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Currently there are few antibacterial dosage regimens established to be safe and effective for sea turtles. Pharmacokinetic evaluation of antibiotics is an essential step in establishing accurate dosage guidelines for a particular species. Metronidazole is an antibiotic that is effective against anaerobic bacteria and some protozoa. For most anaerobic bacteria, the minimum inhibitory concentration (MIC) for metronidazole ranges from 0.25 to 4.0 µg/ml. The MIC values for some Clostridium species are up to 8 µg/ml, and for protozoal agents of trichomoniasis (MIC of 0.05 µg/ml), amebiasis, and giardiasis the MIC ranges from 1 to 50 µg/ml. The objective of this study was to determine the pharmacokinetic parameters after administration of metronidazole to aid in the establishment of species-specific dose guidelines in green ( Chelonia mydas ), loggerhead ( Caretta caretta ), and Kemp's ridley ( Lepidochelys kempii ) sea turtles. After administering metronidazole at a dose of 20 mg/kg orally and IV, the pharmacokinetics were very similar for these three species of sea turtles ( n = 6 for each species). For both oral and IV routes of administration, plasma metronidazole concentrations were maintained above 8 µg/ml for approximately 24 h and above 4 µg/ml for approximately 48 h; however, plasma concentrations of 8 µg/ml were reached within 5 min only for the IV route, versus 8 h for the oral route.

Background: Using the Clinical Audit Research and Evaluation of Motor Neuron Disease (CARE-MND) database and the Scottish Regenerative Neurology Tissue Bank, we aimed to outline the genetic epidemiology and phenotypes of an incident cohort of people with MND (pwMND) to gain a realistic impression of the genetic landscape and genotype-phenotype associations., Methods: Phenotypic markers were identified from the CARE-MND platform. Sequence analysis of 48 genes was undertaken. Variants were classified using a structured evidence-based approach. Samples were also tested for C9orf72 hexanucleotide expansions using repeat-prime PCR methodology., Results: 339 pwMND donated a DNA sample: 44 (13.0%) fulfilled criteria for having a pathogenic variant/repeat expansion, 53.5% of those with a family history of MND and 9.3% of those without. The majority (30 (8.8%)) had a pathogenic C9orf72 repeat expansion, including two with intermediate expansions. Having a C9orf72 expansion was associated with a significantly lower Edinburgh Cognitive and Behavioural ALS Screen ALS-Specific score (p = 0.0005). The known pathogenic SOD1 variant p.(Ile114Thr), frequently observed in the Scottish population, was detected in 9 (2.7%) of total cases but in 17.9% of familial cases. Rare variants were detected in FUS and NEK1. One individual carried both a C9orf72 expansion and SOD1 variant., Conclusions: Our results provide an accurate summary of MND demographics and genetic epidemiology. We recommend early genetic testing of people with cognitive impairment to ensure that C9orf72 carriers are given the best opportunity for informed treatment planning. Scotland is enriched for the SOD1 p.(Ile114Thr) variant and this has significant implications with regards to future genetically-targeted treatments., (© 2024. The Author(s).)

Funding decisions influence where, how, and by whom conservation is pursued globally. In the context of growing calls for more participatory, Indigenous-led, and socially just conservation, we undertook the first empirical investigation of how philanthropic foundations working in marine conservation globally engage communities in grant-making decisions. We paid particular attention to whether and how community engagement practices reinforce or disrupt existing power dynamics. We conducted semistructured remote interviews with 46 individuals from 32 marine conservation foundations to identify how conservation foundations engage communities in setting their priorities and deciding which organizations and projects to fund. We found that community engagement in foundation decision-making was limited in practice. Eleven of the 32 foundations reported some form of community engagement in funding decisions. Two of these foundations empowered communities to shape funding priorities and projects through strong forms of engagement. Many engagement practices were one way, one time, or indirect and confined to certain points in decision-making processes. These weaker practices limited community input and reinforced unequal power relations, which may undermine the legitimacy, equity, and effectiveness of conservation efforts. We suggest that foundations aim for stronger forms of community engagement and reflect on how their grant-making practices affect power relations between foundations and communities., (© 2024 The Authors. Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

