Biomarkers of Brain Dysfunction in Perinatal Iron Deficiency.

Iron deficiency in the fetal and neonatal period (perinatal iron deficiency) bodes poorly for neurodevelopment. Given its common occurrence and the negative impact on brain development, a screening and treatment strategy that is focused on optimizing brain development in perinatal iron deficiency is necessary. Pediatric societies currently recommend a universal iron supplementation strategy for full-term and preterm infants that does not consider individual variation in body iron status and thus could lead to undertreatment or overtreatment. Moreover, the focus is on hematological normalcy and not optimal brain development. Several serum iron indices and hematological parameters in the perinatal period are associated with a risk of abnormal neurodevelopment, suggesting their potential use as biomarkers for screening and monitoring treatment in infants at risk for perinatal iron deficiency. A biomarker-based screening and treatment strategy that is focused on optimizing brain development will likely improve outcomes in perinatal iron deficiency.

Anemia, Iron Supplementation, and the Brain.

The developing brain is particularly vulnerable to extrinsic environmental events such as anemia and iron deficiency during periods of rapid development. Studies of infants with postnatal iron deficiency and iron deficiency anemia clearly demonstrated negative effects on short-term and long-term brain development and function. Randomized interventional trials studied erythropoiesis-stimulating agents and hemoglobin-based red blood cell transfusion thresholds to determine how they affect preterm infant neurodevelopment. Studies of red blood cell transfusion components are limited in preterm neonates. A biomarker strategy measuring brain iron status and health in the preanemic period is desirable to evaluate treatment options and brain response.

Iron supplementation and the risk of bronchopulmonary dysplasia in extremely low gestational age newborns.

BACKGROUND: The aim of this study was to determine the relationship between iron exposure and the development of bronchopulmonary dysplasia (BPD). METHODS: A secondary analysis of the PENUT Trial dataset was conducted. The primary outcome was BPD at 36 weeks gestational age and primary exposures of interest were cumulative iron exposures in the first 28 days and through 36 weeks' gestation. Descriptive statistics were calculated for study cohort characteristics with analysis adjusted for the factors used to stratify randomization. RESULTS: Of the 941 patients, 821 (87.2%) survived to BPD evaluation at 36 weeks, with 332 (40.4%) diagnosed with BPD. The median cohort gestational age was 26 weeks and birth weight 810 g. In the first 28 days, 76% of infants received enteral iron and 55% parenteral iron. The median supplemental cumulative enteral and parenteral iron intakes at 28 days were 58.5 and 3.1 mg/kg, respectively, and through 36 weeks' 235.8 and 3.56 mg/kg, respectively. We found lower volume of red blood cell transfusions in the first 28 days after birth and higher enteral iron exposure in the first 28 days after birth to be associated with lower rates of BPD. CONCLUSIONS: We find no support for an increased risk of BPD with iron supplementation. TRIAL REGISTRATION NUMBER: NCT01378273. https://clinicaltrials.gov/ct2/show/NCT01378273 IMPACT: Prior studies and biologic plausibility raise the possibility that iron administration could contribute to the pathophysiology of oxidant-induced lung injury and thus bronchopulmonary dysplasia in preterm infants. For 24-27-week premature infants, this study finds no association between total cumulative enteral iron supplementation at either 28-day or 36-week postmenstrual age and the risk for developing bronchopulmonary dysplasia.

Female and male C57BL/6J offspring exposed to maternal obesogenic diet develop altered hypothalamic energy metabolism in adulthood.

