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Background: Testing and evaluating athletes is necessary and should include performance, body composition, and nutrition. The purpose of this study was to report assessments of dietary intake, V˙O2max, and body composition in D1 collegiate athletes and examine relationships between these assessments. Methods: Dietary intake was assessed with 3-day recalls and compared to recommendations, and body composition was assessed via bioelectrical impedance analysis (BIA) (n = 48). V˙O2max was evaluated using a graded exercise test (GXT) with a verification bout (n = 35). Reliability between “true” V˙O2max and verification was determined. Correlations and regressions were performed. Results: Energy, carbohydrate, and micronutrient intake was lower than recommendations. Mean V˙O2max was 47.3 and 47.4 mL·kg−1·min−1 for GXT and verification, respectively. While correlations were apparent among dietary intake, V˙O2max, and body composition, percent fat-free mass (%FFM) predicted 36% of V˙O2max. Conclusions: Collegiate athletes are not meeting energy and carbohydrate recommendations and exceed fat recommendations. Vitamin D and magnesium were low in all sports, and iron and calcium were low in females. V˙O2max ranged from 35.6 to 63.0 mL·kg−1·min−1, with females below average and males meeting typical values for their designated sport. Assessing D1 athletes can provide guidance for sports dietitians, coaches, and strength and conditioning specialists to track and monitor nutrition in athletes.

IntroductionPolice officers must perform various tasks in unpredictable work environments and potentially volatile situations. This study aimed to determine if cardiovascular fitness, body composition, and physical activity levels could predict performance in a Midwest Police Department’s Physical Readiness Assessment (PRA).MethodsResearchers collected data from thirty incumbent police officers (33.9 ± 8.3 years, female = 5). Anthropometric data included height, body mass, body fat percentage (BF%), fat-free mass (FFM), and maximal hand grip strength. The police officers also completed a physical activity rating (PA-R) scale to estimate maximal oxygen consumption (V˙O2max) and the International Physical Activity Questionnaire (IPAQ). Police officers then conducted their department’s PRA. Stepwise linear regression analyses were used to determine the relationship between predictor variables and PRA performance. Pearson’s product-moment correlations investigated relationships between anthropometric, physical fitness, and physical activity variables and PRA performance using SPSS (v.28). The significance level was set at p

Abstract Background Metabolic flexibility is the ability of skeletal muscle to adapt fuel utilization to the demand for fuel sources [carbohydrates (CHO) and fats (FAT)]. The purpose of this study was to explore muscle energy metabolism and metabolic flexibility under various conditions in sarcopenic (S) versus nonsarcopenic (NS) older adults. Methods Twenty‐two older adults aged 65 years or older were categorized as NS [n = 11; mean ± standard deviation (SD); age = 73.5 ± 6.0 years (males, n = 5; females, n = 6)] or S [n = 11; 81.2 ± 10.5 years (males, n = 6; females, n = 5) based on handgrip strength, body composition and physical performance. Indirect calorimetry was recorded before and after consumption of a high‐CHO meal and during aerobic and anaerobic exercise. Respiratory quotient (RQ), CHO and FAT oxidation were assessed. Venous blood samples were collected for glucose and insulin concentrations. Results At rest, compared with NS, S exhibited a 5–8% higher RQ at 0 (0.72 vs. 0.76) and 120 (0.77 vs. 0.82), 150 (0.76 vs. 0.80), and 180 min (0.74 vs. 0.80) (P = 0.002–0.025); 59–195% higher CHO oxidation at 0, 120, and 180 min (0.0004–0.002 vs. 0.001–0.002 g·min−1·kg‐1) (P = 0.010–0.047); and 20–31% lower FAT oxidation at 0, 15, and 90–180 min (0.0009–0.0022 vs. 0.0011–0.002 g·min−1·kg−1) (P = 0.004–0.038). Glucose levels were significantly elevated in S versus NS at 0, 60 and 75 min (144.64–202.78 vs. 107.70–134.20 mg·dL−1) but not insulin. During aerobic exercise, RQ was 5% greater (0.90 vs. 0.86) (P = 0.039), and FAT oxidation was 35% lower at 6–8 min (0.003 vs. 0.005 g·min−1·kg−1) (P = 0.033) in S versus NS. During anaerobic exercise, CHO oxidation was 31% greater in NS versus S at 60–80% time to exhaustion (0.011 vs. 0.007 g·min−1·kg−1) (P = 0.015). Per cent contribution to energy expenditure was greater in S for CHO but lower for FAT at 0 (CHO: 22% vs. 10%; FAT: 78% vs. 91%) and 120–180 min (CHO: 35–42% vs. 17–25%; FAT: 58–65% vs. 75%–84%) (P = 0.003–0.046) at rest and 6–8 min during aerobic exercise (CHO: 70% vs. 57%; FAT: 30% vs. 45%) (P = 0.046). Conclusions The data show differences in skeletal muscle energy metabolism and substrate utilization between S and NS at rest, transitioning from fasted to fed state, and during exercise. Compared with NS, S displayed a diminished ability to adapt fuel utilization in response to feeding and exercise, reflecting metabolic inflexibility. Impaired metabolic flexibility could be a mechanism underlying the losses of strength and physical function accompanying sarcopenia.

