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Abstract Traditionally, bacteriostatic antibiotics are agents able to arrest bacterial growth. Despite being traditionally viewed as unable to kill bacterial cells, when they are used clinically the outcome of these drugs is frequently as effective as when a bactericidal drug is used. We explore the dynamics of Escherichia coli after exposure to two ribosome-targeting bacteriostatic antibiotics, chloramphenicol and azithromycin, for thirty days. The results of our experiments provide evidence that bacteria exposed to these drugs replicate, evolve, and generate a sub-population of small colony variants (SCVs) which are resistant to multiple drugs. These SCVs contribute to the evolution of heteroresistance and rapidly revert to a susceptible state once the antibiotic is removed. Stated another way, exposure to bacteriostatic drugs selects for the evolution of heteroresistance in populations previously lacking this trait. More generally, our results question the definition of bacteriostasis as populations exposed to bacteriostatic drugs are replicating despite the lack of net growth.

This article examines how workers describe their motivations for participation in the platform-based gig economy, particularly as rideshare and delivery drivers. I investigate how these accounts vary by socioeconomic class, gender, and race. Based on interviews conducted as part of the American Voices Project, I find that workers’ accounts differ based on income and gender. Higher earners tend to downplay financial needs and describe platform work as a path to explore their larger community, whereas lower earners focus on financial needs and benefits. Additionally, among lower earners, explanations differed by gender. Interestingly, I did not find any differences based on race. I conclude by investigating why workers from different social groups might offer varying accounts.

Abstract Extracellular vesicles (EVs), particles enriched in bioactive molecules like proteins, nucleic acids, and lipids, are crucial mediators of intercellular communication and play key roles in various physiological and pathological processes. EVs have been shown to be involved in ovarian follicular function and to be altered in two prevalent gynecological disorders; polycystic ovarian syndrome (PCOS) and endometriosis. Ovarian follicles are complex microenvironments where folliculogenesis takes place with well-orchestrated interactions between granulosa cells, oocytes, and their surrounding stromal cells. Recent research unveiled the presence of EVs, including exosomes and microvesicles, in the follicular fluid (FFEVs), which constitutes part of the developing oocyte’s microenvironment. In the context of PCOS, a multifaceted endocrine, reproductive, and metabolic disorder, studies have explored the dysregulation of these FFEVs and their cargo. Nine PCOS studies were included in this review and two miRNAs were commonly reported in two different studies, miR-379 and miR-200, both known to play a role in female reproduction. Studies have also demonstrated the potential use of EVs as diagnostic tools and treatment options. Endometriosis, another prevalent gynecological disorder characterized by ectopic growth of endometrial-like tissue, has also been linked to aberrant EV signaling. EVs in the peritoneal fluid of women with endometriosis carry molecules that modulate the immune response and promote the establishment and maintenance of endometriosis lesions. EVs derived from endometriosis lesions, serum and peritoneal fluid obtained from patients with endometriosis showed no commonly reported biomolecules between the eleven reviewed studies. Importantly, circulating EVs have been shown to be potential biomarkers, also reflecting the severity of the pathology. Understanding the interplay of EVs within human ovarian follicles may provide valuable insights into the pathophysiology of both PCOS and endometriosis. Targeting EV-mediated communication may open avenues for novel diagnostic and therapeutic approaches for these common gynecological disorders. More research is essential to unravel the mechanisms underlying EV involvement in folliculogenesis and its dysregulation in PCOS and endometriosis, ultimately leading to more effective and personalized interventions.

Objective: Robotic thoracic surgery provides another minimally invasive approach in addition to video-assisted thoracoscopic surgery (VATS) that yields less pain and faster recovery compared with open surgery. However, robotic incisions are generally placed more inferiorly, which may increase the risk of intercostal nerve injury that affects the abdominal wall. We hypothesized that a robotic approach causes greater ipsilateral rectus muscle atrophy compared with open and VATS approaches. Methods: The cross-sectional area and density of bilateral rectus abdominis muscles were measured on computed tomography scans in patients who underwent lobectomy in 2018. The differences between the contralateral and ipsilateral muscles were compared between preoperative and 6-month surveillance scans. Changes were compared among the open, VATS, and robotic approaches through a mixed effects model after adjustments of correlation and covariates. Results: Of 99 lobectomies, 25 (25.3%) were open, 56 (56.6%) VATS, and 18 (18.1%) robotic. The difference between the contralateral and ipsilateral rectus muscle cross-sectional area was significantly larger at 6 months after robotic surgery compared with open (31.4% vs 9.5%, P = .049) and VATS (31.4% vs 14.1%, P = .021). There were no significant differences in the cross-sectional area between the open and VATS approach. Conclusions: In this retrospective analysis, there was greater ipsilateral rectus muscle atrophy associated with robotic thoracic surgery compared with open or VATS approaches. These findings should be correlated with clinical symptoms and followed to assess for resolution or persistence.

Microstructurally flexible high entropy alloys (HEAs) can be tailored for strength via dual-phase strengthening mechanisms, which originate from the strain-induced phase transformation microstructural phenomena. One such alloy is a recently synthesized Fe42Mn28Co10Cr15Si5 (at%) HEA consisting of metastable gamma austenite (γ), stable epsilon martensite (ε), and stable sigma (σ) phases. In this work, a crystal plasticity homogenization incorporating a physically based phase transformation and hardening models is used to interpret and better understand the effects of strain induced phase transformation phenomena on the overall hardening response of the alloy. The transformation model is conceived based on the grain-scale stress sensitive motion of partial dislocations forming shear bands, while the hardening model is an extended Kocks-Mecking-type dislocation density-based formulation sensitive to grain size and shape. The deformation of constituent grains per phase in the alloy is modeled as a combination of anisotropic elasticity, crystallographic glide, and γ→ε phase transformation. Parameters of the hardening and transformation models within the homogenization are calibrated and validated on a suite of data including flow stress curves and phase fractions measured under compression, while the corresponding texture evolution data is used solely for verification. Good predictions of the model elucidate that the transformation induced dynamic Hall-Petch-type barrier effect is the primary origin of strain hardening along with the increase in the ε-phase fraction and dislocation density, while the individual strength of the phases gives rise to the overall strength. The modeling framework described in the present work is expected to be applicable to other HEA systems.

We designed 60% thick airfoil to improve the aerodynamic performance in the root region of wind turbine rotor blades, taking into account current constraints. After an extensive literature review and patent research, a design methodology (including the considerations of simple manufacturing) was set up, and extensive 2D- and 3D-CFD investigations with four codes (Xfoil, MSES, ANSYS fluent, and DLR-tau) were performed, including implementation inside a generic 10 MW test-blade (CIG10MW). Comparison with results from Blade Element Momentum (BEM) methods and the estimation of 3D effects due to the rotating blade were undertaken. One specific shape (with a pronounced flat-back) was selected and tested in the Deutsche WindGuard aeroacoustic Wind Tunnel (DWAA), in Bremerhaven, Germany. A total of 34 polars were measured, included two trailing edge shapes and aerodynamic devices such as vortex generators, gurney flaps, zig-zag tape, and a splitter plate. Considerable changes in lift and drag characteristics were observed due to the use of aerodynamic add-ons. With the studies presented here, we believe we have closed an important technological gap.

