Replicating adenovirus HIV/SIV recombinant priming alone or in combination with a gp140 protein boost results in significant control of viremia following a SHIV89.6P challenge in Mamu-A*01 negative rhesus macaques

Previously, replicating adenovirus type 5 host range (Ad5hr)-HIV/SIV recombinant priming in combination with SIV envelope boosting, resulted in significant, durable protection in 39% of rhesus macaques after SIVmac251 challenge. Both Env-specific antibody mediating ADCC, and cellular immunity correlated with protection. Here we evaluate the relative immunogenicities of novel HIV proteins and their contribution to protection in a SHIV89.6P model. All groups were primed with Ad-HIVenv89.6P, SIVgag239, and SIVnef239 recombinants. One group was not boosted, one received HIV89.6Pgp140DeltaCFI protein, and one a novel HIV-1 poly-peptide "peptomer". The HIV89.6Pgp140DeltaCFI protein in adjuvant strongly boosted Env-specific antibody and memory T cell responses in blood and tissue, resulting in significant reductions in acute and set point viremia. Macaques not boosted, showed a significant reduction in set point viremia, a full 32 weeks after the last Ad priming immunization. The HIV peptomer-boosted group showed a trend toward chronic viremia reduction, but was not protected.     

Clinical outcomes associated with sleep-disordered breathing in Caucasian and Hispanic children--the Tucson Children's Assessment of Sleep Apnea study (TuCASA)

STUDY OBJECTIVES: This report describes clinical outcomes and threshold levels of respiratory disturbance index (RDI) associated with sleep-disordered breathing in children participating in the Tucson Children's Assessment of Sleep Apnea study. DESIGN: A community-based, prospective cohort study designed to assess the severity of sleep-related symptoms associated with sleep-disordered breathing in children aged 6 to 11 years. SETTING: Students attending elementary school in the Tucson Unified School District. PARTICIPANTS: Unattended home polysomnograms were completed on 239 children-55.2% boys, 51% Hispanic, and 55% between the ages of 6 and 8 years. MEASUREMENTS AND RESULTS: Based on full home polysomnography, levels of RDI that correspond to a higher prevalence of clinical symptoms of sleep-disordered breathing in children aged 6 to 11 were observed. An RDI of at least 5 was associated with frequent snoring (20.3% vs 9.1%, P<.01), excessive daytime sleepiness (22.9% vs 10.7%, P<.01), and learning problems (8.5% vs 2.5%, P<.04) when no oxygen desaturation accompanied the respiratory event. An RDI of at least 1 was associated with these symptoms when a 3% oxygen desaturation was required, snoring (24.0% vs 10.4%, P<.006), excessive daytime sleepiness (24.0% vs 13.4%, P<.04), and learning problems (10.7% vs 3.0%, P<.02). Hispanic or Caucasian ethnicity, sex, age category, obesity, insomnia, and witnessed apnea were not associated with RDI regardless of event definition. CONCLUSIONS: The Tucson Children's Assessment of Sleep Apnea study has shown that there are values of RDI based on polysomnography that correspond to an increased rate of clinical symptoms in children ages 6 to 11 years.     

Phenotypic Characteristics and Diagnoses of Patients Referred to an Iron Overload Clinic

Background  

There are limited data on the phenotypic differences between patients with hereditary hemochromatosis (HH) and other forms of iron overload.     

Clinical Assessment of Scapular Positioning in Musicians: An Intertester Reliability Study

Context:

The reliability of the measurement of the distance between the posterior border of the acromion and the wall and the reliability of the modified lateral scapular slide test have not been studied. Overall, the reliability of the clinical tools used to assess scapular positioning has not been studied in musicians.

Objective:

To examine the intertester reliability of scapular observation and 2 clinical tests for the assessment of scapular positioning in musicians.

Design:

Intertester reliability study.

Setting:

University research laboratory.

Patients or Other Participants:

Thirty healthy student musicians at a single university.

Main Outcome Measure(s):

Two assessors performed a standardized observation protocol, the measurement of the distance between the posterior border of the acromion and the wall, and the modified lateral scapular slide test. Each assessor was blinded to the other''s findings.

Results:

The intertester reliability coefficients (κ) for the observation in relaxed position, during unloaded movement, and during loaded movement were 0.41, 0.63, and 0.36, respectively. The κ values for the observation of tilting and winging at rest were 0.48 and 0.42, respectively; during unloaded movement, the κ values were 0.52 and 0.78, respectively; and with a 1-kg load, the κ values were 0.24 and 0.50, respectively. The intraclass correlation coefficient (ICC) of the measurement of the acromial distance was 0.72 in relaxed position and 0.75 with the participant actively retracting both shoulders. The ICCs for the modified lateral scapular slide test varied between 0.63 and 0.58.

