Needs among persons with human immunodeficiency virus and intellectual and developmental disabilities in community mental health care: a cross-sectional study.

BACKGROUND: The experience of having human immunodeficiency virus (HIV) is often associated with co-occurring mental health issues. Community mental health services are an important source of support for persons with HIV living in the community. Persons with intellectual disability (ID) are vulnerable to HIV and may have unique support needs beyond those without ID receiving community care. This study compared support needs of men with HIV in community mental health programmes, with and without ID. METHODS: The sample was composed of 138 HIV-positive men with and without ID receiving mental health case management from one community organisation in Ontario, Canada, on 31 March 2013. Staff-rated needs across 16 domains grouped into four clusters were measured using the Camberwell Assessment of Need: Basic needs (accommodation, food, public transportation, money and benefits); self-care/functional needs (looking after the home, self-care and daytime activities); health/safety needs (physical health, psychological distress, psychotic symptoms, safety to self and safety to others); and social needs (company, intimate relationships and sexual expression). Adjusted logistic regression models examined the association between ID and each need domain. RESULTS: One-quarter of the sample (n = 34/138, 24.6%) had co-occurring ID. Those with ID were more likely to have needs in the basic cluster [odds ratios: food 4.05 (1.14, 14.44), P:0.031; benefits 2.58 (1.05, 6.32), P:0.038)] and self-care/functional cluster [looking after the home (2.75 (1.17, 6.49), P:0.021); self-care (2.72 (1.18, 6.27), P:0.019)], but were less likely to have need for sexual expression: 0.35 (0.14,0.90), P:0.030) (social cluster). There were no differences in the domains in the health/safety cluster. CONCLUSION: Despite elevated cognitive needs in the basic and self-care/functional clusters for the ID group, limited other differences suggest that with moderate additional targeting, community mental health programmes for persons with HIV may be appropriate for men with ID.

A comparison of outpatients with intellectual disability receiving specialised and general services in Ontario's psychiatric hospitals.

BACKGROUND: This study compares outpatients with intellectual disability (ID) receiving specialised services to outpatients with ID receiving general services in Ontario's tertiary mental healthcare system in terms of demographics, symptom profile, strengths and resources, and clinical service needs. METHODS: A secondary analysis of Colorado Client Assessment Record data collected from all tertiary psychiatric hospitals in the province was completed for a stratified random sample of 246 outpatients identified as having ID, from both specialised and general programmes. RESULTS: Individuals with ID in specialised programmes differed from patients with ID in general programmes with regard to demographics, diagnostic profile, symptom presentation and recommended level of care. CONCLUSIONS: Further research is required to determine why individuals access some services over others and to evaluate whether specialised services are more appropriate for certain subgroups with ID than others.

Human cytomegalovirus inhibits major histocompatibility complex class II expression by disruption of the Jak/Stat pathway.

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that is able to persist for decades in its host. HCMV has evolved protean countermeasures for anti-HCMV cellular immunity that facilitate establishment of persistence. Recently it has been shown that HCMV inhibits interferon gamma (IFN-gamma)-stimulated MHC class II expression, but the mechanism for this effect is unknown. IFN-gamma signal transduction (Jak/Stat pathway) and class II transactivator (CIITA) are required components for IFN-gamma-stimulated MHC class II expression. In this study, we demonstrate that both a clinical isolate and a laboratory strain of HCMV inhibit inducible MHC class II expression at the cell surface and at RNA level in human endothelial cells and fibroblasts. Moreover, reverse transcriptase polymerase chain reaction and Northern blot analyses demonstrate that neither CIITA nor interferon regulatory factor 1 are upregulated in infected cells. Electrophoretic mobility shift assays reveal a defect in IFN-gamma signal transduction, which was shown by immunoprecipitation to be associated with a striking decrease in Janus kinase 1 (Jak1) levels. Proteasome inhibitor studies with carboxybenzyl-leucyl-leucyl-leucine vinyl sulfone suggest an HCMV-associated enhancement of Jak1 protein degradation. This is the first report of a mechanism for the HCMV-mediated disruption of inducible MHC class II expression and a direct virus-associated alteration in Janus kinase levels. These findings are yet another example of the diverse mechanisms by which HCMV avoids immunosurveillance and establishes persistence.

