Placing the keystone: the LIMBIC Military and Tactical Athlete Research Study.

OBJECTIVE: The LIMBIC Military and Tactical Athletic Research Study (MATARS) framework was established to confirm and extend understanding of concussion with initial studies driven by clinical data collected between 2015 and 2020 in a collegiate sports setting. The LIMBIC MATARS framework will be leveraged to apply gold-standard and innovative research designs to advance the science of concussion. This manuscript provides the background, methodology, and initial demographic data associated with the LIMBIC MATARS. METHODS: Consensus-based common data elements were used to conduct a retrospective chart review, specific to collegiate athletes diagnosed with concussions between 2015 and 2020 at 11 universities. RESULTS: A final sample of 1,311 (47.8% female) concussions were diagnosed during the five-year study period from athletes participating in a variety of National Collegiate Athlete Association (NCAA) sports. The LIMBIC MATARS demographic data, align with the NCAA and other pioneering multi-site concussion-related studies in terms of biological sex, race and ethnicity, and sport participation. CONCLUSION: This pragmatic, methodological approach was used to address several a priori hypotheses related to concussion, align with other multi-site studies of concussion, and establish a consortium for future investigations.

Lost in translation: the association of international status and native language on concussion in collegiate athletes in the United States.

OBJECTIVE: The purpose of this study was to characterize the associations of international student status and native language on time (in days) with the date of injury to (i) diagnosis, (ii) symptom resolution, and (iii) return to sport. METHODS: Utilizing data from a cross-sectional cohort of 1,044 concussion cases from LIMBIC MATARS member institutions (n = 11) in the US, we conducted two, matched case-control designs. Cases were divided into two groups: (i) international (n = 32) or domestic students (n = 32) and (ii) English as an Additional Language (EAL) speakers (n = 18) or Native English language speakers (n = 18). Both groups were individually matched to their respective controls based on gender, age, sport, and preexisting health conditions. RESULTS: There were no significant differences in days from injury to diagnosis (p = 0.94), symptom resolution (p = 0.64), or return to sport (p = 0.15) between international and domestic athletes. EAL speakers experienced symptom resolution approximately 7.5 days sooner (Md = 4.50; IQR = 4.00, 8.00) than Native English language speakers (Md = 12.00; IQR = 7.00, 21.00, p = 0.01). CONCLUSIONS: Our findings suggest that native language is associated with symptom resolution in collegiate athletes. Healthcare professionals should consider barriers related to native language that may impact symptom reporting and the overall injury experience of diverse collegiate athletes.

Racial identity and concussion diagnosis and recovery trajectories in collegiate athletes: a LIMBIC MATARS investigation.

OBJECTIVE: To determine if there were concussion diagnosis and recovery disparities between collegiate athletes with Black and White racial identities. DESIGN: Retrospective cohort study. METHODS: Concussion information was extracted from NCAA athlete medical files at LIMBIC MATARS member institutions from the 2015-16' to 2019-20' academic years. A total of 410 concussions from 9 institutions were included that provided all independent (i.e. racial identity of Black or White) and dependent variable information (i.e. dates of injury, diagnosis, symptom resolution, and return to sport) that were analyzed using Mann-Whitney U tests. The sample consisted of 114 (27.8%) concussions sustained by Black athletes and 296 (72.1%) sustained by White athletes. RESULTS: The overall sample had a median of 0 days between injury occurrence to diagnosis, 7 days to symptom resolution, and 12 days to return to sport. No significant timing differences were observed for concussion diagnosis (p = .14), symptom resolution (p = .39), or return to sport (p = 0.58) between collegiate athletes with Black versus White racial identities. CONCLUSIONS: These findings may reflect equitable access to onsite sports medicine healthcare resources that facilitate concussion management in the collegiate sport setting. Future work should explore these associations with a larger and more diverse sample of collegiate athletes.

N-acetylcysteine decreases binge eating in a rodent model.

Binge-eating behavior involves rapid consumption of highly palatable foods leading to increased weight gain. Feeding in binge disorders resembles other compulsive behaviors, many of which are responsive to N-acetylcysteine (NAC), which is a cysteine prodrug often used to promote non-vesicular glutamate release by a cystine-glutamate antiporter. To examine the potential for NAC to alter a form of compulsive eating, we examined the impact of NAC on binge eating in a rodent model. Specifically, we monitored consumption of standard chow and a high-fat, high carbohydrate western diet (WD) in a rodent limited-access binge paradigm. Before each session, rats received either a systemic or intraventricular injection of NAC. Both systemic and central administration of NAC resulted in significant reductions of binge eating the WD without decreasing standard chow consumption. The reduction in WD was not attributable to general malaise as NAC did not produce condition taste aversion. These results are consistent with the clinical evidence of NAC to reduce or reverse compulsive behaviors, such as, drug addiction, skin picking and hair pulling.