Conclusions:

Our results demonstrated that the modified lateral scapular slide test was not a reliable tool to assess scapular positioning in these participants. Our data indicated that scapular observation in the relaxed position and during unloaded abduction in the frontal plane was a reliable assessment tool. The reliability of the measurement of the distance between the posterior border of the acromion and the wall in healthy musicians was moderate.     

USH2A mutation analysis in 70 Dutch families with Usher syndrome type II

Usher syndrome type II (USH2) is characterised by moderate to severe high-frequency hearing impairment, progressive visual loss due to retinitis pigmentosa and intact vestibular responses. Three loci are known for USH2, however, only the gene for USH2a (USH2A) has been identified. Mutation analysis of USH2A was performed in 70 Dutch USH2 families. Ten mutations in USH2A were detected, of which three are novel, c.949C>A, c.2242C>T (p.Gln748X) and c.4405C>T (p.Gln1468X). Including 9 previously published Dutch USH2a families, estimates of the prevalence of USH2a in the Dutch USH2 population were made. Mutations were identified in 62% of the families. In 28% both mutated alleles were identified, whereas in 34% the mutation in only one allele was found. It is estimated that about 28% of the Dutch USH2 families have a different causative gene. Analysis of deduced haplotypes suggests that c.1256G>T (p.Cys419Phe) is a Dutch ancestral mutation, occurring in 16% of the alleles.     

Synthesis of Telechelic Oligomers via Atom Transfer Radical Polymerization, 1

Summary: Atom Transfer Radical Polymerization (ATRP) of styrene was carried out at 110 °C using various substituted 2‐bromoisobutyrates as initiators and the homogeneous catalyst CuBr/1,1,4,7,10,10‐hexamethyltriethylenetetramine (HMTETA). Telechelic oligomers were obtained by coupling the bromo terminated polymers using Cu(0)/PMDETA catalyst at 90 °C. The products were characterized by ¹H NMR and MALDI‐TOF and some unsaturated polymer chains were observed. They could originate from either disproportionation reaction or dehydrohalogenation of halogen terminated oligomers during MALDI analysis. Using this method, polymers with hydroxy, acid, or ester end groups were synthesized in a range of molecular weights from 1 000 to 13 000 g · mol^?1. Coupling efficiency was between 79 and 100%, depending on the structure of the initiator.

Coupling reaction of substituted polystyrenes using Cu(0)/PMDETA system at 90 °C.     

Increased chromosome instability but not cancer predisposition in haploinsufficient Bub3 mice

Mitotic spindle checkpoint proteins have been shown to play a crucial role in the accurate segregation of chromosomes during cell division. Bub3 is a member of a group of mitotic checkpoint proteins that are essential for this process. To investigate the role of Bub3 in chromosome segregation and cancer development, we analyzed haploinsufficient cells in mice. Heterozygous Bub3 embryonic fibroblasts displayed increased aneuploidy and premature sister-chromatid separation. In addition, when challenged with the microtubule disruptor nocodazole, the cells showed a slight increase in chromatid breakage and a decrease in the mitotic index. No substantial differences were observed between wild-type and Bub3 heterozygous mice in the frequency or the rate at which tumors appeared. Crossing Bub3(+/-) mice onto a heterozygous tumor-suppressor background of Trp53 or Rb1 similarly revealed no substantial differences in either the number or the rate at which tumors appeared. These results suggest that haploinsufficiency of Bub3 causes a slight increase in chromosome instability but is not clearly associated with a noticeable rise in the probability of tumor formation in the animal, possibly because of a partially functional mitotic checkpoint, or cells exhibiting chromosome instability could have activated the apoptosis pathway and thus escaped tumor induction and detection.     

Human dendritic cell responses to lipopolysaccharide and CD40 ligation are differentially regulated by interleukin-10

We evaluated the effects of interleukin (IL)-10 on the maturation of human dendritic cells (DC) induced either by lipopolysaccharide (LPS) or CD40 engagement. For this purpose, DC generated by culturing plastic-adherent peripheral blood mononuclear cells for 7 days with granulocyte/macrophage-colony-stimulating factor and IL-4 were incubated for 3 days with either LPS (10 ng/ml) or 3T6 fibroblasts transfected with the gene encoding CD40 ligand, in absence or presence of IL-10. First we found that the membrane expression of CD83, a marker of mature DC, was inhibited by IL-10 when induced by LPS but not by CD40 engagement. Likewise, IL-10 inhibited LPS-induced but not CD40-dependent CD86 (B7.2) up-regulation on DC. Furthermore, IL-10 inhibited the production of IL-8 and tumor necrosis factor-α by DC when activated by LPS but not by CD40. In contrast, IL-10 inhibited IL-12 production in both activation systems. We conclude that IL-10 differentially influences LPS-dependent and CD40-dependent pathways of DC maturation.