bluuebunny/crossref_metadata_2025_split huggingface dataset:
96-OR: Epigenetic Regulation of the TLR4 Pathway in Macrophages via S-adenosyl Methionine Results in Impaired Wound Healing in Diabetes
Authors: DAVIS FRANK M. , DENDEKKER AARON D. , KIMBALL ANDREW S. , BONIAKOWSKI ANNA , JOSHI AMRITA , ELAZZOUNY MAHMOUD , BURANT CHARLES , GALLAGHER KATHERINE 
Published: June 2019

Macrophage (Mφ) plasticity, allowing the transition of Mφs from an inflammatory to a reparative phenotype, is critical for normal wound healing. In pathologic conditions, such as type 2 diabetes (T2D), wounds fail to heal due to impaired resolution of Mφ inflammation. Although the mechanisms responsible for the persistent inflammatory phenotype in T2D wounds are unknown, recent investigations have revealed that cellular metabolites can alter Mφ function providing a link between metabolism and innate immunity. Further, there is increasing evidence that epigenetic mechanisms control Mφ function. The purpose of this study was to investigate if altered Mφ metabolism in T2D induces epigenetic modifications resulting in derangements in Mφ inflammation and impaired wound healing. Using the murine diet induce obesity (DIO) wound model, we demonstrate that diabetic bone marrow derived macrophages (BMDM) and wound Mφs display a hyperinflammatory phenotype following injury with increased expression of toll-like receptor (TLR) 4 signaling and proinflammatory cytokines (IL-1β and TNFα). Given that histone methylation has previously been shown by our group to influence Mφ phenotype, we examined H3K4 trimethylation on the TLR4 promoter and found a significant increase in DIO BMDMs and wound Mφs. To evaluate the impact of Mφ metabolites on inflammation we performed a LC-MS metabolite expression analysis demonstrating significant upregulation of the methyl donor, S-adenosyl methionine (SAM), which participates in histone methylation, and its rate limiting enzyme, MAT2a, in diabetic BMDMs.
In summary, these results suggest that increased levels of the metabolite SAM in diabetic Mφs contribute to an inflammatory Mφ phenotype via increased H3K4 methylation at the TLR4 promoter.

Disclosure
F.M. Davis: None. A.D. denDekker: None. A.S. Kimball: None. A. Boniakowski: None. A. Joshi: None. M. ElAzzouny: Employee; Self; Agilent Technologies. C. Burant: Stock/Shareholder; Self; Metabolic Solutions Development Company. K. Gallagher: None.

Funding
National Institutes of Health
Dapagliflozin Plus Saxagliptin Add-on Therapy Compared With Insulin in Patients With Type 2 Diabetes Poorly Controlled by Metformin With or Without Sulfonylurea Therapy: A Randomized Clinical Trial
Authors: Vilsbøll Tina , Ekholm Ella , Johnsson Eva , Dronamraju Nalina , Jabbour Serge , Lind Marcus 
Published: June 2019

OBJECTIVE
This study evaluated whether an oral combination of a sodium–glucose cotransporter 2 inhibitor and a dipeptidyl peptidase 4 inhibitor achieved glycemic control similar to basal insulin in patients with type 2 diabetes, poorly controlled with metformin, without increasing hypoglycemia or body weight.

RESEARCH DESIGN AND METHODS
In a multinational, open-label, randomized, phase 3 trial (ClinicalTrials.gov reg. no. NCT02551874), adults with type 2 diabetes inadequately controlled on metformin, with or without sulfonylurea, were randomized (1:1) to receive dapagliflozin (DAPA) plus saxagliptin (SAXA) or titrated insulin glargine (INS). The primary end point was change in glycated hemoglobin A1c (HbA1c) from baseline to week 24. DAPA + SAXA treatment was tested for noninferiority versus INS.