Maternal obesity is exceedingly common and strongly linked to offspring obesity and metabolic disease. Hypothalamic function is critical to obesity development. Hypothalamic mechanisms causing obesity following exposure to maternal obesity have not been elucidated. Therefore, we studied a cohort of C57BL/6J dams, treated with a control or high-fat-high-sugar diet, and their adult offspring to explore potential hypothalamic mechanisms to explain the link between maternal and offspring obesity. Dams treated with obesogenic diet were heavier with mild insulin resistance, which is reflective of the most common metabolic disease in pregnancy. Adult offspring exposed to maternal obesogenic diet had no change in body weight but significant increase in fat mass, decreased glucose tolerance, decreased insulin sensitivity, elevated plasma leptin, and elevated plasma thyroid-stimulating hormone. In addition, offspring exposed to maternal obesity had decreased energy intake and activity without change in basal metabolic rate. Hypothalamic neurochemical profile and transcriptome demonstrated decreased neuronal activity and inhibition of oxidative phosphorylation. Collectively, these results indicate that maternal obesity without diabetes is associated with adiposity and decreased hypothalamic energy production in offspring. We hypothesize that altered hypothalamic function significantly contributes to obesity development. Future studies focused on neuroprotective strategies aimed to improve hypothalamic function may decrease obesity development.NEW & NOTEWORTHY Offspring exposed to maternal diet-induced obesity demonstrate a phenotype consistent with energy excess. Contrary to previous studies, the observed energy phenotype was not associated with hyperphagia or decreased basal metabolic rate but rather decreased hypothalamic neuronal activity and energy production. This was supported by neurochemical changes in the hypothalamus as well as inhibition of hypothalamic oxidative phosphorylation pathway. These results highlight the potential for neuroprotective interventions in the prevention of obesity with fetal origins.

Health-Related Quality of Life Outcomes With Regular Yoga and Heartfulness Meditation Practice: Results From a Multinational, Cross-sectional Study.

BACKGROUND: Although the benefits of yoga are well established across the world, there are limited studies exploring the long-term interrelation between yoga, meditation, and health. Specifically, there is limited research exploring the differences in health-related quality of life (HRQOL) among regular meditators and nonmeditators. OBJECTIVE: This study explored the differences in 7 domains of HRQOL (including quality of life, ability to adopt a healthy lifestyle, ability to relax, frequency of nervousness and stress, coping with day-to-day stress, workplace productivity, and staying healthy during the COVID-19 pandemic) among practitioners of yoga and meditation. METHODS: A cross-sectional, online survey was distributed to all members who participated in a 100-day yoga and meditation program, culminating in the International Day of Yoga event, organized by the Heartfulness Institute in partnership with the Central Council for Research in Yoga and Naturopathy, Ministry of Ayush, SVYASA Yoga University, and Patanjali Yoga Institute, India. The program consisted of daily virtual yoga, meditation, and speaker sessions. The data were analyzed by nonparametric Mann-Whitney U test and Kruskal-Wallis tests for continuous variables and chi-square test for categorical variables. RESULTS: A total of 3164 participants from 39 countries completed the survey. Mean age was 33.8 (SD 13.6) years. The majority of the participants were female (n=1643, 52%) and students (n=1312, 41.5%). Regular yoga and meditation practice was associated with a positive impact on all 7 domains of HRQOL (Mann-Whitney P<.05 and χ2P<.05). Notably, experienced Heartfulness (≥2 years) meditators reported better outcomes in all the domains of HRQOL as compared to those not currently practicing this form of meditation and participants with ≤1 year of Heartfulness meditation experience (P<.05). CONCLUSIONS: This is one of the first cross-sectional studies to explore HRQOL outcomes among participants of a 100-day virtual yoga and meditation program. Overall, a yoga and meditation practice was found to be an effective tool for promoting HRQOL. Regular yoga and meditation practice was associated with factors promoting health and well-being, with long-term meditation practice associated with increased benefits.

Effects of an Integrated Yoga Program on Quality of Life, Spinal Flexibility, and Strength in Older Adults: A Randomized Control Trial.