Abstract Background Severe COVID-19 is uncommon, restricted to 19% of the total population. In response to the first virus wave (alpha variant of SARS-CoV-2), we investigated whether a biomarker indicated severity of disease and, in particular, if variable expression of angiotensin converting enzyme 2 (ACE2) in blood might clarify this difference in risk and of post COVID -19 conditions (PCC). Methods The IRB-approved study compared patients hospitalized with severe COVID-19 to healthy controls. Severe infection was defined requiring oxygen or increased oxygen need from baseline at admission with positive COVID-19 PCR. A single blood sample was obtained from patients within a day of admission. ACE2 RNA expression in blood cells was measured by an RT-PCR assay. Plasma ACE1 and ACE2 enzyme activities were quantified by fluorescent peptides. Plasma TIMP-1, PIIINP and MMP-9 antigens were quantified by ELISA. Data were entered into REDCap and analyzed using STATA v 14 and GraphPad Prism v 10. Results Forty-eight patients and 72 healthy controls were recruited during the pandemic. ACE2 RNA expression in peripheral blood mononuclear cells (PBMC) was rarely detected acutely during severe COVID-19 but common in controls (OR for undetected ACE2: 12.4 [95% CI: 2.62-76.1]). ACE2 RNA expression in PBMC did not determine plasma ACE1 and ACE2 activity, suggesting alternative cell-signaling pathways. Markers of fibrosis (TIMP-1 and PIIINP) and vasculopathy (MMP-9) were additionally elevated. ACE2 RNA expression during severe COVID-19 often responded within hours to convalescent plasma. Analogous to oncogenesis, we speculate that potent, persistent, cryptic processes following COVID-19 (the renin-angiotensin system (RAS), fibrosis and vasculopathy) initiate or promote post-COVID-19 conditions (PCC) in susceptible individuals. Conclusions This work elucidates biological and temporal plausibility for ACE2, TIMP1, PIIINP and MMP-9 in the pathogenesis of PCC. Intersection of these independent systems is uncommon and may in part explain the rarity of PCC.

Abstract High altitude (HA) ascent imposes systemic hypoxia and associated risk of acute mountain sickness. Acute hypoxia elicits a hypoxic ventilatory response (HVR), which is augmented with chronic HA exposure (i.e., ventilatory acclimatization; VA). However, laboratory‐based HVR tests lack portability and feasibility in field studies. As an alternative, we aimed to characterize area under the curve (AUC) calculations on Fenn diagrams, modified by plotting portable measurements of end‐tidal carbon dioxide (PETCO2) against peripheral oxygen saturation (SpO2) to characterize and quantify VA during incremental ascent to HA (n = 46). Secondarily, these participants were compared with a separate group following the identical ascent profile whilst self‐administering a prophylactic oral dose of acetazolamide (Az; 125 mg BID; n = 20) during ascent. First, morning PETCO2 and SpO2 measurements were collected on 46 acetazolamide‐free (NAz) lowland participants during an incremental ascent over 10 days to 5160 m in the Nepal Himalaya. AUC was calculated from individually constructed Fenn diagrams, with a trichotomized split on ranked values characterizing the smallest, medium, and largest magnitudes of AUC, representing high (n = 15), moderate (n = 16), and low (n = 15) degrees of acclimatization. After characterizing the range of response magnitudes, we further demonstrated that AUC magnitudes were significantly smaller in the Az group compared to the NAz group (P = 0.0021), suggesting improved VA. These results suggest that calculating AUC on modified Fenn diagrams has utility in assessing VA in large groups of trekkers during incremental ascent to HA, due to the associated portability and congruency with known physiology, although this novel analytical method requires further validation in controlled experiments. Highlights What is the central question of this study? What are the characteristics of a novel methodological approach to assess ventilatory acclimatization (VA) with incremental ascent to high altitude (HA)? What is the main finding and its importance? Area under the curve (AUC) magnitudes calculated from modified Fenn diagrams were significantly smaller in trekkers taking an oral prophylactic dose of acetazolamide compared to an acetazolamide‐free group, suggesting improved VA. During incremental HA ascent, quantifying AUC using modified Fenn diagrams is feasible to assess VA in large groups of trekkers with ascent, although this novel analytical method requires further validation in controlled experiments.

There is recognition in the field of emergency medicine (EM) that social determinants of health (SDoH) are key drivers of patient care outcomes. Leaders in EM are calling for curricula integrating SDoH assessment and intervention, public health, and multidisciplinary approaches to EM care throughout medical school and residency. This intersection of SDoH and the emergency care system is known as social emergency medicine (SEM). Currently, there are few resources available for EM training programs to integrate this content; as a result, few EM trainees receive adequate education in SEM. To address this gap, we developed a four-part training in SEM tailored to EM residency programs and medical schools. This curriculum, known as RISE-EM (Resident Instruction in Social Emergency Medicine), uses video lectures, case examples, and group discussions to engage trainees and develop competency in providing sound care that is grounded in evidence-based principles of SEM. In the current study, we tested RISE-EM by delivering the video lectures to residents and medical students in two training programs. We administered pre- and post-course knowledge tests and a post-course participant attitudes survey to assess the acceptability and potential efficacy of the program for improving SEM knowledge and attitudes among EM learners. We found it to be both feasible and acceptable to introduce SEM content in residency conferences, with preliminary data showing statistically significant improvement in knowledge of the content and self-efficacy to apply it to their clinical practice. In summary, RISE-EM has been highly valued by EM learners and viewed as a strong supplement to their existing training, and it has been shown to successfully improve SEM knowledge and attitudes.

Abstract Background Depression and anxiety are significant contributors to the global burden of disease among young people. Accurate data on the prevalence of these conditions are crucial for the equitable distribution of resources for planning and implementing effective programs. This study aimed to culturally adapt and validate data collection tools for measuring depression and anxiety at the population level. Methods The study was conducted in Kathmandu, Nepal, a diverse city with multiple ethnicities, languages, and cultures. Ten focus group discussions with 56 participants and 25 cognitive interviews were conducted to inform adaptations of the Patient Health Questionnaire adapted for Adolescents (PHQ-A) and Generalized Anxiety Disorder (GAD-7). To validate the tools, a cross-sectional survey of 413 adolescents (aged 12–19) was conducted in three municipalities of Kathmandu district. Trained clinical psychologists administered the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-DSM 5 version) to survey participants. Results A number of cultural adaptations were required, such as changing statements into questions, using a visual scale (glass scale) to maintain uniformity in responses, and including a time frame at the beginning of each item. For younger adolescents aged 12 to 14 years, a PHQ-A cut-off of > = 13 had a sensitivity of 0.93, specificity of 0.80, positive predictive value (PPV) of 0.33, and negative predictive value (NPV) of 0.99. For older adolescents aged 15–19, a cut-off of > = 11 had a sensitivity of 0.89, specificity of 0.70, PPV of 0.32, and NPV of 0.97. For GAD-7, a cut-off of > = 8 had a sensitivity of 0.70 and specificity of 0.67 for younger adolescents and 0.71 for older adolescents, with a PPV of 0.39 and NPV of 0.89. The individual symptom means of both PHQ-A and GAD-7 items showed moderate ability to discriminate between adolescents with and without depression and anxiety. Conclusion The PHQ-A and GAD-7 demonstrate fair psychometric properties for screening depression but performed poorly for anxiety, with high rates of false positives. Even when using clinically validated cut-offs, population prevalence rates would be inflated by 2–4 fold with these tools, requiring adjustment when interpreting epidemiological findings.

