Comparative efficacy, quality of life, safety, and tolerability of atogepant and rimegepant in migraine prevention: A matching-adjusted indirect comparison analysis.

BACKGROUND: Comparative evaluations of preventive migraine treatments can help inform clinical decision making for managing migraine in clinical practice. METHODS: An anchored matching-adjusted indirect comparison analysis was conducted using pooled participant-level data from two phase 3 atogepant trials (ADVANCE and PROGRESS) and one phase 2/3 rimegepant trial (BHV3000-305) to evaluate the relative efficacy and safety/tolerability of atogepant and rimegepant as preventive migraine treatments. Participants receiving atogepant 60 mg once daily, rimegepant orally disintegrating tablet 75 mg once every other day, and placebo were included. Only participants meeting the BHV3000-305 inclusion/exclusion criteria were analyzed: ≥6 monthly migraine days and ≤18 monthly headache days at baseline. The primary efficacy assessment of interest was change in monthly migraine days across weeks 1-12. RESULTS: There were 252 participants in the atogepant group and 348 in the rimegepant group. Across weeks 1-12, atogepant 60 mg demonstrated a significantly greater reduction in mean monthly migraine days compared with rimegepant 75 mg (mean difference [95% CI]: -1.65 [-2.49, -0.81]; p < 0.001). Both atogepant and rimegepant demonstrated similar safety/tolerability profiles. CONCLUSION: In this matching-adjusted indirect comparison analysis, oral atogepant 60 mg once daily demonstrated a significantly greater reduction in monthly migraine days compared with rimegepant 75 mg orally disintegrating tablet once every other day.

Tuneable quantised conductance memory states in TiO2based resistive switching devices in crossbar geometry for high density memory applications.

The tunability and controllability of conductance quantization mediated multilevel resistive switching (RS) memory devices, fabricated in crossbar geometry can be a promising alternative for boosting storage density. Here, we report fabrication of Cu/TiO2/Pt based RS devices in 8 × 8 crossbar geometry, which showed reliable bipolar RS operations. The crossbar devices showed excellent spatial and temporal variability, time retention and low switching voltage (<1 V) and current (∼100µA). Furthermore, during the reset switching, highly repeatable and reliable integral and half-integral quantized conductance (QC) was observed. The observed QC phenomenon was attributed to the two dimensional confinement of electrons as lateral width of the conducting filament (CF) matches the fermi wavelength. The magnitude and number of the QC steps were found to increase from ∼2.5 to 12.5 and from 5 to 18, respectively by increasing the compliance current (IC) from 50 to 800µA which also increased the diameter of the CF from ∼1.2 to 3.3 nm. The enhancement in both number and magnitude of QC states was explained using electrochemical dissolution mechanism of CF of varying diameter. A thicker CF, formed at higherIC, undergoes a gradual rupture during reset process yielding a greater number of QC steps compared to a thinner CF. The realisation of QC states in the crossbar Cu/TiO2/Pt device as well asICmediated tunability of their magnitude and number may find applications in high-density resistive memory storage devices and neuromorphic computing.

Graphene materials in pollution trace detection and environmental improvement.

Water scarcity is a pressing issue experienced in numerous countries and is expected to become increasingly critical in the future. Anthropogenic activities such as mining, agriculture, industries, and domestic waste discharge toxic contaminants into natural water bodies, causing pollution. Addressing these environmental crises requires tackling the challenge of removing pollutants from water. Graphene oxide (GO), a form of graphene functionalized with oxygen-containing chemical groups, has recently garnered renewed interest due to its exceptional properties. These properties include a large surface area, mechanical stability, and adjustable electrical and optical characteristics. Additionally, surface functional groups like hydroxyl, epoxy, and carboxyl groups make GO an outstanding candidate for interacting with other materials or molecules. Because of its expanded structural diversity and enhanced overall properties, GO and its composites hold significant promise for a wide range of applications in energy storage, conversion, and environmental protection. These applications encompass hydrogen storage materials, photocatalysts for water splitting, the removal of air pollutants, and water purification. Serving as electrode materials for various lithium batteries and supercapacitors. Graphene-based materials, including graphene, graphene oxide, reduced graphene oxide, graphene polymer nanocomposites, and graphene nanoparticle metal hybrids, have emerged as valuable tools in energy and environmental remediation technologies. This review article provides an overview of the significant impact of graphene-based materials in various areas. Regarding energy-related topics, this article explores the applications of graphene-based materials in supercapacitors, lithium-ion batteries, and catalysts for fuel cells. Additionally, the article investigates recent advancements in detecting and treating persistent organic pollutants (POPs) and heavy metals using nanomaterials. The article also discusses recent developments in creating innovative nanomaterials, nanostructures, and treatment methods for addressing POPs and heavy metals in water. It aims to present the field's current state and will be a valuable resource for individuals interested in nanomaterials and related materials.

