Outcome of substitutional urethroplasty by using dorsal onlay buccal mucosal graft: our experience of 10 years

Background: The term urethral stricture is anterior urethral disease, or a scarring process involving the spongy erectile tissue of the corpus spongiosum. Methods: Total 127 patients were included in the study. Patient selection criteria for urethroplasty by using buccal mucosal graft was length of stricture more than 2 cm, deep spongiofibrosis, failed optical urethrotomy for 3 times, adequate oral hygiene and proper buccal mucosa. Results: Length of stricture varied from 3.2 to 14 cm. In first postoperative week, 20.47% (n=26) patients developed minor wound infection culture negative seroma formation in stitch line in the skin. Donor site complications like eating and drinking difficulty, dysguesia, pain, sensitivity, speaking disorders were not found in any patient while oral tightness was noted in 43.30% (n=55) of patients. On postoperative follow-up mean peak urinary flow rate (Qmax) was 28.0 ml/sec (range 20.0-30.6 ml/sec). After a mean follow-up of 8.8 months range (1 month to 33 months) overall success rate was 90.55% (n=115). Conclusions: Buccal mucosa is an excellent graft material for substitution free graft urethroplasty in case of long anterior urethral stricture with excellent success rate. Success rate of dorsal onlay substitution free buccal mucosal graft urethroplasty is affected by length of stricture and aetiology of strictures. Lichen sclerosus having moderate success rate of urethroplasty and higher rate of complication and failure rate in 1-stage buccal mucosal urethroplasty and can be considered for two stage urethroplasty in case of very long stricture of anterior urethra of lichen sclerosus origin

GeneFEAST: the pivotal, gene-centric step in functional enrichment analysis interpretation

Summary: GeneFEAST, implemented in Python, is a gene-centric functional enrichment analysis summarisation and visualisation tool that can be applied to large functional enrichment analysis (FEA) results arising from upstream FEA pipelines. It produces a systematic, navigable HTML report, making it easy to identify sets of genes putatively driving multiple enrichments and to explore gene-level quantitative data first used to identify input genes. Further, GeneFEAST can compare FEA results from multiple studies, making it possible, for example, to highlight patterns of gene expression amongst genes commonly differentially expressed in two sets of conditions, and giving rise to shared enrichments under those conditions. GeneFEAST offers a novel, effective way to address the complexities of linking up many overlapping FEA results to their underlying genes and data, advancing gene-centric hypotheses, and providing pivotal information for downstream validation experiments. Availability: GeneFEAST is available at https://github.com/avigailtaylor/GeneFEAST Contact: [email protected]: Main text: 3 pages, 1 figure. Supplementary Information: 16 pages, 3 figures, 2 tables, 4 boxe

Inclusion of carbohydrate antigen 242 in addition to carbohydrate antigen 19.9 in serological workup of carcinoma gall bladder: a case series analysis

Background: Common antigenic pool is seen because of shared embryonic origins of gall bladder cancer (GBC) and pancreas. Hence, we analyzed the role of serum carbohydrate antigen 242 (CA242) which has been studied in pancreatic cancer, in GBC. The objectives were to identify whether serum CA242 provides added advantage in diagnosis of GBC when compared to controls and to determine its cut-off value. Methods: Serum CA 19-9 level was determined by chemiluminescent micro particle assay and CA242 by enzyme linked immunosorbent assay (ELISA) of age matched cases and controls. Results: Total enrolled patients were 83 including 10 (11.7%) healthy volunteers, 22 (25.9%) chronic cholecystitis cases, and 53 (62.4%) patients with histological evidence of carcinoma. Mean age of presentation of GBC was 51.64 SD10.88 years with F: M ratio of 5.6:1. Pain (90.6%, 48/53) accompanied with jaundice was significantly associated with GBC well reflected by significantly raised serum total bilirubin (p=0.011), direct bilirubin (p=0.008) along with alkaline phosphatase levels (p=0.001). Significantly higher median value of CA 19-9 and CA242 was observed in GBC when compared to CC and healthy volunteers (p<0.001) with a significant correlation between tumor size (>2.5 cm) and serum levels of CA242. The best cut-off limit for CA242 was 45.25 IU/ml. The specificity for carcinoma diagnosis increased to 100% when CA242 was included along with CA 19.9 in serological estimation. Conclusions: We recommend that CA antigen 19-9 may be complimented with CA242 for serological identification of malignancy in the gall bladder

