bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations of psychological distress with positive psychological variables and activities of daily living among stroke patients: a cross-sectional study
Authors: Wang Xiaoxi , Shang Shengjie , Yang Huazhe , Ai Hua , Wang Yin , Chang Shijie , Sha Xianzheng , Wang Lie , Jiang Xiran
Published: December 2019

Background

Depression and anxiety result in psychological distress, which can further affect mental status and quality of life in stroke patients. Exploring the associations between positive psychological variables and symptoms of psychological distress following stroke is of great significance for further psychological interventions.

Methods

A total of 710 stroke patients from the five largest cities in Liaoning Province in China were enrolled into the present study in July 2014. All patients independently completed the questionnaires with respect to psychological distress and positive psychological variables. Depressive and anxiety symptoms were evaluated using Center for Epidemiologic Studies Depression Scale (CES-D) and Self-Rating Anxiety Scale, respectively. Positive psychological variables were evaluated using Perceived Social Support Scale, Adult Hope Scale (AHS), General Perceived Self-Efficacy Scale and Resilience Scale-14 (RS-14). Activities of Daily Living (ADL) was measured using Barthel Index. Factors associated with psychological variables and depressive and anxiety symptoms were identified using t-test, ANOVA, correlation and hierarchical linear regression analysis.

Results

Depressive and anxiety symptoms were present in 600 of 710 (84.51%) and 537 of 710 (75.63%) stroke patients enrolled, respectively.

Social support (β = − 0.111, p < 0.001) and hope (β = − 0.120, p < 0.001) were negatively associated with both depressive and anxiety symptoms.

Resilience (β = − 0.179, p < 0.001) was negatively associated with depressive symptoms.

Self-efficacy (β = − 0.135, p < 0.001) was negatively associated with anxiety symptoms. Hierarchical regression analyses indicated that ADL accounted for 10.0 and 6.0% of the variance of depressive and anxiety symptoms, respectively.

Social support, resilience, self-efficacy and hope as a whole accounted for 7.5 and 5.3% of the variance of depressive and anxiety symptoms.

Conclusions

The high frequency of depressive and anxiety symptoms among Chinese stroke survivors should receive attentions from all stakeholders. Findings suggested that intervention strategies on ADL, social support, hope, resilience and self-efficacy could be developed to improve psychosocial outcomes for stroke survivors.
Surgical treatment to multiple primary lung cancer patients: a systematic review and meta-analysis
Authors: Chen Ting-Fei , Xie Chun-Ying , Rao Bing-Yu , Shan Shi-Chao , Zhang Xin , Zeng Bo , Lei Yi-Yan , Luo Hong-He
Published: December 2019

Background

As there is no consensus on the optimal surgery strategy for multiple primary lung cancer (MPLC), we conducted this study to address this issue by comparing the prognosis of MPLC patients underwent different surgical strategies including sublobar resection and the standard resection through a systemic review and meta-analysis.

Methods

Relevant literature was obtained from three databases including PubMed, Embase and Web of Science. Inclusion and exclusion criteria were set for the screening of articles to be selected for further conduction of systemic review and meta-analysis. The HRs of OS of the sublobar group compared with standard resection group were extracted directly or calculated indirectly from included researches.

Results

Ten researches published from 2000 to 2017 were included in this study, with 468 and 445 MPLC cases for the standard resection group and sublobar resection group respectively. The result suggested that OS of MPLC patients underwent sublobar resection (segmentectomy or wedge resection for at least one lesion) was comparable with those underwent standard resection approach (lobectomy or pneumonectomy for all lesions), with HR 1.07, 95% CI 0.67–1.71, p = 0.784. Further analysis found no difference in subgroups of synchronous and metachronous (from second metachronous lesion), different population region and dominant sex type.

Conclusions

This study may reveal that sublobar resection is acceptable for patients with MPLC at an early stage, because of the equivalent prognosis to the standard resection and better pulmonary function preservation. Further research is needed to validate these findings.
Cost-effectiveness of insulin degludec versus insulin glargine U100 in adults with type 1 and type 2 diabetes mellitus in Bulgaria
Authors: Russel-Szymczyk Monika , Valov Vasil , Savova Alexandra , Manova Manoela
Published: December 2019

Background

This analysis evaluates the cost-effectiveness of insulin degludec (degludec) versus biosimilar insulin glargine U100 (glargine U100) in patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM) in Bulgaria.

Methods

A simple, short-term model was used to compare the treatment costs and outcomes associated with hypoglycaemic events with degludec versus glargine U100 in patients with T1DM and T2DM from the perspective of the Bulgarian National Health Insurance Fund. Cost-effectiveness was analysed over a 1-year time horizon using data from clinical trials. The incremental cost-effectiveness ratio (ICER) was the main outcome measure.