Patient-reported migraine-specific quality of life, activity impairment and headache impact with once-daily atogepant for preventive treatment of migraine in a randomized, 52-week trial.

BACKGROUND: Atogepant is an oral, small-molecule, calcitonin gene-related peptide receptor antagonist for the preventive treatment of episodic migraine. METHODS: In this 52-week, multicenter, randomized, open-label trial, adults with 4-14 monthly migraine days received atogepant 60 mg once-daily or standard care. Health outcome endpoints collected from participants randomized to atogepant included change from baseline in Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ v2.1) Role Function-Restrictive (RFR), Role Function-Preventive (RFP) and Emotional Function (EF) domain scores, change in Activity Impairment in Migraine-Diary (AIM-D) Performance of Daily Activities (PDA) and Physical Impairment (PI) domain scores, and change in Headache Impact Test-6 (HIT-6) total score. RESULTS: Of 744 randomized participants, 521 received atogepant 60 mg in the modified intent-to-treat population. Least-squares mean changes from baseline in MSQ-RFR score were 30.02 (95% confidence interval = 28.16-31.87) at week 12 and 34.70 (95% confidence interval = 32.74-36.66) at week 52. Improvements were also observed in other MSQ domains, AIM-D PDA, PI and HIT-6 total scores. A ≥5-point improvement from baseline in HIT-6 score was observed in 59.9% of participants at week 4 and 80.8% of participants at week 52. CONCLUSION: Over 52 weeks, atogepant 60 mg once-daily was associated with sustained improvements in quality of life and reductions in activity impairment and headache impact.Trial Registration: NCT03700320.

Harassment in the headache field: a global web-based cross-sectional survey.

BACKGROUND: Matters of workplace harassment are an important issue. This issue needs to be recognized and studied to prevent occurrences. These important sensitive areas of effective workplace management are increasingly gaining more interest. We aimed to identify the prevalence of workplace sexual, verbal and physical harassment among headache professionals. METHODS: We adopted a cross­sectional exploratory survey approach with quantitative design. The survey was distributed electronically among headache healthcare and research professionals globally through the International Headache Society (IHS). RESULTS: Data were obtained from 579 respondents (55.3%; 320/579 women). A large percentage of respondents (46.6%; 270/579) had experienced harassment; specifically, 16.1% (93/578) reported sexual harassment, 40.4% (234/579) verbal harassment and 5.5% (32/579) physical harassment. Women were almost seven times more likely to experience sexual harassment compared to men (odds ratio = 6.8; 95% confidence interval = 3.5-13.2). Although women did also more frequently report other types of harassment, this was not statistically significant (odds ratio = 1.4; 95% confidence interval = 1.0-2.0). CONCLUSIONS: Lifetime exposure to workplace harassment is prevalent among headache professionals, especially in women. The present study uncovers a widespread issue and calls for strategies to be implemented for building a healthy and safe workplace environment.

A qualitative evidence synthesis of patient perspectives on migraine treatment features and outcomes.

