bluuebunny/crossref_metadata_2025 huggingface dataset:
Organic anion transporter OAT3 enhances the glucosuric effect of the SGLT2 inhibitor empagliflozin
Authors: Fu Yiling , Breljak Davorka , Onishi Akira , Batz Falk , Patel Rohit , Huang Winnie , Song Panai , Freeman Brent , Mayoux Eric , Koepsell Hermann , Anzai Naohiko , Nigam Sanjay K. , Sabolic Ivan , Vallon Volker
Published: February 2018

The sodium-glucose cotransporter SGLT2 inhibitor empagliflozin (plasma protein binding ~88%) may reach its target in the brush border of the early proximal tubule by glomerular filtration and tubular secretion. Here we determined whether empagliflozin is secreted by renal tubules in mice and whether genetic knockout of the basolateral organic anion transporter 3 ( Oat3−/−) affects its tubular secretion or glucosuric effect. Renal clearance studies in wild-type (WT) mice showed that tubular secretion accounted for 50–70% of empagliflozin urinary excretion. Immunostaining indicated that SGLT2 and OAT3 localization partially overlapped in proximal tubule S1 and S2 segments. Glucosuria in metabolic cage studies was reduced in Oat3−/− vs. WT mice for acute empagliflozin doses of 1, 3, and 10 mg/kg, whereas 30 mg/kg induced similar maximal glucosuria in both genotypes. Chronic application of empagliflozin (~25 mg·kg−1 ·day−1) in Oat3−/− mice was associated with lower urinary glucose-to-creatinine ratios despite maintaining slightly higher blood glucose levels than WT. On a whole kidney level, renal secretion of empagliflozin was largely unchanged in Oat3−/− mice. However, the absence of OAT3 attenuated the influence of empagliflozin on fractional glucose excretion; higher levels of plasma or filtered empagliflozin were needed to induce similar increases in fractional renal glucose excretion. We conclude that empagliflozin is excreted into the urine to similar extent by glomerular filtration and tubular secretion. The latter can occur largely independent of OAT3. However, OAT3 increases the glucosuric effect of empagliflozin, which may relate to the partial overlap of its localization with SGLT2 and thus OAT3-mediated tubular secretion of empagliflozin in the early proximal tubule.
Spatial persistence of reduced specific ventilation following methacholine challenge in the healthy human lung
Authors: Geier E. T. , Neuhart I. , Theilmann R. J. , Prisk G. K. , Sá R. C.
Published: February 2018

Specific ventilation imaging was used to identify regions of the healthy lung (6 supine subjects, ages 21–41 yr, 3 men) that experienced a fall in specific ventilation following inhalation of methacholine. This test was repeated 1 wk later and 3 mo later to test for spatial recurrence. Our data showed that 53% confidence interval (CI; 46%, 59%) of volume elements that constricted during one methacholine challenge did so again in another and that this quantity did not vary with time; 46% CI (28%, 64%) recurred 1 wk later, and 56% CI (51%, 61%) recurred 3 mo later. Previous constriction was a strong predictor for future constriction. Volume elements that constricted during one challenge were 7.7 CI (5.2, 10.2) times more likely than nonconstricted elements to constrict in a second challenge, regardless of whether the second episode was 1 wk [7.7 CI (2.9, 12.4)] or 3 mo [7.7 CI (4.6, 10.8)] later. Furthermore, posterior lung elements were more likely to constrict following methacholine than anterior lung elements (volume fraction 0.43 ± 0.22 posterior vs. 0.10 ± 0.03 anterior; P = 0.005), and basal elements that constricted were more likely than their apical counterparts to do so persistently through all three trials (volume fraction 0.14 ± 0.04 basal vs. 0.04 ± 0.04 apical; P = 0.003). Taken together, this evidence suggests a physiological predisposition toward constriction in some lung elements, especially those located in the posterior and basal lung when the subject is supine.

NEW & NOTEWORTHY The spatial pattern of bronchoconstriction following methacholine is persistent over time in healthy individuals, in whom chronic inflammation and airway remodeling are assumed to be absent. This suggests that regional lung inflation and airway structure may play dominant roles in determining the spatial pattern of methacholine bronchoconstriction.
Ischemic conditioning increases strength and volitional activation of paretic muscle in chronic stroke: a pilot study
Authors: Hyngstrom Allison S. , Murphy Spencer A. , Nguyen Jennifer , Schmit Brian D. , Negro Francesco , Gutterman David D. , Durand Matthew J.
Published: February 2018

Ischemic conditioning (IC) on the arm or leg has emerged as an intervention to improve strength and performance in healthy populations, but the effects on neurological populations are unknown. The purpose of this study was to quantify the effects of a single session of IC on knee extensor strength and muscle activation in chronic stroke survivors. Maximal knee extensor torque measurements and surface EMG were quantified in 10 chronic stroke survivors (>1 yr poststroke) with hemiparesis before and after a single session of IC or sham on the paretic leg. IC consisted of 5 min of compression with a proximal thigh cuff (inflation pressure = 225 mmHg for IC or 25 mmHg for sham) followed by 5 min of rest. This was repeated five times. Maximal knee extensor strength, EMG magnitude, and motor unit firing behavior were measured before and immediately after IC or sham. IC increased paretic leg strength by 10.6 ± 8.5 Nm, whereas no difference was observed in the sham group (change in sham = 1.3 ± 2.9 Nm, P = 0.001 IC vs. sham). IC-induced increases in strength were accompanied by a 31 ± 15% increase in the magnitude of muscle EMG during maximal contractions and a 5% decrease in motor unit recruitment thresholds during submaximal contractions. Individuals who had the most asymmetry in strength between their paretic and nonparetic legs had the largest increases in strength ( r2 = 0.54). This study provides evidence that a single session of IC can increase strength through improved muscle activation in chronic stroke survivors.

