Shorter telomere length, higher telomerase activity in association with tankyrase gene polymorphism contribute to high-altitude pulmonary edema.

High-altitude pulmonary edema (HAPE) is a noncardiogenic form of pulmonary edema, which is induced upon exposure to hypobaric hypoxia at high altitude (HA). Hypobaric hypoxia generates reactive oxygen species that may damage telomeres and disturb normal physiological processes. Telomere complex comprises of multiple proteins, of which, tankyrase (TNKS) is actively involved in DNA damage repairs. We hence investigated the association of TNKS and telomeres with HAPE to delineate their potential role at HA. The study was performed in three groups, High-altitude pulmonary edema patients (HAPE-p, n = 200), HAPE-resistant sojourners (HAPE-r, n = 200) and highland permanent healthy residents (HLs, n = 200). Variants of TNKS were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Plasma TNKS level was estimated using enzyme-linked immunosorbent assay, expression of TNKS and relative telomere length were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and telomerase activity was assessed by the telomere repeat amplification protocol assay. TNKS poly-ADP ribosylates the telomere-repeat factor (TRF), which is a negative regulator of telomere length. Consequently, TRF expression was also measured by RT-qPCR. The TNKS heterozygotes rs7015700GA were prevalent in HLs compared to the HAPE-p and HAPE-r. The plasma TNKS was significantly decreased in HAPE-p than HAPE-r (P = 0.006). TNKS was upregulated 9.27 folds in HAPE-p (P = 1.01E-06) and downregulated in HLs by 3.3 folds (P = 0.02). The telomere length was shorter in HAPE-p compared to HAPE-r (P = 0.03) and HLs (P = 4.25E-4). The telomerase activity was significantly higher in HAPE-p compared to both HAPE-r (P = 0.01) and HLs (P = 0.001). HAPE-p had the lowest TNKS levels (0.186 ± 0.031 ng/µl) and the highest telomerase activity (0.0268 amoles/µl). The findings of the study indicate the association of TNKS and telomeres with HA adaptation/maladaptation.

Identifying putative cerebrospinal fluid biomarkers of amyotrophic lateral sclerosis in a north Indian population.

INTRODUCTION: Evidence-based information about cerebrospinal fluid (CSF) levels of biomarkers in patients with amyotrophic lateral sclerosis (ALS) is limited. METHODS: Vascular endothelial growth factor (VEGF) and its receptor vascular endothelial growth factor receptor 2 (VEGFR2), optineurin (OPTN), monocyte chemoattractant protein-1 (MCP-1), angiogenin (ANG), and TAR DNA-binding protein (TDP-43) were quantified by enzyme-linked immunoassay in the CSF of 54 patients with sporadic ALS and 32 controls in a case-control study design. RESULTS: CSF levels of VEGF (P = .014) and ANG (P = .009) were decreased, whereas VEGFR2 was higher (P = .002) in patients with ALS than in controls. TDP-43 positively correlated with MCP-1 (P = .003), VEGF (P < .001), and VEGFR2 (P < .001) in patients with ALS. DISCUSSION: Our findings suggest possible utility of VEGF, VEGFR2, and ANG as biomarkers for use in ALS treatment trials.

The Telomere-Telomerase System Is Detrimental to Health at High-Altitude.

