Role of TNF-α in the Pathogenesis of Migraine.

Background: Neurogenic neuroinflammation has a wide role in migraine pathogenesis including the transition from episodic migraine to chronic one. The seed molecule of neurogenic neuroinflammation, i.e., the TNF-α proinflammatory molecule, has gathered a lot of attention. This pleiotropic cytokine is a classical component of inflammatory soup, secreted by the microglial cell, and promotes a wide range of inflammatory reactions. Aim: In this review, we aimed to provide a culminating and comprehending glimpse into the TNF-α in association with the migraine. Method: A systematic literature survey method with a mixture of keywords was utilized to grasp the different elements that represent the association between TNF-α and migraine. Discussion. Highlighted the probable involvement of the TNF-α with migraine, the complexity of the matter such as activation of NF-KB signaling cascade, autoactivation, sensitization, and increased likelihood of transition cannot be neglected. Being TNF-α as a core node, it becomes the factor for linking diseases such as chronic inflammatory disorders, including COVID-19, and also interaction with other genes to develop severe conditions. Conclusion: To this end, TNF-α plays a critical role in chronification, and inhibiting its signaling would likely be a crucial strategy for migraine therapy.

Comprehensive analysis of genes associated with migraine in the Indian population: a meta-analysis of genetic association studies with trial sequential analysis.

Migraine is a complex disorder with multigenic inheritance and is characterized by the cardinal symptom of unilateral headache. Many genes are responsible for increasing the susceptibility of disease within different populations. Therefore, our primary aim in this review was to catalog the many genes that have been studied in India and after collecting the necessary information, we calculated a more precise risk relationship between an identified variation and migraine. The gene and its associated risk variant were discovered in the Indian population using a PRISMA-based systematic literature review guideline from online databases such as PubMed & Google Scholar. We constructed pooled odds ratios with 95% confidence intervals using multiple genetic models. Also, we looked for heterogeneity using Cochran's Q Test and the I2 statistic. Publication bias was analyzed using Begg's and Egger's tests. A p-value less than 0.05 was judged to be statistically significant for all tests. After a critical analysis, a total of 24 studies explored about 21 genes with 31 variants out of which only nine genes have been studied more than two times in the Indian population and thus were found eligible for the meta-analysis. It has been found, that the ACE-DD variant (allele model: OR: 1.37 [1.11-1.69], I2 = 0%/ fixed model), ESR1-PvuII (allele model: OR: 1.47 [1.24-1.74], I2 = 0%/ fixed model) significantly increases the risk of migraine in Indian population. Also, a protective role of the LRP1-rs11172113variant was observed for both migraine and its clinical subtype i.e., MA (allelic model: OR of 0.65 [0.50-0.83] I2 = 44% and allele: OR: 0.54 [0.37-0.78], I2 = 52%) respectively. Overall, the results of this meta-analysis indicated that the ACE-DD variant and the ESR1-PvuII were associated with an increased risk of migraine in the Indian community, while the LRP1-rs11172113 variant was associated with protection from migraine in this population.

A Comprehensive Investigation of Risk Association Between the -786 T > C, + 884 G > A, VNTR, rs743506, rs3918226 of eNOS and Susceptibility of Migraine: A Updated Meta-Analysis Utilizing Trial Sequential Analysis.

With a feature of complex pathogenic mechanisms, migraine is a well-known common neurovascular disorder. Multiple genes are responsible for hindering the susceptibility of pain threshold one of which is the eNOS gene and its variants. Multiple independent observational studies with case-control design produced conflicting findings, which can be attributed to a variety of factors including varying sample sizes, demographic stratification, technique application, etc. Therefore, in the present study we aimed to find out the precise risk between the selected variant of eNOS and the risk of migraine and its clinical subtypes using a meta-analysis approach. To find the association between the risk variants of the eNOS gene and migraine, a PRISMA-based systematic literature review strategy was utilized to search via online resources including PubMed and Google Scholar. Using several genetic models, odds ratios with 95% confidence intervals were computed to pool the data. To access heterogeneity, Cochran's Q Test and I2 statistics were utilized, while Begg's and Egger's tests were used to determine publication bias. A p-value of 0.05 or below was deemed statistically significant for all two-sided tests. The present meta-analysis was able to find out the significant protective association between rs743506 and migraine after using dominant (OR: 0.66, CI [0.49-0.86]), over-dominant (OR: 0.56, CI [0.42-0.75]), codominant model (OR: 0.58, CI[0.43-0.77]). Only significant risk association was found between rs1799983, rs3918226, and risk of migraine with aura after utilizing recessive and codominant models i.e., HR vs HW and HR vs HT. The present meta-analysis showed that rs743506 showed a protective association in comparison to rs1799983, rs3918226 which showed significant risk in the MA group. Also, TSA showed non-significant results and therefore, in conclusion, more studies are required to establish risk.

A Comprehensive Investigation into the Association Between Mthfr C677t, A1298c, and Ace I/D Variants and Risk of Migraine: an Updated Meta-Analysis of Genetic Association Studies with Trial Sequential Analysis and Meta-Regression.

