The bidirectional relationship between head injuries and conduct problems: longitudinal modelling of a population-based birth cohort study.

Childhood head injuries and conduct problems increase the risk of aggression and criminality and are well-known correlates. However, the direction and timing of their association and the role of their demographic risk factors remain unclear. This study investigates the bidirectional links between both from 3 to 17 years while revealing common and unique demographic risks. A total of 8,603 participants (50.2% female; 83% White ethnicity) from the Millennium Cohort Study were analysed at 6 timepoints from age 3 to 17. Conduct problems were parent-reported for ages 3 to 17 using the Strengths and Difficulties Questionnaire (SDQ) and head injuries at ages 3 to 14. A cross-lagged path model estimated the longitudinal bidirectional effects between the two whilst salient demographic risks were modelled cumulatively at three ecological levels (child, mother, and household). Conduct problems at age 5 promoted head injuries between 5 and 7 (Z = 0.07; SE = 0.03; 95% CI, 0.02-0.13), and head injuries at ages 7 to 11 promoted conduct problems at age 14 (ß = .0.06; SE = .0.03; 95% CI, 0.01-0.12). Head injuries were associated with direct child-level risk at age 3, whereas conduct problems were associated with direct risks from all ecological levels until 17 years. The findings suggest a sensitive period at 5-11 years for the bidirectional relationship shared between head injuries and conduct problems. They suggest that demographic risks for increased head injuries play an earlier role than they do for conduct problems. Both findings have implications for intervention timing.

Efficacy of neurostimulation across mental disorders: systematic review and meta-analysis of 208 randomized controlled trials.

Non-invasive brain stimulation (NIBS), including transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS), is a potentially effective treatment strategy for a number of mental conditions. However, no quantitative evidence synthesis of randomized controlled trials (RCTs) of TMS or tDCS using the same criteria including several mental conditions is available. Based on 208 RCTs identified in a systematic review, we conducted a series of random effects meta-analyses to assess the efficacy of NIBS, compared to sham, for core symptoms and cognitive functioning within a broad range of mental conditions. Outcomes included changes in core symptom severity and cognitive functioning from pre- to post-treatment. We found significant positive effects for several outcomes without significant heterogeneity including TMS for symptoms of generalized anxiety disorder (SMD = -1.8 (95% CI: -2.6 to -1), and tDCS for symptoms of substance use disorder (-0.73, -1.00 to -0.46). There was also significant effects for TMS in obsessive-compulsive disorder (-0.66, -0.91 to -0.41) and unipolar depression symptoms (-0.60, -0.78 to -0.42) but with significant heterogeneity. However, subgroup analyses based on stimulation site and number of treatment sessions revealed evidence of positive effects, without significant heterogeneity, for specific TMS stimulation protocols. For neurocognitive outcomes, there was only significant evidence, without significant heterogeneity, for tDCS for improving attention (-0.3, -0.55 to -0.05) and working memory (-0.38, -0.74 to -0.03) in individuals with schizophrenia. We concluded that TMS and tDCS can benefit individuals with a variety of mental conditions, significantly improving clinical dimensions, including cognitive deficits in schizophrenia which are poorly responsive to pharmacotherapy.

Linked head injury and conduct problem symptom pathways from early childhood to adolescence and their associated risks: Evidence from the millennium cohort study.

Conduct problems and head injuries increase the risk of delinquency and share a bidirectional association. However, how they link across development is unknown. The present study aimed to identify their linked developmental pathways and associated risk factors. Latent class analysis was modeled from Millennium Cohort Study data (n = 8,600) to identify linked pathways of conduct problem symptoms and head injuries. Head injuries were parent-reported from ages 3 to 14 and conduct problems from ages 3 to 17 using the Strengths and Difficulties Questionnaire (SDQ). Multinomial logistic regression then identified various risk factors associated with pathway membership. Four distinct pathways were identified. Most participants displayed low-level conduct problem symptoms and head injuries (n = 6,422; 74.7%). Three groups were characterized by clinically relevant levels of conduct problem symptoms and high-risk head injuries in childhood (n = 1,422; 16.5%), adolescence (n = 567; 6.6%), or persistent across development (n = 189; 2.2%). These clinically relevant pathways were associated with negative maternal parenting styles. These findings demonstrate how pathways of conduct problem symptoms are uniquely linked with distinct head injury pathways. Suggestions for general preventative intervention targets include early maternal negative parenting styles. Pathway-specific interventions are also required targeting cumulative risk at different ecological levels.

