Patient Advocates for Clinical Research (PACER): A Step Toward Ethical, Relevant, and Truly Participatory Clinical Research in India.

Background Clinical research presents a promising path for improving healthcare in contemporary India. Yet, researchers identify gaps in trust, awareness, as well as misconceptions about being a '"guinea pig." We proposed building the capacity of training patient advocacy groups (PAGs) in patient-centered clinical research and through them creating aware patients as research partners. Methodology Patient Advocates for Clinical Research (PACER) is a tiered program to share information and education about clinical research with PAGs. Tier one is a self-paced online learning course, followed by workshops on clinical research, Good Clinical Practice, research consent, case studies, and group discussions. Results A total of 20 PAGs represented by 48 participants, active in areas of pediatric cancer, breast cancer, multiple myeloma, type I diabetes, spinal muscular atrophy, sickle cell disease, and inflammatory bowel diseases, participated. Among 48 participants 30 successfully completed the online course (multiple-choice question evaluation score cut-off >70%), attaining an average score of 23.9 ± 2.1 out of 30. Overall, 48 participants attended workshop 1 and 45 workshop 2, with 140 participants joining the focus group discussion (FGD). An overall improvement of 9.4% (𝜒2 = 46.173; p < 0.001) for workshop 1 and 8.2% (𝜒2 = 25.412; p < 0.001) for workshop 2 was seen in knowledge gain about clinical research. The FGD raised issues such as misleading information from research teams, unethical recruitment, incomprehensible information sheets, and limited trial-related knowledge fostering fear of participation in clinical research. Conclusions Multimodal and tiered learning of clinical research such as that used by PACER has a good participatory and learning response from PAGs and may be further explored.

Identification and optimization of pyridine carboxamide-based scaffold as a drug lead for Mycobacterium tuberculosis.

New drugs with novel mechanisms of action are urgently needed to tackle the issue of drug-resistant tuberculosis. Here, we have performed phenotypic screening using the Pathogen Box library obtained from the Medicines for Malaria Venture against Mycobacterium tuberculosis in vitro. We have identified a pyridine carboxamide derivative, MMV687254, as a promising hit. This molecule is specifically active against M. tuberculosis and Mycobacterium bovis Bacillus Calmette-Guérin (M. bovis BCG) but inactive against Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Escherichia coli pathogens. We demonstrate that MMV687254 inhibits M. tuberculosis growth in liquid cultures in a bacteriostatic manner. Surprisingly, MMV687254 was as active as isoniazid in macrophages and inhibited M. tuberculosis growth in a bactericidal manner. Mechanistic studies revealed that MMV687254 is a prodrug and that its anti-mycobacterial activity requires AmiC-dependent hydrolysis. We further demonstrate that MMV687254 inhibits M. tuberculosis growth in macrophages by inducing autophagy. In the present study, we have also carried out a detailed structure-activity relationship study and identified a promising novel lead candidate. The identified novel series of compounds also showed activity against drug-resistant M. bovis BCG and M. tuberculosis clinical strains. Finally, we demonstrate that in contrast to MMV687254, the lead molecule was able to inhibit M. tuberculosis growth in a chronic mouse model of infection. Taken together, we have identified a novel lead molecule with a dual mechanism of action that can be further optimized to design more potent anti-tubercular agents.

Polyphosphate kinase-1 regulates bacterial and host metabolic pathways involved in pathogenesis of Mycobacterium tuberculosis.

Inorganic polyphosphate (polyP) is primarily synthesized by Polyphosphate Kinase-1 (PPK-1) and regulates numerous cellular processes, including energy metabolism, stress adaptation, drug tolerance, and microbial pathogenesis. Here, we report that polyP interacts with acyl CoA carboxylases, enzymes involved in lipid biosynthesis in Mycobacterium tuberculosis. We show that deletion of ppk-1 in M. tuberculosis results in transcriptional and metabolic reprogramming. In comparison to the parental strain, the Δppk-1 mutant strain had reduced levels of virulence-associated lipids such as PDIMs and TDM. We also observed that polyP deficiency in M. tuberculosis is associated with enhanced phagosome-lysosome fusion in infected macrophages and attenuated growth in mice. Host RNA-seq analysis revealed decreased levels of transcripts encoding for proteins involved in either type I interferon signaling or formation of foamy macrophages in the lungs of Δppk-1 mutant-infected mice relative to parental strain-infected animals. Using target-based screening and molecular docking, we have identified raloxifene hydrochloride as a broad-spectrum PPK-1 inhibitor. We show that raloxifene hydrochloride significantly enhanced the activity of isoniazid, bedaquiline, and pretomanid against M. tuberculosis in macrophages. Additionally, raloxifene inhibited the growth of M. tuberculosis in mice. This is an in-depth study that provides mechanistic insights into the regulation of mycobacterial pathogenesis by polyP deficiency.

