Involvement of the extracellular matrix proteins periostin and tenascin C in nasal polyp remodeling by regulating the expression of MMPs

BackgroundTissue remodeling caused by increased MMPs is involved in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). We previously found higher levels of periostin and tenascin C in CRSwNPs, but whether they are associated with the dysregulation of MMPs is unknown. Therefore, the present study aimed to investigate the regulatory roles of these two ECM proteins in the expression of MMPs in nasal polyps.MethodsThe concentrations of MMP‐2, MMP‐3, MMP‐7, MMP‐8, MMP‐9, MMP‐12, MMP‐13, TIMP‐1, TIMP‐2, TIMP‐3, TIMP‐4, periostin, and tenascin C in tissue homogenates of 51 patients with chronic rhinosinusitis with and without nasal polyps and 15 control subjects were measured and were analyzed by adjusted logistic regression and spearman correlation test. Primary human nasal polyp fibroblasts and epithelial cells were stimulated ex vivo with periostin and tenascin C and the gene expression of MMPs and TIMPs was determined by means of real‐time PCR.ResultsThe protein levels of MMP‐3, MMP‐7, MMP‐8, MMP‐9, TIMP‐1, TIMP‐2, periostin, and tenascin C were significantly higher in patients with CRSwNPs than in healthy control subjects. The adjusted logistic regression analyses showed that MMP‐3, MMP‐7, MMP‐8, MMP‐9, TIMP‐2, periostin, and tenascin C were related to the occurrence of CRSwNP. Spearman correlation test showed periostin was positively correlated with MMP‐3 and TIMP‐2, and tenascin C was positively correlated with MMP‐3, MMP‐7, MMP‐8, MMP‐9, and TIMP‐2. Periostin stimulated the gene expression of MMP‐3, MMP‐7, MMP‐8, and MMP‐9 in fibroblasts and MMP‐9 in epithelial cells ex vivo. Tenascin C stimulated the expression of MMP‐3, MMP‐7, MMP‐8, and MMP‐9 in epithelial cells. The expression of TIMPs in fibroblasts and epithelial cells was affected by neither periostin nor tenascin C.ConclusionsPeriostin and tenascin C might be involved in the remodeling of nasal polyps by regulating the expression of different MMPs in epithelial cells and fibroblasts. Our findings have the potential to identify key factors of tissue remodeling in CRSwNPs.     

Development of Oil-in-Gelatin Phantoms for Viscoelasticity Measurement in Ultrasound Shear Wave Elastography

Because tissues consist of solid and fluid materials, their mechanical properties should be characterized in terms of both elasticity and viscosity. Although the elastic properties of tissue-mimicking phantoms have been extensively studied and well characterized in commercially available phantoms, their viscous properties have not been fully investigated. In this article, a set of 14 tissue-mimicking phantoms with different concentrations of gelatin and castor oil were fabricated and characterized in terms of acoustic and viscoelastic properties. The results indicate that adding castor oil to gelatin phantoms decreases shear modulus, but increases shear wave dispersion. For 3% gelatin phantoms containing 0%, 10%, 20% and 40% oil, the measured shear moduli are 2.01 ± 0.26, 1.68 ± 0.25, 1.10 ± 0.22 and 0.88 ± 0.17 kPa, and the Voigt-model coupled shear viscosities are 0.60 ± 0.11, 0.89 ± 0.07, 1.05 ± 0.11 and 1.06 ± 0.13 Pa·s, respectively. The results also confirm that increasing the gelatin concentration increases shear modulus. For phantoms containing 3%, 4%, 5%, 6% and 7% gelatin, the measured shear moduli are 2.01 ± 0.26, 3.10 ± 0.34, 4.18 ± 0.84, 8.05 ± 1.00 and 10.24 ± 1.80 kPa at 0% oil and 1.10 ± 0.22, 1.97 ± 0.20, 3.13 ± 0.63, 4.60 ± 0.60 and 8.43 ± 1.39 kPa at 20% oil, respectively. The phantom recipe developed in this study can be used in validating ultrasound shear wave elastography techniques for soft tissues.     

Dancer perceptions of the cognitive,social, emotional,and physical benefits of modern styles of partnered dancing

ObjectiveTo study dancers’ perceptions of the physical, cognitive, affective, and social benefits of partnered dancing.Method225 dancers (71% female) were recruited through a community ballroom dance center and completed an online survey designed to measure their perceptions of the physical, cognitive, affective, and social benefits of modern, partnered dance styles (swing, Lindy Hop, and ballroom dancing). Subgroups were formed for analyses. For one set of analyses, groups based on length of dance participation were formed: experienced (dancing for more than 2 years) or novice (dancing for less than a year) dancers. For another set of analyses, groups based on frequency of dance practice were formed: committed (dancing at least one or more times per week) or occasional (dancing two or fewer times per month).ResultsThe majority of participants reported perceived benefits in physical fitness, cognition, affect, and social functioning. Experienced dancers reported significantly greater self-perceived physical, social, and cognitive benefits than novice dancers. Committed dancers were more likely than occasional dancers to report improvements in physical fitness, U = 6942, z = 2.38, r = 0.16, p < 0.05. A Mann-Whitney test indicated that self-reported improvements in mood (i.e., feeling less depressed and more happy) were greater for women than for men, U = 3945, z = −3.07, r = 0.20, p < 0.001. Length and frequency of dance participation significantly predicted perceived physical benefits [Χ² (1,6) = 35.463, p <0.001, R² = 0.16] and social benefits [Χ² (1,6) = 15.776, p < 0.05, R² = 0.07], but not cognitive benefits.ConclusionsResults suggest that participation in partnered dance styles is associated with perceived improvements in physical fitness, cognitive functioning, social functioning, mood, and self-confidence, and that perceived benefits may increase as individuals dance more frequently and over longer periods of time.     

