bluuebunny/crossref_metadata_2025 huggingface dataset:
Burnout Syndrome, Extracurricular Activities and Social Support Among Brazilian Internship Medical Students: a Cross-Sectional Analysis.
Authors: Fontana Maria Carolina Pedro , Generoso Igor Prado , Sizilio Alexandre , Bivanco-Lima Danielle
Published: February 2020

Background: Burnout syndrome (BS) is highly prevalent among medical students and is associated with lower empathy and worsening of medical students ́ mental health. The aim of our study was to identify prevalence of BS during internship and its association with self-related social support and participation in extracurricular activities in one medical school in Brazil. Methods: This was a cross-sectional study conducted in 2015, with 121 medical students on internship (56% response rate). They were evaluated using the Maslach Burnout Inventory – Human Services (MBI) and assessed about socio demographic data, social support and extracurricular activities. Results: The overall BS prevalence was 57.5% among medical interns. High emotional exhaustion was present in 33.1% (N=38) of interns, high depersonalization was observed in 45.7% (N=58) and 36.2% of participants (N=46) had low personal accomplishment. Individuals with participation in community services had lower frequency of depersonalization (PR 0.61 CI95% 0.42-0.88). BS was not associated with different types of extracurricular activities and no association was found among BS and the behaviour of seeking social support. Conclusions: We found high prevalence of BS in medical interns, however the behaviour of seeking social support had no association with BS. The interns participating in community activities had lower frequency of high depersonalization.
Essential Newborn Care Utilization and Associated Factors in Ethiopia: A Systematic Review and Meta-Analysis
Authors: Alamneh Yoseph Merkeb , Adane Fentahun , Yirga Tadesse , Desta Melaku
Published: February 2020

Background: Globally, newborn death accounted for 46% of under-five deaths and more than 80% of newborn deaths are the result of preventable and treatable conditions. Reports on the prevalence and associated factors of essential newborn care utilization are highly variable and inconsistent across Ethiopia. Therefore, this systematic review and meta-analysis aimed to estimate the pooled prevalence of essential newborn care utilization and associated factors in Ethiopia.
Methods : The international databases include: MEDLINE/PubMed, EMBASE, Web of Sciences, Scopus, Google Scholar, Science Direct, Cochrane library and others were scientifically explored. We considered all primary studies reporting the prevalence of essential newborn care utilization and associated factors in Ethiopia. We retrieved all necessary data by using a standardized data extraction format spreadsheet. STATA 14 statistical software was used to analyze the data and Cochrane Q test statistics and I 2 test was used to assess the heterogeneity between the studies.Random effect model was employed.
Results: The pooled estimate of essential newborn care utilization from 11 studies in Ethiopia was 48.768% (95% CI: 27.891, 69.645). Residence [ OR = 2.50 (95% CI: 1.64, 3.88)], Postnatal care [OR=5.53, 95% CI = (3.02, 10.13], counseling during pregnancy and delivery [OR=4.39, 95% CI = (2.99, 6.45], antenatal care follows up (OR=6.84; 95% CI: 1.15, 4.70) and maternal educational status [OR = 1.63 (95% CI: 1.12, 2.37)] were identified as the associated factors of essential newborn care utilization.
Conclusion: Based on the current study essential newborn care utilization in Ethiopia was significantly low as compared to the current global recommendation on essential newborn care utilization. Place of residence, Postnatal care, counseling during pregnancy and delivery, antenatal care follows up and maternal educational status were associated risk factors variables. Therefore, on the basis of the results, it is suggested that special attention should be given to attempts to ensure that education should focus on women during ante and postnatal follow-up, counseling during pregnancy and delivery, as well as rural and illiterate mothers. Finally, appropriate newborn services utilization at health facilities and raising mother’s level of awareness about newborn care practices should be recommended.
Incidence and time trends of sarcoma (2000-2013): results from the French Network of Cancer registries (FRANCIM)
Authors: amadeo brice , Penel Nicolas , Coindre Jean-Michel , Ray-coquard Isabelle , Ligier Karine , Delafosse Patricia , Bouvier Anne-Marie , Plouvier Sandrine , Gallet Justine , Lacourt Aude , Coureau Gaëlle , Mathoulin-Pélissier Simone , Desandes Emmanuel
Published: February 2020

Background : The exhaustive collection of new sarcoma cases and their second histologic review offer a unique opportunity to study their incidence and time trends in France according to the major subtypes. Methods : Data were collected from population-based cancer registries covering 22% of the French population. Crude and world age-standardized incidence rates (ASR) were estimated according to anatomic, histological and genetic groups, age and sex over the 2010-2013 period.
Results: Time trends in incidence were calculated by the annual percent change over the 2000-2013 period. During the most recent period (2010-2013), 3,942 patients with sarcoma were included. The ASR of soft-tissue and bone sarcomas, and gastro-intestinal stromal tumors (GIST) were 2.1, 1.0 and 0.6, respectively. For the four most frequent histological subtypes (unclassified, leiomyosarcoma, GIST and liposarcoma), the ASR ranged from 0.4 to 0.7. ASRs were 1.9 for complex genomic and 1.3 for recurrent translocation sarcomas. The time-trend analysis showed a significant increase of sarcoma incidence rate between 2000 and 2005, which stabilized thereafter. Incidence rates increased for four histological subtypes (GIST, chondrosarcoma, myxofibrosarcoma, solitary fibrous tumors) and decreased for three (leiomyosarcomas, Kaposi sarcoma and fibrosarcoma).
Conclusion : To our knowledge, this study is the first to investigate sarcoma incidence based on a systematic pathological review of these cancers and on the updated sarcoma classifications. Due to the paucity of literature on sarcomas, future studies using data from population-based cancer registries should consider a standardized inclusion criterion presented in our study to better describe and compare data between countries.
The association between climate, geography and respiratory syncitial virus hospitalizations among children in Ontario, Canada: a population-based study
Authors: Radhakrishnan Dhenuka , Ouedraogo Alexandra , Shariff Salimah Z. , McNally Dayre , Benchimol Eric I. , Clemens Kristin K.
Published: February 2020

