Mosaic Recombination Inflicted Various SARS-CoV-2 Lineages to Emerge into Novel Virus Variants: a Review Update

Human Coronaviruses (hCoVs) belongs to the enormous and dissimilar family of positive-sense, non-segmented, single-stranded RNA viruses. The RNA viruses are prone to high rates of mutational recombination resulting in emergence of evolutionary variant to alter various features including transmissibility and severity. The evolutionary changes affect the immune escape and reduce effectiveness of diagnostic and therapeutic measures by becoming undetectable by the currently available diagnostics and refractory to therapeutics and vaccines. Whole genome sequencing studies from various countries have adequately reported mosaic recombination between different lineage strain of SARS-CoV-2 whereby RNA dependent RNA polymerase (RdRp) gene reconnects with a homologous RNA strand at diverse position. This all lead to evolutionary emergence of new variant/ lineage as evident with the emergence of XBB in India at the time of writing this review. The continuous periodical genomic surveillance is utmost required for understanding the various lineages involved in recombination to emerge into hybrid variant. This may further help in assessing virus transmission dynamics, virulence and severity factor to help health authorities take appropriate timely action for prevention and control of any future COVID-19 outbreak.     

Preliminary studies on the detection ofMycobacterium avium-intracellulare complex using DNA probe from a clinical isolate

Genomic DNA from a clinical isolate ofMycobacterium avium-intracellulare complex was purified and cloned in PBR 322 at the tetracycline resistance site using Bam HI restriction enzyme. A 16 kb cloned fragment was purified, radiolabeled and used as a probe. Genomic DNA isolated from nineteen MAC strains, threeM. tuberculosis strains and oneM. kansasii strain were digested with Eco RI restriction enzyme, Southern blotted and hybridized with the 16 kb cloned and labeled fragment. Twelve MAC strains showed positive hybridization although five strains gave faint signals. Positive hybridization was noted in two out of the threeM. tuberculosis strains, possibly due to shared DNA homology. No signal was received from the singleM. kansasii strain used in this study.     

The effect of peer feedback for blogging on college students' reflective learning processes

Reflection is an important prerequisite to making meaning of new information, and to advance from surface to deep learning. Strategies such as journal writing and peer feedback have been found to promote reflection as well as deep thinking and learning. This study used an empirical design to investigate the interaction effects of peer feedback and blogging on college students' reflective thinking skills and their learning approaches. Forty-four first- and second-year undergraduate students participated in the study. Students kept blogs each week throughout a whole semester. Two journals were sampled at the beginning and end of the semester for each student. A repeated measure one-way ANOVA suggested that students' reflective thinking level increased significantly over time; however, peer feedback was found to negatively affect students' reflective thinking skills. The result of the study suggests more carefully designed uses in the future.     

A Narrative Review of Potential Future Antidiabetic Drugs: Should We Expect More?

Prevalence of diabetes mellitus, a chronic metabolic disease characterized by hyperglycemia, is growing worldwide. The majority of the cases belong to type 2 diabetes mellitus (T2DM). Globally, India ranks second in terms of diabetes prevalence among adults. Currently available classes of therapeutic agents are used alone or in combinations but seldom achieve treatment targets. Diverse pathophysiology and the need of therapeutic agents with more favourable pharmacokinetic-pharmacodynamics profile make newer drug discoveries in the field of T2DM essential. A large number of molecules, some with novel mechanisms, are in pipeline. The essence of this review is to track and discuss these potential agents, based on their developmental stages, especially those in phase 3 or phase 2. Unique molecules are being developed for existing drug classes like insulins, DPP-4 inhibitors, GLP-1 analogues; and under newer classes like dual/pan PPAR agonists, dual SGLT1/SGLT2 inhibitors, glimins, anti-inflammatory agents, glucokinase activators, G-protein coupled receptor agonists, hybrid peptide agonists, apical sodium-dependent bile acid transporter (ASBT) inhibitors, glucagon receptor antagonists etc. The heterogeneous clinical presentation and therapeutic outcomes in phenotypically similar patients is a clue to think beyond the standard treatment strategy.     

