Validity evidence for simulator-based obstetric ultrasound competency assessment tool: a multi-center study.

PURPOSE: To collect validity evidence for a simulator-based obstetric ultrasound competency assessment tool (OUCAT). METHODS: 89 sonographers from three centers (XY, MC, DT), including novices (n=21), experienced trainees (n=44), and experts (n=24), participated in the competency assessment. Validity evidence of OUCAT was collected according to Standards for Educational and Psychological Testing. Content validity was ensured by reviewing guidelines and reaching expert consensus. The response process was ensured via training raters. Internal structure was explored through internal consistency, inter-rater reliability, and test-retest reliability. Relations to other variables were explored by comparing OUCAT scores of sonographers with different experience. Evidence for consequences was collected by determining the pass/fail level. RESULTS: OUCAT included 123 items, of which 117 items could effectively distinguish novices from experts (P<0.05). The internal consistency was represented by the Cronbach's α coefficient (0.978). The inter-rater reliability was high, with XY being 0.868, MC being 0.877, and DT being 0.937 (P<0.001). Test-retest reliability was 0.732 (P=0.001). The performance of experts was significantly better than experienced trainees, and the performance of experienced trainees was significantly better than novices (70.3±10.7 vs. 39.8±15.0 vs. 20.5±10.6, P<0.001). The pass/fail level determined by contrast group method was 45 points. The passing rate of novices, experienced trainees and experts was 0% (0/21), 31.8% (14/44), and 100% (24/24), respectively. CONCLUSION: Simulator-based OUCAT exhibits good reliability and validity in assessing obstetric ultrasound skills.

Initial treatment with a single capsule containing half-dose quadruple therapy vs standard-dose dual therapy in hypertensive patients (QUADUAL): Study protocol for a randomized, blinded, crossover trial.

BACKGROUND: Combined antihypertensive therapy has obvious advantages over single drug therapy. Hypertension guidelines fully affirm the efficacy of dual combination in initial antihypertensive therapy. Recent studies have also pointed out that the quadruple combination of very low-dose antihypertensive drugs is superior to single drugs. However, whether low-dose quadruple therapy is better than dual combination is unknown. OBJECTIVE: To evaluate and compare the efficacy and safety of half-dose quadruple therapy vs standard-dose dual therapy in the initial treatment of hypertensive patients with systolic/diastolic blood pressure 140-179/90-109 mm Hg. METHODS: A randomized double-blind crossover clinical trial will be conducted to compare the efficacy and safety of low-dose quadruple antihypertensives (irbesartan 75 mg + metoprolol 23.75 mg + amlodipine 2.5 mg + indapamide 1.25 mg) with standard-dose dual antihypertensives (irbesartan 150 mg + amlodipine 5 mg) in the initial treatment of patients with mild to moderate hypertension (140-179/90-109 mm Hg). Ninety patients are required and will be recruited and randomly assigned in a 1:1 ratio to 2 crossover groups. Two groups will receive a different combination therapy for 4 weeks, then switch to the other combination therapy for 4 weeks, with a 2-week wash-out. The patients will be followed up for 4 weeks to compare the antihypertensive effects and related adverse effects of the 2 antihypertensive combination treatments. CONCLUSIONS: We present the rationale for the design of the QUADUAL trial. The trial started in July 2022 and is expected to be completed by August 2023. The study aims to evaluate if an initial treatment regimen of quadruple combination of half-dose blood pressure medications will result in greater reduction in blood pressure and fewer side effects compared to standard dose dual therapy. REGISTRATION: www. CLINICALTRIALS: gov (NCT05377203).

2-BFI Provides Neuroprotection Against Fluorosis by Stabilizing Endoplasmic Reticulum-Mitochondria Contact Sites and Inhibiting Activation of the NLRP3 Inflammasome.

2-(2-benzofu-ranyl)-2-imidazoline (2-BFI) is a drug that has attracted much attention in recent years. It has a therapeutic effect on brain diseases in animal models such as Alzheimer's disease and cerebral infarction. However, whether 2-BFI affords neuroprotection against the toxicity of fluoride, which can cross the blood-brain barrier and cause neurological dysfunction is not known. We investigated the cell viability and apoptosis of SH-SY5Y cells and primary cultures of cortical neurons exposed to fluoride, and 2-BFI was used to protect both two kinds of cells against the effects of fluoride. We found that 2-BFI can provide neuroprotection on SH-SY5Y cells and primary cultures of cortical neurons upon fluorosis by maintaining the stability of endoplasmic reticulum-mitochondria contact sites and inhibiting activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome. This study may provide a new method for protecting against the neurotoxicity induced by fluoride exposure.

