Long-term health consequences of COVID-19 in survivors hospitalised at a tertiary care hospital and their correlation with acute COVID-19 severity and associated risk factors.

OBJECTIVES: To determine post-COVID syndromes in the Indian population, correlating a wide spectrum of post-COVID manifestations with acute disease severity and associated risk factors. BACKGROUND: Post-COVID Syndrome (PCS) is defined as signs and symptoms that develop during or after acute COVID-19 infection. DESIGN OF STUDY: This is a prospective observational cohort with repetitive measurements. METHODS: The study followed RT-PCR confirmed COVID-19-positive survivors discharged from HAHC Hospital, New Delhi, for a period of 12 weeks. The patients were interviewed over the phone at 4 weeks and 12 weeks from the onset of symptoms for evaluation of clinical symptoms and health-related quality of life parameters. RESULTS: A total of 200 patients completed the study. At the baseline, 50% of the patients were categorised as severe based on their acute infection assessment. At 12 weeks after symptom onset, fatigue (23.5%), hair loss (12.5%) and dyspnea (9%) were the main persistent symptoms. The incidence of hair loss (12.5%), memory loss (4.5%) and brain fog (5%) were found to be increased as compared to the acute infection period. Severity of the acute COVID infection behaved as an independent predictor for the development of PCS, with high odds of experiencing persistent cough (OR = 13.1), memory loss (OR = 5.2) and fatigue (OR = 3.3). Further, 30% of subjects in the severe group experienced statistically significant fatigue at 12 weeks (p < .05). CONCLUSION: From the results of our study, it can be concluded that there is a huge disease burden of post-COVID Syndrome (PCS). The PCS comprised multisystem symptoms ranging from serious complaints of dyspnea, memory loss and brain fog to non-serious complaints of fatigue and hair loss. Severity of the acute COVID infection behaved as an independent predictor for the development of PCS. Our findings strongly recommend vaccination against COVID-19, for protection from disease severity as well as prevention of PCS. RELEVANCE TO CLINICAL PRACTICE: The findings of our study support the multidisciplinary approach required for the management of PCS with a team comprising of physicians, nurses, physiotherapists and psychiatrists working in close coordination for the rehabilitation of these patients. As nurses are considered the most trusted professionals in the community and the class of health workers associated with rehabilitation, focus should be given to educating them on PCS, which would prove to be an important strategy for efficient monitoring and long-term management of COVID-19 survivors.

A Phase 3, randomized, non-inferiority study of a heterologous booster dose of SARS CoV-2 recombinant spike protein vaccine in adults.

Due to waning immunity following primary immunization with COVID-19 vaccines, booster doses may be required. The present study assessed a heterologous booster of SII-NVX-CoV2373 (spike protein vaccine) in adults primed with viral vector and inactivated vaccines. In this Phase 3, observer-blind, randomized, active controlled study, a total of 372 adults primed with two doses of ChAdOx1 nCoV-19 (n = 186) or BBV152 (n = 186) at least six months ago, were randomized to receive a booster of SII-NVX-CoV2373 or control vaccine (homologous booster of ChAdOx1 nCoV-19 or BBV152). Anti-S IgG and neutralizing antibodies (nAbs) were assessed at days 1, 29, and 181. Non-inferiority (NI) of SII-NVX-CoV2373 to the control vaccine was assessed based on the ratio of geometric mean ELISA units (GMEU) of anti-S IgG and geometric mean titers (GMT) of nAbs (NI margin > 0.67) as well as seroresponse (≥ 2 fold-rise in titers) (NI margin -10%) at day 29. Safety was assessed throughout the study period. In both the ChAdOx1 nCoV-19 prime and BBV152 prime cohorts, 186 participants each received the study vaccines. In the ChAdOx1 nCoV-19 prime cohort, the GMEU ratio was 2.05 (95% CI 1.73, 2.43) and the GMT ratio was 1.89 (95% CI 1.55, 2.32) whereas the difference in the proportion of seroresponse was 49.32% (95% CI 36.49, 60.45) for anti-S IgG and 15% (95% CI 5.65, 25.05) for nAbs on day 29. In the BBV152 prime cohort, the GMEU ratio was 5.12 (95% CI 4.20, 6.24) and the GMT ratio was 4.80 (95% CI 3.76, 6.12) whereas the difference in the proportion of seroresponse was 74.08% (95% CI 63.24, 82.17) for anti-S IgG and 24.71% (95% CI 16.26, 34.62) for nAbs on day 29. The non-inferiority of SII-NVX-CoV2373 booster to the control vaccine for each prime cohort was met. SII-NVX-CoV2373 booster showed significantly higher immune responses than BBV152 homologous booster. On day 181, seroresponse rates were ≥ 70% in all the groups for both nAbs and anti-S IgG. Solicited adverse events reported were transient and mostly mild in severity in all the groups. No causally related SAE was reported. SII-NVX-CoV2373 as a heterologous booster induced non-inferior immune responses as compared to homologous boosters in adults primed with ChAdOx1 nCoV-19 and BBV152. SII-NVX-CoV2373 showed a numerically higher boosting effect than homologous boosters. The vaccine was also safe and well tolerated.

