" I carry their stories home ": experiences of nurses and midwives caring for perinatal adolescent mothers in primary health care settings in Rwanda.

INTRODUCTION: Adolescent mothers require trauma- and violence-informed care during the perinatal period due to trauma histories and ongoing violence as a result of pregnancy. Nurses and midwives play a critical role in caring for adolescent mothers in primary healthcare settings in Rwanda in the perinatal period. PURPOSE: To explore the experiences of nurses and midwives working with adolescent mothers in selected primary healthcare settings in Rwanda to inform the delivery of trauma- and violence- informed care. METHODS: This study utilized an interpretive description qualitative approach and was conducted in eight primary healthcare settings in Rwanda. Twelve nurses and midwives working in perinatal services and four heads of health centers participated in in-depth individual interviews. Data were analyzed thematically. RESULTS: The analysis revealed four main themes and 11 (sub-themes): (a) relational practice (being creative and flexible, "lending them our ears"); (b) individual challenges of providing care to adolescent mothers (lack of knowledge to provide care related to gender-based violence, and gendered experience); (c) factors contributing to workarounds (inflexible guidelines, lack of protocol and procedures, lack of nurses' and midwives' in service training, and the physical structure of the perinatal environment); and (d) vicarious trauma (living the feelings, "I carry their stories home," and hypervigilance in parenting). CONCLUSION: Nurses and midwives find caring for adolescent mothers challenging due to their unique needs. These needs require them to be creative, adaptable, and attentive listeners to better understand their challenges. These practitioners face difficulties such as insufficient specific knowledge related to, for example, gender-based violence, inflexible guidelines, and a lack of protocols and training. Additionally, in the perinatal environment attention to the needs of practitioners in those settings is often lacking, and many nurses and midwives report experiencing vicarious trauma. Consequently, there is a pressing need for guidelines and protocols specifically tailored for the care of adolescent mothers. Ongoing trauma- and violence- informed care training and professional education should be provided to enhance the ability of nurses and midwives to care for adolescent mothers and prevent re-traumatization and mitigate vicarious trauma effectively.

Exploring perinatal ketamine for postpartum depression following cesarean section: A systematic review.

The aim of this study was to explore the use of perinatal ketamine to see if it can be used for the reduction of postpartum depression (PPD) following cesarean section (C-section). PubMed, Cochrane, and Web of Science were the primary databases used for this review. Search terms used on January 5, 2024 incorporated "ketamine," "C-section," "postpartum depression," and related synonyms. The criteria for inclusion centered on studies published between January 1, 2008 and January 5, 2024. The final selection of articles was screened based on extraction criteria leaving eight randomized control trials in the final review. The selected data from the studies incorporated sample characteristics, study and population characteristics, and quantitative analyses covering Edinburgh Postpartum Depression Scale (EPDS) scores and depression rates. The Risk of Bias assessment was utilized to gain a deeper understanding of the quality of methodology used by the research studies. The review showed that ketamine can reduce the symptoms of PPD in mothers who have recently undergone C-sections. Some studies showed decreased EPDS scores following the administration of ketamine while two studies also reported no significant differences in PPD following ketamine administration in C-section patients. For example, Ma et al. found that the EPDS score at postpartum day 4 was significantly lower in the ketamine group compared with the control group (p = 0.007) while Yang et al. found that there were no significant differences between the ketamine and control group at 3 days postpartum (p = 0.553). The research from this review suggests that ketamine administration can prevent or decrease the symptoms of PPD, but more research is needed to establish the causal relationship between ketamine dosage and PPD in C-section patients.

A Deep Learning Approach for the Identification of the Molecular Subtypes of Pancreatic Ductal Adenocarcinoma Based on Whole-Slide Pathology Images.

