bluuebunny/crossref_metadata_2025 huggingface dataset:
Cold water immersion attenuates anabolic signaling and skeletal muscle fiber hypertrophy, but not strength gain, following whole-body resistance training
Authors: Fyfe Jackson J. , Broatch James R. , Trewin Adam J. , Hanson Erik D. , Argus Christos K. , Garnham Andrew P. , Halson Shona L. , Polman Remco C. , Bishop David J. , Petersen Aaron C.
Published: September 2019

We determined the effects of cold water immersion (CWI) on long-term adaptations and post-exercise molecular responses in skeletal muscle before and after resistance training. Sixteen men (22.9 ± 4.6 y; 85.1 ± 17.9 kg; mean ± SD) performed resistance training (3 day/wk) for 7 wk, with each session followed by either CWI [15 min at 10°C, CWI (COLD) group, n = 8] or passive recovery (15 min at 23°C, control group, n = 8). Exercise performance [one-repetition maximum (1-RM) leg press and bench press, countermovement jump, squat jump, and ballistic push-up], body composition (dual X-ray absorptiometry), and post-exercise (i.e., +1 and +48 h) molecular responses were assessed before and after training. Improvements in 1-RM leg press were similar between groups [130 ± 69 kg, pooled effect size (ES): 1.53 ± 90% confidence interval (CI) 0.49], whereas increases in type II muscle fiber cross-sectional area were attenuated with CWI (−1,959 ± 1,675 µM2 ; ES: −1.37 ± 0.99). Post-exercise mechanistic target of rapamycin complex 1 signaling (rps6 phosphorylation) was blunted for COLD at post-training (POST) +1 h (−0.4-fold, ES: −0.69 ± 0.86) and POST +48 h (−0.2-fold, ES: −1.33 ± 0.82), whereas basal protein degradation markers (FOX-O1 protein content) were increased (1.3-fold, ES: 2.17 ± 2.22). Training-induced increases in heat shock protein (HSP) 27 protein content were attenuated for COLD (−0.8-fold, ES: −0.94 ± 0.82), which also reduced total HSP72 protein content (−0.7-fold, ES: −0.79 ± 0.57). CWI blunted resistance training-induced muscle fiber hypertrophy, but not maximal strength, potentially via reduced skeletal muscle protein anabolism and increased catabolism. Post-exercise CWI should therefore be avoided if muscle hypertrophy is desired.

NEW & NOTEWORTHY This study adds to existing evidence that post-exercise cold water immersion attenuates muscle fiber growth with resistance training, which is potentially mediated by attenuated post-exercise increases in markers of skeletal muscle anabolism coupled with increased catabolism and suggests that blunted muscle fiber growth with cold water immersion does not necessarily translate to impaired strength development.
An Analytical Solution to the Electromagnetic Performance of an Ultra-High-Speed PM Motor
Authors: Cheng Wenjie , Deng Zhikai , Xiao Ling , Zhong Bin , Sun Yanhua
Published: September 2019

Bipolar rotors with cylindrical permanent magnets (PMs), which are magnetized in parallel, are generally used in ultra-high-speed permanent magnet synchronous motors (PMSMs). Aiming for this type of PMSM, two methods, namely, the Poynting theorem and the Maxwell stress tensor, were used to deduce the analytic expression of the electromagnetic driving torque. A locked-rotor simulation by the finite element (FE) method verifies the analytical solution. In addition, the cogging torque, back-electromotive force (emf), armature reaction inductance, etc., were calculated, compared, and discussed. The no-load back-emf was checked by a 60,000 rpm free coast experiment. The proposed analytical solution is very convenient to guide the design of the ultra-high-speed PMSM and check its performance.
Human Hepatocytes and Differentiated Adult-Derived Human Liver Stem/Progenitor Cells DisplayIn VitroImmunosuppressive Properties Mediated, at Least in Part, through the Nonclassical HLA Class I Molecule HLA-G
Authors: Lombard Catherine A. , Sana Gwenaëlle , LeMaoult Joël , Najar Mehdi , Ravau Joachim , André Floriane , Bouhtit Fatima , Daouya Marina , Loustau Maria , Najimi Mustapha , Lagneaux Laurence , Carosella Edgardo D. , Sokal Etienne M.
Published: September 2019

One of the main challenges in liver cell therapy (LCT) is the induction of a tolerogenic microenvironment to promote graft acceptance in the recipient. Little is known about the immunomodulatory potential of the hepatic cells used in liver cell therapy. In this work, we wanted to evaluate the immunosuppressive properties of human hepatocytes and adult-derived human liver stem/progenitor cells (ADHLSCs), as well as the potential involvement of the immunomodulatory molecule HLA-G. We demonstrated that both cell types were capable of inhibiting the proliferative response of PBMCs to an allogenic stimulus and that the immune inhibitory potential of ADHLSCs, although lower than that of hepatocytes, increased after hepatogenic differentiation. We demonstrated that liver cells express HLA-G and that the immune inhibition pattern was clearly associated to its expression. Interestingly, HLA-G expression increased after the third step of differentiation, wherein oncostatin M (OSM) was added. A 48 hr treatment with OSM was sufficient to induce HLA-G expression in ADHLSCs and result in immune inhibition. Surprisingly, blocking HLA-G partially reversed the immune inhibition mediated by hepatocytes and differentiated ADHLSCs, but not that of undifferentiated ADHLSCs, suggesting that additional immune inhibitory mechanisms may be used by these cells. In conclusion, we demonstrated that both hepatocytes and ADHLSCs present immunomodulatory properties mediated, at least in part, through HLA-G, which can be upregulated following hepatogenic differentiation or liver cell pretreatment with OSM. These observations open up new perspectives for the induction of tolerance following LCT and for potential therapeutic applications of these liver cells.
Multiobjective Optimization Design for Structural Parameters of TBM Disc Cutter Rings Based on FAHP and SAMPGA
Authors: Lin Laikuang , Xia Yimin , Wu Dun
Published: September 2019

