bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptations in muscle oxidative capacity, fiber size, and oxygen supply capacity after repeated-sprint training in hypoxia combined with chronic hypoxic exposure
Authors: van der Zwaard S. , Brocherie F. , Kom B. L. G. , Millet G. P. , Deldicque L. , van der Laarse W. J. , Girard O. , Jaspers R. T.
Published: February 2018

In this study, we investigate adaptations in muscle oxidative capacity, fiber size and oxygen supply capacity in team-sport athletes after six repeated-sprint sessions in normobaric hypoxia or normoxia combined with 14 days of chronic normobaric hypoxic exposure. Lowland elite field hockey players resided at simulated altitude (≥14 h/day at 2,800–3,000 m) and performed regular training plus six repeated-sprint sessions in normobaric hypoxia (3,000 m; LHTLH; n = 6) or normoxia (0 m; LHTL; n = 6) or lived at sea level with regular training only (LLTL; n = 6). Muscle biopsies were obtained from the m. vastus lateralis before (pre), immediately after (post-1), and 3 wk after the intervention (post-2). Changes over time between groups were compared, including likelihood of the effect size (ES). Succinate dehydrogenase activity in LHTLH largely increased from pre to post-1 (~35%), likely more than LHTL and LLTL (ESs = large-very large), and remained elevated in LHTLH at post-2 (~12%) vs. LHTL (ESs = moderate-large). Fiber cross-sectional area remained fairly similar in LHTLH from pre to post-1 and post-2 but was increased at post-1 and post-2 in LHTL and LLTL (ES = moderate-large). A unique observation was that LHTLH and LHTL, but not LLTL, improved their combination of fiber size and oxidative capacity. Small-to-moderate differences in oxygen supply capacity (i.e., myoglobin and capillarization) were observed between groups. In conclusion, elite team-sport athletes substantially increased their skeletal muscle oxidative capacity, while maintaining fiber size, after only 14 days of chronic hypoxic residence combined with six repeated-sprint training sessions in hypoxia.

NEW & NOTEWORTHY Our novel findings show that elite team-sport athletes were able to substantially increase the skeletal muscle oxidative capacity in type I and II fibers (+37 and +32%, respectively), while maintaining fiber size after only 14 days of chronic hypoxic residence combined with six repeated-sprint sessions in hypoxia. This increase in oxidative capacity was superior to groups performing chronic hypoxic residence with repeated sprints in normoxia and residence at sea level with regular training only.
Food Integrity and Food Technology Concerns in Canada: Evidence from Two Public Surveys
Authors: Goddard Ellen , Muringai Violet , Boaitey Albert
Published: February 2018

Food integrity and food technologies both generate public concerns. There is little research to show the interactions between those concerns in particular samples, especially in Canada. In this paper, data from two national online samples are used to examine an aggregate of food integrity concerns, genetic modification in food, and food nanotechnology concerns in the Canadian public. A variety of trust, health, environmental, and science attitude variables are used to help explain the concerns that vary across the population. In addition, the food integrity concerns are tested as explanatory variables in the technology concern models to establish whether there is a strong or weak link between the two. Tobit and ordered probit regressions are used to model the variables for each of the survey samples. Results are examined to see if they are consistent across surveys and also consistent with an earlier study that was done in Australia. The results suggest that trust in people and trust in a variety of agents within the food system are beliefs that ameliorate concerns about food integrity and the two technologies. However, trust in advocacy organizations appears to be related to higher concerns in each case. Fundamentally and similar to the earlier Australian study, positive scientific attitudes are a major determinant of reduced concerns about food integrity and the two technologies.
Involvement of Cholinergic Dysfunction and Oxidative Damage in the Effects of Simulated Weightlessness on Learning and Memory in Rats
Authors: Zhang Yongliang , Wang Qiong , Chen Hailong , Liu Xinmin , Lv Ke , Wang Tingmei , Wang Yanli , Ji Guohua , Cao Hongqing , Kan Guanghan , Li Yinghui , Qu Lina
Published: February 2018

The present study aimed to determine how the learning and memory gradually change with the prolonged hindlimb unloading (HU) treatment in rats. Different HU durations (7 d, 14 d, 21 d, and 28 d) in Sprague-Dawley (SD) rats were implemented. Cognitive function was assessed using the Morris water maze (MWM) and the shuttle box test. Additionally, parameters about cholinergic activity and oxidative stress were tested. Results showed that longer-than-14 d HU led to the inferior performances in the behavioral tasks. Besides, acetylcholine esterase (AChE) activity, malondialdehyde (MDA) level in brain, reactive oxygen species (ROS), and 8-hydroxy-2-deoxyguanosine (8-OHdG) concentrations of HU rats were significantly increased. Furthermore, choline acetyltransferase (ChAT), superoxide dismutase (SOD), and catalase (CAT) activity in brain were notably attenuated. Most of these effects were more pronounced after longer exposure (21 d and 28 d) to HU, although some indicators had their own characteristics of change. These results indicate that cholinergic dysfunction and oxidative damage were involved in the learning and memory impairments induced by longer-than-14 d HU. Moreover, the negative effects of HU tend to be augmented as the HU duration becomes longer. The results may be helpful to present possible biochemical targets for countermeasures development regarding the memory deficits under extreme environmental conditions.
Clinical Outcomes of Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae Infections with Susceptibilities among Levofloxacin, Cefepime, and Carbapenems
Authors: Walker Kristy J. , Lee Young R. , Klar Amanda R.
Published: February 2018

