The effect of crocin-selenium nanoparticles on the cognition and oxidative stress markers of multiple sclerosis patients: a randomized triple-blinded placebo-controlled clinical trial.

The prevalence of cognitive impairment in multiple sclerosis (MS) patients is estimated to be approximately 40-60%. There is an increasing body of evidence regarding the impact of both selenium and crocin as antioxidant agents on cognitive function. In the present study, for the first time, we investigated the effect of crocin-selenium nanoparticles (Cor@SeNs) on cognitive function and oxidative stress markers in MS patients. A triple-blind randomized clinical trial was conducted among 60 MS patients. The participants were randomly divided in a 1:1 ratio to either the Cor@SeNs or placebo group, employing block randomization. During the course of 12 weeks, the participants received Cor@SeNs capsules, containing 5.74 mg crocin and 55 mcg Selenium, or placebo capsules. Cognition assessed using the Persian version of the Brief International Cognitive Assessment for MS (BICAMS) battery. Serum levels of total antioxidant capacity (TAC), glutathione reductase (GR) activity and malondialdehyde (MDA) determined by colorimetric kits. Data analysis was performed in SPSS, version 26. P < 0.05 was considered as the significant range. The mean ± SD of TAC change was 0.03 ± 0.07 mM vs. - 0.03 ± 0.09 mM in intervention and placebo groups, respectively (Time × group effect P: 0.01; effect size: 0.10). The time effect of intervention on the California Verbal Learning Test second edition (CVLT-II) (P < 0.01; effect size: 0.29), CVLT-II-delay (P < 0.01; effect size: 0.29), and the Symbol Digit Modalities Test (SDMT) (P < 0.01; effect size: 0.18) was increasing and significant. In addition, the time effect of intervention on GR activity was significant and decreasing in both groups (P < 0.01; effect size: 0.20). Our results suggested a significant effect of the Cor@SeNs intervention in improving TAC. We also observed a significant improvement in cognitive function in both groups during our study. However, although not statistically significant, a higher amount of change in cognitive function and serum antioxidant markers was noted in the Cor@SeNs group compared to the placebo group. This is the first study on this nano product with low dose of selenium and crocin. More investigations with longer duration and varied doses are suggested.

Increased serum prolactin level may indicate more migraine attack frequency.

OBJECTIVES: Migraine is a common, multifactorial disorder. The exact pathomechanism of migraine remains unclear. Studies have revealed changes in serum prolactin (PRL) levels in relation to migraine, although the results have been inconsistent. The present case-control study assessed the serum level of prolactin in migraine patients. MATERIALS AND METHODS: In this case-control study, participants were divided into chronic migraine (CM; n = 39), episodic migraine in ictal (during an attack), and interictal (between attacks) phases (n = 63, n = 37, respectively) along with 30 age- and sex-matched headache-free controls. After obtaining demographic, anthropometric data, and headache characteristics, blood samples were gathered and analyzed to evaluate the serum levels of prolactin (ng/mL). RESULTS: A significant difference was observed between the control, CM, and ictal EM, and interictal EM groups. The mean ± SD serum prolactin levels of the chronic migraineurs (1.82 ± 0.94) and those with ictal EM (1.93 ± 1.70) were comparable and were significantly higher than for interictal EM patients (0.82 ± 0.46) and the headache-free control subjects (0.49 ± 0.15; p < .001). Although the mean serum concentration of prolactin for the interictal EM group tended to be higher than for control individuals, this difference was not statistically significant. The Spearman's correlation test also showed significant correlations between the serum prolactin levels and the number of headaches days among migraineurs. CONCLUSION: The findings suggest that there might be an association between increased prolactin concentrations and migraine headache induction and progression. Further detailed and well-designed studies are needed to confirm the importance of serum prolactin levels in the pathogenesis of migraine headaches.

Association of body mass index and physical activity with fatigue, depression, and anxiety among Iranian patients with multiple sclerosis.

