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Background: Raspberry ketone (RK), derived from red raspberry fruit ( Rubus idaeus, family Rosaceae), is a reported potent antiobesity agent. This study aims to investigate method development, validation, and in vitro and in vivo pharmacokinetics in rats. Materials & methods: LC–MS/MS was used to conduct method development, validation, stability, and oral PK samples of RK in plasma analyses. Results: RK was highly soluble in Tris buffer and stable in gastrointestinal fluids as well as plasma. Rat liver microsomal stability of RK in phase I and II studies was 84.96 ± 2.39 and 69.98 ± 8.69%, respectively, after 60 min. Intestinal permeability was 4.39 ± 1.37 × 10-5 cm/s. Maximal concentration was 1591.02 ± 64.76 ng/ml, which was achieved after 1 h (time to maximal concentration), and absolute oral bioavailability was 86.28%. Conclusion: Pharmacokinetic data serve as a keystone for preclinical and clinical adjuvant therapy.

Rotavirus is the leading cause of severe dehydrating gastroenteritis among children younger than 5 years in low-income and middle-income countries. Two vaccines-Rotavac and Rotasiil-are used in routine immunisation in India. The safety and immunogenicity of these vaccines administered in a mixed regimen is not documented. We therefore aimed to compare the safety and seroresponse of recipients of a mixed regimen versus a single regimen.We did a multicentre, open-label, randomised, controlled, phase 4, non-inferiority trial at two sites in India. We recruited healthy infants aged 6-8 weeks. Infants with systemic disorders, weight-for-height Z scores of less than minus three SDs, or a history of persistent diarrhoea were excluded. Eligible infants were randomly allocated to six groups in equal numbers to receive either the single vaccine regimen (ie, Rotavac-Rotavac-Rotavac [group 1] or Rotasiil-Rotasiil-Rotasiil [group 2]) or the mixed vaccine regimen (ie, Rotavac-Rotasiil-Rotavac [group 3], Rotasiil-Rotavac-Rotasiil [group 4], Rotavac-Rotasiil-Rotasiil [group 5], or Rotasiil-Rotavac-Rotavac [group 6]). Randomisation was done using an online software by site in blocks of at least 12. The primary outcome was seroresponse to rotavirus vaccine, measured using rotavirus-specific serum IgA antibodies 4 weeks after the third dose. The seroresponse rates were compared between recipients of the four mixed vaccine regimens (consisting of various combinations of Rotavac and Rotasiil) with recipients of the single vaccine regimens (consisting of Rotavac or Rotasiil only for all three doses). The non-inferiority margin was set at 10%. Safety follow-ups were done for the duration of study participation. This trial was registered with the Clinical Trials Registry India, number CTRI/2018/08/015317.Between March 25, 2019, and Jan 15, 2020, a total of 1979 eligible infants were randomly assigned to receive a single vaccine regimen (n=659; 329 in group 1 and 330 in group 2) or a mixed vaccine regimen (n=1320; 329 each in groups 3 and 4, and 331 each in groups 5 and 6). All eligible participants received the first dose, 1925 (97·3%) of 1979 received the second dose, and 1894 (95·7%) received all three doses of vaccine. 1852 (93·6%) of 1979 participants completed the follow-up. The immunogenicity analysis consisted of 1839 infants (1238 [67·3%] in the mixed vaccine regimen and 601 [32·7%] in the single vaccine regimen; 13 samples were insufficient in quantity) who completed vaccination and provided post-vaccination sera. The seroresponse rate in the mixed vaccine regimen group (33·5% [95% CI 30·9-36·2]) was non-inferior compared with the single vaccine regimen group (29·6% [26·1-33·4]); the seroresponse rate difference was 3·9% (95% CI -0·7 to 8·3). The proportion of participants with any type of solicited adverse events was 90·9% (95% CI 88·4-93·0) in the single vaccine regimen group and 91·1% (89·5-92·6) in the mixed vaccine regimen group. No vaccine-related serious adverse events or intussusception were reported during the study.Rotavac and Rotasiil can be safely used in an interchangeable manner for routine immunisation since the seroresponse was non-inferior in the mixed vaccine regimen compared with the single vaccine regimen. These results allow for flexibility in administering the vaccines, helping to overcome vaccine shortages and supply chain issues, and targeting migrant populations easily.Ministry of Health and Family Welfare, Government of India.For the Hindi translation of the abstract see Supplementary Materials section.

Abiraterone acetate (ABRTA) is clinically beneficial in management of metastatic castration-resistant prostate cancer (PC-3). With highlighted low solubility and permeability, orally hampered treatment of ABRTA necessitate high dose to achieve therapeutic efficacy. To triumph these challenges, we aimed to develop intestinal lymphatic transport facilitating lipid-based delivery to enhance bioavailability. ABRTA-containing self-nano emulsified drug delivery (ABRTA-SNEDDS) was statistically optimized by D-optimal design using design expert. Optimized formulation was characterized for particle size, thermodynamic stability

Background: Formononetin (FNT), a methoxy isoflavone, is a potential phytoconstituent utilized for refurbishing fractures in bone tissue. Conceding to its involvement in first-pass metabolism followed by glucuronidation, its absorption efficacy is limited. Hence, it belongs to the BCS class II classification. Background: Formononetin (FNT), a methoxy isoflavone, is a potential phytoconstituent utilized for refurbishing fractures in bone tissue. Conceding to its involvement in first-pass metabolism followed by glucuronidation, its absorption efficacy is limited. Hence, it belongs to the BCS class II classification. Objective: We designed the present work to enhance FNT oral bioavailability by using Phospholipids (PL) as a promising carrier. Formononetin Phospholipid Complex (FNT-PC) was prepared by the solvent evaporation method and characterized. Objective: We designed the present work to enhance FNT oral bioavailability by using Phospholipids (PL) as a promising carrier. Formononetin Phospholipid Complex (FNT-PC) was prepared by the solvent evaporation method and characterized. Method: FNT-PC was prepared by solvent evaporation method and characterization (FNT-PC) was performed using aqueous/n-octanol solubility and partition coefficient, FTIR, NMR, SEM, and in vivo pharmacokinetic study in female SD rats at 50mg/kg. Results: Physicochemical properties like aqueous/n-octanol solubility and partition coefficient were enhanced in FNT-PC. The FTIR spectrum confirmed there was no involvement of functional groups in the preparation of FNT-PC. Whereas, the NMR study resulted in the attachment of carbon (C-8) position of FNT by replacing the quaternary amine of PL to form FNT-PC. When scrutinized for its surface morphology, the FNT-PC exhibited the amorphous geometry that remarkably enhanced the dissolution of FNT (p Conclusion: To summarize, FNT-PC could substantially reduce the first-pass metabolism with enhanced free concentration, improving oral bioavailability for therapeutic use.

