bluuebunny/crossref_metadata_2025 huggingface dataset:
Achieving comparable perfusion results across vendors. The next step in standardizing stroke care: a technical report
Authors: Bathla Girish , Limaye Kaustubh , Policeni Bruno , Klotz Ernst , Juergens Markus , Derdeyn Colin
Published: May 2019

Background

The role of mechanical thrombectomy in acute ischemic stroke (AIS) has been further expanded by recent trials which relied on the results of CT perfusion (CTP) imaging. However, CTP parameters for ischemia and infarct can vary significantly across different vendors.

Methods

We compared the outcomes of the Siemens CTP software against the clinically validated RAPID software in 45 consecutive patients with suspected AIS. Both perfusion softwares initially processed images using vendor defined parameters for hypoperfusion and non-viable tissue. The software thresholds on the Siemens software were decrementally altered to see if concordant results between softwares could be attained.

Results

At baseline settings, the mean values for core infarct and hypoperfusion were different (mean of 30/69 mL, respectively, for RAPID and 49/77 mL for Siemens). However, reducing the threshold values for the later software showed a concordance of values at a relative cerebral blood flow <20%, with resulting core infarct and hypoperfusion volumes at 31/69 mL, respectively, for the Siemens software. A Wilcoxon paired test showed no significant difference between the calculated core infarct and hypoperfusion values, both for the entire population as well as for the subgroup of patients with large vessel occlusion.

Conclusion

Equivalent CTP results between vendor softwares may be attainable by altering the thresholds for hypoperfused and non-viable tissue, despite differences in acquisition techniques, post-processing, and scanners.
Ketogenic diet in combination with voluntary exercise impacts markers of hepatic metabolism and oxidative stress in male and female Wistar rats
Authors: Moore Mary P. , Cunningham Rory P. , Kelty Taylor J. , Boccardi Luigi R. , Nguyen Nhu Y. , Booth Frank W. , Rector R. Scott
Published: May 2019

Ketogenic diets (KDs) are shown to benefit hepatic metabolism; however, their effect on the liver when combined with exercise is unknown. We investigated the effects of a KD versus a “western” diet (WD) on markers of hepatic lipid metabolism and oxidative stress in exercising rats. Male and female Wistar rats with access to voluntary running wheels were randomized to 3 groups (n = 8–14 per group): standard chow (SC; 17% fat), WD (42% fat), or KD (90.5% fat) for 7 weeks. Body fat percentage (BF%) was increased in WD and KD versus SC, although KD females displayed lower BF% versus WD (p ≤ 0.05). Liver triglycerides were higher in KD and WD versus SC but were attenuated in KD females versus WD (p ≤ 0.05). KD suppressed hepatic markers of de novo lipogenesis (fatty acid synthase, acetyl coenzyme A carboxylase) and increased markers of mitochondrial biogenesis/content (peroxisome proliferator activated receptor-1α, mitochondrial transcription factor A (TFAM), and citrate synthase activity). KD also increased hepatic glutathione peroxidase 1 and lowered oxidized glutathione. Female rats exhibited elevated hepatic markers of mitochondrial biogenesis (TFAM), mitophagy (light chain 3 II/I ratio, autophagy-related protein 12:5), and cellular energy homeostasis (phosphorylated 5′AMP-activated protein kinase/5′AMP-activated protein kinase) versus males. These data highlight that KD and exercise beneficially impacts hepatic metabolism and oxidative stress and merits further investigation.

Novelty KD feeding combined with exercise improved hepatic oxidative stress, suppressed markers of de novo lipogenesis, and increased markers of mitochondrial content versus WD feeding. Males and females responded similarly to combined KD feeding and exercise. Female rats exhibited elevated hepatic markers of autophagy/mitophagy and energy homeostasis compared with male rats.
Sitagliptin protects diabetic rats with acute myocardial infarction through induction of angiogenesis: role of IGF-1 and VEGF
Authors: Khodeer Dina M. , Bilasy Shymaa E. , Farag Noha E. , Mehana Amir E. , Elbaz Amani A.
Published: May 2019

Angiogenesis is regulated in a tissue-specific manner in all patients, especially those with diabetes. In this study, we describe a novel molecular pathway of angiogenesis regulation in diabetic rats with myocardial infarction (MI) and examine the cardioprotective effects of different doses of sitagliptin. Male rats were divided into 5 groups: normal vehicle group, diabetic group, diabetic + MI, diabetic + MI + 5 mg/kg sitagliptin, and diabetic + MI + 10 mg/kg sitagliptin. Isoproterenol in diabetic rats resulted in significant (p < 0.05) disturbance to the electrocardiogram, cardiac histopathological manifestations, and an increase in inflammatory markers compared with the vehicle and diabetic groups. Treatment with sitagliptin improved the electrocardiogram and histopathological sections, upregulated vascular endothelial growth factor (VEGF) and transmembrane phosphoglycoprotein protein (CD34) in cardiac tissues, and increased serum insulin-like growth factor 1 (IGF-1) and decreased cardiac tissue homogenate for interleukin 6 (IL-6) and cyclooxygenase 2 (COX-2). A relationship was found between serum IGF-1 and cardiac VEGF and CD34 accompanied by an improvement in cardiac function of diabetic rats with MI. Therefore, the observed effects of sitagliptin occurred at least partly through an improvement in angiogenesis and the mitigation of inflammation. Consequently, these data suggest that sitagliptin may contribute, in a dose-dependent manner, to protection against acute MI in diabetic individuals.
AN EMPIRICAL STUDY ON THE GENDER DIFFERENCES FOR SELF-ORGANIZED ENTREPRENEURIAL BEHAVIOR BASED ON GROUNDED THEORY: A CASE FROM JIANGSU, CHINA
Authors: LI CAI , MAKHDOOM HABIB UR REHMAN , YI LIU
Published: May 2019

