Inclusion in the World Health Organization model list of essential medicines of non-vitamin K anticoagulants for treatment of non-valvular atrial fibrillation: a step towards reducing the burden of cardiovascular morbidity and mortality

Non-vitamin K antagonist oral anticoagulants (NOACs) represent a paradigm shift in the treatment of non-valvular atrial fibrillation (AF) with major practice guidelines around the world recommending NOACs over vitamin K antagonist oral anticoagulants for initial treatment of AF for stroke prevention. Here we describe the evidence collated and the process followed for the successful inclusion of NOACs into the 21st WHO Model List of Essential Medicines (EML). Individual NOACs have been reported to be non-inferior or superior to warfarin in preventing stroke and systemic embolism in eligible AF patients with a reduction in the risk of stroke and systemic embolism and a lower risk of major bleeding in patients with non-valvular AF compared with warfarin in both RCTs and real-world data. The successful inclusion of NOACs in the WHO EML is an important step forward in the global fight against cardiovascular morbidity and mortality, especially in low- and middle-income countries, where the burden of disease is high and limited access to diagnosis and treatment translates into a higher burden of morbidity, mortality, and economic costs

Oral health knowledge, attitudes and practices of people living with diabetes in South Asia : a scoping review

Diabetes increases the risk of oral health complications. This review aimed to synthesise the current evidence on the oral health knowledge, attitudes and practices of people living with diabetes in South Asian countries and provide recommendations on possible strategies for addressing the gaps in oral health care in this population, including the role of non-dental professionals. Using a scoping review framework, six electronic databases (Ovid Medline, CINAHL, ProQuest Central, Scopus, Web of Science and Embase) were searched to identify the relevant literature published between January 2000 and December 2021. The data were extracted into three main categories based on the review’s aims, and further refined into sub-categories. A total of 23 studies were included. The review identified that while people with diabetes living in South Asian countries had some level of awareness about oral health and limited care practices to maintain good oral health, there were gaps in knowledge, and there were areas where their oral health practices and attitudes could be improved. The findings suggest a need for developing targeted oral health policies as well as implementing integrated oral health care interventions involving non-dental professionals to improve the oral health outcomes of people with diabetes

Antiviral Activity of Some Plants Used in Nepalese Traditional Medicine

Methanolic extracts of 41 plant species belonging to 27 families used in the traditional medicine in Nepal have been investigated for in vitro antiviral activity against Herpes simplex virus type 1 (HSV-1) and influenza virus A by dye uptake assay in the systems HSV-1/Vero cells and influenza virus A/MDCK cells. The extracts of Astilbe rivularis, Bergenia ciliata, Cassiope fastigiata and Thymus linearis showed potent anti-herpes viral activity. The extracts of Allium oreoprasum, Androsace strigilosa, Asparagus filicinus, Astilbe rivularis, Bergenia ciliata and Verbascum thapsus exhibited strong anti-influenza viral activity. Only the extracts of A. rivularis and B. ciliata demonstrated remarkable activity against both viruses

HDAC6 Inhibitors Modulate Lys49 Acetylation and Membrane Localization of β-Catenin in Human iPSC-Derived Neuronal Cells

We examined the effects of isoform-specific histone deacetylase (HDAC) inhibitors on β-catenin posttranslational modifications in neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (iPSCs). β-catenin is a multifunctional protein with important roles in the developing and adult central nervous system. Activation of the Wnt pathway results in stabilization and nuclear translocation of β-catenin, resulting in activation of multiple target genes. In addition, β-catenin forms a complex with cadherins at the plasma membrane as part of the adherens junctions. The N-terminus of β-catenin has phosphorylation, ubiquitination, and acetylation sites that regulate its stability and signaling. In the absence of a Wnt signal, Ser33, Ser37, and Thr41 are constitutively phosphorylated by glycogen synthase kinase 3β (GSK3β). β-Catenin phosphorylated at these sites is recognized by β-transducin repeat-containing protein (βTrCP), which results in ubiquitination and degradation by the ubiquitin-proteasome pathway. The N-terminal regulatory domain of β-catenin also includes Ser45, a phosphorylation site for Casein Kinase 1α (CK1α) and Lys49, which is acetylated by the acetyltransferase p300/CBP-associated factor (PCAF). The relevance of Lys49 acetylation and Ser45 phosphorylation to the function of β-catenin is an active area of investigation. We find that HDAC6 inhibitors increase Lys49 acetylation and Ser45 phosphorylation but do not affect Ser33, Ser37, and Thr41 phosphorylation. Lys49 acetylation results in decreased ubiquitination of β-catenin in the presence of proteasome inhibition. While increased Lys49 acetylation does not affect total levels of β-catenin, it results in increased membrane localization of β-catenin

The Risk Factors of Seasonal Hyperacute Panuveitis

Background: Seasonal Hyperacute Panuveitis (SHAPU) is an eye disease of unclear aetiology occurring cyclically during the autumn in odd years in Nepal causing blindness within a week. This study is the first of its type to investigate the risk factors of SHAPU. Methods: A multicentric national level case–control study was performed during the 2017 SHAPU outbreak. Cases were matched to controls in a 1:3 ratio based on age, sex and geographic area. Questionnaire-based personal interview was used and risk factors were categorized as biological and behavioral. For univariate analysis, frequency, median and interquartile range was calculated. Chi-squared test with/without continuity correction and Fisher’s exact test were used. Multivariate conditional logistic regressions were used for all the independent variables for p <0.1 in the univariate analyses. Results: We identified 35 cases and 105 controls; 71.4% were children≤16 years (38-day infant to 50-year-old). All were immunocompetent individuals, males were 57.1% and females 42.9%. Potential risks such as visible moths/butterfly activity, contact with livestock, and attending mass gatherings of people were not reported more frequently in cases vs controls in univariate analyses. Differences in possibly protective factors such as self-reported mosquito net use, light off at night while sleeping, and habit of hands/face washing after physical contact/touch with any insects/butterflies/birds were not statistically significant between both groups. In multivariate model, SHAPU cases were significantly more likely than controls to report physical contact with butterflies/white moths (Adjusted OR:6.89; CI:2.79–17.01,p < .001). Conclusions: Direct physical contact with butterflies/moths was associated with significantly increased odds of SHAPU cases