OBJECTIVES: We aimed to identify migraine treatment features preferred by patients and treatment outcomes most valued by patients. BACKGROUND: The values and preferences of people living with migraine are critical for both the choice of acute therapy and management approach of migraine. METHODS: We conducted a qualitative evidence synthesis. Two reviewers independently selected studies, appraised methodological quality, and undertook a framework synthesis. We developed summary of findings tables following the approach of Grading of Recommendations, Assessment, Development and Evaluations Confidence in the Evidence from Reviews of Qualitative Research to assess confidence in the findings. RESULTS: Of 1691 candidate references, we included 19 studies (21 publications) involving 459 patients. The studies mostly recruited White women from North America (11 studies) and Europe (8 studies). We identified eight themes encompassing features preferred by patients in a migraine treatment process. Themes described a treatment process that included shared decision-making, a tailored approach, trust in health-care professionals, sharing of knowledge and diversity of treatment options, a holistic approach that does not just address the headache, ease of communication especially for complex treatments, a non-undermining approach, and reciprocity with mutual respect between patient and provider. In terms of the treatment itself, seven themes emerged including patients' preferences for nonpharmacologic treatment, high effectiveness, rapidity of action, long-lasting effect, lower cost and more accessibility, self-management/self-delivery option that increases autonomy, and a mixed preference for abortive versus prophylactic treatments. The treatment outcomes that have high value to patients included maintaining or improving function; avoiding side effects, potential for addiction to medications, and pain reoccurrence; and avoiding non-headache symptoms such as nausea, vomiting, and sensitivity to light or sounds. CONCLUSION: Patient values and preferences were individually constructed, varied widely, and could be at odds with conventional medical perspectives and evidence of treatment effects. Considering the availability of numerous treatments for acute migraine, it is necessary that decision-making incorporates patient values and preferences identified in qualitative research. The findings of this qualitative synthesis can be used to facilitate an individually tailored approach, strengthen the patient-health-care system relationship, and guide choices and decisions in the context of a clinical encounter or a clinical practice guideline.

Post hoc analysis of clinical trial data and pharmacokinetic data to assess wearing-off of erenumab within monthly treatment cycle.

BACKGROUND: Treatment wearing-off has been reported for calcitonin gene-related peptide-pathway monoclonal antibodies, including erenumab, specifically in the last week of the monthly dosing cycle. OBJECTIVE: We sought to determine the consistency of erenumab effect throughout the monthly treatment cycle. METHODS: In this post hoc analysis of four pivotal double-blind, randomized controlled studies of erenumab in episodic and chronic migraine, we assessed wearing-off based on change in weekly migraine days at week 4 versus average over weeks 1-3 in each monthly dosing cycle. Analyses were conducted at each monthly dosing cycle in all patients, in responders (≥50% reduction in weekly migraine days), and in consistent responders (response in ≥2monthly cycles). RESULTS: There was no evidence of wearing-off in the full study populations of two global studies (N = 946 and N = 656) and two Japan studies (N = 475 and N = 261). In the full study population, mean change in weekly migraine days at week 4 compared with the average over week 1-3 ranged from 0.15 days improvement to 0.19 days worsening in the placebo group and 0.08 days improvement to 0.20 days worsening in the erenumab groups. A subgroup of responders experienced wearing-off, but the extent of wearing-off did not differ between erenumab and placebo groups. The mean change in weekly migraine days at week 4 compared with the average over weeks 1-3 ranged from 0.34 to 0.61 days worsening in the placebo group and 0.27 to 0.78 days worsening in the erenumab groups. Few patients had persistent wearing-off in ≥2 consecutive monthly treatment cycles. For erenumab-treated responders, serum erenumab concentrations were similar among patients experiencing wearing-off and those maintaining response. CONCLUSION: No systematic wearing-off with erenumab was identified. Further research is needed to determine if wearing-off reported for some patients in clinical practice reflects a true treatment response pattern or normal fluctuations in migraine frequency.

Health-related quality of life (hrQoL) among patients with primary cicatricial alopecia (PCA): A systematic review.

Cicatricial alopecia may lead to an enormous emotional burden, social distress, and psychological impairment affecting the quality of life. The objective of this review is to systematically describe the health-related quality of life in adults with primary cicatricial alopecia and its subtypes. Studies that (i) reported quality of life in patients with primary cicatricial alopecia or its subtypes; (ii) were original research and not a conference abstract or review (iii) with patients >18 years of age were included in the review. The studies not mentioning quality of life specifically for the cicatricial alopecia cohort were excluded. We searched for literature via OVID in Medline and Embase, in Web of Science, CINAHL, EBSCO (APA PsycArticles, APA PsycInfo, and PSYNDEX Literature), in the Cochrane Library and for grey literature from its inception date till 12 November 2022. The risk of bias was assessed by using the AXIS tool for cross-sectional studies by two independent authors. Thirteen observational cross-sectional and one single-arm study, including 572 patients and eight different instruments, fulfilled the inclusion criteria. Results are descriptively synthesized, and associated factors of quality of life are presented. The data from studies that used the Dermatology Life Quality Index tool (DLQI) showed that more than 70% of the patients have an impaired life quality. While trichodynia and anxiety have a negative effect on the quality of life, disease duration, education, employment, and marital status have no effect. The findings were inconsistent for other factors. Most of these studies failed to justify the sample size. Furthermore, the risk of bias assessment could not surely rule out a non-response bias. Our results suggest that cicatricial alopecia treatments must be integrated with psychosocial intervention and indicate the need for further research with homogenous and more comprehensive tools to identify and address this patient population's unmet mental health needs.