The hypobaric-hypoxia environment at high-altitude (HA, >2500 m) may influence DNA damage due to the production of reactive molecular species and high UV radiation. The telomere system, vital to chromosomal integrity and cellular viability, is prone to oxidative damages contributing to the severity of high-altitude disorders such as high-altitude pulmonary edema (HAPE). However, at the same time, it is suggested to sustain physical performance. This case-control study, comprising 210 HAPE-free (HAPE-f) sojourners, 183 HAPE-patients (HAPE-p) and 200 healthy highland natives (HLs) residing at ~3500 m, investigated telomere length, telomerase activity, and oxidative stress biomarkers. Fluidigm SNP genotyping screened 65 single nucleotide polymorphisms (SNPs) in 11 telomere-maintaining genes. Significance was attained at p ≤ 0.05 after adjusting for confounders and correction for multiple comparisons. Shorter telomere length, decreased telomerase activity and increased oxidative stress were observed in HAPE patients; contrarily, longer telomere length and elevated telomerase activity were observed in healthy HA natives compared to HAPE-f. Four SNPs and three haplotypes are associated with HAPE, whereas eight SNPs and nine haplotypes are associated with HA adaptation. Various gene-gene interactions and correlations between/among clinical parameters and biomarkers suggested the presence of a complex interplay underlining HAPE and HA adaptation physiology. A distinctive contribution of the telomere-telomerase system contributing to HA physiology is evident in this study. A normal telomere system may be advantageous in endurance training.

Coping Strategy, Life Style and Health Status During Phase 3 of Indian National Lockdown for COVID-19 Pandemic-A Pan-India Survey.

The implementation of timely COVID-19 pan-India lockdown posed challenges to the lifestyle. We looked at the impact of lifestyle on health status during the lockdown in India. A self-rated scale, COVID Health Assessment Scale (CHAS) was circulated to evaluate the physical health or endurance, mental health i.e. anxiety and stress, and coping ability of the individuals under lockdown. This is a pan-India cross-sectional survey study. CHAS was designed by 11 experts in 3 Delphi rounds (CVR = 0.85) and was circulated through various social media platforms, from 9th May to 31st May 2020, across India by snowball circulation method. CHAS forms of 23,760 respondents were downloaded from the Google forms. Logistic regression using R software was used to compare vulnerable (>60 years and with chronic diseases) with non-vulnerable groups. There were 23,317 viable respondents. Majority of respondents included males (58·8%). Graduates/Postgraduates (72·5%), employed (33·0%), businessmen (6·0%), and professionals (9·7%). The vulnerable group had significantly (OR 1.31, p < 0.001) higher representation of overweight individuals as compared to non-vulnerable group. Regular use of tobacco (OR 1.62, p = 0.006) and other addictive substances (OR 1.80, p = 0.039) showed increased vulnerability. Respondents who consume junk food (OR 2.19, p < 0.001) and frequently snack (OR 1.16, p < 0.001) were more likely to be vulnerable. Respondents involved in fitness training (OR 0.57, p < 0.001) or did physical works other than exercise, yoga, walk or household activity (OR 0.88, p = 0.004) before lockdown were less likely to be vulnerable. Majority had a very good lifestyle, 94.4% never smoked or used tobacco, 92.1% were non-alcoholic, 97.5% never used addictive substances, 84.7% had good eating habits, 75.4% were vegetarians, 82.8% had "good" sleep, 71.7% did physical activities. Only 24.7% reported "poor" coping ability. Depression with somewhat low feeling were more likely to be vulnerable (OR 1.26, p < 0.001). A healthy lifestyle that includes healthy eating, proper sleep, physical activeness and non-addictive habits supports better coping ability with lesser psychological distress among Indian population during lockdown.

Effect of breathing intervention in patients with COVID and healthcare workers.