Fatal leukemia in interleukin 15 transgenic mice follows early expansions in natural killer and memory phenotype CD8+ T cells.

Inflammation likely has a role in the early genesis of certain malignancies. Interleukin (IL)-15, a proinflammatory cytokine and growth factor, is required for lymphocyte homeostasis. Intriguingly, the expression of IL-15 protein is tightly controlled by multiple posttranscriptional mechanisms. Here, we engineered a transgenic mouse to overexpress IL-15 by eliminating these posttranscriptional checkpoints. IL-15 transgenic mice have early expansions in natural killer (NK) and CD8+ T lymphocytes. Later, these mice develop fatal lymphocytic leukemia with a T-NK phenotype. These data provide novel evidence that leukemia, like certain other cancers, can arise as the result of chronic stimulation by a proinflammatory cytokine.

A BAC-based physical map of the major autosomes of Drosophila melanogaster.

We constructed a bacterial artificial chromosome (BAC)-based physical map of chromosomes 2 and 3 of Drosophila melanogaster, which constitute 81% of the genome. Sequence tagged site (STS) content, restriction fingerprinting, and polytene chromosome in situ hybridization approaches were integrated to produce a map spanning the euchromatin. Three of five remaining gaps are in repeat-rich regions near the centromeres. A tiling path of clones spanning this map and STS maps of chromosomes X and 4 was sequenced to low coverage; the maps and tiling path sequence were used to support and verify the whole-genome sequence assembly, and tiling path BACs were used as templates in sequence finishing.

Large-scale purification of human BACE expressed in mammalian cells and removal of the prosegment with HIV-1 protease to improve crystal diffraction.

BACE, or beta-secretase, is an attractive target in the treatment of Alzheimer's Disease because of its involvement in the generation of amyloid beta peptides. BACE is a type I transmembrane aspartyl protease composed of pre-, pro-, catalytic, transmembrane and cytoplasmic domains. For the present study, the coding sequence was truncated just before the transmembrane domain and the resulting construct was extended with the C-terminal addition of a (His)(6) and expressed in several mammalian host cells. The enzyme expressed in CHO cells had the best crystallographic behavior and was purified in large quantities in a three step procedure. The purified BACE was comprised of two forms, namely the full length proBACE construct beginning with Thr(1), and a derivative missing the first 24 amino acids beginning with E(25). These BACE precursors co-crystallized in the presence of inhibitors yielding structures to 3.2 A resolution. HIV-1 protease treatment of this mixture resulted in complete cleavage of the F(39)-V(40) bond, leaving the V(40)EM...ES(432) (His)(6) derivative that was purified yielding an enzyme that was no more active than untreated BACE but co-crystallized with inhibitors producing well shaped, bipyramidal co-crystals diffracting to 2.6 A resolution.

A comparison of patients with intellectual disability receiving specialised and general services in Ontario's psychiatric hospitals.

BACKGROUND: Over the years, the closure of institutions has meant that individuals with intellectual disabilities (IDs) must access mainstream (i.e. general) mental health services. However, concern that general services may not adequately meet the needs of patients with ID and mental illness has led to the development and implementation of more specialised programmes. This study compares patients with ID receiving specialised services to patients with ID receiving general services in Ontario's tertiary mental healthcare system in terms of demographics, symptom profile, strengths and resources and clinical service needs. METHOD: A secondary analysis of Colorado Client Assessment Record data collected from all tertiary psychiatric hospitals in the province was completed for all 371 inpatients with ID, from both specialised and general programmes. RESULTS: Inpatients in specialised programmes were more likely to have a diagnosis of mood disorder and were less likely to have a substance abuse or psychotic disorder. Individuals receiving specialised services had higher ratings of challenging behaviour than those in more general programmes. The two groups did not differ significantly in terms of recommended level of care, although more inpatients from specialised programmes were rated as requiring Level 4 care than inpatients from general programmes. CONCLUSIONS: In Ontario, inpatients in specialised and general programmes have similar overall levels of need but unique clinical profiles that should be taken into consideration when designing interventions for them.