Background: Respiratory syncytial virus (RSV) infection is a major cause of hospitalization in young children in Canada, despite routine immunoprophylaxis in those with medical risk factors. We aimed to determine if cold temperatures are associated with RSV hospitalization. Methods: We conducted a population-based nested case–control study of children in Ontario, Canada, using health administrative data. We compared children hospitalized for RSV between September 1, 2011 and August 31, 2012 to age and sex matched controls. We used multivariable logistic regression to identify associations between minimum daily temperature and RSV hospitalizations with adjustment for sociodemographic and environmental factors. Results: We identified 1670 children with RSV hospitalizations during the study period and 6680 matched controls. Warmer temperatures (OR=0.94, 95%CI: 0.93, 0.95) were associated with lower odds of RSV hospitalization. Southern ecozone (OR=1.6, 95%CI: 1.2, 2.1), increased ozone concentration (OR=1.03, 95%CI: 1.01, 1.06) and living in a lower income neighbourhood (OR=1.3, 95%CI: 1.1, 1.5) significantly increased the odds of RSV hospitalization, as did living in a household with a larger number of siblings in a sub-cohort of children (OR=1.34, 95%CI: 1.26, 1.41). Conclusions: In Ontario, the likelihood of having an RSV hospitalization is associated with colder temperature exposures and socioeconomic factors.
Symptoms in the general Norwegian adult population - prevalence and associated factors
Authors: Krogstad Hilde , Loge Jon Håvard , Grotmol Kjersti , Kaasa Stein , Kiserud Cecilie Essholt , Salvesen Øyvind , Hjermstad Marianne Jensen
Published: February 2020

Background

Patients´ own perceptions and evaluations of symptoms, functioning and other health-related factors, i.e. Patient Reported Outcomes (PROs), are important elements for providing good patient care. Symptoms are subjective and best elicited by the patient orally or by using PRO measures (PROMs). Reference values on frequently used PROMs facilitate the interpretation of PROMs scores both in clinics and research settings, by comparing patient data with relevant samples from the general population.

Objectives

Study objectives were to (1) present reference values for the M.D. Anderson Symptom inventory (MDASI) (2) examine the occurrence and intensity of symptoms assessed by the MDASI in a general Norwegian adult population sample, and (3) examine factors associated with higher symptom burden defined as the sum score of all symptoms, and factors associated with symptoms` interference on functions

Methods

In 2015, MDASI was sent by mail to a representative sample of the general Norwegian adult population (N = 6165). Medical comorbidities were assessed by the Self-Administered Comorbidity Questionnaire. Depression was self-reported on the Patient Health Questionnaire 9 (PHQ-9). Linear multivariable regression analysis was used to examine for factors associated with MDASI sum score and factors associated with symptoms’ interference on functions.

Results

The response rate was 36%. More females (54%) than males (46%) responded. Mean age was 55 years (SD 14). The most frequent symptoms were fatigue (59.7%), drowsiness (56.2%) and pain (56.1%). Fatigue, pain and disturbed sleep had the highest mean scores. The presence of one or more comorbidities, increasing PHQ-9 score and lower level of education were associated with higher MDASI sum score (p<0.001). The MDASI sum score and the PHQ-9 score were positively associated with all interference items (p<0.001) except for walking (p=0.22).

Conclusion

This study provides the first Norwegian reference values for the MDASI. The presence of one or more comorbidities, higher level of depressive symptoms and lower level of education were significantly associated with higher MDASI sum score. These covariates must be controlled for when using the reference values.
High expression of CD52 predicts poor prognosis of cytogenetic normal acute myeloid leukemia
Authors: Cai Ping , Cai Wenzhi , Xu Xiaoyu , Yang xiaofei , Wang yemin , Wu Depei , Chen Suning
Published: February 2020

