bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the Variability of Therapeutic Indications of Medicinal Species in the Northeast of Brazil: Comparative Study
Authors: Ferreira Macedo Julimery Gonçalves , Menezes Irwin Rose Alencar de , Alves Ribeiro Daiany , de Oliveira Santos Maria , Gonçalves de Mâcedo Delmacia , Ferreira Macêdo Márcia Jordana , Vilar de Almeida Bianca , Souza de Oliveira Liana Geraldo , Pereira Leite Catarina , de Almeida Souza Marta Maria
Published: April 2018

Ethnopharmacological Relevance. This study aims to evaluate the versatility of these species and their agreement of use and/or the informants’ knowledge and verify the variability of the information on the indicated medicinal species in comparison to other species from northeastern Brazilian areas. Materials and Methods. Ethnobotanical information was acquired through interviews with 23 residents of the Quincuncá community, northeastern Brazil. From the obtained data, a comparative analysis of the therapeutic indications with other 40 areas in different biomes was conducted. For that, the relative importance index and informant consensus factor were calculated and compared to other indices evaluated in the literature. Results. A total of 39 medicinal species were cited and twenty‐six species showed similarities among their therapeutic indications; however, species as Geoffroea spinosa, Lantana camara, and others can be highlighted, present in community disease indications that were not verified for other areas. Myracrodruon urundeuva, Mimosa tenuiflora, Stryphnodendron rotundifolium, and Amburana cearensis had the greatest versatility. In the Quincuncá community, medicinal species were indicated for 49 diseases, which were grouped into 15 categories of body systems. Conclusion. This study shows the presented divergence in relation to their therapeutic use; in this point, these divergences reinforce the importance of pharmacological research.
RELAP5/MOD3.3 Analysis of the Loss of External Power Event with Safety Injection Actuation
Authors: Prošek Andrej , Matkovič Marko
Published: April 2018

The code assessment typically comprises basic tests cases, separate effects test, and integral effects tests. On the other hand, the thermal hydraulic system codes like RELAP5/MOD3.3 are primarily intended for simulation of transients and accidents in light water reactors. The plant measured data come mostly from startup tests and operational events. Also, for operational events the measured plant data may not be sufficient to explain all details of the event. The purpose of this study was therefore besides code assessment to demonstrate that simulations can be very beneficial for deep understanding of the plant response and further corrective measures. The abnormal event with reactor trip and safety injection signal actuation was simulated with the latest RELAP5/MOD3.3 Patch 05 best-estimate thermal hydraulic computer code. The measured and simulated data agree well considering the major plant system responses and operator actions. This suggests that the RELAP5 code simulation is good representative of the plant response and can complement not available information from plant measured data. In such a way, an event can be better understood.
Prevalence and Predictors of Silent Gastroesophageal Reflux Disease in Patients with Hypertension
Authors: Suyu He , Liu Yijun , Jianyu Xu , Luo Guiquan , Cao Lipeng , Long Xiaoqi
Published: April 2018

Background. Gastroesophageal reflux disease (GERD) without symptoms or silent GERD can be easily missed in patients with hypertension. We aimed to investigate the prevalence of GERD, specifically the prevalence of silent GERD in hypertensive patients, and to explore its possible predictors. Methods. Consecutive patients with hypertension referred to the cardiovascular clinic of Suining Central Hospital in 2016 were screened for this study. A Reflux Disease Questionnaire (RDQ) and an esophagogastroduodenoscopy (EGD) were employed for the evaluation of silent GERD. Included patients were divided into silent-GERD group and non-GERD control group. The demographic characteristics and antihypertensive agent prescriptions were collected and compared between the two groups. Results. The prevalence of silent GERD and GERD in patients with hypertension was 15.1% and 31.4%, respectively. 66 patients were included in the silent-GERD group, and 298 patients were included in the non-GERD control group. Abdominal obesity and untreated hypertension were positive predictors, while controlled hypertension was a negative predictor for silent GERD. The prescription of calcium channel blockers was not a predictor for it. Conclusions. High prevalence of GERD, specifically silent GERD, could be found in patients with hypertension. Abdominal obesity and untreated hypertension were positive predictors for silent GERD, while controlled hypertension was a negative predictor for it.
Intranasal Pharmacokinetics of Morphine ARER, a Novel Abuse-Deterrent Formulation: Results from a Randomized, Double-Blind, Four-Way Crossover Study in Nondependent, Opioid-Experienced Subjects
Authors: Webster Lynn R. , Pantaleon Carmela , Iverson Matthew , Smith Michael D. , Kinzler Eric R. , Aigner Stefan
Published: April 2018

Objective. To investigate the pharmacokinetics (PK) of Morphine ARER, an extended-release (ER), abuse-deterrent formulation of morphine sulfate after oral and intranasal administration. Methods. This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study assessed the PK of morphine and its active metabolite, M6G, from crushed intranasal Morphine ARER and intact oral Morphine ARER compared with crushed intranasal ER morphine following administration to nondependent, recreational opioid users. The correlation between morphine PK and the pharmacodynamic parameter of drug liking, a measure of abuse potential, was also evaluated. Results. Mean maximum observed plasma concentration (Cmax) for morphine was lower with crushed intranasal Morphine ARER (26.2 ng/mL) and intact oral Morphine ARER (18.6 ng/mL), compared with crushed intranasal ER morphine (49.5 ng/mL). The time to Cmax (Tmax) was the same for intact oral and crushed intranasal Morphine ARER (1.6 hours) and longer for crushed intranasal morphine ER (1.1 hours). Higher mean maximum morphine Cmax, Tmax, and abuse quotient (Cmax/Tmax) were positively correlated with maximum effect for drug liking (R2 ≥ 0.9795). Conclusion. These data suggest that Morphine ARER maintains its ER profile despite physical manipulation and intranasal administration, which may be predictive of a lower intranasal abuse potential compared with ER morphine.
MicroRNA Expression Profiling in Psoriatic Arthritis
Authors: Pelosi Andrea , Lunardi Claudio , Fiore Piera Filomena , Tinazzi Elisa , Patuzzo Giuseppe , Argentino Giuseppe , Moretta Francesca , Puccetti Antonio , Dolcino Marzia
Published: April 2018

