Development and implementation of a self-directed violence prevention training program for correctional behavioral health providers: a clinical trial study protocol.

BACKGROUND: Self-directed violence (SDV) comprises both suicide and self-injury and represents a pressing problem among incarcerated persons. Negative impacts of SDV in correctional settings also extend to behavioral health clinicians (BHCs) (e.g., job turnover). Correctional SDV risk assessment and management standards include staff training as part of the comprehensive approach. The Core Competency Model for Corrections (CCM-C) is a novel, evidence-informed training program for BHCs covering both clinician self-management and clinical care skills. METHODS: This pilot trial is a type 3 hybrid implementation-effectiveness approach. It will employ a wait-list control sequential cross-over design. Participants (N = 50-100) will be BHCs employed by the North Carolina Department of Adult Corrections. Following stratification for years of clinical experience, BHCs will be randomly assigned to (1) a training group that receives CCM-C immediately and (2) a wait-list control receiving CCM-C approximately 6 weeks later. Electronically administrated survey evaluation will occur across baseline and two follow-up (i.e., 2 weeks after each training session) time points. DISCUSSION: The primary outcome is feasibility assessed through collaboration with a Corrections Advisory Panel and feedback from BHCs. Secondary effectiveness outcomes that will be evaluated over time include SDV-related knowledge, attitudes, stigma, and intent to use training content. We will examine a tertiary outcome, namely compassion fatigue. Clinical trial limitations and impacts are discussed. TRIAL REGISTRATION: Clinicaltrials.gov, NCT06359574. This study was registered on 04/05/2024.

Play Your Way to an "A": Helping Students Engage During the Social Isolation of Remote Learning.

One hurdle that educators are presented with is that the classroom is no longer limited to a physical location but rather students and professor can meet via the internet and, before COVID19, distance or remote learning was something that students, by and large, had the option of choosing in which whether to engage. Students had the option to take "online courses", whether those be synchronous remote learning or asynchronous online courses. Indeed, numerous studies have focused on investigating the efficacy of many different approaches to distance and online learning. Unfortunately, COVID 19 mandated a rapid transition to remote learning and with this forced change has come what some students describe as "Zoom Fatigue"[1]. Many students reported feeling exhausted, overwhelmed, and disengaged by the dramatic increase in mandated distance education required by the COVID pandemic. Video conferencing has become the "go to" panacea for education during this time and students are spending unprecedented amounts of time in front of a screen where normally they would be in a classroom. This heretofore singular and unique approach to education coupled with decreased peer-to-peer interaction has caused a problem with student engagement [2]. PROBLEM: Students engagement and performance have decreased during COVID 19 due to forced online learning and lack of peer interaction. HYPOTHESIS: We hypothesize that creating a non-graded, fun, and relaxing physiology-focused trivia night will increase student engagement and performance on summative assessments. PROPOSAL: Introduce a voluntary "Trivia Night" review session to increase interaction amongst peers and review respiratory physiology material.

Bulk synthesis and beyond: The roles of eukaryotic replicative DNA polymerases.

An organism's genomic DNA must be accurately duplicated during each cell cycle. DNA synthesis is catalysed by DNA polymerase enzymes, which extend nucleotide polymers in a 5' to 3' direction. This inherent directionality necessitates that one strand is synthesised forwards (leading), while the other is synthesised backwards discontinuously (lagging) to couple synthesis to the unwinding of duplex DNA. Eukaryotic cells possess many diverse polymerases that coordinate to replicate DNA, with the three main replicative polymerases being Pol α, Pol δ and Pol ε. Studies conducted in yeasts and human cells utilising mutant polymerases that incorporate molecular signatures into nascent DNA implicate Pol ε in leading strand synthesis and Pol α and Pol δ in lagging strand replication. Recent structural insights have revealed how the spatial organization of these enzymes around the core helicase facilitates their strand-specific roles. However, various challenging situations during replication require flexibility in the usage of these enzymes, such as during replication initiation or encounters with replication-blocking adducts. This review summarises the roles of the replicative polymerases in bulk DNA replication and explores their flexible and dynamic deployment to complete genome replication. We also examine how polymerase usage patterns can inform our understanding of global replication dynamics by revealing replication fork directionality to identify regions of replication initiation and termination.