As a key component of tunnel boring machines (TBMs), the disc cutter ring and its structural parameters are closely related to the TBM tunneling quality. Literature review shows that investigations on optimization design methods for cutter ring structure are seriously insufficient. Therefore, in this paper, a multiobjective optimization design model of structural parameters for disc cutter rings is developed based on the complex geological conditions and the corresponding cutter ring structure design requirements. The rock breaking capability, energy consumption, load‐bearing capability, wear life, and wear uniformity of disc cutter are selected as the objectives, and the geometric structure of cutter rings, ultimate load‐bearing capability, and cutterhead drive performance are determined as constraints. According to the characteristics of this model, a self‐adaptive multipopulation genetic algorithm (SAMPGA) is utilized to solve the optimization problem, and the Fuzzy analytical hierarchy process (FAHP) is employed to calculate weight coefficients for multiple objectives. Finally, the applicability of the proposed method is demonstrated through a case study in a TBM project. The results indicated that the rock breaking performance and service life of the disc cutter are improved after optimization by using the proposed method. The utilization of SAMPGA effectively solves the premature local convergence problems during optimization. The geological adaptability should be considered in the cutter ring structure design, which can be realized by using the proposed method based on the suitable weight coefficients.
Role of Plasma Calreticulin in the Prediction of Severity in Septic Patients
Authors: Xu Zhiheng , Yang Yuanyuan , Zhou Jianmeng , Huang Yongbo , Wang Ya , Zhang Yu , Lan Yuan , Liang Jie , Liu Xiaoqing , Zhong Nanshan , Li Yimin , Mao Pu
Published: September 2019

Background. Calreticulin has been identified to play a critical role in innate and adaptive immune responses. However, little is known about the role of calreticulin in sepsis with a characteristic of immune disorder. This study was aimed at investigating whether plasma calreticulin level increases in sepsis and its association with sepsis severity. Methods. This retrospective analysis evaluated sepsis patients who were admitted to the intensive care unit (ICU). Healthy subjects were also included as controls. Plasma samples were collected from the patients within 48 h after ICU admission as well as the healthy subjects. Plasma calreticulin levels were measured via the enzyme-linked immunosorbent assay. Results. In total, 127 sepsis patients and 40 healthy controls were included. Calreticulin was significantly increased in sepsis patients than in healthy controls. Furthermore, the level of plasma calreticulin was significantly higher in nonsurvivors than in survivors. Patients with calreticulin levels>343.5 pg/ml showed lower cumulative survival than those with levels<343.5 pg/ml. Conclusion. Calreticulin level was positively correlated with the severity of sepsis. High calreticulin level indicated poor prognosis of sepsis patients.
Immunogenic Evaluation of Ribosomal P-Protein Antigen P0, P1, and P2 and Pentameric Protein Complex P0-(P1-P2)2ofPlasmodium falciparumin a Mouse Model
Authors: Szuster-Ciesielska Agnieszka , Wawiórka Leszek , Krokowski Dawid , Grankowski Nikodem , Jarosz Łukasz , Lisiecka Urszula , Tchórzewski Marek
Published: September 2019

Malaria remains one the most infectious and destructive protozoan diseases worldwide.Plasmodium falciparum, a protozoan parasite with a complex life cycle and high genetic variability responsible for the difficulties in vaccine development, is implicated in most malaria-related deaths. In the course of study, we prepared a set of antigens based on P-proteins fromP. falciparumand determined their immunogenicity in anin vivoassay on a mouse model. The pentameric complex P0-(P1-P2)2was prepared along with individual P1, P2, and P0 antigens. We determined the level of cellular- and humoral-type immunological response followed by development of specific immunological memory. We have shown that the number of Tc cells increased significantly after the first immunization with P2 and after the second immunization with P1 and P0-(P1-P2)2, which highly correlated with the number of Th1 cells. P0 appeared as a poor inducer of cellular response. After the third boost with P1, P2, or P0-(P1-P2)2, the initially high cellular response dropped to the control level accompanied by elevation of the number of activated Treg cells and a high level of suppressive TGF-β. Subsequently, the humoral response against the examined antigens was activated. Although the titers of specific IgG were increasing during the course of immunization for all antigens used, P2 and P0-(P1-P2)2were found to be significantly stronger than P1 and P0. A positive correlation between the Th2 cell abundance and the level of IL-10 was observed exclusively after immunization with P0-(P1-P2)2. Anin vitroexposure of spleen lymphocytes from the immunized mice especially to the P1, P2, and P0-(P1-P2)2protein caused 2-3-fold higher cell proliferation than that in the case of lymphocytes from the nonimmunized animals, suggesting development of immune memory. Our results demonstrate for the first time that the native-like P-protein pentameric complex represents much stronger immune potential than individual P-antigens.
Arterial Stiffness and Indices of Left Ventricular Diastolic Dysfunction in Patients with Embolic Stroke of Undetermined Etiology
Authors: Gąsiorek Paulina , Sakowicz Agata , Banach Maciej , von Haehling Stephan , Bielecka-Dabrowa Agata
Published: September 2019