Background. Psoriatic arthritis (PsA) is an inflammatory arthritis, characterized by bone erosions and new bone formation. MicroRNAs (miRNAs) are key regulators of the immune responses. Differential expression of miRNAs has been reported in several inflammatory autoimmune diseases; however, their role in PsA is not fully elucidated. We aimed to identify miRNA expression signatures associated with PsA and to investigate their potential implication in the disease pathogenesis. Methods. miRNA microarray was performed in blood cells of PsA patients and healthy controls. miRNA pathway analyses were performed and the global miRNA profiling was combined with transcriptome data in PsA. Deregulation of selected miRNAs was validated by real-time PCR. Results. We identified specific miRNA signatures associated with PsA patients with active disease. These miRNAs target pathways relevant in PsA, such as TNF, MAPK, and WNT signaling cascades. Network analysis revealed several miRNAs regulating highly connected genes within the PsA transcriptome. miR-126-3p was the most downregulated miRNA in active patients. Noteworthy, miR-126 overexpression induced a decreased expression of genes implicated in PsA. Conclusions. This study sheds light on some epigenetic aspects of PsA identifying specific miRNAs, which may represent promising candidates as biomarkers and/or for the design of novel therapeutic strategies in PsA.
Determinants of Low Birth Weight among Deliveries at a Referral Hospital in Northern Ethiopia
Authors: Hailu Lema Desalegn , Kebede Deresse Legesse
Published: April 2018

Background. Low birth weight is the leading cause of infant and child mortality and contributes to several poor health outcomes. Proper knowledge of risk factors of low birth weight is important for identifying those mothers at risk and thereby for planning and taking appropriate actions. This study investigates factors predicting occurrence of low birth weight among deliveries at Debreberhan Referral Hospital.Methods. Facility-based unmatched case-control study was conducted among deliveries that took place at Debreberhan Referral Hospital. Birth records and mothers’ ANC files were reviewed from April to June 2016. The study participants were selected by consecutive sampling technique. Data analysis was performed by SPSS version 20. Binary logistic regression analysis was performed to identify predictors of low birth weight.Result. A total of 147 birth records of babies with low birth weight (cases) and 294 birth records of babies with normal birth weight (controls) were reviewed. The birth weight of low birth weight babies (cases) ranged from 1000 grams to 2400 grams with median (±IQR) of 2200 grams (±300 grams), whereas it ranged from 2500 grams to 4500 grams with median (±IQR) of 3100 grams (±525 grams) among controls. Preterm birth (AOR = 5.32; CI = 2.959–9.567), history of any physical trauma experienced during pregnancy (AOR = 13.714; CI = 2.382–78.941), and history of any pregnancy complication (AOR = 2.708; CI = 1.634–4.487) were predictors of low birth weight. On the other hand, cesarean delivery (AOR = 0.415; CI = 0.183–0.941) and instrumental (AOR = 0.574; CI = 0.333–0.987) modes of delivery as well as maternal history of chronic diabetes (AOR = 0.275; CI = 0.090–0.836) had preventive effect of low birth weight.Conclusion. Preterm birth, history of experiencing any physical trauma during pregnancy, and history of any pregnancy complication were predictors of low birth weight, whereas cesarean and instrumental delivery had positive effect to preventing low birth weight.
Managing Emergencies in Rural North Queensland: The Feasibility of Teletraining
Authors: Pandit Tarsh , Ray Robin A. , Sabesan Sabe
Published: April 2018

Introduction. Historically, the use of videoconference technologies in emergency medicine training has been limited. Whilst there are anecdotal reports of the use of teletraining for emergency medicine by rural doctors in Australia, minimal evidence exists in the literature. This paper aimed to explore the use of teletraining in the context of managing emergency presentations in rural hospitals. Methods. Using a qualitative approach, a mixture of junior and senior doctors were invited to participate in semistructured interviews. Data were transcribed and analysed line by line. Applying the grounded theory principles of open and axial coding, themes and subthemes were generated. Results. A total of 20 interviews were conducted with rural doctors, rural doctors who are medical educators, and emergency medicine specialists. Two major themes—(1) teletraining as education and (2) personal considerations—and ten subthemes were evident from the data. Most participants had some previous experience with teletraining. Access to peer teaching over videoconference was requested by rural generalist registrars. There was a preference for interactive training sessions, over didactic lectures with little mention of technical barriers to engagement. The ability of teletraining to reduce professional isolation was a major benefit for doctors practicing in remote locations. Discussion. For these rural doctors, teletraining is a feasible method of education delivery. Wider application of teletraining such as its use in peer teaching needs to be explored. The benefits of teletraining suggest that teletraining models need to be core business for health services and training providers, including specialist colleges.
Interobserver Agreement in the Diagnosis of Inflammatory Bowel Disease-Associated Neoplasia in China in Comparison to Subspecialized American Gastrointestinal Pathologists
Authors: Wu Xian-rui , Liu Hua-shan , Shi Xue-ying , Zhou Wei-xun , Jiang Zhi-nong , Huang Yan , Karamchandani Dipti M. , Goldblum John R. , Xiao Shu-yuan , Zhu Hong-fa , Feely Michael M. , Collinsworth Amy L. , Esnakula Ashwini , Xie Hao , Shen Bo , Lan Ping , Liu Xiu-li
Published: April 2018