Reconvene and Reconnect the Antioxidant Hypothesis in Human Health and Disease

The antioxidants are essential molecules in human system but are not miracle molecules. They are neither performance enhancers nor can prevent or cure diseases when taken in excess. Their supplemental value is debateable. In fact, many high quality clinical trials on antioxidant supplement have shown no effect or adverse outcomes ranging from morbidity to all cause mortality. Several Chochrane Meta-analysis and Markov Model techniques, which are presently best available statistical models to derive conclusive answers for comparing large number of trials, support these claims. Nevertheless none of these statistical techniques are flawless. Hence, more efforts are needed to develop perfect statistical model to analyze the pooled data and further double blind, placebo controlled interventional clinical trials, which are gold standard, should be implicitly conducted to get explicit answers. Superoxide dismutase (SOD), glutathione peroxidase and catalase are termed as primary antioxidants as these scavenge superoxide anion and hydrogen peroxide. All these three enzymes are inducible enzymes, thereby inherently meaning that body increases or decreases their activity as per requirement. Hence there is no need to attempt to manipulate their activity nor have such efforts been clinically useful. SOD administration has been tried in some conditions especially in cancer and myocardial infarction but has largely failed, probably because SOD is a large molecule and can not cross cell membrane. The dietary antioxidants, including nutrient antioxidants are chain breaking antioxidants and in tandem with enzyme antioxidants temper the reactive oxygen species (ROS) and reactive nitrogen species (RNS) within physiological limits. Since body is able to regulate its own requirements of enzyme antioxidants, the diet must provide adequate quantity of non-enzymic antioxidants to meet the normal requirements and provide protection in exigent condition. So far, there is no evidence that human tissues ever experience the torrent of reactive species and that in chronic conditions with mildly enhanced generation of reactive species, the body can meet them squarely if antioxidants defense system in tissues is biochemically optimized. We are not yet certain about optimal levels of antioxidants in tissues. Two ways have been used to assess them: first by dietary intake and second by measuring plasma levels. Lately determination of plasma/serum level of antioxidants is considered better index for diagnostic and prognostic purposes. The recommended levels for vitamin A, E and C and beta carotene are 2.2–2.8 μmol/l; 27.5–30 μmol/l; 40–50 μmol/l and 0.4–0.5 μmol/l, respectively. The requirement and recommended blood levels of other dietary antioxidants are not established. The resolved issues are (1) essential to scavenge excess of radical species (2) participants in redox homeostasis (3) selective antioxidants activity against radical species (4) there is no universal antioxidant and 5) therapeutic value in case of deficiency. The overarching issues are (1) therapeutic value as adjuvant therapy in management of diseases (2) supplemental value in developing population (3) selective interactivity of antioxidant in different tissues and on different substrates (4) quantitative contribution in redox balance (5) mechanisms of adverse action on excess supplementation (6) advantages and disadvantages of prooxidant behavior of antioxidants (7) behavior in cohorts with polymorphic differences (8) interaction and intervention in radiotherapy, diabetes and diabetic complications and cardiovascular diseases (9) preventive behavior in neurological disorders (10) benefits of non-nutrient dietary antioxidants (11) markers to assess optimized antioxidants status (12) assessment of benefits of supplementation in alcoholics and heavy smokers. The unresolved and intriguing issues are (1) many compounds such as vitamin A and many others possessing both antioxidant and non-antioxidant properties contribute to both the activities in vivo or exclusively only to non-antioxidant activity and (2) since human tissues do not experience the surge of FR, whether there is any need to develop stronger synthetic antioxidants. Theoretically such antioxidants may do more harm than good.     

