MTHFR Gene Polymorphisms and Susceptibility to Migraine Attacks

Background and Aim:Migraine consisting of migraine with aura (MA) and migraine without aura (MO) is a painful neurovascular disorder affecting approximately 16% of the general population. A combination of genetic and environmental factors is involved in the pathogenesis of migraine. The MTHFR enzyme is involved in homocysteine (Hcy) metabolism and it has been reported that 1298 A to C and 677 C to T mutations   in the MTHFR gene are associated with an increased in plasma Hcy levels. Hcy is a highly reactive amino acid and causes endothelial injury. Because a plausible theory about vascular impairment in migraine, it is considered that mutations in MTHFR gene and folate metabolism are associated with migraine.Materials and Methods:In total, 75 patients with migraine (24 with MA and 51with MO) in accordance with the IHS criteria participated in this case-control study. Control group were 128 normal matched healthy subjecys who selected from same region without history of migraine or other neurologic disorder after interviewing and examining by a physician. Mean age at entry was 36.42±9.6 and 31.64±8.9 years old in migraine and control group respectively.  MTHFR polymorphisms were investigated by PCR-RFLP.Results:Genotypic results indicated that the prevalence of the MTHFR 677TT genotype in migraine subjects was higher than control (17.3% and 3.1% respectively, P<0.001).  Interestingly the risk of migraine was 6-fold higher in subjects possessing the MTHFR 677T homozygous variant (OR=6.5; CI95%: 2.03-20.76). No significant difference in the prevalence of MTHFR A1298C genotypes was observed in migraine group when compared to controls (P>0.001).Conclusion:It seems that MTHFR C677T is a potential genetic risk factor for migraine attacks, both in MA and MO subclasses in Iranian population. C677T and A1298C joint effect could amplify the potential influence of each SNPs.

The effect of Migri-Heal® on nitric oxide production in an in vitro inflammatory model of primary microglial cells

Background: Recently, much attention has been directed towards considering activated microgelial cells as putative targets for treatment of neurological disorders. MigriHeal® as a novel herbal remedy was introduced for the treatment of migraine headaches. The previous researches has shown that MigriHeal® extracts can decrease NO in an in vitro inflammatory model. The aim of this study was to investigate the effect of MigriHeal® on NO generation from LPS- stimulated microglia cells.Materials and Methods: Neonatal rat primary microglial cells were isolated from the mixed glial cultures and the purity of the cultures was determined by immunocytochemistry. Microglial cells were pretreated with Migri-Heal® and activated by 1μg/ml LPS. Subsequently, NO levels in the culture supernatants were measured by a griess reaction. Our results showed that Migri-Heal® 50μg/ml significantly reduced NO level in inflamed microglia in a dose-dependent manner. Results: The results showed that different concentrations of Migri-Heal® had no prominent effect on cell viability in presence of LPS as compared with the control group. In addition, the pretreatment of microglia cells with Migri-Heal® can prevent from a morphological changes of the cells into the round and phagocytic shape. Conclusion: Our study demonstrated that MigriHeal® might have NO scavenging properties. Integrative studies are warranted to uncover the novel pharmacological insights of this herbal remedy as an putative therapeutic approach against diseases - associated with inflammation

The Projection of Burden of Disease in Islamic Republic of Iran to 2025

Objective: Iran as a developing country is in the transition phase, which might have a big impact on the Burden of Disease and Injury (BOD). This study aims to estimate Burden of Disease and Injury (BOD) in Iran up to 2025 due to four broad cause groups using Disability-Adjusted Life Year (DALY). Methods: The impacts of demographic and epidemiological changes on BOD (DemBOD and EpiBOD) were assessed separately. We estimated DemBOD in nine scenarios, using different projections for life expectancy and total fertility rate. EpiBOD was modeled in two scenarios as a proportion of DemBOD, based on the extracted parameters from an international study. Findings: The BOD is projected to increase from 14.3 million in 2003 to 19.4 million in 2025 (95% uncertainty interval: 16.8, 21.9), which shows an overall increase of 35.3%. Non-communicable diseases (12.7 million DALY, 66.0%), injuries (4.6 million DALY, 24.0%), and communicable diseases, except HIV/AIDS (1.8 million DALY, 9%) will be the leading causes of losing healthy life. Under the most likely scenario, the maximum increase in disease burden due to DemBOD is projected to be observed in HIV/AIDS and Non-communicable diseases (63.9 and 62.4%, respectively) and due to EpiBOD in HIV/AIDS (319.5%). Conclusion: It seems that in the following decades, BOD will have a sharp increase in Iran, mainly due to DemBOD. It seems that communicable diseases (except HIV/AIDS) will have less contribution, and especially non-communicable diseases will play a more significant role

Long-term full-scale intelligent quotient outcomes following pediatric and childhood epilepsy surgery: A systematic review and meta-analysis