NEW & NOTEWORTHY Present rehabilitation strategies for chronic stroke survivors do not optimally activate paretic muscle, and this limits potential strength gains. Ischemic conditioning of a limb has emerged as an effective strategy to improve muscle performance in healthy individuals but has never been tested in neurological populations. In this study, we show that ischemic conditioning on the paretic leg of chronic stroke survivors can increase leg strength and muscle activation while reducing motor unit recruitment thresholds.
Circadian Etiology of Type 2 Diabetes Mellitus
Authors: Javeed Naureen , Matveyenko Aleksey V.
Published: February 2018

The epidemic of Type 2 diabetes mellitus necessitates development of novel therapeutic and preventative strategies to attenuate expansion of this debilitating disease. Evidence links the circadian system to various aspects of diabetes pathophysiology and treatment. The aim of this review will be to outline the rationale for therapeutic targeting of the circadian system in the treatment and prevention of Type 2 diabetes mellitus and consequent metabolic comorbidities.
Mitophagy in Cardiomyocytes and in Platelets: A Major Mechanism of Cardioprotection Against Ischemia/Reperfusion Injury
Authors: Zhang Weilin , Chen Chuyan , Wang Jun , Liu Lei , He Yubin , Chen Quan
Published: February 2018

Mitophagy, a process that selectively removes damaged organelles by autolysosomal degradation, is an early cellular response to ischemia. Mitophagy is activated in both cardiomyocytes and platelets during ischemia/reperfusion (I/R) and heart disease conditions. We focus on the molecular regulation of mitophagy and highlight the role of mitophagy in cardioprotection.
Role of Astrocytic Mitochondria in Limiting Ischemic Brain Injury?
Authors: Shih Evelyn K. , Robinson Michael B.
Published: February 2018

Until recently, astrocyte processes were thought to be too small to contain mitochondria. However, it is now clear that mitochondria are found throughout fine astrocyte processes and are mobile with neuronal activity resulting in positioning near synapses. In this review, we discuss evidence that astrocytic mitochondria confer selective resiliency to astrocytes during ischemic insults and the functional significance of these mitochondria for normal brain function.
Therapeutic Effect of Long-Term Epidural Block in Rats with Pregnancy Induced Hypertension
Authors: Han Nianjiao , Li Yang , Dong Youjing
Published: February 2018

Background. Pregnancy induced hypertension (PIH) causes a variety of systemic disorders that negatively affect the maternal placenta and fetal growth. Epidural sympathetic block elicits symptoms of decreased blood pressure. This study was designed to determine the therapeutic effect of long-term epidural block in rats with PIH. Methods. Forty healthy pregnant Sprague Dawley rats were randomized into four groups with each group consisting of 10 rats. On gestation day (GD) 14, rats in control group underwent a sham procedure; rats in RUPP group were operated on to obtain reduced uterine perfusion pressure (RUPP); rats in RUPP plus normal saline (NS) group were also subjected to the RUPP procedure and underwent epidural block with 25 μl normal saline twice daily until delivery; rats in RUPP plus epidural block (EB) group were treated as those in RUPP plus NS group except that an epidural block with 25 μl of 0.125% bupivacaine was administered two times per day until delivery. On GD 20, blood pressure was measured in all groups before delivery, and blood samples were collected in order to quantify the serum concentrations of vascular endothelial growth factor (VEGF) and soluble fms-like tyrosine kinase 1 (sFlt-1). Results. The mean arterial pressure (MAP) of rats in RUPP group (147.6±6.0 mmHg) was markedly increased when compared with control group (80.8±4.6 mmHg) (p<0.05). The MAP of rats in RUPP plus EB group (114.4±7.2 mmHg) was clearly decreased in contrast with RUPP group but was still higher than in control group (p<0.05). The variation of fetal weight in all groups followed a similar trend to that of MAP. However, there were no significant differences between control group and RUPP plus EB group with respect to placental weight (p=0.186). Variation in MAP was positively correlated with the expression of sFlt-1 in each group but was negatively correlated with VEGF. Conclusion. This study demonstrates that long-term epidural block decreases blood pressure in PIH rats and improves the serum concentrations of VEGF and sFlt-1. Taken together, long-term epidural block may have a potential role in PIH treatment.
Another Case of De Novo 3q26.33q27.3 Microdeletion and Its Medicolegal Sequel
Authors: Indraccolo Ugo , Indraccolo Salvatore Renato , Fedeli Piergiorgio
Published: February 2018

A new case of a de novo 3q26.33q27.3 microdeletion is reported. The fetus had a sonographically undiagnosable polymalformative syndrome. The case highlights the difficulties of echographic diagnosis of such syndromes and leads to reflection on the difficulties of appropriate counselling in cases of uncertainty.
Fermentation Conditions and Media Optimization for Isocitric Acid Production from Ethanol byYarrowia lipolytica
Authors: Kamzolova Svetlana V. , Shamin Roman V. , Stepanova Nadezda N. , Morgunov Grigorii I. , Lunina Julia N. , Allayarov Ramil K. , Samoilenko Vladimir A. , Morgunov Igor G.
Published: February 2018