Safety and Immunogenicity of SARS-CoV-2 Recombinant Spike Protein Vaccine in Children and Adolescents in India: A Phase 2-3 Randomized Clinical Trial.

Importance: The recombinant COVID-19 vaccine NVX-CoV2373 has demonstrated efficacy of approximately 90% in adults; however, its safety and efficacy in children is unknown. Objective: To assess the noninferiority of SII-NVX-CoV2373 in children and adolescents compared to adults and to evaluate its safety in comparison with placebo. Design, Setting, and Participants: This phase 2-3 observer-blind randomized clinical trial was conducted in 2 cohorts, children (aged 2 to 11 years) and adolescents (aged 12 to 17 years) between August 2021 and August 2022. Participants were randomized 3:1 to SII-NVX-CoV2373 or placebo and monitored for 179 days. The participants, study team, and laboratory staff were blinded. This was a multicenter study conducted across 10 tertiary care hospitals in India. Exclusion criteria included previous COVID-19 infection or vaccination, immunocompromised condition, and immunosuppressive medications. Interventions: Two doses of 0.5-mL SII-NVX-CoV2373 or placebo were administered intramuscularly on days 1 and 22. Main Outcomes and Measures: Primary outcomes were geometric mean titer ratio of both anti-spike (anti-S) IgG and neutralizing antibodies (NAbs) between both pediatric age groups to that of adults on day 36. Noninferiority was concluded if the lower bound of 95% CI of this ratio was greater than 0.67 for each age group. Both the antibodies were assessed for the index strain and for selected variants at various time points. Solicited adverse events (AEs) were recorded for 7 days after each vaccination, unsolicited AEs were recorded for 35 days, and serious AEs and AEs of special interest were recorded for 179 days. Results: A total of 460 children in each age cohort were randomized to receive vaccine or placebo. The mean (SD) age was 6.7 (2.7) years in the child cohort and 14.3 (1.6) years in the adolescent cohort; 231 participants (50.2%) in the child cohort and 218 in the adolescent cohort (47.4%) were female. Both anti-S IgG and NAb titers were markedly higher in the SII-NVX-CoV2373 group than in the placebo group on both day 36 and day 180. The geometric mean titer ratios compared to those in adults were 1.20 (95% CI, 1.08-1.34) and 1.52 (95% CI, 1.38-1.67) for anti-S IgG in adolescents and children, respectively; while for NAbs, they were 1.33 (95% CI, 1.17-1.50) and 1.93 (95% CI, 1.70-2.18) in adolescents and children, respectively, indicating noninferiority. SII-NVX-CoV2373 also showed immune responses against variants studied. Injection site reactions, fever, headache, malaise, and fatigue were common solicited AEs. There were no AEs of special interest and no causally related serious AEs. Conclusions and Relevance: SII-NVX-CoV2373 was safe and well tolerated in children and adolescents in this study. The vaccine was highly immunogenic and may be used in pediatric vaccination against COVID-19. Trial Registration: Clinical Trials Registry of India Identifier: CTRI/2021/02/031554.

Safety and immunogenicity of SII-NVX-CoV2373 (COVID-19 vaccine) in adults in a phase 2/3, observer-blind, randomised, controlled study.

