Combinatorial treatment rescues tumour-microenvironment-mediated attenuation of MALT1 inhibitors in B-cell lymphomas.

Activated B-cell-like diffuse large B-cell lymphomas (ABC-DLBCLs) are characterized by constitutive activation of nuclear factor κB driven by the B-cell receptor (BCR) and Toll-like receptor (TLR) pathways. However, BCR-pathway-targeted therapies have limited impact on DLBCLs. Here we used >1,100 DLBCL patient samples to determine immune and extracellular matrix cues in the lymphoid tumour microenvironment (Ly-TME) and built representative synthetic-hydrogel-based B-cell-lymphoma organoids accordingly. We demonstrate that Ly-TME cellular and biophysical factors amplify the BCR-MYD88-TLR9 multiprotein supercomplex and induce cooperative signalling pathways in ABC-DLBCL cells, which reduce the efficacy of compounds targeting the BCR pathway members Bruton tyrosine kinase and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1). Combinatorial inhibition of multiple aberrant signalling pathways induced higher antitumour efficacy in lymphoid organoids and implanted ABC-DLBCL patient tumours in vivo. Our studies define the complex crosstalk between malignant ABC-DLBCL cells and Ly-TME, and provide rational combinatorial therapies that rescue Ly-TME-mediated attenuation of treatment response to MALT1 inhibitors.

Unique Features of the US Department of Defense Multidisciplinary Concussion Clinics.

The US Department of Defense (DoD) and the Department of Veterans Affairs (VA) actively address care needs for a subset of service members (SMs) who experience prolonged symptoms and adverse sequelae interfering with their usual level of function after sustaining mild traumatic brain injury. The development of multidisciplinary concussion clinics and implementation of several reinforcing policies within the DoD and the VA address this unique patient population. A network known as the National Intrepid Center of Excellence and Intrepid Spirit Centers and the VA, primarily support these patients through intensive outpatient programs. The VA also has an inpatient program that utilizes specialized capabilities. The features unique to several of these centers are described in this article. While providing for similar patient care needs, each clinical setting implements unique evaluation and treatment modalities to target analogous goals of return to the highest functional level possible and develop life skills to enhance health, quality of life, and readiness to perform military duties. Currently, patient-reported outcomes are being collected.

Dietary Intake and Menstrual Health among Acrobatics and Tumbling NCAA Division I Student-Athletes.

OBJECTIVE: Acrobatics & Tumbling (A&T) is an emerging sport in the National Collegiate Athletic Association that lacks research regarding the dietary intake and health of A&T student-athletes (A&Tsa). This study assessed the dietary intake adequacy, estimated energy availability (EA), self-reported menstrual health, and body composition of A&Tsa. METHODS: Twenty-four female A&Tsa participated during week 8 of the preseason (11 top: Age= 20.1 ± 0.9 years; BMI= 22.1 ± 1.7 kg/m2; 13 base: Age= 19.5 ± 1.3 years; BMI= 26.2 ± 2.7 kg/m2). Total energy intake (TEI) and macronutrient intakes were assessed via a paper-based 3-day dietary recall. Resting Metabolic Rate [RMR = 500 + 22 * fat-free mass (FFM)] and energy availability [EA = (TEI - exercise energy expenditure)/FFM)] were estimated; and LEAF-Q assessed menstrual health. Body composition was measured using Dual-Energy X-Ray Absorptiometry. Macronutrient intakes and EA were compared to sports nutrition recommendations (carbohydrate: 6-10 g/kg; protein: 1.2-2.0 g/kg) and the Acceptable Macronutrient Distribution Range (carbohydrate: 45-65%; protein: 10-35%; fat: 20-35%). RESULTS: TEI was 1753 ± 467 kcal (top) and 1980 ± 473.8 kcal (base). A total of 20.8% of A&Tsa failed to meet RMR with TEI, with a higher prevalence in the top (-266 ± 219.2 kcal, n = 3) vs. base (-414.3 ± 534.4 kcal, n = 2) A&Tsa. Top and base A&Tsa had both low EA (28.8 ± 13.4 kcals·FFM-1; 23.8 ± 9.5 kcals·FFM-1) and inadequate carbohydrate intake averages (4.2 ± 1.3 g/kg; 3.5 ± 1.1 g/kg, p < 0.001), respectively. A total of 17% of A&Tsa reported secondary amenorrhea, with a higher prevalence in the top (27.3%, n = 3) vs. the base (7.7%, n = 1). CONCLUSION: TEI and carbohydrate intake of the majority of A&Tsa were below recommendations. Sports dietitians should encourage and educate A&Tsa about following an adequate diet that meets energy and sports-specific macronutrient needs.

Sleep, Diet Quality, and Lipid Profile Assessment in NCAA Division I Acrobatics and Tumbling Student-Athletes: A Cross-Sectional Study.

