Effects of Acute and Repeated Dose Toxicity Profiling of Chelidonic Acid in Rats: in Silico and in Vivo Evidence.

Chelidonic acid is a phytoconstituent found in rhizomes of the perennial plant celandine. The current study aims to evaluate the acute and repeated dose oral toxicity study of chelidonic acid as per the OECD guidelines 425 and 407. The pharmacokinetic and toxicity profile of chelidonic acid was predicted using online servers and tools. A single dose of chelidonic acid (2000 mg/kg) was administered to female Wistar rats in an acute toxicity study, and the animals were monitored for 14 days. We studied the toxicity profile of chelidonic acid at 10, 20, and 40 mg/kg doses in Wistar rats for repeated dose toxicity (28 days). Clinical biochemistry, haematological, and urine parameters were estimated. A gross necropsy and histopathology were performed. A single oral dose of chelidonic acid (2000 mg/kg) showed no signs of toxicity or mortality. The Administration of chelidonic acid showed no significant alterations in haematological, biochemical, and urine parameters. The histopathology showed normal structure and architecture in all the vital organs. A gross necropsy of vital organs showed no signs of toxicity. The chelidonic acid was found to be safe at all selected dose levels in the acute and repeated dose toxicity study in rats.

Therapeutic Management and New Upcoming Approaches for Age Related Macular Degeneration.

Age-related Macular Degeneration (AMD) is a severe eye illness that is going to lead in the race for incurable blindness globally among the elderly population. AMD is the third common reason responsible for affecting the quality of life globally. The macula and the retinal layers are adversely affected during AMD and are responsible for the loss of vision eventually. Numerous genetic variables, lipid metabolism, ageing and oxidative damage are the causative factors in the genesis of AMD. Lack of antioxidants, smoking and excessive alcohol intake contribute to increasing the risk of AMD. Management of dry AMD involves the use of nutritional supplements like zinc and antioxidants, along with conventional treatment, however, the use of nutritional supplements can only give minor benefits on the progression of dry AMD. Later stages of AMD need to be managed by cell-based interventions where the damaged or lost cells are replaced with fresh donor cells. A plethora of treatment methods are used in the management of AMD, such as nutrition, antibody-based treatments, stem cell management and nanotherapeutics. The available expensive treatments come with a number of adverse effects and future developments require the involvement of risk factor modification approaches, personalized therapy, targeting the disease specific pathways, exploring better anti-vascular endothelial growth factor (VEGF) inhibitors and many other regenerative approaches, that will broaden techniques to diagnose, control and treat AMD. This review provides an overview of the progression of AMD and the causative factors, with considerable emphasises on the current and potential prospects.

Characterizing variability in total mercury hair:blood ratio in the general Canadian population.

BACKGROUND/OBJECTIVES: The body burden of mercury in humans can be measured through hair or blood biomarkers. To compare results from different studies, it is often required to convert mercury in hair to an equivalent level in blood, using a default hair:blood ratio of 250:1 by the World Health Organization (WHO). However, the actual ratio may vary within and between populations. The objectives of this study were to analyze the hair:blood mercury ratio in the general Canadian population, explore factors associated with higher/lower ratios, and determine if the standard ratio of 250:1 is supported. METHODS: The Canadian Health Measures Survey (CHMS) Cycle 5 (2016-2017) measured total mercury (THg) in both hair and blood of 1168 participants 20-59 years of age. We calculated geometric mean (GM) concentrations of THg for this entire sample and subgroups. The subgroups included biological sex, women of childbearing age, race, hair treatments, categories of blood and hair selenium, urinary arsenobetaine/arsenocholine, categories of blood and hair mercury, and food consumption. We calculated a hair:blood ratio for each participant and determined population-level ratios from the GMs of the distributions. Differences by subgroups, and agreement with the WHO ratio of 250:1, were tested. The combined effect of factors on the THg hair:blood ratio was explored using staged regression analysis. RESULTS: For participants with paired hair and blood mercury measurements, the GM of the hair:blood THg ratio was 293 (95%CI:273-316), and significantly >250. In women of childbearing age, the ratio did not differ from 250. The GMs of the ratio were higher (i.e.>300) for second tertile blood selenium (365, 95%CI:307-433), third and fourth quartiles hair mercury (347, 95%CI:308-390 and 376, 95%CI:336-422), and consumers of shellfish (338, 95%CI:308-371). Shellfish consumption was the only statistically significant factor associated with the hair:blood ratio as identified in the regression model. CONCLUSIONS: The mean hair:blood THg ratio among Canadians generally exceeded the default ratio of 250:1. Higher ratios were observed in certain subgroups, such as seafood consumers, and shellfish consumption was the most important variable associated with the ratio. Our results suggest that population-specific hair:blood THg ratios be considered, if possible, when converting mercury levels from hair to blood to better characterize the variation around the conversion.

