bluuebunny/crossref_metadata_2025 huggingface dataset:
Control strategies to prevent total hip replacement-related infections: a systematic review and mixed treatment comparison
Authors: Zheng Henry , Barnett Adrian G , Merollini Katharina , Sutton Alex , Cooper Nicola , Berendt Tony , Wilson Jennie , Graves Nicholas
Published: March 2014

Objective

To synthesise the available evidence and estimate the comparative efficacy of control strategies to prevent total hip replacement (THR)-related surgical site infections (SSIs) using a mixed treatment comparison.

Design

Systematic review and mixed treatment comparison.

Setting

Hospital and other healthcare settings.

Participants

Patients undergoing THR.

Primary and secondary outcome measures

The number of THR-related SSIs occurring following the surgical operation.

Results

12 studies involving 123 788 THRs and 9 infection control strategies were identified. The strategy of ‘systemic antibiotics+antibiotic-impregnated cement+conventional ventilation’ significantly reduced the risk of THR-related SSI compared with the referent strategy (no systemic antibiotics+plain cement+conventional ventilation), OR 0.13 (95% credible interval (CrI) 0.03–0.35), and had the highest probability (47–64%) and highest median rank of being the most effective strategy. There was some evidence to suggest that ‘systemic antibiotics+antibiotic-impregnated cement+laminar airflow’ could potentially increase infection risk compared with ‘systemic antibiotics+antibiotic-impregnated cement+conventional ventilation’, 1.96 (95% CrI 0.52–5.37). There was no high-quality evidence that antibiotic-impregnated cement without systemic antibiotic prophylaxis was effective in reducing infection compared with plain cement with systemic antibiotics, 1.28 (95% CrI 0.38–3.38).

Conclusions

We found no convincing evidence in favour of the use of laminar airflow over conventional ventilation for prevention of THR-related SSIs, yet laminar airflow is costly and widely used. Antibiotic-impregnated cement without systemic antibiotics may not be effective in reducing THR-related SSIs. The combination with the highest confidence for reducing SSIs was ‘systemic antibiotics+antibiotic-impregnated cement+conventional ventilation’. Our evidence synthesis underscores the need to review current guidelines based on the available evidence, and to conduct further high-quality double-blind randomised controlled trials to better inform the current clinical guidelines and practice for prevention of THR-related SSIs.
The cross-sectional association of sitting time with carotid artery stiffness in young adults
Authors: Huynh Quan L , Blizzard Christopher L , Sharman James E , Magnussen Costan G , Dwyer Terence , Venn Alison J
Published: March 2014

Objectives

Physical activity is negatively associated with arterial stiffness. However, the relationship between sedentary behaviour and arterial stiffness is poorly understood. In this study, we aimed to investigate the association of sedentary behaviour with arterial stiffness among young adults.

Design

Cross-sectional.

Setting

34 study clinics across Australia during 2004–2006.

Participants

2328 participants (49.4% male) aged 26–36 years who were followed up from a nationally representative sample of Australian schoolchildren in 1985.

Measurements

Arterial stiffness was measured by carotid ultrasound. Sitting time per weekday and weekend day, and physical activity were self-reported by questionnaire. Cardiorespiratory fitness was estimated as physical work capacity at a heart rate of 170 bpm. Anthropometry, blood pressure, resting heart rate and blood biochemistry were measured. Potential confounders, including strength training, education, smoking, diet, alcohol consumption and parity, were self-reported. Rank correlation was used for analysis.

Results

Sitting time per weekend day, but not per weekday, was correlated with arterial stiffness (males r=0.11 p<0.01, females r=0.08, p<0.05) and cardiorespiratory fitness (males r = −0.14, females r = −0.08, p<0.05), and also with fatness and resting heart rate. One additional hour of sitting per weekend day was associated with 5.6% (males p=0.046) and 8.6% (females p=0.05) higher risk of having metabolic syndrome. These associations were independent of physical activity and other potential confounders. The association of sitting time per weekend day with arterial stiffness was not mediated by resting heart rate, fatness or metabolic syndrome.

Conclusions

Our study demonstrates a positive association of sitting time with arterial stiffness. The greater role of sitting time per weekend day in prediction of arterial stiffness and cardiometabolic risk than that of sitting time per weekday may be due to better reflection of discretionary sitting behaviour.
Annual FEV1changes and numbers of circulating endothelial microparticles in patients with COPD: a prospective study
Authors: Takahashi Toru , Kobayashi Seiichi , Fujino Naoya , Suzuki Takaya , Ota Chiharu , Tando Yukiko , Yamada Mitsuhiro , Yanai Masaru , Yamaya Mutsuo , Kurosawa Shin , Yamauchi Masanori , Kubo Hiroshi
Published: March 2014

Objective

Growing evidence suggests that endothelial injury is involved in the pathophysiology of chronic obstructive pulmonary disease (COPD). Circulating endothelial microparticles (EMPs) increase in patients with COPD because of the presence of endothelial injury. We examined the relationship between EMP number and changes in forced expiratory volume in 1 s (FEV1) in patients with COPD.

Design

Prospective study.

Setting

One hospital in Japan.

Participants

A total 48 outpatients with stable COPD coming to the hospital from September 2010 to September 2011.

Primary and secondary outcomes measured

Blood samples were collected and vascular endothelial (VE)-cadherin EMPs (CD144+ EMPs), E-selectin EMPs (CD62E+ EMPs) and platelet endothelial cell adhesion molecule EMPs (CD31+/CD41− EMPs) were measured using fluorescence-activated cell sorting. Annual FEV1changes were evaluated using FEV1data acquired a year before and a year after sample collection.

