Single site pacing through the anterior interventricular vein in a patient with a mechanic tricuspid valve

Transvenous endocardial pacing through classical implantation of a pace/sensing lead in the right ventricle is strictly contraindicated in patients with a mechanical tricuspid valve. Usually permanent pacing is achieved by an epimyocardial surgical approach. We hereby describe the implantation of a single site left ventricle pacing lead in the anterior interventricular vein in a 60 year-old woman with symptomatic bradycardia, permanent atrial fibrillation, and mechanical tricuspid valve. The described use of left ventricle pacing through a coronary vein lead, in a patient with favorable venous anatomy, provided (through a minimal invasive approach) effective with a low and stable threshold.     

Genetic markers for diagnosis and pathogenesis of Alzheimer's disease

Alzheimer's disease (AD) is the most common form of dementia in the elderly and represents an important and increasing clinical challenge in terms of diagnosis and treatment. Mutations in the genes encoding amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) are responsible for early-onset autosomal dominant AD. The ε4 allele of the apolipoprotein E (APOE) gene has been recognized as a major genetic risk factor for the more common, complex, late-onset AD. Fibrillar deposits by phosphorylated tau are also a key pathological feature of AD. The retromer complex also has been reported to late-onset AD. More recently, genome-wide association studies (GWASs) identified putative novel candidate genes associated with late-onset AD. Lastly, several studies showed that circulating microRNAs (miRNAs) in the cerebrospinal fluid (CSF) and blood serum of AD patients can be used as biomarkers in AD diagnosis. This review addresses the advances and challenges in determining genetic and diagnostic markers for complex AD pathogenesis.     

Impact of chronicity of injury on the proportion of mesenchymal stromal cells derived from anterior cruciate ligaments

Background aimsThe graft-healing potential of mesenchymal stromal cells (MSCs) derived from the remnants of ruptured anterior cruciate ligaments (ACLs) after ACL reconstruction may depend on the chronicity of the injury. The aim of this study was to assess the quantitative and phenotypic differences between MSCs isolated from ACL remnants in patients with (sub)acute and chronic tearing.MethodsTorn ACL remnants were harvested during ACL reconstruction from 41 patients, 24 with (sub)acute ACL (<6 months from injury to surgery) and 17 with chronic ACL (time interval >6 months) tears. MSCs isolated from these samples were assessed for quantitative and phenotypic differences, and the correlation between the proportion of MSCs and the chronicity of ACL tear was evaluated.ResultsAt passage 0, the mean proportion of MSCs (CD34⁻, CD44⁺, CD90⁺ and CD105⁺) was higher in (sub)acute than in chronic ACL tear samples (20.69% ± 7.82% versus 9.85% ± 8.01%, P < 0.001). At passages 1 and 2, however, MSC proportions did not differ significantly in the two groups. Time interval showed a negative correlation with MSC proportion only at passage 0 (r = −0.505, P < 0.001). The optimal cutoff value for time from injury to surgery yielding <10% freshly isolated ACL-MSCs, a percentage expected to have low tissue healing potential, was 23.5 months.ConclusionsThe proportion of freshly isolated MSCs was higher in samples from patients with (sub)acute tearing than in chronic ACL tearing and negatively correlated with the time interval between trauma and surgery.     

Expression of zebrafish anterior gradient 2 in the semicircular canals and supporting cells of otic vesicle sensory patches is regulated by Sox10

