c-JUN-like immunoreactivity in the CNS of the adult rat: basal and transynaptically induced expression of an immediate-early gene

An immunocytochemical study of dorsal root ganglia, spinal cord and medulla oblongata was performed with antisera against the c-jun proto-oncogene encoded protein. The c-JUN-like immunoreactivity was restricted to the cell nucleus. In the CNS of untreated rats a basal c-JUN-like immunoreactivity was present in the nuclei of two types of neurons: motor and autonomic. Labelled nuclei could be seen in many motoneurons of the ventral horn of the entire length of spinal cord and the lower medulla oblongata, as well as in the area of the nucleus hypoglossus, the dorsal motor nucleus of nucleus vagus, nucleus ambiguus, nucleus facialis, nucleus abducens and motor nucleus of nucleus trigeminus. Additionally, labelled nuclei were found in the preganglionic sympathetic and preganglionic parasympathetic cells of the nucleus intermediolateralis and nucleus intercalatus in the spinal cord. In the medulla oblongata we found a cluster of cells with c-JUN-like immunoreactivity in an area between the dorsomedial part of the oral nucleus spinalis trigeminalis and the lateral border of the knee of facial nerve. Additionally, a second cluster of c-JUN-like immunoreactivity cells was visible between the ventromedial part of the oral nucleus spinalis trigeminalis and the lateral border of the rostral nucleus facialis. Examination of the characteristics of all cell groups with a basal c-JUN-like immunoreactivity in the spinal cord and lower brainstem revealed an overlapping distribution with cholinergic cell groups. Basal c-JUN-like immunoreactivity was also seen in the dorsal root ganglion cells. We examined the factors which can effect the expression of the c-JUN protein. Maximal expression of c-JUN-like immunoreactivity was observed after electrical stimulation of primary afferents. Stimulation of sciatic nerve at a strength sufficient to recruit A delta- and C-fibres produced c-JUN-like immunoreactivity in many nuclei of the ipsilateral dorsal horn of the lumbar spinal cord. c-JUN-like immunoreactivity was first detectable at 30 min following the end of stimulation, reached a maximum after 1 h, remained unchanged for another 1 h and declined to the basal level after 16 h. The distribution of c-JUN-like immunoreactivity in the lumbar cord coincided with the region of termination of sciatic nociceptive afferents. Contralateral c-JUN-like immunoreactivity appeared after 4 h. After noxious mechanical stimulation of the plantar hindpaw c-JUN-like immunoreactivity occurred in the spinal area of termination of nociceptive afferents of the tibial nerve. Noxious stimulation did not provoke additional c-JUN-like immunoreactivity in dorsal root ganglia.(ABSTRACT TRUNCATED AT 400 WORDS)     

Genetic variants in a haplotype block spanning IDE are significantly associated with plasma Abeta42 levels and risk for Alzheimer disease

Risk for late onset Alzheimer disease (LOAD) and plasma amyloid beta levels (Abeta42; encoded by APP), an intermediate phenotype for LOAD, show linkage to chromosome 10q. Several strong candidate genes (VR22, PLAU, IDE) lie within the 1-lod support interval for linkage. Others have independently identified haplotypes in the chromosome 10q region harboring IDE that show highly significant association with intermediate AD phenotypes and with risk for AD. To pursue these associations, we analyzed the same haplotypes for association with plasma Abeta42 in 24 extended LOAD families and for association with LOAD in two independent case-control series. One series (MCR, 188 age-matched case-control pairs) did not show association (p=0.64) with the six haplotypes in the 276-kb region spanning three genes (IDE, KNSL1, and HHEX) previously shown to associate with LOAD. The other series (MCJ, 109 age-matched case-control pairs) showed significant (p=0.003) association with these haplotypes. In the MCJ series, the H4 (odds ratio [OR]=5.1, p=0.003) and H2(H7) haplotypes (OR=0.60, p=0.04) had the same effects previously reported. In this series, the H8 haplotype (OR=2.7, p=0.098) also had an effect similar as in one previous case control series but not in others. In the extended families, the H8 haplotype was associated with significantly elevated plasma Abeta42 (p=0.02). In addition, the H5(H10) haplotype, which is associated with reduced risk for AD in the other study is associated with reduced plasma Abeta42 (p=0.007) in our family series. These results provide strong evidence for pathogenic variant(s) in the 276-kb region harboring IDE that influence intermediate AD phenotypes and risk for AD.     

