Cognitive, behavioral and psychological functioning of children and adults with conservatively managed metopic synostosis.

Children diagnosed with metopic synostosis (MS) commonly experience poor neuropsychological outcomes, with research suggesting that children whose MS is managed conservatively (without surgery) potentially having worse outcomes than their operated peers. However, studies of children whose MS was managed conservatively are scarce. This study therefore examined the cognitive, behavioral, and psychological functioning of children/adults with conservatively managed MS (N = 38) and compares their outcomes to individually matched healthy controls (N = 38) of the same age and sex (matched-pairs design) from the general community. Age-appropriate, validated assessments measuring general cognition, verbal and visuospatial ability, attention and working memory, executive functioning, behavior, depression, anxiety, and satisfaction with appearance were utilized. Group differences were estimated using linear regression for (a) the overall sample and (b) by broad developmental stages: 2&3 yrs; ≥6-≤17. Moderate to large negative effects (g = -0.38 to -1.30) were evident before controlling for socio-economic status (SES), with the MS group performing significantly worse on 8 out of the 10 cognitive domains (general cognition, visuospatial ability, working memory, information processing, executive functioning: semantic & initial letter verbal fluency, switching, inhibition+switching). However, only initial letter verbal fluency (g = -0.99) and switching (g = -1.19) remained significant after adjusting for SES. The MS group displayed more behavioral problems, although this was not significant. Depression, anxiety, and satisfaction with appearance did not differ between the groups. Regular monitoring of cognitive functioning, particularly executive functioning, should be undertaken for those with conservatively managed MS.

Cognitive, behavioral and psychological functioning in children with metopic synostosis: a meta-analysis examining the impact of surgical status.

Neurodevelopmental delays are known to occur in children with metopic synostosis, but it is presently unclear whether the cognitive, behavioral and psychological outcomes of children with metopic synostosis differ to those of their healthy peers. This meta-analysis consolidated data from 17 studies (published prior to August 2017) that examined the cognitive, behavioral and psychological outcomes of children (n = 666; aged ≤19 yrs) with metopic synostosis. Hedges'g (gw) effect sizes compared the outcomes of samples with metopic synostosis (unoperated, operated) to healthy controls or normative data and, where available, the prevalence of problems/disorders was calculated. Children with unoperated metopic synostosis performed significantly worse than their healthy peers on measures of: general cognition (gw = -.38), motor functioning, (gw = -.81), and verbal (gw = -.82) and visuospatial (gw = -.92) abilities. Children with operated metopic synostosis performed significantly worse on measures of motor functioning (gw = -.45), visuospatial skills (gw = -.32), attention (gw = -.50), executive functioning (gw = -.36), arithmetic ability (gw = -.37), and behavior (gw = -.34). Cognitive, behavioral, and psychological problems were prevalent, but variable. Overall, the cognitive, behavioral, and psychological outcomes of children with metopic synostosis are generally worse than their healthy peers, regardless of surgical status. However, research is sparse, samples small, controls are rarely recruited, and the severity of metopic synostosis often not stated. Nevertheless, the findings suggest that children with metopic synostosis are likely to experience a variety of negative outcomes and should therefore receive ongoing monitoring and support.

Impact of day-of-injury alcohol consumption on outcomes after traumatic brain injury: A meta-analysis.

Although a known risk factor for traumatic brain injury (TBI), alcohol has been found to both promote and protect against secondary brain damage. However, it is presently unclear whether the cognitive, psychological and medical/functional outcomes of adults who have consumed alcohol prior to sustaining a TBI differ from those who have not. This meta-analysis examined the outcomes of groups that differed in terms of their day-of-injury (DOI) blood alcohol levels (BALs) by comparing positive with zero BAL (BAL+/BAL-) and high with low BAL (BALhigh/BALlow) samples. The PubMed, PsycINFO, EMBASE, and Scopus databases were searched from inception until the end of March 2015. Hedge's g effects (continuous data) and odds ratios (categorical data) were calculated for 27 studies that compared either the outcomes of BAL+ and BAL- groups or BALhigh and BALlow groups. BAL+ was associated with significantly poorer cognitive outcomes (overall and on general tests) and higher levels of disability, and BALhigh was associated with shorter stays in intensive care. More generally, however, most effect sizes were small to low-moderate in size, non-significant and inconsistent in their direction. Although DOI alcohol consumption increases the risk of sustaining a TBI, it is not consistently associated with better or worse outcomes, other than subtle cognitive deficits; the source of which remains to be determined.