Adolescent delinquency following co-occurring childhood head injuries and conduct problem symptoms: findings from a UK longitudinal birth cohort.

Childhood conduct problems and head injuries share a bidirectional association, but how this affects the risk of adolescent delinquency is unknown. Due to their similar underlying mechanisms (i.e. increased impulsivity), this study aims to identify whether their co-occurrence increases the risk of adolescent delinquency. Data was obtained from 11,272 children at age 14 and 10,244 at age 17 years enrolled in the UK Millennium Cohort Study. Conduct problem symptoms (via the Strengths and Difficulties Questionnaire) and head injuries were parent reported from ages 3 to 14 years. Delinquency was self-reported at ages 14 and 17 including substance use, criminality, and antisocial behaviour. Incident rate ratios (IRR) were estimated for delinquency at ages 14 and 17 by childhood conduct problem and head injury status. Co-occurring head injuries and high conduct problem symptoms presented the greatest risk for overall delinquency and substance use at age 14 compared to those with the presence of one or neither (IRRs from 1.20 to 1.60). At age 17, conduct problems (with or without co-occurring head injuries) presented the greatest risk for overall delinquency, substance use, and antisocial behaviour. There was no evidence for an increased risk of delinquency at ages 14 or 17 following a head injury only. Whilst these findings suggest childhood head injuries alone do not increase the risk of adolescent delinquency, when co-occurring alongside high conduct problem symptoms there is a heightened earlier risk. These results provide further insight into adolescent delinquency and the outcomes of co-occurring childhood head injury and conduct problem symptoms.

The psychosocial impacts of vitiligo, psoriasis, and alopecia areata on pediatric patients.

Children and adolescents with chronic cutaneous conditions are at risk of experiencing adverse psychosocial effects such as anxiety, depression, and loneliness. The well-being of these children's families may also be impacted by their child's condition. It is important for the quality of life of patients and their families to better understand the psychosocial impact caused by pediatric dermatologic conditions and interventions that help mitigate these effects. This review summarizes the psychological impact of the common pediatric dermatological disorders, vitiligo, psoriasis, and alopecia areata, on children and their caregivers. Studies examining quality of life, psychiatric conditions, and other measures of psychosocial impact in children and caregivers, as well as those evaluating the effectiveness of interventions aimed at addressing psychosocial effects, were included. This review highlights the increased risk that children with these conditions have in experiencing adverse psychosocial effects including quality of life impairment, psychological pathology, and social stigmatization. In addition, the specific risk factors within this population that are associated with increased negative effect such as age and severity of disease are discussed. This review demonstrates a need for increased support of these patients and their families and additional research on the effectiveness of current interventions.

Differential Secretomes Of Processed Adipose Grafts, The Stromal Vascular Fraction And Adipose-derived Stem Cells.

There are multiple methods to prepare lipoaspirate for autologous fat transfer; however, graft retention remains unpredictable. The purpose of this study was to compare the cellular and protein composition of adipose grafts and the stromal vascular fraction (SVF) resulting from three common techniques to prepare adipose grafts. Adipose grafts were harvested from healthy donors and processed via three techniques: centrifugation (C), a single-filter (SF) device, a double-filtration (DF) system. Part of each graft was analyzed or further processed to isolate the SVF. Cell viability, surface markers, cytokine, and growth factors were compared between the graft and SVF as well as adipose derived stem cells (ASCs). Overall, we found variations across the three processing techniques and among the graft components (ASCs, SVF, fat). Cell viability within the grafts were similar (94.6%, 92.3%, and 93.6%; p=0.93). The trend was a greater percentage of ASCs from SF versus DF or centrifugation (6.95%, 4.63% and 1.93% respectively; p=0.06). Adipogenic markers (adiponectin, leptin) were similar among all three grafts (p=0.45). Markers of tissue remodeling were greatest in the SVF compared to fat and ASCs, regardless of processing technique. There was higher relative expression of MMP9 (2x), EMMPRIN (2.5x), endoglin (5x), and IL-8 (1.5x) in the SVF (p<0.005). Our study identified differences in cytokine expression in adipose grafts and the SVF, particularly in cytokines important in inflammation and wound healing. These secretomes may impact graft retention and fat necrosis and have potential implications in cell-assisted lipotransfer. There were no significant differences between the final products of any of the processing techniques.

