bluuebunny/crossref_metadata_2025 huggingface dataset:
Localising occult prostate cancer metastasis with advanced imaging techniques (LOCATE trial): a prospective cohort, observational diagnostic accuracy trial investigating whole–body magnetic resonance imaging in radio-recurrent prostate cancer
Authors: Adeleke Sola , Latifoltojar Arash , Sidhu Harbir , Galazi Myria , Shah Taimur T. , Clemente Joey , Davda Reena , Payne Heather Ann , Chouhan Manil D. , Lioumi Maria , Chua Sue , Freeman Alex , Rodriguez-Justo Manuel , Coolen Anthony , Vadgama Sachin , Morris Steve , Cook Gary J. , Bomanji Jamshed , Arya Manit , Chowdhury Simon , Wan Simon , Haroon Athar , Ng Tony , Ahmed Hashim Uddin , Punwani Shonit
Published: November 2019

Background

Accurate whole-body staging following biochemical relapse in prostate cancer is vital in determining the optimum disease management. Current imaging guidelines recommend various imaging platforms such as computed tomography (CT), Technetium 99 m (99mTc) bone scan and 18F-choline and recently 68Ga-PSMA positron emission tomography (PET) for the evaluation of the extent of disease. Such approach requires multiple hospital attendances and can be time and resource intensive. Recently, whole-body magnetic resonance imaging (WB-MRI) has been used in a single visit scanning session for several malignancies, including prostate cancer, with promising results, providing similar accuracy compared to the combined conventional imaging techniques. The LOCATE trial aims to investigate the application of WB-MRI for re-staging of patients with biochemical relapse (BCR) following external beam radiotherapy and brachytherapy in patients with prostate cancer.

Methods/design

The LOCATE trial is a prospective cohort, multi-centre, non-randomised, diagnostic accuracy study comparing WB-MRI and conventional imaging. Eligible patients will undergo WB-MRI in addition to conventional imaging investigations at the time of BCR and will be asked to attend a second WB-MRI exam, 12-months following the initial scan. WB-MRI results will be compared to an enhanced reference standard comprising all the initial, follow-up imaging and non-imaging investigations. The diagnostic performance (sensitivity and specificity analysis) of WB-MRI for re-staging of BCR will be investigated against the enhanced reference standard on a per-patient basis. An economic analysis of WB-MRI compared to conventional imaging pathways will be performed to inform the cost-effectiveness of the WB-MRI imaging pathway. Additionally, an exploratory sub-study will be performed on blood samples and exosome-derived human epidermal growth factor receptor (HER) dimer measurements will be taken to investigate its significance in this cohort.

Discussion

The LOCATE trial will compare WB-MRI versus the conventional imaging pathway including its cost-effectiveness, therefore informing the most accurate and efficient imaging pathway.

Trial registration

LOCATE trial was registered on ClinicalTrial.gov on 18th of October 2016 with registration reference number NCT02935816.
Vitamin e-loaded membrane dialyzers reduce hemodialysis inflammaging
Authors: Sepe Vincenzo , Gregorini Marilena , Rampino Teresa , Esposito Pasquale , Coppo Rosanna , Galli Francesco , Libetta Carmelo
Published: November 2019

Background

Inflammaging is a persistent, low−grade, sterile, nonresolving inflammatory state, associated with the senescence of the immune system. Such condition downregulates both innate and adaptive immune responses during chronic disorders as type II diabetes, cancer and hemodialysis, accounting for their susceptibility to infections, malignancy and resistance to vaccination.

Aim of this study was to investigate hemodialysis inflammaging, by evaluating changes of several hemodialysis treatments on indoleamine 2,3-dioxygenase-1 activity and nitric oxide formation.

Methods

We conducted a randomized controlled observational crossover trial. Eighteen hemodialysis patients were treated with 3 different hemodialysis procedures respectively: 1) Low−flux bicarbonate hemodialysis, 2) Low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers, and 3) Hemodialfitration. The control group consisted of 14 hospital staff healthy volunteers. Blood samples were collected from all 18 hemodialysis patients just after the long interdialytic interval, at the end of each hemodialysis treatment period.

Results

Hemodialysis kynurenine and kynurenine/L − tryptophan blood ratio levels were significantly higher, when compared to the control group, indicating an increased indoleamine 2,3-dioxygenase-1 activity in hemodialysis patients. At the end of the low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers period, L − tryptophan serum levels remained unchanged vs both low−flux bicarbonate hemodialysis and hemodialfitration. Kynurenine levels instead decreased, resulting in a significant reduction of kynurenine/L − tryptophan blood ratio and indoleamine 2,3-dioxygenase-1 activity, when matched to both low−flux bicarbonate hemodialysis and HDF respectively. Serum nitric oxide control group levels, were significantly lower when compared to all hemodialysis patient groups. Interestingly, low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers nitric oxide serum levels from venous line blood samples taken 60 min after starting the hemodialysis session were significantly lower vs serum taken simultaneously from the arterial blood line.

Conclusions

The treatment with more biocompatible hemodialysis procedure as low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers, reduced indoleamine 2,3-dioxygenase-1 activity and nitric oxide formation when compared to both low−flux bicarbonate hemodialysis and hemodialfitration. These data suggest that low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers lowering hemodialysis inflammaging, could be associated to changes of proinflammatory signalling a regulated molecular level.

