bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway
Authors: Yang Ye , Liu Ping Yin , Bao Wei , Chen Song Jun , Wu Fang Su , Zhu Ping Ya
Published: January 2020

Background

Pyroptosis belongs to a novel inflammatory programmed cell death pathway, with the possible prognosis of endometrial cancer related to the terminal protein GSDMD. Hydrogen exerts a biphasic effect on cancer by promoting tumor cell death and protecting normal cells, which might initiate GSDMD pathway-mediated pyroptosis.

Methods

We performed immunohistochemical staining and western immunoblotting analysis to observe expression of NLRP3, caspase-1, and GSDMD in human and xenograft mice endometrial cancer tissue and cell lines. We investigated treatment with hydrogen could boost ROS accumulation in endometrial cancer cells by intracellular and mitochondrial sources. GSDMD shRNA lentivirus was used to transfect endometrial cancer cells to investigate the function of GSDMD protein in pyroptosis. Propidium iodide (PI) staining, TUNEL assay, measurement of lactate dehydrogenase (LDH) release and IL-1β ELISA were used to analysis pyroptosis between hydrogen-supplemented or normal culture medium. We conducted in vivo human endometrial tumor xenograft mice model to observe anti-tumor effect in hydrogen supplementation.

Results

We observed overexpression of NLRP3, caspase-1, and GSDMD in human endometrial cancer and cell lines by IHC and western immunoblotting. Hydrogen pretreatment upregulated ROS and the expression of pyroptosis-related proteins, and increased the number of PI- and TUNEL-positive cells, as well as the release of LDH and IL-1β, however, GSDMD depletion reduced their release. We further demonstrated that hydrogen supplementation in mice was sufficient for the anti-tumor effect to inhibit xenograft volume and weight of endometrial tumors, as mice subjected to hydrogen-rich water displayed decreased radiance. Tumor tissue sections in the HRW groups presented moderate-to-strong positive expression of NLRP3, caspase-1 and GSDMD. Hydrogen attenuated tumor volume and weight in a xenograft mouse model though the pyroptotic pathway.

Conclusions

This study extended our original analysis of the ability of hydrogen to stimulate NLRP3 inflammasome/GSDMD activation in pyroptosis and revealed possible mechanism (s) for improvement of anti-tumor effects in the clinical management of endometrial cancer.
Mortality after hospital admission for heart failure: improvement over time, equally strong in women as in men
Authors:   on behalf of the Queen of Hearts and RECONNECT investigators, Buddeke J. , Valstar G. B. , van Dis I. , Visseren F. L. J. , Rutten F. H. , den Ruijter H. M. , Vaartjes I. , Bots M. L.
Published: January 2020

Background

To assess the trend in age- and sex-stratified mortality after hospitalization for heart failure (HF) in the Netherlands.

Methods

Two nationwide cohorts of patients, hospitalized for new onset heart failure between 01.01.2000–31.12.2002 and between 01.01.2008–31.12.2010, were constructed by linkage of the Dutch Hospital Discharge Registry and the National Cause of Death registry. 30-day, 1-year and 5 -year overall and cause-specific mortality rates stratified by age and sex were assessed and compared over time.

Results

We identified 40,230 men and 41,582 women. In both cohorts, men were on average younger than women (74–75 and 78–79 years, respectively) and more often had comorbid conditions (37 and 30%, respectively). In the 2008–10 cohort, mortality rates for men were 13, 32 and 64% for respectively 30-day, 1-year and 5-year mortality and 14, 33 and 66% for women. Mortality rates increased considerably with age similarly in men and women (e.g. from 10.5% in women aged 25–54 to 46.1% in those aged 85 and older after 1 year). Between the two time periods, mortality rates dropped across all ages, equally strong in women as in men. The 1-year absolute risk of death declined by 4.0% (from 36.1 to 32.1%) in men and 3.2% (from 36.2 to 33.0%) in women.

Conclusions

Mortality after hospitalization for new onset HF remains high, however, both short-term and long-term survival is improving over time. This improvement was similar across all ages and equally strong in women as in men.
Refusals to perform ritual circumcision: a qualitative study of doctors’ professional and ethical reasoning
Authors: Litleskare Liv Astrid , Strander Mette Tolås , Førde Reidun , Magelssen Morten
Published: January 2020

Background

Ritual circumcision of infant boys is controversial in Norway, as in many other countries. The procedure became a part of Norwegian public health services in 2015. A new law opened for conscientious objection to the procedure. We have studied physicians’ refusals to perform ritual circumcision as an issue of professional ethics.

Method

Qualitative interview study with 10 urologists who refused to perform ritual circumcision from six Norwegian public hospitals. Interviews were recorded and transcribed, then analysed with systematic text condensation, a qualitative analysis framework.

Results

The physicians are unanimous in grounding their opposition to the procedure in professional standards and norms, based on fundamental tenets of professional ethics. While there is homogeneity in the group when it comes to this reasoning, there are significant variations as to how deeply the matter touches the urologists on a personal level. About half of them connect their stance to their personal integrity, and state that performing the procedure would go against their conscience and lead to pangs of conscience.

