Coverage of education and training of traumatic brain injury-induced growth hormone deficiency in US residency and fellowship programs: a cross-sectional study.

BACKGROUND: Hypopituitarism, including growth hormone deficiency (GHD), is a common sequela of traumatic brain injury (TBI). This study explored the coverage of education and training of TBI-induced hypopituitarism in general and GHD in particular, in postgraduate program curricula to identify knowledge gaps and opportunities. METHODS: An online survey and qualitative interviews (focus groups) were conducted among endocrinology, neurology, and physiatry postgraduate program directors in the United States (US). The study received an IRB exemption. RESULTS: A total of 419 fellowship and residency programs were invited to participate; 60 program directors completed the survey and 11 of these participated in the focus groups. About half of the respondents considered TBI-induced hypopituitarism important or fairly important to include in the curriculum, and nearly two-thirds considered it an appropriate training component. Neurology program directors considered education regarding hypopituitarism following TBI less important and relevant for their curricula compared with endocrinology and physiatry program directors. About half (53%) of the programs responded that they included TBI-induced pituitary disorders in their curricula. About two-thirds (68%) of endocrinology programs, compared with only one-quarter (25%) of neurology programs, covered TBI-induced pituitary disorders. Respondents identified multiple barriers to expanding hypopituitarism following TBI in the curriculum, including the rarity of condition and lack of time/room in the curriculum. Respondents reported that consensus clinical guidelines and the availability of more data on TBI-induced hypopituitarism, including GHD, would greatly impact the development of educational curricula on this topic. CONCLUSIONS: To improve the management of TBI-induced hypopituitarism, education and training should be expanded in US fellowship and residency programs to prepare trainees to effectively screen, diagnose, and treat TBI-induced hypopituitarism, including GHD.

A traumatic brain injury (TBI) can occur with a sudden blow to the head or the body. Most people recover from TBI within weeks, but the injury can cause long-term effects by reducing the body's production of growth hormone (GH), which can interfere with daily activities and impair quality of life. This study explored education and training of doctors in the US to identify gaps in knowledge about GH deficiency and opportunities for improvement. Online survey and interviews (focus groups) were conducted among directors of 3 postgraduate (after medical school) training programs: endocrinology, neurology, and physiatry (the diagnosis, prevention, and treatment of all types of impairment related to the brain, nerves, bones, and muscles).A total of 60 program directors completed the survey and 11 of these participated in the focus groups. About half of the respondents felt education about GH deficiency caused by TBI is important, and nearly two-thirds thought it was appropriate to include in medical training. Half of the programs said that hormone disorders caused by TBI were currently included in their training. Respondents identified multiple barriers to expanding education on this topic in training programs. The main barriers were that the condition is thought to be uncommon and not having time for more training. Respondents thought that clinical guidelines and availability of more information on the condition would greatly impact the development of training about GH deficiency after TBI.To improve the management of GH deficiency caused by TBI, education and training should be expanded to prepare doctors in training to be better able to screen, diagnose, and treat GH deficiency caused by TBI.

The National Football League Concussion Protocol: A Review.

Sport-related concussion remains an area of high concern for contact sport athletes and their families, as well as for the medical and scientific communities. The National Football League (NFL), along with the NFL Players Association and experts in the field, has developed protocols for the detection and management of sport-related concussions. This article reviews the NFL's most recent concussion protocol including preseason education and baseline testing for players, concussion surveillance by gameday medical teams and neurotrauma consultants and athletic trainers, gameday concussion protocol and procedures, and return to participation guidelines.

Comparison of Four Methods of RNA Extraction and cDNA Synthesis from The Venom of Peruvian Snakes of the Genus Bothrops of Clinical Importance.