Glutathione Depletion and Concomitant Elevation of Susceptibility in Patients with Parkinson's Disease: State-of-the-Art MR Spectroscopy and Neuropsychological Study.

Parkinson's disease (PD) is characterized by extrapyramidal motor disturbances and nonmotor cognitive impairments which impact activities of daily living. Although the etiology of PD is still obscure, autopsy reports suggest that oxidative stress (OS) is one of the important factors in the pathophysiology of PD. In the current study, we have investigated the impact of OS in PD by measuring the antioxidant glutathione (GSH) levels from the substantia nigra (SN), left hippocampus (LH) and neurotransmitter γ-amino butyric acid (GABA) levels from SN region. Concomitant quantitative susceptibility mapping (QSM) from SN and LH was also acquired from thirty-eight PD patients and 30 age-matched healthy controls (HC). Glutathione levels in the SN region decreased significantly and susceptibility increased significantly in PD compared to HC. Nonsignificant depletion of GABA was observed in the SN region. GSH levels in the LH region were depleted significantly, but LH susceptibility did not alter in the PD cohort compared to HC. Neuropsychological and physical assessment demonstrated significant impairment of cognitive functioning in PD patients compared to HC. GSH depletion was negatively correlated to motor function performance. Multivariate receiver operating characteristic (ROC) curve analysis on the combined effect of GSH, GABA, and susceptibility in the SN region yielded an improved diagnostic accuracy of 86.1% compared to individual diagnostic accuracy based on GSH (65.8%), GABA (57.5%), and susceptibility (69.6%). This is the first comprehensive report in PD demonstrating significant GSH depletion as well as concomitant iron enhancement in the SN region.

Surgical Outcomes of Endoscopic Versus Conventional Septoplasty.

The most common cause of nasal obstruction is a deviated nasal septum. It causes breathing difficulties and may eventually also cause sinusitis, epistaxis, sleep disturbances and snoring. The traditional surgeries of the nasal septum improve the nasal airway but do not fulfil the essential criteria in most instances. Endoscopic septoplasty is a fast-developing concept and gaining popularity as it provides a direct targeted approach to the septal anatomic deformity allowing a minimally invasive procedure under excellent visualization. The aim of this study is to compare the post-operative morbidity among conventional and endoscopic septoplasty. The present prospective study was conducted on 50 patients having deviated nasal septum. Patients were randomly divided into two groups of 25 each. Out of 50 patients, in 25 patients (Group A) Conventional septoplasty was done, whereas in other 25 patients (Group B) endoscopic septoplasty was done. The patients were followed up post-operatively at 2 weeks, 4 weeks and 8 weeks. Study Design: comparative study. The mean of operating time (min) in Group A was 60.47 ± 8.16 which was significantly higher as compared to Group B (39.7 ± 6.73). (p value < .0001). The Mean of blood loss (mL) was significantly higher in Group A (88.67 ± 8.77) as compared to Group B. (54.6 ± 7.18). (p value < .0001). Post-operative NOSE score at one month was 7.33 ± 1.5 in group A which was significantly higher as compared to Group B (5 ± 1.41). (p value = 0.0007) whereas post-operative NOSE score at 3 months in Group A was 6.53 ± 1.25 which was significantly higher as compared to Group B (4.4 ± 1.78). Proportion of post-operative complications was comparable in Group A and Group B (No complication 80% vs. 92% respectively). According to the present study, both the conventional and endoscopic septoplasty procedures were effective in relieving nasal obstruction in the patients. Endoscopic septoplasty showed significantly better result than conventional septoplasty in terms of time taken for surgery, blood loss during the surgery, post-operative complications and in terms of quality of life as assessed by NOSE Score.

