bluuebunny/crossref_metadata_2025 huggingface dataset:
Actions developed by the Brazilian Physiological Society to promote women’s participation in science
Authors: Mello-Carpes Pâmela B. , Abreu Alice Rangel de Paiva , Staniscuaski Fernanda , Souza Mauren Assis , Campagnole-Santos Maria Jose , Irigoyen Maria Cláudia
Published: April 2019

Here we described two activities related to Women in Science: one main conference and one symposium, both developed during the Annual Congress of the Brazilian Physiological Society, which were held within the XXXIII Annual Meeting of the Federation of Brazilian Experimental Biology Societies, from September 3–6, 2018, in Campos do Jordão (SP/Brazil). This conference and the symposium were among the most popular activities of the congress. This is important because the activities addressed important issues, including the fact that only 29% of the worlds’ researchers are women, and women have difficulty progressing in a scientific career. Our report discusses why and which strategies could change this reality. We believe this symposium has not only contributed to advance and bring insights to physiological sciences, but, more importantly, it inspired and motivated physiologists to think about gender balance and the contribution and participation of women in physiological science.
Antiapoptotic and mitochondrial biogenetic effects of exercise training on ovariectomized hypertensive rat hearts
Authors: Lin Yi-Yuan , Hong Yi , Yu Shao-Hong , Wu Xu-Bo , Shyu Woei-Cherng , Chen Jwo-Sheng , Ting Hua , Yang Ai-Lun , Lee Shin-Da
Published: April 2019

This study was to investigate the effects of exercise training on antiapoptotic pathways and mitochondrial biogenesis in ovariectomized hypertensive rats. Histopathological analysis, TUNEL assay, and Western blotting were performed on the excised hearts from female spontaneously hypertensive rats (SHR), which were divided into a sham-operated sedentary hypertensive (SHR-S), a sedentary hypertensive ovariectomized (SHR-O), and hypertensive ovariectomized rats that underwent treadmill exercise training (SHR-OT; 60 min/day, 5 days/wk) for 8 wk, along with normotensive Wistar Kyoto rats (WKY). When compared with the WKY group, the SHR-S group exhibited decreased protein levels of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and mitochondrial OPA-1 (mitochondrial biogenesis) and decreased further in the SHR-O group. The protein levels of p-PI3K, p-Akt, Bcl-2, Bcl-xL (prosurvival pathways), and the protein levels of PGC-1α and mitochondrial OPA1 (mitochondrial biogenesis) were increased in the SHR-OT group, but estrogen receptor (ER)α and ERβ were not changed when compared with the SHR-O group. The protein levels of t-Bid, Bad, Bax, cytosolic cytochrome c, activated caspase 9, and activated caspase 3 (mitochondria-dependent apoptotic pathways), as well as Fas ligand, TNF-α, Fas receptors, Fas-associated death domain, activated caspase 8 (Fas receptor-dependent apoptotic pathways) were decreased in the SHR-OT group, when compared with the SHR-O group. Exercise training protection on the coexistence of hypertension and ovariectomy-induced cardiac mitochondria-dependent and Fas receptor-dependent apoptotic pathways by enhancing the Bcl2-related and mitochondrial biogenetic prosurvival pathways might provide a new therapeutic effect on cardiac protection in oophorectomized early postmenopausal hypertensive women.

NEW & NOTEWORTHY Widely dispersed cardiac apoptosis was found in the coexistence of hypertension and ovariectomy. Exercise training on a treadmill could prevent ovariectomized hypertension-induced widely dispersed cardiac apoptosis via mitochondria-dependent apoptotic pathway (t-Bid, Bad, Bax, cytosolic cytochrome c, activated caspase 9, and activated caspase 3) and Fas receptor-dependent apoptotic pathway (Fas ligand, tumor necrosis factor-α, Fas receptors, Fas-associated death domain, activated caspase 8, and activated caspase 3) through enhancing the Bcl2-related (p-PI3K, p-Akt, Bcl-2, Bcl-xL) and mitochondrial biogenetic (PGC-1α and mitochondrial optic atrophy 1) prosurvival pathways.
Evaluation of Basalt Fibers on Wind Turbine Blades through Finite Element Analysis
Authors: García V. , Vargas L. , Acuña A. , Sosa J. B. , Durazo E. , Ballesteros R. , Ocampo J.
Published: April 2019

Here we use finite element analysis to determine the suitability of basalt fiber as a substitute for E-glass in structural applications, which would improve the cost effectiveness of small wind turbine blades. Five NACA (National Advisory Committee for Aeronautics) profiles were evaluated to select the optimum shape for the wind operation conditions. To obtain the wind load pressure distribution over the blade, a computational aerodynamic analysis by CFD (computational fluid dynamics) was performed based on the blade’s design and operating conditions. Material properties and mechanical tests were carried out to obtain the fiber volume fraction, density, Young’s modulus, shear modulus, and Poisson relation of polymeric matrix composites made using basalt and fiberglass. The obtained wind loads and material properties were used on a FEM (finite element model) analysis to evaluate the structural behavior of the blade under normal and critical operating conditions. Both fibers meet the structural requirements under normal operating conditions. We detected a reduction of 4% in the blade stress when basalt fibers are used instead of glass fibers, and a reduction of 68% in the total deformation for a critical load case of 40 m/s was obtained when using basalt fibers, which met the structural requirements and maximum power generation required for this wind turbine design.
Evaluation of the Effect of Repeated Intravitreal Bevacizumab Injections on the Macular Microvasculature of a Diabetic Patient Using Optical Coherence Tomography Angiography
Authors: Elnahry Ayman G. , Abdel-Kader Ahmed A. , Raafat Karim A. , Elrakhawy Khaled
Published: April 2019

