of retinoic acid in the adult song system [41].
📷Figure 2
(A) Parasaggital view of direct and anterior pathways of the zebra finch (T. guttata) song system. Bold arrows show the direct motor pathway, while thin arrows delineate the anterior forebrain loop. Projections and nuclei that are known to express zRalDH are shown in gray, and nuclei with no expression are shown in white. (B) In situ hybridization of antisense riboprobe for the zRalDH shows strong expression in HVC and in the nidopallial layer of the telencephalon, including LMAN.
The anterior pathway is responsible for song learning in juveniles and for modulating plasticity in learned song in adults. For instance, ablation of LMAN during the critical period of juvenile song acquisition reduces variability in juvenile song prematurely and inhibits learning ability [43, 44]. Thus, this circuit contributes to the neuronal and behavioral plasticity that is necessary to learn a complex behavior such as song. Our lab has altered retinoid signaling in the songbird brain with the application of pharmacological blockers of retinoic acid synthesis locally over HVC [41]. Disulfiram disrupts the final step in the synthesis of retinoic acid production by inhibiting retinaldehyde-specific zRalDH, while expression of other known class 1 aldehyde dehydrogenases does not occur in the songbird brain [24]. Birds treated with disulfiram at 30–35 dph (compared to controls who received saline implants in HVC or disulfiram implants in another brain region) showed evidence of song acquisition from a tutor male, but songs remained variable into adulthood, with frequent omission or variability of song elements into adulthood, indicating that maturation and crystallization did not occur. Song of disulfiram-treated birds resembled closely the variable song of juveniles, with poor note morphology and instability of fast frequency modulations. In contrast, adult birds with disulfiram placed over their HVCs showed no detrimental effects to their already crystallized songs [41].
In a similar study, male finches were supplemented with a high daily dose of ATRA (oral administration in corn oil vehicle between 30 and 120 dph) to test for possible changes to the qualities of their song compared to controls given vehicle alone [45]. Songs were recorded at 120 dph to analyze vocal development and the brains were examined for the expression of several candidate retinoid-regulated genes. ATRA-treated birds sang a complex song that contained normal features of conspecific song, including a motif with syllables that were presumably copied from the adult songs in the aviary. However, based on the analysis of multiple consecutive renditions (minimum 10 motifs per bird), the songs of ATRA-treated birds demonstrated more variability than controls. These songs had lower consistency, linearity and stereotypy [46], indicating lower levels of syntactic stereotypy compared to controls. These effects were largely due to frequent note additions and/or omissions in comparison with the most typical motif for each bird, as well as higher variability in the duration of syllables and inter-syllabic intervals than in controls. ATRA-treated birds also had lower similarity and accuracy scores [47]. The lower scores in the ATRA-treated group reflect higher variability in several acoustic features (such as pitch, spectral continuity, entropy) across multiple song renditions for each individual. In sum, songs from ATRA-treated birds resembled the plastic song of juveniles. Thus, song maturation appears to be arrested prior to song crystallization when retinoid signaling is upregulated through dietary supplementation, similar to birds where the production of retinoic acid was locally blocked in HVC [41]. In both scenarios of increased and decreased retinoid levels, birds show elements of song acquisition, but fail to crystallize their songs.
These results raise several important questions regarding the roles of retinoid signaling on genetic and cellular processes in the song system during the juvenile song-development period and over the adult life-span. Retinoic acid drives neuronal differentiation by effects on gene expression [21, 23], thus in the context of the song system, genes with differential expression in the HVC and that are shown to be affected by changes in retinoic acid levels, are likely to have important effects on the development of the song system. Indeed, microarray studies that have examined positive or negative induction of genes in tissues such as breast carcinoma tissue, Xenopus larva and lymphoid tissue have yielded different patterns of induction among the various systems [13]. Thus, neuronal tissue is likely to have a unique induction of genes in response to changes in retinoic acid levels, compared to other tissues. Four genes, (neurogranin) nrgn, BMP/RA-inducible neural-specific protein brinp1 (a.k.a. dbc, deleted in bladder cancer in humans) and a retinal short-chain dehydrogenase/reductase, sdr2/scdr9, retinoic acid receptor alpha, rar-α, have shown altered expression in the brain with the previously described feeding trial [45]. Of these brinp1 and nrgn have prominent expression in HVC – nrgn is associated with synaptic development and remodeling [48, 49] and decreases in HVC in response to ATRA, while brinp1 is an inhibitor of the cell cycle, possibly through the TrkC/NT3 receptor [50] and shows broad increases in neural tissues in response to ATRA. The function of both these genes is consistent with a role in modulating different kinds of neuronal plasticity in the song system, in fact, a positive linear relationship was shown between nrgn expression levels in both LMAN and area X with the degree of song stereotypy. Retinoic acid is known to modulate neuronal proliferation, migration, differentiation and synaptic connectivity, but at this point we know little about how genetic programs directed by retinoic acid drive these cellular processes in the avian song system. In terms of the histological structure of the song system and volume of song nuclei there are no apparent effects of altered retinoid signaling [45], similar to a lack of an effect in the volume of the murine hippocampus [29]. Sdr2/scdr9 has low expression in the song system, but shows increased expression with increased levels of retinoic acid in area X and LMAN of the anterior loop of the song system, consistent with a likely role of this gene product in providing an inhibitory regulatory role in retinoic acid signaling.

5 Concluding remarks

Even though this is a relatively new area of research, the evidence strongly suggests that vitamin A, through its main metabolite retinoic acid, continues to exert important actions on brain physiology and behavior in post-embryonic and adult life. Avian and murine studies suggest that a balance of retinoic acid is required to attenuate the behavioral plasticity that is required for the storage and recovery of memory. That is, levels of retinoic acid are maintained at moderate levels by a complex of control mechanisms and feedbacks, so that too much or too little of this ligand will result in similar deficits in learned behaviors. However, it is still unclear how underlying pathways of retinoic acid signaling change with different levels of the ligand and how this differs in different neuronal systems. Retinoic acid is broadly implicated in neurogenesis, cell differentiation, synaptic connectivity and electrophysiological potentiation – all processes that affect what we commonly think of as neuronal plasticity. Furthermore, neurobiological systems may respond to retinoic acid differently at various stages of development, but additional work is needed to fully understand this issue. In terms of learned behavior, plasticity is required for neural systems to be able to adapt to broad and constantly changing environmental conditions, yet excessive plasticity may be detrimental for an animal to effectively learn and consolidate very specific patterns, particularly behaviors as complex as learned vocalizations.
The studies discussed here indicate the continued importance of vitamin A as a nutrient for the brain not only during embryonic development but also during adulthood. The study of retinoic acid effects on the song system offers a unique opportunity to identify the molecular regulators of a complex behavior such as vocal learning. With the avian song system, we have detailed knowledge on the composition and physiology of specific neuronal elements, and thus presents an opportunity to identify the retinoic acid targets at a cellular and molecular level. Overall, research in basic model organisms to further our knowledge of how vitamin A affects the brain and behavior will expand our understanding of the significance of VAD to human populations in terms of learning ability. This is significant as measuring cognitive abilities across multiple cultures is notoriously difficult.
The decline in cognitive ability is one of the classic hallmarks of human aging, and in animal models under conditions of poor vitamin A nutrition. Resumption of vitamin A and proper levels of retinoic acid signaling may have restorative effects, but again, research to identify the extent of possible recovery and the critical periods during the life stage is needed. Indeed, VAD at early stages in the life cycle of rodents seems to have irreversible effects on the brain, but adult animals may be more tolerant to episodes of retinoid malnutrition [31]. Compared to short-lived rodents, birds are very long-lived for their body sizes [51], and thus may be an appropriate model for the long-term effects of VAD in humans. Therapeutic doses of retinoic acid may ameliorate age-related dementia and psychosis, yet may also exert undesirable effects on the brain through other pathways. Further studies on animal models like rodents and songbirds are poised to further reveal the importance of vitamin A and retinoid signaling for brain function and behavior.


This research was supported by grants 2R01-DC002853 for C.V. Mello and 1F32-NS062609 for C.R. Olson. The authors’ use of animal models for research is covered under the OHSU IACUC ]0721. This review benefited from the thoughtful comments of K.L. Horback and two anonymous reviewers.


ATRA all-trans retinoic acid
HVC hyperstriatum ventrale, pars caudalis
LMAN lateral magnocellular nucleus of the nidopallium
LTD long-term depression
LTP long-term potentiation
RalDH retinaldehyde-specific aldehyde dehydrogenases
RA robust nucleus of the arcopallium
VAD vitamin A deficiency


The authors have declared no conflict of interest.
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2021.10.12 19:39 Wapulatus Respect Seiya Ryuuguuin! (Cautious Hero)

"I’m perfectly prepared."

Seiya Ryuuguuin


Summoning Japanese teenagers into alternate worlds of fantasy has become such a common occurrence in the vast, interconnected multiverse, that the gods that govern it make names for themselves isekai'ing people and saving more and more difficult worlds.
One of these gods, the goddess of healing Ristarte, is assigned one of the highest difficulty worlds to save from the Demon Lord - S-Class. In a panic over saving a world so high above her paygrade, she scours through her options before finding a one-in-a-million individual, with starting statistics that would make it a cakewalk to save even difficult worlds. In her haste to summon him, however, she failed to read the fine print that was his personality...
"Overly Cautious."

Source Guide

Light Novel Thread Manga Thread Anime Thread
Light Novel feats are sourced with Volume and Chapter. Note that chapters are numbered per arc, not per volume (ex. chapter numbers continue to increase between Vol 1-2, the Gaeabrande Arc).
Web Novel feats from unpublished chapters utilize fan translations, and are marked with the overall chapter.
Feats marked with [Berserk] signify Seiya was using a power amplifying skill he gained in the series' second arc. Some feats are marked and organized by the series arc it took place in, this is because his skills and levels reset at the beginning of them.


Note that named attacks are listed separately below under "Skills", many of which incorporate physical force or speed.


Corrupted Worlds


Corrupted Worlds


Corrupted Worlds

Gaeabrande Arc Spells/Skills

Skills and Magic used by Seiya in the first Arc, which comprises the first two novels.
Note that there's some overlap with later arcs, as he occasionally goes back to using his fire magic and sword skills.


Sword Skills

Phoenix Drive
Phoenix Thrust
Eternal Sword
Atomic Split Slash
Wind Blade

Fire Magic/Skills

Hellfire / Maximum Inferno
Automatic Phoenix
Meteor Strike
Fire Salamanders (Corrupted Worlds Arcs)

Shining Arrow

Ixphoria Arc Spells/Skills

Skills and Magic used by Seiya in the second arc, which comprises the volumes 3-5.


Earth Magic

Earth Serpents
Stone Golems
Mega Rista
Cave Along
Clear Ceiling
Endless Fall
Great Iron Wall
Bomb Boulders

Jolly Piper Skills

Other Elemental Magic


Spirit/Ghost Skills

Corrupted Worlds Arc Spells/Skills

Skills and Magic used by Seiya in the current third arc, which comprises everything from Volume 6 onwards. Note that Seiya no longer loses his levels and skills when moving from one world to another, now, although he's still bound by the rules of that world.

