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39-4.56). We observed no association between any of the other investigated contaminants and IPF mortality or severity.
Air pollution, specifically that caused by carbon monoxide, can increase mortality in patients with IPF.
Air pollution, specifically that caused by carbon monoxide, can increase mortality in patients with IPF.
Patient-reported outcome measures have become an important part of routine care. The aim of this study was to determine if Patient-Reported Outcomes Measurement Information System (PROMIS) measures can be used to create patient subgroups for individuals seeking orthopaedic care.
This was a cross-sectional study of patients from Duke University Department of Orthopaedic Surgery clinics (14 ambulatory and four hospital-based). Ipatasertib molecular weight There were two separate cohorts recruited by convenience sampling (i.e. patients were included in the analysis only if they completed PROMIS measures during a new patient visit). Cohort #1 (n = 12,141; December 2017 to December 2018,) included PROMIS short forms for eight domains (Physical Function, Pain Interference, Pain Intensity, Depression, Anxiety, Sleep Quality, Participation in Social Roles, and Fatigue) and Cohort #2 (n = 4,638; January 2019 to August 2019) included PROMIS Computer Adaptive Testing instruments for four domains (Physical Function, Pain Interference, Depressionbgroups have prognostic validity. Cite this article
2021;2(7)493-502.
These findings suggest orthopaedic patient subgroups differing in physical function, pain, and psychosocial distress can be created from as few as four different PROMIS measures. Longitudinal research is necessary to determine whether these subgroups have prognostic validity. Cite this article Bone Jt Open 2021;2(7)493-502.Autosomal dominant tubulointerstitial kidney disease (ADTKD)-uromodulin (UMOD) is the most common nonpolycystic genetic kidney disease, but it remains unrecognized due to its clinical heterogeneity and lack of screening test. Moreover, the fact that the clinical feature is a poor predictor of disease outcome further highlights the need for the development of mechanistic biomarkers in ADTKD. However, low abundant urinary proteins secreted by thick ascending limb cells, where UMOD is synthesized, have posed a challenge for the detection of biomarkers in ADTKD-UMOD. In the CRISPR/Cas9-generated murine model and patients with ADTKD-UMOD, we found that immunoglobulin heavy chain-binding protein (BiP), an endoplasmic reticulum chaperone, was exclusively upregulated by mutant UMOD in the thick ascending limb and easily detected by Western blot analysis in the urine at an early stage of disease. However, even the most sensitive ELISA failed to detect urinary BiP in affected individuals. We therefore developed an ultreticulum stress biomarker in ADTKD-UMOD, which will be valuable in monitoring disease progression and the treatment response in ADTKD.Primary cilia are widely regarded as specialized sensors in differentiated cells that have been implicated in the regulation of cell proliferation, differentiation, and viability. We have previously shown that shortening of primary cilia sensitizes cultured kidney tubular cells to cisplatin-induced apoptosis. Intraflagellar transport 88 (IFT88) is an essential component for ciliogenesis and maintenance. Here, we have further examined the effect of proximal tubule-specific IFT88 ablation on cisplatin-induced acute kidney injury (AKI). In this study, more severe AKI occurred in IFT88 knockout mice than age- and sex-matched wild-type mice. Mechanistically, cisplatin stimulated autophagy in kidney tubular cells as an intrinsic protective mechanism. However, renal autophagy was severely impaired in IFT88 knockout mice. In cultured HK-2 cells, cisplatin induced more apoptosis when IFT88 was knocked down. Tat-beclin 1 peptide, a specific autophagy activator, could partially prevent IFT88-associated cell death during cisplatin treatment, although cilium length was not improved significantly. Reexpression of IFT88 partially restored autophagy in IFT88 knockdown cells and suppressed apoptosis during cisplatin treatment. Taken together, these results indicate that defective autophagy in IFT88-deficient kidney cells and tissues contributes to the exaggerated AKI following cisplatin exposure.NEW & NOTEWORTHY Almost every cell has one hair-like, nonmotile antenna projecting from the cell surface, named the primary cilium. In kidney tubular cells, the primary cilium has a protective role, but the underlying mechanism is unclear. This study shows that a short cilium leads to the suppression of autophagy, which is responsible for the heightened injury sensitivity. These findings provide the clues of how to manipulate primary cilium and autophagy to save kidneys.The epithelial Na+ channel (ENaC) constitutes the rate-limiting step for Na+ absorption in the aldosterone-sensitive distal nephron (ASDN) comprising the late distal convoluted tubule (DCT2), connecting tubule (CNT), and collecting duct (CD). Previously, we demonstrated that ENaC activity in the DCT2/CNT transition zone is constitutively high and independent of aldosterone, in contrast to its aldosterone dependence in the late CNT/initial cortical CD (CCD). The mineralocorticoid receptor (MR) is expressed in the entire ASDN. Its activation by glucocorticoids is prevented through 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) abundantly expressed in the late but probably not early part of the ASDN. We hypothesized that ENaC function in the early part of the ASDN is aldosterone independent but may depend on MR activated by glucocorticoids due to low 11β-HSD2 abundance. To test this hypothesis, we used doxycycline-inducible nephron-specific MR-deficient [MR knockout (KO)] mice. Whole cell ENaC currents were invesT. Furthermore, we demonstrated that cells of this latter nephron segment express little 11β-HSD2, which probably allows glucocorticoids to stimulate MR, resulting in aldosterone-independent ENaC activity in DCT2/CNT. This site-specific ENaC regulation has physiologically relevant implications for renal sodium and potassium homeostasis.Background Clinically, corticosteroids are used mainly for their immune-modulatory properties but are also known to influence mood. Despite evidence of a role in regulating tryptophan hydroxylases (TPH), key enzymes in serotonin biosynthesis, a direct action of corticosteroids on these enzymes has not been systematically investigated. Methodology & results Corticosteroid effects on TPHs were tested using an in vitro assay. The compound with the strongest modulatory effect, beclomethasone dipropionate, activated TPH1 and TPH2 with low micromolar potency. Thermostability assays suggested a stabilizing mechanism, and computational docking indicated that beclomethasone dipropionate interacts with the TPH active site. Conclusion Beclomethasone dipropionate is a stabilizer of TPHs, acting as a pharmacological chaperone. Our findings may inspire further development of steroid scaffolds as putative antidepressant drugs.
