HIV Testing and Conspiracy Beliefs Regarding the Origins of HIV among African Americans

Abstract Conspiracy beliefs regarding the origins of HIV are common among African Americans, and have been associated with engaging in HIV risk behaviors but also with earlier diagnosis among HIV patients. The objective of the present study was to test the association of HIV serostatus testing with conspiracy beliefs. A total of 1430 African Americans from low-income neighborhoods with high rates of drug use were surveyed in 1997-1999 in face-to-face interviews. Two 4-point items assessed if participants agreed that AIDS was started by an experiment that went wrong and AIDS was created to kill blacks and poor folks. A binary variable indicated if the respondent agreed with the statements, on average. 22.5% of the sample endorsed conspiracy beliefs, 4.0% of whom reported not having had an HIV test, compared to 7.7% of those who did not endorse conspiracy beliefs. In multivariable logistic regression modeling, never having had an HIV test was significantly associated with conspiracy beliefs (adjusted odds ratio [AOR]=0.43, 95% confidence interval [CI]=1.3-4.3), having a high school education (AOR=0.55, CI=0.35-0.84), having depression (AOR=1.61, CI=1.02-2.52), female gender (AOR=0.54, CI=0.34-0.86), younger age, and a history of injection drug use (AOR=0.36, CI=0.23-0.56), but not sex risk behaviors (multiple partners, irregular condom use). The finding that individuals who have conspiracy beliefs are more likely to have been tested for HIV may partially explain why HIV-positive individuals who endorse conspiracy beliefs are more likely to obtain an earlier diagnosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78123/1/apc.2009.0061.pd

Blunt cerebrovascular trauma causing vertebral arteryd issection in combination with a laryngeal fracture: a case report

<p>Abstract</p> <p>Introduction</p> <p>The diagnosis and therapy of blunt cerebrovascular injuries has become a focus since improved imaging technology allows adequate description of the injury. Although it represents a rare injury the long-term complications can be fatal but mostly prevented by adequate treatment.</p> <p>Case presentation</p> <p>A 33-year-old Caucasian man fell down a 7-meter scarp after losing control of his quad bike in a remote area. Since endotracheal intubation was unsuccessfully attempted due to the severe cervical swelling as well as oral bleeding an emergency tracheotomy was performed on scene. He was hemodynamically unstable despite fluid resuscitation and intravenous therapy with vasopressors and was transported by a helicopter to our trauma center. He had a stable fracture of the arch of the seventh cervical vertebra and fractures of the transverse processes of C5-C7 with involvement of the lateral wall of the transverse foramen. An abort of the left vertebral artery signal at the first thoracic vertebrae with massive hemorrhage as well as a laryngeal fracture was also detected. Further imaging showed retrograde filling of the left vertebral artery at C5 distal of the described abort. After stabilization and reconfirmation of intracranial perfusion during the clinical course weaning was started. At the time of discharge, he was aware and was able to move all extremities.</p> <p>Conclusion</p> <p>We report a rare case of a patient with vertebral artery dissection in combination with a laryngeal fracture after blunt trauma. Thorough diagnostic and frequent reassessments are recommended. Most patients can be managed with conservative treatment.</p

A systematic review of biomarkers for disease progression in Parkinson's disease

Peer reviewedPublisher PD

A Triple Protostar System Formed via Fragmentation of a Gravitationally Unstable Disk

Binary and multiple star systems are a frequent outcome of the star formation process, and as a result, almost half of all sun-like stars have at least one companion star. Theoretical studies indicate that there are two main pathways that can operate concurrently to form binary/multiple star systems: large scale fragmentation of turbulent gas cores and filaments or smaller scale fragmentation of a massive protostellar disk due to gravitational instability. Observational evidence for turbulent fragmentation on scales of $>$1000~AU has recently emerged. Previous evidence for disk fragmentation was limited to inferences based on the separations of more-evolved pre-main sequence and protostellar multiple systems. The triple protostar system L1448 IRS3B is an ideal candidate to search for evidence of disk fragmentation. L1448 IRS3B is in an early phase of the star formation process, likely less than 150,000 years in age, and all protostars in the system are separated by $<$200~AU. Here we report observations of dust and molecular gas emission that reveal a disk with spiral structure surrounding the three protostars. Two protostars near the center of the disk are separated by 61 AU, and a tertiary protostar is coincident with a spiral arm in the outer disk at a 183 AU separation. The inferred mass of the central pair of protostellar objects is $\sim$1 M$_{sun}$, while the disk surrounding the three protostars has a total mass of $\sim$0.30 M_{\sun}. The tertiary protostar itself has a minimum mass of $\sim$0.085 M$_{sun}$. We demonstrate that the disk around L1448 IRS3B appears susceptible to disk fragmentation at radii between 150~AU and 320~AU, overlapping with the location of the tertiary protostar. This is consistent with models for a protostellar disk that has recently undergone gravitational instability, spawning one or two companion stars.Comment: Published in Nature on Oct. 27th. 24 pages, 8 figure

Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B

Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells. Application of PKA inhibitors, KT5720 or H89, caused a significant inhibition of Kv currents. Tonic PKA-mediated activation of Kv appears maximal as application of isoprenaline (a β-adrenoceptor agonist) or dibutyryl-cAMP failed to enhance Kv currents. We also show that this modulation of Kv by PKA can be reversed by protein phosphatase 2B/calcineurin (PP2B). PKA-dependent inhibition of Kv by KT5720 can be abrogated by pre-treatment with the PP2B inhibitor cyclosporin A, or inclusion of a PP2B auto-inhibitory peptide in the pipette solution. Finally, we demonstrate that tonic PKA-mediated modulation of Kv requires intact caveolae. Pre-treatment of the cells with methyl-β-cyclodextrin to deplete cellular cholesterol, or adding caveolin-scaffolding domain peptide to the pipette solution to disrupt caveolae-dependent signalling each attenuated PKA-mediated modulation of the Kv current. These findings highlight a novel, caveolae-dependent, tonic modulatory role of PKA on Kv channels providing new insight into mechanisms and the potential for pharmacological manipulation of vascular tone

Caloric Restriction Alters the Metabolic Response to a Mixed-Meal: Results from a Randomized, Controlled Trial

OBJECTIVES: To determine if caloric restriction (CR) would cause changes in plasma metabolic intermediates in response to a mixed meal, suggestive of changes in the capacity to adapt fuel oxidation to fuel availability or metabolic flexibility, and to determine how any such changes relate to insulin sensitivity (S(I)). METHODS: Forty-six volunteers were randomized to a weight maintenance diet (Control), 25% CR, or 12.5% CR plus 12.5% energy deficit from structured aerobic exercise (CR+EX), or a liquid calorie diet (890 kcal/d until 15% reduction in body weight)for six months. Fasting and postprandial plasma samples were obtained at baseline, three, and six months. A targeted mass spectrometry-based platform was used to measure concentrations of individual free fatty acids (FFA), amino acids (AA), and acylcarnitines (AC). S(I) was measured with an intravenous glucose tolerance test. RESULTS: Over three and six months, there were significantly larger differences in fasting-to-postprandial (FPP) concentrations of medium and long chain AC (byproducts of FA oxidation) in the CR relative to Control and a tendency for the same in CR+EX (CR-3 month P = 0.02; CR-6 month P = 0.002; CR+EX-3 month P = 0.09; CR+EX-6 month P = 0.08). After three months of CR, there was a trend towards a larger difference in FPP FFA concentrations (P = 0.07; CR-3 month P = 0.08). Time-varying differences in FPP concentrations of AC and AA were independently related to time-varying S(I) (P<0.05 for both). CONCLUSIONS: Based on changes in intermediates of FA oxidation following a food challenge, CR imparted improvements in metabolic flexibility that correlated with improvements in S(I). TRIAL REGISTRATION: ClinicalTrials.gov NCT00099151

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P &lt; 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms

Feed-Forward Microprocessing and Splicing Activities at a MicroRNA–Containing Intron

The majority of mammalian microRNA (miRNA) genes reside within introns of protein-encoding and non-coding genes, yet the mechanisms coordinating primary transcript processing into both mature miRNA and spliced mRNA are poorly understood. Analysis of melanoma invasion suppressor miR-211 expressed from intron 6 of melastatin revealed that microprocessing of miR-211 promotes splicing of the exon 6–exon 7 junction of melastatin by a mechanism requiring the RNase III activity of Drosha. Additionally, mutations in the 5′ splice site (5′SS), but not in the 3′SS, branch point, or polypyrimidine tract of intron 6 reduced miR-211 biogenesis and Drosha recruitment to intron 6, indicating that 5′SS recognition by the spliceosome promotes microprocessing of miR-211. Globally, knockdown of U1 splicing factors reduced intronic miRNA expression. Our data demonstrate novel mutually-cooperative microprocessing and splicing activities at an intronic miRNA locus and suggest that the initiation of spliceosome assembly may promote microprocessing of intronic miRNAs

Magnetic resonance imaging of the erector spinae muscles in Duchenne muscular dystrophy: implication for scoliotic deformities

