bluuebunny/crossref_metadata_2025 huggingface dataset:
Young medical doctors’ perspectives on professionalism: a qualitative study conducted in public hospitals in Pakistan
Authors: Jalil Aisha , Mahmood Qaisar Khalid , Fischer Florian
Published: September 2020

Background

Professionalism is amongst the major dimensions determining the competence of medical doctors. Poor professionalism affects the overall outcome of healthcare services. This study explores the perspectives of young medical doctors on professionalism in Pakistan.

Methods

A qualitative study based on in-depth interviews was conducted with 60 young medical doctors, aged less than 40 years, who had studied medicine in Pakistani universities, were Pakistani nationals, and were employed at various hierarchical levels, from house officer to consultant specialist, in public tertiary hospitals in Pakistan. The respondents were identified through a multistage maximum heterogeneity sampling strategy. A semi-structured interview guide was developed based on a previous extensive literature review. Written consent was obtained from the hospitals and study participants. Qualitative thematic analysis was applied to analyse the data.

Results

The data analysis revealed that rigidity of opinions, unacceptability of contrasting perspectives, false pride, and perceived superiority over other professions and patients were major components of poor medical professionalism. Most of the young doctors believed that there is no need to include professionalism and humanity course modules in the medical curriculum, because topics related to social sciences are deemed irrelevant to medicine and judged to be common sense. The doctors recognised good professionalism in themselves, while reporting unprofessional behaviour demonstrated by their colleagues and paramedics. Other factors contributing to poor medical professionalism included the use of social media applications during duty hours, ridiculing patients, substance use such as smoking cigarettes in the office, referrals of complicated cases to other hospitals, freeing up beds before holidays, lack of cooperation from paramedical staff, and inadequate role models.

Conclusions

Poor medical professionalism among young doctors needs to be addressed by policymakers. There is a need to revisit the medical curriculum to strengthen professionalism. It is essential to develop the qualities of tolerance, teachability, and acceptance in doctors in order to facilitate interprofessional collaborations and avoid medical errors.
Geographical and socioeconomic inequalities in the utilization of maternal healthcare services in Nigeria: 2003–2017
Authors: Okoli Chijioke , Hajizadeh Mohammad , Rahman Mohammad Mafizur , Khanam Rasheda
Published: September 2020

Background

Maternal mortality has remained a challenge in many low-income countries, especially in Africa and in Nigeria in particular. This study examines the geographical and socioeconomic inequalities in maternal healthcare utilization in Nigeria over the period between 2003 and 2017.

Methods

The study used four rounds of Nigeria Demographic Health Surveys (DHS, 2003, 2008, 2013, and 2018) for women aged 15–49 years old. The rate ratios and differences (RR and RD) were used to measure differences between urban and rural areas in terms of the utilization of the three maternal healthcare services including antenatal care (ANC), facility-based delivery (FBD), and skilled-birth attendance (SBA). The Theil index (T), between-group variance (BGV) were used to measure relative and absolute inequalities in the utilization of maternal healthcare across the six geopolitical zones in Nigeria. The relative and absolute concentration index (RC and AC) were used to measure education-and wealth-related inequalities in the utilization of maternal healthcare services.

Results

The RD shows that the gap in the utilization of FBD between urban and rural areas significantly increased by 0.3% per year over the study period. The Theil index suggests a decline in relative inequalities in ANC and FBD across the six geopolitical zones by 7, and 1.8% per year, respectively. The BGV results do not suggest any changes in absolute inequalities in ANC, FBD, and SBA utilization across the geopolitical zones over time. The results of the RC and the AC suggest a persistently higher concentration of maternal healthcare use among well-educated and wealthier mothers in Nigeria over the study period.

Conclusion

We found that the utilization of maternal healthcare is lower among poorer and less-educated women, as well as those living in rural areas and North West and North East geopolitical zones. Thus, the focus should be on implementing strategies that increase the uptake of maternal healthcare services among these groups.
Representativeness of personality and involvement preferences in a web-based survey on healthcare decision-making
Authors: Birkeland Søren , Linkhorst Thea , Haakonsson Anders , Barry Michael John , Möller Sören
Published: September 2020

Background

Obtaining a sample that is representative of the group of interest is of utmost importance in questionnaire studies. In a survey using a state authorized web-portal for citizen communication with authorities, we wanted to investigate the view of adult men on patient involvement in health care decision-making regarding Prostate-Specific Antigen test for prostatic cancer. In this paper, we report on sample characteristics and representativeness of our sample in terms of personality and baseline involvement preferences.

Methods

We compared personality profiles (BFI-10) and baseline healthcare decision-making preferences (CPS) in our sample (n = 6756) to internationally available datasets. Pooled data from a) US, UK, Canada, Australia, and New Zealand (n = 1512), b) Germany, Netherlands, Switzerland, and Belgium (n = 1136), and c) Norway, Sweden, Finland, and Denmark (n = 1313) were used for BFI-10 comparisons. Regarding CPS, we compared our sample with three previous datasets relating to decision-making in cancer (n = 425, 387, and 199).

Results

Although statistically significant differences particularly appeared in large dataset comparisons, sample BFI-10 and CPS profiles mostly were within the range of those previously reported. Similarity was greatest in BFI-10 comparisons with group a) where no statistically significant difference could be established in factors ‘agreeableness’ and ‘neuroticism’ (p = .095 and .578, respectively).

