IL-21 plays an important role in modulating "Th17-Treg" cell axis in leprosy Type 1 reactions.

Leprosy type 1 reaction (T1R) is a cell-mediated inflammatory reaction which involves skin and peripheral nerves in leprosy. Lesions with T1R have higher production of IL-17 cytokine from CD4+ T cells along with lower TGF-ß producing FOXP3+ CD4+ Tregs. IL-21 is an important cytokine that promotes the development and stability of Th17 cells in an autocrine manner. It can play an important role in the pathogenesis of T1R in leprosy. However, the mechanism by which IL-21 influences the pathogenic progress of leprosy T1R remains poorly understood. In the present study, we evaluated the expression of IL-21 cytokine in skin lesions of both non-reactional (NR) and T1R via immuno-histochemistry and quantitative PCR (qPCR). Further, expression of various genes (IL-17A, IL-17F, TGF-ß, FOXP3, RORC and IL-21) was also measured by qPCR in cultured cells. We also analyzed the secretion of various cytokines such as of IL-21, IL-17A/F and TGF-ß in the culture supernatants by ELISA. In addition, differentiation of Th17 and Treg cells were studied in PBMC cultures after stimulation with Mycobacterium leprae sonicated antigens and rIL-21 for 48 hrs and the phenotypes of Th17 and Tregs were determined by flowcytometric analysis. Our results clearly indicate that IL-21+T cells were significantly higher in both peripheral blood and skin lesions of T1R as compared to NR patients. Moreover, we observed that recombinant IL-21 cytokine inhibited TGF-ß producing Treg cells differentiation along with up-regulating Th17 cells under in-vitro conditions. The gene expression of IL-21 was significantly negatively correlated with Treg and positively correlated with Th17 cell markers in T1R patients. Our results suggested that IL-21 promotes T1R mediated inflammation via modulating the balance of Th17 and Treg cell populations.

Role of GeneXpertMTB/RIF in the diagnosis of cutaneous tuberculosis.

BACKGROUND: cutaneous involevemtn is an important extrapulmonary manifestation of tuberculosis. It is a paucibacillary condition and has diverse clinical presentations. Sufficient data is not available regarding role of GeneXpertMTB/RIF in cutanoues tuberculosis. METHODS: in this study, BacT/Alert3D and response to antitubercular therapy were taken as gold standard and performance of GeneXpertMTB/RIF was evaluated against it in clinically and histopathologically suspected cases of cutaneous tuberculosis. RESULTS: forty seven patients were included in the study of which commonest presentation was scrofuloderma (42.6%) followed by lupus vulgaris (40.4%). Granulomatous inflammation on histopathology was seen in 75.5% patients on skin biopsy. Sic patients had extracutaneous focus of tuberculosis. In 14 (29.79%), culture of skin biopsy was positive for M. tuberculosis and all showed complete response to ATT in 6 months. GeneXpertMTB/RIF detected M. tuberculsois in 4 samples. CONCLUSION: GeneXpertMTB/RIF is not a reliable tool for diagnosis of cutaneous tuberculosis. Clinic-histopathological correlation along with response to ATT is needed for confirmation of diagnosis of cutaneous tuberculosis.

Transcriptomic landscaping of core genes and pathways of mild and severe psoriasis vulgaris.

Psoriasis is a common chronic inflammatory skin disease affecting >125 million individuals worldwide. The therapeutic course for the disease is generally designed upon the severity of the disease. In the present study, the gene expression profile GSE78097, was retrieved from the National Centre of Biotechnology (NCBI)­Gene Expression Omnibus (GEO) database to explore the differentially expressed genes (DEGs) in mild and severe psoriasis using the Affy package in R software. The Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways of the DEGs were analysed using clusterProfiler, Bioconductor, version 3.8. In addition, the STRING database was used to develop DEG­encoded proteins and a protein­protein interaction network (PPI). Cytoscape software, version 3.7.1 was utilized to construct a protein interaction association network and analyse the interaction of the candidate DEGs encoding proteins in psoriasis. The top 2 hub genes in Cytohubba plugin parameters were validated using immunohistochemical analysis in psoriasis tissues. A total of 382 and 3,001 dysregulated mild and severe psoriasis DEGs were reported, respectively. The dysregulated mild psoriasis genes were enriched in pathways involving cytokine­cytokine receptor interaction and rheumatoid arthritis, whereas cytokine­cytokine receptor interaction, cell cycle and cell adhesion molecules were the most enriched pathways in severe psoriasis group. PL1N1, TLR4, ADIPOQ, CXCL8, PDK4, CXCL1, CXCL5, LPL, AGT, LEP were hub genes in mild psoriasis, whereas BUB1, CCNB1, CCNA2, CDK1, CDH1, VEGFA, PLK1, CDC42, CCND1 and CXCL8 were reported hub genes in severe psoriasis. Among these, CDC42, for the first time (to the best of our knowledge), has been reported in the psoriasis transcriptome, with its involvement in the adaptive immune pathway. Furthermore, the immunoexpression of CDK1 and CDH1 proteins in psoriasis skin lesions were demonstrated using immunohistochemical analysis. On the whole, the findings of the present integrated bioinformatics and immunohistochemical study, may enhance our understanding of the molecular events occurring in psoriasis, and these candidate genes and pathways together may prove to be therapeutic targets for psoriasis vulgaris.