Trial registration

NCT Number:NCT02981992; Other Study ID Numbers: 20100014090. First submitted: November 26, 2016. First posted: December 5, 2016. Last Update Posted: December 5, 2016.
Analysis of cardiac monitoring and safety data in patients initiating fingolimod treatment in the home or in clinic
Authors: Brown Brandon , Weiss Jamie L. , Kolodny Scott , Meng Xiangyi , Williams Ian M. , Osborne John A.
Published: November 2019

Background

Fingolimod (Gilenya®) is approved for relapsing forms of multiple sclerosis in the USA. Owing to transient heart-rate effects when initiating fingolimod, eligible patients undergo precautionary baseline assessment and first-dose observation (FDO) for ≥6 h. Prior to 2014, FDO was undertaken only in clinics. As the FDO period is short, and fingolimod has accumulated evidence of a positive benefit:risk ratio, an in-home treatment-initiation program, Gilenya@Home, was developed to offer a convenient alternative.

Methods

Cardiac parameters and adverse events (AEs) were recorded by healthcare professionals performing fingolimod FDOs in the US Gilenya@Home program or in US Gilenya Assessment Network clinics. Anonymized data were collated retrospectively from the first 34 months in the home setting and from 78 months in clinics; data are reported descriptively. Satisfaction with Gilenya@Home was rated by patients using a 7-item questionnaire that considered aspects such as ease of scheduling, courtesy, and competency.

Results

Data were captured as part of standard care from 5573 patients initiating fingolimod in-home (October 2014 to July 2017) and from 15,025 patients initiating in-clinic (July 2010 to December 2016). In the Gilenya@Home questionnaire, 91.7% of 1848 respondents rated their overall satisfaction as “very good,” and 7.6% rated their satisfaction as “good.” AEs were reported for 30.7 and 32.6% of in-home and in-clinic patients, respectively. In total, 557 in-home (10.0%) and 398 in-clinic (2.6%) patients were monitored for > 6 h; 15 (0.3%) in-home and 129 (0.9%) in-clinic patients were transferred to an emergency room for overnight monitoring. The mean (standard deviation) heart rate (HR; bpm) pre-FDO was 74.8 (12.2) in-home and 74.2 (11.3) in-clinic; reduction in HR at 6 h postdose was 10.6 (12.0) and 6.3 (9.6), respectively. New-onset first-degree atrioventricular block was experienced by 132 (2.4%) in-home and 74 (0.5%) in-clinic patients, and Wenckebach (Mobitz type I) second-degree atrioventricular block by four (0.07%) and nine (0.1%) patients, with no cases of third-degree atrioventricular block.

Conclusions

A substantial number of patients have initiated fingolimod at home, reporting very high levels of satisfaction. Gilenya@Home was as rigorous as the clinic setting in detecting cardiovascular events. Overall, FDO safety outcomes were similar with Gilenya@Home and in-clinic.
Countering the poor oral health of people with intellectual and developmental disability: a scoping literature review
Authors: Wilson Nathan J. , Lin Zhen , Villarosa Amy , Lewis Peter , Philip Philcy , Sumar Bashir , George Ajesh
Published: November 2019

Background

People with intellectual and developmental disability (IDD) have poor oral health and need support to maintain optimal oral health outcomes. Little is known about how, when and where to intervene for this population. Thus the aim of this review was to summarise the existing evidence surrounding improving oral health outcomes for people with IDD.

Methods

A scoping literature review was conducted focusing on ‘oral health’ and ‘intellectual disability’. Systematic searches of five electronic databases were conducted in line with the study aims and two authors independently examined all records for relevance, with consensus achieved by a third author.

Results

A small number of approaches and interventions were identified to support people with IDD to independently maintain optimal oral hygiene. Identified studies highlighted that caregivers play a vital role in the provision of oral health support, emphasising the effectiveness of educational interventions for caregivers. However, there was uncertainty regarding the efficacy of specific tooth brushing interventions for people with IDD. In cases of more severe IDD and/or dental-related behavioural problems, dental treatment under general anaesthesia was often both a necessary and effective method of oral health care provision. The findings also identified outreach and exclusive oral health services as successful strategies for increasing the limited access of people with IDD to oral care services.

Conclusions

A uniform approach to supporting oral health for people with IDD is unlikely to succeed. A system-based approach is needed to address the diverse needs of the population of people with IDD, their caregivers and service context. Further high quality evidence is required to confirm these findings.
Psychological morbidity in Nepali cross-border migrants in India: a community based cross-sectional study
Authors: Dhungana Raja Ram , Aryal Nirmal , Adhikary Pratik , KC Radheshyam Krishna , Regmi Pramod Raj , Devkota Bikash , Sharma Guna Nidhi , Wickramage Kolitha , van Teijlingen Edwin , Simkhada Padam
Published: November 2019

Background

Since Nepali cross-border migrants can freely enter, work and stay in India, they are largely undocumented. The majority is involved in semi-skilled or unskilled jobs with limited labour rights and social security, a fact which predisposes them to psychological distress. We aimed to assess the prevalence of and factors associated with psychological morbidity among Nepali migrants upon their return from India.

