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El objetivo del presente trabajo fue evaluar en una muestra de gays y lesbianas, las emociones que experimentaron en su primera relación sexual, así como la relación con el uso de condón, planeación, concenso y edad del debut sexual. Participaron 336 hombres y mujeres, quienes respondieron en línea el cuestionario de Emociones, Estrés y Afrontamiento y algunas preguntas adicionales sobre su primera relación sexual. Se encontraron diferencias significativas en las emociones que experimentan hombres y mujeres, y entre aquellos que usaron condón, planearon y consensuaron su primera relación sexual. Los resultados se discuten en términos de cómo las emociones pueden afectar la vida sexual de gays y lesbianas.

Abstract Background The identification of circulating biomarkers that closely correlate with Parkinson’s Disease (PD) has failed several times in the past. Nevertheless, in this pilot study, a translational approach was conducted, allowing the evaluation of the plasma levels of two mitochondrial-related proteins, whose combination leads to a robust model with potential diagnostic value to discriminate the PD patients from matched controls. Methods The proposed translational approach was initiated by the analysis of secretomes from cells cultured under control or well-defined oxidative stress conditions, followed by the identification of proteins related to PD pathologic mechanisms that were altered between the two states. This pipeline was further translated into the analysis of undepleted plasma samples from 28 control and 31 PD patients. Results From the secretome analysis, several mitochondria-related proteins were found to be differentially released between control and stress conditions and to be able to distinguish the two secretomes. Similarly, two mitochondrial-related proteins were found to be significantly changed in a PD cohort compared to matched controls. Moreover, a linear discriminant model with potential diagnostic value to discriminate PD patients was obtained using the combination of these two proteins. Both proteins are associated with apoptotic mitochondrial changes, which may correspond to potential indicators of cell death. Moreover, one of these proteins, the VPS35 protein, was reported in plasma for the first time, and its quantification was only possible due to its previous identification in the secretome analysis. Conclusions In this work, an adaptation of a translational pipeline for biomarker selection was presented and transposed to neurological diseases, in the present case Parkinson’s Disease. The novelty and success of this pilot study may arise from the combination of: i) a translational research pipeline, where plasma samples are interrogated using knowledge previously obtained from the evaluation of cells’ secretome under oxidative stress; ii) the combined used of statistical analysis and an informed selection of candidates based on their link with relevant disease mechanisms, and iii) the use of SWATH-MS, an untargeted MS method that allows a complete record of the analyzed samples and a targeted data extraction of the quantitative values of proteins previously identified.

The pinewood nematode (PWN), Bursaphelenchus xylophilus, one of the most serious forest pests worldwide, is considered the causal agent of the pine wilt disease (PWD). The main host species belong to the genus Pinus, and a variation in the susceptibility of several pine species to PWN infection is well-known. It is also recognized that there is variation in the virulence among B. xylophilus isolates. In the present study, we applied a quantitative mass spectrometry-based proteomics approach to perform a deep characterization of proteomic changes across two B. xylophilus isolates with different virulence from different hosts and geographical origins. A total of 1,456 proteins were quantified and compared in the two isolates secretomes, and a total of 2,741 proteins were quantified and compared in the nematode proteomes in pine tree extract and fungus stimuli conditions. From the proteomic analyses, a group of proteins was selected and identified as potential virulence biomarkers and shed light on putative most pathogenic proteins of this plant-parasitic nematode. Proteomic data are available via ProteomeXchange with identifier PXD029377.

Machine learning methods for health care delivery optimization have the potential to improve retention in HIV care, a critical target of global efforts to end the epidemic. However, these methods have not been widely applied to medical record data in low- and middle-income countries. We used an ensemble decision tree approach to predict risk of disengagement from HIV care (missing an appointment by ≥28 days) in Tanzania. Our approach used routine electronic medical records (EMR) from the time of antiretroviral therapy (ART) initiation through 24 months of follow-up for 178 adults (63% female). We compared prediction accuracy when using EMR-based predictors alone and in combination with sociodemographic survey data collected by a research study. Models that included only EMR-based indicators and incorporated changes across past clinical visits achieved a mean accuracy of 75.2% for predicting risk of disengagement in the next 6 months, with a mean sensitivity of 54.7% for targeting the 30% highest-risk individuals. Additionally including survey-based predictors only modestly improved model performance. The most important variables for prediction were time-varying EMR indicators including changes in treatment status, body weight, and WHO clinical stage. Machine learning methods applied to existing EMR data in resource-constrained settings can predict individuals' future risk of disengagement from HIV care, potentially enabling better targeting and efficiency of interventions to promote retention in care.

Adolescents experience significant barriers, including stigma and discrimination, to accessing voluntary family planning and reproductive health (FP/RH) services in Rwanda. Self-care interventions have been shown to reduce social barriers to FP/RH care, but little is known about the effectiveness of digital self-care for adolescents, particularly in low-resource settings. This paper presents findings from a pilot study of CyberRwanda, a digital self-care intervention providing comprehensive sexuality education and confidential online ordering of contraceptives for school-aged youth in Rwanda through a rights-based approach. A mixed-methods pilot study was conducted from November 2019 to February 2020 to assess feasibility, acceptability, and engagement and to inform a future impact evaluation. Surveys were administered to a random sample of 158 students aged 12–19 years in three secondary schools. In-depth interviews were conducted with students, parents, teachers, pharmacists, district-level administrators, and youth centre staff. Descriptive statistics were calculated and qualitative data were analyzed using a thematic coding approach. One hundred and fifty-eight surveys and 28 interviews were conducted. Results revealed high demand for CyberRwanda in schools. Students were interested in engaging with the program and found the FP/RH content relevant to their needs. However, few purchased contraceptive products through the online ordering system. There are preliminary indications that CyberRwanda may improve access to FP/RH information. An extended implementation period and further research are needed to measure the long-term impacts of the program and evaluate whether this digital self-care intervention can increase uptake of contraceptive methods and reduce adolescent pregnancy among school-aged youth.

