SWI/SNF complex prevents lineage reversion and induces temporal patterning in neural stem cells.

Members of the SWI/SNF chromatin-remodeling complex are among the most frequently mutated genes in human cancer, but how they suppress tumorigenesis is currently unclear. Here, we use Drosophila neuroblasts to demonstrate that the SWI/SNF component Osa (ARID1) prevents tumorigenesis by ensuring correct lineage progression in stem cell lineages. We show that Osa induces a transcriptional program in the transit-amplifying population that initiates temporal patterning, limits self-renewal, and prevents dedifferentiation. We identify the Prdm protein Hamlet as a key component of this program. Hamlet is directly induced by Osa and regulates the progression of progenitors through distinct transcriptional states to limit the number of transit-amplifying divisions. Our data provide a mechanistic explanation for the widespread tumor suppressor activity of SWI/SNF. Because the Hamlet homologs Evi1 and Prdm16 are frequently mutated in cancer, this mechanism could well be conserved in human stem cell lineages. PAPERCLIP:

Joint associations of diet and physical activity with incident type 2 diabetes and hypertension: an analysis of 144,288 UK Biobank participants.

BACKGROUND: Studies examining the joint associations of lifestyle exposures can reveal novel synergistic and joint effects, but no study has examined the joint association of diet and physical activity (PA) with type 2 diabetes (T2D) and hypertension. The aim of this study is to examine the joint associations of PA and diet with incidence of type T2D and hypertension, as a combined outcome and separately in a large sample of UK adults. METHODS: This prospective cohort study included 144,288 UK Biobank participants aged 40-69. Moderate to vigorous PA (MVPA) was measured using the International Physical Activity Questionnaire and a wrist accelerometer. We categorised PA and diet indicators (diet quality score (DQS) and energy intake (EI)) based on tertiles and derived joint PA and diet variables. Outcome was major cardiometabolic disease incidence (combination of T2D and hypertension). RESULTS: A total of 14,003(7.1%) participants developed T2D, 28,075(19.2%) developed hypertension, and 30,529(21.2%) developed T2D or hypertension over a mean follow-up of 10.9(3.7) years. Participants with middle and high self-reported MVPA levels had lower risk of major cardiometabolic disease regardless of diet, e.g. among high DQS group, hazard ratios in middle and high MVPA group were 0.90 (95%CI:0.86-0.94), and 0.88(95%CI:0.84-0.92), respectively. Participants with jointly high device-measured MVPA and high DQS levels had lower major cardiometabolic disease risk (HR: 0.84, 95%CI:0.71-0.99). The equivalent joint device-measured MVPA and EI exposure analyses showed no clear pattern of associations with the outcomes. CONCLUSION: Higher PA is an important component in cardiometabolic disease prevention across all diet quality and total EI groups. The observed lack of association between diet health outcomes may stem from a lower DQS.

Body shape phenotypes of multiple anthropometric traits and cancer risk: a multi-national cohort study.

BACKGROUND: Classical anthropometric traits may fail to fully represent the relationship of weight, adiposity, and height with cancer risk. We investigated the associations of body shape phenotypes with the risk of overall and site-specific cancers. METHODS: We derived four distinct body shape phenotypes from principal component (PC) analysis on height, weight, body mass index (BMI), waist (WC) and hip circumferences (HC), and waist-to-hip ratio (WHR). The study included 340,152 men and women from 9 European countries, aged mostly 35-65 years at recruitment (1990-2000) in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: After a median follow-up of 15.3 years, 47,110 incident cancer cases were recorded. PC1 (overall adiposity) was positively associated with the risk of overall cancer, with a HR per 1 standard deviation (SD) increment equal to 1.07 (95% confidence interval 1.05 to 1.08). Positive associations were observed with 10 cancer types, with HRs (per 1 SD) ranging from 1.36 (1.30-1.42) for endometrial cancer to 1.08 (1.03-1.13) for rectal cancer. PC2 (tall stature with low WHR) was positively associated with the risk of overall cancer (1.03; 1.02-1.04) and five cancer types which were not associated with PC1. PC3 (tall stature with high WHR) was positively associated with the risk of overall cancer (1.04; 1.03-1.05) and 12 cancer types. PC4 (high BMI and weight with low WC and HC) was not associated with overall risk of cancer (1.00; 0.99-1.01). CONCLUSIONS: In this multi-national study, distinct body shape phenotypes were positively associated with the incidence of 17 different cancers and overall cancer.