Mechanical determinants of early acute ventilatory failure in COPD patients: a physiologic study

Objective  The purpose of this study is to investigate the respiratory mechanics, breathing pattern, and pressure-generating capacity of respiratory muscles during the early phases of an acute exacerbation of COPD. Design  Prospective study. Setting  Division of Emergency Critical Care and Chronic Ventilator Unit. Patients  A total of 24 COPD patients: nine patients requiring ventilatory support because of acute respiratory acidosis due to COPD exacerbation (NPPV group, pH 7.28 ± 0.02); seven patients successfully managed with medical therapy only (SB group, pH 7.39 ± 0.04); eight clinically stable, long term mechanically ventilated, COPD patients (IPPV group). Measurements  Respiratory mechanics during a period of unsupported breathing. Results  A rapid shallow breathing, in the presence of a high drive to breath and a high diaphragmatic tension-time index (TT_di), was found in NPPV and IPPV groups compared to the SB group (f/V _T ratio: 118 ± 43 and 137 ± 65, respectively, versus 37 ± 12 breaths/min/L; P _0.1: 5.0 ± 1.0 and 5.4 ± 1.4, respectively, versus 2.2 ± 0.2 cmH₂O, TT_di: 0.168 ± 0.035 and 0.161 ± 0.039, respectively, versus 0.057 ± 0.033); at variance, PEEPi_dyn was greater in IPPV compared to the other two groups. A significant relationship was observed between TT_di ratio and f/V _T (Rho 0.756). Conclusion  During the early phases of an acute exacerbation, patients with COPD and acute respiratory failure had an imbalance between the decreased capacity of the respiratory muscles to generate pressure and the increased respiratory load. This imbalance was similar to that recorded in patients with COPD and chronic ventilatory failure. In both groups, the imbalance was associated with rapid shallow breathing. Among the mechanical constraints to ventilation, only PEEPi,dyn was different between acute and chronic patients with ventilatory failure. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

输尿管负压吸引鞘在输尿管软镜碎石术中的价值探讨

目的探讨输尿管负压吸引鞘在输尿管软镜碎石术治疗肾结石中的安全性及有效性。方法回顾性分析96例行输尿管软镜碎石术治疗肾结石患者的临床资料,应用输尿管负压吸引鞘46例(治疗组),未应用50例(对照组),比较两组患者的结石清除率、手术时间、肾盂内压、术后肾绞痛、石街形成情况、术后全身炎症反应综合征(SIRS)、降钙素原(PCT)浓度、白细胞计数、住院时间、住院费用和治疗有效率。结果治疗组肾盂内压在最小值、最大值和平均值方面均明显小于对照组(P0.05);在1个月后检查发现,对照组患者治疗有效率为70.0%,清除率为82.0%,而治疗组患者治疗有效率为84.7%,清除率95.6%,治疗组患者结石治疗有效率和清除率明显优于对照组(P0.05);治疗组和对照组手术时间分别为(86.3±5.2)和(108.6±3.5)min,治疗组明显短于对照组(P0.05);对照组和治疗组术后肾绞痛例数分别为13和2例(P0.05);对照组和治疗组术后石街形成例数分别为11和2例(P0.05);对照组和治疗组术后SIRS分别为10和2例,治疗组术后肾绞痛和石街形成、SIRS例数均明显低于对照组(P0.05);对照组和治疗组住院时间分别为(8.8±1.1)和(7.7±1.2)d,住院费用分别为(23 067.5±392.8)和(21 957.3±378.6)元,治疗组住院时间和住院费用与对照组比较差异无统计学意义(P0.05);对照组和治疗组术后PCT分别为(1.5±0.3)和(0.3±0.1)ng/ml,白细胞计数分别为(14.6±0.5)×109/L和(6.4±0.6)×109/L,术后治疗组患者PCT和白细胞计数明显低于对照组(P0.05)。结论输尿管负压吸引鞘在输尿管软镜碎石术治疗肾结石中安全、有效,缩短手术时长,同时提高结石清除率,减少不良反应发生,应当推广。     

The Role of Viscosity Estimation for Oil-in-gelatin Phantom in Shear Wave Based Ultrasound Elastography

