bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic Therapy for Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: ASCO Clinical Practice Guideline Update
Authors: Giordano Sharon H. , Temin Sarah , Chandarlapaty Sarat , Crews Jennie R. , Esteva Francisco J. , Kirshner Jeffrey J. , Krop Ian E. , Levinson Jennifer , Lin Nancy U. , Modi Shanu , Patt Debra A. , Perlmutter Jane , Ramakrishna Naren , Winer Eric P. , Davidson Nancy E.
Published: June 2018

Purpose

To update evidence-based guideline recommendations for practicing oncologists and others on systemic therapy for patients with human epidermal growth factor receptor 2 (HER2)–positive advanced breast cancer to 2018.

Methods

An Expert Panel conducted a targeted systematic literature review (for both systemic treatment and CNS metastases) and identified 622 articles. Outcomes of interest included overall survival, progression-free survival, and adverse events.

Results

Of the 622 publications identified and reviewed, no additional evidence was identified that would warrant a change to the 2014 recommendations.

Recommendations

HER2-targeted therapy is recommended for patients with HER2-positive advanced breast cancer, except for those with clinical congestive heart failure or significantly compromised left ventricular ejection fraction, who should be evaluated on a case-by-case basis. Trastuzumab, pertuzumab, and taxane for first-line treatment and trastuzumab emtansine for second-line treatment are recommended. In the third-line setting, clinicians should offer other HER2-targeted therapy combinations or trastuzumab emtansine (if not previously administered) and may offer pertuzumab if the patient has not previously received it. Optimal duration of chemotherapy is at least 4 to 6 months or until maximum response, depending on toxicity and in the absence of progression. HER2-targeted therapy can continue until time of progression or unacceptable toxicities. For patients with HER2-positive and estrogen receptor–positive/progesterone receptor–positive breast cancer, clinicians may recommend either standard first-line therapy or, for selected patients, endocrine therapy plus HER2-targeted therapy or endocrine therapy alone. Additional information is available at www.asco.org/breast-cancer-guidelines .
Recommendations on Disease Management for Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases: ASCO Clinical Practice Guideline Update
Authors: Ramakrishna Naren , Temin Sarah , Chandarlapaty Sarat , Crews Jennie R. , Davidson Nancy E. , Esteva Francisco J. , Giordano Sharon H. , Kirshner Jeffrey J. , Krop Ian E. , Levinson Jennifer , Modi Shanu , Patt Debra A. , Perlmutter Jane , Winer Eric P. , Lin Nancy U.
Published: June 2018

Purpose

To update the formal expert consensus-based guideline recommendations for practicing oncologists and others on the management of brain metastases for patients with human epidermal growth factor receptor 2–positive advanced breast cancer to 2018.

Methods

An Expert Panel conducted a targeted systematic literature review (for both systemic treatment and CNS metastases) and identified 622 articles. Outcomes of interest included overall survival, progression-free survival, and adverse events. In 2014, the American Society of Clinical Oncology (ASCO) convened a panel of medical oncology, radiation oncology, guideline implementation, and advocacy experts, and conducted a systematic review of the literature. When that failed to yield sufficiently strong quality evidence, the Expert Panel undertook a formal expert consensus–based process to produce these recommendations. ASCO used a modified Delphi process. The panel members drafted recommendations, and a group of other experts joined them for two rounds of formal ratings of the recommendations.

Results

Of the 622 publications identified and reviewed, no additional evidence was identified that would warrant a change to the 2014 recommendations.

Recommendations

Patients with brain metastases should receive appropriate local therapy and systemic therapy, if indicated. Local therapies include surgery, whole-brain radiotherapy, and stereotactic radiosurgery. Treatments depend on factors such as patient prognosis, presence of symptoms, resectability, number and size of metastases, prior therapy, and whether metastases are diffuse. Other options include systemic therapy, best supportive care, enrollment in a clinical trial, and/or palliative care. Clinicians should not perform routine magnetic resonance imaging to screen for brain metastases, but rather should have a low threshold for magnetic resonance imaging of the brain because of the high incidence of brain metastases among patients with HER2-positive advanced breast cancer. Additional information is available at www.asco.org/breast-cancer-guidelines .
Vocal tract modelling in fallow deer: are male groans nasalized?
Authors: Reby D. , Wyman M. T. , Frey R. , Charlton B. D. , Dalmont J. P. , Gilbert J.
Published: June 2018

Males of several species of deer have a descended and mobile larynx, resulting in an unusually long vocal tract, which can be further extended by lowering the larynx during call production. Formant frequencies are lowered as the vocal tract is extended, as predicted when approximating the vocal tract as a uniform quarter wavelength resonator. However, formant frequencies in polygynous deer follow uneven distribution patterns, indicating that the vocal tract configuration may in fact be rather complex. We CT-scanned the head and neck region of two adult male fallow deer specimens with artificially extended vocal tracts and measured the cross-sectional areas of the supra-laryngeal vocal tract along the oral and nasal tracts. The CT data was then used to predict the resonances produced by three possible configurations, including the oral vocal tract only, the nasal vocal tract only, or combining both. We found that the area functions from the combined oral and nasal vocal tracts produced resonances more closely matching the formant pattern and scaling observed in fallow deer groans than those predicted by the area functions of the oral vocal tract only or of the nasal vocal tract only. This indicates that the nasal and oral vocal tracts are both simultaneously involved in the production of a nonhuman mammal vocalisation, and suggests that the potential for nasalization in putative oral loud-calls should be carefully considered.
Waddle and shuffle: Gait alterations associated with domestication in turkeys
Authors: Stover Kristin K. , Brainerd Elizabeth L. , Roberts Thomas J.
Published: June 2018