Based on grounded theory and combined with empirical investigation of self-organized entrepreneurial behavior, we explored the difference between male and female’s cognitive mode, cognitive bias and behavior influence. It is found that the cognitive pattern of self-organized female entrepreneurs is more narrow and obtrusive, but a few outstanding female entrepreneurs show outstanding performance. Self-organized male entrepreneurs show open and divergent structured cognition. On cognitive bias, women of ordinary self-organized entrepreneurs have a greater range of deviations. In terms of behavior influence, self-organized male entrepreneurs are strongly dependent on prior cognition due to their more emphasis on their professional and technological foundation, and their behavior is more persistent.
Involvement of DHX9/YB-1 complex induced alternative splicing of Krüppel-like factor 5 mRNA in phenotypic transformation of vascular smooth muscle cells
Authors: Huan Wei , Zhang Jing , Li Yingke , Zhi Kangkang
Published: May 2019

Phenotypic transformation of vascular smooth muscle cells is a key phenomenon in the development of aortic dissection disease. However, the molecular mechanisms underlying this phenomenon have not been fully understood. We used β-BAPN combined with ANG II treatment to establish a disease model of acute aortic dissection (AAD) in mice. We first examined the gene expression profile of aortic tissue in mice with AAD using a gene chip, followed by confirmation of DExH-box helicase 9 (DHX9) expression using RT-PCR, Western blot, and immunofluorescence analysis. We further developed vascular smooth muscle cell-specific DHX9 conditional knockout mice and conducted differential and functional analysis of gene expression and alternative splicing in mouse vascular smooth muscle cells. Finally, we examined the involvement of DHX9 in Krüppel-like factor 5 ( KLF5) mRNA alternative splicing. Our study reported a significant decrease in the expression of DHX9 in the vascular smooth muscle cells (VSMCs) of mice with AAD. The smooth muscle cell-specific knockout of DHX9 exacerbated the development of AAD and altered the transcriptional level expression of many smooth muscle cell phenotype-related genes. Finally, we reported that DHX9 may induce alternative splicing of KLF5 mRNA by bridging YB-1. These results together suggested a new pathogenic mechanism underlying the development of AAD, and future research of this mechanism may help identify effective therapeutic intervention for AAD.
Zinc deficiency promotes endothelin secretion and endothelial cell migration through nuclear hypoxia-inducible factor-1 translocation
Authors: Morand Jessica , Briançon-Marjollet Anne , Lemarie Emeline , Gonthier Brigitte , Arnaud Josiane , Korichneva Irina , Godin-Ribuot Diane
Published: May 2019

Zinc is involved in the expression and function of various transcription factors, including the hypoxia-inducible factor-1 (HIF-1). HIF-1 and its target gene endothelin-1 (ET-1) are activated by intermittent hypoxia (IH), one of the main consequences of obstructive sleep apnea (OSA), and both play a key role in the cardiovascular consequences of IH. Because OSA and IH are associated with zinc deficiency, we investigated the effect of zinc deficiency caused by chelation on the HIF-1/ET-1 pathway and its functional consequences in endothelial cells. Primary human microvascular endothelial cells (HMVEC) were incubated with submicromolar doses of the zinc-specific membrane-permeable chelator N, N, N′, N′-tetrakis(2-pyridylmethyl)-ethylene diamine (TPEN, 0.5 µM) or ET-1 (0.01 µM) with or without bosentan, a dual ET-1-receptor antagonist. HIF-1α expression was silenced by transfection with specific siRNA. Nuclear HIF-1 content was assessed by immunofluorescence microscopy and Western blot. Migratory capacity of HMVEC was evaluated with a wound-healing scratch assay. Zinc chelation by TPEN exposure induced the translocation of the cytosolic HIF-1α subunit of HIF-1 to the nucleus as well as an HIF-1-mediated ET-1 secretion by HMVEC. Incubation with either TPEN or ET-1 increased endothelial wound-healing capacity. Both HIF-1α silencing or bosentan abolished this effect. Altogether, these results suggest that zinc deficiency upregulates ET-1 signaling through HIF-1 activation and stimulates endothelial cell migration, suggesting an important role of zinc in the vascular consequences of IH and OSA mediated by HIF-1-ET- signaling.
Disrupted apolipoprotein L1-miR193a axis dedifferentiates podocytes through autophagy blockade in an APOL1 risk milieu
Authors: Kumar Vinod , Ayasolla Kamesh , Jha Alok , Mishra Abheepsa , Vashistha Himanshu , Lan Xiqian , Qayyum Maleeha , Chinnapaka Sushma , Purohit Richa , Mikulak Joanna , Saleem Moin A. , Malhotra Ashwani , Skorecki Karl , Singhal Pravin C.
Published: May 2019

