Search

Angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers have different pharmacologic mechanisms for blocking the effect of the renin-angiotensin-aldosterone system on the cardiovascular system. Pharmacologically, the combination of these drug classes completely blocks the deleterious effect of angiotensin in patients with heart failure. However, clinical trials have not shown a marked benefit from using this combination compared with using angiotensin-converting enzyme inhibitors alone. Patients who take combination therapy do not live longer, although they are less likely to be hospitalized for worsening symptoms. Most patients who take combination therapy will not experience marked improvement in symptoms or quality of life. [ABSTRACT FROM AUTHOR]

This paper describes an effort to bridge research and practice in residential care through implementing a program model titled Children and Residential Experiences (CARE). The strategy involves consulting at all levels of the organization to guide personnel to incorporate CARE evidence-based principles into daily practice, and fostering an organizational culture and climate that sustains the integration of CARE principles. CARE aims to promote residential care programs that serve the best interests of children. [ABSTRACT FROM AUTHOR]

Apolipoprotein E (ApoE) polymorphisms modify the risk of Alzheimer's disease with ApoE4 strongly increasing and ApoE2 modestly decreasing risk relative to the control ApoE3. To investigate how ApoE isoforms alter risk, we measured changes in proteome homeostasis in transgenic mice expressing a human ApoE gene (isoform 2, 3, or 4). The regulation of each protein's homeostasis is observed by measuring turnover rate and abundance for that protein. We identified 4849 proteins and tested for ApoE isoform-dependent changes in the homeostatic regulation of ~2700 ontologies. In the brain, we found that ApoE4 and ApoE2 both lead to modified regulation of mitochondrial membrane proteins relative to the wild-type control ApoE3. In ApoE4 mice, lack of cohesion between mitochondrial membrane and matrix proteins suggests that dysregulation of proteasome and autophagy is reducing protein quality. In ApoE2, proteins of the mitochondrial matrix and the membrane, including oxidative phosphorylation complexes, had a similar increase in degradation which suggests coordinated replacement of the entire organelle. In the liver we did not observe these changes suggesting that the ApoE-effect on proteostasis is amplified in the brain relative to other tissues. Our findings underscore the utility of combining protein abundance and turnover rates to decipher proteome regulatory mechanisms and their potential role in biology., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2024 Zuniga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Understanding how populations diverge is one of the oldest and most compelling questions in evolutionary biology. An in depth understanding of how this process operates in planktonic marine animals, where barriers for gene flow are seemingly absent, is critical to understanding the past, present, and future of ocean life. Mnemiopsis plays an important ecological role in its native habitat along the Atlantic coast of the Americas and is highly destructive in its non-native habitats in European waters. Although historical literature described three species of Mnemiopsis , the lack of stable morphological characters has led to the collapse of this group into a single species, Mnemiopsis leidyi . We generate high-quality reference genomes and use a whole-genome sequencing approach to reveal that there are two species of Mnemiopsis along its native range and show that historical divergence between the two species coincides with historical glacial melting. We define a hybridization zone between species and highlight that environmental sensing genes likely contribute to the invasive success of Mnemiopsis . Overall, this study provides insights into the fundamental question of how holopelagic species arise without clear barriers to gene flow and sheds light on the genomic mechanisms important for invasion success in a highly invasive species.

Objectives: Telemental health via videoconferencing (TMH-V) can overcome many of the barriers to accessing quality mental health care. Toward this end, in 2011, the U.S. Department of Veterans Affairs (VA) established the National Bipolar Disorders TeleHealth (BDTH) Program to provide expert mental health consultation and treatment to Veterans with bipolar spectrum disorders. Methods: Initial analyses of BDTH services suggested that participants had positive changes in quality-of-care indices and clinical outcomes; however, that evaluation was based on a limited sample of both participants and VA medical centers. We were able to confirm and expand upon those early results by using nearly eight times the number of participants and more than twice as many medical centers. Results: For the 2,456 Veterans who completed the intake to our program, there were significant improvements in some of the quality metrics (e.g., lithium use) and a 54% reduction in positive suicide screens ( p < 0.05). The Veterans who completed the initial and postprogram assessments ( n = 815) reported a 16.6% reduction in manic symptoms ( p < 0.001), a 29.3% reduction in depressive symptoms ( p < 0.001), and a 21.2% reduction in mood episodes ( p < 0.001). Additionally, these Veterans demonstrated significant improvements ( p < 0.001) in mental health-related quality of life between the two assessments. Conclusions: These analyses provide further support for the general effectiveness and safety of telemental health via videoconferencing. Future research should examine the generalizability of these findings across various subgroups (e.g., minority patients, patients in rural areas), populations, and health care systems.

