Development and validation of stability indicating RP-HPLC method for simultaneous estimation of silodosin and mirabegron in synthetic mixture.

The study focuses to validate and develop a precise, simple and accurate stability indicating RP-HPLC method for estimation simultaneously of and silodosin and mirabegron in synthetic mixture. The chromatographic separation was achieved by using Shimpack Solar C18 column (250×4.5mm, 5µm) with acetonitrile: 5mM ammonium acetate in ratio of 90:10% v/v as a mobile phase at a constant flow rate of about 1.2mL/min. The development and validation were carried out at detection wavelength of 229nm. We developed a robust RP-HPLC method, validated for linearity, precision, accuracy, specificity, and system suitability. The method demonstrated excellent linearity with correlation coefficient value r2 was nearly 0.998 with linearity range 8-18µg/mL for Silodosin and 24-54µg/mL for mirabegron. LOD and LOQ were found to be lower; hence, the method is sensitive. Percentage recovery was obtained 99.97% and 99.99% for silodosin and mirabegron, respectively. In case of precision, robustness and repeatability, RSD was found to be less than 2. The validated and developed RP-HPLC method offers an efficient and practical approach for the simultaneous quantification of silodosin and mirabegron in pharmaceutical formulations, making it a valuable tool for quality control and pharmaceutical research.

Rapid and Gentle Immunopurification of Brain Synaptic Vesicles.

Current methods to isolate synaptic vesicles (SVs), the organellar quanta of synaptic transmission, require highly specialized materials and up to 24 h. These technical obstacles have thus far limited the study of SVs in models of synaptic function and pathophysiology. Here, we describe techniques for the rapid isolation of SVs by immunoprecipitation with widely available antibodies conjugated to magnetic beads. We report that the inexpensive rho1D4 monoclonal antibody binds SVs and show that elution with the 1D4 peptide yields native vesicles that are ≥ 10-fold purer than those obtained with classical techniques. These methods substantially widen the accessibility of SVs, enabling their purification in 60-90 min for downstream analyses including mass spectrometry and cryo-electron microscopy. Immunopurified SV preparations from mouse brain contained apolipoprotein E, the LDL receptor Lrp1, and enzymes involved in lipid metabolism, suggesting that SVs may play direct roles in lipid homeostasis and lipoprotein trafficking at the nerve terminal.SIGNIFICANCE STATEMENT SVs are small organelles that form and recycle at nerve terminals to enable synaptic transmission. Much remains unknown about the processes that enable the formation and function of SVs. Moreover, nerve terminals appear to be particularly vulnerable to pathophysiologic processes underlying neurodegenerative diseases and schizophrenia. Although techniques to purify synaptic vesicles thus have the potential to yield significant insights into physiology and pathophysiology of nerve terminals, current methods rely on either esoteric materials or expression of transgenes. This article addresses these problems by establishing robust, efficient methods for SV purification using widely available materials, and it highlights several promising areas of future study arising from proteomic analyses of immunopurified SVs.

Bioisosteric Replacement of Amide Group with 1,2,3-Triazoles in Acetaminophen Addresses Reactive Oxygen Species-Mediated Hepatotoxic Insult in Wistar Albino Rats.