to describe an evaluation of interobserver agreement in the use of a checklist related to the use of nasoenteral tube (NSS) as a presupposition for quality in obtaining data.
a methodological study conducted in 2018 in a Brazilian hospital, preceding the data collection of an open-label clinical trial. Independent observers, blinded to the evaluation of their peers, evaluated patients with NSS through a 25-item checklist. The data collected by eight previously trained research assistants (RA) were compared to those obtained by an experienced nurse (reference standard). Agreement was measured using the kappa coefficient and PABAK.
a total of 451 observations were made in pairs. Considering the total items on the checklist there was almost perfect agreement (k > 0.80) in all observation pairs (nurse vs. each RA) RA 1 (k = 0.91; 95 % CI = 0.89-0.93); RA 2 (k = 0.83; 95 % CI = 0.80-0.85); AP 3 (k = 0.92; 95 % CI = 0.90-0.94); RA 4 (k = 0.83; 95 % CI = 0.80-0.86); RA 5 (k = 0.94; 95 % CI = 0.92-0.96); RA 6 (k = 0.94; 95 % CI = 0.92-0.96); RA 7 (k = 0.96; 95 % CI = 0.95-0.98); RA 8 (k = 0.73; 95 % CI = 0.70-0.77). However, for isolated items, and in specific RAs, there were fair agreements, unacceptable to effectively collect data from a clinical trial. Retraining and supervision of RAs were able to improve agreement between observers.
an evaluation of interobserver agreement proved to be fundamental to ensure the reliability of data collection and, therefore, to avoid measurement biases.
an evaluation of interobserver agreement proved to be fundamental to ensure the reliability of data collection and, therefore, to avoid measurement biases.In this paper, a simple chaotic memristor-based circuit with an external stimulation is proposed, and its basic dynamic properties are demonstrated. When the external perturbation becomes time varying and its frequency is low enough, the system has two-time scales, which can be employed to explore the mechanisms of symmetrical Hopf-induced bursting oscillations and delay effects. Furthermore, delay-times on Hopf-induced bursting at different frequencies of the external stimulation are measured. The results show that the relationship between the delay-time and external frequency is subject to a power law. In order to enhance the existing chaos of the system, a 4D system is developed by adding a nonlinear state feedback controller, which shows hyperchaos under some suitable parameters. These two systems are implemented on Multisim and hardware platforms, and the corresponding experimental results verify the correctness of the numerical simulations.The output signals of neurons that are exposed to external stimuli are of great importance for brain functionality. Traditional time-series analysis methods have provided encouraging results; however, the associated patterns and their correlations in the output signals of neurons are masked by statistical procedures. Here, graphlets are employed to extract the local temporal patterns and the transitions between them from the output signals when neurons are exposed to external stimuli with selected stimulating periods. A transition network is defined where the node is the graphlet and the direct link is the transition between two successive graphlets. The transition-network structure is affected by the simulating periods. When the stimulating period moves close to an integer multiple of the neuronal intrinsic period, only the backbone or core survives, while the other linkages disappear. Interestingly, the size of the backbone (number of nodes) equals the multiple. The transition-network structure is conservative within each stimulating region, which is defined as the range between two successive integer multiples. Nevertheless, the backbone or detailed structure is significantly altered between different stimulating regions. This alternation is induced primarily from a total of 12 active linkages. Hence, the transition network shows the structure of cross correlations in the output time-series for a single neuron.The standard model of visual search dynamics is Brownian motion. However, recent research in cognitive science reveals that standard diffusion processes seem not to be the appropriate models of human looking behavior. In particular, experimental results confirm that the superdiffusive Lévy-type dynamics appears in this context. In this paper, we analyze the diffusive properties of human eye movement in a language comprehension task. We propose a model that is a combination of a Markov chain with a finite number of states and a Lévy walk. Our model fits well the experimental data and allows one to investigate the properties of the visual search dynamics using numerical simulations.
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