Shear wave based ultrasound elastography utilizes mechanical excitation or acoustic radiation force to induce shear waves in deep tissue. The tissue response is monitored to obtain elasticity information about the tissue. During the past two decades, tissue elasticity has been extensively studied and has been used in clinical disease diagnosis. However, biological soft tissues are viscoelastic in nature. Therefore, they should be simultaneously characterized in terms of elasticity and viscosity. In this study, two shear wave-based elasticity imaging methods, shear wave dispersion ultrasound vibrometry (SDUV) and acoustic radiation force impulsive (ARFI) imaging, were compared. The discrepancy between the measurements obtained by the two methods was analyzed, and the role of viscosity was investigated. To this end, four types of gelatin phantoms containing 0%, 20%, 30% and 40% castor oil were fabricated to mimic different viscosities of soft tissue. For the SDUV method, the shear elasticity μ₁ was 3.90 ± 0.27 kPa, 4.49 ± 0.16 kPa, 2.41 ± 0.33 kPa and 1.31 ± 0.09 kPa; and the shear viscosity μ₂ was 1.82 ± 0.31 Pa•s, 2.41 ± 0.35 Pa•s, 2.65 ± 0.13 Pa•s and 2.89 ± 0.14 Pa•s for 0%, 20%, 30% and 40% oil, respectively in both cases. For the ARFI measurements, the shear elasticity μ was 7.30 ± 0.20 kPa, 8.20 ± 0.31 kPa, 7.42 ± 0.21 kPa and 5.90 ± 0.36 kPa for 0%, 20%, 30% and 40% oil, respectively. The SDUV results demonstrated that the elasticity first increased from 0% to 20% oil and then decreased for the 30% and 40% oil. The viscosity decreased consistently as the concentration of castor oil increased from 0% to 40%. The elasticity measured by ARFI showed the same trend as that of the SDUV but exceeded the results measured by SDUV. To clearly validate the impact of viscosity on the elasticity estimation, an independent measurement of the elasticity and viscosity by dynamic mechanical analysis (DMA) was conducted on these four types of gelatin phantoms and then compared with SDUV and ARFI results. The shear elasticities obtained by DMA (3.44 ± 0.31 kPa, 4.29 ± 0.13 kPa, 2.05 ± 0.29 kPa and 1.06 ± 0.18 kPa for 0%, 20%, 30% and 40% oil, respectively) were lower than those by SDUV, whereas the shear viscosities obtained by DMA (2.52 ± 0.32 Pa·s, 3.18 ± 0.12 Pa·s, 3.98 ± 0.19 Pa·s and 4.90 ± 0.20 Pa·s for 0%, 20%, 30% and 40% oil, respectively) were greater than those obtained by SDUV. However, the DMA results showed that the trend in the elasticity and viscosity data was the same as that obtained from the SDUV and ARFI. The SDUV results demonstrated that adding castor oil changed the viscoelastic properties of the phantoms and resulted in increased dispersion of the shear waves. Viscosity can provide important and independent information about the inner state of the phantoms, in addition to the elasticity. Because the ARFI method ignores the dispersion of the shear waves, namely viscosity, it may bias the estimation of the true elasticity. This study sheds further light on the significance of the viscosity measurements in shear wave based elasticity imaging methods.     

Effects of educational intervention on nurses’ knowledge, attitudes, and behavioral intentions toward supplying artificial nutrition and hydration to terminal cancer patients

Introduction  This study aimed to investigate the effects of educational intervention on nurses’ knowledge, attitudes, and behavioral intentions regarding supplying artificial nutrition and hydration (ANH) to terminal cancer patients. Materials and methods  A quasi-experimental design was adopted. A structured questionnaire evaluated the effects of educational intervention. From April to June 2005, 88 nurses were enrolled in the gastroenterology, general surgery, and intensive care unit of Taipei Veterans General Hospital in Taiwan. The nurses were randomly assigned into experimental and control groups in equal numbers (44 nurses in each group). After the experimental and control groups completed the pretest, the experimental group participated in a 50-min lecture. Both groups received a post-test 2 weeks after the lecture. Results  This study showed that prior to educational intervention, nurses have possessed experiences of ANH use in routine caring for terminal cancer patients. However, due to the lack of knowledge about supplying ANH to terminal cancer patients, the nurses trended toward the negative behavioral intention, although they realized the burdens of ANH in these patients. After educational intervention, mean scores of knowledge, attitudes and behavioral intentions of the experimental group increased significantly (z = −5.255, p < 0.001; t = −5.191, p < 0.001; z = −3.274, p ≦ 0.001). Mean score changes of knowledge and attitude between these two groups reached significant differences (t = −7.306, p < 0.001; t = −4.165, p < 0.001), but no significant difference was observed in the mean score change of behavioral intention (z = −1.943, p > 0.05). Conclusion  The educational intervention remarkably improved nurses’ knowledge and attitudes regarding supplying terminal cancer patients with ANH. As for the changes in the behavioral intentions, it requires long-term moral and ethical training and communication. The results of this research emphasized the importance of educational interventions, which should be considered seriously in future reference nursing education program.     

