Extrahelical Binding Site for a 1H-Imidazo[4,5-c]quinolin-4-amine A3 Adenosine Receptor Positive Allosteric Modulator on Helix 8 and Distal Portions of Transmembrane Domains 1 and 7.

This study describes the localization and computational prediction of a binding site for the A3 adenosine receptor (A3AR) positive allosteric modulator 2-cyclohexyl-1H-imidazo[4,5-c]quinolin-4-(3,4-dichlorophenyl)amine (LUF6000). The work reveals an extrahelical lipid-facing binding pocket disparate from the orthosteric binding site that encompasses transmembrane domain (TMD) 1, TMD7, and Helix (H) 8, which was predicted by molecular modeling and validated by mutagenesis. According to the model, the nearly planar 1H-imidazo[4,5-c]quinolinamine ring system lies parallel to the transmembrane segments, inserted into an aromatic cage formed by π-π stacking interactions with the side chains of Y2847.55 in TMD7 and Y2938.54 in H8 and by π-NH bonding between Y2847.55 and the exocyclic amine. The 2-cyclohexyl group is positioned "upward" within a small hydrophobic subpocket created by residues in TMDs 1 and 7, while the 3,4-dichlorophenyl group extends toward the lipid interface. An H-bond between the N-1 amine of the heterocycle and the carbonyl of G291.49 further stabilizes the interaction. Molecular dynamics simulations predicted two metastable intermediates, one resembling a pose determined by molecular docking and a second involving transient interactions with Y2938.54; in simulations, each of these intermediates converges into the final bound state. Structure-activity-relationships for replacement of either of the identified exocyclic or endocyclic amines with heteroatoms lacking H-bond donating ability were consistent with the hypothetical pose. Thus, we characterized an allosteric pocket for 1H-imidazo[4,5-c]quinolin-4-amines that is consistent with data generated by orthogonal methods, which will aid in the rational design of improved A3AR positive allosteric modulators. SIGNIFICANCE STATEMENT: Orthosteric A3AR agonists have advanced in clinical trials for inflammatory conditions, liver diseases, and cancer. Thus, the clinical appeal of selective receptor activation could extend to allosteric enhancers, which would induce site- and time-specific activation in the affected tissue. By identifying the allosteric site for known positive allosteric modulators, structure-based drug discovery modalities can be enabled to enhance the pharmacological properties of the 1H-imidazo[4,5-c]quinolin-4-amine class of A3AR positive allosteric modulators.

Positive Psychological Changes at High Altitude Shown by the Low Landers after the Yoga Intervention-Sudarshan Kriya Yoga (SKY).

Background: Immediate assent to high altitude affects the cognitive performance and mood of an individual, which is followed by depression and anxiety. It also affects the sleep quality, general health, and happiness quotient of an individual. Sudarshan Kriya Yoga (SKY) is a cyclical breathing technique, which has been proven successful in managing stress, depression, anxiety, and helps in the improvement of sleep quality. Purpose: The current study was to understand the role of SKY meditation on psychological parameters, happiness quotient of low landers at high altitude (Leh). Methods: It is a two-armed pre-post study with experimental and control group both are lowlanders, and their psychological parameters are being assessed when they immediately assent to high altitude (Leh). There are two groups experimental group (SKY) was from AOL SKY-AMP and has prior SKY meditation experience. The control group does not have any yoga or meditation experience. SKY-AMP is a 4 days protocol done at high altitude by the SKY group. Both groups reach Leh through air mode transportation. Results: Oxford Happiness Questionnaire (OHQ) showed a significant result in the SKY group with P ≤ .001, whereas it is nonsignificant in the control group. We also observed anthropometric and physiological changes in the participants showing significant effects on weight, BMI, waist circumference, hip circumference, and blood pressure; with no significant effect in the control group. It is one of the first studies done with both two groups, where yoga and meditation are done at high altitude and then seen the changes in the groups at physical and psychological level. Conclusion: Yogic practices can be helpful in having positive psychological change in the lowlanders at high altitude.

New paradigms in purinergic receptor ligand discovery.

