Neuronal and Astrocyte Insulin-like Growth Factor-1 Signaling Differentially Modulates Ischemic Stroke Damage.

Ischemic stroke is a leading cause of death and disability, as therapeutic options for mitigating the long-term deficits precipitated by the event remain limited. Acute administration of the neuroendocrine modulator insulin-like growth factor-1 (IGF-1) attenuates ischemic stroke damage in preclinical models, and clinical studies suggest IGF-1 can reduce the risk of stroke and improve overall outcomes. The cellular mechanism by which IGF-1 exerts this protection is poorly defined, as all cells within the neurovascular unit express the IGF-1 receptor. We hypothesize that the functional regulation of both neurons and astrocytes by IGF-1 is critical in minimizing damage in ischemic stroke. To test this, we utilized inducible astrocyte-specific or neuron-specific transgenic mouse models to selectively reduce IGF-1R in the adult mouse brain prior to photothrombotic stroke. Acute changes in blood brain barrier permeability, microglial activation, systemic inflammation, and biochemical composition of the brain were assessed 3 hours following photothrombosis, and significant protection was observed in mice deficient in neuronal and astrocytic IGF-1R. When the extent of tissue damage and sensorimotor dysfunction was assessed for 3 days following stroke, only the neurological deficit score continued to show improvements, and the extent of improvement was enhanced with additional IGF-1 supplementation. Overall, results indicate that neuronal and astrocytic IGF-1 signaling influences stroke damage but IGF-1 signaling within these individual cell types is not required for minimizing tissue damage or behavioral outcome.

A Parenting Program to Reduce Disruptive Behavior in Hispanic Children with Acquired Brain Injury: A Randomized Controlled Trial Conducted in Mexico.

Children with acquired brain injury (ABI) are at risk of impairments in self-regulation and disruptive behavior. We aimed to investigate the effectiveness of the Signposts program to reduce disruptive behavior and improve self-regulation in Hispanic children with ABI, and reduce parental stress and improve parenting practices. Using a randomized controlled trial design, we assigned children (n = 71) and their parents to Signposts or generic telephone support. Blinded assessors conducted assessments at pre-intervention, immediately post-intervention, and at 3 months post-intervention. Signposts was effective in reducing dysfunctional parenting practices. Further, when analyzing participants at risk of behavioral disturbance (n = 46), Signposts was effective in reducing child disruptive behavior in the home environment and emotional self-regulation. No differences were found for parental stress, parent sense of competence, child disruptive behaviors at school, and child cognitive and behavioral self-regulation. The reduction in disruptive behavior was associated with the implementation of authoritative parenting practices (external regulation), and not associated with child self-regulation.

Helicobacter pylori pediatric infection changes FcεRI expression in dendritic cells and Treg profile in vivo and in vitro.

H. pylori infection shows an inverse relationship with allergies. Dendritic cells regulate mucosal immune responses including the induction of T regulatory cells which are fundamental in Helicobacter pylori-induced dampening of allergies. In this respect expression of high-affinity IgE receptor (FcεRI) has been associated with a regulatory dendritic cell profile. Therefore we aimed to evaluate possible mechanisms by which H. pylori infection might modify atopy in pediatric patients. Here we show that H. pylori-infected children exhibited both increased expression of FcεRI on peripheral myeloid and plasmacytoid dendritic cells and higher levels of Foxp3 and Latency Associated Peptide on T regulatory cells. Moreover, exposure to H. pylori drove increased FcεRI expression and IL-10 secretion by both pediatric H. pylori-exposed monocyte derived dendritic cells and T cells. Finally, we show a positive correlation between expression of FcεRI in circulating myeloid DCs and total Treg cells, suggesting that in children, H. pylori infection may have a modulating role in atopy, mediated by both altered surface expression of FcεRI on children's DC and an increased T regulatory cell profile.

How Do Parents Influence Child Disruptive Behavior After Acquired Brain Injury? Evidence From a Mediation Model and Path Analysis.

