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Background: Cancer patients who are exposed to sepsis and had previous chemotherapy may have increased severity. Among chemotherapeutic agents, anthracyclines have been associated with cardiac toxicity. Like other chemotherapeutic agents, they may cause endothelial toxicity. The aim of this study was to evaluate the effect of anthracycline treatment on the outcome of cancer patients with sepsis. Methods: Data from cancer patients admitted to intensive care units (ICUs) for sepsis or septic shock were extracted from the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique database (1994–2015). Comparison between patients who received anthracycline and those who did not was performed using a propensity score, including confounding variables (age and underlying diseases). A competing risk adjusted for severity of illness (Sequential Organ Failure Assessment [SOFA] score) was used to analyze the duration of vasopressor requirement. Results: Among 2046 patients, 1070 (52.3%) patients who received anthracycline were compared with 976 (47.7%) who did not. The underlying disease was mostly acute hematological malignancy (49.2%). Sepsis, mostly pneumonia (47.7%), had developed 2 days (interquartile range [IQR]:1–4 days) prior to ICU admission. Most patients (n=1156/1980,58.4%) required vasopressors for 3 days (IQR: 2–6 days). Factors associated with the need for vasopressors were aplasia (hazard ratio [HR]=1.72, 95% confidence interval [CI]: 1.21 to 2.47, P=0.002) and day 1 respiratory SOFA score (HR=7.07, 95% CI: 2.75 to 22.1, P

The governance of artisanal gold panning is characterized, in most African countries, by informal practices. The Bili-Uéré Hunting Domain (DCBU), the largest protected area in the Democratic Republic of Congo (60,000 km2), is threatened by artisanal gold mining, the governance of which deserves to be questioned. This article aims to demonstrate how local survival requirements limit the application of national legislation in the governance of gold panning in the said area. To achieve this, data collection mobilized a triple input of methodological instruments including documentation, discourse (individual and group interviews) and direct observation. At the end of the data analysis, the results show that the governance of gold panning in the DCBU is characterized by a coexistence between national regulations and informal practices. This coexistence is due to the local socio-economic needs of the stakeholders, abandoned by the State in its sovereign functions. The actors involved in the governance of gold panning have thus developed systems of relationships around the issues linked to this activity. These results prove that the question of gold panning governance in the DCBU is complex because the stakeholder games are defined at all levels, notably national, provincial and local. At each of these levels, gold panning is based on very structured local governance, governed by the predominance of informal rules. A holistic response from the State and other stakeholders is therefore necessary to reconcile socio-economic concerns with the application of mining and forestry regulations.

Despite increasing recognition of children's right to have a say about matters that affect them (Article 12, United Nations Convention on the Rights of the Child), this right is often denied in the context of child abuse research. This article explores the ways in which ethical decision-making can contribute to the denial of this right and the negative implications of this at both an individual and societal level.Ethical decision-making that stymies the conduct of abuse-focused research with children is usually justified with reference to protecting participants from risk of harm. Whilst in no way suggesting that this is not a critical consideration, the authors question the simplistic and deterministic ways in which this can be understood within ethical decision-making, and the unnecessarily risk-averse decisions that can ensue.Sharing examples from their cumulative 30 years' experience of engaging children and young people in abuse-focused research, the authors stress the need for a more holistic, nuanced and dynamic approach to assessing and managing risk of harm. This would consider risks of both inclusion and exclusion. Understanding that risk and harm are neither static nor universally experienced concepts, it would recognise the implausibility of the ‘do no harm’ guarantees often expected of social researchers. Instead, informed by rights-respecting and trauma-informed perspectives, it would focus on holistically promoting participant wellbeing in, and through, research. Key to this is permitting, and supporting, researchers to exercise contextually-informed, collaborative decision-making in the field; something the authors share their emerging practice framework for.