AGR2 is a member of the protein disulfide isomerase (PDI) family, which is implicated in cancer cell growth and metastasis, asthma, and inflammatory bowel disease. Despite the contributions of this protein to several biological processes, the regulatory mechanisms controlling expression of the AGR2 gene in different organs remain unclear. Zebrafish anterior gradient 2 (agr2) is expressed in several organs, including the otic vesicles that contain mucus-secreting cells. To elucidate the regulatory mechanisms controlling agr2 expression in otic vesicles, we generated a Tg(− 6.0 k agr2:EGFP) transgenic fish line that expressed EGFP in a pattern recapitulating that of agr2. Double immunofluorescence studies were used to demonstrate that Agr2 and GFP colocalize in the semicircular canals and supporting cells of all sensory patches in the otic vesicles of Tg(− 6.0 k agr2:EGFP) embryos. Transient/stable transgenic analyses coupled with 5′-end deletion revealed that a 100 bp sequence within the − 2.6 to − 2.5 kbp region upstream of agr2 directs EGFP expression specifically in the otic vesicles. Two HMG-binding motifs were detected in this region. Mutation of these motifs prevented EGFP expression. Furthermore, EGFP expression in the otic vesicles was prevented by knockdown of the sox10 gene. This corresponded with decreased agr2 expression in the otic vesicles of sox10 morphants during different developmental stages. Electrophoretic mobility shift assays were used to show that Sox10 binds to HMG-binding motifs located within the − 2.6 to − 2.5 kbp region upstream of agr2. These results demonstrate that agr2 expression in the otic vesicles of zebrafish embryos is regulated by Sox10.     

The application of musculoskeletal modeling to investigate gender bias in non-contact ACL injury rate during single-leg landings

The central tenet of this study was to develop, validate and apply various individualised 3D musculoskeletal models of the human body for application to single-leg landings over increasing vertical heights and horizontal distances. While contributing to an understanding of whether gender differences explain the higher rate of non-contact anterior cruciate ligament (ACL) injuries among females, this study also correlated various musculoskeletal variables significantly impacted by gender, height and/or distance and their interactions with two ACL injury-risk predictor variables; peak vertical ground reaction force (VGRF) and peak proximal tibia anterior shear force (PTASF). Kinematic, kinetic and electromyography data of three male and three female subjects were measured. Results revealed no significant gender differences in the musculoskeletal variables tested except peak VGRF (p = 0.039) and hip axial compressive force (p = 0.032). The quadriceps and the gastrocnemius muscle forces had significant correlations with peak PTASF (r = 0.85, p < 0.05 and r = ? 0.88, p < 0.05, respectively). Furthermore, hamstring muscle force was significantly correlated with peak VGRF (r = ? 0.90, p < 0.05). The ankle flexion angle was significantly correlated with peak PTASF (r = ? 0.82, p < 0.05). Our findings indicate that compared to males, females did not exhibit significantly different muscle forces, or ankle, knee and hip flexion angles during single-leg landings that would explain the gender bias in non-contact ACL injury rate. Our results also suggest that higher quadriceps muscle force increases the risk, while higher hamstring and gastrocnemius muscle forces as well as ankle flexion angle reduce the risk of non-contact ACL injury.     

Numerical simulations of the blood flow in the patient-specific arterial cerebral circle region

The Cerebral Circle Region, also known as the Circle of Willis (CoW), is a loop of arteries that form arterial connections between supply arteries to distribute blood throughout the cerebral mass. Among the population, only 25% to 50% have a complete system of arteries forming the CoW. 3D time-varying simulations for three different patient-specific artery anatomies of CoW were performed in order to gain a better insight into the phenomena existing in the cerebral blood flow. The models reconstructed on the basis of computer tomography images start from the aorta and include the largest arteries that supply the CoW and the arteries of CoW. Velocity values measured during the ultrasound examination have been compared with the results of simulations. It is shown that the flow in the right anterior artery in some cases may be supplied from the left internal carotid artery via the anterior communicating artery. The investigations conducted show that the computational fluid dynamic tool, which provides high resolution in both time and space domains, can be used to support physicians in diagnosing patients of different ages and various anatomical arterial structures.     

Vax基因与视觉神经系统的早期发育

视觉神经系统的发育与形成是一个相当复杂的过程,其基因调控机理是神经发育生物学领域的研究热点.Vax基因家族是新近发现的一类与视觉神经系统发育密切相关的同源异型盒基因,调控前脑、眼原基、视泡、视柄以及视网膜的发育.Vax-1参与色素上皮和视柄的分化;Vax-2则在视网膜及视神经背腹轴建立方面起重要作用.Vax基因的研究将对阐明视觉神经系统发育调控机制提供新的认识.     

