Adult-Onset Transcriptomic Effects of Developmental Exposure to Benzene in Zebrafish (Danio rerio): Evaluating a Volatile Organic Compound of Concern.

Urban environments are afflicted by mixtures of anthropogenic volatile organic compounds (VOCs). VOC sources that drive human exposure include vehicle exhaust, industrial emissions, and oil spillage. The highly volatile VOC benzene has been linked to adverse health outcomes. However, few studies have focused on the later-in-life effects of low-level benzene exposure during the susceptible window of early development. Transcriptomic responses during embryogenesis have potential long-term consequences at levels equal to or lower than 1 ppm, therefore justifying the analysis of adult zebrafish that were exposed during early development. Previously, we identified transcriptomic alteration following controlled VOC exposures to 0.1 or 1 ppm benzene during the first five days of embryogenesis using a zebrafish model. In this study, we evaluated the adult-onset transcriptomic responses to this low-level benzene embryogenesis exposure (n = 20/treatment). We identified key genes, including col1a2 and evi5b, that were differentially expressed in adult zebrafish in both concentrations. Some DEGs overlapped at the larval and adult stages, specifically nfkbiaa, mecr, and reep1. The observed transcriptomic results suggest dose- and sex-dependent changes, with the highest impact of benzene exposure to be on cancer outcomes, endocrine system disorders, reproductive success, neurodevelopment, neurological disease, and associated pathways. Due to molecular pathways being highly conserved between zebrafish and mammals, developmentally exposed adult zebrafish transcriptomics is an important endpoint for providing insight into the long term-effects of VOCs on human health and disease.

Multiscalar Evaluation of the Water Distribution System and Diarrheal Disease Risk in Addis Ababa, Ethiopia.

Despite growing urbanization, our understanding of the impacts of water and sanitation on human health has largely come from studies in rural sectors. To this end, we collected data at both regional (water quality measures from water treatment systems) and community (cross-sectional surveys) scales to examine determinants of enteric pathogen infection and diarrheal disease among infants in Addis Ababa, Ethiopia. Regionally, the Legedadi water treatment plant had significantly lower heterotrophic plate counts, total coliform counts, and fecal coliform counts compared with the Gefersa water treatment plant. The number of pathogen types in infant stool also differed by plant. Decreases in chlorine levels and increases in the relative abundance of Gammaproteobacteria with distance from treatment plants suggest a compromised water distribution system. In communities, infants in households that obtained water from yard pipes or public taps had significantly lower odds of diarrhea compared to households that had water piped into their dwellings (OR = 0.35, 95% CI 0.16, 0.76, and OR = 0.39, 95% CI 0.15, 1.00, respectively). Similarly, infants in households that boiled or filtered water had significantly lower odds of diarrhea compared to households that did not treat water (OR = 0.40, 95% CI 0.19, 0.86 and OR = 0.23, 95% CI 0.06, 0.84, respectively). Integrating multiscalar data better informs the health impacts of water in urban settings.

Association between neutrophil percentage-to-albumin ratio (NPAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and long-term mortality in community-dwelling adults with heart failure: evidence from US NHANES 2005-2016.

BACKGROUND: Heart failure (HF) continues to be the major cause of hospitalizations. Despite numerous significant therapeutic progress, the mortality rate of HF is still high. This longitudianl cohort study aimed to investigate the associations between hematologic inflammatory indices neutrophil percentage-to-albumin ratio (NPAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and all-cause mortality in community-dwelling adults with HF. METHODS: Adults aged 20 and older with HF in the US National Health and Nutrition Examination Survey (NHANES) database 2005-2016 were included and were followed through the end of 2019. Univariate and multivariable Cox regression analyses were performed to determine the associations between the three biomarkers and all-cause mortality. The receiver operating characteristics (ROC) curve analysis was conducted to evaluate their predictive performance on mortality. RESULTS: A total of 1,207 subjects with HF were included, representing a population of 4,606,246 adults in the US. The median follow-up duration was 66.0 months. After adjustment, the highest quartile of NPAR (aHR = 1.81, 95%CI: 1.35, 2.43) and NLR (aHR = 1.59, 95%CI: 1.18, 2.15) were significantly associated with increased mortality risk compared to the lowest quartile during a median follow-up duration of 66.0 months. Elevated PLR was not associated with mortality risk. The area under the ROC curve (AUC) of NPAR, NLR, and PLR in predicting deaths were 0.61 (95%CI: 0.58, 0.65), 0.64 (95%CI: 0.6, 0.67), and 0.58 (95%CI:0.55, 0.61), respectively. CONCLUSIONS: In conclusion, elevated NPAR and NLR but not PLR are independently associated with increased all-cause mortality among community-dwelling individuals with HF. However, the predictive performance of NPAR and NLR alone on mortality was low.