A 53-year-old female patient with center-involving diabetic macular edema affecting the left eye was imaged using optical coherence tomography angiography (OCTA) in both eyes. She underwent three monthly intravitreal bevacizumab injections in the left eye only and OCTA was repeated in both eyes one month following the last injection and showed decreased vascular density (VD) in the treated left eye but not in the untreated right eye compared to baseline. No further injections were required in either eye, and OCTA was done in both eyes 4 months following the last injection which showed improved VD of the left eye with stable VD in the right. Three monthly intravitreal bevacizumab injections were then required in both eyes; then OCTA was repeated following the last injection and revealed decreased VD in both eyes compared to previous scan. OCTA could be a useful tool for detecting VD changes following bevacizumab injections in diabetics.
Analysis of Longitudinal Mechanical Properties of Buried Suspended Pipeline Resisting Collapse
Authors: Lin Yujian , Lv Yanping , Liu Xu , Chen Fuquan
Published: April 2019

Ground subsidence caused by collapse leads to suspension or subsidence of the pipe, resulting in the stress concentration. It is a significant factor being a threat to safe operation of the pipeline. Based on Pasternak’s beam‐on‐elastic‐foundation theory, this study presents a mechanical model of interaction between the buried suspended pipeline and the soil, which considers the effect of the beam width. The pipeline was modeled as a buried part and a suspended part. According to the compatibility conditions of suspended and nonsuspended parts, this paper solved differential equations describing the deflection of pipeline and derived the formulas of deflection and internal force. This solution involves whole cases of the Pasternak model. Connecting to the pipeline operation status, the formulas of piping stress were deduced by piping stress analysis. Meanwhile, piping stress analysis can define the scope of application of the model. Compared with the measured values and results of the Winkler model, the calculated results of the Pasternak model are more accurate and suitable for predicting the behavior of the pipeline in the limit state. In addition, according to normalized analysis of main affecting factors which comprise the pipe material, pipe dimension, pipe depth, and length of collapse, it was also found that the length of collapse dominates the stability of the pipeline.
Efficacy and Safety of Chinese Herbs for the Prevention of the Risk of Renal Damage in Henoch-Schonlein Purpura in Children: Meta-Analysis of Randomized Controlled Trials and GRADE Evaluation
Authors: Li Bing , Yang Meng , He Gai-Li , Gao Xu-Guang , Li Le , Zhai Wen-Sheng
Published: April 2019

Objective. To evaluate the efficacy and safety of traditional Chinese medicine in preventing kidney damage caused by Henoch-Schonlein Purpura (HSP) in Children by meta-analysis. Methods. We systematically searched the main Chinese and English electronic databases and collected randomized controlled trials of Chinese herbs in children with HSP until July 2018. Then we used the bias risk assessment tool in Cochrane Handbook 5. 1. 0 to complete the risk assessment of the included studies. We utilized STATA12.0 and RevMan 5.3 for meta-analysis and GRADE pro. for quality evaluation of evidence. Result. (1) Meta-analysis: data from 39 studies, representing 3643 individuals, were included in the analysis. Thirty-seven studies were treated with traditional Chinese medicine for clearing away heat and cooling blood, which were combined. On this basis, subgroup analysis was conducted according to the bias risk of the original study. It showed that Chinese herbs can significantly improve the treatment effect (OR: 4.31, 95% CI [3.34, 5.57], P < 0.01) and reduce the risk of renal damage (RR: 0.36; 95% CI [0.21, 0.61], P < 0.01) and the risk of recurrence (RR: 0.43, 95% CI [0.34, 0.54], P<0.01). (2) Side effect: a total of 7 studies described adverse reactions, and 12 of 319 patients in therapy group had adverse events and 20 of 263 patients in control group. (3) Publication bias: the bias risk Egger’s test for the incidence of kidney injury was P=0.572, the relapse rate Egger’s test was P=0.175, the efficiency was combined with the low-risk original study, and the bias risk Egger’s test was P=0.175. There was not any significant publication bias based on the funnel plot and Egger’s test. (4) GRADE evaluation: GRADE evaluation showed that the quality of evidence in the risk of renal damage and recurrence rate was moderate. Conclusion. Chinese medicine treatment can prevent the occurrence of renal damage in children with HSP and can reduce the recurrence rate, the incidence of adverse reactions, and the effect in terms of efficiency. However, the quality of the included studies in the meta-analysis and the quality of the evidence of outcomes were not high; the clinical use of the evidence needs to be cautious.
Cladophialophora bantianaCerebral Phaeohyphomycosis Complicated by Pulmonary Nocardiosis: A Tale of Two Infections
Authors: Khaliq Muhammad Farhan , Ihle Rayan E. , Schirtzinger Christopher P.
Published: April 2019

Cladophialophora bantiana, a melanized neurotropic fungus, is the most commonly reported agent of cerebral phaeohyphomycosis. We present a case of cerebral phaeohyphomycosis due toC. bantianawith a concomitantNocardiainfection in the lung. The patient was a 64-year-old male who presented with one-week history of productive cough, confusion, and staggering gait. Brain MRI showed multiple enhancing masses, and chest CT demonstrated multifocal consolidation. To confirm diagnosis, brain biopsy was performed that showedCladophialophora bantiana. Bronchoscopic lung biopsy confirmed infection withNocardia araoensis. The patient was treated with trimethoprim-sulfamethoxazole, meropenem, voriconazole, and liposomal amphotericin in addition to partial resection of the brain mass. After several weeks in the hospital and deteriorating status with poor prognosis, medical care was withdrawn.Cladophialophora bantianainfection is rare and requires multidisciplinary approach for accurate diagnostic confirmation. Aggressive and long-term treatment with voriconazole along with early neurosurgical intervention may offer an improved chance of survival in these patients.
Hericium erinaceus Improves Mood and Sleep Disorders in Patients Affected by Overweight or Obesity: Could Circulating Pro-BDNF and BDNF Be Potential Biomarkers?
Authors: Vigna Luisella , Morelli Federica , Agnelli Gianna M. , Napolitano Filomena , Ratto Daniela , Occhinegro Alessandra , Di Iorio Carmine , Savino Elena , Girometta Carolina , Brandalise Federico , Rossi Paola
Published: April 2019

