bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucose and lipid lowering effects of Enhydra fluctuans extract in cadmium treated normal and type-2 diabetic model rats
Authors: Hasan Mohammad Nazmul , Sabrin Farah , Rokeya Begum , Khan Md Shahinul Haque , Ahmed Mahtab Uddin , Matondo Abel , Billah Md Morsaline , Akter Salima 
Published: October 2019

AbstractBackgroundRecent epidemiological and experimental studies suggest that cadmium and diabetes-related hyperglycemia may act synergistically to worsen metabolic regulation. The present study aims to evaluate the potential effects ofEnhydra fluctuansextract in diabetes and dyslipidemia in cadmium (CdCl2) induced- normal and type 2 diabetic model rats.MethodForty-eight Long-Evans rats were divided equally into the following six groups: Normal Control (N-C), Normal treated with CdCl2(N-Cd), Normal treated with plant extract (N-P), Normal treated with both plant extract and CdCl2(N-PCd), Diabetic treated with plant extract (DM-P) and Diabetic treated with both plant extract and CdCl2 (DM-PCd). Blood glucose and other biochemical parameters were estimated by the enzymatic colorimetric method. Histological analysis of liver and heart was done by the hematoxylin-eosin (H & E) method.ResultsTwenty-one days treatment ofE. fluctuansextracts at a dose of 200 mg/kg significantly reduced blood glucose level in N-PCd and DM-PCd (p < 0.05), and DM-P (p < 0.01) group. The plant extract had no direct effects on total blood lipids but, it had beneficial effects on TG/HDL-C ratio in N-P and DM-PCd groups (p < 0.05). Cd induction significantly reduced body weight [(N-Cd, N-PCd, DM-PCd) (p < 0.01)], and induced liver [N-Cd (p < 0.05), N-PCd,p < 0.001] and renal impairment [N-Cd (p < 0.05)]. In bi-variate association, a significant positive correlation between serum glucose and SGPT (p < 0.05) as well as SGPT and TG/HDL ratio (p = 0.019) was found in DM-P and in the merged group. The histology of liver and heart showed severe damages including inflammation, nuclear pyknosis, loss of myocardial fibers, necrosis and fibrosis in the Cd treated groups compared to plant treated groups.ConclusionE. fluctuansseems to have potent antihyperglycemic effects in diabetes and Cd toxicity along with partial antidyslipidemic properties in euglycemic and diabetic rats. Our study suggests a novel oral antihyperglycemic agent in the present environmental context.
Are there decision support tools that might strengthen the health system for perinatal care in South African district hospitals? A review of the literature
Authors: Nkwanyana Ntombifikile Maureen , Voce Anna Silvia 
Published: October 2019

Abstract

Background
South Africa has a high burden of perinatal deaths in spite of the availability of evidence-based interventions. The majority of preventable perinatal deaths occur in district hospitals and are mainly related to the functioning of the health system. Particularly, leadership in district hospitals needs to be strengthened in order to decrease the burden of perinatal mortality. Decision-making is a key function of leaders, however leaders in district hospitals are not supported to make evidence-based decisions. The aim of this research was to identify health system decision support tools that can be applied at district hospital level to strengthen decision-making in the health system for perinatal care in South Africa.

Methods
A structured approach, the systematic quantitative literature review method, was conducted to find published articles that reported on decision support tools to strengthen decision-making in a health system for perinatal, maternal, neonatal and child health. Articles published in English between 2003 and 2017 were sought through the following search engines: Google Scholar, EBSCOhost and Science Direct. Furthermore, the electronic databases searched were: Academic Search Complete, Health Source – Consumer Edition, Health Source – Nursing/Academic Edition and MEDLINE.

Results
The search yielded 6366 articles of which 43 met the inclusion criteria for review. Four decision support tools identified in the articles that met the inclusion criteria were the Lives Saved Tool, Maternal and Neonatal Directed Assessment of Technology model, OneHealth Tool, and Discrete Event Simulation. The analysis reflected that none of the identified decision support tools could be adopted at district hospital level to strengthen decision-making in the health system for perinatal care in South Africa.

