Timely HAART initiation may pave the way for a better viral control

<p>Abstract</p> <p>Background</p> <p>When to initiate antiretroviral therapy in HIV infected patients is a diffcult clinical decision. Actually, it is still a matter of discussion whether early highly active antiretroviral therapy (HAART) during primary HIV infection may influence the dynamics of the viral rebound, in case of therapy interruption, and overall the main disease course.</p> <p>Methods</p> <p>In this article we use a computational model and clinical data to identify the role of HAART timing on the residual capability to control HIV rebound after treatment suspension. Analyses of clinical data from three groups of patients initiating HAART respectively before seroconversion (very early), during the acute phase (early) and in the chronic phase (late), evidence differences arising from the very early events of the viral infection.</p> <p>Results</p> <p>The computational model allows a fine grain assessment of the impact of HAART timing on the disease outcome, from acute to chronic HIV-1 infection. Both patients' data and computer simulations reveal that HAART timing may indeed affect the HIV control capability after treatment discontinuation. In particular, we find a median time to viral rebound that is significantly longer in very early than in late patients.</p> <p>Conclusions</p> <p>A timing threshold is identified, corresponding to approximately three weeks post-infection, after which the capability to control HIV replication is lost. Conversely, HAART initiation occurring within three weeks from the infection could allow to preserve a significant control capability. This time could be related to the global triggering of uncontrolled immune activation, affecting residual immune competence preservation and HIV reservoir establishment.</p

Adolescent brain maturation and cortical folding: evidence for reductions in gyrification

Evidence from anatomical and functional imaging studies have highlighted major modifications of cortical circuits during adolescence. These include reductions of gray matter (GM), increases in the myelination of cortico-cortical connections and changes in the architecture of large-scale cortical networks. It is currently unclear, however, how the ongoing developmental processes impact upon the folding of the cerebral cortex and how changes in gyrification relate to maturation of GM/WM-volume, thickness and surface area. In the current study, we acquired high-resolution (3 Tesla) magnetic resonance imaging (MRI) data from 79 healthy subjects (34 males and 45 females) between the ages of 12 and 23 years and performed whole brain analysis of cortical folding patterns with the gyrification index (GI). In addition to GI-values, we obtained estimates of cortical thickness, surface area, GM and white matter (WM) volume which permitted correlations with changes in gyrification. Our data show pronounced and widespread reductions in GI-values during adolescence in several cortical regions which include precentral, temporal and frontal areas. Decreases in gyrification overlap only partially with changes in the thickness, volume and surface of GM and were characterized overall by a linear developmental trajectory. Our data suggest that the observed reductions in GI-values represent an additional, important modification of the cerebral cortex during late brain maturation which may be related to cognitive development

Engaging rural preceptors in new longitudinal community clerkships during workforce shortage: a qualitative study

Background: In keeping with its mission to produce doctors for rural and regional Australia, the University of Wollongong, Graduate School of Medicine has established an innovative model of clinical education. This includes a 12-month integrated community-based clerkship in a regional or rural setting, offering senior students longitudinal participation in a \u27community of practice\u27 with access to continuity of patient care experiences, continuity of supervision and curriculum, and individualised personal and professional development. This required developing new teaching sites, based on attracting preceptors and providing them with educational and physical infrastructure. A major challenge was severe health workforce shortages. Methods: Before the new clerkship started, we interviewed 28 general practitioners to determine why they engaged as clerkship preceptors. Independent researchers conducted semi-structured interviews. Responses were transcribed for inductive qualitative content analysis. Results: The new model motivated preceptors to engage because it enhanced their opportunities to contribute to authentic learning when compared with the perceived limitations of short-term attachments. Preceptors appreciated the significant recognition of the value of general practice teaching and the honour of major involvement in the university. They predicted that the initiative would have positive effects on general practitioner morale and improve the quality of their practice. Other themes included the doctors\u27 commitment to their profession, \u27handing on\u27 to the next generation and helping their community to attract doctors in the future. Conclusions: Supervisors perceive that new models of clinical education offer alternative solutions to health care education, delivery and workforce. The longitudinal relationship between preceptor, student and community was seen as offering reciprocal benefits. General practitioners are committed to refining practice and ensuring generation of new members in their profession. They are motivated to engage in novel regional and rural longitudinal clinical clerkships as they perceive that they offer students an authentic learning experience and are a potential strategy to help address workforce shortages and maldistribution

How does social integration influence breast cancer control among urban African-American women? Results from a cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>Although social integration is a well-established influence on health, less is known about how the specific types of social connection (social roles, social networks, and social support) influence knowledge, attitudes, and practices for specific prevention goals, and how to utilize these influences in interventions with priority populations. This research examined the prevalence of social roles, networks and support among 576 urban African-American women age 45–93 in East Baltimore, Maryland, and the association of these social factors with breast cancer related knowledge, attitudes, and practices.</p> <p>Methods</p> <p>Using data from 1997–1998 in-home interviews, we developed indices of six possible social roles, social networks of family, neighborhood and church, and instrumental and emotional social support. In multivariate models adjusting for age, education, and medical care, we examined the association of each social influence on breast cancer knowledge, attitudes, screening recency and intention, and treatment preferences.</p> <p>Results</p> <p>We found substantial variation in social integration among these women, with social integration positively associated with overall health and well-being. Social roles and networks were positively associated with screening knowledge, and emotional support and church networks were positively associated with attitudes conducive to early detection and treatment. In regard to screening behaviors, family networks were associated with both screening recency and intention. Women with greater church networks and emotional support held more conservative attitudes towards lumpectomy, reconstruction, and clinical trials.</p> <p>Conclusion</p> <p>Overall, social integration is a positive influence on breast cancer control and should be utilized where possible in interventions, including identifying surrogate mechanisms for support for subgroups without existing social resources.</p