Improving Automatic Melanoma Diagnosis using Deep Learning-Based Segmentation of Irregular Networks

Deep Learning Has Achieved Significant Success in Malignant Melanoma Diagnosis. These Diagnostic Models Are Undergoing a Transition into Clinical Use. However, with Melanoma Diagnostic Accuracy in the Range of Ninety Percent, a Significant Minority of Melanomas Are Missed by Deep Learning. Many of the Melanomas Missed Have Irregular Pigment Networks Visible using Dermoscopy. This Research Presents an Annotated Irregular Network Database and Develops a Classification Pipeline that Fuses Deep Learning Image-Level Results with Conventional Hand-Crafted Features from Irregular Pigment Networks. We Identified and Annotated 487 Unique Dermoscopic Melanoma Lesions from Images in the ISIC 2019 Dermoscopic Dataset to Create a Ground-Truth Irregular Pigment Network Dataset. We Trained Multiple Transfer Learned Segmentation Models to Detect Irregular Networks in This Training Set. a Separate, Mutually Exclusive Subset of the International Skin Imaging Collaboration (ISIC) 2019 Dataset with 500 Melanomas and 500 Benign Lesions Was Used for Training and Testing Deep Learning Models for the Binary Classification of Melanoma Versus Benign. the Best Segmentation Model, U-Net++, Generated Irregular Network Masks on the 1000-Image Dataset. Other Classical Color, Texture, and Shape Features Were Calculated for the Irregular Network Areas. We Achieved an Increase in the Recall of Melanoma Versus Benign of 11% and in Accuracy of 2% over DL-Only Models using Conventional Classifiers in a Sequential Pipeline based on the Cascade Generalization Framework, with the Highest Increase in Recall Accompanying the Use of the Random Forest Algorithm. the Proposed Approach Facilitates Leveraging the Strengths of Both Deep Learning and Conventional Image Processing Techniques to Improve the Accuracy of Melanoma Diagnosis. Further Research Combining Deep Learning with Conventional Image Processing on Automatically Detected Dermoscopic Features is Warranted

Nanocolumnar Crystalline Vanadium Oxide-Molybdenum Oxide Antireflective Smart Thin Films with Superior Nanomechanical Properties

Vanadium oxide-molybdenum oxide (VO-MO) thin (21-475 nm) films were grown on quartz and silicon substrates by pulsed RF magnetron sputtering technique by altering the RF power from 100 to 600 W. Crystalline VO-MO thin films showed the mixed phases of vanadium oxides e.g., V2O5, V2O3 and VO2 along with MoO3. Reversible or smart transition was found to occur just above the room temperature i.e., at similar to 45-50 degrees C. The VO-MO films deposited on quartz showed a gradual decrease in transmittance with increase in film thickness. But, the VO-MO films on silicon exhibited reflectance that was significantly lower than that of the substrate. Further, the effect of low temperature (i.e., 100 degrees C) vacuum (10(-5) mbar) annealing on optical properties e.g., solar absorptance, transmittance and reflectance as well as the optical constants e.g., optical band gap, refractive index and extinction coefficient were studied. Sheet resistance, oxidation state and nanomechanical properties e.g., nanohardness and elastic modulus of the VO-MO thin films were also investigated in as-deposited condition as well as after the vacuum annealing treatment. Finally, the combination of the nanoindentation technique and the finite element modeling (FEM) was employed to investigate yield stress and von Mises stress distribution of the VO-MO thin films