OBJECTIVE: Cognitive measures are an important primary outcome of pediatric, adolescents, and childhood epilepsy surgery. The purpose of this systematic review and meta-analysis is to assess whether there are long-term alterations (≥ 5 years) in the Full-Scale Intelligence Quotient (FSIQ) of pediatric patients undergoing epilepsy surgery. METHODS: Electronic databases (EMBASE, MEDLINE, and Scopus) were searched for English articles from inception to October 2022 that examined intelligence outcomes in pediatric epilepsy surgery patients. Inclusion criteria were defined as the patient sample size of ≥ 5, average follow- up of ≥5 years, and surgeries performed on individuals ≤ 18 years old at the time of surgery. Exclusion criteria consisted of palliative surgery, animal studies, and studies not reporting surgical or FSIQ outcomes. Publication bias was assessed using a funnel plot and the Quality in Prognosis Studies (QUIPS) toolset was used for quality appraisal of the selected articles. A random-effects network meta-analysis was performed to compare FSIQ between surgical patients at baseline and follow-up and Mean Difference (MD) was used to calculate the effect size of each study. Point estimates for effects and 95% confidence intervals for moderation analysis were performed on variables putatively associated with the effect size. RESULTS: 21,408 studies were screened for abstract and title. Of these, 797 fit our inclusion and exclusion criteria and proceeded to full-text screening. Overall, seven studies met our requirements and were selected. Quantitative analysis was performed on these studies (N = 330). The mean long-term difference between pre- and post- operative FSIQ scores across all studies was noted at 3.36 [95% CI: (0.14, 6.57), p = 0.04, I2 = 0%] and heterogeneity was low. CONCLUSION: To our knowledge, this is the first meta-analysis to measure the long-term impacts of FSIQ in pediatric and adolescent epilepsy patients. Our overall results in this meta-analysis indicate that while most studies do not show long-term FSIQ deterioration in pediatric patients who underwent epilepsy surgery, there was an increase of 3.36 FSIQ points, however, the observed changes were not clinically significant. Moreover, at the individual patient level analysis, while most children did not show long-term FSIQ deterioration, few had significant decline. These findings indicate the importance of surgery as a viable option for pediatric patients with medically refractory epilepsy

Bi-allelic variants in OGDHL cause a neurodevelopmental spectrum disease featuring epilepsy, hearing loss, visual impairment, and ataxia

The 2-oxoglutarate dehydrogenase-like (OGDHL) protein is a rate-limiting enzyme in the Krebs cycle that plays a pivotal role in mitochondrial metabolism. OGDHL expression is restricted mainly to the brain in humans. Here, we report nine individuals from eight unrelated families carrying bi-allelic variants in OGDHL with a range of neurological and neurodevelopmental phenotypes including epilepsy, hearing loss, visual impairment, gait ataxia, microcephaly, and hypoplastic corpus callosum. The variants include three homozygous missense variants (p.Pro852Ala, p.Arg244Trp, and p.Arg299Gly), three compound heterozygous single-nucleotide variants (p.Arg673Gln/p.Val488Val, p.Phe734Ser/p.Ala327Val, and p.Trp220Cys/p.Asp491Val), one homozygous frameshift variant (p.Cys553Leufs∗16), and one homozygous stop-gain variant (p.Arg440Ter). To support the pathogenicity of the variants, we developed a novel CRISPR-Cas9-mediated tissue-specific knockout with cDNA rescue system for dOgdh, the Drosophila ortholog of human OGDHL. Pan-neuronal knockout of dOgdh led to developmental lethality as well as defects in Krebs cycle metabolism, which was fully rescued by expression of wild-type dOgdh. Studies using the Drosophila system indicate that p.Arg673Gln, p.Phe734Ser, and p.Arg299Gly are severe loss-of-function alleles, leading to developmental lethality, whereas p.Pro852Ala, p.Ala327Val, p.Trp220Cys, p.Asp491Val, and p.Arg244Trp are hypomorphic alleles, causing behavioral defects. Transcript analysis from fibroblasts obtained from the individual carrying the synonymous variant (c.1464T>C [p.Val488Val]) in family 2 showed that the synonymous variant affects splicing of exon 11 in OGDHL. Human neuronal cells with OGDHL knockout exhibited defects in mitochondrial respiration, indicating the essential role of OGDHL in mitochondrial metabolism in humans. Together, our data establish that the bi-allelic variants in OGDHL are pathogenic, leading to a Mendelian neurodevelopmental disease in humans

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.

The Global Burden of Diseases, Injuries and Risk Factors 2017 includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. METHODS: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data.; We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1-4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0-8·4) while the total sum of global YLDs increased from 562 million (421-723) to 853 million (642-1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6-9·2) for males and 6·5% (5·4-7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782-3252] per 100 000 in males vs s1400 [1279-1524] per 100 000 in females), transport injuries (3322 [3082-3583] vs 2336 [2154-2535]), and self-harm and interpersonal violence (3265 [2943-3630] vs 5643 [5057-6302]). Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury

A Mathematical modeling and optimization of solar chimney power plant by SA and PSO algorithm

In this paper, a mathematical model for balancing energy and power generation in a solar chimney power plant has been developed. Using this mathematical model, the amount of power produced by a solar chimney power plant, have been investigated. The governing equations written power plants, Then Equations, using simulated annealing algorithm and particle swarm optimization were solved. To validate the model, the data contained in the reference paper is used. The results of this study show, The thermal efficiency of the solar chimney power plant, a small number. Proportion Power produced to the total energy for the reference data, approximately 0.6 percent. Most heat transfer occurs between the ground and the roof of the plant. By changing the geometry of power plant, Power, significant changes. According to energy balance, heat input is more increased temperature surfaces, As a result, waste of energy. In this method, using optimization algorithms, Speed solution Increases. And by increasing the number of Iteration the algorithm, Accuracy of the results will improve