Suicide Risk Assessment and Prevention: Challenges and Opportunities.

Despite increased access to mental health care for the previously uninsured and expanding evidence-based treatments for mood, anxiety, psychotic, and substance use disorders, suicide is on the rise in the United States. Since 1999, the age-adjusted suicide rate in the United States has increased 33%, from 10.5 per 100,000 standard population to 14.0. As of yet, there are no clinically available biomarkers, laboratory tests, or imaging to assist in diagnosis or the identification of the suicidal individual. Suicide risk assessment remains a high-stakes component of the psychiatric evaluation and can lead to overly restrictive management in the name of prevention or to inadequate intervention because of poor appreciation of the severity of risk. This article focuses primarily on suicide risk assessment and management as a critical first step to prevention, given the fact that more research is needed to identify precision treatments and effective suicide prevention strategies. Suicide risk assessment provides the clinical psychiatrist with an opportunity for therapeutic engagement with the ultimate goals of relieving suffering and preventing suicide.

Juvenile Sex Offenders.

Sexual offending by juveniles accounts for a sizable percentage of sexual offenses, especially against young children. In this article, recent research on female juvenile sex offenders (JSOs), risk factors for offending in juveniles, treatment, and the ways in which these youth may differ from general delinquents will be reviewed. Most JSOs do not go on to develop paraphilic disorders or to commit sex offenses during adulthood, and as a group, they are more similar to nonsexual offending juvenile delinquents than to adult sex offenders. Recent research has elucidated some differences between youth who commit sex offenses and general delinquents in the areas of atypical sexual interests, the use of pornography, and early sexual victimization during childhood.

Juvenile Sex Offenders.

Public policy has tended to treat juvenile sex offenders (JSOs) as adult sex offenders in waiting, despite research that contradicts this notion. Although as a group, JSOs are more similar to general delinquents than to adult sex offenders, atypical sexual interests and sexual victimization during childhood may be a pathway for sexual offending that differentiates some JSOs from their nonsexually delinquent peers. Developmental considerations must be considered in risk assessment evaluations of these youth. This article reviews theories of sexual offending in youth, risk factors for juvenile offending and reoffending, psychopathology in JSOs, risk assessment, and treatment.

NC-mediated nucleolar localization of retroviral gag proteins.

The assembly and release of retrovirus particles from the cell membrane is directed by the Gag polyprotein. The Gag protein of Rous sarcoma virus (RSV) traffics through the nucleus prior to plasma membrane localization. We previously reported that nuclear localization of RSV Gag is linked to efficient packaging of viral genomic RNA, however the intranuclear activities of RSV Gag are not well understood. To gain insight into the properties of the RSV Gag protein within the nucleus, we examined the subnuclear localization and dynamic trafficking of RSV Gag. Restriction of RSV Gag to the nucleus by mutating its nuclear export signal (NES) in the p10 domain or interfering with CRM1-mediated nuclear export of Gag by leptomycin B (LMB) treatment led to the accumulation of Gag in nucleoli and discrete nucleoplasmic foci. Retention of RSV Gag in nucleoli was reduced with cis-expression of the 5' untranslated RU5 region of the viral RNA genome, suggesting the psi (Ψ) packaging signal may alter the subnuclear localization of Gag. Fluorescence recovery after photobleaching (FRAP) demonstrated that the nucleolar fraction of Gag was highly mobile, indicating that there was rapid exchange with Gag proteins in the nucleoplasm. RSV Gag is targeted to nucleoli by a nucleolar localization signal (NoLS) in the NC domain, and similarly, the human immunodeficiency virus type 1 (HIV-1) NC protein also contains an NoLS consisting of basic residues. Interestingly, co-expression of HIV-1 NC or Rev with HIV-1 Gag resulted in accumulation of Gag in nucleoli. Moreover, a subpopulation of HIV-1 Gag was detected in the nucleoli of HeLa cells stably expressing the entire HIV-1 genome in a Rev-dependent fashion. These findings suggest that the RSV and HIV-1 Gag proteins undergo nucleolar trafficking in the setting of viral infection.

Directionality of nucleocytoplasmic transport of the retroviral gag protein depends on sequential binding of karyopherins and viral RNA.

