Leisure-time and occupational physical activity and risk of cardiovascular disease incidence: a systematic-review and dose-response meta-analysis of prospective cohort studies.

BACKGROUND AND OBJECTIVE: Physical activity has benefits for the cardiovascular system, however, what levels and types of activity provide optimal cardiovascular health is unclear. We aimed to determine the level of physical activity that has the most benefits against cardiovascular diseases (CVD). METHODS: PubMed, Scopus, and Web of Science were searched for prospective cohort studies on leisure-time (LTPA) or occupational physical activity (OPA) as the exposure and major types of CVD (total CVD, coronary heart disease [CHD], stroke, and atrial fibrillation [AF]) incidence as the outcome. Risk of bias of studies was evaluated using the ROBINS-I tool. Summary hazard ratios (HR) were calculated using random-effects pairwise model. RESULTS: A total of 103 studies were included in the analysis. The highest versus the lowest LTPA was associated with a lower risk of overall CVD (HR = 0.81; 95% CI: 0.77-0.86), CHD (HR = 0.83; 0.79-0.88), and stroke (HR = 0.83; 0.79-0.88), but not AF (HR = 0.98; 0.92-1.05). Linear dose-response analyses showed a 10%, 12%, 9%, and 8% risk reduction in CVD, CHD, stroke, and AF incidence, respectively, for every 20 MET-hours/week increase in LTPA. In nonlinear dose-response analyses, there were inverse associations up to 20 MET-hours/week with 19% and 20% reduction in CVD and CHD risk, and up to 25 MET-hours/week with 22% reduction in stroke, with no further risk reduction at higher LTPA levels. For AF, there was a U-shaped nonlinear association with the maximum 8% risk reduction at 10 MET-hours/week of LTPA. Higher levels of OPA were not associated with risk of CVD, CHD, stroke, or AF. CONCLUSIONS: Overall, results showed an inverse dose-response relationship between LTPA and risk of CVD, CHD, stroke, and AF. Running was the most beneficial LTPA but the risk was similar among various LTPA intensities. OPA showed no benefits in total or any type of CVD.

The relationship between major food sources of fructose and cardiovascular disease, cancer, and all-cause mortality: a systematic review and dose-response meta-analysis of cohort studies.

We aimed to summarize the associations between food sources of fructose and cardiovascular diseases (CVD), cancer, and all-cause mortality risk using a systematic review and meta-analysis. We searched PubMed, Scopus, and Web of Science up to November 2020. We included cohort studies that investigated the relationship between mortality risk (all-cause, CVD, specific CVD, and total and site-specific cancers) and intake of ≥1 food source of fructose (fruit, fruit juice, breakfast cereals, sugar-sweetened beverages (SSBs), sweets, and yogurt) in general adult population. Summary hazard ratios and 95% CIs were estimated using a random-effects model for linear and nonlinear relationships. Findings indicated that each 100 g/d increase in fruit intake was associated with 8-13% lower risk of CVDs, stroke, gastrointestinal, and lung cancer mortality. For all-cause mortality, there was a beneficial relationship up to 200 g/d fruit, and then plateaued. For ischemic heart disease and cancer mortality, there was a beneficial relationship up to 300 g/d followed by a slight increase. Ingestion of breakfast cereals and sweets was also associated with lower risk of all-cause mortality. For yogurt, a non-linear marginal decrease in all-cause mortality was found. Ingestion of each 200 g/d yogurt was associated with a 14% lower risk of CVD mortality. Every 60 g/d increase in sweet intake was linked to a 5% lower risk of all-cause mortality. Contrariwise, every 250 g/d increase in SSBs intake was associated with 7-10% higher risk of all-cause and CVD mortality. In conclusion, beneficial associations were found between fruit, breakfast cereals, sweets, and yogurt with all-cause and/or CVD mortality risk. Fruit intake had also an inverse link with cancer mortality. Conversely, SSBs had a harmful relationship with all-cause and CVD mortality.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.2000361 .Registry number: CRD42019144956.

Maternal circulating leptin, tumor necrosis factor-alpha, and interleukine-6 in association with gestational diabetes mellitus: a systematic review and meta-analysis.

