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.

Stressed Speech Emotion Recognition Using Teager Energy and Spectral Feature Fusion with Feature Optimization.

The objective of speech emotion recognition (SER) is to enhance man-machine interface. It can also be used to cover the physiological state of a person in critical situations. In recent time, speech emotion recognition also finds its operations in medicine and forensics. A new feature extraction technique using Teager energy operator (TEO) is proposed for the detection of stressed emotions as Teager energy-autocorrelation envelope (TEO-Auto-Env). TEO is basically designed for increasing the energies of the stressed speech signals whose energies are reduced during the speech production process and hence used in this analysis. A stressed speech emotion recognition (SSER) system is developed using TEO-Auto-Env and spectral feature combination for detecting the emotions. The spectral features considered are Mel-frequency cepstral coefficients (MFCC), linear prediction cepstral coefficients (LPCC), and relative spectra-perceptual linear prediction (RASTA-PLP). EMO-DB (German), EMOVO (Italian), IITKGP (Telugu), and EMA (English) databases are used in this analysis. The classification of the emotions is carried out using the k-nearest neighborhood (k-NN) classifier for gender-dependent (GD) and speaker-independent (SI) cases. The proposed SSER system provides improved accuracy compared to the existing ones. Average recall is used for performance evaluation. The highest classification accuracy is achieved using the feature combination of TEO-Auto-Env, MFCC, and LPCC features with 91.4% (SI), 91.4% (GD-male), and 93.1%(GD-female) for EMO-DB; 68.5% (SI), 68.5% (GD-male), and 74.6% (GD-female) for EMOVO; 90.6%(SI), 91% (GD-male), and 92.3% (GD-female) for EMA; and 95.1% (GD-female) for IITKGP female database.

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.

A 33-Year-Old Woman With Breathing Difficulty, Inspiratory Wheeze, and Hemoptysis.

CASE PRESENTATION: A 33-year-old teacher from Ghana with no medical comorbidities and no relevant family history came to our pulmonology department with progressive difficulty in breathing, wheezing, and stridor for 6 months. Similar episodes had been treated previously as bronchial asthma. She was being treated with high-dose inhaled corticosteroids and bronchodilators but had no relief. The patient also described two episodes of large quantities of hemoptysis (> 150 mL) in the previous week. A general physical examination revealed a tachypneic young woman with an audible inspiratory wheeze. Her BP was 128/80 mm Hg; pulse, 90 beats/min; and respiratory rate, 32 breaths/min. There was a hard, minimally tender, nodular swelling of 3 × 3 cm in the midline neck felt just below the cricoid cartilage, moving with deglutition and protrusion of the tongue, with no retrosternal extension. There was no cervical or axillary lymphadenopathy. Laryngeal crepitus was present.

How does the cam morphology develop in athletes? A systematic review and meta-analysis.

OBJECTIVE: A higher prevalence of cam morphology has been reported in the athletic population but the development of the cam morphology is not fully understood. The purpose of this systematic review is to establish the timing of development of the cam morphology in athletes, the proximal femoral morphologies associated with its development, and other associated factors. DESIGN: Embase, MEDLINE and the Cochrane Library were searched for articles related to development of the cam morphology, and PRISMA guidelines were followed. Data was pooled using random effects meta-analysis. Study quality was assessed using the Downs and Black criteria and evidence quality using the GRADE framework. RESULTS: This search identified 16 articles involving 2,028 participants. In males, alpha angle was higher in athletes with closed physes than open physes (SMD 0.71; 95% CI 0.23, 1.19). Prevalence of cam morphology was associated with age during adolescence when measured per hip (ß 0.055; 95% CI 0.020, 0.091) and per individual (ß 0.049; 95% CI 0.034, 0.064). Lateral extension of the epiphysis was associated with an increased alpha angle (r 0.68; 95% CI 0.63, 0.73). A dose-response relationship was frequently reported between sporting frequency and cam morphology. There was a paucity of data regarding the development of cam morphology in females. CONCLUSIONS: Very low and low quality evidence suggests that in the majority of adolescent male athletes, osseous cam morphology developed during skeletal immaturity, and that prevalence increases with age. Very low quality evidence suggests that osseous cam morphology development was related to lateral extension of the proximal femoral epiphysis.

On the macro-micro-morphology of organs of host invasion in hemiparasite Helicanthes elasticus (Desv.) Danser.