Porphyromonas gingivalis (Pg) is a periodontopathic pathogen that may affect MUC5AC‐related mucus hypersecretion along airway epithelial cells. Here, we attempted to establish whether Pg virulence factors (lipopolysaccharide, FimA fimbriae, gingipains) affect MUC5AC in immortalized and primary bronchial cells. We report that MUC5AC gene expression and protein levels are affected by Pg culture supernatant, but not by lipopolysaccharide or FimA fimbriae. Cells treated with either Pg single (Kgp or Rgp) or double (Kgp/Rgp) mutants had altered levels of MUC5AC gene expression and protein levels, and MUC5AC staining of double mutant‐treated mouse lung cells showed that MUC5AC protein levels were unaffected. Taken together, we propose that Pg gingipains may be the primary virulence factor that influences both MUC5AC gene expression and protein levels.

Coronavirus disease 2019 (COVID-19) pandemic has been attributed to SARS-CoV-2 (SARS2) and, consequently, SARS2 has evolved into multiple SARS2 variants driving subsequent waves of infections. In particular, variants of concern (VOC) were identified to have both increased transmissibility and virulence ascribable to mutational changes occurring within the spike protein resulting to modifications in the protein structural orientation which in-turn may affect viral pathogenesis. However, this was never fully elucidated. Here, we generated spike models of endemic HCoVs (HCoV 229E, HCoV OC43, HCoV NL63, HCoV HKU1, SARS CoV, MERS CoV), original SARS2, and VOC (alpha, beta, gamma, delta). Model quality check, structural superimposition, and structural comparison based on RMSD values, TM scores, and contact mapping were all performed. We found that: 1) structural comparison between the original SARS2 and VOC whole spike protein model have minor structural differences (TM > 0.98); 2) the whole VOC spike models putatively have higher structural similarity (TM > 0.70) to spike models from endemic HCoVs coming from the same phylogenetic cluster; 3) original SARS2 S1-CTD and S1-NTD models are structurally comparable to VOC S1-CTD (TM = 1.0) and S1-NTD (TM > 0.96); and 4) endemic HCoV S1-CTD and S1-NTD models are structurally comparable to VOC S1-CTD (TM > 0.70) and S1-NTD (TM > 0.70) models belonging to the same phylogenetic cluster. Overall, we propose that structural similarities (possibly ascribable to similar conformational epitopes) may help determine immune cross-reactivity, whereas, structural differences (possibly associated with varying conformational epitopes) may lead to viral infection (either reinfection or breakthrough infection).

There is conflicting evidence of the roles vitamin D and iron have in isolation and combined in relation to muscle health. The purpose of this narrative review was to examine the current literature on the roles that vitamin D and iron have on skeletal muscle mass, strength, and function and how these nutrients are associated with skeletal muscle health in specific populations. Secondary purposes include exploring if low vitamin D and iron status are interrelated with skeletal muscle health and chronic inflammation and reviewing the influence of animal-source foods rich in these nutrients on health and performance. PubMed, Scopus, SPORT Discus, EMBAE, MEDLINE, and Google Scholar databases were searched to determine eligible studies. There was a positive effect of vitamin D on muscle mass, particularly in older adults. There was a positive effect of iron on aerobic and anaerobic performance. Studies reported mixed results for both vitamin D and iron on muscle strength and function. While vitamin D and iron deficiency commonly occur in combination, few studies examined effects on skeletal muscle health and inflammation. Isolated nutrients such as iron and vitamin D may have positive outcomes; however, nutrients within food sources may be most effective in improving skeletal muscle health.

