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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]

Background: Greater occipital nerve blockade for the prevention of chronic migraine has a limited evidence base. A robust randomized double-blind, placebo-controlled trial is needed. Methods: This double-blind, placebo-controlled, parallel-group trial, following a baseline period of four weeks, randomly assigned patients of chronic migraine 1:1 to receive four-weekly bilateral greater occipital nerve blockade with either 2 ml of 2% (40 mg) lidocaine (active group) or 2 ml of 0.9% saline (placebo) injections for 12 weeks. The primary and key secondary efficacy endpoints were a change from the baseline in the mean number of headache and migraine days and the achievement of ≥50% reduction in headache days from baseline across the weeks 9–12 respectively. Safety evaluations included the documentation and reporting of serious and other adverse events. Results: Twenty-two patients each were randomly allocated to the active and placebo group. Baseline demography and clinical characteristics were similar between the two groups. Mean headache and migraine days at baseline (±SD) were 23.4 ± 4.4 and 15.6 ± 5.7 days in the active group and 22.6 ± 5.0 and 14.6 ± 4.6 days in the placebo group respectively. The active group compared to the placebo had a significantly greater least-squares mean reduction in the number of headache and migraine days (−4.2 days [95% CI: −7.5 to −0.8; p = 0.018] and −4.7 days [95%CI: −7.7 to −1.7; p = 0.003] respectively). 40.9% of patients in the active group achieved ≥50% reduction in headache days as compared with 9.1% of patients receiving a placebo (p = 0.024). Overall, 64 mild and transient adverse events were reported by 16 patients in the active group and 15 in the placebo. No death or serious adverse events were reported. Conclusion: Four-weekly greater occipital nerve blockade with 2% lidocaine for 12 weeks was superior to placebo in decreasing the average number of headache and migraine days in patients with chronic migraine with a good tolerability profile. Clinical trial.gov no. CTRI 2020/07/026709 [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]

Living cells use long tubular appendages for locomotion and sensory purposes. Hence, assembling and maintaining a protrusion of correct length is crucial for survival and overall performance. Usually the protrusions lack the machinery for the synthesis of building blocks and imports them from the cell body. What are the unique features of the transport logistics which facilitate the exchange of these building blocks between the cell and the protrusion? What kind of 'rulers' and 'timers' does the cell use for constructing its appendages of correct length on time? How do the multiple appendages coordinate and communicate among themselves during different stages of their existence? How frequently do the fluctuations drive the length of these dynamic protrusions out of the acceptable bounds? These questions are addressed from a broad perspective in this review which is organized in three parts. In part-I the list of all known cell protrusions is followed by a comprehensive list of the mechanisms of length control of cell protrusions reported in the literature. We review not only the dynamics of the genesis of the protrusions, but also their resorption and regrowth as well as regeneration after amputation. As a case study in part-II, the specific cell protrusion that has been discussed in detail is eukaryotic flagellum (also known as cilium); this choice was dictated by the fact that flagellar length control mechanisms have been studied most extensively over more than half a century in cells with two or more flagella. Although limited in scope, brief discussions on a few non-flagellar cell protrusions in part-III of this review is intended to provide a glimpse of the uncharted territories and challenging frontiers of research on subcellular length control phenomena that awaits rigorous investigations. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy and tolerability of combination treatment of topiramate and greater occipital nerve block to topiramate monotherapy in adult chronic migraine patients. Background: Options for the preventive treatment of chronic migraine are limited and costly. Combination treatments do not have an evidence base yet. Methods: This was a parallel group, 3 arms with 1:1:1 allocation ratio randomized controlled study in consecutive adult chronic migraine patients attending Headache Clinic in a tertiary care hospital. Patients received either topiramate monotherapy 100 mg/day (group A), or topiramate plus greater occipital nerve block with 40 mg lidocaine (2%) and 80mg (2 ml) methylprednisolone as the first injection followed by monthly injections of lidocaine for the next 2 months (group B) or topiramate plus greater occipital nerve block with 40 mg lidocaine (2%) injections monthly for 3 months (group C). The primary endpoint was the mean change in monthly migraine days at Month 3. Multiple secondary endpoints were assessed that included among others, achievement of ≥50% reduction in mean monthly headache days compared to baseline at Month 3 and assessment for any adverse events. Results: One hundred and twenty-five patients were randomized; 41 to group A, 44 to group B, and 40 to group C. Efficacy assessments were done for 121 patients. Patients receiving combination treatment of topiramate and greater occipital nerve block with steroids and lidocaine and greater occipital nerve block with only lidocaine compared to topiramate monotherapy showed greater reductions in monthly migraine days at Month 3 (−9.6 vs −7.3 days; p = 0.003) and (−10.1 vs −7.3 days; p < 0.001) respectively. Greater proportion of patients in both the combination treatment groups (added greater occipital nerve block with and without steroid) achieved ≥50% reduction in mean monthly headache days [71.4% vs 39%; OR (95% CI) 3.9(1.6–9.8); p = 0.004] and [62.4% vs 39%; OR (95% CI) 2.7(1.1–6.7); p = 0.034] respectively, compared to those receiving topiramate monotherapy. Adverse effects between the groups were comparable although patients receiving combination treatment with added greater occipital nerve block reported transient adverse effects like post-injection dizziness, local site swelling, and pain. No serious adverse event was reported. Conclusion: Combination treatments of topiramate with monthly injections of greater occipital nerve block were more effective in reducing monthly migraine days in chronic migraine than topiramate monotherapy at Month 3. Combination treatments were well tolerated. [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]

