Modulation masking release using the Brazilian-Portuguese HINT: Psychometric functions and the effect of speech time compression

Objective: The Brazilian-Portuguese hearing in noise test (HINT) was used to investigate the benefit to speech recognition of listening in a fluctuating background. The goal was to determine whether modulation masking release varied as a function of the speech-to-masker ratio at threshold. Speech-to-masker ratio at threshold was manipulated using the novel approach of adjusting the time-compression of the speech. Design: Experiment 1 measured performance-intensity functions in both a steady speech-shaped noise masker and a 10-Hz square-wave modulated masker. Experiment 2 measured speech-to-masker ratios at threshold as a function of time-compression of the speech (0, 33, and 50%) in both maskers. Study sample: Participants were normal-hearing adults who were native speakers of Brazilian Portuguese (Experiment 1: N = 10; Experiment 2: N = 30). Results: The slope of the performance-intensity function was shallower in the modulated masker than in the steady masker for both words and sentences. Thresholds increased with increasing time-compression in both maskers, but more markedly in the modulated masker, resulting in reduced modulation masking release with increasing time-compression. Conclusions: Speech-to-masker ratio at threshold varies with time-compression of speech. The results are relevant to the issue of whether degree of masker modulation benefit depends on speech-to-masker ratio at threshold.     

In vitro TNF blockade enhances ex vivo expansion of regulatory T cells in patients with immune thrombocytopenia

Tumour necrosis factor‐α (TNF) is an inflammatory cytokine that is elevated in a number of autoimmune diseases including immune thrombocytopenia (ITP), a bleeding disorder characterized by low platelet counts. In vitro TNF blockade increases expansion of the regulatory T cell (Treg) IKZF2 (also termed Helios) subset in T cell‐monocyte cocultures from healthy donors, but its role on proliferative responses of Tregs in ITP patients, who have altered immunoregulatory compartment, remains unclear. TNF in CD4+ T cells from patients with chronic ITP were elevated and negatively correlated with peripheral Treg frequencies, suggesting a possible inhibitory effect of TNF on ITP Tregs. In vitro antibody neutralization with anti‐TNF in T cell‐monocyte cocultures resulted in a robust expansion of pre‐existing ITP Tregs, higher than in healthy controls. Similar to the effects of anti‐TNF antibodies, TNF blockade with antibodies against TNFRSF1B (anti‐TNFRSF1B, previously termed anti‐TNFRII) almost doubled ITP Treg expansion whereas neutralization with anti‐TNFRSF1A (anti‐TNFRI) antibodies had no effect on proliferative responses of Tregs. In addition, TNFRSF1B levels on ITP Tregs were significantly elevated, which may explain the increased susceptibility of patient Tregs to the actions of TNF blockade. Altogether, these data raise the possibility that TNF blockers, through their ability to increase Treg proliferation, may be efficacious in ITP patients.     

Viral polymorphism in human papillomavirus types 33 and 35 and persistent and transient infection in the genital tract of women

BACKGROUND: Genetic polymorphism in human papillomavirus (HPV)-33 and -35 was investigated in 1055 sexually active women (732 human immunodeficiency virus [HIV] seropositive and 323 HIV seronegative). METHODS: Consecutive genital specimens obtained at 6-month intervals were screened for HPV-33 and -35 by use of MY09-MY11. HPV-33 and -35 isolates from 95 women were analyzed by polymerase chain reaction sequencing of the long control region (LCR), E6, and E7. RESULTS: For HPV-33, 101 (20%) of 506 nucleotides in the LCR were variable, compared with 10 (2.1%) of 483 nucleotides in E6 (P<.001) and 6 (1.9%) of 324 nucleotides in E7 (P<.001). For HPV-35, the proportion of variable nucleotide sites was similar between the LCR and both E6 (P=.54) and E7 (P=.33). The presence of a 78-base pair deletion in HPV-33 (relative risk [RR], 1.8 [95% confidence interval [CI], 1.2-2.7]) and the presence of nonsynonymous E7 variations in HPV-35 (RR, 2.6 [95% CI, 1.4-4.6]) were associated with persistence. When the data for HPV-33 and -35 were combined, infection by HPV isolates with nonsynonymous E7 variations (RR, 2.3 [95% CI, 1.6-3.4]; P=.001) and ethnicity (P=.04) were associated with persistence, whereas age (P = .14) and HIV infection/CD4 cell count status (P=.12) were not significantly associated with persistence, by logistic regression analysis. CONCLUSION: HPV-33 and -35 polymorphism was different between types and was associated with persistence of HPV infection.     

Association between alcohol consumption and both osteoporotic fracture and bone density

Objective

Alcoholism is a risk factor for osteoporotic fractures and low bone density, but the effects of moderate alcohol consumption on bone are unknown. We performed a systematic review and meta-analysis to assess the associations between alcohol consumption and osteoporotic fractures, bone density and bone density loss over time, bone response to estrogen replacement, and bone remodeling.

