Role of sarcopenia risk in predicting COVID-19 severity and length of hospital stay in older adults: a prospective cohort study.

Sarcopenia is more common in the elderly and causes adverse outcomes with increased morbidity and mortality. This prospective cohort study assessed the association of sarcopenia risk with the severity of COVID-19 at the time of admission and during hospitalisation and the length of hospital stay. Two hundred patients (aged ≥ 60 years) who were hospitalised for COVID-19 were enrolled using consecutive sampling between 29 December 2020 and 20 May 2021. The sarcopenia score of the patients was assessed using the Strength, Assistance in walking, Rising from a chair, Climbing stairs, and Falls questionnaire. The severity of COVID-19 was determined using the modified National Early Warning Score (m-NEWS) system for 2019 n-CoV-infected patients at admission (T1), day three (T2) and at discharge (T3). Data were analysed using SPSS, version 22 and STATA, version 14. Of the 165 patients included, thirty four (20·6 %) were at risk of sarcopenia. The length of hospital stay was slightly longer in patients with sarcopenia risk, but the difference was not significant (P = 0·600). The adjusted OR of respiratory rate (RR) > 20 /min at T1 for the sarcopenia risk group was 6·7-times higher than that for the non-sarcopenic group (P = 0·002). According to generalised estimating equations, after adjusting for confounding factors, the m-NEWS score was 5·6 units higher in patients at risk of sarcopenia (P < 0·001). Sarcopenia risk could exacerbate COVID-19 severity and increase RR at admission, as well as the need for oxygen therapy at discharge.

Fruits and vegetables intake may be associated with a reduced odds of multiple sclerosis: a systematic review and dose-response meta-analysis of observational studies.

INTRODUCTION: Multiple sclerosis (MS) is an immune-mediated condition of the central nervous system (CNS). Intake of fruits and vegetables high in vitamins, minerals, fiber, and active molecules contributes to the body's overall health, immunity, and physiological function. This study sought to review the literature and investigate the relationship between fruits and vegetables consumption and MS odds. METHODS: In the current systematic review and meta-analysis, a systematic search of original databases from inception to 21 Dec 2022 was conducted based on the PRISMA 2020 statement. Human observational studies examining the association between fruits or vegetables consumption and MS prevalence were included if they reported and provided effect size with 95% confidence intervals (CIs). RESULTS: The systematic review and meta-analysis included eight studies. Random effect model showed the protective effect of fruits (I2 = 81.0%, P for heterogeneity < 0.001; pooled OR = 0.52, 95%CI = 0.27, 0.97, P-value = 0.042) and vegetables consumption (I2 = 73.5%, P for heterogeneity = 0.002; pooled OR = 0.61, 95%CI = 0.38, 1.00, P-value = 0.050) on MS odds. According to a linear dose-response meta-analysis of four case-control studies, an increase of 100 grams of fruits per day reduced the odds of MS by 9% (I2 = 0.0%, P for heterogeneity = 0.77; pooled OR = 0.91, 95%CI = 0.83, 0.99, P-value = 0.021). CONCLUSION: Consumption of fruits and vegetables may be associated with a potential protective effect against MS. However, further confirmation is required through prospective longitudinal studies and randomized clinical trials.

Review on Headache Related to Dietary Supplements.

