Effects of Hypoxia on the Eye in Patients with Obstructive Sleep Apnea Syndrome

Objective: Hypoxia, perfusion pressure changes, systemic hypertension, vasospasm, increase in blood viscosity and small vessels' resistance may cause ischemia in Obstructive sleep apnea syndrome (OSAS). The aim of this study is to assess the effect of hypoxia on the eye (choroidal and corneal thicknesses) in patients with OSAS

Involvement of autophagy in T cell biology

Autophagy is an essential cellular pathway that sequesters various cytoplasmic components, including accumulated proteins, damaged organelles or invading microorganisms and delivers them to lysosomes for degradation. The function of autophagy has been reported in various tissues and systems, including its role in the regulation of cellular immunity. Autophagy plays a fundamental role at various stages of T cell maturation. It regulates the thymocyte selection and the generation of T cell repertoire by presenting intracellular antigens to MHC class molecules. Autophagy is crucial for metabolic regulation of T cells, and therefore supports cell survival and homeostasis, particularly in activated mature T cells. Furthermore, deletion of specific autophagy-related genes induces several immunological alterations including differentiation of activated T cells into regulatory, memory or natural killer T cells. In this review, we emphasize the impact of autophagy on T cell development, activation and differentiation, which is pivotal for the adaptive immune system

Identification of a serine-threonine kinase as a novel autophagic regulator

Phospholipid dependent Serine/Threonine kinases are shown to be involved in cellular mechanisms and disease related pathways. Upon different intracellular stimuli, these kinases are activated and functions. Several chemical analogues such as Phorbol 12-Mystrate 13-Acetate (PMA) and Ceramide were synthesized to mimic intracellular stimuli to study function of these kinases. For several of these kinases, activation is dependent on both PMA and a Calcium ionophore such as ionomycin. Strikingly, deregulation of these kinases has been identified in several cancers. Recent studies showed that autophagy, which evolutionary conserved cellular degradation mechanism to maintain homeostasis, is also involved in carcinogenesis. According to literature, there are no robust studies to show the interaction between autophagy and serine threonine kinases. Thus, in our study we focused to identify a novel Ser/Thr kinases involved in regulation of autophagy in cancer

PMA functions as an autophagy inhibitor through activation of a serine threonine kinase

Serine-threonine kinases have vital roles in various signalling pathways such as proliferation, differentiation and apoptosis. Thus, they served as crucial players in health and disease including cancer. Isozymes of these families show tissue specific expression patterns and function specifically in different pathways. Autophagy is another major process in the cell which degrades long-lived, non-functional organelles and proteins to sustain the homeostasis. Moreover, as well as serine threonine kinases, autophagy was also found to relate with cancer in different stages. To date, relationship between serine-threonine protein kinases and autophagy has not been well studied. Therefore, we utilized PMA which is one of the three different activatory signals of this kinase family to activate the certain subgroup and we studied the role of these kinases on autophagy regulation

Evaluation of the vestibular system with video head impulse test in pregnant women with hyperemesis gravidarum

Ozgu-Erdinc, A. Seval/0000-0002-6132-5779WOS:000561045200001PubMed: 32820578Aim We aimed to evaluate the semicircular canal functions of the vestibular system in pregnant women with hyperemesis gravidarum. Methods This is a prospective case-control study. Among pregnant women in their first trimester (<14. gestational weeks) who presented to our outpatient clinic, 36 patients diagnosed with hyperemesis gravidarum defined as persistent nausea and vomiting requiring intravenous hydration or loss of at least 5% of prepregnancy weight and 34 healthy pregnant without nausea and vomiting were included. Otorhinolaryngologic examination and video head impulse test (vHIT) was performed to all patients. Vestibular-ocular reflex (VOR) gain and gain asymmetry were assessed between groups. Results The VOR gains in each semicircular canal did not differ between hyperemesis and control groups. Using a VOR gain cut-off value of 0.8, the groups were compared in terms of the frequency of low values. In the hyperemesis group, abnormally low gain values of left anterior canal were more frequently observed than in the control group (32 [88.9%], 22 [64.7%], respectively,P= 0.01). In left anterior-right posterior (LARP) plane VOR gain asymmetry was higher in hyperemesis group (13.5 [1.0-71.0], 6.0 [0.0-35.0],P= 0.001). No significant gain asymmetry was detected between the groups in the other planes. Conclusion Semicircular canal functions were not abnormal globally in women with hyperemesis gravidarum. However, higher LARP plane asymmetry and low LA gain in women with hyperemesis suggests need for further research to clarify functional role of vestibular system on hyperemesis gravidarum

Considerations for the selection of tests for SARS-CoV-2 molecular diagnostics

During the course of 2020, the outbreak of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) spread rapidly across the world. Clinical diagnostic testing for SARS-Cov-2 infection has relied on the real-time Reverse Transcriptase Polymerase Chain Reaction and is considered the gold standard assay. Commercial vendors and laboratories quickly mobilised to develop diagnostic tests to detect the novel coronavirus, which was fundamentally important in the pandemic response. These SARS-Cov-2 assays were developed in line with the Food Drug Administration-Emergency Use Authorization guidance. Although new tests are continuously being developed, information about SARS-CoV-2 diagnostic molecular test accuracy has been limited and at times controversial. Therefore, the analytical and clinical performance of SARS-CoV-2 test kits should be carefully considered by the appropriate regulatory authorities and evaluated by independent laboratory validation. This would provide improved end-user confidence in selecting the most reliable and accurate diagnostic test. Moreover, it is unclear whether some of these rapidly developed tests have been subjected to rigorous quality control and assurance required under good manufacturing practice. Variable target gene regions selected for currently available tests, potential mutation in target gene regions, non-standardized pre-analytic phase, a lack of manufacturer independent validation data all create difficulties in selecting tests appropriate for different countries and laboratories. Here we provide information on test criteria which are important in the assessment and selection of SARS-CoV-2 molecular diagnostic tests and outline the potential issues associated with a proportion of the tests on the market

The ZEB2-dependent EMT transcriptional programme drives therapy resistance by activating nucleotide excision repair genes ERCC1 and ERCC4 in colorectal cancer

Resistance to adjuvant chemotherapy is a major clinical problem in the treatment of colorectal cancer (CRC). The aim of this study was to elucidate the role of an epithelial to mesenchymal transition (EMT)-inducing protein, ZEB2, in chemoresistance of CRC, and to uncover the underlying mechanism. We performed IHC for ZEB2 and association analyses with clinical outcomes on primary CRC and matched CRC liver metastases in compliance with observational biomarker study guidelines. ZEB2 expression in primary tumours was an independent prognostic marker of reduced overall survival and disease-free survival in patients who received adjuvant FOLFOX chemotherapy. ZEB2 expression was retained in 96% of liver metastases. The ZEB2-dependent EMT transcriptional programme activated nucleotide excision repair (NER) pathway largely via upregulation of the ERCC1 gene and other components in NER pathway, leading to enhanced viability of CRC cells upon oxaliplatin treatment. ERCC1-overexpressing CRC cells did not respond to oxaliplatin in vivo, as assessed using a murine orthotopic model in a randomised and blinded preclinical study. Our findings show that ZEB2 is a biomarker of tumour response to chemotherapy and risk of recurrence in CRC patients. We propose that the ZEB2-ERCC1 axis is a key determinant of chemoresistance in CRC.</p