Three LHPP gene‐targeting co‐expressed microRNAs (microRNA‐765, microRNA‐21, and microRNA‐144) promote proliferation,epithelial‐mesenchymal transition,invasion, and are independent prognostic biomarkers in renal cell carcinomas patients

BackgroundRenal cell carcinoma (RCC) is one of the highly malignant tumors in the world. Global Cancer Statistics 2020 estimated that there were 179,368 deaths from kidney tumors. Therefore, exploring the prognostic biomarkers of RCC is of great significance for RCC patients. This study aims to explore the potential mechanism and prognostic value of phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) gene‐targeting co‐expression microRNAs in RCC patients.MethodsA total of 60 RCC patients were included. Quantitative real‐time PCR (qRT‐PCR), western blotting, and immunohistochemistry were used for LHPP, microRNA‐765, microRNA‐21, and microRNA‐144 levels evaluation. Cell Counting Kit‐8 assay, dual‐luciferase reporter gene assay, invasion assay, and RNA fluorescence in situ hybridization were used for functional analyses.ResultsCompared with adjacent tissues, LHPP levels in cancer tissues were significantly increased (p < .001). Herein, we confirmed that microRNA‐765, microRNA‐21, and microRNA‐144 were direct biological targets of LHPP. MicroRNA‐765 (r = −0.570, p < 0.001), microRNA‐21 (r = −0.495, p < .001), and microRNA‐144 (r = −0.463, p < .001) expression levels were negatively correlated with LHPP expression levels. The high expression levels of microRNA‐765, microRNA‐21, and microRNA‐144 in RCC tissues were associated with poor differentiation, recurrence, and poor prognosis (p < .05). In vitro, microRNA‐765, microRNA‐21, and microRNA‐144 act as oncogenes to promote proliferation, invasion, and epithelial‐mesenchymal transition (EMT) through targeting LHPP.ConclusionsMicroRNA‐765, microRNA‐21, and microRNA‐144 are independent risk biomarkers for RCC patients. Inhibiting the expression levels of microRNA‐765, microRNA‐21, and microRNA‐144 can reduce the proliferation, EMT, and invasion of RCC cells. Therefore, the above three microRNAs are expected to become molecular biomarkers for RCC therapy.     

Short-term Evidence in Adults of Anorexigenic Drugs Acting in the Central Nervous System: A Meta-Analysis

PurposeObesity is a chronic clinical condition that is considered one of the most serious health problems in the world because it can cause other chronic metabolic disorders. A meta-analysis was conducted to evaluate the safety and efficacy of 4 central-acting drugs, all approved in Brazil's market for weight loss.MethodsPubMed, EMBASE, and Cochrane library databases were searched from inception until January 2018 to retrieve randomized controlled trials comparing sibutramine, diethylpropion, mazindol, and fenproporex versus placebo in overweight or obese patients. Language was not a restriction for the database searches. We extracted and combined data from studies that reported adverse drug events and weight change. A random effects meta-analytic model was applied in all calculations. The Cochrane Collaboration tool was used to assess the quality and bias of all included studies. Quality of evidence was assessed by using the Grading of Recommendations, Assessment, Development, and Evaluation criteria.FindingsFifty-three studies were included, with a total of 16,903 patients with a median follow-up of 12 weeks (2–260 weeks). The appetite suppressants showed a significant weight loss compared with placebo (mean difference [MD], −4.70 kg; 95% CI, −5.25 to −4.15; I² = 100%; 43 studies). There was an increased total number of adverse events, dry mouth, constipation, insomnia, dizziness, and tachycardia reported in the intervention group (risk ratio [RR], 1.06; 95% CI, 1.01 to 1.10; I² = 20% [22 studies]; RR, 2.08; 95% CI, 1.76 to 2.47; I² = 34% [25 studies]; RR, 2.31; 95% CI, 1.88 to 2.84; I² = 0% [25 studies]; RR, 1.84; 95% CI, 1.40 to 2.39; I² = 0% [17 studies]; RR, 1.78; 95% CI, 1.24 to 2.58; I² = 0% [13 studies]; and RR, 2.01; 95% CI, 1.42 to 2.86; I² = 0% [10 studies], respectively). Sibutramine showed a significant increase in heart rate and mean diastolic pressure compared with placebo (MD, 4.17 beats/min [95% CI, 3.60 to 4.74; I² = 99%; 23 studies]; MD, 1.68 mm Hg [95% CI, 1.29 to 2.07; I² = 98%; 22 studies]).ImplicationsThese drugs are effective for weight loss in overweight and obese patients; however, they increase the risk of adverse events. In fact, the evidence is of low quality, the data availability of studied agents (especially for cardiovascular outcomes) are limited, and the studies are of short duration. PROSPERO identifier: CRD42018091083.     

Short‐term effects of the TNFα antagonist infliximab on the acute phase reaction and activities of daily life in patients with rheumatoid arthritis

Objective. To investigate the short‐term effects of the tumour necrosis factor alpha (TNFα) antagonist infliximab on the acute phase reaction and activities of daily life (ADL) in patients with rheumatoid arthritis (RA). Methods. Fourteen patients with active RA were treated with an intravenous infusion of 200?mg infliximab. The values of the erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP), fibrinogen, granulocyte count, lymphocyte count, platelet count and a patient questionnaire score on ADL, the Health Assessment Questionnaire (HAQ), were obtained at baseline and on days 4 and 14. The significance levels and effect sizes (ESs) of the changes from baseline were calculated. Results. Changes by day 4: The ESs and significance levels were: CRP 1.7, p<0.005; lymphocyte count 1.4, p<0.005; fibrinogen 0.9, p<0.005; ESR 0.7, p<0.005; and HAQ 0.6, p<0.01. Changes by day 14: CRP 1.6, p<0.005; ESR 1.5, p<0.005; fibrinogen 1.3, p<0.005; lymphocyte count 1.0, p<0.005; granulocyte count 0.7, p<0.05; and HAQ 0.6, p<0.05. Conclusion. CRP, fibrinogen and ESR showed the largest ESs and were thus the most sensitive variables showing the early effect of infliximab in this study. The score on ADL (HAQ) showed less ES, but still significant short‐term improvements.     