PURPOSE OF REVIEW: The lifetime prevalence of headaches is 96%. Approximately 11% of the adult population worldwide has a migraine headache. Migraine is a complex disorder that is more than a simple headache. So far, many underlying mechanisms, i.e. inflammatory, vascular, neurogenic have been hypothesized. In recent years evidences proposed that an energy deficit due to changes in mitochondrial function contributes to migraine pathophysiology as an upstream disorder. Recent insights suggested that the coexistence of sensory-stimuli surplus and energy-reserve shortage activate the trigeminovascular system. Some nutrients are considered as essential elements in mitochondrial bioenergetics and some others are known as natural immuno-modulatory components. Also, evidence showed their beneficial effect in headache prophylaxis and treatment. In present study, we aimed to review the available data in this field. RECENT FINDINGS: Vitamin B group, magnesium, and Coenzyme Q10 (CoQ10) are well-known for their function in mitochondrial energy metabolism. On the other hand, studies support their beneficial role in controlling migraine headache symptoms. For instance, daily intake of 400-milligram riboflavin for 3 months resulted in more than 50% reduction in migraine attacks in more than half of the consumers. According to recent evidence, vitamin D and Omega-3 which are considered as famous immune-modulatory compounds are also reported to be effective in migraine prophylaxis. For example, every 22% reduction in migraine headache occurrence was reported for every 5 ng/ml rise in serum vitamin D. Supplementation with vitamin B group, CoQ10, magnesium, vitamin D and Omega-3 could be considered as an effective, less costly strategy in headache/migraine prophylaxis.

The correlation between serum selenium, zinc, and COVID-19 severity: an observational study.

BACKGROUND: Without an adequate immune response, SARS-CoV2 virus can simply spread throughout the body of the host. Two of the well-known immunonutrients are selenium (Se) and zinc (Zn). Se and Zn deficiency might lead to inflammation, oxidative stress, and viral entry into the cells by decreasing ACE-2 expression; three factors that are proposed to be involved in COVID-19 pathogenesis. Thus, in the current study we aimed at evaluating the correlation between serum Se and Zn status and COVID-19 severity. METHODS: Eighty-four COVID-19 patients were enrolled in this observational study. Patients were diagnosed based on an infectious disease specialist diagnosis, using WHO interim guidance and the recommendations of the Iranian National Committee of Covid-19. The patients with acute respiratory tract infection symptoms were checked for compatibility of chest computed tomography (CT) scan results with that of Covid-19 and Real-time polymerase chain reaction (RT-PCR) for corona virus infection. The severity of Covid-19 was categorized into three groups (mild, moderate, and severe) using CDC criteria. Serum Zn and Se level of all subjects was measured. The severity of the disease was determined only once at the onset of disease. RESULTS: According to the results of linear regression test, there was a significant association between Zn and Se level and COVID-19 severity (ß = - 0.28, P-value = 0.01 for Se; ß = - 0.26, P-value = 0.02). However the significance disappeared after adjusting for confounding factors. Spearman correlation analysis showed a significant negative association between serum Zn, Se and CRP level (r = - 0.35, P-value = 0.001 for Se; r = - 0.41, P-value < 0.001 for Zn). CONCLUSION: Results suggest that increasing levels of Se and Zn were accompanied by a decrease in serum CRP level. However, the significant association between Se, Zn, and disease severity was lost after adjusting for confounding factors.

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.

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.

An investigation of oxidant/antioxidant balance in patients with migraine: a case-control study.

BACKGROUND: In recent years, the role of neuroinflammation and oxidative stress in migraine pathogenesis has achieved considerable interest; however, to date findings are equivocal. Thus, the objective of this study was to investigate biomarkers of oxidative stress in episodic and chronic migraineurs (EM and CM patients) and controls. METHODS: Forty-four patients with EM, 27 individuals with CM and 19 age-sex-matched controls were enrolled. After collecting data on demographic and headache characteristics, blood samples were collected and analyzed to detect serum levels of oxidative stress biomarkers (malondialdehyde (MDA) and nitric oxide (NO)); total antioxidant capacity using Trolox equivalent antioxidant capacity (TEAC) assay; and antioxidant enzymes (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase-1 (GPx-1)). RESULTS: Serum levels of CAT and SOD were significantly lower in the CM group than the EM group and controls. However, serum GPx-1 levels of the CM patients were slightly higher than the EM patients and controls (P-value≤0.001). CM patients had lower mean TEAC values than EM patients and controls. In addition, serum levels of NO and MDA were significantly elevated among subjects with CM compared to EM and control individuals (P-value≤0.001). Pearson correlation analysis revealed negative correlations between the number of days of having headaches per month and serum concentrations of the two antioxidant enzymes CAT (r = - 0.60, P-value< 0.001) and SOD (r = - 0.50, P-value< 0.001) as well as TEAC values (r = - 0.61, P-value< 0.001); however, there were positive correlations between headache days and serum GPx-1 levels (r = 0.46, P-value< 0.001), NO (r = 0.62, P-value< 0.001), and MDA (r = 0.64, P-value< 0.001). CONCLUSION: Present findings highlighted that chronic migraineurs had lower total non-enzymatic antioxidant capacity and higher oxidative stress than episodic migraineurs and control individuals. Although more studies are needed to confirm these data, applying novel prophylactic medications or dietary supplements with antioxidant properties could be promising in migraine therapy.