Cardiotoxicity linked to anticancer agents and cardioprotective strategy.

Chemotherapy is a main treatment for cancer, and it benefits patients by controlling cancer relapse and metastasis, thereby leading to an increase in the overall survival rate. However, this treatment is associated with mild to severe side effects, one of which is cardiotoxicity. The severity of cardiotoxicity, a leading cause of cardiovascular diseases, depends on the type of cancer therapy employed and the time required for its management. A chemotherapeutic agent is used either alone or in combination with other drugs for cancer treatment. The exact mechanism of chemotherapeutic agent-induced cardiotoxicity remains unclear, although it is likely to be multifactorial and to include oxidative stress, apoptosis, and inflammation. There are many approaches to avoid the untoward effects of chemotherapeutic agents. However, the available options for cardiac protection are minimal, and they include renin-angiotensin system blockers, beta-blockers, herbal drugs, or iron chelators such as dexrazoxane. The present review provides information on the molecular mechanism of chemotherapy-induced myocardial infarction and cardiotoxicity along with scientifically studied synthetic molecules, herbal extracts, and natural products to manage chemotherapy-induced cardiotoxicity.

Feasibility Trial of Yoga Programme for Type 2 Diabetes Prevention (YOGA-DP) among High-Risk People in India: A Qualitative Study to Explore Participants' Trial- and Intervention-Related Barriers and Facilitators.

Yoga-based interventions can be effective in preventing type 2 diabetes mellitus (T2DM). We developed a Yoga programme for T2DM prevention (YOGA-DP) and conducted a feasibility randomised controlled trial (RCT) among high-risk people in India. This qualitative study's objective was to identify and explore participants' trial- and intervention-related barriers and facilitators. The feasibility trial was conducted at two Yoga centres in New Delhi and Bengaluru, India. In this qualitative study, 25 trial participants (13 intervention group, 12 control group) were recruited for semi-structured interviews. Data were analysed using deductive logic and an interpretative phenomenological approach. Amongst intervention and control participants, key barriers to trial participation were inadequate information about recruitment and randomisation processes and the negative influence of non-participants. Free blood tests to aid T2DM prevention, site staff's friendly behaviour and friends' positive influence facilitated trial participation. Amongst intervention participants, readability and understanding of the programme booklets, dislike of the Yoga diary, poor quality Yoga mats, difficulty in using the programme video, household commitment during home sessions, unplanned travel, difficulty in practising Yoga poses, hesitation in attending programme sessions with the YOGA-DP instructor of the opposite sex and mixed-sex group programme sessions were key barriers to intervention participation. Adequate information was provided on T2DM prevention and self-care, good venue and other support provided for programme sessions, YOGA-DP instructors' positive behaviour and improvements in physical and mental well-being facilitated intervention participation. In conclusion, we identified and explored participants' trial- and intervention-related barriers and facilitators. We identified an almost equal number of barriers (n = 12) and facilitators (n = 13); however, intervention-related barriers and facilitators were greater than for participating in the trial. These findings will inform the design of the planned definitive RCT design and intervention and can also be used to design other Yoga interventions and RCTs.

Functional connectome of arousal and motor brainstem nuclei in living humans by 7 Tesla resting-state fMRI.