Barriers to the long-term recovery of individuals with disabilities following a disaster.

This study examines how pre-existing disabling conditions influenced the recovery process of survivors of Hurricane Katrina. It focuses specifically on the barriers that hindered the recovery process in these individuals. Focus groups were convened in four Gulf Coast states with 31 individuals with disabilities who lived in or around New Orleans, Louisiana, prior to Hurricane Katrina in August 2005. Qualitative data were analysed using grounded theory methodology. Five themes emerged as the most significant barriers to recovery: housing; transportation; employment; physical and mental health; and accessing recovery services. While these barriers to recovery were probably common to most survivors of the disaster, the research results suggest that disability status enhanced the challenges that participants experienced in negotiating the recovery process and in acquiring resources that accommodated their disabilities. The findings indicate that, when disaster recovery services and resources did not accommodate the needs of individuals with disabilities, recovery was hindered. Recovery efforts should include building accessible infrastructure and services that will allow for participation by all.

Depression among parents of children with disabilities.

We examined the rate of depression among 110 parents of children with disabilities and tested a model to determine the unique factors associated with parental depression. Consenting parents completed measures of depression, family satisfaction, physical health, problem-solving abilities, stress appraisals, and child functional impairment. Participants were categorized as depressed or nondepressed based on their responses to the Patient Health Questionnaire (PHQ9; Kroenke, Spitzer, & Williams, 2001). Nineteen percent of the parents met screening criteria for depression. Regression analyses revealed that threat appraisals, poorer physical health, and lower family satisfaction were uniquely associated with depression status with 83.3% accuracy. These findings highlight the importance of family satisfaction, problem solving ability, physical health, and the influence of appraisal processes on depression among parents of children with disabilities.

Evaluating a dynamic process model of wellbeing for parents of children with disabilities: a multi-method analysis.

PURPOSE: The purpose of this study was to evaluate possible determinants of parent wellbeing using a contextual model of parent adjustment. METHOD: One hundred forty parents of children with various disabilities (i.e., autism, intellectual disabilities, and other health impairments) participated in this investigation. Parents completed a survey consisting of basic demographic characteristics of the parent, child-disability characteristics, parent problem solving ability, access to information and resources, environmental/social supports, appraisals of threat and growth, and measures of life satisfaction and physical/mental health. Structural equation modeling was conducted to test a hypothesized contextual model of parent wellbeing. RESULTS: Results indicated strong fit to the a priori model. After controlling for the contribution of parent demographic variables, the largest contributors to the prediction of parent wellbeing were parent problem solving ability, access to resources, environmental/social supports, and parent appraisals of threat. Child functional impairment was not significantly associated with parent wellbeing. CONCLUSIONS: Access to resources and environmental/social supports have a greater direct effect on parent wellbeing than parent and child demographic variables and disability severity. Threat appraisals have direct and mediating effects on parent wellbeing. Implications related to the importance of resources and environmental/social supports, appraisals of threat and growth, and problem solving abilities on the wellbeing of parents of children with disabilities are discussed.

Giving parents a voice: A qualitative study of the challenges experienced by parents of children with disabilities.

BACKGROUND: This study sought to examine the specific sources of challenges as identified by parents of children with disabilities. METHOD: Focus groups were conducted with 40 parent caregivers. Data gathered were coded into themes which were then analyzed through an intentional process of data reduction that resulted in the cross site validation of four superordinate themes. RESULTS: Four themes emerged as the most prominent barriers to positive parent wellbeing: (a) access to information and services, (b) financial barriers, (c) school and community inclusion, and (d) family support. These four themes are indicative of problems associated with a lack of match between caregiver needs and services, resources, or support available in the community to meet those needs. CONCLUSION: Caring for a child with a disability can be challenging, but many of these challenges are likely due to a lack of necessary environmental supports. Future research should expand on these findings and policy makers, scientists and providers should give particular attention to the environmental support needs of parents in order to create policies and interventions that are more family-centered.

Family satisfaction predicts life satisfaction trajectories over the first 5 years after traumatic brain injury.