Loranthaceae family includes hemiparasitic members which are seen invading a wide range of commercial crops. Helicanthes elasticus (Desv.) Danser is very common on mango trees. Though parasitic in nature, this mistletoe is also medicinally important as fetoprotective, against vesicular calculi and kidney infections. This study is an attempt to document macro-microscopical features of parasitic root, fruit and host-mistletoe tissue interaction in the haustorium of H. elasticus growing on mango stems. Collection, preservation, sectioning, staining and photomicrography of the root, fruit and host-mistletoe union were done as per standard methodologies of anatomical studies. Though there is resemblance to the normal roots in morphology as well as anatomy, the microscopic finding of large number of branched stone cells in the roots is interesting. The morpho-anatomical features recorded would help in understanding the infection biology of this mistletoe. The eradication during the earlier stages of its establishment from seed or from the root creeping over the surface of the host can help in controlling this parasite infection on commercially important host plants.

Cardiac Involvement in Vasculotoxic and Neurotoxic Snakebite - A not so Uncommon Complication.

BACKGROUND: Cardiac toxicity following snakebite envenomation has been previously observed, but not studied in detail, especially the involvement in neurotoxic bites. This prospective observational case study evaluates the incidence of cardiac toxicity along with the difference between vasculotoxic and neurotoxic bites and analysing the predictors for development of cardiotoxicity. METHOD: 96 patients who had snake bite envenomation were evaluated for features of cardiotoxicity with clinical features, ECG, echocardiogram and troponin-I levels. RESULTS: Cardiac toxicity was observed in 42.7% of patients, the majority were either ECG changes, noted in 34.3% and rise in troponin-I, noted in 21.9% of patients. Other changes included echocardiographic changes in 4.2%, and Takotsubo cardiomyopathy in 1%. There was no significant difference in the incidence of cardiotoxicity between the neurotoxic (41.7%) and vasculotoxic (42.9%) (p value =1) snake bites, even though the predominant changes seen in neurotoxic snake bites were ECG changes. There were no deaths in the current study. None of the demographic or clinical parameters studied could predict the development of cardiac events. CONCLUSION: Cardiac toxicity is a well defined complication of poisonous snake bite and incidence is more frequent than previously thought. Both vasculotoxic and neurotoxic snake bites are associated with cardiac toxicity and is not associated with increase in mortality.

Effect of Helicanthes elasticus (Desv.) Danser extracts on immune profile of Wistar albino rats.

Helicanthes elasticus (Desv.) Danser is a common type of mistletoes of Indian origin. In Indian traditional and folklore medicines the plant is claimed to possess a range of medicinal values such as immunomodulator, anti-diabetic and anti-microbial properties. However, there is no experimental proof for its therapeutic claim. The aqueous and alcoholic extracts of H. elastica were evaluated for its immuno-modulatory effect on antibody formation against sheep red blood cells and on cell mediated immunity of immunological paw edema model. Ethanolic and aqueous extracts have shown dose dependent elevation in the antibody titer value in comparison to control group at 14th and 21st day of sensitization (**p < 0.01). There is a mild to moderate elevation were observed in the immunological paw edema at highest dose (400 mg/kg) during 21st day after sensitization. The histopathological observation shows that there is an increase in the white pulp of spleen and increased cellularity and formation of distinct germinal cells in lymph node. H. elasticus extracts possess marked antibody formation propensity without significant modification on cell mediated immunity.

Cerebroprotective Potential of Hesperidin Nanoparticles Against Bilateral Common Carotid Artery Occlusion Reperfusion Injury in Rats and In silico Approaches.

Cerebral ischemia-reperfusion (C I/R) accelerates neuronal injury through the overproduction of reactive oxygen species due to mitochondrial dysfunction. Hesperidin has cerebroprotective effects due to its antioxidant and anti-apoptotic nature against oxidative damage caused by C I/R. The blood-brain barrier also limits the hesperidin passage into the cerebral region due to its poor bioavailability. Current research included analysis of binding energy, hesperidin inhibitory constant on inflammatory cytokines (TNF α, IL 6) and apoptotic protein (caspase 3), hesperidin nanoparticles prepared, and investigation of their defense against C I/R rats. Binding energy and IC50 of hesperidin on pathological proteins using AutoDoc. 1.5.6 and PyRx in silico tools were compared with thalidomide. The fabrication method was engaged in the preparing of nano-hesperidin, characterized by SEM assessment. Bilateral common carotid artery occlusion technique has been used in experimental rats to cause C I/R. Nano-hesperidin cerebroprotective activity was assessed by differing infarction magnitude, oxidative stress parameters, TNF α and IL 6, and hippocampal histopathology with rats treated with unformulated hesperidin. Hesperidin found stronger binding strength and IC50 was relative to thalidomide on TNF α, IL 6, and caspase 3. Nano-hesperidin with a size of 100-500 nm was shown in a uniform nano-size and spherical form. Nano-hesperidin-treated rats showed significantly increased glutathione (p < 0.00***), catalase (p < 0.01**), and total protein (p < 0.001***), and decreased cerebral infarction size, TNF α (p < 0.01**), IL 6 (p < 0.01**), and malondialdehyde (p < 0.05*), compared with hesperidin-treated ischemic rats. Therefore, hesperidin nanoparticles may confer protection to the neurons against ischemic injury compared with hesperidin treatment.

