A feasibility randomized controlled trial of an individually delivered, peer support intervention to reduce the impact of psychosis stigma and discrimination for people with psychosis: the let's talk study.

Background: Stigma of mental health conditions hinders recovery and well-being. The Honest, Open, Proud (HOP) program shows promise in reducing stigma but there is uncertainty about the feasibility of a randomized trial to evaluate a peer-delivered, individual adaptation of HOP for psychosis (Let's Talk).

Methods: A multi-site, Prospective Randomized Open Blinded Evaluation (PROBE) design, feasibility randomised controlled trial (RCT) comparing the peer-delivered intervention (Let's Talk) to treatment as usual (TAU).

Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastoma.

Circular extrachromosomal DNA (ecDNA) in patient tumors is an important driver of oncogenic gene expression, evolution of drug resistance and poor patient outcomes. Applying computational methods for the detection and reconstruction of ecDNA across a retrospective cohort of 481 medulloblastoma tumors from 465 patients, we identify circular ecDNA in 82 patients (18%). Patients with ecDNA-positive medulloblastoma were more than twice as likely to relapse and three times as likely to die within 5 years of diagnosis.

Central Nervous System Distribution of Panobinostat in Preclinical Models to Guide Dosing for Pediatric Brain Tumors.

Achieving adequate exposure of the free therapeutic agent at the target is a critical determinant of efficacious chemotherapy. With this in mind, a major challenge in developing therapies for central nervous system (CNS) tumors is to overcome barriers to delivery, including the blood-brain barrier (BBB). Panobinostat is a nonselective pan-histone deacetylase inhibitor that is being tested in preclinical and clinical studies, including for the treatment of pediatric medulloblastoma, which has a propensity for leptomeningeal spread and diffuse midline glioma, which can infiltrate into supratentorial brain regions.

Honest, Open, Proud (HOP) for people with mental illness in Hong Kong: a randomized controlled trial.

Background: Self-stigma among people with mental illness is negatively associated with personal and clinical recovery. Due to the concealable nature of mental illness, people with mental illness experience constant struggles between concealment and disclosure. Disclosure of mental health challenges can potentially minimize negative impacts of self-stigma and enhance self-esteem and sense of empowerment.

Integrated genome and tissue engineering enables screening of cancer vulnerabilities in physiologically relevant perfusable ex vivo cultures.

Genetic screens are powerful tools for both resolving biological function and identifying potential therapeutic targets, but require physiologically accurate systems to glean biologically useful information. Here, we enable genetic screens in physiologically relevant ex vivo cancer tissue models by integrating CRISPR-Cas-based genome engineering and biofabrication technologies. We first present a novel method for generating perfusable tissue constructs, and validate its functionality by using it to generate three-dimensional perfusable dense cultures of cancer cell lines and sustain otherwise ex vivo unculturable patient-derived xenografts.

Factor analysis of the neurobehavioral symptom inventory in veterans with PTSD and no history of mild TBI.

It is well established that long-term postconcussive symptoms following a mild traumatic brain injury (mTBI) are associated with underlying physical, emotional, and behavioral conditions. The Neurobehavioral Symptom Inventory (NSI) is a measure used to assess neurobehavioral symptoms that can occur following a mTBI and has demonstrated a 3- or 4-factor structure in veterans. The present study aimed to investigate the factor structure of veterans with PTSD without a history of mTBI.

ChIPseqSpikeInFree: a ChIP-seq normalization approach to reveal global changes in histone modifications without spike-in.

Motivation: The traditional reads per million normalization method is inappropriate for the evaluation of ChIP-seq data when treatments or mutations have global effects. Changes in global levels of histone modifications can be detected with exogenous reference spike-in controls. However, most ChIP-seq studies overlook the normalization that must be corrected with spike-in.

Correction to: H3.3 K27M depletion increases differentiation and extends latency of diffuse intrinsic pontine glioma growth in vivo.

The original article can be found online.

H3.3 K27M depletion increases differentiation and extends latency of diffuse intrinsic pontine glioma growth in vivo.