Many homeostatic genes are thought to play a role in the susceptibility to migraine, making it a highly complex neurovascular disease. In this meta-analysis, our primary objective was to evaluate whether or not MTHFR variants (such as C677T and A1289C) and ACE I/D were associated with an increased risk of migraine. Using a PRISMA-based systematic literature-review guideline, internet sources such as PubMed and Google Scholar were searched to identify the genes of interest and migraine risk. To pool the data, odds ratios with 95% confidence intervals were calculated utilizing different genetic models. Cochran's Q Test and I2 statistics were used to access heterogeneity, while Begg's and Egger's tests were used to identify publication bias. All tests were two-sided, and a p-value of < 0.05 was regarded as statistically significant. The present meta-analysis observed that the C677T variant is significantly associated with the increased risk of migraine (allele model: OR:1.19, CI [1.07-1.33], I2 = 78%) and its clinical subtype i.e., MA (allele model: OR: 1.26, CI [1.09-1.45], I2 = 80%) in the overall population. Concerning the ACE- I/D, it significantly increased the risk of overall migraine and both clinical subtypes after utilizing the dominant genetic models (OR: 1.14, CI [1.01-1.29], I2% = 32). Concerning the MTHFR A1289C, only the codominant model (HR vs HT) and recessive model significantly increased the risk of overall migraine. Therefore, the findings of the present meta-analysis showed that MTHFR-C677T is an important risk factor for migraine and its clinical subtype.

Enlightening the association between TNF-α -308 G > A and migraine: a meta-analysis with meta-regression and trial sequential analysis.

BACKGROUND: Migraine is a complex neurological disorder that is characterized by a "lower threshold of neuronal hyperexcitability" with distinctive periodicity and complex vascular dysfunction. Genetic factors have impacted incredibly on the susceptibility of migraine and one such example is the TNF-α 308G > A. AIM: Therefore, we aim to provide a glimpse of the association of the TNF-α 308G > A risk on the susceptibility of migraine. METHOD: The pooled odds ratio with the associated 95% of confidence interval were calculated using different genetic models. Heterogeneity was accessed by using Cochran's Q Test and I2 statistics and Begg's and Egger's tests were used for finding the publication bias, tests were two-sided, and a p-value of < 0.05 was considered statistically significant. The Trial Sequential Analysis with Meta-regression Analysis were also utilized to find out the sample size requirement for meta-analysis to avoid type I error and source of heterogeneity respectively. RESULT: A total of 13 studies with cases: 7193 and controls: 23,091 were included and after using different genetic models, no overall association with migraine and its clinical subtype migraine with aura was observed (Allele model "OR: 1.28, 95% C.I. [0.96-1.69] and OR: 0.99,95% C.I. [0.69-1.42]) respectively. Interestingly, after sub-grouping using the "ethnicity criteria" in the migraine group, it was observed that the allelic genetic model and the dominant model were found to be significantly associated with the Asian ethnic group (OR: 1.79, 95% C.I. [1.13-2.84], and OR: 1.85, 95% C.I. [1.0927; 3.1580]. CONCLUSION: In conclusion, the present meta-analysis has provided evidence that 308G > A increases the risk of migraine only in the Asian population.

Neuroepidemiology study of headache in the region of Jammu of north Indian population: A cross-sectional study.

Background: Headache disorders now represent a major public health problem globally. It is more prevalent in developing countries with the rising trends of headache disorders observed in young adults affecting their quality of life negatively. Very little information is available on the epidemiology of headache disorders in the Jammu Division of the north Indian population. Aim: The aim of the present study was to find out the prevalence of headache and its two major types, i.e., migraine and tension-type headache (TTH), in the population of the Jammu Division. Methods: The present study was conducted in two phases: (Phase I: face-to-face interview and Phase II: E-based sampling) and the sufferers of headaches were incorporated into the study based on the International Classification of Headache Disorder-3 (ICHD-3) criteria for a representative sample. Frequency distribution and mean ± standard deviation were used in descriptive statistics to describe the data sets, while a t-test, chi-square test, multiple logistic regression, and prevalence ratio were used in inferential statistics. Results: In the present study, a total of 3,148 patients were recruited, with an overall prevalence of headache of 53.84%, with a majority of females (38.18%) over males (15.66%). As regards the type of headache, migraine was found to be of the more prevalent (33.25%) type than the TTH (20.58%). Females suffering from migraine showed the highest prevalence (25.28%), in contrast to females suffering from the TTH (12.89%). Sociodemographic variables, such as gender [female; AOR = 2.46, 95% CI (2.12-2.85), p-value < 0.0001] and marital status [married; AOR: 1.46, 95% CI (1.11-1.92) p-value = 0.006], showed a significant association with the headache. Conclusion: The present study shows that the prevalence of headache is high in the Jammu Division of Jammu and Kashmir (J&K) India, with migraine being the highly prevalent type.

Dopamine D3 receptor Ser9Gly variant is associated with impulse control disorders in Parkinson's disease patients.