Background: The prognosis of cytogenetic normal acute myeloid leukemia (CN-AML) varies. Finding new biomarkers affecting the prognosis of these patients may bring a new strategy for precise classification and treatment. CD52 play a significant role in chronic lymphocytic leukemia (CLL). However, the potential role of CD52 in CN-AML remains largely elusive. Methods: We analyzed the prognostic role of different expression levels of CD52 in 58 CN-AML from The Cancer Genome Atlas (TCGA) dataset and validate these results with 345 CN-AML patients from Gene Expression Omnibus (GEO) dataset. Results: CN-AML patients with high CD52 mRNA expression have a poorer prognosis compared to low CD52 expression ( event-free survival [EFS], P =0.056; overall survival [OS], P=0.043; log-rank test) and the results was verified by GSE12417 (OS, P=0.0197; log-rank test) and GSE71014 (OS, P=0.0197; log-rank test). Hematopoietic stem cell transplantation (HSCT) may improve prognosis of patients with CD52 high . Multivariate cox regression analysis show that the expression level of CD52 (HR=1.503; 95%CI:1.158-1.949 ; P=0.002) was a prognostic factor independent of age (HR=3.045; 95%CI:1.524-6.086; P=0.002) and FLT3 mutation status (HR=2.219; 95%CI:1.123-4.382; P=0.022). CD52 gene expression show a predictive effect on EFS (1-year survival- area under the curve [AUC]:0.685, 2-year survival-AUC:0.752) and OS (1-year survival-AUC: 0.717, 2-year survival-AUC:0.770). Besides, we also found that there is a significant negative correlation between CD52 mRNA expression and DNA methylation . CD52 DNA demethylation may responsible for the high level of CD52 mRNA. Functional enrichment analysis of differentially expressed genes in CD52 high and CD52 low suggests that leukemia cell adhesion-related pathways may be associated with poor prognosis in CD52 high patients . Conclusions: CD52 gene mRNA overexpression is an independent adverse prognostic factor for CN-AML, which could be reversed by HSCT. CD52 DNA demethylation may responsible for the high level of CD52 mRNA. The poor prognosis of patients with CD52 high may involves in leukemia cell adhesion-related pathways. Whether CD52 monoclonal antibodies play a role in high risk patients need further research.
Good Clinical Middle-term Outcomes of the Reduction of Posterior Cruciate Ligament Avulsion Fracture in Cruciate Retaining Total Knee Arthroplasty
Authors: Lin Wei , Niu Jinghui , Dai Yike , Zhang Huaxing , Zhu Jing , Wang Fei
Published: February 2020

Background Intraoperative posterior cruciate ligament (PCL) avulsion fracture of tibial is an uncommon but serious complication during primary cruciate retaining (CR) total knee arthroplasty (TKA). However, the clinical outcomes and patient-reported outcome (PRO) of the reduction of PCL avulsion fracture of tibial have rarely been informed. The objective of this research was to investigate the prevalence and middle-term clinical outcomes of this kind of fracture during primary CR TKA and to identify the potential risk factors. Methods A retrospective cohort study from January 2014 to January 2016, 56 patients who experienced PCL avulsion fracture of tibial and intraoperative reduction during primary CR TKA as PCL avulsion group, matched in a 4:1 ratio of 224 patients who underwent primary CR TKA as control group for comparison. All patients were followed up at least 4 years. Patients’ demographics, before surgery and last follow-up after surgery including range of motion (ROM), Knee Society Score (KSS), Forgotten joint score (FJS) were assessed in the two groups, Logistic regression to identify the potential risk factors. Results In our series of 1216 patients who underwent CR TKA during the retrospective period, 56 patients (4.6%) experienced PCL avulsion fracture of tibial. There were no noteworthy differences in demographic, ROM, KSS, FJS scores of the patients between the two groups. In PCL avulsion fracture group, no patients experienced revision due to the knee instability. Logistic regression analysis showed that older age (P = 0.032) and female gender (P = 0.041) were the risk factors of PCL avulsion fracture of tibial. Conclusions The incidence of PCL avulsion fracture of tibial is 4.6%, older patients and female gender may be the two risk factors of PCL avulsion fracture. The reduction of PCL avulsion fracture during CR TKA can achieve an excellent middle-term clinical and PRO outcomes compared with the control group, and without increased the risk of complications.
Prevalence and significance of potential drug-drug interactions among cancer patients receiving chemotherapy
Authors: Ismail Mohammad , Khan Sehrash , Khan Fahadullah , Noor Sidra , Sajid Hira , Yar Shazia , Rasheed Irum
Published: February 2020

Background: Cancer patients often receive multiple drugs to maximize their therapeutic benefit, treat co-morbidities and counter the adverse effects of chemotherapy. Concomitant administration of multiple drugs increases the risk of drug interactions leading to compromised therapeutic efficacy or safety of therapy. The purpose of this study was to identify the prevalence, levels and predictors of potential drug-drug interactions (pDDIs) among cancer patients.
Methods: Six hundred and seventy-eight patients receiving chemotherapy from two tertiary care hospitals were included in this study. Patient medication profiles were screened for pDDIs using the Micromedex® database. Logistic regression analysis was performed to identify the predictors of pDDIs.
Results: The overall prevalence of pDDIs was 78%, majority of patients had 1-2 pDDIs (39.2%). A total of 1843 pDDIs were detected. Major-pDDIs were most frequent (67.3%) whereas, a significant association of pDDIs was found between >7 all prescribed drugs (p <0.001) and ≥3 anti-cancer drugs (p <0.001). Potential adverse outcomes of these interactions include reduced therapeutic effectiveness, QT interval prolongation, tendon rupture, bone marrow suppression and neurotoxicity.
Conclusions: Major finding of this study is the high prevalence of pDDIs signifying the need of strict patient monitoring for pDDIs among cancer patients. Patients at higher risk to pDDIs include those prescribed with >7 any types of drugs or ≥3 anticancer drugs. Moreover, list of most frequently identified major and moderate interactions will aid health care professional in timely identification and prevention of pDDIs.
Level of Adult Client Satisfaction with Clinic Flow Time and Services of an Integrated Non-Communicable Disease-HIV Testing Services Clinic in Soweto, South Africa: A Cross-Sectional Study
Authors: Hopkins Kathryn Lee , Hlongwane Khuthadzo E , Otwombe Kennedy , Dietrich Janan , Cheyip Mireille , Khanyile Nompumelelo , Doherty Tanya , Gray Glenda E
Published: February 2020

