Association of Albuminuria With Chronic Kidney Disease Progression in Persons With Chronic Kidney Disease and Normoalbuminuria : A Cohort Study.

BACKGROUND: Albuminuria is a major risk factor for chronic kidney disease (CKD) progression, especially when categorized as moderate (30 to 300 mg/g) or severe (>300 mg/g). However, there are limited data on the prognostic value of albuminuria within the normoalbuminuric range (<30 mg/g) in persons with CKD. OBJECTIVE: To estimate the increase in the cumulative incidence of CKD progression with greater baseline levels of albuminuria among persons with CKD who had normoalbuminuria (<30 mg/g). DESIGN: Multicenter prospective cohort study. SETTING: 7 U.S. clinical centers. PARTICIPANTS: 1629 participants meeting criteria from the CRIC (Chronic Renal Insufficiency Cohort) study with CKD (estimated glomerular filtration rate [eGFR], 20 to 70 mL/min/1.73 m2) and urine albumin-creatinine ratio (UACR) less than 30 mg/g. MEASUREMENTS: Baseline spot urine albumin divided by spot urine creatinine to calculate UACR as the exposure variable. The 10-year adjusted cumulative incidences of CKD progression (composite of 50% eGFR decline or kidney failure [dialysis or kidney transplantation]) from confounder adjusted survival curves using the G-formula. RESULTS: Over a median follow-up of 9.8 years, 182 of 1629 participants experienced CKD progression. The 10-year adjusted cumulative incidences of CKD progression were 8.7% (95% CI, 5.9% to 11.6%), 11.5% (CI, 8.8% to 14.3%), and 19.5% (CI, 15.4% to 23.5%) for UACR levels of 0 to less than 5 mg/g, 5 to less than 15 mg/g, and 15 mg/g or more, respectively. Comparing persons with UACR 15 mg/g or more to those with UACR 5 to less than 15 mg/g and 0 to less than 5 mg/g, the absolute risk differences were 7.9% (CI, 3.0% to 12.7%) and 10.7% (CI, 5.8% to 15.6%), respectively. The 10-year adjusted cumulative incidence increased linearly based on baseline UACR levels. LIMITATION: UACR was measured once. CONCLUSION: Persons with CKD and normoalbuminuria (<30 mg/g) had excess risk for CKD progression, which increased in a linear fashion with higher levels of albuminuria. PRIMARY FUNDING SOURCE: None.

Microscopy based methods for characterization, drug delivery, and understanding the dynamics of nanoparticles.

Nanomedicine is an emerging field that exploits nanotechnology for the development of novel therapeutic and diagnostic modalities. Researches are been focussed in nanoimaging to develop noninvasive, highly sensitive, and reliable tools for diagnosis and visualization in nanomedical field. The application of nanomedicine in healthcare requires in-depth understanding of their structural, physical and morphological properties, internalization inside living system, biodistribution and localization, stability, mode of action and possible toxic health effects. Microscopic techniques including fluorescence-based confocal laser scanning microscopy, super-resolution fluorescence microscopy and multiphoton microscopy; optical-based Raman microscopy, photoacoustic microscopy and optical coherence tomography; photothermal microscopy; electron microscopy (transmission electron microscope and scanning electron microscope); atomic force microscopy; X-ray microscopy and, correlative multimodal imaging are recognized as an indispensable tool in material research and aided in numerous discoveries. Microscopy holds great promise in detecting the fundamental structures of nanoparticles (NPs) that determines their performance and applications. Moreover, the intricate details that allows assessment of chemical composition, surface topology and interfacial properties, molecular, microstructure, and micromechanical properties are also elucidated. With plethora of applications, microscopy-based techniques have been used to characterize novel NPs alongwith their proficient designing and adoption of safe strategies to be exploited in nanomedicine. Consequently, microscopic techniques have been extensively used in the characterization of fabricated NPs, and their biomedical application in diagnostics and therapeutics. The present review provides an overview of the microscopy-based techniques for in vitro and in vivo application in nanomedical investigation alongwith their challenges and advancement to meet the limitations of conventional methods.

