Clinical implications of serum anti-PLA2R levels and glomerular PLA2R deposits in primary membranous nephropathy.

Introduction. The clinical implications of serum anti-PLA2R with glomerular PLA2R deposits in primary membranous nephropathy (PMN) is scarcely reported. Hence the study was designed to demonstrate the prevalence of serum anti-PLA2R levels and PLA2R staining in glomeruli in PMN and the clinical implications of the two parameters. Objectives. Investigate the prevalence of anti PLA2R positivity in PMN. Ascertain correlation between serum anti-PLA2R levels and glomerular staining for PLA2R with clinical and lab parameters in PMN. Patients and Methods. Fifty PMN patients during the period from October 2017 to December 2018 were included. Labs were done and eGFR was calculated as per MDRD 6. Anti-PLA2R titres were done in all patients. Titres more than 20 RU/ml were considered positive. Glomerular staining for PLA2R was graded on fresh frozen tissue by immunofluorescence technique. Results. Anti-PLA2R antibody positivity and glomerular PLA2R deposition was observed in 42% (21/50) and 86% (43/50) patients respectively. 79.3% (23/29) had positive glomerular PLA2R deposition with negative serum anti PLA2R. Positive correlation were observed between serum PLA2R antibody and serum creatinine (p = 0.0001) and urine protein-creatinine ratio levels with tissue PLA2R staining grades (p = 0.04). Negative association was found between serum albumin (p = 0.026) and tissue PLA2R staining grades. Conclusion. Serum anti-PLA2R wasn't a sensitive marker of primary membranous nephropathy in our study group emphasising the need to consider a compendium of serological markers for diagnosis of primary membranous nephropathy and to rely more on glomerular deposition of PLA2R as a better clinical indicator for PMN.

ß-Cyclodextrin capped ZnS nanoparticles for CER-assisted colorimetric and spectrophotometric detection of Pb2⁺, Cu2⁺, and Hg2⁺ in an aqueous solution.

Herein, simple, low-cost, and room-temperature synthesis of beta-cyclodextrin (ß-CD) stabilized zinc sulfide nanoparticle (ZnS NP) through the chemical precipitation method has been reported for cation exchange reaction (CER) based colorimetric sensing of Pb2+, Cu2+, and Hg2+. Formation of ß-CD stabilized ZnS NPs (ZnS@ß-CD) was verified by physicochemical characterization techniques such as XRD, XPS, FE-SEM, and TEM. ZnS@ß-CD NPs showed color change selectively for the metal ions Pb2⁺, Cu2⁺, and Hg2⁺ among the various metal ions including Sn2⁺, Cr³âº, Mn2⁺, Fe³âº, Co2⁺, Ni2⁺, and Cd2⁺. The solubility product of reactants and the transformed products are the reason for selective CER of ZnS@ß-CD NPs towards Pb2⁺, Cu2⁺, and Hg2⁺ ions. ZnS@ß-CD NPs dispersion revealed rapid color change from white to orange, black, and bright yellow on the addition of higher concentrations of Pb2⁺, Cu2⁺, and Hg2⁺ respectively. This color change is due to the formation of complete CER-transformed nanostructures such as PbS, CuS, and HgS in higher concentrations (10⁻1- 10⁻³ M) of corresponding metal ions. The partial CER altered products Zn1-x,PbxS, Zn1-xCuxS and Zn1-xHgxS were detected due to the appearance of pale color in the lower metal ions concentrations of 10⁻4 - 10⁻6 M. This CER assisted transformation was also monitored through spectrophotometric methods. Moreover, infrared spectroscopic analysis was used to testify the structure of CER transformed product. The synthesized ZnS@ß-CD NPs act as an efficient CER-based sensor for distinguishing and determining Pb2⁺, Cu2⁺, and Hg2⁺ at different level concentrations in the aqueous solution.

Correlation of Acoustic Radiation Force Impulse Imaging with Chronicity Markers in Native Renal Biopsy.

