bluuebunny/crossref_metadata_2025 huggingface dataset:
Lumacaftor (VX-809) restores the ability of CF macrophages to phagocytose and kill Pseudomonas aeruginosa
Authors: Barnaby Roxanna , Koeppen Katja , Nymon Amanda , Hampton Thomas H. , Berwin Brent , Ashare Alix , Stanton Bruce A.
Published: November 2017

Cystic fibrosis (CF), the most common lethal genetic disease in Caucasians, is characterized by chronic bacterial lung infection and excessive inflammation, which lead to progressive loss of lung function and premature death. Although ivacaftor (VX-770) alone and ivacaftor in combination with lumacaftor (VX-809) improve lung function in CF patients with the Gly551Asp and del508Phe mutations, respectively, the effects of these drugs on the function of human CF macrophages are unknown. Thus studies were conducted to examine the effects of lumacaftor alone and lumacaftor in combination with ivacaftor (i.e., ORKAMBI) on the ability of human CF ( del508Phe/ del508Phe) monocyte-derived macrophages (MDMs) to phagocytose and kill Pseudomonas aeruginosa. Lumacaftor alone restored the ability of CF MDMs to phagocytose and kill P. aeruginosa to levels observed in MDMs obtained from non-CF (WT-CFTR) donors. This effect contrasts with the partial (~15%) correction of del508Phe Cl− secretion of airway epithelial cells by lumacaftor. Ivacaftor reduced the ability of lumacaftor to stimulate phagocytosis and killing of P. aeruginosa. Lumacaftor had no effect on P. aeruginosa-stimulated cytokine secretion by CF MDMs. Ivacaftor (5 µM) alone and ivacaftor in combination with lumacaftor reduced secretion of several proinflammatory cytokines. The clinical efficacy of ORKAMBI may be related in part to the ability of lumacaftor to stimulate phagocytosis and killing of P. aeruginosa by macrophages.
Subacute Right Ventricular Perforation by Pacemaker Lead Causing Left-Sided Hemothorax and Epicardial Hematoma
Authors: Ahmed Abdelrahman , Shokr Mohamed , Lieberman Randy
Published: November 2017

We report a case of right ventricular wall perforation by a pacemaker lead in a 78-year-old female 18 days after a permanent pacemaker insertion. This injury necessitated explant of the perforating lead and implantation of a new one with surgical backup. We review the literature and discuss the possible risk and protective factors including lead models that were associated with higher incidence of perforation. We review the traditional pacing parameters and their lack of reliability to diagnose perforation and the need for low threshold to utilize imaging in appropriate clinical scenarios. The authors believe this case is of educational value to all health care professionals, especially emergency medicine and internal medicine residents, who routinely see patients with pacemakers complaining of chest pain, shortness of breath, or dizziness.
Analytical Analysis on Nonlinear Parametric Vibration of an Axially Moving String with Fractional Viscoelastic Damping
Authors: Li Ying , Tang Ye
Published: November 2017

The nonlinear parametric vibration of an axially moving string made by rubber‐like materials is studied in the paper. The fractional viscoelastic model is used to describe the damping of the string. Then, a new nonlinear fractional mathematical model governing transverse motion of the string is derived based on Newton’s second law, the Euler beam theory, and the Lagrangian strain. Taking into consideration the fractional calculus law of Riemann‐Liouville form, the principal parametric resonance is analytically investigated via applying the direct multiscale method. Numerical results are presented to show the influences of the fractional order, the stiffness constant, the viscosity coefficient, and the axial‐speed fluctuation amplitude on steady‐state responses. It is noticeable that the amplitudes and existing intervals of steady‐state responses predicted by Kirchhoff’s fractional material model are much larger than those predicted by Mote’s fractional material model.
Guiding Inspiratory Flow: Development of the In-Check DIAL G16, a Tool for Improving Inhaler Technique
Authors: Sanders Mark Jeremy
Published: November 2017

Portable inhalers are divisible into those that deliver medication by patient triggering (pMDIs: a gentle slow inhalation) and those that use the patient’s inspiratory effort as the force for deaggregation and delivery (DPIs: a stronger deeper inspiratory effort). Patient confusion and poor technique are commonplace. The use of training tools has become standard practice, and unique amongst these is an inspiratory flow meter (In-Check) which is able to simulate the resistance characteristics of different inhalers and, thereby, guide the patient to the correct effort. In-Check’s origins lie in the 1960s peak expiratory flow meters, the development of the Mini-Wright peak flow meter, and inspiratory flow assessment via the nose during the 1970s–1980s. The current device (In-Check DIAL G16) is the third iteration of the original 1998 training tool, with detailed and ongoing assessments of all common inhaler resistances (including combination and breath-actuated inhaler types) summarised into resistance ranges that are preset within the device. The device works by interpolating one of six ranges with the inspiratory effort. Use of the tool has been shown to be contributory to significant improvements in asthma care and control, and it is being advocated for assessment and training in irreversible lung disease.
Stimulation of Alpha7 Nicotinic Acetylcholine Receptor Attenuates Nicotine-Induced Upregulation of MMP, MCP-1, and RANTES through Modulating ERK1/2/AP-1 Signaling Pathway in RAW264.7 and MOVAS Cells
Authors: Liu Liping , Wu Hongxian , Cao Qunan , Guo Zhenzhen , Ren Anmin , Dai Qiuyan
Published: November 2017

