Novel Function of Phosphoinositide 3-Kinase in T Cell Ca\u3csup\u3e2+\u3c/sup\u3e Signaling

This study presents evidence that phosphoinositide (PI) 3-kinase is involved in T cell Ca2+ signaling via a phosphatidylinositol 3,4,5-trisphosphate PI(3,4,5)P3-sensitive Ca2+entry pathway. First, exogenous PI(3,4,5)P3 at concentrations close to its physiological levels induces Ca2+ influx in T cells, whereas PI(3,4)P2, PI(4,5)P2, and PI(3)P have no effect on [Ca2+]i. This Ca2+ entry mechanism is cell type-specific as B cells and a number of cell lines examined do not respond to PI(3,4,5)P3 stimulation. Second, inhibition of PI 3-kinase by wortmannin and by overexpression of the dominant negative inhibitor Δp85 suppresses anti-CD3-induced Ca2+response, which could be reversed by subsequent exposure to PI(3,4,5)P3. Third, PI(3,4,5)P3 is capable of stimulating Ca2+ efflux from Ca2+-loaded plasma membrane vesicles prepared from Jurkat T cells, suggesting that PI(3,4,5)P3 interacts with a Ca2+ entry system directly or via a membrane-bound protein. Fourth, although D-myo-inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4) mimics PI(3,4,5)P3 in many aspects of biochemical functions such as membrane binding and Ca2+ transport, we raise evidence that Ins(1,3,4,5)P4 does not play a role in anti-CD3- or PI(3,4,5)P3-mediated Ca2+ entry. This PI(3,4,5)P3-stimulated Ca2+ influx connotes physiological significance, considering the pivotal role of PI 3-kinase in the regulation of T cell function. Given that PI 3-kinase and phospholipase C-γ form multifunctional complexes downstream of many receptor signaling pathways, we hypothesize that PI(3,4,5)P3-induced Ca2+ entry acts concertedly with Ins(1,4,5)P3-induced Ca2+ release in initiating T cell Ca2+ signaling. By using a biotinylated analog of PI(3,4,5)P3 as the affinity probe, we have detected several putative PI(3,4,5)P3-binding proteins in T cell plasma membranes

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Body appreciation around the world: Measurement invariance of the Body Appreciation Scale-2 (BAS-2) across 65 nations, 40 languages, gender identities, and age

The Body Appreciation Scale-2 (BAS-2) is a widely used measure of a core facet of the positive body image construct. However, extant research concerning measurement invariance of the BAS-2 across a large number of nations remains limited. Here, we utilised the Body Image in Nature (BINS) dataset - with data collected between 2020 and 2022 - to assess measurement invariance of the BAS-2 across 65 nations, 40 languages, gender identities, and age groups. Multi-group confirmatory factor analysis indicated that full scalar invariance was upheld across all nations, languages, gender identities, and age groups, suggesting that the unidimensional BAS-2 model has widespread applicability. There were large differences across nations and languages in latent body appreciation, while differences across gender identities and age groups were negligible-to-small. Additionally, greater body appreciation was significantly associated with higher life satisfaction, being single (versus being married or in a committed relationship), and greater rurality (versus urbanicity). Across a subset of nations where nation-level data were available, greater body appreciation was also significantly associated with greater cultural distance from the United States and greater relative income inequality. These findings suggest that the BAS-2 likely captures a near-universal conceptualisation of the body appreciation construct, which should facilitate further cross-cultural research

Stryphnodendron adstringens and purified tannin on Pythium insidiosum: in vitro and in vivo studies