Results

In Bulgaria, degludec was highly cost-effective versus glargine U100 in people with T1DM and T2DM. The ICERs were estimated to be 4493.68 BGN/quality-adjusted life year (QALY) in T1DM, 399.11 BGN/QALY in T2DM on basal oral therapy (T2DMBOT) and 7365.22 BGN/QALY in T2DM on basal bolus therapy (T2DMB/B), which are below the cost-effectiveness threshold of 39,619 BGN in Bulgaria. Degludec was associated with higher insulin costs in all three patient groups; however, savings from a reduction in hypoglycaemic events with degludec versus glargine U100 partially offset these costs. Sensitivity analysis demonstrated that the results were robust and largely insensitive to variations in input parameters. At a willingness-to-pay threshold of 39,619 BGN/QALY, the probability of degludec being cost-effective versus glargine U100 was 60.0% in T1DM, 99.4% in T2DMBOT and 91.3% in T2DMB/B.

Conclusion

Degludec is a cost-effective alternative to biosimilar glargine U100 for patients with T1DM and T2DM in Bulgaria. Degludec could be of particular benefit to those patients suffering recurrent hypoglycaemia and those who require additional flexibility in the dosing of insulin.
Benchmarking nurse outcomes in Australian Magnet® hospitals: cross-sectional survey
Authors: Stone L. , Arneil M. , Coventry L. , Casey V. , Moss S. , Cavadino A. , Laing B. , McCarthy AL
Published: December 2019

Background

Positive reports of nursing-related outcomes such as quality nursing care, nursing engagement with work and good practice environment are crucial in attaining and maintaining Magnet® designation. The majority of Magnet®-designated organisations (N = 482) are in the USA, with their aggregate nursing outcomes widely published as benchmark data. Australian Magnet® outcomes have not been aggregated or published to date.

Methods

The aims are to benchmark educational preparation, occupational burnout, job satisfaction, intention to leave and working environment of nurses in Australian Magnet®-designated facilities and to determine the reliability of the Practice Environment Scale-Australia.

The design is a cross-sectional multisite survey set in all three Australian Magnet®-designated organisations.

The demographics included age, gender, level of education, years in practice, level of seniority and position title. Two items measured job satisfaction and intent to stay in current employment. The Maslach Burnout Inventory explored the three domains of nursing engagement: depersonalisation, personal achievement and emotional exhaustion. The Australian version of the Practice Environment Scale interrogated participants’ perceptions of their work environments.

Results

2004 nurses participated (response rate 45.9%). Respondents’ mean age was 39.2 years (range 20–72). They were predominantly female and had worked in their current facility for more than 5 years. Eighty five percent had a minimum of a Bachelor’s degree. Eighty-six percent of respondents were satisfied or very satisfied with their current position. Eighty eight percent had no intention of leaving their current employer within the next 12 months. Participants rated their hospitals highly in all domains of the practice environment. Respondents reported less burnout in the personal accomplishment and depersonalisation domains than in the emotional exhaustion domain, in which they reported average levels of burnout. The internal consistency of the Practice Environment Scale-Australia was confirmed in this sample (Cronbach α’s 0.87–0.9 for subscales and 0.89 for composite score).

Conclusion

In this paper, we present nursing outcome data from all Australian Magnet® hospitals for the first time. This provides a benchmark that facilitates comparison with nursing outcomes published by Australian non-Magnet® hospitals and with international Magnet® organisations.
Barriers to nurse–patient communication in Saudi Arabia: an integrative review
Authors: Alshammari Mukhlid , Duff Jed , Guilhermino Michelle
Published: December 2019

Background

Effective nurse–patient communication is important in improving quality of health care. However, there are several barriers to nurse–patient communication in Saudi Arabia. This is attributed to the increasing number of non-Saudi expatriate nurses providing health care to patients. In particular, there are differences in culture, religion and language among non-Saudi nurses and patients. This integrative review aims to identify and synthesize quantitative and qualitative evidence on the current practice in nurse–patient communication in Saudi Arabia and its effect on service users’ quality of care, safety and satisfaction.

Methods

An integrative review based on Whittemore and Knafl’s approach (Whittemore and Knafl, J Adv Nurs 52:546–553, 2005) was used to conduct the review. Peer-reviewed articles containing any of a series of specific key terms were identified from sources such as CINAHL, EMBASE, Medline, PubMed and PsychINFO. The review included studies that focused on nurse–patient communication issues, communication barriers, and cultural and language issues. The search was limited to papers about the Saudi Arabian health system published in English and Arabic languages between 2000 and 2018. A data extraction form was developed to extract information from included articles.

Results

Twenty papers were included in the review (Table 1). Ten papers employed quantitative methods, eight papers used qualitative methods and two used mixed methods. The review revealed two major themes: ‘current communication practices’ and ‘the effect of communication on patients’. Some of the communication practices rely on non-verbal methods due to a lack of a common language, which often results in the meaning of the communication being misinterpreted. Many non-Saudi nurses have limited knowledge about Saudi culture and experience difficulty in understanding, and in some cases respecting, the cultural and religious practices of patients. Further, limited nurse–patient communication impacts negatively on the nurse–patient relationship, which can affect patient safety and lead to poor patient satisfaction.

Conclusions

Current nurse–patient communication practices do not meet the needs of Saudi patients due to cultural, religious and language differences between nurses and patients. The barriers to effective nurse–patient communication adversely effects patient safety and patient satisfaction. Further research from the perspective of the patient and family is needed.
Developing an adapted Charlson comorbidity index for ischemic stroke outcome studies
Authors: Hall Ruth E. , Porter Joan , Quan Hude , Reeves Mathew J.
Published: December 2019

Background

The Charlson comorbidity index (CCI) is commonly used to adjust for patient casemix. We reevaluated the CCI in an ischemic stroke (IS) cohort to determine whether the original seventeen comorbidities and their weights are relevant.

