Green synthesis and biological evaluation of novel 5-fluorouracil derivatives as potent anticancer agents

This study reports the formation of 5-FU co-crystals with four different pharmacologically safe co-formers; Urea, Thiourea, Acetanilide and Aspirin using methanol as a solvent. Two fabrication schemes were followed i.e., solid-state grinding protocol, in which API and co-formers were mixed through vigorous grinding while in the other method separate solutions of both the components were made and mixed together. The adopted approaches offer easy fabrication protocols, no temperature maintenance requirements, no need of expensive solvents, hardly available apparatus, isolation and purification of the desired products. In addition, there is no byproducts formation, In fact, a phenomenon embracing the requirements of green synthesis. Through FTIR analysis; for API the NH absorption frequency was recorded at 3409.02 cm^?1 and that of CO was observed at 1647.77 cm^?1. These characteristics peaks of 5-FU were significantly shifted and recorded at 3499.40 cm^?1 and 1649.62 cm^?1 for 5-FU-Ac (3B) and 3496.39 cm^?1 and 1659.30 cm^?1 for 5-FU-As (4B) co-crystals for NH and CO groups respectively. The structural differences between API and co-crystals were further confirmed through PXRD analysis. The characteristic peak of 5-FU at 2θ = 28.79918^o was significantly shifted in the graphs of co-crystals not only in position but also with respect to intensity and FWHM values. In addition, new peaks were also recorded in all the spectra of co-formers confirming the structural differences between API and co-formers. In addition, percent growth inhibition was also observed by all the co-crystals through MTT assay against HCT 116 colorectal cell lines in vitro. At four different concentrations; 25, 50, 100 and 200 µg/mL, slightly different trends of the effectiveness of API and co-crystals were observed. However; among all the co-crystal forms, 5-FU-thiourea co-crystals obtained through solution method (2B) proved to be the most effective growth inhibitor at all the four above mentioned concentrations.     

Information and communication technology in cardiovascular disease prevention in developing countries: hype and hope. Report of the International Collaboration on Information Use in Cardiovascular Health Promotion in Developing Countries

Information can be an important tool in promoting a prevention strategy to address the emerging epidemic of cardiovascular disease in developing countries. Advances in information and communication technology offer new promises for global access to information and for global mobilization to prevent and control cardiovascular disease. This is especially true for health professionals, whose needs in areas such as networking, exchange of expertise and access to relevant advances remain unfulfilled. Information technology can also sensitize the lay public to the magnitude of cardiovascular diseases, creating awareness about risk states, and highlighting preventive strategies. Effective application mandates that the technology be relevant to local needs. Cost, feasibility, and relevance of information need to be considered before wide adoption is advocated. Several initiatives, such as ProCOR, Global Cardiovascular Infobase, Heartfile, and the Virtual Congress of Cardiology, have successfully utilized information technology to promote cardiovascular prevention. The experience of these initiatives suggests that, while information technology holds great potential, there are many potential perils, such as the widening global information gap, inequitable access, and irrelevant information. For now, information technology must be viewed as part of a broader strategy, which includes conventional communication media, to address the unmet information needs for cardiovascular prevention globally. Enlightened policies can exploit the energies of the recent information boom for promoting cardiovascular prevention, taking into account the considered limitations.     

Immune-related therapeutics: an update on antiviral drugs and vaccines to tackle the COVID-19 pandemic

The coronavirus disease 2019 (COVID-19) pandemic rapidly spread globally. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, is a positive-sense single-stranded RNA virus with a reported fatality rate ranging from 1% to 7%, and people with immune-compromised conditions, children, and older adults are particularly vulnerable. Respiratory failure and cytokine storm-induced multiple organ failure are the major causes of death. This article highlights the innate and adaptive immune mechanisms of host cells activated in response to SARS-CoV-2 infection and possible therapeutic approaches against COVID-19. Some potential drugs proven to be effective for other viral diseases are under clinical trials now for use against COVID-19. Examples include inhibitors of RNA-dependent RNA polymerase (remdesivir, favipiravir, ribavirin), viral protein synthesis (ivermectin, lopinavir/ritonavir), and fusion of the viral membrane with host cells (chloroquine, hydroxychloroquine, nitazoxanide, and umifenovir). This article also presents the intellectual groundwork for the ongoing development of vaccines in preclinical and clinical trials, explaining potential candidates (live attenuated-whole virus vaccines, inactivated vaccines, subunit vaccines, DNA-based vaccines, protein-based vaccines, nanoparticle-based vaccines, virus-like particles and mRNA-based vaccines). Designing and developing an effective vaccine (both prophylactic and therapeutic) would be a long-term solution and the most effective way to eliminate the COVID-19 pandemic.     

A twin study exploring the association between childhood emotional and behaviour problems and specific psychotic experiences in a community sample of adolescents

Background

Childhood emotional and behaviour problems are antecedents for later psychopathology. This study investigated genetic and environmental influences shaping the longitudinal association between childhood emotional and behaviour problems and specific PEs.