The SARS-CoV-2 (SARS2) is the cause of the coronavirus disease 2019 (COVID-19) pandemic. One unique structural feature of the SARS2 spike protein is the presence of a furin-like cleavage site (FLC) which is associated with both viral pathogenesis and host tropism. Specifically, SARS2 spike protein binds to the host ACE-2 receptor which in-turn is cleaved by furin proteases at the FLC site, suggesting that SARS2 FLC structural variations may have an impact on viral infectivity. However, this has not yet been fully elucidated. This study designed and analyzed a COVID-19 genomic epidemiology network for December 2019 to July 2020, and subsequently generated and analyzed representative SARS2 spike protein models from significant node clusters within the network. To distinguish possible structural variations, a model quality assessment was performed before further protein model analyses and superimposition of the protein models, particularly in both the receptor-binding domain (RBD) and FLC. Mutant spike models were generated with the unique 681PRRA684 amino acid sequence found within the deleted FLC. We found 9 SARS2 FLC structural patterns that could potentially correspond to nine node clusters encompassing various countries found within the COVID-19 genomic epidemiology network. Similarly, we associated this with the rapid evolution of the SARS2 genome. Furthermore, we observed that either in the presence or absence of the unique 681PRRA684 amino acid sequence no structural changes occurred within the SARS2 RBD, which we believe would mean that the SARS2 FLC has no structural influence on SARS2 RBD and may explain why host tropism was maintained.

Coronaviruses (CoV) are enveloped positive-stranded RNA viruses and, historically, there are seven known human-infecting CoVs with varying degrees of virulence. CoV attachment to the host is the first step of viral pathogenesis and mainly relies on the spike glycoprotein located on the viral surface. Among the human-infecting CoVs, only the infection of SARS CoV 2 (SARS2) among humans resulted to a pandemic which would suggest that the protein structural conformation of SARS2 spike protein is distinct as compared to other human-infecting CoVs. Surprisingly, the possible differences and similarities in the protein structural conformation between the various human-infecting CoV spike proteins have not been fully elucidated. In this study, we utilized a computational approach to generate models and analyze the seven human-infecting CoV spike proteins, namely: HCoV 229E, HCoV OC43, HCoV NL63, HCoV HKU1, SARS CoV, MERS CoV, and SARS2. Model quality assessment of all CoV models generated, structural superimposition of the whole protein model and selected S1 domains (S1-CTD and S1-NTD), and structural comparison based on RMSD values, Tm scores, and contact mapping were all performed. We found that the structural orientation of S1-CTD is a potential structural feature associated to both the CoV phylogenetic cluster and lineage. Moreover, we observed that spike models in the same phylogenetic cluster or lineage could potentially have similar protein structure. Additionally, we established that there are potentially three distinct S1-CTD orientation (Pattern I, Pattern II, Pattern III) among the human-infecting CoVs. Furthermore, we postulate that human-infecting CoVs in the same phylogenetic cluster may have similar S1-CTD and S1-NTD structural orientation. Taken together, we propose that the SARS2 spike S1-CTD follows a Pattern III orientation which has a higher degree of similarity with SARS1 and some degree of similarity with both OC43 and HKU1 which coincidentally are in the same phylogenetic cluster and lineage, whereas, the SARS2 spike S1-NTD has some degree of similarity among human-infecting CoVs that are either in the same phylogenetic cluster or lineage.

Malnutrition and sarcopenia commonly overlap and contribute to adverse health outcomes. Previously, chronic supplementation with two oral nutritional supplements (ONS), control (CONS) and experimental ONS enriched with protein, vitamin D and β-hydroxy β-methylbutyrate (HMB) (EONS), improved muscle strength and quality in malnourished sarcopenic older adults, with EONS demonstrating early strength benefits at 12 weeks. To understand the underlying biological mechanisms contributing to the observed early strength benefits of EONS, we examined serum biomarker changes in response to 12-week supplementation. Serum samples (EONS (n = 90) and CONS (n = 103)) collected at baseline and 12 weeks were analyzed. Biomarkers (n = 243) were measured using multiplexed immunoassay, commercial immunoassays and ELISAs. Sixty markers were excluded with levels below assay detection limits. Sixteen biomarkers significantly changed in response to both interventions including nutritional and metabolic markers. Thirteen biomarkers significantly changed in response to EONS but not CONS. Increases in immunoglobulins, myoglobin, total protein, vitamin E and magnesium were observed with EONS. Inflammation-related ferritin and osteopontin decreased, while soluble receptors for cytokines increased, suggesting decreased inflammation. Sex hormone-binding globulin associated with sarcopenia also decreased with EONS. Biomarkers reflective of multiple biological systems were impacted by nutritional intervention in sarcopenic older adults. Incremental biomarker changes were observed in response to EONS containing HMB that possibly link to improvements in skeletal muscle health.