Correlation of lipoprotein-associated phospholipase A2 and cerebral microbleeds in patients with acute ischaemic stroke.

BACKGROUND AND AIMS: Cerebral microbleeds (CMBs) increase the risk of stroke occurrence and recurrence,and affect the prognosis of stroke patients. Therefore, identifying biological markers that predict CMBs after stroke is urgently needed. This study explored whether high levels of lipoprotein-associated phospholipase A2(Lp-PLA2) are associated with an increased risk of CMBs in patients with acute ischaemic stroke (AIS). METHODS: From April 2020 to October 2021, we enrolled 242 patients with AIS. At admission, the plasma levels of Lp-PLA2 were measured in all patients as well as the number of CMBs and white matter lesions. According to the results of the Susceptibility Weighted Imaging (SWI), the patients were divided into a CMB group and a no-CMB group. The groups were compared with univariate and multivariate analyses to clarify the correlation between Lp-PLA2 levels and CMBs, and the optimal cut-off value of Lp-PLA2 that predicted CMBs was determined from the receiver-operating characteristic curve. RESULTS: CMBs were detected in 71 (29.3%) of the 242 AIS patients. The median Lp-PLA2 level was 182.79 ng/ml. Using the 1st quartile of Lp-PLA2 levels (the lowest levels) as the reference group, univariate logistic regression analysis showed that individuals in the 4th quartile (the highest levels) had a higher risk of CMBs (odds ratio [OR] = 1.460, 95% confidence interval [CI]: 1.188-1.795, P = 0.000). This correlation persisted after adjusting for relevant risk factors (OR = 1.370, 95% CI: 1.096-1.713, P = 0.006). The optimal cut-off value of Lp-PLA2 that predicted the occurrence of CMBs was 184.36 ng/ml; at this threshold, the sensitivity was 69.0%, and the specificity was 60.2%. CONCLUSIONS: Our data suggest that a high level of Lp-PLA2 in patients with AIS is a potential risk factor for CMBs.

Acute hypoxia promotes the liver angiogenesis of largemouth bass (Micropterus salmoides) by HIF - Dependent pathway.

A 24-h hypoxia exposure experiment was conducted to determine how hypoxia exposure induce liver angiogenesis in largemouth bass. Nitrogen (N2) was pumped into water to exclude dissolved oxygen into 1.2 ± 0.2 mg/L, and liver tissues were sampled during hypoxia exposure of 0 h, 4 h, 8 h, 12 h, 24 h and re-oxygenation for 12 h. Firstly, the results showed that hypoxia exposure promoted the angiogenesis occurrence by immunohistochemical analysis of vascular endothelial growth factor receptor 2 (VEGFR2). Secondly, the concentration of vasodilation factor increased and it's activity was elevated during 8 h exposure, such as nitric oxide (NO) and nitric oxide synthase (NOS) (p < 0.05). Thirdly, hypoxia exposure promoted angiogenesis through up-regulation the expression of matrix metalloproteinase 2 (MMP-2), jagged, protein kinase B (AKT), phosphoinositide-3-kinase (PI3K), mitogen-activated protein kinase (MAPK) at 4 h; contrarily, the expression of inhibiting angiogenesis genes presented up-regulated at 8 h (p < 0.05), such as matrix metalloproteinase inhibitor-2 (TIMP-2), matrix metalloproteinase inhibitor-3 (TIMP-3). Finally, the genes and proteins that regulate angiogenesis presented obvious chronological order. Parts of them promoted the budding and extension of blood vessels were up-regulated during 4 h-8 h (p < 0.05), such as vascular endothelial growth factor a (VEGFA), VEGFR2, monocarboxylic acid transporter 1 (MCT1), CD147, prolyl hydroxylase (PHD), nuclear factor kappa-B (NF-κB); other part of them promoted blood vessel maturation were highly expressed during 12 h-24 h (p < 0.05), such as angiogenin-1 (Ang-1) and angiogenin-2 (Ang-2). In short, acute hypoxia can promote the liver angiogenesis of largemouth bass by HIF - dependent pathway.