Conclusions

It is argued that professional moral norms sometimes might become more or less ‘integrated’ in the professional’s core moral values and moral identity. If this is the case, then the distinction between conscience-based and professional refusals to certain healthcare services cannot be drawn as sharply as it has been.
Improving emergency obstetric referral systems in low and middle income countries: a qualitative study in a tertiary health facility in Ghana
Authors: Daniels Anita Anima , Abuosi Aaron
Published: January 2020

Background

Timely access to emergency obstetric care is crucial in preventing mortalities associated with pregnancy and childbirth. The referral of patients from lower levels of care to higher levels has been identified as an integral component of the health care delivery system in Ghana. To this effect, in 2012, the National Referral Policy and Guidelines was developed by the Ministry of Health (MOH) to help improve standard procedures and reduce delays which affect access to emergency care. Nonetheless, ensuring timely access to care during referral of obstetric emergencies has been problematic. The study aimed to identify barriers associated with the referral of emergency obstetric cases to the leading national referral centre. It specifically examines the lived experiences of patients, healthcare providers and relatives of patients on the referral system.

Methods

Korle Bu Teaching Hospital, Accra was used as a case study in 2016.The qualitative method was used and in-depth interviews were conducted with 89 respondents: healthcare providers [n = 34];patients [n = 31] and relatives of patients [n = 24] using semi-structured interview guides. Purposive sampling techniques were used in selecting healthcare providers and patients and convenience sampling techniques were used in selecting relatives of patients.

Results

The study identified a range of barriers encountered in the referral process and broadly fall under the major themes: referral transportation system, referrer-receiver communication barriers, inadequate infrastructure and supplies and insufficient health personnel. Some highlights of the problem included inadequate use of ambulance services, poor management of patients during transit, lack of professional escort, unannounced emergency referrals, lack of adequate information and feedback and limited supply of beds, drugs and blood. These findings have implications on type II and III of the three delays model.

Conclusions

Initiatives to improve the transportation system for the referral of obstetric emergencies are vital in ensuring patients’ safety during transfer. Communication between referring and receiving facilities should be enhanced. A strong collaboration is needed between teaching hospitals and other stakeholders in the referral chain to foster good referral practices and healthcare delivery. Concurrently, supply side barriers at referred facilities including ensuring sufficient provision for bed, blood, drugs, and personnel must be addressed.
Clinical isolates of Tritrichomonas foetus in bulls in Wyoming, South Dakota and Montana, USA
Authors: Jin Yinzhu , Du Aifang , Yao Chaoqun
Published: January 2020

Background

Several Tritrichomonas species have been found in mammalian hosts. Among these trichomonads T. foetus is often found in the urogenital tract of cattle and the gastrointestinal tract of the domestic cat, resulting in sexually transmitted bovine trichomonosis and fecal-orally transmitted feline trichomonosis, respectively. The aims of the current study were to molecularly characterize clinical isolates of T. foetus in cattle populations in Wyoming, South Dakota, and Montana of the United States of America and to phylogenetically analyze Tritrichomonas species of mammalian hosts.

Results

DNA sequencing of rRNA genes showed over 99% identity of the newly described isolates to other bovine isolates. Further, T. foetus isolates of various mammalian hosts originated in different geographic regions worldwide were clustered into two well-defined clades by phylogenetic analysis of rRNA and cysteine protease 2 genes. Clade I consisted of isolates originated from cattle, pig, and human whereas clade II contained isolates of cat and dog.

Conclusion

It is concluded that all mammalian Tritrichomonas spp. apparently belong to T. foetus. Analysis of more sequences is warranted to support this conclusion.
Construction of asthma related competing endogenous RNA network revealed novel long non-coding RNAs and potential new drugs
Authors: Liao Yifang , Li Ping , Wang Yanxia , Chen Hong , Ning Shangwei , Su Dongju
Published: January 2020

Background

Asthma is a heterogeneous disease characterized by chronic airway inflammation. Long non-coding RNA can act as competing endogenous RNA to mRNA, and play significant role in many diseases. However, there is little known about the profiles of long non-coding RNA and the long non-coding RNA related competing endogenous RNA network in asthma. In current study, we aimed to explore the long non-coding RNA-microRNA-mRNA competing endogenous RNA network in asthma and their potential implications for therapy and prognosis.

Methods

Asthma-related gene expression profiles were downloaded from the Gene Expression Omnibus database, re-annotated with these genes and identified for asthma-associated differentially expressed mRNAs and long non-coding RNAs. The long non-coding RNA-miRNA interaction data and mRNA-miRNA interaction data were downloaded using the starBase database to construct a long non-coding RNA-miRNA-mRNA global competing endogenous RNA network and extract asthma-related differentially expressed competing endogenous RNA network. Finally, functional enrichment analysis and drug repositioning of asthma-associated differentially expressed competing endogenous RNA networks were performed to further identify key long non-coding RNAs and potential therapeutics associated with asthma.

Results

This study constructed an asthma-associated competing endogenous RNA network, determined 5 key long non-coding RNAs (MALAT1, MIR17HG, CASC2, MAGI2-AS3, DAPK1-IT1) and identified 8 potential new drugs (Tamoxifen, Ruxolitinib, Tretinoin, Quercetin, Dasatinib, Levocarnitine, Niflumic Acid, Glyburide).

