Advocacy Connection Team-Now educational program for headache fellows and patients/caregivers: Assessment of educational objectives.

OBJECTIVE: To assess for improvement in comfort in participating in advocacy for migraine and headache disorders and knowledge needed for successful advocacy. BACKGROUND: The Advocacy Connection Team (ACT)-Now program is an educational program offered through Miles for Migraine, a non-profit advocacy organization. It is designed to teach headache fellows and patients advocacy skills. METHODS: In a cross-sectional pre-test-post-test design, the 2021 ACT-Now cohort of 98 participants were administered a set of 11 pre-course survey questions identifying their role (healthcare provider/headache fellow or patient/caregiver), baseline knowledge of migraine-related disability and stigma, and baseline engagement and comfort with advocating. The post-course survey questions were the same as the pre-course questions, with the addition of one question assessing knowledge of migraine-related disability, additional questions addressing comfort levels advocating with insurance and policymakers, as well as creating an advocacy plan. RESULTS: For the pre-course survey, 69 participants responded and for the post-course survey, 40 participants responded. Compared to the pre-course survey, participants were able to correctly identify epidemiological data about migraine following the ACT-Now course (pre-course 46% correct, post-course 58% correct, p = 0.263). There was also an increase in the comfort level of participants in advocacy activities, including the creation of an advocacy action plan (pre-course 23% were "very comfortable" advocating, post-course 63%, p < 0.05). CONCLUSION: These results demonstrate that ACT-Now is effective at improving advocacy skills in a mixed cohort of patients and headache fellows, giving them the skills to create advocacy plans and engage with other patients and physicians, payers, and policymakers to create a more understanding, equitable and compassionate world for persons with migraine and other headache diseases.

Unique Considerations in Episodic Migraine: Underserved Populations.

PURPOSE OF REVIEW: Episodic migraine is a common and disabling neurological disorder that is underdiagnosed and undertreated. Additional barriers are put in place for those who belong to an underserved population. This could be based on race, ethnicity, gender, sexual orientation, or socioeconomic status. RECENT FINDINGS: There has been a lot of interest in understanding the extent of these disparities, but studies for many of these groups are lacking. More work is needed to understand the disparities and needs of underserved populations. Most of the literature has been done for Black populations but there are many other underserved communities that need assessment and intervention. The healthcare community needs to take action to improve support for populations with a higher incidence of migraine and disability, yet a lower rate of diagnosis and treatment. Some recommendations include awareness of biases, systemic changes, education, and including diverse populations in research and training.

Role of Rehabilitation in Opioid Tapering: A Scoping Review.

Purpose: Among industrialized countries, Canada has the second-highest opioid prescribing rate for pain management. Physiotherapy and occupational therapy interventions are potential non-pharmacological alternatives. We undertook a scoping review to explore and summarize the current evidence describing the interventions included or used in physiotherapy and occupational therapy in opioid tapering for individuals with chronic pain. Method: A systematic search of the peer-reviewed health databases was conducted, with data synthesis guided by Arksey and O'Malley's scoping review methodology. Articles were included in the narrative synthesis if (1) interventions within the scope of practice for physiotherapists or occupational therapists were described or these professionals were part of interdisciplinary care and (2) opioid tapering or reduction was addressed. Results: The 39 articles identified included 2 systematic reviews, 9 narrative reviews or commentaries, 2 case reports, 11 uncontrolled cohort studies, 1 cross-sectional study, 5 randomized controlled trials, 4 programme evaluations, and 4 qualitative studies. Of the 28 studies reporting specific outcomes, 25 reported positive outcomes of rehabilitation interventions for opioid tapering. There was greater representation of interventions from physiotherapy than from occupational therapy: few articles contained substantive descriptions (e.g., dosage and duration). Conclusions: The evidence to guide therapists in supporting opioid tapering for people with chronic pain seems to be limited. Further research is needed to establish effectiveness for stand-alone interventions and as part of a comprehensive rehabilitation approach.