Background. The aim of this study was to evaluate the interobserver variability in diagnosing inflammatory bowel disease (IBD)-associated neoplasia among practicing pathologists from China using telepathology, a practice of remote diagnostic consultation increasingly used nationally and internationally, and its comparison with the interpretation of subspecialized gastrointestinal (GI) pathologists from the United States (US).Methods. Eight GI pathologists from the US and 4 pathologists from China with an interest in GI pathology participated in this study. A total of 50 colonic biopsies from patients with a clinical history of IBD from 8 medical centers in China were included. All microscopic slides in each case were digitized using an Aperio system. One pathologist (XL) reviewed the digitized full-slide images, and selected areas of interest were captured at low, medium, and high magnifications at a resolution of 1712 × 1072 pixels and saved as tagged image file format (TIFF) files on read-only DVD. Each pathologist evaluated the images and selected the most appropriate diagnostic category for each case (negative, indefinite, low-grade dysplasia [LGD], high-grade dysplasia [HGD], and carcinoma). A Fleiss’ kappa coefficient (K) analysis was performed to determine interobserver agreement and the agreement of each pathologist from China with the consensus diagnosis (defined as diagnostic agreement by at least 4 participating US GI pathologists).Results. There was substantial interobserver agreement among 4 pathologists from China on the interpretation of IBD-associated neoplasia (kappa value 0.68, 95% confidence interval: 0.56–0.78). A consensus diagnosis included negative (n=22), LGD (n=22), HGD (n=3), carcinoma (n=2), and indefinite for dysplasia (n=1). Using consensus diagnoses as references, the agreement between each pathologist from China and the consensus diagnosis was substantial with kappa values ranging from 0.75 to 0.80.Conclusions. This study reveals substantial interobserver agreement for the interpretation of colonic neoplasia in IBD using digitized images among Chinese pathologists as well as between each Chinese pathologist and a consensus diagnosis generated by US GI pathologists.
Electrocardiogram Changes of Donepezil Administration in Elderly Patients with Ischemic Heart Disease
Authors: Wang Deguo , Wu Yong , Wang Ancai , Chen Yueyun , Zhang Ting , Hu Nengwei
Published: April 2018

Objective. Donepezil, a widely used cholinesterase inhibitor for treating Alzheimer’s disease, has been reported to induce bradyarrhythmias and torsade de pointes. In this study, we aimed at determining electrocardiogram changes of donepezil administration in elderly patients with ischemic heart disease, who tend to suffer from cognitive disorders. Methods. Sixty patients with ischemic heart disease and mild cognitive impairment were treated with donepezil (5 mg/day) and followed up for at least four weeks. A twenty-four-hour ambulatory electrocardiogram was performed for the analysis of heart rate variability. The ECG parameters including heart rate (HR), PR and RR intervals, QT interval, and QRS duration were recorded at the baseline and after donepezil administration. Results. Donepezil administration resulted in significant reduction in mean HR and the lowest HR and prolongation of PR and RR intervals, whereas it had no significant effects on QRS duration and QT parameters including QT, corrected QT interval, QT dispersion, and Tpeak-end interval. HRV analysis showed that donepezil administration significantly improved parasympathetic function, indicated by decreased low/high frequency (LF/HF) ratio and high frequency (HF) components and oscillation of RR intervals. Conclusions. These data demonstrated that donepezil administration decreased HR, prolonged PR interval, and increased parasympathetic function without affecting QRS duration and QT intervals, suggesting that it can be used safely in elderly patients with ischemic heart disease.
Diethylnitrosamine Increases Proliferation in Early Stages of Hepatic Carcinogenesis in Insulin-Treated Type 1 Diabetic Mice
Authors: Arboatti A. S. , Lambertucci F. , Sedlmeier M. G. , Pisani G. , Monti J. , Álvarez M. de L. , Francés D. E. A. , Ronco M. T. , Carnovale C. E.
Published: April 2018

Diethylnitrosamine (DEN) induces hepatocarcinogenesis, increasing mitotic hepatocytes and leading to chronic inflammation. In addition, type 1 diabetes mellitus (T1DM) is also characterized by a proinflammatory state and by requiring insulin exogenous treatment. Given the association of diabetes, insulin treatment, and cell proliferation, our specific goal was to determine whether the liver in the diabetic state presents a greater response to DEN-induced cell cycle alteration, which is essential for the malignant transformation. Male C57BL/6 mice (four-week-old) were divided into 4 groups: C, C + DEN, T1DM, and T1DM + DEN. Mice were euthanized ten weeks after DEN injection. DEN per se produced an increase in liver lipid peroxidation levels. Besides, in T1DM + DEN, we found a greater increase in the proliferation index, in comparison with C + DEN. These results are in agreement with the increased expression observed in cell cycle progression markers: cyclin D1 and E1. In addition, a proapoptotic factor, such as activated caspase-3, evidenced a decrease in T1DM + DEN, while the Vascular Endothelial Growth Factor (VEGF) and the protooncogene p53 showed a higher increase with respect to C + DEN. Overall, the results allow us to highlight a major DEN response in T1DM, which may explain in part the greater predisposition to the development of hepatocarcinoma (HCC) during the diabetic state.
A Model of Overall Survival Predicts Treatment Outcomes with Atezolizumab versus Chemotherapy in Non–Small Cell Lung Cancer Based on Early Tumor Kinetics
Authors: Claret Laurent , Jin Jin Y. , Ferté Charles , Winter Helen , Girish Sandhya , Stroh Mark , He Pei , Ballinger Marcus , Sandler Alan , Joshi Amita , Rittmeyer Achim , Gandara David , Soria Jean-Charles , Bruno René
Published: April 2018

