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Thalassia testudinum has undergone die-offs in the past century due to seagrass wasting disease caused by Labyrinthula sp. Little is known about how seagrasses resist Labyrinthula infections, but metabolites that inhibit Labyrinthula were previously extracted from seagrass leaves. Furthermore, leaf fungal endophytes from seagrasses possess antipathogenic potential, but their activity against Labyrinthula is unknown. Here, we aimed to identify whether fungal endophytes of T. testudinum can aid in disease defense against Labyrinthula. Through Illumina amplicon sequencing of the leaves’ mycobiome, we identified fungi that are known to produce antimicrobials. We also isolated and extracted organic compounds from endophytes to test their anti-Labyrinthula potential using disk diffusion assays. There were 22 isolates that inhibited Labyrinthula, from which two isolates, Trichoderma sp. P1a and Diaporthe sp. M14, displayed strong inhibition. LC-HRMS/MS analysis determined the likely bioactive compounds of Trichoderma as peptaibols and of Diaporthe as cytosporone B. Cytosporone B was confirmed bioactive against Labyrinthula via disk diffusion assays. While these organisms are low in abundance in the mycobiome, this study demonstrates that seagrass endophytes have the potential to play an important role in defense against Labyrinthula.

Plant microbiomes are known to serve several important functions for their host, and it is therefore important to understand their composition as well as the factors that may influence these microbial communities. The microbiome of Thalassia testudinum has only recently been explored, and studies to-date have primarily focused on characterizing the microbiome of plants in a single region. Here, we present the first characterization of the composition of the microbial communities of T. testudinum across a wide geographical range spanning three distinct regions with varying physicochemical conditions. We collected samples of leaves, roots, sediment, and water from six sites throughout the Atlantic Ocean, Caribbean Sea, and the Gulf of Mexico. We then analyzed these samples using 16S rRNA amplicon sequencing. We found that site and region can influence the microbial communities of T. testudinum, while maintaining a plant-associated core microbiome. A comprehensive comparison of available microbial community data from T. testudinum studies determined a core microbiome composed of 14 ASVs that consisted mostly of the family Rhodobacteraceae. The most abundant genera in the microbial communities included organisms with possible plant-beneficial functions, like plant-growth promoting taxa, disease suppressing taxa, and nitrogen fixers.

Onchocerca lupi (Rodonaja, 1967) is an understudied, vector-borne, filarioid nematode that causes ocular onchocercosis in dogs, cats, coyotes, wolves, and is also capable of infecting humans. Onchocercosis in dogs has been reported with increasing incidence worldwide. However, despite the growing number of reports describing canine O. lupi cases as well as zoonotic infections globally, the disease prevalence in endemic areas and vector species of this parasite remains largely unknown. Here, our study aimed to identify the occurrence of O. lupi infected dogs in northern Arizona, New Mexico, and Utah, United States and identify the vector of this nematode. A total of 532 skin samples from randomly selected companion animals with known geographic locations within the Navajo Reservation were collected and molecularly surveyed by PCR for the presence of O. lupi DNA (September 2019–June 2022) using previously published nematode primers (COI) and DNA sequencing. O. lupi DNA was detected in 50 (9.4%) sampled animals throughout the reservation. Using positive animal samples to target geographic locations, pointed hematophagous insect trapping was performed to identify potential O. lupi vectors. Out of 1,922 insects screened, 38 individual insects and 19 insect pools tested positive for the presence of O. lupi, all of which belong to the Diptera family. This increased surveillance of definitive host and biological vector/intermediate host is the first large scale prevalence study of O. lupi in companion animals in an endemic area of the United States, and identified an overall prevalence of 9.4% in companion animals as well as multiple likely biological vector and putative vector species in the southwestern United States. Furthermore, the identification of these putative vectors in close proximity to human populations coupled with multiple, local zoonotic cases highlight the One Health importance of O. lupi.

Celiac disease is an immune-mediated intestinal disorder that results from loss of oral tolerance (LOT) to dietary gluten. Reovirus elicits inflammatory Th1 cells and suppresses Treg responses to dietary antigen in a strain-dependent manner. Strain type 1 Lang (T1L) breaks oral tolerance, while strain type 3 Dearing reassortant virus (T3D-RV) does not. We discovered that intestinal infection by T1L in mice leads to the recruitment and activation of NK cells in mesenteric lymph nodes (MLNs) in a type I IFN–dependent manner. Once activated following infection, NK cells produce type II IFN and contribute to IFN-stimulated gene expression in the MLNs, which in turn induces inflammatory DC and T cell responses. Immune depletion of NK cells impairs T1L-induced LOT to newly introduced food antigen. These studies indicate that NK cells modulate the response to dietary antigen in the presence of a viral infection.

