LAI-ART Awareness, Willingness, Barriers and Facilitators among Black Sexual Minority Men Living with HIV in the US South.

Black sexual minority men (BSMM) continue to bear a disproportionate burden of HIV in the United States, with the highest incidence and prevalence in the southern region of the country. In Texas, BSMM living with HIV (BSMM+) have the lowest rates of viral suppression of all SMM and have lower antiretroviral treatment (ART) adherence than white and Hispanic SMM. Long-acting injectable ART (LAI-ART) can potentially overcome several barriers to daily oral ART adherence (e.g., stigma, forgetfulness, pill fatigue). However, little is known about the knowledge, willingness, barriers, and facilitators regarding LAI-ART among BSMM+. From July 2022 to September 2023, we conducted in-depth, semi-structured interviews with 27 BSMM+ from the Houston and Dallas Metropolitan Areas, Texas. Data were analyzed using a thematic analysis approach. Most men knew about LAI-ART, but their understanding varied based on their existing sources of information. Some men were enthusiastic, some were cautious, and some reported no interest in LAI-ART. Barriers to LAI-ART included a lack of public insurance coverage of LAI-ART; fear of needles and side effects; the frequency of injection visits; the requirement of viral suppression before switching from oral ART to LAI-ART; and satisfaction with oral daily ART. Motivators of LAI-ART uptake included the eliminated burden of daily pills and reduced anxiety about possibly missing doses. BSMM+ may be among those who could most benefit from LAI-ART, though more research is needed to understand which factors influence their willingness and how the barriers to LAI-ART might be addressed, particularly among diverse communities of SMM of color.

How Intimate Partner Violence Is Influenced by Social Identity Among Sexual Minority Men.

Purpose: Sexual minority men (SMM) experience intimate partner violence (IPV) at disproportionately high rates. The objective of this article was to identify the experiences of SMM and health care providers on how social identity impacts IPV. Methods: SMM participants (N = 23) were recruited from online community settings and a lesbian, gay, bisexual, transgender, queer, and others (LGBTQ+) organization in Los Angeles; providers (N = 10) were recruited from LGBTQ+ organizations. Semistructured interviews were audio recorded and transcribed verbatim. An applied thematic analysis approach was implemented to create memos, inductively generate a codebook, apply codes to the transcripts, and identify key themes in data. Results: Three main themes were identified. The first theme was weaponizing social identity to control a partner, which had three subthemes: (1) immigration status, race/ethnicity, and skin color, (2) threatening to "out" the partner's sexual orientation, and (3) abusing power inequity. Men who perpetrated IPV often used minority identities or undisclosed sexuality to leverage power over their partner. The second theme was use of IPV to establish masculinity, by exerting power over the more "feminine" partner. The third theme was internalized homophobia as a root cause of IPV, which details how internalized homophobia was often expressed in violent outbursts toward partners. Conclusion: These findings highlight how IPV among SMM can be influenced by social and sexual identity. Future research must consider socially constructed power structures and the multiple identities of SMM when developing interventions to address IPV in this population.

Bystander Intervention in Coercive Control: Do Ethnic Identity and Acceptance of Coercive Control Influence Willingness to Intervene?

Previous intimate partner violence research and social psychological theory have highlighted that ethnicity and level of harm are both factors that have the potential to influence bystander willingness to intervene in, as well as the acceptance of intimate partner violence between couples. Little research has been conducted on the general willingness of bystanders to intervene in, or the level of acceptance of coercive control. This is the first study to explore whether the likelihood of bystander willingness to intervene is influenced by participant gender, the ethnicity of the couple involved in a hypothetical scenario of coercive control, and by differing levels of abusive behavior. In this study, we also explored the influence of participants' acceptance of coercive control. A semi-experimental design was used, utilizing an online community sample sourced through social media of 346 adult participants across Australia. The participants were randomly allocated to read a fictional coercive control scenario detailing either low or high harm instances of coercive control. Within the online survey the ethnicity of the couple was manipulated with participants' randomly allocated to read a scenario about a couple with the same ethnicity as them (Australian of British or European descent) or a couple with Indian Australian ethnicity. The results showed the participants were significantly more willing to intervene in the coercive control scenario when the couple shared the same ethnicity as them. In response to the low harm scenarios, participants were significantly more accepting of coercive control if the couple were Indian Australian. However, males responding to high harm scenarios were more accepting of coercive control if the couple shared the same ethnic identity as them. The implications from these findings for theory and future bystander intervention programs are discussed.