Objectif : dans les pays industrialisés, le Canada présente le deuxième taux de prescriptions d'opioïdes en importance pour la gestion de la douleur. Les interventions en physiothérapie et en ergothérapie font partie des solutions non pharmacologiques possibles pour remplacer ces médicaments. Les chercheurs ont entrepris une étude exploratoire pour étudier et résumer les données probantes à jour qui décrivent les interventions incluses ou utilisées en physiothérapie et en ergothérapie pour mettre graduellement un terme à l'utilisation d'opioïdes chez les personnes souffrant de douleur chronique. Méthodologie : les chercheurs ont réalisé une recherche systématique des bases de données sur la santé dotées d'un comité d'évaluation et ont fait reposer la synthèse des données sur la méthodologie exploratoire d'Arksey et O'Malley. Les articles étaient intégrés à la synthèse narrative si 1) des interventions se situant dans le champ de pratique des physiothérapeutes et des ergothérapeutes y étaient décrites ou si ces professionnels faisaient partie des soins interdisciplinaires et 2) l'arrêt graduel ou la réduction des opioïdes y était abordé. Résultats : les 39 articles retenus incluaient deux analyses systématiques, neuf études ou commentaires narratifs, deux rapports de cas, 11 études de cohorte non contrôlées, une étude transversale, cinq essais aléatoires et contrôlés, quatre évaluations de programme et quatre études qualitatives. Des 28 études décrivant des résultats précis, 25 incluaient les résultats d'interventions de réadaptation qui contribuaient à l'arrêt graduel de la prise d'opioïdes. Il y avait plus d'interventions en physiothérapie qu'en ergothérapie : peu d'articles contenaient des descriptions plus détaillées (p. ex., dosage et durée). Conclusion : les données probantes semblent limitées pour orienter les thérapeutes afin qu'ils contribuent à l'arrêt graduel des opioïdes chez les personnes atteintes de maladie chronique. D'autres recherches s'imposent pour établir l'efficacité des interventions autonomes, dans le cadre d'une approche de réadaptation complète.

Call to Action: Maternal Health and Saving Mothers: A Policy Statement From the American Heart Association.

The United States has the highest maternal mortality rates among developed countries, and cardiovascular disease is the leading cause. Therefore, the American Heart Association has a unique role in advocating for efforts to improve maternal health and to enhance access to and delivery of care before, during, and after pregnancy. Several initiatives have shaped the time course of major milestones in advancing maternal and reproductive health equity in the United States. There have been significant strides in improving the timeliness of data reporting in maternal mortality surveillance and epidemiological programs in maternal and child health, yet more policy reforms are necessary. To make a sustainable and systemic impact on maternal health, further efforts are necessary at the societal, institutional, stakeholder, and regulatory levels to address the racial and ethnic disparities in maternal health, to effectively reduce inequities in care, and to mitigate maternal morbidity and mortality. In alignment with American Heart Association's mission "to be a relentless force for longer, healthier lives," this policy statement outlines the inequities that influence disparities in maternal outcomes and current policy approaches to improving maternal health and suggests additional potentially impactful actions to improve maternal outcomes and ultimately save mothers' lives.

An Educational Workshop to Improve Neurology Resident Understanding of Burnout, Substance Abuse, and Mood Disorders.

Introduction: Burnout, substance abuse, and mood disorders are prevalent among neurology residents. Increased recognition of concerning behaviors might encourage more access to mental health resources and reduce burnout. Methods: We created an educational resource reviewing burnout, substance abuse, and mood disorders for neurology residents. This resource included an online module (control) and a role-play scenario offered only to one cohort (intervention). Online surveys assessed knowledge as well as confidence in the ability to recognize concerning behaviors. A practical assessment using a previously published "Stressed Resident" video was also conducted among resident cohorts. Results: Of neurology residents, 18 participated in the activity, with nine in the control group and nine in the intervention group. In the postvideo survey, the residents who participated in a role-play activity outperformed a control cohort of their peers when identifying signs of burnout, mood disorders, and substance abuse portrayed in the video (84% vs. 72%; t test, p = .01). Residents indicated increased confidence in the ability to recognize symptoms of maladaptive stress as well as identify resources for themselves and peers. Participants demonstrated no difference in knowledge-based questions scores on pre- and postactivity assessments. Discussion: Our educational resource improved resident ability to recognize signs of maladaptive stress and to identify residents that are a risk to patient safety. The activity is easy to implement and can be easily adapted outside neurology. Limited sample sizes may limit the ability to demonstrate this tool's impact on knowledge of burnout, substance abuse, and mood disorders.

Nonprofit Advocacy at the American Heart Association: Creating a Visionary Way Forward at Our 40th Anniversary: An American Heart Association Policy Statement.

In 2021, the American Heart Association celebrates its 40th anniversary in advocacy. This policy statement details the arc of the organization's nonpartisan, evidence-based, equity-focused approach to advocating for public policy change, highlighting key milestones and describing the core components of the association's capacity and activity at all levels of government. This policy statement presents a vision and strategic imperative for future American Heart Association advocacy efforts to inform and influence policy changes that advance equitable, impactful societal solutions that transform and improve cardiovascular health for everyone. The American Heart Association maintains accountability by measuring and evaluating the totality of this work and its impact on equitable health outcomes. The American Heart Association will apply these lessons to constantly refine its own strategic policy focus and advocacy efforts. The association will also serve as a resource and catalyst to other organizations working to engage and educate policy makers, partners, the media, and funders about the important role and contribution of public policy change to achieve shared goals.