The Association of Metabolic Syndrome and Psoriasis: A Systematic Review and Meta-Analysis of Observational Study.

BACKGROUND: Metabolic syndrome worsens complications in psoriasis patients by predisposing them to cardiovascular diseases. Psoriasis has been widely associated with metabolic syndrome; however, it has still not been proven owing to a limited number of studies and some of those reporting conflicting results. OBJECTIVE: Psoriasis has reportedly been associated with metabolic syndrome; however, it has yet not been established beyond doubt owing to conflicting literature. The present meta-analysis of observational studies aims to evaluate the prevalence of metabolic syndrome in psoriasis patients and establish an inferring point that psoriasis patients are certainly susceptible to metabolic syndrome. The study will benefit clinicians to assess and monitor psoriasis patients for several associated comorbid conditions and in its treatment. METHODS: A systematic web search for 'Psoriasis', 'Metabolic Syndrome', 'Hypertension', 'Plasma Glucose', 'Dyslipidaemia', 'Waist Circumference' was performed, collecting all original observational studies on humans up to April 30, 2018. Depending on the inclusion and exclusion criteria, articles were screened for eligibility. Due to the presence of significant heterogeneity, the Odds Ratio (OR) was calculated using a random-effect model with Der-Simonian and Laird method. The statistical heterogeneity was determined using I2 statistics. Comprehensive Meta-Analysis Software, Version 3 was used to perform all the analysis. RESULTS: Sixty-three studies encompassing 15,939 psoriasis patients and 103,984 controls were included in this meta-analysis. Among them, 30.29 % of psoriasis patients were reported with metabolic syndrome in comparison to 21.70 % of subjects in the control group. The present study clearly indicates an increased prevalence of metabolic syndrome among psoriasis patients (OR: 2.077 [95% CI, 1.84 - 2.34]). CONCLUSION: The findings support the fact that psoriasis patients have a higher incidence of metabolic syndrome. Our study also recommends that psoriasis patients should be regularly monitored for metabolic syndrome complications and its associated risk factors such as hypertension, raised triglyceride, lowered HDL Cholesterol, increased fasting plasma glucose, and waist circumference.

Evaluation of reliability of self-collected vaginal swabs over physician-collected samples for diagnosis of bacterial vaginosis, candidiasis and trichomoniasis, in a resource-limited setting: a cross-sectional study in India.

OBJECTIVES: Self-collected vaginal swabs can facilitate diagnosis of vaginal discharge (VD) in resource-limited settings, provided reliability of the method is established. The aim of this study was to evaluate the concordance between self-collected and physician-collected vaginal swabs for aetiological diagnosis of VD and to determine the prevalence of bacterial vaginosis (BV), vulvovaginal candidiasis (VVC) and trichomonas vaginitis (TV). METHODS: A total of 550 females (median age: 32 years; range: 18-45 years) attending two sexually transmitted infection/reproductive tract infection (STI/RTI) clinics with VD from January 2015 to May 2016 were included in the study after obtaining written informed consent. Swabs were self-collected by patients after instructions and subsequently by a physician under speculum examination. Samples were processed for standard bedside tests, Gram staining, wet mount and culture (gold standard) according to the national guidelines. Concordance between the two methods was determined by the Cohen's kappa value. RESULTS: BV, VVC and TV were diagnosed in 79 (14.4%), 144 (26.2%) and 3 (0.5%) patients, respectively. VVC coexisted with BV in 58 (10.5%) patients. There was no coinfection of TV with BV or VVC. Candida albicans was isolated in 84 (58.3%) VVC cases. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of self-collected swabs for diagnosing BV was 91.1%, 100%, 100% and 98.5%, respectively, while for the C. albicans VVC and TV, sensitivity, specificity, PPV and NPV all were 100% as compared with physician-collected swabs. Highly concordant results were obtained between two methods by the Kappa values of 0.95 (BV), 0.99 (VVC) and 1.0 (TV). CONCLUSION: The comparative performance of self-collected and physician-collected vaginal swabs establishes self-collection of samples for BV, VVC and TV as a viable alternative tool in the management of STIs/RTIs, especially in peripheral and resource-constrained settings. This would be effective in implementing the diagnostic approaches for STIs/RTIs in community-based surveillance studies at national or regional level and therefore strengthening the National STI/RTI Control Programme.