RESULTS
The efficacy data set included 643 patients (mean ± SD HbA1c, 9.1 ± 1.0% [75 ± 11 mmol/mol]). At week 24, DAPA + SAXA treatment versus INS resulted in noninferior reductions in HbA1c (adjusted mean ± SE change, −1.7 ± 0.1% vs. −1.5 ± 0.1% [18.3 ± 0.7 mmol/mol vs. 16.8 ± 0.7 mmol/mol]; P = 0.118), significantly different body weight change (between-group difference, −3.64 kg [95% CI −4.20 to −3.09]; P &lt; 0.001), fewer patients with confirmed hypoglycemia (21.3% vs. 38.4%, P &lt; 0.001), more patients achieving HbA1c &lt;7.0% (53 mmol/mol) without hypoglycemia (20.9% vs. 13.1%, P = 0.008), and a similar proportion of patients achieving HbA1c &lt;7.0% (33.2% vs. 33.5%, P = 0.924). Mean reductions in 24-h glucose measurements from baseline to week 2 were greater with DAPA + SAXA than with INS (P &lt; 0.0001). No patients in the DAPA + SAXA group and three patients (0.9%) in the INS group experienced severe hypoglycemia.

CONCLUSIONS
Adding DAPA + SAXA to insulin-naive patients with poorly controlled type 2 diabetes achieved similar glycemic control, a lower risk of hypoglycemia, and a clinically relevant body weight difference compared with basal INS.
3D Printing in Dentistry—State of the Art
Authors: Kessler A , Hickel R , Reymus M 
Published: June 2019

SUMMARY
Three-dimensional (3D) printing is a rapidly developing technology that has gained widespread acceptance in dentistry. Compared to conventional (lost-wax technique) and subtractive computer numeric controlled methods, 3D printing offers process engineering advantages. Materials such as plastics, metals, and ceramics can be manufactured using various techniques. 3D printing was introduced over three decades ago. Today, it is experiencing rapid development due to the expiration of many patents and is often described as the key technology of the next industrial revolution. The transition to its clinical application in dentistry is highly dependent on the available materials, which must not only provide the required accuracy but also the necessary biological and physical properties. The aim of this work is to provide an up-to-date overview of the different printing techniques: stereolithography, digital light processing, photopolymer jetting, material jetting, binder jetting, selective laser sintering, selective laser melting, and fused filament fabrication. Additionally, particular attention is paid to the materials used in dentistry and their clinical application.
Effects of postprandial hydroxytyrosol and derivates on oxidation of LDL, cardiometabolic state and gene expression: a nutrigenomic approach for cardiovascular prevention
Authors: Perrone Marco A. , Gualtieri Paola , Gratteri Santo , Ali Wahid , Sergi Domenico , Muscoli Saverio , Cammarano Andrea , Bernardini Sergio , Di Renzo Laura , Romeo Francesco 
Published: June 2019

Background and aim
Cardiovascular diseases (CVDs) are the most frequent causes of death in the world. Inflammation and oxidative damage contribute significantly to the development of atherosclerosis and CVDs. European Food Safety Authority scientific opinion has acknowledged that hydroxytyrosol (3,4-dihydroxyphenylethanol) and derivatives, contained in extra virgin olive oil (EVOO), typically used in Mediterranean diet may play a crucial role in the reduction of the inflammatory pathway and in the prevention of CVDs. The aim of the study was to determine the effect in healthy volunteers of 25 g of phenols-rich EVOO (p-EVOO).

Methods
The clinical study was a randomized, controlled trial to determine the acute effect in the postprandial time of 25 g of p-EVOO. We evaluated nutritional status using anthropometric parameters, body composition, serum metabolites, oxidative stress biomarkers and gene expression of eight genes related to oxidative stress and human inflammasome pathways, lasting 2 h after p-EVOO administration. Twenty-two participants resulted as eligible for the study.

Results
A significant reduction of oxidized LDL, malondialdehyde, triglycerides and visceral adiposity index was highlighted (P < 0.05). Significant upregulation of catalase, superoxide dismutase 1 and upstream transcription factor 1 were observed (P < 0.05).

Conclusion
The current study shows that intake of 25 g of p-EVOO has been able to be modulated, in the postprandial time, the antioxidant profile and the expression of inflammation and oxidative stress-related genes, as superoxide dismutase 1, upstream transcription factor 1 and catalase. We also observed a significant reduction of oxidized LDL, malondialdehyde, triglycerides and visceral adiposity index. We have demonstrated that a daily intake of phenols and antioxidants can reduce the inflammatory pathway and oxidative stress and therefore the risk of atherosclerosis and CVDs. More studies on a larger population are necessary before definitive conclusions can be drawn.

