Transcriptional down-regulation of ccr5 in a subset of HIV+ controllers and their family members.

HIV +Elite and Viremic controllers (EC/VCs) are able to control virus infection, perhaps because of host genetic determinants. We identified 16% (21 of 131) EC/VCs with CD4 +T cells with resistance specific to R5-tropic HIV, reversed after introduction of ccr5. R5 resistance was not observed in macrophages and depended upon the method of T cell activation. CD4 +T cells of these EC/VCs had lower ccr2 and ccr5 RNA levels, reduced CCR2 and CCR5 cell-surface expression, and decreased levels of secreted chemokines. T cells had no changes in chemokine receptor mRNA half-life but instead had lower levels of active transcription of ccr2 and ccr5, despite having more accessible chromatin by ATAC-seq. Other nearby genes were also down-regulated, over a region of ~500 kb on chromosome 3p21. This same R5 resistance phenotype was observed in family members of an index VC, also associated with ccr2/ccr5 down-regulation, suggesting that the phenotype is heritable

A comparison of HAART outcomes between the US military HIV Natural History Study (NHS) and HIV Atlanta Veterans Affairs Cohort Study (HAVACS).

INTRODUCTION: The Department of Defense (DoD) and the Department of Veterans Affairs (VA) provide comprehensive HIV treatment and care to their beneficiaries with open access and few costs to the patient. Individuals who receive HIV care in the VA have higher rates of substance abuse, homelessness and unemployment than individuals who receive HIV care in the DoD. A comparison between individuals receiving HIV treatment and care from the DoD and the VA provides an opportunity to explore the impact of individual-level characteristics on clinical outcomes within two healthcare systems that are optimized for clinic retention and medication adherence. METHODS: Data were collected on 1065 patients from the HIV Atlanta VA Cohort Study (HAVACS) and 1199 patients from the US Military HIV Natural History Study (NHS). Patients were eligible if they had an HIV diagnosis and began HAART between January 1, 1996 and June 30, 2010. The analysis examined the survival from HAART initiation to all-cause mortality or an AIDS event. RESULTS: Although there was substantial between-cohort heterogeneity and the 12-year survival of participants in NHS was significantly higher than in HAVACS in crude analyses, this survival disparity was reduced from 21.5% to 1.6% (mortality only) and 26.8% to 4.1% (combined mortality or AIDS) when controlling for clinical and demographic variables. CONCLUSION: We assessed the clinical outcomes for individuals with HIV from two very similar government-sponsored healthcare systems that reduced or eliminated many barriers associated with accessing treatment and care. After controlling for clinical and demographic variables, both 12-year survival and AIDS-free survival rates were similar for the two study cohorts who have open access to care and medication despite dramatic differences in socioeconomic and behavioral characteristics

Construction and validation of an developmental profile assessment tool for children with autistic spectrum disorder

Nos últimos anos a investigação tem dado particular relevância às alterações do Processamento Sensorial nas crianças com perturbações do espectro do autismo (PEA) e a literatura refere que entre 42% a 88% das crianças com PEA apresentam este tipo de disfunção. Nesta linha foi definido um projeto de investigação centrado na construção de uma escala que avalie a tradicional tríade que caracteriza as crianças com PEA (Interação, Comunicação e Comportamento e interesses repetitivos e estereotipados), enriquecida pela inclusão de um novo domínio: o Processamento Sensorial. Com a construção e validação desta escala pretendemos que pais e profissionais utilizem colaborativamente um instrumento de avaliação da intervenção que lhes permita monitorizar o processo de apoio e adequar as suas práticas. Neste artigo descrevemos os procedimentos e os resultados das sucessivas fases de construção do instrumento, desde as análises iniciais mais qualitativas até aos estudos centrados na análise quantitativa dos itens.During the last few years, research has focused on changes in Sensory Processing in children with Autistic Spectrum Disorder (ASD). As a result, literature has shown that between 42% and 88% of children with ASD present this type of disorder. Based on these findings, a research project was designed centring on the construction of a tool to assess the traditional triad that characterizes children with ASD (Interaction, Communication and Behaviour and Repetitive and Stereotyped Interests), to which was added a new domain: Sensory Processing. By constructing and validating this assessment tool, the intention is for parents and professionals to collaboratively apply this intervention assessment instrument in order to monitor the support process and adapt their practices. In this paper, we describe procedures and results of the successive stages entailed in constructing this instrument, from the first primarily qualitative analyses up to the studies centred on the quantitative item analysis.Fundação para a Ciência e Tecnologia (FCT)ABPEE - Associação Brasileira de Pesquisadores em Educação EspecialConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CAPESMinistério da Educação - BrasilMinistério da Ciência e da Tecnologia - BrasilGoverno Federal - Brasi