Purpose: The purposes of the present study were to (a) examine resting metabolism, substrate utilization, and endogenous versus exogenous carbohydrate (CHO) oxidation before and after 30-g rapidly-digesting carbohydrate (RDC) ingestion using indirect calorimetry and breath test analysis of stable isotope concentrations in pre-pubescent children and (b) report the 13C abundances in foods consumed for three days prior. Methods: Nineteen children (n = 10 boys, n = 9 girls) at Tanner stage I or II participated (mean age ± 95% CI = 9.84 ± 0.77 y) in this study. Food was administered to the children for three days preceding their scheduled breath tests. Breath tests and indirect calorimetry were performed after an 8-h fast before and 60 min following consumption of a 30-g simple RDC drink consisting of maltodextrin and sucrose. Open circuit spirometry and indirect calorimetry monitored resting metabolism and CHO oxidation. Separate breath samples were taken every 15 min. Samples of all foods and breath samples were analyzed for 13C and 12C abundances with a stable-isotope mass spectrometer. Results: 13C in expired breath samples were −23.81 ± 1.64‰ at baseline and increased every 15 min after consumption of the CHO drink (p

Controlling the oral microbial flora is putatively thought to prevent not only oral diseases, but also systemic diseases caused by oral diseases. This study establishes the antibacterial effect of the novel bioactive substance “S-PRG filler” on oral bacteria. We examined the state of oxidative stress caused by the six types of ions released in eluate from the S-PRG filler in oral bacterial cells. Moreover, we investigated the effects of these ions on the growth and pathogenicity of Gram-positive and Gram-negative bacteria. We found that the released ions affected SOD amount and hydrogen peroxide in bacterial cells insinuating oxidative stress occurrence. In bacterial culture, growth inhibition was observed depending on the ion concentration in the medium. Additionally, released ions suppressed Streptococcus mutans adhesion to hydroxyapatite, S. oralis neuraminidase activity, and Porphyromonas gingivalis hemagglutination and gingipain activity in a concentration-dependent manner. From these results, it was suggested that the ions released from the S-PRG filler may suppress the growth and pathogenicity of the oral bacterial flora. This bioactive material is potentially useful to prevent the onset of diseases inside and outside of the oral cavity, which in turn may have possible applications for oral care and QOL improvement.

Background The purpose of this study was to examine relationships among biomarkers of iron status, athletic performance, growth and development, and dietary intakes in pre-adolescent and adolescent male and female athletes. Methods Two-hundred and forty-nine male (n = 179) (mean ± standard deviation for age = 12.0 ± 2.1 years, height = 156.3 ± 13.9 cm, and weight = 49.1 ± 16.5 kg) and female (n = 70) (12.0 ± 2.2 years, 152.4 ± 12.3 cm, 45.3 ± 14.5 kg) athletes volunteered for capillary blood sample, anthropometric, athletic performance, and dietary intake assessments. Outcomes included maturity offset from peak height velocity, percent body fat, estimated muscle cross-sectional areas, vertical jump height (VJ), broad jump distance (BJ), pro-agility time (PA), L-cone time, 20-yard dash time (20YD), power push up (PPU) force, dietary intakes, and ferritin, soluble transferrin receptor (sTfR), and hemoglobin (Hb) concentrations. Results Athletic performance was consistently correlated with Hb in males (r = .237–.375, p 0.05). After partialing out age and height, VJ, PA, LC, and 20YD remained correlated with Hb in males (|r Hb,y.Age| = .208–.322, p = 0.001–0.041; |r Hb,y.Height| = .211–.321, p = 0.001–0.038). After partialing out iron intake, PA and LC remained correlated with sTfR in females (|r sTfR,y.ironintake| = .516–.569, p = 0.014–0.028). Conclusions Iron status biomarkers demonstrated sex-specific relationships with anaerobic exercise performance in youth athletes, which may be more dependent on maturity status and dietary intake than age. Moderate relationships between sTfR and athletic performance in adolescent female athletes emphasizes the importance of iron intake in this demographic.