The feasibility of using of a comprehensive unit-based safety program (CUSP) for improving antimicrobial stewardship at a tertiary care hospital in national capital region of India: A prospective quasi experimental study.

PURPOSE: To examine the feasibility of Comprehensive Unit-based Safety Program (CUSP) as a strategy tool to improve antibiotic stewardship in low and middle income countries (LMIC) in resource limited setting. The primary outcome measure is identification of inappropriate prescriptions. The secondary outcome parameters are App adoption trends and antimicrobial prescription pattern and practices. MATERIAL AND METHODS: A prospective quasi-experimental design was used to operationalizing the CUSP intervention. The project considered the data of 482 patients from two mixed Medical ICUs admitted during June 2019 to April 2020. The information was collected on antimicrobials prescription pattern and practices for identification of inappropriate use as well as app adoption trend with respect to Electronic Medical Record (EMR) Orders Placed, Clinical Notes and Checklist Filled. The intervention in the study comprised of development of an antibiotic monitoring stewardship (AMS) data collection app for ease of use and for Clinical Decision Support System (CDSS) to identify the cases of inappropriate use of antibiotics. RESULTS: Data of patients was reviewed to create algorithms for empirical and directed antibiotic therapy as well as to create a CDSS app. Out of 793 prescriptions initially during July-September 2019, 19 (2.4%) were inappropriate antimicrobial prescription. The continuous monitoring of antimicrobial prescription helped in reducing the irrational use and bring it to level zero at the end. CONCLUSION: It requires commitment from the management, and seamless communication within Clinical, Microbiology, Pharmacology and data management teams to create and run a successful CUSP program towards Antimicrobial Resistance. Tools such as the CDSS can smoothen the process.

Evaluation of T and B cell immunophenotyping and antibody response post Covid-19 vaccination.

PURPOSE: To evaluate T and B cell subsets and IgG antibodies in response to SARS-CoV-2 post COVID-19 vaccination. METHODS: A total of 50 healthy adults (18-60 years) receiving anti-SARS-CoV-2 vaccination (COVISHIELD) were recruited for the study. Blood samples were collected from participants at 3 time points; just before vaccination (Visit 0, V0), just before booster dose (Visit 1, V1) and 6th month after 1st dose (Visit 2, V2). Peripheral blood mononuclear cell isolation was done and evaluated for T and B cell subsets by Flow cytometry. Quantitative determination of IgG antibodies to SARS-CoV-2 was done by Chemiluminescence immunoassay in all samples. Final data for all three visits was available for 37 participants who remained healthy. Ethics approval was obtained from Medanta Institution of Ethics Committee vide MICR No. 1290/2021 dated 24th May 2021. RESULTS: Mean age of the participants was 34.6 â€‹± â€‹5.7 years (Range: 24-45 years). Highly significant improvement in SARS-CoV-2 IgG levels was observed after each visit {Mean IgG: (V0 v/s. V1: 133.8 â€‹± â€‹339.2AU/ml v/s. 434.5 â€‹± â€‹519.2AU/ml; p-value â€‹= â€‹0.003) and V0 v/s. V2: 133.8 â€‹± â€‹339.2AU/ml v/s. 420.9 â€‹± â€‹394.2AU/ml; p-value â€‹= â€‹0.002) Between visits 0 and 1, the mean value for CD4 Naïve T cells showed significant increase, while CD4 central memory (CM) T cells showed significant decrease. Between visits 0 and 2 the mean values for CD4 Naïve T cells, CD8 Naïve T cells and Pre germinal centre (Pre GC) B cells showed significant increase. During the same period the mean values for CD4CM, CD8 effector memory (EM) and CD8 CM T cells showed significant decrease. CONCLUSION: It is concluded that both, humoral and cellular immunity, play an important role in maintaining immunity against COVID-19 infection, following COVISHIELD vaccination. Moreover, in subjects with normalisation of antibody levels post vaccination, persistence of T cell subsets may still offer some immunity.

Quantitation of Brain and Blood Glutathione and Iron in Healthy Age Groups Using Biophysical and In Vivo MR Spectroscopy: Potential Clinical Application.

