Pramipexole effects on startle gating in rats and normal men

Dopamine D3 receptors regulate sensorimotor gating in rats, as evidenced by changes in prepulse inhibition (PPI) of startle after acute administration of D3 agonists and antagonists. In this study, we tested the effects of the D3-preferential agonist, pramipexole, on PPI in normal men and Sprague–Dawley rats. Acoustic startle and PPI were tested in clinically normal men, comparing the effects of placebo vs. 0.125 mg (n = 20) or placebo vs. 0.1875 mg (n = 20) pramipexole, in double blind, crossover designs. These measures were also tested in male Sprague–Dawley rats using a parallel design [vehicle vs. 0.1 mg/kg (n = 8), vehicle vs. 0.3 mg/kg (n = 8) or vehicle vs. 1.0 mg/kg pramipexole (n = 8)]. Autonomic and subjective measures of pramipexole effects and several personality instruments were also measured in humans. Pramipexole increased drowsiness and significantly increased PPI at 120-ms intervals in humans; the latter effect was not moderated by baseline PPI or personality scale scores. In rats, pramipexole causes a dose-dependent reduction in long-interval (120 ms) PPI, while low doses actually increased short-interval (10–20 ms) PPI. Effects of pramipexole on PPI in rats were independent of baseline PPI and changes in startle magnitude. The preferential D3 agonist pramipexole modifies PPI in humans and rats. Unlike indirect DA agonists and mixed D2/D3 agonists, pramipexole increases long-interval PPI in humans, in a manner that is independent of baseline PPI and personality measures. These findings are consistent with preclinical evidence for differences in the D2- and D3-mediated regulation of sensorimotor gating

State Transition Graphs for Semantic Analysis of Movement Behaviours

A behaviour can be defined as a sequence of states or activities occurring one after another. A behaviour consisting of a finite number of reoccurring states/activities may be represented by a directed weighted graph with nodes and edges corresponding, respectively, to the possible states and transitions between them, while the weights represent the probabilities or frequencies of the state and transition occurrences. The same applies to multiple behaviours sharing the same set of possible states. In analysis of movement data, state transition graphs can be used to represent semantic abstractions of mobility behaviours, where states correspond to semantic categories of visited places (such as ‘home’, ‘work’, ‘shop’), activities of moving objects (‘driving’, ‘walking’, ‘exercising’, etc.) or characteristics of the movement (‘straight movement’, ‘sharp turn’, ‘acceleration’, ‘stop’, etc.). Such a representation supports the exploration and analysis of the semantic aspect (i.e. the meaning or purposes) of movement. For comprehensive analysis of movement data, state transition graphs need to be combined with representations reflecting the spatial and temporal aspects of the movement. This requires appropriate coordination between different visual displays (graphs, maps and temporal views) and appropriate reaction to analytical operations applied to any of the representations of the same data. We define in an abstract way the reactions of a graph display to analytical operations of querying, partitioning and direct selection. We also propose visual and interactive display features supporting comparisons between data subsets and between results of different operations. We demonstrate the use of the display features by examples of real-world and synthetic data sets

Invasive carcinomas of the male breast: a morphologic study of the distribution of histologic subtypes and metastatic patterns in 778 cases

The current investigation was conducted to evaluate the proportional distribution of the various histologic subtypes (including newly recognized variants) of male breast carcinomas, to determine whether any histologic subtypes occur with a frequency that is markedly discordant with the expected frequencies from published data on parallel female breast tumors. We also aimed to document the distribution of malignancies metastatic to the breast. Seven hundred fifty-nine archived cases of primary invasive carcinoma involving the male breast were retrieved and subcategorized into histologic subtypes according to contemporary criteria. Six hundred forty-three (84.7%) tumors were pure infiltrating ductal carcinoma (IDC) not otherwise specified. The most common of the remainder included papillary carcinoma with invasion in the form of IDC (n = 34), mixed IDC and mucinous carcinoma (n = 26), and pure mucinous carcinoma (n = 21). In 19 cases, metastases from other sites involved the breast, most commonly (58%) cutaneous melanoma. Invasive carcinoma of the male breast appears to display a morphologic spectrum and distribution of histologic subtypes that is comparable to those of the female breast, with some expected variation. Compared with published experience on their female counterparts, there is a two-fold increase in the frequency of invasive papillary carcinoma in the male breast. Finally, the most common tumor metastatic to the male breast in this series was cutaneous melanoma