Background: While HIV Testing Services (HTS) have increased, many South Africans have not been tested. Non-communicable diseases (NCDs) are the top cause of death worldwide. Integrated NCD-HTS could be a strategy to control both epidemics. Healthcare service strategies depends partially on positive user experience. We investigated client satisfaction of services and clinic flow time of an integrated NCD-HTS clinic. Methods: This prospective, cross-sectional study evaluated HTS client satisfaction with an HTS clinic at two phases. Phase 1 (February–June 2018) utilised standard HTS services: counsellor-led height/weight/BP measurements, HIV rapid testing, and symptoms screening for sexually transmitted infections/Tuberculosis. Phase 2 (June 2018–March 2019) further integrated counsellor-led obesity screening (BMI/abdominal measurements), rapid cholesterol/glucose testing; and nurse-led Chlamydia and HPV/cervical cancer screening. Socio-demographics, proportion of repeat clients, clinic flow time, and client survey data (open/closed-ended questions using five-point Likert scale) are reported. Fisher’s exact test, chi-square analysis, Kruskal Wallis test conducted comparisons. Multiple linear regression determined predictors associated with clinic time. Content thematic analysis was conducted for free response data. Results: 284 and 333 participants were from Phase 1 and 2, respectively (N=617). Phase 1 participants were significantly older (median age 36.5 (28.0–43.0) years vs. 31.0 (25.0–40.0) years; p=0.0003), divorced/widowed (6.7%, [n=19/282] vs. 2.4%, [n=8/332]; p=0.0091); had tertiary education (27.9%, [n=79/283] vs. 20.1%, [n=67/333]; p=0.0234); and were less female (53.9%, [n=153/284] vs 67.6%, [n=225/333]; p=0.0005), compared to Phase 2. Phase 2 had 10.2% repeat clients (n=34/333), and 97.9% (n=320/327) were ‘ very satisfied’ with integrated NCD-HTS, despite standard HTS having significantly shorter median time for counsellor-led HTS (36.5, interquartile range [IQR]: 31.0-45.0 vs. 41.5, IQR: 35.0-51.0; p<0.0001). Phase 2 associations with longer clinic time were clients living together/married (est=6.548; p=0.0467), more tests conducted (est=3.922; p<0.0001), higher overall satisfaction score (est=1.210; p=0.0201). Matriculated clients experienced less clinic time (est=-7.250; p=0.0253). Conclusions: It is possible to integrate counsellor-led NCD rapid testing into standard HTS within historical HTS timeframes, yielding client satisfaction. Rapid cholesterol/glucose testing should be integrated into standard HTS. Research is required on the impact of cervical cancer/HPV screenings to HTS clinic flow to determine if it could be scaled up within the public sector.
Cost-effectiveness analysis of atezolizumab in advanced triple-negative breast cancer
Authors: Phua Lee Cheng , Lee Soo Chin , Ng Kwong , Aziz Mohamed Ismail Abdul
Published: February 2020

Background The IMpassion130 trial demonstrated that adding atezolizumab to nanoparticle albumin-bound (nab)-paclitaxel improved the survival of patients with untreated, advanced, programmed death ligand 1 (PDL1)-positive triple-negative breast cancer (TNBC). In view of the high cost of immunotherapy, it is important to examine its value with respect to both benefits and costs. In this study, the cost-effectiveness of atezolizumab/nab-paclitaxel combination therapy relative to nab-paclitaxel monotherapy was evaluated for the first-line treatment of advanced, PDL1-positive TNBC, from a healthcare system perspective. Methods A three-state partitioned-survival model was developed to compare the clinical and economic outcomes of treatment with atezolizumab/nab-paclitaxel combination therapy with nab-paclitaxel monotherapy in patients with advanced TNBC. Clinical data were obtained from the IMpassion130 trial and extrapolated to 5 years. Health state utilities were retrieved from the literature, while direct costs were sourced from public healthcare institutions in Singapore. The primary outcomes of the model were life years (LYs), quality-adjusted LYs (QALYs), costs and incremental cost-effectiveness ratios (ICERs). One-way and probabilistic sensitivity analyses and scenario analyses were conducted to explore the impact of specific assumptions and uncertainties. Results Adding atezolizumab to nab-paclitaxel resulted in an additional 0.361 QALYs (0.636 LYs) at an ICER of S$324,550 per QALY gained. The ICER remained high at $67,092 per QALY even when atezolizumab was priced zero. One-way sensitivity analysis showed that the ICER was most sensitive to variations in the cost of atezolizumab and the time horizon. Scenario analyses confirmed that the combination therapy was unlikely to be cost-effective even under extremely favourable assumptions. Conclusions Given the exceedingly high ICER, adding atezolizumab to nab-paclitaxel was unlikely to represent a cost-effective use of healthcare resources for the treatment of advanced PDL1-positive TNBC. Our findings will be useful in informing funding policy decisions alongside other considerations such as comparative effectiveness, unmet need and budget impact.
How well does Malaysia achieve value for money in public sector purchasing of medicines? Evidence from medicines procurement prices from 2010 to 2014
Authors: Ham Nurhafiza Md , Perera Prasadini N , Rannan-Eliya Ravindra P
Published: February 2020