The association between hormone therapy and the risk of lung cancer in postmenopausal women: a 16-year nationwide population-based study.

OBJECTIVE: Although an association between hormone therapy (HT) and the risk of developing lung cancer has been reported, the results on the topic are inconsistent. Our study objective was to investigate whether postmenopausal women who undergo HT exhibit a risk of developing lung cancer. METHODS: In this matched cohort study, we obtained the data of 38,104 postmenopausal women older than 45 years who were treated using HT between 2000 and 2015 from Taiwan's National Health Insurance Research Database, and 152,416 matched participants who were not treated using HT were enrolled as controls at a 1:4 ratio. RESULTS: We used a Cox proportional hazards regression model to identify the risk of developing lung cancer during 16 years of follow-up, and the results indicate no significant difference in the proportion of postmenopausal women treated using HT ( P = 0.129) who developed lung cancer and that of those not treated using HT (0.866% [330 of 38,104] vs 0.950% [1,449 of 152,416]). After adjustment for age and other variables, the adjusted hazard ratio was 0.886 (95% CI, 0.666-1.305, P = 0.433), indicating no association between HT and lung cancer development in postmenopausal women. In a subgroup analysis, the risk of lung cancer was significantly lower in the women who were treated using HT when the HT cumulative dosage was ≥401 mg or when the therapy duration was ≥5 years compared with in those not treated using HT; the adjusted hazard ratios were 0.633 (95% CI, 0.475-0.930; P < 0.001) and 0.532 (95% CI, 0.330-0.934; P < 0.001), respectively, after adjustment. CONCLUSIONS: Our results indicate that HT is not associated with the risk of lung cancer development in postmenopausal women; furthermore, a higher cumulative dosage and the long-term effects of HT reduce the risk of developing lung cancer.

The Performance of Risk Scores for Bleeding and Ischemia as Outcome Predictors in Acute Myocardial Infarction Patients with End-Stage Renal Disease.

Background: In patients with end-stage renal disease (ESRD), acute myocardial infarction (AMI) increases the risks of cardiovascular events, death, and bleeding. Several scores have been developed for predicting ischemic and bleeding outcomes in AMI patients, but none have been validated specifically for ESRD patients. Objectives: To compare and validate different risk scores as predictors of ischemic and bleeding outcomes in AMI patients with ESRD. Methods: This retrospective study enrolled 340 patients who had received percutaneous coronary intervention for AMI while undergoing maintenance hemodialysis for ESRD. Ischemic risk scores (TIMI-STEMI, TIMI-NSTEMI, GRACE, DAPT) and bleeding risk scores (PRECISE-DAPT, CRUSADE, ACUITY, ACTION, SWEDEHEART) were calculated. The ischemic outcome mainly focused on major adverse cardiovascular events (MACEs) within 14 days after hospitalization, and the bleeding outcome was 14-day major bleeding according to the CRUSADE criteria. Results: The GRACE score was superior in discriminating ischemic outcomes, especially in 14-day MACEs [area under curve (AUC) 0.791, p < 0.001]. None of the scores could ideally discriminate 14-day CRUSADE major bleeding, while the PRECISE- DAPT score had the best discriminative power (AUC 0.636, p < 0.001). Either GRACE score > 222 or PRECISE-DAPT score > 48 was associated with higher net adverse cardiovascular events (a composite of 14-day MACEs and 14-day CRUSADE major bleeding). Conclusions: In AMI patients with ESRD, the GRACE score can effectively discriminate the risk of short-term ischemic events. None of the scores could ideally discriminate the bleeding risk, but a high PRECISE-DAPT score still represented a higher rate of bleeding events.

Machine learning ensures rapid and precise selection of gold sea-urchin-like nanoparticles for desired light-to-plasmon resonance.