RNA purification and cDNA synthesis represents the starting point for molecular analyses of snake venom proteins-enzymes. Usually, the sacrifice of snakes is necessary for venom gland extraction to identify protein-coding transcripts; however, the venom can be used as a source of transcripts. Although there are methods for obtaining RNA from venom, no comparative analysis has been conducted in the Bothrops genus. In the present study, we compared four commercial methods for RNA purification and cDNA synthesis from venom (liquid, lyophilized, or long-term storage) of four clinically relevant species of Peruvian Bothrops. Our results show that the TRIzol method presents the highest yield of RNA purified from venom (59 ± 11 ng/100 µL or 10 mg). The SuperScript First-Strand Synthesis System kit produced high amounts of cDNA (3.2 ± 1.2 ng cDNA/ng RNA), and the highest value was from combination with the Dynabeads mRNA DIRECT kit (4.8 ± 2.0 ng cDNA/ng RNA). The utility of cDNA was demonstrated with the amplification of six relevant toxins: thrombin-like enzymes, P-I and P-III metalloproteinases, acid and basic phospholipases A2, and disintegrins. To our knowledge, this is the first comparative study of RNA purification and cDNA synthesis methodologies from Bothrops genus venom.

Growth Hormone Deficiency Following Traumatic Brain Injury in Pediatric and Adolescent Patients: Presentation, Treatment, and Challenges of Transitioning from Pediatric to Adult Services.

Abstract Traumatic brain injury (TBI) is increasingly recognized, with an incidence of approximately 110 per 100,000 in pediatric populations and 618 per 100,000 in adolescent and adult populations. TBI often leads to cognitive, behavioral, and physical consequences, including endocrinopathies. Deficiencies in anterior pituitary hormones (e.g., adrenocorticotropic hormone, thyroid-stimulating hormone, gonadotropins, and growth hormone [GH]) can negatively impact health outcomes and quality of life post-TBI. This review focuses on GH deficiency (GHD), the most common post-TBI pituitary hormone deficiency. GHD is associated with abnormal body composition, lipid metabolism, bone mineral density, executive brain functions, behavior, and height outcomes in pediatric, adolescent, and transition-age patients. Despite its relatively frequent occurrence, post-TBI GHD has not been well studied in these patients; hence, diagnostic and treatment recommendations are limited. Here, we examine the occurrence and diagnosis of TBI, retrospectively analyze post-TBI hypopituitarism and GHD prevalence rates in pediatric and adolescent patients, and discuss appropriate GHD testing strategies and GH dosage recommendations for these patients. We place particular emphasis on the ways in which testing and dosage recommendations may change during the transition phase. We conclude with a review of the challenges faced by transition-age patients and how these may be addressed to improve access to adequate healthcare. Little information is currently available to help guide patients with TBI and GHD through the transition phase and there is a risk of interrupted care; therefore, a strength of this review is its emphasis on this critical period in a patient's healthcare journey.

Return to Full Participation Following Concussion in the National Football League, 2015 Through 2020.

OBJECTIVE: Quantify days missed, games missed, injury burden, and time to return to full participation (RTFP) among National Football League (NFL) players who sustained a concussion. DESIGN: Retrospective cohort study. SETTING: 2015 through 2020 NFL seasons. PARTICIPANTS: National Football League players diagnosed with a concussion from 2015 to 2020. INTERVENTIONS: National Football League-mandated graduated RTFP protocol. MAIN OUTCOME MEASURES: Days missed, games missed, burden, and time to RTFP, overall and by position. RESULTS: An annual average of 3639 player-days of participation and 255 games were missed across NFL because of concussion. Concussed players missed a median of 9 days (mean = 15.0), a relatively stable metric over 6 years, with slight variation by position. Offensive linemen, tight ends, running backs, and linebackers missed the most days per concussion; defensive secondary, offensive linemen, and wide receivers sustained the highest injury burden. Postconcussion, 59% of players missed one or more scheduled games. Among players concussed in a Sunday game, 38% played in a Sunday game one week later. CONCLUSIONS: The 9-day median time missed post-concussion may be related to emphasis on graduated phase-based concussion management. No concussed player returned to competition on the day of injury, and less than 40% participated in games the following week. Further work is needed to better understand characteristics of concussions that take longer to return and movement through stages of return.

