Combining one-session treatment with a homework program including app-based technology to enhance the treatment of childhood specific phobias: A study protocol of a multicenter pragmatic randomized controlled trial.

Introduction: Childhood specific phobias are among the most common and earliest onset mental disorders with a lifetime prevalence of more than ten percent. Brief intensive cognitive behavioral therapy (CBT) programs such as the One-Session Treatment (OST) are found to be effective in the remission of the specific phobias following treatment, but there is still room for improvement. The goal of the current study is to examine whether the long-term efficacy of OST increases by using a homework program supported by an app specifically designed for children; the Kids Beat Anxiety (KibA) homework program. Methods: Children aged between 7 and 14 years with a specific phobia receive OST preceded by a three-week baseline phase to control for time-effects. Directly following OST, children are randomized to either a four-week homework period supported by an app (OST + app), or standard One-Session Treatment with a four-week homework period that is only supported by therapist instructions (OST-only). Primary outcome variables are diagnosis and severity of the specific phobia. Secondary outcomes include behavioral avoidance, self-reported fear, and functional impairment. Data will be analyzed based on intention-to-treat and per protocol samples using mixed-effects multilevel linear models. Ethics and dissemination: The current study was approved by the METC of the Academic Medical Center, Amsterdam, The Netherlands (number: NL72697.018.20) and the Ethical Committee of the Ruhr University, Bochum, Germany (number: 663). Results of this trial will be published in peer-reviewed journals. Trial registration: The study was pre-registered at the Dutch Trial Register, number: NL 9216.

Self-regulation as a resource for coping with developmental challenges during middle childhood and adolescence: the prospective longitudinal PIERYOUTH-study.

BACKGROUND: Self-regulation (SR) as the ability to regulate one's own physical state, emotions, cognitions, and behavior, is considered to play a pivotal role in the concurrent and subsequent mental and physical health of an individual. Although SR skills encompass numerous sub-facets, previous research has often focused on only one or a few of these sub-facets, and only rarely on adolescence. Therefore, little is known about the development of the sub-facets, their interplay, and their specific contributions to future developmental outcomes, particularly in adolescence. To fill these research gaps, this study aims to prospectively examine (1) the development of SR and (2) their influence on adolescent-specific developmental outcomes in a large community sample. METHODS/DESIGN: Based on previously collected data from the Potsdam Intrapersonal Developmental Risk (PIER) study with three measurement points, the present prospective, longitudinal study aims to add a fourth measurement point (PIERYOUTH). We aim to retain at least 1074 participants now between 16 and 23 years of the initially 1657 participants (6-11 years of age at the first measurement point in 2012/2013; 52.2% female). The study will continue to follow a multi-method (questionnaires, physiological assessments, performance-based computer tasks), multi-facet (assessing various domains of SR), and multi-rater (self-, parent-, and teacher-report) approach. In addition, a broad range of adolescent-specific developmental outcomes is considered. In doing so, we will cover the development of SR and relevant outcomes over the period of 10 years. In addition, we intend to conduct a fifth measurement point (given prolonged funding) to investigate development up to young adulthood. DISCUSSION: With its broad and multimethodological approach, PIERYOUTH aims to contribute to a deeper understanding of the development and role of various SR sub-facets from middle childhood to adolescence. The large sample size and low drop-out rates in the first three measurements points form a sound database for our present prospective research. Trial registration German Clinical Trials Register, registration number DRKS00030847.

The role of parental anxiety symptoms in the treatment of childhood social anxiety disorder.

The study investigated the role of parental anxiety symptoms in treatment outcomes for children with a primary social anxiety disorder compared to children with other primary anxiety disorders. Participants were 152 children between 7 and 18 years and their parents (146 mothers, 123 fathers). Anxiety was assessed pretreatment, posttreatment, and at three months and one year follow ups. There were no baseline differences in parental anxiety symptoms between the two groups. In both groups parental anxiety symptoms decreased from pretreatment to posttreatment, and only mothers' anxiety symptoms decreased further from posttreatment to the one year follow up. Parental anxiety symptoms before the treatment were not related to the being free of all anxiety diagnoses in the children at posttreatment. However, some indications were found for greater improvements during treatment when parents had higher anxiety symptoms before treatment. Changes in parental anxiety symptoms were found to be related to changes in child anxiety symptoms. This was not found for the total clinical severity of all inclusion anxiety disorders. This relation was visible independently in fathers or mothers, or in groups of children with a primary social anxiety disorder or with another primary anxiety disorder. In conclusion, we did not find clear indications that parental anxiety symptoms explain the differences in treatment outcomes for children with a primary social anxiety disorder compared to children with other primary anxiety disorders. More research with larger samples is needed to draw stronger conclusions.

