Exploring the underlying correlation between microbiota, immune system, hormones, and inflammation with breast cancer and the role of probiotics, prebiotics and postbiotics.

According to recent research, bacterial imbalance in the gut microbiota and breast tissue may be linked to breast cancer. It has been discovered that alterations in the makeup and function of different types of bacteria found in the breast and gut may contribute to growth and advancement of breast cancer in several ways. The main role of gut microbiota is to control the metabolism of steroid hormones, such as estrogen, which are important in raising the risk of breast cancer, especially in women going through menopause. On the other hand, because the microbiota can influence mucosal and systemic immune responses, they are linked to the mutual interactions between cancer cells and their local environment in the breast and the gut. In this regard, the current review thoroughly explains the mode of action of probiotics and microbiota to eradicate the malignancy. Furthermore, immunomodulation by microbiota and probiotics is described with pathways of their activity.

Chemoprotective and immunomodulatory potential of Lactobacillus reuteri against cadmium chloride-induced breast cancer in mice.

INTRODUCTION: The current study aimed to investigate the role of probiotic Lactobacillus reuteri for the treatment and prevention of breast cancer. MATERIALS AND METHODS: Breast cancer was induced by using Cadmium Chloride (Cd) (2 mg/kg) in group II. Tamoxifen was administered to group III. Group IV was treated with Lactobacillus reuteri. Group V was treated with Cd for one month and divided into three subgroups including VA, VB, and VC which were treated with tamoxifen, Lactobacillus reuteri, and tamoxifen + Lactobacillus reuteri, respectively. RESULTS: Significantly higher levels of TNF-α (40.9 ± 4.2 pg/mL), IL-6 (28.0 ± 1.5 pg/mL), IL-10 (60.2 ± 2.0 pg/mL), IFN-γ (60.2 ± 2.0 pg/mL), ALAT (167.2 ± 6.2 U/l), ASAT (451.6 ± 13.9 U/l), and MDA (553.8 ± 19.6 U/l) was observed in Cd group. In comparison, significantly lower levels of TNF-α (18.0 ± 1.1 pg/mL), IL-6 (9.4 ± 0.4 pg/mL), IL-10 (20.8 ± 1.1 pg/mL), IFN-γ (20.8 ± 1.1 pg/mL), ALAT (85.2 ± 3.6 U/l), ASAT (185 ± 6.9 U/l), and MDA (246.0 ± 7.5 U/l) were observed in group Cd + Tam + LR. Liver histopathology of the Cd group showed hemorrhage and ductal aberrations. However, mild inflammation and healthier branched ducts were observed in treatment groups. Furthermore, the renal control group showed normal glomerular tufts, chronic inflammation from the Cd group, and relatively healthier glomerulus with mild inflammation in treatment groups. CONCLUSION: Hence, the preventive and anticancerous role of probiotic Lactobacillus reuteri is endorsed by the findings of the current study.

In search of a 'pan-European value set'; application for EQ-5D-3L.

OBJECTIVES: Country-specific value sets for the EQ-5D are available which reflect preferences for health states elicited from the general population. This allows the transformation of responses on EQ-5D to health state utility values. Only twelve European countries possess country-specific value sets and no value set reflecting the preferences of Europe exists. We aim to estimate a 'pan-European' value set for the EQ-5D-3L, reflecting the preferences for health states of the European population that could help to evaluate health care from the perspective of the European decision-maker. METHODS: We systematically assessed and compared the methodologies of available EQ-5D-3L time trade-off (TTO) value sets from twelve European countries: Denmark, France, Germany, Hungary, Italy, Netherlands, Poland, Portugal, Romania, Slovenia, Spain and UK. Using their published coefficients, a dataset with utility values for all 243 health states was simulated. Different modelling techniques and model specifications including interaction terms were tested. Model selection was based on goodness-of-fit criteria. We also explored results with application of population size weights. RESULTS: Methodological, procedural and analytical characteristics of the included EQ-5D-3L valuation studies were quite comparable. An OLS based model was the preferred model to represent European preferences. Weighting with population size made little difference. CONCLUSIONS: EQ-5D-3L valuation studies were considered of sufficient comparability to form the basis for a new 'pan-European' value set. The method used allows for an easy update when new national value sets become available.

