Expert Consensus on Dipeptidyl Peptidase-4 Inhibitor-Based Therapies in the Modern Era of Type 2 Diabetes Mellitus Management in India.

India has a high prevalence of type 2 diabetes mellitus (T2DM) with unique clinical characteristics compared to other populations. Despite advancements in diabetes therapy, a significant number of patients in India still experience poor glycemic control and complications. Dipeptidyl peptidase-4 (DPP-4) inhibitors continue to be an important component of T2DM treatment due to their favorable efficacy and tolerability profile. Given the current scenario, there is a need to revisit the role of DPP-4 inhibitors in T2DM management in Indian patients. This consensus paper aims to provide guidance on the utilization of DPP-4 inhibitors in T2DM management from an Indian perspective. A consensus group of 100 experts developed recommendations based on an extensive literature review and discussions. The expert group emphasized the importance of timely glycemic control, combination therapy, and targeting the underlying pathophysiology of T2DM. The combinations of DPP-4 inhibitors with metformin and/or sodium-glucose transport protein-2 inhibitors are rationalized in this paper, considering their complementary mechanisms of action. This paper provides valuable insights for clinicians in optimizing the management of T2DM in the Indian population with the use of DPP-4 inhibitors and proposes an algorithm for selecting DPP-4 inhibitor-based therapies.

Diagnosis and management of common sleep disorders during the perinatal period.

The perinatal period is a critical phase in a woman's life characterized by significant physical, emotional, and societal changes. Sleep disorders such as insomnia, restless legs syndrome, obstructive sleep apnea, and poor sleep quality have been observed to increase in prevalence during the perinatal period. Given the harmful impact of sleep disturbances on the health of both mother and newborn, it is crucial to diagnose and treat them promptly. There is a paucity of literature on sleep problems during the perinatal period. This narrative review aimed to summarize the existing evidence and provide suggestions for promptly identifying and managing these disorders.

Targeting Adipokines: A Promising Therapeutic Strategy for Epilepsy.

Epilepsy affects 65 million people globally and causes neurobehavioral, cognitive, and psychological defects. Although research on the disease is progressing and a wide range of treatments are available, approximately 30% of people have refractory epilepsy that cannot be managed with conventional medications. This underlines the importance of further understanding the condition and exploring cutting-edge targets for treatment. Adipokines are peptides secreted by adipocyte's white adipose tissue, involved in controlling food intake and metabolism. Their regulatory functions in the central nervous system (CNS) are multifaceted and identified in several physiology and pathologies. Adipokines play a role in oxidative stress and neuroinflammation which are associated with brain degeneration and connected neurological diseases. This review aims to highlight the potential impacts of leptin, adiponectin, apelin, vaspin, visfatin, and chimerin in the pathogenesis of epilepsy.

Confronting multidrug-resistant Klebsiella meningitis after mid-clival Cerebrospinal Fluid leak repair: a therapeutic odyssey.

A man in his 40s with type 2 diabetes mellitus had persistent right-sided watery nasal discharge for 6 months following cerebrospinal fluid (CSF) leak repair at another hospital, prompting his visit to us due to recurring symptoms. Imaging revealed a CSF leak from the mid-clivus for which revision endoscopic CSF leak repair was done. Regrettably, he developed postoperative meningitis caused by multidrug-resistant (MDR) Klebsiella pneumoniaeManaging this complex case was a challenging task due to the pathogen's resistance to conventional drugs and the scarcity of scientific evidence. We initiated a culture-guided combination regimen with ceftazidime, avibactam, aztreonam and tigecycline. This decision stemmed from meticulous literature review and observed antibiotic synergy while testing for this organism.After 4 weeks of vigilant treatment, the patient's symptoms improved significantly, and CSF cultures were sterile. We present our approach to effectively confront and manage a challenging instance of postoperative MDR bacterial meningitis.

Lacrimal sac Aspergillosis Masquerading as Malignancy: A Rare Case Report.

Invasive fungal infections are uncommon in an immunocompetent host and pose a real diagnostic dilemma. As they have a propensity for locoregional destruction, clinic-radiological findings can mislead to a faulty diagnosis of a malignancy. Here we present a case of Primary Aspergillus dacryocystitis in an immunocompetent individual initially thought to be an orbital malignancy until the histopathological examination.

Correlation of anthropometric measurements with body mass index and estimation of the proportion of metabolic syndrome among overweight and obese children: a hospital-based cross-sectional study.