In silico dynamics of COVID-19 phenotypes for optimizing clinical management.

Understanding the underlying mechanisms of COVID-19 progression and the impact of various pharmaceutical interventions is crucial for the clinical management of the disease. We developed a comprehensive mathematical framework based on the known mechanisms of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, incorporating the renin-angiotensin system and ACE2, which the virus exploits for cellular entry, key elements of the innate and adaptive immune responses, the role of inflammatory cytokines, and the coagulation cascade for thrombus formation. The model predicts the evolution of viral load, immune cells, cytokines, thrombosis, and oxygen saturation based on patient baseline condition and the presence of comorbidities. Model predictions were validated with clinical data from healthy people and COVID-19 patients, and the results were used to gain insight into identified risk factors of disease progression including older age; comorbidities such as obesity, diabetes, and hypertension; and dysregulated immune response. We then simulated treatment with various drug classes to identify optimal therapeutic protocols. We found that the outcome of any treatment depends on the sustained response rate of activated CD8+ T cells and sufficient control of the innate immune response. Furthermore, the best treatment-or combination of treatments-depends on the preinfection health status of the patient. Our mathematical framework provides important insight into SARS-CoV-2 pathogenesis and could be used as the basis for personalized, optimal management of COVID-19.

Greulich and Pyle atlas: a non-reliable skeletal maturity assessment method in the North Indian population.

Forensic age assessments are crucial in the evaluation of criminal responsibility and preventing false age claims. Of all the methods available, the Greulich and Pyle (GP) atlas is most commonly used for age estimation purposes. Therefore, the current study sought to analyze the reliability and applicability of the GP standard and, additionally, to determine any possible association between the socioeconomic status (SES), food habits, and estimated skeletal maturity in the North Indian population. The study included 627 (334 males and 293 females) healthy children up to 19 years of age with varying SES and food habits. The skeletal age (SA) was estimated by three different evaluators using the GP atlas. The chronological mean age (CA) and SA were compared in different age cohorts. A paired t-test and a Pearson chi-square test were applied to show the difference between CA and estimated SA and the association of skeletal maturity with SES and food habits. The estimated skeletal age in males was retarded by 0.142 years or 1.72 months (p ≤ 0.05), whereas in females, it was retarded by 0.259 years or 3.12 months (p ≤ 0.05). In males, the GP method has significantly underestimated SA in age cohorts 3-4, 4-5, 6-7, 7-8, 8-9, and 12-13, whereas it overestimated in 10-11 and 18-19 years. However, in females, the SA was significantly underestimated in age groups 10-11, 12-13, and 14-15, respectively. Estimated skeletal maturity had no significant association with SES and food habits. The current study concludes that the GP atlas may not be applicable to North India's population. The observed difference in assessed skeletal maturity may be due to geographical region, genetics, hormonal effects, etc., which require further investigation. Hence, population-specific standards are necessary to determine the bone age of Indian children accurately.

Prokaryotic maintenance respiration and growth efficiency field patterns reproduced by temperature and nutrient control at mesocosm scale.

The distribution of prokaryotic metabolism between maintenance and growth activities has a profound impact on the transformation of carbon substrates to either biomass or CO2 . Knowledge of key factors influencing prokaryotic maintenance respiration is, however, highly limited. This mesocosm study validated the significance of prokaryotic maintenance respiration by mimicking temperature and nutrients within levels representative of winter and summer conditions. A global range of growth efficiencies (0.05-0.57) and specific growth rates (0.06-2.7 d-1 ) were obtained. The field pattern of cell-specific respiration versus specific growth rate and the global relationship between growth efficiency and growth rate were reproduced. Maintenance respiration accounted for 75% and 15% of prokaryotic respiration corresponding to winter and summer conditions, respectively. Temperature and nutrients showed independent positive effects for all prokaryotic variables except abundance and cell-specific respiration. All treatments resulted in different taxonomic diversity, with specific populations of amplicon sequence variants associated with either maintenance or growth conditions. These results validate a significant relationship between specific growth and respiration rate under productive conditions and show that elevated prokaryotic maintenance respiration can occur under cold and oligotrophic conditions. The experimental design provides a tool for further study of prokaryotic energy metabolism under realistic conditions at the mesocosm scale.