Abstract Psychological interventions delivered by non-specialist providers have shown mixed results for treating maternal depression. mHealth solutions hold the possibility for unobtrusive behavioural data collection to identify challenges and reinforce change in psychological interventions. We conducted a proof-of-concept study using passive sensing integrated into a depression intervention delivered by non-specialists to twenty-four adolescents and young mothers (30% 15–17 years old; 70% 18–25 years old) with infants (

Abstract The biological mechanisms underlying the onset of major depressive disorder (MDD) have predominantly been studied in adult populations from high-income countries, despite the onset of depression typically occurring in adolescence and the majority of the world’s adolescents living in low- and middle-income countries (LMIC). Taking advantage of a unique adolescent sample in an LMIC (Brazil), this study aimed to identify biological pathways characterizing the presence and increased risk of depression in adolescence, and sex-specific differences in such biological signatures. We collected blood samples from a risk-stratified cohort of 150 Brazilian adolescents (aged 14–16 years old) comprising 50 adolescents with MDD, 50 adolescents at high risk of developing MDD but without current MDD, and 50 adolescents at low risk of developing MDD and without MDD (25 females and 25 males in each group). We conducted RNA-Seq and pathway analysis on whole blood. Inflammatory-related biological pathways, such as role of hypercytokinemia/hyperchemokinemia in the pathogenesis of influenza (z-score = 3.464, p

Abstract Background Depression is a prevalent mental health condition worldwide but there is limited data on its presentation and associated symptoms in primary care settings in low- and middle-income countries like Nepal. This study aims to assess the prevalence of depression, its hallmark and other associated symptoms that meet the Diagnostic and Statistical Manual (DSM-5) criteria in primary healthcare facilities in Nepal. The collected information will be used to determine the content of a mobile app-based clinical guidelines for better detection and management of depression in primary care. Methods A total of 1,897 adult patients aged 18–91 (63.1% women) attending ten primary healthcare facilities in Jhapa, a district in eastern Nepal, were recruited for the study between August 2, 2021, and March 25, 2022. Trained research assistants conducted face-to-face interviews in private spaces before the consultation with healthcare providers. Depression symptoms, including hallmark symptoms, was assessed using the validated Nepali version of the Patient Health Questionnaire (PHQ-9). Results One in seven (14.5%) individuals attending primary health care facilities in Jhapa met the threshold for depression based on a validated cut-off score ( > = 10) on the PHQ-9. The most commonly reported depressive symptoms were loss of energy and sleep difficulties. Approximately 25.4% of women and 18.9% of men endorsed at least one of the two hallmark symptoms on the PHQ-9. Using a DSM-5 algorithm (at least one hallmark symptom and five or more total symptoms) to score the PHQ-9, 6.3% of women and 4.3% of men met the criteria for depression. The intra-class correlation coefficient for PHQ-9 total scores by health facility as the unit of clustering was 0.01 (95% confidence interval, 0.00-0.04). Conclusion Depression symptoms are common among people attending primary healthcare facilities in Nepal. However, the most common symptoms are not the two hallmark criteria. Use of total scores on a screening tool such as the PHQ-9 risks overestimating the prevalence and generating false positive diagnoses. Compared to using cut off scores on screening tools, training health workers to first screen for hallmark criteria may increase the accuracy of identification and lead to better allocation of treatment resources.

Abstract Background Autism spectrum disorder has been linked to a variety of organizational and developmental deviations in the brain. One such organizational difference involves hemispheric lateralization, which may be localized to language-relevant regions of the brain or distributed more broadly. Methods In the present study, we estimated brain hemispheric lateralization in autism based on each participant’s unique functional neuroanatomy rather than relying on group-averaged data. Additionally, we explored potential relationships between the lateralization of the language network and behavioral phenotypes including verbal ability, language delay, and autism symptom severity. We hypothesized that differences in hemispheric asymmetries in autism would be limited to the language network, with the alternative hypothesis of pervasive differences in lateralization. We tested this and other hypotheses by employing a cross-sectional dataset of 118 individuals (48 autistic, 70 neurotypical). Using resting-state fMRI, we generated individual network parcellations and estimated network asymmetries using a surface area-based approach. A series of multiple regressions were then used to compare network asymmetries for eight significantly lateralized networks between groups. Results We found significant group differences in lateralization for the left-lateralized Language (d = -0.89), right-lateralized Salience/Ventral Attention-A (d = 0.55), and right-lateralized Control-B (d = 0.51) networks, with the direction of these group differences indicating less asymmetry in autistic males. These differences were robust across different datasets from the same participants. Furthermore, we found that language delay stratified language lateralization, with the greatest group differences in language lateralization occurring between autistic males with language delay and neurotypical individuals. Conclusions These findings evidence a complex pattern of functional lateralization differences in autism, extending beyond the Language network to the Salience/Ventral Attention-A and Control-B networks, yet not encompassing all networks, indicating a selective divergence rather than a pervasive one. Moreover, we observed an association between Language network lateralization and language delay in autistic males.

Abstract Species–environment relationships have been extensively explored through species distribution models (SDM) and species abundance models (SAM), which have become key components to understand the spatial ecology and population dynamics directed at biodiversity conservation. Nonetheless, within the internal structure of species' ranges, habitat suitability and species abundance do not always show similar patterns, and using information derived from either SDM or SAM could be incomplete and mislead conservation efforts. We gauged support for the abundance–suitability relationship and used the combined information to prioritize the conservation of South American dwarf caimans (Paleosuchus palpebrosus and P. trigonatus). We used 7 environmental predictor sets (surface water, human impact, topography, precipitation, temperature, dynamic habitat indices, soil temperature), 2 regressions methods (Generalized Linear Models—GLM, Generalized Additive Models—GAM), and 4 parametric distributions (Binomial, Poisson, Negative binomial, Gamma) to develop distribution and abundance models. We used the best predictive models to define four categories (low, medium, high, very high) to plan species conservation. The best distribution and abundance models for both Paleosuchus species included a combination of all predictor sets, except for the best abundance model for P. trigonatus which incorporated only temperature, precipitation, surface water, human impact, and topography. We found non‐consistent and low explanatory power of environmental suitability to predict abundance which aligns with previous studies relating SDM‐SAM. We extracted the most relevant information from each optimal SDM and SAM and created a consensus model (2,790,583 km2) that we categorized as low (39.6%), medium (42.7%), high (14.9%), and very high (2.8%) conservation priorities. We identified 279,338 km2 where conservation must be critically prioritized and only 29% of these areas are under protection. We concluded that optimal models from correlative methods can be used to provide a systematic prioritization scheme to promote conservation and as surrogates to generate insights for quantifying ecological patterns.

Biosecurity measures preventing exposure of pigs to rodents, wildlife, and contaminated feed or waste products reduce the risk of zoonotic Trichinella infection in pork. To understand the benefits of such measures in the United States, we conducted the first comprehensive survey of pigs produced under the Pork Quality Assurance Plus production standard, surveying 3,208,643 pork samples from twelve processing locations tested over a period of 54 months. We detected no Trichinella sp. positives in any of these pork samples, providing a 95% confidence in a Trichinella sp. prevalence of

ABSTRACT Diarrheal diseases with infectious etiology remain a major cause of death globally, particularly in low-income countries. Entamoeba histolytica is a pathogenic protozoan parasite that is the causative agent of amebiasis. Amebiasis has a wide presentation in clinical severity with many factors, including the bacterial microbiota, contributing to this variation. The innate immune response also plays a critical role in regulating the severity of E. histolytica infection, with neutrophils reported to have a protective role. Despite this, the precise mechanism of how neutrophils mediate amebic killing is poorly understood. Thus, modern platforms that allow for inquiry of granulocyte–ameba interactions will increase our understanding of this disease. Herein, we describe an assay for neutrophil killing of E. histolytica by utilizing high-dimensional spectral flow cytometry. Neutrophils were isolated from wild-type 5-week-old C57BL/6 mice and co-cultured with E. histolytica at various multiplicity of infections (MOIs). After co-culture, neutrophils and E. histolytica were stained for spectral flow cytometry. Cell populations were identified using surface markers and fluorescence minus one (FMO) controls. We have previously shown that animals colonized with a component of the human microbiota, Clostridium scindens, were protected from E. histolytica. This protection was associated with elevated neutrophil count. Here, we explored amebic killing capacity and observed that neutrophils from animals with C. scindens possessed heightened amebic killing compared with controls. Thus, this study establishes a novel platform that can provide an in-depth analysis of granulocyte–parasite interactions in various contexts, including during alteration of the intestinal microbiota.IMPORTANCEThe tools for studying host immune cell–E. histolytica interactions are limited. Factors, such as parasite heterogeneity, infectivity, and difficulties with culture systems and animal models, make interrogation of these interactions challenging. Thus, Entamoeba researchers can benefit from next-generation models that allow for the analysis of both host and parasite cells. Here, we demonstrate the use of a novel platform that allows for the determination of parasite–host cell interactions and customizable high-dimensional phenotyping of both populations. Indeed, spectral flow cytometry can approach >40 markers on a single panel and can be paired with custom-developed parasite antibodies that can be conjugated to fluorochromes via commercially available kits. This platform affords researchers the capability to test highly precise hypotheses regarding host–parasite interactions.

