Immune cell dysregulation and lymphopenia characterize COVID-19 pathology in moderate to severe disease. While underlying inflammatory factors have been extensively studied, homeostatic and mucosal migratory signatures remain largely unexplored as causative factors. In this study we evaluated the association of circulating IL-6, soluble mucosal addressin cell adhesion molecule (sMAdCAM) and IL-15 with cellular dysfunction characterizing mild and hypoxemic stages of COVID-19. A cohort of SARS-CoV-2 infected individuals (n=125) at various stages of disease progression together with healthy controls (n=16) were recruited from COVID Care Centres (CCCs) across Mumbai, India. Multiparametric flow cytometry was used to perform in-depth immune subset characterization and to measure plasma IL-6 levels. sMAdCAM, IL-15 levels were quantified using ELISA. Distinct depletion profiles, with relative sparing of CD8 effector memory and CD4+ regulatory T cells was observed in hypoxemic disease within the lymphocyte compartment. An apparent increase in the frequency of intermediate monocytes characterized both mild as well as hypoxemic disease. IL-6 levels inversely correlated with those of sMAdCAM and both markers showed converse associations with observed lympho-depletion suggesting opposing roles in pathogenesis. Interestingly, IL-15, a key cytokine involved in lymphocyte activation and homeostasis, was detected in symptomatic individuals but not in healthy controls or asymptomatic cases. Further, negative association of plasma IL-15 with depleted T, B and NK subsets suggested a compensatory production of this cytokine in response to the profound lymphopenia. Finally, higher levels of plasma IL-15 and IL-6, but not sMAdCAM, were associated with longer duration of hospitalization.

Undifferentiated pleomorphic sarcoma (UPS) and malignant peripheral nerve sheath tumor (MPNST) are aggressive soft tissue sarcomas that do not respond well to current treatment modalities. The limited availability of UPS and MPNST cell lines makes it challenging to identify potential therapeutic targets in a laboratory setting. Understanding the urgent need for improved treatments for these tumors and the limited cellular models led us to generate additional cell lines to study these rare cancers further. Patient-derived tumors were used to establish 5 new UPS models, including one radiation-associated UPS: UPS060.1, UPS271.1, UPS511, UPS0103, and RIS620; and 3 new models of MPNST: MPNST007, MPNST3813E, and MPNST4970. This study examined the utility of the new cell lines as sarcoma models by assessing tumorigenic potential and mutation status for known sarcoma-related genes. All the cell lines formed colonies and migrated in vitro. The in vivo tumorigenic potential of each cell line was determined by either subcutaneous injection of cells or implantation of tumor tissue into immunocompromised mice. UPS060.1, UPS271.1, and UPS511 cells formed tumors in mice upon subcutaneous injection. UPS0103 and RIS620 tumor implants formed tumors in vivo, as did MPNST007 and MPNST3813E tumor implants. Mutation analysis of a panel of genes frequently mutated in sarcomas showed that two of the three MPNST cell lines had NF1 mutations. Two of the three MPNST cell lines had mutations in polycomb repressive complex 2 members. These new cellular models provide the scientific community with powerful tools for detailed studies of sarcomagenesis and investigate novel therapies for UPS and MPNST.

Abstract-Use of unclaimed or donated bodies for education & research in anatomical sciences have been recognized as valuable means of cadaver by the Anatomical professionals but adequate and continuous availability of cadaver has been one of the major concerns of the stakeholders of health science institutions and biomedical research organisations in order to fulfil objectives of anatomy curriculum of the graduate, postgraduate and specialist training & research programmes in medical sciences. Deficiency of cadaver for dissection and research in medical institutions has been further deteriorated in present scenario attributed to steep increase in number of medical, dental and other health science institutions during last decade. The present paper analysed the existing sources of cadavers associated with challenges in process of procurement by the medical colleges and other health science institutions to identify the issues needs to be addressed immediately in order to ensure sustained solutions of these challenges and augment adequate cadavers supply to meet rapid rate of advancement in surgical techniques, altered pattern of structural shape, size and histology. An attempt has also been made to suggest possible sustainable solution for promoting voluntary whole body donation as well as corrective measures for optimum utilisation of unclaimed body in acceptable form from government sources for learning & research in anatomical sciences.

24Growth hormone (GH) had direct effects on the glomerular podocyte. Increased levels of GH 25 are implicated in the pathogenesis of renal abnormalities in acromegaly and in diabetic 26 nephropathy in Type 1 diabetes mellitus. We investigated the role of Transforming growth 27 factor-β1 (TGF-β1) in GH's effects on the glomerular podocyte. Exposure of podocytes to GH 28 resulted in elevated expression of TGF-β1 and was concurrent with increased phosphorylation 29 of SMAD2/3 and nuclear accumulation of SMAD4. Conditioned media from podocytes exposed 30 to GH also triggered SMAD signaling. Podocytes treated with GH showed increased 31 permeability to albumin. Mice injected with GH demonstrated increased kidney size, glomerular 32 hypertrophy, and proteinuria. The renal manifestations in GH injected mice were associated with 33 increased TGF-β1 expression and activation of TGF-β1 signaling pathways. Concurrent 34 administration of TGF-β receptor antagonist (SB431542) with GH abrogated these renal effects 35 of GH administration. These results reveal the role of TGF-β1 in GH's actions on the glomerular 36 podocyte and provide a novel mechanistic basis for GH-induced glomerular dysfunction in 37 clinical conditions such as diabetes and acromegaly. 38 39 40 41 42 43

Представлены сведения о редком наследственном заболевании-первичной гипертрофической остеоартропатии с аутосомно-доминантным и аутосомно-рецессивным наследованием. Генетическая гетерогенность обусловливает клинический полиморфизм симптомов, появляющихся в детском и подростковом возрасте. Дифференциальную диагностику необходимо проводить со вторичной гипертрофической остеоартропатией, встречающейся в 90% случаев и ассоциированной со злокачественными новообразованиями, ревматическими болезнями и другими заболеваниями. Важное значение отводится рентгенологическим признакам, позволяющим уточнить локализацию, протяженность и характер поражения костей. Специфическое лечение заболевания отсутствует. Ключевые слова: гипертрофическая остеоартропатия, первичная, вторичная, диагностика, дифференциальная диагностика Для цитирования: Трисветова ЕЛ. Первичная гипертрофическая остеоартропатия. Научно-практическая ревматология 2020;58(5):544-549.