Background: The effects of environmental disturbances on livestock are often observed indirectly through the variability patterns of repeated performance records over time. Sheep are frequently exposed to diverse extensive environments but currently lack appropriate measures of resilience (or sensitivity) towards environmental disturbance. In this study, random regression models were used to analyse repeated records of the fibre diameter of wool taken along the wool staple (bundle of wool fibres) to investigate how the genetic and environmental variance of fibre diameter changes with different growing environments., Results: A model containing a fifth, fourth and second-order Legendre polynomial applied to the fixed, additive and permanent environmental effects, respectively, was optimal for modelling fibre diameter along the wool staple. The additive genetic and permanent environmental variance both showed variability across the staple length trajectory. The ranking of sire estimated breeding values (EBV) for fibre diameter was shown to change along the staple and the genetic correlations decreased as the distance between measurements along the staple increased. This result suggests that some genotypes were potentially more resilient towards the changes in the growing environment compared to others. In addition, the eigenfunctions of the random regression model implied the ability to change the fibre diameter trajectory to reduce its variability along the wool staple., Conclusions: These results show that genetic variation in fibre diameter measured along the wool staple exists and this could be used to provide greater insight into the ability to select for resilience in extensively raised sheep populations., (© 2024. The Author(s).)

Purpose: The complexity of patients with mental healthcare needs cared for by clinical pharmacists is not well delineated. We evaluated the complexity of patients with schizophrenia, bipolar disorder, and major depressive disorder (MDD) in Veterans Affairs (VA) cared for by mental health clinical pharmacist practitioners (MH CPPs)., Methods: Patients at 42 VA sites with schizophrenia, bipolar disorder, or MDD in 2016 through 2019 were classified by MH CPP visits into those with 2 or more visits ("ongoing MH CPP care"), those with 1 visit ("consultative MH CPP care"), and those with no visits ("no MH CPP care"). Patient complexity for each condition was defined by medication regimen and service utilization., Results: For schizophrenia, more patients in ongoing MH CPP care were complex than those with no MH CPP care, based on all measures examined: the number of primary medications (15.3% vs 8.1%), inpatient (13.7% vs 9.1%) and outpatient (42.6% vs 29.7%) utilization, and receipt of long-acting injectable antipsychotics (36.7% vs 25.8%) and clozapine (20.5% vs 9.5%). For bipolar disorder, more patients receiving ongoing or consultative MH CPP care were complex than those with no MH CPP care based on the number of primary medications (27.9% vs 30.5% vs 17.7%) and overlapping mood stabilizers (10.1% vs 11.6% vs 6.2%). For MDD, more patients receiving ongoing or consultative MH CPP care were complex based on the number of primary medications (36.8% vs 35.5% vs 29.2%) and augmentation of antidepressants (56.1% vs 54.4% vs 47.0%) than patients without MH CPP care. All comparisons were significant (P < 0.01)., Conclusion: MH CPPs provide care for complex patients with schizophrenia, bipolar disorder, and MDD in VA., (Published by Oxford University Press on behalf of the American Society of Health-System Pharmacists 2024.)

Production animals are increasingly exposed to a wide variety of disturbances that can compromise their productivity, health and well-being. As a result, there is a growing need to be able to select animals that are more resilient to environmental disturbances. Fibre diameter variation measured along a wool staple is expected to contain information about how resilient sheep are to the disturbances of their internal and external environment. This study aimed to develop potential resilience indicators from fibre diameter variation, estimate their genetic parameters and assess whether these traits are genetically correlated across three age stages. The study used 6 140 Merino sheep from the Sheep Cooperative Research Centre Information Nucleus Flocks recorded at yearling, 2 years old, and adult ages. Eight potential traits were defined based on theory, literature and exploratory analysis, which were suggested to capture the animal's ability to resist, respond and recover from potential disturbances. Genetic evaluation of the traits was conducted using pedigree-based animal models. The traits were shown to be low to moderately heritable (0.01-0.33) when examined at each of the three age stages. The potential indicators were generally well correlated with one another within age stages. Further, the genetic correlation between the same trait measured at different age stages was moderate to high between yearling and 2 years old (0.35-0.94) and between 2 years old and adults (0.18-0.70), while slightly lower between yearling and adult estimates (0.09-0.62). These results suggest that selection for resilience indicators from fibre diameter is possible; however, further studies are warranted to refine the trait definitions and validate these indicators against other measures of health, fitness and productive performance., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Biological systems occurring in ecologically heterogeneous and spatially discontinuous habitats provide an ideal opportunity to investigate the relative roles of neutral and selective factors in driving lineage diversification. The grey mangroves (Avicennia marina) of Arabia occur at the northern edge of the species' range and are subject to variable, often extreme, environmental conditions, as well as historic large fluctuations in habitat availability and connectivity resulting from Quaternary glacial cycles. Here, we analyse fully sequenced genomes sampled from 19 locations across the Red Sea, the Arabian Sea and the Persian/Arabian Gulf (PAG) to reconstruct the evolutionary history of the species in the region and to identify adaptive mechanisms of lineage diversification. Population structure and phylogenetic analyses revealed marked genetic structure correlating with geographic distance and highly supported clades among and within the seas surrounding the Arabian Peninsula. Demographic modelling showed times of divergence consistent with recent periods of geographic isolation and low marine connectivity during glaciations, suggesting the presence of (cryptic) glacial refugia in the Red Sea and the PAG. Significant migration was detected within the Red Sea and the PAG, and across the Strait of Hormuz to the Arabian Sea, suggesting gene flow upon secondary contact among populations. Genetic-environment association analyses revealed high levels of adaptive divergence and detected signs of multi-loci local adaptation driven by temperature extremes and hypersalinity. These results support a process of rapid diversification resulting from the combined effects of historical factors and ecological selection and reveal mangrove peripheral environments as relevant drivers of lineage diversity., (© 2024 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.)

