bluuebunny/crossref_metadata_2025 huggingface dataset:
“The Therapy of Elimination First” for Early Acute Mastitis: A Systematic Review and Meta‐Analysis
Authors: Zhang Ying , Sun Xiaoying , Li Kexin , Wang Xiaomin , Cai Lijun , Li Xin , Zhou Min
Published: May 2018

We evaluated the effectiveness of “the therapy of elimination first” in early acute mastitis, using four databases (CNKI, Wanfang, Embase, and PubMed). The study incorporated 2508 patients from 16 randomized controlled trials (RCTs). Included trials used Chinese oral medicine and applied the principle of “Eliminating Therapy” for the early treatment of acute mastitis, with simple antibiotic treatment as a control group. Meta‐analysis showed significant differences between the overall effectiveness of oral Chinese medicine using Eliminating Therapy (OCM‐ET) and western medicine using antibiotics (WM‐A) (odds ratio [OR] = 4.43, 95% confidence interval [CI] = 3.21–6.12, Z = 9.04, and P < 0.00001). Analysis of subgroups based on the use of classic or self‐made preparations of the medicines showed smaller statistical heterogeneity among the different subgroups (P > 0.05, I2 ≤ 50%). The OCM‐ET group showed significantly shorter pain relief times [mean difference (MD) = −3.08, 95% CI = (−5.90, −0.26), and P = 0.03] and cure times [MD = −6.27, 95% CI = (−9.68, −2.85), and P = 0.0003] than did the WM‐A group. Our findings suggest that OCM‐ET can shorten the duration of pain and improve cure time in early acute mastitis patients, with fewer adverse reactions. However, RCTs of higher quality with larger sample sizes are required to confirm these findings.
Dicalcium Silicate Induced Proinflammatory Responses through TLR2-Mediated NF-κB and JNK Pathways in the Murine RAW 264.7 Macrophage Cell Line
Authors: Lai Shixiang , Chen Liangjiao , Cao Wei , Cui Shiman , Li Xingyang , Zhong Wenchao , Ma Mingyu , Zhang Qingbin
Published: May 2018

Proinflammatory responses are important aspects of the immune response to biomaterials, which may cause peri-implantitis and implant shedding. The purpose of this study was to test the cytotoxicity and proinflammatory effects of dicalcium silicate particles on RAW 264.7 macrophages and to investigate the proinflammatory response mechanism induced by C2S and tricalcium phosphate (TCP). C2S and TCP particles were characterized using scanning electron microscopy (SEM), energy spectrum analysis (EDS) and X-ray diffraction (XRD). Cytotoxicity and apoptosis assays with C2S and TCP in the murine RAW 264.7 cell line were tested using the cell counting kit-8 (CCK-8) assay and flow cytometry (FCM). The detection results showed that C2S and TCP particles had no obvious toxicity in RAW 264.7 cells and did not cause obvious apoptosis, although they both caused an oxidative stress response by producing ROS when the concentrations were at 100 μg/mL. C2S particles are likely to induce a proinflammatory response by inducing high TLR2, TNF-αmRNA, TNF-αproinflammatory cytokine, p-IκB, and p-JNK1 + JNK2 + JNK3 expression levels. When we added siRNA-TLR2-1, a significant reduction was observed. These findings support the theory that C2S particles induce proinflammatory responses through the TLR2-mediated NF-κB and JNK pathways in the murine RAW 264.7 macrophage cell line.
A Worksite Nutrition Intervention is Effective at Improving Employee Well-Being: A Pilot Study
Authors: Sutliffe Jay T. , Carnot Mary Jo , Fuhrman Joel H. , Sutliffe Chloe A. , Scheid Julia C.
Published: May 2018

Background. Worksite dietary interventions show substantial potential for improving employee health and well-being. The aim of this pilot study was to determine the effect of a worksite nutrition intervention on improving well-being. Methods. Thirty-five university employees participated in a 6-week nutrition intervention. The dietary protocol emphasized the daily consumption of greens, beans/legumes, a variety of other vegetables, fruits, nuts, seeds, and whole grains, referred to as a micronutrient-dense, plant-rich diet. Participants were encouraged to minimize the consumption of refined foods and animal products. Results. Significant improvements in sleep quality, quality of life, and depressive symptoms were found. Conclusions. Findings reveal that a worksite nutrition intervention is effective at improving sleep quality, quality of life, and depressive symptoms with a projected improvement in work productivity and attendance.
A Computing Method to Determine the Performance of an Ionic Liquid Gel Soft Actuator
Authors: He Bin , Zhang Chenghong , Zhou Yanmin , Wang Zhipeng
Published: May 2018

A new type of soft actuator material—an ionic liquid gel (ILG) that consists of BMIMBF4, HEMA, DEAP, and ZrO2—is polymerized into a gel state under ultraviolet (UV) light irradiation. In this paper, we first propose that the ILG conforms to the assumptions of hyperelastic theory and that the Mooney-Rivlin model can be used to study the properties of the ILG. Under the five-parameter and nine-parameter Mooney-Rivlin models, the formulas for the calculation of the uniaxial tensile stress, plane uniform tensile stress, and 3D directional stress are deduced. The five-parameter and nine-parameter Mooney-Rivlin models of the ILG with a ZrO2 content of 3 wt% were obtained by uniaxial tensile testing, and the parameters are denoted as c10, c01, c20, c11, and c02 and c10, c01, c20, c11, c02, c30, c21, c12, and c03, respectively. Through the analysis and comparison of the uniaxial tensile stress between the calculated and experimental data, the error between the stress data calculated from the five-parameter Mooney-Rivlin model and the experimental data is less than 0.51%, and the error between the stress data calculated from the nine-parameter Mooney-Rivlin model and the experimental data is no more than 8.87%. Hence, our work presents a feasible and credible formula for the calculation of the stress of the ILG. This work opens a new path to assess the performance of a soft actuator composed of an ILG and will contribute to the optimized design of soft robots.
A Giant Gastroschisis Associated with Pulmonary Hypoplasia and Spinal Anomaly: A Case Report and a Literature Review
Authors: Puvabanditsin Surasak , Burger Robin , Puthenpura Vidya , Walzer Lauren , Madubuko Adaora , Minerowicz Christine , Mehta Rajeev
Published: May 2018