Comparison of two teaching methods for stopping the bleed: a randomized controlled trial.

BACKGROUND: The "Stop the Bleed" (STB) campaign has achieved remarkable results since it was launched in 2016, but there is no report on the teaching of an STB course combined with a trauma patient simulator. This study proposes the "problem-, team-, and evidence-based learning" (PTEBL) teaching method combined with Caesar (a trauma patient simulator) based on the STB course and compares its effect to that of the traditional teaching method among outstanding doctoral candidates training in haemostasis skills. METHOD: Seventy-eight outstanding doctoral candidate program students in five and eight-year programs were selected as the research subjects and were randomly divided into a control group (traditional teaching method, n = 34) and an experimental group (PTEBL teaching method combined with Caesar, n = 44). Their confidence in their haemostasis skills and willingness to rescue injured victims were investigated before and after the course in both groups. RESULT: Students' self-confidence in their STB skills and the willingness to rescue improved after the class in both groups. Compared with the control group, students in the experimental group were more confident in compressing with bandages and compressing with a tourniquet after a class (compressing with bandages: control group 3.9 ± 0.8 vs. experimental group 4.3 ± 0.7, P = 0.014; compressing with a tourniquet: control group 3.9 ± 0.4 vs. experimental group 4.5 ± 0.8, P = 0.001) More students in the experimental group than the control group thought that the use of Caesar for scenario simulation could improve learning (control group 55.9% vs. experimental group 81.8%, P = 0.024), and using this mannequin led to higher teacher-student interaction (control group 85.3% vs. experimental group 97.7%, P = 0.042). The overall effectiveness of the teaching was better in the experimental group than in the control group (control group 85.3% vs. experimental group 97.7%, P = 0.042). There was a significant positive correlation between teacher-student interactions and the overall effectiveness of teaching (R = 1.000; 95% CI, 1.000-1.000; P < 0.001). CONCLUSION: The PTEBL teaching method combined with Caesar can effectively improve student mastery of STB skills and overcome the shortcomings of traditional teaching methods, which has some promotional value in the training of outstanding doctoral candidates in STB skills.

Do type A personality and neuroticism moderate the relationships of occupational stressors, job satisfaction and burnout among Chinese older nurses? A cross-sectional survey.

BACKGROUND: The high prevalence of burnout among nurses produces huge health service losses. Existing literature found that occupational stressors and low levels of job satisfaction were related to burnout, whilst personality traits such as type A personality and neuroticism influenced occupational stressors, job satisfaction, and burnout. The purpose of this study was to investigate the mediating effect of job satisfaction on the relationship between occupational stressors and burnout among Chinese older nurses, and explore the moderating effects of type A personality and neuroticism on the relationships among occupational stressors, job satisfaction and burnout. METHODS: A cross-sectional study was conducted in five provinces and municipalities (mainly in Shandong) in China. A total of 527 female older nurses (age≧40) were included in this study. Structural equation modelling (SEM) approach was employed to investigate the mediating effect of job satisfaction on the relationship between occupational stressors and burnout. Multi-group analysis was conducted to explore the moderating effects of type A personality and neuroticism on the relationships among occupational stressors, job satisfaction and burnout. RESULTS: Both nurses with high type A personality and high neuroticism had higher occupational stressors, higher burnout and lower job satisfaction. Occupational stressors had direct effect (ß = 0.29, P = 0.001) and indirect effect mediated by low levels of job satisfaction (ß = 0.25, P = 0.001) on burnout. Type A personality had significant moderated effect (P = 0.007) on the relationships among occupational stressors, job satisfaction and burnout, whereas the moderated effect of neuroticism was not significant. CONCLUSIONS: Low levels of job satisfaction mediated the relationship between occupational stressors and burnout among Chinese older nurses, and both the direct and indirect effect of occupational stressors on burnout were moderated by type A personality. Hospital administrators should take specific measures such as transferring older nurses to easier positions to reduce their occupational stress, thereby increasing their job satisfaction and reducing their burnout, which is especially important for the older nurses with high type A personality.

