Cognitive dysfunction associated with COVID-19: Prognostic role of circulating biomarkers and microRNAs.

COVID-19 is renowned as a multi-organ disease having subacute and long-term effects with a broad spectrum of clinical manifestations. The evolving scientific and clinical evidence demonstrates that the frequency of cognitive impairment after COVID-19 is high and it is crucial to explore more clinical research and implement proper diagnostic and treatment strategies. Several central nervous system complications have been reported as comorbidities of COVID-19. The changes in cognitive function associated with neurodegenerative diseases develop slowly over time and are only diagnosed at an already advanced stage of molecular pathology. Hence, understanding the common links between COVID-19 and neurodegenerative diseases will broaden our knowledge and help in strategizing prognostic and therapeutic approaches. The present review focuses on the diverse neurodegenerative changes associated with COVID-19 and will highlight the importance of major circulating biomarkers and microRNAs (miRNAs) associated with the disease progression and severity. The literature analysis showed that major proteins associated with central nervous system function, such as Glial fibrillary acidic protein, neurofilament light chain, p-tau 181, Ubiquitin C-terminal hydrolase L1, S100 calcium-binding protein B, Neuron-specific enolase and various inflammatory cytokines, were significantly altered in COVID-19 patients. Furthermore, among various miRNAs that are having pivotal roles in various neurodegenerative diseases, miR-146a, miR-155, Let-7b, miR-31, miR-16 and miR-21 have shown significant dysregulation in COVID-19 patients. Thus the review consolidates the important findings from the numerous studies to unravel the underlying mechanism of neurological sequelae in COVID-19 and the possible association of circulatory biomarkers, which may serve as prognostic predictors and therapeutic targets in future research.

Pain as a determinant of health-related quality of life in patients with carpal tunnel syndrome; a case-controlled study.

Introduction: Carpal tunnel syndrome (CTS) is an entrapment neuropathy accounting for up to 90% of nerve compression syndromes. It causes both positive and negative symptoms in the hands. These symptoms, especially pain, can be debilitating, which can in turn have a negative effect on patients' quality of life (QoL). The aim of this cross-sectional case-controlled study was two-fold; to compare the QoL of patients with CTS and subjects without CTS and to determine the effect of pain on QoL in patients with CTS.Methods: All patients underwent nerve conduction studies (NCS) and were classified into mild, moderate, severe. QoL was assessed via the SF-36 questionnaire.Results: Fifty-one patients and 45 age- and gender-matched controls were recruited. Prevalence of pain (determined as scoring 4 or above on a visual analog scale) in CTS was 39.2%. CTS patient health-related QOL scores were significantly reduced (p < 0.001) across all of the SF-36 domains, compared to the healthy control group scores. After adjusting for gender presence of pain was still significantly negatively correlated with scores for physical functioning (beta -0.283, p = 0.036).Conclusions: Patients with CTS have a significantly worse QoL compared to subjects without CTS. In addition, the presence of pain is a significant determinant of physical functioning in patients who have been diagnosed with CTS.

T-cadherin gene variants are associated with nephropathy in subjects with type 1 diabetes.

