De novo truncating mutation in Kinesin 17 associated with schizophrenia.

Background: Schizophrenia (SCZ) is one of the most disabling psychiatric disorders. It is thought to be due to a complex interplay between polygenic and various environmental risk factors, although recent reports on genomic copy number variations suggest that a fraction of the cases could result from variably penetrant de novo variants. The gene encoding the synaptic motor protein kinesin 17 (KIF17) involved in glutamatergic synapse is a candidate gene for SCZ.

Activation of caspase-3 in the skeletal muscle during haemodialysis.

Background And Objective: Muscle atrophy in end-stage renal disease (ESRD) may be due to the activation of apoptotic and proteolytic pathways. We hypothesized that activation of caspase-3 in the skeletal muscle mediates apoptosis and proteolysis during haemodialysis (HD).

Materials And Methods: Eight ESRD patients were studied before (pre-HD) and during HD and the findings were compared with those from six healthy volunteers.

A preliminary examination of the construct validity of the KABC-II in Ugandan children with a history of cerebral malaria.

Background: Several diseases and adverse conditions affect the cognitive development of children in Sub-Saharan African. There is need to assess these children to determine which abilities are affected and the severity of the damage so as to plan interventions accordingly. However most psychological tests developed in the West have not been validated in this region making it impossible to know whether they measure what they were intended to in African children.

Interactive links between theory of mind, peer victimization, and reactive and proactive aggression.

This study investigated the relation between theory of mind and reactive and proactive aggression, respectively, as well as the moderating role of peer victimization in this context. The 574 participants were drawn from a longitudinal study of twins. Theory of mind was assessed before school entry, when participants were 5 years old.

NeuroAIDS in Africa.

In July 2009, the Center for Mental Health Research on AIDS at the National Institute of Mental Health organized and supported the meeting "NeuroAIDS in Africa." This meeting was held in Cape Town, South Africa, and was affiliated with the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Presentations began with an overview of the epidemiology of HIV in sub-Saharan Africa, the molecular epidemiology of HIV, HIV-associated neurocognitive disorders (HANDs), and HAND treatment.

Intrinsic, identified, and controlled types of motivation for school subjects in young elementary school children.

Background: There are two approaches to the differential examination of school motivation. The first is to examine motivation towards specific school subjects (between school subject differentiation). The second is to examine school motivation as a multidimensional concept that varies in terms of not only intensity but also quality (within school subject differentiation).

HIV-subtype A is associated with poorer neuropsychological performance compared with subtype D in antiretroviral therapy-naive Ugandan children.

Background: HIV-subtype D is associated with more rapid disease progression and higher rates of dementia in Ugandan adults compared with HIV-subtype A. There are no data comparing neuropsychological function by HIV subtype in Ugandan children.

Design: One hundred and two HIV-infected antiretroviral therapy (ART) naive Ugandan children 6-12 years old (mean 8.

TLR9 polymorphisms are associated with altered IFN-gamma levels in children with cerebral malaria.

Toll-like receptor (TLR) polymorphisms have been associated with disease severity in malaria infection, but mechanisms for this association have not been characterized. The TLR2, 4, and 9 single nucleotide polymorphism (SNP) frequencies and serum interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) levels were assessed in Ugandan children with cerebral malaria (CM, N = 65) and uncomplicated malaria (UM, N = 52). The TLR9 C allele at -1237 and G allele at 1174 were strongly linked, and among children with CM, those with the C allele at -1237 or the G allele at 1174 had higher levels of IFN-gamma than those without these alleles (P = 0.

Maternal self-efficacy and hostile-reactive parenting from infancy to toddlerhood.

A longitudinal study of maternal self-efficacy (SE) and hostile-reactive parenting (HRP) was conducted with a community sample of 1836 mothers. Mothers completed questionnaires when their child was 4.5, 16.

The relationship between visual-spatial and auditory-verbal working memory span in Senegalese and Ugandan children.

Background: Using the Kaufman Assessment Battery for Children (K-ABC) Conant et al. (1999) observed that visual and auditory working memory (WM) span were independent in both younger and older children from DR Congo, but related in older American children and in Lao children. The present study evaluated whether visual and auditory WM span were independent in Ugandan and Senegalese children.