Associated mortality risk of atypical antipsychotic medication in individuals with dementia.

BACKGROUND: Antipsychotic medications such as risperidone, olanzapine and aripiprazole are used to treat psychological and behavioural symptoms among dementia patients. Current evidence indicate prescription rates for antipsychotics vary and wider consensus to evaluate clinical epidemiological outcomes is limited. AIM: To investigate the potential impact of atypical antipsychotics on the mortality of patients with dementia. METHODS: A retrospective clinical cohort study was developed to review United Kingdom Clinical Record Interactive Search system based data between January 1, 2013 to December 31, 2017. A descriptive statistical method was used to analyse the data. Mini Mental State Examination (MMSE) scores were used to assess the severity and stage of disease progression. A cox proportional hazards model was developed to evaluate the relationship between survival following diagnosis and other variables. RESULTS: A total of 1692 patients were identified using natural language processing of which, 587 were prescribed olanzapine, quetiapine or risperidone (common group) whilst 893 (control group) were not prescribed any antipsychotics. Patients prescribed olanzapine showed an increased risk of death [hazard ratio (HR) = 1.32; 95% confidence interval (CI): 1.08-1.60; P < 0.01], as did those with risperidone (HR = 1.35; 95%CI: 1.18-1.54; P < 0.001). Patients prescribed quetiapine showed no significant association (HR = 1.09; 95%CI: 0.90-1.34; P = 0.38). Factors associated with a lower risk of death were: High MMSE score at diagnosis (HR = 0.72; 95%CI: 0.62-0.83; P < 0.001), identifying as female (HR = 0.73; 95%CI: 0.64-0.82; P < 0.001), and being of a White-British ethnic group (HR = 0.82; 95%CI: 0.72-0.94; P < 0.01). CONCLUSION: A significant mortality risk was identified among those prescribed olanzapine and risperidone which contradicts previous findings although the study designs used were different. Comprehensive research should be conducted to better assess clinical epidemiological outcomes associated with diagnosis and therapies to improve clinical management of these patients.

The Aichi Biodiversity Targets: achievements for marine conservation and priorities beyond 2020.

In 2010 the Conference of the Parties (COP) for the Convention on Biological Diversity revised and updated a Strategic Plan for Biodiversity 2011-2020, which included the Aichi Biodiversity Targets. Here a group of early career researchers mentored by senior scientists, convened as part of the 4th World Conference on Marine Biodiversity, reflects on the accomplishments and shortfalls under four of the Aichi Targets considered highly relevant to marine conservation: target 6 (sustainable fisheries), 11 (protection measures), 15 (ecosystem restoration and resilience) and 19 (knowledge, science and technology). We conclude that although progress has been made towards the targets, these have not been fully achieved for the marine environment by the 2020 deadline. The progress made, however, lays the foundations for further work beyond 2020 to work towards the 2050 Vision for Biodiversity. We identify key priorities that must be addressed to better enable marine biodiversity conservation efforts moving forward.

Early effects of 16O radiation on neuronal morphology and cognition in a murine model.