Background: The irrational use of antibiotics has led to the emergence of multi drug resistant pathogens. The phenomenon of MIC creeps occurs when organisms start showing raised MIC but within susceptible range giving an indication of the prevalence of rise in resistant pathogens in an area Methods: A cross sectional study in a large tertiary care hospital in North India to observe the susceptibility pattern among uropathogens and the possibility of MIC creeps. The Antimicrobial Susceptibility Testing (AST) and Minimum Inhibitory Concentration (MIC) were conducted by Vitek Compact 2. The identification of Extended Spectrum Beta Lactamase (ESBL) producers and Carbapenem Resistant Enterobacteriaceae (CRE) among Escherichia coli were noted. The MIC 50 and MIC 90 for Nitrofurantoin, the most widely used antibiotic for lower UTI, was calculated to investigate the phenomenon of MIC creep. Results: In our study, a total of 2522 urine samples were analyzed:1538 (61%) were positive with the commonest isolate being E. coli (n=736, 47.8%) followed by Klebsiella spp. (n=178, 11%). Less than 10% of resistance was observed for Fosfomycin, Amikacin, Nitrofurantoin, Imipenem, Meropenem and Colistin. ESBL producers and CRE E. coli were 528 (72% of 736) and 79 (11% of 736) respectively. Overall, 119/736 samples had an MIC ≥128. Amongst the ESBL producers, 96/528 had MIC ≥ 128 and amongst the CRE, 13/79 had MIC ≥ 128. Discussion: E. coli can be used to reflect the trends in development of resistance. In the current study, it was observed that E. coli showed a reduced susceptibility for Nitrofurantoin indicated by a creeping increase in MIC albeit within normal range. Conclusion: Trends in rising MIC should alert prescribers to use drugs such as Nitrofurantoin judiciously. Antimicrobial stewardship practices should be strongly implemented in hospitals to curb rising resistance and obtain better treatment outcomes for patients with infectious diseases.

'One drug- one target' to 'multiple drug- multiple targets' paradigm shifted to produce combination therapies, have found great outcomes to overcome multiple drug resistance (MDR). MDR is a significant barrier to the delivery of taxane-based anticancer medicines such as docetaxel, paclitaxel, and cabazitaxel. Due to MDR induced by drug efflux transporters, clinical application of these medications is impeded. To date, nanoformulations such as liposomes, micelles, polymeric nanoparticles, and gold nanoparticles have been investigated to deliver taxanes alone and in combination to reverse drug resistance. Despite the fact that various groups have already looked into taxane nano formulations in the literature, there isn't much in the way of polypharmacology and advanced nanoformulations with a focus on MDR. In this overview, we briefly covered the insights regarding MDR, difficulties related to current pharmaceutical products of taxanes, combination therapies of taxanes to combat MDR, all of which can be used to delve into cancer treatment.

Pancreastatin (PST), a chromogranin A (CHGA)-derived potent physiological dysglycemic peptide, regulates glucose/insulin homeostasis. We have identified a non-synonymous functional PST variant (p.Gly297Ser; rs9658664) that occurs in a large section of human populations. Association analysis of this single nucleotide polymorphism with cardiovascular/metabolic diseases states in Indian populations (n≈4300 subjects) displays elevated plasma glucose, glycosylated hemoglobin, diastolic blood pressure and catecholamines in Gly/Ser subjects as compared to wild-type individuals (Gly/Gly). Consistently, the 297Ser allele confers an increased risk (~1.3-1.6-fold) for type-2 diabetes/hypertension/coronary artery disease/metabolic syndrome. In corroboration, the variant peptide (PST-297S) displays gain-of-potency in several cellular events relevant for cardiometabolic disorders (e.g., increased expression of gluconeogenic genes, increased catecholamine secretion, greater inhibition of insulin-stimulated glucose-uptake) than the wild-type peptide (PST-WT). Computational docking analysis and molecular dynamics simulations show higher affinity binding of PST-297S peptide with glucose-regulated protein 78 (GRP78) and insulin receptor (IR) than PST-WT, providing a mechanistic basis for the enhanced activity of the variant peptide. In vitro binding assays validate these in silico predictions of PST peptides binding to GRP78 and IR. In conclusion, the PST 297Ser allele influences cardiovascular/metabolic phenotypes and emerges as a novel risk factor for type-2 diabetes/hypertension/coronary artery disease in human populations.

Pancreastatin (PST) is an endogenous bioactive peptide. PST is generated from chromogranin A (Chga) protein which is released by chromaffin and neuroendocrine cells. PST exhibits diabetogenic effect by antagonizing the action of insulin in adipocytes. The level of PST rises during obesity, resulting in persistent low-grade inflammation in adipocytes. Pancreastatin inhibitor 8 (PSTi8), which is developed by modification of PST sequence which antagonizes the action of PST. In this study, we investigated the immunometabolic effect of PSTi8 in the diet-induced obesity (DIO) model in C57BL/6 mice. Here we found PSTi8 decreased the body weight gain, fat mass and increased the lean mass in (DIO) mice. It also showed reduction of adipocyte hypertrophy in eWAT and lipid accumulation in liver of DIO mice. Immunoprofiling of stromal vascular fraction isolated from eWAT of PTSi8 treated mice showed increased anti-inflammatory M2 macrophages, Eosinophil, T-regulatory cells and reduced pro-inflammatory M1 macrophages, CD4 and CD8 T cell population. Apart from this, PSTi8 also improved the mitochondrial function by decreasing reactive oxygen species and increasing mitochondrial membrane potential, NADPH/NADP ratio and citrate synthase activity in eWAT of DIO mice. It also increased the protein expression of pAMPK, pAKT, Arginase -1 and decreased the expression of MHC-II and iNOS in eWAT of DIO mice. In conclusion, PSTi8 exerted its beneficial effect on restoring energy expenditure by reducing adipose tissue inflammation.