Gastroschisis most often occurs as an isolated anomaly and extragastrointestinal associations are rare. Most commonly, the anomalies associated with gastroschisis are cardiac and central nervous system abnormalities. Respiratory insufficiency has sometimes been reported in association with giant abdominal wall defects. Poor outcomes and prolonged ventilator support have been reported in giant gastroschisis and omphalocele, especially if associated with herniation of the majority of the liver. We report a case of a large gastroschisis that was associated with a kyphoscoliosis and pulmonary hypoplasia.
The Impact of Whole Body Vibration Therapy on Spasticity and Disability of the Patients with Poststroke Hemiplegia
Authors: Alp Alev , Efe Bilge , Adalı Mihriban , Bilgiç Adnan , Demir Türe Sevda , Coşkun Şeyma , Karabulut Merve , Ertem Uğur , Günay Selim Mahmut
Published: May 2018

Objective. To determine if whole body vibration therapy (WBV) effectively improves functional outcome in patients with poststroke hemiplegia. Materials and Methods. In this single-blind RCT, WBV group (n=10) had 40 hz frequency/4 mm amplitude vibration during 5 minutes/session, 3 days a week, for a duration of 4 weeks. The control group (n=11) had no vibration therapy for the same duration while standing on the same platform. Patients in both of the groups did 15 minutes of stretching and active range of motion exercises before the intervention. Outcome measures were Modified Ashworth Scale (MAS), Functional Independence Measurement (FIM), and Timed 10-Meter Walk Test (10 mWT). Results. Only 10 mWT improved at the 1st week (p=0.002), 1st month (p<0.001), and 3rd month (p<0.001) in favor of the intervention group. There was positive correlation also between 10 mWT and ankle spasticity (p<0.001, r=0.931). Conclusion. This study suggests that WBV therapy may be a complementary therapy in gait rehabilitation and functional outcome of the patients with calf muscle spasticity.
Optimization and Validation of Thermal Desorption Gas Chromatography-Mass Spectrometry for the Determination of Polycyclic Aromatic Hydrocarbons in Ambient Air
Authors: Elorduy Iñaki , Durana Nieves , García José Antonio , Gómez María Carmen , Alonso Lucio
Published: May 2018

Thermal desorption (TD) coupled with gas chromatography/mass spectrometry (TD-GC/MS) is a simple alternative that overcomes the main drawbacks of the solvent extraction-based method: long extraction times, high sample manipulation, and large amounts of solvent waste. This work describes the optimization of TD-GC/MS for the measurement of airborne polycyclic aromatic hydrocarbons (PAHs) in particulate phase. The performance of the method was tested by Standard Reference Material (SRM) 1649b urban dust and compared with the conventional method (Soxhlet extraction-GC/MS), showing a better recovery (mean of 97%), precision (mean of 12%), and accuracy (±25%) for the determination of 14 EPA PAHs. Furthermore, other 15 nonpriority PAHs were identified and quantified using their relative response factors (RRFs). Finally, the proposed method was successfully applied for the quantification of PAHs in real 8 h-samples (PM10), demonstrating its capability for determination of these compounds in short-term monitoring.
Detection of Organophosphorus Pesticides in Wheat by Ionic Liquid-Based Dispersive Liquid-Liquid Microextraction Combined with HPLC
Authors: Liu Wei , Quan Ji , Hu Zeshu
Published: May 2018

Food safety issues closely related to human health have always received widespread attention from the world society. As a basic food source, wheat is the fundamental support of human survival; therefore, the detection of pesticide residues in wheat is very necessary. In this work, the ultrasonic-assisted ionic liquid-dispersive liquid-liquid microextraction (DLLME) method was firstly proposed, and the extraction and analysis of three organophosphorus pesticides were carried out by combining high-performance liquid chromatography (HPLC). The extraction efficiencies of three ionic liquids with bis(trifluoromethylsulfonyl)imide (Tf2N) anion were compared by extracting organophosphorus in wheat samples. It was found that the use of 1-octyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([OMIM][Tf2N]) had both high enrichment efficiency and appropriate extraction recovery. Finally, the method was used for the determination of three wheat samples, and the recoveries of them were 74.8–112.5%, 71.8–104.5%, and 83.8–115.5%, respectively. The results show that the method proposed is simple, fast, and efficient, which can be applied to the extraction of organic matters in wheat samples.
Numerical Investigation on Hydraulic Properties of Artificial-Splitting Granite Fractures during Normal and Shear Deformations
Authors: Xiong Feng , Jiang Qinghui , Chen Mingxi
Published: May 2018

This study explores the effects of normal loading and shearing on hydraulic properties in roughness-walled rock fractures. The geometries of five fractures were measured by the 3D scanning technology. The flow simulation was performed for rough rock fractures with large displacements during normal loading and shearing by finite volume method (FVM). The results demonstrate that the deformation of fracture with increasing normal stress and shear causes nonuniform changes in void space geometry and further influences fracture permeability. Associated with normal displacement are an increase in contact area and a decrease in mechanical aperture. The transmissivity is decreasing by 3 orders of magnitude response to applied normal displacement values of 0.0 mm to 1.8 mm. In contrast, an increase in mechanical aperture and contact ratio that occurs with increasing shear displacement values of 0.0 mm to 4.0 mm is associated with decreasing distinctly transmissivity by 1.5–2 orders of magnitude. Based on the numerical results, an empirical equation is proposed to evaluate the effects of contact area and roughness of fracture on the hydraulic aperture. The good agreement between numerical results and the predicted results by the new model indicates that the proposed model is capable of estimating the hydraulic aperture of rock fractures through parametric analyses, compared with other published models from available literature. In addition, the new model succeeds in predicting the transmissivity in Develi and Babadagli (2014) water flow experiments.
The Potential Growing Areas for Argania spinosa (L.) Skeels (Sapotaceae) in Argentinean Drylands
Authors: Falasca Silvia L. , Pitta-Alvarez Sandra , Ulberich Ana
Published: May 2018

