Sustained pigmentation causes DNA damage and invokes translesion polymerase Polκ for repair in melanocytes.

Melanin protects skin cells from ultraviolet radiation-induced DNA damage. However, intermediates of eumelanin are highly reactive quinones that are potentially genotoxic. In this study, we systematically investigate the effect of sustained elevation of melanogenesis and map the consequent cellular repair response of melanocytes. Pigmentation increases γH2AX foci, DNA abasic sites, causes replication stress and invokes translesion polymerase Polκ in primary human melanocytes, as well as mouse melanoma cells. Confirming the causal link, CRISPR-based genetic ablation of tyrosinase results in depigmented cells with low Polκ levels. During pigmentation, Polκ activates replication stress response and keeps a check on uncontrolled proliferation of cells harboring melanin-damaged DNA. The mutational landscape observed in human melanoma could in part explain the error-prone bypass of DNA lesions by Polκ, whose absence would lead to genome instability. Thereby, translesion polymerase Polκ is a critical response of pigmenting melanocytes to combat melanin-induced DNA alterations. Our study illuminates the dark side of melanin and identifies (eu)melanogenesis as a key missing link between tanning response and mutagenesis, mediated via the necessary evil translesion polymerase, Polκ.

Constitutive hyperactivity of histone deacetylases enhances radioresistance in Lepidopteran Sf9 insect cells.

BACKGROUND: Lepidopteran insect cells withstand multifold higher radiation doses and suffer far less DNA damage despite carrying numerous structural/functional homologies with mammalian cells. Since DNA-histone interactions significantly influence radiation-induced DNA damage, we investigated the role of histones in insect cell radioresistance. METHODS: Modified comet assay was used to assess the γ-radiation-induced DNA damage following serial histone depletion by varied salt concentrations. Acid-Urea-Triton (AUT) gel analysis combined with in silico predictions was used to compare mammalian and insect histones and acetylation status while HDAC activity was assessed/modified for studying the latter's role in radioresistance. Cell death was measured by morphological analysis and flow cytometry. RESULTS: High-salt extraction pattern from Sf9 nuclei suggested stronger DNA-histone affinity as the two core histones H2A/H2B could be extracted at much higher (2M) concentration as compared to 1.2M NaCl in mammalian (AA8) cells. Electrophoretic mobility of unirradiated Sf9 cells remained unaltered at all salt concentrations (0.14M-2M NaCl), and radiation-induced DNA damage increased only by 2M-NaCl pre-treatment. In silico analysis confirmed excellent conservation of Lepidopteran H2A/H2B sequence with human histones including comparable N-terminal lysine residues, yet these had ~60% lower acetylation. Importantly, insect cells showed ~70% higher histone deacetylase activity whose inhibition by Trichostatin-A reversed hypo-acetylation state and caused significant radiosensitization, thereby confirming the protective contribution of reduced acetylation. CONCLUSION: Our study reveals that the hypo-acetylated state of well-conserved core histones, maintained by considerable HDAC activity, contributes significantly in Lepidopteran radioresistance. GENERAL SIGNIFICANCE: This investigation shows constitutively high activity of HDACs as a potential radioprotective mechanism existing in insect cells.

Bioinspired Functionalized Melanin Nanovariants with a Range of Properties Provide Effective Color Matched Photoprotection in Skin.

Melanin and related polydopamine hold great promise; however, restricted fine-tunabilility limits their usefulness in biocompatible applications. In the present study, by taking a biomimetic approach, we synthesize peptide-derived melanin with a range of physicochemical properties. Characterization of these melanin polymers indicates that they exist as nanorange materials with distinct size distribution, shapes, and surface charges. These variants demonstrate similar absorption spectra but have different optical properties that correlate with particle size. Our approach enables incorporation of chemical groups to create functionalized polyvalent organic nanomaterials and enables customization of melanin. Further, we establish that these synthetic variants are efficiently taken up by the skin keratinocytes, display appreciable photoprotection with minimal cytotoxicity, and thereby function as effective color matched photoprotective agents. In effect we demonstrate that an array of functionalized melanins with distinct properties could be synthesized using bioinspired green chemistry, and these are of immense utility in generating customized melanin/polydopamine like materials.

Common Yoga Protocol Increases Peripheral Blood CD34+ Cells: An Open-Label Single-Arm Exploratory Trial.