Lineage is an Epigenetic Modifier of QTL Influencing Behavioral Coping with Stress

A genome-wide scan was carried out on a segregating F2 population of rats derived from reciprocal intercrosses between two inbred strains of rats, Fisher 344 (F344) and Wistar Kyoto (WKY) that differ significantly in their behavioral coping responses to stress measured by the defensive burying (DB) test. The DB test measures differences in coping strategies by assaying an animals behavioral response to an immediate threat. We have previously identified three X-linked loci contributing to the phenotypic variance in behavioral coping. Here we report on six significant autosomal quantitative trait loci (QTL) related to different behaviors in the DB test:one for the number of shocks received, three for number of prod approaches, one for latency to bury, and one pleiotropic locus affecting both approach and latency. These QTL contributing to different aspects of coping behaviors show that the effect of genotype on phenotype is highly dependent on lineage. The WKY lineage was particularly influential, with five out of the six QTL affecting coping behavior only in rats of the WKY lineage, and one locus affecting only those in the F344 lineage. Thus, epigenetic factors, primarily of WKY origin, may significantly modulate the genetic contribution to variance in behavioral responses to stress in the DB test.     

Optimizing Efforts to Promote Mental Health on College and University Campuses: Recommendations to Facilitate Usage of Services,Resources, and Supports

The Journal of Behavioral Health Services & Research - Mental health has long been a challenge on college and university campuses. Though it has historically taken a back seat to physical...     

Physical activity and motor skill outcomes of a 10-week intervention for children with intellectual and developmental disabilities ages 4–13: A pilot study

BackgroundChildren with intellectual and developmental disabilities (IDD) often experience increased barriers to engaging in physical activity (PA) which can stem from lack of gross motor function (GMF) development. Intervening on GMF at an early age can create better opportunities for children with IDD to engage in regular PA. In turn, increased PA can improve health outcomes and increase social skills.ObjectiveThe primary objective of this pilot study was to explore the effectiveness of a community-based GMF-focused PA intervention for improving overall motor skills and PA for children with IDD.MethodsAll study participants (n = 24) engaged in 10 weeks of programming for 1 h each week. A convenience sample was utilized.ResultsResults indicated no statistically significant changes pre to post for motor skill scores. However, a visual analysis of mean changes showed a consistent pattern of increased scores from pre to post on most skills. Additionally, we found that a change in participant locomotor skills significantly predicted change in Moderate to Vigorous Physical Activity (MVPA), F (1,11) = 5.16, Adj R² = .26, p = .04.ConclusionsThese results suggest individualized attention on GMF may help to increase motor skills for children with IDD. This study adds to the small but growing amount of research examining the efficacy of community based adapted PA interventions. Further, study results should support continued exploration of effective approaches to address the motor delays experienced by children with IDD.     

Evaluation of an evidence-based guideline to reduce CT use in the assessment of blunt pediatric abdominal trauma

PurposeAbout half of pediatric blunt trauma patients undergo an abdominopelvic computed tomographic (CT) scan, while few of these require intervention for an intraabdominal injury. We evaluated the effectiveness of an evidence-based guideline for blunt abdominal trauma at a Level I pediatric trauma center.MethodsPediatric blunt trauma patients (n = 998) age 0–15 years who presented from the injury scene were evaluated over a 10 year period. After five years, we implemented our guideline in which the decision for CT was standardized based on mental status, abdominal examination, and laboratory results (alanine aminotransferase, aspartate aminotransferase, hemoglobin, urinalysis).ResultsThere were no differences in age, GCS, SIPA or ISS scores between the patients before or after guideline implementation. Nearly half of the patients (48.3%) underwent CT scan before guideline implementation compared to 36.7% after (p < 0.0002). There was no difference in ISS (p = 0.44) between CT scanned patients in either group. No statistical differences were found in rate of intervention (p = 0.20), length of stay (p = 0.65), or readmission rate (0.2%) before versus after guideline implementation. There were no missed injuries.ConclusionImplementation of an evidence-based clinical guideline for pediatric patients with blunt abdominal trauma decreases the rate of CT utilization while accurately identifying significant injuries.Level of evidenceIII.     

Balloon sphincteroplasty in pediatric laparoscopic common bile duct exploration

The management of choledocholithiasis in children and teenagers is often a two-procedure process with laparoscopic cholecystectomy (LC) and either pre- or post-operative endoscopic retrograde cholangiopancreatography (ERCP). The addition of laparoscopic common bile duct exploration (LCBDE) during LC can provide definitive treatment for choledocholithiasis during a single anesthetic event. In an effort to minimize sedation and radiation exposure from fluoroscopy, we have employed dilating balloons via a transcystic approach to stretch the sphincter of Oddi with subsequent ductal flushing. We describe the technique of balloon sphincteroplasty as a straightforward adjunct within the pediatric surgeon's skill set to manage choledocholithiasis during LC and our clinical experience.     

