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EUS-EMG revealed EUS bursting activity during voiding with clear active and silent phases in young rats but unclear active and silent phases in aged rats. Masson's trichrome staining of the urethra showed EUS atrophy in aged rats compared to young and middle-aged rats. TPX-0005 The results indicate that aging induces two urethral dysfunctions in the urethral smooth muscle and EUS, which may lead to dyscoordination between the urinary bladder and urethra.The circadian clock and metabolism are tightly intertwined. Hence, the specific timing of interventions that target metabolic changes may affect their efficacy. Here we retrospectively compared the metabolic health effects of morning versus afternoon exercise training in metabolically compromised subjects enrolled in a 12-week exercise training program. Thirty-two adult males (58 ± 7 yrs) at risk for or diagnosed with type 2 diabetes performed 12 weeks of supervised exercise training either in the morning (8.00-10.00 a.m., N = 12) or in the afternoon (3.00-6.00 p.m., N = 20). Compared to participants who trained in the morning, participants who trained in the afternoon experienced superior beneficial effects of exercise training on peripheral insulin sensitivity (+5.2 ± 6.4 vs. -0.5 ± 5.4 μmol/min/kgFFM, p = .03), insulin-mediated suppression of adipose tissue lipolysis (-4.5 ± 13.7% vs. +5.9 ± 11%, p = .04), fasting plasma glucose levels (-0.3 ± 1.0 vs. +0.5 ± 0.8 mmol/l, p = .02), exercise performance (+0.40 ± 0.2 vs. +0.2 ± 0.1 W/kg, p = .05) and fat mass (-1.2 ± 1.3 vs. -0.2 ± 1.0 kg, p = .03). In addition, exercise training in the afternoon also tended to elicit superior effects on basal hepatic glucose output (p = .057). Our findings suggest that metabolically compromised subjects may reap more pronounced metabolic benefits from exercise training when this training is performed in the afternoon versus morning. CLINICALTRIALS.GOV ID NCT01317576.

The aim of this study was to develop a self-assessment tool, the Role Performance Scale for Middle-aged Generalist Nurses in Japan and confirm its reliability and validity.

Scale items were extracted from interviews, and item and scale-level validity were rated by nursing management researchers and middle-aged generalist nurses. The resulting 36-item questionnaire was administered to clinical generalist nurses (middle-aged nurses, n = 837; young nurses, n = 800) in Japan. Exploratory and confirmatory factor analyses were performed, and the tool's internal consistency and construct validity were analyzed.

Valid responses obtained from 504 middle-aged and 311 young generalist nurses were included in the analysis. The final scale was composed of 25 items, which were divided into five factors "backing up head nurses," "instructing young nurses on practices as an informal mentor," "providing young nurses with mental support," "providing empathic support to patients and their families," and "coordinating team medical care." In the confirmatory factor analysis, the indices of fitness supported these results. The Cronbach's alpha coefficient was .94 for the total scale and ranged from .72 to .91 for the five factors. The five factors explained a cumulative variance of 65.4%.

The five-factor, 25-item Role Performance Scale for Middle-aged Generalist Nurses in Japan was confirmed to have sufficient reliability and validity. link2 Middle-aged generalist nurses can use this tool to self-assess their nursing behavior. In addition, head nurses can use it to assess the role performance of middle-aged generalist nurses and aid in their continual education.

