Cancer risk and male Infertility: Unravelling predictive biomarkers and prognostic indicators.

In recent years, there has been a global increase in cases of male infertility. There are about 30 million cases of male infertility worldwide and male reproductive health is showing rapid decline in last few decades. It is now recognized as a potential risk factor for developing certain types of cancer, particularly genitourinary malignancies like testicular and prostate cancer. Male infertility is considered a potential indicator of overall health and an early biomarker for cancer. Cases of unexplained male factor infertility have high levels of oxidative stress and oxidative DNA damage and this induces both denovo germ line mutations and epimutations due to build up of 8-hydroxy 2 deoxygunaosine abase which is highly mutagenic and also induces hypomethylation and genomic instability. Consequently, there is growing evidence to explore the various factors contributing to an increased cancer risk. Currently, the available prognostic and predictive biomarkers associated with semen characteristics and cancer risk are limited but gaining significant attention in clinical research for the diagnosis and treatment of elevated cancer risk in the individual and in offspring. The male germ cell being transcriptionally and translationally inert has a highly truncated repair mechanism and has minimal antioxidants and thus most vulnerable to oxidative injury due to environmental factors and unhealthy lifestyle and social habits. Therefore, advancing our understanding requires a thorough evaluation of the pathophysiologic mechanisms at the DNA, RNA, protein, and metabolite levels to identify key biomarkers that may underlie the pathogenesis of male infertility and associated cancer. Advanced methodologies such as genomics, epigenetics, proteomics, transcriptomics, and metabolomics stand at the forefront of cutting-edge approaches for discovering novel biomarkers, spanning from infertility to associated cancer types. Henceforth, in this review, we aim to assess the role and potential of recently identified predictive and prognostic biomarkers, offering insights into the success of assisted reproductive technologies, causes of azoospermia and idiopathic infertility, the impact of integrated holistic approach and lifestyle modifications, and the monitoring of cancer susceptibility, initiation and progression. Comprehending these biomarkers is crucial for providing comprehensive counselling to infertile men and cancer patients, along with their families.

Beyond the optic nerve: Genetics, diagnosis, and promising therapies for glaucoma.

Glaucoma stands as a leading global cause of blindness, affecting millions. It entails optic nerve damage and vision loss, categorized into open-angle and closed-angle glaucoma with subtypes like POAG, ACG, XFG, PCG, PDG, and developmental glaucoma. The pathophysiological and genetic factors behind glaucoma remain partially understood, with past studies linking intraocular pressure (IOP) levels to retinal ganglion cell death. Open-angle glaucoma involves elevated resistance to aqueous outflow via the trabecular meshwork, while angle-closure glaucoma typically sees drainage pathways obstructed by the iris. Genes have been identified for POAG, ACG, XFG, PCG, PDG, and developmental glaucoma, allowing for early-onset detection and the emergence of gene therapy as an effective treatment. Nevertheless, diagnostic and treatment options have their constraints, necessitating large-scale, well-designed studies to deepen our grasp of genetics' role in glaucoma's pathogenesis. This review delves into glaucoma's risk factors, pathophysiology, genetics, diagnosis, and available treatment options, including gene therapy. Additionally, it suggests alternative therapies like yoga and meditation as adjunct treatments for glaucoma prevention. Overall, this review advances our comprehension of the pathophysiology and genetic associations of glaucoma while highlighting the potential of gene therapy as a treatment avenue. Further research is imperative to fully elucidate the genetic mechanisms underpinning glaucoma and to devise effective treatments.

Yoga maintains Th17/Treg cell homeostasis and reduces the rate of T cell aging in rheumatoid arthritis: a randomized controlled trial.