ISGF3 gamma p48, a specificity switch for interferon activated transcription factors.

Interferon (IFN) induces gene expression by phosphorylating latent transcription factors of the STAT family. Two different STAT multimeric complexes that bind distinct enhancer elements are activated by IFN alpha and IFN gamma, dictated by the DNA-binding protein ISGF3 gamma p48. This protein, a member of the IFN regulatory factor (IFR) family, acts as an adaptor protein to redirect STAT multimers from their intrinsic palindromic sequence specificity to interactions with a composite element composed of an IRF site juxtaposed with a STAT half-site. Sequence similarity within the IRF family suggests that other members could serve as adaptor proteins for transcriptional activators. Recent evidence suggests that PIP (LSIRF) sequesters the Ets protein PU.1 at a composite DNA element lends support to this adaptor hypothesis.

Identification of cDNAs corresponding to mosquito ribosomal protein genes.

Sequences encoding mosquito (Aedes albopictus) ribosomal proteins L8, L14 and L31 were identified from a cDNA library made from size-selected polyadenylated mRNA. Candidate cDNAs corresponding to moderately abundant mRNAs were screened by translation of hybrid-selected transcripts in wheat-germ lysates. Translation products were extracted with acetic acid and analyzed by electrophoresis in two dimensions in the presence of unlabeled ribosomal proteins. The identity of translation products that coelectrophoresed with purified ribosomal protein standards was supported by peptide mapping. The cDNAs corresponding to L8 (pL8) and L31 (pL31) hybridized to cytoplasmic mRNAs of 1.4 and 0.9 kb, respectively. In Southern blots of genomic DNA digested with BamHI, HindIII or EcoRI, the cDNA inserts from both pL8 and pL31 gave simple hybridization patterns suggestive of a low copy number for mosquito ribosomal protein genes.

Transient expression of the chloramphenicol acetyltransferase gene in cultured mosquito cells.

A recombinant plasmid in which the bacterial chloramphenicol acetyltransferase (CAT) gene is under the control of the Drosophila heat-shock protein (hsp) 70 promoter has been introduced into cultured mosquito (Aedes albopictus) cells using 1,5-dimethyl-1,5-diazaundecamethylene polymethobromide (polybrene) and dimethylsulfoxide (DMSO). CAT activity was induced by incubating transfected cells at 37 degrees C, and high levels of enzyme activity were maintained for more than 24 h after the temperature shock. Transfected DNA was maintained in the cells for at least 4 days. These experiments document an effective method for introducing purified DNA into cultured mosquito cells.

Criminality and mental illness: a study of arrest rates in a rural state.

The authors examined cumulative arrests for the period of 1964-1973 for psychiatric patients admitted to a state hospital in 1969 (286 men and 175 women) and for the general population in Wyoming. Male patients were arrested as often as or more often than individuals in the general population. No men diagnosed as schizophrenic were arrested for crimes against persons; one-fourth of arrests among individuals diagnosed as alcoholics were for such crimes. Arrest rates among women patients seemed to parallel those of women in the general population, although the sample was too small for definite conclusions. Male patients were arrested significantly less often following dischanrge than before hospitalization.

A quantitative analysis of rat adrenal chromaffin tissue: morphometric analysis at tissue and cellular level correlated with catecholamine content.