Astronauts exposed to high linear energy transfer radiation may experience cognitive injury. The pathogenesis of this injury is unknown but may involve glutamate receptors or modifications to dendritic structure and/or dendritic spine density and morphology. Glutamate is the major excitatory neurotransmitter in the central nervous system, where it acts on ionotropic and metabotropic glutamate receptors located at the presynaptic terminal and in the postsynaptic membrane at synapses in the hippocampus. Dendritic spines are sites of excitatory synaptic transmission, and changes in spine structure and dendrite morphology are thought to be morphological correlates of altered brain function associated with hippocampal-dependent learning and memory. The aim of the current study is to assess whether behavior, glutamate receptor gene expression, and dendritic structure in the hippocampus are altered in mice after early exposure to 16O radiation in mice. Two weeks post-irradiation, animals were tested for hippocampus-dependent cognitive performance in the Y-maze. During Y-maze testing, mice exposed to 0.1 Gy and 0.25 Gy radiation failed to distinguish the novel arm, spending approximately the same amount of time in all 3 arms during the retention trial. Exposure to 16O significantly reduced the expression of Nr1 and GluR1 in the hippocampus and modulated spine morphology in the dentate gyrus and cornu Ammon 1 within the hippocampus. The present data provide evidence that 16O radiation has early deleterious effects on mature neurons that are associated with hippocampal learning and memory.

Does obesity affect the position of seat belt loading in occupants involved in real-world motor vehicle collisions?

OBJECTIVE: Previous work has shown that the lap belt moves superior and forward compared to the bony pelvis as body mass index (BMI) increases. The goal of this project was to determine whether the location of lap belt loading is related to BMI for occupants who sustained real-world motor vehicle collisions (MVCs). METHODS: A national MVC database was queried for vehicle occupants over a 10-year period (2003-2012) who were at least 16 years old, restrained by a 3-point seat belt, sitting in the front row, and involved in a front-end collision with a change in velocity of at least 56 km/h. Cases were excluded if there was not an available computed tomography (CT) scan of the abdomen. CT scans were then analyzed using adipose enhancement of 3-dimensional reconstructions. Scans were assessed for the presence a radiographic seat belt sign (rSBS), or subcutaneous fat stranding due to seat belt loading. In scans in which the rSBS was present, anterior and superior displacement of rSBS from the anterior-superior iliac spine (ASIS) was measured bilaterally. This displacement was correlated with BMI and injury severity. RESULTS: The inclusion and exclusion criteria yielded 151 cases for analysis. An rSBS could definitively be identified in 55 cases. Cases in which occupants were older and had higher BMI were more likely to display an rSBS. There was a correlation between increasing BMI and anterior rSBS displacement (P <.01 and P <.01, right and left, respectively). There was no significant correlation between BMI and superior displacement of the rSBS (P =.46 and P =.33, right and left, respectively). When the data were examined in terms of relating increasing superior displacement of the lap belt with Injury Severity Scale (P =.34) and maximum Abbreviated Injury Score (AIS) injury severity (P =.63), there was also no significant correlation. CONCLUSION: The results from this study demonstrated that anterior displacement of the radiographic seat belt sign but not superior displacement increased with higher BMI. These results suggest that obesity may worsen horizontal position but not the vertical position of the lap belt loading during real-world frontal MVCs.

Changes in cognition and dendritic complexity following intrathecal methotrexate and cytarabine treatment in a juvenile murine model.

Acute lymphoblastic leukemia (ALL) is the most prevalent childhood cancer and accounts for 26.8% of cancer diagnoses among children, worldwide-approximately 3000 children each year. While advancements in treating ALL have led to a remission rate of more than 90%, many survivors experience adverse neurocognitive and/or neurobehavioral effects as a result of intrathecal chemotherapy. Methotrexate (MTX) is commonly administered with cytosine arabinoside (AraC, cytarabine) during intrathecal chemotherapy for ALL. To date, few studies exist that test the cognitive effects of intrathecal injections of MTX/AraC on juvenile populations. The purpose of our study was to investigate the combined effects of MTX/AraC on cognition and dendritic structure in the hippocampus in juvenile male mice. Twenty, 21-day-old male C57BL/6 mice were used in this study; 10 mice received intrathecal MTX/AraC treatment, and 10 were given intrathecal saline injections. Five weeks after injections, we tested the animals' hippocampus-dependent cognitive performance in the Morris water maze. After the first day of hidden-platform training, we observed that the mice that received MTX/AraC treatment showed signs of significant impairment in spatial memory retention. MTX/AraC treatment significantly compromised the dendritic architecture and reduced mushroom spine density in the dorsal ganglion (DG), CA1, and CA3 areas of the hippocampus. The present data provided evidence that MTX/AraC compromised the dendritic architecture and impaired hippocampal dependent cognition. This could provide insight into chemotherapy-induced cognitive decline in juvenile patients treated for ALL.

