Role of extracellular phospholipases and mononuclear phagocytes in dissemination of cryptococcosis in a murine model

Secreted phospholipase B (PLB) activity promotes the survival and replication of Cryptococcus neoformans in macrophages in vitro. We therefore investigated the role of mononuclear phagocytes and cryptococcal PLB in the dissemination of infection in a mouse model, using C. neoformans var. grubii wild-type strain H99, a PLB1 deletion mutant (Delta plb1), and a reconstituted strain (Delta plb1(rec)). PLB facilitated the entry of endotracheally administered cryptococci into lung IM. PLB was also required for lymphatic spread from the lung to regional lymph nodes and for entry into the blood. Langhans-type giant cells containing budding cryptococci were seen free in the lymphatic sinuses of hilar nodes of H99- and Delta plb1(rec)-infected mice, suggesting that they may have a role in the dissemination of cryptococcal infection. The transfer of infected lung macrophages to recipient mice by tail vein injections demonstrated that these cells can facilitate hematogenous dissemination of cryptococci to the brain, independent of cryptococcal PLB secretion. PLB activities of cryptococci isolated from lung macrophages or infected brains were not persistently increased. We conclude that mononuclear phagocytes are a vehicle for cryptococcal dissemination and that PLB activity is necessary for the initiation of interstitial pulmonary infections and for dissemination from the lung via the lymphatics and blood. PLB is not, however, essential for the establishment of neurological infections when cryptococci are presented within, or after passage through, mononuclear phagocytes.     

Gender identity in XY intersexuality

The following syndromes of XY intersexuality are reviewed: 5alpha-reductase-2 deficiency, 17beta-hydroxysteroid dehydrogenase-3 deficiency, and complete and partial androgen insensitivity with attention focused on issues of gender identity. Each syndrome, with its unique presentation, provides an opportunity to explore the relative effects of nature (androgens) versus nurture (sex of rearing) in gender identity development. The phenomenon of gender role reversal in these conditions is described and theories on the determinants of gender identity formation are proposed. Issues of importance to psychiatrists in treating patients who have these conditions also are discussed.     

A double blind,randomized, placebo-controlled trial of proton pump inhibitor therapy in patients with uninvestigated dyspepsia

OBJECTIVES: In patients with uninvestigated dyspepsia, a common initial management strategy in primary care is to prescribe a course of empiric antisecretory therapy and to refer those patients who do not respond for endoscopy. The objective of this research was to evaluate the effects of an empiric course of antisecretory therapy on dyspepsia-related health in patients with uninvestigated dyspepsia. METHODS: We conducted a double blind, randomized, placebo-controlled trial in which patients with uninvestigated dyspepsia were randomized to a 6-wk course of omeprazole 20 mg p.o. b.id. versus placebo capsules p.o. bi.d. and followed over 1 yr. The patients were at least 18 yr old with at least a 1-wk history of dyspepsia without alarm features. Dyspepsia-related health was measured using the Severity of Dyspepsia Assessment (SODA), a valid, reliable, disease-specific outcome measure. The primary outcome was treatment failure, defined by a SODA Pain Intensity score > or = 29 (scores, 2-47) during follow-up. Patients who were treatment failures underwent endoscopy. RESULTS: We enrolled 140 patients. The mean age was 51 yr, and seven (5%) were women. At 2 wk there were fewer treatment failures in the omeprazole group: 12 of 71 patients (17%) in the omeprazole group failed compared with 24 of 69 (35%) in the placebo group (p = 0.037, log rank test). Also, at 6 wk there were fewer failures in the omeprazole group: 21 of 71 patients (30%) in the omeprazole group failed compared with 31 of 69 (45%) in the placebo group in 0.067, log rank test). However, at the 1-yr follow-up, there was no significant difference in treatment failure rates in the two groups: 37 of 71 patients (52%) in the omeprazole group failed compared with 41 of 69 (59%) in the placebo group (p = 0.28, log rank test). CONCLUSIONS: In patients with uninvestigated dyspepsia, as compared with a strategy that would entail prompt endoscopy for all patients, an initial 6-wk course of either placebo or omeprazole reduces the need for endoscopy over a 1-yr follow-up. Compared with placebo, an initial 6-wk course of omeprazole delays, but does not reduce, the need for endoscopy. For proton pump inhibitor therapy to reduce the need for endoscopy, it may need to be given continuously.     

What nurses say they do and need: implications for the educational preparation of nurses

The scope of contemporary nursing is a critical factor in determining the appropriate educational preparation of nurses today and in the future. This qualitative study involved interviewing nurses throughout Australia in a variety of work and geographical settings to develop a snapshot of what nurses are doing, the skills needed and the challenges faced.The snapshot of contemporary practice that emerged is one of considerable diversity, which poses challenges for educators of nurses in terms of what constitutes appropriate or adequate educational preparation for nurses. Understandings of what constitutes clinical skills, and consequently clinical education, are explored as is what calls for 'more' clinical education may actually mean. Caution is raised about educating for present needs that are based on limited conceptions of what constitutes a nursing workplace. It is argued that education for nurses, both initial and on going, must be cognizant of educating for what might be, not simply somewhat short-term imperatives.     

Indocyanine green loaded hyaluronan-derived nanoparticles for fluorescence-enhanced surgical imaging of pancreatic cancer

Pancreatic ductal adenocarcinoma is highly lethal and surgical resection is the only potential curative treatment for the disease. In this study, hyaluronic acid derived nanoparticles with physico-chemically entrapped indocyanine green, termed NanoICG, were utilized for intraoperative near infrared fluorescence detection of pancreatic cancer. NanoICG was not cytotoxic to healthy pancreatic epithelial cells and did not induce chemotaxis or phagocytosis, it accumulated significantly within the pancreas in an orthotopic pancreatic ductal adenocarcinoma model, and demonstrated contrast-enhancement for pancreatic lesions relative to non-diseased portions of the pancreas. Fluorescence microscopy showed higher fluorescence intensity in pancreatic lesions and splenic metastases due to NanoICG compared to ICG alone. The in vivo safety profile of NanoICG, including, biochemical, hematological, and pathological analysis of NanoICG-treated healthy mice, indicates negligible toxicity. These results suggest that NanoICG is a promising contrast agent for intraoperative detection of pancreatic tumors.     

Relationship Education for Youth in High School: Preliminary Evidence from a Non-controlled Study on Dating Behavior and Parent–Adolescent Relationships

Background

Relationship education (RE), often employed for adults, has become increasingly available for teenagers. However, non-romantic relationships are rarely assessed as a potential outcome domain influenced by RE.

Objective

Informed by life course theory and the ecological systems perspective, this study examines the influence of RE on both dating and parent–adolescent relationships, and the associations between such changes.

Methods

Using a one-sample, non-controlled design, we conducted repeated measures analysis of covariance, and hierarchical linear regression analyses to examine the influence of RE participation on 3658 ethnically diverse adolescents’ knowledge and use of healthy skills in their parent–adolescent and dating relationships and whether these changes are linked.

Results

Results indicate significant and positive influences on participants’ knowledge and use of healthy relationship skills in their parent–adolescent and dating relationships. Further, results indicate that change in the current dating relationship is associated with concurrent change in the parent–adolescent relationship.

Conclusion

The results of this study provide preliminary evidence for a spillover effect of relationship education efforts, which are traditionally focused on the youth dating relationships, to parent–adolescent relationship dynamics. Future research considering multiple domains of RE outcomes for youth is warranted and future RE development and implementation may consider integrating parents to maximize program outcomes.