The pathogenesis of rheumatoid arthritis (RA) is characterized by a Th17/Treg cell imbalance. A pro-inflammatory cytokine milieu that promotes the continued proliferation of Th17 cells is related to the development of autoinflammation. In RA, T cells have several hallmarks of cellular aging, and they accumulate DNA damage, predisposing to the occurrence of mutations and epigenetic alterations. Since the onset, progression, and treatment response are influenced by a variety of external stressors and environmental factors, this study aimed to evaluate the impact of 8-week yoga practice on disease severity, T cell subsets, markers of T cell ageing and inflammation, epigenetic alterations and gene expression patterns in active RA patients on standard disease-modifying anti-rheumatic drugs (DMARDs). A total of 64 participants with active RA were randomized into 2 groups, yoga group (n = 32) or non-yoga group (n = 32); that were assessed for disease severity, at baseline and after 8 week duration, for Disease Activity Score (DAS28-ESR), T cell subsets [Th17 (CD3+ CD4+ IL17+ RORγt+) cells and Treg (CD3+ CD4+ CD25+ CD127-Foxp3+) cells], markers of T cell aging [aged Th17 cells (CD3+ CD4+ IL17+ RORγt+ CD28-) and aged Treg cells (CD3+ CD4+ CD25+ CD127-Foxp3+ CD28-)], pro-inflammatory markers [IL-6, and IL-17], anti-inflammatory markers [TGF-ß, and IL-10], epigenetic alterations [5-methyl cytosine, 5-hydroxymethyl cytosine, and HDAC1] and gene expression patterns [RORγt, FoxP3, IL-17, IL-6, TGF-ß, CXCL2, CXCR2, and JUN]. In yoga group, there was a significant improvement in DAS28-ESR scores at the end of 8-weeks of yoga program. The Th17 cells and aged T cell subsets showed a significant decline whereas Treg cell population showed a significant elevation in yoga group. There were significant improvements observed in epigenetic markers as well as inflammatory markers post 8-weeks of yoga practice. The yoga group showed downregulation of RORγt, IL-17, IL-6, CXCL2, CXCR2, and upregulation of FoxP3 and TGF-ß transcripts. Yoga enables the maintenance of immune-homeostasis as evident by increased Treg cell population and reduced Th17 cell population. Yoga reduces the rate of immunological aging in T cells, as seen by the reduction in population of aged Th17 cells and aged Treg cells. Yoga positively modifies transcriptome and epigenome by normalization of various inflammatory markers, gene expression patterns and epigenetic alterations. Taken together, yoga reduces RA severity, and aids in immune-modulation and hence can be beneficial as an adjunct therapy.

From Inner Balance to Visual Health: Unraveling the Therapeutic Role of Yoga in Optic Neuropathy and Ocular Manifestations - Narrative Review.

The optic nerve comprises approximately 1.2 million axons of retinal ganglion cells and is vulnerable to degeneration due to a myriad of causes. While traditional treatments have been the cornerstone of ocular care, emerging evidence highlights the benefits of integrative approaches, which can be used as an adjunct in the management of optic neuropathy. Yoga is a mind-body energy medicine encompasses physical postures, breath control, and meditation. Currently, it has gained attention for its holistic effects on well-being, by promoting health, preventing onset of diseases, adjunct in disease management, and for its rehabilitative potential. In addition, the underlying mechanisms through which yoga exerts its therapeutic influence, evaluates clinical outcomes, and explores potential synergistic effects with conventional treatments remain largely unexplored. Neuroprotective mechanisms of yoga, such as enhancing retinal ganglion cell function, reducing oxidative stress, coupled with its ability to modulate inflammatory processes and improve circulation, contribute to its potential benefits in visual health. Analysis of clinical studies reveals promising outcomes, including improvements in visual acuity, visual fields, quality of life, and functional outcomes in individuals with optic neuropathy and ocular manifestations who undergo yoga intervention (especially dhyaan) with awareness of breath. Furthermore, the integration of yoga with conventional treatments and complementary modalities unveils the possibilities of multidisciplinary approaches in ocular care that need evaluation. By unraveling the role of yoga intervention in ocular health, this review provides valuable insights for clinicians and researchers, fostering a deeper understanding of the mind-body connection and paving the way for enhanced visual health outcomes. Embracing yoga as an adjunctive therapy may has the potential to revolutionize the management of optic neuropathy and ocular manifestations, offering individuals a holistic approach to optimize visual well-being, reduce comorbid depression and caregiver burden, and improve overall quality of life.

HLA-G 3'UTR polymorphisms & response to a yoga-based lifestyle intervention in rheumatoid arthritis: A randomized controlled trial.

Background & objectives: Human leucocyte antigen (HLA)-G plays a vital role in immunomodulation in rheumatoid arthritis (RA). The mounting evidence suggests a link between HLA-G gene polymorphisms, disease susceptibility and methotrexate treatment response. Various environmental factors influence the onset and progression of RA and its treatment outcomes. The aim is to identify the treatment response of HLA-G 3' untranslated region polymorphisms to yoga-based lifestyle intervention (YBLI). Methods: In this eight-week single-blinded randomized controlled trial (CTRI/2017/05/008589), patients with RA (n=140) were randomized into two groups namely, yoga group or non-yoga group. Baseline genomic DNA was isolated using salting-out method. PCR-based methods were used for genotyping. The levels of soluble (s) HLA-G and disease activity were assessed by ELISA and disease activity score-28-erythrocyte sedimentation rate (DAS28-ESR), respectively, at baseline (day 0) and after eight weeks of intervention. Results: Low-producing sHLA-G genotypes, i.e. +3142GG and 14 bp ins/ins, showed a significant increase in sHLA-G levels after YBLI. The association analysis between HLA-G polymorphisms and treatment for RA showed no considerable differential treatment remission in either of the groups (P>0.05). The percentages of improvement were higher in the yoga group as compared to the non-yoga group in both the HLA-G +3142G>C and 14 bp ins/del polymorphisms irrespective of their respective genotypes. No significant association was found between sHLA-G levels and disease activity with respect to genotypes. Interpretation & conclusions: Yoga intervention results in improvement and reduced severity of RA in patients irrespective of the HLA-G 14 bp ins/del or +3142G>C polymorphisms. YBLI may be used as an adjunct therapy in RA independent of the genotypes.