Critical links between biodiversity and health in wild bee conservation.

Wild bee populations are declining due to human activities, such as land use change, which strongly affect the composition and diversity of available plants and food sources. The chemical composition of food (i.e., nutrition) in turn determines the health, resilience, and fitness of bees. For pollinators, however, the term 'health' is recent and is subject to debate, as is the interaction between nutrition and wild bee health. We define bee health as a multidimensional concept in a novel integrative framework linking bee biological traits (physiology, stoichiometry, and disease) and environmental factors (floral diversity and nutritional landscapes). Linking information on tolerated nutritional niches and health in different bee species will allow us to better predict their distribution and responses to environmental change, and thus support wild pollinator conservation.

Variation in nectar quality across 34 grassland plant species.

Floral nectar is considered the most important floral reward for attracting pollinators. It contains large amounts of carbohydrates besides variable concentrations of amino acids and thus represents an important food source for many pollinators. Its nutrient content and composition can, however, strongly vary within and between plant species. The factors driving this variation in nectar quality are still largely unclear. We investigated factors underlying interspecific variation in macronutrient composition of floral nectar in 34 different grassland plant species. Specifically, we tested for correlations between the phylogenetic relatedness and morphology of plants and the carbohydrate (C) and total amino acid (AA) composition and C:AA ratios of nectar. We found that compositions of carbohydrates and (essential) amino acids as well as C:AA ratios in nectar varied significantly within and between plant species. They showed no clear phylogenetic signal. Moreover, variation in carbohydrate composition was related to family-specific structural characteristics and combinations of morphological traits. Plants with nectar-exposing flowers, bowl- or parabolic-shaped flowers, as often found in the Apiaceae and Asteraceae, had nectar with higher proportions of hexoses, indicating a selective pressure to decelerate evaporation by increasing nectar osmolality. Our study suggests that variation in nectar nutrient composition is, among others, affected by family-specific combinations of morphological traits. However, even within species, variation in nectar quality is high. As nectar quality can strongly affect visitation patterns of pollinators and thus pollination success, this intra- and interspecific variation requires more studies to fully elucidate the underlying causes and the consequences for pollinator behaviour.

Inherited anxiety-related parent-infant dyads alter LHPA activity.

The pathogenesis of post-traumatic stress disorder (PTSD) is incompletely understood. We hypothesize that disruptions in mother-child relations may be a key contributor to development of PTSD. A normal and healthy separation-individuation process requires adaptations of self- and interactive contingency in both the mother and her child, especially in early childhood development. Anxious mothers are prone to overprotection, which may hinder the individuation process in their children. We examined long-term stress hormones and other stress markers in subjects three generations removed from the Holocaust, to assess the long-term consequences of inherited behavioral and physiological responses to prior stress and trauma. Jewish subjects who recalled overprotective parental behavior had higher hairsteroid-concentrations and dampened limbic-hypothalamic-pituitary-adrenal (LHPA) axis reactivity compared to German and Russian-German subjects with overprotective parents. We suggest that altered LHPA axis activity in maternally overprotected Jewish subjects may indicate a transmitted pathomechanism of "frustrated individuation" resulting from cross-generational anti-Semitic experiences. Thus measurements of hairsteroid-concentrations and parenting practices may have clinical value for diagnosis of PTSD. We propose that this apparent inherited adaptivity of LHPA axis activity could promote higher individual stress resistance, albeit with risk of an allostatic overload.

Interacting effects of pollination, water and nutrients on fruit tree performance.

Pollination is critical to fruit production, but the interactions of pollination with plant resources on a plant's reproductive and vegetative features are largely overlooked. We examined the influences of pollination, irrigation and fertilisation on the performance of almond, Prunus dulcis, in northern California. We used a full-factorial design to test for the effects of pollination limitation on fruit production and foliage variables of whole trees experiencing four resource treatments: (i) normal water and nutrients, (ii) reduced water, (iii) no nutrients, and (iv) reduced water and no nutrients. In each of these combinations, we applied three pollination treatments: hand-cross pollination, open-pollination and pollinator exclusion. Pollination strongly affected yield even under reduced water and no nutrient applications. Hand-cross pollination resulted in over 50% fruit set with small kernels, while open-pollinated flowers showed over 30% fruit set with moderate-sized kernels. Pollinator-excluded flowers had a maximum fruit set of 5%, with big and heavy kernels. Reduced water interacted with the open- and hand-cross pollination treatments, reducing yield more than in the pollinator exclusion treatment. The number of kernels negatively influenced the number of leaves, and reduced water and no nutrient applications interacted with the pollination treatments. Overall, our results indicate that the influences of pollination on fruit tree yield interact with the plant availability of nutrients and water and that excess pollination can reduce fruit quality and the production of leaves for photosynthesis. Such information is critical to understand how pollination influences fruit tree performance.