Isocitric acid exists in the form of four stereoisomers, of which only thethreo-Ds-form (ICA) is a natural active compound, an intermediate of Krebs cycle, and suitable for nutritional and pharmaceutical use. In this paper, we propose a method for ICA production from ethanol by yeastYarrowia lipolytica. The effects of temperature, pH of the medium, and aeration on the growth of the producerY. lipolyticaVKM Y-2373 and synthesis of ICA were studied. An optimal fermentation regime, which ensures a good growth of the producer and directed synthesis of the target product, was determined. The producer is advised to carry out cultivation at 29°C and various pH of the medium and the oxygen concentration (pH 5 and pO220–25% (of saturation) during the growth period and pH 6 and pO250–55% (of saturation) during the acid formation) on a nutrient medium containing an increased content of zinc (0.6 mg/L), iron (1.2 mg/L), and 30 mM itaconic acid (inhibitor of isocitrate lyase—the key enzyme of ICA metabolism) should also be introduced into the nutrition medium. Such fermentation production mode provides 90.5 g/L ICA with process selectivity of 80%, mass yield (YICA) of 0.77 g/g, and energy yield (ηICA) of 0.278 g/g.
Whole Peptidoglycan Extracts from theLactobacillus paracaseisubsp.paracaseiM5 Strain Exert Anticancer ActivityIn Vitro
Authors: Wang Shumei , Han Xue , Zhang Lanwei , Zhang Yingchun , Li Hongbo , Jiao Yuehua
Published: February 2018

TheLactobacillus paracaseisubsp. paracaseiM5 strain exerted potential anticancer activity through the cell wall. In this study, whole peptidoglycan (WPG) was extracted from theLactobacillus paracaseisubsp. paracaseiM5 strain and was evaluated for anticancer effects as well as its properties. SDS-PAGE analysis confirmed the presence of WPG with dominant bands of approximately 14.4 kDa. Further analysis revealed that the amino acids present in the WPG consisted of alanine, glycine, glutamic acid, and lysine in a molar ratio of approximately 8 : 5 : 3 : 3.5. In addition, the cell viability of HT-29 cells with WPG addition was investigated with methyl thiazolyl tetrazolium (MTT) and trypan blue exclusion (TBE) assays, and cell apoptosis was analyzed with a transmission electron microscope, flow cytometry, and semiquantitative RT-PCR. These results showed that WPG exerted cytotoxic effects on colon cancer HT-29 cells in a dose-dependent manner and upregulated proapoptotic genes, while downregulating antiapoptotic genes. The gene expression study definitively revealed that WPG induced a mitochondria-mediated apoptotic pathway.
Effect of Hemodialysis on Eye Coats, Axial Length, and Ocular Perfusion Pressure in Patients with Chronic Renal Failure
Authors: Wang Ling , Yin Gang , Yu Zhiying , Chen Nan , Wang Dabo
Published: February 2018

Purpose. To investigate changes in eye coats, axial length, and ocular perfusion pressure (OPP) in hemodialysis (HD) patients with chronic renal failure (CRF). Methods. We included HD patients who were diagnosed with CRF in our hospital from January to December 2015. Fifty-two patients met the inclusion criteria; all right eyes were used for observation. Systolic and diastolic blood pressures were recorded to calculate OPP. Approximately 30 minutes before and after HD, we recorded multiple parameters, including lens thickness (LT), axial length of vitreous (VAL), axial length of eye (EAL), ciliary body thickness (CBT), choroidal thickness (CT), and retinal thickness (RT). Results. After HD, OPP significantly decreased (P<0.01, F=7.023) and CBT became significantly thinner (P<0.01, t=3.461). CT was significantly thinner and differed among measurement locations (P<0.01, t=6.240; P<0.01, t=6.169; P<0.01, t=3.405, respectively, fovea, nasal, and temporal side 1500 μm beside the fovea). Further, RT thickened and differed among measurement locations (P<0.05, t=−2.265; P<0.05, t=−2.624; P<0.05, t=−2.220, respectively, fovea, nasal, and temporal side 1500 μm beside fovea), whereas LT, VAL, and EAL significantly increased after HD (P<0.05, t=−2.076; P<0.01, t=−3.817; P<0.01, t=−4.010). Conclusions. HD impacts the thickness of the eye coats and VAL, particularly affecting CBT, CT, and RT. OPP transiently decreases during HD, which may contribute to an ischemic state.
Postactivation Potentiation Following Acute Bouts of Plyometric versus Heavy-Resistance Exercise in Collegiate Soccer Players
Authors: Sharma Sourabh Kumar , Raza Shahid , Moiz Jamal Ali , Verma Shalini , Naqvi Irshad Husain , Anwer Shahnawaz , Alghadir Ahmad H.
Published: February 2018

Postactivation potentiation is referred to as an acute and temporary enhancement of muscle performance resulting from previous muscle contraction. The purpose of this study was to compare the acute effect of plyometric exercise (PLY) and heavy-resistance exercise (RES) on the blood lactate level (BLa) and physical performance. Fourteen male collegiate soccer players were randomized to perform either RES or PLY first and then crossed over to perform the opposite intervention. PLY consisted of 40 jumps, whereas RES comprised ten single repetitions at 90% of one repetition maximum. BLa and physical performance (countermovement jump height and 20-m sprint) were measured before and at 1 and 10 min following the exercise. No significant difference was observed in the BLa for both exercises (PLY and RES). Relative to baseline, countermovement jump (CMJ) height was significantly better for the PLY group after 1 min (P=0.004) and after 10 min (P=0.001) compared to that of the RES group. The 20-m sprint time was significantly better for PLY at 10 min (P=0.003) compared to that of RES. The present study concluded that, compared to RES, PLY causes greater potentiation, which leads to improved physical performance. This trial is registered with NCT03150277.
The Protective Effects of Enalapril Maleate and Folic Acid Tablets against Contrast-Induced Nephropathy in Diabetic Rats
Authors: Hou Jiantong , Yan Gaoliang , Liu Bo , Zhu Boqian , Qiao Yong , Wang Dong , Li Ruifeng , Luo Erfei , Tang Chengchun
Published: February 2018