The argan (Argania spinosa L.) tree is indigenous to southwestern Morocco. Successful introduction of this species in Argentina depends on the degree of climate similarity in the natural area compared to new areas with agroclimatic suitability. Based on international bibliography, the authors outlined an agroclimatic zoning model for this tree in Argentina. To determine agroclimatic suitability, the average climatic data of all the meteorological stations (1981–2010) were analyzed. Climatological characteristics of its region of origin were considered to evaluate the requirements and biometeorological conditions. The maps were obtained using a series of previously interpolated bioclimatic variables. The agroclimatic indices, which determine different classes of suitability, were integrated in a Geographic Information System (GIS) to create thermal and moisture regions. The resulting maps were superimposed to determine the agroclimatic zoning. Eight classes of agroclimatic suitability under dry-subhumid, semiarid, and arid climatic conditions were delineated. There are no optimal zones for the argan tree in Argentina. This work can be updated by further incorporation of complementary information. Argan tree is a promising dryland crop for farmers in semiarid and arid climates of Argentina. This model may be applied in any part of the world, using the agroclimatic limits presented in this paper.
Amelioration of Single Clove Black Garlic Aqueous Extract on Dyslipidemia and Hepatitis in Chronic Carbon Tetrachloride Intoxicated Swiss Albino Mice
Authors: Tran Gia-Buu , Dam Sao-Mai , Le Nghia-Thu Tram
Published: May 2018

Single clove garlic is the product of atypical bulbing process of garlic under specific conditions. Therefore, the number of researches on single clove garlic bioactivity is limited. Recently, the hepatoprotective effect of single clove garlic has been demonstrated. In this study, we investigated amelioration of single clove black garlic aqueous extract, a processed product from single clove garlic, on dyslipidemia and hepatitis induced by chronic administration of CCl4. Mice were randomly divided into four groups: control, extract control, CCl4 intoxication, and coadministrated CCl4 and extract group. Mice were orally given a dose of 1 ml/kg body weight of CCl4 for 28 days twice a week to establish chronic liver injury model. To evaluate the hepatoprotective effect of single clove black garlic, mice were cotreated with CCl4 and single clove black garlic extract (200 mg/kg body weight) via gastric gauge for 30 days. Cotreatment with CCl4 and extract could improve the changes of body weight, liver weight, and relative liver weight as compared to CCl4 intoxicated mice. Single clove black garlic ameliorated dyslipidemia and the elevation of ALT and AST levels induced by chronic CCl4 intoxication. Histological studies revealed that single clove black garlic could prevent mononuclear cells infiltration and hepatocyte necrosis.
Astragalin: A Bioactive Phytochemical with Potential Therapeutic Activities
Authors: Riaz Ammara , Rasul Azhar , Hussain Ghulam , Zahoor Muhammad Kashif , Jabeen Farhat , Subhani Zinayyera , Younis Tahira , Ali Muhammad , Sarfraz Iqra , Selamoglu Zeliha
Published: May 2018

Natural products, an infinite treasure of bioactive chemical entities, persist as an inexhaustible resource for discovery of drugs. This review article intends to emphasize on one of the naturally occurring flavonoids, astragalin (kaempferol 3-glucoside), which is a bioactive constituent of various traditional medicinal plants such as Cuscuta chinensis. This multifaceted compound is well known for its diversified pharmacological applications such as anti-inflammatory, antioxidant, neuroprotective, cardioprotective, antiobesity, antiosteoporotic, anticancer, antiulcer, and antidiabetic properties. It carries out the aforementioned activities by the regulation and modulation of various molecular targets such as transcription factors (NF-κB, TNF-α, and TGF-β1), enzymes (iNOS, COX-2, PGE2, MMP-1, MMP-3, MIP-1α, COX-2, PGE-2, HK2, AChe, SOD, DRP-1, DDH, PLCγ1, and GPX), kinases (JNK, MAPK, Akt, ERK, SAPK, IκBα, PI3K, and PKCβ2), cell adhesion proteins (E-cadherin, vimentin PAR-2, and NCam), apoptotic and antiapoptotic proteins (Beclin-1, Bcl-2, Bax, Bcl-xL, cytochrome c, LC3A/B, caspase-3, caspase-9, procaspase-3, procaspase-8, and IgE), and inflammatory cytokines (SOCS-3, SOCS-5, IL-1β, IL-4, IL-6, IL-8, IL-13, MCP-1, CXCL-1, CXCL-2, and IFN-γ). Although researchers have reported multiple pharmacological applications of astragalin in various diseased conditions, further experimental investigations are still mandatory to fully understand its mechanism of action. It is contemplated that astragalin could be subjected to structural optimization to ameliorate its chemical accessibility, to optimize its absorption profiles, and to synthesize its more effective analogues which will ultimately lead towards potent drug candidates.
A Raf-Competitive K-Ras Binder Can Fail to Functionally Antagonize Signaling
Authors: Kauke Monique J. , Tisdale Alison W. , Kelly Ryan L. , Braun Christian J. , Hemann Michael T. , Wittrup K. Dane
Published: May 2018

