A rare case of arrhythmogenic right ventricular cardiomyopathy associated with LAMA2 mutation: A case report and literature review

BackgroundArrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable heart muscle disorder that predominantly affects the right ventricle. Mutations in genes that encode components of desmosomes, the adhesive junctions that connect cardiomyocytes, are the predominant cause of ARVC. A case with novel heterozygous mutation in the LAMA2 gene is reported here. The protein encoded by LAMA2 gene is the α2 chain of laminin-211 protein, which establishes a stable relationship between the muscle fiber membrane and the extracellular matrix. We explored the potential mechanism and the relationship between the mutation and ARVC.Case PresentationAt the age of 8, the patient developed syncope and palpitation after exercise. Dynamic electrocardiogram recorded continuous premature ventricular beats, and MRI showed the right ventricle was significantly enlarged and there were many localized distensions at the edge of the right ventricular wall. The patient was diagnosed with ARVC and received heart transplantation at the age of 14 due to severe heart dysfunction. The myocardial histological pathological staining revealed a large amount of fibrosis and adipose migration. Whole exome sequencing (WES) identified the heterozygous mutation in the LAMA2 gene [NM_000426.3: c.8842G > A (p.G2948S)]. This is the first report of these variants. Analysis was performed on genetic disorders to reveal splice site changes and damage to protein structure. LAMA2 p.G2948S predicted unstable protein structure and impaired function. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were established. RNA-seq and the western blot were performed on IPSC-CMs to explore the ARVC-related signaling pathway.ConclusionThis is the first case report to describe an ARVC phenotype in patients possessing a novel LAMA2 c.8842G > A (p.G2948S) mutation. Our results aid in understanding of the pathogenesis of ARVC. The molecular mechanism of LAMA2 leading to ARVC disease still needs further study

Effect of APOE ɛ4 Status on Brain Amyloid-β and Cognitive Function in Amnestic and Nonamnestic Mild Cognitive Impairment: A 18F Florbetapir PET-CT Study

Mild cognitive impairment (MCI) is recognized as a predementia syndrome caused by multiple etiologies and nonmemory symptoms in MCI have recently gained increasing attention. However, the pattern of Aβ deposition and the effect of APOE (apolipoprotein E, APOE) ε4 on cognitive impairment in amnestic MCI (aMCI) and nonamnestic MCI (naMCI) patients has not been demonstrated. In this work, the amyloid-β (Aβ) load by [$^{18}$F]florbetapir PET imaging and cognitive performance is compared by comprehensive neuropsychological scales in participants with different MCI types or different APOE ε4 carriage status. According to the Aβ positivity and results of voxel-wise analysis, higher Aβ loads are observed in aMCI patients than naMCI patients, especially aMCI patients with APOE ε4. Additionally, it is observed that memory domain Z scores show a strong negative correlation with global florbetapir SUVR in the aMCI group (r = – 0.352, p < 0.001) but not in the naMCI group (r = –0.016, p = 0.924). Moreover, this correlation is independent of APOE e4 carriage status. This study aims to identify high-risk groups at an early stage of AD(Alzheimer's Disease, AD) through cognitive performance and APOE ε4 carrier status, which can be important for guiding clinical intervention trials

POEMS Syndrome: Real World Experience in Diagnosis and Systemic Therapy - 108 Patients Multicenter Analysis

POEMS syndrome, a rare plasma cell disorder, is challenging both in the diagnostic and therapeutic management. We present real word retrospective analysis of 108 cases analyzing clinical features and therapeutic modes. We compare our results with the available literature. This is the first description with such wide use of proteasome inhibitors in first line treatment. POEMS (Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) syndrome is a rare and challenging plasma cell disorder, both in the diagnostic and therapeutic management of the disease. Currently, the literature on POEMS is sparse with most evidence being case reports and small case studies. We present a retrospective real world experience of 108 patients with POEMS. We analyzed the clinical features and therapeutic interventions. Regarding clinical features, our findings demonstrated that skin lesions, thrombocythemia and polycythemia were present less frequently than reported previously. Regarding clinical interventions, this is one of the largest analyses of front line treatment in POEMS and the first one to include frequent utilization of proteasome inhibitors (37%). Bortezomib monotherapy was the most effective therapy achieving complete remission/very good partial remissions (CR/VGPR) in 69% of patients. Thirty percent of patients proceeded to planned autologous stem cell transplant (ASCT) as part of the front-line treatment resulting in statistically superior progression-free (PFS) and overall survival (OS) compared to non-ASCT treated patients (P= .003). In multivariate analysis, anemia, thrombocytopenia, and as age over 60 were associated with a negative impact on patient outcomes

