Investigating physiological symptoms associated with mental health symptoms in youth with cerebral palsy: An observational study.

Over 50 % of children and youth with cerebral palsy (CP) experience mental health challenges, with anxiety and depression most common. Youth with CP also experience several physiological symptoms such as fatigue, pain, sedentary lifestyle, and sleep disturbances that impact their daily living; however, little is known about the impact of these symptoms on mental health outcomes in these youth. This study addressed this gap and examined the individual and cumulative impacts of physiological symptoms on anxiety and depression symptoms in youth with CP. Forty youth with CP aged 8 to 18 years, and their caregiver, participated in this cross-sectional observational study. Pain, fatigue, anxiety, and depressive symptoms were measured using caregiver- and self-reported questionnaires and participants wore accelerometers for seven consecutive days, providing non-invasive physical activity and sleep pattern data. Youth with CP experienced substantial physiological symptoms and elevated anxiety and depression symptoms. Linear regression models determined that all physiological factors were predictive of caregiver-reported youth anxiety (R2 = 0.23) and youth depressive symptoms (R2 = 0.48). Fatigue, pain severity, sleep efficiency, and physical activity outcomes individually and cumulatively contributed to caregiver-reported youth anxiety and depression symptoms. These findings highlight the important role of physiological symptoms as potential risk factors and potential targets for intervention for mental health issues for in youth with CP.

Prevalence of co-occurring diagnoses in people exposed to alcohol prenatally: Findings from a meta-analysis.

BACKGROUND: Individuals with prenatal alcohol exposure (PAE) commonly experience co-occurring diagnoses, which are often overlooked and misdiagnosed and have detrimental impacts on accessing appropriate services. The prevalence of these co-occurring diagnoses varies widely in the existing literature and has not been examined in PAE without an FASD diagnosis. METHOD: A search was conducted in five databases and the reference sections of three review papers, finding a total of 2180 studies. 57 studies were included in the final analysis with a cumulative sample size of 29,644. Bayesian modeling was used to determine aggregate prevalence rates of co-occurring disorders and analyze potential moderators. RESULTS: 82 % of people with PAE had a co-occurring diagnosis. All disorders had a higher prevalence in individuals with PAE than the general population with attention deficit hyperactivity disorder, learning disorder, and intellectual disability (ID) being the most prevalent. Age, diagnostic status, and sex moderated the prevalence of multiple disorders. LIMITATIONS: While prevalence of disorders is crucial information, it does not provide a direct representation of daily functioning and available supports. Results should be interpreted in collaboration with more individualized research to provide the most comprehensive representation of the experience of individuals with PAE. CONCLUSIONS: Co-occurring diagnoses are extremely prevalent in people with PAE, with older individuals, females, and those diagnosed with FASD being most at risk for having a co-occurring disorder. These findings provide a more rigorous examination of the challenges faced by individuals with PAE than has existed in the literature, providing clinicians with information to ensure early identification and effective treatment of concerns to prevent lifelong challenges.

Arterial Spin-Labeling Perfusion Metrics in Pediatric Posterior Fossa Tumor Surgery.

BACKGROUND AND PURPOSE: Pediatric posterior fossa tumors often present with hydrocephalus; postoperatively, up to 25% of patients develop cerebellar mutism syndrome. Arterial spin-labeling is a noninvasive means of quantifying CBF and bolus arrival time. The aim of this study was to investigate how changes in perfusion metrics in children with posterior fossa tumors are modulated by cerebellar mutism syndrome and hydrocephalus requiring pre-resection CSF diversion. MATERIALS AND METHODS: Forty-four patients were prospectively scanned at 3 time points (preoperatively, postoperatively, and at 3-month follow-up) with single- and multi-inflow time arterial spin-labeling sequences. Regional analyses of CBF and bolus arrival time were conducted using coregistered anatomic parcellations. ANOVA and multivariable, linear mixed-effects modeling analysis approaches were used. The study was registered at clinicaltrials.gov (NCT03471026). RESULTS: CBF increased after tumor resection and at follow-up scanning (P = .045). Bolus arrival time decreased after tumor resection and at follow-up scanning (P = .018). Bolus arrival time was prolonged (P = .058) following the midline approach, compared with cerebellar hemispheric surgical approaches to posterior fossa tumors. Multivariable linear mixed-effects modeling showed that regional perfusion changes were more pronounced in the 6 children who presented with symptomatic obstructive hydrocephalus requiring pre-resection CSF diversion, with hydrocephalus lowering the baseline mean CBF by 20.5 (standard error, 6.27) mL/100g/min. Children diagnosed with cerebellar mutism syndrome (8/44, 18.2%) had significantly higher CBF at follow-up imaging than those who were not (P = .040), but no differences in pre- or postoperative perfusion parameters were seen. CONCLUSIONS: Multi-inflow time arterial spin-labeling shows promise as a noninvasive tool to evaluate cerebral perfusion in the setting of pediatric obstructive hydrocephalus and demonstrates increased CBF following resolution of cerebellar mutism syndrome.