Brainstem nuclei play a pivotal role in many functions, such as arousal and motor control. Nevertheless, the connectivity of arousal and motor brainstem nuclei is understudied in living humans due to the limited sensitivity and spatial resolution of conventional imaging, and to the lack of atlases of these deep tiny regions of the brain. For a holistic comprehension of sleep, arousal and associated motor processes, we investigated in 20 healthy subjects the resting-state functional connectivity of 18 arousal and motor brainstem nuclei in living humans. To do so, we used high spatial-resolution 7 Tesla resting-state fMRI, as well as a recently developed in-vivo probabilistic atlas of these nuclei in stereotactic space. Further, we verified the translatability of our brainstem connectome approach to conventional (e.g. 3 Tesla) fMRI. Arousal brainstem nuclei displayed high interconnectivity, as well as connectivity to the thalamus, hypothalamus, basal forebrain and frontal cortex, in line with animal studies and as expected for arousal regions. Motor brainstem nuclei showed expected connectivity to the cerebellum, basal ganglia and motor cortex, as well as high interconnectivity. Comparison of 3 Tesla to 7 Tesla connectivity results indicated good translatability of our brainstem connectome approach to conventional fMRI, especially for cortical and subcortical (non-brainstem) targets and to a lesser extent for brainstem targets. The functional connectome of 18 arousal and motor brainstem nuclei with the rest of the brain might provide a better understanding of arousal, sleep and accompanying motor functions in living humans in health and disease.

Yoga Program for Type 2 Diabetes Prevention (YOGA-DP) Among High-Risk People: Qualitative Study to Explore Reasons for Non-participation in a Feasibility Randomized Controlled Trial in India.

Background: Yoga-based interventions can be effective in preventing type 2 diabetes mellitus (T2DM). We developed a Yoga program for T2DM prevention (YOGA-DP) among high-risk people and conducted a feasibility randomized controlled trial (RCT) in India. The objective of this study was to identify and explore why potential participants declined to participate in the feasibility RCT. Methods: An exploratory qualitative study, using semi-structured interviews, was conducted at a Yoga center in New Delhi, India. Fourteen people (10 women and four men) who declined to participate in the feasibility RCT were interviewed, and 13 of them completed the non-participant questionnaire, which captured their socio-demographics, diets, physical activities, and reasons for declining. Results: Three types of barriers were identified and explored which prevented participation in the feasibility RCT: (1) personal barriers, such as lack of time, perceived sufficiency of knowledge, preferences about self-management of health, and trust in other traditional and alternative therapies; (2) contextual barriers, such as social influences and lack of awareness about preventive care; and (3) study-related barriers, such as lack of study information, poor accessibility to the Yoga site, and lack of trust in the study methods and intervention. Conclusions: We identified and explored personal, contextual, and study-related barriers to participation in a feasibility RCT in India. The findings will help to address recruitment challenges in future Yoga and other RCTs. Clinical Trial Registration:www.ClinicalTrials.gov, identifier: CTRI/2019/05/018893.

Development of a Yoga Program for Type-2 Diabetes Prevention (YOGA-DP) Among High-Risk People in India.

Introduction: Many Indians are at high-risk of type-2 diabetes mellitus (T2DM). Yoga is an ancient Indian mind-body discipline, that has been associated with improved glucose levels and can help to prevent T2DM. The study aimed to systematically develop a Yoga program for T2DM prevention (YOGA-DP) among high-risk people in India using a complex intervention development approach. Materials and Methods: As part of the intervention, we developed a booklet and a high-definition video for participants and a manual for YOGA-DP instructors. A systematic iterative process was followed to develop the intervention and included five steps: (i) a systematic review of the literature to generate a list of Yogic practices that improves blood glucose levels among adults at high-risk of or with T2DM, (ii) validation of identified Yogic practices by Yoga experts, (iii) development of the intervention, (iv) consultation with Yoga, exercise, physical activity, diet, behavior change, and/or diabetes experts about the intervention, and (v) pretest the intervention among Yoga practitioners and lay people (those at risk of T2DM and had not practiced Yoga before) in India. Results: YOGA-DP is a structured lifestyle education and exercise program, provided over a period of 24 weeks. The exercise part is based on Yoga and includes Shithilikarana Vyayama (loosening exercises), Surya Namaskar (sun salutation exercises), Asana (Yogic poses), Pranayama (breathing practices), and Dhyana (meditation) and relaxation practices. Once participants complete the program, they are strongly encouraged to maintain a healthy lifestyle in the long-term. Conclusions: We systematically developed a novel Yoga program for T2DM prevention (YOGA-DP) among high-risk people in India. A multi-center feasibility randomized controlled trial is in progress in India.

