Stochastic and alternating pacing paradigms to assess the stability of cardiac conduction.

Reentry, the most common cause of severe arrhythmias, is initiated by slow conduction and conduction block. Hence, evaluating conduction velocity and conduction block is of primary importance. However, the assessment of cardiac conduction safety in experimental and clinical settings remains elusive.

Mid-term survival of the Optimys short stem: A prospective case series of 500 patients.

Background: In recent years, there has been an increase in the number of total hip arthroplasty procedures in the younger patient population. This active group has higher expectations of their prosthesis in comparison to the older population, and there is a greater physical demand for the prosthesis. Short femoral stems were introduced to retain proximal bone stock and joint biomechanics and became more common to implant in this specific population.

Structure-function relationship of new peptides activating human Na1.1.

Na1.1 is an important pharmacological target as this voltage-gated sodium channel is involved in neurological and cardiac syndromes. Channel activators are actively sought to try to compensate for haploinsufficiency in several of these pathologies.

A link between agrin signalling and Ca3.2 at the neuromuscular junction in spinal muscular atrophy.

SMN protein deficiency causes motoneuron disease spinal muscular atrophy (SMA). SMN-based therapies improve patient motor symptoms to variable degrees. An early hallmark of SMA is the perturbation of the neuromuscular junction (NMJ), a synapse between a motoneuron and muscle cell.

Screening an In-House Isoquinoline Alkaloids Library for New Blockers of Voltage-Gated Na Channels Using Voltage Sensor Fluorescent Probes: Hits and Biases.

Voltage-gated Na (Na) channels are significant therapeutic targets for the treatment of cardiac and neurological disorders, thus promoting the search for novel Na channel ligands. With the objective of discovering new blockers of Na channel ligands, we screened an In-House vegetal alkaloid library using fluorescence cell-based assays. We screened 62 isoquinoline alkaloids (IA) for their ability to decrease the FRET signal of voltage sensor probes (VSP), which were induced by the activation of Na channels with batrachotoxin (BTX) in GH3b6 cells.

Generation of human induced pluripotent stem cell lines from three patients affected by Catecholaminergic Polymorphic ventricular tachycardia (CPVT) carrying heterozygous mutations in RYR2 gene.

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is an exercise and emotional stress-induced life-threatening inherited heart rhythm disorder, characterized by an abnormal cellular calcium homeostasis. Most reported cases have been linked to mutations in the gene encoding the type 2 ryanodine receptor gene, RYR2. We generated induced pluripotent stem cells (hiPSCs) from peripheral blood mononuclear cells (PBMC) from three CPVT-affected patients, two of them carrying p.

Short-term success of proximal bone stock preservation in short hip stems: a systematic review of the literature.

Total hip arthroplasty is performed more frequently in younger patients nowadays, making long-term bone stock preservation an important topic. A mechanism for late implant failure is periprosthetic bone loss, caused by stress shielding around the hip stem due to different load distribution. Short stems are designed to keep the physical loading in the proximal part of the femur to reduce stress shielding.

Dynamic trial fitting of the cup in press-fit total hip arthroplasty, a feasibility study.

Trial fitting of the cup during total hip arthroplasty (THA) is done by trial cups, which do not resemble the real press-fit obtained by the definitive implant. Our goal is to judge feasibility of the X-pander® in clinical practice ; a device developed to mimic the real press-fit obtained by the definitive cup, to ensure satisfactory press-fit. In this feasibility study 45 experienced orthopaedic surgeons from 7 European countries filled in a structured survey after 78 primary THA and 31 revision surgeries, using the X-pander instead of traditional trial cups.

Relational quality and uncertainty in common pool water management: an exploratory lab experiment.

If there is one certainty for the sustainable management of water resources is that facing uncertainty is an unavoidable matter. A concern that, in addition to the best available scientific knowledge and models, requires deep insights about the socio relational processes that underlie decision-making. Our objective here is to better understand if and how the socio relational environment in which decisions are made shapes decision-making under uncertainty in common pool water resource management.

Capsular closure versus unrepaired interportal capsulotomy after hip arthroscopy in patients with femoroacetabular impingement: results of a patient-blinded randomised controlled trial.

Background: Hip capsular management after hip arthroscopy remains a topic of debate. Most available current literature is of poor quality and are retrospective or cohort studies. As of today, no clear consensus exists on capsular management after hip arthroscopy.

Fluorescent- and tagged-protoxin II peptides: potent markers of the Na 1.7 channel pain target.

Background And Purpose: Protoxin II (ProTx II) is a high affinity gating modifier that is thought to selectively block the Na 1.7 voltage-dependent Na channel, a major therapeutic target for the control of pain. We aimed at producing ProTx II analogues entitled with novel functionalities for cell distribution studies and biochemical characterization of its Na channel targets.

Maurocalcin and its analog MCaE12A facilitate Ca2+ mobilization in cardiomyocytes.

Ryanodine receptors are responsible for the massive release of calcium from the sarcoplasmic reticulum that triggers heart muscle contraction. Maurocalcin (MCa) is a 33 amino acid peptide toxin known to target skeletal ryanodine receptor. We investigated the effect of MCa and its analog MCaE12A on isolated cardiac ryanodine receptor (RyR2), and showed that they increase RyR2 sensitivity to cytoplasmic calcium concentrations promoting channel opening and decreases its sensitivity to inhibiting calcium concentrations.