Objective: The aim of the TOP-PRO-study, a double-blind randomized controlled trial, was to assess the efficacy (non-inferiority) and tolerability of propranolol compared to topiramate for the prevention of chronic migraine. Background: Except for topiramate, oral preventive treatment for chronic migraine lacks credible evidence. Methods: Chronic migraine patients aged above 18 years and less than 65 years of age, not on any preventive treatment were randomly allocated to receive topiramate (100 mg/day) or propranolol (160 mg/day). The primary efficacy outcome was the mean change in migraine days per 28 days at the end of 24 weeks from baseline. A mean difference of 1.5 days per four weeks was chosen as the cut-off delta value. Multiple secondary efficacy outcomes and treatment emergent adverse events were also assessed. Results: As against the planned sample size of 244, only 175 patients could be enrolled before the spread of the corona virus disease-2019 pandemic and enforcement of lockdown in India. Of the 175 randomized patients, 95 (topiramate 46 and propranolol 49) completed the trial. The mean change in migraine days was −5.3 ± 1.2 vs −7.3 ± 1.1 days (p = 0.226) for topiramate and propranolol groups respectively. Propranolol was found to be non-inferior and not superior to topiramate (point estimate of −1.99 with a 95% confidence interval of −5.23 to 1.25 days). Multiple secondary outcomes also did not differ between the two groups. Intention to treat analysis of 175 patients and per-protocol analysis of 95 patients yielded concordant results. There was no significant difference in the incidence of adverse events between the two groups. Conclusion: Propranolol (160mg/day) was non-inferior, non-superior to topiramate (100mg/day) for the preventive treatment of chronic migraine and had a comparable tolerability profile. Trial Registration: Clinical Trials Registry-India CTRI/2019/05/018997) [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]

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]

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]

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]

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]

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.

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]

We study the flux of totally asymmetric simple exclusion processes (TASEPs) on a twin co-axial square tracks. In this biologically motivated model the particles in each track act as mobile bottlenecks against the movement of the particles in the other although the particles are not allowed to move out of their respective tracks. So far as the outer track is concerned, the particles on the inner track act as bottlenecks only over a set of fixed segments of the outer track, in contrast to site-associated and particle-associated quenched randomness in the earlier models of disordered TASEP. In a special limiting situation the movement of particles in the outer track mimic a TASEP with a “point-like” immobile (i.e., quenched) defect where phase segregation of the particles is known to take place. The length of the inner track as well as the strength and number density of the mobile bottlenecks moving on it are the control parameters that determine the nature of spatio-temporal organization of particles on the outer track. Variation of these control parameters allows variation of the width of the phase-coexistence region on the flux–density plane of the outer track. Some of these phenomena are likely to survive even in the future extensions intended for studying traffic-like collective phenomena of polymerase motors on double-stranded DNA. [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]

Cytoskeletal motor proteins move on filamentous tracks by converting input chemical energy that they derive by catalyzing the hydrolysis of ATP. The ATPase site is the analogue of an engine and hydrolysis of ATP is the analogue of burning of chemical fuel. Moreover, the functional role of a segment of the motor is analogous to that of the transmission system of an automobile, which consists of a shaft, gear, clutch, etc. The operation of the engine is intrinsically 'noisy' and the motor faces a molecular 'hailstorm' in the aqueous medium. In this commemorative review, we celebrate the centenary of Michaelis and Menten's landmark paper of 1913 and the golden jubilee of Monod and colleagues classic paper of 1963 by highlighting their relevance with respect to explaining the operational mechanisms of the engine and the transmission system, respectively, of cytoskeletal motors. [ABSTRACT FROM AUTHOR]

