Planning the restructuring of long-term care: The demand,need and provision of institutional long-term care beds in Newfoundland and Labrador

The Canadian population is aging. In Newfoundland and Labrador, nursing homes and supervised care facilities provide Long-Term Care (LTC). There may be a mismatch between the provision of LTC beds and clients' needs. To compare the type and annual rate of clients seeking placement, to LTC, incident annual cohorts (N = 1,496) in five provincial health regions within Newfoundland and Labrador were compared using objective measures of disability. Client need was assessed using a decision tree and the optimal distribution of LTC beds was determined.     

Case-control study of lymphoid neoplasm in three French areas: description, alcohol and tobacco consumption.

A multi-centre hospital-based case-control study was conducted in three regions of France between 2000 and 2003 in order to establish the risk factors of lymphoid neoplasms. We report here results concerning alcohol and tobacco consumption. A total of 298 cases and 276 controls, case-matched by inclusion centre, age and sex were included. Cases were classified according to the World Health Organization classification and validated by an expert panel of eight pathologists. Overall alcohol intake did not incur any risk increase for non-Hodgkin's lymphoma. Wine consumption marginally increased the risk of follicular lymphoma [odds ratio=2.19 (0.83-5.80)], with a higher risk for drinkers who started before the age of 20 years [odds ratio=4.04 (1.19-13.76)] and for drinkers who consumed more than 19 g of alcohol per day [odds ratio=4.37 (1.04-18.45)]. Beer and spirit consumption was not linked to non-Hodgkin's lymphoma risk. Tobacco consumption did not show a risk increase. The risk increase of follicular lymphoma due to wine consumption was new. We discuss this risk based on the French context, France being the European country with the highest alcohol consumption, particularly of wine.     

Three-dimensional mapping of hippocampal anatomy in unmedicated and lithium-treated patients with bipolar disorder.

Declarative memory impairments are common in patients with bipolar illness, suggesting underlying hippocampal pathology. However, hippocampal volume deficits are rarely observed in bipolar disorder. Here we used surface-based anatomic mapping to examine hippocampal anatomy in bipolar patients treated with lithium relative to matched control subjects and unmedicated patients with bipolar disorder. High-resolution brain magnetic resonance images were acquired from 33 patients with bipolar disorder (21 treated with lithium and 12 unmedicated), and 62 demographically matched healthy control subjects. Three-dimensional parametric mesh models were created from manual tracings of the hippocampal formation. Total hippocampal volume was significantly larger in lithium-treated bipolar patients compared with healthy controls (by 10.3%; p=0.001) and unmedicated bipolar patients (by 13.9%; p=0.003). Statistical mapping results, confirmed by permutation testing, revealed localized deficits in the right hippocampus, in regions corresponding primarily to cornu ammonis 1 subfields, in unmedicated bipolar patients, as compared to both normal controls (p=0.01), and in lithium-treated bipolar patients (p=0.03). These findings demonstrate the sensitivity of these anatomic mapping methods for detecting subtle alterations in hippocampal structure in bipolar disorder. The observed reduction in subregions of the hippocampus in unmedicated bipolar patients suggests a possible neural correlate for memory deficits frequently reported in this illness. Moreover, increased hippocampal volume in lithium-treated bipolar patients may reflect postulated neurotrophic effects of this agent, a possibility warranting further study in longitudinal investigations.     

The Relation between Work-related Psychosocial Factors and the Development of Depression

This review is based on a literature search made in January2007 on request by the Danish National Board of Industrial Injuries.The search in PubMed, EMBASE, and PsycINFO resulted in morethan 1,000 publications. This was reduced to 14 after the titles,abstracts, and papers were evaluated by using the followingcriteria: 1) a longitudinal study, 2) exposure to work-relatedpsychosocial factors, 3) the outcome a measure of depression,4) relevant statistical estimates, and 5) nonduplicated publication.Of the 14 studies, seven used standardized diagnostic instrumentsas measures of depression, whereas the other seven studies usedself-administered questionnaires. The authors found moderateevidence for a relation between the psychological demands ofthe job and the development of depression, with relative risksof approximately 2.0. However, indication of publication biasweakens the evidence. Social support at work was associatedwith a decrease in risk for future depression, as all four studiesdealing with this exposure showed associations with relativerisks of about 0.6. Even if this literature study has identifiedwork-related psychosocial factors that in high-quality epidemiologicstudies predict depression, studies are still needed that assessin more detail the duration and intensity of exposure necessaryfor developing depression. depression • prospective studies • psychology • work     

Ethanol potentiates dopamine uptake and increases cell surface distribution of dopamine transporters expressed in SK-N-SH and HEK-293 cells.

