Understanding evolution of SARS-CoV-2: A perspective from analysis of genetic diversity of RdRp gene

Coronavirus disease 2019 emerged as the first example of “Disease X”, a hypothetical disease of humans caused by an unknown infectious agent that was named as novel coronavirus and subsequently designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The origin of the outbreak at the animal market in Wuhan, China implies it as a case of zoonotic spillover. The study was designed to understand evolution of Betacoronaviruses and in particular diversification of SARS-CoV-2 using RNA dependent RNA polymerase (RdRp) gene, a stable genetic marker. Phylogenetic and population stratification analyses were carried out using maximum likelihood and Bayesian methods, respectively. Molecular phylogeny using RdRp showed that SARS-CoV-2 isolates cluster together. Bat-CoV isolate RaTG13 and Pangolin-CoVs are observed to branch off prior to SARS-CoV-2 cluster. While SARS-CoV form a single cluster, Bat-CoVs form multiple clusters. Population-based analyses revealed that both SARS-CoV-2 and SARS-CoV form separate clusters with no admixture. Bat-CoVs were found to have single and mixed ancestry and clustered as four sub-populations. Population-based analyses of Betacoronaviruses using RdRp revealed that SARS-CoV-2 is a homogeneous population. SARS-CoV-2 appears to have evolved from Bat-CoV isolate RaTG13, which diversified from a common ancestor from which Pangolin-CoVs have also evolved. The admixed Bat-CoV sub-populations indicate that bats serve as reservoirs harboring virus ensembles that are responsible for zoonotic spillovers such as SARS-CoV and SARS-CoV-2. The extent of admixed isolates of Bat-CoVs observed in population diversification studies underline the need for periodic surveillance of bats and other animal reservoirs for potential spillovers as a measure towards preparedness for emergence of zoonosis.     

Approaches towards endogenous pancreatic regeneration

The phenomenon of pancreatic regeneration in mammals has been well documented. It has been shown that pancreatic tissue is able to regenerate in several species of mammal after surgical insult. This tissue is also known to have the potential to maintain or increase its beta-cell mass in response to metabolic demands during pregnancy and obesity. Since deficiency in beta-cell mass is the hallmark of most forms of diabetes, it is worthwhile understanding pancreatic regeneration in the context of this disease. With this view in mind, this article aims to discuss the potential use in clinical strategies of knowledge that we obtained from studies carried out in animal models of diabetes. Approaches to achieve this goal involve the use of biomolecules, adult stem cells and gene therapy. Various molecules, such as glucagon-like peptide-1, beta-cellulin, nicotinamide, gastrin, epidermal growth factor-1 and thyroid hormone, play major roles in the initiation of endogenous islet regeneration in diabetes. The most accepted hypothesis is that these molecules stimulate islet precursor cells to undergo neogenesis or to induce replication of existing beta-cells, emphasizing the importance of pancreas-resident stem/progenitor cells in islet regeneration. Moreover, the potential of adult stem cell population from bone marrow, umbilical cord blood, liver, spleen, or amniotic membrane, is also discussed with regard to their potential to induce pancreatic regeneration.     

Risk of Urinary Tract Infection Symptoms after Posthysterectomy Cystoscopy with 50% Dextrose as Compared with Saline Cystoscopy with Indigo Carmine

Study ObjectiveCompare odds of postoperative urinary symptoms in women who had cystoscopy after benign laparoscopic hysterectomy with 50% dextrose and with normal saline solution with intravenous indigo carmine.DesignRetrospective cohort study.SettingTwo tertiary care centers.PatientsAll women who underwent benign laparoscopic hysterectomy and intraoperative cystoscopy carried out by a single surgeon.InterventionsWe compared postoperative urinary symptoms in patients who received 50% dextrose cystoscopy fluid (January 2016–June 2017) with those who received saline cystoscopy with intravenous indigo carmine (November 2013–April 2014).Measurements and Main ResultsA total of 96 patients had cystoscopy with 50% dextrose and 104 with normal saline with intravenous indigo carmine. Differences in baseline characteristics of the two groups of participants mainly reflected institutional population diversity: age (45.2 vs 41.9, p = .01), body mass index (26.9 vs 33.4, p <.01), race, current smoking status (1% vs 7.8%, p = .04), diabetes (2.1% vs 11.5%, p = .01), history of abdominal surgery (53.1% vs 74%, p <.01), hysterectomy type, receipt of intraoperative antibiotics (92.7% vs 100%, p <.01), recatheterization (10.4% vs 0%, p <.01), and removal of catheter on postoperative day 0 (66.7% vs 12.5%, p <.01). Urinary symptoms were similar for 50% dextrose and saline (12.5% vs 7.7%, p = .19). After adjusting for age, body mass index, race, diabetes, and day of catheter removal, there remained no significant differences in urinary symptoms between the groups (odds ratio 3.19 [95% confidence interval, 0.82–12.35], p = .09). One immediate bladder injury was detected in the saline group and 1 delayed lower urinary tract injury in the 50% dextrose group.ConclusionOverall, most women experienced no urinary symptoms after benign laparoscopic hysterectomy. There were no significant differences in postoperative urinary symptoms or empiric treatment of urinary tract infection after the use of 50% dextrose cystoscopy fluid as compared with normal saline. The previous finding of increased odds of urinary tract infection after dextrose cystoscopy may be due to use in a high-risk population.