Background. Renal vasoconstriction, oxidative stress, endothelial dysfunction, and apoptosis are the major causes of contrast-induced nephropathy (CIN). The aim of this study was to evaluate the protective effects of enalapril maleate and folic acid tablets on CIN in diabetic rats.Methods. Thirty-two Sprague-Dawley rats were divided into four groups: CIN (C), CIN + enalapril maleate (CE), CIN + folic acid (CF), and CIN + enalapril maleate and folic acid tablets (CEF). CE, CF, and CEF rats were treated orally with enalapril maleate, folic acid, or enalapril maleate and folic acid tablets, respectively, for 5 days. CIN was induced in all groups followed by analyzed biochemical parameters, oxidative stress markers, endothelial dysfunction parameters, renal histopathology, and TUNEL staining.Results. Serum creatinine, blood urea nitrogen, and malondialdehyde levels were lower in the CEF group than in the C group. Homocysteine, superoxide dismutase, glutathione peroxidase, and nitric oxide levels were higher in the CEF group than in the C group. Histopathology scores and percentage of apoptotic kidney cells in the CEF group were significantly decreased compared with those in the C group.Conclusions. These results suggest that enalapril maleate and folic acid tablets have a protective effect against CIN in diabetic rats.
The Balance of Th1/Th2 and LAP+Tregs/Th17 Cells Is Crucial for Graft Survival in Allogeneic Corneal Transplantation
Authors: Li Shang , Yu Jing , Guo Chungang , Jie Ying , Pan Zhiqiang
Published: February 2018

Purpose. CD4+LAP+ T cells are newly discovered regulatory T cells (Tregs). The aim of this study is to investigate the balance of Th1/Th2 and LAP+Tregs/Th17 in mice after allogeneic corneal transplantation. Methods. A total of 65 mice received orthotopic penetrating transplantation. According to the survival scores of the grafts, the mice were divided into the rejection group and the survival group 3 weeks after transplantation. Th1, Th2, Th17, and regulatory T cells in the ipsilateral drainage lymph nodes and spleens were measured with flow cytometry. The related cytokines in aqueous humor were also analyzed. Results. The frequencies of Foxp3+Tregs, GARP+Tregs, and LAP+Tregs in the survival group were significantly higher than those in the rejection group. And the expression trend of CD4+LAP+ T cells and CD4+GARP+ T cells was consistent. The level of IFN-γ, TNF, IL-6, and IL-17A markedly increased in aqueous humor during corneal allograft rejection. The ratio of Th1/Th2 and Th17/LAP+Tregs significantly increased in the rejection group at the 3rd week after corneal transplantation. Conclusion. LAP+Tregs might be regarded as substitute for Foxp3+Tregs. The balance of Th1/Th2 and LAP+Tregs/Th17 is crucial for corneal allograft survival.
A Robust Control Method for Lateral Stability Control of In‐Wheel Motored Electric Vehicle Based on Sideslip Angle Observer
Authors: Wang Yaxiong , Kang Feng , Wang Taipeng , Ren Hongbin
Published: February 2018

In‐wheel motored powertrain on electric vehicles has more potential in maneuverability and active safety control. This paper investigates the longitudinal and lateral integrated control through the active front steering and yaw moment control systems considering the saturation characteristics of tire forces. To obtain the vehicle sideslip angle of mass center, the virtual lateral tire force sensors are designed based on the unscented Kalman filtering (UKF). And the sideslip angle is estimated by using the dynamics‐based approaches. Moreover, based on the estimated vehicle state information, an upper level control system by using robust control theory is proposed to specify a desired yaw moment and correction front steering angle to work on the electric vehicles. The robustness of proposed algorithm is also analyzed. The wheel torques are distributed optimally by the wheel torque distribution control algorithm. Numerical simulation is carried out in Matlab/Simulink‐Carsim cosimulation environment to demonstrate the effectiveness of the designed robust control algorithm for lateral stability control of in‐wheel motored vehicle.
Experimental Nanopulse Ablation of Multiple Membrane Parasite on Ex Vivo Hydatid Cyst
Authors: Chen Xinhua , Zhang Ruiqing , Wen Hao
Published: February 2018

The impact of ultrashort nanopulse on cellular membrane is of biological significance and thus has been studied intensively. Different from cell study, this ex vivo study aims to investigate the biological effects of nanosecond pulsed electric field (nsPEF) on an independent multimembrane parasite, human hydatid cyst, to observe the unique influence of nanopulse on macromembrane structure, permeabilization, and biochemistry. The 300 ns nsPEF was delivered on an experimental model of single human hydatid cyst ex vivo with eight different parameters. Then pathological changes during 7 days of 48 parasite cysts were followed up after nsPEF. The laminated layer, the germinal layer, the protoscolex, and cyst fluid were evaluated by the morphological, pathological, and biochemical measurements. The parameter screening found that nsPEF can damage hydatid cyst effectively when the field strength is higher than 14 kV/cm. When nsPEF is higher than 29 kV/cm, nsPEF destroy hydatid cyst completely by collapsing the germinal layer, destructing protoscolices, and exhausting the nutrition.
A Two-Step Feature Selection Method to Predict Cancerlectins by Multiview Features and Synthetic Minority Oversampling Technique
Authors: Yang Runtao , Zhang Chengjin , Zhang Lina , Gao Rui
Published: February 2018

