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Background: India is a large and populous country where reliable data on headache disorders are relatively scarce. This study in northern India (Delhi and National Capital Territory Region [NCR], including surrounding districts in the States of Haryana, Uttar Pradesh and Rajasthan) continues the series of population-based studies within the Global Campaign against Headache and follows an earlier study, using the same protocol and questionnaire, in the southern State of Karnataka. Methods: This cross-sectional study used the Global Campaign's established methodology. Biologically unrelated Indian nationals aged 18–65 years were included through multistage random sampling in both urban and rural areas of NCR. Interviews at unannounced household visits followed the structured Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire in its original English version or in the validated Hindi version. Demographic enquiry was followed by a neutral headache screening question and diagnostic questions based on the International Classification of Headache Disorders edition 3 (ICHD-3), which focused on each respondent's most bothersome headache. Questions about headache yesterday (HY) enabled estimation of 1-day prevalence. A diagnostic algorithm first identified participants reporting headache on ≥ 15 days/month (H15+), diagnosing probable medication-overuse headache (pMOH) in those also reporting acute medication use on ≥ 15 days/month, and "other H15+" in those not. To all others, the algorithm applied ICHD-3 criteria in the order definite migraine, definite tension-type headache (TTH), probable migraine, probable TTH. Definite and probable diagnoses were combined. Results: Adjusted for age, gender and habitation, 1-year prevalences were 26.3% for migraine, 34.1% for TTH, 3.0% for pMOH and 4.5% for other H15+. Female preponderance was seen in all headache types except TTH: migraine 35.7% vs. 15.1% (aOR = 3.3; p < 0.001); pMOH 4.3% vs. 0.7% (aOR = 5.1; p < 0.001); other H15 + 5.9% vs. 2.3% (aOR = 2.5; p = 0.08). One-day prevalence of (any) headache was 12.0%, based on reported HY. One-day prevalence predicted from 1-year prevalence and mean recalled headache frequency over 3 months was slightly lower (10.5%). Conclusions: The prevalences of migraine and TTH in Delhi and NCR substantially exceed global means. They closely match those in the Karnataka study: migraine 25.2%, TTH 35.1%. We argue that these estimates can reasonably be extrapolated to all India. [ABSTRACT FROM AUTHOR]

Objective: To assess attention, vigilance, and executive functions in migraine patients during headache-free (interictal) periods and in healthy controls without migraine and to study the impact of migraine preventive treatment on these cognitive functions. Methods: Preventive drug-naive migraine patients, aged ≥18 years, without a history of medication overuse were studied and compared to non-migraine controls. Psychiatric comorbidity was screened by Patient Health Questionnaire-9, and those who screened positive were evaluated further by specific scales. The Epworth Sleepiness Scale assessed subjective complaints of sleep quality. Cognitive functions were assessed by Mini-Mental State Examination (MMSE), digit span forward and backward (DS-F, DS-B), trail-making tests (TMT-A and B) and Stroop word (SW), Stroop color (SC), and Stroop interference (SI) tests. Cognitive test scores at the end of 6 months following treatment were compared to baseline scores. Results: One hundred and fifty migraine patients and controls each were studied. Compared to controls, migraine patients performed significantly worse in DS-B (P < 0.0001), TMT-A (P = 0.00004), TMT-B (P < 0.0001), SW (P < 0.0001), SC (P < 0.0001), and SI (P = 0.0221). MMSE scores did not differ between patients and the controls (P = 0.3224). Compared to the patients without psychiatric comorbidity, migraine patients with psychiatric comorbidity showed no significant differences in the cognitive test scores. Significant improvement in all cognitive test scores (P < 0.001) was observed after 6 months of treatment. Conclusion: Migraine patients, compared to non-migraine controls, showed deficits in attention, vigilance, and executive functions during the interictal period, which improved with successful preventive treatment. Psychiatric comorbidities did not have a significant impact on cognitive dysfunctions. [ABSTRACT FROM AUTHOR]