Background Malaysia’s public healthcare sector provides a greater volume of medicines at lower overall cost, indicating its importance in providing access to medicines for Malaysians. However, the Ministry of Health (MOH), as the main healthcare provider, has concerns about the continuous increase in the public sector medicines budget, and achieving efficiencies in medicines procurement is an important goal. The objectives of this study were to assess the overall trend in public sector pharmaceutical procurement efficiency from 2010 to 2014, and determine if the three different ways in which MOH procures medicines influences efficiency.Methods We matched medicines from the public sector procurement report by medicine formulation to medicines with a Management Sciences for Health (MSH) International Reference Price (IRP) for each year. Price ratios were calculated, and utilizing the information on quantity and expenditure for each product, summary measures of procurement efficiency were reported as quantity- and expenditure-weighted average price ratios (WAPRs) for each year. Utilizing MOH procurement data to obtain information on procurement type, a multiple regression analysis, controlling for a number of factors that can influence prices, assessed whether procured efficiency (relative to IRPs) differed by MOH procurement type.Results Malaysia’s public sector purchased medicines at two to three times the IRP throughout the study period. However, procurement prices were relatively stable in terms of WAPRs each year (2.2 and 3.2 in 2010 to 1.9 and 2.9 in 2014 for quantity and expenditure WAPRs, respectively). Procurement efficiency did not vary between the three different methods of MOH procurement. Procurement efficiency of both imported innovators and imported generics were significantly lower ( P <0.001 and P <0.01) than local generic products, and medicine source and category influenced the procurement efficiency of each MOH procurement mechanism.Conclusion The design of different medicines procurement mechanisms, along with the balance of interests that Malaysia has sought to achieve in its public procurement procedures, have not been able to achieve lower public sector medicines procurement prices (relative to IRP). Introducing pooled procurement options along with continuous monitoring of procurement efficiency and exploring ways to improve price competition among local and foreign suppliers is recommended.
Catastrophic costs of Tuberculosis care in a population with internal migrants in China
Authors: Jiang Qi , Lu Liping , Hong Jianjun , Jin Xiaoping , Gao Qian , Bang Heejung , DeRiemer Kathryn , Yang Chongguang
Published: February 2020

Background Although a free diagnosis and baseline treatment package was offered for tuberculosis (TB), hidden costs incurred by patients and their households could worsen their socio-economic and health status, particularly for migrants. We estimated the prevalence of catastrophic cost of TB patients and its associated factors in an urban population with internal migrants in China. Methods A cross-sectional survey was conducted to enroll culture-confirmed pulmonary TB patients in Songjiang district, Shanghai, between December 1, 2014, and December 31, 2015. Consenting participants completed a questionnaire, which collected direct and indirect costs before and after the diagnosis of TB. The catastrophic cost was defined as the annual expenses of TB care that exceeds 20% of total household income. We used logistic regression to identify factors associated with catastrophic costs. Results Overall, 248 drug-susceptible TB patients were enrolled, with 70% (174 of 248) of them being internal migrants. Migrant patients were significantly younger compared to resident patients. The total costs were 25,824 ($3,689) and 13,816 ($1,974) Chinese Yuan (RMB) for resident and internal migrant patients, respectively. The direct medical cost comprised about 70% of the total costs among both migrant and resident patients. Overall, 55% (132 of 248) of patients experienced high expenses ( > 10% of total household income), and 22% (55 of 248) experienced defined catastrophic costs. However, the reimbursement for TB care only reduced the prevalence of catastrophic costs to 20% (49 of 248). More than half of the internal migrants had no available health insurance (52%, 90 of 174). Hospitalizations, no available insurance, and older age contributed significantly to the occurrence of catastrophic costs. Conclusions. The catastrophic cost of TB service cannot be overlooked, despite the free policy. Migrants have difficulties benefiting from health insurance in urban cities. Interventions, including expanded medical financial assistance, are needed to secure universal TB care.
Parkinson´s related protein DJ-1 is involved in aberrant cell cycle re-entry through Cdk5
Authors: López-Grueso Mª José , Padilla Carmen Alicia , Bárcena José Antonio , Requejo-Aguilar Raquel
Published: February 2020

DJ-1 is a multifunctional protein involved in Parkinson disease (PD) that can act as antioxidant, molecular chaperone, protease, glyoxalase and transcriptional regulator. However, the exact mechanism by which DJ-1 dysfunction contributes to development of Parkinson´s disease remains elusive. Here, using a comparative proteomic analysis between normal cortical neurons and neurons lacking DJ-1, we show that this protein is involved in cell cycle checkpoints disruption as a consequence of increased amount of p-Tau and a-synuclein proteins, altered signalling pathways, as the phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK), and deregulation of cyclin-dependent kinase 5 (Cdk5). Cdk5 is normally involved in dendritic growth, axon formation and the establishment of synapses, but can also contribute to cell cycle progression, as in our case, in pathological conditions. In addition, we observed a decrease in proteasomal activity, probably due to Tau phosphorylation that can also lead to activation of mitogenic signalling pathways. Taken together, our findings indicate, for the first time, that aborted cell cycle re-entry could be at the onset of DJ-1 associated PD. Thereby, new approaches targeting cell cycle re-entry can be envisaged to improve current therapeutic strategies.
High-resolution imaging of autophagosome formation by LC3 and ATG12 in cells using scanning electron-assisted dielectric microscopy
Authors: Okada Tomoko , Ogura Toshihiko
Published: February 2020