Serum Vitamin B12 and Methylmalonic Acid Status in Migraineurs: A Case-Control Study.

BACKGROUND: Although the exact pathophysiological mechanistic pathways that result in the initiation of migraine attacks remain unclear, there are some proposed mechanisms including neurogenic inflammation, trigeminovascular system activation, vascular dysfunction, and augmented release of nitric oxide (NO) and homocysteine (Hcy). Vitamin B12 is thought to be involved in important pathways that seem to be related to the pathogenesis of migraine including scavenging against NO and prevention of hyperhomocysteinemia. Therefore, the aim of the current study was to evaluate the serum vitamin B12 and methylmalonic acid (MMA) status in a group of migraine patients compared to healthy controls. METHODS: After the recruitment of cases and controls, demographic data and migraine characteristics (including the number of headache days, severity of headaches, and duration of each attack in hours) were recorded. Serum vitamin B12 and MMA levels were measured using the enzyme-linked immunosorbent assay technique. RESULTS: Seventy migraine patients and 70 healthy subjects were enrolled in this case control study. The serum levels of B12 were found to be significantly lower in migraine patients than in healthy subjects (512 ± 300 vs 667 ± 351 pg/mL, P = .007); whereas migraineurs had higher levels of MMA than controls (1.39 [0.59,4.01] vs 1.01 [0.49,1.45] µg/dL, P = .027). In the fully adjusted multiple regression model, those in the highest vs the lowest serum B12 quartile had 80% decrease in the odds of having migraine ([OR = 0.20, 95% CI = 0.05-0.73], [P for trend = .008]); while, patients in the highest quartile of MMA had more than 5 times increased risk of having migraine ([OR = 5.44, 95% CI = 1.49-19.87] [P for trend = .002]). There was no association between serum B12 and MMA levels and headache characteristics. CONCLUSION: Taken together, these findings suggest that participants with lower vitamin B12 and higher MMA levels that considered as lower functional activity of B12 had higher odds of migraine.

Vitamin D in migraine headache: a comprehensive review on literature.

INTRODUCTION: As a primary headache, migraine has been established as the first leading disability cause worldwide in the subjects who aged less than 50 years. A variety of dietary supplements have been introduced for migraine complementary treatment. As an anti-inflammatory and antioxidant agent, vitamin D is one of these agents which has been of interest in recent years. Although higher prevalence of vitamin D deficiency/insufficiency has been highlighted among migraineurs compared to controls, there is not any consensus in prescribing vitamin D in clinical practice. Therefore, in the current review, in addition to observational and case-control studies, we also included clinical trials concerning the effects of vitamin D supplementation on migraine/headache. METHODS: Based on a PubMed/MEDLINE and ScienceDirect database search, this review study includes published articles up to June 2019 concerning the association between migraine/headache and vitamin D status or supplementation. RESULTS: The percentage of subjects with vitamin D deficiency and insufficiency among migraineurs and headache patients has been reported to vary between 45 and 100%. In a number of studies, vitamin D level was negatively correlated with frequency of headaches. The present findings show that supplementation with this vitamin in a dose of 1000-4000 IU/d could reduce the frequency of attacks in migraineurs. CONCLUSION: It seems a high proportion of migraine patients might suffer from vitamin D deficiency/insufficiency. Further, the current evidence shows that in addition to routine drug therapy, vitamin D administration might reduce the frequency of attacks in migraineurs. However, these results have yet to be confirmed.