Cover crops (CC) have great potential to enhance the sustainability of agroecosystems. However, the wide range of possible rotations of CC and cash crops (CaC) means that important knowledge gaps persist on how CC affects CaC. We investigated the legacy effects of five common CC (three monocultures: vetch, melilotus, and barley, and two mixtures: barley-vetch and barley-melilotus) on two of the most important CaC, maize and wheat. A microcosm, semi-controlled experiment was established simulating warm, low-income Mediterranean conditions. After two cycles, soil physicochemical and microbial properties, as well as plant growth and nutrition variables, were measured at the CC early growth CaC stage. In maize, barley CC had the best soil microbial and nutritional legacy effects, which resulted in the highest biomass and nutrient status. In contrast, barley produced the worst results on wheat, showing the disadvantages of growing two crops from the same tribe consecutively. CC mixtures also did not offer a productive advantage over pure CC. Additionally, our findings suggest that archaea seem to play a role in increasing N and Zn content in maize shoots. Furthermore, shoot B contents showed highly significant regressions with the CaC biomass. These results can help select the appropriate CC in each case.

Legumes provide important benefits in rotations. Interseeding cover crops (CCs) allows an additional legume CC in case of a short window after the main crop. However, legume input level and management could modify the expected benefits. In a Mediterranean irrigated agroecosystem, we evaluated the responses of topsoil (0–10 cm) and early maize development to increasing legume CC input in a biannual maize–wheat rotation under traditional tillage (TT; CC incorporated) and minimum tillage (MT; CC rolled-crimped). In the third year, at two early maize stages, we tested three legume input levels: (i) R0, non-CC; (ii) R1, barley–vetch CC; (iii) R2, vetch interseeded into maize in addition to the CC mixture. Overall, MT enhanced soil properties, but frequently conditioned to legume input level. The tillage system affected R1 the most, with MTR1 showing the better overall soil response while TTR0 showed the poorest. MTR2 was the best combination for early maize development, but not for soil health. Moreover, a better overall soil health did not lead to a better early maize performance in the short term. In this alkaline soil, CC favored early maize growth, whereas mycorrhization, enhanced under TT, favored crop nutrition. Increased legume input under MT should be monitored to avoid negative effects in soil in the mid–long term.

OBJECTIVES/GOALS: As hospitals across the nation respond to the need to address community violence, there is a dearth of Hospital-based Violence Intervention Programs (HVIPs) in the South despite having disproportionate rates. This research aims to identify key factors and strategies for implementation of an HVIP among rural patient populations in a southern state. METHODS/STUDY POPULATION: Semi-structured interviews will be conducted with medical providers, social service organizations, and patients transferred from four high-risk rural areas in Arkansas. Data will be analyzed using Framework Analysis, a rapid analysis approach involving framework development, code application, impactful statement identification, and content analysis. Evidence- Based Quality Improvement (EBQI), a group consensus making process, will be conducted to identify key implementation strategies and factors to adapt based interview findings. Priority areas for adaptation will be identified via systematic rating. The EBQI team, including researchers and key rural stakeholders will engage in a series of discussion, vote on final strategies, and develop a guide for future HVIP implementation and pilot testing. RESULTS/ANTICIPATED RESULTS: Findings from this study will result in a prioritized list of barriers and facilitators across sample groups. Factors will be rated by level of importance. Cluster maps will display the relationships among factors. Go and no-go zones will be identified based on importance and feasibility. Implementation strategies will be mapped to barriers and facilitators. DISCUSSION/SIGNIFICANCE: The findings will result in a culturally and geographically relevant HVIP model and package of implementation strategies to test in future hybrid trials (feasibility pilot & multi-site RCT); and shape the future of violence prevention efforts in healthcare settings across the rural South.

Onchocerca lupi is a filarial nematode that causes ocular onchocercosis in canines globally including North America and areas of Europe, North Africa, and the Middle East. Reported incidence of this parasite in canines has continued to steadily escalate since the early 21st century and was more recently documented in humans. Whole genome sequencing (WGS) of this parasite can provide insight into gene content, provide novel surveillance targets, and elucidate the origin and range expansion. However, past attempts of whole genome sequencing of other Onchocerca species reported a substantial portion of their data unusable due to the variable over-abundance of host DNA in samples. Here, we have developed a method to determine the host-to-parasite DNA ratio using a quantitative PCR (qPCR) approach that relies on two standard plasmids each of which contains a single copy gene specific to the parasite genus Onchocerca (major body wall myosin gene, myosin) or a single copy gene specific to the canine host (polycystin-1 precursor, pkd1). These plasmid standards were used to determine the copy number of the myosin and pkd1 genes within a sample to calculate the ratio of parasite and host DNA. Furthermore, whole genome sequence (WGS) data for three O. lupi isolates were consistent with our host-to-parasite DNA ratio results. Our study demonstrates, despite unified DNA extraction methods, variable quantities of host DNA within any one sample which will likely affect downstream WGS applications. Our quantification assay of host-to-parasite genome copy number provides a robust and accurate method of assessing canine host DNA load in an O. lupi specimen that will allow informed sample selection for WGS. This study has also provided the first whole genome draft sequence for this species. This approach is also useful for future focused WGS studies of other parasites.

