Explore the vast range of titles available.

Introduction The objective of this scoping review was to understand the methods, extent and type of evidence in relation to the use of simulation or SIM-based medical education pedagogies to teach biomedical sciences to undergraduate medical students in accredited medical schools, globally. The review considers literature published between 2014 and 2024. Inclusion criteria The review only considered reports about populations of students enrolled in accredited undergraduate medical education programs that train medical doctors, including DO/MD/MBBS/MBChB or equivalents in any country. Simulation, as a concept, is considered as reportedly used in the context of teaching knowledge, skills, or practice-related attitudes in biomedical science disciplines. Articles published in the English Language were considered. Methods An initial search of the Cochrane and the Joanna Briggs Institute’s [JBI] Evidence-based Practice databases in October 2023 found no similar review. For this review, the primary databases searched included PubMed, ERIC, and Google Scholar. The JBI [Joanna Briggs Institute] SUMARI was the platform for screening, approval, extraction, synthesis, and review. For screening and appraisal, two members of the review team were required to approve an article. Results A total of 18 articles were considered for this review out of the initial yield of 2,671. These included: 4 Analytical Cross-Sectional Studies- 2 from Australia, 1 from the USA, and 1 from China; 2 Systematic Review and Research Syntheses; 3 Randomized Controlled Trials- 1 from China and 2 from Italy; 6 Quasi-Experimental Studies- 1 from Taiwan, 1 from the Netherlands, 1 from the both China and United Kingdom, 1 from Sweden, 1 from Indonesia and 1 from the United States; and 3 Text and Opinion Studies. Findings highlight the growing use of simulation and technology-enhanced learning in medical education, improving competency, retention, and engagement. Simulation, aided by VR, AR, and PBL, enhances motivation and skills but cannot fully replace hands-on training. Limitations include inconsistent assessment impacts, cost challenges, and accessibility concerns. Conclusion Simulation and technology-enhanced learning improve engagement, skills, and retention in medical education. Integration with traditional methods maximizes effectiveness. Virtual simulations aided by technologies, VR or AR offer immersive experiences but require careful implementation.

Chlamydia trachomatis is an obligate intracellular pathogen with global health and economic impact. Upon infection, C. trachomatis resides within a protective niche, the inclusion, wherein it replicates and usurps host cell machinery and resources. The inclusion membrane is the key host-pathogen interface that governs specific protein-protein interactions to manipulate host signaling pathways. At the conclusion of the infection cycle, C. trachomatis exits the host cell via lysis or extrusion. Extrusion depends on the phosphorylation state of myosin light chain 2 (MLC2); the extent of phosphorylation is determined by the ongoing opposing activities of myosin phosphatase (MYPT1) and myosin kinase (MLCK). Previously, it was shown that MYPT1 is recruited to the inclusion and interacts with CT228 for regulation of host cell egress. In this study, we generated a targeted chromosomal mutation of CT228 (L2-ΔCT228) using the TargeTron system and demonstrate a loss of MYPT1 recruitment and increase in extrusion production in vitro . Mutation of CT228 did not affect chlamydial growth in cell culture or recruitment of MLC2. Moreover, we document a delay in clearance of L2-ΔCT228 during murine intravaginal infection as well as a reduction in systemic humoral response, relative to L2-wild type. Taken together, the data suggest that loss of MYPT1 recruitment (as a result of CT228 disruption) regulates the degree of host cell exit via extrusion and affects the longevity of infection in vivo .

[This corrects the article DOI: 10.3389/fcimb.2018.00415.].