Chemopreventive role of probiotics against cancer: a comprehensive mechanistic review.

Probiotics use different mechanisms such as intestinal barrier improvement, bacterial translocation and maintaining gut microbiota homeostasis to treat cancer. Probiotics' ability to induce apoptosis against tumor cells makes them more effective to treat cancer. Moreover, probiotics stimulate immune function through an immunomodulation mechanism that induces an anti-tumor effect. There are different strains of probiotics, but the most important ones are lactic acid bacteria (LAB) having antagonistic and anti-mutagenic activities. Live and dead probiotics have anti-inflammatory, anti-proliferative, anti-oxidant and anti-metastatic properties which are useful to fight against different diseases, especially cancer. The main focus of this article is to review the anti-cancerous properties of probiotics and their role in the reduction of different types of cancer. However, further investigations are in progress to improve the efficiency of probiotics in cancer treatment.

The association between longer haemodialysis treatment times and hospitalization and mortality after the two-day break in individuals receiving three times a week haemodialysis.

BACKGROUND: On the first haemodialysis (HD) day after the 2-day break in three times a week (3×W) in-centre HD, mortality and hospitalization are higher. If longer HD sessions prescribed 3×W is associated with a reduction in these events is unknown. METHODS: HD session length in 19 557 prevalent European in-centre 3×W HD patients participating in the Dialysis Outcomes and Practice Patterns Study (1998-2011) were categorized into <200, 200-225, 226-250 or >250 min. Standardized event rates on the first (HD1) versus the second (HD2) HD day after the 2-day break, with supporting Cox proportional hazards models adjusted for patient and dialysis characteristics, were generated for all-cause mortality, all-cause hospitalization, out-of-hospital death and fluid overload hospitalization. RESULTS: By comparing HD1 with HD2, increased rates of all endpoints were observed (all P < 0.002). As HD session lengthened across the four groups, all-cause mortality per 100 patient-years on the HD1 (23.0, 20.4, 16.4 and 14.6) and HD2 (26.1, 13.3, 13.4 and 12.1) reduced. Similar improvements were observed for out-of-hospital death but were less marked for hospitalization endpoints. However, even patients dialysing >250 min were at significantly greater risk on HD1 when compared with their HD2 for out-of-hospital death [hazard ratio (HR) = 2.1, 95% CI 1.0-4.3], all-cause hospitalization (HR = 1.3, 95% CI 1.2-1.4) and fluid overload hospitalization (HR = 3.2, 95% CI 1.8-6.0). CONCLUSIONS: Despite the association between reduced mortality across all dialysis days in patients performing longer sessions, elevated risk on the first dialysis day relative to the second persists even in patients dialysing 4.5 h 3×W.

Guideline attainment and morbidity/mortality rates in a large cohort of European haemodialysis patients (EURODOPPS).

BACKGROUND: Haemodialysis patients experience a wide variety of intermediate complications, such as anaemia, hypertension and mineral bone disease (MBD). We aimed to assess the risk of death and hospital admissions as a function of the simultaneous attainment of different guideline targets (for hypertension, anaemia and MBD) in a large European cohort of dialysis patients. METHODS: EURODOPPS is part of the Dialysis Outcomes and Practice Patterns Study (DOPPS) international, prospective cohort study of adult, in-centre haemodialysis patients for whom clinical data are extracted from medical records. In the present analysis, 6317 patients from seven European countries were included between 2009 and 2011. The percentages of patients treated according to the international guidelines on anaemia, hypertension and MBD were determined. The overall degree of guideline attainment was considered to be high if four or all five of the evaluated targets were attained, moderate if two or three targets were attained, and low if fewer than two targets were attained. Fully adjusted multivariate Cox models were used to investigate the relationship of target attainment with mortality and first hospital admission. RESULTS: At baseline, the degree of target attainment was low in 1751 patients (28%), moderate in 3803 (60%) and high in 763 (12%). In the fully adjusted model using time-dependent covariates, low attainment was associated with higher all-cause mortality [hazard ratio (95% confidence interval) = 1.19 (1.05-1.34)] and high attainment was associated with lower all-cause mortality [0.82 (0.68-0.99)]. In a similar model that additionally accounted for death as a competing risk, low and high attainments were not associated with hospital admission. CONCLUSION: In a large international cohort of dialysis patients, we have shown that more stringent application of guidelines is associated with lower mortality.