Epidemiological data indicate that subjects affected by obesity have an increased risk of developing mood disorders. The relationship between obesity and mood disorders is bidirectional. We assessed whether a Hericium erinaceus treatment improved depression, anxiety, sleep, and binge eating disorders after 8 weeks of supplementation in subjects affected by overweight or obesity under a low calorie diet regimen. Looking for a possible clinical biomarker, we assessed the serum balance between brain-derived neurotrophic factor (BDNF) and its precursor pro-BDNF before and after H. erinaceus supplementation. Seventy-seven volunteers affected by overweight or obesity were recruited at the offices of the Department of Preventive Medicine, Luigi Devoto Clinic of Work, Obesity Centre, at the IRCCS Foundation Policlinico Hospital of Milan (Italy). Patients were recruited only if they had a mood and/or sleep disorder and/or were binge eating as evaluated through self-assessment questionnaires. We used two different enzyme-linked immunosorbent assays kits to discriminate circulating levels of pro-BDNF and BDNF. Eight weeks of oral H. erinaceus supplementation decreased depression, anxiety, and sleep disorders. H. erinaceus supplementation improved mood disorders of a depressive-anxious nature and the quality of the nocturnal rest. H. erinaceus increased circulating pro-BDNF levels without any significant change in BDNF circulating levels.
Cardiac Metastasis in a Patient with Head and Neck Cancer: A Case Report and Review of the Literature
Authors: Kim Joseph K. , Sindhu Kunal , Bakst Richard L.
Published: April 2019

Cardiac metastasis from a primary head and neck cancer is a rare finding. Most patients with cardiac metastases have nonspecific symptoms that may vary depending on the severity and location of the lesion. Due to the infrequency of reported cases, there are no clear guidelines for the diagnosis or management of cardiac metastasis in head and neck cancer patients. In this report, we discuss the case of a patient with a primary diagnosis of oral tongue cancer who developed a cardiac metastasis that was detected antemortem.
Gastrointestinal Beriberi and Wernicke’s Encephalopathy Triggered by One Session of Heavy Drinking
Authors: Tjong Elysia , Peng Yen-Yi
Published: April 2019

An otherwise healthy 30-year-old male acquired gastrointestinal beriberi and subsequent Wernicke’s encephalopathy after 1 session of heavy drinking. Nausea, vomiting, and anorexia relentlessly progressed. The patient developed external ophthalmoplegia after 2 months. Intravenous 1,000 mg thiamine reversed both neurologic and gastrointestinal symptoms within hours. It is hard to diagnose gastrointestinal beriberi since the symptoms are nonspecific. The patient underwent 11 emergency room visits, 3 hospital admissions, and laparoscopic cystectomy within 2 months, but the gastrointestinal symptoms continued to progress. Two months after the onset of gastrointestinal symptoms, external ophthalmoplegia appeared, and, therefore, intravenous thiamine was given. The simultaneous resolution of the debilitating gastrointestinal symptoms and external ophthalmoplegia was unique. Thiamine deficiency remains underdiagnosed and should be considered in patients who develop unexplained gastroparesis or autonomic nervous failure of the digestive system, even in the nonalcoholic population.
Endothelial-Specific Deficiency of ATG5 (Autophagy Protein 5) Attenuates Ischemia-Related Angiogenesis
Authors: Sprott David , Poitz David M. , Korovina Irina , Ziogas Athanasios , Phieler Julia , Chatzigeorgiou Antonios , Mitroulis Ioannis , Deussen Andreas , Chavakis Triantafyllos , Klotzsche-von Ameln Anne
Published: April 2019

Objective—

Pathological angiogenesis, such as exuberant retinal neovascularization during proliferative retinopathies, involves endothelial responses to ischemia/hypoxia and oxidative stress. Autophagy is a clearance system enabling bulk degradation of intracellular components and is implicated in cellular adaptation to stressful conditions. Here, we addressed the role of the ATG5 (autophagy-related protein 5) in endothelial cells in the context of pathological ischemia-related neovascularization in the murine model of retinopathy of prematurity.

Approach and Results—

Autophagic vesicles accumulated in neovascular tufts of the retina of retinopathy of prematurity mice. Endothelium-specific
Atg5
deletion reduced pathological neovascularization in the retinopathy of prematurity model. In contrast, no alterations in physiological retina vascularization were observed in endothelial-specific ATG5 deficiency, suggesting a specific role of endothelial ATG5 in pathological hypoxia/reoxygenation–related angiogenesis. Consistently, in an aortic ring angiogenesis assay, endothelial ATG5 deficiency resulted in impaired angiogenesis under hypoxia/reoxygenation conditions. As compared to ATG5-sufficient endothelial cells, ATG5-deficient cells displayed impaired mitochondrial respiratory activity, diminished production of mitochondrial reactive oxygen species and decreased phosphorylation of the VEGFR2 (vascular endothelial growth factor receptor 2). Consistently, ATG5-deficient endothelial cells displayed decreased oxidative inactivation of PTPs (phospho-tyrosine phosphatases), likely due to the reduced reactive oxygen species levels resulting from ATG5 deficiency.