Background: Over the last decade, an emerging role of novel cytokines in the pathogenesis of gestational diabetes mellitus (GDM) has been proposed. The present study was implemented to provide a more accurate estimate of the effect size of the association between leptin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) and the risk of GDM.Methods: Online databases were looked up to January 2023 using the search string: (leptin OR TNF-α OR IL-6) AND "gestational diabetes." Observational studies investigating the association of selected cytokines and GDM risk were included. Odds ratios and their 95% confidence intervals (CIs) were extracted and random-effects models were used to estimate the pooled effect.Results: Twenty-four studies were included in the meta-analysis. A significant association was found between higher circulating leptin and the risk of GDM and the pooled estimate was 1.16 (95%CI: 1.07, 1.27). Higher circulating levels of IL-6 and TNF-α were associated with increased risk of GDM, and the pooled estimates were 1.35 (95%CI: 1.05, 1.73) and 1.28 (95%CI: 1.01, 1.62), respectively.Conclusions: The studied cytokines could be implicated in the GDM pathogenesis and used as potential biomarkers for assessing the GDM risk. Additional longitudinal studies with large sample sizes are needed for a further evaluation of these findings.

Comparing the risk of cardiovascular diseases and all-cause mortality in four lifestyles with a combination of high/low physical activity and healthy/unhealthy diet: a prospective cohort study.

BACKGROUND: In this study, we assessed the risk of cardiovascular diseases (CVDs) and all-cause mortality in subjects having an only physical activity or a healthy diet or both compared to those having none of these healthy behaviors in the Golestan Cohort Study (GCS). METHODS: A total of 50,045 participants aged ≥ 40 years were recruited from Golestan Province, Iran, from 2004 to 2008 and followed for a median of 13.9 years. Four lifestyles were compared: healthy diet and active (HDA), healthy diet but inactive (HDI), unhealthy diet but active (UDA), and unhealthy diet and inactive (UDI), with UDI being considered as the reference group. Diet quality was assessed by the Dietary Approaches to Stop Hypertension diet score, which was calculated based on a validated food frequency questionnaire. The primary outcomes were death from any cause and CVDs. Adjusted Cox models were used to estimate the hazards ratio (HR) and 95% confidence intervals (CI) for overall and CVDs mortality. RESULTS: During 467,401 person-years of follow-up, 6,256 overall deaths and 2,043 confirmed CVDs deaths were reported. After adjustment for potential confounders, there was a significant lower risk for all-cause mortality in participants with both healthy behaviors (HR = 0.79, 95% CI = 0.73 to 0.86) or only one healthy behavior [HDI: HR = 0.84, 95% CI = 0.78 to 0.90)] and [UDI: HR = 0.91, 95% CI = 0.85 to 0.97] compared to those with both unhealthy behaviors. For CVDs mortality, the HDA lifestyle (HR = 0.74, 95%CI = 0.65 to 0.86), as well as the UDA lifestyle (HR = 0.83, 95%CI = 0.74 to 0.94) indicated a significant lower risk compared to the UDI lifestyle. The HDI lifestyle was not more effective than UDI. CONCLUSION: The greatest reduction in all-cause and CVDs mortality was related to the HDA. For all-cause mortality, both HDI and UDA lifestyles were associated with a decreased risk in comparison to UDI, but for CVDs mortality, only UDA but not HDI decreased the risk.

The effect of vitamin D supplementation on oxidative stress and inflammatory biomarkers in pregnant women: a systematic review and meta-analysis of clinical trials.