Sustainable energy strategies, particularly solar-to-hydrogen production, are anticipated to overcome the global reliance on fossil fuels. Thereby, materials enabling the production of green hydrogen from water and sunlight are continuously designed, e.g., ZnO nanostructures coated by gold sea-urchin-like nanoparticles, which employ the light-to-plasmon resonance to realize photoelectrochemical water splitting. But such light-to-plasmon resonance is strongly impacted by the size, the species, and the concentration of the metal nanoparticles coating on the ZnO nanoflower surfaces. Therefore, a precise prediction of the surface plasmon resonance is crucial to achieving an optimized nanoparticle fabrication of the desired light-to-plasmon resonance. To this end, we synthesized a substantial amount of metal (gold) nanoparticles of different sizes and species, which are further coated on ZnO nanoflowers. Subsequently, we utilized a genetic algorithm neural network (GANN) to obtain the synergistically trained model by considering the light-to-plasmon conversion efficiencies and fabrication parameters, such as multiple metal species, precursor concentrations, surfactant concentrations, linker concentrations, and coating times. In addition, we integrated into the model's training the data of nanoparticles due to their inherent complexity, which manifests the light-to-plasmon conversion efficiency far from the coupling state. Therefore, the trained model can guide us to obtain a rapid and automatic selection of fabrication parameters of the nanoparticles with the anticipated light-to-plasmon resonance, which is more efficient than an empirical selection. The capability of the method achieved in this work furthermore demonstrates a successful projection of the light-to-plasmon conversion efficiency and contributes to an efficient selection of the fabrication parameters leading to the anticipated properties.

Evaluating Phenotypic and Transcriptomic Responses Induced by Low-Level VOCs in Zebrafish: Benzene as an Example.

Urban environments are plagued by complex mixtures of anthropogenic volatile organic compounds (VOCs), such as mixtures of benzene, toluene, ethylene, and xylene (BTEX). Sources of BTEX that drive human exposure include vehicle exhaust, industrial emissions, off-gassing of building material, as well as oil spillage and leakage. Among the BTEX mixture, benzene is the most volatile compound and has been linked to numerous adverse health outcomes. However, few studies have focused on the effects of low-level benzene on exposure during early development, which is a susceptible window when hematological, immune, metabolic, and detoxification systems are immature. In this study, we used zebrafish to conduct a VOC exposure model and evaluated phenotypic and transcriptomic responses following 0.1 and 1 ppm benzene exposure during the first five days of embryogenesis (n = 740 per treatment). The benzene body burden was 2 mg/kg in 1 ppm-exposed larval zebrafish pools and under the detection limit in 0.1 ppm-exposed fish. No observable phenotypic changes were found in both larvae except for significant skeletal deformities in 0.1 ppm-exposed fish (p = 0.01) compared with unexposed fish. Based on transcriptomic responses, 1 ppm benzene dysregulated genes that were implicated with the development of hematological system, and the regulation of oxidative stress response, fatty acid metabolism, immune system, and inflammatory response, including apob, nfkbiaa, serpinf1, foxa1, cyp2k6, and cyp2n13 from the cytochrome P450 gene family. Key genes including pik3c2b, pltp, and chia.2 were differentially expressed in both 1 and 0.1 ppm exposures. However, fewer transcriptomic changes were induced by 0.1 ppm compared with 1 ppm. Future studies are needed to determine if these transcriptomic responses during embryogenesis have long-term consequences at levels equal to or lower than 1 ppm.

Multi- and Transgenerational Effects of Developmental Exposure to Environmental Levels of PFAS and PFAS Mixture in Zebrafish (Danio rerio).

Per- and polyfluoroalkyl substances (PFASs) are ubiquitous in the environment and are tied to myriad health effects. Despite the phasing out of the manufacturing of two types of PFASs (perfluorosulfonic acid (PFOS) and perfluorooctanoic acid (PFOA)), chemical composition renders them effectively indestructible by ambient environmental processes, where they thus remain in water. Exposure via water can affect both human and aquatic wildlife. PFASs easily cross the placenta, exposing the fetus at critical windows of development. Little is known about the effects of low-level exposure during this period; even less is known about the potential for multi- and transgenerational effects. We examined the effects of ultra-low, very low, and low-level PFAS exposure (7, 70, and 700 ng/L PFOA; 24, 240, 2400 ng/L PFOS; and stepwise mixtures) from 0-5 days post-fertilization (dpf) on larval zebrafish (Danio rerio) mortality, morphology, behavior and gene expression and fecundity in adult F0 and F1 fish. As expected, environmentally relevant PFAS levels did not affect survival. Morphological abnormalities were not observed until the F1 and F2 generations. Behavior was affected differentially by each chemical and generation. Gene expression was increasingly perturbed in each generation but consistently showed lipid pathway disruption across all generations. Dysregulation of behavior and gene expression is heritable, even in larvae with no direct or indirect exposure. This is the first report of the transgenerational effects of PFOA, PFOS, and their mixture in terms of zebrafish behavior and untargeted gene expression.