Vagus nerve stimulation through alpha7 nicotine acetylcholine receptors (α7-nAChR) signaling had been demonstrated attenuation of inflammation. This study aimed to determine whether PNU-282987, a selective α7-nAChR agonist, affected activities of matrix metalloproteinase (MMP) and inflammatory cytokines in nicotine-treatment RAW264.7 and MOVAS cells and to assess the underlying molecular mechanisms. RAW264.7 and MOVAS cells were treated with nicotine at different concentrations (0, 1, 10, and 100 ng/ml) for 0–120 min. Nicotine markedly stimulated the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) and c-Jun in RAW264.7 cells. Pretreatment with U0126 significantly suppressed phosphorylation of ERK1/2 and further attenuated nicotine-induced activation of c-Jun and upregulation of MMP-2, MMP-9, monocyte chemotactic protein- (MCP-) 1, and regulated upon activation normal T cell expressed and secreted (RANTES). Similarly, nicotine treatment also increased phosphorylation of c-Jun and expressions of MMP-2, MMP-9, MCP-1, and RANTES in MOVAS cells. When cells were pretreated with PNU-282987, nicotine-induced activations of ERK1/2 and c-Jun in RAW264.7 cells and c-Jun in MOVAS cells were effectively inhibited. Furthermore, nicotine-induced secretions of MMP-2, MMP-9, MCP-1, and RANTES were remarkably downregulated. Treatment with α7-nAChR agonist inhibits nicotine-induced upregulation of MMP and inflammatory cytokines through modulating ERK1/2/AP-1 signaling in RAW264.7 cells and AP-1 in MOVAS cells, providing a new therapeutic for abdominal aortic aneurysm.
The Use of Adenosine to Enable Safe Implantation of Transcatheter Tricuspid Valve
Authors: Zeniou Vicki , Chen Shmuel , Shuvy Mony , Luria David , Lotan Chaim , Danenberg Haim D.
Published: November 2017

High precision is necessary during percutaneous transcatheter heart valve implantation. The precision of the implantation has been established by increasing the heart rate (usually to 200 beats per minute) to the point of significantly reduced cardiac output and thus minimizing valve movement. Routinely, this tachycardia is induced by rapid pacing. Here we report a case of failure to pace during valve-in-valve (VIV) Edwards Sapien XT implantation in the tricuspid valve position. Transient cardiac arrest was induced by intravenous adenosine injection enabling accurate valve implantation.
Identification of Sensory Processing and Integration Symptom Clusters: A Preliminary Study
Authors: Miller Lucy Jane , Schoen Sarah A. , Mulligan Shelley , Sullivan Jillian
Published: November 2017

Rationale. This study explored subtypes of sensory processing disorder (SPD) by examining the clinical presentations of cluster groups that emerged from scores of children with SPD on the Sensory Processing 3-Dimension (SP-3D) Inventory. Method. A nonexperimental design was used involving data extraction from the records of 252 children with SPD. Exploratory cluster analyses were conducted with scores from the SP-3D Inventory which measures sensory overresponsivity (SOR), sensory underresponsivity (SUR), sensory craving (SC), postural disorder, dyspraxia, and sensory discrimination. Scores related to adaptive behavior, social-emotional functioning, and attention among children with different sensory modulation patterns were then examined and compared. Results. Three distinct cluster groups emerged from the data: High SOR only, High SUR with SOR, and High SC with SOR. All groups showed low performance within multiple domains of adaptive behavior. Atypical behaviors associated with social-emotional functioning and attention varied among the groups. Implications. The SP-3D Inventory shows promise as a tool for assisting in identifying patterns of sensory dysfunction and for guiding intervention. Better characterization can guide intervention precision and facilitate homogenous samples for research.
Solving Fixed‐Point Problems with Inequality and Equality Constraints via a Non‐Interior Point Homotopy Path‐Following Method
Authors: Su Menglong , Shang Yufeng
Published: November 2017

In recent years, fixed‐point theorems have attracted increasing attention and have been widely investigated by many authors. Moreover, determining a fixed point has become an interesting topic. In this paper, we provide a constructive proof of the general Brouwer fixed‐point theorem and then obtain the existence of a smooth path which connects a given point to the fixed point. We also present a non‐interior point homotopy algorithm for solving fixed‐point problems on a class of nonconvex sets by numerically tricking this homotopy path.
Optimized Size and Tab Width in Partial Solar Cell Modules including Shingled Designs
Authors: Roeth Julius , Facchini Arrigo , Bernhard Norbert
Published: November 2017

Cell-to-module loss (CTM loss) is defined by optical and electrical losses. Using partial solar cells can reduce ohmic losses. Today, some manufactures use halved cells even if they have to employ extra effort for sorting, placing, and soldering the solar cells. In this work, the advantage of partial solar cells is described. An LTSpice simulation is used to quantify the reduced ohmic loss and the resulting efficiency gain for differently separated solar cells. This efficiency gain is compared with the whole module area caused by the tab and cell areas. The additional gain due to the backsheet reflection is added afterwards. It can be pointed out that the use of half cells is a technical optimal application while not using shingled modules.
Anatomical Basis of the Myofascial Trigger Points of the Gluteus Maximus Muscle
Authors: Akamatsu Flavia Emi , Yendo Tatiana Mina , Rhode Ciro , Itezerote Ana Maria , Hojaij Flávio , Andrade Mauro , Hsing Wu Tu , Jacomo Alfredo Luiz
Published: November 2017

Myofascial pain syndrome is characterized by pain and limited range of motion in joints and caused by muscular contracture related to dysfunctional motor end plates and myofascial trigger points (MTrPs). We aimed to observe the anatomical correlation between the clinically described MTrPs and the entry point of the branches of the inferior gluteal nerve into the gluteus maximus muscle. We dissected twenty gluteus maximus muscles from 10 human adult cadavers (5 males and 5 females). We measured the muscles and compiled the distribution of the nerve branches into each of the quadrants of the muscle. Statistical analysis was performed by using Student’s t-test and Kruskal-Wallis tests. Although no difference was observed either for muscle measurements or for distribution of nerve branching among the subjects, the topography of MTrPs matched the anatomical location of the entry points into the muscle. Thus, anatomical substract of the MTrPs may be useful for a better understanding of the physiopathology of these disorders and provide basis for their surgical and clinical treatment.
The Propagation of Thermoelastic Waves in Anisotropic Media of Orthorhombic, Hexagonal, and Tetragonal Syngonies
Authors: Ispulov Nurlybek A. , Qadir Abdul , Zhukenov Marat , Arinov Erkin
Published: November 2017