Environmental challenges facing athletes, stakeholders and spectators at Paris 2024 Olympic and Paralympic Games: an evidence-based review of mitigation strategies and recommendations.

The upcoming Paris 2024 Olympic and Paralympic Games could face environmental challenges related to heat, air quality and water quality. These challenges will pose potential threats to athletes and impact thousands of stakeholders and millions of spectators. Recognising the multifaceted nature of these challenges, a range of strategies will be essential for mitigating adverse effects on participants, stakeholders and spectators alike. From personalised interventions for athletes and attendees to comprehensive measures implemented by organisers, a holistic approach is crucial to address these challenges and the possible interplay of heat, air and water quality factors during the event. This evidence-based review highlights various environmental challenges anticipated at Paris 2024, offering strategies applicable to athletes, stakeholders and spectators. Additionally, it provides recommendations for Local Organising Committees and the International Olympic Committee that may be applicable to future Games. In summary, the review offers solutions for consideration by the stakeholders responsible for and affected by the anticipated environmental challenges at Paris 2024.

Substrate-induced strain in molybdenum disulfide grown by aerosol-assisted chemical vapor deposition.

Transition metal dichalcogenides have been extensively studied in recent years because of their fascinating optical, electrical, and catalytic properties. However, low-cost, scalable production remains a challenge. Aerosol-assisted chemical vapor deposition (AACVD) provides a new method for scalable thin film growth. In this study, we demonstrate the growth of molybdenum disulfide (MoS2) thin films using AACVD method. This method proves its suitability for low-temperature growth of MoS2thin films on various substrates, such as glass, silicon dioxide, quartz, silicon, hexagonal boron nitride, and highly ordered pyrolytic graphite. The as-grown MoS2shows evidence of substrate-induced strain. The type of strain and the morphology of the as-grown MoS2highly depend on the growth substrate's surface roughness, crystallinity, and chemical reactivity. Moreover, the as-grown MoS2shows the presence of both direct and indirect band gaps, suitable for exploitation in future electronics and optoelectronics.

Remarkable stability of γ - N 2 and its prevalence in the nitrogen phase diagram.

Solid nitrogen exhibits a panoply of phenomena ranging from complex molecular crystalline configurations to polymerization and closing band gap at higher densities. Among the elemental molecular solids, nitrogen stands apart for having phases, which can only be stabilized following particular pressure-temperature pathways, indicative of metastability and kinetic barriers. Here, through the combination of Raman spectroscopy and dynamic compression techniques, we find that the appearance of the whole nitrogen phase diagram is determined by the P-T paths taken below 2 GPa. We reveal the existence of the path- and phase-dependent triple point between the ß - N 2 , δ loc - N 2 and γ - or ϵ - N 2 . We further show that the ß - N 2 towards γ - N 2 path below the triple point, that evades δ ( δ loc )- N 2 , results in the formation of γ - N 2 , which in turn becomes a dominant phase. We then demonstrate, that the ß - N 2 through δ ( δ loc )- N 2 above the triple point path leads to the formation of ϵ - N 2 and the "well-established" phase diagram. An additional pathway, which by-passes the rotationally inhibited modifications δ ( δ loc )- N 2 , via rapid compression is found to produce γ - N 2 at higher temperatures. We argue that the pathway and phase sensitive triple point and the compression rate dependent phase formation challenge our understanding of this archetypal dense molecular solid.

Histopathological characterization and grading of chronic enterocolitis in Sulawesi crested macaques (Macaca nigra).