Hydrogen sulfide (H 2 S) is a respiratory toxicant that creates extreme environments tolerated by few organisms. H 2 S is also produced endogenously by metazoans and plays a role in cell signaling. The mechanisms of H 2 S toxicity and its physiological functions serve as a basis to discuss the multifarious strategies that allow animals to survive in H 2 S-rich environments. Despite their toxicity, H 2 S-rich environments also provide ecological opportunities, and complex selective regimes of covarying abiotic and biotic factors drive trait evolution in organisms inhabiting H 2 S-rich environments. Furthermore, adaptation to H 2 S-rich environments can drive speciation, giving rise to biodiversity hot spots with high levels of endemism in deep-sea hydrothermal vents, cold seeps, and freshwater sulfide springs. The diversity of H 2 S-rich environments and their inhabitants provides ideal systems for comparative studies of the effects of a clear-cut source of selection across vast geographic and phylogenetic scales, ultimately informing our understanding of how environmental stressors affect ecological and evolutionary processes.

Extreme environments test the limits of life; yet, some organisms thrive in harsh conditions. Extremophile lineages inspire questions about how organisms can tolerate physiochemical stressors and whether the repeated colonization of extreme environments is facilitated by predictable and repeatable evolutionary innovations. We identified the mechanistic basis underlying convergent evolution of tolerance to hydrogen sulfide (H₂S)—a toxicant that impairs mitochondrial function—across evolutionarily independent lineages of a fish (Poecilia mexicana, Poeciliidae) from H₂S-rich springs. Using comparative biochemical and physiological analyses, we found that mitochondrial function is maintained in the presence of H₂S in sulfide spring P. mexicana but not ancestral lineages from nonsulfidic habitats due to convergent adaptations in the primary toxicity target and a major detoxification enzyme. Genome-wide local ancestry analyses indicated that convergent evolution of increased H₂S tolerance in different populations is likely caused by a combination of selection on standing genetic variation and de novo mutations. On a macroevolutionary scale, H₂S tolerance in 10 independent lineages of sulfide spring fishes across multiple genera of Poeciliidae is correlated with the convergent modification and expression changes in genes associated with H₂S toxicity and detoxification. Our results demonstrate that the modification of highly conserved physiological pathways associated with essential mitochondrial processes mediates tolerance to physiochemical stress. In addition, the same pathways, genes, and—in some instances—codons are implicated in H₂S adaptation in lineages that span 40 million years of evolution.

ABSTRACT Chlamydia trachomatis is a significant pathogen with global and economic impact. As an obligate intracellular pathogen, C. trachomatis resides inside the inclusion, a parasitophorous vacuole, and depends on the host cell for survival and transition through a biphasic development cycle. During infection, C. trachomatis is known to manipulate multiple signaling pathways and recruit an assortment of host proteins to the inclusion membrane, including host kinases. Here, we show recruitment of multiple isoforms of protein kinase C (PKC) including active phosphorylated PKC isoforms to the chlamydial inclusion colocalizing with active Src family kinases. Pharmacological inhibition of PKC led to a modest reduction of infectious progeny production. PKC phosphorylated substrates were seen recruited to the entire periphery of the inclusion membrane. Infected whole cell lysates showed altered PKC phosphorylation of substrates during the course of infection. Assessment of different chlamydial species showed recruitment of PKC and PKC phosphorylated substrates were limited to C. trachomatis. Taken together, PKC and PKC substrate recruitment may provide significant insights into how C. trachomatis manipulates multiple host signaling cascades during infection. Chlamydia trachomatis is an obligate intracellular pathogen that uses host proteins such as protein kinase C for intracellular survival.

is the leading cause of bacterial sexually transmitted infections (STIs) and preventable blindness. Untreated, asymptomatic infection as well as frequent re-infection are common and may drive pelvic inflammatory disease, ectopic pregnancy, and infertility. models of chlamydial infection continue to be instrumental in progress toward a vaccine and further elucidating the pathogenesis of this intracellular bacterium, however significant gaps in our understanding remain. Chlamydial host cell exit occurs via two mechanisms, lysis and extrusion, although the latter has yet to be reported and its biological role is unclear. The objective of this study was to investigate whether chlamydial extrusions are shed following infection with multiple strains of . We utilized an established C3H/HeJ murine cervicovaginal infection model with serovars D and L2 and the strain MoPn to monitor the (i) time course of infection and mode of host cell exit, (ii) mucosal and systemic immune response to infection, and (iii) gross and histopathology following clearance of active infection. The key finding herein is the first identification of chlamydial extrusions shed from host cells in an model. Extrusions, a recently appreciated mode of host cell exit and potential means of dissemination, had been previously observed solely . The results of this study demonstrate that chlamydial extrusions exist and thus warrant further investigation to determine their role in chlamydial pathogenesis.