Trial registration ClinicalTrials.gov NCT01890070.
Evolution over 11 years of the characteristics of walk-in patients at the emergency department of a university hospital in Brussels
Authors: Hysenbegasi Merita ,   Department of Family Medicine and Chronic Care, Vrije Universiteit Brussel, Belgium, Hubloue Ives ,   Department of Emergency Medicine UZ Brussel and Research Group on Emergency and Disaster Medicine, Vrije Universiteit Brussel, Belgium, Vanobberghen Rita ,   Department of Family Medicine and Chronic Care, Vrije Universiteit Brussel, Belgium, Kartounian Jan ,   Department of Family Medicine and Chronic Care, Vrije Universiteit Brussel, Belgium, Devroey Dirk ,   Department of Family Medicine and Chronic Care, Vrije Universiteit Brussel, Belgium,   Corresponding Author: Dirk Devroey Vrije Universiteit Brussel (VUB), Head of the Dept of Family Medicine and Chronic Care, Laarbeeklaan 103, B-1090 Brussels, Belgium. Tel.: +32 2 477 43 11, Fax: +32 2 477 43 01; E-mail: dirk.devroey@vub.ac.be
Published: June 2019

Walk-in patients who do not require urgent treatment at an emergency department (ED) are a known and long-standing problem.
This study aims to investigate the characteristics of walk-in patients visiting the ED over time.
During four days in June 2012, all walk-in patients attending the ED of the University Hospital Brussels between 8 AM and 11 PM were recorded. A similar registration took place in the same ED in June 2001. Patients completed a questionnaire about their characteristics and the reason for the encounter. Data of both study periods were compared.
The mean age of the patients attending the ED was significantly lower in 2001 (40.9 years) than in 2012 (43.9 years) (p=0,02). In 2001, 81% of the participants had Belgian nationality, but in 2012 this proportion increased to 90% (p=0.008). In 2001 as well as in 2012, 21% of the participants had a referral from their family physician (FP) (p=0.9). The proportion of patients that were aware that FP could also handle some emergencies increased from 17% in 2001 to 29% in 2012 (p=0.003). More patients had complaints that begun less than 24h before they attended the ED (48% in 2001 and 58% in 2012) (p=0.03).
The walk-in patients at the ED are getting slightly older and are attending the ED faster after the onset of the complaints. More patients judge their complaints as urgent. However, more patients are getting aware that FP also could handle some emergencies.
ANÁLISE DA DINÂMICA DELIBERATIVA DE CONSELHOS MUNICIPAIS DE SAÚDE DA REGIÃO CENTRAL DO BRASIL
Authors: De Moura Luciana Melo , Shimizu Helena Eri 
Published: June 2019

Objetivo: avaliar os conselhos municipais de saúde da Região Integrada de Desenvolvimento do Distrito Federal e Entorno quanto à dinâmica deliberativa. Metodologia: Trata-se de um estudo exploratório com abordagem qualitativa. A coleta de dados ocorreu por meio dos documentos de oito conselhos municipais de saúde selecionados, do diário de campo fruto da observação participante das reuniões ordinárias e extraordinárias, bem como das entrevistas em profundidade com os presidentes dos conselhos municipais, cujo tema versou sobre a participação social. Os dados coletados foram organizados e submetidos a análise de conteúdo. Resultados: a síntese dos resultados prediz a existência de uma dinâmica deliberativa nos conselhos municipais de saúde estudados. Contribuições: demonstrou-se que os conselhos municipais estudados têm potencial deliberativo e que podem contribuir para produzir políticas de saúde que atendem aos interesses de atores políticos.
Generalidades y manejo correcto de la hoja de enfermería
Authors: Mayorga-Ponce Rocío B. , Martínez-Alamilla Abigail , Salazar-Valdez Daniela , Pérez-Hernández Jossajandy , Ramírez-Gutierrez Viridiana , Gayosso-Islas Evila 
Published: June 2019