A Dual Receptor Crosstalk Model of G-Protein-Coupled Signal Transduction

Macrophage cells that are stimulated by two different ligands that bind to G-protein-coupled receptors (GPCRs) usually respond as if the stimulus effects are additive, but for a minority of ligand combinations the response is synergistic. The G-protein-coupled receptor system integrates signaling cues from the environment to actuate cell morphology, gene expression, ion homeostasis, and other physiological states. We analyze the effects of the two signaling molecules complement factors 5a (C5a) and uridine diphosphate (UDP) on the intracellular second messenger calcium to elucidate the principles that govern the processing of multiple signals by GPCRs. We have developed a formal hypothesis, in the form of a kinetic model, for the mechanism of action of this GPCR signal transduction system using data obtained from RAW264.7 macrophage cells. Bayesian statistical methods are employed to represent uncertainty in both data and model parameters and formally tie the model to experimental data. When the model is also used as a tool in the design of experiments, it predicts a synergistic region in the calcium peak height dose response that results when cells are simultaneously stimulated by C5a and UDP. An analysis of the model reveals a potential mechanism for crosstalk between the Gαi-coupled C5a receptor and the Gαq-coupled UDP receptor signaling systems that results in synergistic calcium release

Novel 3‑Methyleneisoindolinones Diversified via Intramolecular Heck Cyclization Induce Oxidative Stress, Decrease Mitochondrial Membrane Potential, Disrupt Cell Cycle, and Induce Apoptosis in Head and Neck Squamous Cell Carcinoma Cells

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer in the world and the most prevalent cancer of developing countries. Increased disease burden and a smaller number of approved targeted therapies are a growing concern worldwide. Isoindolinone motifs have been a central part of many pharmacological compounds, and their derivatives possess substantial anticancer potential. However, their anticancer potential against HNSCC has not been well investigated. In the current study, a series of 3-methyleneisoindolinones have been designed and synthesized and their late-stage intramolecular Heck cyclization was achieved to evaluate their anticancer potential against HNSCC cells. Additionally, in silico ADME profiling of synthesized compounds revealed their drug-likeness properties as potential drug candidates. Among the synthesized compounds, 3-bromo-5-methylpyridin-2-yl-3-methyleneisoindolin-1-one, i.e., 3n, with a pyridyl unit exhibited the most significant cytotoxicity against HNSCC cells. The cytotoxic potential of synthesized compounds varied depending on the nature of substituents present and has been well established with structure–activity relationship studies. Further, flow cytometric analysis showed that 3f, 3h, and 3n triggered intracellular oxidative stress, disrupted mitochondrial membrane potential, and interrupted the cell cycle of HNSCC cells in the S-phase and sub-G1 phase. Further, 3f, 3h, and 3n also exhibited pro-apoptotic potential and induced cellular apoptosis in the HNSCC cells. Overall, the findings of this study attributed 3-methyleneisoindolinone chemistry and efficacy evaluation and corroborated their anticancer potential against HNSCC. It will pave the way to further design and optimize novel 3-methyleneisoindolinone as effective antitumor agents, which may provide effective treatment modalities against HNSCC

Genotypic analysis of multidrug-resistant tuberculosis isolates from extra pulmonary tuberculosis cases in tertiary care centers in Northern India