I. EXECUTIVE CONTROL IN EARLY CHILDHOOD.

Executive control (EC) is a central construct in developmental science, although measurement limitations have hindered understanding of its nature and development in young children, relation to social risk, and prediction of important outcomes. Disentangling EC from the foundational cognitive abilities it regulates and that are inherently required for successful executive task completion (e.g., language, visual/spatial perception, and motor abilities) is particularly challenging at preschool age, when these foundational abilities are still developing and consequently differ substantially among children. A novel latent bifactor modeling approach delineated respective EC and foundational cognitive abilities components that undergird executive task performance in a socio demographically stratified sample of 388 preschoolers in a longitudinal, cohort-sequential study. The bifactor model revealed a developmental shift, where both EC and foundational cognitive abilities contributed uniquely to executive task performance at ages 4.5 and 5.25 years, but were not separable at ages 3 and 3.75. Contrary to the view that EC is vulnerable to socio-familial risk, the contributions of household financial and learning resources to executive task performance were not specific to EC but were via their relation to foundational cognitive abilities. EC, though, showed a unique, discriminant relation with hyperactive symptoms late in the preschool period, whereas foundational cognitive abilities did not predict specific dimensions of dysregulated behavior. These findings form the basis for a new, integrated approach to the measurement and conceptualization of EC, which includes dual consideration of the contributions of EC and foundational cognitive abilities to executive task performance, particularly in the developmental context of preschool.

ImmunoglobuliN in the Treatment of Encephalitis (IgNiTE): protocol for a multicentre randomised controlled trial.

INTRODUCTION: Infectious and immune-mediated encephalitides are important but under-recognised causes of morbidity and mortality in childhood, with a 7% death rate and up to 50% morbidity after prolonged follow-up. There is a theoretical basis for ameliorating the immune response with intravenous immunoglobulin (IVIG), which is supported by empirical evidence of a beneficial response following its use in the treatment of viral and autoimmune encephalitis. In immune-mediated encephalitis, IVIG is often used after a delay (by weeks in some cases), while diagnosis is confirmed. Wider use of IVIG in infectious encephalitis and earlier use in immune-mediated encephalitis could improve outcomes for these conditions. We describe the protocol for the first ever randomised control trial of IVIG treatment for children with all-cause encephalitis. METHODS AND ANALYSIS: 308 children (6 months to 16 years) with a diagnosis of acute/subacute encephalitis will be recruited in ∼30 UK hospitals and randomised to receive 2 doses (1 g/kg/dose) of either IVIG or matching placebo, in addition to standard treatment. Recruitment will be over a 42-month period and follow-up of each participant will be for 12 months post randomisation. The primary outcome is 'good recovery' (score of 2 or lower on the Glasgow Outcome Score Extended-paediatric version), at 12 months after randomisation. Additional secondary neurological measures will be collected at 4-6 weeks after discharge from acute care and at 6 and 12 months after randomisation. Safety, radiological, other autoimmune and tertiary outcomes will also be assessed. ETHICS AND DISSEMINATION: This trial has been approved by the UK National Research Ethics committee (South Central-Oxford A; REC 14/SC/1416). Current protocol: V4.0 (10/03/2016). The findings will be presented at national and international meetings and conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBERS: NCT02308982, EudraCT201400299735 and ISRCTN15791925; Pre-results.

What do we need to know about allogeneic hematopoietic stem cell transplant survivors?

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for over 70 benign and malignant hematologic and immunological processes. Over the past several decades, significant technological and post-transplant supportive advances have been made, resulting in a decrease in early transplant mortality and continued growth in the population of allo-HSCT survivors. With the expansion in the number of long-term survivors, as well as of those considering a transplant, the focus of transplant medicine has been shifted significantly to include a more prominent role for the care of the 'long-term' survivor. These patients have survived the acute critical phase of transplantation and have potentially achieved remission from their primary disease, yet allo-HSCT patients do not return to pre-transplant health status. For survivors >2 years removed, the time of transplant all-cause mortality is four- to nine-fold higher than age-matched peers within the general population. These patients represent a distinct, high-risk population that must be monitored for long-term transplant complications, including chronic GvHD (cGvHD), multi-organ dysfunctions and secondary malignancies. This article will review in a non-exhaustive manner, the approach to long-term care of an allo-HSCT recipient.