Traumatic Brain Injury and Depression in a Community-Based Sample: A Cohort Study Across the Adult Life Span.

OBJECTIVES: To determine whether self-reported traumatic brain injuries (TBIs) are associated with "cases" of clinically significant depression in the general community. To examine interactions between variables previously linked to depression after a TBI. SETTING: Population-based community study (Canberra and Queanbeyan, Australia). PARTICIPANTS AND DESIGN: Three age cohorts: young, middle-aged, and older adults (aged 20-24, 40-44, and 60-64 years at baseline) randomly selected from the electoral roll and followed across 3 waves (4 years apart). A total of 7397, 6621, and 6042 people provided their TBI history in waves 1 to 3. MEASURES: Lifetime (TBIlifetime: sustained at any time since birth), recent (TBIrecent: in the preceding 4 years), and multiple (TBImultiple: more than 1) TBIs, current depression, and known risk factors for depression (age, sex, marital/employment status, prior history of depression, medical conditions, recent life events, alcohol consumption, social support, physical activity). RESULTS: Generalized estimating equations demonstrated a significant association between sustaining a TBI and experiencing clinically significant depression (cases), even after controlling for multiple demographic and health/lifestyle factors. CONCLUSION: There is an enduring association between depression and TBI, suggesting that, following a TBI, individuals should be monitored and supported to optimize their long-term psychological health.

Anxiety and comorbid depression following traumatic brain injury in a community-based sample of young, middle-aged and older adults.

BACKGROUND: Anxiety is common following a traumatic brain injury (TBI), but who is most at risk, and to what extent, is not well understood. METHODS: Longitudinal data from a randomly-selected community sample (Wave 1: 7397, Wave 2: 6621 and Wave 3: 6042) comprising three adult cohorts (young: 20-24 years of age, middle-aged: 40-44, older: 60-64), were analysed. The association between TBI history, anxiety and comorbid depression was assessed, controlling for age, sex, marital/employment status, medical conditions, recent life events, alcohol consumption, social support and physical activity. RESULTS: Thirteen percent of the sample had sustained a TBI by Wave 3, 35% of whom had sustained multiple TBIs. Cross-sectional analyses revealed that clinically-significant anxiety was more common in people who had sustained a TBI. Longitudinal analyses demonstrated an increased risk of anxiety post-TBI, even after controlling for potential demographic, health and psychosocial confounds. Anxiety was more common than depression, although 10% of those with a TBI experienced comorbid anxiety/depression. LIMITATIONS: TBIs were not medically confirmed and anxiety and depression were only assessed every four years by self-report, rather than clinical interview. Sample attrition resulted in the retention of healthier individuals at each wave. CONCLUSIONS: TBIs are associated with a lifelong increased risk of experiencing clinically-significant anxiety, highlighting the chronic nature of TBI sequelae. Positive lifestyle changes (e.g., increasing physical activity, reducing alcohol consumption) may decrease the risk of anxiety problems in the early years after a TBI. Comorbid anxiety and depression was common, indicating that both should be monitored and treated.

Prevalence of anxiety following adult traumatic brain injury: A meta-analysis comparing measures, samples and postinjury intervals.