Purpose. Highly resistant Gram-negative bacterial infections are associated with high mortality. Increasing resistance to standard therapy illustrates the need for alternatives when treating resistant organisms, especially extended-spectrum beta-lactamase- (ESBL-) producing Enterobacteriaceae. Methods. A retrospective chart review at a community hospital was performed. Patients who developed ESBL-producing infections were included. Patients less than eighteen years old, who were pregnant, or who were incarcerated were excluded. The primary outcome was hospital mortality. The secondary outcomes included intensive care unit (ICU) mortality, ICU length of stay, and hospital length of stay. Results. 113 patients with ESBL-producing infections met the criteria for review. Hospital mortality: carbapenem (16.6%), cefepime (0%), and levofloxacin (15.3%) (p=0.253). ICU mortality: carbapenem (4.5%), cefepime, (0%), and levofloxacin (3.7%) (p=0.616). Mean ICU and hospital length of stay: carbapenem (9.8 ± 16, 12.1 ± 1 days), cefepime (7.8 ± 6, 11.1 ± 10.5 days), and levofloxacin (5.4 ± 4.1, 11.1 ± 10.4 days) (p=0.805,0.685). No predictors were clearly found between the source of infection and mortality. Conclusion. Cefepime or levofloxacin can be a potential alternative agent for infections with ESBL-producing Enterobacteriaceae, and larger clinical trials investigating these outcomes are warranted.
Differentiation of Promonocytic U937 Cells to Monocytes Is Associated with Reduced Mitochondrial Transport of Ascorbic Acid
Authors: Scotti Maddalena , Fiorani Mara , Guidarelli Andrea , Cantoni Orazio
Published: February 2018

Growth of promonocytic U937 cells in the presence of DMSO promotes their differentiation to monocytes. After 4 days of culture in differentiating medium, these cells ceased to proliferate, displayed downregulated ryanodine receptor expression, and responded to specific stimuli with enhanced NADPH‐oxidase‐derived superoxide formation or cytosolic phospholipase A2‐dependent arachidonic acid release. We found that the 4‐day differentiation process is also associated with downregulated SVCT2 mRNA expression, in the absence of apparent changes in SVCT2 protein expression and transport rate of ascorbic acid (AA). Interestingly, under the same conditions, these cells accumulated lower amounts of the vitamin in their mitochondria, with an ensuing reduced response to external stimuli sensitive to the mitochondrial fraction of AA. Further analyses demonstrated an unexpected increase in mitochondrial SVCT2 protein expression, however, associated with reduced SVCT2‐dependent AA uptake in isolated mitochondria. A decrease in the transporter Vmax, with no change in affinity, was found to account for this response. Differentiation of promonocytic cells to monocytes is therefore characterized by decreased SVCT2 mRNA expression that, even prior to the onset of SVCT2 protein downregulation or apparent changes in plasma membrane transport activity, impacts on the mitochondrial accumulation of the vitamin through a decreased Vmax of the transporter.
Asymmetric Double Strange Attractors in a Simple Autonomous Jerk Circuit
Authors: Kom G. H. , Kengne J. , Mboupda Pone J. R. , Kenne G. , Tiedeu A. B.
Published: February 2018

The dynamics of a simple autonomous jerk circuit previously introduced by Sprott in 2011 are investigated. In this paper, the model is described by a three‐time continuous dimensional autonomous system with an exponential nonlinearity. Using standard nonlinear techniques such as time series, bifurcation diagrams, Lyapunov exponent plots, and Poincaré sections, the dynamics of the system are characterized with respect to its parameters. Period‐doubling bifurcations, periodic windows, and coexisting bifurcations are reported. As a major result of this work, it is found that the system experiences the unusual phenomenon of asymmetric bistability marked by the presence of two different attractors (e.g., screw‐like Shilnikov attractor with a spiralling‐like Feigenbaum attractor) for the same parameters setting, depending solely on the choice of initial states. Among few cases of lower dimensional systems capable of such type of behavior reported to date (e.g., Colpitts oscillator, Newton–Leipnik system, and hyperchaotic oscillator with gyrators), the jerk circuit/system considered in this work represents the simplest prototype. Results of theoretical analysis are perfectly reproduced by laboratory experimental measurements.
Surgery to Treat Symptomatic Mobile Cecum Syndrome Is Safe and Associated with Good Recovery Outcomes
Authors: Cesaretti Manuela , Trotta Manuela , Leale Irene , Minetti Giuseppe Antonio , Cittadini Giuseppe , Montecucco Fabrizio , Camerini Giovanni Bruno , Borgonovo Giacomo
Published: February 2018

The mobile cecum syndrome includes a spectrum of conditions. The cecal volvulus represents the acute form, with typical feature of a bowel obstruction that needs immediate operative treatment. On the other hand, a chronic form of mobile cecum syndrome which is the most common form reported a history of intermittent crampy abdominal pain, distension, and constipation. In this study, five patients came to our attention during the last ten years, presenting different symptoms due to a mobile cecum. All patients were investigated by several diagnostic techniques according to the specific clinical setting. All patients were found to have the cecum and ascending colon unattached to the posterior peritoneum. Surgery was the treatment of choice. In our experience, the best diagnostic technique was computed tomography scan, especially if performed in the Trendelenburg position. We also propose virtual colonoscopy as a good option for diagnosis (in patients with chronic syndrome) and follow-up after surgery. In conclusion, laparoscopic approach guaranteed a good result, with no symptoms of recurrence, in both acute and elective treatments. The diagnosis of mobile cecum needs a high index of suspicion and a targeted radiological investigation. Surgery, especially laparoscopic cecopexy and appendectomy, is the recommended treatment.
Effects of Qingshen Granules on the Oxidative Stress‐NF/kB Signal Pathway in Unilateral Ureteral Obstruction Rats
Authors: Jin Hua , Wang Yiping , Wang Dong , Zhang Lei
Published: February 2018

