bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma Lipoprotein(a) Levels and Atherosclerotic Renal Artery Stenosis in Hypertensive Patients
Authors: Catena Cristiana , Colussi GianLuca , Nait Francesca , Capobianco Frine , Sechi Leonardo A
Published: June 2015

Background/Aims: The contribution of emergent cardiovascular risk factors to atherosclerotic renal artery stenosis (ARAS) is debated. We investigated the relationship of lipoprotein(a) and prothrombotic factors with ARAS in hypertension. Methods: In 50 hypertensive patients with angiographic evidence of ARAS and 58 hypertensive patients who had comparable cardiovascular risk factor burden but no evidence of renovascular disease, we measured renal function, lipoprotein(a), homocysteine, and hemostatic-fibrinolytic markers. Results: Patients with ARAS were more frequently smokers and had longer duration of hypertension, heavier antihypertensive treatment, and worse renal function than controls. Lipoprotein(a) was higher in patients with ARAS than controls, whereas no differences were found in homocysteine and all hemostatic variables. Multivariate analysis showed that lipoprotein(a) was associated with ARAS independent of other confounders including renal function and history of coronary heart, cerebrovascular, and peripheral artery disease. Conclusion: Lipoprotein(a) might contribute to the development of ARAS and detection of elevated levels of this lipoprotein could raise the suspicion of renovascular disease in patients with high blood pressure.
Cost-Effectiveness of Partially Hydrolyzed Whey Protein Formula in the Primary Prevention of Atopic Dermatitis in High-Risk Urban Infants in Southeast Asia
Authors: Botteman Marc , Detzel Patrick
Published: June 2015

Background: Atopic dermatitis (AD) is one of the most common skin conditions among infants. Proteins found in cow's milk formula (CMF) have been found to be attributable to heightened AD risk, particularly in infants with familial AD heredity. Previous studies have suggested that intervention with partially hydrolyzed formula in nonexclusively breastfed infants can have a protective effect against AD development. Objective: The aim of the present study was to compare the estimates of the economic impact of reducing the AD incidence by feeding a partially hydrolyzed whey-based formula (PHF-W) instead of a standard CMF to high-risk nonexclusively breastfed urban infants for the first 17 weeks of life in the Philippines, Malaysia, and Singapore. Methods: In each country, a mathematical model simulated AD incidence and burden from birth to 6 years of age of using PHF-W versus CMF in the target population using data from the German Infant Nutritional Intervention study. The models integrated literature, current cost and market data, and expert clinician opinion. Modeled outcomes included AD risk reduction, time spent after AD diagnosis, AD symptom-free days, quality-adjusted life years (QALYs), and costs (direct and indirect). Outcomes were discounted at 3% per year. Costs were expressed in USD. Results: Feeding high-risk infants PHF-W instead of CMF resulted in an estimated absolute 14% (95% CI 1-24) AD risk reduction, a 0.69-year (95% CI 0.25-1.13) reduction in the time spent after AD diagnosis per child, reductions of 16-38 AD days, and gains in 0.02-0.04 QALYs, depending on the country. The per-child AD-related 6-year cost-saving estimates of feeding high-risk infants with PHF-W versus CMF were USD 739 in Singapore, USD 372 in Malaysia, and USD 237 in the Philippines.
The Optimal Treatment Modality in Patients with T4N2M0 Non-Small Cell Lung Cancer: The Best Choice May Be Definitive Chemoradiotherapy Followed by Consolidation Chemotherapy
Authors: Mutlu Hasan , Arslan Deniz , Gündüz Şeyda , Tural Deniz , Büyükçelik Abdullah , Benderli Cihan Yasemin , Aslan Tuncay , Bozcuk Hakan , Şenol Coşkun Hasan
Published: June 2015