The association between dietary tryptophan intake and migraine.

Migraineurs have been identified to have chronically decreased serotonin levels while its concentrations markedly increase during ictal periods. Regarding the importance of adequate tryptophan intake in regulating serotonin homeostasis and subsequent effect on migraine attacks, we designed the current study. The migraine group (n = 514, diagnosed according to the ICHDIII criteria) was recruited from a tertiary headache clinic. The controls consisted of 582 sex-matched healthy volunteers who were randomly selected from general population. After collecting demographic and anthropometric data, a validated 168-item semi-quantitative food frequency questionnaire (FFQ) was used for dietary intake assessments. Multiple regression models were applied to explore the relationship between migraine and tryptophan intake. The mean (SD) of the age of participants in the controls and migraine group was 44.85 (13.84) and 36.20 (9.78) years, respectively. The multiple regression models were adjusted for age (year), sex, body mass index (BMI) (kg/m2), total daily energy intake (kcal/day), dietary intakes of total carbohydrates (g/day), animal-based protein (g/day), plant-based protein (g/day), total fat (g/day), saturated fat (g/day), and cholesterol (mg/day). It was shown that there is a negative association between tryptophan intake and migraine risk ((OR in the 3rd quartile = 0.46; 95% CI = 0.25-0.85) (OR in the 4th quartile = 0.40; 95% CI = 0.16-0.98) compared with the first quartile; P for trend = 0.045). Therefore, our results showed that subjects who had a median intake of 0.84-1.06 g of tryptophan per day had reduced odds of developing migraine by approximately 54-60%, relative to those consumed ≤ 0.56 g/day.

Association of diet and headache.

The global prevalence of migraine as a primary headache has been estimated as 14.4% in both sexes. Migraine headache has been ranked as the highest contributor to disability in under 50 years old population in the world. Extensive research has been conducted in order to clarify the pathological mechanisms of migraine. Although uncertainties remains, it has been indicated that vascular dysfunction, cortical spreading depression (CSD), activation of the trigeminovascular pathway, pro-inflammatory and oxidative state may play a putative role in migraine pain generation. Knowledge about pathophysiological mechanisms of migraine should be integrated into a multimodal treatment approach to increase quality of life in patients. With respect to this, within the integrative health studies growing interest pertains to dietary interventions. Although the number of studies concerning effects of diet on headache/migraine is not yet very large, the current article will review the available evidence in this area. All publications on headache/migraine and dietary interventions up to May 2019 were included in the present review through a PubMed/MEDLINE and ScienceDirect database search. According to the current findings, Ketogenic diet and modified Atkins diet are thought to play a role in neuroprotection, improving mitochondrial function and energy metabolism, compensating serotoninergic dysfunction, decreasing calcitonin gene-related peptide (CGRP) level and suppressing neuro-inflammation. It can also be speculated that prescription of low glycemic diet may be promising in headache/migraine control through attenuating the inflammatory state. Moreover, obesity and headaches including migraine could be attributed to each other through mechanisms like inflammation, and irregular hypothalamic function. Thereby, applying dietary strategies for weight loss may also ameliorate headache/migraine. Another important dietary intervention that might be effective in headache/migraine improvement is related to balance between the intake of essential fatty acids, omega-6 and omega-3 which also affect inflammatory responses, platelet function and regulation of vascular tone. Regarding elimination diets, it appears that targeted these diets in migraine patients with food sensitivities could be effective in headache/migraine prevention. Taken together, dietary approaches that could be considered as effective strategies in headache/migraine prophylaxis include weight loss diets in obese headache patients, ketogenic and low-calorie diets, reducing omega-6 and increasing omega-3 fatty acid intakes.

Enhancement of therapeutic DNA vaccine potency by melatonin through inhibiting VEGF expression and induction of antitumor immunity mediated by CD8+ T cells.

