Examining attitudes, beliefs and knowledge of effective practices in psychiatric rehabilitation in a hospital setting

OBJECTIVE: This brief report presents a staff training program based on psychiatric rehabilitation principles used in a hospital setting. The training program intervention significantly promoted the belief that mental illness does not necessarily limit functioning and also improved awareness of research findings, evidence-based practices and community services. METHODS: A randomized controlled study assessed the impact of the program on the staff's attitudes regarding psychiatric rehabilitation and recovery. RESULTS: Findings suggest that in-service training programs within a hospital setting can change staff attitudes in order to support psychiatric rehabilitation. CONCLUSIONS: A psychiatric rehabilitation forum, made up of representatives from all disciplines, including the medical directors of every ward, was set up in the hospital following the training program and has become the main avenue to disseminate information, messages, and goals to the staff at large and to the hospital administration. It is the forum that creates the shared vision about psychiatric rehabilitation within the hospital and has the task of facilitating implementation of services according to that vision.     

Plasma homocysteine level and functional outcome of patients with ischemic stroke

OBJECTIVE: To investigate the possible relationships between total plasma homocysteine level (tHcy) and functional outcome of stroke patients as evaluated by the FIM instrument. DESIGN: Retrospective chart analysis. SETTING: Inpatient stroke rehabilitation ward of a university-affiliated referral hospital. PARTICIPANTS: Consecutive patients (N=113) presenting with acute ischemic stroke. Patients were divided into 2 groups according to their tHcy levels (< or = 15 micromol/L, >15 micromol/L) and into 3 groups according to their FIM scores (low, < or =40; moderate, 41-80; high, >80). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The tHcy level was determined shortly after stroke onset by a high performance liquid chromatography method with fluorescence detection. Functional outcome was measured by the FIM instrument at admission and discharge. The tHcy level and FIM scores were obtained for all patients. Data outcomes were analyzed by t tests, 1-way analysis of variance, Mann-Whitney U, and Fisher exact tests, as well as by the 2 ordered polytomous logistic regression model. RESULTS: The 2 tHcy groups were similar in demographic, stroke, and comorbidity characteristics, differing only by higher frequency of hypertension in those with a tHcy greater than 15 micromol/L (51.7% vs 80.8%, respectively, P=.01). Compared with patients who had tHcy levels at 15 micromol/L or lower and were discharged from rehabilitation being in the highest FIM score group (>80), higher tHcy levels were not associated with a discharge FIM score of less than 40 (odds ratio [OR]=.77; 95% confidence interval [CI], 0.13-4.65; P=.77) or with a better functional outcome FIM score between 40 and 80 (OR=3.71; 95% CI, 0.73-18.99; P=.11). CONCLUSIONS: Our findings suggest that determination of tHcy level does not correlate with functional outcome in patients presenting for rehabilitation after acute ischemic stroke.     

Allelic 'choice' governs somatic hypermutation in vivo at the immunoglobulin kappa-chain locus

Monoallelic demethylation and rearrangement control allelic exclusion of the immunoglobulin kappa-chain locus (Igk locus) in B cells. Here, through the introduction of pre-rearranged Igk genes into their physiological position, the critical rearrangement step was bypassed, thereby generating mice producing B cells simultaneously expressing two different immunoglobulin-kappa light chains. Such 'double-expressing' B cells still underwent monoallelic demethylation at the Igk locus, and the demethylated allele was the 'preferred' substrate for somatic hypermutation in each cell. However, methylation itself did not directly inhibit the activation-induced cytidine-deaminase reaction in vitro. Thus, it seems that the epigenetic mechanisms that initially bring about monoallelic variable-(diversity)-joining rearrangement continue to be involved in the control of antibody diversity at later stages of B cell development.     

NZ51, a ring-expanded nucleoside analog,inhibits motility and viability of breast cancer cells by targeting the RNA helicase DDX3

DDX3X (DDX3), a human RNA helicase, is over expressed in multiple breast cancer cell lines and its expression levels are directly correlated to cellular aggressiveness. NZ51, a ring-expanded nucleoside analogue (REN) has been reported to inhibit the ATP dependent helicase activity of DDX3. Molecular modeling of NZ51 binding to DDX3 indicated that the 5:7-fused imidazodiazepine ring of NZ51 was incorporated into the ATP binding pocket of DDX3. In this study, we investigated the anticancer properties of NZ51 in MCF-7 and MDA-MB-231 breast cancer cell lines. NZ51 treatment decreased cellular motility and cell viability of MCF-7 and MDA-MB-231 cells with IC₅₀ values in the low micromolar range. Biological knockdown of DDX3 in MCF-7 and MDA-MB-231 cells resulted in decreased proliferation rates and reduced clonogenicity. In addition, NZ51 was effective in killing breast cancer cells under hypoxic conditions with the same potency as observed during normoxia. Mechanistic studies indicated that NZ51 did not cause DDX3 degradation, but greatly diminished its functionality. Moreover, in vivo experiments demonstrated that DDX3 knockdown by shRNA resulted in reduced tumor volume and metastasis without altering tumor vascular volume or permeability-surface area. In initial in vivo experiments, NZ51 treatment did not significantly reduce tumor volume. Further studies are needed to optimize drug formulation, dose and delivery. Continuing work will determine the in vitro-in vivo correlation of NZ51 activity and its utility in a clinical setting.     

Epigenetic ontogeny of the Igk locus during B cell development

To become accessible for rearrangement, the immunoglobulin kappa locus must undergo a series of epigenetic changes. This begins in pro-B cells with the relocation of both immunoglobulin kappa alleles from the periphery to the center of the nucleus. In pre-B cells, one allele became preferentially packaged into an active chromatin structure characterized by histone acetylation and methylation of histone H3 lysine 4, while the other allele was recruited to heterochromatin, where it was associated with heterochromatin protein-gamma and Ikaros. These events in cis made only one allele accessible to trans-acting factors, such as RelB, which mediated DNA demethylation, to facilitate rearrangement. These results suggest that early B lymphoid epigenetic changes generate differential structures that serve as the basis for allelic exclusion.     

Large-scale preparation of human anti-third-party veto cytotoxic T lymphocytes depleted of graft-versus-host reactivity: a new source for graft facilitating cells in bone marrow transplantation

Induction of donor type chimerism in mildly prepared hosts without graft-versus-host disease (GvHD) is a most desirable goal in bone morrow transplantation. We have recently demonstrated in a mouse model that donor veto cytotoxic T lymphocytes (CTLs) can facilitate the induction of donor type chimerism in sublethally irradiated recipients without causing GvHD if they are effectively depleted of alloreactivity against host cells by means of stimulation against a third party. We extend this approach to human cells, by preparing CTLs in two major steps: primary culture in the absence of interleukin 2, leading to death by neglect of antihost clones, and addition of interleukin 2 and subsequent dilution of antihost clones as a consequence of the expansion of the anti-third-party clones. CTLs prepared in this way specifically suppress host cytotoxic T cells directed against antigens of the donor, but not against fourth-party antigens, as demonstrated in a standard (51)Cr release assay. We conclude that human anti-third-party CTLs afford a new source of veto cells that are depleted of potential graft-versus-host-reactive clones. The cells generated by this approach could potentially be used to facilitate engraftment of allogeneic hematopoietic stem cells.