Conclusions

The results suggested that long non-coding RNA played an important role in asthma, and these novel long non-coding RNAs could be potential therapeutic target and prognostic biomarkers. At the same time, potential new drugs for asthma treatment have been discovered through drug repositioning techniques, providing a new direction for the treatment of asthma.
The stability of blood Eosinophils in chronic obstructive pulmonary disease
Authors: Long Gabriella H. , Southworth Thomas , Kolsum Umme , Donaldson Gavin C. , Wedzicha Jadwiga A. , Brightling Christopher E. , Singh Dave
Published: January 2020

Blood eosinophils are a predictive biomarker of inhaled corticosteroid response in chronic obstructive pulmonary disease (COPD). We investigated blood eosinophil stability over 1 year using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019 thresholds of < 100, 100- < 300 and ≥ 300 eosinophils/μL in 225 patients from the COPDMAP cohort. Blood eosinophils showed good stability (rho: 0.71, p < 0.001, ICC 0.84), and 69.3% of patients remained in the same eosinophil category at 1 year. 85.3% of patients with eosinophils < 100 cells/μL had stable counts. The majority of blood eosinophil counts remain stable over 1 year using the GOLD 2019 thresholds.
Silencing of miR-17-5p suppresses cell proliferation and promotes cell apoptosis by directly targeting PIK3R1 in laryngeal squamous cell carcinoma
Authors: Wang Jian-Xing , Jia Xin-Ju , Liu Yan , Dong Jin-Hui , Ren Xiu-Min , Xu Ou , Liu Sheng-Hui , Shan Chun-Guang
Published: January 2020

Background

Increasing evidence has suggested that microRNAs (miRNAs) act as key post-transcriptional regulators in tumor progression. Previous studies have confirmed that miR-17-5p functions as an oncogene in multiple cancers and contributes to tumor progression. However, the role and biological functions of miR-17-5p in the development of laryngeal squamous cell carcinoma (LSCC) still remain unknown.

Methods

qRT-PCR was used to detect miRNA and mRNA expression levels in LSCC tissues and cell lines. CCK-8 assay was used to measure cell viability and flow cytometry was performed to evaluate cell apoptosis. Western blot analysis was used to detect the protein levels of BAX, BCL-2, cleaved Caspase-3, PIK3R1 and AKT. Luciferase reporter assay was used to detect the effect of miR-17-5p on PIK3R1 expression. Xenograft animal model was used to test the effect of miR-17-5p on LSCC cell in vivo.

Results

In the present study, we found that miR-17-5p expression level was upregulated in LSCC tissues and cell lines. Depletion of miR-17-5p in LSCC cells significantly reduced cell proliferation and promoted cell apoptosis in vitro and in vivo. Mechanically, knockdown of miR-17-5p in LSCC cells inhibited BCL-2 expression while enhanced BAX and cleaved Caspase-3 protein expression. Moreover, depletion of miR-17-5p in LSCC cells suppressed AKT phosphorylation but did not influence PTEN expression. Importantly, miR-17-5p positively regulated PIK3R1 expression by directly binding to its 3′-untranslated region (UTR). Additionally, PIK3R1, which expression was downregulated in LSCC tissues and cell lines, was involved in LSCC cell survival by modulating the activation of AKT signal pathway. Dysregulation of miR-17-5p/PIK3R1 axis was participated in LSCC cell proliferation and apoptosis by inhibiting the activation of the PI3K/AKT signaling pathway.

Conclusions

In conclusion, our study indicates that the miR-17-5p/PIK3R1 axis plays an essential role in the development of LSCC and provides a potential therapeutic target for LSCC treatment.
Delayed frozen embryo transfer failed to improve live birth rate and neonatal outcomes in patients requiring whole embryo freezing
Authors: He Yuxia , Zheng Haiyan , Du Hongzi , Liu Jianqiao , Li Lei , Liu Haiying , Cao Mingzhu , Chen Shiping
Published: January 2020

Background

Controlled ovarian stimulation (COS) has a negative effect on the endometrial receptivity compared with natural menstrual cycle. Whether it’s necessary to postpone the first frozen embryo transfer (FET) following a freeze-all strategy in order to avoid any residual effect on endometrial receptivity consequent to COS was inconclusive.

Objective

The purpose of this retrospective study was to explore whether the delayed FET improve the live birth rate and neonatal outcomes stratified by COS protocols after a freeze-all strategy.

Methods

A total of 4404 patients who underwent the first FET cycle were enrolled in this study between April 2014 to December 2017, and were divided into immediate (within the first menstrual cycle following withdrawal bleeding) or delayed FET (waiting for at least one menstrual cycle and the transferred embryos were cryopreserved for less than 6 months). Furthermore, each group was further divided into two subgroups according to COS protocols, and the pregnancy and neonatal outcomes were analyzed between the immediate and delayed FET following the same COS protocol.

Results

When FET cycles following the same COS protocol, there was no significant difference regarding the rates of live birth, implantation, clinical pregnancy, multiple pregnancy, early miscarriage, premature birth and stillbirth between immediate and delayed FET groups. Similarly, no significant differences were found for the mean gestational age, the mean birth weight, and rates of low birth weight and very low birth weight between the immediate and delayed FET groups. The sex ratio (male/female) and the congenital anomalies rate also did not differ significantly between the two FET groups stratified by COS protocols.

Conclusion

Regardless of COS protocols, FET could be performed immediately after a freeze-all strategy for delaying FET failed to improve reproductive and neonatal outcomes.
The potential therapeutic effects of the gut microbiome manipulation by synbiotic containing-Lactobacillus plantarum on neuropsychological performance of diabetic rats
Authors: Morshedi Mohammad , Saghafi-Asl Maryam , Hosseinifard Elaheh-Sadat
Published: January 2020

Background

The manipulation of gut microbiota as a target has been suggested to reduce the risks for a number of diseases such as type 2 diabetes mellitus (T2DM). Conversely, T2DM is associated with complications such as gut and brain disorders. Furthermore, the impact of probiotics and prebiotics to improve T2DM complications are reported. Thus, the present study seeks to investigate the therapeutic and neuropsychological effects of L. plantarum and inulin in diabetic rats.