Autophagy and redox biochemistry are two major sub disciplines of cell biology which are both coming to be appreciated for their paramount importance in the etiology of neurodegenerative diseases including Alzheimer's disease (AD). Thus far, however, there has been relatively little exploration of the interface between autophagy and redox biology. Autophagy normally recycles macro-molecular aggregates produced through oxidative-stress mediated pathways, and also may reduce the mitochondrial production of reactive oxygen species through recycling of old and damaged mitochondria. Conversely, dysfunction in autophagy initiation, progression or clearance is evidenced to increase aggregation-prone proteins in neural and extraneural tissues. Redox mechanisms of autophagy regulation have been documented at the level of cross-talk between the Nrf2/Keap1 oxidant and electrophilic defense pathway and p62/sequestosome-1 (SQSTM1)-associated autophagy, at least in extraneural tissue; but other mechanisms of redox autophagy regulation doubtless remain to be discovered and the relevance of such processes to maintenance of neural homeostasis remains to be determined. This review summarizes current knowledge regarding the relationship of redox signaling, autophagy control, and oxidative stress as these phenomena relate to neurodegenerative disease. AD is specifically addressed as an example of the theme and as a promising indication for new therapies that act through engagement of autophagy pathways. To exemplify one such novel therapeutic entity, data is presented that the antioxidant and neurotrophic agent lanthionine ketimine-ethyl ester (LKE) affects autophagy pathway proteins including beclin-1 in the 3xTg-AD model of Alzheimer's disease where the compound has been shown to reduce pathological features and cognitive dysfunction.

Autophagy is a fundamental cellular recycling process vulnerable to compromise in neurodegeneration. We now report that a cell-penetrating neurotrophic and neuroprotective derivative of the central nervous system (CNS) metabolite, lanthionine ketimine (LK), stimulates autophagy in RG2 glioma and SH-SY5Y neuroblastoma cells at concentrations within or below pharmacological levels reported in previous mouse studies. Autophagy stimulation was evidenced by increased lipidation of microtubule-associated protein 1 light chain 3 (LC3) both in the absence and presence of bafilomycin-A1 which discriminates between effects on autophagic flux versus blockage of autophagy clearance. LKE treatment caused changes in protein level or phosphorylation state of multiple autophagy pathway proteins including mTOR; p70S6 kinase; unc-51-like-kinase-1 (ULK1); beclin-1 and LC3 in a manner essentially identical to effects observed after rapamycin treatment. The LKE site of action was near mTOR because neither LKE nor the mTOR inhibitor rapamycin affected tuberous sclerosis complex (TSC) phosphorylation status upstream from mTOR. Confocal immunofluorescence imaging revealed that LKE specifically decreased mTOR (but not TSC2) colocalization with LAMP2+ lysosomes in RG2 cells, a necessary event for mTORC1-mediated autophagy suppression, whereas rapamycin had no effect. Suppression of the LK-binding adaptor protein CRMP2 (collapsin response mediator protein-2) by means of shRNA resulted in diminished autophagy flux, suggesting that the LKE action on mTOR localization may occur through a novel mechanism involving CRMP2-mediated intracellular trafficking. These findings clarify the mechanism-of-action for LKE in preclinical models of CNS disease, while suggesting possible roles for natural lanthionine metabolites in regulating CNS autophagy.

Fusobacterium nucleatum (Fn) is generally an opportunistic oral pathogen that adheres to mammalian mucosal sites, triggering a host inflammatory response. In general, Fn is normally found within the human oral cavity; however, it was previously reported that Fn is a risk factor for certain respiratory diseases. Surprisingly, this was never fully elucidated. Here, we investigated the virulence potential of heat-killed Fn on primary human tracheal, bronchial, and alveolar epithelial cells. In this study, we measured the secretion of inflammatory- (IL-8 and IL-6), stress- (total heme and hydrogen peroxide), and cell death-related (caspase-1 and caspase-3) signals. We established that the inflammatory response mechanism varies in each epithelial cell type: (1) along tracheal cells, possible Fn adherence would trigger increased heme secretion and regulated inflammatory response; (2) along bronchial cells, potential Fn adherence would simultaneously initiate an increase in secreted H2O2 and inflammatory response (ascribable to decreased secreted heme amounts); and (3) along alveolar cells, putative Fn adherence would instigate the increased secretion of inflammatory responses attributable to a decrease in secreted heme levels. Moreover, regardless of the epithelial cell-specific inflammatory mechanism, we believe these are putative, not harmful. Taken together, we propose that any potential Fn-driven inflammation along the respiratory tract would be initiated by differing epithelial cell-specific inflammatory mechanisms that are collectively dependent on secreted heme.