Sinensetin Attenuates Amyloid Beta25-35-Induced Oxidative Stress, Inflammation, and Apoptosis in SH-SY5Y Cells Through the TLR4/NF-κB Signaling Pathway.

Sinensetin (SIN) is an important active compound that exists widely in citrus plants, and has been reported to exhibit various pharmacological properties, including anti-oxidative, anti-inflammatory, and anti-tumor. This study was designed to examine whether SIN can protect against amyloid beta (Aß)-induced neurotoxicity and to elucidate the underlying mechanism. Our results showed that pretreatment with SIN for 1 h, followed by co-treatment with Aß plus SIN for 24 h, attenuated Aß25-35-induced cell viability reduction, oxidative stress, inflammation, and apoptosis in a dose-dependent manner. Aß25-35-induced upregulation of Toll-like receptor 4 (TLR4) expression and nuclear translocation of nuclear factor-kappaB (NF-κB) p65 subunit were inhibited by pretreatment with SIN. Furthermore, the protective effect of SIN was abrogated by TLR4 overexpression. Hence, our data suggested that SIN attenuated Aß25-35-induced neurotoxicity through the TLR4/NF-κB pathway.

High carbohydrate diet induced endoplasmic reticulum stress and oxidative stress, promoted inflammation and apoptosis, impaired intestinal barrier of juvenile largemouth bass (Micropterus salmoides).

This study assessed the effects of feed carbohydrate content on intestinal physical barrier and immunity in juvenile largemouth bass (Micropterus salmoides). Triplicate groups of juvenile fish (4.1 ± 0.2 g) were fed low (LCD, 7%), medium (MCD, 12%) and high (HCD, 17%) carbohydrate diets for eight weeks. Gut histology revealed the slight infiltration of inflammatory cells and moderate loss of mucous membrane layer in HCD group. Expression of ZO1, occluding, and claudin7 genes and epidermal growth factor receptor (EGFR) gene were significantly decreased in HCD group indicating the impairment of tight junction and epithelial cell regeneration. The results showed the significant (P < 0.05) reduction of antioxidant capacity in HCD group compared to LCD. Furthermore, expression of intestinal ERS-related genes such as IRE1, Eif2α, GRP78, CHOPα and CHOPß in HCD group was significantly higher than the LCD group. In addition, HCD induced the up-regulated expression of inflammatory (IL-8, IL-1ß, TNFα and COX2) and apoptosis (TRAF2, bax, casepase3, caspase8 and casepase9) related genes in fish intestine. The data generated in this study clearly demonstrated that HCD induced ERS and oxidative stress, which promoted intestinal inflammation and apoptosis in juvenile largemouth bass.

Interactive effect of thermal and hypoxia on largemouth bass (Micropterus salmoides) gill and liver: Aggravation of oxidative stress, inhibition of immunity and promotion of cell apoptosis.

High temperatures and low oxygen in aquatic environments, such as intensive aquaculture or in natural watersheds, inevitably cause stress in fish. Fish are exposed to high temperatures during the summer, which exacerbates hypoxia. Hypoxia (1.2 ± 0.2 mg/L) under 20 °C (20 HG) and 26 °C (26 HG) was simulated to induce stress in largemouth bass (Micropterus salmoides). Related enzymes and genes involved in antioxidant, immune, and apoptotic responses were selected to explore the interactive effects of temperature and hypoxia on largemouth bass. The results showed that malondialdehyde (MDA) levels in plasma, gill, and liver increased in the 26 HG (p < 0.05). Liver superoxide dismutase (SOD) activity increased in the 26 HG. Peak SOD (SOD1, SOD2, SOD3a, and SOD3b), CAT, and GSH-Px mRNA levels in the gill and liver were observed at 12-24 h of stress. The levels of gill and liver total antioxidant capacity, catalase (CAT), glutathione peroxidase (GSH-Px) activities and other enzyme activities and genes in the 26 HG were higher than those in the 20 HG (p < 0.05). The gill and liver acid phosphatase and alkaline phosphatase activities increased with time in the 26 HG (p < 0.05), while gill and liver lysozyme activities in the 26 HG were lower than those in the 20 HG (p < 0.05). Tumor necrosis factor-α mRNA level was upregulated in the gill and downregulated in the liver at 24 h in the 26 HG. Interleukin (IL)-1ß and IL-8 mRNA levels were upregulated in the gill and liver in the 26 HG at 24 h, whereas IL-15 mRNA level was downregulated in the 26 HG at 12 h. Transforming growth factor-ß1 mRNA level was upregulated in the gill in the 20 HG at 24 h, but downregulated in gill and liver in the 26 HG at 24 h. Similarly, IL-10, Hepcidin-1, and Hepcidin-2 showed lower expression levels in the 26 HG. Gill and liver caspase-3 activities were higher in the 26 HG (p < 0.05), and gill caspase-3 activity was higher than that in the liver. The mRNA levels of proapoptotic genes (caspase-3, caspase-8, and caspase-9) were higher in the 26 HG. The present study demonstrates the interactive effects of temperature and hypoxia on stress in largemouth bass gill and liver. These results will be helpful to understand the mechanisms of stress induced by temperature and hypoxia in fish and provide a theoretical basis for aquaculture management.

