Murine Leukemia Virus Spreading in Mice Impaired in the Biogenesis of Secretory Lysosomes and Ca2+-Regulated Exocytosis

Retroviruses have been observed to bud intracellularly into multivesicular bodies (MVB), in addition to the plasma membrane. Release from MVB is thought to occur by Ca(2+)-regulated fusion with the plasma membrane.To address the role of the MVB pathway in replication of the murine leukemia virus (MLV) we took advantage of mouse models for the Hermansky-Pudlak syndrome (HPS) and Griscelli syndrome. In humans, these disorders are characterized by hypopigmentation and immunological alterations that are caused by defects in the biogenesis and trafficking of MVBs and other lysosome related organelles. Neonatal mice for these disease models lacking functional AP-3, Rab27A and BLOC factors were infected with Moloney MLV and the spread of virus into bone marrow, spleen and thymus was monitored. We found a moderate reduction in MLV infection levels in most mutant mice, which differed by less than two-fold compared to wild-type mice. In vitro, MLV release form bone-marrow derived macrophages was slightly enhanced. Finally, we found no evidence for a Ca(2+)-regulated release pathway in vitro. Furthermore, MLV replication was only moderately affected in mice lacking Synaptotagmin VII, a Ca(2+)-sensor regulating lysosome fusion with the plasma membrane.Given that MLV spreading in mice depends on multiple rounds of replication even moderate reduction of virus release at the cellular level would accumulate and lead to a significant effect over time. Thus our in vivo and in vitro data collectively argue against an essential role for a MVB- and secretory lysosome-mediated pathway in the egress of MLV

Treatment of acute diverticulitis laparoscopic lavage vs. resection (DILALA): study protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Perforated diverticulitis is a condition associated with substantial morbidity. Recently published reports suggest that laparoscopic lavage has fewer complications and shorter hospital stay. So far no randomised study has published any results.</p> <p>Methods</p> <p>DILALA is a Scandinavian, randomised trial, comparing laparoscopic lavage (LL) to the traditional Hartmann's Procedure (HP). Primary endpoint is the number of re-operations within 12 months. Secondary endpoints consist of mortality, quality of life (QoL), re-admission, health economy assessment and permanent stoma. Patients are included when surgery is required. A laparoscopy is performed and if Hinchey grade III is diagnosed the patient is included and randomised 1:1, to either LL or HP. Patients undergoing LL receive > 3L of saline intraperitoneally, placement of pelvic drain and continued antibiotics. Follow-up is scheduled 6-12 weeks, 6 months and 12 months. A QoL-form is filled out on discharge, 6- and 12 months. Inclusion is set to 80 patients (40+40).</p> <p>Discussion</p> <p>HP is associated with a high rate of complication. Not only does the primary operation entail complications, but also subsequent surgery is associated with a high morbidity. Thus the combined risk of treatment for the patient is high. The aim of the DILALA trial is to evaluate if laparoscopic lavage is a safe, minimally invasive method for patients with perforated diverticulitis Hinchey grade III, resulting in fewer re-operations, decreased morbidity, mortality, costs and increased quality of life.</p> <p>Trial registration</p> <p>British registry (ISRCTN) for clinical trials <a href="http://www.controlled-trials.com/ISRCTN82208287">ISRCTN82208287</a><url>http://www.controlled-trials.com/ISRCTN82208287</url></p

The X-ray source population of the globular cluster M15: Chandra high resolution imaging

The globular cluster M15 was observed on three occasions with the High Resolution Camera on board Chandra in 2001 in order to investigate the X-ray source population in the cluster centre. After subtraction of the two bright central sources, four faint sources were identified within 50 arcsec of the core. One of these sources is probably the planetary nebula, K648, making this the first positive detection of X-rays from a planetary nebula inside a globular cluster. Another two are identified with UV variables (one previously known), which we suggest are cataclysmic variables (CVs). The nature of the fourth source is more difficult to ascertain, and we discuss whether it is possibly a quiescent soft X-ray transient (qSXT) or also a CV.Comment: 9 pages, 6 figures, accepted for publication in MNRAS. Original figures can be obtained from http://www.astro.helsinki.fi/~diana/M15.htm

Pre-post changes in psychosocial functioning among relatives of patients with depressive disorders after Brief Multifamily Psychoeducation: A pilot study

<p>Abstract</p> <p>Background</p> <p>Depressive disorder is often chronic and recurrent, and results in a heavy psychosocial burden on the families of patients with this disorder. This study aims to examine the effectiveness of brief multifamily psychoeducation designed to alleviate their psychosocial burden.</p> <p>Methods</p> <p>Thirty-two relatives of patients with major depressive disorder participated in an open study testing the effectiveness of brief multifamily psychoeducation. The intervention consisted of four sessions over the course of 6 weeks. Outcome measures focused on emotional distress, care burden and Expressed Emotion (EE).</p> <p>Results</p> <p>The emotional distress, care burden and EE of the family all showed statistically significant improvements from baseline to after the family intervention. The proportion of relatives scoring 9 or more on K6, which indicates possible depressive or anxiety disorder, decreased from sixteen relatives (50.0%) at baseline, to only 3 relatives (9.3%) after the intervention.</p> <p>Conclusions</p> <p>This study suggests that brief multifamily psychoeducation is a useful intervention to reduce the psychosocial burden of the relatives of patients with depressive disorder. Further evaluation of family psychoeducation for relatives of patients with depressive disorder is warranted.</p

Problem and solution: The spiritual dimension of clergy sexual abuse and its impact on survivors

In this paper, we offer a way to understand the spiritual dimension of clergy-perpetrated sexual abuse. Spirituality is defined as a search for the sacreda process of discovery, conservation, and transformation that evolves over the lifespan. We describe the ways in which clergy-perpetrated sexual abuse impacts negatively on the individual\u27s search for the sacred and the ways in which spirituality can serve as a valuable resource for survivors. We then consider how clinicians can draw on the client\u27s spirituality as a source of solutions to problems and how clinicians can address the spiritual problems raised by clergy-perpetrated sexual abuse. Perhaps the greatest challenge for mental health professionals is to become better acquainted with the multifaceted nature of spiritual life. © 2008 by The Haworth Press. All rights reserved