Association of the Urine-to-Plasma Urea Ratio With CKD Progression.

RATIONALE & OBJECTIVES: The urine-to-plasma (U/P) ratio of urea is correlated with urine-concentrating capacity and associated with progression of autosomal dominant polycystic kidney disease. As a proposed biomarker of tubular function, we hypothesized that the U/P urea ratio would also be associated with progression of more common forms of chronic kidney disease (CKD). STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: 3,723 adults in the United States with estimated glomerular filtration rate (eGFR) of 20-70 mL/min/1.73 m2, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. EXPOSURE: U/P urea ratio, calculated from 24-hour urine collections and plasma samples at baseline. OUTCOME: Associations of U/P urea ratio with eGFR slope, initiation of kidney replacement therapy (KRT), and CKD progression, defined as 50% decline in eGFR or incident KRT. ANALYTICAL APPROACH: Multivariable linear mixed-effects models tested associations with eGFR slope. Cox proportional hazards models tested associations with dichotomous CKD outcomes. RESULTS: The median U/P urea ratio was 14.8 (IQR, 9.5-22.2). Compared with participants in the highest U/P urea ratio quintile, those in the lowest quintile had a greater eGFR decline by 1.06 mL/min/1.73 m2 per year (P < 0.001) over 7.0 (IQR, 3.0-11.0) years of follow-up observation. Each 1-SD lower natural log-transformed U/P urea ratio was independently associated with CKD progression (HR, 1.22 [95% CI, 1.12-1.33]) and incident KRT (HR, 1.22 [95% CI, 1.10-1.33]). Associations differed by baseline eGFR (P interaction = 0.009). Among those with an eGFR ≥30 mL/min/1.73 m2, each 1-SD lower in ln(U/P urea ratio) was independently associated with CKD progression (HR, 1.30 [95% CI, 1.18-1.45]), but this was not significant among those with eGFR <30 mL/min/1.73 m2 (HR, 1.00 [95% CI, 0.84-1.20]). LIMITATIONS: Possibility of residual confounding. Single baseline 24-hour urine collection for U/P urea ratio. CONCLUSIONS: In a large and diverse cohort of patients with common forms of CKD, U/P urea was independently associated with disease progression and incident kidney failure. Associations were not significant among those with advanced CKD at baseline.

Euglycemic Diabetic Ketoacidosis Caused by Alcoholic Pancreatitis and Starvation Ketosis.

Starvation ketosis and pancreatitis are uncommon and underrecognized etiologies of euglycemic diabetic ketoacidosis (DKA). Euglycemic DKA is associated commonly with pregnancy, use of insulin en route to the hospital, and use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors. A 58-year-old male with past medical history of type II diabetes mellitus and alcoholism presented with chief complaint of nausea, vomiting, and poor oral intake for several weeks. Despite extensive history of diabetes and no recent SGLT-2 inhibitor use, his labs were consistent with euglycemic DKA. His imaging and clinical history also confirmed alcoholic pancreatitis. The patient was admitted for euglycemic DKA secondary to starvation ketosis and alcoholic pancreatitis. His anion gap and beta-hydroxybutyrate rapidly cleared with initiation of the DKA protocol. This case teaches us that clinicians should consider early initiation of the DKA protocol even in the setting of euglycemia, when a patient presents with high-anion-gap metabolic acidosis, a high beta-hydroxybutyrate level, and a clinical picture of pancreatitis and starvation.

Comparison of T2-weighted and diffusion-weighted imaging for the diagnosis of placenta accreta spectrum abnormality.