The antioxidant glutathione (GSH) and pro-oxidant iron levels play a balancing role in the modulation of oxidative stress (OS). There is a significant depletion of GSH in the left hippocampus (LH) in patients with Alzheimer's disease (AD) with concomitant elevation of iron level. However, the correlation of GSH and iron distribution patterns between the brain and the peripheral system (blood) is not yet known. We measured GSH and magnetic susceptibility (e.g., iron) in the LH region along with GSH in plasma and iron in serum across four age groups consisting of healthy volunteers (age range 18-72 y, n = 70). We report non-variability of the mean GSH in the plasma and LH region across mentioned age groups. The mean iron level in the LH region does not change, but the iron level in the serum in the 51-72 y age group increases non-significantly. Regression analysis of our data indicated that GSH and iron levels (both in blood and in brain) are not related to age. This research pave the way for the identification of a risk/susceptibility biomarker for AD and Parkinson's disease from the evaluation of GSH (in plasma) and iron (in serum) levels concomitantly.

Role of the Mycobacterium tuberculosis ESX-4 Secretion System in Heme Iron Utilization and Pore Formation by PPE Proteins.

Mycobacterium tuberculosis (Mtb) is transmitted through aerosols and primarily colonizes within the lung. The World Health Organization estimates that Mtb kills ~1.4 million people every year. A key aspect that makes Mtb such a successful pathogen is its ability to overcome iron limitation mounted by the host immune response. In our previous studies, we have shown that Mtb can utilize iron from heme, the largest source of iron in the human host, and that it uses two redundant heme utilization pathways. In this study, we show that the ESX-4 type VII secretion system (T7SS) is necessary for extracellular heme uptake into the Mtb cell through both heme utilization pathways. ESX-4 influences the secretion of the culture filtrate proteins Rv0125 and Rv1085c, which are also necessary for efficient heme utilization. We also discovered that deletion of the alternative sigma factor SigM significantly reduced Mtb heme utilization through both pathways and predict that SigM is a global positive regulator of core heme utilization genes of both pathways. Finally, we present the first direct evidence that some mycobacterial PPE (proline-proline-glutamate motif) proteins of the PPE protein family are pore-forming membrane proteins. Altogether, we identified core components of both Mtb Heme utilization pathways that were previously unknown and identified a novel channel-forming membrane protein of Mtb. IMPORTANCE M. tuberculosis (Mtb) is completely dependent on iron acquisition in the host to cause disease. The largest source of iron for Mtb in the human host is heme. Here, we show that the ancestral ESX-4 type VII secretion system is required for the efficient utilization of heme as a source of iron, which is an essential nutrient. This is another biological function identified for ESX-4 in Mtb, whose contribution to Mtb physiology is poorly understood. A most exciting finding is that some mycobacterial PPE (proline-proline-glutamate motif) proteins that have been implicated in the nutrient acquisition are membrane proteins that can form channels in a lipid bilayer. These observations have far-reaching implications because they support an emerging theme that PPE proteins can function as channel proteins in the outer mycomembrane for nutrient acquisition. Mtb has evolved a heme uptake system that is drastically different from all other known bacterial heme acquisition systems.

Structural and Functional Characterization of Rv0792c from Mycobacterium tuberculosis: Identifying Small Molecule Inhibitor against HutC Protein.

In order to adapt in host tissues, microbial pathogens regulate their gene expression through a variety of transcription factors. Here, we have functionally characterized Rv0792c, a HutC homolog from Mycobacterium tuberculosis. In comparison to the parental strain, a strain of M. tuberculosis with a Rv0792c mutant was compromised for survival upon exposure to oxidative stress and infection in guinea pigs. RNA sequencing analysis revealed that Rv0792c regulates the expression of genes involved in stress adaptation and virulence of M. tuberculosis. Solution small-angle X-ray scattering (SAXS) data-steered model building confirmed that the C-terminal region plays a pivotal role in dimer formation. Systematic evolution of ligands by exponential enrichment (SELEX) resulted in the identification of single-strand DNA (ssDNA) aptamers that can be used as a tool to identify small-molecule inhibitors targeting Rv0792c. Using SELEX and SAXS data-based modeling, we identified residues essential for Rv0792c's aptamer binding activity. In this study, we also identified I-OMe-Tyrphostin as an inhibitor of Rv0792c's aptamer and DNA binding activity. The identified small molecule reduced the growth of intracellular M. tuberculosis in macrophages. The present study thus provides a detailed shape-function characterization of a HutC family of transcription factor from M. tuberculosis. IMPORTANCE Prokaryotes encode a large number of GntR family transcription factors that are involved in various fundamental biological processes, including stress adaptation and pathogenesis. Here, we investigated the structural and functional role of Rv0792c, a HutC homolog from M. tuberculosis. We demonstrated that Rv0792c is essential for M. tuberculosis to adapt to oxidative stress and establish disease in guinea pigs. Using a systematic evolution of ligands by exponential enrichment (SELEX) approach, we identified ssDNA aptamers from a random ssDNA library that bound to Rv0792c protein. These aptamers were thoroughly characterized using biochemical and biophysical assays. Using SAXS, we determined the structural model of Rv0792c in both the presence and absence of the aptamers. Further, using a combination of SELEX and SAXS methodologies, we identified I-OMe-Tyrphostin as a potential inhibitor of Rv0792c. Here we provide a detailed functional characterization of a transcription factor belonging to the HutC family from M. tuberculosis.