Introduction. Acoustic Radiation Force Impulse (ARFI) is an ultrasound parameter which has shown promise in assessing liver stiffness, but there are limited data on the correlation of ARFI with chronicity markers in renal biopsies. Objectives. Determine ARFI values in ultrasound and correlate with chronicity markers in renal biopsy. Determine whether ARFI can be used as a non-invasive chronicity predictor compared to renal length, Resistive Index (RI), and cortical thickness. Patients and Methods. Two hundred and fifty patients were enrolled in the study. The ultrasound variables ARFI, renal length, RI, and cortical thickness values were assessed by the radiologist prior to renal biopsy. The biopsy slides were graded as per the Mayo Clinic consensus report scoring system by an experienced pathologist. Results. Among 250 study participants, 167 were males and 83 were females. IgA nephropathy was the most common pathology (n=47;19%), followed by diabetic nephropathy (n=42;17%), membranous nephropathy (n=35;14%), FSGS (n=27;11%), and MCD (n=19; 8%). The mean eGFR was 55.9 ± 42.12 ml/min/1.73 m2. The average renal length was 10.086 ± 1.01 cm. The average cortical thickness was 0.707 ± 0.134 cm. Resistive index was 0.68 ± 0.09. Acoustic radiation force impulse had weak negative correlation (r=-0.286; p=0.0001) with total pathological score and weak positive correlation with eGFR (r=0.279; p=0.0001). RI was a better indicator for histologically evaluated chronicity with positive correlation coefficient (r=0.416; p=0.0005) compared to renal length, cortical thickness, and ARFI. Conclusion. ARFI didn't corelate with the pathological score in renal biopsies. RI had better predictive value for chronicity in native renal biopsies.

Vulvar Lichen Sclerosus Et Atrophicus: Refractory to Standard Therapy.

Vulvar lichen sclerosus et atrophicus is an inflammatory disease which can affect the pediatric age group, although rarely. Its prevalence is underestimated. It may have genital or extragenital manifestations. If left untreated, it may progress to complications which hamper the quality of life. The treatment of choice is topical clobetasol propionate. Here, we present a case of prepubertal vulvar LS, which was refractory to topical clobetasol but responded to topical tacrolimus application.

Molecular characterization and antifungal activity of lipopeptides produced from Bacillus subtilis against plant fungal pathogen Alternaria alternata.

Over 380 host plant species have been known to develop leaf spots as a result of the fungus Alternaria alternata. It is an aspiring pathogen that affects a variety of hosts and causes rots, blights, and leaf spots on different plant sections. In this investigation, the lipopeptides from the B. subtilis strains T3, T4, T5, and T6 were evaluated for their antifungal activities. In the genomic DNA, iturin, surfactin, and fengycin genes were found recovered from B. subtilis bacterium by PCR amplification. From different B. subtilis strains, antifungal Lipopeptides were extracted, identified by HPLC, and quantified with values for T3 (24 g/ml), T4 (32 g/ml), T5 (28 g/ml), and T6 (18 g/ml). To test the antifungal activity, the isolated lipopeptides from the B. subtilis T3, T4, T5, and T6 strains were applied to Alternaria alternata at a concentration of 10 g/ml. Lipopeptides were found to suppress Alternaria alternata at rates of T3 (75.14%), T4 (75.93%), T5 (80.40%), and T6 (85.88%). The T6 strain outperformed the other three by having the highest antifungal activity against Alternaria alternata (85.88%).

A Mixture Model for Estimating SARS-CoV-2 Seroprevalence in Chennai, India.

Serological assays used to estimate the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) often rely on manufacturers' cutoffs established on the basis of severe cases. We conducted a household-based serosurvey of 4,677 individuals in Chennai, India, from January to May 2021. Samples were tested for SARS-CoV-2 immunoglobulin G (IgG) antibodies to the spike (S) and nucleocapsid (N) proteins. We calculated seroprevalence, defining seropositivity using manufacturer cutoffs and using a mixture model based on measured IgG level. Using manufacturer cutoffs, there was a 5-fold difference in seroprevalence estimated by each assay. This difference was largely reconciled using the mixture model, with estimated anti-S and anti-N IgG seroprevalence of 64.9% (95% credible interval (CrI): 63.8, 66.0) and 51.5% (95% CrI: 50.2, 52.9), respectively. Age and socioeconomic factors showed inconsistent relationships with anti-S and anti-N IgG seropositivity using manufacturer cutoffs. In the mixture model, age was not associated with seropositivity, and improved household ventilation was associated with lower seropositivity odds. With global vaccine scale-up, the utility of the more stable anti-S IgG assay may be limited due to the inclusion of the S protein in several vaccines. Estimates of SARS-CoV-2 seroprevalence using alternative targets must consider heterogeneity in seroresponse to ensure that seroprevalence is not underestimated and correlates are not misinterpreted.

Providing Diabetes Education through Phone Calls Assisted in the Better Control of Hyperglycemia and Improved the Knowledge of Patients on Diabetes Management.