Abstract: A molecular motor is made of either a single macromolecule or a macromolecular complex. Just like their macroscopic counterparts, molecular motors “transduce” input energy into mechanical work. All the nano-motors considered here operate under isothermal conditions far from equilibrium. Moreover, one of the possible mechanisms of energy transduction, called Brownian ratchet, does not even have any macroscopic counterpart. But, molecular motor is not synonymous with Brownian ratchet; a large number of molecular motors execute a noisy power stroke, rather than operating as Brownian ratchet. We review not only the structural design and stochastic kinetics of individual single motors, but also their coordination, cooperation and competition as well as the assembly of multi-module motors in various intracellular kinetic processes. Although all the motors considered here execute mechanical movements, efficiency and power output are not necessarily good measures of performance of some motors. Among the intracellular nano-motors, we consider the porters, sliders and rowers, pistons and hooks, exporters, importers, packers and movers as well as those that also synthesize, manipulate and degrade “macromolecules of life”. We review mostly the quantitative models for the kinetics of these motors. We also describe several of those motor-driven intracellular stochastic processes for which quantitative models are yet to be developed. In part I, we discuss mainly the methodology and the generic models of various important classes of molecular motors. In part II, we review many specific examples emphasizing the unity of the basic mechanisms as well as diversity of operations arising from the differences in their detailed structure and kinetics. Multi-disciplinary research is presented here from the perspective of physicists. [Copyright &y& Elsevier]

DNA, RNA and proteins are among the most important macromolecules in a living cell. These molecules are polymerized by molecular machines. These natural nano-machines polymerize such macromolecules, adding one monomer at a time, using another linear polymer as the corresponding template. The machine utilizes input chemical energy to move along the template which also serves as a track for the movements of the machine. In the Alan Turing year 2012, it is worth pointing out that these machines are "tape-copying Turing machines". We review the operational mechanisms of the polymerizer machines and their collective behavior from the perspective of statistical physics, emphasizing their common features in spite of the crucial differences in their biological functions. We also draw the attention of the physics community to another class of modular machines that carry out a different type of template-directed polymerization. We hope this review will inspire new kinetic models for these modular machines. [ABSTRACT FROM AUTHOR]

Tension type headaches are common in clinical practice. Earlier known by various names, the diagnosis has had psychological connotations. Recent evidence has helped clarify the neurobiological basis and the disorder is increasingly considered more in the preview of neurologists. The classification, clinical features, differential diagnosis and treatment of tension type headache are discussed in this paper. [ABSTRACT FROM AUTHOR]

DNA polymerase (DNAP) is a dual-purpose enzyme that plays two opposite roles in two different situations during DNA replication. It plays its a normal role as a polymerase catalyzing the elongation of a new DNA molecule by adding a monomer. However, it can switch to the role of an exonuclease and shorten the same DNA by cleavage of the last incorporated monomer from the nascent DNA. Just as misincorporated nucleotides can escape exonuclease causing a replication error, the correct nucleotide may get sacrificed unnecessarily by erroneous cleavage. The interplay of polymerase and exonuclease activities of a DNAP is explored here by developing a minimal stochastic kinetic model of DNA replication. Exact analytical expressions are derived for a few key statistical distributions; these characterize the temporal patterns in the mechanical stepping and the chemical (cleavage) reaction. The Michaelis-Menten-like analytical expression derived for the average rates of these two processes not only demonstrate the effects of their coupling, but are also utilized to measure the extent of replication error and erroneous cleavage. [ABSTRACT FROM AUTHOR]

Abstract: The process of polymerizing a protein by a ribosome, using a messenger RNA (mRNA) as the corresponding template, is called translation. Ribosome may be regarded as a molecular motor for which the mRNA template serves also as the track. Often several ribosomes may translate the same (mRNA) simultaneously. The ribosomes bound simultaneously to a single mRNA transcript are the members of a polyribosome (or, simply, polysome). Experimentally measured polysome profile gives the distribution of polysome sizes. Recently a breakthrough in determining the instantaneous positions of the ribosomes on a given mRNA track has been achieved and the technique is called ribosome profiling (). Motivated by the success of these techniques, we have studied the spatio-temporal organization of ribosomes by extending a theoretical model that we have reported elsewhere (). This extended version of our model incorporates not only (i) mechano-chemical cycle of individual ribomes, and (ii) their steric interactions, but also (iii) the effects of (a) kinetic proofreading, (b) translational infidelity, (c) ribosome recycling, and (d) sequence inhomogeneities. The theoretical framework developed here will serve in guiding further experiments and in analyzing the data to gain deep insight into various kinetic processes involved in translation. [Copyright &y& Elsevier]

