Premortem Chronic Traumatic Encephalopathy Diagnoses in Professional Football.

OBJECTIVE: American-style football (ASF) has gained attention because of possible links between repetitive head injury and neurodegenerative diseases. Although postmortem pathologic changes consistent with chronic traumatic encephalopathy (CTE) have been reported in ASF players, there are currently no established premortem diagnostic criteria for CTE. Nevertheless, presented with symptoms of cognitive impairment, clinicians treating former players may be inclined to suggest CTE without a thorough exploration of comorbid factors that demonstrate similar clinical phenotypes to putative CTE. METHODS: A survey of 3,913 former ASF players aged 24 to 89 was conducted for those who responded by March 2019. RESULTS: Despite being a postmortem diagnosis, 108 players (2.8%) self-reported clinician-diagnosed CTE. The percentage of players under age 60 years reporting a CTE diagnosis was 2.3% versus 3.7% in participants age 60 or older. Comorbidities in participants self-reporting CTE were significantly more common, including sleep apnea, hypercholesterolemia, obesity, indicators of past or current depression, hypertension, prescription pain medication use, heart conditions, and low testosterone when compared to non-CTE respondents. Patterns of reporting for obesity, hypertension, heart conditions, or hypercholesterolemia differed between older and younger participants. Cognitive impairment symptoms were significantly higher in participants self-reporting CTE. INTERPRETATION: Some former professional football players have been clinically diagnosed with CTE, a postmortem condition. Comorbidities that can affect cognition were associated with CTE diagnoses in both older and younger players. Although underlying neuropathology cannot be ruled out, treatable conditions should be explored in former athletes demonstrating CTE-linked clinical phenotypes or symptoms as a means of improving cognitive health in these patients. ANN NEUROL 2020 ANN NEUROL 2020;88:106-112.

FDG PET-CT imaging in head and neck paragangliomas: A centre experience.

Head and neck paragangliomas (HNPGLs) are rare tumours with ~ 30% genetic mutations, mainly in succinate dehydrogenase (SDHx) genes. The utility of FDG PET-CT in HNPGLs is questioned by recent developments in novel radiotracers. We therefore performed a retrospective study in a single tertiary referral centre to address the utility of FDG PET/CT in HNPGLs. METHODS: Clinical data on genetic testing and follow-up were collected for patients who had FDG PET-CT scans from 2004 to 2016. Receiver operator characteristic (ROC) analysis was used to compare standardized uptake values (SUVs), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) between lesions in patients who had a clinically related event: event (+) and those who did not: event (-). Similarly, we compared PET parameters between SDHx+ patients and a control group with low probability of mutation. RESULTS: Of 153 HNPGL patients, 73 (29 SDHx+) with 93 FDG-positive lesions were identified: 53.8% of lesions were assessed in a pre-therapeutic setting. In comparison with a reference extracted from clinicoradiological database, FDG PET-CT showed good performance to detect HNPGLs (96.6% accuracy). In this study population, 16 disease progression, 1 recurrence and 1 death were recorded and event (+) patients had lesions with higher SUVmax (p = .03 and p = .02, respectively). Conversely, there were no differences in PET parameters between lesions in SDHx+ patients and controls with low probability of SDHx+ mutations. CONCLUSIONS: FDG PET-CT has clinical utility in HNPGLs, mostly before local treatment. There were no significant differences in PET parameters between SDHx patients and a sporadic HNPGL population. However, regardless of SDHx mutation status, a high SUVmax was associated with more clinical events and prompts to a closer follow-up.

Effect of digestion on stability of palivizumab IgG1 in the infant gastrointestinal tract.