Purpose: Physical inactivity can be a cause of various lifestyle disorders including atherosclerosis, diabetes, hypertension, and cardiovascular diseases (CVDs). Lifestyle modification by the inclusion of Yoga and similar activities has shown beneficial effects on disease prevention and psychological management. However, the molecular mechanism at the cellular level is unknown. This study aims to identify the molecular response at systemic level generated after three months of Common Yoga Protocol (CYP) practice. Methods: A total of 25 healthy adult females were recruited for this study (25 to 55 years). After the drop out of 6 participants at baseline and 2 participants after 1 month; blood samples of 17 participants were assessed. Blood samples were assessed for lipid profile, CD34+ cell enumeration and angiogenesis markers (ie, VEGF, Angiogenin and BDNF) at baseline (before intervention), after one month and after three months of Common Yoga Protocol (CYP) practice. The psychological health of the participants was assessed at baseline and after three months of CYP practice. The psychological tests used were General Health Questionnaire (GHQ), State-Trait Anxiety Inventory (STAI), Trail Making Test A & B, Digit symbol test, Digit symbol substitution test. Results: After 3 months of intervention, blood samples of 17 participants were collected and following results were reported (1) percentage of CD34+ cells increased significantly after 3 months of CYP practice (from 18.18±7.32 cells/µL to 42.48±18.83 cells/µL) (effect size: W, 0.40; 95% CI, p = 0.001) (2) neurogenesis marker, ie, BDNF showed a significant change with time after 3 months of CYP intervention (effect size: W, 0.431, 95% CI; p = 0.002), (3) HDL showed an increasing trend (non-significant) after three months of CYP practice (53.017±1.28 mg/dl to 63.94±5.66 mg/dl) (effect size: W, 0.122; 95% CI; p = 0.126) (4) General Health score (10.64 ± 3.53 to 6.52 ± 3.12) (effect size: d, 0.98; 95% CI; p = 0.001) along with visual and executive function improved (69.94±26.21 to 61.88±28.55 (time taken in seconds)) (effect size: d, 0.582; 95% CI; p = 0.036), also stress and anxiety showed reduction (effect size: d, 0.91; 95% CI; p = 0.002) (5) a significant positive correlation was found between: HDL with VEGF (r = 0.547, p = 0.023) and BDNF (r = 0.538, p = 0.039) after 3 months of intervention; also, a significant positive correlation was found between VEGF with BDNF (r = 0.818, p ≤ 0.001) and Angiogenin (r = 0.946, p ≤ 0.001), also, BDNF was also positively correlated with Angiogenin (r = 0.725, p = 0.002) at both 1 month and 3 months after intervention. Also, VEGF and BDNF showed a significantly negative correlation with stress and anxiety questionnaire after the intervention. Conclusion: The current study provides insights into the molecular response to CYP practice at systemic level. The results suggest that CYP practice indeed increased CD34+ cells in peripheral blood and BDNF also showed a significant change after the intervention. An overall improvement in general health and psychology of the participants was also observed.

Training nonspecialists in clinical evaluation for telepsychiatry using videoconferencing: A feasibility and effectiveness study.

AIMS: Videoconferencing-based telepsychiatry has been used successfully for the assessment and management of psychiatric disorders. However, training mental health professionals through videoconferencing has seldom been attempted. Online decision support systems for diagnosing psychiatric disorders had been developed earlier at the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, as a part of a project for delivering telepsychiatric services to remote areas. The feasibility of videoconferencing for training nonspecialist staff in the use of the online tool to diagnose psychiatric disorders was examined. The effectiveness of training was evaluated using ratings of diagnostic agreement between trainees and trainers and estimations of training costs. METHODS: The Skype platform was used for videoconferences (VCs). Broadband internet connections had bandwidths of 4 mbps and speeds of 512 kbps. A total of 62 training sessions were conducted by the PGIMER team for remote-site teams using role-play techniques and actual patient interviews. RESULTS: Videoconferencing-based training was considered to be convenient, satisfactory, and useful by all the participants. Diagnostic agreement between trainees and trainers was 89%-100%. Such training also appeared to be cost-effective. The main problems encountered were poor connectivity and poor audiovisual quality of the VCs. CONCLUSIONS: Videoconferencing can be feasible and effective for training nonspecialists to diagnose psychiatric disorders.

Effects of one month of Common Yoga Protocol practice appear to be mediated by the angiogenic and neurogenic pathway: A pilot study.