OBJECTIVES/GOALS: Accumulating evidence supports the involvement of immune and inflammatory pathways in Bipolar Disorder (BD) pathophysiology. This pilot study aims to determine if altered peripheral IL-2, TNF-a, IL-4, IL-6, IL-10, IFN-y, IL-17A levels are associated with BD across mood episodes (euthymic, manic, depressive), and worsen neurocognitive function. METHODS/STUDY POPULATION: Twenty-eight participants (17 cases and 11 controls) were recruited. We assessed the clinical features and cytokine plasma levels of participants. Cytokines were measured using Flow Cytometry. All subjects were interviewed by a trained psychiatrist. Each participant was fasting before the blood sample was taken. Neuropsychological tests were used to measure verbal fluency, speed processing, working memory/attention, visuospatial skills, verbal learning, executive functions, and motor skills. Descriptive statistics were used to calculate the demographic characteristics of the sample. An independent-sample Kruskal-Wallis Test and Mann-Whitney Test were carried out using SPSS version 21. RESULTS/ANTICIPATED RESULTS: Serum biomarker concentration showed a decrease in levels of IL-4 (anti-inflammatory) in BD patients vs healthy controls (p < .05). There was a major concentration of IL-6 (pro-inflammatory) on bipolar patients vs controls (p = .003). When we analyze the results with the mood episodes, we found that patients with bipolar depression showed decreased levels of IL-4 (p = .046) and increase levels of IL-6 (p = .020) in comparison to the manic or euthymic episodes. In the neurocognitive tests, we found that the control participants had better performance in the working memory domain (p = .038) and also in the general performance (p = .036) in comparison to bipolar patients. We found also a positive significant correlation between IL-4 and verbal learning in the control sample (.829, p = .003). DISCUSSION/SIGNIFICANCE: The findings evidence a significant immune activation in bipolar patients, in particular during the depressive episode. Participants with BD have a decrease in the protective levels of IL-4 combined with high levels of IL-6 when compared to healthy controls. Worse neurocognitive functioning was found in bipolar patients.

The new era of immune-oncology has brought complexities and challenges that emphasize the need to identify new strategies and models to develop successful and cost-effective therapies. The inclusion of a canine model in the drug development of cancer immunotherapies is being widely recognized as a valid solution to overcome several hurdles associated with conventional preclinical models. Driven by the success of immunotherapies in the treatment of human non-Hodgkin lymphoma (NHL) and by the remarkable similarities of canine NHL to its human counterpart, canine NHL has been one of the main focus of comparative research. Under the present review, we summarize a general overview of the challenges and prospects of today's cancer immunotherapies and the role that comparative medicine might play in solving the limitations brought by this rapidly expanding field. The state of art of both human and canine NHL and the rationale behind the use of the canine model to bridge the translational gap between murine preclinical studies and human clinical trials are addressed. Finally, a review of currently available immunotherapies for canine NHL is described, highlighting the potential of these therapeutic options.

Abstract Background Rapid (“warm”) autopsies of patients with advanced metastatic cancer provide important insight into the natural history, pathobiology and histomorphology of disease in treatment-resistant tumors. Plasmacytoid urothelial carcinoma (PUC) is a rare variant of urothelial carcinoma characterized by neoplastic cells morphologically resembling plasma cells. PUC is typically aggressive, high-stage at presentation, and associated with poor outcomes. Recurrence is common in PUC, with the majority of recurrences occurring in the peritoneum. Case presentation Here, we report rapid autopsy findings from a patient with recurrent PUC. The patient had persistent pain after cystoprostatectomy, although initial post-operative imaging showed no evidence of disease. Imaging obtained shortly before his death showed only subtle growth along vascular tissue planes; however, extensive disease was seen on autopsy. Plasmacytoid tumor cells formed sheets involving many serosal surfaces. Molecular interrogation confirmed a mutation in CDH1 exon 12 leading to early truncation of the CDH1 protein in the tumor cells. Conclusions The sheet-like growth pattern of PUC makes early phases of disease spread much more difficult to capture on cross-sectional imaging. Alternative forms of surveillance may be required for detection of recurrent PUC, and providers may need to treat based on symptoms and clinical suspicion.

Heart health: understanding pacemaker cells The heart’s pacemaker cells contain mitochondria that are smaller than average and require less energy than other heart cells, properties that help make them naturally resilient to stress. Cardiac pacemaker cells constitute a tiny proportion of the heart’s cells, yet play a critical role in maintaining a steady heartbeat. However, quite how pacemaker cells maintain their automatic rhythm is unclear because their scarcity makes them difficult to study. To examine the cells’ metabolic state further, Hee Cheol Cho at Emory University, Atlanta, and Brian Foster at Johns Hopkins University School of Medicine, Baltimore, and co-workers therefore induced pacemaker cells by adding an embryonic protein to heart muscle cells. The induced pacemaker cells survived well under oxidative stress. The team identified a protein in the pacemakers’ mitochondrial membranes, the expression of which directly influences rhythm responses.

Abstract Background Malaria is one of the most prevalent tropical infectious diseases. Since recently cases of artemisinin resistance were reported, novel anti-malarial drugs are required which differ from artemisinins in structure and biological target. The plasmodial glycogen synthase kinase-3 (PfGSK-3) was suggested as a new anti-malarial drug target. 4-Phenylthieno[2,3-b]pyridines were previously identified as selective PfGSK-3 inhibitors with antiplasmodial activity. The present study aims at identifying a molecular position on this scaffold for the attachment of side chains in order to improve solubility and antiplasmodial activity. Furthermore, the role of axial chirality in the compound class for antiplasmodial activity and PfGSK-3 inhibition was investigated. Methods 4-Phenylthieno[2,3-b]pyridines with substituents in 4-position of the phenyl ring were docked into the ATP binding site of PfGSK-3. The compounds were synthesized employing a Thorpe reaction as final step. The enantiomers of one congener were separated by chiral HPLC. All derivatives were tested for inhibition of asexual erythrocytic stages of transgenic NF54-luc Plasmodium falciparum. Selected compounds with promising antiplasmodial activity were further evaluated for inhibition of HEK293 cells as well as inhibition of isolated PfGSK-3 and HsGSK-3. The kinetic aqueous solubility was assessed by laser nephelometry. Results The para position at the 4-phenyl ring of the title compounds was identified as a suitable point for the attachment of side chains. While alkoxy substituents in this position led to decreased antiplasmodial activity, alkylamino groups retained antiparasitic potency. The most promising of these congeners (4h) was investigated in detail. This compound is a selective PfGSK-3 inhibitor (versus the human GSK-3 orthologue), and exhibits improved antiplasmodial activity in vitro as well as better solubility in aqueous media than its unsubstituted parent structure. The derivative 4b was separated into the atropisomers, and it was shown that the (+)-enantiomer acts as eutomer. Conclusions The attachment of alkylamino side chains leads to the improvement of antiplasmodial activity and aqueous solubility of selective PfGSK-inhibitors belonging to the class of 4-phenylthieno[2,3-b]pyridines. These molecules show axial chirality, a feature of high impact for biological activity. The findings can be exploited for the development of improved selective PfGSK-3 inhibitors.

The Oglán Alto Protective Forest has an area of 3100 hectares and is dominated by Amazonian lowland and piedmont forests, which harbor great diversity of fauna and flora. However, such diversity has been poorly studied, especially insects. Here we present an inventory of the dung beetles (Coleoptera: Scarabaeidae: Scarabaeinae) for this locality. A total of 10,627 individuals, belonging to 17 genera and 65 species, were determined during 18 months of collection, in which 11 different sampling methods were used. This research presents and updated checklist and a photographic guide of the main genera and species of dung beetles identified in the study area.