Refining the therapeutic range of posaconazole and isavuconazole for efficient therapeutic drug monitoring using a bioassay approach

Therapeutic drug monitoring (TDM) of antifungal triazole was recommended, except for isavuconazole (ISA) whose target trough concentrations (C_min) need to be specified. Concerning posaconazole (POS), tablet formulation results in higher exposure but no upper C_min threshold has been yet proposed. We aimed to investigate the pharmacokinetic–pharmacodynamic relationship of POS and ISA, using a bioassay approach as surrogate marker of antifungal activity, in order to refine the therapeutic C_min of both antifungals. A bioassay using a cellulose disk diffusion method was performed to determine the growth inhibition zone (GIZ) of POS and ISA on Aspergillus fumigatus and Candida parapsilosis (ISA only). GIZs of plasma from patients undergoing TDM for POS (n = 136) or ISA (n = 40) were determined. GIZs of plasma patients and antifungal C_min were highly correlated for ISA (A. fumigatus: ρ = 0.942, P < 0.0001; C. parapsilosis: ρ = 0.949, P < 0.0001) and POS (ρ = 0.922, P < 0.0001), and these relationships were represented with a Michaelis–Menten model. Based on this modeling, the recommended thresholds of 0.7, 1, and 1.25 mg/L for the POS C_min corresponded to 50.1, 55.2, and 59.1% of the maximal GIZ, respectively. We propose an upper threshold of 4.8 mg/L for the POS C_min and a lower threshold of 2.0 mg/L for the C_min of ISA, as they respectively corresponded to concentrations leading to 90% and 50% of the maximal GIZ on A. fumigatus. The determination of antifungal activity using this bioassay allowed refining target C_min of POS and ISA, especially the upper threshold of POS (4.8 mg/L) and the lower threshold of ISA (2.0 mg/L).     

PROC,PROCR and PROS1 polymorphisms,plasma anticoagulant phenotypes,and risk of cardiovascular disease and mortality in older adults: the Cardiovascular Health Study

Summary. Background and objectives: Genes encoding protein C anticoagulant pathways are candidates for atherothrombotic and other aging‐related disorders. Methods: Using a tagSNP approach, and data from the Cardiovascular Health Study (CHS), we assessed associations of common polymorphisms of PROC, PROS1 and PROCR with: (i) plasma protein C, soluble protein C endothelial receptor (sEPCR) and protein S levels measured in a subsample of 336 participants at study entry; and (ii) risk of incident clinical outcomes [coronary heart disease (CHD), stroke, and mortality] in 4547 participants during follow‐up. Secondarily, we explored associations between plasma protein C, protein S and sEPCR levels and other candidate genes involved in thrombosis, inflammation, and aging. Results: The PROCR Ser219Gly polymorphism (rs867186) was strongly associated with higher sEPCR levels, explaining 75% of the phenotypic variation. The PROCR Ser219Gly variant was also associated with higher levels of circulating protein C antigen. An IL10 polymorphism was associated with higher free protein S levels. The minor alleles of PROC rs2069901 and PROS1 rs4857343 were weakly associated with lower protein C and free protein S levels, respectively. There was no association between PROCR Ser219Gly and risk of CHD, stroke, or mortality. The minor allele of another common PROCR tagSNP, rs2069948, was associated with lymphoid PROCR mRNA expression and with increased risk of incident stroke and all‐cause mortality, and decreased healthy survival during follow‐up. Conclusions: A common PROCR variant may be associated with decreased healthy survival in older adults. Additional studies are warranted to establish the role of PROCR variants in ischemic and aging‐related disorders.     

Characterization of Thyroid Cancer in Mouse Models Using High-Frequency Quantitative Ultrasound Techniques