Acetaminophen (AP) is a popularly recommended over-the-counter analgesic-antipyretic in clinical use. However, the drug is handicapped by the occurrence of hepatotoxic insult following acute ingestion. Consequently, AP-induced hepatotoxicity is often implicated in accidental or suicidal overdose. In the current study, we investigated the potential of bioisosteric replacement of amide in AP with 1,2,3-triazoles in curbing AP-induced hepatotoxicity. The therapeutic utility of synthesized bioisosteres was established by careful tailoring and optimization of the synthetic methodology along with detailed toxicological testing of pharmacologically potent acetaminophen-triazole derivatives (APTDs). Along the same lines, we herein report a series of 17 novel APTDs synthesized via aromatic substitution using sodium azide, l-proline, and copper iodide followed by click reaction with substituted alkynes using copper sulfate and sodium ascorbate. Pharmacological evaluation of synthesized APTDs revealed that, out of the series of 17 compounds, 5a and 5e were found to be most efficacious in exerting anti-inflammatory, analgesic, and antipyretic activity in an animal model. Further toxicity studies documented that, in both acute and sub-acute toxicology, AP administration caused significant hepatotoxicity, which was found to be a consequence of ROS-mediated oxidative stress. Potent APTDs (5a and 5e), on the other hand, revealed no adverse event in both acute and sub-toxicological analyses. Median lethal dose (LD50) and no observed adverse effect level (NOAEL) values for 5a and 5e were found to be >1000 mg/kg and 2000 mg/kg, respectively. The human equivalent dose, defining the maximum safe concentration of a compound in a human's physiology, was found to be 27.68 mg/kg for the most potent APTDs (5a and 5e). Thus, it can be concluded that triazole incorporation into AP nucleus produced conjugates devoid of hepatotoxic manifestations, having the added advantage of anti-inflammatory efficacy along with analgesic and antipyretic potency.

Synthesis of Gold(I) Complexes Containing Cinnamide: In Vitro Evaluation of Anticancer Activity in 2D and 3D Spheroidal Models of Melanoma and In Vivo Angiogenesis.

A series of alkynylgold(I) phosphine complexes containing methoxy-substituted cinnamide moieties (3a-3c and 4a-4c) have been synthesized and characterized. All of the synthesized complexes were evaluated for their cytotoxicity against three human cancer cell lines A549 (lung), D24 (melanoma), and HT1080 (fibrosarcoma) and the human embryonic kidney 293 cell line (Hek293T) as a proxy model for noncancer cells. Most of the synthesized compounds showed antiproliferative activity against cancer cell lines at low micromolar concentrations. Among these, complex 3c showed a broad spectrum of anticancer activity with IC50 values in the range of 1.53-6.05 µM against all tested cancer lines. Complex 3c possessed 20 times higher cytotoxicity than the reference drug cisplatin against D24 melanoma cells and showed significant anticancer activity in 3D spheroidal models of melanoma cells. Mechanistic investigations of 3c activity indicate thioredoxin reductase inhibition through steric and hydrogen-bonding interactions, followed by the induction of oxidative stress and a mitochondrial pathway of cell death. Compound 3c also showed significant antiangiogenic properties in a transgenic zebrafish Tg(fli1a:EGFP) in vivo model.

Occurrence of co-existing bla VIM-2 and bla NDM-1 in clinical isolates of Pseudomonas aeruginosa from India.

BACKGROUND: bla VIM-2 harboring Pseudomonas aeruginosa has been reported worldwide and considered as the most prevalent metallo-ß-lactamase after NDM which are found horizontally transferable and mostly associated with integron gene cassettes. The present study investigates the genetic background, transmission dynamics as well as stability of bla VIM-2 in clinical isolates of P. aeruginosa harbor bla NDM-1 as well which were collected from October 2012 to September 2013. METHODS: Two P. aeruginosa strains harboring bla VIM-2 along with bla NDM-1 were isolated from Silchar Medical College and Hospital, India. Genetic environment of these resistance determinants was determined and transferability was checked by transformation and conjugation assay which was further confirmed by Southern hybridization. Replicon typing was performed to determine the incompatibility group of the resistant plasmid and their stability was checked by serial passage method. Antimicrobial susceptibility pattern of the isolates was determined and their clonal relatedness was checked by pulsed field gel electrophoresis. RESULTS: bla VIM-2 was found to be horizontally transferable through an Inc F type plasmid of approximately 30 kb in size. bla VIM-2 was found to be associated with integron gene cassette and was flanked by two different types of cassette arrays. Both the isolates were co-harboring bla NDM-1 which was carried within Inc N type of plasmid with an approximate 24 kb in size and associated with ISAba125 in their upstream region. Reduced susceptibility rate as well as high MIC range was observed in case of wild strains and transformants carrying bla VIM-2 and bla NDM-1. CONCLUSIONS: The detection of this co-existence of multiple carbapenem resistance genes in this part of world is worrisome and further investigation is required in order to trace the source and to initiate proper treatment option.

