Increased brain activation during working memory processing after pediatric mild traumatic brain injury (mTBI).

Purpose: The neural substrate of post-concussive symptoms following the initial injury period after mild traumatic brain injury (mTBI) in pediatric populations remains poorly elucidated. This study examined neuropsychological, behavioral, and brain functioning in adolescents post-mTBI to assess whether persistent differences were detectable up to a year post-injury. Methods: Nineteen adolescents (mean age 14.7 years) who experienced mTBI 3–12 months previously (mean 7.5 months) and 19 matched healthy controls (mean age 14.0 years) completed neuropsychological testing and an fMRI auditory-verbal N-back working memory task. Parents completed behavioral ratings. Results: No between-group differences were found for cognition, behavior, or N-back task performance, though the expected decreased accuracy and increased reaction time as task difficulty increased were apparent. However, the mTBI group showed significantly greater brain activation than controls during the most difficult working memory task condition. Conclusion: Greater working memory task-related activation was found in adolescents up to one year post-mTBI relative to controls, potentially indicating compensatory activation to support normal task performance. Differences in brain activation in the mTBI group so long after injury may indicate residual alterations in brain function much later than would be expected based on the typical pattern of natural recovery, which could have important clinical implications

Considerations for Studying Sex as a Biological Variable in Spinal Cord Injury

In response to NIH initiatives to investigate sex as a biological variable in preclinical animal studies, researchers have increased their focus on male and female differences in neurotrauma. Inclusion of both sexes when modeling neurotrauma is leading to the identification of novel areas for therapeutic and scientific exploitation. Here, we review the organizational and activational effects of sex hormones on recovery from injury and how these changes impact the long-term health of spinal cord injury (SCI) patients. When determining how sex affects SCI it remains imperative to expand outcomes beyond locomotor recovery and consider other complications plaguing the quality of life of patients with SCI. Interestingly, the SCI field predominately utilizes female rodents for basic science research which contrasts most other male-biased research fields. We discuss the unique caveats this creates to the translatability of preclinical research in the SCI field. We also review current clinical and preclinical data examining sex as biological variable in SCI. Further, we report how technical considerations such as housing, size, care management, and age, confound the interpretation of sex-specific effects in animal studies of SCI. We have uncovered novel findings regarding how age differentially affects mortality and injury-induced anemia in males and females after SCI, and further identified estrus cycle dysfunction in mice after injury. Emerging concepts underlying sexually dimorphic responses to therapy are also discussed. Through a combination of literature review and primary research observations we present a practical guide for considering and incorporating sex as biological variable in preclinical neurotrauma studies

Decreased cerebral blood flow in chronic pediatric mild TBI: an MRI perfusion study

We evaluated cerebral blood flow (CBF) in chronic pediatric mild traumatic brain injury (mTBI) using arterial spin labeling (ASL) magnetic resonance imaging perfusion. mTBI patients showed lower CBF than controls in bilateral frontotemporal regions, with no between-group cognitive differences. Findings suggest ASL may be useful to assess functional abnormalities in pediatric mTBI

Biodegradation of the Alkaline Cellulose Degradation Products Generated during Radioactive Waste Disposal.

The anoxic, alkaline hydrolysis of cellulosic materials generates a range of cellulose degradation products (CDP) including α and β forms of isosaccharinic acid (ISA) and is expected to occur in radioactive waste disposal sites receiving intermediate level radioactive wastes. The generation of ISA's is of particular relevance to the disposal of these wastes since they are able to form complexes with radioelements such as Pu enhancing their migration. This study demonstrates that microbial communities present in near-surface anoxic sediments are able to degrade CDP including both forms of ISA via iron reduction, sulphate reduction and methanogenesis, without any prior exposure to these substrates. No significant difference (n = 6, p = 0.118) in α and β ISA degradation rates were seen under either iron reducing, sulphate reducing or methanogenic conditions, giving an overall mean degradation rate of 4.7×10−2 hr−1 (SE±2.9×10−3). These results suggest that a radioactive waste disposal site is likely to be colonised by organisms able to degrade CDP and associated ISA's during the construction and operational phase of the facility

Applying a genetic risk score for prostate cancer to men with lower urinary tract symptoms in primary care to predict prostate cancer diagnosis : a cohort study in the UK Biobank