The investigation of wave propagation in elastic medium with thermomechanical effects is bound to have important economic implications in the field of composite materials, seismology, geophysics, and so on. In this article, thermoelastic wave propagation in anisotropic mediums of orthorhombic and hexagonal syngony having heterogeneity along z-axis is studied. Such medium has second-order axis symmetry. By using analytical matriciant method, a set of equations of motions in thermoelastic medium are reduced to an equivalent set of the first-order differential equations. In the general case, for the given set of equations, structures of fundamental solutions are made and dispersion relations are obtained.
Inflammatory Fibroid Polyp: An Unusual Cause of Ileoileal Intussusception
Authors: Adams Haley S. , Bergstrom Brian , Haines Bret , Roberts Nathan
Published: November 2017

Inflammatory fibroid polyp (IFP), or Vanek’s tumor, is a rare benign lesion of the gastrointestinal tract. Clinical manifestations of IFP vary based on size and location within the GI tract. This case describes a patient who presented with hematochezia and abdominal pain. Computed tomography revealed ileoileal intussusception without a clear lead point. The patient underwent resection of the intussuscepted small bowel with primary anastomosis. A large polypoid mass was identified as the pathological lead point. Histopathological and immunohistochemical analysis revealed an IFP. Review of the literature indicates that early surgical intervention is the treatment of choice for intussusception caused by IFP. Lesions are typically reported as solitary, and resection is curative.
Kerosene Oil Poisoning among Children in Rural Sri Lanka
Authors: Dayasiri M. B. Kavinda Chandimal , Jayamanne Shaluka F. , Jayasinghe Chamilka Y.
Published: November 2017

Introduction. Kerosene oil poisoning is one of common presentations to emergency departments among children in rural territories of developing countries. This study aimed to describe clinical manifestations, reasons for delayed presentations, harmful first aid practices, complications, and risk factors related to kerosene oil poisoning among children in rural Sri Lanka. Methods. This multicenter study was conducted in North-Central province of Sri Lanka involving all in-patient children with acute kerosene oil poisoning. Data were collected over seven years from thirty-six hospitals in the province. Data collection was done by pretested, multistructured questionnaires and a qualitative study. Results. Male children accounted for 189 (60.4%) while 283 (93%) children were below five years. The majority of parents belonged to farming community. Most children ingested kerosene oil in home kitchen. Mortality rate was 0.3%. Lack of transport facilities and financial resources were common reasons for delayed management. Hospital transfer rate was 65.5%. Thirty percent of caregivers practiced harmful first aid measures. Commonest complication was chemical pneumonitis. Strongest risk factors for kerosene oil poisoning were unsafe storage, inadequate supervision, and inadequate house space. Conclusions. Effect of safe storage and community education in reducing the burden of kerosene oil poisoning should be evaluated. Since many risk factors interact to bring about the event of poisoning in a child, holistic approaches to community education in rural settings are recommended.
Path Planning and Vehicle Scheduling Optimization for Logistic Distribution of Hazardous Materials in Full Container Load
Authors: Chai Huo , He Ruichun , Ma Changxi , Dai Cunjie , Zhou Kun
Published: November 2017

Mathematical models for path planning and vehicle scheduling for logistic distribution of hazardous materials in full container load (FCL) are established, with their problem-solving methods proposed. First, a two-stage multiobjective optimization algorithm is designed for path planning. In the first stage, pulse algorithm is used to obtain the Pareto paths from the distribution center to each destination. In the second stage, a multiobjective optimization method based on Nondominated Sorting Genetic Algorithm II (NSGA-II) is designed to obtain candidate transport paths. Second, with analysis on the operating process of vehicles with hazardous materials in FCL, the vehicle scheduling problem is converted to Vehicle Routing Problem with Time Windows (VRPTW). A problem-solving method based on estimation of distribution is adopted. A transport timetable for all vehicles based on their transport paths is calculated, with participation of the decision-makers. A visual vehicle scheduling plan is presented for the decision-makers. Last, two examples are used to test the method proposed in this study: distribution of hazardous materials in a small-scale test network and distribution of oil products for sixteen gas stations in the main districts of Lanzhou city. In both examples, our method is used to obtain the path selection and vehicle scheduling plan, proving that validity of our method is verified.
Characterization of SGN-CD123A, A Potent CD123-Directed Antibody–Drug Conjugate for Acute Myeloid Leukemia
Authors: Li Fu , Sutherland May Kung , Yu Changpu , Walter Roland B. , Westendorf Lori , Valliere-Douglass John , Pan Lucy , Cronkite Ashley , Sussman Django , Klussman Kerry , Ulrich Michelle , Anderson Martha E. , Stone Ivan J. , Zeng Weiping , Jonas Mechthild , Lewis Timothy S. , Goswami Maitrayee , Wang Sa A. , Senter Peter D. , Law Che-Leung , Feldman Eric J. , Benjamin Dennis R.
Published: November 2017