Nutritional programming in Nile tilapia (Oreochromis niloticus): Effect of low dietary protein on growth and the intestinal microbiome and transcriptome.

Nutritional programming is the idea that early nutrient contributions can influence organismal structure or function and is documented in a variety of vertebrates, yet studies in fish are largely lacking. Tilapia are an important foodfish, with global production having increased rapidly since the 1990s. They exhibit high disease-resistance and grow well on formulated feeds which makes them an ideal aquaculture species, however incorporating high quality proteins into feeds can be costly. As feed constitutes 50-70% of total production costs in aquaculture, reducing protein content could curb these costs and increase revenue. Thus, we examined the effects of feeding Nile tilapia (O. niloticus) fry a restricted protein diet for the first 7-21 days on growth, gut microbial flora, and the intestinal transcriptome. Fish were fed either a 25% restricted or 48% control crude protein starter (ST) diet for up to 21 days and then switched to a 25% or 38% control crude protein growout (GO) diet. Fish fed a 25% ST diet for 14 days followed by a 38% GO diet had significantly higher lengths and weights and better feed efficiency than fish fed the control 48% ST and 38% GO diet after 56 days of culture. Growth of fry on the 25% ST, 7-day/38% GO and the 25% ST,7-day/25% GO diets did not differ from the those fed the control protein diets, while fish fed the 25% ST diet for 21 days had significantly lower growth and survival rates. We observed no significant differences in either alpha or beta diversity of the gut microbial flora between diets, however species richness (Shannon Index) was higher in fry fed the 25% protein ST diet regardless of the GO diet. Similarly, fish fed the 25% ST diet for 14 days followed by the 38% GO diet had minimal changes to the intestinal transcriptome relative to fish fed the control 48% ST and 38% GO diet. However, those fed 25% ST and GO diets for the entire 56 days exhibited substantial differences in the gut transcriptome from other groups showing gene expression profiles characteristic of detrimental changes to gut physiology, protein metabolism and immune function. Results suggest protein restriction for up to 14 days early in development leads to enhanced growth and feed efficiency with minimal effects on gut microbes or intestinal function. Protein restriction beyond this period appears detrimental to fish growth and health as underscored by expression of disease related genes and higher mortality rates.

Intimate Partner Violence and the Sexual Health of Sexual Minority Men.

Purpose: This qualitative study explores the pathways by which various forms of intimate partner violence (IPV) impact the sexual health behaviors of cisgender identified sexual minority men (SMM). Methods: Semi-structured interviews were conducted with 23 racially and ethnically diverse SMM who recently experienced IPV and 10 clinical and social service providers focused on how experiences of IPV directly or indirectly influences sexual risk as well as engagement in HIV prevention behaviors (e.g., pre-exposure prophylaxis [PrEP] use). Applied thematic analysis, including cycles of analytic memo writing and coding, aided the identification of patterns across the data. Results: Analyses yielded three overarching themes: use of condoms, use of PrEP, and HIV and sexually transmitted infections (STIs). Participants described different ways condom use or nonuse was a mechanism by which power and/or control might be asserted by one partner over the other partner. A range of responses to questions about PrEP were identified, including partners encouraging PrEP use, as well as avoidance of conversations about PrEP or actual PrEP use, to prevent experiencing aggression or IPV from partners. Responses regarding HIV/STIs included those ranging from a new diagnosis being a potential trigger for violence to the exploitation of status to control partners. Conclusion: These findings suggest that in relationships with IPV, HIV prevention strategies can be sources of relationship control and trigger abuse. Addressing IPV may help to prevent HIV/STI transmission and promote the health of SMM. In addition, long-acting formulations of PrEP may be a promising strategy for SMM experiencing IPV when oral PrEP medications may be a risk factor for violence.