Results

The number of E-selectin and VE-cadherin EMPs showed significant negative correlations with annual FEV1changes (rs=−0.65, p<0.001, rs=−0.43, p=0.003, respectively). Leucocyte counts tended to be correlated with annual FEV1changes, but this correlation was not significant (rs=−0.28, p=0.057). There were significant differences in annual FEV1changes between with and without history of frequent exacerbation (p=0.006), and among Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages (p=0.009). Multiple linear regression analysis revealed E-selectin EMP to be the only significant parameter associated with annual FEV1changes, independent of VE-cadherin EMP, GOLD stages, leucocyte counts, and history of frequent exacerbation. Receiver operating characteristic curves showed the optimum E-selectin EMP cut-off level for prediction of rapid FEV1decline (>66 mL/year) to be 153.0/µL (areas under curve 0.78 (95% CI 0.60 to 0.89); sensitivity, 67%; specificity, 81%).

Conclusions

The high E-selectin EMP levels in stable patients with COPD are predictive of rapid FEV1decline.

Trial registration number

UMIN000005168.
Pancreatic stone protein (PSP) and pancreatitis-associated protein (PAP): a protocol of a cohort study on the diagnostic efficacy and prognostic value of PSP and PAP as postoperative markers of septic complications in patients undergoing abdominal surgery (PSP study)
Authors: Fisher Oliver Maximilian , Oberkofler Christian Eugen , Raptis Dimitri Aristotle , Soll Christopher , Béchir Markus , Schiesser Marc , Graf Rolf
Published: March 2014

Introduction

Major abdominal surgery leads to a postoperative systemic inflammatory response, making it difficult to discriminate patients with systemic inflammatory response syndrome from those with a beginning postoperative infectious complication. At present, physicians have to rely on their clinical experience to differentiate between the two. Pancreatic stone protein (PSP) and pancreatitis-associated protein (PAP), both secretory proteins produced by the pancreas, are dramatically increased during pancreatic disease and have been shown to act as acute-phase proteins. Increased levels of PSP have been detected in polytrauma patients developing sepsis and PSP has shown a high diagnostic accuracy in discriminating the severity of peritonitis and in predicting death in intensive care unit patients. However, the prognostic value of PSP/PAP for infectious complications among patients undergoing major abdominal surgery is unknown.

Methods and analysis

160 patients undergoing major abdominal surgery will be recruited preoperatively. On the day before surgery, baseline blood values are attained. Following surgery, daily blood samples for measuring regular inflammatory markers (c-reactive protein, procalcitonin, interleukin-6, tumour necrosis factor-α and leucocyte counts) and PSP/PAP will be acquired. PSP/PAP will be measured using a validated ELISA developed in our research laboratory. Patient's discharge marks the end of his/her trial participation. Complication grade including mortality and occurrence of infectious postoperative complications according to validated diagnostic criteria will be correlated with PSP/PAP values. Total intensive care unit days and total length of stay will be recorded as further outcome parameters.

Ethics and dissemination

The PSP trial is a prospective monocentric cohort study evaluating the prognostic value of PSP and PAP for postoperative infectious complications. In addition, a comparison with established inflammatory markers in patients undergoing major abdominal surgery will be performed to help evaluate the role of these proteins in predicting and diagnosing infectious and other postoperative complications.

Institution ethics board approval ID

KEKZH-Nr. STV 11-2009.

Trial registration

ClinicalTrials.gov:NCT01258179.
Protocol for the ProCare Trial: a phase II randomised controlled trial of shared care for follow-up of men with prostate cancer
Authors: Emery Jon , Doorey Juanita , Jefford Michael , King Madeleine , Pirotta Marie , Hayne Dickon , Martin Andrew , Trevena Lyndal , Lim Tee , Constable Roger , Hawks Cynthia , Hyatt Amelia , Hamid Akhlil , Violet John , Gill Suki , Frydenberg Mark , Schofield Penelope
Published: March 2014

Introduction

Men with prostate cancer require long-term follow-up to monitor disease progression and manage common adverse physical and psychosocial consequences of treatment. There is growing recognition of the potential role of primary care in cancer follow-up. This paper describes the protocol for a phase II multisite randomised controlled trial of a novel model of shared care for the follow-up of men after completing treatment for low-moderate risk prostate cancer.

Methods and analysis

The intervention is a shared care model of follow-up visits in the first 12 months after completing treatment for prostate cancer with the following specific components: a survivorship care plan, general practitioner (GP) management guidelines, register and recall systems, screening for distress and unmet needs and patient information resources. Eligible men will have completed surgery and/or radiotherapy for low-moderate risk prostate cancer within the previous 8 weeks and have a GP who consents to participate. Ninety men will be randomised to the intervention or current hospital follow-up care. Study outcome measures will be collected at baseline, 3, 6 and 12 months and include anxiety, depression, unmet needs, prostate cancer-specific quality of life and satisfaction with care. Clinical processes and healthcare resource usage will also be measured. The principal emphasis of the analysis will be on obtaining estimates of the treatment effect size and assessing feasibility in order to inform the design of a subsequent phase III trial.

Ethics and dissemination

Ethics approval has been granted by the University of Western Australia and from all hospital recruitment sites in Western Australia and Victoria.

Results

of this phase II trial will be reported in peer-reviewed publications and in conference presentations.

