Essential medicines for cardiovascular diseases in India: Rapid appraisal of policies and processes at the subnational level

BACKGROUND The burden of cardiovascular diseases (CVDs) and response to health systems vary widely at the subnational level in India. Our study aimed to assess the variation in state-level access to medicines for CVDs by comparing the essential medicines lists (EMLs) at the national and subnational levels in India and by rapid appraisal of the existing policies and processes of drug procurement. METHODS We assessed the inclusion of six classes of medicines for CVDs in the recent and publicly available national and subnational EMLs from July to September 2018 in the states of Telangana and Madhya Pradesh. We examined the drug procurement and distribution policies and processes using documentary review and five key informant interviews between March and June 2018. RESULTS The WHO’s EML, India’s national EML, and 21 of 28 publicly available (75%) Indian state and Union Territory EMLs included all six classes of essential medicines for CVDs. However, some medicines were not included in the policy packages of essential medicines meant for primary health centres. Both the states used centralized tendering and decentralized distribution as part of the public sector drug procurement process. The requirement was based on the previous year’s consumption. The approximate time between procurement planning and distribution was 7–8 months in both the states. CONCLUSION Substantial variation exists in the selection of drugs for CVDs in EMLs at the subnational level in India. Improving forecasting techniques for requirement of medicines and reducing time lags between forecasting and distribution to health facilities may allow for better access to essential medicines.

Comparative Effectiveness of Herbal and Conventional Toothpaste on Prevention of Dental Caries: Systematic Review and Meta-Analysis

Dental caries is a global oral health problem caused due to localized demineralization of the enamel. Chemical plaque control is used as an adjuvant to mechanical plaque control in removing biofilm, thereby preventing dental caries. In recent times, there has been a renewed interest in nature?based products. This systematic review aimed to analyse the existing literature to compare the effectiveness of herbal and conventional dentifrices on prevention of dental caries. A search was done in the databases of PubMed and Google Scholar in July 2020 for the related topic. A hand search was done from the references of primary studies and other clinical trial registry sites. Randomized control trials, comparative clinical trials, and in vitro studies in which the effectiveness of herbal and conventional dentifrices on prevention of dental caries were included after review by the reviewers. The systematic search revealed a total of thirty?two publications from which ten publications were included. Five studies were clinical studies and five were in vitro studies. All the studies used microbiological analysis for the determination of cariogenic microorganisms in plaque and saliva, whereas one study used pH of plaque and saliva. Among the included studies, all studies had a high risk of bias with level 2 evidence. With the evidence available, it can be concluded that herbal dentifrices and fluoride dentifrices have similar antimicrobial activity against cariogenic microorganisms.

Association of family history of cardiometabolic diseases (CMDs) and individual health behaviours: Analysis of CARRS study from South Asia

Objectives: Family history is considered as an important predictor of cardiovascular diseases (CVDs) and diabetes. Available research findings suggest that family history of chronic diseases is associated with perceived risk of disease and adoption of healthy behaviours. We examined the association between family history of cardio-metabolic diseases (CMDs) and healthy behaviours among adults without selfreported CMDs. Methods: Cross-sectional data of 12,484 adults, without self-reported CMDs, from the baseline survey of Centre for cArdiometabolic Risk Reduction in South-Asia (CARRS) cohort study were analysed. Results: Family history was positively associated with non-smoking and high fruits & vegetables consumption in the age group of 45e64 years and moderate to high physical activity in the age group _x0001_65 years after adjusting for sex, education, wealth index, city and body mass index. Conclusions: Understanding perceived risks and cultural or psychological factors related to family history through ethnographic studies may deepen understanding of these associations.