Methods

A community based cross-sectional study was conducted in six districts of Nepal between September 2017 and February 2018. A total of 751 participants who had worked at least six months in India and returned to Nepal were interviewed from 24 randomly selected clusters. The General Health Questionnaire (GHQ)-12 was used to measure the psychological morbidity. Data were analysed using Poisson regression analysis.

Results

The majority was younger than 35 years (64.1%), male (96.7%), married (81.8%), had at least a primary education (66.6%), and belonged to Dalit, Janajati and religious minorities (53.7%). The prevalence of psychological morbidity was 13.5% (CI: 11.2–16.1%). Participants aged 45 years and above (adjusted prevalence ratio (aPR) = 2.74), from the Terai (aPR = 3.29), a religious minority (aPR = 3.64), who received no sick leave (aPR = 2.4), with existing health problems (aPR = 2.0) and having difficulty in accessing health care (aPR = 1.88) were more likely than others to exhibit a psychological morbidity.

Conclusion

This study demonstrated that psychological morbidity was prevalent in the study participants and varied significantly with individual characteristics, work conditions and health. Multifaceted approaches including psychological counselling for returnees and protection of labour and health rights in the workplace are recommended to help reduce psychological morbidity.
Three-dimensional finite element analysis of silk protein rod implantation after core decompression for osteonecrosis of the femoral head
Authors: Huang Liangta , Chen Feiyan , Wang Siqun , Wei Yibing , Huang Gangyong , Chen Jie , Shi Jingsheng , Naidu Rajeev K. , Xia Jun , Tao Tiger H.
Published: November 2019

Background

Several methods are available for the treatment of early-stage osteonecrosis of the femoral head. Core decompression with implantation is a widely-used treatment. However, no single implant is recognized as the most effective way to prevent disease progression. Silk has high strength and resiliency. This study explored the possibility of a strong and resilient silk protein biomaterial as a new alternative implant.

Methods

We investigated the biomechanical properties of the silk protein material by regular compression, torsion, and three-point bending tests. We established three-dimensional finite element models of different degrees of femoral head osteonecrosis following simple core decompression, fibula implantation, porous tantalum rod implantation, and silk protein rod implantation. Finally, we compared the differences in displacement and surface stress under load at the femoral head weight-bearing areas between these models.

Results

The elastic modulus and shear modulus of the silk protein material was 0.49GPa and 0.66GPa, respectively. Three-dimensional finite element analyses demonstrated less displacement and surface stress at the femoral head weight-bearing areas following silk protein rod implantation compared to simple core decompression (p < 0.05), regardless of the extent of osteonecrosis. No differences were noted in the surface deformation or surface stress of the femoral head weight-bearing areas following silk protein rod, fibula or tantalum rod implantation (p > 0.05).

Conclusions

When compared with simple core decompression, silk protein rod implantation demonstrated less displacement and surface stress at the femoral head weight-bearing area, but more than fibula or tantalum rod implantation. Similar effects on the surface stress of the femoral head between the silk rod, fibula and tantalum rod implantations, combined with additional modifiable properties support the use of silk protein as a suitable biomaterial in osteonecrosis surgery.
Coix lacryma-jobi var. ma-yuen Stapf sprout extract induces cell cycle arrest and apoptosis in human cervical carcinoma cells
Authors: Son Eun Suk , Kim Se-Hee , Kim Young Ock , Lee Young Eun , Kyung Sun Young , Jeong Sung Hwan , Kim Yu Jin , Park Jeong-Woong
Published: November 2019

Background

Cervical cancer is the second-leading cause of cancer-related mortality in females. Coix lacryma-jobi L. var. ma-yuen (Rom.Caill.) Stapf ex Hook. f. is the most widely recognized medicinal herb for its remedial effects against inflammation, endocrine system dysfunctions, warts, chapped skin, rheumatism, and neuralgia and is also a nourishing food.

Methods

To investigate the activity of Coix lacryma-jobi sprout extract (CLSE) on cell proliferation in human cervical cancer HeLa cells, we conducted a Cell Counting Kit-8 (CCK-8) assay. Flow-cytometric analysis and western blot analysis were performed to verify the effect of CLSE on the regulation of the cell cycle and apoptosis in HeLa cells.

Results

We observed that CLSE significantly inhibited cell proliferation. Furthermore, CLSE dose-dependently promoted cell cycle arrest at the sub-G1/ S phase in HeLa cells, as detected by bromodeoxyuridine (BrdU) staining. The cell-cycle-arrest effects of CLSE in HeLa cells were associated with downregulation of cyclin D1 and cyclin-dependent kinases (CDKs) 2, 4, and 6. Moreover, CLSE induced apoptosis, as determined by flow-cytometric analysis and nuclear DNA fragmentation with Annexin V/propidium iodide (PI) and 4′6′-diamidino-2-phenylindole (DAPI) staining. Induction of apoptosis by CLSE was involved in inhibition of the antiapoptotic protein B-cell lymphoma 2 (Bcl-2) and upregulation of the apoptotic proteins p53, cleaved poly (ADP-ribose) polymerase (PARP), cleaved caspase-3, and cleaved caspase-8. Finally, we observed that CLSE inactivated the phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) pathways.