All living creatures are made of cells. The cell is the structural and functional unit of life. This Resource Letter serves as a guide to the literature on nano-machines, which drive not only intracellular movements but also motility of the cell. These machines are usually proteins or macromolecular assemblies that require appropriate fuel for their operations. Although, traditionally, these machines were subjects of investigation in biology and biochemistry, increasing use of the concepts and techniques of physics in recent years have contributed to the quantitative understanding of the fundamental principles underlying their operational mechanisms. The possibility of exploiting these principles for the design and control of artificial nanomachines has opened up a new frontier in the bottom-up approach to nanotechnology. [ABSTRACT FROM AUTHOR]

Proteins are polymers of amino acids. These macromolecules are synthesized by intracellular machines called ribosomes. Although the experimental investigation of protein synthesis has been a traditional area of research in molecular cell biology, important quantitative models of protein synthesis have been reported in research journals devoted to statistical physics and related interdisciplinary topics. From the perspective of a physicist, protein synthesis is the classical transport of interacting ribosomes on a messenger RNA (mRNA) template that dictates the sequence of the amino acids on the protein. We discuss appropriate simplification of the models and methods. In particular, we develop and analyze a simple toy model using some elementary techniques of nonequilibrium statistical mechanics and predict the average rate of protein synthesis and the spatial organization of the ribosomes in the steady state. [ABSTRACT FROM AUTHOR]

In the current issue, in a paper titled "Investigation of the association between headache type, frequency, and clinical and radiological findings in patients with multiple sclerosis",[[1]] the authors assessed 320 patients of multiple sclerosis (MS) and found that primary headache was present in 54.4% of the patients [migraine in 30.6% and tension-type headache (TTH) in 23.8%)] at the time of admission. The high prevalence of headache in MS patients makes us ponder whether this is just a comorbid association or is a primary symptom of MS. It has been postulated that these may be responsible for meningeal inflammation and can trigger headaches, particularly migraine in MS patients.[[4]] Locations of the MS plaques in the brain may also be important. [Extracted from the article]

Abstract: Molecular motors do not work in isolation in-vivo. We highlight some of the coordinations, cooperations and competitions that determine the collective properties of molecular motors in eukaryotic cells. In the context of traffic-like movement of motors on a track, we emphasize the importance of single-motor bio-chemical cycle and enzymatic activity on their collective spatio-temporal organization. Our modelling strategy is based on a synthesis—the same model describes the single-motor mechano-chemistry at sufficiently low densities whereas at higher densities it accounts for the collective flow properties and the density profiles of the motors. We consider two specific examples, namely, traffic of single-headed kinesin motors KIF1A on a microtubule track and ribosome traffic on a messenger RNA track. [Copyright &y& Elsevier]

Abstract: Ecology and evolution are inseparable. Motivated by some recent experiments, we have developed models of evolutionary ecology from the perspective of dynamic networks. In these models, in addition to the intra-node dynamics, which corresponds to an individual-based population dynamics of species, the entire network itself changes slowly with time to capture evolutionary processes. After a brief summary of our recent published works on these network models of eco-systems, we extend the most recent version of the model incorporating predators that wander into neighbouring spatial patches for food. [Copyright &y& Elsevier]

We propose a generic model of eco-systems, with a hierarchical food web structure. In our computer simulations, we let the eco-system evolve continuously for so long that we can monitor extinctions as well as speciations over geological time scales. Speciation leads not only to horizontal diversification of species at any given trophic level but also to vertical bio-diversity that accounts for the emergence of complex species from simpler forms of life. We find that five or six trophic levels appear as the eco-system evolves for sufficiently long time, starting initially from just one single level. Moreover, the time intervals between the successive collections of ecological data is so short that we could also study “micro”-evolution of the eco-system, i.e., the birth, ageing and death of individual organisms. [Copyright &y& Elsevier]