BackgroundIn the United States, transgender women are disproportionately impacted by HIV and prioritized in the national strategy to end the epidemic. Individual, interpersonal, and structural vulnerabilities underlie HIV acquisition among transgender women and fuel syndemic conditions, yet no nationwide cohort monitors their HIV and other health outcomes. ObjectiveOur objective is to develop a nationwide cohort to estimate HIV incidence, identify risk factors, and investigate syndemic conditions co-occurring with HIV vulnerability or acquisition among US transgender women. The study is informed by the Syndemics Framework and the Social Ecological Model, positing that stigma-related conditions are synergistically driven by shared multilevel vulnerabilities. MethodsTo address logistical and cost challenges while minimizing technology barriers and research distrust, we aim to establish a novel, hybrid community hub–supported digital cohort (N=3000). The digital cohort is the backbone of the study and is enhanced by hubs strategically located across the United States for increased engagement and in-person support. Study participants are English or Spanish speakers, are aged ≥18 years, identify as transgender women or along the transfeminine spectrum, reside in 1 of the 50 states or Puerto Rico, and do not have HIV (laboratory confirmed). Participants are followed for 24 months, with semiannual assessments. These include a questionnaire and laboratory-based HIV testing using self-collected specimens. Using residential zip codes, person-level data will be merged with contextual geolocated data, including population health measures and economic, housing, and other social and structural factors. Analyses will (1) evaluate the contribution of hub support to the digital cohort using descriptive statistics; (2) estimate and characterize syndemic patterns among transgender women using latent class analysis; (3) examine the role of contextual factors in driving syndemics and HIV prevention over time using multilevel regression models; (4) estimate HIV incidence in transgender women and examine the effect of syndemics and contextual factors on HIV incidence using Poisson regression models; and (5) develop dynamic, compartmental models of multilevel combination HIV prevention interventions among transgender women to simulate their impact on HIV incidence through 2030. ResultsEnrollment launched on March 15, 2023, with data collection phases occurring in spring and fall. As of February 24, 2024, a total of 3084 individuals were screened, and 996 (32.3%) met the inclusion criteria and enrolled into the cohort: 2.3% (23/996) enrolled at a hub, and 53.6% (534/996) enrolled through a community hub–supported strategy. Recruitment through purely digital methods contributed 61.5% (1895/3084) of those screened and 42.7% (425/996) of those enrolled in the cohort. ConclusionsStudy findings will inform the development of evidence-based interventions to reduce HIV acquisition and syndemic conditions among US transgender women and advance efforts to end the US HIV epidemic. Methodological findings will also have critical implications for the design of future innovative approaches to HIV research. International Registered Report Identifier (IRRID)DERR1-10.2196/59846

Introduction The Building on Existing Tools to Improve Cancer and Chronic Disease Prevention and Screening in Primary Care (BETTER) programme trains allied health professionals working in primary care settings to develop personalised chronic disease ‘prevention prescriptions’ with patients. However, maintenance of health behaviour changes is difficult without ongoing support. Sustainable options to enhance the BETTER programme and ensure accessibility to underserved populations are needed. We designed the BETTER Women programme, which uses a digital app to match patients with a trained peer health coach (PHC) who provides ongoing support for health behaviour change after receipt of a BETTER prevention prescription in primary care.Methods and analysis We will conduct a type 1 hybrid implementation-effectiveness patient-randomised trial. Interested women aged 40–68 years will be recruited from three large, sociodemographically distinct primary care clinics (urban, suburban and rural). Patients will be randomised 1:1 to intervention or wait-list control after receipt of their BETTER prevention prescription. We will aim to recruit 204 patients per group (408 total). Effectiveness will be assessed by the primary outcome of targeted behaviours achieved for each participant at 6 months, consisting of three cancer screening tests (cervical, breast and colorectal) and four behavioural determinants of cancer and chronic disease (diet, smoking, alcohol use and physical activity). Data will be collected through patient survey and clinical chart review, measured at 3, 6 and 12 months. Implementation outcomes will be assessed through patient surveys and interviews with patients, peer health coaches and healthcare providers. An embedded economic evaluation will examine cost per quality-adjusted life-year and per additional health behavioural targets achieved.Ethics and dissemination This study has been approved by Women’s College Hospital Research Ethics Board (REB), the Royal Victoria Regional Health Centre REB and the University of Toronto REB. All participants will provide informed consent prior to enrolment. Participation is voluntary and withdrawal will have no impact on the usual care received from their primary care provider. The results of this trial will be published in peer-reviewed journals and shared via conference presentations. Deidentified datasets will be shared on request, after publication of results.Trial registration number NCT04746859.

Traumatic abdominal wall hernia is a rare presentation, most commonly reported in the context of motor vehicle accidents and associated with blunt abdominal injuries and handlebar injuries in the pediatric population. A 13-year-old boy presented with multiple traumatic injuries and hemodynamic instability after a high-speed motor vehicle accident. His injuries consisted of massive traumatic abdominal wall hernia (grade 4) with bowel injury and perforation, blunt aortic injury, a Chance fracture, hemopneumothorax, and a humeral shaft fracture. Initial surgical management included partial resection of the terminal ileum, sigmoid colon, and descending colon. Laparostomy was managed with negative pressure wound therapy. The patient underwent skin-only primary closure of the abdominal wall and required multiple returns to theatre for debridement, dressing changes, and repair of other injuries. Various surgical management options for abdominal wall closure were considered. In total, he underwent 36 procedures. The multiple injuries had competing management aims, which required close collaboration between specialist clinicians to form an individualized management plan. The severity and complexity of this injury was of a scale not previously experienced by many clinicians and benefited from intrahospital and interhospital specialist collaboration. The ideal aim of primary surgical repair was not possible in this case of a giant abdominal wall defect.