Purpose: A recent single-arm pilot study from our group showed a significant decrease in HbA1C in Type-2 diabetes individuals provided with SMS and phone call-based education on glycemic control. Considering the preference of participants to phone call-based education, a randomized control trial (RCT) with parallel design was conducted to determine the impact of phone call-based diabetes educational intervention on the control of hyperglycemia and improvement in the knowledge about diabetes management. Objectives: To determine the impact of phone call-based educational intervention on the control of hyperglycemia and improvement in the knowledge about diabetes management. Methodology: The study was conducted for a period of 12 months on a total of 273 Type-2 diabetic patients (interventional group (n = 135); non-interventional group (n = 138)) who had provided consent to participate. Subjects in the case group received weekly phone calls on diabetes education; whereas the control group received no education. HbA1C investigations were carried out at baseline and at every fourth month until the completion of the study period for the subjects in both the groups. The impact of phone call-based education was measured by comparing HbA1C values as well as by measuring the questionnaire-based knowledge scores on diabetes management. Results: At the end of the study period, there was a significant reduction in HbA1C in 58.8% participants (n = 65) and a manifold (2-5-fold) increase in knowledge on diabetes management among participants in the case group (n = 110). However, no significant difference in HbA1C and knowledge score was observed in participants from the control group (n = 115). Conclusion: Phone call-based diabetes education is a viable option to empower patients for better management of Type-2 diabetes.

Chemical and biology of sulfur fluoride exchange (SuFEx) click chemistry for drug discovery.

Compounds containing an SF bond have garnered intense interest in the chemical and biological literature. In particular, sulfonyl fluorides (RSO2F) are commonly used as covalent protein inhibitors and biological probes. The introduction of the fluorine atom into drugs often leads to significantly promoted medicinal properties, which revolutionized the development of pharmaceuticals and gained attention because of the beneficial properties of these small and highly electro-negative halogens. The sulfonyl fluoride functional group has also been widely adopted throughout the field of chemical biology due to its unique balance between reactivity and stability under physiological conditions. This comprehensive review highlights the recent developments of sulfonyl fluorides based compounds in a massive range of therapeutic applications. We believe this review article will be helpful to inspire new ideas for structural design and developments of less toxic and potent Sulfur based drugs against the numerous death-causing diseases.

Precision Determination of the Neutral Weak Form Factor of

We report a precise measurement of the parity-violating (PV) asymmetry A_{PV} in the elastic scattering of longitudinally polarized electrons from ^{48}Ca. We measure A_{PV}=2668±106(stat)±40(syst) parts per billion, leading to an extraction of the neutral weak form factor F_{W}(q=0.8733 fm^{-1})=0.1304±0.0052(stat)±0.0020(syst) and the charge minus the weak form factor F_{ch}-F_{W}=0.0277±0.0055. The resulting neutron skin thickness R_{n}-R_{p}=0.121±0.026(exp)±0.024(model) fm is relatively thin yet consistent with many model calculations. The combined CREX and PREX results will have implications for future energy density functional calculations and on the density dependence of the symmetry energy of nuclear matter.

A new cryptic species of Nyctibatrachus (Amphibia, Anura, Nyctibatrachidae) with description of its tadpole from the central Western Ghats, India.

We describe a new species of night frog belonging to the genus Nyctibatrachus from the central Western Ghats, India. Nyctibatrachus tunga sp. nov. is distinguished from all congeners by a combination of (1) body size medium (SVL 37.0-40.2 mm ♂, 42.4-47.4 mm ♀), (2) head wider than long (HW 16.0-17.6 mm ♂, 17.4-20.3 mm ♀, HL 11.7-13.6 mm ♂, 13.4-15.5 mm ♀), (3) skin on dorsal and lateral surfaces with glandular folds and throat with dense glandular longitudinal folds, belly white, (4) webbing on toes medium, reaching the third subarticular tubercle on either side of fourth toe (5) presence of nuptial pad and femoral glands in adult males, (6) dorsal body color dark brown, ventrally buff colored except belly, (7) finger disc weakly developed (fd3 0.8±0.1 mm ♂, 1.0±0.1 mm ♀; fw3 0.5±0.1 mm ♂, 0.8±0.1 mm ♀), (8) toe disc moderately developed (td4 1.2±0.2 mm ♂, 1.6±0.1 mm ♀; tw4 0.8±0.1 mm ♂, 0.7±0.0 mm ♀), (9) third finger disc without dorso-terminal groove, fourth toe disc with dorso-terminal groove cover bifurcate distally. Further, molecular phylogeny based on two mitochondrial genes (16S rRNA and ND1), reveals that the new species is sister taxon to N. vrijeuni and N. shiradi. Based on the analysis of 16S rRNA, the new species is genetically divergent by 2.0% and 2.6% from N. vrijeuni and N. shiradi respectively indicating weak but consistent differences to these two species. The bioacoustic analysis also indicated that the new species differed from one of its closest congeners, N. vrijeuni by a higher dominant frequency in advertisement calls. At present, Nyctibatrachus tunga sp. nov. is known from streams within evergreen forests and coffee estates of the upper catchment areas of river Tunga in central Western Ghats.