Delayed diagnosis and treatment resistance make pancreatic ductal adenocarcinoma (PDAC) mortality rates high. Identifying molecular subtypes can improve treatment, but current methods are costly and time-consuming. In this study, deep learning models were utilized to identify histological features that classify PDAC molecular subtypes based on routine hematoxylin-eosin (H&E)-stained histopathological slides. 97 histopathology slides associated with resectable PDAC from the Cancer Genome Atlas (TCGA) project were utilized to train a deep learning model and tested the performance on 44 needle biopsy material (110 slides) from a local annotated patient cohort. The model achieved balanced accuracy of 96.19% and 83.03% in identifying the classical and basal subtypes of PDAC in the TCGA and the local cohort, respectively. This study provides a promising method to cost-effectively and rapidly classifying PDAC molecular subtypes based on routine H&E slides, potentially leading to more effective clinical management of this disease.

Enhancing Drug Discovery and Development through the Integration of Medicinal Chemistry, Chemical Biology, and Academia-Industry Partnerships: Insights from Roche's Endocannabinoid System Projects.

The endocannabinoid system (ECS) is a critical regulatory network composed of endogenous cannabinoids (eCBs), their synthesizing and degrading enzymes, and associated receptors. It is integral to maintaining homeostasis and orchestrating key functions within the central nervous and immune systems. Given its therapeutic significance, we have launched a series of drug discovery endeavors aimed at ECS targets, including peroxisome proliferator-activated receptors (PPARs), cannabinoid receptors types 1 (CB1R) and 2 (CB2R), and monoacylglycerol lipase (MAGL), addressing a wide array of medical needs. The pursuit of new therapeutic agents has been enhanced by the creation of specialized labeled chemical probes, which aid in target localization, mechanistic studies, assay development, and the establishment of biomarkers for target engagement. By fusing medicinal chemistry with chemical biology in a comprehensive, translational end-to-end drug discovery strategy, we have expedited the development of novel therapeutics. Additionally, this strategy promises to foster highly productive partnerships between industry and academia, as will be illustrated through various examples.

Enhanced Corrosion Protection of Printed Circuit Board Electronics using Cold Atmospheric Plasma-Assisted SiOx Coatings.

The miniaturization and widespread deployment of electronic devices across diverse environments have heightened their vulnerability to corrosion, particularly affecting copper traces within printed circuit boards (PCBs). Conventional protective methods, such as conformal coatings, face challenges including the necessity for a critical thickness to ensure effective barrier properties and the requirement for multiple steps of drying and curing to eliminate solvent entrapment within polymer coatings. This study investigates cold atmospheric plasma (CAP) as an innovative technique for directly depositing ultrathin silicon oxide (SiOx) coatings onto copper surfaces to enhance corrosion protection in PCBs. A systematic investigation was undertaken to examine how the scanning speed of the CAP deposition head impacts the film quality and corrosion resistance. The research aims to determine the optimal scanning speed of the CAP deposition head that achieves complete surface coverage while promoting effective cross-linking and minimizing unreacted precursor entrapment, resulting in superior electrical barrier and mechanical properties. The CAP coating process demonstrated the capability of depositing SiOx onto copper surfaces at various thicknesses ranging from 70 to 1110 nm through a single deposition process by simply adjusting the scanning speed of the plasma head (5-75 mm/s). Evaluation of material corrosion barrier characteristics revealed that scanning speeds of 45 mm/s of the plasma deposition head provided an effective coating thickness of 140 nm, exhibiting superior corrosion resistance (30-fold) compared to that of uncoated copper. As a proof of concept, the efficacy of CAP-deposited SiOx coatings was demonstrated by protecting an LED circuit in saltwater and by coating printed circuits for potential agricultural sensor applications. These CAP-deposited coatings offer performance comparable to or superior to traditional conformal polymeric coatings. This research presents CAP-deposited SiOx coatings as a promising approach for effective and scalable corrosion protection in miniaturized electronics.

Locus coeruleus microstructural integrity is associated with vigilance vulnerability to sleep deprivation.