INTRODUCTION: Impulse control disorders (ICD) are reported to occur at variable frequencies in different ethnic groups. Genetic vulnerability is suspected to underlie the individual risk for ICD. We investigated whether the allelic variants of dopamine (DRD3), glutamate (GRIN2B) and serotonin (HTR2A) receptors are linked to ICD in Indian Parkinson's disease (PD) patients. METHODS: We conducted a prospective, case-control study which included PD patients (70 with ICD, 100 without ICD categorized after direct psychiatric interview of patient and caregiver) and 285 healthy controls. Single nucleotide polymorphism (SNP) variants of DRD3 p.S9G (rs6280), GRIN2B c.2664C>T (rs1806201) and HTR2A c.102T>C (rs6313) were genotyped. RESULTS: Multivariate regression analysis revealed that DRD3 p.Ser9Gly (rs6280) heterozygous variant CT (OR = 2.22, 95% CI: 1.03-4.86, p = 0.041), higher daily Levodopa equivalent doses (LED) of drugs (for 100 mg LED, OR = 1.14, 95% CI: 1.01-1.29, p = 0.041), current dopamine agonist but not Levodopa use (OR = 2.16, 95% CI: 1.03-4.55, p = 0.042) and age of onset of motor symptoms under 50 years (OR 2.09, 95% CI: 1.05-4.18, p = 0.035) were independently associated with ICD. CONCLUSION: DRD3 p.Ser9Gly (rs6280) CT genotype is associated with ICD in Indian PD patients and this association is novel. Enhanced D3 receptor affinity due to gain-of-function conferred by the glycine residues could impair reward-risk assessment in the mesolimbic system and contribute to development of impulsive behaviour, in carriers of this genotype.

Surgery for "Long-term epilepsy associated tumors (LEATs)": Seizure outcome and its predictors.

OBJECTIVES: "Long-term epilepsy associated tumors (LEATs)" by definition are tumors primarily causing drug-resistant seizures for two years or more. They include low-grade glial and glioneuronal tumors with normal life expectancy. We studied a large cohort of patients with LEATs who underwent surgery through our epilepsy program. PATIENTS & METHODS: From 1998-2011, 105 patients with LEATs underwent surgery in our center. We utilized their data archived in a prospective registry to evaluate their electro-clinical-imaging characteristics affecting the long-term seizure outcome. RESULTS: Of 105 patients (age 3-50 years), mean age at surgery was 20 years and mean pre-surgical duration of epilepsy was 10.9 years. 66 (62.8%) had secondary generalized seizures. 82 had temporal tumors, 23 had extra temporal (13 frontal, 3 parietal, 2 occipital and 5 multilobar lesions) and four had associated hippocampal sclerosis. The interictal discharges and ictal onset were concordant to the lesion in 82 (78%) and 98 (93%) patients respectively. Lesionectomy and/or adjoining corticectomy or temporal lobectomy was done. Ganglioglioma was the most dominant pathological substrate in 61 (58%). During a mean follow-up of 7.5 years (range 3-16 years), 78/105 (74.2%) were seizure-free and 45 (57.4%) were totally off drugs. Secondary generalized seizures (p-0.02), temporal location of tumor (p-0.008) and spikes in third month post-operative EEG (p-0.03) caused unfavorable seizure outcome. A pre-surgical duration of epilepsy of more than 6.6 years caused less than optimal surgical outcome CONCLUSIONS: Early surgery should be considered a priority in LEATs. Presence of secondary generalized seizures is the single most important predictor of a poor seizure outcome.

Ion beam-induced shaping of Ni nanoparticles embedded in a silica matrix: from spherical to prolate shape.

Present work reports the elongation of spherical Ni nanoparticles (NPs) parallel to each other, due to bombardment with 120 MeV Au+9 ions at a fluence of 5 × 1013 ions/cm2. The Ni NPs embedded in silica matrix have been prepared by atom beam sputtering technique and subsequent annealing. The elongation of Ni NPs due to interaction with Au+9 ions as investigated by cross-sectional transmission electron microscopy (TEM) shows a strong dependence on initial Ni particle size and is explained on the basis of thermal spike model. Irradiation induces a change from single crystalline nature of spherical particles to polycrystalline nature of elongated particles. Magnetization measurements indicate that changes in coercivity (Hc) and remanence ratio (Mr/Ms) are stronger in the ion beam direction due to the preferential easy axis of elongated particles in the beam direction.

Prevalence of Cryptosporidium parvum infection in Punjab (India) and its association with diarrhea in neonatal dairy calves.

A prevalence study was contemplated to determine the prevalence of Cryptosporidium spp. in dairy farms in Punjab, India. The cryptosporidium oocysts were detected from 50 and 25.68% from 80 diarrheic and 74 non-diarrheic animals, respectively. Both shedding and intensity of shedding were significant in calves with diarrhea. The Cryptosporidium spp. appears to be common in dairy calves and an important contributor of calf diarrhea in the Punjab province. The prevalence of the infection peaked in young calves between 0 and 30 days in both the diarrheic and non-diarrheic groups (86.4 and 66.6%, respectively). The percentage distribution of positive samples, with reference to age groups of diarrheic and non-diarrheic animals was negatively correlated with increase in age. High mortality rate and case fatality rate of 35.2 and 44.4% were observed in young calves between 0 and 30 days of age.