To be effective, therapeutic cancer vaccines should stimulate both an effective cell-mediated and a robust cytotoxic CD8+ T-cell response against human papillomavirus (HPV)-infected cells to treat the pre-existing tumors and prevent potential future tumors. In this study, the therapeutic experiments were designed in order to evaluate antitumor effect against the syngeneic TC-1 tumor model. The anti-tumor efficacy of a HPV-16 E7 DNA vaccine adjuvanted with melatonin (MLT) was evaluated in a C57BL/6 mouse tumor model by measuring tumor growth post vaccination and the survival rate of tumor-bearing mice, analyzing the specific lymphocyte proliferation responses in control and vaccinated mice by MTT assay. The E7-specific cytotoxic T cells (CTL) were analyzed by lymphocyte proliferation and lactate dehydrogenates (LDH) release assays. IFN-γ, IL-4 and TNF-α secretion in splenocyte cultures as well as vascular endothelial growth factor (VEGF) and IL-10 in the tumor microenvironment were assayed by ELISA. Our results demonstrated that subcutaneous administration of C57BL/6 mice with a DNA vaccine adjuvanted with MLT dose-dependently and significantly induced strong HPV16 E7-specific CD8+ cytotoxicity and IFN-γ and TNF-α responses capable of reducing HPV-16 E7-expressing tumor volume. A significantly higher level of E7-specific T-cell proliferation was also found in the adjuvanted vaccine group. Furthermore, tumor growth was significantly inhibited when the DNA vaccine was combined with MLT and the survival time of TC-1 tumor bearing mice was also significantly prolonged. In vivo studies further demonstrated that MLT decreased the accumulation of IL-10 and VEGF in the tumor microenvironment of vaccinated mice. These data indicate that melatonin as an adjuvant augmented the cancer vaccine efficiency against HPV-associated tumors in a dose dependent manner.

Serum Vitamin D Status in a Group of Migraine Patients Compared With Healthy Controls: A Case-Control Study.

OBJECTIVE: The association between serum vitamin D and migraine is investigated in this research.s BACKGROUND: Although the pathogenesis of migraine headache is not fully understood, the possible role of inflammation and disturbed immune system has been proposed; thus, higher levels of vitamin D might reduce the risk of migraine. However, the results of related studies have been inconclusive. METHODS: Seventy healthy individuals and 70 age- and sex-matched migraineurs (34 chronic and 36 episodic migraineurs), diagnosed according to the International Headache Society criteria (ICHD-IIIß), were recruited. After obtaining baseline data and assessing migraine disability, a 30-day headache diary was given to the participants. Blood samples were obtained and 25(OH)D serum concentrations were determined using ELISA techniques. Serum 25(OH)D under 20, 20-29, and 30-100 ng/mL were considered deficient, insufficient, and sufficient, respectively. The applied statistical tests for between-group comparisons include independent-sample t-test, chi-square, and analysis of variance. Multiple regression analysis was also performed to identify the possible risk factors of migraine headache. RESULTS: Migraine patients had significantly lower mean (SD) of serum VitD (30 (16) ng/mL) than healthy subjects (43 (19) ng/mL) (P < .001). The number (%) of subjects with VitD deficiency and insufficiency was significantly higher among the migraineurs (36 (53.7%)) than the controls (18 (26.1%)) (P < .0001). A significant negative association between migraine headache and serum VitD was detected in the fully adjusted multiple regression models when comparing the third and the highest serum 25(OH)D quartiles with the lowest (OR = 0.20; 95% CI = 0.05-0.77; OR = 0.17; 95% CI = 0.04-0.64, respectively, P for trend = .009). For each 5 ng/mL increase in serum 25(OH)D, there was a 22% odds decrease in the odds of migraine (OR = 0.78; 95% CI = 0.68-0.90; P = .001). CONCLUSION: We have found that a higher level of serum VitD (between 50 to less than 100 ng/mL) among a sample of the Iranian population is associated with 80-83% lower odds of migraine headache than those with serum 25(OH)D levels below 20 ng/mL. However, there is a need for well-designed clinical trials to investigate beneficial effects of increased serum 25(OH)D on lower risk of migraine.