Background: Postpartum depression (PPD) is a common experience among mothers worldwide. Family members, especially husbands, can play an integral role in supporting and helping mothers recover from PPD. However, husbands are typically not included in interventions to address postpartum depression among women. This study explored husbands’ perspectives on engaging in a counseling intervention augmented with a digital health component for the treatment of PPD. Methods: A convergent mixed methods design was used to evaluate husbands’ attitudes and involvement in a counseling and digital intervention for mothers in a semi-urban region of Nepal.Thematic analysis of semi-structured interviews was used to derive emergent themes. A joint display examined differences in themes for husbands whose wives experienced a significant decline in PPD symptoms as measured by the Patient Health Questionnaire-9 pre and post intervention, as compared to husbands of women whose symptoms stayed the same or worsened. Results: Thirteen husbands were interviewed. Three primary themes emerged: the impact of gender norms and attitudes on engagement in the intervention, involvement and support in the intervention, and suggestions for future interventions for PPD. Among wives who experienced a reduction in depression symptoms, their husbands were more likely to endorse gender-equitable norms and attitudes and the husbands provided emotional support, as well as participating in household chores and childcare. Conclusion: When husbands are living in the same household, providing support and being involved in their wives’ PPD treatment can help them recover. Husbands describe time at home and work as barriers to being able to help their wives. PPD interventions that involve husbands might need to educate husbands about how they can provide emotional support to their partner.

Relapsing fever (RF), a vector-borne disease caused by Borrelia spp., is characterized by recurring febrile episodes due to repeated bouts of bacteremia. RF spirochetes can be geographically and phylogenetically divided into two distinct groups; Old World RF Borrelia (found in Africa, Asia, and Europe) and New World RF Borrelia (found in the Americas). While RF is a rarely reported disease in the Americas, RF is prevalent in endemic parts of Africa. Despite phylogenetic differences between Old World and New World RF Borrelia and higher incidence of disease associated with Old World RF spirochete infection, genetic manipulation has only been described in New World RF bacteria. Herein, we report the generation of genetic tools for use in the Old World RF spirochete, Borrelia duttonii. We describe methods for transformation and establish shuttle vector- and integration-based approaches for genetic complementation, creating green fluorescent protein (gfp)-expressing B. duttonii strains as a proof of principle. Allelic exchange mutagenesis was also used to inactivate a homolog of the Borrelia burgdorferi p66 gene, which encodes an important virulence factor, in B. duttonii and demonstrate that this mutant was attenuated in a murine model of RF. Finally, the B. duttonii p66 mutant was complemented using shuttle vector- and cis integration-based approaches. As expected, complemented p66 mutant strains were fully infectious, confirming that P66 is required for optimal mammalian infection. The genetic tools and techniques reported herein represent an important advancement in the study of RF Borrelia that allows for future characterization of virulence determinants and colonization factors important for the enzootic cycle of Old World RF spirochetes.

Background The use of feedback to address gaps and reinforce skills is a key component of successful competency-based mental health and psychosocial support intervention training approaches. Competency-based feedback during training and supervision for personnel delivering psychological interventions is vital for safe and effective care. Aims For non-specialists trained in low-resource settings, there is a lack of standardised feedback systems. This study explores perspectives on competency-based feedback, using structured role-plays that are featured on the Ensuring Quality in Psychosocial and Mental Health Care (EQUIP) platform developed by the World Health Organization and United Nations Children’s Fund. Method Qualitative data were collected from supervisors, trainers and trainees from multiple EQUIP training sites (Ethiopia, Kenya, Lebanon, Peru and Uganda), from 18 key informant interviews and five focus group discussions (N = 41 participants). Qualitative analysis was conducted in Dedoose, using a codebook with deductively and inductively developed themes. Results Four main themes demonstrated how a competency-based structure enhanced the feedback process: (a) competency-based feedback was personalised and goal-specific, (b) competency-based feedback supported a feedback loop, (c) competency-based feedback supported a comfortable and objective feedback environment, and (d) competency-based feedback created greater opportunities for flexibility in training and supervision. Conclusions A better understanding of the role of feedback supports the implementation of competency-based training that is systematic and effective for trainers and supervisors, which ultimately benefits the learning process for trainees.

Background: Although deep brain stimulation (DBS) has established uses for patients with movement disorders and epilepsy, it is under consideration for a wide range of neurologic and neuropsychiatric conditions. Objective: To review successful and unsuccessful DBS clinical trials and identify factors associated with early trial termination. Methods: The ClinicalTrials.gov database was screened for all studies related to DBS. Information regarding condition of interest, study aim, trial design, trial success, and, if applicable, reason for failure was collected. Trials were compared and logistic regression was utilized to identify independent factors associated with trial termination. Results: Of 325 identified trials, 79.7% were successful and 20.3% unsuccessful. Patient recruitment, sponsor decision, and device issues were the most cited reasons for termination. 242 trials (74.5%) were interventional with 78.1% successful. There was a statistically significant difference between successful and unsuccessful trials in number of funding sources (p = 0.0375). NIH funding was associated with successful trials while utilization of other funding sources (academic institutions and community organizations) was associated with unsuccessful trials. 83 trials (25.5%) were observational with 84.0% successful; there were no statistically significant differences between successful and unsuccessful observational trials. Conclusion: One in five clinical trials for DBS were found to be unsuccessful, most commonly due to patient recruitment difficulties. The source of funding was the only factor associated with trial success. As DBS research continues to grow, understanding the current state of clinical trials will help design successful future studies, thereby minimizing futile expenditures of time, cost, and patient engagement.

Abdominal aortic aneurysm (AAA) is a significant source of mortality worldwide and carries a mortality of greater than 80% after rupture. Despite extensive efforts to develop pharmacological treatments, there is currently no effective agent to prevent aneurysm growth and rupture. Current treatment paradigms only rely on the identification and surveillance of small aneurysms, prior to ultimate open surgical or endovascular repair. Recently, regenerative therapies have emerged as promising avenues to address the degenerative changes observed in AAA. This review briefly outlines current clinical management principles, characteristics, and pharmaceutical targets of AAA. Subsequently, a thorough discussion of regenerative approaches is provided. These include cellular approaches (vascular smooth muscle cells, endothelial cells, and mesenchymal stem cells) as well as the delivery of therapeutic molecules, gene therapies, and regenerative biomaterials. Lastly, additional barriers and considerations for clinical translation are provided. In conclusion, regenerative approaches hold significant promise for in situ reversal of tissue damages in AAA, necessitating sustained research and innovation to achieve successful and translatable therapies in a new era in AAA management.

Allelic variation at the Ptprc gene, which encodes the pan-leukocyte marker CD45/Ly5, is commonly exploited to track hematopoietic reconstitution by flow cytometry in mixed bone marrow chimera transplant experiments. Historically, this was accomplished using bone marrow from C57BL/6 (Ptprcb/CD45.2/Ly5.2) and congenic B6.SJL-PtprcaPepcb/Boy (Ptprca/CD45.1/Ly5.1) mice. Recently, the Jackson Laboratory directly CRISPR-engineered the Ptprca allele in C57BL/6J mice. This new isogenic strain, termed JAXBoy, differs from wild-type C57BL/6J mice by two nucleotides, compared to the biologically significant 37 megabase (Mb) SJL interval retained in B6.SJL-PtprcaPepcb/Boy/J mice. Currently, Ptprc/CD45 variants are identified by flow cytometry or allele-specific real-time PCR, both of which require specialized workflows and equipment compared to standard genotyping of endpoint PCR products by gel electrophoresis. Here, we employed allele-specific oligonucleotides in conjunction with differential incorporation of a long non-specific oligo 5′-tail to allow for simultaneous identification of the Ptprca and Ptprcb alleles using endpoint PCR and gel electrophoresis. This method allows for integration of Ptprc genotyping into standard genotyping workflows, which use a single set of thermocycling and gel electrophoresis conditions. Importantly, the strategy of primer placement and tail addition described here can be adapted to discriminate similar single- or multi-nucleotide polymorphisms at other genomic loci.