Cancerlectins have an inhibitory effect on the growth of cancer cells and are currently being employed as therapeutic agents. The accurate identification of the cancerlectins should provide insight into the molecular mechanisms of cancers. In this study, a new computational method based on the RF (Random Forest) algorithm is proposed for further improving the performance of identifying cancerlectins. Hybrid feature space before feature selection is developed by combining different individual feature spaces, CTD (Composition, Transition, and Distribution), PseAAC (Pseudo Amino Acid Composition), PSSM (Position-Specific Scoring Matrix), and disorder. The SMOTE (Synthetic Minority Oversampling Technique) is applied to solve the imbalanced data problem. To reduce feature redundancy and computation complexity, we propose a two-step feature selection process to select informative features. A 5-fold cross-validation technique is used for the evaluation of various prediction strategies. The proposed method achieves a sensitivity of 0.779, a specificity of 0.717, an accuracy of 0.748, and an MCC (Matthew’s Correlation Coefficient) of 0.497. The prediction results are also compared with other existing methods on the same dataset using 5-fold cross-validation. The comparison results demonstrate the high effectiveness of our method for predicting cancerlectins.
Investigations on Driver Unique Identification from Smartphone’s GPS Data Alone
Authors: Chowdhury Arijit , Chakravarty Tapas , Ghose Avik , Banerjee Tanushree , Balamuralidhar P.
Published: February 2018

Driver identification is an emerging area of interest in vehicle telematics, automobile control, and insurance. Recent body of works indicates that it may be possible to uniquely identify a driver using multiple dedicated sensors. In this paper, we present an approach for driver identification using smartphone GPS data alone. For our experiments, we collected data from 38 drivers for two months. We quantified the driver’s natural style by extracting a set of 137 statistical features from data generated for each completed trip. The analysis shows that, for the “driver identification” problem, an average accuracy of 82.3% is achieved for driver groups of 4-5 drivers. This is comparable to the state of the arts where mostly a multisensor approach has been taken. Further, it is shown that certain behavioral attributes like high driving skill impact identification accuracy. We observe that Random Forest classifier offers the best results. These results have great implications for various stakeholders since the proposed method can identify a driver based on his/her naturalistic driving style which is quantified in terms of statistical parameters extracted from only GPS data.
The Role of Toll-Like Receptor Signaling in the Progression of Heart Failure
Authors: Yu Lili , Feng Zhiwei
Published: February 2018

Medical systems worldwide are being faced with a growing need to understand mechanisms behind the pathogenesis of heart failure (HF) that is considered as a leading cause of morbidity and mortality around the world. Elevated levels of inflammatory mediators have been identified in patients with HF, which are primarily manifestations of innate immune responses mediated by pattern recognition receptors (PRRs). Toll-like receptors (TLRs), which belong to PRRs, are subjected to the release of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) to generate innate immune responses. More and more emerging data indicate that TLR signaling pathway molecules are involved in the progression of HF. Herein, we present new data with regard to the activation of TLRs in the failing heart, focusing on TLR2, TLR3, TLR4, and TLR9, and suggest the potential use of TLRs in target therapy.
The Patient's Experience of Ocular Melanoma in the US: A Survey of the Ocular Melanoma Foundation
Authors: Afshar Armin R. , Deiner Michael , Allen Grant , Damato Bertil E.
Published: February 2018

Background: Ocular melanomas threaten patients with early death, visual handicap, and loss of the eye. The aims of this study were to identify aspects of care that patients with ocular melanoma considered most important and to determine whether patients felt their needs had been adequately addressed. Methods: A cross-sectional study including US ocular melanoma patients and their caregivers. An online survey of US ocular melanoma patients was designed and conducted by the Ocular Melanoma Foundation. Results: The cohort included 180 patients with uveal melanoma and 4 with conjunctival melanoma. Median follow-up was 3 years. A third of patients reported that their uveal melanoma had initially been diagnosed as a nevus. Most uveal melanomas were treated with brachytherapy. Almost 50% of patients had no genetic tumor analysis. Screening methods reported most commonly were computed tomography and liver function tests. Metastatic disease developed in 11% of patients. Few patients (13.3%) reported an offer of psychological support. Most dissatisfaction was with lack of advice on financial aspects of care and lack of psychological counseling, with women tending to express more dissatisfaction with care. Many patients complained about the way ophthalmologists delivered bad news to them. Conclusions: This patients' perspective highlights directions for research, education, and other measures to improve the care of patients with ocular melanoma in the US and elsewhere.
Pathophysiology of Functional Gastrointestinal Disorders: A Holistic Overview
Authors: Holtmann Gerald , Shah Ayesha , Morrison Mark
Published: February 2018

Background and Summary: Traditionally, functional gastrointestinal disorders (FGID), including functional dyspepsia or irritable bowel syndrome (IBS), are defined by more or less specific symptoms and the absence of structural or biochemical abnormalities that cause these symptoms. This concept is now considered to be outdated; if appropriate tests are applied, structural or biochemical abnormalities that explain or cause the symptoms may be found in many patients. Another feature of FGID are the highly prevalent psychiatric comorbidities, such as depression and anxiety. It is implied that mood disorders “cause” gastrointestinal symptoms. In fact, epidemiological data now provide strong evidence that in subsets of cases, gastrointestinal (GI) symptoms arise first and mood disorders occur later, while in other patients the reverse appears to happen. Possible mechanisms for gut-brain dysfunction have been identified, with systemic minimal inflammation as a causal factor in at least some subjects. Other mechanisms that play a role in FGID include chronic infections, intestinal microbiota, low-grade mucosal inflammation including the increase of eosinophils, systemic immune activation, altered intestinal permeability, in diarrhea predominant IBS altered bile salt metabolism, abnormalities in the serotonin metabolism and genetic factors. All these factors might be modulated by environmental factors such as diet. Key Messages: While a number of factors can be linked to specific symptoms (e.g., pain or diarrhea), it is evident that the symptom-based categorization of patients will not allow targeted treatments that specifically address the underlying pathophysiology.
Remineralization Potential of Mints Containing Bioactive Agents in Artificially Induced Root Caries
Authors: Zamperini Camila A. , Bedran-Russo Ana K.
Published: February 2018