Introduction: Depression, fatigue, and anxiety are three common clinical comorbidities of multiple sclerosis (MS). We investigated the role of physical activity (PA) level and body mass index (BMI) as modifiable lifestyle factors in these three comorbidities. Methods: A cross-sectional study was conducted in the MS specialist clinic of Sina Hospital, Tehran, Iran. Demographic and clinical data were collected. BMI was categorized in accordance with the WHO's standard classification. Physical activity (PA) level and sitting time per day were obtained using the short form of the International Physical Activity Questionnaire (IPAQ-SF). Fatigue, anxiety, and depression scores were measured using the Persian version of the Fatigue Severity Scale (FSS), Beck Anxiety Inventory (BAI), and Beck's Depression Inventory II (BDI-II) questionnaires, respectively. The correlation between the metabolic equivalent of tasks (MET), BMI, and daily sitting hours with depression, anxiety, and fatigue were checked using the linear regression test. The normal BMI group was considered a reference, and the difference in quantitative variables between the reference and the other groups was assessed using an independent sample t-test. Physical activity was classified with tertiles, and the difference in depression, anxiety, and fatigue between the PA groups was evaluated by a one-way ANOVA test. Results: In total, 85 MS patients were recruited for the study. The mean ± SD age of the participants was 39.07 ± 8.84 years, and 72.9% (n: 62) of them were female. The fatigue score was directly correlated with BMI (P: 0.03; r: 0.23) and sitting hours per day (P: 0.01; r: 0.26) and indirectly correlated with PA level (P < 0.01; r: -0.33). Higher depression scores were significantly correlated with elevated daily sitting hours (P: 0.01; r: 0.27). However, the correlation between depression with PA and BMI was not meaningful (p > 0.05). Higher anxiety scores were correlated with BMI (P: 0.01; r: 0.27) and lower PA (P: 0.01; r: -0.26). The correlation between anxiety and sitting hours per day was not significant (p > 0.05). Patients in the type I obesity group had significantly higher depression scores than the normal weight group (23.67 ± 2.30 vs. 14.05 ± 9.12; P: 0.001). Fatigue (32.61 ± 14.18 vs. 52.40 ± 12.42; P: <0.01) and anxiety (14.66 ± 9.68 vs. 27.80 ± 15.48; P: 0.01) scores were significantly greater among participants in the type II obesity group in comparison with the normal weight group. Fatigue (P: 0.01) and anxiety (P: 0.03) scores were significantly different in the three levels of PA, but no significant difference was found in the depression score (P: 0.17). Conclusion: Our data suggest that a physically active lifestyle and being in the normal weight category are possible factors that lead to lower depression, fatigue, and anxiety in patients with MS.

The prevalence of headache disorders in children and adolescents in Iran: a schools-based study.

BACKGROUND: While the Global Burden of Disease study reports headache disorders as the third-highest cause of disability worldwide, the headache data in this study largely come from adults. This national study in Iran, the first of its type in the Eastern Mediterranean Region, was part of a global schools-based programme within the Global Campaign against Headache contributing data from children (6-11 years) and adolescents (12-17 years). METHODS: We followed the generic protocol for the global study. In a cross-sectional survey, self-completed structured questionnaires were administered to pupils within their classes in 121 schools selected from across the country to be representative of its diversities. Headache diagnostic questions were based on ICHD-3 criteria but for the inclusion of undifferentiated headache. RESULTS: Of 3,357 potential participants, 3,244 (children 1,308 [40.3%], adolescents 1,936 [59.7%]; males 1,531 [47.2%], females 1,713 [52.8%]) satisfactorily completed the questionnaire. Children and males were therefore somewhat under-represented, with a participating proportion of 96.6%. Gender- and age-adjusted 1-year prevalence of any headache was 65.4%, of migraine 25.2%, of tension-type headache 12.7%, of undifferentiated headache 22.1%, of all headache on ≥15 days/month 4.1%, and of probable medication-overuse headache 1.1%. All headache types except undifferentiated headache were more prevalent among adolescents than children; probable medication-overuse headache increased five-fold between childhood and adolescence. CONCLUSIONS: Headache disorders are common in children and adolescents in Iran, with undifferentiated headache accounting for over one third of cases. The increasing prevalence of probable medication-overuse headache with age is concerning. These findings are of importance to health and educational policies in Iran.

Dietary diversity score (DDS) and odds of colorectal cancer and adenoma: a case-control study.