Time to positivity in blood cultures of adults with Streptococcus pneumoniae bacteremia

BACKGROUND: previous studies have established that bacterial blood concentration is related with clinical outcome. Time to positivity of blood cultures (TTP) has relationship with bacterial blood concentration and could be related with prognosis. As there is scarce information about the usefulness of TTP, we study the relationship of TTP with clinical parameters in patients with Streptococcus pneumoniae bacteremia. METHODS: TTP of all cases of Streptococcus pneumoniae bacteremia, detected between January 1995 and December 2004 using the BacT/Alert automated blood culture system in a teaching community hospital was analyzed. When multiple cultures were positive only the shortest TTP was selected for the analysis. RESULTS: in the study period 105 patients with Streptococcus pneumoniae bacteremia were detected. Median TTP was 14.1 hours (range 1.2 h to 127 h). Immunosuppressed patients (n = 5), patients with confusion (n = 19), severe sepsis or shock at the time of blood culture extraction (n = 12), those with a diagnosis of meningitis (n = 7) and those admitted to the ICU (n = 14) had lower TTP. Patients with TTP in the first quartile were more frequently hospitalized, admitted to the ICU, had meningitis, a non-pneumonic origin of the bacteremia, and a higher number of positive blood cultures than patients with TTP in the fourth quartile. None of the patients with TTP in the 90(th )decile had any of these factors associated with shorter TTP, and eight out of ten patients with TTP in the 10(th )decile had at least one of these factors. The number of positive blood cultures had an inverse correlation with TTP, suggesting a relationship of TTP with bacterial blood concentration. CONCLUSION: Our data support the relationship of TTP with several clinical parameters in patients with Streptococcus pneumoniae bacteremia, and its potential usefulness as a surrogate marker of outcome

The DISC (Diabetes in Social Context) Study-evaluation of a culturally sensitive social network intervention for diabetic patients in lower socioeconomic groups: a study protocol

<p>Abstract</p> <p>Background</p> <p>Compared to those in higher socioeconomic groups, diabetic patients in lower socioeconomic groups have less favourable metabolic control and experience more diabetes-related complications. They encounter specific barriers that hinder optimal diabetes self-management, including a lack of social support and other psychosocial mechanisms in their immediate social environments. <it>Powerful Together with Diabetes </it>is a culturally sensitive social network intervention specifically targeted to ethnic Dutch, Moroccan, Turkish, and Surinamese diabetic patients in lower socioeconomic groups. For ten months, patients will participate in peer support groups in which they will share experiences, support each other in maintaining healthy lifestyles, and learn skills to resist social pressure. At the same time, their significant others will also receive an intervention, aimed at maximizing support for and minimizing the negative social influences on diabetes self-management. This study aims to test the effectiveness of <it>Powerful Together with Diabetes</it>.</p> <p>Methods/Design</p> <p>We will use a quasi-experimental design with an intervention group (Group 1) and two comparison groups (Groups 2 and 3), N = 128 in each group. Group 1 will receive <it>Powerful Together with Diabetes</it>. Group 2 will receive <it>Know your Sugar</it>, a six-week group intervention that does not focus on the participants' social environments. Group 3 receives standard care only. Participants in Groups 1 and 2 will be interviewed and physically examined at baseline, 3, 10, and 16 months. We will compare their haemoglobin A1C levels with the haemoglobin A1C levels of Group 3. Main outcome measures are haemoglobin A1C, diabetes-related quality of life, diabetes self-management, health-related, and intermediate outcome measures. We will conduct a process evaluation and a qualitative study to gain more insights into the intervention fidelity, feasibility, and changes in the psychosocial mechanism in the participants' immediate social environments.</p> <p>Discussion</p> <p>With this study, we will assess the feasibility and effectiveness of a culturally sensitive social network intervention for lower socioeconomic groups. Furthermore, we will study how to enable these patients to optimally manage their diabetes. This trial is registered in the Dutch Trial Register: NTR1886</p