The use of autologous skeletal muscle progenitor cells for adjunctive treatment of presumptive urethral sphincter mechanism incompetence in female dogs.

BACKGROUND: Urethral sphincter mechanism incompetence (USMI) is a common problem in female dogs, but some dogs fail to achieve continence with standard treatment. Urethral submucosal injection of autologous skeletal muscle progenitor cells (skMPCs) previously has been shown to restore urethral function in a canine model of USMI. HYPOTHESIS/OBJECTIVE: To determine if urethral submucosal injection of skMPC alters continence in dogs with USMI that had previously failed standard medical management. We hypothesized that the injections would lead to improved continence. ANIMALS: Fifteen client-owned dogs with USMI that had failed standard medical management. METHODS: Dogs were prospectively enrolled into a single-armed clinical trial. Once enrolled, a triceps muscle of each dog was biopsied; the tissue specimens were digested, cultured, and expanded to 100 million cells before injection into the urethral submucosa using a surgical approach. Continence was assessed at baseline and 3, 6, 12, and 24 months post-injection using continence scores and urethral pressure profilometry. RESULTS: Median continence scores increased significantly from baseline at 3, 6, 12, and 24 months. Increases were seen in 14 of 15 dogs with 7, 6 or 1 dog achieving scores of 5, 4 or 3, respectively. Additional medication was required to achieve continence in all but 2 dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Urethral submucosal injection of skMPC can be used adjunctively to improve continence in dogs with difficult to manage USMI. The procedure is labor intensive but well tolerated; most dogs will require continued medication to remain continent.

Achieving High Dialysis Dose via Continuous Renal Replacement Therapy in the Setting of Metformin Associated Lactic Acidosis. A Case Series.

Severe and life-threatening cases of metformin-associated lactic acidosis (MALA) are treated with renal replacement therapy. Intermittent hemodialysis is recommended, as it achieves rapid more elimination of metformin compared to continuous renal replacement therapy (CRRT). This case series describes 4 patients, 2 with acute metformin intoxications and 2 with insidious metformin toxicity. All were treated using a novel approach with dual CRRT to achieve rapid elimination of metformin. Three of the 4 patients survived to hospital discharge. Dual CRRT may be an effective alternative when dialysis is not readily available.

Effects of the soil microbiome on the demography of two annual prairie plants.

Both mutualistic and pathogenic soil microbes are known to play important roles in shaping the fitness of plants, likely affecting plants at different life cycle stages.In order to investigate the differential effects of native soil mutualists and pathogens on plant fitness, we compared survival and reproduction of two annual tallgrass prairie plant species (Chamaecrista fasciculata and Coreopsis tinctoria) in a field study using 3 soil inocula treatments containing different compositions of microbes. The soil inocula types included fresh native whole soil taken from a remnant prairie containing both native mutualists and pathogens, soil enhanced with arbuscular mycorrhizal (AM) fungi derived from remnant prairies, and uninoculated controls.For both species, plants inoculated with native prairie AM fungi performed much better than those in uninoculated soil for all parts of the life cycle. Plants in the native whole prairie soil were either generally similar to plants in the uninoculated soil or had slightly higher survival or reproduction.Overall, these results suggest that native prairie AM fungi can have important positive effects on the fitness of early successional plants. As inclusion of prairie AM fungi and pathogens decreased plant fitness relative to prairie AM fungi alone, we expect that native pathogens also can have large effects on fitness of these annuals. Our findings support the use of AM fungi to enhance plant establishment in prairie restorations.

Mutations in NCAPG2 Cause a Severe Neurodevelopmental Syndrome that Expands the Phenotypic Spectrum of Condensinopathies.