Histone H3 K27M mutation is the defining molecular feature of the devastating pediatric brain tumor, diffuse intrinsic pontine glioma (DIPG). The prevalence of histone H3 K27M mutations indicates a critical role in DIPGs, but the contribution of the mutation to disease pathogenesis remains unclear. We show that knockdown of this mutation in DIPG xenografts restores K27M-dependent loss of H3K27me3 and delays tumor growth.

Insertional Mutagenesis Reveals Important Genetic Drivers of Central Nervous System Embryonal Tumors.

Medulloblastoma and central nervous system primitive neuroectodermal tumors (CNS-PNET) are aggressive, poorly differentiated brain tumors with limited effective therapies. Using () transposon mutagenesis, we identified novel genetic drivers of medulloblastoma and CNS-PNET. Cross-species gene expression analyses classified -driven tumors into distinct medulloblastoma and CNS-PNET subgroups, indicating they resemble human Sonic hedgehog and group 3 and 4 medulloblastoma and CNS neuroblastoma with activation.

Histone H3.3 K27M Accelerates Spontaneous Brainstem Glioma and Drives Restricted Changes in Bivalent Gene Expression.

Diffuse intrinsic pontine gliomas (DIPGs) are incurable childhood brainstem tumors with frequent histone H3 K27M mutations and recurrent alterations in PDGFRA and TP53. We generated genetically engineered inducible mice and showed that H3.3 K27M enhanced neural stem cell self-renewal while preserving regional identity.

Engineering Inducible Knock-In Mice to Model Oncogenic Brain Tumor Mutations from Endogenous Loci.

To maximize the physiological relevance of in vivo brain tumor mouse models designed to study the downstream effects of oncogenic mutations, it is important to express the mutated genes at appropriate levels, in relevant cell types, and in the proper developmental context. For recurrent mutations found in the heterozygous state in tumors, expression of the mutation from the endogenous locus is a more physiologically relevant recapitulation of the brain tumor genome. Here, we describe an approach to generate knock-in mice with an inducible mutation recombined into the endogenous locus.

The Impact of a Peer Navigator Program in Addressing the Health Needs of Latinos With Serious Mental Illness.

Objective: The impact of a peer navigator program (PNP) on efforts to address the health needs of Latinos with serious mental illness was examined in a randomized controlled trial.

Methods: Latinos with a serious mental illness (N=110) were randomly assigned to the PNP (integrated care with a peer navigator [PN]) or to a treatment-as-usual control group (integrated care without a PN) for one year. Data on service engagement (scheduled and received appointments) were assessed weekly, and self-reports of recovery, empowerment, and quality of life were collected at baseline and at four, eight, and 12 months.

PTEN Signaling in the Postnatal Perivascular Progenitor Niche Drives Medulloblastoma Formation.

Loss of the tumor suppressor gene PTEN exerts diverse outcomes on cancer in different developmental contexts. To gain insight into the effect of its loss on outcomes in the brain, we conditionally inactivated the murine Pten gene in neonatal neural stem/progenitor cells. Pten inactivation created an abnormal perivascular proliferative niche in the cerebellum that persisted in adult animals but did not progress to malignancy.

Key ingredients to contact-based stigma change: a cross-validation.

Objective: Contact-based antistigma programs seemingly have a larger and more sustained impact than educational strategies. Previous qualitative research of advocates with lived experiences yielded 32 key ingredients of contact-based programs comprising 5 categories. This study sought an independent sample's feedback of the 32 ingredients.

Production of homozygous transgenic rainbow trout with enhanced disease resistance.

Previous studies conducted in our laboratory showed that transgenic medaka expressing cecropin B transgenes exhibited resistant characteristic to fish bacterial pathogens, Pseudomonas fluorescens and Vibrio anguillarum. To confirm whether antimicrobial peptide gene will also exhibit anti-bacterial and anti-viral characteristics in aquaculture important fish species, we produced transgenic rainbow trout expressing cecropin P1 or a synthetic cecropin B analog, CF-17, transgene by sperm-mediated gene transfer method. About 30 % of fish recovered from electroporation were shown to carry the transgene as determined by polymerase chain reaction (PCR) amplification assay.

