Neurocognitive function in HIV infected patients on antiretroviral therapy

OBJECTIVE To describe factors associated with neurocognitive (NC) function in HIV-positive patients on stable combination antiretroviral therapy. DESIGN We undertook a cross-sectional analysis assessing NC data obtained at baseline in patients entering the Protease-Inhibitor-Monotherapy-Versus-Ongoing-Triple therapy (PIVOT) trial. MAIN OUTCOME MEASURE NC testing comprised of 5 domains. Raw results were z-transformed using standard and demographically adjusted normative datasets (ND). Global z-scores (NPZ-5) were derived from averaging the 5 domains and percentage of subjects with test scores >1 standard deviation (SD) below population means in at least two domains (abnormal Frascati score) calculated. Patient characteristics associated with NC results were assessed using multivariable linear regression. RESULTS Of the 587 patients in PIVOT, 557 had full NC results and were included. 77% were male, 68% Caucasian and 28% of Black ethnicity. Mean (SD) baseline and nadir CD4+ lymphocyte counts were 553(217) and 177(117) cells/µL, respectively, and HIV RNA was <50 copies/mL in all. Median (IQR) NPZ-5 score was -0.5 (-1.2/-0) overall, and -0.3 (-0.7/0.1) and -1.4 (-2/-0.8) in subjects of Caucasian and Black ethnicity, respectively. Abnormal Frascati scores using the standard-ND were observed in 51%, 38%, and 81%, respectively, of subjects overall, Caucasian and Black ethnicity (p<0.001), but in 62% and 69% of Caucasian and Black subjects using demographically adjusted-ND (p = 0.20). In the multivariate analysis, only Black ethnicity was associated with poorer NPZ-5 scores (P<0.001). CONCLUSIONS In this large group of HIV-infected subjects with viral load suppression, ethnicity but not HIV-disease factors is closely associated with NC results. The prevalence of abnormal results is highly dependent on control datasets utilised. TRIAL REGISTRY ClinicalTrials.gov, NCT01230580

Private patient perceptions about a public programme; what do private Indian tuberculosis patients really feel about directly observed treatment?

<p>Abstract</p> <p>Background</p> <p>India accounts for one-fifth of the global incident cases of tuberculosis(TB). The country presently has the world's largest directly observed treatment, short course (DOTS) programme, that has shown impressive results and covers almost 100% of the billion-plus Indian population. Despite such a successful programme, the majority of Indian patients with tuberculosis prefer private healthcare, although repeated audits of this sector have shown the quality to be poor.</p> <p>We aimed to ascertain the level of awareness and knowledge of private patients with tuberculosis attending our clinic at a tertiary private healthcare institute with regards to the DOTS programme, understanding the reasons behind their preference for private healthcare, and evaluating their perceptions and reasons for accepting or failing to accept directly observed therapy as a treatment option.</p> <p>Methods</p> <p>A structured interview schedule was administered to private patients with tuberculosis at the P.D. Hinduja Hospital and Medical Research Centre, Mumbai, India between January 2006 to November 2007.</p> <p>Results</p> <p>Only 30 of 200 patients (15%) were aware of the DOTS programme. After being explained what directly observed therapy was, 136 patients (68%) found this form of treatment unacceptable.183 patients (91.5%) preferred buying the drugs themselves to visiting a DOTS centre. 90 patients (45%) were not prepared to be observed while swallowing their TB drugs, finding it an intrusion of privacy.</p> <p>Conclusions</p> <p>Our study reveals a poor knowledge and awareness of the DOTS programme among the cohort of TB patients that we interviewed. The control of TB in India will undoubtedly benefit from more patients being attracted to and treated by the existing DOTS programmes. However, directly observed treatment, in its present form, is considered too rigid and intrusive and is unlikely to be accepted by a majority of patients seeking private healthcare. Novel strategies and more flexible options will have to be devised to ensure higher cure rates without compromising patient choice.</p