Development and application of genomic resources for comparative and translational genomics in legumes through leveraging genomic sequence of Medicago truncatula.

The expressed sequence tags (ESTs) of common bean were BLAST aligned with barred medic genome sequence and developed 1196 conserved intron spanning primers (CISPs) to facilitate genetic studies in legumes. Randomly selected 288 CISPs, representing loci on barrel medic genome, were tested on 10 selected members of legume family. On the source taxa, the highest single copy amplification success rates of 61.8% (barrel medic) and 56.2% (common bean) was obtained. The success rate of markers was 54.5% in cowpea followed by 53.5% in pigeonpea and chickpea, signifying cross taxon amplification and their potential use in comparative genomics. However, relatively low percentages of primer set amplified (40-43%) in soybean, urdbean and peanut. Further, these primers were tested on different varieties of chickpea, pigeonpea and cowpea. The PCR products were sequenced and aligned which resulted in detection of 26 SNPs and eight INDeLs in cowpea, seven SNPs and two INDeLs in chickpea and 27 SNPs and 14 INDeLs in pigeonpea. These SNPs were successfully converted in to size variation for gel-based genotyping. The CISP markers developed in this study are expected to aid in map saturation of legumes and in marker-assisted selection for accelerated crop improvement.

Development of quality standards of medicinal mistletoe - Helicanthes elastica (Desr.) Danser employing Pharmacopoeial procedures.

Helicanthes elastica (Desr.) Danser (Loranthaceae), commonly known as Indian mango mistletoe, is a parasitic shrub found widely growing on mango trees in southern India. Development of monographic quality standards is need of the hour for Pharmacopoeial/extra-Pharmacopoeial and folk medicinal plants. Systematic pharmacognostical evaluation of leaves of H. elastica has been carried out employing Pharmacopoeial procedures of testing herbal drugs. Macro-microscopic features of H. elastica leaf were recorded. Ethanolic extract was tested positive for alkaloids, steroids, carbohydrates, tannins, saponins and phenols. HPTLC fingerprint profile was developed for the identification of extracts using reference standard ß-sitosterol glucoside. Results of the present investigation would serve as a source of pharmacognostical information and a document to control the quality of H. elastica (Desr.) Danser.

Discovery and preclinical development of a novel prodrug conjugate of mesalamine with eicosapentaenoic acid and caprylic acid for the treatment of inflammatory bowel diseases.

Mesalamine (5-ASA) is one of the drugs indicated as first line therapy in ulcerative colitis for induction and maintenance of remission. Sulfasalazine and formulations of 5-ASA (pH-dependent and controlled release formulations) were developed to minimize the systemic absorption and maximize the delivery of the mesalamine to colon. Although, its efficacy and safety is well documented there are approximately 30% nonresponders to 5-ASA therapy. This necessitates the need for novel therapeutic options to improve the efficacy and safety of the currently available 5-ASA therapy. CLX-103 is a novel, patented prodrug molecular conjugate of mesalamine, eicosapentaenoic acid and caprylic acid designed to offer incremental benefits over the currently approved 5-ASA formulations. Results of in vitro and in vivo studies showed that CLX-103, was stable in simulated gastric fluid, but undergoes enzymatic hydrolysis in the small/large intestines to release the active moiety. Our data also showed that the active moiety is retained in the targeted intestinal tissues (ileum and colon) over a longer period of time in relation to sulfasalazine. The in vitro data supports the observed in vivo plasma kinetics of 5-ASA characterized by longer Tmax, low Cmax after the oral administration of CLX-103. Efficacy study of CLX-103 in acute dextran sodium sulfate (DSS) mouse colitis model showed improved potency measured as Disease Activity Index (DAI) and histological scores in the colon as compared to sulfasalazine. These findings indicate that CLX-103 could offer a differentiated drug product which is more efficacious and safer than the currently approved 5-ASA formulations in the treatment of inflammatory bowel diseases.