The use of whole-exome and whole-genome sequencing has been a catalyst for a genotype-first approach to diagnostics. Under this paradigm, we have implemented systematic sequencing of neonates and young children with a suspected genetic disorder. Here, we report on two families with recessive mutations in NCAPG2 and overlapping clinical phenotypes that include severe neurodevelopmental defects, failure to thrive, ocular abnormalities, and defects in urogenital and limb morphogenesis. NCAPG2 encodes a member of the condensin II complex, necessary for the condensation of chromosomes prior to cell division. Consistent with a causal role for NCAPG2, we found abnormal chromosome condensation, augmented anaphase chromatin-bridge formation, and micronuclei in daughter cells of proband skin fibroblasts. To test the functional relevance of the discovered variants, we generated an ncapg2 zebrafish model. Morphants displayed clinically relevant phenotypes, such as renal anomalies, microcephaly, and concomitant increases in apoptosis and altered mitotic progression. These could be rescued by wild-type but not mutant human NCAPG2 mRNA and were recapitulated in CRISPR-Cas9 F0 mutants. Finally, we noted that the individual with a complex urogenital defect also harbored a heterozygous NPHP1 deletion, a common contributor to nephronophthisis. To test whether sensitization at the NPHP1 locus might contribute to a more severe renal phenotype, we co-suppressed nphp1 and ncapg2, which resulted in significantly more dysplastic renal tubules in zebrafish larvae. Together, our data suggest that impaired function of NCAPG2 results in a severe condensinopathy, and they highlight the potential utility of examining candidate pathogenic lesions beyond the primary disease locus.

Horizontal gene cluster transfer increased hallucinogenic mushroom diversity.

Secondary metabolites are a heterogeneous class of chemicals that often mediate interactions between species. The tryptophan-derived secondary metabolite, psilocin, is a serotonin receptor agonist that induces altered states of consciousness. A phylogenetically disjunct group of mushroom-forming fungi in the Agaricales produce the psilocin prodrug, psilocybin. Spotty phylogenetic distributions of fungal compounds are sometimes explained by horizontal transfer of metabolic gene clusters among unrelated fungi with overlapping niches. We report the discovery of a psilocybin gene cluster in three hallucinogenic mushroom genomes, and evidence for its horizontal transfer between fungal lineages. Patterns of gene distribution and transmission suggest that synthesis of psilocybin may have provided a fitness advantage in the dung and late wood-decay fungal niches, which may serve as reservoirs of fungal indole-based metabolites that alter behavior of mycophagous and wood-eating invertebrates. These hallucinogenic mushroom genomes will serve as models in neurochemical ecology, advancing the (bio)prospecting and synthetic biology of novel neuropharmaceuticals.

Drooling in Parkinson's Disease: Evidence of a Role for Divided Attention.

Drooling is a frequently reported symptom in Parkinson's Disease (PD) with significant psychosocial impact and negative health consequences including silent aspiration of saliva with the associated risk of respiratory infections. It is suggested that in PD drooling is associated with inefficient oropharyngeal swallowing which reduces the effective clearance of saliva rather than hyper-salivation. This is compounded by unintended mouth opening and flexed posture increasing anterior loss of saliva. It is reported to occur most frequently during cognitively distracting concurrent tasks suggesting an impact from divided attention in a dual-task situation. However, this supposition has not been systematically examined. This study assessed whether frequency of saliva swallows reduced, and drooling severity and frequency increased, when people with PD engaged in a cognitively distracting task. 18 patients with idiopathic PD reporting daytime drooling on the Unified Parkinson's Disease Rating Scale (UPDRS) were recruited. They completed the Radboud Oral Motor Inventory for PD saliva questionnaire and the Montreal Cognitive Assessment. UPDRS drooling score, disease stage, duration, gender, and age were recorded. Swallow frequency and drooling severity and frequency were measured at rest and during a distracting computer-based language task. There was no significant difference between drooling severity at rest and during distraction (Wilcoxon signed rank test z = - 1.724, p = 0.085). There was a significant difference between at rest and distraction conditions for both drooling frequency (Wilcoxon signed rank test z = - 2.041, p = 0.041) and swallow frequency (Wilcoxon signed rank test z = - 3.054, p = 0.002). Participants swallowed less frequently and drooled more often during the distraction task. The frequency of saliva swallows and drooling are affected by divided attention in a dual-task paradigm. Further studies are needed to explore the exact role of attention in saliva management and the clinical applications in assessment and treatment.