Two experiments were designed to evaluate later timepoints for fixed-time artificial insemination (FTAI) of beef heifers and cows, with the hypothesis that use of a later timepoint would allow a greater proportion of animals to express estrus prior to FTAI and result in greater conception rates among estrous females inseminated with sex-sorted semen. In Experiment 1, estrus was synchronized for 1640 heifers using the 14 d CIDR-PG protocol: insertion of an intravaginal progesterone-releasing insert (CIDR; 1.38 g progesterone) on Day -33 and removal on Day -19, and administration of prostaglandin F 2α (PG; 500 μg cloprostenol sodium) on Day -3. Heifers were inseminated at one of three FTAI timepoints: 66 h, 70 h, or 74 h after PG administration. In Experiment 2, estrus was synchronized for 414 beef cows using the 7 & 7 Synch protocol: administration of PG coincident with CIDR insertion on Day -17, gonadotropin-releasing hormone (GnRH; 100 μg gonadorelin) on Day -10, and PG coincident with CIDR removal on Day -3. Cows were inseminated at one of two FTAI timepoints: 66 h or 72 h after PG administration. In both experiments, only animals that expressed estrus prior to FTAI were inseminated with sex-sorted semen. In Experiment 1, the proportion of heifers that expressed estrus prior to FTAI (66 h: 62 %; 70 h: 67 %; 74 h: 71 %) was greater when FTAI was performed at 74 h versus 66 h (P = 0.0097); however, conception rate of heifers that expressed estrus and were serviced with sex-sorted semen did not differ among treatments (P = 0.67; 66 h: 56 %; 70 h: 53 %; 74 h: 53 %). In Experiment 2, the proportion of cows expressing estrus prior to FTAI did not differ between treatments (P = 0.30; 66 h: 71 %; 72 h: 76 %). Additionally, conception rate of estrous cows inseminated with sex-sorted semen did not differ between treatments (P = 0.24; 66 h: 45 %; 72 h: 40 %). These results indicate that performing FTAI later following the 14 d CIDR-PG protocol increases the proportion of heifers that express estrus and are serviced with sex-sorted semen but does not improve conception rates. Later timing of FTAI following the 7 & 7 Synch protocol was not observed to increase the proportion of cows expressing estrus prior to FTAI or improve conception rates among estrous cows inseminated with sex-sorted semen. Together, these results provide further insight into optimal timing of FTAI when using sex-sorted semen., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A series of experiments was designed to evaluate treatment schedules for control of the estrous cycle in which luteolysis is induced prior to atresia of the first follicular wave following a long-term progestin presynchronization treatment in beef heifers. The overarching hypothesis was that the proportion of heifers undergoing luteolysis and expressing estrus following PG administration would be affected by the duration of treatment with an intravaginal progesterone-releasing insert (CIDR; 1.38 g progesterone) and/or by the interval from CIDR removal to prostaglandin F 2ɑ (PG; 500 μg cloprostenol) administration. In each experiment, heifers were blocked by reproductive tract score (RTS) and body weight (BW) and were assigned randomly within block to treatment. In Experiment 1, heifers (n = 91) were assigned to one of four treatments in a 2 x 2 factorial design: presynchronization via CIDR treatment for either 14 d or 18 d with administration of PG either 8 d or 9 d following CIDR removal. In Experiment 2, heifers (n = 63) were assigned to receive administration of PG either 9 d or 10 d following a 14 d CIDR presynchronization. In Experiment 3, heifers (n = 83) were assigned to receive administration of PG either 9 d or 16 d following a 14 d CIDR presynchronization. In Experiment 1, there was a tendency for a greater proportion of heifers to express estrus by 96 h after PG administration when PG administration occurred 9 d versus 8 d after CIDR removal (P = 0.07). Additionally, serum estradiol (E 2 ) concentrations were greater at the time of PG administration when PG was administered 9 d versus 8 d after CIDR removal following an 18 d CIDR treatment (P = 0.006). In Experiment 2, pregnancy rate to AI (P/AI) was greater among heifers receiving PG administration 9 d versus 10 d after CIDR removal (P = 0.03). There was a tendency for largest follicle diameter (LFD) to be greater among non-estrous heifers receiving PG administration 10 d versus 9 d after CIDR removal when measured at timed AI (P < 0.08). In Experiment 3, there was a tendency for serum progesterone (P 4 ) concentrations at the time of PG administration to be greater among heifers receiving PG administration 16 d versus 9 d after CIDR removal (P = 0.07). These results provide a preliminary evaluation of the feasibility of inducing luteolysis prior to atresia of the first follicular wave following long-term progestin presynchronization., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Six lineages of Mycobacterium tuberculosis sensu stricto (which excludes M. africanum) are described. Single-country or small observational data suggest differences in clinical phenotype between lineages. We present strain lineage and clinical phenotype data from 12,246 patients from 