Developmental pathways from prenatal tobacco and stress exposure to behavioral disinhibition.

Prenatal tobacco exposure (PTE) and prenatal stress exposure (PSE) both have been linked to externalizing behavior, although their effects generally have been considered in isolation. Here, we aimed to characterize the joint or interactive roles of PTE and PSE in early developmental pathways to behavioral disinhibition, a profile of cognitive and behavioral under-control that presages severe externalizing behavior. As part of a prospective, longitudinal study, 296 children were assessed at a mean age of 5 years. Exposures were assessed via repeated interviews across the prenatal period and bioassays of cotinine were obtained. Behavioral disinhibition was assessed using temperament measures in infancy, performance-based executive control tasks and measures of disruptive and inattentive behavior. PSE was associated with a higher probability of difficult temperament in infancy. Each exposure independently predicted poorer executive control at age 5 years. Difficult temperament and executive control difficulties in turn predicted elevated levels of disruptive behavior, although links from PTE and PSE to parent-reported attention problems were less robust. Children who experienced these prenatal exposures in conjunction with higher postnatal stress exposure showed the lowest executive control and highest levels of disruptive behavior. Findings highlight the compounding adverse impact of PTE and PSE on children's behavioral trajectories. Given their high concordance, prenatal health campaigns should target these exposures in tandem.

Stylet penetration behaviors of Myzus persicae (Hemiptera: Aphididae) on four Ipomoea spp. infected or noninfected with sweet potato potyviruses.

Myzus persicae (Sulzer) is an efficient vector of potyviruses in sweet potato, Ipomoea batatas (L.). These potyviruses also infect members of the morning glory family Ipomoea cordatotriloba Dennstedt and Ipomoea hederacea Jacqin commonly found within or around sweet potato fields. Infection of sweet potato with potyviruses increases the intrinsic rate of increase of M. persicae. Thus, from the epidemiological stand point, virus infection can modify vector population dynamics, and therefore increase virus spread. To better understand this, stylet penetration behaviors of M. persicae on virus infected and noninfected sweet potato cvs. 'Beauregard' and 'Evangeline', as well as morning glory plants I. cordatotriloba and I. hederacea were monitored. Stylet penetration behaviors associated with nonpersistent virus transmission such as time to first intracellular puncture (potential drop), number of potential drops, duration of potential drop, duration of potential drop subphase II-3, and number of potential drops with subphase II-3 pulses were significantly increased on virus-infected compared with noninfected Beauregard, but greatly reduced on virus-infected compared with noninfected I. hederacea plants. Stylet penetration behaviors associated with host acceptance such as reduced nonprobing duration and nonprobing events were greater on virus-infected compared with noninfected Beauregard plants. In contrast, on Evangeline, I. cordatotriloba and I. hederacea stylet penetration behaviors by M. persicae indicate it had less preference for virus-infected compared with noninfected plants.

Very preterm birth: maternal experiences of the neonatal intensive care environment.

OBJECTIVE: Examine sources, predictors and child outcomes associated with neonatal intensive care unit (NICU)-related stress for mothers of infants born very preterm (VPT). STUDY DESIGN: Participants were 133 mothers of VPT infants admitted to a regional level-III NICU. At term equivalent, mothers completed the Parental Stressor Scale: NICU and were interviewed about their psychological well-being and family circumstances. Infant clinical data were also collected. At corrected age 4 years, 49 children were assessed for cognition, language and socio-emotional development. RESULT: Mothers reported moderate to low stress, with parental role alteration considered most stressful and parent-staff communications least stressful. Predictors of overall stress included maternal educational underachievement, stressful life events, postnatal depression and infant unsettled-irregular behavior. NICU-related stress was associated with child anxiety and poorer language development. CONCLUSION: Parental well-being is an important focus of care in the neonatal setting. Strategies are needed to optimize early engagement and reduce stress levels to assist improved child outcomes.

Prolonged febrile seizures cause reversible reductions in white matter integrity.