BACKGROUND: Diffusion-weighted imaging (DWI) is feasible in prenatal imaging, and it exhibits better contrast between the placenta and the myometrium compared to T2-weighted (T2W) images. PURPOSE: To compare magnetic resonance imaging (MRI) features of placenta accreta on T2W and DW imaging. MATERIAL AND METHODS: In this retrospective study, 42 pregnant patients who underwent prenatal MRI were included. MRI was performed on a Siemens 1.5-T scanner. T2W and DWI sequences in the axial, sagittal, and/or coronal planes were compiled for review. Two radiologists independently interpreted T2W and DW images for placenta accreta. T2W and DWI scores were calculated based on the presence of features and graded as low, intermediate, and high risk. The association between imaging features and placental invasion on pathology was calculated using chi-square tests. Sensitivity, specificity, and positive and negative predictive values (NPV) were compared between T2W and DWI interpretations. Inter-reader agreement between the two radiologists for T2W and DWI scores was calculated using Cohen's kappa coefficient. RESULTS: Out of 42 pregnant patients, 10 were pathologically/surgically proven to have placenta accreta. There were no significant differences between T2W and DWI interpretations. Considering a cutoff >6 as positive, the T2W score had higher sensitivity (90% vs. 80%) and NPV (96.9% vs. 94.1%) than the DWI score. The specificity and positive predictive value were 100% for both scores. The inter-reader agreement of T2W score was higher (k = 0.943 vs. 0.882). CONCLUSION: T2W and DWI are comparable in diagnosing placenta accreta spectrum. T2W sequences have higher sensitivity, NPV, and inter-reader agreement than DWI.

Aldosterone in chronic kidney disease and renal outcomes.

AIMS: Randomized controlled trials have demonstrated the efficacy of mineralocorticoid receptor (MR) antagonism in delaying chronic kidney disease (CKD) progression in diabetes; however, they have not investigated the role of aldosterone or whether these beneficial effects could be achieved in individuals without diabetes. METHODS AND RESULTS: The association between serum aldosterone concentrations and kidney disease progression was investigated among 3680 participants in the Chronic Renal Insufficiency Cohort. The primary outcome was CKD progression [defined as the composite of 50% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease, whichever occurred first]. The associations between serum aldosterone and kidney disease outcomes were assessed using Cox proportional hazard models. At baseline, higher aldosterone concentrations were associated with a lower eGFR, lower serum potassium, greater urinary potassium, and protein excretion. Over a median follow-up of 9.6 years, 1412 participants developed CKD progression. In adjusted models, each doubling of serum aldosterone was associated with a 11% increased risk of CKD progression [hazard ratio (HR) 1.11, 95% confidence interval (CI) 1.04-1.18]. Individuals with the highest quartile of serum aldosterone had a 45% increased risk of CKD progression (HR 1.45, 95% CI 1.22-1.73) compared with the lowest quartile. The risk for CKD progression was similar regardless of whether patients had concomitant diabetes (P-interaction = 0.10). CONCLUSION: Higher serum aldosterone levels among individuals with CKD are independently associated with an increased risk for kidney disease progression, irrespective of concomitant diabetes. These findings provide mechanistic support for MR antagonists in delaying CKD progression and suggest that they may also have a role in those without diabetes.

Exploration of in vitro cytotoxic and in ovo antiangiogenic activity of ethyl acetate extract of Penicillium oxalicum.

Fungal endophytes have established new paradigms in the area of biomedicine due to their ability to produce metabolites of pharmacological importance. The present study reports the in vitro cytotoxic and in ovo antiangiogenic activity of the ethyl acetate (EA) extract of Penicillium oxalicum and their chemical profiling through Gas Chromatography-Mass Spectrometry analysis. Treatment of the EA extract of P. oxalicum to the selected human breast cancer cell lines (MDA-MB-231 and MCF-7) leads to the reduced glucose uptake and increased nitric oxide production suggesting the cytotoxic activity of EA extract of P. oxalicum. Our results further show that treatment of EA extract of P. oxalicum attenuates the colony number, cell migration ability and alters nuclear morphology in both the human breast cancer cell lines. Furthermore, the treatment of EA extract of P. oxalicum mediates apoptosis by increasing the expression of BAX, P21, FADD, and CASPASE-8 genes, with increased Caspase-3 activity. Additionally, in ovo chorioallantoic membrane (CAM) assay showed that the treatment of EA extract of P. oxalicum leads to antiangiogenic activity with perturbed formation of blood vessels. Overall, our findings suggest that the EA extract of P. oxalicum show in vitro cytotoxic and antiproliferative activity against human breast cancer cell lines, and in ovo antiangiogenic activity in CAM model.

