Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major problems for treatment of gallbladder carcinoma. The dramatic associations of this orphan cancer with various genetic and environmental factors are responsible for its poorly defined pathogenesis. An understanding to the relationship between epidemiology, molecular genetics and pathogenesis of gallbladder cancer can add new insights to its undetermined pathophysiology. Present review article provides a recent update regarding epidemiology, pathogenesis, and molecular genetics of gallbladder cancer. We systematically reviewed published literature on gallbladder cancer from online search engine PubMed (http://www.ncbi.nlm.nih.gov/pubmed). Various keywords used for retrieval of articles were Gallbladder, cancer Epidemiology, molecular genetics and bullion operators like AND, OR, NOT. Cross references were manually searched from various online search engines (http://www.ncbi.nlm.nih.gov/pubmed,https://scholar.google.co.in/, http://www.medline.com/home.jsp). Most of the articles published from 1982 to 2015 in peer reviewed journals have been included in this review.

This was a crossover study comparing a mucin-based artificial saliva (Saliva Orthana) and pilocarpine hydrochloride (Salagen) in the management of xerostomia in patients with advanced cancer. The pilocarpine was found to be more effective than the artificial saliva in terms of mean change in visual analogue scale scores for xerostomia (P = 0.003). Furthermore, more patients reported that it had helped their xerostomia, and more patients wanted to continue with it after the study. However, the pilocarpine was found to be associated with more side-effects than the artificial saliva (P < 0.001). These side-effects were usually reported as being mild. Of the patients who used both treatments, 50% preferred the artificial saliva, and 50% preferred the pilocarpine. The commonest reason for preferring the artificial saliva was the fact that it was a spray, rather than a tablet.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed more than 4 million humans globally, but there is no bona fide Food and Drug Administration–approved drug-like molecule to impede the COVID-19 pandemic. The sluggish pace of traditional therapeutic discovery is poorly suited to producing targeted treatments against rapidly evolving viruses. Here, we used an affinity-based screen of 4 billion DNA-encoded molecules en masse to identify a potent class of virus-specific inhibitors of the SARS-CoV-2 main protease (Mpro) without extensive and time-consuming medicinal chemistry. CDD-1714, the initial three-building-block screening hit (molecular weight [MW] = 542.5 g/mol), was a potent inhibitor (inhibition constant [Ki] = 20 nM). CDD-1713, a smaller two-building-block analog (MW = 353.3 g/mol) of CDD-1714, is a reversible covalent inhibitor of Mpro (Ki = 45 nM) that binds in the protease pocket, has specificity over human proteases, and shows in vitro efficacy in a SARS-CoV-2 infectivity model. Subsequently, key regions of CDD-1713 that were necessary for inhibitory activity were identified and a potent (Ki = 37 nM), smaller (MW = 323.4 g/mol), and metabolically more stable analog (CDD-1976) was generated. Thus, screening of DNA-encoded chemical libraries can accelerate the discovery of efficacious drug-like inhibitors of emerging viral disease targets.

Background: Recognizing the potential of the country's large youth population and the importance of protecting and supporting its health and well-being, the Government of India committed to strengthening its programmes and systems for adolescents, initially through the Adolescent Reproductive and Sexual Health Strategy (ARSH) launched in 2005 and, subsequently, through the National Adolescent Health Programme (Rashtriya Kishore Swaasthya Karyakram or RKSK) launched in 2014. In 2016, in response to a request from the Government of India, the World Health Organisation undertook a rapid programme review of ARSH and RKSK at the national level and in four states (Haryana, Madhya Pradesh, Maharashtra and Uttarakhand) to identify and document lessons learnt in relation to four domains of the programmes (governance, implementation, monitoring and linkages) that could be used to enhance current and future adolescent health programming in India. Methodology and findings: A rapid programme review methodology was utilised to gain an overview of the successes and challenges of the two adolescent health programmes. A desk review of policy statements, Program Implementation Plans (PIPs) (Program Implementation Plan (PIP) is an annual process of planning, approval and allocation of budgets of various programmes under the National Health Mission (NHM). It is also used for monitoring of physical and financial progress made against the approved activities and budget.), reports and data provided by the four State governments was conducted alongside 70 semi-structured interviews with health, education and NGO officials at national, state, district and block levels. Data showed that the ARSH Strategy put adolescent health on the agenda for the first time in India, though insufficient human and financial resources were mobilised to ensure maximum impact. Further, the Strategy's focus on clinical service provision in a limited number of health facilities with a complementary focus on promoting community support and adolescent demand for them meant that services were not as easily accessible to adolescents in their communities, and in addition many were not even aware of them. Under RKSK, significant investment has been made in adequate management structures, as well as in community engagement and clinical service delivery at all levels of the health system. Monitoring the quality of service delivery remains a challenge in all four of the states, as does training of counsellors, nodal officers and other implementing partners. Additionally, further thought and action are required to ensure that peer educators are properly trained, supported and retained for the programme. Conclusions: India's RKSK clearly integrated learning from the earlier ARSH Strategy. The findings of this review present an opportunity for the government and its partners to ensure that future investment in adolescent health programming continues to be framed around lessons learnt across India.

Gallbladder cancer (GBC) is the most frequent biliary tract malignancy. Wide variations in GBC incidence and familial and epidemiological data suggest involvement of a genetic component in its etiopathogenesis. A systematic review of genetic association studies in GBC was performed by applying a meta-analysis approach and systematically reviewing PubMed database using appropriate terms. Odds ratios (ORs) and 95% confidence intervals (CIs) were appropriately derived for each gene–disease association using fixed and random effect models. Meta-regression with population size and genotyping method was also performed. Study quality was assessed using a 10-point scoring system designed from published guidelines. Following a review of 44 published manuscripts and one unpublished report, 80 candidate gene variants and 173 polymorphisms were analysed among 1046 cases and 2310 controls. Majority of studies were of intermediate quality. Four polymorphisms with > 3 separate studies were included in the meta-analysis [OGG1 (rs1052133), TP53 (rs1042522), CYP1A1 (rs1048943) and GSTM1 Null polymorphism]. The meta-analysis demonstrated no significant associations of any of the above polymorphisms with GBC susceptibility. To conclude, existing candidate gene studies in GBC susceptibility have so far been insufficient to confirm any association. Future research should focus on a more comprehensive approach utilizing potential gene–gene, gene–environment interactions and high-risk haplotypes.