Attainment of guideline targets in EURODOPPS haemodialysis patients: are differences related to a country's healthcare expenditure and nephrologist workforce?

BACKGROUND: In the field of chronic kidney disease, global clinical practice guidelines have been developed and implemented with a view to improving patient care and outcomes. The attainment of international and European guideline targets for haemodialysis patients in European countries has not been audited recently. Hence, we sought to establish whether the attainment of the targets set out in guidelines and inappropriate care are similar across European countries and whether inter-country differences are related to disparities in national healthcare expenditures (as a percentage of gross domestic product) and/or the nephrologist workforce per capita. METHODS: EURODOPPS is the European part of an international, prospective study of a cohort of adult, in-centre, haemodialysed patients. For the current project, 6317 patients from seven European countries were included between 2009 and 2011. Data on laboratory test results and medication prescriptions were extracted from patient records, in order to determine the overall percentage of patients treated according to the international guidelines on anaemia, dyslipidaemia, metabolic acidosis and mineral bone disease. Data related to macroeconomic indices were collected from World Health Organization database and World Bank stats. RESULTS: Attainment of the targets set in international guidelines was far from complete; only 34.1% of patients attained their target blood pressure and 31.2% attained their target haemoglobin level. Overall, only 5% of the patients attained all of the studied guideline targets. We observed marked inter-country differences in levels of guideline uptake/application and the use of pharmacological agents. The levels of national healthcare expenditures and nephrologist workforce were not correlated with the percentage of patients on-target for ≥50% of the studied variables or with inappropriate care (except for anaemia). CONCLUSIONS: Our analysis of EURODOPPS data highlighted a low overall level of guideline target attainment in Europe and substantial differences between European countries. These inter-country differences did not appear to be linked to macroeconomic determinants.

Subjective memory complaints and the risk of stroke.

BACKGROUND AND PURPOSE: Persons with cognitive impairment, as assessed by cognitive tests, are at a higher risk of stroke. Subjective memory complaints might be an earlier marker for stroke, especially in persons with higher education. Their cognitive reserve might mask their cognitive impairment during cognitive testing. In a population-based setting, we investigated the association between subjective memory complaints and stroke. We simultaneously investigated the association between Mini-Mental State Examination and stroke. We also assessed whether these associations varied with educational level. METHODS: 9152 participants from the Rotterdam Study (baseline 1990-1993 or 2000-2001) completed the subjective memory complaints questionnaire and underwent Mini-Mental State Examination assessment. Subsequently, the entire cohort was followed for incident stroke until 2012. We used Cox proportional hazard models to estimate the associations between subjective memory complaints and Mini-Mental State Examination, with stroke. RESULTS: During a follow-up of 111 593 person years, 1134 strokes were identified, of which 663 were ischemic and 99 hemorrhagic. In the fully adjusted model, presence of subjective memory complaints was independently associated with a higher risk of stroke (hazard ratio, 1.20; 95% confidence interval, 1.04-1.39), but a higher Mini-Mental State Examination was not (hazard ratio per point increase, 0.99; 95% confidence interval, 0.95-1.02). The association between subjective memory complaints and risk of stroke was modified by educational level, with a higher risk of stroke in persons with a higher level of education (hazard ratio, 1.39; 95% confidence interval, 1.07-1.81). CONCLUSIONS: Subjective memory complaints might be an early indicator of stroke risk, especially in highly educated individuals.

Effects of protein intake on blood pressure, insulin sensitivity and blood lipids in children: a systematic review.

High protein intake in early childhood is associated with obesity, suggesting possible adverse effects on other cardiometabolic outcomes. However, studies in adults have suggested beneficial effects of protein intake on blood pressure (BP) and lipid profile. Whether dietary protein intake is associated with cardiovascular and metabolic health in children is unclear. Therefore, we aimed to systematically review the evidence on the associations of protein intake with BP, insulin sensitivity and blood lipids in children. We searched the databases Medline, Embase, Cochrane Central and PubMed for interventional and observational studies in healthy children up to the age of 18 years, in which associations of total, animal and/or vegetable protein intake with one or more of the following outcomes were reported: BP; measures of insulin sensitivity; cholesterol levels; or TAG levels. In the search, we identified 6636 abstracts, of which fifty-six studies met all selection criteria. In general, the quality of the included studies was low. Most studies were cross-sectional, and many did not control for potential confounders. No overall associations were observed between protein intake and insulin sensitivity or blood lipids. A few studies suggested an inverse association between dietary protein intake and BP, but evidence was inconclusive. Only four studies examined the effects of vegetable or animal protein intake, but with inconsistent results. In conclusion, the literature, to date provides insufficient evidence for effects of protein intake on BP, insulin sensitivity or blood lipids in children. Future studies could be improved by adequately adjusting for key confounders such as energy intake and obesity.