Effects of 1H + 16O Charged Particle Irradiation on Short-Term Memory and Hippocampal Physiology in a Murine Model.

Radiation from galactic cosmic rays (GCR) poses a significant health risk for deep-space flight crews. GCR are unique in their extremely high-energy particles. With current spacecraft shielding technology, some of the predominant particles astronauts would be exposed to are 1H + 16O. Radiation has been shown to cause cognitive deficits in mice. The hippocampus plays a key role in memory and cognitive tasks; it receives information from the cortex, undergoes dendritic-dependent processing and then relays information back to the cortex. In this study, we investigated the effects of combined 1H + 16O irradiation on cognition and dendritic structures in the hippocampus of adult male mice three months postirradiation. Six-month-old male C57BL/6 mice were irradiated first with 1H (0.5 Gy, 150 MeV/n) and 1 h later with 16O (0.1 Gy, 600 MeV/n) at the NASA Space Radiation Laboratory (Upton, NY). Three months after irradiation, animals were tested for hippocampus-dependent cognitive performance using the Y-maze. Upon sacrifice, molecular and morphological assessments were performed on hippocampal tissues. During Y-maze testing, the irradiated mice failed to distinguish the novel arm, spending approximately the same amount of time in all three arms during the retention trial relative to sham-treated controls. Irradiated animals also showed changes in expression of glutamate receptor subunits and synaptic density-associated proteins. 1H + 16O radiation compromised dendritic morphology in the cornu ammonis 1 and dentate gyrus within the hippocampus. These data indicate cognitive injuries due to 1H + 16O at three months postirradiation.

Late effects of 1H irradiation on hippocampal physiology.

NASA's Missions to Mars and beyond will expose flight crews to potentially dangerous levels of charged-particle radiation. Of all charged nuclei, 1H is the most abundant charged particle in both the galactic cosmic ray (GCR) and solar particle event (SPE) spectra. There are currently no functional spacecraft shielding materials that are able to mitigate the charged-particle radiation encountered in space. Recent studies have demonstrated cognitive injuries due to high-dose 1H exposures in rodents. Our study investigated the effects of 1H irradiation on neuronal morphology in the hippocampus of adult male mice. 6-month-old mice received whole-body exposure to 1H at 0.5 and 1 Gy (150 MeV/n; 0.35-0.55 Gy/min) at NASA's Space Radiation Laboratory in Upton, NY. At 9-months post-irradiation, we tested each animal's open-field exploratory performance. After sacrifice, we dissected the brains along the midsagittal plane, and then either fixed or dissected further and snap-froze them. Our data showed that exposure to 0.5 Gy or 1 Gy 1H significantly increased animals' anxiety behavior in open-field testing. Our micromorphometric analyses revealed significant decreases in mushroom spine density and dendrite morphology in the Dentate Gyrus, Cornu Ammonis 3 and 1 of the hippocampus, and lowered expression of synaptic markers. Our data suggest 1H radiation significantly increased exploration anxiety and modulated the dendritic spine and dendrite morphology of hippocampal neurons at a dose of 0.5 or 1 Gy.

Multinational comparative cross-sectional survey of views of medical students about acceptable terminology and subgroups in schizophrenia.