Despite mounting evidence that dietary factors might have a protective role against risk of cancer, few studies have assessed the relationship between diet diversity with colorectal cancer (CRC) and colorectal adenoma (CRA). Thus, we examined the relationship between dietary diversity score (DDS) and the odds of CRC and CRA. Overall, 129 CRC diagnosed patients, 130 CRA diagnosed cases and 240 healthy hospitalised controls were studied. DDS was calculated based on information on the usual diet that was assessed by a valid and reliable food frequency questionnaire (FFQ). Multivariate logistic regression was used to estimate the relationship between DDS and odds of colorectal cancer and adenoma. After adjusting for potential confounders, the diversity of grains is associated with the increased odds of CRC (ORgrains: 2·96 (1·05-8·32); P = 0·032), while the diversity of vegetables and fruits are associated with decreased odds of CRC (ORvegetables: 0·31 (0·16-0·62); P = 0·001, ORfruits: 0·37 (0·23-0·61); P < 0·001). The diversity of vegetables, fruits and dairy are inversely associated with odds of CRA (ORvegetables: 0·41 (0·21-0·78); P = 0·007, ORfruits: 0·58 (0·36-0·93); P = 0·021, ORdairies: 0·56 (0·37-0·83); P = 0·004). Also, higher DDS was related to decreased odds of both CRC (OR: 0·41 (0·23-0·72); P for trend = 0·002) and CRA (OR: 0·36 (0·21-0·65); P for trend = 0·001). Our results indicated that higher dietary diversity and particularly a diet varied in fruits and vegetables may reduce the odds of CRC and CRA. Also, the consumption of dairy products may decrease the odds of CRC, whereas the consumption of grains may increase the odds of CRC.

Assessment of peripheral biomarkers potentially involved in episodic and chronic migraine: a case-control study with a focus on NGF, BDNF, VEGF, and PGE2.

BACKGROUND: Several inflammatory and vascular molecules, and neurotrophins have been suggested to have a possible role in the development of migraine. However, pathophysiological events leading to migraine onset and transformation of episodic migraine (EM) to chronic migraine (CM) are not fully understood. Thus, we aimed to assess peripheral levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2) in EM and CM patients, and controls. METHODS: From September 2017 to June 2020, 89 subjects were enrolled in a case-control study; 23 and 36 EM and CM patients, respectively, and 30 age and sex-matched controls. Demographic data and medical history were obtained from all patients. Headache characteristics were recorded at baseline visit and ensuing 30 days for persons with migraine disease. Serum levels of NGF, BDNF, VEGF, and PGE2 were measured once for controls and EM and CM patients, and adjusted for age, sex, and body mass index. RESULTS: Serum levels of NGF were significantly lower in EM patients compared to controls and CM patients (P-value=0.003 and 0.042, respectively). Serum levels of BDNF were significantly lower in EM and CM patients as opposed to controls (P-value<0.001), but comparable between EM and CM patients (P-value=0.715). Peripheral blood levels of VEGF were significantly higher in EM and CM patients as opposed to controls (P-value<0.001), but not different between EM and CM patients (P-value=0.859). Serum levels of PGE2 were significantly lower in EM patients compared to controls (P-value=0.011), however similar between EM and CM patients (P-value=0.086). In migraine patients, serum levels of NGF and PGE2 positively correlated with headache frequency (NGF: ρ = 0.476 and P-value<0.001; PGE2: ρ = 0.286 and P-value=0.028), while corresponding levels of BDNF and VEGF did not correlate with headache frequency (BDNF: ρ = 0.037 and P-value=0.778; VEGF: ρ= -0.025 and P-value=0.850). CONCLUSIONS: Our findings suggest that NGF, BDNF, PGE2, and VEGF may play a significant role in migraine pathogenesis and/or chronification, and therefore might bear potential value for novel targeted abortive and prophylactic migraine therapy. Further prospective cohort studies with larger sample sizes can more robustly evaluate the implications of these findings.

B vitamins and their combination could reduce migraine headaches: A randomized double-blind controlled trial.

Background: The B vitamins can potentially help prevent migraine. This study was designed to examine the effects of supplementation with thiamine (B1), pyridoxine (B6), cobalamin (B12), folic acid (B9), and a combination of these vitamins on women with episodic migraine (EM). Methods: This study was a double-blind, placebo-controlled, randomized, clinical trial conducted on 120 women with EM. The participants were divided into the 6 groups of B1 (n = 20), B6 (n = 20), B12 (n = 20), B9 (n = 20), vitamin B complex (n = 20), and placebo (n = 20). Subjects received 1 capsule daily for 12 weeks. As part of the baseline and post-intervention phases, paper-based headache diaries were used to record the number of abortive drugs consumed and the frequency of headache attacks, and the Migraine Disability Assessment Questionnaire (MIDAS) was used to assess migraine disability. Results: A 16-week study on women with EM revealed that the mean changes in the frequency of headache attacks decreased significantly in all vitamin groups in comparison with the placebo group (P < 0.001). In contrast to the placebo, there was also a significant improvement in the migraine disability score in each vitamin group (P < 0.001). The 12-week supplementation with vitamins B9, B1, B6, B12, and B complex also brought on a significant decrease in the use of abortive drugs compared to the placebo group (P = 0.032). Conclusion: The results of this study showed that B1, B6, B12, and B9, and a combination of these vitamins could be effective as an adjuvant in treatment and prophylaxis of EM. Further large trials with long-term follow-ups will be required to confirm our results.