Trial Registration

Australian New Zealand Clinical Trial Registry ACTRN12610000938000
The impact of transforming healthcare delivery on cystic fibrosis outcomes: a decade of quality improvement at Cincinnati Children’s Hospital
Authors: Siracusa Christopher M , Weiland Jeanne L , Acton James D , Chima Amitra K , Chini Barbara A , Hoberman Andrea J , Wetzel J Denise , Amin Raouf S , McPhail Gary L
Published: March 2014

Background

In 2001, Cincinnati Children's Hospital embarked on a journey to improve healthcare delivery to patients with cystic fibrosis (CF). Data from the Cystic Fibrosis Foundation National Patient Registry revealed our below-average clinical outcomes, prompting us to initiate improvement interventions.

Objective

To improve clinical outcomes for patients with CF through a comprehensive quality-improvement approach directed at increasing patient centredness and improving healthcare delivery.

Interventions

In 2001, we shared our below-average outcomes with patients, families and care providers. We instituted a quality-improvement steering committee with parental and hospital leadership, and our data-management support was restructured to provide real-time clinical data to monitor our progress. In 2002, our weekly chart conference changed to a prospective planning session and individualised daily schedules were created for inpatients. In 2003, an influenza vaccination campaign was initiated and our infection-control practices were redesigned. In 2005, best-practice guidelines were developed for airway-clearance therapy. In 2007, evidence-based clinical algorithms were designed and implemented and key care-team members were added.

Measurements

Primary outcome measures were median forced expiratory volume in 1 s per cent predicted (age range 6–17 years) and median body mass index percentile (age range 2–20 years).

Results

From 2000 to 2010, median forced expiratory volume in 1 s increased from 81.7% to 100.1% predicted and median body mass index increased from the 35th to the 55th centile.

Discussion

By focusing on specific outcomes, empowering families and patients, effectively using data, and standardising care processes, we transformed the culture and delivery of care for our patients with CF and learned valuable lessons potentially translatable to other chronic-care providers.
Accelerating the rate of improvement in cystic fibrosis care: contributions and insights of the learning and leadership collaborative
Authors: Godfrey Marjorie M , Oliver Brant J
Published: March 2014

Introduction

The Learning and Leadership Collaborative (LLC) supports cystic fibrosis (CF) centres’ responses to the variation in CF outcomes in the USA. Between 2002 and 2013, the Cystic Fibrosis Foundation (CFF) designed, tested and modified the LLC to guide front line staff efforts in these efforts. This paper describes the CFF LLC evolution and essential elements that have facilitated increased improvement capability of CF centres and improved CF outcomes.

Methods

CF centre improvement teams across the USA have participated in 11 LLCs of 12 months’ duration since 2002. Based on the Dartmouth Microsystem Improvement Curriculum, the original LLC included face to face meetings, an email listserv, conference calls and completion of between learning session task books. The LLCs evolved over time to include internet based learning, an electronic repository of improvement resources and examples, change ideas driven by evidence based clinical practice guidelines, benchmarking site visits, an applied QI measurement curriculum and team coaching.

Results

Over 90% of the CF centres in the USA have participated in the LLCs and have increased their improvement capabilities. Ten essential elements were identified as contributors to the successful LLCs: LLC national leadership and coordination, local leadership, people with CF and families involvement, registry data transparency, standardised improvement curriculum with evidence based change ideas, internet resources with reminders, team coaching, regular progress reporting and tracking, benchmarking site visits and applied improvement measurement.

Conclusions

The LLCs have contributed to improved medical and process outcomes over the past 10 years. Ten essential elements of the LLCs may benefit improvement efforts in other chronic care populations and health systems.
Doctors’ attitudes towards prescribing opioids for refractory dyspnoea: a single-centred study
Authors: Hadjiphilippou Savvas , Odogwu Sarah-Elizabeth , Dand Pauline
Published: March 2014

Objective

Dyspnoea is a distressing and common symptom in palliative care. There is evidence that opioids can improve the experience of dyspnoea. Limited data suggest that doctors’ attitudes may be a barrier to prescribing opioids for the relief of refractory dyspnoea. This study explored UK hospital doctors’ experience of, and attitudes towards, prescribing opioids for refractory dyspnoea in advanced disease.

Methods

Anonymous semistructured questionnaires were distributed by convenience sampling. Data were collated and descriptive analysis performed. Doctors of all grades attending routine educational events within the medical directorate of a UK district general hospital were included in this study.

Results

Sixty-five questionnaires were analysed. Most doctors (61/64) reported a willingness to prescribe opioids for refractory dyspnoea, although the majority felt less confident than when prescribing opioids for pain. Three-quarters of doctors (49/65) had initiated, or under supervision, prescribed opioids for refractory dyspnoea. This was most often for a patient in the last hours/days of life (44/49), followed by patients with cancer (34/49), heart failure (26/49) and chronic obstructive pulmonary disease (COPD) (21/49). Confidence in prescribing was highest in relation to the dying and lowest in COPD. A significant proportion (40/64) of respondents expressed concerns when prescribing.