Cover crops (CC) promote soil health, but the termination method can condition the benefits for soil microorganisms. In a greenhouse experiment, we evaluated the legacy effects of four common CC termination methods on mycorrhization, soil microbial abundance, structure, and activity, as well as other soil properties, and its interaction with water levels (well-watered and water deficit). Mowing and residue incorporation (INC), glyphosate (GLY), roller crimper (ROL) and glyphosate + roller crimper (RGL) were evaluated, together with no CC, at two sampling dates of a subsequent maize. The water level modulated the soil microbial response to CC termination methods, especially in the glyphosate methods. Legacy effects on soil microbial attributes were notable and evolved differently from maize, from pre-emergence to ~3 months later. At final sampling, INC showed the best microbial response at both water levels, enhancing most microbial attributes. ROL was the second most beneficial method, especially in well-watered soil, promoting fungi but nullifying the CC positive effect on bacteria. Regardless of water level, GLY and RGL showed a similar microbial response. In well-watered soil, GLY and RGL had a negative effect on the total fungi, which separated the RGL response from the ROL. Overall, the time since CC termination and water level modulated the soil microbial response to the termination methods. Further research is needed to investigate CC termination impacts under different environmental conditions, in order to better understand the processes involved and provide farm-level recommendations.

Abstract Background Design thinking is a problem-solving framework that has been used to enhance patient experiences, improve clinical outcomes, and refine medical curricula. This study reviewed the use of design thinking in health professions education. Methods A search yielded 169 articles, which were excluded if they were: (1) not related to education; (2) lacking an application of design thinking; or (3) not associated with healthcare. The final review yielded 15 articles, which were analyzed using qualitative methods. Results All articles were published in 2009 or later and were diverse in their context, participants, and approach. Six studies emphasized the early stages of design thinking, with inspiration and ideation stages fostered through a variety of activities, such as lectures, small group discussions, and workshops. Studies examined a range of outcomes, including self-efficacy, perceptions, and solutions to a specific problem. Conclusions Our findings raise important considerations for health professions education, including the extent to which we should: 1) teach design thinking to students as a skill-based tool to prepare students for problem solving in complex healthcare environments; and 2) use design thinking to create, implement, and refine health professions curricula and educational programs. Despite the apparent benefits of design thinking, many questions for health professions education remain.

The ERK1/2 signaling pathway promotes myelin wrapping during development and remyelination, and sustained ERK1/2 activation in the oligodendrocyte (OL) lineage results in hypermyelination of the CNS. We therefore hypothesized that increased ERK1/2 signaling in the OL lineage would 1) protect against immune-mediated demyelination due to increased baseline myelin thickness and/or 2) promote enhanced remyelination and thus functional recovery after experimental autoimmune encephalomyelitis (EAE) induction. Cnp-Cre;Mek1DD-eGFP/+ mice that express a constitutively active form of MEK1 (the upstream activator of ERK1/2) in the OL lineage, exhibited a significant decrease in EAE clinical severity compared to controls. However, experiments using tamoxifen-inducible Plp-Cre ERT ;Mek1DD-eGFP/+ or Pdgfrα-Cre ERT ;Mek1DD-eGFP mice revealed this was not solely due to a protective or reparative effect resulting from MEK1DD expression specifically in the OL lineage. Because EAE is an immune-mediated disease, we examined Cnp-Cre ; Mek1DD-eGFP/+ splenic immune cells for recombination. Surprisingly, GFP + recombined CD19 + B-cells, CD11b + monocytes, and CD3 + T-cells were noted when Cre expression was driven by the Cnp promoter. While ERK1/2 signaling in monocytes and T-cells is associated with proinflammatory activation, fewer studies have examined ERK1/2 signaling in B-cell populations. After in vitro stimulation, MEK1DD-expressing B-cells exhibited a 3-fold increase in CD138 + plasmablasts and a 5-fold increase in CD5 + CD1d hi B-cells compared to controls. Stimulated MEK1DD-expressing B-cells also exhibited an upregulation of IL-10, known to suppress the initiation of EAE when produced by CD5 + CD1d hi regulatory B-cells. Taken together, our data support the conclusion that sustained ERK1/2 activation in B-cells suppresses immune-mediated demyelination via increasing activation of regulatory B10 cells.

