Identification of high-performing antibodies for the reliable detection of Tau proteoforms by Western blotting and immunohistochemistry.

Antibodies are essential research tools whose performance directly impacts research conclusions and reproducibility. Owing to its central role in Alzheimer's disease and other dementias, hundreds of distinct antibody clones have been developed against the microtubule-associated protein Tau and its multiple proteoforms. Despite this breadth of offer, limited understanding of their performance and poor antibody selectivity have hindered research progress. Here, we validate a large panel of Tau antibodies by Western blot (79 reagents) and immunohistochemistry (35 reagents). We address the reagents' ability to detect the target proteoform, selectivity, the impact of protein phosphorylation on antibody binding and performance in human brain samples. While most antibodies detected Tau at high levels, many failed to detect it at lower, endogenous levels. By WB, non-selective binding to other proteins affected over half of the antibodies tested, with several cross-reacting with the related MAP2 protein, whereas the "oligomeric Tau" T22 antibody reacted with monomeric Tau by WB, thus calling into question its specificity to Tau oligomers. Despite the presumption that "total" Tau antibodies are agnostic to post-translational modifications, we found that phosphorylation partially inhibits binding for many such antibodies, including the popular Tau-5 clone. We further combine high-sensitivity reagents, mass-spectrometry proteomics and cDNA sequencing to demonstrate that presumptive Tau "knockout" human cells continue to express residual protein arising through exon skipping, providing evidence of previously unappreciated gene plasticity. Finally, probing of human brain samples with a large panel of antibodies revealed the presence of C-term-truncated versions of all main Tau brain isoforms in both control and tauopathy donors. Ultimately, we identify a validated panel of Tau antibodies that can be employed in Western blotting and/or immunohistochemistry to reliably detect even low levels of Tau expression with high selectivity. This work represents an extensive resource that will enable the re-interpretation of published data, improve reproducibility in Tau research, and overall accelerate scientific progress.

Incidence of Subsequent Mental Health Disorders and Social Adversity Following Pediatric Concussion: A Longitudinal, Population-Based Study.

OBJECTIVE: To determine the long-term risk of new adverse psychosocial outcomes among adolescents diagnosed with a concussion compared with those not diagnosed. STUDY DESIGN: A retrospective, population-based cohort study was conducted. Adolescents (10-18 years) with a physician-diagnosed concussion between 2000 and 2005 were matched on neighborhood and age with 5 controls without concussion from the general population. New-onset mental health disorders, medication use, social, and justice outcomes were extracted using datasets linked to the population data repository. Adolescents were followed for 11-16 years. Adjusted hazard ratios (95% CIs) were estimated. RESULTS: In total, 2082 adolescents with a concussion were matched to 10 510 without. Adolescents with a concussion had an increased risk of any mental health disorder (HR 1.34; 95% CI 1.25-1.45), mood disorder (HR 1.30; 95% 1.18-1.43), psychosis (HR 1.43; 95% CI 1.18-1.74), substance abuse disorder (HR 1.67; 95% 1.31-2.14), and receiving a psychotropic prescription (HR 1.31; 95% CI 1.20-1.42). Female adolescents had an increased risk of ADHD following concussion (HR 1.89; 95% CI 1.17-3.05). Adolescents with a concussion had an increased risk of being accused (HR 1.22; 95% CI 1.11-1.34), victim (HR 1.29; 95% CI 1.11-1.48), or witness (HR 1.16; 95% CI 1.01-1.32) of a crime, or contact with Child and Family Services (HR 1.33; 95% CI 1.10-1.62). There was no association between concussion and attempting or completing suicide, receiving housing support, or collecting income support. CONCLUSIONS: Concussion was associated with an increased risk for multiple adverse psychosocial outcomes. Future work should focus on early identification of those at risk of these outcomes to help optimize longitudinal medical care and support.

Current Use and Future Considerations for Concussion Telemedicine Healthcare in Canada.