Point-of-use carbon-block drinking water filters change gut microbiome of larval zebrafish.

Activated carbon block (ACB) point-of-use (PoU) drinking water filters can change the bacterial composition in drinking water. Consuming ACB PoU filtered water may also influence gut microbiomes. This study uses the zebrafish model to evaluate how the ACB PoU filter affects the gut microbiomes and phenotypic responses in larvae and adulthood. An ACB PoU filter manifold system was constructed to feed larval and adult zebrafish tap and filtered water at the early and late stages of the filter operation period. Adult zebrafish gut microbiomes were not affected by exposure to water types and filter stages. Unlike the adult, gut microbiomes of the larvae exposed to filtered water at the late stage of filter operation were dominated by more filter-relevant bacterial taxa, including Comamonadaceae and Brevundimonas, than the early stage-filtered-water- and tap water-exposed larvae. We also found some fish that were either exposed to filtered water at early and late stages or tap water supplied to the filter toward the end of the experiment showed hyperactive locomotion behaviour, and had significantly lower relative abundances of a Pseudomonas spp. (OTU3) than the normally behaved fish. Our findings indicate that ACB PoU filtered water can alter gut microbiomes and affect the behaviour patterns in larval zebrafish.

Efficacy and Safety of Veno-Arterial Extracorporeal Membrane Oxygenation in the Treatment of High-Risk Pulmonary Embolism: A Retrospective Cohort Study.

Objectives: Veno-arterial extracorporeal membrane oxygenation (ECMO) is increasingly used to treat high-risk pulmonary embolism (PE). However, its efficacy and safety remain uncertain. This retrospective cohort study aimed to determine whether ECMO could improve the clinical outcomes of patients with high-risk PE. Methods: Forty patients with high-risk PE, who were admitted to Kaohsiung Chang Gung Memorial Hospital between January 2012 and December 2019, were included in this study. Demographic data and clinical outcomes were compared between patients treated without ECMO (non-ECMO group) and those treated with ECMO (ECMO group). Appropriate statistical tools were used to compare variables between groups and the survival was analyzed using the Kaplan-Meier method. Results: The overall in-hospital mortality rate was 55%, in which 65% (26/40) of patients presented with cardiac arrest with a mortality rate of 77%, which was higher than that of patients without cardiac arrest (14%). There was no significant difference in major complications and in-hospital mortality between the non-ECMO and ECMO groups. However, in subgroup analysis, compared with patients treated without ECMO, earlier ECMO treatment was associated with a reduced risk of cardiac arrest (P = 0.023) and lower in-hospital mortality (P = 0.036). A log-rank test showed a significantly higher cumulative overall survival in the earlier ECMO treatment group (P = 0.033). Conclusions: In this retrospective cohort study, earlier ECMO treatment was associated with lower in-hospital mortality among unstable patients without cardiac arrest. Our findings suggest that ECMO can be considered as an initial treatment option for patients with high-risk PE in higher-volume hospitals.

Risk Stratification Model for Predicting Coronary Care Unit Readmission.

Background: Use of statistical models for assessing the clinical risk of readmission to medical and surgical intensive care units is well established. However, models for predicting risk of coronary care unit (CCU) readmission are rarely reported. Therefore, this study investigated the characteristics and outcomes of patients readmitted to CCU to identify risk factors for CCU readmission and to establish a scoring system for identifying patients at high risk for CCU readmission. Methods: Medical data were collected for 27,841 patients with a history of readmission to the CCU of a single multi-center healthcare provider in Taiwan during 2001-2019. Characteristics and outcomes were compared between a readmission group and a non-readmission group. Data were segmented at a 9:1 ratio for model building and validation. Results: The number of patients with a CCU readmission history after transfer to a standard care ward was 1,790 (6.4%). The eleven factors that had the strongest associations with CCU readmission were used to develop and validate a CCU readmission risk scoring and prediction model. When the model was used to predict CCU readmission, the receiver-operating curve characteristic was 0.7038 for risk score model group and 0.7181 for the validation group. A CCU readmission risk score was assigned to each patient. The patients were then stratified by risk score into low risk (0-12), moderate risk (13-31) and high risk (32-40) cohorts check scores, which showed that CCU readmission risk significantly differed among the three groups. Conclusions: This study developed a model for estimating CCU readmission risk. By using the proposed model, clinicians can improve CCU patient outcomes and medical care quality.