Planktonic microbial communities mediate many vital biogeochemical processes in wetland ecosystems, yet compared to other aquatic ecosystems, like oceans, lakes, rivers or estuaries, they remain relatively underexplored. Our study site, the Florida Everglades (USA)—a vast iconic wetland consisting of a slow-moving system of shallow rivers connecting freshwater marshes with coastal mangrove forests and seagrass meadows—is a highly threatened model ecosystem for studying salinity and nutrient gradients, as well as the effects of sea level rise and saltwater intrusion. This study provides the first high-resolution phylogenetic profiles of planktonic bacterial and eukaryotic microbial communities (using 16S and 18S rRNA gene amplicons) together with nutrient concentrations and environmental parameters at 14 sites along two transects covering two distinctly different drainages: the peat-based Shark River Slough (SRS) and marl-based Taylor Slough/Panhandle (TS/Ph). Both bacterial as well as eukaryotic community structures varied significantly along the salinity gradient. Although freshwater communities were relatively similar in both transects, bacterioplankton community composition at the ecotone (where freshwater and marine water mix) differed significantly. The most abundant taxa in the freshwater marshes include heterotrophic Polynucleobacter sp. and potentially phagotrophic cryptomonads of the genus Chilomonas, both of which could be key players in the transfer of detritus-based biomass to higher trophic levels.

Cover crops (CC) provide important ecosystem services that are demanded to achieve more sustainable agrosystems. However, the legacy effects of CC on the microbial community structure and its interactions with the subsequent cash crops (CaC) are still poorly understood, especially when CC mixtures are involved. In this work, five CC (3 monocultures and 2 mixtures) were selected in an experiment under semi-controlled conditions to investigate if CC monocultures and mixtures differed in their effects on soil and crop variables and if the identity of the subsequent crop modulates these effects. The two most consumed crops worldwide, wheat and maize, were sown separately after CC. The legacy effects of CC on the studied microbial variables largely depended on the interaction with the CaC. The vetch and the barley-vetch mixture stood out by providing the microbial conditions that enhanced the absorption of macro- and micronutrients, to finally seek the highest wheat biomass (>80% more than the control). In maize, the effects of CC on soil microbiota were more limited. The soil microbial responses for CC mixtures were complex and contrasting. In wheat, the barley-vetch mixture behaved like barley monoculture, whereas in maize, this mixture behaved like vetch monoculture. In both CaC, the barley-melilotus mixture differed completely from its monocultures, mainly through changes in archaea, Glomeromycota, and F:B ratio. Therefore, it is necessary to deepen the knowledge on the CC-CaC-microbial interactions to select the CC that most enhance the sustainability and yield of each agrosystem.

The Florida Keys, a delicate archipelago of sub-tropical islands extending from the south-eastern tip of Florida, host the vast majority of the only coral barrier reef in the continental United States. Abiotic as well as microbial components of the surrounding waters are pivotal for the health of reef habitats, and thus could play an important role in understanding the development and transmission of coral diseases in Florida. In this study, we analyzed microbial community structure and abiotic factors in waters around the Florida Reef Tract. Both bacterial and eukaryotic community structure were significantly linked with variations in temperature, dissolved oxygen, and total organic carbon values. High abundances of copiotrophic bacteria as well as several potentially harmful microbes, including coral pathogens, fish parasites and taxa that have been previously associated with Red Tide and shellfish poisoning were present in our datasets and may have a pivotal impact on reef health in this ecosystem.

Introduction Training for the clinical research workforce does not sufficiently prepare workers for today’s scientific complexity; deficiencies may be ameliorated with training. The Enhancing Clinical Research Professionals’ Training and Qualifications developed competency standards for principal investigators and clinical research coordinators. Methods Clinical and Translational Science Awards representatives refined competency statements. Working groups developed assessments, identified training, and highlighted gaps. Results Forty-eight competency statements in 8 domains were developed. Conclusions Training is primarily investigator focused with few programs for clinical research coordinators. Lack of training is felt in new technologies and data management. There are no standardized assessments of competence.

Introduction The translation of discoveries to drugs, devices, and behavioral interventions requires well-prepared study teams. Execution of clinical trials remains suboptimal due to varied quality in design, execution, analysis, and reporting. A critical impediment is inconsistent, or even absent, competency-based training for clinical trial personnel. Methods In 2014, the National Center for Advancing Translational Science (NCATS) funded the project, Enhancing Clinical Research Professionals’ Training and Qualifications (ECRPTQ), aimed at addressing this deficit. The goal was to ensure all personnel are competent to execute clinical trials. A phased structure was utilized. Results This paper focuses on training recommendations in Good Clinical Practice (GCP). Leveraging input from all Clinical and Translational Science Award hubs, the following was recommended to NCATS: all investigators and study coordinators executing a clinical trial should understand GCP principles and undergo training every 3 years, with the training method meeting the minimum criteria identified by the International Conference on Harmonisation GCP. Conclusions We anticipate that industry sponsors will acknowledge such training, eliminating redundant training requests. We proposed metrics to be tracked that required further study. A separate task force was composed to define recommendations for metrics to be reported to NCATS.