A morphometric analysis of normal Wistar rat adrenal medulla following perfusion fixation and Araldite embedding, was correlated with catecholamine levels on fresh tissue, measured by high-performance liquid chromatography. The mean volume of whole adrenal is 13.2 mm3 and the mean medullary volume 1.3 mm3. Volume density estimates showed that the medulla is composed of 63% chromaffin tissue with an adrenaline to noradrenaline storing cell ratio of 4.4:1. The vasculature occupies 20%, neuronal tissue 5% and interstitial tissues 12% of the medulla. A comparison was made of cell volumes, cell numbers and volume and surface density estimates of cytoplasmic organelles in adrenaline and noradrenaline storing cells. The mean cell volume of adrenaline storing cells at 1300 micron3 is larger than that of noradrenaline storing cells at 980 micron3. A single adrenal medulla contains 4.4-5.7 X 10(5) adrenaline cells and 1.5-1.9 X 10(5) noradrenaline cells. Chromaffin granules account for approximately 30% of the volume of the cytoplasm; the numerical density of granules at different sites in the cell was calculated for adrenaline cells. The volume density of mitochondria (4%) and the surface density of mitochondrial membranes (the ratio of outer to inner membrane being approximately 1:2.3) were similar in both cell types. Rough endoplasmic reticulum was the only organelle to show a significant difference in volume and surface density between the two cell types. Adrenaline storing cells have stacks of rough endoplasmic reticulum which have two to three times the surface and volume densities of that found diffusely scattered throughout noradrenaline cells. The adrenaline content of an adrenaline storing cell is 0.14 X 10(-6) microM and that of a granule 3.0 X 10(-12) or 3.8 X 10(-12) mumoles depending on the method of calculation. The noradrenaline content of noradrenaline storing cells can only be calculated on the assumption that all noradrenaline is stored in this cell type though it is likely that some is contained within adrenaline cells. Based on this assumption the noradrenaline content is 0.17 X 10(-6) mumoles per cell and 5 X 10(-12) mumoles per granule. The present study provides baseline morphometric data on the rat adrenal medulla at tissue and cellular level correlated with amine levels in adrenaline and noradrenaline storing cells and granules.

PKR protection against intranasal vesicular stomatitis virus infection is mouse strain dependent.

The interferon-induced antiviral state is mediated by interferon-stimulated genes that are upregulated in concert after stimulation by type I interferons. Because so many viruses encode strategies to inactivate the interferon-inducible double-stranded RNA (dsRNA)-dependent protein kinase PKR, this protein is likely to be a major player in antiviral defense. Here we demonstrate the increased susceptibility of PKR-/- animals to vesicular stomatitis virus (VSV) by the intranasal route, but also demonstrate that the protective effects of PKR are mouse strain dependent. We have found the difference between wild-type-BALB/c and 129SvEv animals to be on the order of 5 logs, with high levels of virus present in the lungs of BALB/c but not 129SvEv animals. To evaluate the sensitivity of PKR-/- mice to VSV clearly, the PKR mutation was bred onto the resistant 129SvEv background. The increased sensitivity of PKR-/- mice, compared to PKR+/+ strain-matched controls, is on the order of 10-fold as measured by median lethal dose (LD50). PKR-/- 129 mice support VSV replication in the lung unlike controls. While this result clearly demonstrates an important role for PKR in protection against VSV infection of the lung, it also underlines the importance of other host factors in containing a viral infection.

Borderline personality disorder and substance use disorders: a review and integration.

The empirical literature on the comorbidity between borderline personality disorder (BPD) and substance use disorders (SUDs) is reviewed. BPD-SUD comorbidity data obtained from studies published from 1987 to 1997 document the frequent co-occurrence of these diagnoses. Methodological issues and theoretical models for understanding this co-occurrence are discussed. Finally, we present our conceptualization of the relations and interactions of the major factors influencing the development of BPD and contributing to the comorbidity between BPD and SUDs.

Needs-based planning: evaluation of a level-of-care planning model.