Background India bears a high burden of both dengue and malaria. An early distinction between the two could be invaluable in reducing mortality and morbidity. The objective of this study is to identify clinical, biochemical, and radiological parameters for the same, which could aid early detection and treatment of both diseases. Methods A cross-sectional study was conducted at a tertiary care hospital in South Delhi, India. 100 pre-diagnosed patients each of dengue and malaria were studied. Features on clinical examination, and results of radiological and biochemical investigations were recorded. Continuous variables were compared using t-test, whereas categorical variables were subjected to chi-square test. P-value of ≤0.05 was taken as significant. Results All patients presented with short pyrexia (fever Conclusion The study concludes that a distinction between dengue and malaria can be made on the basis of their clinical, radiological and biochemical findings.

Splenic infarction is encountered rarely in clinical practice. The wide spectrum of clinical presentation makes its diagnosis elusive. It usually responds to conservative management but rarely surgical intervention is needed if it is refractory symptoms or secondary complication. We present our experience of splenectomy performed for splenic infarct which failed to respond to medical management over the last 5 years from 2015 to 2019. We performed 9 splenectomies (7 laparoscopic and 2 open). Most of these patients were young females (66.7%, 6/9). Mean age of patients in our series was 31.1 years (± 15.8 years). Fever (77.8%) and abdominal pain (66.7%) were the most common presenting symptoms. Diagnosis was made on the basis of contrast-enhanced CT scan of abdomen. Infective endocarditis (33.3%, 3/9) was the most common underlying aetiology. All of these patients initially received a trial of conservative management for a median duration of 19 days. Post-operative course was uneventful for most of these patients with a resolution of symptoms in post-operative period. There were two patients who developed surgical site infection and one who developed subdiaphragmatic collection which was drained percutaneously via a pigtail insertion. Patients were discharged after a median duration of 4 days after surgery and referred for post-splenectomy vaccination in haematology clinic. There is scarcity of literature on role of surgical intervention in symptomatic splenic infarct refractory to conservative management. How long should these patients be managed before considering them for splenectomy is a question worth exploring.

The dermatophytes are a group of filamentous fungi that infect only superficial keratinized tissues of skin, hair and nails. KOH mount is an easy and rapid method to detect them. It is generally not difficult to make a diagnosis of dermatophytes on KOH based on typical characteristic appearance. However, sometimes the diagnosis becomes a challenge because of numerous normal structures which can be very similar to dermatophytes, especially when scrapings are taken from already treated modified tinea infection. This may lead to an erroneous diagnosis and inappropriate treatment of the patient with antifungal drugs which have their own side effects. In the present article, numerous mimickers of dermatophytes on KOH are described with the purpose of avoiding the potential diagnostic pitfalls. Keywords: Mimickers, Dermatophytes, KOH, Tinea.

Introduction: Majority of lung cancer presents at an advanced unresectable stage, emphasizing the diagnosis on cytological specimens like EBUS-TBNA. This study was aimed to subtype lung carcinomas on EBUS-TBNA specimens on smears and cell blocks (CB) and to assess the utility of limited panel ICC towards this subtyping. Materials and Methods: This is both retrospective and prospective study done on total of 142 cases for two and half years. The samples from either lung or mediastinal lymph nodes diagnosed as lung carcinoma on cytomorphology in correlation with clinico – radiological features were included. Extrapulmonary metastatic tumors, lymphomas and malignancies other than carcinomas were excluded. The cytologic material (EBUS-TBNA smears and CB) was obtained by EBUS TBNA procedure done on lung lesions and/or mediastinal lymph nodes and stained with required stains. All cases were first classified as small cell carcinoma (SCC) and non small cell carcinoma (NSCC) on cytomorphology as per 2004 WHO classification. NSCC was then further subtyped. ICC with TTF1/p63 antibodies was applied on NSCC and synaptophysin on SCC/neuroendocrine tumors. Napsin A was applied on p63/TTF1 negative cases. The results were expressed in frequencies and percentages. Result: On cytomorphology alone, 25 of 142 cases (17.6%) were classified as SCC and 117 cases (82.4%) as NSCC. NSCC was further subtyped on cytomorphology (smears+CB) into definitive (squamous cell carcinoma [SqCC]/adenocarcinoma [ADC]) v/s favouring (favouring SqCC/ ADC/ adenosquamous carcinoma) v/s not otherwise specified (NOS) in 41 (35.1%) v/s 33(28.2%) v/s 43(36.7%) cases respectively. Immunostains TTF1/ p63 and napsin A applied on possible 86 NSCC cases reduced NOS to 9.3 %. Synaptophysin confirmed all 20 cases of SCC and 1 large cell neuroendocrine carcinoma (LCNC). Overall in 142 cases, limited panel ICC reduced NSCC-NOS to 11.9%. Conclusion: Subtyping of lung carcinoma on EBUS- TBNA samples is feasible. Preparat