Purpose: Standard endpoints often poorly predict overall survival (OS) with immunotherapies. We investigated the predictive performance of model-based tumor growth inhibition (TGI) metrics using data from atezolizumab clinical trials in patients with non–small cell lung cancer.

Patients and Methods: OS benefit with atezolizumab versus docetaxel was observed in both POPLAR (phase II) and OAK (phase III), although progression-free survival was similar between arms. A multivariate model linking baseline patient characteristics and on-treatment tumor growth rate constant (KG), estimated using time profiles of sum of longest diameters (RECIST 1.1) to OS, was developed using POPLAR data. The model was evaluated to predict OAK outcome based on estimated KG at TGI data cutoffs ranging from 10 to 122 weeks.

Results: In POPLAR, TGI profiles in both arms crossed at 25 weeks, with more shrinkage with docetaxel and slower KG with atezolizumab. A log-normal OS model, with albumin and number of metastatic sites as independent prognostic factors and estimated KG, predicted OS HR in subpopulations of patients with varying baseline PD-L1 expression in both POPLAR and OAK: model-predicted OAK HR (95% prediction interval), 0.73 (0.63–0.85), versus 0.73 observed. The POPLAR OS model predicted greater than 97% chance of success of OAK (significant OS HR, P < 0.05) from the 40-week data cutoff onward with 50% of the total number of tumor assessments when a successful study was predicted from 70 weeks onward based on observed OS.

Conclusions: KG has potential as a model-based early endpoint to inform decisions in cancer immunotherapy studies. Clin Cancer Res; 24(14); 3292–8. ©2018 AACR.
Cycling Toward Progress: Ribociclib, a CDK 4/6 Inhibitor for Breast Cancer
Authors: Spring Laura , Bardia Aditya
Published: April 2018

Ribociclib is an orally active, highly selective inhibitor of cyclin-dependent kinase (CDK) 4 and 6. It is the second CDK 4/6 inhibitor approved for hormone receptor–positive breast cancer. The addition of ribociclib to an aromatase inhibitor has resulted in marked improvements in progression-free survival for patients with metastatic breast cancer. Clin Cancer Res; 24(13); 2981–3. ©2018 AACR.

See related article by Shah et al., p. 2999
Diálogo entre Literatura e Cinema: Narrativas de terror - o estudo de estratégias narrativas para “ancorar o efeito do real” na linguagem literária e na linguagem cinematográfica.
Authors: Nicolini Patrícia Peres Ferreira , Martins Analice de Oliveira
Published: April 2018

O artigo tem por objetivo compartilhar uma experiência bem sucedida de aulas de leitura trabalhando o “gênero narrativo terror” nas séries finais do Ensino Fundamental II. Nessas aulas, os alunos são convidados a analisar o gênero terror na linguagem literária e na linguagem cinematográfica buscando verificar as estratégias narrativas utilizadas por esse gênero para criar verossimilhança, aumento de expectativa do leitor e o clima de suspense. A constituição dessa proposta se baseou nos estudos de Tzvetan Todorov.
O imaginário medieval na literatura e no cinema: Reflexões acerca das obras O Senhor dos Anéis e As Crônicas de Nárnia
Authors: Bueno Rodrigo Poreli Moura
Published: April 2018

O tema do imaginário medieval na história e nas artes literária e cinematográfica está fortemente ligado às noções de maravilhoso e de fantasia. Percebemos que nas obras: “O Senhor dos Anéis” (1954) de J.R.R. Tolkien e “As Crônicas de Nárnia” (1950-1956) de C.S. Lewis, a Idade Média não é apenas considerado como pano de fundo para o desenrolar de suas narrativas. Há a tentativa de recriar os pactos sociais medievais, bem como os códigos de honra e valores cavalheirescos de uma época, envoltos em uma atmosfera mágica e fantástica, com elementos mitológicos e sobrenaturais, animais falantes e magia. Com base nestas considerações, procuramos ainda mostrar como as artes literária e fílmica dialogam com as ciências humanas e o modo dessas artes expressarem a cultura e a sociedade de diferentes épocas e lugares.
Paisagem, de Lygia Bojunga, na interface com o fantástico
Authors: Perim Regina Silva Michelli
Published: April 2018

O objetivo desse artigo é apresentar uma análise do livro Paisagem, escrito por Lygia Bojunga, no âmbito do fantástico, utilizando os conceitos de fantástico contemporâneo, autoficção e mise en abyme.
“My evil, and my lusty little heart”: Tradução intersemiótica de “The Tyger”, de William Blake, em “The Tale Of The Body Thief”, de Anne Rice
Authors: Santos Andrio J. R. dos
Published: April 2018

