New approaches in the diagnosis and treatment of latent tuberculosis infection

With nearly 9 million new active disease cases and 2 million deaths occurring worldwide every year, tuberculosis continues to remain a major public health problem. Exposure to Mycobacterium tuberculosis leads to active disease in only ~10% people. An effective immune response in remaining individuals stops M. tuberculosis multiplication. However, the pathogen is completely eradicated in ~10% people while others only succeed in containment of infection as some bacilli escape killing and remain in non-replicating (dormant) state (latent tuberculosis infection) in old lesions. The dormant bacilli can resuscitate and cause active disease if a disruption of immune response occurs. Nearly one-third of world population is latently infected with M. tuberculosis and 5%-10% of infected individuals will develop active disease during their life time. However, the risk of developing active disease is greatly increased (5%-15% every year and ~50% over lifetime) by human immunodeficiency virus-coinfection. While active transmission is a significant contributor of active disease cases in high tuberculosis burden countries, most active disease cases in low tuberculosis incidence countries arise from this pool of latently infected individuals. A positive tuberculin skin test or a more recent and specific interferon-gamma release assay in a person without overt signs of active disease indicates latent tuberculosis infection. Two commercial interferon-gamma release assays, QFT-G-IT and T-SPOT.TB have been developed. The standard treatment for latent tuberculosis infection is daily therapy with isoniazid for nine months. Other options include therapy with rifampicin for 4 months or isoniazid + rifampicin for 3 months or rifampicin + pyrazinamide for 2 months or isoniazid + rifapentine for 3 months. Identification of latently infected individuals and their treatment has lowered tuberculosis incidence in rich, advanced countries. Similar approaches also hold great promise for other countries with low-intermediate rates of tuberculosis incidence

Children’s subjective well-being: Multi-group analysis among a sample of children from two socio-economic status groups in the Western Cape, South Africa

Recent advancements in child well-being research have shown an increased importance of subjective well-being in understanding children and adolescents’ quality of life. These advancements have raised questions concerning the extent to which children’s subjective perceptions and experiences of well-being can be compared between countries and across diverse cultures. With a dearth of empirical data on cross-cultural comparisons, the validation of existing measures and cross-cultural comparisons have been identified by a number of researchers as critical in contributing to this process, and ultimately to the international dialogue on children’s overall quality of life. The aim of the current study was to test two measures of subjective well-being (the Students’ Life Satisfaction Scale and the Personal Well-Being Index-School Children) among a sample of children in the Western Cape region of South Africa. Noting the diversity of living experiences between children from different socio-economic status groups in South Africa, the study further aimed to determine the extent to which the measures are comparable across socio-economic status groups. Data from the first wave of the Children’s World Survey were used; and included a sample of 1004 12 year old children randomly selected from 15 schools within the Cape Town Metropole. Located within the goodness of fit theoretical framework, confirmatory factor analysis and structural equation modelling was used to test the overall fit structure; while multi-group factor analysis was used to test measurement invariance across socio-economic status groups. The results show appropriate fit structure for the overall model, with metric and scalar factor invariance tenable across socio-economic status groups. The overall findings suggest that the two measures are appropriate for use with children from low and middle socio-economic status groups in the Western Cape province of South Africa and that the two groups can be compared by correlations, regressions and means.IS

ICAR: endoscopic skull‐base surgery

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Dating the geologic history of Oman's Semail ophiolite: insights from U-Pb geochronology

Eclogites from the deepest structural levels beneath the Semail ophiolite, Oman, record the subduction and later exhumation of the Arabian continental margin. Published ages for this high pressure event reveal large discrepancies between the crystallisation ages of certain eclogite-facies minerals and apparent cooling ages of micas. We present precise U-Pb zircon (78.95 ± 0.13 Ma) and rutile (79.6 ± 1.1 Ma) ages for the eclogites, as well as new U-Pb zircon ages for trondhjemites from the Semail ophiolite (95.3 ± 0.2 Ma) and amphibolites from the metamorphic sole (94.48 ± 0.23 Ma). The new eclogite ages reinforce published U-Pb zircon and Rb-Sr mineral-whole rock isochron ages, yet are inconsistent with published interpretations of older 40Ar/39Ar phengite and Sm-Nd garnet dates. We show that the available U-Pb and Rb-Sr ages, which are in tight agreement, fit better with the available geological evidence, and suggest that peak metamorphism of the continental margin occurred during the later stages of ophiolite emplacement

Sclareol antagonizes the sedative effect of diazepam in thiopental sodium-induced sleeping animals: In vivo and in silico studies

Background: Sclareol (SCL), a labdane diterpene compound found in Salvia sclarea L., exhibited therapeutic effects. This study investigated the potential interaction between SCL and diazepam (DZP) in modulating sedation in the thiopental sodium-induced sleeping animal model, supported by in-silico molecular docking analysis. Methods: The control, sclareol (5, 10 and 20 mg/kg), and the reference drugs [diazepam: 3 mg/kg and Caffeine (CAF): 10 mg/kg] were used in male albino mice. Then, sodium thiopental (40 mg/kg, i.p.) was administrated to induce sleep. The latent period, percentage of sleep incidence and modulation of latency were measured. Further, homology modeling of human γ-aminobutyric acid (GABA) was conducted examine the binding mode of GABA interaction with SCL, DZP, and CAF compounds Results: SCL (low dose) slightly increased the sleep latency, while the higher dose significantly prolonged sleep latency. DZP, a GABAA receptor agonist, exhibited strong sleep-inducing properties, reducing sleep latency, and increasing sleeping time. Caffeine (CAF) administration prolonged sleep latency and reduced sleeping time, consistent with its stimulant effects. The combination treatments involving SCL, DZP, and CAF showed mixed effects on sleep parameters. The molecular docking revealed good binding affinities of SCL, DZP, and CAF for GABAA receptor subunits A2 and A5. Conclusions: Our findings highlighted the complex interplay between SCL, DZP, and CAF in regulating sleep behaviors and provided insights into potential combination therapies for sleep disorders