Search

In this unprecedented study in Iran, 30 ambulatory cases of multiple sclerosis (MS), and 30 demographicallv matched normal control (NC) cases were evaluated by a brief cognitive screening test. Beck's Depression Inventory (BDI), and the Mini- Mental State Examination (MMSE). Mean scores of the BDl were significantly different in the MS and NC groups, while the mean MMSE scores were not. At least 11 patients were considered cognitivelv impaired. These cases were older at the. time of testing and of symptom onset. Cognitive dysfunction was significantly more common in patients with secondan progressive course compared to the. cases with remitting - relapsing course. Mean Expanded Disability Status Scale score was higher in the cognitivelv impaired cases. No significant difference was observed in the mean BDl scores of the cognitivelv intact and impaired cases. This studv provides an estimate of the frequency of cognitive dysfunction in ambulatory cases "f MS. and suggests a correlation between much deficits and age sympton onset, disease course, and piiysica! disability but not depression.

This study was conducted to examine effects of resistant starch compared to fructooligosaccharide (FOS) and zinc bacitracin (ZnB), on performance and ileum morphology in broilers. The experiment groups included a control (basal diet with no additive; CON), four groups receiving different levels of resistant starch type 2 (1, 2, 3, and 4% added to basal diet; RS), a group receiving fructooligosaccharide (0.4% in basal diet; FOS), and a group receiving Zinc bacitracin (50 mg/kg basal diet; ZnB). The findings on the day 35 indicated that the groups that received 2% and 3% RS were not significantly different from the FOS group and the ZnB group in terms of feed intake. The largest body weight and the smallest feed conversion ratio was found in the ZnB group (P<0.05). Body weights in the groups treated with 3% and 4% RS were not significantly different from the FOS group. The 3% and 4% RS groups had a greater villus height (P<0.05) and a smaller crypt depth compared to the FOS group. These results demonstrated that while the ZnB group had a better performance than other groups, it seems that adding 3% and 4% RS resulted in a performance similar to adding FOS. [ABSTRACT FROM AUTHOR]

Purpose: To characterize resistance mechanisms to the nucleoside analog 9-β-D-arabinofuranosylguanine (AraG) in the T-cell acute lymphoblastic leukemia cell line MOLT-4 and its AraG-resistant variant.Methods: A gene expression microarray analysis was performed, as well as gene expression and enzyme activity measurements of key enzymes in the activation of AraG. Cytotoxicity of AraG and cross-resistance to other compounds were evaluated using a standard cytotoxicity assay.Results: Gene expression microarray analysis revealed that fetal hemoglobin genes and the multidrug resistance ABCB1 gene, encoding the drug efflux pump P-gp, were the most highly upregulated genes in the resistant cells, while genes traditionally associated with nucleoside analog resistance were not. Fetal hemoglobin and ABCB1 induction can be due to global DNA hypomethylation. This phenomenon was studied using AraG during a period of 4 weeks in MOLT-4 cells and the lung adenocarcinoma cell line A549, leading to up-regulation of hemoglobin gamma and ABCB1 as well as DNA hypomethylation. Inhibiting P-gp in the AraG-resistant MOLT-4 cells led to decreased proliferation, reduced hemoglobin expression, and highly induced ABCB1 expression.Conclusions: We show that AraG can cause hypomethylation of DNA and induce the expression of the fetal hemoglobin gamma gene and the ABCB1 gene. We speculate that the induction of ABCB1/P-gp may occur in order to help with excretion of hemoglobin degradation products that would otherwise be toxic to the cells, and we present data supporting our theory that P-gp may be linked to the induction of hemoglobin. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Essential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by elevated platelet counts and increased risk of thrombosis. Ex vivo data suggest increased platelet reactivity in agreement with the increased thrombosis risk, while in vitro tests often detect decreased platelet activity. The present study aimed to investigate adhesion of ET-platelets in vitro, which is an aspect of platelet function that has been addressed in only a few studies on ET patients. METHODS: The study included 30 ET patients and 14 healthy controls. Platelet adhesion was measured with a static platelet adhesion assay. RESULTS: The main finding was that ET-platelets were more readily activated by adhesion-inducing stimuli in vitro than control platelets. This was particularly evident in elderly patients and when using multiple stimuli, such as surfaces of collagen or fibrinogen combined with addition of adenosine 5'-diphosphate or ristocetin. Such multiple stimuli resulted in adhesion above the control mean +2 standard deviations for approximately 50% of the patients. CONCLUSION: The results are in accordance with the concept of increased platelet activity in ET, but opposite to most other in vitro studies. We suggest that the conditions in the adhesion assay might mimic the in vivo situation regarding the presence of chronic platelet activation. [ABSTRACT FROM AUTHOR]

Activation of nucleoside analogues is dependent on kinases and 5′-nucleotidases and the balance between the activity of these enzymes. The purpose of this study was to analyze deoxycytidine kinase, deoxyguanosine kinase, and 4 different 5′-nucleotidases during cell cycle progression in MOLT-4 cells. The activity of both kinases was cell cycle dependent and increased during proliferation while the activity of cytosolic 5′-nucleotidase I decreased. We could show that the kinase activity was higher than the total nucleotidase activity, which was unchanged or decreased during cell cycle progression. These data may be important in designing modern combination therapy with nucleoside analogues. [ABSTRACT FROM AUTHOR]