O presente trabalho visa analisar criticamente a operação de tradução intersemiótica do poema The Tyger, de William Blake, no romance The Tale Of The Body Thief, de Anne Rice. Para tal, empregam-se concepções teóricas propostas por autores como Diniz (1998), Clüver (2006) e Plaza (2008), que compreendem tradução intersemiótica essencialmente como um diálogo de significados intermídia em um processo de produção de sentido sempre em expansão.
La ficción y lo fantástico: entrevista con David Roas
Authors: García Flavio , Gama-Khalil Marisa Martins
Published: April 2018

Entrevista con David Roas.
“Devemos nos esforçar para comunir, porque temos padrões tão diferentes de lucidar”: os aspectos dialetais na linguagem de woman on the edge of time, de marge piercy
Authors: Furnaletto Elton
Published: April 2018

O presente artigo tem o objetivo de contribuir com os Estudos da Tradução na área da tradução de ficção científica no Brasil. O que se propõe apresentar são as particularidades do gênero no que diz respeito à construção de um mundo novo e o estabelecimento de algum tipo de mediação de linguagem com efeitos de discutir relações entre língua e sociedade. Utilizando-se dos conceitos de singularização (foregrounding) (LEECH, 1969), da estilística (MANDALA, 2010), e da tematização afetiva (STOCKWELL, 2000), vamos demonstrar como o romance Woman on the Edge of Time, de Marge Piercy, cria algumas variantes do inglês padrão contemporâneo, em diversos níveis de linguagem: fonológico, morfológico, sintático e semântico-pragmático. Para dar conta de traduzir essas marcações estilísticas, vamos lançar mão das teorias de tradução de dialetos (CARVALHO, 2017; BEREZOWSKI, 1997), os quais representam uma forma de marcar/singularizar o discurso. Esse artigo é um dos estudos que embasam a prática tradução do romance, em progresso.
Age- and Sex-Specific Reference Values for Media/Lumen Ratio in Small Arteries and Relationship With Risk Factors
Authors: Bruno Rosa Maria , Grassi Guido , Seravalle Gino , Savoia Carmine , Rizzoni Damiano , Virdis Agostino
Published: April 2018

Small-artery remodeling is an early feature of target organ damage in hypertension and retains a negative prognostic value. The aim of the study is to establish age- and sex-specific reference values for media/lumen in small arteries obtained in humans by biopsy. Data from 91 healthy individuals and 200 individuals with cardiovascular risk factors in primary prevention from 4 Italian centers were pooled. Sex-specific equations for media/lumen in the healthy subpopulation, with age as dependent variable, were calculated. These equations were used to calculate predicted media/lumen values in individuals with risk factors and
Z
scores. The association between classical risk factors and
Z
scores was then explored by multiple regression analysis. A second-degree polynomial equation model was chosen to obtain sex-specific equations for media/lumen, with age as dependent variable. In the population with risk factors (111 men, age 50.5±14.0 years, hypertension 80.5%), media/lumen
Z
scores were independently associated with body mass index (standardized β=0.293,
P
=0.0001), total cholesterol (β=0.191,
P
=0.031), current smoking (β=0.238,
P
=0.0005), fasting blood glucose (β=0.204,
P
=0.003), systolic blood pressure (β=0.233,
P
=0.023), and female sex (β=0.799,
P
=0.038). A significant interaction between female sex and total cholesterol was found (β=−0.979,
P
=0.014). Results were substantially similar in the hypertensive subgroup. A method to calculate individual values of remodeling and growth index based on reference values was also presented. Age- and sex-specific percentiles of media/lumen in a healthy population were estimated. In a predominantly hypertensive population, media/lumen
Z
scores were associated with major cardiovascular risk factors, including body mass index, cholesterol, smoking, glucose, and systolic blood pressure. Significant sex differences were observed.
Biological Sex Modulates the Adrenal and Blood Pressure Responses to Angiotensin II
Authors: Shukri Mohammad Zaki , Tan Jia Wei , Manosroi Worapaka , Pojoga Luminita H. , Rivera Alicia , Williams Jonathan S. , Seely Ellen W. , Adler Gail K. , Jaffe Iris Z. , Karas Richard H. , Williams Gordon H. , Romero Jose R.
Published: April 2018

The relationship between biological sex and aldosterone on blood pressure (BP) is unclear. We hypothesized that sex would modify the interaction between aldosterone and vascular responses to salt intake and angiotensin II (AngII). To test this hypothesis, in 1592 subjects from the well-controlled Hypertensive Pathotype cohort, we compared responses of women and men to chronic (BP and aldosterone levels in response to dietary salt) and acute (BP, renal plasma flow, and aldosterone responses to AngII infusion) manipulations. Women had a 30% higher salt sensitivity of BP than men (
P
<0.0005) regardless of age or hypertension status, a greater BP response to AngII, and a 15% greater aldosterone response to AngII on both restricted and liberal salt diets (
P
<0.005). Furthermore, there was an interaction (
P
=0.003) between sex and aldosterone on BP response to AngII. Women also had a greater (
P
<0.01) increment in renal plasma flow in response to AngII than men. To assess potential mechanisms for this sex effect, we compared aldosterone responses to AngII or potassium from rat zona glomerulosa cells and observed greater aldosterone production in female than male zona glomerulosa cells basally and in response to both agonists (
P
<0.0001). In a rodent model of aldosterone-mediated cardiovascular disease induced by increased AngII and low NO, circulating aldosterone levels (
P
<0.01), myocardial damage (
P
<0.001), and proteinuria (
P
<0.05) were greater in female than male rats despite having similar BP responses. Thus, increased aldosterone production likely contributes to sex differences in cardiovascular disease, suggesting that women may be more responsive to mineralocorticoid receptor blockade than men.
Favorable Modifiable Cardiovascular Risk Profile Is Associated With Lower Healthcare Costs Among Cancer Patients: The 2012–2013 Medical Expenditure Panel Survey
Authors: Singh Jai , Valero‐Elizondo Javier , Salami Joseph A. , Warraich Haider J. , Ogunmoroti Oluseye , Spatz Erica S. , Desai Nihar , Rana Jamal S. , Virani Salim S. , Blankstein Ron , Blaha Michael J. , Nasir Khurram
Published: April 2018

