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Background: The authors aimed to determine whether electrical dental devices would interfere with the function of cardiac pacemakers or implantable cardioverter defibrillators (ICDs) in humans., Methods: The authors exposed asymptomatic nonpacemaker-dependent patients to commonly used electrical dental equipment (for example, battery-operated curing lights, ultrasonic baths, ultrasonic scalers, electric pulp testers, and electric toothbrushes) in an outpatient cardiology clinic. The authors operated dental devices at various distances and programmed cardiac devices to sense and pace. The authors obtained cardiac tracings using a cardiac programming unit and a cardiac provider who noted any interference interpreted the results in real time., Results: The authors enrolled 32 consecutive patients and tested 12 pacemakers and 20 ICDs. They did not observe any significant clinical interference in sensing and pacing functions in any patient; however, they noted minor interference without clinical impact in the telemetry from the cardiac programming unit during use of the ultrasonic scaler and bath., Conclusions: The findings of this prospective study suggest that electrical devices commonly used in dental practices do not interfere with the sensing and pacing of contemporary cardiac patients' pacemakers or ICDs. However, they do interfere with the telemetry from the cardiac programming unit, without any clinical impact on patient safety. These findings should help in the development of clinical guidelines regarding dental management of patients with pacemakers or ICDs., Practical Implications: Electrical dental devices (for example, ultrasonic baths, ultrasonic scalers) induced minor interference with programmers that interrogate cardiac devices implanted in patients; however, overall, dental devices do not appear to interfere with pacemakers' and defibrillators' pacing and sensing function., (Copyright © 2015 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Androgen receptor (AR) mutations in androgen insensitivity syndrome (AIS) are associated with a variety of clinical phenotypes. The aim of the present study was to compare the molecular properties and potential pathogenic nature of 8 novel and 3 recurrent AR variants with a broad variety of functional assays. Eleven AR variants (p.Cys177Gly, p.Arg609Met, p.Asp691del, p.Leu701Phe, p.Leu723Phe, p.Ser741Tyr, p.Ala766Ser, p.Arg775Leu, p.Phe814Cys, p.Lys913X, p.Ile915Thr) were analyzed for hormone binding, transcriptional activation, cofactor binding, translocation to the nucleus, nuclear dynamics, and structural conformation. Ligand-binding domain variants with low to intermediate transcriptional activation displayed aberrant Kd values for hormone binding and decreased nuclear translocation. Transcriptional activation data, FxxFF-like peptide binding and DNA binding correlated well for all variants, except for p.Arg609Met, p.Leu723Phe and p.Arg775Leu, which displayed a relatively higher peptide binding activity. Variants p.Cys177Gly, p.Asp691del, p.Ala766Ser, p.Phe814Cys, and p.Ile915Thr had intermediate or wild type values in all assays and showed a predominantly nuclear localization in living cells. All transcriptionally inactive variants (p.Arg609Met, p.Leu701Phe, p.Ser741Tyr, p.Arg775Leu, p.Lys913X) were unable to bind to DNA and were associated with complete AIS. Three variants (p.Asp691del, p.Arg775Leu, p.Ile915Thr) still displayed significant functional activities in in vitro assays, although the clinical phenotype was associated with complete AIS. The data show that molecular phenotyping based on 5 different functional assays matched in most (70%) but not all cases., (Copyright © 2013 S. Karger AG, Basel.)

Background: Physicians will increasingly encounter patients who require rhythm management devices but have venous obstructions that prevent conventional access. Alternate access options, such as thoracotomy or transiliac approaches, exist but are associated with greater cost and morbidity., Objective: The purpose of this study is to describe a novel method of vascular access that allows prepectoral placement of conventional pacing and defibrillation leads in patients with complex central venous occlusions., Methods: Eight patients with central venous occlusions were referred for device implantation. Inside-out central venous access (IOCVA) was obtained via a percutaneous femoral approach. A catheter-dilator system was advanced via the right atrium to the most central point of venous occlusion. The occluded vein segment was punctured with a directionally guided needle, which was advanced along intravascular or extravascular tissue planes to the subclavian region. A solid wire needle was oriented toward the skin surface and advanced through the soft tissues until it exists from the body. The wire was used to pull rigid dilators through the occluded segment. Standard transvenous leads were implanted though the newly created channel., Results: All patients with total central venous occlusions (4 superior vena cava, 4 brachiocephalic and bilateral subclavian) had successful, prepectoral device implants (4 left-sided, 1 single-chamber, 4 dual-chamber, 3 biventricular). No procedure-related complications occurred. All patients had normal device function at follow-up of 485 ± 542 days., Conclusion: IOCVA is an effective method of pacemaker and defibrillator implantation for patients with central venous occlusions. Further clinical evaluation of this novel method is needed., (Copyright © 2011 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Insertion of 3 to 4 mutations, based on in silico modelling, in a diverse set of natural miniproteins generates potent androgen receptor (AR) binders and a clear insight into the structure-activity relationship of such coactivator mimics concerning helix length.

The discovery and launch of non-steroidal ligands for estrogen receptors (ERs) and for androgen receptors (ARs) demonstrated the potential of these ligands as therapeutic agents. Based on these successes, substantial attention in the past ten years has been focused on identifying non-steroidal ligands for all of the classic steroid receptors. Non-steroidal ligands are currently in the discovery phase or in early clinical development for glucocorticoid, mineralocorticoid and progesterone receptors, and therefore must still provide evidence of their beneficial features over their steroidal counterparts. Although many new compounds for ERs and ARs are also undergoing discovery phase investigation or (early) development, none have been launched in the past ten years. The complexity of steering functional selectivity remains an ongoing challenge in the development on non-steroidal ligands.