Conclusion

Despite some variation, our sample displays personality and baseline preference profiles that are generally similar to those described in previous international studies. For example, this was the case with the BFI-10 ‘agreeableness’ measure (incl. trust and fault-finding items), an important factor in healthcare decision-making.
Call order within vocal sequences of meerkats contains temporary contextual and individual information
Authors: Rauber Ramona , Kranstauber Bart , Manser Marta B.
Published: September 2020

Background

The ability to recombine smaller units to produce infinite structures of higher-order phrases is unique to human language, yet evidence of animals to combine multiple acoustic units into meaningful combinations increases constantly. Despite increasing evidence for meaningful call combinations across contexts, little attention has been paid to the potential role of temporal variation of call type composition in longer vocal sequences in conveying information about subtle changes in the environment or individual differences. Here, we investigated the composition and information content of sentinel call sequences in meerkats (Suricata suricatta). While being on sentinel guard, a coordinated vigilance behaviour, meerkats produce long sequences composed of six distinct sentinel call types and alarm calls. We analysed recordings of sentinels to test if the order of the call types is graded and whether they contain additional group-, individual-, age- or sex-specific vocal signatures.

Results

Our results confirmed that the six distinct types of sentinel calls in addition to alarm calls were produced in a highly graded way, likely referring to changes in the perceived predation risk. Transitions between call types one step up or down the a priory assumed gradation were over-represented, while transitions over two or three steps were significantly under-represented. Analysing sequence similarity within and between groups and individuals demonstrated that sequences composed of the most commonly emitted sentinel call types showed high within-individual consistency whereby adults and females had higher consistency scores than subadults and males respectively.

Conclusions

We present a novel type of combinatoriality where the order of the call types contains temporary contextual information, and also relates to the identity of the caller. By combining different call types in a graded way over long periods, meerkats constantly convey meaningful information about subtle changes in the external environment, while at the same time the temporal pattern of the distinct call types contains stable information about caller identity. Our study demonstrates how complex animal call sequences can be described by simple rules, in this case gradation across acoustically distinct, but functionally related call types, combined with individual-specific call patterns.
Exosomal microRNAs are novel circulating biomarkers in cigarette, waterpipe smokers, E-cigarette users and dual smokers
Authors: Singh Kameshwar P. , Maremanda Krishna P. , Li Dongmei , Rahman Irfan
Published: September 2020

Background

Electronic cigarettes (e-cigs) vaping, cigarette smoke, and waterpipe tobacco smoking are associated with various cardiopulmonary diseases. microRNAs are present in higher concentration in exosomes that play an important role in various physiological and pathological functions. We hypothesized that the non-coding RNAs transcript may serve as susceptibility to disease biomarkers by smoking and vaping.

Methods

Plasma exosomes/EVs from cigarette smokers, waterpipe smokers and dual smokers (cigarette and waterpipe) were characterized for their size, morphology and TEM, Nanosight and immunoblot analysis. Exosomal RNA was used for small RNA library preparation and the library was quantified using the High Sensitivity DNA Analysis on the Agilent 2100 Bioanalyzer system and sequenced using the Illumina NextSeq 500 and were converted to fastq format for mapping genes.

Results

Enrichment of various non-coding RNAs that include microRNAs, tRNAs, piRNAs, snoRNAs, snRNAs, Mt-tRNAs, and other biotypes are shown in exosomes. A comprehensive differential expression analysis of miRNAs, tRNAs and piRNAs showed significant changes across different pairwise comparisons. The seven microRNAs that were common and differentially expressed of when all the smoking and vaping groups were compared with non-smokers (NS) are hsa-let-7a-5p, hsa-miR-21-5p, hsa-miR-29b-3p, hsa-let-7f-5p, hsa-miR-143-3p, hsa-miR-30a-5p and hsa-let-7i-5p. The e-cig vs. NS group has differentially expressed 5 microRNAs (hsa-miR-224-5p, hsa-miR-193b-3p, hsa-miR-30e-5p, hsa-miR-423-3p, hsa-miR-365a-3p, and hsa-miR-365b-3p), which are not expressed in other three groups. Gene set enrichment analysis of microRNAs showed significant changes in the top six enriched functions that consisted of biological pathway, biological process, molecular function, cellular component, site of expression and transcription factor in all the groups. Further, the pairwise comparison of tRNAs and piRNA in all these groups revealed significant changes in their expressions.

Conclusions

Plasma exosomes of cigarette smokers, waterpipe smokers, e-cig users and dual smokers have common differential expression of microRNAs which may serve to distinguish smoking and vaping subjects from NS. Among them has-let-7a-5p has high sensitivity and specificity to distinguish NS with the rest of the users, using ROC curve analysis. These findings will pave the way for the utilizing the potential of exosomes/miRNAs as a novel theranostic agents in lung injury and disease caused by tobacco smoking and vaping.
Dissecting the conformation of glycans and their interactions with proteins
Authors: Wang Sheng-Hung , Wu Tsai-Jung , Lee Chien-Wei , Yu John
Published: September 2020