Conclusions—

Our data suggest that endothelial ATG5 supports mitochondrial function and proangiogenic signaling in endothelial cells in the context of pathological hypoxia/reoxygenation–related neovascularization. Endothelial ATG5, therefore, represents a potential target for the treatment of pathological neovascularization-associated diseases, such as retinopathies.
Uncoupling Protein 2 Increases Blood Pressure in DJ‐1 Knockout Mice
Authors: De Miguel Carmen , Hamrick William C. , Sedaka Randee , Jagarlamudi Sudha , Asico Laureano D. , Jose Pedro A. , Cuevas Santiago
Published: April 2019

Background

The redox‐sensitive chaperone
DJ
‐1 and uncoupling protein 2 are protective against mitochondrial oxidative stress. We previously reported that renal‐selective depletion and germline deletion of

DJ
‐1

increases blood pressure in mice. This study aimed to determine the mechanisms involved in the oxidative stress–mediated hypertension in

DJ
‐1

−/−

mice.

Methods and Results

There were no differences in sodium excretion, renal renin expression, renal
NADPH
oxidase activity, and serum creatinine levels between

DJ
‐1

−/−

and wild‐type mice. Renal expression of nitro‐tyrosine, malondialdehyde, and urinary kidney injury marker‐1 were increased in

DJ
‐1

−/−

mice relative to wild‐type littermates.
mRNA
expression of mitochondrial heat shock protein 60 was also elevated in kidneys from

DJ
‐1

−/−

mice, indicating the presence of oxidative stress. Tempol‐treated

DJ
‐1

−/−

mice presented higher serum nitrite/nitrate levels than vehicle‐treated

DJ
‐1

−/−

mice, suggesting a role of the
NO
system in the high blood pressure of this model. Tempol treatment normalized renal kidney injury marker‐1 and malondialdehyde expression as well as blood pressure in

DJ
‐1

−/−

mice, but had no effect in wild‐type mice. The renal
Ucp2
mRNA
expression was increased in

DJ
‐1

−/−

mice versus wild‐type and was also normalized by tempol. The renal‐selective silencing of
Ucp2
led to normalization of blood pressure and serum nitrite/nitrate ratio in

DJ
‐1

−/−

mice.

Conclusions

The deletion of

DJ
‐1

leads to oxidative stress–induced hypertension associated with downregulation of
NO
function, and overexpression of
Ucp2
in the kidney increases blood pressure in

DJ
‐1

−/−

mice. To our knowledge, this is the first report providing evidence of the role of uncoupling protein 2 in blood pressure regulation.
GILE: A Generalized Input-Label Embedding for Text Classification
Authors: Pappas Nikolaos , Henderson James
Published: April 2019

Neural text classification models typically treat output labels as categorical variables that lack description and semantics. This forces their parametrization to be dependent on the label set size, and, hence, they are unable to scale to large label sets and generalize to unseen ones. Existing joint input-label text models overcome these issues by exploiting label descriptions, but they are unable to capture complex label relationships, have rigid parametrization, and their gains on unseen labels happen often at the expense of weak performance on the labels seen during training. In this paper, we propose a new input-label model that generalizes over previous such models, addresses their limitations, and does not compromise performance on seen labels. The model consists of a joint nonlinear input-label embedding with controllable capacity and a joint-space-dependent classification unit that is trained with cross-entropy loss to optimize classification performance. We evaluate models on full-resource and low- or zero-resource text classification of multilingual news and biomedical text with a large label set. Our model outperforms monolingual and multilingual models that do not leverage label semantics and previous joint input-label space models in both scenarios.
Autosegmental Input Strictly Local Functions
Authors: Chandlee Jane , Jardine Adam
Published: April 2019

Autosegmental representations (ARs; Goldsmith, 1976 ) are claimed to enable local analyses of otherwise non-local phenomena Odden ( 1994 ). Focusing on the domain of tone, we investigate this ability of ARs using a computationally well-defined notion of locality extended from Chandlee ( 2014 ). The result is a more nuanced understanding of the way in which ARs interact with phonological locality.
Assortments of Digestive Enzymes Induced in First Instar Larvae of Busseola fusca Feeding on Different Plants
Authors: Juma Gérald , Le Ru Bruno , Calatayud Paul-André
Published: April 2019

The stem borer Busseola fusca (Fuller) (Lepidoptera: Noctuidae) is an important pest of maize and sorghum in sub-Saharan Africa. This insect has oligophagous feeding habits, feeding mostly on maize and sorghum with a narrow range of wild Poaceous plant species. We hypothesised that first instar B. fusca larvae, the critical stage for successful establishment on a host plant, can establish and then grow on a particular plant as a result of induction of a complement of digestive enzymes that mediates host acceptance at first instars. A fast semi-quantitative analysis of potentially digestive enzymatic activities present in the first larvae previously fed for 4 days on leaves of host and non-host plants was performed using the API-ZYM kit system able to detect a multiplex of enzyme activities. Regardless of the plant species, the larvae exhibited higher activities of the carbohydrate metabolising enzymes than of aminopeptidases and proteases. In addition, highest activities of carbohydrates degrading enzymes were exhibited by larvae that consumed leaves of the most preferred plant species of B. fusca. Conversely, esterases were only detected in neonate larvae that consumed leaves of the less preferred and non-host plants. No alkaline phosphatase and lipase activities were detected. The significance of these results was discussed in terms of food requirements of first instar larvae when settling on a plant.
IL-25 contributes to lung fibrosis by directly acting on alveolar epithelial cells and fibroblasts
Authors: Xu Xuefeng , Luo Sa , Li Biyun , Dai Huaping , Zhang Jinglan
Published: April 2019