Yoga programme for type-2 diabetes prevention (YOGA-DP) among high risk people in India: a multicentre feasibility randomised controlled trial protocol.

INTRODUCTION: A huge population in India is at high risk of type-2 diabetes (T2DM). Physical activity and a healthy diet (healthy lifestyle) improve blood glucose levels in people at high risk of T2DM. However, an unhealthy lifestyle is common among Indians. Yoga covers physical activity and a healthy diet and can help to prevent T2DM. The research question to be addressed by the main randomised controlled trial (RCT) is whether a Yoga programme for T2DM prevention (YOGA-DP) is effective in preventing T2DM among high risk people in India as compared with enhanced standard care. In this current study, we are determining the feasibility of undertaking the main RCT. INTERVENTION: YOGA-DP is a structured lifestyle education and exercise programme. The exercise part is based on Yoga and includes Shithilikarana Vyayama (loosening exercises), Surya Namaskar (sun salutation exercises), Asana (Yogic poses), Pranayama (breathing practices) and Dhyana (meditation) and relaxation practices. METHODS AND ANALYSIS: This is a multicentre, two-arm, parallel-group, feasibility RCT with blinded outcome assessment and integrated mixed-methods process evaluation. Eligible participants should be aged 18-74 years, at high risk of T2DM (fasting plasma glucose level 5.6-6.9 mmol/L) and safe to participate in physical activities. At least 64 participants will be randomised to intervention or control group with final follow-up at 6 months. Important parameters, needed to design the main RCT, will be estimated, such as SD of the outcome measure (fasting plasma glucose level at 6-month follow-up), recruitment, intervention adherence, follow-up, potential contamination and time needed to conduct the study. Semistructured qualitative interviews will be conducted with up to 20-30 participants, a sample of those declining to participate, four YOGA-DP instructors and around eight study staff to explore their perceptions and experiences of taking part in the study and of the intervention, reasons behind non-participation, experiences of delivering the intervention and running the study, respectively. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the following Research Ethics Committees: Faculty of Medicine and Health Sciences, University of Nottingham (UK); Centre for Chronic Disease Control (CCDC, India); Bapu Nature Cure Hospital and Yogashram (BNCHY, India) and Swami Vivekananda Yoga Anusandhana Samsthana (S-VYASA, India). The results will be widely disseminated among key stakeholders through various avenues. TRIAL REGISTRATION NUMBER: CTRI/2019/05/018893.

The impacts of quality improvement on maternal and newborn health: preliminary findings from a health system integrated intervention in four Ethiopian regions.

BACKGROUND: Quality improvement (QI) methods are effective in improving healthcare delivery using sustainable, collaborative, and cost-effective approaches. Systems-integrated interventions offer promise in terms of producing sustainable impacts on service quality and coverage, but can also improve important data quality and information systems at scale. METHODS: This study assesses the preliminary impacts of a first phase, quasi-experimental, QI health systems intervention on maternal and neonatal health outcomes in four pilot districts in Ethiopia. The intervention identified, trained, and coached QI teams to develop and test change ideas to improve service delivery. We use an interrupted time-series approach to evaluate intervention effects over 32-months. Facility-level outcome indicators included: proportion of mothers receiving four antenatal care visits, skilled delivery, syphilis testing, early postnatal care, proportion of low birth weight infants, and measures of quality delivery of childbirth services. RESULTS: Following the QI health systems intervention, we found a significant increase in the rate of syphilis testing (ß = 2.41, 95% CI = 0.09,4.73). There were also large positive impacts on health worker adherence to safe child birth practices just after birth (ß = 8.22, 95% CI = 5.15, 11.29). However, there were limited detectable impacts on other facility-usage indicators. Findings indicate early promise of systems-integrated QI on the delivery of maternal health services, and increased some service coverage. CONCLUSIONS: This study preliminarily demonstrates the feasibility of complex, low-cost, health-worker driven improvement interventions that can be adapted in similar settings around the world, though extended follow up time may be required to detect impacts on service coverage. Policy makers and health system workers should carefully consider what these findings mean for scaling QI approaches in Ethiopia and other similar settings.