Mutated in approximately 30% of human cancers, Ras GTPases are the most common drivers of oncogenesis and render tumors unresponsive to many standard therapies. Despite decades of research, no drugs directly targeting Ras are currently available. We have previously characterized a small protein antagonist of K-Ras, R11.1.6, and demonstrated its direct competition with Raf for Ras binding. Here we evaluate the effects of R11.1.6 on Ras signaling and cellular proliferation in a panel of human cancer cell lines. Through lentiviral transduction, we generated cell lines that constitutively or through induction with doxycycline express R11.1.6 or a control protein YW1 and show specific binding by R11.1.6 to endogenous Ras through microscopy and co-immunoprecipitation experiments. Genetically encoded intracellular expression of this high-affinity Ras antagonist, however, fails to measurably disrupt signaling through either the MAPK or PI3K pathway. Consistently, cellular proliferation was unaffected as well. To understand this lack of signaling inhibition, we quantified the number of molecules of R11.1.6 expressed by the inducible cell lines and developed a simple mathematical model describing the competitive binding of Ras by R11.1.6 and Raf. This model supports a potential mechanism for the lack of biological effects that we observed, suggesting stoichiometric and thermodynamic barriers that should be overcome in pharmacologic efforts to directly compete with downstream effector proteins localized to membranes at very high effective concentrations. Mol Cancer Ther; 17(8); 1773–80. ©2018 AACR.
CAR-T Cells Surface-Engineered with Drug-Encapsulated Nanoparticles Can Ameliorate Intratumoral T-cell Hypofunction
Authors: Siriwon Natnaree , Kim Yu Jeong , Siegler Elizabeth , Chen Xianhui , Rohrs Jennifer A. , Liu Yarong , Wang Pin
Published: May 2018

One limiting factor of CAR T-cell therapy for treatment of solid cancers is the suppressive tumor microenvironment (TME), which inactivates the function of tumor-infiltrating lymphocytes (TIL) through the production of immunosuppressive molecules, such as adenosine. Adenosine inhibits the function of CD4+ and CD8+ T cells by binding to and activating the A2a adenosine receptor (A2aR) expressed on their surface. This suppression pathway can be blocked using the A2aR-specific small molecule antagonist SCH-58261 (SCH), but its applications have been limited owing to difficulties delivering this drug to immune cells within the TME. To overcome this limitation, we used CAR-engineered T cells as active chaperones to deliver SCH-loaded cross-linked, multilamellar liposomal vesicles (cMLV) to tumor-infiltrating T cells deep within the immune suppressive TME. Through in vitro and in vivo studies, we have demonstrated that this system can be used to effectively deliver SCH to the TME. This treatment may prevent or rescue the emergence of hypofunctional CAR-T cells within the TME. Cancer Immunol Res; 6(7); 812–24. ©2018 AACR.
Performance of Phonatory Deviation Diagrams in Synthesized Voice Analysis
Authors: Lopes Leonardo Wanderley , da Silva Karoline Evangelista , da Silva Evangelista Deyverson , Almeida Anna Alice , Silva Priscila Oliveira Costa , Lucero Jorge , Behlau Mara
Published: May 2018

Objective: To analyze the performance of a phonatory deviation diagram (PDD) in discriminating the presence and severity of voice deviation and the predominant voice quality of synthesized voices. Method: A speech-language pathologist performed the auditory-perceptual analysis of the synthesized voice (n = 871). The PDD distribution of voice signals was analyzed according to area, quadrant, shape, and density. Results: Differences in signal distribution regarding the PDD area and quadrant were detected when differentiating the signals with and without voice deviation and with different predominant voice quality. Differences in signal distribution were found in all PDD parameters as a function of the severity of voice disorder. Conclusion: The PDD area and quadrant can differentiate normal voices from deviant synthesized voices. There are differences in signal distribution in PDD area and quadrant as a function of the severity of voice disorder and the predominant voice quality. However, the PDD area and quadrant do not differentiate the signals as a function of severity of voice disorder and differentiated only the breathy and rough voices from the normal and strained voices. PDD density is able to differentiate only signals with moderate and severe deviation. PDD shape shows differences between signals with different severities of voice deviation.
Outcomes of Glaucoma Drainage Device Surgery in Eyes with Treated Uveal Melanoma
Authors: Fatehi Nima , McCannel Tara A. , Giaconi JoAnn , Caprioli Joseph , Law Simon K. , Nouri-Mahdavi Kouros
Published: May 2018

Aim: We report patient safety and intraocular pressure (IOP) control after placement of a glaucoma drainage device (GDD) in eyes with a history of treated malignant uveal melanoma. Methods: A retrospective review of the records of patients with uveal melanoma was performed. Outcomes were local tumor recurrence, rate of metastases, and to­nometric success, based on survival curves, defined as IOP < 21 mm Hg. Results: Eleven eyes with choroidal melanoma, 4 with iris melanoma, and 1 with ciliary body melanoma were followed for a median (interquartile range) of 2.1 (1.1–3.2) years. Two subjects developed liver metastases; one had monosomy 3 and tumor gene expression profile class 2. The other case with ciliary body melanoma was negative for monosomy 3. There were no cases of local treatment failure. Mean preoperative IOP decreased from 30.5 ± 7.7 to 15.9 ± 8.1 mm Hg at 1 year after surgery (1-year success rate 80%). Conclusions: Our case series with a median follow-up of 2 years shows that placing a GDD in patients with treated uveal melanoma does not expose patients to greater risk of local or extraocular recurrence. A larger series and longer follow-up time are required to fully evaluate the safety of GDDs in this clinical scenario.
Predicting Sequential Cochlear Implantation Performance: A Systematic Review
Authors: Smulders Yvette E. , Hendriks Thomas , Eikelboom Robert H. , Stegeman Inge , Santa Maria Peter L. , Atlas Marcus D. , Friedland Peter L.
Published: May 2018