Objective/background: Multidrug-resistant tuberculosis (MDR-TB) is a major public health problem. The diagnosis of MDR-TB is of paramount importance in establishing appropriate clinical management and infection control measures. Rapid detection of MDR-TB allows the establishment of an effective treatment regimen, minimizes the risk of further resistance, and limits the spread of drug-resistant strains. The aim of this study is to determine the genotypic characterization of MDR-TB isolates from extra pulmonary tuberculosis (EPTB) cases in tertiary care centers in Northern India. Methods: This study was a prospective study. In total, 756 extra pulmonary specimens were collected from patients with suspected tuberculosis in two tertiary care hospitals in Northern India. Specimens were processed for Ziehl–Neelsen staining, culture, and first-line drug susceptibility test using BacT/ALERT 3D system and GenoType MTBDRplus assay for genotypic analysis of MDR-TB. MDR-TB strains were further processed by novel multiplex polymerase chain reaction for rapid identification of Beijing and non-Beijing strains associated with MDR-TB. Results: Of these 164 Mycobacterium tuberculosis complex isolates, 100 (60.9%) strains were fully susceptible and 64 (39.1%) strains were resistant. We noted that the prevalence of MDR-TB among EPTB was 22 (13.4%). The prevalence of MDR-TB was 11.4% in new cases and 19.1% in previously treated cases (p <0.05). Ser531Leu mutation was the predominant mutation noted, and Ser315Thr mutation was more prevalent among the MDR-TB isolates (p <0.05). The proportion of Beijing strains was significantly higher among MDR-TB strains (72.7%, p <0.05). Conclusion: The prevalence (13.4%) of MDR-TB among EPTB was high, and the most prominent mutations in rpoB, katG, and inhA genes were S531L (67.3%), S315T1 (94.5%), and C15T (20%), respectively. Beijing stains are significantly associated with MDR-TB among EPTB in this region. We found that the transmission of prominent mutations contributes to an unexpected increase in primary resistance, including MDR-TB cases in Northern India

Effect of Temporal Variation in Mineralization of Nutrients through Sewage Sludge, Farm Yard Manure and Vermicompost in Soil

Soil amendment by organic matter (O.M.) has been widely accepted as an efficient nutrient-management technique in agriculture. The study was conducted as pot culture experiment at the Rajiv Gandhi South Campus, Barkachha Banaras Hindu University (B.H.U.) Mirzapur, which is located in the Vindhyan zone of Mirzapur district at 25º 10” latitude, 82º 37” longitude with an altitude of 427 meters above the sea level. The soils of the study region are mostly having poor fertility and shallow depth. Different sources of organic manures Sewage Sludge (S.S), Farm Yard Manure (FYM) and Vermi-Compost (V.C.) with different doses (10, 20 and 30 grams) were applied in pot along with soil and were incubated for 90 days. Required amount of water was added to soil in order to keep it moist as and when required. pH, electrical conductivity(E.C) , O.M. and nutrient content (N, P, K and S) had shown significant changes due to different treatments applied in soil. Applications of organic amendments in this study indicated considerable changes in the basic soil physio-chemical properties, different levels of available nutrient and their release pattern. With increase in doses of S.S and V.C. soil pH also increased but, it was decreased with increase in doses of FYM. Increase in the dose of S.S., F.Y.M. and V.C. had increased the E.C. and O.M. of soil. The available N content decreased with increase in the incubation interval. The available P increased from 30 Days After Incubation (DAI) to 60 DAI but it decreased at 90 DAI. Availability of S content increased with increase in duration of incubation period

Case Report Mixed Cutaneous Infection Caused by Mycobacterium szulgai and Mycobacterium intermedium in a Healthy Adult Female: A Rare Case Report

Nontuberculous mycobacteria (NTMs) are ubiquitous and are being increasingly reported as human opportunistic infection. Cutaneous infection caused by mixed NTM is extremely rare. We encountered the case of a 46-year-old female, who presented with multiple discharging sinuses over the lower anterior abdominal wall (over a previous appendectomy scar) for the past 2 years. Microscopy and culture of the pus discharge were done to isolate and identify the etiological agent. Finally, GenoType Mycobacterium CM/AS assay proved it to be a mixed infection caused by Mycobacterium szulgai and M. intermedium. The patient was advised a combination of rifampicin 600 mg once daily, ethambutol 600 mg once daily, and clarithromycin 500 mg twice daily to be taken along with periodic follow-up based upon clinical response as well as microbiological response. We emphasize that infections by NTM must be considered in the etiology of nonhealing wounds or sinuses, especially at postsurgical sites