Monocyte derivatives promote angiogenesis and myocyte survival in a model of myocardial infarction.

In this study, we have investigated the hypothesis that previously reported beneficial effect of peripheral blood mononuclear cells cultured under angiogenic conditions on cardiovascular function following ischemia is not limited to EPCs but also to monocytes contained therein. We first purified and analyzed the phenotype and secretome of human and murine blood monocytes cultured under angiogenic conditions (named MDs for monocyte derivatives) and tested their effect in a mouse model of myocardial infarction (MI). FACS analysis of MDs shows that these cells express mature endothelial cell markers and that their proliferative capacity is virtually absent, consistent with their end-differentiated monocytic ontogeny.

Reliability of the Luganda version of the Child Behaviour Checklist in measuring behavioural problems after cerebral malaria.

Background: No measure of childhood behaviour has been validated in Uganda despite the documented risks to behaviour. Cerebral malaria in children poses a great risk to their behaviour, however behavioural outcomes after cerebral malaria have not been described in children. This study examined the reliability of the Luganda version of the Child Behaviour Checklist (CBCL) and described the behavioural outcomes of cerebral malaria in Ugandan children.

Socioeconomic predictors of cognition in Ugandan children: implications for community interventions.

Background: Several interventions to improve cognition in at risk children have been suggested. Identification of key variables predicting cognition is necessary to guide these interventions. This study was conducted to identify these variables in Ugandan children and guide such interventions.

Neuropsychological assessment of African children: evidence for a universal brain/behavior omnibus within a coconstructivist paradigm.

Cross-cultural neuropsychology with African and American children provides evidence of consistent deficit patterns in attention, working memory, and learning in children at risk from disease affecting brain function by means of similar pathophysiologic mechanisms (e.g., cerebral malaria (CM) and sickle-cell disease (SCD); HIV in African and American children).

Short nighttime sleep-duration and hyperactivity trajectories in early childhood.

Objectives: Our objectives were to investigate the developmental trajectories of nighttime sleep duration and hyperactivity over the preschool years and to identify the risk factors associated with short nighttime sleep duration and high hyperactivity scores.

Design, Setting, And Participants: Nighttime sleep duration and hyperactivity were measured yearly by questionnaires administered to mothers of 2057 children from age 1.5 to 5 years.

Diurnal cortisol secretion at home and in child care: a prospective study of 2-year-old toddlers.

Background: Previous studies indicate that children may experience disrupted cortisol secretion in child care. The extent to which this is a transient or long-term disruption is not known, as most studies have relied on cross-sectional designs, and age-heterogeneous small sample sizes. This study aims to (a) compare cortisol secretion measured at home and in child care at 2 and 3 years of age, (b) investigate cortisol changes from 2 to 3 years of age, (c) examine whether age at initiation of child care is associated with cortisol secretion, and (d) investigate whether cortisol secretion in child care is linked to behavioural problems.

CA125 (MUC16) tumor antigen selectively modulates the sensitivity of ovarian cancer cells to genotoxic drug-induced apoptosis.

Objective: Little is known about the biological functions of CA125/MUC16 tumor antigen. Here, we examined the role of CA125/MUC16 in regulating the sensitivity of epithelial ovarian carcinoma (EOC) cells to different drugs.

Methods: An endoplasmic reticulum targeted single-chain antibody (scFv) was used to down-regulate cell surface expression of CA125/MUC16 in NIH:OVCAR3 cells and the C-terminal domain (CTD) of MUC16 was ectopically expressed in CA125-negative SKOV3 cells.

Disregard for rules: the early development and predictors of a specific dimension of disruptive behavior disorders.

Background: Disregard for rules, an important dimension of oppositional defiant and conduct disorders, is frequent during early childhood, but the development of its chronic form has not been studied during this key socialization period. This study aimed to describe the developmental trajectories of disregard for rules during early childhood and identify prenatal and postnatal predictors for a high trajectory.

Methods: Participants were involved in a longitudinal study of a birth cohort followed yearly from 5 to 74 months of age (N = 1,942).