Carboprost Versus Oxytocin for Active Management of Third Stage of Labor: A Prospective Randomized Control Study.

BACKGROUND AND OBJECTIVES: Postpartum hemorrhage is the single largest and leading cause of maternal morbidity and mortality not only in developing countries but also in developed countries. The present study is an attempt to evaluate the scope of using prophylactic intramuscular carboprost tromethamine 125 µg in comparison with intramuscular oxytocin 10 units for the active management of third stage of labor. MATERIALS AND METHODS: Two hundred pregnant women at term with spontaneous onset of labor were included in the study and were randomly divided into 2 groups of 100 women each. Group A and group B were given injection oxytocin 10 units and injection carboprost tromethamine 125 µg intramuscularly, respectively, at the time of delivery of anterior shoulder. The main outcome measures with respect to third stage of labor were: duration, blood loss by volume, difference in hemoglobin, need for additional oxytocics and side effects. RESULTS: Subjects who received carboprost tromethamine 125 µg showed a significant reduction in duration of third stage of labor (p < 0.05) and blood loss (p < 0.01) when compared to the subjects who received oxytocin 10 units. Likelihood of occurrence of postpartum hemorrhage was reduced without significant side effects except for diarrhea. Additional need for other uterotonics after carboprost was significantly less compared to oxytocin. CONCLUSION: Intramuscular carboprost 125 µg is a better cost-effective alternative as compared to 10 units intramuscular oxytocin in active management of third stage of labor.

Molecular fingerprinting of Helicanthus elastica (Desr.) Danser growing on five different hosts by RAPD.

Mistletoes are hemiparasitic plants growing on aerial parts of other host trees. Many of the mistletoes are reported to be medicinally important. The hemiparasitic nature of these plants makes their chemical composition dependent on the host on which it grows. They are shown to exhibit morphological dissimilarities also when growing on different hosts. Helicanthus elastica (Desr.) Danser (mango mistletoe) is one such less explored medicinal mistletoe found on almost every mango tree in India. Traditionally, the leaves of this plant are used for checking abortion and for removing stones in the kidney and urinary bladder while significant antioxidant and antimicrobial properties are also attributed to this species of mistletoe. The current study was undertaken to evaluate molecular differences in the genomic DNA of the plant while growing on five different host trees using four random markers employing random amplified polymorphic DNA (RAPD) followed by similarity matrix by Jaccard's coefficient and distance matrix by hierarchal clustering analysis. Similarity and distance matrix data employing just 4 random markers, separately and the pooled data as well, revealed significant difference in the genomic DNA of H. elastica growing on five different hosts. Pooled data of similarity from all the 4 primers cumulatively showed similarity between 0.256 and 0.311. Distance matrix ranged from of 0.256 to 0.281 on pooling the data from all the four primers. The result employing a minimum number of primers could conclude that genomic DNA of H. elastica differs depending upon the host on which it grows, hence the host must be considered while studying or utilizing this mistletoe for medicinal purposes.

Identification and introgression of QTLs implicated in resistance to sorghum downy mildew (Peronosclerospora sorghi (Weston and Uppal) C. G. Shaw) in maize through marker-assisted selection.

Sorghum downy mildew caused by Peronosclerospora sorghi is a major disease of maize and resistance is under the control of polygenes which necessitated identification of quantitative-trait loci (QTLs) for initiating marker-assisted introgression of resistant QTLs in elite susceptible inbred lines. In the present study, QTLs for sorghum downy mildew (SDM) resistance in maize were identified based on cosegregation with linked simple sequence repeats in 185 F2 progeny from a cross between susceptible (CM500-19) and resistant (MAI105) parents. F3 families were screened in the National Sorghum Downy Mildew Screening Nursery during 2010 and 2011. High heritability was observed for the disease reaction. The final map generated using 87 SSR markers had 10 linkage groups, spanning a length of 1210.3 cM. Although, we used only 87 SSR markers for mapping, the per cent of genome within 20 cM to the nearest marker was 88.5. Three putative QTLs for SDM resistance were located on chromosomes 3 (bin 3.01), 6 (bin 6.01) and 2 (bin 2.02) using composite interval mapping. The locus on chromosome 3 had a major effect and explained up to 12.6% of the phenotypic variation. The other two QTLs on chromosomes 6 and 2 had minor effects with phenotypic variation of 7.1 and 2%. The three QTLs appeared to have additive effects on resistance. The QTLs on chromosomes 3 and 6 were successfully used in the marker-assisted selection programme for introgression of resistance to SDM in eight susceptible maize lines.