Circulating vitamin D, calcium and risk of cerebrovascular disease: a systematic review and meta-analysis.

Available literature suggests that both vitamin D and calcium may be associated with a wide range of non-skeletal outcomes. However, epidemiological evidence supporting their individual associations with incident cerebrovascular disease is scarce. We conducted a systematic review and meta-analysis of prospective cohort studies, published before February 2012 and sought from MEDLINE, EMBASE, BIOSIS and the Science Citation Index databases, and reported cerebrovascular disease (defined as any fatal or non-fatal ischemic stroke, hemorrhagic stroke, cerebrovascular accident or transient ischemic attack) by circulating vitamin D (25-hydroxy vitamin D [25(OH)D] as active metabolite) and calcium levels. Two independent investigators abstracted information on 25(OH)D and calcium, cerebrovascular outcomes and other characteristics from selected studies. Relative risks (RRs) were pooled by both random and fixed effects meta-analyses and were further examined under different study-level characteristics. Publication bias was assessed with funnel plots and Egger's asymmetry test. From 5,778 initial references, nine unique prospective cohort studies met our inclusion criteria. Seven studies (involving 47,809 participants and 926 cerebrovascular events) focused on circulating 25(OH)D and 3 reported on circulating calcium (22,577 participants and 727 events). For 25(OH)D, in a comparison of individuals in the top third versus those in the bottom third at baseline, the combined RR for cerebrovascular disease, adjusted for several conventional risk factors, was 0.60 (95 % CI 0.48, 0.72). The corresponding RR in the prospective studies that reported on baseline circulating calcium levels for cerebrovascular disease was 1.40 (95 % CI 1.19, 1.64). There was no apparent evidence of heterogeneity or publication bias among included studies. Available data indicate that higher circulating level of vitamin D is associated with a decreased risk of cerebrovascular disease. Conversely, higher circulating calcium concentration is associated with an increased risk of cerebrovascular disease.

Conceptual Framework for Optimised Proxy Value Set Selection Through Supra-National Value Set Development for the EQ-5D Instruments.

BACKGROUND: Preference differences between countries and populations justify the use of country-specific value sets for the EQ-5D instruments. There are no clear criteria based on which the selection of value sets for countries without a national value set should be made. As part of the European PECUNIA project, this study aimed to identify factors contributing to differences in preference-based valuations and develop supra-national value sets for homogenous country clusters in Europe. METHODS: A literature review was conducted to identify factors relevant to variations in the EQ-5D-3L/5L health state valuations across countries. Factors fulfilling the pre-specified criteria of validity, reliability, international feasibility and comparability were used to group 27 European Union member states, the European Free Trade Association countries and the UK. Clusters of countries were developed based on the frequency of their appearance in the same grouping. The supra-national value sets were estimated for these clusters from the coefficients of existing published valuation studies using the ordinary least-squares model. RESULTS: Ten factors were identified from 69 studies. From these, five grouping variables: (1) culture and religion; (2) linguistics; (3) healthcare system typology; (4) healthcare system financing; and (5) sociodemographic aspects were derived to define the groups of homogenous countries. Frequency-based grouping revealed five cohesive clusters: English-speaking, Nordic, Central-Western, Southern and Eastern European. CONCLUSIONS: European countries were clustered considering variables that may relate to differences in health state valuations. Supra-national value sets provide optimised proxy value set selection in the lack of a national value set and/or for regional decision making.

A Value Set for the EQ-5D-Y-3L in the Netherlands.