Developmental Phenotypic and Transcriptomic Effects of Exposure to Nanomolar Levels of 4-Nonylphenol, Triclosan, and Triclocarban in Zebrafish (Danio rerio).

Triclosan, triclocarban and 4-nonylphenol are all chemicals of emerging concern found in a wide variety of consumer products that have exhibited a wide range of endocrine-disrupting effects and are present in increasing amounts in groundwater worldwide. Results of the present study indicate that exposure to these chemicals at critical developmental periods, whether long-term or short-term in duration, leads to significant mortality, morphologic, behavioral and transcriptomic effects in zebrafish (Danio rerio). These effects range from total mortality with either long- or short-term exposure at 100 and 1000 nM of triclosan, to abnormalities in uninflated swim bladder seen with long-term exposure to triclocarban and short-term exposure to 4-nonylphenol, and cardiac edema seen with short-term 4-nonylphenol exposure. Additionally, a significant number of genes involved in neurological and cardiovascular development were differentially expressed after the exposures, as well as lipid metabolism genes and metabolic pathways after exposure to each chemical. Such changes in behavior, gene expression, and pathway abnormalities caused by these three known endocrine disruptors have the potential to impact not only the local ecosystem, but human health as well.

CT characteristics and clinical implications of acute type A aortic intramural hematoma.

Objectives: Computed tomography (CT) has been increasingly used in the diagnosis of acute aortic syndrome, and a number of high-risk CT imaging features have been reported. We aimed to identify CT imaging findings suggesting high-risk for acute aortic syndrome by examining clinical outcomes of patients with acute type A aortic intramural hematoma (TAIMH). Methods: This retrospective study analyzed the relationship of clinical patient characteristics and imaging features with mortality and aortic events in 63 patients receiving initial medical treatment for TAIMH. Multivariate regression analysis was used to determine the predictors of aortic events, and the Kaplan-Meier method was used to analyze survival and aortic events. Results: During a median follow-up of 4.2 years, 25 patients experienced aortic events and 40% of these occurred within 7 days of admission. In total, 12 patients experienced aortic death and 12 patients underwent open aortic surgery or endovascular stenting for aortic disease. In multivariate regression analysis, penetrating atherosclerotic ulcers (PAUs) or ulcer-like projections (ULPs) (P = 0.04) and pericardial effusion (P = 0.03) were independent predictors of aortic events. In the Cox regression model, PAUs/ULPs (P = 0.04) and pericardial effusion (P = 0.04) were independently associated with lower aortic event-free survival. Conclusion: Identification of high-risk CT features is important for clinical decision-making during TAIMH treatment. Early and frequent CT imaging follow-up is required in patients receiving medical treatment. PAUs/ULP and pericardial effusion were the strongest predictors of adverse aortic events.

Weather Impact on Acute Myocardial Infarction Hospital Admissions With a New Model for Prediction: A Nationwide Study.

Introduction: Cardiovascular disease is one of the leading causes of mortality worldwide. Acute myocardial infarction (AMI) is associated with weather change. The study aimed to investigate if weather change was among the risk factors of coronary artery disease to influence AMI occurrence in Taiwan and to generate a model to predict the probabilities of AMI in specific weather and clinical conditions. Method: This observational study utilized the National Health Insurance Research Database and daily weather reports from Taiwan Central Weather Bureau to evaluate the discharge records of patients diagnosed with AMI from various hospitals in Taiwan between January 1, 2008 and December 31, 2011. Generalized additive models (GAMs) were used to estimate the effective parameters on the trend of the AMI incidence rate with respect to the weather and health factors in the time-series data and to build a model for predicting AMI probabilities. Results: A total of 40,328 discharges were listed. The minimum temperature, maximum wind speed, and antiplatelet therapy were negatively related to the daily AMI incidence; however, a drop of 1° when the air temperature was below 15°C was associated with an increase of 1.6% of AMI incidence. By using the meaningful parameters including medical and weather factors, an estimated GAM was built. The model showed an adequate correlation in both internal and external validation. Conclusion: An increase in AMI occurrence in colder weather has been evidenced in the study, but the influence of wind speed remains uncertain. Our analysis demonstrated that the novel GAM model can predict daily onset rates of AMI in specific weather conditions.