Domestication has altered turkey morphology by artificially selecting for increased muscle mass and breast meat. Artificial selection has resulted in birds that weigh up to three times more than their wild counterparts, with relatively little change in the length of their bones and limbs. Considering these structural changes, it seems probable that domestic turkey locomotor kinematics and kinetics would also be altered. To examine the locomotor dynamics of wild and domestic turkeys we had both strains walk down a runway with a force plate at the center to measure their ground reaction forces and gait parameters. The location of their center of mass was also quantified using a force plate and bi-planar x-ray and found to be further anterior in the domestic strain. The domestic turkeys locomoted across a lower range of speeds (0.25-1.64 ms−1) than the wild turkeys (0.26-3.26 ms−1) and increased their stride frequency at a higher rate. They also displayed large lateral oscillations, i.e. waddling, during walking that translated into relatively high medio-lateral ground reaction forces and lateral kinetic energy (3.5 times higher than wild turkeys). Results indicate that domestic turkey locomotion is not simply a slowed down version of wild turkey locomotion. The changes in gait observed are similar to the shuffling gait present in some human populations, such as Parkinson's patients, which serves to increase stability. The domestic turkey's increased body mass and more anterior center of mass position may require these kinematic and kinetic gait differences.
Limits to sustained energy intake XXVIII: Beneficial effects of high dietary fat on lactation performance in mice
Authors: Kagya-Agyemang J. K. , Vaanholt L. M. , Hambly C. , Król E. , Mitchell S. E. , Speakman J. R.
Published: June 2018

Maximal animal performance may be limited by the ability of animals to dissipate heat; the heat dissipation limitation (HDL) theory. Since diets vary in the incidental heat produced during digestion (specific dynamic action, SDA), the HDL theory predicts lactating female mice consuming diets with lower SDA should have increased reproductive performance. Dietary fat has a lower SDA than dietary carbohydrate. Female mice were fed low (LF), medium (MF) or high fat (HF) diets (10%, 45% and 60% energy from fat respectively) from days 4-18 of lactation. HF and MF-fed mice weaned significantly heavier litters than LF mice. This was because they not only consumed more energy (metabolisable energy intake, Emei; HF:306.5±25.0, MF:340.5±13.5 kJ d−1) at peak lactation, but also delivered more milk energy to their pups (milk energy output, Emilk: 203.2±49.9, 229.3±42.2 kJ d−1 respectively) than the LF-fed mice (Emei =266.7±4.5, Emilk =164.60±30.59 kJ d−1). This effect was greater than predicted from the SDA of the different diets combined with a mathematical model based on the HDL theory. Fatty acid profiles of the diets, milk and pups, showed significant correlations between the profiles. Besides reduced SDA, HF and MF-fed mice were probably able to directly transfer absorbed dietary fat into milk, reducing the heat production of lactogenesis, and enabling them to perform better than expected from the HDL model. In summary, HF and MF diets had beneficial effects on reproductive performance compared to the LF diet because they enabled mice to generate milk more efficiently with less incidental heat production.
An in vivo test of the biologically relevant roles of carotenoids as antioxidants in animals
Authors: Weaver Ryan J. , Wang Philip , Hill Geoffrey E. , Cobine Paul A.
Published: June 2018

Carotenoids are well known for their contribution to the vibrant coloration of many animals and have been hypothesized to be important antioxidants. Surprisingly few examples of carotenoids acting as biologically relevant antioxidants in vivo exist, in part because experimental designs often employ dosing animals with carotenoids at levels that are rarely observed in nature. Here we use an approach that reduces carotenoid content from wild-type levels to test for the effect of carotenoids as protectants against an oxidative challenge. We used the marine copepod, Tigriopus californicus reared on a carotenoid-free or a carotenoid-restored diet of nutritional yeast and then exposed them to a prooxidant. We found that carotenoid-deficient copepods not only accumulated more damage, but also were more likely to die during an oxidative challenge than carotenoid-restored copepods. We suggest that carotenoid reduction, and not supplementation, better tests the proposed roles of carotenoids in other physiological functions in animals.
T-2 mycotoxin induced apoptosis in broiler’s liver tissue
Authors: Hussar Piret , Järveots Tõnu , Pendovski Lazo , Blagoevska Katerina , Ristoski Trpe , Popovska-Percinic Florina
Published: June 2018

Apoptosis is a process of programmed cell death that occurs in multicellular organisms. As T-2 toxin is known to induce apoptosis in mammalian cells, the aim of the present experiment was to study the toxic effect of T-2 on chicken liver tissue using apoptosis-related antibodies p21 and p53 which are involved in the p53/p21-mediated apoptotic signalling pathway.

The experiment was conducted on fourteen 40-day-old broilers (Gallus gallus domesticus) who were divided into control and T-2 toxin groups. For the T-2 toxin group, T-2 toxin (Sigma, Germany) was dissolved in water and given per os for three consecutive days. The material of the liver was taken 24 hours after the last application. The specimens were fixed with 10% formalin and embedded into paraffin; slices 5 μm in thickness were cut followed by immunohistochemical staining with polyclonal primary antibodies p21 and p53 (Abcam, UK) according to the manufacturer’s guidelines (IHC kit, Abcam, UK).

