Immunogenicity of SARS-CoV-2 vaccines BBV152 (COVAXIN®) and ChAdOx1 nCoV-19 (COVISHIELD™) in seronegative and seropositive individuals in India: a multicentre, nonrandomised observational study.

Background: There are limited global data on head-to-head comparisons of vaccine platforms assessing both humoral and cellular immune responses, stratified by pre-vaccination serostatus. The COVID-19 vaccination drive for the Indian population in the age group 18-45 years began in April 2021 when seropositivity rates in the general population were rising due to the delta wave of COVID-19 pandemic during April-May 2021. Methods: Between June 30, 2021, and Jan 28, 2022, we enrolled 691 participants in the age group 18-45 years across four clinical sites in India. In this non-randomised and laboratory blinded study, participants received either two doses of Covaxin® (4 weeks apart) or two doses of Covishield™ (12 weeks apart) as per the national vaccination policy. The primary outcome was the seroconversion rate and the geometric mean titre (GMT) of antibodies against the SARS-CoV-2 spike and nucleocapsid proteins post two doses. The secondary outcome was the frequency of cellular immune responses pre- and post-vaccination. Findings: When compared to pre-vaccination baseline, both vaccines elicited statistically significant seroconversion and binding antibody levels in both seronegative and seropositive individuals. In the per-protocol cohort, Covishield™ elicited higher antibody responses than Covaxin® as measured by seroconversion rate (98.3% vs 74.4%, p < 0.0001 in seronegative individuals; 91.7% vs 66.9%, p < 0.0001 in seropositive individuals) as well as by anti-spike antibody levels against the ancestral strain (GMT 1272.1 vs 75.4 binding antibody units/ml [BAU/ml], p < 0.0001 in seronegative individuals; 2089.07 vs 585.7 BAU/ml, p < 0.0001 in seropositive individuals). As participants at all clinical sites were not recruited at the same time, site-specific immunogenicity was impacted by the timing of vaccination relative to the delta and omicron waves. Surrogate neutralising antibody responses against variants-of-concern including delta and omicron was higher in Covishield™ recipients than in Covaxin® recipients; and in seropositive than in seronegative individuals after both vaccination and asymptomatic infection (omicron variant). T cell responses are reported from only one of the four site cohorts where the vaccination schedule preceded the omicron wave. In seronegative individuals, Covishield™ elicited both CD4+ and CD8+ spike-specific cytokine-producing T cells whereas Covaxin® elicited mainly CD4+ spike-specific T cells. Neither vaccine showed significant post-vaccination expansion of spike-specific T cells in seropositive individuals. Interpretation: Covishield™ elicited immune responses of higher magnitude and breadth than Covaxin® in both seronegative individuals and seropositive individuals, across cohorts representing the pre-vaccination immune history of most of the vaccinated Indian population. Funding: Corporate social responsibility (CSR) funding from Hindustan Unilever Limited (HUL) and Unilever India Pvt. Ltd. (UIPL).

Sacral agenesis without maternal diabetes: a case report.

Introduction: Sacral agenesis is a rare congenital condition that is characterized by sacrococcygeal bone agenesis. It is associated with spinal cord anomalies as well as problems with the genitourinary system, large bowel, and lower extremities. Fetal ultrasound allows for diagnosis even before birth. Case presentation: The authors present the case of a 1-year-old girl with sacral agenesis type III and bilateral congenital talipes equinovarus with spina bifida who was born to a nondiabetic mother and had a normal anomaly scan. Clinical discussion: People with less severe forms of sacral agenesis can live a normal life, and it is not connected with cognitive impairment; however, concomitant bladder, colon, and lower limb disorders cause considerable morbidity. The majority of treatment is supportive, frequently requiring orthopedic, urological, gastroenterological, pediatric, and physiotherapy support. Conclusion: Genetic and prepregnancy counseling, as well as early screening of high-risk mothers, remain the only options for prevention of the disease since treatment is mostly supportive.

Nurses' knowledge and attitudes regarding children's pain assessment and management in Nepal.

Pain is frequently experienced by children in hospital, and international guidelines for appropriate pain assessment and management are available. Optimal management of paediatric pain has important long-term health, psychosocial, and economic benefits. However, evidence indicates that globally there are deficits in nurses' understanding of paediatric pain assessment and management. This study explored knowledge and attitudes regarding paediatric pain assessment and management among nurses at a tertiary children's hospital in Nepal. In this cross-sectional study all 140 nurses at a tertiary children's hospital in Nepal, were invited to complete the validated Paediatric Nurses Knowledge and Attitudes Survey. Findings revealed substantial deficits in nurse's knowledge and erroneous attitudes towards pain assessment and management in children. Test scores ranged from 14% to 56%, with mean scores of 38%, with no nurses achieving a recommended pass score of 80% regarding knowledge and attitudes in paediatric pain management. Consistent with previous research, nurses had insufficient knowledge and attitudes that did not reflect best practice regarding pain assessment and management in children. Education programmes targeting both trainees and registered nurses are essential to enable nurses to deliver evidence-based care and improve outcomes for children and their families.