Background: Knowledge of the prevalence and attributable burden of headache disorders in India is sparse, with only two recent population-based studies from South and East India. These produced conflicting results. A study in North India is needed. We report the methodology of such a study using, and validating, a Hindi translation of the Headache-Attributed Restriction, Disability, Social Handicap, and Impaired Participation (HARDSHIP) questionnaire developed by Lifting The Burden (LTB). Almost half of the Indian population speak Hindi or one of its dialects. Methods: The study adopted LTB's standardized protocol for population-based studies in a cross-sectional survey using multistage random sampling conducted in urban Delhi and a surrounding rural area. Trained interviewers visited households unannounced, randomly selected one adult member from each and applied the Hindi version of HARDSHIP in face-to-face interviews. The most bothersome headache reported by participants was classified algorithmically into headache on ≥ 15 days/month (H15 +), migraine (including definite and probable) or tension-type headache (including definite and probable). These diagnoses were mutually exclusive. All participants diagnosed with H15 + and a 10% subsample of all others were additionally assessed by headache specialists and classified as above. We estimated the sensitivity and specificity of HARDSHIP diagnoses by comparison with the specialists' diagnoses. Results: From 3,040 eligible households, 2,066 participants were interviewed. The participating proportions were 98.3% in rural areas but 52.9% in urban Delhi. In the validation subsample of 291 participants (149 rural, 142 urban), 61 did not report any headache (seven of those assessed by HARDSHIP, eight by headache specialists and 46 by both) [kappa = 0.83; 95% CI: 0.74-0.91]. In the remaining 230 participants who reported headache in the preceding year, sensitivity, specificity and kappa with (95% CI) were 0.73 (0.65-0.79), 0.80 (0.67-0.90) and 0.43 (0.34-0.58) for migraine; 0.71 (0.56-0.83), 0.80 (0.730.85) and 0.43 (0.37-0.62) for TTH and 0.75 (0.47-0.94), 0.93 (0.89-0.96) and 0.46 (0.34-0.58) for H15 + respectively. Conclusion: This study validates the Hindi version of HARDSHIP, finding its performance similar to those of other versions. It can be used to conduct population surveys in other Hindi-speaking regions of India. [ABSTRACT FROM AUTHOR]

Introduction: The available literature on vascular risk and endothelial dysfunction in patients with Chronic Migraine (CM) is limited. CM patients are known to have a higher risk of cardiovascular and cerebrovascular events. The present study aims to characterise the vascular risk and endothelial dysfunctions in CM patients and compare them with Healthy Controls (HC). Aim: To assess the vascular risk factors and biomarkers of endothelial dysfunction in CM patients and compare them with healthy non-headache controls. Materials and Methods: This cross-sectional study was conducted from October 2021 to January 2023 at the headache clinic of GB Pant Institute of Postgraduate Medical Education and Research in Delhi, India. The patients were diagnosed with CM using the International Classification of Headache Disorders-3 (ICHD-3) criteria. The patients were drug-naïve for preventive medications and did not have medication overuse headache. Clinical vascular risk factors such as Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Ankle Brachial Index (ABI), Body Mass Index (BMI), and Waist Hip Ratio (WHR) were measured. A battery of biochemical vascular risk factors, including serum C-reactive protein, leptin, insulin, fasting and post-prandial glucose, Glycosylated Haemoglobin (HbA1c), lipid profile, lipoprotein-A, pro-Brain Natriuretic Peptide (pro-BNP), and serum biomarkers of endothelial dysfunction like Intercellular Adhesion Molecules-1 (ICAM-1), Myeloperoxidase (MPO), Interleukin-6 (IL-6), Tumour Necrosis Factor-Alpha (TNFalpha), Asymmetric Dimethyl Arginine (ADMA), fibrinogen, and von Willebrand's factor were measured in all patients during the interictal period. Statistical analysis was done using the Statistical Package for Social Sciences (SPSS) version 25.0, and the Mann-Whitney U test, student's t-test, and Chi-square tests were applied. Results: Thirty-two patients with CM and thirty-two non-headache healthy subjects were included in the study (age 30.6±8.8 years; 29 females and 3 males) vs. (31.7±7.9 years; 19 females and 13 males, respectively). Compared to HC, CM patients had significantly higher DBP (81.0±8.0 mmHg vs. 66.2±6.2 mmHg; p<0.001). Among the biochemical parameters, CM patients had higher post-prandial blood sugar (mg/dL) (140.2±10.7 vs. 136.6±7.0; p=0.021), HbA1c (%) (5.8±0.8 vs. 5.6±0.4; p=0.034), serum cholesterol (mg/dL) (146.9±36.2 vs. 131±20.8), and Triglyceride (TG) levels (mg/dL) (93.2±10.8 vs. 88.5±13.0; p=0.001) compared to HCs. Among the biomarkers of endothelial dysfunction studied, levels of ICAM-1 (pg/mL) (4.5±3.8 vs. 1.3±0.62; p<0.001), MPO (pg/mL) (415.4±266.0 vs. 108.9±141.4; p=0.001), IL-6 (pg/mL) (10.8±4.9 vs. 4.2±1.5; p<0.001), and ADMA (ng/mL) (32.6±28.3 vs. 23.5±22.1; p=0.008) were higher in the CM group compared to non-headache controls. Conclusion: This study found that patients with CM have significantly higher vascular risk and evidence of endothelial dysfunction compared to healthy non-headache controls. The significantly elevated biomarkers of endothelial dysfunction may possibly be related to persistent neurogenic inflammation in CM and require further exploration through larger studies. [ABSTRACT FROM AUTHOR]