OBJECTIVES: Children with acquired brain injury (ABI) can present with disruptive behavior, which is often a consequence of injury and parent factors. Parent factors are associated with child disruptive behavior. Furthermore, disinhibition in the child also leads to disruptive behavior. However, it is unclear how these factors interact. We investigated whether parental factors influence child disruptive behavior following ABI and how these factors interact. METHODS: Parents of 77 children with ABI participated in the study. Parent factors (executive dysfunction, trait-anxiety), potential intervention targets (dysfunctional parenting practices, parental stress, child disinhibition), and child disruptive behavior were assessed. A hypothetical model based on the literature was tested using mediation and path analysis. RESULTS: Mediation analysis revealed that child disinhibition and dysfunctional parenting practices mediated the association of parent factors and child disruptive behavior. Parents' executive dysfunction mediated the association of dysfunctional parenting practices, parental stress and parent trait-anxiety. Parenting practices mediated the association of executive dysfunction and child disruptive behavior. Path analysis indices indicated good model adjustment. Comparative and Tucker-Lewis Index were >0.95, and the root mean square error of approximation was 0.059, with a chi-square of 0.25. CONCLUSIONS: A low level of parental trait-anxiety may be required to reduce dysfunctional parenting practices and child disinhibition. Impairments in child disinhibition can be exacerbated when parents present with high trait-anxiety. Child disinhibition is the major contributor of disruptive behavior reported by parents and teachers. The current study provides evidence of parent anxiety and child disinhibition as possible modifiable intervention targets for reducing child disruptive behavior. (JINS, 2019, 25, 237-248).

Parenting and the dysregulation profile predict executive functioning in children with acquired brain injury.

Background: Children with acquired brain injury (ABI) present with high rates of psychological disorders commonly accompanied by deficits in hot and cold executive functions (EFs). Impairments in EFs have been reported to precede mental health problems. Moreover, children who are vulnerable to developing mental health problems in adulthood frequently present with a dysregulation profile in childhood, characterized by impairments in cognitive, behavioral and emotional regulation. Objective: To identify profiles of behaviors associated with impairment in hot and cold EFs and compare injury factors, environmental stressors and dysregulation profile between them. Methods: A latent profile analysis was conducted with 77 children with ABI aged between 6 and 12. Injury factors, child IQ, environmental stressors and the dysregulation profile were compared between these behavioral profiles. Logistic regressions were conducted to predict profile membership. Results: Two profiles were identified: Profile M, with mild deficits (1-2 SD above the mean) in working memory and social skills, and profile C, presenting clinically significant deficits (2-3 SD above the mean) in shift, initiate, working memory, planning and social skills and mild deficits in inhibit, emotional control and task monitor. Proximal environmental stressors (dysfunctional parenting practices, parental stress, parent's executive dysfunction, anxiety-trait, and depressive symptoms) and dysregulation symptoms predicted profile membership, whereas injury factors, child IQ and distal environmental stressors did not. Conclusion: Following ABI, children with profile C are at risk of mental health problems and present with more proximal stressors. The dysregulation profile may be useful as a proxy for risk for later mental health problems in children with ABI.

A Systematic Review of Interventions for Hot and Cold Executive Functions in Children and Adolescents With Acquired Brain Injury.

Objective: We investigated interventions, which aimed to improve cold and hot executive functions (EFs) in children and adolescents with a diagnosis of acquired brain injury (ABI). Methods: The following electronic databases were searched: Medline, CINAHL, PsycINFO, and Pubmed. The database filters limited the search to articles published between 1990 and July 2017 in English or Spanish, including children and adolescents. Articles were read and classified according to the levels of evidence of the Australian National Health and Medical Research Council and the Downs and Black checklist was used for Measuring Study Quality. Results: Thirty studies are reported in this systematic review. Level of evidence, quality of the studies, characteristics of the participants, interventions implemented, and outcomes are described. Conclusions: The study of rehabilitation for executive dysfunction in children with ABI is emerging. Although few high-quality intervention studies exist in this area, which limits conclusions regarding intervention efficacy, results of existing studies suggest that education for parents may be an important component of intervention. Moreover, caregiver involvement may improve the effectiveness of hot EFs rehabilitation interventions, while high intervention session frequency may be important in improving cold EFs. Positive behavior supports and specific training based on a cognitive model provided some promising findings, which require further evaluation.