Evaluation of the efficacy of plaque reduction and gingival health among 6-12 years old school children before and after a short term daily intake of probiotic lozenge - A comparative study

Context: Probiotics are defined as live microorganisms which when delivered in adequate amounts provides health benefit in the host. Dietary supplements like lozenge seem to be the easy and acceptable vehicle for ingestion of probiotics in young children. Aim: To assess the efficacy of probiotics in plaque reduction and gingival health among 6?12 years school children before and after short term daily intake of Probiotic lozenge. Settings and Design: This Comparative study was conducted among 60 children in the age group 6–12 years. Thirty children in experimental group; who were given lozenge containing probiotic bacteria twice daily, one in the morning and another in the evening after brushing for one month. The placebo lozenge group also followed the same protocol. Statistical Analysis Used: SPSS version 21. Results: The Probiotic lozenge group was found to have statistically significant reduction in plaque scores when compared to that of the placebo group with P < 0.001 and there was also a significant improvement in gingival health. Conclusion: An effective reduction in plaque accumulation and gingival inflammation was found with the use of probiotic lozenges and hence proved the therapeutic value of the same.

Primer of Epidemiology IV. Study designs II: Interventional or experimental designs

In this article, we describe experimental study designs and focus on randomized controlled trials. Experimental studies are intervention studies in which the investigator tests a new treatment on a selected group of patients. In a controlled design, the effects of an intervention (new treatment) are measured by comparing the outcome in the experimental group with that in a control group. Experimental studies are similar to cohort studies except that the exposure is a deliberate change (intervention) made by the researcher in one group of participants and it overcomes confounding because the treatment is assigned randomly. Further, we discuss various types of randomization (random sequence allocation) and importance of allocation concealment and blinding for proper assessment of outcomes in randomized trials.

Rapid burst of ethylene evolution by premature seed: A warning sign for the onset of spongy tissue disorder in Alphonso mango fruit?

Moisture stress induced in premature seeds due to the breakdown of funiculus in Alphonso mango led to the burst ofethylene evolution, which in turn caused a sudden increase of polyphenol oxidase activity in the pulp, resulting in thedevelopment of a black spot near the seed base. Reduced levels of very long chain fatty acids in 70% mature seeds withblack spots were associated with a sudden increase of cytokinins followed by a rapid rise of starch-metabolizing enzymesculminating in the onset of pre-germination events. Concurrently, an overproduction of p-OH benzoic acid inhibitedamylase and polygalacturonase enzymes and led to partial degradation of the stored starch and pectin in the pulp. A paralleldrop in climacteric ethylene production by the pulp led to incomplete ripening coupled with changes in composition, textureand aroma of the pulp, characteristic of spongy tissue. The results have provided strong experimental evidence to supportthe fact that increased competition for resources among developing fruits for the synthesis of seed fat plays a critical role inspongy tissue formation in Alphonso mango. The major highlight of the study is that rapid ethylene evolution by prematureseed is an early warning sign for the initiation of spongy tissue formation in Alphonso mango.

Efficacy of a mouthwash containing essential oils and curcumin as an adjunct to nonsurgical periodontal therapy among rheumatoid arthritis patients with chronic periodontitis: A randomized controlled trial

Purpose: The purpose of this study was to assess the efficacy of mouthwash containing essential oils and curcumin (MEC) as an adjunct to nonsurgical periodontal therapy on the disease activity of rheumatoid arthritis (RA) among RA patients with chronic periodontitis (CP). Materials and Methods: A triple-blinded controlled trial was conducted among 45 female RA patients with CP randomized into three treatment groups as follows: Group A: scaling and root planing (SRP) with 0.2% chlorhexidine mouthwash as an adjunct (n = 15), Group B: SRP with MEC as an adjunct (n = 15), and Group C: SRP alone (n = 15). RA disease activity was assessed using erythrocyte sedimentation rate, serum C-reactive protein, serum anti-citrullinated protein antibody, and serum rheumatoid factor. Periodontal disease activity was assessed using plaque index, clinical attachment level (CAL), and pocket depth (PD). All parameters were recorded at baseline and 6 weeks thereafter. Data were assessed using one-way ANOVA and paired t-test. Results: A significant reduction in periodontal and RA disease activity parameters was observed from baseline to 6 weeks following intervention (P < 0.05). The highest percentage of mean reduction in plaque index and RA parameters from baseline to 6 weeks was observed in Group B followed by Groups A and C. The highest percentage of mean reduction in PD and CAL was observed in Group A followed by Groups B and C (P < 0.001). Conclusion: This study reveals that MEC as an adjunct to SRP is effective in reducing the disease activity of RA and CP, thereby warranting the use of the same.