The use of in silico strategies to develop the structural basis for a rational optimization of glycan-protein interactions remains a great challenge. This problem derives, in part, from the lack of technologies to quantitatively and qualitatively assess the complex assembling between a glycan and the targeted protein molecule. Since there is an unmet need for developing new sugar-targeted therapeutics, many investigators are searching for technology platforms to elucidate various types of molecular interactions within glycan-protein complexes and aid in the development of glycan-targeted therapies. Here we discuss three important technology platforms commonly used in the assessment of the complex assembly of glycosylated biomolecules, such as glycoproteins or glycosphingolipids: Biacore analysis, molecular docking, and molecular dynamics simulations. We will also discuss the structural investigation of glycosylated biomolecules, including conformational changes of glycans and their impact on molecular interactions within the glycan-protein complex. For glycoproteins, secreted protein acidic and rich in cysteine (SPARC), which is associated with various lung disorders, such as chronic obstructive pulmonary disease (COPD) and lung cancer, will be taken as an example showing that the core fucosylation of N-glycan in SPARC regulates protein-binding affinity with extracellular matrix collagen. For glycosphingolipids (GSLs), Globo H ceramide, an important tumor-associated GSL which is being actively investigated as a target for new cancer immunotherapies, will be used to demonstrate how glycan structure plays a significant role in enhancing angiogenesis in tumor microenvironments.
Navafenterol (AZD8871) in patients with mild asthma: a randomised placebo-controlled phase I study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of this novel inhaled long-acting dual-pharmacology bronchodilator
Authors: Jimenez Eulalia , Astbury Carol , Albayaty Muna , Wählby-Hamrén Ulrika , Seoane Beatriz , Villarroel Cristina , Pujol Helena , Bermejo Maria Jesus , Aggarwal Ajay , Psallidas Ioannis
Published: September 2020

Background

Navafenterol (AZD8871) is an inhaled long-acting dual-pharmacology muscarinic antagonist/β2-adrenoceptor agonist (MABA) in development for the treatment of obstructive airways diseases. The safety, tolerability, pharmacodynamics, and pharmacokinetics of navafenterol were investigated in patients with mild asthma.

Methods

This was a randomised, single-blind, placebo-controlled, single-ascending-dose study. Patients were randomly assigned to one of two cohorts which evaluated escalating doses of navafenterol (50–2100 μg) in an alternating manner over three treatment periods. The primary pharmacodynamic endpoint was the change from pre-dose baseline in trough forced expiratory volume in 1 s (FEV1) for each treatment period.

Results

Sixteen patients were randomised; 15 completed treatment. Data from all 16 patients were analysed. The maximum tolerated dose was not identified, and all doses of navafenterol were well tolerated. The most frequently reported treatment-emergent adverse events (TEAEs) were headache (n = 10, 62.5%) and nasopharyngitis (n = 7, 43.8%). No TEAEs were serious, fatal, or led to discontinuation, and no dose dependency was identified. Navafenterol demonstrated a dose-ordered bronchodilatory response with a rapid onset of action (within 5 min post-dose). Doses ≥200 μg resulted in improvements in trough FEV1 (mean change from baseline range 0.186–0.463 L) with sustained bronchodilation for 24–36 h. Plasma concentrations increased in a dose-proportional manner, peaking ~ 1 h post-dose, with a derived terminal elimination half-life of 15.96–23.10 h.

Conclusions

In this study navafenterol was generally well tolerated with a rapid onset of action which was sustained over 36 h.

Trial registration

ClinicalTrials.gov; No.: NCT02573155
Nrf2 protects against seawater drowning-induced acute lung injury via inhibiting ferroptosis
Authors: Qiu Yu-bao , Wan Bin-bin , Liu Gang , Wu Ya-xian , Chen Dan , Lu Mu-dan , Chen Jun-liang , Yu Ren-qiang , Chen Dao-zhen , Pang Qing-feng
Published: September 2020

Background

Ferroptosis is a new type of nonapoptotic cell death model that was closely related to reactive oxygen species (ROS) accumulation. Seawater drowning-induced acute lung injury (ALI) which is caused by severe oxidative stress injury, has been a major cause of accidental death worldwide. The latest evidences indicate nuclear factor (erythroid-derived 2)-like 2 (Nrf2) suppress ferroptosis and maintain cellular redox balance. Here, we test the hypothesis that activation of Nrf2 pathway attenuates seawater drowning-induced ALI via inhibiting ferroptosis.

Methods

we performed studies using Nrf2-specific agonist (dimethyl fumarate), Nrf2 inhibitor (ML385), Nrf2-knockout mice and ferroptosis inhibitor (Ferrostatin-1) to investigate the potential roles of Nrf2 on seawater drowning-induced ALI and the underlying mechanisms.

Results

Our data shows that Nrf2 activator dimethyl fumarate could increase cell viability, reduced the levels of intracellular ROS and lipid ROS, prevented glutathione depletion and lipid peroxide accumulation, increased FTH1 and GPX4 mRNA expression, and maintained mitochondrial membrane potential in MLE-12 cells. However, ML385 promoted cell death and lipid ROS production in MLE-12 cells. Furthermore, the lung injury became more aggravated in the Nrf2-knockout mice than that in WT mice after seawater drowning.

Conclusions

These results suggested that Nrf2 can inhibit ferroptosis and therefore alleviate ALI induced by seawater drowning. The effectiveness of ferroptosis inhibition by Nrf2 provides a novel therapeutic target for seawater drowning-induced ALI.
OIP5-AS1 contributes to tumorigenesis in hepatocellular carcinoma by miR-300/YY1-activated WNT pathway
Authors: Wang Yu , Dou Lei , Qin Yun , Yang Huiyuan , Yan Peng
Published: September 2020

Background

It has reported that long non-coding RNAs (lncRNAs) exerted regulatory functions by targeting specific genes through a competing endogenous RNA (ceRNA) pathway. LncRNA OIP5-AS1 has been identified as a tumor-enhancer in several tumor types. Nonetheless, its molecular mechanism in HCC remains to be masked.