La hoja de enfermería es la evidencia escrita de los cuidados de enfermería y atención que es brindada al paciente, además actúa como medio de comunicación escrita entre los profesionales de enfermería Tomas (1996) y Ramos (1990).
Los registros de enfermería constituyen una parte fundamental de la asistencia en salud, estando integrados en la hoja de enfermería que forma parte del expediente clínico del paciente, lo que conlleva repercusiones y responsabilidades de índole profesional y legal, que precisa llevarlos a la práctica con el necesario rigor científico, que garantice la calidad de los mismos.
Analisis Pernikahan Usia Dini di Kabupaten Bengkulu Tengah Tahun 2017
Authors: Pratiwi Bintang Agustina , Angraini Wulan , Padila Padila , Nopiawati Nopiawati , Yandrizal Yandrizal 
Published: June 2019

The purpose of this study was to determine the cause of the incidence of early pregnancy recording in Bengkulu Tengah Regency. This study used a qualitative approach by revealing informants as many as 7 people using Purposive Sampling techniques in Central Bengkulu District. The latest information obtained is analyzed. Informants married early because there were no other activities after graduating from school, not understood from getting married, wanting to have a mate, not being a parent, there was encouragement from parents. Public media is used as a communication tool, to determine the date of dating. Environmental factors are the reason for informants to marry early in the morning, assuming marriage at an early age is normal. Lack of attention and sensitivity of parents to the problems being experienced by children due to busy working on plantations. The desire of oneself is also a factor of choice for informants to get married at an early age. The relationship between the KUA, the Health Office, the Education Office to provide assistance to the families of prospective teenagers and adolescents. In addition, the need for activeness from community leaders in controlling adolescents in the village.
Keywords: Early Marriage, Media, Knowledge, Environment, Parents
Impact of 68Ga-DOTATOC PET/MRI on robotic radiosurgery treatment planning in meningioma patients: first experiences in a single institution
Authors: Acker Güliz , Kluge Anne , Lukas Mathias , Conti Alfredo , Pasemann Diana , Meinert Franziska , Anh Nguyen Phuong Thuy , Jelgersma Claudius , Loebel Franziska , Budach Volker , Vajkoczy Peter , Furth Christian , Baur Alexander D. J. , Senger Carolin 
Published: June 2019

OBJECTIVEFor stereotactic radiosurgery (SRS) planning, precise contouring of tumor boundaries and organs at risk is of utmost importance. Correct interpretation of standard neuroimaging (i.e., CT and MRI) can be challenging after previous surgeries or in cases of skull base lesions with complex shapes. The aim of this study was to evaluate the impact of 68Ga-DOTATOC PET/MRI on treatment planning for image-guided SRS by CyberKnife.METHODSThe authors retrospectively identified 11 meningioma treatments in 10 patients who received a 68Ga-DOTATOC PET/MRI prior to SRS. The planning target volume (PTV) used for the patients’ treatment was defined as the reference standard. This was contoured by a treating radiosurgeon (RS0) using fused planning CT and PET/MRI data sets. The same tumors were then contoured by another experienced radiosurgeon (RS1) and by a less-experienced radiosurgeon (RS2), both blinded to PET data sets. A comparison of target volumes with focus on volume-based metrics and distance to critical structures was performed. RS1 and RS2 also filled in a questionnaire analyzing the confidence level and the subjective need for the implementation of PET data sets for contouring.RESULTSAnalysis showed a subjective personal preference for PET/MRI in all cases for both radiosurgeons, particularly in proximity to critical structures. The analysis of the planning volumes per physician showed significantly smaller RS2-PTV in comparison to RS1-PTV and to RS0-PTV, whereas the median volumes were comparable between RS1-PTV and RS2-PTV (median: RS0: 4.3 cm3 [IQR 3.4–6.5 cm3] and RS1: 4.5 cm3 [IQR 2.7–6 cm3] vs RS2: 2.6 cm3 [IQR 2–5 cm3]; p = 0.003). This was also reflected in the best spatial congruency between the 2 experienced physicians (RS0 and RS1). The percentage of the left-out volume contoured by RS1 and RS2 compared to RS0 with PET/MRI demonstrated a relevant left-out-volume portion in both cases with greater extent for the less-experienced radiosurgeon (RS2) (RS1: 19.1% [IQR 8.5%–22%] vs RS2: 40.2% [IQR 34.2%–53%]). No significant differences were detected regarding investigated critical structures.CONCLUSIONSThis study demonstrated a relevant impact of PET/MRI on target volume delineation of meningiomas. The extent was highly dependent on the experience of the treating physician. This preliminary study supports the relevance of 68Ga-DOTATOC PET/MRI as a tool for radiosurgical treatment planning of meningiomas.
Management trends for anaplastic meningioma with adjuvant radiotherapy and predictors of long-term survival
Authors: Alhourani Ahmad , Aljuboori Zaid , Yusuf Mehran , Woo Shiao Y. , Hattab Eyas M. , Andaluz Norberto , Williams Brian J. 
Published: June 2019

