Unveiling the Neurotoxicity of Metronidazole: A Clinical Conundrum.

Metronidazole, a commonly used antiprotozoal agent, has been linked to neurotoxicity in a few individuals. We present the case of a 61-year-old gentleman diagnosed with a liver abscess, who received a total dose of 64 g of metronidazole over a four-week duration. He subsequently developed slurred speech, numbness, and tingling sensation in both feet. His neuroimaging revealed T2 hyperintensities in the bilateral dentate nuclei and withdrawal of the drug led to symptomatic improvement in the patient. Metronidazole is known to produce neurological manifestations with involvement of peripheral nerves and cerebellum commonly. In the present case, the cumulative dose impact of metronidazole on the dentate nucleus was evident.

Utility of Indigenous Cytology Technique in the Diagnosis of Oral Cavity Lesions using Normal Saline as a Processing Fluid: A Comparative Study.

Background: Oral cancer is a major health problem in developing countries. Cytology has been widely accepted as a tool in the early diagnosis of cancer. Objectives: To evaluate the diagnostic utility of four different cytology techniques, that is, modified brush cytology (BR) technique, brush cytology cytocentrifugation (BRCC) technique, modified scrape cytology (SR) technique, and scrape cytology cytocentrifugation (SRCC) technique and correlate the cytopathological diagnosis with the available histopathological diagnosis. Materials and Methods: It was a prospective observational study of oral cavity lesions conducted from January 2018 to December 2018 at a rural tertiary care referral institute. Smears prepared by four different techniques, that is, BR technique, BRCC technique, SR technique and SRCC technique were evaluated using a scoring system. Normal saline was used as a processing fluid for cytocentrifugation techniques, and the cytological diagnosis was compared with an available histopathological diagnosis for concordance. Results: Twenty-seven cases of oral cavity lesions were analyzed. Squamous cell carcinoma (55.56%) constituted the most common lesion diagnosed by cytology. Total concordance was 95.65%. Brush cytology techniques were better technique than scrape cytology techniques. Cytocentrifugation techniques were better than modified brush cytology technique and modified scrape cytology technique and the values were statistically highly significant (P<0.0001). Conclusion: The utility of only normal saline as a processing fluid for cytocentrifugation may be considered an unexplored and prudent endeavor. This indigenously designed technique may be employed to improve the quality of cytological preparation for the evaluation of oral cavity lesions.

A comparative study on perception and use of generic drugs between public and private health practitioners.

Context: The perception of generic drugs may vary significantly between government and private doctors because physicians in the private sector have more prescribing choices and flexibility. Hence, this study was undertaken to analyse the knowledge, attitude and perception (KAP) of government and private physicians on generic drugs. Materials and Methods: This was a questionnaire-based cross-sectional study conducted among physicians working in public and private health sectors. The questionnaire had 25 closed-ended questions related to the KAP of generic medicine. The overall scores were categorised using Bloom's cut-off point. The Chi-square or Mann-Whitney U-test was used to compare the differences between the two groups. Results: About 80% of the participants in both groups agreed that generic medicines contain the same active ingredients as brand-name drugs, are less expensive and are available in the Indian market. Nearly 84% of government physicians and only 64% of private physicians believed that generic medicines are just as effective and secure as branded medicines (P - 0.003). The majority of physicians from both groups concurred that there is a lack of quality check in generic drug manufacturing, and they require more information about bioequivalence studies. In both categories, about 75% of participants preferred generic medications for their patients. However, in both groups, more than 50% of physicians were concerned about therapeutic failure and expressed reluctance to prescribe generic medications in life-threatening situations. Conclusions: Knowledge and acceptance of generic drugs regarding efficacy, safety, bioequivalence and therapeutic failure are low among both government and private physicians.

Cost of National Vector Borne Disease Control Programme in North India.