Methods

We identified an IS cohort (N = 6988) from the Ontario Stroke Registry (OSR) who were discharged from acute hospitals (N = 100) between April 1, 2012 and March 31, 2013. We used hospital discharge ICD-10-CA data to identify Charlson comorbidities. We developed a multivariable Cox model to predict one-year mortality retaining statistically significant (P < 0.05) comorbidities with hazard ratios ≥1.2. Hazard ratios were used to generate revised weights (1–6) for the comorbid conditions. The performance of the IS adapted Charlson comorbidity index (ISCCI) mortality model was compared to the original CCI using the c-statistic and continuous Net Reclassification Index (cNRI).

Results

Ten of the 17 Charlson comorbid conditions were retained in the ISCCI model and 7 had reassigned weights when compared to the original CCI model . The ISCCI model showed a small but significant increase in the c-statistic compared to the CCI for 30-day mortality (c-statistic 0.746 vs. 0.732, p = 0.009), but no significant increase in c-statistic for in-hospital or one-year mortality. There was also no improvement in the cNRI when the ISCCI model was compared to the CCI.

Conclusions

The ISCCI model had similar performance to the original CCI model. The key advantage of the ISCCI model is it includes seven fewer comorbidities and therefore easier to implement in situations where coded data is unavailable.
Validation of use of billing codes for identifying telemedicine encounters in administrative data
Authors: Yeramosu Deepika , Kwok Florence , Kahn Jeremy M. , Ray Kristin N.
Published: December 2019

Background

Telemedicine is the use of telecommunication technology to remotely provide healthcare services. Evaluation of telemedicine use often relies on administrative data, but the validity of identifying telemedicine encounters in administrative data is not known. The objective of this study was to assess the accuracy of billing codes for identifying telemedicine use.

Methods

In this retrospective study of encounters within a large integrated health system from January 2016 to December 2017, we examined the accuracy of billing codes for identifying live-interactive and store-and-forward telemedicine encounters compared to manual chart review. To further examine external validity, we applied these codes and assessed patient and visit characteristics for identified live-interactive telemedicine encounters and store-and-forward telemedicine encounters in a second data set.

Results

In manual review of 390 encounters, 75 encounters were live-interactive telemedicine and 158 were store-and-forward telemedicine. In weighted analysis, the presence of the GT modifier in the absence of the GQ modifier or CPT code 99444 yielded 100% sensitivity and 99.99% specificity for identification of live-interactive telemedicine encounters. The presence of either the GQ modifier or the CPT code 99444 had 100% sensitivity and 100% specificity for identification of store-and-forward telemedicine encounters. Applying these algorithms to a second data set (n = 5,917,555) identified telemedicine encounters with expected patient and visit characteristics.

Conclusions

These findings provide support for use of CPT codes to perform telemedicine research in administrative data, aiding ongoing work to understand the role of non-face-to-face care in optimizing health care delivery.
Does a tailored intervention to promote adherence in patients with chronic lung disease affect exacerbations? A randomized controlled trial
Authors: Gregoriano Claudia , Dieterle Thomas , Breitenstein Anna-Lisa , Dürr Selina , Baum Amanda , Giezendanner Stéphanie , Maier Sabrina , Leuppi-Taegtmeyer Anne , Arnet Isabelle , Hersberger Kurt E. , Leuppi Jörg D.
Published: December 2019

Background

Poor medication-adherence is common in chronic lung patients, resulting in reduced health-outcomes and increased healthcare-costs. This study aimed to investigate the impact of an acoustic reminder and support calls on adherence to inhaled therapy in asthma and COPD patients and to determine their effect on exacerbations.

Methods

This single-blinded randomized controlled trial investigated asthma and COPD patients during 6 months in an ambulatory setting. The intervention consisted of daily alarm clock and support phone calls, whenever use of rescue medication doubled or inhaled medication was not taken as prescribed. Primary outcome was time to next exacerbation. Frequency of exacerbations, adherence to inhaled medication and quality of life scores were secondary outcomes. Cox and Poisson regression were used to determine intervention effect on time to exacerbation and frequency of exacerbations, respectively.

Results

Seventy-five participants were assigned to the intervention group and 74 to usual follow-up care. During a median follow-up of 6.2 months, 22 and 28% in the intervention and control groups respectively, experienced at least one exacerbation. Intervention had no effect on time to first exacerbation (HR 0.65, 95% CI 0.21 to 2.07,P = .24), but showed a trend toward a 39% decreased frequency of exacerbations (RR = 0.61, 95% CI 0.35 to 1.03,P = .070) for the adjusted models, respectively. The intervention group had significantly more days with 80–100% taking adherence regarding puff inhalers (82 ± 14% vs. 60 ± 30%,P < .001) and dry powder capsules (90 ± .10% vs. 80 ± 21%,P = .01). Timing adherence in participants using puff inhalers was higher in the intervention group (69 ± 25% vs. 51 ± 33%,P < .001). No significant differences in QoL were found between the two groups.

