Revealing the Role of Solvent in anti-Oxypalladation-Triggered Regiocontrolled Domino Reactions for the Synthesis of Benzazepine- and Tetrahydroquinoline-Containing Scaffolds: A Combined Computational and Experimental Study.

Palladium-catalyzed regiocontrolled intramolecular oxypalladation-initiated cascades of multifunctional internal alkyne bearing an N-tosyl tether deliver functionalized benzazepine as an exclusive product via 6-endo-dig pathway in 1,4-dioxane solvent and tetrahydroquinoline scaffold as a major product via the 5-exo-dig pathway in the DMSO solvent. The role of the solvent in controlling the regioselectivity is still unknown which can be a major hurdle for further reaction development. Moreover, the reaction in DMSO suffered from having a mixture of products, and no exclusive formation of tetrahydroquinoline was achieved. Herein, we report a concerted computational and experimental study, revealing the role of the solvent in controlling the reaction outcome. DFT study revealed that the formation of the σ-vinylpalladium intermediate is reversible for the 5-exo-dig pathway while it is irreversible for the 6-endo-dig mechanism in 1,4-dioxane and consequently, the 5-exo-dig pathway is difficult to proceed. In contrast, both the 5-exo-dig and 6-endo-dig pathways are irreversible in DMSO. We predicted an exclusive formation of isobenzofuranone-fused chromane via the 5-exo-dig pathway when the N-tosyl tether is replaced by the O-tether in the internal alkyne in DMSO. The experimental study confirms the theoretical hypothesis and provides a highly chemo-divergent approach for the synthesis of biologically significant chromane with a large substrate scope and up to 95% yield at room temperature.

Capitalizing on strengths and minimizing weaknesses of veterans in civilian employment interviews: Perceptions of interviewers and veteran interviewees.

Like all job applicants, veterans have to face the ubiquitous employment interview and pass this potential hurdle to civilian sector employment. So, because of the uniqueness of transitioning from the military to civilian employment, the present paper sought to identify perceived interviewing strengths and weaknesses of veteran interviewees from (a) the perspective of civilian sector human resource professionals (i.e. hiring personnel) with experience interviewing veterans (Study 1, five focus groups, N = 14), and (b) veterans (Study 2, N = 93). Qualitative analysis of the focus group transcripts resulted in the emergence of two theme categories: (1) veteran interviewee strengths and (2) veteran interviewee weaknesses. This information guided the development of a 10-item survey that was completed by 93 veterans (Study 2). In its totality, the results (from both Study 1 and Study 2) indicated that communication of soft skills, confidence, and professionalism were perceived to be strengths that veterans displayed during civilian employment interviews, and conversely, the ineffective translation and communication of relevant technical skills acquired in the military, use of military jargon, and nervousness were considered to be weaknesses. Recommendations to capitalize on the strengths and mitigate the weaknesses are presented.

Reactivity and Mechanisms of Photoactivated Heterometallic [RuII NiII ] and [RuII NiII RuII ] Catalysts for Dihydrogen Generation from Water.

Two heterometallic photocatalysts were designed and probed for water reduction. Both [(bpy)2 RuII NiII (L1 )](ClO4 )2 (1) and [(bpy)2 RuII NiII (L2 )2 RuII (bpy)2 ](ClO4 )2 (2) can generate the low-valent precursor involved in hydride formation prior to dihydrogen generation. However, while the bimetallic [RuII NiII ] (1) requires the presence of an external photosensitizer to trigger catalytic activity, the trimetallic [RuII NiII RuII ] (2) displays significant coupling between the catalytic and light-harvesting units to promote intramolecular multielectron transfer and perform photocatalysis at the Ni center. A concerted experimental and theoretical effort proposes mechanisms to explain why 1 is unable to achieve self-supported catalysis, while 2 is fully photocatalytic.

Development of hierarchical magnesium oxide anchored cerium oxide nanocomposites with improved magnetic properties and photocatalytic performance.