A rare case of left-sided obturator hernia diagnosed by computed tomography.

Obturator hernia is a rare condition that is difficult to detect clinically. We highlight the importance of a CT scan in establishing an early diagnosis of an obturator hernia, effective surgical intervention planning, thereby enhancing the result.

Diagnostics and Therapeutic Potential of miR-205 and miR-34a in Ovarian Cancer Management: A miRNA-Target-Based Analysis.

Epithelial ovarian cancer (EOC) treatment strategies mainly focused on surgery combined with chemotherapy. Recent targeted therapy techniques emerge as milestone and could be used for management of ovarian cancer (OC) progression with more efficacy. The aim is to evaluate the therapeutic and diagnostic potential of microRNA (miRNA) in management of EOC using in silico and quantitative real-time PCR (qRT-PCR) expression analysis. We performed functional enrichment and miRNA-Target genes expression analysis in 48 EOC and 22 normal tissue samples using qRT-PCR and correlated with miRNA expression data in matched samples to evaluate the diagnostic and therapeutic potential of miRNA in OC management. In silico functional enrichment analysis revealed miRNA association with disease. Target genes of miRNAs participate in several biologically important pathways leading to cancer progression. Targets of miRNA-205 and miRNA-34a were significantly downregulated, and upregulated, respectively, in EOC. Moreover, significant negative correlation between relative expression of miRNA-205 and target genes (BCL2, ZEB1, E2F1, and TP53) was observed with r = -0.813; r = -0.755; r = -0.559; and r = -0.767, respectively. Similarly, miRNA-34a also showed higher negative correlation with target genes (MDM4, MAPK3, BRCA1, AREG) with r = -0.840; r = -0.870; r = -0.622; and r = -0.623, respectively. In addition, receiver operating characteristics analysis of combined miRNA panel, miRNA-205-Target gene panel, and miRNA-34a-Target gene panel exhibited higher diagnostics value with area under the curve (AUC) of 92.7 (p < 0.0001), 94.8 (p < 0.0001), and 98.3 (p < 0.0001), respectively. Negative Correlation between miRNA and target genes expression data in matched samples highlights therapeutic potential of miRNA in EOC management. Moreover, combined diagnostic potential of miRNA-target gene panel could predict risk of EOC with higher AUC, sensitivity, and specificity.

Poisoning among Autopsies Conducted in the Department of Forensic Medicine and Toxicology in a Tertiary Care Centre.

Introduction: Poisoning is a serious public health issue in developing countries like Nepal. Information about poisoning may be helpful for poisoning prevention and hospital treatment, aiding in the development of measures that lower the morbidity and mortality associated with poisoning. This study aimed to find out the prevalence of poisoning among autopsies conducted in the Department of Forensic Medicine and Toxicology in a tertiary care centre. Methods: A descriptive cross-sectional study was conducted among autopsied cases in the Department of Forensic Medicine and Toxicology in a tertiary care centre. Data from 1 October 2020 to 1 April 2022 was collected between 22 December 2022 to 30 December 2022 from records after receiving ethical approval from the Institutional Review Committee. All autopsied cases during the study period were included with the exclusion of decomposed bodies. Convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. Results: Among 399 autopsies, 63 (15.79%) (12.21-19.37, 95% Confidence Interval) were found to be cases of poisoning. Among 63 cases, 35 (55.56%) were male and 28 (44.44%) were female. The most common substance causing poisoning was unknown with 31 (49.21%) cases, followed by organophosphates with 24 (38.10%) cases and rodenticide with 8 (12.70%) cases. Conclusions: The prevalence of poisoning among autopsies was found to be higher than similar studies conducted in similar settings. Keywords: autopsy; organophosphate poisoning; poisoning; suicide.

Depression and Anxiety among Patients with Type II Diabetes Mellitus in Chitwan Medical College Teaching Hospital, Nepal.