Body mass index and cancer risk among adults with and without cardiometabolic diseases: evidence from the EPIC and UK Biobank prospective cohort studies.

BACKGROUND: Whether cancer risk associated with a higher body mass index (BMI), a surrogate measure of adiposity, differs among adults with and without cardiovascular diseases (CVD) and/or type 2 diabetes (T2D) is unclear. The primary aim of this study was to evaluate separate and joint associations of BMI and CVD/T2D with the risk of cancer. METHODS: This is an individual participant data meta-analysis of two prospective cohort studies, the UK Biobank (UKB) and the European Prospective Investigation into Cancer and nutrition (EPIC), with a total of 577,343 adults, free of cancer, T2D, and CVD at recruitment. We used Cox proportional hazard regressions to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between BMI and incidence of obesity-related cancer and in turn overall cancer with a multiplicative interaction between BMI and the two cardiometabolic diseases (CMD). HRs and 95% CIs for separate and joint associations for categories of overweight/obesity and CMD status were estimated, and additive interaction was quantified through relative excess risk due to interaction (RERI). RESULTS: In the meta-analysis of both cohorts, BMI (per ~ 5 kg/m2) was positively associated with the risk of obesity-related cancer among participants without a CMD (HR: 1.11, 95%CI: 1.07,1.16), among participants with T2D (HR: 1.11, 95% CI: 1.05,1.18), among participants with CVD (HR: 1.17, 95% CI: 1.11,1.24), and suggestively positive among those with both T2D and CVD (HR: 1.09, 95% CI: 0.94,1.25). An additive interaction between obesity (BMI ≥ 30 kg/m2) and CVD with the risk of overall cancer translated into a meta-analytical RERI of 0.28 (95% CI: 0.09-0.47). CONCLUSIONS: Irrespective of CMD status, higher BMI increased the risk of obesity-related cancer among European adults. The additive interaction between obesity and CVD suggests that obesity prevention would translate into a greater cancer risk reduction among population groups with CVD than among the general population.

Associations of changes in physical activity and diet with incident obesity and changes in adiposity: Longitudinal findings from the UK Biobank.

We examined the association of changes in physical activity and diet with obesity development and changes in body fat percentage, body mass index, and waist circumference. 31,344 adults without obesity at baseline (age = 56.0 ± 7.5 years; female = 49.1%) from the UK Biobank were included. Physical activity was categorised based on public health guidelines as: inactive; insufficient; and sufficient. Diet category was assigned based on an established composited score that included consumption of fruits, vegetables, fish, red meat (unprocessed), and processed meat. Diet was categorised as: poor; reasonable; and good. Physical activity and diet changes were categorised based on changes in category: worsened; stable; increased (physical activity)/improved (diet). During a mean follow up of 6.8 (SD = ±2.3) years, 1354 (4.3%) participants developed obesity. Compared to stable physical activity-diet, increasing physical activity was associated with the lowest obesity odds, across diet changes (e.g., OR [95%CI]: diet worsened (0.89 [0.69, 1.15]); diet improved (0.65 [0.48, 0.89])). Increasing physical activity with improved diet was associated with the largest difference in body fat percentage (ß:-0.62 [-0.82, -0.41]), body mass index (-0.37 [-0.47, -0.28]), and waist circumference (-1.21 [-1.63, -0.79]). Excluding adults with a history of smoking, or major illness, lowered obesity odds among participants with increased physical activity by an additional 11%-21%. In those who decreased physical activity obesity was attenuated when combined with diet improvement. Improvements in physical activity or diet mutually attenuated the deleterious associations of the other behaviour's deterioration. In most analyses, increases in physical activity conferred consistent positive associations against the development of obesity, across dietary change groups.