Effects of air pollution on the skin: A review.

The increase in air pollution over the years has had major effects on the human skin. Various air pollutants such as ultraviolet radiation, polycyclic aromatic hydrocarbons, volatile organic compounds, oxides, particulate matter, ozone and cigarette smoke affect the skin as it is the outermost barrier. Air pollutants damage the skin by inducing oxidative stress. Although human skin acts as a biological shield against pro-oxidative chemicals and physical air pollutants, prolonged or repetitive exposure to high levels of these pollutants may have profound negative effects on the skin. Exposure to ultraviolet radiation has been associated with extrinsic skin aging and skin cancers. Cigarette smoke contributes to premature aging and an increase in the incidence of psoriasis, acne and skin cancers. It is also implicated in allergic skin conditions such as atopic dermatitis and eczema. Polyaromatic hydrocarbons are associated with extrinsic skin aging, pigmentation, cancers and acneiform eruptions. Volatile organic compounds have been associated with atopic dermatitis. Given the increasing levels of air pollution and its detrimental effects on the skin, it is advisable to use strategies to decrease air pollution.

How Reliable Is Microscopy and Culture for the Diagnosis of Gonorrhea? An 11-Year Experience from INDIA.

Positivity of microscopy and culture was greater (P < 0.0001) in men with urethral discharge syndrome (65.8%) than in women with vaginal/cervical discharge (0.5%), indicating that basic diagnostic tests may not be cost-effective for diagnosis of vaginal/cervical discharge syndrome. Microscopy when compared with culture showed sensitivity, specificity, positive predictive value and negative predictive value of 95.4%, 77.6%, 84.6%, and 95.3%, in men, whereas in women, it was 77.8%, 99.9%, 92.1%, and 99.9%, respectively.

Asymptomatic solitary cutaneous mastocytoma: a rare presentation.

A 50-day-old female child presented with asymptomatic skin colored raised lesion on the dorsal aspect of the left wrist since the age of 10 days. The diagnosis of cutaneous mastocytoma was made based upon clinical and histopathological features.

Circumcision.

Circumcision is one of the oldest and the most controversial surgical procedures performed worldwide and is almost universal among Muslim and Jewish men. Most medical institutions in various countries agree that although there may be health benefits, there is no medical justification for routine circumcision in neonates or children. It should be performed only for established medical reasons and should not be universally recommended. There are modern techniques that provide safer, simpler, quicker, and cheaper alternatives to the traditional means of circumcision with good functional and cosmetic results. Female genital mutilation (FGM) includes procedure that alters or injures female genital organs for nonmedical reasons. Various degrees of FGM are prevalent, the most mutilating one being infibulation. There are numerous gynecologic and obstetrical complications with infibulation. FGM also plays a significant role in facilitating the transmission of HIV infection through numerous mechanisms. Health care providers have an important role to play in the eradication of this practice. Increased professional and public awareness about such a practice is required.

Activation of the p38 Map kinase pathway is essential for the antileukemic effects of dasatinib.