Context: Aging can contribute to a decrease in physical activity as a result of metabolic dysfunction and hormonal imbalance that can cause degenerative joint disease and aging-related inflammation. As age advances, a decrease in muscle mass, muscle strength, and flexibility can impair physical function. Objective: The study intended to evaluate the effects of an integrated yoga module in improving the flexibility, muscle strength, and quality of life (QOL) of older adults. Design: This research team designed a prospective, two-arm, open-label, and parallel, randomized controlled trial. Setting: The study took place in an outpatient department at Divine Park, Yoga & Naturopathy Hospital, Udupi, Karnataka, India. Participants: Participants were 96 older adults, aged 60-75 years (64.1 ± 3.95 years) taking part in a yoga program in the department. Intervention: The program was a three-month, yoga-based lifestyle intervention. The participants were randomly allocated to the intervention group (n = 48) or to a waitlisted control group (n = 48). The intervention group underwent three one-hour sessions of yoga weekly, with each session including loosening exercises, asanas, pranayama, and meditation spanning. Outcome Measures: At baseline and post intervention, assessments were made: (1) for spinal flexibility using a sit and reach test, (2) for back and leg strength using a back leg dynamometer, (3) for handgrip strength (HGS) and endurance (HGE) using a hand-grip dynamometer, and (4) the Older People's Quality of Life (OPQOL) questionnaire. Analysis was performed employing Wilcoxon's Sign Rank tests and Mann Whitney Tests, using an intention-to-treat approach. Results: Compared to the control group, the intervention group experienced a significantly greater increase in spinal flexibility (P < .001), back leg strength (P < .001), HGE (P < .01), and QOL (P < .001) after three months of yoga. Conclusion: Yoga can be used safely for older adults to improve flexibility, strength, and functional QOL. Larger randomized controlled trials with an active control intervention are warranted.

Enteral Iron Supplementation in Infants Born Extremely Preterm and its Positive Correlation with Neurodevelopment; Post Hoc Analysis of the Preterm Erythropoietin Neuroprotection Trial Randomized Controlled Trial.

OBJECTIVES: To test whether an increased iron dose is associated with improved neurodevelopment as assessed by the Bayley Scales of Infant Development, third edition (BSID-III) among infants enrolled in the Preterm Erythropoietin (Epo) Neuroprotection Trial (PENUT). STUDY DESIGN: This is a post hoc analysis of a randomized trial that enrolled infants born at 24-28 completed weeks of gestation. All infants in PENUT who were assessed with BSID-III at 2 years were included in this study. The associations between enteral iron dose at 60 and 90 days and BSID-III component scores were evaluated using generalized estimating equations models adjusted for potential confounders. RESULTS: In total, 692 infants were analyzed (355 placebo, 337 Epo). Enteral iron supplementation ranged from 0 to 14.7 mg/kg/d (IQR 2.1-5.8 mg/kg/d) at day 60, with a mean of 3.6 mg/kg/d in infants treated with placebo and 4.8 mg/kg/d in infants treated with Epo. A significant positive association was seen between BSID-III cognitive scores and iron dose at 60 days, with an effect size of 0.77 BSID points per 50 mg/kg increase in cumulative iron dose (P = .03). Greater iron doses were associated with greater motor and language scores but did not reach statistical significance. Results at 90 days were not significant. The effect size in the infants treated with Epo compared with placebo was consistently greater. CONCLUSIONS: A positive association was seen between iron dose at 60 days and cognitive outcomes. Our results suggest that increased iron supplementation in infants born preterm, at the doses administered in the PENUT Trial, may have positive neurodevelopmental effects, particularly in infants treated with Epo. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01378273.

Infantile Iron Deficiency Affects Brain Development in Monkeys Even After Treatment of Anemia.