Background: The phase 3 randomized PERSIST study demonstrated the efficacy and tolerability of galcanezumab, a humanized anti-calcitonin gene-related peptide (CGRP) monoclonal antibody for prevention of episodic migraines. We present findings from the open-label extension (OLE) of PERSIST, which evaluated the long-term efficacy and safety of galcanezumab in patients from China, India, and Russia. Methods: Patients completing the 3-month double-blind period of PERSIST were eligible for the 3-month OLE. Patients previously randomized to galcanezumab (GMB/GMB group) continued to receive galcanezumab 120 mg at all three visits during the OLE whereas patients randomized to placebo received a 240 mg loading dose of galcanezumab and then two 120 mg doses (PBO/GMB group). The primary outcome was the mean change (from double-blind baseline) in the number of monthly migraine headache days (MHDs) to month 6. Other endpoints included percent reduction in monthly MHDs from double-blind baseline to month 6, functional outcomes, safety and tolerability. Results: Overall, 99% of patients completing the double-blind period entered the OLE, and 96% completed through month 6. Patients in the GMB/GMB group achieved continued improvements in efficacy, with the reduction from baseline in the mean number of monthly MHDs, and slightly increasing from 4.01 days at the end of the double-blind period to 4.62 at the end of the OLE. Of patients who were ≥ 50% responders to galcanezumab at month 3, 66% maintained this response through to month 6. Patients in the PBO/GMB group experienced a rapid reduction in the number of monthly MHDs after initiation of galcanezumab, with a mean reduction from baseline of 4.56 days by month 6. The long-term benefits of galcanezumab were also supported by improvements in other efficacy and functional endpoints. All safety findings were consistent with the known long-term safety profile of galcanezumab; no patients experienced a treatment-related serious adverse event. Conclusions: Galcanezumab was efficacious and well-tolerated in patients with episodic migraine from China, India and Russia, for up to 6 months. Trial registration: ClinicalTrisABSTRACT_pals.gov NCT03963232, registered May 24, 2019. [ABSTRACT FROM AUTHOR]

Anti N-meihyl D-aspartate receptor encephalitis (NMDAR-E) though rare, is currently considered as the commonest antibody mediated encephalitis in the world. No review on perspectives of NMDAR-E from India is available. The aim of the study was to review all the cases of NMDAR-E reported from India until June 2021 in terms of clinical features, diagnosis, and treatment, and perform a comparison of adult and paediatric cases. A literature review of NMDAR-E case reports/case series published from India till June 2021 was done. Demography, clinical profile, triggers, electroencephalography (EEG), neuroimaging, treatment details and outcomes were analysed. Sixteen case series and 35 case reports with a total of 249 cases were analysed. 82% of cases were from paediatric age group. The female to male ratio was 3:1. Psychiatric deficits, movement disorders, seizures, and language abnormalities were the most common clinical features. MRI brain abnormalities were seen in 45% patients. Electroencephalographic abnormalities were seen in 85% of patients. Infective triggers (herpes simplex virus and various other agents) were reported in 11% of the cases. Pediatric patients as compared with adults had more encephalopathy, autonomic dysfunctions, and normal imaging whereas the latter had more cognitive dysfunctions and delta brush pattern in electroencephalography (p<0.005). Therefore, to conclude, this literature review suggests that overall, the clinical spectrum of Indian cases is like cases described from other parts of the world. However, most reported cases from India belonged to paediatric age group who had more encephalopathy, autonomic dysfunctions, and normal brain imaging compared to adults. A few novel infectious agents as triggers were described from India. [ABSTRACT FROM AUTHOR]