Strong expression of p21 and p53 found in hepatocytes, endotheliocytes and around blood vessels together with large tissue destructions in T-2 toxin group birds’ liver indicates apoptosis and histopathological changes in liver tissue during T-2 mycotoxicosis.
THE INSTITUTE OF THE MARRIAGE CONTRACT IN RUSSIA
Authors: Гдалевич Ирина , Gdalevich Irina , Бородкина Светлана , Borodkina Svetlana
Published: June 2018

This article discusses the concept of the marriage contract, its legal purpose. A number of aspects related to the nature of the marriage contract, which is understood as a kind of civil contracts to establish or change the legal regime of property. In addition, the article analyzes positive and negative aspects of the registration of the marriage contract, the conditions of concluding and terminating
Adjustments to the Tax Code of the Russian Federation: in the Interests of the Breakthrough Development of the Economy
Authors: Смирнов Е. , Smirnov E.
Published: June 2018

Adjustments made in the Tax Code of the Russian Federation by Federal Law No. 335-FZ of November 27, 2017 are aimed at further improving the country’s tax system in line with the state’s eff orts to the breakthrough development of the economy in the short term and create an optimal balance of interests of economic relations participants.
Audit of Ecological Payments
Authors: Золотарева Г. , Zolotareva G. , Денисенко Галина , Denisenko Galina
Published: June 2018

Results of the conducted research are presented in article in the fi eld of control of ecological activity and prevention of possible penalties by means of audit of ecological payments. Emergence of audit of ecological payments as independent direction allows the auditor to concentrate on fi nancial check of payments tax and non-tax character (ecological payments). In the off ered work categories of payments which should be carried to ecological payments are described, expediency of division of functions of audit of ecological payments and ecological audit is proved, the order of carrying out audit of ecological payments as main instrument of fi nancial control of ecological aspects of the economic subject in the fi eld of environmental protection is presented.
Acute appendicitis
Authors: Пугаев Андрей , Pugaev Andrey , Ачкасов Евгений , Achkasov Evgeniy
Published: June 2018

Acute appendicitis is a disease with which the surgeon faces in providing emergency surgical care both in the most famous clinic and in the hospital far from a large city. Before acute appendicitis are equal and novice doctors, and gray-haired professors and academics.
The use of modern technologies, of course, had a positive impact on the results of surgical treatment of patients with acute appendicitis. However, the problem of acute appendicitis is far from being solved.
This book reflects the experience of the authors of diagnosis and treatment of patients with acute appendicitis for 40 years, which allowed to formulate General provisions of diagnostic and treatment tactics and postoperative management of patients.
We hope that the book will be useful to a wide range of doctors and, of course, surgeons, especially those who are starting their professional activities.
The first edition of the book in 2011 aroused a positive response and great interest among surgeons, and the published edition of the book, which seemed at first quite sufficient, was quickly exhausted. Repeated appeals to the authors to purchase this monograph were the reason for the need to prepare the second edition of the book that you hold in your hands.
APRENDER NO FACEBOOK: ALGUNS SILÊNCIOS E RUÍDOS PARA INSTIGAR O ENSINO E A DOCÊNCIA ONLINE
Authors: Da Silva Bruno Vieira Alves , Bairral Marcelo Almeida
Published: June 2018

Cada vez mais as tecnologias da informação e comunicação (TIC) tornam mais rápida e dinâmica a comunicação, a interação e o compartilhamento de conteúdo entre as pessoas. Essa investigação busca refletir sobre contribuições do Facebook como espaço de aprendizagem em uma disciplina do Mestrado em Educação do PPGEduc/UFRRJ. A disciplina transcorreu em sua maior parte no Facebook e os participantes tiveram oportunidade de explorar as ferramentas disponibilizadas no grupo e de refletir coletivamente a partir de diferentes propostas de discussão. Os dados foram gerados a partir das interações no próprio grupo. O software Nodelx foi utilizado para analisar a não linearidade e a hipertextualidade presentes no processo interativo nesta rede. A análise elucida ruídos e silêncios observados na dinâmica interativa neste grupo. Ruídos foram caracterizados a partir das interações relacionadas às discussões que aconteciam no grupo. Como silêncios são denominados os rastros silenciosos dos membros ao utilizar a rede, mesmo sem interagir nela.
SOU FRANCO, MARIELLE FRANCO
Authors: Carmo Alessandro Xavier do
Published: June 2018

O objetivo deste poema é analisar de forma sintética e alegórica a trajetória da mulher Marielle Franco.O mesmo vislumbra apontar possíveis dilemas e dores originados de atos discriminatórios e vislumbra se apropriar dos signos de crônicas policiais para trazer à baila a morte dos jovens da favela da maré e o assassinato de nossa atuante parlamentar.Tal alegoria visa especular sobre um possível incômodo gerado por nossa sempre PRESENTE vereadora, pois a mesma era contundente em apontar  os excessos cometidos pelo  Estado legalmente constitúido e a atuação do poder paralelo.
RESEARCH ROUNDUP
Authors: Costello John
Published: June 2018

John Costello provides a synopsis and brief review of a selection of recently published research articles of interest to neuroscience nurses, highlighting the key points to keep you up to date. A full reference is provided for those who wish to read the research in more detail.
Preparing to take an active role as citizens
Authors: Davis John
Published: June 2018

Use this guide to the basics of Britain's political system to fire children's interest in government, how it operates and how it impacts their lives and local communities.
High-Sensitivity Cardiac Troponin-Based Strategies for the Assessment of Chest Pain Patients—A Review of Validation and Clinical Implementation Studies
Authors: Eggers Kai M , Jernberg Tomas , Ljung Lina , Lindahl Bertil
Published: June 2018

BACKGROUND

The introduction of high-sensitivity cardiac troponin (hs-cTn) assays has improved the early assessment of chest pain patients. A number of hs-cTn-based algorithms and accelerated diagnostic protocols (ADPs) have been developed and tested subsequently. In this review, we summarize the data on the performance and clinical utility of these strategies.