A case-control study of Dietary Approaches to Stop Hypertension (DASH) diets, colorectal cancer and adenomas among Iranian population.

BACKGROUND AND AIMS: Colorectal cancer (CRC) is the third most common cancer, worldwide. Recently, much attention has been given to the association between Dietary Approaches to Stop Hypertension (DASH) and CRC, however, data on colorectal adenomas (CRAs) as its precursor are scarce. Thus, the purpose of this case-control study was to investigate the association of DASH score with the risk of CRC and CRA in Iranian adults. METHOD: A total of 499 participants, including 129 CRC and 130 CRA cases, along with 240 controls, were asked about their dietary intake via a validated questionnaire. The DASH score was then calculated based on a priori methods and categorized in quartiles. Multivariate logistic regression was performed to assess the association of DASH score and the risk of CRC and CRA. RESULTS: After adjusting for confounding variables, adherence to the DASH diet was associated with a reduction in the risk of CRC and CRA, respectively (OR of 4th versus 1st quartile = 0.04, 95% CI: 0.01-0.11, OR = 0.10, 95% CI: 0.04-0.22). Also, subgroup analysis based on gender showed that women and men with a higher DASH score had a significantly lower risk of CRC and CRAs. CONCLUSION: The results of this study demonstrated that adherence to a DASH dietary pattern could reduce the risk of CRC and CRA in men and women. Promoting a DASH eating plan can be helpful in reducing the risk of CRC.

The association between dietary total antioxidant capacity and NMO-IgG seropositivity in patients with neuromyelitis optica spectrum disorder.

OBJECTIVES: There is growing evidence highlighting the role of environmental risk factors of NMO-IgG seropositivity in patients with neuromyelitis optica spectrum disorder (NMOSD). The present study investigated the possible association between dietary total antioxidant capacity (TAC) and NMO-IgG seropositivity in NMOSD patients. METHODS: Fifty-six patients with a definite diagnosis of NMOSD were included in the study. Data on patients' age, gender, height, weight, cigarette smoking status, and alcohol consumption were collected and recorded. Body mass index (BMI) was also calculated. In addition, dietary habits of patients were evaluated using an adjusted semi-quantitative food frequency questionnaire (FFQ) that consists of 168 food items. Dietary TAC was calculated using the oxygen radical absorption capacity (ORAC) method. Enzyme-linked immunosorbent assay (ELISA) method was used to determine the NMO-IgG serum status. The association between dietary TAC and odds of NMO-IgG seropositivity was measured using the logistic regression analysis. RESULTS: The mean of dietary TAC was 8362.8 (µmolTE/1000 kcal) in seronegative patients and 6609.9 (µmolTE/1000 kcal) in seropositive patients and had a significant difference between the mentioned groups of patients (P: 0.02). An inverse association was found between dietary TAC and odds of NMO-IgG seropositivity in all three regression models. The higher dietary intake of antioxidant resulted in significant findings as follows: 92% (95% CI: 0.01-0.53), 97% (95% CI: 0.00-0.34), and 97% (95% CI: 0.00-0.32) lower odds of NMO-IgG seropositivity in the fourth quartiles of the first, the second, and the third regression model, respectively. Moreover, the inverse association between fruit intake and odds of NMO-IgG seropositivity was significant in the third quartile (OR:0.10; 95%CI: 0.01-0.97). CONCLUSION: The present study indicated a significant inverse association between dietary TAC and NMO-IgG seropositivity of NMOSD patients. As no definite treatment can be offered for NMOSD and nutrition is a modifiable factor in this regard, specification of dietary factors affecting the risk of NMOSD is of great value.

The Association Between Dietary Acid Load and Odds of Migraine: A Case-Control Survey.