OBJECTIVE: To examine the molecular effects of mindful activities such as yoga and meditation DESIGN: This was an open label single arm exploratory yoga intervention study. STUDY PARTICIPANTS: 64 healthy individuals within the age of 18-60 years were recruited for this one month yoga intervention study. INTERVENTION: Common Yoga Protocol (CYP) is a standardized yoga protocol released by Ministry of AYUSH, India for International Yoga Day. It includes all aspects of yoga i.e. asanas, pranayama and meditation. It is designed for adoption by all age groups for the health of community. OUTCOME MEASURES: The participants were assessed for biochemical parameters including Fasting Sugar and Lipid profile. The molecular markers of neurogenesis (i.e. Brain derived Neurotropic Factor, BDNF) and Angiogenesis (i.e. Vascular Endothelial Growth Factor, VEGF and Angiogenin) along with Amyloid ß (marker related to neuro-degenerative diseases) were assessed. All the assessments were made at baseline and after one month of the intervention. RESULTS: After one month of CYP practice High Density Lipoprotein (HDL) levels increased significantly (p<0.001), although other biochemical parameters i.e. fasting sugar and other lipid assessments were found to be unaltered. Angiogenesis marker, angiogenin was increased significantly (p<0.002), other angiogenesis marker VEGF did not show any change along with BDNF, marker of neurogenesis. Amyloid ß levels were also unaltered. Even though individual levels of VEGF and Amyloid ß did not show any change, proportion of VEGF to Amyloid ß showed a significant increase (p<0.001) after one month of CYP intervention indicating that the change in VEGF levels was significantly higher than the change in Amyloid ß levels. CONCLUSION: CYP practice may influence cell survival pathways mediated by angiogenic and neurogenic cross talk. Hence, CYP can be considered as a preventive measure for diseases associated with impaired angiogenic and neurogenic mechanism. This is the first study to examine the effects of CYP at the molecular level.

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.

The role of Yoga in working from home during the COVID-19 global lockdown.

BACKGROUND: The COVID-19 pandemic has become a major cause of stress and anxiety worldwide. Due to the global lockdown, work, employment, businesses and the economic climate have been severely affected. It has generated stress among people from all sections of society, especially to workers who have been assigned to cater to healthcare service or those constrained to secure daily essential items. It is widely perceived that elderly or those affected by diabetes, hypertension and other cardiovascular diseases are prone to COVID-19. As per an ongoing survey, the initial data shows that the above-mentioned anxiety and stress cause insomnia, and has the considerable potential to weaken the immune system, the sole protection against the virus. OBJECTIVE: This study focuses on the need of Yoga practice at work places and at home during the global lockdown due to the COVID-19 pandemic. METHODS: Literature was searched using PubMed and Google Scholar for COVID-19-related stress and anxiety at work and society due to the worldwide lockdown. The predisposing comorbidities, viral mechanism of action and treatment regimen were also searched. Yoga-based intervention studies and online programs were also searched. RESULTS: As the lockdown cannot last forever and workplaces will have to be functional soon, there is an increased possibility of recurrent infection. Therefore, Yoga can provide the necessary tool for risk reduction, amelioration of stress and anxiety and strengthening of the immune function. The online platforms provide a good media for Yoga training at work places and homes. CONCLUSION: Due to social distancing norms, the availability of Yoga trainers has become restricted. Yoga practice is actively sought to achieve reduced anxiety and stress so that improved sleep may positively impact immunity. As a consequence, there is a spurt in social media, catering to daily online Yoga sessions which apparently prove useful in providing accessible means to achieve mental as well as physical well-being.

Primer for Mainstreaming Mind-Body Techniques for Extreme Climates-Insights and Future Directions.

Background: The deprivation of oxygen reaching the tissues (also termed as hypoxia) affects the normal functioning of the body. This results in development of many diseases like ischemia, glaucoma, MCI (Mild Cognitive Impairment), pulmonary and cerebral edema, stress and depression. There are no effective drugs that can treat such diseases. Despite such failure, alternative interventions such as mind-body techniques (MBTs) have not been adequately investigated. Methods: The first part of this review has been focused on philosophical aspects of various MBTs besides evolving an ayurgenomic perspective. The potential of MBTs as a preventive non-pharmacological intervention in the treatment of various general and hypoxic pathologies has been further described in this section. In the second part, molecular, physiological, and neuroprotective roles of MBTs in normal and hypoxic/ischemic conditions has been discussed. Results: In this respect, the importance of and in vivo studies has also been discussed. Conclusions: Although several studies have investigated the role of protective strategies in coping with the hypoxic environment, the efficacy of MBTs at the molecular level has been ignored.