A facile strategy was introduced for the development of pure MgO and its nanocomposites using different CeO2 contents (3%-7%) to enhance their magnetic properties and photocatalytic performance. Different morphologies (namely nanoflowers and rhombohedral type nanostructures) were obtained using an in situ hydrothermal method at different concentrations of CeO2. X-ray diffraction results revealed that peaks of CeO2 were observed along with peaks of MgO, which confirms the presence of both phases. The crystallite size and particle size were found to increase with changing CeO2 content in the host matrix of MgO. Moreover, the band gap reduces while the magnetic character increases with CeO2 content. The magnetic behaviour of the nanocomposites was elucidated on the basis of oxygen intrinsic defects, which are shown through XPS. EPR measurements were carried out to understand the valence electrons and establish the defects present in the material, which are related to the size of the nanostructures. The degradation of Rose Bengal dye was performed to probe the photocatalytic activity of the MgO@CeO2 nanocomposites. Hence the facile synthesis of these nanostructures conveyed good magnetic properties along with its application towards dye degradation.

Clinical significance of cathepsin L and cathepsin B in dilated cardiomyopathy.

Dysregulated expression of lysosomal cysteine cathepsins is associated with adverse cardiac remodeling, a characteristic of several cardiovascular diseases. However, the information regarding the role of cysteine cathepsin L (CTSL) and cathepsin B (CTSB) in dilated cardiomyopathy (DCM) is limited. The present study was aimed to investigate the expression of CTSL and CTSB in animal model of doxorubicin (doxo)-induced cardiomyopathy as well as in peripheral blood samples of DCM patients. Cardiac tissue sections from doxo-treated and control rats were used to study the expression of CTSL and CTSB by enzyme assay and immunohistochemistry (IHC). Peripheral blood mononuclear cells (PBMCs) isolated from DCM patients (n = 29) along with age-matched healthy controls (n = 28) were used to assay enzymatic activity of these cathepsins. Activities of these proteases were further correlated with echocardiographic parameters of DCM patients. A significant increase in CTSL activity and protein expression was observed with no changes in CTSB levels in doxo-treated rats as compared to controls. We also observed a drastic increase in the functional activity of cathepsin L+cathepsin B (CTSL+B), CTSL, and CTSB in DCM patients compared to controls (p ≤ 0.001). Increased levels of these proteases exhibited a statistically significant correlation with reduced left ventricular ejection fraction (LVEF) in DCM patients (ρ = -0.58, p = 0.01). For the first time, this study demonstrates a correlation between increased expression of CTSL and CTSB in PBMCs with severity of left ventricular dysfunction in DCM patients. Thus, these proteases may serve as blood-based biomarker of DCM and prove useful in its management.

5-HT2B receptor blockade attenuates ß-adrenergic receptor-stimulated myocardial remodeling in rats via inhibiting apoptosis: role of MAPKs and HSPs.

Recent studies have proposed the potential role of 5-HT2B receptor (5-HT2BR) blockade in alleviating myocardial dysfunction; hitherto, the regulatory pathway for its protective effect has remained enigmatic. In the present study, we sought to investigate the role of SB-204741, a 5-HT2BR blocker in isoproterenol-induced myocardial remodeling in rats and its cross-talk with apoptosis and mitogen activated protein kinase (MAPKs)/heat shock proteins (HSPs) pathway. To assess this hypothesis, we measured the effect of SB-204741 (0.25-1.0 mg/kg/day, i.p.) in isoproterenol (85 mg/kg/day, s.c.)-induced myocardial remodeling in rats. SB-204741 dose dependently improved hemodynamic and ventricular functions following isoproterenol-induced myocardial injury. This amelioration was well substantiated with reduced expression of 5-HT2B, inflammatory proteins (NF-κBp65, IKK-ß, TNF-α, IL-6, and Cox-2), MAPKs (p-p38/p38 and p-JNK/JNK ratio) accompanied with increased protein expression of HSPs (αB-crystallin, Hsp27 and Hsp70), autophagy (LC3 and Beclin-1) and p-ERK/ERK ratio. Additionally, SB-204741 inhibited apoptotic signaling pathway as there was decreased DAPI/TUNEL positivity and protein expression of cytochrome c, Bax, and caspase-3 along with increased Bcl-2 expression. Preservation of histopathological and ultrastructural components, normalization of nitric oxide level, endogenous antioxidants and myocyte injury marker enzymes were also observed. In conclusion, inhibition of apoptosis via modulation of MAPKs/HSPs is essential for 5-HT2BR blockade mediated cardioprotective effect.