We conducted a cluster-randomized hybrid effectiveness-implementation study of CyberRwanda, a digital family planning and reproductive health intervention for Rwandan adolescents. Sixty schools were randomized 1:1:1 to control or to one of two implementation models-self-service (self-guided access on tablets) or facilitated (peer-led clubs plus tablet access) with no masking. Eligible participants were aged 12-19 years, in secondary school levels 1 or 2, and willing to provide consent or assent/parental consent and contact information for follow-up. In 2021, 6,078 randomly selected adolescents were enrolled. At 24 months, 91.3% of participants were retained and included in the primary intention-to-treat analyses (control, n = 1,845; self-service, n = 1,849 and facilitated, n = 1,858). There were no adverse events related to the study. CyberRwanda did not affect the primary outcomes of modern contraceptive use (prevalence ratio (PR) = 1.04; 95% confidence interval (CI) = 0.76, 1.42), childbearing (PR = 1.33; 95% CI = 0.71, 2.50) and HIV testing (PR = 1.00; 95% CI = 0.91, 1.11) in the full sample. Significantly higher modern contraceptive use observed in the CyberRwanda facilitated arm in a prespecified analysis of sexually active participants suggests that longer-term evaluation is needed to examine effects as more of the study population becomes sexually active and has increased demand for contraception. ClinicalTrials.gov registration: NCT04198272 .

BackgroundSmall incentives could improve engagement in HIV care. We evaluated the short-term and longer-term effects of financial incentives for visit attendance on viral suppression among adults initiating antiretroviral therapy (ART) in Tanzania.MethodsIn a type 1 hybrid effectiveness-implementation study, we randomised (1:1) 32 primary care HIV clinics in four Tanzanian regions to usual care (control group) or the intervention (usual care plus ≤6 monthly incentives [22 500 Tanzanian Shillings, about US$10, each], conditional on visit attendance). Adults (aged ≥18 years) initiating ART (

IntroductionAdverse sexual and reproductive health (SRH) outcomes, such as unplanned pregnancies and HIV infection, disproportionately affect adolescent girls and young women (AGYW; aged 15-24 years) in east Africa. Increasing uptake of preventive SRH services via innovative, youth-centred interventions is imperative to addressing disparities in SRH outcomes.Methods and analysisFrom 2018 to 2019, we used human-centred design to co-develop a theoretically driven HIV and pregnancy prevention intervention for AGYW at private drug shops called Accredited Drug Dispensing Outlets (ADDOs) in Tanzania. The result, Malkia Klabu (Queen Club), was a customer loyalty programme designed to strengthen ADDOs' role as SRH providers while encouraging uptake of critical SRH prevention products among AGYW. Malkia Klabu members had access to free contraceptives and oral HIV self-test (HIVST) kits and earned punches on a loyalty card for other shop purchases; punches were redeemable for small prizes. Our pilot among 40 shops showed that intervention ADDOs had higher AGYW patronage and distributed more HIVST kits and contraceptives to AGYW relative to business-as-usual (ie, client purchasing) comparison shops. We will conduct a cluster-randomised controlled trial (c-RCT) among 120-140 ADDOs in 40 health catchment areas in Shinyanga and Mwanza Regions (Lake Zone), Tanzania. ADDO shop recruitment includes a 1-month run-in with a tablet-based electronic inventory management system for tracking shop transactions, followed by enrolment, randomisation and a 24-month trial period. Our c-RCT evaluating the human-centred design-derived intervention will assess population impact on the primary outcomes of HIV diagnoses and antenatal care registrations, measured with routine health facility data. We will also assess secondary outcomes focusing on mechanisms of action, evaluate programme exposure and AGYW behaviour change in interviews with AGYW, and assess shop-level implementation strategies and fidelity.Ethics and disseminationEthical approval was granted from both the University of California, San Francisco and the Tanzanian National Institute for Medical Research. Study progress and final outcomes will be posted annually to the National Clinical Trials website; study dissemination will occur at conferences, peer-reviewed manuscripts and local convenings of stakeholders.Trial registration numberNCT05357144.

This chapter centers on our reflections and pedagogical moves as two bilingual educators at a Hispanic-Serving Institution on the borderland region of South Texas, a predominantly bilingual and bicultural community. Specifically, the chapter documents how we embrace a translanguaging pedagogical stance. Translanguaging practices are identity markers and represent the complex ways bilinguals use their linguistic repertoire to communicate across contexts and to negotiate social identities (García & Li Wei, 2014; Martinez-Roldán, 2015). Drawing on García, Johnson, and Seltzer’s (2017) conceptualization of a translanguaging “corriente,” we describe our translanguaging stance and moves as we, respectively, design and teach two undergraduate courses: an upper-level undergraduate Foundations of Bilingual Education course and an undergraduate Rhetoric and Composition I course. We identify tensions, as well as commonalities and differences in our experience enacting translanguaging pedagogies and assignments in two different disciplinary areas. We also present two students’ reflections and assignments to illustrate the outcomes of our translanguaging pedagogies.

Resumo As Parcerias Público-Privadas (PPP) são arranjos institucionais que envolvem atores públicos e privados numa relação contratual de longa duração. Assumindo-se como contratos incompletos, propendem para o aumento dos custos de transação e estão associadas aos problemas típicos das relações de principal-agente. Neste contexto, a academia tem dedicado atenção ao estudo dos fatores críticos para o bom desempenho das PPP, entre os quais, os fatores de natureza política e institucional, a que dedicamos o artigo. Por meio de uma metodologia qualitativa, assente na realização de entrevistas em profundidade e numa criteriosa análise documental, o artigo propõe-se estudar o caso das PPP de infraestruturas rodoviárias em Portugal, com falhas já identificadas e atualmente sob forte escrutínio público.

The pinewood nematode (PWN), Bursaphelenchus xylophilus, the pine wilt disease’s (PWD) causal agent, is a migratory endoparasitic nematode skilled to feed on pine tissues and on fungi that colonize the trees. In order to study B. xylophilus secretomes under the stimulus of pine species with different susceptibilities to disease, nematodes were exposed to aqueous pine extracts from Pinus pinaster (high-susceptible host) and P. pinea (low-susceptible host). Sequential windowed acquisition of all theoretical mass spectra (SWATH-MS) was used to determine relative changes in protein amounts between B. xylophilus secretions, and a total of 776 secreted proteins were quantified in both secretomes. From these, 22 proteins were found increased in the B. xylophilus secretome under the P. pinaster stimulus and 501 proteins increased under the P. pinea stimulus. Functional analyses of the 22 proteins found increased in the P. pinaster stimulus showed that proteins with peptidase, hydrolase, and antioxidant activities were the most represented. On the other hand, gene ontology (GO) enrichment analysis of the 501 proteins increased under the P. pinea stimulus revealed an enrichment of proteins with binding activity. The differences detected in the secretomes highlighted the diverse responses from the nematode to overcome host defenses with different susceptibilities and provide new clues on the mechanism behind the pathogenicity of this plant-parasitic nematode. Proteomic data are available via ProteomeXchange with identifier PXD024011.