A high percent of oxidative energy metabolism is needed to support brain growth during infancy. Unhealthy diets and limited nutrition, as well as other environmental insults, can compromise these essential developmental processes. In particular, iron deficiency anemia (IDA) has been found to undermine both normal brain growth and neurobehavioral development. Even moderate ID may affect neural maturation because when iron is limited, it is prioritized first to red blood cells over the brain. A primate model was used to investigate the neural effects of a transient ID and if deficits would persist after iron treatment. The large size and postnatal growth of the monkey brain makes the findings relevant to the metabolic and iron needs of human infants, and initiating treatment upon diagnosis of anemia reflects clinical practice. Specifically, this analysis determined whether brain maturation would still be compromised at 1 year of age if an anemic infant was treated promptly once diagnosed. The hematology and iron status of 41 infant rhesus monkeys was screened at 2-month intervals. Fifteen became ID; 12 met clinical criteria for anemia and were administered iron dextran and B vitamins for 1-2 months. MRI scans were acquired at 1 year. The volumetric and diffusion tensor imaging (DTI) measures from the ID infants were compared with monkeys who remained continuously iron sufficient (IS). A prior history of ID was associated with smaller total brain volumes, driven primarily by significantly less total gray matter (GM) and smaller GM volumes in several cortical regions. At the macrostructual level, the effect on white matter volumes (WM) was not as overt. However, DTI analyses of WM microstructure indicated two later-maturating anterior tracts were negatively affected. The findings reaffirm the importance of iron for normal brain development. Given that brain differences were still evident even after iron treatment and following recovery of iron-dependent hematological indices, the results highlight the importance of early detection and preemptive supplementation to limit the neural consequences of ID.

Effect of iron supplementation from neonatal period on the iron status of6-month-old infants at-risk for early iron deficiency: a randomized interventional trial.

OBJECTIVE: To investigate the effects of iron supplementation from the second day after birth on 6-month hemoglobin (Hb), serum ferritin and motor development in infants at risk of early iron deficiency. STUDY DESIGN: Term (37-41 weeks) infants of anemic (Hb ≤ 100 g L-1; N = 100) and non-anemic (Hb > 100 g L-1; N = 100) mothers were randomized to daily iron supplementation at a dose of 2 mg kg-1 from 36 h of age (N = 50, each of anemic and non-anemic mothers) or no iron-supplementation (N = 50 each of anemic and non-anemic mothers). Hb, serum ferritin and motor development at 6 months were compared in the two groups. RESULTS: Iron-supplemented infants had higher Hb (103.7 ± 9.3 g L-1 versus 97.0 ± 9.4 g L-1, p < .0001) and serum ferritin (133.93 ± 52.41 ng mL-1 versus 78.09 ± 42.03 ng mL-1, p < .001) concentrations, compared with the no iron-supplementation group. Their motor development was closer to age-appropriate norms than the no iron-supplementation group (5.83 ± 0.69 versus 5.18 ± 1.35, p < .01). CONCLUSION: Early Iron supplementation is effective for improving iron status and motor development at 6 months in infants at risk for early iron deficiency.

Comparison of Intravascular Ultrasound Virtual Histology Parameters in Diabetes versus Non-Diabetes with Acute Coronary Syndrome.

INTRODUCTION: The progression and pattern of coronary atherosclerosis in diabetes mellitus (DM) is different from non-DM, leading to a higher rate of vascular complications in DM. OBJECTIVE: This study aims to assess and compare the high-risk plaque characteristics in the culprit artery of DM and non-DM patients with acute coronary syndrome (ACS) using virtual histology intravascular ultrasound (VH-IVUS). METHODS: A total of 158 ACS patients were included, 63 of whom were known to have DM. IVUS analysis was done in the de novo target vessel and culprit lesion for which percutaneous coronary intervention was planned. Culprit lesions with a visual-estimate angiographic stenosis of <70% were excluded. RESULTS: The mean age of patients was 52.4 ± 11.6 years. The study group comprised 82% men, 31% with hypertension, and 39.87% with DM. No significant difference was observed between the DM and non-DM groups in relation to quantitative IVUS parameters like lesion length, minimal lumen area, and plaque area. However, there was a significant difference in VH-IVUS parameters like higher necrotic core and dense calcium in the DM patients than in the non-DM patients (p < 0.01). The occurrence of VH-derived thin-cap fibroatheroma (VH-TCFA) in the culprit vessel was significantly higher in the DM group than in the non-DM group (25.3 vs. 5.2%; p < 0.01). Positive vessel-wall remodeling was noted in both groups without any significant difference (p = 0.74). CONCLUSION: The DM patients had high-risk plaque composition features like a higher necrotic core, which is a marker of plaque vulnerability. Thus, aggressive medical therapy targeting vascular inflammation using high-dose statins would help in the stabilization of unstable plaque morphology and the reduction of major cardiovascular events.