3 low-incidence and 5 high-incidence countries. We used multivariable logistic regression to explore the effect of lineage on site of disease and on cavities on chest radiography, given pulmonary TB; multivariable multinomial logistic regression to investigate types of extra-pulmonary TB, given lineage; and accelerated failure time and Cox proportional-hazards models to explore the effect of lineage on time to smear and culture-conversion. Mediation analyses quantified the direct effects of lineage on outcomes. Pulmonary disease was more likely among patients with lineage(L) 2, L3 or L4, than L1 (adjusted odds ratio (aOR) 1.79, (95% confidence interval 1.49-2.15), p<0.001; aOR = 1.40(1.09-1.79), p = 0.007; aOR = 2.04(1.65-2.53), p<0.001, respectively). Among patients with pulmonary TB, those with L1 had greater risk of cavities on chest radiography versus those with L2 (aOR = 0.69(0.57-0.83), p<0.001) and L4 strains (aOR = 0.73(0.59-0.90), p = 0.002). L1 strains were more likely to cause osteomyelitis among patients with extra-pulmonary TB, versus L2-4 (p = 0.033, p = 0.008 and p = 0.049 respectively). Patients with L1 strains showed shorter time-to-sputum smear conversion than for L2. Causal mediation analysis showed the effect of lineage in each case was largely direct. The pattern of clinical phenotypes seen with L1 strains differed from modern lineages (L2-4). This has implications for clinical management and could influence clinical trial selection strategies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Du et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: We investigated whether the Death/Suicide Implicit Association Test (D/S-IAT) predicted suicidal ideation (SI) in psychiatric inpatients., Methods: One hundred eighty veterans admitted for either SI or suicidal behavior (SB) (the primary sample) (N = 90) or alcohol detoxification (N = 90) completed the D/S-IAT and scales measuring SI. Correlation and regression coefficients were measured between the D/S-IAT (as a full-scale or dichotomized score [D > 0]) and self-reported current or imminent SI (over the next 1-3 days)., Results: In the primary sample, the full-scale D/S-IAT was significantly correlated with the intensity of current SI (r = 0.22, p = 0.04) and especially with wishes to be dead (r = 0.35, p < 0.001). The intensity of imminent SI was significantly predicted by the full-scale (p = 0.02) and dichotomized D/S-IAT score (p = 0.05) in a multiple regression model. However, no significant associations were observed when both the D/S-IAT score and current (present/absent) or imminent SI (occurred/did not occur) were dichotomous measures. In participants receiving alcohol detoxification, the D/S-IAT significantly predicted only wishes to be dead (r = 0.33, p < 0.001)., Conclusion: The full-scale D/S-IAT score predicted the current intensity of wishes to be dead in both inpatient samples, and current and imminent SI in participants admitted for SI/SB. The dichotomized D/S-IAT score did not predict the simple occurrence of SI., (© 2023 American Association of Suicidology. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Objective: Fragile X Syndrome (FXS) is the leading monogenic cause of intellectual disability and autism spectrum disorder. Currently, there are no established biomarkers for predicting and monitoring drug effects in FXS, and no approved therapies are available. Previous studies have shown electrophysiological changes in the brain using electroencephalography (EEG) in individuals with FXS and animal models. These changes may be influenced by drug therapies. In this study, we aimed to assess the reliability of resting-state EEG measures in individuals with FXS, which could potentially serve as a biomarker for drug discovery., Methods: We collected resting-state EEG data from 35 individuals with FXS participating in placebo-controlled clinical trials (23 males, 12 females; visit age mean+/-std 25.6 +/-8.3). The data were analyzed for various spectral features using intraclass correlation analysis to evaluate test-retest reliability. The intervals between EEG recordings ranged from same-day measurements to up to six weeks apart., Results: Our results showed high reliability for most spectral features, with same-day reliability exceeding 0.8. Features of interest demonstrated ICC values of 0.60 or above at longer intervals. Among the features, alpha band relative power exhibited the highest reliability., Conclusion: These findings indicate that resting-state EEG can provide consistent and reproducible measures of brain activity in individuals with FXS. This supports the potential use of EEG as an objective biomarker for evaluating the effects of new drugs in FXS., Significance: The reliable measurements obtained from power spectrum-based resting-state EEG make it a promising tool for assessing the impact of small molecule drugs in FXS., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rui Liu, Ernest V. Pedapati, Lauren M. Schmitt, Rebecca C. Shaffer, Elizabeth G. Smith, Kelli C. Dominick, Lisa A. DeStefano, Grace Westerkamp, Paul Horn, and John A. Sweeney have no conflict with this work. Craig A. Erickson is a current consultant to Impel, Scioto Bioscience, and Forge.