WITHDRAWN: Treatment outcome of visual feedback training in an adult patient with habitual toe walking.

Ahead of Print article withdrawn by publisher.

Differential effects of antiepileptic drugs on neonatal outcomes.

Offspring of women with epilepsy (WWE) on AEDs are at increased risks for major congenital malformations and reduced cognition. They may be at risk for other adverse neonatal outcomes. Women with epilepsy on carbamazepine (CBZ), lamotrigine (LTG), phenytoin (PHT), or valproate (VPA) monotherapy were enrolled in a prospective, observational, multicenter study of the neurodevelopmental effects of AEDs. The odds ratio for small for gestational age (SGA) was higher for VPA vs. PHT, VPA vs. LTG, and CBZ vs. PHT. Microcephaly rates were elevated to 12% for all newborns and at 12 months old, but normalized by age 24 months. Reduced Apgar scores occurred more frequently in the VPA and PHT groups at 1 min, but scores were near normal in all groups at 5 min. This study demonstrates increased risks for being born SGA in the VPA and CBZ groups, and transiently reduced Apgar scores in the VPA and PHT groups. Differential risks among the AEDs can help inform decisions about AED selection for women during childbearing years.

Postpartum headache.

Headache is a common puerperal complaint. A wide variety of factors can be involved, ranging from hormonal shifts, physiological changes, and peripartum procedures that may precipitate, worsen, or cause troublesome headache. The differential diagnosis of postpartum headache is broad and potentially daunting to the various clinicians caring for the postpartum patient. It often requires further neurological consultation or imaging to resolve. This review will focus on the main causes of postpartum headache, their incidence, and clinical presentation. Causes of postpartum headache that will be covered include benign primary headache disorders such as migraine and tension type headache as well as secondary headache disorders such as postdural puncture headache, stroke, and venous sinus thrombosis. A structured approach to headache evaluation in the postpartum patient will be presented to help differentiate the possible causes of headache.

Seasonal contrasts in the response of coffee ants to agroforestry shade-tree management.

In many tropical landscapes, agroforestry systems are the last forested ecosystems, providing shade, having higher humidity, mitigating potential droughts, and possessing more species than any other crop system. Here, we tested the hypothesis that higher levels of shade and associated humidity in agroforestry enhance coffee ant richness more during the dry than rainy season, comparing ant richness in 22 plots of three coffee agroforestry types in coastal Ecuador: simple-shade agroforests (intensively managed with low tree species diversity), complex-shade agroforests (extensively managed with intermediate tree species diversity) and abandoned coffee agroforests (abandoned for 10-15 yr and resembling secondary forests). Seasonality affected responses of ant richness but not composition to agroforestry management, in that most species were observed in abandoned coffee agroforests in the dry season. In the rainy season, however, most species were found in simple-shade agroforests, and complex agroforestry being intermediate. Foraging coffee ants species composition did not change differently according to agroforestry type and season. Results show that shade appears to be most important in the dry seasons, while a mosaic of different land-use types may provide adequate environmental conditions to ant species, maximizing landscape-wide richness throughout the year.

Linking deforestation scenarios to pollination services and economic returns in coffee agroforestry systems.

The ecological and economic consequences of rain forest conversion and fragmentation for biodiversity, ecosystem functioning, and ecosystem services like protection of soils, water retention, pollination, or biocontrol are poorly understood. In human-dominated tropical landscapes, forest remnants may provide ecosystem services and act as a source for beneficial organisms immigrating into adjacent annual and perennial agro-ecosystems. In this study, we use empirical data on the negative effects of increasing forest distance on both pollinator diversity and fruit set of coffee to estimate future changes in pollination services for different land use scenarios in Sulawesi, Indonesia. Spatially explicit land use simulations demonstrate that depending on the magnitude and location of ongoing forest conversion, pollination services are expected to decline continuously and thus directly reduce coffee yields by up to 18%, and net revenues per hectare up to 14% within the next two decades (compared to average yields of the year 2001). Currently, forests in the study area annually provide pollination services worth 46 Euros per hectare. However, our simulations also revealed a potential win-win constellation, in which ecological and economic values can be preserved, if patches of forests (or other natural vegetation) are maintained in the agricultural landscape, which could be a viable near future option for local farmers and regional land use planners.