Aim of the study

This study was aimed at exploring whether and how OIP5-AS1 exert functions in HCC.

Methods

qRT-PCR and western blot were employed for detecting gene expression. CCK-8, colony formation and EdU assays were implemented to evaluate the proliferative ability of HCC cells. Caspase-3 activity and flow cytometry analyses were implemented to determine cell apoptosis and cell cycle distribution. RNA pull down, ChIP, RIP and luciferase reporter assays explored the interplays between molecules.

Results

YY1 was upregulated in HCC cells, and silenced YY1 restrained HCC cell proliferation in vitro and hampered tumor growth in vivo. Later, we discovered that miR-300 could regulate WNT pathway via targeting YY1. Furthermore, OIP5-AS1 was identified as the sponge of miR-300 and promoted cell growth in HCC. Importantly, YY1 transcriptionally activate OIP5-AS1 in turn. Rescue experiments indicated that miR-300 inhibition or YY1 overexpression abrogated the inhibitive effect of OIP5-AS1 silencing on the malignant growth of HCC cells.

Conclusions

OIP5-AS1/miR-300/YY1 feedback loop facilitates cell growth in HCC by activating WNT pathway.
MicroRNA-221-3p is related to survival and promotes tumour progression in pancreatic cancer: a comprehensive study on functions and clinicopathological value
Authors: Wu Xuejiao , Huang Jia , Yang Zilin , Zhu Ying , Zhang Yongping , Wang Jiancheng , Yao Weiyan
Published: September 2020

Background

The microRNA miR-221-3p has previously been found to be an underlying biomarker of pancreatic cancer. However, the mechanisms of miR-221-3p underlying its role in pancreatic cancer pathogenesis, proliferation capability, invasion ability, drug resistance and apoptosis and the clinicopathological value of miR-221-3p have not been thoroughly studied.

Methods

Based on microarray and miRNA-sequencing data extracted from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), relevant literature, and real-time quantitative PCR (RT-qPCR), we explored clinicopathological features and the expression of miR-221-3p to determine its clinical effect in pancreatic cancer. Proliferation, migration, invasion, apoptosis and in vitro cytotoxicity tests were selected to examine the roles of mir-221-3p. In addition, several miR-221-3p functional analyses were conducted, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein–protein interaction (PPI) network analyses, to examine gene interactions with miR-221-3p.

Results

The findings of integrated multi-analysis revealed higher miR-221-3p expression in pancreatic cancer tissues and blood than that in para-carcinoma samples (SMD of miR-221-3p: 1.52; 95% CI 0.96, 2.08). MiR-221-3p is related to survival both in pancreatic cancer and pancreatic ductal adenocarcinoma patients. Cell experiments demonstrated that miR-221-3p promotes pancreatic cancer cell proliferation capability, migration ability, invasion ability, and drug resistance but inhibits apoptosis. Further pancreatic cancer bioinformatics analyses projected 30 genes as the underlying targets of miR-221-3p. The genes were significantly distributed in diverse critical pathways, including microRNAs in cancer, viral carcinogenesis, and the PI3K-Akt signalling pathway. Additionally, PPI indicated four hub genes with threshold values of 5: KIT, CDKN1B, RUNX2, and BCL2L11. Moreover, cell studies showed that miR-221-3p can inhibit these four hub genes expression in pancreatic cancer.

Conclusions

Our research revealed that pancreatic cancer expresses a high-level of miR-221-3p, indicating a potential miR-221-3p role as a prognosis predictor in pancreatic cancer. Moreover, miR-221-3p promotes proliferation capacity, migration ability, invasion ability, and drug resistance but inhibits apoptosis in pancreatic cancer. The function of miR-221-3p in the development of pancreatic cancer may be mediated by the inhibition of hub genes expression. All these results might provide an opportunity to extend the understanding of pancreatic cancer pathogenesis.
Melatonin and urological cancers: a new therapeutic approach
Authors: Pourhanifeh Mohammad Hossein , Hosseinzadeh Azam , Juybari Kobra Bahrampour , Mehrzadi Saeed
Published: September 2020

Urological cancers are responsible for thousands of cancer-related deaths around the world. Despite all developments in therapeutic approaches for cancer therapy, the absence of efficient treatments is a critical and vital problematic issue for physicians and researchers. Furthermore, routine medical therapies contribute to several undesirable adverse events for patients, reducing life quality and survival time. Therefore, many attempts are needed to explore potent alternative or complementary treatments for great outcomes. Melatonin has multiple beneficial potential effects, including anticancer properties. Melatonin in combination with chemoradiation therapy or even alone could suppress urological cancers through affecting essential cellular pathways. This review discusses current evidence reporting the beneficial effect of melatonin in urological malignancies, including prostate cancer, bladder cancer, and renal cancer.
Covid-19 in Israel: socio-demographic characteristics of first wave morbidity in Jewish and Arab communities
Authors: Birenbaum-Carmeli Daphna , Chassida Judith
Published: September 2020

Background

The first wave of the Covid-19 pandemic hit Israel in late February 2020. The present study examines patterns of the first wave of Covid-19 morbidity in Israel at the macro level, during the period of late February to early June 2020, when the first wave has faded out. The analysis focuses on the significance of four sociodemographic variables: socioeconomic status, population density, rate of elderly population and minority status (Jewish / Arab identity) of the population in cities with 5000 residents or more. Additionally, we take a closer look into the association between morbidity rates and one SES component – home Internet access.