Conclusion

Participants assigned to the intervention group had significantly better taking and timing adherence of inhaled medication resulting in a trend towards a decreased frequency of exacerbations. However, no effect on time to next exacerbation was observed.

Trial registration

ClinicalTrials.gov:NCT02386722, Registered 14 February 2014.
Green pyomelanin-mediated synthesis of gold nanoparticles: modelling and design, physico-chemical and biological characteristics
Authors: Ben Tahar Imen , Fickers Patrick , Dziedzic Andrzej , Płoch Dariusz , Skóra Bartosz , Kus-Liśkiewicz Małgorzata
Published: December 2019

Background

Synthesis of nanoparticles (NPs) and their incorporation in materials are amongst the most studied topics in chemistry, physics and material science. Gold NPs have applications in medicine due to their antibacterial and anticancer activities, in biomedical imaging and diagnostic test. Despite chemical synthesis of NPs are well characterized and controlled, they rely on the utilization of harsh chemical conditions and organic solvent and generate toxic residues. Therefore, greener and more sustainable alternative methods for NPs synthesis have been developed recently. These methods use microorganisms, mainly yeast or yeast cell extract. NPs synthesis with culture supernatants are most of the time the preferred method since it facilitates the purification scheme for the recovery of the NPs. Extraction of NPs, formed within the cells or cell-wall, is laborious, time-consuming and are not cost effective. The bioactivities of NPs, namely antimicrobial and anticancer, are known to be related to NPs shape, size and size distribution.

Results

Herein, we reported on the green synthesis of gold nanoparticles (AuNPs) mediated by pyomelanin purified from the yeast Yarrowia lipolytica. A three levels four factorial Box–Behnken Design (BBD) was used to evaluate the influence of temperature, pH, gold salt and pyomelanin concentration on the nanoparticle size distribution. Based on the BBD, a quadratic model was established and was applied to predict the experimental parameters that yield to AuNPs with specific size. The synthesized nanoparticles with median size value of 104 nm were of nanocrystalline structure, mostly polygonal or spherical. They exhibited a high colloidal stability with zeta potential of − 28.96 mV and a moderate polydispersity index of 0.267. The absence of cytotoxicity of the AuNPs was investigated on two mammalian cell lines, namely mouse fibroblasts (NIH3T3) and human osteosarcoma cells (U2OS). Cell viability was only reduced at AuNPs concentration higher than 160 µg/mL. Moreover, they did not affect on the cell morphology.

Conclusion

Our results indicate that different process parameters affect significantly nanoparticles size however with the mathematical model it is possible to define the size of AuNPs. Moreover, this melanin-based gold nanoparticles showed neither cytotoxicity effect nor altered cell morphology.
KCNQ1OT1 aggravates cell proliferation and migration in bladder cancer through modulating miR-145-5p/PCBP2 axis
Authors: Wang Jingyu , Zhang Hao , Situ Jie , Li Mingzhao , Sun Hua
Published: December 2019

Background

The large involvement of long non-coding RNAs (LncRNAs) in the biological progression of numerous cancers has been reported. The function of lncRNA KCNQ1OT1 in bladder cancer (BC) remains largely unknown. This study aimed to explore the critical role of KCNQ1OT1 in BC.

Materials and methods

The qRT-PCR was applied to test the expression of RNAs. Cell proliferation was detected by CCK-8 and colony formation assays. Cell apoptosis was measured by TUNEL and flow cytometry experiments. Wound healing and transwell assays were employed to evaluate cell migration and invasion ability respectively. Western blot assay was used to measure relevant protein expression. Immunofluorescence (IF) staining was used to observe EMT process in BC.

Results

KCNQ1OT1 was significantly overexpressed in BC tissue and cell lines. KCNQ1OT1 depletion repressed cell proliferation, migration and invasion, whereas encouraged cell apoptosis. KCNQ1OT1 was a negatively/positively correlated with miR-145-5p/PCBP2 in respect with expression. Mechanically, KCNQ1OT1 was sponge of miR-145-5p and up-regulated the expression of PCBP2. MiR-145-5p inhibition and PCBP2 up-regulation could countervail the tumor-inhibitor role of KCNQ1OT1 knockdown in BC.

Conclusion

KCNQ1OT1 serves as competing endogenous RNA (ceRNA) to up-regulate PCBP2 via sponging miR-145-5p in BC progression.
SKA1 promotes malignant phenotype and progression of glioma via multiple signaling pathways
Authors: Wang Xizhao , Zeng Yu , Zhou Mingfeng , Zhang Xian , Xu Anqi , Lin Jie , Wu Zhiyong , Xie Cheng , Luo Jie , Ding Shengfeng , Zhan Zhengming , Long Hao , Song Ye
Published: December 2019

Background

Spindle and kinetochore associated protein 1 (SKA1) is a protein involved in chromosome congression and mitosis. It has been found to be upregulated and oncogenic in several human cancers. Herein, we investigated the precise role of SKA1 in the progression and malignant phenotype of human glioma.