Management of Type II Diabetes by Modulating the Modifiable Risk Factors: A Future Roadmap for Prevention of Cerebrovascular Complications.

BACKGROUND: Indian Diabetes Risk Score (IDRS) is a screening tool for quantifying the risk of diabetes mellitus (DM) development in the Indian population. The present study has evaluated the level of risk of developing DM in Chandigarh and Panchkula based on the IDRS score. METHODS: As a part of a national diabetes control trial funded by the Ministry of Health and Family Welfare (MoHFW) and the Ministry of AYUSH, Government of India, 1,916 participants from the Chandigarh and Panchkula regions were assessed for the risk of developing DM. Risk assessment was done on the basis of the IDRS score which includes age, family history, waist circumference, and physical activity as its contributing factors. Participants with an IDRS score <30 were in the low-risk category, those with 30 to 50 were in the moderate-risk category, and those with >60 were in the high-risk category for DM. RESULTS: Out of the 1,916 screened respondents (59.86% females and 40.14% males), 894 participants (46.65%) were at a high risk for DM (IDRS >60), 764 (39.87%) were at a moderate risk (IDRS = 30-60), and 258 (13.46%) were at a low risk (IDRS <30). Waist circumference contributed to 35.90% of the high-risk category followed by age (19.67%) and physical activity (11.67%). Age and waist circumference also showed a strong correlation with the total IDRS score. CONCLUSION: The Chandigarh and Panchkula population showed a high tendency to develop DM based on the IDRS score. Modifiable risk factors such as waist circumference and physical activity were the major contributing factors. Apart from the modifiable risk factors, age was also another major contributing risk factor. Based on these outcomes, lifestyle modifications like yoga and exercise can be proposed for this population as a preventive approach to reduce the risk of developing DM and other associated cerebrovascular complications.

Distribution of glycated haemoglobin and its determinants in Indian young adults.

AIM: The aim of the present study is to understand the distribution of A1c in four different age groups in young adults and its relation to other co-variants. METHODS: The countrywide data was collected in 2017 in Individuals with high risk analysed by Indian Diabetes Risk Score (IDRS) and self-declared diabetics were identified after screening a sample of 240,968 individuals from rural (4 villages of about 500 adults each) and urban (4 census enumeration blocks of about 500 adults each) population spanning 65 districts of 29 states/UTs of Indian subcontinent. Blood tests and other detailed assessments were carried out on this selected group. This study presents the analysis of the A1c values of 2862 young adults (<35 years). RESULTS: In the age group of 31-34 years, the proportion of Diabetes (22.36%) and Prediabetes (9.86%) was higher in comparison with younger age groups. Also, Diabetes (7.3%) and Prediabetes (22%) were highest among those who had parental history of DM in both parents as compared to those with Diabetes history in one parent [Diabetes (7.1%) or Prediabetes (19.0%)] and no Diabetes Parental History (Diabetes (7.3%) and Prediabetes (18.3%) cases. BMI was found to play a significant positive correlation with Diabetes and Prediabetes (p < 0.001) with range of A1c. CONCLUSION: Age, BMI and parental history were found to be correlated with A1c levels in IDRS screened high-risk population. With increasing age, the proportion of Diabetics and Prediabetics also increased with positive correlation of age with A1c levels.

Erratum: Prevalence and Awareness of Stroke and Other Comorbidities Associated with Diabetes in Northwest India.

[This corrects the article DOI: 10.1055/s-0040-1709369.].

Prevalence and Awareness of Stroke and Other Comorbidities Associated with Diabetes in Northwest India.

