Care Gaps and Recommendations in Vestibular Migraine: An Expert Panel Summit

Vestibular migraine (VM) is an increasingly recognized pathology yet remains as an underdiagnosed cause of vestibular disorders. While current diagnostic criteria are codified in the 2012 Barany Society document and included in the third edition of the international classification of headache disorders, the pathophysiology of this disorder is still elusive. The Association for Migraine Disorders hosted a multidisciplinary, international expert workshop in October 2020 and identified seven current care gaps that the scientific community needs to resolve, including a better understanding of the range of symptoms and phenotypes of VM, the lack of a diagnostic marker, a better understanding of pathophysiologic mechanisms, as well as the lack of clear recommendations for interventions (nonpharmacologic and pharmacologic) and finally, the need for specific outcome measures that will guide clinicians as well as research into the efficacy of interventions. The expert group issued several recommendations to address those areas including establishing a global VM registry, creating an improved diagnostic algorithm using available vestibular tests as well as others that are in development, conducting appropriate trials of high quality to validate current clinically available treatment and fostering collaborative efforts to elucidate the pathophysiologic mechanisms underlying VM, specifically the role of the trigemino-vascular pathways.

Evaluation of Sports-Related Concussion in Children (5–12) and Adolescents (13–18)

ObjectiveThe objective of this study was to examine the association between sport/non-sport concussions as well as age and time to recovery after concussion diagnosis in children and adolescents.BackgroundThere is an ongoing debate between policy makers and medical specialists on when is the appropriate time to allow children to begin playing contact sports. This dilemma is important because sports are incredibly prevalent in our child and adolescent population today. There is still significant debate if age at time of concussion diagnosis is associated with long term affects and time to recovery.Design/MethodsOf the 725 patients who received a diagnosis of concussion at Children's of Alabama (COA) from 2018 to 2019, 350 patients were included for retrospective cohort review based on documented recovery data defined as follow up appointment PRN (as needed) or begin return to play protocol. 221 patients were lost to follow up while 7 were excluded for concomitant skull fracture. Recovery time, patient demographic data, symptoms severity score, and injury characteristics were then analyzed for each patient.ResultsOverall, the mean time of recovery after new diagnosis of any concussion was 87.2 days. The mean time to documented recovery in sports-related concussion was 82.6 days compared to 98.5 days in non-sports related concussion. Of note, both the 5–12 and 13–18 age groups had the same mean time to recovery at 87 days.ConclusionsSports related concussion showed decreased mean time to recovery compared to non-sports related concussion. Also, age did not play a factor in time to recovery as there was no difference in the 2 age groups. This data, along with the NCAA-DOD Care Consortium showing repetitive head injury during early adolescence is unrelated to brain health as measured by specific outcome measures, has the potential to provide valuable information for future policy on child and adolescent sports.

A Framework for Reviewing Silvopastoralism: A New Zealand Hill Country Case Study

Silvopastoral systems can be innovative solutions to agricultural environmental degradation, especially in hilly and mountainous regions. A framework that expresses the holistic nature of silvopastoral systems is required so research directions can be unbiased and informed. This paper presents a novel framework that relates the full range of known silvopastoral outcomes to bio-physical tree attributes, and uses it to generate research priorities for a New Zealand hill country case study. Current research is reviewed and compared for poplar (Populus spp.), the most commonly planted silvopastoral tree in New Zealand hill country, and kānuka (Kunzea spp.), a novel and potentially promising native alternative. The framework highlights the many potential benefits of kānuka, many of which are underappreciated hill country silvopastoral outcomes, and draws attention to the specific outcome research gaps for poplar, despite their widespread use. The framework provides a formalised tool for reviewing and generating research priorities for silvopastoral trees, and provides a clear example of how it can be used to inform research directions in silvopastoral systems, globally.