Sulawesi crested macaques (Macaca nigra) (SCMs) are critically endangered and frequently suffer from chronic intestinal disease in captivity. Often, despite routine diagnostic investigations and confirmation of intestinal inflammation, an aetiology cannot be identified, leading to a non-specific categorization as chronic enterocolitis rather than an aetiological diagnosis. This study evaluates the histological features of gastrointestinal tissues from 23 SCMs, comparing animals with a clinical history suggestive of chronic enterocolitis (n = 14) with those without gastrointestinal clinical signs (n = 9). Tissues were graded according to the Nancy index (NI), a scoring system used in human medicine to evaluate disease activity in ulcerative colitis, a common form of human inflammatory bowel disease (IBD). Additionally, inflammatory cells in the colonic lamina propria were visually identified by type, counted and subsequently compared between diseased and control animals. Moderate to severe lymphoplasmacytic inflammation and structural changes were most common in the colons of affected SCMs, whereas histopathological changes were absent or mild in all examined small intestine (n = 17) and stomach (n = 11) tissues. The colonic NI had a significant positive correlation with clinical disease severity and 57% (n = 8) of animals with clinical signs had a NI grade of ≥2, consistent with moderate to severe, active IBD. Half of SCMs with recurrent rectal prolapse (n = 6) had a NI grade of 0, suggesting that intestinal inflammation is not always part of this condition's pathogenesis. The numbers of colonic lymphocytes, plasma cells, neutrophils, macrophages and total leucocytes were significantly higher in diseased animals. This study validated the use of the NI in SCMs, enabling a more standardized histopathological evaluation of the colon in this species.

The oligomeric states of dye-decolorizing peroxidases from Streptomyces lividans and their implications for mechanism of substrate oxidation.

A common evolutionary mechanism in biology to drive function is protein oligomerization. In prokaryotes, the symmetrical assembly of repeating protein units to form homomers is widespread, yet consideration in vitro of whether such assemblies have functional or mechanistic consequences is often overlooked. Dye-decolorizing peroxidases (DyPs) are one such example, where their dimeric α + ß barrel units can form various oligomeric states, but the oligomer influence, if any, on mechanism and function has received little attention. In this work, we have explored the oligomeric state of three DyPs found in Streptomyces lividans, each with very different mechanistic behaviors in their reactions with hydrogen peroxide and organic substrates. Using analytical ultracentrifugation, we reveal that except for one of the A-type DyPs where only a single sedimenting species is detected, oligomer states ranging from homodimers to dodecamers are prevalent in solution. Using cryo-EM on preparations of the B-type DyP, we determined a 3.02 Å resolution structure of a hexamer assembly that corresponds to the dominant oligomeric state in solution as determined by analytical ultracentrifugation. Furthermore, cryo-EM data detected sub-populations of higher-order oligomers, with one of these formed by an arrangement of two B-type DyP hexamers to give a dodecamer assembly. Our solution and structural insights of these oligomer states provide a new framework to consider previous mechanistic studies of these DyP members and are discussed in terms of long-range electron transfer for substrate oxidation and in the "storage" of oxidizable equivalents on the heme until a two-electron donor is available.

Rapid Peptide Cyclization Inspired by the Modular Logic of Nonribosomal Peptide Synthetases.

Nonribosomal cyclic peptides (NRcPs) are structurally complex natural products and a vital pool of therapeutics, particularly antibiotics. Their structural diversity arises from the ability of the multidomain enzyme assembly lines, nonribosomal peptide synthetases (NRPSs), to utilize bespoke nonproteinogenic amino acids, modify the linear peptide during elongation, and catalyze an array of cyclization modes, e.g., head to tail, side chain to tail. The study and drug development of NRcPs are often limited by a lack of easy synthetic access to NRcPs and their analogues, with selective macrolactamization being a major bottleneck. Herein, we report a generally applicable chemical macrocyclization method of unprecedented speed and selectivity. Inspired by biosynthetic cyclization, it combines the deprotected linear biosynthetic precursor peptide sequence with a highly reactive C-terminus to produce NRcPs and analogues in minutes. The method was applied to several NRcPs of varying sequences, ring sizes, and cyclization modes including rufomycin, colistin, and gramicidin S with comparable success. We thus demonstrate that the linear order of modules in NRPS enzymes that determines peptide sequence encodes the key structural information to produce peptides conformationally biased toward macrocyclization. To fully exploit this conformational bias synthetically, a highly reactive C-terminal acyl azide is also required, alongside carefully balanced pH and solvent conditions. This allows for consistent, facile cyclization of exceptional speed, selectivity, and atom efficiency. This exciting macrolactamization method represents a new enabling technology for the biosynthetic study of NRcPs and their development as therapeutics.

Management Approaches in WHO Grade III Meningioma: A National Oncology Trainees' Collaborative for Healthcare Research (NOTCH) UK Multi-Centre Retrospective Study.