Functional Impact of BeKm-1, a High-Affinity hERG Blocker, on Cardiomyocytes Derived from Human-Induced Pluripotent Stem Cells.

I current, a major component of cardiac repolarization, is mediated by human -Related Gene (hERG, K11.1) potassium channels. The blockage of these channels by pharmacological compounds is associated to drug-induced long QT syndrome (LQTS), which is a life-threatening disorder characterized by ventricular arrhythmias and defects in cardiac repolarization that can be illustrated using cardiomyocytes derived from human-induced pluripotent stem cells (hiPS-CMs).

Dynamic trial fitting by an expanding trial cup does not jeopardize primary acetabular component stability.

Background: Trial fitting of the acetabular component in uncemented total hip replacement is traditionally done by trial cups. Since trial cups do not resemble the real press-fit obtained by the definitive cup, a dynamic trial inserter, called the X-pander ®, was developed to mimic the real amount of press-fit. However, the concern is raised of losing the initial press-fit by using the X-pander® due to pre-expansion of the acetabulum.

Inhibition of G protein-gated K channels by tertiapin-Q rescues sinus node dysfunction and atrioventricular conduction in mouse models of primary bradycardia.

Sinus node (SAN) dysfunction (SND) manifests as low heart rate (HR) and is often accompanied by atrial tachycardia or atrioventricular (AV) block. The only currently available therapy for chronic SND is the implantation of an electronic pacemaker. Because of the growing burden of SND in the population, new pharmacological therapies of chronic SND and heart block are desirable.

Consensus on Contouring Primary Breast Tumors on MRI in the Setting of Neoadjuvant Partial Breast Irradiation in Trials.

Purpose: Our purpose was to present and evaluate expert consensus on contouring primary breast tumors on magnetic resonance imaging (MRI) in the setting of neoadjuvant partial breast irradiation in trials.

Methods And Materials: Expert consensus on contouring guidelines for target definition of primary breast tumors on contrast-enhanced MRI in trials was developed by an international team of experienced breast radiation oncologists and a dedicated breast radiologist during 3 meetings. At the first meeting, draft guidelines were developed through discussing and contouring 2 cases.

The migration pattern and initial stability of the Optimys short stem in total hip arthroplasty: a prospective 2-year follow-up study of 33 patients with RSA.

Background And Purpose: The consensus that bone stock preservation and optimal restoration of offset and leg length is important in total hip arthroplasty is now widespread, especially for young and active patients. Short stems seem promising in this aspect, though implant stability is still of concern. This study looked at the migration pattern of the Optimys short stem through RSA analysis.

Endocrine and local signaling interact to regulate spermatogenesis in zebrafish: follicle-stimulating hormone, retinoic acid and androgens.

Retinoic acid (RA) is crucial for mammalian spermatogonia differentiation, and stimulates expression, a gene required for meiosis. Certain fish species, including zebrafish, have lost the gene. While RA still seems important for spermatogenesis in fish, it is not known which stage(s) respond to RA or whether its effects are integrated into the endocrine regulation of spermatogenesis.

Stereotactic 9-gauge vacuum-assisted breast biopsy, how many specimens are needed?

Purpose: To determine the minimum number of stereotactic 9-gauge vacuum-assisted biopsy specimens required to establish a final histopathological biopsy diagnosis of mammographically suspicious breast lesions.

Methods: This prospective single-center observational cohort study included 120 women referred for stereotactic vacuum-assisted biopsy of 129 mammographically suspicious lesions between December 2017 and October 2018. Stereotactic 9-gauge vacuum-assisted biopsy was performed, acquiring twelve specimens per lesion.

Knowledge-based and deep learning-based automated chest wall segmentation in magnetic resonance images of extremely dense breasts.

Purpose: Segmentation of the chest wall, is an important component of methods for automated analysis of breast magnetic resonance imaging (MRI). Methods reported to date show promising results but have difficulties delineating the muscle border correctly in breasts with a large proportion of fibroglandular tissue (i.e.

Chemical Synthesis, Proper Folding, Na Channel Selectivity Profile and Analgesic Properties of the Spider Peptide Phlotoxin 1.

Phlotoxin-1 (PhlTx1) is a peptide previously identified in tarantula venom ( species) that belongs to the inhibitory cysteine-knot (ICK) toxin family. Like many ICK-based spider toxins, the synthesis of PhlTx1 appears particularly challenging, mostly for obtaining appropriate folding and concomitant suitable disulfide bridge formation. Herein, we describe a procedure for the chemical synthesis and the directed sequential disulfide bridge formation of PhlTx1 that allows for a straightforward production of this challenging peptide.

Aptamer Efficacies for In Vitro and In Vivo Modulation of αC-Conotoxin PrXA Pharmacology.

The medical staff is often powerless to treat patients affected by drug abuse or misuse and poisoning. In the case of envenomation, the treatment of choice remains horse sera administration that poses a wealth of other medical conditions and threats. Previously, we have demonstrated that DNA-based aptamers represent powerful neutralizing tools for lethal animal toxins of venomous origin.