Insufficient sleep compromises cognitive performance, diminishes vigilance, and disrupts daily functioning in hundreds of millions of people worldwide. Despite extensive research revealing significant variability in vigilance vulnerability to sleep deprivation, the underlying mechanisms of these individual differences remain elusive. Locus coeruleus (LC) plays a crucial role in the regulation of sleep-wake cycles and has emerged as a potential marker for vigilance vulnerability to sleep deprivation. In this study, we investigate whether LC microstructural integrity, assessed by fractional anisotropy (FA) through diffusion tensor imaging (DTI) at baseline before sleep deprivation, can predict impaired psychomotor vigilance test (PVT) performance during sleep deprivation in a cohort of 60 healthy individuals subjected to a rigorously controlled in-laboratory sleep study. The findings indicate that individuals with high LC FA experience less vigilance impairment from sleep deprivation compared with those with low LC FA. LC FA accounts for 10.8% of the variance in sleep-deprived PVT lapses. Importantly, the relationship between LC FA and impaired PVT performance during sleep deprivation is anatomically specific, suggesting that LC microstructural integrity may serve as a biomarker for vigilance vulnerability to sleep loss.

Morning resting hypothalamus-dorsal striatum connectivity predicts individual differences in diurnal sleepiness accumulation.

While the significance of obtaining restful sleep at night and maintaining daytime alertness is well recognized for human performance and overall well-being, substantial variations exist in the development of sleepiness during diurnal waking periods. Despite the established roles of the hypothalamus and striatum in sleep-wake regulation, the specific contributions of this neural circuit in regulating individual sleep homeostasis remain elusive. This study utilized resting-state functional magnetic resonance imaging (fMRI) and mathematical modeling to investigate the role of hypothalamus-striatum connectivity in subjective sleepiness variation in a cohort of 71 healthy adults under strictly controlled in-laboratory conditions. Mathematical modeling results revealed remarkable individual differences in subjective sleepiness accumulation patterns measured by the Karolinska Sleepiness Scale (KSS). Brain imaging data demonstrated that morning hypothalamic connectivity to the dorsal striatum significantly predicts the individual accumulation of subjective sleepiness from morning to evening, while no such correlation was observed for the hypothalamus-ventral striatum connectivity. These findings underscore the distinct roles of hypothalamic connectivity to the dorsal and ventral striatum in individual sleep homeostasis, suggesting that hypothalamus-dorsal striatum circuit may be a promising target for interventions mitigating excessive sleepiness and promoting alertness.

Endothelial extracellular vesicles enhance vascular self-assembly in engineered human cardiac tissues.

The fabrication of complex and stable vasculature in engineered cardiac tissues represents a significant hurdle towards building physiologically relevant models of the heart. Here, we implemented a 3D model of cardiac vasculogenesis, incorporating endothelial cells (EC), stromal cells, and human iPSC-derived cardiomyocytes (CM) in a fibrin hydrogel. The presence of CMs disrupted vessel formation in 3D tissues, resulting in the upregulation of endothelial activation markers and altered extracellular vesicle (EV) signaling in engineered tissues as determined by the proteomic analysis of culture supernatant. miRNA sequencing of CM- and EC-secreted EVs highlighted key EV-miRNAs that were postulated to play differing roles in cardiac vasculogenesis, including the let-7 family and miR-126-3p in EC-EVs. In the absence of CMs, the supplementation of CM-EVs to EC monolayers attenuated EC migration and proliferation and resulted in shorter and more discontinuous self-assembling vessels when applied to 3D vascular tissues. In contrast, supplementation of EC-EVs to the tissue culture media of 3D vascularized cardiac tissues mitigated some of the deleterious effects of CMs on vascular self-assembly, enhancing the average length and continuity of vessel tubes that formed in the presence of CMs. Direct transfection validated the effects of the key EC-EV miRNAs let-7b-5p and miR-126-3p in improving the maintenance of continuous vascular networks. EC-EV supplementation to biofabricated cardiac tissues and microfluidic devices resulted in tissue vascularization, illustrating the use of this approach in the engineering of enhanced, perfusable, microfluidic models of the myocardium.

The relationship between momentary experiential avoidance and anxiety symptoms.