Joint association of alcohol consumption and adiposity with alcohol- and obesity-related cancer in a population sample of 399,575 UK adults.

Obesity and alcohol consumption are both important modifiable risk factors for cancer. We examined the joint association of adiposity and alcohol consumption with alcohol- and obesity-related cancer incidence. This prospective cohort study included cancer-free UK Biobank participants aged 40-69 years. Alcohol consumption was categorised based on current UK guidelines into four groups. We defined three markers of adiposity: body fat percentage (BF %), waist circumference and BMI and categorised each into three groups. We derived a joint alcohol consumption and adiposity marker variable with twelve mutually exclusive categories. Among 399 575 participants, 17 617 developed alcohol-related cancer and 20 214 developed obesity-related cancer over an average follow-up of 11·8 (SD 0·9) years. We found relatively weak evidence of independent associations of alcohol consumption with cancer outcomes. However, the joint association analyses showed that across all adiposity markers, above guideline drinkers who were in the top two adiposity groups had elevated cancer incidence risk (e.g. HR for alcohol-related cancer was 1·53 (95 % CI (1·24, 1·90)) for within guideline drinkers and 1·61 (95 % CI (1·30, 2·00)) for above guideline drinkers among participants who were in the top tertile BF %. Regardless of alcohol consumption status, the risk of obesity-related cancer increased with higher adiposity in a dose-response manner within alcohol consumption categories. Our study provides guidance for public health priorities aimed at lowering population cancer risk via two key modifiable risk factors.

Association between vegetarian diet and gouty arthritis: A retrospective cohort study.

BACKGROUND AND AIMS: A vegetarian diet is rich in vegetables, fruits, and soy products. Although vegetarian diet is beneficial for improving the health outcomes such as body mass index, metabolic syndrome, cardiovascular disease, and mortality rate, the association between a vegetarian diet and gout incidence is not well known. METHODS AND RESULTS: We linked the MJ Health Survey Data and MJ Biodata 2000 with the National Health Insurance Research Database (NHIRD) and the National Registration of Death (2000-2018). Information on the diet was collected from the MJ Health Survey Data, and the incidence of gouty arthritis was confirmed using the NHIRD. The Kaplan-Meier survival curve and log-rank test were used to compare the differences between vegetarian and non-vegetarian participants. Cox regression models were used to estimate the risk of the incidence of gouty arthritis. Among 76,972 participants, 37,297 (48.46%) were men, 2488 (3.23%) were vegetarians and the mean age was 41.65 ± 14.13 years. The mean baseline uric acid level was 6.14 ± 1.65 mg/dL. A total of 16,897 participants developed gouty arthritis, including 16,447 (22.08%) non-vegetarians and 450 (18.9%) vegetarians over a mean follow-up of 19 years. Significant differences were observed in the Kaplan-Meier survival curves between vegetarians and non-vegetarians (log-rank p < 0.001). Vegetarians had a significantly decreased incidence of gouty arthritis compared with non-vegetarians (hazard ratio = 0.87, 95% confidence interval = 0.78-0.98, p = 0.02) after adjusting for potential confounders. CONCLUSION: People with a vegetarian diet had a significantly decreased risk of developing gouty arthritis compared with non-vegetarians in Taiwan.

Dynamics of activating and repressive histone modifications in Drosophila neural stem cell lineages and brain tumors.