Yoga-Based Cardiac Rehabilitation After Acute Myocardial Infarction: A Randomized Trial.

BACKGROUND: Given the shortage of cardiac rehabilitation (CR) programs in India and poor uptake worldwide, there is an urgent need to find alternative models of CR that are inexpensive and may offer choice to subgroups with poor uptake (e.g., women and elderly). OBJECTIVES: This study sought to evaluate the effects of yoga-based CR (Yoga-CaRe) on major cardiovascular events and self-rated health in a multicenter randomized controlled trial. METHODS: The trial was conducted in 24 medical centers across India. This study recruited 3,959 patients with acute myocardial infarction with a median and minimum follow-up of 22 and 6 months. Patients were individually randomized to receive either a Yoga-CaRe program (n = 1,970) or enhanced standard care involving educational advice (n = 1,989). The co-primary outcomes were: 1) first occurrence of major adverse cardiovascular events (MACE) (composite of all-cause mortality, myocardial infarction, stroke, or emergency cardiovascular hospitalization); and 2) self-rated health on the European Quality of Life-5 Dimensions-5 Level visual analogue scale at 12 weeks. RESULTS: MACE occurred in 131 (6.7%) patients in the Yoga-CaRe group and 146 (7.4%) patients in the enhanced standard care group (hazard ratio with Yoga-CaRe: 0.90; 95% confidence interval [CI]: 0.71 to 1.15; p = 0.41). Self-rated health was 77 in Yoga-CaRe and 75.7 in the enhanced standard care group (baseline-adjusted mean difference in favor of Yoga-CaRe: 1.5; 95% CI: 0.5 to 2.5; p = 0.002). The Yoga-CaRe group had greater return to pre-infarct activities, but there was no difference in tobacco cessation or medication adherence between the treatment groups (secondary outcomes). CONCLUSIONS: Yoga-CaRe improved self-rated health and return to pre-infarct activities after acute myocardial infarction, but the trial lacked statistical power to show a difference in MACE. Yoga-CaRe may be an option when conventional CR is unavailable or unacceptable to individuals. (A study on effectiveness of YOGA based cardiac rehabilitation programme in India and United Kingdom; CTRI/2012/02/002408).

Development of a Yoga-Based Cardiac Rehabilitation (Yoga-CaRe) Programme for Secondary Prevention of Myocardial Infarction.

Cardiac rehabilitation (CR) after myocardial infarction is highly effective. It is unavailable in public hospitals in India due to limited resources. Our objective was to develop a scalable model of CR for India based on yoga, which could also appeal to some groups with low uptake of CR (e.g., ethnic minorities, women, and older people) globally. The intervention was developed using a structured process. A literature review and consultations with yoga experts, CR experts, and postmyocardial infarction patients were conducted to systematically identify and shortlist appropriate yoga exercises and postures, breathing exercises, meditation and relaxation practices, and lifestyle changes, which were incorporated into a conventional CR framework. The draft intervention was further refined based on the feedback from an internal stakeholder group and an external panel of international experts, before being piloted with yoga instructors and patients with myocardial infarction. A four-phase yoga-based CR (Yoga-CaRe) programme was developed for delivery by a single yoga instructor with basic training. The programme consists of a total of 13 instructor-led sessions (2 individual and 11 group) over a 3-month period. Group sessions include guided practice of yoga exercises and postures, breathing exercises, and meditation and relaxation practices, and support for the lifestyle change and coping through a moderated discussion. Patients are encouraged to self-practice daily at home and continue long-term with the help of a booklet and digital video disc (DVD). Family members/carers are encouraged to join throughout. In conclusion, a novel yoga-based CR programme has been developed, which promises to provide a scalable CR solution for India and an alternative choice for CR globally. It is currently being evaluated in a large multicentre randomised controlled trial across India.

