Determining weight-bearing tissue condition using peak reactive hyperemia response trend and ultrasonographic features: implications for pressure ulcer prevention

Frequent repositioning is important to prevent pressure ulcer (PU) development, by relieving pressure and recovering damages on skin areas induced by repetitive loading. Although repositioning is the gold standard to prevent PU, there is currently no strategy for determining tissue condition under preventive approaches. In this study, the peak reactive hyperemia (RH) trends and ultrasonographic (US) features are compared with the tissue condition under histopathological examination to determine the potential use of these features in determining the tissue condition noninvasively. Twenty-one male Sprague–Dawley rats (seven per group), with body weight of 385–485 g, were categorized into three groups and subjected to different recovery times, each with three repetitive loading cycles at skin tissues above of right trochanter area. The first, second, and third groups were subjected to short (3 minutes), moderate (10 minutes), and prolonged (40 minutes) recovery, respectively, while applying fixed loading time and pressure (10 minutes and 50 mmHg, respectively), to provide different degree of recovery and tissue conditions (tissue damage and tissue recovery). Peak RH was measured in the three cycles to determine RH trend (increasing, decreasing, and inconsistent). All rat tissues were evaluated using ultrasound at pre- and post-experiment and rated by two raters to categorize the severity of tissue changes (no, mild, moderate, and severe). The tissue condition was also evaluated using histopathological examination to distinguish between normal and abnormal tissues. Most of the samples with increasing RH trend is related to abnormal tissue (71%); while inconsistent RH trends is more related to normal tissue (82%). There is no relationship between the tissue conditions evaluated under ultrasonographic and histopathological examination. Peak RH trend over repetitive loading may serve as a new feature for determining the tissue condition that leading to pressure ulcer

Solid Tumor-Targeted Infiltrating Cytotoxic T Lymphocytes Retained by a Superantigen Fusion Protein

Successful immune-mediated regression of solid tumors is difficult because of the small number of cytotoxic T lymphocytes (CTLs) that were traffic to the tumor site. Here, the targeting of tumor-specific infiltrating CTLs was dependent on a fusion protein consisting of human epidermal growth factor (EGF) and staphylococcal enterotoxin A (SEA) with the D227A mutation. EGF-SEA strongly restrained the growth of murine solid sarcoma 180 (S180) tumors (control versus EGF-SEA, mean tumor weight: 1.013 versus 0.197 g, difference  = 0.816 g). In mice treated with EGF-SEA, CD4+, CD8+ and SEA-reactive T lymphocytes were enriched around the EGFR expressing tumor cells. The EGF receptors were potentially phosphorylated by EGF-SEA stimulation and the fusion protein promoted T cells to release the tumoricidal cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). Intratumoral CTLs secreted cytolytic pore-forming perforins and granzyme B proteins near the surface of carcinomas, causing the death of many tumor cells. We additionally show that labeled EGF-SEA was directly targeted to the tumor tissue after intravenous (i.v.) injection. The findings demonstrate that antibody-like EGF-SEA plays an important role in arresting CTLs in the solid tumor site and has therapeutic potential as a tumor-targeting agent

5′UTR Variants of Ribosomal Protein S19 Transcript Determine Translational Efficiency: Implications for Diamond-Blackfan Anemia and Tissue Variability

Background: Diamond-Blackfan anemia (DBA) is a lineage specific and congenital erythroblastopenia. The disease is associated with mutations in genes encoding ribosomal proteins resulting in perturbed ribosomal subunit biosynthesis. The RPS19 gene is mutated in approximately 25 % of DBA patients and a variety of coding mutations have been described, all presumably leading to haploinsufficiency. A subset of patients carries rare polymorphic sequence variants within the 59untranslated region (59UTR) of RPS19. The functional significance of these variants remains unclear. Methodology/Principal Findings: We analyzed the distribution of transcriptional start sites (TSS) for RPS19 mRNAs in testis and K562 cells. Twenty-nine novel RPS19 transcripts were identified with different 59UTR length. Quantification of expressed w.t. 59UTR variants revealed that a short 59UTR correlates with high levels of RPS19. The total levels of RPS19 transcripts showed a broad variation between tissues. We also expressed three polymorphic RPS19 59UTR variants identified in DBA patients. The sequence variants include two insertions (c.-147_-146insGCCA and c.-147_-146insAGCC) and one deletion (c.-144_-141delTTTC). The three 59UTR polymorphisms are associated with a 20–30 % reduction in RPS19 protein levels when compared to the wild-type (w.t.) 59UTR of corresponding length. Conclusions: The RPS19 gene uses a broad range of TSS and a short 59UTR is associated with increased levels of RPS19. Comparisons between tissues showed a broad variation in the total amount of RPS19 mRNA and in the distribution of TS

Community environmental satisfaction: its forms and impact on migrants' happiness in urban China