Prolonged febrile seizures (PFS) are the commonest cause of childhood status epilepticus and are believed to carry a risk of neuronal damage, in particular to the mesial temporal lobe. This study was designed to determine: i) the effect of prolonged febrile seizures on white matter and ii) the temporal evolution of any changes seen. 33 children were recruited 1 month following PFS and underwent diffusion tensor imaging (DTI) with repeat imaging at 6 and 12 months after the original episode of PFS. 18 age-matched healthy control subjects underwent similar investigations at a single time point. Tract-based spatial statistics (TBSS) was used to compare fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) between patients and controls on a voxel-wise basis within the white matter skeleton. Widespread reductions in FA along multiple white matter tracts were found at 1 and 6 months post-PFS, but these had resolved at 12 months. At one month post-PFS the main changes seen were reductions in AD but at 6 months these had predominantly changed to increases in RD. These widespread white matter changes have not previously been noted following PFS. There are many possible explanations, but one plausible hypothesis is that this represents a temporary halting of normal white matter development caused by the seizure, that then resumes and normalises in the majority of children.

Population dynamics of three aphid species (Hemiptera: Aphididae) on four Ipomoea spp. infected or noninfected with sweetpotato potyviruses.

Three aphid species, Aphis gossypii Glover and Myzus persicae (Sulzer) (efficient sweetpotato potyvirus vectors) and Rhopalosiphum padi (L.) (an inefficient vector), are commonly found in sweet potato, Ipomoea batatas (L.), in Louisiana. Field-grown sweet potatoes are naturally infected with several potyviruses: Sweet potato feathery mottle virus, Sweet potato virus G, and Sweet potato virus 2. Thus, these aphids commonly encounter virus-infected hosts. What is not known is how each of these aphids responds to sweet potato, either infected or virus-free. The objectives of this study were to 1) determine if these aphid species can colonize mixed virus-infected sweet potato 'Beauregard', and if so, 2) determine the effects of virus infection on the population dynamics of each aphid. A. gossypii failed to larviposit and R. padi deposited a single nymph that died within a day on mixed virus-infected Beauregard. M. persicae larviposited and colonized Beauregard and further life-table analyses were warranted. M. persicae had a significantly greater reproduction on sweet potato cultivars Beauregard and 'Evangeline' with mixed virus infection compared with noninfected plants. On morning glory species, Ipomoea cordatotriloba (Dennestedt) and Ipomoea hederacea (Jacquin), M. persicae had a significantly lower reproduction on Sweet potato feathery mottle virus-infected compared with noninfected plants.

The Role of Aphid Abundance, Species Diversity, and Virus Titer in the Spread of Sweetpotato Potyviruses in Louisiana and Mississippi.

Sweet potato feathery mottle virus (SPFMV), Sweet potato virus G (SPVG), and Sweet potato virus 2 (SPV2) are sweetpotato (Ipomoea batatas) potyviruses nonpersistently transmitted by aphids. Our objective was to determine how aphid abundance, aphid species diversity, and virus titers relate to the spread of SPFMV, SPVG, and SPV2 in Louisiana and Mississippi sweetpotato fields. The most abundant aphid species were Aphis gossypii, Myzus persicae, Rhopalosiphum padi, and Therioaphis trifolii. Aphids were captured during the entire crop cycle but virus infection of sentinel plants occurred mainly during the months of June to August. SPFMV was more commonly detected than SPVG or SPV2 in sentinel plants. Virus titers for SPFMV were higher in samples beginning in late June. Because significant aphid populations were present during April to June when virus titers were low in sweetpotato and there was very little virus infection of sentinel plants, low virus titers may have limited aphid acquisition and transmission opportunities. This is the first study to comprehensively examine aphid transmission of potyviruses in sweetpotato crops in the United States and includes the first report of R. maidis and R. padi as vectors of SPFMV, though they were less efficient than A. gossypii or M. persicae.

Endothelial cell protein C receptor-mediated redistribution and tissue-level accumulation of factor VIIa.

BACKGROUND: Recent studies show that activated factor VII (FVIIa) binds to the endothelial cell protein C receptor (EPCR) on the vascular endothelium; however, the importance of this interaction in hemostasis or pathophysiology is unknown. OBJECTIVE: The aim of the present study was to investigate the role of the FVIIa interaction with EPCR on the endothelium in mediating FVIIa transport from the circulation to extravascular tissues. METHODS: Wild-type, EPCR-deficient or ECPR-over-expressing mice were injected with human recombinant (r)FVIIa (120 µg kg(-1) body weight) via the tail vein. At varying time intervals after rFVIIa administration, blood and various tissues were collected to measure FVIIa antigen and activity levels. Tissue sections were analyzed by immunohistochemistry for FVIIa and EPCR. RESULTS: The data reveal that, after intravenous (i.v.) injection, rFVIIa rapidly disappears from the blood and associates with the endothelium in an EPCR-dependent manner. Immunohistochemical analyses revealed that the association of FVIIa with the endothelium was maximal at 30 min and thereafter progressively declined. The FVIIa association with the endothelium was undetectable at time points exceeding 24 h post-FVIIa administration. The levels of rFVIIa accumulated in tissue correlate with expression levels of EPCR in mice and FVIIa associated with tissues remained functionally active for periods of at least 7 days. CONCLUSIONS: The observation that an EPCR-dependent association of FVIIa with the endothelium is most pronounced soon after rFVIIa administration and subsequently declines temporally, combined with the retention of functionally active FVIIa in tissue homogenates for extended periods, indicates that FVIIa binding to EPCR on the endothelium facilitates the transport of FVIIa from circulation to extravascular tissues where TF resides.