BACKGROUND: Early identification of overweight and obesity with the help of simple anthropometric tests can prevent from development of metabolic complications in these children. Body mass index (BMI) is the most commonly used parameter but, measurements such as waist circumference (WC), waist-to-height ratio (WHtR) and wrist circumference (WrC) have also been studied and found to have a better correlation with visceral fat. OBJECTIVE: To correlate WC, WHtR and WrC with BMI among overweight and obese children. The secondary objective was to estimate the proportion of metabolic syndrome among obese and overweight children. METHODS: A single-centre, cross-sectional study involving 80 overweight and obese children aged 3-15 years. Anthropometric measures such as WC, WHtR and WrC of the study subjects were correlated with BMI and investigated for metabolic syndrome. RESULTS: Statistically significant and moderate positive correlation was found between BMI and WC, r (80)=0.45 and p<0.001 with WC explaining 20% of the variation of BMI. There was a statistically significant, moderate positive correlation between WHtR and BMI r (80)=0.34 and p<0.001 with 11% of the variation in BMI. There was a statistically significant strong positive correlation between WC and WrC (80)=0.61 and p<0.001, and WrC explains 37.2% of the variation in WC. However, there was no statistically significant correlation between BMI and WrC. Metabolic syndrome was found in 13 (16.25%) children. CONCLUSION: Alternative anthropometric measurements such as WC and WHtR have a significant correlation with BMI and may be of help in defining overweight and obesity in children. There was a statistically significant strong positive correlation between WC and WrC among obese children. Metabolic syndrome is common in these children.

In silico studies and development of a protein-based electrochemical sensor for selective and sensitive detection of aflatoxin B1.

Proteins from different species have been docked with aflatoxin B1 (AFB1) and identified 3 proteins (prostaglandin-E(2)9-reductase from Oryctolagus uniculus, proto-oncogene serine/threonine-protein kinase Pim-1 and human immunoglobulin G (hIgG)) as potential candidates to develop an electrochemical sensor. Fluorescence spectroscopy experiments have confirmed the interaction of hIgG with AFB1 with an affinity constant of 4.6 × 105 M-1. As a proof-of-concept, hIgG was immobilized on carbon nanocomposite (carbon nanotube-nanofiber, CNT-F)-coated glassy carbon electrode (GCE). FT-IR spectra, HR-TEM and BCA assay have confirmed successful immobilization of hIgG on the electrode (hIgG@CNT-F/GCE). The preparation of this protein electrochemical sensor requires only 1 h 36 min, which is fast as compared with preparing an electro immunosensor. hIgG@CNT-F/GCE has displayed an excellent AFB1 limit of detection (0.1 ng/mL), commendable selectivity in the presence of two other mycotoxins (ochratoxin A and patulin) and the detection of  AFB1 in spiked peanuts and corn samples.

Optic nerve sheath diameter as a non-invasive tool to detect clinically relevant raised intracranial pressure in children: an observational analytical study.

BACKGROUND: Raised intracranial pressure (ICP) contributes to approximately 20% of the admissions in the paediatric intensive care unit (PICU) in our setting. Timely identification and treatment of raised ICP is important to prevent brain herniation and death in such cases. The objective of this study was to examine the role of optic nerve sheath diameter (ONSD) in detecting clinically relevant raised ICP in children. METHODS: A hospital-based observational analytical study in a PICU of a tertiary care institute in India on children aged 2-14 years. ONSD was measured in all children on three time points that is, day 1, day 2 and between day 4 and 7 of admission. ONSD values were compared between children with and without clinical signs of raised ICP. RESULTS: Out of 137 paediatric patients recruited, 34 had signs of raised ICP. Mean ONSD on day 1 was higher in children with signs of raised ICP (4.99±0.57 vs 4.06±0.40; p<0.01). Mean ONSD on day 2 also was higher in raised ICP patients (4.94±0.55 vs 4.04±0.40; p<0.01). The third reading between days 4 and 7 of admission was less than the first 2 values but still higher in raised ICP patients (4.48±1.26 vs 3.99±0.57; p<0.001). The cut-off ONSD value for detecting raised ICP was 4.46 mm on the ROC curve with an area under curve 0.906 (95% CI 0.844 to 0.968), 85.3% sensitivity and 86.4% specificity. There was no difference in ONSD between the right and the left eyes at any time point irrespective of signs of raised ICP. CONCLUSION: We found that measurement of ONSD by transorbital ultrasound was able to detect clinically relevant raised ICP with an excellent discriminatory performance at the cut-off value of 4.46 mm.