OBJECTIVE: To examine the use of telemedicine among Canadian concussion providers and clinics before and after the COVID-19 pandemic onset and identify barriers and facilitators for future use. METHODS: Ninety-nine concussion clinics and healthcare providers across Canada that offered one or more clinical concussion-related service were identified using standardized online searches and approached to complete a cross-sectional online survey. RESULTS: Thirty clinics or providers completed the survey and two completed subsections of the survey (response rate of 32.3%). Only 28.1% of respondents indicated that they used telemedicine to provide care prior to the COVID-19 pandemic. Providers most commonly using telemedicine prior to the pandemic were occupational therapists and physicians, while the most commonly used services were in-person videoconferencing and eConsultation. Most respondents (87%) indicated their clinic's use of telemedicine changed following the onset of the COVID-19 pandemic including new use of in-person video-conferencing, telephone calls, and eConsultation. Ninety-three percent indicated that they would consider using telemedicine to provide care to their concussion patients once the pandemic was over. Barriers needed to be overcome to facilitate use or greater use of telemedicine-based services were the inability to conduct a complete physical examination, lack of appropriate reimbursement, lack of start-up, and maintenance funding and medico-legal risk. CONCLUSION: Telemedicine was used by a minority of Canadian concussion clinics and providers prior to the COVID-19 pandemic but was rapidly adopted by many facilities. This study provides important insight into the factors that must be considered to optimize use of telemedicine in concussion care in the future.

Clinical Outcomes of Pediatric Acute Sport- and Non-Sport-Related Concussions.

OBJECTIVES: The objectives were to examine clinical characteristics, length of recovery, and the prevalence of delayed physician-documented recovery, compare clinical outcomes among those with sport-related concussion (SRC) and non-sport-related concussion (nSRC), and identify risk factors for delayed recovery. METHODS: Included patients (8-18 years) were assessed ≤14 days post-injury at a multidisciplinary concussion program and diagnosed with an acute SRC or nSRC. Physician-documented clinical recovery was defined as returning to pre-injury symptom status, attending full-time school without symptoms, completing Return-to-Sport strategy as needed, and normal physical examination. Delayed physician-documented recovery was defined as >28 days post-injury. RESULTS: Four hundred and fifteen patients were included (77.8% SRC). There was no difference in loss of consciousness (SRC: 9.9% vs nSRC: 13.0%, p = 0.39) or post-traumatic amnesia (SRC: 24.1% vs SRC: 31.5%, p = 0.15) at the time of injury or any differences in median Post-Concussion Symptom Scale scores (SRC: 20 vs nSRC: 23, p = 0.15) at initial assessment. Among those with complete clinical follow-up, the median physician-documented clinical recovery was 20 days (SRC: 19 vs nSRC: 23; p = 0.37). There was no difference in the proportion of patients who developed delayed physician-documented recovery (SRC: 27.7% vs nSRC: 36.1%; p = 0.19). Higher initial symptom score increased the risk of delayed physician-documented recovery (IRR: 1.39; 95% CI: 1.29, 1.49). Greater material deprivation and social deprivation were associated with an increased risk of delayed physician-documented recovery. CONCLUSIONS: Most pediatric concussion patients who undergo early medical assessment and complete follow-up appear to make a complete clinical recovery within 4 weeks, regardless of mechanism.

Addressing the Shadow Pandemic: COVID-19 Related Impacts, Barriers, Needs, and Priorities to Health Care and Support for Women Survivors of Intimate Partner Violence and Brain Injury.