Early detection of megaloblastic anemia and associated neurological complications is crucial for management. This study was conducted to compare serum holotranscobalamin level with serum vitamin B12 level as early biomarker in people prone to megaloblastic anemia and to evaluate co-relation between these biomarkers and nerve conduction study in study patients. 83 adult patients (Hb > 12 gm/dl) prone to megaloblastic anemia were studied for basic haematological investigations, random blood sugar, thyroid function test, liver function test, kidney function test, serum vitamin B12, serum holotranscobalamin and serum folic acid levels. 45 patients among them underwent nerve conduction studies. All study patients were classified in 6 groups on the basis of risk factors for megaloblastic anemia. 29 patients (34.9%) were on antiepileptic drugs, 26 (31.3%) were chronic alcoholic, 10 patients (12%) each, had malabsorption and ileal tuberculosis, 6 (7.22%) had chronic pancreatitis and 2 (2.4%) had ileal resection. 30 patients (36.14%) had low serum holotranscobalamin, including 7 patients (8.43%) with low serum vitamin B12 level also, unmasking vitamin B12 deficiency in 23 patients (27.7%). 7 patients (8.43%) had mean corpuscular volume (MCV) > 100fL and 8 patients (9.63%) had vitamin B12 deficiency related changes on peripheral smear. Serum vitamin B12 and holotranscobalamin levels were significantly low in patients with peripheral smear changes, with p value 0.039 and 0.041 respectively, while no such association seen with MCV. Subclinical peripheral neuropathy was detected in 18 (40%) out of 45 patients on nerve conduction study. Serum holotranscobalamin levels were significantly lower (p = 0.031) than serum vitamin B12 levels (p = 0.2) in patients with neuropathic changes. Rest investigations and serum folic acid levels were normal in all patients. Holotranscobalamin levels can be considered early and reliable marker for vitamin B12 deficiency and deficiency associated peripheral neuropathy, even in patients who are prone to megaloblastic anemia, and not yet anemic or symptomatic for neuropathy. [ABSTRACT FROM AUTHOR]

Background: EMPOwER, a 12-week, double-blind (DB), randomized, placebo-controlled study evaluated the efficacy and safety of erenumab in adult patients with episodic migraine (EM) from Asia, the Middle East, and Latin America. This study analyzes the Indian experience for the use of erunumab for prevention of episodic migraine. Objective: The study aimed to evaluate the efficacy and tolerability of erenumab (70 mg and 140 mg) in EM patients from India. Methods: Randomized patients received monthly subcutaneous injections of placebo and erenumab 70 mg or 140 mg for 3 months. The primary endpoint was a change from the baseline in monthly migraine days (MMDs) at month 3. Other endpoints included achievement of ≥50%, ≥75%, and 100% reduction in MMD; a change in monthly acute migraine-specific medication treatment days; a change in patient-reported outcomes; and safety assessment. Results: Of the 539 patients screened, 351 patients were randomized (erenumab, 70 mg: n = 133 and 140 mg: n = 94; placebo: n = 124). The mean (±SD) age, disease duration, and MMD were 35.1 (±8.6) years, 6.77 (±6.01) years, and 7.82 (±2.89) days, respectively. The placebo-adjusted difference in mean MMD for erenumab 70 mg was -0.88 (95% CI, -2.16, 0.39; P = 0.174) days, and that for erenumab 140 mg was -1.01 (-2.42, 0.41; P = 0.164) days versus placebo. Secondary and exploratory endpoints demonstrated consistently better results in both erenumab dosage groups versus placebo. Treatment-emergent adverse events were comparable across groups (erenumab, 70 mg: 22.7% and 140 mg: 24.5%; placebo: 25.2%). Conclusion: Both doses of erenumab showed numerical improvement for efficacy endpoints and were well-tolerated in the Indian population. No new safety signals were reported. [ABSTRACT FROM AUTHOR]