Transcriptional modulation of inflammation, and aging in Indian obese adults following a 12-week yoga-based lifestyle intervention: A randomized controlled trial.

Introduction: Obesity is one of the major global problems in today's world, both in children, and the adult age group. Current evidence suggests obesity alters the expression of various genes related to oxidative stress, inflammation, and aging. In recent times complementary therapy like yoga-based lifestyle intervention (YBLI) is used as an adjunct therapy to modern medicine. This study examines the efficacy of 12 weeks of yoga-based lifestyle intervention with standard care (SC) on the expression of genes related to oxidative stress, inflammation, and aging in obese adults. Methods: This was a two-arm parallel randomized control trial implemented at Integral Health Clinic (IHC), an outpatient facility that regularly conducted YBLI programs for the prevention of lifestyle diseases like obesity and diabetes in the Department of Physiology, All India Institute of Medical Sciences (AIIMS), New Delhi. Blood samples at baseline and weeks 2,4, and 12 were collected from 72 adults (male n = 21; female n = 51) of age 20-45 years with a body-mass index (BMI) of 25-35 kg/m2 who were randomized to receive either a 12-week SC (n = 36) or YBLI (n = 36). SC included recommendations for the management of obesity as per Indian guidelines including a low-calorie individualized diet and physical activity. Asana (physical postures), pranayama (breathing exercises), and meditation were all part of the YBLI. Primary outcomes were relative fold change in the expression of genes associated with oxidative stress [Nuclear factor-kappa B (NF-Kappa B)], inflammation [Tumor necrosis factor-α (TNFα), interleukin-6 (IL-6)], and aging [human telomerase reverse transcriptase (TERT)] in peripheral blood mononuclear cells between the two groups at week-12. Results: There were no significant changes in fold change of TERT, IL-6, and NF-kappa B between the groups at week 12. The relative fold change of TERT was significantly greater in the YBLI group (p = <0.0001) vs the SC group at 2 weeks. The relative fold change of TNF α was significantly lower at week 12 in YBLI though the change was not continuous and reliable. Within both groups, TERT expression was significantly increased at week 2 though the change was greater in the YBLI group (p < 0.0001). TNF α gene expression was significantly lower at weeks 2 and 4, compared to baseline level, in the SC group but it increased at week 12. Conclusion: The results while did not confirm our hypothesis, are important to share with the scientific society, to be able to improve prospective study designs and find optimal time/intervention/biological marker settings for this highly important scientific field. The results are suggestive of a positive impact of YBLI and SC on the fold change of aging-related TERT gene in obesity, though the benefit was not evident till week 12. However, the results should be evaluated with caution and in light of other published studies. To better understand the positive effects of YBLI on oxidative stress, inflammation, and aging-related gene expression in obesity, larger studies are recommended.

Potential Role of Yoga Intervention in the Management of Chronic Non-malignant Pain.

Pain is an unpleasant and upsetting experience. Persistent pain has an impact on an individual's quality of life which causes stress and mood disorders. There are currently no pain-relieving techniques available that can eliminate pain and offer relief without causing any adverse effects. These factors draw attention to traditional treatments like yoga and meditation, which can reduce biological stress and hence increase immunity, as well as alleviate the psychological and emotional suffering produced by pain. Yoga reduces the stress response and the pain cascade via the downregulation of the hypothalamus-pituitary-adrenal (HPA) axis and vagal stimulation. Yoga is a cost-effective growing health practice that, unlike pharmaceuticals, has no side effects and can help patients stay in remission for longer periods of time with fewer relapses. Yoga not only reduces stress and depression severity but also improves functional status and reduces pain perception. This article highlights the impact of yoga on pain management and on a malfunctioning immune system, which leads to improved health, pain reduction, disease management, and improvement in overall quality of life.

A 12-Week Yoga-Based Lifestyle Intervention Might Positively Modify Cellular Aging in Indian Obese Individuals: A Randomized-Controlled Trial.