Treatment choices for acute myelogenous leukemia (AML) patients resistant to conventional chemotherapies are limited and novel therapeutic agents are needed. IL3 receptor alpha (IL3Rα, or CD123) is expressed on the majority of AML blasts, and there is evidence that its expression is increased on leukemic relative to normal hematopoietic stem cells, which makes it an attractive target for antibody-based therapy. Here, we report the generation and preclinical characterization of SGN-CD123A, an antibody–drug conjugate using the pyrrolobenzodiazepine dimer (PBD) linker and a humanized CD123 antibody with engineered cysteines for site-specific conjugation. Mechanistically, SGN-CD123A induces activation of DNA damage response pathways, cell-cycle changes, and apoptosis in AML cells. In vitro, SGN-CD123A–mediated potent cytotoxicity of 11/12 CD123+ AML cell lines and 20/23 primary samples from AML patients, including those with unfavorable cytogenetic profiles or FLT3 mutations. In vivo, SGN-CD123A treatment led to AML eradication in a disseminated disease model, remission in a subcutaneous xenograft model, and significant growth delay in a multidrug resistance xenograft model. Moreover, SGN-CD123A also resulted in durable complete remission of a patient-derived xenograft AML model. When combined with a FLT3 inhibitor quizartinib, SGN-CD123A enhanced the activity of quizartinib against two FLT3-mutated xenograft models. Overall, these data demonstrate that SGN-CD123A is a potent antileukemic agent, supporting an ongoing trial to evaluate its safety and efficacy in AML patients (NCT02848248). Mol Cancer Ther; 17(2); 554–64. ©2017 AACR.
Peripartum Haemorrhage: Haemostatic Aspects of the New German PPH Guideline
Authors: Lier Heiko , von Heymann Christian , Korte Wolfgang , Schlembach Dietmar ,   for the German PPH Guideline Group
Published: November 2017

Peripartum haemorrhage remains one of the main causes of maternal mortality world-wide. The German, Austrian and Swiss Societies of Gynaecology and Obstetrics have updated the current guidelines for the treatment of peripartum haemorrhage together with the German Society of Anaesthesiology and Intensive Care Medicine and the Society of Thrombosis and Haemostasis Research. The recommendations have been the result of a thorough review of the available scientific literature and a consensus process involving all members of the guideline group. A key element of the anaesthesiological and haemostatic management is the development of a multidisciplinary standard operating procedure combining surgical as well as medical and haemostatic treatments depending on the severity of bleeding. The guideline underscores the value of clinical and laboratory diagnostics of peripartum haemorrhage as early as possible, even pre-emptively. This allows for an early identification of causes of bleeding and a specific treatment. The guideline comprises evidence-based recommendations for the use of uterotonics, tranexamic acid and blood products such as factor concentrates, fresh frozen plasma, platelet concentrates, packed red blood cells, recombinant activated factor VII and desmopressin. In addition, recommendations for blood conservation strategies involving the use of cell salvage, permissive hypotension and transfusion triggers are given.
Recommendations for Endovascular Care of Stroke Patients
Authors: Hill Michelle , Glenn Brenda A. , Reese Brenda J. , Morrow Benjamin
Published: November 2017

The field of neurointerventional radiology (NIR) therapy, including acute ischemic stroke intervention, endovascular intracranial aneurysm management, and treatment of intra- and extracranial large-vessel disease, has evolved over the past 18 years. To support this specialized advanced care requires nursing standards of care for staff to provide direct patient care in NIR suites and intensive management of this high-risk patient population. The intent of this paper is to provide a complementary document for the Stroke Interventional Laboratory Consensus (SILC) statement that will specifically address the nursing standards of care for patients in an NIR suite.
Metachronous and Synchronous Occurrence of 5 Primary Malignancies in a Female Patient between 1997 and 2013: A Case Report with Germline and Somatic Genetic Analysis
Authors: Nyqvist Jenny , Persson Fredrik , Parris Toshima Z. , Helou Khalil , Kenne Sarenmalm Elisabeth , Einbeigi Zakaria , Borg Åke , Karlsson Per , Kovács Anikó
Published: November 2017

The number of patients with multiple primary malignancies has been increasing steadily in recent years. In the present study, we describe a unique case of an 81-year-old woman with 5 metachronous and synchronous primary malignant neoplasms. The patient was first diagnosed with an endometrium adenocarcinoma in 1997 and a colon adenocarcinoma in 2002. Eleven years after her colon surgery, in 2013, the patient presented with 3 other primary malignancies within a 4-month time span: an invasive malignant melanoma on the lower leg, an invasive mucinous breast carcinoma in the right breast, and a pleomorphic spindle cell sarcoma on the left upper arm. Subsequent routine medical checkups in 2013–2017 revealed no metastases of the primary malignancies. The patient mentioned a familial aggregation of malignant tumors, including 2 sisters with breast cancer and a brother with lung cancer. Interestingly, next-generation sequencing analysis of the patient’s blood sample detected no mutations in the BRCA1, BRCA2, TP53, PTEN, CDH1, PALB2, RAD51C, RAD51D, MLH1, MSH2, MSH6, PMS2, EPCAM, APC, MUTYH, STK11, BMPR1A, SMAD4, PTEN, POLE, POLD1, GREM1, and GALNT12 genes. Therefore, whole genome sequencing is warranted to identify cancer-related genetic alterations in this patient with quintuple primary malignancies.
Metachronous Development of Meningothelial Meningioma, Basal Cell Carcinoma, and Glioblastoma Multiforme in a Patient with Pancreatic Incidentaloma
Authors: Naydenov Emanuil , Bussarsky Venceslav , Angelov Kostadin , Penkov Marin , Nachev Sevdalin , Hadjidekova Savina , Toncheva Draga
Published: November 2017

