Targeted regeneration of bone in the osteoporotic human femur.

We have recently developed image processing techniques for measuring the cortical thicknesses of skeletal structures in vivo, with resolution surpassing that of the underlying computed tomography system. The resulting thickness maps can be analysed across cohorts by statistical parametric mapping. Applying these methods to the proximal femurs of osteoporotic women, we discover targeted and apparently synergistic effects of pharmaceutical osteoporosis therapy and habitual mechanical load in enhancing bone thickness

Advances for Treating in-Hospital Cardiac Arrest: Safety and Effectiveness of a New Automatic External Cardioverter-Defibrillator

OBJECTIVES: The purpose of this study was to prospectively analyze the performance and safety of a new programmable, fully automatic external cardioverter-defibrillator (AECD) in a European multicenter trial. BACKGROUND Although, the response time to cardiac arrest (CA) is a major determinant of mortality and morbidity, in-hospital strategies have not significantly changed during the last 30 years. METHODS: Patients (n = 117) at risk of CA in monitored wards (n = 51) and patients undergoing electrophysiologic testing or implantable cardioverter-defibrillator (ICD) implantation (n = 66) were enrolled. The accuracy of the automatic response of the device to any change of rhythm (lasting >1 s and >4 beats) was confirmed by reviewing the simultaneously recorded Holter data and the programmed parameters. RESULTS: During 1,240 h, 1,988 episodes of rhythm changes were documented. A total of 115 episodes lasted > or =10 s or needed treatment (pacing, n = 32; ICD, n = 51; AECD, n = 35) for termination. The device detected ventricular tachyarrhythmias with a sensitivity of 100% and specificity of 97.6% (true negatives, n = 1,454; true positives, n = 499; false positives, n = 35; false negatives, n = 0). The false positives were all caused by T-wave oversensing during ventricular pacing. There were no complications or adverse events. The mean response time was 14.4 s for those episodes needing a full charge of the capacitor. CONCLUSIONS: This new AECD is safe and effective in detecting, monitoring, and treating spontaneous arrhythmias. This fully automatic device shortens the response time to treatment, and it is likely that it will significantly improve the outcome of patients with in-hospital CA

JAZF1, A Novel p400/TIP60/NuA4 Complex Member, Regulates H2A.Z Acetylation at Regulatory Regions

Histone variants differ in amino acid sequence, expression timing and genomic localization sites from canonical histones and convey unique functions to eukaryotic cells. Their tightly controlled spatial and temporal deposition into specific chromatin regions is accomplished by dedicated chaperone and/or remodeling complexes. While quantitatively identifying the chaperone complexes of many human H2A variants by using mass spectrometry, we also found additional members of the known H2A.Z chaperone complexes p400/TIP60/NuA4 and SRCAP. We discovered JAZF1, a nuclear/nucleolar protein, as a member of a p400 sub-complex containing MBTD1 but excluding ANP32E. Depletion of JAZF1 results in transcriptome changes that affect, among other pathways, ribosome biogenesis. To identify the underlying molecular mechanism contributing to JAZF1's function in gene regulation, we performed genome-wide ChIP-seq analyses. Interestingly, depletion of JAZF1 leads to reduced H2A.Z acetylation levels at > 1000 regulatory sites without affecting H2A.Z nucleosome positioning. Since JAZF1 associates with the histone acetyltransferase TIP60, whose depletion causes a correlated H2A.Z deacetylation of several JAZF1-targeted enhancer regions, we speculate that JAZF1 acts as chromatin modulator by recruiting TIP60's enzymatic activity. Altogether, this study uncovers JAZF1 as a member of a TIP60-containing p400 chaperone complex orchestrating H2A.Z acetylation at regulatory regions controlling the expression of genes, many of which are involved in ribosome biogenesis

Is abnormal myocardial repolarization associated with the occurrence of malignant tachyarrhythmias in Takotsubo cardiomyopathy?

