Alterations in RNA editing in skeletal muscle following exercise training in individuals with Parkinson's disease.

Parkinson's Disease (PD) is the second most common neurodegenerative disease behind Alzheimer's Disease, currently affecting more than 10 million people worldwide and 1.5 times more males than females. The progression of PD results in the loss of function due to neurodegeneration and neuroinflammation. The etiology of PD is multifactorial, including both genetic and environmental origins. Here we explored changes in RNA editing, specifically editing through the actions of the Adenosine Deaminases Acting on RNA (ADARs), in the progression of PD. Analysis of ADAR editing of skeletal muscle transcriptomes from PD patients and controls, including those that engaged in a rehabilitative exercise training program revealed significant differences in ADAR editing patterns based on age, disease status, and following rehabilitative exercise. Further, deleterious editing events in protein coding regions were identified in multiple genes with known associations to PD pathogenesis. Our findings of differential ADAR editing complement findings of changes in transcriptional networks identified by a recent study and offer insights into dynamic ADAR editing changes associated with PD pathogenesis.

Comparison of Efficacy of Vaginal Misoprostol versus a Synthetic Osmotic Dilator (Dilapan-S) for Cervical Preparation before Operative Hysteroscopy: A Randomized Controlled Study.

Objectives: To compare the need for mechanical cervical dilatation following vaginal misoprostol or synthetic osmotic dilator (Dilapan-S) usage for cervical preparation before operative hysteroscopy. Materials and Methods: Fifty-five premenopausal women scheduled for operative hysteroscopic procedures with a 26 Fr resectoscope were included in this randomized, controlled clinical trial. After randomization, either 400 µg of vaginal misoprostol or intracervical synthetic osmotic dilator (Dilapan-S) was inserted 12 h before operative hysteroscopy. The need for additional mechanical cervical dilatation before insertion of the resectoscope was compared between the two groups. Initial cervical diameter before mechanical dilatation, intraoperative complications (cervical tears, creation of a false passage), and ease of dilatation were also compared between the two groups. Results: In the misoprostol group, 92% of women required additional mechanical cervical dilatation, whereas only 36% of women in the Dilapan-S group required additional dilatation (P < 0.05). The median initial cervical diameter achieved with Dilapan was 9 mm (Q1: 7 mm; Q3: 10 mm), and with misoprostol, it was 6 mm (Q1: 4.5 mm; Q3: 8 mm) (P < 0.05). There was no significant difference in other outcome parameters between the two groups. Conclusion: Synthetic osmotic dilator (Dilapan-S) is more efficacious than vaginal misoprostol at ripening the cervix before operative hysteroscopy.

Comparison of Fasting Insulin Level, Homeostatic Model of Insulin Resistance, and Lipid Levels between Patients with Primary Hypertension and Normotensive Subjects.

BACKGROUND: Hyperinsulinemia and insulin resistance occurs in obese patients with primary hypertension independent of diabetes and obesity. This study was aimed at assessing serum fasting insulin levels, the homeostatic model assessment for insulin resistance (HOMA-IR), and serum lipid levels in non-obese patients with primary hypertension when compared to normotensive subjects. METHODS: This observational study comprised 100 patients over 18 years of age, divided into two groups. The hypertensive group comprised non-obese patients with primary hypertension (n=50); the normotensive group comprised normotensive age- and sex-matched individuals (n=50). Patients with diabetes, impaired fasting glucose, obesity, and other causative factors of insulin resistance were excluded from the study. Serum fasting insulin levels and fasting lipid profiles were measured, and insulin resistance was calculated using HOMA-IR. These data were compared between the two groups. Pearson's correlation coefficient was used to assess the extent of a linear relationship between HOMA-IR and to evaluate the association between HOMA-IR and systolic and diastolic blood pressures. RESULTS: Mean serum fasting insulin levels (mIU/L), mean HOMA-IR values, and fasting triglyceride levels (mg/dL) were significantly higher in the hypertensive versus normotensive patients (10.32 versus 6.46, P<0.001; 1.35 versus 0.84, P<0.001; 113.70 versus 97.04, P=0.005, respectively). The HOMA-IR levels were associated with systolic blood pressure (r value 0.764, P=0.0005). CONCLUSION: We observed significantly higher fasting insulin levels, serum triglyceride levels, and HOMA-IR reflecting hyperinsulinemia and possibly an insulin-resistant state among primary hypertension patients with no other causally linked factors for insulin resistance. We observed a significant correlation between systolic blood pressure and HOMA-IR.

Role of secondary sepsis in COVID-19 mortality: Observations on patients with preexisting diabetes mellitus and newly diagnosed hyperglycemia.