Purpose. The study is aimed at identifying echocardiographic and circulating biomarkers as well as hemodynamic indices of embolic stroke of undetermined etiology (ESUS) in patients aged <65. Methods. We prospectively investigated 520 patients with confirmed ischemic stroke and selected those 65 patients who were diagnosed with ESUS (age 54 (47-58) years, 42% male). An additional 36 without stroke but with a similar risk profile were included as a control group (age 53 (47-58) years, 61% male). All patients underwent echocardiography, noninvasive assessment of hemodynamic parameters using a SphygmoCor tonometer (AtCor Med., Australia), and measurements of selected biomarkers. Results. ESUS patients and controls were well matched for baseline characteristics including blood pressure and left ventricular ejection fraction (LVEF). Compared to controls, patients with ESUS had lower mean early diastolic (E′) and systolic (S′) mitral annular velocities and a higher ratio of the peak velocity of early diastolic transmitral flow to the peak velocity of early diastolic mitral annular motion (all p<0.01). The peak velocity flow in the late diastole (A wave) value and LV mass indexed to the body surface area (LVMI) (g/m2) were higher in the ESUS group than in the control group (both p<0.01). The isovolumetric relaxation time (IVRT) was longer and the mean left atrial volume index (LAVI) was higher in ESUS patients compared to the control group. Parameters of arterial stiffness such as augmentation pressure, augmentation index, and augmentation index adjusted to a heart rate of 75 bpm (AIx75) were higher in ESUS patients compared to controls (p<0.05). Patients in the ESUS group had higher levels of asymmetric dimethylarginine, interleukin 6, and N-terminal probrain natriuretic peptide (NT-proBNP, all p<0.05) than those in the control group. In multivariate analysis, the following factors were significantly associated with the presence of ESUS: AIx75 (odds ratio (OR) 1.095, 95% confidence interval (CI) 1.004-1.194; p=0.04), IVRT (OR 1.045, 95% CI: 1.009-1.082; p=0.014), LAVI (OR 1.3, 95% CI: 1.099-1.537; p=0.002), and NT-proBNP (OR 1.003, 95% CI: 1.001-1.005; p=0.005). Conclusions. Increased arterial stiffness and indices of diastolic dysfunction as well as a higher NT-proBNP level are significantly associated with ESUS. These parameters require further scrutiny over time to understand their impact on the development of symptomatic heart failure. The ClinicalTrials.gov identifier is NCT03377465.
Improving Response to FLT3 Inhibitors–BCL2 the Rescue?
Authors: Perl Alexander E.
Published: September 2019

As single agents, FLT3 inhibitors are active in FLT3-mutated acute myeloid leukemia (AML) therapy but not curative. The BCL2 inhibitor, venetoclax, enhances responses to low intensity AML chemotherapy but its activity is limited by MCL1 upregulation. FLT3 inhibitors downregulate MCL1 and synergize with venetoclax in preclinical AML models.

See related article by Ma et al., p. 6815
Mirc11Disrupts Inflammatory but Not Cytotoxic Responses of NK Cells
Authors: Nanbakhsh Arash , Srinivasamani Anupallavi , Holzhauer Sandra , Riese Matthew J. , Zheng Yongwei , Wang Demin , Burns Robert , Reimer Michael H. , Rao Sridhar , Lemke Angela , Tsaih Shirng-Wern , Flister Michael J. , Lao Shunhua , Dahl Richard , Thakar Monica S. , Malarkannan Subramaniam
Published: September 2019

Natural killer (NK) cells generate proinflammatory cytokines that are required to contain infections and tumor growth. However, the posttranscriptional mechanisms that regulate NK cell functions are not fully understood. Here, we define the role of the microRNA cluster known as Mirc11 (which includes miRNA-23a, miRNA-24a, and miRNA-27a) in NK cell–mediated proinflammatory responses. Absence of Mirc11 did not alter the development or the antitumor cytotoxicity of NK cells. However, loss of Mirc11 reduced generation of proinflammatory factors in vitro and interferon-γ–dependent clearance of Listeria monocytogenes or B16F10 melanoma in vivo by NK cells. These functional changes resulted from Mirc11 silencing ubiquitin modifiers A20, Cbl-b, and Itch, allowing TRAF6-dependent activation of NF-κB and AP-1. Lack of Mirc11 caused increased translation of A20, Cbl-b, and Itch proteins, resulting in deubiquitylation of scaffolding K63 and addition of degradative K48 moieties on TRAF6. Collectively, our results describe a function of Mirc11 that regulates generation of proinflammatory cytokines from effector lymphocytes.
Prognostic Implications of Influenza Virus Infection in a Cardiac Intensive Care Unit: Potential Impact of a Screening Program
Authors: Muñoz Patricia , Vicent Lourdes , Bouza Emilio , Sousa-Casasnovas Iago , López-Roa Paula , Juárez Miriam , Eworo Alia , Devesa Carolina , Bruña Vanesa , Catalán Pilar , Fernández-Avilés Francisco , Martínez-Sellés Manuel
Published: September 2019

Objectives: Our goal was to determine the presentation and prognosis of influenza in an intensive cardiac care unit and to analyze the impact of an active surveillance program in the diagnosis. Methods: We performed a prospective registry during the flu season in a coronary unit. In the first phase, no systematic screening was performed. Systematic influenza A and B detection was performed in a second phase for all patients admitted. Results: From 227 patients, we identified 17 (7.5%) with influenza. Influenza patients were more likely to have a non-ischemic cause of admission (14 patients [82.4%] vs. 48 patients [40.3%], p = 0.002), fever (8 patients [47.1%] vs. 3 patients [2.6%], p < 0.001), and respiratory failure (7 patients [41.2%] vs. 8 patients [7%], p = 0.001). Influenza infection was an independent predictor of mortality (odds ratio 12.0, 95% confidence interval 1.9–13.6, p < 0.001). The incidence of influenza was 6.6% (6 patients) when no active screening was performed and 7.9% (11 patients) when systematic detection was performed (p = 0.005). The time to diagnosis was shorter in the systematic screening phase (0.92 ± 1.6 vs. 5.2 ± 3.8 days, p = 0.01). Conclusions: Influenza affects approximately 8% of patients admitted to an intensive cardiac care unit during the flu season, with a high mortality rate. An active surveillance program improves early detection.
“Homomorphic” Tumor Metastases as an Endodiagnostic Clue: A Case Series of Renal-Cell Carcinoma Metastatic to the Stomach
Authors: Weissman Simcha , Mehta Tej I. , Zhornitskiy Alex , Tondon Rashmi , Tabibian James H.
Published: September 2019