With the closure of a number of provincial psychiatric hospitals planned, the Ministry of Health of Ontario has commissioned a series of planning projects to identify alternative placements for current hospital patients. The goal is to match need to care in the least restrictive setting. A systematic, clinically driven planning process was implemented that involved three steps: development of a continuum of levels of care representing increasingly intensive and more restrictive supports, development of criteria and decision rules for placement, and comprehensive needs assessment of current patients using the Colorado Client Assessment Record. Results showed that only 10% of current inpatients need to remain in the hospital, and over 60% could live independently in the community with appropriate supports. Evidence supports concurrent validity of the planning model, but further work is needed to assess whether recommended levels of care effectively meet consumer needs in the least restrictive setting.

Phenylpiperazine derivatives with selectivity for dopamine D3 receptors modulate cocaine self-administration in rats.

This study examined cocaine self-administration after pretreatments with three structurally related compounds that bind selectively to dopamine D3 receptors (D3Rs) relative to the D2 receptor subtype (D2Rs) and exhibit varying intrinsic activities in the forskolin-stimulated adenylyl cyclase assay. The compounds are: a) WC10, a D3R weak partial agonist/antagonist with 42-fold D3R:D2R selectivity, b) WC26, a 51-fold selective D3R partial agonist, c) WC44, a 23-fold selective D3R agonist. Rats were stabilized on a multiple variable-interval 60-s (VI60) schedule with alternating components of sucrose (45 mg pellets) or cocaine reinforcement (0.375 mg/kg, IV) and then tested for effects of the WC compounds (0.0, 1.0, 3.0, 5.6, or 10.0 mg/kg, IP). Another cohort was trained to self-administer cocaine (0.75 mg/kg, IV) on a VI60 schedule then tested with various doses of cocaine available (0.0-1.5 mg/kg, IV) following pretreatment with WC10 (5.6 or 10.0 mg/kg) or WC44 (10.0 mg/kg). WC10 and WC26 decreased both cocaine and sucrose reinforcement rates at the 10.0 mg/kg dose, whereas WC44 decreased only cocaine reinforcement rate at this dose. Furthermore, WC26 and WC44 increased response latency for cocaine but not sucrose. In the cocaine dose-response experiment, WC10 and WC44 flattened the dose-effect function of cocaine reinforcement rate. All compounds decreased spontaneous locomotion. WC10 and WC26 also reduced cocaine-induced locomotion. These results support the targeting of D3Rs for treatments for cocaine dependence. WC26 and WC44, in particular, show promise as they increased the latency to respond for cocaine but not sucrose, suggesting selective reduction of the motivation for cocaine.

Housing homeless women: a consumer preference study.

Consumer preference surveys can provide valuable information on which to base the planning and development of housing for groups with special needs. The authors describe a survey that explored the housing histories, problems, needs, and preferences of a sample of 38 chronically homeless women contacted in metropolitan Toronto hostels and drop-in centers. Despite having multiple mental and physical health problems, the women showed a strong preference for a normal, independent living situation. However, they acknowledged the need for a range of supportive services to maintain themselves in such a situation. The women strongly opposed being housed in settings with mentally ill persons, with alcohol or drug abusers, and with those involved in criminal activities.

Pre- and posthospitalization alcoholic arrests in a rural state.

Arrest rates of 180 male alcoholics admitted to the Wyoming State Hospital in 1969 were compared with the general Wyoming population during 1965--1973. Results indicated: (1) 67% of the alcoholics had no arrests before or after hospitalization; (2) prehospitalization arrest rates of alcoholics were higher than the general population for robbery, assault, sex offenses, theft, public intoxication, drunk driving, traffic offenses, and vagrancy; (3) following hospitalization, alcoholic arrest rates were reduced significantly in all categories except robbery and embezzlement and fraud; and (4) posthospitalization alcoholic arrest rates were lower than the general population for all offenses except robbery, public intoxication, and DWI.

Control of Sindbis virus infection by antibody in interferon-deficient mice.

Antibodies clear Sindbis virus from infected animals through an unknown mechanism. To determine whether interferon-induced pathways are required for this clearance, we examined mice which are unable to respond to alpha/beta interferon or gamma interferon. Although extremely susceptible to infection, such mice survived and completely cleared virus if antibodies against Sindbis virus were given.