BACKGROUND: Pythium insidiosum is the etiological agent of pythiosis, an emerging life-threatening infectious disease in tropical and subtropical regions. The pathogen is a fungus-like organism resistant to antifungal therapy, for this reason, most cases need extensive surgical debridments as treatment, but depending on the size and anatomical region of the lesion, such approach is unfeasible. We investigate the fungicidal effect and toxicity of crude bark extract of Stryphnodendron adstringens and commercially available tannin on Pythium insidiosum both in vitro and in vivo. METHODS: Standardized fragments of mycelia of fifteen isolates of P. insidiosum were tested with different concentrations of bark extract (10 to 30% v/v) and tannin (0.5, 1.0 and 1.5 mg/mL). For in vivo study, fifteen rabbits were experimentally infected with zoospores of P. insidiosum and treated by oral and intralesional applications of bark extract and tannin. Acute toxicity tests with both substances were also performed in rats. RESULTS: In vitro studies showed fungicidal effect for both substances at different concentrations and the SEM showed alteration on the cell wall surface of the pathogen. All infected rabbits developed a firm nodular mass that reached around 90 mm(2) ninety days after inoculation, but neither the intralesional inoculation of tannin, nor the oral administration of crude extract and tannin were able to promote remission of the lesions. CONCLUSIONS: Lesions developed by rabbits presented an encapsulated abscess being quite different of naturally acquired pythiosis, which is characterized by ulcerated lesions. Since no toxicity was observed in rats or rabbits inoculated with these products, while in vitro experiments showed direct antifungal effect, therapeutic activity of S. adstringens and tannin should be clinically tested as an alternative for healing wounds in naturally acquired pythiosis

Work organization and the health of bank employees Organización del trabajo y salud de empleados del banco Organização do trabalho e saúde de trabalhadores bancários

The Brazilian banking sector has undergone an intense restructuring process and taken a leading position in the incorporation of new technologies and organizational innovations. Computerization in the industry, in association with forms of work organization, has resulted in changes that reflect on the workers' health. Based on the theoretical and methodological frameworks of historical and dialectical materialism, this qualitative study investigates the work conditions of bank employees in order to identify the extent to which changes in work organization interfere with these workers' health. Data were collected through interviews held with 11 bank employees. In addition to physical sickening due to occupational diseases directly related to work intensification, the results also show an increased incidence of mental suffering and a feeling of loss of professional identity. Work-related frustration, instability and concerns related to psychological pressure resulting from the need to achieve goals predominated in the reports.<br>La Banca Brasileña pasó por un intenso proceso de reestructuración y ha ocupado posiciones de liderazgo en la incorporación de nuevas tecnologías e innovaciones organizacionales. La informatización de la industria, junto con nuevas maneras de organización del trabajo, dio lugar a cambios que reflejaron en la salud de los trabajadores. Con base en el marco teórico y metodológico del materialismo histórico y dialéctico, este estudio cualitativo tuvo como objetivo investigar las condiciones laborales de los empleados del banco para identificar el grado en que los cambios en la organización del trabajo influyeron en la salud de los trabajadores. Los datos fueron recolectados a través de entrevistas con once empleados del banco. Los resultados mostraron, además de las enfermedades físicas profesionales directamente relacionadas con la intensificación del trabajo, aumento de la incidencia de sufrimiento mental y la sensación de pérdida de identidad profesional. Predominaron en las entrevistas sentimientos de frustración e inseguridad sobre el trabajo y la preocupación por la presión psicológica de la necesidad de logro de los objetivos.<br>O setor bancário brasileiro passou por intenso processo de reestruturação e ocupou posição de liderança na incorporação de novas tecnologias e inovações organizacionais. A informatização do setor, aliada às novas formas de organizar o trabalho, resultou em mudanças que refletiram na saúde dos trabalhadores. Fundamentado no referencial teórico metodológico do materialismo histórico-dialético, este estudo, de caráter qualitativo, teve por objetivo investigar as condições de trabalho de bancários, para identificar em que medida as mudanças na organização do trabalho interferiram na saúde daqueles trabalhadores. Os dados foram coletados através de entrevistas com onze bancários. Os resultados revelaram, além de adoecimentos de ordem física por doenças ocupacionais, diretamente relacionadas à intensificação do trabalho, o aumento da incidência de sofrimento mental e sentimento de perda de identidade profissional. Predominaram, nos depoimentos, sentimentos de frustração e insegurança em relação ao trabalho e preocupação com a pressão psicológica, derivada da necessidade de cumprimento de metas