Objectives: Guideline recommendations for patients with either a high or a low risk of obstructive coronary artery disease (CAD) are clear. However, the evidence for initial risk stratification in patients with an intermediate risk of CAD is still unclear, despite the availability of multiple non-invasive assessment strategies. The aim of this study was to synthesize the evidence for this population to provide more informed recommendations.Background: A meta-analysis was performed to systematically assess the diagnostic accuracy of vasodilator myocardial perfusion cardiovascular magnetic resonance imaging (pCMR) and dobutamine stress echocardiography (DSE) for the detection of relevant CAD. In contrast to previous work, this meta-analysis follows rigorous selection criteria in regards to the risk stratification and a narrowly prespecified definition of their invasive reference tests, resulting in unprecedentedly informative results for this reference group.Data Collection and Analysis: From the 5,634 studies identified, 1,306 relevant articles were selected after title screening and further abstract screening left 865 studies for full-text review. Of these, 47 studies fulfilled all inclusion criteria resulting in a total sample size of 4,742 patients.Results: pCMR studies showed a superior sensitivity [0.88 (95% confidence interval (CI): 0.85–0.90) vs. 0.72 (95% CI: 0.61–0.81)], diagnostic odds ratio (DOR) [38 (95% CI: 29–49) vs. 20 (95% CI: 9–46)] and an augmented post-test probability [negative likelihood ratio (LR) of 0.14 (95% CI: 0.12–0.18) vs. 0.31 (95% CI: 0.21, 0.46)] as compared to DSE. Specificity was statistically indifferent [0.84 (95% CI: 0.81–0.87) vs. 0.89 (95% CI: 0.83–0.93)].Conclusion: The results of this systematic review and meta-analysis suggest that pCMR has a superior diagnostic test accuracy for relevant CAD compared to DSE. In patients with intermediate risk of CAD only pCMR can reliably rule out relevant stenosis. In this risk cohort, pCMR can be offered for initial risk stratification and guidance of further invasive treatment as it also rules in relevant CAD.

Hypertension is the most determinant risk factor for cardiovascular diseases. Early intervention and future therapies targeting hypertension mechanisms may improve the quality of life and clinical outcomes. Hypertension has a complex multifactorial aetiology and was recently associated with protein homeostasis (proteostasis). This work aimed to characterize proteostasis in easy-to-access plasma samples from 40 individuals, 20 with controlled hypertension and 20 age- and gender-matched normotensive individuals. Proteostasis was evaluated by quantifying the levels of protein aggregates through different techniques, including fluorescent probes, slot blot immunoassays and Fourier-transform infrared spectroscopy (FTIR). No significant between-group differences were observed in the absolute levels of various protein aggregates (Proteostat or Thioflavin T-stained aggregates; prefibrillar oligomers and fibrils) or total levels of proteostasis-related proteins (Ubiquitin and Clusterin). However, significant positive associations between Endothelin 1 and protein aggregation or proteostasis biomarkers (such as fibrils and ubiquitin) were only observed in the hypertension group. The same is true for the association between the proteins involved in quality control and protein aggregates. These results suggest that proteostasis mechanisms are actively engaged in hypertension as a coping mechanism to counteract its pathological effects in proteome stability, even when individuals are chronically medicated and presenting controlled blood pressure levels.

The vast ocean holds many unexplored organisms with unique adaptive features that enable them to thrive in their environment. The secretion of fluorescent proteins is one of them, with reports on the presence of such compounds in marine annelids being scarce. The intertidal Eulalia sp. is an example. The worm secretes copious amounts of mucus, that when purified and concentrated extracts, yield strong fluorescence under UV light. Emission has two main maxima, at 400 nm and at 500 nm, with the latter responsible for the blue–greenish fluorescence. Combining proteomics and transcriptomics techniques, we identified ubiquitin, peroxiredoxin, and 14-3-3 protein as key elements in the mucus. Fluorescence was found to be mainly modulated by redox status and pH, being consistently upheld in extracts prepared in Tris-HCl buffer with reducing agent at pH 7 and excited at 330 nm. One of the proteins associated with the fluorescent signal was localized in secretory cells in the pharynx. The results indicate that the secretion of fluorescent proteinaceous complexes can be an important defense against UV for this dweller. Additionally, the internalization of fluorescent complexes by ovarian cancer cells and modulation of fluorescence of redox status bears important considerations for biotechnological application of mucus components as markers.

Mitochondrial deregulation has gained increasing support as a pathological mechanism in Huntington’s disease (HD), a genetic-based neurodegenerative disorder caused by CAG expansion in the HTT gene. In this study, we thoroughly investigated mitochondrial-based mechanisms in HD patient-derived iPSC (HD-iPSC) and differentiated neural stem cells (NSC) versus control cells, as well as in cells subjected to CRISPR/Cas9-CAG repeat deletion. We analyzed mitochondrial morphology, function and biogenesis, linked to exosomal release of mitochondrial components, glycolytic flux, ATP generation and cellular redox status. Mitochondria in HD cells exhibited round shape and fragmented morphology. Functionally, HD-iPSC and HD-NSC displayed lower mitochondrial respiration, exosomal release of cytochrome c, decreased ATP/ADP, reduced PGC-1α and complex III subunit expression and activity, and were highly dependent on glycolysis, supported by pyruvate dehydrogenase (PDH) inactivation. HD-iPSC and HD-NSC mitochondria showed ATP synthase reversal and increased calcium retention. Enhanced mitochondrial reactive oxygen species (ROS) were also observed in HD-iPSC and HD-NSC, along with decreased UCP2 mRNA levels. CRISPR/Cas9-CAG repeat deletion in HD-iPSC and derived HD-NSC ameliorated mitochondrial phenotypes. Data attests for intricate metabolic and mitochondrial dysfunction linked to transcriptional deregulation as early events in HD pathogenesis, which are alleviated following CAG deletion.

Background: Heavy load carrying has been associated with musculoskeletal discomfort (MSD) and disability. However, there is a lack of research investigating this association in resource-constrained settings where heavy load carrying by women is common. Objective(s): We assessed the impact of heavy load carrying on musculoskeletal pain and disability among women in Shinyanga Region, Tanzania, in an exploratory cross-sectional study. Methods: Eligible participants were a convenience sample of women, at least 18 years of age, who passed a study recruitment site carrying a load. We collected information on load-carrying practices, including frequency and time spent carrying water, wood, agricultural products, coal, sand, or rocks, and measured the weight of the load carried at the time. Outcomes included self-reported MSDs, defined as experiencing pain lasting >3 days in the neck, head, back, knees, feet and/or ankles within the last 1 year, and related disability. Using multivariable logistic regression we assessed for associations between load carrying exposures and MSDs and disability. Findings: Results showed a high prevalence of MSDs across the body regions assessed and evidence to suggest a relationship of back pain and related disability with several measures of load-carrying, including duration, frequency, and weight. Multivariable analyses revealed associations of increased load carrying exposures with low back pain (LBP) and related disability, including statistically significant increases in odds of LBP with increasing weight, total duration of load carrying/week and cumulative loads/week. Conclusions: Findings indicate a substantial burden of MSDs and disability in this population of women who carry heavy loads daily. The extent of discomfort and disability increased with increasing exposure to various load-carrying measures, especially for LBP. Larger epidemiologic studies that definitively assess relationships of load carrying with MSDs and disability are warranted.