We hypothesized that a functional apolipoprotein LI (APOL1)-miR193a axis (inverse relationship) preserves, but disruption alters, the podocyte molecular phenotype through the modulation of autophagy flux. Podocyte-expressing APOL1G0 (G0-podocytes) showed downregulation but podocyte-expressing APOL1G1 (G1-podocytes) and APOL1G2 (G2-podocytes) displayed enhanced miR193a expression. G0-, G1-, and G2-podocytes showed enhanced expression of light chain (LC) 3-II and beclin-1, but a disparate expression of p62 (low in wild-type but high in risk alleles). G0-podocytes showed enhanced, whereas G1- and G2-podocytes displayed decreased, phosphorylation of Unc-51-like autophagy-activating kinase (ULK)1 and class III phosphatidylinositol 3-kinase (PI3KC3). Podocytes overexpressing miR193a (miR193a-podocytes), G1, and G2 showed decreased transcription of PIK3R3 (PI3KC3′s regulatory unit). Since 3-methyladenine (3-MA) enhanced miR193a expression but inhibited PIK3R3 transcription, it appears that 3-MA inhibits autophagy and induces podocyte dedifferentiation via miR193a generation. miR193a-, G1-, and G2-podocytes also showed decreased phosphorylation of mammalian target of rapamycin (mTOR) that could repress lysosome reformation. G1- and G2-podocytes showed enhanced expression of run domain beclin-1-interacting and cysteine-rich domain-containing protein (Rubicon); however, its silencing prevented their dedifferentiation. Docking, protein-protein interaction, and immunoprecipitation studies with antiautophagy-related gene (ATG)14L, anti-UV radiation resistance‐associated gene (UVRAG), or Rubicon antibodies suggested the formation of ATG14L complex I and UVRAG complex II in G0-podocytes and the formation of Rubicon complex III in G1- and G2-podocytes. These findings suggest that the APOL1 risk alleles favor podocyte dedifferentiation through blockade of multiple autophagy pathways.
Anaphylaxis stimulates afferent vagal nerve activity and efferent sympathetic nerve activity in the stomach of anesthetized rats
Authors: Kuda Yuhichi , Tanida Mamoru , Chen Fu , Kurata Yasutaka , Shibamoto Toshishige
Published: May 2019

Systemic anaphylaxis is a life-threatening and allergic reaction that affects various organs. We previously reported that, in the stomach, gastric vasoconstriction occurring at the late phase (15–55 min after injection of ovalbumin antigen) was observed in anesthetized rats sensitized with ovalbumin. In addition, anaphylaxis enhances gastric motility and delays emptying. However, the role of extrinsic autonomic nervous system on antigen-induced gastric alterations was not known. Thus, using the same rat anaphylaxis model, we aimed to determine the changes in the efferent and afferent autonomic nerve activities in the stomach during anaphylactic hypotension. The findings showed that injection of ovalbumin antigen caused substantial systemic hypotension in all sensitized rats. The efferent gastric sympathetic nerve activity (ef-GSNA), but not the efferent vagal nerve activity, increased only at the early phase (1–10 min after injection of ovalbumin antigen) and showed baroreceptor reflex, as evidenced by a stimulatory response to sodium nitroprusside-induced hypotension. In general, excitation of ef-GSNA could induce pylorus sphincter contraction and gastric vasoconstriction. In the present study, we found that sympathectomy attenuated the anaphylaxis-induced decrease in gastric flux but not the increase in gastric vascular resistance. Thus, the increase in ef-GSNA may cause anaphylactic pylorus sphincter contraction but not anaphylactic gastric vasoconstriction. On the other hand, the afferent gastric vagal nerve activity, but not the afferent sympathetic nerve activity, increased during the early phase of anaphylactic hypotension. However, vagotomy produced no effects on the anaphylactic gastric dysfunction. In conclusion, the gastric sympathetic nerves partly modulate stomach function during systemic anaphylaxis.
Nicotinic acetylcholine receptor subunit α7-knockout mice exhibit degraded auditory temporal processing
Authors: Felix Richard A. , Chavez Vicente A. , Novicio Dyana M. , Morley Barbara J. , Portfors Christine V.
Published: May 2019

The CHRNA7 gene that encodes the α7-subunit of the nicotinic acetylcholine receptor (α7-nAChR) has been associated with some autism spectrum disorders and other neurodevelopmental conditions characterized, in part, by auditory and language impairment. These conditions may include auditory processing disorders that represent impaired timing of neural activity, often accompanied by problems understanding speech. Here, we measure timing properties of sound-evoked activity via the auditory brainstem response (ABR) of α7-nAChR knockout mice of both sexes and wild-type colony controls. We find a significant timing delay in evoked ABR signals that represents midbrain activity in knockouts. We also examine spike-timing properties of neurons in the inferior colliculus, a midbrain nucleus that exhibits high levels of α7-nAChR during development. We find delays of evoked responses along with degraded spiking precision in knockout animals. We find similar timing deficits in responses of neurons in the superior paraolivary nucleus and ventral nucleus of the lateral lemniscus, which are brainstem nuclei thought to shape temporal precision in the midbrain. In addition, we find that other measures of temporal acuity including forward masking and gap detection are impaired for knockout animals. We conclude that altered temporal processing at the level of the brainstem in α7-nAChR-deficient mice may contribute to degraded spike timing in the midbrain, which may underlie the observed timing delay in the ABR signals. Our findings are consistent with a role for the α7-nAChR in types of neurodevelopmental and auditory processing disorders and we identify potential neural targets for intervention.