BACKGROUND: Potentially, orally administered antibodies specific to enteric pathogens could be administered to infants to prevent diarrheal infections, particularly in developing countries where diarrhea is a major problem. However, to prevent infection, such antibodies would need to resist degradation within the gastrointestinal tract. METHODS: Palivizumab, a recombinant antibody specific to respiratory syncytial virus (RSV), was used in this study as a model for examining the digestion of neutralizing antibodies to enteric pathogens in infants. The survival of this recombinant IgG1 across digestion in 11 infants was assayed via an anti-idiotype ELISA and RSV F protein-specific ELISA. Concentrations were controlled for any dilution or concentration that occurred in the digestive system using mass spectrometry-based quantification of co-administered, orally supplemented, indigestible polyethylene glycol (PEG-28). RESULTS: Binding activity of Palivizumab IgG1 decreased (26-99%) across each phase of in vivo digestion as measured by both anti-idiotype and RSV F protein-specific ELISAs. CONCLUSION: Antibodies generated for passive protection of the infant gastrointestinal tract from pathogens will need to be more resistant to digestion than the model antibody fed to infants in this study, or provided in higher doses to be most effective. IMPACT: Binding activity of palivizumab IgG1 decreased (26-99%) across each phase of in vivo infant digestion as measured by both anti-idiotype and RSV F protein-specific ELISAs. Palivizumab was likely degraded by proteases and changes in pH introduced in the gut. Antibodies generated for passive protection of the infant gastrointestinal tract from pathogens will need to be more resistant to digestion than the model antibody fed to infants in this study, or provided in higher doses to be most effective. The monoclonal antibody IgG1 tested was not stable across the infant gastrointestinal tract. The observation of palivizumab reduction was unlikely due to dilution in the gastrointestinal tract. The results of this work hint that provision of antibody could be effective in preventing enteric pathogen infection in infants. Orally delivered recombinant antibodies will need to either be dosed at high levels to compensate for digestive losses or be engineered to better resist digestion. Provision of enteric pathogen-specific recombinant antibodies to at-risk infants could provide a new and previously unexplored pathway to reducing the infection in infants. The strategy of enteric recombinant antibodies deserves more investigation throughout medicine as a novel means for treatment of enteric disease targets.

15-Deoxy-Δ-12,14-prostaglandin J2 effects in vascular smooth muscle cells: Implications in vascular smooth muscle cell proliferation and contractility.

15-Deoxy-Δ-12,14-prostaglandin J2 (15d-PGJ2) is an endogenous agonist of the ligand dependent transcriptional factor, peroxisome proliferator-activated receptor -gamma (PPAR-γ). Although PPAR-γ mediates some actions of 15d-PGJ2, many actions of 15d-PGJ2 are independent of PPAR-γ. The PPAR-γ signaling pathway has beneficial effects on tumor progression, inflammation, oxidative stress, and angiogenesis in numerous studies. In this review, various studies were analyzed to understand the effects of 15d-PGJ2 in vascular smooth muscle cells (VSMC)s. 15d-PGJ2 inhibits proliferation of VSMCs during vascular remodeling and it alters the expression of contractile proteins and inflammatory components within these cells as well. However, the effects of 15d-PGJ2 as well as its ability to induce PPAR-γ activation remains controversial as contradictory effects of this prostaglandin in VSMCs exist. Understanding the mechanisms by which 15d-PGJ2 elicit beneficial actions whether by PPAR-γ activation or independently, will aid in developing new therapeutic strategies for diseases such as hypertension with an inflammatory component. Although great advances are being made, more research is needed to reach definitive conclusions.

Displaced Gastrostomy Tube in the Pediatric Emergency Department: Implementing an Evidence-based Algorithm and Quality Improvement Project.

INTRODUCTION: ED visits for gastrostomy tube-related complications are common, and many are related to tube displacement. Evidence-based practices can provide standardized care. METHODS: This study was an evidence-based project to develop and implement an algorithm for the care of patients with a displaced gastrostomy tube in the emergency department. Providers were educated on the algorithm, and clinical practice change was evaluated. Provider knowledge was assessed using pretest and posttest; analyses included paired t test. Descriptive statistics of electronic medical record data on confirmation method, documentation, and referral were reported. RESULTS: Provider knowledge was improved after the education (n = 22; t(21) = -3.80; P = 0.001). After the education, procedure notes were used and completed in 95% of the cases. Appropriate use of the confirmation method was present in 95% of the cases, and all cases were referred to the gastrostomy/specialty clinic. DISCUSSION: Educating providers regarding care for displaced gastrostomy tubes increased their knowledge. A standardized algorithm improved care by decreasing the use of contrast studies, improving documentation, and referring patients to the gastrostomy/specialty clinic. This evidence-based algorithm offered health care providers a protocol to ensure consistent care for children in the emergency department and support for families.