Conclusions

CLSE causes cell cycle arrest and apoptotic cell death through inactivation of the PI3K/AKT pathway in HeLa cells, suggesting it is a viable therapeutic agent for cervical cancer owing to its anticancer effects.
Quality analysis of smart phone sleep apps in China: can apps be used to conveniently screen for obstructive sleep apnea at home?
Authors: Xu Zhao-feng , Luo Xin , Shi Jianbo , Lai Yinyan
Published: November 2019

Background

Obstructive sleep apnea (OSA) is a sleep disorder with a high prevalence in China. Standard diagnosis of OSA requires polysomnography (PSG). Currently, smart phone applications (apps) are widely used as an important source of health guidance. However, the quality of the information provided by these apps has not been carefully assessed.

Methods

We searched for sleep apps available in China. We designed an evaluation scale that included scientific, functionality and usability, and accountability domains. The Scientific domain included an index of 16 items to evaluate the scientific quality of the apps for their level of adherence to PSG. The functionality and usability domain included 10 items to evaluate the functions of apps and 1 item to define whether the apps needed to connect with other devices. The accountability domain included 9 items that came from the Silberg Scale to evaluate whether the information provided by apps were trustable or not. We then calculated the sum of all domains. We also evaluated the popularity of each app.

Results

A total of 2379 apps were found, and 127 met the inclusion criteria. The mean total score of the apps was 14.23 ± 3.93. The mean scores of scientific basis, functionality and usability, and accountability were 5.51 ± 2.58, 2.90 ± 1.84, and 2.90 ± 1.84. The scientific scores of apps that could connect to other devices were higher than those of apps that worked alone (mean score: 5.26 vs. 4.17, P < 0.001). The functionality and usability score was correlated with the accountability score, and the coefficient of correlation was 0.304 (P = 0.001).

Conclusions

Apps that could connect to other devices were more scientific and powerful than those that worked alone. Multifunctional apps were more popular and reliable. Because of the low quality of sleep apps in China, more work is necessary to create an ideal app.
NG2 glia regulate brain innate immunity via TGF-β2/TGFBR2 axis
Authors: Zhang Shu-zhen , Wang Qin-qin , Yang Qiao-qiao , Gu Huan-yu , Yin Yan-qing , Li Yan-dong , Hou Jin-can , Chen Rong , Sun Qing-qing , Sun Ying-feng , Hu Gang , Zhou Jia-wei
Published: November 2019

Background

Brain innate immunity is vital for maintaining normal brain functions. Immune homeostatic imbalances play pivotal roles in the pathogenesis of neurological diseases including Parkinson’s disease (PD). However, the molecular and cellular mechanisms underlying the regulation of brain innate immunity and their significance in PD pathogenesis are still largely unknown.

Methods

Cre-inducible diphtheria toxin receptor (iDTR) and diphtheria toxin-mediated cell ablation was performed to investigate the impact of neuron-glial antigen 2 (NG2) glia on the brain innate immunity. RNA sequencing analysis was carried out to identify differentially expressed genes in mouse brain with ablated NG2 glia and lipopolysaccharide (LPS) challenge. Neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice were used to evaluate neuroinflammatory response in the presence or absence of NG2 glia. The survival of dopaminergic neurons or glial cell activation was evaluated by immunohistochemistry. Co-cultures of NG2 glia and microglia were used to examine the influence of NG2 glia to microglial activation.

Results

We show that NG2 glia are required for the maintenance of immune homeostasis in the brain via transforming growth factor-β2 (TGF-β2)-TGF-β type II receptor (TGFBR2)-CX3C chemokine receptor 1 (CX3CR1) signaling, which suppresses the activation of microglia. We demonstrate that mice with ablated NG2 glia display a profound downregulation of the expression of microglia-specific signature genes and remarkable inflammatory response in the brain following exposure to endotoxin lipopolysaccharides. Gain- or loss-of-function studies show that NG2 glia-derived TGF-β2 and its receptor TGFBR2 in microglia are key regulators of the CX3CR1-modulated immune response. Furthermore, deficiency of NG2 glia contributes to neuroinflammation and nigral dopaminergic neuron loss in MPTP-induced mouse PD model.

Conclusions

These findings suggest that NG2 glia play a critical role in modulation of neuroinflammation and provide a compelling rationale for the development of new therapeutics for neurological disorders.
Characteristics of atheromatosis in the prediabetes stage: a cross-sectional investigation of the ILERVAS project
Authors: Sánchez Enric , Betriu Àngels , López-Cano Carolina , Hernández Marta , Fernández Elvira , Purroy Francisco , Bermúdez-López Marcelino , Farràs-Sallés Cristina , Barril Silvia , Pamplona Reinald , Rius Ferran , Hernández Cristina , Simó Rafael , Lecube Albert ,   the ILERVAS project collaborators, Barbé Ferran , Valdivielso José-Manuel , Arqué Glòria , González Jessica , Vena Ana , Miquel Eva , Ortega-Bravo Marta , Torres Gerard , Cambray Serafín , Portero-Otin Manuel , Jové Mariona , Martínez-Alonso Montserrat , Castro Eva , Godoy Pere
Published: November 2019

Background

Prediabetes has recently been associated with subclinical atheromatous disease in the middle-aged population. Our aim was to characterize atheromatous plaque burden by the number of affected territories and the total plaque area in the prediabetes stage.