Currently, the evaluation of thyroid cancer relies on the use of fine-needle aspiration biopsy, as non-invasive imaging methods do not provide sufficient levels of accuracy for the diagnosis of this disease. In this study, the potential of quantitative ultrasound methods for characterization of thyroid tissues was studied using a rodent model ex vivo. A high-frequency ultrasonic scanning system (40 MHz) was used to scan thyroids extracted from mice that had spontaneously developed thyroid lesions (cancerous or benign). Three sets of mice were acquired having different predispositions to developing three thyroid anomalies: C-cell adenoma, papillary thyroid carcinoma (PTC) and follicular variant papillary thyroid carcinoma (FV-PTC). A fourth set of mice that did not develop thyroid anomalies (normal mice) were used as controls. The backscatter coefficient was estimated from excised thyroid lobes the different mice. From the backscatter coefficient versus frequency (25–45 MHz), the effective scatterer diameter (ESD) and effective acoustic concentration (EAC) were estimated. From the envelope of the backscattered signal, the homodyned K distribution was used to estimate the k parameter (ratio of coherent to incoherent signal energy) and the μ parameter (number of scatterers per resolution cell). Statistically significant differences were observed between cancerous thyroids and normal thyroids based on the ESD, EAC and μ parameters. The mean ESD values were 18.0 ± 0.92, 15.9 ± 0.81 and 21.5 ± 1.80 μm for the PTC, FV-PTC and normal thyroids, respectively. The mean EAC values were 59.4 ± 1.74, 62.7 ± 1.61 and 52.9 ± 3.42 dB (mm⁻³) for the PTC, FV-PTC and normal thyroids, respectively. The mean μ values were 2.55 ± 0.37, 2.59 ± 0.43 and 1.56 ± 0.99 for the PTC, FV-PTC and normal thyroids, respectively. Statistically significant differences were observed between cancerous thyroids and C-cell adenomas based on the ESD and EAC parameters, with an estimated ESD value of 21.3 ± 1.50 μm and EAC value of 54.7 ± 2.24 dB mm⁻³ for C-cell adenomas. These results suggest that high-frequency quantitative ultrasound may enhance the ability to detect and classify diseased thyroid tissues.     

Association between energy cost of walking,muscle activation,and biomechanical parameters in older female fallers and non-fallers

Objective

To determine the nervous activation, muscle strength, and biomechanical parameters that influence the cost of walking in older fallers and non-fallers.

Methods

Maximal voluntary isokinetic torque was measured for the hip, knee and ankle of older women. Oxygen consumption was measured at rest and during 8 min of walking at self-selected speed. An additional minute of walking was performed to collect kinematic variables and the electromyographic signal of trunk, hip, knee, and ankle muscles, which was analyzed by the linear envelope. Cost of walking was calculated by subtracting resting body mass-normalized oxygen consumption from walking body mass-normalized oxygen consumption. Stride time and length, and ankle and hip range of motion were calculated from kinematic data.

Findings

Older adult fallers had 28% lower knee extensor strength (p = 0.02), 47% lower internal oblique activation at heel contact (p = 0.03), and higher coactivation between tibialis anterior and gastrocnemius lateralis in each of the gait phases (p < 0.05). For fallers, a higher activation of gluteus maximus was associated with a higher cost of walking (r = 0.55, p < 0.05 and r = 0.71, p < 0.01, before and after heel contact, respectively). For non-fallers, an association between cost of walking and age (r = 0.60, p = 0.01) and cost of walking and thigh muscle coactivation (r = 0.53, p = 0.01) existed.

Interpretation

This study demonstrated that there may be links between lower-extremity muscle weakness, muscle activation patterns, altered gait, and increased cost of walking in older fallers.     

Unguided Clinical and Actuarial Assessment of Re-offending Risk: A Direct Comparison with Sex Offenders in Denmark

Meta-analyses suggest that actuarial risk assessments outperform unguided clinical judgment for prediction of recidivism in criminal offenders. However, there is a lack of direct comparisons of the predictive accuracy of clinical judgment and actuarial risk scales for sexual offenders. We followed up 121 male sex offenders (≥18 years) subjected to pre-trial forensic psychiatric assessment in Denmark in 1978–1992 (mean post-detainment time = 16.4 years) to compare the predictive validity of unstructured clinical judgment of recidivism risk with that of the well-established Static-99 (Hanson and Thornton, Law and Human Behavior 24:119–136, 2000) and an extension of the Static-99, the Static-2002 (Hanson and Thornton, Notes on the development of Static-2002 (Rep. No. 2003–01), Public Safety and Emergency Preparedness Canada, Ottawa, Canada, 2003). The predictive accuracy of unguided judgment did not exceed chance for any sexual, severe sexual or any violent (sexual or non-sexual) reconviction (AUCs of the ROC curve = 0.52, 95%CI = 0.41–0.63; 0.50, 95%CI = 0.34–0.67; and 0.57, 95%CI = 0.40–0.73, respectively). In contrast, all three outcomes were predicted significantly better than chance by the Static-99 (AUC = 0.62, 95%CI = 0.52–0.72; 0.72, 95%CI = 0.59–0.84; and 0.71, 95%CI = 0.56–0.86) and the Static-2002 (AUC = 0.67, 95%CI = 0.57–0.77; 0.69, 95%CI = 0.56–0.83; and 0.70, 95%CI = 0.55–0.86). Static-99 outperformed clinical judgment for sexual recidivision (χ² = 5.11, df = 1, p < .05). The Static-2002 was significantly more accurate for the prediction of any sexual recidivism as compared to unguided clinical judgment but its advantage fell just short of statistical significance for severe sexual recidivism (χ ² = 3.56, df = 1, p = 0.06). When tested for recidivism within 2 years, none of the three prediction methods yielded results significantly better than chance for any outcome. This direct trial of the unguided clinical method argues against its continued use for risk assessment of sexual offenders.     

