Immunogenicity, clinical efficacy and safety of additional second COVID-19 booster vaccines against Omicron and its subvariants: A systematic review.

The Omicron variant of severe acute respiratory syndrome coronavirus 2 is a new variant of concern (VOC) and an emerging subvariant that exhibits heightened infectivity, transmissibility, and immune evasion, escalating the incidence of moderate to severe coronavirus disease 2019 (COVID-19). It resists monoclonal antibodies and diminishes vaccine efficacy. Notably, new sublineages have outpaced earlier predominant sublineages. Although the primary vaccination series and initial boosters were robust against previous VOCs, their efficacy waned against Omicron and its subvariants. In this systematic review, we assessed real-world evidence on the immunogenicity, clinical efficacy, and safety of a second booster or fourth COVID-19 vaccine dose against the Omicron VOC and its subvariants. A comprehensive literature search was conducted in Medline/PubMed, Google Scholar, bioRxiv, and medRxiv, and relevant studies published between 2022 and 30 May 2023 were reviewed. We found a total of 40 relevant articles focusing on a second booster dose for COVID-19, including clinical trials and observational studies, involving 3,972,856 patients. The results consistently revealed that an additional second booster dose restored and prolonged waning immunity, activating both humoral and cellular responses against Omicron and its subvariants. A second booster treatment correlated with enduring protection against COVID-19, notably preventing substantial symptomatic disease and mortality associated with severe Omicron infection. Both monovalent messenger RNA (mRNA) and nonmRNA vaccines demonstrated similar efficacy and safety, with bivalent mRNA vaccines exhibiting broader protection against emerging subvariants of Omicron. The safety profiles of second booster were favourable with only mild systemic and local symptoms reported in some recipients. In conclusion, this systematic review underscores the additional COVID-19 vaccine boosters, particularly with bivalent or multivalent mRNA vaccines, for countering the highly infectious emerging subvariants of Omicron.

Examining the association between perceived stigma, its correlates, and restrictions in participation among persons with disabilities in Nepal: a cross-sectional study.

BACKGROUND: Disability stigma in low- and middle-income countries is one of the most persistent and complex barriers limiting persons with disabilities (PwDs) from enjoying their rights and opportunities. Perceived stigma among PwDs and its impact on participation restriction is rarely assessed in Nepal. OBJECTIVE: This study aimed to measure the extent of perceived stigma by PwDs, identify its relationships with specific demographic factors, and assess the impact on social participation. METHODS: A cross-sectional survey was conducted between May and July 2022 among PwDs in Nepal, with a sample of 371. The Explanatory Model Interview Catalog (EMIC) stigma scale and P-scale suitable for people affected by stigmatized conditions were used, and the generated scores were analyzed. One-way ANOVA was performed to determine group differences for sociodemographic variables, and linear regression and correlational analysis were used to identify their association and measure the strength and direction of the relationship. RESULTS: The mean stigma score was 16.9 (SD 13.8). 42% of respondents scored higher than the mean. The scores differed significantly by disability type, caste and ethnicity, education, occupation, and household wealth. Over 56% reported participation restriction, and 38% had severe/extreme restriction. Approximately 65% of participants with intellectual disabilities, 53% with multiple disabilities, and 48.5% of persons with severe or profound disabilities experienced severe or extreme restrictions. Perceived stigma had a positive correlation with Disability type (r = 0.17, P < 0.01) and negative correlations with Severity of disability (r= -0.15, P < 0.05), and Household wealth (r= -0.15, P < 0.01). Education was inversely associated with both stigma (r= -0.24, P < 0.01), and participation restriction (ß= -9.34, P < 0.01). However, there was no association between stigma and participation restriction (ß= -0.10, P > 0.05). CONCLUSION: All participants exhibited stigma in general; however, the severity varied based on disability type, level of education, and sociocultural circumstances. A large proportion of participants reported facing a high degree of restrictions in participation; however, no association was detected between perceived stigma and participation restriction. A significant negative linear correlation was observed between education and participation restriction. Stigma reduction programs focusing on education and empowerment would be especially important for overcoming internalized stigma and increasing the participation of PwDs.

IL-18 Gene Promoter Polymorphisms are Involved in Periodontal Disease: A Meta-Analysis.