The five-factor, 25-item Role Performance Scale for Middle-aged Generalist Nurses in Japan was confirmed to have sufficient reliability and validity. Middle-aged generalist nurses can use this tool to self-assess their nursing behavior. In addition, head nurses can use it to assess the role performance of middle-aged generalist nurses and aid in their continual education.The low rate of durable response against relapsed and/or refractory multiple myeloma (RRMM) in recent studies indicates that chimeric antigen receptor T-cell (CART) treatment is yet to be optimized. This study aims to investigate the safety and efficacy of sequential infusion of CD19-CART and B-cell maturation antigen (BCMA)-CARTs for RRMM with a similar 3 + 3 dose escalation combined with a toxicity sentinel design. We enrolled 10 patients, among whom 7 received autologous infusion and 3 received allogeneic infusion. The median follow-up time was 20 months. The most common grade 3/4 treatment-emergent toxicities were hematological toxicities. Cytokine-release syndrome (CRS) adverse reactions were grade 1/2 in 9 out of 10 subjects. No dose-limited toxicity (DLT) was observed for BCMA-CAR-positive T cells ≤5 × 107 /kg), while two patients with dose-levels of 5-6.5 × 107 /kg experienced DLTs. The overall response rate was 90% (five partial responses and four stringent complete responses). Three out of four patients with stringent complete responses to autologous CART had progression-free survival for over 2 years. The three patients with allogeneic CART experienced disease progression within 2 months. These results evidence the sequential infusion's preliminarily tolerability and efficacy in RRMM, and present a simple and safe design applicable for the establishment of multiple CART therapy.At present, it is a considerable challenge to mimic the complex architecture of osteochondral (OC) tissue. In this study, a porous and gradient mineralized double-network hydrogel is synthesized and used to induce bone marrow mesenchymal stem cells (BMSCs) to differentiate into the desired OC tissue depending only on the material and mechanical properties. Physical and chemical characterizations show that hydroxyapatite nanoparticles grow and fill into the pores of the hydrogel, and their content presents a gradient change in different layers of hydrogel. The synthesized hydrogel has excellent mechanical properties and the compression strength with different mineralization degrees varies from 27 to 380 kPa, which fully meets the needs of increased mechanical strength of articular cartilage from the surface to the deep layer. Besides, the synthesized hydrogel has good biocompatibility that can promote the proliferation and growth of BMSCs. More importantly, the results of histochemistry, immunohistochemistry, and real time polymerase chain reaction show that gradient mineralized hydrogel can induce BMSCs to differentiate into the desired chondrocytes and osteoblasts in different layers of hydrogels, indicating that OC tissues can be successfully constructed through a simple induction differentiation of gradient mineralized hydrogel.Black individuals exhibit increased blood pressure (BP) responses to sympathetic stimulation that are associated with an increased risk of hypertension (HTN). We tested the hypothesis that α1 -adrenergic blockade inhibits the increased BP response during and after 45-min stress in young normotensive Black adults, which may be mediated, in part, by dampened vasoconstriction and decreased renal sodium retention. Utilizing a double-masked randomized, crossover study design, 51 normotensive Black adults (31 ± 8 yr) were treated with either a placebo or 1 mg/day of prazosin for 1 week. link3 On the final day of each treatment, hemodynamic measures and urinary sodium excretion (UNaV) were collected before (Rest), during (Stress) and after (Recovery) 45 min of mental stress induced via a competitive video game task. During the Stress period, diastolic BP and total peripheral resistance (TPR) were significantly lower with prazosin compared to placebo (p less then .05 for both). Similarly, we observed lower systolic BP, diastolic BP, and TPR during the Recovery period with prazosin versus placebo (p less then .05 for both). There was no effect of prazosin on stress-associated UNaV. The change in systolic BP from Rest to Recovery was positively associated with the change in TPR with both treatments (p less then .05 for both). In summary, prazosin treatment dampened BP reactivity to 45-min mental stress and lowered post-stress BP over the recovery period, which was linked to reduce TPR in young normotensive Black adults. These results suggest that α1 -adrenergic receptor activity may contribute to BP responses and delayed BP recovery to prolonged mental stress through increased vasoconstriction in Black adults.Hypoxia-inducible factor 1α (HIF-1α) is a transcription factor mediating adaptive responses to hypoxia and ischemia. Our previous work showed that HIF-1α is increased in muscle sensory nerves of rats with peripheral artery disease (PAD) induced by femoral artery occlusion. The present study was further to examine the role played by HIF-1α in regulating the response of arterial blood pressure (BP) to the activation of muscle afferent nerve during static muscle contraction in rats with femoral artery occlusion. A rat model of femoral artery ligation was used to study PAD in this study. Western blot analysis was employed to examine the protein levels of HIF-1α in the dorsal root ganglion (DRG) tissues. BAY87, a synthesized compound with the characteristics of highly potent and specific suppressive effects on expression and activity of HIF-1α, was given into the arterial blood supply of the ischemic hindlimb muscles before the exercise pressor reflex was evoked by static muscle contraction. First, HIF-1α was increased in the DRG of occluded limbs (optical density 0.89 ± 0.13 in control versus 1.5 ± 0.05 in occlusion; p 0.05, n = 5 in each group). In addition, muscle contraction evoked a greater increase in BP in occluded rats. BAY87 attenuated the enhanced BP response in occluded rats to a greater degree than in control rats. Our data suggest that the inhibition of HIF-1α alleviates the exaggeration of the exercise pressor reflex in rats under ischemic circumstances of the hindlimbs in PAD induced by femoral artery occlusion.

To assess the correlation of WHO histological classification and Masaoka-Koga staging system of thymic epithelial tumors (TETs) with prognosis.

We retrospectively analyzed 83 patients with TETs in the Instituto Nacional de Enfermedades Neoplasicas between 1996 to 2018. We analyzed the clinical stages, histological types and treatment modalities and attempted to determine the impact on overall survival. The data was retrieved from clinical files and reviewed by a pathologist who reclassificated according to the 2004 WHO classification system. The staging was performed with the Masaoka-Koga staging system. Survival curves were constructed with Kaplan-Meir method.

There was a total of 83 patients with a median age of 55 years old included in the study. The histological type corresponded to thymoma (T) in 63.8% (n = 53) and to thymic carcinoma (TC) in 36.1%. T were type A, AB, B1, B2 and B3 in 14.4%, 18%, 12%, 3.6%, 7.4% of cases, respectively. The proportion of advanced disease (Masaoka stage III-IV) was high (65%). With a median follow-up of 88.4 months, median overall survival (OS) was 81.6 months for T and 12.3 months for TC (P = 0.01). Univariate analysis showed that sex, histological type, clinical stage and surgery (P = 0.01) were significant independent prognostic factors. On multivariate analysis, histology type and Masaoka-Koga staging had an effect on survival.

The results indicates a clear association between the WHO histological classification and Masaoka-Koga staging system with survival. We found a higher proportion of TETs with advanced disease at diagnosis. Further research are required and collaboration is important to foster knowledge focused on classification and treatment.

SIGNIFICANT FINDINGS OF THE STUDY The WHO histological classification, the Masaoka-Koga system and surgery treatment were associated with overall survival.

To determine prognosis factors in TETs.

To determine prognosis factors in TETs.

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