Translational potential of long-term decreases in mitochondrial lipids in a mouse model of Gulf War Illness

Gulf War Illness (GWI) affects 25% of veterans from the 1990–1991 Gulf War (GW) and is accompanied by damage to the brain regions involved in memory processing. After twenty-five years, the chronic pathobiology of GWI is still unexplained. To address this problem, we examined the long-term consequences of GW exposures in an established GWI mouse model to identify biological processes that are relevant to the chronic symptoms of GWI. Three-month old male C57BL6 mice were exposed for 10 days to GW agents (pyridostigmine bromide and permethrin). Barnes Maze testing conducted at 15- and 16-months post-exposure revealed learning and memory impairment. Immunohistochemical analyses showed astroglia and microglia activation in the hippocampi of exposed mice. Proteomic studies identified perturbation of mitochondria function and metabolomics data showed decreases in the Krebs cycle compounds, lactate, β-hydroxybutyrate and glycerol-3 phosphate in the brains of exposed mice. Lipidomics data showed decreases in fatty acids, acylcarnitines and phospholipids, including cardiolipins in the brains of exposed mice. Pilot biomarker studies showed that plasma from exposed mice and veterans with GWI had increases in odd-chain, and decreases in long-chain, acylcarnitines compared to their respective controls. Very long-chain acylcarnitines were decreased in veterans with GWI compared to controls. These studies suggest that mitochondrial lipid disturbances might be associated with GWI and that further investigation is required to determine its role in the pathophysiology of this illness. Targeting mitochondrial function may provide effective therapies for GWI, and that lipid abnormalities could serve as biomarkers of GWI

Ecological drivers of global gradients in avian dispersal inferred from wing morphology

An organism’s ability to disperse influences many fundamental processes, from speciation and geographical range expansion to community assembly. However, the patterns and underlying drivers of variation in dispersal across species remain unclear, partly because standardised estimates of dispersal ability are rarely available. Here we present a global dataset of avian hand-wing index (HWI), an estimate of wing shape widely adopted as a proxy for dispersal ability in birds. We show that HWI is correlated with geography and ecology across 10,338 (>99%) species, increasing at higher latitudes and with migration, and decreasing with territoriality. After controlling for these effects, the strongest predictor of HWI is temperature variability (seasonality), with secondary effects of diet and habitat type. Finally, we also show that HWI is a strong predictor of geographical range size. Our analyses reveal a prominent latitudinal gradient in HWI shaped by a combination of environmental and behavioural factors, and also provide a global index of avian dispersal ability for use in community ecology, macroecology, and macroevolution