Ice Magic

Fenrir Shot


Dark Magic

Phantom Hands
Infect Lover
Death Confession

Holy Magic

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2021.10.01 14:56 JuniperPublishers-CC Spinal Cord Injury: An Under Recognized Cardiovascular Disease Risk Factor-Juniper Publishers

Spinal Cord Injury: An Under Recognized Cardiovascular Disease Risk Factor-Juniper Publishers
Juniper Publishers-Journal of Cardiology


Keywords: Stroke; Coronary artery disease; Paraplegia; Tetraplegia


Spinal cord injury (SCI) is a devastating, life-changing condition causing paralysis and sensory impairment as well as autonomic dysfunction. In addition, evidence documents a state of chronic inflammation in individuals with SCI [1-4]. Importantly, chronic inflammation is a significant cardiovascular disease risk factor. Furthermore, paralysis can lead to a relatively sedentary life style and a consequent reduction in physical work capacity [58]. Other consequences of inactivity are a higher body weight, a higher percentage of body fat [9,10], skeletal muscle dysfunction [11-14] and a lower forced vital capacity [15-17].
Autonomic dysfunction involves an abnormal and unstable regulation of the of the heart and vasculature [18]. Specifically, hypotension occurs immediately after the injury because of loss of tonic supra-spinal excitatory drive to spinal sympathetic neurons [19]. Subsequently, resting arterial pressure returns toward normal values; however, episodic bouts of hypertension often develop as part of the condition termed autonomic dysreflexia (AD) [20,21]. If not treated promptly, the hypertension may produce cerebral and subarachnoid hemorrhage, seizures, and renal failure and may lead to death [22]. Furthermore, autonomic dysregulation of the heart alters cardiac electrophysiology and increases the susceptibility to arrhythmias [23].
The overwhelming consequences of SCI-induced paralysis often overshadows the fact that inactivity, chronic inflammation and autonomic dysfunction increase the risk of stroke, coronary heart disease, diabetes and, possibly death [9,24-30]. Specifically, individuals living with SCI have an increased risk of heart disease and stroke [31]. Furthermore, individuals living with SCI have a three-fold greater risk of developing cardiovascular disease (CVD) than their able-bodied counterparts [31]. Importantly, the magnitude of CVD risk is heavily dependent on the level of SCI, whereby individuals with tetraplegia have a 16% greater risk of all-cause CVD than individuals with paraplegia [32-35]. As noted, the risk for significant cardiovascular disease is mediated, in part, by reduced physical inactivity, dyslipidemia, blood pressure irregularities, chronic inflammation, and abnormal glycemic control [1-3,28,36-49].
Despite this increased risk of cardiovascular disease [31,50], many health care providers are unaware of the complications associated with SCI [51-56] as there is generally little undergraduate or postgraduate training on SCI [52,54,56,57]. Even knowledge of life threatening conditions, such as autonomic dysreflexia, are unknown among many physicians outside the rehabilitation or neurologic specialties [58]. Thus, additional information regarding the cardiovascular risks associated with SCI has the potential to improve the quality of life for individuals and families living with SCI. An understanding of the unique medical conditions related to SCI is an important first step because cardiovascular complications are important and potentially serious conditions.
In summary, individuals living with spinal cord injury have an increased risk for heart disease and stroke. Furthermore, cardiovascular disease is the leading cause of death and morbidity. The risk for cardiovascular disease is associated with an unstable autonomic control of the heart and vasculature, a relatively sedentary lifestyle, chronic inflammation and blood lipid profiles consisting of elevated total and low-density lipoprotein cholesterol and depressed high-density lipoprotein. Relative inactivity associated with SCI also results in a reduced muscle mass and increased adiposity. Accordingly, individuals living with SCI often experience insulin resistance, hyperinsulinemia and an atherogenic profile that contributes to early development of cardiovascular disease. Impairments in autonomic function markedly impacts blood pressure control [18] and promote the development of cardiac arrhythmias [59-63]. Thus, autonomic dysfunction, relative inactivity and adverse changes in body composition lead to metabolic changes that promote cardiovascular disease in individuals living with SCI. Increasing awareness of these facts has the potential to positively impact individuals and families living with SCI (Figure 1).


This work was supported by National Heart, Lung, and Blood Institute Grant RO1HL-122223
For more Open Access Journals in Juniper Publishers please click on: https://juniperpublishers.com/open-access.php
For more articles in Open Access Journal of Cardiology & Cardiovascular Therapy please click on: https://juniperpublishers.com/jocct/index.php
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2021.09.20 19:50 Alpacccca AFL Supercoach Brownlow 2021

Well, it's a little late, but who cares at this point, it is the 2021 AFL Supercoach Brownlow, brought to you by many hours arranging spreadsheets instead of studying for exams.
Since the official Brownlow medal was last weekend, and we're headed towards the Grand Final, it's as good as time as ever to hold the unofficial Supercoach Brownlow because I didn't have time to run results when the season was over, and still probably don't.
The rules are very similar to the regular Brownlow medal count. The player who scored the most Supercoach points in every game is granted 3 votes, the second most receives two, and the third-highest receives a single vote. All data was collected manually from https://www.fanfooty.com.au/, who has archives of all the stats and scores for each game.
If two or more players scored the same amount of points, the player who had less time on ground was awarded the points, as they had a higher points per minute stat. If they were still even at that point, don't ask because I don't know.
Also, I am very aware of some inconsistencies, but don't know where they went wrong or how to address them.
I'll go over a brief summation of each round, with the full results in the google doc linked: https://docs.google.com/document/d/1IMqUM2aZw-gUfdG4gN7rrKqkDCML68eJ/edit?usp=sharing&ouid=111149946652330442879&rtpof=true&sd=true
Here, I will provide brief commentary as well as a round by round leaderboard showcasing up to 8 players in the top spots at each point in the year. Feel free to skip this section as it is pointless.
Well, this round is really the most uninteresting. Some interesting names are in the lead, like M Flynn (GWS) and J Lever (MEL), with Martin's early domination showing, along with Tex picking up the three as well.
Rank Player Votes
1 T Walker (ADE) 3
J Bowes (GCS) 3
M Flynn (GWS) 3
T Mitchell (HAW) 3
J Lever (MEL) 3
T Boak (POR) 3
D Martin (RIC) 3
C Mills (SYD) 3
B Smith (WBD) 3
Another boring round vote wise. Only 6 players managed to score on both occasions, and in the case of Jordan Ridley and Adam Cerra, two 1 vote games. Coincidentally, both Noah and Jed Anderson polled votes in the North Melbourne vs Gold Coast clash way back when. Tex Walker continued his early dominance, with another 3 vote haul.

Rank Player Votes
1 T Walker (ADE) 6
2 D Martin (RIC) 5
3 E Gulden (SYD) 4
A Brayshaw (FRE) 4
In a flashback to when we had hope that Adelaide might have a miracle rebuild, we see two players in the top 4. Tex polls again, but only one this time and the forseen dominance of ruckmen begins, with Gawn and Grundy springing up into second position. Two 'O's poll in one match, with O'Meara and O'Connor both polling in the otherwise forgettable Geelong Hawthorn clash.

Rank Player Votes
1 T Walker (ADE) 7
2 B Grundy (COL) 6
M Gawn (MEL) 6
4 R Slone (ADE) 5
J Ridley (ESS) 5
D Martin (RIC) 5
Tex freezes in place, as he is leapfrogged by a dominant Gawn in the standings. The top players are beginning to separate themselves from the stragglers, and the most interesting thing that happened here was that 3 games had a 3-2-1 sweep, the most of any round so far.

Rank Player Votes
1 M Gawn (MEL) 8
2 T Walker (ADE) 7
3 B Grundy (COL) 6
J Ridley (ESS) 6
L Parker (SYD) 6
Big Max surges, almost a full two games in front of the 4th placed players with his last 4 weeks totalling a massive 11 votes. Walker is still frozen, and will remain that way until the end of the year. We also see the first appearance of Macrae on the leaderboard, a sight which will remain constant throughout the rest of the year.

Rank Player Votes
1 M Gawn (MEL) 11
2 B Grundy (COL) 8
3 T Walker (ADE) 7
4 J Ridley (ESS) 6
D Mundy (FRE) 6
L Parker (SYD) 6
J Macrae (WBD) 6
Max polls a disappointing 2, allowing Grundy and Macrae to catch up. Mundy keeps rising, and Miller and Ziebell climb up with three vote performances

Rank Player Votes
1 M Gawn (MEL) 13
2 B Grundy (COL) 10
3 J Macrae (WBD) 9
4 D Mundy (FRE) 8
5 T Walker (ADE) 7
T Miller (GCS) 7
J Ziebell (NOR) 7
With four games having all new pollers, not much has changed up top. Walsh has jumped up from just outside the leaderboard, and Guthrie's consistent start to the year is also acknowledged. Grundy has also caught up to Gawn, who fails to poll in their win over North Melbourne.

Rank Player Votes
1 B Grundy (COL) 13
M Gawn (MEL) 13
3 S Walsh (CAR) 9
J Macrae (WBD) 9
5 D Mundy (FRE) 8
C Guthrie (GEE) 8
We have a new leader! But not much else happens. All players in the leaderboard are players who have been here at one stage or another.

Rank Player Votes
1 B Grundy (COL) 15
2 M Gawn (MEL) 13
3 S Walsh (CAR) 9
J Macrae (WBD) 9
5 D Mundy (FRE) 8
C Guthrie (GEE) 8
T Miller (GCS) 8
C Mills (SYD) 8
Shorter leaderboard here because of the abundance of players on 8 votes, but there we see Lyons and Bontempelli join the higher groups with high scoring polling in each of their games.

Rank Player Votes
1 B Grundy (COL) 15
2 M Gawn (MEL) 13
3 C Guthrie (GEE) 11
4 S Walsh (CAR) 9
J Macrae (WBD) 9
Grundy pulls a full game away from Gawn, while more players join up on 11 votes, including some newcomers to the leaderboard. Official Brownlow winner Ollie Wines is nowhere to be found, even on a leaderboard of 15 like seen in the google doc.

Rank Player Votes
1 B Grundy (COL) 17
2 M Gawn (MEL) 14
3 J Lyons (BRI) 11
C Guthrie (GEE) 11
T Miller (GCS) 11
While Miller equals Gawn for second place, Macrae outplays Oliver for the three votes, placing him a single vote above at the halfway point of the season. Parish also joins the leaderboard for the first time this season.
Rank Player Votes
1 B Grundy (COL) 17
2 T Miller (GCS) 14
M Gawn (MEL) 14
4 J Macrae (WBD) 13
5 C Oliver (MEL) 12
6 J Lyons (BRI) 11
D Parish (ESS) 11
C Guthrie (GEE) 11
Well, there is a fairly obvious mistake in these, with Bontempelli somehome gaining 4 votes in one round via the leaderboards, but his standard 3 in the game-by-game totals. Anyways, big movements here, with four players in equal third. Gawn finally wakes up from his dormancy, claiming equal first position once again.

Rank Player Votes
1 B Grundy (COL) 17
M Gawn (MEL) 17
3 D Parish (ESS) 14
T Miller (GCS) 14
M Bontempelli (WBD) 14
J Macrae (WBD) 14
7 J Lyons (BRI) 12
C Oliver (MEL) 12
In the middle of bye weeks, movement is limited in these next two rounds. Gawn retakes top position with his one vote against the Pies, but an unchanged list minus some drop-offs.

Rank Players Voters
1 M Gawn (MEL) 18
2 B Grundy (COL) 17
3 D Parish (ESS) 14
T Miller (GCS) 14
M Bontempelli (WBD) 14
J Macrae (WBD) 14
With only 5 games, very limited options with changes here. However, with the Demons and Magpies bye, the Bont is able to squeeze into the top 2

Rank Players Votes
1 M Gawn (MEL) 18
2 B Grundy (COL) 17
M Bontempelli (WBD) 17
4 J Lyons (BRI) 14
D Parish (ESS) 14
T Miller (GCS) 14
J Macrae (WBD) 14
Well either it's a massive coincidence or both the Bont and Grundy knew about this, as they both played BOG in either of their games, placing them at the top of the leaderboard. Gawn now sits dormant, and will slowly drop from here one out, with Tom Mitchell finally rejoining the leaderboard

Rank Player Votes
1 B Grundy (COL) 20
M Bontempelli (WBD) 20
3 M Gawn (MEL) 18
4 D Parish (ESS) 16
J Macrae (WBD) 16
6 J Lyons (BRI) 14
T Miller (GCS) 14
T Mitchell (HAW) 14
Grundy tops again, and late charger Steele joins the board. Gawn drops to fifth and will continue to fall with a dry patch in these later rounds.

Rank Player Votes
1 B Grundy (COL) 22
2 M Bontempelli (WBD) 20
3 D Parish (ESS) 19
J Macrae (WBD) 19
5 M Gawn (MEL) 18
6 T Miller (GCS) 17
7 J Steele (STK) 16
Well, Macrae keeps coming... 9 votes in 3 games places him in career-best form, and is one of the many reasons why the Bulldogs dominance was so consistent. Walsh rejoins, and Gawn continues to fall. Wines is still unseen. Grundy pulls up again, sitting on a solid 24 votes.