Introduction: There is a growing emphasis on proficiency-based progression within surgical training. To enable this, clearly defined metrics for those newly acquired surgical skills are needed. These can be formulated in objective assessment tools. The aim of the present study was to systematically review the literature reporting on available tools for objective assessment of minimally invasive gynecological surgery (simulated) performance and evaluate their reliability and validity., Material and Methods: A systematic search (1989-2022) was conducted in MEDLINE, Embase, PubMed, Web of Science in accordance with PRISMA. The trial was registered with the Prospective Register of Systematic Reviews (PROSPERO) ID: CRD42022376552. Randomized controlled trials, prospective comparative studies, prospective single-group (with pre- and post-training assessment) or consensus studies that reported on the development, validation or usage of assessment tools of surgical performance in minimally invasive gynecological surgery, were included. Three independent assessors assessed study setting and validity evidence according to a contemporary framework of validity, which was adapted from Messick's validity framework. Methodological quality of included studies was assessed using the modified medical education research study quality instrument (MERSQI) checklist. Heterogeneity in data reporting on types of tools, data collection, study design, definition of expertise (novice vs. experts) and statistical values prevented a meaningful meta-analysis., Results: A total of 19 746 titles and abstracts were screened of which 72 articles met the inclusion criteria. A total of 37 different assessment tools were identified of which 13 represented manual global assessment tools, 13 manual procedure-specific assessment tools and 11 automated performance metrices. Only two tools showed substantive evidence of validity. Reliability and validity per tool were provided. No assessment tools showed direct correlation between tool scores and patient related outcomes., Conclusions: Existing objective assessment tools lack evidence on predicting patient outcomes and suffer from limitations in transferability outside of the research environment, particularly for automated performance metrics. Future research should prioritize filling these gaps while integrating advanced technologies like kinematic data and AI for robust, objective surgical skill assessment within gynecological advanced surgical training programs., (© 2024 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Psychological interventions, along with antipsychotic medications, are recommended for adults diagnosed with a psychotic disorder. While initially designed to mitigate positive symptoms, psychological interventions targeting personal recovery were developed and aligned with the recovery framework that many mental health services have adopted. Acceptance and Commitment Therapy (ACT) for psychosis is one such intervention that shows promise when delivered in an individual format. There is preliminary evidence that ACT for psychosis in a group format improves recovery., Objective: This trial aims to evaluate the effectiveness of the "Recovery ACT" group program on personal recovery among adults living with a psychotic disorder., Methods: Our unfunded study is a multiagency, prospective, nonrandomized, waitlist control, single-group trial of the Recovery ACT group program. The program involves 7 weekly group sessions of 90 minutes duration and a 90-minute booster session held 1 month later. We intend to recruit 160 adults living with a psychotic disorder who enroll in a group that is offered as a routine clinical service at participating public mental health services in Melbourne, Victoria, Australia. The 4 assessment time points are 4-6 weeks before the start of the group program, at the start of the group program, at the end of the group program, and at the booster session. There is an optional midgroup assessment and follow-up study. The primary outcome is personal recovery. Secondary outcomes include participants' well-being and psychological flexibility processes. Qualitative data are also collected from participants and facilitators., Results: Recruitment began in September 2019 and is ongoing until 2024, subsequent to a 24-month disruption due to the COVID-19 pandemic. As of the submission of this paper, 93 participants consented to the evaluation, 65 completed T1 measures, and 40 had a complete data set for the proposed analyses., Conclusions: This is the first trial evaluating the effectiveness of the Recovery ACT group program on personal recovery for adults living with a psychotic disorder. Findings will contribute to knowledge about psychosocial interventions for adults living with psychosis. This trial may also serve as an example of a partnership between clinicians and academics that can facilitate the translation of research into practice., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12620000223932; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12620000223932., International Registered Report Identifier (irrid): DERR1-10.2196/49849., (©Marilyn L Cugnetto, Eric M J Morris, Siobain F Bonfield, Jesse Gates, Ilona Morrison, Ellie R Newman, Julia D Nicholls, Lisa M Soares, Megan T Antonucci, Jacinta R Clemente, Claire L M Garratt, Eliot Goldstone, David A Pavone, John Farhall. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 18.03.2024.)

We report the development of BioPhysical and Active Learning Screening (BioPALS); a rapid and versatile hit identification protocol combining AI-powered virtual screening with a GCI-driven biophysical confirmation workflow. Its application to the BRPF1b bromodomain afforded a range of novel micromolar binders with favorable ADMET properties. In addition to the excellent in silico/in vitro confirmation rate demonstrated with BRPF1b, binding kinetics were determined, and binding topologies predicted for all hits. BioPALS is a lean, data-rich, and standardized approach to hit identification applicable to a wide range of biological targets., (© 2024 Wiley‐VCH GmbH.)

Psychedelic fungi have experienced a surge in interest in recent years. Most notably, the fungal secondary metabolite psilocybin has shown tremendous promise in the treatment of various psychiatric disorders. The mushroom species that produce this molecule are poorly understood. Here we sought to examine for the first time, the response of a psilocybin-producing species Psilocybe cubensis to casing (peat moss and vermiculite) and supplementation with gypsum (calcium sulfate dihydrate), two common practices in commercial mushroom cultivation. Mycelial samples of genetically authenticated P. cubensis were used to inoculate popcorn grain bags. The fully colonized bags of popcorn grain (0.15 kg) were transferred to bins of 0.85 kg pasteurized horse manure, with or without 1 cm thick layer of casing and/or 5 % gypsum. Our results indicate that the use of a casing layer significantly increases the biological efficiency (161.5 %), by approximately four fold, in comparison to control (40.5 %), albeit with a slight delay (∼2 days) for obtaining fruiting bodies and a somewhat reduced total tryptamine content (0.85 %) as gauged by High Performance Liquid Chromatography measurements. Supplementation with both casing and gypsum, however, appears to promote maximal yields (896.6 g/kg of dried substrate), with a biological efficiency of 89.6 %, while also maintaining high total tryptamine expressions (0.95 %). These findings, revealing methods for maximizing yield of harvest and expressions of psychoactive tryptamines, may prove useful for both home growers and commercial cultivators of this species, and ultimately support the growth of a robust industry with high quality natural products., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kimberly Foster (KF), Isaac Morrison(IM), Marshall Tyler (MT) reports financial support was provided by former Field Trip Health Inc. and KF and IM are currently supported by Future Wellness., (Copyright © 2023 British Mycological Society. Published by Elsevier Ltd. All rights reserved.)