AVONET: Morphological, ecological and geographical data for all birds

Functional traits offer a rich quantitative framework for developing and testing theories in evolutionary biology, ecology and ecosystem science. However, the potential of functional traits to drive theoretical advances and refine models of global change can only be fully realised when species-level information is complete. Here we present the AVONET dataset containing comprehensive functional trait data for all birds, including six ecological variables, 11 continuous morphological traits, and information on range size and location. Raw morphological measurements are presented from 90,020 individuals of 11,009 extant bird species sampled from 181 countries. These data are also summarised as species averages in three taxonomic formats, allowing integration with a global phylogeny, geographical range maps, IUCN Red List data and the eBird citizen science database. The AVONET dataset provides the most detailed picture of continuous trait variation for any major radiation of organisms, offering a global template for testing hypotheses and exploring the evolutionary origins, structure and functioning of biodiversity.Fil: Tobias, Joseph A.. Imperial College London; Reino Unido. University of Oxford; Reino UnidoFil: Sheard, Catherine. University of Oxford; Reino Unido. University of Bristol; Reino UnidoFil: Pigot, Alex L.. University of Oxford; Reino Unido. University College London; Estados UnidosFil: Devenish, Adam J. M.. Imperial College London; Reino UnidoFil: Yang, Jingyi. Imperial College London; Reino UnidoFil: Sayol, Ferran. University College London; Estados UnidosFil: Neate Clegg, Montague H. C.. University of Oxford; Reino Unido. University of Utah; Estados UnidosFil: Alioravainen, Nico. University of Oxford; Reino Unido. Natural Resources Institute Finland; FinlandiaFil: Weeks, Thomas L.. Imperial College London; Reino Unido. Natural History Museum; Reino UnidoFil: Barber, Robert A.. Imperial College London; Reino UnidoFil: Walkden, Patrick A.. Imperial College London; Reino Unido. Natural History Museum; Reino UnidoFil: MacGregor, Hannah E. A.. University of Oxford; Reino Unido. University of Bristol; Reino UnidoFil: Jones, Samuel E. I.. University of Oxford; Reino Unido. University of London; Reino UnidoFil: Vincent, Claire. Organización de Las Naciones Unidas; ArgentinaFil: Phillips, Anna G.. Senckenberg Biodiversity And Climate Research Centre; AlemaniaFil: Marples, Nicola M.. Trinity College; Estados UnidosFil: Montaño Centellas, Flavia A.. Universidad Mayor de San Andrés; Bolivia. University of Florida; Estados UnidosFil: Leandro Silva, Victor. Universidade Federal de Pernambuco; BrasilFil: Claramunt, Santiago. University of Toronto; Canadá. Royal Ontario Museum; CanadáFil: Darski, Bianca. Universidade Federal do Rio Grande do Sul; BrasilFil: Freeman, Benjamin G.. University of British Columbia; CanadáFil: Bregman, Tom P.. University of Oxford; Reino Unido. Future-Fit Foundation; Reino UnidoFil: Cooney, Christopher R.. University Of Sheffield; Reino UnidoFil: Hughes, Emma C.. University Of Sheffield; Reino UnidoFil: Capp, Elliot J. R.. University Of Sheffield; Reino UnidoFil: Varley, Zoë K.. University Of Sheffield; Reino Unido. Natural History Museum; Reino UnidoFil: Friedman, Nicholas R.. Okinawa Institute of Science and Technology Graduate University; JapónFil: Korntheuer, Heiko. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Corrales Vargas, Andrea. Universidad Nacional de Costa Rica; Costa RicaFil: García, Natalia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; Argentin

AVONET: morphological, ecological and geographical data for all birds

Functional traits offer a rich quantitative framework for developing and testing theories in evolutionary biology, ecology and ecosystem science. However, the potential of functional traits to drive theoretical advances and refine models of global change can only be fully realised when species-level information is complete. Here we present the AVONET dataset containing comprehensive functional trait data for all birds, including six ecological variables, 11 continuous morphological traits, and information on range size and location. Raw morphological measurements are presented from 90,020 individuals of 11,009 extant bird species sampled from 181 countries. These data are also summarised as species averages in three taxonomic formats, allowing integration with a global phylogeny, geographical range maps, IUCN Red List data and the eBird citizen science database. The AVONET dataset provides the most detailed picture of continuous trait variation for any major radiation of organisms, offering a global template for testing hypotheses and exploring the evolutionary origins, structure and functioning of biodiversity.Additional co-authors: Samuel E. I. Jones, Claire Vincent, Anna G. Phillips, Nicola M. Marples, Flavia A. Montaño-Centellas, Victor Leandro-Silva, Santiago Claramunt, Bianca Darski, Benjamin G. Freeman, Tom P. Bregman, Christopher R. Cooney, Emma C. Hughes, Elliot J. R. Capp, Zoë K. Varley, Nicholas R. Friedman, Heiko Korntheuer, Andrea Corrales-Vargas, Christopher H. Trisos, Brian C. Weeks, Dagmar M. Hanz, Till Töpfer, Gustavo A. Bravo, Vladimír Remeš, Larissa Nowak, Lincoln S. Carneiro, Amilkar J. Moncada R., Beata Matysioková, Daniel T. Baldassarre, Alejandra Martínez-Salinas, Jared D. Wolfe, Philip M. Chapman, Benjamin G. Daly, Marjorie C. Sorensen, Alexander Neu, Michael A. Ford, Luis Fabio Silveira, David J. Kelly, Nathaniel N. D. Annorbah, Henry S. Pollock, Ada M. Grabowska-Zhang, Jay P. McEntee, Juan Carlos T. Gonzalez, Camila G. Meneses, Marcia C. Muñoz, Luke L. Powell, Gabriel A. Jamie, Thomas J. Matthews, Oscar Johnson, Guilherme R. R. Brito, Kristof Zyskowski, Ross Crates, Michael G. Harvey, Maura Jurado Zevallos, Peter A. Hosner, James M. Maley, F. Gary Stiles, Hevana S. Lima, Kaiya L. Provost, Moses Chibesa, Mmatjie Mashao, Jeffrey T. Howard, Edson Mlamba, Marcus A. H. Chua, Bicheng Li, M. Isabel Gómez, Natalia C. García, Martin Päckert, Jérôme Fuchs, Jarome R. Ali, Elizabeth P. Derryberry, Monica L. Carlson, Rolly C. Urriza, Kristin E. Brzeski, Dewi M. Prawiradilaga, Matt J. Rayner, Eliot T. Miller, Rauri C. K. Bowie, René-Marie Lafontaine, R. Paul Scofield, Yingqiang Lou, Lankani Somarathna, Denis Lepage, Marshall Illif, Eike Lena Neuschulz, Mathias Templin, D. Matthias Dehling, Jacob C. Cooper, Olivier S. G. Pauwels, Kangkuso Analuddin, Jon Fjeldså, Nathalie Seddon, Paul R. Sweet, Fabrice A. J. DeClerck, Luciano N. Naka, Jeffrey D. Brawn, Alexandre Aleixo, Katrin Böhning-Gaese, Carsten Rahbek, Susanne A. Fritz, Gavin H. Thomas, Matthias Schleunin