The discovery and clinical implementation of modulators of adenosine, P2Y and P2X receptors (comprising nineteen subtypes) have progressed dramatically in ∼50 years since Burnstock's definition of purinergic signaling. Although most clinical trials of selective ligands (agonists and antagonists) of certain purinergic receptors failed, there is a renewed impetus to redirect efforts to new disease conditions and the discovery of more selective or targeted compounds with potentially reduced side effects, such as biased GPCR agonists. The elucidation of new receptor and enzyme structures is steering rational design of potent and selective agonists, antagonists, allosteric modulators and inhibitors. A2A adenosine receptor (AR) antagonists are being applied to neurodegenerative conditions and cancer immunotherapy. A3AR agonists have potential for treating chronic inflammation (e.g. psoriasis), stroke and pain, as well as cancer. P2YR modulators are being considered for treating inflammation, metabolic disorders, acute kidney injury, cancer, pain and other conditions, often with an immune mechanism. ADP-activated P2Y12R antagonists are widely used as antithrombotic drugs, while their repurposing toward neuroinflammation is considered. P2X3 antagonists have been in clinical trials for chronic cough. P2X7 antagonists have been in clinical trials for inflammatory diseases and depression (compounds that penetrate the blood-brain barrier). Thus, purinergic signaling is now recognized as an immense regulatory system in the body for rebalancing tissues and organs under stress, which can be adjusted by drug intervention for therapeutic purposes. The lack of success of many previous clinical trials can be overcome given more advanced pharmacokinetic and pharmacodynamic approaches, including structure-based drug design, prodrugs and biased signaling. This article is part of the Special Issue on "Purinergic Signaling: 50 years".

Effect of yoga on the social responsiveness and problem behaviors of children with ASD in special schools: A randomized controlled trial.

CONTEXT: Autism spectrum disorder (ASD) is the most common neurodevelopmental disorder and is increasingly reported among school-age children in India. Many children with ASD attend special schools which extend support for learning basic functional and academic skills. Problem behaviors and lack of social responsiveness are frequently associated with children with ASD in a school environment. Many evidence-based studies have explored various interventions in mitigating the lack of social responsiveness and problem behaviors in children. Few studies have examined the impact of yoga on social responsiveness and problem behaviors in special schools. OBJECTIVE: The objective of the study was to highlight the effect of school-based yoga on the social responsiveness and problem behaviors of children with ASD in special schools. Forty-three children with ASD from four special schools participated in the study. DESIGN: A randomized controlled trial (RCT) design was employed for the study. Children with ASD (n = 43) from four special schools were assessed by their teachers for social responsiveness and problem behaviors with the Social Responsiveness Scale-2 (SRS-2) and Aberrant Behavior Checklist-2 (ABC-2) at the baseline and after the yoga intervention. INTERVENTION: Structured yoga of 45 min for 12 weeks was conducted across four special schools with simple yoga practices conducive to children with ASD. RESULTS: Significant changes were observed post-intervention in the mean scores of the social communication aspect in social responsiveness (p = .021), irritability (p = .041), and social withdrawal (p = .047) aspects of problem behaviors.

Effect of Surya Namaskara (Sun Salutation) on mental health, self-control and mindfulness of adolescent school children.

BACKGROUND: A considerable portion of adolescent school children suffer from mental health problems. Low self-control and mindfulness are positively associated with poor mental health. Therefore, the present study was designed to assess the effect of Surya Namaskara (SN) on mental health, self-control, and mindfulness among adolescent school children. METHODS: Sixty-three (39 females) students (mean age = 14.24 years and SD = 0.42 years) in grade nine from a private school in India were recruited as study participants. The design of the present study was a non-randomized two arms design. Section A (N = 33) was selected as the intervention group, whereas section B (N = 30) was considered a control group. Students in the intervention group were given SN for two weeks. The participants were administered the General Health Questionnaire-12 (GHQ-12), Brief Self-control Scale (BSCS), and Mindfulness, Attention and Awareness Scale for Adolescents (MAAS-A) questionnaires at the baseline and after two weeks of intervention. RESULTS: The within-group comparison showed a significant main effect of time in MAAS-A scores. There was also a significant group by time interaction effect for BSCS and MAAS-A scores. Post-hoc analysis showed that the SN group has significantly higher post-BSCS and MAAS-A scores than the control group. Similarly, there was a significantly high BSCS score and MAAS-A score after SN intervention compared to their respective pre-scores. There was no significant change in the GHQ-12 scores in both groups in the pre-post comparison. CONCLUSION: The present study showed that SN improves self-control and mindfulness in adolescent school children.