Objectives The main purpose of this study is to investigate the prevalence of comorbid conditions in diabetic, prediabetic, and nondiabetic individuals. Additionally, the current study examines the levels of awareness of those comorbidities among North Indian population. Methods As a part of a national study (Niyantrit Madhumeh Bharat [NMB] screening program), different comorbidity parameters were screened in the northern part of India between April and September 2017. There were 1,215 participants recruited in this study. Biochemical analyses of hemoglobin A1c (HbA1c) were conducted on the study subjects. Subsequently, the study subjects were divided into diabetic, prediabetic, and nondiabetic groups based on their HbA1c results. Results The study analysis reveals a higher prevalence of peripheral vascular disease (21.2%), ocular diseases (18%), and hypertension (13.4%) in diabetics with other comorbidities. Furthermore, the study found that a vast majority of the participants were unaware of the presence of hypertension (67.2%), dyslipidemia (84.5%), kidney disease (95.2%), peripheral vascular disease (34.5%), and stroke (95.1%). Conclusion The study concluded that in the northern India, the prevalence of multiple comorbid conditions, such as peripheral vascular disease and hypertension, is higher among diabetic population. Also, the level of awareness of diabetic comorbidities is surprisingly low, which has implications for policymakers, health practitioners, and educators of alternate medicine to increase awareness about diabetes, comorbid conditions, health risk, and possible solution at community and rural level, such as periodic screening programs in this population.

Delineating the Effects of Ionizing Radiation on Erythropoietic Lineage-Implications for Radiation Biodosimetry.

The overall lethality/morbidity of ionizing radiation exposure involves multiple forms of inhibitory or cytotoxic effects that may manifest in different tissues with a varying dose and time response. One of the major systemic effects leading to lethality of radiation includes its suppressive effect on hematopoiesis, which could be observed even at doses as low as 1-2 Gy, whereas effects on gastrointestinal and nervous systems appear at relatively higher doses in the same order. This article reviews the effects of radiation on the three distinct stages of erythropoiesis-formation of erythroid progenitor cells, differentiation of erythroid precursor cells, and terminal maturation. During these stepwise developmental processes, erythroid progenitor cells undergo rapid expansion to form terminally differentiated red blood cells that are continuously replenished from bone marrow into the circulating peripheral blood stream. Cellular radiation response depends upon many factors such as cell lineage, rate of proliferation, and differentiation status. Therefore, we discuss radiation-induced alterations during the progenitor, precursor, and terminal maturation stages and the implications thereof. Since biomarkers of ionizing radiation exposure in human populations are of great interest for assessing normal tissue injury as well as for biodosimetry in the event of accidental or incidental radiation exposures, we also highlight blood-based biomarkers that have potential utility for medical management.

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.

Microbial alkaline proteases: Optimization of production parameters and their properties.

Proteases are hydrolytic enzymes capable of degrading proteins into small peptides and amino acids. They account for nearly 60% of the total industrial enzyme market. Proteases are extensively exploited commercially, in food, pharmaceutical, leather and detergent industry. Given their potential use, there has been renewed interest in the discovery of proteases with novel properties and a constant thrust to optimize the enzyme production. This review summarizes a fraction of the enormous reports available on various aspects of alkaline proteases. Diverse sources for isolation of alkaline protease producing microorganisms are reported. The various nutritional and environmental parameters affecting the production of alkaline proteases in submerged and solid state fermentation are described. The enzymatic and physicochemical properties of alkaline proteases from several microorganisms are discussed which can help to identify enzymes with high activity and stability over extreme pH and temperature, so that they can be developed for industrial applications.

Diagnostic accuracy and feasibility of a net-based application for diagnosing common psychiatric disorders.

A net-based application, which enables users to diagnose and manage common psychiatric disorders independently, was developed. Diagnostic accuracy and reliability of the application were compared with the Mini International Neuropsychiatric Interview among 274 adult outpatients. The screening sub-module of the application had high sensitivity, specificity and negative predictive values for most disorders, but low positive predictive values for several disorders. The criteria-based diagnostic sub-module demonstrated moderate to substantial agreement (kappa>0.50) for all 4 broad categories and 10 of the 18 individual disorders included. Diagnostic agreement was, however, low (kappa<0.4) for most of the disorders comprising the broad category of 'neurotic and stress-related disorders'. Low sensitivity was also observed among these disorders, though specificity, and positive and negative predictive values were high for most disorders. Inter-rater reliability of the application's diagnoses was high. Symptom-severity and functional status scores correlated significantly with those on standard scales. Average time taken was 5min for screening and 20min for detailed diagnostic assessment. A majority of the patients, their relatives and interviewers were satisfied with the assessment. The results suggest that with further refinement the application could be suitable for use as a net-based diagnostic tool for psychiatric disorders.