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

AVONET: morphological, ecological and geographical data for all birds

Functional traits offer a rich quantitative framework for developing and testing theories in evolutionary biology, ecology and ecosystem science. However, the potential of functional traits to drive theoretical advances and refine models of global change can only be fully realised when species‐level information is complete. Here we present the AVONET dataset containing comprehensive functional trait data for all birds, including six ecological variables, 11 continuous morphological traits, and information on range size and location. Raw morphological measurements are presented from 90,020 individuals of 11,009 extant bird species sampled from 181 countries. These data are also summarised as species averages in three taxonomic formats, allowing integration with a global phylogeny, geographical range maps, IUCN Red List data and the eBird citizen science database. The AVONET dataset provides the most detailed picture of continuous trait variation for any major radiation of organisms, offering a global template for testing hypotheses and exploring the evolutionary origins, structure and functioning of biodiversity

A case series to test the acceptability, feasibility and preliminary efficacy of AVATAR therapy in anorexia nervosa

Abstract Background Patients with anorexia nervosa tend to experience an inner “eating disorder” voice. They struggle to recognise and assert their own identity over the illness’s identity and relate to it from a powerless and subordinate position. AVATAR therapy was developed to help patients with psychosis to gain greater power and control over distressing voices. The goal of this study was to test the feasibility, acceptability, safety and preliminary efficacy of an adaptation of AVATAR therapy for anorexia nervosa. Methods Twelve adult patients with anorexia nervosa were recruited. Ten completed an assessment session and between five to seven therapy sessions. The assessment session consisted in the creation of an avatar to represent the “eating disorder”. This was accomplished by manipulating auditory and visual characteristics through a specialist computer software. During the therapy sessions, patients interacted with the avatar to assert their own desires and will. Patients completed baseline, end of intervention and follow-up (4-week) online questionnaires. A non-concurrent multiple baselines single case experimental design (SCED) was used (A1BA2). Feasibility, acceptability, safety and preliminary efficacy of the intervention were assessed. Results The therapy met pre-specified criteria relating to (1) Feasibility: sample recruited within three months; retention rate at the end of the treatment phase = 81.9%; therapy completion rate = 90.1%. (2) Safety: no serious adverse events associated with the intervention. (3) Acceptability: mean ratings = 7.5 (SD = 2.61) out of ten, on a 0–10 scale of acceptability (10 = complete satisfaction). With regards to efficacy, participants reported significantly lower levels of distress associated with the eating disorder voice and higher levels of self-compassion at the end of treatment. No other significant changes were observed in frequency of the eating disorder voice, voice’s characteristics, such as omnipotence and malevolence, eating disorder symptoms and symptoms of anxiety, depression and stress. Patients’ feedback indicated that the therapy had helped with their ability to stand up to the illness, make positive changes around eating, and increase their motivation to recover and self-compassion. Conclusion AVATAR therapy for anorexia nervosa is feasible, acceptable and safe for patients. Larger studies are needed to test clinical efficacy. Trial registration The study was pre-registered on the clinicaltrials.gov registry (https://clinicaltrials.gov/ct2/show/NCT04778423)

Characterizing experiences of non-medical switching to trastuzumab biosimilars using data from internet-based surveys with US-based oncologists and breast cancer patients.