Methods

Atheromatous plaque burden (quantity of plaques and total plaque area) was assessed in 12 territories from the carotid and femoral regions using ultrasonography in 6688 non-diabetic middle-aged subjects without cardiovascular disease. Prediabetes was defined by glycosylated hemoglobin (HbA1c) between 5.7 and 6.4% according to the American Diabetes Association guidelines.

Results

Prediabetes was diagnosed in 33.9% (n = 2269) of the ILERVAS participants. Subjects with prediabetes presented a higher prevalence of subclinical atheromatous disease than participants with HbA1c < 5.7% (70.4 vs. 67.5%, p = 0.017). In the population with prediabetes this was observed at the level of the carotid territory (p < 0.001), but not in the femoral arteries. Participants in the prediabetes stage also presented a significantly higher number of affected territories (2 [1;3] vs. 1 [0;3], p = 0.002), with a positive correlation between HbA1c levels and the number of affected territories (r = 0.068, p < 0.001). However, atheromatosis was only significantly (p = 0.016) magnified by prediabetes in those subjects with 3 or more cardiovascular risk factors. The multivariable logistic regression model showed that the well-established cardiovascular risk factors together with HbA1c were independently associated with the presence of atheromatous disease in participants with prediabetes. When males and females were analyzed separately, we found that only men with prediabetes presented both carotid and femoral atherosclerosis, as well as an increase of total plaque area in comparison with non-prediabetic subjects.

Conclusions

The prediabetes stage is accompanied by an increased subclinical atheromatous disease only in the presence of other cardiovascular risk factors. Prediabetes modulates the atherogenic effect of cardiovascular risk factors in terms of distribution and total plaque area in a sex-dependent manner.

Trial registration NCT03228459 (clinicaltrials.gov)
Explaining income-related inequalities in cardiovascular risk factors in Tunisian adults during the last decade: comparison of sensitivity analysis of logistic regression and Wagstaff decomposition analysis
Authors: Saidi Olfa , Zoghlami Nada , Bennett Kathleen E. , Mosquera Paola Andrea , Malouche Dhafer , Capewell Simon , Romdhane Habiba Ben , O’Flaherty Martin
Published: November 2019

Background

It is important to quantify inequality, explain the contribution of underlying social determinants and to provide evidence to guide health policy. The aim of the study is to explain the income-related inequalities in cardiovascular risk factors in the last decade among Tunisian adults aged between 35 and 70 years old.

Methods

We performed the analysis by applying two approaches and compared the results provided by the two methods. The methods were global sensitivity analysis (GSA) using logistic regression models and the Wagstaff decomposition analysis.

Results

Results provided by the two methods found a higher risk of cardiovascular diseases and diabetes in those with high socio-economic status in 2005. Similar results were observed in 2016.

In 2016, the GSA showed that education level occupied the first place on the explanatory list of factors explaining 36.1% of the adult social inequality in high cardiovascular risk, followed by the area of residence (26.2%) and income (15.1%). Based on the Wagstaff decomposition analysis, the area of residence occupied the first place and explained 40.3% followed by income and education level explaining 19.2 and 14.0% respectively. Thus, both methods found similar factors explaining inequalities (income, educational level and regional conditions) but with different rankings of importance.

Conclusions

The present study showed substantial income-related inequalities in cardiovascular risk factors and diabetes in Tunisia and provided explanations for this. Results based on two different methods similarly showed that structural disparities on income, educational level and regional conditions should be addressed in order to reduce inequalities.
Triglyceride to high-density lipoprotein cholesterol ratio is associated with increased mortality in older patients on peritoneal dialysis
Authors: Zhan Xiaojiang , Yang Mei , Zhou Ruitong , Wei Xin , Chen Yanbing , Chen Qinkai
Published: November 2019

Background

The triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) has been suggested as a simple method to identify unfavorable cardiovascular (CV) outcomes in the general population. The aim of this study was to investigate the association between the TG/HDL-C ratio and all-cause and CV mortality in peritoneal dialysis (PD) patients.

Methods

We retrospectively analyzed patients on PD from November 1, 2005, to February 28, 2017, with a follow-up period lasting until May 31, 2017. The main outcomes were all-cause and CV mortality.

Results

Among the 973 PD patients, the mean age was 49.67 ± 14.58 (y). During a median follow-up period of 27.2 months (IQR = 13.4–41.5 months), 229 (23.5%) patients died, with 120 (12.3%) dying as a result of CV diseases. The median serum TG/HDL-C ratio was 1.11 (IQR = 0.71–1.80). In a multivariate Cox regression analysis, patients with higher TG/HDL-C ratio levels (tertile 3) had a higher incidence of CV mortality (adjusted HR = 2.12; 95% CI: 1.21–3.72; P = 0.009) and all-cause mortality (adjusted HR = 2.08; 95% CI: 1.37–3.14; P = 0.001) compared to patients in tertile 1. These associations persisted after excluding the patients who have already taken lipid-lowering medications. For older patients (> 60 years), each 1-unit higher baseline TG/HDL-C level was associated with a 48% (95% CI: 1.06–2.07; P = 0.021) increased risk of all-cause mortality and a 59% (95% CI: 1.03–2.45; P = 0.038) increased risk of CV mortality; however, this association was not observed in patients ≤60 years of age.