Differential Retention of Gene Functions in a Secondary Metabolite Cluster.

In fungi, distribution of secondary metabolite (SM) gene clusters is often associated with host- or environment-specific benefits provided by SMs. In the plant pathogen Alternaria brassicicola (Dothideomycetes), the DEP cluster confers an ability to synthesize the SM depudecin, a histone deacetylase inhibitor that contributes weakly to virulence. The DEP cluster includes genes encoding enzymes, a transporter, and a transcription regulator. We investigated the distribution and evolution of the DEP cluster in 585 fungal genomes and found a wide but sporadic distribution among Dothideomycetes, Sordariomycetes, and Eurotiomycetes. We confirmed DEP gene expression and depudecin production in one fungus, Fusarium langsethiae. Phylogenetic analyses suggested 6-10 horizontal gene transfers (HGTs) of the cluster, including a transfer that led to the presence of closely related cluster homologs in Alternaria and Fusarium. The analyses also indicated that HGTs were frequently followed by loss/pseudogenization of one or more DEP genes. Independent cluster inactivation was inferred in at least four fungal classes. Analyses of transitions among functional, pseudogenized, and absent states of DEP genes among Fusarium species suggest enzyme-encoding genes are lost at higher rates than the transporter (DEP3) and regulatory (DEP6) genes. The phenotype of an experimentally-induced DEP3 mutant of Fusarium did not support the hypothesis that selective retention of DEP3 and DEP6 protects fungi from exogenous depudecin. Together, the results suggest that HGT and gene loss have contributed significantly to DEP cluster distribution, and that some DEP genes provide a greater fitness benefit possibly due to a differential tendency to form network connections.

Assessing the Functional Role of Leptin in Energy Homeostasis and the Stress Response in Vertebrates.

Leptin is a pleiotropic hormone that plays a critical role in regulating appetite, energy metabolism, growth, stress, and immune function across vertebrate groups. In mammals, it has been classically described as an adipostat, relaying information regarding energy status to the brain. While retaining poor sequence conservation with mammalian leptins, teleostean leptins elicit a number of similar regulatory properties, although current evidence suggests that it does not function as an adipostat in this group of vertebrates. Teleostean leptin also exhibits functionally divergent properties, however, possibly playing a role in glucoregulation similar to what is observed in lizards. Further, leptin has been recently implicated as a mediator of immune function and the endocrine stress response in teleosts. Here, we provide a review of leptin physiology in vertebrates, with a particular focus on its actions and regulatory properties in the context of stress and the regulation of energy homeostasis.

Gradual caldera collapse at Bárdarbunga volcano, Iceland, regulated by lateral magma outflow.

Large volcanic eruptions on Earth commonly occur with a collapse of the roof of a crustal magma reservoir, forming a caldera. Only a few such collapses occur per century, and the lack of detailed observations has obscured insight into the mechanical interplay between collapse and eruption. We use multiparameter geophysical and geochemical data to show that the 110-square-kilometer and 65-meter-deep collapse of Bárdarbunga caldera in 2014-2015 was initiated through withdrawal of magma, and lateral migration through a 48-kilometers-long dike, from a 12-kilometers deep reservoir. Interaction between the pressure exerted by the subsiding reservoir roof and the physical properties of the subsurface flow path explain the gradual, near-exponential decline of both collapse rate and the intensity of the 180-day-long eruption.