Microbial plaque that builds up in the gingival crevice area causes inflammation and leads to periodontal disease. Previous research has shown an association between interleukins with periodontitis. The association between interleukin-18 (IL-18) gene polymorphism and periodontitis risk was studied extensively, but the results are contradictory. The aim of this study is to find the association of two IL-18 promoter variants namely -607 C > A (rs1946518) and -137 G > C (rs187238), and the risk of chronic and aggressive periodontal disease by meta-analysis. The databases of PubMed, Medline, Web of Science, and Google Scholar were all explored to find the appropriate studies. The MetaGenyo software was used to calculate each analysis. Outcomes of the pooled analyses revealed significantly elevated risk for periodontitis for both polymorphisms. There is no significant heterogeneity between studies. No significant publication bias was observed. This meta-analysis provided the evidence of a link between IL-18 gene polymorphism in periodontitis.

Role of CD4+ T Cells in Parkinson's Disease.

Parkinson's disease (PD) is a progressive condition that affects both the central nervous system and other body parts that are controlled by the nervous system. PD is characterized by brain dopaminergic neurons loss and, at present, there are only symptomatic treatments available to alleviate the effects of the disease. With extensive research, new insights have led to defining PD as a multi-system disorder with immune dysfunction playing a dominant part in the disease pathogenesis as well as its progression. Neuroinflammation in PD leads to neurodegeneration, which is, in turn, regulated by the peripheral adaptive immunity, with CD4+ T cells being a significant player. Patients with PD have diverse CD4+ T cell phenotypes and functional profiles. These phenotypes vary, from being proinflammatory (Th1 and Th17) to anti-inflammatory (Th2 and Tregs). This report focuses on reviewing the expression of CD4+ T cells in PD and its role in the prognosis and treatment of PD.

A systematic review to identify novel clinical characteristics of monkeypox virus infection and therapeutic and preventive strategies to combat the virus.

Since May 2022, there has been a global increase in the number of Mpox virus (MPXV) cases in countries that were previously considered non-endemic. In July 2022, the World Health Organization (WHO) declared this outbreak a public health emergency of international concern. The objective of this systematic review is to examine the novel clinical features of Mpox and to assess the available treatment options for managing the disease in patients who are afflicted with it. We conducted a systematic search in several databases, including PubMed, Google Scholar, Cochrane Library, and the grey literature, from May 2022 to February 2023. We identified 21 eligible studies, which included 18,275 Mpox cases, for final qualitative analysis. The majority of cases were reported in men who have sex with men (MSM) and immunocompromised individuals with HIV (36.1%). The median incubation period was 7 days (IQR: 3-21). The novel clinical manifestations include severe skin lesions on the palms, oral and anogenital regions, as well as proctitis, penile edema, tonsillitis, ocular disease, myalgia, lethargy, and sore throat, without any preceding prodromal symptoms or systemic illness. In addition, fully asymptomatic cases were documented, and various complications, including encephalomyelitis and angina, were noted. Clinicians must be familiar with these novel clinical characteristics, as they can aid in testing and tracing such patients, as well as asymptomatic high-risk populations such as heterosexuals and MSM. In addition to supportive care, currently, there are several effective prophylactic and treatment strategies available to combat Mpox, including the vaccines ACAM2000 and MVA-BN7, as well as the immunoglobulin VIGIV and the antivirals tecovirimat, brincidofovir, and cidofovir against severe Mpox infection.

Fragment-Based Drug Discovery against Mycobacteria: The Success and Challenges.

The emergence of drug-resistant mycobacteria, including Mycobacterium tuberculosis (Mtb) and non-tuberculous mycobacteria (NTM), poses an increasing global threat that urgently demands the development of new potent anti-mycobacterial drugs. One of the approaches toward the identification of new drugs is fragment-based drug discovery (FBDD), which is the most ingenious among other drug discovery models, such as structure-based drug design (SBDD) and high-throughput screening. Specialized techniques, such as X-ray crystallography, nuclear magnetic resonance spectroscopy, and many others, are part of the drug discovery approach to combat the Mtb and NTM global menaces. Moreover, the primary drawbacks of traditional methods, such as the limited measurement of biomolecular toxicity and uncertain bioavailability evaluation, are successfully overcome by the FBDD approach. The current review focuses on the recognition of fragment-based drug discovery as a popular approach using virtual, computational, and biophysical methods to identify potent fragment molecules. FBDD focuses on designing optimal inhibitors against potential therapeutic targets of NTM and Mtb (PurC, ArgB, MmpL3, and TrmD). Additionally, we have elaborated on the challenges associated with the FBDD approach in the identification and development of novel compounds. Insights into the applications and overcoming the challenges of FBDD approaches will aid in the identification of potential therapeutic compounds to treat drug-sensitive and drug-resistant NTMs and Mtb infections.

Emerging tick-borne diseases and blood safety: summary of a public workshop.