BACKGROUND: Vitamin D deficiency, a common problem among pregnant women, is linked with maternal inflammation, oxidative stress and consequent adverse pregnancy outcomes. The aim of this systematic review was to evaluate the effect of vitamin D supplementation on oxidative stress and inflammatory biomarkers in pregnant women according to the PRISMA guidance. METHODS: Four databases including PubMed/MEDLINE, Scopus, Web of Science and Cochrane were used for searching papers published until 25th July 2022. Clinical trials that assessed 25-Hydroxyvitamin D (25(OH)D), inflammatory markers (including high sensitivity C-reactive protein (hs-CRP) and certain cytokines) and oxidative stress markers (including malondialdehyde (MDA), total antioxidant capacity (TAC) and glutathione (GSH)) in pregnant women, were included in this review. The primary search of three databases displayed 21571 records. After removing duplicates and irrelevant articles, 17 eligible RCTs included for more evaluation. Random effect model and Der Simonian-Laird method were used to pool the data of studies. Risk of bias assessed according to version 2 of the Cochrane risk-of-bias tool for randomized trials. RESULTS: According to the meta-analysis result, vitamin D supplementation caused a significant increase in the maternal circulating concentrations of 25(OH)D (SMD 2.07; 95%, CI 1.51, 2.63; p < 0.001), TAC (SMD 2.13, 95% CI 1.04 to 3.23, p < 0.001) and GSH (SMD 4.37, 95% CI 2.9 to 5.74, p < 0.001) as well as a significant decrease in the levels of MDA (SMD -0.46, 95% CI -0.87 to -0.05, p = 0.02). However, it had no significant impact on hs-CRP concentrations (SMD 0.24; 95% CI, -0.55, 1.03; p = 0.50). CONCLUSION: In the present study, vitamin D supplementation led to increased levels of 25(OH)D, TAC and GSH and also decreased concentration of MDA. Nevertheless, because of low certainty of evidence, these findings have to be declared conservatively. TRIAL REGISTRATION: Registration code in PROSPERO website: CRD42020202600.

Endothelial damage and dysfunction in acute graft-versus-host disease.

Clinical studies suggested that endothelial dysfunction and damage could be involved in the development and severity of acute graft-versus-host disease (aGVHD). Accordingly, we found increased percentage of apoptotic Casp3+ blood vessels in duodenal and colonic mucosa biopsies of patients with severe aGVHD. In murine experimental aGVHD, we detected severe microstructural endothelial damage and reduced endothelial pericyte coverage accompanied by reduced expression of endothelial tight junction proteins leading to increased endothelial leakage in aGVHD target organs. During intestinal aGVHD, colonic vasculature structurally changed, reflected by increased vessel branching and vessel diameter. Because recent data demonstrated an association of endothelium-related factors and steroid refractory aGVHD (SR-aGVHD), we analyzed human biopsies and murine tissues from SR-aGVHD. We found extensive tissue damage but low levels of alloreactive T cell infiltration in target organs, providing the rationale for T-cell independent SR-aGVHD treatment strategies. Consequently, we tested the endothelium-protective PDE5 inhibitor sildenafil, which reduced apoptosis and improved metabolic activity of endothelial cells in vitro. Accordingly, sildenafil treatment improved survival and reduced target organ damage during experimental SR-aGVHD. Our results demonstrate extensive damage, structural changes, and dysfunction of the vasculature during aGVHD. Therapeutic intervention by endothelium-protecting agents is an attractive approach for SR-aGVHD complementing current anti-inflammatory treatment options.

The effect of fasting and energy restricting diets on markers of glucose and insulin controls: a systematic review and meta-analysis of randomized controlled trials.

Inconsistencies exist with regard to influence of fasting and energy-restricting diets on markers of glucose and insulin controls. To address these controversial, this study was conducted to determine the impact of fasting diets on fasting blood sugars (FBSs), insulin, homeostatic model assessment insulin resistance (HOMA-IR) and hemoglobin A1c (HbA1c) levels. A comprehensive systematic search was carried out in electronic databases, i.e., Scopus, PubMed, and Web of Science through June 2019 for RCTs that investigated the impact of fasting and energy-restricting diets on circulating FBS, insulin, HOMA-IR and HbA1c levels from. Weighted mean difference (WMD) with the 95% CI were used for estimating combined effect size. The subgroup analysis was applied to specify the source of heterogeneity among articles. Pooled results from 30 eligible articles with 35 arms demonstrated a significant decrease in FBS (WMD): -3.376 mg/dl, 95% CI: -5.159, -1.594, p < 0.001), insulin (WMD: -1.288 µU/ml, 95% CI: -2.385, -0.191, p = 0.021), HOMA-IR (WMD: -0.41 mg/dl, 95% CI: -0.71, -0.10, p = 0.01) levels following fasting or energy-restricting diets. Nevertheless, no significant changes were observed in serum HbA1c levels. The subgroup analyses showed that overweight or obese people with energy restricting diets and treatment duration >8 weeks had a greater reduction in FBS, insulin and HOMA-IR level compared with other subgroups. The evidence from available studies suggests that the fasting or energy-restricting diets leads to significant reductions in FBS, insulin and HOMA-IR level and has modest, but, non-significant effects on HbA1c levels.