Background. The activation of NF‐kappa B (NF/kB) signaling pathway plays an important role in the process of epithelial‐mesenchymal transition (EMT) and renal interstitial fibrosis (RIF) in renal tubules. The process of oxidative stress reaction in kidney is via excessive reactive oxygen species (ROS) production to activate NF/kB signaling pathway. Qingshen Granule (QSG) is an effective Chinese formula utilized to treat chronic renal failure. Previous studies confirmed that QSG could inhibit RIF in unilateral ureteral obstruction (UUO) rats. In this study, we used UUO rats to investigate the effects of QSG on oxidative stress and the activation of NF/kB signaling. Seventy male Sprague‐Dawley (SD) rats were randomly divided into a sham group, UUO model group, Qingshen Granules (QSG) high‐dose, medium‐dose, and low‐dose groups, PDTC group, and candesartan group (10 rats in each group). Our study demonstrated that oxidative stress‐NF/kB signal pathway contributed to the formation of UUO renal interstitial fibrosis. QSG may protect against RIF by inhibiting the oxidative stress‐NF/kB signal pathway, reducing inflammation, and improving renal tubular EMT.
Distributed Intrusion Sensor Using DFB Laser with Optical Feedback and Saturable Absorber
Authors: Choi Kyoo Nam
Published: February 2018

Characteristics of a distributed intrusion sensor using a coherent DFB laser diode with an external optical feedback and saturable absorber were experimentally investigated. The stimulus at a location of 2 km using a PZT transducer placed the location of a simulated intruder in Φ-OTDR trace after averaging 32 times. Field trials demonstrated the detection of a vehicle and a pedestrian crossing above the sensing line and a loop in a burial depth of 50 cm. This distributed intrusion sensor using a coherent DFB laser diode as the light source had the advantages of a simple structure and intruder detection capability at the underground burial location.
Sitagliptin Accelerates Endothelial Regeneration after Vascular Injury Independent from GLP1 Receptor Signaling
Authors: Remm Friederike , Kränkel Nicolle , Lener Daniela , Drucker Daniel J. , Sopper Sieghart , Brenner Christoph
Published: February 2018

Introduction. DPP4 inhibitors (gliptins) are commonly used antidiabetic drugs for the treatment of type 2 diabetes. Gliptins also act in a glucose-independent manner and show vasoregenerative effects. We have shown that gliptins can remarkably accelerate vascular healing after vascular injury. However, the underlying mechanisms remain unclear. Here, we examined potential signaling pathways linking gliptins to enhanced endothelial regeneration. Methods and Results. We used wild-type and GLP1 receptor knockout (Glp1r−/−) mice to investigate the underlying mechanisms of gliptin-induced reendothelialization. The prototype DPP4 inhibitor sitagliptin accelerated endothelial healing in both animal models. Improved endothelial growth was associated with gliptin-mediated progenitor cell recruitment into the diseased vascular wall via the SDF1-CXCR4 axis independent of GLP1R-dependent signaling pathways. Furthermore, SDF1 showed direct proproliferative effects on endothelial cells. Excessive neointimal formation was not observed in gliptin- or placebo-treated Glp1r−/− mice. Conclusion. We identified the SDF1-CXCR4 axis as a crucial signaling pathway for endothelial regeneration after acute vascular injury. Furthermore, SDF1 can directly increase endothelial cell proliferation. Gliptin-mediated potentiation of endothelial regeneration was preserved in Glp1r−/− animals. Thus, gliptin-mediated endothelial regeneration proceeds through SDF-1/CXCR4 in a GLP1R-independent manner after acute vascular injury.
Hybrid Assistive Limb Intervention in a Patient with Late Neurological Deterioration after Thoracic Myelopathy Surgery due to Ossification of the Ligamentum Flavum
Authors: Taketomi Masakazu , Shimizu Yukiyo , Kadone Hideki , Kubota Shigeki , Abe Tetsuya , Marushima Aiki , Ueno Tomoyuki , Endo Ayumu , Kawamoto Hiroaki , Matsumura Akira , Sankai Yoshiyuki , Hada Yasushi , Yamazaki Masashi
Published: February 2018

Purpose. We evaluated improvements in gait after using the Hybrid Assistive Limb (HAL®) exoskeleton robot in a patient with late-onset neurological deterioration of lower extremity function after undergoing thoracic spine surgery for a myelopathy due to ossification of the ligamentum flavum. Case Presentation. A 70-year-old man participated in ten 20 min sessions of HAL intervention, twice weekly for five weeks. The effects of each HAL session were evaluated based on changes in performance on the 10 m walk test (10 MWT), lower limb kinematics quantified from motion capture, and the activation ratio of the gastrocnemius, measured before and after the intervention. Muscle activity was recorded using surface electromyography and synchronized to measured kinematics. The HAL intervention improved gait speed and step length, with an increase in the hip flexion angle during the swing phase and a decrease in the activation ratio of the gastrocnemius. The modified Ashworth scale improved from 1+ to 1 and International Standards for Neurological and Functional Classification of Spinal Cord Injury motor scores from 34 to 49. Conclusion. Intervention using the HAL exoskeleton robot may be an effective method to improve functional ambulation in patients with chronic spinal disorders.
Experimental Study on Bond‐Slip Behavior of Bamboo Bolt‐Modified Slurry Interface under Pull‐Out Load
Authors: Lu Wei , Zhao Dong , Mao Xiao-fei , Ai Yu
Published: February 2018