Methodological approach to assessing the quality of strategic planning activities

Subject. The article addresses a methodological approach to determining the feasibility of including an event that ensures the achievement of strategic targets in the implementation plan of a strategic planning document (i.e., a national project or a government program). Objectives. The purpose is to develop a methodological approach to create a balanced list of measures, which, if implemented, will have a positive effect on achieving strategic guidelines for sustainable socio-economic development and strengthening the economic security. Methods. The study rests on expert estimates for calculating the index of activities quality. The calculation of the index is based on the assessment of the index of incoming resources, the index of process, the index of outcome. The approach enables to consider elements associated with the initiation of a particular event, its successful implementation, and achievement of a specific outcome. Results. The study creates an approach to defining the degree of elaboration of the event and the feasibility of including it in the implementation plan of the strategic planning document. The method of expert estimates enables to neutralize some uncertainties and costs caused by initial data quality, empirical estimates of the degree of obtained results’ accuracy, and allocated resources. Conclusions. The working out of organizational, legal, and regulatory measures is only one element of strategizing. Further research should develop methodological approaches to the definition of targeted and critical values of the strategy system to implement a high-quality and operational monitoring.

Neuropsychological Characterization of Aggressive Behavior in Children and Adolescents with CD/ODD and Effects of Single Doses of Medications: The Protocol of the Matrics_WP6-1 Study

Aggressive behaviors and disruptive/conduct disorders are some of the commonest reasons for referral to youth mental health services; nevertheless, the efficacy of therapeutic interventions in real-world clinical practice remains unclear. In order to define more appropriate targets for innovative pharmacological therapies for disruptive/conduct disorders, the European Commission within the Seventh Framework Programme (FP7) funded the MATRICS project (Multidisciplinary Approaches to Translational Research in Conduct Syndromes) to identify neural, genetic, and molecular factors underpinning the pathogenesis of aggression/antisocial behavior in preclinical models and clinical samples. Within the program, a multicentre case-control study, followed by a single-blind, placebo-controlled, cross-over, randomized acute single-dose medication challenge, was conducted at two Italian sites. Aggressive children and adolescents with conduct disorder (CD) or oppositional defiant disorder (ODD) were compared to the same age (10–17 y) typically developing controls (TDC) on a neuropsychological tasks battery that included both “cold” (e.g., inhibitory control, decision making) and “hot” executive functions (e.g., moral judgment, emotion processing, risk assessment). Selected autonomic measures (heart rate variability, skin conductance, salivary cortisol) were recorded before/during/after neuropsychological testing sessions. The acute response to different drugs (methylphenidate/atomoxetine, risperidone/aripiprazole, or placebo) was also examined in the ODD/CD cohort in order to identify potential neuropsychological/physiological mechanisms underlying aggression. The paper describes the protocol of the clinical MATRICS WP6-1 study, its rationale, the specific outcome measures, and their implications for a precision medicine approach.

Chaperones drive in vitro evolution of uracil glycosylase towards misfolded states

Evolution is driven by random mutations, whose fitness outcome is tested over time. In vitro evolution of a library of a randomly mutated protein mimics this process, however, on a short time scale, driven by a specific outcome (such as binding to a bait). Here, we used directed in vitro evolution to investigate the role of molecular chaperones in curbing promiscuity in favor of specificity of protein-protein interactions. Using yeast surface display, we generated a random library of the E. coli protein Uracil glycosylase (UNG), and selected it against various baits. Those included the purified chaperones GroEL, DnaK+DnaJ+ATP, or total protein extracts from WT or delta DnaK+DnaJ cells. We show that in-vitro evolution differs from natural evolution in cells, both physically and thermodynamically. We found that chaperones, whether purified or as part of the protein extract, select for and thus enrich uracil glycosylase (UNG) misfolded species during this in vitro evolution process. In a more general context, our results show that chaperones purge promiscuous misfolded clones from the system, and thereby avoiding their detrimental effects, such as forming wrong interactions with other macromolecules, including proteins, which can harm proteostasis.