Testing for nonlinearity in nonstationary time series: A network-based surrogate data test.

The classical surrogate data tests, which are used to differentiate linear noise processes from nonlinear processes, are not suitable for nonstationary time series. In this paper, we propose a surrogate data test that can be applied on both stationary time series as well as nonstationary time series with short-term fluctuations. The method is based on the idea of constructing a network from the time series, employing a generalized symbolic dynamics method introduced in this work, and using any one of the several easily computable network parameters as discriminating statistics. The construction of the network is designed to remove the long-term trends in the data automatically. The network-based test statistics pick up only the short-term variations, unlike the discriminating statistics of the traditional methods, which are influenced by nonstationary trends in the data. The method is tested on several systems generated by linear or nonlinear processes and with deterministic or stochastic trends, and in all cases it is found to be able to differentiate between linear stochastic processes and nonlinear processes quite accurately, especially in cases where the common methods would lead to false rejections of the null hypothesis due to nonstationarity being interpreted as nonlinearity. The method is also found to be robust to the presence of experimental or dynamical noise of a moderate level in an otherwise nonlinear system.

Acute Neuroendocrine Profile in Predicting Outcomes in Severe Traumatic Brain Injury: A Study from a Tertiary Care Center in South India.

BACKGROUND: Pituitary dysfunction following severe traumatic brain injury (sTBI) is significant and may be correlated with the outcomes. AIMS AND OBJECTIVES: This study aimed to evaluate the early changes in pituitary hormone levels after sTBI and to correlate with outcomes in terms of severity and mortality. METHODS: This was a prospective, observational study, involving consecutive patients of 16-60 years, with sTBI (Glasgow Coma Scale GCS < 9) presenting to the hospital within 24 h of trauma. Demographic and clinical data were collected. Serum samples were collected in the morning (08-10 am) on day 1 and day 4 for cortisol, thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), and prolactin (Chemiluminescence immunoassay). Outcome was assessed in terms of mortality (which included both immediate and at 3 months) and Glasgow outcome scale at 3 months. RESULTS: 54 patients were studied. Mean cortisol on day 4 was 28.5 µg/dL in alive patients and 13.7 µg/dL in patients deceased at 3 months (P < 0.001). Patients who were deceased at 3 months had significantly lower T3 on day 4 (0.973 vs 1.4 ng/dL) and lower T4 (8.1 µg/L vs 6.1 µg/dL) as compared to patients who survived (P = 0.049 and 0.005, respectively). Acute phase TSH on day 4 levels were significantly lower in patients deceased at 3 months. There was no significant difference in the prolactin levels. CONCLUSION: Day 4 cortisol, T3, T4, and TSH correlated with the outcomes at 3 months and hence have predictive value post-sTBI.

Jejunojejunal Intussusception at Birth: A Rare Clinical Scenario.

We report a case of intussusception presenting as bilious vomiting in a term neonate. Intussusception should be considered as a differential diagnosis even in the neonatal period. Ultrasound scan may help in early diagnosis. This condition needs to be operated early as delayed treatment may lead to bowel necrosis.

Accurate Determination of the Neutron Skin Thickness of

We report a precision measurement of the parity-violating asymmetry A_{PV} in the elastic scattering of longitudinally polarized electrons from ^{208}Pb. We measure A_{PV}=550±16(stat)±8(syst) parts per billion, leading to an extraction of the neutral weak form factor F_{W}(Q^{2}=0.00616 GeV^{2})=0.368±0.013. Combined with our previous measurement, the extracted neutron skin thickness is R_{n}-R_{p}=0.283±0.071 fm. The result also yields the first significant direct measurement of the interior weak density of ^{208}Pb: ρ_{W}^{0}=-0.0796±0.0036(exp)±0.0013(theo) fm^{-3} leading to the interior baryon density ρ_{b}^{0}=0.1480±0.0036(exp)±0.0013(theo) fm^{-3}. The measurement accurately constrains the density dependence of the symmetry energy of nuclear matter near saturation density, with implications for the size and composition of neutron stars.

An Update on Advances in COVID-19 Laboratory Diagnosis and Testing Guidelines in India.