OBJECTIVES: Examined the influence of functional impairment, stable marital status, and family satisfaction on life satisfaction trajectories for 609 individuals (435 men, 174 women) over the first 5 years after traumatic brain injury (TBI). MEASURES: Participants completed the Family Satisfaction Scale (FSS), Functional Independence Measure (FIM), and the Life Satisfaction Index (LSI) at years 1, 2, 4, and 5 after sustaining a TBI. RESULTS: Trajectory modeling revealed that higher family satisfaction was associated with increases in life satisfaction for individuals with less functional impairment. Stable marital status was not significantly associated with life satisfaction trajectories. IMPLICATIONS: Family satisfaction appears to have pronounced beneficial effects on life satisfaction for persons with less functional impairment after TBI regardless of marital status. In contrast, a stable marriage appears to have no apparent benefits to self-reported life satisfaction over the first 5 years post-TBI. Theoretical and clinical implications of these results are discussed.

Expression of hypoxia-inducible factor 1 alpha in thyroid carcinomas.

Hypoxia-inducible factor 1 alpha (HIF-1 alpha) is upregulated by hypoxia and oncogenic signalling in many solid tumours. Its regulation and function in thyroid carcinomas are unknown. We evaluated the regulation of HIF-1 alpha and target gene expression in primary thyroid carcinomas and thyroid carcinoma cell lines (BcPAP, WRO, FTC-133 and 8505c). HIF-1 alpha was not detectable in normal tissue but was expressed in thyroid carcinomas. Dedifferentiated anaplastic tumours (ATCs) exhibited high levels of nuclear HIF-1 alpha staining. The HIF-1 target glucose transporter 1 was expressed to a similar level in all tumour types, whereas carbonic anhydrase-9 was significantly elevated in ATCs. In vitro studies revealed a functionally active HIF-1 alpha pathway in thyroid cells with transcriptional activation observed after graded hypoxia (1% O(2), anoxia) or treatment with a hypoxia mimetic cobalt chloride. High basal and hypoxia-induced expression of HIF-1 alpha in FTC-133 cells that harbour a phosphatase and tensin homologue (PTEN) mutation was reduced by introduction of wild-type PTEN. Similarly, pharmacological inhibition of the phosphoinositide 3-kinase (PI3K) pathway using LY294002 inhibited HIF-1 alpha and HIF-1 alpha targets in all cell lines, including those with B-RAF mutations (BcPAP and 8505c). In contrast, the effects of inhibition of the RAF/MEK/extracellular signal-regulated kinase pathway were restricted by environmental condition and B-RAF mutation status. HIF-1 is functionally expressed in thyroid carcinomas and is regulated not only by hypoxia but also via growth factor signalling pathways and, in particular, the PI3K pathway. Given the strong association of HIF-1 alpha with an aggressive disease phenotype and therapeutic resistance, this pathway may be an attractive target for improved therapy in thyroid carcinomas.

Trajectories of life satisfaction in the first 5 years following traumatic brain injury.

OBJECTIVES: The trajectories of life satisfaction for 609 individuals who sustained a traumatic brain injury (TBI) were studied. Hierarchical linear modeling analysis examined individual level growth trends over the first 5 years following TBI using gender, functional independence, age, and time to estimate life satisfaction trajectories. MEASURES: Participants completed the Functional Independence Measure and the Life Satisfaction Inventory at years 1, 2, 4, and 5 after sustaining TBI. RESULTS: Participants who reported higher functional independence at year 1 also had higher life satisfaction at year 1. Participants with lower functional independence across the 5-year period had life satisfaction trajectories that decreased at significantly greater rates than the individuals with more functional independence. The life satisfaction trajectory declined for the sample, but participants reporting lower cognitive and motor functional independence had significantly greater declines in life satisfaction trajectories. Age and gender were not significant factors in predicting life satisfaction trajectories following TBI. IMPLICATIONS: Individuals with greater cognitive and motor impairments following TBI are likely to experience significant declines in life satisfaction within 5 years of living with TBI.

Lithium stimulates proliferation in cultured thyrocytes by activating Wnt/beta-catenin signalling.