Ethanol increases dopaminergic release in the reward and reinforcement areas of the brain. The primary protein responsible for terminating dopamine (DA) neurotransmission is the plasma membrane-bound dopamine transporter (DAT). In vitro electrophysiological and biochemical studies in Xenopus laevis oocytes have previously shown ethanol potentiates DAT function and increases transporter-binding sites. The potentiating effect of ethanol on the transporter is eliminated in Xenopus oocytes by the DAT mutation glycine 130 to threonine. However, ethanol's action on DAT functional regulation has yet to be examined in mammalian cell expression systems. To further understand the molecular mechanisms of ethanol's action on DAT, we determined the direct mechanistic action of short-term (相似文献   

Efficient recovery of fluoroquinolone-susceptible and fluoroquinolone-resistant Escherichia coli strains from frozen samples.

We assessed the rate of recovery of fluoroquinolone-resistant and fluoroquinolone-susceptible Escherichia coli isolates from culture of frozen perirectal swab samples compared with the results for culture of the same specimen before freezing. Recovery rates for these 2 classes of E. coli were 91% and 83%, respectively. The majority of distinct strains recovered from the initial sample were also recovered from the frozen sample. The strains that were not recovered were typically present only in low numbers in the initial sample. These findings emphasize the utility of frozen surveillance samples.     

Evaluation of beneficial and adverse effects of glucocorticoids on a newly developed full-thickness skin model.

Glucocorticoids (GCs) are highly effective compounds widely used in the treatment of inflammatory diseases; however, they offer distinct adverse effects such as skin thinning in response to long-term topical treatment. Nevertheless it is difficult to deduce the safety of a newly synthesized compound from its structural formula. Efficient assay systems that measure beneficial and adverse effects are needed. In the present study the applicability of a three-dimensional full-thickness skin model (FTSM) is tested to display GC-induced effects regarding anti-inflammation and atrophy. It is shown that topical application of a commercial GC ointment suppresses the ultraviolet (UV)B induced induction of interleukin (IL)-6 and IL-8. Addition of purified betamethasone-17-valerate, prednicarbate and clobetasol-17-propionate to the culture medium for 14 days caused a reduction in the number of epidermal cell-layers corresponding to the atrophic risk found in vivo. Similarly, repeated topical application of five GC creams induced epidermal thinning. Evidence is given that the inhibitory effect on keratinocyte proliferation contributes to this effect. Furthermore, dermal thinning was monitored by measuring type I collagen synthesis; a decreased collagen synthesis similar to the in vivo situation is shown. The present study demonstrates the versatility of this FTSM in the validation of effectiveness and safety of GCs.     

EXEL-7647 inhibits mutant forms of ErbB2 associated with lapatinib resistance and neoplastic transformation.

PURPOSE: Mutations associated with resistance to kinase inhibition are an important mechanism of intrinsic or acquired loss of clinical efficacy for kinase-targeted therapeutics. We report the prospective discovery of ErbB2 mutations that confer resistance to the small-molecule inhibitor lapatinib. EXPERIMENTAL DESIGN: We did in vitro screening using a randomly mutagenized ErbB2 expression library in Ba/F3 cells, which were dependent on ErbB2 activity for survival and growth. RESULTS: Lapatinib resistance screens identified mutations at 16 different ErbB2 amino acid residues, with 12 mutated amino acids mapping to the kinase domain. Mutations conferring the greatest lapatinib resistance cluster in the NH2-terminal kinase lobe and hinge region. Structural computer modeling studies suggest that lapatinib resistance is caused by multiple mechanisms; including direct steric interference and restriction of conformational flexibility (the inactive state required for lapatinib binding is energetically unfavorable). ErbB2 T798I imparts the strongest lapatinib resistance effect and is analogous to the epidermal growth factor receptor T790M, ABL T315I, and cKIT T670I gatekeeper mutations that are associated with clinical drug resistance. ErbB2 mutants associated with lapatinib resistance transformed NIH-3T3 cells, including L755S and T733I mutations known to occur in human breast and gastric carcinomas, supporting a direct mechanism for lapatinib resistance in ErbB2-driven human cancers. The epidermal growth factor receptor/ErbB2/vascular endothelial growth factor receptor inhibitor EXEL-7647 was found to inhibit almost all lapatinib resistance-associated mutations. Furthermore, no ErbB2 mutations were found to be associated with EXEL-7647 resistance and lapatinib sensitivity. CONCLUSIONS: Taken together, these data suggest potential target-based mechanisms of resistance to lapatinib and suggest that EXEL-7647 may be able to circumvent these effects.