Objectives: To assess the impact of lockdown during the COVID‐19 pandemic on migraine patients in India on disease activity, healthcare accessibility, and quality of life (QoL). Materials & Methods: This internet‐based survey study using a structured questionnaire was conducted from 27th April to 31st July 2020. Previous physician‐diagnosed migraine patients or those fulfilling any two of three clinical features (limitation of activities for >1 day, associated nausea or vomiting, and photophobia or phonophobia) were diagnosed as migraine patients. QoL was captured using a Likert scale and determinants of poor QoL were identified by logistic regression. Results: A total of 4078 persons completed the full survey out of which 984 (24.1%) had migraine (mean age 35.3 ±11.2). Compared to pre‐lockdown, 51.3% of migraineurs reported worsening of their headaches in terms of increased attack frequency (95.6%), increased headache days (95%), increased attack duration (89.9%) and increased headache severity (88.1%). The worsening was attributed to anxiety due to the pandemic (79.7%), inability or difficulty to access healthcare (48.4%) and migraine medicines (48.9%), and financial worries (60.9%). 26.8% of migraineurs reported poor QoL compared to 7.37% of non‐migraineurs [p<0.0001]. Migraine affected QoL in 61.4% of migraineurs. The predictors of poor QoL on logistic regression included worsening migraine during the lockdown (AOR 4.150; CI 2.704‐ 6.369) and difficulty accessing migraine medicines (AOR 4.549; CI 3.041‐ 6.805). Employment as an essential COVID‐19 worker (AOR 0.623; CI 0.409‐ 0.950) protected against poor QoL. Conclusions: COVID‐19 pandemic‐related lockdown greatly impacted migraine patients in India which significantly reduced their QoL. [ABSTRACT FROM AUTHOR]

We discuss computer simulations of a particle that hops forward and backward randomly on a one-dimensional lattice. To track the motion of the particle, we use a data acquisition protocol that mimics a virtual digital optical imaging system. Plots of the data extracted from these images yield a pattern that is similar to the patterns observed in real imaging of a moving particle in a living cell. To explore the physical origin of the observed patterns, we use different spatio-temporal resolutions and show that the characteristics of the observed patterns are determined by the spatial and temporal resolutions of the digital imaging device. The simulations help not only to determine the origin of these patterns in the imaging data, but also to avoid misinterpreting the imaging data in terms of a special property of the particle or its dynamics. [ABSTRACT FROM AUTHOR]

Background: The proximity of sensory neurons in the upper cervical spinal cord to the trigeminal nucleus caudalis (TNC) neurons and the convergence of sensory input to TNC neurons from both cervical and trigeminal fibers underscore the rationale of using greater occipital nerve block (GON-block) for acute and preventive treatment in various headache disorders.Objective: The aim of this study was to critically review the existing literature regarding the safety and efficacy of GON-block in various headache disorders.Methods: We searched the eligible studies in English by searching in PubMed till December 31, 2020 for randomized controlled trials (RCTs), observational studies, open-label studies, case series, and case reports on the efficacy and the safety of GON-block for the treatment of headache disorders using the keywords "greater occipital nerve block", "headache" and "treatment". Studies using combination of GON-block and other peripheral nerve blocks (PNBs) and C2/C3 blocks were excluded.Results: Seventy-two eligible studies were reviewed. Based on RCTs and open-label studies, good evidence of the efficacy of GON-block was found for migraine, cluster headache (CH), post-dural puncture headache (PDPH), cervicogenic headache (CGH), and occipital neuralgia (ON). The analgesic effect of GON-block outlasted its anesthetic effect by days to weeks. Evidence for acute and short-term (transitional) treatment was more robust than for long-term prevention. GON-block was found to be safe and the treatment-emergent adverse effects (TEAEs) were generally mild and transient.Conclusion: GON-block is a useful modality of treatment in various headache disorders because of many attractive features such as its early effect in reducing the severity of pain, sustained effect following a single injection, easy technique, minimum invasiveness, minimum TEAE, no drug-to-drug interactions, and negligible cost. [ABSTRACT FROM AUTHOR]