This study investigated the remineralization effect of experimental mint formulations containing bioactive agents (xylitol; green tea extract, GT; and amorphous calcium phosphate, ACP) in the progression of artificially induced root caries. Root caries lesions were induced by demineralization solution (pH 4.6; 96 h; 37°C). The lesions were treated with mint A, mint B, mint C, xylitol, GT, ACP, or remineralization solution (RS; negative control). Specimens were pH-cycled through treatments (5×/day; 3 min) and 6 cycles of acidic (pH 5.0; 30 min) and neutral (pH 7.0; 10 min) buffers for 8 days. Bacterial collagenase (Clostridium histolyticum) was used overnight to simulate proteolytic challenge. Caries depth and porosity as well as mineral density were estimated using fluorescence microscopy (n = 15) and microcomputed tomography (n = 6). Analysis of variance (ANOVA, α = 0.05) showed no statistically significant difference in caries depth among all groups (p = 0.172). The highest fluorescence intensity decrease was observed for GT followed by mint C, with no significant difference between them (p = 0.868). There were significant differences among GT and mints A, B, and C when compared to RS (p < 0.001). No statistically significant differences in fluorescence intensity were observed among ACP, xylitol, and RS (p > 0.05). The mineral density of the lesions in GT, mints A, B, and C, and ACP was statistically similar (p > 0.05) and significantly higher than that in RS (p < 0.05). No significant difference was observed between xylitol and RS (p = 0.728). The experimental mints showed remineralization action on artificial root caries, and GT was found to be the main active ingredient in the investigated formulations.
Pulmonary Diseases in Refugees and Migrants in Europe
Authors: Olaru Ioana D. , Van Den Broucke Steven , Rosser Andrew J. , Salzer Helmut J.F. , Woltmann Gerrit , Bottieau Emmanuel , Lange Christoph
Published: February 2018

More than 2 million people fleeing conflict, persecution, and poverty applied for asylum between 2015 and 2016 in the European Union. Due to this, medical practitioners in recipient countries may be facing a broader spectrum of conditions and unusual presentations not previously encountered, including a wide range of infections with pulmonary involvement. Tuberculosis is known to be more common in migrants and has been covered broadly in other publications. The scope of this review was to provide an overview of exotic infections with pulmonary involvement that could be encountered in refugees and migrants and to briefly describe their epidemiology, diagnosis, and management. As refugees and migrants travel from numerous countries and continents, it is important to be aware of the various organisms that might cause disease according to the country of origin. Some of these diseases are very rare and geographically restricted to certain regions, while others have a more cosmopolitan distribution. Also, the spectrum of severity of these infections can vary from very benign to severe and even life-threatening. We will also describe infectious and noninfectious complications that can be associated with HIV infection as some migrants might originate from high HIV prevalence countries in sub-Saharan Africa. As the diagnosis and treatment of these diseases can be challenging in certain situations, patients with suspected infection might require referral to specialized centers with experience in their management. Additionally, a brief description of noncommunicable pulmonary diseases will be provided.
Delirium, Frailty, and Fast-Track Surgery in Oncogeriatrics: Is There a Link?
Authors: Monacelli Fiammetta , Signori Alessio , Prefumo Matteo , Giannotti Chiara , Nencioni Alessio , Romairone Emanuele , Scabini Stefano , Odetti Patrizio
Published: February 2018

Background/Aims: Postoperative delirium (POD) is more frequent in elderly patients undergoing major cancer surgery. The interplay between individual clinical vulnerability and a series of perioperative factors seems to play a relevant role. Surgery is the first-line treatment option for cancer, and fast-track surgery (FTS) has been documented to decrease postoperative complications. The study sought to assess, after comprehensive geriatric assessment (CGA) and frailty stratification (Rockwood 40 items index), which perioperative parameters were predictive of POD development in elderly patients undergoing FTS for colorectal cancer. Methods: A total of 107 consecutive subjects admitted for elective colorectal FTS were enrolled. All patients underwent CGA, frailly stratification, Timed up & go (TUG) test, 4AT test for delirium screening, anesthesiologists physical status classification, and Dindo-Clavien classification. Results: The incidence of POD was 12.3%. Patients’ prevalent clinical phenotype was pre-frail. The multivariate analysis indicated physical performance (TUG in seconds) as the most significant predictor of POD for each second of increase. Conclusions: Only few procedure-specific studies have examined the impact of FTS for colorectal cancer on POD. This is the first study to investigate the risk factors for POD, in a vulnerable octogenarian oncogeriatric population submitted to FTS surgery and frailty stratification.
Prognostic Significance of Pre- and Postoperative Lymphocyte Counts in Patients with Gastric Cancer
Authors: Saito Hiroaki , Kono Yusuke , Murakami Yuki , Shishido Yuji , Kuroda Hirohiko , Yamamoto Manabu , Fukumoto Yoji , Osaki Tomohiro , Ashida Keigo , Fujiwara Yoshiyuki
Published: February 2018