AIMS: WHO Grade 3 (G3) meningiomas are rare tumours with limited data to guide management. This retrospective study documents UK management approaches across 14 centres over 11 years. MATERIALS AND METHODS: Patients with WHO G3 meningioma between 01/01/2008 and 31/12/2018 were identified. Data were collected on demographics, management strategy, adjuvant radiotherapy, approach in recurrence setting and survival. RESULTS: 84 patients were identified. 21.4% transformed from lower-grade disease. 96.4% underwent primary surgical resection, with 20.8% having evidence of residual disease on their post-op MRI. 59.3% of patients underwent adjuvant radiotherapy (RT) following surgical resection. Overall median PFS and OS were 12.6 months and 28.2 months, respectively. Median OS in the group who underwent complete surgical resection was 34.9 months, compared to 27.5 months for those who had incomplete resection (HR 0.58, 95% CI 0.27-1.23, p = 0.15). Median OS was 33.1 months for those who underwent adjuvant RT and 14.0 months for those who did not (HR 0.48, 95% CI 0.27-0.84, p = 0.004). Median adjuvant RT dose delivered was 60Gy (range 12Gy-60Gy), 45.8% of adjuvant RT was delivered using IMRT. At disease relapse, 31% underwent salvage surgery and 29.3% underwent salvage RT. Of those treated with salvage RT, 64.7% were re-treats and all were treated with hypofractionated RT. CONCLUSION: Surgery continues to be the preferred primary management strategy. Post-operative MRI within 48 hours is indicated to assess presence of residual disease and guide further surgical options. Adjuvant radiotherapy plays an important part of the management paradigm in these patients with the data supporting an attached survival advantage. Further surgery and re-irradiation is an option in the disease recurrence setting with radiosurgery frequently utilised in this context.

Characterising 24-h skeletal muscle gene expression alongside metabolic & endocrine responses under diurnal conditions.

CONTEXT: Skeletal muscle plays a central role in the storage, synthesis, and breakdown of nutrients, yet little research has explored temporal responses of this human tissue, especially with concurrent measures of systemic biomarkers of metabolism. OBJECTIVE: To characterise temporal profiles in skeletal muscle expression of genes involved in carbohydrate metabolism, lipid metabolism, circadian clocks, and autophagy and descriptively relate them to systemic metabolites and hormones during a controlled laboratory protocol. METHODS: Ten healthy adults (9M/1F, mean ± SD: age: 30 ± 10 y; BMI: 24.1 ± 2.7 kg·m-2) rested in the laboratory for 37 hours with all data collected during the final 24 hours of this period (i.e., 0800-0800 h). Participants ingested hourly isocaloric liquid meal replacements alongside appetite assessments during waking before a sleep opportunity from 2200-0700 h. Blood samples were collected hourly for endocrine and metabolite analyses, with muscle biopsies occurring every 4 h from 1200 h to 0800 h the following day to quantify gene expression. RESULTS: Plasma insulin displayed diurnal rhythmicity peaking at 1804 h. Expression of skeletal muscle genes involved in carbohydrate metabolism (Name - Acrophase; GLUT4 - 1440 h; PPARGC1A -1613 h; HK2 - 1824 h) and lipid metabolism (FABP3 - 1237 h; PDK4 - 0530 h; CPT1B - 1258 h) displayed 24 h rhythmicity that reflected the temporal rhythm of insulin. Equally, circulating glucose (0019 h), NEFA (0456 h), glycerol (0432 h), triglyceride (2314 h), urea (0046 h), CTX (0507 h) and cortisol concentrations (2250 h) also all displayed diurnal rhythmicity. CONCLUSION: Diurnal rhythms were present in human skeletal muscle gene expression as well systemic metabolites and hormones under controlled diurnal conditions. The temporal patterns of genes relating to carbohydrate and lipid metabolism alongside circulating insulin are consistent with diurnal rhythms being driven in part by the diurnal influence of cyclic feeding and fasting.

Daily quetiapine after severe TBI improves learning and memory.