Abstract Background The postpartum period is an opportune time for contraception adoption, as women have extended interaction with the reproductive healthcare system and therefore more opportunity to learn about and adopt contraceptive methods. This may be especially true for women who experience unintended pregnancy, a key target population for contraceptive programs and programs to eliminate mother-to-child HIV transmission. Among women in Zimbabwe surveyed in 2014, we examined the relationship between pregnancy intention associated with a woman’s most recent pregnancy, and her subsequent postpartum contraceptive use. Methods In our analysis we utilized a dataset from a random selection of catchment areas in Zimbabwe to examine the association between pregnancy intention of most recent pregnancy and subsequent postpartum contraceptive use using multinomial logistic regression models. We also explored whether this association differed by women’s HIV status. Finally, we examined the association between pregnancy intention and changes in contraception from the pre- to postpartum periods. Results Findings suggest that women who reported that their pregnancy was unintended adopted less modern (all non-traditional) contraceptive methods overall, but adopted long-acting reversible contraception (LARC) more frequently than women reporting an intended pregnancy (OR 1.41; CI 1.18, 1.68). Among HIV-positive women, this relationship was particularly strong (OR 3.12; CI 1.96, 4.97). However, when examining changes in contraceptive use from the pre-pregnancy to the postpartum period, women who had an unintended pregnancy had lower odds of changing to a more effective method postpartum overall (OR 0.71; CI 0.64, 0.79). Conclusions We did not find evidence of higher modern method adoption in the postpartum period among women with an unintended pregnancy. However, women who were already on a method in the pre-pregnancy period were catalyzed to move to more effective methods (such as LARC) postpartum. This study provides evidence of low modern (non-traditional) method adoption in general in the postpartum period among a vulnerable sub-population in Zimbabwe (women who experience unintended pregnancy). Simultaneously, however, it shows a relatively greater portion specifically of LARC use among women with an unintended pregnancy. Further research is needed to more closely examine the motivations behind these contraceptive decisions in order to better inform distribution and counseling programs.

Background Wearable fitness trackers are increasingly used in healthcare applications; however, the frequent updating of these devices is at odds with traditional medical device practices.Objective Our objective was to explore the nature and frequency of wearable tracker updates recorded in device changelogs, to reveal the chronology of updates and to estimate the intervals where algorithm updates could impact device validations.Method Updates for devices meeting selection criteria (that included their use in clinical trials) were independently labelled by four researchers according to simple function and specificity schema.Results Device manufacturers have diverse approaches to update reporting and changelog practice. Visual representations of device changelogs reveal the nature and chronology of device iterations. 13% of update items were unspecified and 32% possibly affected validations with as few as 5 days between updates that may affect validation.Conclusion Manufacturers could aid researchers and health professionals by providing more informative device update changelogs.

Despite use of 7-valent pneumococcal conjugate vaccine, incidence of pleural effusion and empyema (pediatric complicated pneumococcal pneumonia [PCPP]) is reportedly increasing globally. We cultured and performed PCR on 152 pleural fluid samples recovered from pediatric patients in Portugal during 2010–2015 to identify and serotype Streptococcus pneumoniae. We identified only 17 cases by culture, but molecular methods identified S. pneumoniae in 68% (92/135) of culture-negative samples. The most frequent serotypes were 3, 1, and 19A, together accounting for 62% (68/109) of cases. Nineteen cases attributable to 13-valent pneumococcal conjugate vaccine (PCV13) serotypes (mostly serotype 3) were detected among 22 children age-appropriately vaccinated with PCV13. The dominance of the additional serotypes included in PCV13 among PCPP cases in Portugal continues, even with PCV13 available on the private market (without reimbursement) since 2010 and with average annual coverage of 61% among age-eligible children. Our data suggest reduced effectiveness of PCV13 against serotype 3 PCPP.

Abstract Background Current normalization methods for RNA-sequencing data allow either for intersample comparison to identify differentially expressed (DE) genes or for intrasample comparison for the discovery and validation of gene signatures. Most studies on optimization of normalization methods typically use simulated data to validate methodologies. We describe a new method, GeTMM, which allows for both inter- and intrasample analyses with the same normalized data set. We used actual (i.e. not simulated) RNA-seq data from 263 colon cancers (no biological replicates) and used the same read count data to compare GeTMM with the most commonly used normalization methods (i.e. TMM (used by edgeR), RLE (used by DESeq2) and TPM) with respect to distributions, effect of RNA quality, subtype-classification, recurrence score, recall of DE genes and correlation to RT-qPCR data. Results We observed a clear benefit for GeTMM and TPM with regard to intrasample comparison while GeTMM performed similar to TMM and RLE normalized data in intersample comparisons. Regarding DE genes, recall was found comparable among the normalization methods, while GeTMM showed the lowest number of false-positive DE genes. Remarkably, we observed limited detrimental effects in samples with low RNA quality. Conclusions We show that GeTMM outperforms established methods with regard to intrasample comparison while performing equivalent with regard to intersample normalization using the same normalized data. These combined properties enhance the general usefulness of RNA-seq but also the comparability to the many array-based gene expression data in the public domain.

The genus Serratia is widely distributed in soil, water, plants, animals, invertebrates, and humans. Some species of this genus have antifungal, antibacterial, and nematicidal activity. In this work, the nematicidal activity of the endophytic strain of Serratia sp. in chili, Capsicum annuum L., is reported, where at a bacterial concentration of 4 × 109 cel/mL, the penetration of nematodes into the roots significantly decreased by 91 and 55% at 7 and 21 days after inoculation. This bacterial concentration also significantly decreased the number of galls, eggs, egg masses and reproduction factor produced by Nacobbus aberrans in Chili plants, with respect to the control where this bacterial strain was not applied. In the analysis of the genome of the strain, based on average nucleotide identity (ANI), the isolate could be affiliated to the species Serratia ureilytica. The size of the genome is 5.4 Mb, with a 59.3% content of GC. Genes related to the synthesis of chitinases, siderophores, proteases C, serralisins, hemolysin, and serrawettin W2 that have been reported for biocontrol of nematodes were identified in the genome. It is the first report of Serratia ureilytica with nematicidal activity. Based on these results of nematicidal activity, this strain can be evaluated in the field as an alternative in the biocontrol of Nacobbus aberrans in chili cultivation.