During central nervous system development, spatiotemporal gene expression programs mediate specific lineage decisions to generate neuronal and glial cell types from neural stem cells (NSCs). However, little is known about the epigenetic landscape underlying these highly complex developmental events. Here, we perform ChIP-seq on distinct subtypes of Drosophila FACS-purified NSCs and their differentiated progeny to dissect the epigenetic changes accompanying the major lineage decisions in vivo By analyzing active and repressive histone modifications, we show that stem cell identity genes are silenced during differentiation by loss of their activating marks and not via repressive histone modifications. Our analysis also uncovers a new set of genes specifically required for altering lineage patterns in type II neuroblasts (NBs), one of the two main Drosophila NSC identities. Finally, we demonstrate that this subtype specification in NBs, unlike NSC differentiation, requires Polycomb-group-mediated repression.

Associations of changes in physical activity and discretionary screen time with incident obesity and adiposity changes: longitudinal findings from the UK Biobank.

BACKGROUND: Physical activity (PA) and discretionary screen time (DST; television and computer use during leisure) are both associated with obesity risk, but little longitudinal evidence exists on their combined influence. This study examined the independent and joint associations of changes in PA and DST with incident obesity, body mass index (BMI) and waist circumference (WC). METHODS: We analysed the data of individuals aged 40-69 years from the UK Biobank, a large-scale, population-based prospective cohort study. PA was measured using the International Physical Activity Questionnaire and DST was defined as the total of daily TV viewing and non-occupational computer use. Changes in PA and DST over time were defined using departure from sex-specific baseline tertiles and categorised as worsened (PA decreased/DST increased), maintained, and improved (PA increased/DST decreased). We then used each exposure change to define a joint PA-DST change variable with nine mutually exclusive groups. We used multivariable adjusted mixed-effects linear and Poisson models to examine the independent and joint associations between PA and DST changes with BMI and WC and incident obesity, respectively. Development of a BMI ≥ 30 kg/m2 was defined as incident obesity. RESULTS: Among 30,735 participants, 1,628 (5.3%) developed incident obesity over a mean follow-up of 6.9 (2.2) years. In the independent association analyses, improving PA (Incident Rate Ratio (IRR) 0.46 (0.38-0.56)) was associated with a lower risk of incident obesity than maintaining PA, maintaining DST, or improving DST. Compared to the referent group (both PA and DST worsened), all other combinations of PA and DST changes were associated with lower incident obesity risk in the joint association analyses. We observed substantial beneficial associations in the improved PA groups, regardless of DST change [e.g., DST worsened (IRR 0.31 (0.21-0.44)), maintained (IRR 0.34 (0.25-0.46)), or improved (IRR 0.35 (0.22-0.56)]. The most pronounced decline in BMI and WC was observed when PA was maintained or improved and DST was maintained. CONCLUSION: We found that improved PA had the most pronounced beneficial associations with incident obesity, irrespective of DST changes. Improvements in PA or DST mutually attenuated the deleterious effects of the other behaviour's deterioration.

Changes in physical activity and adiposity with all-cause, cardiovascular disease, and cancer mortality.

BACKGROUND: The relationship between joint changes in physical activity and adiposity with mortality is not well understood. We examined the association of changes in these two established risk factors with all-cause (ACM), cardiovascular disease (CVD), and cancer mortality. METHODS: We used longitudinal data from Taiwan's MJ Cohort, comprising 116,228 general population adults recruited from 1998-2013 with repeated measures 4.6 y (2.5) apart and followed up for mortality for 11.9 y (3.5). Physical activity, body mass index (BMI), waist circumference (WC), and body fat percentage (BF%) groups and changes were based on public health and clinical guidelines. RESULTS: Compared to stable-insufficient physical activity, increasing physical activity from any baseline level was associated with lower ACM (HR [95%CI]): 0.85 [0.74, 0.96]) and CVD mortality (0.72 [0.55, 0.93]) risk. This was approximately equal to meeting physical activity guidelines at both timepoints (eg: 0.71 [0.58, 0.88] for CVD mortality). Compared to stable-overweight/moderate adiposity, decreasing adiposity level attenuated but did not offset mortality risk for all three outcomes (eg: BMI = 0.95 [0.76, 1.16] for CVD mortality). Only maintaining a healthy adiposity level at both timepoints offset mortality risk (BMI = 0.75 [0.61, 0.89]) for CVD mortality). In the joint changes analyses, lower mortality risk was a consequence of increases in physical activity across adiposity change groups (eg: WC decrease = 0.57 [0.48, 0.67]; WC stability = 0.73 [0.66, 0.80], WC increase = 0.83 [0.72, 0.97] for ACM). Decreasing adiposity attenuated the negative associations of decreased physical activity (BF% = 1.13 [0.95, 1.35] for ACM). CONCLUSIONS: We found a lower risk for ACM, CVD, and cancer mortality from increasing physical activity and an attenuation from decreasing adiposity regardless of baseline levels. The beneficial associations of joint changes were primarily driven by physical activity, suggesting lower mortality risk may be more immediate through physical activity improvements compared to adiposity improvements alone.