Biological and proteomic characterization of the venom from Peruvian Andes rattlesnake Crotalus durissus.

The Peruvian rattlesnake Crotalus durissus is a venomous species that is restricted to the Peruvian Departments of Puno and Madre de Dios. Although clinically meaningful in this region, Crotalus durissus venom composition remains largely elusive. In this sense, this work aimed to provide a primary description of Peruvian C. durissus venom (PCdV). The enzymatic activities (SVMP, SVSP, LAAO, Hyaluronidase and PLA2) of PCdV were analyzed and compared to Brazilian Crotalus durissus terrificus venom (BCdtV). PCdV showed higher PLA2 activity when compared to the Brazilian venom. PCdV also showed cytotoxicity in VERO cells. For proteomic analysis, PCdV proteins were separated by HPLC, followed by SDS-PAGE. Gel bands were excised and tryptic digested for MALDI-TOF/TOF identification. Approximately 21 proteins were identified, belonging to 7 families. Phospholipases A2 (PLA2, 66.63%) were the most abundant proteins of the venom, followed by snake venom serine proteinases (SVSPs, 13.37%), C-type lectins (Snaclec, 8.98%) and snake venom metalloproteinases (SVMPs, 7.13%), crotamine (2.98%) and phosphodiesterase (PDE, 0.87%). Moreover, antivenom recognition assays indicated that both Brazilian and Peruvian antivenoms recognize PCdV, indicating the presence of antigenically related proteins in crotalic venoms. The results reported here, may impact in the venom selection for the production of effective Pan-American crotalic antivenom.

Epidemiology of Concussion in the National Football League, 2015-2019.

BACKGROUND: Concussion in American football, and specifically the National Football League (NFL) is a major area of interest and key focus for injury prevention. Complete and accurate characterization of when, how, and to whom these injuries occur can facilitate injury reduction efforts. Existing studies of concussion in the NFL use publicly available data, potentially limiting data quality and the inferences that can be made. HYPOTHESIS: Concussion incidence in the NFL decreased across the 2015-2019 seasons. STUDY DESIGN: Descriptive epidemiology study. LEVEL OF EVIDENCE: Level 4. METHODS: Concussion incidence, including counts, one-season risk, and rates per game and player-plays, among active NFL players from 2015 to 2019 is described by year, season, play type, and roster position. RESULTS: A total 1302 concussions were identified from 2015 to 2019 among 1004 players. Of these, 80% occurred in NFL games. The average annual incidence of in-season game concussions changed over the study period, from 230.7 per season (2015-2017) to 177.0 per season (2018-2019); this represented a 23% decrease in game settings (P < 0.01). Practice concussions fluctuated across the years of the study from 38 to 67 per season (average = 50.8/season). There were 70.6 concussions per 100 preseason games, which was slightly higher than the regular season rate per game of 61.7. Overall, there were 790 regular season game concussions across 4,657,243 player-plays and 114,428 player-games during the 5-year study. In regular season games, the majority of concussions were sustained on running and passing plays (n = 119/season), and the highest average rate per play occurred on kickoffs (0.69/100 plays). Defensive secondary (cornerbacks, safeties, and generic defensive backs) and offensive line incurred the most concussions, and the highest rates of concussion were among tight ends and wide receivers. CONCLUSION AND RELEVANCE: Concussions in the NFL are a key focus for player safety. Concussion reduction strategies were implemented before 2018, after which there was a sustained 2-year decrease in concussion incidence, providing a new benchmark from which to work toward further injury reduction.

Behavioral and sociodemographic predictors of anxiety and depression in patients under epidemiological surveillance for COVID-19 in Ecuador.