SARS-CoV-2 infection of immunocompromised individuals often leads to prolonged detection of viral RNA and infectious virus in nasal specimens, presumably due to the lack of induction of an appropriate adaptive immune response. Mutations identified in virus sequences obtained from persistently infected patients bear signatures of immune evasion and have some overlap with sequences present in variants of concern. We characterized virus isolates obtained greater than 100 days after the initial COVID-19 diagnosis from two COVID-19 patients undergoing immunosuppressive cancer therapy, wand compared them to an isolate from the start of the infection. Isolates from an individual who never mounted an antibody response specific to SARS-CoV-2 despite the administration of convalescent plasma showed slight reductions in plaque size and some showed temperature-dependent replication attenuation on human nasal epithelial cell culture compared to the virus that initiated infection. An isolate from another patient—who did mount a SARS-CoV-2 IgM response—showed temperature-dependent changes in plaque size as well as increased syncytia formation and escape from serum-neutralizing antibodies. Our results indicate that not all virus isolates from immunocompromised COVID-19 patients display clear signs of phenotypic change, but increased attention should be paid to monitoring virus evolution in this patient population.

Abstract We performed a cross‐sectional study to determine associations between cognition and MRI‐derived brain outcomes, with obesity, diabetes duration, and metabolic risk factors in 51 Pima American Indians with longstanding type 2 diabetes (T2d) (mean [SD] age: 48.4 [11.3] years, T2d duration: 20.1 [9.1] years). Participants had similar cognition (NIH Toolbox Cognition Battery composite: 45.3 [9.8], p = 0.64, n = 51) compared to normative data. T2d duration, but not other metabolic risk factors, associated with decreased cortical thickness (Point Estimate (PE): −0.0061, 95%CI: −0.0113, −0.0009, n = 45), gray matter volume (PE: −830.39, 95%CI: −1503.14, −157.64, n = 45), and increased white matter hyperintensity volume (PE: 0.0389, 95%CI: 0.0049, 0.0729, n = 45).

Abstract Introduction Adolescent girls and young women (AGYW) living with HIV experience poor HIV outcomes and high rates of unintended pregnancy. Little is known about which healthcare provisions can optimize their HIV‐related outcomes, particularly among AGYW mothers. Methods Eligible 12‐ to 24‐year‐old AGYW living with HIV from 61 health facilities in a South African district completed a survey in 2018–2019 (90% recruited). Analysing surveys and medical records from n = 774 participants, we investigated associations of multiple HIV‐related outcomes (past‐week adherence, consistent clinic attendance, uninterrupted treatment, no tuberculosis [TB] and viral suppression) with seven healthcare provisions: no antiretroviral therapy (ART) stockouts, kind and respectful providers, support groups, short travel time, short waiting time, confidentiality, and safe and affordable facilities. Further, we compared HIV‐related outcomes and healthcare provisions between mothers (n = 336) and nulliparous participants (n = 438). Analyses used multivariable regression models, accounting for multiple outcomes. Results HIV‐related outcomes were poor, especially among mothers. In multivariable analyses, two healthcare provisions were “accelerators,” associated with multiple improved outcomes, with similar results among mothers. Safe and affordable facilities, and kind and respectful staff were associated with higher predicted probabilities of HIV‐related outcomes (p

Abstract The aim of the Protocole National De Diagnostic et de Soins/French National Protocol for Diagnosis and Healthcare (PNDS) is to provide advice for health professionals on the optimum care provision and pathway for patients with glycogen storage disease type III (GSD III).The protocol aims at providing tools that make the diagnosis, defining the severity and different damages of the disease by detailing tests and explorations required for monitoring and diagnosis, better understanding the different aspects of the treatment, defining the modalities and organisation of the monitoring. This is a practical tool, to which health care professionals can refer. PNDS cannot, however, predict all specific cases, comorbidities, therapeutic particularities or hospital care protocols, and does not seek to serve as a substitute for the individual responsibility of the physician in front of his/her patient.