Long-term outbreak of Klebsiella pneumoniae& third generation cephalosporin use in a neonatal intensive care unit in north India.

BACKGROUND & OBJECTIVES: The indiscriminate use of third generation cephalosporin has contributed to the emergence and widespread dissemination of extended spectrum ß lactamases (ESBL) genes in Klebsiella pneumoniae. This study was undertaken to elaborate the genetic behaviour of ESBL - producing K. pneumoniae isolates in the neonatal intensive care unit (NICU) of a tertiary care hospital in north India causing successive outbreaks in context with empirical third generation cephalosporin use. METHODS: Isolates of K. pneumoniae (43 from blood, 3 from pus and endotracheal tube, 4 from environment) causing successive outbreaks in the NICU of a tertiary care university hospital were studied for two years. Antimicrobial susceptibility testing was done by disc diffusion and minimum inhibitory concentration (MIC) determination by agar dilution methods. ESBL production was determined by phenotypic and genotypic methods. Clonal relatedness among the isolates was studied by enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR). Genetic environment of these isolates was assessed by the presence of integrons and gene cassettes. Transformation experiments were done, and plasmids of these isolates were characterized by stability testing and incompatibility testing. Subsequently, a change in the ongoing antibiotic policy was adopted, and corresponding changes in the behaviour of these isolates studied. RESULTS: During the period from August 2011 to January 2013, 46 isolates of monoclonal ESBL K. pneumoniae were obtained from different neonates and four similar environmental isolates were studied. Multidrug-resistant ESBL isolates harboured both blaCTXM-15 and bla SHV-5. The dfr and aac-6 ' resistant genes were found in gene cassettes. A 50 kb plasmid belonging to IncFIIA group was detected in all the isolates which was transferable and stable. The emergence and regression of the outbreaks coincided with antibiotic usage in the NICU, with widespread empirical use of cefotaxime being responsible for their persistence in the environment. INTERPRETATION & CONCLUSIONS: The study indicates that empirical use of third generation cephalosporins may promote the emergence, persistence, and dissemination of resistant isolates in the hospital environment. Periodic review of antibiotic policy is necessary for rationalized use of antibiotics.

Palliative Surgical Approach in Advanced Nonresponsive Mucinous Ovarian Cancer: A Rare Case Report.

Advanced mucinous ovarian cancer is a separate entity and has different biological behaviour. There is a wide range of therapeutic challenges and dilemmas in the management of these patients. The authors present a case of advanced ovarian mucinous cystadenocarcinoma with pseudomyxoma peritonei who had poor response to standard neoadjuvant chemotherapy. This case is highlighted to emphasize the challenges in the decision making for the management of advanced mucinous ovarian cancer.

Study on individual and interactive effects of supplemental UV-B radiation and heavy metals on Spinacea oleracea.

The effects of supplemental ultraviolet-B (sUV-B) irradiation and heavy metals (Cd and Ni) treatment alone and in combination were evaluated on the growth, biomass and yield of spinach plants. All the stresses caused reduction in biomass yield vis-a-vis alteration in its distribution pattern with more retention in below ground parts leading to higher root shoot ratio. Absolute growth rate (AGR) decreased in all treated plants due to reduction in their height at successive growth stages. Decrease in leaf area and number of leaves due to various stresses was responsible for decline in net assimilation rate (NAR), an index of photosynthetic assimilatory capacity of the plant. Supplemental UV-B increased the bioaccumulation of Cd and Ni in the root and shoot of exposed plants as compared to the control ones. The present study suggested that soil contaminated with Cd or Ni had a more negative impact on yield with higher retention of heavy metals in spinach growing under natural field conditions and exposed with elevated UV-B.

New Excipient For Oral Drug Delivery: CNC Derived From Sugarcane Bagasse-Derived Microcrystalline Cellulose.