Ecuador has been one of the most affected countries by the Corona Virus Disease 19 (COVID-19) pandemic, by April 2020 this country presented the highest rates of mortality in Latin America. The purpose of the present study was to identify behaviors during confinement and sociodemographic variables associated with the mental health status of confirmed or suspected COVID-19 patients who were part of the epidemiological surveillance program in Ecuador that included mandatory confinement and self-isolation. A cross-sectional study was performed from March 22th to April 18th, 2020 using an online survey. The survey collected socio-demographic information and severity of depressive symptoms using the Patient Health Questionnaire-9 and anxiety symptoms through the Generalized Anxiety Disorder-7. A total of 759 patients completed the questionnaire, 20.3% presented moderate to severe symptoms of depression and 22.5% moderate to severe symptoms of anxiety. Being a woman and from the Coastal region were risk factors. Exercising, maintaining daily routines, and keeping informed about the COVID-19 but limiting to an hour was associated with better mental health. Regression analysis indicated that the mentioned behaviors explained approximately 17% of the variance for depression sum scores and 11.8% of the variance for anxiety sum scores while controlling for gender and region. Understanding the association between sociodemographic variables and psychological states in patients with COVID-19 is relevant to tackle future public mental health problems and to implement health policies that are intended to palliate further psychiatric complications. Promotion of modifiable behaviors such as exercising, maintaining daily routines, and keeping informed about the COVID-19 but limiting to less than an hour is recommended.

Proteomic and toxinological characterization of Peruvian pitviper Bothrops brazili ("jergón shushupe"), venom.

Bothrops brazili is a pitviper from Amazonian region, responsible for many accidents in Peru. Despite its relevance, its venom has not been extensively characterized. In the present work, Bothrops brazili venom (BbV) components were analyzed by RP-HPLC, SDS-PAGE and MALDI-TOF/TOF. Approximately 37 proteins were identified, belonging to 7 families. Snake venom metalloproteinases (SVMPs) were the most abundant proteins of the venom (33.05%), followed by snake venom serine proteinases (SVSPs, 26.11%), phospholipases A2 (PLA2, 25.57%), snake C-type lectins (CTLs, 9.61%), L-aminoacid oxidase (LAAO, 3.80%), cystein-rich secretory proteins (CRISP, 1.67%) and Bradykinin-potentiating peptide (BPP, 0.20%). In vitro enzymatic activities of BbV showed high levels of SVMP activity and reduced Hyal activity in comparison with other bothropic venoms. Furthermore, BbV reduced VERO cells viability. ELISA and Western Blotting showed that both Peruvian and Brazilian bothropic antivenoms were able to recognize BbV components. This work provides an overview of BbV venom content and indicates a potential efficiency of Peruvian and Brazilian antivenoms to treat accidents with this species.

Emergency Preparedness of Secondary School Athletic Programs in Arizona.

CONTEXT: Schools that sponsor athletic programs have an obligation to provide a safe environment with appropriate policies for addressing emergencies. OBJECTIVE: To describe the emergency preparedness of secondary schools in Arizona specific to emergency action plans (EAPs), cardiac arrest, concussion, and heat illness. DESIGN: Cross-sectional study. SETTING: Online survey. PATIENTS OR OTHER PARTICIPANTS: Athletic directors from 143 Arizona secondary schools (response rate = 54%). INTERVENTION(S): A 6-section survey that included questions related to athletic trainer (AT) access, EAPs, automated external defibrillators (AEDs), concussion, heat illness, and other policies. MAIN OUTCOME MEASURE(S): Descriptive statistics were reported. Comparisons of responses between schools with and without AT access were conducted with Mann-Whitney U tests. RESULTS: Most respondents (81%, n = 116) indicated their school had access to an AT, and 95% (n = 125) of respondents reported their school had a written EAP. The AEDs were available at most (93%, n = 121) schools. All respondents were familiar with the interscholastic concussion policy, and 98% (n = 123) indicated they had a school-specific policy. Almost all respondents (99%, n = 121) reported being familiar with the state heat-illness policy. Environmental measures were taken before practices at 48% (n = 60) of schools. Schools with access to an AT were more likely to have an EAP, venue-specific EAPs, physician approval of EAPs, AEDs, heat-illness policies, and cold-water immersion tubs and to take environmental measures. CONCLUSIONS: Whereas the majority of schools reported AT access, not all schools had adequate EAPs in place. Schools would benefit from educational opportunities regarding best practices and policy development to improve emergency preparedness.