CONTENT

We reviewed studies investigating the diagnostic and prognostic performance of hs-cTn algorithms [level of detection (LoD) strategy, 0/1-h, 0/2-h, and 0/3-h algorithms) and of hs-cTn-based ADPs, together with the implications of these strategies when implemented as clinical routine. The LoD strategy, when combined with a nonischemic electrocardiogram, is best suited for safe rule-out of myocardial infarction and the identification of patients eligible for early discharge from the emergency department. The 0/1-h algorithms appear to identify most patients as being eligible for rule-out. The hs-cTn-based ADPs mainly focus on prognostic assessment, which is in contrast with the hs-cTn algorithms. They identify smaller proportions of rule-out patients, but there is increasing evidence from prospective studies on their successful clinical implementation. Such information is currently lacking for hs-cTn algorithms.

CONCLUSIONS

There is a trade-off between safety and efficacy for different hs-cTn-based strategies. This trade-off should be considered for the intended strategy, along with its user-friendliness and evidence from clinical implementation studies. However, several gaps in knowledge remain. At present, we suggest the use of an ADP in conjunction with serial hs-cTn results to optimize the early assessment of chest pain patients.
The EuBIVAS: Within- and Between-Subject Biological Variation Data for Electrolytes, Lipids, Urea, Uric Acid, Total Protein, Total Bilirubin, Direct Bilirubin, and Glucose
Authors: Aarsand Aasne K , Díaz-Garzón Jorge , Fernandez-Calle Pilar , Guerra Elena , Locatelli Massimo , Bartlett William A , Sandberg Sverre , Røraas Thomas , Ceriotti Ferruccio , Sølvik Una Ørvim , Sverresdotter Sylte Marit , Coşkun Abdurrahman , Serteser Mustafa , Unsal Ibrahim , Tosato Francesca , Plebani Mario , Jonker Niels , Barla Gerhard , Carobene Anna
Published: June 2018

BACKGROUND

The European Federation of Clinical Chemistry and Laboratory Medicine European Biological Variation Study (EuBIVAS) has been established to deliver rigorously determined data describing biological variation (BV) of clinically important measurands. Here, EuBIVAS-based BV estimates of serum electrolytes, lipids, urea, uric acid, total protein, total bilirubin, direct bilirubin, and glucose, as well as their associated analytical performance specifications (APSs), are presented.

METHOD

Samples were drawn from 91 healthy individuals (38 male, 53 female; age range, 21–69 years) for 10 consecutive weeks at 6 European laboratories. Samples were stored at −80 °C before duplicate analysis of all samples on an ADVIA 2400 (Siemens Healthineers). Outlier and homogeneity analyses were performed, followed by CV-ANOVA on trend-corrected data, when relevant, to determine BV estimates with CIs.

RESULTS

The within-subject BV (CVI) estimates of all measurands, except for urea and LDL cholesterol, were lower than estimates available in an online BV database, with differences being most pronounced for HDL cholesterol, glucose, and direct bilirubin. Significant differences in CVI for men and women/women <50 years of age were evident for uric acid, triglycerides, and urea. The CVA obtained for sodium and magnesium exceeded the EuBIVAS-based APS for imprecision.

CONCLUSIONS

The EuBIVAS, which is fully compliant with the recently published Biological Variation Data Critical Appraisal Checklist, has produced well-characterized, high-quality BV estimates utilizing a stringent experimental protocol. These new reference data deliver revised and more exacting APS and reference change values for commonly used clinically important measurands, thus having direct relevance to diagnostics manufacturers, service providers, clinical users, and ultimately patients.
Early numerical cognition and mathematical processes
Authors: Pantsar Markus
Published: June 2018

In this paper I study the development of arithmetical cognition with the focus on metaphorical thinking. In an approach developing on Lakoff and Núñez (2000), I propose one particular conceptual metaphor, the Process → Object Metaphor (POM), as a key element in understanding the development of mathematical thinking.
Manipulative imagination: how to move things around in mathematics
Authors: Giardino Valeria
Published: June 2018

In the first part of the paper, previous work about embodied mathematics and the practice of topology will be presented. According to the proposed view, in order to become experts, topologists have to learn how to use manipulative imagination: representations are cognitive tools whose functioning depends from pre-existing cognitive abilities and from specific training. In the second part of the paper, the notion of imagination as “make-believe” is discussed to give an account of cognitive tools in mathematics as props; to better specify the claim, the notion of “affordance” is explored in its possible extension from concrete objects to representations.
Qualidade físico-química e microbiológica da água em reservatórios subterrâneos na cidade de Vitória da Conquista-BA para fins de potabilidade
Authors: Dourado Aline Aguiar , Ferraz Lorena Lima , Silva Adeid Rodrigues Santos , Rocha Felizardo Adenilson
Published: June 2018