This systematic review of the literature reveals which pre­operative factors affect sequential cochlear implantation outcomes in adults. The findings can help health care prof­essionals provide evidence-based advice on the expected benefits from a second cochlear implant (CI). We searched PubMed, EMBASE, and the Cochrane database from November 1977 to August 26, 2017, using the terms “sequential cochlear implantation”; the most frequently cited predictors for unilateral cochlear implantation performance and other potential predictors for sequential implantation outcome; and “speech perception,” “localization” as well as synonyms of all of the above. Ten studies were included. The effects of age, duration of hearing loss, time between implantations, preoperative hearing, etiology of hearing loss, hearing aid use and duration of follow-up on sequential cochlear implantation performance were studied. The literature has shown that duration of deafness, age at onset of deafness, etiology of hearing loss, and preoperative speech perception score are (inversely) related to unilateral cochlear implantation outcome in adults. One would expect that these factors would also affect sequential bilateral implantation outcome. However, the best available evidence to date shows that advanced age, a long duration of deafness, or a long interval between implantations should not be considered negative factors when considering sequential bilateral cochlear implantation.
Prescription Pattern of Proton Pump Inhibitors at Hospital Admission and Discharge
Authors: Gamelas Verónica , Salvado Vera , Dias Luís
Published: May 2018

Background: Proton pump inhibitors (PPI) have reportedly been used in inappropriate clinical settings, often leading to an increased risk of adverse effects, drug interactions, and costs. Aim: The aim of this study was to evaluate the adequacy of PPI prescription in an internal medicine ward. Methods: The discharged home inpatients of a segment in the medicine department of a central hospital in the first trimester of 2017 were evaluated; those who died or were transferred to another unit were excluded. Data on gender, age, admission, and discharge therapy and diagnoses which could support PPI use were collected from clinical records. Statistical analysis was performed using Microsoft Excel 2013® and IBM SPSS Statistics 20®. Results: A total of 318 hospitalizations were included, corresponding to 301 patients; 171 (56.8%) were female and the average age was 75.4 ± 14.6 years. Among the 318 hospitalizations, 148 patients (46.5%) were on PPI at admission and 175 (55%) at discharge, the majority of them without indication (n = 91, 61.5% vs. n = 109, 62.3%). The main inappropriate indication was anticoagulation alone (n = 33, 36.3% vs. n = 43, 39.4%). There was indication for PPI therapy in 93 (29.2%) of the cases at admission and 111 (34.9%) at discharge, mostly for prophylaxis of gastrointestinal bleeding in high-risk patients (n = 82, 88.2% vs. n = 96, 86.5%). Among those with indication, 57 (61.3%) were medicated at admission versus 66 (59%) at discharge. The association between PPI therapy and an indication for its prescription was lost by the time of discharge (p = 0.245). Conclusions: PPI prescription is not in agreement with existing recommendations, which is why it should be revised at hospital discharge. The primary indication for PPI therapy is the prophylaxis of gastrointestinal bleeding in high-risk patients and the main inappropriate indication is prophylaxis in low-risk patients. A large proportion of the patients indicated for PPI use were discharged without prescription.
Successful Treatment of Pityriasis Rubra Pilaris with Ixekizumab
Authors: Hanfstingl Kathrin , Pekar-Lukacs Agnes , Motz Reinhard , Guenova Emmanuella , Hoetzenecker Wolfram
Published: May 2018

Pityriasis rubra pilaris is an inflammatory dermatologic disorder of unknown cause and often confounded with psoriasis. It is characterised by hyperkeratotic follicular papules, scaly erythematous plaques, palmoplantar keratoderma, and a progression to generalised erythroderma. Here, we report the case of a 68-year-old man with pityriasis rubra pilaris, who was successfully treated with ixekizumab, an interleukin-17A inhibitor.
Unfractionated Heparin Alleviates Human Lung Endothelial Barrier Dysfunction Induced by High Mobility Group Box 1 Through Regulation of P38–GSK3β–Snail Signaling Pathway
Authors: Luan Zhenggang , Hu Bo , Wu Lei , Jin Shanzi , Ma Xiaochun , Zhang Jun  , Wang Aiping
Published: May 2018

Background/Aims: The high mobility group box 1 (HMGB1) has been regarded as an important inflammatory mediator. Previous studies showed the involvement of HMGB1 protein in the dysfunction of endothelial barrier function during acute lung injury. However, the molecular mechanism remains unclear. Methods: In this study, we used recombinant human HMGB1 (rhHMGB1) and HMGB1 plasmid to treat human pulmonary microvascular endothelial cell (HPMECs). We examined endothelial permeability by measuring TEER value and HRP flux. Western blot and real-time PCR were used to examined change of endothelial-to-mesenchymal transition (EndoMT) markers and related pathways. Immunofluorescence was used to examine localization and expression of ZO-1 and VE-cadherin. SB203580.was used to block p38 pathway. Unfractionated heparin (UFH) and RAGE siRNA were also used to antagonize the effect of HMGB1. Results: We showed that HMGB1 induced EndoMT with downregulation of ZO-1 and VE-cadherin at both mRNA and protein levels in HPMECs. We also demonstrated that HMGB1 upregulated endothelial permeability by measuring TEER value and HRP flux. Moreover, HMGB1 activated p38/GSK3β/Snail signaling pathway and treatment with p38 inhibitor SB203580 abolished its biological effects. In addition, we found that UFH was able to reverse the effect of HMGB1 on EndoMT and endothelial permeability through inhibition of p38 signaling in a dose-dependent manner. We discovered that RAGE, a membrane receptor of HMGB1, transduced p38/Snail pathway to EndoMT. RAGE siRNA inhibited the effect of HMGB1 induced EndoMT in HPMECs. Conclusion: The present study demonstrated that HMGB1 induced EndoMT through RAGE receptor and p38/GSK3β/Snail pathway. While UFH antagonized HMGB1 and maintained the integrity of the endothelial barrier through p38 inhibition.
PIK3R3 Promotes Metastasis of Pancreatic Cancer via ZEB1 Induced Epithelial-Mesenchymal Transition
Authors: Peng Yun-Peng , Zhu Yi , Yin Ling-Di , Wei Ji-Shu , Liu Xin-Chun , Zhu Xiao-Le , Miao Yi
Published: May 2018