Single-Injection Ultrasound-Guided Thoracic Paravertebral Block versus Local Anesthetic Infiltration in Peritoneal Dialysis Catheter Surgeries: A Randomized Controlled Trial.

INTRODUCTION: Ultrasound-guided thoracic paravertebral block (US-TPVB) is generally used for postoperative analgesia. We hypothesized that single-injection US-TPVB could be used as the principal anesthetic technique for a peritoneal dialysis catheter (PDC) procedure (implantation or removal). The anesthetic effect and venous ropivacaine level after a TPVB would be compared with that after local anesthetic infiltration (LAI). METHODS: Patients undergoing PDC procedures were randomized into Group LAI or TPVB. In Group LAI, 40 mL of 0.25% ropivacaine were used. In Group TPVB, single-injection of US-TPVB at T10-T11 level was performed with 20 mL of 0.25% ropivacaine. The quality of anesthesia, visual analogue scale of pain, and venous total plasma ropivacaine level were compared between the 2 groups. RESULTS: Seventy-four eligible patients were enrolled and 38 in Group TPVB. Thirty patients in Group TPVB and 26 patients in Group LAI underwent PDC procedures successfully. Higher satisfaction rates by nephrologists and patients (76.3 and 78.9%) were reported in Group TPVB (44.4 and 44.4% in Group LAI, respectively). The peak venous total plasma ropivacaine concentrations were below the reported toxic threshold in the 2 groups. CONCLUSIONS: A single-injection US-TPVB with 20 mL of 0.25% ropivacaine at T10-T11 could be the principal anesthetic technique for PDC procedures, which provided a comparable anesthetic effect to that of LAI with 40 mL ropivacaine. Higher satisfaction rates by nephrologists and patients were observed in Group TPVB. The 20 mL dose of 0.25% ropivacaine used for an US-TPVB was safe in end-stage renal diseases patients.

Spoof plasmonic waveguide developed from coplanar stripline for strongly confined terahertz propagation and its application in microwave filters.

A novel planar terahertz (THz) plasmonic waveguide developed from coplanar stripline (CPS) is proposed for the first time to achieve strongly confined THz propagation performance based on the concept of spoof surface plasmon polaritons (SSPP). Guided-wave characteristics of the proposed plasmonic waveguide are theoretically investigated by eigen-mode simulation technique and finite-difference time-domain solutions. It is found that the waveguide propagation characteristics can be directly manipulated by designing the SSPP unit cells, which exhibit flexible tuning ability of the asymptotic frequency and strong THz field confinement. The idea has been validated through fabricated filter experiments in microwave frequency regime by scaling up the geometry size of the proposed structure. The measured results illustrate high performance of the ultra-wideband filter, in which the reflection coefficient is better than -10 dB from 3 to 13.1 GHz with the smallest and worst insertion losses of 2.2 dB and 5.6 dB, respectively. This work presents a new SSPP waveguide developed from CPS to realize the THz-wave propagation with strong field confinement, which may have promising potential applications in various integrated THz plasmonic devices.

A Randomized Controlled Trial of Comparing Ultrasound-Guided Transversus Abdominis Plane Block with Local Anesthetic Infiltration in Peritoneal Dialysis Catheter Implantation.