GAA gene mutation detection following clinical evaluation and enzyme activity analysis in Azeri Turkish patients with Pompe disease.

Pompe disease (PD) is a rare autosomal recessive multi-systemic lysosomal storage disorder, caused by mutations in the acid alpha-glucosidase (GAA) gene located on 17q25.2-q25.3. It is one of about 50 rare genetic diseases categorized as lysosomal storage disorders. This disease is characterized by a range of different symptoms related to acid alpha-glucosidase deficiency. Mutation recognition in the GAA gene can be very significant for purposes such as therapeutic interference, early diagnosis and genotype-phenotype relationship. In the current study, peripheral blood samples were gathered from patients with PD and healthy members of three families. Enzymatic activity of GAA was checked. Then, mutation detection was performed by polymerase chain reaction followed by direct sequencing of all exons in samples with decreased enzyme activity. The identified mutations were investigated using bioinformatics tools to predict possible effects on the protein product and also to compare the mutated sequence with near species. Three novel mutations (c.1966-1968delGAG, c.2011-2012delAT and c.1475-1481dupACCCCAC) were identified in the GAA gene. Assessment of the effects of these mutations on protein structure and function showed the possibility of harmful effects and their significant alterations in the protein structure. The three novel GAA gene mutations detected in this study expand the information about the molecular genetics of PD and can be used to helpdiagnosis and genetic counseling of affected families.

Neutrophil activation by Candida glabrata but not Candida albicans promotes fungal uptake by monocytes.

Candida albicans and Candida glabrata account for the majority of candidiasis cases worldwide. Although both species are in the same genus, they differ in key virulence attributes. Within this work, live cell imaging was used to examine the dynamics of neutrophil activation after confrontation with either C. albicans or C. glabrata. Analyses revealed higher phagocytosis rates of C. albicans than C. glabrata that resulted in stronger PMN (polymorphonuclear cells) activation by C. albicans. Furthermore, we observed differences in the secretion of chemokines, indicating chemotactic differences in PMN signalling towards recruitment of further immune cells upon confrontation with Candida spp. Supernatants from co-incubations of neutrophils with C. glabrata primarily attracted monocytes and increased the phagocytosis of C. glabrata by monocytes. In contrast, PMN activation by C. albicans resulted in recruitment of more neutrophils. Two complex infection models confirmed distinct targeting of immune cell populations by the two Candida spp.: In a human whole blood infection model, C. glabrata was more effectively taken up by monocytes than C. albicans and histopathological analyses of murine model infections confirmed primarily monocytic infiltrates in C. glabrata kidney infection in contrast to PMN-dominated infiltrates in C. albicans infection. Taken together, our data demonstrate that the human opportunistic fungi C. albicans and C. glabrata are differentially recognized by neutrophils and one outcome of this differential recognition is the preferential uptake of C. glabrata by monocytes.

Image-based systems biology of infection.

The successful treatment of infectious diseases requires interdisciplinary studies of all aspects of infection processes. The overarching combination of experimental research and theoretical analysis in a systems biology approach can unravel mechanisms of complex interactions between pathogens and the human immune system. Taking into account spatial information is especially important in the context of infection, since the migratory behavior and spatial interactions of cells are often decisive for the outcome of the immune response. Spatial information is provided by image and video data that are acquired in microscopy experiments and that are at the heart of an image-based systems biology approach. This review demonstrates how image-based systems biology improves our understanding of infection processes. We discuss the three main steps of this approach--imaging, quantitative characterization, and modeling--and consider the application of these steps in the context of studying infection processes. After summarizing the most relevant microscopy and image analysis approaches, we discuss ways to quantify infection processes, and address a number of modeling techniques that exploit image-derived data to simulate host-pathogen interactions in silico.

Quantitative image analysis of cell colocalization in murine bone marrow.

