Pharmacy ethical reasoning: a comparison of Australian pharmacists and interns

International Journal of Clinical Pharmacy - Background Ethical reasoning informs decision making and professional judgement, is guided by codes of ethics and conduct, and requires navigation...     

CD81-Receptor Associations — Impact for Hepatitis C Virus Entry and Antiviral Therapies

Tetraspanins are integral transmembrane proteins organized in microdomains displaying specific and direct interactions with other tetraspanins and molecular partners. Among them, CD81 has been implicated in a variety of physiological and pathological processes. CD81 also plays a crucial role in pathogen entry into host cells, including hepatitis C virus (HCV) entry into hepatocytes. HCV is a major cause of liver cirrhosis and hepatocellular carcinoma. HCV entry into hepatocytes is a complex process that requires the coordinated interaction of viral and host factors for the initiation of infection, including CD81, scavenger receptor BI, claudin-1, occludin, membrane-bound host cell kinases, Niemann-Pick C1 Like 1, Harvey rat sarcoma viral oncogene homolog (HRas), CD63 and transferrin receptor 1. Furthermore, recent data in HCV model systems have demonstrated that targeting critical components of tetraspanins and associated cell membrane proteins open new avenues to prevent and treat viral infection.     

Incidence and Characteristics of Atypical Femoral Fractures: Clinical and Geometrical Data

Despite the multitude of studies published on atypical femoral fractures (AFFs), a profile for patients at risk does not exist. This study aimed first at estimating AFF incidence over a 19‐month‐period in Quebec City using the ASBMR Task force criteria to define AFF. The medical records of patients hospitalized for hip or femoral fracture between June 1, 2009, and December 31, 2010, were reviewed. Thirty‐six cases of atypical fractures were identified during the 19‐month period, representing an AFF incidence of 7.0 (range, 4.7 to 9.3) cases per 100,000 person‐years. In the second part of the study, data regarding the characteristics suspected of increasing the risks of AFF were collected from medical and pharmacological records, proximal femur radiographs, and patient interviews. The data regarding each patient with an AFF during years 2008‐2011 were compared to two controls with a hip or femoral fragility fracture or a traumatic fracture, paired for age and sex. Twenty patients with AFF were added to the 36 patients with AFF selected in the first part, thereby 56 patients with AFF were investigated. The association between the occurrence of AFF and bisphosphonates (BPs) use was proven statistically significant in multivariate analysis, odds ratio (OR) = 10.39 (95% CI, 2.22 to 48.58; p = 0.0029). Compared to controls, patients with AFF had excessive femoral offset (43.1 mm versus 38.3 mm, p = 0.0007), proximal femoral neck angle in varus (128.9 degrees versus 134.0 degrees, p < 0.0001), and had greater proximal cortical thickness. This retrospective study confirms the low incidence of AFF, confirms its significant association with exposure to BPs, and reveals the possible contribution of proximal femoral geometry in AFF occurrence. © 2016 American Society for Bone and Mineral Research.     

Invariant and noninvariant natural killer T cells exert opposite regulatory functions on the immune response during murine schistosomiasis

CD1d-restricted natural killer T (NKT) cells represent a heterogeneous population of innate memory immune cells expressing both NK and T-cell markers distributed into two major subsets, i.e., invariant NKT (iNKT) cells, which express exclusively an invariant T-cell receptor (TCR) alpha chain (Valpha14Jalpha18 in mice), and non-iNKT cells, which express more diverse TCRs. NKT cells quickly produce Th1- and/or Th2-type cytokines following stimulation with glycolipid antigen (Ag) and, through this property, play potent immunoregulatory roles in autoimmune diseases, cancer, and infection. No study has addressed the role of NKT cells in metazoan parasite infections so far. We show that during murine schistosomiasis, the apparent frequency of both iNKT cells and non-iNKT cells decreased in the spleen as early as 3 weeks postinfection (p.i.) and that both populations expressed a greater amount of the activation marker CD69 at 6 weeks p.i., suggesting an activated phenotype. Two different NKT-cell-deficient mouse models, namely, TCR Jalpha18-/- (exclusively deficient in iNKT cells) and CD1d-/- (deficient in both iNKT and non-iNKT cells) mice, were used to explore the implication of these subsets in infection. We show that whereas both iNKT and non-iNKT cells do not have a major impact on the immune response during the early phase (1 and 4 weeks) of infection, they exert important, although opposite, effects on the immune response during the acute phase of the disease (7 and 12 weeks), after schistosome egg production. Indeed, iNKT cells contribute to Th1 cell differentiation whereas non-iNKT cells might be mostly implicated in Th2 cell differentiation in response to parasite Ag. Our findings suggest, for the first time, that helminths activate both iNKT and non-iNKT cells in vivo, enabling them to differentially influence the Th1/Th2 balance of the immune response.