Background

Atherosclerotic cardiovascular disease (
ASCVD
) and cancer are among the leading causes of economic burden, morbidity, and mortality in the United States. We aimed to quantify the overall impact of cardiovascular modifiable risk factor (
CRF
) profile on healthcare expenditures among those with and without
ASCVD
and/or cancer.

Methods and Results

The 2012–2013 Medical Expenditure Panel Survey, a nationally representative adult sample (≥40 years), was utilized for the study. Variables included
ASCVD
,
CRF
(hypertension, diabetes mellitus, hypercholesterolemia, smoking, physical activity and/or obesity), and cancer (all). Two‐part econometric models analyzed cost data. Medical Expenditure Panel Survey participants (n=27 275, 59±9 years, 52% female) were studied and 14% had cancer, translating to 25.6 million
US
adults over 40 years of age. A higher prevalence of
ASCVD
was noted in those with versus without cancer (25% versus 14%). Absence of
ASCVD
and a more favorable
CRF
profile were associated with significantly lower expenditures across the spectrum of cancer diagnosis. Among cancer patients, the adjusted mean annual cost for those with and without
ASCVD
were $10 852 (95% confidence interval [8917, 12 788]) and $6436 (95% confidence interval [5531, 7342]). Among cancer patients without
ASCVD
, adjusted annual healthcare expenditures among those with optimal versus poor
CRF
profile were $4782 and $7256.

Conclusions

In a nationally representative
US
adult population, absence of
ASCVD
and a favorable
CRF
profile were associated with significantly lower medical expenditure among cancer patients. This provides estimates to continue better cardiovascular management and prevention practices, while contextualizing the burden of cancer.
10‐Year Associations Between Tumor Necrosis Factor Receptors 1 and 2 and Cardiovascular Events in Patients With Stable Coronary Heart Disease: A CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) Trial Substudy
Authors: Carlsson Axel C. , Ruge Toralph , Kjøller Erik , Hilden Jørgen , Kolmos Hans Jørn , Sajadieh Ahmad , Kastrup Jens , Jensen Gorm Boje , Larsson Anders , Nowak Christoph , Jakobsen Janus Christian , Winkel Per , Gluud Christian , Ärnlöv Johan
Published: April 2018

Background

We aimed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)‐α (TNFR1 and TNFR2) and cardiovascular outcomes in patients with stable coronary heart disease.

Methods and Results

CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) is a randomized clinical trial comparing clarithromycin with placebo in patients with stable coronary heart disease. The primary outcome was a composite of nonfatal acute myocardial infarction, unstable angina pectoris, cerebrovascular disease, and all‐cause mortality. Patients were followed up for 10 years; discovery sample, those assigned placebo (1204 events in n=1998); and replication sample, those assigned clarithromycin (1220 events in n=1979). We used Cox regression adjusted for C‐reactive protein level, established cardiovascular risk factors, kidney function, and cardiovascular drugs. After adjustments, higher serum levels of
TNFR
1 and
TNFR
2 were associated with the composite outcome in the discovery sample (hazard ratio per SD increase, 1.13; 95% confidence interval, 1.05–1.22;
P
=0.001 for
TNFR
1; hazard ratio, 1.16; 95% confidence interval, 1.08–1.24;
P
<0.001 for
TNFR
2). The associations were similar in the replication sample. The associations with the composite outcome were mainly driven by acute myocardial infarction, cardiovascular mortality, and noncardiovascular mortality. The addition of
TNFR
1 and
TNFR
2 to established cardiovascular risk factors improved prediction only modestly (<1%).

Conclusions

Increased concentrations of circulating
TNFR
1 and
TNFR
2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease. Yet, the utility of measuring
TNFR
1 and
TNFR
2 to improve risk prediction in these patients appears limited.

Clinical Trial Registration

URL:
https://www.clinicaltrials.gov
. Unique identifier:
NCT
00121550.
Beneficial Role of Neutrophils Through Function of Lactoferrin After Intracerebral Hemorrhage
Authors: Zhao Xiurong , Ting Shun-Ming , Sun Guanghua , Roy-O’Reilly Meaghan , Mobley Alexis S. , Bautista Garrido Jesus , Zheng Xueping , Obertas Lidiya , Jung Joo Eun , Kruzel Marian , Aronowski Jaroslaw
Published: April 2018

Background and Purpose—

Intracerebral hemorrhage (ICH) is a devastating disease with a 30-day mortality of ~50%. There are no effective therapies for ICH. ICH results in brain damage in 2 major ways: through the mechanical forces of extravasated blood and then through toxicity of the intraparenchymal blood components including hemoglobin/iron. LTF (lactoferrin) is an iron-binding protein, uniquely abundant in polymorphonuclear neutrophils (PMNs). After ICH, circulating blood PMNs enter the ICH-afflicted brain where they release LTF. By virtue of sequestrating iron, LTF may contribute to hematoma detoxification.