The 9p21 susceptibility locus for coronary artery disease and the severity of coronary atherosclerosis

<p>Abstract</p> <p>Background</p> <p>Case-control Genome-Wide Association Studies (GWAS) have identified single nucleotide polymorphisms (SNPs) at the 9p21 locus as risk factors for coronary artery disease (CAD). The locus does not contain a clear candidate gene. Hence, the results of GWAS have raised an intense interest in delineating the basis for the observed association. We analyzed association of 4 SNPs at the 9p21 locus with the severity and progression of coronary atherosclerosis, as determined by serial quantitative coronary angiograms (QCA) in the well-characterized Lipoprotein Coronary Atherosclerosis Study (LCAS) population. The LCAS is a randomized placebo-control longitudinal follow-up study in patients with CAD conducted to test the effects of fluvastatin on progression or regression of coronary atherosclerosis.</p> <p>Methods</p> <p>Extensive plasma lipid levels were measured at the baseline and 2 1/2 years after randomization. Likewise serial QCA was performed at the baseline and upon completion of the study. We genotyped the population for 4 SNPs, previously identified as the susceptibility SNPs for CAD in GWAS, using fluorogenic 5' nuclease assays. We reconstructed the haplotypes using Phase 2, analyzed SNP and haplotype effects using the Thesias software as well as by the conventional statistical methods.</p> <p>Results</p> <p>Only Caucasians were included since they comprised 90% of the study population (332/371 with available DNA sample). The 4 SNPs at the 9p21 locus were in tight linkage disequilibrium, leading to 3 common haplotypes in the LCAS population. We found no significant association between quantitative indices of severity of coronary atherosclerosis, such as minimal lumen diameter and number of coronary lesions or occlusions and the 9p21 SNPs and haplotypes. Likewise, there was no association between quantitative indices of progression of coronary atherosclerosis and the SNPs or haplotypes. Similarly, we found no significant SNP or haplotype effect on severity and progression of coronary atherosclerosis.</p> <p>Conclusion</p> <p>We conclude the 4 SNPs at the 9p21 locus analyzed in this study do not impart major effects on the severity or progression of coronary atherosclerosis. The effect size may be very modest or the observed association of the CAD with SNPs at the 9p21 locus in the case-control GWAS reflect involvement of vascular mechanisms not directly related to the severity or progression of coronary atherosclerosis.</p

Early Outcomes of MDR-TB Treatment in a High HIV-Prevalence Setting in Southern Africa

BACKGROUND: Little is known about treatment of multidrug-resistant tuberculosis (MDR-TB) in high HIV-prevalence settings such as sub-Saharan Africa. METHODOLOGY/PRINCIPAL FINDINGS: We did a retrospective analysis of early outcomes of the first cohort of patients registered in the Lesotho national MDR-TB program between July 21, 2007 and April 21, 2008. Seventy-six patients were included for analysis. Patient follow-up ended when an outcome was recorded, or on October 21, 2008 for those still on treatment. Fifty-six patients (74%) were infected with HIV; the median CD4 cell count was 184 cells/microl (range 5-824 cells/microl). By the end of the follow-up period, study patients had been followed for a median of 252 days (range 12-451 days). Twenty-two patients (29%) had died, and 52 patients (68%) were alive and in treatment. In patients who did not die, culture conversion was documented in 52/54 patients (96%). One patient had defaulted, and one patient had transferred out. Death occurred after a median of 66 days in treatment (range 12-374 days). CONCLUSIONS/SIGNIFICANCE: In a region where clinicians and program managers are increasingly confronted by drug-resistant tuberculosis, this report provides sobering evidence of the difficulty of MDR-TB treatment in high HIV-prevalence settings. In Lesotho, an innovative community-based treatment model that involved social and nutritional support, twice-daily directly observed treatment and early empiric use of second-line TB drugs was successful in reducing mortality of MDR-TB patients. Further research is urgently needed to improve MDR-TB treatment outcomes in high HIV-prevalence settings

Is there a role of statins in the prevention of aortic biological prostheses degeneration

It has been recently observed that statins might slow the progression of aortic stenosis or sclerosis. Preliminary reports suggested a similar positive effect in reducing the degeneration of aortic valve bioprostheses even though this hypothesis should be further proven and supported by new data. In this review the present evidences of the possible effects of statins in this field are discussed

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

Lacticacidaemia due to pyruvate dehydrogenase deficiency, with evidence of protein polymorphism in the α-subunit of the enzyme

In three infants with neonatal lacticacidaemia, a deficiency in the E 1 (pyruvate dehydrogenase) component of the pyruvate dehydrogenase complex was demonstrated in skin fibroblast cultures. Residual activites of the pyruvate dehydrogenase complex in the activated state were 1.6%, 3.9% and 18.8% of control values, respectively. Immunoprecipitation of extracts of cultures skin fibroblasts grown on 35 S-methionine with anti-pyruvate dehydrogenase complex antibody revealed an abnormality in the E 1 α-component of these three patients when visualised after sodium dodecyl sulphate/polyacrylamide gel electrophoresis. This component appeared to have a slightly lower molecular weight than did this protein from control cell strains. Cell strains from other patients with a deficiency of the pyruvate dehydrogenase complex did not exhibit this defect. Three patients also showed dysmorphism and developmental abnormalities of the central nervous system.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47532/1/431_2004_Article_BF00441736.pd