Background: NVX-CoV2373, a Covid-19 vaccine was developed in the USA with ∼90% efficacy. The same vaccine is manufactured in India after technology transfer (called as SII-NVX-CoV2373), was evaluated in this phase 2/3 immuno-bridging study. Methods: This was an observer-blind, randomised, phase 2/3 study in 1600 adults. In phase 2, 200 participants were randomized 3:1 to SII-NVX-CoV2373 or placebo. In phase 3, 1400 participants were randomized 3:1 to SII-NVX-CoV2373 or NVX-CoV2373 (940 safety cohort and 460 immunogenicity cohort). Two doses of study products (SII-NVX-CoV2373, NVX-CoV2373 or placebo) were given 3 weeks apart. Primary objectives were to demonstrate non-inferiority of SII-NVX-CoV2373 to NVX-CoV2373 in terms of geometric mean ELISA units (GMEU) ratio of anti-S IgG antibodies 14 days after the second dose (day 36) and to determine the incidence of causally related serious adverse events (SAEs) through 180 days after the first dose. Anti-S IgG response was assessed using an Enzyme-Linked Immunosorbent Assay (ELISA) and neutralizing antibodies (nAb) were assessed by a microneutralization assay using wild type SARS CoV-2 in participants from the immunogenicity cohort at baseline, day 22, day 36 and day 180. Cell mediated immune (CMI) response was assessed in a subset of 28 participants from immunogenicity cohort by ELISpot assay at baseline, day 36 and day 180. The total follow-up was for 6 months. Trial registration: CTRI/2021/02/031554. Findings: Total 1596 participants (200 in Phase 2 and 1396 in Phase 3) received the first dose. SII-NVX-CoV2373 was found non-inferior to NVX-CoV2373 (anti-S IgG antibodies GMEU ratio 0.91; 95% CI: 0.79, 1.06). At day 36, there was more than 58-fold rise in anti-S IgG and nAb titers compared to baseline in both the groups. On day 180 visit, these antibody titers declined to levels slightly lower than those after the first dose (13-22 fold-rise above baseline). Incidence of unsolicited and solicited AEs was similar between the SII-NVX-CoV2373 and NVX-CoV2373 groups. No adverse event of special interest (AESI) was reported. No causally related SAE was reported. Interpretation: SII-NVX-CoV2373 induced a non-inferior immune response compared to NVX-CoV2373 and has acceptable safety profile. Funding: SIIPL, Indian Council of Medical Research, Novavax.

Management of diabetic dyslipidemia in Indians: Expert consensus statement from the Lipid Association of India.

In 2021 an estimated 74 million individuals had diabetes in India, almost all type 2 diabetes. More than half of patients with diabetes are estimated to be undiagnosed and more 90% have dyslipidemia that is associated with accelerated development of atherosclerotic cardiovascular disease (ASCVD). Patients of Indian descent with diabetes have multiple features that distinguish them from patients with diabetes in Western populations. These include characteristics such as earlier age of onset, higher frequency of features of the metabolic syndrome, more prevalent risk factors for ASCVD, and more aggressive course of ASCVD complications. In light of the unique features of diabetes and diabetic dyslipidemia in individuals of Indian descent, the Lipid Association of India developed this expert consensus statement to provide guidance for management of diabetic dyslipidemia in this very high risk population. The recommendations contained herein are the outgrowth of a series of 165 webinars conducted by the Lipid Association of India across the country from May 2020 to July 2021, involving 155 experts in endocrinology and cardiology and an additional 2880 physicians.

Metformin alone and in combination with sitagliptin induces depression and impairs quality of life in type 2 diabetes mellitus patients: An observational study.