This paper presents an analysis of bamboo bolt‐modified slurry interfaces based on 26 in situ axial pull‐out tests intended to highlight the mechanical behavior of interface under a fracture mode. Three impact factors are analyzed: anchorage length, bolt diameter, and bolt hole diameter, using the same materials of bamboo and modified slurry. The result shows that the interface between the bamboo bolt and anchoring agent is the control interface of an anchorage system, and the local behavior of the interface involves four stages: elastic, soften, friction, and decoupling. Distribution law and change trend of slippage, stress, and strain of anchoring interface along with the axial direction of an anchor bolt were analyzed. The result shows that there is effective anchoring length limit in this kind of interface, and that the complete decoupling phenomenon should not be neglected. Through a comparative analysis of the existing bond‐slip model and interface bond‐slip curve, and considering the correspondence of the strain‐slip curve and trilinear bond‐slip model simultaneously, a modified trilinear bond‐slip model has been proposed. The friction section of this model is limited, and shearing stress in the complete decoupling section is zero.
Enhanced Heat Transfer Characteristics of Graphite Concrete and Its Application in Energy Piles
Authors: Li Qingwen , Chen Lu , Ma Haotian , Huang Chung-Ho
Published: February 2018

The latest research on energy piles demonstrates that most scholars are focusing their attention on optimization by designing more efficient heat exchanger coils, analyzing the heat pump matching parameters, and so on. However, after more than 20 years of development, these traditional methods for improving the heat transfer efficiency of energy piles have reached a bottleneck, and a new approach for the continued enhancement of this technology must be investigated. In this study, powdered graphite with high heat transfer characteristics was included in a concrete mix to create graphite concrete piles with enhanced heat transfer characteristics. The results from theoretical analysis, laboratory testing, and numerical simulation indicate that using graphite to improve the heat transfer efficiency of a concrete material is an effective method for enhancing the thermal efficiency of an energy pile system. The research results also show that the heat transfer coefficient of the concrete exhibits greater improvement when the graphite content is greater than 15% under the same environmental temperature. After studying the performance of the proposed graphite concrete energy pile under different environmental temperatures (10°C, 20°C, 30°C, and 40°C), the results indicate that the working efficiency of the energy pile is better in the summer than in the winter. Finally, parameters such as the cast‐in pipe configuration and pile spacing are optimized.
Negative Mood States Correlate with Laterobasal Amygdala in Collegiate Football Players
Authors: Cho Han Byul , Bueler Charles Elliott , DiMuzio Jennifer , Hicks-Little Charlie , McGlade Erin , Lyoo In Kyoon , Yurgelun-Todd Deborah
Published: February 2018

A number of studies have suggested that sports-related concussion (SRC) may place individuals at increased risk for depression and negative outcomes including suicide. However, the mechanisms underlying a potential relationship between brain integrity and mood remain unclear. The current study is aimed at examining the association between amygdala shape, mood state, and postconcussion symptoms in collegiate football players. Thirty members of 1 football team completed the Profile of Mood States (POMS), the postconcussion symptom scale (PCSS), and an MRI protocol during preseason camp. T1-weighted images were acquired and three-dimensional amygdala and probabilistic maps were created for shape analysis. Correlation analyses between POMS and PCSS and the relationship between POMS and amygdala shape were completed. In the amygdala, the left laterobasal subregion showed a positive relationship with the POMS total score and subscales scores. No significant relationship between PCSS and amygdala shape was found. Significant positive correlations were found between POMS subscales and PCSS. These results indicate that amygdala structure may be more closely associated with negative mood states than postconcussion symptoms. These findings suggest that premorbid individual differences in effect may provide critical insight into the relationship between negative mood and outcomes in collegiate football players with SRC.
Ti-24Nb-4Zr-8Sn Alloy Pedicle Screw Improves Internal Vertebral Fixation by Reducing Stress-Shielding Effects in a Porcine Model
Authors: Qu Yang , Zheng Shuang , Dong Rongpeng , Kang Mingyang , Zhou Haohan , Zhao Dezhi , Zhao Jianwu
Published: February 2018

To ensure the biomechanical properties of Ti-24Nb-4Zr-8Sn, stress-shielding effects were compared between Ti-24Nb-4Zr-8Sn and Ti-6Al-4V fixation by using a porcine model. Twelve thoracolumbar spines (T12–L5) of 12-month-old male pigs were randomly divided into two groups: Ti-24Nb-4Zr-8Sn (EG,n=6) and Ti-6Al-4V (RG,n=6) fixation. Pedicle screw was fixed at the outer edge of L4-5 vertebral holes. Fourteen measuring points were selected on the front of transverse process and middle and posterior of L4-5 vertebra. Electronic universal testing machine was used to measure the strain resistance of measuring points after forward and backward flexion loading of 150 N. Meanwhile, stress resistance was compared between both groups. The strain and stress resistance of measurement points 1, 2, 5, 6, 9, and 10–14 in Ti-24Nb-4Zr-8Sn fixation was lower than that of Ti-6Al-4V fixation after forward and backward flexion loading(P<0.05). The strain and stress resistance of measurement points 3, 4, 7, and 8 was higher in Ti-24Nb-4Zr-8Sn fixation than that of Ti-6Al-4V fixation(P<0.05). Stress-shielding effects of Ti-24Nb-4Zr-8Sn internal fixation were less than that of Ti-6Al-4V internal fixation. These results suggest that Ti-24Nb-4Zr-8Sn elastic fixation has more biomechanical goals than conventional Ti-6Al-4V internal fixation by reducing stress-shielding effects.
Antisecretory Factor–Mediated Inhibition of Cell Volume Dynamics Produces Antitumor Activity in Glioblastoma
Authors: Ilkhanizadeh Shirin , Sabelström Hanna , Miroshnikova Yekaterina A. , Frantz Aaron , Zhu Wen , Idilli Aurora , Lakins Jon N. , Schmidt Christin , Quigley David A. , Fenster Trenten , Yuan Edith , Trzeciak Jacqueline R. , Saxena Supna , Lindberg Olle R. , Mouw Janna K. , Burdick Jason A. , Magnitsky Sergey , Berger Mitchel S. , Phillips Joanna J. , Arosio Daniele , Sun Dandan , Weaver Valerie M. , Weiss William A. , Persson Anders I.
Published: February 2018