Background & objectives: Despite significant resources being spent on National Vector Borne Disease Control Programme (NVBDCP), there are meagre published data on health system cost upon its implementation. Hence, the present study estimated the annual and unit cost of different services delivered under NVBDCP in North India. Methodology: Economic cost of implementing NVBDCP was estimated based on data collected from three North Indian States, i.e. Punjab, Haryana and Himachal Pradesh. Multistage stratified random sampling was used for selecting health facilities across each level [i.e. subcentres (SCs), Primary Health Centres (PHCs), community health centres (CHCs) and district malaria office (DMO)] from the selected States. Data on annual consumption of both capital and recurrent resources were assessed from each of the selected facilities following bottom-up costing approach. Capital items (equipment, vehicles and furniture) were annualized over average life span using a discount rate of 3 per cent. The mean annual cost of implementation of NVBDCP was estimated for each level along with unit cost. Results: The mean annual cost of implementing NVBDCP at the level of SC, PHC and CHC and DMO was ₹ 230,420 (199,523-264,901), 686,962 (482,637-886,313), 1.2 million (0.9-1.5 million) and 9.1 million (4.6-13.5 million), respectively. Per capita cost for the provision of complete package of services under NVBDCP was ₹ 45 (37-54), 48 (29-73), 10 (6-14) and 47 (31-62) at the level of SC, PHC, CHC and DMO level, respectively. The per capita cost was higher in Himachal Pradesh (HP) at SC [₹ 69 (52-85)] and CHC [₹ 20.8 (20.7-20.8)] level and in Punjab at PHC level [₹ 89 (49-132)] as compared to other States. Interpretation & conclusions: The evidence on cost of NVBDCP can be used to undertake future economic evaluations which could serve as a basis for allocating resources efficiently, policy development as well as future planning for scale up of services.

Clinical characteristics & outcome of SARS-CoV-2 infected neonates presenting to paediatric emergency.

Background & objectives: Data on neonatal COVID-19 are limited to the immediate postnatal period, with a primary focus on vertical transmission in inborn infants. This study was aimed to assess the characteristics and outcome of COVID-19 in outborn neonates. Methods: All neonates admitted to the paediatric emergency from August 1 to December 31, 2020, were included in the study. SARS-CoV-2 reverse transcription- (RT)-PCR test was done on oro/nasopharyngeal specimens obtained at admission. The clinical characteristics and outcomes of SARS-CoV-2 positive and negative neonates were compared and the diagnostic accuracy of a selective testing policy was assessed. Results: A total of 1225 neonates were admitted during the study period, of whom SARS-CoV-2 RT-PCR was performed in 969. The RT-PCR test was positive in 17 (1.8%). Mean (standard deviation) gestation and birth weight of SARS-CoV-2-infected neonates were 35.5 (3.2) wk and 2274 (695) g, respectively. Most neonates (11/17) with confirmed COVID-19 reported in the first two weeks of life. Respiratory distress (14/17) was the predominant manifestation. Five (5/17, 29.4%) SARS-CoV-2 infected neonates died. Neonates with COVID-19 were at a higher risk for all-cause mortality [odds ratio (OR): 3.1; 95% confidence interval (CI): 1.1-8.9, P=0.03]; however, mortality did not differ after adjusting for lethal malformation (OR: 2.4; 95% CI: 0.7-8.7). Sensitivity, specificity, accuracy, positive and negative likelihood ratios (95% CI) of selective testing policy for SARS-CoV-2 infection at admission was 52.9 (28.5-76.1), 83.3 (80.7-85.6), 82.8 (80.3-85.1), 3.17 (1.98-5.07), and 0.56 (0.34-0.93) per cent, respectively. Interpretation & conclusions: SARS-CoV-2 positivity rate among the outborn neonates reporting to the paediatric emergency and tested for COVID-19 was observed to be low. The selective testing policy had poor diagnostic accuracy in distinguishing COVID-19 from non-COVID illness.

Diversity in HIV epidemic transitions in India: An application of HIV epidemiological metrices and benchmarks.

BACKGROUND: The Joint United Nations Programme on AIDS (UNAIDS) has emphasized on the incidence-prevalence ratio (IPR) and incidence-mortality ratio (IMR) to measure the progress in HIV epidemic control. In this paper, we describe the status of epidemic control in India and in various states in terms of UNAIDS's recommended metrices. METHOD: The National AIDS Control Programme (NACP) of India spearheads work on mathematical modelling to estimate HIV burden based on periodically conducted sentinel surveillance for providing guidance to program implementation and policymaking. Using the results of the latest round of HIV Estimations in 2019, IPR and IMR were calculated. RESULTS: National level IPR was 0.029 [0.022-0.037] in 2019 and ranged from 0.01 to 0.15 in various States and Union Territories (UTs). Corresponding Incidence-Mortality Ratio was at 0.881 [0.754-1.014] nationally and ranged between 0.20 and 12.90 across the States/UTs. CONCLUSIONS: Based on UNAIDS recommended indicators for HIV epidemic control, namely IPR and IMR; national AIDS response in India appears on track. However, the program success is not uniform and significant heterogeneity as well as expanding epidemic was observed at the level of States or UTs. Reinforcing States/UTs specific and focused HIV prevention, testing and treatment initiatives may help in the attainment of 2030 Sustainable Development Goals of ending AIDS as a public health threat by 2030.

