Applied genomics for identification of virulent biothreats and for disease outbreak surveillance.

Fortifying our preparedness to cope with biological threats by identifying and targeting virulence factors may be a preventative strategy for curtailing infectious disease outbreak. Virulence factors evoke successful pathogenic invasion, and the science and technology of genomics offers a way of identifying them, their agents and evolutionary ancestor. Genomics offers the possibility of deciphering if the release of a pathogen was intentional or natural by observing sequence and annotated data of the causative agent, and evidence of genetic engineering such as cloned vectors at restriction sites. However, to leverage and maximise the application of genomics to strengthen global interception system for real-time biothreat diagnostics, a complete genomic library of pathogenic and non-pathogenic agents will create a robust reference assembly that can be used to screen, characterise, track and trace new and existing strains. Encouraging ethical research sequencing pathogens found in animals and the environment, as well as creating a global space for collaboration will lead to effective global regulation and biosurveillance.

Expression, Interaction, and Role of Pseudogene Adh6-ps1 in Cancer Phenotypes.

Pseudogenes have been classified as functionless and their annotation is an ongoing problem. The Adh6-ps1-a mouse pseudogene belonging to the alcohol dehydrogenase gene complex (Adh) was analyzed to review the conservation, homology, expression, and interactions and identify any role it plays in disease phenotypes using bioinformatics databases. Results showed that Adh6-ps1 have 2 transcripts (processed and unprocessed) which may have emerged from a transposition and duplication event, respectively, and that induced inversions (Uox gene, In(3)11Rk) involving gene complexes associated with Adh6-ps1 have been implicated in a diverse range of diseases. Adh6-ps1 is highly conserved in vertebrates particularly rodents and expressed in the liver. The top 5 MirRNA targets were Mir455, Mir511, Mir1903, Mir361, and Mir669o markers. While much is unknown about Mir1903 and Mir669o, the silencing of Mir455 and Mir511 is linked with hepatocellular carcinoma (HCC), and Mir361 is implicated in endometrial cancers. Given the identified MirRNA interactions with Adh6-ps1 and its expression in HCC and reproductive systems, it may well have a role in tumorigenesis and disease phenotypes. Nonetheless, further studies are required to establish these facts to add to the growing efforts to understand pseudogenes and their potential involvement in disease conditions.

Identifying Glycemic Variability in Diabetes Patient Cohorts and Evaluating Disease Outcomes.

Glycemic variability (GV) is an obstacle to effective blood glucose control and an autonomous risk factor for diabetes complications. We, therefore, explored sample data of patients with diabetes mellitus who maintained better amplitude of glycemic fluctuations and compared their disease outcomes with groups having poor control. A retrospective study was conducted using electronic data of patients having hemoglobin A1C (HbA1c) values with five recent time points from Think Whole Person Healthcare (TWPH). The control variability grid analysis (CVGA) plot and coefficient of variability (CV) were used to identify and cluster glycemic fluctuation. We selected important variables using LASSO. Chi-Square, Fisher's exact test, Bonferroni chi-Square adjusted residual analysis, and multivariate Kruskal-Wallis tests were used to evaluate eventual disease outcomes. Patients with very high CV were strongly associated (p < 0.05) with disorders of lipoprotein (p = 0.0014), fluid, electrolyte, and acid-base balance (p = 0.0032), while those with low CV were statistically significant for factors influencing health status such as screening for other disorders (p = 0.0137), long-term (current) drug therapy (p = 0.0019), and screening for malignant neoplasms (p = 0.0072). Reducing glycemic variability may balance alterations in electrolytes and reduce differences in lipid profiles, which may assist in strategies for managing patients with diabetes mellitus.

Thyroid Tumor: Investigating MicroRNA-21 Gene Suppression in FTC and FTA.

The follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA) are malignant and benign thyroid neoplasms, respectively. MicroRNA (miRNA) expressions have been touted as an indicator for prognostic outcome in thyroid cancer. The study objective was to explore genes suppressed by miRNA-21-3p and miRNA-21-5p for potential therapeutic insights. Differentially expressed genes and their functional enrichment were obtained from 25 FTA and 27 FTC gene microarray dataset GSE82208 using R and Bioconductor tools. The miRNA target sites were obtained from miR-TarBase database. A unique gene list of differentially expressed FTC and FTA were entered into miR-TarBase database to obtain target genes for both miRNA-21-3p and miRNA-21-5p. The result showed that miRNA-21-3p and miRNA-21-5p downregulated TIMP3, MAT2A, TGFBR2, and PLAT gene in FTC and FTA leading to significant expression of acute phase-response to metallothionein, metal ions, and unfolded protein response (UPR). The computational analysis suggests that the suppression of miRNA-21-3p and miRNA-21-5p could be an intervention strategy for therapeutically targeting FTC and FTA treatments.