Quality of life in children and adolescents with alopecia areata-A systematic review.

Alopecia areata (AA) is an autoimmune-mediated non-scarring hair loss whose stigmatizing effect may have a severe psychosocial impact. AA has been reported to be correlated with bullying, reduced quality of life (QoL) and psychiatric comorbidities. The effect of AA on QoL in adult patients has been systematically reviewed and found to be detrimental. No systematic evaluation of QoL in children with AA has been performed. The aim of this review is to systematically describe QoL in the child and adolescent population affected by AA. A systematic review of multiple databases and grey literature sources was conducted. Search terms included, but were not limited to, alopecia areata and quality of life. Only studies reporting results on health-related QoL in children and adolescents were included. We evaluated the studies regarding the risk of bias, and conceptual rigour concerning the quality of life and performed a descriptive synthesis of findings. Eight studies met the inclusion criteria, encompassing 358 participants with AA and 64 healthy peers. Seven studies were quantitative using four different standardized questionnaires and scores to measure QoL. One study used a qualitative design. All studies described impairment of children and adolescents' QoL by AA. The most consistently affected QoL domain was embarrassment and self-consciousness. Further psychosocial implications of AA included bullying and limiting participation in school or spare time activities. Existing evidence indicates a substantial impact of AA on QoL in children. In daily clinical practice as well as for developing new treatments QoL in paediatric AA plays a critical role. It should be considered a key outcome in clinical research and decision-making.

Curcumin and PCI-34051 combined treatment ameliorates inflammation and fibrosis by affecting MAP kinase pathway.

OBJECTIVE: Bronchoconstriction, along with inflammation and hyperresponsiveness is the characteristic feature associated with asthma, contributing to variable airflow obstruction, which manifests shortness of breath, cough and wheeze, etc. Histone deacetylases 8 (HDAC8) is the member of class I HDAC family and known to regulate microtubule integrity and muscle contraction. Therefore, we aimed to investigate the effects of HDAC8 inhibition in murine model of asthma using Pan-HDAC inhibitor curcumin (CUR) and HDAC8-specific inhibitor PCI-34051 (PCI), alone and in combination. MATERIALS AND METHODS: To develop asthmatic mouse model, Balb/c mice were sensitized and challenged with ovalbumin (OVA). CUR (10 mg/kg, pre, post, alone and combined treatment) and PCI (0.5 mg/kg), were administered through intranasal (i.n) route, an hour before OVA aerosol challenge. Effects of HDAC8 inhibition by CUR and PCI pretreatments were evaluated in terms of inflammation, oxidative stress and fibrosis markers. Efficacy of curcumin post-treatment (CUR(p)) was also evaluated simultaneously. RESULTS: Inflammatory cell recruitment, oxidative stress (reactive oxygen species, nitric oxide), histamine and Immunoglobulin E (IgE) levels and expression of fibrosis markers including hydroxyproline, matrix metalloproteinases-9 and alpha smooth muscle actin (MMP-9 and α-SMA) were significantly reduced by CUR, CUR(p), PCI-alone and combined treatments. Protein expressions of HDAC8, Nuclear factor-κB (NF-κB) accompanied by MAPKs (mitogen-activated protein kinases) were significantly reduced by the treatments. Structural alterations were examined by histopathological analysis and linked with the fibrotic changes. CONCLUSIONS: Present study indicates protective effects of HDAC8 inhibition in asthma using HDAC8 using CUR and PCI alone or in combination, attenuates airway inflammation, fibrosis and remodeling; hence, bronchoconstriction was accompanied through modulation of MAP kinase pathway.

Migraine: integrated approaches to clinical management and emerging treatments.

Migraine is a highly disabling neurological disorder that directly affects more than 1 billion individuals worldwide. Available treatment options differ between countries and include acute, preventive, and non-pharmacological therapies. Because of major progress in the understanding of migraine pathogenesis, novel mechanism-based medications have emerged and expanded the armamentarium of treatments. We provide a comprehensive overview of the current standard of care that will enable informed clinical management. First, we discuss the efficacy, tolerability, and safety profile of various pharmacological therapies for acute and preventive treatment of migraine. Second, we review the current knowledge on non-pharmacological therapies, such as neuromodulation and biobehavioural approaches, which can be used for a multidisciplinary approach to clinical management. Third, we emphasise that any effective treatment strategy starts with building a therapeutic plan tailored to individual clinical characteristics, preferences, and needs. Finally, we explore the outlook of emerging mechanism-based treatments that could address unmet challenges in clinical management of migraine.