Background: Telomeres and telomerase are considered cardinal biomarkers of cellular aging. Shorter telomeres and low telomerase activity have been associated with obesity and accelerated aging. Objective: To compare the effects of a yoga-based lifestyle intervention (YBLI) with the standard of care (SOC) on cellular aging by estimating telomere length (TL) and telomerase activity in obesity. Design and setting: A parallel, two-arm, randomized-controlled trial was conducted at the Integral Health Clinic, Department of Physiology, All India Institute of Medical Sciences, New Delhi, from March 2017 to October 2019. Participants: Obese (n = 72), body mass index (BMI), 25-35 kg/m2, aged 20-45 years, male (21), and female (51). Intervention: Seventy-two obese participants were randomized to receive either a 12-week SOC (n = 36) or YBLI (n = 36). SOC included management of obesity as per Indian guidelines including a hypocaloric individualized diet and physical activity. The pretested YBLI included asana (physical postures), pranayama (breathing exercises), and meditation. Methods: Blood samples were collected from both the groups at baseline, 2, 4, and 12 weeks. DNA was extracted from peripheral blood mononuclear cells. TL was measured by quantitative PCR, and serum telomerase levels by immunoassay. Outcome measures: Primary outcome measures were the changes in the TL and telomerase levels between the two groups at week 12. Secondary outcome measures were the changes in TL and telomerase, and anthropometric parameters (body weight, BMI, waist-to-hip ratio) at 2, 4, and 12 weeks of intervention in both SOC and YBLI groups. Results: There were no significant changes in TL and telomerase levels between the groups at week 12. The TL was significantly greater in the YBLI group versus the SOC group (p < 0.0001) at 2 weeks. The anthropometric and physiological parameters were influenced positively by both SOC and YBLI. Conclusion: The study did not meet the primary objective, although the results are suggestive of a positive impact of YBLI on aging in obesity as noted within the YBLI group. However, the results should be interpreted carefully, and in the light of other published data. Larger studies to better understand the possible positive benefits of YBLI on cellular aging are recommended. Clinical Trail Registration No. CTRI/2016/08/007136.

Yoga in major depressive disorder: molecular mechanisms and clinical utility.

Major depressive disorder (MDD) is a mind-body disorder. Cellular aging has been implicated in the pathogenesis of MDD with the altered mind-body communication markers like stress response, immune response, nutrition sensing, and a range of other regulatory feedback systems. In this age of super specializations, one specific target and interventions (preferably a drug) on it are being rigorously sought by the health care community and industry, but have failed in it in the last fifty years in spite of advances in technology. Since, depression is a complex disorder associated with increased incidence of other complex disorders, it must be treated by an integrated holistic approach that can address the complexity of MDD. Interventions targeting accelerated biological aging to increase cellular health in whole body have potential to manage complex conditions like MDD and its overlapping symptoms and comorbidities. Yoga has the potential to be the nexus between, clinical management of MDD and other lifestyle diseases.

Yoga improves mitochondrial health and reduces severity of autoimmune inflammatory arthritis: A randomized controlled trial.

BACKGROUND: Oxidative stress (OS) and mitochondrial alterations have been implicated in the pathogenesis of rheumatoid arthritis (RA). Various environmental triggers like air pollutants, smoking, unhealthy social habits and sedentary lifestyle induce OS, which may compromise mitochondrial integrity. This trial was designed to explore the effect of 8-weeks yoga practice on mitochondrial health and disease severity in an active RA group compared with a usual-care control group. METHODS: A total of 70 subjects were randomized into two groups: yoga group and non-yoga group. Mitochondrial health was assessed by calculation of mitochondrial DNA copy number (mtDNA-CN), OS markers, mitochondrial activity, mitochondrial membrane potential (ΔΨm), circadian rhythm markers and transcripts associated with mitochondrial integrity: AMPK, TIMP-1, KLOTHO, SIRT-1, and TFAM. Parameters of disease activity and disability quotient were also assessed by disease activity score - erythrocyte sedimentation rate (DAS28-ESR) and health assessment questionnaire-disability index (HAQ-DI), respectively. RESULTS: In yoga group, there was a significant upregulation of mtDNA-CN, mitochondrial activity markers, ΔΨm, and transcripts that maintain mitochondrial integrity after 8-weeks of yoga. There was optimization of OS markers, and circadian rhythm markers post 8-weeks practice of yoga. Yoga group participants showed significant improvements in DAS28-ESR (p < 0.05) and HAQ-DI (p < 0.05) over the non-yoga group. CONCLUSION: Adoption of yoga by RA patients holds the key to enhance mitochondrial health, improve circadian rhythm markers, OS marker regulation, upregulation of transcripts that maintain mitochondrial integrity, reduce disease activity and its associated consequences on health outcome and hence can be beneficial as an adjunct therapy.

Effect of Mindfulness Meditation on Intraocular Pressure and Trabecular Meshwork Gene Expression: A Randomized Controlled Trial.