Background: Stage IIIB non-small cell lung cancer (NSCLC) consists of T4N2M0 and TXN3M0 NSCLC. In the present study, we aimed to evaluate the efficacy of different treatment strategies on the survival of patients with radiologically confirmed T4N2M0 NSCLC. Methods: A total of 145 patients were evaluated in three groups according to the treatment protocol: induction chemotherapy followed by chemoradiotherapy (induction group); chemoradiotherapy (CRT group), and chemoradiotherapy followed by consolidation chemotherapy (consolidation group). The groups were compared regarding survival. Results: The median progression-free survival (PFS) was 10.9, 10.8 and 17.1 months for the induction, CRT and consolidation groups, respectively (p = 0.021). The median overall survival (OS) was 17.6, 13.8 and 25.2 months for the induction, CRT and consolidation groups, respectively (p = 0.001). Conclusions: The patients with T4N2M0 NSCLC who were treated with chemoradiotherapy followed by consolidation chemotherapy had the best outcome in terms of PFS and OS.
Differences in Physicians' and Patients' Perception of Acute Hypothyroid Symptoms Induced by Thyroid Hormone Withdrawal in Thyroid Cancer Patients: A Multicenter Survey in Korea
Authors: Lim Dong Jun , Kim Won Bae , Kim Bo Hyun , Kim Tae Yong , Jo Young Suk , Kang Ho-Cheol , Park Young Joo , Yi Ka Hee , Shong Minho , Kim In Joo , Park Do Joon , Kim Sun Wook , Chung Jae Hoon , Lee Jaetae , Koong Sung-Soo , Shong Young Kee
Published: June 2015

Background: Acute short-term hypothyroidism induced by thyroid hormone withdrawal (THW) for follow-up surveillance or therapeutic radioiodine causes patients with differentiated thyroid cancer to suffer from a myriad of deleterious symptoms. Objectives: To know how patient recognition of hypothyroid symptoms compares to physician perception of patient symptoms. Methods: The survey was performed in 10 referral hospitals throughout Korea from December 2010 to May 2011 and targeted patients with total thyroidectomy and remnant ablation. The survey consisted of questions regarding the effect of THW on patient symptoms, the duration of symptoms, impact on social life, and patient complaints. The physicians treating thyroid cancer patients also responded to the survey and provided their perceptions of patient symptoms and treatment decisions. Results: About 70% of the patients responded that they experienced a negative physical or psychological impact on their life and work due to hypothyroid symptoms. However, 76% of doctors thought hypothyroidism could negatively impact a patient's daily life but would be endurable. Two thirds of physicians do not routinely recommend recombinant human TSH (rhTSH) to their patients. Multivariate analysis showed patients with female sex, stronger educational background, emotionally negative experiences of hypothyroidism, and younger age were more willing to pay for therapy that could prevent hypothyroidism symptoms. Conclusions: There was a substantial gap in the perception of hypothyroid symptoms during THW between physicians and patients. Physicians who are aware of the seriousness of hypothyroidism in their patients were more likely to recommend the use of rhTSH for their patients.
Studying Cognition through Time in a Classroom Community: The Interplay between “Everyday” and “Scientific Concepts”
Authors: Saxe Geoffrey B. , de Kirby Kenton , Kang Bona , Le Marie , Schneider Alyse
Published: June 2015

This paper presents an analytic approach for understanding the interplay through time between “scientific” and “everyday concepts” in a mathematics classroom community. To illustrate the approach, we focus on an elementary classroom implementing an integers and fractions lesson sequence that makes use of the number line as a principal representational context. In our analysis of the community's emerging collective practices (recurring structures of joint activity), we trace the interplay between children's sensorimotor actions (displacing, counting, and splitting) and the mathematical definitions supported in the classroom, like definitions of unit interval or equivalent fractions. In our illustrative analysis, we find that the teacher orchestrated collective practices to support the use of actions to make sense of the formal definitions, and the use of definitions to regulate actions. Though we illustrate the analytic approach for a particular classroom community, the approach illuminates teaching-learning dynamics that transcend any particular classroom or subject matter domain.
ATP8B1 and ATP11C: Two Lipid Flippases Important for Hepatocyte Function
Authors: Naik Jyoti , de Waart Dirk R. , Utsunomiya Karina , Duijst Suzanne , Mok Kam Ho , Oude Elferink Ronald P.J. , Bosma Piter J. , Paulusma Coen C.
Published: June 2015