Methods

Throughout the investigation, L. plantarum, inulin or their combination (synbiotic) was administered to diabetic rats. in the end, fecal samples were collected to evaluate the gut microbial composition. Then behavioral tests were conducted. Subsequently, the obtainment of the prefrontal cortex (PFC) and hippocampal samples.

Results

Our data demonstrated that administration of L. plantarum and inulin could improve gut dysbiosis and oxidative stress status. In addition, it could ameliorate serotonin and BDNF/TrkB signaling pathway. Notably, a strong correlation between the gut microbiota changes and cognition responses was observed. Interestingly, synbiotics intake exploited a rather powerful effect on oxidative stress markers.

Conclusion

The findings confirm that there is a beneficial therapeutic potential of supplements, especially symbiotic. Moreover, neuropsychological improvement associated with balanced gut microbiome.
Transcriptome analysis defines myocardium gene signatures in children with ToF and ASD and reveals disease-specific molecular reprogramming in response to surgery with cardiopulmonary bypass
Authors: Raggi Federica , Cangelosi Davide , Becherini Pamela , Blengio Fabiola , Morini Martina , Acquaviva Massimo , Belli Maria Luisa , Panizzon Giuseppe , Cervo Giuseppe , Varesio Luigi , Eva Alessandra , Bosco Maria Carla
Published: January 2020

Background

Tetralogy of Fallot (ToF) and Atrial Septal Defects (ASD) are the most common types of congenital heart diseases and a major cause of childhood morbidity and mortality. Cardiopulmonary bypass (CPB) is used during corrective cardiac surgery to support circulation and heart stabilization. However, this procedure triggers systemic inflammatory and stress response and consequent increased risk of postoperative complications. The aim of this study was to define the molecular bases of ToF and ASD pathogenesis and response to CPB and identify new potential biomarkers.

Methods

Comparative transcriptome analysis of right atrium specimens collected from 10 ToF and 10 ASD patients was conducted before (Pre-CPB) and after (Post-CPB) corrective surgery. Total RNA isolated from each sample was individually hybridized on Affymetrix HG-U133 Plus Array Strips containing 38,500 unique human genes. Differences in the gene expression profiles and functional enrichment/network analyses were assessed using bioinformatic tools. qRT-PCR analysis was used to validate gene modulation.

Results

Pre-CPB samples showed significant differential expression of a total of 72 genes, 28 of which were overexpressed in ToF and 44 in ASD. According to Gene Ontology annotation, the mostly enriched biological processes were represented by matrix organization and cell adhesion in ToF and by muscle development and contractility in ASD specimens. GSEA highlighted the specific enrichment of hypoxia gene sets in ToF samples, pointing to a role for hypoxia in disease pathogenesis. The post-CPB myocardium exhibited significant alterations in the expression profile of genes related to transcription regulation, growth/apoptosis, inflammation, adhesion/matrix organization, and oxidative stress. Among them, only 70 were common to the two disease groups, whereas 110 and 24 were unique in ToF and ASD, respectively. Multiple functional interactions among differentially expressed gene products were predicted by network analysis. Interestingly, gene expression changes in ASD samples followed a consensus hypoxia profile.

Conclusion

Our results provide a comprehensive view of gene reprogramming in right atrium tissues of ToF and ASD patients before and after CPB, defining specific molecular pathways underlying disease pathophysiology and myocardium response to CPB. These findings have potential translational value because they identify new candidate prognostic markers and targets for tailored cardioprotective post-surgical therapies.
Budget impact analysis of robotic exoskeleton use for locomotor training following spinal cord injury in four SCI Model Systems
Authors: Pinto Daniel , Garnier Mauricio , Barbas Jason , Chang Shuo-Hsiu , Charlifue Susan , Field-Fote Edelle , Furbish Catherine , Tefertiller Candy , Mummidisetty Chaithanya K. , Taylor Heather , Jayaraman Arun , Heinemann Allen W.
Published: January 2020

Background

We know little about the budget impact of integrating robotic exoskeleton over-ground training into therapy services for locomotor training. The purpose of this study was to estimate the budget impact of adding robotic exoskeleton over-ground training to existing locomotor training strategies in the rehabilitation of people with spinal cord injury.

Methods

A Budget Impact Analysis (BIA) was conducted using data provided by four Spinal Cord Injury (SCI) Model Systems rehabilitation hospitals. Hospitals provided estimates of therapy utilization and costs about people with spinal cord injury who participated in locomotor training in the calendar year 2017. Interventions were standard of care walking training including body-weight supported treadmill training, overground training, stationary robotic systems (i.e., treadmill-based robotic gait orthoses), and overground robotic exoskeleton training. The main outcome measures included device costs, training costs for personnel to use the device, human capital costs of locomotor training, device demand, and the number of training sessions per person with SCI.