Cassia occidentalis L. stem extract is used as a purgative, febrifuge, and diuretic, and in the treatment of flu, fever, fracture and bone diseases. Pharmacological studies prove the osteogenic and antiresorptive effects of Cassia occidentalis L. ethanolic extract (COEE), which may be due to apigenin, apigenin-6-C-glucopyranoside, luteolin, 3′,4′,7-trihydroxyflavone and emodin. The objectives of this study was to develop a selective and sensitive LC-MS/MS method and validate for the simultaneous determination of the above five biomarkers in rat plasma after oral administration of COEE at a dose of 500 mg kg−1. The analytes were separated on a Phenomenex Luna C18 column (4.6 × 150 mm, 3.0 μm) with an isocratic mobile phase consisting of methanol-10 mM ammonium acetate buffer (95 : 05, v/v). Run time was for 5.5 min with LLOQ of 1 ng mL−1 for all the analytes. The mass spectrometer was operating in negative ionization mode for quantification of the analytes. The calibration curves were linear (r2 > 0.99) for all the analytes. The intra- and inter-day precisions were less than 8.17% and the relative error was between −8.57% and 7.28%. Analytes were rapidly absorbed in the oral pharmacokinetic study. The biomarkers were stable in simulated gastric and intestinal fluids but underwent metabolism in rat liver microsomes. This is the first report on in vivo oral pharmacokinetics and in vitro stability studies of osteogenic compounds present in COEE. These results will be helpful for further understanding of pharmacodynamic behaviour of COEE and the bioanalytical method will be useful for further preclinical/clinical trials.

Background: Access to health-care facilities and essential medicines still remains a worldwide problem, particularly in developing countries. Greater awareness among health-care professional regarding generic drugs may translate into the increased consumption of generic drugs and reduction in healthcare costs wild maintaining the safety efficacy and quality off health-care system. Aim and Objectives: This study was conducted to analyze the knowledge and perception of generic medicines among MBBS and Nursing students in a medical teaching institute. Materials and Methods: A questionnaire-based cross-sectional study was conducted among 260 students (172 MBBS, 88 Nursing course) in Government Medical College Jalgaon, to assess knowledge and attitude of students for generic medicines. Descriptive statistics and Kruskal–Wallis test were used to analyze the responses. Results: Most respondents from MBBS (86%) and nursing course (89%) agree to need more information about how bioequivalence test are conducted for generic medicine. Perception about branded medicines requiring high quality standards as compared to generic medicines was high in both courses’ students with 69.3% of nursing students and 43.6% of MBBS students having wrong perception. About 77.4% of MBBS students and 42% of nursing students responded positively to the statement about generic medicines being cheaper than branded drugs. Conclusion: Students from both the courses showed eagerness to have more information, were lacking in the knowledge, and had confused attitude toward generic medicines. Proper education and training may impart proper knowledge and change the attitude among students toward the generic medicines.

Rhino-orbital mycosis has been recently recognised as one of the sequelae in COVID-19 recovered patients. In India, detection of mucormycosis is declared as notifiable disease. In this article, the authors aim to describe the characteristics of patients presenting with post covid fungal infection which could be detected on 10% potassium hydroxide (KOH) wet mount and Giemsa stain put on crush biopsy smear. We describe 10 COVID-19 recovered patients admitted to ENT department of the hospital during second wave of COVID-19 infection. They presented with post covid fungal sinusitis and ophthalmic complications and planned for surgery. KOH mount and Giemsa stain were used for possible opinion and confirmed by culture. The observations were described in mean and percentages. All ten (100%) COVID-19 recovered patients were previously diagnosed with type 2 diabetes mellitus (DM) for 2-11 years. All 10 patients (100%) were given oral or intravenous corticosteroids for mean of 21 days (3 weeks-till presentation to ENT department). Simple procedures with 10% KOH mount and Giemsa stain could detect fungal hypae in all the cases and could provide possible opinion in 9 of 10 (90%) cases for timely management of the patients. The authors hypothesize that uncontrolled DM and prolonged use of corticosteroids may act as culprits of rhino-orbital mycosis in COVID-19 recovered patients. Simple and routine 10% KOH mount and Giemsa stain may provide early opinion of fungal hypae to ensure quick management and survival of the patients.

Background: Radiocontrast media are used extensively nowadays to visualize internal organs. Currently, non-ionic iodinated contrast media are used which are generally considered to be safe but some adverse reactions have been reported. Thus, the present study was carried out to analyze the nature and incidence of adverse drug reactions (ADRs) to radiographic contrast media in a teaching hospital. Methods:An observational study carried out for a period of six months in a teaching hospital. Contrast media induced adverse reactions were analyzed in terms of affected organs, rate, causality assessment, severity and preventability. The treatment and outcomes of adverse events were also recorded. Naranjo Probability Scale was used to evaluate the relationship between the contrast agent used and the suspected ADR. The severity of the suspected ADRs was determined using Hartwig Scale and preventability was assessed using modified Schumock and Thornton criterion. Results:A total of 15 suspected ADRs occurred in 11 patients with an incidence of 1.4%. It included 5 (45.4%) males and 6 (54.5%) females (p < 05). The highest percentage (72.7 %) of ADRs was seen in adult patients, the mean age being 40.8 years. Vomiting (33.3%) was the most common ADR noted followed by severe nausea and rashes. 64.7 % of ADRs were categorized as probable and 35.3 % were possible. Adverse reactions required treatment in 46.6% patients. There was no fatality reported. Conclusion:The reactions observed were mild to moderate in severity and occurred within 30 minutes of the administration of the contrast.

Introduction Arteriovenous fistula is considered as a lifeline for chronic kidney patients undergoing maintenance hemodialysis. Objective To study the outcome of ligation of the accessory vein causing hyperperfusion and ischemia of the ipsilateral limb. Method ology: A single institution, single surgeon, in-hospital, retrospective case series of patients presented with alarm symptoms in postoperative period following arteriovenous fistula. Results A total of 800 AVF were created between 2016 and 2019, out of which 6/800 (0.75 %) patients presented with alarm symptoms related to venous hypertension and underwent accessory vein ligation. All showed normal recovery with complete resolution of symptoms postoperatively. Conclusion Timely ligation of the accessory vein in patients with arteriovenous fistula with accessory vein related alarm symptoms showed salvage of lifeline and limb with no residual complications during follow-up., Highlights • It is important to keep a close follow-up so that timely intervention could be performed. • Hyperperfusion due to accessory vein leading to massive edema, reduced or loss of motor function of digits and venous ischemia is neglected cause of concern associated with AVF. • Timely ligation of the accessory vein in patients with alarm symptoms showed salvage of lifeline and limb. • Venous ischemia is under-reported and is a cause of litigation and compensation.