Effects of Iron Deficiency Anemia and Its Rapid Correction on the Serum Metabolomic Profile of Rhesus Infants.

OBJECTIVES: To determine whether rapid correction of iron deficiency using intramuscular iron dextran normalizes serum metabolomic changes in a nonhuman primate model of iron deficiency anemia (IDA). METHODS: Blood was collected from naturally iron-sufficient (IS; n = 10) and IDA (n = 12) male and female infant rhesus monkeys (Macaca mulatta) at 6 months of age. IDA infants were treated with intramuscular injections of iron dextran, 10 mg/weekly for 4-8 weeks. Iron status was reevaluated following treatment using hematological measurements and sera were metabolically profiled using HPLC/MS with isobaric standards for identification and quantification. RESULTS: Early-life iron deficiency anemia negatively affects many cellular metabolic processes, including energy production, electron transport, and oxidative degradation of toxins. Slow iron repletion with dietary supplementation restores iron deficient monkeys from a hematological perspective, but the serum metabolomic profile remains differed from monkeys that had been iron sufficient their entire life. Whether rapid iron restoration through intramuscular injections of iron dextran normalizes serum metabolomic profile is not known. A total of 654 metabolites were measured with differences in 53 metabolites identified between IS and IDA monkeys at 6 months (P 0.05). Pathway analyses provided evidence of altered liver function, hypometabolic state, differential essential fatty acid production, irregular inosine and guanosine metabolism, and atypical bile acid production in IDA infants. After treatment, iron-related hematological parameters had recovered, but the formerly IDA infants remained metabolically distinct from the IS infants, with 225 metabolites differentially expressed between the groups. CONCLUSIONS: As with slow iron repletion, rapid iron repletion does not normalize the altered serum metabolomic profile in rhesus infants with IDA, suggesting the need for iron supplementation in the pre-anemic stage. FUNDING SOURCES: National Institutes of Health.

High Prevalence of Iron Deficiency Despite Standardized High-Dose Iron Supplementation During Recombinant Erythropoietin Therapy in Extremely Low Gestational Age Newborns.

OBJECTIVE: To assess the effects of protocolized recombinant human erythropoietin (r-HuEPO) therapy and standardized high dose iron supplementation on hematologic and iron status measures in a cohort of extremely low gestational age newborns (ELGANs). STUDY DESIGN: Charts of extremely low gestational age newborns admitted from 2006 to 2016 and who had received r-HuEPO per neonatal intensive care unit protocol were reviewed. The r-HuEPO was started at a dose of 900 IU/kg per week after 7 days of age and continued until 35 weeks postmenstrual age. Oral iron supplementation at 6-12 mg/kg per day was used to maintain a transferrin saturation of >20% during r-HuEPO treatment. Data on demographic features, hematologic and iron panel indices, red blood cell transfusions, and clinical outcomes were collected. Quartile groups were created based on serum ferritin levels at the conclusion of the r-HuEPO treatment and the quartiles were compared. RESULTS: The cohort included 116 infants with mean gestational age 25.8 ± 1.5 weeks and birth weight 793 ± 174.1 g. The r-HuEPO promoted erythropoiesis as indicated by increasing hemoglobin, hematocrit, and reticulocyte count. Serum ferritin decreased over time and was ≤75 ng/mL in 60.2% of infants at the conclusion of r-HuEPO therapy; 87% received packed red blood cell transfusions. Transfusion volume, total iron intake, total iron binding capacity, and transferrin concentration differed among infants in the different serum ferritin quartiles (P < .05). CONCLUSIONS: In extremely low gestational age newborns, r-HuEPO therapy promoted erythropoiesis. Despite a biomarker-based standardized high-dose iron supplementation, the majority of infants had evidence of iron deficiency to a degree that is associated with reduced brain function.