Conclusions

This group of doctors was aware of the use of opioids for refractory dyspnoea and reported a willingness to prescribe opioids for this symptom. However, confidence varied considerably depending on clinical context. Fears about side effects were prevalent and should be addressed. Doctors would benefit from clearer guidance on prescribing regimes, specifically in circumstances other than the dying patient.
Influence of nitrogen fertilization on growth and loline alkaloid production of meadow fescue (Festuca pratensis) associated with the fungal symbiont Neotyphodium uncinatum
Authors: Bylin Anja G. , Hume David E. , Card Stuart D. , Mace Wade J. , Lloyd-West Catherine M. , Huss-Danell Kerstin
Published: March 2014

In a field study during two growing seasons in northern Sweden, we assessed meadow fescue (Festuca pratensis Huds.) with and without Neotyphodium uncinatum to determine whether the endophyte affects plant performance regarding tiller and biomass production. In addition, we measured loline alkaloids produced in infected grasses. Approximately 1000 plants grew at two different levels of nitrogen fertilization: the normal amount applied in this region and one-half that amount. Increasing the amount of nitrogen increased the total number of tillers on the plants. Endophyte-infected plants produced more tillers per plant than plants without the endophyte; there was, however, no significant difference in proportion of reproductive tillers, winter survival, or total biomass production between endophyte-infected and noninfected plants. Infected plants produced loline alkaloids in different quantities without indication of being influenced by different nitrogen fertilization levels.
Elastase LasB ofPseudomonas aeruginosapromotes biofilm formation partly through rhamnolipid-mediated regulation
Authors: Yu Hua , He Xiaomei , Xie Wei , Xiong Junzhi , Sheng Halei , Guo Shaodong , Huang Chunji , Zhang Di , Zhang Kebin
Published: March 2014

Elastase LasB, an important extracellular virulence factor, is shown to play an important role in the pathogenicity of Pseudomonas aeruginosa during host infection. However, the role of LasB in the life cycle of P. aeruginosa is not completely understood. This report focuses on the impact of LasB on biofilm formation of P. aeruginosa PAO1. Here, we reported that the lasB deletion mutant (ΔlasB) displayed significantly decreased bacterial attachment, microcolony formation, and extracellular matrix linkage in biofilm associated with decreased biosynthesis of rhamnolipids compared with PAO1 and lasB complementary strain (ΔlasB+). Nevertheless, the ΔlasB developed restored biofilm formation with supplementation of exogenous rhamnolipids. Further gene expression analysis revealed that the mutant of lasB could result in the downregulation of rhamnolipid synthesis at the transcriptional level. Taken together, these results indicated that LasB could promote biofilm formation partly through the rhamnolipid-mediated regulation.
Changes in the Breast Cancer Risk Distribution among Women Utilizing Screening Mammography in Vermont Between 2001 and 2012
Authors: Bolton KC , Mace JL , Vacek PM , Geller BM , Weaver DL , Sprague BL
Published: March 2014

We previously reported a decline in overall breast cancer screening rates in Vermont following 2009. During this period, there has been debate regarding the role of patient context in decisions about when and how often to get screened, as well as increased interest in risk- based screening to optimize the balance between the potential benefits and harms of screening. The purpose of the current study was to evaluate whether the breast cancer risk distribution of the screened population in Vermont has changed during the observed decline in utilization rates. We examined the distribution of breast cancer risk among the screened population in Vermont from 2001 to 2012 using cross-sectional data from the statewide Vermont Breast Cancer Surveillance System. We employed the Breast Cancer Surveillance Consortium risk model to estimate each individual's risk of developing breast cancer within 5 years according to age, breast density, race/ethnicity, family history of breast cancer, and biopsy history. Among women ages 40 to 74 who received screening mammograms, the absolute number of visits dropped by 4,257, from 54,415 to 50,158 (−7.3%; 95% CI: −7.5, −7.1) between 2009 and 2012. Concurrently, the number of screened women who were estimated to be at low risk of developing breast cancer decreased by 4,240 (95% CI: 3,907, 4,573), representing the bulk of the overall decrease. There was no significant change in the aggregate number of women estimated to be at higher risk (−17 women; 95% CI: −350, 316). The outsized proportion of the decline attributed to women at low estimated risk held across younger and older age groups: among women ages 40 to 49, the absolute number screened dropped by 3,337, with 2,495 (95% CI: 2,389, 2,601) reflected by declines among women at low risk; among women ages 50 to 74, the absolute number screened dropped by only 920, however this value reflects a decrease of 1,763 (95% CI: 1,519, 2,007) for the low risk category, and gains totaling 843 (95% CI: 599, 1,087) among higher risk categories. We conclude that the observed decline in women screened in Vermont since 2009 is largely attributable to reductions in visits by women who are estimated to be at low risk of developing breast cancer, and that this trend generally holds across age groups.
Clinical and Genetic Predictors of Impaired Fertility in Female Survivors of Childhood Cancer
Authors: Lupo PJ , Chi CH , Danysh HE , Scheurer ME , Suzawa H , Woodward TL , Kovanci E , Okcu MF , Gibbons WE
Published: March 2014