BACKGROUND: Traumatic brain injury (TBI) induces cognitive deficits driven by neuroinflammation and cerebral edema. The commonly used atypical antipsychotic, quetiapine (QTP), has been recently shown to improve post-TBI outcomes. We hypothesized that QTP would thereby improve animal learning and memory 2 weeks after severe TBI. METHODS: CD1 male mice (n = 35) underwent severe TBI (controlled cortical impact, injury, I) or sham craniotomy (S), followed by BID saline (P, placebo) or QTP (10 or 20 mg/kg, IP) for 2 weeks. Animals underwent Morris Water Maze (MWM) exercises to gauge spatial learning and memory. The distance and time required for swimming animals to reach the platform area (Zone 5, Z5) located in quadrant 1 (Zone 1, Z1) was calculated from digital video recordings analyzed using Ethovision software. Animal bodyweights were recorded daily and on day 14, injured cerebral hemispheres were procured for edema determination (wet-to-dry ratio). Intergroup differences were evaluated with ANOVA/Bonferroni correction (p < 0.05). RESULTS: On day 14, animal weight loss recovery was lowest in I + P compared to I + QTP20 and I + QTP10 (p ≤ 0.01 for either). Cerebral edema was greatest in I + P, and only significantly decreased in I + QTP20 (p < 0.05). Both QTP doses similarly improved spatial learning by significantly reducing latency time and travel distance to target zones (p < 0.05). In probe memory trials, only I + QTP20 and not I + QTP10 significantly favored animal reaching or crossing into target zones (p < 0.05). CONCLUSION: Post-TBI QTP reduces brain edema and improves spatial learning and memory with a potential dose dependence impact benefiting memory up to 14 days. These data suggest an unanticipated QTP benefit following brain injury that should be specifically explored.

Feasible Route to High-Temperature Ambient-Pressure Hydride Superconductivity.

A key challenge in materials discovery is to find high-temperature superconductors. Hydrogen and hydride materials have long been considered promising materials displaying conventional phonon-mediated superconductivity. However, the high pressures required to stabilize these materials have restricted their application. Here, we present results from high-throughput computation, considering a wide range of high-symmetry ternary hydrides from across the periodic table at ambient pressure. This large composition space is then reduced by considering thermodynamic, dynamic, and magnetic stability before direct estimations of the superconducting critical temperature. This approach has revealed a metastable ambient-pressure hydride superconductor, Mg_{2}IrH_{6}, with a predicted critical temperature of 160 K, comparable to the highest temperature superconducting cuprates. We propose a synthesis route via a structurally related insulator, Mg_{2}IrH_{7}, which is thermodynamically stable above 15 GPa, and discuss the potential challenges in doing so.

Neonicotinoid exposure increases Varroa destructor (Mesostigmata: Varroidae) mite parasitism severity in honey bee colonies and is not mitigated by increased colony genetic diversity.

Agrochemical exposure is a major contributor to ecological declines worldwide, including the loss of crucial pollinator species. In addition to direct toxicity, field-relevant doses of pesticides can increase species' vulnerabilities to other stressors, including parasites. Experimental field demonstrations of potential interactive effects of pesticides and additional stressors are rare, as are tests of mechanisms via which pollinators tolerate pesticides. Here, we controlled honey bee colony exposure to field-relevant concentrations of 2 neonicotinoid insecticides (clothianidin and thiamethoxam) in pollen and simultaneously manipulated intracolony genetic heterogeneity. We showed that exposure increased rates of Varroa destructor (Anderson and Trueman) parasitism and that while increased genetic heterogeneity overall improved survivability, it did not reduce the negative effect size of neonicotinoid exposure. This study is, to our knowledge, the first experimental field demonstration of how neonicotinoid exposure can increase V. destructor populations in honey bees and also demonstrates that colony genetic diversity cannot mitigate the effects of neonicotinoid pesticides.

Faster-growing parasites threaten host populations via patch-level population dynamics and higher virulence; a case study in Varroa mites (Mesostigmata: Varroidae) and honey bees (Hymenoptera: Apidae).