Background: Rape scholarship in West Africa is growing, but studies often utilize Westernized approaches. A 2018 study using a randomized survey design assessing rape among Liberian girls incorporated modified survey design methods to improve ethical data collection relevant to the cultural and contextual contexts. This article presents the findings of a thorough review of rape scholarship and design methods., Methods: Based on a qualitative analysis of field notes by the research team, we present lessons learned and best practices identified in the planning, pilot-testing, and implementation phases of the 2018 Liberian study., Results: This study helps inform innovative design methods striving to (1) avoid using obtrusively graphic language or labels prevalent in westernized studies, (2) authentically collaborate with African experts to adapt strategies to be culturally appropriate and contextually relevant, and (3) create respectfully transparent interactions with respondents and communities. Extensive research preparation and inclusive regional expertise inform compassionate methodological techniques, yielding improved Afro-centric participant experience, low participant attrition, and quality data use in policymaking. (4) Conclusions: This article offers innovative design methods to study rape, placing context, culture, and participants at the heart. Authentic collaboration with national-level experts is vital for conducting more reliable and ethical field research in the African region.

Background: We performed a preimplementation assessment of workflows, resources, needs, and antibiotic prescribing practices of trainees and practicing dentists to inform the development of an antibiotic-stewardship clinical decision-support tool (CDST) for dentists., Methods: We used a technology implementation framework to conduct the preimplementation assessment via surveys and focus groups of students, residents, and faculty members. Using Likert scales, the survey assessed baseline knowledge and confidence in dental providers' antibiotic prescribing. The focus groups gathered information on existing workflows, resources, and needs for end users for our CDST., Results: Of 355 dental providers recruited to take the survey, 213 (60%) responded: 151 students, 27 residents, and 35 faculty. The average confidence in antibiotic prescribing decisions was 3.2 ± 1.0 on a scale of 1 to 5 (ie, moderate). Dental students were less confident about prescribing antibiotics than residents and faculty ( P < .01). However, antibiotic prescribing knowledge was no different between dental students, residents, and faculty. The mean likelihood of prescribing an antibiotic when it was not needed was 2.7 ± 0.6 on a scale of 1 to 5 (unlikely to maybe) and was not meaningfully different across subgroups ( P = .10). We had 10 participants across 3 focus groups: 7 students, 2 residents, and 1 faculty member. Four major themes emerged, which indicated that dentists: (1) make antibiotic prescribing decisions based on anecdotal experiences; (2) defer to physicians' recommendations; (3) have limited access to evidence-based resources; and (4) want CDST for antibiotic prescribing., Conclusions: Dentists' confidence in antibiotic prescribing increased by training level, but knowledge did not. Trainees and practicing dentists would benefit from a CDST to improve appropriateness of antibiotic prescribing.

Abstract: This tutorial describes a system for rapidly yet rigorously assessing the quality of randomized controlled trials (RCTs). The system has 7 criteria, represented by the acronym "BIS FOES." The BIS FOES system directs readers to assess RCTs based on the following 7 criteria: the RCT's use (or not) of effective (1) Blinding; the RCT's use (or not) of (2) Intent-to-Treat Analysis; the RCT's (3) Size and other information reflecting the effectiveness of randomization; the amount of sample lost during (4) Follow-up; the (5) Outcomes examined by the RCT (specifically, the outcome measures used by the RCT), the (6) Effects reported (ie, the statistical and clinical significance of the RCT's primary, secondary, and safety findings), and any (7) Special Considerations (ie, additional strengths, limitations, or notable features of the RCT). The first 6 criteria are of basic importance to the assessment of every RCT, whereas the Special Considerations criteria allows the system to be expanded to include virtually any other important aspect of the RCT. This tutorial explains the importance of these criteria and how to assess them. This tutorial also describes how many BIS FOES criteria can be initially assessed from the RCT Abstract while also directing readers to specific locations in the RCT article where additional important information can be found. We hope that the BIS FOES system will help healthcare trainees, but also potentially clinicians, researchers, and the general public, rapidly and thoroughly assess RCTs., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To describe the methods for the in-person musculoskeletal (MSK) assessment of the RISE FOR HEALTH (RISE) study, a population-based multicenter prospective cohort study designed to identify factors associated with bladder health (BH) conducted by the Prevention of Lower Urinary Tract Symptoms Research Consortium (PLUS)., Methods: A subset of RISE participants who express interest in the in-person assessment are screened to ensure eligibility (planned n = 525). Eligible consenting participants are asked to complete a standardized MSK assessment to evaluate core stability (four component core stability test, lumbar spine pain (seated slump test), pelvic girdle pain, (sacroiliac joint, anterior superior iliac spine, pubic symphysis tenderness, and pelvic girdle pain provocation test), hip pain (flexion, abduction, internal rotation and flexion, adduction and external rotation) and pelvic girdle function (active straight leg raise). Participants are also asked to complete the Short Physical Performance Battery to measure balance, gait speed, lower extremity strength, and functional capacity., Results: Detailed online and in-person MSK training sessions led by physical therapy were used to certify research staff at each clinical center before the start of RISE in-person assessments. All evaluators exceeded the pre-specified pass rates., Conclusions: The RISE in-person MSK assessment will provide further insight into the role of general body MSK health and dysfunction and the spectrum of BH., (© 2022 Wiley Periodicals LLC.)