Tick-borne agents of disease continue to emerge and subsequently expand their geographic distribution. The threat to blood safety by tick-borne agents is ever increasing and requires constant surveillance concomitant with implementation of appropriate intervention methods. In April 2017, the Food and Drug Administration organized a public workshop on emerging tick-borne pathogens (excluding Babesia microti and Lyme disease) designed to provide updates on the current understanding of emerging tick-borne diseases, thereby allowing for extended discussions to determine if decisions regarding mitigation strategies need to be made proactively. Subject matter experts and other stakeholders participated in this workshop to discuss issues of biology, epidemiology, and clinical burden of tick-borne agents, risk of transfusion-transmission, surveillance, and considerations for decision making in implementing safety interventions. Herein, we summarize the scientific presentations, panel discussions, and considerations going forward.

Constructing Item Banks for Measuring Quality of Life in Refractive Error.

SIGNIFICANCE: Existing patient-reported outcome instruments in refractive error are paper-based questionnaires. They are not comprehensive and psychometrically robust. This study has identified the content of the refractive error-specific item banks that aim to provide comprehensive and scientific measurement of refractive error-specific quality of life. PURPOSE: The purpose of this study was to identify minimally representative, optimally informative, and efficient sets of items for measuring quality of life in people with refractive error. METHODS: First, items were identified from existing patient-reported outcome instruments. Second, items were developed from qualitative studies with people with refractive error (48 and 101 in-depth interviews in Australia and Nepal, respectively). Third, classification and selection of items were done based on a set of systematic criteria using an iterative process of binning and winnowing. The resulting items underwent cognitive testing with people with refractive error in Australia and in Nepal. Each step was guided by an expert panel consensus. RESULTS: We retrieved 792 items from the existing patient-reported outcome instruments. From the interviews conducted in Australia, a total of 2367 comments were coded into 807 initial items. Similarly, from the interviews conducted in Nepal, 3477 comments were coded into 914 initial items. After binning and winnowing, followed by cognitive testing, a final set of items comprising 337 items for the Item-pool (Australia) and 308 items for the Item-pool (Nepal), both spanning 12 domains, was obtained. Forty-seven percent of items were common across the two item pools. In the Item-pool (Nepal), 65% items were common for corrected and uncorrected refractive error. CONCLUSIONS: We identified the content of two different sets of item banks to comprehensively measure the impact of refractive error on quality of life for people in Australia and Nepal, which may be applicable to high-income country settings and low- and middle-income country settings, respectively. Future work aims to develop computer-adaptive testing system to administer the item banks, resulting in useful measurement tools for researchers, clinicians, and policy planners.

Microbiological profile of corneal ulcer cases diagnosed in a tertiary care ophthalmological institute in Nepal.

BACKGROUND: Corneal ulcer, a major cause of monocular blindness in developing countries has consistently been listed as the major cause of blindness and visual disability in many of the developing nations in Asia, Africa and the Middle East, ranking second only to cataract. This study was carried out to determine the microbiological profile of corneal ulcer cases diagnosed among patients visiting Tilganga Institute of Ophthalmology (TIO), Nepal. METHODS: A total of 101 corneal scrapping samples were tested for routine culture and antibiotic susceptibility at the pathology department of TIO Nepal from April to October 2014. Microorganisms were identified by using standard microbiological procedures following the manual of American Society for Microbiology (ASM) and their antibiotic susceptibility test, performed by Kirby-Bauer disc diffusion method in conformity with the CLSI guideline. RESULTS: Out of 101 samples analyzed, 44.6% (45/101) showed positive growth with bacterial isolates i.e., 56% (25/45), more prevalent than fungus i.e., 44% (20/45). Among bacteria Streptococcus pneumoniae (31.1%, N = 14) was isolated in highest number whereas Fusarium (13.4%, N = 6) was the most common fungus species. Pseudomonas aeruginosa was the only Gram negative bacteria isolated from corneal ulcer cases. All bacterial isolates were found to be susceptible to the quinolone group of antibiotics (moxifloxacin followed by ofloxacin and ciprofloxacin). CONCLUSIONS: These findings showcase the current trend in the microbiological etiology of corneal ulcer in Nepal, which have important public health implications for the treatment as well as prevention of corneal ulceration in the developing world.

Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian infants: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Rotavirus is the most common cause of severe dehydrating gastroenteritis in developing countries. Safe, effective, and affordable rotavirus vaccines are needed in these countries. We aimed to assess the efficacy and tolerability of a monovalent human-bovine rotavirus vaccine for severe rotavirus gastroenteritis in low-resource urban and rural settings in India. METHODS: We did a randomised double-blind, placebo-controlled, multicentre trial at three sites in Delhi (urban), Pune (rural), and Vellore (urban and rural) between March 11, 2011, and Nov 5, 2012. Infants aged 6-7 weeks were randomly assigned (2:1), via a central interactive voice or web response system with a block size of 12, to receive either three doses of oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6-7 weeks, 10 weeks, and 14 weeks. Infants' families, study investigators, paediatricians in referral hospitals, laboratory staff, and committee members were all masked to treatment allocation. The primary outcome was incidence of severe rotavirus gastroenteritis (≥11 on the Vesikari scale). Efficacy outcomes and adverse events were ascertained through active surveillance. Analysis was by intention to treat and per protocol. The trial is registered with Clinical Trial Registry-India (CTRI/2010/091/000102) and ClinicalTrials.gov (NCT01305109). FINDINGS: 4532 infants were assigned to receive the 116E vaccine and 2267 to receive placebo, of whom 4354 (96%) and 2187 (96%) infants, respectively, were included in the primary per-protocol efficacy analysis. 71 events of severe rotavirus gastroenteritis were reported in 4752 person-years in infants in the vaccine group compared with 76 events in 2360 person-years in those in the placebo group; vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0-66·9; p=0·0013) and 56·4% (36·6-70·1; p<0·0001) in the first year of life. The number of infants needed to be immunised to prevent one severe rotavirus gastroenteritis episode was 55 (95% CI 37-97). The incidence of severe rotavirus gastroenteritis per 100 person-years was 1·5 in the vaccine group and 3·2 in the placebo group, with an incidence rate ratio of 0·46 (95% CI 0·33-0·65). Prevalence of immediate, solicited, and serious adverse events was similar in both groups. One case of urticaria in the vaccine group and one each of acute gastroenteritis and suspected sepsis in the placebo group were regarded as related to the study product. We recorded six cases of intussusception in the vaccine group and two in the placebo group, all of which happened after the third dose. 25 (<1%) infants in the vaccine group and 17 (<1%) in the placebo group died; no death was regarded as related to the study product. INTERPRETATION: Monovalent human-bovine (116E) rotavirus vaccine is effective and well tolerated in Indian infants. FUNDING: Department of Biotechnology and the Biotechnology Industry Research Assistance Council, Government of India; Bill & Melinda Gates Foundation to PATH, USA; Research Council of Norway; UK Department for International Development; National Institutes of Health, Bethesda, USA; and Bharat Biotech International, Hyderabad, India.

Prevalence of tuberculosis in Faridabad district, Haryana State, India.

BACKGROUND & OBJECTIVES: Epidemiological information on tuberculosis (TB) has always been vital for planning control strategies. It has now gained further importance for monitoring the impact of interventions to control the disease. The present study was done to estimate the prevalence of bacillary tuberculosis in the district of Faridabad in Haryana State of India among persons aged older than 15 years. METHODS: In this cross-sectional study, residents of Faridabad district were assessed for the prevalence of tuberculosis. Twelve rural and 24 urban clusters with estimated populations of 41,106 and 64,827 individuals were selected for the study. Two sputum samples were collected from individuals found eligible for inclusion. The samples were also cultured by modified Petroff's method and were examined for growth of Mycobacterium tuberculosis once a week for eight weeks. A person found positive by smear and/or culture was identified as sputum-positive pulmonary TB positive. RESULTS: A total of 105,202 subjects were enumerated in various clusters of the Faridabad district. There were 50,057 (47.58%) females and 55,145 (52.42%) males. Of these 98,599 (93.7%) were examined by the study group (47,976 females; 50,623 males). The overall prevalence of sputum smear or culture positive pulmonary tuberculosis in our study was found to be 101.4 per 100,000 population. INTERPRETATION & CONCLUSIONS: The present results showed that the prevalence of sputum positive pulmonary tuberculosis was higher in Faridabad district than the notification rates recorded by the World Health Organization for the contemporary period, a disparity that could be explained by a difference in case detection strategy employed for the study.

Factors associated with childhood ocular morbidity and blindness in three ecological regions of Nepal: Nepal pediatric ocular disease study.