Results

Robotic exoskeletons for over-ground training decreased hospital costs associated with delivering locomotor training in the base case analysis. This analysis assumed no difference in intervention effectiveness across locomotor training strategies. Providing robotic exoskeleton overground training for 10% of locomotor training sessions over the course of the year (range 226–397 sessions) results in decreased annual locomotor training costs (i.e., net savings) between $1114 to $4784 per annum. The base case shows small savings that are sensitive to parameters of the BIA model which were tested in one-way sensitivity analyses, scenarios analyses, and probability sensitivity analyses. The base case scenario was more sensitive to clinical utilization parameters (e.g., how often devices sit idle and the substitution of high cost training) than device-specific parameters (e.g., robotic exoskeleton device cost or device life). Probabilistic sensitivity analysis simultaneously considered human capital cost, device cost, and locomotor device substitution. With probabilistic sensitivity analysis, the introduction of a robotic exoskeleton only remained cost saving for one facility.

Conclusions

Providing robotic exoskeleton for over-ground training was associated with lower costs for the locomotor training of people with SCI in the base case analyses. The analysis was sensitive to parameter assumptions.
Early fulminant BK polyomavirus-associated nephropathy in two kidney transplant patients with low neutralizing antibody titers receiving allografts from the same donor
Authors: Lorentzen Elias Myrvoll , Henriksen Stian , Kaur Amandeep , Kro Grete Birkeland , Hammarström Clara , Hirsch Hans H. , Midtvedt Karsten , Rinaldo Christine Hanssen
Published: January 2020

Background

BK Polyomavirus (BKPyV) causes premature graft failure in 1 to 15% of kidney transplant (KT) recipients. High-level BKPyV-viruria and BKPyV-DNAemia precede polyomavirus-associated nephropathy (PyVAN), and guide clinical management decisions. In most cases, BKPyV appears to come from the donor kidney, but data from biopsy-proven PyVAN cases are lacking. Here, we report the early fulminant course of biopsy-proven PyVAN in two male KT recipients in their sixties, receiving kidneys from the same deceased male donor.

Case presentations

Both recipients received intravenous basiliximab induction, and maintenance therapy consisting of tacrolimus (trough levels 3–7 ng/mL from time of engraftment), mycophenolate mofetil 750 mg bid, and prednisolone. At 4 weeks post-transplant, renal function was satisfactory with serum creatinine concentrations of 106 and 72 μmol/L in recipient #1 and recipient #2, respectively. Plasma BKPyV-DNAemia was first investigated at 5 and 8 weeks post-transplant being 8.58 × 104and 1.12 × 106copies/mL in recipient #1 and recipient #2, respectively. Renal function declined and biopsy-proven PyVAN was diagnosed in both recipients at 12 weeks post-transplant. Mycophenolate mofetil levels were reduced from 750 mg to 250 mg bid while tacrolimus levels were kept below 5 ng/mL. Recipient #2 cleared BKPyV-DNAemia at 5.5 months post-transplant, while recipient #1 had persistent BKPyV-DNAemia of 1.07 × 105copies/mL at the last follow-up 52 weeks post-transplant. DNA sequencing of viral DNA from early plasma samples revealed apparently identical viruses in both recipients, belonging to genotype Ib-2 with archetype non-coding control region. Retrospective serological work-up, demonstrated that the donor had high BKPyV-IgG-virus-like particle ELISA activity and a high BKPyV-genotype I neutralizing antibody titer, whereas both KT recipients only had low neutralizing antibody titers pre-transplantation. By 20 weeks post-transplant, the neutralizing antibody titer had increased by > 1000-fold in both recipients, but only recipient #2 cleared BKPyV-DNAemia.

Conclusions

Low titers of genotype-specific neutralizing antibodies in recipients pre-transplant, may identify patients at high risk for early fulminant donor-derived BKPyV-DNAemia and PyVAN, but development of high neutralizing antibody titers may not be sufficient for clearance.
Inhalation of welding fumes reduced sperm counts and high fat diet reduced testosterone levels; differential effects in Sprague Dawley and Brown Norway rats
Authors: Skovmand Astrid , Erdely Aaron , Antonini James M. , Nurkiewicz Timothy R. , Shoeb Mohammad , Eye Tracy , Kodali Vamsi , Loeschner Katrin , Vidmar Janja , Agerholm Jørgen S. , Goericke-Pesch Sandra , Vogel Ulla , Hougaard Karin S.
Published: January 2020

Background

Previous studies have shown that inhalation of welding fumes may induce pulmonary and systemic inflammation and organ accumulation of metal, to which spermatogenesis and endocrine function may be sensitive. Also obesity may induce low-grade systemic inflammation. This study aimed to investigate the effects on sperm production of inhaled metal nanoparticles from stainless steel welding, and the potential exacerbation by intake of a high fat diet. Both the inbred Brown Norway and the outbred Sprague Dawley rat strains were included to study the influence of strain on the detection of toxicity. Rats were fed regular or high fat (HF) diet for 24 weeks and were exposed to 20 mg/m3of gas metal arc-stainless steel (GMA-SS) welding fumes or filtered air for 3 h/day, 4 days/week for 5 weeks, during weeks 7–12. Outcomes were assessed upon termination of exposure (week 12) and after recovery (week 24).

Results

At week 12, the GMA-SS exposure induced pulmonary inflammation in both strains, without consistent changes in markers of systemic inflammation (CRP, MCP-1, IL-6 and TNFα). GMA-SS exposure lowered daily sperm production compared to air controls in Sprague Dawley rats, but only in GMA-SS Brown Norway rats also fed the HF diet. Overall, HF diet rats had lower serum testosterone levels compared to rats on regular diet. Metal content in the testes was assessed in a limited number of samples in Brown Norway rats, but no increase was obsedrved. At week 24, bronchoalveolar lavage cell counts had returned to background levels for GMA-SS exposed Sprague Dawley rats but remained elevated in Brown Norway rats. GMA-SS did not affect daily sperm production statistically significantly at this time point, but testicular weights were lowered in GMA-SS Sprague Dawley rats. Serum testosterone remained lowered in Sprague Dawley rats fed the HF diet.