Preclinical evidence for the pharmacological actions of naringin: a review.

Naringin, chemically 4',5,7- trihydroxyflavanone-7-rhamnoglucoside, is a major flavanone glycoside obtained from tomatoes, grapefruits, and many other citrus fruits. It has been experimentally documented to possess numerous biological properties such as antioxidant, anti-inflammatory, and antiapoptotic activities. In vitro and in vivo studies have further established the usefulness of naringin in various preclinical models of atherosclerosis, cardiovascular disorders, diabetes mellitus, neurodegenerative disorders, osteoporosis, and rheumatological disorders. Apart from this, naringin has also exerted chemopreventive and anticancer attributes in various models of oral, breast, colon, liver, lung, and ovarian cancer. This wide spectrum of biological expediency has been documented to be a result of either the upregulation of various cell survival proteins or the inhibition of inflammatory processes, or a combination of both. Due to the scarcity of human studies on naringin, this review focuses on the various established activities of naringin in in vitro and in vivo preclinical models, and its potential therapeutic applications using the available knowledge in the literature. Additionally, it also encompasses the pharmacokinetic properties of naringin and its inhibition of CYP isoenzymes, and the subsequent drug interactions. Moreover, further clinical research is evidently needed to provide significant insights into the mechanisms underlying the effects of naringin in humans.

Evaluating Diastolic Dysfunction as an Indicator of Cirrhotic Cardiomyopathy in Decompensated Chronic Liver Disease.

BACKGROUND: The clinical syndrome of cirrhotic cardiomyopathy (CCM) occurs quite frequently in decompensated chronic liver disease (DCLD) patients without any prior incidence. The compromised life expectancy under such conditions was the key that prompted us to conduct this study. PURPOSE: This study was planned to study the prevalence of diastolic dysfunction in chronic liver disease patients, to understand the diagnostic criteria of left ventricular diastolic dysfunction (LVDD) in cirrhotic patients, and to evaluate its occurrence as an early indicator of CCM. METHODS: A hospital-based, cross-sectional study was conducted on 158 patients, admitted to the Department of Medicine, Rajendra Institute of Medical Sciences, Ranchi, India, who conformed to our criteria for inclusion and exclusion. The study period was for 18 months. The subjects were clinically and radiologically diagnosed with chronic liver disease. Regression analysis for variables was performed to score the effects of potential variables with outcomes for diastolic dysfunction (DD) prediction. RESULTS: Out of 158 patients, 116 belonged to the age group of 31-60 years, pronouncing age to be a significant factor for LVDD. Fifty-three subjects had serum bilirubin levels >2mg/dL and we found serum bilirubin levels to bear a significant correlation with LVDD by exhibiting a p-value <0.0001. Both the Child-Turcotte-Pugh score class (p-value=0.0180) and QTc (p-value <0.0001) bear significant correlation with the development of LVDD, which is also evident from their area under the curve (AUC) values of 0.64 in the receiver operating characteristic (ROC) curve. CONCLUSION: Our study concludes that LVDD is an early indicator for assessing the severity of liver cirrhosis in DCLD. The correlation of DCLD with prolonged QTc could predispose patients with DCLD to ventricular arrhythmias. Hence, such patients should undergo serum bilirubin tests, and electrocardiographic checks at regular intervals for early detection, to increase their overall survival rates.

Highly stereoselective synthesis of α-glycosylated carboxylic acids by phenanthroline catalysis.