应用Logistic回归模型筛选剪切波弹性成像评估颈部淋巴结的定量参数

目的 采用Logistic回归模型探讨剪切波弹性成像(SWE)评估颈部淋巴结良恶性的价值和筛选SWE的定量参数.方法 对59例患者共95个疑似恶性颈部淋巴结在颈部淋巴结清扫前进行常规超声检查及剪切波弹性成像检查,分别比较颈部良性与恶性淋巴结的弹性值比值(E-ratio)、病灶的平均弹性值(E-mean)、病灶的最大弹性值(E-max)和标准差(SD);以病理结果为金标准,建立二分类逻辑回归模型,绘制模型预测概率的ROC曲线并计算曲线下面积,确定诊断界值,计算敏感度、特异度、准确度、阳性预测值、阴性预测值和约登指数.结果 Logistic回归模型为logitic(p)=-3.653+1.760X₁+0.235X₂-0.207X₃+0.168X₄,X₁为E-ratio,X₂为E-mean,X₃为E-max,X₄为SD.模型预测概率ROC曲线的曲线下面积为0.865,以55.66%为模型预测概率的诊断界值时,准确率最高为84.21%,对应的敏感度为80.00%,特异度88.89%,阳性预测值为88.89%,阴性预测值为80.00%,约登指数为68.89%.结论 运用SWE的4个定量参数建立的逻辑回归模型对颈部良恶性淋巴结的鉴别具有中等诊断价值,4个定量参数均可为良恶性淋巴结的鉴别诊断提供依据,而诊断价值最高的定量参数是E-ratio.     

Identification of Putative Cytoskeletal Protein Homologues in the Protozoan Host Hartmannella vermiformis as Substrates for Induced Tyrosine Phosphatase Activity upon Attachment to the Legionnaires' Disease Bacterium,Legionella pneumophila

The Legionnaires'' disease bacterium, Legionella pneumophila, is a facultative intracellular pathogen that invades and replicates within two evolutionarily distant hosts, free living protozoa and mammalian cells. Invasion and intracellular replication within protozoa are thought to be major factors in the transmission of Legionnaires'' disease. We have recently reported the identification of a galactose/N-acetyl-d-galactosamine (Gal/GalNAc) lectin in the protozoan host Hartmannella vermiformis as a receptor for attachment and invasion by L. pneumophila (Venkataraman, C., B.J. Haack, S. Bondada, and Y.A. Kwaik. 1997. J. Exp. Med. 186:537–547). In this report, we extended our studies to the effects of bacterial attachment and invasion on the cytoskeletal proteins of H. vermiformis. We first identified the presence of many protozoan cytoskeletal proteins that were putative homologues to their mammalian counterparts, including actin, pp125^FAK, paxillin, and vinculin, all of which were basally tyrosine phosphorylated in resting H. vermiformis. In addition to L. pneumophila–induced tyrosine dephosphorylation of the lectin, bacterial attachment and invasion was associated with tyrosine dephosphorylation of paxillin, pp125^FAK, and vinculin, whereas actin was minimally affected. Inhibition of bacterial attachment to H. vermiformis by Gal or GalNAc monomers blocked bacteria-induced tyrosine dephosphorylation of detergent-insoluble proteins. In contrast, inhibition of bacterial invasion but not attachment failed to block bacteria-induced tyrosine dephosphorylation of H. vermiformis proteins. This was further supported by the observation that 10 mutants of L. pneumophila that were defective in invasion of H. vermiformis were capable of inducing tyrosine dephosphorylation of H. vermiformis proteins. Entry of L. pneumophila into H. vermiformis was predominantly mediated by noncoated receptor-mediated endocytosis (93%) but coiling phagocytosis was infrequently observed (7%). We conclude that attachment but not invasion by L. pneumophila into H. vermiformis was sufficient and essential to induce protein tyrosine dephosphorylation in H. vermiformis. These manipulations of host cell processes were associated with, or followed by, entry of the bacteria by a noncoated receptor-mediated endocytosis. A model for attachment and entry of L. pneumophila into H. vermiformis is proposed.     

Arterial carbon dioxide tension and outcome in patients admitted to the intensive care unit after cardiac arrest

Background

Arterial carbon dioxide tension (PaCO₂) affects neuronal function and cerebral blood flow. However, its association with outcome in patients admitted to intensive care unit (ICU) after cardiac arrest (CA) has not been evaluated.

Methods and results

Observational cohort study using data from the Australian New Zealand (ANZ) Intensive Care Society Adult-Patient-Database (ANZICS-APD). Outcomes analyses were adjusted for illness severity, co-morbidities, hypothermia, treatment limitations, age, year of admission, glucose, source of admission, PaO₂ and propensity score.We studied 16,542 consecutive patients admitted to 125 ANZ ICUs after CA between 2000 and 2011. Using the APD-PaCO₂ (obtained within 24 h of ICU admission), 3010 (18.2%) were classified into the hypo- (PaCO₂ < 35 mmHg), 6705 (40.5%) into the normo- (35–45 mmHg) and 6827 (41.3%) into the hypercapnia (>45 mmHg) group. The hypocapnia group, compared with the normocapnia group, had a trend toward higher in-hospital mortality (OR 1.12 [95% CI 1.00–1.24, p = 0.04]), lower rate of discharge home (OR 0.81 [0.70–0.94, p < 0.01]) and higher likelihood of fulfilling composite adverse outcome of death and no discharge home (OR 1.23 [1.10–1.37, p < 0.001]). In contrast, the hypercapnia group had similar in-hospital mortality (OR 1.06 [0.97–1.15, p = 0.19]) but higher rate of discharge home among survivors (OR 1.16 [1.03–1.32, p = 0.01]) and similar likelihood of fulfilling the composite outcome (OR 0.97 [0.89–1.06, p = 0.52]). Cox-proportional hazards modelling supported these findings.