Advancement in biotechnology provided a notable expansion of peptide and protein therapeutics, used as antigens, vaccines, hormones. It has a prodigious potential to treat a broad spectrum of diseases such as cancer, metabolic disorders, bone disorders, and so forth. Protein and peptide therapeutics are administered parenterally due to their poor bioavailability and stability, restricting their use. Hence, research focuses on the oral delivery of peptides and proteins for the ease of self-administration. In the present review, we first address the main obstacles in the oral delivery system in addition to approaches used to enhance the stability and bioavailability of peptide/protein. We describe the physiochemical parameters of the peptides and proteins influencing bioavailability in the systemic circulation. It encounters, many barriers affecting its stability, such as poor cellular membrane permeability at the GIT site, enzymatic degradation (various proteases), and first-pass hepatic metabolism. Then describe the current approaches to overcome the challenges mentioned above by the use of absorption enhancers or carriers, structural modification, formulation and advance technology.

Obesity and associated metabolic disorders are heading up with an alarming rate in developing nations. One of highly sought solution for metabolic disorders is to identify natural molecule with an ability to reduce obesity and increase insulin sensitivity. Coelogin (CLN) is a phenanthrene derivative isolated from the ethanolic extract of Coelogyne cristata. In our constant efforts to identify novel anti-dyslipidemic and anti-adipogenic compounds using CFPMA (common feature pharmacophore model using known anti-adipogenic compounds) model, predicted possible anti-adipogenic activity of CLN. In vitro results showed significant inhibition of adipogenesis in 3T3-L1 and C3H10T1/2 cell by CLN. It arrests the cell cycle in G1 phase of interphase and inhibits mitotic clonal expansion to regulate adipogenesis. CLN elicits insulin sensitizing effect in mature adipocytes. During extracellular flux assessment studies, it increases oxidative respiration and energy expenditure in adipocytes. In vivo, CLN reversed HFD-induced dyslipidemia as well as insulin resistance in C57BL/6 mice. It promoted the expression of genes involved in improved mitochondrial function and fatty acid oxidation in eWAT. CLN restored energy expenditure and increased the capacity of energy utilization in HFD fed mice. Taken together, the study indicated beneficial effects of CLN in combating obesity-associated metabolic complications.

Objectives Hyperglycemia-induced SIRT1, DNMT1, SODs, as well as oxidative stress, play a pivotal role in the progression of diabetic nephropathy. Cissus quadrangularis, holds antioxidant and hypoglycemic activity; however, a direct link between its activity and prevention of diabetic nephropathy has not been ascertained yet. Accordingly, we aimed to delineate the protective effect of ethanolic extract of Cissus quadrangularis (EECQ) against high-fat diet/streptozotocin (HFD/STZ) induced diabetic nephropathy rats. Methods The control group was fed with a normal chow diet. Rats kept on an HFD for 12 weeks with a single low dose of STZ manifested the features of diabetic nephropathy. The treatment was done by the oral administration of EECQ (200 mg/kg) for six weeks (six rats in each group). Key findings Treatment with EECQ demonstrated substantial attenuation of elevated insulin resistance, lipid profile and creatinine level. Additionally, EECQ restored albuminuria, glomerular filtration rate and creatinine clearance in diabetic nephropathy rats. Furthermore, HFD consumption in rats culminated in reduced SIRT1 and enhanced DNMT1 expression, nonetheless, rescued by EECQ. Moreover, EECQ augmented the SOD 1 and 3 levels, thereby safeguarded from oxidative damage and renal inflammation. Besides, treatment protected from renal fibrosis by downregulating TGFβ, Smad2/3 and col1/3 expression in diseased rats. Conclusions Thus, based on the above findings, we conclude that EECQ shows a protective effect against diabetic nephropathy.

Metabolic Syndrome is a multifactorial disease associated with increased risk of cardiovascular disorders, type 2 diabetes mellitus, fatty liver disease, etc. Various stress stimuli such as reactive oxygen species, endoplasmic reticulum stress, mitochondrial dysfunction, increased cytokines, or free fatty acids are known to aggravate progressive development of hyperglycemia and hyperlipidemia. Although the exact mechanism contributing to altered metabolism is unclear. Evidence suggests stress kinase role to be a crucial one in metabolic syndrome. Stress kinase, c-jun N-terminal kinase activation (JNK) is involved in various metabolic manifestations including obesity, insulin resistance, fatty liver disease as well as cardiometabolic disorders. It emerged as a foremost mediator in regulating metabolism in the liver, skeletal muscle, adipose tissue as well as pancreatic β cells. It has three isoforms each having a unique and tissue-specific role in altered metabolism. Current findings based on genetic manipulation or chemical inhibition studies identified JNK isoforms to play a central role in the regulation of whole-body metabolism, suggesting it to be a novel therapeutic target. Hence, it is imperative to elucidate its role in metabolic syndrome onset and progression. The purpose of this review is to elucidate in vitro and in vivo implications of JNK signaling along with the therapeutic strategy to inhibit specific isoform. Since metabolic syndrome is an array of diseases and complex pathway, carefully examining each tissue will be important for specific treatment strategies.