Abstract Background Glioblastoma (GBM) is a highly aggressive primary brain cancer, for which curative therapies are not available. An emerging therapeutic approach suggested to have potential to target malignant gliomas has been based on the use of multipotent mesenchymal stem cells (MSCs), either unmodified or engineered to deliver anticancer therapeutic agents, as these cells present an intrinsic capacity to migrate towards malignant tumors. Nevertheless, it is still controversial whether this innate tropism of MSCs towards the tumor area is associated with cancer promotion or suppression. Considering that one of the major mechanisms by which MSCs interact with and modulate tumor cells is via secreted factors, we studied how the secretome of MSCs modulates critical hallmark features of GBM cells. Methods The effect of conditioned media (CM) from human umbilical cord perivascular cells (HUCPVCs, a MSC population present in the Wharton’s jelly of the umbilical cord) on GBM cell viability, migration, proliferation and sensitivity to temozolomide treatment of U251 and SNB-19 GBM cells was evaluated. The in vivo chicken chorioallantoic membrane (CAM) assay was used to evaluate the effect of HUCPVCs CM on tumor growth and angiogenesis. The secretome of HUCPVCs was characterized by proteomic analyses. Results We found that both tested GBM cell lines exposed to HUCPVCs CM presented significantly higher cellular viability, proliferation and migration. In contrast, resistance of GBM cells to temozolomide chemotherapy was not significantly affected by HUCPVCs CM. In the in vivo CAM assay, CM from HUCPVCs promoted U251 and SNB-19 tumor cells growth. Proteomic analysis to characterize the secretome of HUCPVCs identified several proteins involved in promotion of cell survival, proliferation and migration, revealing novel putative molecular mediators for the effects observed in GBM cells exposed to HUCPVCs CM. Conclusions These findings provide novel insights to better understand the interplay between GBM cells and MSCs, raising awareness to potential safety issues regarding the use of MSCs as stem-cell based therapies for GBM.

Abstract Background Glioblastoma (GBM), the most malignant primary brain tumor, leads to poor and unpredictable clinical outcomes. Recent studies showed the tumor microenvironment has a critical role in regulating tumor growth by establishing a complex network of interactions with tumor cells. In this context, we investigated how GBM cells modulate resident glial cells, particularly their paracrine activity, and how this modulation can influence back on the malignant phenotype of GBM cells. Methods Conditioned media (CM) of primary mouse glial cultures unexposed (unprimed) or exposed (primed) to the secretome of GL261 GBM cells were analyzed by proteomic analysis. Additionally, these CM were used in GBM cells to evaluate their impact in glioma cell viability, migration capacity and activation of tumor-related intracellular pathways. Results The proteomic analysis revealed that the pre-exposure of glial cells to CM from GBM cells led to the upregulation of several proteins related to inflammatory response, cell adhesion and extracellular structure organization within the secretome of primed glial cells. At the functional levels, CM derived from unprimed glial cells favored an increase in GBM cell migration capacity, while CM from primed glial cells promoted cells viability. These effects on GBM cells were accompanied by activation of particular intracellular cancer-related pathways, mainly the MAPK/ERK pathway, which is a known regulator of cell proliferation. Conclusions Together, our results suggest that glial cells can impact on the pathophysiology of GBM tumors, and that the secretome of GBM cells is able to modulate the secretome of neighboring glial cells, in a way that regulates the “go-or-grow” phenotypic switch of GBM cells.

In Colombia, labor inclusion is an issue that has been dealt with in different spaces of social interest. By 2011, according to the World Report on Disability, there were more than 1,000 million people with some disability and it is to be assumed that access to work is reduced due to this situation. MinSalud (2017) According to figures from DANE in Colombia, 6.4% of citizens have some type of disability, 52% of working age and only 15% of them work. (CONFANDI, 2015). Teleworking as a work modality allows us to comply with two schemes: stable employment hiring and labor inclusion of people with disabilities. In addition to avoiding their displacement, working from home is an ideal option for the disabled worker since most have physical spaces in their home adapted to their needs; and for the contracting companies since it alleviates the requirements of adaptation in their facilities in the circulation areas and in the sanitary services, among others. Thus, a high use of this style of work by workers with disabilities would be expected, however in this study carried out the percentage of disabled people is similar to that described in conventional work, so it would be worthwhile to encourage more teleworking among companies and in the disabled population. (Uribe S, 2017)

This Data in Brief contains results from three different survey logistic regression models comparing risks of self-reported diagnoses of cardiovascular and pulmonary diseases among smokers of menthol and non-menthol cigarettes. Analyses employ data from National Health and Nutrition Examination Survey (NHANES) cycles administered between 1999 and 2012, combined and in subsets. Raw data may be downloaded from the National Center for Health Statistics. Results were not much affected by which covariates were included in the models, but depended strongly on the NHANES cycles included in the analysis. All three models returned elevated risk estimates for three endpoints when they were run in individual NHANES cycles (congestive heart failure in 2001–02; hypertension in 2003–04; and chronic obstructive pulmonary disease in 2005–06), and all three models returned null results for these endpoints when data from 1999–2012 were combined.

El presente trabajo tuvo como objetivo identificar y evaluar la capacidad de degradación de microorganismos aislados de nódulos de mimosas, que puedan ser utilizados en procesos de biorremediación de suelos contaminados con fenantreno . Método . Se realizó el aislamiento de 122 cepas bacterianas de nódulos de mimosas; fueron crecidas en el medio de cultivo Maconkey para descartar enterobacterias. L as cepas bacterianas que dieron resultado negativo a esta prueba, fueron inoculadas en el medio de cultivo que contenía como úni ca fuente de carbono fenantreno; tres aislados tuvieron la capacidad de crecer en este medio. Las tres cepas fueron identificadas por secuencia del gen 1 6s ribosomal, se evaluó su capacidad de crecimiento en presencia de fenantreno mediante curvas de crecimiento microbiano; la capacidad para degradar fenantreno de las tres cepas fue cuantificada por cromatografía de gases acoplado a masas. Resultados . La s secuencias obtenidas del gen 16s ribosomal tienen relación genética con las especies de Burkholderia phenoliruptrix , Burkholderia phymatum y Rhizobium paknamense. El crecimiento microbiano de las tres cepas, suministradas con fenantreno, tuvieron un comp ortamiento similar al control , el cual contenía succinato como fuente de carbono. La cepa de Burkholderia sp. BB26 degradó 78.5 % , Burkholderia sp. BB24 68.5 % y Rhizobium sp. BY8 99%. Discusión . Los resultados de degradación de fenantreno por las cepas de Burkholderia sp. BB26 , Burkholderia sp. BB24 y Rhizobium sp. BY8 sugieren que las tres cepas tienen p otencial para utilizarse en procesos de biorremediación de suelos contaminados con fenantreno.

