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17, CI 95% 1.18-22.67, p=0.029), and greater deterioration of pFVC defined as decrement of last available pFVC compared to first available pFVC of ≥10% (HR 3.65, CI 95% 1.07-12.38, p=0.038).

Anti-Ro/SS-A antibody is an independent risk factor for worse pulmonary outcome and higher all-cause mortality in patients with SSc, independent of SSc clinical and/or serological subtype.

Anti-Ro/SS-A antibody is an independent risk factor for worse pulmonary outcome and higher all-cause mortality in patients with SSc, independent of SSc clinical and/or serological subtype.

UK Biobank (UKB) is a large prospective cohort capturing numerous health outcomes, but limited occupational information (job title, self-reported manual work and occupational walking/standing).

To create and evaluate validity of a linkage between UKB and a job exposure matrix for physical work exposures based on the US Occupational Information Network (O*NET) database.

Job titles and UK Standard Occupational Classification (SOC) codes were collected during UKB baseline assessment visits. Using existing crosswalks, UK SOC codes were mapped to US SOC codes allowing linkage to O*NET variables capturing numerous dimensions of physical work. Job titles with the highest O*NET scores were assessed to evaluate face validity. Spearman's correlation coefficients were calculated to compare O*NET scores to self-reported UKB measures.

Among 324 114 participants reporting job titles, 323 936 were linked to O*NET. Expected relationships between scores and self-reported measures were observed. For static strength (0-7 scale), the median O*NET score was 1.0 (e.g. audiologists), with a highest score of 4.88 for stone masons and a positive correlation with self-reported heavy manual work (Spearman's coefficient = 0.50). For time spent standing (1-5 scale), the median O*NET score was 2.72 with a highest score of 5 for cooks and a positive correlation with self-reported occupational walking/standing (Spearman's coefficient = 0.56).

While most jobs were not physically demanding, a wide range of physical work values were assigned to a diverse set of jobs. This novel linkage of a job exposure matrix to UKB provides a potentially valuable tool for understanding relationships between occupational exposures and disease.

