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Mutations in DES, encoding desmin protein, are associated with different kinds of skeletal and/or cardiac myopathies. However, it is unknown, whether DES mutations are associated with left ventricular hypertrabeculation (LVHT). Here, we performed a clinical examination and subsequent genetic analysis in a family, with two individuals presenting LVHT with conduction disease and skeletal myopathy. The genetic analysis revealed a novel small in‐frame deletion within the DES gene, p.Q113_L115del, affecting the α‐helical rod domain. Immunohistochemistry analysis of explanted myocardial tissue from the index patient revealed an abnormal cytoplasmic accumulation of desmin and a degraded sarcomeric structure. Cell transfection experiments with wild‐type and mutant desmin verified the cytoplasmic aggregation and accumulation of mutant desmin. Cotransfection experiments were performed to model the heterozygous state of the patients and revealed a dominant negative effect of the mutant desmin on filament assembly. DES:p.Q113_L115del is classified as a pathogenic mutation associated with dilated cardiomyopathy with prominent LVHT.  相似文献   
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Palatal involvement occurs commonly in patients with 22q11.2 Deletion Syndrome (22qDS), and includes palatal clefting and velopharyngeal dysfunction in the absence of overt or submucous clefts. The reported incidence and distribution of palatal abnormalities vary in the literature. The aim of this article is to revisit the incidence and presenting features of palatal abnormalities in a large cohort of patients with 22qDS, summarize the surgical treatments performed in this cohort, and provide an overview of surgical treatment protocols and management guidelines for palatal abnormalities in this syndrome. Charts of 1,121 patients seen through the 22q and You Center at the Children's Hospital of Philadelphia were reviewed for palatal status, demographic factors, deletion size, and corrective surgical procedures. Statistical analysis was performed using Pearson's chi‐squared test to identify differences between gender, deletion size, and palatal abnormality. Of the patients with complete evaluations, 67% were found to have a palatal abnormality. The most common finding was velopharyngeal dysfunction in 55.2% of patients, and in 33.3% of patients, this occurred in the absence of palatal clefting. There was no significant difference in the incidence of palatal abnormalities by gender; however, a difference was noted among race (p < 0.01) and deletion sizes (p < 0.01). For example, Caucasian and Asian patients presented with a much higher prevalence of palatal abnormalities, and conversely those with nested deletions presented with a much lower rate of palatal defects. Overall, 26.9% of patients underwent palatal surgery, and the most common indication was velopharyngeal dysfunction. Palatal abnormalities are a hallmark feature of 22q11.2 Deletion Syndrome; understanding the incidence, presenting features, and treatment protocols are essential for practitioners counseling and treating families affected with this disorder.  相似文献   
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Abstract

The aim of this study is to evaluate the outcomes of single embryo transfer in patients with good ovarian reserve in the IVF program using time-lapse microscopy. This is a retrospective cohort study in a private IVF center in Russia. Comparison was done between 90 IVF cycles using time-lapse (study group) and 113 IVF cycles using standard culture (control group). Within each group, subgroups were selected with selective transfer of one embryo for 5 days (5SET) and elective transfer of one embryo for 5 days (5eSET). The primary outcome of the study was pregnancy rate. Secondary outcomes were miscarriage rates, live birth. Pregnancy rate did not significantly differ between the groups – 64.2% in the study group and control group. In the study group, the delivery rate was 54% in the subgroup 5eSET and 51.1% in the subgroup 5SET (p?=?.940). In the control group, the type of the embryo transfer significantly influenced on the delivery rate: in the 5eSET subgroup the birth rate was 54.4%, and in the 5SET subgroup it was 34.3% (p?=?.055; by Fisher's exact method p?=?.052). There were no adverse effects of the intervention. Selection of a single blastocyst based on information derived from time-lapse monitoring can help embryo selection for transfer.  相似文献   
156.

Purpose

The aim of our study was to analyze clinical and radiographic outcomes of operative management of L5 high-grade dysplastic spondylolisthesis with the apparatus for external transpedicular fixation (AETF), and to compare the results of its use for reduction and spondylodesis.

Methods

There were 13 patients with L5 dysplastic spondylolisthesis of grade 4 (Meyerding grading) and having a mean age of 25.0?±?3.6 years. The management included two stages: gradual reduction with the AETF, followed by either isolated anterior spondylodesis with the same AETF (group 1, n?=?8), or by spondylodesis using a combined method (internal transpedicular instrumentation and posterior lumbar interbody fusion [PLIF]) (group 2, n?=?5). Clinical evaluation included pain (VAS scale) and functional status (Oswestry questionnaire [ODI]). Reduction and fusion completeness were assessed radiographically after treatment and at a mean follow-up of 2.1?±?0.4 years.

Results

Initial slippage was reduced by 51.6 % with AETF and was of grade 1 or 2. Reduction made up 31.1 % at follow-ups (grade 2 or 3). Pain decreased by 57.6 % (p?<?0.01). The functional status improved. ODI decreased by 37.7 % (p?<?0.01) after treatment and by 41.7 % (p?<?0.01) at follow-ups. Fusion at the level of the involved segment was poor in group 1. All the cases fused in group 2.

Conclusions

The use of AETF for L5 high-grade dysplastic spondylolisthesis provides gradual controlled reduction of the slipped vertebra, decompression of cauda equine roots, and recovery of the local sagittal spinal column balance. It creates conditions for achieving stability of lumbosacral segments with combined spondylodesis (internal transpedicular instrumentation and PLIF). AETF is not suitable for spondylodesis due to a high rate of pseudarthrosis.
  相似文献   
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Transforming growth factor (TGF)-βs are plausible candidate tumor suppressors in the breast. They also have oncogenic activities under certain circumstances, however. Genetically altered mouse models provide powerful tools to analyze the complexities of TGF-βaction in the context of the whole animal. Overexpression of TGF-β can suppress tumorigenesis in the mammary gland, raising the possibility that use of pharmacologic agents to enhance TGF-β function locally might be an effective method for the chemoprevention of breast cancer. Conversely, loss of TGF-β response increases spontaneous and induced tumorigenesis in the mammary gland. This confirms that endogenous TGF-βs have tumor suppressor activity in the mammary gland, and suggests that the loss of TGF-β receptors seen in some human breast hyperplasias may play a causal role in tumor development.  相似文献   
160.
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