Intimate partner violence (IPV) affects 1 in 3 women and has intensified during the COVID-19 pandemic. Although most injuries are to the head, face, and neck, leaving survivors vulnerable to sustaining traumatic brain injury (TBI), the intersection of IPV and TBI remains largely unrecognized. This article reports on COVID-19-related effects, barriers, needs, and priorities to health care and support services for women survivors of IPV-TBI. Using a participatory research model, we engaged 30 stakeholders in virtual meetings drawn from an IPV-TBI Knowledge to Practice Network in two virtual meetings. Stakeholders included women survivors, service providers, researchers, and decision makers across the IPV, TBI, and healthcare sectors. Data were gathered through small group breakout sessions facilitated by the research team using semistructured discussion guides. Sessions were recorded, transcribed verbatim, and analyzed using thematic analysis techniques. Stakeholders were given the opportunity to contribute to the analysis and knowledge transfer through member checking activities. Ethics approval was obtained through the University of Toronto. Stakeholders shared that COVID-19 has increased rates and severity of IPV and barriers to services and help-seeking. These effects have been exacerbated by infrastructure difficulties in rural and remote areas, including limited access to services. They noted the need to carefully consider implications of virtual care such as safety, privacy, and usability. Requests from survivors for peer support have increased significantly, indicating a need for more formalized and better-supported peer roles. Stakeholders further noted that an overwhelming lack of awareness of the intersection of IPV-TBI continues. Increasing education and awareness among health care and IPV service providers, survivors, and the public remains a priority. The COVID-19 pandemic has intensified IPV-TBI, increased challenges for women survivors, and accentuated the continued lack of IPV-TBI awareness. Key recommendations for health care and rehabilitation to address this priority are discussed.

The Intersection of Intimate Partner Violence and Traumatic Brain Injury: Findings From an Emergency Summit Addressing System-Level Changes to Better Support Women Survivors.

BACKGROUND: Traumatic brain injury (TBI) occurring during intimate partner violence (IPV) is a largely unrecognized but significant public health crisis. One in 3 women will experience IPV in their lifetime, up to 75% of whom will sustain a TBI as a result. This article reports on the systems-level findings from a national summit to address barriers, needs, and priorities related to healthcare and support services for women survivors of IPV-TBI. OBJECTIVES: (1) To identify key needs, facilitators, and barriers to care for women survivors of IPV presenting with TBI; and (2) to cocreate ideas for resources and principles for identification, clinical care, and support for healthcare practitioners who treat women exposed to IPV and TBI. METHODS: Using a community-based participatory research approach, we engaged 30 stakeholders-drawn from a national IPV-TBI Knowledge-to-Practice (K2P) Network including diverse women survivors, service providers, researchers, and decision makers-in 2 half-day virtual meetings. Data were gathered through small group breakout sessions using semistructured discussion guides. Sessions were recorded, transcribed verbatim, and analyzed using thematic analysis techniques. Stakeholders contributed to the analysis and knowledge translation through member-checking activities. Ethics approval was obtained through the University of Toronto. FINDINGS: Three main systems-level themes arose during these discussions: (1) the need for trauma-informed, anti-racist, and equitable health and social care systems; (2) the need for cross-pollination of knowledge between disciplines; and (3) the need for systems-level support for integrated and coordinated care. This article explores these needs and provides recommendations and suggestions for paths forward. CONCLUSIONS: The findings of this project enhance understanding of system-level needs among women survivors and provide a template for a national agenda for IPV-TBI research and practice.

RNA surveillance by uridylation-dependent RNA decay in Schizosaccharomyces pombe.

Uridylation-dependent RNA decay is a widespread eukaryotic pathway modulating RNA homeostasis. Terminal uridylyltransferases (Tutases) add untemplated uridyl residues to RNA 3'-ends, marking them for degradation by the U-specific exonuclease Dis3L2. In Schizosaccharomyces pombe, Cid1 uridylates a variety of RNAs. In this study, we investigate the prevalence and impact of uridylation-dependent RNA decay in S. pombe by transcriptionally profiling cid1 and dis3L2 deletion strains. We found that the exonuclease Dis3L2 represents a bottleneck in uridylation-dependent mRNA decay, whereas Cid1 plays a redundant role that can be complemented by other Tutases. Deletion of dis3L2 elicits a cellular stress response, upregulating transcription of genes involved in protein folding and degradation. Misfolded proteins accumulate in both deletion strains, yet only trigger a strong stress response in dis3L2 deficient cells. While a deletion of cid1 increases sensitivity to protein misfolding stress, a dis3L2 deletion showed no increased sensitivity or was even protective. We furthermore show that uridylyl- and adenylyltransferases cooperate to generate a 5'-NxAUUAAAA-3' RNA motif on dak2 mRNA. Our studies elucidate the role of uridylation-dependent RNA decay as part of a global mRNA surveillance, and we found that perturbation of this pathway leads to the accumulation of misfolded proteins and elicits cellular stress responses.