Effect of yoga on children with autism spectrum disorder in special schools.

Introduction: Yoga as a holistic mind-body intervention is increasingly evaluated for the management of various autism symptoms in children with autism spectrum disorder (ASD). Methodology: Forty-three children with ASD from 4 special schools were randomized into two groups, yoga group: 23 children and control group: 20 children. The yoga group received 12 weeks of yoga intervention in special schools. Results: Significant improvement in the yoga group was noted in the overall autism severity (P < 0.001) as reported by the parents in comparison to the control group. Conclusion: The findings of the study show that yoga can have a positive impact on the symptomatology of autism.

Effect of yoga on cognitive functions and anxiety among female school children with low academic performance: A randomized control trial.

BACKGROUND: To achieve better academic performance, students should improve their cognitive faculties and overcome anxiety. Therefore, the present research was conducted to assess the effect of yoga on the cognitive functions of female adolescents with low academic performance. METHODS: The present study is a randomized control trial (RCT). Eighty-nine female students in the age range of 12-14 years were randomly assigned into two groups [yoga (n = 45); physical exercise (n = 44)] at a school setting. Both groups were assessed before and after on Raven's standard progressive matrices (RSPM), Corsi Block Tapping Test (CBTT), Six Letter Cancellation Test (SLCT), Digit Letter Substitution Test (DLST), Stroop Color and Word Test (SCWT), and State-Trait Anxiety Inventory for Children (STAIC). RESULTS: Findings of the present study showed significant (p < .05) differences in scores of forward CBTT, SWCT, and SLCT in group × time interaction. Both the groups showed significant (p < .05) improvement in SLCT, backward scores of CBTT, and STAIC-T. All outcomes measured were significantly (p < .05) improved in the yoga group except STAIC-S. CONCLUSION: Yoga improves general intelligence, visuospatial working memory, and attention, as well as reduces the anxiety of students with low academic performance. Similarly, physical exercise was also found to be improving visuospatial working memory, sustained attention, and reduce trait anxiety. However, the finding of the present study indicated yoga to be more effective compared to physical exercise in regards to students' fluid intelligence and executive function. Improvement in general intelligence, visuospatial working memory, and attention is expected to positively influence students' academic performance.

Physical Activity, Yoga, and Exercise Prescription for Postpartum and Midlife Weight Management: A Practical Review for Clinicians.

This narrative review is aimed to practically review and evaluate the existing evidence and illuminate the effectiveness of physical activity, yoga, and exercise for postpartum and midlife weight management. A comprehensive review was conducted using electronic databases such as PubMed and google scholar using search terms physical activity, exercise, yoga, postpartum, midlife, weight loss, weight reduction, and all the probable terms. This helped in generating evidence-based information and formulating practical physical activity prescriptions to be used by obstetricians, general clinicians, nutritionists, and other allied healthcare personnel. Overweight and obesity in postpartum and midlife women present long-term health risks and complications. Indulging in optimum physical activity comprising exercise and yoga will help in weight management, increasing muscular strength, and endurance thus improving overall health and well-being. Supplementary Information: The online version contains supplementary material available at 10.1007/s13224-022-01627-w.

Effect of Yoga on the Motor Proficiency of Children with Autism Spectrum Disorder and the Feasibility of its Inclusion in Special School Environments.

Yoga as a movement-based intervention is increasingly considered to improve the motor skills of children with autism spectrum disorder (ASD). However, there is little evidence of the effect of yoga on their motor skills. The current study aims to explore the effect of group yoga program on motor proficiency of children with ASD and feasibility of its inclusion in special schools. Forty-three children with ASD from four special schools were randomized into yoga (n = 23) and control (n = 20) group. A structured yoga program of 45 min for 12 weeks was delivered by trained yoga teachers who also tracked their daily responses. The Bruininks-Oseretsky Test of Motor Proficiency. Second Edition was used to assess both the groups pre- and postintervention. In conclusion, the study highlighted that yoga appears to have a positive impact on the gross motor rather than fine motor proficiency of children with ASD and is feasible to be delivered as group intervention in special schools.