Clinical and pathologic factors predicting reclassification in active surveillance cohorts

ABSTRACT The incidence of small, lower risk well-differentiated prostate cancer is increasing and almost half of the patients with this diagnosis are candidates for initial conservative management in an attempt to avoid overtreatment and morbidity associated with surgery or radiation. A proportion of patients labeled as low risk, candidates for Active Surveillance (AS), harbor aggressive disease and would benefit from definitive treatment. The focus of this review is to identify clinicopathologic features that may help identify these less optimal AS candidates. A systematic Medline/PubMed Review was performed in January 2017 according to PRISMA guidelines; 83 articles were selected for full text review according to their relevance and after applying limits described. For patients meeting AS criteria including Gleason Score 6, several factors can assist in predicting those patients that are at higher risk for reclassification including higher PSA density, bilateral cancer, African American race, small prostate volume and low testosterone. Nomograms combining these features improve risk stratification. Clinical and pathologic features provide a significant amount of information for risk stratification (>70%) for patients considering active surveillance. Higher risk patient subgroups can benefit from further evaluation or consideration of treatment. Recommendations will continue to evolve as data from longer term AS cohorts matures.

Differential expression of carotenoid biosynthetic pathway genes in two contrasting tomato genotypes for lycopene content.

Tomato (Solanum lycopersicum L.) is one of the model plant to study carotenoid biosynthesis. In the present study, the fruit carotenoid content were quantified at different developmental stages for two contrasting genotypes, viz. IIHR- 249-1 and IIHR-2866 by UPLC. Lycopene content was high in IIHR-249-1 (19.45 mg/100 g fresh weight) compared to IIHR-2866 (1.88 mg/100 g fresh weight) at the ripe stage. qPCR was performed for genes that are involved in the carotenoid biosynthetic pathway to study the difference in lycopene content in fruits of both the genotypes. The expression of Phytoene synthase (PSY) increased by 36-fold and Phytoene desaturase (PDS) increased by 14-fold from immature green stage to ripe stage in IIHR-249-1. The expression of Chloroplast lycopene β-cyclase (LCY-B) and Chromoplast lycopene β cyclase (CYC-B) decreased gradually from the initial stage to the ripe stage in IIHR-249- 1. IIHR 249-1 showed 3- and 1.8-fold decrease in gene expression for Chloroplast lycopene β-cyclase (LCY-B) and Chromoplast lycopene β-cyclase (CYC-B) .The F2 hybrids derived from IIHR-249-1 and IIHR-2866 were analysed at the ripe stage for lycopene content. The gene expression of Chloroplast lycopene β-cyclase (LCY-B) and Chromoplast lycopene β-cyclase (CYC-B) in high and low lycopene lines from F2 progenies also showed the decrease in transcript levels of both the genes in high lycopene F2 lines. We wish to suggest that the differential expression of lycopene β- cyclases can be used in marker-assisted breeding.

Do seed VLCFAs trigger spongy tissue formation in Alphonso mango by inducing germination.