Developmental phenotypic and transcriptomic effects of exposure to nanomolar levels of metformin in zebrafish.

Metformin is found in the majority of lakes and streams in the United States, leading to widespread environmental exposure. Results of the present study indicate that extended duration metformin exposure at critical developmental periods leads to decreased survival rates in zebrafish (danio rerio), an NIH approved human model. Significant abnormalities are seen with extended duration metformin exposure from 4 h post fertilization up to 5 days post fertilization, although short term metformin exposure for 24 h at 4-5 days post fertilization did not lead to any significant abnormalities. Both extended and short term duration did however have an impact on locomotor activity of zebrafish, and several genes involved in neurological and cardiovascular development were differentially expressed after exposure to metformin. The changes seen in behavior, gene expression and morphological abnormalities caused by metformin exposure should be examined further in future studies in order to assess their potential human health implications as metformin prescriptions continue to increase worldwide.

Evaluation of Motor Coordination and Antidepressant Activities of Cinnamomum osmophloeum ct. Linalool Leaf Oil in Rodent Model.

Cinnamomum plants (Lauraceae) are a woody species native to South and Southeast Asia forests, and are widely used as food flavors and traditional medicines. This study aims to evaluate the chemical constituents of Cinnamomum osmophloeum ct. linalool leaf oil, and its antidepressant and motor coordination activities and the other behavioral evaluations in a rodent animal model. The major component of leaf oil is linalool, confirmed by GC-MS analysis. Leaf oil would not induce the extra body weight gain compared to the control mice at the examined doses after 6 weeks of oral administration. The present results provide the first evidence for motor coordination and antidepressant effects present in leaf oil. According to hypnotic, locomotor behavioral, and motor coordination evaluations, leaf oil would not cause side effects, including weight gain, drowsiness and a diminishment in the motor functions, at the examined doses. In summary, these results revealed C. osmophloeum ct. linalool leaf essential oil is of high potential as a therapeutic supplement for minor/medium depressive syndromes.

Development and testing of the hemodialysis symptom distress scale (HSD-22) to identify the symptom cluster by using exploratory factor analysis.

BACKGROUND: Patients receiving hemodialysis (HD) often experience multiple symptoms concurrently and these symptoms may impact their quality of life. A valid and reliable tool is needed to assess the symptom distress of patients receiving HD in terms of the perspective of symptom clusters. Although many studies have explored symptom clusters related to patients receiving HD, the clusters formed had problems with overlapping, vagueness, lack of cluster-specificity, and difficulty in discerning their common mechanism under the cluster. AIMS: To develop reliable measurement tool to identify the symptom clusters of patients undergoing HD. DESIGN: A cross-sectional descriptive study. METHODS: To examine the physiological properties of the HD symptom distress (HSD) scale, 216 participants were recruited from a HD center of a medical university hospital in southern Taiwan from February 2019 to April 2019. Construct validity was evaluated by exploratory factor analysis (EFA), and the internal consistency and test-retest reliability were estimated by Cronbach's alpha and intraclass correlation coefficient (ICC). RESULTS: The CVI value of the HSD was 0.89. The HSD scale was composed of five factors with 22 items, including insufficient energy/vitality, cardiac-pulmonary distress, sleep disturbance, musculoskeletal distress, and gastrointestinal distress, with factor loading ranging from 0.62 to 0.87, explaining 65.5% of the total variance. Cronbach's alpha coefficient of the HSD total scale was 0.93, and five subscales ranged from 0.73 to 0.89. The test-retest reliability was 0.92 (p < 0.001) by using the intraclass correlation coefficient (ICC) for the HSD-22 scale. CONCLUSION / IMPLICATION: Theoretical testing from our study indicated that the HSD-22 scale had satisfactory validity and reliability. Therefore, this assessment tool can be employed to identify the symptom clusters of patients receiving HD in the clinical setting. Such identification enables healthcare professionals to provide interventions to release patients' symptom distress efficiently.

Psychometric testing of the hemodialysis self-management instrument (HDSMI-18): A confirmatory factor analysis.