Rapid Arene Triazene Chemistry for Macrocyclization.

Here, we report a novel rapid arene triazene strategy for the macrocyclization of peptides that generates an inbuilt chromophoric triazene moiety at the site of cyclization within a minute. The rapid arene triazene chemistry is chemoselective for secondary amines and p-amino phenylalanine. Importantly, the resulting triazene cyclic peptide is highly stable at neutral pH and under harsh conditions but rapidly responds to various external stimuli such as UV radiations and acidic conditions, resulting in the ring opening to generate the linear peptides in an unchanged form, which further cyclizes under neutral pH conditions. This method works with completely unprotected peptides and has been applied for the synthesis of 18- to 66-membered monocycles and bicycles with various amino acid compositions in one pot under neutral pH conditions. Due to the high stability of triazene cyclic peptides, the postcyclization modification was carried out with various functional groups. This rapid, macrocyclization strategy featuring a triazene scaffold, amenable to late-stage diversification and responsive to external stimuli, should find application in various fields of chemical biology, selective drug delivery, and identification of cyclic peptide hits after library screening.

Initial comparative analysis of pulmonary involvement on HRCT between vaccinated and non-vaccinated subjects of COVID-19.

OBJECTIVES: To compare the high-resolution computed tomography (HRCT)-derived severity score in COVID-19 patients between those who had earlier received the vaccine against the SARS-CoV-2 and those who did not. METHODS: A retrospective cross-sectional analysis of HRCT of the chest was done in correlation with the vaccination status of clinically diagnosed COVID-19 patients. The variable under evaluation was the CT severity score, whereby differential analysis of the variability on this parameter between incompletely (single dose) vaccinated, completely (both doses) vaccinated, and non-vaccinated individuals was the outcome. RESULTS: The analysis included 826 patients of which 581 did not receive any vaccination whereas 196 patients received incomplete (single dose) vaccination and 49 received complete vaccination. Mean CT severity score was lower in completely vaccinated patients (3.5 ± 6.3) vis-à-vis incompletely vaccinated (10.1 ± 10.5) and non-vaccinated (10.1 ± 11.4) individuals. The mean CT score was significantly lower in completely vaccinated patients of lower ages (≤ 60 years) compared to patients above that age. The incidence of severe disease (CT score ≥ 20) was significantly higher in the incompletely vaccinated and non-vaccinated patients compared to that in the completely vaccinated group. CONCLUSIONS: CT severity scores in individuals receiving both doses of SARS-CoV-2 vaccination were less severe in comparison to those receiving a single dose of vaccine or no vaccine at all. KEY POINTS: • Patients who received complete two doses of vaccination had significantly low mean CT scores compared to the partially vaccinated patients and non-vaccinated patients. • The mean CT scores were significantly lower in completely vaccinated patients of lower ages (< 60 years) while patients > 60 years did not show significantly different CT scores between the vaccinated and non-vaccinated groups. • Consolidations and ground-glass opacities were significantly lower in the group receiving complete vaccination as compared to the unvaccinated and incompletely vaccinated patients.

Tubo-ovarian mass with raised CA-125 in a 21-year-old female.

INTRODUCTION: Peritonitis associated with fungal species Curvularia lunata seldom occurs with only five cases reported in the literature, all in middle-age patients with comorbidities undergoing dialysis. CASE REPORT: A 21-year-old female who was referred to surgical oncology OPD with a diagnosis of ovarian malignancy, based on raised cancer antigen 125 (CA 125) and suspected tubo-ovarian mass (TOM) on magnetic resonance imaging (MRI). A review of the MRI showed a pelvic collection with TOM, suggestive of infective pathology. Fungal culture and mass spectroscopy of the cystic collection identified the presence of Curvularia lunata. She was treated with oral itraconazole which showed symptomatic improvement and radiological response. In the follow-up period, the patient developed chest wall swelling, aspiration and geneXpert® revealed multidrug-resistant (MDR) tuberculosis, and treatment was started. CONCLUSIONS: Unusual causes of TOM and raised CA 125 should be kept in mind when dealing with young patients, as the possibility of epithelial ovarian cancer in this age is very low.