An important late effect among female survivors of childhood cancer is treatment-related ovarian damage and impaired fertility. While chemotherapy and radiation therapy are associated with impaired fertility, few other risk factors have been identified. Furthermore, little is known about the role of genetic susceptibility to these late effects. Objective: As Anti-Müllerian Hormone (AMH) is a demonstrated marker of ovarian reserve; our objective was to identify clinical and genetic predictors of AMH levels in female survivors of childhood cancer. Methods: Female childhood cancer survivors (n = 181) were recruited from the Texas Children's Cancer Center Long Term Survivor Program (LTSP). AMH (ng/mL) was measured using an enzyme-linked immunosorbent assay. Information on age at diagnosis and enrollment, race, ethnicity, cancer diagnosis, pelvic radiation, and use of alkylating agents was abstracted from medical records. The following single nucleotide polymorphisms (SNPs) were selected based on known or suspected function: AMHR2 rs2002555; CYP2C9*4 rs56165452; CYP2C19*2 rs4244285; and CYP2C19*3 rs4986893. SNPs were genotyped using TaqMan assays. Linear regression was used to determine the association between selected factors and AMH levels. As AMH levels were not normally distributed, the dependent variable was expressed as log10(AMH+1). Results: The mean age at enrollment in the LTSP was 12.4 years. The most common cancer diagnosis was acute lymphoblastic leukemia (47.2%), and a substantial proportion of the population was Hispanic (41.0%). The following variables were significantly associated with lower AMH levels: pelvic radiation (beta = −0.61, P < 0.001) and treatment with alkylating agents (beta = −0.09, P = 0.04). Age at enrollment was associated with higher AMH levels (beta = 0.01, P = 0.04). Hispanic ethnicity was marginally associated with lower AMH levels (beta = −0.08, P = 0.08). There were no significant genetic associations. Conclusions: In one of the largest studies of its kind, our results confirm previous associations between treatment-related factors and ovarian damage. While the SNPs evaluated were not predictive of AMH levels, more work is needed to explain why some survivors experience impaired fertility, while others do not, despite similar therapy.
Retention of Black and White Populations in the Selenium and Vitamin E Cancer Prevention Trial
Authors: Arnold KB , Hermos JA , Anderson KB , Minasian LM , Cook ED
Published: March 2014

Background: Adequate retention of Black (African-American) participants in long-term, randomized trials is important for achieving broadly applicable results. Purpose: To determine the incidence of retention failures and the individual and study site factors associated with retention failure among White and Black participants from the Selenium and Vitamin E Cancer Prevention Trial (SELECT), a phase III study of selenium and vitamin E for prevention of prostate cancer. Methods: SELECT randomized 35,533 participants from 427 study sites. Age eligibility was >55 years for Whites, >50 years for Blacks; race was determined by self-report. The primary analysis included 28,118 (87%) White and 4,322 (13%) Black men. Time to retention failure was defined as days to the earliest of either (1) the second consecutive missed in-person or phone visit or (2) refusal of future contact with study staff. Covariates included participant demographic and clinical characteristics, reasons for participating in SELECT and study site characteristics. Results: In SELECT, Blacks had a higher age-adjusted risk of disengagement than Whites [HR = 1.9; 95% CI 1.7–2.0; p-value < .0001]. Younger Black participants, age 50–54, representing 32% of Black participants, were at three times the risk of disengagement than those age 65+ [HR = 3.34, 95%CI 2.24,4.94, p < .0001]. Blacks age 65+ had 1.6 times the risk of disengagement than Whites age 65+ [HR = 1.58, 95%CI 1.37, 1.83, p < .0001]. By six years post-randomization, 83% of Whites were still retained on the study compared to 68% of Blacks. Among Whites, participant risk factors for disengagement were Hispanic ethnicity, graduate degree, living alone or current smoking; among Blacks, younger age and current smoking were risk factors. The site characteristic associated with disengagement among both racial groups was staff missing SELECT training sessions. Sites with a low staff attendance at training sessions had a high percentage of disengaged participants of either race. Both Whites and Blacks at sites receiving SELECT retention and adherence grants had lower risks for retention failure. Conclusion: These results may be useful in identifying personal and study site characteristics to guide recruitment and enhance retention of both Black and White men in long-term prevention trials.
Interleukin-32 Increases Human Gastric Cancer Cell Invasion Associated with Tumor Progression and Metastasis
Authors: Tsai Chung-Ying , Wang Chia-Siu , Tsai Ming-Ming , Chi Hsiang-Cheng , Cheng Wan-Li , Tseng Yi-Hsin , Chen Cheng-Yi , Lin Crystal D. , Wu Jun-I. , Wang Lu-Hai , Lin Kwang-Huei
Published: March 2014

Purpose: The proinflammatory cytokine interleukin-32 (IL-32) is a novel tumor marker highly expressed in various human carcinomas, including gastric cancer. However, its effects on prognosis of patients with gastric cancer and cancer metastasis are virtually unknown at present. The main aim of this study was to explore the clinical significance of IL-32 in gastric cancer and further elucidate the molecular mechanisms underlying IL-32–mediated migration and invasion.

Experimental Design: Gastric cancer cells with ectopic expression or silencing of IL-32 were examined to identify downstream molecules and establish their effects on cell motility, invasion, and lung metastasis in vivo.

Results: IL-32 was significantly upregulated in gastric cancer and positively correlated with aggressiveness of cancer and poor prognosis. Ectopic expression of IL-32 induced elongated morphology and increased cell migration and invasion via induction of IL-8, VEGF, matrix metalloproteinase 2 (MMP2), and MMP9 expression via phosphor-AKT/phospho-glycogen synthase kinase 3β/active β-catenin as well as hypoxia-inducible factor 1α (HIF-1α) signaling pathways. Conversely, depletion of IL-32 in gastric cancer cells reversed these effects and decreased lung colonization in vivo. Examination of gene expression datasets in oncomine and staining of gastric cancer specimens demonstrated the clinical significance of IL-32 and its downstream molecules by providing information on their coexpression patterns.