BACKGROUND: The great number of internal migrants has become an important part of China's urban population. Improving migrants' well-being is emerging as a key to the state policy emphasized in China's New-type Urbanization Plan. Previous studies on subjective well-being (SWB) have primarily focused on the impacts of objective measures of community environment and consider migrants as a homogeneous group. This study extends the literature by exploring the impacts of perceived community environment on migrants' SWB and incorporating cohort differences in the analysis. METHODS: We use the 2015 national scale data-China Household Financial Survey (CHFS) data-to analyse the different forms of community environmental satisfaction and their impacts on migrants' subjective well-being. A total of 12,607 migrants were sampled from 29 of mainland China's 31 provinces. Latent class analysis is applied to explore the potential forms of community environmental satisfaction; multinomial and ordinal logistic regression models are constructed to examine the sociodemographic characteristics of different forms of community environmental satisfaction and the association between community environmental satisfaction and subjective well-being among migrant cohorts in urban China. RESULTS: Latent class analysis defines four distinctive latent classes, which mirror four different domains of migrants' perception of their local environments. They are called 'unsatisfying local environment', 'satisfying social environment', 'satisfying physical environment', and 'satisfying social life'. Results from the multinomial logistic regression model reveals that the four forms of community environmental satisfaction are underpinned by distinct sociodemographic characteristics. Results from a series of ordinal logistic regression models show that different forms of community environmental satisfaction, in particular satisfaction with the physical environment and with social life, are positively associated with migrants' happiness. The model results also suggest that cohort differences do exist among migrants. The positive effect of a satisfying physical environment on happiness tends to be greater in younger cohorts, while the positive effect of a satisfying social life on SWB is more observable in older cohorts. CONCLUSION: Satisfaction with community environment has a salient impact on urban Chinese migrants' happiness. For their SWB, improving migrants' physical living environments and social lives is relatively more important than social environment, which in a way mirrors migrants' current status with its deficiencies in terms of a comfortable living environment and social life. Moreover, there exist cohort differences that should be considered when making policies to enhance migrants' subjective well-being

A Common Missense Variant in the ATP Receptor P2X7 Is Associated with Reduced Risk of Cardiovascular Events

BACKGROUND AND PURPOSE: Extracellular adenosine triphosphate (ATP) regulates inflammatory cells by activation of the P2X(7) receptor. We hypothesized that polymorphisms in P2RX7 influence the risk of ischemic heart disease (IHD), ischemic stroke (IS) and cardiovascular risk factors and tested this hypothesis using genetic association studies. METHODS: Two loss-of-function SNPs in P2RX7 were genotyped in 1244 IHD cases and 2488 controls as well as 5969 individuals with cardiovascular risk factors. Eleven SNPs in a 250 kb region on chromosome 12 spanning P2RX7 as well as neighboring genes OASL, P2RX4 and CAMKK2 were genotyped in 4138 individuals with IS and 2528 controls. Association was examined using linear and logistic regression models with an additive genetic model. RESULTS: The common loss-of-function variant rs3751143 was significantly associated with a decreased risk of IHD in smokers (P = 0.03) as well as decreased risk of IS (OR 0.89; 95% CI = 0.81-0.97; P = 0.012). In addition, an intronic SNP in CAMKK2, rs2686342, were associated with a decreased risk of IS (OR 0.89; 95% CI = 0.82-0.97; P = 0.011). In subgroup analyses, both SNPs were associated with decreased risk of IS in individuals with hypertension (P = 0.045 and 0.015, respectively). CONCLUSIONS: A common loss-of-function missense variant in the gene encoding the P2X(7) receptor is associated with reduced risk of IS and with IHD in smokers. These findings might implicate a role of purinergic signaling in atherogenesis or atherothrombosis

Discovery of Genetic Variation on Chromosome 5q22 Associated with Mortality in Heart Failure

Failure of the human heart to maintain sufficient output of blood for the demands of the body, heart failure, is a common condition with high mortality even with modern therapeutic alternatives. To identify molecular determinant

Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection

The potential for ischemic preconditioning to reduce infarct size was first recognized more than 30 years ago. Despite extension of the concept to ischemic postconditioning and remote ischemic conditioning and literally thousands of experimental studies in various species and models which identified a multitude of signaling steps, so far there is only a single and very recent study, which has unequivocally translated cardioprotection to improved clinical outcome as the primary endpoint in patients. Many potential reasons for this disappointing lack of clinical translation of cardioprotection have been proposed, including lack of rigor and reproducibility in preclinical studies, and poor design and conduct of clinical trials. There is, however, universal agreement that robust preclinical data are a mandatory prerequisite to initiate a meaningful clinical trial. In this context, it is disconcerting that the CAESAR consortium (Consortium for preclinicAl assESsment of cARdioprotective therapies) in a highly standardized multi-center approach of preclinical studies identified only ischemic preconditioning, but not nitrite or sildenafil, when given as adjunct to reperfusion, to reduce infarct size. However, ischemic preconditioning—due to its very nature—can only be used in elective interventions, and not in acute myocardial infarction. Therefore, better strategies to identify robust and reproducible strategies of cardioprotection, which can subsequently be tested in clinical trials must be developed. We refer to the recent guidelines for experimental models of myocardial ischemia and infarction, and aim to provide now practical guidelines to ensure rigor and reproducibility in preclinical and clinical studies on cardioprotection. In line with the above guideline, we define rigor as standardized state-of-the-art design, conduct and reporting of a study, which is then a prerequisite for reproducibility, i.e. replication of results by another laboratory when performing exactly the same experiment

Difference between using 2 and 4 meter receiver height in railway noise prediction

In the Nordic countries a receiver height of 2 m has often been used when calculating noise levels over large areas for socioacoustic surveys, but within the EU 4 m is used. Here results are presented for railway noise calculations at both heights in 1459 points across several areas in Sweden. The average difference in equivalent level is 2.5 dB higher at 4 m height than at 2 m, which in turn leads to 10 % \u96 40 % less predicted annoyance if the exposure is calculated at 4 m