Human tumors progress in part by accumulating epigenetic alterations, which include gains and losses of DNA methylation in different parts of the cancer cell genome. Recent work has revealed a link between these two opposite alterations by showing that DNA hypomethylation in tumors can induce the expression of transcripts that overlap downstream gene promoters and thereby induce their hypermethylation. Preliminary in silico evidence prompted us to investigate if this mechanism applies to the locus harboring AGO1, a gene that plays a central role in miRNA biogenesis and RNA interference. Inspection of public RNA-Seq datasets and RT-qPCR experiments show that an alternative transcript starting 13.4 kb upstream of AGO1 (AGO1-V2) is expressed specifically in testicular germ cells, and becomes aberrantly activated in different types of tumors, particularly in tumors of the esophagus, stomach, and lung. This expression pattern classifies AGO1-V2 into the group of “Cancer-Germline” (CG) genes. Analysis of transcriptomic and methylomic datasets provided evidence that transcriptional activation of AGO1-V2 depends on DNA demethylation of its promoter region. Western blot experiments revealed that AGO1-V2 encodes a shortened isoform of AGO1, corresponding to a truncation of 75 aa in the N-terminal domain, and which we therefore referred to as “∆NAGO1”. Interestingly, significant correlations between hypomethylation/activation of AGO1-V2 and hypermethylation/repression of AGO1 were observed upon examination of tumor cell lines and tissue datasets. Overall, our study reveals the existence of a process of interdependent epigenetic alterations in the AGO1 locus, which promotes swapping between two AGO1 protein-coding mRNA isoforms in tumors.

ObjectiveTo assess the success rate of patent ductus arteriosus (PDA) transcatheter closure in preterm infants and to describe the nature of procedural adverse events and short-term clinical status.Study designAll the preterm infants with PDA transcatheter closure were evaluated retrospectively between July 2019 and March 2023 in a single level III neonatal intensive care unit in France. The procedure was performed in the catheterization laboratory using venous canulation. We retrospectively collected data about the patients' characteristics, procedural outcomes and complications.ResultsTwenty-five infants born between 23.4 and 32.0 weeks of gestational age (mean ± SD 26.3 ± 1.9 weeks) underwent transcatheter PDA closure. Their mean age and weight at the time of the procedure were 52 days (range 22–146 days) and 1,620 g (range 890–3,700 g), respectively. Successful closure was achieved in all but one patient. Procedure related complications were reported in 10 infants (40%), including 6 left pulmonary artery stenosis one of which required a balloon dilatation, two cardiac tamponades and two inferior vena cava thrombosis. Only two post-ligature syndromes occurred after the procedure. Two infants died one of which was related to the procedure.ConclusionTranscatheter closure of a PDA is a valid alternative to surgical ligation due to its high success rate and low incidence of post-ligature syndrome. Nevertheless, we also report rare, although serious complications.

Abstract Autophagy regulates the degradation of damaged organelles and protein aggregates, and is critical for neuronal development, homeostasis, and maintenance, yet few neurodevelopmental disorders have been associated with pathogenic variants in genes encoding autophagy-related proteins. We report three individuals from two unrelated families with a neurodevelopmental disorder characterized by speech and motor impairment, and similar facial characteristics. Rare, conserved, bi-allelic variants were identified in ATG4D, encoding one of four ATG4 cysteine proteases important for autophagosome biogenesis, a hallmark of autophagy. Autophagosome biogenesis and induction of autophagy were intact in cells from affected individuals. However, studies evaluating the predominant substrate of ATG4D, GABARAPL1, demonstrated that three of the four ATG4D patient variants functionally impair ATG4D activity. GABARAPL1 is cleaved or “primed” by ATG4D and an in vitro GABARAPL1 priming assay revealed decreased priming activity for three of the four ATG4D variants. Furthermore, a rescue experiment performed in an ATG4 tetra knockout cell line, in which all four ATG4 isoforms were knocked out by gene editing, showed decreased GABARAPL1 priming activity for the two ATG4D missense variants located in the cysteine protease domain required for priming, suggesting that these variants impair the function of ATG4D. The clinical, bioinformatic, and functional data suggest that bi-allelic loss-of-function variants in ATG4D contribute to the pathogenesis of this syndromic neurodevelopmental disorder.

To investigate the association between enteric pathogens, fecal microbes, and child growth, we conducted a prospective cohort study of 236 children 3 pathogens in their feces. We observed larger increases in height-for-age-z-scores from baseline to the 6-month follow-up among children with Akkermansia muciniphila in their feces (coefficient 0.02 [95% CI 0.0001–0.04]; p = 0.04). Children with Cryptosporidium in their feces had larger declines in weight-for-height/length z-scores from baseline to the 6-month follow-up (coefficient –0.03 [95% CI –0.05 to –0.005]; p = 0.02). Our study showed high prevalence of enteric pathogens among this pediatric cohort and suggests A. muciniphila can potentially serve as a probiotic to improve child growth.