BACKGROUND: The ultrasound-guided transversus abdominis plane (TAP) block has been demonstrated as a useful analgesia technique in lower-abdomen surgeries. We hypothesized that it could be the principal anesthesia technique for end-stage renal disease (ESRD) patients undergoing peritoneal dialysis (PD) catheter (PDC) implantation using the open dissection method. METHODS: This was a single-center, prospective, randomized, and double-blinded study. All eligible patients were randomized into 2 groups: the TAP block group (n = 20) and the local anesthetic infiltration (LAI) group (n = 20). RESULTS: Compared with the LAI group, the TAP block group revealed a remarkably lower visual analogue score, lower switching rate into general anesthesia, higher satisfaction rate, and less rescuing analgesic consumption during operation (p < 0.05). Both PD- and anesthesia-related complications were rare in the 4-week follow-up. CONCLUSIONS: The ultrasound-guided TAP block had better analgesic effect than LAI and can be used as a principal anesthesia technique for PDC implantation in ESRD patients without previous abdominal surgery.

Seasonal Effect on Association between Atmospheric Pollutants and Hospital Emergency Room Visit for Stroke.

BACKGROUND: The relationship between air pollution and stroke is conflicting. This study was conducted to document the relationship between daily changes in atmospheric pollutants and hospital emergency room visits (ERVs) for stroke. METHODS: Data of daily hospital ERVs for stroke and atmospheric pollutants in Changsha city between 2008 and 2009 were collected. Using a time-stratified bidirectional case-crossover design, we analyzed the association between atmospheric pollutants and stroke incidence in 4 seasons. RESULTS: In the single-pollutant model, we found changes in sulfur dioxide (SO2), nitrogen dioxide (NO2), and particulate matters (PM10) were significantly associated with cerebral hemorrhage and cerebral infarction (P < .05) in lags of 0-2 days in autumn. A 10-µg/m3 increase in SO2 in autumn was significantly associated with ERVs for both cerebral hemorrhage (odds ratio [OR], 1.166; 95% confidence interval [CI], 1.012-1.343) and cerebral infarction (OR, 1.214; 95% CI, 1.018-1.448). NO2 in autumn was significantly associated with ERVs for cerebral hemorrhage and infarction with OR = 1.162 (95% CI, 1.005-1.344) and OR = 1.137 (95% CI, 1.011-1.279), respectively. PM10 in autumn was significantly associated with ERVs for cerebral hemorrhage and infarction with OR = 1.147 (95% CI, 1.045-1.259) and OR = 1.091 (95% CI, 1.019-1.168), respectively. Results of the multipollutant model showed that in autumn after PM10 and NO2 adjustment, only a 10-µg/m3 increase in SO2 was significantly associated with ERVs for cerebral infarction (OR, 1.158; 95% CI, 1.006-1.333; P < .05). SO2, NO2, and PM10 were not associated with ERVs for cerebral hemorrhage (P > .05). CONCLUSIONS: This study demonstrates that the change in atmospheric SO2 levels in Changsha is significantly associated with the stroke incidence in autumn.

A Case-Crossover Study between Fine Particulate Matter Elemental Composition and Emergency Admission with Cardiovascular Disease.

BACKGROUND: It is generally understood that Fine Particulate Matter (PM2.5) can cause high blood pressure. However, it remains unclear whether there is a relationship between the elemental composition of PM2.5 and cardiovascular disease in emergency department patients. METHODS: Crossover design for time stratified cases and conditional logistic regression were used to analyze the correlation between emergency admissions for cerebral hemorrhage, cerebral infarction, TIA (Transient ischemic attack), coronary heart disease and PM2.5, concentrations of chemical element compositions, and Particulate Matter 10 (PM10) in Changsha city. RESULTS: When the temperature, atmosphere pressure, maximum wind speed, NO2 and SO2 were adjusted, the OR (Odd Ratio) of cerebral hemorrhage was 1.177 [95% confidence interval (CI): 1.006-1.376, p = 0.04] with every10 µg/m3 increase of PM2.5. PM10 was unrelated to cardiovascular emergencies (p > 0.05). In addition, with each additional IQR (Interquartile Range) increase of Ni, Zn and Pb concentrations in PM2.5, the values of OR were 1.826 (95% CI: 1.031-3.233), 1.568 (95% CI: 1.015-2.423) and 1.682 (95% CI: 1.010-2.800), respectively. CONCLUSIONS: Concentration rises of nickel, zinc and lead elements for PM2.5 in Changsha city were related to the increase of emergency admissions with cerebral hemorrhage.