INTRODUCTION: It has been shown that a high acid load in the human body can affect inflammatory factors and the nitric oxide pathway. These factors are also thought to play an important role in the initiation of migraine attacks. We have therefore explored the association between dietary acid load and odds of migraine in a case-control study. METHODS: The migraine group (n = 514, diagnosed according to the International Classification of Headache Disorders 3rd edition [ICHDIII] criteria) was recruited from a tertiary headache clinic. The controls consisted of 582 sex-matched healthy volunteers who were randomly selected from the general population. A validated 168-item semiquantitative food frequency questionnaire was used for dietary intake assessments. Estimation of the dietary acid load was performed using three different measures: potential renal acid load (PRAL) score, net endogenous acid production (NEAP) score, and protein/potassium ratio. RESULTS: Multivariable logistic regression analysis showed that, in comparison with the lowest tertile, the highest tertile of dietary acid load measures, including PRAL (odds ratio [OR] 7.208, 95% confidence intervals [CI] 3.33-15.55), and NEAP (OR 4.108, 95% CI 1.924-8.774) scores and the protein/potassium ratio (OR 4.127, 95% CI 1.933-8.814), significantly increased the odds of migraine (P value for trend ≤ 0.001). CONCLUSION: In this study, high dietary acid load was associated with higher odds of migraine. It is therefore possible that restricting dietary acid load could reduce the odds of migraine in susceptible subjects. However, due to the preliminary nature of the current evidence, caution is advised in drawing a definitive conclusion. More well-designed studies are required for a better understanding of this important issue.

The effects of vitamin D3 supplementation on TGF-ß and IL-17 serum levels in migraineurs: post hoc analysis of a randomized clinical trial.

BACKGROUND: Although the exact mechanism involved in migraine pathogenesis remained uncertain, and different researches have been developed to address the role of neuroinflammation and immune dysfunction. Therefore, considering the immune protective functions of vitamin D3, we aimed to investigate the effects of daily administration of 2000 IU D3 supplements on serum status of immune markers in migraine patients. METHODS AND MATERIALS: Eighty episodic migraineurs who randomly assigned into two equal groups to receive either vitamin D3 2000 IU/d or placebo for 12-week were enrolled in this placebo-controlled double-blind trial included. Serum concentrations of transforming growth factor-beta (TGF-ß) and interleukin (IL)-17 were evaluated at baseline and after the trial via the ELISA method. RESULTS: Applying ANCOVA adjusted for baseline levels and confounding variables, it was found that the serum level of TGF-ß was significantly higher in vitamin D group (adjusted mean:1665.50 ng/L) than the placebo group (1361.90 ng/L) after the experiment (P-value = 0.012); on the other hand, vitamin D prevented the increment in IL-17 serum level in the intervention group after the trial (adjusted mean:37.84 ng/L) comparing to the controls (adjusted mean:70.09 ng/L; P-value = 0.039). The Pearson correlation analysis revealed a significant positive correlation between changes in serum 25-hydroxy-vitamin D (25(OH)D) and TGF-ß (r = - 0.306, P-value = 0.008). In contrast, no significant correlations were noted between serum 25(OH) D and IL-17 changes throughout the study. CONCLUSION: Based on the results of this study, it was revealed that 12-week vitamin D3 supplementation (2000 IU/day) could enhance the Th17/Treg related cytokines balance in episodic migraineurs. Although these findings are promising, it is needed to be extended. TRIAL REGISTRATION: The trial is registered in the Iranian registry of clinical trials (IRCT) at 11 July 2018, with IRCT code: IRCT20151128025267N6 ( https://www.irct.ir/trial/31246 ).

Dietary total antioxidant capacity and colorectal cancer and colorectal adenomatous polyps: a case-control study.

Colorectal cancer (CRC) is the third most common and the third most deadly cancer worldwide. In Iran, CRC is the third and fifth most common cancer in females and males, respectively. Chronic oxidative stress has been implicated in the development of CRC and its precursor, colorectal adenomatous polyps (CAP). While there were a few studies that suggested a favorable role of individuals antioxidants on the CRC risk, the total antioxidant capacity (TAC) of diet has been less investigated. Consequently, the aim of this study is to investigate the association of TAC with the odds of CRC and CAP. This is a case-control study. The participants were 130 cases with incident, histologically confirmed CRC, 134 cases with incident of CAP and 243 hospital-based controls. TAC has been assessed with dietary ferric-reducing antioxidant potential and oxygen radical absorbance capacity method based on collected dietary intake data through a reproducible and valid food frequency questionnaire. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association between the TAC and CRC and CAP odds were estimated by multiple logistic regression. After controlling for potential confounders, TAC was significantly associated with CRC and CAP odds. (ORQ3-Q1 for CRC = 0.25, 95% CI: 0.13-0.46, Ptrend = 0.001. ORQ3-Q1 for CAP = 0.48, 95% CI: 0.27-0.85, Ptrend = 0.01). The findings of this study suggested an inverse association between TAC and CRC and CAP risk.