TFE3-associated perivascular epithelioid cell tumor with complete response to mTOR inhibitor therapy: report of first case and literature review.

BACKGROUND: Perivascular epitheloid cell tumor (PEComas) are characterized by expression of both muscles, most often smooth muscle actin (in ~80% of cases) and melanocytic markers (mainly HMB-45 and Melan A). TFE 3-associated PEComas are new variant which are poorly defined due to their limited reports in literature. These tumors lack response to targeted mTOR inhibitor therapy due to lack of mutation in TSC gene. Hereby, we are reporting a case of TFE3 associated pelvic PEComa showing excellent response to Everolimus. CASE PRESENTATION: A 45-year-old female presented with complaint of abdominal mass and bleeding per vaginum for 4 months. She had a history of total abdominal hysterectomy 3 years back in view of abnormal uterine bleeding and exploratory laprotomy 7 months back to remove some pelvic mass. Imaging suggested of ill-defined heterogenous mass of 9.3 x 9.2 x 16 cm involving the uterus, cervix, and upper 1/3 vagina. Multiple omental and peritoneal deposits were also seen, making probable diagnosis of carcinoma endometrium. USG guided biopsy showed cores of fibrous tissue with the presence of cells in sheets with granular eosinophillic cytoplasm; IHC showed positivity for TFE-3, H Caldesmon, GATA-3, and Melan A- and HMB-45; and Ki 67 index was 35%. The basis of above diagnosis of PEComa was made and she was started on Everolimus; repeat imaging after 3 months of therapy showed complete response. CONCLUSION: We are reporting first case of malignant pelvic TFE 3 PEComa showing response to mTOR therapy. Identification of TFE 3 PEComa is important because they showed different biologic behavior then their conventional PEComa.

Evaluation of sample pooling for diagnosis of COVID-19 by real time-PCR: A resource-saving combat strategy.

BACKGROUND AND OBJECTIVES: Although about 80% of coronavirus disease-2019 (COVID-19) cases are reported to be mild, the remaining 20% of cases often result in severe disease with the potential of crushing already overstrained health care services. There has been sustainable growth of COVID-19 cases worldwide since mid-May 2020. To keep tabs on community transmission of COVID-19 infection screening of the samples from a large population is needed which includes asymptomatic/symptomatic individuals along with the migrant population. This requires extra resources, man power, and time for detection of severe acute respiratory syndrome coronavirus 2 by real-time polymerase chain reaction (RT-PCR). In the current scenario, the pooled sample testing strategy advocated by the Indian Council of Medical Research, New Delhi is a new approach that is very promising in resource-limited settings. In this study, we have evaluated the pooled strategy in terms of accurate testing results, utilization of consumables, and identification of borderline positive cases. MATERIALS AND METHODS: Between April and June 2020, we performed COVID-19 testing by RT-PCR from areas with varying prevalence of population referred to COVID laboratory, Dr Ram Manohar Lohia Institute of Medical Sciences, Lucknow. In the first step, the samples are collated into pools of 5 or 10. These pools are tested by RT-PCR. Negative pools were reported as negative whereas positive pools of 5 and 10 are then deconvoluted and each sample is tested individually. RESULTS: In the present study, we tested 4620 samples in 462 pools of 10 and 14 940 samples in 2990 pools of 5. Among 10 samples pool, 61 (13%) pools flagged positive in the first step. In the second step, among 61 pools (610 samples) deconvoluted strategy was followed in which 72 individual samples came positive. The pooled-sample testing strategy helps saves substantial resources and time during surge testing and enhanced pandemic surveillance. This approach requires around 76% to 93% fewer tests done in low to moderate prevalence settings and group sizes up to 5-10 in a population, compared to individual testing. CONCLUSIONS: Pooled-sample PCR analysis strategies can save substantial resources and time for COVID-19 mass testing in comparison with individual testing without compromising the resulting outcome of the test. In particular, the pooled-sample approach can facilitate mass screening in the early coming stages of COVID-19 outbreaks, especially in low- and middle-income settings, and control the spread by meticulous testing of all risk groups.