Nipah Virus Infects Specific Subsets of Porcine Peripheral Blood Mononuclear Cells

Nipah virus (NiV), a zoonotic paramyxovirus, is highly contagious in swine, and can cause fatal infections in humans following transmission from the swine host. The main viral targets in both species are the respiratory and central nervous systems, with viremia implicated as a mode of dissemination of NiV throughout the host. The presented work focused on the role of peripheral blood mononuclear cells (PBMC) in the viremic spread of the virus in the swine host. B lymphocytes, CD4−CD8−, as well as CD4+CD8− T lymphocytes were not permissive to NiV, and expansion of the CD4+CD8− cells early post infection was consistent with functional humoral response to NiV infection observed in swine. In contrast, significant drop in the CD4+CD8− T cell frequency was observed in piglets which succumbed to the experimental infection, supporting the hypothesis that antibody development is the critical component of the protective immune response. Productive viral replication was detected in monocytes, CD6+CD8+ T lymphocytes and NK cells by recovery of infectious virus in the cell supernatants. Virus replication was supported by detection of the structural N and the non-structural C proteins or by detection of genomic RNA increase in the infected cells. Infection of T cells carrying CD6 marker, a strong ligand for the activated leukocyte cell adhesion molecule ALCAM (CD166) highly expressed on the microvascular endothelial cell of the blood-air and the blood-brain barrier may explain NiV preferential tropism for small blood vessels of the lung and brain

Identification of mRNAs differentially-expressed between benign and malignant breast tumour cells

Two suppression subtracted cDNA libraries have been constructed, one containing cDNAs to mRNAs present at a higher level in a benign human breast tumour-derived cell line relative to the malignant mammary cell line, MCF-7, and the other containing cDNAs present at a higher level in the MCF-7 cells relative to the benign cells. Randomly-picked cloned DNAs have been sequenced yielding 29 and 128 different cDNAs from the benign and malignant libraries, respectively. Using reverse Northern hybridisation, 76% and 83% of the cDNAs were differentially expressed by greater than two-fold, whilst 14% and 11% of cDNAs in the respective libraries were differentially expressed by more than 15-fold. Amongst these were oestrogen-responsive cDNAs and expressed sequence tags. One such oestrogen-responsive expressed sequence tag, M41, is transcribed from a gene located on chromosome 21q22.3, within an intron of a larger gene. The M41 gene contains oestrogen response elements, one of which is associated with alu repeats. M41 mRNA is expressed at a statistically significantly higher level in human breast cancer specimens than in normal human breast and benign lesions. In carcinomas, its up-regulation is associated with the development of the malignant cell

Report of depressive symptoms on waiting list and mortality after liver and kidney transplantation: a prospective cohort study

International audienceABSTRACT: BACKGROUND: Little research has explored pre-transplantation psychological factors as predictors of outcome after liver or kidney transplantation. Our objective is to determine whether report of depressive symptoms on waiting list predicts outcome of liver and kidney transplantation. METHODS: Patients on waiting list for liver or kidney transplantation were classified for report or non-report of depressive symptoms on waiting list. 339 were transplanted 6 months later on average, and followed prospectively. The main outcome measures were graft failure and mortality 18 months post-transplantation. RESULTS: Among the 339 patients, 51.6% reported depressive symptoms on waiting list, 16.5% had a graft failure and 7.4% died post-transplantation. Report of depressive symptoms on waiting list predicted a 3 to 4-fold decreased risk of graft failure and mortality 18-months post-transplantation, independently from age, gender, current cigarette smoking, anxiety symptoms, main primary diagnosis, UNOS score, number of comorbid diagnoses and history of transplantation. Data were consistent for liver and kidney transplantations. Other baseline predictive factors were: for graft failure, the main primary diagnosis and a shorter length since this diagnosis, and for mortality, older age, male gender and the main primary diagnosis. CONCLUSION: Further studies are needed to understand the underlying mechanisms of the association between report of depressive symptoms on waiting list and decreased risk of graft failure and mortality after transplantation