Methods

The article is a cross sectional study of morbidity rates, investigated on a residential community basis. Following the descriptive statistics, we move on to present multivariate analysis to explore associations between these variables and Covid-19 morbidity in Israel.

Results

Both the descriptive statistics and regressions show morbidity rates to be positively associated with population density. Socioeconomic status as well as the size of elderly population were both significantly related to morbidity, but only in Jewish communities. Interestingly, the association was inverse in both cases. i.e., the higher the SES the lower the morbidity and the larger the elderly population, the lower the community’s morbidity. Another interesting result is that overall, morbidity rates in Jewish cities were consistently higher than in Arab communities.

Conclusions

We attribute the low morbidity rates in communities with relatively small elderly populations to the exceptionally high fertility rates in ultra-orthodox communities that sustained increased rates of morbidity; the lower morbidity in Arab communities is attributed to several factors, including the spatial Jewish-Arab segregation.
Chitosan-miRNA functionalized microporous titanium oxide surfaces via a layer-by-layer approach with a sustained release profile for enhanced osteogenic activity
Authors: Wu Kaimin , Liu Mengyuan , Li Nan , Zhang Li , Meng Fanhui , Zhao Lingzhou , Liu Min , Zhang Yumei
Published: September 2020

Background

The biofunctionalization of titanium implants for high osteogenic ability is a promising approach for the development of advanced implants to promote osseointegration, especially in compromised bone conditions. In this study, polyelectrolyte multilayers (PEMs) were fabricated using the layer-by-layer approach with a chitosan-miRNA (CS-miRNA) complex and sodium hyaluronate (HA) as the positively and negatively charged polyelectrolytes on microarc-oxidized (MAO) Ti surfaces via silane-glutaraldehyde coupling.

Methods

Dynamic contact angle and scanning electron microscopy measurements were conducted to monitor the layer accumulation. RiboGreen was used to quantify the miRNA loading and release profile in phosphate-buffered saline. The in vitro transfection efficiency and the cytotoxicity were investigated after seeding mesenchymal stem cells (MSCs) on the CS-antimiR-138/HA PEM-functionalized microporous Ti surface. The in vitro osteogenic differentiation of the MSCs and the in vivo osseointegration were also evaluated.

Results

The surface wettability alternately changed during the formation of PEMs. The CS-miRNA nanoparticles were distributed evenly across the MAO surface. The miRNA loading increased with increasing bilayer number. More importantly, a sustained miRNA release was obtained over a timeframe of approximately 2 weeks. In vitro transfection revealed that the CS-antimiR-138 nanoparticles were taken up efficiently by the cells and caused significant knockdown of miR-138 without showing significant cytotoxicity. The CS-antimiR-138/HA PEM surface enhanced the osteogenic differentiation of MSCs in terms of enhanced alkaline phosphatase, collagen production and extracellular matrix mineralization. Substantially enhanced in vivo osseointegration was observed in the rat model.

Conclusions

The findings demonstrated that the novel CS-antimiR-138/HA PEM-functionalized microporous Ti implant exhibited sustained release of CS-antimiR-138, and notably enhanced the in vitro osteogenic differentiation of MSCs and in vivo osseointegration. This novel miRNA-functionalized Ti implant may be used in the clinical setting to allow for more effective and robust osseointegration.
Impact of pre-transplant dialysis modality on the outcome and health-related quality of life of patients after simultaneous pancreas-kidney transplantation
Authors: Scheuermann Uwe , Rademacher Sebastian , Jahn Nora , Sucher Elisabeth , Seehofer Daniel , Sucher Robert , Hau Hans-Michael
Published: September 2020

Background

Simultaneous pancreas-kidney transplantation (SPKT) profoundly improves the health-related quality of life (HRQoL) of recipients. However, the influence of the pre-transplant dialysis modality on the success of the SPKT and post-transplant HRQoL remains unknown.

Methods

We analyzed the surgical outcome, long-term survival, as well as HRQoL of 83 SPKTs that were performed in our hospital between 2000 and 2016. Prior to transplant, 64 patients received hemodialysis (HD) and nineteen patients received peritoneal dialysis (PD). Physical and mental quality of life results from eight basic scales and the physical and mental component summaries (PCS and MCS) were measured using the Short Form 36 (SF-36) survey.

Results

Peri- and postoperative complications, as well as patient and graft survival were similar between the two groups. Both groups showed an improvement of HRQoL in all SF-36 domains after transplantation. Compared with patients who received HD before transplantation, PD patients showed significantly better results in four of the eight SF-36 domains: physical functioning (mean difference HD - PD: − 12.4 ± 4.9, P = < 0.01), bodily pain (− 14.2 ± 6.3, P < 0.01), general health (− 6.3 ± 2.8, P = 0.04), vitality (− 6.8 ± 2.6, P = 0.04), and PCS (− 5.2 ± 1.5, P < 0.01) after SPKT. In the overall study population, graft loss was associated with significant worsening of the HRQoL in all physical components (each P < 0.01).

Conclusions

The results of this analysis show that pre-transplant dialysis modality has no influence on the outcome and survival rate after SPKT. Regarding HRQoL, patients receiving PD prior to SPKT seem to have a slight advantage compared with patients with HD before transplantation.
Modeling the Cost-effectiveness of Esophageal Cancer Screening in China
Authors: Li Yuanyuan , Du Lingbin , Wang Youqing , Gu Yuxuan , Zhen Xuemei , Hu Xiaoqian , Sun Xueshan , Dong Hengjin
Published: September 2020

Background

This study aimed to examine the cost-effectiveness of one-time standard endoscopic screening with Lugol’s iodine staining for esophageal cancer (EC) in China.