Dietary nutrient patterns and the risk of colorectal cancer and colorectal adenomas: a case-control study.

Although the association between food patterns and the risk of colorectal cancer (CRC) and colorectal adenomas (CRA) has been explored previously, a distinct paucity of studies has evaluated the association of nutrient pattern and the risk of CRC and CRA as precursors of CRC. Thus, the purpose of this case-control study was to investigate nutrient patterns and their relationship with CRC and CRA in Iran. Two hundred forty hospital control, 129 newly diagnosed CRC and 130 newly diagnosed CRA patients were asked about their dietary intakes using validated questionnaires. To define the major nutrient patterns, principal component analysis was applied based on preselected nutrients, and four explainable nutrient patterns were obtained: Factor 1 (mixed), factor 2 (the antioxidant), factor 3 (dairy) and factor 4 (the high fat). Logistic regression was used to determine odds ratios (OR) with 95% confidence interval (CI) of CRC and CRA according to categories of nutrient patterns. After adjusting for confounders, factor 2 was significantly associated with lower risk for the CRC and CRA in the second category compared with the first, respectively (OR = 0.20, 95% CI: 0.12-0.34, OR = 0.34, 95% CI: 0.21-0.56). Participants in the highest category of factor 4 showed an increase in the risk of CRC and CRA, respectively, than those in the low category, in both crude and multivariate analysis (OR = 1.77, 95% CI: 1.57-2.95, OR = 1.85, 95% CI: 1.13-3.02). Among derived nutrient patterns, 'the antioxidant pattern' was inversely associated with CRC/CRA, whilst 'high fat pattern' showed a direct association with these diseases.

Diet-dependent acid load and the risk of colorectal cancer and adenoma: a case-control study.

OBJECTIVES: Colorectal cancer (CRC) is the third and second most prevalent cancer in men and women, respectively. Various epidemiological studies indicated that dietary factors are implicated in the aetiology of CRC and its precursor, colorectal adenomas (CRA). Recently, much attention has been given to the role of acid-base balance in the development of chronic diseases including cancers. Therefore, the aim of the current study is to examine the association of diet-dependent acid load and the risk of CRC and CRA. DESIGN: In this case-control study, potential renal acid load (PRAL) was computed based on dietary intake of participants assessed via a validated FFQ. Negative PRAL values indicated a base-forming potential, while positive values of PRAL implied acid-forming potential of diet. Logistic regression was used to derive OR and 95 % CI after adjusting for confounders. SETTING: Tehran, Iran. PARTICIPANTS: A total of 499 participants aged 30-70 years were included in the study (240 hospital controls, 129 newly diagnosed CRC and 130 newly diagnosed CRA). The current study was conducted between December 2016 and September 2018. RESULTS: After adjusting for potential confounders, a higher PRAL was associated with increased odds of CRC and CRA. The highest v. the lowest tertile of PRAL for CRC and CRA was OR 4·82 (95 % CI 2·51-9·25) and OR 2·47 (95 % CI 1·38-4·42), respectively. CONCLUSIONS: The findings of the current study suggested that higher diet-dependent acid load is associated with higher risk of CRC and CRA.

Evaluation of Inflammatory State in Migraineurs: A Case-control Study.

Due to inconclusive findings of previous researches, we aimed to evaluate inflammatory state biomarkers in episodic and chronic migraineurs (EM and CM patients) compared to headache-free controls in the current study. Seventy-one migraine patients and 19 age-sex-matched controls were recruited. After obtaining demographic data and recording headache characteristics, blood samples were gathered and analyzed to evaluate the serum levels of C-reactive protein (CRP), tumor necrosis factor(TNF)-α and interleukin (IL)-6. Serum levels of IL-6, CRP and TNF-α were significantly higher among subjects with CM than the EM and controls. Further, positive correlations were noted for number of headache days/month and serum IL-6 (r=0.53, p<0.001), CRP (r=0.62, p<0.001), and TNF-α (r=0.58, p<0.001). In sum, according to current findings, a pro-inflammatory state was detected among chronic and episodic migraineurs compared to healthy control, as revealed by augmented concentrations of pro-inflammatory cytokines (e.g. IL6, CRP, and TNF-α). It was also underlined that with increasing levels of inflammatory factors, headaches tended to be more chronic. However, in order to confirm the hypothesis that neuroinflammation plays a role in migraine pain genesis, long-term cohort studies and well-designed experimental and randomized controlled trials are required.