BACKGROUND: Lithium, clinically used in the treatment of bipolar disorders, is well known to induce thyroid growth. However, the mechanism involved is only incompletely characterized. Although it is conventionally believed that thyroid proliferation depends on the thyroid-stimulating hormone (TSH)/cAMP/cAMP response element binding protein (CREB) pathway, recent data indicate that Wnt/beta-catenin signalling may be of critical importance. In other cell types lithium activates canonical Wnt signalling by GSK-3beta inhibition, which in turn stabilizes cytosolic free beta-catenin. Here we investigated the potential modulation of Wnt/beta-catenin signalling under lithium treatment in primary and neoplastic human thyrocytes. METHODS: Primary (S18) and neoplastic (NPA, FTC133) thyrocytes treated with and without LiCl were analysed using Western blotting, immunoprecipitation, reporter-gene assay, MTT proliferation assay and transfection studies. RESULTS: LiCl dose-dependently inhibited GSK-3beta, stabilized free beta-catenin and inhibited beta-catenin degradation. Furthermore, LiCl altered the assembly of adherens junction by upregulating the E-cad-herin repressor, Snail, and downregulated E-cadherin expression. At a dose of 5 mM, LiCl significantly increased the proliferative potency of thyrocytes, which appeared to be mediated by beta-catenin, since nuclear beta-catenin stimulated T-cell factor/lymphoid enhancer factor (TCF/LEF)-mediated transcription and upregulated downstream targets like cyclin D1. To characterize the specificity of Wnt/beta-catenin-driven thyrocyte proliferation, we transfected primary thyrocytes and FTC133 cells with dominant negative TCF4 to block Wnt-dependent pathways or with dominant negative CREB to inhibit the TSH/cAMP cascade. In cells transfected with dominant negative CREB lithium-stimulated proliferation was unchanged whereas blocking Wnt/beta-catenin by dominant negative TCF4 reduced proliferation by approx. 50%. CONCLUSION: Our data indicate that Wnt/beta-catenin signalling is of major importance in the control of lithium-dependent thyrocyte proliferation.

[Geographic distribution of multiple sclerosis and comparison with geophysical values]. / Geographische Verteilung der Multiplen Sklerose und Vergleich mit geophysikalischen Grössen.

This work is based on former investigations describing the similarity between the distribution of MS-frequency and solar particle rays. The analysis of the prevalence values shows clearly that the global MS-frequency is closer related to the geomagnetic than to the geographic latitude. This relation is best described by a Gaussian curve: in temperate latitudes the MS-frequency increases rapidly in pole direction and decreases again in pole-proximity. The MS-distribution shows a spatial relation to the distribution of solar particle rays and geomagnetic activity and to the external radiation belt of the earth. Further considerations are being made including the 11-year-sun-cycle.

A novel potent non-benzodiazepine anxioselective agent with reduced dependence liability: ICI 198, 256.

ICI 198,256, a member of the cinnoline series, was shown to be a potent anxiolytic agent in several species of animals. In addition, ICI 198,256 exhibited potent activity as an antagonist of both metrazole and bicuculline-induced convulsions. The salient features of ICI 198,256 are that it possesses minimal sedative liability, lower ethanol interaction and possibly lower dependence liability than benzodiazepines (e.g., diazepam). Neurochemically, this structurally novel anxiolytic compound is potent and selective for the Type 1 (cerebellar) BZ receptors in vivo as well as ex vivo, and in addition shows an agonist BZ-like profile in a variety of systems. Thus, ICI 198,256 may offer several significant advantages in the treatment of anxiety in humans than existing benzodiazepines.

Synthesis and structure-activity relationships of a series of anxioselective pyrazolopyridine ester and amide anxiolytic agents.

A series of 1-substituted 4-amino-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid esters and amides were synthesized and screened for anxiolytic activity in the shock-induced suppression of drinking (SSD) test. The compounds were also tested for their ability to displace [3H]flunitrazepam (FLU) from brain benzodiazepine (BZ) binding sites. Many compounds were active in these screens and, additionally, demonstrated a selectivity for the type 1 BZ (BZ1) receptor over the type 2 BZ (BZ2) receptor as indicated by Hill coefficients significantly less than unity and by analysis of [3H]FLU binding results from different brain regions. Based on the results of structure-activity studies of these compounds, a hypothesis was proposed to explain the structural features necessary for optimal interaction with brain BZ receptors. A detailed pharmacological evaluation of one of the most potent behaviorally active compounds (27) demonstrated it to be BZ1 selective; also, in comparison to diazepam, 27 showed minimal sedative and alcohol interactive properties at therapeutically effective doses.

Serum lipids and lipoproteins as predictors of atherosclerosis. An autopsy study.

