Chest wall and intrathoracic desmoid tumors: surgical experience and review of the literature

Desmoid tumors are fibroblastic/myofibroblastic neoplasms, which originate from musculo-aponeurotic structures and are classified as deep fibromatoses. Despite their benign histologic appearance and lack of metastatic potential, desmoid tumors may cause aggressive local infiltrations and compression of surrounding structures. They are often associated with female gender, familial adenomatous polyposis (FAP) and sporadically may occur at sites of previous trauma, scars or irradiation. Molecular studies have demonstrated that these patients are associated with a bi-allelic APC mutation in the affected tissue. Radical tumor resection with free margins remains the first therapy of choice. In cases with anatomical or technical limitations for a wide excision, radiation therapy represents a proven and effective alternative or supplementary treatment

Paleogene calcite compensation depth in the eastern subtropical Pacific: Answers and questions

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95436/1/palo1183.pd

X-linked hypomyelination with spondylometaphyseal dysplasia (H-SMD) associated with mutations in AIFM1

An X-linked condition characterized by the combination of hypomyelinating leukodystrophy and spondylometaphyseal dysplasia (H-SMD) has been observed in only four families, with linkage to Xq25-27, and recent genetic characterization in two families with a common AIFM1 mutation. In our study, 12 patients (6 families) with H-SMD were identified and underwent comprehensive assessment accompanied by whole-exome sequencing (WES). Pedigree analysis in all families was consistent with X-linked recessive inheritance. Presentation typically occurred between 12 and 36 months. In addition to the two disease-defining features of spondylometaphyseal dysplasia and hypomyelination on MRI, common clinical signs and symptoms included motor deterioration, spasticity, tremor, ataxia, dysarthria, cognitive defects, pulmonary hypertension, nystagmus, and vision loss due to retinopathy. The course of the disease was slowly progressive. All patients had maternally inherited or de novo mutations in or near exon 7 of AIFM1, within a region of 70 bp, including synonymous and intronic changes. AIFM1 mutations have previously been associated with neurologic presentations as varied as intellectual disability, hearing loss, neuropathy, and striatal necrosis, while AIFM1 mutations in this small region present with a distinct phenotype implicating bone. Analysis of cell lines derived from four patients identified significant reductions in AIFM1 mRNA and protein levels in osteoblasts. We hypothesize that AIFM1 functions in bone metabolism and myelination and is responsible for the unique phenotype in this condition.</p

Phenotypic and molecular characterisation of CDK13-related congenital heart defects, dysmorphic facial features and intellectual developmental disorders

Background: De novo missense variants in CDK13 have been described as the cause of syndromic congenital heart defects in seven individuals ascertained from a large congenital cardiovascular malformations cohort. We aimed to further define the phenotypic and molecular spectrum of this newly described disorder. Methods: To minimise ascertainment bias, we recruited nine additional individuals with CDK13 pathogenic variants from clinical and research exome laboratory sequencing cohorts. Each individual underwent dysmorphology exam and comprehensive medical history review. Results: We demonstrate greater than expected phenotypic heterogeneity, including 33% (3/9) of individuals without structural heart disease on echocardiogram. There was a high penetrance for a unique constellation of facial dysmorphism and global developmental delay, as well as less frequently seen renal and sacral anomalies. Two individuals had novel CDK13 variants (p.Asn842Asp, p.Lys734Glu), while the remaining seven unrelated individuals had a recurrent, previously published p.Asn842Ser variant. Summary of all variants published to date demonstrates apparent restriction of pathogenic variants to the protein kinase domain with clustering in the ATP and magnesium binding sites. Conclusions: Here we provide detailed phenotypic and molecular characterisation of individuals with pathogenic variants in CDK13 and propose management guidelines based upon the estimated prevalence of anomalies identified. Keywords: CDK13, CHDFIDD, De novo variant, Neurodevelopmental disorders, Agenesis of the corpus callosum, Hypertelorism, Developmental delay, Cyclin-dependent kinase, Undiagnosed Diseases Networ

Nonlinear characterization of a bistable energy harvester dynamical system

International audienceThis chapter explores the nonlinear dynamics of a piezo-magneto-elastic bistable energy device system regards the influence of external forcing parameters influence on system response. Time series, Poincaré maps, phase space trajectories, and bifurcation diagrams are employed in order to reveals system dynamics complexity and nonlinear effects, such as chaos incidence and hysteresis

Crustal Azimuthal Anisotropy Beneath the Central North China Craton Revealed by Receiver Functions

To characterize crustal anisotropy beneath the central North China Craton (CNCC), we apply a recently developed deconvolution approach to effectively remove near-surface reverberations in the receiver functions recorded at 200 broadband seismic stations and subsequently determine the fast orientation and the magnitude of crustal azimuthal anisotropy by fitting the sinusoidal moveout of the P to S converted phases from the Moho and intracrustal discontinuities. The magnitude of crustal anisotropy is found to range from 0.06 s to 0.54Â s, with an average of 0.25 ± 0.08Â s. Fault-parallel anisotropy in the seismically active Zhangjiakou-Penglai Fault Zone is significant and could be related to fluid-filled fractures. Historical strong earthquakes mainly occurred in the fault zone segments with significant crustal anisotropy, suggesting that the measured crustal anisotropy is closely related to the degree of crustal deformation. The observed spatial distribution of crustal anisotropy suggests that the northwestern terminus of the fault zone probably ends at about 114°E. Also observed is a sharp contrast in the fast orientations between the western and eastern Yanshan Uplifts separated by the North-South Gravity Lineament. The NW-SE trending anisotropy in the western Yanshan Uplift is attributable to fossil crustal anisotropy due to lithospheric extension of the CNCC, while extensional fluid-saturated microcracks induced by regional compressive stress are responsible for the observed ENE-WSW trending anisotropy in the eastern Yanshan Uplift. Comparison of crustal anisotropy measurements and previously determined upper mantle anisotropy implies that the degree of crust-mantle coupling in the CNCC varies spatially

