Long-chain omega-3 polyunsaturated fatty acid (LC n-3 PUFA) supplements, rich in eicosapentaenoic acid and/or docosahexaenoic acid, are increasingly being recommended within athletic institutions. However, the wide range of doses, durations and study designs implemented across trials makes it difficult to provide clear recommendations. The importance of study design characteristics in LC n-3 PUFA trials has been detailed in cardiovascular disease research, and these considerations may guide LC n-3 PUFA study design in healthy cohorts. This systematic review examined the quality of studies and study design considerations used in evaluating the evidence for LC n-3 PUFA improving performance in physically trained adults. SCOPUS, PubMed and Web of Science electronic databases were searched to identify studies that supplemented LC n-3 PUFA in physically trained participants. Forty-six (n = 46) studies met inclusion. Most studies used a randomised control design. Risk of bias, assessed using the design-appropriate Cochrane Collaboration tool, revealed that studies had a predominant judgment of ‘some concerns’, ‘high risk’ or ‘moderate risk’ in randomised controlled, randomised crossover or non-randomised studies, respectively. A custom five-point quality assessment scale demonstrated that no study satisfied all recommendations for LC n-3 PUFA study design. This review has highlighted that the disparate range of study designs is likely contributing to the inconclusive state of outcomes pertaining to LC n-3 PUFA as a potential ergogenic aid. Further research must adequately account for the specific LC n-3 PUFA study design considerations, underpinned by a clear hypothesis, to achieve evidence-based dose, duration and composition recommendations for physically trained individuals.

This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.

OBJECTIVES/GOALS: In a familial case where 10 of 17 members inherited EA/LVNC in an autosomal dominant pattern, we discovered a novel, damaging missense variant in the gene KLHL26 that segregates with disease and comprises an altered electrostatic surface profile, likely decoupling the CUL3-interactome. We hypothesize that this KLHL26 variant is etiologic of EA/LVNC. METHODS/STUDY POPULATION: We differentiated a family trio (a heart-healthy daughter and EA/LVNC-affected mother and daughter) of induced pluripotent stem cells into cardiomyocytes (iPSC-CMs) in a blinded manner on three iPSC clones per subject. Using flow cytometry, immunofluorescence, and biomechanical, electrophysiological, and automated contraction methods, we investigated iPSC-CM differentiation efficiency between D10-20, contractility analysis and cell cycle regulation at D20, and sarcomere organization at D60. We further conducted differential analyses following label-free protein and RNA-Seq quantification at D20. Via CRISPR-Cas9 gene editing, we plan to characterize KLHL26 variant-specific iPSC-CM alterations and connect findings to discoveries from patient-specific studies. RESULTS/ANTICIPATED RESULTS: All iPSC lines differentiated into CMs with an increased percentage of cTnT+ cells in the affected daughter line. In comparison to the unaffected, affected iPSC-CMs had fewer contractions per minute and altered calcium transients, mainly a higher amount of total calcium release, faster rate of rise and faster rate of fall. The affected daughter line further had shorter shortening and relaxation times, higher proliferation, lower apoptosis, and a smaller cell surface area per cardiac nucleus. The affected mother line trended in a similar direction to the affected daughter line. There were no gross differences in sarcomere organization between the lines. We also discovered differential expression of candidate proteins such as kinase VRK1 and collagen COL5A1 from proteomic profiling. DISCUSSION/SIGNIFICANCE: These discoveries suggest that EA/LVNC characteristics or pathogenesis may result from decreased contractile ability, altered calcium transients, and cell cycle dysregulation. Through the KLHL26 variant correction and introduction in the daughter lines, we will build upon this understanding to inform exploration of critical clinical targets.

A number of governmental and nongovernmental organizations have made significant efforts to encourage the development of artificial intelligence in line with a series of aspirational concepts such as transparency, interpretability, explainability, and accountability. The difficulty at present, however, is that these concepts exist at a fairly abstract level, whereas in order for them to have the tangible effects desired they need to become more concrete and specific. This article undertakes precisely this process of concretisation, mapping how the different concepts interrelate and what in particular they each require in order to move from being high-level aspirations to detailed and enforceable requirements. We argue that the key concept in this process is accountability, since unless an entity can be held accountable for compliance with the other concepts, and indeed more generally, those concepts cannot do the work required of them. There is a variety of taxonomies of accountability in the literature. However, at the core of each account appears to be a sense of “answerability”; a need to explain or to give an account. It is this ability to call an entity to account which provides the impetus for each of the other concepts and helps us to understand what they must each require.

Transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is possible among symptom-free individuals. Patients are avoiding medically necessary healthcare visits for fear of becoming infected in the healthcare setting. We screened 489 symptom-free healthcare workers for SARS-CoV-2 and found no positive results, strongly suggesting that the prevalence of SARS-CoV-2 was <1%.