Interstitial fluid pressure (IFP) presents a barrier to drug uptake in solid tumors, including the aggressive primary brain tumor glioblastoma (GBM). It remains unclear how fluid dynamics impacts tumor progression and can be targeted therapeutically. To address this issue, a novel telemetry-based approach was developed to measure changes in IFP during progression of GBM xenografts. Antisecretory factor (AF) is an endogenous protein that displays antisecretory effects in animals and patients. Here, endogenous induction of AF protein or exogenous administration of AF peptide reduced IFP and increased drug uptake in GBM xenografts. AF inhibited cell volume regulation of GBM cells, an effect that was phenocopied in vitro by the sodium-potassium-chloride cotransporter 1 (SLC12A2/NKCC1) inhibitor bumetanide. As a result, AF induced apoptosis and increased survival in GBM models. In vitro, the ability of AF to reduce GBM cell proliferation was phenocopied by bumetanide and NKCC1 knockdown. Next, AF's ability to sensitize GBM cells to the alkylating agent temozolomide, standard of care in GBM patients, was evaluated. Importantly, combination of AF induction and temozolomide treatment blocked regrowth in GBM xenografts. Thus, AF-mediated inhibition of cell volume regulation represents a novel strategy to increase drug uptake and improve outcome in GBM. Mol Cancer Res; 16(5); 777–90. ©2018 AACR.
BET Proteins Exhibit Transcriptional and Functional Opposition in the Epithelial-to-Mesenchymal Transition
Authors: Andrieu Guillaume P. , Denis Gerald V.
Published: February 2018

Transcriptional programs in embryogenesis and cancer, such as the epithelial-to-mesenchymal transition (EMT), ensure cellular plasticity, an essential feature of carcinoma progression. As effectors of signal transduction, the bromodomain and extraterminal (BET) proteins are well suited to support plasticity because they function as co-activators or co-repressors of mammalian transcriptomes. Here, using both hormone-sensitive and triple-negative breast cancer (TNBC) model systems, we systematically altered EMT transcriptional profiles by manipulating individual BET proteins and found that BRD2 positively regulates EMT, whereas BRD3 and BRD4 repress this program. Knockdown of individual BET proteins revealed independent transcriptional networks that differed from each other and from the small-molecule pan-BET inhibitor JQ1, which previously had been misleadingly asserted to be BRD4-selective. Available small-molecule pan-BET inhibitors, proposed as antiproliferative agents in cancer clinical trials, obscure these biological differences. Transcriptional profiling reveals that individual BET proteins, inhibited separately, engage in and control EMT through unique processes.

Implications: The distinct and opposing functions of BET proteins in the EMT process suggests the need for more member-selective epigenetic targeting agents.

Visual Overview: http://mcr.aacrjournals.org/content/molcanres/16/4/580/F1.large.jpg. Mol Cancer Res; 16(4); 580–6. ©2018 AACR.
Convergent Therapeutic Strategies to Overcome the Heterogeneity of Acquired Resistance in BRAFV600E Colorectal Cancer
Authors: Hazar-Rethinam Mehlika , Kleyman Marianna , Han G. Celine , Liu David , Ahronian Leanne G. , Shahzade Heather A. , Chen Lifeng , Parikh Aparna R. , Allen Jill N. , Clark Jeffrey W. , Kwak Eunice L. , Faris Jason E. , Murphy Janet E. , Hong Theodore S. , Van Seventer Emily E. , Nadres Brandon , Hong Catriona B. , Gurski Joseph M. , Jessop Nicholas A. , Dias-Santagata Dora , Iafrate A. John , Van Allen Eliezer M. , Corcoran Ryan B.
Published: February 2018

Clonal heterogeneity associated with acquired resistance presents a critical therapeutic challenge. Whole-exome sequencing of paired tumor biopsies and targeted sequencing of cell-free DNA (cfDNA) from patients with BRAFV600E colorectal cancer receiving BRAF inhibitor combinations identified 14 distinct alterations in MAPK pathway components driving acquired resistance, with as many as eight alterations in a single patient. We developed a pooled clone system to study clonal outgrowth during acquired resistance, in vitro and in vivo. In vitro, the dynamics of individual resistant clones could be monitored in real time in cfDNA isolated from culture media during therapy. Outgrowth of multiple resistant clones was observed during therapy with BRAF, EGFR, and MEK inhibitor combinations. However, ERK inhibition, particularly in combination with BRAF and EGFR inhibition, markedly abrogated clonal outgrowth in vitro and in vivo. Thus, convergent, up-front therapy may suppress outgrowth of heterogeneous clones harboring clinically observed resistance alterations, which may improve clinical outcome.

Significance: We observed heterogeneous, recurrent alterations in the MAPK pathway as key drivers of acquired resistance in BRAFV600E colorectal cancer, with multiple concurrent resistance alterations detectable in individual patients. Using a novel pooled clone system, we identify convergent up-front therapeutic strategies capable of intercepting multiple resistance mechanisms as potential approaches to suppress emergence of acquired resistance. Cancer Discov; 8(4); 417–27. ©2018 AACR.

See related commentary by Janku, p. 389.

See related article by Corcoran et al., p. 428.

This article is highlighted in the In This Issue feature, p. 371
A Critical Need for Better Cancer Immunotherapy Models: Are Organotypic Tumor Spheroid Cultures the Answer?
Authors: Balko Justin M. , Sosman Jeffrey A.
Published: February 2018

Summary: Immunotherapy has transformed the therapeutic landscape of cancer, but the preclinical evaluation of combination approaches that will deepen and broaden its clinical benefit has lagged far behind due to the lack of expedient and easily accessible ex vivo human systems. In this issue, Jenkins and colleagues and Deng and colleagues report the use of organotypic cultures of tumors derived from mice and humans containing both tumor cells and cells from their local immune microenvironment to recapitulate the in vivo use of immune checkpoint inhibitors and extend the application of this system to therapeutic combinations of immune checkpoint blockade and molecularly targeted agents. Cancer Discov; 8(2); 143–5. ©2018 AACR.