Methods

A Markov decision analysis model with eleven states was built. Individuals aged 40 to 69 years were classified into six age groups in five-year intervals. Three different strategies were adopted for each cohort: (1) no screening; (2) one-time endoscopic screening with Lugol’s iodine staining with an annual follow-up for low-grade intraepithelial neoplasia (LGIN); and (3) one-time endoscopic screening with Lugol’s iodine staining without follow-up. Quality-adjusted life-years (QALYs) indicated the effectiveness of the model. The incremental cost-effectiveness ratio (ICER) was used as the evaluation indicator. Sensitivity analysis was performed to assess the robustness of the model.

Results

One-time screening with follow-up was the undominated strategy for individuals aged 40–44 and 45–49 years, which saved USD 10,942.57 and USD 6611.73 per QALY gained compared to nonscreening strategy. For those aged 50–69 years, the nonscreening scenarios were undominated. One-time screening without follow-up was the extended dominated strategy. Compared to screening strategies without follow-up, all the screening strategies with follow-up were more cost-effective, with the ICER increasing from 299.57 USD/QALY for individuals aged 40–44 years to 1617.72 USD/QALY for individuals aged 65–69 years. Probabilistic sensitivity analysis (PSA) supported the results of the base case analysis.

Conclusions

One-time EC screening with follow-up targeting individuals aged 40–49 years was the most cost-effective strategy.
Juvenile Spondyloarthritis: focus on uveitis
Authors: Marino Achille , Weiss Pamela F. , Brandon Timothy G. , Lerman Melissa A.
Published: September 2020

Background

Juvenile spondyloarthritis (JSpA) represents a group of inflammatory arthritides with several distinctive features (enthesitis, involvement of spine and sacroiliac joint, HLA-B27 association and development of uveitis). There are limited data on the course of uveitis in children with JSpA.

This study aims to estimate the prevalence of uveitis and to look at the presence of HLA-B27 in relation to uveitis occurrence and ocular symptoms in a cohort of JSpA patients.

Findings

This is a cross sectional/retrospective study involving patients with JSpA followed in a tertiary referral hospital.

Two hundred twenty-three patients were enrolled in the study. The prevalent diagnosis was enthesitis-related arthritis (ERA) (62%) followed by juvenile psoriatic arthritis (PsA), undifferentiated arthritis (UA), and the arthropathies associated with inflammatory bowel disease (IBD-A) (18, 14, 6%, respectively).

Uveitis was reported in twenty-four patients (11%) of the JSpA cohort (JSpA-U). ERA patients had the highest uveitis prevalence (ERA-U) (13%) with similar prevalences in UA, PsA and in IBD-A (7% each).

The prevalence of HLA-B27 positivity was similar amongst the entire JSpA-U cohort (N = 22, 45%) and those with ERA-U (N = 8, 44%). The overall prevalence of symptomatic uveitis was 79%. Neither the likelihood of uveitis, nor of symptomatic uveitis, varied by HLA-B27 status either in the entire cohort nor in those with ERA.

Conclusions

About one-tenth of patients developed uveitis, the majority of which was symptomatic. Fewer than half of the patients with uveitis were HLA-B27 positive. HLA-B27 status was not statistically associated with either the development of uveitis or symptomaticity of uveitis.
A novel positive feedback-loop between the HTLV-1 oncoprotein Tax and NF-κB activity in T-cells
Authors: Millen Sebastian , Meretuk Lina , Göttlicher Tim , Schmitt Sarah , Fleckenstein Bernhard , Thoma-Kress Andrea K.
Published: September 2020

Background

Human T-cell leukemia virus type 1 (HTLV-1) infects primarily CD4+T-lymphocytes and evoques severe diseases, predominantly Adult T-Cell Leukemia/ Lymphoma (ATL/L) and HTLV-1-associated Myelopathy/ Tropical Spastic Paraparesis (HAM/TSP). The viral transactivator of the pX region (Tax) is important for initiating malignant transformation, and deregulation of the major signaling pathway nuclear factor of kappa B (NF-κB) by Tax represents a hallmark of HTLV-1 driven cancer.

Results

Here we found that Tax mutants which are defective in NF-κB signaling showed diminished protein expression levels compared to Tax wildtype in T-cells, whereasTaxtranscript levels were comparable. Strikingly, constant activation of NF-κB signaling by the constitutive active mutant ofinhibitor of kappa B kinase(IKK2, IKK-β), IKK2-EE, rescued protein expression of the NF-κB defective Tax mutants M22 and K1-10R and even increased protein levels of Tax wildtype in various T-cell lines whileTaxtranscript levels were only slightly affected. Using several Tax expression constructs, an increase of Tax protein occurred independent ofTaxtranscripts and independent of the promoter used. Further, Tax and M22 protein expression were strongly enhanced by 12-O-Tetradecanoylphorbol-13-Acetate [TPA; Phorbol 12-myristate 13-acetate (PMA)]/ ionomycin, inducers of NF-κB and cytokine signaling, but not by tumor necrosis factor alpha (TNF-α). On the other hand, co-expression of Tax with a dominant negative inhibitor of κB, IκBα-DN, or specific inhibition of IKK2 by the compound ACHP, led to a vast decrease in Tax protein levels to some extent independent ofTaxtranscripts in transiently transfected and Tax-transformed T-cells. Cycloheximide chase experiments revealed that co-expression of IKK2-EE prolongs the half-life of M22, and constant repression of NF-κB signaling by IκBα-DN strongly reduces protein stability of Tax wildtype suggesting that NF-κB activity is required for Tax protein stability. Finally, protein expression of Tax and M22 could be recovered by NH4Cl and PYR-41, inhibitors of the lysosome and the ubiquitin-activating enzyme E1, respectively.