<p>Abstract</p> <p>Background</p> <p>In Duchenne muscular dystrophy (DMD), the muscular degeneration often leads to the development of scoliosis. Our objective was to investigate how anatomical changes in back muscles can lead to scoliosis. Muscular volume and the level of fat infiltration in those muscles were thus evaluated, in non-scoliotic, pre-scoliotic and scoliotic patients. The overlying skin thickness over the apex level of scoliotic deformations was also measured to facilitate the interpretation of electromyographic signals when recorded on the skin surface.</p> <p>Methods</p> <p>In 8 DMD patients and two healthy controls with no known muscular deficiencies, magnetic resonance imaging (MRI) was used to measure continuously at 3 mm intervals the distribution of the erector spinae (ES) muscle in the T8-L4 region as well as fat infiltration in the muscle and overlying skin thickness: four patients were non-scoliotic (NS), two were pre-scoliotic (PS, Cobb angle < 15°) and two were scoliotic (S, Cobb angle ≥ 15°). For each subject, 63 images 3 mm thick of the ES muscle were obtained in the T8-L4 region on both sides of the spine. The pixel dimension was 0.39 × 0.39 mm. With a commercial software, on each 12 bits image, the ES contour on the left and on the right sides of the spine were manually determined as well as those of its constituents i.e., the iliocostalis (IL), the longissimus (LO) and the spinalis (SP) muscles. Following this segmentation, the surfaces within the contours were determined, the muscles volume were obtained, the amount of fat infiltration inside each muscle was evaluated and the overlying skin thickness measured.</p> <p>Findings</p> <p>The volume of the ES muscle of our S and PS patients was found smaller on the convex side relative to the concave one by 5.3 ± 0.7% and 2.8 ± 0.2% respectively. For the 4 NS patients, the volume difference of this muscle between right and left sides was 2.1 ± 1.5% and for the 2 controls, it was 1.4 ± 1.2%. Fat infiltration for the S and the PS patients was larger on the convex side than on the concave one (4.4 ± 1.6% and 4.5 ± 0.7% respectively) and the difference was more important near the apex. Infiltration was more important in the lateral IL muscle than in the medial SP and it was always larger near L2 than at any other spinal level. Fat infiltration was much more important in the ES for the DMD patients (49.9% ± 1.6%) than for the two controls (2.6 ± 0.8%). As for the overlying skin thickness measured near the deformity of the patients, it was larger on the concave than on the convex side: 14.8 ± 6.1 vs 13.5 ± 5.7 mm for the S and 10.3 ± 6.3 vs 9.8 ± 5.6 mm for the PS.</p> <p>Interpretation</p> <p>In DMD patients, our results indicate that a larger replacement of muscles fibers by fat infiltration on one side of the spine is a factor that can lead to the development of scoliosis. Efforts to slow such an infiltration on the most affected side of the spine could thus be beneficial to those patients by delaying the apparition of the scoliotic deformation. In addition to anatomical considerations, results obtained from the same patients but in experiments dealing with electromyography recordings, point to differences in the muscular contraction mechanisms and/or of the neural input to back muscles. This is similar to the adolescent idiopathic scoliosis (AIS) where a role of the nervous system in the development of the deformation has also been suggested.</p

The Procedural Index for Mortality Risk (PIMR): an index calculated using administrative data to quantify the independent influence of procedures on risk of hospital death

<p>Abstract</p> <p>Background</p> <p>Surgeries and other procedures can influence the risk of death in hospital. All published scales that predict post-operative death risk require clinical data and cannot be measured using administrative data alone. This study derived and internally validated an index that can be calculated using administrative data to quantify the independent risk of hospital death after a procedure.</p> <p>Methods</p> <p>For all patients admitted to a single academic centre between 2004 and 2009, we estimated the risk of all-cause death using the Kaiser Permanente Inpatient Risk Adjustment Methodology (KP-IRAM). We determined whether each patient underwent one of 503 commonly performed therapeutic procedures using Canadian Classification of Interventions codes and whether each procedure was emergent or elective. Multivariate logistic regression modeling was used to measure the association of each procedure-urgency combination with death in hospital independent of the KP-IRAM risk of death. The final model was modified into a scoring system to quantify the independent influence each procedure had on the risk of death in hospital.</p> <p>Results</p> <p>275 460 hospitalizations were included (137,730 derivation, 137,730 validation). In the derivation group, the median expected risk of death was 0.1% (IQR 0.01%-1.4%) with 4013 (2.9%) dying during the hospitalization. 56 distinct procedure-urgency combinations entered our final model resulting in a Procedural Index for Mortality Rating (PIMR) score values ranging from -7 to +11. In the validation group, the PIMR score significantly predicted the risk of death by itself (c-statistic 67.3%, 95% CI 66.6-68.0%) and when added to the KP-IRAM model (c-index improved significantly from 0.929 to 0.938).</p> <p>Conclusions</p> <p>We derived and internally validated an index that uses administrative data to quantify the independent association of a broad range of therapeutic procedures with risk of death in hospital. This scale will improve risk adjustment when administrative data are used for analyses.</p