Background: Regulated breathing facilitates ventilation and reduces breathlessness. However, the effect of Yogic breathing on patients with COVID remains unclear. We aimed to evaluate the efficacy of two breathing protocols, i.e., short breathing technique (SBT) and long duration breathing technique (LBDT). Methods: Three groups including COVID-positive patients, COVID-recovered patients, and healthcare workers (HCWs) were included in the study and segregated into Yoga and control groups. SBT was administered to COVID-positive patients. Both SBT and LBDT were administered to COVID-recovered patients and HCWs. A total of 18 biochemical parameters, a 6-min walk test (6MWT), and a 1-min sit-stand test (1MSST) were assessed on 0th, 7th, and 15th days, where biochemical parameters were the primary outcome. Pre-post estimation of neuropsychological parameters (nine questionnaires) and heart rate variability (HRV) were carried out. The paired t-test or Wilcoxon rank test was applied for pre-post comparison and the Student's t-test or Mann-Whitney U test was used for group comparison. Repeated measures test was applied for data recorded at three time points. Results: A significant elevation in white blood cell (WBC) count was observed in COVID-positive intervention (p < 0.001) and control groups (p = 0.003), indicating no role of intervention on change in WBC number. WBC count (p = 0.002) and D-dimer (p = 0.002) significantly decreased in the COVID-recovered intervention group. D-dimer was also reduced in HCWs practicing Yogic breathing as compared to controls (p = 0.01). D-dimer was the primary outcome, which remained below 0.50 µg/ml (a cutoff value to define severity) in the COVID-positive yoga group (CYG) and decreased in the COVID-recovered yoga group (RYG) and the HCW yoga group (HYG) after intervention. A 6-min walk test (6MWT) showed an increase in distance covered among the COVID-positive patients (p = 0.01) and HCWs (p = 0.002) after intervention. The high-frequency power (p = 0.01) was found to be reduced in the COVID-positive intervention group. No significant change in neuropsychological parameters was observed. Conclusion: Yogic breathing lowered D-dimer, which is helpful in reducing thrombosis and venous thromboembolism in patients with COVID-19 besides lowering the chances of vaccine-induced thrombotic thrombocytopenia in vaccinated individuals. The breathing intervention improved exercise capacity in mild to moderate cases of COVID-19. Further studies can show if such breathing techniques can influence immunity-related genes, as reported recently in a study. We suggest that Yogic breathing may be considered an integrative approach for the management of patients with COVID. Trial registration: http://ctri.nic.in/Clinicaltrials/login.php, identifier: CTRI/2020/10/028195.

Amyotrophic Lateral Sclerosis (ALS) prediction model derived from plasma and CSF biomarkers.

Amyotrophic Lateral Sclerosis (ALS) is a degenerative disorder of motor neurons which leads to complete loss of movement in patients. The only FDA approved drug Riluzole provides only symptomatic relief to patients. Early Diagnosis of the disease warrants the importance of diagnostic and prognostic models for predicting disease and disease progression respectively. In the present study we represent the predictive statistical model for ALS using plasma and CSF biomarkers. Forward stepwise (Binary likelihood) Logistic regression model is developed for prediction of ALS. The model has been shown to have excellent validity (94%) with good sensitivity (98%) and specificity (93%). The area under the ROC curve is 99.3%. Along with age and BMI, VEGF (Vascular Endothelial Growth Factor), VEGFR2 (Vascular Endothelial Growth Factor Receptor 2) and TDP43 (TAR DNA Binding Protein 43) in CSF and VEGFR2 and OPTN (Optineurin) in plasma are good predictors of ALS.

Serum Levels of ARMS2, COL8A1, RAD51B, and VEGF and their Correlations in Age-related Macular Degeneration.

BACKGROUND: Many factors including genetic and environmental are responsible for the incidence of Age-related Macular Degeneration (AMD). However, its pathogenesis has not been clearly elucidated yet. OBJECTIVE: This study aimed to estimate the Age-Related Maculopathy Susceptibility 2 (ARMS2), Collagen type VIII Alpha 1 chain (COL8A1), Rad 51 paralog(RAD51B), and Vascular Endothelial Growth Factor (VEGF) protein levels in serum of AMD and control participants and to further investigate their correlation to understand AMD pathogenesis. METHODS: For this case-control study, 31 healthy control and 57 AMD patients were recruited from Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India. A blood sample was taken and serum was isolated from it. ELISA (enzyme-linked immunosorbent assay) was used for the estimation of proteins in the serum of patients. RESULTS: ARMS2 and COL8A1 levels were significantly elevated in the AMD group than in the control group. The highest levels of ARMS2, COL8A1, and VEGF proteins were recorded for the wet AMD sub-group. The study results endorsed significant positive correlation between these following molecules; ARMS2 and COL8A1 (r = 0.933, p < 0.0001), ARMS2 and RAD51B (r = 0.704, p < 0.0001), ARMS2 and VEGF (r = 0.925, p < 0.0001), COL8A1 and RAD51B (r = 0.736, p < 0.0001), COL8A1 and VEGF (r = 0.879, p < 0.0001), and RAD51B and VEGF (r = 0.691, p < 0.0001). CONCLUSION: The ARMS2 and COL8A1 levels were significantly higher and RAD51B was significantly lower in the AMD group than controls. Also, a significant statistical correlation was detected between these molecules, indicating that their interaction may be involved in the pathogenesis of AMD.