Regulator of G protein signalling 14 attenuates cardiac remodelling through the MEK-ERK1/2 signalling pathway.

In the past 10 years, several publications have highlighted the role of the regulator of G protein signalling (RGS) family in multiple diseases, including cardiovascular diseases. As one of the multifunctional family members, RGS14 is involved in various biological processes, such as synaptic plasticity, cell division, and phagocytosis. However, the role of RGS14 in cardiovascular diseases remains unclear. In the present study, we used a genetic approach to examine the role of RGS14 in pathological cardiac remodelling in vivo and in vitro. We observed that RGS14 was down-regulated in human failing hearts, murine hypertrophic hearts, and isolated hypertrophic cardiomyocytes. Moreover, the extent of aortic banding-induced cardiac hypertrophy and fibrosis was exacerbated in RGS14 knockout mice, whereas RGS14 transgenic mice exhibited a significantly alleviated response to pressure overload. Furthermore, research of the underlying mechanism revealed that the RGS14-dependent rescue of cardiac remodelling was attributed to the abrogation of mitogen-activated protein kinase (MEK)-extracellular signal-regulated protein kinase (ERK) 1/2 signalling. The results showed that constitutive activation of MEK1 nullified the cardiac protection in RGS14 transgenic mice, and inhibition of MEK-ERK1/2 by U0126 reversed RGS14 deletion-related hypertrophic aggravation. These results demonstrated that RGS14 attenuated the development of cardiac remodelling through MEK-ERK1/2 signalling. RGS14 exhibited great potential as a target for the treatment of pathological cardiac remodelling.

Effective coupled optoelectrical design method for fully infiltrated semiconductor nanowires based hybrid solar cells.

We present a novel coupled design method that both optimizes light absorption and predicts electrical performance of fully infiltrated inorganic semiconductor nanowires (NWs) based hybrid solar cells (HSC). This method provides a thorough insight of hybrid photovoltaic process as a function of geometrical parameters of NWs. An active layer consisting of GaAs NWs as acceptor and poly(3-hexylthiophene-2,5-diyl) (P3HT) as donor were used as a design example. Absorption spectra features were studied by the evolution of the leaky modes and Fabry-Perot resonance with wavelength focusing firstly on the GaAs/air layer before extending to GaAs/P3HT hybrid active layer. The highest absorption efficiency reached 39% for the hybrid active layer of 2 µm thickness under AM 1.5G illumination. Combined with the optical absorption analysis, our method further codesigns the energy harvesting to predict electrical performance of HSC considering exciton dissociation efficiencies within both inorganic NWs and a polymeric shell of 20 nm thickness. The validity of the simulation model was also proved by the well agreement of the simulation results with the published experimental work indicating an effective guidance for future high performance HSC design.

Combined Association of Serum Uric Acid and Metabolic Syndrome with Chronic Kidney Disease in Hypertensive Patients.

BACKGROUND/AIMS: Chronic kidney disease (CKD) is one of the major complications of hypertension. It is not only associated with the future burden of end-stage renal disease but also affects mortality and cardiovascular outcomes caused by hypertension. To help understand the pathogenesis and early prevention of progressive CKD, this large-scale study is designed to determine the complex association between serum uric acid (SUA), metabolic syndrome and the prevalence of CKD in hypertensive patients. METHODS: A total of 19,848 hypertensive subjects were enrolled in this cross-sectional study. Patients with proteinuria and/or an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 were considered CKD cases. RESULTS: Hypertensive subjects with CKD had a higher prevalence of hyperuricemia and metabolic syndrome, as well as higher levels of SUA, BMI, waist circumference (WC), SBP, DBP, TG, fasting blood glucose and lower levels of HDL-C. Compared to patients without CKD, the multivariate-adjusted odds ratios [ORs, 95% confidence interval (CI)] for CKD patients were 2.30 (2.02-2.63) for hyperuricemia, 1.21 (1.04-1.41) for abdominal obesity, 1.21 (1.06-1.38) for elevated TG, 1.29 (1.06-1.56) for low HDL-C, 1.54 (1.36-1.75) for elevated fasting glucose, and 1.49 (1.30-1.71) for metabolic syndrome. Increasing SUA levels and number of individual metabolic syndrome components were associated with an increased prevalence of CKD. Compared with patients classified in the lowest SUA categories and with ≤1 metabolic syndrome components, subjects with HUA and 4 metabolic syndrome components had a 5.77-fold increased OR for CKD based on the multivariate-adjusted analysis. CONCLUSION: Both elevated SUA and metabolic syndrome are associated with an increased prevalence of CKD in hypertensive subjects. Subjects with higher SUA and sum of individual metabolic syndrome components simultaneously have a higher prevalence of CKD.