Abstract: Our previous data from a human leukemic cell line made resistant to the nucleoside analog (NA) 9-β-D-arabinofuranosylguanine (AraG) revealed a massive upregulation of fetal hemoglobin (HbF) genes and the ABCB1 gene coding for the multidrug resistance P-glycoprotein (P-gp). The expression of these genes is regulated through the same mechanisms, with activation of the p38-MAPK pathway and inhibition of methylation making transcription factors more accessible to activate these genes. We could show that AraG, as well as other NAs, and P-gp substrates could induce global DNA demethylation and induction of Hbγ and P-gp both at the mRNA and protein expression level. We speculate that the expression of HbF prior to drug exposure or in drug-resistant cell lines is a strategy of the cancer to gain more oxygen, and thereby survival benefits. We also believe that P-gp may be induced in order to excrete Hb degradation products from the cells that would otherwise be toxic. By using Hbγ siRNA and pharmacological inhibitors of HbF production we here present a possible relationship between HbF induction and multi-drug resistance in a human leukemia cell line model. [Copyright &y& Elsevier]

Introduction During the last two decades, Bcr-Abl tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myelogenous leukemia (CML), and are now considered standard treatment for this disease. However, TKIs can induce serious hemostatic side effects including cardiovascular disease and bleeding disorders. Blood platelet aggregation and formation of pro-coagulant platelets are important to allow a well-balanced hemostatic response. Therefore, a detailed understanding of what effect different TKIs exert on platelets and hemostasis could help to understand if there are differences of importance to minimize the risk of bleeding complications in treated patients. Aim To investigate how TKIs used in CML (imatinib, dasatinib, nilotinib, bosutinib, and ponatinib) affect platelet activation and hemostasis. Materials and Methods We have developed a multi-parameter six color flow cytometry protocol to study different aspects of platelet function upon activation, e.g. formation of aggregatory (PAC-1-positive) and pro-coagulant (phosphatidylserine-exposing) platelets, exocytosis of alpha- and lysosomal granules and mitochondrial membrane potential.This protocol was performed in presence or absence of TKIs in blood from normal donors and in treated patients. Whole blood aggregometry (Multiplate®), thrombin generation in platelet-rich plasma and in vitro thrombus formation by free oscillation rheometry (ReoRox G2) was further evaluated in some situations. Results At clinically relevant concentrations, dasatinib significantly decreased the formation of procoagulant platelets. Ponatinib induced a slight decrease in formation of procoagulant platelets, whereas bosutinib and nilotinib showed opposite tendencies (n = 7). Dasatinib also decreased platelet aggregation (n = 4-6) and in vitro thrombus formation (n = 3). Thrombin generation was not significantly affected by therapeutic levels of TKIs, whereas higher doses of dasatinib, bosutinib, ponatinib and imatinib significantly changed one or several of the thrombin generation parameters (n = 7-8). Interestingly, large differences in response to the drugs were observed among the healthy donors, especially for dasatinib and bosutinib. Major inter-individual variations were also observed in dasatinib-treated patients, see Figure 1. Fig. 1 A. Dasatinib (70 mg/day)-treated patient showing no pro-coagulant platelet formation (red arrow). B. Dasatinib (80 mg/day)-treated patient with pro-coagulant platelt formation (red arrow). Conclusions Different TKIs show varying potency to affect platelet-based hemostasis. In addition, we found large inter-individual variations in how some drugs affected platelet function. Therefore, we suggest that development of a clinically useful protocol for platelet function testing could help to identify patients more susceptible to adverse drug reactions. Such a protocol could potentially help clinicians to gain insight into the risk of side effects, which could help to choose the most suitable drug for each individual patient. [ABSTRACT FROM AUTHOR]

Diet quality has been associated with mental health, and recently, there has been growing interest in the association between the sustainability of diets and human health. The objective of this cross-sectional study was to explore the relationship between a newly developed dietary index for health and sustainability and psychological disorders among Iranian women. Participants in this cross-sectional study included 479 women living in Tehran with no history of chronic disease. A validated 168-item FFQ was used to assess dietary intake. The World Index for Sustainability and Health was calculated, consisting of four sub-scores: less healthy, healthy, low environmental impact and high environmental impact. Participants' psychological status was assessed using the Depression Anxiety Stress Scale-21. Logistic regression models were used to examine the association between the World Index for Sustainability and Health and psychological disorders. Participant ages ranged from 20 to 50 years, with a mean age of 31·86 (sd 7·68) years. After adjusting for potential confounders (age, energy, BMI, marital status, education, family history of chronic disease, body satisfaction, socio-economic status, physical activity, smoking), women in the highest tertile of the healthy sub-score had significantly lower odds of experiencing depression (OR 0·40; 95 % CI 0·24, 0·67), anxiety (OR 0·45; 95 % CI 0·23, 0·87) and psychological distress (OR 0·46; 95 % CI 0·28, 0·77) compared with the reference group. Similarly, the less healthy sub-score was significantly associated with depression (OR 0·51; 95 % CI 0·32, 0·89), anxiety (OR 0·44; 95 % CI 0·25, 0·78) and psychological distress (OR 0·57; 95 % CI 0·36, 0·90). An inverse association was observed between the low environmental impact sub-score and depression (OR 0·32; 95 % CI 0·19, 0·54), anxiety (OR 0·38; 95 % CI 0·18, 0·76) and psychological distress (OR 0·30; 95 % CI 0·17, 0·51). However, no further significant associations were found with the high environmental impact sub-score, except with depression (OR 0·57; 95 % CI 0·33, 0·96). The healthy and low environmental impact sub-scores of the World Index for Sustainability and Health were found to be inversely associated with depression, anxiety and psychological distress. However, due to the cross-sectional study design, causality cannot be inferred. Further prospective studies are required to validate and expand upon these findings and explore potential mechanisms and alternative explanations, such as reverse causation. While this study suggests that choosing a diet that is both healthy for individuals and sustainable for the environment may be associated with a lower risk of mental health issues among women, more research is needed.