Total Hip Arthroplasty: Direct Anterior Approach Versus Posterior Approach in the First Year of Practice

BackgroundThe direct anterior approach (DAA) for total hip arthroplasty (THA) has been popularized as a less invasive technique, however outcomes within the first year of practice after fellowship have not been investigated. The primary aim was to determine differences in complications and outcomes between DAA and posterior approach (PA) in the first year of practice. The secondary aim was to determine if there was a learning curve factor in DAA and PA after fellowship training.MethodsTHA cases performed by two surgeons during their first year of practice were reviewed. Overall, 181 THAs (91 DAA, 90 PA) in 168 patients, were performed. Intraoperative differences (blood loss, operative time), hospital stay, complications, reoperations, and revisions were compared.ResultsOverall surgical complications were similar between DAA and PA (11% vs. 9%, p=0.64), but complication profiles were different: dislocation (1% vs. 4%, p=0.17), intraoperative femoral fracture (2% vs. 1%, p=0.32), postoperative periprosthetic fractures (2% vs. 3%, p=0.64). neuropraxia (3% vs. 0%, p=0.08). There was no difference in rate of reoperation (1% vs. 3%, p=0.31). There was a difference in rate of revision at final follow-up (0% vs. 6%, p=0.02). DAA consisted of longer operative time (111 vs. 99 minutes; p<0.001), however was only significant in the first 50 cases (p<0.001), while the subsequent cases were similar (p=0.31). There was no difference in the first 50 cases compared to the subsequent cases for either approach regarding blood loss, complications, reoperations, or revisions.ConclusionDAA and PA for THA performed within the first year of practice exhibit similarly low complication rates, but complication profiles are different. In our series, PA did demonstrate a higher risk of revision at final follow-up. A learning curve is not unique to the DAA. Both DAA and PA THA exhibited a learning curve in the first 50 cases performed at the start of a surgeon’s practice. Level of Evidence: III     

猫扣带回前部内脏伤害感受神经元的膜电学特性

目的：研究猫扣带回前部内脏大神经刺激相关神经元的膜电生理特性,以便从神经元水平进一步了解大脑皮质内脏伤害感受的特性及机制,为痛觉理论“特异性学说”提供新的实验依据。方法：应用在体玻璃微电极细胞内电位记录技术及细胞内注入极化电流的方法,测量和计算神经元的膜电学参数。结果：将20只猫扣带回前部176个内脏大神经刺激相关神经元,分为内脏伤害(148个)和非伤害(28个)感受神经元。发现它们在膜电阻、时间常数、膜电容及I—V曲线等方面存在差异。注入去极化电流引发的放电幅值及频率也存在差异。结论：扣带回前部内脏伤害与非伤害感受神经元可能在细胞膜结构、细胞大小等形态学方面存有差别。     

Cholesterol trafficking and raft-like membrane domain composition mediate scavenger receptor class B type 1-dependent lipid sensing in intestinal epithelial cells

Scavenger receptor Class B type 1 (SR-B1) is a lipid transporter and sensor. In intestinal epithelial cells, SR-B1-dependent lipid sensing is associated with SR-B1 recruitment in raft-like/ detergent-resistant membrane domains and interaction of its C-terminal transmembrane domain with plasma membrane cholesterol. To clarify the initiating events occurring during lipid sensing by SR-B1, we analyzed cholesterol trafficking and raft-like domain composition in intestinal epithelial cells expressing wild-type SR-B1 or the mutated form SR-B1-Q445A, defective in membrane cholesterol binding and signal initiation. These features of SR-B1 were found to influence both apical cholesterol efflux and intracellular cholesterol trafficking from plasma membrane to lipid droplets, and the lipid composition of raft-like domains. Lipidomic analysis revealed likely participation of d18:0/16:0 sphingomyelin and 16:0/0:0 lysophosphatidylethanolamine in lipid sensing by SR-B1. Proteomic analysis identified proteins, whose abundance changed in raft-like domains during lipid sensing, and these included molecules linked to lipid raft dynamics and signal transduction. These findings provide new insights into the role of SR-B1 in cellular cholesterol homeostasis and suggest molecular links between SR-B1-dependent lipid sensing and cell cholesterol and lipid droplet dynamics.