Feasibility and effectiveness of a parenting programme for Mexican parents of children with acquired brain injury-Case report.

BACKGROUND: Acquired brain injury (ABI) during childhood typically causes behaviour problems in the child and high levels of stress in the family. OBJECTIVES: (1) To investigate the feasibility and effectiveness of a parenting programme to: improve behaviour and self-regulation (SR) in Mexican children with ABI, enhance parenting skills, and decrease parental stress in parents of children with ABI; (2) to explore the impact of parent SR on child. METHODS: Case study design with four participants post-ABI, aged 7-12 years, recruited in Mexico City. A parenting programme (Signposts for Building Better Behaviour) was delivered and provided parents with strategies to manage child behaviour. Child behaviour, child self-regulation, parental stress and parenting practices were measured before, immediately post-intervention, and three months post-intervention. RESULTS: At immediate and three months post-intervention improvements in parenting skills, reduction in parental stress, and improvement in child behaviour were identified. CONCLUSIONS: The programme is feasible in a Mexican population and was effective in improving parenting skills and reducing stress in parents of children with ABI, as well as improving child behaviour and behavioural SR. These domains continue improving three months after the intervention. The improvements in challenging behaviour at home did not transfer to the school environment.

Heme Oxygenase-1 Modulates Human Respiratory Syncytial Virus Replication and Lung Pathogenesis during Infection.

Human respiratory syncytial virus (hRSV) is the leading cause of severe lower respiratory tract infections in children. The development of novel prophylactic and therapeutic antiviral drugs against hRSV is imperative to control the burden of disease in the susceptible population. In this study, we examined the effects of inducing the activity of the host enzyme heme oxygenase-1 (HO-1) on hRSV replication and pathogenesis on lung inflammation induced by this virus. Our results show that after hRSV infection, HO-1 induction with metalloporphyrin cobalt protoporphyrin IX significantly reduces the loss of body weight due to hRSV-induced disease. Further, HO-1 induction also decreased viral replication and lung inflammation, as evidenced by a reduced neutrophil infiltration into the airways, with diminished cytokine and chemokine production and reduced T cell function. Concomitantly, upon cobalt protoporphyrin IX treatment, there is a significant upregulation in the production of IFN-α/ß mRNAs in the lungs. Furthermore, similar antiviral and protective effects occur by inducing the expression of human HO-1 in MHC class II+ cells in transgenic mice. Finally, in vitro data suggest that HO-1 induction can modulate the susceptibility of cells, especially the airway epithelial cells, to hRSV infection.

Parenting program versus telephone support for Mexican parents of children with acquired brain injury: A blind randomized controlled trial.

INTRODUCTION: Acquired brain injury (ABI) during childhood typically causes behavior problems in the child and high levels of stress in the family. The aims of this study are: (1) to investigate the effectiveness and feasibility of a parenting intervention in improving behavior and self-regulation in Mexican children with ABI compared to telephone support; (2) to investigate the effectiveness and feasibility of a parenting intervention in improving parenting skills, parent self-efficacy and decreasing parental stress in parents of children with ABI compared to telephone support. Our secondary aims are (1) to explore the impact that parent characteristics have on the intervention outcomes; (2) to investigate if changes are maintained 3 months after the intervention. METHODS: The research design is a blind randomized controlled trial (RCT). Eligible participants include children with a diagnosis of ABI, between 6 and 12 years of age, and their parents. Sixty-six children and their parents will be randomly allocated to either a parenting program group or telephone support group. The parenting program involves six face-to-face weekly group sessions of 2.5 h each. Participants in the control group receive an information sheet with behavioral strategies, and six weekly phone calls, in which strategies to improve academic skills are provided. Children and their parents are evaluated by blind assessors before the intervention, immediately after the intervention and 3-months post-intervention. DISCUSSION: This study will be the first to evaluate the efficacy and feasibility of a parenting program for Mexican parents of children with ABI. TRIAL IDENTIFIER: ACTRN12617000360314.

Helicobacter pylori-Clarithromycin Resistance in Symptomatic Pediatric Patients in a High Prevalence Country.