Nanocrystalline cellulose (CNC) has emerged as a subject of researcher's interest because of its diverse attributes encompassing biocompatibility, sustainability, a high aspect ratio, and an abundance of -OH groups suitable for modifications. Sugarcane bagasse microcrystalline cellulose (SCBMCC) was used as the raw material for the preparation of CNC due to its pure cellulose content, which is mildly compromised by the pectin, hemicellulose, lignin, and other lignocellulosic components. In the present work, CNC was extracted from SCBMCC and used as a disintegrant. The classic hydrolysis technique was used for the preparation of CNC. Hydrolytic conditions were optimized using the response surface methodology (RSM). The optimized batch of CNC was characterized using techniques such as field-emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. Notably, CNC prepared under a hydrolysis time of 90 min exhibited the highest crystallinity of 69.9%. The average particle size and zeta potential were found to be 145 nm and -34.4 mV, respectively. Thermal analysis suggested that an intermediate hydrolysis time resulted in CNC with enhanced thermal stability, showcasing its potential for pharmaceutical applications. Diclofenac potassium was used as the model drug to evaluate the disintegrant properties of CNC as an excipient. Tablets were prepared using the direct compression method. SCBMCC and CNC were used as disintegrants and were compared with the commercial product. The disintegration times (DTs) attained for the tablets prepared using CNC and SCBMCC are 219 and 339.83 s, respectively. The dissolution study of CNC showed a dissolution efficacy (DE%) of 66 and a mean dissolution time (MDT) of 12. The research findings showed that tablets prepared using CNC as disintegrants exhibited the fastest disintegration compared to other formulations.

Efficacy of the QuitSure App for Smoking Cessation in Adult Smokers: Cross-Sectional Web Survey.

BACKGROUND: Cigarette smoking remains one of the leading causes of preventable death worldwide. A worldwide study by the World Health Organization concluded that more than 8 million people die every year from smoking, tobacco consumption, and secondhand smoke. The most effective tobacco cessation programs require personalized human intervention combined with costly pharmaceutical supplementation, making them unaffordable or inaccessible to most tobacco users. Thus, digital interventions offer a promising alternative to these traditional methods. However, the leading smartphone apps available in the market today have either not been studied in a clinical setting or are unable to match the smoking cessation success rates of their expensive offline counterparts. We would like to understand whether QuitSure, a novel smoking cessation app built by Rapidkart Online Private Limited, is able to bridge this efficacy gap and deliver affordable and effective smoking cessation at scale. OBJECTIVE: Our objective was to do an initial exploration into the engagement, efficacy, and safety of QuitSure based on the self-reported experiences of its users. Outcomes measured were program completion, the effect of program completion on smoking behavior, including self-reported cessation outcomes, and negative health events from using the app. METHODS: All QuitSure registered users who created their accounts on the QuitSure app between April 1, 2021, and February 28, 2022, were sent an anonymized web-based survey. The survey results were added to their engagement data on the app to evaluate the feasibility and efficacy of the app as a smoking cessation intervention. The data were analyzed using descriptive statistics (frequencies and percentages) and the χ2 test of independence. RESULTS: In total, 1299 users who had completed the QuitSure program submitted the survey and satisfied the inclusion criteria of the study. Of these, 1286 participants had completed the program more than 30 days before filling out the survey, and 1040 (80.1%, 95% CI 79.1%-82.6%) of them had maintained prolonged abstinence for at least 30 days after program completion. A majority of participants (770/891, 86.4%) who were still maintaining abstinence at the time of submitting the survey did not experience any severe nicotine withdrawal symptoms, while 41.9% (373/891) experienced no mild withdrawal symptoms either. Smoking quantity prior to completing the program significantly affected quit rates (P<.001), with heavy smokers (>20 cigarettes per day) having a lower 30-day prolonged abstinence rate (relative risk=0.91; 95% CI 90.0%-96.2%) compared to lighter smokers. No additional adverse events outside of known nicotine withdrawal symptoms were reported. CONCLUSIONS: The nature of web-based surveys and cohort selection allows for extensive unknown biases. However, the efficacy rates of survey respondents who completed the program were high and provide a case for further investigation in the form of randomized controlled trials on the QuitSure tobacco cessation program.

