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

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

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

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

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

Embolic stroke complicating Staphylococcus aureus endocarditis circumstantially linked to rectal trauma from foreign body: a first case report

BACKGROUND: Diagnostic and therapeutic instrumentation of the lower gastrointestinal tract has been reported to result in bacteremia and endocarditis. No such case has been reported in persons with a history of rectal foreign body insertion despite its potential for greater trauma. CASE PRESENTATION: A 58-year-old male was admitted with confusion and inability to speak. His past history was notable for hospitalization to extract a retained plastic soda bottle from the rectosigmoid two years prior. On examination, he was febrile, tachycardic and hypotensive. There was an apical pansystolic murmur on cardiac examination. He had a mixed receptive and expressive aphasia, and a right hemiparesis. On rectal examination he had perianal erythema and diminished sphincter tone. Magnetic resonance imaging of the brain showed infarction of the occipital and frontal lobes. Transesophageal Echocardiography of the heart revealed vegetations on the mitral valve. All of his blood culture bottles grew methicillin sensitive Staphylococcus aureus. He was successfully treated for bacterial endocarditis with intravenous nafcillin and gentamicin. The rectum is frequently colonized by Staphylococcus aureus and trauma to its mucosa can lead to bacteremia and endocarditis with this organism. In the absence of corroborative evidence such as presented here, it is difficult to make a correlation between staphylococcal endocarditis and anorectal foreign body insertion due to patients being less than forthcoming CONCLUSION: There is a potential risk of staphylococcal bacteremia and endocarditis with rectal foreign body insertion. Further studies are needed to explore this finding. Detailed sexual history and patient counseling should be made a part of routine primary care

Local and global processing in savant artists with autism

Abstract. We explored the hypothesis that an enhanced local processing style is characteristic of both art and autism spectrum disorder (ASD) by examining local and global processing in savant artists with ASD. Specifically, savant artists were compared against non-talented individuals with ASD or mild/moderate learning difficulties (MLD), as well as artistically talented or non- talented students, on the block-design task and meaningful and abstract versions of the embedded figures test (EFT). Results demonstrated that there were no significant differences between the meaningful and abstract versions of the EFT, in any of the groups. This suggests that the primary process governing performance on this task was perceptual (local), rather than conceptual (global). More interestingly, the savant artists performed above the level of the ASD and MLD groups on the block-design test, but not the EFT. Despite both the block-design task and the EFT measuring local processing abilities, we suggest that this result is due to the block-design task being an active construction task (requiring the conversion of a visual input into a motor output), whereas the EFT is a passive recognition task. Therefore, although an enhanced local processing style is an important aspect of savant artistic talent, motor control also appears to be a necessary skill

Genetic variation in Pneumocystis carinii isolates from different geographic regions: implications for transmission.

To study transmission patterns of Pneumocystis carinii pneumonia (PCP) in persons with AIDS, we evaluated P. carinii isolates from patients in five U.S. cities for variation at two independent genetic loci, the mitochondrial large subunit rRNA and dihydropteroate synthase. Fourteen unique multilocus genotypes were observed in 191 isolates that were examined at both loci. Mixed infections, accounting for 17.8% of cases, were associated with primary PCP. Genotype frequency distribution patterns varied by patients' place of diagnosis but not by place of birth. Genetic variation at the two loci suggests three probable characteristics of transmission: that most cases of PCP do not result from infections acquired early in life, that infections are actively acquired from a relatively common source (humans or the environment), and that humans, while not necessarily involved in direct infection of other humans, are nevertheless important in the transmission cycle of P. carinii f. sp. hominis

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