Conclusion

Exposure to GMA-SS welding fumes lowered sperm production in two strains of rats, whereas high fat diet lowered serum testosterone. The effect on sperm counts was likely not mediated by inflammation or lowered testosterone levels. The studied reproductive outcomes seemed more prone to disruption in the Sprague Dawley compared to the Brown Norway strain.
Debranching thoracic endovascular aortic repair for distal aortic arch aneurysm in elderly patients aged over 75 years old
Authors: Shiraya Suguru , Nakamura Yoshinobu , Harada Shingo , Kishimoto Yuichiro , Onohara Takeshi , Otsuki Yuki , Kurashiki Tomohiro , Horie Hiromu , Nishimura Motonobu
Published: January 2020

Background

We examined the outcome of debranching thoracic endovascular aortic repair (d-TEVAR) without sternotomy for distal aortic arch aneurysm in patients aged ≥75 years.

Methods

Patients who underwent d-TEVAR or TAR for aortic arch aneurysm between 2008 and 2015 at our hospital and aged ≥75 years were included. Age, sex, left ventricular ejection fraction, preoperative creatinine level, diabetes, cerebrovascular disease, and chronic obstructive pulmonary disease were matched using PS.

Results

Among 74 patients (d-TEVAR: 51, TAR: 23), 17 patients in each group were matched. No difference in surgical outcome was detected between the d-TEVAR and TAR groups, including 30-day death (0% vs. 0%), hospital death (5.8% vs. 0%: p = 0.31) and incidence of cerebral infarction (5.8% vs. 7.6%: p = 0.27) as well as the long-term outcomes of 5-year survival (92.8% vs. 74.8%: p = 0.30) and 5-year aorta-related event-free rate (88.2% vs. 100%: p = 0.15). Average duration of ICU stay (1.3 ± 1.1 days vs. 5.6 ± 1.3 days: p = 0.025) and hospital stay (16.5 ± 5.2 days vs. 37.7 ± 19.6 days: p = 0.017) were significantly shorter in the d-TEVAR group.

Conclusion

Our results indicated that d-TEVAR is less invasive without affecting long-term outcome up to 5 years. Although the number of the patients included in the study was small, debranching TEVAR could be one of the treatments of the choice in the elderly, especially with comorbidities.
A surgical case of mediastinal hematoma caused by a minor traffic injury
Authors: Suzuki Katsuyuki , Shiono Satoshi , Hayasaka Kazuki , Endoh Makoto
Published: January 2020

Background

Mediastinal hematoma rarely occurs after a minor traffic injury.

Case presentation

A woman in her forties was transferred to the emergency room by ambulance due to a traffic accident. Computed tomography (CT) revealed no abnormal findings, and she went home. Two days after the accident, the contrast-enhanced CT was repeated, which revealed cervical and mediastinal hematomas. Because it was possible that there was active bleeding from the right inferior thyroid artery, embolization of the right inferior thyroid artery was performed; however, her condition further deteriorated, so we performed emergency surgery to achieve hemostasis and remove the hematoma. Because of oozing from the right thyroid lobe, we performed right hemithyroidectomy and drainage of mediastinal space and right thoracic cavity. Since there was no bleeding site in the mediastinum, we thought that the mediastinal hematoma was due to bleeding from the thyroid gland. Her postoperative course was uneventful, and she is doing well at 9 months of follow-up after surgery.

Conclusions

It is possible that mediastinal hematoma might be caused by a minor traffic injury.
Protective effects of essential oil from Fructus Alpiniae zerumbet on retinal Müller gliosis via the PPAR-γ-p-CREB signaling pathway
Authors: Yang Hong , Gan Shiquan , Jiang Zhaohui , Song Xiaomei , Chen Tingting , Xu Yini , Fu Lingyun , Zhang Yanyan , Tao Ling , Shen Xiangchun
Published: January 2020

Background

Diabetic retinopathy (DR) involves extensive retinal damage and is one of the most common and serious complications of diabetes mellitus. Hyperglycemia is the major pathological trigger for diabetic complications. Müller cell gliosis, a key pathophysiological process in DR, could finally lead to vision loss. Our previous finding revealed that the essential oil of FructusAlpiniae zerumbet(EOFAZ) protects human umbilical vein endothelial cells (HUVECs) against high glucose (HG)-induced injury via the PPAR-γ signal. However, Whether EOFAZ could prevent HG-induced Müller cell gliosis through the PPAR signaling remains unclear.

Methods

The neuroprotective effects of EOFAZ were evaluated in HG-treated rat retinal Müller cells (RMCs) and DR rat model.

Result

GFAP and VEGF upregulation is the biomarker of Müller glial reactivity gliosis. Results suggested that EOFAZ could remarkably ameliorate retinal reactive gliosis by suppressing p-CREB and GFAP and VEGF downstream effectors. Its effects on PPAR-γ, a major target for currently available anti-diabetes drugs, were also investigated. EOFAZ treatment remarkably attenuated the reduction of PPAR-γ and high level of p-CaMK II and p-CREB in HG-treated RMCs and diabetic rats. Furthermore, the activation and ectopic expression of PPAR-γ downregulated p-CREB and p-CaMK II in HG-treated RMCs. By contrast, CaMK II inhibitor KN93 and CREB gene silencing did not significantly affect the PPAR-γ expression.