Retroviral Gag polyproteins coopt host factors to traffic from cytosolic ribosomes to the plasma membrane, where virions are released. Before membrane transport, the multidomain Gag protein of Rous sarcoma virus (RSV) undergoes importin-mediated nuclear import and CRM1-dependent nuclear export, an intrinsic step in the assembly pathway. Transient nuclear trafficking of Gag is required for efficient viral RNA (vRNA) encapsidation, suggesting that Gag:vRNA binding might occur in the nucleus. Here, we show that Gag is imported into the nucleus through direct interactions of the Gag NC domain with importin-alpha (imp-alpha) and the MA domain with importin-11 (imp-11). The vRNA packaging signal, known as psi, inhibited imp-alpha binding to Gag, indicating that the NC domain does not bind to imp-alpha and vRNA simultaneously. Unexpectedly, vRNA binding also prevented the association of imp-11 with both the MA domain alone and with Gag, suggesting that the MA domain may bind to the vRNA genome. In contrast, direct binding of Gag to the nuclear export factor CRM1, via the CRM1-RanGTP heterodimer, was stimulated by psiRNA. These findings suggest a model whereby the genomic vRNA serves as a switch to regulate the ordered association of host import/export factors that mediate Gag nucleocytoplasmic trafficking for virion assembly. The Gag:vRNA interaction appears to serve multiple critical roles in assembly: specific selection of the vRNA genome for packaging, stimulating the formation of Gag dimers, and triggering export of viral ribonucleoprotein complexes from the nucleus.

Emotional responses of staff to assault in a pediatric state hospital.

In this study, we examined the emotional responses of staff to patient-on-staff assault at a state inpatient psychiatric hospital for children and adolescents. Staff (n = 93) completed self-report measures assessing general psychiatric functioning and symptoms of depression and anxiety. Staff assaulted by patients in the past six months (n = 59) were compared with those who had not been assaulted (n = 34). Direct-care staff were more likely to be assaulted than were other staff. Assaulted staff were more likely to report prior nonsexual assault by a stranger, higher anxiety, more somatic concerns, greater vulnerability and lack of control, and higher levels of impairment at work and were more likely to consider terminating employment than were non-assaulted staff. Our cross-sectional data suggest several differences in assaulted versus non-assaulted staff. Further studies are needed to determine whether differences in anxiety and traumatic events precede assaults or represent antecedent risk factors for being assaulted.

Importin-beta family members mediate alpharetrovirus gag nuclear entry via interactions with matrix and nucleocapsid.

The retroviral Gag polyprotein orchestrates the assembly and release of virus particles from infected cells. We previously reported that nuclear transport of the Rous sarcoma virus (RSV) Gag protein is intrinsic to the virus assembly pathway. To identify cis- and trans-acting factors governing nucleocytoplasmic trafficking, we developed novel vectors to express regions of Gag in Saccharomyces cerevisiae. The localization of Gag proteins was examined in the wild type and in mutant strains deficient in members of the importin-beta family. We confirmed the Crm1p dependence of the previously identified Gag p10 nuclear export signal. The known nuclear localization signal (NLS) in MA (matrix) was also functional in S. cerevisiae, and additionally we discovered a novel NLS within the NC (nucleocapsid) domain of Gag. MA utilizes Kap120p and Mtr10p import receptors while nuclear entry of NC involves the classical importin-alpha/beta (Kap60p/95p) pathway. NC also possesses nuclear targeting activity in avian cells and contains the primary signal for the import of the Gag polyprotein. Thus, the nucleocytoplasmic dynamics of RSV Gag depend upon the counterbalance of Crm1p-mediated export with two independent NLSs, each interacting with distinct nuclear import factors.

Detailed mapping of the nuclear export signal in the Rous sarcoma virus Gag protein.