Preserved periprosthetic bone stock at 5 years post-operatively with uncemented short hip stem in both collared and collarless version

Introduction Previous bone density studies have generally shown bone resorption around both cemented and uncemented total hip arthroplasty (THA) stems. This is presumed to be due to stress shielding. Short stems have been introduced partly to preserve bone in the proximal femur by a more physiological loading of the bone. The purpose of this study was to evaluate bone remodeling around a short, fully hydroxyapatite-coated titanium stem that comes in a collared and collarless version. Patients and methods A prospective cohort of 50 patients included in a study evaluating the Furlong Evolution stem has been followed for 5 years. Examination was done with dual energy X-ray absorptiometry (DXA) postoperatively, at 1, 2 and 5 years. Clinical outcome was followed with radiography and both general and hip specific outcome measures. Results The two versions of the stem behaved similarly regarding bone remodeling. After an initial decrease up to 1 year, bone mineral density (BMD) increased in all Gruen zones up to 2 years and at 5 years bone stock was still preserved compared with postoperatively (net BMD + 1.2% (95% CI − 0.4 to 2.8)). Increase in BMD occurred mainly in the greater trochanter and distally around the stem with a decrease in the calcar area. Both versions showed excellent clinical outcome up to 5 years. Conclusion This short stem seems to preserve proximal bone stock up to 5 years, exhibiting similar behaviour both with and without a collar. Trial registration number and date of registration ClinicalTrials.gov, (identifier: NCT01894854). July 10, 2013.

Evaluation of a Diagnostic-Therapeutic Algorithm for Finger Epiphyseal Growth Plate Stress Injuries in Adolescent Climbers

Background: Finger epiphyseal growth plate stress injuries are the most frequent sport-specific injuries in adolescent climbers. Definitive diagnostic and therapeutic guidelines are pending. Purpose: To evaluate a diagnostic-therapeutic algorithm for finger epiphyseal growth plate stress injuries in adolescent climbers. Study Design: Case series; Level of evidence, 4. Methods: On the basis of previous work on diagnostics and treatment of finger epiphyseal growth plate stress injuries (EGPIs) in adolescent climbers, we developed a new algorithm for management of these injuries, which was implemented into our clinical work. During a 4-year period, we performed a prospective multicentered analysis of our patients treated according to the algorithm. Climbing-specific background was evaluated (training years, climbing level, training methods, etc); injuries were analyzed (Salter-Harris classification and UIAA MedCom score [Union Internationale des Associations d’Alpinisme]); and treatments and outcomes were recorded: union, time to return to climbing, VAS (visual analog scale), QuickDASH (shortened version of the Disabilities of the Arm, Shoulder, and Hand), and a climbing-specific outcome score. Results: Within the observation period, 27 patients with 37 independent EGPIs of the fingers were recorded (mean ± SD age, 14.7 ± 1.5 years; 19 male, 8 female; 66.7% competitive athletes). Regarding maturity at time of injury, the mean age at injury did not differ by sex. Average UIAA climbing level was 9.5 ± 0.8, with 6 ± 4.6 years of climbing or bouldering and 14 ± 9.1 hours of weekly climbing-specific training volume. Among the 37 injuries there were 7 epiphyseal strains, 2 Salter-Harris I fractures, and 28 Salter-Harris III fractures (UIAA 1, n = 7; UIAA 2, n = 30). Thirty-six injuries developed through repetitive stress, while 1 had an acute onset. Twenty-eight injuries were treated nonoperatively and 9 surgically. Osseous union was achieved in all cases, and there were no recurrences. The time between the start of treatment and the return to sport was 40.1 ± 65.2 days. The climbing-specific outcome score was excellent in 34 patients and good in 3. VAS decreased from 2.3 ± 0.6 to 0.1 ± 0.4 after treatment and QuickDASH from 48.1 ± 7.9 to 28.5 ± 3.3. Conclusion: The proposed management algorithm led to osseous union in all cases. Effective treatment of EGPIs of the fingers may include nonsurgical or surgical intervention, depending on the time course and severity of the injury. Further awareness of EGPI is important to help prevent these injuries in the future.