Environment Impacts the Metabolic Dependencies of Ras-Driven Non-Small Cell Lung Cancer

Cultured cells convert glucose to lactate, and glutamine is the major source of tricarboxylic acid (TCA)-cycle carbon, but whether the same metabolic phenotype is found in tumors is less studied. We infused mice with lung cancers with isotope-labeled glucose or glutamine and compared the fate of these nutrients in tumor and normal tissue. As expected, lung tumors exhibit increased lactate production from glucose. However, glutamine utilization by both lung tumors and normal lung was minimal, with lung tumors showing increased glucose contribution to the TCA cycle relative to normal lung tissue. Deletion of enzymes involved in glucose oxidation demonstrates that glucose carbon contribution to the TCA cycle is required for tumor formation. These data suggest that understanding nutrient utilization by tumors can predict metabolic dependencies of cancers in vivo. Furthermore, these data argue that the in vivo environment is an important determinant of the metabolic phenotype of cancer cells.National Science Foundation (U.S.) (Grant T32GM007287

Tracheostomal Myiasis: A Case Report and Review of the Literature

“Myiasis” is considered in Hindu mythology as “God's punishment for sinners.” It is known to infest live human or animal tissue. Literature abounds with reports of myiasis affecting the nasal cavity, ear, nonhealing ulcers, exophytic malignant growth, and cutaneous tissue. But report of myiasis of the tracheal stoma is rare. Only a few cases of tracheal myiasis have been reported in literature. We report a case of tracheostomal myiasis in an elderly male. The species which had infested the stoma was identified as Chrysomya bezziana, an obligate parasite. This is to our knowledge the first case report of an obligate parasite (Chrysomya bezziana) infestation of the tracheostoma from India

Numerical Simulation of Asymmetrically Altered Growth as Initiation Mechanism of Scoliosis

The causes of idiopathic scoliosis are still uncertain; buckling is mentioned often, but never proven. The authors hypothesize another option: unilateral postponement of growth of MM Rotatores or of ligamentum flavum and intertransverse ligament. In this paper, both buckling and the two new theories of scoliotic initiation are studied using a new finite element model that simulates the mechanical behavior of the human spine. This model was validated by the stiffness data of Panjabi et al. (J. Biomech. 9:185–192, 1976). After a small correction of the prestrain of some ligaments and the MM Rotatores the model appeared to be valid. The postponement in growth was translated in the numerical model in an asymmetrical stiffness. The spine was loaded axially and the resulting deformation was analyzed for the presence of the coupling of lateral deviation and axial rotation that is characteristic for scoliosis. Only unilateral postponement of growth of ligamentum flavum and intertransverse ligament appeared to initiate scoliosis. Buckling did not initiate scoliosis

Cancer cell plasticity: from cellular, molecular, and genetic mechanisms to tumor heterogeneity and drug resistance

Cancer is a complex disease displaying a variety of cell states and phenotypes. This diversity, known as cancer cell plasticity, confers cancer cells the ability to change in response to their environment, leading to increased tumor diversity and drug resistance. This review explores the intricate landscape of cancer cell plasticity, offering a deep dive into the cellular, molecular, and genetic mechanisms that underlie this phenomenon. Cancer cell plasticity is intertwined with processes such as epithelial-mesenchymal transition and the acquisition of stem cell-like features. These processes are pivotal in the development and progression of tumors, contributing to the multifaceted nature of cancer and the challenges associated with its treatment. Despite significant advancements in targeted therapies, cancer cell adaptability and subsequent therapy-induced resistance remain persistent obstacles in achieving consistent, successful cancer treatment outcomes. Our review delves into the array of mechanisms cancer cells exploit to maintain plasticity, including epigenetic modifications, alterations in signaling pathways, and environmental interactions. We discuss strategies to counteract cancer cell plasticity, such as targeting specific cellular pathways and employing combination therapies. These strategies promise to enhance the efficacy of cancer treatments and mitigate therapy resistance. In conclusion, this review offers a holistic, detailed exploration of cancer cell plasticity, aiming to bolster the understanding and approach toward tackling the challenges posed by tumor heterogeneity and drug resistance. As articulated in this review, the delineation of cellular, molecular, and genetic mechanisms underlying tumor heterogeneity and drug resistance seeks to contribute substantially to the progress in cancer therapeutics and the advancement of precision medicine, ultimately enhancing the prospects for effective cancer treatment and patient outcomes.Open Access funding provided by the Qatar National Library. This study was funded by Sidra Medicine Research Fund to Ajaz A. Bhat (SDR400105) and Ammira S. Al-Shabeeb Akil (SDR400175).Scopu

Clinical and biological heterogeneity of multisystem inflammatory syndrome in adults following SARS-CoV-2 infection: a case series

ImportanceMultisystem inflammatory syndrome in adults (MIS-A) is a poorly understood complication of SARS-CoV-2 infection with significant morbidity and mortality.ObjectiveIdentify clinical, immunological, and histopathologic features of MIS-A to improve understanding of the pathophysiology and approach to treatment.DesignThree cases of MIS-A following SARS-CoV-2 infection were clinically identified between October 2021 – March 2022 using the U.S. Centers for Disease Control and Prevention diagnostic criteria. Clinical, laboratory, imaging, and tissue data were assessed.FindingsAll three patients developed acute onset cardiogenic shock and demonstrated elevated inflammatory biomarkers at the time of hospital admission that resolved over time. One case co-occurred with new onset Type 1 diabetes and sepsis. Retrospective analysis of myocardial tissue from one case identified SARS-CoV-2 RNA. All three patients fully recovered with standard of care interventions plus immunomodulatory therapy that included intravenous immunoglobulin, corticosteroids, and in two cases, anakinra.ConclusionMIS-A is a severe post-acute sequela of COVID-19 characterized by systemic elevation of inflammatory biomarkers. In this series of three cases, we find that although clinical courses and co-existent diseases vary, even severe presentations have potential for full recovery with prompt recognition and treatment. In addition to cardiogenic shock, glucose intolerance, unmasking of autoimmune disease, and sepsis can be features of MIS-A, and SARS-CoV-2 myocarditis can lead to a similar clinical syndrome

Quality of life after gender reassignment surgery in transwomen

Background: Gender dysphoria is a condition in which there is discrepancy between a person's gender identity and that person's sex assigned at birth. Gender reassignment surgery (GRS) has an important role in alleviating the distress caused by gender dysphoria and it is medically necessary. The literature on quality of life (QoL) of transgenders post-GRS is limited in India.Methods: This is a prospective study on transgender women who volunteered to undergo male to female (MtF) GRS from March 2015 to August 2017. The demographic details and the surgical complications were registered. The Quality of life using the WHOQOL-BREF questionnaire was measured both before and a year after the surgery. The data were compared and presented.Results: A total of 62 GRS were performed during the study period. In that, 43 patients are literate (69.35%) and only 31.93% are employed in a socially respectable position. Our study shows significant improvement in physical, psychological and social health domains after the Surgery. Highest improvement was observed in the psychological health domain. There were no major complications observed in our study group.Conclusions: The surgical management improved the QOL in the first three domains of WHOQOL-BREF instrument namely physical health, psychological health and social relationship. Among these three domains, there is a significant improvement in psychological health. Hence, GRS has an important role in relieving the psychological distress caused by gender dysphoria and significantly improves the quality of life postoperatively.</jats:p