Long-term antibody production is a key property of humoral immunity and is accomplished by long-lived plasma cells. They mainly reside in the bone marrow, whose importance as an organ hosting immunological memory is becoming increasingly evident. Signals provided by stromal cells and eosinophils may play an important role for plasma cell maintenance, constituting a survival microenvironment. In this joint study of experiment and theory, we investigated the spatial colocalization of plasma cells, eosinophils and B cells by applying an image-based systems biology approach. To this end, we generated confocal fluorescence microscopy images of histological sections from murine bone marrow that were subsequently analyzed in an automated fashion. This quantitative analysis was combined with computer simulations of the experimental system for hypothesis testing. In particular, we tested the observed spatial colocalization of cells in the bone marrow against the hypothesis that cells are found within available areas at positions that were drawn from a uniform random number distribution. We find that B cells and plasma cells highly colocalize with stromal cells, to an extent larger than in the simulated random situation. While B cells are preferentially in contact with each other, i.e., form clusters among themselves, plasma cells seem to be solitary or organized in aggregates, i.e., loosely defined groups of cells that are not necessarily in direct contact. Our data suggest that the plasma cell bone marrow survival niche facilitates colocalization of plasma cells with stromal cells and eosinophils, respectively, promoting plasma cell longevity.

The Effect of Family-Centered Intervention on Key Indicators of Diabetes Management and Control in Patients with Type-2 Diabetes.

Background: This study is to determine the effect of the family-centered intervention (FCIS) on the key indicators of diabetes management and Control control in patients with type-2 diabetes. Method: The present study is a quiz- experimental study with a randomized control group. Participants were 64 patients with type-2 diabetes visiting Ali Asghar Hospital of Isfahan in 2018. The eligible patients were assigned to either the intervention group or the control group (i.e., patient-center care) through block randomization. FCIS were implemented in 4 two-hour sessions as home visits while the patients and their caregivers were present. Data were collected twice-i.e. before the intervention and 12 weeks after it- and were analyzed, by running a t-test (α = 0.05), using SPSS-21. Results: The mean ± SD age of participants was 50.4 ± 8.5. There was no significant difference between the two groups in the mean weight, serum levels of FBS and A1C, physical activity, energy intake, and BMI before intervention. But, a significant improvement in the mean values of these variables in the intervention group after the intervention, compared with the control group was indicated (P < 0.05). Conclusions: This study suggests that FCIS are more effective than patient-center care in the management and control of type-2 diabetes. Therefore, it is recommended that the family be considered in educational interventions.

Covariates of a healthy diet and physical activity self-management one year after Bariatric surgery: A cross-sectional study.

BACKGROUND: Healthy diet and physical activity self-management is important in maintaining weight loss and preventing weight regain after bariatric surgery. We aimed at evaluating covariates of healthy diet and physical activity self-management among patients undergone bariatric surgery using Health Action Process Approach (HAPA) model. METHOD: In this cross-sectional study, 272 patients with a history of bariatric surgery were selected from the data registry of Tehran Obesity Treatment Study (TOTS). Data were collected using bariatric surgery self-management standard questionnaire (BSSQ), and items based on HAPA model for healthy diet and physical activity self-management. Data were analyzed using Path analysis and AMOS version 24. RESULTS: The mean score of self-management was (32 ± 10SD). Coping planning construct (ß = 0.22; p<0.001) and risk perception (ß = 0.02; p<0.01) in dietary self-management and action planning (ß = 0.16; p = 0.001) and risk perception (ß = 0.001; p = 0.17) in physical activity self-management had the highest and lowest effect powers, respectively. Coping planning (ß = 0.22; p<0.001) and action planning (ß = 0.17; p<0.03) in diet, and action planning (ß = 0.16; p = 0.010) in physical activity were significantly related to self-management. Also, task-coping self-efficacy (ß = 0.28; and p<0.001), outcome expectancies (ß = 0.37; p<0.001), risk perception (ß = 0.13; p = 0.015) in diet and coping self-efficacy (ß = 0.50; p<0.001), outcome expectancies (ß = 0.12; p = 0.021) in physical activity were significantly related to behavioral intention. The values of CFI = 0.939 and RMSEA = 0.052 for diet and CFI = 0.948 and RMSEA = 0.048 for physical activity indicated adequate fit. CONCLUSION: HAPA was applicable as a framework for interventions promoting healthy diet and physical activity self-management in patients who have undergone bariatric surgery.