Interleukin (IL)-25 is shown to potentiate type-2 immunity and contribute to chronic airway inflammation and remodeling in allergic airway diseases. However, the role of IL-25 in idiopathic pulmonary fibrosis (IPF), dominated by nonatopic type-2 immunity, still remains largely unclear. Herein, we detected the expression levels of IL-25 and IL-17BR (IL-25’s receptor) by using lung tissue samples gained from IPF patients and normal subjects. Also, by directly intranasal (IN) instillation of IL-25 to mice, we examined the potential roles and mechanisms of IL-25 in the development of lung fibrosis. Furthermore, we tested whether IL-25 can directly activate human lung fibroblast by in vitro cell culture. Immunohistochemical, Western blot, and real-time reverse transcription-polymerase chain reaction (RT-PCR) showed that the mRNA and protein levels of IL-25 and IL-17BR are significantly higher in IPF patients when compared with normal controls. Intranasal instillation of IL-25 to mice markedly induces the expressions of alveolar IL-5 and IL-13. Furthermore, immunohistochemical analysis showed that the main components of the extracellular matrix including collagen I, collagen III and fibronectin are notably induced by IL-25 instillation in lung parenchyma (especially in alveolar epithelial cells [AECs]). Also, IL-25 potentiates the expression of connective tissue growth factor (CTGF) in AECs and the recruitment of lung fibroblast. By using Cell Counting Kit-8 and EDU incorporation assay, we found that IL-25 markedly enhances the proliferation of lung fibroblast. Finally, IL-25 potentiates fibroblast to produce several fibrogenic genes including collagen I/III, fibronectin, CTGF, α smooth muscle (α-SMA) and tissue inhibitor of metalloproteinase (TIMP)-1 as determined by RT-PCR assay. Collectively, we concluded that IL-25 is increased in IPF lungs and contributes to lung fibrosis by directly mediating AECs/fibroblast activation.

Impact statement

Our work focused on alveolar epithelial cells (AECs)-derived type-2 cytokine (interleukin [IL]-25) in the pathogenesis of idiopathic pulmonary fibrosis (IPF). We showed that IL-25 and IL-17BR (IL-25’s receptor) is upregulated in lung tissues (especially in AECs and lung fibroblasts) of IPF patients and contributes to lung fibrosis by directly activating lung fibroblasts and modulating epithelial–mesenchymal transition (EMT) of AECs. We suggest that IL-25 may be one of the master switches hidden in the milieu of abnormal epithelial–mesenchymal crosstalk. Treatment targeting IL-25 may be the potential and novel method for IPF patients.
Pharmacokinetic interaction of riociguat and antiretroviral combination regimens in HIV‐1‐infected adults
Authors: DeJesus Edwin , Saleh Soundos , Cheng Sue , van der Mey Dorina , Becker Corina , Frey Reiner , Unger Sigrun , Mueck Wolfgang
Published: April 2019

Riociguat, a first‐in‐class soluble guanylate cyclase stimulator, is approved for the treatment of pulmonary arterial hypertension (PAH), a serious potential complication of human immunodeficiency virus (HIV) infection. This open‐label study investigated the pharmacokinetic drug–drug interaction potential of antiretroviral therapies on riociguat exposure in HIV‐infected adults. HIV‐infected adults without PAH on stable antiretroviral regimens (efavirenz/emtricitabine/tenofovir disoproxil, emtricitabine/rilpivirine/tenofovir disoproxil, elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil, abacavir/dolutegravir/lamivudine, or a ritonavir‐boosted triple regimen) for ≥ 6 weeks received a single riociguat dose (0.5 mg). Riociguat pharmacokinetics and safety were assessed; pharmacokinetics was compared with historical healthy volunteer data. Of 41 participants treated (n = 8 in each arm, except n = 9 in the ritonavir‐boosted triple regimen arm), 40 were included in the pharmacokinetic analyses. Riociguat median tmax was 1.00–1.27 h, with comparable maximum concentration (Cmax) across the five background antiretroviral groups. Riociguat exposure was highest with abacavir/dolutegravir/lamivudine, followed by elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil > emtricitabine/rilpivirine/tenofovir disoproxil > ritonavir‐boosted triple regimen > efavirenz/emtricitabine/tenofovir disoproxil; riociguat area under the plasma concentration versus time curve (AUC) was approximately threefold higher with abacavir/dolutegravir/lamivudine than efavirenz/emtricitabine/tenofovir disoproxil. Compared with historical data, riociguat exposure in HIV‐infected adults was similar when co‐administered with efavirenz/emtricitabine/tenofovir disoproxil, slightly increased when administered with ritonavir‐boosted triple regimen and increased by approximately threefold when administered with abacavir/dolutegravir/lamivudine. Riociguat was well tolerated, with no new safety findings. Riociguat was well tolerated in adults with HIV on stable background antiretroviral therapy although an apparent increase in AUC of riociguat was observed in patients receiving abacavir/dolutegravir/lamivudine. Patients should be monitored closely during riociguat initiation and dose adjustment for signs and symptoms of hypotension.
Pressure overload induced right ventricular remodeling is not attenuated by the anti‐fibrotic agent pirfenidone
Authors: Andersen Stine , Birkmose Axelsen Julie , Ringgaard Steffen , Randel Nyengaard Jens , Holm Nielsen Signe , Genovese Federica , Asser Karsdal Morten , Adler Hyldebrandt Janus , Brandt Sørensen Charlotte , de Man Frances S. , Jan Bogaard Harm , Erik Nielsen‐Kudsk Jens , Andersen Asger
Published: April 2019