Comparing Radiation Doses in CBCT and Medical CT Imaging for Dental Applications.

Background: Dental imaging plays a crucial role in diagnosis and treatment planning, with cone-beam computed tomography (CBCT) and medical computed tomography (CT) being two common modalities. This study aims to compare the radiation doses associated with CBCT and medical CT imaging in dental applications to assess their relative safety and efficacy. Materials and Methods: We conducted a retrospective study using data from 100 patients who underwent both CBCT and medical CT scans for dental purposes. The radiation doses were measured in terms of dose-length product (DLP) for medical CT and dose-area product (DAP) for CBCT. The effective dose (ED) was calculated using appropriate conversion factors. Patient demographics, scan parameters, and radiation doses were recorded and analyzed. Results: The results indicated that the mean DLP for medical CT scans was 220 mGycm, whereas the mean DAP for CBCT scans was 150 mGycm². The corresponding mean effective doses for medical CT and CBCT were 2.5 mSv and 1.8 mSv, respectively. The radiation dose from CBCT was found to be approximately 28% lower than that from medical CT. Conclusion: This study demonstrates that CBCT imaging for dental applications results in significantly lower radiation doses compared to medical CT. While both modalities provide valuable diagnostic information, the choice of imaging technique should consider the balance between diagnostic quality and radiation exposure, especially for pediatric and high-risk patients. Dental practitioners should be aware of the potential dose reduction benefits associated with CBCT when appropriate for the clinical scenario.

Therapeutic potential of vasopressin in the treatment of neurological disorders.

Vasopressin (VP) is a nonapeptide made of nine amino acids synthesized by the hypothalamus and released by the pituitary gland. VP acts as a neurohormone, neuropeptide and neuromodulator and plays an important role in the regulation of water balance, osmolarity, blood pressure, body temperature, stress response, emotional challenges, etc. Traditionally VP is known to regulate the osmolarity and tonicity. VP and its receptors are widely expressed in the various region of the brain including cortex, hippocampus, basal forebrain, amygdala, etc. VP has been shown to modulate the behavior, stress response, circadian rhythm, cerebral blood flow, learning and memory, etc. The potential role of VP in the regulation of these neurological functions have suggested the therapeutic importance of VP and its analogues in the management of neurological disorders. Further, different VP analogues have been developed across the world with different pharmacotherapeutic potential. In the present work authors highlighted the therapeutic potential of VP and its analogues in the treatment and management of various neurological disorders.

Potential role of oxytocin in the regulation of memories and treatment of memory disorders.

Oxytocin (OXT) is an "affiliative" hormone or neurohormone or neuropeptide consists of nine amino acids, synthesized in magnocellular neurons of paraventricular (PVN) and supraoptic nuclei (SON) of hypothalamus. OXT receptors are widely distributed in various region of brain and OXT has been shown to regulate various social and nonsocial behavior. Hippocampus is the main region which regulates the learning and memory. Hippocampus particularly regulates the acquisition of new memories and retention of acquired memories. OXT has been shown to regulate the synaptic plasticity, neurogenesis, and consolidation of memories. Further, findings from both preclinical and clinical studies have suggested that the OXT treatment improves performance in memory related task. Various trials have suggested the positive impact of intranasal OXT in the dementia patients. However, these studies are limited in number. In the present study authors have highlighted the role of OXT in the formation and retrieval of memories. Further, the study demonstrated the outcome of OXT treatment in various memory and related disorders.

Ferric carboxymaltose: A game changer in the management of iron deficiency anaemia in pregnancy.