Características de neumonía por Covid-19 en tc de tórax: revisión de la literatura actual / Features of Covid-19 pneumonia in chest ct: current literature review

INTRODUCCIÓN: Desde diciembre de 2019 la neumonía por SARS-CoV-2 ha experimentado un fuerte avance presentando a la fecha más de nueve millones de casos a nivel mundial. El objetivo de esta revisión es describir las principales características de la neumonía por COVID-19 en la tomografía computada (TC) de tórax en pacientes adultos. MATERIALES Y MÉTODOS: Se buscaron en PubMed artículos que se centraran en las características de la infección por COVID-19 en la tomografía computada de tórax en adultos durante el último año, en inglés y español. Las palabras clave fueron: "COVID-19", "chest CT manifestations" "chest CT findings" y "chest CT features", excluyendo estudios en población pediátrica, cartas al editor y casos clínicos. Se examinaron títulos y resúmenes de artículos obtenidos y se descartaron estudios no atingentes al objetivo de la investigación. RESULTADOS: Se obtuvieron 21 artículos. Una gran variedad de hallazgos en la TC de tórax han sido reportados en los distintos artículos revisados, siendo los más característicos las opacidades en "vidrio esmerilado" de predominio periférico y bilateral; con o sin consolidaciones, que además pueden asociarse a engrosamiento septal interlobulillar, conformando un patrón en empedrado (crazy paving) y a engrosamiento perivascular. Menos frecuentes son el compromiso central, la presencia de nódulos, quistes y derrame pleural. CONCLUSIONES: La tomografía computada de tórax tiene un papel fundamental en la evaluación y manejo de los pacientes con COVID-19, con un evidente rol diagnóstico en ciertas situaciones. El conocimiento de sus características imagenológicas resulta de suma importancia en el contexto actual

Introduction: The new Coronavirus Disease 2019 (COVID-19) has become an unprecedented global health emergency. The World Health Organization estimates global mortality from COVID-19 at 3.4%, however it will be higher in patients with comorbidities such as Cancer (5.6%), High Blood Pressure (6.0%), Chronic respiratory disease (6.3%), Diabetes (7.3%) and Cardiovascular Disease (10.5%). These diseases are among the most prevalent in the world, for this reason we pretend to synthesize their pathophysiology and role in COVID-19, in order to identify effective measures that decrease morbidity and mortality in these high risk groups. Methodology: A review was performed using the databases MEDLINE, PubMed and Google Scholar. Original articles and bibliographic review articles were considered, prioritizing the articles published this year. Results: SARS-CoV-2 uses the enzyme ACE2 as a functional receptor, which allows its entry into the host cell. Eventually, regulates its expression downward, with Angiotensin-II prevailing with its profibrotic, prothrombotic and proinflammatory functions, leading to the deleterious effects of the disease. Chronic non-transmissible diseases (NTCD) would have baseline alteration in ACE2 levels, dysregulation of the immune system, endothelial dysfunction, and chronic inflammation, which would be associated with increased susceptibility and severity in COVID-19. Conclusion: Prevention and identification of risk patients remains the main measure against COVID-19. It is necessary to emphasize efforts in the prevention of NTCD and the promotion of healthy lifestyles. The negative effects of prolonged confinement and suspension of health care services must be considered.