Conclusions

Together, these findings suggest that Tax’s capability to induce NF-κB is critical for protein expression and stabilization of Tax itself. Overall, identification of this novel positive feedback loop between Tax and NF-κB in T-cells improves our understanding of Tax-driven transformation.
Human MDSCs derived from the bone marrow maintain their functional ability but have a reduced frequency of induction in the elderly compared to pediatric donors
Authors: Magri Sara , Masetto Elena , Solito Samantha , Francescato Samuela , Belluzzi Elisa , Pozzuoli Assunta , Berizzi Antonio , Ruggieri Pietro , Mandruzzato Susanna
Published: September 2020

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immunosuppressive cells developing from myeloid progenitors, which are enriched in pathological conditions such as cancer, and are known to inhibit the functions of effector T cells. During aging, several changes occur both at the adaptive and innate immune system level, in a process defined as immunoscenescence. In particular, the low-grade inflammation state observed in the elderly appears to affect hematopoiesis. We previously demonstrated that the combination of GM-CSF and G-CSF drives the in vitro generation of bone marrow-derived MDSCs (BM-MDSCs) from precursors present in human bone marrow aspirates of healthy donors, and that these cells are endowed with a strong immune suppressive ability, resembling that of cancer-associated MDSCs. In the present work we investigated BM-MDSCs induction and functional ability in a cohort of pediatric versus elderly donors. To this aim, we analyzed the differences in maturation stages and ability to suppress T cell proliferation. We found that the ex vivo distribution of myeloid progenitors is similar between pediatric and elderly individuals, whereas after cytokine treatment a significant reduction in the more immature compartment is observed in the elderly. Despite the decreased frequency, BM-MDSCs maintain their suppressive capacity in aged donors. Taken together, these results indicate that in vitro induction of MDSCs from the BM is reduced with aging and opens new hypotheses on the role of age-related processes in myelopoiesis.
Level of knowledge, acceptability, and willingness to use oral fluid HIV self-testing among medical students in Kilimanjaro region, Tanzania: a descriptive cross-sectional study
Authors: Vara Proches Arobogast , Buhulula Luyeye Sostenes , Mohammed Fatma Aziz , Njau Bernard
Published: September 2020

Background

HIV Self-Testing (HIVST) is universally accepted as an innovative strategy complimenting existing HIV testing services to archive the UNAIDS, 95-95-95 goals by 2030. However, the adoption of HIVST is lagging in most sub-Saharan countries, including Tanzania. This study aimed to determine the level of knowledge, acceptability, and willingness to use HIVST among Medical students in Kilimanjaro region, Tanzania.

Methods

A descriptive cross-sectional study using a self-administered, semi-structured questionnaire was conducted from May to June 2019 among 271 medical students aged 18–44 years enrolled in a degree of Medicine course at Kilimanjaro Christian Medical University College.

Results

A total of 271 participants were enrolled (response rate of 100%). The mean age was 23.9 (SD 2.9), the majority (91%) were Christians, being single (92%), and a half (50.2%) were males. More than half (55.7%) was sexually active, 67.5% reported the age of first sexual debut at 19 years and above. The majority (81.5%) reported that they had one sexual partner, 37% used condoms during the last sexual act. The majority (98.7%) had never had a sexually transmitted disease during the past 3 months, 22.5% reported using alcohol when having sex. More than three-quarters (79%) ever tested for HIV, and 41.6% tested for HIV in the past year. More than two-thirds (67.9%) had a high level of knowledge on oral fluid HIV self-test. Being a female was related with high level of knowledge (P = 0.225). The acceptability of HIVST was 62.7%, and about two-thirds showed a willingness to buy a self-test kit if available for public use.

Conclusions

The high level of knowledge on oral fluid HIV self-testing, acceptability and willingness to buy self-test kit if available for public use among sexually active medical students underscores the importance of introducing HIVST as a complementary approach for existing HIV testing services in this setting. To make HIVST effective, interventionist should address concerns associated with self-testing, such as lack of pre and post-test counseling, suicidal risks after receiving HIV positive results, perceived risks of inaccurate HIVST test results, lack of linkage to care of individuals receiving HIV positive results, perceived risks of intimate partner violence, coercive testing of a female partner, and perceived high cost of buying self-test kits.
Chemically defined human vascular laminins for biologically relevant culture of hiPSC-derived brain microvascular endothelial cells
Authors: Motallebnejad Pedram , Azarin Samira M.
Published: September 2020

Background

In recent years, differentiation of human induced pluripotent stem cells (hiPSCs) into brain-specific microvascular endothelial cells (iBMECs) has frequently been used to model the blood–brain barrier (BBB). However, there are limitations in the use of iBMECs for in vitro studies, such as transendothelial electrical resistance (TEER) instability, weak junctional expression of VE-cadherin, and lack of proper fluid shear stress response. In vivo, the basement membrane (BM) composition of the BBB evolves throughout development, and laminins become the dominant component of the mature vascular BM. However, laminin isoforms of the endothelial BM have not been used for culture of differentiated iBMECs. The main goal of this study is to investigate the effect of different laminin isoforms of the endothelial BM on iBMEC functionality and to determine whether better recapitulation of the physiological BM in vitro can address the aforementioned limitations of iBMECs.