The prevalence of depression and anxiety disorders is common among people with diabetes mellitus. Coexistence of diabetes and depression/anxiety increases the risk of diabetes complications and reduces the overall quality of life. Hence, this study aimed to assess the depression and anxiety among patients with type 2 diabetes mellitus in Chitwan. Descriptive survey was carried out among 296 purposively selected clinically diagnosed type 2 diabetes patients admitted in the Chitwan Medical College Teaching Hospital from 15th June 2018 to 17th September 2019. Patients were interviewed using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorders-7 (GAD-7). Data were analyzed using descriptive and inferential statistics. Of 296 diabetic patients, 48.6% were 60 years and above, 59.5% female and 61.5% literate; their common occupation was agriculture (38.2%) followed by household work (26.4%). Nearly two-thirds (62.8%) of diabetes patients had other chronic comorbid conditions. Depression and anxiety were observed among 57.8% and 49.7% of diabetes patients, respectively. While observing the severity, 27.4%, 19.6%, 8.4%, and 2.4% of patients had mild, moderate, moderately severe, and severe depression, respectively. Likewise, 24.7%, 20.3%, and 4.7% of patients had mild, moderate, and severe anxiety, respectively. Current living status, educational status, medicine adherence, satisfaction toward current treatment, and history of mental illness in the family were found to be significant factors associated with the anxiety of patients with diabetes. Further, educational status, smoking habit, satisfaction towards current treatment, and history of diabetes in family were the factors associated with depression. Prevalence of depression and anxiety is high among admitted patients with diabetes mellitus, and many factors are associated with it. Hence, regular screening services are essential along with diabetes management plan for timely identification and treatment of the vulnerable groups in the healthcare centers.

Psychiatric Morbidities in Patients with Non-communicable Diseases among Inpatients of Medicine Department in a Tertiary Care Hospital: A Descriptive Cross-sectional Study.

INTRODUCTION: Psychiatric morbidities are common among patients with chronic non-communicable diseases. These diseases have high morbidity, mortality, and higher health costs. However, psychiatric conditions are often underdiagnosed and undertreated in our country. This study aimed to find out the psychiatric morbidities among patients with non-communicable diseases admitted in inpatients units of the medicine department. METHODS: A descriptive cross-sectional study was conducted in the inpatients of the medicine department of a tertiary care hospital among 926 patients with chronic non-communicable diseases. Ethical approval was obtained from the Chitwan Medical College Institutional Review Committee (Ref.No.IRC:2074/75:38). A convenient sampling technique was used. Patients were interviewed using the Patients Health Questionnaire. Data analysis was performed using Statistical Package for Social Sciences version 16. RESULTS: Among 926 non-communicable disease patients, psychiatric morbidities observed were somatization 612 (66.1%) anxiety 319 (34.4%), and depression 379 (40.9%). Patients with multiple non-communicable diseases had higher psychiatric morbidities compared to patients with a single disease. CONCLUSIONS: Psychiatric morbidities are common among admitted patients suffering from non-communicable diseases in Nepal. Hence, regular screening services are needed in all levels of health care centers to identify and treat the risk groups on time.

Menstrual and Gonadal Function Alterations in Women with Systemic Lupus Erythematosus.

PURPOSE: Systemic lupus erythematosus (SLE) is an autoimmune disorder and may affect the reproductive health status of the women. Objective is to analyze the types, incidence of various menstrual disturbances in these women, to identify risk factors and to assess the gonadal function. METHODS: The prospective cohort study was conducted in the SLE clinic of the Rheumatology Department of IPGMEandR, Kolkata from April 2010 to April 2011. Out of 152 females attending clinic, 110 patients fulfilling criteria were included in the study. RESULTS: Mean age of the study population was 27.25±3.4 years. Sixty six cases had menstrual abnormalities (12.72% amenorrhea, 44.45% oligomenorrhea, 2.7% premature ovarian failure, 10.9% menorrhogia). When comparative analysis of demographic, hormonal, ovarian Doppler and therapeutic variables of normal and abnormal cycles was carried out, following parameters were significantly more related to patients with abnormal cycle ; SLEDAI score (12.48±5.53 vs 8.69±4.9; p=0.00), disease duration (6.46±3.08 vs 4.3±1.36; p< 0.05), TSH (7.73±8.64 vs 3.07±2.06; p=0.00.), LH (6.55±4.38 vs 4.56±3.29; p=0.02), a high normal prolactin (12.57±7.75 vs 8.73±3.07; p=0.02), peak systolic velocity (6.53±2.17 vs 9.12±2.1; p=0.00), end-diastolic volume (4.21±2.9 vs 9.35±2.32; p=0.00) and cumulative dose of steroid (24.02±41.44 vs 9.32±9.96; p=0.01).Cyclophosphamide with cumulative dose ≥10 gm was related to amenorrhea and affected gonadal function. Gonadal insufficiency was evident in 33.63% and 2.72% had ovarian failure. CONCLUSIONS: Reduced menstruation is a major health concern in women with SLE as it is frequent and can result in depressed and failed gonadal function later. Doppler study of ovaries is a novel way of depiction of gonadal status in these women. Certain risk factors and revolving treatment part can be preventable.

Very stable electron field emission from strontium titanate coated carbon nanotube matrices with low emission thresholds.