Cardiac fibrosis contributes to the development of heart failure in pulmonary hypertension. We aimed to assess the development of fibrosis and the effects of treatment with the anti‐fibrotic agent pirfenidone in pressure overload induced right ventricular (RV) failure. Wistar rat weanlings were randomized to pulmonary trunk banding (PTB) or sham surgery. One week after the procedure, PTB rats were randomized into two groups with either six weeks on standard chow or treatment with pirfenidone mixed in chow (700 mg/kg/day). RV hemodynamic effects were evaluated by echocardiography, cardiac magnetic resonance imaging (MRI), and pressure‐volume measurements. Sections from the isolated RV, left ventricle, and septum were sampled systematically; stereological point grids and the nucleator were used to estimate volume of fibrosis and cardiac hypertrophy, respectively. PTB caused RV failure in all rats subjected to the procedure. The volume fraction of fibrosis in the RV increased threefold in PTB rats corresponding to a sixfold increase in total volume of RV fibrosis. Volume fraction of fibrosis and total volume of fibrosis also increased in the septum and in the left ventricle. Pirfenidone reduced body weight but did not improve RV hemodynamics or reduce cardiac fibrosis. RV cardiomyocyte profile area was increased twofold in PTB rats without any effect of pirfenidone. RV pressure overload after PTB induced not only RV but also septal and left ventricular fibrosis assessed by stereology. Treatment with pirfenidone reduced body weight but did not reduce the development of cardiac fibrosis or delay the progression of RV failure.
Alterations in Regional Homogeneity in Patients With Unilateral Chronic Tinnitus
Authors: Gentil Anthony , Deverdun Jeremy , Menjot de Champfleur Nicolas , Puel Jean-Luc , Le Bars Emmanuelle , Venail Frédéric
Published: April 2019

Chronic subjective tinnitus is a widespread disorder. This perceptual anomaly is assumed to result from a dysbalance of excitatory and inhibitory mechanisms on different levels of the auditory pathways. However, the brain areas involved are still under discussion. Using resting-state functional magnetic resonance imaging, we investigate differences in cerebral regional homogeneity (ReHo) between patients with unilateral chronic tinnitus and nontinnitus control subjects. To our knowledge, our study is the first to investigate the intraregional connectivity of patients with unilateral tinnitus in relation to hearing loss. Our analyses, based on strict recruitment and characterization of the participants, showed reduced ReHo in the primary auditory cortex contralateral to the side of the perceived tinnitus percept in patients. Reduced ReHo in this same region was also correlated with increased Tinnitus Handicap Inventory and Visual Analogue Scale for loudness scores, reflecting an alteration of synchronization in this region related to the perceived loudness of the tinnitus and the related distress. Furthermore, increased ReHo in the supramarginal and angular gyri ipsilateral to the tinnitus side was correlated with increased tinnitus duration and hearing threshold at the tinnitus pitch. The correlations observed in these brain areas, which are normally related to the nontinnitus ear, could highlight compensatory mechanisms in these secondary auditory regions.
Clinical Impact of Circulating Tumor RAS and BRAF Mutation Dynamics in Patients With Metastatic Colorectal Cancer Treated With First-Line Chemotherapy Plus Anti–Epidermal Growth Factor Receptor Therapy
Authors: Maurel Joan , Alonso Vicente , Escudero Pilar , Fernández-Martos Carlos , Salud Antonieta , Méndez Miguel , Gallego Javier , Rodriguez Jose Ramon , Martín-Richard Marta , Fernández-Plana Julen , Manzano Hermini , Méndez José Carlos , Zanui Montserrat , Falcó Esther , Gil-Raga Mireia , Aparicio Jorge , Feliu Jaime , García-Albéniz Xabier , Torres Ferràn , Rojo Federico , Bellosillo Beatriz , Mendiola Marta , Fernández Veronica , Reig Oscar , Claes Bart , Maertens Geert , Sablon Erwin , Jacobs Bart , Montagut Clara
Published: April 2019

PURPOSE

RAS and BRAF mutations can be detected as a mechanism of acquired resistance in circulating tumor (ct) DNA in patients with metastatic colorectal cancer treated with anti–epidermal growth factor receptor therapy.

METHODS

RAS and BRAF mutational status was assessed in ctDNA in a baseline plasma sample and a serum sample collected at the time of the last available determination (named secondary extraction) from patients with KRAS exon 2 wild-type metastatic colorectal cancer treated in two first-line prospective biomarker-designed clinical trials (PULSE, ClinicalTrials.gov identifier: NCT01288339; and POSIBA, ClincialTrials.gov identifier: NCT01276379).

RESULTS

Analysis of extended RAS and BRAF in tissue and plasma from 178 patients with KRAS exon 2 wild-type metastatic colorectal cancer showed a sensitivity of 64.1% and a specificity of 90%. The median overall survival (OS) of baseline patients with RAS and BRAF mutations in ctDNA was 22.3 months (95% CI, 15.6 to 29 months) and 8.9 months (95% CI, 6.3 to 11.4 months), respectively, which was significantly inferior to the median OS of 40.4 months (95% CI, 35.9 to 44.9 months) in two patients with wild-type disease ( P < .001). Acquisition of RAS/BRAF mutations occurred in nine of 63 patients (14%) with progressive disease (PD; ie, blood draw within 1 month before PD or after PD) compared with six of 73 patients (8%) with no PD or blood extraction for ctDNA analysis before 1 month of PD ( P = .47). Median OS in patients with RAS/BRAF acquisition was 23.9 months (95% CI, 19.7 to 27.9 months) compared with 40.6 months (95% CI, not reached to not reached) in patients who remained free of mutations ( P = .016).