BackgroundThere are limited treatment options available to improve the prognosis of patients with advanced or metastatic cholangiocarcinoma particularly intrahepatic cholangiocarcinoma (iCCA). This study aimed to evaluate the efficacy and safety of combining chemotherapy plus anti-PD-1/L1 drugs compared to chemotherapy alone in advanced, unresectable, and recurrent intrahepatic cholangiocarcinoma patients.MethodsPatients with advanced, unresectable, or recurrent iCCA who received chemotherapy combined with PD-1/PD-L1 inhibitors or chemotherapy alone were retrospectively screened and analyzed. The primary outcomes were overall survival (OS) and progression-free survival (PFS). The secondary outcomes were overall response rate (ORR), disease control rate (DCR), and safety.Results81 eligible patients were included in the study (chemotherapy plus anti-PD-1/L1 group n=51, and chemotherapy-alone group n=30). The median OS was 11 months for the chemotherapy plus anti-PD-1/L1 group, significantly longer than the 8 months in the chemotherapy-alone group, with a hazard ratio (HR) of 0.53 (95% CI 0.30–0.94, P = 0.008). The median PFS of 7 months in the chemotherapy plus anti-PD-1/L1 group was significantly longer than the 4 months in the chemotherapy-alone group, with HR of 0.48 (95% CI 0.27–0.87); P = 0.002). Similarly, the combined therapy group showed a higher ORR (29.4%) and DCR (78.4%) compared to 13.3% and 73.3% in the chemotherapy-alone group, respectively. More grade 3–4 treatment-related adverse effects were recorded in the chemotherapy plus anti-PD-1/L1 group (66.7%) compared to the chemotherapy-alone group (23.3%), however, they were manageable and tolerable.ConclusionChemotherapy plus anti-PD-1/L1 represents a more effective and tolerable treatment option for advanced, unresectable, and recurrent iCCA patients compared to chemotherapy alone.

IntroductionBecause Genomic selection (GS) is a predictive methodology, it needs to guarantee high-prediction accuracies for practical implementations. However, since many factors affect the prediction performance of this methodology, its practical implementation still needs to be improved in many breeding programs. For this reason, many strategies have been explored to improve the prediction performance of this methodology.MethodsWhen environmental covariates are incorporated as inputs in the genomic prediction models, this information only sometimes helps increase prediction performance. For this reason, this investigation explores the use of feature engineering on the environmental covariates to enhance the prediction performance of genomic prediction models.Results and discussionWe found that across data sets, feature engineering helps reduce prediction error regarding only the inclusion of the environmental covariates without feature engineering by 761.625% across predictors. These results are very promising regarding the potential of feature engineering to enhance prediction accuracy. However, since a significant gain in prediction accuracy was observed in only some data sets, further research is required to guarantee a robust feature engineering strategy to incorporate the environmental covariates.

Abstract Background An integrated practice unit (IPU) that provides a multidisciplinary approach to patient care, typically involving a primary care provider, registered nurse, social worker, and pharmacist has been shown to reduce healthcare utilization among high-cost super-utilizer (SU) patients or multi-visit patients (MVP). However, less is known about differences in the impact of these interventions on insured vs. uninsured SU patients and super high frequency SUs ( $$\ge$$ 8 ED visits per 6 months) vs. high frequency SUs (4–7 ED visits per 6 months). Methods We assessed the percent reduction in ED visits, ED cost, hospitalizations, hospital days, and hospitalization costs following implementation of an IPU for SUs located in an academic tertiary care facility. We compared outcomes for publicly insured with uninsured patients, and super high frequency SUs with high frequency SUs 6 months before vs. 6 months after enrollment in the IPU. Results There was an overall 25% reduction in hospitalizations (p

Abstract Although mostly considered distinct, conspiracy mentality and paranoia share conceptual similarities (e.g., persecutory content, resistance to disconfirming evidence). Using self-report data from a large and multinational online sample (N = 2510; from the UK, the US, Hong Kong, Germany, and Australia), we examined whether paranoia and conspiracy mentality represent distinct latent constructs in exploratory and confirmatory factor analyses. Utilising network analysis, we then explored common and unique correlates of paranoia and conspiracy mentality while accounting for their shared variance. Across sites, paranoia and conspiracy mentality presented distinct, yet weakly correlated (r = 0.26), constructs. Both were associated with past traumatic experiences, holding negative beliefs about the self and other people, sleep problems, and a tendency to worry. However, paranoia was related to increased negative affect (i.e., anxiety) and decreased social support, whereas the opposite pattern was observed for conspiracy mentality (i.e., decreased anxiety and depression, increased social support). Paranoia and conspiracy mentality are related but not the same constructs. Their similar and distinct correlates point to common and unique risk factors and underlying mechanisms.

Objective: Failure to rescue (FTR), defined as in-hospital death following a major complication, has been increasingly studied in patients who undergo cardiothoracic surgery. This study tested the hypothesis that elderly patients undergoing lung cancer resection have greater rates of FTR compared with younger patients. Methods: Patients who underwent surgery for primary lung cancer between 2011 and 2020 and had at least 1 major postoperative complication were identified using the National Surgical Quality Improvement Program database. Patients who died following complications (FTR) were compared with those who survived in an elderly (80+ years) and younger (

Background: Radiotherapy (RT) is integral to breast cancer treatment, especially in the current era that emphasizes breast conservation. The aim of our study was to determine the incidence of subsequent primary lung cancer after RT exposure for breast cancer over a time span of 3 decades to quantify this risk over time as modern oncologic treatment continues to evolve. Methods: The SEER (Surveillance, Epidemiology, and End Results) database was queried from 1988 to 2014 for patients diagnosed with nonmetastatic breast cancer. Patients who subsequently developed primary lung cancer were identified. Multivariable regression modeling was performed to identify independent factors associated with the development of lung cancer stratified by follow up intervals of 5 to 9 years, 10 to 15 years, and >15 years after breast cancer diagnosis. Results: Of the 612,746 patients who met our inclusion criteria, 319,014 (52%) were irradiated. primary lung cancer developed in 5556 patients (1.74%) in the RT group versus 4935 patients (1.68%) in the non-RT group. In a multivariable model stratified by follow-up duration, the overall HR of developing subsequent ipsilateral lung cancer in the RT group was 1.14 (P = .036) after 5 to 9 years of follow-up, 1.28 (P = .002) after 10 to 15 years of follow-up, and 1.30 (P = .014) after >15 years of follow-up. The HR of contralateral lung cancer was not increased at any time interval. Conclusions: The increased risk of developing a primary lung cancer secondary to RT exposure for breast cancer is much lower than previously published. Modern RT techniques may have contributed to the improved risk profile, and this updated study is important for counseling and surveillance of breast cancer patients.