See related article by Jenkins et al., p. 196.

See related article by Deng et al., p. 216.
Association between Toll-Like Receptor 4 T399I Gene Polymorphism and the Susceptibility to Crohn’s Disease: A Meta-Analysis of Case-Control Studies
Authors: Fu Zhiquan , Shen Yanting , Lin Liubing , Chen Yirong , Li Yong , Que Renye
Published: February 2018

Background/Aims: This article was undertaken to investigate the association of toll-like receptor 4 (TLR4) polymorphism (Thr399Ile) and risk of Crohn’s disease (CD) by performing a meta-analysis. Methods: Articles were chosen based on PubMed, Embase, China National Knowledge Internet, and Chinese Wanfang databases (up to 12th October 2016). Specific inclusion criteria were used to evaluate articles. Meta-analysis was performed by using a random or fixed effect model. Fifteen eligible case-control studies were finally included into this meta-analysis. We estimated the summary OR with its corresponding 95% CI to assess the association. Results: Summary results of this meta-analysis showed a moderate association between the TLR4 T399I polymorphism and the risk of CD (allele model: OR 1.26, 95% CI 1.06–1.50, p = 0.009; heterozygote model: OR 1.36, 95% CI 1.11–1.66, p = 0.003; dominant model: OR 1.35, 95% CI 1.10–1.64, p = 0.004; homozygote model: OR 1.08, 95% CI 0.44–2.64, p = 0.866; recessive model: OR 0.97, 95% CI 0.40–2.35, p = 0.946). Stratified analysis on geographical area, ethnicity, and genotypic methods suggested that the polymorphism was associated with increased risk of CD in Asia and Asians, and “T” allele only moderately increased CD risk within polymerase chain reaction-restricted fragment length polymorphism. Conclusions: Our meta-analysis suggests that TLR4 T399I polymorphism is moderately associated with susceptibility to CD, and more studies are needed to confirm our conclusion.
Validation of a Piezoelectric Sensor Array-Based Device for Measurement of Carotid-Femoral Pulse Wave Velocity: The Philips Prototype
Authors: Xu Shao-Kun , Hong Xiang-Fei , Cheng Yi-Bang , Liu Chang-Yuan , Li Yan , Yin Bin , Wang Ji-Guang
Published: February 2018

Background: Multiple piezoelectric pressure mechanotransducers topologized into an array might improve efficiency and accuracy in collecting arterial pressure waveforms for measurement of pulse wave velocity (PWV). Objective: In the present study, we validated a piezoelectric sensor array-based prototype (Philips) against the validated and clinically widely used Complior device (Alam Medical). Methods: We recruited 33 subjects with a wide distribution of PWV. For the validation, PWV was measured sequentially with the Complior device (four times) and the Philips prototype (three times). With the 99 paired PWV values, we investigated the agreement between the Philips prototype and the Complior device using Pearson correlation analysis and Bland-Altman plot. We also performed analysis on the determinants and reproducibility of PWV measured with both devices. Results: The correlation coefficient for PWV measured with the two devices was 0.92 (p < 0.0001). Compared with the Complior device, the Philips prototype slightly overestimated PWV by 0.24 (± 2 standard deviations, ± 1.91) m/s, especially when PWV was high. The correlation coefficient between the difference and the average of the Philips and Complior measurements was 0.21 (p = 0.035). Nonetheless, they had similar determinants. Age, mean arterial pressure, and sex altogether explained 81.6 and 83.9% of the variance of PWV values measured with the Philips prototype and Complior device, respectively. When the two extremes of the three PWV values measured with the Philips prototype and the Complior device were investigated, the coefficients of variation were 8.26 and 3.26%, respectively. Conclusions: Compared with the Complior device, the Philips prototype had similar accuracy, determinants, and reproducibility in measuring PWV.
Serum Soluble Interleukin 2 Receptor Level as a Marker of Acute Rejection in Pediatric Kidney Transplant Recipients
Authors: Hagras Amal M. , Salah Doaa M. , Ahmed Dina H. , Abd Elaal Omnia K. , Elghobary Hany Ahmed Fouad , Fadel Fatina I.
Published: February 2018

Background: Despite advances in immunosuppression, acute allograft rejection remains one of the key factors affecting patient and graft survival in pediatric kidney transplantation. The aim of the study is to evaluate the role of serum soluble IL2 receptor (sIL2R) level as a noninvasive assessment parameter of acute rejection (AR). Method: Serum sIL2R level was measured (using enzyme-linked immune-sorbent assay technique) in 60 pediatric kidney transplant recipients (30 recipients with AR and 30 transplant recipients with stable graft function). Results: The mean values of sIL2R level in patients experiencing AR (14.8 ± 6.54) ng/mL were significantly higher than that in patients with stable graft functions (6.44 ±1.95) ng/mL (p = 0.0001). In addition; patients with AR proved by graft biopsy had their mean values of sIL2R level (16.19 ± 7.48) ng/mL significantly higher than that of other recipients in the study population (p = 0.032). Conclusion: Serum sIL2R level may serve as a noninvasive diagnostic indicator in pediatric kidney transplant recipients experiencing AR.
Increased Gastric Retention Capacity, Assessed by Scintigraphy, after APC Treatment of Dilated Gastrojejunal Anastomosis
Authors: Barrichello Sérgio , Galvão Neto Manoel dos Passos , Ferreira de Souza Thiago , Guimarães Hourmeaux de Moura Eduardo , Minata Maurício , Oliveira de Quadros Ana Paula , Waisberg Jaques , Grecco Eduardo , Macedo Guilherme , Silva Marco , de Quadros Luiz Gustavo
Published: February 2018

Background: Weight regain occurs in about 20% of patients after Roux-en-Y gastric bypass (RYGB). Studies have reported that in most cases this regain is associated with dilatation of the gastrojejunal anastomosis. To correct this dilatation, one of the methods used is the application of argon plasma coagulation (APC). Case: The authors report the case of a 39-year-old woman submitted to RYGB who had weight regain. In the endoscopic evaluation, the patient presented with dilatation of the gastrojejunal anastomosis, for which treatment with APC and an adjusted diet was proposed. After 3 sessions of APC, the patient presented with a reduction of the anastomosis diameter, weight loss, and increased satiety to food, with an increased gastric emptying time evidenced by scintigraphy. Conclusion: APC proved to be a safe and efficacious method.
Does a Ureteral Obstruction Affect the Contralateral Kidney Morphology? A Stereological Analysis in a Rodent Model
Authors: Assumção Rômulo F. , Pereira-Sampaio Marco A. , Sampaio Francisco J.B. , de Souza Diogo B.
Published: February 2018

Objective: To investigate, in a rodent model, the influence of an obstructed kidney/ureter on the contralateral organ morphology. Methods: Thirty-six rats were randomly assigned into the following groups: untreated ureteral obstruction group (UO-U, n = 10), submitted to a ligature of the ureter at day 0; UO group (at day 0) followed by nephrectomy after 24 h (UO-N, n = 8); nephrectomy group (N, n = 9), submitted to nephrectomy at day 0; and sham group (S, n = 9), submitted to simulated surgery at day 0. All these procedures were performed on the left kidney/ureter. All animals were euthanized 30 days after surgery, and the right kidneys were collected for stereological analysis. Data were compared using a one-way analysis of variance with Bonferroni’s post test, considering p < 0.05 as significant. Results: The kidney volume, weight, and cortical volume were augmented in groups UO-N and N, compared to group S. Kidneys from the UO-U group showed only a moderate augmentation in kidney weight, with a reduction in the cortical-medullar ratio, compared to the kidneys in group S. No differences in the glomerular volumetric density, volume-weighted glomerular volume, and number of glomeruli were observed among the right kidneys of the studied groups. Conclusion: An obstructed kidney/ureter is more prejudicial to the contralateral kidney morphology than an absent kidney.
C3 Glomerulopathy and Atypical Hemolytic Uremic Syndrome: Two Important Manifestations of Complement System Dysfunction
Authors: Bajwa Ravneet , DePalma John A. , Khan Taimoor , Cheema Anmol , Kalathil Sheila A. , Hossain Mohammad A. , Haroon Attiya , Madhurima Anne , Zheng Min , Nayer Ali , Asif Arif
Published: February 2018

The advances in our understanding of the alternative pathway have emphasized that uncontrolled hyperactivity of this pathway causes 2 distinct disorders that adversely impact the kidney. In the so-called atypical hemolytic uremic syndrome (aHUS), renal dysfunction occurs along with thrombocytopenia, anemia, and target organ injury to multiple organs, most commonly the kidney. On the other hand, in the so-termed C3 glomerulopathy, kidney involvement is not associated with thrombocytopenia, anemia, or other system involvement. In this report, we present 2 cases of alternative pathway dysfunction. The 60-year-old female patient had biopsy-proven C3 glomerulopathy, while the 32-year-old female patient was diagnosed with aHUS based on renal dysfunction, thrombocytopenia, anemia, and normal ADAMTS-13 level. The aHUS patient was successfully treated with the monoclonal antibody (eculizumab) for complement blockade. The patient with C3 glomerulopathy did not receive the monoclonal antibody. In this patient, management focused on blood pressure and proteinuria control with an angiotensin-converting enzyme inhibitor. This article focuses on the clinical differences, pathophysiology, and treatment of aHUS and C3 glomerulopathy.
Ocular Injury due to Potassium Permanganate Granules
Authors: Chirapapaisan Chareenun , Prabhasawat Pinnita , Srivannaboon Sabong , Roongpoovapatr Vatookarn , Chitsuthipakorn Piyada
Published: February 2018

Purpose: We report a rare case of ocular injury due to potassium permanganate (KMnO4) granules in a child. Methods: This is a retrospective case report. Results: A 2-year-old boy was transferred to our emergency room with severe pain in his right eye, inflamed eyelids, and brownish stains on his fingers. Chemical injury was suspected. Copious eye irrigation was immediately performed. Diffuse brownish splotches were then observed at the inferior bulbar conjunctiva. Otherwise, systemic organs were intact. Complete eye exam under general anesthesia revealed a 5-mm epithelial defect at the central cornea, along with generalized conjunctival injection and limbal ischemia, inferiorly. Multiple semi-dissolved granules of KMnO4 trapped in the inferior fornix were identified. The chemical particles were gradually washed out and removed; however, the brownish stains remained. The patient received preservative-free steroid, antibiotic eye drops, and lubricants as regular management for mild to moderate degree of ocular burn. Pseudomembrane developed early and transformed into symblepharon within a few days after the injury. Membrane adhesion was lysed, and more aggressive medications were then substituted. Commercial amniotic membrane (PROKERA®) was also applied to promote wound healing and to prevent recurrence of symblepharon. The ocular surface was eventually restored, and corneal transparency was preserved. Conclusion: Ocular injury with the granular form of KMnO4 is rare. Its toxicity is comparable to concentrated KMnO4 solution. However, the dissolved particles that had been absorbed in the stained conjunctiva were continuously released and damaged the ocular surface more than we primarily anticipated. Awareness of this condition and prompt management yield a good treatment outcome.
ФОРМУВАННЯ КОМПЕТЕНТНОСТІ МЕДИЧНИХ СЕСТЕР
Authors: Lуtvуnovа A. E.
Published: February 2018