Insulin antibodies are detectable in the sera of most patients within 3-4 months of starting treatment with conventional bovine insulins. Various factors determine the immunogenicity of insulin preparations including the genetic background of the recipient. This causes wide variation in response. Solid phase absorption studies as well as competitive binding in fluid phase indicate that the antibodies formed are almost always specific for determinants shared by the endogenous human molecule. This has important implications for the metabolic effect of insulin antibodies in vivo as well as for mechanisms of autoantibody production in man. [ABSTRACT FROM AUTHOR]

Abstract Introduction Transgender patients experience poor health outcomes and often avoid seeking medical care because of negative encounters with providers. Despite growing awareness of the health disparities transgender patients face, there is very little curricular time in medical schools to improve medical students’ knowledge and skills for caring for transgender patients. This standardized patient (SP) case was developed for use in a communication challenges workshop for advanced clerkship students in order to address working with transgender patients. Methods This formative SP encounter takes place in a classroom as part of a half-day workshop on communication challenges with patients. We developed the case to focus specifically on skills related to obtaining patients’ preferred names and pronouns, as well as taking an appropriate patient history. Materials for SP recruitment, SP training, and case implementation are included within this publication. Results In preliminary uses of the case, 80% of students (N = 64) agreed or strongly agreed that it had increased their skills for working with transgender patients. Observational data from the debrief discussions also revealed that medical students perceived gaps in their medical training regarding LGBT health and expressed interest in their program incorporating more information on transgender health. Discussion This case adds to a growing number of curricular interventions to address medical students’ knowledge and skills with regard to lesbian, gay, bisexual, and transgender (LGBT) patients and, as a result, aims to address health disparities in LGBT patient populations.

Seagrasses are vital members of coastal systems, which provide several important ecosystem services such as improvement of water quality, shoreline protection, and serving as shelter, food, and nursery to many species, including economically important fish. They also act as a major carbon sink and supply copious amounts of oxygen to the ocean. A decline in seagrasses has been observed worldwide, partly due to climate change, direct and indirect human activities, diseases, and increased sulfide concentrations in the coastal porewaters. Several studies have shown a symbiotic relationship between seagrasses and their microbiome. For instance, the sulfur, nitrogen, and carbon cycles are important biochemical pathways that seem to be linked between the plant and its microbiome. The microbiome presumably also plays a key role in the health of the plant, for example in oxidizing phyto-toxic sulfide into non-toxic sulfate, or by providing protection for seagrasses from pathogens. Two of the most abundant seagrasses in Florida include Thalassia testudinum (turtle grass) and Syringodium filliforme (manatee grass), yet there is little data on the composition of the microbiome of these two genera. In this study, the microbial composition of the phyllosphere and rhizosphere of Thalassia testudinum and Syringodium filiforme were compared to water and sediment controls using amplicon sequencing of the V4 region of the 16S rRNA gene. The microbial composition of the leaves, roots, seawater, and sediment differ from one another, but are similar between the two species of seagrasses.

Lichens are symbiotic associations of fungi with microalgae and/or cyanobacteria, which are considered among the slowest growing organisms, with strong tolerance to adverse environmental conditions. There are about 400 genera and 1600 species of lichens and those belonging to the Usnea genus comprise about 360 of these species. Usnea lichens have been used since ancient times as dyes, cosmetics, preservatives, deodorants and folk medicines. The phytochemistry of the Usnea genus includes more than 60 compounds which belong to the following classes: depsides, depsidones, depsones, lactones, quinones, phenolics, polysaccharides, fatty acids and dibenzofurans. Due to scarce knowledge of metabolomic profiles of Usnea species (U. barbata, U. antarctica, U. rubicunda and U. subfloridana), a study based on UHPLC-ESI-OT-MS-MS was performed for a comprehensive characterization of their secondary metabolites. From the methanolic extracts of these species a total of 73 metabolites were identified for the first time using this hyphenated technique, including 34 compounds in U. barbata, 21 in U. antarctica, 38 in U. rubicunda and 37 in U. subfloridana. Besides, a total of 13 metabolites were not identified and reported so far, and could be new according to our data analysis. This study showed that this hyphenated technique is rapid, effective and accurate for phytochemical identification of lichen metabolites and the data collected could be useful for chemotaxonomic studies.