Background: Although preoperative lymphopenia is reportedly a prognostic factor in cancer patients, the association between postoperative lymphopenia and patient prognosis has not been widely studied. Methods: We enrolled 352 patients who underwent surgery for gastric cancer (GC) between January 2005 and April 2013 to analyze correlations among pre- and postoperative lymphocyte counts (LCs) and prognosis in GC patients. Results: Pre- and postoperative (obtained 1 day after surgery) LCs were significantly correlated (r = 0.496, p < 0.0001). Pre- and postoperative LCs of elderly patients were significantly lower than those of non-elderly patients. Postoperative lymphocyte count was significantly lower in patients with a differentiated tumor than in those with an undifferentiated tumor. Based on the results of receiver operating characteristic analysis, patients were classified into subgroups as: preoperative LC ≥1,676 (pre-LCHigh), preoperative LC <1,676 (pre-LCLow); and as postoperative LC ≥855 (post-LCHigh), and postoperative LC <855 (post-LCLow). Five-year overall survival rates significantly differed between pre-LCHigh (82.5%) and pre-LCLow (71.6%) groups (p = 0.023); and also between the post-LCHigh (81.5%) and post-LCLow (69.5%) groups (p = 0.0072). The 5-year disease specific survival rates were 91.3 and 82.4% in patients with post-LCHigh and those with post-LCLow, respectively, and differences were statistically significant (p = 0.015). Multivariate analysis indicated that postoperative lymphocyte count was an independent prognostic indicator, along with age, gender, tumor size, lymph node metastasis, and venous invasion. Conclusions: Postoperative lymphocyte count is a useful predictive factor for prognosis in GC patients.
Edgar Adrian (1889–1977) and Shell Shock Electrotherapy: A Forgotten History?
Authors: Tatu Laurent
Published: February 2018

The English electrophysiologist Edgar Adrian (1889–1977) was the recipient of the Nobel Prize for physiology in 1932 for his research on the functions of neurons. During World War I, at Queen Square in London, he devised an intensive electrotherapeutic treatment for shell-shocked soldiers. The procedure, developed with Lewis Yealland (1884–1954), was similar to “torpillage,” the faradic psychotherapy used in France. Adrian and Yealland considered that the pain accompanying the use of faradic current was necessary for both therapeutic and disciplinary reasons, especially because of the suspicion of malingering. According to Adrian, this controversial electric treatment was only able to remove motor or sensitive symptoms. After the war, he finally admitted that war hysteria was a complex and difficult phenomenon.
An International Genetic Survey of Breed-Specific Diseases in Working Dogs from the United States, Israel, and Poland
Authors: Shaffer Lisa G. , Ramirez Christina J. , Phelps Patricia , Aviram Maya , Walczak Marta , Bar-Gal Gila Kahila , Ballif Blake C.
Published: February 2018

Genetic diseases occur in breeds used for law enforcement. As important team members, dogs are expected to operate at peak performance for several years and are significant investments for both the initial purchase and extensive, specialized training. Previous studies have not focused on causes for retirement or euthanasia as genetic (inherited) versus acquired (environmental). We performed direct mutational analysis for breed-specific conditions on samples from 304 dogs including 267 law enforcement (122 US, 87 Israeli, and 58 Polish) and 37 search and rescue dogs. Genetic testing identified 29% (n = 89) of the dogs tested to be carriers of a genetic mutation and 6% (n = 19) to be at risk for a debilitating inherited condition that may eventually impair the dog's ability to work. At-risk dogs included Labrador Retrievers (n = 4) with exercise-induced collapse, Bloodhounds (n = 2) with degenerative myelopathy (DM), and German Shepherd dogs with DM (n = 12) or leukocyte adhesion deficiency, type III (n = 1). A substantial number of working dogs were shown to be at risk for genetic conditions that may shorten the dog's career. The loss of dogs, due to early retirement or euthanasia, as a result of preventable genetic conditions has an emotional cost to handlers and financial cost to service organizations that can be avoided with genetic screening prior to breeding, buying, or training.
Expression Profiling Identifies Circular RNA Signature in Hepatoblastoma
Authors: Liu Bai-Hui , Zhang Bin-Bin , Liu Xiang-Qi , Zheng Shan , Dong Kui-Ran , Dong Rui
Published: February 2018

Background/Aims: Hepatoblastoma is the most common malignant pediatric liver cancer. circular RNAs (circRNAs) play important roles in fine-tuning gene expression and are often deregulated in cancers. However, the expression profile and clinical significance of circRNAs in hepatoblastoma is still unknown. Methods: Circular RNA microarray was conducted to identify hepatoblastoma-related circRNAs. GO analysis, pathway analysis, and miRNA response elements analysis was conducted to predict the potential roles of differentially expressed circRNAs in hepatoblastoma. MTT assays, Ki67 staining, and Transwell assays were conducted to clarify the role of circRNA in hepatoblastoma in vitro. Bioinformatics analysis and in vitro experiments were conducted to clarify the mechanism of circRNA-mediated gene regulation in hepatoblastoma cell. Results: 869 differentially expressed circRNAs were identified between hepatoblastoma and adjacent normal liver samples, including 421 up-regulated circRNAs and 448 down-regulated circRNAs. The significant enriched GO term of hepatoblastoma-related circRNAs in biological process, cellular component, and molecular function were “chromosome organization”, “cytoplasm”, and “organic cyclic compound binding”. Tight junction signaling pathway was ranked the Top 1 potentially affected by circRNA-mediated regulatory network. circ_0015756 was significantly up-regulated in human hepatoblastoma specimens and metastatic hepatoblastoma cell lines. circ_0015756 silencing decreased hepatoblastoma cell viability, proliferation, and invasion in vitro. circ_0015756 acted as miR-1250-3p sponge to regulate hepatoblastoma cell function. Conclusions: circRNAs are involved in the pathogenesis of hepatoblastoma. circ_0015756 is a promising target for the prognosis, diagnosis, and treatment of hepatoblastoma.
Interference with PSMB4 Expression Exerts an Anti-Tumor Effect by Decreasing the Invasion and Proliferation of Human Glioblastoma Cells
Authors: Cheng Yu-Chen , Tsai Wen-Chiuan , Sung Yu-Chi , Chang Hsin-Han , Chen Ying
Published: February 2018