Butyric acid (BA) is produced by periodontopathic bacterial pathogens and contributes to periodontal disease (PD) induction. Moreover, PD has been associated with detrimental effects which subsequently may lead to systemic disease (SD) development affecting certain organs. Surprisingly, the potential systemic manifestations and organ-localized effects of BA have never been elucidated. Here, we simulated BA-based oral infection among young (20-week-old) rats and isolated blood cytosol to determine BA effects on stress network-related signals [total heme, hydrogen peroxide (H2O2), catalase (CAT), glutathione reductase (GR), free fatty acid (FFA), NADP/NADPH], inflammation-associated signals [caspases (CASP12 and CASP1), IL-1β, TNF-α, metallomatrix proteinase-9 (MMP-9), and toll-like receptor-2 (TLR2)], and neurological blood biomarkers [presenilin (PS1 and PS2) and amyloid precursor protein (APP)]. Similarly, we extracted the brain from both control and BA-treated rats, isolated the major regions (hippocampus, pineal gland, hypothalamus, cerebrum, and cerebellum), and, subsequently, measured stress network-related signals [oxidative stress: total heme, NADPH, H2O2, GR, and FFA; ER stress: GADD153, calcium, CASP1, and CASP3] and a brain neurodegenerative biomarker (Tau). In the blood, we found that BA was no longer detectable. Nevertheless, oxidative stress and inflammation were induced. Interestingly, amounts of representative inflammatory signals (CASP12, CASP1, IL-1β, and TNF-α) decreased while MMP-9 levels increased which we believe would suggest that inflammation was MMP-9-modulated and would serve as an alternative inflammatory mechanism. Similarly, TLR2 activity was increased which would insinuate that neurological blood biomarkers (APP, PS1, and PS2) were likewise affected. In the brain, BA was not detected, however, we found that both oxidative and ER stresses were likewise altered in all brain regions. Interestingly, tau protein amounts were significantly affected in the cerebellar and hippocampal regions which coincidentally are the major brain regions affected in several neurological disorders. Taken together, we propose that gingival BA can potentially cause systemic inflammation ascribable to prolonged systemic manifestations in the blood and localized detrimental effects within the brain organ.

Over the last 20 years, Hawaii’s agriculture has shifted from a focus on sugar cane (Saccharum officinarum) and pineapples (Ananas comosus) produced on large farms to a diverse array of products produced on a multitude of smaller farms. This dramatic shift in production, in addition to the introduction of many new avian species, has resulted in a concomitant change in the problems faced by agriculture. We surveyed farmers to determine the extent of bird damage to crops, the species responsible, the crops most vulnerable, and control methods employed. Bird problems varied by island, but cardinals (Cardinalis cardinalis, Paroaria coronata, and P. capitata) and pheasants (Phasianus colchicus and Lophura leucomelanos) were significant problems on all islands. Seed corn (Zea mays), fruit, vegetables, rice (Oryza sativa), and orchids (Orchidaceae) all sustained notable damage to their crops by birds, and growers expressed much interest in gaining information on control measures. Most farmers incurred little damage, while a few reported losing 80 to 100% of their crops at certain times of the year. We recommend a multidimensional approach to control invasive bird species, including habitat alterations, scare tactics, cessation of game bird releases, prevention of the spread of known pests among islands, and the development of chemical repellents for use when other methods are not sufficient.

Abstract Introduction Disruptive behavior problems are the most common referral reason to behavioral health professionals among preschool-age children. Parent management training (PMT) is the primary intervention for the treatment of disruptive behaviors, but current programs have high attrition rates in part due to their length. The Brief Behavioral Intervention (BBI) is a manualized parent management training PMT designed specifically to have fewer sessions in order to limit attrition associated with attending a long series of sessions and for easy implementation in hospital clinics and outpatient settings. Methods BBI consists of five core sessions, each focused on a specific behavioral management skill. These sessions occur on a weekly basis and last from 45 minutes to 1 hour per session, with one booster session after the first 2 weeks if needed. Thus, the intervention lasts from 5–7 weeks. The BBI manual is intended to be used by experienced professionals as a self-teaching guide or by faculty for teaching graduate and medical students interventions for children with disruptive behaviors. Results To date, we have trained seven faculty members, 14 postdoctoral fellows, 44 predoctoral interns, and 19 predoctoral practicum students using this manual. Many of those students use the BBI manual in their daily work. Over the years, we have received positive quantitative and qualitative feedback from the learners. Discussion The creation of this manual, coupled with supervised implementation, has resulted in a new generation of therapists trained in evidence-based strategies within a model brief enough to maintain patient participation and easy to export to myriad settings.