Effect of Host Plant, Aphid Species, and Virus Infection Status on Transmission of Sweetpotato feathery mottle virus.

Sweetpotato feathery mottle virus (SPFMV) is a nonpersistently transmitted virus known to infect sweetpotato (Ipomoea batatas) and wild morning glory plants. SPFMV is vectored by various aphid species, among them the green peach aphid, Myzus persicae, and the cotton aphid, Aphis gossypii. Our objective was to determine whether differences in acquisition hosts (sweetpotato and morning glory), aphid species (M. persicae and A. gossypii), and infection status (single versus mixed infection) influenced transmission of SPFMV. SPFMV transmission from I. hederacea with a natural mixed infection by A. gossypii (39%) was significantly greater than in other host-virus combinations. Successful transmissions by A. gossypii were significantly greater compared with M. persicae in all host-virus combinations. Virus titers in source leaves were significantly greater in single- and mixed-infected I. hederacea and single-infected I. cordatotriloba compared with other host-virus combinations. There was a significant positive correlation between virus titer and transmission by both aphid species. These results suggest that, under controlled conditions, SPFMV is more readily transmitted from infected morning glory plants than from sweetpotato. Additionally, mixed-infected plants are better virus sources for transmission than single-infected, and A. gossypii is a more efficient vector than M. persicae under laboratory conditions.

Pattern recognition of MRSI data shows regions of glioma growth that agree with DTI markers of brain tumor infiltration.

Gliomas are the most common primary brain tumors and the majority are highly malignant, with one of the worst prognoses for patients. Gliomas are characterized by invasive growth into normal brain tissue that makes complete surgical resection and accurate radiotherapy planning extremely difficult. We have performed independent component analysis of magnetic resonance spectroscopy imaging data from human gliomas to segment brain tissue into tumor core, tumor infiltration, and normal brain, with confirmation by diffusion tensor imaging analysis. Our data are consistent with previous studies that compared anomalies in isotropic and anisotropic diffusion images to determine regions of potential glioma infiltration. We show that coefficients of independent components can be used to create colored images for easy visual identification of regions of infiltrative tumor growth.

Burkholderia glumae and B. gladioli Cause Bacterial Panicle Blight in Rice in the Southern United States.

Bacterial panicle blight (BPB) is among the three most limiting rice diseases in Louisiana and the southern United States. The identity and characterization of pathogens associated with this disease was unclear. This research details studies carried out on the pathogens causing BPB on rice in Louisiana and other rice producing southern states. Bacterial strains were isolated from BPB-infected sheath, panicle, or grain samples collected from rice fields in Louisiana, Arkansas, Texas, and Mississippi. In greenhouse inoculation tests, 292 of 364 strains were pathogenic on rice seedlings or panicles. Identification of strains in the pathogen complex by growth on S-PG medium, carbon source utilization profile (Biolog), cellular fatty acid analysis, and polymerase chain reaction (PCR) methods revealed that 76 and 5% of the strains were Burkholderia glumae and B. gladioli, respectively. The other strains have not been conclusively identified. Although strains of both species produced similar symptoms on rice, B. glumae strains were generally more aggressive and caused more severe symptoms on rice than B. gladioli. Virulent strains of both species produced toxoflavin in culture. The two species had similar growth responses to temperature, and optima ranged from 38 to 40°C for B. glumae and 35 to 37°C for B. gladioli. PCR was the most sensitive and accurate method tested for identifying the bacterial pathogens to the species level. The 16S rDNA gene and 16S-23S rDNA internal transcribed spacer (ITS) region sequences of the B. glumae and B. gladioli strains from rice showed more than 99% sequence homology with published sequences. A real-time PCR system was developed to detect and quantify this pathogen from infected seed lots. Our results clearly indicate that B. glumae and B. gladioli were the major pathogens causing BPB in the southern United States.