MutLα heterodimers modify the molecular phenotype of Friedreich ataxia

This article has been made available through the Brunel Open Access Publishing Fund.Background: Friedreich ataxia (FRDA), the most common autosomal recessive ataxia disorder, is caused by a dynamic GAA repeat expansion mutation within intron 1 of FXN gene, resulting in down-regulation of frataxin expression. Studies of cell and mouse models have revealed a role for the mismatch repair (MMR) MutS-heterodimer complexes and the PMS2 component of the MutLα complex in the dynamics of intergenerational and somatic GAA repeat expansions: MSH2, MSH3 and MSH6 promote GAA repeat expansions, while PMS2 inhibits GAA repeat expansions. Methodology/Principal Findings: To determine the potential role of the other component of the MutLα complex, MLH1, in GAA repeat instability in FRDA, we have analyzed intergenerational and somatic GAA repeat expansions from FXN transgenic mice that have been crossed with Mlh1 deficient mice. We find that loss of Mlh1 activity reduces both intergenerational and somatic GAA repeat expansions. However, we also find that loss of either Mlh1 or Pms2 reduces FXN transcription, suggesting different mechanisms of action for Mlh1 and Pms2 on GAA repeat expansion dynamics and regulation of FXN transcription. Conclusions/Significance: Both MutLα components, PMS2 and MLH1, have now been shown to modify the molecular phenotype of FRDA. We propose that upregulation of MLH1 or PMS2 could be potential FRDA therapeutic approaches to increase FXN transcription. © 2014 Ezzatizadeh et al.This article has been made available through the Brunel Open Access Publishing Fund

Patients' Costs and Cost-Effectiveness of Tuberculosis Treatment in DOTS and Non-DOTS Facilities in Rio de Janeiro, Brazil

Costs of tuberculosis diagnosis and treatment may represent a significant burden for the poor and for the health system in resource-poor countries.The aim of this study was to analyze patients' costs of tuberculosis care and to estimate the incremental cost-effectiveness ratio (ICER) of the directly observed treatment (DOT) strategy per completed treatment in Rio de Janeiro, Brazil.We interviewed 218 adult patients with bacteriologically confirmed pulmonary tuberculosis. Information on direct (out-of-pocket expenses) and indirect (hours lost) costs, loss in income and costs with extra help were gathered through a questionnaire. Healthcare system additional costs due to supervision of pill-intake were calculated considering staff salaries. Effectiveness was measured by treatment completion rate. The ICER of DOT compared to self-administered therapy (SAT) was calculated.DOT increased costs during the treatment phase, while SAT increased costs in the pre-diagnostic phase, for both the patient and the health system. Treatment completion rates were 71% in SAT facilities and 79% in DOT facilities. Costs per completed treatment were US$194 for patients and U$ 189 for the health system in SAT facilities, compared to US$336 and US$ 726 in DOT facilities. The ICER was US$ 6,616 per completed DOT treatment compared to SAT.Costs incurred by TB patients are high in Rio de Janeiro, especially for those under DOT. The DOT strategy doubles patients' costs and increases by fourfold the health system costs per completed treatment. The additional costs for DOT may be one of the contributing factors to the completion rates below the targeted 85% recommended by WHO

Single electron emission in two-phase xenon with application to the detection of coherent neutrino-nucleus scattering

We present an experimental study of single electron emission in ZEPLIN-III, a two-phase xenon experiment built to search for dark matter WIMPs, and discuss applications enabled by the excellent signal-to-noise ratio achieved in detecting this signature. Firstly, we demonstrate a practical method for precise measurement of the free electron lifetime in liquid xenon during normal operation of these detectors. Then, using a realistic detector response model and backgrounds, we assess the feasibility of deploying such an instrument for measuring coherent neutrino-nucleus elastic scattering using the ionisation channel in the few-electron regime. We conclude that it should be possible to measure this elusive neutrino signature above an ionisation threshold of $\sim$3 electrons both at a stopped pion source and at a nuclear reactor. Detectable signal rates are larger in the reactor case, but the triggered measurement and harder recoil energy spectrum afforded by the accelerator source enable lower overall background and fiducialisation of the active volume

Maternal education is associated with vaccination status of infants less than 6 months in Eastern Uganda: a cohort study