Methods—

ICH in mice was produced using intrastriatal autologous blood injection. PMNs were depleted with intraperitoneal administration of anti-Ly-6G antibody. Treatment of mouse brain cell cultures with lysed RBC or iron was used as in vitro model of ICH.

Results—

LTF mRNA was undetectable in the mouse brain, even after ICH. Unlike mRNA, LTF protein increased in ICH-affected hemispheres by 6 hours, peaked at 24 to 72 hours, and remained elevated for at least a week after ICH. At the single cell level, LTF was detected in PMNs in the hematoma-affected brain at all time points after ICH. We also found elevated LTF in the plasma after ICH, with a temporal profile similar to LTF changes in the brain. Importantly, mrLTF (recombinant mouse LTF) reduced the cytotoxicity of lysed RBC and FeCl
3
to brain cells in culture. Ultimately, in an ICH model, systemic administration of mrLTF (at 3, 24, and 48 hours after ICH) reduced brain edema and ameliorated neurological deficits caused by ICH. mrLTF retained the benefit in reducing behavioral deficit even with 24-hour treatment delay. Interestingly, systemic depletion of PMNs at 24 hours after ICH worsened neurological deficits, suggesting that PMN infiltration into the brain at later stages after ICH could be a beneficial response.

Conclusions—

LTF delivered to the ICH-affected brain by infiltrating PMNs may assist in hematoma detoxification and represent a powerful potential target for the treatment of ICH.
Coat Color of Shelter Dogs and Its Role in Dog Adoption
Authors: Voslarova Eva , Zak Jiri , Vecerek Vladimir , Bedanova Iveta
Published: April 2018

Coat color influenced the likelihood of a dog being reclaimed from a shelter as well as the length of stay (LOS) of abandoned dogs at the shelter. The shortestLOSwas found in brindle and multicolor dogs (median time until adoption: 17 and 18 days, respectively) followed by white, fawn, red, brown, black and tan, and grey dogs. Black dogs had the greatestLOS(median 32 days). In lost dogs, coat color had no significant effect on the time spent at a shelter, the median time until a dog was reclaimed by his/her caretaker being one day, irrespective of the coat color. However, the results of our study suggest that black, brown, and brindle dogs are more likely to be abandoned by their caretakers, and that fawn, black and tan, grey, and red dogs, if lost, have a better chance of being reclaimed by their caretakers.
Promoting Technology Transfers in Nigeria’s Extractive Industries: A Review of the Legal Regime, the Challenges and Proposals for Responses
Authors: Orji Uchenna Jerome
Published: April 2018

The need to bridge the technological gap between developed and developing countries have remained a major topic in the arena of international economic policy over the last fifty years. In this respect, the critical role of technology transfers in facilitating the development of developing countries has continued to receive international attention. However, many developing countries have also taken their own paths to promote technology transfers in critical economic sectors by establishing enabling legal and policy measures with the aim of fostering economic development through that process. This article examines the legal regime for promoting and regulating technology transfers in Nigeria’s extractive industries and highlights some of its drawbacks. The article also examines other peculiar challenges hindering technology transfers in Nigeria’s extractive industries and proposes legal and policy measures to address those challenges.
Filling the gap of whip spider distribution in Asia: Phrynichus persicus sp.n. (Arachnida, Amblypygi), a new Phrynichidae from Iran
Authors: DE MIRANDA GUSTAVO SILVA , ZAMANI ALIREZA
Published: April 2018

The whip spider genus Phrynichus (Phrynichidae, Amblypygi) is widely distributed in Africa, the Arabian Peninsula and Asia with a total of 17 species. No records, however, are known from several countries in the Middle East. Here we provide the first record of a whip spider from Iran (Ilam Province), with the description and illustration of a new species, Phrynichus persicus sp. n. This discovery fills a gap in the distribution of the group that is known from both sides of this biogeographically interesting region and is also the northernmost record of the family Phrynichidae. Moreover, all distribution records of the Phrynichus species are mapped (including the first verified record of the order from the United Arab Emirates), an updated key to the species of the deflersi and ceylonicus groups is provided, and Phrynichus andhraensis Bastawade, Rao, Maqsood Javed and Krishna, 2005 (India) is assigned to the ceylonicus group.
The Latin stranger-science, or l’anthropologie among the Lusitanians
Authors: Roque Ricardo
Published: April 2018

This essay traces the connected histories of Portuguese and French anthropology in the late nineteenth century. By looking at a Portuguese scientific institution, the Carlos Ribeiro Society, it considers how French race science, known as anthropologie, was adopted and adapted across the European Latin world as a type of “stranger-science.” That is: as an authoritative outsider scientific formation, installed into national terrain in accordance with insider strategies for turning foreign elements into native forms of scientific sovereignty and modernity. French anthropology’s international diffusion becomes meaningful in the light of the Portuguese incorporating what was foreign and modern as a means to generate vitality, and authority endogenously in their own national context. Hence, addressing the circulation of stranger-sciences can pave the way for an original conceptualizing of the transnational life of race science across and even beyond the Latin world.
Efficacy of Video Modeling and Brief Coaching on Teacher Implementation of an Evidence-Based Practice for Students With Severe Disabilities
Authors: Brock Matthew E. , Seaman Rachel L. , Gatsch Andrea L.
Published: April 2018