Diabetics who develop severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) are more likely to have severe disease, higher odds of intensive care requirement and mortality. Fifteen percent of patients have new onset hyperglycemia. We studied the comparative outcomes between prior DM, newly detected hyperglycemia and assessed role of secondary sepsis on mortality. RWe performed a r etrospective study of confirmed SARS-CoV-2 patients at a tertiary care hospital in Chennai, India. Patients were divided as 2 groups (Group 1: With preexisting diabetes mellitus, Group 2: With newly diagnosed hyperglycemia due to newly detected diabetes mellitus or non-diabetic hyperglycemia. Clinical and laboratory data was analysed. Two hundred and thirty eight patients had prior-diabetes mellitus (Group 1) and 40 had newly diagnosed hyperglycemia (Group 2). Thirty four of group 1 and 7 of group 2 patients required intensive care. Mean capillary blood glucose (MCBG) during hospital stay was 207 mg/dl (Group 1) and 192 mg/dl (Group 2). Twentysix patients (9.3%) had secondary sepsis of which sixteen died. Logistic regression identified secondary sepsis(p<0.0001), elevated D-dimer >6 fold (p= 0.0001), elderly p=0.0045), male (p=0.0006), NLR >5 (p=0.01),serum creatinine ≥2 mg/dl (p=0.0004), FiO2 requirement >0.6 in first 48 hours (p=0.001) as mortality predictors.Our study observed a 14.38 % prevalence of newly diagnosed DM or non-diabetic hyperglycemia. Secondary sepsis and >6 fold elevation in D-dimer were strong predictors of mortality. Steroid use possibly contributed to secondary sepsis. Early identification and aggressive management of secondary sepsis are necessary for diabetics.

Common mental disorders among women and its social correlates in an urban marginalized populace in South India.

BACKGROUND: Common mental disorders (CMD) cause a range of health, social and economic burden, and disorders like depression and anxiety are more prevalent among women. Prevalence and factors contributing to increased vulnerability for CMDs have regional variation. Identification of factors contributing to the vulnerability is essential to both psychiatric epidemiology and in addressing mental health challenges in the community. METHODS: This cross-sectional study aimed at understanding the burden of CMD and its association with social determinants of mental health. Women hailing from urban slum attending the outpatient family care facility for their medical problems constituted the sample. Data was collected using a clinical research form with variables such as sociodemographic profile, health profile, and psychosocial profile. The questionnaire had specific questions on indicators of poverty, certain stressors, and support system. Presence of CMD was assessed using Clinical Interview Schedule-Revised (CIS-R), a standard tool for CMD research in primary care settings. A cut off score of 12 and above was considered for detecting CMD. Research ethical principles were adhered to and data was analyzed using SPSS 21.0. RESULTS: Among 172 women, 77 (44.8%) were diagnosed to have CMDs. Univariate analysis revealed a significant association between age, marital status, living arrangement, educational level, difficulty with buying food, presence of debt, chronic medical illness, husband's alcohol use, marital satisfaction, experiencing abuse, family support, religious participation, and a diagnosis of CMD. Multivariate analysis showed high burden with nuclear family arrangement, difficulty to buy food, experiencing abuse and, low burden with higher educational level, family support, and religious participation. CONCLUSION: Considering the high prevalence and the treatment gap of CMDs in primary setting, family-physician should be sensitized for detection and management of CMDs. Social interventions targeting poverty, women's education and empowerment, and support system are likely to decrease the burden of CMDs in this population.

Rare Presentation of Isolated Spontaneous Bacterial Empyema without Concomitant Ascites in a Patient with Cirrhosis.

In decompensated cirrhosis, massive ascites and pleural effusion (hepatic hydrothorax) can be complicated by infection, which manifests either as spontaneous bacterial peritonitis (SBP) or spontaneous bacterial empyema (SBE). SBE is a distinct and often underdiagnosed complication having different pathogenesis and treatment strategy when compared with parapneumonic empyema. Hepatic hydrothorax in the absence of ascites is rare in patients with cirrhosis. The occurrence of SBE without SBP or ascites is even more of a rarity in cirrhosis and carries great morbidity and mortality. Here we report a case of an elderly female patient with cirrhosis (Child-Pugh Class B) who had unusual features of isolated right-sided hepatic hydrothorax without clinically evident ascites and was later diagnosed as having SBE based on imaging of the thorax, pleural fluid analysis, and cultures. The patient was initially treated conservatively with antibiotics, and diuretics, and later pigtail insertion and drainage was done.

Course of COVID-19 Based on Admission D-Dimer Levels and Its Influence on Thrombosis and Mortality.