Artesunate attenuates isoprenaline induced cardiac hypertrophy in rats via SIRT1 inhibiting NF-κB activation.

Cardiac Hypertrophy is an adaptive response of the body to physiological and pathological stimuli, which increases cardiomyocyte size, thickening of cardiac muscles and progresses to heart failure. Downregulation of SIRT1 in cardiomyocytes has been linked with the pathogenesis of cardiac hypertrophy. The present study aimed to investigate the effect of Artesunate against isoprenaline induced cardiac hypertrophy in rats via SIRT1 inhibiting NF-κB activation. Experimental cardiac hypertrophy was induced in rats by subcutaneous administration of isoprenaline (5 mg/kg) for 14 days. Artesunate was administered simultaneously for 14 days at a dose of 25 mg/kg and 50 mg/kg. Artesunate administration showed significant dose dependent attenuation in mean arterial pressure, electrocardiogram, hypertrophy index and left ventricular wall thickness compared to the disease control group. It also alleviated cardiac injury biomarkers and oxidative stress. Histological observation showed amelioration of tissue injury in the artesunate treated groups compared to the disease control group. Further, artesunate treatment increased SIRT1 expression and decreased NF-kB expression in the heart. The results of the study show the cardioprotective effect of artesunate via SIRT1 inhibiting NF-κB activation in cardiomyocytes.

PAQR4 oncogene: a novel target for cancer therapy.

Despite decades of basic and clinical research and trials of promising new therapies, cancer remains a major cause of morbidity and mortality due to the emergence of drug resistance to anticancer drugs. These resistance events have a very well-understood underlying mechanism, and their therapeutic relevance has long been recognized. Thus, drug resistance continues to be a major obstacle to providing cancer patients with the intended "cure". PAQR4 (Progestin and AdipoQ Receptor Family Member 4) gene is a recently identified novel protein-coding gene associated with various human cancers and acts through different signaling pathways. PAQR4 has a significant influence on multiple proteins that may regulate various gene expressions and may develop chemoresistance. This review discusses the roles of PAQR4 in tumor immunity, carcinogenesis, and chemoresistance. This paper is the first review, discussing PAQR4 in the pathogenesis of cancer. The review further explores the PAQR4 as a potential target in various malignancies.

An Overview of SARS-CoV-2 Potential Targets, Inhibitors, and Computational Insights to Enrich the Promising Treatment Strategies.

The rapid spread of the SARS-CoV-2 virus has emphasized the urgent need for effective therapies to combat COVID-19. Investigating the potential targets, inhibitors, and in silico approaches pertinent to COVID-19 are of utmost need to develop novel therapeutic agents and reprofiling of existing FDA-approved drugs. This article reviews the viral enzymes and their counter receptors involved in the entry of SARS-CoV-2 into host cells, replication of genomic RNA, and controlling the host cell physiology. In addition, the study provides an overview of the computational techniques such as docking simulations, molecular dynamics, QSAR modeling, and homology modeling that have been used to find the FDA-approved drugs and other inhibitors against SARS-CoV-2. Furthermore, a comprehensive overview of virus-based and host-based druggable targets from a structural point of view, together with the reported therapeutic compounds against SARS-CoV-2 have also been presented. The current study offers future perspectives for research in the field of network pharmacology investigating the large unexplored molecular libraries. Overall, the present in-depth review aims to expedite the process of identifying and repurposing drugs for researchers involved in the field of COVID-19 drug discovery.

Green route to fabrication of Semal-ZnO nanoparticles for efficient solar-driven catalysis of noxious dyes in diverse aquatic environments.

This work successfully demonstrates a sustainable and environmentally friendly approach for synthesizing Semal-ZnO nanoparticles (NPs) using the aqueous leaf extract of Bombax ceiba L. These NPs exhibit an absorption peak at approximately 390 nm in the UV-visible spectrum and an energy gap (Eg) of 3.11 eV. Detailed analyses of the morphology and particle size using various spectroscopic and microscopic techniques, XRD, FE-SEM with EDS, and HR-TEM reveal crystallographic peaks attributable to the hexagonal phase, with an average crystal size of 17 nm. The Semal-ZnO NPs also exhibit a notable photocatalytic efficiency for degrading methylene blue (MB) and methyl orange (MO) under sunlight in different water samples collected from diverse natural sources, indicating that they are promising photocatalysts for environmental remediation. The photocatalytic efficiency of the biofabricated Semal-ZnO NPs is impressive, exhibiting a photodegradation rate of up to 99% for MB and 79% for MO in different water samples under exposure to sunlight. The novel phytofabricated Semal-ZnO NPs are thus a beacon of hope for the environment, with their desirable photocatalytic efficiency, pseudo-first-order kinetics, and ability to break down noxious dye pollutants in various aquatic environments.

