Exposure to ultraviolet B did not lower blood pressure. Our results suggest that if vitamin D protects against cardiovascular disease, it involves some mechanism other than blood pressure.

No abstract

The full repertoire of hepatitis B virus (HBV) peptides that bind to the common HLA class I molecules found in areas with a high prevalence of chronic HBV infection has not been determined. This information may be useful for designing immunotherapies for chronic hepatitis B. We identified amino acid residues under positive selection pressure in the HBV core gene by phylogenetic analysis of cloned DNA sequences obtained from HBV DNA extracted from the sera of Tongan subjects with inactive, HBeAg-negative chronic HBV infections. The repertoires of positively selected sites in groups of subjects who were homozygous for either HLA-B*4001 (n ‫؍‬ 10) or HLA-B*5602 (n ‫؍‬ 7) were compared. We identified 13 amino acid sites under positive selection pressure. A significant association between an HLA class I allele and the presence of nonsynonymous mutations was found at five of these sites. HLA-B*4001 was associated with mutations at E77 (P ‫؍‬ 0.05) and E113 (P ‫؍‬ 0.002), and HLA-B*5602 was associated with mutations at S21 (P ‫؍‬ 0.02). In addition, amino acid mutations at V13 (P ‫؍‬ 0.03) and E14 (P ‫؍‬ 0.01) were more common in the seven subjects with an HLA-A*02 allele. In summary, we have developed an assay that can identify associations between HLA class I alleles and HBV core gene amino acids that mutate in response to selection pressure. This is consistent with published evidence that CD8 ؉ T cells have a role in suppressing viral replication in inactive, HBeAg-negative chronic HBV infection. This assay may be useful for identifying the clinically significant HBV peptides that bind to common HLA class I molecules.The most potent nucleoside/nucleotide analogue drugs used to treat chronic hepatitis B reduce serum hepatitis B virus (HBV) DNA to undetectable levels in over 90% of subjects (5, 10). It was originally hoped that such a substantial reduction in viral titers would reverse T-cell tolerance for HBV antigens (17, 30) and lead to an immune response that permanently suppressed the virus, thus removing the need for expensive, lifelong drug therapy. However, HBeAg seroconversion rates of under 30% suggest that suppression of HBV replication is not sufficient to reverse the defects (4, 15) in the HBV peptidespecific CD8 ϩ T-cell compartment that occur in these patients. A therapeutic vaccine that stimulated a diverse repertoire of functional CD8 ϩ T cells could make a valuable contribution to management of chronic hepatitis B.The first step in designing a therapeutic vaccine that will suppress viral replication without exacerbating chronic hepatitis B (15) is to identify the HBV peptides that stimulate functional CD8 ϩ T cells by binding to the most common HLA class I alleles. These peptides may contribute to the antigen component of a vaccine and to the design of assays for use as correlates of immunity in trials of antiviral therapies. Although some of the HBV peptides that bind to four HLA-A alleles have been published (3,19,25,28), a much wider repertoire of peptide-HLA interactions needs to be identified. T...

BackgroundGout treatment is suboptimal despite available therapy, with low levels of initiation and persistence of urate-lowering therapy (ULT) in many patients.AimTo identify all interventions that have attempted to improve the uptake of ULT and analyse the clinical outcomes.Design & settingA systematic review of international articles published in English.MethodA systematic search was conducted through MEDLINE, Embase, CINAHL Plus, and Scopus databases to identify all studies on relevant interventions for gout. Interventions were included if they aimed to address patient adherence with serum urate (SU) level as an outcome. This included patient education, practitioner monitoring, medication titration, SU monitoring, and ongoing patient engagement and follow-up. Follow-up studies to original interventions and those with only an abstract available were included.ResultsTwenty articles met the inclusion criteria, describing outcomes of 18 interventions conducted in primary care settings: six nurse-led, five pharmacist-led, and seven multidisciplinary, multifaceted interventions. Improvement in SU levels was observed in all interventions. Nurse-led interventions were effective at empowering patients as they addressed illness perceptions and provided education, advice, and telephone follow-up. Pharmacist-led interventions primarily aimed to monitor patients, alter medication dosage, and provide automated telephone follow-up. Various multifaceted programmes involving a range of providers resulted in increased sustained use of urate-lowering medication.ConclusionA nurse-led approach focusing on patient understanding about gout is the most effective in achieving improved patient adherence, and lowered SU levels among patients. An intervention should include patient education and follow-up components.

While typically North American and Anglo-European stances have dominated discussion on different paradigms advanced about mixed method research, recently there has been a call for examination of other cultural worldviews. This article contributes to the field of mixed methods research by presenting a worldview based on collective inquiry, whereby different perspectives are woven together to create new knowledge. Fa’afaletui, a Samoan research framework, literally means “‘ways of’ [fa’a] ‘weaving together’ [tui] deliberations of different groups or ‘houses’ [fale].” It is derived from the Pacific philosophy of connectiveness and a collective holistic approach. We give a case example of how this framework is directing our research.