Context: Existing evidence on the relation between folate intake and biomarkers with mortality risk is controversial., Objective: Previous cohort studies were examined regarding folate intake and biomarkers in relation to risk of all-cause, cardiovascular disease- (CVD), and cancer-related mortality through a systematic review and meta-analysis., Data Sources: A systematic search was performed of the PubMed, Scopus, and ISI Web of Science databases up to July 2023., Data Extraction: Prospective cohort studies examining the association of folate biomarkers (in serum, plasma, red blood cells) and intake with risk of all-cause, CVD-, and cancer-related mortality were considered. A random-effects model was applied to combine study-specific risk estimates. Dose-response relations were assessed by 1-stage weighted mixed-effects meta-analysis., Data Analysis: A total of 25 cohorts with 423 304 participants, 36 558 all-cause, 12 662 CVD-, and 2426 cancer-related deaths were included. No significant association was observed between the highest levels of folate biomarkers and all-cause mortality risk (hazard ratio [HR], 0.91; 95% CI, 0.77-1.06; n = 17; I2 = 89.4%; P < .001), CVD-related mortality risk (HR, 0.97; 95% CI, 0.87-1.06; n = 11; I2 = 0.0%; P = .57), and cancer-related mortality risk (HR, 0.85; 95% CI, 0.69-1.05; n = 6; I2 = 57.8%; P = .04) compared with the lowest. Furthermore, each 10 nmol/L increase was marginally related to a 12% reduced all-cause mortality risk but not to CVD- and cancer-related mortality risk. A significant inverse association was found between highest intake of dietary folate and the lowest, and risk of all-cause (HR, 0.87; 95% CI, 0.78-0.96; n = 3; I2 = 63.6%; P = .06) and CVD (HR, 0.77; 95% CI, 0.57-0.93; n = 4; I2 = 80.2%; P = .002) mortality., Conclusions: This meta-analysis revealed a significant inverse relation between dietary folate intake and risk of all-cause and CVD mortality. Such an association was not found in the case of folate biomarkers. Further prospective studies are warranted to confirm these findings., Systematic Review Registration: PROSPERO registration no. CRD42023401700., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: There is a lack of evidence on dietary intake of methyl donor nutrients with metabolic health status and related biomarkers. Thus, this study aimed to assess the relation between methyl donor nutrients intake and metabolic health status with regarding the interactive roles of brain-derived neurotrophic factor (BDNF) and adropin in Iranian adults., Methods: This cross-sectional survey was conducted among 527 Iranian adults (45.7% female) selected by multistage cluster random-sampling method. A validated food frequency questionnaire was used to evaluate participants' dietary intake. Metabolic unhealthy status was defined by Wildman criteria as having ≥ 2 of hyperglycemia, hypertriglyceridemia, hypo-HDL-cholesterolemia, hypertension, chronic inflammation, and insulin resistance. Concentrations of metabolic parameters, BDNF and adropin were determined using fasting blood samples., Results: An inverse association was found between methyl donor nutrients intake and metabolically unhealthy status in multivariable-adjusted model (OR T3 vs. T1  = 0.30; 95%CI: 0.12-0.75). This association was especially significant among overweight/obese adults and was stronger in women. Additionally, consumption of vitamin B6 and choline was separately related to reduced odds of metabolically unhealthy status. Methyl donor intake was not significantly related to low BDNF (OR T3 vs. T1  = 0.93; 95%CI: 0.60-1.44) and adropin (OR T3 vs. T1  = 0.71; 95%CI: 0.44-1.15). However, the interaction between high methyl donor nutrients intake and high BDNF was related to lower odds of metabolically unhealthy status in multivariable-adjusted model (OR MDNS∗BDNF  = 0.27; 95%CI: 0.11-0.67)., Conclusion: Higher intake of methyl donor nutrients, alone and in interaction with BDNF levels, was associated with decreased odds of metabolically unhealthy status in Iranian adults., Competing Interests: Conflict of interest None., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