Abstract Background Necrotizing skin and soft tissue infections (NSTIs) are rare but serious and rapidly progressive infections characterized by necrosis of subcutaneous tissue, fascia and even muscle. The care pathway of patients with NSTIs is poorly understood. A better characterization of the care trajectory of these patients and a better identification of patients at risk of a complicated evolution, requiring prolonged hospitalization, multiple surgical re-interventions, or readmission to the intensive care unit (ICU), is an essential prerequisite to improve their care. The main objective of this study is to obtain large-scale data on the care pathway of these patients. We performed a retrospective multicenter observational cohort study in 13 Great Paris area hospitals, including patients hospitalized between January 1, 2015 and December 31, 2019 in the ICU for surgically confirmed NSTIs. Results 170 patients were included. The median duration of stay in ICU and hospital was 8 (3–17) and 37 (14–71) days, respectively. The median time from admission to first surgical debridement was 1 (0–2) day but 69.9% of patients were re-operated with a median of 1 (0–3) additional debridement. Inter-hospital transfer was necessary in 52.4% of patients. 80.2% of patients developed organ failures during the course of ICU stay with 51.8% of patients requiring invasive mechanical ventilation, 77.2% needing vasopressor support and 27.7% renal replacement therapy. In-ICU and in-hospital mortality rates were 21.8% and 28.8%, respectively. There was no significant difference between patients with abdomino-perineal NSTIs (n = 33) and others (n = 137) in terms of in-hospital or ICU mortality. Yet, immunocompromised patients (n = 43) showed significantly higher ICU and in-hospital mortality rates than non-immunocompromised patients (n = 127) (37.2% vs. 16.5%, p = 0.009, and 53.5% vs. 20.5%, p

Despite representing a vast and global concern, the narratives of children who experience child sexual exploitation (CSE) and access associated services are marginalised within research. As an outcome, relatively little is known about how children cope with the impact and consequences of their experiences. This paper draws together methodological insights from researchers reflecting upon three distinct pieces of qualitative fieldwork conducted with children and young people considered ‘vulnerable’ to, and ‘at risk of’, CSE. In doing so, we seek to recognise the challenges encountered when conducting research with vulnerable populations and explore the ‘blurry boundaries’ that researchers tread in order to balance competing power dynamics. This paper will discuss potential safeguarding concerns that arise when conducting sensitive research and will share our experiences of supporting young people to take part in research around child sexual exploitation. We will reflect upon the research process to highlight some of the strategies adopted to enable young people to engage in data collection safely. We consider the dynamic ethical practices that take place in the moment of research encounters, alongside the framework of procedural ethics, to conclude that both are fundamental to enable meaningful participation in research.

Summary: Severe acute malnutrition (SAM) is a multifactorial disease affecting millions of children worldwide. It is associated with changes in intestinal physiology, microbiota, and mucosal immunity, emphasizing the need for multidisciplinary studies to unravel its full pathogenesis. We established an experimental model in which weanling mice fed a high-deficiency diet mimic key anthropometric and physiological features of SAM in children. This diet alters the intestinal microbiota (less segmented filamentous bacteria, spatial proximity to epithelium), metabolism (decreased butyrate), and immune cell populations (depletion of LysoDC in Peyer’s patches and intestinal Th17 cells). A nutritional intervention leads to a fast zoometric and intestinal physiology recovery but to an incomplete restoration of the intestinal microbiota, metabolism, and immune system. Altogether, we provide a preclinical model of SAM and have identified key markers to target with future interventions during the education of the immune system to improve SAM whole defects.

Recent data protection regulatory frameworks, such as the Protection of Personal Information Act (POPI Act) in South Africa and the General Data Protection Regulation (GDPR) in the European Union, impose governance requirements for research involving high-risk and vulnerable groups such as children and adolescents. Our paper's objective is to unpack what constitutes adequate safeguards to protect the personal information of vulnerable populations such as children and adolescents. We suggest strategies to adhere meaningfully to the principal aims of data protection regulations. Navigating this within established research projects raises questions about how to interpret regulatory frameworks to build on existing mechanisms already used by researchers. Therefore, we will explore a series of best practices in safeguarding the personal information of children, adolescents and young people (0-24 years old), who represent more than half of sub-Saharan Africa's population. We discuss the actions taken by the research group to ensure regulations such as GDPR and POPIA effectively build on existing data protection mechanisms for research projects at all stages, focusing on promoting regulatory alignment throughout the data lifecycle. Our goal is to stimulate a broader conversation on improving the protection of sensitive personal information of children, adolescents and young people in sub-Saharan Africa. We join this discussion as a research group generating evidence influencing social and health policy and programming for young people in sub-Saharan Africa. Our contribution draws on our work adhering to multiple transnational governance frameworks imposed by national legislation, such as data protection regulations, funders, and academic institutions.

Se realizó un estudio transversal en estudiantes de Medicina de una universidad privada de Lima. El objetivo fue describir el nivel de conocimientos y las actitudes sobre la COVID-19, además de su percepción sobre el rol de los medios de comunicación y de las redes sociales. El 32% no sabía que en los primeros cinco días de la enfermedad, las pruebas serológicas son preferibles para diagnosticar la COVID-19, comparadas con las pruebas moleculares; el 73% reportó estar dispuesto a trabajar como voluntario durante la pandemia y el 94% recibió información falsa sobre la COVID-19 en las redes sociales. Este estudio demuestra que la información sobre el uso de pruebas diagnósticas debe ser reforzada y que se debe tomar en cuenta el alto porcentaje de estudiantes dispuestos a ser voluntarios durante la pandemia de la COVID-19.