P4 ATPases are lipid flippases and transport phospholipids from the exoplasmic to the cytosolic leaflet of biological membranes. Lipid flipping is important for the biogenesis of transport vesicles. Recently it was shown that loss of the P4 ATPases ATP8B1 and ATP11C are associated with severe Cholestatic liver disease. Mutation of ATP8B1 cause progressive familial Intrahepatic Cholestasis type 1 (PFIC1)and benign recurrent intrahepatic cholestasis type 1 (BRIC 1). From our observations we hypothesized that ATP8B1 deficiency causes a phospholipids randomization at the canalicular membrane, which results in extraction of cholesterol due to increase sensitivity of the canalicular membrane. Deficiency of ATP11C causes conjugated hyperbilirubinemia. In our preliminary result we observed accumulation of unconjugated bile salts in Atp11c deficient mice probably because of regulation in the expression or function of OATP1B2. Similar to ATP8B1, ATP11C have regulation on membrane transporters.
Interactions between Diet, Bile Acid Metabolism, Gut Microbiota, and Inflammatory Bowel Diseases
Authors: Devkota Suzanne , Chang Eugene B.
Published: June 2015

The composite human gut microbiomes of Western populations have changed over the past century, brought on by new environmental triggers that often have a negative impact on human health. Diets high in saturated fats and refined sugars and low in fiber are leading candidates for these events and for triggering the increased prevalence of immune-mediated diseases like inflammatory bowel disease (IBD). Our studies have shown that consumption of a ‘Western' diet high in saturated (milk-derived) fat (MF) or n-6 polyunsaturated (safflower oil) fat have similar effects on the structure of the colonic microbiome of wild-type and IL- 10-/- mice, characterized by increased Bacteroidetes and decreased Firmicutes. However, the MF diet uniquely promotes the expansion of an immunogenic sulfite-reducing pathobiont, Bilophila wadsworthia, a member of the Deltaproteobacteria and minor component of the gut microbiome. This bacterial bloom results from a MF diet-induced shift in hepatic conjugation of bile acids, from glycocholic to taurocholic (TC) acid, which is important for solubilizing the more hydrophobic MF diet. However, it is also responsible for delivery of taurine-derived sulfur to the distal bowel, promoting the assemblage of bile-tolerant microbes such as B. wadsworthia. The bloom of this species promotes a Th1-mediated immune response and the development of colitis in IL-10-/- mice. A similar bloom of B. wadsworthia is seen when IL-10-/- mice are fed a low-fat diet supplemented with TC. B. wadsworthia colonization of monoassociated germ-free IL-10-/- mice was dependent on the host consuming either a high-saturated MF diet or the gavage with TC. Together, these data provide a plausible explanation for the link between diseases such as IBD and dietary-mediated selection of gut microbial pathobionts in genetically susceptible hosts. With this knowledge, it may be possible to mitigate the bloom of these types of pathobionts by modifying the conjugation states of bile acids.
Bile Acid-Induced Cholemic Nephropathy
Authors: Krones Elisabeth , Wagner Martin , Eller Kathrin , Rosenkranz Alexander R. , Trauner Michael , Fickert Peter
Published: June 2015

Kidney injury in deeply jaundiced patients became known as cholemic nephropathy. This umbrella term covers impaired renal function in cholestatic patients with characteristic histomorphological changes including intratubular cast formation and tubular epithelial cell injury. Cholemic nephropathy represents a widely underestimated but important cause of kidney dysfunction in patients with cholestasis and advanced liver disease. However, the nomenclature is inconsistent since there are numerous synonyms used; the underlying mechanisms of cholemic nephropathy are not entirely clear, and widely accepted diagnostic criteria are still missing. Consequently, the current article aims to summarize the present knowledge on the clinical and morphological characteristics, available preclinical models, derived potential pathomechanisms, and future diagnostic and therapeutic strategies in cholemic nephropathy. Furthermore, we provide a potential research agenda for this evolving field.
Universal Definition of Myocardial Infarction: Clinical Insights
Authors: Paiva Luis , Providência Rui , Barra Sérgio , Dinis Paulo , Faustino Ana C. , Gonçalves Lino
Published: June 2015