O presente estudo teve como objetivo avaliar e apresentar os resultados do monitoramento da qualidade físico-química e microbiológica da água subterrânea da cidade de Vitória da Conquista, localizada no sudoeste da Bahia, verificando sua conformidade com a legislação. Foram escolhidos seis poços tubulares distribuídos na área urbana da cidade e que atendem residências, condomínios e instituições federais de ensino. O estudo analisou os parâmetros temperatura, pH, potencial de oxirredução (ORP), turbidez, cor, sólidos totais dissolvidos (STD), oxigênio dissolvido (OD), demanda bioquímica de oxigênio (DBO), salinidade, coliformes totais e coliformes termotolerantes ao longo de sete meses de monitoramento mensal ininterrupto. Foi observado que os parâmetros pH, cor, turbidez, DBO e oxigênio dissolvido encontram-se fora da faixa permitida na maioria dos poços analisados. Um dos poços apresentou contaminação por coliformes totais e termotolerantes, se mostrando imprópria para consumo humano. Conclui-se que os poços estudados carecem de tratamento convencional ou simplificado para atingir os níveis de potabilidade aceitáveis. O monitoramento das variáveis físico-químicas e microbiológicas ajudou a melhorar o banco de dados sobre a qualidade das águas subterrâneas da cidade.
Detection of a novel, primate-specific ‘kill switch’ tumor suppression mechanism that may fundamentally control cancer risk in humans: an unexpected twist in the basic biology of TP53
Authors: Nyce Jonathan W
Published: June 2018

The activation of TP53 is well known to exert tumor suppressive effects. We have detected aprimate-specificadrenal androgen-mediated tumor suppression system in which circulating DHEAS is converted to DHEA specifically in cells in which TP53 has beeninactivated. DHEA is anuncompetitiveinhibitor of glucose-6-phosphate dehydrogenase (G6PD), an enzyme indispensable for maintaining reactive oxygen species within limits survivable by the cell. Uncompetitive inhibition is otherwise unknown in natural systems because it becomesirreversiblein the presence of high concentrations of substrate and inhibitor. In addition to primate-specific circulating DHEAS, a unique, primate-specific sequence motif that disables an activating regulatory site in the glucose-6-phosphatase (G6PC) promoter was also required to enable function of this previously unrecognized tumor suppression system. In human somatic cells, loss of TP53 thus triggers activation of DHEAS transport proteins and steroid sulfatase, which converts circulating DHEAS into intracellular DHEA, and hexokinase which increases glucose-6-phosphate substrate concentration. The triggering of these enzymes in the TP53-affected cell combines with the primate-specific G6PC promoter sequence motif that enables G6P substrate accumulation, driving uncompetitive inhibition of G6PD to irreversibility and ROS-mediated cell death. By this catastrophic ‘kill switch’ mechanism, TP53 mutations are effectively prevented from initiating tumorigenesis in the somatic cells of humans, the primate with the highest peak levels of circulating DHEAS. TP53 mutations in human tumors therefore represent fossils of kill switch failure resulting from an age-related decline in circulating DHEAS, a potentially reversible artifact of hominid evolution.
Ovarian and extra-ovarian mediators in the development of polycystic ovary syndrome
Authors: Puttabyatappa Muraly , Padmanabhan Vasantha
Published: June 2018

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder affecting women of reproductive age. The origin of PCOS is still not clear and appears to be a function of gene × environment interactions. This review addresses the current knowledge of the genetic and developmental contributions to the etiology of PCOS, the ovarian and extra-ovarian mediators of PCOS and the gaps and key challenges that need to be addressed in the diagnosis, treatment and prevention of PCOS.
The proneural bHLH genes Mash1, Math3 and NeuroD are required for pituitary development
Authors: Ando Mitsushige , Goto Masanori , Hojo Masato , Kita Aya , Kitagawa Masashi , Ohtsuka Toshiyuki , Kageyama Ryoichiro , Miyamoto Susumu
Published: June 2018

Multiple signaling molecules and transcription factors are required for pituitary development. Activator-type bHLH genesMash1,Math,NeuroD (Neurod)and Neurogenin(Neurog)are well known as key molecules in neural development. Although analyses of targeted mouse mutants have demonstrated involvement of these bHLH genes in pituitary development, studies with single-mutant mice could not elucidate their exact functions, because they cooperatively function and compensate each other. The aim of this study was to elucidate the roles ofMash1,Math3andNeuroDin pituitary development.Mash1;Math3;NeuroDtriple-mutant mice were analyzed by immunohistochemistry and quantitative real-time RT-PCR. Misexpression studies with retroviruses in pituisphere cultures were also performed. The triple-mutant adenohypophysis was morphologically normal, though the lumen of the neurohypophysis remained unclosed. However, in triple-mutant pituitaries, somatotropes, gonadotropes and corticotropes were severely decreased, whereas lactotropes were increased. Misexpression ofMash1alone with retrovirus could not induce generation of hormonal cells, thoughMash1was involved in differentiation of pituitary progenitor cells. These data suggest thatMash1,Math3andNeuroDcooperatively control the timing of pituitary progenitor cell differentiation and that they are also required for subtype specification of pituitary hormonal cells.Mash1is necessary for corticotroph and gonadotroph differentiation, and compensated byMath3andNeuroD.Math3is necessary for somatotroph differentiation, and compensated byMash1andNeuroD.Neurog2may compensateMash1,Math3andNeuroDduring pituitary development. Furthermore,Mash1,Math3andNeuroDare required for neurohypophysis development. Thus,Mash1,Math3andNeuroDare required for pituitary development, and compensate each other.
Sodium butyrate supplementation ameliorates diabetic inflammation in db/db mice
Authors: Xu You-Hua , Gao Chen-Lin , Guo Heng-Li , Zhang Wen-Qian , Huang Wei , Tang Shan-Shan , Gan Wen-Jun , Xu Yong , Zhou Hua , Zhu Quan
Published: June 2018