Background Autophagy is an intracellular self-eating system that plays a central role in cellular recycling. The formation of functional autophagosomes depends on several autophagy- related proteins, including LC3 and Atg12. To analyse an autophagy system, it is essential to precisely examine the cellular functions of cells in liquid condition. For this purpose, we have developed a novel scanning electron-assisted dielectric microscope (SE-ADM) for nanoscale observations of intact cells in aqueous conditions. Results Here, we first show that our SE-ADM system observes LC3- and Atg12-containing autophagosomes in cells labelled with antibody-binding gold nano-colloids in medium. We observe that during autophagosome formation, Atg12 localises along the actin mesh structure, whereas LC3 forms arcuate or circular alignments. Our system also detects the different distribution properties of LC3 and Atg12. Atg12 is broadly distributed, whereas LC3 is localised over a smaller range. These differences in spatial-distribution manifest as differently sized spots on fluorescence optical microscopy. Conclusion The direct SE-ADM observations of living cells incubated with nanoparticles in a medium may be useful for analysing various cell functions.
Surgical outcomes and survival for T4 gastric cancer extending to the transverse colon
Authors: Wang Gang-Cheng , Gao Chong-Qing , Wang You-cai , Lv Hui-Fang , Chen Bei-Bei , Nie Cai-Yun , Chen Xiao-Bing , Liu Yingjun
Published: February 2020

Purpose Extended multi-organ resection for locally advanced (T4) gastric cancer remains controversial. Herein we aimed to evaluate the surgical outcomes and survival of patients with T4 gastric cancer extending to the transverse colon. Materials and Methods Between 2011 and 2015, forty patients had undergone curative resection for T4 gastric cancer extending to the transverse colon. Patient characteristics, related complications, long-term survival, and prognostic factors for T4 gastric cancer were analyzed. Results ost-operative morbidity occurred in 5 (12.5%) patients. The 1-, 3-, and 5-year overall survival rates were 75.0%, 49.2%, and 36.9%, respectively. Univariate analysis revealed that tumor size ( P =0.049), advanced T stage ( P =0.013), and lymph node metastasis ( P =0.006) are poor prognostic factors of overall survival. Based on multivariate analysis, advanced T stage and lymph node metastasis were identified as independent prognosis factors. Conclusions Patients with T4 gastric cancer extending to the transverse colon might benefit from curative resection with acceptable morbidity and mortality.
A nomogram to predict skip metastasis in papillary thyroid cancer
Authors: Ouyang Qianhui , Wang Wenlong
Published: February 2020

Background Skip metastases are defined as lateral lymph node metastasis (LNM) without the involvement of central LNM in papillary thyroid cancer (PTC), and it is difficult to predict in clinical practice. Our study aimed to investigate the risk factors of skip metastasis and establish a nomogram for predicting the probability of skip metastasis in PTC patients. Patients and Methods A total of 378 consecutive PTC patients with clinically suspected LNM who underwent modified radical neck dissection (MRND) from March 2018 to July 2019 were enrolled in our hospital, Univariate and multivariate analyses were used to examine risk factors of skip metastasis, and a nomogram prediction model was established and internal validated. Results The incidence of skip metastasis was 11.9% (45/378). Primary tumor size ≦1cm(OR=2.703, 95%CI,1342-5.464; P =0.005 ), Age(OR=1.051, 95%CI, 1.017-1.805, P =0.005), Primary tumor location in the upper portion(OR=6.799, 95%CI, 2.710-17.060, P < 0.001)were found to be independent risk factors for skip metastasis in PTC patients. A nomogram based upon these predictors performed well. With an area under the curve (AUC) of 0.806 (95%CI,0.736-0.876) and the P value of the Hosmer-Lemeshow goodness of fit test was 0.66, Decision curve analysis revealed that nomogram was clinically useful. Conclusion Based on the risk factors of skip metastasis and established a high-performance nomogram, which can provide an individual risk assessment and guide treatment decisions for patients.
Evaluating 10 years of state-funded GP training in GP offices in Switzerland
Authors: Baumann Kim , Lindemann Fanny , Diallo Beatrice , Rozsnyai Zsofia , Streit Sven
Published: February 2020

Background Switzerland lacks future general practitioners (GPs). Residents who wished to specialize as general practitioners were formerly trained solely in hospital settings. To better prepare and also attract more young doctors to become GPs, the canton of Bern has implemented a partly state-funded vocational training program in GP practices. Our study examines the efficacy of this 10-year program, identifies factors that positively influence residents in their decision to become a GP and the distribution of new GPs in the canton of Bern, who had taken part in the traineeship. Methods This cross-sectional survey among all residents, who participated in a traineeship in general practice from 2008 to 2017 in the canton of Bern asked if residents had taken a subsequent career choice as a GP and if so in which region. Residents scored the importance of their traineeship and their mentor’s influence on becoming a GP. By using zip codes of work area of respondents already working as GPs and matching it with population census data, we could obtain the distribution of GPs on a per capita basis. Results Out of 165 residents who participated in a traineeship, 151 (92%) completed our survey. 81% had chosen a career as a GP or were on track to become a GP. Almost half of the participants became GPs in the offices of their mentors. Our respondents emphasized the importance of their mentors influence as well as the training program in their decision-making to become a GP. Most mentioned benefits of being a GP were broad field of medical care (37%) and a fulfilling doctor-patient relationship (34%). We could show an increase in GP practices in the canton of Bern, not only in urban but also accordingly in rural areas. Conclusions Most residents continued subsequent careers as general practitioners after having completed a GP traineeship, with almost half of them in the region of their training. A vocational training program helped motivating young doctors to become GPs and underserved regions of the canton of Bern to gain new GPs.
Recent Trends and Variations in General Practitioners’ Involvement in Accident Care in Switzerland: an Analysis of Claims Data
Authors: Höglinger Marc , Knöfler Fabio , Stosch Rita Schaumann-von , Scholz Stefan M. , Eichler Klaus
Published: February 2020