Colleges and universities around the world engaged diverse strategies during the COVID-19 pandemic. Baylor University, a community of ˜22,700 individuals, was 1 of the institutions which resumed and sustained operations. The key strategy was establishment of multidisciplinary teams to develop mitigation strategies and priority areas for action. This population-based team approach along with implementation of a “Swiss Cheese” risk mitigation model allowed small clusters to be rapidly addressed through testing, surveillance, tracing, isolation, and quarantine. These efforts were supported by health protocols including face coverings, social distancing, and compliance monitoring. As a result, activities were sustained from August 1 to December 8, 2020. There were 62,970 COVID-19 tests conducted with 1435 people testing positive for a positivity rate of 2.28%. A total of 1670 COVID-19 cases were identified with 235 self-reports. The mean number of tests per week was 3500 with approximately 80 of these positive (11/d). More than 60 student tracers were trained with over 120 personnel available to contact trace, at a ratio of 1 per 400 university members. The successes and lessons learned provide a framework and pathway for similar institutions to mitigate the ongoing impacts of COVID-19 and sustain operations during a global pandemic.

Trypanosomes are blood-borne parasites that can infect a variety of different vertebrates, including animals and humans. This study aims to broaden scientific knowledge about the presence and biodiversity of trypanosomes in Australian bats. Molecular and morphological analysis was performed on 86 blood samples collected from seven different species of microbats in Western Australia. Phylogenetic analysis on 18S rDNA and glycosomal glyceraldehyde phosphate dehydrogenase (gGAPDH) sequences identified Trypanosoma dionisii in five different Australian native species of microbats; Chalinolobus gouldii, Chalinolobus morio, Nyctophilus geoffroyi, Nyctophilus major and Scotorepens balstoni. In addition, two novels, genetically distinct T. dionisii genotypes were detected and named T. dionisii genotype Aus 1 and T. dionisii genotype Aus 2. Genotype Aus 2 was the most prevalent and infected 20.9% (18/86) of bats in the present study, while genotype Aus 1 was less prevalent and was identified in 5.8% (5/86) of Australian bats. Morphological analysis was conducted on trypomastigotes identified in blood films, with morphological parameters consistent with trypanosome species in the subgenus Schizotrypanum. This is the first report of T. dionisii in Australia and in Australian native bats, which further contributes to the global distribution of this cosmopolitan bat trypanosome.

Trifludimoxazin, a new protoporphyrinogen oxidase–inhibiting herbicide, is being evaluated for possible use as a soil-residual active herbicide treatment in cotton for control of small-seeded annual broadleaf weeds. Laboratory and greenhouse studies were conducted to compare vertical mobility and cotton tolerance of trifludimoxazin to flumioxazin and saflufenacil, which are two currently registered protoporphyrinogen oxidase–inhibiting herbicides for use in cotton, in three West Texas soils. Vertical soil mobility of trifludimoxazin was similar to flumioxazin in Acuff loam and Olton loam soils, but was more mobile than flumioxazin in the Amarillo loamy sand soil. The depth of trifludimoxazin movement after a 2.5-cm irrigation event ranged from 2.5 to 5.0 cm in all soils, which would not allow for crop selectivity based on herbicide placement, because ideal cotton seeding depth is from 0.6 to 2.54 cm deep. Greenhouse studies indicated that PRE treatments were more injurious than the 14 d preplant treatment when summarized across soils for the three herbicides (43% and 14% injury, respectively). No differences in visual cotton response or dry weight was observed after trifludimoxazin preplant as compared with the nontreated control within each of the three West Texas soils and was similar to the flumioxazin preplant across soils. On the basis of these results, a use pattern for trifludimoxazin in cotton may be established with the use of a more than 14-d preplant restriction before cotton planting.

The Inaccessible Island Rail Atlantisia rogersi, the world’s smallest extant flightless bird, is endemic to Inaccessible Island, a 14-km2 uninhabited island in the Tristan da Cunha archipelago, central South Atlantic Ocean. Rail populations are notoriously hard to survey and the rugged topography of Inaccessible Island makes a survey particularly challenging. Fortunately, Inaccessible Island Rails are very vocal, because their secretive behaviour means birds are hard to observe in the dense vegetation. We assessed the distribution of rails across Inaccessible Island using playbacks at 350 point-count sites in October–November 2018. Rail calls were heard at 98% of sites and we estimate the rail population to be in the order of 10,300 birds (95% CI 9,100–12,200), based on estimated rail densities in the six main habitats. Historic population estimates were reasonably crude and thus not suitable for inferring population trends, but the population appears to be stable and we recommend the species’ status remains as ‘Vulnerable’. The accidental introduction of alien mammals poses the greatest threat to the survival of the Inaccessible Island Rail and the removal of house mouse Mus musculus and ship rat Rattus rattus from neighbouring Tristan da Cunha Island would greatly reduce the risk of such a catastrophe.

Alien species are a driver of biodiversity loss, with impacts of different aliens on native species varying considerably. Identifying the contributions of alien species to native species declines could help target management efforts. Globally, seabirds breeding on islands have proven to be highly susceptible to alien species. The breeding colonies of the pink-footed shearwater (Ardenna creatopus) are threatened by the negative impacts of alien mammals. We combined breeding monitoring data with a hierarchical model to separate the effects of different alien mammal assemblages on the burrow occupancy and hatching success of the pink-footed shearwater in the Juan Fernández Archipelago, Chile. We show that alien mammals affected the rates of burrow occupancy, but had little effect on hatching success. Rabbits produced the highest negative impacts on burrow occupancy, whereas the effects of other alien mammals were more uncertain. In addition, we found differences in burrow occupancy between islands regardless of their alien mammal assemblages. Managing rabbits will improve the reproductive performance of this shearwater, but research is needed to clarify the mechanisms by which alien mammals affect the shearwaters and to explain why burrow occupancy varies between islands.