Calcitonin Gene-Related Peptide Antagonists in the Treatment of Episodic Migraine.

Migraine is a prevalent, disabling neurological disorder involving the trigeminovascular system. Previous treatments were either originally intended for other conditions and/or associated with intolerable adverse effects (AEs). Calcitonin gene-related peptide (CGRP) is the most prevalent neuropeptide in the trigeminal afferent neurons and plays a significant role in pain sensitization central to migraine. The CGRP antagonists (gepants and monoclonal antibodies) are the first treatments created specifically for migraine, modulating pain signaling pathways and alleviating migraine attacks and recurrences. With their efficacy in several clinical trials and relatively fewer AEs, the CGRP antagonists show great promise for use in episodic migraine.

Engaging the Community through Science Nights: An Elementary School Case Study.

Parental involvement increases K-12 student interest in STEM careers; however, when parents lack confidence in STEM content, or language and cultural barriers exist, parental engagement decreases. The Teacher Enrichment Initiatives (TEI) collects annual teacher feedback regarding the level of parental involvement with students during science nights, which laid the foundation for teachers to develop a science night training. Using qualitative methods, this single-case study follows elementary teachers who participated in the TEI science night training as they implement a Science Night program at a majority-minority elementary school. Data were gathered by TEI staff during the inaugural and third year of the Science Night program showing an increase in attendance from 700 (2016) to 800 (2018) and an increase in parental engagement with their student in STEM-related activities from 46% (2016) to 62% (2018). The data and follow-up summary were used by the case study school teachers to write and secure grants to support an annual Science Night program. This case study suggests Science Nights can be a mechanism to promote parental engagement with their student in hands-on STEM activities. Further, this case study suggests teacher feedback and inclusion in developing a science night model is central to successful implementation of a science night program.

Mini-G proteins: Novel tools for studying GPCRs in their active conformation.

Mini-G proteins are the engineered GTPase domains of Gα subunits. They couple to GPCRs and recapitulate the increase in agonist affinity observed upon coupling of a native heterotrimeric G protein. Given the small size and stability of mini-G proteins, and their ease of expression and purification, they are ideal for biophysical studies of GPCRs in their fully active state. The first mini-G protein developed was mini-Gs. Here we extend the family of mini-G proteins to include mini-Golf, mini-Gi1, mini-Go1 and the chimeras mini-Gs/q and mini-Gs/i. The mini-G proteins were shown to couple to relevant GPCRs and to form stable complexes with purified receptors that could be purified by size exclusion chromatography. Agonist-bound GPCRs coupled to a mini-G protein showed higher thermal stability compared to the agonist-bound receptor alone. Fusion of GFP at the N-terminus of mini-G proteins allowed receptor coupling to be monitored by fluorescence-detection size exclusion chromatography (FSEC) and, in a separate assay, the affinity of mini-G protein binding to detergent-solubilised receptors was determined. This work provides the foundation for the development of any mini-G protein and, ultimately, for the structure determination of GPCRs in a fully active state.

Structure and dynamics of a constitutively active neurotensin receptor.

Many G protein-coupled receptors show constitutive activity, resulting in the production of a second messenger in the absence of an agonist; and naturally occurring constitutively active mutations in receptors have been implicated in diseases. To gain insight into mechanistic aspects of constitutive activity, we report here the 3.3 Å crystal structure of a constitutively active, agonist-bound neurotensin receptor (NTSR1) and molecular dynamics simulations of agonist-occupied and ligand-free receptor. Comparison with the structure of a NTSR1 variant that has little constitutive activity reveals uncoupling of the ligand-binding domain from conserved connector residues, that effect conformational changes during GPCR activation. Furthermore, molecular dynamics simulations show strong contacts between connector residue side chains and increased flexibility at the intracellular receptor face as features that coincide with robust signalling in cells. The loss of correlation between the binding pocket and conserved connector residues, combined with altered receptor dynamics, possibly explains the reduced neurotensin efficacy in the constitutively active NTSR1 and a facilitated initial engagement with G protein in the absence of agonist.

Acute adverse events associated with ventral slot decompression in 546 dogs with cervical intervertebral disc disease.