PICK1 Regulates the Expression and Trafficking of AMPA Receptors in Remifentanil-Induced Hyperalgesia.

BACKGROUND: Remifentanil is used widely in clinical anesthesia because it induces more rapid and more common hyperalgesia than other opioid analgesics. Activation of N-methyl-D-aspartate (NMDA) receptors takes a pivotal part in remifentanil-induced hyperalgesia. Like NMDA receptors, the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are excitatory ion glutamate receptors in postsynaptic membrane, which are involved in the transmission of both acute and chronic pain. Protein interacting with C kinase 1 (PICK1) plays an important role in NMDA receptor-mediated internalization of glutamate receptor 2 (GluR2)-containing AMPARs and contributes to the induction and maintenance of inflammation-induced pain. This study aimed to test the hypothesis that PICK1 contributes to remifentanil-induced hyperalgesia by regulating AMPAR expression and trafficking in the spinal cord. METHODS: Using a rat model of remifentanil-induced hyperalgesia by intravenous infusion of remifentanil, we first measured changes in mechanical and thermal hyperalgesia at 24 hours before remifentanil infusion and 2, 6, 24, and 48 hours after infusion. PICK1 mRNA and protein expression and AMPAR subunit expression and trafficking in the spinal cord were then detected by reverse transcription-qualitative polymerase chain reaction, immunohistochemistry, and Western blot. In addition, we knocked down PICK1 expression by intrathecal administration of PICK1 antisense oligodeoxynucleotide to investigate the effects of PICK1 deficiency on remifentanil-induced hyperalgesia and the expression and trafficking of AMPARs. RESULTS: A significant time-group interaction was found for nociceptive thresholds (paw withdrawal threshold and paw withdrawal latency; all P < .0001). Remifentanil infusion induced distinct hyperalgesia at different time points (P < .0001), which was partly reversed by PICK1 knockdown (P < .007). Besides, remifentanil infusion increased the expression of PICK1 mRNA and protein (P < .0001) and the membrane GluR1 and GluR2 internalization in spinal dorsal horn neurons (P < .0011). More importantly, PICK1 deficiency could attenuate remifentanil-induced GluR2 internalization in the spinal cord dorsal horn (P < .01) but had no effect on remifentanil-induced membrane GluR1 expression (P ≥ .985). CONCLUSIONS: These results indicate that PICK1 deficiency might reverse remifentanil-induced hyperalgesia through regulating GluR2-containing AMPAR expression and trafficking in the spinal cord dorsal horn.

Association between homocysteine and non-alcoholic fatty liver disease in Chinese adults: a cross-sectional study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, and its prevalence is likely to rise even further. To help understand the pathogenesis and early prevention of progressive NAFLD, this large-scale study was designed to explore the potential association between homocysteine and the prevalence of NAFLD. METHODS: A total of 7203 subjects aged 18 years or older were enrolled in this cross-sectional study. The association of homocysteine with the prevalence of NAFLD, in the total sample and stratified by subgroups, was examined using multiple logistic regression analyses. RESULTS: Subjects in the higher quartiles of homocysteine had a higher prevalence of NAFLD. After multivariate adjustment, the odds ratio (OR) for NAFLD in the highest compared with the lowest quartile of homocysteine was 2.08 (95% confidence interval [CI] 1.61, 2.67). Moreover, in the subgroup analyses, we found an effect modification by gender, body mass index (BMI) and smoking status on the association between homocysteine and the prevalence of NAFLD (P for interaction: 0.001, 0.002 and <0.001, respectively). A stronger association was observed in female, obese and non-smoking adults than in male, normal weight and smoking subjects. CONCLUSION: Homocysteine was significantly associated with the prevalence of NAFLD, particularly in female, obese or non-smoking adults.