A randomized clinical trial to investigate the effect of dietary protein sources on periodontal health.

AIM: The aim was to assess two macronutrient interventions in a 2 × 2 factorial dietary design to determine their effects on oral health. MATERIALS AND METHODS: Participants (65-75 years old) with a body mass index between 20 and 35 kg/m2 of a larger randomized control trial who consented to an oral health assessment were recruited. They had ad libitum access to one of four experimental diets (omnivorous higher fat or higher carbohydrate, semi-vegetarian higher fat or higher carbohydrate) for 4 weeks. The periodontal examination included periodontal probing depth (PPD), clinical attachment level (CAL), and bleeding on probing. Oral plaque and gingival crevicular fluid (GCF) were collected before and after the intervention. RESULTS: Between baseline and follow up, the number of sites with a CAL <5 mm (mean difference [MD] -5.11 ± 9.68, p = .039) increased and the GCF amount (MD -23.42 ± 39.42 Periotron Units [PU], p = .050) decreased for the semi-vegetarian high-fat diet. For the mean proportion of sites with PPD reduction of >1 mm and CAL gain of >1 mm, significant differences were calculated between the diets investigated. The clinical parameters were not associated with changes in the oral microbiota. CONCLUSIONS: The results of this study provided evidence that a semi-vegetarian high-fat diet provides benefits to clinical parameters of periodontal health. This study is registered in ClinicalTrials.gov (ACTRN12616001606471).

Diet Quality following Total Meal Replacement Compared with Food-Based Weight-Loss Diets in Postmenopausal Women with Obesity: A Secondary Analysis of the TEMPO Diet Trial.

BACKGROUND: Severely energy-restricted diets that utilize meal-replacement products are the most effective dietary treatment for obesity. However, there are concerns they may fail to educate individuals on how to adopt a healthy food-based diet after weight loss. OBJECTIVES: The aim of this research was to compare changes in diet quality following total meal replacement compared with food-based weight-loss diets. METHODS: In this secondary analysis of a randomized controlled trial, 79 postmenopausal women aged 45-65 y, with a BMI (in kg/m2) of 30-40, were randomly assigned to either a total meal-replacement diet (energy intake restricted by 65-75% relative to requirements) for 16 wks, followed by a food-based diet (energy intake restricted by 25-35% relative to requirements) until 52 wks, or the food-based diet for the entire 52-wk period. Diet quality was scored at baseline and 52 wks using the Healthy Eating Index for Australian Adults, with score changes compared between groups using an independent t test. RESULTS: Diet quality improved from baseline in both groups, but less so in the total meal-replacement group, with a mean (SD) increase of 3.6 (10.8) points compared with 11.8 (13.9) points in the food-based group, resulting in a mean between-group difference of -8.2 (P = 0.004; 95% CI: -13.8, -2.7) points. This improvement in diet quality within both groups was mostly driven by a reduction in the intake of discretionary foods. Intake remained below the recommendations at 52 wks for 4 of the 5 food groups in both dietary interventions. CONCLUSIONS: In postmenopausal women with obesity, weight-loss interventions that involve either a total meal-replacement diet or a food-based diet both improve diet quality, however, not sufficiently to meet recommendations. This highlights the importance of addressing diet quality as a part of all dietary weight-loss interventions. This trial is registered with the Australia and New Zealand Clinical Trials Registry as 12612000651886.