Safety, immunogenicity & effectiveness of the COVID-19 vaccine among healthcare workers in a tertiary care hospital.

BACKGROUND & OBJECTIVES: The COVID-19 pandemic has caused significant global morbidity and mortality. As the vaccination was rolled out with prioritization on healthcare workers (HCWs), it was desirable to generate evidence on effectiveness of vaccine in prevailing real-life situation for policy planning. The objective of the study was to evaluate the safety, effectiveness and immunogenicity of COVID-19 vaccination among HCWs in a tertiary care hospital. METHODS: This prospective observational study was undertaken on the safety, immunogenicity and effectiveness of the ChAdOx1 nCoV- 19 coronavirus vaccine (Recombinant) during the national vaccine roll out in January-March 2021, in a tertiary care hospital, New Delhi, India. RESULTS: The vaccine was found to be safe, with local pain, fever and headache as the most common adverse events of milder nature which generally lasted for two days. The adverse events following vaccination were lower in the second dose as compared to the first dose. The vaccine was immunogenic, with seropositivity, which was 51 per cent before vaccination, increasing to 77 per cent after single dose and 98 per cent after two doses. Subgroup analysis indicated that those with the past history of COVID-19 attained seropositivity of 98 per cent even with single dose. The incidence of reverse transcription (RT)-PCR positive COVID-19 was significantly lower among vaccinated (11.7%) as compared to unvaccinated (22.2%). Seven cases of moderate COVID-19 needing hospitalization were seen in the unvaccinated and only one such in the vaccinated group. The difference was significant between the fully vaccinated (10.8%) and the partially vaccinated (12.7%). The hazard of COVID-19 infection was higher among male, age >50 yr and clinical role in the hospital. After adjustment for these factors, the hazard of COVID-19 infection among unvaccinated was 2.09 as compared to fully vaccinated. Vaccine effectiveness was 52.2 per cent in HCWs. INTERPRETATION & CONCLUSIONS: ChAdOx1 nCoV-19 coronavirus vaccine (Recombinant) was safe, immunogenic as well as showed effectiveness against the COVID-19 disease (CTRI/2021/01/030582).

NSC19723, a Thiacetazone-Like Benzaldehyde Thiosemicarbazone Improves the Efficacy of TB Drugs In Vitro and In Vivo.