Rankes Player Votes
1 B Grundy (COL) 24
2 T Miller (GCS) 22
M Bontempelli (WBD) 22
4 D Parish (ESS) 19
J Steele (STK) 19
J Macrae (WBD) 19
7 M Gawn (MEL) 18
8 S Walsh 17
Well, it's the pointy end of the season... and the leaderboard is beginning to take shape. Macrae gets another 3, making it 12 from 4 in an unprecedented run. More well known is Steele's run in the second half of the season, wherein the last 4 he has received 8 in the last 4 games.

Rank Player Votes
1 B Grundy (COL) 24
2 T Miller (GCS) 22
J Macrae (WBD) 22
4 D Parish (ESS) 21
J Steele (STK) 21
6 S Walsh (CAR) 20
M Bontempelli (WBD) 20
Macrae is on top. With 15 votes in 5 games, he has a perfect run since the bye rounds. Little to no change has occurred in the top 8 this round.

Rank Player Votes
1 J Macrae (WBD) 25
2 B Grundy (COL) 24
3 T Miller (GCS) 22
4 D Parish (ESS) 21
J Steele (STK) 21
6 S Walsh (CAR) 20
M Bontempelli (WBD) 20
Well the perfect once again continues, but that's getting boring now. 18 votes in 6 games...

Rank Player Votes
1 J Macrae (WBD) 28
2 B Grundy (COL) 24
3 T Miller (GCS) 23
J Steele (STK) 23
5 S Walsh (CAR) 21
D Parish (ESS) 21
7 M Bontempelli (WBD) 20
Another round, another three votes for Jackson Macrae. It's looking insurmountable by this stage. Grundy has fallen outside of the top two, after the injuries throughout the season. Steele and Miller take home three, and Mitchell catapults himself into the top 8.

Rank Player Votes
1 J Macrae (WBD) 31
2 T Miller (GCS) 26
J Steele (STK) 26
4 B Grundy (COL) 24
5 T Mitchell (HAW) 22
6 S Walsh (CAR) 21
D Parish (ESS) 21
8 M Bontempelli (WBD) 20
Well, it's over. Macrae has won it all, with another 3 votes. With 24 votes in 8 games, this was always going to happen.

Rank Player Votes
1 J Macrae (WBD) 34
2 T Miller (GCS) 26
J Steele (STK) 26
4 B Grundy (COL) 24
5 T Mitchell (HAW) 22
6 S Walsh (CAR) 21
D Parish (ESS) 21
Is there even any point anymore? Anyways...

And the winner of the 2021 SuperCoach Brownlow medal with 34 votes is.... JACK MACRAE from the Western Bulldogs!!!!
Honestly, after he took over that top spot, it was over. No one was catching him. Here is the top 20.

1 J Macrae (WBD) 34
2 J Steele (STK) 29
3 T Miller (GCS) 27
4 T Mitchell (HAW) 25
5 B Grundy (COL) 24
6 S Walsh (CAR) 21
D Parish (ESS) 21
M Gawn (MEL) 21
C Oliver (MEL) 21
10 S Darcy (FRE) 20
O Wines (POR) 20
M Bontempelli (WBD) 20
13 Z Merrett (ESS) 18
14 J Lyons (BRI) 17
15 R Laird (ADE) 16
C Guthrie (GEE) 16
C Petracca (MEL) 16
N Naitanui (WCE) 16
19 C Mills (SYD) 13
L Parker (SYD) 13
Overall, there seems to be a more even distribution of votes compared to the official Brownlow, which is obviously due to the randomness of the algorithm than the imperfect minds of the umpire. There were 210 players who received votes in this competition.
Now, the next question is who received the most votes for each team?
Well here are the results: (ties listed in alphabetical by last name)

Adelaide Rory Laird 16
Brisbane Jarryd Lyons 17
Carlton Sam Walsh 21
Collingwood Brodie Grundy 24
Essendon Darcy Parish 21
Fremantle Sean Darcy 20
Geelong Cameron Guthrie 16
Gold Coast Touk Miller 27
Greater Western Sydney Josh Kelly 12
Hawthorn Tom Mitchell 25
Melbourne Max Gawn, Clayton Oliver 21
North Melbourne Jack Ziebell 9
Port Adelaide Ollie Wines 20
Richmond Jack Graham, Jayden Short 6
St Kilda Jack Steele 29
Sydney Callum Mills, Luke Parker 13
West Coast Nic Naitanui 16
Western Bulldogs Jack Macrae 34

Well, which team scored the most votes? Well, I configured that as well...
In order from highest to lowest (with equals decided by average votes per polled player)
Melbourne 87 12 7.25 1
Sydney 87 16 5.4375 12
Western Bulldogs 86 12 7.1667 2
Essendon 78 12 6.5 6
Geelong 78 14 5.5714 9
St Kilda 77 14 5.5 10
Port Adelaide 75 14 5.3571 13
Brisbane 69 11 6.2727 7
Greater Western Sydney 67 15 4.4667 15
Collingwood 64 11 5.8182 8
Fremantle 59 9 6.5556 5
Adelaide 55 8 6.875 3
Gold Coast 55 10 5.5 11
Hawthorn 53 8 6.625 4
Carlton 52 12 4.3333 17
West Coast 50 10 5 14
North Melbourne 48 11 4.3636 16
Richmond 46 15 3.0667 18
And there we have it... This took far too long to make and I'm about to fall asleep so it's probably a good time to call it off here.
Hopefully people enjoyed this different perspective on who the best player in the league was this year, and if people have improvements for next years one (If that happens) that would be much appreciated.
submitted by Alpacccca to AFL [link] [comments]

2021.09.17 01:13 NitroXYZ I couldn't find stats anywhere regarding round by round Brownlow leaders so I made a spreadsheet myself. Here are some stats I found after compiling it.

So one thing I always hoped for as a resource for Brownlow Medal stats was to see a rolling tally where you could easily scroll through and see, for example, "who was leading the count after 5 rounds in 2010". However I couldn't seem to find that information anywhere.
The closest I got was AFL tables listing out which players polled the 3-2-1 votes for each round in a table like this, but there was no rolling tally. Using this information I decided to go through myself and make a spreadsheet of a round by round count for every Brownlow from 1990-2020, the AFL era. In doing so, these were some stats that I found that I feel are worth sharing.
If you guys have any questions related to players leading after X amount of rounds I may be able to answer them in the comments.
I have more stats prepared to share on Brownlow night but for now here is a small collection of some stats that I found interesting.
What are the fewest amount of rounds (excluding R1) where a player was leading the league in Brownlow votes to win the Brownlow?.
  • for players that won the Brownlow that season because the leagues higher vote getter was ineligible.
Year Player Rounds Leading Rounds Total
2012 Sam Mitchell* NA 0
2012 Trent Cotchin* NA 0
2014 Matt Priddis 23 1
1996 James Hird 22 1
2008 Adam Cooney 21-22 2
2006 Adam Goodes 21-22 2
2003 Mark Ricciutio 21-22 2
1997 Robert Harvey* 18-20 3
What are the most amount of rounds (excluding R1) where a player was leading the league in Brownlow votes for a player that didn’t win the Brownlow?.
  • for players that led the league in Brownlow votes that season but were ineligible to receive the award.
Year Player Rounds Leading Rounds Total
2012 Jobe Watson* 6-23 18
2008 Simon Black 2, 4-6, 8-20 17
1996 Corey McKernan* 3, 9-22 15
2014 Gary Ablett 3, 5-18 15
1993 Wayne Schwass 3-17 15
1991 Craig Turley 2, 4-11, 15-18 13
1997 Chris Grant* 4, 6-9, 14-17, 21-22 11
2003 Andrew McLeod 3-7, 9-10, 13-16 11
2019 Patrick Cripps 2-10, 12 10
2006 Scott West 4-5, 11-17, 20 10
What is the record for most consecutive rounds leading the Brownlow Medal Count?.
Year Player Rounds Leading Rounds Total
2009 Gary Ablett 1-22 22
2015 Nat Fyfe 4-23 20
2012 Jobe Watson 6-23 18
1990 Tony Liberatore 6-22 17
2010 Chris Judd 7-22 16
1994 Greg Williams 9-24 16
2020 Lachie Neale 4-18 15
1993 Wayne Schwass 3-17 15
2014 Gary Ablett 5-18 14
1996 Corey McKernan 9-22 14
2004 Chris Judd 10-22 13
2008 Simon Black 8-20 13
1998 Robert Harvey 10-22 13
2016 Patrick Dangerfield 12-23 12
2019 Nat Fyfe 13-23 11
2013 Gary Ablett 10-20 11
What is the record for most Brownlow votes for a player that didn’t poll in the first X rounds?.
Didn't Poll Until Round X: Year Player Team FINAL
2 2020 Lachie Neale BL 31
3 1998 Robert Harvey SK 32
4 2010 Chris Judd CA 30
4 1994 Greg Williams CA 30
5 2017 Tom Mitchell HW 25
5 2013 Steve Johnson GE 25
6 2006 Adam Goodes SY 26
7 2012 Trent Cotchin RI 26
8 2015 Dustin Martin RI 21
9 1998 Mark Ricciuto AD 21
10 1996 Robert Harvey SK 17
11 2002 Des Headland BL 16
12 2007 Adam Goodes SY 20
13 1993 Robert Harvey SK 12
14 1996 Paul Salmon HW 18
15 1994 Tony Francis CW 11
16 2012 David Mundy FR 12
What is the record for most Brownlow votes for a player polled their last votes for the season with X rounds remaining?
Didn't Poll in final X Rounds Year Player Team FINAL
1 2011 Dane Swan CW 34
2 2019 Nat Fyfe FR 33
3 2012 Jobe Watson ES 30
3 2011 Sam Mitchell HW 30
4 2019 Tim Kelly GE 24
5 2014 Patrick Dangerfield AD 21
6 2015 Nat Fyfe FR 31
7 2007 Simon Black BL 22
8 2014 Gary Ablett GC 22
9 2003 Andrew McLeod AD 18
10 2018 Nat Fyfe FR 16
10 1992 Stewart Loewe SK 16
11 2001 Shane OBree CW 12
11 1998 Matthew Burton FR 12
12 1993 Wayne Schwass NM 14
13 1994 Ashley McIntosh WC 11
14 2007 Chris Judd WC 16
15 1992 Brad Tunbridge SY 8
Additional small facts.
  • In 2014 Shane Mumford was leading the league in total Brownlow votes after one round (R3), the same amount of rounds as eventual winner Matt Priddis who was also leading the league in total Brownlow votes after just one round (R23)
  • In 2009 Gary Ablett Jnr was leading the Brownlow Medal Count after every round of the season! He was BOG in round 1, tied with Bryce Gibbs on 5 votes in round 2 and tied with Nic Dal Santo during rounds 3,4,7 and 8 but no player ever had more votes than him after the completion of a round.
  • In 2003 Ben Cousins was leading the Brownlow Medal Count from rounds 17-21, 5 rounds, but failed to win the Brownlow after not leading after round 22. This is the only instant where an eligible player led for at least the last 3 rounds before the final round and failed to win the Brownlow.
Here is a visulisation to help understand, where X signifies that the player was leading the count.
Year Player R17 R18 R19 R20 R21 R22
2003 Ben Cousins X X X X X
2003 Adam Goodes X X X X X
2003 Nathan Buckley X X X X
2003 Mark Ricciutio X X
submitted by NitroXYZ to AFL [link] [comments]

2021.07.27 11:42 BiologyPhDHopeful Frustration post: my entire lab is exhausted & drowning

My fellow main lab members (and myself) have been putting in 60, 70, 80+ hours a week for almost three months straight.
I’m exhausted. They’re exhausted. Our new brilliant PhD student is thinking about quitting. I’m thinking about quitting. Our only post doc is at his witts end.
Meanwhile, my PI hasn’t spent a full week in the lab in at least a year and a half. They are CONSTANTLY on vacation, and CONSTANTLY pushing their grant/review/administrative duties onto us. (Especially me).
I nearly flipped when my PI gave my undergrad 24 hours to finish his research paper (that isn’t due for a week) because… you guessed it, another vacation. Then, pushed off an R21 on me to finish, gave a first year PhD student less than one month to finish a manuscript for actual publication, and made demands to have a full publishable perspective in 2 days.
Mind you, this is the same PI that gave my majorly funded grant to another student 3 weeks before my committee meeting last year, effectively scooping two years of work… along with a bundle of other unethical decisions.
Fuck, it’s so frustrating.
submitted by BiologyPhDHopeful to GradSchool [link] [comments]

2021.05.07 18:12 dem0n0cracy Sugar-sweetened drinks linked to increased risk of colorectal cancer in women under 50, study finds -- The researchers calculated a 16% increase in risk for each 8-ounce serving per day. And from ages 13 to 18, each daily serving was linked to a 32% increase in risk.