BACKGROUND: Experiential avoidance (EA) may serve as a risk factor for a wide range of anxiety-related psychopathology. Anxiety is thought to trigger the use of EA, while also serving as a consequence of EA efforts. Previous ecological momentary assessment (EMA) studies found that EA was associated with greater anxiety in nonclinical undergraduates and patients with social anxiety disorder. METHODS: The present study examined the in-the-moment, bidirectional relationship between EA, perceived stress, and two facets of anxiety (autonomic arousal and worry/misery) in a sample of treatment-seeking patients broadly diagnosed with an anxiety-related disorder (N = 46). Participants completed a baseline assessment followed by an EMA assessment period (assessments three times daily for seven days). We hypothesized that there would be a bidirectional relationship between EA and anxiety/stress. RESULTS: Results largely supported a unidirectional relationship such that greater EA at one time point predicted higher stress at a later time point controlling for previous stress levels and linear time. Trend-level associations between EA and anxiety symptoms are discussed. CONCLUSIONS: The current study provides important insight into the relationship between EA and anxiety symptoms in a clinical sample of participants with anxiety-related disorders.

Heterologous Expression of Epoxomicin in Escherichia coli.

Epoxomicin is an epoxyketone proteasome inhibitor with synthetic derivatives approved or under investigation for treatment of multiple myeloma. To leverage the advantages of Escherichia coli as a rapidly growing and readily engineered host for the production of epoxomicin and analogues, we expressed codon-optimized versions of the epoxomicin biosynthetic genes, epxD, epxE, and epxF. Epoxomicin was detected, but the major product was a ketone resulting from α,ß-keto acid precursor decarboxylation. Epoxomicin yield was improved by altering the copy numbers of each gene and creating a fusion of epxE and epxF. Our optimized system offers promise for efficient engineering and biosynthesis of improved epoxomicin analogues.

An evaluation form to aid dairy producers to systematically assess cows prior to culling.

Objective: The objective of this prospective observational research project was to have dairy producers use and assess the utility of a cull cow evaluation form. Animals: Cull dairy cows. Procedure: Veterinarians were recruited to enrol a purposively selected group of dairy producers into a project to evaluate a cull cow evaluation form. Producers were provided with evaluation forms and asked to complete a form for every cow they culled from their herd from January to June 2017, inclusive. Results: A total of 44 producers used the form to record information on 323 cows prior to transport. Conclusion and clinical relevance: Despite the completion of 323 forms, only ~1/3 were completed fully, with compliance highest for body condition score, lameness, and temperature recordings (> 90% of forms). A cull cow evaluation form may improve the thoroughness and consistency of dairy producer assessment of cull dairy cows for fitness for transport.

Un formulaire d'évaluation pour aider les producteurs laitiers à évaluer systématiquement les vaches avant la réforme. Objectif: L'objectif de ce projet de recherche observationnelle prospective était d'amener les producteurs laitiers à utiliser et à évaluer l'utilité d'un formulaire d'évaluation des vaches de réforme. Animaux: Vaches laitières réformées. Procédure: Des vétérinaires ont été recrutés pour inscrire un groupe de producteurs laitiers sélectionnés à dessein dans un projet visant à évaluer un formulaire d'évaluation des vaches réformées. Les producteurs ont reçu des formulaires d'évaluation et ont été invités à remplir un formulaire pour chaque vache qu'ils ont éliminée de leur troupeau de janvier à juin 2017 inclusivement. Résultats: Au total, 44 producteurs ont utilisé le formulaire pour enregistrer des informations sur 323 vaches avant le transport. Conclusion et pertinence clinique: Malgré la complétion de 323 formulaires, seulement environ 1/3 ont été entièrement remplis, avec une conformité plus élevée pour le score d'état corporel, les boiteries et les enregistrements de température (> 90 % des formulaires). Un formulaire d'évaluation des vaches laitières réformées peut améliorer la rigueur et la cohérence de l'évaluation par le producteur laitier des vaches laitières réformées quant à leur aptitude au transport.(Traduit par Dr Serge Messier).

Rationally reprogramming single-cell aging trajectories and lifespan through dynamic modulation of environmental inputs.

How do variations in nutrient levels influence cellular lifespan? A dynamical systems model of a core circuit involved in yeast aging suggests principles underlying lifespan extension observed at static and alternating glucose levels that are reminiscent of intermittent fasting regimens.

Opioid use disorder risk alleles in self-reported assigned African American/Afro-Caribbean and European biogeographical genetic ancestry groups and in males and females.