Endotoxemia has been recognized to be closely accompanied with type 2 diabetes mellitus (T2DM) and is responsible for many diabetic complications. Recent study suggests the potential role of butyrate, a short-chain fatty acid (SCFA) from microbiota metabolite, on T2DM. Gut-leak is a key event in diabetic-endotoxemia. To investigate if butyrate could ameliorate diabetic-endotoxemia, both in vivo and in vitro experiments were carried out in the present study. The effect of butyrate supplementation on blood HbA1c and inflammatory cytokines were determined in db/db mice; gut barrier integrity and expression of tight junction proteins were investigated both in vivo and in vitro. Oral butyrate administration significantly decreased blood HbA1c, inflammatory cytokines and LPS in db/db mice; inflammatory cell infiltration was reduced, and gut integrity and intercellular adhesion molecules were increased as detected by HE staining, immunohistochemistry and Western blot. By gut microbiota assay, ratio of Firmicutes:Bacteroidetes for gut microbiota was reduced by butyrate. In Caco-2 cells, butyrate significantly promoted cell proliferation, decreased inflammatory cytokines’ secretion, enhanced cell anti-oxidative stress ability and preserved the epithelial monocellular integrity, which was damaged by LPS. The present findings demonstrated that butyrate supplementation could ameliorate diabetic-endotoxemia in db/db mice via restoring composition of gut microbiota and preserving gut epithelial barrier integrity.
Programming of the reproductive axis by hormonal and genetic manipulation in mice
Authors: Rulli Susana B , Cambiasso María Julia , Ratner Laura D
Published: June 2018

In mammals, the reproductive function is controlled by the hypothalamic-pituitary-gonadal axis. During development, mechanisms mediated by gonadal steroids exert an imprinting at the hypothalamic-pituitary level, by establishing sexual differences in the circuits that control male and female reproduction. In rodents, the testicular production of androgens increases drastically during the fetal/neonatal stage. This process is essential for the masculinization of the reproductive tract, genitals and brain. The conversion of androgens to estrogens in the brain is crucial for the male sexual differentiation and behavior. Conversely, feminization of the brain occurs in the absence of high levels of gonadal steroids during the perinatal period in females. Potential genetic contribution to the differentiation of brain cells through direct effects of genes located on sex chromosomes is also relevant. In this review, we will focus on the phenotypic alterations that occur on the hypothalamic-pituitary-gonadal axis of transgenic mice with persistently elevated expression of the human chorionic gonadotropin hormone (hCG). Excess of endogenously synthesized gonadal steroids due to a constant hCG stimulation is able to disrupt the developmental programming of the hypothalamic-pituitary axis in both transgenic males and females. Locally produced estrogens by the hypothalamic aromatase might play a key role in the phenotype of these mice. The “four core genotypes” mouse model demonstrated a potential influence of sex chromosome genes in brain masculinization before critical periods of sex differentiation. Thus, hormonal and genetic factors interact to regulate the local production of the neurosteroids necessary for the programming of the male and female reproductive function.
The Prenatal Visit
Authors: Yogman Michael , Lavin Arthur , Cohen George ,   COMMITTEE ON PSYCHOSOCIAL ASPECTS OF CHILD AND FAMILY HEALTH, Lemmon Keith M. , Mattson Gerri , Rafferty Jason Richard , Wissow Lawrence Sagin
Published: June 2018

A pediatric prenatal visit during the third trimester is recommended for all expectant families as an important first step in establishing a child’s medical home, as recommended by Bright Futures: Guidelines for Health Supervision of Infants, Children, and Adolescents, Fourth Edition. As advocates for children and their families, pediatricians can support and guide expectant parents in the prenatal period. Prenatal visits allow general pediatricians to establish a supportive and trusting relationship with both parents, gather basic information from expectant parents, offer information and advice regarding the infant, and may identify psychosocial risks early and high-risk conditions that may require special care. There are several possible formats for this first visit. The one used depends on the experience and preference of the parents, the style of the pediatrician’s practice, and pragmatic issues of payment.
Phytochemical and Antibacterial Activities of Combined Leaves and Flower Extracts of English Camphor Basil (Ocimum canum) on Some Selected Bacteria Associated with Skin Infections
Authors: G.M Gberikon, , A. D Dabo, , E.B Agbo,
Published: June 2018