Unmasking the Masquerade: Lessons from a Case of Spontaneous Mid-Clival CSF Leak Mimicking an Ethmoidal Leak.

Spontaneous cerebrospinal fluid (CSF) leaks are an uncommon clinical entity, often challenging to diagnose accurately. We present a unique case of a patient with symptoms suggestive of an ethmoidal CSF leak, initially supported by radiological findings, but ultimately revealed to be a mid-clival CSF leak (from the posterior wall of the sphenoid sinus). This case underscores the complexities of diagnosing CSF leaks and highlights the importance of surgical exploration in cases where radiological evidence appears contradictory. The patient's Computed Tomography scan indicated a CSF leak in the cribriform plate, prompting a surgical approach to address this region. However, intraoperative findings surprisingly revealed no evidence of leak in the cribriform plate but instead a posterior wall of the sphenoid defect as the culprit. This report emphasizes the critical role of interdisciplinary collaboration, meticulous preoperative and intraoperative assessment, and adaptability in managing challenging cases of CSF leaks, ultimately leading to successful surgical repair and improved patient outcomes. It serves as a valuable reminder for clinicians to consider the possibility of a masquerading CSF leak when clinical and radiological findings do not align, thereby facilitating more precise diagnosis and targeted treatment.

Malignant Otitis Externa: Unveiling the Hidden Danger of ICA Pseudoaneurysm.

Pseudoaneurysm of the internal carotid artery following otogenic infection is rare but leads to catastrophic outcomes. In our case series, we present two patients with ICA pseudoaneurysm complicated by malignant otitis externa, and we emphasise the importance of timely diagnosis and management to prevent fatal outcomes. A pseudoaneurysm should be ruled out in a patient with malignant otitis externa presenting with recurrent epistaxis or ear bleed.

Prevalence and predictors of restless legs syndrome among patients having stable chronic obstructive pulmonary disease.

BACKGROUND: Patients having COPD share some factors, e.g., chronic hypoxemia, anemia of chronic disease and nicotine use, which are also the risk factors for RLS hence predispose them to experience RLS in higher then general population. There are limited studies with methodological constraints evaluating the prevalence and/or correlates of RLS among patients with COPD. METHODS: Consecutive adult patients of either gender, having stable COPD as per GOLD guidelines 2021, were assessed for RLS using IRLSSG (2014) criteria (excluding RLS mimics) and the severity of RLS was determined in participants having RLS. Phenomenology of RLS, past medical history and laboratory parameters were gathered. Insomnia and depression were assessed using the insomnia severity index and PHQ-9, respectively. RESULTS: Participants' (N = 210) mean age was 63.02 ± 8.19 years, and 83.8% of subjects were men. 12.9% of participants were found to have RLS. Among those having RLS, nearly half (51.9%) had moderate symptoms, and 18.5% experienced severe symptoms. RLS was more prevalent among younger, females, those having severe COPD, participants having exacerbation of COPD in the previous year, lower post-bronchodilator FEV1, higher dyspnea and COPD assessment test score. Multivariate analysis showed that younger age, female gender, lower post-bronchodilator FEV1, lower FEV1/FVC ratio and higher serum creatinine increased the odds of having RLS. Depressive symptoms were more frequent in participants having RLS. CONCLUSIONS: The present study found that the prevalence of RLS among patients with stable COPD was higher than the general population. Female gender, younger age, higher airflow limitation and higher serum creatinine (though in the physiological range) increase the odds of having RLS. Stable patients with COPD having these characteristics must be screened for RLS.

Tumescent solution: a game changer in excising refractory arteriovenous malformation.

Arteriovenous malformations of the head and neck are rare and inborn errors of vascular morphogenesis. They pose therapeutic challenges owing to their bleeding tendency and a high chance of recurrence. Treatment modalities include digital subtraction angiography with embolisation as a primary treatment or can be done preoperatively followed by surgical excision. We present a case of recurrent arteriovenous malformation of the postauricular region in an adolescent male who was taken up for upfront surgical excision with the help of a tumescent solution, thereby eliminating the need for embolisation and drastically reduced intraoperative blood loss.

Radiological Parameters Predicting the Round Window Niche Visibility through Facial Recess Approach in Cochlear Implantation.