Seagrass meadows are ecologically and economically important components of many coastal areas worldwide. Ecosystem services provided by seagrasses include reducing the number of microbial pathogens in the water, providing food, shelter and nurseries for many species, and decreasing the impact of waves on the shorelines. A global assessment reported that 29% of the known areal extent of seagrasses has disappeared since seagrass areas were initially recorded in 1879. Several factors such as direct and indirect human activity contribute to the demise of seagrasses. One of the main reasons for seagrass die-offs all over the world is increased sulfide concentrations in the sediment that result from the activity of sulfate-reducing prokaryotes, which perform the last step of the anaerobic food chain in marine sediments and reduce sulfate to H2S. Recent seagrass die-offs, e.g., in the Florida and Biscayne Bays, were caused by an increase in pore-water sulfide concentrations in the sediment, which were the combined result of unfavorable environmental conditions and the activities of various groups of heterotrophic bacteria in the sulfate-rich water-column and sediment that are stimulated through increased nutrient concentrations. Under normal circumstances, seagrasses are able to withstand low levels of sulfide, probably partly due to microbial symbionts, which detoxify sulfide by oxidizing it to sulfur or sulfate. Novel studies are beginning to give greater insights into the interactions of microbes and seagrasses, not only in the sulfur cycle. Here, we review the literature on the basic ecology and biology of seagrasses and focus on studies describing their microbiome.

ObjectiveTo explore the association of a functional germline variant in the 3'-UTR of KRAS with endometrial cancer risk, as well as the association of microRNA (miRNA) signatures and the KRAS-variant with clinical characteristics and survival outcomes in two prospective RTOG endometrial cancer trials.Methods/materialsThe association of the KRAS-variant with endometrial cancer risk was evaluated by case-control analysis of 467 women with type 1 or 2 endometrial cancer and 582 age-matched controls. miRNA and DNA were isolated for expression profiling and genotyping from tumor specimens of 46 women with type 1 endometrial cancer enrolled in RTOG trials 9708 and 9905. miRNA expression levels and KRAS-variant genotype were correlated with patient and tumor characteristics, and survival outcomes were evaluated by variant allele type.ResultsThe KRAS-variant was not significantly associated with overall endometrial cancer risk (14% controls and 17% type 1 cancers), although was enriched in type 2 endometrial cancers (24%, p = 0.2). In the combined analysis of RTOG 9708/9905, miRNA expression differed by age, presence of lymphovascular invasion and KRAS-variant status. Overall survival rates at 3 years for patients with the variant and wild-type alleles were 100% and 77% (HR 0.3, p = 0.24), respectively, favoring the variant.ConclusionsThe KRAS-variant may be a genetic marker of risk for type 2 endometrial cancers. In addition, tumor miRNA expression appears to be associated with patient age, lymphovascular invasion and the KRAS-variant, supporting the hypothesis that altered tumor biology can be measured by miRNA expression, and that the KRAS-variant likely impacts endometrial tumor biology.

The author offers information on how to avoid deep brain stimulation (DBS) failures in Tourette syndrome (TS). He mentions that DBS surgery has been an effetive treatment for basal ganglia disorders and obsessive-compulsive disorder. Details concerning the potential DBS failures in TS is presented, followed by discussion on the importance of Servello report in adressing DBS failures.

Competing Interests: The authors declare that the editorial was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. DE declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

We developed Multivariate Adaptive Regression Splines (MARS) machine learning models of chronic stressors using the Pregnancy Risk Assessment Monitoring System data (2012-2017) to predict preterm birth (PTB) more accurately and identify chronic stressors driving PTB among non-Hispanic (N-H) Black and N-H White pregnant women in the U.S. We trained the MARS models using 5-fold cross-validation, whose performance was evaluated with AUC. We computed variable importance for PTB prediction. Our models showed high accuracy (AUC: 0.754-0.765). The number of prenatal care visits, premature rupture of membrane, and medical conditions were the most important variables in predicting PTB across the populations. Chronic stressors (e.g., low maternal education and violence) and their correlates were pivotal for PTB prediction only for N-H Black women. Interpretable, race/ethnicity-specific MARS models can predict PTB accurately and explain the most impactful life stressors and their magnitude of effect on PTB risk among N-H Black and N-H White women.

Background: Posttraumatic stress disorder (PTSD) is a common sequela to military sexual trauma (MST) among women veterans. Yoga has shown promise in research examining its benefit for symptoms and sequela of PTSD., Aims: The objective of this study was to evaluate the feasibility of a randomized controlled trial (RCT) of Trauma Center Trauma-Sensitive Yoga (TCTSY) for women veterans with PTSD related to MST., Method: In this feasibility study, the final sample included women veterans ( n = 41) with PTSD related to MST accessing health care in a Veterans Affairs Health Care System in the southeast United States; the majority were African American ( n = 33; 80.5%). Interventions used established protocols of 10 weekly sessions of group TCTSY versus 12 weekly sessions of group Cognitive Processing Therapy (CPT). PTSD was assessed via clinical interview and participant report. Additional data collection included multiple participant-reported outcomes commonly associated with PTSD and psychophysiological measures. We also collected data regarding participant satisfaction and feasibility-related feedback from participants and providers., Results: Feasibility and acceptability were evaluated via demand, practicality, fidelity, and acceptability. This was measured by expressed interest, attendance, program completion, barriers to care and satisfaction with treatment, and satisfaction with interventions and data collection., Conclusions: Results indicate the RCT design and TCTSY implementation were feasible; a full-scale RCT was subsequently conducted to determine efficacy of the experimental intervention. Recommendations for successful research strategies are provided., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. DisclaimerThe contents of this article do not represent the views of the U.S. Department of Veterans Affairs or the U.S. Government or the Agency for Healthcare Research and Quality. All authors approved this manuscript and this submission. The authors report no conflicts of interest.