CONCLUSION

Our results confirm that baseline RAS and BRAF testing in ctDNA discriminates survival. The emergence of RAS/BRAF mutations has limited relevance for the time to progression to anti–epidermal growth factor receptor therapy.
‘I felt like I was doing something wrong’: A qualitative exploration of mothers' experiences of breastfeeding
Authors: Jackson Jessica Eve , Hallam Jenny
Published: April 2019

Despite its multiple health benefits, rates of breastfeeding to 2 years and beyond remain low in the UK. This qualitative study explored the experiences of support provided by health professionals to mothers breastfeeding beyond infancy. A key finding of the study was that health services are effective at supporting breastfeeding in the postnatal period, but that beyond the 1-year review the focus shifts to rapid weaning. A new approach to support breastfeeding continuation alongside the introduction of complementary foods is needed in line with professional guidance and recommendations. As critical reflective practitioners, health visitors are ideally placed to support and educate women about the wider social complexities of breastfeeding. However, health service commissioners need to recognise the importance of investment in the profession to enable health visitors to use their skills fully.
El uso de los sujetos pronominales explícitos y nulos por los aprendices de ELE
Authors: Bran Rǎzvan
Published: April 2019

This paper aims to analyse the errors made by Romanian students who learn Spanish as a Foreign Language in using pronominal and null subjects. Neither Romanian (students´ L1) nor Spanish require pro subjects, but after investigating the corpus (including opinion essays and narratives), we have noticed that pronominal subjects are misused. In our view, one possible explanation of this syntactic error could be the interference with other foreign languages that students learn, which are pro-drop languages. This type of error appears more often in the first stage of interlingua and the more advanced the student is, the less errors he makes. As the syntactic competence is fundamental in the acquisition process of the L2, it is very important this phenomenon to be reckoned both by students and by teachers.
Presencia y significación de la muerte en la obra de Gustavo Adolfo Bécquer
Authors: Meza Alegría Gabriel , Montes Brunet Hugo
Published: April 2019

In this paper we trace the presence of death in the works of Gustavo Adolfo Bécquer, identify the way it is manifested through his Rimas and propose a classification of the types of death present in his legends. This is carried out with the aim of understanding the textualization of death in the becquerian works and determine the connections with aspects such as Romanticisms, mystic and spirituality. We propose that death is an essential element in the poetics of the author, which reveals a transcendentalist vision that crosses the main creative aspects of the Spanish poet.
Deshonra (Daniel Tinayre, 1952)
Authors: Gijón Pablo Rubio
Published: April 2019

Within the context of the film industry of the first peronist period (1946-1955) crime films established themselves as a means to disseminate the dominant ideology. Some of the characteristics of this genre were used to leave proof of the pre-eminence of the State as a safeguard of the status quo. However, Deshonra (1952) resorts in its structure to visual features that could be interpreted as a veiled criticism to the very ideology it aims to divulge. The crime film genre, from its constitutive proposals and its supposed ideological rigidity in a political framework such as Peronism, may grant some areas of ambiguity.
Venezuela: el empeoramiento de la situación macroeconómica y sus consecuencias
Authors: Domonkos Endre
Published: April 2019

En los últimos años Venezuela ha sido el país de América Latina y del mundo, donde la situación económica ha empeorado mucho. En 2015 y 2016 la economía del país ha sido caracterizada por la altísima tasa de inflación, el gran aumento del precio de los alimentos básicos, y una enorme contracción de la actividad económica. En mi ensayo quiero prestar atención a las causas que contribuyeron al deterioro de la economía venezolana, pero no voy a ocuparme a la evaluación de la situación crítica en la política del país.
Extracorporeal LDL-Cholesterol Elimination in the Treatment of Severe Familial Hypercholesterolemia
Authors: Bláha Milan
Published: April 2019

The extracorporeal elimination of LDL-cholesterol could be performed using the classic non-selective centrifuge or membrane plasmapheresis. The modern methods are more selective and effective. The atherogenic particules are removed from plasma by active colon or capsula. The methods include: cascade filtration, imunoadsorbtion, heparin-induced precipitation of LDL, thermofiltration, dextran-induced precipitation of LDL and direct adsorption of lipids (DALI). The regular LDL-apheresis is the life-saving technique in the treatment of homozygous familial hypercholesterolaemia. It is used in heterozygous familial hypercholesterolaemia when the patients do not respond to diet and drugs therapy, too. The regular LDL-apheresis treatment may be followed by the decreased frequency of angina pain episodes, the reduction of ECG changes during the bicycle ergometry and significant disappearance of tendinous xantomas. Some prospective randomised studies has shown even in this group of patients, resistant to conventional treatment, a significant regression of atherosclerotic changes.
Image schemas in visual semiotics: Looking for an origin of plastic language
Authors: Polidoro Piero
Published: April 2019