The serum level of inflammatory markers in chronic and episodic migraine: a case-control study.

The exact mechanism of the migraine pathophysiology remained unclear. Although there are some reports showing low-grade inflammation in migraineurs, further studies are needed in this field. Thus, we designed a study to evaluate the serum levels of two main proinflammatory markers in migraine patients. In this case-control research, 43 migraine patients (23 chronic and 20 episodic migraineurs) and 40 age-sex-matched headache-free controls were studied. Demographic, dietary, and anthropometric data, headache characteristics, and serum C-reactive proteins (CRP) and tumor necrosis factor-alpha (TNF-α) assessments were collected. The mean ± SD age of the case and control groups were 36.98 ± 9.91 and 34.84 ± 9.75 years respectively. Compared to control subjects, both episodic and chronic migraineurs had significantly higher median levels of TNF-α (0.24, 0.95, and 1.90 pg/ml, respectively; P value < 0.001). Also, we observed a positive association between the TNF-α levels and the odds of having migraine after considering gender, age, body mass index, and dietary intakes of energy, carbohydrate, protein, fat, and mono and poly unsaturated fatty acids in the multivariable regression models (OR = 2.15; 95% CI 1.31-3.52; P value < 0.001). However, no significant association was demonstrated between migraine and serum CRP (OR = 2.91; 95% CI 0.87-9.78; P value = 0.08). These findings supported that inflammatory state could be related to the pathogenesis of migraine and it can thus be suggested that this effect might be beyond migraine progression. Further detailed studies are needed to investigate the importance of these findings in the pathogenesis of migraine headache.

Comorbidity of gastrointestinal disorders, migraine, and tension-type headache: a cross-sectional study in Iran.

Migraine can be accompanied by some gastrointestinal (GI) disorders. In this study, we aimed to investigate the relationship between migraine and tension-type headache (TTH) and different lower and upper GI disorders as well as non-alcoholic fatty liver (NAFLD) and cholelithiasis. This cross-sectional study included 1574 overweight and obese participants who were referred to the Obesity Research Center of Sina Hospital, Tehran, Iran. The diagnosis of migraine and TTH was made by an expert neurologist based on the international classification of headache disorders-III ß (ICHD III ß). GI disorders, including irritable bowel syndrome (IBS), constipation, heartburn, dyspepsia, non-alcoholic fatty liver (NAFLD), and cholelithiasis, were diagnosed by a gastroenterology specialist. The overall mean age of participants was 37.44 ± 12.62. A total of 181 (11.5%) migraine sufferers (with and without aura) and 78 (5%) TTH subjects were diagnosed. After adjusting for potential confounders by multivariable regression models, migraine had significant association with IBS (OR = 5.16, 95% CI = 2.07-12.85, P = 0.000), constipation (OR = 3.96, 95% CI = 2.25-6.99, P = 0.000), dyspepsia (OR = 4.12, 95% CI = 2.63-6.45, P = 0.000), and heartburn (OR = 5.03, 95% CI 2.45-10.33, P = 0.000), while the association between migraine and NAFLD was marginally significant (OR = 2.03, 95% CI = 0.98-4.21, P = 0.055). Furthermore, the prevalence of NAFLD (OR = 2.93, 95% CI 1.29-6.65, P = 0.010) and dyspepsia (OR = 4.06, 95% CI = 2.24-7.34, P = 0.000) was significantly higher in TTH patients than the headache-free group. These findings show an association between GI disorders and primary headaches especially migraine and are, therefore, of value to the management of migraine and TTH. Further studies should investigate the etiology of the relationship between all subtypes of primary headaches and GI disorders.

Celecoxib vs prednisone for the treatment of withdrawal headache in patients with medication overuse headache: a randomized, double-blind clinical trial.