BACKGROUND: Nepal Pediatric Ocular Diseases Study is a three year longitudinal population based study. Here we present the baseline survey report which aims to investigate various risk factors associated with childhood ocular morbidity and blindness in three ecological regions of Nepal. METHOD: This baseline survey is a population based cross sectional study. The investigation was conducted in a district from each of the following regions: Terai, Hill and Mountain. The Village Development Committees (VDCs) from each district were selected by random sampling. Three Community health workers were given training on vision screening and identification of abnormal ocular signs in children. They conducted a house to house survey in their respected districts examining the children and gathering a standardized set of data variables. Children with abnormal vision or ocular signs were then further examined by pediatric ophthalmologists. RESULTS: A total of 10950 children aged 0-10 years (5403 from Terai, 3204 from the hills, 2343 from the mountains) were enrolled in the study. However 681 (6.2%) were non responders. The male to female ratio was 1.03. The overall prevalence of ocular morbidity was 3.7% (95% CI of 3.4%-4%) and blindness was 0.07% (95% CI of 0.02%-0.12%). Ocular morbidity was more prevalent in the mountain region whereas blindness was more prevalent in the Terai region.Children from the Terai region were more likely to suffer from congenital ocular anomalies compared to the other regions. Children whose mother smoked, drank alcohol, or was illiterate were significantly afflicted with ocular diseases (p < 0.05). In addition,a higher prevalence of ocular disease was related to children with past medical history of systemic illnesses, abnormal postnatal period or missing childhood vaccinations. Blindness was more prevalent in children who suffered from a systemic illness. Females and under-nourished children were more likely to have ocular morbidity and blindness. CONCLUSION: It was found that childhood blindness was more prevalent in the Terai region, the undernourished, females and in those with co-morbid systemic illnesses. This study strongly suggests that prevention of childhood blindness requires additional resources to address these disparity.

Health literacy of common ocular diseases in Nepal.

BACKGROUND: Poor health literacy is often a key cause of lack of or delayed uptake of health care services. The aim of this study was to assess the health literacy of common ocular diseases, namely cataract, glaucoma, night blindness, trachoma and diabetic retinopathy in Nepal. METHODS: A cross sectional study of 1741 participants randomly selected from non-triaged attendants in the outpatient queue at Tilganga Institute of Ophthalmology, a semi urban general population of Bhaktapur district of Kathmandu Valley and patients attending rural outreach clinics. Participants responded to trained enumerators using verbally administered, semi structured questionnaires on their awareness and knowledge of cataract, glaucoma, diabetic retinopathy, night blindness, and trachoma. RESULTS: The awareness of cataract across the entire sample was 49.6%, night blindness was 48.3%, diabetic retinopathy was 29%, glaucoma was 21.3% and trachoma was 6.1%. Patients presenting to rural outreach clinics had poorer awareness of cataract, glaucoma, diabetic retinopathy, night blindness and trachoma compared to those from a semi-urban community and an urban eye hospital (p<0.05), Old age was directly associated with poorer awareness of cataract, glaucoma, night blindness, trachoma and diabetic retinopathy (p<0.05). Female gender was associated with lower awareness of cataract, glaucoma, night blindness and trachoma (p<0.05). Literacy was associated with greater awareness of cataract, glaucoma, diabetic retinopathy, night blindness and trachoma (p<0.05). Higher education was significantly associated with greater awareness of cataract, night blindness and trachoma (p<0.05). Multivariate analysis found that the awareness of common ocular diseases was significantly associated with level of education (p<0.05). Similarly, awareness of cataract, glaucoma, trachoma and night blindness was associated with female gender (p<0.05) whereas awareness of cataract, night blindness, trachoma and diabetic retinopathy was associated with age (p<0.05) but the awareness glaucoma and diabetic retinopathy was associated with camps. CONCLUSIONS: Low awareness of common ocular conditions is associated with factors such as female gender, old age, lower levels of education and rural habitation. A would be successful health promotion programs should specifically target health determinants to promote health literacy and to ensure timely utilization of eye care services.

Prevalence of health behaviors and their associated factors among a sample of university students in India.

OBJECTIVE: With advances in knowledge about health promotion, public health professionals are in search for the determinants of personal health behaviors. The purpose of this study was to assess the prevalence of health behaviors and its associated factors in a sample of Indian university students. MATERIALS AND METHODS: Using a cross-sectional survey, we assessed health behavior among a sample of randomly selected university students. The sample included 800 university students from non-health (mainly engineering and sciences) undergraduate courses of Gitam University, Visakhapatnam in India. The students were 541 (67.6%) males and 259 (32.4%) females in the age range of 17-20 years (Median age=18.2 years, SD=1.0). RESULTS: On average, students engaged in 15.8 out of 25 health behavior practices. There was a high rate of overweight and obesity (26.8% and 10.7%, respectively), low rate of brushing teeth at least twice a day (28.6%), annual dental check-up (25.8%), habitual seatbelt use (23%), and poor dietary patterns (79% ate less than the recommended fruit and vegetable consumption of five servings a day, and 68.5% did not avoid eating fat and cholesterol). In multivariate analysis among men, personal constraints (Odds Ratio=OR 1.75, Confidence Interval=CI 1.09-2.82), health benefits (OR=2.01, CI=1.27-3.17), and not suffering from depression (OR=0.60, CI=0.22-0.94) were associated with the health behavior index. Among women, those who were living away from their parents or guardians (OR=1.94, CI=1.06-3.55), economically better off (OR=2.16, CI=1.00-4.63), and had higher social support (OR=3.65, CI=1.75-7.63), were associated with the health behavior index. DISCUSSION: Students had a high proportion of health behavior practices. Several high health risk practices were identified, including overweight, poor dental practices, poor dietary and sleeping habits. It is hoped that the gender-specific predictors identified, including sociodemographics as well as social and mental health variables, can also be utilized in designing health promotion programs.