Dasatinib, a dual Src/Abl tyrosine kinase inhibitor, has significant antileukemic effects against various imatinib mesylate-resistant BCR/ABL mutants. Despite well-documented inhibitory effects of dasatinib on BCR/ABL kinase, the exact downstream cellular events leading to generation of its potent antileukemic effects remain to be defined. We provide evidence that p38 Map kinase (MAPK) pathway is activated leading to increased upregulation of mixed lineage kinase 3, MKK3/6, MSK1, and Mapkapk2, upon treatment of BCR/ABL expressing cells with dasatinib, including cells expressing various imatinib-resistant mutants, except for T315I. Our data demonstrate that such dasatinib-dependent activation of p38 MAPK and its effectors plays a critical role in the generation of antileukemic responses, since pharmacological inhibition of p38 or siRNA-mediated knockdown of its expression reverse dasatinib-mediated apoptosis, cell cycle arrest, and anti-proliferative effects. p38 MAPK inhibition also reversed dasatinib-induced suppression of CML patient-derived leukemic colony-forming units progenitor growth in vitro, as well as BCR/ABL expressing KT-1 cell-derived leukemic progenitor growth. Altogether, our findings suggest a critical role for p38 MAPK pathway in the generation of antileukemic effects of dasatinib, and raise the possibility that development of novel means to enhance p38 MAPK activation in BCR/ABL expressing cells may be an approach to promote antileukemic responses and, possibly, reverse T315I mutation-mediated resistance.

Late presentation of CardioSEAL PFO closure device fracture and thrombus formation three years after device implantation.

Transcatheter closure of patent foramen ovale (PFO) is a promising alternative to surgical closure or anticoagulation therapy in patients with a history of cryptogenic stroke. Although a number of transcatheter closure devices have been developed and used outside of the United States, the two commonly used devices in the United States are the StarFLEX CardioSEAL and the Amplatzer Occluder. Several complications, both early and late, associated with the devices have been reported in 6-11% of patients. The rates of complication vary with the different devices. Complications include device-related thrombi, embolization, device malposition, fracture, air embolism, arrhythmias, pericardial effusion, need for surgical intervention and death. As reported in the literature, the incidence of longterm complications beyond 1 year is rare. We report a case of a very late presentation of CardioSEAL device arm fracture associated with left atrial thrombus 3 years after device implantation.

Changing trends in sexually transmitted infections at a Regional STD Centre in north India.

BACKGROUND & OBJECTIVES: Sexually transmitted infections (STIs) a major public health problem in India show various trends in different parts of the country. However, there are limited data on the changing profile of laboratory proven STIs in the same clinic over the years. The present study was thus aimed to determine the changing trends of the profile of STIs and HIV seropositivity in STD clinic attendees over a 15 yr period, and also to detect change, if any, in the antimicrobial resistance pattern of Neisseria gonorrhoeae. METHODS: The STIs were diagnosed clinically and confirmed by standard laboratory techniques. Socio-demographic data were collected through pre-designed proformae. The STI profile and HIV seropositivity were compared between 1990-1993 (A), 1994-1997 (B), 1998-2001 (C) and 2002-2004 (D). Antimicrobial resistance pattern of N. gonorrhoeae was determined by standard techniques and compared between the last three periods. RESULTS: Of the 78,617 STD attendees, 12,709 (16.2%) had STIs. During period A, genital discharges and during B, C and D, genital ulcerative diseases were predominant. Syphilis was the commonest STI. There was significant rise in the cases of syphilis, herpes progenitalis and genital warts and reduction in that of chancroid, lymphogranulomavenereum (LGV), donovanosis, candidiasis, trichomoniasis and bacterial vaginosis cases. The number of cases with primary syphilis diminished significantly (P<0.001), with a concomitant rise in secondary and early latent syphilis. A rising trend was observed in the HIV seropositivity during the different periods. The association of HIV seropositivity was consistently more in patients presenting with genital ulcers specially syphilis, and rose significantly from A (0.6%) to C (8.8%), but became stationary during D. A drastic change in the antimicrobial resistance of N. gonorrhoeae from B to C and C to D and the emergence of less sensitive isolates to ceftriaxone during the later part of the study were observed. INTERPRETATION & CONCLUSION: Our study showed a definite changing trend in the profile of STIs in the clinic attendees of a major STD centre during a 15 yr period. However, the significant rise in the cases of viral STIs and syphilis contrasted with reduction in the rest.

Massive posterior mitral annular calcification causing dynamic left ventricular outflow tract obstruction: mechanism and management implications.

We report a case of massive posterior mitral annular calcification causing severe systolic anterior motion of the anterior mitral leaflet and dynamic left ventricular outflow tract obstruction. Mechanism of genesis of systolic anterior motion by this unusual mechanism is illustrated. Importance of recognizing this mechanism and its implications for surgical therapy are discussed. Our patient also had liquefaction necrosis of mitral annular calcification causing its extension into left ventricular myocardium mimicking a tumor.