Conclusions

A higher serum TG/HDL-C ratio was an independent predictor of all-cause and CV mortality in PD patients. Furthermore, an elevated TG/HDL-C ratio was significantly associated with higher all-cause and CV mortality in older PD patients.
Myocardial tissue characterisation using echocardiographic deformation imaging
Authors: Moharram Mohammed A. , Lamberts Regis R. , Whalley Gillian , Williams Michael J. A. , Coffey Sean
Published: November 2019

Myocardial pathology results in significant morbidity and mortality, whether due to primary cardiomyopathic processes or secondary to other conditions such as ischemic heart disease. Cardiac imaging techniques characterise the underlying tissue directly, by assessing a signal from the tissue itself, or indirectly, by inferring tissue characteristics from global or regional function. Cardiac magnetic resonance imaging is currently the most investigated imaging modality for tissue characterisation, but, due to its accessibility, advanced echocardiography represents an attractive alternative. Speckle tracking echocardiography (STE) is a reproducible technique used to assess myocardial deformation at both segmental and global levels. Since distinct myocardial pathologies affect deformation differently, information about the underlying tissue can be inferred by STE. In this review, the current available studies correlating STE deformation parameters with underlying tissue characteristics in humans are examined, with separate emphasis on global and segmental analysis. The current knowledge is placed in the context of integrated backscatter and the future of echocardiographic based tissue characterisation is discussed. The use of these imaging techniques to more precisely phenotype myocardial pathology more precisely will allow the design of translational cardiac research studies and, potentially, tailored management strategies.
Idelalisib addition has neutral to beneficial effects on quality of life in bendamustine/rituximab-treated patients: results of a phase 3, randomized, controlled trial
Authors: Montillo Marco , Illés Árpád , Robak Tadeusz , Pristupa Alexander S. , Wach Malgorzata , Egyed Miklós , Delgado Julio , Jurczak Wojciech , Morschhauser Franck , Schuh Anna , Eradat Herbert , Shreay Sanatan , Barrientos Jacqueline C. , Zelenetz Andrew D.
Published: November 2019

Background

In a phase 3 randomized, double-blind, placebo-controlled trial, treatment with idelalisib, a phosphoinositol-3 kinase δ inhibitor, + bendamustine/rituximab improved progression-free survival (PFS) and overall survival (OS) in adult patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL). Here we report the results of health-related quality of life (HRQL) analyses from this study.

Methods

From June 15, 2012 to August 21, 2014, 416 patients with R/R CLL were enrolled; 207 patients were randomized to the idelalisib arm and 209 to the placebo arm. In the 416 patients randomized to receive bendamustine/rituximab and either oral idelalisib 150 mg twice-daily or placebo, HRQL was assessed at baseline and throughout the blinded part of the study using the Functional Assessment of Cancer Therapy–Leukemia (FACT-Leu) and EuroQoL Five-Dimension (EQ-5D) visual analogue scale (VAS) questionnaires. The assessments were performed at scheduled patient visits; every 4 weeks for the first 6 months from the initiation of treatment, then every 8 weeks for the next 6 months, and every 12 weeks thereafter until end of study. Least-squares mean changes from baseline were estimated using a mixed-effects model by including treatment, time, and treatment-by-time interaction, and stratification factors as fixed effects. Time to first symptom improvement was assessed by Kaplan-Meier analysis.

Results

In mixed-effects model analysis, idelalisib + bendamustine/rituximab treatment led to clinically meaningful improvements from baseline in leukemia-associated symptoms. Moreover, per Kaplan-Meier analysis, the proportion of patients with symptom improvement was higher and time to improvement was shorter among patients in the idelalisib-containing arm compared with those who did not receive idelalisib. The physical and social/family FACT-Leu subscale scores, along with the self-rated health assessed by EQ-VAS, showed improvement with idelalisib over placebo, but the difference did not reach statistical significance. The functional and emotional FACT-Leu subscale scores remained similar to placebo.

Conclusions

Addition of idelalisib to bendamustine/rituximab, apart from improving PFS and OS, had a neutral to beneficial impact on HRQL in patients with R/R CLL, particularly by reducing leukemia-specific disease symptoms.

Trial registration

Clinicaltrials.gov NCT01569295. Registered April 3, 2012.
Psychological wellbeing in a resource-limited work environment: examining levels and determinants among health workers in rural Malawi
Authors: Lohmann Julia , Shulenbayev Olzhas , Wilhelm Danielle , Muula Adamson S. , De Allegri Manuela
Published: November 2019

Background

A competent, responsive, and productive health workforce is central to a well-performing health system capable of providing universal access to high-quality care. Ensuring health workers’ psychological wellbeing is critical to sustaining their availability and productivity. This is particularly true in heavily constrained health systems in low- and lower-middle-income countries. Research on the issue, however, is scarce. This study aimed to contribute to filling the gap in knowledge by investigating levels of and factors associated with psychological wellbeing of mid-level health workers in Malawi.

Methods

The study relied on a cross-sectional sample of 174 health workers from 33 primary- and secondary-level health facilities in four districts of Malawi. Psychological wellbeing was measured using the WHO-5 Wellbeing Index. Data were analyzed using linear and logistic regression models.