Abstract Every heartbeat originates from a tiny tissue in the heart called the sinoatrial node (SAN). The SAN harbors only ≈10 000 cardiac pacemaker cells, initiating an electrical impulse that captures the entire heart, consisting of billions of cardiomyocytes for each cardiac contraction. How these rare cardiac pacemaker cells (the electrical source) can overcome the electrically hyperpolarizing and quiescent myocardium (the electrical sink) is incompletely understood. Due to the scarcity of native pacemaker cells, this concept of source–sink mismatch cannot be tested directly with live cardiac tissue constructs. By exploiting TBX18 induced pacemaker cells by somatic gene transfer, 3D cardiac pacemaker spheroids can be tissue‐engineered. The TBX18 induced pacemakers (sphTBX18) pace autonomously and drive the contraction of neighboring myocardium in vitro. TBX18 spheroids demonstrate the need for reduced electrical coupling and physical separation from the neighboring ventricular myocytes, successfully recapitulating a key design principle of the native SAN. β‐Adrenergic stimulation as well as electrical uncoupling significantly increase sphTBX18s' ability to pace‐and‐drive the neighboring myocardium. This model represents the first platform to test design principles of the SAN for mechanistic understanding and to better engineer biological pacemakers for therapeutic translation.

Parkinson's disease (PD) is characterized by a selective loss of dopamine (DA) neurons in the human midbrain causing motor dysfunctions. The exact mechanism behind dopaminergic cell death is still not completely understood and, so far, no cure or neuroprotective treatment for PD is available. Recent studies have brought attention to the variety of bioactive molecules produced by mesenchymal stem cells (MSCs), generally referred to as the secretome. Herein, we evaluated whether human MSCs-bone marrow derived (hBMSCs) secretome would be beneficial in a PD pre-clinical model, when compared directly with cell transplantation of hBMSCs alone. We used a 6-hydroxydpomanie (6-OHDA) rat PD model, and motor behavior was evaluated at different time points after treatments (1, 4, and 7 weeks). The impact of the treatments in the recovery of DA neurons was estimated by determining TH-positive neuronal densities in the substantia nigra and fibers in the striatum, respectively, at the end of the behavioral characterization. Furthermore, we determined the effect of the hBMSCs secretome on the neuronal survival of human neural progenitors in vitro, and characterized the secretome through proteomic-based approaches. This work demonstrates that the injection of hBMSCs secretome led to the rescue of DA neurons, when compared to transplantation of hBMSCs themselves, which can explain the recovery of secretome-injected animals' behavioral performance in the staircase test. Moreover, we observed that hBMSCs secretome induces higher levels of in vitro neuronal differentiation. Finally, the proteomic analysis revealed that hBMSCs secrete important exosome-related molecules, such as those related with the ubiquitin-proteasome and histone systems. Overall, this work provided important insights on the potential use of hBMSCs secretome as a therapeutic tool for PD, and further confirms the importance of the secreted molecules rather than the transplantation of hBMSCs for the observed positive effects. These could be likely through normalization of defective processes in PD, namely proteostasis or altered gene transcription, which lately can lead to neuroprotective effects.

Maria Tavares's first monograph poses an immediate question: Are nonconforming women dispossessed from a country, any country? The provocative title sets in motion a study based on the comparative analysis of three female authors from Lusophone Africa, namely Dina Salústio from Cape Verde, Paulina Chiziane from Mozambique, and the Angolan Rosária da Silva. Tavares takes as her point of departure the fact that, despite their differences, all three were the first female writers to publish in the context of their respective independent nations.

Cells translate extracellular signals to regulate processes such as differentiation, metabolism and proliferation, via transmembranar receptors. G protein-coupled receptors (GPCRs) belong to the largest family of transmembrane receptors, with over 800 members in the human species. Given the variety of key physiological functions regulated by GPCRs, these are main targets of existing drugs. During normal aging, alterations in the expression and activity of GPCRs have been observed. The central nervous system (CNS) is particularly affected by these alterations, which results in decreased brain functions, impaired neuroregeneration, and increased vulnerability to neuropathologies, such as Alzheimer’s and Parkinson diseases. GPCRs signal via heterotrimeric G proteins, such as Go, the most abundant heterotrimeric G protein in CNS. We here review age-induced effects of GPCR signaling via the Gi/o subfamily at the CNS. During the aging process, a reduction in protein density is observed for almost half of the Gi/o-coupled GPCRs, particularly in age-vulnerable regions such as the frontal cortex, hippocampus, substantia nigra and striatum. Gi/o levels also tend to decrease with aging, particularly in regions such as the frontal cortex. Alterations in the expression and activity of GPCRs and coupled G proteins result from altered proteostasis, peroxidation of membranar lipids and age-associated neuronal degeneration and death, and have impact on aging hallmarks and age-related neuropathologies. Further, due to oligomerization of GPCRs at the membrane and their cooperative signaling, down-regulation of a specific Gi/o-coupled GPCR may affect signaling and drug targeting of other types/subtypes of GPCRs with which it dimerizes. Gi/o-coupled GPCRs receptorsomes are thus the focus of more effective therapeutic drugs aiming to prevent or revert the decline in brain functions and increased risk of neuropathologies at advanced ages.

Most of the redox proteomics strategies are focused on the identification and relative quantification of cysteine oxidation without considering the variation in the total levels of the proteins. However, protein synthesis and protein degradation also belong to the regulatory mechanisms of the cells, being therefore important to consider the changes in total protein levels in PTMs-focused analyses, such as cysteine redox characterization. Therefore, a novel integrative approach combining the SWATH-MS method with differential alkylation using a combination of commonly available alkylating reagents (oxSWATH) is presented, by which it is possible to integrate the information regarding relative cysteine oxidation with the analysis of the total protein levels in a cost-effective high-throughput approach.The proposed method was tested using a redox-regulated protein and further applied to a comparative analysis of secretomes obtained from cells cultured under control or oxidative stress conditions to strengthen the importance of considering the overall proteome changes. Using the OxSWATH method it was possible to determine both the relative proportion of reduced and reversible oxidized oxoforms, as well as the total levels of each oxoform by taking into consideration the total levels of the protein. Therefore, using OxSWATH the comparative analyses can be performed at two different levels by considering the relative proportion or the total levels at both peptide and protein level. Moreover, since samples are acquired in SWATH-MS mode, besides the redox centered analysis, a generic differential protein expression analysis can also be performed, allowing a truly comprehensive evaluation of proteomics changes upon the oxidative stimulus.Data are available via ProteomeXchange and SWATHAtlas with the identifiers PXD006802, PXD006802, and PASS01210.

Análise de um problema de crítica textual a propósito de uma passagem sobre os perfumes e o cheiro da terra localizado em Cic. de Orat. 3, 99, referenciado por Plínio em Nat. 13, 21 e Nat. 17, 38. Para esta análise analisam‐se as opiniões expressas por humanistas e estudiosos posteriores e utiliza‐se o primeiro estudo, edição crítica e tradução de uma carta de Celio Calcagnini dirigida a Camilo Vistarini, datada de Buda, em 1518, onde se discute esta passagem de Cícero à luz da sua transmissão e receção em a Naturalis Historia de Plínio.