The influence of genetic variants related to opioid use disorder (OUD) was evaluated using multiple logistic regression analysis in self-reported assigned African American/Afro-Caribbean and European biogeographical ancestry groups (BGAGs) and by sex. From a sample size of 1301 adult patients (>18 years of age) seen in emergency departments of three medical centers in Ohio, six variants were found to be associated with OUD. Two of the variants, rs2740574 (CYP3A4) and rs324029 (DRD3), were included in the analysis having met criteria of at least five subjects for each BGAG, variant carrier status, and OUD status combinations. Variant carriers in the African/Afro-Caribbean BGAG had slightly lower predicted probabilities of OUD. Variant carriers in the European BGAG had slightly higher predicted probabilities of OUD. Relative to sex, all the six variants met evaluation criteria (five subjects for all sex, variant, and OUD status combinations). No statistically significant interactions were found between a given variant, BGAGs and sex. Findings suggest variant testing relative to OUD risk can be applied across BGAGs and sex, however, studies in larger populations are needed.

Converging deep learning and human-observed tumor-adipocyte interaction as a biomarker in colorectal cancer.

BACKGROUND: Tumor-Adipose-Feature (TAF) as well as SARIFA (Stroma AReactive Invasion Front Areas) are two histologic features/biomarkers linking tumor-associated adipocytes to poor outcomes in colorectal cancer (CRC) patients. Whereas TAF was identified by deep learning (DL) algorithms, SARIFA was established as a human-observed histopathologic biomarker. METHODS: To study the overlap between TAF and SARIFA, we performed a systematic pathological review of TAF based on all published image tiles. Additionally, we analyzed the presence/absence of TAF in SARIFA-negative CRC cases to elucidate the biologic and prognostic role of a direct tumor-adipocyte contact. TCGA-CRC gene expression data is investigated to assess the association of FABP4 (fatty-acid binding protein 4) and CD36 (fatty-acid translocase) with both TAF and CRC prognosis. RESULTS: By investigating the TAF/SARIFA overlap, we show that many TAF patches correspond to the recently described SARIFA-phenomenon. Even though there is a pronounced morphological and biological overlap, there are differences in the concepts. The presence of TAF in SARIFA-negative CRCs is not associated with poor outcomes in this cohort, potentially highlighting the importance of a direct tumor-adipocyte interaction. Upregulation of FABP4 and CD36 gene expression seem both linked to a poor prognosis in CRC. CONCLUSIONS: By proving the substantial overlap between human-observed SARIFA and DL-based TAF as morphologic biomarkers, we demonstrate that linking DL-based image features to independently developed histopathologic biomarkers is a promising tool in the identification of clinically and biologically meaningful biomarkers. Adipocyte-tumor-cell interactions seem to be crucial in CRC, which should be considered as biomarkers for further investigations.

Different methods exist in assessing samples removed from cancer patients during surgery. We linked two independently established tissue-based methods for determining the outcome of colorectal cancer patients together: tumor adipose feature (TAF) and Stroma AReactive Invasion Front Areas (SARIFA). SARIFA as biological feature was observed solely by humans and TAF was identified by the help of a computer algorithm. We examined TAF in many cancer slides and looked at whether they showed similarities to SARIFA. TAF often matched SARIFA, but not always. Interestingly, these methods could be used to predict outcomes for patients and are associated with specific gene expression involved in tumor and fat cell interaction. Our study shows that combining computer algorithms with human expertize in evaluating tissue samples can identify meaningful features in patient samples, which may help to predict the best treatment options.

Genotyped RHD+ red cells for D-positive patients with sickle cell disease with conventional RHD and unexpected anti-D.