Conclusions

Hypo- and hypercapnia are common after ICU admission post-CA. Compared with normocapnia, hypocapnia was independently associated with worse clinical outcomes and hypercapnia a greater likelihood of discharge home among survivors.     

Physiologic response to varying levels of pressure support and neurally adjusted ventilatory assist in patients with acute respiratory failure

Objective  Neurally adjusted ventilatory assist (NAVA) is a new mode wherein the assistance is provided in proportion to diaphragm electrical activity (EAdi). We assessed the physiologic response to varying levels of NAVA and pressure support ventilation (PSV). Setting  ICU of a University Hospital. Patients  Fourteen intubated and mechanically ventilated patients. Design and protocol  Cross-over, prospective, randomized controlled trial. PSV was set to obtain a V t/kg of 6–8 ml/kg with an active inspiration. NAVA was matched with a dedicated software. The assistance was decreased and increased by 50% with both modes. The six assist levels were randomly applied. Measurements  Arterial blood gases (ABGs), tidal volume (V t/kg), peak EAdi, airway pressure (Paw), neural and flow-based timing. Asynchrony was calculated using the asynchrony index (AI). Results  There was no difference in ABGs regardless of mode and assist level. The differences in breathing pattern, ventilator assistance, and respiratory drive and timing between PSV and NAVA were overall small at the two lower assist levels. At the highest assist level, however, we found greater V t/kg (9.1 ± 2.2 vs. 7.1 ± 2 ml/kg, P < 0.001), and lower breathing frequency (12 ± 6 vs. 18 ± 8.2, P < 0.001) and peak EAdi (8.6 ± 10.5 vs. 12.3 ± 9.0, P < 0.002) in PSV than in NAVA; we found mismatch between neural and flow-based timing in PSV, but not in NAVA. AI exceeded 10% in five (36%) and no (0%) patients with PSV and NAVA, respectively (P < 0.05). Conclusions  Compared to PSV, NAVA averted the risk of over-assistance, avoided patient–ventilator asynchrony, and improved patient–ventilator interaction. This article is discussed in the editorial available at: doi:.     

Influence of ADRB1, ADRB2, and COMT Genetic Polymorphisms on Postoperative Outcomes of Patients Undergoing Cardiac Valve Surgery

PurposeThe aim of this study is to prospectively investigate the influence of ADRB and COMT gene polymorphisms on postoperative outcomes of patients undergoing cardiac surgery.MethodsThis prospective cohort study included 223 patients undergoing elective cardiac valve surgery using cardiopulmonary bypass. Demographic information, intraoperative data, postoperative data, and blood samples were collected. Patients were genotyped for single-nucleotide polymorphisms (SNPs) of ADRB1 rs1801253, ADRB2 rs1042713, and COMT rs4680. Major adverse cardiovascular and cerebrovascular events (MACCEs) were used as the primary outcome to evaluate the postoperative prognosis of patients. Secondary outcomes included the duration of mechanical ventilatory support, intensive care unit stay, postoperative hospital stay, and postoperative need of inotropic or vasoactive agents.FindingsThe overall incidence of MACCEs was 15.2%. Among 3 SNP loci, only different genotyped carriers of ADRB2 rs1042713 had statistically significant differences in the incidence of MACCEs (P = 0.005), especially for acute kidney injury (P = 0.023). The proportions of postoperative norepinephrine demand of patients carrying the AA genotype of ADRB2 rs1042713 (P = 0.016) and the AG genotype of COMT rs4680 (P = 0.018) were low. The duration of mechanical ventilatory support (P = 0.034) and postoperative hospital stay (P = 0.045) of patients carrying the AG genotype of COMT rs4680 was shortest. After multiple logistic regression analysis, we found that the G allele carriers of ADRB2 rs1042713 had a higher risk of MACCEs (AG vs AA genotype: odds ratio [OR] = 4.348; 95% CI, 1.529–12.359, P = 0.006; GG vs AA genotype: OR = 3.722; 95% CI, 1.060–13.071; P = 0.040), in particular with acute kidney injury (AG vs AA genotype: OR = 5.273; 95% CI, 1.093–25.451; P = 0.038; GG vs AA genotype: OR = 7.533; 95% CI, 1.275–44.522; P = 0.026). There was no SNP-SNP interaction found among the 3 SNPs with multifactor dimensionality reduction analysis.ImplicationThe ADRB2 rs1042713 polymorphism might be related to prognosis of patients undergoing cardiac surgery. Patients carrying the G allele of ADRB2 rs1042713 had a higher risk of developing MACCEs, especially acute kidney injury. chictr.org.com identifier: ChiCTR1800015105.