Aims Hepatic steatosis in women confronting menopause is the manifestation of substantial fructose consumption and forms a positive feedback loop to develop endoplasmic reticulum (ER) stress. Previously pancreastatin inhibitor peptide-8 (PSTi8) and Metformin (Met) combination effectively ameliorated hepatic lipid accumulation in high fructose diet (HFrD) fed diabetic mice models at reduced doses. Moreover, SIRT-1 plays a crucial role in the regulation of SREBP-1c. Hence we hypothesized that Met and PSTi8 in combination (at therapeutic lower doses) could mitigate hepatic steatosis linked ER stress by activating SIRT-1 and precluding SREBP-1c in HFrD fed 4-Vinylcyclohexenediepoxide (HVCD) induced perimenopausal rats. Main methods HVCD rats were fed HFrD for 12 weeks, accompanied by 14 days of treatment with Met, PSTi8, and combination. We confirmed model establishment by estrus cycle study, estradiol level, and intraperitoneal glucose tolerance test. Plasma lipid profile and liver function were determined. Also, mRNA and protein expressions were examined. Moreover, distribution of SIRT-1 and SREBP-1c was detected in HepG2 cells by immunofluorescence staining. Key findings HVCD group displayed augmented insulin resistance (IR), lipogenesis, and ER stress in the liver. Combination therapy improved the estrus cyclicity, estradiol, and lipid profile of HVCD rats. Met and PSTi8 combination reduced hepatic SREBP-1c and triggered SIRT-1 expression in high fructose-induced insulin-resistant HepG2 cells; consequently, combination therapy attenuated ER stress. Significance Succinctly, present research promotes impetus concerning the remedial impact of Met with PSTi8 at lower therapeutic doses to ameliorate hepatic IR, steatosis, and associated ER stress by revamping the SIRT-1/SREBP-1c axis in perimenopausal rats., Combination therapy (Met + PSTi8); PSTi8; Metformin; Hepatic steatosis; ER stress; SIRT-1; SREBP-1c; Perimenopausal rat

Ebola virus disease first appeared in 1976 in Zaire (now democratic republic of Congo). Since then virus outbreaks occurred periodically in African countries. The cases notified in March 2014 in west Africa was largest outbreak till now. In 2020 there is ongoing outbreak of Zaire Ebola virus in democratic republic of Congo. Ebola virus is single stranded RNA virus which causes viral hemorrhagic fever in humans presenting as high fever, chills, loss of appetite, myalgia, headache. Till now there was no specific treatment, symptomatic treatment methods including infusion of electrolyte and/or antibiotics were mainly used. In October 2020 FDA approved the first treatment for Zaire Ebola virus disease in adult and pediatric patients, including neonates born to a mother who is RT-PCR positive for Zaire ebolavirus infection. The treatment is called Inmazeb, combination of three recombinant human IgG1κ monoclonal antibodies (Atoltivimab, Maftivimab, and Odesivimab-ebgn) each targeting the Zaire ebolavirus glycoprotein.

In the preceding study, we delineated that high-fat diet (HFD) consumption in mice increases the circulatory level of pancreastatin (PST), which additionally enhances the free fatty acid (FFA) concentration in circulation. Consequently, the aggravated FFA activates Fetuin-A, which facilitates hepatic lipid accumulation, insulin resistance (IR), and culminates in type 2 diabetes (T2D). Metformin (Met) is a widely known first-line drug for the treatment of T2D. We previously unveiled PSTi8, an inhibitor of PST, comprising antidiabetic property. Hence, we hypothesized that combination therapy of Met and PSTi8, at reduced therapeutic doses, would mitigate HFD-induced IR by inhibiting hepatic Fetuin-A in mice model of T2D. C57BL/6 mice were fed HFD for 12 weeks, followed by treatment with Met, PSTi8, and its combination for 10 days. Glucose and insulin tolerance tests were conducted. Circulatory levels of PST, Fetuin-A, and lipid markers were determined. Also, the mRNA and protein expression of Fetuin-A was assessed by qPCR, western blotting, and immunofluorescence. Moreover, the energy expenditure was measured by comprehensive laboratory animal monitoring system (CLAMS). Combination therapy displayed improved PST, Fetuin-A, and lipid profile in plasma. We also found reduced hepatic Fetuin-A, which reduced inhibitory phosphorylation of IRS and increased phosphorylation of AKT. Consequently, ameliorated hepatic lipogenesis, gluconeogenesis, and inflammation. Also, combination treatment attenuated Fetuin-A expression, lipid accumulation, and glucose production in palmitate-induced HepG2 cells. Altogether current study promulgates the beneficial effect of combination therapy of Met and PSTi8 (comparable to alone higher therapeutic doses) to ameliorate Fetuin-A activation, hepatic lipid accumulation, insulin resistance, and associated progressive pathophysiological alterations in T2D., Diabetes; Fetuin-A; Combination therapy; PSTi8; Metformin; Insulin resistance; Biotechnology; Biochemistry; Molecular biology; Pharmacology; Endocrinology; Metabolism; Metabolic disorder; Pharmaceutical science.

The Indian general elections (Lok Sabha Elections) is billed as the ‘country’s biggest festival.’ India is the second most populous country in the world with around 900 million eligible voters in the year 2019. Making sure that all eligible voters poll their votes securely is difficult to do in a single day. Therefore, the election event in India lasts for several weeks. It has been evident that the general elections bring about uncertainty in the economy while stock prices are considered to be sensitive to all new information and prevailing uncertainties. This paper, therefore, intends to study the impact of Indian General Elections on the stock market performances of the firms. This study uses the election event data of 2004, 2009 and 2014 as the sample. Fixed Effect (FE) model, Random effect (RE) model, difference-in-difference (DID) and a triple difference-in-difference methods are preformed to estimate the effect of general election event on the stock market performances of the firms, measured by market capitalization of the firms and their stock returns.