NEW & NOTEWORTHY Disrupted signaling via the α7-nicotinic acetylcholine receptor (α7-nAChR) is associated with neurodevelopmental disorders that include impaired auditory processing. The underlying causes of dysfunction are not known but a common feature is abnormal timing of neural activity. We examined temporal processing of α7-nAChR knockout mice and wild-type controls. We found degraded spike timing of neurons in knockout animals, which manifests at the level of the auditory brainstem and midbrain.
Impact of traumatic brain injury on amyotrophic lateral sclerosis: from bedside to bench
Authors: Franz Colin K. , Joshi Divya , Daley Elizabeth L. , Grant Rogan A. , Dalamagkas Kyriakos , Leung Audrey , Finan John D. , Kiskinis Evangelos
Published: May 2019

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of upper and lower motor neurons, which manifests clinically as progressive weakness. Although several epidemiological studies have found an association between traumatic brain injury (TBI) and ALS, there is not a consensus on whether TBI is an ALS risk factor. It may be that it can cause ALS in a subset of susceptible patients, based on a history of repetitive mild TBI and genetic predisposition. This cannot be determined based on clinical observational studies alone. Better preclinical models are necessary to evaluate the effects of TBI on ALS onset and progression. To date, only a small number of preclinical studies have been performed, mainly in the superoxide dismutase 1 transgenic rodents, which, taken together, have mixed results and notable methodological limitations. The more recent incorporation of additional animal models such as Drosophila flies, as well as patient-induced pluripotent stem cell-derived neurons, should facilitate a better understanding of a potential functional interaction between TBI and ALS.
Quantification of the Disturbances of Phosphate Series Using the Box-Counting Method on Geoelectrical Images (Sidi Chennane, Morocco)
Authors: Ayad Abderrahim , Amrani Mahacine , Bakkali Saad
Published: May 2019

The phosphate series of Sidi Chennane (Morocco) is frequently affected by sterile bodies called “disturbances” causing many problems during the mining operation. The quantification of these bodies is thus considered as a crucial step for the OCP mining engineers. In following this research, we propose the fractal dimension as a new and simple efficient tool to analyze the disturbed areas. The work was carried out on geoelectrical maps of a study area of 50 hectares located in the northern part of the Sidi Chennane deposit. Fractal dimension was used as a representative parameter for examining the disturbed areas by using the box-counting method. The end result shows a strong linkage between the rate of the disturbances and the corresponding fractal dimension. This may have an important implication to quantify the disturbances and get a precise phosphate reserves estimate.
Galanin Protects Rat Cortical Astrocyte from Oxidative Stress: Involvement of GalR2 and pERK1/2 Signal Pathway
Authors: Sun Jing , Xu Shu , Li Hui , Li Liang , Xu Zhi-Qing David
Published: May 2019

The neuropeptide galanin and its receptors have been found to have protective effects on neurons. However, the role of galanin on astrocytes is still unclear. The present study is aimed at investigating the effects of galanin on the viability of cultured rat cortical astrocytes after oxidative stress induced by H2O2 and possible receptor and signaling mechanisms involved. Treatment of galanin had significant protective effects against H2O2-induced toxicity in the cultured cortical astrocytes. H2O2 induced an upregulation of phosphorylated extracellular signal-related kinase1/2 (pERK1/2) in astrocytes, which was suppressed by coapplication of galanin, suggesting an involvement of the pERK1/2 signal pathway in the protective effects of galanin. GalR2 has higher expression levels than GalR1 and GalR3 in the cultured cortical astrocytes, and GalR2 agonist AR-M1896 mimicked galanin effects on the astrocytes, implying that galanin protective effects mainly mediated by GalR2. Meanwhile, galanin had no effect on the A1-type transformation of rat cortical astrocytes. All those results suggest that galanin protects rat cortical astrocytes from oxidative stress by suppressing H2O2-induced upregulation of pERK1/2, mainly through GalR2.
Preventive Effect of Small-Leaved Kuding Tea (Ligustrum robustum (Roxb.) Bl.) Polyphenols on D-Galactose-Induced Oxidative Stress and Aging in Mice
Authors: Liu Bihui , Ma Ruidong , Zhang Jing , Sun Peng , Yi Ruokun , Zhao Xin
Published: May 2019

Small-leaved Kuding tea is a traditional Chinese tea that is rich in polyphenols. In the current study, we investigated the preventive effect of small-leaved Kuding tea (SLKDT) on D-galactose-induced oxidative aging in mice. Changes in serum, skin, liver, and spleen of experimental animals were determined using biochemical and molecular biology techniques. Biochemical analysis demonstrated that polyphenol extract of SLKDT (PSLKDT) improved the indices of the thymus, brain, heart, liver, spleen, and kidney function in model mice. PSLKDT prevented a decrease in the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH) as well as an increase in nitric oxide (NO) and malondialdehyde (MDA) levels in serum, liver, and spleen. Pathological assessment also showed that PSLKDT reduced oxidative damage induced by D-galactose in skin, liver, and spleen. We further found that PSLKDT upregulated neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), Cu/Zn-SOD, Mn-SOD, catalase (CAT), heme oxygenase-1 (HO-1), nuclear factor (nuclear factor-erythroid 2 related factor 2 (Nrf2), γ-glutamylcysteine synthetase (γ-GCS), and NAD(P)H dehydrogenase [quinone] 1 (NQO1) mRNA expression and downregulated inducible nitric oxide synthase (iNOS) mRNA expression. Protein levels of SOD1 (Cu/Zn-SOD), SOD2 (Mn-SOD), CAT, GSH1 (γ-glutamate-cysteine ligase), and GSH2 (glutathione synthetase) in the liver and spleen were also increased by PSLKDT treatment. Collectively, these results indicate that PSLKDT is effective in preventing D-galactose-induced oxidative aging in mice, and its efficacy is significantly higher than antioxidant vitamin C. Because PSLKDT is a potent antioxidant and antiaging polyphenol, Kuding tea rich in PSLKDT should be considered an ideal drink with antioxidative and antiaging effects.
Nutrient Sensing and Redox Balance: GCN2 as a New Integrator in Aging
Authors: Falcón Paulina , Escandón Marcela , Brito Álvaro , Matus Soledad
Published: May 2019