Conclusions: IL-32 contributes to gastric cancer progression by increasing the metastatic potential resulting from AKT, β-catenin, and HIF-1α activation. Our results clearly suggest that IL-32 is an important mediator for gastric cancer metastasis and independent prognostic predictor of gastric cancer. Clin Cancer Res; 20(9); 2276–88. ©2014 AACR.
Age-Related Differences in Quality of Standing Balance Using a Composite Score
Authors: Pasma Jantsje H. , Bijlsma Astrid Y. , van der Bij Mark D.W. , Arendzen J. Hans , Meskers Carel G.M. , Maier Andrea B.
Published: March 2014

Background: Age-related differences in standing balance are not detected by testing the ability to maintain balance. Quality of standing balance might be more sensitive to detect age-related differences. Objective: To study age-related differences in quality of standing balance, center of pressure (CoP) movement was evaluated using a wide range of CoP parameters in several standing conditions in healthy young and old participants. Methods: In 35 healthy young (18-30 years) and 75 healthy old (70-80 years) participants, CoP movement was assessed in eight standing conditions on a force plate, including side-by-side, one-leg, semi-tandem and tandem stance, both with eyes open and eyes closed. Direction-specific CoP composite scores were calculated from standardized single CoP parameters (mean amplitude, amplitude variability, mean velocity, velocity variability and range) in anterior-posterior (AP) and medial-lateral (ML) direction. Linear regression analysis was used to detect age-related differences in single CoP parameters and composite scores - adjusted for gender, height and weight. Results: Overall, single CoP parameters were higher in old compared to young participants, but no single CoP parameter consistently demonstrated the largest effect size for all standing conditions. Age-related differences were demonstrated for CoP composite scores in AP direction (tandem eyes open; semi-tandem eyes closed; p < 0.001). CoP composite scores in ML direction were consistently higher for all standing conditions in old compared to young participants (p < 0.001). Conclusion: CoP composite scores in ML direction were the most consistent parameters to detect age-related differences in quality of standing balance in healthy participants and might be of clinical value to detect subtle changes in quality of standing balance.
Contributions of Endoplasmic Reticulum Stress and Reactive Oxygen Species to Renal Injury in Aldosterone/Salt-Induced Rats
Authors: Xu Chengyan , Ding Wei , Yang Lei , Yang Min , Zhang Minmin , Gu Yong
Published: March 2014

Background: Recent studies have suggested that aldosterone (Aldo) plays a key role in the pathogenesis of renal injury; however, the molecular mechanisms of Aldo-induced renal injury have not been characterized. This study was performed to test the hypothesis that reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress contribute to the pathogenesis of Aldo- and salt-induced renal injury. Methods: Rats were uninephrectomized and treated with one of the following for 4 weeks: (1) vehicle, (2) vehicle + NaCl, (3) Aldo + NaCl or (4) Aldo + NaCl + N-acetyl-L-cysteine (NAC). Following this treatment period, the extent of renal injury was assessed by periodic acid-Schiff staining and immunohistochemistry, and the expression levels of proteins related to ER stress, as well as p47phox and p67phox in the kidney, were measured by Western blot. Intracellular ROS generation was evaluated by 2′7′-dichlorofluorescin diacetate fluorescence and ELISA kits. Results: Rats that received Aldo + 1% NaCl exhibited severe renal injury. ROS levels were higher in Aldo-infused rats and were inhibited by NAC. Renal cortical protein levels of GRP78, GRP94, CHOP, ATF-4, p47phox and p67phox were significantly upregulated in rats that received Aldo + 1% NaCl. Treatment with NAC significantly ameliorated the increase in the expression of these proteins. Conclusion: These data suggest that ROS and ER stress play a role in the progression of Aldo- and salt-induced renal injury.
p16/Ki-67 Dual-Stained Cytology Testing May Predict Postpartum Outcome in Patients with Abnormal Papanicolaou Cytology during Pregnancy
Authors: Trutnovsky Gerda , Kolovetsiou-Kreiner Vassiliki , Reich Olaf
Published: March 2014

Objective: To evaluate the use of a new immunocytochemical dual-staining protocol, which allows for the detection of coexpression of the p16INK4a (p16) and Ki-67 biomarkers in prenatal care. It was hypothesized that dual-staining cytology may predict postpartum outcome in patients with abnormal cervical Papanicolaou (Pap) smears during pregnancy. Study Design: In this retrospective pilot study, 27 abnormal Pap smears collected from women during early pregnancy were destained and subsequently stained for p16/Ki-67. Results were correlated with histologic outcome collected during postpartum follow-up. Results: Fourteen of 20 abnormal Pap smears during pregnancy showed a positive p16/Ki-67 dual-stained cytology result, whereas 6 specimens tested negative. Seven cases were excluded due to technical reasons. All 14 patients who were positive for p16/Ki-67 dual stain had cervical intraepithelial neoplasia (CIN) on postpartum histology. In contrast, 5 out of 6 patients negative for p16/Ki-67 dual-staining had a negative histology postpartum and during follow-up, and the remaining patient showed a CIN1 (p < 0.001). Conclusion: p16/Ki-67 dual-stained cytology may provide a valuable novel approach to identify pregnant women with persistent or progressing CIN disease and may help improve the management of abnormal Pap cytology results during pregnancy.
Mesangioproliferative Glomerulonephritis: A 30-Year Prognosis Study
Authors: Axelsen Mette , Smith Pedersen Robert , Heaf James Goya , Ellingsen Torkell
Published: March 2014