ABSTRACTThis research aimed to develop nanosuspensions as carriers of Annona muricata acetogenins (ACGs) using different concentrations of soy lecithin (SL), hydroxypropyl-β-cyclodextrin (βCD) and the dispersion method (low agitation, middle agitation and ultrasound) on particle size and polydispersity index (PDI). A response surface analysis was performed to find an optimized, validated and characterized nanosuspension (OβCDSL-ACGs-NSps) and to measure its antibacterial activity. The best conditions to formulate OβCDSL-ACGs-NSps with spherical nanoparticles (133.77 nm), PDI (0.20) and good stability (−37 mV) were 10 mg/mL SL, 0.16% βCD and ultrasound as a dispersion method. Nanoparticles from OβCDSL-ACGs-NSps exhibited a high entrapment (85.33%) and encapsulation efficiency (56.09%). The highest release (84.15%) of ACGs was observed until 36 h. OβCDSL-ACGs-NSps also showed significant antibacterial inhibition against E. faecalis (87%) and L. monocytogenes (75%) at 320 µg/mL. βCDSL-ACGs-NSps is an attractive and promising alternative to improve the solubility and bioavailability of ACGs in pharmaceutical applications.

Proteins are localized and concentrated at cellular and genomic locations for specific and efficient functions. Efforts to understand protein accumulation in eukaryotic organisms have primarily focused on multivalent interactions between intrinsically disordered regions (IDRs) as mediators of protein condensation. We previously showed that α-crystalline domain (ACD) proteins 15 (ACD15) and 21 (ACD21) were required for multimerization and the accumulation of gene-silencing methyl-CpG-binding domain protein 6 (MBD6) at chromocenters in Arabidopsis thaliana. Here, we demonstrate that ACDs and IDRs can act as parallel mechanisms, facilitating higher-order MBD6 assemblies. Using human IDRs known to be important for protein accumulation, we replicated and enhanced the accumulation of MBD6 at chromocenters. In addition, IDRs fused to MBD6 could substitute for ACD function and partially reconstitute the MBD6 gene-silencing function. However, the accumulation of MBD6 by IDRs still required ACD15 and ACD21 for full effect. These results establish that ACD-mediated protein accumulation is a mechanism that can function similarly to and together with IDR-mediated mechanisms.

This study aimed to comprehensively analyze inflammatory and autoimmune characteristics of patients with sickle cell disease (SCD) at a steady-state condition (StSt) compared to healthy controls (HCs) to explore the pathogenesis of StSt and its impact on patients’ well-being. The study cohort consisted of 40 StSt participants and 23 HCs enrolled between July 2021 and April 2023. StSt participants showed elevated white blood cell (WBC) counts and altered hematological measurements when compared to HCs. A multiplex immunoassay was used to profile 80 inflammatory cytokines/chemokines/growth factors in plasma samples from these SCD participants and HCs. Significantly higher plasma levels of 35 analytes were observed in SCD participants, with HGF, IL-18, IP-10, and MCP-2 being among the most significantly affected analytes. Additionally, autoantibody profiles were also altered, with elevated levels of anti-SSA/Ro60, anti-Ribosomal P, anti-Myeloperoxidase (MPO), and anti-PM/Scl-100 observed in SCD participants. Flow cytometric analysis revealed higher rates of red blood cell (RBC)/reticulocyte-leukocyte aggregation in SCD participants, predominantly involving monocytes. Notably, correlation analysis identified associations between inflammatory mediator levels, autoantibodies, RBC/reticulocyte-leukocyte aggregation, clinical lab test results, and pain crisis/sensitivity, shedding light on the intricate interactions between these factors. The findings underscore the potential significance of specific biomarkers and therapeutic targets that may hold promise for future investigations and clinical interventions tailored to the unique challenges posed by SCD. In addition, the correlations between vaso-occlusive crisis (VOC)/pain/sensory sensitivity and inflammation/immune dysregulation offer valuable insights into the pathogenesis of SCD and may lead to more targeted and effective therapeutic strategies.Clinical Trial RegistrationClinicalTrials.gov, Identifier: NCT05045820.

Older Black men are underrepresented in research despite being disproportionately affected by Alzheimer’s disease (AD) and cardiovascular (CV) risk factors related to AD compared with non-Hispanic Whites. Although dietary interventions have shown promise to reduce modifiable CV risk factors related to AD, Black Americans have lower adherence likely due to lack of cultural considerations. Using a noninterventional convergent parallel mixed-methods approach, this study examined the cultural contexts that inform perceptions of dietary interventions among older Midwestern Black men. All participants completed an online demographic and dietary habit survey prior to focus group discussions. Two focus group discussion sessions were conducted with a total of 10 cognitively normal Black men aged 55 years and older. Survey data were analyzed using a frequency analysis and qualitative data were analyzed using a six-step thematic analysis process. Most men indicated having hypertension ( N = 7, 77.8%) and currently not following a dietary eating pattern ( N = 8, 88.9%). Emerging themes identified included (1) knowledge of dementia, (2) perceptions of dietary interventions, (3) barriers impacting participation in dietary interventions, and (4) overcoming barriers to engage Black men in dietary interventions. Findings from this study should inform the design of future dietary interventions for AD prevention to enhance participation among older Black men.

Abstract The respiratory syncytial virus polymerase complex, consisting of the polymerase (L) and phosphoprotein (P), catalyzes nucleotide polymerization, cap addition, and cap methylation via the RNA dependent RNA polymerase, capping, and Methyltransferase domains on L. Several nucleoside and non-nucleoside inhibitors have been reported to inhibit this polymerase complex, but the structural details of the exact inhibitor-polymerase interactions have been lacking. Here, we report a non-nucleoside inhibitor JNJ-8003 with sub-nanomolar inhibition potency in both antiviral and polymerase assays. Our 2.9 Å resolution cryo-EM structure revealed that JNJ-8003 binds to an induced-fit pocket on the capping domain, with multiple interactions consistent with its tight binding and resistance mutation profile. The minigenome and gel-based de novo RNA synthesis and primer extension assays demonstrated that JNJ-8003 inhibited nucleotide polymerization at the early stages of RNA transcription and replication. Our results support that JNJ-8003 binding modulates a functional interplay between the capping and RdRp domains, and this molecular insight could accelerate the design of broad-spectrum antiviral drugs.

Abstract In complex social environments, individuals may interact with not only novel and familiar conspecifics but also kin and non-kin. The ability to distinguish between conspecific identities is crucial for most animals, yet how the brain processes conspecific type and how animals may alter behavior accordingly is not well known. We examined whether the communally breeding spiny mouse (Acomys cahirinus) responds differently to conspecifics that vary in novelty and kinship. In a group interaction test, we found that males can distinguish novel kin from novel non-kin, and preferentially spend time with novel kin over familiar kin and novel non-kin. To determine whether kinship and novelty status are differentially represented in the brain, we conducted immediate early gene tests, which revealed the dorsal, but not ventral, lateral septum differentially processes kinship. Neither region differentially processes social novelty. Further, males did not exhibit differences in prosocial behavior toward novel and familiar conspecifics but exhibited more prosocial behavior with novel kin than novel non-kin. These results suggest that communally breeding species may have evolved specialized neural circuitry to facilitate a bias to be more affiliative with kin, regardless of whether they are novel or familiar, potentially to promote prosocial behaviors, thereby facilitating group cohesion.