Using an integrated teaching approach to facilitate student achievement of the learning outcomes in a preclinical medical curriculum in India.

Today most education institutions around the world have adopted the philosophy of outcome-based education. The emphasis in outcome-based education is achievement of outcomes; hence the curriculum should be designed in a way that it includes the components targeted specifically at achieving these outcomes. A discipline-based approach results in fragmentation of learning and lack of clinical applicability. Integrated teaching could be a solution to achieve required outcomes in a holistic way. Hence, the aim of this study was to develop, implement, and evaluate an integrated teaching module. Temporal coordination of the basic sciences, along with correlation of learned topics to clinical settings, was done in the first year of the undergraduate medical program. The module was evaluated by obtaining qualitative and quantitative feedback from students. Student assessment was conducted with a test that had case vignettes and multiple-choice questions. In addition, students' change in learning approaches and self-directed learning readiness were collected. Students' perception regarding the educational environment was also obtained. Analysis of the data showed positive feedback from the students regarding the integrated teaching. Students' average score in the test was 86%. There was a significant increase in the scores for the deep approach and self-directed learning readiness in the posttest compared with the pretest. Moreover, students were found to be satisfied with the educational environment. Evaluation of integrated teaching revealed that it was well accepted by the students. Moreover, it facilitated the achievement of the students' outcomes.

Approaches for Reducing the Risk of Early-Life Iron Deficiency-Induced Brain Dysfunction in Children.

Iron deficiency is the most common micronutrient deficiency in the world. Women of reproductive age and young children are particularly vulnerable. Iron deficiency in late prenatal and early postnatal periods can lead to long-term neurobehavioral deficits, despite iron treatment. This may occur because screening and treatment of iron deficiency in children is currently focused on detection of anemia and not neurodevelopment. Anemia is the end-stage state of iron deficiency. The brain becomes iron deficient before the onset of anemia due to prioritization of the available iron to the red blood cells (RBCs) over other organs. Brain iron deficiency, independent of anemia, is responsible for the adverse neurological effects. Early diagnosis and treatment of impending brain dysfunction in the pre-anemic stage is necessary to prevent neurological deficits. The currently available hematological indices are not sensitive biomarkers of brain iron deficiency and dysfunction. Studies in non-human primate models suggest that serum proteomic and metabolomic analyses may be superior for this purpose. Maternal iron supplementation, delayed clamping or milking of the umbilical cord, and early iron supplementation improve the iron status of at-risk infants. Whether these strategies prevent iron deficiency-induced brain dysfunction has yet to be determined. The potential for oxidant stress, altered gastrointestinal microbiome and other adverse effects associated with iron supplementation cautions against indiscriminate iron supplementation of children in malaria-endemic regions and iron-sufficient populations.

Effect of Long-term Yoga Practice on Psychological outcomes in Breast Cancer Survivors.

AIM: Breast cancer has become a pandemic with an ever-increasing incidence. Although better diagnostics and treatment modalities have reduced mortality, a large number of survivors face cancer and treatment-related long-term symptoms. Many survivors are taking up yoga for improving the quality of life (QoL). The present study attempts to evaluate predictors of psychological states in breast cancer survivors with long-term yoga experience. MATERIALS AND METHODS: A case-control study recruited early breast cancer survivors, 30-65 years, completing treatment > 6 months before recruitment, and grouped them based on prior yoga experience (BCY, n = 27) or naïve (BCN, n = 25). Demography, cancer history, diet, exercise habits, and yoga schedule were collected and tools to assess stress, anxiety, depression, general health, and QoL were administered. Multivariate linear regression was done to identify predictors of psychological variables. RESULTS: BCY had significantly lower stress, anxiety, depression, better general health, and QoL (P < 0.001). Global QoL and trait anxiety were significantly predicted by Yoga practice; depression was predicted by yoga practice, annual income, and sleep quality; state anxiety was predicted by Yoga practice and income; and stress was predicted by Yoga practice and sleep quality. CONCLUSION: Results indicate that breast cancer survivors, doing yoga, have better psychological profiles and are able to deal with demanding situations better. The psycho-oncogenic model of cancer etiology suggests that a better psychological state in survival has the potential to improve prognosis and survival outcomes and Yoga may be a suitable practice for staying cancer-free for a longer time.