Lifestyle risk factors and infectious disease mortality, including COVID-19, among middle aged and older adults: Evidence from a community-based cohort study in the United Kingdom.

In this community-based cohort study, we investigated the relationship between combinations of modifiable lifestyle risk factors and infectious disease mortality. Participants were 468,569 men and women (56.5 ± 8.1, 54.6% women) residing in the United Kingdom. Lifestyle indexes included traditional and emerging lifestyle risk factors based on health guidelines and best practice recommendations for: physical activity, sedentary behaviour, sleep quality, diet quality, alcohol consumption, and smoking status. The main outcome was mortality from infectious diseases, including pneumonia, and coronavirus disease 2019 (COVID-19). Meeting public health guidelines or best practice recommendations among combinations of lifestyle risk factors was inversely associated with mortality. Hazard ratios ranged between 0.26 (0.23-0.30) to 0.69 (0.60-0.79) for infectious disease and pneumonia. Among participants with pre-existing cardiovascular disease or cancer, hazard ratios ranged between 0.30 (0.25-0.34) to 0.73 (0.60-0.89). COVID-19 mortality risk ranged between 0.42 (0.28-0.63) to 0.75 (0.49-1.13). We found a beneficial dose-response association with a higher lifestyle index against mortality that was consistent across sex, age, BMI, and socioeconomic status. There was limited evidence of synergistic interactions between most lifestyle behaviour pairs, suggesting that the dose-response relationship among different lifestyle behaviours is not greater than the sum of the risk induced by each behaviour. Improvements in lifestyle risk factors and meeting public health guidelines or best practice recommendations could be used as an ancillary measure to ameliorate infectious disease mortality.

Alcohol drinking in one's thirties and forties is associated with body mass index in men, but not in women: A longitudinal analysis of the 1970 British Cohort Study.

Our objective was to investigate longitudinal associations between alcohol drinking and body mass index (BMI). Alcohol drinking (exposure), BMI (outcome), smoking habit, occupation, longstanding illness, and leisure time physical activity (potential confounders) were assessed at ages 30, 34, 42, and 46 in the 1970 British Birth Cohort Study. Multilevel models were used to cope with the problem of correlated observations. There were 15,708 observations in 5931 men and 14,077 observations in 5656 women. Drinking was associated with BMI in men. According to the regression coefficients, BMI was expected to increase by 0.36 (95% confidence interval: 0.11, 0.60) kg/m2 per year in men who drank once a week and by 0.40 (0.14, 0.15) kg/m2 per year in men who drank most days. In ten years, BMI was expected to increase by 5.4 kg/m2 in men who drank and by 2.9 kg/m2 in men who drank and were physically active. Drinking was not associated with BMI in women. Rather, BMI was expected to increase by 0.25 (0.07, 0.43) kg/m2 per year in women who were former smokers. In ten years, BMI was expected to increase by 4.3 kg/m2 in women who were former smokers and by 0.8 kg/m2 in women who were former smokers and who were physically active. Associations between drinking and BMI were similar after further adjustment for problematic drinking and diet. These longitudinal data suggest that drinking is associated with BMI in men and that drinking is not associated with BMI in women independent of other lifestyle risk factors.

Formation of advanced glycation endproducts in foods during cooking process and underlying mechanisms: a comprehensive review of experimental studies.