CDC Deployments to State, Tribal, Local, and Territorial Health Departments for COVID-19 Emergency Public Health Response - United States, January 21-July 25, 2020.

Coronavirus disease 2019 (COVID-19) is a viral respiratory illness caused by SARS-CoV-2. During January 21-July 25, 2020, in response to official requests for assistance with COVID-19 emergency public health response activities, CDC deployed 208 teams to assist 55 state, tribal, local, and territorial health departments. CDC deployment data were analyzed to summarize activities by deployed CDC teams in assisting state, tribal, local, and territorial health departments to identify and implement measures to contain SARS-CoV-2 transmission (1). Deployed teams assisted with the investigation of transmission in high-risk congregate settings, such as long-term care facilities (53 deployments; 26% of total), food processing facilities (24; 12%), correctional facilities (12; 6%), and settings that provide services to persons experiencing homelessness (10; 5%). Among the 208 deployed teams, 178 (85%) provided assistance to state health departments, 12 (6%) to tribal health departments, 10 (5%) to local health departments, and eight (4%) to territorial health departments. CDC collaborations with health departments have strengthened local capacity and provided outbreak response support. Collaborations focused attention on health equity issues among disproportionately affected populations (e.g., racial and ethnic minority populations, essential frontline workers, and persons experiencing homelessness) and through a place-based focus (e.g., persons living in rural or frontier areas). These collaborations also facilitated enhanced characterization of COVID-19 epidemiology, directly contributing to CDC data-informed guidance, including guidance for serial testing as a containment strategy in high-risk congregate settings, targeted interventions and prevention efforts among workers at food processing facilities, and social distancing.

The Football Players' Health Study at Harvard University: Design and objectives.

The Football Players Health Study at Harvard University (FPHS) is a unique transdisciplinary, strategic initiative addressing the challenges of former players' health after having participated in American style football (ASF). The whole player focused FPHS is designed to deepen understanding of the benefits and risks of participation in ASF, identify risks that are potentially reversible or preventable, and develop interventions or approaches to improve the health and wellbeing of former players. We are recruiting and following a cohort of former professional ASF players who played since 1960 (current n = 3785). At baseline, participants complete a self-administered standardized questionnaire, including initial reporting of exposure history and physician-diagnosed health conditions. Additional arms of the initiative are addressing targeted studies, including promising primary, secondary, and tertiary interventions; extensive in-person clinical phenotyping, and legal and ethical concerns of the play. This paper describes the components of the FPHS studies undertaken and completed thus far, as well as those studies currently underway or planned for the near future. We present our initiatives herein as a potential paradigm of one way to proceed (acknowledging that it is not the only way). We share what we have learned so that it may be useful to others, particularly in regard to trying to make professional sports meet the needs of multiple stakeholders ranging from players to owners, to fans, and possibly even to parents making decisions for their children.

Astrocytes and the Renin Angiotensin System: Relevance in Disease Pathogenesis.

The presence of a brain renin angiotensin system (RAS) is well documented. An overactive brain RAS contributes to the development and progression of cardiovascular and renal disorders among other conditions. In hypertension, an augmented brain RAS leads to an increase in sympathetic nervous system activity. In addition, impaired baroreceptor reflex function, increased vasopressin activity and neuroinflammation are important contributors as well. The relevance of angiotensins in central and peripheral systems, such as neurons and vascular smooth muscle cells, in cardiovascular disease pathogenesis is fairly understood. However, the role of astrocytes is less well studied. Astrocytes are a major contributor to neuroinflammation by increased synthesis and secretion of inflammatory mediators, dysregulated astrogliosis and impaired astrocyte proliferation. Astrocytes may also contribute to impaired neuromodulation. The precise molecular mechanisms by which astrocytes mediate these effects are still not fully understood. Here, we summarize the role of astrocytes in RAS -mediated pathogenesis of hypertension and other cardiovascular diseases.

Addressing Childhood Obesity for Type 2 Diabetes Prevention: Challenges and Opportunities.