Carbohydrate molecules with an α-glycosylated carboxylic acid motif provide access to biologically relevant chemical space but are difficult to synthesize with high selectivity. To address this challenge, we report a mild and operationally simple protocol to synthesize a wide range of functionally and structurally diverse α-glycosylated carboxylic acids in good yields with high diastereoselectivity. Although there is no apparent correlation between reaction conversion and pK a of carboxylic acids, we found that carboxylic acids with a pK a of 4-5 provide high selectivity while those of a pK a of 2.5 or lower do not. Our strategy utilizes readily available 2,9-dibutyl-1,10-phenanthroline as an effective nucleophilic catalyst to displace a bromide leaving group from an activated sugar electrophile in a nucleophilic substitution reaction, forming phenanthrolinium intermediates. The attack of the carboxylic acid takes place from the α-face of the more reactive intermediate, resulting in the formation of α-glycosylated carboxylic acid. Previous calculations suggested that the hydroxyl group participates in the hydrogen bond interaction with the basic C2-oxygen of a sugar moiety and serves as a nucleophile to attack the C1-anomeric center. In contrast, our computational studies reveal that the carbonyl oxygen of the carboxylic acid serves as a nucleophile, with the carboxylic acid-OH forming a hydrogen bond with the basic C2-oxygen of the sugar moiety. This strong hydrogen bond (1.65 Å) interaction increases the nucleophilicity of the carbonyl oxygen of carboxylic acid and plays a critical role in the selectivity-determining step. In contrast, when alcohol acts as a nucleophile, this scenario is not possible since the -OH group of the alcohol interacts with the C2-oxygen and attacks the C1-anomeric carbon of the sugar moiety. This is also reflected in alcohol-OH's weak hydrogen bond (1.95 Å) interaction with the C2-oxygen. The O(C2)-HO (carboxylic acid) angle was measured to be 171° while the O(C2)-HO (alcohol) angle at 122° deviates from linearity, resulting in weak hydrogen bonding.

Estimating the Effect of Genital vs Extragenital Warts on Immunocompetent Indian Adult Patients; Quality of Life: A Comparative Cross-Sectional Study.

Introduction: Extragenital warts, often known as EGWs, affect between 7% and 10% of the population. Despite the plethora of research on the impact of genital warts (GWs) on "Quality Of Life", EGWs have received little attention. The purpose of this study was to conduct a cross-sectional investigation with the objective of contrasting the effects of GWs and EGWs on the health-related quality of life and other characteristics. Participants and Procedures: A cross-sectional clinical study was piloted at a tertiary care center. Participants in the study included two groups of healthy adults, each group consisting of 100 adult subjects. Those diagnosed with EGWs were included in group A, while patients diagnosed with GWs made up group B. The "Dermatology Life Quality Index" questionnaire was used to evaluate various parameters. Observations were compared for significance. Results: The majority of the subjects in both the groups were observed to have less than 10 warts. The Dermatology Life Quality Index score for the EGWs had an average of 8.66 ± 2.31 score; GWs had an average of 5.12 ± 3.25. This mean variance was statistically significant. The level of the dissatisfaction was highly significantly different among the groups and the subjects being more in the EGW group dissatisfied. Conclusion: The findings of this investigation indicate that EGWs have a significant and detrimental effect on the Quality Of Life. Medical experts must teach people how to prevent the disease's spread and recurrence due to its persistence. They must also consider the psychological and societal repercussions of the disease while discussing therapy choices.

Assessment of Right Ventricular Function by Strain Imaging in Patients Presenting with Acute Myocardial Infarction: An Original Research.

Objective: This study sought to determine the relationship between right ventricular (RV) function and clinical variables and prognosis in individuals with acute myocardial infarction (AMI) utilizing strain imaging. Materials and Methods: A prospective observational research involving 150 patients who had been admitted with AMI was carried out. Utilizing two-dimensional speckle-tracking strain imaging, RV function was assessed. Age, sex, risk factors, and comorbidities were recorded as clinical parameters. A 12-month follow-up was conducted to assess major adverse cardiovascular events (MACE). Results: 65% of the study's participants were men, with a mean age of 58.2 years. When compared to a healthy control group, individuals with AMI had significantly lower RV longitudinal strain (RVLS) (P 0.001). RVLS and left ventricular ejection fraction had a statistically significant connection (r = 0.642, P 0.001). Patients with compromised RVLS had a greater rate of MACE over the follow-up period compared to those with maintained RV function (P = 0.014). Conclusion: In conclusion, strain imaging offers useful information for evaluating RV function in patients with AMI. Reduced left ventricular performance and a higher likelihood of unfavorable clinical outcomes are linked to impaired RVLS. Utilizing strain imaging to detect RV dysfunction early can help direct treatment plans and enhance patient outcomes.