BCR::ABL1-independent pathways contribute to primary resistance to tyrosine kinase inhibitor (TKI) treatment in chronic myeloid leukemia (CML) and play a role in leukemic stem cell persistence. Here, we perform ex vivo drug screening of CML CD34 + leukemic stem/progenitor cells using 100 single drugs and TKI-drug combinations and identify sensitivities to Wee1, MDM2, and BCL2 inhibitors. These agents effectively inhibit primitive CD34 + CD38 - CML cells and demonstrate potent synergies when combined with TKIs. Flow-cytometry-based drug screening identifies mepacrine to induce differentiation of CD34 + CD38 - cells. We employ genome-wide CRISPR-Cas9 screening for six drugs, and mediator complex, apoptosis, and erythroid-lineage-related genes are identified as key resistance hits for TKIs, whereas the Wee1 inhibitor AZD1775 and mepacrine exhibit distinct resistance profiles. KCTD5, a consistent TKI-resistance-conferring gene, is found to mediate TKI-induced BCR::ABL1 ubiquitination. In summary, we delineate potential mechanisms for primary TKI resistance and non-BCR::ABL1-targeting drugs, offering insights for optimizing CML treatment., Competing Interests: Declaration of interests S.A.A. has received research funding from Incyte. S.M. has received honoraria and research funding from Novartis, Pfizer, and Bristol-Myers Squibb and honoraria from DrenBio (all not related to this study)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Little is known about the relationship between dietary fiber and metabolic health status in adolescents. This study was performed to investigate total dietary fiber intake and metabolic health status in a sample of Iranian adolescents with overweight/obesity. We hypothesized that higher total dietary fiber intake would reduce odds of metabolically unhealthy status. In this cross-sectional study, 203 adolescents (aged 12-18 years) with overweight/obesity were randomly recruited from several educational areas with different socioeconomic statuses using a multistage cluster sampling approach. Dietary intakes were evaluated by a validated food frequency questionnaire. Demographic, anthropometric, and cardiometabolic data were gathered through standard methods. Adolescents were categorized as having either metabolically healthy overweight/obesity or metabolically unhealthy overweight/obesity (MUO) phenotypes according to the International Diabetes Federation (IDF) and IDF/Homeostasis Model Assessment Insulin Resistance (HOMA-IR) criteria. Subjects had mean age of 13.97 (years) and mean fiber intake of 19.5 (g/d). After considering potential confounders, adolescents with the highest fiber intake, compared with the lowest intake, had decreased odds of MUO based on IDF (odds ratio [OR] = 0.14; 95% confidence interval [CI], 0.04-0.46) and IDF/HOMA-IR (OR = 0.16; 95% CI, 0.04-0.56) definitions. Also, each additional unit of total dietary fiber intake (1 g/d) was associated with lower chance of MUO phenotype considering IDF and IDF/HOMA-IR criteria. Individuals with higher intakes of dietary fiber were also less likely to have hyperglycemia (in fully adjusted model: OR = 0.17; 95% CI, 0.06-0.52). We found that consumption of total dietary fiber was inversely associated with odds of MUO among Iranian adolescents. Further prospective studies are required for confirming our results., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Little is known about the relationship between dietary intake of phytochemicals with metabolic health status and underlying mechanisms., Objectives: Little is known about the relationship between dietary intake of phytochemicals with metabolic health status and underlying mechanisms. We hypothesized that dietary phytochemical index (DPI) improves metabolic health status by ameliorating serum concentrations of brain-derived neurotrophic factor (BDNF) and adropin., Methods: A cross-sectional study was performed in 527 adults (286 males and 241 females). The dietary intakes of participants were collected by a 168-item food frequency questionnaire, and DPI was estimated as a percentage of energy intake derived from phytochemical-rich foods. Anthropometric variables, blood pressure, glycemic and lipid profiles, and biochemical variables were assessed. The metabolically unhealthy (MU) phenotype was determined based on the definition presented by Wildman et al., Results: The MU phenotype was identified in 51.4% of male and 32.0% of female participants. Participants in the third tertile of DPI had 59% lower odds of MU than those in the first tertile (OR: 0.41; 95% CI: 0.19, 0.87) after considering potential confounders. Stratified analysis by sex and body mass index indicated that DPI was inversely related to MU phenotype in females (OR: 0.28; 95% CI: 0.08, 0.97) and normal-weight individuals (OR: 0.11; 95% CI: 0.02, 0.62). DPI was also inversely associated with hyperglycemia, hypertriglyceridemia, and chronic inflammation. Nonsignificant reduced odds of low BDNF (OR: 0.87; 95% CI: 0.42, 1.84) and adropin (OR: 0.75; 95% CI: 0.31, 1.79) were observed in individuals in the top tertile of DPI compared with those in the bottom tertile., Conclusions: This study showed that individuals with higher dietary intake of phytochemicals had lower odds of MU, particularly females and normal-weight individuals. No significant relationship was observed between serum BDNF and adropin with phytochemical intake., (© 2024 The Authors.)

Background: There is a lack of data regarding the Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet and metabolic health., Objectives: This study assessed the relation between MIND diet and metabolic health status relative to serum brain-derived neurotrophic factor (BDNF) concentrations., Methods: This was a cross-sectional study of 527 adults (286 males and 241 females) recruited from 20 schools in 6 different educational districts of Isfahan, Iran. Dietary intakes of participants were collected by a validated 168-item food frequency questionnaire, and MIND diet score was estimated. Anthropometric indices, blood pressure, biochemical parameters, and BDNF concentrations were assessed for all participants. The metabolically unhealthy (MU) phenotype was determined based on blood pressure, glycemic and lipid profiles, chronic inflammation, and insulin resistance., Results: The frequency of MU phenotype among obese/overweight and normal-weight individuals was 79.5 % and 20.5 %, respectively. After adjustment for confounders, individuals in the top tertile of the MIND diet scores had 58 % lower odds of having the MU phenotype than individuals in the bottom tertile (odds ratios [ORs]: 0.42; 95 % confidence interval [CI]: 0.20, 0.90). In the fully adjusted model, females and normal-weight individuals had 81 % (OR: 0.19; 95 % CI: 0.04, 0.83) and 89 % (OR: 0.11; 95 % CI: 0.02, 0.69) lower chance of developing the MU phenotype, respectively. In addition, significant inverse associations between adherence to the MIND diet and high-blood pressure and hypertriglyceridemia were found. No significant association was found between adherence to MIND diet and odds of low BDNF concentrations., Conclusions: Adherence to MIND diet is inversely associated with odds of MU phenotype, especially among women and normal-weight individuals. BDNF concentration is not associated with MIND diet and MU status., (© 2024 The Authors.)