<p>Abstract</p> <p>Background</p> <p>Despite provision of free childhood vaccinations, less than half of all Ugandan infants are fully vaccinated. This study compares women with some secondary schooling to those with only primary schooling with regard to their infants' vaccination status.</p> <p>Methods</p> <p>A community-based prospective cohort study conducted between January 2006 and May 2008 in which 696 pregnant women were followed up to 24 weeks post partum. Information was collected on the mothers' education and vaccination status of the infants.</p> <p>Results</p> <p>At 24 weeks, the following vaccinations had been received: bacille Calmette-Guérin (BCG): 92%; polio-1: 91%; Diphteria-Pertussis-Tetanus-Hepatitis B-Haemophilus Influenza b (DPT-HB-Hib) 3 and polio-3: 63%. About 51% of the infants were fully vaccinated (i.e., had received all the scheduled vaccinations: BCG, polio 0, polio 1, DPT-HB-Hib1, polio 2, DPT-HB-Hib 2, polio 3 and DPT-HB-Hib 3). Only 46% of the infants whose mothers' had 5-7 years of primary education had been fully vaccinated compared to 65% of the infants whose mothers' had some secondary education. Infants whose mothers had some secondary education were less likely to miss the DPT-HB-Hib-2 vaccine (RR: 0.5, 95% CI: 0.3, 0.8), Polio-2 (RR: 0.4, 95%CI: 0.3, 0.7), polio-3 (RR: 0.5, 95%CI: 0.4, 0.7) and DPT-HB-Hib-3 (RR: 0.5, 95%CI: 0.4, 0.7). Other factors showing some association with a reduced risk of missed vaccinations were delivery at a health facility (RR = 0.8; 95%CI: 0.7, 1.0) and use of a mosquito net (RR: 0.8; 95%CI: 0.7, 1.0).</p> <p>Conclusion</p> <p>Infants whose mothers had a secondary education were at least 50% less likely to miss scheduled vaccinations compared to those whose mothers only had primary education. Strategies for childhood vaccinations should specifically target women with low formal education.</p

FGF Signaling Pathway in the Developing Chick Lung: Expression and Inhibition Studies

Background: Fibroblast growth factors (FGF) are essential key players during embryonic development. Through their specific cognate receptors (FGFR) they activate intracellular cascades, finely regulated by modulators such as Sprouty. Several FGF ligands (FGF1, 2, 7, 9, 10 and 18) signaling through the four known FGFRs, have been implicated in lung morphogenesis. Although much is known about mammalian lung, so far, the avian model has not been explored for lung studies. Methodology/Principal Findings: In this study we provide the first description of fgf10, fgfr1-4 and spry2 expression patterns in early stages of chick lung development by in situ hybridization and observe that they are expressed similarly to their mammalian counterparts. Furthermore, aiming to determine a role for FGF signaling in chick lung development, in vitro FGFR inhibition studies were performed. Lung explants treated with an FGF receptor antagonist (SU5402) presented an impairment of secondary branch formation after 48 h of culture; moreover, abnormal lung growth with a cystic appearance of secondary bronchi and reduction of the mesenchymal tissue was observed. Branching and morphometric analysis of lung explants confirmed that FGFR inhibition impaired branching morphogenesis and induced a significant reduction of the mesenchyme. Conclusions/Significance: This work demonstrates that FGFRs are essential for the epithelial-mesenchymal interactions tha

Cloning, tissue and ontogenetic expression of the taurine transporter in the flatfish Senegalese sole (Solea senegalensis)

Flatfish species seem to require dietary taurine for normal growth and development. Although dietary taurine supplementation has been recommended for flatfish, little is known about the mechanisms of taurine absorption in the digestive tract of flatfish throughout ontogeny. This study described the cloning and ontogenetic expression of the taurine transporter (TauT) in the flatfish Senegalese sole (Solea senegalensis). Results showed a high similarity between TauT in Senegalese sole and other vertebrates, but a change in TauT amino acid sequences indicates that taurine transport may differ between mammals and fish, reptiles or birds. Moreover, results showed that Senegalese sole metamorphosis is an important developmental trigger to promote taurine transport in larvae, especially in muscle tissues, which may be important for larval growth. Results also indicated that the capacity to uptake dietary taurine in the digestive tract is already established in larvae at the onset of metamorphosis. In Senegalese sole juveniles, TauT expression was highest in brain, heart and eye. These are organs where taurine is usually found in high concentrations and is believed to play important biological roles. In the digestive tract of juveniles, TauT was more expressed in stomach and hindgut, indicating that dietary taurine is quickly absorbed when digestion begins and taurine endogenously used for bile salt conjugation may be recycled at the posterior end of the digestive tract. Therefore, these results suggest an enterohepatic recycling pathway for taurine in Senegalese sole, a process that may be important for maintenance of the taurine body levels in flatfish species

The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd