bluuebunny/crossref_metadata_2025 huggingface dataset:
Black tea extract and theaflavin derivatives affect the pharmacokinetics of rosuvastatin by modulating organic anion transporting polypeptide (OATP) 2B1 activity
Authors: Kondo Ayuko , Narumi Katsuya , Okuhara Keisuke , Takahashi Yuka , Furugen Ayako , Kobayashi Masaki , Iseki Ken
Published: August 2019

Theaflavins (TFs) are derived from black tea, an important source of dietary polyphenols. Although the potential interactions between dietary polyphenols and drugs have been demonstrated through in vitro and in vivo studies, little information is available concerning the influence of TFs on drug disposition. Organic anion transporting polypeptide 2B1 (OATP2B1) is expressed in human enterocytes and plays a role in the intestinal absorption of numerous drugs. The current study evaluated the effects of black tea extracts on the pharmacokinetics of rosuvastatin in rats, and investigated the effect of four major TFs (theaflavin, theaflavin‐3‐gallate, theaflavin‐3′‐gallate and theaflavin‐3,3′‐digallate) on the transport activity of OATP2B1. Black tea extracts significantly decreased the maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC0–8) of rosuvastatin by 48% and 37%, respectively (p < 0.001 and p < 0.01, respectively). Moreover, OATP2B1‐mediated rosuvastatin and estrone‐3‐sulfate uptake was significantly reduced in the presence of TFs. A kinetic study revealed that the uptake efficiency (in terms of Vmax/Km) of rosuvastatin was decreased following treatment with TFs. Black tea extracts also reduced OATP2B1‐mediated rosuvastatin uptake. These results suggest that black tea reduces the plasma concentrations of rosuvastatin by inhibiting the intestinal OATP2B1‐mediated transport of rosuvastatin.
Developmental toxicity of e‐cigarette aerosols
Authors: Greene Robert M. , Pisano M. Michele
Published: August 2019

Maternal smoking during pregnancy represents a major public health concern increasing the risk for low birth weight, congenital anomalies, preterm birth, fetal mortality, and morbidity. In an effort to diminish adverse developmental effects of exposure to cigarette smoking, pregnant women, and women of reproductive age, are increasingly turning to electronic nicotine delivery systems (ENDS), such as e‐cigarettes, as an alternative. Given that health risks associated with ENDS use during pregnancy are largely unknown, there is an acute need to determine risks vs. benefits of e‐cigarette use by pregnant women. While the most recent Surgeon General's Report on the “Health Consequences of Smoking” states that “the evidence is sufficient to infer that nicotine adversely affects maternal and fetal health during pregnancy, contributing to multiple adverse outcomes,” it remains unclear whether use of ENDS represents a “safer alternative” to tobacco smoking during pregnancy. This is due, in part, to the lack of sufficient and conclusive evidence concerning whether or not maternal e‐cigarette use adversely affects embryonic/fetal development. While several recent developmental studies have challenged the safety of nicotine inhalation via ENDS, the true risks of smoking e‐cigarettes during the first trimester of pregnancy—the period of organogenesis—are largely unknown. Moreover, evidence is emerging that even nicotine‐free e‐cigarette aerosols may harm the developing conceptus, suggesting that components of e‐cigarette liquid, including flavorings, may be developmentally toxicity. Focused human epidemiological analyses, and carefully designed animal studies are critically needed to address the question of the safety of ENDS use during pregnancy.
Paraoxonase 1 and atherosclerosis‐related diseases
Authors: Kotur‐Stevuljević Jelena , Vekić Jelena , Stefanović Aleksandra , Zeljković Aleksandra , Ninić Ana , Ivanišević Jasmina , Miljković Milica , Sopić Miron , Munjas Jelena , Mihajlović Marija , Spasić Slavica , Jelić‐Ivanović Zorana , Spasojević‐Kalimanovska Vesna
Published: August 2019

A direct and an indirect relationship between paraoxonase 1 (PON1) and atherosclerosis exists. Given PON1's physical location within high‐density lipoprotein (HDL) particles and its recognized enzyme activity, it is certainly reasonable to suggest that PON1 facilitates the antiatherogenic nature of HDL particles. PON1 also plays a role in regulating reverse cholesterol transport, antioxidative, anti‐inflammatory, antiapoptotic, vasodilative, and antithrombotic activities and several endothelial cell functions. HDL dysfunctionality is a more recent issue and seems to be centered on pathological conditions affecting HDL structure and size profiles. This review is focused on the role of PON1 status in different atherosclerosis‐related diseases that we have studied over the last twenty years (coronary heart disease, acute ischemic stroke, diabetes mellitus type 2, end‐stage renal disease, chronic obstructive pulmonary disease, and sarcoidosis) with the aim to determine the true value of PON1 as a biomarker. The role of PON1 in cancer is also covered, as risk factors and mechanisms underlying both atherosclerosis and cancer share common features.
Chiral Resolution of Racemic 2‐Pyrone Diels‐Alder Cycloadduct by Diastereomeric Salt Formation
Authors: Jeon Tae‐Hong , Kang Hyung‐Joon , Svirid Anastasia , Lyakhov Alexander , Kovalenko Vitaly , Cho Cheon‐Gyu
Published: August 2019

An efficient protocol was developed that allows resolution of racemic bicyclolactone carboxylic acid obtained from the Diels‐Alder cycloaddition of 3,5‐dibromo‐2‐pyrone by formation of diastereomeric salts with quinidine and cinchonidine.
“Triceps Brachii Muscle Response to Neurostimulation of the Radial Nerve during Axillary Plexus Blockade: Clinical, Anatomical and Histological Correlation”
Authors: Ruiz Carlos , Varela Víctor , Sala‐Blanch Xavier , Martínez Adriana , Reina Miguel A.
Published: August 2019

Axillary plexus blockade is a common technique in clinical practice with a well‐known pattern of structures around the brachial artery. Historically, the only proper response to radial nerve stimulation was considered to be extension of the hand and wrist. Twenty‐five axillary blockades were assessed by ultrasound and neurostimulation; the principal objective was to correlate the needle position over the radial nerve with the anatomical and histological structure of that nerve. During the procedure, the needle was directed in two ways to reach the medial or lateral margin of the nerve: above the brachial artery or beneath it. Once the needle reached the nerve, the current was augmented gradually until a response was elicited. For the cadaveric anatomical study, eight axillae were dissected and histological samples were examined. The response of the triceps brachii muscle differed significantly between the two approaches to the radial nerve (P < 0.001), and the mean intensity of stimulation was significantly lower when the nerve was accessed above the artery (0.44 ± 0.15 mA) than below it (0.57 ± 0.17 mA) (P = 0.015). A triceps brachii motor response occurs at lower current intensity and lower needle‐nerve distance when the radial nerve is accessed above the artery and over the latissimus dorsi tendon. These findings were correlated with the topography of the radial nerve in the axillary fossa. Clin. Anat. 33:578–584, 2020. © 2019 Wiley Periodicals, Inc.
Estimating the optimal rate of adjuvant chemotherapy utilization for stage III colon cancer
Authors: Karim Safiya , Booth Christopher M. , Brennan Kelly , Peng Yingwei , Siemens D. Robert , Krzyzanowska Monika K. , Mackillop William J.
Published: August 2019

Background

Identifying optimal chemotherapy utilization rates can drive improvements in quality of care. We report a benchmarking approach to estimate the optimal rate of adjuvant chemotherapy (ACT) for stage III colon cancer.

Methods

The Ontario Cancer Registry and linked treated records were used to identify ACT utilization. Monte Carlo simulation was used to estimate the proportion of ACT rate variation that could be due to chance alone. The criterion‐based benchmarking approach was used to explore whether socioeconomic or system‐level factors were associated with ACT. We also used the “pared‐mean” approach to identify a benchmark population of hospitals with the highest ACT rates.

Results

The study population included 2801 patients; ACT was delivered to 66% (1861/2801). Monte Carlo simulation suggested that the observed component of variation (15.6%) in ACT rates was within the 95% CI (11.5%‐17.3%) of what could be expected due to chance alone; the nonrandom component of ACT rate variation across hospitals was only 1.5%. There was no difference in hospital ACT rate by teaching status (P = .107), cancer center status (P = .362), or having medical oncology on site (P = .840). Unadjusted ACT rates varied across hospitals (range 44%‐91%, P = .017). The unadjusted benchmark ACT rate was 81% (95%CI 76%‐86%); utilization rate in non‐benchmark hospitals was 65% (95%CI 63%‐66%). However, after adjusting for case mix, the difference in ACT utilization between benchmark and non‐benchmark populations was significantly smaller.

Conclusions

We did not find any system‐level factors associated with the utilization of ACT. Our results suggest that the observed variation in hospital ACT rate is not significantly different from variation due to chance alone. Using the “pared‐mean” approach may significantly overestimate optimal treatment rates if case mix is not considered.
Construction and validation of a nomogram to predict overall survival in patients with inflammatory breast cancer
Authors: Diao Jian‐dong , Ma Li‐xia , Sun Mei‐yang , Wu Chun‐jiao , Wang Li‐juan , Liu Yan‐ling , Yang Yong‐jing
Published: August 2019

In the present study, we examined the factors affecting survival of women with inflammatory breast cancer (IBC) and constructed and validated a nomogram to predict overall survival (OS) in these patients. The cohort was selected from the Surveillance, Epidemiology, and End Results (SEER) program between 1 January 2004 and 31 December 2013. Univariate and multivariate Cox proportional hazards regression models were constructed. A nomogram was developed based on significant prognostic indicators of OS. The discriminatory and predictive capacities of the nomogram were assessed using Harrell's concordance index (C‐index) and calibration plots. A total of 1651 eligible patients were identified, with a median survival time of 31 months (range 0‐131 months), and the 3‐ and 5‐year OS rates were 52.8% and 39.5%, respectively. Multivariate analysis revealed that race (P < .001), marital status (P = .011), N stage (P = .002), M stage (P < .001), hormone receptor (P < .001), human epidermal growth factor receptor‐2 (HER2) (P = .001), surgery (P < .001), chemotherapy (P < .001), and radiotherapy (P = .010) were independent prognostic indicators of IBC. These nine variables were incorporated to construct a nomogram. The C‐indexes of the nomogram were 0.738 (95% confidence interval [CI]: 0.717, 0.759) and 0.741 (95% CI: 0.717, 0.765) for the internal and external validations, respectively. The nomogram had a better discriminatory capacity for predicting OS than did the SEER summary stage (P < .001) or the American Joint Committee on Cancer tumor‐node metastasis staging systems (8th edition; P < .001). The calibration plot revealed satisfactory agreement between the findings and predicted outcomes in both the internal and external validations. The nomogram‐based 3‐ and 5‐year OS predictions for patients with IBC exhibited superior accuracy over the existing models.
Know how to manage office controversies
Authors: McCarthy Claudine
Published: August 2019

College athletics administrators learn a great deal of useful information during the years they invest in pursuing their own higher education. But you likely haven't taken a course in how to prepare for and manage controversies and scandals and the accompanying drama and upheaval. Fact is, that type of training would have immeasurable value that would unfortunately come in handy at many points during your career.
Differential influence of lesion length on fractional flow reserve in intermediate coronary lesions between each coronary artery
Authors: Shibutani Hiroki , Fujii Kenichi , Matsumura Koichiro , Otagaki Munemitsu , Morishita Shun , Bando Kazunori , Motohiro Masayuki , Umemura Shigeo , Shiojima Ichiro
Published: August 2019

Objectives

This study evaluated whether the influence of lesion length on functional significance is similar between each target artery.

Background

In the presence of a similar moderate degree of stenosis, the fractional flow reserve (FFR) in the left anterior descending coronary artery (LAD) is more often <0.80 than in the other arteries.

Methods

A total of 221 lesions with intermediate stenosis on coronary angiography that underwent FFR measurement for the evaluation of myocardial ischemia were enrolled. Quantitative coronary angiographic analysis including percent diameter stenosis and lesion length was performed. The area under the receiver operating characteristics (ROC) curve was estimated for the best cutoff value as a predictor of FFR value of ≤0.80 for each coronary artery.

Results

Although lesion length was similar among the lesions with an FFR >0.80 at different locations, the mean lesion length was significantly longer for lesions in the right coronary artery (RCA) with an FFR ≤0.80 than for those in the LAD and left circumflex artery (13.4 ± 3.4 vs. 8.6 ± 3.1 vs. 12.0 ± 3.7 mm, p < .001). ROC analysis demonstrated that the optimal cutoff value of lesion length for predicting an FFR ≤0.80 was 10.0 mm in the LAD (0.56 area under the curve [AUC], 48% sensitivity, and 76% specificity), whereas 13.1 mm in the RCA (0.84 AUC, 67% sensitivity, and 93% specificity).

Conclusions

The impact of lesion length on myocardial ischemia is different for each coronary artery. A longer lesion length is required in the RCA than in the LAD to achieve an FFR ≤0.80.
Differences in risk factors and resource utilization for women undergoing percutaneous coronary intervention and lower extremity peripheral vascular intervention
Authors: Doshi Rajkumar , Patel Krunalkumar , Desai Rupak , Patel Palakkumar , Grines Cindy , Meraj Perwaiz
Published: August 2019

Objective

To investigate the differences in risk factors and in‐hospital outcomes for women undergoing percutaneous coronary intervention (PCI) and peripheral vascular intervention (PVI).

Background

The clinical impact of coronary artery disease (CAD) and peripheral artery disease (PAD) is well characterized and is associated with high morbidity and mortality. There is lack of data comparing risk factors and in‐hospital outcomes for PCI and PVI, particularly in women.

Methods

Only female hospitalizations (age ≥ 18 years) who underwent PCI or PVI from 2005 to 2014 were identified using appropriate International Classification of Diseases‐Ninth Revision, Clinical Modification codes from the National Inpatient Sample database. Charlson's Comorbidity Index (CCI) was selected as the primary endpoint of the study. Coprimary endpoint was the cost of hospitalizations associated with PCI or PVI.

Results

Of the 2,461,328 female hospitalizations that were included, 85.6% (N = 2,105,236) underwent PCI and 14.4% (N = 356,092) received PVI. Compared to PCI, PVI hospitalizations were 3.2 years older (p < .001) and consisted of significantly more hospitalizations above 80 years of age (26.5% vs. 18.6%; p < .001). Hospitalizations with CCI ≥3 were significantly higher in the PVI cohort (29.1% vs. 24%; p < .001). CCI in women increased during the study period for both groups. PVI hospitalizations had a significantly longer length of stay (3 days vs. 2 days; p < .001) and cost of hospitalization ($23,610 vs. $20,571; p < .001), compared to PCI. Finally, the mean cost of hospitalizations increased during the study period for PCI and PVI.

Conclusion

Women hospitalized for PVI had a greater risk‐profile and resource utilization as demonstrated by the longer length of stay and higher cost compared to PCI.
An unusual shot‐retrograde transthoraco‐abdominal venous bullet embolization
Authors: Salahuddin Salman , Faizal Ali , Koshy Sudeep , Moideen Koya Muneer
Published: August 2019

A 72‐year‐old gentleman was brought to the emergency department, after sustaining an allegedly accidental airgun‐shot injury to the right side of his neck. A chest radiograph and plain CT chest revealed the bullet lodged deeply in the soft tissues of the right side of the neck. He was taken up for an emergency neck exploration for foreign body removal. Peroperatively, the bullet was observed to be lodged in the right internal jugular vein. During the attempt to retrieve the bullet, it inadvertently migrated downstream. An intraoperative fluoroscopy revealed the bullet in the thorax near the level of the diaphragm. A subsequent CT chest revealed an intracardiac location of the bullet in the right atrium, at its junction with the inferior vena cava. When it was decided to attempt a percutaneous endovascular retrieval strategy, fluoroscopic imaging of the chest in the cardiac catheterization lab, revealed that the bullet was no longer in the thorax, and had migrated again, and was found to be located in the left side of the pelvis. A subsequent venogram showed the bullet to be lodged in a tributary of the left external iliac vein. It was then snared percutaneously, through the left femoral vein, and delivered through a venotomy. Vascular bullet embolization is a rare phenomenon, especially, as in this case, a retrograde venous embolization with a transthoraco‐abdominal course. The treatment of bullet embolization, whether surgical or endovascular, depends on the final destination site, symptomatic status and propensity for complications.
Pulmonary artery‐focused contrast echocardiography with supplemental oxygen(PCESO) for echocardiographic diagnosis of anomalous origin of left coronary artery from pulmonary artery: Novel use of an old technique
Authors: Malakan Rad Elaheh , Aghaei‐Moghadam Ehsan , Mirzaaghayan Mohammad Reza , Pouraliakbar Hamid Reza
Published: August 2019

Pulmonary artery‐focused agitated saline contrast echocardiography unveils tricky cases of ALCAPA by the entry of microbubbles into the left coronary artery (LCA) during systole and retrograde flow from LCA into the main pulmonary artery during diastole. Associated pulmonary hypertension, if present, augments the former flow and supplemental oxygen increases the latter.
Calculation of risk costs in construction projects
Authors: Brokbals Stefanie , Wapelhorst Vincent , Čadež Ivan
Published: August 2019

As early as 1971, Schubert made a first contribution to the consideration of risks during the execution of construction projects. In addition to that, he was first to introduce elements of the risk management process to the construction management literature in Germany. By the use of an empirical study of the probability of risk occurrence and the cost amount by risk occurrence, Schubert made among others a statement about the importance of the risks depending on the amount of the risk costs. In an updated study for building construction projects with construction costs ≤2.5 million € and unit price contracts applying the VOB/B primarily the altered risk evaluations are shown; it needs to be emphasized that the sum of the determined risk costs corresponds to Schubert's results. Furthermore, with a variation of the characteristic attributes (response options) of the probability of risk occurrence and the cost amount by risk occurrence, it can be displayed that the risk costs during the execution of building construction projects are even considerably higher. Additionally, a probabilistic risk cost calculation — applying the Monte Carlo method — is used to reveal the bandwidth of risk costs. It can be pointed out that the risk costs range between 2.71% and 8.67% of the construction costs. The results could serve as a benchmark for contractors during the tender calculation to determine the amount of risk costs depending for example, on the market situation, the company‐specific risk disposition as well as strategic considerations.
Generation and Reaction of Functional Alkyllithiums by Using Microreactors and Their Application to Heterotelechelic Polymer Synthesis
Authors: Nagaki Aiichiro , Yamashita Hiroki , Tsuchihashi Yuta , Hirose Katsuyuki , Takumi Masahiro , Yoshida Jun‐ichi
Published: August 2019

Flow microreactors enabled the successful generation of various functional alkyllithiums containing electrophilic functional groups, as well as the use of these alkyllithiums in subsequent reactions. The high reactivity of these series of reactions could be achieved by the extremely accurate and selective control of residence time. Moreover, integrated flow microreactor systems could be used to successfully synthesize heterotelechelic polymers with two functionalities, one at each end, via a process involving controlled anionic polymerization initiated by functional alkyllithium compounds, followed by trapping reactions with difunctional electrophiles.
Efficient and Saturated Red Light‐Emitting Electrochemical Cells Based on Cationic Iridium(III) Complexes with EQE up to 9.4 %
Authors: Yu Guang‐Xiang , Lin Chien‐Hsiang , Liu You‐Xuan , Yi Rong‐Huei , Chen Guan‐Yu , Lu Chin‐Wei , Su Hai‐Ching
Published: August 2019

Solid‐state light‐emitting electrochemical cells (LECs) have several advantages, such as low‐voltage operation, compatibility with inert metal electrodes, large‐area flexible substrates, and simple solution‐processable device architectures. However, most of the studies on saturated red LECs show low or moderate device efficiencies (external quantum efficiency (EQE) <3.3 %). In this work, we demonstrate a series of five red‐emitting cationic iridium complexes (RED1‐‐RED5) with 2,2′‐biquinoline ligands and test their electroluminescence (EL) characteristics in LECs. The Commission Internationale de l′Eclairage (CIE) 1931 coordinates for the LECs based on these complexes are all beyond the National Television System Committee (NTSC) red standard point (0.67, 0.33). The maximal EQE of the neat‐film RED1‐based LECs reaches 7.4 %. The reddest complex, RED3, is doped in the blue‐emitting host complex, BG, to fabricate host–guest LECs. The maximal EQE of the host–guest LECs (1 wt % complex RED3) reaches 9.4 %, which is among the highest reported for the saturated red LECs.
On the importance of modeling balloon folding, pleating, and stent crimping: An FE study comparing experimental inflation tests
Authors: Geith Markus A. , Swidergal Krzysztof , Hochholdinger Bernd , Schratzenstaller Thomas G. , Wagner Marcus , Holzapfel Gerhard A.
Published: August 2019

Finite element (FE)–based studies of preoperative processes such as folding, pleating, and stent crimping with a comparison with experimental inflation tests are not yet available. Therefore, a novel workflow is presented in which residual stresses of balloon folding and pleating, as well as stent crimping, and the geometries of all contact partners were ultimately implemented in an FE code to simulate stent expansion by using an implicit solver. The numerical results demonstrate that the incorporation of residual stresses and strains experienced during the production step significantly increased the accuracy of the subsequent simulations, especially of the stent expansion model. During the preoperative processes, stresses inside the membrane and the stent material also reached a rather high level. Hence, there can be no presumption that balloon catheters or stents are undamaged before the actual surgery. The implementation of the realistic geometry, in particular the balloon tapers, and the blades of the process devices improved the simulation of the expansion mechanisms, such as dogboning, concave bending, or overexpansion of stent cells. This study shows that implicit solvers are able to precisely simulate the mentioned preoperative processes and the stent expansion procedure without a preceding manipulation of the simulation time or physical mass.
Biomechanical modeling and computer simulation of the brain during neurosurgery
Authors: Miller Karol , Joldes Grand R. , Bourantas George , Warfield Simon K. , Hyde Damon E. , Kikinis Ron , Wittek Adam
Published: August 2019

Computational biomechanics of the brain for neurosurgery is an emerging area of research recently gaining in importance and practical applications. This review paper presents the contributions of the Intelligent Systems for Medicine Laboratory and its collaborators to this field, discussing the modeling approaches adopted and the methods developed for obtaining the numerical solutions. We adopt a physics‐based modeling approach and describe the brain deformation in mechanical terms (such as displacements, strains, and stresses), which can be computed using a biomechanical model, by solving a continuum mechanics problem. We present our modeling approaches related to geometry creation, boundary conditions, loading, and material properties. From the point of view of solution methods, we advocate the use of fully nonlinear modeling approaches, capable of capturing very large deformations and nonlinear material behavior. We discuss finite element and meshless domain discretization, the use of the total Lagrangian formulation of continuum mechanics, and explicit time integration for solving both time‐accurate and steady‐state problems. We present the methods developed for handling contacts and for warping 3D medical images using the results of our simulations. We present two examples to showcase these methods: brain shift estimation for image registration and brain deformation computation for neuronavigation in epilepsy treatment.
Intersubject and Intrasubject Variability of Potential Plasma and Urine Metabolite and Protein Biomarkers in Healthy Human Volunteers
Authors: Duisters Kevin , Ogino Shinji , Andou Tomohiro , Ito Kazumi , Akabane Takafumi , Harms Amy , Moerland Matthijs , Hashimoto Yuka , Ando Ayumi , Ohtsu Yoshiaki , Wada Naoya , Yukinaga Hideo , Meulman Jacqueline , Kobayashi Hiroyuki , Kobayashi Nobuhiro , Suzumura Kenichi , Hankemeier Thomas
Published: August 2019

A limited understanding of intersubject and intrasubject variability hampers effective biomarker translation from in vitro/in vivo studies to clinical trials and clinical decision support. Specifically, variability of biomolecule concentration can play an important role in interpretation, power analysis, and sampling time designation. In the present study, a wide range of 749 plasma metabolites, 62 urine biogenic amines, and 1,263 plasma proteins were analyzed in 10 healthy male volunteers measured repeatedly during 12 hours under tightly controlled conditions. Three variability components in relative concentration data are determined using linear mixed models: between (intersubject), time (intrasubject), and noise (intrasubject). Biomolecules such as 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoate, platelet‐derived growth factor C, and cathepsin D with low noise potentially detect changing conditions within a person. If also the between component is low, biomolecules can easier differentiate conditions between persons, for example cathepsin D, CD27 antigen, and prolylglycine. Variability over time does not necessarily inhibit translatability, but requires choosing sampling times carefully.
Repeated cross‐fostering affects maternal behavior and olfactory preferences in rat pups
Authors: Dulor Finkler Andrea , Espinoza Pardo Grace Violeta , Bolten Lucion Aldo
Published: August 2019

Disturbances in early mother–infant relationships are strongly associated with changes in the development of a number of physiological and behavioral systems in the neonate that can create a complex change in patterns of vulnerability throughout life. Institutionalized children, despite receiving adequate care, display important behavioral changes in adult life, and such changes are strongly associated with a lack of selective and consistent attachment to the maternal figure in early life. It is not yet clear how human adoption processes alter the mother–infant relationship early in life. Here, to mimic the situation of human adoption and explore the impact on the formation of attachment between the infant and a caregiver, we use a repeated cross‐fostering (RCF) model in rodents in two postnatal periods, postnatal days (PND) 1 to 3 (early RCF) and 9 to 11 (late RCF). Early exposure but not late exposure to RCF reduces the pups' preference for the odor of the mother figure. Moreover, early exposure and slightly later exposure to RCF reduce maternal care and motivation in collecting the pups and bringing them to the nest. The RCF protocol creates an unstable environment for mother–pup interaction, but it seems to affect learned attachment to the mother only when it occurs during the corresponding sensitive period of development.
Inter‐rhombomeric interactions reveal roles for fibroblast growth factors signaling in segmental regulation of EphA4 expression
Authors: Cambronero Francisco , Ariza‐McNaughton Linda , Wiedemann Leanne M. , Krumlauf Robb
Published: August 2019

Background

The basic ground plan of vertebrate hindbrain is established through a process of segmentation, which generates eight transient lineage‐restricted cellular compartments called rhombomeres (r). The segments adopt distinct individual identities in response to axial patterning signals. It is unclear whether signaling between rhombomeres plays a conserved role in regulating segmental patterning during hindbrain development.

Results

Using tissue manipulations of rhombomeres in chicken embryos, we have uncovered roles for r2 and r4 in regulating the expression of EphA4 in r3 and r5. Perturbations of signaling pathways reveal that these regulatory inputs from r2 and r4 into EphA4 expression are mediated independent of inputs from Krox20 through cues involving fibroblast growth factor (FGF) signaling. These interactions are stage dependent and are set up in embryos with <10 somites.

Conclusions

We show that r2 and r4 function as temporally dynamic signaling centers in the early patterning of adjacent hindbrain segments and this activity is dependent upon the FGF pathway. These results reveal that inter‐rhombomeric signaling is a conserved feature of the regulatory networks that control the specification of individual rhombomere identities in vertebrate hindbrain segmentation. However, the timing of when restricted domains of FGF signaling are coupled to formation of r4 may vary between the species.
Effects of forest management on vertebrates: synthesizing two decades of data from hardwood forests in Missouri,USA
Authors: Kellner Kenneth F. , Renken Rochelle B. , Millspaugh Joshua J. , Porneluzi Paul A. , Wolf Alexander J. , Fantz Debby K. , Gitzen Robert A. , Faaborg John , Timm Shelby R. , Ehlers Shannon , Buchanan Megan L. , Haslerig Janet M. , George Andrew D. , Rota Christopher T.
Published: August 2019

Modern forest management seeks to balance multiple social, economic, and ecological goals. Different management approaches create different types of disturbances in a forest ecosystem and thus also differ in their impacts on plants, animals, and insects. Understanding these impacts is important for conservation of forest ecosystem function, but challenging due to the large spatial and temporal scale over which management occurs. Most past research has focused on relatively small areas, short time scales, and/or a small number of species. To address this, we examined the effects of two common silvicultural systems (even and uneven aged) on abundance and richness of three vertebrate taxa (birds, small mammals, and herpetofauna) over a two‐decade period in a temperate hardwood forest in Missouri,USA. The two systems removed a similar amount of biomass overall, but differed in the intensity, number, and configuration of harvests applied. We found that vertebrate population responses varied by taxa, occurred at multiple spatial scales, and were concentrated in the period following the first harvest entry. Birds generally had the largest changes in relative abundance, both positive and negative, following management. Small mammals and reptiles had smaller, but generally positive, responses; amphibians were mixed. Bird species tended to respond in the same way to both silvicultural systems, while small mammals and herpetofauna did not respond consistently. Thus, for birds, the total amount of harvest disturbance across the landscape drives population responses, while for others the size and configuration of individual harvests is likely more important. Synthesizing results across the vertebrate community at large spatial and temporal scales allows managers to better understand trade‐offs when making decisions that will affect wildlife in contrasting ways.
An effective method for ecosystem‐scale manipulation of bird abundance and species richness
Authors: Wood Chelsea L. , Summerside Margaret , Johnson Pieter T. J.
Published: August 2019

Manipulation experiments are a cornerstone of ecological research, but can be logistically challenging to execute—particularly when they are intended to isolate the ecological role of large, vagile species, like birds. Despite indirect evidence that birds are influential in many ecosystems, large‐scale, multi‐year bird manipulation experiments are rare. When these studies are conducted, they are typically realized with caged or netted exclosures, an approach that can be expensive, risky for wildlife, and difficult to maintain. In cases where caged exclosures are not appropriate, alternate approaches are needed to allow rigorous empirical studies on the ecological role of birds. Here, we present and validate a method for experimentally increasing the abundance and richness of birds at the scale of entire aquatic ecosystems. Unlike bird exclusion, this approach is experimentally tractable, appealing to land managers, and possible to deploy over large spatial scales. We tested the efficacy of our approach for increasing bird abundance and species richness at 16 central California ponds. Based on bird visitation data obtained by summer camera trapping, our approach significantly increased bird species richness and abundance at manipulated ponds compared to control ponds. Attractant treatments mitigated the negative effects of a major drought on bird species richness and generated a near doubling of bird abundance in the presence of attractants. Treatments had no effect on most mammal species, with the exception of ground squirrels, which increased in abundance in the presence of attractants. These results suggest that attractants are effective in increasing bird abundance and richness. We encourage researchers to consider this approach for experimentally isolating the ecological role of birds in aquatic and open terrestrial ecosystems, especially in cases where cost or logistical constraints preclude the use of caged or netted exclosures.
Emerging role of cardiac computed tomography in heart failure
Authors: Aziz Waqar , Claridge Simon , Ntalas Ioannis , Gould Justin , de Vecchi Adelaide , Razeghi Orod , Toth Daniel , Mountney Peter , Preston Rebecca , Rinaldi Christopher A. , Razavi Reza , Niederer Steven , Rajani Ronak
Published: August 2019

Despite medical advancements, the prognosis of patients with heart failure remains poor. While echocardiography and cardiac magnetic resonance imaging remain at the forefront of diagnosing and monitoring patients with heart failure, cardiac computed tomography (CT) has largely been considered to have a limited role. With the advancements in scanner design, technology, and computer processing power, cardiac CT is now emerging as a valuable adjunct to clinicians managing patients with heart failure. In the current manuscript, we review the current applications of cardiac CT to patients with heart failure and also the emerging areas of research where its clinical utility is likely to extend into the realm of treatment, procedural planning, and advanced heart failure therapy implementation.
Malnutrition in acute heart failure with preserved ejection fraction: clinical correlates and prognostic implications
Authors: Chien Shih‐Chieh , Lo Chi‐In , Lin Chao‐Feng , Sung Kuo‐Tzu , Tsai Jui‐Peng , Huang Wen‐Hung , Yun Chun‐Ho , Hung Ta‐Chuan , Lin Jiun‐Lu , Liu Chia‐Yuan , Hou Charles Jia‐Yin , Tsai I‐Hsien , Su Cheng‐Huang , Yeh Hung‐I , Hung Chung‐Lieh
Published: August 2019

Aims

This study aimed to evaluate the prognostic significance of nutritional status in post‐discharge Asians with heart failure with preserved ejection fraction (HFpEF).