Distinguishing between a primary malignancy and a metastasis can be challenging in some cases. Herein, we describe 2 cases of gastric lesions that were endoscopically sampled and ultimately found to be metastatic from a renal-cell carcinoma. In both cases, the gastric metastases were endoscopically homomorphic to the primary organ (the kidney); i.e., grossly resembling and thus providing an endoscopic clue as to the primary tumor source. We report on the evaluation of obscure metastatic gastric involvement of malignancy and present the concept of homomorphism as a potential diagnostic clue in determining the source of unknown and often unsuspected primary malignancy.
Antihypertensive and Renoprotective Effects of Dietary Flaxseed and its Mechanism of Action in Deoxycorticosterone Acetate-Salt Hypertensive Rats
Authors: Watanabe Yusuke , Ohata Kaori , Fukanoki Ayaka , Fujimoto Naoto , Matsumoto Maruri , Nessa Naseratun , Toba Hiroe , Kobara Miyuki , Nakata Tetsuo
Published: September 2019

Background/Aims: Flaxseed contains alpha-linolenic acid (ALA), lignans, and dietary fiber, and its intake lowers blood pressure in hypertensive patients. Here, we examined the effects of flaxseed powder, which includes all flaxseed components, flaxseed oil, composed mainly of ALA, flaxseed lignan, and flaxseed fiber, on hypertension and renal damage induced by deoxycorticosterone acetate (DOCA)-salt. Then, we investigated the mechanisms of action associated with the effects of flaxseed. Methods: Flaxseed powder, oil, lignan, or fiber was administered to DOCA-salt rats. Systolic blood pressure (SBP), urinary protein excretion, renal angiotensin converting enzyme (ACE) activity, sympathetic nerve activity, and gene expression of inflammatory mediators in the kidney and hypothalamus were measured. Results: Flaxseed powder and oil reduced the increases in SBP and urinary protein excretion induced by DOCA-salt treatment, whereas lignan and fiber had no effects. Flaxseed oil suppressed the increase in renal ACE activity, sympathetic nerve activity, and gene expression of renal and hypothalamic inflammatory mediators. Conclusion: Flaxseed has antihypertensive and renoprotective effects in DOCA-salt rats. These effects are likely principally exerted by ALA. Furthermore, the suppression of renal ACE activity, sympathetic nerve activity, and inflammation is partly involved in the effects of flaxseed.
Chemoradiotherapy with Concurrent Regional Arterial Chemotherapy for Locally Bulky Unresectable Rectal Cancer: A Case Series
Authors: Huang Wenpeng , Wu Jiaming , Liu Gui , Lv Yongchang , Huang Jinqiu , Li Wanlang
Published: September 2019

Introduction: We evaluated the feasibility and efficacy of chemoradiotherapy with concurrent regional arterial chemotherapy (CRT/RAC) for locally bulky unresectable rectal cancer (LBURC). Case Presentation: We retrospectively reviewed 9 patients with LBURC who received CRT/RAC between January 2012 and December 2018. The regimen consisted of chemoradiotherapy and 3 cycles of regional arterial chemotherapy. Surgery was performed 6 weeks after completion of radiotherapy. The median longest tumor diameter was 10 cm (range 8.2–13.6). Grade 3 toxicity and postoperative complications occurred in 3 and 4 patients, respectively. All patients showed partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST). One patient refused the operation after completion of the scheduled regimen but then had a bowel obstruction and had to undergo urgent surgery. Of the 8 patients who underwent scheduled surgery, all had R0 resection without multivisceral resection; 3 achieved pathological complete response and 5 exhibited good tumor regression. The median follow-up period was 35 months (range 9–63). Recurrences occurred in 3 of 9 patients (pelvic relapses in 2 and lung in 1). Conclusion: CRT/RAC appeared to be beneficial to LBURC, as it achieves remarkable rates of R0 resection, good tumor regression, and pathologic complete response. These preliminary results have to be confirmed in larger cohorts of patients.
Construção do pensamento e das práticas científicas
Authors: Monteiro Canale Ricardo Angelo
Published: September 2019

Este artigo tem por pretensão analisar a construção e o processo do pensamento e do conhecimento científico e suas práticas na era industrial e pós-industrial. Além disso, o artigo demonstra a relação entre os diferentes grupos científicos e suas práticas (e.g. teórica, experimental ou instrumental) para: i) a troca de objetos de conhecimento e divulgação científica; ii) a formação crítica dos sujeitos; iii) o desenvolvimento de Estado; e iv) a dominação social.

 

Palavras-chave: Ciência. Pensamento científico. Difusão e divulgação do conhecimento científico. Zonas de troca. Estado e sociedade.
As Memórias Econômicas de Domingos Vandelli sobre o carvão combustível no fim do século XVIII
Authors: Costa Ricardo Dalla
Published: September 2019

A partir do estudo das Memórias Econômicas de Domingos Vandelli, e em especial, um estudo de caso sobre o carvão mineral para fins de combustível, apresenta-se uma vertente do final do século XVIII português, no que diz respeito às expedições no Reino à procura de um produto que pudesse reduzir as importações, e ao mesmo tempo, na análise do uso de turfa ou carvão de terra como substitutos nos momentos de grande escassez do carvão mineral daquele período. Por fim, o uso do betume como subproduto comercial.
Os Usos públicos do passado como fonte para a o estudo do desastre da talidomida na Espanha
Authors: Janz Jr Dones Claudio
Published: September 2019