Cytokines such as TNFα can polarize microglia/macrophages into different neuroinflammatory types. Skewing of the phenotype towards a cytotoxic state is thought to impair phagocytosis and has been described in Alzheimer's Disease (AD). Neuroinflammation can be perpetuated by a cycle of increasing cytokine production and maintenance of a polarized activation state that contributes to AD progression. In this study, 3xTgAD mice, age 6 months, were treated orally with 3 doses of the TNFα modulating compound isoindolin-1,3 dithione (IDT) for 10 months. We demonstrate that IDT is a TNFα modulating compound both in vitro and in vivo. Following long-term IDT administration, mice were assessed for learning & memory and tissue and serum were collected for analysis. Results demonstrate that IDT is safe for long-term treatment and significantly improves learning and memory in the 3xTgAD mouse model. IDT significantly reduced paired helical filament tau and fibrillar amyloid accumulation. Flow cytometry of brain cell populations revealed that IDT increased the infiltrating neutrophil population while reducing TNFα expression in this population. IDT is a safe and effective TNFα and innate immune system modulator. Thus small molecule, orally bioavailable modulators are promising therapeutics for Alzheimer's disease.

Influenza A hemagglutinin (HA) is a homotrimeric glycoprotein composed of a fibrous globular stem supporting a globular head containing three sialic acid binding sites responsible for infection. The H7N9 strain has consistently infected an avian host, however, the novel 2013 strain is now capable of infecting a human host which would imply that the HA in both strains structurally differ. A better understanding of the structural differences between the avian and human H7N9 strains may shed light into viral evolution and transmissibility. In this study, we elucidated the structural differences between the avian and human H7N9 strains. Throughout the study, we generated HA homology models, verified the quality of each model, superimposed HA homology models to determine structural differences, and, likewise, elucidated the probable cause for these structural differences. We detected two different types of structural differences between the novel H7N9 human and representative avian strains, wherein, one type (Pattern-1) showed three non-overlapping regions while the other type (Pattern-2) showed only one non-overlapping region. In addition, we found that superimposed HA homology models exhibiting Pattern-1 contain three non-overlapping regions designated as: Region-1 (S1571-A1601); Region-3 (R2621-S2651); and Region-4 (S2701-D2811), whereas, superimposed HA homology models showing Pattern-2 only contain one non-overlapping region designated as Region-2 (S1371-S1451). We attributed the two patterns we observed to either the presence of salt bridges involving the E1141 residue or absence of the R1411:D771 salt bridge. Interestingly, comparison between the human H7N7 and H7N9 HA homology models showed high structural similarity. We propose that the putative absence of the R1411:D771 salt bridge coupled with the putative presence of the E1141:R2621 and E1141:K2641 salt bridges found in the 2013 H7N9 HA homology model is associated to human-type receptor binding. This highlights the possible significance of HA salt bridge formation modifications in viral infectivity, immune escape, transmissibility and evolution.

RASopathies are a group of genetic disorders that are caused by genes that affect the canonical Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Despite tremendous progress in understanding the molecular consequences of these genetic anomalies, little movement has been made in translating these findings to the clinic. This year, the seventh International RASopathies Symposium focused on expanding the research knowledge that we have gained over the years to enhance new discoveries in the field, ones that we hope can lead to effective therapeutic treatments. Indeed, for the first time, research efforts are finally being translated to the clinic, with compassionate use of Ras/MAPK pathway inhibitors for the treatment of RASopathies. This biannual meeting, organized by the RASopathies Network, brought together basic scientists, clinicians, clinician scientists, patients, advocates, and their families, as well as representatives from pharmaceutical companies and the National Institutes of Health. A history of RASopathy gene discovery, identification of new disease genes, and the latest research, both at the bench and in the clinic, were discussed.

T cells are critical effectors of cancer immunotherapies, but little is known about their gene expression programs in diffuse gliomas. Here, we leverage single-cell RNA sequencing (RNA-seq) to chart the gene expression and clonal landscape of tumor-infiltrating T cells across 31 patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma and IDH mutant glioma. We identify potential effectors of anti-tumor immunity in subsets of T cells that co-express cytotoxic programs and several natural killer (NK) cell genes. Analysis of clonally expanded tumor-infiltrating T cells further identifies the NK gene KLRB1 (encoding CD161) as a candidate inhibitory receptor. Accordingly, genetic inactivation of KLRB1 or antibody-mediated CD161 blockade enhances T cell-mediated killing of glioma cells in vitro and their anti-tumor function in vivo. KLRB1 and its associated transcriptional program are also expressed by substantial T cell populations in other human cancers. Our work provides an atlas of T cells in gliomas and highlights CD161 and other NK cell receptors as immunotherapy targets.