Within microeukaryotes, genetic variation and functional variation sometimes accumulate more quickly than morphological differences. To understand the evolutionary history and ecology of such lineages, it is key to examine diversity at multiple levels of organization. In the dinoflagellate family Symbiodiniaceae, which can form endosymbioses with cnidarians ( e.g ., corals, octocorals, sea anemones, jellyfish), other marine invertebrates ( e.g. , sponges, molluscs, flatworms), and protists ( e.g ., foraminifera), molecular data have been used extensively over the past three decades to describe phenotypes and to make evolutionary and ecological inferences. Despite advances in Symbiodiniaceae genomics, a lack of consensus among researchers with respect to interpreting genetic data has slowed progress in the field and acted as a barrier to reconciling observations. Here, we identify key challenges regarding the assessment and interpretation of Symbiodiniaceae genetic diversity across three levels: species, populations, and communities. We summarize areas of agreement and highlight techniques and approaches that are broadly accepted. In areas where debate remains, we identify unresolved issues and discuss technologies and approaches that can help to fill knowledge gaps related to genetic and phenotypic diversity. We also discuss ways to stimulate progress, in particular by fostering a more inclusive and collaborative research community. We hope that this perspective will inspire and accelerate coral reef science by serving as a resource to those designing experiments, publishing research, and applying for funding related to Symbiodiniaceae and their symbiotic partnerships., Competing Interests: Anastazia T. Banaszak and James Davis Reimer are Academic Editors for PeerJ., (© 2023 Davies et al.)

Objective: To summarize the current state of the literature regarding emotion dysregulation (ED) in syndromic intellectual disabilities (S-IDs) in 6 of the most common forms of S-IDs-Down syndrome, fragile X syndrome (FXS), tuberous sclerosis complex, Williams syndrome, Prader-Willi syndrome, and Angelman syndrome-and to determine future research directions for identification and treatment of ED., Method: PubMed bibliographic database was searched from date of inception to May 2021. PRISMA 2020 guidelines were followed with the flowchart, table of included studies, list of excluded studies, and checklist provided. Filters applied included human research and English. Only original research articles were included in the final set, but review articles were used to identify secondary citations of primary studies. All articles were reviewed for appropriateness by 2 authors and summarized. Inclusion criteria were met by 145 articles (Down syndrome = 29, FXS = 55, tuberous sclerosis complex = 11, Williams syndrome = 18, Prader-Willi syndrome = 24, Angelman syndrome = 8)., Results: Each syndrome review was summarized separately and further subdivided into articles related to underlying neurobiology, behaviors associated with ED, assessment, and targeted intervention. FXS had the most thorough research base, followed by Down syndrome and Prader-Willi syndrome, with the other syndromes having more limited available research. Very limited research was available regarding intervention for all disorders except FXS., Conclusion: Core underlying characteristics of S-IDs appear to place youth at higher risk for ED, but further research is needed to better assess and treat ED in S-IDs. Future studies should have a standard assessment measure of ED, such as the Emotion Dysregulation Inventory, and explore adapting established curricula for ED from the neurotypical and autism spectrum disorder fields., (Copyright © 2022 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by core impairments in social communication as well as restricted, repetitive patterns of behavior and/or interests. Individuals with ASD, which includes about 2% of the US population, have challenges with activities of daily living and suffer from comorbid medical and mental health concerns. There are no drugs indicated for the core impairments of ASD. As such, there is a significant need for the development of new medication strategies for individuals with ASD. This first-in-human placebo-controlled, double-blind, crossover study investigated the safety (primary objective) and efficacy of oral SB-121, a combination of L. reuteri, Sephadex® (dextran microparticles), and maltose administered once daily for 28 days in 15 autistic participants. SB-121 was safe and well tolerated. SB-121-associated directional improvements in adaptive behavior measured by Vineland-3 and social preference as measured with eye tracking were noted. These results provide support for further clinical evaluation of SB-121 as a treatment in autistic patients. To evaluate the safety and tolerability of multiple doses of SB-121 in subjects with autism spectrum disorder. Single-center, randomized, placebo-controlled, double-blind, crossover trial. 15 patients with autism spectrum disorder were randomized and analyzed. Daily dosing of SB-121 or placebo for 28 days, followed by approximately a 14 day washout, then 28 days of dosing with other treatment. Incidence and severity of adverse events, presence of Limosilactobacillus reuteri and Sephadex® in stool, and incidence of bacteremia with positive L. reuteri identification. Additional outcomes include changes from baseline on cognitive and behavior tests as well as biomarker levels. Adverse event rates were similar between SB-121 and placebo, with most reported as mild. There were no severe or serious adverse events. No participants had features of suspected bacteremia or notable changes in vital signs, safety laboratory, or ECG parameters from baseline. There was a statistically significant increase from baseline in the Vineland-3 Adaptive Behavior Composite score (p = 0.03) during SB-121 treatment. There was a trend for increased social/geometric viewing ratio following SB-121 treatment compared to placebo. SB-121 was safe and well tolerated. SB-121-associated directional improvements in adaptive behavior measured by Vineland-3 and social preference as measured with eye tracking were noted.Trial registration: clinicaltrials.gov Identifier: NCT04944901., (© 2023. The Author(s).)

