Arrhythmogenic right ventricular cardiomyopathy (ARVC) has a prevalence of at least 1 in 1000, is a leading cause of sudden cardiac death in people aged < or =35 years, and accounts for up to 10% of deaths from undiagnosed cardiac disease in the <65 age group. The classic form of the disease has an early predilection for the right ventricle, but recognition of left-dominant and biventricular subtypes has prompted proposal of the broader term arrhythmogenic cardiomyopathy. The clinical profile of the disease bridges the gap between the cardiomyopathies and inherited arrhythmia syndromes. The early "concealed" phase is characterized by propensity toward ventricular tachyarrhythmia in the setting of well-preserved morphology, histology, and ventricular function. As the disease progresses, however, myocyte loss, inflammation, and fibroadiposis become evident. Up to 40% of cases harbor rare variants in genes encoding components of the desmosome, specialized intercellular junctions that confer mechanical strength to cardiac and epithelial tissue, and may also participate in signaling networks. Phenotypic heterogeneity and the nonspecific nature of associated features complicate clinical diagnosis, which requires multipronged cardiovascular investigation rather than a single test. Development of a prospectively validated risk-stratification algorithm for the full disease spectrum remains the foremost clinical challenge.
To examine the prevalence of criminal thinking in mentally disordered offenders, incarcerated male (n = 265) and female (n = 149) offenders completed measures of psychiatric functioning and criminal thinking. Results indicated 92% of the participants were diagnosed with a serious mental illness, and mentally disordered offenders produced criminal thinking scores on the Psychological Inventory of Criminal Thinking Styles (PICTS) and Criminal Sentiments Scale-Modified (CSS-M) similar to that of non-mentally ill offenders. Collectively, results indicated the clinical presentation of mentally disordered offenders is similar to that of psychiatric patients and criminals. Implications are discussed with specific focus on the need for mental health professionals to treat co-occurring issues of mental illness and criminality in correctional mental health treatment programs.
The purpose of this paper is to cast a vision for the next generation of behavioral health and criminal justice interventions for persons with serious mental illnesses in the criminal justice system. The limitations of first generation interventions, including their primary focus on mental health treatment connection, are discussed. A person-place framework for understanding the complex factors that contribute to criminal justice involvement for this population is presented. We discuss practice and research recommendations for building more effective interventions to address both criminal justice and mental health outcomes.
SummaryInhibitors of poly(ADP-ribose) polymerase (PARP) have demonstrated efficacy in women with BRCA-mutant ovarian cancer. However, only 15%–20% of ovarian cancers harbor BRCA mutations, therefore additional therapies are required. Here, we show that a subset of ovarian cancer cell lines and ex vivo models derived from patient biopsies are sensitive to a poly(ADP-ribose) glycohydrolase (PARG) inhibitor. Sensitivity is due to underlying DNA replication vulnerabilities that cause persistent fork stalling and replication catastrophe. PARG inhibition is synthetic lethal with inhibition of DNA replication factors, allowing additional models to be sensitized by CHK1 inhibitors. Because PARG and PARP inhibitor sensitivity are mutually exclusive, our observations demonstrate that PARG inhibitors have therapeutic potential to complement PARP inhibitor strategies in the treatment of ovarian cancer.
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