Free fatty acid-mediated obesity plays a crucial role in the pathogenesis of Type 2 Diabetes. FFA induced JNK activation acts as a central regulator in causing hepatic insulin resistance. Similarly, Pancreastatin, a chromogranin A peptide, serves as a crucial link between FFA-induced insulin resistance. Therefore, in the present work, we sought to test Pancreastatin inhibitor PSTi8 to ameliorate FFA-induced hepatic insulin resistance in in vitro and in vivo models.To verify our objective, we exposed hepatocytes (HepG2 cells) with palmitate (0.3 mM) or palmitate + PSTi8 (200 nM). Parallelly mice were fed either HFD or HFD + PSTi8 (1 mg/kg). After 21 days animals were scanned for increased fat mass, along with GTT, ITT and PTT experiment to check glucose, and insulin tolerance. Furthermore, ROS generation and hepatic glycogen content was measured in FFA exposed hepatocytes. Gene expression and protein expression studies were further conducted to delineate the action mechanism of PSTi8.PSTi8 exposure decreased ROS accumulation, lipid accumulation, and reduced glycogen content in FFA-induced groups. It also enhances glucose uptake and reduces gluconeogenesis to combat the FFA effect. Furthermore, gene expression studies indicate that PSTi8 treatment reduces NADPH oxidase3 (NOX3) expression and inhibits JNK signaling, a predominant source of ROS-induced insulin resistance.To summarize, the protective effect of PSTi8 on FFA-induced insulin resistance is mediated via inhibition of JNK signaling, which leads to decreased ROS generation and enhanced insulin sensitivity. Hence PSTi8 could be a therapeutic molecule to prevent western diet-induced insulin resistance.

Pancreastatin (PST), a chromogranin A (CHGA) derived peptide connects obesity with insulin resistance by inducing inflammation. Previously, we have evaluated potential activity of PST inhibitor (PSTi8) in liver and adipose tissue in type 2 diabetic mice model. In this study we further explore the therapeutic effect of PSTi8 on glucose metabolism in skeletal muscle cells/tissue and its effect on energy homeostasis in diet induced diabetic mice model. In in-vitro studies, we found that PSTi8 increases glucose uptake via enhanced GLUT4 translocation in L6 cells. This positive effect of PSTi8 led us to proceed with in-vivo studies in diabetic mice. C57BL/6 mice were fed HFD or HFrD diet for 12 weeks along with single STZ induction at 4th week followed by PSTi8 treatment. We found that HFD and HFrD model showed increased fat mass, caused glucose intolerance and insulin resistance, with accompanying proinflammatory effect on epididymal white adipose tissue (eWAT) together leading to skeletal muscle insulin resistance. Administration of PSTi8 protects from diet induced inflammatory response and enhances glucose tolerance and insulin sensitivity. PSTi8 improves circulating adipokine and lipid parameters, along with switch in macrophage polarisation from M1 to M2 in stromal vascular fraction of adipose tissue. In addition, treatment of PSTi8 also improves energy homeostasis, decreases circulatory non-esterified fatty acids level and inhibits ceramide deposition in muscle tissue. Overall this increased muscle insulin sensitivity is mediated via AKT/AS160/GLUT4 pathway activation. Our results reveal that PSTi8 inhibits the obesity mediated inflammation which enhances glucose disposal in skeletal muscle.

Introduction Primary amenorrhea is a challenging entity as it affects the reproductive outcome. Primary amenorrhea is an absence of secondary sexual characters until 14 years of age or absence of menstruation with secondary sexual characters until 16 years of age. Aim The aim of this article is to study the frequency, etiologic causes, presentation, diagnosis, and optimal mode of management of primary amenorrhea. Materials and methods All girls who had not attained menarche until 16 years of age in the absence of secondary sexual characters and until 14 years, if no secondary sexual characters, and were willing for follow-up were subjected to investigations and were treated as per the etiology. Results Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome was the most common cause of primary amenorrhea (42.85%) followed by imperforate hymen (28.57%) and transverse vaginal septum (21.42%), one each of low, mid, and high varieties. There was one case of androgen insensitivity syndrome. Conclusion Establishing correct diagnosis is essential for planning treatment and management strategies in primary amenorrhea as treatment goals are preservation of fertility and progression of normal development. How to cite this article Bhalerao AV, Garg R. Müllerian Anomalies: A Cause for Primary Amenorrhea. J South Asian Feder Obst Gynae 2017;9(3):221-224.

Background Pelvic organ prolapse (POP) is a common health problem affecting 40% multiparous women above 35 years of age. Lifetime risk of women requiring surgery for recurrence is 10%. The POP is intricious due to complex pelvic anatomy, and difficulty increases due to tissue weakness, lack of evidence-based surgical guidelines, and lack of standardized definition for surgical success, which results in highly variable estimates of success. Aim To compare the effectiveness of traditional anteroposterior repair with site-specific repair with concomitant vaginal hysterectomy with respect to anatomical considerations by POP-Q and functional or symptomatic considerations, complications, duration of surgery, and recurrence. Materials and methods This hospital-based randomized controlled trial was carried out at a tertiary care hospital from January 1, 2013 to December 31, 2015 over a period of 3 years after obtaining ethical committee approval. All women attending the gynecological outpatient department having symptoms of mass coming out of vagina were subjected to detailed history and examination and 51 women underwent traditional anterior and posterior repair and 44 women underwent site-specific repair with concomitant hysterectomy, with random sampling according to computerized sheet. The effectiveness of both the surgeries was assessed and compared. Observations There was statistically significant improvement in all the sites of POP-Q points using traditional repair and site-specific repair. When compared, site-specific repair by POP-Q was better than traditional method. Conclusion Site-specific repair of decussated natural tissue has great curative potential, and success is attributable to site-specific repair, rather than nonspecific scar formation by traditional method. Thus, it is important to properly quantify the repair to be done, whether anterior or posterior, and perform site-specific repair. How to cite this article Bhalerao AV, Vora A, Bhalerao K, Garg R. To Compare the Effectiveness of Traditional Anterior Colporrhaphy, Posterior Colpoperineorrhaphy with Site-specific Anterior and Posterior Repair for Pelvic Organ Prolapse. J South Asian Feder Menopause Soc 2017;5(2):92-98.

The aim of this study was to evaluate and compare the efficacy and safety of serratiopeptidase and aceclofenac in reducing swelling and pain following soft tissue injury. This study included 100 patients with soft tissue injury to upper limb, lower limb or both. They were randomly divided into two groups of 50 each to receive serratiopeptidase and aceclofenac. Evaluation of efficacy was made using tape measurement (for swelling), and visual analogue scale (for pain) on day 0, week 1and week 2. Serratiopeptidase showed significant anti-inflammatory effect and mild analgesic effect. None of the patient was required to be put on another analgesic or any alteration in treatment. Aceclofenac showed superior analgesic effect as compared to serratiopeptidase. Mild to moderate adverse effects were reported. The most common adverse effect reported was dyspepsia. All were mild and did not require any alteration or discontinuation of treatment.