Sugar-sweetened drinks linked to increased risk of colorectal cancer in women under 50, study finds

Sugary beverage consumption in adolescence, young adulthood associated with increased risk

Date:May 6, 2021Source:Washington University School of MedicineSummary:Colorectal cancer diagnoses have increased among people under age 50 in recent years and researchers are seeking reasons why. A new study has found a link between drinking sugar-sweetened beverages and an increased risk of developing colorectal cancer in women under age 50. The findings suggest that heavy consumption of sugary drinks during adolescence (ages 13 to 18) and adulthood can increase the disease risk.
Colorectal cancer diagnoses have increased among people under age 50 in recent years and researchers are seeking reasons why. A new study led by Washington University School of Medicine in St. Louis has found a link between drinking sugar-sweetened beverages and an increased risk of developing colorectal cancer in women under age 50. The findings suggest that heavy consumption of sugary drinks during adolescence (ages 13 to 18) and adulthood can increase the disease risk.
The study, published online May 6 in the journal Gut, provides more support for public health efforts that encourage people to reduce the amount of sugar they consume.
"Colorectal cancer in younger adults remains relatively rare, but the fact that the rates have been increasing over the past three decades -- and we don't understand why -- is a major public health concern and a priority in cancer prevention," said senior author Yin Cao, ScD, an associate professor of surgery and of medicine in the Division of Public Health Sciences at Washington University. "Due to the increase in colorectal cancer at younger ages, the average age of colorectal cancer diagnosis has gone down from 72 years to 66 years. These cancers are more advanced at diagnosis and have different characteristics compared with cancers from older populations.
"Our lab is funded by the National Cancer Institute (NCI) and the National Comprehensive Cancer Network to identify risk factors, the molecular landscapes, and precision screening strategies for these cancers so that they can be detected earlier and even prevented," said Cao, who also has a master's of public health. "In past work, we have shown that poor diet quality was associated with increased risk of early-onset colorectal cancer precursors, but we have not previously examined specific nutrients or foods."
Compared with women who drank less than one 8-ounce serving per week of sugar-sweetened beverages, those who drank two or more servings per day had just over twice the risk of developing early-onset colorectal cancer, meaning it was diagnosed before age 50. The researchers calculated a 16% increase in risk for each 8-ounce serving per day. And from ages 13 to 18, an important time for growth and development, each daily serving was linked to a 32% increased risk of eventually developing colorectal cancer before age 50.
Sugar-sweetened drink consumption has been linked to metabolic health problems, such as type 2 diabetes and obesity, including in children. But less is known about whether such high-sugar beverages could have a role in the increasing incidence of colorectal cancer in younger people. Like early-onset colorectal cancer rates, consumption of such drinks has increased over the past 20 years, with the highest consumption level found among adolescents and young adults ages 20 to 34.
The researchers analyzed data from the Nurses' Health Study II, a large population study that tracked the health of nearly 116,500 female nurses from 1991 to 2015. Every four years, participants answered surveys that included questions about diet, including the types and estimated amounts of beverages they drank. Of the total participants, over 41,000 also were asked to recall their beverage habits during their adolescence.
The researchers identified 109 diagnoses of early-onset colorectal cancer among the nearly 116,500 participants.
"Despite the small number of cases, there is still a strong signal to suggest that sugar intake, especially in early life, is playing a role down the road in increasing adulthood colorectal cancer risk before age 50," said Cao, also a research member of Siteman Cancer Center. "This study, combined with our past work linking obesity and metabolic conditions to a higher risk of early-onset colorectal cancer, suggests that metabolic problems, such as insulin resistance, may play an important role in the development of this cancer in younger adults."
With the increasing rates in mind, the American Cancer Society has recently lowered the recommended age for a first screening colonoscopy to 45, down from the previously recommended age 50 for people at average risk. Those with additional risk factors, such as a family history of the disease, should start even earlier, according to the guidelines.
Since the study only included female nurses, most of whom were white, more work is needed to examine this link in people of more diverse races, ethnicities and genders.
While sugar-sweetened beverages were linked to an increased risk of early-onset colorectal cancer, some other drinks -- including milk and coffee -- were associated with a decreased risk. This observational study can't demonstrate that drinking sugary beverages causes this type of cancer or that drinking milk or coffee is protective, but the researchers said that replacing sweetened beverages with unsweetened drinks, such as milk and coffee, is a better choice for long-term health.
"Given this data, we recommend that people avoid sugar-sweetened beverages and instead choose drinks like milk and coffee without sweeteners," Cao said.
Co-authors of the study include Ebunoluwa Otegbeye, MD, a general surgery resident at Washington University working in the Cao lab. Otegbeye is supported by the Surgical Oncology Basic Science and Translational Research Training Program. Collaborators include researchers at the Harvard T.H. Chan School of Public Health and Harvard Medical School.
This work was supported by the National Institutes of Health (NIH), grant numbers U01 CA176726, R01 CA205406, R21 CA230873, R01 CA151993, R35 CA197735, R35 CA253185, R03 CA197879, R21 CA222940, R37 CA246175, K07 CA218377 and T32 CA009621; the Department of Defense, grant number CA160344; the Project P Fund; the Stuart and Suzanne Steele MGH Research Scholarship; and an Investigator Initiated Grant from the American Institute for Cancer Research.
Story Source:
Materials provided by Washington University School of Medicine. Original written by Julia Evangelou Strait. Note: Content may be edited for style and length.
Journal Reference:
  1. Jinhee Hur, Ebunoluwa Otegbeye, Hee-Kyung Joh, Katharina Nimptsch, Kimmie Ng, Shuji Ogino, Jeffrey A Meyerhardt, Andrew T Chan, Walter C Willett, Kana Wu, Edward Giovannucci, Yin Cao. Sugar-sweetened beverage intake in adulthood and adolescence and risk of early-onset colorectal cancer among women. Gut, 2021; gutjnl-2020-323450 DOI: 10.1136/gutjnl-2020-323450
submitted by dem0n0cracy to StopEatingSugar [link] [comments]

2021.04.15 00:20 500scnds [Table] r/AskScience — AMA Series: We are rare disease experts and directors with the NIH, ask us anything!