Phytochemical and antibacterial activities of combined leaves and flower extracts of English camphor basil (Ocimum canum) on some selected bacteria associated with skin infections was investigated. Plant samples were collected at Mista Ali, Bassa LGA of Plateau State. Phytochemical analysis was carried out in the Biochemistry Laboratory of National Veterinary Research Institute Vom (NVRI), located in Jos South LGA. The test organisms, S. aureus, S. pyogenes, P. aeruginosa, S. marcescens, E. faecalis were obtained from the microbial banks of bacteriology and dermatophilosis sections of NVRI, Vom and were standardized with a Nephelometer.  Quantitatively, the leaves and flower ethanolic extracts were tested individually and in combination against bacteria associated with skin infections both extracts showed the presence of steroids, cardiac glycosides and flavonoids while tannins were detected in the leaves extract only. There was significant (p<0.05) variation in the quantity of inherent phytochemical components of the extracts. Cardiac glycoside had the highest concentrations (0.64±0.02 and 0.54±0.02) in the leaves and flower extracts respectively. Leaves extract showed activity against test bacteria except E. faecalis. Strains of S. pyogenes and S. aureus were only susceptible to flower extract. The MBC ranged from 50-100mg/ml for the sensitive bacterial isolates. Fractional Inhibitory Concentration Index (FICI) from the combined extracts varied from 1.89 to 3.97 on the test bacteria that showed lack of interaction (FICI<4). Thus, combination of leaves and flower of O. canum may not exhibit any advantage. However, the plant contain bioactive constituents of pharmacological significance and should be explore for more potentials.
Gambling disorder and obsessive–compulsive personality disorder: A frequent but understudied comorbidity
Authors: Medeiros Gustavo C. , Grant Jon E.
Published: June 2018

Background and aims

Epidemiological data have suggested that the prevalence of co-occurring personality disorders is particularly high in people with gambling disorder (GD). Among the personality disorders, obsessive–compulsive personality disorder (OCPD) appears to be the most common problem. The objective of this study was to investigate the clinical presentation of GD with and without co-occurring OCPD.

Methods

We studied 25 subjects with current GD and lifetime diagnosis of OCPD. They were matched for age and gender with 25 individuals with current GD but no lifetime diagnosis of any personality disorder.

Results

Subjects with GD and OCPD demonstrated (a) lower severity of gambling symptoms, (b) slower progression from recreational gambling to full-blown GD, (c) preferred individual forms of betting, (d) identified more triggers to gambling (specially the availability of money and stress); and (e) reported less negative impact on relational problems due to GD.

Conclusions

Our research provides further insight on GD co-occurring with OCPD, such as increasing social support and improvement of coping skills, especially to deal with financial difficulties and stress. Our findings may lead to more customized and effective therapeutic approaches to this frequent comorbidity.
Az anyák és az újszülöttek megmentője, akire mindig büszkék leszünk: Semmelweis Ignác (1818–1865). Aki legyőzte a kórt, de nem győzte meg a kort, az orvostudományok és a sebészet doktora, szülészmester, a Pesti Királyi Magyar Tudományegyetemen az elméleti és gyakorlati szülészet nyilvános, rendes tanára
Authors: Rosivall László
Published: June 2018

Abstract:

Semmelweis finally achieved results from his persistent research work. Those being the scientific analysis of clinical statistical data and his animal experiments, which recognized the dreadful disease of puerperal fever and its prevention. “He not only discovered the real cause of puerperal fever but he also created antiseptic prophylaxis, which he introduced in obstetrics and laid the foundations of modern surgery (asepsis). The theory and practice of asepsis stemmed from the discovery of the etiology of puerperal fever and therefore originating from the genius idea of Semmelweis. The discoveries of bacteriology by Lister, Pasteur and Koch only provided a scientific proof of the intuitive statements of Semmelweis.” Semmelweis was a pioneer of clinical etiological research whose findings were aggressively disapproved by his colleagues due to earlier medical misunderstandings. Semmelweis is given due respect by posterity as a remuneration, to all the bitterness that he had suffered throughout his life. Semmelweis is considered the savior of mothers and infants. The Hungarian nation is very proud of him as he is one of our models whose oeuvre is acknowledged not only in Hungary but throughout the world. The message of his short, tragic yet effective life is eternal. The figure of Ignác Semmelweis is depicted as a statue and is placed in Chicago among the statues of the most innovative doctors and health care professionals of the world. The statue of Semmelweis is next to the statues of Louis Pasteur and Wilhelm Conrad Röntgen. “Semmelweis reflex” is a new expression which appeared and spread in English speaking countries. The word does not relate to a medical phenomenon but describes a social phenomenon when experts or the whole society automatically rejects discoveries and new recognitions without examination or justification. This phenomenon frequently occurs, even in our times. Orv Hetil. 2018; 159(26): 1041–1054.
Grátis não é o suficiente: estudo da adoção individual da telefonia pela internet
Authors: Cappellozza Alexandre , Sanchez Otávio Próspero
Published: June 2018

Estudos têm demonstrado a existência de diversos fatores de influência da adoção de Tecnologias da Informação. Para a operacionalização de uma análise de adoção de tecnologia que englobe múltiplas interações de influências, optou-se pela contextualização do estudo com foco na telefonia pela Internet, pois quando comparada com outras tecnologias de comunicação, a gratuidade de ligações é um dos principais benefícios, aliada a outros recursos. A pesquisa fundamenta-se em uma abordagem quantitativa, onde os dados foram obtidos com a participação de 313 usuários de telefonia pela Internet. Realizou-se análise de equações estruturais para confirmar relações entre os fatores. Os resultados indicam que o hábito influencia mais o uso gratuito desta tecnologia do que a percepção dos benefícios do uso em si, apesar da ausência de custos das ligações ser um dos principais incentivos à adoção da tecnologia. Evidencia-se que a rede de contatos do usuário é o principal responsável pela formação do hábito de uso das tecnologias de comunicação. A disponibilidade também se mostrou um fator à formação do hábito. Sob o ponto de vista dos interessados em promover o uso de tecnologias inovadoras de comunicação, este estudo contribui na exposição de fatores que promove a adoção destes sistemas.
Medalha de ouro! Estudo sobre motivação no trabalho voluntário eventual nos Jogos Olímpicos no Rio de Janeiro
Authors: Pereira Helio Araújo , Cavalcante Carlos Eduardo
Published: June 2018