Chlamydia trachomatis is an obligate intracellular pathogen with global health and economic impact. Upon infection, C. trachomatis resides within a protective niche, the inclusion, wherein it replicates and usurps host cell machinery and resources. The inclusion membrane is the key host-pathogen interface that governs specific protein-protein interactions to manipulate host signaling pathways. At the conclusion of the infection cycle, C. trachomatis exits the host cell via lysis or extrusion. Extrusion depends on the phosphorylation state of myosin light chain 2 (MLC2); the extent of phosphorylation is determined by the ongoing opposing activities of myosin phosphatase (MYPT1) and myosin kinase (MLCK). Previously, it was shown that MYPT1 is recruited to the inclusion and interacts with CT228 for regulation of host cell egress. In this study, we generated a targeted chromosomal mutation of CT228 (L2-ΔCT228) using the TargeTron system and demonstrate a loss of MYPT1 recruitment and increase in extrusion production in vitro. Mutation of CT228 did not affect chlamydial growth in cell culture or recruitment of MLC2. Moreover, we document a delay in clearance of L2-ΔCT228 during murine intravaginal infection as well as a reduction in systemic humoral response, relative to L2-wild type. Taken together, the data suggest that loss of MYPT1 recruitment (as a result of CT228 disruption) regulates the degree of host cell exit via extrusion and affects the longevity of infection in vivo.

Extreme environments test the limits of life. Still, some organisms thrive in harsh conditions, begging the question whether the repeated colonization of extreme environments is facilitated by predictable and repeatable evolutionary innovations. We identified the mechanistic basis underlying convergent evolution of tolerance to hydrogen sulfide (H2S) - a potent toxicant that impairs mitochondrial function - across evolutionarily independent lineages of a fish (Poecilia mexicana, Poeciliidae) from H2S-rich freshwater springs. We found that mitochondrial function is maintained in the presence of H2S in sulfide spring P. mexicana, but not ancestral lineages in adjacent nonsulfidic habitats, due to convergent adaptations in both the primary toxicity target and a major detoxification enzyme. Additionally, we show that H2S tolerance in 10 independent lineages of sulfide spring fishes across multiple genera of Poeciliidae is mediated by convergent modification and expression changes of genes associated with H2S toxicity and detoxification. Our results demonstrate that the repeated modification of highly conserved physiological pathways associated with essential mitochondrial processes enabled the colonization of novel environments. Footnotes * https://github.com/michitobler/convergent_h2s_evolution

Of over 7000 patients referred to a diagnostic laboratory, 28% had diagnoses based on DNA sequencing, 5% of whom had two or more diagnoses. Their phenotypes could be better understood by considering whether the implicated genes affect independent biologic processes or organ systems. Medical genetics focuses on the relationship between observed phenotypes and their underlying genotypes, modes of transmission, and risks of recurrence. Expected patterns of mendelian inheritance are often used to confirm the identification of disease genes, and deviations from mendelian expectations have led to the discovery of more complicated genetic underpinnings of disease (Fig. S1 in the Supplementary Appendix, available with the full text of this article at NEJM.org). 1 – 8 Multiple (or dual) molecular diagnoses involve more than one clinical diagnosis and more than one genetic locus (Figure 1), each segregating independently. Diagnostic whole-exome sequencing affords opportunities for providing insights into relationships . . .