Staphylococcus aureus biofilm-associated infections are a major public health concern. Current therapies are hampered by reduced penetration of antibiotics through biofilm and low accumulation levels at infected sites, requiring prolonged usage. To overcome these, repurposing antibiotics in combination with nanotechnological platforms is one of the most appealing fast-track and cost-effective approaches. In the present work, we assessed the potential therapeutic benefit of three antibiotics, vancomycin, levofloxacin and rifabutin (RFB), through their incorporation in liposomes. Free RFB displayed the utmost antibacterial effect with MIC and MBIC50 below 0.006 µg/mL towards a methicillin susceptible S. aureus (MSSA). RFB was selected for further in vitro studies and the influence of different lipid compositions on bacterial biofilm interactions was evaluated. Although positively charged RFB liposomes displayed the highest interaction with MSSA biofilms, RFB incorporated in negatively charged liposomes displayed lower MBIC50 values in comparison to the antibiotic in the free form. Preliminary safety assessment on all RFB formulations towards osteoblast and fibroblast cell lines demonstrated that a reduction on cell viability was only observed for the positively charged liposomes. Overall, negatively charged RFB liposomes are a promising approach against biofilm S. aureus infections and further in vivo studies should be performed.

BackgroundCameroon is amongst the worst affected countries by road traffic injuries with an estimated 1443 disability-adjusted life years per 100,000 population. There have been very limited reports on the crucial prehospital response to road traffic injuries in Cameroon. This study aimed to identify prehospital factors associated with RTI mortality in Cameroon.MethodsWe included patients enrolled between June 2022 and March 2023 in the Cameroon Trauma Registry. Information about prehospital factors and demographic data was obtained from patients or their proxies. We examined the association of prehospital care factors like care at the crash scene and type of transportation during crash with final patient outcome. We used Chi-squared test to investigate the association between selected independent variables and mortality. A multivariable logistic regression model was built to identify independent predictors of dying from an RTI.ResultsRTIs constituted 69.5% (n = 3203) of all injuries in the Cameroon Trauma Registry. Only 20.7% (n = 102) of 4 + wheel vehicle occupants had seatbelts on and just 2.7% (n = 53) of motorcycle riders were wearing helmets during the collision. Only 4.9% (n = 156) of patients received any form of scene care. In-hospital mortality was 4.3% (n = 139) and was associated with male sex (AOR = 1.7, 95%CI = 1.08-2.80), crashing on a motorcycle (AOR = 2.08, 95%CI = 1.1-3.67) and scene care (AOR = 0.25, 95%CI = 0.04-0.80).ConclusionsReceiving any type of care at the scene such as bleeding control or being placed in the recovery position by bystanders is associated with improved survival. Improving on existing informal prehospital care responses should be a priority in Cameroon.

IntroductionLittle is known regarding health care seeking behaviors of women in sub-Saharan Africa, specifically Cameroon, who experience violence. The proportion of women who experienced violence enrolled in the Cameroon Trauma Registry (CTR) is lower than expected.MethodsWe concatenated the databases from the October 2017-December 2020 CTR and 2018 Cameroon Demographic and Health Survey (DHS) into a singular database for cross-sectional study. Continuous and categorical variables were compared with Wilcoxon rank-sum and Fisher's exact test. Multivariable logistic regression examined associations between demographic factors and women belonging to the DHS or CTR cohort. We performed additional classification tree and random forest variable importance analyses.Results276 women (13%) in the CTR and 197 (13.1%) of women in the DHS endorsed violence from any perpetrator. A larger percentage of women in the DHS reported violence from an intimate partner (71.6% vs. 42.7%, p

BackgroundAdolescent girls and young woman (AGYW) comprise a significant proportion of new HIV infections and unintended pregnancies in sub-Saharan Africa yet face many barriers to accessing family planning and reproductive health (FPRH) information and services. Developed via human-centered design, the Malkia Klabu ("Queen Club") program aimed to facilitate access to HIV self-testing (HIVST) and FPRH information and products at privately-owned drug shops. We sought to understand barriers and facilitators to program implementation in a 4-month pilot in Tanzania.MethodsForty semi-structured interviews were conducted with participants in a cluster randomized trial of the Malkia Klabu program from November 2019 through March 2020, including 11 with AGYW, 26 with drug shopkeepers, and three with counselors at health facilities to whom AGYW were referred. Interviews were audio-recorded, transcribed, coded, and analyzed to identify key themes. The Consolidated Framework for Implementation Research (CFIR) was used to assess barriers and facilitators to program implementation at multiple levels. CFIR considers the outer setting (e.g., culture and systemic conditions), the inner setting where the intervention is implemented (e.g., incentives, relationships, and available resources), the individuals involved, the innovation as it relates to stakeholder needs, and the implementation process.ResultsThe Malkia Klabu program reshaped and directed the role of drug shopkeepers as providers of information and resources rather than FPRH gatekeepers. Key implementation facilitators included the program's adaptability to a wide range of needs and stages of readiness among AGYW, ability to capitalize on AGYW social networks for driving membership, responsiveness to AGYW's need for privacy, and positive contributions to the income and community standing of drug shopkeepers. Components such as HIVST were highly acceptable to both AGYW and shopkeepers, and the introduction of the loyalty program and HIVST kits in shops opened doors to the provision of FPRH products and information, which was further facilitated by program tools such as videos, product displays, and symbol cards. Although some shopkeepers maintained beliefs that certain contraceptive methods were inappropriate for AGYW, most appeared to provide the products as part of the program.ConclusionsThe Malkia Klabu intervention's success was due in part to its ability to address key motivations of both AGYW and drug shopkeepers, such as maintaining privacy and increasing access to FPRH products for AGYW and increasing business for shops. Better understanding these implementation barriers and facilitators can inform the program's future adaptation and scale-up.Trial registrationclinicaltrials.gov #NCT04045912.

Poly (L-lactic acid) (PLLA) is a biodegradable and biocompatible polymer that has been put forward as a promising material for therapeutic approaches aiming to restore neuronal function. The topographic cues present in PLLA-based scaffolds, defined by the technique used in their preparation, have been shown to play a role on the cellular behavior of adherent cells. Even though this interaction has been shown to influence the regenerative output of the scaffold, there is a lack of studies addressing this response at the proteomic level. Hence, this work focuses on the effect of electrospun PLLA-based nanofibers on the proteome, cellular processes and signaling pathways of SH-SY5Y neuroblastoma cells. It also further explores how these molecular mediators might influence cell proliferation and differentiation upon in vitro culture. For that, mass spectrometry followed by bioinformatics analysis was firstly performed and further complemented with Western blot, cell viability and imaging assays. Results show that PLLA nanofibers differentially activate and inhibit specific cellular functions and signaling pathways related to cell division, apoptosis, actin remodeling, among others. These ultimately block cellular proliferation and induce morphological rearrangements through cytoskeleton remodeling, adaptations that turn cells more prone to differentiate. In synthesis, PLLA nanofibers shift the SH-SY5Y cells proteome towards a state more responsive to differentiation-inductive cues such as the retinoic acid. Unveiling cells responses to nanomaterials is an important step to increase the tools available for their manipulation and potentiate their use in neural tissue engineering. Further studies should be performed to compare the effects of other topographic cues on cellular behavior.