PurposeTo characterize current experiences with communication and decision-making practices when non-medical switching to a biosimilar trastuzumab is proposed or required by cancer center or insurer.MethodsWe developed and launched 60- and 51-item internet surveys to elicit US breast cancer patient and medical oncologist lived experiences with trastuzumab biosimilars and patient information needs and seeking practices. We recruited participants using social media and administered via REDCap in 2020-2021.Results143 breast cancer patients and 33 medical oncologists completed the surveys. 63.9% patients reported having switched to a trastuzumab biosimilar and 40.8% reported receiving no prior notification about switching. 44% of patients reported learning about biosimilars primarily through self-directed learning and 41% wanting more time to discuss with oncologist. None of the oncologists reported that the decision to switch a patient to a biosimilar was initiated by them, but rather more frequently by the insurer (45.2%). About 54.8% reported not receiving any pharmaceutical manufacturer material related to the selected biosimilar. Patients and oncologists diverged in their responses to items regarding patient opportunities to ask questions, adequacy of resources, effectiveness of treatment, patient worry, and magnitude of change.ConclusionThere is a need for tailored and effective patient and oncologist information and education on trastuzumab biosimilars, along with improved healthcare communication regarding switching. The discrepancy between patient-reported experiences and oncologist perceptions of the patient experience, suggests a lack of adequate information that may be a challenge not only to the uptake of trastuzumab biosimilars, but to the patient-oncologist relationship

Online sale of small turtles circumvents public health regulations in the United States.

In the United States (U.S.), pet turtles have been associated with outbreaks of salmonellosis, a serious and sometimes-fatal intestinal illness caused by Salmonella bacteria, with nearly 300,000 people being infected in some years. Children are particularly susceptible because of their propensity to put items, including small turtles, in their mouths. In 1975, a U.S. federal regulation prohibited the sale of turtles <4 inches (101.6 mm) in size, except for the purposes of export, scientific, or educational purposes. This regulation was established to reduce the incidence of salmonellosis, particularly in small children. Previous research has not evaluated the availability of turtles <4 inches in size on websites selling wildlife. We monitored 16 websites in 2021 and quantified listings of small turtles. We determined whether information on Salmonella, the 1975 federal regulation, or related state regulations were provided on the websites and determined legality of sales of small turtles by state regulations. We found that all 16 websites openly advertised and sold turtles <4 inches in size, but only half of these websites provided information about Salmonella and/or the federal regulation. These websites required buyers to confirm that they were not purchasing a turtle as a pet, thereby putting the onus on the consumer to adhere to the regulation. We documented 515 listings of turtles <4 inches in size, including 47 species and one hybrid. Our study has demonstrated that internet sales of small turtles currently represent part of the thriving online pet trade in the U.S. Enforcement of the federal regulation faces jurisdictional challenges in most states. Therefore, we recommend continued public education campaigns by public health agencies in the U.S. to help reduce the risk that pet turtle ownership presents

MedLink: A Mobile Intervention to Address Failure Points in the Treatment of Depression in General Medicine

Major depression is common, and imposes Major depression is common, and imposes a high burden in terms of cost, morbidity, and suffering. Most people with depression are treated in general medicine using antidepressant medication. Outcomes are poor due to failure points across the care system, including patient non-adherence, failure of physicians to optimize the treatment regimens, and lack of patient-physician communication. This study reports on the 4-week pilot deployment of MedLink, a mobile intervention aimed at systemically addressing each of these failure points. A mobile app provides the patient with information and collects data on symptoms and side-effects. A cellularly enabled pill bottle monitors medication adherence. Data from these are provided to the physician and patient to foster communication and medication adjustments. Usability evaluation was generally favorable. Medication adherence rates in this first deployment were high with no patients discontinuing, and 84% of doses taken. Depressive symptom severity was significantly reduced. This study supports the use of a comprehensive, systemic approach to mHealth solutions to enhance processes of care for depression by general medicine physicians