Methods

Using a previously reported method, hiPSCs were differentiated into iBMECs. The influence of main laminins of the endothelial BM, LN 411 and LN 511, on iBMEC functionality was studied and compared to a collagen IV and fibronectin mixture (CN IV-FN). Quantitative RT-PCR, immunocytochemistry, and TEER measurement were utilized to assess gene and protein expression and barrier properties of iBMECs on different extracellular matrices. Single-channel microfluidic devices were used to study the effect of shear stress on iBMECs.

Results

LN 511, but not LN 411, improved iBMEC barrier properties and resulted in more sustained TEER stability. Immunocytochemistry showed improved junctional protein expression compared to iBMECs cultured on CN IV-FN. iBMECs cultured on LN 511 showed a reduction of stress fibers, indicating resting endothelial phenotype, whereas gene expression analysis revealed upregulation of multiple genes involved in endothelial activation in iBMECs on CN IV-FN. Finally, culturing iBMECs on LN 511 enhanced physiological responses to shear stress, including morphological changes and enhanced junctional protein association.

Conclusion

LN 511 improves the functionality and long-term barrier stability of iBMECs. Our findings suggest that incorporation of physiologically relevant LN 511 in iBMEC culture would be beneficial for disease modeling applications and BBB-on-a-chip platforms that accommodate fluid flow.
The anxious aspects of insecure attachment styles are associated with depression either in pregnancy or in the postpartum period
Authors: Bianciardi Emanuela , Vito Cristina , Betrò Sophia , De Stefano Alberto , Siracusano Alberto , Niolu Cinzia
Published: September 2020

Background

Perinatal depression (PND) is a major complication of pregnancy and many risk factors have been associated with its development both during pregnancy and postpartum. The transition to motherhood activates the attachment system. The aim of our study was to investigate the relationship between women’s attachment style (AS) and PND in pregnancy, and 1 month after childbirth, in a large cohort of women. We hypothesized that different patterns of AS were associated with either antenatal or postnatal depression. We, further, explored the role of other possible risk factors such as life-stress events.

Methods

A final sample of 572 women was enrolled. At the third trimester of pregnancy, clinical data sheet and self-report questionnaires (ASQ, PSS, LTE-Q, and EPDS) were administered. One month after delivery, EPDS was administered by telephone interview.

Results

We found 10.1% of the women with depression during pregnancy and 11.1% in the postpartum period. The first logistic regression showed that ASQ-CONF subscale (OR = 0.876, p < 0.0001), ASQ-NFA subscale (OR = 1.097, p = 0.002), foreign nationality (OR = 2.29, p = 0.040), low education levels (OR = 0.185, p = 0.012), PSS total score (OR = 1.376, p = 0.010), and recent life adversities (OR = 3.250, p = 0.012) were related to EPDS ≥ 14 during pregnancy.

The second logistic regression showed that ASQ-PRE subscale (OR = 1.077, p < 0.001) and foreign nationality (OR = 2.88, p = 0.010) were related to EPDS ≥ 12 in the postpartum period.

Conclusions

Different dimensions of anxious insecure AS were, respectively, associated with either antenatal or postnatal depression. These findings support the literature investigating subtypes of perinatal depression. The PND may be heterogeneous in nature, and the comprehension of psychopathological trajectories may improve screening, prevention, and treatment of a disorder which has a long-lasting disabling impact on the mental health of mother and child. We provided a rationale for targeting an attachment-based intervention in this group of women.
Prohibited, but still present: local and traditional knowledge about the practice and impact of forest grazing by domestic livestock in Hungary
Authors: Varga Anna , Demeter László , Ulicsni Viktor , Öllerer Kinga , Biró Marianna , Babai Dániel , Molnár Zsolt
Published: September 2020

Background

Forests have been grazed for millennia. Around the world, forest grazing by livestock became a controversial management practice, gradually restricted in many countries over the past 250 years. This was also the case in most Central and Eastern European countries, including Hungary, where forest grazing was a legally prohibited activity between 1961 and 2017. Until the 2010s, ecologists and nature conservationists considered it merely as a historical form of forest use. As a result, there is little contemporary scientific information available about the impact of forest grazing on vegetation and the traditional ecological knowledge associated with it. Our aim was to explore and summarize this type of knowledge held by herders in Hungary.

Methods

We interviewed 58 knowledgeable herders and participated in forest grazing activities in 43 study locations across the country. The results were analysed qualitatively.

Results

We revealed a living ecological knowledge tradition and practice of forest grazing in native and non-native forest stands. The impact of livestock grazing on native and non-native forests is not considerably different, in the view of the herders. For both forest types, the greatest impact of grazing was the suppression of the shrub layer, while grazing also increased the dominance and palatability (“tameness”) of the grasses. Livestock could cause significant damage to seedlings during forest grazing, but if done with care, grazing could also be an integral part of forestry management.

Conclusions

Sustainability of current forest grazing practices depends on the depth of local and traditional knowledge applied and herders’ stewardship. We stress the importance of collaborating with holders of local and traditional knowledge in order to gain a better understanding of the effects of livestock grazing on vegetation in temperate forests.