BACKGROUND As in other countries, there is concern and some fragmentary evidence that GPs’ central role in the Swiss healthcare system might be changing or even be in decline. Our study gives a systematic account of GPs’ involvement in accident care from 2008 to 2016 and identifies changes in GPs’ involvement in this typical field of primary care: how frequently GPs were involved along the care pathway, to what extent they figured as initial care provider, and what their role in the care pathway was. METHODS Using a claims dataset from the largest Swiss accident insurer with two million accident cases, we constructed individual care pathways, i.e., when and from which providers patients received care. We calculated probabilities for the involvement of various care provider groups, for initial care provision, and for the role of GPs in patients’ care pathways, adjusted for injury and patient characteristics using multinomial regression. RESULTS In 2014, GPs were involved in 70% of all accident cases requiring outpatient care but no inpatient stay, and provided initial care in 56%. While involvement stayed at about the same level for accidents occurring from 2008 to 2014, the share of accidents where GPs provided initial care decreased by 4 percentage points. The share of cases where GPs acted as sole care provider decreased by 7 percentage points down to 44%. At the same time, accident cases involving care from an ED at any point in time increased from 38% to 46% and the share receiving initial care from an ED from 30 to 35 percentage points – apparently substituting for the declining involvement of GPs in initial care. GPs’ involvement in accident care is higher in rural compared to urban regions, among elderly compared to younger patients, and among Swiss compared to non-Swiss citizens. CONCLUSIONS GPs play a key role in accident care with considerable variation depending on region and patient profile. From 2008 to 2014, there is a remarkable decline in GPs’ provision of initial care after an accident. This is a strong indication that the GPs’ role in the Swiss healthcare system is changing.
ZNF213 facilitates ER alpha signaling in breast cancer cells
Authors: Zhuang Ting , Yang Huijie , Zhao Wuchen , Li Xin , Niu Zhiguo , Huang Qingsong
Published: February 2020

Background Breast cancer is the most common women malignancy worldwide, while estrogen receptor alpha positive type accounts for two third of all breast cancers. Although ER alpha positive breast cancer could be effectively controlled by endocrine therapy, more than half of the cases could develop endocrine resistance, making it an important clinical issue in breast cancer treatment. Thus, decoding the detailed mechanism, which controls ER alpha signaling activation and ER alpha protein stability, is of great importance for the improvement of breast cancer therapy. Methods ZNF213 and ER alpha protein expression level were measured by western blot, while ER alpha target genes were determined by QPCR. WST-1 assay was used to measure cell proliferation. RNA sequence was performed by Ingenuity pathway analysis. The ER alpha signaling activities were measured with luciferase assay, QPCR and western blotting. Protein stability assay and ubiquitin assay were used to determine ER alpha protein degradation and ubiquitination. The immuno-precipation was utilized to determine ER alpha and ZNF213 interaction. The ubiquitin-based immuno-precipitation assay was sued to detect specific ubiquitination manner on ER alpha. The prognostic data of ZNF213 was derived from public available database. Results Here, we identified ZNF213 as a novel zinc finger protein, which modulates ER alpha protein. ZNF213 expression correlates with poor outcome in endocrine treated patients. ZNF213 depletion inhibits ER alpha signaling and proliferation in breast cancer cells. Further mechanistic studies show that ZNF213 is located in cytosol and nuclear, which modulates ER alpha stability via inhibiting ER alpha K48-linked ubiquitination. Conclusions Our study reveals an interesting post-translational mechanism between ER alpha and ZNF213 in breast cancer. Targeting ZNF213 could be an appealing strategy for ER alpha positive breast cancer.
Magnetic targeting enhances the cutaneous wound healing effects of human mesenchymal stem cell-derived iron oxide exosomes
Authors: Li Xiuying , Wang Ying , Li Binxi , Li Jing , Wei Zhenhong , Lv Huiying , Wu Liya , Zhang Hao , Yang Bai , Xu Xiaohua , Jiang Jinlan
Published: February 2020

Human mesenchymal stem cell (MSC)-derived exosomes (Exos) are a promising therapeutic agent for cell-free regenerative medicine. However, their poor organ-targeting ability and therapeutic efficacy have been found to critically limit their clinical applications. In the present study, we fabricated iron oxide nanoparticle (NP)-labeled exosomes (Exo+NPs) from NP-treated MSCs and evaluated their therapeutic efficacy in a clinically relevant model of skin injury. We found that the Exos could be readily internalized by human umbilical vein endothelial cells (HUVECs), and significantly promoted their proliferation, migration, and angiogenesis both in vitro and in vivo . Moreover, the protein expression of proliferative markers (Cyclin D1 and Cyclin A2), growth factors (VEGFA), and migration chemokines (CXCL12) was significantly upregulated after Exo treatment. Unlike the Exos prepared from untreated MSCs, the Exo+NPs contained NPs that acted as a magnet-guided navigation tool. The in vivo systemic injection of Exo+NPs with magnetic guidance significantly increased the number of Exo+NPs that accumulated at the injury site. Furthermore, these accumulated Exo+NPs significantly enhanced endothelial cell proliferation, migration, and angiogenic tubule formation in vivo ; moreover, they reduced scar formation, and increased CK19, PCNA, and collagen expression in vivo . Collectively, these findings confirm the development of therapeutic efficacy-potentiated extracellular nanovesicles and demonstrate their feasibility in cutaneous wound repair.
Contradictory responses of the microcirculation to changes in extracorporeal membrane oxygenation pump flow in patients on venoarterial extracorporeal membrane oxygenation: a prospective observational study
Authors: Wei Tzu-Jung , Wang Chih-Hsien , Chan Wing-Sum , Yeh Yi-Chun , Lai Chien-Heng , Chao Anne , Huang Chi-Hsiang , Wang Ming-Jiuh , Cheng Ya-Jung , Chen Yih-Sharng , Ince Can , Lin Tzu-Yu , Yeh Yu-Chang
Published: February 2020

Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) pump flow is crucial for maintaining tissue and organ perfusion in patients with cardiogenic shock. Determining the optimal VA-ECMO pump flow rate to maintain adequate tissue perfusion remains a clinical challenge. Poor microcirculation is associated with higher mortality in patients using VA-ECMO. Change in VA-ECMO pump flow is expected to result in a coherent change in microcirculatory blood flow, but this has not been investigated. This study investigated the effect of altering VA-ECMO pump flow rate on sublingual microcirculation. Methods: Sublingual microcirculation images were recorded using an incident dark-field hand held vital microscope at two time points, within 24 h (T1) and at 24-48 h (T2) after VA-ECMO placement. Microcirculation was measured before and 5 minutes after the changes in VA-ECMO pump flow rate at each time point. Events of changing VA-ECMO pump flow rate at T1 and T2 were divided into four groups according to changes in perfused vessel density (PVD): Group A, increased pump flow rate and increased or sustained PVD; Group B, increased pump flow rate and decreased PVD; Group C, decreased pump flow rate and increased or sustained PVD; and Group D, decreased pump flow rate and decreased PVD. The microcirculatory parameters, clinical parameters, and prognosis of each subgroup were recorded. Clinical parameters on 14-day and 28-day survivors and non-survivors were also compared. Results: A total of 25 patients were enrolled, and 38 events with good-quality images at T1 and T2 were categorized. Opposing response of microcirculation was observed in 43.5% of events when VA-ECMO pump flow rate was increased. Microcirculation was decreased in 33.4% of events when VA-ECMO pump flow rate was reduced. No predictive values in microcirculatory or macrocirculatory parameters before changing VA-ECMO pump flow rate were identified. Conclusions: Changes in VA-ECMO pump flow rate may have opposing effects on sublingual microcirculatory functional capillary density. We suggest that tandem measurements of microcirculation before and after altering the VA-ECMO pump flow may help to ensure optimal tissue perfusion.
Predictive factors for successful INTELLiVENT-ASV® use: A retrospective observational study
Authors: Katayama Shinshu , Tonai Ken , Shima Jun , Koyama Kansuke , Nunomiya Shin
Published: February 2020

Background: INTELLiVENT-ASV® (I-ASV) is a closed-loop ventilation mode that automatically controls the ventilation settings. Although a number of studies have reported the usefulness of I-ASV, the clinical situations in which it may be useful have not yet been clarified. We aimed to report our initial 3 years of experience using I-ASV, particularly the clinical conditions and the technical and organizational factors associated with its use. Furthermore, we evaluated the usefulness of I-ASV and determined the predictive factors for successful management with I-ASV. Methods: This single-center, retrospective observational study included patients who were ventilated using the Hamilton G5® ventilator (Hamilton Medical AG, Rhäzüns, Switzerland) from January 2016 to December 2018. The patients were categorized into the “I-ASV success” group and “I-ASV failure” group (those receiving mechanical ventilation with I-ASV along with any other mode). Multivariate analysis was performed to identify factors associated with successful I-ASV management.Results : Of the 189 patients, 135 (71.4%) were categorized into the I-ASV success group. In the I-ASV success group, the reasons for ICU admission included post-elective surgery (94.1%), post-emergent surgery (81.5%), and other medical reasons (55.6%). The main reasons for not using I-ASV included strong inspiratory effort and asynchrony. The Acute Physiology and Chronic Health Evaluation (APACHE) II score was an independent predictive factor for successful management with I-ASV, with an odds ratio of 0.92 (95% confidential interval 0.87–0.96, P = 0.0006). The area under the receiver operating curve for the APACHE II score was 0.722 (cut-off: 25). Conclusions : In this study, we found that 71.4% of the fully mechanically ventilated patients could be managed successfully with I-ASV. The APACHE II score was an independent factor that could help predict the successful management of I-ASV. To improve I-ASV management, it is necessary to focus on patient-ventilator interactions.
Morphological changes of the anterior alveolar bone due to retraction of anterior teeth: a retrospective study
Authors: Sun Qiannan , Chen Si , Lu Wenhsuan , Zhang Yunfan , Peng Liying , Han Bing
Published: February 2020

Background: The morphology of the anterior alveolar bone may change after the retraction of incisors in premolar extraction cases in orthodontics.Methods: Pre- (T0) and post-treatment (T1) lateral cephalograms of 477 subjects in the maxilla and 226 subjects in the mandible who underwent the orthodontic treatment with extraction of 2 premolars in upper or lower arches were included. Alveolar bone width and height in both the maxillary and mandible incisor area were measured at T0 and T1 respectively. By superimposing the T0 and T1 cephalometric tracings, changes of points A and B, and the movement of the incisors were also measured.Results: The alveolar bone width (ABW) showed a significant decrease in both maxilla and mandible (P<0.001) except the labial side of the mandible, which exhibited slight increase, though statistically insignificant (P>0.05). The alveolar bone height (ABH) showed a significant increase in the labial side of maxilla and a significant decrease in the lingual side of maxilla and mandible. A strong positive correlation was observed between incisor movement and position changes of points A and B both in the horizontal and vertical direction. Conclusions: Anterior alveolar bone width and height generally decreased after orthodontic treatment. Incisor retraction led to a significant position changes of points A and B.