IN BRIEF Addressing the problem of childhood obesity is an important component of preventing type 2 diabetes. Although children and their families ultimately make decisions about diet, physical activity, and obesity management, many groups have a role in making these choices easier. They do this by providing families with tools and resources and by implementing policies and practices that support a healthy diet and physical activity in the places where children and their families spend their time. Diabetes educators are an important part of the solution.

Bioaccumulation of Polychlorinated Biphenyls (PCBs) in Atlantic Sea Bream (Archosargus rhomboidalis) from Kingston Harbour, Jamaica.

Multiple sizes of Sea bream were collected from Kingston Harbour, Jamaica, to assess steady state bioaccumulation of polychlorinated biphenyls (PCBs) in a tropical fish. Sea beam fork lengths ranged from 7.3 to 21.5 cm (n = 36 fish) and tissue lipids decreased with body length. Larger fish had lower δ13C isotopes compared to smaller fish, suggesting a change in diet. Linear regressions showed no differences in lipid equivalent sum PCB concentrations with size. However, differences in individual congener bioaccumulation trajectories occurred. Less hydrophobic PCBs decreased with increasing body length, intermediate PCBs showed no trend, whereas highly hydrophobic (above log KOW of 6.5) PCBs increased. The different congener patterns were interpreted to be a result of decreases in overall diet PCB concentrations with increased fish length coupled with differences in PCB toxicokinetics as a function of hydrophobicity yielding dilution, pseudo-steady state and non-steady state bioaccumulation patterns.

Physical Inactivity Among Adults Aged 50 Years and Older - United States, 2014.

Physical activity can help delay, prevent, or manage many of the chronic diseases for which adults aged ≥50 years are at risk (1-3). These diseases can impact the length and quality of life, as well as the long-term ability to live independently.* All adults aged ≥50 years, with or without chronic disease, gain health benefits by avoiding inactivity (2,3). To examine the prevalence of inactivity by selected demographic characteristics and chronic disease status in mid-life and older adults, CDC analyzed data on adults aged ≥50 years from the 2014 Behavioral Risk Factor Surveillance System (BRFSS). Overall, 27.5% of adults aged ≥50 years reported no physical activity outside of work during the past month. Inactivity prevalence significantly increased with increasing age and was 25.4% among adults aged 50-64 years, 26.9% among those aged 65-74 years, and 35.3% among those aged ≥75 years. Inactivity prevalence was significantly higher among women than men, among Hispanics and non-Hispanic blacks than among non-Hispanic whites, and among adults who reported ever having one or more of seven selected chronic diseases than among those not reporting one. Inactivity prevalence significantly increased with decreasing levels of education and increasing body mass index. To help adults with and without chronic disease start or maintain an active lifestyle, communities can implement evidence-based strategies, such as creating or enhancing access to places for physical activity, designing communities and streets to encourage physical activity, and offering programs that address specific barriers to physical activity.

Staged imaging pathway for the evaluation of pediatric appendicitis.

PURPOSE: Despite significant radiation exposure involved with computed tomography (CT) in evaluation of pediatric appendicitis, its use is still widespread. The goal of this study was to assess the effect of a staged imaging pathway for appendicitis to significantly decrease CT use while maintaining diagnostic accuracy. METHODS: Chart review was performed for patients evaluated for appendicitis over a 12-month period prior to and after pathway implementation. RESULTS: There was a significant decrease in CT use as initial imaging after implementation of the pathway; 87.1-13.4 % for evaluations positive for appendicitis (decrease 84.6 %, p < 0.0001) and 82.6-9.2 % for evaluations negative for appendicitis (decrease 88.9 %, p < 0.0001). Use of CT during any point in the evaluation decreased from 91.7 to 25.1 % (decrease 72.6 %, p < 0.0001). The negative appendectomy rate was similar; 5.4 % prior, 4.9 % post (p = 0.955). The missed appendicitis rate did not statistically change; 1.1 % prior, 3.7 % post (p = 0.523). The perforation rate was not statistically altered; 6.5 % prior; 9.8 % post (p = 0.421). 350 less patients underwent CT during the year following the pathway. CONCLUSIONS: The staged imaging pathway resulted in a marked decrease in children exposed to CT without compromising diagnostic accuracy.

Toward Achieving Health Equity: Emerging Evidence and Program Practice.