Can Yogic Breathing Techniques Like Simha Kriya and Isha Kriya Regulate COVID-19-Related Stress?

The global impact of Coronavirus Disease 2019 (COVID-19) is tremendous on human life, not only affecting the physical and mental health of population but also impacting the economic system of countries and individual itself. The present situation demands prompt response toward COVID-19 by equipping the humans with strategies to overcome the infection and stress associated with it. These strategies must not only be limited to preventive and therapeutic measures, but also aim at improving immunity and mental health. This can be achieved by yogic breathing techniques. In this perspective, we emphasize the importance of yogic breathing, Simha Kriya and Isha kriya, the simple yet effective breathing techniques.

Yoga Practice Is Beneficial for Maintaining Healthy Lifestyle and Endurance Under Restrictions and Stress Imposed by Lockdown During COVID-19 Pandemic.

Uncertainty about Coronavirus disease 2019 (COVID-19) and resulting lockdown caused widespread panic, stress, and anxiety. Yoga is a known practice that reduces stress and anxiety and may enhance immunity. This study aimed to (1) investigate that including Yoga in daily routine is beneficial for physical and mental health, and (2) to evaluate lifestyle of Yoga practitioners that may be instrumental in coping with stress associated with lockdown. This is a pan-India cross-sectional survey study, which was conducted during the lockdown. A self-rated scale, COVID Health Assessment Scale (CHAS), was designed by 11 experts in 3 Delphi rounds (Content valid ratio = 0.85) to evaluate the physical health, mental health, lifestyle, and coping skills of the individuals. The survey was made available digitally using Google forms and collected 23,760 CHAS responses. There were 23,290 valid responses (98%). After the study's inclusion and exclusion criteria of yogic practices, the respondents were categorized into the Yoga (n = 9,840) and Non-Yoga (n = 3,377) groups, who actively practiced Yoga during the lockdown in India. The statistical analyses were performed running logistic and multinomial regression and calculating odds ratio estimation using R software version 4.0.0. The non-Yoga group was more likely to use substances and unhealthy food and less likely to have good quality sleep. Yoga practitioners reported good physical ability and endurance. Yoga group also showed less anxiety, stress, fear, and having better coping strategies than the non-Yoga group. The Yoga group displayed striking and superior ability to cope with stress and anxiety associated with lockdown and COVID-19. In the Yoga group, participants performing meditation reportedly had relatively better mental health. Yoga may lead to risk reduction of COVID-19 by decreasing stress and improving immunity if specific yoga protocols are implemented through a global public health initiative.

Integrative Approach to COVID-19: An Indian Facebook Recipe for Mental Health.

Background: The COVID-19 pandemic has given the world a big blow and has forced the entire world to develop a new thought process. To cope with the stress of lockdown, it was important for people to indulge in educational and health activities to save them from the threats being caused by the news and social media. Summary: A Facebook page named Yoga scholars Post Graduate Institute of Medical Education and Research (PGIMER) was created where three sessions were held per day for 225 days regularly. This activity resulted in people adopting an integrative approach towards alternative medicine. Key message: This also made possible a trial of Ashwagandha for COVID-19 treatment by the Ayurveda, Yoga, Naturopathy, Unani, Siddha and Homeopathy (AYUSH) ministry.