The Rous sarcoma virus (RSV) Gag polyprotein undergoes transient nuclear trafficking as an intrinsic part of the virus assembly pathway. Nuclear export of Gag is crucial for the efficient production of viral particles and is accomplished through the action of a leptomycin B (LMB)-dependent nuclear export signal (NES) in the p10 domain (L. Z. Scheifele, R. A. Garbitt, J. D. Rhoads, and L. J. Parent, Proc. Natl. Acad. Sci. USA 99:3944-3949, 2002). We have now mapped the nuclear export activity to the C-terminal portion of the p10 sequence and identified the four hydrophobic amino acids within this region that comprise a leucine-rich NES. Alteration of these hydrophobic residues resulted in the accumulation of Gag proteins within the nucleus and a budding defect greater than that obtained with LMB treatment of cells expressing the wild-type Gag protein (Scheifele et al., Proc. Natl. Acad. Sci. USA 99:3944-3949, 2002). In addition, export of Gag from the nucleus was found to be a rate-limiting step in virus-like particle production. Consistent with a role for the NES sequence in viral replication, this cluster of hydrophobic residues in p10 is conserved across a wide range of avian retroviruses. Furthermore, naturally occurring substitutions within this region in related viruses maintained nuclear export activity and remained sensitive to the activity of LMB. Using gain-of-function approaches, we found that the hydrophobic motif in p10 was sufficient to promote the nuclear export of a heterologous protein and was positionally independent within the Gag polyprotein. Finally, the export pathway was further defined by the ability of specific nucleoporin inhibitors to prevent the egress of Gag from the nucleus, thereby identifying additional cellular mediators of RSV replication.

A review of mood disorders among juvenile offenders.

OBJECTIVES: This article provides an overview of what is known about the prevalence, diagnosis, and effective treatment of mood disorders among youths, particularly among juvenile offenders, and discusses the unique problems that arise for the delivery of treatment services. The relationship between mood disorders and disruptive or delinquent behaviors as well as the particular importance of proper diagnosis and treatment of mood disorders in this population are discussed. METHODS: A search was conducted of the MEDLINE and PsycINFO databases for articles that had been published since 1980 on mood disorders in the juvenile offender population as well as articles on adolescent mood disorders. RESULTS: The studies on the prevalence of mood disorders among juvenile offenders varied significantly in the methodology used and in the rates of prevalence found, although all studies showed that this population had high rates of mood disorders. The identification and effective treatment of mood disorders is critical because these disorders are a leading cause of suicide among adolescents and because mood disorders may contribute to or exacerbate delinquent and disruptive behaviors. CONCLUSIONS: Juvenile detainees have a constitutional right to needed mental health treatment. More comprehensive mental health services are required to ensure that juvenile offenders with mental illness are identified and cared for appropriately. Doing so not only will alleviate painful symptoms but may also contribute significantly to improvements in psychosocial functioning, interpersonal relations, and school performance and to decreases in delinquent, disruptive, and suicidal behaviors.

A prospective study of assault against staff by youths in a state psychiatric hospital.

OBJECTIVE: This study examined the frequency and nature of violence directed at staff in a state inpatient psychiatric hospital for children and adolescents. METHODS: A total of 215 assaults that occurred over a two-month period were examined by using information obtained from staff at the time of the assault and from the hospital database. Assaults were analyzed for situational characteristics of the incidents as well as the characteristics that best differentiated between assaultive and nonassaultive patients. RESULTS: Thirty-three percent of all hospitalized patients were involved in an assaultive incident. A majority of the patients who assaulted staff were neither involved in the juvenile justice system nor psychotic. Although youths who were involved in repeat assaults were more likely to be male, gender did not differentiate between those who were assaultive toward staff and those who were not. Some type of verbal direction or redirection (typically minor) on the part of the staff preceded a majority (68 percent) of the assaults. CONCLUSION: Preconceived notions about why youths assault staff at psychiatric hospitals do not appear to be validated by these data, which suggest a more complex picture.

Novel fungitoxicity assays for inhibition of germination-associated adhesion of Botrytis cinerea and Puccinia recondita spores.

Botrytis cinerea and Puccinia recondita spores adhere strongly to polystyrene microtiter plates coincident with germination. We developed assays for inhibition of spore adhesion in 96-well microtiter plates by using sulforhodamine B staining to quantify the adherent spores. In both organisms, fungicides that inhibited germination strongly inhibited spore adhesion, with 50% effective concentrations (EC(50)s) comparable to those for inhibition of germination. In contrast, fungicides that acted after germination in B. cinerea inhibited spore adhesion to microtiter plates only at concentrations much higher than their EC(50)s for inhibition of mycelial growth. Similarly, in P. recondita the ergosterol biosynthesis inhibitors myclobutanil and fenbuconazole acted after germination and did not inhibit spore adhesion. The assays provide a rapid, high-throughput alternative to traditional spore germination assays and may be applicable to other fungi.