Background Prostate cancer is highly heritable, with >250 common variants associated in genome-wide association studies. It commonly presents with non-specific lower urinary tract symptoms that are frequently associated with benign conditions. Methods Cohort study using UK Biobank data linked to primary care records. Participants were men with a record showing a general practice consultation for a lower urinary tract symptom. The outcome measure was prostate cancer diagnosis within 2 years of consultation. The predictor was a genetic risk score of 269 genetic variants for prostate cancer. Results A genetic risk score (GRS) is associated with prostate cancer in symptomatic men (OR per SD increase = 2.12 [1.86-2.41] P = 3.5e-30). An integrated risk model including age and GRS applied to symptomatic men predicted prostate cancer (AUC 0.768 [0.739-0.796]). Prostate cancer incidence was 8.1% (6.7-9.7) in the highest risk quintile. In the lowest quintile, prostate cancer incidence was Conclusions This study is the first to apply GRS in primary care to improve the triage of symptomatic patients. Men with the lowest genetic risk of developing prostate cancer could safely avoid invasive investigation, whilst those identified with the greatest risk could be fast-tracked for further investigation. These results show that a GRS has potential application to improve the diagnostic pathway of symptomatic patients in primary care.Peer reviewe

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants

Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly with limited therapeutic options. Here, we report on a study of \u3e12 million variants including 163,714 directly genotyped, most rare, protein-altering variant. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P \u3c 5×10–8) distributed across 34 loci. While wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first signal specific to wet AMD, near MMP9 (difference-P = 4.1×10–10). Very rare coding variants (frequency \u3c 0.1%) in CFH, CFI, and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes

RCAN1 knockout and overexpression recapitulate an ensemble of rest-activity and circadian disruptions characteristic of Down syndrome, Alzheimer's disease, and normative aging

Regulator of calcineurin 1 (RCAN1) is overexpressed in Down syndrome (DS), but RCAN1 levels are also increased in Alzheimer&rsquo;s disease (AD) and normal aging. AD is highly comorbid among individuals with DS and is characterized in part by progressive neurodegeneration that resembles accelerated aging. Importantly, abnormal RCAN1 levels have been demonstrated to promote memory deficits and pathophysiology that appear symptomatic of DS, AD, and aging. Anomalous diurnal rest-activity patterns and circadian rhythm disruptions are also common in DS, AD, and aging and have been implicated in facilitating age-related cognitive decline and AD progression. However, no prior studies have assessed whether RCAN1 dysregulation may also promote the age-associated alteration of rest-activity profiles and circadian rhythms, which could in turn contribute to neurodegeneration in DS, AD, and aging. &nbsp;</p

Fire Promotes Pollinator Visitation: Implications for Ameliorating Declines of Pollination Services

Pollinators serve critical roles for the functioning of terrestrial ecosystems, and have an estimated annual value of over $150 billion for global agriculture. Mounting evidence from agricultural systems reveals that pollinators are declining in many regions of the world, and with a lack of information on whether pollinator communities in natural systems are following similar trends, identifying factors which support pollinator visitation and services are important for ameliorating the effects of the current global pollinator crisis. We investigated how fire affects resource structure and how that variation influences floral pollinator communities by comparing burn versus control treatments in a southeastern USA old-field system. We hypothesized and found a positive relationship between fire and plant density of a native forb, Verbesina alternifolia, as well as a significant difference in floral visitation of V. alternifolia between burn and control treatments. V. alternifolia density was 44% greater and floral visitation was 54% greater in burned treatments relative to control sites. When the density of V. alternifolia was experimentally reduced in the burn sites to equivalent densities observed in control sites, floral visitation in burned sites declined to rates found in control sites. Our results indicate that plant density is a proximal mechanism by which an imposed fire regime can indirectly impact floral visitation, suggesting its usefulness as a tool for management of pollination services. Although concerns surround the negative impacts of management, indirect positive effects may provide an important direction to explore for managing future ecological and conservation issues. Studies examining the interaction among resource concentration, plant apparency, and how fire affects the evolutionary consequences of altered patterns of floral visitation are overdue. DOI: 10.1371/journal.pone.007985