BACKGROUND: Various studies have reported the association of cognition and depression with diabetes. Literature suggests that metformin and sitagliptin used to control hyperglycemia in type 2 diabetes mellitus (T2DM) possess a beneficial effect on neurological symptoms associated with diabetes. However, there are scarce data in the clinical setting. Thus, this study aims to compare depression, cognitive impairment, and quality of life (QoL) of newly diagnosed T2DM patients with those of healthy individuals. Further, the impact of metformin alone or in combination with dipeptidyl peptidase-4 inhibitors on cognition, depression, and QoL of T2DM patients was also compared with newly diagnosed T2DM patients. MATERIALS AND METHODS: This was a prospective observational study in 120 subjects. The subjects were equally divided into four groups: healthy controls, newly diagnosed T2DM patients, and T2DM patients taking either metformin alone or in combination with sitagliptin. We assessed cognition using Mini-Mental State Examinations (MMSE), depression using Hamilton Depression Rating Scale (HAM-D), and health status using Short-Form Health Survey-36 (SF-36). RESULTS: No significant change in MMSE score was observed among the groups. However, a significant increase in the HAM-D score of newly diagnosed patients (p < 0.001), T2DM patients receiving metformin alone (p < 0.05), and in combination with sitagliptin (p < 0.001) was observed as compared to healthy controls (p < 0.001). Also, a statistically significant increase in HAM-D score was observed in patients receiving sitagliptin in combination with metformin as compared to metformin alone (p < 0.01). A decrease in SF-36 scores was observed in all groups as compared to healthy controls. CONCLUSION: To conclude, this preliminary study indicates that T2DM patients are most likely to suffer from depression and impaired QoL. Moreover, both the conventional and recent antidiabetic agents might lead to neurobehavioral complications and adverse impact on the QoL of these patients. Thus, we warrant the assessment of cognitive functions, depression, and QoL in patients receiving metformin and sitagliptin.

Genotypic characterization of vancomycin-resistant Enterococcus causing urinary tract infection in northern India.

Background & objectives: Infections caused by vancomycin-resistant Enterococci are difficult to treat given the limited therapeutic alternatives. Different gene clusters are known to confer vancomycin resistance. vanA and vanB genes are transferable and are clinically relevant. This cross-sectional study aimed to identify the vancomycin-resistant genotypes in the strains causing urinary tract infection and also to test the in vitro efficacy of linezolid and pristinamycin against the vancomycin-resistant isolates. Methods: Antimicrobial resistance profile of 118 enterococcal isolates was evaluated. Minimum inhibitory concentration of vancomycin, teicoplanin and high-level gentamicin (HLG) was determined by micro broth dilution. The vancomycin-resistant isolates were tested against linezolid and pristinamycin by micro-broth dilution and E strip method. The presence of vancomycin-resistant genes was detected by multiplex polymerase chain reaction and was sequenced and analyzed. Results: Most commonly isolated species were Enterococcus faecalis (76.9%) and Enterococcus faecium (16.9%). It was found that 43 per cent of the isolates were resistant to HLG and 16.9 per cent to vancomycin. Higher resistance was seen against fluoroquinolones, erythromycin, tetracycline and ß-lactam drugs. However, 5.08 per cent strains were resistant to tigecycline. All vancomycin-resistant strains were sensitive to pristinamycin and one was resistant to linezolid. vanA and vanB gene were found in 15 and five isolates, respectively. The gene sequences were submitted to NCBI gene bank and accession numbers were obtained. Interpretation & conclusions: The present study showed prevalence of vanA and vanB genes carrying Enterococcus in a tertiary care centre in north India. The emergence of resistance against drugs such as tigecycline and linezolid is a topic of concern as it will be a therapeutic challenge for physicians.

High-level gentamicin resistance mediated by Aac(6')-Ie-aph(2")-Ia gene in Enterococcus species isolated from clinical samples in Northern India.

CONTEXT: Enterococci are known to cause life-threatening infections which are difficult to treat as the organism harbors innate resistance to many antibiotics and can amass resistance toward many others through plasmid-mediated genetic exchange. AIMS: The study evaluates the drug susceptibility profile of various Enterococcus species isolated from various patient specimens submitted for bacteriological analysis and check the incidence of aac(6') Ie-aph(2") Ia gene. SETTING AND DESIGN: This in vitro cross-sectional study was executed at bacteriology laboratory of a 470 bedded hospital in New Delhi. MATERIALS AND METHODS: Drug susceptibility testing was carried out on enterococcal isolates. High-level gentamicin-resistant (HLGR) isolates detected by micro broth dilution assay were then subjected to molecular detection of aac(6') Ie-aph(2") Ia gene. STATISTICAL ANALYSIS USED: The level of significance was established by Chi-square test. RESULTS: Among the 182 enterococcal stains detected, 76.9% were Enterococcus faecalis and 20.3% were Enterococcus faecium. 12.08% strains were vancomycin resistant. 39% expressed resistance toward high-level gentamicin (HLG) and this finding was significantly higher in E. faecium than E. faecalis. HLGR strains expressed a higher degree of resistance to other drugs in contrast to non-HLGR isolates. In 67 out of 71 HLGR isolates the bifunctional gene was detected. CONCLUSION: Considerable presence of HLG and vancomycin resistance in the clinical isolates is alarming and should be taken seriously. The study shows high dissemination of aac(6')-Ie-aph(2")-Ia gene among Enterococci isolated from the region.