Background/Aims: PIK3R3 is a regulatory subunit of phosphatidylinositol 3-kinase (PI3K) which plays an essential role in the metastasis of several types of cancer. However, whether PIK3R3 can promote the metastasis of pancreatic cancer (PC) is still unclear. In this study, we characterized the role of PIK3R3 in metastasis of PC and underlying potential mechanisms. Methods: RT-PCR, western blot, immunofluorescence (IF) and immunohistochemistry (IHC) were applied to investigate the expression of genes and proteins in different cell lines and tissues. To assess the function of PIK3R3 and related mechanisms, the cells with RNAi-mediated knockdown or overexpression were used to perform a series of in vitro and in vivo assays. Results: PIK3R3 was significantly overexpressed in pancreatic cancer tissues, especially in metastatic cancer tissues, as well as in pancreatic cancer cells. Functional assays suggested that overexpression or knockdown of PIK3R3 could respectively promote or suppress the migration and invasion of PC cells in vitro and in vivo. Further mechanism related studies demonstrated that ERK1/2-ZEB1 pathway-triggered epithelial-mesenchymal transition (EMT) might be responsible for the PIK3R3-induced PC cell migration and invasion. Conclusion: PIK3R3 could promote the metastasis of PC by facilitating ZEB1 induced EMT, and could act as a potential therapeutic target to limit PC metastasis.
Pioneiros, fundadores e aventureiros – a ocupação de terras em Rondônia
Authors: Cordeiro Manuela Souza Siqueira
Published: May 2018

Na região de Ariquemes, durante a década de 1970, foram implantados dois projetos de assentamento dirigidos (PADs), como parte da iniciativa de colonização do governo militar. Durante as primeiras incursões ao campo, percebi que muito daquilo que me interessava pesquisar sobre Rondônia confluía para uma identificação específica que caracterizava grande parte daqueles que foram responsáveis pela ocupação das terras no estado: o “pioneiro”. Este artigo tem como objetivo problematizar o uso de categorias posicionais ligadas ao processo de transformação da “floresta” em “terra”, isto é, a terra sem valor comercial para a “terra aberta” e, portanto, agricultável, destacando diferentes períodos. No momento da ocupação das terras, os ocupantes se consideravam “aventureiros”, havendo também desdobramento na categoria circunscrita a um momento histórico posterior, a de “fundador”. Na descrição etnográfica trazida para o texto, a partir de conversas realizadas com seis “pioneiros”, salientarei a diferença no uso das referidas categorias.
Da vida baunilha aos êxtases no erotismo contemporâneo: Prazeres perigosos: erotismo, gênero e limites da sexualidade, de Maria Filomena Gregori
Authors: Nelvo Romário Vieira
Published: May 2018

Da vida baunilha aos êxtases no erotismo contemporâneo: Prazeres perigosos: erotismo, gênero e limites da sexualidade, de Maria Filomena Gregori
Effect of somatic cell count on composition and hygiene indicators of bulk tank milk
Authors: Macedo Susana Nori de , Gonçalves Juliano Leonel , Cortinhas Cristina Simões , Leite Renata de Freitas , Santos Marcos Veiga dos
Published: May 2018

This study evaluated the effect of somatic cell count (SCC) on composition and hygienic quality of dairy herd bulk tank milk – specifically, the effect of SCC of bulk tank of dairy herds on composition (fat, protein, total solids, nonfat dry solids) and on total bacterial count (TBC), psychrotrophic count (PC) and coliform count (CC) were evaluated. A total of 230 dairy herds located south of Minas Gerais and west of São Paulo were selected based on SCC geometric mean obtained from five monthly analyses preceding the start of the sampling. The dairy farms were classified according to SCC in three groups: low (< 250,000 cells/mL, n = 84), medium (> 250,000 and < 750,000 cells/mL, n = 79) and highSCC (> 750,000 cells/mL, n = 67). After herd selection, bulk tank milk samples were collected every 14 days for three months totaling 1380 samples, which were subjected to analysis of composition, TBC, PC, and CC. A decrease of TBC and CC was observed in herds with low SCC; however, herds with medium and high SCC had an increase in fat, crude protein, and total solids contents. A medium correlation was observed between TBC and PC (r = 0.6215), and also between PC and CC (r = 0.3692). Based on hygiene indicators and milk composition, a low and negative correlation between TBC and fat (r = -0.0585), PC and fat (r = -0.0585), and PC and total solids (r = -0.0662) was observed. Dairy herds with SCC < 250,000 cells/mL had higher bulk tank milk hygienic quality; however, considering the composition, herds with higher SCC produced higher milk fat and protein concentration.
Notas para argonautas
Authors: Ruggieri Mariana
Published: May 2018

Uma investigação em torno do livro The Argonauts (2015), de Maggie Nelson, e das formas de escrita que podem resultar de sua leitura.
O sonho de uma língua comum: a tradição segundo Adrienne Rich
Authors: Camargo Sarah Valle
Published: May 2018

O artigo aborda aspectos da tradução para o português de Twenty-One Love Poems, de Adrienne Rich (1929-2012), incorporados na obra The Dream of a Common Language (1974-1977). Concentrando-se na ambivalência rítmica, verifica o uso e a recusa da linguagem e da tradição na composição desta que pode ser considerada a primeira sequência de poemas lésbicos escrita por uma grande poeta norte-americana.
Plasma Biomarkers of Inflammation and Angiogenesis Predict Cerebral Cavernous Malformation Symptomatic Hemorrhage or Lesional Growth
Authors: Girard Romuald , Zeineddine Hussein A. , Koskimäki Janne , Fam Maged D. , Cao Ying , Shi Changbin , Moore Thomas , Lightle Rhonda , Stadnik Agnieszka , Chaudagar Kiranj , Polster Sean , Shenkar Robert , Duggan Ryan , Leclerc David , Whitehead Kevin J. , Li Dean Y. , Awad Issam A.
Published: May 2018

Rationale:

The clinical course of cerebral cavernous malformations is highly unpredictable, with few cross-sectional studies correlating proinflammatory genotypes and plasma biomarkers with prior disease severity.