Premature Senescence and Increased TGFβ Signaling in the Absence of Tgif1

Transforming growth factor β (TGFβ) signaling regulates cell cycle progression in several cell types, primarily by inducing a G1 cell cycle arrest. Tgif1 is a transcriptional corepressor that limits TGFβ responsive gene expression. Here we demonstrate that primary mouse embryo fibroblasts (MEFs) lacking Tgif1 proliferate slowly, accumulate increased levels of DNA damage, and senesce prematurely. We also provide evidence that the effects of loss of Tgif1 on proliferation and senescence are not limited to primary cells. The increased DNA damage in Tgif1 null MEFs can be partially reversed by culturing cells at physiological oxygen levels, and growth in normoxic conditions also partially rescues the proliferation defect, suggesting that in the absence of Tgif1 primary MEFs are less able to cope with elevated levels of oxidative stress. Additionally, we show that Tgif1 null MEFs are more sensitive to TGFβ-mediated growth inhibition, and that treatment with a TGFβ receptor kinase inhibitor increases proliferation of Tgif1 null MEFs. Conversely, persistent treatment of wild type cells with low levels of TGFβ slows proliferation and induces senescence, suggesting that TGFβ signaling also contributes to cellular senescence. We suggest that in the absence of Tgif1, a persistent increase in TGFβ responsive transcription and a reduced ability to deal with hyperoxic stress result in premature senescence in primary MEFs

Examining the types and payments of the disabilities of the insurants in the national farmers' health insurance program in Taiwan

<p>Abstract</p> <p>Background</p> <p>In contrast to the considerable body of literature concerning the disabilities of the general population, little information exists pertaining to the disabilities of the farm population. Focusing on the disability issue to the insurants in the Farmers' Health Insurance (FHI) program in Taiwan, this paper examines the associations among socio-demographic characteristics, insured factors, and the introduction of the national health insurance program, as well as the types and payments of disabilities among the insurants.</p> <p>Methods</p> <p>A unique dataset containing 1,594,439 insurants in 2008 was used in this research. A logistic regression model was estimated for the likelihood of received disability payments. By focusing on the recipients, a disability payment and a disability type equation were estimated using the ordinary least squares method and a multinomial logistic model, respectively, to investigate the effects of the exogenous factors on their received payments and the likelihood of having different types of disabilities.</p> <p>Results</p> <p>Age and different job categories are significantly associated with the likelihood of receiving disability payments. Compared to those under age 45, the likelihood is higher among recipients aged 85 and above (the odds ratio is 8.04). Compared to hired workers, the odds ratios for self-employed and spouses of farm operators who were not members of farmers' associations are 0.97 and 0.85, respectively. In addition, older insurants are more likely to have eye problems; few differences in disability types are related to insured job categories.</p> <p>Conclusions</p> <p>Results indicate that older farmers are more likely to receive disability payments, but the likelihood is not much different among insurants of various job categories. Among all of the selected types of disability, a highest likelihood is found for eye disability. In addition, the introduction of the national health insurance program decreases the likelihood of receiving disability payments. The experience in Taiwan can be valuable for other countries that are in an initial stage to implement a universal health insurance program.</p

Clinical, neuroradiological, and molecular characterization of mitochondrial threonyl-tRNA-synthetase (TARS2)-related disorder

PURPOSE: Biallelic variants in TARS2, encoding the mitochondrial threonyl-tRNA-synthetase, have been reported in a small group of individuals displaying a neurodevelopmental phenotype, but with limited neuroradiological data and insufficient evidence for causality of the variants. METHODS: Exome or genome sequencing was carried out in 15 families. Clinical and neuroradiological evaluation was performed for all affected individuals, including review of 10 previously reported individuals. The pathogenicity of TARS2 variants was evaluated using in vitro assays, and a zebrafish model. RESULTS: We report 18 new individuals harboring biallelic TARS2 variants. Phenotypically, these individuals show developmental delay/intellectual disability, regression, cerebellar and cerebral atrophy, basal ganglia signal alterations, hypotonia, cerebellar signs and increased blood lactate. In vitro studies showed that variants within the TARS2301-381 region had decreased binding to Rag GTPases, likely impairing mTORC1 activity. The zebrafish model recapitulated key features of the human phenotype and unraveled dysregulation of downstream targets of mTORC1 signaling. Functional testing of the variants confirmed the pathogenicity in a zebrafish model. CONCLUSION: We define the clinico-radiological spectrum of TARS2-related mitochondrial disease, unveil the likely involvement of the mTORC1 signaling pathway as a distinct molecular mechanism, and establish a TARS2 zebrafish model as an important tool to study variant pathogenicity