Tuberculosis infection and disease in South African adolescents with perinatally acquired HIV on antiretroviral therapy: a cohort study

IntroductionThere are limited data on Tuberculosis (TB) in adolescents with perinatally acquired HIV (APHIV). We examined the incidence and determinants of TB infection and disease in the Cape Town Adolescent Antiretroviral Cohort (CTAAC).MethodsYouth between nine and fourteen years on antiretroviral therapy (ART) for more than six months in public sector care, and age‐matched HIV‐negative adolescents, were enrolled between July 2013 through March 2015 and followed six‐monthly. Data were censored on 31 October 2018. Symptom screening, chest radiograph, viral load, CD4 count, QuantiFERON (QFT) and sputum for Xpert MTB/RIF, microscopy, culture and sensitivity were performed annually. TB infection was defined by a QFT of >0.35 IU/mL. TB diagnosis was defined as confirmed (culture or Xpert MTB/RIF positive) or unconfirmed (clinical diagnosis and started on TB treatment). Analyses examined the incidence and determinants of TB infection and disease.ResultsOverall 496 HIV+ and 103 HIV‐negative participants (median age at enrolment 12 years (interquartile range, IQR 10.6 to 13.3) were followed for a median of 3.1 years (IQR 3.0 to 3.4); 50% (298/599) were male. APHIV initiated ART at median age 4.4 years (IQR 2.1 to 7.6). At enrolment, 376/496 (76%) had HIV viral load <40 copies/mL, median CD4 count was 713 cells/mm³ and 179/559 (32%) were QFT+, with no difference by HIV status (APHIV 154/468, 33%; HIV negative 25/91, 27%; p = 0.31). The cumulative QFT+ prevalence was similar (APHIV 225/492, 46%; 95%CI 41% to 50%; HIV negative 44/98, 45%; 95% CI 35% to 55%; p = 0.88). APHIV had a higher incidence of all TB disease than HIV‐negative adolescents (2.2/100PY, 95% CI 1.6 to 3.1 vs. 0.3/100PY, 95% CI 0.04 to 2.2; IRR 7.36, 95% CI 1.01 to 53.55). The rate of bacteriologically confirmed TB in APHIV was 1.3/100 PY compared to 0.3/100PY for HIV‐negative adolescents, suggesting a fourfold increased risk of developing TB disease in APHIV despite access to ART. In addition, a positive QFT at enrolment was not predictive of TB in this population.ConclusionsHigh incidence rates of TB disease occur in APHIV despite similar QFT conversion rates to HIV‐negative adolescents. Strategies to prevent TB in this vulnerable group must be strengthened.     

Visual-vestibular interactions in postural control during the execution of a dynamic task

The purpose of this experiment was to determine the interaction between visual and vestibular information during the transition from quiet standing to the completion of a forward step. Six subjects were asked to take one step forward at the sound of an audio tone, with their eyes open or closed, and terminate the step in a standing position. During stimulation trials, galvanic vestibular stimulation (GVS) was delivered 1500 ms before the auditory cue. GVS was delivered at an intensity three-fold that of each subject's quiet stance threshold with either stimulus right, left or no stimulation. Force data were collected from three forceplates for the calculation of centre of pressure (CoP), and kinematic data were used to calculate centre of mass (CoM) and body trajectories. In quiet stance all subjects responded to the GVS perturbation by demonstrating upper body segment roll and whole body sway towards the anode electrode. Unexpectedly, in the presence of vision during quiet stance, the upper body roll response was not attenuated, even though the CoP sway patterns were reduced when vision was available. During the initiation phase of the step, despite ongoing GVS stimulation, there were no significant effects seen in CoM, CoP or upper body roll responses. During step execution, however, both CoM displacement and upper body roll demonstrated significant effects and both responses were significantly reduced when subjects' eyes were open. Analysis of the medio-lateral CoP integrals also indicated a strong stimulation effect between conditions late in the execution phase, which were largely attenuated with vision. The results suggest that the importance of visual and vestibular information varies depending on the phase of the task. In addition, the different integration between visual and vestibular input during quiet standing suggests a dual role for vestibular information. We propose that vestibular information in quiet standing has a role in maintaining whole body postural stability, as well as playing an integral role in the alignment of the body segments in preparation for proper movement execution. Vision was demonstrated to differentially attenuate these responses based on the phase of the task. Thus, visual and vestibular information appear to be integrated differently across the different phases of a forward-stepping task.