Objective:

We hypothesize that a panel of 24 candidate plasma biomarkers, with a reported role in the physiopathology of cerebral cavernous malformations, may predict subsequent clinically relevant disease activity.

Methods and Results:

Plasma biomarkers were assessed in nonfasting peripheral venous blood collected from consecutive cerebral cavernous malformation subjects followed for 1 year after initial sample collection. A first cohort (N=49) was used to define the best model of biomarker level combinations to predict a subsequent symptomatic lesional hemorrhagic expansion within a year after the blood sample. We generated the receiver operating characteristic curves and area under the curve for each biomarker individually and each weighted linear combination of relevant biomarkers. The best model to predict lesional activity was selected as that minimizing the Akaike information criterion. In this cohort, 11 subjects experienced symptomatic lesional hemorrhagic expansion (5 bleeds and 10 lesional growths) within a year after the blood draw. Subjects had lower soluble CD14 (cluster of differentiation 14;
P
=0.05), IL (interleukin)-6 (
P
=0.04), and VEGF (vascular endothelial growth factor;
P
=0.0003) levels along with higher plasma levels of IL-1β (
P
=0.008) and soluble ROBO4 (roundabout guidance receptor 4;
P
=0.03). Among the 31 weighted linear combinations of these 5 biomarkers, the best model (with the lowest Akaike information criterion value, 25.3) was the weighted linear combination including soluble CD14, IL-1β, VEGF, and soluble ROBO4, predicting a symptomatic hemorrhagic expansion with a sensitivity of 86% and specificity of 88% (area under the curve, 0.90;
P
<0.0001). We then validated our best model in the second sequential independent cohort (N=28).

Conclusions:

This is the first study reporting a predictive association between plasma biomarkers and subsequent cerebral cavernous malformation disease clinical activity. This may be applied in clinical prognostication and stratification of cases in clinical trials.
Clinical Characteristics, Sex Differences, and Outcomes in Patients With Normal or Near‐Normal Coronary Arteries, Non‐Obstructive or Obstructive Coronary Artery Disease
Authors: Ouellette Michelle L. , Löffler Adrián I. , Beller George A. , Workman Virginia K. , Holland Eric , Bourque Jamieson M.
Published: May 2018

Background

Normal or near‐normal coronary arteries (
NNCAs
) or nonobstructive coronary artery disease (
CAD)
are found on invasive coronary angiography in ≈55% of patients. Some attribute this to frequent referral of low‐risk patients. We sought to identify the referral indications, pretest risk, key clinical characteristics, sex, and outcomes in patients with
NNCAs
and nonobstructive
CAD
versus obstructive
CAD
on nonemergent invasive coronary angiography.

Methods and Results

Over 24 months, 925 consecutive patients were classified as having
NNCAs
(≤20% stenosis), nonobstructive
CAD
(21–49% stenosis), or obstructive
CAD
(≥50% stenosis). Outcomes included cardiac death, nonfatal myocardial infarction
,
and late revasclarization.
NNCAs
were found in 285 patients (31.0%), nonobstructive
CAD
in 125 (13.5%), and obstructive
CAD
in 513 (55.5%).
NNCAs
or nonobstructive
CAD
was found in 40.5% with stress ischemia, 27.9% after a non‐ST‐elevation myocardial infarction, and in 55.5% with stable or unstable angina. More women than men (53.5% versus 37.2%;
P
<0.001) had
NNCAs
or nonobstructive
CAD
across all referral indications. Pretest risk was high and
ICA
appropriate in 75.5% and 99.2% of patients, respectively. Annual rates of cardiac death or nonfatal
myocardial infarction
were 1.0%, 1.1%, and 6.7%, respectively, for patients with
NNCAs
, nonobstructive
CAD
, and obstructive
CAD
(
P
<0.001). No sex differences in outcomes were observed with either
NNCAs
, nonobstructive
CAD,
or obstructive
CAD
(
P
=0.84).

Conclusions

Many (44.5%) patients undergoing nonemergent invasive coronary angiography have
NNCAs
or nonobstructive
CAD
despite high pretest risk, including ischemia and troponin elevation. Although women had more
NNCAs
or nonobstructive
CAD
, there were no differences in event rates by sex. Patients with
NNCAs
and nonobstructive
CAD
had very low event rates.
Gene Transfer of Engineered Calmodulin Alleviates Ventricular Arrhythmias in a Calsequestrin‐Associated Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Liu Bin , Walton Shane D. , Ho Hsiang‐Ting , Belevych Andriy E. , Tikunova Svetlana B. , Bonilla Ingrid , Shettigar Vikram , Knollmann Bjorn C. , Priori Silvia G. , Volpe Pompeo , Radwański Przemysław B. , Davis Jonathan P. , Györke Sándor
Published: May 2018

Background

Catecholaminergic polymorphic ventricular tachycardia (
CPVT
) is a familial arrhythmogenic syndrome characterized by sudden death. There are several genetic forms of
CPVT
associated with mutations in genes encoding the cardiac ryanodine receptor (RyR2) and its auxiliary proteins including calsequestrin (
CASQ
2) and calmodulin (CaM). It has been suggested that impairment of the ability of RyR2 to stay closed (ie, refractory) during diastole may be a common mechanism for these diseases. Here, we explore the possibility of engineering CaM variants that normalize abbreviated RyR2 refractoriness for subsequent viral‐mediated delivery to alleviate arrhythmias in non–CaM‐related
CPVT
.