Comparative account of serum lipids,lipoproteins and apolipoprotein-B in patients of coronary artery disease

Serum total lipids (cholesterol and triglyceride), lipoproteins (VLDL, LDL and HDL) and Apolipoprotein-B levels of normal healthy individuals (n=25) and coronary artery disease patients (n=25) were estimated. The objective of the present study was to ascertain the role of apo-B in causation and inheritance of coronary artery disease. It was observed that on an average serum total cholesterol and triglyceride more than 200 mg/dl bring the individuals to a risk of coronary artery disease (CAD) irrespective of the age. CAD patients achieved this value at an early age (35–45 years). Similarly VLDL and LDL levels were found to be significantly raised in CAD patients when compared to that of age matched normal individuals, with patients achieving risk values at an early age. HDL levels were found to be significantly lower in CAD patients as compared to normal individuals. Serum apo-B levels were significantly raised in CAD patients as compared to age matched normal individuals. Patients with positive family history of CAD had raised serum apo-B levels than those having negative family history. A positive coefficient of correlation was observed between serum apo-B and LDL levels suggesting that more the number of Apo-B particles, more will be the synthesis of atherogenic particle (LDL). Patients with negative family history had serum apo-B levels closer to those of normal individuals and in these individuals HDL levels were found to be significantly lowered, suggesting that loss of scavenger role of HDL could be the risk factor responsible for the causation of CAD in these patients, with negative family history of coronary artery disease.     

Critical junctures in the development of university high-tech spinout companies

This paper investigates the development of university spinout companies (USOs). Employing a case-based research method, our study found that there are two important elements in their development. First, USOs go through a number of distinct phases of activity in their development. Each venture must pass through the previous phase in order to progress to the next one but each phase involves an iterative, non-linear process of development in which there may be a need to revisit some of the earlier decisions and activities. Second, at the interstices between the different phases of development we found that ventures face “critical junctures” in terms of the resources and capabilities they need to acquire to progress to the next phase. The different phases are critical as these ventures cannot develop into the next phase without overcoming each of the junctures. We identify four different critical junctures that spinout companies need to overcome if they are to succeed: opportunity recognition, entrepreneurial commitment, credibility and sustainability.     

External quality assessment for the RIA of thyroid related hormones: Second phase

An external quality assessment was conducted to assess the performance of various laboratories for RIA of thhyroid related hormones in two phases. In the first phase thirty five laboratories participated. At the end of first phase a meeting cum workshop was organised to discuss the results of first phase, difficultires faced by the participants and pinpoint the short oming. A second phase was then initiated with an objective of improvement in the performance, if any, where twelve samples from four pools were distributed to twenty four laboratories who participated for the second phase. The overall return of the results increased significantly from 71.8% (1586/2208) for the first phase to 92.4% (732/792) for the second phase. The inter laboratory %CV for T₃, T₄ and TSH were lower during the second phase (30.6%, 19.0% and 31.6% respectively) as compared to those observed during first phase (36.3%, 22.7% and 52.8% respectively). Similarly, there was an improvement in reproducibility of ALTM as %CV for T₃, T₄ and TSH decreased from 6.0%, 9.8% and 13.4% respectively to 4.5%, 4.6% and 8.5% respectively. The individual performances of the participating laboratories viz. bias, variability of bias and imprecision also showed a trend towards improvement as percent laboratories having desirable or acceptable results for T₃, T₄ and TSH increased from 10.7%, 60.7% and 0.0% respectively to 20.8%, 66.7% and 22.2% respectively. External quality assessment thus appears to be beneficial in assessing the performane of a laboratory in comfparison with other laboratories and indeed helps in improving the performance.     

Three dimensional couette flow and heat transfer through a porous medium with variable permeability

This paper reports research on the effects of variations in injection velocity and permeability on the heat transfer and flow through a highly porous medium between two horizontal parallel plates situated at constant distance with constant suction by the upper plate. Due to this type of variation in injection velocity and in permeability the flow becomes three dimensional. The governing equations are solved by adopting complex variable notations to obtain the expressions for the velocity and temperature field. The skin-friction along the main flow direction and rate of heat transfer are discussed with the help of graphs.