Conclusion
There is a need to either adapt an existing decision support tool or to develop a tool that will support decision-making at district hospital level towards strengthening the health system for perinatal care in South Africa.
Life satisfaction in Norwegian medical doctors: a 15-year longitudinal study of work-related predictors
Authors: Mahmood Javed Iqbal , Grotmol Kjersti Støen , Tesli Martin , Moum Torbjørn , Andreassen Ole , Tyssen Reidar 
Published: October 2019

AbstractBackgroundDespite many recent studies on burn-out and dissatisfaction among American medical doctors, less is known about doctors in the Scandinavian public health service. The aims of this study were to analyse long-term work-related predictors of life satisfaction among established doctors in Norway and to identify predictors in a subgroup of doctors who reported a decline in life satisfaction.MethodsTwo nationwide cohorts of doctors (n = 1052), who graduated medical school 6 years apart, were surveyed at graduation from medical school (T1, 1993/94 and 1999), and 4 (T2), 10 (T3), and 15 (T4) years later. Work-related predictors of life satisfaction (three items) obtained at T2 to T4 were analysed. Individual and lifestyle confounders were controlled for using mixed-models repeated-measures analyses, and logistic regression analyses were applied to identify predictors of the decrease in life satisfaction.ResultsNinety per cent (947/1052) responded at least once, and 42% (450/1052) responded at all four times. Work-related predictors of higher life satisfaction in the adjusted model were work–home stress (β = − 0.20, 95% confidence interval [CI] = − 0.25 to − 0.16,p < 0.001), perceived job demands (β = − 0.10, CI = − 0.15 to − 0.05,p < 0.001), and colleague support (β = 0.05, CI = 0.04 to 0.07,p < 0.001). The new adjusted individual predictors that we identified included female gender, reality weakness trait, and problematic drinking behaviour. Neuroticism trait and low colleague support predicted a decrease in life satisfaction.ConclusionsWork–home stress, perceived job demands, and colleague support were the most important predictors of life satisfaction related to doctors’ work. When personality traits were controlled for, female doctors were more satisfied with their life than male doctors. These findings suggest that improving work-related factors with targeted interventions, including a supportive work environment, may increase life satisfaction among doctors.
Development and validation of a novel MR imaging predictor of response to induction chemotherapy in locoregionally advanced nasopharyngeal cancer: a randomized controlled trial substudy (NCT01245959)
Authors: Dong Di , Zhang Fan , Zhong Lian-Zhen , Fang Meng-Jie , Huang Cheng-Long , Yao Ji-Jin , Sun Ying , Tian Jie , Ma Jun , Tang Ling-Long 
Published: October 2019

AbstractBackgroundIn locoregionally advanced nasopharyngeal carcinoma (LANPC) patients, variance of tumor response to induction chemotherapy (ICT) was observed. We developed and validated a novel imaging biomarker to predict which patients will benefit most from additional ICT compared with chemoradiotherapy (CCRT) alone.MethodsAll patients, including retrospective training (n = 254) and prospective randomized controlled validation cohorts (a substudy of NCT01245959,n = 248), received ICT+CCRT or CCRT alone. Primary endpoint was failure-free survival (FFS). From the multi-parameter magnetic resonance images of the primary tumor at baseline, 819 quantitative 2D imaging features were extracted. Selected key features (according to their interaction effect between the two treatments) were combined into an Induction Chemotherapy Outcome Score (ICTOS) with a multivariable Cox proportional hazards model using modified covariate method. Kaplan-Meier curves and significance test for treatment interaction were used to evaluate ICTOS, in both cohorts.ResultsThree imaging features were selected and combined into ICTOS to predict treatment outcome for additional ICT. In the matched training cohort, patients with a high ICTOS had higher 3-year and 5-year FFS in ICT+CCRT than CCRT subgroup (69.3% vs. 45.6% for 3-year FFS, and 64.0% vs. 36.5% for 5-year FFS; HR = 0.43, 95% CI = 0.25–0.74,p = 0.002), whereas patients with a low ICTOS had no significant difference in FFS between the subgroups (p = 0.063), with a significant treatment interaction (pinteraction <  0.001). This trend was also found in the validation cohort with high (n = 73, ICT+CCRT 89.7% and 89.7% vs. CCRT 61.8% and 52.8% at 3-year and 5-year; HR = 0.17, 95% CI = 0.06–0.51,p <  0.001) and low ICTOS (n = 175,p = 0.31), with a significant treatment interaction (pinteraction = 0.019). Compared with 12.5% and 16.6% absolute benefit in the validation cohort (3-year FFS from 69.9 to 82.4% and 5-year FFS from 63.4 to 80.0% from additional ICT), high ICTOS group in this cohort had 27.9% and 36.9% absolute benefit. Furthermore, no significant survival improvement was found from additional ICT in both groups after stratifying low ICTOS patients into low-risk and high-risks groups, by clinical risk factors.ConclusionAn imaging biomarker, ICTOS, as proposed, identified patients who were more likely to gain additional survival benefit from ICT+CCRT (high ICTOS), which could influence clinical decisions, such as the indication for ICT treatment.Trial registrationClinicalTrials.gov,NCT01245959. Registered 23 November 2010.
Paving the way for more precise diagnosis of EcPV2-associated equine penile lesions
Authors: Ramsauer Anna Sophie , Wachoski-Dark Garrett Louis , Fraefel Cornel , Tobler Kurt , Brandt Sabine , Knight Cameron Greig , Favrot Claude , Grest Paula 
Published: October 2019