BACKGROUND AND OBJECTIVE: There is increasing interest in preference-accompanied measures of health for paediatric populations. The child-friendly EQ-5D version, EQ-5D-Y-3L, is one such instrument, but the lack of a Dutch value set prevents its use in economic evaluations of healthcare interventions in the Netherlands. This study aims at covering this gap by collecting preferences using a standardised protocol for deriving EQ-5D-Y-3L value sets. METHODS: Composite time trade-off data were collected using videoconferencing interviews, with each respondent completing ten composite time trade-off tasks. Discrete choice experiment data were collected using an online survey, with respondents each completing 15 paired comparisons. Respondents completed these tasks considering what they prefer for a hypothetical 10-year-old child. Discrete choice experiment data were analysed using a ten-parameter mixed-logit model and anchored to the quality-adjusted life-year scale using the mean observed composite time trade-off values. RESULTS: The study collected preferences for 197 respondents using composite time trade-off and for 959 respondents using a discrete choice experiment. The discrete choice experiment sample was representative for the Dutch population in terms of age and sex. The level 3 weight for pain/discomfort was the largest, followed by feeling worried, sad or unhappy, usual activities, mobility and self-care. Health state values ranged between -0.218 and 1. CONCLUSIONS: This study generated a Dutch value set for the EQ-5D-Y-3L, which can be used for the computation of quality-adjusted life-years for economic evaluations of healthcare interventions in paediatric populations.

In a Child's Shoes: Composite Time Trade-Off Valuations for EQ-5D-Y-3L with Different Proxy Perspectives.

BACKGROUND AND OBJECTIVES: EQ-5D-Y-3L health states are commonly valued by asking adults to complete stated preference tasks, 'given their views about a 10-year-old child' (hereafter referred to as proxy 1). The use of this perspective has been a source of debate. In this paper, we investigated an alternative proxy perspective: i.e. adults considered what they think a 10-year old-child would decide for itself (hereafter, proxy 2 (substitute)]. Our main objective was to explore how the outcomes, dispersion and response patterns of a composite time trade-off valuation differ between proxy 1 and proxy 2. METHODS: A team of four trained interviewers completed 402 composite time trade-off interviews following the EQ-5D-Y-3L protocol. Respondents were randomly allocated to value health states in either the proxy 1 or proxy 2 (substitute) perspective. Each respondent valued ten health states with the perspective they were assigned to, as well as one health state with the alternative perspective (33333). RESULTS: The use of different proxy perspectives yielded differences in EQ-5D-Y-3L valuation. For states in which children had considerable pain and were very worried, sad or unhappy, respondents' valuations were lower in proxy 1 than in proxy 2 (substitute) perspectives, by about 0.2. Within-subject variation across health states was lower for proxy 2 (substitute) than proxy 1 perspectives. Analyses of response patterns suggest that data for proxy 2 (substitute) perspectives were less clustered. CONCLUSIONS: There are systematic differences between composite time trade-off responses given by adults deciding for children and adults considering what children would want for themselves. In addition to warranting further qualitative exploration, such differences contribute to the ongoing normative discussion surrounding the source and perspective used for valuation of child and adolescent health.

Productivity of Working at Home and Time Allocation Between Paid Work, Unpaid Work and Leisure Activities During a Pandemic.

BACKGROUND AND OBJECTIVE: The COVID-19 pandemic and the measures taken by governments to contain it have affected many aspects of the daily lives of citizens. This study aimed to describe changes in the productivity of paid work and time allocation to paid and unpaid work and leisure resulting from working at home during the pandemic. METHODS: A sample of 851 people from the Netherlands who had paid work (≥ 24 h/week) and worked at least 4 hours per week extra at home because of lockdown measures completed a questionnaire during the first COVID-19 lockdown (April 2020). Respondents reported time spent on paid and unpaid work and leisure before and during the lockdown. Productivity was measured in terms of quantity and quality of paid work. RESULTS: On average, respondents spent less time (14%) on paid work and productivity decreased 5.5%. Changes in productivity were associated with the age of children, net income and having a separate home office. Respondents spent more time on unpaid work (27%) and leisure (11%). Women spent more time on unpaid work in absolute but not in relative terms. People with a partner and with children spent more time on unpaid work and less time on leisure. CONCLUSIONS: Productivity of paid work decreased, and people reallocated time between paid and unpaid work and leisure during the first COVID-19 lockdown. Changes in time allocation and productivity differed across subgroups. If working at home becomes more common, future research should focus on the long-term impact on productivity and mental and physical health.