Trends in Practices of Self-Medication with Antibiotics among Medical Undergraduates in India.

Background: Self-medication with antibiotics (SMA) without the consultation of a professional is a serious health concern and can lead to serious health hazard. This study was designed to evaluate the trends in SMA behavior and risk factors in medical undergraduates to further explore the association between SMA practices and adverse drug events (ADEs). Materials and Methods: This cross-sectional questionnaire-based study was carried out among 360 volunteering medical undergraduates at a tertiary care teaching hospital in New Delhi. Results: 67.78% of students (244/360) gave a history of SMA practice with females dominating (54.09%). Out of 244 students giving a positive history of SMA, 182 (74.59%) experienced ADE, reflecting a strong positive association between the two. Convenience (86.07%) was observed to be the main reason of practicing SMA in this study. Over-the-counter sale of prescription-only drugs, namely antibiotics by the community pharmacies, is as high as 90.16%, leading to the main source of acquiring antibiotics for self-medication. Fever (47.54%) and respiratory infections (39.34%) emerged as the major indications for SMA. Extended-spectrum penicillins (60.66%) were the most commonly used class of antibiotics for SMA. Conclusion: Our findings endorse high SMA prevalence among Indian medical students. Strict regulations on antibiotic sales and public education reinforced by strong antibiotic stewardship program at all levels are highly recommended.

Metformin: Is It the Well Wisher of Bone Beyond Glycemic Control in Diabetes Mellitus?

Both diabetes mellitus and osteoporosis constitute a notable burden in terms of quality of life and healthcare costs. Diabetes mellitus affecting the skeletal system has been gaining attention in recent years and is now getting recognized as yet another complication of the disease, known as diabetic bone disease. As this condition with weaker bone strength increases fracture risk and reduces the quality of life, so much attention is being paid to investigate the molecular pathways through which both diabetes and its therapy are affecting bone metabolism. Out of many therapeutic agents currently available for managing diabetes mellitus, metformin is one of the most widely accepted first choices worldwide. The purpose of this review is to describe the effects of biguanide-metformin on bone metabolism in type 2 diabetes mellitus including its plausible mechanisms of action on the skeleton. In vitro studies suggest that metformin directly stimulates osteoblasts differentiation and may inhibit osteoclastogenesis by increasing osteoprotegerin expression, both through activation of the AMPK signaling pathway. Several studies in both preclinical and clinical settings report the favorable effects of metformin on bone microarchitecture, bone mineral density, bone turnover markers, and fracture risk. However, animal studies were not specific in terms of the diabetic models used and clinical studies were associated with several confounders. The review highlights some of these limitations and provide future recommendations for research in this area which is necessary to better understand the role of metformin on skeletal outcomes in diabetes.

Evaluation of Stress and Associated Biochemical Changes in Patients with Type 2 Diabetes Mellitus and Obesity.