OBJECTIVE: Acrobatics and Tumbling (A&T), an emerging National Collegiate Athletics Association (NCAA) sport, involves athletes with rigorous training backgrounds, usually extending from youth through early adulthood. This study examines the sleep health, diet quality, and lipid profile of A&T athletes clustered by their performance position. METHODS: Forty-two A&T athletes, clustered as tops (n = 19; age = 19.6 ± 1.0 years; body mass index [BMI] = 22.3 ± 1.7 kg/m2) and bases (n = 23; age = 19.6 ± 1.3 years; BMI = 25.7 ± 2.5 kg/m2), completed preseason sleep and diet quality (Rapid Eating Assessment for Participants-Shortened [REAP-S]) surveys. Fasting blood samples were collected for lipid analysis. Body composition was assessed via dual-energy X-ray absorptiometry. RESULTS: Most athletes (71.4%; base n = 14, top n = 16) reported insufficient sleep (≤7 hours) and "good" sleep quality (90.4%, n = 38; base n = 18, top n = 20). Average REAP-S score was 29.24 ± 3.74. Approximately 31% (n = 13) displayed at least one undesirable lipid concentration according to medical guidelines for normal levels (total cholesterol [TC] < 200 mg/dL, triglycerides [TG] < 150 mg/dL, high-density lipoprotein cholesterol [HDL-C] > 40 mg/dL, low-density lipoprotein cholesterol [LDL-C] < 130 mg/dL). Approximately 20% exhibited elevated TC (top n = 4, base n = 4), 12.5% had elevated TG (base n = 5), 2.5% showed low HDL-C (base n = 1), and 10% presented elevated LDL-C (top n = 2, base n = 2). CONCLUSIONS: Most athletes experienced suboptimal sleep (≤7 hours/night) and 31% displayed at least one undesirable lipid concentration (elevated TC, TG, or LDL-C or reduced HDL-C). Tailoring interventions with sports dietitians is recommended, focused on increasing monounsaturated and polyunsaturated fat intake while reducing saturated fat consumption. These interventions could mitigate cardiovascular risks, improve recovery, and possibly enhance athletic performance.

US Department of Defense Warfighter Brain Health Initiative: Maximizing performance on and off the battlefield.

The US Department of Defense (DoD) recognizes the importance of warfighter brain health with the establishment of the Warfighter Brain Health Initiative and Strategy. For a warfighter, also known as a service member, to perform at their highest level, cognitive and physical capabilities must be optimized. This initiative addresses brain health, brain exposures, to include blast overpressure exposures from weapons and munitions, traumatic brain injury (TBI), and long-term or late effects of TBI. The DoD's pursuit of maximal strength hinges on the speed of decisions (neurocognitive) and detection of brain injury when it occurs. The strategy creates a framework for deliberate, prioritized, and rapid development of end-to-end solutions for warfighter brain health. Through this strategy, DoD is addressing the needs of our service members, their families, line leaders/commanders, and their communities at large. The implications of this initiative and strategy are noteworthy for practitioners because the DoD Warfighter Brain Health construct lends itself to nurse practitioner engagement in clinical practice, patient education, policy development, and emerging research.

Epidemiology of Cervical Muscle Strains in Collegiate and High School Football Athletes, 2011-2012 Through 2013-2014 Academic Years.

CONTEXT: Cervical muscle strains are an often-overlooked injury, with neck- and spine-related research typically focusing on spinal cord and vertebral injuries. OBJECTIVE: To examine the rates and distributions of cervical muscle strains in collegiate and high school football athletes. DESIGN: Descriptive epidemiology study. SETTING: Collegiate and high school football teams. PATIENTS OR OTHER PARTICIPANTS: The National Collegiate Athletic Association Injury Surveillance Program (NCAA-ISP) collected data from collegiate football athletes. The High School National Athletic Treatment, Injury and Outcomes Network (HS NATION) and High School Reporting Information Online (HS RIO) collected data from high school football athletes. Data from the 2011-2012 through 2013-2014 academic years were used. MAIN OUTCOME MEASURE(S): Athletic trainers collected injury and exposure data for football players. Injury counts, injury rates per 10 000 athlete-exposures (AEs), and injury rate ratios with 95% confidence intervals (CIs) were calculated. RESULTS: The NCAA-ISP reported 49 cervical muscle strains (rate = 0.96/10 000 AEs), of which 28 (57.1%) were TL (time loss; rate = 0.55/10 000 AEs). High School NATION reported 184 cervical muscle strains (rate = 1.66/10 000 AEs), of which 33 (17.9%) were TL injuries (rate = 0.30/10 000 AEs). The HS RIO, which collects only TL injuries, reported 120 TL cervical muscle strains (rate = 0.51/10 000 AEs). The overall injury rate was lower in the NCAA-ISP than in HS NATION (injury rate ratio = 0.58; 95% CI = 0.42, 0.79); when restricted to TL injuries, the overall injury rate was higher in the NCAA-ISP (injury rate ratio = 1.83; 95% CI = 1.11, 3.03). No differences were found when comparing TL injuries in HS RIO and the NCAA-ISP. Cervical muscle-strain rates were higher during competitions than during practices across all 3 surveillance systems for all injuries. Most cervical muscle strains were due to player contact (NCAA-ISP = 85.7%, HS NATION = 78.8%, HS RIO = 85.8%). CONCLUSIONS: The incidence of cervical muscle strains in football players was low compared with other injuries. Nonetheless, identifying and implementing interventions, particularly those aimed at reducing unsafe player contact, are essential to further decrease the risk of injury and associated adverse outcomes.