Effectiveness and cost-effectiveness of a Yoga-based Cardiac Rehabilitation (Yoga-CaRe) program following acute myocardial infarction: Study rationale and design of a multi-center randomized controlled trial.

BACKGROUND: Cardiac rehabilitation (CR) is a standard treatment for secondary prevention of acute myocardial infarction (AMI) in high income countries (HICs), but it is inaccessible to most patients in India due to high costs and skills required for multidisciplinary CR teams. We developed a low-cost and scalable CR program based on culturally-acceptable practice of yoga (Yoga-CaRe). In this paper, we report the rationale and design for evaluation of its effectiveness and cost-effectiveness. METHODS: This is a multi-center, single-blind, two-arm parallel-group randomized controlled trial across 22 cardiac care hospitals in India. Four thousand patients aged 18-80 years with AMI will be recruited and randomized 1:1 to receive Yoga-CaRe program (13 sessions supervised by an instructor and encouragement to self-practice daily) or enhanced standard care (3 sessions of health education) delivered over a period of three months. Participants will be followed 3-monthly till the end of the trial. The co-primary outcomes are a) time to occurrence of first cardiovascular event (composite of all-cause mortality, non-fatal myocardial infarction, non-fatal stroke and emergency cardiovascular hospitalization), and b) quality of life (Euro-QoL-5L) at 12 weeks. Secondary outcomes include need for revascularization procedures, return to pre-infarct activities, tobacco cessation, medication adherence, and cost-effectiveness of the intervention. CONCLUSION: This trial will alone contribute >20% participants to existing meta-analyses of randomized trials of CR worldwide. If Yoga-CaRe is found to be effective, it has the potential to save millions of lives and transform care of AMI patients in India and other low and middle income country settings.

Prevalence of heart attack and stroke and associated risk factors among Inuit in Canada: A comparison with the general Canadian population.

BACKGROUND: It is generally believed that cardiovascular disease (CVD) is rare in the Inuit population because of their traditional marine-based diet, but the evidence is inconsistent. OBJECTIVE: To describe the cardiovascular health profile of Canadian Inuit, including disease prevalence, risk factors, country food consumption, and contaminant exposure, and compare to that of the general Canadian population. METHODS: Cardiovascular outcomes and risk factors were obtained for 2070 Inuit adults aged 20-79 years from the Inuit Health Survey (IHS, 2007-2008) and for 3464 general Canadian adults aged 20-79 years from the Canadian Health Measures Survey, Cycle 1 (CHMS, 2007-2009) and Cycle 3 (2012-2013). Sex- and age-specific (20-39, 40-59, 60-79) estimates are reported. To compare results between the IHS and CHMS, age-standardized estimates were calculated for males and females, using the CHMS as the reference population. RESULTS: Inuit had higher prevalence of heart attack (3.1% vs. 1.8% females), stroke (2.1% vs. 0.8% males and 2.2% vs. 1.0% females), diabetes (14.6% vs. 9.0% elderly females), obesity (35.8% vs. 24.2% females), and hypertension (12.2% vs. 2.5% young males and 7.5% vs. 2.5% young females). However, Inuit had better blood lipid profile (hyperlipidemia: 29.0% vs. 46.5% males and 28.4% vs. 35.2% females). Metals and persistent organic pollutant exposures were higher among the Inuit compared with general Canadians. CONCLUSION: Inuit and the general Canadian population differ in cardiovascular health profiles. Further research is needed to characterize the health transition among Inuit, especially among the youth and female.

Enhanced White Matter Integrity in Corpus Callosum of Long-Term Brahmakumaris Rajayoga Meditators.