A teratogenia provocada pela talidomida em bebês é considerada pela ciência como um dos grandes desastres farmacêuticos do século XX. Fabricada por uma empresa alemã, a Grünenthal, a droga foi comercializada em mais de 40 países a partir do final da década de 1950, afetando milhares de crianças. Na Espanha, a talidomida ocupa espaço na mídia até os dias atuais, sobretudo, por conta das ações da Associação de Vítimas da Talidomida na Espanha (AVITE). A AVITE, ao buscar a reparação às vítimas, atua em indiferentes instâncias. Nesse artigo analisaremos algumas das ferramentas utilizadas publicamente pela associação, buscando demonstrar como elas são acionadas na luta por justiça aos afetados.
A dimensão geográfica da técnica
Authors: Pereira Leandro Serra Silva
Published: September 2019

Este trabalho tem como objetivo exaltar a dimensão geográfica da técnica. Na introdução, será exposta uma ampla noção de como a aplicação desigual das técnicas são o fundamento da crise que o sistema-mundo capitalista vivencia em suas múltiplas escalas. Na segunda sessão, serão abordadas algumas temáticas pertinentes à filosofia da técnica, ou seja, questões referentes às subjetividades do “fazer técnico”. Por fim, defendemos que as ideologias que permeiam as técnicas e tecnologias são materializadas geograficamente pelas ações dos agentes sociais, que disputam o poder e a reprodução de suas normas e símbolos nos espaços.
Conhecimento científico
Authors: Rosetto Marcia
Published: September 2019

O papel da informação e do conhecimento para as pessoas e as organizações pode ser analisada pelo menos em duas dimensões – filosófica e tecnológica –, e faz parte das transformações sociais e desempenhando um papel central na sociedade. Para a ciência, tanto a informação como o conhecimento, devem ter suas origens documentadas sendo que o fluxo da informação científica é determinado pelos padrões adotados e na forma de sua mediação e comunicação. Na área de História da Ciência (HC)  o documento é um dos principais recursos para o desenvolvimento de pesquisas, incluindo os processos que permitem o acesso ao documento nas coleções/repositórios, assim como as classificações, terminologias e as formas de comunicação e divulgação desses conteúdos. Os estudos historiográficos na área da Ciência da Informação (CI) sobre “documento e informação” remetem aos projetos promovidos por Paul Otlet e Henry La Fontaine, que consolidaram bibliografias, repertórios e teorias e processos para a organização e acesso à massa documental, e são considerados como uma das raízes da CI. Para a área da HC,  os estudos e projetos organizados por George Sarton o identificam como um dos principais articuladores para a institucionalização da área e sendo responsável pela criação da revista Isis e a Bibliographie Analytique des Publications Relatives à l’Histoire de la Science, entre outros tipos de documentos. Durante a realização da pesquisa no âmbito do Programa de Pós-Graduandos em História da Ciência da PUC/SP, com o uso de múltiplas fontes, foram identificados fatores das possíveis inter-relações entre essas duas áreas que tem características interdisciplinares.
Editorial
Authors: Magalhães Gildo
Published: September 2019

Editorial do número
Perivascular Adipocytes in Vascular Disease
Authors: Kim Ha Won , Belin de Chantemèle Eric J. , Weintraub Neal L.
Published: September 2019

Perivascular adipocytes residing in the vascular adventitia are recognized as distinct endocrine cells capable of responding to inflammatory stimuli and communicating with the sympathetic nervous system and adjacent blood vessel cells, thereby releasing adipocytokines and other signaling mediators to maintain vascular homeostasis. Perivascular adipocytes exhibit phenotypic heterogeneity (both white and brown adipocytes) and become dysfunctional in conditions, such as diet-induced obesity, thus promoting vascular inflammation, vasoconstriction, and smooth muscle cell proliferation to potentially contribute to the development of vascular diseases, such as atherosclerosis, hypertension, and aortic aneurysms. Although accumulating data have advanced our understanding of the role of perivascular adipocytes in modulating vascular function, their impact on vascular disease, particularly in humans, remains to be fully defined. This brief review will discuss the mechanisms whereby perivascular adipocytes regulate vascular disease, with a particular emphasis on recent findings and current limitations in the field of research.
Endothelial Targets in Stroke
Authors: Andjelkovic Anuska V. , Xiang Jianming , Stamatovic Svetlana M. , Hua Ya , Xi Guohua , Wang Michael M. , Keep Richard F.
Published: September 2019

Cerebral ischemia (stroke) induces injury to the cerebral endothelium that may contribute to parenchymal injury and worsen outcome. This review focuses on current preclinical studies examining how to prevent ischemia-induced endothelial dysfunction. It particularly focuses on targets at the endothelium itself. Those include endothelial tight junctions, transcytosis, endothelial cell death, and adhesion molecule expression. It also examines how such studies are being translated to the clinic, especially as adjunct therapies for preventing intracerebral hemorrhage during reperfusion of the ischemic brain. Identification of endothelial targets may prove valuable in a search for combination therapies that would specifically protect different cell types in ischemia.
Impaired Regeneration Contributes to Poor Outcomes in Diabetic Peripheral Artery Disease
Authors: Fadini Gian Paolo , Spinetti Gaia , Santopaolo Marianna , Madeddu Paolo
Published: September 2019