Abstract Background Delayed access to care may contribute to disparities in prostate cancer (PCa). The Affordable Care Act (ACA) aimed at increasing access and reducing healthcare disparities, but its impact on timely treatment initiation for PCa men is unknown. Methods Men with intermediate‐ and high‐risk PCa diagnosed 2010–2016 and treated with curative surgery or radiotherapy were identified in the National Cancer Database. Multivariable logistic regression modeled the effect of race and insurance type on treatment delay >180 days after diagnosis. Cochran–Armitage test measured annual trends in delays, and joinpoint regression assessed if 2014, the year the ACA became fully operationalized, was significant for inflection in crude rates of major delays. Results Of 422,506 eligible men, 18,720 (4.4%) experienced >180‐day delay in treatment initiation. Compared to White patients, Black (OR 1.79, 95% CI 1.72–1.87, p

Abstract Macrophages infected with Gram-negative bacteria expressing Type III secretion system (T3SS) activate the NLRC4 inflammasome, resulting in Gasdermin D (GSDMD)-dependent, but GSDME independent IL-1β secretion and pyroptosis. Here we examine inflammasome signaling in neutrophils infected with Pseudomonas aeruginosa strain PAO1 that expresses the T3SS effectors ExoS and ExoT. IL-1β secretion by neutrophils requires the T3SS needle and translocon proteins and GSDMD. In macrophages, PAO1 and mutants lacking ExoS and ExoT (ΔexoST) require NLRC4 for IL-1β secretion. While IL-1β release from ΔexoST infected neutrophils is also NLRC4-dependent, infection with PAO1 is instead NLRP3-dependent and driven by the ADP ribosyl transferase activity of ExoS. Genetic and pharmacologic approaches using MCC950 reveal that NLRP3 is also essential for bacterial killing and disease severity in a murine model of P. aeruginosa corneal infection (keratitis). Overall, these findings reveal a function for ExoS ADPRT in regulating inflammasome subtype usage in neutrophils versus macrophages and an unexpected role for NLRP3 in P. aeruginosa keratitis.

Tumor mutational burden (TMB) is a biomarker that predicts response to immune checkpoint inhibitor therapy. We currently lack a comprehensive understanding of how genomic and clinical factors correlate with TMB. We used a clinicogenomic database to assess independent predictors of TMB levels. The study included 2740 prostate cancer specimens from prostate gland (51.6%), lymph nodes (14.6%), and bone (10.4%). Androgen deprivation therapy use beyond 24 mo was weakly associated with high TMB (fold-change estimate [FCE] 1.14, 95% confidence interval [CI] 1.03–1.26; p = 0.009). In comparison to the prostate gland, metastases in the bladder (FCE 1.20, 95% CI 1.02–1.42; p = 0.029), liver (FCE 1.26, 95% CI 1.10–1.43; p

Abstract Background Most women with anovulatory infertility show polycystic ovarian syndrome (PCOS), and androgen excess is known as a key factor involved in pathogenicity of PCOS. However, the mechanism of follicular developmental arrest in PCOS is not completely understood. The reproductive function of Neuropeptide Y (NPY) in the ovary during folliculogenesis was previously reported; NPY function in apoptosis and proliferation of granulosa cells (GCs) is follicular-stage dependent. The objective of this study was to investigate the role of NPY in ovarian follicular development and the pathogenesis of PCOS. Methods To simulate the PCOS phenotype using a rat model, 21-day old Sprague Dawley rats were implanted with dihydrotestosterone (DHT) capsule (83 µg/day) and euthanized after 28 days. mRNA and protein content of NPY and its receptors were assessed in GCs from DHT treated rats using RT-qPCR and Western blot, respectively. Proliferation and apoptosis of GCs was assessed using Ki67- and TUNEL assays. Finally, NPY levels were measured in human follicular fluid (FF) from matched PCOS and non-PCOS patients using ELISA. Results GCs from DHT treated rats (PCOS-GCs) contained significantly less NPY protein and Npy mRNA by 0.16- and 0.56-fold, respectively, and more NPY receptor type 2 and 5 protein by 2.21- and 3.17-fold, respectively, when compared to sham control. Addition of recombinant NPY to PCOS-GCs culture did not alter Ki67-positive but significantly decreased TUNEL-positive cells by 0.65-fold, but not to baseline levels. There was no significant difference in NPY levels in FF between PCOS and non-PCOS subjects. Conclusions These results indicate that DHT modulates expression of NPY and its receptors, NPY decreases DHT-induced GCs apoptosis. That alterations in NPY’s function might be involved in follicular developmental failure of PCOS.

The Woven EndoBridge (WEB) (MicroVention/Terumo) device is a treatment option for wideneck bifurcation aneurysms. An uncommon adverse effect is WEB device migration. While certain bailout strategies for WEB recovery have been described, there is still a paucity of information on optimal strategies to maximize both short and long-term post-operative outcomes. We add 2 cases at our institution to the existing literature of WEBectomy in the setting of complicated intracranial aneurysm treatment. We discuss the long-term imaging outcomes with additional fluoroscopy video demonstrating our technique. Our findings reflect a clear benefit for the use of the Amplatz GooseneckTM microsnare (Medtronic) device as a means of WEB recovery, coupled with potential stent-assisted WEB embolization to remove the aneurysm from the parent circulation, while minimizing recurrence and thromboembolic complications.

Objective: The Identifying Depression Early in Adolescence Risk Score (IDEA-RS) was recently developed in Brazil using data from the Pelotas 1993 Birth Cohort to estimate the individualized probability of developing depression in adolescence. This model includes 11 sociodemographic variables and has been assessed in longitudinal studies from four other countries. We aimed to test the performance of IDEA-RS in an independent, community-based, school-attending sample within the same country: the Brazilian High-Risk Cohort. Methods: Standard external validation, refitted, and case mix-corrected models were used to predict depression among 1442 youth followed from a mean age of 13.5 years at baseline to 17.7 years at follow-up, using probabilities calculated with IDEA-RS coefficients. Results: The area under the curve was 0.65 for standard external validation, 0.70 for the case mix-corrected model, and 0.69 for the refitted model, with discrimination consistently above chance for predicting depression in the new dataset. There was some degree of miscalibration, corrected by model refitting (calibration-in-the-large reduced from 0.77 to 0). Conclusion: IDEA-RS was able to parse individuals with higher or lower probability of developing depression beyond chance in an independent Brazilian sample. Further steps should include model improvements and additional studies in populations with high levels of subclinical symptoms to improve clinical decision making.

El presente artículo científico busca recopilar los principales aportes del seminario final de graduación titulado: manifestaciones del bienestar desde las vivencias de hombres en adultez intermedia que experimentaron separación de pareja. El objetivo general es analizar estas manifestaciones propuestas desde el bienestar. Se utilizan antecedentes contextuales y empíricos nacionales e internacionales relacionados con el tema del bienestar y las relaciones de pareja, para contextualizar los hallazgos de la investigación. En cuanto a la disciplina de Orientación, se toman en cuenta los tres pilares fundamentales que caracterizan la disciplina: prevención, intervención social y desarrollo, resaltando que esta área puede brindar alternativas precisas que permitan el crecimiento integral de las personas con experiencias de la separación en esta etapa de la adultez intermedia. La investigación utiliza un enfoque cualitativo y una metodología fenomenológica, donde se hicieron entrevistas a profundidad a seis hombres en etapa de adultez intermedia. La aplicación de esta técnica de investigación contribuyó en el autoconocimiento y la comprensión de las experiencias de los hombres participantes mediante la recopilación de sus testimonios. Para el análisis de la información se utilizan tablas de consistencia, en la que se contrasta la bibliografía pertinente con las narraciones de los participantes. Se visualizan en los hallazgos, aspectos específicos para la promoción del bienestar integral desde la intervención orientadora. Esta puede brindar el apoyo colaborativo entre iguales, lo cual resulta muy valioso para afrontar el proceso de separación con distintas opciones en función del bienestar de cada hombre. Se recomienda la articulación de este tipo de procesos, en los que los hombres puedan explorar sus emociones en grupo y a partir de ello generar herramientas que aumenten sus niveles de bienestar.