Spongy tissue is a physiological disorder in Alphonso mango caused by the inception of germination-associated events during fruit maturation on the tree, rendering the fruit inedible. Inter-fruit competition during active fruit growth is a major contributing factor for the disorder which leads to reduced fat content in spongy tissue affected fruits. This study was, therefore, carried out to determine the possible association between seed fats and ST formation. The study of the fat content during fruit growth showed that it increased gradually from 40% fruit maturity. At 70% maturity, however, there was a sudden increase of fat content of whole fruit, leading to acute competition and resulting in differential allocation of resources among developing fruits. As a result, the seed in spongy-tissue-affected mature ripe fruit showed a marked drop in the levels of fats and the two very long chain fatty acids (VLCFAs), tetracosanoic acid and hexacosanoic acid together with an increase of linolenic acid and a fall in oleic acid contents, which are known to be key determinants for the initiation of pre-germination events in seed. Subsequently, a rise in the level of cytokinin and gibberellins in ST seed associated with a fall in abscisic acid level clearly signalled the onset of germination. Concurrently, a significant reduction in the ratio of linolenic acid/linoleic acid in pulp led to the loss of membrane integrity, cell death and the eventual formation of spongy tissue. Based on the above, it is concluded that a significant reduction in the biosynthesis of VLCFAs in seeds during fruit growth might trigger pre-germination events followed by a cascade of biochemical changes in the pulp, leading to lipid peroxidation and membrane injury in pulp culminating in ST development. Thus, this study presents crucial experimental evidence to highlight the critical role played by VLCFAs in inducing ST formation in Alphonso mango during the pre-harvest phase of fruit growth.

case series of two cases of juxta-adrenal schwannoma presenting as adrenal mass lesion and review of the literature

Schwannomas are rare tumors in the retroperitoneal location. They can pose a diagnostic dilemma when presenting as an adrenal mass lesion due to their imaging characteristics. We report two cases of juxta-adrenal schwannomas presenting as symptomatic adrenal mass lesions. In both the cases, the clinical examination and functional evaluation was unremarkable and the radiological examination revealed a mixed intense adrenal mass lesion in one case with predominantly hyperintense areas and a very hyperintense lesion in another, in T2-weighted images, mimicking a adrenocortical malignancy and a pheochromocytoma respectively. Both cases were treated by surgical excision. Histopathological examination established the correct diagnosis of schwannoma, which was confirmed by immunohistochemical staining. Juxta-adrenal schwannoma is rare tumors of the retroperitoneum, which should also be borne in mind whenever encountering large nonsecreting adrenal tumors. We report a unique imaging characteristic, which helps in preoperative identification these rare lesions

Zooplankton diversity of Chikkadevarayana canal in relation to physico-chemical characteristics.

Plankton diversity and physico-chemical parameters are an important criterion for evaluating the suitability of water for irrigation and drinking purposes. In this study, we tried to assess zooplankton species richness, diversity and evenness to predict the state of Chickadevarayana canal water of Cauvery River according to physico-chemical parameters. A total of 51 taxa were recorded with 22 rotifers, 5 copepods, 6 cladocerans, 1 ostracoda and 17protozoans. More number of zooplankton species were recorded in Darasaguppe (30) followed by Edmuri (26), Kennala (20), Pandavpura (19) and Gendehosahalli (16). Among the rotifers, Euchlanis sp. species was abundant (194). Acantholeberis curvirostris was predominant among cladocerans (970). Among copepods, numerical superiorities were found in the case Cyclops sp. Cypris sp. was recorded in the ostracoda. Centropyxis aculeate repeated abundance in protozoans (412). The water samples analyzed for temperature, pH, electrical conductivity, alkalinity, hardness, dissolved oxygen, phosphate, sulphate and nitrate did not indicate variation. The occurrence of Asplanchna herricki, Lacrymaria sp, Brachionus pala and Monostyla lunaris showed highest similarity of occurrence reaching above 90%. The study revealed that the presence of certain species like Monostyla, Lepadella, Leydigia, Keratella, Branchionus and Cypris species can be considered as a biological indicator for eutrophication.

Polygalacturonase inhibitor protein from fruits of anthracnose resistant and susceptible varieties of Chilli (Capsicum annuum L).