Abstract

Background
There is growing evidence that equine papillomavirus type 2 (EcPV2) infection is causally associated with the development of equine genital squamous cell carcinomas (SCCs). Early stages of disease present clinically as plaques or wart-like lesions which can gradually progress to tumoural lesions. Histologically these lesions are inconsistently described as benign hyperplasia, papilloma, penile intraepithelial neoplasia (PIN), carcinoma in situ (CIS) or SCC. Guidelines for histological classification of early SCC precursor lesions are not precisely defined, leading to potential misdiagnosis. The aim of this study was to identify histologic criteria and diagnostic markers allowing for a more accurate diagnosis of EcPV2-associated equine penile lesions.

Results
A total of 61 archived equine penile lesions were histologically re-assessed and classified as benign hyperplasia, papilloma, CIS or SCC. From these, 19 representative lesions and adjacent normal skin were comparatively analysed for the presence of EcPV2 DNA and transcripts using PCR and RNA in situ hybridisation (RISH). All lesional samples were positive by EcPV2 PCR and RISH, while adjacent normal skin was negative. RISH analysis yielded signal distribution patterns that allowed distinction of early (hyperplasia, papilloma) from late stage lesions (CIS, SCC). Subsequently, the 19 lesions were further assessed for expression of p53, Ki67, MCM7 and MMP1 by immunohistochemistry (IHC). All four proteins were expressed in both normal and lesional tissue. However, p53 expression was up-regulated in basal keratinocyte layers of papillomas, CIS and SCCs, as well as in upper keratinocyte layers of CIS and SCCs. MCM7 expression was only up-regulated in upper proliferating keratinocyte layers of papillomas, CIS and SCCs.

Conclusion
This study proposes combining a refined histological protocol for analysis of equine penile lesions with PCR- and/or RISH based EcPV2-screening and p53/MCM7 IHC to more accurately determine the type of lesion. This may help to guide the choice of optimum treatment strategy, especially at early stages of disease.
Characterization of five newly derived canine osteosarcoma cell lines
Authors: Wilson-Robles Heather , Franks Kelli , Pool Roy , Miller Tasha 
Published: October 2019

Abstract

Background
Canine and human osteosarcomas (OS) are notably similar and have a high rate of metastasis. There is a poor understanding of the tumor development process, predisposing causes, and varying levels of aggression among different cell lines. By characterizing newly developed canine osteosarcoma cell lines, treatments for people and pets can be developed. Of the seven subtypes of OS, three are represented in this group: osteoblastic (the most common), fibroblastic, and giant cell variant. To our knowledge, there are no other giant cell variant canine OS cell lines in the published literature and only one canine fibroblastic osteosarcoma cell line. Understanding the differences between the histologic subtypes in dogs will help to guide comparative research.

Results
Alkaline phosphatase expression was ubiquitous in all cell lines tested and invasiveness was variable between the cell lines tested. Invasiveness and oxidative damage were not correlated with in vivo growth rates, where TOT grew the fastest and had the higher percentage of mice with metastatic lesions. TOL was determined to be the most chemo-resistant during cisplatin chemotherapy while TOM was the most chemo-sensitive.

Conclusions
Further comparisons and studies using these cell lines may identify a variety of characteristics valuable for understanding the disease process and developing treatments for osteosarcoma in both species.
Some of this data was presented as a poster by KMF at the August 5th, 2017 National Veterinary Scholars Program in Bethesda, MA.
Characterization of 5 newly generated canine osteosarcoma cell lines.
Kelli Franks, Tasha Miller, Heather Wilson-Robles.
Role of XIAP gene overexpressed bone marrow mesenchymal stem cells in the treatment of cerebral injury in rats with cerebral palsy
Authors: Deng Wenjing , Fan Chenghe , Fang Yanbo , Zhao Yanan , Wei Yamin , Li Meng , Teng Junfang 
Published: October 2019

Abstract

Background
This study is performed to investigate the effects of adenovirus-mediated X-linked inhibitor of apoptosis protein (XIAP) overexpressed bone marrow mesenchymal stem cells (BMSCs) on brain injury in rats with cerebral palsy (CP).