BackgroundHIV, opioid use disorder (OUD), and mental health challenges share multiple syndemic risk factors. Each can be effectively treated with routine outpatient appointments, medication management, and psychosocial support, leading implementers to consider integrated screening and treatment for OUD and mental health in HIV care. Provider perspectives are crucial to understanding barriers and strategies for treatment integration.MethodsWe conducted in-depth qualitative interviews with 21 HIV treatment providers and social services providers (12 individual interviews and 1 group interview with 9 participants) to understand the current landscape, goals, and priorities for integrated OUD, mental health, and HIV care. Providers were purposively recruited from known clinics in Mecklenburg County, North Carolina, U.S.A. Data were analyzed using applied thematic analysis in the NVivo 12 software program and evaluated for inter-coder agreement.ResultsParticipants viewed substance use and mental health challenges as prominent barriers to engagement in HIV care. However, few organizations have integrated structured screening for substance use and mental health into their standard of care. Even fewer screen for opioid use. Although medication assisted treatment (MAT) is effective for mitigating OUD, providers struggle to connect patients with MAT due to limited referral options, social barriers such as housing and food insecurity, overburdened staff, stigma, and lack of provider training. Providers believed there would be clear benefit to integrating OUD and mental health treatment in HIV care but lacked resources for implementation.ConclusionsIntegration of screening and treatment for substance use and mental health in HIV care could mitigate many current barriers to treatment for all three conditions. Efforts are needed to train HIV providers to provide MAT, expand resources, and implement best practices.

Food insecurity impacts the lives of 7.6 million U.S. adults aged 60 and older and is linked to numerous life challenges. This study examined the nature of food insecurity among community-based participants ≥65 years in a north Florida county and conceptualized food insecurity as encompassing the lack of food and individual adaptability. Thus, food insecurity was measured using three dependent variables: (1) worrying that food would run out, (2) cutting meal size or skipping meals, and (3) food not lasting. Logistic regression revealed that older participants, those with better-perceived health status, and those who were confident that they could find solutions to their problems had lower odds of reporting food insecurity. However, respondents who lived in low-income, low-access zip codes and those who received food assistance were more likely to report food insecurity. To improve outcomes and reduce healthcare disparities, solutions to food insecurity must vary in focus and approach.

Social contact refers to the facilitation of connection and interactions between people with and without mental health conditions. It can be achieved, for example, through people sharing their lived experience of mental health conditions, which is an effective strategy for stigma reduction. Meaningful involvement of people with lived experience (PWLE) in leading and co-leading anti-stigma interventions can/may promote autonomy and resilience. Our paper aimed to explore how PWLE have been involved in research and anti-stigma interventions to improve effective means of involving PWLE in stigma reduction activities in LMICs. A qualitative collective case study design was adopted. Case studies from four LMICs (China, Ethiopia, India and Nepal) are summarized, briefly reflecting on the background of the work, alongside anticipated and experienced challenges, strategies to overcome these, and recommendations for future work. We found that the involvement of PWLEs in stigma reduction is commonly a new concept in LMIC. Experienced and anticipated challenges were similar, such as identifying suitable persons to engage in the work and sustaining their involvement. Such an approach can be difficult because PWLE might be apprehensive about the negative consequences of disclosure. In many case studies, we found that long-standing professional connectedness, continued encouragement, information sharing, debriefing and support helped the participants’ involvement. We recommend that confidentiality of the individual, cultural norms and family concerns be prioritized and respected during the implementation. Taking into account socio-cultural contextual factors, it is possible to directly involve PWLEs in social contact-based anti-stigma interventions.

Currently available pain assessment scales focus on pain-related symptoms and limitations imposed by pain. Validated assessment tools that measure how pain is regulated by those who live well with pain are missing. This study seeks to fill this gap by describing the development and preliminary validation of the Biobehavior Life Regulation (BLR) scale. The BLR scale assesses engagement, social relatedness, and self-growth in the presence of chronic pain and the unpredictability of chronic pain. Sources for items included survivor strategies, patient experiences, existing scales, and unpredictable pain research. Review for suitability yielded 52 items. Validation measures were identified for engagement, social relatedness, self-growth, and unpredictability of pain. The study sample (n = 202) represented patients treated in the Phoenix VA Health Care System (n = 112) and two community clinics (n = 90). Demographic characteristics included average age of 52.5, heterogeneous in ethnicity and race at the VA, mainly Non-Hispanic White at the community clinics, 14 years of education, and pain duration of 18 years for the VA and 15.4 years for community clinics. Exploratory factor analysis using Oblimin rotation in the VA sample (n = 112) yielded a two-factor solution that accounted for 48.23% of the total variance. Confirmatory factor analysis (CFA) in the same sample showed high correlations among items in Factor 1, indicating redundancy and the need to further reduce items. The final CFA indicated a 2-factor solution with adequate fit to the data. The 2-factor CFA was replicated in Sample 2 from the community clinics (n = 90) with similarly adequate fit to the data. Factor 1, Pain Regulation, covered 8 items of engagement, social relatedness, and self-growth while Factor 2, Pain Unpredictability, covered 6 items related to the experience of unpredictable pain. Construct validity showed moderate to higher Pearson correlations between BLR subscales and relevant well-established constructs that were consistent across VA and community samples. The BLR scale assesses adaptive regulation strategies in unpredictable pain as a potential tool for evaluating regulation resources and pain unpredictability.

People living with HIV (PLWH) experience unique stressors that contribute to emotional distress, and PLWH are more than twice as likely to die by suicide when compared to the general population. In countries like Tanzania, there is a relatively high burden of HIV but few resources to support mental health needs. To gain a better understanding of mental health challenges experienced by PLWH in northern Tanzania and identify opportunities for intervention, we interviewed 12 mental health professionals working in the Kilimanjaro region. Thematic analysis was used to explore drivers and impacts of emotional distress, community influences on mental health, and gaps and barriers to existing mental health care. Perspectives from mental health workers highlight the compounding effects of stress related to HIV status, family conflict, finances, and other social challenges, which can lead to poor HIV treatment outcomes and suicidal ideation. Cultural beliefs and stigma surrounding both mental health and HIV limit care-seeking behavior for mental health issues. Those who do seek care often encounter barriers related to poor mental health infrastructure, including a lack of providers, limited financial resources, and little integration into other health services. There is a clear need for investment in the mental health care system, as well as interventions to improve knowledge and perceptions of mental health and comprehensively address stressors. We describe feedback on a proposed telehealth counseling intervention integrated into routine HIV services, which shows strong potential to mitigate barriers to mental health treatment, reduce suicidal ideation, and support the wellbeing of PLWH.

Objective: Sympathetic innervation plays a pivotal role in regulating cardiovascular health, and its dysregulation is implicated in a wide spectrum of cardiovascular diseases. This study seeks to evaluate the impact of denervation of the abdominal aorta on its morphology and wall homeostasis. Methods: Male and female Sprague-Dawley rats (N = 12), aged 3 months, underwent midline laparotomy for infrarenal aorta exposure. Chemical denervation was induced via a one-time topical application of 10% phenol (n = 6), whereas sham controls received phosphate-buffered saline (n = 6). Animals were allowed to recover and subsequently were sacrificed after 6 months for analysis encompassing morphology, histology, and immunohistochemistry. Results: At 6 months post-treatment, abdominal aortas subjected to phenol denervation still exhibited a significant reduction in nerve fiber density compared with sham controls. Denervated aortas demonstrated reduced intima-media thickness, increased elastin fragmentation, decreased expression of vascular smooth muscle proteins (α-SMA and MYH11), and elevated adventitial vascular density. Sex-stratified analyses revealed additional dimorphic responses, particularly in aortic collagen and medial cellular density in female animals. Conclusions: Single-timepoint phenol-based chemical denervation induces alterations in abdominal aortic morphology and vascular remodeling over a 6-month period. These findings underscore the potential of the sympathetic nervous system as a therapeutic target for aortic pathologies. Clinical Relevance: Aortic remodeling remains an important consideration in the pathogenesis of aortic disease, including occlusive, aneurysmal, and dissection disease states. The paucity of medical therapies for the treatment of aortic disease has driven considerable interest in elucidating the pathogenesis of these conditions; new therapeutic targets are critically needed. Here, we show significant remodeling after phenol-induced denervation with morphologic, histologic, and immunohistochemical features. Future investigations should integrate sympathetic dysfunction as a potential driver of pathologic aortic wall changes with additional consideration of the sympathetic nervous system as a therapeutic target.