Introduction: Psychological distress symptoms (symptoms of depression, anxiety, and posttraumatic stress) are common following stillbirth. Black women who experience stillbirth are less likely to seek support than White women, consistent with the strong Black woman (SBW) construct, which expects Black women to tolerate stress and trauma gracefully, without seeking help., Methods: In this cross-sectional study we sought to determine the relative contributions of SBW belief, perceived lack of social support, and culturally relevant coping behaviors to psychological distress symptoms in Black women bereaved by stillbirth. We partnered with a stillbirth support organization to recruit a sample of 91 Black women bereaved by stillbirth in the 3 years prior to study participation. The online study survey measured SBW belief, culturally relevant coping behaviors, perceived social support, and psychological distress symptoms along with sociodemographics, pregnancy history, and stillbirth characteristics. We used stepwise selection in multiple linear regression to determine the relative contributions of SBW belief, perceived social support, and coping behaviors to measures of psychological distress symptoms in our sample., Results: Higher SBW belief, lower perceived social support, and higher collective coping (coping behaviors involving other people) were associated with increases in all 3 measures of psychological distress symptoms, controlling for age and other traumatic events., Discussion: Further understanding of the influence of SBW belief on Black women's psychological distress following stillbirth may assist with the development of culturally appropriate interventions to mitigate psychological distress symptoms in this group., (© 2023 by the American College of Nurse‐Midwives.)

Description: The U.S. Department of Veterans Affairs (VA) and Department of Defense (DoD) worked together to revise the 2017 VA/DoD Clinical Practice Guideline for the Management of Posttraumatic Stress Disorder and Acute Stress Disorder. This article summarizes the 2023 clinical practice guideline (CPG) and its development process, focusing on assessments and treatments for which evidence was sufficient to support a recommendation for or against., Methods: Subject experts from both departments developed 12 key questions and reviewed the published literature after a systematic search using the PICOTS (population, intervention, comparator, outcomes, timing of outcomes measurement, and setting) method. The evidence was then evaluated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. Recommendations were made after consensus was reached; they were based on quality and strength of evidence and informed by other factors, including feasibility and patient perspectives. Once the draft was peer reviewed by an external group of experts and their inputs were incorporated, the final document was completed., Recommendations: The revised CPG includes 34 recommendations in the following 5 topic areas: assessment and diagnosis, prevention, treatment, treatment of nightmares, and treatment of posttraumatic stress disorder (PTSD) with co-occurring conditions. Six recommendations on PTSD treatment were rated as strong. The CPG recommends use of specific manualized psychotherapies over pharmacotherapy; prolonged exposure, cognitive processing therapy, or eye movement desensitization and reprocessing psychotherapy; paroxetine, sertraline, or venlafaxine; and secure video teleconferencing to deliver recommended psychotherapy when that therapy has been validated for use with video teleconferencing or when other options are unavailable. The CPG also recommends against use of benzodiazepines, cannabis, or cannabis-derived products. Providers are encouraged to use this guideline to support evidence-based, patient-centered care and shared decision making to optimize individuals' health outcomes and quality of life., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-2757.

A clinical practice guideline (CPG) is a rigorously established set of recommendations based on currently available evidence about the efficacy, safety, acceptability, and feasibility of interventions to assist with clinical decision-making. The 2023 Department of Veterans Affairs /Department of Defense Clinical Practice Guideline for Management of Posttraumatic Stress Disorder and Acute Stress Disorder is described herein. The CPG recommendations are accompanied by a clinical algorithm, which incorporates principles of evidence-based practice, shared decision-making, and functional and contextual assessments of goals and outcomes. An overview of the CPG recommendations is combined with a discussion of questions that clinicians and patients may face in implementing the CPG and suggestions for how to effectively work with the CPG., (© 2024 International Society for Traumatic Stress Studies.)

Clinical dashboards are an emerging and fast-evolving technology used to support frontline clinicians' practice. Understanding end users' perceived engagement with clinical dashboards is essential to co-design, implementation, and adoption. There is a lack of literature exploring the integration of dashboards into clinical workflow. This rapid review explores clinical end users' perceived engagement with dashboards that support workflow. We conducted a literature search in PubMed and CINAHL. Four articles met our eligibility criteria. Findings reveal variations in taxonomy and measures used to evaluate clinicians' perceived engagement. There are also a variety of reported barriers and facilitators to adoption. Standardized frameworks and vocabulary are needed to facilitate a common understanding of clinical end users' perceived engagement with dashboards.