We report the unique case of a 61-year-old male patient with known pancreatic incidentaloma who additionally developed 3 other histologically different tumors: left sphenoid wing meningothelial meningioma, basal cell carcinoma of the occiput, and right occipital lobe glioblastoma multiforme. The latter were totally removed with a favorable clinical outcome. The patient’s family history was unremarkable, and no data on any previous head and neck irradiation were found.
Determinants, Prevalence, and Trajectory of Long-Term Post-Stroke Cognitive Impairment: Results from a 4-Year Follow-Up of the ARCOS-IV Study
Authors: Mahon Susan , Parmar Priya , Barker-Collo Suzanne , Krishnamurthi Rita , Jones Kelly , Theadom Alice , Feigin Valery
Published: November 2017

Background: The long-term (>12 months) prevalence, predictors, and trajectory of post-stroke cognitive deficits are not well established, especially at a community level. This study investigated the longitudinal course and prevalence of cognitive impairment in an incidence cohort, identifying factors associated with declining cognition. Methods: Two hundred fifty-seven participants (mean age = 67.93 ± 13.59) of first-ever stroke survivors, completed cognitive assessments within 2 weeks post stroke, and/or 1, 6, 12, and 48-month. Multivariate linear and logistic models were used to identify baseline predictors (reported as OR with 95% CI) and trajectory of cognitive impairment. Results: Cognitive functioning significantly declined by 2.8 points by 4 years post stroke. Eighty-four percent of stroke survivors had cognitive impairment indicative of post-stroke dementia (mean Montreal cognitive assessment = 20 ± 4.7) at 4-year. There were significant as­sociations between progressive cognitive decline and the ­following factors: male gender (OR 2.9, 95% CI 1.6–5.9, ­p = 0.0171), coronary artery disease (OR 2.96, 95% CI 1.35–6.49, p = 0.0070), arrhythmia (OR 2.21, 95% CI 1.07–4.57, p = 0.0317), not in a relationship (OR 2.8, 95% CI 1.4–5.50, p < 0.0001), and not employed (OR 4.9, 95% CI 1.9–12.1, p < 0.0001). Conclusions: Cognitive deficits remain highly prevalent at 4-year post stroke. Early identification of those at higher risk of declining cognition is vital to target rehabilitation interventions at the acute stage and improve overall outcomes.
Inflammatory and Angiogenic Factors Linked to Longitudinal Microvascular Changes in Hemodialysis Patients Irrespective of Treatment Dose Intensity
Authors: Mitsides Nicos , Cornelis Tom , Broers Natascha J.H. , Diederen Nanada M.P. , Brenchley Paul , Heitink-ter Braak Nicole  , van der Sande Frank M. , Schalkwijk Casper G. , Kooman Jeroen P. , Mitra Sandip
Published: November 2017

Background: Cardiovascular disease is a major contributor to the poor outcomes observed in hemodialysis. We investigated the relationship between hemodialysis intensity and vascular parameters in high-dose (HDHD; >12hrs/week) and Conventional (CHD; ≤12hrs/week) hemodialysis intensity over a 6-month period. Methods: We present the 6-month longitudinal analysis of a 2-year multicenter study investigating the effects of HDHD on cardiovascular parameters. We used pulse wave velocity, 24hr ambulatory blood pressure and sublingual dark field capillaroscopy measurements to assess macro- and microcirculation on 6-monthly basis. Pro-inflammatory and endothelial biomarkers were also measured at 6-monthly intervals. Results: 47 participants (21 HDHD, 26 CHD) were studied. CHD were older (63.5±14.2 vs 53.7±12.6 yr; p=0.018), with shorter dialysis vintage (median 23 vs 61 months; p=0.001). There was considerable variability in the degree and direction of change of circulatory measurements over a 6-month period. Hemodialysis intensity (hrs/week) did not correlate to these changes, when adjusted for age, dialysis vintage and comorbidity. Higher levels of Interleukin (IL)-8 measured at baseline independently predicted an increase in the Perfused Boundary Region (5-25μm) of the endothelial glycocalyx (p=0.010) whilst higher levels of soluble Flt-1 had a significant inverse effect (p=0.002) in an adjusted linear model. Conclusion: Hemodialysis intensity did not predict changes in either macro- or microvascular parameters. Inflammation mediated through the IL-8 pathway predicted microvascular injury while Flt-1, a potential marker of angiogenesis and endothelial repair, might have a significant protective role. Further understanding of these pathways will be necessary to improve dialysis outcomes.
AQP2 Abundance is Regulated by the E3-Ligase CHIP Via HSP70
Authors: Centrone Mariangela , Ranieri Marianna , Di Mise Annarita Di , Berlingerio Sante Princiero , Russo Annamaria , Deen Peter M.T. , Staub Olivier , Valenti Giovanna , Tamma Grazia
Published: November 2017

Background/Aims: AQP2 expression is mainly controlled by vasopressin-dependent changes in protein abundance which is in turn regulated by AQP2 ubiquitylation and degradation, however the proteins involved in these processes are largely unknown. Here, we investigated the potential role of the CHIP E3 ligase in AQP2 regulation. Methods: MCD4 cells and kidney slices were used to study the involvement of the E3 ligase CHIP on AQP2 protein abundance by cell homogenization and immunoprecipitation followed by immunoblotting. Results: We found that AQP2 complexes with CHIP in renal tissue. Expression of CHIP increased proteasomal degradation of AQP2 and HSP70 abundance, a molecular signature of HSP90 inhibition. Increased HSP70 level, secondary to CHIP expression, promoted ERK signaling resulting in increased AQP2 phosphorylation at S261. Phosphorylation of AQP2 at S256 and T269 were instead downregulated. Next, we investigated HSP70 interaction with AQP2, which is important for endocytosis. Compared with AQP2-wt, HSP70 binding decreased in AQP2-S256D and AQP2-S256D-S261D, while increased in AQP2-S256D-S261A. Surprisingly, expression of CHIP-delUbox, displaying a loss of E3 ligase activity, still induced AQP2 degradation, indicating that CHIP does not ubiquitylate and degrade AQP2 itself. Conversely, the AQP2 half-life was increased upon the expression of CHIP-delTPR a domain which binds Hsc70/HSP70 and HSP90. HSP70 has been reported to bind other E3 ligases such as MDM2. Notably, we found that co-expression of CHIP and MDM2 increased AQP2 degradation, whereas co-expression of CHIP with MDM2-delRING, an inactive form of MDM2, impaired AQP2 degradation. Conclusion: Our findings indicate CHIP as a master regulator of AQP2 degradation via HSP70 that has dual functions: (1) as chaperone for AQP2 and (2) as an anchoring protein for MDM2 E3 ligase, which is likely to be involved in AQP2 degradation.
Deficiency of Functional Iron-Sulfur Domains in ABCE1 Inhibits the Proliferation and Migration of Lung Adenocarcinomas By Regulating the Biogenesis of Beta-Actin In Vitro
Authors: Yu Qian , Han Xu , Tian Da-Li
Published: November 2017