Frailty and the Risk of Polypharmacy in the Older Person: Enabling and Preventative Approaches.

Frail older people have an inherent risk of polypharmacy due to the need to treat multiple comorbidities, thus leading to various negative effects on their health due to the adverse actions from the drugs. This issue was discussed from a person-centered perspective, highlighting the category of frail older adults who are at a higher risk. Appropriate medication reconciliation in this population with useful prescribing tools (Beers and START/STOPP criteria) to minimize polypharmacy and to provide alternative prescriptive intervention could go alongside primary care to reduce the extent of frailty and polypharmacy. Reducing delayed referrals and extended hospitalization with electronic health record systems and using the signs of frailty from the Electronic Frailty Index (EFI) to predict polypharmacy for frail older persons are preventative approaches that proactively respond to frailty associated with the risk of polypharmacy.

Gene-Based Clustering Algorithms: Comparison Between Denclue, Fuzzy-C, and BIRCH.

The current study seeks to compare 3 clustering algorithms that can be used in gene-based bioinformatics research to understand disease networks, protein-protein interaction networks, and gene expression data. Denclue, Fuzzy-C, and Balanced Iterative and Clustering using Hierarchies (BIRCH) were the 3 gene-based clustering algorithms selected. These algorithms were explored in relation to the subfield of bioinformatics that analyzes omics data, which include but are not limited to genomics, proteomics, metagenomics, transcriptomics, and metabolomics data. The objective was to compare the efficacy of the 3 algorithms and determine their strength and drawbacks. Result of the review showed that unlike Denclue and Fuzzy-C which are more efficient in handling noisy data, BIRCH can handle data set with outliers and have a better time complexity.

Inflammatory Activities in Type 2 Diabetes Patients With Co-morbid Angiopathies and Exploring Beneficial Interventions: A Systematic Review.

Background: Diabetes is a long-term condition that can be treated and controlled but do not yet have a cure; it could be induced by inflammation and the goal of managing it is to prevent additional co-morbidities and reduce glycemic fluctuations. There is a need to examine inflammatory activities in diabetes-related angiopathies and explore interventions that could reduce the risk for future outcome or ameliorate its effects to provide insights for improved care and management strategies. Method: The study was conducted in Embase (1946-2020), Ovid Medline (1950-2020), and PubMed databases (1960-2020) using the PICO framework. Primary studies (randomized controlled trials) on type 2 diabetes mellitus and inflammatory activities in diabetes-related angiopathies were included. Terms for the review were retrieved from the Cochrane library and from PROSPERO using its MeSH thesaurus qualifiers. Nine articles out of 454 total hits met the eligibility criteria. The quality assessment for the selected study was done using the Center for Evidence-Based Medicine Critical Appraisal Sheet. Results: Data analysis showed that elevated CRP, TNF-α, and IL-6 were the most commonly found inflammatory indicator in diabetes-related angiopathies, while increased IL-10 and soluble RAGE was an indicator for better outcome. Use of drugs such as salsalate, pioglitazone, simvastatin, and fenofibrate but not glimepiride or benfotiamine reported a significant decrease in inflammatory events. Regular exercise and consumption of dietary supplements such as ginger, hesperidin which have anti-inflammatory properties, and those containing prebiotic fibers (e.g., raspberries) revealed a consistent significant (p < 0.05) reduction in inflammatory activities. Conclusion: Inflammatory activities are implicated in diabetes-related angiopathies; regular exercise, the intake of healthy dietary supplements, and medications with anti-inflammatory properties could result in improved protective risk outcome for diabetes patients by suppressing inflammatory activities and elevating anti-inflammatory events.

Multi-Morbidity in the Older Person: An Examination of Polypharmacy and Socioeconomic Status.

There has been increased focus on clinically managing multi-morbidity in the older population, but it can be challenging to find appropriate paradigm that addresses the socio-economic burden and risk for polypharmacy. The Commission on Social Determinants of Health (CSDH) has examined the need for institutional change and the parallel need to address the social causes of poor health. This study explored three potential interventions namely, meaningful information from electronic health records (EHR), social prescribing, and redistributive welfare policies from a person-centered perspective using the CARE (connecting, assessing, responding, and empowering) approach. Economic instruments that immediately redistribute state welfare and reduce income disparity such as direct taxation and conditional cash transfers could be adopted to enable older people with long-term conditions have access to healthcare services. Decreased socioeconomic inequality and unorthodox prescriptive interventions that reduce polypharmacy could mitigate barriers to effectively manage the complexities of multi-morbidity.