Venom is a complex trait with substantial inter- and intraspecific variability resulting from strong selective pressures acting on the expression of many toxic proteins. However, understanding the processes underlying toxin expression dynamics that determine the venom phenotype remains unresolved. By interspecific comparisons we reveal that toxin expression in sea anemones evolves rapidly and that in each species different toxin family dictates the venom phenotype by massive gene duplication events. In-depth analysis of the sea anemone, Nematostella vectensis, revealed striking variation of the dominant toxin (Nv1) diploid copy number across populations (1-24 copies) resulting from independent expansion/contraction events, which generate distinct haplotypes. Nv1 copy number correlates with expression at both the transcript and protein levels with one population having a near-complete loss of Nv1 production. Finally, we establish the dominant toxin hypothesis which incorporates observations in other venomous lineages that animals have convergently evolved a similar strategy in shaping their venom., (© 2023. The Author(s).)

Traumatic brain injuries (TBI) and posttraumatic stress disorder (PTSD) are commonly observed comorbid occurrences among military service members and veterans (SMVs). In this cross-sectional study, SMVs with a history of TBI were stratified into symptomatic and asymptomatic PTSD groups based on posttraumatic stress checklist-civilian (PCL-C) total scores. Blood-based biomarkers were assessed, and significant differential markers were associated with scores from multiple neurobehavioral self-report assessments. PCL-C cutoffs were total scores >50 (PTSD symptomatic) and <25 (asymptomatic). Cytokines IL6, IL8, TNFα, and IL10 were significantly elevated (p < 0.05−0.001) in the TBI+/PTSD symptomatic group compared to the TBI+/asymptomatic group. Cytokine levels of IL8, TNFα, and IL10 were strongly associated with PCL-C scores (0.356 < r > 0.624 for all, p < 0.01 for all), while TNFα and IL10 were additionally associated with NSI totals (r = 0.285 and r = 0.270, p < 0.05, respectively). This is the first study focused on PTSD symptom severity to report levels of circulating pro-inflammatory IL8, specifically in SMVs with TBI. These data suggest that within the military TBI population, there are unique cytokine profiles that relate to neurobehavioral outcomes associated with TBI and PTSD.

Moderate/severe traumatic brain injury (TBI) causes injury patterns with heterogeneous pathology producing varying outcomes for recovery. Extracellular vesicles (EVs) are particles containing a myriad of molecules involved in cell signaling. EVs may hold promise as biomarkers in TBI because of their encapsulation, including improved stability/decreased degradation. A subset of subjects with and without TBI from a prospective, observational trial of critically ill trauma patients were analyzed. Total EV levels of glial (glial fibrillary acidic protein; GFAP) and neuronal/axonal (ubiquitin carboxy-terminal hydrolase L1 [UCH-L1], neurofilament light chain [NfL], and total-tau) proteins were measured using single-molecule array technology. Protein levels were winsorized to address outliers and log transformed for analysis. Patients with multiple injuries ( n  = 41) and isolated body injury ( n  = 73) were of similar age and sex. Patients with multiple injuries were, as expected, more severely injured with higher Injury Severity Scores (29 [26-41] vs. 21 [14-26], p  < 0.001) and lower Glasgow Coma Scale scores (12 [4-13] vs. 13 [13-13], p  < 0.001). Total body EVs of GFAP, UCH-L1, and NfL were higher in those with multiple injuries (1768 [932-4780] vs. 239 [63-589], p  < 0.001; 75.4 [47.8-158.3] vs. 41.5 [21.5-67.1], p  = 0.03; 7.5 [3.3-12.3] vs. 2.9 [2.1-4.8], p  < 0.001, respectively). There was a moderate correlation between the Head Abbreviated Injury Score and GFAP (free circulating rho = 0.62, EV rho = 0.64; both p  < 0.001). Brain-derived proteins contained in EV holds promise as an informative approach to biomarker measurement after TBI in hospitalized patients. Future evaluation and longitudinal studies are necessary to draw conclusions regarding the clinical utility of these biomarkers., Competing Interests: No competing financial interests exist., (© Vivian A. Guedes et al., 2022; Published by Mary Ann Liebert, Inc.)