Meditation has a versatile nature to affect cognitive functioning of human brain. Recent researches demonstrated its effects on white matter (WM) properties of human brain. In this research, we aim to investigate WM microstructure of corpus callosum (CC) in long-term meditators (LTMs) of rajayoga meditation using diffusion tensor imaging. For this cross-sectional analysis, 22 LTMs and 17 control participants of age ranging from 30 to 50 years were recruited. Results show high fractional anisotropy values with low mean diffusivity in whole as well as different segments of CC in the LTM group. Also the experience of meditation was correlated with WM properties of CC tracts. Findings may suggest rajayoga meditation to bring potential changes in microstructure of CC segments. Further studies are suggested in clinical population to check its validity and efficacy against disorders involving agenesis of WM.

Association of blood polychlorinated biphenyls and cholesterol levels among Canadian Inuit.

BACKGROUND: It has generally been thought that Inuit populations have low risk of cardiovascular disease due to high consumption of omega-3 fatty acids found in traditional marine-based diets. However, results of recent surveys showed that Inuit populations are experiencing increasing rates of cardiovascular disease and related risk factors. OBJECTIVE: The purpose of this study was to investigate if blood polychlorinated biphenyls (PCBs) are associated with high cholesterol and related parameters in Canadian Inuit, known risk factors for cardiovascular disease. METHODS: The Adult Inuit Health Survey (IHS, 2007-2008) included 2595 Inuit participants from three regions of the Canadian Arctic, of which 2191 could be classified as with or without high cholesterol. The high cholesterol outcome was defined by LDL-C > 3.36mmol/L or taking medication(s) that reduce cholesterol, and was examined in adjusted logistic regression models with individual blood levels of PCB congeners, sum of dioxin-like PCBs (∑DL-PCBs), or sum of non-dioxin-like PCBs (∑NDL-PCBs). Statistically significant covariates for high cholesterol were ranked in importance according to the proportion of the model log likelihood explained. Continuous clinical parameters of total cholesterol, triglycerides, LDL-C, and HDL-C were examined in multiple linear regression models with ∑DL-PCBs or ∑NDL-PCBs. RESULTS: A total of 719 participants had high cholesterol (32.8%). PCBs were associated with increased risk of high cholesterol, and higher levels of serum triglycerides, total cholesterol, and LDL-C. No association was observed between PCBs and serum HDL-C. With respect to other statistically significant covariates for high cholesterol, the log likelihood ranking of PCBs generally fell between body mass index (BMI) and age. CONCLUSION: Further work is needed to corroborate the associations observed with PCBs and lipids in Canadian Inuit and to examine if they are causal in the direction anticipated.

Cadmium toxicity-induced proline accumulation is coupled to iron depletion.

Investigations were conducted to elucidate the key factor behind Cd2+-toxicity-induced proline accumulation in Indian mustard (Brassica juncea) by raising seedlings, independently in distilled water (DW) and mineral growth medium (MGM) in the presence of 0-500 µM CdCl2. Invariably, Cd2+-induced toxicity, measured in terms of growth, was significantly more prominent in seedlings raised in DW than those raised in MGM. Cd2+ brought about a significant reduction in growth and photosystem II activity with a concomitant increase in proline levels, in a concentration-dependent manner. Interestingly, the level of iron in shoots of seedlings decreased proportionately with increase in Cd2+ toxicity. Cd2+-promoted proline accumulation was significantly higher in seedlings raised in DW than those raised in MGM. Depletion of essential cations (viz. Ca2+, Mg2+, K+, and Fe2+) from MGM one at a time revealed that depletion of Fe2+ leads to maximal proline accumulation under Cd2+ toxicity. Interestingly, proline level in seedlings raised under Cd2+ toxicity in DW supplemented with Fe2+ was similar to that recorded in seedlings raised in MGM. Our results convincingly demonstrated that Cd2+-induced iron deficiency promotes proline accumulation.

Preparation and Preclinical Evaluation of Inhalable Particles Containing Rapamycin and Anti-Tuberculosis Agents for Induction of Autophagy.