Methods

Bioinformatic analysis was carried out based on the RNA-seq data and corresponding clinical data from GEO, TCGA and CGGA databases. Western blot was performed to analyze the expression of SKA1 in clinical samples and signaling pathway proteins in glioma cells, respectively. CCK8 assay, colony forming assay and EdU assay were performed to assess the cell viability. Cell migration and invasion assays were also performed. Moreover, xenograft model was established and the expression of SKA1 was assessed in the xenograft by immunohistochemistry.

Results

SKA1 expression is positively correlated with glioma grade and could be a promising biomarker for GBM. Moreover, overexpression of SKA1 may lead to poor prognosis in glioma. Downregulation of SKA1 attenuated cell viability, migration, and invasion in U251, U87, LN229 and T98 cells. Furthermore, GSEA analysis demonstrated that SKA1 was involved in the cell cycle, EMT pathway as well as Wnt/β-catenin signaling pathway, which were then confirmed with Western blot analysis.

Conclusion

SKA1 promotes malignant phenotype and progression of glioma via multiple pathways, including cell cycle, EMT, Wnt/β-catenin signaling pathway. Therefore, SKA1 could be a promising therapeutic target for the treatment of human gliomas.
Biology and bionomics of malaria vectors in India: existing information and what more needs to be known for strategizing elimination of malaria
Authors: Subbarao Sarala K. , Nanda Nutan , Rahi Manju , Raghavendra Kamaraju
Published: December 2019

India has committed to eliminate malaria by 2030. The national framework for malaria elimination released by the Government of India plans to achieve this goal through strategic planning in a phased manner. Since vector control is a major component of disease management and vector elimination, it requires a thorough understanding of the biology and bionomics of malaria vectors exhibiting definite distribution patterns in diverse ecosystems in the country. Although a wealth of information is available on these aspects, lesser-known data are on biting time and rhythm, and the magnitude of outdoor transmission by the vectors which are crucial for effective implementation of the key vector control interventions. Most of the data available for the vector species are at sensu lato level, while the major vectors are species complexes and their members distinctly differ in biological characters. Furthermore, the persistent use of insecticides in indoor residual spray and long-lasting insecticidal nets has resulted in widespread resistance in vectors and changes in their behaviour. In this document, challenges in vector control in the Indian context have been identified and possible solutions to overcome the problem are suggested. Adequate addressing of the issues raised would greatly help make a deep dent in malaria transmission and consequently result in disease elimination within the targeted time frame.
Micromechanical modeling of the contact stiffness of an osseointegrated bone–implant interface
Authors: Raffa Maria Letizia , Nguyen Vu-Hieu , Haiat Guillaume
Published: December 2019

Background

The surgical success of cementless implants is determined by the evolution of the biomechanical properties of the bone–implant interface (BII). One difficulty to model the biomechanical behavior of the BII comes from the implant surface roughness and from the partial contact between bone tissue and the implant. The determination of the constitutive law of the BII would be of interest in the context of implant finite element (FE) modeling to take into account the imperfect characteristics of the BII. The aim of the present study is to determine an effective contact stiffness$$\left( {K_{c}^{\text{FEM}} } \right)$$KcFEMof an osseointegrated BII accounting for its micromechanical features such as surface roughness, bone–implant contact ratio (BIC) and periprosthetic bone properties. To do so, a 2D FE model of the BII under normal contact conditions was developed and was used to determine the behavior of$$K_{c}^{\text{FEM}}$$KcFEM.

Results

The model is validated by comparison with three analytical schemes based on micromechanical homogenization including two Lekesiz’s models (considering interacting and non-interacting micro-cracks) and a Kachanov’s model.$$K_{c}^{\text{FEM}}$$KcFEMis found to be comprised between 1013and 1015 N/m3according to the properties of the BII.$$K_{c}^{\text{FEM}}$$KcFEMis shown to increase nonlinearly as a function of the BIC and to decrease as a function of the roughness amplitude for high BIC values (above around 20%). Moreover,$$K_{c}^{\text{FEM}}$$KcFEMdecreases as a function of the roughness wavelength and increases linearly as a function of the Young’s modulus of periprosthetic bone tissue.

Conclusions

These results open new paths in implant biomechanical modeling since this model may be used in future macroscopic finite element models modeling the bone–implant system to replace perfectly rigid BII conditions.
The differential effects of fatty acids on enterocytic abundance of amyloid-beta
Authors: Galloway Susan , Takechi Ryusuke , Nesbit Michael , Pallebage-Gamarallage Menuka M. , Lam Virginie , Mamo John C. L.
Published: December 2019

Background

Consumption of a Western-styled diet enriched in saturated fatty acids (SFA) relative to polyunsaturated fatty acids is positively associated with risk for Alzheimer’s disease. Whilst potential causal mechanism are unclear, there is increasing evidence that chronic ingestion of SFA enriched diets promote increase the plasma levels of lipoprotein-associated amyloid-β (Aβ). However, the effects of dietary mono- and poly-unsaturated fats (MUFA/PUFA) on nascent lipoprotein Aβ abundance have not been previously reported.

Methods

Wild-type C57BL/6 J mice were maintained on low-fat control chow (LF) or diets enriched in either SFA, MUFA, or PUFA for 9 months. Enterocytic abundance of Aβ was determined with quantitative immunofluorescent microscopy and plasma Aβ was measured by ELISA.