The incidence and implications of disparate ovarian and uterine development during the peripubertal period were evaluated in two experiments. In Experiment 1, two consecutive pre-breeding evaluations were performed on 469 heifers. In Experiment 2, data from 22,174 heifers were retrospectively analyzed. For heifers in both experiments, ovarian and uterine maturity were independently assessed via transrectal evaluation, and a two-digit reproductive tract score (RTS: first digit = ovarian; second digit = uterine) was assigned. Measures of the physical maturity of heifers were recorded at the time of pre-breeding evaluation. Heifers were subjected to 14-day progestin-based protocols for synchronization of estrus, and artificial insemination (AI) was performed. Pregnancy diagnosis was performed via transrectal ultrasonography. Incidence of disparate ovarian and uterine score was 33.7 % (158/469) in Experiment 1 % and 16.3 % (3622/22,174) in Experiment 2. Observations of disparate ovarian and uterine maturity were correlated with physical maturity. Heifers with RTS < 3-3 demonstrated poor reproductive performance, as lesser proportions of these animals conceived to the first AI service in Experiment 2 (P < 0.01) or throughout the breeding season in Experiment 1 (P = 0.03). Conception did not differ between heifers assigned congruent or disparate scores of greater than RTS = 3-3. Disparities in ovarian and uterine development are likely observed as the result of rapid, yet asynchronous growth of reproductive tissues during the peripubertal period and are not indicative of inherently reduced potential for fertility. Independent assessment of ovarian and uterine maturity may increase precision in characterizing physiologic maturity of mixed groups of prepubertal, peripubertal, and pubertal heifers., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Echinometra is the most widespread genus of sea urchin and has been the focus of a wide range of studies in ecology, speciation, and reproduction. However, available genetic data for this genus are generally limited to a few select loci. Here, we present a chromosome-level genome assembly based on 10x Genomics, PacBio, and Hi-C sequencing for Echinometra sp. EZ from the Persian/Arabian Gulf. The genome is assembled into 210 scaffolds totaling 817.8 Mb with an N50 of 39.5 Mb. From this assembly, we determined that the E. sp. EZ genome consists of 2n = 42 chromosomes. BUSCO analysis showed that 95.3% of BUSCO genes were complete. Ab initio and transcript-informed gene modeling and annotation identified 29,405 genes, including a conserved Hox cluster. E. sp. EZ can be found in high-temperature and high-salinity environments, and we therefore compared E. sp. EZ gene families and transcription factors associated with environmental stress response ("defensome") with other echinoid species with similar high-quality genomic resources. While the number of defensome genes was broadly similar for all species, we identified strong signatures of positive selection in E. sp. EZ noncoding elements near genes involved in environmental response pathways as well as losses of transcription factors important for environmental response. These data provide key insights into the biology of E. sp. EZ as well as the diversification of Echinometra more widely and will serve as a useful tool for the community to explore questions in this taxonomic group and beyond., (© The Author(s) 2022. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Formalin-fixed, paraffin-embedded (FFPE) tissues are banked in large repositories to cost-effectively preserve valuable specimens for later study. With the rapid growth of spatial proteomics, FFPE tissues can serve as a more accessible alternative to more commonly used frozen tissues. However, extracting proteins from FFPE tissues is challenging due to cross-links formed between proteins and formaldehyde. Here, we have adapted the nanoPOTS sample processing workflow, which was previously applied to single cells and fresh-frozen tissues, to profile protein expression from FFPE tissues. Following the optimization of extraction solvents, times, and temperatures, we identified an average of 1312 and 3184 high-confidence master proteins from 10 μm thick FFPE-preserved mouse liver tissue squares having lateral dimensions of 50 and 200 μm, respectively. The observed proteome coverage for FFPE tissues was on average 88% of that achieved for similar fresh-frozen tissues. We also characterized the performance of our fully automated sample preparation and analysis workflow, termed autoPOTS, for FFPE spatial proteomics. This modified nanodroplet processing in one pot for trace samples (nanoPOTS) and fully automated processing in one pot for trace sample (autoPOTS) workflows provides the greatest coverage reported to date for high-resolution spatial proteomics applied to FFPE tissues. Data are available via ProteomeXchange with identifier PXD029729.