Aging is a complex process in which the accumulation of molecular, cellular, and organism dysfunction increases the probability of death. Several pieces of evidence have revealed a contribution of stress responses in aging and in aging-related diseases, in particular, the key role of signaling pathways associated to nutritional stress. Here, we review the possible interplay between amino acid sensing and redox balance maintenance mediated by the nutritional sensor general control nonderepressive 2 (GCN2). We discuss this new dimension of nutritional stress sensing consequences, standing out GCN2 as a central coordinator of key cellular processes that assure healthy homeostasis in the cell, raising GCN2 as a novel interesting target, that when activated, could imply pleiotropic benefits, particularly GCN2 intervention and its new unexplored therapeutic role as a player in the aging process.
The Effects of Various Essential Oils on Epilepsy and Acute Seizure: A Systematic Review
Authors: Bahr Tyler A. , Rodriguez Damian , Beaumont Cody , Allred Kathryn
Published: May 2019

Many essential oils (EOs) have anticonvulsant activity and might benefit people with epilepsy. Lemongrass, lavender, clove, dill, and other EOs containing constituents such as asarone, carvone, citral, eugenol, or linalool are good candidates for evaluation as antiepileptic drugs. On the other hand, some EOs have convulsant effects and may trigger seizures in both epileptic and healthy individuals. Internal use of EOs like sage, hyssop, rosemary, camphor, pennyroyal, eucalyptus, cedar, thuja, and fennel can cause epileptic seizures because they contain thujone, 1,8-cineole, camphor, or pinocamphone, which have been identified as convulsive agents. While more research is needed to confirm their mechanisms of action, it appears that the convulsant or anticonvulsant properties of essential oils are largely due to (1) their ability to modulate the GABAergic system of neurotransmission and (2) their capacity to alter ionic currents through ion channels. This review presents a systematic analysis of the current research on EOs and epilepsy, including human case studies, animal models, andin vitrostudies.
MHY2233 Attenuates Replicative Cellular Senescence in Human Endothelial Progenitor Cells via SIRT1 Signaling
Authors: Lamichane Shreekrishna , Baek Sang Hong , Kim Yeon-Ju , Park Ji Hye , Dahal Lamichane Babita , Jang Woong Bi , Ji SeungTaek , Lee Na Kyung , Dehua Li , Kim Da Yeon , Kang Songhwa , Seong Ha Jong , Yun Jisoo , Lee Dong Hyung , Moon Hyung Ryong , Chung Hae Young , Kwon Sang-Mo
Published: May 2019

Cardiovascular diseases (CVDs) are a major cause of death worldwide. Due to the prevalence of many side effects and incomplete recovery from pharmacotherapies, stem cell therapy is being targeted for the treatment of CVDs. Among the different types of stem cells, endothelial progenitor cells (EPCs) have great potential. However, cellular replicative senescence decreases the proliferation, migration, and overall function of EPCs. Sirtuin 1 (SIRT1) has been mainly studied in the mammalian aging process. MHY2233 is a potent synthetic SIRT1 activator and a novel antiaging compound. We found that MHY2233 increased the expression of SIRT1, and its deacetylase activity thereby decreased expression of the cellular senescence biomarkers, p53, p16, and p21. In addition, MHY2233 decreased senescence-associated beta-galactosidase- (SA-β-gal-) positive cells and senescence-associated secretory phenotypes (SASPs), such as the secretion of interleukin- (IL-) 6, IL-8, IL-1α, and IL-1β. MHY2233 treatment protected senescent EPCs from oxidative stress by decreasing cellular reactive oxygen species (ROS) levels, thus enhancing cell survival and function. The angiogenesis, proliferation, and migration of senescent EPCs were enhanced by MHY2233 treatment. Thus, MHY2233 reduces replicative and oxidative stress-induced senescence in EPCs. Therefore, this novel antiaging compound MHY2233 might be considered a potent therapeutic agent for the treatment of age-associated CVDs.
Normotensive, Oversized Pheochromocytoma in Twin-Pregnancy: Analysis of Therapeutic Challenges in a Rare Case
Authors: Özveren Bora , Ulugöl Halim , Türkeri Levent
Published: May 2019

An asymptomatic, normotensive 36-year-old woman in the second trimester of a twin-gestation was diagnosed with a 11 cm adrenal pheochromocytoma. Considering the hemodynamic stability of the patient, tumor size, and gestational age, the therapeutic decision of a multidisciplinary team ensued open surgical excision without any preoperative antihypertensive preparation. Following successful removal of pheochromocytoma, the patient had a normal subsequent course of pregnancy and cesarean section delivery of healthy twins at term. This unique case of a normotensive, incidental, large-sized pheochromocytoma in a twin-pregnancy illustrates that the decisions of management in such a rare occurrence should be based on individual features of the patient. Our experience supports that α-adrenergic blockade may not be essential in normotensive pheochromocytoma in pregnancy and open-surgery remains as a safe approach in the management of large adrenal tumors in twin-pregnant patients following a multidisciplinary consultation.
Quality Prediction Model Based on Novel Elman Neural Network Ensemble
Authors: Xu Lan , Zhang Yuting
Published: May 2019