The aim of this article is to present a hypothesis explaining the origin of plastic meaning. In visual semiotics, plastic meaning is that produced by visual configurations per se, i.e. independently from what they represent. This meaning can be assimilated to the kind of effects studied by (Arnheim, R. 1954/1974. Art and visual perception: A psychology of the creative eye, 2nd edn. Berkeley, Los Angeles, and London: University of California Press). In his book The Body In the Mind, (Johnson, M. 1987. The body in the mind. Chicago: The University of Chicago Press) is the first to propose that image schemas and their metaphorical projections could be used to explain some of these visual effects. Nevertheless, I think that his approach presents some shortcomings. Above all, Johnson’s examples always concern cases in which visual stimuli match an image schema, while Arnheim’s observations are mostly about effects of tension and dynamism generated by a conflict with our expectations. I will propose that, to complete Johnson’s proposal, we need an inferential theory of aesthetic experience, derived from Meyer’s and Eco’s works. This theory would explain how expectations and their verifications can produce different kinds of tension and arousal, the basic mechanisms of plastic meaning.
Double Poisson-Tweedie Regression Models
Authors: Petterle Ricardo R. , Bonat Wagner H. , Kokonendji Célestin C. , Seganfredo Juliane C. , Moraes Atamai , da Silva Monica G.
Published: April 2019

In this paper, we further extend the recently proposed Poisson-Tweedie regression models to include a linear predictor for the dispersion as well as for the expectation of the count response variable. The family of the considered models is specified using only second-moments assumptions, where the variance of the count response has the formμ+ϕμp$\mu + \phi \mu^p$, whereµis the expectation,ϕandpare the dispersion and power parameters, respectively. Parameter estimations are carried out using an estimating function approach obtained by combining the quasi-score and Pearson estimating functions. The performance of the fitting algorithm is investigated through simulation studies. The results showed that our estimating function approach provides consistent estimators for both mean and dispersion parameters. The class of models is motivated by a data set concerning CD4 counting in HIV-positive pregnant women assisted in a public hospital in Curitiba, Paraná, Brazil. Specifically, we investigate the effects of a set of covariates in both expectation and dispersion structures. Our results showed that women living out of the capital Curitiba, with viral load equal or larger than 1000 copies and with previous diagnostic of HIV infection, present lower levels of CD4 cell count. Furthermore, we detected that the time to initiate the antiretroviral therapy decreases the data dispersion. The data set andRcode are available as supplementary materials.
Derivation method of numerous dynamics in the Special Theory of Relativity
Authors: Szostek Roman
Published: April 2019

The article presents innovative method of deriving dynamics in the Special Theory of Relativity. This method enables to derive infinitely many dynamics in relativistic mechanics. The authors have shown five examples of these derivations. In this way,It is presented that the dynamics known today as the dynamics of Special Theory of Relativity is only one of infinitely of theoretically possible.
Spiritualität und Professionalität am Beispiel der christlichen Sozialen Arbeit
Authors: Mahler Roland
Published: April 2019

Soziale Arbeit als Handlungswissenschaft hat sich den einschlägigen wissenschaftstheoretischen Anforderungen bzw. den Kriterien spezifischer Theoriemodelle zu stellen. Die vorliegende Arbeit versucht zu zeigen, wie ein Konzept der Sozialen Arbeit, welches auf der christlichen Spiritualität gründet, letztere als integrierter Bestandteil einer einschlägigen Theorie verstehen kann. Der Aufsatz bezieht sich dabei auf das christliche Grundmotiv der neo-calvinistischen Philosophie (Herman Dooyeweerd) und versucht, unter dem Stichwort der Proximalität ein Konzept der professionellen sozialen Verantwortlichkeit im Blick auf das Gleichnis vom Barmherzigen Samariter zu entwickeln.
Achtsamkeit, Weisheit und Mitgefühl
Authors: Pfeifer-Schaupp Ulrich
Published: April 2019

Der Beitrag skizziert eine buddhistische Perspektive Sozialer Arbeit. Am Anfang steht die Frage, was das erkenntnisleitende Interesse dieses Versuchs ist. Dann mache ich deutlich, auf welche Form des Buddhismus ich mich beziehe: Es geht dabei nicht um Buddhismus als Religion, sondern um angewandten Buddhismus, wie ihn z. B. Thich Nhat Hhanh vertritt bzw. um „engagierten Buddhismus“. Im Zentrum des Beitrags steht dann die Frage, welchen Erkenntnisgewinn diese neue Perspektive verspricht. Abschließend wird erörtert, wo die Anschlussfähigkeit an moderne sozialarbeitswissenschaftliche Diskurse liegt.
“Disjoint and Out of Frame”:Hamletand the Problem of Synchrony
Authors: Schlegel Johannes
Published: April 2019

Hamletstages problems of immanent synchrony that can be described as both motor and product of specific temporalities. By contemplating different timelines and even problematising the notion of linear time itself, Shakespeare’s tragedy illustrates that de/synchronisation relies on cultural techniques, which, in the context of the play, consist of the basic operations of calculating, representing, and commanding. At the same time, however, synchronisation proves to be inevitably recursive as it always already necessitates further operations. As this reading ofHamletshows, the relevance of cultural techniques becomes apparent when it is understood as a heterogeneous arrangement in which technical-practical, aesthetic, symbolic, and political concepts interact.
Cultural Techniques and the Politics of Detail: Tom McCarthy’sRemainderand/as Media Theory
Authors: Glaubitz Nicola
Published: April 2019

Tom McCarthy’s novels are informed by media theory, and this essay reads his novelRemaindernot onlywiththeory in order to highlight parallels to reflections on cultural techniques and sociotechnical networks but also tries to assess its relevanceastheory. My essay will, first of all, introduce the media theoretical framework of cultural techniques and show how cultural techniques are described inRemainder.The parallel agendas of the novel and cultural techniques research, I argue, converge in a shared interest in materiality, practices, and the seemingly banal details of everyday life but put them into different perspectives. I will then readRemainderas a contribution to the theoretical debate on cultural techniques and suggest that the novel draws our attention to a politics of detail in theories of practices, the everyday, and cultural techniques.