Pattern of Adverse Drug Reactions among Pregnant Women and Pediatric Patients in a Tertiary Care Hospital.

BACKGROUND: Adverse drug reactions (ADRs) among pregnant women and pediatric patients are a significant public health concern. ADRs monitoring and documentation are considered essential practices to decrease the chances of ADRs and ensure the safe use of drugs. OBJECTIVE: Therefore, the study was designed to evaluate the pattern of adverse drug reactions among pregnant women and pediatric patients in a tertiary care hospital. METHODS: The study was conducted at Kalpana Chawla Government Medical College and Hospital, Karnal, Haryana, for a period of 2 years. During this period, ADRs reported by the healthcare professionals of gynecology and pediatric department to the ADRs monitoring centre of our institute were included in the study. RESULTS: Out of 54 total ADRs, 40 ADRs occurred among pregnant women, and 14 ADRs were reported in pediatric patients. The majority of the ADRs were observed in the age group of 21-30 years (pregnant women) and 3-5 years (pediatric patients). Antibiotics were most commonly implicated in ADRs among pregnant women (60%) and pediatric patients (79%). In our study, the dermatological system was mostly affected among pregnant women and pediatric patients. Urticaria, contact dermatitis, and erythematous rash were the most commonly reported ADRs among pregnant women and pediatric patients. CONCLUSION: Over-prescribing and irrational use of antibiotics make these vulnerable populations more susceptible to ADRs and antibiotic resistance. Therefore, there is a need to create awareness among health care professionals regarding the spontaneous reporting of ADRs for ensuring drug safety and reducing morbidity and mortality among pregnant women and pediatric patients.

ZBTB12 is a molecular barrier to dedifferentiation in human pluripotent stem cells.

Development is generally viewed as one-way traffic of cell state transition from primitive to developmentally advanced states. However, molecular mechanisms that ensure the unidirectional transition of cell fates remain largely unknown. Through exact transcription start site mapping, we report an evolutionarily conserved BTB domain-containing zinc finger protein, ZBTB12, as a molecular barrier for dedifferentiation of human pluripotent stem cells (hPSCs). Single-cell RNA sequencing reveals that ZBTB12 is essential for three germ layer differentiation by blocking hPSC dedifferentiation. Mechanistically, ZBTB12 fine-tunes the expression of human endogenous retrovirus H (HERVH), a primate-specific retrotransposon, and targets specific transcripts that utilize HERVH as a regulatory element. In particular, the downregulation of HERVH-overlapping long non-coding RNAs (lncRNAs) by ZBTB12 is necessary for a successful exit from a pluripotent state and lineage derivation. Overall, we identify ZBTB12 as a molecular barrier that safeguards the unidirectional transition of metastable stem cell fates toward developmentally advanced states.

Andrographis paniculata extract protect against isoproterenol-induced myocardial injury by mitigating cardiac dysfunction and oxidative injury in rats.

Present study evaluated the cardioprotective effect of Andrographis paniculata (100, 200 or 400 mg/kg) against isoproterenol (85 mg/kg, b.w.)-induced cardiotoxicity referred as myocardial infarction in rats. Isoproterenol significantly (p < 0.05) decreased mean arterial pressure, heart rate, contractility and relaxation and increased left ventricular end diastolic pressure. Isoproterenol also significantly (p < 0.05) decreased antioxidants, superoxide dismutase, catalase, glutathione peroxidase, glutathione and increased leakage of cardiac injury markers; creatine phosphokinase-MB isoenzyme, lactate dehydrogenase concomitant to increased lipid peroxidation and histopathological perturbations. However, pretreatment with A. paniculata favorably restored hemodynamic parameters and left ventricular function and significantly (p < 0.05) prevented the depletion of endogenous antioxidants and myocyte marker enzymes as well as inhibited lipid peroxidation. Significant (p < 0.05) reversal of almost all the hemodynamic, biochemical and histopathological parameters by A. paniculata pretreatment in isoproterenol-induced cardiotoxicity depicted the cardioprotective effect of A. paniculata. Results showed that A. paniculata protected heart against cardiotoxic effects of isoproterenol by boosting endogenous antioxidant network, restoring ventricular function and maintaining structural integrity of heart.