For proper formatting, please use Old Reddit

The AMA began with the following, fairly lengthy message:
Hello everyone, thank you for joining the Reddit AMA for rare diseases. To start, we’d like to provide the U.S. definition for a rare disease (as defined in the Orphan Drug Act of 1983, and the Rare Disease Act of 2002): In the United States, a rare disease is defined as a disease or condition that affects fewer than 200,000 people in this country. Rare diseases are sometimes called orphan diseases, and we tend to use “rare disease” and “orphan disease” interchangeably.
A few FAQs:
  • Most rare diseases are genetic disorders, typically affecting a single gene.
  • At the current time, there are about 7,000 different rare diseases, each affecting only a few hundred to a few thousand people (sometimes fewer). As we continue to uncover the underlying genetics of more rare diseases, the number of known rare diseases increases by about 200-250 diseases each year.
  • Only about 5% of rare diseases have an FDA-approved treatment. (The FDA estimates about 450-500 drugs and biologics are approved to treat a variety of rare diseases)
  • NIH devoted around $6 billion to rare diseases research in Fiscal Year 2019. This research is very diverse, ranging from basic science to translational science to clinical trials in a broad array of diseases and conditions.
  • The National Center for Advancing Translational Sciences (NCATS) within NIH has identified rare diseases as a priority research area. Some examples of NCATS-supported rare diseases research programs include:
Rare Disease Day at NIH will virtually take place on March 1. Please join us! Registration is open. - Dr. Anne Pariser, NCATS ORDR Director
Rows: ~40
Questions Answers
With COVID-19 cases surging there is an estimate that 10% of severely impacted COVID-19 patients will go onto developing "long covid." Dr. Faucci and Deputy Director Tedros Adhanom have said these people best identify with the Myalgic Encephalomyelitis patients and have expressed concerns that these symptoms could last indefinitely. What are we doing for these people with ME/CFS? We do not yet know how many people will develop ME/CFS following infection by SARS-CoV-2 and we do not have data regarding the effect of the virus on people who have ME/CFS. I have recently started a study that will be following individuals who are recovering from COVID-19 to understand how their symptoms change over time. We will also be recruiting people who have now developed ME/CFS after COVID infection and will compare them to participants in our current ME/CFS protocol. Research on long-term effects of COVID will teach us about diseases with similar symptoms, such as ME/CFS.
The CDC is hosting the Interagency ME/CFS Working Group meeting on Feb. 25-26. The focus on Day 2 of the meeting will be long COVID. For more information about the meeting, please visit: https://www.nih.gov/mecfs/events. - Dr. Avindra Nath, NINDS Clinical Director
How do/can researchers study a disease accurately and thoroughly when there's so much diversity in how every patient expresses the disease and when there might also not be many scientists studying the specific disease too? How quickly can treatments be given to these patients, and what can be done to increase funding and research support? This is an excellent question. Even for a rare disease caused by a well understood genetic misspelling, individuals may have widely different manifestations. An example is a condition that my lab used to research called neurofibromatosis. In that instance individuals in the same family who have the exact same DNA misspelling may be almost without symptoms or severely affected. Obviously care of patients with rare diseases needs to take into account their individual situation and this can’t be done in a formula based approach. This is the whole concept of precision medicine, which is the opposite of one-size-fits-all. Researchers are actively pursuing reasons for these differences in disease presentation. They might be other genetic modifiers or they might be environmental. The more we know about them, the better chance we’ll have to factor them into effective treatment. - Dr. Francis Collins, NIH Director
Most rare diseases have considerable diversity within a disease for symptoms, disease progression, patients affected and many other factors. To best understand a disease, many researchers and patient groups undertake disease registries or natural history studies to better understand the full spectrum of a disease. This can happen in parallel with basic or clinical research. The information obtained in the registry can help in clinical study designs, identifying outcome measures as well as patients for inclusion in trials, among other factors. For patient groups interested in starting and conducting good-quality registries and NHS, additional resources are available through NCATS’ RaDaR program.
The therapy development process varies considerably depending on the disease, candidate therapeutic approaches and how much is known about a disease. NCATS’ mission is to improve the research process so that more treatments can be delivered to more patients more quickly. Some examples of these programs include:
* The Platform Vector Gene Therapy program (PaVe-GT). PaVe GT is a new program whose goal is to try to develop 4 gene therapies for 4 diseases in parallel to try to improve the efficiency of gene therapy development.
* The Rare Diseases Clinical Research Network (RDCRN), where multiple rare diseases are studied at the same time within centers of excellence.
Please visit the NCATS website for more information on some of these programs intended to speed delivery of candidate therapeutics to patients.
- Dr. Anne Pariser, NCATS ORDR Director
Hi all! I recently joined NIH and am very excited for Rare disease day, as I have hypermobile Ehlers-Danlos syndrome (with all of the associated conditions- CFS, POTS, MCAS, etc..) It took me 21 years to get a correct diagnosis. Most of that time was me being blessed with a background in medicine, standing up for myself and not letting my struggles be dismissed by doctors... and having the funds to pay for an innumerable amount of visits. My questions are, what are all of your personal disease group interests? Are you familiar with people’s struggles with doctors - being ignored, gaslighted, told they’re not actually suffering etc? If so, what advice do you have for the medical world, and the patients experiencing this treatment? Also, are you aware of any EDS research being done at NIH? Thank you for your time, and your dedication to rare disease research!! NCATS ORDR, like all of NCATS, is “disease agnostic.” That is, we focus on the research process to try to improve the research environment for all rare diseases, with the goal of bringing more treatments to more patients more quickly. Diagnosis is a difficult and common problem for patients with rare diseases. Because they are rare, many doctors may never have seen a patient with a specific rare disease before, frequently making rare diseases hard to recognize. There are also more than 7,000 different diseases (with more being recognized every day), and it is difficult for doctors to be familiar with each disease and the rapidly changing environment. New strategies to accelerate diagnosis are needed.
To try to help this situation, NCATS has recently published a funding opportunity announcement (FOA) called “Multi-disciplinary Machine-assisted, Genomic Analysis and Clinical Approaches to Shortening the Rare Diseases Diagnostic Odyssey.” This FOA requests applications that combine machine-assisted learning, genomic analysis and clinical approaches that could be adopted by frontline providers to improve and shorten the diagnostic odyssey.
NCATS also runs the GARD information center that includes information on more than 6,500 different rare diseases.
There is ongoing NIH-supported research on EDS. The primary NIH Institute for EDS is the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Additional information can be found on the NIAMS Heritable Disorders of Connective Tissue webpage. You can search for grants to researchers on various topics and disease areas on the NIH RePORTER website. (Type the term of interest into the “TEXT SEARCH” box.)
Additionally, we note that every year hundreds of patients face uncertainty when health care providers are unable to discover the cause for their symptoms. The Undiagnosed Diseases Network (UDN) is a research study backed by the National Institutes of Health Common Fund that seeks to provide answers for patients and families affected by these mysterious conditions.
- Dr. Anne Pariser, NCATS ORDR Director
Hi! First I want to say thank you for doing this! I am signed up for Rare Across America and am attending rare disease day at NIH, so this is a fun bonus! I have idiopathic hypersomnia and there are currently no FDA approved medications for it. What do you think the answer is to advancing clinical research to understand disease and help get them under control? What can we as patients do to help this along? I am part of the CoRDS registry and have participated in every clinical research trial that has come my way, but I'm interested to know if there is more I could be doing. Thank you again! I am sorry to hear of your diagnosis with idiopathic hypersomnia (IH), which is a chronic disorder that results in daytime sleepiness, unrefreshing sleep and difficulty awakening, among other symptoms. A first step for many rare diseases is to better understand the disease course through natural history studies (NHS) and registries, as you are doing.
For patient groups interested in starting and conducting good quality registries and NHS, additional resources are available through NCATS’ RaDaR program.
Another option is to find a patient organization for your disorder, or start a foundation or patient group if one doesn’t exist. Patient advocacy groups (PAGs) or foundations can help you to find and work with other patients and advocates to fully understand the disease, and to work together toward research and care.
The NCATS Toolkit for Patient-Focused Therapy Development (Toolkit) provides a resource that describes the process for starting a patient group.
Joining together with other patients to start to develop a research agenda can help to develop a priority list for next steps in a disease.
Some other suggestions:
* Explore the NCATS Toolkit for more information on the research process and how you can start or support research on your condition.
* Work with larger rare disease organizations to bring attention to rare diseases, and to take part in educational programs to empower patients.
* Meet with the researchers conducting clinical research trials. Ask the researchers how you can contribute to research, such as helping to inform the patient community about ongoing research and research needs, and meeting the research team to help them understand your disease, among others.
* Consider working with researchers and clinicians to hold a scientific meeting to help you develop or organize a scientific agenda.
​ * NCATS and other Institutes/Centers (ICs) at NIH help support scientific conferences through grants. Please see NCATS’ conference grants page for more information.
* The primary NIH IC that works on idiopathic hypersomnia is the National Institute of Neurological Disorders and Stroke (NINDS). Please see their information page for more resources and information - Dr. Anne Pariser, NCATS ORDR Director
How do biases and inequities in healthcare affect the rare disease community in particular? For example, there are issues around access to treatments, but there are also biases that may lead to a delayed or incorrect diagnosis. What has been done to address this? Does the NIH have a role in overcoming these issues? Thank you! It is unfortunately true that our healthcare system is not free of bias. Rare diseases are no exception. Clearly in the United States, there are health inequities that affect certain populations’ access to healthcare. In addition, rare diseases may encounter a version of bias from providers who are simply unfamiliar with the particular condition and are therefore unprepared to offer the optimal clinical recommendations. NIH seeks to make all of its information on rare diseases accessible to patients and providers. NIH also has a major program in health disparities that aims to identify factors that contribute to bias and to test interventions to try to address those inequities. Our most important partners in addressing these problems are patients and their families, so it is a really good thing that the rare disease community is so active in this space.
- Dr. Francis Collins, NIH Director
How do you feel about the ethics of CRISPR editing? Where should the line be, and for what reasons? >CRISPR gene editing is one of the most exciting developments in biomedical research in the last 10 years. It provides an opportunity to correct DNA misspellings that contribute to disease, including rare diseases. Applying this to somatic cells for conditions like Sickle Cell Disease may make it possible to provide a cure. In fact, such trials are already underway for a few diseases. The ethical dilemma relates to the possible use of CRISPR editing of human embryos. The strong consensus of the ethical community, with which I agree, is that heritable changes in the human genome ought not to be undertaken since that would open the door to reengineering ourselves in a circumstance where actual medical need is hard to identify.
>- Dr. Francis Collins, NIH Director
Thanks for the AMA. Given that MG (Myasthenia Gravis) is classed as a rare disease, what are your thoughts on the findings that people are presenting with MG after a Covid19 infection? Would this mean that Covid19 sets certain gene mutations in motion? Or could it be possible that all MG cases are, at the root, driven by viral infections? That is a very good question. The RDCRN has established the MGNet, which studies myasthenia gravis. This multisite consortia would be a good group to reach out to to explore this question. They have been highly interested in the impact of COVID-19 on their patients. - Dr. Anne Pariser, NCATS ORDR Director
My sons were diagnosed with CGD https://rarediseases.org/rare-diseases/chronic-granulomatous-disease/ at ages 16 and 18. What progress is being made with gene based approaches to treating and curing CGD? What are the obstacles? Who is leading these efforts? Thank you for all of your work on rare diseases and for participating in this event. We really, really appreciate it. Thank you for the question. There is research going on at the NIH Clinical Center on CGD, including the laboratories of Dr. John Gallin and Dr. Harry Malech. Dr. Suk See De Ravin in Dr. Malech’s group is working on genetic therapies for CGD.
-Dr. Anne Pariser, NCATS ORDR Director
I have HNPP, ( www.Hnpp.org) It's caused by mutations in the PMP22 gene, it took 9 years to diagnose ( confirmed by blood test) and I still have to ‘educate’ Doctors today about it, any resources you could share on this condition would be appreciated. From my support group I see all ranges of prognosis, not all good as it’s progressive, and it’s hard to know where it’s going, but would be good to know there is research or something going on to challenge this disease. Thank you for your time Edit to add I also was diagnosed with Fibromyalgia/Raynards, ( not so rare) but are some peoples genetics just prone to being hit by the ‘genetic sick stick’? Diagnosis is a difficult problem for rare diseases. Please also see the response to u/HumbertHum which lists a number of resources and programs to try to improve the diagnostic odyssey. HNPP = Hereditary neuropathy with liability to pressure palsies (MedlinePlus and GARD provide more information).
The primary NIH Institute researching HNPP is NINDS. The NINDS hereditary neuropathy page contains more information and resources. - Dr. Anne Pariser, NCATS ORDR Director
Hi, thank you so much for doing this! What do you see as the biggest barriers to developing therapies for these diseases? As a researcher in the basic sciences, my experience has been that there seems to be a considerable amount of applicable research ongoing even for rare diseases in the academic/preclinical world, but that these have not been pursued for development as therapy. Is this a sentiment you would classify as more broadly true, and if so, what are some of the policy steps that you feel can be taken to improve the situation! Again, thanks so much for doing this! Much has been written about the so-called “Valley of Death.” Basic science discoveries can lead to fundamental understandings of the causes of disease, but translating that into clinical benefit is a long and difficult journey. For rare diseases where the commercial benefits of a successful therapy may be insufficient to inspire private sector interest, good ideas about therapy may simply not get pursued. NIH is intensely interested in developing ways to cross this valley. One way is for NIH-supported researchers to push the research agenda further along--essentially de-risking a project which may then be appealing to a private sector partner. This is a lot of what the National Center for Advancing Translational Sciences (NCATS) does. NIH can also work with Food and Drug Administration (FDA) to identify ways to facilitate clinical developments that can utilize a template which has already been approved, so that every project doesn’t have to start from square one. We are doing that right now for gene therapy.
Read more about basic science research at NIH: https://www.nih.gov/news-events/basic-research-digital-media-kit
- Dr. Francis Collins, NIH Director
What is the best way to create a patient support group if one doesn't exist for your rare disease to advocate for funding and research? Joining together with other patients is an important way to support your community and it also can help to start the development of a research agenda for a disease. Here is one resource available through the NCATS Toolkit for Patient-Focused Therapy Development (Toolkit) that describes the process for starting a patient group.- Dr. Anne Pariser, NCATS ORDR Director
Hi, I would like to thank you for all efforts on gene therapy studies. Just a short question: As a father of an adorable, 6-years old girl with CMD, we’re also awaiting the final results of one of the gene therapy studies that continues at NIH. We’ve seen that especially after 2017, there have been very successful results/achievements. How do you see the future of the gene therapies? Specifically about the muscular dystropies... Thank you again. Best Regards and greetings from Istanbul, Turkey. Onur Cakir Thank you for your question. At the present time, gene therapy using adeno-associated virus (AAV) vectors is showing promise for multiple diseases, and has led to some approved therapies. Looking to the future, genome editing is of great interest. Indeed, last year, an NIH grantee, Dr. Jennifer Doudna, and her collaborator, Dr. Emmanuelle Charpentier, were awarded the Nobel Prize in Chemistry for their discovery of the CRISPCas9 system. Part of the interest in genome editing is the possibility that a single gene editor enzyme might be used for multiple diseases, just by changing the sequence of the “guide” RNA for different diseases. Notably, the NIH Common Fund is supporting a large program on somatic genome editing, with a major focus on better ways to deliver genome editors to more cell types, including the muscle. - Dr. Anne Pariser, NCATS ORDR Director
Hi there and thank you for doing this. My two year old grandson has 3MCC and it’s like chasing a ghost. Are there cures for these types of issues? Are there initiatives studying this and if so, who and how? We have a geneticist team in Boston and they are great but there are so many questions with no answers. Thank you, again. 3MCC deficiency = 3-methylcrotonyl CoA carboxylase deficiency, a rare organic acid disorder (https://rarediseases.info.nih.gov/diseases/10954/3-methylcrotonyl-coa-carboxylase-deficiency). We suggest trying to locate a disease expert who is familiar with the treatment of “Organic Acidemias” (OA). OAs are currently being studied at NIH within the Medical Genetics and Metabolic Genetics Branch. You may wish to consider reaching out to them to see if they have available information or resources that may be available to you, or know of other resources closer to where you live.
You also may wish to contact the GARD information center, which may be able to connect you with other researchers or treating clinicians. You may contact a GARD information specialist at 1-888-205-2311, or online.
While there are many promising areas of research into therapies for the treatment of OAs, such as gene therapy, at this time there are no approved therapies specifically for 3-MCCD. However, there are management options for patients, such as low-protein diet and appropriate supplements, that can be overseen by a disease specialist.
-Dr. Anne Pariser, NCATS ORDR Director
Thank you for doing an AMA! How are you all doing today? Has the internet changed how the rare disease community organizes and generates support? Do you think this has had any impact on the development of treatments? Thank you! The internet has opened many doors for rare disease community organizations including: 1. Bringing people together from around the world - it can lessen the isolation that many individuals with rare diseases and their families experience; 2. It provides the ability to share vetted information and best practices; 3. It gives patients and families a voice - they are able to share their experiences with a broad audience, thereby educating people about the rare disease experience; 4. It gives the groups the opportunity to address inaccurate information; 5. It provides the ability to help bring patients together to assist in recruitment efforts for clinical trials.
- Dr. Anne Pariser, NCATS ORDR Director
I am a computer scientist. I work with big data. I have been in awe of things like CRISPR and the general advancement happening in computer aided genetic research. If I was given a chance, I would like to see or build a system that could help the researchers. Although, I have never deeply researched, but always interested. (I apologise for my insincerity) I wanted to know what kind of toolings, computer systems, and analytics goes into detecting, and possibly finding a cure to such diseases. I would love to look up the resources and companies that work in this field that are leveraging modern computation power to tackle this issue. Computation, machine learning, artificial intelligence and other aspects of data science are playing increasingly large roles in biomedical research, given their ability to augment human capacities for aggregation and analysis of the very large amounts of data being produced from basic to translational to clinical research. Resources you could consider are the NIH Office of Data Science Strategy, as well as the recent report from an NIH Advisory Committee to the Director (ACD) Working Group on Data and Informatics. From NCATS, you may find our National COVID Cohort Collaborative (N3C) project and ASPIRE Program particularly interesting, in addition to this story of the citizen-scientist driven Mark2Cure initiative to study rare diseases. - Dr. Chris Austin, NCATS Director
Thank you for hosting this AMA! No field depends more on equitable data sharing than rare diseases, but neither academic researchers nor private institutions (companies) have much incentive to do so. In fact, the opposite is generally true, since keeping data access exclusive ensures a competitive advantage. What can NIH / government do to further promote (enforce?) data sharing by academic and private institutions? Data sharing is critical to all science, and as such NIH has recently announced an important – and more demanding – policy on sharing of data from NIH-supported research. ClinicalTrials.gov is another very important required data-sharing program. Complete, open and prompt sharing of data in an interpretable fashion is particularly critical for NCATS, because translational science is a fundamentally integrative discipline, deriving general insights from the aggregation of many individual translational research efforts. But as with so many other issues in translational science, the methods, standards and operational best practices required to efficiently produce translationally useful new insights from the aggregated data that facile sharing allows have yet to be developed and demonstrated, and are major areas of NCATS innovation. Our open informatics work in drug development (e.g., OpenData Portal) and rare diseases (e.g., GARD), the NCATS-coordinated Rare Diseases Clinical Research Network (RDCRN) Data Management and Coordinating Center, and the unprecedented National COVID Cohort Collaborative program are all examples of NCATS data sharing and dissemination initiatives that are accelerating translational discovery. Watch for my February Director’s Message, which will be posted in the next few days, on just this topic of data sharing! - Dr. Chris Austin, NCATS Director
Thanks for doing this AMA! Given the problems inherent in translating results from one species to another and the ethical concerns with animal research, what is NIH doing to advance non-animal research into rare diseases? Several NIH Institutes and other government agencies have been working to advance non-animal research and animal alternatives for many years; see for example https://www.niehs.nih.gov/research/atniehs/dntp/assoc/niceatm/index.cfm. NCATS has been at the forefront of this work, both in its Tox21 collaboration with NIEHS/NTP, EPA and FDA and in its Tissue Chip for Drug Screening program, which has developed many human cell-based microfluidic bioreactors to mimic human responses to drugs and toxicants, and to model rare diseases and responses to therapeutics. - Dr. Chris Austin, NCATS Director
Do you know of any effective treatments for psoriatic arthritis that aren't immunosuppressive? Research into psychedelics, including psilocybin and LSD, has undergone something of a renaissance in recent years, focusing on their potential use as treatments for a range of neuropsychiatric disorders, including Parkinson’s disease and Alzheimer’s disease. The work is mainly at early clinical stage testing in small numbers of people. - Dr. Chris Austin, NCATS Director
Funding mechanisms for rare disease research? R21, R01? The majority of grants funded at NIH fall under the category of investigator initiated research. Don’t panic if you don’t find a specific funding opportunity announcement (FOA) for the disorder that you are studying. You can use the Research Portfolio Online Reporting Tools to find which part of NIH may be the best fit for your science. NIH program directors at specific institutes or centers can answer your questions regarding the best funding mechanism for your research. NCATS’ Office of Rare Diseases Research can help you navigate NIH to find the right institute and person to contact. Funding opportunity announcements can be found on NCATS’ website.
- Dr. Chris Austin, NCATS Director
the below is another reply to the original question
To jump on this, what are the best current mechanisms for getting basic research into the clinic? Are their ways the current system could be adapted or improved? Rare diseases are always going to be intrinsically difficult to get into the clinic since they are by definition challenging to build a business case for in pharma, so it seems like we’re always going to have to give them some kind of an assist. Thanks for your question. The National Center for Advancing Translational Sciences was created in 2011 precisely to address the first part of your question, which is how to translate basic research into the clinic. For the second part of your question, there is increasing interest in better approaches to develop treatments for rare disease of no commercial interest. These include the NCATS Platform Vector Gene Therapy Program and the Bespoke Gene Therapy Consortium.
More broadly, another approach to more efficient clinical trials is to group rare disease patients according to the underlying disease mechanism, rather than “one disease at a time.” This approach has been valuable in the cancer field. Here are two recent funding announcements: https://grants.nih.gov/grants/guide/rfa-files/RFA-TR-20-031.html and https://grants.nih.gov/grants/guide/rfa-files/RFA-TR-21-010.html. - Dr. Chris Austin, NCATS Director
[deleted] We see and speak with rare disease patients, parents and families almost every day, and study rare diseases on a daily basis. Rare diseases are individually rare (by disease) but collectively they are common. There are about 7,000 different rare diseases, each of which affects a few hundred to a few thousand people (sometimes fewer), which collectively affect an estimated 25-30 million people in the US.
The number and diversity of rare diseases makes it impossible for any one person to be an expert on all rare diseases. However, there are experts and expert centers who focus on clusters of related rare diseases, such as metabolic diseases, bone disease, or rare eye diseases, which allows for expert patient care at these centers. Some examples include the individual rare disease clinical research consortia (RDCRC) within the RDCRN – here is a link to the different RDCRC and the diseases that they study: https://www.rarediseasesnetwork.org/. There are other examples as well, such as Children’s hospitals which often specialize in rare pediatric diseases. Researchers often focus on narrow areas of study for rare diseases as well. For example, there are researchers who exclusively study muscular dystrophy, or specific types of muscular dystrophy and have extensive knowledge within these areas or single diseases.
We recommend that patients and their families try to seek care for a rare disease at an expert center whenever possible. Should you need assistance finding disease experts, please contact the GARD information center who may be able to provide assistance. https://rarediseases.info.nih.gov/
- Dr. Anne Pariser, NCATS ORDR Director
submitted by 500scnds to tabled [link] [comments]