Aim: The aim was to study the radiological parameters using High Resolution Computed Tomography (HRCT) temporal bone to predict the Round Window Niche (RWN) visibility through the facial recess approach and to study radiological types of the round window niche. Materials and Methods: Prospective study was done in the patients underwent CI surgery from 2019 to 2021. HRCT radiological parameters of the patients and their intraoperative visualisation from video recordings were compared to predict the most feasible parameters to predict good visualisation of RWN. Results: Among 51 patients (34 males, 17 females) in 48 children round window membrane insertion was done and in three children cochleostomy was done and in two children partial canal wall drilling was done due to poor visualisation of RWN area. Multiple parameters to assess the visibility of the RWN were used. Facial recess width (4.2 mm), location of the mastoid segment of facial nerve (2 mm), external auditory canal to basal turn of cochlea angle (< 13.50) and the radiological types (tunnel shape and semi-circular shape) of the RWN by HRCT were found to be significant parameters in predicting a good visualisation of the RWN. Conclusion: HRCT parameters prepare the surgeon to face the possibility of a difficult surgery and plan to deal with difficult situations. This would eventually lead to better preparedness of surgeons for management of complications.

Correlation of Preoperative Radiological Factors with Histological Involvement of Thyroid Gland in Laryngeal Carcinomas.

Total laryngectomy is the primary treatment for locally advanced laryngeal carcinomas. However, routine thyroid removal (total or hemithyroidectomy) during this procedure is controversial, as the incidence of thyroid gland involvement varies and may lead to lifelong thyroid supplementation, increasing postoperative morbidity. The lack of a consensus on managing the thyroid gland in laryngeal carcinoma cases necessitates improved evaluation techniques, with radiology playing a crucial role in this aspect. Understanding the correlation between radiological factors and histopathological involvement of the thyroid gland can aid in formulating appropriate management strategies during total laryngectomy. To study the correlation of preoperative radiological factors with histopathological involvement of thyroid gland in laryngeal carcinomas. This was a retrospective study which included 57 patients who underwent total laryngectomy for squamous cell carcinoma of larynx. The pre-operative CT findings such as involvement of thyroid cartilage, cricoid cartilage, paraglottic space, anterior commissure, subglottis and thyroid gland along with transglottic extension of tumor were correlated with post-operative histopathological thyroid gland involvement. Cricoid cartilage erosion and thyroid gland involvement in CT scans individually exhibited positive likelihood ratios of 2.58 and 3.23, respectively, demonstrating a reasonable agreement with histopathological findings. The specificity of cricoid cartilage and thyroid gland involvement was also higher with values of 76.4% and 81%, respectively. Moreover, combining thyroid and cricoid cartilage erosion in CT scans as a predictive parameter for thyroid gland involvement resulted in a better likelihood ratio of 8.23 and a fair agreement with histopathological findings. We conclude that cricoid cartilage erosion and thyroid gland involvement in pre-operative CECT can be taken as a preoperative indicator for intraoperative decision on thyroidectomy.

Psychometric properties and factor structure of the suicidal narrative inventory in major depression: A multicentric evaluation.

BACKGROUND: The Suicidal Narrative Inventory (SNI) is a 38-item self-report measure developed to assess elements of the suicidal narrative, a subacute, predominantly cognitive, presuicidal construct. Our objectives were to assess the factor structure, validity, and reliability of the SNI-38 among adults with major depressive disorder (MDD). METHODS: Using a cross-sectional design, we administered the Hindi version of the SNI along with other self-report measures to adults with MDD, recruited from 24 tertiary care hospitals across India. Confirmatory factor analysis (CFA) was performed to assess the factor structure of SNI-38. Reliability (internal consistency) was assessed using Cronbach's alpha (α). Convergent, discriminant, and criterion validity of the SNI-38 were tested by comparing it against other appropriate measures. RESULTS: We collected usable responses from 654 Hindi-speaking participants (Mean age = 36.9 ± 11.9 years, 50.2% female). The eight-factor solution of the SNI showed good model fit indices (χ2[637] = 3345.58, p <.001, CFI =.98, and RMSEA =.08). Internal consistencies for the SNI subscale scores were good to excellent, α ranging from .73 to.92. While most subscales significantly converged with other measures, associations were comparatively weaker and inconsistent for the 'thwarted belongingness' and 'goal reengagement' subscales. CONCLUSION: Consistent with prior data, our study confirmed an eight-factor solution and demonstrated adequate psychometric properties for the Hindi version of the SNI-38 in our sample. These findings provide empirical support for the use of SNI to assess the suicidal narrative among Indian adults with MDD.