Introduction Vaginal vault prolapse can be prevented by supporting the vaginal cuff, which is an essential part of hysterectomy, whether done abdominally or vaginally. The American Association of Gynecologic Laparoscopists (AAGL) has recommended for future research, specifically, a randomized trial comparing McCall's culdoplasty (with uterosacral ligament plication) with vaginal high uterosacral ligament suspension (HUSLS) (without plication), since both procedures are accessible to gynecological surgeons without urologic background. Hence, this study was carried out. Aim To compare both anatomic and functional outcomes of patients undergoing vaginal HUSLS or McCall's culdoplasty at the time of vaginal hysterectomy. Materials and methods This hospital-based prospective comparative study was carried out at a tertiary care hospital from January 1, 2013 to December 31, 2015 over a period of 3 years after obtaining Ethical Committee approval. All women attending gynecological outpatient department having symptom of mass coming out of vagina were subjected to detailed history, examination, and later underwent either HUSLS (43) or McCall's culdoplasty (42), for vault suspension with concomitant hysterectomy. The effectiveness of both the procedures was assessed by preoperative and postoperative pelvic organ prolapse quantification (POP-Q) and both were compared. Observations There was statistically significant improvement in all the sites of POP-Q points by HUSLS and McCall's culdoplasty as a method of vault suspension except in total vaginal length (TVL). Vault suspension by HUSLS is better than McCall's culdoplasty. All the points of POP-Q showed better results but the point C was significantly placed at a higher level by HUSLS (p = 0.000) as compared with McCall's culdoplasty. The time required for HUSLS was statistically more as compared with repair by McCall's culdoplasty (81.55/74.53 minutes, T: 1.981, p: 0.05). Complications, such as hemorrhage and ureteric injuries were more in HUSLS (2/43, 4.8%) as compared with McCall's culdoplasty (0/42); this is statistically significant. Conclusion High uterosacral ligament suspension provides excellent suspensory support to vaginal vault. Vagina is suspended over the levator ani with normal axis toward sacrum. By doing HUSLS, the vagina is symmetrically supported directed toward the hollow of sacrum. High uterosacral ligament suspension is highly recommended for young women with POP as vaginal length is not altered at all and so is the quality of life. How to cite this article Bhalerao AV, Bhalerao K, Garg R. To Compare the Effectiveness of Vaginal High Uterosacral Ligament Suspension and McCall's Culdoplasty during Vaginal Hysterectomy for Pelvic Organ Prolapse. J South Asian Feder Menopause Soc 2017;5(2):81-86.

Aims To investigate the role of pancreastatin inhibitor (PSTi8) in lipid homeostasis and insulin sensitivity in dexamethasone induced fatty liver disease associated type 2 diabetes. Main methods Glucose releases assay, lipid O staining and ATP/AMP ratio were performed in HepG2 cells. Twenty four mice were randomly divided into 4 groups: Control group (saline), DEX (1 mg/kg, im) for 17 days, DEX+PSTi8 (acute 5 mg/kg and chronic 2 mg/kg, ip) for 10 days. The glucose, insulin and pyruvate tolerance tests (GTT, ITT and PTT), biochemical parameters and Oxymax-CLAMS were performed. Further to elucidate the action mechanisms of PSTi8, we performed genes expression and western blotting of biological samples. Key findings We found that PSTi8 suppresses hepatic glucose release, lipid deposition, oxidative stress induced by DEX, stimulates the cellular energy level in hepatocytes and enhances GRP78 activity. It reduces lipogensis and enhances fatty acid oxidation to improve insulin sensitivity and glucose tolerance in DEX induced diabetic mice. The above cellular effects are the result of activated AMPK signalling pathway in liver, which increases Srebp1c and ACC phosphorylation. The increased ACC phosphorylation suppresses protein kinase C activity and enhances insulin sensitivity. The increased expression of UCP3 in liver elicits fatty acid oxidation and energy expenditure, which suppress oxidative stress. Significance Thus the activation of AMPK signalling through GRP78, improves lipid homeostasis, enhances insulin sensitivity via inhibition of PKC activity. PSTi8 suppresses inflammation associated with incomplete fatty acid oxidation. Hence, PSTi8 may be a potential therapeutic agent to treat glucocorticoid-induced fatty liver associated type 2 diabetes.

Bacillus anthracis is the causative agent of anthrax in humans, bovine, and other animals. B. anthracis pathogenesis requires differentiation of dormant spores into vegetative cells. The spores inherit cellular components as phenotypic memory from the parent cell, and this memory plays a critical role in facilitating the spores' revival. Because metabolism initiates at the beginning of spore germination, here we metabolically reprogrammed B. anthracis cells to understand the role of glycolytic enzymes in this process. We show that increased expression of enolase (Eno) in the sporulating mother cell decreases germination efficiency. Eno is phosphorylated by the conserved Ser/Thr protein kinase PrkC which decreases the catalytic activity of Eno. We found that phosphorylation also regulates Eno expression and localization, thereby controlling the overall spore germination process. Using MS analysis, we identified the sites of phosphorylation in Eno, and substitution(s) of selected phosphorylation sites helped establish the functional correlation between phosphorylation and Eno activity. We propose that PrkC-mediated regulation of Eno may help sporulating B. anthracis cells in adapting to nutrient deprivation. In summary, to the best of our knowledge, our study provides the first evidence that in sporulating B. anthracis, PrkC imprints phenotypic memory that facilitates the germination process.

Correction for ‘Simultaneous quantification of five biomarkers in ethanolic extract of Cassia occidentalis Linn. stem using liquid chromatography tandem mass spectrometry: application to its pharmacokinetic studies’ by Mohammed Riyazuddin et al., RSC Adv., 2020, 10, 4579–4588. DOI: 10.1039/C9RA07482A