Methods

MEDLINE, Current Contents, PsychINFO, and Cochrane Libraries were searched for studies published before May 14, 2007. We assessed quality using the internal validity criteria of the US Preventive Services Task Force.

Results

We pooled effect sizes for 2 specific outcomes (hip fracture and bone density) and synthesized data qualitatively for 4 outcomes (non-hip fracture, bone density loss over time, bone response to estrogen replacement, and bone remodeling). Compared with abstainers, persons consuming from more than 0.5 to 1.0 drinks per day had lower hip fracture risk (relative risk = 0.80 [95% confidence interval, 0.71-0.91]), and persons consuming more than 2 drinks per day had higher risk (relative risk = 1.39 [95% confidence interval, 1.08-1.79]). A linear relationship existed between femoral neck bone density and alcohol consumption. Because studies often combined moderate and heavier drinkers in a single category, we could not assess relative associations between alcohol consumption and bone density in moderate compared with heavy drinkers.

Conclusion

Compared with abstainers and heavier drinkers, persons who consume 0.5 to 1.0 drink per day have a lower risk of hip fracture. Although available evidence suggests a favorable effect of alcohol consumption on bone density, a precise range of beneficial alcohol consumption cannot be determined.     

Histamine reduces gap junctional communication of human tonsil high endothelial cells in culture

The regulation of gap junctional communication by histamine was studied in primary cultures of human tonsil high endothelial cells (HUTECs). We evaluated intercellular communication, levels, state of phosphorylation, and cellular distribution of gap junction protein subunits, mainly connexin (Cx)43. Histamine induced a time-dependent reduction in dye coupling (Lucifer yellow) associated with reduction in connexin43 localized at cell-cell appositions (immunofluorescence), without changes in levels and phosphorylation state of connexin43 (immunoblots). These effects were prevented with chlorpheniramine, an H1 receptor blocker; indomethacin, a cyclooxygenase blocker; or GF109203X, a protein kinase C inhibitor. Treatment with phorbol myristate acetate, a protein kinase C activator, and 4bromo (4Br)-A23187, a calcium ionophore, mimicked the histamine-induced effects on dye coupling. 8Bromo-cAMP doubled the dye coupling extent and prevented the histamine-induced reduction in incidence of dye coupling. After 24-h histamine treatment, known to desensitize H1 receptors, reapplication of histamine increased cell coupling in a way prevented by ranitidine, an H2 receptor blocker. Thus, activation of H1 and H2 receptors, which increase intracellular levels of free Ca2+ and cAMP, respectively, may affect gap junctional communication in opposite ways. Stabilization of actin filaments with phalloidine diminished but did not totally prevent histamine-induced cell shape changes and reduction in dye coupling. Hence, the histamine-induced reduction in gap junctional communication between HUTEC is mediated by cytoskeleton-dependent and -independent mechanisms and might contribute to modulate endothelial function in lymphoid tissue.     

Assessing Univentricular Function in Adult Fontan Using 3D Echocardiography

Objective: To determine the accuracy of assessing univentricular function in adult Fontan patients using three-dimensional (3D) volumetric echocardiography. Design: A prospective observational study in an adult Fontan patient cohort. Setting: University Hospitals Birmingham, NHS Foundation Trust. Patients: 26 patients were enrolled in the study all aged over 18 years, possessing the Fontan anatomy, with no contraindications to Cardiac Magnetic Resonance (CMR) imaging and in sinus rhythm. Intervention: All patients underwent transthoracic echocardiography using a Philips EPIQ 7 and X5-1 transducer. End diastolic volume (EDV), end systolic volume (ESV), stroke volume (SV) and ejection fraction (EF) were obtained using two dimensional (2D) and 3D acquisitions. CMR was performed within 3 months according to standard protocols. Outcome Measures: The agreement and correlation between 2D, 3D and CMR derived parameters were determined by Bland and Altman analysis and Pearson’s correlation coefficient method. The inter-observer variability was also assessed for all three modalities. Results: 3D volumetric acquisitions of the single ventricle were feasible in 18/26 (69%) patients. 3D volumes strongly correlated with CMR but with a systematic bias to underestimation: EDV r = 0.66, bias = –47.1 (–109.6 to 15.2); ESV r = 0.82, bias = – 19.4 (–59.9 to 21.1); EF r = 0.73, –1.56 (–18.8 to 15.7) and SV r = 0.32, –27.7 (– 70.2 to 14.7). Inter-observer variability was lowest with CMR, when compared to echocardiographic techniques. The inter-observer variability for 3D when compared with 2D echocardiography was lower across all parameters except EDV. Conclusions: 3D volumes correlate strongly with CMR and may be used for serial assessment of univentricular function. However, 3D volumes on echo are not interchangeable with CMR due to systematic underestimation of volume.