Physical and mental health at high altitude of individuals doing yogic practices.

Objectives: There is an increase trend in the past few years, in the number of people traveling to high altitude for recreational activities such as pilgrims, mountaineering, and climbing and for occupational purposes such as defense and mining which have resulted in increasing in hypoxia conditions and anxiety-related medical problems at high altitude. As it is known that mental stress affects brain and heart functions, a recent research performed on Sudarshan Kriya Yoga (SKY) further validated the effectiveness of SKY on participants (practicing SKY) as compared to control after quantifying mental stress. To study the physiological effect of SKY advance breathing technique when immediately ascends to high altitude, we wanted to study the level of stress and mental well-being of lowlanders at high altitude. Materials and Methods: It is an interventional study performed at high altitudes, with low landers as participants where their biochemical and psychological parameters are being assessed. Results: The result for biochemical parameter cholesterol, triglycerides, low-density lipoproteins (LDLs), high-density lipoproteins (HDLs), very low-density lipoproteins, LDL-HDL ratio, and cholesterol-HDL ratio showed a significant decrease in the pre- and post-analyses values with P ≤ 0.001. Acute mountain sickness (AMS), Warwick-Edinburgh Mental Well-being Scale, and State and Trait Anxiety Inventory (STAI) also show a decreasing trend with significant result in AMS, mental well-being, and non-significant in STAI p value is P = 0.016, P = 0.055, and P = 0.125, respectively. Conclusion: We observed positive outcome both in for biochemical and stress-related parameters with SKY advance program practitioners who have rapidly ascend to high altitude.

Effect of four weeks of integrated yoga intervention on perceived stress and sleep quality among female nursing professionals working at a tertiary care hospital: A pilot study.

BACKGROUND: Studies have reported that significant nursing professionals experience tremendous stress which often affects their sleep quality leading to poor well-being. Yoga being a mind body intervention reported to improve sleep quality and reduce stress. AIM: The present pilot study was designed to assess the effect of yoga on perceived stress and sleep quality of the female nursing professionals working at tertiary care hospital. MATERIALS AND METHODS: Thirty-three apparently healthy nursing staffs in the age range of 30-60 years (mean age 40.60 ± 10.26) were recruited as participants of the study, from a tertiary care hospital in Delhi. Participants were administered perceived stress scale (PSS) and Pittsburgh sleep quality index (PSQI) before and after the yoga intervention. Participants received 4 week of yoga intervention for 45 min/day for 5 days a week. RESULTS: There was a significant reduction on the postscores of PSS (t = 5.86, P < 0.0001, paired t-test) and PSQI (z = -4.38, P < 0.0001, Wilcoxon signed-ranks test) in comparison to prescores. After the yoga intervention, perceived stress reduced by 27.01% and the sleep quality improved by 38.68%. CONCLUSION: The finding of the study suggests effectiveness of yoga in reduction of the perceived stress and improvement of the quality of sleep of the nursing professional. However, the present findings need to be confirmed with further studies with larger sample size and robust research design.

A Comparative Study between Vedic and Contemporary Education Systems using Bio-Energy Markers.

BACKGROUND/AIM: "The destiny of the whole world depends on the children. If you want to see the silver lining on the horizon it is not you and me, but the children who have to be spiritualized" says Swami Satyananda Saraswati. Sri Aurobindo states "Education to be complete must have five principal aspects corresponding to the five principal activities of the human being: the physical, the vital, the mental, the psychic and the spiritual." Vedic education system (VES) focuses on inculcating all facets for overall development of personality. This study is an attempt to understand the lore of Vedic education followed by yoga as a way of lifestyle for physiological well-being and for successful unfoldment of children's personality. MATERIALS AND METHODS: The sample size was 378 (108 VES and 270 contemporary education system [CES]). We have excluded volunteers who had minor health problems from the study. The ethical clearance was taken from SVYASA University Ethics Committee, and informed consent was obtained for each individual undergoing the study. As it was aimed to collect one-time data, the yoga as a lifestyle in VES itself considered as an intervention. Thus, the two systems of educations are compared. The variables are measured using the Electro-photonic Image Bio-Well instrument. RESULTS: Bio-Well variables for VES and CES were compared. There was a significant difference in VES and CES energy level scores, left-right symmetry scores, organ balance, and entropy coefficient scores. CONCLUSIONS: Results suggest that Vedic Education System to be better in the measured parameters compared to Contemporary Education System.