Early motherhood can negatively impact health, educational, and socio-economic outcomes for adolescent mothers and their children. Supporting adolescent mothers’ educational attainment, and timely return to school, may be key to interrupting intergenerational cycles of adversity. Yet, there remains a paucity of evidence on the factors that are associated with mothers’ postpartum return to school and the mediators of this process, particularly across sub-Saharan Africa where adolescent pregnancy rates remain high . This paper is based on interviews with 1,046 adolescent mothers from South Africa. Mothers who had returned to school after birth showed lower poverty, fewer repeated grades preceding the pregnancy, continued schooling during pregnancy, higher daycare/crèche use, more family childcare support, and lower engagement in exclusive breastfeeding within six months postpartum. Mediation analyses showed that lower poverty was directly associated with school return and via two indirect pathways: continued schooling during pregnancy and using daycare/crèche services. This study demonstrates that lacking childcare constitutes a major hurdle to mothers’ school return which needs to be addressed in addition to socioeconomic and individual-level barriers. Policy makers and practitioners should consider supporting young mothers with combination interventions which include services supporting school retention during pregnancy and access to, and financial supplements for, daycare.

Background The intergenerational effects of HIV require long-term investigation. We compared developmental outcomes of different generations impacted by HIV—children of mothers not living with HIV, the ‘second generation’ (ie, with recently infected mothers) and the ‘third generation’ (ie, children of perinatally infected mothers).Methods A cross-sectional community sample of N=1015 young mothers (12–25 years) and their first children (2–68 months, 48.2% female), from South Africa’s Eastern Cape Province. 71.3% (n=724) of children were born to mothers not living with HIV; 2.7% (n=27; 1 living with HIV) were third-generation and 26.0% (n=264; 11 living with HIV) second-generation children. Child scores on the Mullen Scales of Early Learning (MSEL), the WHO Ten Questions Screen for Disability and maternal demographics were compared between groups using χ2 tests and univariate approach, analysis of variance analysis. Hierarchical linear regressions investigated predictive effects of familial HIV infection patterns on child MSEL composite scores, controlling for demographic and family environment variables.Results Second-generation children performed poorer on gross (M=47.0, SD=13.1) and fine motor functioning (M=41.4, SD=15.2) and the MSEL composite score (M=90.6, SD=23.0) than children with non-infected mothers (gross motor: M=50.4, SD=12.3; fine motor: M=44.4, SD=14.1; composite score: M=94.1, SD=20.7). The third generation performed at similar levels to non-exposed children (gross motor: M=52.4, SD=16.1; fine motor: M=44.3, SD=16.1, composite score: M=94.7, SD=22.2), though analyses were underpowered for definite conclusions. Hierarchical regression analyses suggest marginal predictive effects of being second-generation child compared with having a mother not living with HIV (B=−3.3, 95% CI=−6.8 to 0 .1) on MSEL total scores, and non-significant predictive effects of being a third-generation child (B=1.1, 5% CI=−7.5 to 9.7) when controlling for covariates. No group differences were found for disability rates (26.9% third generation, 27.7% second generation, 26.2% non-exposed; χ2=0.02, p=0.90).Conclusion Recently infected mothers and their children may struggle due to the disruptiveness of new HIV diagnoses and incomplete access to care/support during pregnancy and early motherhood. Long-standing familial HIV infection may facilitate care pathways and coping, explaining similar cognitive development among not exposed and third-generation children. Targeted intervention and fast-tracking into services may improve maternal mental health and socioeconomic support.

Abstract The objective of this study was to investigate the association between dietary diversity, child growth and child developmental outcomes. This was a prospective cohort study. Developmental outcomes were assessed by communication, fine motor, gross motor, personal social, problem solving and combined developmental scores measured by the Extended Ages and Stages Questionnaire (EASQ) at a 6‐month follow‐up visit. Height and weight were measured at baseline and a 6‐month follow‐up. Baseline minimum dietary diversity (MDD) for children 6–23 months old was defined by consumption of five or more of the following food groups: (1) breast milk; (2) grains, roots and tubers; (3) legumes and nuts; (4) dairy products; (5) flesh foods; (6) eggs; (7) vitamin A‐rich fruits and vegetables and (8) other fruits and vegetables. Participants were 117 children 6–23 months of age. Linear growth faltering was defined as a significant decline (p