The declaration of COVID-19 as a global pandemic has warranted the urgent need for technologies and tools to be deployed for confirming diagnosis of suspected cases. Diagnostic testing for COVID-19 is critical for understanding epidemiology, contract-tracing, case management, and to repress the transmission of the SARS-CoV-2. Currently, the Nucleic Acid Amplification Test (NAAT)-based RT-PCR technique is a gold standard test used for routine diagnosis of COVID-19 infection. While there are many commercially available RT-PCR assay kits available in the market, selection of highly sensitive, specific, and validated assays is most crucial for the accurate diagnosis of COVID-19 infection. Laboratory diagnosis of SARS-CoV-2 is extremely important in the disease and outbreak management. Development of rapid point of care tests with better sensitivity and specificity is the critical need of the hour as this will help accurate diagnosis and aid in containing the spread of SARS-CoV-2 infection. Early detection of viral infection greatly enhances implementation of specific public health intervention, such as infection control, environmental decontamination, and the closure of specific high-risk zones. Large-scale sequencing of SARS-CoV-2 genome isolated from affected populations across the world needs to be carried to monitor mutations that might affect performance of molecular tests. Creation of genome repositories and open-source genetic databases for use by global researchers is clearly the way forward to manage COVID-19 outbreak and accelerate vaccine development. This review summarizes various molecular diagnostics methods, technical guidelines, and advanced testing strategies adopted in India for laboratory diagnosis of COVID-19.

Comparison between Dexmedetomidine and Clonidine as an Adjuvant to Ropivacaine in Ultrasound-Guided Adductor Canal Block for Postoperative Analgesia in Total Knee Replacement: A Randomized Controlled Trial.

Background: Total knee replacement (TKR) surgeries are associated with significant postoperative pain. Ultrasound-guided adductor canal block is associated with better pain scores. The addition of Clonidine and Dexmedetomidine as additives to local anesthetics was the recent focus of interest. However, there are minimal studies comparing the duration of analgesia as additives to Ropivacaine in ultrasound-guided adductor canal block for TKRs. Materials and Methods: Prospective, randomized, double-blind design was followed. One hundred and two American Society of Anesthesiologists I to III patients undergoing unilateral TKR surgeries were included in the study and randomized into two groups. Group C received Clonidine 150 mcg and Group D received Dexmedetomidine 100 mcg as an add on to 30 mL of 0.2% ropivacaine for adductor canal block. Postoperatively, duration of analgesia, sedation score, rescue analgesic requirement, hemodynamics, and any other adverse effects were monitored. Results: The total duration of analgesia in Group D (16.01 h [standard deviation [S. D]-0.5]) was significantly higher as compared to Group C (13.02 h [S. D-0.5]) (P < 0.0001). The numerical rating score (NRS) was significantly lower in Group D compared to Group C (P < 0.05) at multiple postoperative timelines. Group D (2.25(S. D-0.44)) had better sedation scores as compared to Group C (2 [S. D-0]) (P = 0.001). Conclusion: Dexmedetomidine has longer duration, lower pain, and better sedation scores as compared to clonidine in adductor canal blocks for postoperative pain relief in TKR surgeries.

Minimally invasive transforaminal lumbar interbody fusion: Technical tips, learning curve, short-term clinical outcome, and brief review.

BACKGROUND: Current trends in spine surgeries have shifted to minimally invasive procedures. Minimally invasive approaches are getting more popular for lumbar interbody fusion procedures. OBJECTIVES: The objective of the study was to report technical modifications, learning curve, and short-term clinical results in minimally invasive transforaminal interbody fusion (MITLIF). MATERIALS AND METHODS: All MITLIF cases performed from 2018 July to March 2020 were included. First three authors were operating surgeons. Visual analog scores (VAS) scoring for pain, Macnab criteria, and Oswestry disability index (ODI) were used for outcome assessment. Operating time, radiation exposure, and complications were assessed separately in a group of 20 as per time sequence in series to assess the learning curve. RESULTS: A total of 61 patients were included. Various indications included spondylolisthesis, failed back surgery, calcified lumbar disc, and spondylodiscitis. Mean age was 47.08 ± 12.06. Intraoperative blood loss was 97.04 ± 25.58. Mean operating time and number of C-arm shots were 190.75 ± 37.11 and 159.3 ± 74.54, respectively, in initial 20 cases which however reduced in later operated cases. Significant improvement in VAS and ODI scores was observed at follow-up of 6.34 ± 4.67 months. Three cases needed surgical revision in the initial 20 cases, and there were no revision surgeries in later operated cases. CONCLUSION: MITLIF could be done in failed back surgery cases, spondylodiscitis, and deformity corrections in addition to spondylolisthesis. It has advantages of less injury to soft tissues, maintaining the posterior tension band, decrease in blood loss and hospital stays, and early mobilization. However, it has longer learning curve and takes minimum 20 cases for the surgeon to acquire reasonable experience and confidence.