Exploring the acceptance for e-learning among higher education students in India: combining technology acceptance model with external variables.

The concept of e-learning has now become fundamental in student learning process. This concept becomes even more relevant in situations of global crisis such as that arising from COVID-19. Since this pandemic there have been tectonic shifts in the education sector. Effective implementation of e-learning in higher education depends on students' adoption of this technology. So, this study aimed to identify the factors influencing the behavioral intentions and actual usage of students in adopting e-learning. Additionally, it also examined the mediation effects among different latent constructs. Based on technology acceptance model (TAM), an explanatory structural model of technology acceptance was tested along with introduction of three external variables. To do this, a quantitative investigation was conducted using an online survey of higher education students in India, obtaining 570 responses. The structural model was examined through the partial least square structural equation modeling. Results obtained make it possible to validate the proposed model as findings explains the 56.2% variance of actual usage. In addition, it shows the direct and indirect effect of all three selected external variables of personal innovativeness, social factors and self-efficacy on the main constructs of TAM. The findings of this study are relevant for the higher education management, administration, e-learning system developers, marketers and researchers for improving the effective usage of e-learning by developing more focused and customized learning solutions.

Assessment of cardiac function in children by strain imaging and its correlation with conventional echocardiographic parameter.

Background: The objectives of this study were to find out of normal reference value for age-dependent longitudinal strain values in children and find its correlation with conventional echocardiographic parameters. Methods: In total, 100 healthy normal children aged between 2 and 15 years were enrolled and divided into three age groups, namely, 2-5 years, 5-10 years, and 10-15 years. Using the GE Vivid 7 ultrasound platform with 4 or 7 MHz probes, both LV and RV global longitudinal strains and conventional echocardiographic parameters were acquired. Results: In normal healthy children, left ventricular GLS values were -20.10 to -19.68 (mean: -19.89), -21.93 to -21.02 (mean: -21.48), and -20.87 to -20.41 (mean: -20.64)) in children aged 2-5 years, 5-10 years, and 10-15 years and right ventricular GLS values were -16.80 to -16.44 (mean: -16.62), -27.85 to -27.27 (mean: -27.56), -28.44 to -27.93 (mean: -28.19) in the above three groups, respectively. No significant increase was noted in the left ventricular strain value from basal to the apical segment from age group 2 years to 15 years and no gender differences were seen. None of the conventional echocardiographic parameters commonly used to assess the left or right ventricular systolic function had a significant correlation with LVGLS and RVGLS. Conclusions: The mean LVGLS values were -19.89, -21.48, and -20.64 and RVGLS were -16.62, -27.56, and -28.19 in healthy normal children aged 2-5 years, 5-10 years, and 10-15 years, respectively, and conventional echocardiographic parameters did not have any significant correlation with these values.

Effect of Inula racemosa root extract on cardiac function and oxidative stress against isoproterenol-induced myocardial infarction.

The cardioprotective potential of Inula racemosa root hydroalcoholic extract against isoproterenol-induced myocardial infarction was investigated in rats. The rats treated with isoproterenol (85 mg/kg, s.c.) exhibited myocardial infarction, as evidenced by significant (P < 0.05) decrease in mean arterial pressure, heart rate, contractility, relaxation along with increased left ventricular end diastolic pressure, as well as decreased endogenous myocardial enzymatic and non-enzymatic antioxidants. Isoproterenol also significantly (P < 0.05) induced lipid peroxidation and increased leakage of myocyte injury marker enzymes. Pretreatment with I. racemosa extract (50, 100 or 200 mg/kg per day, p.o.) for 21 consecutive days, followed by isoproterenol injections on days 19th and 20th significantly (P < 0.05) improved cardiac function by increasing the heart rate, mean arterial pressure, contractility and relaxation along with decreasing left ventricular end diastolic pressure. Pretreatment with I. racemosa also significantly (P < 0.05) restored the reduced form of glutathione and endogenous antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase from the heart, which were depleted after isoproterenol administration. In addition to restoration of antioxidants, I. racemosa significantly (P < 0.05) inhibited lipid peroxidation and prevented the leakage of myocytes specific marker enzymes creatine phosphokinase-MB and lactate dehydrogenase from the heart. Thus, it is concluded that I. racemosa protects heart from isoproterenol-induced myocardial injury by reducing oxidative stress and modulating hemodynamic and ventricular functions of the heart. Present study findings demonstrate the cardioprotective effect of I. racemosa and support the pharmacological relevance of its use and cardioprotection mechanism in ischemic heart disease as well as substantiate its traditional claim.