In this paper, we propose a novel prediction algorithm based on an improved Elman neural network (NN) ensemble for quality prediction, thus achieving the quality control of designed products at the product design stage. First, the Elman NN parameters are optimized using the grasshopper optimization (GRO) method, and then the weighted average method is improved to combine the outputs of the individual NNs, where the weights are determined by the training errors. Simulations were conducted to compare the proposed method with other NN methods and evaluate its performance. The results demonstrated that the proposed algorithm for quality prediction obtained better accuracy than other NN methods. In this paper, we propose a novel Elman NN ensemble model for quality prediction during product design. Elman NN is combined with GRO to yield an optimized Elman network ensemble model with high generalization ability and prediction accuracy.
The Impact of Dysarthria on Laypersons’ Attitudes towards Adults with Cerebral Palsy
Authors: Schölderle Theresa , Staiger Anja , Schumacher Barbara , Ziegler Wolfram
Published: May 2019

Objective: This study investigated laypersons’ attitudes towards adults with dysarthria due to cerebral palsy (CP). We aimed to explore the impact of the overall severity and of specific symptoms of dysarthria on laypersons’ evaluations. Patients and Methods: Eighteen adults with dysarthria due to CP and 6 nondysarthric controls participated as speakers. The individuals with CP underwent dysarthria assessment based on a standardized tool. The results were compared to those of a listening experiment with 20 laypersons. A text passage spoken by all speakers was presented to the listeners, who provided their evaluations using rating scales specifically developed for this study. The tool addressed 3 dimensions of attitudes: (1) estimation of a speaker’s cognitive-linguistic abilities; (2) attribution of personality and social characteristics, and (3) listeners’ emotions and behavioral tendencies towards the speaker. Results: Severity of dysarthria was strongly correlated with the overall attitudes. Regression analyses identified different symptoms as predictors of the listeners’ judgements. Conclusion: Severity of dysarthria seems to have a major impact on laypersons’ attitudes. Results suggest that speech symptoms may have a very specific influence on laypersons’ evaluations. This may be important for clinical care, since symptoms with the most negative impact should be focused on in treatment.
Connected and Automated Vehicles: Chances for Elderly Travellers
Authors: Millonig Alexandra
Published: May 2019

Connected and automated vehicles (CAV) are expected to improve the mobility of older people by compensating for the effects of a decreasing age-related fitness to drive. However, the technology is still under development and it is unclear how automated transport services will be implemented and which effects will be achievable. This paper aims to assess the potential of connected and automated transport to improve the mobility of older people. The discussion focuses on potentially disrupting highly automated services; in addition, general effects on the transport system and quality of life influenced by the increased mobility of older people are considered. Based on findings from mobility behavior research and studies exploring the mobility barriers of older people, the current mobility gaps are systematically analyzed on external barriers (availability of transport and related information) and 3 different internal barrier levels: access (physical limitations), ability (skills and know-how), and acceptance (experiences and symbolic meaning associated with a service). Subsequently, the potential of CAV to bridge these gaps is assessed. The results show that CAV can mitigate several of the barriers experienced by older people, especially barriers related to motor, sensory, and cognitive limitations. For other gaps, such as socioeconomic, usability, or acceptance issues, the potential benefits strongly depend on the way CAV are implemented and how the transformation takes place. Additionally, improvement of the mobility of older people by car can also have negative effects on their health and well-being, as physical activities like walking and social relations like receiving support from others may decline. In general, the introduction of CAV shows significant potential to improve the mobility of elderly travelers. However, the role automated services will take over in the future transport system can also bear some risks, especially if automated cars are used excessively. A comprehensive design of future transport systems is required to define the role of automated services in order to target the current supply gaps and improve the quality of life of transport-disadvantaged groups while avoiding unduly traffic growth.
Applicability of Resonance Tube Phonation in Water for Semi-Occluded Vocal Tract Voice Training and Therapy
Authors: Sanz López Lorena , Pérez Marrero Natasha , Rivera Rodriguez Teresa
Published: May 2019

Background: Exercises involving tube phonation in water (TPW) have emerged as an alternative to conventional voice therapy techniques. The objective was to determine whether the results of these techniques were comparable to each other for the treatment of voice pathology, as well as to compare the costs implicated in the delivery of each treatment. Methods: A retrospective, descriptive, and observational study was performed that included all patients evaluated in our voice unit in 2015 who received vocal rehabilitation treatments. They were divided into two groups depending on the treatment technique used. The patients’ voice was evaluated subjectively using the GRBAS scale. We compared the clinical results and the specific costs of each technique. Results: A total of 55 patients were studied, of which 28 followed TPW exercises, and 27 underwent supervised vocal rehabilitation (SVR). Most of the patients who received TPW therapy were diagnosed with functional dysphonia, whereas functional-organic dysphonia was the most common pathology in the SVR group. Significant differences were evident when the total GRBAS scores were compared before and after the treatments, yet not when the GRBAS scores were compared between the two rehabilitation techniques. The incremental cost-effectiveness analysis revealed that TPW was less expensive than SVR, with both techniques proving to be equally effective in improving the pathological problems. Conclusions: TPW is similarly effective as SVR techniques in treating voice pathologies, yet it is significantly cheaper in terms of healthcare costs.
Is the Real Prevalence of Pancreatic Neuroendocrine Tumors Underestimated? A Retrospective Study on a Large Series of Pancreatic Specimens
Authors: Partelli Stefano , Giannone Fabio , Schiavo Lena Marco , Muffatti Francesca , Andreasi Valentina , Crippa Stefano , Tamburrino Domenico , Zamboni Giuseppe , Rubini Corrado , Doglioni Claudio , Falconi Massimo
Published: May 2019