Therapeutic efficacy of EGb761 (Gingko biloba extract) in a transgenic mouse model of amyotrophic lateral sclerosis.

EGb761 is a standardized extract of green Gingko biloba, which exerts protective effects against mitochondrial damage and oxidative stress. We examined whether oral administration of 0.022% or 0.045% EGb761 in the diet could impart neuroprotective effects in a transgenic mouse model (G93A) of amyotrophic lateral sclerosis (ALS). EGb761 significantly improved motor performance and survival, and protected against a loss of spinal-cord anterior motor horn neurons in male G93A mutant transgenic ALS mice, but not in littermate female mutant transgene mice. While EGb761 extended survival in littermate female G93A mice, significance was not reached. EGb761, however, significantly improved weight loss in both male and female transgenic ALS mice. These findings provide evidence for a gender-specific neuroprotective effect of EGb761 in a transgenic model of ALS and suggest that EGb761 may be a potential effective treatment in patients with ALS.

Transgenic ALS mice show increased vulnerability to the mitochondrial toxins MPTP and 3-nitropropionic acid.

The pathogenesis of neurodegenerative diseases may involve a genetic predisposition acting in concert with environmental toxins. To test this hypothesis we examined whether transgenic mice with the G93A mutation in Cu,Zn superoxide dismutase show increased vulnerability to either 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 3-nitropropionic acid (3-NP). Compared to littermate controls G93A transgenic mice showed a greater loss of striatal dopamine, DOPAC, and HVA at 50, 70, and 120 days of age following administration of MPTP; however, cell loss in the substantia nigra was not greater. The G93A transgenic mice showed significantly increased vulnerability to striatal lesions produced by 3-NP compared with littermate controls at 120 days of age. The finding that G93A mice show increased vulnerability to mitochondrial toxins further implicates mitochondrial dysfunction in the pathogenesis of neuronal death in these mice. The findings support the hypothesis that a genetic defect can increase susceptibility to environmental toxins and that this may play a role in the pathogenesis of neurodegenerative diseases.

Growth-related oncogene-alpha expression in human nasal polyps.

The cytokine growth-related oncogene-alpha (GRO-alpha) is a potent mediator of leukocyte recruitment and proliferation in inflammatory diseases. We hypothesized that GRO-alpha is produced in the inflammatory nasal polyp microenvironment. Evaluation of nasal polyps from 27 patients for distribution and content of GRO-alpha antigen, by use of immunohistochemical techniques and ELISA, revealed its presence in all 27 tissue samples. It was found predominantly within the eosinophils and neutrophils, with tissue levels ranging from 34 pg/mg total protein (TP) to 1746 pg/mg TP, with a mean value of 631 +/-98 pg/mg TP. Control tissues contained between 82 pg/mg TP and 316 pg/mg TP (mean 176+/-38 pg/mg TP). These results were statistically significant (P<0.03). Clinical correlations and statistical comparisons were calculated. These data suggest that GRO-alpha may be an important factor in the recruitment and activation of leukocytes in nasal polyposis, making it a potential target for therapeutic intervention.

Partial deficiency of manganese superoxide dismutase exacerbates a transgenic mouse model of amyotrophic lateral sclerosis.

The pathogenesis of neuronal cell death as a consequence of mutations in copper/zinc superoxide dismutase (SOD1) associated with familial amyotrophic lateral sclerosis may involve oxidative damage and mitochondrial dysfunction. We examined whether crossing transgenic mice with the G93A SOD1 mutation with transgenic mice with a partial depletion of manganese superoxide dismutase (SOD2) would affect the disease phenotype. Compared with G93A mice alone, the mice with partial deficiency of SOD2 and the G93A SOD1 mutation showed a significant decrease in survival and an exacerbation of motor deficits detected by rotorod testing. There was a significant exacerbation of loss of motor neurons and substantia nigra dopaminergic neurons in the G93A mice with a partial deficiency of SOD2 compared with G93A mice at 110 days. Microvesiculation of large motor neurons was more prominent in the G93A mice with a partial deficiency of SOD2 compared with G93A mice at 90 days. These findings provide further evidence that both oxidative damage and mitochondrial dysfunction may play a role in the pathogenesis of motor neuron death associated with mutations in SOD1.

