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Human papillomavirus (HPV) testing of self-collected vaginal samples has potential to improve coverage of cervical screening programmes, but current guidelines mostly require those HPV positive on a self-sample to attend for routine screening. A pragmatic modified stepped-wedge implementation feasibility trial was conducted at primary care practices in England. Individuals aged 25 to 64 years who were at least 6 months overdue for cervical screening could provide a self-collected sample. The primary outcomes included the monthly proportion of non-attenders screened, changes in coverage, and uptake within 90 days. Self-samples from 7,739 individuals were analysed using Roche Cobas 4800. Individuals with a positive self-sample were encouraged to attend clinical screening. In this post hoc study of the trial, we related the HPV type (HPV16, HPV18, or other high-risk type) and cycle threshold (Ct) value on the self-sample to the results of clinician-collected sample and cervical intraepithelial neoplasia grade 2 or worse (CIN2+). We wished to triage HPV-positive individuals to immediate colposcopy, clinician sampling, or 12-month recall depending on risk. A total of 1,001 women tested positive through self-samples, and 855 women who had both an HPV-positive self-sample and a subsequent clinician-sample were included in this study. Of these, 71 (8.3%) had CIN2+. Self-sample Ct values were highly predictive of HPV in the clinician sample. Combining HPV type and Ct value allowed stratification into 3 risk groups; 44/855 (5%) were high-risk of whom 43% (19/44, 95% confidence interval [29.7%, 57.8%]) had CIN2+. The majority (52.9%, 452/855) were low-risk, of whom 4% (18/452, 95% CI [2.5%, 6.2%]) had CIN2+. The main limitation of our study was the colposcopy assessment was restricted to individuals who had abnormal cytology after positive results of both self-sample and clinician-collected sample. HPV type and Ct value on HPV-positive self-samples may be used for triage. The difference in the risk of CIN2+ in these groups appears sufficient to justify differential clinical management. A prospective study employing such triage to evaluate laboratory workflow, acceptability, and follow-up procedure and to optimise clinical performance seems warranted. ISRCTN12759467.

Objective: Although cyclophosphamide (CP), an alkylating agent, is used in the treatment of cancer owing to its broad-spectrum efficacy, its metabolites exhibit severe undesired toxicities in normal cells. The present study was aimed to investigate the chemoprotective potential of Coccinia indica against CP-induced oxidative stress, genotoxicity, and hepatotoxicity. Materials and Methods: Rodents were orally pre-treated with Coccinia indica extract (200, 400, and 600 mg/kg) for five consecutive days. On 5th day, these animals were injected with CP (50 mg/kg i.p) and sacrificed after 24 hrs. for the evaluation of oxidative stress, hepatotoxicity, micronucleus formation, and chromosomal aberrations. Results: We found that the CP significantly increased malondialdehyde (MDA) and decreased catalase and glutathione (GSH) levels in brain, and it was significantly reversed by Coccinia indica extract (400 and 600 mg/kg). Further, pre-treatment with Coccinia indica extract (200, 400, 600 mg/kg) significantly and dose-dependently reduced micronuclei formation and incidence of aberrant cells. We also found that the CP-induced increase in the serum biomarker enzymes like alkaline phosphatase (ALP), alkaline aminotransferase (ALT), and aspartate aminotransferase (AST) were significantly reduced by Coccinia indica extract. Conclusion: Thus, the present results indicate the protective effect of Coccinia indica extract against CP-induced oxidative stress, genotoxicity, as well as hepatotoxicity.

A comprehensive review of the authors’ research focused on the development of novel and efficient synthetic strategies for structurally diverse heterocyclic scaffolds is presented. Among these, the thiazolidinone scaffold has emerged as highly versatile and pharmaceutically significant framework in modern medicinal chemistry, owing to its broad clinical relevance. The review covers the recent literature on the design and synthesis of diverse 1,3-thiazolidin-4-one derivatives and investigation of their biological properties and highlights the tremendous potential of thiazolidinones in advancing organic and medicinal chemistry.

Cefpodoxime proxetil (CP) solubility in binary solvent mixtures (1,4-dioxane + water and acetonitrile + water) was tested using the gravimetric method at temperature between 298.15 to 318.15 K and under normal atmospheric pressure. The experimental mole fraction solubility of CP was increased with increasing temperature as well as with the proportion of co-solvent in all systems. Then Apelblat, Buchowski-Ksiazczak, Van’t Hoff, and the modified Jouyban-Acree models were used for the prediction of the theoretical mole fraction solubility of CP. The experimental and theoretical mole fraction solubility were found to be good in this arrangement. Additionally, thermodynamics modeling of CP was carried out by using Van’t Hoff’s equation. The data on the solubility and thermodynamics would be useful in the production, isolation, separation, and crystallization of CP.

Context: Rheumatic heart disease (RHD) predominantly affects adults. However, in developing countries like India, it is the most common acquired heart disease in children. The prevalence of RHD also varies from the region to region in the same country due to the differences in educational, economic, and social status as well as health-care facilities of the region. Aim: The aim of the study is to establish and discuss the spectrum of RHD in children from Western India and to explore the relationship between severity of valvular lesion by the age and sex of the children with RHD. Methods: Echocardiographic findings of children (N = 820) ≤18 years with RHD seen at our institute from January 2018 to December 2018 were retrospectively analyzed. RHD was screened by echocardiography. All the echocardiogram were analyzed for the pattern and severity of various valve lesions and associated abnormalities. Results: Eight hundred and twenty children had a diagnosis of RHD. Maximum patients [476 (57.1%)] were from the age group of 13-18 years without any gender difference (418 male and 402 female). Mitral regurgitation (MR) was the most common lesion found in 81.46% children. Aortic regurgitation (AR) was seen in 29.76%, mitral stenosis (MS) was found in 20.48%, tricuspid regurgitation was seen in 66.83%, and aortic stenosis (AS) was found in 0.73% children. AR was found more common in males as compared to females (P = 0.0004). Majority of patients (69.5%) had single mitral valve involvement. Four hundred and eight patients (49.8%) had severe MR, 122 patients (14.9%) had severe MS, 62 patients (7.6%) had severe aortic regurgitation, and 2 (0.2%) patients had severe AS at the time of first presentation. Pulmonary hypertension was found in 69% of children. Children with MS and AS were older than those without MS and AS (P = 0.0001). Conclusion: Majority of children had severe valvular lesion and pulmonary hypertension at the time of first presentation. RHD is the leading cause of heart failure in children with requirement of surgical/catheter intervention and long-term medical management.