Carotenoids appear to have anticancer effects. Prospective evidence for the relation between serum carotenoids and breast cancer is controversial. The present systematic review and meta-analysis aimed to investigate the link between circulating carotenoids and the risk of breast cancer. We performed a systematic search of PubMed, Scopus, and Web of Science up to 30 November, 2022. Prospective studies on adults aged ≥18 y that have reported risk estimates for the association between circulating carotenoids and breast cancer risk were considered. Study quality was assessed using the Newcastle-Ottawa Scale. A random-effects model was used for combining studies' risk estimates. Dose-response relations were explored through a 1-stage random-effects model. Fifteen publications (17 nested case-control studies and 1 cohort study) with 20,188 participants and 7608 cases were included. We observed an inverse association between the highest level of circulating total carotenoids (relative risk [RR]: 0.76; 95% confidence interval [CI]: 0.62, 0.93; n = 8), α-carotene (RR: 0.77; 95% CI: 0.68, 0.87; n = 13), β-carotene (RR: 0.80; 95% CI: 0.65, 0.98; n = 15), β-cryptoxanthin (RR: 0.85; 95% CI: 0.74, 0.96; n = 11), lycopene (RR: 0.86; 95% CI: 0.76, 0.98; n = 13), and lutein (RR: 0.70; 95% CI: 0.52, 0.93; n = 6) and the risk of breast cancer compared with the lowest level. Additionally, each 10 μg/dL of total carotenoids, α-carotene, β-carotene, and β-cryptoxanthin was associated with 2%, 22%, 4%, and 10% lower risk of breast cancer, respectively. This relationship was stronger at lower levels of total carotenoids and β-cryptoxanthin. The certainty of evidence was rated from very low to low. Most studies were performed among Western nations, which should be acknowledged for extrapolation of findings. Total circulating carotenoids, α-carotene, β-carotene, β-cryptoxanthin, lycopene, and lutein seem to be related to a decreased risk of breast cancer. Our findings could have practical importance for public health. This study was registered at PROSPERO as CRD42023434983., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Metabolic disturbances are of major health concerns in the world. In addition to their high prevalence, these disorders have substantial roles in developing other physical and mental diseases. Diet could have a considerable influence on managing the progression of these conditions and their consequent health-related effects. The aim of the 'Diet in relation to Metabolic, sleep and psychological health Status' Project is to explore the association of nutrition with metabolic, sleep and mental health, considering potential mediators including brain-derived neurotrophic factor (BDNF) and adropin., Methods and Analysis: This cross-sectional study will be conducted on adults (20-65 years) working in schools of Isfahan, Iran. A multistage cluster random sampling method will be used to select participants. Anthropometric, body composition and biochemical values including fasting blood glucose, lipid profile, 25-hydroxy vitamin D, insulin, BDNF, adropin, malondialdehyde, superoxide dismutase, glutathione peroxidase, uric acid, creatinine and C reactive protein will be measured for each participant. National Cholesterol Education Program and Adult Treatment Panel III will be considered to define metabolic syndrome. Diet will be assessed through a validated Food Frequency Questionnaire. Furthermore, sleep status, mental health, quality of life, physical activity and demographic status of individuals will be assessed by validated questionnaires. The collected data will be analysed using appropriate statistical methods., Ethics and Dissemination: The study protocol was approved by the local Ethics Committee of Isfahan University of Medical Sciences. All participants will provide written informed consent. Dissemination will be through conference presentations and publications in peer-reviewed journals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The associations of high potential insulinogenic foods with metabolic health (MH) status and brain-derived neurotrophic factor (BDNF) and adropin were not investigated quite enough. We examined the relationship between dietary insulin load (DIL) and dietary insulin index (DII) with MH and serum levels of BDNF and adropin among Iranian adults. This cross-sectional investigation accomplished among 527 Iranian middle-aged adults (54.3% men). Dietary information was obtained by a validated food frequency questionnaire. Anthropometric indices and blood pressure were assessed. For measuring lipid and glycemic profile and serum levels of BDNF and adropin, blood samples were assembled after 12 h of fasting. MH was defined based on lipid and glycemic profile, high blood pressure, insulin resistance and chronic inflammation. After adjustments all confounders, participants in the highest tertile of DII compared to the lowest one had a 115% increased odds for metabolic unhealthy (MU) profile (OR T3 vs. T1  = 2.15, 95% CI 1.03-4.49). However, DIL was not related to MU. Higher DII was additionally associated with high blood pressure, in maximally-adjusted model (OR T3 vs. T1  = 3.57, 95% CI 1.61-7.92). Moreover, moderate DIL was significantly associated with hypertriglyceridemia (OR T2 vs. T1  = 2.56, 95% CI 1.01-6.45). Each tertile increase in DII or DIL was not significantly associated with serum BDNF or adropin values. Greater DII was associated with higher chance of MU and hypertension in Iranian adults; but no association was found between DIL and metabolic health. DIL or DII was not related to circulating BDNF or adropin. To confirm these findings, additional prospective investigations are required., (© 2023. The Author(s).)