In silico multi-epitope Bunyumwera virus vaccine to target virus nucleocapsid N protein.

BACKGROUND: Bunyumwera virus can cause 82% mortality in humans currently with no vaccine or drugs for treatment. We described an in silico multi-epitope vaccine targeting Bunyumwera virus nucleocapsid N-protein and predicted B and T cell epitopes for immunogenicity, allergenicity, toxicity, and conservancy. For creating the most potent immunological response possible, docking epitopes with HLA alleles are chosen to screen them. The 3D vaccination was docked with the Toll-like receptor-8 using molecular dynamic simulations. To ensure production efficiency, the vaccine sequence was further cloned in silico in a plasmid pIB2 vector. For efficacy and safety, results must be supported in vitro and in vivo. RESULTS: The vaccine was cloned to enable expression and translation in a plasmid vector pIB2. It was expected to be antigenic, non-allergenic, and have a high binding affinity with TLR-8 in silico cloning. This multi-epitope vaccination may stimulate both innate and adaptive immunity. CONCLUSION: The vaccine developed in this work was based on the nucleocapsid N-protein of the Bunyumwera virus and was created using a reverse vaccinology method. Further experimental validation is required to assess the vaccine's therapeutic effectiveness and immunogenicity.

Comparison of prevention of parent-to-child HIV transmission programme & national biennial HIV sentinel surveillance data for tracking HIV epidemic in India.

Background & objectives: HIV sentinel surveillance (HSS) among antenatal women in India has been used to track the epidemic for many years. However, reliable tracking at the local level is not possible as ANC sentinel sites are limited in number and cover a smaller sample size at each site. Prevention of parent-to-child-transmission (PPTCT) programme data has a potential advantage due to better geographical coverage, which could provide more precise HIV case estimates; therefore, we compared HSS ANC data with PPTCT programme data for HIV tracking. Methods: Out of the 499 surveillance sites, where HSS and PPTCT programme was being conducted in 2015, 210 sites (140 urban and 70 rural) were selected using a stratified random sampling method. HSS (n=72,981) and PPTCT (n=112,832) data records were linked confidentially. The sociodemographic characteristics of HSS and PPTCT attendees were compared. HIV prevalence from HSS ANC was compared with the PPTCT programme data using Chi-square test. State- and site-level correlation of HIV prevalence was also done. Concordance between HSS and PPTCT HIV positivity was estimated using kappa statistics. Results: The age distribution of HSS and PPTCT attendees was similar (range: 23 to 27 yr); however, HSS ANC participants were better educated, whereas PPTCT recorded a higher proportion of homemakers. The correlation of HIV prevalence between HSS and PPTCT was high (r=0.9) at the State level and moderate at the site level (r=0.7). The HIV positivity agreement between HSS ANC and PPTCT was good (kappa=0.633). A similar prevalence was reported across 26 States, whereas PPTCT had a significantly lower prevalence than HSS in three States where PPTCT coverage was low. Overall HIV prevalence was 0.31 per cent in HSS and 0.22 per cent in PPTCT (P<0.001). Interpretation & conclusions: High-quality PPTCT programme data can provide reliable HIV trends in India. An operational framework for PPTCT-based surveillance should be pilot-tested in a phased manner before replacing HSS with PPTCT.

Exploring the role of bacillus calmette-guerin vaccination in protection against COVID-19.

BACKGROUND: In recent studies, it has been established that countries having Bacillus Calmette-Guerin (BCG) vaccination programs reported less COVID-19 cases and deaths per population Preliminary studies suggest that BCG vaccination could upregulate the vaccine-induced immunity against SARS-CoV-2. Hence, the recent study was aimed to determine the association of BCG vaccine with the development of COVID-19 in health care workers. METHODS: The participants included in the study were healthcare workers (doctors, paramedics, and other supporting staff) working in the high and low-risk zones of COVID-19 in the hospital. The Graph Pad statistical analysis tool was used to determine the association of preliminary BCG vaccination with their COVID-19 status. RESULTS: A total of 200 health care workers working in different departments of the hospital were enrolled in the study. The relative risk of COVID-19 positivity in BCG vaccinated versus unvaccinated was 0.79 (0.50-1.25). There was also a significant negative correlation between two groups. The relative risk of COVID-19 positivity in those with a BCG scar was 0.63 (0.44-0.92). The relative risk of COVID-19 infection in those with a history of tuberculosis was 1.08 (0.56-2.09). CONCLUSION: The present study did not support the beneficial effect of BCG vaccine in protection against the development of COVID-19 disease.