Effects of Yoga in Managing Fatigue in Breast Cancer Patients: A Randomized Controlled Trial.

BACKGROUND: Cancer-related fatigue is widely prevalent in cancer patients and affects quality of life in advanced cancer patients. Fatigue is caused due to both psychologic distress and physiological sequel following cancer progression and its treatment. In this study, we evaluate the effects of yogic intervention in managing fatigue in metastatic breast cancer patients. METHODS: Ninety-one patients with metastatic breast cancer were randomized to receive integrated yoga program (n = 46) or supportive therapy and education (n = 45) over a 3-month period. Assessments such as perceived stress, fatigue symptom inventory, diurnal salivary cortisol, and natural killer cell counts were carried out before and after intervention. Analysis was done using an intention-to-treat approach. Postmeasures for the above outcomes were assessed using ANCOVA with respective baseline measure as a covariate. RESULTS: The results suggest that yoga reduces perceived stress (P = 0.001), fatigue frequency (P < 0.001), fatigue severity (P < 0.001), interference (P < 0.001), and diurnal variation (P < 0.001) when compared to supportive therapy. There was a positive correlation of change in fatigue severity with 9 a.m. salivary cortisol levels. CONCLUSION: The results suggest that yoga reduces fatigue in advanced breast cancer patients.

Effect of Yoga on Sleep Quality and Neuroendocrine Immune Response in Metastatic Breast Cancer Patients.

BACKGROUND: Studies have shown that distress and accompanying neuroendocrine stress responses as important predictor of survival in advanced breast cancer patients. Some psychotherapeutic intervention studies have shown have modulation of neuroendocrine-immune responses in advanced breast cancer patients. In this study, we evaluate the effects of yoga on perceived stress, sleep, diurnal cortisol, and natural killer (NK) cell counts in patients with metastatic cancer. METHODS: In this study, 91 patients with metastatic breast cancer who satisfied selection criteria and consented to participate were recruited and randomized to receive "integrated yoga based stress reduction program" (n = 45) or standard "education and supportive therapy sessions" (n = 46) over a 3 month period. Psychometric assessments for sleep quality were done before and after intervention. Blood draws for NK cell counts were collected before and after the intervention. Saliva samples were collected for three consecutive days before and after intervention. Data were analyzed using the analysis of covariance on postmeasures using respective baseline measure as a covariate. RESULTS: There was a significant decrease in scales of symptom distress (P < 0.001), sleep parameters (P = 0.02), and improvement in quality of sleep (P = 0.001) and Insomnia Rating Scale sleep score (P = 0.001) following intervention. There was a decrease in morning waking cortisol in yoga group (P = 0.003) alone following intervention. There was a significant improvement in NK cell percent (P = 0.03) following intervention in yoga group compared to control group. CONCLUSION: The results suggest modulation of neuroendocrine responses and improvement in sleep in patients with advanced breast cancer following yoga intervention.

Role of Yoga in Cancer Patients: Expectations, Benefits, and Risks: A Review.

BACKGROUND: The diagnosis and treatment of cancer poses severe psychologic distress that impacts functional quality of life. While cancer directed treatments are directed purely against tumor killing, interventions that reduce treatment related distress and improve quality of life are the need of the hour. Yoga is one such mind body intervention that is gaining popularity among cancer patients. METHOD: Several research studies in the last two decades unravel the benefits of yoga in terms of improved mood states, symptom reduction, stress reduction and improved quality of life apart from improving host factors that are known to affect survival in cancer patients. However, several metaanalysis and reviews show equivocal benefits for yoga. In this review, we will study the Yoga interventions in cancer patients with respect to expectations, benefits and risks and analyse the principles behind tailoring yoga interventions in cancer patients. RESULTS: The studies on Yoga show heterogeneity with varied types of Yoga Interventions, duration, exposure, practices and indications. It also elucidates the situational context for reaping benefits and cautions against its use in several others. However, there are several reviews and bibliometric analysis of effects of yoga; most of them have not enlarged the scope of their review to cover the basic principles behind use of these practices in cancer patients. CONCLUSION: This review offers insight into the principles and practice of yoga in cancer patients.