Methods
Rat’s BMSCs were cultured and identified. The XIAP gene of BMSCs was modified by adenovirus expression vector Ad-XIAP-GFP. The rat model of CP with ischemia and anoxia was established by ligating the left common carotid artery and anoxia for 2 h, and BMSCs were intracerebroventricularly injected to the modeled rats. The mRNA and protein expression of XIAP in brain tissue of rats in each group was detected by RT-qPCR and western blot analysis. The neurobehavioral situation, content of acetylcholine (Ach), activity of acetylcholinesterase (AchE), brain pathological injury, apoptosis of brain nerve cells and the activation of astrocytes in CP rats were determined via a series of assays.

Results
Rats with CP exhibited obvious abnormalities, increased Ach content, decreased AchE activity, obvious pathological damage, increased brain nerve cell apoptosis, as well as elevated activation of astrocyte. XIAP overexpressed BMSCs improved the neurobehavioral situation, decreased Ach content and increased AchE activity, attenuated brain pathological injury, inhibited apoptosis of brain nerve cells and the activation of astrocytes in CP rats.

Conclusion
Our study demonstrates that XIAP overexpressed BMSCs can inhibit the apoptosis of brain nerve cells and the activation of astrocytes, increase AchE activity, and inhibit Ach content, so as to lower the CP caused by cerebral ischemia and hypoxia in rats.
The role of exosomal PD-L1 in tumor progression and immunotherapy
Authors: Xie Feiting , Xu Mengxue , Lu Jian , Mao Lingxiang , Wang Shengjun 
Published: October 2019

Abstract
Programmed death ligand 1 (PD-L1), a type I transmembrane protein, binds to its receptor PD-1 to suppress the activation of T cells, thereby maintaining immunological homeostasis. In contrast, tumor cells highly express PD-L1, which binds to receptor PD-1 expressed on activated T cells, leading to immune escape. Anti-PD-1/PD-L1 immune checkpoint therapy blocks the binding of PD-1/PD-L1 to reinvigorate the exhausted T cells, thereby inhibiting tumor growth. Exosomes are biologically active lipid-bilayer nanovesicles secreted by various cell types that mediate intercellular signal communication. Numerous studies have shown that tumor cells are able to promote tumor epithelial-mesenchymal transition, angiogenesis, and immune escape by releasing exosomes. Recent studies imply that tumor-derived exosomes could carry PD-L1 in the same membrane topology as the cell surface, thereby resisting immune checkpoint therapy. In this review, we mainly discuss the role of exosomes in the regulation of tumor progression and the potential resistance mechanism to immunotherapy via exosomal PD-L1. In addition, we propose that exosomal PD-L1 may have the potential to be a target to overcome resistance to anti-PD-1/PD-L1 antibody therapy.
Differential placental ceramide levels during gestational diabetes mellitus (GDM)
Authors: Mejia Juan F. , Hirschi Kelsey M. , Tsai Kary Y. F. , Long Matthew G. , Tullis Benton C. , Bitter Eliza E. K. , Bikman Benjamin T. , Reynolds Paul R. , Arroyo Juan A. 
Published: October 2019

Abstract

Background
Gestational diabetes mellitus (GDM) is associated with important factors that influence fetal development. Sphingolipids are known to be associated with the development of diabetes. Our objective was to examine ceramide, a key sphingolipid, hyperosmolarity, and apoptosis in placentas from GDM patients treated with insulin or diet.

Methods
Ceramide levels were assessed in placental tissues using immunohistochemistry. Immunoblot was performed to quantify serine palmitoyltransferase (SPT), the rate-limiting enzyme in ceramide biosynthesis, NFAT5, SMIT, AR, caspase 3 and the X-linked inhibitor of apoptosis. Trophoblast cells were treated with insulin or ceramide and assessments for mitochondrial respiration, caspase 3 and XIAP were also performed.