Background/Aims: Glioblastoma (GBM) is a malignant brain tumor with a poor prognosis. Proteasome subunit beta type-4 (PSMB4) is an essential subunit that contributes to the assembly of the 20S proteasome complex. However, the role of PSMB4 in glioblastomas remains to be clarified. The aim of this study was to investigate the role of PSMB4 in GBM tumor progression. Methods: We first analyzed the PSMB4 protein and mRNA expression in 80 clinical brain specimens and 77 datasets from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. Next, we inhibited the PSMB4 expression by siRNA in cellular and animal models to explore PSMB4’s underlying mechanisms. The cell survival after siPSMB4 transfection was assayed by MTT assay. Annexin V and propidium iodide staining was used to monitor the apoptosis by flow cytometric analysis. Moreover, the migration and invasion were evaluated by wound healing and Transwell assays. The expression of migration-related and invasion-related proteins after PSMB4 inhibition was detected by Western blotting. In addition, an orthotropic xenograft mouse model was used to assay the effect of PSMB4 knockdown in the in vivo study. Results: Basis on the results of bioinformatics study, glioma patients with higher PSMB4 expression had a shorter survival time than those with lower PSMB4 expression. The staining of clinical brain tissues showed elevated PSMB4 expression in GBM tissues compared with normal brain tissues. The PSMB4 inhibition decreased proliferation, migration and invasion abilities in human GBM cells. Downregulated PSMB4 resulted in cell cycle arrest and apoptosis in vitro. In an orthotropic xenograft mouse model, the glioma tumors progression was reduced when PSMB4 was down-regulated. The decreased PSMB4 enhanced the anti-tumor effect of temozolomide (TMZ) on tumor growth. In addition, the absence of PSMB4 decreased the expression of phosphorylated focal adhesion kinase and matrix metallopeptidase 9 in vivo. Conclusion: PSMB4 inhibition in combination with TMZ may exert an anti-tumor effect by decreasing cell proliferation and invasion as well as by promoting apoptosis in human glioblastoma cells. This research may improve the therapeutic efficacy of glioblastoma treatment.
Swiprosin-1 Promotes Mitochondria-Dependent Apoptosis of Glomerular Podocytes via P38 MAPK Pathway in Early-Stage Diabetic Nephropathy
Authors: Wang Rong-Mei , Wang Zhi-Bin , Wang Yue , Liu Wei-Ye , Li Ya , Tong Ling-Chang , Zhang Su , Su Ding-Feng , Cao Yong-Bing , Li Ling , Zhang Li-Chao
Published: February 2018

Background/Aims: Podocyte injury, especially podocyte apoptosis, plays a major role in early-stage diabetic nephropathy (DN). Swiprosin-1, also known as EF hand domain containing 2 (EFhd2), is a Ca2+-binding protein in different cell types. However, the function of swiprosin-1 in podocytes remains unknown. Methods: The expression and distribution of swiprosin-1 were investigated in the mouse renal glomerulus and conditionally immortalized mouse podocyte cell line MPC-5. The expression of swiprosin-1 was also detected in streptozotocin (STZ)-treated mice and MPC-5 cells treated with high glucose (HG). Nephrin and podocin were detected by immunohistochemistry and immunofluroscence. Collagen IV, transforming growth factor-β (TGF-β) and fibronectin mRNA expressions were assayed by real-time PCR. Apoptotic proteins and phosphorylation of p38 mitogen-activated protein kinase (MAPK) were detected by immunoblotting. Results: Swiprosin-1 was found to be expressed in podocytes of the mouse glomerulus and MPC-5 cells. Swiprosin-1 expression was increased in STZ-treated mice and MPC-5 cells treated with HG. In Swiprosin-1-/- diabetic mice, kidney/ body weight, urinary albumin, podocyte foot process effacement and glomerular basement membrane thickening were attenuated; the downregulation of nephrin and podocin expression in the glomerulus was inhibited; and the upregulation of collagen IV, TGF-β and fibronectin mRNA expression in the renal cortex was ameliorated as compared with those in diabetic swiprosin-1+/+ mice. In addition, the increased apoptosis of podocytes, proapoptotic protein expression and p38 phosphorylation in Swiprosin-1-/- diabetic mice were inhibited as compared with those in diabetic swiprosin-1+/+ mice. Knockdown of swiprosin-1 in MPC-5 cells reduced the apoptosis of podocytes, proapoptotic protein expression and p38 phosphorylation induced by HG. Targeted knockdown of p38 attenuated the increased apoptosis of MPC-5 cells over-expressing swiprosin-1. Conclusion: Swiprosin-1 expression in podocytes of the mouse glomerulus played a critical role in early-stage DN. Swiprosin-1 deficiency in early DN attenuated mitochondria-dependent podocyte apoptosis induced by hyperglycemia or HG via p38 MAPK signaling pathway.
ПСИХОЛОГІЧНИЙ ПОРТРЕТ СІМЕЙНОГО КОНФЛІКТУ
Authors: Krugla T. O.
Published: February 2018

У статті розкрито поняття подружнього конфлікту. Проаналізовано погляди вчених, які займалися вивченням даної проблеми. Представлені результати дослідження дозволяють стверджувати про актуальність та доцільність розпочатої науково-дослідницької роботи.
ОСОБЛИВОСТІ СИНДРОМУ ЕМОЦІЙНОГО ВИГОРАННЯ У МЕДИЧНИХ ПРАЦІВНИКІВ
Authors: Draga T. M. , Myaluk O. P. , Krynytska I. Ya.
Published: February 2018

У статті розглянуто сучасні теоретичні підходи до синдрому емоційного вигорання як форми професійної деформації медичних працівників. Звернено увагу на фактори, що викликають вигорання та фази розвитку синдрому емоційного вигорання.