Conclusions

A novel PPAR-γ-p-CREB signaling pathway accounts for the inhibitory effect of EOFAZ on RMCs gliosis. These findings provide scientific evidence for the potential use of EOFAZ as a complementary and alternative medicine for DR prevention and treatment in the future.
Current shreds of evidence on the anticancer role of EGCG in triple negative breast cancer: an update of the current state of knowledge
Authors: Bimonte Sabrina , Cascella Marco , Barbieri Antonio , Arra Claudio , Cuomo Arturo
Published: January 2020

Triple-Negative Breast Cancer (TNBC), represents a subtype of breast cancer in which the estrogens receptor (ER) negative, the progesterone receptor (PR) negative and the human epidermal growth factor receptor 2 (HER2) negative, are not expressed. Thusly, TNBC does not respond to hormonal therapies or to those targeting the HER2 protein receptors. To overcome this flawed issue, new alternative therapies based on the use of natural substances, as the (−) - epigallocatechin 3-gallate (EGCG), has been proposed. It is largely documented that EGCG, the principal constituent of green tea, has suppressive effects on different types of cancer, including breast cancer, through the regulation of different signaling pathways. Thus, is reasonable to assume that EGCG could be viewed as a therapeutic option for the prevention and the treatment of TNBC. Here, we summarizing these promising results with the scope of turn a light on the potential roles of EGCG in the treatment of TNBC patients.
Cross-sectional and prospective study on anti-Müllerian hormone changes in a cohort of pre-menopausal women with a history of differentiated thyroid cancer
Authors: Mittica Miranda , Dotto Andrea , Comina Martina , Teliti Marsida , Monti Eleonora , Giusti Massimo
Published: January 2020

Background

Anti-Müllerian hormone (AMH) decreases acutely after post-surgical radioactive iodine (RAI) ablation in females with differentiated thyroid cancer (DTC).

Aim

We performed a cross-sectional and prospective study on AMH levels in pre-menopausal females with a history of DTC.

Methods

Fifty-nine females after surgery and RAI (group 1) and 30 females after surgery alone (group 2) were studied. The control group consisted of 141 healthy women (group 3). The prospective study was performed in 43 and 14 females from groups 1 and 2, respectively.

Results

On first evaluation, AMH levels were similar in groups 1 and 2, but lower than in group 3. In all groups, AMH was negatively related with chronological age and FSH levels. When subjects were stratified according to age, AMH levels were not different between groups. When AMH was evaluated up to 2 years after the baseline evaluation, no changes emerged in either group of women with DTC. In the prospective study, the incidence of abnormal menstrual cycles and the onset of menopause were observed in similar percentages of women with a history of RAI-treated DTC and of those treated with surgery alone.

Conclusions

AMH can be considered a reliable index of ovarian reserve in women with DTC. Chronological age is the main factor influencing AMH levels in both DTC patients and controls. After age-related stratification, AMH levels are similar in women with DTC treated with RAI and those treated with surgery alone.
A prospective, randomized, single-blind, multicentre, phase III study on organ preservation with Custodiol-N solution compared with Custodiol® solution in organ transplantation (kidney, liver and pancreas)
Authors: Kniepeiss Daniela , Houben Philipp , Stiegler Philipp , Berghold Andrea , Riedl Regina , Kahn Judith , Schemmer Peter
Published: January 2020

Background

Organ preservation before transplantation is still a challenge. Both the University of Wisconsin and Bretschneider’s histidine-tryptophan-ketoglutarate (HTK; Custodiol®) solution are standard for liver, kidney and pancreas preservation. Organ preservation with both solutions is comparable; recently, however, Custodiol® solution has been modified to Custodiol-N according to the needs of today. Thus, our study was defined to study its effect in clinical transplantation.

Methods

Patients undergoing kidney transplantation (n = 412) (including approximately 30 combined kidney–pancreas) or liver transplantation (n = 202) receive grafts that have been cold stored in either Custodiol® or Custodiol-N to demonstrate noninferiority of Custodiol-N regarding both graft function and graft injury after transplantation.

Discussion

Preclinical data have clearly shown that Custodiol-N is superior to Custodiol® in cold static organ preservation via mechanisms including inhibition of hypoxic cell injury, cold-induced cell injury and avoidance of adverse effects during warm exposure to the solution. Further clinical safety data on Custodiol-N for cardioplegia are available. Thus, this study was designed to compare Custodiol® with Custodiol-N for the first time in a prospective, randomized, single-blinded, multicentre, phase III clinical transplantation trial.

Trial registration

Eudra-CT, 2017–002198-20. Registered on 28 November 2018.
Implementing complaint-directed mini-interventions for depressive complaints in primary care to increase participation among patients with a lower socioeconomic status: design of a cluster randomised controlled trial
Authors: Leone Stephanie S. , Lokman Suzanne , Boon Brigitte , van der Poel Agnes , Smit Filip , Zijlstra-Vlasveld Moniek , Smeets Odile
Published: January 2020

Background

Depression is a major public health concern. E-health interventions for preventing and reducing depressive complaints have proven to be effective, and have the potential to make (mental) health care more accessible and efficient. However, the reach of these interventions needs to be improved, especially among people with a lower socioeconomic status (SES). Stimulating and supporting implementation of e-health in primary care, and offering guidance from general practice nurses (GP nurses) may be important strategies to achieve this.