Background/Aims: ATP-binding cassette transporter E1 (ABCE1), a unique ABC superfamily member that bears two Fe-S clusters, is essential for metastatic progression in lung cancer. Fe-S clusters within ABCE1 are crucial for ribosome dissociation and translation reinitiation; however, whether these clusters promote tumor proliferation and migration is unclear. Methods: The interaction between ABCE1 and β-actin was confirmed using GST pull-down. The lung adenocarcinoma (LUAD) cell line A549 was transduced with lentiviral packaging vectors overexpressing either wild-type ABCE1 or ABCE1 with Fe-S cluster deletions (ΔABCE1). The role of Fe-S clusters in the viability and migration of cancer cells was evaluated using clonogenic, MTT, Transwell and wound healing assays. Cytoskeletal rearrangement was determined using immunofluorescent techniques. Results: Fe-S clusters were the key domains in ABCE1 involved in binding to β-actin. The proliferative and migratory capacity increased in cells overexpressing ABCE1. However, the absence of Fe-S clusters reversed these effects. A549 cells overexpressing ABCE1 exhibited irregular morphology and increased levels of cytoskeletal polymerization as indicated by the immunofluorescence images. In contrast, cells expressing the Fe-S cluster deletion mutant presented opposing effects. Conclusion: These results demonstrate the indispensable role of Fe-S clusters when ABCE1 participates in the proliferation and migration of LUADs by interacting with β-actin. The Fe-S clusters of ABCE1 may be potential targets for the prevention of lung cancer metastasis.
LncRna CPS1-IT1 Suppresses Cell Proliferation, Invasion and Metastasis in Colorectal Cancer
Authors: Zhang Wei , Yuan Weitang , Song Junmin , Wang Shijun , Gu Xiaoming
Published: November 2017

Background/Aims: Increasing evidence demonstrates that long non-coding RNAs (lncRNAs) regulate diverse cellular processes and cancer progression. Whether lncRNAs play any functional role in colorectal carcinoma (CRC) remains largely unknown. The aim of this study was to investigate the role of lncRNA CPS1 intronic transcript 1 (CPS1-IT1) in CRC. Methods: Expression of CPS1-IT1 was initially assessed in human CRC tissues and in a series of CRC cell lines. The correlations between CPS1-IT1 levels and survival outcomes were analyzed to elucidate the clinical significance of CPS1-IT1 in CRC. The underlying mechanisms of CPS1-IT1 in CRC were analyzed through in vitro and in vivo functional assays. Results: Expression of CPS1-IT1 was significantly decreased in CRC tissues and cell lines, and patients with low CPS1-IT1 expression had poor survival outcomes. The results of in vitro assays revealed that CPS1-IT1 significantly reduced cell proliferation, migration and invasion capacities and accelerated cell apoptosis, thereby suppressing epithelial-mesenchymal transition (EMT). An in vivo animal model also demonstrated the tumor-suppressive role of CPS1-IT1. Conclusion: In this study, we found that CPS1-IT1 has a tumor-suppressive role in CRC. Our data suggest that CPS1-IT1 could be used as a new prognostic biomarker and therapeutic target for CRC.
Huaier Extract Inhibits Breast Cancer Progression Through a LncRNA-H19/MiR-675-5p Pathway
Authors: Wang Jijun , Wang Xiaolong , Chen Tong , Jiang Liyu , Yang Qifeng
Published: November 2017

Background/Aims: Increasing evidence indicates that Huaier extract has promising therapeutic effects against cancer. However, the mechanisms that underlie its anti-tumor effects remain unclear. In recent years, various studies have shown that long noncoding RNAs (lncRNAs) play a critical role in the regulation of cancer development and progression. Here, we explored the role of lncRNAs in Huaier-induced tumor suppression. Methods: Microarray profiling was performed to identify the candidate lncRNAs affected by Huaier extract. Quantitative realtime PCR (qPCR) was used to evaluate the transfection efficiency and the influence of Huaier extract on H19 expression. The effect of Huaier extract on the cell viability was examined by MTT. Moreover, the rates of apoptotic cells were detected using flow-cytometric analysis. Western blot analysis was applied to show the protein levels of CBL. Results: Microarray data derived from Huaier-treated breast cancer cells identified H19 as a potential target. Huaier extract reduced the expression of H19. The over-expression of H19 inhibited the cytotoxic effects of Huaier extract; in contrast, reduced H19 expression enhanced the function of Huaier extract. MiR-675-5p was identified as a mature product of H19. Moreover, Huaier extract reduced the miR-675-5p expression. Upregulating miR-675-5p reversed the inhibitory effects of Huaier extract, whereas downregulating miR-675-5p sensitized breast cancer cells to the effect of Huaier extract. In addition, Huaier extract increased the expression of CBL protein, a direct target of miR-675-5p. Conclusion: Collectively, the data demonstrate that Huaier extract reduces viability and induces apoptosis in breast cancer cells via H19-miR-675-5p-CBL axis regulation.
Contemporary science education and challenges in the presente society: perspectives in physics teaching and learning
Authors: Leite Cristina
Published: November 2017