Results

The chronic ingestion of SFA-enriched diet increased the enterocytic abundance and plasma concentration of Aβ compared to LF control mice. The mice maintained on MUFA or PUFA diet showed comparable enterocytic and plasma Aβ levels to the LF control mice.

Conclusions

The data indicates that a diet enriched in SFA significantly increases the enterocytic Aβ production and secretion into the circulation, whilst MUFA and PUFA enriched diet do not exert such effects.
Comparison of the prognostic values of three calculation methods for echocardiographic relative wall thickness in acute decompensated heart failure
Authors: Yamaguchi Satoshi , Shimabukuro Michio , Abe Masami , Arakaki Tomohiro , Arasaki Osamu , Ueda Shinichiro
Published: December 2019

Purpose

Left ventricular (LV) wall thickness can be measured at the posterior wall (PW) and the intraventricular septum (IVS) in a parasternal long axis view by transthoracic echocardiography. Thus, there are three methods to calculate relative wall thickness as follows: RWTPW = 2 × PWth/LVDd; RWTIVS + PW = (IVSth + PWth) /LVDd; and RWTIVS = 2 × IVSth/LVDd (IVSth = interventricular septum thickness; LVDd = LV internal dimension at end--diastole; PWth = posterior wall thickness). The aim was to compare the prognostic values of these RWTs in patients with acute decompensated heart failure (ADHF).

Method

This was a single-center, retrospective, observational study at a Japanese community hospital. A total of 389 hospitalized ADHF patients were divided into two groups based on the three median RWT values. The primary outcome was all-cause death. Survival analysis was performed, and Cox proportional hazard models unadjusted and adjusted by Get With The Guideline score were used.

Results

High-RWTPW had poor survival (log-rank, P = 0.009) and was a significant risk (unadjusted HR (95%CI), 1.72 (1.14–2.61), P = 0.01; adjusted HR, 1.95 (1.28–2.98), P = 0.02). High-RWTIVS + PW was not associated with poor survival on survival analysis or the unadjusted Cox model. Only the adjusted Cox model showed that High-RWTIVS + PW was associated with a significant risk of the primary outcome (unadjusted HR (95%CI), 1.45 (0.96–2.17), P = 0.07; adjusted HR, 1.53 (1.01–2.32), P = 0.045). High-RWTIVS did not have significant prognostic value.

Conclusions

When calculating RWT, RWTPW should be recommended for evaluating the mortality risk in ADHF.
Cardiopulmonary exercise testing and echocardiographic exam: an useful interaction
Authors: Santoro Ciro , Sorrentino Regina , Esposito Roberta , Lembo Maria , Capone Valentina , Rozza Francesco , Romano Massimo , Trimarco Bruno , Galderisi Maurizio
Published: December 2019

Cardiopulmonary exercise test (CPET) is a functional assessment that helps to detect disorders affecting the system involved in oxygen transport and utilization through the analysis of the gas exchange during exercise. The clinical application of CPET is various, it including training prescription, evaluation of treatment efficacy and outcome prediction in a broad spectrum of conditions. Furthermore, in patients with shortness of breath it provides pivotal information to bring out an accurate differential diagnosis between physical deconditioning, cardiopulmonary disease and muscular diseases. Modern software allows the breath-by-breath analysis of the volume of oxygen intake (VO2), volume of carbon dioxide output (VCO2) and expired air (VE). Through this analysis, CPET provides a series of additional parameters (peak VO2, ventilatory threshold, VE/VCO2 slope, end-tidal carbon dioxide exhaled) that characterize different patterns, helping in diagnosis process. Limitations to the routine use of CPET are mainly represented from the lack of measurement standardization and limited data from randomized multicentric studies. The integration of CPET with exercise stress echocardiography has been recently introduced in the clinical practice by integrating the diagnostic power offered by both the tools. This combined approach has been demonstrated to be valuable for diagnosing several cardiac diseases, including heart failure with preserved or reduced ejection fraction, cardiomyopathies, pulmonary arterial hypertension, valvular heart disease and coronary artery disease. Future investigations are needed to further promote this intriguing combination in the clinical and research setting.
Chaperone activity of serine protease HtrA of Helicobacter pylori as a crucial survival factor under stress conditions
Authors: Zarzecka Urszula , Harrer Aileen , Zawilak-Pawlik Anna , Skorko-Glonek Joanna , Backert Steffen
Published: December 2019

Background

Serine protease HtrA exhibits both proteolytic and chaperone activities, which are involved in cellular protein quality control. Moreover, HtrA is an important virulence factor in many pathogens including Helicobacter pylori, for which the crucial stage of infection is the cleavage of E-cadherin and other cell-to-cell junction proteins.

Methods

The in vitro study of H. pylori HtrA (HtrAHp) chaperone activity was carried out using light scattering assays and investigation of lysozyme protein aggregates. We produced H. pylori ∆htrA deletion and HtrAHp point mutants without proteolytic activity in strain N6 and investigated the survival of the bacteria under thermal, osmotic, acidic and general stress conditions as well as the presence of puromycin or metronidazole using serial dilution tests and disk diffusion method. The levels of cellular and secreted proteins were examined using biochemical fraction and Western blotting. We also studied the proteolytic activity of secreted HtrAHp using zymography and the enzymatic digestion of β-casein. Finally, the consequences of E-cadherin cleavage were determined by immunofluorescence microscopy.