Aims: The universal definition of myocardial infarction (MI) classifies acute ischaemia into different classes according to lesion mechanism. Our aim was to perform a detailed comparison between these different types of MI in terms of baseline characteristics, management and prognosis. Methods and Results: An observational retrospective single-centre cohort study was performed, including 1,000 consecutive patients admitted for type 1 (76.4%) or type 2 MI (23.6%). Type 2 MI patients were older, had a higher prevalence of comorbidities and worse medical status at admission. In-hospital mortality did not differ significantly between the MI groups (8.8 vs. 9.7%, p = 0.602). However, mortality during follow-up was almost 3 times higher in type 2 MIs (HR 2.75, p < 0.001). Type 2 MI was an independent all-cause mortality risk marker, adding discriminatory power to the GRACE model. Finally, important differences in traditional risk score performances (GRACE, CRUSADE) were found between both MI types. Conclusions: Several important baseline differences were found between these MI types. Regarding prognosis, long-term survival is significantly compromised in type 2 MIs, potentially translating patients' higher medical complexity and frailty. Distinction between type 1 and type 2 MI seems to have important implications in clinical practice and likely also in the results of clinical trials.
Monkeys and Rats Are Not Susceptible to Ferret Hepatitis E Virus Infection
Authors: Li Tian-Cheng , Yoshizaki Sayaka , Ami Yasushi , Suzaki Yuriko , Yang Tingting , Takeda Naokazu , Takaji Wakita
Published: June 2015

Ferret hepatitis E virus (HEV), a novel hepatitis E-like virus, has been identified in ferrets in the Netherlands, Japan, and the US. To determine whether ferret HEV transmits to other animals, we inoculated laboratory rats (Wistar), nude rats (Long-Evans-rnu/rnu), and cynomolgus monkeys with ferret HEV (F4351) by intravenous injection. None of the animals demonstrated a positive sign for virus replication, indicating that rats and monkeys are not susceptible to ferret HEV.
Anti-Fibrotic Effect of Plumbagin on CCl4-Lesioned Rats
Authors: Wei Yanfei , Huang Minkui , Liu Xuemei , Yuan Zhang , Peng Yue , Huang Zhenqing , Duan Xuelin , Zhao Tiejian
Published: June 2015

Background/Aims: Our previous studies have shown that plumbagin effectively inhibits hepatic stellate cell (HSC) proliferation. Thus, plumbagin-mediated anti-fibrotic effects in vivo merit further investigation. Methods: We used rat models to assess the potential benefits of plumbagin against CCl4-induced liver fibrosis. Results: The results showed that plumbagin lowered the serum concentrations of liver functional enzymes (ALT, AST, ALB, TBIL) in CCl4-fibrotic rats while reducing inflammatory cytokine levels (IL-6, TNF-a). As reflected in pathological examinations, rats that were administered plumbagin showed decreased collagen markers (HA, LN, PCIII and CIV) in liver tissues and improved hepatocellular impairments. In addition, plumbagin contributed to down-regulating NF-κB and TLR-4 mRNA in CCl4-lesioned livers. As revealed in the immunohistochemical assay, plumbagin-administered rats showed reduced levels of a-SMA and TNF-a immunoreactive cells in liver tissue. Conclusion: Collectively, these findings offer appealing evidence that plumbagin may serve as an anti-fibrotic medication through inactivating the NF-κB/TLR-4 pathway that is associated with inflammatory reactions, thereby mitigating liver fibrosis.
TGF-β Regulates Hepatocellular Carcinoma Progression by Inducing Treg Cell Polarization
Authors: Shen Yinan , Wei Yongpeng , Wang Zhouchong , Jing Yingying , He Haiguan , Yuan Jianyong , Li Rong , Zhao Qiudong , Wei Lixin , Yang Tian , Lu Junhua
Published: June 2015