Prevalence and Risk of Mild Cognitive Impairment in Low and Middle-Income Countries: A Systematic Review.

BACKGROUND: Mild cognitive impairment (MCI) is a cognitive state associated with increased risk of dementia. Little research on MCI exists from low-and middle-income countries (LMICs), despite high prevalence of dementia in these settings. OBJECTIVE: This systematic review aimed to review epidemiological reports to determine the prevalence of MCI and its associated risk factors in LMICs. METHODS: Medline, Embase, and PsycINFO were searched from inception until November 2019. Eligible articles reported on MCI in population or community-based studies from LMICs and were included as long as MCI was clearly defined. RESULTS: 5,568 articles were screened, and 78 retained. In total, n = 23 different LMICs were represented; mostly from China (n = 55 studies). Few studies were from countries defined as lower-middle income (n = 14), low income (n = 4), or from population representative samples (n = 4). There was large heterogeneity in how MCI was diagnosed; with Petersen criteria the most commonly applied (n = 26). Prevalence of amnesic MCI (aMCI) (Petersen criteria) ranged from 0.6%to 22.3%. Similar variability existed across studies using the International Working Group Criteria for aMCI (range 4.5%to 18.3%) and all-MCI (range 6.1%to 30.4%). Risk of MCI was associated with demographic (e.g., age), health (e.g., cardio-metabolic disease), and lifestyle (e.g., social isolation, smoking, diet and physical activity) factors. CONCLUSION: Outside of China, few MCI studies have been conducted in LMIC settings. There is an urgent need for population representative epidemiological studies to determine MCI prevalence in LMICs. MCI diagnostic methodology also needs to be standardized. This will allow for cross-study comparison and future resource planning.

Effect modification of FADS2 polymorphisms on the association between breastfeeding and intelligence: results from a collaborative meta-analysis.

BACKGROUND: Accumulating evidence suggests that breastfeeding benefits children's intelligence, possibly due to long-chain polyunsaturated fatty acids (LC-PUFAs) present in breast milk. Under a nutritional adequacy hypothesis, an interaction between breastfeeding and genetic variants associated with endogenous LC-PUFAs synthesis might be expected. However, the literature on this topic is controversial. METHODS: We investigated this gene × environment interaction through a collaborative effort. The primary analysis involved >12 000 individuals and used ever breastfeeding, FADS2 polymorphisms rs174575 and rs1535 coded assuming a recessive effect of the G allele, and intelligence quotient (IQ) in Z scores. RESULTS: There was no strong evidence of interaction, with pooled covariate-adjusted interaction coefficients (i.e. difference between genetic groups of the difference in IQ Z scores comparing ever with never breastfed individuals) of 0.12[(95% confidence interval (CI): -0.19; 0.43] and 0.06 (95% CI: -0.16; 0.27) for the rs174575 and rs1535 variants, respectively. Secondary analyses corroborated these results. In studies with ≥5.85 and <5.85 months of breastfeeding duration, pooled estimates for the rs174575 variant were 0.50 (95% CI: -0.06; 1.06) and 0.14 (95% CI: -0.10; 0.38), respectively, and 0.27 (95% CI: -0.28; 0.82) and -0.01 (95% CI: -0.19; 0.16) for the rs1535 variant. CONCLUSIONS: Our findings did not support an interaction between ever breastfeeding and FADS2 polymorphisms. However, subgroup analysis suggested that breastfeeding may supply LC-PUFAs requirements for cognitive development if breastfeeding lasts for some (currently unknown) time. Future studies in large individual-level datasets would allow properly powered subgroup analyses and further improve our understanding on the breastfeeding × FADS2 interaction.

Association of alcohol consumption with allergic disease and asthma: a multi-centre Mendelian randomization analysis.