PURPOSE: To evaluate the effect of mindfulness meditation (MM) on intraocular pressure (IOP) and trabecular meshwork (TM) gene expression in patients with medically uncontrolled primary open angle glaucoma (POAG). DESIGN: Parallel arm, single-masked, randomized controlled trial. METHODS: Sixty POAG patients with IOP ≥21 mm Hg taking maximal topical medication and scheduled for trabeculectomy were included in this study at a tertiary eye care center in India. Thirty patients (Group 1) underwent 3 weeks of 45-minute daily MM sessions in addition to medical therapy while Group 2 continued medical therapy only. Primary outcome was change in IOP (ΔIOP) after 3 weeks of MM. Secondary outcomes were probability of success, percentage of reduction in IOP, effect on diurnal variations of IOP, changes in quality of life (QoL), and changes in gene expression patterns in TM. RESULTS: At 3 weeks, a significant decrease in IOP was seen in Group 1 (20.16 ± 3.3 to 15.05 ± 2.4mm Hg; P = .001), compared to Group 2 (21.2 ± 5.6 to 20.0 ± 5.8mm Hg; P = .38). ΔIOP was significantly higher in Group 1 than in Group 2 (5.0 ± 1.80 vs. 0.20 ± 3.03mm Hg; P = .001). Analysis of gene expression revealed significant upregulation of nitric oxide synthetase (NOS1 and NOS3) and neuroprotective genes with downregulation of proinflammatory genes in Group 1 in comparison to Group 2 (P = .001). CONCLUSIONS: MM was associated with significant decrease in IOP and changes in TM gene expression, indicating its direct impact on ocular tissues.

Yoga and its impact on chronic inflammatory autoimmune arthritis.

Rheumatoid arthritis (RA) is one of the most common chronic inflammatory autoimmune diseases, which adversely affects the quality of life. RA is a disease of unknown etiology, however, both genetic and environmental factors appear to contribute to the susceptibility to this disease. The severity and progression of the disease are attributable to the release of a host of inflammatory cytokines, cytotoxic and immune regulatory factors. The treatments of RA are primarily limited to symptomatic alleviation of pain or other symptoms or to the use of cytotoxic drug treatment in severe forms of the disease which is commonly associated with significant side effects. Despite lack of a cure, the disease may be controlled by mind-body interventions. Holistic treatments such as Yoga significantly improve and reduce the psycho-somatic symptoms, pain perception, disability quotient, joint flexibility, range of motion, posture, muscle strength, coordination, and disease activity. Here, we discuss the features of RA and address how Yoga can be used as a therapeutic regimen to improve the quality of life of patients with RA.

Effect of an 8-Week Yoga-Based Lifestyle Intervention on Psycho-Neuro-Immune Axis, Disease Activity, and Perceived Quality of Life in Rheumatoid Arthritis Patients: A Randomized Controlled Trial.

Various external stressors and environmental challenges lead to the provocation of the immune system in autoimmune diseases like Rheumatoid arthritis (RA). The inappropriate immune response further triggers the cascade of inflammatory changes resulting in precipitation of symptoms and hampers quality of life (QOL). The underlying psycho-somatic component of the disease requires a holistic approach to its treatment dimension rather than the use of pharmacotherapy. The applicability of mind-body interventions has become essential in today's fast-paced life. Yoga, a mind-body technique, alters the mind's capacity to facilitate systemic functioning at multiple organ system levels. Hence, we conducted this study to evaluate the impact of 8 weeks of a yoga-based lifestyle intervention (YBLI) on psycho-neuro-immune markers, gene expression patterns, and QOL in RA patients on routine medical therapy. A total of 66 patients were randomized into two groups: yoga group or non-yoga group and were assessed for a panel of inflammatory cytokines (IL-6, IL-17A, TNF-α, and TGF-ß), mind-body communicative markers (BDNF, DHEAS, ß-endorphin, and sirtuin) and transcript levels of various genes (IL-6, TNF-α, NFKB1, TGF-ß, and CTLA4). We assessed disease activity and QOL using the DAS28-ESR and WHOQOL-BREF questionnaire, respectively. Yoga group observed significant improvements in the levels of markers, which influenced the psycho-neuro-immune axis (p < 0.001) with an estimated effect size from small to medium range. In the yoga group, there was a significant reduction in DAS28-ESR (p < 0.001) and improvement seen in the physical health, psychological, social relationships domains (p < 0.001) of QOL, except environmental (p > 0.05). The yoga group showed downregulation of IL-6, TNF-α, and CTLA4 and upregulation of TGF-ß. These results suggest that a decrease in disease activity after yoga practice is associated with a significant reduction in inflammatory cytokines, the elevation of mind-body communicative markers, and normalization of various transcript levels, which improved QOL. Thus the adoption of YBLI improves clinical outcome in RA, and decreases systemic inflammation by its beneficial effects on psycho-neuro-immune axis and normalization of dysregulated transcripts. Thus YBLI may be used for RA patients as an adjunctive therapy.

Sperm methylome alterations following yoga-based lifestyle intervention in patients of primary male infertility: A pilot study.