Abstract Estimating animal abundance and density are fundamental goals of many wildlife monitoring programs. Camera trapping has become an increasingly popular tool to achieve these monitoring goals due to recent advances in modeling approaches and the capacity to simultaneously collect data on multiple species. However, estimating the density of unmarked populations continues to be problematic due to the difficulty in implementing complex modeling approaches, low precision of estimates, and absence of rigor in testing of model assumptions and their influence on results. Here, we describe a novel approach that uses still image camera traps to estimate animal density without the need for individual identification, based on the time spent in front of the camera (TIFC). Using results from a large‐scale multispecies monitoring program with nearly 3000 cameras deployed over 6 years in Alberta, Canada, we provide a reproducible methodology to estimate parameters and we test key assumptions of the TIFC model. We compare moose (Alces alces) density estimates from aerial surveys and TIFC, including incorporating correction factors for known TIFC assumption violations. The resulting corrected TIFC density estimates are comparable to aerial density estimates. We discuss the limitations of the TIFC method and areas needing further investigation, including the need for long‐term monitoring of assumption violations and the number of cameras necessary to provide precise estimates. Despite the challenges of assumption violations and high measurement error, cameras and the TIFC method can provide useful alternative or complementary animal density estimates for multispecies monitoring when compared to traditional monitoring methods.

BackgroundSome children born to adolescent mothers may have developmental challenges, while others do not. Research focusing on which children of adolescent mothers are at the highest risk for cognitive delay is still required. Both maternal HIV status and maternal mental health may affect child development. An examination of maternal mental health, especially in the presence of maternal HIV infection may be timely. This study explores the relationship between the mental health of adolescent mothers (comparing those living with and not living with HIV) and the cognitive development performance scores of their children. Additional possible risk and protective factors for poor child development are explored to identify those children born to adolescent mothers who may be at the greatest risk of poor cognitive development.MethodsCross-sectional data utilised within the analyses was drawn from a large cohort of adolescent mothers and their children residing in South Africa. Detailed study questionnaires were completed by adolescent mothers relating to their self and their child and, standardised cognitive assessments were completed by trained researchers for all children using in the Mullen Scales of Early Learning. Chi-square, t-tests (Kruskal Wallis tests, where appropriate), and ANOVA were used to explore sample characteristics and child cognitive development scores by maternal mental health status (operationalised as likely common mental disorder) and combined maternal mental health and HIV status. Multivariable linear regression models were used to explore the relationship between possible risk factors (including poor maternal mental health and HIV) and, child cognitive development scores.ResultsThe study included 954 adolescent mothers; 24.1% (230/954) were living with HIV, 12.6% (120/954) were classified as experiencing likely common mental disorder. After adjusting for covariates, maternal HIV was found to be associated with reduced child gross motor scores (B = -2.90 [95%CI: -5.35, -0.44], p = 0.02), however, no other associations were identified between maternal likely common mental disorder, or maternal HIV status (including interaction terms), and child cognitive development scores. Sensitivity analyses exploring individual maternal mental health scales identified higher posttraumatic stress symptomology scores as being associated with lower child cognitive development scores. Sensitivity analyses exploring potential risk and protective factors for child cognitive development also identified increased maternal educational attainment as being protective of child development scores, and increased child age as a risk factor for lower development scores.ConclusionsThis study addresses a critical evidence gap relating to the understanding of possible risk factors for the cognitive development of children born to adolescent mothers affected by HIV. This group of mothers experience a complex combination of risk factors, including HIV, likely common mental disorder, and structural challenges such as educational interruption. Targeting interventions to support the cognitive development of children of adolescent mothers most at risk may be of benefit. Clearly a basket of interventions needs to be considered, such as the integration of mental health provision within existing services, identifying multiple syndemics of risk, and addressing educational and structural challenges, all of which may boost positive outcomes for both the mother and the child.

The Sustainable Development Goals (SDGs) are a visionary and multi-sectoral agenda for human development. With less than a decade left to reach these targets, it is important to identify those at greatest risk of not meeting these ambitious targets. Adolescent mothers and their children are a highly vulnerable group. We mapped 35 SGD-related targets among 1,046 adolescent mothers and their oldest child (n = 1046). Questionnaires using validated scales were completed by 10- to 24-year-old adolescent girls and young women who had their first child before age 20 in an HIV-endemic district in the Eastern Cape province of South Africa. Maternal outcomes included 26 SDG-aligned indicators, while child-related outcomes included 9 indicators. Data was collected by trained researchers, following informed voluntary consent by the adolescent mothers and their caregivers. Frequencies and chi-square tests were conducted to compare progress along SDG-aligned indicators among adolescent mothers by HIV status. Overall, adolescent mothers reported low attainment of SDG-aligned indicators. While four in five adolescent mothers lived in poor households, nearly 93% accessed at least one social cash transfer and 80% accessed a child support grant for their children. Food security rates among adolescent mothers (71%) were lower than among their children (91%). Only two-thirds of adolescent mothers returned to school after childbirth, and only one-fifth were either studying or employed. Over half of adolescent mothers had experienced at least one type of violence (domestic, sexual or community). HIV-positive status was associated with higher rates of hunger and substance use, poorer school attendance, and higher rates of exposure to violence. Understanding progress and gaps in meeting the SDGs among highly vulnerable groups is critical, particularly for adolescent mothers and their children. These complex vulnerabilities suggest that programming for adolescent mothers must address their unique needs.