BACKGROUND: Arterial and venous thrombosis is one of the major complications of coronavirus disease 2019 (COVID-19) infection. Studies have not assessed the difference in D-dimer levels between patients who develop thrombosis and those who do not. METHODS: Our study retrospectively assessed D-dimer levels in all virus confirmed hospitalized patients between May to September, 2020. Patients were divided into three groups: group 1 with normal D-dimer of < 0.5 µg/mL, group 2 with elevation up to six folds, and group 3 with more than six-fold elevation. Statistical analysis was done using SPSS software 23.0. RESULTS: Seven hundred twenty patients (group1 (n = 414), group 2 (n = 284) and group 3 (n = 22)) were studied. Eight thrombotic events were observed. Events were two with stroke, two non-ST elevation myocardial infarction and one each of ST elevation myocardial infarction, superior mesenteric artery thrombosis with bowel gangrene, arteriovenous fistula thrombus and unstable angina. No significant difference (P = 0.11) was observed between median D-dimer levels among patients who developed thrombosis (1.34) and those who did not develop thrombosis (0.91). Twenty-nine patients died. The adjusted odds of death among those with a six-fold or higher elevation in D-dimer was 128.4 (95% confidence interval (CI): 14.2 - 446.3, P < 0.001), while adjusted odds of developing clinical thrombosis was 1.96 (95% CI: 0.82 - 18.2, P = 0.18). CONCLUSIONS: Our study observed a 1.1% in-hospital incidence of clinical thrombosis. While, a six-fold elevation in D-dimer was significantly associated with death; the same was not a strong predictor of thrombosis; an observation which implies that dose of anticoagulation should not be based on absolute D-dimer level.

Transcriptional response of key metabolic and stress response genes of a nuculanid bivalve, Lembulus bicuspidatus from an oxygen minimum zone exposed to hypoxia-reoxygenation.

Benthic animals inhabiting the edges of marine oxygen minimum zones (OMZ) are exposed to unpredictable large fluctuations of oxygen levels. Sessile organisms including bivalves must depend on physiological adaptations to withstand these conditions. However, as habitats are rather inaccessible, physiological adaptations of the OMZ margin inhabitants to oxygen fluctuations are not well understood. We therefore investigated the transcriptional responses of selected key genes involved in energy metabolism and stress protection in a dominant benthic species of the northern edge of the Namibian OMZ, the nuculanid clam Lembulus bicuspidatus,. We exposed clams to normoxia (~5.8 ml O2 l-1), severe hypoxia (36 h at ~0.01 ml O2 l-1) and post-hypoxic recovery (24 h of normoxia following 36 h of severe hypoxia). Using newly identified gene sequences, we determined the transcriptional responses to hypoxia and reoxygenation of the mitochondrial aerobic energy metabolism (pyruvate dehydrogenase E1 complex, cytochrome c oxidase, citrate synthase, and adenine nucleotide translocator), anaerobic glycolysis (hexokinase (HK), phosphoenolpyruvate carboxykinase (PEPCK), phosphofructokinase, and aldolase), mitochondrial antioxidants (glutaredoxin, peroxiredoxin, and uncoupling protein UCP2) and stress protection mechanisms (a molecular chaperone HSP70 and a mitochondrial quality control protein MIEAP) in the gills and the labial palps of L. bicuspidatus. Exposure to severe hypoxia transcriptionally stimulated anaerobic glycolysis (including HK and PEPCK), antioxidant protection (UCP2), and quality control mechanisms (HSP70 and MIEAP) in the gills of L. bicuspidatus. Unlike UCP2, mRNA levels of the thiol-dependent mitochondrial antioxidants were not affected by hypoxia-reoxygenation stress. Transcript levels of marker genes for aerobic energy metabolism were not responsive to oxygen fluctuations in L. bicuspidatus. Our findings highlight the probable importance of anaerobic succinate production (via PEPCK) and mitochondrial and proteome quality control mechanisms in responses to oxygen fluctuations of the OMZ bivalve L.bicuspidatus. The reaction of L.bicuspidatus to oxygen fluctuations implies parallels to that of other hypoxia-tolerant bivalves, such as intertidal species.

Clinical Features of Four West Nile Virus Cases and Its Molecular Characterization from a South Indian Tertiary Care Hospital.

West Nile virus (WNV) is currently a significant reemerging virus of the 21st century. It belongs to the family Flaviviridae and genus Flavivirus. Although it is primarily transmitted by the Culex spp of mosquitoes, other routes of transmission are also well defined. Of eight lineages described, Lineage 1a has been reported from many parts of South India and is known to cause neuroinvasive illness. Many tests and serological techniques have been described to diagnose WNV infection such as complement fixation, neutralization, heamagglutination inhibition, ELISA, and PCR for molecular confirmation. The latter far outweighs the limitations inherent in the other tests. WNV infection is being reported from Vellore for the first time after 1968. This paper aims to describe four cases of WNV infection causing central nervous system manifestations with its molecular characterization. West Nile virus infection was diagnosed with the available molecular techniques such as PCR and sequencing, which emphasizes the need for considering West Nile virus in the differential diagnosis of acute meningoencephalitis and the wider availability of molecular diagnostic tests.

Tuberculous pseudoaneurysm of the ascending aorta.

Increase in the incidence of drug resistance and association with HIV has led to a resurgence of tuberculosis. However, tubercular arteritis continues to remain a rare entity with a prelidection for the thoracic aorta. We report a tubercular ascending aortic pseudoaneurysm in a patient already on treatment for disseminated tuberculosis who underwent successful surgical repair and also review literature pertaining to this entity.