Background/Aims: TGF-β plays a key role in the progression of various tumors. The main objective of our study was to investigate whether TGF-β is able to regulate N-nitrosodiethylamine (DEN)-induced hepatocellular carcinoma (HCC) progression in a mouse model by inducing Treg cell polarization. Methods: HCC progression, TGF-β and Foxp3 expression levels, serum TGF-β, IL10 and GP73 levels as well as percentage of Treg cells were analyzed in healthy, HCC and HCC+SM-16 mouse groups. The effect of TGF-β on Treg cell polarization in vitro was measured by flow cytometric analysis. The expression of TGF-β and IL10 was identified by IHC in HCC patients and the correlation between TGF-β and IL10 was also assessed. Results: TGF-β expression is up-regulated in a DEN-induced HCC mouse model. TGF-β can promote the differentiation of Foxp3+CD4+ T cells (Treg cells) in vitro. However, blocking the TGF-β pathway with a specific TGF-β receptor inhibitor, SM-16, reduced HCC progression and the percentage of Treg cells in liver tissue. The correlation between TGF-β and Treg cells was also confirmed in HCC patients and the expression of both TGF-β and IL-10 was shown to be associated with HCC progression. Conclusion: TGF-β is necessary for HCC progression, acting by inducing Treg cell polarization.
Activated Phosphatidylinositol 3-Kinase/Akt Inhibits the Transition of Endothelial Progenitor Cells to Mesenchymal Cells by Regulating the Forkhead Box Subgroup O-3a Signaling
Authors: Zhang Zongqi , Zhang Tiantian , Zhou Yaoyao , Wei Xiaowei , Zhu Jianbing , Zhang Junfeng , Wang Changqian
Published: June 2015

Background and Aims: Endothelial progenitor cells (EPCs) differentiate into mature endothelial cells and may thus be candidates for ischemic disease therapy; however, the transition of EPCs to mesenchymal cells is not fully understood. We explored the role of phosphatidylinositol 3-kinase (PI3K)/Akt signaling in endothelial-to-mesenchymal transition (EndMT) induced by transforming growth factor beta 1 (TGF-β1). Methods: Rat bone marrow-derived EPCs were isolated by using Ficoll-Isopaque Plus density-gradient centrifugation. EndMT was induced by TGF-β1 (5 ng/mL). PI3K/Akt signaling was activated by IGF-1 or Lenti-PIK3R2 shRNA. Additionally, FoxO3a expression was suppressed by a lentiviral vector (Lenti-FoxO3a shRNA). Smad3 and FoxO3a co-localization was detected by confocal immunofluorescence microscopy. The expressions of molecules involved in EndMT were exmined by using Western-blot analysis. Results: EndMT of EPCs was fully developed after TGF-β1 treatment (5 ng/mL) for 7 days. PIK3R2 expression in EPCs was driven by TGF-β1. Lenti-PIK3R2 shRNA blocked alpha-smooth muscle actin (α-SMA) expression in EPCs treated with TGF-β1, drove PI3K/Akt activation, and increased expression of phosphorylated FoxO3a instead of phosphorylated Smad3. The effect of Lenti-PIK3R2 shRNA was reduced by LY294002, a specific inhibitor of PI3K. IGF-1 attenuated α-SMA protein expression in EPCs treated with TGF-β1. Similar to Lenti-PIK3R2 shRNA, IGF-1 also inhibited and elevated the phosphorylation of Smad3 and FoxO3a, respectively. IGF-1 disrupted the co-localization of these proteins in EPCs treated with TGF-β1. Lenti-FoxO3a shRNA transfection of EPCs suppressed expression of FoxO3a as well as that of the mesenchymal markers SM22α and α-SMA. Conclusions: Activation of PI3K/Akt signaling by Lenti-PIK3R2 shRNA or by exogenous IGF-1 inhibits EndMT in EPCs via negative regulation of FoxO3a-dependent signaling.
Distinct Testicular Steroidogenic Response Mechanisms Between Neonatal and Adult Heat-Acclimated Male Rats
Authors: Kurowicka Beata , Chrusciel Marcin , Zmijewska Agata , Doroszko Milena , Kotwica Genowefa , Rahman Nafis A.
Published: June 2015