Prospective Study of Infection, Colonization and Carriage of Methicillin-Resistant Staphylococcus Aureus in an Outbreak Affecting 990 Patients

In the three years between November 1989 and October 1992, an outbreak of methicillin-resistantStaphylococcus aureus (MRSA) affected 990 patients at a university hospital. The distribution of patients with carriage, colonization or infection was investigated prospectively. Nosocomial acquisition was confirmed in at least 928 patients, 525 of whom were identified from clinical specimens as being infected (n=418) or colonized (n=107) by MRSA. An additional 403 patients were identified from screening specimens, of whom 58 subsequently became infected and 18 colonized. Screening of the nose, throat and perineum detected 98 % of all carriers. Of the 580 infections in 476 patients, surgical wound, urinary tract and skin infections accounted for 58 % of the infections. Of the 476 infected patients, death was attributable to MRSA infection in 13 %. Colonization with MRSA was found in 127 patients and 42 % of 165 colonized sites were the skin. Auto-infection from nasal carriage or cross-infection, probably via staff hands, seemed to be the most common mode of acquisition of MRSA infections

Intestinal carriage of Staphylococcus aureus: How does its frequency compare with that of nasal carriage and what is its clinical impact?

The bacterial species Staphylococcus aureus, including its methicillin-resistant variant (MRSA), finds its primary ecological niche in the human nose, but is also able to colonize the intestines and the perineal region. Intestinal carriage has not been widely investigated despite its potential clinical impact. This review summarizes literature on the topic and sketches the current state of affairs from a microbiological and infectious diseases' perspective. Major findings are that the average reported detection rate of intestinal carriage in healthy individuals and patients is 20% for S. aureus and 9% for MRSA, which is approximately half of that for nasal carriage. Nasal carriage seems to predispose to intestinal carriage, but sole intestinal carriage occurs relatively frequently and is observed in 1 out of 3 intestinal carriers, which provides a rationale to include intestinal screening for surveillance or in outbreak settings. Colonization of the intestinal tract with S. aureus at a young age occurs at a high frequency and may affect the host's immune system. The frequency of intestinal carriage is generally underestimated and may significantly contribute to bacterial dissemination and subsequent risk of infections. Whether intestinal rather than nasal S. aureus carriage is a primary predictor for infections is still ill-defined

The economic impact of moderate stage Alzheimer's disease in Italy: Evidence from the UP-TECH randomized trial

Background: There is consensus that dementia is the most burdensome disease for modern societies. Few cost-of-illness studies examined the complexity of Alzheimer's disease (AD) burden, considering at the same time health and social care, cash allowances, informal care, and out-of-pocket expenditure by families. Methods: This is a comprehensive cost-of-illness study based on the baseline data from a randomized controlled trial (UP-TECH) enrolling 438 patients with moderate AD and their primary caregiver living in the community. Results: The societal burden of AD, composed of public, patient, and informal care costs, was about �20,000/yr. Out of this, the cost borne by the public sector was �4,534/yr. The main driver of public cost was the national cash-for-care allowance (�2,324/yr), followed by drug prescriptions (�1,402/yr). Out-of-pocket expenditure predominantly concerned the cost of private care workers. The value of informal care peaked at �13,590/yr. Socioeconomic factors do not influence AD public cost, but do affect the level of out-of-pocket expenditure. Conclusion: The burden of AD reflects the structure of Italian welfare. The families predominantly manage AD patients. The public expenditure is mostly for drugs and cash-for-care benefits. From a State perspective in the short term, the advantage of these care arrangements is clear, compared to the cost of residential care. However, if caregivers are not adequately supported, savings may be soon offset by higher risk of caregiver morbidity and mortality produced by high burden and stress. The study has been registered on the website www.clinicaltrials.org (Trial Registration number: NCT01700556). Copyright � International Psychogeriatric Association 2015