Background: Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache with autonomic symptoms (SUNA) are rare and disabling primary headache disorders that are subtypes of Short-lasting unilateral neuralgiform headache attacks (SUNHA).Aim: The aim of this narrative review was to provide a comprehensive update on headache phenotype, pathophysiology, and various treatment options available for SUNCT and SUNA.Methods: References for this review were identified by searches of articles published in the English language in PubMed between 1978 and October 2020 using "short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT)", "short-lasting unilateral neuralgiform headache with autonomic symptoms (SUNA)", "short-lasting unilateral neuralgiform headache attacks (SUNHA)", "trigeminal autonomic cephalalgias" as keywords in various combinations.Results: Of a potential 1103 articles, seven case series describing clinical characteristics of SUNCT/SUNA patients were identified for this review. For symptomatic/secondary SUNCT/SUNA, 53 individual case reports, and one case series were reviewed. One placebo-controlled trial and 11 open-label case series that evaluated various medical and surgical treatments in SUNCT/SUNA were also reviewed. Available literature suggests that SUNCT and SUNA are subtypes of the same disorder characterized by severe side locked short duration headache with ipsilateral prominent cranial autonomic symptoms and signs. Pathophysiology may involve both peripheral and central mechanisms. Lamotrigine is the most effective preventive therapy while intravenous lidocaine is the most efficacious drug as transitional therapy for severe disabling attacks. Surgical options including microvascular decompression in those having neurovascular conflict, occipital nerve stimulation, and hypothalamic deep brain stimulation can be alternative treatment options for medically refractory patients. [ABSTRACT FROM AUTHOR]

Background: Tension-type headache (TTH) is the most common form of primary headache.Objective: The aim of this study was to document and summarize the advances in the understanding of TTH in terms of pathogenesis and management.Material and Methods: We reviewed the available literature on the pathogenesis and management of TTH by searches of PubMed between 1969 and October 2020, and references from relevant articles. The search terms "tension-type headache", "episodic tension-type headache", chronic tension-type headache, "pathophysiology", and "treatment" were used.Results: TTH occurs in two forms: episodic TTH (ETTH) and chronic TTH (CTTH). Unlike chronic migraine, CTTH has been less thoroughly studied and is a more difficult headache to treat. Frequent ETTH and CTTH are associated with significant disability. The pathogenesis of TTH is multifactorial and varies between the subtypes. Peripheral mechanism (myofascial nociception) and environmental factors are possibly more important in ETTH, whereas genetic and central factors (sensitization and inadequate endogenous pain control) may play a significant role in the chronic variety. The treatment of TTH consists of pharmacologic and non-pharmacologic approaches. Simple analgesics like NSAIDs are the mainstays for acute management of ETTH. CTTH requires a multimodal approach. Preventive drugs like amitriptyline or mirtazapine and non-pharmacologic measures like relaxation and stress management techniques and physical therapies are often combined. Despite these measures, the outcome remains unsatisfactory in many patients.Conclusion: There is clearly an urgent need to understand the pathophysiology and improve the management of TTH patients, especially the chronic form. [ABSTRACT FROM AUTHOR]

Headache disorders, characterized by recurrent headache, are among the most common disorders of the nervous system. The aim of this study was to document epidemiological and economic burden due to headache globally and in India and suggest a public health approach to address headache disorders for India. We reviewed the available literature on burden due to headache, its management using a primary health care approach and health system barriers, with special emphasis on India. Globally, it has been estimated that prevalence of current headache disorder (symptomatic within last year) among adults is about 50%, around 30% report migraine and headache on 15 or more days every month affects 1.7-4% people. The Global Burden of Disease Study 2016 estimated that migraine caused 45·1 million (95% UI 29·0-62·8) and tension-type headache 7·2 million (95% UI 4·6-10·5) years of life lived with disability. Limited data available in India support such high burden. These studies also indicate high diagnostic and treatment gaps for headache disorders in India. Major challenges in addressing headache disorders effectively in India are low perceived severity, absence of burden data, lack of standard treatment protocols for headache disorders and primary care models for neurological disorders in developing country context. There needs to be a better appreciation of the burden and a public health approach among all stakeholders, if burden of headache disorders is to be addressed effectively in India. [ABSTRACT FROM AUTHOR]