PURPOSE: Type 2 diabetes mellitus (T2DM), a metabolic disorder, remains associated with a physiological impairment affecting large populations worldwide. Onset of T2DM is multifactorial where obesity and abnormal basal metabolic rate are considered most critical. Of people diagnosed with T2DM, about 80% are also obese. It is also reported that obese individuals have an increased odds of developing depression, whereas T2DM is estimated to increase the incidence by two-fold. The preponderance of research data demonstrates that T2DM alters the serum level of cortisol and adiponectin which are known to be associated with neuronal physiology. The study explored, how a metabolic disorder like T2DM is linked with the altered plasma level of cortisol and adiponectin, the risk factors for stress and depression. PATIENTS AND METHODS: A cross-sectional population study was conducted in T2DM patients using a bimodal approach. First approach used questionnaires, (1) Patient Health Questionnaire (PHQ-9) and (2) Stress Coping Inventory Questionnaire (SCQ) to assess signs and symptoms of depression and stress, respectively, in T2DM patients. In the second approach, robust biochemical analysis was conducted for serum adiponectin and cortisol levels. RESULTS: An association of T2DM in stress and depression was evaluated in 158 subjects (105 T2DM obese patients and 53 healthy controls). A lower PHQ-9 score and adiponectin levels were seen in T2DM obese patients compared to healthy controls (p<0.05). Further, results also depicted a lower adiponectin levels in T2DM obese patients with depression compared to T2DM obese patients without depression (p<0.05). The study did not find a significant difference in cortisol serum levels among the T2DM and control groups. However, a higher level of serum cortisol was reported in T2DM obese patients with depression over those T2DM obese patients who lacked depression (p<0.05). CONCLUSION: The findings suggest that T2DM obese patients might have a higher risk of developing stress and depression. Further, biochemical parameters, adiponectin and cortisol, might be the potential biomarkers for T2DM and may help in early diagnosis of these comorbid conditions.

Biofilm synthesis and other virulence factors in multidrug-resistant uropathogenic enterococci isolated in Northern India.

Purpose: Enterococci express high degree of resistance towards wide range of antibiotics. Production of biofilm and many virulence factors along with drug resistance makes it difficult to eradicate the infection from urinary tract. The present study detected the expression of such factors including biofilm production by multidrug-resistant (MDR) enterococci. Materials and Methods: Drug susceptibility of 103 uropathogenic enterococci was performed followed by estimation of minimum inhibitory concentration of high-level gentamicin and vancomycin by microbroth dilution method. Vancomycin-resistant genes were detected by multiplex polymerase chain reaction. Production of virulence factors such as haemagglutination, caseinase, lipase, gelatinase, haemolysin and ß-lactamase was detected by phenotypic methods in MDR strains. Biofilm production was detected by calcofluor-white fluorescence staining and semi-quantitative adherence assay. Results: 45% and 18.4% of the isolates were high-level gentamicin-resistant and vancomycin-resistant enterococci (VRE), respectively. vanA gene was detected in 14 and vanB gene in 5 strains. Biofilm, caseinase and gelatinase were the most expressed virulence factor. Expression of caseinase, gelatinase and lipase was significantly higher in Enterococcus faecalis (P < 0.05). Expression of haemagglutination, gelatinase and haemolysin among the vancomycin-resistant isolates was significantly higher (P < 0.05). Conclusion: VanA and vanB are the prevalent genotypes responsible for vancomycin resistance. The high prevalence of MDR enterococcal strains producing biofilm and virulence determinants raises concern. asa1, hyl, esp, gelE, cyl and other genes are known to express these factors and contribute to biofilm formation. Most uropathogenic enterococci expressed biofilm at moderate level and can be detected effectively by calcofluor-white staining. No correlation was noted between vancomycin resistance and biofilm production.

Increased serum interleukin-9 and interleukin-1ß are associated with depression in type 2 diabetes patients.

BACKGROUND: Co-morbid diabetes and depression are prevalent chronic conditions negatively affecting quality of life (QoL). Inflammation has been considered as an integral mechanism in patients with both diabetes and depression. OBJECTIVE: The aim of the present study was to investigate depression and its association with interleukins (IL)-1ß and IL-9 in type 2 diabetic patients (T2DM) and controls. The QoL in diabetic patient was also assessed. METHODS: Eighty subjects were included, distributed among three groups: Group 1 - Healthy controls; Group 2 - T2DM patients without depression; Group 3 - T2DM patients with depression. Depression and QoL were assessed using Patient Health Questionnaire (PHQ-9) and The Audit of Diabetes-Dependent QoL (ADDQoL), respectively. IL-1ß and IL-9 were measured in serum samples of all the patients using ELISA kit. RESULTS: The PHQ score in the Group 3 was significantly higher as compared to Group 1. The ADDQoL scores in the Group 3 were significantly higher as compared to Group 2. Levels of IL-9 and IL-1ß were elevated in Group 3, as compared to the other groups. CONCLUSION: This study showed positive association between depression and IL-1ß, IL-9 in T2DM patients. Additionally, the diabetic patients have poorer quality of life, which is further worsened by the presence of depression. Thus, routine assessment for the presence of depression is suggested in T2DM patients.