AIM: The aim of this study was to inform thinking around the terminology for 'schizophrenia' in different countries. OBJECTIVES: The objective of this study was to investigate: (1) whether medical students view alternative terminology (psychosis subgroups), derived from vulnerability-stress models of schizophrenia, as acceptable and less stigmatising than the term schizophrenia; (2) if there are differences in attitudes to the different terminology across countries with different cultures and (3) whether clinical training has an impact in reducing stigma. DESIGN: This is a cross-sectional survey that examined the attitudes of medical students towards schizophrenia and the alternative subgroups. SETTING: The study was conducted across eight sites: (1) University of Southampton, UK; (2) All India Institute of Medical Science, India; (3) Rowan University, USA; (4) Peshawar Medical College, Pakistan; (5) Capital Medical University, China; (6) College of Medicine and Medical sciences, Bahrain; (7) Queens University, Kingston, Canada and (8) University of Cape Town, South Africa. METHOD: This study extended an initial pilot conducted by the Royal College of Psychiatrists on the term schizophrenia and psychosis subgroups to assess whether the subgroup terminology might have an effect on the attitudes of a convenience sample of medical students from eight different countries and potentially play a role in reducing stigmatisation. RESULTS: 1873 medical students completed a questionnaire recording their attitudes to schizophrenia and the psychosis subgroups. A reduction in negative perceptions were found for the psychosis subgroups, especially for the stress sensitivity psychosis and anxiety psychosis subgroups. Negative perceptions were found for drug-related psychosis. Participants who had undergone clinical training had overall positive attitudes. Differences across different countries were found. CONCLUSION: The attitudes towards psychosis subgroups used in this study have shown mixed results and variation across countries. Further research is warranted to investigate acceptability of terminology. Methods of reducing stigma are discussed in line with the findings. ETHICS: The study received ethical approval from ERGO (Ethics and Research Governance Online; ID: 15972) and subsequently from the ethics committee at each site.

Inhibition of biofilm formation by Camelid single-domain antibodies against the flagellum of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a leading cause of hospital-acquired infections in patients with compromised host defense mechanisms, including burn wound victims. In addition to its intrinsic resistance against most antibiotics, P. aeruginosa has the ability to form biofilms adhering to biotic or abiotic surfaces. These factors make treatment of P. aeruginosa infections complicated and demand new therapies and drugs. The flagellum of P. aeruginosa plays an important role in cell-cell and cell-surface interactions during the first stage of biofilm formation. In this study, we describe the selection of monoclonal anti-flagellin single-domain antibodies (VHHs) derived from the Camelid heavy-chain antibody repertoire of a llama immunized with P. aeruginosa antigens. The anti-flagellin VHHs could be produced efficiently in Saccharomyces cerevisiae, and surface plasmon resonance experiments demonstrated that they have apparent affinities in the nanomolar range. Functional screens showed that the anti-flagellin VHHs are capable of inhibiting P. aeruginosa from swimming and that they prevent biofilm formation in an in vitro assay. These data open doors for the development of novel methods for the prevention of P. aeruginosa-related infections.

Reprint of "Inhibition of biofilm formation by Camelid single-domainantibodies against the flagellum of Pseudomonas aeruginosa".

Pseudomonas aeruginosa is a leading cause of hospital-acquired infections in patients with compromised host defense mechanisms, including burn wound victims. In addition to its intrinsic resistance against most antibiotics, P. aeruginosa has the ability to form biofilms adhering to biotic or abiotic surfaces. These factors make treatment of P. aeruginosa infections complicated and demand new therapies and drugs. The flagellum of P. aeruginosa plays an important role in cell­cell and cell­surface interactions during the first stage of biofilm formation. In this study, we describe the selection of monoclonal anti-flagellin single-domain antibodies (VHHs) derived from the Camelid heavy-chain antibody repertoire of a llama immunized with P. aeruginosa antigens. The anti-flagellin VHHs could be produced efficiently in Saccharomyces cerevisiae, and surface plasmon resonance experiments demonstrated that they have apparent affinities in the nanomolar range. Functional screens showed that the anti-flagellin VHHs are capable of inhibiting P. aeruginosa from swimming and that they prevent biofilm formation in an in vitro assay. These data open doors for the development of novel methods for the prevention of P. aeruginosa-related infections.