Estimation of daily milk yield of Nellore cows grazing tropical pastures.

Beef cows' milk yield is typically determined by measuring milk yield once daily and then doubling this value to estimate daily production. However, it is not known whether this is accurate. Thus, we aimed to determine the association between morning and afternoon milk yield in grazing Nellore cows. Eighty Nellore cows were used, with initial weight of 516.0 ± 1.0 kg. The experiment was a completely randomized factorial scheme, with 20 replications and four treatments (i.e., + or - pre-partum supplementation in combination with + or - post-partum supplementation): PRMM-1 kg of supplement/cow/day for 90 days pre-partum; MMPS-1 kg of supplement/cow/day for 90 days post-partum; PRPS-1 kg of supplement/cow/day for 90 days pre-partum and 90 days post-partum; and MM-only mineral mix ad libitum during pre- and post-partum. Milk was sampled on days 45, 135, and 225 post-partum (early, middle, and late lactation, respectively). No effects were observed of pre- and post-partum supplementation on milk yield (P > 0.05). The afternoon/morning proportion of 0.45 in the early third of lactation was higher than other stages, which had a proportion of 0.41 (P < 0.05). Post-partum supplementation increased milk protein in the morning and afternoon milking (P < 0.05). There was also no effect of pre- and post-partum supplementation on afternoon-morning proportion other milk components (P > 0.05). We conclude that estimating daily milk production of grazing beef cattle by multiplying a once daily milking amount times two is not accurate. Under the conditions of this study, proportion of total daily production represented by the ratio of afternoon/morning milking was 0.45 in early lactation (first third) and 0.41 in mid- and late lactation.

National Football League Head, Neck and Spine Committee's Concussion Diagnosis and Management Protocol: 2017-18 season.

One of the National Football League's (NFL) Head, Neck and Spine Committee's principal goals is to create a 'best practice' protocol for concussion diagnosis and management for its players. The science related to concussion diagnosis and management continues to evolve, thus the protocol has evolved contemporaneously. The Fifth International Conference on Concussion in Sport was held in Berlin in 2016, and guidelines for sports concussion diagnosis and management were revised and refined. The NFL Head, Neck and Spine Committee has synthesised the most recent empirical evidence for sports concussion diagnosis and management including the Berlin consensus statement and tailored it to the game played in the NFL. One of the goals of the Committee is to provide a standardised, reliable, efficient and evidence-based protocol for concussion diagnosis and management that can be applied in this professional sport during practice and game day. In this article, the end-of-season version of the 2017-18 NFL Concussion Diagnosis and Management Protocol is described along with its clinical rationale. Immediate actions for concussion programme enhancement and research are reviewed. It is the Committee's expectation that the protocol will undergo refinement and revision over time as the science and clinical practice related to concussion in sports crystallise.

A coupled in vitro/in vivo approach for engineering a heterologous type III PKS to enhance polyketide biosynthesis in Saccharomyces cerevisiae.

Polyketides are attractive compounds for uses ranging from biorenewable chemical precursors to high-value therapeutics. In many cases, synthesis in a heterologous host is required to produce these compounds in industrially relevant quantities. The type III polyketide synthase 2-pyrone synthase (2-PS) from Gerbera hybrida was used for the production of triacetic acid lactone (TAL) in Saccharomyces cerevisiae. Initial in vitro characterization of 2-PS led to the identification of active site variants with improved kinetic properties relative to wildtype. Further in vivo evaluation in S. cerevisiae suggested certain 2-PS mutations altered enzyme stability during fermentation. In vivo experiments also revealed beneficial cysteine to serine mutations that were not initially explored due to their distance from the active site of 2-PS, leading to the design of additional 2-PS enzymes. While these variants showed varying catalytic efficiencies in vitro, they exhibited up to 2.5-fold increases in TAL production when expressed in S. cerevisiae. Coupling of the 2-PS variant [C35S,C372S] to an engineered S. cerevisiae strain led to over 10 g/L TAL at 38% of theoretical yield following fed-batch fermentation, the highest reported to date. Our studies demonstrate the success of a coupled in vitro/in vivo approach to engineering enzymes and provide insight on cysteine-rich enzymes and design principles toward their use in non-native microbial hosts.