Background: Stroke is the second leading cause of death globally and it is a major cause of long-term, physical, psychological, and social disability among the elderly. Increasing evidence shows that ischemic injury and inflammation account for its pathogenic progression. So, we studied the association of Intercellular Adhesion Molecule 1 (ICAM1) polymorphism with ischemic stroke, stroke severity, and outcome. Aims and Objectives: To compare ICAM1 469 E/K polymorphism in ischemic stroke patients with healthy controls, and to study its association with stroke severity and outcome. Materials and Methods: Fifty patients of ischemic stroke and hundred healthy individuals were included. The stroke severity was assessed clinically and radiologically. Outcome was measured at three and six months of stroke onset. Genomic DNA was used for Allele-Specific PCR to detect ICAM1 469 E/K polymorphism. The subjects were categorized into EE, EK, and KK genotypes. Results: The odds of EK genotype to develop stroke was 0.41 (95 % CI; 0.17 - 0.92) (p = 0.07) and of KK genotype was 0.41 (95 % CI; 0.11 - 0.87) (p = 0.04) compared to EE genotype. Subjects with ICAM1K allele had significantly reduced risk of stroke compared with those with E allele. (RR: 0.55; 95% CI: 0.35-0.87) (p=0.03). Conclusion: Subjects with ICAM1K allele had significantly reduced the risk of developing stroke. 469 E/K polymorphism of the ICAM1 gene does not significantly affect stroke severity, mortality, and outcome. [ABSTRACT FROM AUTHOR]

Flagella of eukaryotic cells are transient long cylindrical protrusions. The proteins needed to form and maintain flagella are synthesized in the cell body and transported to the distal tips. What 'rulers' or 'timers' a specific type of cells use to strike a balance between the outward and inward transport of materials so as to maintain a particular length of its flagella in the steady state is one of the open questions in cellular self-organization. Even more curious is how the two flagella of biflagellates, like Chlamydomonas reinhardtii, communicate through their base to coordinate their lengths. In this paper we develop a stochastic model for flagellar length control based on a time-of-flight (ToF) mechanism. This ToF mechanism decides whether or not structural proteins are to be loaded onto an intraflagellar transport (IFT) train just before it begins its motorized journey from the base to the tip of the flagellum. Because of the ongoing turnover, the structural proteins released from the flagellar tip are transported back to the cell body also by IFT trains. We represent the traffic of IFT trains as a totally asymmetric simple exclusion process (TASEP). The ToF mechanism for each flagellum, together with the TASEP-based description of the IFT trains, combined with a scenario of sharing of a common pool of flagellar structural proteins in biflagellates, can account for all key features of experimentally known phenomena. These include ciliogenesis, resorption, deflagellation as well as regeneration after selective amputation of one of the two flagella. We also show that the experimental observations of Ishikawa and Marshall are consistent with the ToF mechanism of length control if the effects of the mutual exclusion of the IFT trains captured by the TASEP are taken into account. Moreover, we make new predictions on the flagellar length fluctuations and the role of the common pool. [ABSTRACT FROM AUTHOR]

The article presents a case study related to 23-year-old male who presented with insidious onset, gait imbalance and bladder dysfunction, in the form of frequency, and urge incontinence of three months duration. Topics inlcude the pathophysiology being hitherto unknown but hypersensitivity to tuberculin protein has been postulated the polymerase chain reaction studies, and the pattern of cord involvement with presence of hemorrhages in the fundus not favor a diagnosis of Multiple Sclerosis.

COVID-19 pandemic is an emerging, rapidly evolving situation. Migraine is one of the commonest and highly disabling chronic neurological diseases in the world. During the pandemic and lockdown, migraine patients are facing an enormous problem in getting optimum care because of difficulty in access, forced social isolation, and encountering a health system that is getting rapidly overwhelmed. It is important that they must be protected by minimizing their visits to the clinics and emergency departments. Paradoxically multiple triggers are in operation which is likely to increase their headache frequency. Hence physicians should be made aware of the new rules of the game in treating migraines during this time of the pandemic so that these patients get optimum treatment and care and don't feel left out. This review tries to answer a series of questions related to managing migraines in the times of COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Presents the results of the Monte carlo simulations of gemini surfactants lattice models. Examination of critical micellar concentration variations; Clarification on geometrical shape, size and density of surfactant molecules; Influence of ionic charge on variation of critical micellar concentration with spacer length.