Benign Paroxysmal Positional Vertigo After Pediatric Sports-Related Concussion.

OBJECTIVE: Report the clinical findings and outcomes among pediatric patients diagnosed with benign paroxysmal positional vertigo (BPPV) after sports-related concussion (SRC). DESIGN: Retrospective case series. SETTING: Multidisciplinary pediatric concussion program. PATIENTS: Patients younger than 19 years with a sport or recreation activity-related concussion referred for comprehensive vestibular physiotherapy assessment. MAIN OUTCOME MEASURE: Symptom resolution after targeted particle repositioning (PR). RESULTS: During the study period, 115 pediatric SRC patients underwent vestibular physiotherapy assessment including 12 (10.4%) who were diagnosed with BPPV. Unilateral posterior semicircular canal (SCC) BPPV was diagnosed in 8/12 (75%) patients, and unilateral anterior SCC BPPV diagnosed in 4/12 (25%) patients. Benign paroxysmal positional vertigo was successfully treated in all patients with a mean of 1.58 targeted PR maneuvers (range = 1-4). CONCLUSIONS: Comprehensive management of pediatric SRC requires a multidisciplinary approach to address the heterogeneous pathophysiology of persistent postconcussion symptoms. Pediatric SRC patients with coexisting BPPV should be considered for targeted PR.

A transposon-derived small RNA regulates gene expression in Salmonella Typhimurium.

Bacterial sRNAs play an important role in regulating many cellular processes including metabolism, outer membrane homeostasis and virulence. Although sRNAs were initially found in intergenic regions, there is emerging evidence that protein coding regions of the genome are a rich reservoir of sRNAs. Here we report that the 5΄UTR of IS200 transposase mRNA (tnpA) is processed to produce regulatory RNAs that affect expression of over 70 genes in Salmonella Typhimurium. We provide evidence that the tnpA derived sRNA base-pairs with invF mRNA to repress expression. As InvF is a transcriptional activator of SPI-1 encoded and other effector proteins, tnpA indirectly represses these genes. We show that deletion of IS200 elements in S. Typhimurium increases invasion in vitro and reduces growth rate, while over-expression of tnpA suppresses invasion. Our work indicates that tnpA acts as an sRNA 'sponge' that sets a threshold for activation of Salmonella pathogenicity island (SPI)-1 effector proteins and identifies a new class of 'passenger gene' for bacterial transposons, providing the first example of a bacterial transposon producing a regulatory RNA that controls host gene expression.

Cervical Spine Dysfunction Following Pediatric Sports-Related Head Trauma.

OBJECTIVE: To examine the prevalence of cervical spine injuries among children and adolescents referred with suspected and diagnosed sports-related concussion (SRC); and evaluate the effect of cervical spine dysfunction (CSD) on physician-documented clinical recovery following SRC. SETTING: A multidisciplinary pediatric concussion program. PARTICIPANTS: A total of 266 patients (6-19 years) referred with suspected SRC. DESIGN: A retrospective cohort study. MAIN MEASURES: CSD defined as neurological symptoms localized to the cervical spine or the presence of neck pain, headache, or dizziness and abnormal cervical spine examination findings; physician-documented clinical recovery. RESULTS: One patient was diagnosed with a T1 compression fracture. Of the 246 patients diagnosed with SRC, 80 (32.5%) met the clinical criteria for CSD including 4 patients with central cord neuropraxia and 1 with a spinal cord injury without radiographic abnormality (SCIWORA). Excluding patients with central cord neuropraxia OR SCIWORA, patients with SRC with CSD took longer to achieve physician-documented clinical recovery (28.5 days vs 17 days, P < .0001) and were 3.95 times more likely to experience delayed physician-documented clinical recovery (>4 weeks postinjury) compared with those without CSD. CONCLUSIONS: Patients with suspected and diagnosed SRC can present with a wide spectrum of coincident cervical spine injuries. Cervical spine dysfunction may be a risk factor for delayed clinical recovery.