Association and Mechanisms of Proton Pump Inhibitors Use with Type-2 Diabetes Mellitus Incidence in Adults: A Systemic Review and Metaanalysis.

BACKGROUND: Proton pump inhibitors (PPIs) are an extensively prescribed class of anti-ulcer drugs. This systematic review aimed to investigate the association between PPI use and the risk of new-onset diabetes mellitus or type 2 diabetes (T2DM) incidence. METHODS: A comprehensive literature search was conducted in PubMed, Scopus, Cochrane Library, and ClinicalTrials.gov using the search terms "proton pump inhibitor," "proton pump inhibitors," "PPIs," "diabetes mellitus," and "type 2 diabetes" from inception to February 2023. Statistical analyses were performed using the "Review Manager 5.4" version, and a statistically highly significant P value <0.05 was set. RESULTS: This systematic review identified 12 studies (8 cohort, 1 RCT, and 3 case-control) with a total of 12, 64, 816 population, and the median age ranged from ≥18 yrs to ≤ 75 yrs. The pooled relative risk (RR) observations of a random-effects meta-analysis model showed that chronic exposure to PPI use has a significant association with T2DM risk incidence (RR, 2.44; 95% confidence interval, 1.31-4.54; I 2 = 99%, P < 0.00001). The systematic review findings of the three case-control studies also supported an association of dose-dependent and chronic use of PPIs with an incidence of T2DM among chronic users. CONCLUSION: The systematic review concludes that chronic PPI exposure increases the risk of T2DM incidence. The authors recommend the shortest possible duration of PPI use and not prescribing PPIs to high-risk prediabetics and those without a compelling indication for PPI use. Regular education to patients regarding adverse reactions with prolonged use may decrease the risk of adverse effects associated with PPIs. The authors suggest that gut dysbiosis, hypergastrinemia, hypomagnesemia, decreased pancreatic secretions and IGF-1 levels, and PXR activation associated with chronic acid suppression among chronic PPI users and the potency of PPIs might explain the association between abnormal glucose metabolism and T2DM incidence. Finally, the authors recommend further randomized controlled trials to investigate the association between PPIs and the risk of new-onset T2DM incidence.

Grossing to reporting of Wilms tumor with emphasis on proper sampling in treatment-naive and postchemotherapy specimens and their clinicopathological correlation with outcome.

Context: Emphasis on grossing to reporting for the assessment of histopathological parameters predicting outcomes in Wilms tumor. Aims: To analyze various clinicopathological parameters that effect outcomes in treatment naïve and post chemotherapy Wilms tumor specimens. Settings and Design: This was a retrospective observational study. Subjects and Methods: All patients diagnosed with Wilms tumor between 2012 and 2018 at our institute will be included with their clinical findings, laboratory reports, and radiological findings. The patients will be categorized into two groups based on treatment protocol (Society of Pediatric Oncology (SIOP) or the National Wilms Tumor Study Group/Children's Oncology Group (COG) guidelines) used. Details of Grossing and reporting protocols used for the in pre treatment and post treatment specimens will be analyzed. Follow-up till December 2020 will be analyzed. Statistical Analysis Used: Chi-square and Fisher's exact tests were used for statistical analysis. Results: A total of 36 patients with the diagnosis of Wilms tumor were included in the present study. The mean age of presentation was 3.9 ± 0.7 years, and males were more common than females. Most of them presented as abdominal mass and few with isolated hematuria. Twenty-six (72%) patients were treated under SIOP protocol with preoperative neoadjuvant chemotherapy. Ten patients underwent upfront surgery as per COG protocol. In SIOP group patients, the mean tumor size was 9.3cm. Forty percent (n = 10) we mixed histological type followed by blastemal type constituting (32%, n = 8). Regressive and epithelial histological types constituted 16% (n = 4) and 12% (n = 3), respectively. In the SIOP group 72% (n = 19) had no anaplasia and 28% (n = 7) had anaplasia. Fifty seven percent (n = 15) cases were Stage I, followed by 26.9% n = 7) and 11.5% (n = 3) being Stage II and Stage III, respectively. Ten patients underwent upfront surgery as per COG protocol. The mean tumor size among this group was 8 cm ranging from 7 cm to 11 cm. Eight (80%) cases had favorable histology and two cases showed focal anaplasia. Heterologous differentiation is seen in 3 (70%). Out of the 10 cases, one case was Stage I, six were Stage 2, one was Stage III, and two were clinical Stage IV. None of the cases showed either vessel or lymph node metastasis. All the patients received adjuvant chemotherapy postsurgery and were followed up till December 2020 for (at least 3 years). Of 25 patients in the SIOP group, 18 (72%) had complete remission with no radiological evidence of residual disease. Of the 10 patients in the COG group, 6 (70%) had complete remission. Conclusions: Histopathological evaluation of Wilms tumor is a critical aspect in the management of Wilms tumor, as tumor characteristics are different in the tumors treated under SIOP and COG protocols, which will ultimately affect the prognostic risk stratification. This necessitates the knowledge of the important grossing and reporting of these tumors under the two protocols.