Using prismatic inquiry, a team of researchers documented a variety of personal experiences that spanned elementary through higher education, with the goal of determining what helped and what was needed to improve the adaptability of our educational system during the COVID-19 emergency. Three analytical teams identified that students remained at the heart of the conversation, supported by leadership, teachers, parents, and the students themselves. Furthermore, all four groups needed, in differing ways: (a) connection, (b) voice, (c) social-emotional skills, and (d) academic knowledge.

Purpose: The purpose of this study was to determine magnitudes of differences for anthropometric and athletic performance scores between high school and elite college-level American football players. Method: Participants included high school-age (n = 3,666) athletes who participated in American football combines, as well as elite college-level (n = 5,537) athletes who participated in the National Football League (NFL) scouting combine. Combine data included position; height; weight; 10-, 20-, and 40-yard dash; pro-agility (PA); L-cone drill (LC); vertical jump (VJ); and broad jump (BJ). Athletes were separated into their respective position group, defensive back (DB), wide receiver (WR), linebacker (LB), quarterback (QB), running back (RB), tight end (TE), defensive line (DL), and offensive line (OL) for analysis of performance differences. Percent differences for each dependent variable were calculated to quantify magnitudes of differences. Results: NFL combine participants scored 3% to 25% better on all measurements, with the largest differences between weight and VJ (14%-25%). Conclusion: The largest measurement-specific differences between high school-age and elite college-level American football players were body size and power. Although it may seem intuitive that elite college-level players would perform better, these data provide a unique perspective to high school players, parents, and coaches, giving new information to use when designing measurement-specific athletic development programs. Thus, strength and conditioning professionals may benefit from emphasizing increases in muscle mass and power output in strength and conditioning programs.

Synovial sarcoma (SyS) is an aggressive neoplasm driven by the SS18-SSX fusion, and is characterized by low T cell infiltration. Here, we studied the cancer-immune interplay in SyS using an integrative approach that combines single-cell RNA sequencing (scRNA-seq), spatial profiling and genetic and pharmacological perturbations. scRNA-seq of 16,872 cells from 12 human SyS tumors uncovered a malignant subpopulation that marks immune-deprived niches in situ and is predictive of poor clinical outcomes in two independent cohorts. Functional analyses revealed that this malignant cell state is controlled by the SS18-SSX fusion, is repressed by cytokines secreted by macrophages and T cells, and can be synergistically targeted with a combination of HDAC and CDK4/CDK6 inhibitors. This drug combination enhanced malignant-cell immunogenicity in SyS models, leading to induced T cell reactivity and T cell-mediated killing. Our study provides a blueprint for investigating heterogeneity in fusion-driven malignancies and demonstrates an interplay between immune evasion and oncogenic processes that can be co-targeted in SyS and potentially in other malignancies. Single-cell transcriptional profiling of primary human synovial sarcoma tumors suggests that combinatorial treatment with HDAC and CDK4/CDK6 inhibitors could enhance tumor immunogenicity., Author(s): Livnat Jerby-Arnon [sup.1] [sup.2] [sup.3] [sup.4] , Cyril Neftel [sup.3] [sup.4] [sup.5] [sup.6] , Marni E. Shore [sup.3] [sup.4] [sup.5] , Hannah R. Weisman [sup.3] [sup.4] [sup.5] , Nathan [...]

Background: Testing and evaluating athletes is necessary and should include performance, body composition, and nutrition. The purpose of this study was to report assessments of dietary intake, V ˙ O2max, and body composition in D1 collegiate athletes and examine relationships between these assessments. Methods: Dietary intake was assessed with 3-day recalls and compared to recommendations, and body composition was assessed via bioelectrical impedance analysis (BIA) (n = 48). V ˙ O2max was evaluated using a graded exercise test (GXT) with a verification bout (n = 35). Reliability between "true" V ˙ O2max and verification was determined. Correlations and regressions were performed. Results: Energy, carbohydrate, and micronutrient intake was lower than recommendations. Mean V ˙ O2max was 47.3 and 47.4 mL·kg−1·min−1 for GXT and verification, respectively. While correlations were apparent among dietary intake, V ˙ O2max, and body composition, percent fat-free mass (%FFM) predicted 36% of V ˙ O2max. Conclusions: Collegiate athletes are not meeting energy and carbohydrate recommendations and exceed fat recommendations. Vitamin D and magnesium were low in all sports, and iron and calcium were low in females. V ˙ O2max ranged from 35.6 to 63.0 mL·kg−1·min−1, with females below average and males meeting typical values for their designated sport. Assessing D1 athletes can provide guidance for sports dietitians, coaches, and strength and conditioning specialists to track and monitor nutrition in athletes. [ABSTRACT FROM AUTHOR]