Cost-Effectiveness of HIV Screening in STD Clinics, Emergency Departments, and Inpatient Units: A Model-Based Analysis

Identifying and treating persons with human immunodeficiency virus (HIV) infection early in their disease stage is considered an effective means of reducing the impact of the disease. We compared the cost-effectiveness of HIV screening in three settings, sexually transmitted disease (STD) clinics serving men who have sex with men, hospital emergency departments (EDs), settings where patients are likely to be diagnosed early, and inpatient diagnosis based on clinical manifestations.We developed the Progression and Transmission of HIV/AIDS model, a health state transition model that tracks index patients and their infected partners from HIV infection to death. We used program characteristics for each setting to compare the incremental cost per quality-adjusted life year gained from early versus late diagnosis and treatment. We ran the model for 10,000 index patients for each setting, examining alternative scenarios, excluding and including transmission to partners, and assuming HAART was initiated at a CD4 count of either 350 or 500 cells/µL. Screening in STD clinics and EDs was cost-effective compared with diagnosing inpatients, even when including only the benefits to the index patients. Screening patients in STD clinics, who have less-advanced disease, was cost-effective compared with ED screening when treatment with HAART was initiated at a CD4 count of 500 cells/µL. When the benefits of reduced transmission to partners from early diagnosis were included, screening in settings with less-advanced disease stages was cost-saving compared with screening later in the course of infection. The study was limited by a small number of observations on CD4 count at diagnosis and by including transmission only to first generation partners of the index patients.HIV prevention efforts can be advanced by screening in settings where patients present with less-advanced stages of HIV infection and by initiating treatment with HAART earlier in the course of infection

Dual-energy X-ray absorptiometry and calculated FRAX risk scores may underestimate osteoporotic fracture risk in Vitamin D-deficient veterans with HIV infection

Objective: We evaluated the utility of the Fracture Risk Assessment Tool (FRAX) in assessing fracture risk in patients with human immunodeficiency virus (HIV) and vitamin D deficiency. Methods: This was a retrospective study of HIV-infected patients with co-existing vitamin D deficiency at the Atlanta Veterans Affairs Medical Center. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry (DEXA), and the 10-year fracture risk was calculated by the FRAX algorithm. Two independent radiologists reviewed lateral chest radiographs for the presence of subclinical vertebral fractures. Results: We identified 232 patients with HIV and vitamin D deficiency. Overall, 15.5% of patients met diagnostic criteria for osteoporosis on DEXA, and 58% had low BMD (T-score between −1 and −2.5). The median risk of any major osteoporotic and hip fracture by FRAX score was 1.45 and 0.10%, respectively. Subclinical vertebral fractures were detected in 46.6% of patients. Compared to those without fractures, those with fractures had similar prevalence of osteoporosis (15.3% versus 15.7%; P>.999), low BMD (53.2% versus 59.3%; P = .419), and similar FRAX hip scores (0.10% versus 0.10%; P = .412). While the FRAX major score was lower in the nonfracture group versus fracture group (1.30% versus 1.60%; P = .025), this was not clinically significant. Conclusion: We found a high prevalence of subclinical vertebral fractures among vitamin D–deficient HIV patients; however, DEXA and FRAX failed to predict those with fractures. Our results suggest that traditional screening tools for fragility fractures may not be applicable to this high-risk patient population

Melody and pitch processing in five musical savants with congenital blindness

Abstract. We examined absolute-pitch (AP) and short-term musical memory abilities of five musical savants with congenital blindness, seven musicians, and seven non-musicians with good vision and normal intelligence in two experiments. In the first, short-term memory for musical phrases was tested and the savants and musicians performed statistically indistinguishably, both signifi- cantly outperforming the non-musicians and remembering more material from the C major scale sequences than random trials. In the second experiment, participants learnt associations between four pitches and four objects using a non-verbal paradigm. This experiment approximates to testing AP ability. Low statistical power meant the savants were not statistically better than the musicians, although only the savants scored statistically higher than the non-musicians. The results are evidence for a musical module, separate from general intelligence; they also support the anecdotal reporting of AP in musical savants, which is thought to be necessary for the development of musical-savant skill