Primary care management of concussion in Canada.

Concussion has emerged as an important public health issue affecting thousands of Canadians annually. Health care providers including paediatricians, family and emergency medicine physicians, nurses, and nurse practitioners are commonly tasked with the responsibility of providing primary care to patients with acute concussion and those with persistent post-concussion symptoms. In July 2017, Parachute, in collaboration with the Public Health Agency of Canada and Sport Canada released the Canadian Guideline on Concussion in Sport that outlines a standardized and evidence-based approach to the recognition, diagnosis, and management of youth and adults with suspected concussion. In this report, we provide a brief overview of the important roles of primary care providers in the medical assessment, management, and prevention of concussion as outlined in this national best practice guideline.

Silent but deadly: IS200 promotes pathogenicity in Salmonella Typhimurium.

Bacterial transposons were long thought of as selfish mobile genetic elements that propagate at the expense of 'host' bacterium fitness. However, limited transposition can benefit the host organism by promoting DNA rearrangements and facilitating horizontal gene transfer. Here we discuss and provide context for our recently published work which reported the surprising finding that an otherwise dormant transposon, IS200, encodes a regulatory RNA in Salmonella Typhimurium. This previous work identified a trans-acting sRNA that is encoded in the 5'UTR of IS200 transposase mRNA (tnpA). This sRNA represses expression of genes encoded within Salmonella Pathogenicity Island 1 (SPI-1), and accordingly limits invasion into non-phagocytic cells in vitro. We present new data here that shows IS200 elements are important for colonization of the mouse gastrointestinal tract. We discuss our previous and current findings in the context of transposon biology and suggest that otherwise 'silent' transposons may in fact play an important role in controlling host gene expression.

Evaluation of a Medically Supervised Concussion Protocol for Youth Hockey in Canada.

OBJECTIVES: The objective of this study was to evaluate the feasibility and implementation of a standardized medically supervised concussion protocol established between a city-wide AAA hockey league and a multi-disciplinary concussion program. METHODS: We conducted a retrospective review of injury surveillance, clinical and healthcare utilization data from all athletes evaluated and managed through the Winnipeg AAA Hockey concussion protocol during the 2016-2017 season. We also conducted post-season email surveys of head coaches and parents responsible for athletes who competed in the same season. RESULTS: During the 2016-2017 season, 28 athletes were evaluated through the medically supervised concussion protocol, with two athletes undergoing evaluation for repeat injuries (a total of 30 suspected injuries and consultations). In all, 96.7% of the athletes managed through the concussion protocol were captured by the league-designated Concussion Protocol Coordinator and 100% of eligible athletes underwent complete medical follow-up and clearance to return to full hockey activities. Although 90% of responding head coaches and 91% of parents were aware of the concussion protocol, survey results suggest that some athletes who sustained suspected concussions were not managed through the protocol. Head coaches and parents also indicated that athlete education and communication between medical and sport stakeholders were other elements of the concussion protocol that could be improved. CONCLUSION: Successful implementation of a medically supervised concussion protocol for youth hockey requires clear communication between sport stakeholders and timely access to multi-disciplinary experts in traumatic brain and spine injuries. Standardized concussion protocols for youth sports may benefit from periodic evaluations by sport stakeholders and incorporation of national guideline best practices and resources.

Concussion education in Canadian medical schools: a 5 year follow-up survey.

BACKGROUND: Despite concussion now being recognized as a public health priority in Canada, recent studies-including our 2012 survey of Canadian medical schools-have revealed major gaps in concussion education at the undergraduate medical school level. METHODS: We re-surveyed all 17 Canadian medical schools using a questionnaire divided in two categories: (1) concussion-specific education (2) head injury education incorporating a concussion component to determine whether there have been any improvements in concussion education at the medical school level during the last five years. For each year of medical school, respondents were asked to provide the estimated number of hours and teaching format for each category. RESULTS: We received replies from 13 of the 17 medical schools (76%). 11 of the 13 (85%) medical schools now reported providing concussion-specific education compared to 29% in our 2012 survey. The mean number of hours dedicated to category 1 learning in 2017 was 2.65 h compared to 0.57 in 2012, and the mean number of hours of category 2 increased to 7.5 from 1.54. CONCLUSION: Our follow-up study reveals increased exposure to concussion-related teaching in Canadian medical schools during the last five years. Persistent deficiencies in a minority of schools are highlighted. These should be addressed by reiterating the importance of concussion education for undergraduate medical students and by developing clear concussion-specific objectives at the national licensure level.

Legislation for Youth Sport Concussion in Canada: Review, Conceptual Framework, and Recommendations.

In this article, we conduct a review of introduced and enacted youth concussion legislation in Canada and present a conceptual framework and recommendations for future youth sport concussion laws. We conducted online searches of federal, provincial, and territorial legislatures to identify youth concussion bills that were introduced or successfully enacted into law. Internet searches were carried out from July 26 and 27, 2016. Online searches identified six youth concussion bills that were introduced in provincial legislatures, including two in Ontario and Nova Scotia and one each in British Columbia and Quebec. One of these bills (Ontario Bill 149, Rowan's Law Advisory Committee Act, 2016) was enacted into provincial law; it is not actual concussion legislation, but rather a framework for possible enactment of legislation. Two bills have been introduced in federal parliament but neither bill has been enacted into law. At present, there is no provincial or federal concussion legislation that directly legislates concussion education, prevention, management, or policy in youth sports in Canada. The conceptual framework and recommendations presented here should be used to guide the design and implementation of future youth sport concussion laws in Canada.

Graded Aerobic Treadmill Testing in Adolescent Traumatic Brain Injury Patients.

PURPOSE: To examine the safety and tolerability of clinical graded aerobic treadmill testing in recovering adolescent moderate and severe traumatic brain injury (TBI) patients referred to a multidisciplinary pediatric concussion program. METHODS: We completed a retrospective case series of two moderate and five severe TBI patients (mean age, 17.3 years) who underwent initial Buffalo Concussion Treadmill Testing at a mean time of 71.6 days (range, 55-87) postinjury. RESULTS: Six patients completed one graded aerobic treadmill test each and one patient underwent initial and repeat testing. There were no complications. Five initial treadmill tests were completely tolerated and allowed an accurate assessment of exercise tolerance. Two initial tests were terminated early by the treatment team because of neurological and cardiorespiratory limitations. As a result of testing, two patients were cleared for aerobic exercise as tolerated and four patients were treated with individually tailored submaximal aerobic exercise programs resulting in subjective improvement in residual symptoms and/or exercise tolerance. Repeat treadmill testing in one patient performed after 1 month of treatment with submaximal aerobic exercise prescription was suggestive of improved exercise tolerance. One patient was able to tolerate aerobic exercise following surgery for posterior glottic stenosis. CONCLUSIONS: Preliminary results suggest that graded aerobic treadmill testing is a safe, well tolerated, and clinically useful tool to assess exercise tolerance in appropriately selected adolescent patients with TBI. Future prospective studies are needed to evaluate the effect of tailored submaximal aerobic exercise prescription on exercise tolerance and patient outcomes in recovering adolescent moderate and severe TBI patients.

Multidisciplinary Management of Pediatric Sports-Related Concussion.