Nutrient pattern analysis is an easy way to compare nutrient intakes across different nations due to the universality of nutrients nature. The purpose of this study was to examine the relationship between dietary nutrient patterns (NPs) and circulating 25(OH)D concentrations with sleep duration and sleep quality among Iranian adults. We used a multistage cluster random sampling method to enroll 535 adults in this cross-sectional investigation. A validated food frequency questionnaire was applied to evaluate typical dietary intakes. Fasting blood samples were obtained to determine levels of circulating 25(OH)D. Sleep characteristics were assessed using the Pittsburgh Sleep Quality Index (PSQI). Participants had a mean age of 42.57 years and 51.2% of them had insufficient or deficient levels of serum vitamin D. Three NPs were identified: "high animal protein", "high vegetable" and "high carbohydrate". After adjustments for potential confounders, no significant associations were observed between "high animal protein" pattern and short sleeping or sleep quality. Greater adherence to "high vegetable" NP was associated with lower odds of short sleeping (OR 0.24; 95% CI 0.10, 0.54) and poor sleep quality (OR 0.45; 95% CI 0.20, 1.05). Stratified analysis revealed that these associations were stronger in normal-weight participants. Greater adherence to "high carbohydrate" NP, on the other hand, was connected to higher odds of short sleeping (OR 2.83; 95% CI 1.20, 6.72). Low adherence to "high vegetable" pattern and vitamin D insufficiency/deficiency were jointly associated with increased odds of short sleeping (OR 3.42, 95% CI 1.42, 6.64). High adherence to pattern comprising mainly of vegetable nutrients was associated with a reduced likelihood of being short sleepers and having poor sleep quality in Iranian adults, especially among those with a normal weight. Lower adherence to vegetable NP and insufficient/deficient vitamin D levels were synergistically associated with greater likelihood of being short sleepers. Greater adherence to carbohydrate NP was associated with an increased likelihood of short sleeping., (© 2023. Springer Nature Limited.)

Background: The present study aimed to investigate the association between dietary linoleic acid (LA) intake and breast cancer in women., Methods: In this population-based case-control study, we enrolled 350 pathologically confirmed breast cancer cases and 700 controls which were matched with cases in terms of age and socioeconomic status. Dietary intakes were assessed using a 106-item Willett-format semi-quantitative dish-based food frequency questionnaire (DS-FFQ). Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated., Results: A significant inverse association was found between LA intake and odds of breast cancer (OR: 0.41, 95% CI: 0.30-0.56). After adjusting for potential confounders, women in the highest tertile of dietary LA intake were 48% less likely to have breast cancer compared with those in the lowest tertile (OR: 0.52, 95% CI: 0.28-0.95). Such a significant inverse association was also seen among normal-weight women (OR: 0.29, 95% CI: 0.14-0.63), and premenopausal women (OR: 0.15, 95% CI: 0.02-0.95)., Conclusion: The findings of current study provide evidence for a protective role of LA against breast cancer particularly among normal-weight and premenopausal women. Prospective studies are needed to confirm this association., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s).)

Context: Although some studies have examined the connection between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and preeclampsia (PE) risk, the results were inconsistent., Objective: A dose-response meta-analysis on epidemiologic investigations was conducted to evaluate the relation of 25(OH)D concentration and PE., Data Source: Electronic databases, including Scopus, MEDLINE (PubMed), the Institute for Scientific Information, Embase, and Google Scholar, were comprehensively search until July 2021., Data Extraction: A total of 65 observational studies evaluating the link between circulating 25(OH)D concentrations and PE were included. The body of evidence was assessed by the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach., Data Analysis: Combining 32 effect sizes from 32 prospective studies with 76 394 participants revealed that highest vs lowest circulating 25(OH)D concentrations was significantly related to a 33% reduced risk of PE (relative risk [RR], 0.67; 95%CI, 0.54-0.83). Subgroup analysis by study design revealed that PE risk has significantly decreased in cohort and case-cohort studies (RR, 0.72; 95%CI, 0.61-0.85), and a slight decline was found in nested case-control studies (RR, 0.62; 95%CI, 0.38-1.02). Dose-response analysis in 27 prospective studies with 73 626 participants illustrated that each 10 ng/mL increment in circulating 25(OH)D concentration led to a 14% reduced incidence of PE (RR, 0.86; 95%CI, 0.83-0.90). A U-shaped significant association in nonlinear dose-response analysis was found between 25(OH)D and PE. A significant inverse association was also found between highest vs lowest circulating 25(OH)D concentration and PE in 32 nonprospective studies with 37 477 participants (odd ratio, 0.37; 95%CI, 0.27-0.52). This inverse association was significant in almost all subgroups, based on different covariates., Conclusion: This meta-analysis of observational investigations showed blood 25(OH)D levels were negatively related to PE risk, in a dose-response manner., Systematic Review Registration: PROSPERO registration no. CRD42021267486., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Data on the association between Mediterranean diet, sleep and brain-derived neurotrophic factor (BDNF) were limited in Middle Eastern populations. We examined the association between Mediterranean dietary pattern with sleep quality/quantity, and serum BDNF in Iranian adults. This cross-sectional study was performed among 535 middle-aged adults (54% men), selected by multistage cluster random sampling method. The Pittsburgh sleep quality index and a validated food frequency questionnaire were used to assess sleep quality, sleep quantity, and Mediterranean diet score (MDS). Twelve-hour fasting blood samples were taken to evaluate serum BDNF values. Participants in the highest tertile of MDS, in comparison to those in the lowest tertile, had lower odds of having short sleep (OR = 0.44, 95%CI: 0.21-0.91) and poor sleep quality (OR = 0.48, 95%CI: 0.22-0.96), after adjustment for potential confounders. Among specific domains of sleep quality, lower odds of subjective sleep quality, sleep latency, and daytime dysfunction were associated with increased MDS. Higher adherence to MDS among individuals with overweight or obesity reduced the odds of having short sleep; this relation was not seen among individuals with normal weight. In contrast, the association between sleep quality and the MDS was significant in individuals with normal weight, but not those with overweight or obesity. Participants with higher adherence to MDS had lower odds for low BDNF values; however, this relation was not statistically significant. Overall, Iranian adults with a higher adherence to MDS had considerably lower odds of having short sleep and poor sleep quality. BDNF would not be an intermediate molecule for this connection., (© 2023. Springer Nature Limited.)