Flocks of birds and schools of fish are familiar examples of spatial patterns formed by living organisms. In contrast to the patterns on the skins of, say, zebras and giraffes, the patterns of our interest are transient although different patterns change over different timescales. The aesthetic beauty of these patterns has attracted the attention of poets and philosophers for centuries. Scientists from various disciplines, however, are in search of common underlying principles that give rise to the transient patterns in colonies of organisms. Such patterns are observed not only in colonies of organisms as simple as single-cell bacteria, but also in social insects like ants and termites. They are also observed in colonies of vertebrates as complex as birds and fish, and in human societies. In recent years, physicists have utilized the framework of statistical physics to understand these patterns. In this article, we present an overview emphasizing the common trends that rely on theoretical modeling of these systems using the so-called agent-based Lagrangian approach. [ABSTRACT FROM AUTHOR]

Very recently we developed a dynamic network model for eco-systems that achieved “unification” of “micro” and “macro”-evolution. We now propose an extension of our model so as to stabilize the eco-system and describe speciation in a more realistic manner. [Copyright &y& Elsevier]

The Sole–Manrubia model of “macro”-evolution describes the origination, evolution and extinction of species on geological time scales. We report some properties of this model which provide deep insight into this simple model which captures several realistic features. [Copyright &y& Elsevier]

How does a cell self-organize so that its appendages attain specific lengths that are convenient for their respective functions? What kind of 'rulers' does a cell use to measure the length of these appendages? How does a cell transport structure building materials between the cell body and distal tips of these appendages so as to regulate their dynamic lengths during various stages of its lifetime? Some of these questions are addressed here in the context of a specific cell appendage called flagellum (also called cilium). A "time of flight" (ToF) mechanism, adapted from the pioneering idea of Galileo, has been used successfully very recently to explain the length control of flagella by a biflagellate green algae. Using the same ToF mechanism, here we develop a stochastic model for the dynamics of flagella in two different types of monoflagellate unicellular organisms. A unique feature of these monoflagellates is that these become transiently multi-flagellated during a short span of their life time. The mean length of the flagella in our model reproduce the trend of their temporal variation observed in experiments. Moreover, for probing the intracellular molecular communication between the dynamic flagella of a given cell, we have computed the correlation in the fluctuations of their lengths during the multiflagellated stage of the cell cycle by Monte Carlo simulation. • Cellular length sensing ruler is actually a timer based on a time-of-flight mechanism. • The rate of dispatch of structure-building material from the base is length-dependent. • The motorized transport system in the tubular flagellum is collectively akin to a TASEP. • Monoflagellate cell becomes transiently multi-flagellated just before its division. • The model describes flagellar elongation kinetics and the correlations of length fluctuations. [ABSTRACT FROM AUTHOR]

The article offers information on the monograph titled "Researches on Irritability of Plants" by biologist Jagadis Chandra Bose published in 1913. According to Bose, plants are affected by storm, sunshine, drought and rain. Bose states that for the study of excitatory reactions of the plant, time elapses between the incidents of the shock and the initiation of a responsive movement should be determined.

An introduction is presented in which the editor discusses the contents within the issue including articles on topics such as trigeminal autonomic cephalalgias (TACs), the diagnostic criteria of TACs and the treatment of cluster headache (CH).

The article focuses on the medical condition of Superficial siderosis (SS) which is a degerative disorder with progressive cerebellar araxia and sensorineural hearing loss and is caused by pathological deposit on iron in certain parts of the human brain and structures which are in contact with cerebrospinal fluid (CSF).

The totally asymmetric simple exclusion process was originally introduced as a model for the trafficlike collective movement of ribosomes on a messenger RNA (mRNA) that serves as the track for the motorlike forward stepping of individual ribosomes. In each step, a ribosome elongates a protein by a single unit using the track also as a template for protein synthesis. But, prefabricated functionally competent ribosomes are not available to begin synthesis of protein; a subunit directionally scans the mRNA in search of the predesignated site where it is supposed to bind with the other subunit and begin the synthesis of the corresponding protein. However, because of "leaky" scanning, a fraction of the scanning subunits miss the target site and continue their search beyond the first target. Sometimes such scanners successfully identify the site that marks the site for initiation of the synthesis of a different protein. In this paper, we develop an exclusion model with three interconvertible species of hard rods to capture some of the key features of these biological phenomena and study the effects of the interference of the flow of the different species of rods on the same lattice. More specifically, we identify the mean time for the initiation of protein synthesis as appropriate mean first-passage time that we calculate analytically using the formalism of backward master equations. Despite the approximations made, our analytical predictions are in reasonably good agreement with the numerical data that we obtain by performing Monte Carlo simulations. [ABSTRACT FROM AUTHOR]