Effects of a Yoga Program on Mood States, Quality of Life, and Toxicity in Breast Cancer Patients Receiving Conventional Treatment: A Randomized Controlled Trial.

AIMS: The aim of this study is to compare the effects of yoga program with supportive therapy counseling on mood states, treatment-related symptoms, toxicity, and quality of life in Stage II and III breast cancer patients on conventional treatment. METHODS: Ninety-eight Stage II and III breast cancer patients underwent surgery followed by adjuvant radiotherapy (RT) or chemotherapy (CT) or both at a cancer center were randomly assigned to receive yoga (n = 45) and supportive therapy counseling (n = 53) over a 24-week period. Intervention consisted of 60-min yoga sessions, daily while the control group was imparted supportive therapy during their hospital visits. Assessments included state-trait anxiety inventory, Beck's depression inventory, symptom checklist, common toxicity criteria, and functional living index-cancer. Assessments were done at baseline, after surgery, before, during, and after RT and six cycles of CT. RESULTS: Both groups had similar baseline scores. There were 29 dropouts 12 (yoga) and 17 (controls) following surgery. Sixty-nine participants contributed data to the current analysis (33 in yoga, and 36 in controls). An ANCOVA, adjusting for baseline differences, showed a significant decrease for the yoga intervention as compared to the control group during RT (first result) and CT (second result), in (i) anxiety state by 4.72 and 7.7 points, (ii) depression by 5.74 and 7.25 points, (iii) treatment-related symptoms by 2.34 and 2.97 points, (iv) severity of symptoms by 6.43 and 8.83 points, (v) distress by 7.19 and 13.11 points, and (vi) and improved overall quality of life by 23.9 and 31.2 points as compared to controls. Toxicity was significantly less in the yoga group (P = 0.01) during CT. CONCLUSION: The results suggest a possible use for yoga as a psychotherapeutic intervention in breast cancer patients undergoing conventional treatment.

Recurrent Moderate Hypoglycemia Suppresses Brain-Derived Neurotrophic Factor Expression in the Prefrontal Cortex and Impairs Sensorimotor Gating in the Posthypoglycemic Period in Young Rats.

Recurrent hypoglycemia is common in infants and children. In developing rat models, recurrent moderate hypoglycemia leads to neuronal injury in the medial prefrontal cortex. To understand the effects beyond neuronal injury, 3-week-old male rats were subjected to 5 episodes of moderate hypoglycemia (blood glucose concentration, approx. 30 mg/dl for 90 min) once daily from postnatal day 24 to 28. Neuronal injury was determined using Fluoro-Jade B histochemistry on postnatal day 29. The effects on brain-derived neurotrophic factor (BDNF) and its cognate receptor, tyrosine kinase receptor B (TrkB) expression, which is critical for prefrontal cortex development, were determined on postnatal day 29 and at adulthood. The effects on prefrontal cortex-mediated function were determined by assessing the prepulse inhibition of the acoustic startle reflex on postnatal day 29 and 2 weeks later, and by testing for fear-potentiated startle at adulthood. Recurrent hypoglycemia led to neuronal injury confined primarily to the medial prefrontal cortex. BDNF/TrkB expression in the prefrontal cortex was suppressed on postnatal day 29 and was accompanied by lower prepulse inhibition, suggesting impaired sensorimotor gating. Following the cessation of recurrent hypoglycemia, the prepulse inhibition had recovered at 2 weeks. BDNF/TrkB expression in the prefrontal cortex had normalized and fear-potentiated startle was intact at adulthood. Recurrent moderate hypoglycemia during development has significant adverse effects on the prefrontal cortex in the posthypoglycemic period.