Background/Aims: The annual incidence of pancreatic neuroendocrine tumors (PanNET) has been estimated to be around 0.8/100,000 inhabitants. The aim of this study was to determine the frequency of incidental histological diagnosis of PanNET in pancreatic specimen evaluation for a purpose other other than PanNET diagnosis. Methods: One thousand seventy-four histopathological examinations of pancreatic specimens performed in 3 centers in Italy were retrospectively reviewed. All cases with a main pathological diagnosis of PanNET were excluded. Results: An incidental associated diagnosis of PanNET was made in 41 specimens (4%). Among those 41 cases, 29 (71%) had a largest diameter <5 mm (microadenoma), whereas the other 12 (29%) had a maximum size ≥5 mm (median diameter of the whole series = 3 mm, range 1–15). The association with a main diagnosis of intraductal papillary mucinous neoplasms (IPMN) was significantly higher for patients who had an incidental PanNET (p = 0.048). There was no association between incidental diagnosis of PanNET and age, gender, BMI, smoking habit, diabetes, and type of operation. Conclusions: The frequency of incidental histological diagnosis of PanNET is considerably high, suggesting that their real prevalence is probably underestimated. The present study suggests a possible correlation between the incidental occurrence of PanNET and IPMN.
Evaluation of Small-Bowel Patency in Crohn’s Disease: Prospective Study with a Patency Capsule and Computed Tomography
Authors: Silva Marco , Cardoso Hélder , Cunha Rui , Peixoto Armando , Gaspar Rui , Gomes Sara , Santos Ana Luísa , Lopes Susana , Macedo Guilherme
Published: May 2019

Background and Purpose: Patency capsule (PC) examination is usually performed – previously to capsule endoscopy – to evaluate small-bowel patency in patients with established Crohn’s disease (CD). The reported PC retention rate is significantly higher than expected. Our aims were to assess small-bowel patency, to determine the precise location of the retained PC in patients with CD, and to determine the false positive rate of evaluation with a radiofrequency identification tag (RFIT) scanner. Methods: This is a prospective single-center study including CD patients with clinical indication for small-bowel capsule endoscopy. PillCam® PC examination was performed on all patients to assess small-bowel patency. On all patients with a positive identification of the PC using an RFIT scanner, 30 h after ingestion, an abdominal CT was performed in order to identify its precise location. Results: Fifty-four patients were included. The PC retention rate, according to evaluation with the RFIT scanner, was 20% (in 11 patients) 30 h after ingestion. These patients were then submitted to abdominal CT, which revealed that there was small-bowel retention in 5 cases (9%). Higher CRP levels, penetrating disease, and a history of abdominal surgery were associated with an increased risk of PC retention (p = 0.007, p = 0.011, and p = 0.033, respectively). On multivariate analysis, there was an independent association between small-bowel PC retention and CRP levels >5 mg/dL (OR = 15.5; p = 0.03). Discussion: The small-bowel PC retention rate (9%) was considerably lower than those found in previous reports. Our results show that, with this protocol, the false-positive cases of RFIT scans or plain abdominal X-rays may be avoided. This may contribute to more extensive application of capsule endoscopy without the risk of small-bowel retention.
Assessment of Prenatal Kynurenine Metabolism Using Tissue Slices: Focus on the Neosynthesis of Kynurenic Acid in Mice
Authors: Notarangelo Francesca M. , Beggiato Sarah , Schwarcz Robert
Published: May 2019

Several lines of evidence support the hypothesis that abnormally elevated brain levels of kynurenic acid (KYNA), a metabolite of the kynurenine pathway (KP) of tryptophan degradation, play a pathophysiologically significant role in schizophrenia and other major neurodevelopmental disorders. Studies in experimental animal models suggest that KP impairments in these diseases may originate already in utero since prenatal administration of KYNA’s bioprecursor, kynurenine, leads to biochemical and structural abnormalities as well as distinct cognitive impairments in adulthood. As KP metabolism during pregnancy is still insufficiently understood, we designed this study to examine the de novo synthesis of KYNA and 3-hydroxykynurenine (3-HK), an alternative biologically active product of kynurenine degradation, in tissue slices obtained from pregnant mice on gestational day (GD) 18. Fetal brain and liver, placenta, and maternal brain and liver were collected, and the tissues were incubated in vitroin the absence or presence of micromolar concentrations of kynurenine. KYNA and 3-HK were measured in the extracellular milieu. Basal and newly produced KYNA was detected in all cases. As KYNA formation exceeded 3-HK production by 2–3 orders of magnitude in the placenta and maternal brain, and as very little 3-HK neosynthesis was detectable in fetal brain tissue, detailed follow-up experiments focused on KYNA only. The fetal brain produced 3–4 times more KYNA than the maternal brain and placenta, though less than the maternal and fetal liver. No significant differences were observed when using tissues obtained on GD 14 and GD 18. Pharmacological inhibition of KYNA’s main biosynthetic enzymes, kynurenine aminotransferase (KAT) I and KAT II, revealed qualitative and quantitative differences between the tissues, with a preferential role of KAT I in the fetal and maternal brain and of KAT II in the fetal and maternal liver. Findings using tissue slices from KAT II knockout mice confirmed these conclusions. Together, these results clarify the dynamics of KP metabolism during pregnancy and provide the basis for the conceptualization of interventions aimed at manipulating cerebral KP function in the prenatal period.
Can Oral Fesoterodine Be an Alternative for Intravesical Oxybutynin Instillations in Children with Neuropathic Bladder Dysfunction?
Authors: van den Heijkant Marleen , De Coster Katrien , Jansen Katrien , Bogaert Guy
Published: May 2019