Anti-D can occur in D-positive patients who inherit RHD genetic variants encoding partial D antigen expression, but unexpected anti-D is also found in the plasma of patients with sickle cell disease who have conventional RHD gene(s) and are transfused with units from Black donors. These anti-D are likely stimulated by variant Rh expressed on donor cells, however patients with anti-D, regardless of cause, are transfused for a lifetime with D-negative (Rh-negative) blood. This results in significant increased use of Rh-negative units, especially for those requiring chronic transfusion, which can strain Rh-negative blood inventories. We tested whether D-positive patients who made anti-D and had conventional RhD by RHD genotyping could safely be returned to D-positive transfusions without anti-D reappearance or compromised RBC survival using RHD genotype-matched units from Black donors. Five patients receiving chronic red cell exchange received an increasing number of D-positive units per procedure with a total of 72 D-positive RHD genotyped units transfused, with no anti-D restimulation. Unexpected anti-C and anti-E were identified during the study associated with donors with variant RHCE alleles. RH genotyping of D-positive units for transfusion may improve use and allocation of valuable Black donor units and reduce demand for Rh-negative blood.

The Association Between the Development of Cam Morphology During Skeletal Growth in High-Impact Athletes and the Presence of Cartilage Loss and Labral Damage in Adulthood: A Prospective Cohort Study With a 12-Year Follow-up.

BACKGROUND: Cam morphology develops during skeletal growth, but its influence on cartilage and the labrum in high-impact athletes later in life is unknown. PURPOSE: To (1) explore the association between the presence and duration of cam morphology during adolescence and the cartilage and labral status 7 to 12 years later and (2) report the prevalence of cartilage loss and labral damage in a population of young male athletes (<32 years old) who played professional soccer during skeletal growth. STUDY DESIGN: Cohort study (Prognosis); Level of evidence, 2. METHODS: A total of 89 healthy male academy soccer players from the Dutch soccer club Feyenoord (aged 12-19 years) were included at baseline. At baseline and 2.5- and 5-year follow-ups, standardized supine anteroposterior pelvis and frog-leg lateral radiographs of each hip were obtained. At 12-year follow-up, magnetic resonance imaging of both hips was performed. Cam morphology was defined by a validated alpha angle ≥60° on radiographs at baseline or 2.5- or 5-year follow-up when the growth plates were closed. Hips with the presence of cam morphology at baseline or at 2.5-year follow-up were classified as having a "longer duration" of cam morphology. Hips with cam morphology only present since 5-year follow-up were classified as having a "shorter duration" of cam morphology. At 12-year follow-up, cartilage loss and labral abnormalities were assessed semiquantitatively. Associations were estimated using logistic regression, adjusted for age and body mass index. RESULTS: Overall, 35 patients (70 hips) with a mean age of 28.0 ± 2.0 years and mean body mass index of 24.1 ± 1.8 participated at 12-year follow-up. Cam morphology was present in 56 of 70 hips (80%). The prevalence of cartilage loss was 52% in hips with cam morphology and 21% in hips without cam morphology (adjusted odds ratio, 4.52 [95% CI, 1.16-17.61]; P = .03). A labral abnormality was present in 77% of hips with cam morphology and in 64% of hips without cam morphology (adjusted odds ratio, 1.99 [95% CI, 0.59-6.73]; P = .27). The duration of cam morphology did not influence these associations. CONCLUSION: The development of cam morphology during skeletal growth was associated with future magnetic resonance imaging findings consistent with cartilage loss in young adults but not with labral abnormalities.

Standing-up against moral violations: The predicting role of attribution, kinship, and severity.

Witnesses of moral violations stand up for their moral principles, despite facing substantial costs for intervening. Notwithstanding its importance, little is known whether responsibility attributions and the relation between the victim and a witness (i.e., kinship) have different effects on the intention to intervene in situations of different severity (e.g., moral courage situations). We predict an interaction between the situation's severity and the victims' responsibility for their plight. In less-severe situations, witnesses would be less willing to help when they perceive the victim to be responsible for their plight. However, those who are not seen as responsible would receive more help. For more-severe situations, responsibility is predicted to have no effect. Opposite effects are predicted for the relationship between the helper and the victim. We further predict that perceived costs for helping mediates witnesses' willingness to intervene. Two studies showed that people are more willing to help individuals who are perceived as being innocent, but only in less-severe situations. In more-severe situations, people's willingness to intervene increases, regardless of responsibility attributions. We did not observe effects for kinship. Moreover, we provide partial evidence that witnesses of more-severe situations indeed accept higher costs for intervention.