OBJECTIVE: Anxiety following a traumatic brain injury (TBI) is a common problem; however, disparate prevalence estimates limit the clinical utility of research. The purpose of the current study was to examine how differences in methodological variables and sample characteristics impact on the prevalence of anxiety. METHOD: Data from 41 studies that examined either the prevalence of generalized anxiety disorder (GAD) diagnoses or clinically significant "cases" of self-reported anxiety following adult, nonpenetrating TBI were analyzed, and the impact of diagnostic criteria, measure, postinjury interval and injury severity was evaluated. RESULTS: Overall, 11% of people were diagnosed with GAD and 37% reported clinically significant levels of anxiety following TBI. Prevalence estimates varied for different diagnostic criteria (range: 2%-19%), interview schedules (range: 2%-28%), and self-report measures (range: 36%-50%). GAD and "cases" of anxiety were most prevalent 2 to 5 years postinjury. The rates of GAD increased with injury severity (mild: 11%, severe 15%), but "cases" decreased (mild: 53%, severe: 38%), although neither difference was significant. CONCLUSIONS: Anxiety is common after a TBI and ongoing monitoring and treatment should be provided. Methodological and sample characteristics should be clear and well-defined, as differences across studies (e.g., how anxiety is conceptualized, which measure is used, time since injury, injury severity) impact prevalence rates.

Depression following adult, non-penetrating traumatic brain injury: a meta-analysis examining methodological variables and sample characteristics.

BACKGROUND: Depression is one of the most frequently reported psychological problems following TBI, however prevalence estimates vary widely. Methodological and sampling differences may explain some of this variability, but it is not known to what extent. METHODS: Data from 99 studies examining the prevalence of clinically diagnosed depression (MDD/dysthymia) and self-reports of depression (clinically significant cases or depression scale scores) following adult, non-penetrating TBI were analysed, taking into consideration diagnostic criteria, measure, post-injury interval, and injury severity. RESULTS: Overall, 27% of people were diagnosed with MDD/dysthymia following TBI and 38% reported clinically significant levels of depression when assessed with self-report scales. Estimates of MDD/dysthymia varied according to diagnostic criteria (ICD-10: 14%; DSM-IV: 25%; DSM-III: 47%) and injury severity (mild: 16%; severe: 30%). When self-report measures were used, the prevalence of clinically significant cases of depression differed between scales (HADS: 32%; CES-D: 48%) method of administration (phone: 26%; mail 46%), post-injury interval (range: 33-42%), and injury severity (mild: 64%; severe: 39%). CONCLUSION: Depression is very common after TBI and has the potential to impact on recovery and quality of life. However, the diagnostic criteria, measure, time post-injury and injury severity, all impact on prevalence rates and must therefore be considered for benchmarking purposes.

Mrc1 transduces signals of DNA replication stress to activate Rad53.

Cells experiencing DNA replication stress activate a response pathway that delays entry into mitosis and promotes DNA repair and completion of DNA replication. The protein kinases ScRad53 and SpCds1 (in baker's and fission yeast, respectively) are central to this pathway. We describe a conserved protein Mrc1, mediator of the replication checkpoint, required for activation of ScRad53 and SpCds1 during replication stress. mrc1 mutants are sensitive to hydroxyurea and have a checkpoint defect similar to rad53 and cds1 mutants. Mrc1 may be the replicative counterpart of Rad9 and Crb2, which are required for activating ScRad53 and Chk1 in response to DNA damage.

Mortality of employees in plants manufacturing 4,4'-bipyridyl.

A historical-prospective cohort study was conducted of 729 male employees of plants manufacturing 4,4'-bipyridyl. The cohort was studied because employment in some of the plants had been linked to malignant and nonmalignant skin lesions attributed to exposure to tarry by-products. The overall mortality experience of the cohort did not show any statistically significant findings. More-detailed analysis of subdivision of the cohort gave results that justified further inquiry into lung cancer incidence. A nested case-referent study did not indicate that any occupational factor other than employment in a bipyridyl plant was related to the incidence of lung cancer. The epidemiologic, toxicologic, and industrial hygiene information was assessed, and it was concluded that there was no evidence of a plausible occupational hazard of lung cancer to the bipyridyl workers, but that a follow-up of the cohort after an interval of five years should be undertaken.