Purpose: A low-pressure bladder in children with neuropathic bladder dysfunction can be achieved using anticholinergic medication. Due to the significant side effects of oral oxybutynin, our patients are treated with daily intravesical oxybutynin instillations. Newer oral anticholinergic medication, such as fesoterodine, claim to have fewer side effects in a once daily formulation. Because once-daily oral intake is easier than performing twice-daily intravesical instillations, we studied the effects of switching from intravesical oxybutynin to oral fesoterodine and compared the clinical response, urodynamic parameters and side effects. Patients and Methods: Twenty children (11 girls, 9 boys, 4–17 years) with neuropathic bladder dysfunction who perform clean intermittent catheterization and use intravesical oxybutynin instillations twice daily were included in this prospective study. Voiding diaries, a behavioural checklist, urodynamic investigations, vital signs and blood samples were evaluated at baseline during treatment with intravesical oxybutynin and repeated after 40 days of oral fesoterodine. Results: Out of 20, 13 (65%) children showed an identical objective dryness (pad-test), 2 (10%) improved and 5 (25%) got worse. Seven (35%) children reported equal dryness, 7 (35%) reported improvement and 6 (30%) reported that it got worse. From a urodynamic perspective, 13 (65%) children remained identical, 3 (15%) improved and 4 (20%) got worse. Four (20%) children reported a light to moderate dry mouth, 1 (5%) a headache, 1 (5%) behavioural changes during fesoterodine administration, 1 (5%) an increased appetite, 1 (5%) nausea and 1 (5%) hot flushes. Conclusions: The urodynamics after 40 days of fesoterodine were in 16 (80%) identical or better and could be a safe alternative for oxybutynin instillations in children with neuropathic bladder dysfunction.
Lifestyle Interventions for Weight Control Modified by Genetic Variation: A Review of the Evidence
Authors: Tan Pui Yee , Mitra Soma Roy , Amini Farahnaz
Published: May 2019

Background/Aims: Excess weight gain is a result of the interaction between diet, environment, and genes. Evidence suggests that responses to lifestyle interventions to manage weight are partially modified by genetic factors. This review is aimed at summarizing the current evidence from studies done on gene variants – single nucleotide polymorphisms (SNPs) – and intervention outcomes on weight loss and obesity-related traits. Methods: Intervention studies published in English between 2000 and August 2018 were retrieved from PubMed, Google Scholar, and Web of Science using various keywords. Results: This article is a review of 36 studies conducted in 13 different countries which included a total of 15,931 participants between 19 and 70 years of age. The effect of 26 genes and 64 SNPs on the reduction of body weight and metabolic risk factors in response to diet, exercise, and lifestyle interventions was reviewed. Conclusion: Gene-lifestyle interaction studies on the same candidate gene in different populations have reported information which is challenging to interpret. Thus, it is difficult to arrive at a particular model for a strategy on weight management at this point in time. Most of the intervention studies focus on the effect of variants of a single candidate gene on weight loss. Further evidence from large-scale studies is necessary to assess the effect of multiple candidate genes to compute a gene score that could be used in a model intervention programme. Our review suggests that a healthy lifestyle with a balanced diet and regular physical activity will benefit individuals who carry the risk alleles of the obesity-related candidate genes. This message should be the mainstay of the recommendations and guidelines published by nutrition societies across the world.
A Retrospective Study on Efficacy and Safety of Rivaroxaban and Dalteparin for Long-Term Treatment of Venous Thromboembolism in Patients with Lung Cancer
Authors: Lee Jang Ho , Hyun Dong-gon , Choi Chang Min , Lee Jae Cheol , Kim Woo Sung , Oh Yeon-Mok , Lee Sang-Do , Lee Jae Seung
Published: May 2019

Background: Standard therapy for cancer-associated venous thromboembolism (VTE) is low-molecular-weight heparin. The use of direct oral anticoagulants for cancer-associated VTE has increased; however, their efficacy and safety in lung cancer patients remain unclear. Objectives: We examined the efficacy and safety of rivaroxaban compared with dalteparin for cancer-associated VTE in patients with primary lung cancer. Methods: A single-center retrospective study of 204 patients with primary lung cancer who were prescribed rivaroxaban (n = 131) or dalteparin (n = 73) for VTE was performed. The primary endpoint was a composite event including recurrence and major or clinically relevant nonmajor bleeding. Secondary endpoints included the incidence of recurrence, major and clinically relevant nonmajor bleeding, all-cause mortality, and bleeding or pulmonary embolism-related mortality. Results: The composite event occurred in 38 (29.0) and 12 (16.4%) patients in the rivaroxaban and dalteparin (p = 0.045) groups, respectively. The multivariate Cox proportional hazards model for age, Eastern Cooperative Oncology Group performance score, and bleeding risk factors revealed the rivaroxaban group showed a 1.176-fold composite event risk without statistical significance (0.595–2.324, p = 0.641). There was no statistically significant intergroup difference for the incidence of VTE recurrence (5.3% in the rivaroxaban group versus 2.7% in the dalteparin group, p = 0.495) and major or clinically relevant nonmajor bleeding (23.7% in the rivaroxaban group versus 13.7% in the dalteparin group, p = 0.089). There was no significant difference in the all-cause mortality rate (hazard ratio 0.864, 95% CI 0.624–1.196, p = 0.337). Conclusions: There was no difference in the safety and efficacy profile of rivaroxaban compared with dalteparin. Therefore, rivaroxaban may be a valuable treatment option for lung cancer-associated VTE.