Yangia mangrovi sp. nov., a novel member of the Roseobacter clade isolated from mangrove soil and emended description of Yangia pacifica Dai et al. 2006.

During a study of the bacterial diversity of mangrove habitats, a novel Gram-stain-negative, rod-shaped bacterium designated as SAOS 153DT was isolated. Sequence alignment and molecular phylogenetic analyses based on 16S rRNA and core gene sequence of strain SAOS 153DT with closely related taxa revealed a sequence identity of 99.4 % and clustering with Yangia pacifica DX5-10T. The fatty acids summed feature 8 (C18:1 ω7c/C18:1 ω6c) and the lipids phosphatidylglycerol, phosphatidylethanolamine and an unknown phospholipid were the major components of the cell wall. The only ubiquinone type present was Q-10. The genomic DNA G+C content of the strain calculated from whole genome sequencing was 66.9 mol%. These chemotaxonomic and genomic characteristics supported the molecular phylogenetic analysis and placed the strain well within the radiation of the genus Yangia. The overall genome related indices using digital DNA-DNA hybridization (35.4 %) and ortho-average nucleotide identity (88.1 %) values were much lower than the recommended thresholds for species delineation, which further consolidated the novel species status of strain SAOS 153DT within the genus Yangia as Yangia mangrovi sp. nov. The type strain is SAOS 153DT (=JCM 31345T=KCTC 52280T=MTCC 12749T).

Comparative study between idiopathic and non-idiopathic dystonia: a prospective observational study.

BACKGROUND: There are very few studies based on the updated dystonia classification. However, a comparison of the idiopathic and non-idiopathic dystonias based on the newer classification has not been done previously. OBJECTIVES: To study and compare the clinicoetiological profile of patients with idiopathic and non-idiopathic dystonia attending a movement disorder clinic of a tertiary care teaching institution. METHODS: All the consecutive dystonia patients from October 2017 to September 2019 fulfilling the inclusion criteria were subjected to a detailed clinical evaluation. Investigations were performed as per requirement. Patients were classified according to the consensus update on phenomenology and classification of dystonia. RESULTS: A total of 183 patients with dystonia were included, with 61.7% (113) males and 38.3% (70) females. The idiopathic group revealed a significantly earlier age of onset with cases slightly outnumbering (n = 96/183, 52.5%) the non-idiopathic group (n = 87/183, 47.5%). Focal dystonias were the commonest type in both the idiopathic (n = 58/96, 60.4%) and non-idiopathic groups (n = 30/87, 34.5%), while generalized dystonia accounted for 26.4% (n = 23/87) of the non-idiopathic cases and only 3.1% (n = 3/96) of the idiopathic cases. The majority of idiopathic cases were isolated dystonia (n = 93/96, 96.9%), while all hemidystonias were non-idiopathic. CONCLUSION: Focal dystonias were the commonest in both idiopathic and non-idiopathic groups, while generalized dystonia was significantly commoner in the non-idiopathic group. Acquired causes like drugs, perinatal insult were the commonest etiology in the non-idiopathic group. Hemidystonia was found exclusively in the non-idiopathic acquired group.

Halocatena pleomorpha gen. nov. sp. nov., an extremely halophilic archaeon of family Halobacteriaceae isolated from saltpan soil.