Comparative performance of verbal autopsy methods in identifying causes of adult mortality: A case study in India.

Background & objectives: Cause of death assignment from verbal autopsy (VA) questionnaires is conventionally accomplished through physician review. However, since recently, computer softwares have been developed to assign the cause of death. The present study evaluated the performance of computer software in assigning the cause of death from the VA, as compared to physician review. Methods: VA of 600 adult deaths was conducted using open- and close-ended questionnaires in Nandpur Kalour Block of Punjab, India. Entire VA forms were used by two physicians independently to assign the cause of death using the International Statistical Classification of Diseases and Related Health Problems (ICD)-10 codes. In case of disagreement between them, reconciliation was done, and in cases of persistent disagreements finally, adjudication was done by a third physician. InterVA-4-generated causes from close-ended questionnaires were compared using Kappa statistics with causes assigned by physicians using a questionnaire having both open- and close-ended questions. At the population level, Cause-Specific Mortality Fraction (CSMF) accuracy and P-value from McNemar's paired Chi-square were calculated. CSMF accuracy indicates the absolute deviation of a set of proportions of causes of death out of the total number of deaths between the two methods. Results: The overall agreement between InterVA-4 and physician coding was 'fair' (κ=0.42; 95% confidence interval 0.38, 0.46). CSMF accuracy was found to be 0.71. The differences in proportions from the two methods were statistically different as per McNemar's paired Chi-square test for ischaemic heart diseases, liver cirrhosis and maternal deaths. Interpretation & conclusions: In comparison to physicians, assignment of causes of death by InterVA- 4 was only 'fair'. Hence, it may be appropriate to continue with physician review as the optimal option available in the current scenario.

Increased prolidase activity in Alzheimer's dementia: A case-control study.

Prolidase enzyme, which catalyzes the final step in collagen metabolism can influence the cognitive functions through changes in extracellular matrix (ECM) resulting in altered synaptic connectivity in Alzheimer's disease (AD). In this study, it was found that the prolidase activity was significantly higher (p = 0.0016) in AD subjects (5.62 ± 2.05 U/ mL) than control group (4.45 ± 0.92 U/ mL). The increase was significant beginning at mild AD (p = 0.006) with an inverse correlation with HMSE scores (p = 0.0344), thus implying that prolidase mediated alterations in ECM may be associated with the cognitive deficits seen in AD.

Selective Induction of Cellular Toxicity and Anti-tumor Efficacy by N-Methylpiperazinyl Diarylidenylpiperidone and its Pro-nitroxide Conjugate through ROS-mediated Mitochondrial Dysfunction and G2/M Cell-cycle Arrest in Human Pancreatic Cancer.

Pancreatic adenocarcinoma is an aggressive cancer with poor clinical prognosis and limited therapeutic options. There is a significant lack of effective, safe, and targeted therapies for successful treatment of pancreatic cancer. In this report, we describe the anticancer efficacy of two novel compounds, N-methylpiperazinyl diarylidenylpiperidone (L-2663) and its pro-nitroxide conjugate (HO-4589) evaluated on human pancreatic adenocarcinoma (AsPC-1) cell line and xenograft tumor in mice. Using flow cytometry, we determined the effect of the L-2663 and HO-4589 drugs in inducing mitochondrial toxicity, triggering cell-cycle arrest, and apoptosis. EPR spectroscopy was used to quantify cellular uptake, metabolic conversion and stability of HO-4589 in cells and in vivo monitoring of tumor oxygenation as a function of growth. The results established different antiproliferative efficacy of the L-2663 and HO-4589 compounds, with a targeted action on cancer cells while being less toxic to noncancerous cells. The study may have important implications in the future designs of safe and effective chemotherapeutic agents for the treatment of pancreatic cancer.

Effect of Biohythane Production from Distillery Spent Wash with Addition of Landfill Leachate and Sewage Wastewater.