Cinnarizine as an alternative recommendation for migraine prophylaxis: a narrative review.

INTRODUCTION: Despite the available prophylactic and acute drugs for migraine management, this disabling disorder remains undertreated especially among pediatrics. In this review, the authors aim at assessing the preventive role cinnarizine plays in treating migraine based on previously published studies. AREAS COVERED: Randomized clinical trials, randomized controlled trials, non-randomized open-label trials, and retrospective studies concerning cinnarizine in migraine prevention in children and adults were reviewed. Especial attention was given to the response rate, migraine characteristics, and tolerability. EXPERT OPINION: The majority of reviewed trials demonstrated that cinnarizine is comparable to the conventional drugs used in migraine prophylaxis. However, most of the reviewed studies were limited by a non-controlled open-label design. Due to poor planning and possibility of high placebo responses, particularly in children and adolescents, the interpretation of open-label studies' results should be done cautiously. The evidence shows that cinnarizine's effectiveness was more promising in pediatric migraineurs and adults with migraine-associated vertigo such as vestibular migraine. Therefore, while the efficacy of cinnarizine cannot be dismissed, before reaching a definite conclusion on its effectiveness, it is necessary to do further high-quality RCTs among both children and adults.

The relationship between the index of nutritional quality and the risk of colorectal cancer and adenoma : a case-control study.

OBJECTIVE: Colorectal cancer is one of the most common cancers in the world, whereas dietary factors are its most modifiable risk factors. The index of nutritional quality is considered as a general overview of the nutrient content of diet. The aim of this study is to determine the relationship between the index of nutritional quality and the risk of colorectal cancer and adenomas. METHODS: Overall, 129 colorectal cancer and 130 colorectal adenoma cases and 240 healthy controls were studied in three major general hospitals in Tehran province, Iran. Index of nutritional quality scores were calculated based on information on the usual diet that was assessed by a valid and reliable Food Frequency Questionnaire. Multivariate logistic regression was used to estimate the relationship between the index of nutritional quality scores and the risk of colorectal cancer and adenoma. RESULTS: After controlling for several confounding factors, the index of nutritional quality of calcium, vitamin C, riboflavin, folate and fiber were associated with decreased risk of colorectal cancer [ORcalcium: 0.21 (0.08-0.52), ORvitC: 0.16 (0.09-0.28), ORvitB2: 0.35 (0.18-0.65), ORfolate: 0.33 (0.16-0.65), ORfiber: 0.35 (0.21-0.58)]. Also, the inverse association were observed between risk of CRA and the index of nutritional quality of calcium, vitamin C, riboflavin, folate and fiber [OR calcium: 0.32 (0.14-0.74), ORvitC: 0.51 (0.34-0.73), ORvitB2: 0.48 (0.28-0.82), OR folate: 0.44 (0.23-0.81), OR fiber: 0.62 (0.42-0.92)]. CONCLUSION: This study showed that individuals who have a healthier diet, high in calcium, vitamin C, riboflavin, folate and fiber and food groups like fruits, vegetables and whole-grain and less in sweets and red or process meats are at a lower risk of colorectal cancer and CRA than those with unhealthy and poor diet.

The effects of vitamin D supplementation on interictal serum levels of calcitonin gene-related peptide (CGRP) in episodic migraine patients: post hoc analysis of a randomized double-blind placebo-controlled trial.