2021.04.04 03:34 TheGiraffeEater Sex Differences in Trait Anxiety's Association with Alcohol Problems in Emerging Adults: The Influence of Symptoms of Depression and Borderline Personality (2019) Journal of substance use, 24(3), 323–328 - https://doi.org/10.1080/14659891.2019.1572800 (US Nat. Library of Medicine National Inst.)

Sex Differences in Trait Anxiety's Association with Alcohol Problems in Emerging Adults: The Influence of Symptoms of Depression and Borderline Personality (2019) Journal of substance use, 24(3), 323–328 - https://doi.org/10.1080/14659891.2019.1572800 (US Nat. Library of Medicine National Inst.)
J Subst Use. Author manuscript; available in PMC 2020 Feb 12.Published in final edited form as:J Subst Use. 2019; 24(3: 323–328.)Published online 2019 Feb 12. doi: 10.1080/14659891.2019.1572800PMCID: PMC6876929NIHMSID: NIHMS1519222PMID: 31768128 Emily A. Atkinson, B.A. and Peter R. Finn, Ph.D.Author information Copyright and License information Disclaimer The publisher's final edited version of this article is available at J Subst Use

Sex Differences in Trait Anxiety’s Association with Alcohol Problems in Emerging Adults: The Influence of Symptoms of Depression and Borderline Personality


Objective: The co-occurrence of alcohol use disorder (AUD) and internalizing psychopathology, such as anxiety and depression, has been well documented. However, most studies of the association between alcohol problems and anxiety, and do not simultaneously consider depression or borderline personality, which covary strongly with both anxiety symptoms and AUDs. The current study examined sex differences in the association between alcohol problems and anxiety, while accounting for depressive and borderline personality (BPD) symptoms. Method: A sample 810 (364 females) young adults aged 18-30 recruited from the community, who varied widely in lifetime alcohol problems, were administered diagnostic interviews and measures of a trait anxiety, depression, and BPD symptoms. Results: Analyses revealed that trait anxiety, depression, and borderline symptoms were all significantly associated with higher lifetime alcohol problems in both males and females. However, the association between trait anxiety and alcohol problems was significantly stronger for males compared with females, even when controlling for depression and BPD symptoms. There were no significant sex differences in the association between alcohol problems and symptoms of either depression or BPD symptoms.
Conclusion: This suggests specific sex differences in the mechanisms by which trait anxiety is associated with alcohol problems.


Alcohol and substance use disorders are associated with elevated levels of anxiety and negative affect in general (Wills, Sandy, Shinar, & Yaeger, 1999). The elevated levels of anxiety observed in those with Alcohol Use Disorders (AUDs) may reflect internalizing psychopathology, such as an anxiety disorder or depression, or may also reflect the negative affect symptomatology characteristic of Borderline Personality Disorder (BPD), which is strongly associated with substance use disorders (Kruedelbach, McCormick, Schulz, & Grueneich, 1993; Trull, Sher, Minks-Brown, Durbin, & Burr, 2000). Internalizing psychopathology has long been acknowledged as a potential factor in the development and perpetuation of alcohol and other substance use disorders (Cowley, 1992; Kendler et al., 1995) and the association between anxiety, in particular, and alcohol problems has been well documented in the literature (Kessler et al., 1997; Lazarus, Beardslee, Pedersen, & Stepp, 2016; Kushner, Krueger, Frye, & Peterson, 2008; Kushner et al., 2012). Much of the previous work focused on the relationship between alcohol problems and internalizing psychopathology conceptualized broadly as a single multifactorial dimension. Previous studies have suggested that increased alcohol problems in high internalizing individuals is related to motivation to use alcohol as a means of tension or stress reduction (Conger, 1956; Sher, 1987) and that internalizing symptoms are a risk factor for development of alcohol problems.
Furthermore, it has also been shown that alcohol use in response to negative emotional states is particularly prevalent in individuals with AUDs and comorbid Borderline Personality Disorder (Stepp, Trull, & Sher, 2005). As Borderline Personality Disorder (BPD) reflects both internalizing and externalizing psychopathology (Eaton et al. 2011, Krueger, Caspi, Moffitt, & Silva, 1998), BPD symptoms are a potential risk factor for the development of AUDs and are, therefore, relevant in studies of the relationship between internalizing psychopathology and alcohol problems. Additionally, while BPD is strongly associated with substance use disorders (Kruedelbach et al., 1993; Trull et al., 2000) and a specific feature of BPD is emotional dysregulation reflected in depressive affect (American Psychiatric Association, 2013), there are few if any studies of the association between AUDs and dimensions of internalizing psychopathology along with BPD symptoms.
The relationship between alcohol problems and negative emotional states associated with depression has also been extensively documented in the literature (Grant & Hartford, 1995, Petty 1992, Swendsen & Merikangas, 2000). Specifically, studies have shown that individuals with an Alcohol Use Disorder and comorbid depression may respond less favorably to treatment and are at an increased risk for suicide compared to individuals with only a depression diagnosis (Davis, Uezato, Newell, & Frazier, 2008). While the directionality of this relationship is not clear, there is evidence suggesting that depression may be a consequence of a primary Alcohol Use Disorder rather than a causal factor (Brown et al., 1995; Dackis, Gold, Pottash, & Sweeney, 1986).
Additionally, Kushner, Abrams, & Borchardt (2000) suggest that anxiety disorders may both lead to, and be a consequence of, AUDs. The literature also proposes that anxiety is likely involved in the maintenance of alcohol problems, where alcohol is ingested in larger amounts for its anxiolytic effects (Kushner et al., 2000). It has also been suggested that internalizing symptoms early in life reflect a vulnerability to alcohol problems in adulthood, particularly in those genetically predisposed to AUDs (Caspi et al., 1997; Hussong, Jones, Stein, Baucom, & Boeding, 2011). Moreover, research has suggested that co-morbid anxiety (specifically generalized anxiety) in females with AUDs leads to worse alcohol treatment outcomes (Farris, Epstein, McCrady, & Hunter-Reel, 2012) and that females high in anxiety sensitivity are more likely to use alcohol as a coping mechanism when compared to males (Stewart, Karp, Pihl, & Peterson,1997; Stewart & Zeitlin, 1995). Multiple studies have also shown a link between social anxiety and vulnerability to alcohol problems in both males and females (Buckner & Turner, 2009; Schry, Maddox, & White, 2016). While some research has examined the relationship between internalizing disorders and AUDs in males, this relationship has been explored much less extensively compared with females. Dawson, Goldstein, Moss, Li & Grant (2010) present data suggesting that males experiencing only internalizing psychopathology (without externalizing problems) use greater quantities of alcohol and have more problems when compared to females. It has also been demonstrated that males are more likely than females to use alcohol or other substances to relieve symptoms of social anxiety disorder (Xu et al., 2012). Previous studies do not separate anxiety, depression, and BPD symptoms in studies investigating sex differences in the relationship between internalizing disorders and alcohol problems. The current study aims to expand and further clarify previous findings by investigating sex differences in the relationship between alcohol problems, trait anxiety, depression, and borderline symptoms in young adults.

