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

Explaining and inducing savant skills: privileged access to lower level, less-processed information

I argue that savant skills are latent in us all. My hypothesis is that savants have privileged access to lower level, less-processed information, before it is packaged into holistic concepts and meaningful labels. Owing to a failure in top-down inhibition, they can tap into information that exists in all of our brains, but is normally beyond conscious awareness. This suggests why savant skills might arise spontaneously in otherwise normal people, and why such skills might be artificially induced by low-frequency repetitive transcranial magnetic stimulation. It also suggests why autistic savants are atypically literal with a tendency to concentrate more on the parts than on the whole and why this offers advantages for particular classes of problem solving, such as those that necessitate breaking cognitive mindsets. A strategy of building from the parts to the whole could form the basis for the so-called autistic genius. Unlike the healthy mind, which has inbuilt expectations of the world (internal order), the autistic mind must simplify the world by adopting strict routines (external order)

Creativity in savant artists with autism

Background: Individuals with autism spectrum disorder (ASD) often display impairments in creativity, yet savant artists with ASD can produce highly novel and original artistic outputs. To date, there have been no systematic attempts to explore creativity in savant artists with ASD. Methods: Nine savant artists with ASD were compared with nine talented artists, nine non-artistically talented individuals with ASD, and nine individuals with moderate learning difficulties (MLD), on tasks in and out of their domain of expertise. This was to ascertain whether the performance of the savant artists was related to their artistic ability, their diagnosis of ASD or their level of intellectual functioning. Results: On a drawing task (the Torrance Test of Creative Thinking; Torrance, 1974), the responses of the art students were more creative (scoring higher on measures of fluency, originality, elaboration and flexibility) than the savant, ASD and MLD groups. However, the savants did produce more elaborative responses than the ASD and MLD groups. On a non-drawing construction task (figural synthesis; Finke & Slayton, 1988), the savants produced more original outputs than the ASD and MLD groups (scoring similarly to the art students). No group differences were found regarding fluency on this task. Conclusions: On standardised creativity tasks, savant artists with ASD display high levels of elaboration (on drawing tasks) and originality (on non-drawing construction tasks), relative to groups with ASD or MLD. High elaboration and originality may result from a local processing bias, coupled with artistic talent, in this group

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

Cancer incidence in HIV-infected versus uninfected veterans: Comparison of cancer registry and ICD-9 code diagnoses

Background: Given the growing interest in the cancer burden in persons living with HIV/AIDS, we examined the validity of data sources for cancer diagnoses (cancer registry versus International Classification of Diseases, Ninth Revision [ICD-9 codes]) and compared the association between HIV status and cancer risk using each data source in the Veterans Aging Cohort Study (VACS), a prospective cohort of HIV-infected and uninfected veterans from 1996 to 2008. Methods: We reviewed charts to confirm potential incident cancers at four VACS sites. In the entire cohort, we calculated cancer-type-specific age-, sex-, race/ethnicity-, and calendar-period-standardized incidence rates and incidence rate ratios (IRR) (HIV-infected versus uninfected). We calculated standardized incidence ratios (SIR) to compare VACS and Surveillance, Epidemiology, and End Results rates. Results: Compared to chart review, both Veterans Affairs Central Cancer Registry (VACCR) and ICD-9 diagnoses had approximately 90% sensitivity; however, VACCR had higher positive predictive value (96% versus 63%). There were 6,010 VACCR and 13,386 ICD-9 incident cancers among 116,072 veterans. Although ICD-9 rates tended to be double VACCR rates, most IRRs were in the same direction and of similar magnitude, regardless of data source. Using source, all cancers combined, most viral-infection-related cancers, lung cancer, melanoma, and leukemia had significantly elevated IRRs. Using ICD-9, eight additional IRRs were significantly elevated, most likely due to false positive diagnoses. Most ICD-9 SIRs were significantly elevated and all were higher than the corresponding VACCR SIR. Conclusions: ICD-9 may be used with caution for estimating IRRs, but should be avoided when estimating incidence or SIRs. Elevated cancer risk based on VACCR diagnoses among HIV-infected veterans was consistent with other studies

Sulfa or Sulfone Prophylaxis and Geographic Region Predict Mutations in the Pneumocystis carinii Dihydropteroate Synthase Gene

To determine factors associated with mutations in the Pneumocystis carinii dihydropteroate synthase (DHPS) gene, a prospective study of human immunodeficiency virus (HIV)-infected patients with confirmed P. carinii pneumonia was conducted in Atlanta, Seattle, and San Francisco. Clinical information was obtained from patient interview and chart abstraction. DHPS genotype was determined from DNA sequencing. Overall, 76 (68.5%) of 111 patients had a mutant DHPS genotype, including 22 (81.5%) of 27 patients from San Francisco. In multivariate analysis, sulfa or sulfone prophylaxis and study site were independent predictors of a mutant genotype. Fourteen (53.8%) of 26 patients who were newly diagnosed with HIV infection and had never taken prophylaxis had a mutant genotype. The significance of geographic location as a risk factor for mutant genotype and the high proportion of mutant genotypes among persons never prescribed prophylaxis, including those newly diagnosed with HIV infection, provide indirect evidence that these mutations are transmitted from person to person either directly or through a common environmental source

A systematic review of physiological reactivity to stimuli in autism

Objective: The prevalence of abnormal behavioural responses to a variety of stimuli among individuals with autism has led researchers to examine whether physiological reactivity is typical in this population. The current paper reviewed studies assessing physiological reactivity to sensory, social and emotional, and stressor stimuli in individuals with autism. Methods: Systematic searches of electronic databases identified 57 studies that met our inclusion criteria. A novel measure of methodological quality suitable for use with non-randomised, non-interventional, psychophysiological studies was also developed and applied. Results: Individuals with autism were found to respond differently than typically developing controls in 78.6%, 66.7%, and 71.4% of sensory, social and emotional, and stressor stimulus classes, respectively. Conclusions: Individual differences in physiological reactivity are clearly present in autism, suggesting additional research is needed to determine the variables relating to physiological reactivity among those with ASD and to examine the possibility of physiological subtype responders in this population

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

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