BACKGROUND: Emerging evidence showed promising effects of vitamin D on headaches characteristics. Thus, it seems there is still a need for more researches to clarify the mechanisms by which this vitamin exerts anti-migraine effects. METHODS: The present study was conducted as a 16-week randomized double-blind placebo-controlled trial on 80 episodic migraine patients allocated in 2 parallel groups each consisted of 40 patients who received vitamin D 2000 IU/d or placebo. At baseline and after the intervention completion, headache diaries and migraine disability assessment questionnaire (MIDAS) were used to assess migraine related variables in patients. Also, interictal serum concentration of calcitonin gene-related peptide (CGRP) (as the dominant mediator of migraine pain pathogenesis) was evaluated using ELISA method. RESULTS: The mean (SD) of age in the vitamin D and placebo groups was 37 (8) and 38 (12) years, respectively. ANCOVA test adjusted for baseline values, and confounders showed vitamin D supplementation resulted in a significant improvement in MIDAS score after 12 weeks in the intervention group (21.49 (16.22-26.77)) compared to placebo (31.16 (25.51-36.82) P value: 0.016). Moreover, after controlling for baseline levels, and other variables using ANCOVA, CGRP level was appeared to be significantly lower following vitamin D supplementation (153.26 (133.03-173.49) ng/L) than the patients in the placebo arm (188.35 (167.15-209.54) ng/L) (P value = 0.022). CONCLUSION: According to the current findings, vitamin D supplementation in episodic migraineurs, particularly in those with migraine with aura, may potentially improve migraine headache characteristics and disability probably through attenuating CGRP levels. Therefore, these results could provide a new insight into anti-nociceptive effects of vitamin D; however, more studies are required to confirm our findings. TRIAL REGISTRATION: The trial is registered in the Iranian registry of clinical trials (IRCT) at 11 July 2018, with IRCT code: IRCT20151128025267N6.

Vitamin D3 might improve headache characteristics and protect against inflammation in migraine: a randomized clinical trial.

INTRODUCTION: Due to anti-inflammatory effects of vitamin D3, we aimed to explore the effects of supplementation with this vitamin on headache characteristics and serum levels of pro/anti-inflammatory markers in migraineurs. METHODS AND MATERIALS: This placebo-controlled, double-blind study included 80 episodic migraineurs who randomly assigned into two equal groups to receive either daily dose of vitamin D3 2000 IU (50 µg) or placebo for 12 weeks. At baseline and after the trial, headache characteristics were determined using diaries and serum levels of interleukin (IL)-10, IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (Cox-2) were assessed via ELISA method. RESULTS: At the end of trial, analysis of covariance (ANCOVA) adjusted for baseline values, and confounders revealed that vitamin D3 supplemented group experienced significantly lower headache days per month (4.71), reduced attacks duration (12.99 h/attack), less severe headaches (5.47, visual analog scale), and lower analgesics use/month (2.85) than placebo group (6.43, 18.32, 6.38 and 4.87, respectively) (P values < 0.05). Using ANCOVA adjusted for baseline levels and confounding variables, it was found that serum levels of IL-10 and Cox-2 did not significantly differ between groups after the experiment; whereas, iNOS serum level was significantly reduced in the intervention group (106.06 U/L) comparing to the controls (156.18 U/L P : 0.001). Also, the patients receiving vitamin D3 yielded a marginally significant lower IL-6 serum concentration (76.43 ng/L) compared to placebo (93.10 ng/L) (P value:0.055). CONCLUSION: Based on the results of this study, we found that 2000 IU (50 µg)/day vitamin D3 supplementation for 12 weeks could improve headache characteristics and might reduce neuro-inflammation in episodic migraine.

Estimating quality of life in a headache referral population based on Migraine disability assessment scale and headache impact test.

Background: Headache is among the most common disabling neurologic disorders. We measured quality of life in chronic migraine (CM) and episodic migraine (EM), stratified by medication overuse headache (MOH) and presence of aura. Methods: In this observational study, conducted from January 2016 to December 2018, adult patients referred to the tertiary headache clinic of Sina Hospital in Tehran, Iran, who met International Classification of Headache Disorders, 3rd Edition-beta (ICHD-3 ß) criteria for migraine were classified to EM and CM subtyped based on presence of aura and MOH. Validated Farsi versions of Migraine Disability Assessment Scale (MIDAS) and 6-item Headache Impact Test (HIT-6) questionnaires were used. Results: A total of 2454 patients (1907 women) were enrolled from which 1261 (51.4%) patients had EM and 1193 (48.6%) had CM, while 908 subjects (37.0%) had MOH, of whom 890 (98.0%) had CM. Median scores of MIDAS and HIT-6 were significantly higher in patients with CM compared to EM sufferers. Chronic migraineurs with MOH had a significantly higher median score of MIDAS and HIT-6 compared to patients with non-MOH CM. Also, there was a moderate positive correlation between MIDAS (disability) and HIT-6 scores (impact on patients' life) and a moderate correlation between HIT-6 and pain severity. Conclusion: The results of this study confirm that CM and MOH are associated with a higher headache-related disability and impact on life compared to EM. Therefore, treatment goals in prevention of MOH and migraine transformation warrant higher quality of life in patients with migraine.