A prospective study of autopsy-determined measures of atherosclerosis in aortas and coronary and cerebral arteries was completed for a group of 83 men who were free of clinical cardiovascular disease and cancer when they entered the Cooperative Lipoprotein Phenotyping Study in 1970. Total cholesterol minus high density lipoprotein cholesterol (HDL-C) was significantly associated with measures of atherosclerosis in all three groups of vessels. The patterns of associations for total, low density lipoprotein, and very low density lipoprotein cholesterol were similar but generally weaker and not significant for atherosclerosis in the cerebral arteries. Inverse associations of HDL-C with atherosclerosis in the circle of Willis and aorta were significant, but those for the coronary arteries were not. These associations were independent of other major risk factors for atherosclerosis in multivariate analyses. Similarities between these findings and those for clinical cardiovascular disease in the same cohort indicate that the opposing patterns of increased risk of clinical cardiovascular disease associated with total cholesterol and the decreased risk associated with HDL-C also exists at the level of atherosclerosis in a variety of arteries.

[Caries morbidity in infants and preschool children with reference to social factors of influence]. / Kariesmorbidität von Klein- und Vorschulkindern unter Berücksichtigung sozialer Einflussgrössen.

The caries frequency of 653 children between 2-4 years of age was followed up over 2 years. Only very few of two year old children showed a relative high incidence of caries. Among the 4 year old children the incidence of caries was particularly high. Caries is more prevalent among children who stay at home than among those attending créches. The difference is due to the absence or irregular use of fluoride tablets, to inadequate cleaning of teeth and a high consumption of sweets in the families. Pre-school children without siblings, and those whose parents are working in shifts, should more often undergo stomatological supervision because of their greater risk suspectibility to caries.

Biparental defensive endowment of eggs with acquired plant alkaloid in the moth Utetheisa ornatrix.

The eggs of Utetheisa ornatrix contain pyrrolizidine alkaloids. These compounds are contributed by both parents, who sequester them as larvae from their food plants. Females receive alkaloid from the males at mating, apparently by seminal infusion, and transmit this alkaloid together with alkaloid of their own to the eggs. Field and laboratory tests showed that the alkaloids protect eggs from predators. The alkaloidal contribution of the male, although smaller than that of the female, itself provides significant egg protection. A previously identified pheromone, derived by the male from the alkaloid and emitted during precopulatory behavior, may announce the male alkaloidal worth to the female.

A prospective study of cerebral artery atherosclerosis.

Atherosclerosis in the circle of Willis and its major branches was studied prospectively in 198 men in the Honolulu Heart Program who were free of cardiovascular disease at the entry examination. The level of atherosclerosis was greater in the large arteries of the circle of Willis than in the small arteries, and autopsy-verified cerebral infarction was strongly associated with increasing severity of atherosclerosis in both. Analyses of the association of atherosclerosis scores with biologic and lifestyle characteristics measured at entry into the study indicated that atherosclerosis in the large arteries was consistently related to age, diastolic blood pressure, serum cholesterol, and height (inversely). Weak trends of association were also found with increasing serum glucose concentration, increasing cigarette use, and decreasing alcohol intake. Atherosclerosis scores in the small arteries were associated with diastolic blood pressure and serum triglyceride concentration. Analysis of dietary intake indicated that atherosclerosis scores were higher for men who reported low intakes of fat and animal protein and high intakes of vegetable protein and total carbohydrates. These patterns were consistent with similar findings on the incidence of clinical stroke in this cohort. Age-adjusted and -specific atherosclerosis scores from both the large and small arteries declined significantly during the period 1965-1983.

Risk factors related to ischemic and hemorrhagic cerebrovascular disease at autopsy: the Honolulu Heart Study.

This study of cerebrovascular lesions at autopsy among Hawaiian Japanese men identifies similar risks factors for cerebral infarction and hemorrhage that have been identified in a previous incidence study. Demonstrated differences were essentially the same whether subjects with these tissue changes were compared to men showing no central nervous system disease at autopsy or when they were compared with men still alive. Cerebral infarcts accompanied myocardial infarction (CHD) in 58% of autopsy cases and were associated with CHD risk factors (high serum cholesterol, hypertension, severe atherosclerosis of the coronary arteries and aorta). These associations did not persist when CHD cases were removed from the analysis, indicating there were two subsets of men with cerebral infarction. Hypertension was strongly associated with hemorrhagic disease, as were cigarette use and alcohol consumption.