Diabetes mellitus increases the risk and accelerates the course of peripheral artery disease, making patients more susceptible to ischemic events and infections and delaying tissue healing. Current understanding of pathogenic mechanisms is mainly based on the negative influence of diabetes mellitus on atherosclerotic disease and inflammation. In recent years, the novel concept that diabetes mellitus can impinge on endogenous regenerative processes has been introduced. Diabetes mellitus affects regeneration at the local level, disturbing proper angiogenesis, collateral artery formation, and muscle repair. Recent evidence indicates that an impairment in vascular mural cells, alias pericytes, may participate in diabetic peripheral vasculopathy. Moreover, the bone marrow undergoes a global remodeling, consisting of microvessels and sensory neurons rarefaction and fat accumulation, which creates a hostile microenvironment for resident stem cells. Bone marrow remodeling is also responsible for detrimental systemic effects. In particular, the aid of reparative cells from the bone marrow is compromised: these elements are released in an improper manner and become harmful vectors of inflammatory and antiangiogenic molecules and noncoding RNAs. This new understanding of impaired regeneration is inspiring new therapeutic options for the treatment of ischemic complications in people with diabetes mellitus.
ALDH2 (Aldehyde Dehydrogenase 2) Protects Against Hypoxia-Induced Pulmonary Hypertension
Authors: Zhao Yu , Wang Bailu , Zhang Jian , He Dayu , Zhang Qun , Pan Chang , Yuan Qiuhuan , Shi Yinan , Tang Haiyang , Xu Feng , Wei Shujian , Chen Yuguo
Published: September 2019

Objective:

Hypoxia-induced pulmonary hypertension (HPH) increases lipid peroxidation with generation of toxic aldehydes that are metabolized by detoxifying enzymes, including ALDH2 (aldehyde dehydrogenase 2). However, the role of lipid peroxidation and ALDH2 in HPH pathogenesis remain undefined.

Approach and Results:

To determine the role of lipid peroxidation and ALDH2 in HPH, C57BL/6 mice, ALDH2 transgenic mice, and ALDH2 knockout (ALDH2
−/−
) mice were exposed to chronic hypoxia, and recombinant tissue-specific ALDH2 overexpression adeno-associated viruses were introduced into pulmonary arteries via tail vein injection for ALDH2 overexpression. Human pulmonary artery smooth muscle cells were used to elucidate underlying mechanisms in vitro. Chronic hypoxia promoted lipid peroxidation due to the excessive production of reactive oxygen species and increased expression of lipoxygenases in lung tissues. 4-hydroxynonenal but not malondialdehyde level was increased in hypoxic lung tissues which might reflect differences in detoxifying enzymes. ALDH2 overexpression attenuated the development of HPH, whereas ALDH2 knockout aggravated it. Specific overexpression of ALDH2 using AAV1 (adeno-associated virus)-ICAM (intercellular adhesion molecule) 2p-ALDH2 and AAV2-SM22αp (smooth muscle 22 alpha)-ALDH2 viral vectors in pulmonary artery smooth muscle cells, but not endothelial cells, prevented the development of HPH. Hypoxia or 4-hydroxynonenal increased stabilization of HIF (hypoxia-inducible factor)-1α, phosphorylation of Drp1 (dynamin-related protein 1) at serine 616, mitochondrial fission, and pulmonary artery smooth muscle cells proliferation, whereas ALDH2 activation suppressed the latter 3.

Conclusions:

Increased 4-hydroxynonenal level plays a critical role in the development of HPH. ALDH2 attenuates the development of HPH by regulating mitochondrial fission and smooth muscle cell proliferation suggesting ALDH2 as a potential new therapeutic target for pulmonary hypertension.
Arterial Stiffness Modulates the Association of Resting Heart Rate With Rapid Renal Function Decline in Individuals With Type 2 Diabetes Mellitus
Authors: Liu Jian-Jun , Liu Sylvia , Gurung Resham L , Ang Keven , Ee Tang Wern , Sum Chee Fang , Tavintharan Subramaniam , Hadjadj Samy , Lim Su Chi
Published: September 2019

Objective:

Resting heart rate (RHR) has been associated with cardiovascular risk, but data on renal outcomes are still scarce. We aimed to study the association of RHR with rapid renal function decline (RRFD) and to explore whether the association of RHR with RRFD is modulated by arterial stiffness in individuals with type 2 diabetes mellitus.

Approach and Results:

One thousand one hundred forty-two Asian people with type 2 diabetes mellitus were followed for 3.9±0.9 years in a regional hospital and a primary care facility. RRFD was defined as eGFR decline of 5 mL/min per 1.73 m2 or greater per year. Arterial stiffness was assessed by carotid-femoral pulse wave velocity. One hundred sixty-eight participants (15%) were classified as having RRFD. Participants with elevated RHR were younger, had higher levels of HbA1c, albuminuria, C-reactive protein, and pulse wave velocity. Compared with the lowest quartile, participants in quartile 4 had a higher risk for RRFD after adjustment for known risk factors (adjusted odds ratio 1.91 [1.11–3.28]). RHR improved discrimination and net reclassification for prediction of RRFD above traditional risk factors. Remarkably, arterial stiffness modulated the association of RHR with RRFD (
P
for interaction =0.03). RHR was significantly associated with risk of RRFD only in those with increased arterial stiffness (pulse wave velocity above age-reference value 7.7 m/s).

Conclusions:

RHR independently predicts RRFD, and the association is modulated by arterial stiffness. An elevated heart rate may be one factor in the spectrum of cardiovascular risk factors associated with renal functional impairment, especially in those with type 2 diabetes mellitus and an increased arterial stiffness.
Dynamic Changes in the Molecular Signature of Adverse Left Ventricular Remodeling in Patients With Compensated and Decompensated Chronic Primary Mitral Regurgitation
Authors: McCutcheon Keir , Dickens Caroline , van Pelt Jos , Dix-Peek Therese , Grinter Sacha , McCutcheon Lindsay , Patel Atulkumar , Hale Martin , Tsabedze Nqoba , Vachiat Ahmed , Zachariah Don , Duarte Raquel , Janssens Stefan , Manga Pravin
Published: September 2019

Background:

There is no proven medical therapy that attenuates adverse left ventricular remodeling in patients with chronic primary mitral regurgitation (CPMR). Identification of molecular pathways important in the progression of left ventricular remodeling in patients with CPMR may lead to development of new therapeutic strategies.