It is unclear which patient-reported outcome measures (PROMs) can assess non-operative care for scoliosis. Most existing tools aim to assess the effects of surgery. This scoping review aimed to inventory the PROMs used to assess non-operative scoliosis treatment by population and languages. We searched Medline (OVID) as per COSMIN guidelines. Studies were included if patients were diagnosed with idiopathic scoliosis or adult degenerative scoliosis and used PROMs. Studies without quantitative data or reporting on fewer than 10 participants were excluded. Nine reviewers extracted the PROMs used, the population(s), language(s), and study setting(s). We screened 3724 titles and abstracts. Of these, the full texts of 900 articles were assessed. Data were extracted from 488 studies, in which 145 PROMs were identified across 22 languages and 5 populations (Adolescent Idiopathic Scoliosis, Adult Degenerative Scoliosis, Adult Idiopathic Scoliosis, Adult Spine Deformity, and an Unclear category). Overall, the most used PROMs were the Oswestry Disability Index (ODI, 37.3%), Scoliosis Research Society-22 (SRS-22, 34.8%), and the Short Form-36 (SF-36, 20.1%), but the frequency varied by population. It is now necessary to determine the PROMs that demonstrate the best measurement properties in the non-operative treatment of scoliosis to include in a core set of outcomes.

Protein citrullination (PC) is a posttranslational modification (PTM) that converts a peptidyl arginine into a peptidyl citrulline. Aberrant PC is a hallmark of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease, prion disease, and multiple sclerosis. Common among these diseases is a dramatic increase of PC in reactive astrocytes. Some citrullinated proteins have been identified. The most prominent are astrocytic cytoskeletal proteins such as GFAP and vimentin, and myelin protein MBP. Recent investigation in ALS has revealed new changes, including a decreased PC in neurons and an association of PC with myelin protein aggregates. These findings suggest that PC contributes to protein aggregation, neuronal dysfunction, neuroinflammation, and axonal degeneration. However, how PC impact neurodegeneration remains to be understood. Further studies are needed to understand a range of questions, from how PC modulates individual protein functions to its impact on diseases. Because of the PC's robust changes in neurodegenerative diseases, there are also prospects that this PTM may be harnessed as biomarkers, and modulation of this PTM may be an avenue for therapy. In this review, we summarize the current understanding of PC in ALS and other neurodegenerative diseases, the investigative methods for PC, and PC's potential as a biomarker and a therapeutic target.

Background: Bleeding and thrombosis induce major morbidity and mortality in patients under extracorporeal membrane oxygenator (ECMO). Circuit changes can be performed for oxygenation membrane thrombosis but are not recommended for bleeding under ECMO. The objective of this study was to evaluate the course of clinical, laboratory, and transfusion parameters before and after ECMO circuit changes warranted by bleeding or thrombosis., Methods: In this single-center, retrospective, cohort study, clinical parameters (bleeding syndrome, hemostatic procedures, oxygenation parameters, transfusion) and laboratory parameters (platelet count, hemoglobin, fibrinogen, PaO 2 ) were collected over the seven days surrounding the circuit change., Results: In the 274 patients on ECMO from January 2017 to August 2020, 48 circuit changes were performed in 44 patients, including 32 for bleeding and 16 for thrombosis. Mortality was similar in the patients with vs. without changes (21/44, 48% vs. 100/230, 43%) and in those with bleeding vs. thrombosis (12/28, 43% vs. 9/16, 56%, P = 0.39). In patients with bleeding, numbers of bleeding events, hemostatic procedures, and red blood cell transfusions were significantly higher before vs. after the change (P < 0.001); the platelet counts and fibrinogen levels decreased progressively before and increased significantly after the change. In patients with thrombosis, numbers of bleeding events and red blood cell transfusions did not change after membrane change. No significant differences were demonstrated between oxygenation parameters (ventilator FiO 2 , ECMO FiO 2 , and PaO 2 ) and ECMO flow before vs. after the change., Conclusions: In patients with severe and persistent bleeding, changing the ECMO circuit decreased clinical bleeding and red blood cell transfusion needs and increased platelets and fibrinogen levels. Oxygenation parameters did not change significantly in the group with thrombosis., (© 2023. The Author(s).)