Advanced glycation endproducts (AGE) are a group of complex and heterogeneous molecules, sharing some common characteristics such as covalent cross-link formation among proteins, the effect of transforming the colour of food products into yellow-brown colours and fluorescence formation. AGE are linked to many diseases including diabetes, renal diseases, CVD, liver diseases, neuro-degenerative and eye disorders, female reproductive dysfunction, and even cancer. AGE are formed endogenously but are also provided from exogenous sources including diet and tobacco. Western diet, rich in processed and/or heat-treated foods, fat and sugar, increases the exposure to AGE. The foods that contain high levels of fat and protein are generally rich in terms of AGE, and are also prone to AGE formation during cooking compared with carbohydrate-rich foods such as vegetables, fruits, legumes and whole grains. The present article aimed to review the literature about the effects of different cooking methods and conditions on the AGE content of food and AGE formation mechanisms using a comprehensive approach.

Impact of three different plate colours on short-term satiety and energy intake: a randomized controlled trial.

BACKGROUND: Plate colour was previously shown to alter the amount of food consumption due to its environmental effect on food intake. However, different studies have indicated that the effect of plate colour cannot be generalized. In light of this finding, the main objective of this study was to determine whether food consumption during an open buffet meal was different when using same-sized white, red or black plates. METHODS: This study was a crossover study conducted with 54 female participants aged 18-30 years with normal BMIs. On experimental days, participants ate a standard breakfast and were then randomly assigned to eat ad libitum lunch (pasta with tomato sauce and soft drinks) using white, red or black plates. Visual analogue scale (VAS) scores on satiety outcomes were measured for all meals. Energy and macronutrient intake during lunch was recorded. RESULTS: The results showed that plate colour exerted a significant effect on food intake during the test days (p = 0.021). The average total energy intake with red (1102.16 ± 47.12 kcal, p = 0.05) and black plates (1113.19 ± 47.12 kcal, p = 0.034) was significantly increased when compared to that with white plates (945.72 ± 47.12 kcal). There were no differences between red and black plates (p = 0.985). Overall, mean VAS scores did not indicate a significant difference between the groups. CONCLUSIONS: Plate colour may be a crucial determinant of energy intake.

Is aluminum exposure a risk factor for neurological disorders?

Aluminum (Al) is widely found in the nature. Although the relation between Al and neurodegenerative diseases is still controversial, Al is related with many brain diseases including Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Al exposure occurs mainly through environment, occupational, and dietary factors for humans. Al exposure with diet can be through foods, food additives, water, and contamination of Al equipment/utensils. The aim of this review is to summarize various hypotheses, which link Al and neurodegeneration, and to determine the roles of Al exposure through different sources including diet, environment, and occupation. Future studies should be done in vulnerable subgroups of population including children, patients receiving antacid or Al-containing pharmeteucials on a daily basis, patients with reduced renal function, and patients on parenteral nutrition regimens that are likely to be affected by possible adverse health effects of Al. In addition, gender, age, and Al interactions need to be determined. One of the most important challanges in future epidemiological studies is to determine which variables should be controlled. In addition, experimental studies should be more focused and translational. In this context, exposure dose, dose-response effects, and time lapse between exposures and cognitive assessments are very important.