Results

We demonstrate that HtrAHp displays chaperone activity that inhibits the aggregation of lysozyme and is stable under various pH and temperature conditions. Next, we could show that N6 expressing only HtrA chaperone activity grow well under thermal, pH and osmotic stress conditions, and in the presence of puromycin or metronidazole. In contrast, in the absence of the entire htrA gene the bacterium was more sensitive to a number of stresses. Analysing the level of cellular and secreted proteins, we noted that H. pylori lacking the proteolytic activity of HtrA display reduced levels of secreted HtrA. Moreover, we compared the amounts of secreted HtrA from several clinical H. pylori strains and digestion of β-casein. We also demonstrated a significant effect of the HtrAHp variants during infection of human epithelial cells and for E-cadherin cleavage.

Conclusion

Here we identified the chaperone activity of the HtrAHp protein and have proven that this activity is important and sufficient for the survival of H. pylori under multiple stress conditions. We also pinpointed the importance of HtrAHp chaperone activity for E- cadherin degradation and therefore for the virulence of this eminent pathogen.
Identification of key genes in invasive clinically non-functioning pituitary adenoma by integrating analysis of DNA methylation and mRNA expression profiles
Authors: Cheng Sen , Xie Weiyan , Miao Yazhou , Guo Jing , Wang Jichao , Li Chuzhong , Zhang Yazhuo
Published: December 2019

Background

Tumor surrounding the internal carotid artery or invading to the cavernous sinus is an important characteristic of invasive pituitary adenoma, and a pivotal factor of tumor residue and regrowth. Without specific changes in serum hormone related to the adenohypophyseal cell of origin, clinically non-functioning pituitary adenoma is more likely to be diagnosed at invasive stages compared with functioning pituitary adenoma. The underlying mechanism of tumor invasion remains unknown. In this study, we aimed to identify key genes in tumor invasion by integrating analyses of DNA methylation and gene expression profiles.

Method

Genome-wide DNA methylation and mRNA microarray analysis were performed for tumor samples from 68 patients at the Beijing Tiantan Hospital. Differentially expressed genes and methylated probes were identified based on an invasive vs non-invasive grouping. Differentially methylated probes in the promoter region of targeted genes were assessed. Pearson correlation analysis was used to identify genes with a strong association between DNA methylation status and expression levels. Pyrosequencing and RT-PCR were used to validate the methylation status and expression levels of candidate genes, respectively.

Results

A total of 8842 differentially methylated probes, located on 4582 genes, and 661 differentially expressed genes were identified. Both promoter methylation and expression alterations were observed for 115 genes with 58 genes showing a negative correlation between DNA methylation status and expression level. Nineteen genes that exhibited notably negative correlations between DNA methylation and gene expression levels, are involved in various gene ontologies and pathways, or played an important role in different diseases, were regarded as candidate genes. We found an increased methylation with a decreased expression of PHYHD1, LTBR, C22orf42, PRR5, ANKDD1A, RAB13, CAMKV, KIFC3, WNT4 and STAT6, and a decreased methylation with an increased expression of MYBPHL. The methylation status and expression levels of these genes were validated by pyrosequencing and RT-PCR.

Conclusions

The DNA methylation and expression levels of PHYHD1, LTBR, MYBPHL, C22orf42, PRR5, ANKDD1A, RAB13, CAMKV, KIFC3, WNT4 and STAT6 are associated with tumor invasion, and these genes may become the potential genes for targeted therapy.
IgA1 deposition may induce NLRP3 expression and macrophage transdifferentiation of podocyte in IgA nephropathy
Authors: Peng Wei , Pei Gai-qin , Tang Yi , Tan Li , Qin Wei
Published: December 2019

Background

The NLRP3 inflammasome plays an important role in mediating podocyte injury in various kidney diseases. The aim of this study was to investigate whether NLRP3 expression associated with podocyte injury was involved in the pathogenesis of IgA nephropathy (IgAN).

Methods

NLRP3 inflammasomes and macrophage marker (F4/80) were detected in the renal tissues of IgAN patients. Association between kidney NLRP3 levels and the clinical feature of IgAN patients was analyzed. Podocytes were incubated with serum containing dys-glycosylated IgA1 protein isolated from IgAN patients. Expression of NLRP3 inflammasomes, F4/80, inflammatory cytokine and renal fibrosis marker were measured using RT-PCR and Western blotting.

Results

Renal NLRP3 inflammasome expression was significantly increased in IgAN patients compared to normal control tissues. Moreover, co-expression of NLRP3 and F4/80 could be observed in the podocytes of IgAN patients. Patients with eGFR < 60 ml/min/1.73 m2 had remarkably higher tubular NLRP3 expression (P < 0.05), while patients with gross proteinuria (≥ 3.5 g/day) had a significantly higher glomerular NLRP3 expression (P < 0.05). Further analysis indicated that dys-glycosylated IgA1 isolated from IgAN patient serum could induce podocyte expression of NLRP3 and the macrophage marker F4/80, which could lead to induction of an inflammatory reaction (increased expression of ICAM-1) and fibrosis (increased expression of α-SMA).