Este artigo tem por objetivo identificar os fatores motivacionais dos voluntários eventuais envolvidos com eventos esportivos no Brasil. A parte empírica do artigo tem como lócus os jogos olímpicos realizados no Rio de Janeiro no ano de 2016. Os dados empíricos foram coletados a partir do modelo teórico de Bang e Chelladurai (2009), que começaram o desenvolvimento dessa base teórica nos jogos olímpicos, em Atenas, em 2004. Foi utilizado o método quantitativo de pesquisa, envolvendo a aplicação de 400 questionários junto aos voluntários envolvidos nos jogos olímpicos do Rio de Janeiro. A pesquisa evidenciou, na seguinte ordem, que os maiores fatores motivacionais voltados ao esporte no Brasil estão relacionados às variáveis: expressão de valores, amor ao esporte e contatos interpessoais. Observou-se ainda, que a variável motivacional, extrínseco, foimenos relevante para os voluntários.
Modelo de Avaliação de Satisfação dos Agricultores Familiares em Relação ao Programa de Aquisição de Alimentos do Governo Federal
Authors: Teotonio do Nascimento Daniel , Johann Jerry Adriani , Basso Dirceu
Published: June 2018

As receitas arrecadadas pelo Estado são quase sempre insuficientes para atender todas as demandas da cidadania, portanto, é primordial uma aplicação eficiente dos recursos estatais nas políticas públicas implementadas. Quando se avaliam as políticas públicas toda a sociedade é beneficiada com os resultados, pois em base aos diagnósticos, algumas ações podem ser melhoradas e outras redirecionadas. Este artigo teve como propósito desenvolver um Modelo de Avaliação de Satisfação (MAS) dos agricultores familiares em relação ao Programa de Aquisição de Alimentos (PAA), modalidade Compra com Doação Simultânea (CDS). O MAS possui duas finalidades: a) detectar o grau de satisfação dos agricultores familiares em relação à política pública PAA; e b) avaliar o grau de satisfação dos agricultores familiares em relação à gestão das cooperativas ou associações. Em base à literatura e legislações correlatas ao tema, alcançou-se um modelo inovador e abrangente, com grande potencial de aplicabilidade. O modelo pretende contribuir para uma maior efetividade na coleta padronizada de percepções sobre o PAA, posto que o MAS poderá ser aplicado em qualquer região do Brasil, possibilitando ajustes operacionais e socioeconômicos pelos órgãos públicos e cooperativas, melhorando dessa forma a eficiência da política pública e dos processos organizacionais das cooperativas.
The integration of a new simulation center within a Competency-Based Curriculum: an opportunity for holistic undergraduate medical education curriculum redesign
Authors: Weis Joshua J , Wagner James , Farr Deborah E , Ginsburg Charles , Guttman Oren , Krumwiede Kim Hoggatt , Kho Kimberly A , Martinez Joseph , Reed Gary , Rege Robert V , Sulistio Melanie S , Scott Daniel J
Published: June 2018

This article was migrated. The article was not marked as recommended. Problem: Medical education is shifting to competency based training focusing on 13 Core EPA's for Entering Residency. In response, UME leaders are reforming curricula to focus on Competency Based Education (CBE), and many institutions are choosing to incorporate Simulation Based Educations (SBE) into these efforts. Guidance for institutions planning comprehensive reform and simulation integration is limited. The purpose of this paper is to describe the experience at one medical school attempting to align a new UME curriculum and a new simulation center using CBE principles.Approach: As part of a UME curriculum redesign, the University of Texas Southwestern took two major actions. First, they secured funding to build a campus wide simulation center to host large-scale, high-quality simulation activities. Second, they formed a simulation planning committee to coordinate existing simulation activities and develop new activities to integrate into the new curriculum. This committee chose to use EPAs as an organizing framework.Outcome: The simulation planning committee carefully identified 25 simulation activities that would effectively target core EPAs, while also complementing existing UME courses. The committee identified a director and co-director for each activity and established standard elements that would be common to all simulation activities. Learners' progress through each activity is tracked and verified in a comprehensive portfolio.Next Steps: Throughout the academic year, data will be collected for each simulation activity according to uniform metrics. These data will be used to inform the committee's decisions to continue, modify, or discontinue certain activities for future cohorts of students.
Primary health care attributes assessment: children and adolescents living with HIV
Authors: Antunes Bibiana Sales , Padoin Stela Maris de Mello , Paula Cristiane Cardoso de
Published: June 2018

Abstract Objectives: To evaluate the attributes derived from Primary Health Care (PHC) focusing on children and adolescents living with HIV, in the experience of health professionals, comparing traditional units (BHU) and Family Health Strategy (FHS). Method: Cross-sectional research in which 524 professionals from 25 cities of Rio Grande do Sul, Brazil were interviewed. The Primary Care Assessment Tool Brazil was used from March through August 2014. Results: The PHC score attributed to FHS (7.8) was higher than that attributed to BHU (6.8). The higher scores contributed to the home visit, the professional qualification and the employment bond, the latter acting independently of the others. Conclusion: The satisfactory evaluation of the derived attributes approves the interaction with users and community and the potential of PHC to attend these children and adolescents, and the home visit qualifies the practice.