High performance thin layer chromatography qualitative densitometry as a sensitive method to assess shelf life of polyherbal formulations: A study on Hutabhugadi Churna.

INTRODUCTION: Measuring chemical stability of polyherbal formulations is very challenging due to diversity in phytochemical composition. As there are no comprehensive guidelines for stability testing of herbal products, there is a need for a sensitive tool to detect how the quality of herbal products varies with time under the influence of environmental conditions. AIMS: To validate the employability of high-performance thin layer chromatography (HPTLC) for real-time stability of Hutabhugadi Churna (HC). MATERIALS AND METHODS: The chromatograms were developed using toluene/ethyl acetate/formic acid (10:5:1) and ethyl acetate/formic acid (10:1) as a mobile phase for chloroform and ethanolic extract, respectively. The plates were scanned under 254, 366, 540 (pre-derivatization) and 540 nm (post-derivatization). Samples were analyzed immediately after preparation and after 3(rd) and 6(th) months of storage. Alteration of fingerprint profiles from the initial pattern, in terms of number of peaks, was employed as diagnostic tools. Percentage variation in composition at given period was calculated. RESULTS: HC is found to be stable at room temperature up to 1.3 months using the method of calculation of 10% degradation period employing slope and intercept values for the initial, 3(rd) and 6(th) months' deviation in number of bands. The data obtained were subjected to regression analysis in context to number of bands obtained. The curve was found to be linear with R(2) value of 0.89-0.96 supported by their tolerance range of 0.04-0.11. CONCLUSION: The proposed model is a new logic with prospects to become working method for stability assessment of polyherbal formulations under controlled conditions.

Macro-microscopic examination of leaves of Cinnamomum malabatrum (Burm. f.) Blume sold as Tamalapatra.

Leaves of Cinnamomum tamala Nees & Eberm. (Lauraceae) commonly known as 'Tamalapatra' is a highly reputed commodity in drug and spice trade. Its adulteration with other leaf species belonging to genus Cinnamomum is found to be a common practice in India and other parts of the world. Thorough macroscopic and microscopic investigations are essential to differentiate them. Survey of South Indian crude drug markets revealed that in place of C. tamala some other leaves of Cinnamomum species are sold. Fresh leaves of various Cinnamomum species, including C. tamala, growing in south India were collected and studied to establish their correct identity. Leaves sold in markets of S. India under the name of Tamalapatra were subjected for detailed macro-microscopic evaluation including maceration and powder microscopy. Leaves of Cinnamomum malabatrum showed many distinguishing macro-microscopic characters, which will serve as markers to differentiate them from C. tamala the official source of Tamalapatra. Though macroscopy will serve the purpose of identification of the entire drug, microscopy had revealed the identity of the commercial substitute even in fragmented and powdered form. Macro-microscopic identity of C. malabatrum is established in comparison with the official drug, further chemical and biological studies may be confirmative in deciding the leaves as a substitute or adulterant.

Osteoporosis - An Emerging Disease of the 21(st) Century, Part 1: An Overview.

Osteoporosis is a condition where bones are fragile with a poor bone mineral density. This increases the risk of fracture especially of the hip, vertebrae, and wrist. These fractures are usually termed "fragility fractures." In this article, we aim to provide a broad overview of osteoporosis-investigation, management, and prevention.

Carotid intima-media thickness in patients with end-stage renal disease.

Accelerated atherosclerosis and cardiovascular disease are major causes of morbidity and mortality in patients of end-stage renal disease. Carotid intima media thickness is taken as a useful surrogate marker of atherosclerosis. Thirty end-stage renal disease (ESRD) patients were subjected to ultrasonography to study CIMT before the initiation of dialysis. CIMT was found to be higher in ESRD patients than in controls. Levels of a serum marker of oxidative stress were also found to be higher in patients than in the controls. CIMT is an easy, noninvasive, reproducible, and cost-effective investigation in patients with chronic renal failure.