The complexity and duration of tuberculosis (TB) treatment contributes to the emergence of drug resistant tuberculosis (DR-TB) and drug-associated side effects. Alternate chemotherapeutic agents are needed to shorten the time and improve efficacy of current treatment. In this study, we have assessed the antitubercular activity of NSC19723, a benzaldehyde thiosemicarbazone molecule. NSC19723 is structurally similar to thiacetazone (TAC), a second-line anti-TB drug used to treat individuals with DR-TB. NSC19723 displayed better MIC values than TAC against Mycobacterium tuberculosis and Mycobacterium bovis BCG. In our checkerboard experiments, NSC19723 displayed better profiles than TAC in combination with known first-line and recently approved drugs. Mechanistic studies revealed that NSC19723 inhibits mycolic acid biosynthesis by targeting the HadABC complex. Computational studies revealed that the binding pocket of HadAB is similarly occupied by NSC19723 and TAC. NSC19723 also improved the efficacy of isoniazid in macrophages and mouse models of infection. Cumulatively, we have identified a benzaldehyde thiosemicarbazone scaffold that improved the activity of TB drugs in liquid cultures, macrophages, and mice. IMPORTANCE Mycobacterium tuberculosis, the causative agent of TB is among the leading causes of death among infectious diseases in humans. This situation has worsened due to the failure of BCG vaccines and the increased number of cases with HIV-TB coinfections and drug-resistant strains. Another challenge in the field is the lengthy duration of therapy for drug-sensitive and -resistant TB. Here, we have deciphered the mechanism of action of NSC19723, benzaldehyde thiosemicarbazone. We show that NSC19723 targets HadABC complex and inhibits mycolic acid biosynthesis. We also show that NSC19723 enhances the activity of known drugs in liquid cultures, macrophages, and mice. We have also performed molecular docking studies to identify the interacting residues of HadAB with NSC19723. Taken together, we demonstrate that NSC19723, a benzaldehyde thiosemicarbazone, has better antitubercular activity than thiacetazone.

HupB, a nucleoid-associated protein, is critical for survival of Mycobacterium tuberculosis under host-mediated stresses and for enhanced tolerance to key first-line antibiotics.

To survive and establish its niche, Mycobacterium tuberculosis (Mtb) engages in a steady battle against an array of host defenses and a barrage of antibiotics. Here, we demonstrate that Mtb employs HupB, a nucleoid-associated protein (NAP) as its key player to simultaneously battle and survive in these two stress-inducing fronts. Typically, NAPs are key to bacterial survival under a wide array of environmental or host-mediated stresses. Here, we report that for Mtb to survive under different macrophage-induced assaults including acidic pH, nutrient depletion, oxidative and nitrosative stresses, HupB presence is critical. As expected, the hupB knockout mutant is highly sensitive to these host-mediated stresses. Furthermore, Mtb aptly modulates HupB protein levels to overcome these stresses. We also report that HupB aids Mtb to gain tolerance to high levels of rifampicin (RIF) and isoniazid (INH) exposure. Loss of hupB makes Mtb highly susceptible to even short exposures to reduced amounts of RIF and INH. Overexpressing hupB in Mtb or complementing hupB in the hupB knockout mutant triggers enhanced survival of Mtb under these stresses. We also find that upon loss of hupB, Mtb significantly enhances the permeability of its cell wall by modulating the levels of several surface lipids including phthiocerol dimycocerosates (PDIMs), thus possibly influencing overall susceptibility to host-mediated stresses. Loss of hupB also downregulates efflux pump expression possibly influencing increased susceptibility to INH and RIF. Finally, we find that therapeutic targeting of HupB with SD1, a known small molecule inhibitor, significantly enhances Mtb susceptibility to INH and THP-1 macrophages and significantly reduces MIC to INH. Thus, our data strongly indicate that HupB is a highly promising therapeutic target especially for potential combinatorial shortened therapy with reduced INH and RIF doses.

Design and synthesis of benzimidazole derivatives as antimycobacterial agents.

A series of 2,5-disubstituted benzimidazole derivatives was synthesized with the aim to identify compounds with potent anti-TB activity. All the compounds were screened in vitro against cultured Mycobacterium tuberculosis H37 Rv strain and found to be exhibiting MIC99 values in the range of 0.195-100 µM. Out of 43 synthesized compounds, two compounds 11h and 13e showed better anti-TB activity than the reference drug isoniazid.

Seroprevalence of Covid-19 infection among healthcare workers: A study from a tertiary care hospital in the National Capital Region of India.