Sensing Host Health: Insights from Sensory Protein Signature of the Metagenome.

The human microbiota, which comprises an ensemble of taxonomically and functionally diverse but often mutually cooperating microorganisms, benefits its host by shaping the host immunity, energy harvesting, and digestion of complex carbohydrates as well as production of essential nutrients. Dysbiosis in the human microbiota, especially the gut microbiota, has been reported to be linked to several diseases and metabolic disorders. Recent studies have further indicated that tracking these dysbiotic variations could potentially be exploited as biomarkers of disease states. However, the human microbiota is not geography agnostic, and hence a taxonomy-based (microbiome) biomarker for disease diagnostics has certain limitations. In comparison, (microbiome) function-based biomarkers are expected to have a wider applicability. Given that (i) the host physiology undergoes certain changes in the course of a disease and (ii) host-associated microbial communities need to adapt to this changing microenvironment of their host, we hypothesized that signatures emanating from the abundance of bacterial proteins associated with the signal transduction system (herein referred to as sensory proteins [SPs]) might be able to distinguish between healthy and diseased states. To test this hypothesis, publicly available metagenomic data sets corresponding to three diverse health conditions, namely, colorectal cancer, type 2 diabetes mellitus, and schizophrenia, were analyzed. Results demonstrated that SP signatures (derived from host-associated metagenomic samples) indeed differentiated among healthy individual and patients suffering from diseases of various severities. Our finding was suggestive of the prospect of using SP signatures as early biomarkers for diagnosing the onset and progression of multiple diseases and metabolic disorders. IMPORTANCE The composition of the human microbiota, a collection of host-associated microbes, has been shown to differ among healthy and diseased individuals. Recent studies have investigated whether tracking these variations could be exploited for disease diagnostics. It has been noted that compared to microbial taxonomies, the ensemble of functional proteins encoded by microbial genes are less likely to be affected by changes in ethnicity and dietary preferences. These functions are expected to help the microbe adapt to changing environmental conditions. Thus, healthy individuals might harbor a different set of genes than diseased individuals. To test this hypothesis, we analyzed metagenomes from healthy and diseased individuals for signatures of a particular group of proteins called sensory proteins (SP), which enable the bacteria to sense and react to changes in their microenvironment. Results demonstrated that SP signatures indeed differentiate among healthy individuals and those suffering from diseases of various severities.

Protective effects of intranasal curcumin on silica-induced lung damage.

OBJECTIVE: Being anti-inflammatory and an antioxidant in nature, curcumin has been studied for its anti-asthmatic effects, but its impact on silicosis has not been investigated before. It is a form of occupational lung illness caused by inhaling crystalline silica. It is particularly common among those who work in construction-related sectors. Therefore, present study has been undertaken to investigate impact of intranasal curcumin on silica induced lung damage in mice model of silicosis. MATERIALS AND METHODS: Mice model of silicosis was developed by intranasal silica instillation (2.5 mg/mice) for different durations mainly 7, 14 and 21 days, where the longest duration of silica exposure (21 days) mimics chronic occupational exposure of silica dust leading to silicosis. Curcumin (5 mg/kg,i.n) and /or dexamethasone, a known corticosteroid (10 mg/kg,i.p) was administered an hour prior to silica administration. RESULTS: Present study revealed silica induced lung damage in the mice model of silicosis characterized by airway inflammation, collagen deposition and enhanced expression of fibrosis markers (MMP-9, α-SMA, Hydroxyproline), which were significantly reduced in curcumin treatment groups. Inhibitory effects of curcumin were compared with standard drug, dexamethasone, a corticosteroid and was found better in protecting structural alterations in the lung. Damaged and abnormal mitochondria (enlarged and irregular shapes) were observed in silicosis group which were reduced in curcumin and dexamethasone treatment groups as revealed in transmission electron microscopic studies. CONCLUSIONS: Present study shows protective effects of intranasal curcumin on silica-induced airway inflammation and structural changes thereby lung damage. Hence, it can be considered as an alternative and complementary medication for silicosis.