A novel archaeal strain designated as SPP-AMP-1T was isolated from saltpan soil, using the serial dilution method on a halophilic archaeal medium supplemented with ampicillin. Cells were both rod-shaped and pleomorphic in nature, non-motile, unable to produce acid from a variety of sugars or grow anaerobically with different substrates (l-arginine) and electron acceptors (DMSO, nitrate). Optimal growth was observed at 42 °C, 3.4-4.2 M NaCl and pH 7.2. Cells did not lyse in distilled water and grew in the absence of Mg2+ ions. Phylogenetic analysis based on the sequences of 16S rRNA gene, amino acid sequence of ß'-subunit of RNA polymerase and 400 conserved proteins retrieved from the whole genome assemblies showed that strain SPP-AMP-1T was distantly related to any existing genera within the family Halobacteriaceae. MK-8 was the only quinone detected. Polar lipid analysis showed a unique combination of diethyl derivatives of phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, glycosyl-mannosyl-glucosyl diether and sulphated glycosyl-mannosyl-glucosyl diether as the major lipids. The G+C content of genomic DNA is 57.7 mol%. The phenotypic, phylogenetic and genomic data supported the concept of the novel genus status of strain SPP-AMP-1T in the family Halobacteriaceae for which the name Halocatena pleomorpha gen. nov., sp. nov., is proposed; the type strain is SPP-AMP-1T (=JCM 31368T=KCTC 4276T=MTCC 12579T).

Shedding Light on COVID-19: ADAM17 the Missing Link?

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a rapidly expanding global health crisis. A disintegrin and metalloproteinase 17 (ADAM17), an ectodomain sheddase, is a key component of ACE2 modulation and plays a complex role in inflammation and immunosurveillance. AREAS OF UNCERTAINTY: Much remains unknown regarding the immunopathogenesis of COVID-19, including how the virus affects ADAM17 expression, activity, and regulation. SEARCH STRATEGY: Three electronic databases (MEDLINE through PubMed, Embase through Ovid, and Google Scholar) were searched to identify articles relevant to ADAM17 and severe acute respiratory syndrome coronavirus 1 and 2. Relevant articles published from January 1, 2005, to April 30, 2020, were selected, and reference lists were screened and cross-referenced. We also searched preprint studies on medRxiv and bioRxiv given the rapidly evolving data on COVID-19 SARS-CoV-2. THERAPEUTIC OPINION: Infection with SARS-CoV-2 may lead to an increase in ADAM17 sheddase activity contributing to an exuberant macrophage-predominant inflammatory response and diminished immunosurveillance capacity for viral clearance. Emerging data suggest severe lung injury in COVID-19 is associated with higher levels of TNF-α and IL-6, T-cell lymphopenia and exhaustion, hypercoagulability, and a macrophage-predominant immune response. This clinical picture is consistent with dysregulation of many of the molecular pathways in which ADAM17 participates. CONCLUSIONS: Elucidation of the role of ADAM17 in COVID-19 may identify novel molecular targets for drug development and therapeutic repurposement.

Non-lactate strong ion difference and cardiovascular, cancer and all-cause mortality.

Objectives: Non-lactate strong ion difference (SID) has been shown to be associated with predictors of mortality in intensive care unit. However, the existence of any association between non-lactate SID (nlSID) and all cause, cardiovascular and cancer mortality has not been explored before in community dwelling US adults. Methods: In a nationally representative cross-sectional survey of the US non-institutionalized population, all adult participants (≥20 years of age) using National Health and Nutrition Examination Survey data (1999-2010) combined with National Death Index for mortality status through December 2011. Cox proportional hazard models were built to estimate the hazard ratios for cardiovascular, cancer, and all-cause mortality for each unit increase in non-lactate SID. The models were adjusted for demographic and confounder variables. Results: In the study population the mean (SD) age was 49.6 (18.4) years. Of the study population, 31,475 (91.5%) were alive and 2,893 (8.4%) died during the mean (SD) follow-up period of 5.5 (3.5) years. In univariate regression model using nlSID as continuous variable, we found 2% (unadjusted hazard ratio, HR=1.02; 95% CI, 1.004-1.05) increase in all-cause but not in cardiovascular and cancer mortality (HR=1.03; 95% CI, 0.99-1.08, HR=1.01; 95% CI, 0.97-1.06). After adjusting for potential confounders, we found 7% (adjusted HR=1.07; 95% CI, 1.04-1.10), 5% (HR=1.05; 95% CI, 1.00-1.11) and 7% (HR=1.07; 95% CI, 1.02-1.12) increase in all-cause, cardiovascular, and cancer mortality. Conclusions: A high nlSID is associated with an increase in cardiovascular, cancer and all-cause mortality and may be a prognostic indicator of mortality in general adult population. These findings may provide a point of reference for further studies.