Yoga Practices as an Alternative Training for Physical Fitness in Children With Visual Impairment.

Physical activities provide fundamental benefits to children's health and well-being. They are vital for development and healthy life, but participation of children with visual impairment is limited. Herein, the authors report results of a 16-wk yoga program, evaluating its effects on physical fitness in children with visual impairment. Eighty-three children age 9-16 years (12.37 ± 2.19) participated in a 2-arm, single-blind wait-list-controlled study at a residential school in south India. Participants (yoga group 41, controls 42) were assessed on muscle strength, flexibility, endurance, coordination, and respiratory health. Significant improvements in physical fitness were observed after the yoga intervention (Group × Time interactions for right-hand grip strength, p < .001; sit-up, p < .001; sit and reach, p < .001; bilateral plate tapping, p < .001; and peak expiratory flow rate, p < .001). Left-hand grip strength showed main effects of time, although there were no Group × Time interactions. Results demonstrate yoga's ability to improve a wide range of physical variables in children with visual impairment.

Association between Cyclic Meditation and Creative Cognition: Optimizing Connectivity between the Frontal and Parietal Lobes.

BACKGROUND: Important stages of creativity include preparation, incubation, illumination, and verification. Earlier studies have reported that some techniques of meditation promote creativity but have not specified which stage is enhanced. Here, we report the influence of cyclic meditation (CM) on creative cognition measured by a divergent thinking task. Our aim was to determine the degree of association between the two. METHODS: Twenty-four university students were randomly assigned to an experimental group (CM) and controls (Supine Rest), 35 min/day for 7 days. Creativity performance was assessed pre and post using Abbreviated Torrance Test for Adults (ATTA), while 64-channel electroencephalography (EEG) was used to measure brain activity during both CM/SH and the creativity test. RESULTS: Results indicated that CM training improved creativity performance, producing a shift to predominant gamma activity during creativity compared controls who showed delta activity. Furthermore, the experimental group showed more activation of frontal and parietal regions (EEG leads F3, F4 and P3, P4) than controls, i.e., the regions of the executive network responsible for creative cognition, our particular regions of interest where specialized knowledge is being stored. CONCLUSION: Improvement on creativity test performance indicates that CM increases association and strengthens the connectivity between frontal and parietal lobes, the major nodes of default mode network and executive attention network, enhancing the important stages of creativity such as preparation, incubation, and illumination.

Spiritual Well-Being and Its Relationship with Mindfulness, Self-Compassion and Satisfaction with Life in Baccalaureate Nursing Students: A Correlation Study.

The present study aimed to explore the correlates and predictors of spiritual well-being among nursing students. One hundred and forty-five BSc nursing students were recruited from three nursing colleges in Bangalore, Karnataka, India. Data were collected using SHALOM, FMI, SCS-SF and SWLS questionnaires and analysed by the Pearson correlation test and multiple regression analysis. The results of our study revealed a significant correlation between variables, and a considerable amount of variance was explained by self-compassion, mindfulness and satisfaction with life on personal, communal, environmental and transcendental domains of spiritual well-being.

Effect of yoga practices on psycho-motor abilities among intellectually disabled children.

The children with intellectual disabilities show disorders at motor development and coordination. Hence, the objective of this study was to see the effect of yoga practices on psycho-motor abilities of intellectually disabled children. Seventy intellectually disabled children were divided into experimental group and control group. Both experimental and control group were assessed on the first day and after 12 weeks of the yoga intervention for static balance, eye hand coordination, agility and reaction time. The subjects of experimental group then underwent a training of yoga practices, for 1 hr for a total period of 12 weeks. The result of within group comparison revealed significant improvement in static balance, eye hand coordination, agility, and reaction time (P< 0.001) in subjects of yoga group however no change was observed in control group. The present study demonstrated that 12 weeks of yoga is effective in improving psycho-motor abilities of intellectually disabled children.