A obra, publicação da Faculdade de Educação da Universidade de São Paulo, discute vários aspectos do ensino de Física que estiveram na pauta da conferência "Educação de ciência contemporânea e desafios na sociedade atual: perspectivas no ensino e aprendizagem da Física". A conferência partiu dos trabalhos selecionados e apresentados no 2º WCPE - Conferência Internacional realizada em São Paulo, de 11 a 15 de julho de 2017. ​O evento, realizado a cada quatro anos, tem como objetivo os estudos e as apresentações das pesquisas sobre o tema, estimulando o desenvolvimento de planos de ação que fortaleçam o ensino e a aprendizagem de Física em todos os níveis e em muitos países.
Sobre os aspectos clínicos e a complexidade do trabalho: as clínicas do trabalho compreendidas pela perspectiva da Psicossociologia
Authors: Casadore Marcos Mariani
Published: November 2017

O surgimento das denominadas “Clínicas do Trabalho” como um agrupamento de campos metodológicos – evidenciados por uma perspectiva clínica de análise da complexidade das relações de trabalho e de compreensão da interação entre questões subjetivas e organizacionais do trabalho – aponta também para a leitura “ampliada” e multifacetada inerente à psicologia do trabalho atual. Embora não constituam uma escola única de pensamento, as Clínicas do Trabalho compartilham posicionamentos críticos frente às problemáticas que envolvem a intricada relação entre subjetividade e trabalho, tendo como principais interesses suas dimensões simbólicas e culturais, inerentes às vinculações interpessoais, e a questão da atividade no trabalho (i.e., ação e poder de ação do sujeito na situação de trabalho). A pesquisa, que atrela os recortes social e clínico, extrapola a definição mais técnica ou formal de trabalho, emprestando a ela a ideia de implicação subjetiva bem como de construção de significados e sentidos protagonizados pelo sujeito em situação, considerado essencialmente em sua dimensão histórica e como ator social; suas propostas de intervenção vêm conjuntamente, nesta mesma perspectiva, e buscam a construção de um saber inerente à realidade do trabalho, inseparável da experiência de onde emerge e dos sujeitos que a constroem – pautando tal compreensão justamente pela complexidade da situação, junto de seus conflitos, dificuldades e questionamentos. Neste artigo, buscamos discutir algumas características fundamentais desta perspectiva metodológica voltada às questões do trabalho a partir das contribuições da Psicossociologia francesa.
Narrar para conhecer os modos de ser-trabalhar-existir: o (difícil) cenário do trabalho contemporâneo
Authors: Duarte Daniele Almeida
Published: November 2017

Neste texto, recorremos aos campos discursivos que possibilitam vislumbrar quem é o sujeito e seu entorno, sendo contribuintes dessa discussão os pressupostos da Saúde Coletiva e a Psicossociologia, para debater o complexo cenário do trabalho contemporâneo. Com o intuito de desvendar os modos de ser-trabalhar-existir, que conjugam o socius e a subjetividade, propomos a narrativa como dispositivo capaz de evidenciar a complexidade deste fenômeno. Essas referências teórico-conceituais permitem ao pesquisador, profissionais de saúde e diferentes atores sociais identificar o que no trabalho atenta contra o corpo, como também o que afeta a subjetividade, logo, que modos de existência são forjados no campo singular e social. Nesta perspectiva, temos como desafio (re)conhecer a trabalhadora e o trabalhador como sujeitos de saberes que, ao assumirem sua voz e protagonismo, podem conferir meios para transformação laboral e social.
A degeneração dos espaços públicos e a supervalorização narcísica como facetas do mal-estar no trabalho
Authors: Shiozaki Marcos Paulo , Hashimoto Francisco
Published: November 2017

Em alguns espaços, o modelo de trabalho está se caracterizando de maneira diferente nos tempos atuais quando comparado com aquela forma taylorista que ainda predomina em muitas organizações, com a clássica figura centralizada no chefe e nas metas. Justamente devido a essas mudanças, esse novo modelo apresenta uma boa notoriedade por se centrar no indivíduo e por uma proposta de uma suposta liberdade dentro de ambientes laborais, onde não existem metas e a figura do chefe é dissolvida. É possível perceber que essa supervalorização no indivíduo cria espaços cada vez mais particulares e individualistas, na mesma medida em que existe uma diminuição do investimento de lugares que prezam a coletividade. Diante disso, o objetivo deste escrito é analisar como a degeneração dos espaços públicos e a supervalorização narcísica se apresentam como fatores de mal-estar no trabalho. Para realizar este estudo, foram utilizadas algumas obras psicanalíticas freudianas e balintianas, além do aporte dos autores da Psicossociologia. Assim, defende-se aqui que o declínio dos espaços públicos e a exacerbação narcísica, tão relacionada ao trabalho, levam cada vez mais dificuldades aos indivíduos em encontrarem espaços efetivos de satisfação pulsional.
Correlação entre independência funcional e cognição em homens com AVC
Authors: Caro Camila Caminha , Cruz Daniel Marinho Cezar
Published: November 2017