Modeling the environmental growth of Pseudogymnoascus destructans and its impact on the white-nose syndrome epidemic.

White-nose syndrome (WNS) has had a devastating effect on North American bat populations. The causal agent of WNS is the fungal pathogen, Pseudogymnoascus destructans (Pd), which has been shown to persist in caves after the eradication of host populations. As nonpathogenic Pseudogymnoascus spp. display saprophytic growth and are among the most commonly isolated fungi from caves, we examined whether Pd could grow in cave sediments and the contribution such growth could have to WNS disease progression. We inoculated a range of diverse cave sediments and demonstrated the growth of Pd in all sediments tested. These data indicate that environmental growth of Pd could lead to the accumulation of spores above the estimated infection threshold for WNS, allowing environment-to-bat infection. The obtained growth parameters were then used in a susceptible-infected-susceptible mathematic model to determine the possible contribution of environmental Pd growth to WNS disease progression in a colony of little brown bats (Myotis lucifugus). This model suggests that the environmental growth of Pd would increase WNS infection rates, particularly in colonies experiencing longer hibernation periods or in hibernacula with high levels of organic detritus. The model also suggests that once introduced, environmental Pd growth would allow the persistence of this pathogen within infected hibernacula for decades, greatly compromising the success of bat reintroduction strategies. Together these data suggest that Pd is not reliant on its host for survival and is capable of environmental growth and amplification that could contribute to the rapid progression and long-term persistence of WNS in the hibernacula of threatened North American bats.

Plant host and soil origin influence fungal and bacterial assemblages in the roots of woody plants.

Microbial communities in plant roots provide critical links between above- and belowground processes in terrestrial ecosystems. Variation in root communities has been attributed to plant host effects and microbial host preferences, as well as to factors pertaining to soil conditions, microbial biogeography and the presence of viable microbial propagules. To address hypotheses regarding the influence of plant host and soil biogeography on root fungal and bacterial communities, we designed a trap-plant bioassay experiment. Replicate Populus, Quercus and Pinus plants were grown in three soils originating from alternate field sites. Fungal and bacterial community profiles in the root of each replicate were assessed through multiplex 454 amplicon sequencing of four loci (i.e., 16S, SSU, ITS, LSU rDNA). Soil origin had a larger effect on fungal community composition than did host species, but the opposite was true for bacterial communities. Populus hosted the highest diversity of rhizospheric fungi and bacteria. Root communities on Quercus and Pinus were more similar to each other than to Populus. Overall, fungal root symbionts appear to be more constrained by dispersal and biogeography than by host availability.

Comparison of the white-nose syndrome agent Pseudogymnoascus destructans to cave-dwelling relatives suggests reduced saprotrophic enzyme activity.

White-nose Syndrome (WNS) is an emerging infectious mycosis that has impacted multiple species of North American bats since its initial discovery in 2006, yet the physiology of the causal agent, the psychrophilic fungus Pseudogymnoascus destructans ( = Geomyces destructans), is not well understood. We investigated the ability of P. destructans to secrete enzymes that could permit environmental growth or affect pathogenesis and compared enzyme activity across several Pseudogymnoascus species isolated from both hibernating bats and cave sediments. We found that P. destructans produced enzymes that could be beneficial in either a pathogenic or saprotrophic context, such as lipases, hemolysins, and urease, as well as chitinase and cellulases, which could aid in saprotrophic growth. The WNS pathogen showed significantly lower activity for urease and endoglucanase compared to con-generic species (Pseudogymnoascus), which may indicate a shift in selective pressure to the detriment of P. destructans' saprotrophic ability. Based on the positive function of multiple saprotrophic enzymes, the causal agent of White-nose Syndrome shows potential for environmental growth on a variety of substrates found in caves, albeit at a reduced level compared to environmental strains. Our data suggest that if P. destructans emerged as an opportunistic infection from an environmental source, co-evolution with its host may have led to a reduced capacity for saprotrophic growth.