OBJECTIVES: To summarize the clinical characteristics and outcomes of pediatric sports-related concussion (SRC) patients who were evaluated and managed at a multidisciplinary pediatric concussion program and examine the healthcare resources and personnel required to meet the needs of this patient population. METHODS: We conducted a retrospective review of all pediatric SRC patients referred to the Pan Am Concussion Program from September 1st, 2013 to May 25th, 2015. Initial assessments and diagnoses were carried out by a single neurosurgeon. Return-to-Play decision-making was carried out by the multidisciplinary team. RESULTS: 604 patients, including 423 pediatric SRC patients were evaluated at the Pan Am Concussion Program during the study period. The mean age of study patients was 14.30 years (SD: 2.32, range 7-19 years); 252 (59.57%) were males. Hockey (182; 43.03%) and soccer (60; 14.18%) were the most commonly played sports at the time of injury. Overall, 294 (69.50%) of SRC patients met the clinical criteria for concussion recovery, while 75 (17.73%) were lost to follow-up, and 53 (12.53%) remained in active treatment at the end of the study period. The median duration of symptoms among the 261 acute SRC patients with complete follow-up was 23 days (IQR: 15, 36). Overall, 25.30% of pediatric SRC patients underwent at least one diagnostic imaging test and 32.62% received referral to another member of our multidisciplinary clinical team. CONCLUSION: Comprehensive care of pediatric SRC patients requires access to appropriate diagnostic resources and the multidisciplinary collaboration of experts with national and provincially-recognized training in TBI.

A cis-encoded sRNA, Hfq and mRNA secondary structure act independently to suppress IS200 transposition.

IS200 is found throughout Enterobacteriaceae and transposes at a notoriously low frequency. In addition to the transposase protein (TnpA), IS200 encodes an uncharacterized Hfq-binding sRNA that is encoded opposite to the tnpA 5'UTR. In the current work we asked if this sRNA represses tnpA expression. We show here that the IS200 sRNA (named art200 for antisense regulator of transposase IS200) basepairs with tnpA to inhibit translation initiation. Unexpectedly, art200-tnpA pairing is limited to 40 bp, despite 90 nt of perfect complementarity. Additionally, we show that Hfq and RNA secondary structure in the tnpA 5'UTR each repress tnpA expression in an art200-independent manner. Finally, we show that disrupting translational control of tnpA expression leads to increased IS200 transposition in E. coli. The current work provides new mechanistic insight into why IS200 transposition is so strongly suppressed. The possibility of art200 acting in trans to regulate a yet-unidentified target is discussed as well as potential applications of the IS200 system for designing novel riboregulators.

Googling Concussion Care: A Critical Appraisal of Online Concussion Healthcare Providers and Practices in Canada.

BACKGROUND: Concussion is an emerging public health concern, but care of patients with a concussion is presently unregulated in Canada. METHODS: Independent, blinded Google Internet searches were conducted for the terms "concussion" and "concussion clinic" and each of the Canadian provinces and territories. The first 10 to 15 concussion healthcare providers per province were identified. A critical appraisal of healthcare personnel and services offered on the provider's Web site was conducted. RESULTS: Fifty-eight concussion healthcare providers were identified using this search methodology. Only 40% listed the presence of an on-site medical doctor (M.D.) as a member of the clinical team. Forty-seven percent of concussion healthcare providers advertised access to a concussion clinic, program, or center on their Web site. Professionals designated as team leaders, directors, or presidents among concussion clinics, programs, and centers included a neuropsychologist (15%), sports medicine physician (7%), neurologist (4%), and neurosurgeon (4%). Services offered by providers included baseline testing (67%), physiotherapy (50%), and hyperbaric oxygen therapy (2%). CONCLUSIONS: This study indicates that there are numerous concussion healthcare providers in Canada offering diverse services with clinics operated by professionals with varying levels of training in traumatic brain injury. In some cases, the practices of these concussion clinics do not conform to current expert consensus guidelines.

Migraine with Aura or Sports-Related Concussion: Case Report, Pathophysiology, and Multidisciplinary Approach to Management.

The evaluation and management of athletes presenting with clinical features of migraine headache with aura in the setting of sports-related head trauma is challenging. We present a case report of a 15-yr-old boy with a history of migraine with visual aura that developed acute visual disturbance and headache after a head injury during an ice hockey game. The patient underwent comprehensive assessment at a multidisciplinary concussion program, including neuro-ophthalmological examination, neurocognitive testing, and graded aerobic treadmill testing. Clinical history and multidisciplinary assessment was consistent with the diagnosis of coexisting sports-related concussion and migraine with brainstem aura. The authors discuss the pearls and pitfalls of managing patients who develop migraine headache with visual aura after sports-related head injury and the value of a comprehensive multidisciplinary approach to this unique patient population.