Giant enhancement and facile tuning of photoluminescence in a soft anisotropic magneto-gel.

A soft photoluminescent composite, prepared using a nematic liquid crystal and a fluorescent gelator, exhibits a nearly two orders of magnitude increase in fluorescence on addition of superparamagnetic nanoparticles. The internal magnetic field generated leading to an increase in the population of singlet excitons which affects the radiative efficiency, and enhanced ordering of the LC environment are proposed to be responsible for the large increase seen in fluorescence. Also, the nematic nature of the host liquid crystal medium aids in switching of the fluorescence intensity between its anisotropic limits on application of an external electric field with the switch-off time being faster compared to the field-driven switch-on time.

Effect of Yogic Breathing on Accommodate Braille Version of Six-letter Cancellation Test in Students with Visual Impairment.

CONTEXT: Attentional processes tend to be less well developed in the visually impaired, who require special training to develop them fully. Yogic breathing which alters the patterns of respiration has been shown to enhance attention skills. Letter cancellation tests are well-established tools to measure attention and attention span. Here, a modified Braille version of the six-letter cancellation test (SLCT) was used for students with visual impairment (VI). AIM: This study aimed to assess the immediate effects of Bhramari Pranayama (BhPr) and breath awareness (BA) on students with VI. METHODS: This study was a self-as-control study held on 2 consecutive days, on 19 participants (8 males, 11 females), with a mean age of 15.89 ± 1.59 years, randomized into two groups. On the 1st day, Group 1 performed 10 min breath awareness and Group 2 performed Bhramari; on the 2nd day, practices were reversed. Assessments used a SLCT specially adapted for the visually impaired before and after each session. RESULTS: The Braille letter cancellation test was successfully taken by 19 students. Scores significantly improved after both techniques for each student following practices on both days (P < 0.001). BhPr may have more effect on attention performance than BA as wrong scores significantly increased following BA (P < 0.05), but the increase in the score after Bhramari was not significant. CONCLUSIONS: Despite the small sample size improvement in attentional processes by both yoga breathing techniques was robust. Attentional skills were definitely enhanced. Long-term practice should be studied.

Effect of 1-Week Yoga-Based Residential Program on Cardiovascular Variables of Hypertensive Patients: A Comparative Study.

INTRODUCTION: Hypertension (HTN) is an important public health concern and a leading cause of morbidity and mortality worldwide. Yoga is a form of mind-body medicine shown to be effective in controlling blood pressure (BP) and reduces cardiac risk factors in HTN. Integrated approach of Yoga therapy (IAYT) is a residential yoga-based lifestyle intervention proven to be beneficial in several health conditions. Aim: To study the efficacy of 1 week of residential IAYT intervention on cardiovascular parameters in hypertensive patients. METHODOLOGY: Twenty hypertensive individuals (7 females) within age range between 30 and 60 years (average; 46.62 ± 9.9 years), who underwent 1 week of IAYT treatment for HTN, were compared with age- gender-matched non-IAYT group (5 females; average age; 47.08 ± 9.69 years) in terms of systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), cardiac output (CO), stroke volume (SV), baroreflex sensitivity (BRS), and total peripheral vascular resistance (TPVR), IAYT program consisted of sessions of asanas, breathing practices, meditation and relaxation techniques, low salt, low-calorie diet, devotional session, and counseling. Individuals in non-IAYT group followed their normal routine. All the variables were assessed before and after one week. Data were analyzed using SPSS version 16. RM-ANOVA was applied to assess within group and between group changes after intervention. RESULTS: There was a significant improvement in SBP (P = 0.004), DBP (P = 0.008), MAP (0.03), BRS (P < 0.001), and TPVR (P = 0.007) in IAYT, group whereas in control group, we did not find significant difference in any of the variables. Between-group comparison showed a significant improvement in SBP (P = 0.038), BRS (P = 0.034), and TPVR (P = 0.015) in IAYT group as compared to non-IAYT group. CONCLUSION: One-week IAYT intervention showed an improvement in baroreflex sensitivity, systolic BP, and total peripheral vascular resistance in hypertensive patients. However, further randomized control trials need to be performed to confirm the present findings.