Impact of Climatic Variations on Drug-induced Skin Reactions in Two Different Regions of India.

BACKGROUND: Around 2-3% of hospitalizations have been reported due to dermatological adverse drug reactions. Recent studies suggest that climatic variations affect the skin barrier function and extreme conditions aggravate skin disorders. OBJECTIVE: The present study was designed to compare the impact of climatic variations on drug-induced skin reactions in the Northern and Eastern regions of India. METHODS: We performed a one-year retrospective study to evaluate the impact of climatic variations (temperature and humidity) on drug-induced skin reactions in the Eastern (Kalyani, West Bengal) and Northern (Karnal, Haryana) regions. Drug-induced skin reactions were reported month-- wise in both the Eastern and Northern regions. Temperature and humidity levels were also noted month-wise in both regions. The direct correlation between climatic variations and the number of drug reactions were assessed using Pearson's correlation and quadratic regression analysis. RESULTS AND DISCUSSION: Overall, 99 and 81 dermatological adverse drug reactions were reported in tertiary care hospitals in the Northern and Eastern regions, respectively. During the summer season, the humidity level was found to be low in the Northern region as compared to the Eastern region. During this period, drug-induced skin reactions were reported significantly (p<0.05) more in the Northern region as compared to the Eastern region. Furthermore, quadratic regression analysis revealed that climatic variations contributed to drug reaction variability in the Northern region (68.5%) and Eastern region (23.5%). CONCLUSION: Therefore, the difference in the prevalence of drug-induced skin reactions may be related to the different climatic conditions among these two regions. Further studies in controlled climatic conditions should be performed for definitive correlations and to look into possible solutions.

Efficacy of Spironolactone in Adult Acne in Polycystic Ovary Syndrome Patients an Original Research.

INTRODUCTION: This prospective clinical trial was designed to assess the effects of a long-term therapy with spironolactone, with and without dietary-induced weight-loss, on clinical features, lipid profile, and insulin levels in women with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: Twenty-five patients (range of age 16-32 year; 13 lean and 12 overweight) fulfilling formal diagnostic criteria for PCOS (oligomenorrhea and/or amenorrhea, biochemical and/or clinical evidence of hyperadrogenism) were studied at baseline and then received oral spironolactone (100 mg/die) for 12 months; association with lifestyle modifications was recommended to all overweight patients. Clinical, endocrine, and metabolic parameters (oral glucose tolerance test [OGTT], lipid profile) were measured at baseline and at the end of the antiandrogen treatment. RESULTS: The therapy was associated with a significant average decline of triglycerides in overweight subjects and with increased high-density lipoprotein-cholesterol levels in lean patients. The insulin levels at 60 min during OGTT, homeostasis model assessment-insulin resistance and area under curve of insulin were significantly lowered in overweight women after 12 months of spironolactone and weight loss and no negative changes in insulin secretion and sensitivity were observed in PCOS women after pharmacological treatment alone. CONCLUSION: The efficacy of spironolactone on the androgenic clinical aspects of PCOS has been confirmed in this study. Furthermore, our data show that long-term treatment with spironolactone exerts no negative effects on lipoprotein profile and glucose metabolism; more relevant beneficial effects on glucose and lipid metabolism were observed when the antiandrogen was associated with weight loss in overweight PCOS women.