Previous studies have rarely investigated dietary phytochemicals consumption in relation to metabolic health of adolescents. The current study was performed to investigate dietary phytochemical index (DPI) in relation to metabolic health status in overweight and obese adolescents. This cross-sectional study was conducted among 203 adolescents with overweight or obesity. Dietary intakes of participants were obtained through a validated 147-item food frequency questionnaire. DPI was calculated [(dietary energy derived from phytochemical-rich foods (kcal)/total daily energy intake (kcal)) ⨯100]. Glycemic and lipid profiles, blood pressure, and anthropometric indices were also measured. A metabolically unhealthy overweight/obesity (MUO) profile was determined based on the International Diabetes Federation (IDF) and IDF/Homeostasis Model Assessment Insulin Resistance (HOMA-IR) definitions. Study subjects had a mean age of 13.98 years and 50.2% of them were girls. According to IDF and IDF/HOMA-IR criteria, 38.9% (37 boys, and 42 girls) and 33% (35 boys, and 32 girls) of the study participants were respectively MUO. According to IDF and IDF/HOMA-IR definitions, adolescents in the third DPI tertile had respectively 61% (maximally-adjusted OR = 0.39, 95%CI 0.16-0.91) and 67% (maximally-adjusted OR = 0.33, 95%CI 0.13-0.83) lower odds of being MUO, compared to the first tertile. Stratified analysis by sex indicated that DPI was inversely related to MUO phenotype based on IDF criteria in girls (maximally-adjusted OR = 0.25, 95%CI 0.06-0.98), but not in boys. The current study found that adolescents with a higher dietary intake of phytochemicals have lower odds of being MUO, particularly among girls. However, further large-scale prospective cohort studies are required to confirm this finding., (© 2023. The Author(s).)