Method

In a community‐based twin sample, parents reported on emotional and behaviour problems when twins were ages 7 and 12 years. At age 16 years, specific PEs were measured using self‐reports and parent reports. Structural equation model‐fitting was conducted.

Results

Childhood emotional and behaviour problems were significantly associated with paranoia, cognitive disorganisation and parent‐rated negative symptoms in adolescence (mean r = .15–.38), and to a lesser extent with hallucinations, grandiosity and anhedonia (mean r = .04‐.12). Genetic influences on childhood emotional and behaviour problems explained significant proportions of variance in adolescent paranoia (4%), cognitive disorganisation (8%) and parent‐rated negative symptoms (3%). Unique environmental influences on childhood emotional and behaviour problems explained ≤1% of variance in PEs. Common environmental influences were only relevant for the relationship between childhood emotional and behaviour problems and parent‐rated negative symptoms (explaining 28% of variance) and are partly due to correlated rater effects.

Conclusions

Childhood emotional and behaviour problems are significantly, if weakly, associated with adolescent PEs. These associations are driven in part by common genetic influences underlying both emotional and behaviour problems and PEs. However, psychotic experiences in adolescence are largely influenced by genetic and environmental factors that are independent of general childhood emotional and behaviour problems, suggesting they are not merely an extension of childhood emotional and behaviour problems.     

A Shared Genetic Propensity Underlies Experiences of Bullying Victimization in Late Childhood and Self-Rated Paranoid Thinking in Adolescence

Background: Bullying is a risk factor for developing psychotic experiences (PEs). Whether bullying is associated with particular PEs, and the extent to which genes and environments influence the association, are unknown. This study investigated which specific PEs in adolescence are associated with earlier bullying victimization and the genetic and environmental contributions underlying their association. Method: Participants were 4826 twin pairs from a longitudinal community-based twin study in England and Wales who reported on their bullying victimization at the age of 12 years. Measures of specific PEs (self-rated Paranoia, Hallucinations, Cognitive disorganization, Grandiosity, Anhedonia, and parent-rated Negative Symptoms) were recorded at age of 16 years. Results: Childhood bullying victimization was most strongly associated with Paranoia in adolescence (r = .26; P < .01), with weaker associations with Hallucinations, Cognitive Disorganization, parent-rated Negative Symptoms (r = .12–.20; P < .01), Grandiosity (r = .04; P < .05), and Anhedonia (r = .00, n.s.). Bivariate twin model-fitting demonstrated that bullying victimization and Paranoia were both heritable (35% and 52%, respectively) with unique environmental influences (39% and 48%, respectively), and bullying victimization showed common environmental influences (26%). The association between bullying victimization and Paranoia operated almost entirely via genetic influences (bivariate heritability = 93%), with considerable genetic overlap (genetic correlation = .55). Conclusion: In contrast to the assumed role of bullying victimization as an environmental trigger, these data suggest that bullying victimization in late childhood is particularly linked to self-rated Paranoia in adolescence via a shared genetic propensity. Clinically, individuals with a history of bullying victimization are predicted to be particularly susceptible to paranoid symptoms.Key words: bullying victimization, psychotic experiences, twin study, paranoia     

Status of Methane Emission from Indian Wetlands (Saline vs. Freshwater): A Mini Review

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Wetlands are amongst the most important natural ecosystems on earth. India is blessed to have several...     

Smoking and inflammatory bowel disease: trends in familial and sporadic cohorts

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) result from genetic and environmental factors. Never smoking and formerly smoking increase the risk of UC, whereas smoking exacerbates the course of CD. We sought to define the age-dependent effects of smoking on the development of UC and CD in familial and sporadic cohorts. METHODS: University of Chicago patients diagnosed with UC or CD between 1990 and 2002 were surveyed about their tobacco use relative to their diagnosis. Smoking trends were used to estimate age-dependent odds ratios and the attributable risks of smoking in the IBD cohort compared to in the general population. RESULTS: One thousands and thirteen patients were included in the study: 245 with sporadic UC; 216 with sporadic CD; 249 with familial UC; and 303 with familial CD. Being an ex-smoker conferred an increased risk for UC in the 25-44 age group in both the sporadic and familial cohorts, but not in the 45-64 age group in the familial UC cohort. Furthermore, there was no difference in tobacco use between patients with sporadic CD and the general population, although there was a significant increase in smoking in younger patients with familial CD. CONCLUSIONS: Ex-smokers make up an increasing percentage of older patients diagnosed with UC, accounting for more than 35% of the attributable risk of late onset (>45 years) UC and a large component of the second peak in diagnosis. Current smokers account for a large percentage of patients diagnosed at a younger age with familial CD but not with sporadic CD. Families with IBD should be counseled that early tobacco use significantly increases the risk of developing CD or, if an ex-smoker, UC at a young age.