A granulocyte-macrophage colony-stimulating factor and interleukin-15 fusokine induces a regulatory B cell population with immune suppressive properties.

We have previously shown that a granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-15 (IL-15) 'fusokine' (GIFT15) exerts immune suppression via aberrant signaling through the IL-15 receptor on lymphomyeloid cells. We show here that ex vivo GIFT15 treatment of mouse splenocytes generates suppressive regulatory cells of B cell ontogeny (hereafter called GIFT15 B(reg) cells). Arising from CD19+ B cells, GIFT15 B(reg) cells express major histocompatibility complex class I (MHCI) and MHCII, surface IgM and IgD, and secrete IL-10, akin to previously described B10 and T2-MZP B(reg) cells, but lose expression of the transcription factor PAX5, coupled to upregulation of CD138 and reciprocal suppression of CD19.

Immediate neuropsychological and behavioral benefits of computerized cognitive rehabilitation in Ugandan pediatric cerebral malaria survivors.

Objective: Our earlier studies on Ugandan children surviving cerebral malaria showed cognitive deficits mainly in attention and memory. We now present the first study in sub-Saharan Africa to investigate the feasibility and potential benefits of computerized cognitive rehabilitation training on neuropsychological and behavioral functioning of children surviving cerebral malaria.

Methods: A randomized trial in which 65 children admitted 45 months earlier with cerebral malaria were recruited at Mulago Hospital, Kampala, Uganda.

Mesenchymal stromal cells cross-present soluble exogenous antigens as part of their antigen-presenting cell properties.

Recent studies involving bone marrow mesenchymal stromal cells (MSCs) demonstrated that interferon (IFN)-gamma stimulation induces major histocompatibility complex (MHC) class II-mediated antigen presentation in MSCs both in vitro and in vivo. Concordantly, we investigated the ability of MSCs to present extracellular antigen through their MHC class I molecules, a process known as cross-presentation. Using an in vitro antigen presentation assay, we demonstrated that murine MSCs can cross-present soluble ovalbumin (OVA) to naive CD8(+) T cells from OT-I mice.

Seizure activity and neurological sequelae in Ugandan children who have survived an episode of cerebral malaria.

Background: Seizures are a common presenting feature in children with cerebral malaria (CM) and neurologic deficits have been described in survivors of CM. However few prospective studies have described the frequency of seizure activity and neurologic deficits in survivors of CM over time.

Methods: Eighty-two children aged 3 to 12 years who survived an episode of CM were followed up and monitored for seizure activity and neurologic deficits at discharge, 3, 6 and 24 months.

An engineered GM-CSF-CCL2 fusokine is a potent inhibitor of CCR2-driven inflammation as demonstrated in a murine model of inflammatory arthritis.

CCR2 is a chemokine receptor widely expressed by lymphomyeloid cells involved in maladaptive autoimmune ailments. Therefore CCR2 is of great interest as a biological target for immune suppression due to its direct implication in autoimmune diseases such as rheumatoid arthritis. We have generated a novel fusion protein using GM-CSF and an N-terminal truncated version of MCP-1/CCL2 (6-76, GMME1) and investigated its utility as a CCR2-specific immune suppressor.

Characterization of Gaucher disease bone marrow mesenchymal stromal cells reveals an altered inflammatory secretome.

Gaucher disease causes pathologic skeletal changes that are not fully explained. Considering the important role of mesenchymal stromal cells (MSCs) in bone structural development and maintenance, we analyzed the cellular biochemistry of MSCs from an adult patient with Gaucher disease type 1 (N370S/L444P mutations). Gaucher MSCs possessed a low glucocerebrosidase activity and consequently had a 3-fold increase in cellular glucosylceramide.

Depression and anxiety symptoms: onset, developmental course and risk factors during early childhood.

Background: Depressive and anxiety disorders are among the top ten leading causes of disabilities. We know little, however, about the onset, developmental course and early risk factors for depressive and anxiety symptoms (DAS).

Objective: Model the developmental trajectories of DAS during early childhood and to identify risk factors for atypically high DAS.