Elevated Vasodilatory Cyclases and Shorter Telomere Length Contribute to High-Altitude Pulmonary Edema.

Rain, Manjari, Himanshi Chaudhary, Ritushree Kukreti, Tashi Thinlas, Ghulam Mohammad, and Qadar Pasha. Elevated vasodilatory cyclases and shorter telomere length contribute to high-altitude pulmonary edema. High Alt Med Biol. 19:60-68, 2018. AIM: High-altitude (HA) genetics is complex with respect to health and disease (HA pulmonary edema i.e., HAPE). Based on the widely recognized fact that oxidative stress is a major trigger of several physiological processes, this study was designed to establish the significance of vasodilatory cyclases and telomere length in HA physiology. The study was performed in three groups, namely HAPE-free sojourners (HAPE-f, n = 150), HAPE patients (HAPE-p, n = 150), and healthy highland natives or highlanders (HLs, n = 150). Variations in soluble guanylyl cyclase ß1-subunit (GUCY1B3) and adenylyl cyclase type 6 (ADCY6) were genotyped by the SNaPshot method and/or Fluidigm SNP type genotyping. Plasma GUCY1B3 and ADCY6 levels were estimated using ELISA, and relative telomere length was estimated by qRT-PCR. RESULTS: The rs7638AA genotype was over-represented in HLs compared with HAPE-f and HAPE-p (p = 0.035 and p = 0.012, respectively). Similarly, the rs7638A allele was prevalent in HLs compared with both groups, but significance was attained against HAPE-p (p = 0.012). Significantly elevated plasma levels of GUCY1B3 and ADCY6 were obtained in HAPE-p compared with HAPE-f (p = 0.001 and p = 0.006, respectively) and HLs (p = 3.31E-05 and p = 0.05, respectively). Shorter telomere length was observed in HAPE-p compared with HAPE-f (p > 0.05) and HLs (p = 0.017). CONCLUSION: Elevated cyclases and shorter telomere length associate with HAPE pathophysiology.

Role of ApoE gene polymorphism and nonconventional biochemical risk factors among very young individuals (aged less than 35 years) presenting with acute myocardial infarction.

BACKGROUND: Incidence rate of acute myocardial infarction (MI) has increased in younger population over the years. The young patients have a different risk profile, presentation, and prognosis than the elderly. Hence, it is essential to understand the risk factors in young patients for proper treatment. METHODS: Apolipoprotein E (ApoE) polymorphism and biochemicals such as total cholesterol, serum triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein(a), insulin, interleukin-6, homocysteine, fibrinogen, and highly sensitive C-reactive protein were investigated in very young MI (yMI patients; age ≤ 35 years; n = 125), in old MI (oMI patients; age >35 and < 80 years; n = 111), and healthy controls (age ≤35 years; n = 103). RESULTS: HDL-C was significantly lower in yMI patients than in controls (p = 2.63E-04) and oMI patients (p = 1.29E-05). ApoA1 was also lowest in yMI patients, but significant only in comparison to controls (p = 2.62E.04). The yMI group had the highest ratios of total cholesterol:HDL-C (p = 0.027 in yMI patients versus controls and p = 0.018 in yMI patients versus oMI patients), LDL-C:HDL-C (p = 0.002 in yMI patients versus controls and p = 0.005 in yMI patients versus oMI patients), and ApoB:ApoA1 (p = 8.75E-05 in yMI patients versus controls and p > 0.05 in yMI patients versus oMI patients). No significant pattern of ApoE polymorphisms was observed. CONCLUSION: The lower level of HDL-C and ApoA1 and higher ratios of total cholesterol:HDL-C, LDL-C:HDL-C, and ApoB:ApoA1 are risk factors for MI in young patients.

Biochemical and genetic role of apelin in essential hypertension and acute coronary syndrome.