We investigate the equilibrium structure as well as a specific dynamical aspect of thin films of complex fluids containing amphiphilic membranes. We explore the structures of ternary microemulsions, confined in a pore, resulting from various different types of interactions of the confining wall with the molecules. We compute the concentration profiles of the three components, namely, oil, water and amphiphiles, by carrying out extensive Monte Carlo simulations of the Widom model and its recently proposed generalizations on a simple-cubic lattice of size Lx×Ly×Lz under appropriate boundary conditions. We investigate both the wide-gap geometry (Lx=Ly[bar_over_tilde:_approx._equal_to]Lz>1) and narrow-gap geometry (Lx=Ly>Lz). We observe novel concentration profiles in the narrow-gap geometry when Lz is of the order of a few molecular layers (i.e., in micropores). We also compute the lifetime of thermodynamically unstable bilayers of a specific initial conformation in the Widom model of microemulsions. For identical initial conformations of these model bilayers, we study the dependence of the lifetime on (a) the initial concentration of the amphiphilic molecules, (b) the temperature, (c) the curvature elasticity of the amphiphilic membrane, and (d) the thickness of water layers inside the two constituent monolayers. We also compare the models and results in our computer experiment with those in the laboratory experiment on the rupture of the Newton black films and common black films. [ABSTRACT FROM AUTHOR]

Peripheral neuropathy is a common reason for referral to neurology. Chronic acquired demyelinating neuropathies are an important and varied group with overlapping presentations, and may have an immune-mediated cause. Their correct diagnosis is important as they respond to different treatments; timely intervention can prevent irreversible axonal degeneration. We present a case that highlights the approach to an adult presenting with a chronic demyelinating neuropathy. [ABSTRACT FROM AUTHOR]

The Michaelis-Menten (MM) fundamental formula describes how the rate of enzyme catalysis depends on substrate concentration. The familiar hyperbolic relationship was derived by timescale separation for a network of three reactions. The same formula has subsequently been found to describe steady-state input-output responses in many biological contexts, including single-molecule enzyme kinetics, gene regulation, transcription, translation, and force generation. Previous attempts to explain its ubiquity have been limited to networks with regular structure or simplifying parametric assumptions. Here, we exploit the graph-based linear framework for timescale separation to derive general structural conditions under which the MM formula arises. The conditions require a partition of the graph into two parts, akin to a "coarse graining" into the original MM graph, and constraints on where and how the input variable occurs. Other features of the graph, including the numerical values of parameters, can remain arbitrary, thereby explaining the formula's ubiquity. For systems at thermodynamic equilibrium, we derive a necessary and sufficient condition. For systems away from thermodynamic equilibrium, especially those with irreversible reactions, distinct structural conditions arise and a general characterization remains open. Nevertheless, our results accommodate, in much greater generality, all examples known to us in the literature. [ABSTRACT FROM AUTHOR]

Primary trigeminal autonomic cephalalgias (TACs) are uncommon group of headache disorders. These are defined and diagnosed by the criteria given by the International Classification of Headache Disorders 3β version. Over the past few decades, a number of secondary (symptomatic) cases have been described in the literature with headache features indistinguishable from primary TACs. Many structural and other pathologies have been found in these patients that can be causally related to the headaches. This review attempts to critically analyze the existing literature including the new cases published during 2015-2017. [ABSTRACT FROM AUTHOR]

The sequence of amino acid monomers in the primary structure of a protein is decided by the corresponding sequence of codons (triplets of nucleic acid monomers) on the template messenger RNA (mRNA). The polymerization of a protein, by incorporation of the successive amino acid monomers, is carried out by a molecular machine called ribosome. We develop a stochastic kinetic model that captures the possibilities of mis-reading of mRNA codon and prior mis-charging of a tRNA. By a combination of analytical and numerical methods, we obtain the distribution of the times taken for incorporation of the successive amino acids in the growing protein in this mathematical model. The corresponding exact analytical expression for the average rate of elongation of a nascent protein is a 'biologically motivated' generalization of the Michaelis-Menten formula for the average rate of enzymatic reactions. This generalized Michaelis-Menten-like formula (and the exact analytical expressions for a few other quantities) that we report here display the interplay of four different branched pathways corresponding to selection of four different types of tRNA. [ABSTRACT FROM AUTHOR]

Intensive care is a specialized branch of medicine dealing with the diagnosis, management, and follow up of critically ill or critically injured patients. It requires input from other branches of medicine on various issues. A critical care specialist has expertise in managing such patients round the clock. Based on his freedom to take decisions in the intensive care unit (ICU), different types of ICUs - open, closed, or semi-closed - have been defined. There is no doubt that all critical patients should be evaluated by an intensivist. Therefore, it is argued that a closed ICU model would be the ideal model. However, this may not always be feasible and other models may be more useful in resource-limited countries. In this review, we compare the different formats of ICU functioning and their suitability in different hospitals. [ABSTRACT FROM AUTHOR]