Materials and Methods - Participants

Young adults aged 18–30 (n = 810) were recruited through advertisements placed online and around the community in a Midwestern college town (cf., Finn, Gunn, & Gerst, 2015; Finn, Gerst, Lake, & Bogg, 2017). The range of ads/flyers targeted, “daring, rebellious, defiant individuals,” “carefree, adventurous individuals who have led exciting and impulsive lives,” “impulsive individuals,” “heavy drinkers wanted for psychological research,” persons with a “drinking problem,” persons who “got into a lot of trouble as a child,” persons “interested in psychological research,” “quiet, reflective and introspective persons,” and “social drinkers.” This approach has been effective in attracting responses from individuals who vary widely in terms of alcohol use and problems as well as disinhibited traits (Finn et al. 2015, 2017; Gunn, Finn, Endres, Gerst & Spinola, 2013). Additionally, the sample was recruited to have a large proportion of individuals with AUDs. Forty percent (n= 323) of the sample had a lifetime DSM-IV diagnosis of alcohol dependence (178 Men and 145 Women). The sample consisted of 46% females (n = 369) and 54% males (n = 441) with mean age 21.3 years. The ethnicity of the sample was 78% Caucasian, 14% African American, 5% Asian, 2% Hispanic, and 1% Pacific Islander. All respondents were given a telephone screening interview that began with a brief description of the study, followed by a series of questions assessing the study exclusion criteria, current and lifetime alcohol and other drug use, lifetime symptoms of alcohol and other drug abuse and dependence, childhood conduct disorder (CCD), and adult antisocial personality (ASP). Participants were excluded from the study if they (a) were not between 18 and 30 years of age, (b) could not read and speak English, (c) had never consumed alcohol, (d) had less than a sixth grade level of education, (e) reported having suffered from any serious head injuries, or (f) had a history of severe psychological problems. Participants were paid $10 dollars an hour for their time in the lab. Table 1 lists the demographic data and mean values on all measures broken up by sex.


Participants were assessed for lifetime alcohol dependence and problems (40% with a lifetime Alcohol Dependence diagnosis) using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA; Bucholz, Cardoret, & Cloninger, 1994) and diagnostic criteria from the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1994). Diagnoses for this study were made prior to the release of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. The analyses used a measure of lifetime alcohol problems, which were total problem counts for positive responses to all questions in the SSAGA section on Alcohol Use Disorders. Sex was determined using a dichotomous item from the demographic section of the SSAGA which assesses biological sex, rather than gender. Borderline symptoms were assessed using the Structured Clinical Interview for DSM-IV (SCID: First, Gibbon, Spitzer, Williams, & Benjamin, 1997) administered in a questionnaire format. This self-report version of the SCID-II BPD section dichotomizes the items into yes or no questions asking whether a participant endorses these types of traits/behaviors in the past several years. These SCID-II screening questionnaires have shown to be highly and reliably correlated with symptoms counts obtained from diagnostic interview (Ekselius, Lindström, von Knorring, Bodlund, & Kullgren, 1994; Jacobsberg, Perry, & Frances, 1995). Trait anxiety was assessed with the Trait Anxiety Scale of the State Trait Anxiety Inventory (Spielberger, Gorsuch, Lushene, Vagg, & Jacobs, 1983). Symptoms of depression were measured with the Beck Depression Inventory (BDI: Beck, Ward, Mendelson, Mock, & Erbaugh, 1961). All of these measures were part of an extensive assessment battery for a large study of disinhibition and alcohol problems (e.g., Finn et al., 2017; Finn et al., 2015; Gunn et al., 2013).

Data Analysis

Bivariate correlations were compared to assess for sex differences in the relationship between Alcohol Problems and our internalizing variables: Trait Anxiety, Depression, and BPD symptoms. Multiple regressions were used to analyze the data in a sequential manner. First, a multiple regression was used to assess the effects of Trait Anxiety, Sex and their interaction on lifetime Alcohol Problems. Then, in a second multiple regression, the main effects of Depression and BPD symptoms were included in the previous model to assess whether symptoms of Depression and BPD accounted for the association between Trait anxiety and Lifetime Alcohol Problems. Finally, separate follow up multiple regression analyses were conducted to explore whether there were sex differences in the effects of either Depression or BPD symptoms and there interactions on lifetime alcohol problems. All analyses were conducted in IBM SPSS 24 (IBM Corp 2016).

Results - The association between Anxiety, Sex, and Alcohol Problems

Tests of differences between bivariate correlations revealed a significantly stronger association between Tait Anxiety and Lifetime Alcohol Problems in males (r = .249, p = .0001) compared with females (r = .204, p = .0001), z = 2.04, p = .02. Table 2 Lists the bivariate correlations for all study variables. Table 3 lists significance tests for differences in correlations between sexes. A multiple regression analysis assessing the effects of Sex and Trait Anxiety and their interaction on Lifetime Alcohol Problems revealed a significant main effect of Trait Anxiety, R2 = .119, F(1, 805) = 78.3, β = .408, p <0.001, and a significant Sex by Trait Anxiety interaction, F(1, 805) = 7.5, β = −.399 p = .006.
Anxiety, Sex, and Alcohol Problems controlling for depression and BPD symptoms
Additional multiple regression analyses were conducted to determine whether Depression or BPD symptoms accounted for the association between Tait Anxiety and Alcohol Problems and the sex differences in the association between Trait Anxiety and Alcohol Problems. An analysis assessing main effects of Sex, Trait Anxiety, Depression, BPD symptoms, and the Sex by Trait Anxiety interaction on Alcohol Problems revealed that the Sex by Trait Anxiety interaction remained significant when Depression and BPD symptoms were included in the model, R2 = .223, F(1, 798) = 6.28, β = −.345, p = .012. Further multiple regression analyses, assessing main effects of Trait Anxiety, Depression, and BPD symptoms on Alcohol Problems, split by Sex, revealed that Trait Anxiety remained a significant predictor of Alcohol Problems in males, R2 = .227, F(1,433) = 5.26, β = .127, p = .022, but not in females, R2 = .202, F(1,364) = 0.027, β = −.031 p = .602. Figure 1 displays the regression lines for males and females.
Figure 1. Regression lines for males and females for Lifetime Alcohol Problems and Trait Anxiety.

Sex, Depression, BPD symptoms and Alcohol Problems

Follow up multiple regression analyses revealed no sex differences in the association between Lifetime Alcohol Problems and either Depression or BPD. The first model, assessing the main effects of Sex, Depression, and their interaction on Alcohol Problems, revealed a significant main effect of Depression, R2 = .149, F(1,809) = 89.09, β = .424, p < .0001, while the interaction between Sex and Depression was not significant, F(1,809) = 2.852, β = −.107, p = 0.092. The second model, assessing the main effects of Sex, BPD symptoms, and their interaction, on Alcohol Problems, revealed a significant main effect of BPD symptoms, R2 = .169, F(1,799) = 90.55, β = .426, p < .0001, but the interaction between Sex and BPD symptoms was not significant, F(1,799) = 0.757, β = −.048, p = 0.385.


The overarching goal of this study was to expand on previous findings on the association between internalizing psychopathology, specifically trait anxiety, and alcohol problems. We aimed to accomplish this by investigating sex differences in the relationship between trait anxiety and lifetime alcohol problems while controlling for symptoms of depression and BPD symptoms, which are known to be related to both anxiety and alcohol problems. Consistent with previous studies (Kessler et al., 1997; Lazarus et al. 2016; Kushner et al. 2008, 2012), the analyses revealed that trait anxiety was positively associated with alcohol problems in both males and females. However, the association was significantly stronger for males when compared to females. These sex differences were also apparent when controlling for symptoms of depression and BPD. Consistent with previous studies both symptoms of depression and BPD were also associated with alcohol problems (Kruedelbach et al. 1993; Trull et al. 2000; Kendler et al. 1995). Furthermore, when the covariance between symptoms of depression and BPD and trait anxiety was considered, trait anxiety remained strongly associated with alcohol problems in males, but not in females. This indicates that, in our sample, the association between trait anxiety and alcohol problems in females might be explained by depression and BPD symptoms. This suggests that the elevated levels of anxiety seen in females with an AUD is a part of a broader depressive – borderline syndrome, rather than specifically reflecting a unique association between trait anxiety and lifetime alcohol problems. On the other hand, for males, trait anxiety was uniquely associated with alcohol problems even while controlling for depression and borderline symptoms.
While many studies have reported an association between anxiety, internalizing psychopathology, and increased risk for alcohol use disorders (Cowley 1992; Kendler et al., 1995; Kessler et al., 1997) the current study adds to the existing literature by suggesting a different process or mechanism for the association between trait anxiety and alcohol problems in females compared with males. Anxiety may represent a unique vulnerability to alcohol problems in males, while in females elevated trait anxiety may reflect a broader syndrome characterized by elevated symptoms of depression and BPD. Our results cannot be used to infer any etiological role for trait anxiety in males with an AUD, since it is a clear possibility that elevated levels of trait anxiety may be a consequence of drinking problems in males. In addition, long-term problematic alcohol use in females may contribute to a syndrome characterized by elevated levels of trait anxiety, depression, and BPD symptoms. More research is needed to determine the causal role for anxiety, and symptoms of depression and BPD in both males and females. In addition, the observed patterns of association may also be unique to alcohol problems in emerging adults as opposed to older individuals with an AUD.
Studies examining sex differences in internalizing psychopathology in individuals with AUDs may have important implications for treatment. For instance, studies have shown that males tend to be more evasive to seeking treatment and respond less favorably to treatment when compared to females (Jarvis, 1992; John, Alwyn, Hodgson, & Phillips, 2008; Otete, Orton, West, & Fleming, 2015). It is possible that, if males are drinking to relieve symptoms of anxiety, elevated levels of trait anxiety may play a unique role in influencing male’s decreased likelihood to seek and respond favorably to treatment. Additionally, these results are relevant as the study focuses on emerging adults during a critical period in their development in which problems with alcohol and substance use are likely to manifest (Clements 1999). Emerging adulthood has also been shown as a critical brain maturation period in which heavy alcohol use can have detrimental effects on brain development and decision making capacity (Silveri 2012). Further investigation into the mechanisms underlying sex differences, as well as gender differences, in the relationship between AUDs and anxiety and internalizing problems in general could aid in the development of treatments that can be tailored to an individual’s particular etiology.
This study has some limitations that need to be considered when interpreting these results. First, the sample is mostly white, young, or emerging, adults, many of whom are college students. Results cannot be generalized to older individuals with longer sustained AUDs. Although our recruitment strategy yielded a substantial number of participants with an Alcohol Dependence diagnosis, their alcohol dependence is best considered as reflecting an early stage disorder given their relatively young age. Thus, it may be that trait anxiety has a unique role in the development or maintenance of alcohol problems in early stage AUDs when individuals are in the emerging adult developmental stage. Second, the recruitment strategy used in this study is biased insofar as it also selected individuals who are interested in participating in research and who are motivated enough to come into a research laboratory, often on repeated occasions, for testing. It is important to note, however, that the recruitment strategies used in this study have been successful in attracting responses from individuals who vary widely in terms of alcohol use and problems, including many who had a lifetime Alcohol Dependence diagnosis, as well as disinhibited traits (Finn et al. 2015, 2017; Gunn et al., 2013). Third, the only measure of anxiety used was a trait anxiety measure (Spielberger, 1983). While this measure is strongly associated with diagnosable anxiety disorders, it does not provide a comprehensive assessment of the kinds of anxiety problems and symptoms that would be experienced in anxiety disorders, such as Generalized Anxiety Disorder. Fourth, it cannot be determined from our data whether the anxiety predated or postdated the experience of alcohol problems in the sample. Additionally, we did not collect information regarding participant’s current use of psychiatric medications such as antidepressants and anxiolytics. Finally, it is important to note that the elevated symptoms of depression and BPD do not necessarily reflect depressive disorders or Borderline Personality Disorder. Specific diagnoses of Depressive Disorder, Borderline Personality Disorder, or an Anxiety Disorder were not ascertained in this sample.
In summary, these results suggest that there are specific Sex differences in the association between trait anxiety and alcohol problems in emerging adults. The results also suggest that most of the association between trait anxiety and alcohol problems in young females reflects a broader syndrome involving symptoms of depression and BPD. Overall, our results suggest that there are different sex specific mechanisms by which trait anxiety is associated with alcohol problems in young, emerging adults.
Keywords: Trait Anxiety, Depression, Borderline Symptoms, Alcohol Problems, Sex Differences
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2021.01.06 18:28 Charming-Access6796 Masks and Face Coverings for the Lay Public - A Narrative Update

I am seeing a lot of misinformation being passed around ottawa and not just limited to this board relating to covid. People either citing outdated information, stuff thats proven wrong, or just a general misunderstanding usually to back up their own moral justification to keep on doing whatever is convenient to them. Its not ill-intent, for the most part, i believe, but it is causing problems- things are getting worse and there's no end to this pandemic in sight, hospitals are getting overwhelmed and we have freezer trucks full of bodies in ontario. so let's take a step back and review the most recent scientific literature-- its what the good people of Ottawa do- study the shit out of everything. and please, please No More Magical Thinking. Just because you are outdoors and transmission is 60x less likely, it can STILL HAPPEN. the coronavirus does not care, you cannot take it to court and say 'but I was outdoors!'