O acidente vascular cerebral é uma doença crônica que causa sequelas motoras e cognitivas e possíveis alterações na capacidade funcional. Este estudo objetivou identificar os níveis de independência funcional e cognição em homens com acidente vascular cerebral e verificar a presença de correlações entre essas variáveis. Para tanto, adotou-se um estudo transversal descritivo-correlacional com amostra de conveniência composta por trinta (n=30) homens adultos. Para a coleta de dados foram aplicados a Medida de Independência Funcional e o Mini Exame do Estado Mental. Para a análise dos dados adotou-se a análise descritiva simples e o coeficiente de correlação de Pearson. Os resultados demonstraram o predomínio de sujeitos dependentes e com altos índices de alterações cognitivas bem como correlações positivas fortes entre a cognição e a independência motora (r=0,827 p=0,000), cognitiva (r=0,912 p=0,000) e total (r=0,882 p=0,000). Esses dados demonstram o impacto das alterações cognitivas na independência funcional de sujeitos pós-AVC e sugerem a necessidade de intervenções específicas em terapia ocupacional destinadas a esses.
Atenção domiciliar no âmbito da reabilitação e prática centrada na família: aproximando teorias para potencializar resultados
Authors: Dias Jane Fonseca , Grossi Julia Baldoni , Costa Luciana Assis , Furtado Sheyla Rossana Cavalcanti , Mancini Marisa Cotta , Sampaio Rosana Ferreira
Published: November 2017

Estudo de revisão narrativa que apresenta e discute os pressupostos da Prática Centrada na Família (PCF) e as influências desta abordagem no contexto da Atenção Domiciliar (AD) no âmbito da reabilitação no Sistema Único de Saúde (SUS). Com base nas informações obtidas, a AD e a PCF foram analisadas, permitindo discutir o potencial impacto dos pressupostos da PCF na AD, do sistema publico de saúde brasileiro. A AD tem importante papel na constituição de redes substitutivas, produzindo novos modos de cuidar. Entretanto, alguns problemas na organização deste serviço geram descontinuidade do cuidado, sobrecarga de todos os níveis de atenção e dificultam o vínculo entre profissionais/usuário/família. A PCF propõe que os programas domiciliares sejam direcionados aos familiares, especialmente aos cuidadores, para que estes desenvolvam as competências necessárias para a prestação do cuidado, possibilitando assim assistência integral, contextualizada e humanizada ao usuário. A utilização da PCF no contexto da AD no SUS, tendo em conta o empoderamento do usuário e sua família, pode favorecer o estabelecimento de vínculos afetivos e de co--responsabilidade entre profissionais/usuário/família, impactando na qualidade da assistência prestada e nos resultados esperados.
Papéis ocupacionais de indivíduos com anemia falciforme
Authors: Cunha José Henrique Da Silva , Monteiro Claudia Franco , Ferreira Lúcia Aparecida , Cordeiro Júnia Rjeille , Souza Laís Madalena De Paula
Published: November 2017

A anemia falciforme pode afetar o desempenho dos papéis ocupacionais do indivíduo devido à crise vaso-oclusiva dolorosa e internações frequentes. O objetivo deste estudo foi verificar quais papéis ocupacionais estão sendo menos desempenhados no presente; o porquê estão sendo menos desempenhados; e identificar o grau de importância de cada papel ocupacional com menor desempenho para a vida de pessoas com anemia falciforme, que são atendidas no Hemocentro de Uberaba/Fundação Hemominas. Nesta pesquisa participaram 30 pessoas com anemia falciforme. Os dados foram coletados por meio do formulário do instrumento Lista de Identificação de Papéis Ocupacionais e, para maior compreensão desses dados obtidos pelo mesmo, utilizou-se a metodologia do grupo focal. Os resultados demonstraram que os papéis menos desempenhados no presente foram os de religioso, estudante, trabalhador, voluntário e participante em organizações. Já os papéis mais importantes no presente foram: estudante, cuidador, trabalhador, voluntário e passatempo/amador. Conclui-se que as ocupações do tempo presente dos indivíduos entrevistados estão bastante afetadas em função das condições clínicas impostas pela anemia falciforme, tais como os papéis de estudante e de trabalhador, já que a maioria eram adultos jovens.
Crioterapia moderada: uma alternativa no tratamento da lesão celular induzida pelo exercício
Authors: Costa Manoel Da Cunha , Perrier-Melo Raphael José , Brito-Gomes Jorge Luiz de , Tashiro Tetsuo , Soares José Manuel Costa
Published: November 2017

Objetivo: analisar o efeito da crioterapia moderada com imersão (15º celsius - C), nas respostas inflamatórias musculares, nas variáveis bioquímicas e neuromotoras após uma sessão de exercício de força excêntrico. Procedimentos Metodológicos: 18 homens (18-25 anos) saudáveis, não praticantes de exercício físico e que participaram voluntariamente da pesquisa foram recrutados. Inicialmente foram randomizados em três grupos: Grupo Controle (GC), Grupo Exercício (GE) e Grupo Exercício + Crioterapia (EX + CT). Após a aleatorização, os voluntários seguiram para realização de testes: a) bioquímico (Creatina Quinase - CK), b) neuromotor (amplitude de movimento - ÂNGULO), c) escala de dor - DOR e d) um teste de força isométrica máxima. Em seguida, os grupos experimentais realizaram séries de ações excêntricas máximas para região anterior e posterior da perna no exercício sentadinha. Após a sessão analisou-se CK, ÂNGULO e DOR, nos momentos 24, 48, 72, 96 e 120 horas. Os sujeitos do EX + CT receberam tratamento crioterápico imediatamente após a sessão e nos momentos 12, 24, 36 e 48 horas subsequentes. Resultados: Em comparação com o repouso, os valores de CK, DOR e ÂNGULO apresentaram aumento significativo após as sessões nos grupos experimentais. O GE exibiu valores significativamente superior ao EX + CT em todas as variáveis analisadas. Conclusão: A crioterapia mostrou-se uma alternativa viável no tratamento da miopatia do exercício e da dor muscular tardia.