Methods and results

We examined the prognostic implications of body mass index (BMI) and nutritional markers among consecutive patients hospitalized for HFpEF. Nutritional metrics were estimated by serum albumin (SA), prognostic nutritional index (PNI), Controlling Nutritional Status (CONUT) score, and geriatric nutritional risk index. Among 1120 patients (mean age: 77.2 ± 12.6 years, 39.4% men), mean SA levels, PNI, CONUT scores, and geriatric nutritional risk index were 3.3 ± 0.6 g/dL, 40.2 ± 8.7, 5.5 ± 2.1, and 95.9 ± 14.5, respectively. Lean body size, higher white blood cell counts and C‐reactive protein levels, anaemia, and lack of angiotensin blocker use were independently associated with malnutrition (defined by SA < 3.5 g/dL). Higher SA levels [hazard ratio (HR): 0.67 (95% confidence interval, CI: 0.53–0.85)], higher PNI [HR: 0.97 (95% CI: 0.95–0.99)], and higher geriatric nutritional risk index [HR: 0.98 (95% CI: 0.97–0.99)] (all P < 0.05) were all associated with longer survival, with higher CONUT score [HR: 1.08 (95% CI: 1.02–1.13)] exhibited higher mortality in Cox regression models and with higher SA levels/PNI but not BMI further contributing to the reduced rate of re‐hospitalization (both P < 0.05). Categorizing BMI (25 kg/m2 as cut‐off) and nutritional status showed significantly higher mortality rates among patients with lower BMI/malnutrition than among those with BMI/better nutrition (SA level, PNI, and CONUT score, all P < 0.01). Restricted cubic spline regression revealed a marked survival benefit of better nutrition with increasing BMI (adjusted Pinteraction for both SA level and PNI: <0.001; adjusted Pinteraction for CONUT score: 0.046).

Conclusions

Malnutrition was frequently and strongly associated with systemic inflammation in Asian patients hospitalized for acute HFpEF. Our findings also indicate that nutrition may play a pivotal role in metabolic protection in this population.
Simultaneous optimization of the acidified water extraction for total anthocyanin content, total phenolic content, and antioxidant activity of blue honeysuckle berries (Lonicera caerulea L.) using response surface methodology
Authors: Li Fengfeng , Zhao Hengtian , Xu Ruiru , Zhang Xiuling , Zhang Wentao , Du Meiling , Liu Xiaochen , Fan Lili
Published: August 2019

The purpose of this study was to optimize the total anthocyanin content (TAC), total phenolic content (TPC), and antioxidant activity of acidified water extract from blue honeysuckle berries by response surface methodology (RSM). The optimized conditions were HCl concentration of 0.35%, liquid–solid ratio of 49.42 ml/g, and extraction temperature of 41.56°C for total anthocyanin content (24.01 ± 0.37 mg/g), total phenolic content (207.03 ± 3.31 mg/g), DPPH radical scavenging activity (68.24 ± 1.13%), and ABTS radical scavenging activity (70.05 ± 0.84%). The experimental results are consistent with the predicted values. The results showed that acidified water extraction was an effective, simple, and green technique for the extraction of total anthocyanins, total phenol, and antioxidant activity from blue honeysuckle berries.
Deletion of the RNA regulator HuR in tumor‐associated microglia and macrophages stimulates anti‐tumor immunity and attenuates glioma growth
Authors: Wang Jiping , Leavenworth Jianmei W. , Hjelmeland Anita B. , Smith Reed , Patel Neha , Borg Ben , Si Ying , King Peter H.
Published: August 2019

Glioblastoma is a malignant brain tumor that portends a poor prognosis. Its resilience, in part, is related to a remarkable capacity for manipulating the microenvironment to promote its growth and survival. Microglia/macrophages are prime targets, being drawn into the tumor and stimulated to produce factors that support tumor growth and evasion from the immune system. Here we show that the RNA regulator, HuR, plays a key role in the tumor‐promoting response of microglia/macrophages. Knockout (KO) of HuR led to reduced tumor growth and proliferation associated with prolonged survival in a murine model of glioblastoma. Analysis of tumor composition by flow cytometry showed that tumor‐associated macrophages (TAMs) were decreased, more polarized toward an M1‐like phenotype, and had reduced PD‐L1 expression. There was an overall increase in infiltrating CD4+ cells, including Th1 and cytotoxic effector cells, and a concomitant reduction in tumor‐associated polymorphonuclear myeloid‐derived suppressor cells. Molecular and cellular analyses of HuR KO TAMs and cultured microglia showed changes in migration, chemoattraction, and chemokine/cytokine profiles that provide potential mechanisms for the altered tumor microenvironment and reduced tumor growth in HuR KO mice. In summary, HuR is a key modulator of pro‐glioma responses by microglia/macrophages through the molecular regulation of chemokines, cytokines, and other factors. Our findings underscore the relevance of HuR as a therapeutic target in glioblastoma.
Emotions amplify speaker–listener neural alignment
Authors: Smirnov Dmitry , Saarimäki Heini , Glerean Enrico , Hari Riitta , Sams Mikko , Nummenmaa Lauri
Published: August 2019