OBJECTIVE: To report the frequency, types, and risk factors for acute perioperative adverse events (AEs) in dogs that had ventral slot decompression (VSD) for cervical intervertebral disc disease (IVDD). DESIGN: Retrospective, case-control study. ANIMALS: Dogs (n = 546) with cervical IVDD treated by VSD; 54 cases experiencing AE and 492 controls. METHODS: Historical, clinical, diagnostic, operative, and outcome data were collected. AE were graded using a Spine Adverse Events Severity (SAVES) system. Associations between the development of AE and hypothesized risk factors were analyzed using bi- and multi-variable analyses. RESULTS: AE were observed in 54 dogs (9.9%). Minor AE (SAVES Grade 1-2) occurred in 3.5% (19 dogs) and major (SAVES Grades 3-5) AE in 6.4% (35 dogs). Deterioration in neurologic status (n = 13), persistent pain (12), and intraoperative hemorrhage (7) were common major AE. NSAID administration, surgeon experience, C7-T1 disc location, and intraoperative hypotension were significantly associated with AE in multivariate analyses. Improvement of AE occurred in 48/54 (88.9%) of cases, although reoperative neurosurgery was required in 48.5% (17/35) of dogs experiencing major AE. Dogs with major AE had significantly longer hospitalization and worse outcomes than dogs with minor AE or controls. No fatal AE occurred, although 0.7% (4/546) of dogs were euthanatized postoperatively. CONCLUSIONS: AE occurred in 9.9% of dogs that had VSD, and were significantly associated with perioperative hypotension, C7-T1 disc extrusions, surgeon experience, and NSAID usage. Identification of a major postoperative AE is an indication for immediate diagnostic imaging studies, as 50% of dogs experiencing major AE required reoperation.

MreB: pilot or passenger of cell wall synthesis?

The discovery that the bacterial cell shape determinant MreB is related to actin spurred new insights into bacterial morphogenesis and development. The trafficking and mechanical roles of the eukaryotic cytoskeleton were hypothesized to have a functional ancestor in MreB based on evidence implicating MreB as an organizer of cell wall synthesis. Genetic, biochemical and cytological studies implicate MreB as a coordinator of a large multi-protein peptidoglycan (PG) synthesizing holoenzyme. Recent advances in microscopy and new biochemical evidence, however, suggest that MreB may function differently than previously envisioned. This review summarizes our evolving knowledge of MreB and attempts to refine the generalized model of the proteins organizing PG synthesis in bacteria. This is generally thought to be conserved among eubacteria and the majority of the discussion will focus on studies from a few well-studied model organisms.

Positioning cell wall synthetic complexes by the bacterial morphogenetic proteins MreB and MreD.

In Caulobacter crescentus, intact cables of the actin homologue, MreB, are required for the proper spatial positioning of MurG which catalyses the final step in peptidoglycan precursor synthesis. Similarly, in the periplasm, MreC controls the spatial orientation of the penicillin binding proteins and a lytic transglycosylase. We have now found that MreB cables are required for the organization of several other cytosolic murein biosynthetic enzymes such as MraY, MurB, MurC, MurE and MurF. We also show these proteins adopt a subcellular pattern of localization comparable to MurG, suggesting the existence of cytoskeletal-dependent interactions. Through extensive two-hybrid analyses, we have now generated a comprehensive interaction map of components of the bacterial morphogenetic complex. In the cytosol, this complex contains both murein biosynthetic enzymes and morphogenetic proteins, including RodA, RodZ and MreD. We show that the integral membrane protein, MreD, is essential for lateral peptidoglycan synthesis, interacts with the precursor synthesizing enzymes MurG and MraY, and additionally, determines MreB localization. Our results suggest that the interdependent localization of MreB and MreD functions to spatially organize a complex of peptidoglycan precursor synthesis proteins, which is required for propagation of a uniform cell shape and catalytically efficient peptidoglycan synthesis.

The cell shape proteins MreB and MreC control cell morphogenesis by positioning cell wall synthetic complexes.

MreB, the bacterial actin homologue, is thought to function in spatially co-ordinating cell morphogenesis in conjunction with MreC, a protein that wraps around the outside of the cell within the periplasmic space. In Caulobacter crescentus, MreC physically associates with penicillin-binding proteins (PBPs) which catalyse the insertion of intracellularly synthesized precursors into the peptidoglycan cell wall. Here we show that MreC is required for the spatial organization of components of the peptidoglycan-synthesizing holoenzyme in the periplasm and MreB directs the localization of a peptidoglycan precursor synthesis protein in the cytosol. Additionally, fluorescent vancomycin (Van-FL) labelling revealed that the bacterial cytoskeletal proteins MreB and FtsZ, as well as MreC and RodA, were required for peptidoglycan synthetic activity. MreB and FtsZ were found to be required for morphogenesis of the polar stalk. FtsZ was required for a cell cycle-regulated burst of peptidoglycan synthesis early in the cell cycle resulting in the synthesis of cross-band structures, whereas MreB was required for lengthening of the stalk. Thus, the bacterial cytoskeleton and cell shape-determining proteins such as MreC, function in concert to orchestrate the localization of cell wall synthetic complexes resulting in spatially co-ordinated and efficient peptidoglycan synthetic activity.