Intranasal curcumin and sodium butyrate modulates airway inflammation and fibrosis via HDAC inhibition in allergic asthma.

Asthma being an inflammatory disease of the airways lead to structural alterations in lungs which often results in the severity of the disease. Curcumin, diferuloylmethane, is well known for its medicinal properties but its anti-inflammatory potential via Histone deacetylase inhibition (HDACi) has not been revealed yet. Therefore, we have explored here, anti-inflammatory and anti-fibrotic potential of intranasal curcumin via HDAC inhibition and compared its potential with Sodium butyrate (SoB), a known histone deacetylase inhibitor of Class I and II series. Anti-inflammatory potential of SoB, has been investigated in cancer but not been studied in asthma before. MATERIALS AND METHODS: In present study, ovalbumin (OVA) was used to sensitize Balb/c mice and later exposed to (1%) OVA aerosol. Curcumin (5 mg/kg) and Sodium butyrate (50 mg/kg) was administered through intranasal route an hour before OVA aerosol challenge. Efficacies of SoB and Curcumin as HDAC inhibitors were evaluated in terms of different inflammatory parameters like, total inflammatory cell count, reactive oxygen species (ROS), histamine release, nitric oxide and serum IgE levels. Inflammatory cell recruitment was analyzed by H&E staining and structural alterations were revealed by Masson's Trichrome staining of lung sections. RESULTS: Enhanced Matrix Metalloproteinase-2 and 9 (MMP-2 and MMP-9) activities were observed in bronchoalveolar lavage fluid (BALF) of asthmatic mice by gelatin zymography which was inhibited in both treatment groups. Protein expressions of MMP-9, HDAC 1, H3acK9 and NF-kB p65 were modulated in intranasal curcumin and SoB pretreatment groups. CONCLUSION: This is the first report where intranasal curcumin inhibited asthma severity via affecting HDAC 1 (H3acK9) leading to NF-kB suppression in mouse model of allergic asthma.

Intranasal curcumin and dexamethasone combination ameliorates inflammasome (NLRP3) activation in lipopolysachharide exposed asthma exacerbations.

The inflammasome NOD-like receptor (NLR) family, the pyrin domain containing 3 (NLRP3) is closely associated with exacerbation of asthma as endotoxin (lipopolysaccharide, LPS) is one of its activators present in the environment. Present study is undertaken to investigate anti-inflammatory effects of a well known phytochemical, curcumin, which might regulate LPS exposed asthma exacerbations by modulating NLRP3 activation if given through intranasal route. Balb/c mice were sensitized with intraperitoneal injection of OVA (Ovalbumin; 100 µg of OVA with alum) from day 1 to 8 and exposed to LPS with 1% OVA aerosol from day 9 to 15. LPS (0.1 µg) was given an hour before sensitization and OVA-aerosol challenge. Significant decrease in inflammatory cell recruitment and restoration of structural changes in lungs, alterations in mRNA and protein expressions of TLR-4, NF-κB, NLRP3, Caspase-1, IL-1ß, MMP-9, IL-5 and IL-17 in intranasal curcumin alone and corticosteroid combined pretreatment group.

Perceived barriers to career progression in the headache field: A global web-based cross-sectional survey.

BACKGROUND: It is well recognized that underrepresented and minoritized groups do not have the same career opportunities. However, there are limited data on the range and specifics of potential barriers that withhold people in headache medicine and science from reaching their full potential. Moreover, people from different geographical regions often perceive different challenges. We aimed to identify world-wide perceived career barriers and possibilities for promoting equality amongst professionals in the headache fields. METHODS: A cross-sectional online survey was conducted among professionals in the field of headache globally. The questions of the survey were aimed at assessing perceived career barriers in four domains: professional recognition, opportunities in scientific societies, clinical practice, and salary and compensation. Perceived mentorship was also assessed. RESULTS: In total 580 responders completed the survey (55.3% women). Gender was the most important perceived barrier in almost all domains. Additionally, country of birth emerged as an important barrier to participation in international scientific societies. Career barriers varied across world regions. CONCLUSION: It is essential that longstanding and ongoing disparities by gender and country of origin for professionals in the headache field are globally acknowledged and addressed in areas of recruitment, retention, opportunities, mentor- and sponsorships, and advancement.

Acute Treatment of Headache (Focus on Migraine).