OBJECTIVEThe purpose of this study was to describe effects of adjuvant radiotherapy (RT) for anaplastic meningiomas (AMs) on long-term survival, and to analyze patient and RT characteristics associated with long-term survival.METHODSThe authors queried a retrospective cohort of patients with AM from the National Cancer Database (NCDB) diagnosed between 2004 and 2015 to describe treatment trends. For outcome analysis, patients with at least 10 years of follow-up were included, and they were stratified based on adjuvant RT status and propensity matched to controls for covariates. Survival curves were compared. A data-driven approach was used to find a biologically effective dose (BED) of RT with the largest difference between survival curves. Factors associated with long-term survival were quantified.RESULTSThe authors identified 2170 cases of AM in the NCDB between 2004 and 2015. They observed increased use of adjuvant RT in patients treated with higher doses. A total of 178 cases met the inclusion criteria for outcome analysis. Forty-five percent (n = 80) received adjuvant RT. Patients received a BED of 80.23 ± 16.6 Gy (mean ± IQR). The median survival time was not significantly different (32.8 months for adjuvant RT vs 38.5 months for no RT; p = 0.57, log-rank test). Dichotomizing the patients at a BED of 81 Gy showed maximal difference in survival distribution with a decrease in median survival in favor of no adjuvant RT (31.2 months for adjuvant RT vs 49.7 months for no RT; p = 0.03, log-rank test), but this difference was not significant after false discovery rate correction. Age was a significant predictor for long-term survival.CONCLUSIONSAMs are aggressive tumors that carry a poor prognosis. Conventional adjuvant RT improves local control. However, the effect of adjuvant radiation on overall survival is unclear. Further investigation into this area is warranted.
Efficacy and toxicity of particle radiotherapy in WHO grade II and grade III meningiomas: a systematic review
Authors: Wu Adela , Jin Michael C. , Meola Antonio , Wong Hong-nei , Chang Steven D. 
Published: June 2019

OBJECTIVEAdjuvant radiotherapy has become a common addition to the management of high-grade meningiomas, as immediate treatment with radiation following resection has been associated with significantly improved outcomes. Recent investigations into particle therapy have expanded into the management of high-risk meningiomas. Here, the authors systematically review studies on the efficacy and utility of particle-based radiotherapy in the management of high-grade meningioma.METHODSA literature search was developed by first defining the population, intervention, comparison, outcomes, and study design (PICOS). A search strategy was designed for each of three electronic databases: PubMed, Embase, and Scopus. Data extraction was conducted in accordance with the PRISMA guidelines. Outcomes of interest included local disease control, overall survival, and toxicity, which were compared with historical data on photon-based therapies.RESULTSEleven retrospective studies including 240 patients with atypical (WHO grade II) and anaplastic (WHO grade III) meningioma undergoing particle radiation therapy were identified. Five of the 11 studies included in this systematic review focused specifically on WHO grade II and III meningiomas; the others also included WHO grade I meningioma. Across all of the studies, the median follow-up ranged from 6 to 145 months. Local control rates for high-grade meningiomas ranged from 46.7% to 86% by the last follow-up or at 5 years. Overall survival rates ranged from 0% to 100% with better prognoses for atypical than for malignant meningiomas. Radiation necrosis was the most common adverse effect of treatment, occurring in 3.9% of specified cases.CONCLUSIONSDespite the lack of randomized prospective trials, this review of existing retrospective studies suggests that particle therapy, whether an adjuvant or a stand-alone treatment, confers survival benefit with a relatively low risk for severe treatment-derived toxicity compared to standard photon-based therapy. However, additional controlled studies are needed.