Huntington aggregates may not predict neuronal death in Huntington's disease.

The mechanism by which polyglutamine expansion in Huntington's disease (HD) results in selective neuronal degeneration remains unclear. We previously reported that the immunohistochemical distribution of N-terminal huntingtin in HD does not correspond to the severity of neuropathology, such that significantly greater numbers of huntingtin aggregates are present within the cortex than in the striatum. We now show a dissociation between huntingtin aggregation and the selective pattern of striatal neuron loss observed in HD. Aggregate formation was predominantly observed in spared interneurons, with few or no aggregates found within vulnerable spiny striatal neurons. Multiple perikaryal aggregates were present in almost all cortical NADPH-diaphorase neurons and in approximately 50% of the spared NADPH-diaphorase striatal neurons from early grade HD cases. In severe grade HD patients, aggregates were more prominent as nuclear inclusions in NADPH-diaphorase neurons, with less perikaryal and neuropil aggregation. In contrast, nuclear or perikaryal huntingtin aggregates were present in less than 4% of the vulnerable calbindin striatal neurons in all HD cases. These findings support the hypothesis that polyglutamine aggregation may not be a predictor of cell loss. Rather than a harbinger of neuronal death, mutant huntingtin aggregation may be a cytoprotective mechanism against polyglutamine-induced neurotoxicity.

Creatine and cyclocreatine attenuate MPTP neurotoxicity.

Systemic administration of 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) produces parkinsonism in experimental animals by a mechanism involving impaired energy production. MPTP is converted by monoamine oxidase B to 1-methyl-4-phenylpyridinium (MPP+), which blocks complex I of the electron transport chain. Oral supplementation with creatine or cyclocreatine, which are substrates for creatine kinase, may increase phosphocreatine (PCr) or cyclophosphocreatine (PCCr) and buffer against ATP depletion and thereby exert neuroprotective effects. In the present study we found that oral supplementation with either creatine or cyclocreatine produced significant protection against MPTP-induced dopamine depletions in mice. Creatine protected against MPTP-induced loss of Nissl and tyrosine hydroxylase immunostained neurons in the substantia nigra. Creatine and cyclocreatine had no effects on the conversion of MPTP to MPP+ in vivo. These results further implicate metabolic dysfunction in MPTP neurotoxicity and suggest a novel therapeutic approach, which may have applicability for Parkinson's disease.

Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis.

Mitochondria are particularly vulnerable to oxidative stress, and mitochondrial swelling and vacuolization are among the earliest pathologic features found in two strains of transgenic amyotrophic lateral sclerosis (ALS) mice with SOD1 mutations. Mice with the G93A human SOD1 mutation have altered electron transport enzymes, and expression of the mutant enzyme in vitro results in a loss of mitochondrial membrane potential and elevated cytosolic calcium concentration. Mitochondrial dysfunction may lead to ATP depletion, which may contribute to cell death. If this is true, then buffering intracellular energy levels could exert neuroprotective effects. Creatine kinase and its substrates creatine and phosphocreatine constitute an intricate cellular energy buffering and transport system connecting sites of energy production (mitochondria) with sites of energy consumption, and creatine administration stabilizes the mitochondrial creatine kinase and inhibits opening of the mitochondrial transition pore. We found that oral administration of creatine produced a dose-dependent improvement in motor performance and extended survival in G93A transgenic mice, and it protected mice from loss of both motor neurons and substantia nigra neurons at 120 days of age. Creatine administration protected G93A transgenic mice from increases in biochemical indices of oxidative damage. Therefore, creatine administration may be a new therapeutic strategy for ALS.

Enterocutaneous fistula as a postoperative complication of laparoscopic inguinal hernia repair.

Trocar injuries to the small bowel during laparoscopic hernia repair are a rare complication, the most common complications being postoperative neuralgias, scrotal swelling, scrotal ecchymosis, and hematoma. A 15-year-old boy was admitted 5 days status-post transabdominal laparoscopic inguinal hernia repair of a symptomatic right pantaloon hernia, with signs and symptoms of a retrocecal abscess. Despite laparotic intervention and appendectomy, the next 2 years passed with almost daily, purulent, right lower quadrant wound drainage, in an otherwise asymptomatic patient. Superficial wound exploration and sinogram in 1996 revealed a sinus tract in direct communication with the small bowel. Elective laparotomy in December 1997 involved a successful resection of a 2.5-cm fistula with involved mesh, and the communicating small bowel through a midline incision, followed by a primary closure of the small-bowel opening. The patient has recovered without complications.