Acute treatments for migraine and cluster headache are necessary to abort attacks, relieve pain and associated symptoms, and restore an individual's ability to function. Acute headache treatments consist of a variety of medication and nonmedication options. In this article, we discuss the approach to acute treatment of migraine and cluster headache. We summarize the level of evidence to support each acute medication class according to recent systematic reviews and meta-analyses, as well as guideline recommendations from the American Headache Society, American Academy of Neurology, and European Federation of Neurological Society.

Th1-Th2 and M1-M2 interplay sculpt Aeromonas hydrophila pathogenesis in zebrafish (Danio rerio).

Aeromonas hydrophila is an important aquatic zoonotic pathogen that causes septicemia, necrotizing fasciitis and gastroenteritis in various aquatic and non-aquatic animals. However, the pathogenesis of A. hydrophila is not fully understood. Here, we examined the pathogenicity and histopathology of A. hydrophila in the zebrafish (Danio rerio) model system. We found that the intensity of symptoms and mortality is dose-dependent. Bacterial colonization studies demonstrated that A. hydrophila never cleared out from the fish body but stayed in a state of inactivity till it enters a fresh host. Reinfection studies showed that exposure to A. hydrophila provides immunity against future infection and hence improves fish survival. Gene expression studies revealed the crosstalk between T-helper cell and macrophage responses in fish immune system in response to A. hydrophila and infection memory. Histopathological studies showed that symptoms of tissue damage and inflammation lasted for less duration with less intensity in immunized fish when compared to non-immunized fish. Together, our results suggest that the zebrafish model is a useful system in studying the interplay between A. hydrophila pathogenesis, persistence and immunity.

Post-COVID Headache: A Literature Review.

PURPOSE OF REVIEW: Post-COVID headache may be unique in presentation and mechanism, often presenting as a new phenotype in patients with a history of a primary headache disorder or resulting in a new headache syndrome in those without history of headache. This review presents a description of the literature published focused on post-COVID headache. Additionally, we discuss potential mechanisms and considerations for treatment of post-COVID headache. RECENT FINDINGS: Headache is one of the most common symptoms of COVID. Common characteristics are revealed when reviewing the phenotypes of headaches that have been described in patients with COVID-19, with most headache phenotypes resembling migraine and new persistent daily headache. Post-COVID headaches are often described as moderate to severe, persistent, and treatment refractory. This review highlights the diversity of presentation of headaches that present as a complication of COVID-19. Treatment of post-COVID headache is challenging, especially in the setting of a pandemic where resources are limited. CLINICAL CASE: A 42-year-old woman with a history of episodic migraine without aura presents over video visit with a new headache type. Her typical headaches are predominantly left sided, throbbing in nature, and associated with photophobia and phonophobia. They are fully relieved by oral sumatriptan 2 h after treatment. She describes this new headache as a constant, pulsating, holocephalic pain with no other migrainous features that have been ongoing for 6 weeks. She notes that the headache has been persistent since that time. She has tried over-the-counter acetaminophen and ibuprofen and her typical migraine abortive therapy without relief. She is debilitated and wonders if there is anything that will take the pain away. She shares that she tested positive for COVID-19 about 2 days prior to headache onset and has associated rhinorrhea, anosmia, and ageusia.

MetagenoNets: comprehensive inference and meta-insights for microbial correlation networks.

Microbial association networks are frequently used for understanding and comparing community dynamics from microbiome datasets. Inferring microbial correlations for such networks and obtaining meaningful biological insights, however, requires a lengthy data management workflow, choice of appropriate methods, statistical computations, followed by a different pipeline for suitably visualizing, reporting and comparing the associations. The complexity is further increased with the added dimension of multi-group 'meta-data' and 'inter-omic' functional profiles that are often associated with microbiome studies. This not only necessitates the need for categorical networks, but also integrated and bi-partite networks. Multiple options of network inference algorithms further add to the efforts required for performing correlation-based microbiome interaction studies. We present MetagenoNets, a web-based application, which accepts multi-environment microbial abundance as well as functional profiles, intelligently segregates 'continuous and categorical' meta-data and allows inference as well as visualization of categorical, integrated (inter-omic) and bi-partite networks. Modular structure of MetagenoNets ensures logical flow of analysis (inference, integration, exploration and comparison) in an intuitive and interactive personalized dashboard driven framework. Dynamic choice of filtration, normalization, data transformation and correlation algorithms ensures, that end-users get a one-stop solution for microbial network analysis. MetagenoNets is freely available at https://web.rniapps.net/metagenonets.