A majority of the cases of primary male infertility are idiopathic with the underlying molecular mechanisms contributing to the pathophysiology as yet unknown. Effects of the environment can alter the sperm epigenome thereby impacting male reproductive health. Epigenetic mechanisms are crucial to understanding health and disease, and methylome alterations are now known to have far-reaching clinical implications. Here, we report the results from our pilot study, a first of its kind analysis of the effect of the traditional practice of yoga on human sperm quality. We find marked improvement in sperm characteristics in patients of idiopathic male infertility following a supervised 21-day yoga regimen. Furthermore, next-generation sequencing-based methylome analysis reveals alterations in the sperm epigenome of these patients. We find that the practice of yoga is associated with DNA methylation changes at nearly 400 genes, 147 of which were hypermethylated while 229 were hypomethylated. These included promoters of several genes linked to maintenance of fertility and genomic integrity. This novel piece of work draws a direct link between positive lifestyle practices and male reproductive health.

Impact of yoga based mind-body intervention on systemic inflammatory markers and co-morbid depression in active Rheumatoid arthritis patients: A randomized controlled trial.

BACKGROUND: Recovery of patients with rheumatoid arthritis (RA) depends on several physical and psychological factors, besides pharmacological treatment. Co-morbid depression adversely affects the outcome in RA. Usual medical therapies have a limited scope and fail to cure the psychological component of the disease. With advanced therapeutic options, achieving a state of remission has become the treatment goal, yoga based mind body intervention (MBI) may provide a holistic approach in its treatment dimension. Hence, MBIs are the need of hour as majority of diseases have a psychosomatic component. OBJECTIVE: To explore the effect of Yoga based MBI on disease specific inflammatory markers and depression severity in active RA patients on routine disease modifying anti-rheumatic drugs (DMARDs) therapy. METHODS: A total of 72 RA patients were randomized into 2 groups: yoga group (yoga with DMARDs) and control group (DMARDs only). Blood samples were collected pre and post intervention for primary outcome measurements of systemic biomarkers. Disease activity score 28, erythrocyte sedimentation rate (DAS28ESR) and health assessment questionnaire disability index (HAQ-DI) were used to assess disease activity and functional status respectively at pre and post intervention time-points. Secondary outcome, depression severity, was assessed by Beck Depression Inventory II scale (BDI-II) at 2 weekly intervals during 8 weeks of the study interventional plan. RESULTS: After 8 weeks of yoga based MBI, there was significant decrease in the severity of RA as seen by reduction in levels of various systemic inflammatory markers as well as in DAS28ESR (p-value <0.0001; effect size = 0.210) and HAQ-DI (p-value 0.001; effect size = 0.159). Also, yoga group experienced a statistically significant time dependent step-wise decline in depression symptoms over the period of 8 weeks as compared to control group (p-value <0.0001; effect size = 0.5). Regression analysis showed greater reduction in the scores of BDI-II with DAS28ESR (R2 = 0.426; p <  0.0001) and HAQ-DI (R2 = 0.236; p = 0.003) in yoga group. CONCLUSIONS: Yoga, a mind body intervention re-established immunological tolerance by aiding remission at molecular and cellular level along with significant reduction in depression. Thus in this severe autoimmune inflammatory arthritis with a major psychosomatic component, yoga can be used as a complementary/adjunct therapy.

Impact of yoga based lifestyle intervention on psychological stress and quality of life in the parents of children with retinoblastoma.

BACKGROUND: Childhood cancers are associated with a psychological burden to the parents and hence, decline their mental and physical health and overall quality of life. PURPOSE: The purpose of the present study is to investigate the impact of 12-weeks yoga based lifestyle intervention on psychological stress and quality of life in the parents of children affected with retinoblastoma. METHOD: Single arm prospective clinical trial conducted from October 2015 to October 2017 at the Laboratory for Molecular Reproduction and Genetics, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India. A pre-tested 12-weeks yoga based lifestyle intervention included asanas (physical postures), pranayama (breathing exercises), dhyana (meditation), relaxation techniques, lectures and films on yoga, interactive sessions and individualized advice was administered to the participants. RESULTS: 12-weeks of yoga based lifestyle intervention programme leads to a significant improvement in psychological stress and overall quality of life in the parents of retinoblastoma patients. There was a significant improvement in all the domains (physical health, psychological health, social relationships, and environment) of WHOQOL-BREF from baseline (day 0) to 12-weeks of yoga based lifestyle intervention. Yoga based lifestyle intervention also led to a significant increase in the levels of brain derived neurotrophic factor, dehydroepiandrosterone sulphate, sirtuin 1 and decreased the cortisol and IL-6 levels. CONCLUSION: Yoga based lifestyle intervention reduced the severity of psychological stress and resulted in improvement in overall quality of life and upregulation in levels of systemic biomarkers of neuroplasticity. YBLI may serve as a beneficial therapy and may also act as an effective medium for better stress management to develop better coping strategies in the parents of retinoblastoma patients.