Methylglyoxal and soluble RAGE in type 2 diabetes mellitus: Association with oxidative stress.

PURPOSE: Methylglyoxal (MGO) and MGO related advance end product (AGE) are thought to contribute to the development of diabetes and its complications. The present study was intended to determine plasma MGO and sRAGE levels in T2DM patients and to assess the relationship between MGO and other parameters, such as sRAGE and oxidative markers. METHODS: The study was carried out in 100 control and T2DM subjects. Methylglyoxal, sRAGE, HbA1c, and other markers were measured by using a standard protocol and the relationship between variables was analyzed using Spearman's correlation analysis. RESULTS: Plasma MGO levels in patients with T2DM (221.1 ± 9.50 ng/mL) were significantly higher than in control subjects (121.1 ± 6.52 ng/mL, P < 0.001). The plasma level of MGO was positively correlated with glycosylated hemoglobin (HbA1c, r = 0.50, P < 0.001). Plasma soluble form of RAGE (sRAGE) was significantly decreased in T2DM subjects (5.3 ± 0.64 ng/mL) as compared to the control group (7.7 ± 0.86 ng/mL, p < 0.05). However, at increased level of glycation (HbA1c > 10%), the sRAGE level was 6.2 ± 0.42 ng/mL and was not statistically significant as compared to control healthy group (> 0.05). Moreover, we have not found any correlation between MGO and other markers (p > 0.05). CONCLUSIONS: The findings of the present study showed that increased plasma MGO level is significantly associated with the HbA1c levels in T2DM patients. Moreover, the study shows that plasma sRAGE level is significantly augmented at increased level of glycation (HbA1c > 10%) in T2DM patients.

Increased serum interleukin-9 and interleukin-1β are associated with depression in type 2 diabetes patients / Interleucina-9 e interleucina-1β séricas aumentadas estão associadas à depressão em pacientes com diabetes tipo 2

ABSTRACT Background: Co-morbid diabetes and depression are prevalent chronic conditions negatively affecting quality of life (QoL). Inflammation has been considered as an integral mechanism in patients with both diabetes and depression. Objective: The aim of the present study was to investigate depression and its association with interleukins (IL)-1β and IL-9 in type 2 diabetic patients (T2DM) and controls. The QoL in diabetic patient was also assessed. Methods: Eighty subjects were included, distributed among three groups: Group 1 - Healthy controls; Group 2 - T2DM patients without depression; Group 3 - T2DM patients with depression. Depression and QoL were assessed using Patient Health Questionnaire (PHQ-9) and The Audit of Diabetes-Dependent QoL (ADDQoL), respectively. IL-1β and IL-9 were measured in serum samples of all the patients using ELISA kit. Results: The PHQ score in the Group 3 was significantly higher as compared to Group 1. The ADDQoL scores in the Group 3 were significantly higher as compared to Group 2. Levels of IL-9 and IL-1β were elevated in Group 3, as compared to the other groups. Conclusion: This study showed positive association between depression and IL-1β, IL-9 in T2DM patients. Additionally, the diabetic patients have poorer quality of life, which is further worsened by the presence of depression. Thus, routine assessment for the presence of depression is suggested in T2DM patients.

RESUMO Introdução: O diabetes e a depressão comórbidas são condições crônicas prevalentes que afetam negativamente a qualidade de vida (QdV). A inflamação tem sido considerada como um mecanismo integral em pacientes com diabetes e depressão. Objetivo: Investigar a depressão e sua associação com interleucinas (IL)-1β e IL-9 em pacientes diabéticos tipo 2 (DM2) e controles. A QdV em diabéticos também foi avaliada. Métodos: Foram incluídos 80 indivíduos, divididos em três grupos: Grupo 1 - controles saudáveis; Grupo 2 - pacientes com DM2 sem depressão; Grupo 3 - pacientes com DM2 com depressão. A depressão e a QdV foram avaliadas usando o Questionário de Saúde do Paciente (Patient Health Questionnaire - PHQ-9) e a auditoria de QdV dependente de diabetes (Audit of Diabetes-Dependent Quality of Life - ADDQoL), respectivamente. IL-1β e IL-9 foram medidas em amostras de soro de todos os pacientes utilizando kit de ELISA. Resultados: O escore do PHQ no grupo 3 foi significativamente maior em comparação ao grupo 1. Os escores de ADDQoL no grupo 3 foram significativamente maiores em comparação ao grupo 2. Os níveis de IL-9 e IL-1β foram elevados no grupo 3, como em comparação com os outros grupos. Conclusão: Este estudo mostrou associação positiva entre depressão e IL-1β, IL-9 em pacientes com DM2. Além disso, os pacientes diabéticos têm pior QdV, o que é ainda piorado pela presença de depressão. Assim, a avaliação rotineira da presença de depressão é sugerida em pacientes com DM2.