Novel PMMA-STO-CNT matrices were created by opened-tip vertically aligned multiwalled carbon nanotubes (VA-MWCNTs) with conformal coatings of strontium titanate (STO) and poly(methyl methacrylate) (PMMA). Emission threshold of 0.8 V/µm was demonstrated, about 5-fold lower than that of the as-grown VA-MWCNTs. This was obtained after considering the related band structures under the perspective of work functions and tunneling width as a function of the STO thickness. We showed that there is an optimum thickness of STO coatings to effectively reduce the work function of CNTs and yet minimize the tunneling width for electron emissions. Furthermore, simulation and modeling suggest that PMMA-STO-CNT matrices have suppressed screening effects and Coulombs' repulsion forces between electrons in adjacent CNTs, leading to low emission threshold, high emission density, and prolonged emission stability. These findings are important for practical application of VA-MWCNTs in field emission devices, X-ray generation, and wave amplification.

Ultrahigh sensitivity assays for human cardiac troponin I using TiO2 nanotube arrays.

Rapid, highly sensitive troponin assays for the analysis of serum at the point-of-care are particularly desirable for the effective treatment of myocardial infarction (MYI). TiO(2) nanotube arrays constitute a low cost, high surface area, semiconducting architecture with great promise for biosensing applications due to their compatibility with multiple detection techniques. Using TiO(2) nanotube arrays functionalized with highly robust and ordered carboxyalkylphosphonic acid self-assembled monolayers, we have developed a simple and highly sensitive fluorescence immunoassay which can detect concentrations of human cardiac troponin I as low as 0.1 pg ml(-1) without the use of enzymatic amplification. Varying the morphological parameters of the nanotube arrays allows tuning the detection range over 6 orders of magnitude of the troponin concentration from 0.1 pg ml(-1)-100 ng ml(-1).

1,4-Dioxane and ergosterol derivatives from Withania somnifera roots.

The chemical investigation on the n-hexane extract of Withania somnifera roots has yielded octacosane, oleic and stearic fatty acids, stigmasterone, stigmasterol, sitostanone, oleanolic acid along with the ergosterol and 1,4-dioxane derivatives as new compounds. The isolation of alkenyl-1,4-dioxane compound is rare, whereas the ergosterol derivative may have biogenetic significance in the lactone formation in the E ring of withanolides. The presence of a 1,4-dioxane derivative in the nonpolar extract of roots assumes importance as this type of compound has not been reported earlier from W. somnifera. The structures of new compounds were elucidated by spectroscopic methods and chemical transformations.

Ferric reducing, antiradical and beta-carotene bleaching activities of nicotinic acid and picolinic acid bioconjugates of curcumin.

Although curcumin displays several beneficial properties, its medicinal use is limited by its low bioavailability. In the present study we report the antioxidant potentials of two bioconjugates of curcumin with nicotinic acid and picolinic acid: di-O-nicotinoyl curcumin [1,7-bis (4-O nicotinoyl-3-methoxyphenyl)-1,6-heptadiene-3, 5-dione] and di-O-picolinoyl curcumin [1,7-bis (4-O-picolinoyl-3-methoxyphenyl)-1,6-heptadiene-3, 5-dione], in terms of ferric reducing, radical scavenging and beta-carotene bleaching abilities, and comparing the observed activity with that of curcumin. Results demonstrate that both the bioconjugates possess higher antioxidant potentials as evidenced by enhanced ferric reducing, radical scavenging and beta-carotene bleaching abilities, in comparison with curcumin. On the basis of our results we conclude that these bioconjugates of curcumin may be better than curcumin for medicinal and pharmacological applications.

Stable electron field emission from PMMA-CNT matrices.

We have created PMMA-CNT matrices by embedding opened-tip vertically aligned multiwalled carbon nanotubes (VA-MWCNTs) with poly(methyl methacrylate) (PMMA). These PMMA-CNT matrices are excellent electron field emitters with an emission threshold field of 1.675 V/µm, more than 2-fold lower that that of the as-grown sample. In addition, the emission site density from these matrices is high, merely filling up the entire sample surface. Emission stability test at ∼1.35 mA/cm(2) was performed continuously for 40 h with no significant degradation. On the basis of our theoretical simulation and hypothetical modeling, we attribute these performances to the reduced screening effect and fewer Joule heatings due to the shorter effective transport distance of the electrons in MWCNTs.

Withanolides from Withania somnifera roots.

Two new and seven known withanolides along with beta-sitosterol, stigmasterol, beta-sitosterol glucoside, stigmasterol glucoside, alpha+beta glucose were isolated from the roots of Withania somnifera. Among the known compounds, Viscosa lactone B, stigmasterol, stigmasterol glucoside and alpha+beta glucose are being reported from the roots of W. somnifera for the first time. One of the new compounds contained the rare 16beta-acetoxy-17(20)-ene the other contained unusual 6alpha-hydroxy-5,7alpha-epoxy functional groups in the withasteroid skeleton. The structures were elucidated by spectroscopic methods and chemical transformations.