Effective professional development strategies are needed to enable special educators to provide evidence-based instruction and support to students with severe disabilities. In this single-case design study, we measured the efficacy of video modeling and brief coaching to enable three elementary special education teachers to implement constant time delay and the impact of their implementation on student progress toward individualized goals. After receiving professional development, all three teachers implemented constant time delay with fidelity and promoted student progress on individualized goals. Teachers were able to identify and correct some of their own implementation errors by revisiting video models after attempting implementation. Teachers reported positive perceptions of the professional development model. We provide recommendations for how video modeling and brief coaching can be used in tandem to promote effective implementation of evidence-based practices.
Toxicologic Pathology Forum Opinion Paper: Considerations for Toxicologic Pathologists Evaluating the Safety of Biomaterials and Finished Medical Devices
Authors: Gad Shayne C. , Schuh JoAnn C. L.
Published: April 2018

Safety (“biocompatibility”) assessment of medical devices has evolved along a different path than that of drugs, being historically governed more by the considerations and needs of engineers rather than chemists and biologists. As a result, the involvement of veterinary pathologists has been much more limited—almost entirely to evaluating tissue responses in tissues in direct contact with implanted devices. As devices have become more complex in composition, structure, placement, and use, concerns as to adverse systemic responses in patients have called for more comprehensive and thoughtful evaluations of effects throughout the body. Further complexities arise from the increasing marriage of devices and drug/biologic therapeutics to achieve either better dose control and, specifically, in delivery to target organs/tissues or better tolerance of the body to medical devices (i.e., minimization of the foreign body response). The challenge to pathologists is to integrate in new technologies (such as in vivo imaging and immunology) and ways of viewing interactions with patient bodies. To fail to do so will allow the methods and standards for medical device safety evaluation to be based on chemical analysis and then the limited details inherent in literature-based risk assessments.
Ret Oncogene Protein Expression in Papillary Thyroid Carcinoma and Related Lesions
Authors: Mai Kien T , Landry Denise C , Thomas Jane , Yazdi Hossein M , Perkins D Garth , Odell Paul F
Published: April 2018

Background

Activation of Ret oncogenes, particularly Ret/PTC, has been identified in papillary thyroid carcinoma (PTC). The purpose of this study was to investigate the immunostaining pattern of Ret oncogene protein in PTC and nodular non-PTC lesions with a fine chromatin pattern.

Materials and Methods

Ninety-three PTC and 139 nodular non-PTC lesions were microscopically reviewed to identify the nuclear changes of “limited nuclear features of PTC” (focal nuclear grooves, nuclear inclusions or optically clear nuclei) and areas of infiltrating carcinoma (IC) and were submitted for immunostaining with Ret oncogene protein antiserum.

Results

Immunoreactivity for Ret protein ranged from negative in follicular adenoma (FA) with a coarse chromatin pattern, to negative or weak reactivity in FA with a fine chromatin pattern, to strong reactivity in PTC with areas of infiltrating carcinoma (IC). In FA with fine chromatin, FA and follicular carcinoma (FC) containing an admixture of areas of coarse and fine chromatin, areas with nuclear changes with “limited nuclear features of PTC” displayed varying degrees of immunoreactivity. The intensity of immunostaining varied with the degree of nuclear change. The noninvasive component of PTC with IC usually showed more extensive and stronger reactivity than PTC without IC. PTCs with and without IC were associated with a rate of lymph node metastasis of 48% and 3%, respectively.

Conclusions

The expression of Ret oncogenes (Ret/PTC, other unknown variants or wild type) is focally or extensively present in all PTC with IC. The degree of immunoreactivity is likely to be proportional to the potential for lymph node metastasis of PTC. In the context of this study and due to the specificity of Ret oncogenes, it is likely that nodular non-PTC lesions with a fine chromatin pattern and focal positive reactivity for Ret oncogene represent PTC-related lesions.
Abdominal and Pelvic Ct for Detection and Volume Assessment of Peritoneal Sarcomatosis
Authors: Pestieau Sophie R , Jelinek James S , Sugarbaker Paul H
Published: April 2018

Objective

Peritoneal sarcomatosis is a common finding in patients with recurrent abdominal or pelvic sarcoma. CT of the abdomen and pelvis is the standard radiological examination for evaluation of tumor volume and location in the peritoneal cavity; however data regarding the reliability of recurrent sarcoma detection has not been available. The purpose of this study was to evaluate the sensitivity of CT in detecting recurrent peritoneal sarcomatosis.

Methods

Abdominal and pelvic CT scans of 33 patients with abdominal or pelvic sarcoma recurrence were retrospectively reviewed. Subsequently all patients underwent surgery at which time complete exploration of the abdomen and pelvis was performed. Twenty-five CT parameters were evaluated and statistically analyzed using the findings at surgery as a standard.

Results

Among the anatomic sites, the lesser omentum and the Douglas pouch showed a sensitivity of 100%. In the nine abdominopelvic regions sensitivity was greater than 85% in the central region, the left lower quadrant and the pelvis. In all regions and sites, the pelvis and Douglas pouch showed the highest accuracy (91%). The volume of tumor present within an abdominopelvic region influenced the sensitivity. A sensitivity of 72.5% was recorded when tumor nodules were less than 0.5 cm in diameter. This increased to 90% when tumor diameter was greater than 5 cm.

Conclusions

Abdominal and pelvic CT is a reliable test to evaluate recurrent sarcoma. The nodules in the pelvis were most accurately detected. Even small nodules of 0.5 cm were detected; the sensitivity increased as the nodules became greater than 5 cm.