Honey bee parasites remain a critical challenge to management and conservation. Because managed honey bees are maintained in colonies kept in apiaries across landscapes, the study of honey bee parasites allows the investigation of spatial principles in parasite ecology and evolution. We used a controlled field experiment to study the relationship between population growth rate and virulence (colony survival) of the parasite Varroa destructor (Anderson and Trueman). We used a nested design of 10 patches (apiaries) of 14 colonies to examine the spatial scale at which Varroa population growth matters for colony survival. We tracked Varroa population size and colony survival across a full year and found that Varroa populations that grow faster in their host colonies during the spring and summer led to larger Varroa populations across the whole apiary (patch) and higher rates of neighboring colony loss. Crucially, this increased colony loss risk manifested at the patch scale, with mortality risk being related to spatial adjacency to colonies with fast-growing Varroa strains rather than with Varroa growth rate in the colony itself. Thus, within-colony population growth predicts whole-apiary virulence, demonstrating the need to consider multiple scales when investigating parasite growth-virulence relationships.

Relative impacts of Varroa destructor (Mesostigmata:Varroidae) infestation and pesticide exposure on honey bee colony health and survival in a high-intensity corn and soybean producing region in northern Iowa.

The negative effects of Varroa and pesticides on colony health and survival are among the most important concerns to beekeepers. To compare the relative contribution of Varroa, pesticides, and interactions between them on honey bee colony performance and survival, a 2-year longitudinal study was performed in corn and soybean growing areas of Iowa. Varroa infestation and pesticide content in stored pollen were measured from 3 apiaries across a gradient of corn and soybean production areas and compared to measurements of colony health and survival. Colonies were not treated for Varroa the first year, but were treated the second year, leading to reduced Varroa infestation that was associated with larger honey bee populations, increased honey production, and higher colony survival. Pesticide detections were highest in areas with high-intensity corn and soybean production treated with conventional methods. Pesticide detections were positively associated with honey bee population size in May 2015 in the intermediate conventional (IC) and intermediate organic (IO) apiaries. Varroa populations across all apiaries in October 2015 were negatively correlated with miticide and chlorpyrifos detections. Miticide detections across all apiaries and neonicotinoid detections in the IC apiary in May 2015 were higher in colonies that survived. In July 2015, colony survival was positively associated with total pesticide detections in all apiaries and chlorpyrifos exposure in the IC and high conventional (HC) apiaries. This research suggests that Varroa are a major cause of reduced colony performance and increased colony losses, and honey bees are resilient upon low to moderate pesticide detections.

Myths and Methodologies: Standardisation in Human Physiology Research-Should We Control the Controllables?

The premise of research in human physiology is to explore a multifaceted system whilst identifying one or a few outcomes of interest. Therefore, the control of potentially confounding variables requires careful thought regarding the extent of control and complexity of standardisation. One common factor to control prior to testing is diet, as food and fluid provision may deviate from participants' habitual diets, yet a self-report and replication method can be flawed by under-reporting. Researchers may also need to consider standardisation of physical activity, whether it be through familiarisation trials, wash-out periods, or guidance on levels of physical activity to be achieved before trials. In terms of pharmacological agents, the ethical implications of standardisation require researchers to carefully consider how medications, caffeine consumption and oral contraceptive prescriptions may affect the study. For research in females, it should be considered whether standardisation between- or within-participants in regards to menstrual cycle phase is most relevant. The timing of measurements relative to various other daily events is relevant to all physiological research and so it can be important to standardise when measurements are made. This review summarises the areas of standardisation which we hope will be considered useful to anyone involved in human physiology research, including when and how one can apply standardisation to various contexts.

Myths and Methodologies: Standardisation in human physiology research-should we control the controllables?

The premise of research in human physiology is to explore a multifaceted system whilst identifying one or a few outcomes of interest. Therefore, the control of potentially confounding variables requires careful thought regarding the extent of control and complexity of standardisation. One common factor to control prior to testing is diet, as food and fluid provision may deviate from participants' habitual diets, yet a self-report and replication method can be flawed by under-reporting. Researchers may also need to consider standardisation of physical activity, whether it be through familiarisation trials, wash-out periods, or guidance on levels of physical activity to be achieved before trials. In terms of pharmacological agents, the ethical implications of standardisation require researchers to carefully consider how medications, caffeine consumption and oral contraceptive prescriptions may affect the study. For research in females, it should be considered whether standardisation between- or within-participants in regards to menstrual cycle phase is most relevant. The timing of measurements relative to various other daily events is relevant to all physiological research and so it can be important to standardise when measurements are made. This review summarises the areas of standardisation which we hope will be considered useful to anyone involved in human physiology research, including when and how one can apply standardisation to various contexts.