Background: Diffuse mesangioproliferative glomerulonephritis (MesP) is the most commonly diagnosed type of glomerulonephritis (GN) in Denmark, with an incidence of 10.8 million per year. In the present study, the 30-year renal survival was estimated. Methods: A retrospective cohort investigation of 140 patients with biopsy-proven MesP was performed between the period 1967-2006. Factors influencing renal survival were investigated using Cox regression analysis. Results: Renal survival at 5, 10, 20 and 30 years was 87, 78, 59 and 50%, respectively. Female survival after 30 years was significantly better than male survival (70 vs. 40%, p = 0.049). Multivariate analysis, adjusted for age, estimated glomerular filtration rate (GFR) and nephrotic syndrome (NS) was performed for each sex individually. An increase in GFR was associated with a hazard risk (HR) of 0.98 (p = 0.02) in women and 0.99 (p = 0.006) in men. Older age was associated with a HR of 1.04 (p = 0.02) in women and 1.03 (p = 0.004) in men. NS had a poorer prognosis in men (HR 2.53, p = 0.01), but not in women (HR 0.54, p = 0.38). Conclusion: Increasing age and decreasing GFR were adversely associated with renal death. Renal prognosis was better for women after 30 years, and NS resulted in a poorer prognosis in men. This suggests that disease course and prognosis are different between men and women.
Scavenger Receptor BI and High-Density Lipoprotein Regulate Thymocyte Apoptosis in Sepsis
Authors: Guo Ling , Zheng Zhong , Ai Junting , Howatt Deborah A. , Mittelstadt Paul R. , Thacker Seth , Daugherty Alan , Ashwell Jonathan D. , Remaley Alan T. , Li Xiang-An
Published: March 2014

Objective—

Thymocyte apoptosis is a major event in sepsis; however, how this process is regulated remains poorly understood.

Approach and Results—

Septic stress induces glucocorticoids production which triggers thymocyte apoptosis. Here, we used scavenger receptor BI (SR-BI)–null mice, which are completely deficient in inducible glucocorticoids in sepsis, to investigate the regulation of thymocyte apoptosis in sepsis. Cecal ligation and puncture induced profound thymocyte apoptosis in SR-BI
+/+
mice, but no thymocyte apoptosis in SR-BI
−/−
mice because of lack of inducible glucocorticoids. Unexpectedly, supplementation of glucocorticoids only partly restored thymocyte apoptosis in SR-BI
−/−
mice. We demonstrated that high-density lipoprotein (HDL) is a critical modulator for thymocyte apoptosis. SR-BI
+/+
HDL significantly enhanced glucocorticoid-induced thymocyte apoptosis, but SR-BI
−/−
HDL had no such activity. Further study revealed that SR-BI
+/+
HDL modulates glucocorticoid-induced thymocyte apoptosis via promoting glucocorticoid receptor translocation, but SR-BI
−/−
HDL loses such regulatory activity. To understand why SR-BI
−/−
HDL loses its regulatory activity, we analyzed HDL cholesterol contents. There was 3-fold enrichment of unesterified cholesterol in SR-BI
−/−
HDL compared with SR-BI
+/+
HDL. Normalization of unesterified cholesterol in SR-BI
−/−
HDL by probucol administration or lecithin cholesteryl acyltransferase expression restored glucocorticoid-induced thymocyte apoptosis, and incorporating unesterified cholesterol into SR-BI
+/+
HDL rendered SR-BI
+/+
HDL dysfunctional. Using lckCre-GR
fl/fl
mice in which thymocytes lack cecal ligation and puncture–induced thymocyte apoptosis, we showed that lckCre-GR
fl/fl
mice were significantly more susceptible to cecal ligation and puncture–induced septic death than GR
fl/fl
control mice, suggesting that glucocorticoid-induced thymocyte apoptosis is required for protection against sepsis.

Conclusions—

The findings in this study reveal a novel regulatory mechanism of thymocyte apoptosis in sepsis by SR-BI and HDL.
Interferon-Induced Transmembrane Protein 1 Regulates Endothelial Lumen Formation During Angiogenesis
Authors: Popson Stephanie A. , Ziegler Mary E. , Chen Xiaofang , Holderfield Matthew T. , Shaaban Cameron I. , Fong Ashley H. , Welch-Reardon Katrina M. , Papkoff Jackie , Hughes Christopher C.W.
Published: March 2014

Objective—

It is well established that angiogenesis is a complex and coordinated multistep process. However, there remains a lack of information about the genes that regulate individual stages of vessel formation. Here, we aimed to define the role of human interferon-induced transmembrane protein 1 (IFITM1) during blood vessel formation.

Approach and Results—

We identified IFITM1 in a microarray screen for genes differentially regulated by endothelial cells (ECs) during an in vitro angiogenesis assay and found that IFITM1 expression was strongly induced as ECs sprouted and formed lumens. We showed by immunohistochemistry that human IFITM1 was expressed by stable blood vessels in multiple organs. siRNA-mediated knockdown of IFITM1 expression spared EC sprouting but completely disrupted lumen formation, in both in vitro and in an in vivo xeno-transplant model. ECs lacking IFITM1 underwent early stages of lumenogenesis (ie, intracellular vacuole formation) but failed to mature or expand lumens. Coimmunoprecipitation studies confirmed occludin as an IFITM1 binding partner in ECs, and immunocytochemistry showed a lack of occludin at endothelial tight junctions in the absence of IFITM1. Finally, time-lapse video microscopy revealed that IFITM1 is required for the formation of stable cell–cell contacts during endothelial lumen formation.

Conclusions—

IFITM1 is essential for the formation of functional blood vessels and stabilizes EC–EC interactions during endothelial lumen formation by regulating tight junction assembly.
Long Noncoding RNA MALAT1 Regulates Endothelial Cell Function and Vessel Growth
Authors: Michalik Katharina M. , You Xintian , Manavski Yosif , Doddaballapur Anuradha , Zörnig Martin , Braun Thomas , John David , Ponomareva Yuliya , Chen Wei , Uchida Shizuka , Boon Reinier A. , Dimmeler Stefanie
Published: March 2014

Rationale:

The human genome harbors a large number of sequences encoding for RNAs that are not translated but control cellular functions by distinct mechanisms. The expression and function of the longer transcripts namely the long noncoding RNAs in the vasculature are largely unknown.