Health equity, in the context of public health in the United States, can be characterized as action to ensure all population groups living within a targeted jurisdiction have access to the resources that promote and protect health. There appear to be several elements in program design that enhance health equity. These design elements include consideration of sociodemographic characteristics, understanding the evidence base for reducing health disparities, leveraging multisectoral collaboration, using clustered interventions, engaging communities, and conducting rigorous planning and evaluation. This article describes selected examples of public health programs the Centers for Disease Control and Prevention (CDC) has supported related to these design elements. In addition, it describes an initiative to ensure that CDC extramural grant programs incorporate program strategies to advance health equity, and examples of national reports published by the CDC related to health disparities, health equity, and social determinants of health.

Role of renin angiotensin system inhibitors and metformin in Glioblastoma Therapy: a review.

Glioblastoma multiforme (GBM) is a highly aggressive and incurable disease accounting for about 10,000 deaths in the USA each year. Despite the current treatment approach which includes surgery with chemotherapy and radiation therapy, there remains a high prevalence of recurrence. Notable improvements have been observed in persons receiving concurrent antihypertensive drugs such as renin angiotensin inhibitors (RAS) or the antidiabetic drug metformin with standard therapy. Anti-tumoral effects of RAS inhibitors and metformin have been observed in in vitro and in vivo studies. Although clinical trials have shown mixed results, the potential for the use of RAS inhibitors and metformin as adjuvant GBM therapy remains promising. Nevertheless, evidence suggest that these drugs exert multimodal antitumor actions; by particularly targeting several cancer hallmarks. In this review, we highlight the results of clinical studies using multidrug cocktails containing RAS inhibitors and or metformin added to standard therapy for GBM. In addition, we highlight the possible molecular mechanisms by which these repurposed drugs with an excellent safety profile might elicit their anti-tumoral effects. RAS inhibition elicits anti-inflammatory, anti-angiogenic, and immune sensitivity effects in GBM. However, metformin promotes anti-migratory, anti-proliferative and pro-apoptotic effects mainly through the activation of AMP-activated protein kinase. Also, we discussed metformin's potential in targeting both GBM cells as well as GBM associated-stem cells. Finally, we summarize a few drug interactions that may cause an additive or antagonistic effect that may lead to adverse effects and influence treatment outcome.

Use of an emergency preparedness disaster simulation with undergraduate nursing students.

This is a report of an educational strategy to prepare nursing students to respond to disasters. The strategy includes an emergency preparedness disaster simulation (EPDS) implemented in a school of nursing simulation lab using patient simulators, task trainer mannequins, and live actors. The EPDS immerses student groups into a "tornado ravaged assisted-living facility" where the principles of emergency preparedness can be employed. A total of 90 B.S.N. students participated in the EPDS in the final semester of their senior year. Student post-simulation survey responses were overwhelmingly positive, with mean scores of 4.65 (on a 5-point Likert scale) reported for the EPDS "increasing understanding of emergency preparedness" and "well organized." Mean scores were over 4.40 for "scenario believability, increasing knowledge base, increasing confidence in working in teams, ability to handle emergency preparedness situations and to work more effectively in hospital or clinic." The lowest mean score of 4.04 was for "prompting realistic expectations." Owing to the effectiveness of this educational strategy, the EPDS has been incorporated into the undergraduate curriculum.

A review of primary care referrals for patients with dizziness and vertigo: prevalence and demographics.

BACKGROUND: International studies show that dizziness and vertigo are a significant burden on the general population, with 20-30% experiencing symptoms over a lifetime. There are no Irish studies indicating prevalence. The aim of this study was to review primary care referrals for patients with dizziness and vertigo to an otolaryngology tertiary centre. METHODS: A review of an out-patient department waiting list was performed on primary care referrals for dizziness and vertigo to an otolaryngology tertiary centre. Demographic information was recorded on all patients referred between May 2017 and August 2019. RESULTS: Two hundred fifteen patients out of 901 patients (24%) referred to an otologist between May 2017 and August 2019 were referred with dizziness as a presenting complaint. The average age was 51 years. F/M ratio was 3:2. The average waiting time was 441 days. The most common associated otological symptom was tinnitus (42%). Relevant comorbidities included anxiety, depression, migraine/headaches and cardiac disease. CONCLUSION: This study demonstrates that a significant number of patients referred to an otologist from primary care are referred with dizziness and vertigo and supports the need for the establishment of multi-disciplinary vestibular/balance centres to address and manage these patients.