INTRODUCTION: Failure to eradicate Helicobacter pylori despite antibiotic treatment is generally attributed to increasing clarithromycin resistance conferred by point mutations in the 23S-rRNA gene or metronidazole resistance attributed to rdxA gene (HP0954) deletion in patients. Scarce data for pediatric population are available from developing countries. OBJECTIVES: The aim of the present study was to determine the presence of A2142G/C and A2143G mutations in the 23S-rRNA gene and/or rdxA gene (HP0954) deletion in a group of symptomatic H pylori-infected children recruited from an area with high infection rate and risk of gastric cancer. PATIENTS AND METHODS: We recruited 118 patients referred for upper endoscopy for gastrointestinal symptoms. The presence of H pylori was determined by urease test and histological staining. The rdxA gene (HP0954) deletion, and 2142G/C and A2143G mutations were determined by polymerase chain reaction-restriction fragment length polymorphism. A subgroup of infected patients received a 14-day regimen of omeprazole, amoxicillin, and clarithromycin. The effectiveness of this regime was determined by stool antigen determination 8 weeks after treatment. RESULTS: About 21% of the analyzed infected patients showed mutation in the 23S-rRNA gene, with the A2143G transition as the more frequent mutation, and 2% of the patients showed rdxA gene (HP0954) deletion. After treatment, 25% of the patients continued to harbor the bacteria; of these, 67% carried the A2143G mutation. CONCLUSIONS: H pylori-infected pediatric patients from Chile show high prevalence of the mutation responsible for clarithromycin resistance. The failure to eradicate H pylori can be attributed to the presence of the A2143G mutation.

Elevated IL-3 and IL-12p40 levels in the lower airway of infants with RSV-induced bronchiolitis correlate with recurrent wheezing.

Respiratory Syncytial Virus (RSV) is the first cause of hospitalization due to bronchiolitis in infants. RSV bronchiolitis has been linked to asthma and recurrent wheezing, however the mechanisms behind this association have not been elucidated. Here, we evaluated the cytokine and chemokine profiles in the airways in infants with RSV bronchiolitis. Nasopharyngeal Aspirates (NPA) and Bronchoalveolar Lavage Fluids (BALF) from infants hospitalized due to RSV bronchiolitis and healthy controls were analyzed for cytokine and chemokine production. We observed elevated levels of Th2 cytokines (IL-3, IL-4, IL-10 and IL-13), pro-inflammatory cytokines and chemokines (IL-1ß, IL-6, TNF-ß, MCP-1/CCL2, MIP-1α/CCL3 and IL-8/CXCL8) in BALF from infants with RSV bronchiolitis, as compared to controls. We found a direct correlation of IL-3 and IL-12p40 levels with the development of recurrent wheezing later in life. These results suggest that IL-3 and IL-12p40 could be considered as molecular predictors for recurrent wheezing due to RSV infection.

Human metapneumovirus infection activates the TSLP pathway that drives excessive pulmonary inflammation and viral replication in mice.

Human metapneumovirus (hMPV) is a leading cause of acute respiratory tract infections in children and the elderly. The mechanism by which this virus triggers an inflammatory response still remains unknown. Here, we evaluated whether the thymic stromal lymphopoietin (TSLP) pathway contributes to lung inflammation upon hMPV infection. We found that hMPV infection promotes TSLP expression both in human airway epithelial cells and in the mouse lung. hMPV infection induced lung infiltration of OX40L(+) CD11b(+) DCs. Mice lacking the TSLP receptor deficient mice (tslpr(-/-) ) showed reduced lung inflammation and hMPV replication. These mice displayed a decreased number of neutrophils as well a reduction in levels of thymus and activation-regulated chemokine/CCL17, IL-5, IL-13, and TNF-α in the airways upon hMPV infection. Furthermore, a higher frequency of CD4(+) and CD8(+) T cells was found in tslpr(-/-) mice compared to WT mice, which could contribute to controlling viral spread. Depletion of neutrophils in WT and tslpr(-/-) mice decreased inflammation and hMPV replication. Remarkably, blockage of TSLP or OX40L with specific Abs reduced lung inflammation and viral replication following hMPV challenge in mice. Altogether, these results suggest that activation of the TSLP pathway is pivotal in the development of pulmonary pathology and pulmonary hMPV replication.