Efficacy and safety of thrice weekly DOTS in tuberculosis patients with and without HIV co-infection: an observational study.

BACKGROUND: Despite the latest World Health Organization guidelines advocating daily therapy in HIV-TB co-infected individuals, there are few recent studies comparing outcomes of thrice-weekly anti-tuberculosis treatment in HIV-positive and HIV-negative patients with TB. The present study sets out to compare TB treatment outcomes in these two groups in the Indian national programme, which currently involves thrice-weekly therapy for all, regardless of HIV status. METHODS: HIV-positive and HIV-negative were consecutively screened for enrolment into this prospective observational study, carried out at the All India Institute of Medical Sciences hospital, New Delhi, India, between 2006 and 2010. Patients were given short-course thrice-weekly rifampicin-based therapy, with all HIV-positive patients being started on highly active antiretroviral therapy at least 14 days after commencing TB treatment. Patients were regularly followed-up for 24 months after completion of treatment. RESULTS: 150 HIV-positive, 155 HIV-negative patients were enrolled consecutively for the study. Significantly higher treatment success (93.5% vs. 76.7% at end of treatment, p < 0.001) and lower mortality (2.8% vs. 21.6% on follow up, p < 0.001) were observed in HIV-negative patients. No significant difference was found in treatment failure (p = 0.16), sputum smear (p = 0.58) and culture conversion (p = 0.55), and non-serious adverse event incidence (p = 0.851) between the two groups. Low baseline CD4 cell count (<100 cells/ mm3) was the only predictor of mortality in HIV-TB patients (odds ratio 8 · 43, p = 0 · 013). CONCLUSIONS: Thrice-weekly anti-tuberculosis therapy is more effective in HIV-negative than in HIV-positive patients. However, outcomes in this HIV co-infected cohort were found to be similar to those reported previously with daily therapy, with no safety concerns. This should prompt further study into whether intermittent or daily therapy should be used universally in resource-poor settings, using large well executed randomised controlled trials. TRIAL REGISTRATION: NCT No. 00698334.

Burden of healthcare utilization and out-of-pocket costs among individuals with NCDs in an Indian setting.

Non communicable diseases (NCDs) are now the major cause of death and disability worldwide. It increasingly affects people from developing as well as developed countries. Over the coming decades the burden from NCDs is projected to rise particularly fast in the developing world. There is a lack of optimal data collection about the burden of risk factors related to NCDs especially in the developing countries. To assess the burden of healthcare utilization and out-of-pocket costs associated with NCDs in an Indian setting. A cross sectional study was performed to enroll a convenient sample of 166 participants aged 18 years and above from a tertiary hospital in Punjab, a Northern state of India. The data was gathered during the period of Feb 2010-April 2010. A mixed methods approach was used to assess the burden of diabetes, hypertension, high cholesterol, and their associated risk factors. Further we evaluated the burden of healthcare utilization and out-of-pocket costs associated with these conditions using self-reported assessments. Results showed the average age of the participants was 50 years, 63 % (n = 104) were females, 32 % (n = 53) had education less than high school and 20 % (n = 33) had no formal education. About 96 % of the study participants were living with a partner. Majority of the study participants were non-smokers and 17 % (n = 27) of them reported to have history of alcohol consumption. The majority of the participants had access to cell phones (94 %; n = 156) and about 40 % (n = 66) had computers at home. About 33 % (n = 55) of the study participants had some form of previous knowledge of computers. Majority of the study participants went to the private hospital (47.5 %) for seeking healthcare. About 32 % (n = 53) also sought healthcare from some kind of healthcare professional including a primary care doctor or a nurse or even a pharmacist in a village setting. Doctor visits related to diabetes were higher as compared to the individuals either with hypertension or high cholesterol. However; the out-of-pocket costs of the visit to the healthcare professional were much higher for hypertension than for diabetes or high cholesterol. A strengthened surveillance system, effective inter-sectoral action, and improved access to basic healthcare are pivotal to prevent NCDs. A multifaceted NCDs surveillance system could help us measure the burden of risk factors, its associated health care utilization and out of pocket costs, and further facilitate interventions that can guide evidence based decision making.