Roles of Angiotensin III in the brain and periphery.

Angiotensin (Ang) III, a biologically active peptide of the renin angiotensin system (RAS) is predominantly known for its central effects on blood pressure. Our understanding of the RAS has evolved from the simplified, classical RAS, a hormonal system regulating blood pressure to a complex system affecting numerous biological processes. Ang II, the main RAS peptide has been widely studied, and its deleterious effects when overexpressed is well-documented. However, other components of the RAS such as Ang III are not well studied. This review examines the molecular and biological actions of Ang III and provides insight into Ang III's potential role in metabolic diseases.

Impact of 40 Hz Transcranial Alternating Current Stimulation on Cerebral Tau Burden in Patients with Alzheimer's Disease: A Case Series.

BACKGROUND: Alzheimer's disease (AD) is characterized by diffuse amyloid-ß (Aß) and phosphorylated Tau (p-Tau) aggregates as well as neuroinflammation. Exogenously-induced 40 Hz gamma oscillations have been showing to reduce Aß and p-Tau deposition presumably via microglia activation in AD mouse models. OBJECTIVE: We aimed to translate preclinical data on gamma-induction in AD patients by means of transcranial alternating current stimulation (tACS). METHODS: Four participants with mild-to-moderate AD received 1 h of daily 40 Hz (gamma) tACS for 4 weeks (Monday to Friday) targeting the bitemporal lobes (20 h treatment duration). Participant underwent Aß, p-Tau, and microglia PET imaging with [11C]-PiB, [18F]-FTP, and [11C]-PBR28 respectively, before and after the intervention along with electrophysiological assessment. RESULTS: No adverse events were reported, and an increase in gamma spectral power on EEG was observed after the treatment. [18F]-FTP PET revealed a significant decrease over 2% of p-Tau burden in 3/4 patients following the tACS treatment, primarily involving the temporal lobe regions targeted by tACS and especially mesial regions (e.g., entorhinal cortex). The amount of intracerebral Aß as measured by [11C]-PiB was not significantly influenced by tACS, whereas 1/4 reported a significant decrease of microglia activation as measured by [11C]-PBR28. CONCLUSION: tACS seems to represent a safe and feasible option for gamma induction in AD patients, with preliminary evidence of a possible effect on protein clearance partially mimicking what is observed in animal models. Longer interventions and placebo control conditions are needed to fully evaluate the potential for tACS to slow disease progression.

Multi-modality human phenotyping to examine subjective and objective health afflictions in former professional American-style football players: The In-Person Assessment (IPA) protocol.

BACKGROUND: Participation in American-style football (ASF), one of the most popular sports worldwide, has been associated with adverse health outcomes. However, prior clinical studies of former ASF players have been limited by reliance on subjective self-reported data, inadequate sample size, or focus on a single disease process in isolation. OBJECTIVE: To determine the burden of objective multi-system pathology and its relationship with subjective health complaints among former professional ASF players. METHODS: The In-Person Assessment is a case-control, multi-day, deep human phenotyping protocol designed to characterize and quantify pathology among former professional ASF players. Participants, recruited from an on-going large-scale longitudinal cohort study, will include 120 men who report either no health conditions, a single health condition, or multiple health conditions across the key domains of cardiometabolic disease, disordered sleep, chronic pain, and cognitive impairment. Data will be collected from validated questionnaires, structured interviews, physical examinations, multi-modality imaging, and functional assessments over a 3-day study period. A pilot study was conducted to assess feasibility and to obtain participant feedback which was used to shape the final protocol. RESULTS: This study provides a comprehensive assessment of objective multi-system pathology and its relationship with subjective health complaints among former professional ASF players. CONCLUSION: The study will determine whether subjective health complaints among former professional ASF players are explained by objective explanatory pathology and will provide novel opportunities to examine the interrelatedness of co-morbidities. It is anticipated that this protocol will be applicable to other clinical and occupational populations.