Anaemia is a well-known global health concern in the South Asian countries, and it is estimated that India has the utmost prevalence of anaemia and maternal deaths due to iron deficiency anaemia. This study aims to assess the efficacy and safety of intravenous ferric carboxymaltose (FCM) in antenatal women with anaemia in the second and third trimesters of pregnancy. Methods: A single-arm prospective cohort (before-after) study among 60 antenatal women with moderate to severe anaemia in the second and third trimesters was conducted from December 2020 to December 2022, and the eligible women were given 1000 mg of intravenous FCM injection. Efficacy was assessed by rate of improvement in haemoglobin and ferritin at 2 weeks post infusion. Safety analysis was done by assessing adverse drug reactions and foetal heart monitoring during the infusion. Results: A total 60 antenatal women with a median gestational age of 32.5 weeks at presentation received 1000 mg of intravenous FCM. There was a rise in mean haemoglobin from 8.05 gm% pre-infusion to 10.93 gm% 2 weeks post infusion, showing a mean rise of 2.88 gm%. Similar improvement was noted in mean serum ferritin levels from 25.92 pre-infusion to 253.96 post FCM infusion. There were no reports of drug-related major adverse effects in the mother or the foetus. Conclusions: FCM is found to be safe and effective treatment with rapid replenishment of haemoglobin and ferritin levels in a single dose, which makes it suitable and compels consideration as the first choice for treatment of iron-deficiency anaemia.

Impact of fibromyalgia severity on patients mood, sleep quality, and quality of life.

Objectives: Fibromyalgia syndrome (FMS) is characterized by persistent widespread pain which greatly impacts the quality of life (QOL). Pain not only limits patients' daily activities but also restricts their social activities further leading to depression, anxiety, and stress. The present cross-sectional study elucidated the association of sleep quality and mood with increasing symptom severity of fibromyalgia and its impact on the QOL of fibromyalgia patients. Materials and Methods: Hundred adult fibromyalgia patients diagnosed by the American College of Rheumatology 2010 criteria were evaluated for: sleep - using the Pittsburgh sleep quality index, QOL by SF-36, pain-visual analog scales (VASs) and global pain scale (GPS), mood-depression, anxiety, stress scale-21, somatic symptoms, anxiety and depression - by patients health questionnaire somatic, anxiety, and depressive symptom scales (PHQ-SADS), and FMS severity was evaluated using fibromyalgia impact questionnaire (FIQR). Results: The mean pain score was 6.80 ± 1.58 on VAS and 54.10 ± 14.33 on GPS. FIQR score was 50.62 ± 13.68, mean sleep quality was poor (9.30 ± 3.88), and depression, anxiety, and stress scores were increased (10.04 ± 4.59, 8.33 ± 4.48, and 10.75 ± 4.66). An increasing trend of depression, anxiety, stress, and somatoform symptoms was observed with an increase in the severity of FMS when patients were compared according to FMS severity scores. Sleep also deteriorated with increasing severity of FMS from 5.66 ± 1.92 in mild FMS to 12.0 ± 3.41 in highly severe FMS patients. The QOL too deteriorated in all the domains with increasing severity. Conclusion: With the increasing severity of fibromyalgia, not only does the pain increase but mood and sleep quality also deteriorate, which further impacts the QOL of FMS patients. Thus, comorbid mood derangements must also be screened and addressed for maximum benefit of the patients.

Genomics and Drug Discovery Strategies: The Role of Natural Compounds and Its Receptor in Alzheimer's Disease.

