ALS plasma reduces the viability of NSC34 cells via altering mRNA expression of VEGF: A short report.

Introduction: Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder that progressively leads to motor neuron degeneration at the neuromuscular junctions, resulting in paralysis in the patients. The clinical diagnosis of ALS is time taking and further delays the therapeutics that can be helpful if the disease is diagnosed at an early stage. Changes in plasma composition can be reflected upon CSF composition and hence, can be used to study the diagnosis and prognosis markers for the disease. Aim: To develop a simple model system using motor neuron like cell line after plasma induction. Method: Neuroblastoma × Spinal Cord hybridoma cell line (NSC34) was cultured under appropriate conditions. 10% ALS patients' plasma was added to the media, and cells were conditioned for 12 h. Cell survival analysis and differential gene expression of a panel of molecules (published previously, VEGF, VEGFR2, ANG, OPTN, TDP43, and MCP-1) were done. Results: ALS patients' plasma impacted the life of the cells and reduced survival to nearly 50% after induction. VEGF was found to be significantly down-regulated in the cells, which can be explained as a reason for reduced cell survival. Conclusion: ALS plasma altered the expression of an essential neuroprotective and growth factor VEGF in NSC34 cells leading to reduced viability.

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.

War-Related Mental Health Issues and Need for Yoga Intervention Studies: A Scoping Review.

Conflicts and humanitarian crises lead to serious mental health disorders, including depression, anxiety, stress, and cognitive decline. Exposure to these circumstances in early life can lead to the development of disorders such as mild cognitive impairment, dementia, and Alzheimer's disease (AD), for which no treatments are available. In this review, various research papers have been compiled to develop an understanding about mental health of population affected due to wars and conflicts and how stress and depression can accelerate the development of dementia and AD. Due to failure of drugs in the treatment of dementia and AD, yoga and mindfulness-based approach has been proposed for future investigations. Although studies have shown that yoga and mindfulness can be helpful in the management of stress, anxiety, depression, and posttraumatic stress disorder in the war-afflicted areas, limited mechanistic studies in yoga and mindfulness remain the chief cause precluding its clinical application in such warzones. The molecular studies in the field of yoga can be undertaken by targeting these warzones. This review provides a scientific evaluation of mind-body techniques as a justification for mental health rehabilitation in the war-afflicted zones in face of failed clinical trials for various drugs. This may help reduce the risk of developing dementia and AD in this susceptible population.

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.

Association of Plasma Biomarkers for Angiogenesis and Proteinopathy in Indian Amyotrophic Lateral Sclerosis Patients.

Background Amyotrophic lateral sclerosis (ALS) is a rare motor neuron disease with progressive degeneration of motor neurons. Various molecules have been explored to provide the early diagnostic/prognostic tool for ALS without getting much success in the field and miscellaneous reports studied in various population. Objective The study was aimed to see the differential expression of proteins involved in angiogenesis (angiogenin [ANG], vascular endothelial growth factor [VEGF], vascular endothelial growth factor receptor 2 [VEGFR2], etc), proteinopathy (transactive response DNA binding protein-43 [TDP-43] and optineurin [OPTN]), and neuroinflammation (monocyte chemoattractant protein-1[MCP-1]) based on the characteristics of ALS pathology. Though, suitable panel based on protein expression profile can be designed to robust the ALS identification by enhancing the prognostic and diagnostic efficacy for ALS. Methods A total of 89 ALS patients and 98 nonneurological controls were analyzed for the protein expression. Expression of angiogenic (VEGF, VEGFR2, and ANG), neuroinflammation (MCP-1), and proteinopathy (TDP-43 and OPTN) markers were estimated in plasma of the participants. Proteins were normalized with respective value of total protein before employing statistical analysis. Results Analysis has exhibited significantly reduced expression of angiogenic, proteinopathy, and neuroinflammation biomarkers in ALS patients in comparison to controls. Spearman's correlation analysis has showed the positive correlation to each protein. Conclusion Altered expression of these proteins is indicating the prominent function in ALS pathology which may be interdependent and may have a synergistic role. Hence, a panel of expression can be proposed to diagnose ALS patient which may also suggest the modulation of therapeutic strategy according to expression profile of patient.