Results

Twenty-five percent of respondents had WHO-5 scores indicative of poor psychological wellbeing. Analyses of factors related to psychological wellbeing showed no association with sex, cadre, having dependents, supervision, perceived coworker support, satisfaction with the physical work environment, satisfaction with remuneration, and motivation; a positive association with respondents’ satisfaction with interpersonal relationships at work; and a negative association with having received professional training recently. Results were inconclusive in regard to personal relationship status, seniority and responsibility at the health facility, clinical knowledge, perceived competence, perceived supervisor support, satisfaction with job demands, health facility level, data collection year, and exposure to performance-based financing.

Conclusions

The high proportion of health workers with poor wellbeing scores is concerning in light of the general health workforce shortage in Malawi and strong links between wellbeing and work performance. While more research is needed to draw conclusions and provide recommendations as to how to enhance wellbeing, our results underline the importance of considering this as a key concern for human resources for health.
Atheroprotective effects of methotrexate via the inhibition of YAP/TAZ under disturbed flow
Authors: Liu Dandan , Lv Hang , Liu Qi , Sun Yanli , Hou Shenglong , Zhang Lu , Yang Mengyue , Han Baihe , wang Gang , Wang Xuedong , Du Wenjuan , Nie Honggang , Zhang Ruoxi , Huang Xingtao , Hou Jingbo , Yu Bo
Published: November 2019

Background

Atherosclerosis preferentially develops in regions of disturbed flow (DF). Emerging evidence indicates that yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), which are both effectors of the Hippo pathway, sense different blood flow patterns and regulate atherosclerotic lesions. We previously found that methotrexate (MTX) reduces in-stent neoatherosclerosis, decreases the plaque burden, and has an effect on local fluid shear stress. Here, we investigated the atheroprotective effect of MTX under DF and the mechanisms underlying these properties.

Methods

Human umbilical vein endothelial cells (HUVECs) were subjected to biomechanical stretch using a parallel-plate flow system and treated with or without MTX at therapeutically relevant concentrations. Additionally, an extravascular device was used to induce DF in the left common carotid artery of C57BL/6 mice, followed by treatment with MTX or 0.9% saline. The artery was then assessed histopathologically after 4 weeks on a Western diet.

Results

We observed that MTX significantly inhibited DF-induced endothelial YAP/TAZ activation. Furthermore, it markedly decreased pro-inflammatory factor secretion and monocyte adhesion in HUVECs but had no effect on apoptosis. Mechanistically, AMPKa1 depletion attenuated these effects of MTX. Accordingly, MTX decreased DF-induced plaque formation, which was accompanied by YAP/TAZ downregulation in vivo.

Conclusions

Taken together, we conclude that MTX exerts protective effects via the AMP-dependent kinase (AMPK)-YAP/TAZ pathway. These results provide a basis for the prevention and treatment of atherosclerosis via the inhibition of YAP/TAZ.
Profiling the microRNA signature of the peripheral sensory ganglia in experimental autoimmune encephalomyelitis (EAE)
Authors: Friedman Timothy N. , Yousuf Muhammad Saad , Catuneanu Ana , Desai Mansi , Juźwik Camille A. , Fournier Alyson E. , Kerr Bradley J.
Published: November 2019

Background

Multiple sclerosis is an autoimmune disease with a distinct female bias, as well as a high prevalence of neuropathic pain in both sexes. The dorsal root ganglia (DRG) contain the primary sensory neurons that give rise to pain, and damage to these neurons may lead to neuropathic pain. Here, we investigate the sex differences of the DRG transcriptome in a mouse model of MS.

Methods

Next-generation sequencing was used to establish RNA and microRNA profiles from the DRG of mice with MOG35–55-induced EAE, a model of CNS inflammation that mimics aspects of MS. Differential expression and multiple meta-analytic approaches were used to compare expression profiles in immunized female and male mice. Differential expression of relevant genes and microRNAs were confirmed by qPCR.

Results

Three thousand five hundred twenty genes and 29 microRNAs were differentially expressed in the DRG of female mice with MOG35–55-EAE, while only 189 genes and 3 microRNAs were differentially expressed in males with MOG35–55-EAE. Genes related to the immune system were uniquely regulated in immunized female mice. Direct comparison of sex within disease indicates significant differences in interferon and phagosomal pathways between the sexes. miR-21a-5p is the primary dysregulated microRNA in both sexes, with females having additional dysregulated microRNAs, including miR-122-5p.

Conclusions

This study provides evidence that females are uniquely affected by MOG35–55-EAE and that this difference may result from additional signaling not present in the male. The altered transcriptome of females correlates with other studies finding hyperactivity of pain-sensing neurons and suggests underlying sex-specific pathways for neuropathic pain.
Anti-neuroinflammation ameliorates systemic inflammation-induced mitochondrial DNA impairment in the nucleus of the solitary tract and cardiovascular reflex dysfunction
Authors: Fu Mu-Hui , Chen I-Chun , Lee Chou-Hwei , Wu Chih-Wei , Lee Yu-Chi , Kung Yu Chih , Hung Chun-Ying , Wu Kay L. H.
Published: November 2019

Background

Decreased heart rate variability (HRV) leads to cardiovascular diseases and increased mortality in clinical studies. However, the underlying mechanisms are still inconclusive. Systemic inflammation-induced neuroinflammation is known to impair the autonomic center of cardiovascular regulation. The dynamic stability of blood pressure and heart rate (HR) is regulated by modulation of the reciprocal responses of sympathetic and parasympathetic tone by the baroreflex, which is controlled by the nucleus of the solitary tract (NTS).