Alzheimer's Disease (AD) is a special class of neurodegenerative diseases demarcated as a progressive disorder affecting especially older adults globally. The AD-infected brain shows declination in cognitive functions, memory loss, and other exhausting symptoms. In this study, we focused on using advanced bioinformatics and next-generation sequencing to explore essential clusters of genes from various diversified Alzheimer's, Parkinson and Frontotemporal Dementia diseased cases. The significant differential expression analysis of genes (p-value ≤ 0.05, log fold change ≤ 0.05) was carried out, followed by meta-analysis, which resulted in the identification of 20 conserved genes across variable case studies. Out of 20 conserved genes, CASP8 and PTPN11 were observed to show essential regulatory mechanisms in AD metabolic pathways and proceeded further for docking analysis. Moreover, the natural compounds were screened for ligand library preparation based on extensive scientific literature and (ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity)) property check. Molecular docking was carried out with screened ligands and target receptors, resulting in the identification of Rosmarinic acid (RA) with CASP8 having docked score (∆G = -8.0 kcal/mol); Donepezil (FDA drug) dock score (∆G = -7.3 kcal/mol) (control). PTPN11 receptor with Carnosol ligand resulted in docking score (∆G = -9.1 kcal/mol) w.r.t Tacrine (FDA drug) docked score (∆G = -8.0 kcal/mol) followed by MD simulation. This research will aid in the identification of potential natural compounds that future researchers can use for further validation as a potential candidate drug in combating various neurodegenerative diseases highlighting AD.

Time Trend and Prevalence Analysis of Transfusion Transmitted Infections among Blood Donors: A Retrospective Study from 2001 to 2016.

Context: Transfusion-transmitted infections (TTIs) remain a major threat to the patients receiving blood. The incidence of the transmission of various infectious agents has reduced ever since the introduction of various molecular techniques for detection. Aims: The study tried to figure out accurate estimates of risk and trend of TTI over a period of sixteen years, essential for monitoring the safety of blood supply and evaluating the efficacy of the currently employed screening procedures. Methods and Material: A total of 57942 blood donors' records were analyzed for the period from January 2001 to December 2016. Chi-square test (χ2) was used to evaluate the relationship between serological positivity and particular donor characteristics. A P value of less than 0.05 was considered statistically significant. Results: Of the 57942 donations, overall prevalence of TTI was 2.7%. Of these, the reactivity rate of hepatitis B (HBV), hepatitis C, HIV, syphilis, and malaria was 1.8%, 0.42%, 0.2%, 0.31%, and 0.017%, respectively with significant P value (P < 0.05, CI: 95%). Overall prevalence was higher in replacement donors as compared to voluntary blood donors. Trend of TTI prevalence decreased from 2001 to 2016. Conclusions: This epidemiological research on TTI is important for the region, as estimated disease burden based on comprehensive epidemiological research provides the foundation for public policy to ensure an easily accessible and adequate supply of safe and quality blood and blood components to the needy patients.

A Comparative Study of Sublingual Misoprostol Versus Intramuscular Oxytocin in the Active Management of Third Stage of Labor.

Objective Misoprostol has attracted low-income low-resource countries for the active management of the third stage of labor. The objective of this study was to compare the efficacy of sublingual misoprostol and intramuscular oxytocin in the active management of the third stage of labor. Study design This was a prospective randomized controlled trial in which a total of 407 healthy pregnant women having singleton pregnancy, cephalic presentation, and normal vaginal delivery were divided into two groups. In the first group (n=203), women received 600 µg misoprostol tablet sublingually, and in the second group (n=204), women received 10 IU of intramuscular oxytocin, within 1 minute of the delivery of the baby during the third stage of labor. Three patients from the first group and four patients from the second group were excluded from the analysis due to traumatic postpartum hemorrhage (PPH). The primary outcome was an incidence of PPH. Secondary outcomes were the duration of the third stage of labor, amount of blood loss, fall in hemoglobin concentration after 48 hours of delivery, need for additional uterotonics, and side effects of the drugs. Data were compared using the chi-square and independent samples t-test. Results The incidence of PPH was 6.5% in the misoprostol group as compared to 2% in the oxytocin group (p=0.026). The misoprostol group also had significantly higher blood loss (293.75±125.8 mL) and a greater fall in hemoglobin level (0.58±0.25 g/dL) as compared to that in the oxytocin group (226.13±98.44 mL and 0.45±0.20 g/dL) (p<0.001). The mean duration of the third stage of labor was significantly higher in the misoprostol group (5.31±2.1 min) as compared to that in the oxytocin group (3.65±1.75 min) (p<0.001). The additional need for uterotonics was recorded in 15% of the study participants in the misoprostol group as compared to 8% in the oxytocin group (p=0.028). The incidence of side effects such as shivering and fever was significantly higher in the misoprostol group as compared to the oxytocin group. No significant difference between the two groups was observed concerning the incidence of nausea, vomiting, diarrhea, and headache. Conclusion Intramuscular oxytocin is a safe and useful alternative to sublingual misoprostol in facilitating the third stage of labor with minimal blood loss, fewer incidences of hemorrhage, and fewer adverse effects.