Doppler Tissue Evaluation of Atrial Conduction Properties in Patients With Non-alcoholic Fatty-liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in clinical practice, and there is an increasing trend in its prevalence in the general population. Recent studies have demonstrated increased risk of atrial fibrillation (AF) in NAFLD. However, information on the mechanism of increased risk of AF in NAFLD is lacking. Impaired atrial conduction is an important factor in the pathophysiology of AF. We aimed to investigate atrial conduction properties in patients with NAFLD by tissue Doppler echocardiography. Fifty-nine ultrasound diagnosed NAFLD patients without clinical diagnosis of hypertension, diabetes mellitus, or cardiac disease and 22 normal subjects as controls were included in this study. Atrial conduction properties were assessed by electromechanical delay (EMD) derived from Doppler tissue echocardiography examination and P-wave dispersion (PWD) calculated from the 12-lead electrocardiogram. Inter-atrial and intra-atrial EMD intervals were significantly longer in NAFLD patients than in controls (inter-atrial EMD, 31.9 ± 8.5 ms vs. 23.4 ± 4.6 ms,p= 0.0001, and intra-atrial EMD, 14.3 ± 5.2 vs. 10.2 ± 4.0 ms,p= 0.001). Similarly, PWD was significantly higher in NAFLD patients compared with controls (49.2 ± 6.3 ms vs. 43.3 ± 4.2 ms,p= 0.0001). Maximum left atrial volume was also significantly higher in the NAFLD group than in controls (51 ± 11 mL vs. 34 ± 9 mL,p< 0.0001). This study demonstrated that atrial conduction is impaired in patients with NAFLD. Also, in a patient population of NAFLD without any clinical diagnosis of cardiac disease, diabetes, or hypertension, left atrial volume was increased compared with controls. These findings suggest impaired atrial conduction as a factor in increased risk of AF in NAFLD.

Development of acute pulmonary hypertension after bortezomib treatment in a patient with multiple myeloma: a case report and the review of the literature.

Bortezomib is widely used in treatment of multiple myeloma. In recent years, severe bortezomib-induced lung injury has been reported. The clinical course is generally characterized with fever and dyspnea, followed by respiratory failure with pulmonary infiltrates. Herein, we report a 57-year-old man with newly diagnosed multiple myeloma admitted with dyspnea, fever, and hypotension on the third day of the first dose of bortezomib therapy. He had bilateral jugular venous distention, crackles at the bases of the lungs and hepatomegaly. Transthoracic echocardiography revealed acute pulmonary hypertension (PH) with an estimated pressure of 70 mm Hg. The perfusion scintigraphy ruled out pulmonary embolism, and microbiological examination was negative. On his course, fever, dyspnea, hypoxia, and pulmonary vascular pressure subsided rapidly. The sudden onset of PH and its rapid decrement without any treatment suggests bortezomib as the underlying cause. Subsequently, the patient did not respond to vincristine-doxorubicin-dexamethasone regimen and thalidomide. Bortezomib treatment was repeated, and no pulmonary adverse reactions occurred. Follow-up echocardiographies revealed pulmonary arterial pressures to be maximally of 35 mm Hg. To our knowledge, this is the first case of acute PH after front-line bortezomib therapy. In this report, we review bortezomib-related pulmonary complications in the literature and possible underlying mechanisms.

Two-dimensional strain and strain rate imaging of the left atrium and left ventricle in adult patients with atrial septal defects before and after the later stage of percutaneous device closure.

AIM: Atrial septal defect (ASD) causes chronic volume overload of the right heart. The potential adverse effects of this long-standing volume overload to left atrium (LA) and left ventricle (LV) and their response to ASD closure has been poorly studied. METHODS: We studied 20 ASD patients before the procedure, at the 24-hour and 1 month following the percutaneous closure. Twenty age-matched controls served as the control group. The analysis for atrial deformation was performed on the lateral wall, mid segment of the LA from apical four-chamber view. Peak longitudinal strain (S) and strain rate (SR) during LA reservoir, passive emptying, atrial contraction phases and LV global longitudinal systolic S and SR were measured. RESULTS: Peak S and SR at LA reservoir, conduit and late contraction phases in ASD patients were similar to controls. All of these parameters increased immediately after the closure of the defect. Similarly, SLV and SRLV in ASD patients were not significantly different from the controls and significantly increased after the closure. But LA S, SR and LV S, SR results decreased in 1 month after the closure. SLV in ASD patients was significantly correlated with echocardiographic findings and the invasively measured defect size. CONCLUSION: LA and LV S and SR are not significantly affected in ASD patients. However, correction of the long-standing volume overload by percutaneous closure causes an early increase in LA and LV longitudinal deformation that correlates with the magnitude of the atrial septal defect. But this increase decreased in 1 month after closure.