Lung cancer in HIV-infected patients.

Our objective was to determine the prevalence and characteristics of lung cancer (LC) in HIV patients and compare them with LC patients from the general population. All HIV patients diagnosed at three hospitals in Malaga (southern Spain) who developed LC during January 1989-June 2012 were reviewed. They were compared with a sample of patients with LC taken from the Pneumology and Oncology Department of the Hospital Virgen de le Victoria (Malaga) during the same period. Of the 4721 HIV patients (83% men) followed-up during the study period, 61 (1.29%) developed LC: 82% were men, mean age 48 years, all except two were smokers, 47.5% had a prior lung infection, and the median CD4 count was 237 cells/mm(3). Forty (65.5%) patients were on antiretroviral therapy at LC diagnosis (70% had an undetectable viral load). The HIV-negative group was older at diagnosis, contained fewer active smokers, had a greater frequency of the squamous cell carcinoma histological subtype and fewer cases of adenocarcinoma. Presentation was advanced in both groups and the median survival of HIV patients was three months. LC is a common tumour in HIV patients. It affects men and women equally, with a history of smoking and often a prior opportunistic lung disease. Affected patients are often immunosuppressed and have had an AIDS-related diagnosis.

Advances in understanding respiratory syncytial virus infection in airway epithelial cells and consequential effects on the immune response.

This article reviews aspects of respiratory syncytial virus (RSV) infection in airway epithelial cells (AECs), including cytopathogenesis, entry, replication and the induction of immune response to the virus, including a new role for thymic stromal lymphopoietin in RSV immunopathology.

Sensibilidad y especificidad del ultrasonido en el diagnóstico del hemoperitoneo en traumas cerrado del abdomen / Sensitivity and specificity of ultrasonography in the diagnosis of hemoperitoneum in blunt abdominal trauma

Se estudiaron durante 1 año en el Hospital Militar Central "Dr. Carlos J. Finlay", 50 pacientes con trauma cerrado de abdomen, cuyas edades estaban comprendidas entre 15 y 80 años. A todos se les realizó ultrasonido diagnóstico, a 31 de ellos punción abdominal; a 3, lavado peritoneal y 39 fueron operados de urgencia. Se comprobó que la sensibilidad y la especificidad del ultrasonido para el diagnóstico de sangramiento intraabdominal fue de 100 por ciento. La sensibilidad de la punción abdominal fue de 70,9 por ciento y hubo un falso positivo; la sangre abdominal produjo imagen ecolúcida en el 91 por ciento de los casos. Se comprobó la superioridad del ultrasonido en relación con la punción abdominal para establecer el diagnóstico del sangramiento que se produce en los traumas cerrados de abdomen. Se demostró la utilidad del ultrasonido en el diagnóstico de los sangramientos abdominales a veces ocultos (AU)

Sensibilidad y especificidad del ultrasonido en el diagnostico del hemoperitoneo en traumas cerrado del abdomen / Sensitivity and specificity of ultrasonography in the diagnosis of hemoperitoneum in blunt abdominal trauma

Se estudiaron durante 1 ano en el Hospital Militar Central "Dr. Carlos J. Finlay", 50 pacientes con trauma cerrado de abdomen, cuyas edades estaban comprendidas entre 15 y 80 anos. A todos se les realizo ultrasonido diagnostico, a 31 de ellos puncion abdominal; a 3, lavado peritoneal y 39 fueron operados de urgencia. Se comprobo que la sensibilidad y la especificidad del ultrasonido para el diagnostico de sangramiento intraabdominal fue de 100 por ciento. La sensibilidad de la puncion abdominal fue de 70,9 por ciento y hubo un falso positivo; la sangre abdominal produjo imagen ecolucida en el 91 por ciento de los casos. Se comprobo la superioridad del ultrasonido en relacion con la puncion abdominal para establecer el diagnostico del sangramiento que se produce en los traumas cerrados de abdomen. Se demostro la utilidad del ultrasonido en el diagnostico de los sangramientos abdominales a veces ocultos