AIM: The aim of this study was to probe the rigorousness of the factor structure of the HDSMI and to test the instrument's construct validity. DESIGN: Cross-sectional study. METHODS: The hemodialysis unit of four hospitals in Taiwan provided data from 628 patients with end-stage renal disease (ESRD), through the period of September to December in 2012. The patients were divided into a calibration sample for CFA and model modification, and a validation sample for cross-validation of the postmodification model. Goodness of fit was tested with standard fit indices. RESULTS: The four latent variables (i.e. partnership, self-care, problem-solving and emotional management) were verified as dimensions of HDSMI through CFA. The construct validity of the HDSMI was improved by omitting two items, allowing one inter-item correlation and transferring the loading of one item. These modifications improved fit indices of the calibration sample. Cross-validation of the validation sample verified the construct validity of the modified HDSMI-18.

Inhibition of ß-Catenin Activity Abolishes LKB1 Loss-Driven Pancreatic Cystadenoma in Mice.

Pancreatic cancer (PC) is the seventh leading cause of cancer death worldwide, and remains one of our most recalcitrant and dismal diseases. In contrast to many other malignancies, there has not been a significant improvement in patient survival over the past decade. Despite advances in our understanding of the genetic alterations associated with this disease, an incomplete understanding of the underlying biology and lack of suitable animal models have hampered efforts to develop more effective therapies. LKB1 is a tumor suppressor that functions as a primary upstream kinase of adenine monophosphate-activated protein kinase (AMPK), which is an important mediator in the regulation of cell growth and epithelial polarity pathways. LKB1 is mutated in a significant number of Peutz-Jeghers syndrome (PJS) patients and in a small proportion of sporadic cancers, including PC; however, little is known about how LKB1 loss contributes to PC development. Here, we report that a reduction in Wnt/ß-catenin activity is associated with LKB1 tumor-suppressive properties in PC. Remarkably, in vivo functional analyses of ß-catenin in the Pdx-1-Cre LKB1L/L ß-cateninL/L mouse model compared to LKB1 loss-driven cystadenoma demonstrate that the loss of ß-catenin impairs cystadenoma development in the pancreas of Pdx-1Cre LKB1L/L mice and dramatically restores the normal development and functions of the pancreas. This study further determined the in vivo and in vitro therapeutic efficacy of the ß-catenin inhibitor FH535 in suppressing LKB1 loss-driven cystadenoma and reducing PC progression that delineates the potential roles of Wnt/ß-catenin signaling in PC harboring LKB1 deficiency.

Impacto da fluticasona intranasal em pacientes com apneia obstrutiva do sono: um estudo prospectivo / The impact of intranasal fluticasone on patients with obstructive sleep apnea: a prospective study

Resumo Introdução: A apneia obstrutiva do sono é o tipo mais comum de apneia do sono, causada por obstrução completa ou parcial da via aérea superior. A obstrução nasal também é considerada como um dos fatores de risco independentes da apneia obstrutiva do sono. Objetivo: Avaliar pacientes com apneia obstrutiva do sono. Método: Pacientes com apneia obstrutiva do sono foram incluídos no estudo de junho a dezembro de 2015, tratados com spray de corticosteroide intranasal por quatro semanas. Vários parâmetros foram obtidos antes e após o tratamento, inclusive os escores da escala Nasal Obstruction Symptom Evaluation, do Pittsburgh Sleep Quality Index e do questionário Escala de Sonolência de Epworth. Resultados: Cinquenta pacientes completaram os questionários antes e após o tratamento intranasal com fluticasona. A média de idade era de 39,7 ± 15,6 anos, com uma proporção de homens para mulheres de 3:2. Os escores pós-tratamento da Escala de Sonolência de Epworth, do Pittsburgh Sleep Quality Index e do Nasal Obstruction Symptom Evaluation indicaram uma diminuição em comparação aos escores pré-tratamento, de 10,4 para 8,74, 7,86 para 6,66 e 9,08 para 6,48, respectivamente. Uma diminuição significativa foi observada no grupo Nasal Obstruction Symptom Evaluation ≥ 10 em todas as três categorias, mas não no grupo Nasal Obstruction Symptom Evaluation <10. Conclusões: Os autores concluíram que o tratamento com fluticasona intranasal pode ser útil em pacientes com apneia obstrutiva do sono relacionada a obstrução nasal para melhorar a qualidade do sono e limitar a disfunção diurna.