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Multi-Objective Optimization of a Permanent Magnet Actuator for High Voltage Vacuum Circuit Breaker Based on Adaptive Surrogate Modeling Technique

A novel mono-stable permanent magnet actuator (PMA) for high voltage vacuum circuit breaker (VCB) and its optimal design method are proposed in this paper. The proposed PMA is featured with a structure of separated magnetic circuits, which makes the holding part and closing driving part work independently without interference. The application of an auxiliary breaking coil decreases the response time in the initial phase of opening operation, and an external disc spring is adopted to accelerate the opening movement, which makes the PMA meet the fast-breaking requirement of high voltage VCB. As calculating the characteristics of the PMA accurately through numerical simulation is a time-consuming process, a multi-objective optimization (MOO) algorithm based on surrogate modeling technique and adaptive samples adding strategy are proposed to reduce the workload of numerical simulations during optimization. Firstly, initial surrogate models are constructed and evaluated, and then iteratively updated to improve their global approximating abilities. Secondly, according to the approximate MOO results obtained by the global surrogate models, additional samples are added to constantly update the surrogate models to gradually improve the models&rsquo; local accuracies in optimal solution regions and finally guide the algorithm to the true Pareto front. The efficiency and accuracy of the proposed algorithm are verified by test functions. By applying the optimization strategy to the design of the proposed PMA, a set of satisfying Pareto optimal solutions, which improve the overall performance of the PMA obviously, can be derived at a reasonable computation cost

Effect of Small Organic Acid Anions on the Adsorption of Phosphate Anions onto Synthetic Goethite from Aqueous Solution

Batch experiments were conducted to study the effect of small organic acids (citric, oxalic and acetic) on the removal of phosphate anions from aqueous systems using synthesized goethite as the adsorbent. The results showed that phosphate anion adsorption was most significantly inhibited by citric among the three organic acids studied. Phosphate anion adsorption was affected at pH values below 6.5. The relationship between citrate anionpromoted goethite dissolution and citrate anion-suppressed phosphate anion adsorption in equilibrated goethite–phosphate anion–citric acid systems with different contact orders was studied. The results indicated that there is an obvious correlation between the suppression of phosphate anion adsorption and the dissolution of goethite. It is proposed that competition for binding sites play a key role in the reduction of phosphate anion adsorption by citric acid

Comparison and Analysis of Dual Stator Permanent Magnet Vernier Machines with Different Pole/Slot Combinations for Low Speed Direct Drive Applications

Permanent magnet vernier machine (PMVM) based on flux modulation principle has attracted increasing attention in low-speed direct-drive applications due to its high torque capability. A dual-stator PMVM topology with sandwiched spoke-array PM rotor is presented to produce higher air-gap flux density and larger torque in this paper, and the space utilization and the energy conversion efficiency are improved significantly. Two representative dual-stator PMVMs (DS-PMVMs) are designed with this topology, the pole/slot combinations and gear ratios of which are 18 slots/30 poles and 18 slots/28 poles, 5 and 3.5, respectively. In order to reveal the advantages of the proposed topology and assess the torque characteristics of the proposed machines with different pole/slot combinations, the electromagnetic characteristics of these two machines are quantitatively compared and analyzed by using finite element method (FEM). The results demonstrate that the 18 slots/28 poles DS-PMVM can offer higher output torque, lower torque ripples, lower cogging torque and higher power factor owing to its optimal pole/slot combination. In addition, the unbalanced magnetic pulls (UMPs) of the two machines are also investigated, and the UMP of the 18 slots/30 poles DS-PMVM is smaller than that of its counterpart due to its symmetrical winding