BACKGROUND: High plasma adiponectin levels are associated with diabetic nephropathy (DN). T-cadherin gene (CDH13) variants have been shown to be associated with adiponectin levels. We investigated associations between allelic variations of CDH13 and DN in subjects with type 1 diabetes. METHODS: Two CDH13 polymorphisms were analysed in 1297 Caucasian subjects with type 1 diabetes from the 'Survival Genetic Nephropathy' (SURGENE) (n = 340, 10-year follow-up), 'Genesis France-Belgium' (GENESIS) (n = 501, 5-year follow-up for n = 462) and 'Génétique de la Néphropathie Diabétique' (GENEDIAB) (n = 456, 9-year follow-up for n = 283) cohorts. Adiponectin levels were measured in plasma samples from GENESIS and GENEDIAB cohorts. RESULTS: Pooled analysis of GENEDIAB and GENESIS studies showed that baseline plasma adiponectin levels were higher in subjects with established/advanced DN at inclusion (P < 0.0001) and in subjects who developed end-stage renal disease (ESRD) at follow-up (P < 0.0001). The minor allele of rs3865188 was associated with lower adiponectin levels (P = 0.006). rs11646213 [odds ratio (OR) 1.47; 95% confidence interval (CI) 1.18-1.85; P = 0.0009] and rs3865188 (OR 0.71; 95% CI 0.57-0.90; P = 0.004) were associated with baseline prevalence of established/advanced DN. These polymorphisms were also associated with the risk of ESRD (0.006 < P < 0.03). The association between rs11646213 (but not rs3865188) and renal function remained significant after adjustment for plasma adiponectin. In SURGENE, rs11646213 [hazard ratio (HR) 1.69; 95% CI 1.01-2.71; P = 0.04] and rs3865188 (HR 0.74; 95% CI 0.55-0.99; P = 0.04) were associated with risk of renal events (defined as progression to more severe DN stages). CONCLUSIONS: Plasma adiponectin levels are associated with the prevalence of DN and the incidence of ESRD in patients with type 1 diabetes. CDH13 polymorphisms are also associated with the prevalence and incidence of DN, and with the incidence of ESRD in these patients. The association between CDH13 and DN may be due to pleiotropic effects, both dependent and independent of plasma adiponectin levels.

Plasma Dihydroceramides Are Diabetes Susceptibility Biomarker Candidates in Mice and Humans.

Plasma metabolite concentrations reflect the activity of tissue metabolic pathways and their quantitative determination may be informative about pathogenic conditions. We searched for plasma lipid species whose concentrations correlate with various parameters of glucose homeostasis and susceptibility to type 2 diabetes (T2D). Shotgun lipidomic analysis of the plasma of mice from different genetic backgrounds, which develop a pre-diabetic state at different rates when metabolically stressed, led to the identification of a group of sphingolipids correlated with glucose tolerance and insulin secretion. Quantitative analysis of these and closely related lipids in the plasma of individuals from two population-based prospective cohorts revealed that specific long-chain fatty-acid-containing dihydroceramides were significantly elevated in the plasma of individuals who will progress to diabetes up to 9 years before disease onset. These lipids may serve as early biomarkers of, and help identify, metabolic deregulation in the pathogenesis of T2D.

ABCG8 polymorphisms and renal disease in type 2 diabetic patients.

BACKGROUND AND AIM: Sterols, bile acids and their receptors have been involved in diabetic nephropathy. The ATP-binding cassette transporters G5 and G8 (ABCG5 and ABCG8) play an important role in intestinal sterol absorption and bile acid secretion. The aim of our study was to assess the associations between two ABCG8 coding polymorphisms, T400K and D19H, and the incidence of renal events in type 2 diabetic subjects. METHODS: Participants were the 3137 French type 2 diabetic subjects with micro- or macro-albuminuria from the genetic substudy of the DIABHYCAR trial. The mean duration of follow-up was 4years. Renal events were defined as a doubling of serum creatinine concentration or end-stage renal disease at follow-up. We then used a second population (DIAB2NEPHROGENE) of 2140 type 2 diabetic patients for the purpose of validation. RESULTS: In DIABHYCAR, the 400K allele was significantly associated with a higher risk of incident renal events in a multiple adjusted model (HR: 1.75 [95% CI 1.20-2.56], P=0.003). This association was still significant after further adjustments for baseline values of estimated glomerular filtration rate and urinary albumin excretion. In the validation population, the 400K allele was associated with the prevalence of end-stage renal disease (OR=2.01 [95% CI 1.15-3.54], P=0.015). No significant association was found between the D19H polymorphism and the risk of diabetic nephropathy. CONCLUSIONS: A polymorphism of the sterol transporter ABCG8 has been associated with the prevalence of end-stage renal disease and with the incidence of new renal events in type 2 diabetic patients.