Background: Several studies have explored the association between Mediterranean diet and frailty, but reported inconsistent results. This systematic review and dose-response meta-analysis summarized the existing evidence on the relationship between Mediterranean diet and risk of frailty and pre-frailty in elderly adults., Methods: A systematic search on MEDLINE (PubMed), Scopus, Institute for Scientific Information (ISI) Web of Science and Google Scholar was conducted up to January 2023. Study selection and data extraction were performed by two reviewers working in parallel. Epidemiologic studies reporting relative risks (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) for frailty/pre-frailty in relation to Mediterranean diet (as a priori dietary pattern) were considered. The overall effect size was determined using a random effects model. The body of evidence was assessed by the GRADE approach., Results: A total of 19 studies (12 cohorts and 7 cross-sectionals) were included. In cohort studies (89,608 participants/ 12,866 cases), the highest versus lowest category of Mediterranean diet was inversely associated with frailty (RR: 0.66; 95%CI: 0.55, 0.78; I 2 :52.4%, P Q-test =0.02). This association was also significant in cross-sectional studies with 1093 cases among 13,581 participants (OR: 0.44; 95%CI: 0.28, 0.70; I 2 :81.8%, P Q-test <0.001). Moreover, each 2-point increase in Mediterranean diet score was related to decreased risk of frailty in cohort (RR: 0.86; 95%CI: 0.80, 0.93) and cross-sectional (OR: 0.79; 95%CI: 0.65, 0.95) studies. Nonlinear association showed a decreasing slope in curve, sharper at high scores for cohort studies and a steadily reduction for cross-sectional studies. The certainty of the evidence was graded as high in both cohort and cross-sectional studies. Combining 4 effect sizes of 4 studies (12,745 participants/ 4363 cases), the highest adherence to Mediterranean diet was linked to a lower risk of pre-frailty, as well (pooled OR: 0.73; 95%CI: 0.61, 0.86; I 2 :40.9%, P Q-test =0.17)., Conclusion: Adherence to Mediterranean diet is inversely associated with risk of frailty and pre-frailty in older adults and thus, has a considerable impact on health of this population., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Randomized trials of venetoclax plus anti-CD20 antibodies as first-line treatment in fit patients (i.e., those with a low burden of coexisting conditions) with advanced chronic lymphocytic leukemia (CLL) have been lacking., Methods: In a phase 3, open-label trial, we randomly assigned, in a 1:1:1:1 ratio, fit patients with CLL who did not have TP53 aberrations to receive six cycles of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) or 12 cycles of venetoclax-rituximab, venetoclax-obinutuzumab, or venetoclax-obinutuzumab-ibrutinib. Ibrutinib was discontinued after two consecutive measurements of undetectable minimal residual disease or could be extended. The primary end points were undetectable minimal residual disease (sensitivity, <10 -4 [i.e., <1 CLL cell in 10,000 leukocytes]) as assessed by flow cytometry in peripheral blood at month 15 and progression-free survival., Results: A total of 926 patients were assigned to one of the four treatment regimens (229 to chemoimmunotherapy, 237 to venetoclax-rituximab, 229 to venetoclax-obinutuzumab, and 231 to venetoclax-obinutuzumab-ibrutinib). At month 15, the percentage of patients with undetectable minimal residual disease was significantly higher in the venetoclax-obinutuzumab group (86.5%; 97.5% confidence interval [CI], 80.6 to 91.1) and the venetoclax-obinutuzumab-ibrutinib group (92.2%; 97.5% CI, 87.3 to 95.7) than in the chemoimmunotherapy group (52.0%; 97.5% CI, 44.4 to 59.5; P<0.001 for both comparisons), but it was not significantly higher in the venetoclax-rituximab group (57.0%; 97.5% CI, 49.5 to 64.2; P = 0.32). Three-year progression-free survival was 90.5% in the venetoclax-obinutuzumab-ibrutinib group and 75.5% in the chemoimmunotherapy group (hazard ratio for disease progression or death, 0.32; 97.5% CI, 0.19 to 0.54; P<0.001). Progression-free survival at 3 years was also higher with venetoclax-obinutuzumab (87.7%; hazard ratio for disease progression or death, 0.42; 97.5% CI, 0.26 to 0.68; P<0.001), but not with venetoclax-rituximab (80.8%; hazard ratio, 0.79; 97.5% CI, 0.53 to 1.18; P = 0.18). Grade 3 and grade 4 infections were more common with chemoimmunotherapy (18.5%) and venetoclax-obinutuzumab-ibrutinib (21.2%) than with venetoclax-rituximab (10.5%) or venetoclax-obinutuzumab (13.2%)., Conclusions: Venetoclax-obinutuzumab with or without ibrutinib was superior to chemoimmunotherapy as first-line treatment in fit patients with CLL. (Funded by AbbVie and others; GAIA-CLL13 ClinicalTrials.gov number, NCT02950051; EudraCT number, 2015-004936-36.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: Little is known about the association of plant-based diet indices with metabolic syndrome (MetS) and its novel predictive biomarkers, including the atherogenic index of plasma (AIP) and adropin. We aimed to investigate the association of plant-based diets with adropin, atherogenic index of plasma, and MetS and its components in adults., Methods: The present population-based cross-sectional study was conducted on a representative sample of adults aged 20-60 years in Isfahan, Iran. Dietary intake was obtained through a validated 168-item semi-quantitative food frequency questionnaire (FFQ). Peripheral blood was obtained after an overnight fast of at least 12 h from each participant. MetS was identified based on the Joint Interim Statement (JIS). AIP was calculated as a logarithmically transformed ratio of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-c), and serum levels of adropin were measured by an ELISA kit., Results: A total of 28.7% of subjects had MetS. No significant association was found between the overall plant-based diet index (PDI) and the healthful plant-based diet index (hPDI) with MetS. However, a non-linear association was observed between hPDI and MetS. Subjects in the third quartile of the unhealthful plant-based diet index (uPDI) had higher odds of MetS compared to the first quartile (OR: 2.39; 95% CI: 1.01, 5.66). The highest quartile of PDI (OR: 0.46; 95% CI: 0.21, 0.97) and the third quartile of hPDI (OR: 0.40; 95% CI: 0.18, 0.89) were associated with decreased odds of having high-risk AIP compared to the first quartile, after adjusting for potential confounders. No linear association was found between quartiles of plant-based diet indices and serum levels of adropin., Conclusion: Plant-based diet index (PDI) and hPDI were not associated with the prevalence of MetS in adults, while moderate adherence to uPDI increased the prevalence of MetS. In addition, high adherence to PDI and moderate adherence to hPDI were associated with decreased odds of high-risk AIP. No significant association was found between plant-based diet indices and serum adropin levels. To confirm these findings, further studies with prospective designs are warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer SN declared a shared affiliation with the author KL to the handling editor at the time of review., (Copyright © 2023 Shahdadian, Saneei, Lotfi, Feizi, Askari and Safavi.)

Existing evidence examining the relation between egg consumption and metabolic health of overweight/obese adolescents is scarce. We examined the association between egg consumption and metabolic status in Iranian overweight/obese adolescents. Using multistage cluster random sampling approach, overweight/obese adolescents (n = 203) with ages from 12 to 18 years old were selected for the present cross-sectional study. A validated 147-item food frequency questionnaire was adopted to determine usual dietary intakes. Blood pressure and anthropometric data and were assessed, and levels of lipid profile, insulin, and glucose were measured by collecting fasting blood samples. Participants were classified into metabolically healthy obese (MHO) or metabolically unhealthy obese (MUO) based on two methods of International Diabetes Federation (IDF) and the combination of IDF with Homeostasis Model Assessment Insulin Resistance (HOMA-IR). In total, 67 (33.0%) and 79 (38.9%) adolescents were classified as MUO based on IDF/HOMA and IDF definitions, respectively. Considering IDF criteria, the highest intake of egg was related to decreased chance of MUO, in crude (OR 0.22; 95% CI 0.10-0.48) and maximally-adjusted model (OR 0.25; 95% CI 0.10-0.59). Considering IDF/HOMA-IR criteria, similar results were obtained (crude model: OR 0.24; 95% CI 0.11-0.52; fully-adjusted model: OR 0.28; 95% CI 0.11-0.69). Stratified analyses found stronger relation among boys (vs. girls) and overweight (vs. obese) individuals. In conclusion, higher egg consumption was negatively related to decreased chance of being MUO in overweight/obese adolescents, especially in boys and overweight individuals, regardless of MUO definitions. Prospective studies are required to support our results., (© 2023. The Author(s).)