The effects of fasting diets on nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. There is no confirmed treatment for NAFLD as yet. Recently, fasting regimens and their relationship to NAFLD have drawn a great deal of attention in the literature. We review the current evidence that supports fasting diets as an adjunctive therapeutic strategy for patients with NAFLD and address potential action mechanisms. We reason that the fasting diets might be a promising approach for modulating hepatic steatosis, fibroblast growth factors 19 and 21 signaling, lipophagy, and the metabolic profile.

Enhancement of cisplatin-induced apoptosis by saffron in human lung cancer cells.

BACKGROUND: Cisplatin is a prevalent chemotherapeutic agent, and it has been used extensively to treat lung cancer. However, its clinical efficacy is hampered by its safety profile and dose-limiting toxicity. Saffron is a natural product that has shown significant anticancer effects. The combination treatment of saffron with chemotherapeutic agents has been considered a new strategy. METHODS: Herein, saffron extract as a natural anticancer substance was combined with cisplatin to assess their combined efficacy against tumor development in vitro. In A549 and QU-DB cell lines, the combined effect of the saffron extract with cisplatin led to a significant reduction in cell viability as compared to cisplatin alone. RESULTS: After 48 h incubation a considerable reduction in ROS levels in the QU-DB cell line upon treatment with cisplatin in the presence of saffron extract in comparison with cells treated with cisplatin alone. Furthermore, apoptosis increased significantly when in cells treated with cisplatin in combination with saffron extract compared to cisplatin alone. CONCLUSION: Our data establish that the combination of saffron extract as a natural anticancer substance with cisplatin leads to improved cell toxicity of cisplatin as an anticancer agent. Therefore, the saffron extract could be potentially used as an additive to enable a reduction in cisplatin dosages and its side effects.

Fasting diets: what are the impacts on eating behaviors, sleep, mood, and well-being?

Fasting diets (FDs) have drawn great attention concerning their contribution to health and disease over the last decade. Despite considerable interest in FDs, the effect of fasting diets on eating behaviors, sleep, and mood-essential components of diet satisfaction and mental health- has not been addressed comprehensively. Understanding the critical role that fasting plays in these elements will open up potential treatment avenues that have not yet been explored. The aim of the present paper was to conduct a comprehensive critical review exploring the effects of fasting on eating behaviors, sleep, and mood. There is currently a lack of clarity regarding which fasting option yields the most advantageous effects, and there is also a scarcity of consistent trials that assess the effects of FDs in a comparable manner. Similarly, the effects and/or treatment options for utilizing FDs to modify eating and sleep behaviors and enhance mood are still poorly understood. Further researches aiming at understanding the impacts of various fasting regimes, providing new insights into the gut-brain axis and offering new treatment avenues for those with resistant anxiety and depression, are warranted. Alteration of eating behaviors can have lasting effects on various physiological parameters. The use of fasting cures can underpin ancient knowledge with scientific evidence to form a new approach to the prevention and treatment of problems associated with co-morbidities or challenges pertaining to eating behaviors. Therefore, a thorough examination of the various fasting regimens and how they impact disease patterns is also warranted.

Dietary Advanced Glycation End Products and Risk of Overall and Cause-Specific Mortality: Results from the Golestan Cohort Study.

Controversy exists regarding the association of dietary advanced glycation end products (dAGEs) with the risk of disease outcomes and mortality. We aimed to examine, prospectively, the association between dAGEs intake and the risk of overall and cause-specific mortality in the Golestan Cohort Study. The cohort was conducted between 2004 and 2008 in Golestan Province (Iran) recruiting 50,045 participants aged 40-75 years. Assessment of dietary intake over the last year was performed at baseline using a 116-item food frequency questionnaire. The dAGEs values for each individual were calculated based on published databases of AGE values of various food items. The main outcome was overall mortality at the time of follow-up (13.5 years). Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and cause-specific mortality were estimated according to the dAGEs quintiles. During 656, 532 person-years of follow-up, 5406 deaths in men and 4722 deaths in women were reported. Participants at the highest quintile of dAGE had a lower risk of overall mortality (HR: 0.89, 95% CI: 0.84, 0.95), CVD mortality (HR: 0.89, 95% CI: 0.84, 0.95), and death from other causes (HR: 0.89, 95% CI: 0.84, 0.95) compared to those in the first quintile after adjusting for confounders. We found no association of dAGEs with risk of mortality from cancer (all), respiratory and infectious diseases, and injuries. Our findings do not confirm a positive association between dAGEs and the risk of mortality in Iranian adults. There is still no agreement among studies investigating dAGEs and their health-related aspects. So, further high-quality studies are required to clarify this association.