Background Seroprevalence studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can provide information on the target populations for vaccination. We aimed to evaluate the seroprevalence among healthcare workers (HCWs) at our tertiary care institution and to identify parameters that may affect it. Method We assessed seroprevalence of SARS-CoV-2 by the chemiluminescence immunoassay test among 3258 HCW in our hospital and evaluated as per gender, age, their previous Covid-19 diagnosis, role in hospital and type/risk of exposure. Results Of 3258 participants, 46.2% (95% CI 44.4%- 47.9%) were positive for SARS-CoV-2 IgG antibodies (i.e. IgG ≥15 AU/ml). Higher seroprevalence was seen in non-clinical HCWs (50.2%) than in clinical HCWs (41.4%, p=0.0001). Furthermore, people with a history of Covid-19 were found to have significantly higher antibody levels (p=0.0001). Among the HCWs, doctors and nurses had lower relative risk (RR) of acquiring Covid-19 infection (RR=0.82; 95% CI 0.76-0.89) compared to non-clinical HCWs. Conclusion Seroprevalence in HCWs at our hospital was 46.2%. Clinical HCWs had lower seroprevalence compared to non-clinical HCWs. Previous history of Covid-19 almost doubled the seropositivity, particularly in those with current infection.

Global Hunger Index does not really measure hunger - An Indian perspective.

The Global Hunger Index (GHI) is calculated and disseminated annually. India, which is the 5th largest economy in the world and has a good ranking in many other indicators, has a poor ranking based on this index. After a critical review of the appropriateness of the indicators used in GHI, the Indian Council of Medical Research has the viewpoint that the indicators of undernourishment, stunting, wasting and child mortality do not measure hunger per se. Referring to this index as a Hunger Index, and thereby ranking countries is not appropriate, since many of the measures that are used to evolve an index that measures hunger are probably contextual. Countries should therefore evolve their own measures that are suitable for their own context.

Determination of Role of Type 16 Human Papillomavirus and Risk Factors in Assessing Oropharyngeal Cancer Survival.

BACKGROUND: It is ascertained that the survival rate of patients infected with type 16 human papillomavirus (HPV16) positive is better as compared to those infected with HPV16 negative. The present study was conducted to determine rgw role of HPV16 and risk factors in assessing oropharyngeal cancer (OPC) death. METHODOLOGY: A total of 102 clinically and histologically proven cases of oral pharyngeal cancer were included. Seropositivity for HPV16 E6 as a marker of HPV16-positive cancer was estimated. RESULTS: Out of 102 patients, there were 70 males and 32 females. Significant risk factors associated with OPC survival overall in the univariate analysis was female sex (hazard ratio [HR] 0.54, 95% confidence level [CL]: 0.36-80), alcohol use >2 drinks/day (HR 1.54, 95% CL: 1.12-2.08), smoking >10 pack-years (HR 2.20, 95% CL: 1.42-3.58), moderate dental (HR 1.54, 95% CL: 1.02-2.32), underweight (HR 2.24, 95% CL: 1.34-3.60), and Stage IV cancer (HR 2.82, 95% CL: 1.76-4.40). There was significant low risk for death among HPV16 positive (HR 0.48, 95% CL: 0.32-0.70). CONCLUSION: HPV16 status is an independent prognostic factor for OPC deaths. The common risk factors were female gender, moderate oral care, underweight body mass index, excessive alcohol, and smoking tobacco.

Assessment of Effect of Menopause on Saliva and Oral Health Status.

BACKGROUND: Women at menopausal period may frequently develop several oral mucosal disorders. Xerostomia is also a common finding among postmenopausal women. The present study was conducted to assess effect of menopause on saliva and dental health. MATERIALS AND METHODS: Forty postmenopausal women (Group I) and 40 control (Group II) underwent Oral Hygiene Index Simplified (OHIS), Decayed, Missing and Filled Teeth (DMFT index), Community periodontal index (CPI), and Loss of attachment (LOA), salivary pH and flow measurement. RESULTS: Oral symptoms were normal in 22 and 40, xerostomia in 18 and 0 in Group I and II respectively, salivary pH was normal in 20 and 40, below acidic in 20 and 0, salivary flow was normal in 21 and 40, hyposalivation in 19 and 0 in group I and II, respectively. The difference was significant (P < 0.05). OHI-S was good in 4 and 25, fair in 6 and 10, poor in 30 and 5, DMFT index was decayed was 1.42 and 0.65, missing was 2.84 and 0.26 and filled was 1.06 and 0.52 seen in Group I and II respectively. CPI index mean value was 3.26 in Group I and 1.02 in Group II and mean LOA was 1.42 and 0.46 in Group I and II respectively. The difference was significant (P < 0.05). CONCLUSION: There was decrease in the salivary pH and flow rate in postmenopausal women which in turn leads to increased OHI-S, DMFT, CPI, and LOA.