While most jobs were not physically demanding, a wide range of physical work values were assigned to a diverse set of jobs. This novel linkage of a job exposure matrix to UKB provides a potentially valuable tool for understanding relationships between occupational exposures and disease.CANVAS caused by RFC1 biallelic expansions is a major cause of inherited sensory neuronopathy. Detection of RFC1 expansion is challenging and CANVAS can be associated with atypical features. We clinically and genetically characterized 50 patients, selected based on the presence of sensory neuronopathy confirmed by EMG. We screened RFC1 expansion by PCR, repeat-primed PCR, and Southern blotting of long-range PCR products, a newly developed method. Neuropathological characterization was performed on the brain and spinal cord of one patient. Most patients (88%) carried a biallelic (AAGGG)n expansion in RFC1. In addition to the core CANVAS phenotype (sensory neuronopathy, cerebellar syndrome, and vestibular impairment), we observed chronic cough (97%), oculomotor signs (85%), motor neuron involvement (55%), dysautonomia (50%), and parkinsonism (10%). Motor neuron involvement was found for 24 of 38 patients (63.1%). First motor neuron signs, such as brisk reflexes, extensor plantar responses, and/or spasticity, weted, with widespread Lewy bodies in the locus coeruleus, substantia nigra, hippocampus, entorhinal cortex, and amygdala. We propose new guidelines for the screening of RFC1 expansion, considering different expansion motifs. Here, we developed a new method to more easily detect pathogenic RFC1 expansions. We report frequent motor neuron involvement and different neuronopathy subtypes. Parkinsonism was more prevalent in this cohort than in the general population, 10% versus the expected 1% (p  less then  0.001). We describe, for the first time, the spinal cord pathology in CANVAS, showing the alteration of posterior columns and roots, astrocytic gliosis and axonal swelling, suggesting motor neuron synaptic dysfunction.This study aimed to assess the clinical outcomes of linear accelerators (linac)-based, stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator for brain metastasis in the primary motor cortex (BMPMC). Thirty-five consecutive patients with BMPMC who were treated by linac-based SRS or fSRT between January 2012 and March 2020 were analyzed. BMPMC was defined as a tumor located in the precentral gyrus on gadolinium-enhanced magnetic resonance imaging (MRI) and T2-weghted imaging (T2WI). In total, 35 patients with 37 metastases were analyzed. The median follow-up time was 13 (range 1-97) months. The tumor volume was 0.05-26.5 (median 0.62) cm3. All patients were treated with SRS or fSRT using 35 Gy with 7 Gy per fraction daily. The median survival time (MST) was 16.9 months. The pretreatment KPS and RPA class significantly differed in terms of MST on the log-rank tests. Seven symptomatic patients had hemiparesis before SRS or fSRT. All symptomatic patients, except one with facial paresis and one who died within 3 months, experienced improvement at a 3 month follow-up. None of the patients presented with persistent radiation injury at the final follow-up. Two patients presented with grade 3 radiation-related central nervous system necrosis, which was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. In BMPMC, SRS and fSRT had good tumor control and did not cause serious complications. Therefore, they are suitable treatment options with an acceptable safety profile.Two highly prevalent pulmonary diseases, lung cancer and chronic obstructive lung disease (COPD), show both sex and gender differences in their presentations and outcomes. Sex differences are defined as biological differences associated with the male vs female genotype, and gender differences are defined as behavioral or social differences that primarily arise because of gender identity. The incidence of both lung cancer and COPD has increased dramatically in women over the past 50 years, and both are associated with chronic pulmonary inflammation. Development of COPD is also a risk factor for lung cancer. In this review, the main differences in lung cancer and COPD biology observed between men and women will be summarized. Potential causative factors will be discussed, including the role of estrogen in promoting pro-growth and inflammatory phenotypes which may contribute to development of both lung cancer and COPD. Response of the innate and adaptive immune system to estrogen is a likely factor in the biology of both lung cancer and COPD. Estrogen available from synthesis by reproductive organs as well as local pulmonary estrogen synthesis may be involved in activating estrogen receptors expressed by multiple cell types in the lung. Estrogenic actions, although more pronounced in women, may also have importance in the biology of lung cancer and COPD in men. Effects of estrogen are also timing and context dependent; the multiple cell types that mediate estrogen action in the lungs may confer both positive and negative effects on disease processes.Multiple oviposition attractants are used for Culex (Diptera Culicidae) mosquito surveillance in the CDC Gravid Trap, including hay and fish emulsion-infused water. Despite the use of both in the United States, no research has compared their attractiveness. We conducted trapping throughout Louisiana to assess the attractiveness of hay and fish emulsion-infused water in various habitat types and climates. Our results indicate that fish emulsion-infused water attracts more mosquitoes overall, more Culex quinquefasciatus (Say, 1823), and a wider diversity of mosquitoes than hay-infused water. This trend was maintained, regardless of habitat type or climate.Protein homeostasis (proteostasis) is a prerequisite for cellular viability and plasticity. In particular, post-mitotic cells such as neurons rely on a tightly regulated safeguard system that allows for regulated protein expression. Previous investigations have identified RNA-binding proteins (RBPs) as crucial regulators of protein expression in nerve cells. However, during neurodegeneration, their ability to control the proteome is progressively disrupted. In this review, we examine the malfunction of key RBPs such as TAR DNA-binding protein 43 (TDP-43), Fused in Sarcoma (FUS), Staufen, Pumilio and fragile-X mental retardation protein (FMRP). Therefore, we focus on two key aspects of RBP dysfunctions in neurodegeneration protein aggregation and dysregulation of their target RNAs. Moreover, we discuss how the chaperone system responds to changes in the RBP-controlled transcriptome. Based on recent findings, we propose a two-hit model in which both, harmful RBP deposits and target mRNA mistranslation contribute to neurodegeneration observed in RBPathologies.Diffusely abnormal white matter (DAWM), characterised by biochemical changes of myelin in the absence of frank demyelination, has been associated with clinical progression in secondary progressive MS (SPMS). However, little is known about changes of DAWM over time and their relation to focal white matter lesions (FWML). The objectives of this work were 1) To characterize the longitudinal evolution of FWML, DAWM, and DAWM that transforms into FWML, and 2) To determine whether gadolinium enhancement, known to be associated with the development of new FWML, is also related to DAWM voxels that transform into FWML. Our data included 4220 MRI scans of 689 SPMS participants, followed for 156 weeks and 2677 scans of 686 RRMS participants, followed for 96 weeks. Selleck Proteasome inhibitor FWML and DAWM were segmented using a previously validated, automatic thresholding technique based on normalized T2 intensity values. Using longitudinally registered images, DAWM voxels at each visit that transformed into FWML on the last MRI scan as well as thal inflammation and gadolinium enhancement.The dose rate of atomic bomb (A-bomb) radiation to the survivors has still remained unclear, although the dose-response data of A-bomb cancers has been taken as a standard in estimating the cancer risk of radiation and the dose and dose-rate effectiveness factor (DDREF). Since the applicability of the currently used DDREF of 2 derived from A-bomb data is limited in a narrow dose-rate range, 0.25-75 Gy/min as estimated from analysis of DS86 dosimetry data in the present study, a non-tumor dose (Dnt) was applied in an attempt to gain a more universal dose-rate effectiveness factor (DREF), where Dnt is an empirical parameter defined as the highest dose at which no statistically significant tumor increase is observed above the control level and its magnitude depends on the dose rate. The new DREF values were expressed as a function of the dose rate at four exposure categories, i.e. partial body low LET, whole body low linear energy transfer (LET), partial body high LET and whole body high LET and provided a value of 14 for environmental level radiation at a dose rate of 10-9 Gy/min for whole body low LET.

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