AIMS: To use the rs1229984 variant associated with alcohol consumption as an instrument for alcohol consumption to test the causality of the association of alcohol consumption with hay fever, asthma, allergic sensitization and serum total immunoglobulin (Ig)E. DESIGN: Observational and Mendelian randomization analyses using genetic variants as unbiased markers of exposure to estimate causal effects, subject to certain assumptions. SETTING: Europe. PARTICIPANTS: We included a total of 466 434 people aged 15-82 years from 17 population-based studies conducted from 1997 to 2015. MEASUREMENTS: The rs1229984 (ADH1B) was genotyped; alcohol consumption, hay fever and asthma were self-reported. Specific and total IgE were measured from serum samples. FINDINGS: Observational analyses showed that ever-drinking versus non-drinking, but not amount of alcohol intake, was positively associated with hay fever and inversely associated with asthma but not with allergic sensitization or serum total immunoglobulin (Ig)E. However, Mendelian randomization analyses did not suggest that the observational associations are causal. The causal odds ratio (OR) per genetically assessed unit of alcohol/week was an OR = 0.907 [95% confidence interval (CI) = 0.806, 1.019; P = 0.101] for hay fever, an OR = 0.897 (95% CI = 0.790, 1.019; P = 0.095) for asthma, an OR = 0.971 (95% CI =  0.804, 1.174; P = 0.763) for allergic sensitization and a 4.7% change (95% CI = -5.5%, 14.9%; P = 0.366) for total IgE. CONCLUSIONS: In observational analyses, ever-drinking versus not drinking was positively associated with hay fever and negatively associated with asthma. However, the Mendelian randomization results were not consistent with these associations being causal.

Perspective About Mental Illnesses: A Survey Of Health Care Providers Of Abbottabad.

BACKGROUND: Mental Health problems are widespread globally and are the leading causes of disability. The lives of people living with mental illnesses are often drastically altered by the symptoms of the illness and made worse by the society's reaction. Stigmatizing attitude among general population is prevalent. Relatively less research has been done to explore the attitude of health care providers towards mental illness especially so in Pakistan. This study aims to investigate views of healthcare providers of Abbottabad regarding mental illnesses. METHODS: A cross-sectional study was conducted in major hospitals and medical institutes of Abbottabad wherein 640 selfadministered questionnaires based on Opening Minds Scale for Healthcare Providers (OMS-HC) were distributed among healthcare providers selected through non-probability convenience sampling; 553 (86.41%) were returned. Data was collected from June to September 2016 and analyzed using SPSS-16.0. RESULTS: The mean age of the participants is 26.12 years±7.612. Majority 346 (62%) were medical students, 60 (10.8%) were teachers, 50 (9%) were house officers, 70 (12.7%) were trainee medical officers, 27 (4.9%) were consultants. There were 313 (56.6%) females. The highest degree of stigma was observed among the 'Attitudes' of the people while it was relatively lower in Disclosure and Help Seeking domain and least in the factor of Social Distance. CONCLUSIONS: Stigma associated with mental illness is prevalent among healthcare providers..

Association of Blood Pressure and Arterial Stiffness With Cognition in 2 Population-Based Child and Adult Cohorts.

Background High blood pressure levels and higher arterial stiffness have been shown to be associated with lower cognition during adulthood, possibly by accumulative changes over time. However, vascular factors may already affect the brain during early life. Methods and Results We examined the relation between cognition and vascular factors within 5853 children from the Generation R Study (mean age 6.2 years) and 5187 adults from the Rotterdam Study (mean age 61.8 years). Diastolic and systolic blood pressure and arterial stiffness were assessed, the latter by measuring pulse-wave velocity and pulse pressure. For cognition, the Generation R Study relied on nonverbal intelligence, whereas the Rotterdam Study relied on a cognitive test battery to calculate the g-factor, a measure of global cognition. In the Generation R Study, standardized diastolic blood pressure showed a significant association with standardized nonverbal intelligence (ß=-0.030, 95% confidence interval=[-0.054; -0.005]) after full adjustment. This association held up after excluding the top diastolic blood pressure decile (ß=-0.042 [-0.075; -0.009]), suggesting that the relation holds in normotensives. Within the Rotterdam Study, standardized cognition associated linearly with standardized systolic blood pressure (ß=-0.036 [-0.060; -0.012]), standardized pulse-wave velocity (ß=-0.064 [-0.095; -0.033]), and standardized pulse pressure (ß=-0.044 [-0.069; -0.020], and nonlinearly with standardized diastolic blood pressure (quadratic term ß=-0.032 [-0.049; -0.015]) after full adjustment. Conclusions Blood pressure and cognition may already be related in the general population during early childhood, albeit differently than during adulthood.