OBJECTIVE: To compare the efficacy of celecoxib for treatment of withdrawal headache vs prednisone in patients with medication overuse headache (MOH). METHODS: In this prospective, double-blind, parallel-group clinical trial, 97 consecutive subjects with MOH were randomized (simple randomization using computer-generated numbers) for treatment with either 400 mg/day celecoxib (for the first 5 days then decreased at a rate of 100 mg every 5 days) or prednisone 75 mg/day orally (for the first 5 days then tapered off every 5 days). Subjects who met the International Headache Society criteria for MOH were included in the trial. The change in headache days and intake of rescue medication were considered as primary outcomes while the change in headache severity defined as a secondary outcome. RESULTS: Patients treated with celecoxib experienced lower headache intensity during the first 3 weeks after withdrawal (after 3 weeks, the median of visual analog scale was 3 for patients in celecoxib group vs 4.5 for prednisone group [P<.001]). However, headache frequency and the need for rescue medication intake were not different between 2 groups. CONCLUSION: During withdrawal in MOH, in order to reduce headache days or rescue medication intake, using either of celecoxib or prednisone as a bridge is not different.

Healthy eating index 2015 might be associated with migraine headaches: Results from a Case-Control study.

Migraine headaches are the most prevalent disabling primary headaches, affecting individuals at an active age. Dietary interventions are considered low-cost and practical approaches to migraine prophylaxis. Hence, the present study aimed to assess the association between adherence to the Healthy Eating Index 2015 (HEI-2015) and migraine headaches. The present case-control study was conducted on 476 newly diagnosed adults with migraine headaches, based on the International Classification of Headache Disorders 3rd edition (ICHDIII criteria(, and 512 healthy controls. Participants' dietary intakes were collected using a validated, 168-item semi-quantitative food frequency questionnaire (FFQ). The association between HEI-2015 and migraine headaches was assessed using logistic regression models. Although the trend was not statistically significant, being in the 4th quantile of the HEI-2015 was associated with about 50% lower odds of migraine headaches in both primary (adjusted for age and gender) (odds ratios (OR): 0.51, 95% confidence intervals (CI): 0.33, 0.78) and fully adjusted models (additionally adjusted for body mass index (BMI) and total calories) (adjusted OR: 0.50, 95%CI: 0.32, 0.77). Intriguingly, the odds of migraine headaches were significantly higher in those in the last quantile of "Total Fruits," which is equal to more than 237 g per 1000 kcal (aOR: 2.96, 95%CI: 1.99, 4.41) and "Whole Fruits," which is equal to more than 233 g per 1000 kcal (aOR: 2.90, 95%CI: 1.94, 4.31). Similarly, higher intakes of "Dairy," which is equal to more than 138 g per 1000 kcal (aOR: 2.66, 95%CI: 1.71, 4.14), and "Total Protein Foods," which is equal to more than 259 g per 1000 kcal (aOR: 2.41, 95%CI: 1.58, 3.70), were associated with higher odds of migraine headaches. The current study revealed an indirect association between HEI-2015 and its components, including "Greens and Beans," "Whole Grains," "Refined Grains," and "Added Sugars" and lower odds of migraine headaches.

Behavioural and histopathological assessment of the effects of periodic fasting on pentylenetetrazol-induced seizures in rats.

OBJECTIVES: Periodic fasting (PF) was suggested to display antiepileptic and neuroprotective effects, which is in stark contrast to severe fasting or starvation. However, these beneficial effects seem to depend on the type and duration of the used feeding protocol. There are discrepancies concerning both antiepileptic and neuroprotective effects of a PF-diet during repetitive seizures in different epilepsy models. This study was designed to evaluate the effects of different PF protocols on behavioural and histopathological consequences of epilepsy in adult rats. METHODS: Recurrent generalized seizures were caused by repetitive injection of pentylenetetrazol (PTZ) for a period of 4 weeks every other day. While control animals had free access to food and water, animals on a PF-diet were on intermittent fasting for 24 hours every 48 hours for 4 weeks before (T1), after (T2), or both before and after (T3) the injection of PTZ. Behavioural studies were carried out after PTZ injections and histological investigations were performed after the experiments were completed. RESULTS: Seizure assessment showed that the severity of seizures was significantly decreased in groups T1 and T3 when compared with control rats. Dark neuron densities in hippocampal CA1 and CA3 areas were decreased in PF groups, but never in the temporal cortex. The PF-diet also decreased the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling-positive neurons in the hippocampus in both areas and all PF-diet protocols. DISCUSSION: These results support the idea that a PF-diet has anticonvulsive and neuroprotective effects on epileptic rats but underlines that different PF-diet protocols can have varying effects. Anticonvulsive effects were strongest when the PF-diet started before the onset of excitotoxic injuries, the number of dark neurons was decreased and apoptosis was prevented by all PF-diet protocols investigated in this work. Further evaluation of PF-diet protocols for possible clinical anticonvulsant and neuroprotective effects is suggested.