Creep feeding effects on male Nellore calves influencing behavior and performance of their dams.

The objective of the present study was to evaluate the effect of different schemes of calves' supplementation in a creep feeding system, on the behavior of Bos indicus calves and dams, and also the influence of the calves' supplementation on dams' performance. Forty-eight Nellore male calves (147 ± 7 kg body weight and 3 months of age) in the suckling phase and their dams (476 ± 9 kg and 6 years of age) were studied in a completely randomized design. The experiment was divided into two periods of 71 days. The treatments were 5- and 10-g supplement dry matter (DM)/kg BW day offered in periods 1 and 2, respectively (5S/10S); 10- and 5-g supplement DM/kg BW day offered in periods 1 and 2, respectively (10S/5S); 7.5-g supplement DM/kg BW day in both periods 1 and 2 (7.5S); and mineral mix ad libitum in both periods 1 and 2 (MM). No differences (P < 0.05) in body condition score (BCS), final body weight (FBW), and average daily gain (ADG) were found in dams' performance. Calves from MM treatment spent more time (P < 0.05) grazing than the supplemented calves from 5S/10S and 10S/5S treatments, in the first period. No difference in suckling time was found between the treatments (P > 0.05) in the first evaluated period. Calves from 10S/5S treatment spent more time suckling and less time eating supplements (P < 0.05) than 5S/10S treatment animals, in the second evaluated period. Dams of MM treatment's calves had more idle time and lower grazing time when compared with the mothers of calves from 5S/10S and 10S/5S treatments. It was concluded that different schedules of Nellore calves' supplementation on pasture do not affect their mothers' performance, and supplementation decreases the grazing time of calves in the suckling phase.

Traumatic Brain Injury in Domestic Violence Victims: A Retrospective Study at the Barrow Neurological Institute.

Domestic violence is a national health crisis, which affects people of all ages, races, and socioeconomic classes. Traumatic brain injury is common in victims because of the high frequency of head and neck injuries inflicted through abuse. These recurrent injuries can lead to chronic symptoms with high morbidity. We conducted a retrospective chart review of 115 patients with a history of head trauma as a result of domestic violence. All patients were seen in a subspecialty traumatic brain injury clinic, at which time information regarding their histories and self-reported symptoms were recorded. In total, 109 females and 6 males were included in our study, with an age range of 4-68 years. Overall, 88% reported more than one injury and 81% reported a history of loss of consciousness associated with their injuries. Only 21% sought medical help at the time of injury. Whereas 85% had a history of abuse in adulthood, 22% had experienced abuse in both childhood and adulthood, and 60% of the patients abused as children went on to be abused as adults. Headache was the most common chief complaint, but on a self-reported symptom severity scale, behavioral symptoms were the most severe. Psychiatric disease was present in 84% of patients. Traumatic brain injury is a frequent sequela of domestic violence, from which many victims sustain multiple injuries without seeking medical care. Brain injuries are often sustained over many years and lead to lasting physical, behavioral, and cognitive consequences. Better understanding of these injuries will lead to improved care for this population.

Statements of Agreement From the Targeted Evaluation and Active Management (TEAM) Approaches to Treating Concussion Meeting Held in Pittsburgh, October 15-16, 2015.