Higher Perceived Stress and Poor Glycemic Changes in Prediabetics and Diabetics Among Indian Population.

Diabetes mellitus (DM) is a chronic metabolic disorder with significant co-morbidities and healthcare burdens. Many large studies have investigated the association between perceived stress and DM; however, none investigated this in a larger Indian population. We hypothesized stress as one of the reasons for the progression of people with prediabetes into DM. The present study was, therefore, planned to report on associations between perceived stress and blood glucose markers stratified by diabetic status. The current descriptive study was a subset analysis of the nationwide cross-sectional survey, conducted in all Indian zones under the National Multicentric Diabetes Control Program. The study examined the perceived stress levels using a perceived stress scale (PSS-10) in people with prediabetes (n=649) and DM (n=485) and then segregated them into three categories (minimum, moderate, and severe). Blood glucose markers (fasting blood glucose, postprandial blood glucose, and HbA1c) were evaluated to report their association with the perceived stress. The study revealed a significantly higher HbA1c level in people with prediabetes, particularly those with severe perceived stress (6.12 ± 0.27) compared to other categories. Those with DM had a higher fasting blood glucose level, particularly with severe perceived stress (239.28 ± 99.52). An increased HbA1c level is noted in severely stressed people with prediabetes, requiring a comprehensive analysis with a longitudinal study of the role of perceived stress in the progression of prediabetes into DM. Additionally, higher fasting blood glucose levels in patients with DM and severe perceived stress suggests the need for establishing comprehensive diabetic care inclusive of stress management.

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.

Angiogenesis-Centered Molecular Cross-Talk in Amyotrophic Lateral Sclerosis Survival: Mechanistic Insights.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is characterized with progressive muscle atrophy. We have attempted to establish the link between angiogenesis and cellular survival in the pathogenesis of ALS by compiling evidence described in various scientific reports. The phenotypes of human ALS have earlier been captured in the mutant SOD1 mice as well as by targeted deletion of the hypoxia response element (HRE) from the promoter of the mouse gene for vascular endothelial growth factor (VEGF). Indirect evidence shows that angiogenesis can help prevent oxidative stress, and hence, enhance cell survival. VEGF and angiogenin chiefly regulate the process of angiogenesis. Transactive response DNA-binding protein 43 (TDP-43) is usually found inside the nucleus, but in large number of cases of ALS, it accumulates in the cytoplasm (TDP-43 proteinopathy). Interestingly, TDP-43 proteinopathy is found to be aggravated in the presence of the OPTN mutation, which is the genetic factor that is responsible for such accumulation. Interaction of TDP-43 with progranulin can further affect the angiogenesis in ALS patients by regulating activity of VEGF receptors, but conclusive evidence is needed to establish its role in pathogenesis of ALS. Certain mutations in UBQLN2 and UBQLN4 indicate that ubiquitination has a role in ALS pathobiology, but its link to angiogenesis has not been adequately studied. Recent studies have shown that several mutations in RNA-binding proteins (RBPs) can also cause ALS. Conclusively, in this review, we have attempted to argue the role of angiogenesis in enhanced ALS survival rate is probably regulated with the activation of NF-κß. Additionally, interaction between OPTN and TDP-43 can also impact the transcription of various angiogenic molecules. Whether targeting angiogenic substances or TDP-43 can provide clues about extending ALS survival rate, in combination with current treatments, can only be evaluated after additional studies.

Partitioning of radiological, stress and biochemical changes in pre-diabetic women subjected to Diabetic Yoga Protocol.