The effect of body mass index on the morbidity and outcomes of COVID-19 in Iranian patients with multiple sclerosis.

Background: It seems that patients with multiple sclerosis (MS) are at a higher risk for coronavirus disease 2019 (COVID-19) implications due to being subjected to immunomodulatory or immunosuppressive treatments. Besides, obesity as a risk factor may lead to more adverse consequences. The relationship between obesity and COVID-19 morbidity and outcomes in Iranian patients with MS still remains unclear. Methods: A cross-sectional study was conducted in Sina Hospital, Tehran, Iran. Patients with MS were asked to complete an online questionnaire in the Google Form format. Demographic information, clinical information including MS disease-related factors, COVID-19-related factors, and anthropometric information were recorded. Totally, 492 patients filled the questionnaire during two weeks in November 2021, by the response rate of 21.6%. Body mass index (BMI) was categorized based on the standard classification of the World Health Organization (WHO). The logistic regression was used to examine the risk of morbidity and chi-square test/one-way analysis of variance (ANOVA) was employed to determine the difference regarding severity and symptoms among groups. Results: In the fully adjusted model, the odds ratio (OR) of COVID-19 morbidity in class II obese participants was significantly 5.41 times higher than that in the normal BMI group [OR: 5.41, 95% confidence interval (CI): 1.00-29.09]. COVID-19 severity was significantly different among BMI groups (P = 0.024). Respiratory symptoms (P = 0.05) as well as gastrointestinal (GI) symptoms (P < 0.01) of COVID-19 were more prevalent among class I and class II obese patients compared with overweight, normal weight, and underweight groups. Moreover, no one in the class I and class II obesity groups reported COVID-19 morbidity without any symptoms (P = 0.04). Conclusion: The results of the current study support the view that obesity could play a key role in susceptibility to COVID-19 morbidity and severity of the symptoms in patients with MS. The findings recommended that neurologists pay more attention to patients' BMI during this pandemic.

Higher Dietary Acid Load Might Be a Potent Derivative Factor for Multiple Sclerosis: The Results from a Case-Control Study.

This study aimed to investigate the association between dietary acid load (DAL) and multiple sclerosis (MS), through the potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores. In a hospital-based case-control study of 109 patients with MS and 130 healthy individuals, a validated 168-item semi-quantitative food frequency questionnaire and a logistic regression model were used to evaluate the association between the DAL and MS. After adjusting for age (years), gender (male/female), body mass index (Kg/m2), and total calories (Kcal), the MS odds were 92% lower for those in the highest tertile of total plant-based protein (OR: 0.08, 95%CI: 0.03, 0.23; p-value < 0.001) and about four times higher for those in the highest tertile of the PRAL (OR: 4.16, 95%CI: 1.94, 8.91; p-value < 0.001) and NEAP scores (OR: 3.57, 95%CI: 1.69, 7.53; p-value < 0.001), compared to those in the lowest tertile. After further adjusting for sodium, saturated fatty acid, and fiber intake, the results remained significant for total plant-based protein intake (OR: 0.07, 95%CI: 0.01, 0.38; p-value = 0.002). In conclusion, a higher NEAP or PRAL score may be associated with increased odds of MS, while a higher intake of plant-based protein instead of animal-based protein may be protective.