Individuals often align their emotional states during conversation. Here, we reveal how such emotional alignment is reflected in synchronization of brain activity across speakers and listeners. Two “speaker” subjects told emotional and neutral autobiographical stories while their hemodynamic brain activity was measured with functional magnetic resonance imaging (fMRI). The stories were recorded and played back to 16 “listener” subjects during fMRI. After scanning, both speakers and listeners rated the moment‐to‐moment valence and arousal of the stories. Time‐varying similarity of the blood‐oxygenation‐level‐dependent (BOLD) time series was quantified by intersubject phase synchronization (ISPS) between speaker–listener pairs. Telling and listening to the stories elicited similar emotions across speaker–listener pairs. Arousal was associated with increased speaker–listener neural synchronization in brain regions supporting attentional, auditory, somatosensory, and motor processing. Valence was associated with increased speaker–listener neural synchronization in brain regions involved in emotional processing, including amygdala, hippocampus, and temporal pole. Speaker–listener synchronization of subjective feelings of arousal was associated with increased neural synchronization in somatosensory and subcortical brain regions; synchronization of valence was associated with neural synchronization in parietal cortices and midline structures. We propose that emotion‐dependent speaker–listener neural synchronization is associated with emotional contagion, thereby implying that listeners reproduce some aspects of the speaker's emotional state at the neural level.
Response to Bittner et al.: Polyethylene glycol fusion associated with antioxidants: A new promise in the treatment of traumatic paralysis
Authors: Salomone Raquel
Published: August 2019

See article on page 3737–3739, in this issue
Steady incompressible magnetohydrodynamics Casson boundary layer flow past a permeable vertical and exponentially shrinking sheet: A stability analysis
Authors: Lund Liaquat Ali , Omar Zurni , Khan Ilyas
Published: August 2019

Steady incompressible magnetohydrodynamic mixed convection boundary layer flow of a Casson fluid on an exponentially vertical shrinking sheet using the non‐Newtonian heating equation is investigated in this paper. There are three main objectives of this study, namely, to develop a new mathematical model, to obtain multiple solutions, and to perform stability analysis. The governing partial differential equations have been changed into nonlinear ordinary differential equations. The resultant equations of boundary value problems are then converted into the equivalent initial value problems using the shooting method before they can be solved using Runge‐Kutta of order four. The numerical results are obtained and found to be in good agreement with the published literature. The results also indicate that the velocity boundary layer becomes thinner as the magnetic, slip, and Casson parameters increase. Dual solutions for temperature and velocity distributions are obtained. Furthermore, the results suggest that the presence of the force of buoyancy (opposing flow case) would cause the occurrence of dual solutions. However, based on the stability analysis, only the first solution is stable.
Helminth‐derived molecules inhibit colitis‐associated colon cancer development through NF‐κB and STAT3 regulation
Authors: Callejas Blanca E. , Mendoza‐Rodríguez Mónica G. , Villamar‐Cruz Olga , Reyes‐Martínez Sandy , Sánchez‐Barrera Cuauhtémoc Angel , Rodríguez‐Sosa Miriam , Delgado‐Buenrostro Norma L. , Martínez‐Saucedo Diana , Chirino Yolanda I. , León‐Cabrera Sonia A. , Pérez‐Plasencia Carlos , Vaca‐Paniagua Felipe , Arias‐Romero Luis E. , Terrazas Luis I.
Published: August 2019

Inflammation is currently considered a hallmark of cancer and plays a decisive role in different stages of tumorigenesis, including initiation, promotion, progression, metastasis and resistance to antitumor therapies. Colorectal cancer is a disease widely associated with local chronic inflammation. Additionally, extrinsic factors such as infection may beneficially or detrimentally alter cancer progression. Several reports have noted the ability of various parasitic infections to modulate cancer development, favoring tumor progression in many cases and inhibiting tumorigenesis in others. The aim of our study was to determine the effects of excreted/secreted products of the helminth Taenia crassiceps (TcES) as a treatment in a murine model of colitis‐associated colon cancer (CAC). Here, we found that after inducing CAC, treatment with TcES was able to reduce inflammatory cytokines such as IL‐1β, TNF‐α, IL‐33 and IL‐17 and significantly attenuate colon tumorigenesis. This effect was associated with the inhibition of signal transducer and activator of transcription 3 and nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) phosphorylation. Furthermore, we determined that TcES interfered with LPS‐induced NF‐κB p65 activation in human colonic epithelial cell lines in a Raf‐1 proto‐oncogene‐dependent manner. Moreover, in three‐dimensional cultures, TcES promoted reorganization of the actin cytoskeleton, altering cell morphology and forming colonospheres, features associated with a low grade of aggressiveness. Our study demonstrates a remarkable effect of helminth‐derived molecules on suppressing ongoing colorectal cancer by downregulating proinflammatory and protumorigenic signaling pathways.