Conclusion

Dys-glycosylated IgA1 isolated from IgAN patient serum could induce NLRP3 expression in podocytes and initiate podocyte macrophage transdifferentiation (PMT). After PMT, podocytes secrete proinflammatory cytokines that can contribute to the inflammation cascade and renal fibrosis changes associated with IgAN.
Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry
Authors: Yuan Chen , Wang Jia-Ye , Zhao Hai-Jiao , Li Yan , Li Di , Ling Hong , Zhuang Min
Published: December 2019

Background

Peptides corresponding to N- and C-terminal heptad repeat regions (HR1 and HR2, respectively) of gp41 can inhibit HIV-1 infection in a dominant negative manner by interfering with refolding of the viral HR1 and HR2 to form a six-helix bundle (6HB) that induces fusion between viral and host cell membranes. Previously, we found that HIV-1 acquired the mutations of Glu560 (E560) in HR1 of envelope (Env) to escape peptide inhibitors. The present study aimed to elucidate the critical role of position 560 in the virus entry and potential resistance mechanisms.

Results

The Glu560Lys/Asp/Gly (E560K/D/G) mutations in HR1 of gp41 that are selected under the pressure of N- and C-peptide inhibitors modified its molecular interactions with HR2 to change 6HB stability and peptide inhibitor binding. E560K mutation increased 6HB thermostability and resulted in resistance to N peptide inhibitors, but E560G or E560D as compensatory mutations destabilized the 6HB to reduce inhibitor binding and resulted in increased resistance to C peptide inhibitor, T20. Significantly, the neutralizing activities of all mutants to soluble CD4 and broadly neutralizing antibodies targeting membrane proximal external region, 2F5 and 4E10 were improved, indicating the mutations of E560 could regulate Env conformations through cross interactions with gp120 or gp41. The molecular modeling analysis of E560K/D/G mutants suggested that position 560 might interact with the residues within two potentially flexible topological layer 1 and layer 2 in the gp120 inner domain to apparently affect the CD4 utilization. The E560K/D/G mutations changed its interactions with Gln650 (Q650) in HR2 to contribute to the resistance of peptide inhibitors.

Conclusions

These findings identify the contributions of mutations of E560K/D/G in the highly conserved gp41 and highlight Env’s high degree of plasticity for virus entry and inhibitor design.
Structured medical electives: a concept whose time has come?
Authors: Willott Chris , Khair Eva , Worthington Roger , Daniels Katy , Clarfield A. Mark
Published: December 2019

Background

Most international electives in which medical students from high-income countries travel abroad are largely unstructured, and can lead to problematic outcomes for students as well as sending and receiving institutions. We analyse the problems of unstructured medical electives and describe the benefits of an elective experience that includes more organisation and oversight from the sending medical school.

Results

A number of structured elective programmes have been developed, including those at the Medical School for International Health, Israel and the University of Dundee, United Kingdom. These programmes provide significant pre-departure training in global health and the ethical dimensions of electives, support and monitoring during the elective, and post-elective debrief. Crucially, the programmes themselves are developed on the basis of long-term engagement between institutions, and have an element of reciprocity.

We further identify two major problems in current medical electives: the different ethical contexts in which electives take place, and the problem of ‘voluntourism’, in which the primary beneficiary of the activity is the medical student, rather than the receiving institution or health system. These two issues should be seen in the light of unequal relations between sending and receiving institutions, which largely mirror unequal relations between the Global North and South.

Conclusion

We argue that more structured elective programmes could form a useful corrective to some of the problems identified with medical electives. We recommend that medical schools in countries such as the UK strongly consider developing these types of programmes, and if this is not possible, they should seek to further develop their pre-departure training curricula.
Association between single-nucleotide polymorphisms within candidate genes and fertility in Landrace and Duroc pigs
Authors: Tremoen Nina Hårdnes , Van Son Maren , Andersen-Ranberg Ina , Grindflek Eli , Myromslien Frøydis Deinboll , Gaustad Ann Helen , Våge Dag Inge
Published: December 2019

Finding effective predictors of traits related to boar fertility is essential for increasing the efficiency of artificial insemination systems in pig breeding. The objective of this study was to find associations between single-nucleotide polymorphisms (SNPs) within candidate genes and fertility in the breeds Landrace and Duroc. Animals with breeding values for total number of piglets born, were re-sequenced for exonic regions of 14 candidate genes related to male and female fertility using samples from 16 Landrace boars and 16 Duroc boars (four with high and four with low breeding value of total number of piglets born for each breed for male fertility, and the same for female fertility) to detect genetic variants. Genotyping for the detected SNPs was done in 619 Landrace boars and 513 Duroc boars. Two SNPs in BMPR1 and one SNP in COX-2 were found significantly associated with the total number of piglets born in Landrace. In Duroc, two SNPs in PLCz, one SNP in VWF and one SNP in ZP3 were found significantly associated with total number of piglets born. These SNPs explained between 0.27% and 1.18% of the genetic variance. These effects are too low for being used directly for selection purposes but can be of interest in SNP-panels used for genomic selection.