Emerging genetic diversity among clinical isolates of SARS-CoV-2: Lessons for today.

Considering the current pandemic of COVID-19, it is imperative to gauge the role of molecular divergence in SARS-CoV-2 with time, due to clinical and epidemiological concerns. Our analyses involving molecular phylogenetics is a step toward understanding the transmission clusters that can be correlated to pathophysiology of the disease to gain insight into virulence mechanism. As the infections are increasing rapidly, more divergence is expected followed possibly by viral adaptation. We could identify mutational hotspots which appear to be major drivers of diversity among strains, with RBD of spike protein emerging as the key region involved in interaction with ACE2 and consequently a major determinant of infection outcome. We believe that such molecular analyses correlated with clinical characteristics and host predisposition need to be evaluated at the earliest to understand viral adaptability, disease prognosis, and transmission dynamics.

A survey of fasting practices and acceptance of an intervention for achieving control in diabetes during Ramadan.

Background: Many people with diabetes, who practise Islam, are passionate about fasting during Ramadan despite their medical condition and exemption from the religion. These patients are at risk of hypoglycaemia, hyperglycaemia, diabetic ketoacidosis, dehydration and thrombosis. We evaluated the acceptability of an individualized management plan for such people. Methods: We conducted a survey to assess the knowledge and ability of patients to manage their diabetes while observing the fast during Ramadan. Then, the acceptance of an educational intervention was assessed among patients, which was provided 1 month before Ramadan. Patients were followed up at 2 weeks into and after Ramadan. Results: Of the survey population, only 14.7% of patients volunteered for pre-Ramadan assessment and 97.5% of patients recollected suffering from symptoms suggestive or hypoglycaemia or hyperglycaemia. Following the intervention, 17 of 50 patients did not fast; 26 patients followed dietary advice, while 7 patients did not. Symptoms suggestive of hypoglycaemia and hyperglycaemia were reported by 21 of 33 patients who fasted and 21 of 28 patients reported lower body weight. Insulin and hypoglycaemic drugs were changed from morning to evening dosing in 41% of patients while 18% of patients had their drugs stopped. Conclusion: An educational intervention generated awareness among the patients and helped 43 of 50 patients in making rational decisions about control of diabetes during Ramadan.

Evaluation of Autonomic Dysfunction in Obese and Non-Obese Hypertensive Subjects.

INTRODUCTION: Obesity and more specifically, visceral obesity, has been consistently associated with hypertension and increased cardiovascular risk. Epidemiological studies indicate that at least two-third of the prevalence of hypertension can be directly attributed to obesity. Studies also suggest that hypertensive patients have impaired cardiac autonomic function. AIM: The objective of the study was to examine any added effects of obesity on cardiac autonomic dysfunction in hypertensive patients. MATERIALS AND METHODS: Hypertensive subjects (n=45) between 35-60 years of age were divided into two groups; Group A (n=30) consisted of non-obese hypertensive subjects and Group B (n=15) consisted of obese (BMI≥30kg/m(2)) hypertensive subjects. Cardiac autonomic function was assessed using four tests - Heart rate response to immediate standing (30:15 ratio), standing to lying ratio (S/L ratio), Blood pressure response to immediate standing and Cold Pressor Test (CPT). RESULTS: There were no significant differences for autonomic function tests between obese and non-obese hypertensive subjects (p >0.05). CONCLUSION: The results showed that there are no significant differences in the cardiac autonomic function responses between obese and non-obese hypertensive subjects.