Rapid development of the industrial and domestic sectors has led to the rise of several energy and environmental issues. In accordance with sustainable development and waste minimization issues, biohydrogen production along with biomethane production via two-stage fermentation process using microorganisms from renewable sources has received considerable attention. In the present study, biohythane production with simultaneous wastewater treatment was studied in a two-stage (Biohydrogen and Biomethane) fermentation process under anaerobic conditions. Optimization of high organic content (COD) distillery spent wash effluent (DSPW) with dilution using sewage wastewater was carried out. Addition of leachate as a nutrient source was also studied for effective biohythane production. The experimental results showed that the maximum biohythane production at optimized concentration (substrate concentration of 60 g/L with 30% of leachate as a nutrient source) was 67 mmol/L bio-H2 and with bio-CH4 production of 42 mmol/L. Graphical Abstract.

Antiproliferative Effect of a Novel 4,4'-Disulfonyldiarylidenyl Piperidone in Human Colon Cancer Cells.

The synthesis and antiproliferative effect of a novel curcumin analog, 4,4'-disulfonyldiarylidenyl piperidone, are reported. The design of the molecule is based on the fusion of an antiproliferative segment, namely diarylidenyl piperidone (DAP), with N-hyroxypyrroline, which is known to metabolically convert to nitroxide and protect healthy cells. Cellular uptake, metabolic conversion, cytotoxicity and antiproliferative effect of the DAP derivative against HCT-116 human colon cancer cells have been determined. Based on cell viability and proliferation assays as well as western-blot analysis of major transcription factors and inhibitory proteins, it is determined that the DAP compound is cytotoxic by inhibiting cell survival and proliferation pathways. The findings may have important implications in the design and development of effective anticancer agents.

Copper Catalyzed C-H Activation.

Activation of C-H bonds and their application in cross coupling chemistry has received a wider interest in recent years. The conventional strategy in cross coupling reaction involves the pre-functionalization step of coupling reactants such as organic halides, pseudo-halides and organometallic reagents. The C-H activation facilitates a simple and straight forward approach devoid of pre-functionalization step. This approach also addresses the environmental and economical issues involved in several chemical reactions. In this account, we have reported C-H bond activation of small organic molecules, for example, formamide C-H bond can be activated and coupled with ß-dicarbonyl or 2-carbonyl substituted phenols under oxidative conditions to yield carbamates using inexpensive copper catalysts. Phenyl carbamates were successfully synthesized in moderate to good yields by cross dehydrogenative coupling (CDC) of phenols with formamides using copper catalysts in presence of a ligand. We have also prepared unsymmetrical urea derivatives by oxidative cross coupling of formamides with amines using copper catalysts. Synthesis of N,N-dimethyl substituted amides, 5-substituted-γ-lactams and α-acyloxy ethers was carried out from carboxylic acids using recyclable CuO nanoparticles. Copper nanoparticles afforded N-aryl-γ-amino-γ-lactams by oxidative coupling of aromatic amines with 2-pyrrolidinone. Reusable transition metal HT-derived oxide catalyst was used for the synthesis of N,N-dimethyl substituted amides by the oxidative cross-coupling of carboxylic acids and substituted benzaldehydes. Overview of our work in this area is summarized.

A removable functional group strategy for regiodivergent Wittig rearrangement products.

[1,2] and [2,3] Wittig rearrangements are competing reaction pathways, often leading to uncontrollable product distribution. We employ a single removable functional group to fulfill the dual role of attaining a reversible [2,3] and stabilizing radical intermediate for the [1,2] path to obtain both the Wittig products selectively for a broad range of substrates.

Supplemental Oxygen Protects Heart Against Acute Myocardial Infarction.

Myocardial infarction (MI), which occurs often due to acute ischemia followed by reflow, is associated with irreversible loss (death) of cardiomyocytes. If left untreated, MI will lead to progressive loss of viable cardiomyocytes, deterioration of cardiac function, and congestive heart failure. While supplemental oxygen therapy has long been in practice to treat acute MI, there has not been a clear scientific basis for the observed beneficial effects. Further, there is no rationale for the amount or duration of administration of supplemental oxygenation for effective therapy. The goal of the present study was to determine an optimum oxygenation protocol that can be clinically applicable for treating acute MI. Using EPR oximetry, we studied the effect of exposure to supplemental oxygen cycling (OxCy) administered by inhalation of 21-100% oxygen for brief periods (15-90 min), daily for 5 days, using a rat model of acute MI. Myocardial oxygen tension (pO2), cardiac function and pro-survival/apoptotic signaling molecules were used as markers of treatment outcome. OxCy resulted in a significant reduction of infarct size and improvement of cardiac function. An optimal condition of 30-min OxCy with 95% oxygen + 5% CO2 under normobaric conditions was found to be effective for cardioprotection.