BACKGROUND: Yoga is an ancient system of wellness with Asana and Pranayama as its most popular and propagated modules for management of lifestyle disorders. OBJECTIVES: The aim of the study was to characterise the liver abnormalities, biochemical changes, and stress levels after Yoga intervention in prediabetic females. MATERIALS AND METHODS: 37 females were randomly divided into Yoga practising and non-practising control groups. The Yoga practising group performed Diabetic Yoga Protocol (DYP) for 3 months. Parameters including size of liver, fatty infiltration, and grade of severity were measured using ultrasonography along with biochemical parameters and stress levels at baseline and after Yoga practice. RESULTS: The glycosylated hemoglobin (HbA1c) and glucose levels were found significantly reduced in prediabetic (p = 0.015) women after practising DYP, although cholesterol levels increased in menopausal women. No escalation of fatty liver was noted among women practising DYP. CONCLUSION: DYP reduced the HbA1c and stress levels and therefore, could be a cost-effective tool for preventing prediabetes to diabetes progression.

Is Brain-Derived Neurotrophic Factor: A Common Link Between Neurodegenerative Disorders and Cancer?

BACKGROUND: Cancer is a common disease caused by the excessive proliferation of cells, and neurodegenerative diseases are the disorders caused due to the degeneration of neurons. Both can be considered as diseases caused by the dysregulation of cell cycle events. A recent data suggests that there is a strong inverse association between cancer and neurodegenerative disorders. There is indirect evidence to postulate Brain-derived Neurotrophic Factor (BDNF) as a potential molecular link in this association. DISCUSSION: The BDNF levels are found to be downregulated in many neurodegenerative disorders and are found to be upregulated in various kinds of cancers. The lower level of BDNF in Alzheimer's and Parkinson's disease has been found to be related to cognitive and other neuropsychological impairments, whereas, its higher levels are associated with the tumour growth and metastasis and poor survival rate in the cancer patients. CONCLUSION: In this review, we propose that variance in BDNF levels is critical in determining the course of cellular pathophysiology and the development of cancer or neurodegenerative disorder. We further propose that an alternative therapeutic strategy that can modulate BDNF expression, can rescue or prevent above said pathophysiological course. Larger studies that examine this link through animal studies are imperative to understand the putative biochemical and molecular link to wellness and disease.

Creating a role model for "Academicians" Social Responsibility (ASR) synergizing with Swachh Bharat Abhiyaan: A campus hygiene initiative by PGIMER, Chandigarh.

BACKGROUND: The state of disarray from unhygienic conditions and excessive litter throughout urban highways, alleyways, and byways across rural and urban localities of India is abysmal. Such unsanitary conditions impinge upon the future health and welfare of its citizens, tourists and economic development. PURPOSE: The NRL volunteered PGIMER's campus hygiene initiative" is a pioneering effort spearheaded in compliance with Indian Prime Minister's call that citizens of India work together to establish a cleaner and healthier environment. METHODS: A group of 15 highly motivated students in the Neuroscience Division of the PGIMER, worked together vigorously 2 hours a week to affect a cleaner urban environment in the city. RESULT: The results were national Kayakalp and Skoch award to PGIMER as the cleanest hospital in the country, the vendors or patients no longer litter around the campus, the pot holes have been converted into greener patches, signs board adorn the campus. CONCLUSION: To inspire citizens through faculty- student led sanitation programs.

Development and implementation of South Asia's first heat-health action plan in Ahmedabad (Gujarat, India).

Recurrent heat waves, already a concern in rapidly growing and urbanizing South Asia, will very likely worsen in a warming world. Coordinated adaptation efforts can reduce heat's adverse health impacts, however. To address this concern in Ahmedabad (Gujarat, India), a coalition has been formed to develop an evidence-based heat preparedness plan and early warning system. This paper describes the group and initial steps in the plan's development and implementation. Evidence accumulation included extensive literature review, analysis of local temperature and mortality data, surveys with heat-vulnerable populations, focus groups with health care professionals, and expert consultation. The findings and recommendations were encapsulated in policy briefs for key government agencies, health care professionals, outdoor workers, and slum communities, and synthesized in the heat preparedness plan. A 7-day probabilistic weather forecast was also developed and is used to trigger the plan in advance of dangerous heat waves. The pilot plan was implemented in 2013, and public outreach was done through training workshops, hoardings/billboards, pamphlets, and print advertisements. Evaluation activities and continuous improvement efforts are ongoing, along with plans to explore the program's scalability to other Indian cities, as Ahmedabad is the first South Asian city to address heat-health threats comprehensively.