BACKGROUND: Conventional management for concussion involves prescribed rest and progressive return to activity. Recent evidence challenges this notion and suggests that active approaches may be effective for some patients. Previous concussion consensus statements provide limited guidance regarding active treatment. OBJECTIVE: To describe the current landscape of treatment for concussion and to provide summary agreements related to treatment to assist clinicians in the treatment of concussion. METHODS: On October 14 to 16, 2015, the Targeted Evaluation and Active Management (TEAM) Approaches to Treating Concussion meeting was convened in Pittsburgh, Pennsylvania. Thirty-seven concussion experts from neuropsychology, neurology, neurosurgery, sports medicine, physical medicine and rehabilitation, physical therapy, athletic training, and research and 12 individuals representing sport, military, and public health organizations attended the meeting. The 37 experts indicated their agreement on a series of statements using an audience response system clicker device. RESULTS: A total of 16 statements of agreement were supported covering (1) Summary of the Current Approach to Treating Concussion, (2) Heterogeneity and Evolving Clinical Profiles of Concussion, (3) TEAM Approach to Concussion Treatment: Specific Strategies, and (4) Future Directions: A Call to Research. Support (ie, response of agree or somewhat agree) for the statements ranged from to 97% to 100%. CONCLUSION: Concussions are characterized by diverse symptoms and impairments and evolving clinical profiles; recovery varies on the basis of modifying factors, injury severity, and treatments. Active and targeted treatments may enhance recovery after concussion. Research is needed on concussion clinical profiles, biomarkers, and the effectiveness and timing of treatments. ABBREVIATIONS: ARS, audience response systemCDC, Centers for Disease Control and PreventionDoD, Department of DefensemTBI, mild traumatic brain injuryNCAA, National Collegiate Athletic AssociationNFL, National Football LeagueNIH, National Institutes of HealthRCT, randomized controlled trialRTP, return to playSRC, sport- and recreation-related concussionTBI, traumatic brain injuryTEAM, Targeted Evaluation and Active Management.

Engineering cofactor and transport mechanisms in Saccharomyces cerevisiae for enhanced acetyl-CoA and polyketide biosynthesis.

Synthesis of polyketides at high titer and yield is important for producing pharmaceuticals and biorenewable chemical precursors. In this work, we engineered cofactor and transport pathways in Saccharomyces cerevisiae to increase acetyl-CoA, an important polyketide building block. The highly regulated yeast pyruvate dehydrogenase bypass pathway was supplemented by overexpressing a modified Escherichia coli pyruvate dehydrogenase complex (PDHm) that accepts NADP(+) for acetyl-CoA production. After 24h of cultivation, a 3.7-fold increase in NADPH/NADP(+) ratio was observed relative to the base strain, and a 2.2-fold increase relative to introduction of the native E. coli PDH. Both E. coli pathways increased acetyl-CoA levels approximately 2-fold relative to the yeast base strain. Combining PDHm with a ZWF1 deletion to block the major yeast NADPH biosynthesis pathway resulted in a 12-fold NADPH boost and a 2.2-fold increase in acetyl-CoA. At 48h, only this coupled approach showed increased acetyl-CoA levels, 3.0-fold higher than that of the base strain. The impact on polyketide synthesis was evaluated in a S. cerevisiae strain expressing the Gerbera hybrida 2-pyrone synthase (2-PS) for the production of the polyketide triacetic acid lactone (TAL). Titers of TAL relative to the base strain improved only 30% with the native E. coli PDH, but 3.0-fold with PDHm and 4.4-fold with PDHm in the Δzwf1 strain. Carbon was further routed toward TAL production by reducing mitochondrial transport of pyruvate and acetyl-CoA; deletions in genes POR2, MPC2, PDA1, or YAT2 each increased titer 2-3-fold over the base strain (up to 0.8g/L), and in combination to 1.4g/L. Combining the two approaches (NADPH-generating acetyl-CoA pathway plus reduced metabolite flux into the mitochondria) resulted in a final TAL titer of 1.6g/L, a 6.4-fold increase over the non-engineered yeast strain, and 35% of theoretical yield (0.16g/g glucose), the highest reported to date. These biological driving forces present new avenues for improving high-yield production of acetyl-CoA derived compounds.