Objective:

Here, we characterized the expression of long noncoding RNAs in human endothelial cells and elucidated the function of the highly expressed metastasis-associated lung adenocarcinoma transcript 1 (MALAT1).

Methods and Results:

Endothelial cells of different origin express relative high levels of the conserved long noncoding RNAs MALAT1, taurine upregulated gene 1 (TUG1), maternally expressed 3 (MEG3), linc00657, and linc00493. MALAT1 was significantly increased by hypoxia and controls a phenotypic switch in endothelial cells. Silencing of MALAT1 by small interfering RNAs or GapmeRs induced a promigratory response and increased basal sprouting and migration, whereas proliferation of endothelial cells was inhibited. When angiogenesis was further stimulated by vascular endothelial growth factor, MALAT1 small interfering RNAs induced discontinuous sprouts indicative of defective proliferation of stalk cells. In vivo studies confirmed that genetic ablation of MALAT1 inhibited proliferation of endothelial cells and reduced neonatal retina vascularization. Pharmacological inhibition of MALAT1 by GapmeRs reduced blood flow recovery and capillary density after hindlimb ischemia. Gene expression profiling followed by confirmatory quantitative reverse transcriptase-polymerase chain reaction demonstrated that silencing of MALAT1 impaired the expression of various cell cycle regulators.

Conclusions:

Silencing of MALAT1 tips the balance from a proliferative to a migratory endothelial cell phenotype in vitro, and its genetic deletion or pharmacological inhibition reduces vascular growth in vivo.
Cortical Hubs and Subcortical Cholinergic Pathways as Neural Substrates of Poststroke Dementia
Authors: Lim Jae-Sung , Kim Nayoung , Jang Min Uk , Han Moon-Ku , Kim SangYun , Baek Min Jae , Jang Myung Suk , Ban Byeolnim , Kang Yeonwook , Kim Dong-Eog , Lee Ji Sung , Lee Juneyoung , Lee Byung-Chul , Yu Kyung-Ho , Black Sandra E. , Bae Hee-Joon
Published: March 2014

Background and Purpose—

A role of neural networks in the development of poststroke dementia has not been clearly established. We hypothesized that stroke-mediated disruption of subcortical cholinergic pathway or large-scale neural networks contributes to poststroke dementia.

Methods—

A matched case–control study was conducted in a predetermined cohort with acute ischemic stroke. Cases were defined as newly developed dementia diagnosed >3 months after stroke using the Korean Vascular Cognitive Impairment Harmonization Standards. Each case was matched to 2 controls for age, education, and initial stroke severity. The Cholinergic Pathways HyperIntensities Scale was applied with some modifications to characterize disruption of cholinergic pathways by acute stroke lesions. Involvement of major cortical hub locations of the default mode network, central executive network, and salience network was also investigated.

Results—

After matching, 38 cases and 66 matched controls were included. Cholinergic Pathways HyperIntensities Scale scores were significantly higher in cases than in controls (2.2±2.9 versus 0.9±1.4). Acute ischemic lesions affecting the default mode and central executive networks were more frequently observed in cases compared with controls (36.8% versus 7.6% and 26.3% versus 6.1%, respectively). These findings remained significant in the multiple logistic regression models adjusted for various sets of potential confounders. Lesion location analysis revealed that cases were more likely to have acute lesions in the left corona radiata, hippocampal formation, and posterior parietal cortex.

Conclusions—

Disruption of cholinergic pathways and major hubs of large-scale neural networks might contribute to newly developed dementia after acute ischemic stroke.
New species of earthworms belonging to the Metaphire formosae species group (Clitellata: Megascolecidae) in Taiwan
Authors: CHANG CHIH-HAN , CHUANG SHU-CHUN , WU JIA HSING , CHEN JIUN-HONG
Published: March 2014

The Metaphire formosae species group is a member of the Pheretima complex of the family Megascolecidae. It is composed of 12 nominal taxa, Metaphire bununa Tsai et al., 2000, Metaphire feijani Chang & Chen, 2004, Metaphire formosae (Michaelsen, 1922), Metaphire glareosa Tsai et al., 2000, Metaphire nanaoensis Chang & Chen, 2005, Metaphire paiwanna paiwanna Tsai et al., 2000, Metaphire paiwanna hengchunensis (James et al., 2005), Metaphire paiwanna liliumfordi Tsai et al., 2000, Metaphire tahanmonta Chang & Chen, 2005, Metaphire taiwanensis Tsai et al., 2004, Metaphire trutina Tsai et al., 2003, and Metaphire yuhsi (Tsai, 1964). In this study, we describe a new species, Metaphire tengjhihensis sp. nov., and two new subspecies, Metaphire nanaoensis truku ssp. nov. and Metaphire taiwanensis tsaii ssp. nov., belonging to this species group. DNA barcodes (partial sequences of the mitochondrial cytochrome c oxidase subunit 1, COI) from type specimens of M. feijani, M. tengjhihensis sp. nov., M. nanaoensis truku ssp. nov., M. tahanmonta and M. taiwanensis tsaii ssp. nov. have been deposited in GenBank in previous studies and are explicitly linked to the type specimens for the first time, enabling unambiguous identification using both morphology and DNA barcodes. Finally, we comment on the systematics of the M. formosae species group and suggest an integrative taxonomic approach that combines morphology and DNA barcodes for future descriptions of new species of Amynthas and Metaphire.