Non-Human Primate Model of Kaposi's Sarcoma-Associated Herpesvirus Infection

Since Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8) was first identified in Kaposi's sarcoma (KS) lesions of HIV-infected individuals with AIDS, the basic biological understanding of KSHV has progressed remarkably. However, the absence of a proper animal model for KSHV continues to impede direct in vivo studies of viral replication, persistence, and pathogenesis. In response to this need for an animal model of KSHV infection, we have explored whether common marmosets can be experimentally infected with human KSHV. Here, we report the successful zoonotic transmission of KSHV into common marmosets (Callithrix jacchus, Cj), a New World primate. Marmosets infected with recombinant KSHV rapidly seroconverted and maintained a vigorous anti-KSHV antibody response. KSHV DNA and latent nuclear antigen (LANA) were readily detected in the peripheral blood mononuclear cells (PBMCs) and various tissues of infected marmosets. Remarkably, one orally infected marmoset developed a KS-like skin lesion with the characteristic infiltration of leukocytes by spindle cells positive for KSHV DNA and proteins. These results demonstrate that human KSHV infects common marmosets, establishes an efficient persistent infection, and occasionally leads to a KS-like skin lesion. This is the first animal model to significantly elaborate the important aspects of KSHV infection in humans and will aid in the future design of vaccines against KSHV and anti-viral therapies targeting KSHV coinfected tumor cells

Two common nonsynonymous paraoxonase 1 (PON1) gene polymorphisms and brain astrocytoma and meningioma

<p>Abstract</p> <p>Background</p> <p>Human serum paraoxonase 1 (PON1) plays a major role in the metabolism of several organophosphorus compounds. The enzyme is encoded by the polymorphic gene <it>PON1</it>, located on chromosome 7q21.3. Aiming to identify genetic variations related to the risk of developing brain tumors, we investigated the putative association between common nonsynonymous <it>PON1 </it>polymorphisms and the risk of developing astrocytoma and meningioma.</p> <p>Methods</p> <p>Seventy one consecutive patients with brain tumors (43 with astrocytoma grade II/III and 28 with meningioma) with ages ranging 21 to 76 years, and 220 healthy controls subjects were analyzed for the frequency of the nonsynonymous <it>PON1 </it>genotypes L55M rs854560 and Q192R rs662. All participants were adult Caucasian individuals recruited in the central area of Spain.</p> <p>Results</p> <p>The frequencies of the <it>PON1 </it>genotypes and allelic variants of the polymorphisms <it>PON1 </it>L55M and <it>PON1 </it>Q192R did not differ significantly between patients with astrocytoma and meningioma and controls. The minor allele frequencies were as follows: <it>PON1 </it>55L, 0.398, 0.328 and 0.286 for patients with astrocytoma, meningioma and control individuals, respectively; <it>PON1 </it>192R, 0.341, 0.362 and 0.302 for patients with astrocytoma, meningioma and control individuals, respectively. Correction for age, gender, or education, made no difference in odds ratios and the <it>p </it>values remained non-significant. Haplotype association analyses did not identify any significant association with the risk of developing astrocytoma or meningioma.</p> <p>Conclusions</p> <p>Common nonsynonymous <it>PON1 </it>polymorphisms are not related with the risk of developing astrocytoma and meningioma.</p

Medication adherence perspectives in haemodialysis patients: a qualitative study

Background: End-stage kidney disease patients undergoing haemodialysis are prescribed with multiple complex regimens and are predisposed to high risk of medication nonadherence. The aims of this study were to explore factors associated with medication adherence, and, to examine the differential perspectives on medication-taking behaviour shown by adherent and nonadherent haemodialysis patients. Methods: A qualitative exploratory design was used. One-on-one semi-structured interviews were conducted with 30 haemodialysis patients at the outpatient dialysis facility in Hobart, Australia. Patient self-reported adherence was measured using 4-item Morisky Green Levine scale. Interview transcripts were thematically analysed and mapped against the World Health Organization (WHO) determinants of medication adherence. Results: Participants were 44–84 years old, and were prescribed with 4–19 medications daily. More than half of the participants were nonadherent to their medications based on self-reported measure (56.7%, n = 17). Themes mapped against WHO adherence model comprised of patient-related (knowledge, awareness, attitude, self-efficacy, action control, and facilitation); health system/ healthcare team related (quality of interaction, and mistrust and collateral arrangements); therapy-related (physical characteristics of medicines, packaging, and side effects); condition-related (symptom severity); and social/ economic factors (access to medicines, and relative affordability). Conclusions: Patients expressed a number of concerns that led to nonadherence behaviour. Many of the issues identified were patient-related and potentially modifiable by using psycho-educational or cognitive-behavioural interventions. Healthcare professionals should be more vigilant towards identifying these concerns to address adherence issues. Future research should be aimed at understanding healthcare professionals’ perceptions and practices of assessing medication adherence in dialysis patients that may guide intervention to resolve this significant issue of medication non-adherence