У зв’язку з швидким темпом розвитку медичної галузі постає питання відповідності рівня компетентності медичних працівників. Тому оптимізація методів навчання фахівців на основі компетентнісного підходу займає значне місце у системі викладання. Зокрема, студенти освоюють дисципліну «Сестринська етика та деонтологія», яка включає теми професійної поведінки медсестри, взаємозв’язок медичного персоналу, етичні та деонтологічні проблеми сучасної медичної науки, сучасні проблеми медичної етики та деонтології.
УПРОВАДЖЕННЯ АЛГОРИТМІЗАЦІЇ В МЕДСЕСТРИНСЬКУ ОСВІТУ
Authors: Popovych N. V.
Published: February 2018

У статті проаналізовано поняття «алгоритм» і «алгоритмізація навчання», доцільність застосування даної педагогічної технології  при підготовці медичної сестри.
СІМЕЙНИЙ КОНФЛІКТ: ПРИЧИНИ ВИНИКНЕННЯ, ПОПЕРЕДЖЕННЯ, ВРЕГУЛЮВАННЯ
Authors: Krugla T. O.
Published: February 2018

У статті висвітлено причини виникнення сімейних конфліктів. Узагальнена інформація щодо попередження та врегулювання конфліктів у сім’ї. Проаналізовано стан теоретичної розробки досліджуваної проблеми.
ДО ПИТАННЯ ПРО ІННОВАЦІЙНІ МЕТОДИ ОБЛІКУ В РОБОТІ МЕДСЕСТЕР за УМОВ РЕФОРМУВАННЯ ГАЛУЗІ
Authors: Harasymiv O. I.
Published: February 2018

У статті йдеться про електронний метод обліку як інновацію в роботі медсестер за умов реформування галузі охорони здоровʼя. Обґрунтовано підвищення результативності діяльності закладу охорони здоровʼя за умов таких інноваційних впроваджень.
Sperm-binding to the perivitelline membrane of chicken egg yolk as a functional test for sperm evaluation in dogs
Authors: Brito Maíra Morales , Losano João Diego Agostini , Angrimani Daniel De Souza Ramos , Lúcio Cristina De Fátima , Dalmazzo Andressa , Nichi Marcílio , Vannucchi Camila Infantosi
Published: February 2018

Durante a fecundação, os espermatozoides interagem com a zona pelúcida (ZP) por meio da ligação entre o acrossomo e as proteínas 2 e 3 (ZP2 e ZP3). A membrana perivitelínica da gema de ovo de galinhas é homóloga à ZP3 de mamíferos, possibilitando a ligação espermática de diversas espécies. Este trabalho padronizou e avaliou a eficiência do teste de ligação espermática à membrana perivitelínica da gema de ovo de galinhas como avaliação funcional do sêmen de cães. Para tal, foram utilizadas nove amostras seminais previamente criopreservadas. Cada amostra foi dividida em duas alíquotas: a primeira foi mantida em banho-maria à 37ºC (vivos) e a segunda submetida a choque térmico com o intuito de induzir dano celular (mortos). As duas alíquotas foram misturadas, correspondendo a 0, 25, 50, 75 e 100% de células viáveis. As amostras foram avaliadas quanto ao número de espermatozoides ligados à membrana perivitelínica por meio da análise computadorizada da motilidade (CASA) ou microscopia convencional. Ademais, as amostras foram avaliadas quanto à motilidade espermática, integridade das membranas acrossomal e plasmática e atividade mitocondrial espermática. O teste de ligação espermática à membrana perivitelínica de ovos de galinha foi considerado um teste de análise seminal exequível tanto para avaliar a capacidade fecundante dos espermatozoides como atributos seminais gerais, especialmente quando realizado em microscopia convencional, expandindo sua praticidade para a maioria dos laboratórios de análise de sêmen canino.
Saturated Fatty Acids Undergo Intracellular Crystallization and Activate the NLRP3 Inflammasome in Macrophages
Authors: Karasawa Tadayoshi , Kawashima Akira , Usui-Kawanishi Fumitake , Watanabe Sachiko , Kimura Hiroaki , Kamata Ryo , Shirasuna Koumei , Koyama Yutaro , Sato-Tomita Ayana , Matsuzaka Takashi , Tomoda Hiroshi , Park Sam-Yong , Shibayama Naoya , Shimano Hitoshi , Kasahara Tadashi , Takahashi Masafumi
Published: February 2018

Objective—

Inflammation provoked by the imbalance of fatty acid composition, such as excess saturated fatty acids (SFAs), is implicated in the development of metabolic diseases. Recent investigations suggest the possible role of the NLRP3 (nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3) inflammasome, which regulates IL-1β (interleukin 1β) release and leads to inflammation, in this process. Therefore, we investigated the underlying mechanism by which SFAs trigger NLRP3 inflammasome activation.

Approach and Results—

The treatment with SFAs, such as palmitic acid and stearic acid, promoted IL-1β release in murine primary macrophages while treatment with oleic acid inhibited SFA-induced IL-1β release in a dose-dependent manner. Analyses using polarized light microscopy revealed that intracellular crystallization was provoked in SFA-treated macrophages. As well as IL-1β release, the intracellular crystallization and lysosomal dysfunction were inhibited in the presence of oleic acid. These results suggest that SFAs activate NLRP3 inflammasome through intracellular crystallization. Indeed, SFA-derived crystals activated NLRP3 inflammasome and subsequent IL-1β release via lysosomal dysfunction. Excess SFAs also induced crystallization and IL-1β release in vivo. Furthermore, SFA-derived crystals provoked acute inflammation, which was impaired in IL-1β–deficient mice.

Conclusions—

These findings demonstrate that excess SFAs cause intracellular crystallization and subsequent lysosomal dysfunction, leading to the activation of the NLRP3 inflammasome, and provide novel insights into the pathogenesis of metabolic diseases.