Chilli fruit is highly susceptible to anthracnose infection at the stage of harvest maturity, due to which the fruit yield in the leading commercial variety Byadgi is severely affected. Field studies on screening of several varieties for resistance to anthracnose have shown that a variety of chilli AR-4/99K is resistant to anthracnose infection. In many crops, resistance to fungal attack has been correlated with PGIP activity in developing fruits based on which transgenic varieties have been developed with resistance to fungi. The present study was carried out to determine whether anthracnose resistance in AR-4/99K was due to the increased levels of PGIP alone and/ or due to differences, if any, in the properties of PGIP. Hence, a comparative study of the properties of polygalacturonase inhibitor protein (PGIP) isolated from fruits of anthracnose resistant chilli var AR-4/99K and a susceptible variety Byadgi was conducted with the objective of utilizing the information in genetic transformation studies. Both the PGIPs from anthracnose resistant and susceptible varieties of chilli exhibited similarities in the elution pattern on Sephadex gel, DEAE cellulose, PAGE and SDS-PAGE. The two PGIPs were active over a wide range of pH and temperature. Both PGIPs showed differential inhibitory activity against polygalacturonase (PG) secreted by Colletotrichum gleosporoides, C. capsici, C. lindemuthianum, Fusarium moniliforme and Sclerotium rolfsii. The inhibitory activity of PGIP from both resistant and susceptible varieties was the highest (82% and 76%, respectively) against the PG from Colletotrichum capsici, a pathogen causing anthracnose rot of chilli, while the activity was lower (1.27 to 12.3%) on the other fungal PGs. Although PGIP activity decreased with fruit maturation in both the varieties, the resistant variety maintained a higher activity at 45 days after flowering (DAF) as compared to the susceptible variety which helped it to overcome the infection by anthracnose as against the susceptible variety (Byadgi) in which PGIP activity was drastically reduced at maturity. The molecular mass of PGIP as determined by SDS-PAGE was found to be 37 kDa. N-terminal sequence analysis of the PGIP showed the first six amino acid residues from N-terminal end were Asp-Thr-His-Lys-Ser-Glu (DTHKSE), respectively. The similarities in properties of the two PGIPs support the earlier findings that resistance of AR-4/99K to anthracnose fungus is a result of its higher PGIP activity at maturity.

Expression of the Japanese encephalitis virus NS3 and NS2b proteins as glutathione S-transferase fusions.

Flaviviruses generate their structural and nonstructural proteins by proteolytic processing of a single large polyprotein precursor. These proteolytic events are brought about both by host cell signalase and a virally encoded protease. The virally encoded proteolytic activity has been shown to reside within the nonstructural protein 3 (NS3) and requires the product of the nonstructural 2b (NS2b) gene. In order to obtain sufficient quantities of pure NS2b and NS3 proteins for kinetic analysis, we have expressed both these proteins in recombinant systems as fusions to glutathione S-transferase (GST). The fusion constructs were driven by the strong bacteriophage T7 promoter. Transfection of these constructs into the African green monkey kidney cell line CV-1 previously infected with a recombinant vaccinia virus expressing the T7 RNA polymerase resulted in synthesis of the fusion proteins. Both the fusion proteins could be purified to homogeneity in a single step using a glutathione agarose affinity matrix.

Advanced sub social behaviour in the scorpion Heterometrus fulvipes Brunner (Arachnida).

Scorpions arc generally non-social, solitary animals that interact with conspecifics at birth, courtship or predation only· The present study reports the presence of advanced sub social behaviour in Heterometrus fulvipes Brunner and evaluates the importance of its burrowing as a cause for such social behaviour· Heterometrus fulvipes constructed deep angular burrows at the base of plants· Burrows provided (i) protection against predation, (ii) increased availability of food and (iii) ideal microclimate for year round activity of the scorpions· No cannibalism was observed in laboratory maintained colonies· The risk of predation and the difficult by immatures to dig tunnels during dry soil conditions may have forced the mother and offspring to live together in the burrow for longer durations. The cohabitation of relative offsprings transforms the burrow into a nest· The members of a colony exhibits division of labour for nest expansion and in foraging· The mother communicates with the immatures through "Buzz" sound and may provide premasticated food· There is food sharing also among colony members· All these behaviours indicate the presence of advanced sub social behaviour in Heterometrus fulvipes·