The California schedule of key ingredients for contact-based antistigma programs.

Objective: A major public health priority has been to eliminate stigma's egregious effects on life opportunities for people with mental illnesses. Research shows contact-based antistigma programs are among the most effective. Such findings call for clarity to define the components of consumer-directed antistigma programs.

Review: In vivo models for defining molecular subtypes of the primitive neuroectodermal tumor genome: current challenges and solutions.

Primitive neuroectodermal tumors (PNET) of the brain include medulloblastoma (MB) and central nervous system primitive neuroectodermal tumor (CNS PNET) subtypes, which share histological features yet differ at the genomic level and in clinical outcome. Delineation of the genetic anomalies between PNET subtypes is a current challenge for establishing effective targeted therapeutic strategies against these aggressive tumors. Current efforts have demonstrated that specific molecular pathways drive a subset of MB and CNS PNET, but the genetic basis for the deadliest forms of these tumors remains poorly understood and anecdotal.

The lineage-specific gene ponzr1 is essential for zebrafish pronephric and pharyngeal arch development.

The Homeobox (Hox) and Paired box (Pax) gene families are key determinants of animal body plans and organ structure. In particular, they function within regulatory networks that control organogenesis. How these conserved genes elicit differences in organ form and function in response to evolutionary pressures is incompletely understood.

Sino-American employer perspective about behavioral-driven health conditions: predictive analyses.

Objective: A large-scale quantitative study was conducted by stratified representative samples from Chicago (prototype of the United States; N = 293), Beijing (prototype of urbanized China; N = 302), and Hong Kong (prototype of East-meets-West culture; N = 284) to explore factors that might lead to their stigmatizing attitudes towards hiring individuals with (mental illness, alcohol abuse, drug abuse, and HIV/AIDS) and without (bone cancer) behavioral-driven health conditions.

Methods: Consented employers completed the Employer Survey pertaining to their attitudes towards specific health conditions, previous hiring experiences, resources, assets of applicants, and hiring concerns.

Results: The findings suggested that employers in Hong Kong and Beijing were more willing to hire individuals with alcohol abuse, whereas employers in Chicago were more willing to hire those with HIV/AIDS or bone cancer.

Chinese and American employers' perspectives regarding hiring people with behaviorally driven health conditions: the role of stigma.

Work opportunities for people with behaviorally driven health conditions such as HIV/AIDS, drug abuse, alcohol abuse, and psychosis are directly impacted by employer perspectives. To investigate this issue, we report findings from a mixed method design involving qualitative interviews followed by a quantitative survey of employers from Chicago (U.S.

Moesin1 and Ve-cadherin are required in endothelial cells during in vivo tubulogenesis.

Endothelial tubulogenesis is a crucial step in the formation of functional blood vessels during angiogenesis and vasculogenesis. Here, we use in vivo imaging of living zebrafish embryos expressing fluorescent fusion proteins of beta-Actin, alpha-Catenin, and the ERM family member Moesin1 (Moesin a), to define a novel cord hollowing process that occurs during the initial stages of tubulogenesis in intersegmental vessels (ISVs) in the embryo. We show that the primary lumen elongates along cell junctions between at least two endothelial cells during embryonic angiogenesis.

Sleeping beauty-mediated somatic mutagenesis implicates CSF1 in the formation of high-grade astrocytomas.

The Sleeping Beauty (SB) transposon system has been used as an insertional mutagenesis tool to identify novel cancer genes. To identify glioma-associated genes, we evaluated tumor formation in the brain tissue from 117 transgenic mice that had undergone constitutive SB-mediated transposition. Upon analysis, 21 samples (18%) contained neoplastic tissue with features of high-grade astrocytomas.

SELF-STIGMA AND COMING OUT ABOUT ONE'S MENTAL ILLNESS.

Self-stigma can undermine self-esteem and self-efficacy of people with serious mental illness. Coming out may be one way of handling self-stigma and it was expected that coming out would mediate the effects of self-stigma on quality of life. This study compares coming out to other approaches of controlling self-stigma.