Methods and Results:

We performed baseline echocardiographic, cardiac catheterization, and serum NT-pro-BNP analysis in patients with severe CPMR awaiting mitral valve surgery and stratified the study population into compensated or decompensated CPMR. We obtained left ventricular endomyocardial biopsies (n=12) for mRNA expression analysis, and compared baseline transcript levels of 109 genes important in volume-overload left ventricular remodeling with levels in normal hearts (n=5) and between patients with compensated (n=6) versus decompensated (n=6) CPMR. Patients were then randomized to treatment with and without carvedilol and followed until the time of surgery (mean follow-up 8.3 months) when repeat endomyocardial biopsies were obtained to correlate transcriptional dynamics with indices of adverse remodeling. CPMR was associated with increased
NPPA
expression levels (21.6-fold,
P
=0.004), decreased transcripts of genes important in cell survival, and enrichment of extracellular matrix genes. Decompensated CPMR was associated with downregulation of SERCA2 (0.77-fold,
P
=0.009) and mitochondrial gene expression levels and upregulation of genes related to inflammation, the extracellular matrix, and apoptosis, which were refractory to carvedilol therapy.

Conclusions:

Transition to decompensated CPMR is associated with calcium dysregulation, increased expression of inflammatory, extracellular matrix and apoptotic genes, and downregulation of genes important in bioenergetics. These changes are not attenuated by carvedilol therapy and highlight the need for development of specific combinatorial therapies, targeting myocardial inflammation and apoptosis, together with urgent surgical or percutaneous valve interventions.
Experimental Evaluation of a Novel Percutaneous Transseptal Catheter-Based Mitral Valve Replacement Technology
Authors: Vahl Torsten P. , Grogan Aaron , Cheng Yanping , Yi Genghua , von Oepen Randolf , Khalique Omar K. , Wallace Daniel T. , Modine Thomas , Granada Juan F.
Published: September 2019

Background:

Transcatheter mitral valve replacement is a novel therapeutic approach aiming to treat patients with severe mitral regurgitation. This study aimed to evaluate the biological and technical performance of a novel transseptal transcatheter mitral valve replacement system (Cephea Valve Technologies, Santa Cruz, CA) in a preclinical model.

Methods:

Biological performance and healing response were evaluated following open-heart surgical implantation procedures in 10 sheep utilizing an antegrade transatrial access. Valve performance was assessed with fluoroscopy, echocardiography, and histology at 30 (n=2), 60 (n=3), and 90 days (n=5). Feasibility of transseptal valve delivery and performance was tested acutely in 10 pigs.

Results:

In the chronic studies, all animals survived without problems until completion of the study. The hemodynamics of the study valves were excellent with low rates of paravalvular leak. There was no left ventricular outflow tract obstruction. Pathological evaluation showed excellent position and condition of the mitral implants without evidence for thrombosis, endocarditis, or excessive calcification. Subsequently, mitral valves were implanted in 10 pigs using a dedicated transseptal delivery system. The implants remained in stable position with excellent hemodynamic profile. Correct valve position and function was confirmed by echocardiography and autopsy.

Conclusions:

The transseptal delivery of the Cephea transcatheter mitral valve replacement system in an experimental model was feasible and safe. The chronic studies demonstrated a favorable healing response. Further human studies are needed to evaluate the performance of this novel valve system in patients with severe mitral regurgitation.
Body Mass Index Drives Changes in DNA Methylation
Authors: Sun Dianjianyi , Zhang Tao , Su Shaoyong , Hao Guang , Chen Tao , Li Quan-Zhen , Bazzano Lydia , He Jiang , Wang Xiaoling , Li Shengxu , Chen Wei
Published: September 2019

Rationale:

Previous EWASs (Epigenome-Wide Association Studies) suggest that obesity may be the cause, not a consequence, of changes in DNA methylation (DNAm). However, longitudinal observations are lacking.

Objective:

To identify 5′—cytosine—phosphate—guanine—3′ in DNA (CpG) sites associated with body mass index (BMI) and examine the temporal relationship between dynamic changes in DNAm and BMI in a longitudinal cohort.

Methods and Results:

Race-specific EWASs were performed in 995 whites and 490 blacks from the Bogalusa Heart Study. Suggestive CpG sites were further replicated in 252 whites and 228 blacks from the Georgia Stress and Heart Study. Cross-lagged panel analysis was used to examine the temporal relationship between DNAm and BMI in 439 whites and 201 blacks who were examined twice 6.2 years apart. In discovery and replication samples, 349 CpG sites (266 novel) in whites and 36 (21 novel) in blacks were identified to be robustly associated with BMI, with 8 (1 novel) CpG sites overlapping between the 2 races. Cross-lagged panel analyses showed significant unidirectional paths (P
FDR
<0.05) from baseline BMI to follow-up DNAm at 18 CpG sites in whites and 7 in blacks; no CpG sites showed significant paths from DNAm at baseline to BMI at follow-up. Baseline BMI was associated with a DNAm score (calculated from DNAm levels at the associated CpG sites) at follow-up (
P
<0.001 both in blacks and in whites).

Conclusions:

The findings provide strong evidence that obesity is the cause, not a consequence, of changes in DNAm over time.
Association of Aortic Aneurysms and Dissections With Subarachnoid Hemorrhage
Authors: Al‐Kawaz Mais , Kamel Hooman , Murthy Santosh B. , Merkler Alexander E.
Published: September 2019

Background

It is uncertain whether aortic diseases, such as aneurysm and dissection, are associated with intracranial aneurysm formation and aneurysmal subarachnoid hemorrhage (
SAH
).