Comparative evaluation of estrus synchronization protocols on reproductive performance and estrus behavior in Barbados Black Belly sheep.

Background and Aim: Estrus synchronization of ewes has been accomplished using several protocols with various degrees of success in improving reproductive efficiency and obtaining the most effective protocol used in sheep farming. This study aimed to compare the effectiveness of three treatment protocols and to record the intensity and duration of estrus signs and pregnancy rate in Barbados Black Belly (BBB) sheep. Materials and Methods: Thirty-two primipara BBB ewes aged 18-24 months were equally divided into three treatment groups. T1: the ewes were injected intramuscularly with 2 mL Lutalyse (PGF2α) (10 mg) on days 0 and 10. T2: 1 mL Fertiline (50 µg; Gonadorelin acetate) on day 0 and 2 mL lutalyse (10 mg) on day 7. T3: 1 mL fertiline (50 µg) on day 0, 2 mL lutalyse (10 mg) on day 7, and 1 mL Fertiline (50 µg) on day 9. Estrus response was assessed using naturally mating rams and ewes. Pregnancy was determined using ultrasonography between 55 and 80 days after the last hormonal injection. The following estrus signs were noted: Swollen vulva, mucus discharge, sniffing, excitement, loss of appetite, mounting, and rapid tail movement. Results: Of the expressed signs, swollen vulva was most frequent, whereas loss of appetite and mucus discharge were the least overt signs recorded. The estrus response (%), onset (%), and duration (h) in ewe synchronization of the three treatment protocols were 100%, 58.3 ± 23.4%, and 48.0 ± 18.2 h (T1), 100%, 61.7 ± 41.2%, and 45.0 ± 27.0 h (T2), and 37.5%, 32.1 ± 1.7%, and 29.2 ± 1.25 h (T3), respectively. The pregnancy rates were 87.5%, 87.5%, 37.5%, and 50.0% in T1, T2, T3, and T4, respectively. Conclusion: Prostaglandin F2α+PGF2α and GnRH+PGF2α synchronization protocols were more effective in the fertilization of BBB ewes with better expression of estrus signs compared with the GnRH+PGF2α+GnRH (OVS) protocol.

Current Prospects in Rheumatoid Arthritis: Pathophysiology, Genetics, and Treatments.

BACKGROUND: An autoimmune inflammatory disease, rheumatoid arthritis (RA), predominantly affects the synovium joint lining, augmenting disability, early mortality, and socioeconomic difficulty. Therefore, current updates on pharmacological therapies are crucial for developing drugs to treat the disease at each stage. OBJECTIVE: This review attempts to compile a thorough analysis of current developments in our knowledge of RA pathogenesis and disease-modifying drugs, with the aim of providing insights for next-generation RA therapeutics. RESULTS: According to the literature, the most successful drugs for treatment techniques described so far in this include (cs) DMARDs (sub-class of DMARDs), tsDMARDS (targeted synthetic DMARDS), and bDMARDs (biological DMARDs). However, current pharmacologic therapy (consisting of biological, conventional, and creative views of small molecule anti-rheumatic drugs that treat the disease or DMARD) remains the cornerstone of rheumatoid arthritis treatment with which significant progress toward disease remission has been accomplished. CONCLUSION: The pathobiology of RA involves cytokine messengers such as B and T-cells, and an intricate interplay of pro-inflammatory cytokines responsible for activating and developing effector cells, in turn, accountable for local disease and systemic symptoms. Despite the fact that the cause of rheumatoid arthritis is not known, new treatments have been created as a result of better approaches towards the biology of the disease. As they target molecules directly implicated in the genesis of rheumatoid arthritis, these drugs may be more effective, targeted, and less harmful in the short and long term than standard therapies.