PURPOSE: Mycobacterium tuberculosis (Mtb) inhibits host defense mechanisms, including autophagy. We investigated particles containing rapamycin (RAP) alone or in combination with isoniazid (INH) and rifabutin (RFB) for: targeting lung macrophages on inhalation; inducing autophagy; and killing macrophage-resident Mtb and/or augmenting anti-tuberculosis (TB) drugs. METHODS: PLGA and drugs were spray-dried. Pharmacokinetics, partial biodistribution (LC-MS/MS) and efficacy (colony forming units, qPCR, acid fast staining, histopathology) in mice following dry powder inhalation were evaluated. RESULTS: Aerodynamic diameters of formulations were 0.7-4.7 µm. Inhaled particles reached deep lungs and were phagocytosed by alveolar macrophages, yielding AUC0-48 of 102 compared to 0.1 µg/ml × h obtained with equivalent intravenous dose. RAP particles induced more autophagy in Mtb-infected macrophages than solutions. Inhaled particles containing RAP alone in daily, alternate-day and weekly dosing regimens reduced bacterial burden in lungs and spleens, inducing autophagy and phagosome-lysosome fusion. Inhalation of particles containing RAP with INH and RFB cleared the lungs and spleens of culturable bacteria. CONCLUSIONS: Targeting a potent autophagy-inducing agent to airway and lung macrophages alone is feasible, but not sufficient to eliminate Mtb. Combination of macrophage-targeted inhaled RAP with classical anti-TB drugs contributes to restoring tissue architecture and killing Mtb.

The Association Between Health Insurance Coverage and Skilled Birth Attendance in Ghana: A National Study.

OBJECTIVES: Skilled birth attendance (SBA) is a key health intervention used by roughly two-thirds of women in Ghana. The National Health Insurance Scheme provided by the Government of Ghana is widely expected to improve maternal health outcomes by removing financial barriers to health services. In this paper, we examine if indeed health insurance is able to improve SBA, a key maternal outcome. METHODS: We use data from the 2011 Ghana Multiple Indicator Cluster Survey implemented by the Ghana Statistical Services with support from the United Nations Children's Fund (UNICEF). We use a multivariate logistic model controlling for a number of enabling and predisposing factors and past experience with the health system to examine the effect of health insurance on skilled birth attendance. The sample is 2528 women. RESULTS: Our results show that women with health insurance are 47 % more likely to use SBA than women without health insurance. Results also underscore that women with repetitive contact with the health system (such as antenatal care) are more likely to have a skilled delivery (OR 3.00, p value 0.000). We also find that higher parity, rural and poor women are much less likely to use SBA. CONCLUSIONS: Health insurance may indeed be a useful mechanism to improve coverage of SBA, though many barriers to delivery care still exist for women. Further work to understand the effect of health insurance on other maternal outcomes is also warranted.

Anti-breast tumor activity of Eclipta extract in-vitro and in-vivo: novel evidence of endoplasmic reticulum specific localization of Hsp60 during apoptosis.

Major challenges for current therapeutic strategies against breast cancer are associated with drug-induced toxicities. Considering the immense potential of bioactive phytochemicals to deliver non-toxic, efficient anti-cancer therapeutics, we performed bio-guided fractionation of Eclipta alba extract and discovered that particularly the chloroform fraction of Eclipta alba (CFEA) is selectively inducing cytotoxicity to breast cancer cells over non-tumorigenic breast epithelial cells. Our unbiased mechanistic hunt revealed that CFEA specifically activates the intrinsic apoptotic pathway by disrupting the mitochondrial membrane potential, upregulating Hsp60 and downregulating the expression of anti-apoptotic protein XIAP. By utilizing Hsp60 specific siRNA, we identified a novel pro-apoptotic role of Hsp60 and uncovered that following CFEA treatment, upregulated Hsp60 is localized in the endoplasmic reticulum (ER). To our knowledge, this is the first evidence of ER specific localization of Hsp60 during cancer cell apoptosis. Further, our LC-MS approach identified that luteolin is mainly attributed for its anti-cancer activities. Moreover, oral administration of CFEA not only offers potential anti-breast cancer effects in-vivo but also mitigates tumor induced hepato-renal toxicity. Together, our studies offer novel mechanistic insight into the CFEA mediated inhibition of breast cancer and may potentially open up new avenues for further translational research.