5-HTTLPR and MTHFR 677C>T polymorphisms and response to yoga-based lifestyle intervention in major depressive disorder: A randomized active-controlled trial.

BACKGROUND: There is growing evidence suggesting that both genetic and environmental factors modulate treatment outcome in, a highly heterogeneous, major depressive disorder (MDD). 5-HTTLPR variant of the serotonin transporter gene (SLC6A4) and MTHFR 677C>T polymorphisms have been linked to the pathogenesis of MDD, and antidepressant treatment response. The evidence is lacking on the clinical utility of yoga in patients with MDD who have 5-HTTLPR and MTHFR 677C>T polymorphisms and less likely to respond to medications (SSRIs). AIMS: We aimed to examine the impact of YBLI in those who have susceptible 5-HTTLPR and MTHFR 677C>T polymorphisms and are less likely to drug therapy with SSRIs. SETTINGS AND DESIGN: In a 12 week randomized active-controlled trial, MDD patients (n = 178) were randomized to receive YBLI or drug therapy. METHODS: Genotyping was conducted using PCR-based methods. The clinical remission was defined as BDI-II score ≤ 9. STATISTICAL ANALYSIS USED: An intent-to-treat analysis was performed, and the association of genotype with treatment remission consisted of the logistic regression model. A P value of <0.05 was considered statistically significant. RESULTS: Multivariate logistic regression models for remission including either 5-HTTLPR or MTHFR 677C>T genotypes showed statistically significant odds of remission in YOGA arm vs. DRUG arm. Neither 5-HTTLPR nor MTHFR 677C>T genotype showed any influence on remission to YBLI (P = 0.73 and P = 0.64, respectively). Further analysis showed childhood adversity interact with 5-HTTLPR and MTHFR 677C>T polymorphisms to decrease treatment response in DRUG treatment arm, but not in YOGA arm. CONCLUSIONS: YBLI provides MDD remission in those who have susceptible 5-HTTLPR and MTHFR 677C>T polymorphisms and are resistant to SSRIs treatment. YBLI may be therapeutic for MDD independent of heterogeneity in its etiopathogenesis.

Meditation enhances brain oxygenation, upregulates BDNF and improves quality of life in patients with primary open angle glaucoma: A randomized controlled trial.

BACKGROUND: Glaucoma (POAG) is a kind of neurodegenerative disease known to be closely associated with stress and adverse quality of life (QOL). Stress has also been shown to be involved in etiopathogenesis of primary open angle glaucoma (POAG). Complementary treatment in form of Meditation has been reported to improve QOL, brain oxygenation and decrease markers of stress. With this premise, a randomized controlled trial was carried out to assess the effect of Meditation on intraocular pressure, subjective QOL and objective markers of stress and brain oxygenation in patients with POAG. METHODS: Sixty patients were randomized into intervention and control groups. Intervention group underwent 45 minutes of Meditation daily for 6 weeks in addition to standard medical treatment while controls received only standard medical treatment. Inclusion criteria were patients with POAG, age >45 years, best corrected visual acuity >6/60. Patients with other ocular co-morbid conditions contributing to vision loss, systemic diseases, patients already practicing meditation in any form were excluded. An assessment of IOP, brain oxygenation using functional near infrared spectroscopy (fNIRS), QOL (WHO-BREF QOL) and stress markers in serum (cortisol, ß-endorphins, interleukin-6, brain derived neurotrophic factor (BDNF), reactive oxygen species) was made at baseline and at 6 weeks. RESULTS: 21 female and 39 male patients were enrolled with a mean age of 57.28±9.37 years. All parameters were comparable between two groups at baseline. At 6 weeks mean level of IOP decreased significantly in intervention group (15.9±1.8 mmHg to 14.4±1.21 mm Hg, p-value 0.0001) as compared to control group (15.7±1.4 mmHg to 15.65±1.41, p-value 0.41). fNIRS showed significant improvement in oxygenated hemoglobin change (ΔHbO) in intervention group in the prefrontal cortex (p-value <  0.0001) as compared to control group (p-value 0.52). WHO-BREF QOL score increased significantly in intervention group (86.6±6.16 to 93.3±5.66, p-value 0.0001) as compared to control (89±7.25 to 89.07±3.24, p-value 0.74).Mean serum cortisol decreased significantly in intervention group (497±46.37 ng/ml to 447±53.78 ng/ml, p-value 0.01) as compared to control group (519.75±24.5 to 522.58±26.63 ng/ml, p-value 0.64). Mean ß-endorphin levels increased significantly (33±5.52pg/ml to 43.27pg/ml, p-value <  0.0001) as compared to control group (34.78±4.1pg/ml to 36.33pg±4.07pg/ml p-value 0.27). Interleukin-6 decreased significantly in intervention group (2.2±0.5 ng/ml to 1.35±0.32 ng/ml, p-value <  0.0001) as compared to control group (2.03±0.37 to 2.17±0.34 ng/ml p-value 0.25). BDNF increased significantly in intervention group (52.24±6.71 to 63.25±13.48 ng/ml p-value 0.004) as compared to control group (53.23±5.82 to 54.42±5.66 ng/ml p-value 0.54). ROS decreased significantly in intervention group (1596.19±179.14 to 1261±244.31 RLU/min/104 neutrophils p-value 0.0001) as compared to control group (1577.5±172.02 to 1662.5±84.75 RLU/min/104 neutrophils p-value 0.16). CONCLUSIONS: A short term course of Meditation was associated with significant improvement in brain oxygenation and QOL along with a reduction in IOP and stress markers. Meditation may be a useful as an adjunct to standard treatment in patients with POAG and potentially decrease the risk of glaucoma progression.