BACKGROUND: Apelin-APJ pathway has emerged as a potent regulator of blood pressure (BP) and blood flow in vasculature and heart. Variants in apelin gene may affect the vascular tone in peripheral circulation or heart, thereby predisposing to cardiovascular diseases. The aim of our study was to investigate the association of two apelin gene polymorphisms rs3761581 and rs2235312, and apelin levels in patients with essential hypertension (EH) and acute coronary syndrome (ACS). METHODS: The study comprised of three groups namely, (1) 118 healthy control subjects, (2) 92 EH patients, and (3) 60 ACS patients. DNA was extracted from peripheral blood leukocytes and genotyping was performed by SNaPshot method. Plasma apelin 13 levels were estimated using ELISA. RESULTS: EH and ACS patients had a significantly lower level of apelin 13, regardless of gender (p=0.003, p=0.017, respectively). Interestingly, the female EH and ACS patients had lower levels of apelin 13 than their male counterparts. The G allele of rs3761581 was more apparent in patients especially in ACS than the controls. CONCLUSION: Reduced apelin levels may enhance vasoconstriction to influence high BP and heart's workload in EH and ACS. Genetic involvement of apelin needs to be established in well-defined larger sample size.

Association between the Glu298Asp and 4b/4a polymorphisms of endothelial nitric oxide synthase and coronary slow flow in the North Indian population.

RATIONALE: Genetic variants in endothelial nitric oxide synthase gene (NOS3) leading to endothelial dysfunction may be predispose to the coronary slow-flow phenomenon (CSFP). METHODS AND RESULTS: In this study, we examined the relationship between Glu298Asp (894G/T) and 4b/4a polymorphisms of NOS3 and CSFP. A total of 27 patients with CSFP but otherwise normal coronary arteries (mean age 50.4±8.2 years) and 200 controls with a normal coronary angiogram (mean age 53.1±8.6 years) were screened for Glu298Asp and 4b/4a polymorphisms by restriction fragment length polymorphism and PCR, respectively. Nitric oxide levels were determined using Griess' enzymatic method for an association with the polymorphisms. The genotype distribution of the Glu298Asp polymorphism differed significantly between the CSFP patients and controls (P=0.004). The dominant genetic model showed that GT+TT was significantly prevalent in patients in comparison with controls (P=0.014) and the T allele was significantly prevalent in patients (P=0.002). The genetic distribution of 4b/4a differed significantly for the heterozygous genotype ba (P=0.047). The overdominant genetic model re-established that the ba genotype was significantly prevalent in patients (P=0.044). Nitric oxide level was higher in patients than in controls, the values being 144.51±43.25 and 129.64±29.47 µmol/l, respectively (P>0.05). The genotypes of Glu298Asp showed a trend of association with nitric oxide levels, which decreased linearly in the order of GG, GT, and TT (P>0.05). CONCLUSION: The Glu298Asp polymorphism of NOS3 associates with CSFP.

ß-T594M epithelial sodium channel gene polymorphism and essential hypertension in individuals of Indo-Aryan ancestry in Northern India.

BACKGROUND: The T594M variant of the ß-subunit of the sodium epithelial channel (ENaC) gene may contribute to hypertension in individuals of Indo-Aryan origin. METHODS: Present study was performed to assess the role of the ENaC gene variant as an independent risk factor for hypertension in subjects of Indo-Aryan ancestry. A total of 150 patients of recently detected essential hypertension and 150 matched controls were genotyped for the T594M polymorphism of the ENaC gene by PCR-RFLP method. RESULTS: ß-T594M mutation was found to be non-polymorphic. There was major genotype call in both the groups i.e. cases and controls. Other phenotypic parameters like age, sex and body mass index were also similar among hypertensive patients and controls (P > 0.05). Hypertensive patients had significantly higher total cholesterol and triglycerides compared with controls (P < 0.0001). CONCLUSION: These results do not suggest an important role for the T594M variant of the ENaC gene contributing to either the development or severity of hypertension in subjects of Indo-Aryan ancestry.