Methods and Results

We used data on claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. Our exposure variable was hospitalization with an unruptured or ruptured aortic aneurysm or aortic dissection. The outcome was nontraumatic
SAH
. Variables were ascertained by
International Classification of Diseases, Ninth Revision, Clinical Modification
(

ICD
‐9‐
CM

), diagnosis codes. Survival statistics were used to calculate incidence rates. Cox proportional hazards analysis was used to examine the association between aortic aneurysm/dissection and
SAH
while adjusting for demographics, vascular risk factors, and Charlson comorbidities. Among 1 781 917 beneficiaries, 32 551 (1.8%) had a documented aortic aneurysm or dissection. During 4.6±2.2 years of follow‐up, 2538 patients (0.14%) developed a nontraumatic
SAH
. The incidence of
SAH
was 9 (95%
CI
, 7–11) per 10 000 patients per year in those with aortic aneurysm/dissection compared with 3 (95%
CI
, 3–3) per 10 000 patients per year in those without aortic aneurysm/dissection. After adjustment for demographics, stroke risk factors, and Charlson comorbidities, patients with aortic aneurysm/dissection faced an increased risk of
SAH
(hazard ratio, 1.4; 95%
CI
, 1.02–1.9;
P
=0.04).

Conclusions

In a nationally representative sample of Medicare beneficiaries, aortic aneurysm/dissection was associated with an increased risk of nontraumatic
SAH
.
Outcomes of Surgery for Brainstem Cavernous Malformations
Authors: Kearns Kathryn N. , Chen Ching-Jen , Tvrdik Petr , Park Min S. , Kalani M. Yashar S.
Published: September 2019

Background and Purpose—

The goal of this study was to systematically review the outcomes and complications after surgical resection of brain stem cavernous malformations (BCMs).

Methods—

A systematic literature review was performed using the PubMed database for studies published between 1986 and 2018. All studies comprising ≥2 patients with surgically resected BCMs and available follow-up data were included. Data extracted from studies included patient demographics, BCM location, and surgical outcomes.

Results—

Eighty-six studies comprising 2493 patients (adult and pediatric) were included for final analysis. Complete resection was achieved in 92.3% (fixed-effects pooled estimate [FE], 92.9% [91.7%–94.0%]; random-effects pooled estimate [RE], 89.4% [86.5%–92.0%]) of patients, and rehemorrhage of residual BCMs occurred in 58.6% (FE, 58.8% [49.7%–67.6%]; RE, 57.2% [43.5%–70.2%]). Postoperative morbidity occurred in 34.8% (FE, 30.9% [29.0%–32.8%]; RE, 31.1% [25.8%–36.6%]) of patients. Postoperative morbidities included motor deficit in 11.0% (FE, 9.9% [8.1%–11.7%]; RE, 11.1% [7.0%–16.0%]), sensory deficit in 6.7% (FE, 6.3% [4.8%–7.9%]; RE, 7.6% [4.5%–11.5%]), tracheostomy/gastrostomy in 6.0% (FE, 5.2% [4.3%–6.1%]; RE, 3.8% [2.6%–5.3%]), and other cranial nerve deficits in 29.4% (FE, 27.6% [25.3%–29.9%]; RE, 33.9% [25.7%–42.6%]) of patients. At final follow-up, 57.9% (FE, 57.6% [55.6%–59.6%]; RE, 57.2% [52.1%–62.3%]) and 25.9% (FE, 24.1% [22.4%–25.9%]; RE, 18.5% [14.6%–22.8%]) of patients had improvement and stability of preoperative symptoms, respectively. Mortality rate was 1.6% (FE, 1.9% [1.4%–2.5%]; RE, 1.8% [1.4%–2.5%]).

Conclusions—

High cure rates and low rates of postoperative morbidity can be achieved with surgery in patients with BCMs. Most patients had improved preoperative symptoms at final follow-up. To avoid rehemorrhage, complete resection should be the goal of surgery.
The Unity of LXX Genesis and Exodus
Authors: van der Louw Theo A. W.
Published: September 2019

Attempts to advocate multiple authorship for the Greek Pentateuch depend principally on statistics and are tenuous methodologically. Research methods from Translation Studies, applied to Genesis and Exodus, bring out their continuity. A sounding of the translational approach in Gen 2-3, Gen 27-28, Gen 48/50 and Exod 1-2 suggests that the Gen translator’s approach is shifting and flows seamlessly into that of the initial Exod chapters. Lexical and syntactic examples, too, illustrate that Exod continues or builds on or further develops the renderings found in the latter part of Gen. A natural explanation for this state of affairs is that the translator of Gen, whose approach had become increasingly idiomatic, completed Gen 50 and continued with Exod in the same vein. Our findings call for a verification of the multiple authorship hypothesis for the rest of the Pentateuch. They imply a less monolithic evaluation of LXX text-critical evidence.
Inter-religious Relations as a New Foundation for Comparative Religion
Authors: Reeh Niels
Published: September 2019

This article argues that the problems that comparative religion encountered in the 1980s and onward did not arise from the comparative project as such, but rather from the fact that comparative religion was founded on an analytical strategy that relied on defining religion. In order to overcome these problems and critique of Jonathan Z. Smith, Talal Asad and others, it is proposed that the comparative study of religion could be re-established on the basis of a different analytical strategy and more specifically on the basis of a relational perspective, in which the crucial point of departure is the finding that religions in many periods and cultural settings seem to constitute themselves in relation to at least one significant other religion. In periods and cultural settings, where religions relate to each other, we do in fact have a commonality between all religions, namely the inter-religious relation. This relation can ensure that we are not comparing things that have nothing in common. If the inter-religious relation is the point of departure, the comparative study of religion can be transformed in such a way that it is not overturned by the social constructionism or post-modernism of J. Z. Smith, Talal Asad and others.