Transmission Dynamics of Severe Acute Respiratory Syndrome Coronavirus 2 Are More Complex Than Previously Believed

Infection control measures for respiratory diseases traditionally distinguish droplets (large, heavy, and believed to account for transmission within 1 to 2 meters) from aerosols (smaller, lighter, and believed to account for more distant transmission) (7). Precautions aimed at contact and droplet control include surface cleansing, handwashing, physical distancing, and wearing masks if less than 6 feet apart; those aimed at controlling airborne diseases include ventilation and wearing masks if sharing air.
Well-documented examples of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection between persons separated by several meters (8, 9), identification of a potentially viable virus in the air after many hours (10, 11), and detailed case analyses of “superspreader events” (12) lend weight to the hypothesis that airborne spread can occur (13). There is growing evidence to support replacing an oversimplified, droplet-or-aerosol model of disease spread with one that accounts for multiple interacting influences on how the virus travels in and through the air (7, 10, 14–25) (Table 1).
When an infected person speaks, shouts, coughs, or sneezes, the (more or less turbulent) gas cloud emitted can carry many particles of different sizes. Depending on their size, ballistic drops may fall to the ground within seconds, whereas smaller particles, aided by humidity and warmth of the exhaled air, can be carried several meters and linger in the air for extended periods (25). Four key factors influence the transmission of airborne respiratory viruses: ventilation, duration of contact, vocalization, and masking (7).
Severe acute respiratory syndrome coronavirus 2 does not spread uniformly. Many infected persons do not infect anyone else, whereas a small proportion infect many—a phenomenon known as overdispersion (κ statistic) of the reproduction number (27). The κ statistic for COVID-19 has been estimated at 0.1 to 0.45 (20, 21), indicating higher dispersion than in, for example, pandemic influenza (where κ is closer to 1, indicating that infected persons all have similar infectivity) (28). In effect, overdispersion of this magnitude means that about 10% of infectious persons, so-called superspreaders, may be responsible for about 80% of secondary transmissions (21).
Scientists and policymakers initially expressed concern that masks or face coverings could cause risk compensation (the wearer reduces other protective behaviors out of a false sense of security) or increase risk for transmission by acting as fomites (especially if there is increased face touching followed by touching of an environmental surface) (70, 71).
A narrative review summarized evidence that refuted the risk compensation hypothesis in the examples most commonly cited by mask skeptics (cycle helmets, seat belts, and interventions to prevent sexually transmitted diseases) (72). The authors also found no evidence to support the claim that risk compensation occurs with masks or face coverings and identified 3 studies that showed that if a person is wearing a mask, protective behaviors seem to increase in those around them (73–75). A fourth study, from Germany, found no evidence of risk compensation when masks were introduced for the public (76). Video evidence from public settings (for example, stations, parks, and shopping malls) in many countries before and after the introduction of masking policies found that those wearing masks touched their faces significantly less frequently than those not wearing masks (77). A systematic review designed to identify harms from mask wearing found no evidence of risk compensation or increased face touching (71).

Claims of Physiologic Decompensation Are Not Substantiated

We found no empirical evidence to support the claim that medical masks or cloth face coverings interfere with gas exchange to a clinically significant extent in healthy persons at rest. In nurses wearing medical masks through a 12-hour shift, no changes were seen in blood carbon dioxide or oxygen levels; minor changes in carbon dioxide levels were detected after wearing a respirator for 12 hours (88). Another study, on surgeons wearing surgical masks, showed a decrease in blood oxygen levels from 98% to 96% during prolonged surgery—a difference that was statistically significant but not clinically relevant (89).
The hypothesis that masks may cause potentially harmful physiologic changes during exercise (90) has limited empirical support (91), perhaps partly because respirators and medical masks need to comply with standards for maximum airflow resistance. Although clinically minor physiologic changes have sometimes been shown when healthy volunteers do intensive exercise while wearing tightly fitting respirators (68, 92–94), those wearing medical (94, 95) and cloth (96) masks showed no physiologic changes during moderate or intensive exercise.
Although many policies acknowledge that some persons should be exempt from mask wearing (on the assumption that such persons could come to harm), there is no consistency—and little firm evidence—on who should be exempt (Table 4) .

Benefits Must Be Balanced Against Harms and Acceptability

The observational studies summarized earlier (45–47, 63), along with the modeling studies (32–38, 48), suggest that across a range of scenarios the use of masks among the general public is an effective strategy in mitigating transmission of SARS-CoV-2. Even with a limited protective effect, masks can reduce total infections and deaths (especially in relation to presymptomatic transmission) and delay the peak time of the epidemic.
However, mandatory masking is unpopular with some and an infringement (albeit a relatively minor one) of individual freedom. Therefore, it should be restricted to situations where it is likely to be both effective and cost-effective (that is, when faced with a disease that is both prevalent and dangerous). It is not justified if the targeted disease is innocuous or can be prevented by other means that are more effective, more acceptable, less risky, or less expensive.
Coronavirus disease 2019 is not innocuous: It has killed millions of persons around the world (105), produced a cohort of survivors with chronic symptoms and unknown long-term prognosis (106), stretched health systems to (and sometimes beyond) their limits (107), and devastated economies (108). Voluntary masking has been successful in many Asian countries (notably Japan, South Korea, Hong Kong, and Taiwan) but less so in Western countries where the measure was less culturally acceptable (109).
Because of potential airborne transmission, COVID-19 is inherently difficult to contain. As with public masking, the effects and costs of school closures, gathering bans, border closures, quarantine regulations, travel restrictions, working from home, closing restaurants and nonessential shops, physical distancing rules, coughing etiquette, handwashing, and restricting visits to hospitals and nursing homes are difficult to quantify. Moreover, these measures play out differently and have different personal costs depending on the situation. For example, schools need to balance their duty of care to vulnerable pupils and staff with their educational mission and student welfare, which includes meeting the needs of pupils of different ages and abilities and those with (for example) autism and hearing impairments. Masking for only some groups, in some parts of schools and with exceptions granted, may be more appropriate than rigid universal mandates.
Concerns about environmental pollution from mask waste (110, 111) are well founded given that medical masks are made from petrochemicals and are nonbiodegradable. Homemade washable cloth face coverings are more environmentally friendly and may have greater cultural appeal (and hence, better adherence) (66, 109).


This narrative review has summarized a heterogeneous body of evidence on population masking in the context of the COVID-19 pandemic. Evidence that the virus can be airborne (and therefore be inhaled) and that masking policies, when effectively delivered, save lives is now strong. There is no evidence of serious harms from masks and face coverings, although discomfort, communication difficulties, and environmental effects are not insignificant. Psychological effects, which are culturally framed, shape acceptance and adherence.
As masking has become recommended or mandated, there is an urgent research agenda to develop alternatives that are more efficient, more comfortable, more acceptable, less disruptive of normal communication practices, and more environmentally friendly than currently available products.
Until the threat of the pandemic is behind us, we recommend that the public wear masks or face coverings in situations and settings where risk for transmission is high—notably where ventilation is poor, when large numbers of persons are gathered, when some are vocalizing (especially singing or shouting), and when contact is prolonged (7).

edit: tl;dr per request:
scientists say for protection you should wear masks ALL the time whenever you are in public, but ESPECIALLY poorly ventilated or crowded areas. But policy makers don't want to say that because it risks ANY compliance in places like Alabama and Arkansas, which leads to targeted high impact mask enforcing, like inside of stores only etc.-- but isn't Ottawa better than that???? we had this thing at effing 0 for multiple, multiple days just 6 months ago... Can we all just please stop ripping off our masks the instance we step outside a store, cos honestly, some of the air you breathe/in out then does go into / come from the store and other peoples' lungs. Maybe walk away for a minute first at least, please??

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2020.11.29 16:58 throwitaway3xnow777 So here’s a finding that estrogen helps with depression. Makes me question things a lot more.

Has anyone seen this? Is this something we can look into ourselves?
submitted by throwitaway3xnow777 to actual_detrans [link] [comments]

2020.11.27 18:55 AdvancedBuilder SSRI's effect on puberty/growth

Numerous studies like these! have found a negative effect of SSRIS on puberty and normal growth in teens, it also says "this drug may affect growth In teens" on the drug pamphlet. In my case, I took SSRIS during puberty and now at 22 I notice small stature, I'm 5'7, my brother is about 5'10 despite having the same parents and he never took SSRIS. I also notice impeded facial bone growth like low cheekbones and recessed jaw and little facial hair which is causing self esteem issues. Anyone else take SSRIS during puberty?
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2020.11.08 02:55 SaiMoi A nanotech diagnosis and treatment could be coming?

Wanted to share something I learned about recently that's making me mull over my future options. There's a promising endo diagnosis/treatment option involving a nanoparticle/dye that can target exclusively endo cells, show them with high or perfect accuracy on a scan, and then be heated with infrared light to kill the cells. Pretty mind-blowing. Here's more:
They're running trials on macaques this year, to be concluded at the beginning of 2022. I would imagine there'd be another 2+ years of human trials after that -- not certain. Here's the one in progress:
Obviously, one of the biggest wins of this treatment would be its precision and accuracy.
My situation is that an endo specialist agreed it's highly likely I have it, and he wanted to go through with surgery. I've chosen not to follow up, partly because I'm dubious about how much endo material can get missed/left behind for how invasive the procedure is, partly because I'm strongly opposed to the hormonal therapy if I can help it, and partly because my symptoms are "manageable" (ish) (and I'm not interested in pregnancy). But I realize I'm running a risk that my abdominal organs could be compromised by the endo, even in the absence of symptoms.
So now the question I have to ask of myself is, do I put weight in this possible treatment (or another) and keep biding my time, or is this a really dumb risk to take...
Curious how this research sits with others :)
submitted by SaiMoi to endometriosis [link] [comments]

2020.10.15 17:24 OrionAnthracis NIAID F31

Hey all,
I'm a third year PhD student in infectious disease research.
When I started in my lab and expressed interest to my PI about submitting an F31 proposal, she seemed supportive and encouraged the application.
Now I have the data to support the F31 I wanted to submit. I have received an institutional fellowship, and one of the requirements for my fellowship is to apply for external funding. I brought this up to my PI and mentioned the F31, and she rejected the idea, suggesting I apply to a different organization.
Turns out I found out this week that she wants to use my data to support an R21 grant for herself.
I feel kinda betrayed, and at a loss. She has been a very supportive mentor up to this point. She currently has and R01 and R21, both of which expire in 2022, as well as some internal funding from the university.
Any advice would be appreciated.
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