Linoleic acid potentiates CD8+ T cell metabolic fitness and antitumor immunity.

The metabolic state represents a major hurdle for an effective adoptive T cell therapy (ACT). Indeed, specific lipids can harm CD8+ T cell (CTL) mitochondrial integrity, leading to defective antitumor responses. However, the extent to which lipids can affect the CTL functions and fate remains unexplored. Here, we show that linoleic acid (LA) is a major positive regulator of CTL activity by improving metabolic fitness, preventing exhaustion, and stimulating a memory-like phenotype with superior effector functions. We report that LA treatment enhances the formation of ER-mitochondria contacts (MERC), which in turn promotes calcium (Ca2+) signaling, mitochondrial energetics, and CTL effector functions. As a direct consequence, the antitumor potency of LA-instructed CD8 T cells is superior in vitro and in vivo. We thus propose LA treatment as an ACT potentiator in tumor therapy.

The Effect of Vitamin D Supplementation on Serum 25-Hydroxy Vitamin D in the Patients Undergoing Bariatric Surgery: a Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Currently, there is no consensus on the optimal vitamin D administration in bariatric patients. The present systematic review and meta-analysis were conducted to examine the effect of vitamin D supplements on serum level of 25(OH) vitamin D in the patients undergoing bariatric surgery (BS).Random model effects were used to estimate standardized mean difference (SMD) with a 95% confidence interval (CI). Nine clinical trials were included in the meta-analysis. Vitamin D supplementation in patients undergoing BS modestly improves vitamin D status (SMD, 0.53; 95% CI, 0.28, 0.77) particularly, in the dosages above 2850 IU/day and in the patients with BMI greater than 50 kg/m2. Vitamin D supplementation was associated with prevention of raising of the PTH serum concentration and without impact on serum calcium levels.

Severity of Disease and COVID-19 Complications During Hospital Stay: A Prospective Cohort Study.

BACKGROUND: COVID-19, with its high transmission and mortality rates and unknown outcomes, has become a major concern in the world. Among people with COVID-19, severe cases can quickly progress to serious complications, and even death. So, the present study aimed to examine the relationship between the severity of the disease and the outcome in patients afflicted by COVID-19 during hospitalization. METHODS: A total of 653 patients with COVID-19 aged 18 years or older were included from Khorshid hospital in Isfahan, Iran and followed for a mean of 22.72 days (median 23.50; range 1-47). Severe COVID-19 was defined by respiration rate≥30 times/min, oxygen saturation level≤88% in the resting position, and pulse rate≥130/min. The primary outcome was mortality. The secondary outcomes included need for mechanical ventilation and intensive care unit (ICU) admission. RESULTS: During 4233 person-days of follow-up, 49 (7.5%) deaths, 27 (4.1%) invasive ventilation and 89 (13.6%) ICU admissions in hospital were reported. After adjustment for potential confounders, severity of the disease was positively associated with risk of mortality, invasive ventilation and ICU admissions (hazard ratio [HR]: 5.99; 95% CI: 2.85, 12.59; P<0.001, HR: 7.09; 95% CI: 3.24, 15.52; P<0.001 and HR: 4.88; 95% CI: 2.98, 7.98; P<0.001, respectively). In addition, greater age (HR=1.04; 95% CI=1.02-1.07; P=0.002), chronic kidney disease (HR=3.05; 95% CI=1.35, 6.90; P=0.008), blood urea nitrogen (BUN) (HR=1.04; 95% CI=1.03-1.05; P<0.001) and creatinine (HR=1.44; 95% CI=1.26-1.65; P<0.001) were probably significant risk factors for mortality in severe COVID-19 patients. CONCLUSION: More intensive therapy and special monitoring should be implemented for patients with older age, hypertension and kidney disease who are infected with COVID-19 to prevent rapid worsening.