Mindfulness Meditation Reduces Intraocular Pressure, Lowers Stress Biomarkers and Modulates Gene Expression in Glaucoma: A Randomized Controlled Trial.

BACKGROUND: Reducing intraocular pressure (IOP) in primary open-angle glaucoma (POAG) is currently the only approach to prevent further optic nerve head damage. However, other mechanisms such as ischemia, oxidative stress, glutamate excitotoxicity, neurotrophin loss, inflammation/glial activation, and vascular dysregulation are not addressed. Because stress is a key risk factor affecting these mechanisms, we evaluated whether mindfulness-based stress reduction can lower IOP and normalize typical stress biomarkers. MATERIALS AND METHODS: In a prospective, randomized trial 90 POAG patients (180 eyes; age above 45 y) were assigned to a waitlist control or mindfulness meditation group which practiced daily for 21 days. We measured IOP (primary endpoint), quality of life (QOL), stress-related serum biomarkers [cortisol, ß-endorphins, IL6, TNF-α, brain-derived neurotrophic factor (BDNF), reactive oxygen species (ROS), total antioxidant capacity (TAC)], and whole genome expression. RESULTS: Between-group comparisons revealed significantly lowered IOP in meditators (OD: 18.8 to 12.7, OS 19.0 to 13.1 mm Hg) which correlated with significantly lowered stress-biomarker levels including cortisol (497.3 to 392.3 ng/mL), IL6 (2.8 to 1.5 ng/mL), TNF-α (57.1 to 45.4 pg/mL), ROS (1625 to 987 RLU/min/104 neutrophils), and elevated ß-endorphins (38.4 to 52.7 pg/mL), BDNF (56.1 to 83.9 ng/mL), and TAC (5.9 to 9.3) (all P<0.001). These changes correlated well with gene expression profiling. Meditators improved in QOL (P<0.05). CONCLUSIONS: A short course of mindfulness-based stress reduction by meditation in POAG, reduces IOP, improves QOL, normalizes stress biomarkers, and positively modifies gene expression. Mindfulness meditation can be recommended as adjunctive therapy for POAG.

Yoga- and meditation-based lifestyle intervention increases neuroplasticity and reduces severity of major depressive disorder: A randomized controlled trial.

BACKGROUND: Current interventions for major depressive disorder (MDD) are suboptimal, and only one third respond to them on initial treatment. Neuroplasticity theories are the basis for several emerging treatments. Evidence on the impact of yoga, a well-known mind-body intervention, on neuroplasticity in MDD is limited. OBJECTIVES: To determine the effects of 12-week yoga- and meditation-based lifestyle intervention (YMLI) on depression severity and systemic biomarkers of neuroplasticity in adult MDD patients on routine drug treatment. METHODS: A total of 58 MDD patients were randomized into yoga or control group. The severity of depression was assessed with Beck Depression Inventory-II scale (BDI-II). Blood samples were collected before and after intervention for the measurement of the biomarkers that characterize neuroplasticity, including mind-body communicative and cellular health biomarkers. RESULTS: There was a significant decrease [difference between means, (95% CI)] in BDI-II score [-5.83 (-7.27, -4.39), p < 0.001] and significant increase in BDNF (ng/ml) [5.48 (3.50, 7.46), p < 0.001] after YMLI compared to control group. YMLI significantly increased DHEAS, sirtuin 1, and telomerase activity levels, and decreased cortisol, and IL-6 levels, in addition to decreasing DNA damage and balancing oxidative stress. Multiple regression analyses were used to associate neuroplasticity biomarkers with depression severity. A 'post-intervention change in BDNF' x 'group' interaction indicated that yoga group had more BDNF in association with less BDI-II scores relative to controls. Increased sirtuin 1 and telomerase activity and decreased cortisol significantly predicted this association (all p < 0.05). CONCLUSION: These results suggest that decrease in depression severity after YMLI in MDD is associated with improved systemic biomarkers of neuroplasticity. Thus YMLI can be considered as a therapeutic intervention in MDD management.