Single nucleotide polymorphisms (SNPs) at -238 and -308 positions in the TNFalpha promoter: clinical and bacteriological evaluation in leprosy

Tumor necrosis factor alpha (TNFalpha) plays a key role in orchestrating the complex events involved in inflammation and immune response. The presence of single nucleotide polymorphisms (SNPs) within the promoter region of the TNFa gene has been associated with a number of diseases. The aim of this study was to investigate the distribution of polymorphisms at positions -238 (G/A) and -308 (G/A) at the TNFalpha promoter, and its association to the outcome of different clinical forms of leprosy. Furthermore, the bacteriological index (BI) was evaluated among genotyped multibacillary (MB) patients in order to investigate the possible influence of each polymorphism on the bacterial load. This study included a total of 631 leprosy patients being 401 MB and 230 paucibacillary (PB), that was further separated according to its ethnicity (Afro- and Euro-Brazilians). The combination of SNPs in haplotypes generated three different arrangements: TNFG-G, TNFG-A and TNFA-G. In spite of the marked differences observed in the frequency of the haplotypes along the ethnic groups, no statistical differences were observed in haplotype frequencies between MB and PB patients. The BI analyses showed a lower bacteriological index among the -308 carriers, while the BI of the -238 carriers was higher. Although no significance has been achieved in this analysis regarding the influence of the polymorphisms to the development of the clinical outcome, it seems that in a different stage (among the MB patients) the polymorphisms could contribute to the degree of severity observed.     

Insight into prognostics,diagnostics, and management strategies for SARS CoV-2

The foremost challenge in countering infectious diseases is the shortage of effective therapeutics. The emergence of coronavirus disease (COVID-19) outbreak has posed a great menace to the public health system globally, prompting unprecedented endeavors to contain the virus. Many countries have organized research programs for therapeutics and management development. However, the longstanding process has forced authorities to implement widespread infrastructures for detailed prognostic and diagnostics study of severe acute respiratory syndrome (SARS CoV-2). This review discussed nearly all the globally developed diagnostic methodologies reported for SARS CoV-2 detection. We have highlighted in detail the approaches for evaluating COVID-19 biomarkers along with the most employed nucleic acid- and protein-based detection methodologies and the causes of their severe downfall and rejection. As the variable variants of SARS CoV-2 came into the picture, we captured the breadth of newly integrated digital sensing prototypes comprised of plasmonic and field-effect transistor-based sensors along with commercially available food and drug administration (FDA) approved detection kits. However, more efforts are required to exploit the available resources to manufacture cheap and robust diagnostic methodologies. Likewise, the visualization and characterization tools along with the current challenges associated with waste-water surveillance, food security, contact tracing, and their role during this intense period of the pandemic have also been discussed. We expect that the integrated data will be supportive and aid in the evaluation of sensing technologies not only in current but also future pandemics.

The foremost challenge in countering infectious diseases is the shortage of effective therapeutics.     

Evaluating Cardiovascular Safety of Novel Therapeutic Agents for the Treatment of Type 2 Diabetes Mellitus

Type 2 diabetes increases the risk of developing cardiovascular (CV) complications such as myocardial infarction, heart failure, stroke, peripheral vascular disease, and CV-associated mortality. Strict glycemic control in diabetics has shown improvement in microvascular complications related to diabetes but has been unable to demonstrate major effects on macrovascular complications including myocardial infarction and stroke. Conventional therapies for diabetes that include insulin, metformin, sulfonylureas (SU), and alpha-glucosidase inhibitors have limited and/or controversial data on CV safety based on observational studies not designed or powered to assess CV safety of these medications. In 2008, the US Food and Drug Administration (FDA) revised regulations for the approval of medications for type 2 diabetes by requiring that enough CV events are accrued prior to approval to rule out an upper 95 % confidence interval (95 % CI) for HR of 1.8 for CV events, followed by ruling out an upper 95 % CI for HR of 1.3 in the post-approval period. To date, novel diabetes therapies including peroxisome proliferator-activated receptor (PPAR) gamma agonists, dipeptidyl peptidase-4 (DPP4) inhibitors, glucagon-like peptide 1 (GLP 1) analogs, and sodium-glucose transporter-2 (SGL2) inhibitors have been evaluated in CV safety trials. Results from the first major CV outcome studies in type 2 diabetes, SAVOR-TIMI 53 and EXAMINE, have shown that neither saxagliptin nor alogliptin had increases in major CV events relative to placebo in high-risk patients. Ongoing and future trials will elucidate the CV safety for other DPP-4 inhibitors compared to SUs and the GLP-1 agonists versus placebo.     

Knowledge, attitudes and practices regarding gemstone therapeutics in a selected adult population in Pakistan

Background  

Gemstones have been in use as part of alternative and complementary medicine for years. However, our understanding of the perceived healing powers of gemstones is limited. An extensive literature search revealed that there is a dearth of validated information on this subject. This study was therefore undertaken to explore the various aspects of the knowledge, attitudes, and practices of the public towards gemstone therapeutics.