Effectiveness of the QuitSure Smartphone App for Smoking Cessation: Findings of a Prospective Single Arm Trial.

BACKGROUND: Digital therapies, especially smartphone apps for active and continuous smoking cessation support, are strongly emerging as an alternative smoking cessation therapy. In the Indian context, there is a growing interest in the use of app-based smoking cessation programs; however, there is limited evidence regarding their effectiveness in achieving long-term continuous abstinence. OBJECTIVE: This study aimed to evaluate the long-term abstinence effect (up to 30-d abstinence postprogram completion) of a smartphone app, QuitSure, for smoking cessation in active smokers from India. METHODS: In this prospective single-arm study, participants who signed up for the QuitSure app were enrolled in this study. The primary end point was the prolonged abstinence (PA) rate from weeks 1 to 4 (day 7 to day 30). Furthermore, data for withdrawal symptoms, relapse reasons, and reasons for not continuing the program were also assessed. RESULTS: The quit rate was calculated considering only the participants who followed up and completed the survey sent to them (per protocol) at day 7 and at day 30, respectively. The PA rate at day 7 was found to be 64.5% (111/172; 95% CI 56% to 72%), and the PA rate at day 30 was found to be 55.8% (72/129; 95% CI 45% to 65%). Within the 7-day abstinence period, 60.4% (67/111) of the participants did not have any withdrawal symptoms. The most common mild withdrawal symptoms were mild sleep disturbance (21/111, 18.9%), mild digestive changes (19/111, 17.1%), and coughing (17/111, 15.3%). Severe withdrawal symptoms were rare, with only 5.4% (6/111) experiencing them. For those achieving 30-day postprogram abstinence, 85% (61/72) had no mild withdrawal symptoms, and 99% (71/72) had no severe withdrawal symptoms. Among successful quitters at day 7, a total of 72.1% (80/111) reported minimal to no cravings, which increased to 88% (63/72) at day 30. Furthermore, 78% (56/72) of those with PA at day 30 reported no change in weight or reduced weight. Among participants experiencing relapse, 48% (28/58) cited intense cravings, 28% (16/58) mentioned facing a tragedy, and 26% (15/58) reported relapsing due to alcohol consumption. The PA rates as a result of the QuitSure program were found to be better than those reported in the results of other smoking-cessation app programs' studies. CONCLUSIONS: The QuitSure app yields high PA rates and ameliorates symptoms associated with smoking cessation. In order to obtain conclusive evidence regarding the effectiveness and efficacy of the QuitSure program, future research should include appropriate control measures. Nevertheless, the QuitSure program can serve as a valuable adjunct to a conventional smoking cessation treatment program to aid sustained abstinence.

Recent Development in the Search for Epidermal Growth Factor Receptor (EGFR) Inhibitors based on the Indole Pharmacophore.

The signal transduction and cell proliferation are regulated by the epidermal growth factor receptor. The proliferation of tumor cells, apoptosis, invasion, and angiogenesis is inhibited by the epidermal growth factor receptor. Thus, breast cancer, non-small cell lung cancer, cervical cancer, glioma, and bladder cancer can be treated by targeting the epidermal growth factor receptor. Although third-generation epidermal growth factor receptor inhibitors are potent drugs, patients exhibit drug resistance after treatment. Thus, the search for new drugs is being continued. Among the different potent epidermal growth factor receptor inhibitors, we have reviewed the indole-based inhibitors. We have discussed the structure-activity relationship of the compounds with the active sites of the epidermal growth factor receptor receptors, their synthesis, and molecular docking studies.