Results
Immunohistochemistry showed increased ceramides in the placental villous trophoblasts of the insulin-treated GDM patients. Nuclear SPT was upregulated only in the insulin-treated GDM placenta when compared to controls. Nuclear NFAT5 was also increased in the GDM placenta. Active caspase 3 was elevated in placentas from both insulin- and diet-treated GDM patients. Mitochondrial respiration was decreased in trophoblasts treated with ceramide. Active caspase was not changed while XIAP protein was increased in trophoblasts treated with ceramide.

Conclusions
Our findings confirm the presence of ceramide in the human placenta of control and GDM patients. Furthermore, we conclude that ceramide is increased in the placental trophoblast during insulin treatment and that its upregulation correlates with elevated NFAT5, SMIT, increased apoptosis and decreased trophoblast mitochondrial respiration.
Tibial post fracture pain is reduced in kinin receptors deficient mice and blunted by kinin receptor antagonists
Authors: Minville Vincent , Mouledous Lionel , Jaafar Acil , Couture Réjean , Brouchet Anne , Frances Bernard , Tack Ivan , Girolami Jean-Pierre 
Published: October 2019

AbstractBackgroundTibial fracture is associated with inflammatory reaction leading to severe pain syndrome. Bradykinin receptor activation is involved in inflammatory reactions, but has never been investigated in fracture pain.MethodsThis study aims at defining the role of B1 and B2-kinin receptors (B1R and B2R) in a closed tibial fracture pain model by using knockout mice for B1R (B1KO) or B2R (B2KO) and wild-type (WT) mice treated with antagonists for B1R (SSR 240612 and R954) and B2R (HOE140) or vehicle. A cyclooxygenase (COX) inhibitor (ketoprofen) and an antagonist (SB366791) of Transient Receptor Potential Vaniloid1 (TRPV1) were also investigated since these pathways are associated with BK-induced pain in other models. The impact on mechanical and thermal hyperalgesia and locomotion was assessed by behavior tests. Gene expression of B1R and B2R and spinal cord expression of c-Fos were measured by RT-PCR and immunohistochemistry, respectively.ResultsB1KO and B2KO mice demonstrated a reduction in post-fracture pain sensitivity compared to WT mice that was associated with decreased c-Fos expression in the ipsilateral spinal dorsal horn in B2KO. B1R and B2R mRNA and protein levels were markedly enhanced at the fracture site. B1R and B2R antagonists and inhibition of COX and TRPV1 pathways reduced pain in WT. However, the analgesic effect of the COX-1/COX-2 inhibitor disappeared in B1KO and B2KO. In contrast, the analgesic effect of the TRPV1 antagonist persisted after gene deletion of either receptor.ConclusionsIt is suggested that B1R and B2R activation contributes significantly to tibial fracture pain through COX. Hence, B1R and B2R antagonists appear potential therapeutic agents to manage post fracture pain.
The impact on anatomical landmark identification after an ultrasound-guided palpation intervention: a pilot study
Authors: Cho John Chinsuk , Reckelhoff Kenneth 
Published: October 2019

Abstract

Background
To determine whether a discrepancy exists in identifying three musculoskeletal landmarks (medial meniscus, lateral malleolus and lateral epicondyle of the humerus) and whether ultrasound-guided (US-guided) palpation intervention can reduce that discrepancy and improve localization for chiropractic interns.

Methods
Sixteen chiropractic interns were asked to identify three subcutaneous anatomical landmarks before/ after the intervention and at a 3-day follow-up. The intervention was a three-minute US-guided demonstration of the landmarks after the intern’s initial localization. The primary outcome measure was the change in distance between the intern’s landmark identification. Non-normal data were analyzed with the Friedman’s and Wilcoxon signed rank tests. Discrepancy between examiner-determined landmarks and intern-identified landmarks at the initial time point was assessed with a 1-sample Wilcoxon signed rank test.

Results
All locations demonstrated an initial discrepancy between examiner-determined landmarks and intern-identified landmarks at the initial time point. Overall, a statistically significant difference was noted in the identification of the medial meniscus (p = 0.012) and lateral malleolus (p = 0.001), but not at the lateral epicondyle (p = 0.086). For the before and immediately after comparison, a significant improvement was found with the medial meniscus (p = 0.005) and lateral malleolus (p = 0.002). The 3-day post-intervention comparison found an improvement only for the lateral malleolus (p = 0.008).

Conclusion
This pilot study demonstrated palpatory discrepancy at identifying all three landmarks. Our data suggests that US-guided palpation intervention seems to improve an intern’s ability to palpate two landmarks (medial meniscus and lateral malleolus) post-intervention.