Methods and Results

To that end, we have designed a CaM protein (
GSH
‐M37Q; dubbed as therapeutic CaM or T‐CaM) that exhibited a slowed N‐terminal Ca dissociation rate and prolonged RyR2 refractoriness in permeabilized myocytes derived from
CPVT
mice carrying the
CASQ
2 mutation R33Q. This T‐CaM was introduced to the heart of R33Q mice through recombinant adeno‐associated viral vector serotype 9. Eight weeks postinfection, we performed confocal microscopy to assess Ca handling and recorded surface ECGs to assess susceptibility to arrhythmias in vivo. During catecholamine stimulation with isoproterenol, T‐CaM reduced isoproterenol‐promoted diastolic Ca waves in isolated
CPVT
cardiomyocytes. Importantly, T‐CaM exposure abolished ventricular tachycardia in
CPVT
mice challenged with catecholamines.

Conclusions

Our results suggest that gene transfer of T‐CaM by adeno‐associated viral vector serotype 9 improves myocyte Ca handling and alleviates arrhythmias in a calsequestrin‐associated
CPVT
model, thus supporting the potential of a CaM‐based antiarrhythmic approach as a therapeutic avenue for genetically distinct forms of
CPVT
.
Association of Blood Pressure With Short- and Long-Term Functional Outcome After Stroke Thrombectomy
Authors: Schönenberger Silvia , Uhlmann Lorenz , Ungerer Matthias , Pfaff Johannes , Nagel Simon , Klose Christina , Bendszus Martin , Wick Wolfgang , Ringleb Peter A. , Kieser Meinhard , Möhlenbruch Markus A. , Bösel Julian
Published: May 2018

Background and Purpose—

Outcome after mechanical thrombectomy for ischemic stroke may be influenced by blood pressure (BP). This study aims to assess the association of BP changes during general anesthesia versus conscious sedation with functional outcome after mechanical thrombectomy.

Methods—

SIESTA (Sedation vs Intubation for Endovascular Stroke Treatment) was a monocentric randomized trial of general anesthesia versus conscious sedation during mechanical thrombectomy involving BP target protocols. In this post hoc analysis, BP measurements were divided into 4 phases: preintervention, prerecanalization, postrecanalization, and postintervention. We examined the association between BP and functional outcomes (defined by improvement of 24-hour National Institutes of Health Stroke Scale [NIHSS] and 3-month modified Rankin Scale).

Results—

We found no association between the difference in systolic BP, diastolic BP, and mean arterial pressure from baseline to the different phases of intervention and NIHSS change after 24 hours. Only baseline diastolic BP was associated with a reduced improvement in NIHSS (β=0.17,
P
<0.01). There was no association of BP drops with a change in modified Rankin Scale at 3 months. About sedation, only baseline mean arterial pressure preintervention revealed significant associations (β=0.16,
P
<0.01) with less change in 24-hour NIHSS in conscious sedation group. Otherwise, there was no association for differences of any of the BP measurements with a change in 24-hour NIHSS and long-term functional outcome either in general anesthesia or the conscious sedation group when analyzed separately, consistent with our findings in the entire cohort. Doses of propofol (β=0.84,
P
=0.04) and norepinephrine (β=1.87,
P
=0.01) administered during intervention before recanalization were associated with reduced improvement of NIHSS at 24 hours.

Conclusions—

In a setting, where both sedation regimes general anesthesia and conscious sedation were performed according to strict protocols directed at avoiding BP extremes, our findings suggest that peri-interventional BP drops were not associated with either early neurological improvement or long-term functional outcome.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02126085.
Prediction of Tissue Outcome and Assessment of Treatment Effect in Acute Ischemic Stroke Using Deep Learning
Authors: Nielsen Anne , Hansen Mikkel Bo , Tietze Anna , Mouridsen Kim
Published: May 2018

Background and Purpose—

Treatment options for patients with acute ischemic stroke depend on the volume of salvageable tissue. This volume assessment is currently based on fixed thresholds and single imagine modalities, limiting accuracy. We wish to develop and validate a predictive model capable of automatically identifying and combining acute imaging features to accurately predict final lesion volume.

Methods—

Using acute magnetic resonance imaging, we developed and trained a deep convolutional neural network (CNN
deep
) to predict final imaging outcome. A total of 222 patients were included, of which 187 were treated with rtPA (recombinant tissue-type plasminogen activator). The performance of CNN
deep
was compared with a shallow CNN based on the perfusion-weighted imaging biomarker Tmax (CNN
Tmax
), a shallow CNN based on a combination of 9 different biomarkers (CNN
shallow
), a generalized linear model, and thresholding of the diffusion-weighted imaging biomarker apparent diffusion coefficient (ADC) at 600×10
−6
mm
2
/s (ADC
thres
). To assess whether CNN
deep
is capable of differentiating outcomes of ±intravenous rtPA, patients not receiving intravenous rtPA were included to train CNN
deep,
−rtpa
to access a treatment effect. The networks’ performances were evaluated using visual inspection, area under the receiver operating characteristic curve (AUC), and contrast.

Results—

CNN
deep
yields significantly better performance in predicting final outcome (AUC=0.88±0.12) than generalized linear model (AUC=0.78±0.12;
P
=0.005), CNN
Tmax
(AUC=0.72±0.14;
P
<0.003), and ADC
thres
(AUC=0.66±0.13;
P
<0.0001) and a substantially better performance than CNN
shallow
(AUC=0.85±0.11;
P
=0.063). Measured by contrast, CNN
deep
improves the predictions significantly, showing superiority to all other methods (
P
≤0.003). CNN
deep
also seems to be able to differentiate outcomes based on treatment strategy with the volume of final infarct being significantly different (
P
=0.048).

Conclusions—

The considerable prediction improvement accuracy over current state of the art increases the potential for automated decision support in providing recommendations for personalized treatment plans.