Methods/design

The online ‘Complaint Directed Mini-Interventions’ (CDMIs) for stress, sleep and worry complaints, which were found to be (cost-)effective in a self-guided format, will be implemented in the primary care setting using a blended care format (i.e. combining e-health with face-to-face sessions) with minimal guidance provided by the GP nurse. The main aim is to evaluate whether a SES-sensitive implementation strategy improves the participation rate (i.e. reach) of lower-SES patients in the blended online CDMIs as compared to a regular implementation strategy in a cluster randomised controlled trial. Randomisation will occur at the level of the GP nurse, and 228 patients will be included in the study. The primary outcome is the participation rate (completing at least one face-to-face session and two online exercises) of the lower-SES target group. It is hypothesised that this percentage will be higher in the SES-sensitive group as compared to the regular group. Secondary objectives are to evaluate the implementation process, to monitor and evaluate psychological complaints (depression, sleep, stress, worry and anxiety) and well-being over time. Patient assessments will take place at baseline, 3 and 12 months post baseline.

Discussion

This study should contribute to our knowledge of reaching the lower-SES groups with a brief and complaint-specific blended approach for depressive complaints in primary care. It should also further our knowledge on successful strategies to implement depression prevention in primary care.

Trial registration

Netherlands Trial Register, ID: NL6595. Registered on 12 November 2017.
A systematic review of the efficiency of recruitment to stroke rehabilitation randomised controlled trials
Authors: McGill Kris , Sackley Catherine M. , Godwin Jon , McGarry Jodie , Brady Marian C.
Published: January 2020

Introduction

Randomised controlled trials (RCTs) that fail to meet their recruitment target risk increasing research waste. Acute stroke RCTs experience notable recruitment issues. The efficiency of recruitment to stroke rehabilitation RCTs has not been explored.

Aims and objectives

To explore recruitment efficiency and the trial features associated with efficient recruitment to stroke rehabilitation RCTs.

Methods

A systematic review of stroke rehabilitation RCTs published between 2005 and 2015 identified in a search of the Cochrane Stroke Group (CSG) Trials Register from 35 electronic databases (e.g. Medline, CINAHL; EMBASE), clinical trial registers, and hand-searching. Inclusion criteria are stroke rehabilitation intervention, delivered by a member of the rehabilitation team, and clinically relevant environment. We extracted data on recruitment efficiency and trial features.

Results

We screened 12,939 titles, 1270 abstracts and 788 full texts, before extracting data from 512 included RCTs (n = 28,804 stroke survivor participants). This is the largest systematic review of recruitment to date. A third of stroke survivors screened consented to participate (median 34% (IQR 14–61), on average sites recruited 1.5 participants per site per month (IQR 0.71–3.22), and one in twenty (6% (IQR 0–13) dropped out during the RCT. Almost half (48%) of those screened in the community were recruited compared to hospital settings (27%). Similarly, almost half (47%) those screened at least 6 months after stroke participated, compared to 23% of stroke survivors screened within a month of stroke. When one recruiter screened multiple sites, a median of one stroke survivor was recruited every 2 months compared to more than two per month when there was a dedicated recruiter per site. RCT recruitment was significantly faster per site, with fewer dropouts, for trials conducted in Asia (almost three stroke survivors monthly; 2% dropout) compared to European trials (approximately one stroke survivor monthly; 7% dropout).

Conclusions

One third of stroke survivors screened were randomised to rehabilitation RCTs at a rate of between one and two per month, per site. One in twenty did not complete the trial. Our findings will inform recruitment plans of future stroke rehabilitation RCTs. Limited reporting of recruitment details restricted the subgroup analysis performed.

Trial registration

Prospective Register of Systematic Reviews, registration number CRD42016033067.
Expanding our view of Bartonella and its hosts: Bartonella in nest ectoparasites and their migratory avian hosts
Authors: Williams Heather M. , Dittmar Katharina
Published: January 2020

Background

Bartonella is a genus of Gram-negative facultative intracellular Alphaproteobacteria of public health importance. Although they are known to mainly infect mammalian hosts with some blood-feeding arthropods having been confirmed as vectors, there is some evidence of Bartonella association with non-mammalian hosts including birds.

Methods

Here we used high-throughput sequencing of 16S rRNA and Sanger sequencing of the citrate synthase (gltA) genes to test for the presence of Bartonellaceae in the blood of three migratory cavity nesting bird species, purple martins (Progne subis), tree swallows (Tachycineta bicolor) and eastern bluebirds (Sialia sialis) and their most prevalent and abundant nest ectoparasites, Dermanyssus prognephilus (mite), Ceratophyllus idius (flea) and Protocalliphora sialia (bird blow fly larva). We constructed maximum likelihood phylogenetic trees to verify the placement of the resulting sequences in the Bartonellaceae.

Results

We found evidence of Bartonella in all three bird species and all three arthropod species tested. We report multiple instances of identical Bartonella sequences in both birds and parasites, leading to the likely hypothesis that these ectoparasites are potential vectors of Bartonella. Our phylogenetic analysis suggests that ‘avian Bartonella’ may form its own sub-clade within the genus Bartonella.

Conclusions

To the best of our knowledge, we provide the first confirmation of overlapping Bartonella strains among bird hosts and various species of nest-associated ectoparasites from the same system, suggesting a possible Bartonella host–vector relationship between these arthropods and a non-mammalian host. Our study adds to the growing appreciation of the Bartonellaceae as a phylogenetically diverse group with a wide range of hosts.