Background: Abnormalities of cardiac repolarization are a hallmark of Takotsubo cardiomyopathy (TC), but their association with the occurrence of syncope and ventricular tachyarrhythmias is unknown. This study sought to assess the relationship between myocardial repolarization and malignant tachyarrhythmias in TC.Methods: Clinical data and electrocardiographic repolarization parameters of 28 patients with TC and ventricular tachyarrhythmias (n = 26) or syncope (n = 2) were compared to data from 20 randomly selected patients with TC but without ventricular tachyarrhythmias or syncope.Results: Study patients had signifi cantly lower ejection fraction (EF) compared with controls (35 ± 14% vs. 46 ± 10%, p = 0.006). On day 1, no signifi cant differences in repolarization parameters were observed. However, in the subgroup with ventricular fi brillation ([VF]; n = 10), Tpeak-Tend in lead V6 was significantly prolonged (97 ± 20 vs. 85 ± 19 ms; p = 0.04). Similarly, in the subgroup with torsade de pointes ([TdP]; n = 5) Tpeak-Tend in lead V4 wasprolonged (127 ± 21 vs. 94 ± 27 ms; p = 0.001). On day 3, Tpeak-Tend in lead V3 (130 ± 51 vs. 105 ± 21 ms, p = 0.049) and Tpeak-Tend dispersion (56 ± 33 vs. 36 ± 21 ms; p = 0.03) were signifi cantly longer in study patients. The difference in Tpeak-Tend in lead V3 was borderline in the VF subgroup, but significant in the subgroup with TdP. The latter grouphad also longer Tpeak-Tend in lead V4 and longer corrected QT interval in leads V3 and V4.Conclusions: Patients with TC who experience malignant tachyarrhythmias have lower EF and a more pronounced alteration of the spatial dispersion of ventricular repolarization

Randomized, double blind study of non-excitatory, cardiac contractility modulation electrical impulses fr symptomatic heart failure

AIMS: We performed a randomized, double blind, crossover study of cardiac contractility modulation (CCM) signals in heart failure patients. METHODS AND RESULTS: One hundred and sixty-four subjects with ejection fraction (EF) < 35% and NYHA Class II (24%) or III (76%) symptoms received a CCM pulse generator. Patients were randomly assigned to Group 1 (n = 80, CCM treatment 3 months, sham treatment second 3 months) or Group 2 (n = 84, sham treatment 3 months, CCM treatment second 3 months). The co-primary endpoints were changes in peak oxygen consumption (VO2,peak) and Minnesota Living with Heart Failure Questionnaire (MLWHFQ). Baseline EF (29.3 +/- 6.7% vs. 29.8 +/- 7.8%), VO2,peak (14.1 +/- 3.0 vs. 13.6 +/- 2.7 mL/kg/min), and MLWHFQ (38.9 +/- 27.4 vs. 36.5 +/- 27.1) were similar between the groups. VO2,peak increased similarly in both groups during the first 3 months (0.40 +/- 3.0 vs. 0.37 +/- 3.3 mL/kg/min, placebo effect). During the next 3 months, VO2,peak decreased in the group switched to sham (-0.86 +/- 3.06 mL/kg/min) and increased in patients switched to active treatment (0.16 +/- 2.50 mL/kg/min). MLWHFQ trended better with treatment (-12.06 +/- 15.33 vs. -9.70 +/- 16.71) during the first 3 months, increased during the second 3 months in the group switched to sham (+4.70 +/- 16.57), and decreased further in patients switched to active treatment (-0.70 +/- 15.13). A comparison of values at the end of active treatment periods vs. end of sham treatment periods indicates statistically significantly improved VO2,peak and MLWHFQ (P = 0.03 for each parameter). CONCLUSION: In patients with heart failure and left ventricular dysfunction, CCM signals appear safe; exercise tolerance and quality of life (MLWHFQ) were significantly better while patients were receiving active treatment with CCM for a 3-month period