Background: An intersectional approach to health research provides an analytical foundation to explain the multidimensionality of health status, resource accessibility, privilege, oppression, and current and historical context. The use of intersectionality in health research has known limitations. Its use in health-related fields too often focuses on outcomes, such as health disparities, rather than processes, such as power structures and social determinants., Objective: This scoping review serves to examine how intersectionality has been implemented by nurses in the peer-reviewed literature. We offer insight into how it may be incorporated to inform future nursing research and healthcare provision., Design & Methods: Systematic searches of PubMed ( n = 257), SCOPUS ( n = 807), EMBASE ( n = 396), CINAHL ( n = 224), and Health Source: Nursing and Academics ( n = 491), published since the seminal publication on intersectionality (1989 - 2023), identified 131 research articles that met inclusion and exclusion criteria. Data extraction and synthesis were used to describe the breadth and depth of the literature specific to the application of intersectionality in nursing research., Results: The included studies used intersectionality to examine the intersections of numerous identities, such as race, gender, and immigration status. However, most studies were descriptive/observational in nature, underreported their methods, and conducted deficit-based research instead of strength-based inquiries. Of note, the vast majority of included articles were published within the last five years., Conclusions: Future researchers using intersectionality as a framework can improve their approach by reporting clear definitions and operationalization of intersectionality. Observational science dominated the included studies; future research should focus on intervention development and evaluation using an intersectional lens. Lastly, caution should be placed on research that focuses solely on deficits among marginalized communities, which places scientists at risk of perpetuating stereotypes or enhancing already-existing stigmas., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Objectives: In this pragmatic clinical trial, the primary objective is to increase access to behavioral treatment of urinary incontinence (UI) for women Veterans by comparing the effectiveness of two virtual care delivery modalities., Methods: Veterans Affairs (VA) clinical sites in AL, GA, NC will virtually randomize 286 women Veterans with UI (ie, stress, urge, or mixed). We will compare the effectiveness of our mHealth UI application (MyHealtheBladder) to a single VA Video Connect (VVC) session delivered by trained UI providers. Women without improvement after 8 weeks will receive an optimization VVC visit using a sequential, multiple assignment, randomized trial (SMART) design. The primary outcome is UI symptom improvement at 12-weeks with or without optimization; secondary outcomes include improvements in lower urinary tract symptoms, adherence, retention rates, perceptions of improvement, and visit-related miles saved. Sample size needed to identify a 2.5-point change (range 0-21) in the International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form (ICIQ-UI SF) from baseline to 12-weeks post-randomization is 200 participants. Allowing for an attrition rate of 25%, 286 participants are required., Key Results: Study team initiated remote recruitment on April 2020. Recruitment is on target with a 75% retention rate. We expect completion in fall of 2023 (clinicaltrials.govNCT04237753)., Discussion/conclusion: Engaging women Veterans with virtual modalities for initial UI treatment may increase access to UI care while also improving symptoms. After assessing efficacy, adherence, and retention, the next step is to implement the most effective option for remote delivery of evidence-based behavioral UI treatment for women Veterans., Trial Registration: ClinicalTrials.gov number NCT04237753., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

The retinal pigmented epithelium (RPE) constitutes the outer blood-retinal barrier, enables photoreceptor function of the eye, and is constantly exposed to oxidative stress. As such, dysfunction of the RPE underlies pathology leading to development of age-related macular degeneration (AMD), the leading cause of vision loss among the elderly in industrialized nations. A major responsibility of the RPE is to process photoreceptor outer segments, which relies on the proper functioning of its endocytic pathways and endosomal trafficking. Exosomes and other extracellular vesicles (EVs) from RPE are an essential part of these pathways and may be early indicators of cellular stress. To test the role of small EVs (sEVs) including exosomes, that may underlie the early stages of AMD, we used a polarized primary RPE cell culture model under chronic subtoxic oxidative stress. Unbiased proteomic analyses of highly purified basolateral sEVs from oxidatively stressed RPE cultures revealed changes in proteins involved in epithelial barrier integrity. There were also significant changes in proteins accumulating in the basal-side sub-RPE extracellular matrix during oxidative stress, that could be prevented with an inhibitor of sEV release. Thus, chronic subtoxic oxidative stress in primary RPE cultures induces changes in sEV content, including basal-side specific desmosome and hemidesmosome shedding via sEVs. These findings provide novel biomarkers of early cellular dysfunction and opportunity for therapeutic intervention in age-related retinal diseases (e.g., AMD)., Competing Interests: Declaration of Interest Statement We confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.