Methods

Systemic inflammation was induced byE. colilipopolysaccharide (LPS, 1.2 mg/kg/day, 7 days) peritoneal infusion via an osmotic minipump in normotensive Sprague-Dawley rats. Systolic blood pressure (SBP) and HR were measured by femoral artery cannulation and recorded on a polygraph under anesthesia. The low-frequency (LF; 0.25–0.8 Hz) and high-frequency (HF; 0.8–2.4 Hz) components of SBP were adopted as the indices for sympathetic vasomotor tone and parasympathetic vasomotor tone, while the baroreflex effectiveness index (BEI) was adopted from the analysis of SBP and pulse interval (PI). The plasma levels of proinflammatory cytokines and mitochondrial DNA (mtDNA) oxidative damage were analyzed by ELISA. Protein expression was evaluated by Western blot. The distribution of oxidative mtDNA was probed by immunofluorescence. Pharmacological agents were delivered via infusion into the cisterna magna with an osmotic minipump.

Results

The suppression of baroreflex sensitivity was concurrent with increased SBP and decreased HR. Neuroinflammatory factors, including TNF-α, CD11b, and Iba-1, were detected in the NTS of the LPS group. Moreover, indices of mtDNA damage, including 8-OHdG and γ-H2AX, were significantly increased in neuronal mitochondria. Pentoxifylline or minocycline intracisternal (IC) infusion effectively prevented mtDNA damage, suggesting that cytokine and microglial activation contributed to mtDNA damage. Synchronically, baroreflex sensitivity was effectively protected, and the elevated blood pressure was significantly relieved. In addition, the mtDNA repair mechanism was significantly enhanced by pentoxifylline or minocycline.

Conclusion

These results suggest that neuronal mtDNA damage in the NTS induced by neuroinflammation could be the core factor in deteriorating baroreflex desensitization and subsequent cardiovascular dysfunction. Therefore, the enhancement of base excision repair (BER) signaling in mitochondria could be a potential therapeutic strategy for cardiovascular reflex dysregulation.
Impact of internal female migration on unmet need for modern contraception in Zambia
Authors: Almonte Melanie T. , Lynch Caroline A.
Published: November 2019

Background

Unmet need for contraception, the proportion of women who want to limit or delay childbirth but use no form of contraception, is the core indicator to evaluate the effectiveness of family planning programs. Understanding how migration influences unmet need is important to identify to whom and how to target sexual and reproductive health programs. We assessed how migration status in rural and urban settings is associated with having an unmet need for family planning.

Methods

Data on sexually active, fecund, reproductive-aged (15–49 years) women from the 2013–14 Zambia Demographic and Health Survey were analysed through univariate and multivariate logistic regression models.

Results

Unmet need for modern contraceptive methods was significantly higher among rural to rural migrant women (OR 1.30, 95%CI 1.00–1.70p < 0.05) and rural non-migrant women (OR 1.41, 95%CI 1.06–1.85p < 0.01) compared to urban non-migrant women after controlling for age, marital status, parity, religion, education and wealth.

Conclusion

Women residing in, and migrating between, rural areas were significantly more likely to have an unmet need for contraception. Our findings highlight the importance of understanding migration and migrant streams to strengthen family planning programs. In Zambia, a focus on rural-rural migrants, rural non-migrants and the poorest could improve the health of the entire population.
Randomized controlled trial protocol to evaluate the effect of an educational intervention using information, motivation and behavioral skills model on sexual satisfaction of new couples in Iran
Authors: Moeini Babak , Merghati Khoei Effat , Barati Majid , Soltanian Alireza , Sharma Manoj , Khadivi Reza , Ghaleiha Ali , Nahar Vinayak K. , Bagherikholenjani Fahimeh
Published: November 2019

Background

Sexual satisfaction is considered as one of the key factors in assessing a person’s quality of life and the quality and continuity of marital relationships. According to the results of reports in Iran, many couples are dissatisfied with their sexual lives. Sexuality education is one of the important strategies to prevent early sexual problems and improve sexual satisfaction. The aim of this randomized controlled trial is to compare the efficacy of sexual and marital enrichment package using information, motivation and behavioral skills model on sexual satisfaction of new couples in Iran to routine sexual care program that provided at governmental health centers.

Methods

This is a randomized, controlled, superiority trial with two parallel groups. One hundred new couples (n = 200) will be recruited and randomized with simple randomization method and a 1:1 allocation. Recruitment will be from governmental health centers and calling on social networks. Couples will be randomized to intervention which will receive Sexual and Marital Enrichment package and control group (routine care at health centers). Couples will be followed up for 4 months. Then primary outcomes (mean score of couples’ sexual information, motivation and behavior skills) and secondary outcome (mean score of couples’ sexual satisfaction) of study will be measured through the online questionnaire.

Discussion

This trial will be examined the impact of the sexual and marital skills training package tailored to the values and norms governing the sexual life of Iranian couples on their sexual satisfaction. If the trial is effective, its results will be presented to policy makers for implementation at national level.

Trial registration

(Iranian Registry of Clinical Trials (IRCT) number): IRCT20181211041926N1. Date of registration: March 2, 2019.