Background: In comparison to short-term gonad heat exposure, little is known about the molecular mechanisms that regulate testicular steroidogenesis during long-term whole body heat acclimation. Material and Methods: Testicular slices from neonatal (NHA) and adult (AHA) heat-acclimated Wistar rats were analysed in vitro to assess the mRNA expression and enzymatic activity of steroidogenic enzymes under basal and luteinising hormone (LH) or prolactin (PRL) stimulated conditions compared with control rats (CR). Furthermore, a de-acclimated group (DA) was created by transferring adult NHA rats to control conditions. Results: Heat acclimation significantly increased plasma LH levels in the AHA group and LH and PRL in the NHA group compared with the CR group; however, after heat acclimation, the T and E2 levels did not differ from the control levels. All heat-acclimated groups showed high basal intra-testicular steroid production in vitro. Moreover, basal Cyp11a1 and Hsd3b1 levels were upregulated in vitro in the NHA and DA groups versus the CR group. LH in vitro stimulation upregulated Cyp11a1 expression in the NHA and AHA groups and PRL stimulation upregulated Cyp17a1 levels in the NHA and DA groups compared with the basal expression levels. In the AHA group, decreased basal Star and CYP11A activities but increased HSD3B1 and CYP17A1 activities were found. Conclusion: Our data revealed that despite the similar steroid levels in plasma and secreted in vitro by neonatal and adult heat-acclimated rat testicular slices, the molecular mechanisms underlying the steroidogenic response to heat acclimation during these different developmental stages were distinct.
Acute Doxorubicin-Induced Cardiotoxicity is Associated with Matrix Metalloproteinase-2 Alterations in Rats
Authors: Polegato Bertha Furlan , Minicucci Marcos Ferreira , Azevedo Paula Schmidt , Carvalho Robson Francisco , Chiuso-Minicucci Fernanda , Pereira Elenize Jamas , Paiva Sergio Alberto Rupp , Zornoff Leonardo Antônio Mamede , Okoshi Marina Politi , Matsubara Beatriz Bojikian , Matsubara Luiz Shiguero
Published: June 2015

Background: Doxorubicin can cause cardiotoxicity. Matrix metalloproteinases (MMP) are responsible for degrading extracellular matrix components which play a role in ventricular dilation. Increased MMP activity occurs after chronic doxorubicin treatment. In this study we evaluated in vivo and in vitro cardiac function in rats with acute doxorubicin treatment, and examined myocardial MMP and inflammatory activation, and gene expression of proteins involved in myocyte calcium transients. Methods: Wistar rats were injected with doxorubicin (Doxo, 20 mg/kg) or saline (Control). Echocardiogram was performed 48 h after treatment. Myocardial function was assessed in vitro in Langendorff preparation. Results: In left ventricle, doxorubicin impaired fractional shortening (Control 0.59±0.07; Doxo 0.51±0.05; p<0.001), and increased isovolumetric relaxation time (Control 20.3±4.3; Doxo 24.7±4.2 ms; p=0.007) and myocardial passive stiffness. MMP-2 activity, evaluated by zymography, was increased in Doxo (Control 141338 ± 8924; Doxo 188874 ± 7652 arbitrary units; p<0.001). There were no changes in TNF-α, INF-γ, IL-10, and ICAM-1 myocardial levels. Expression of phospholamban, Serca-2a, and ryanodine receptor did not differ between groups. Conclusion: Acute doxorubicin administration induces in vivo left ventricular dysfunction and in vitro increased myocardial passive stiffness in rats. Cardiac dysfunction is related to myocardial MMP-2 activation. Increased inflammatory stimulation or changed expression of the proteins involved in intracellular calcium transients is not involved in acute cardiac dysfunction.
SI113, a Specific Inhibitor of the Sgk1 Kinase Activity that Counteracts Cancer Cell Proliferation
Authors: D''Antona Lucia , Amato Rosario , Talarico Cristina , Ortuso Francesco , Menniti Miranda , Dattilo Vincenzo , Iuliano Rodolfo , Gigliotti Francesco , Artese Anna , Costa Giosuè , Schenone Silvia , Musumeci Francesca , Abbruzzese Claudia , Botta Lorenzo , Trapasso Francesco , Alcaro Stefano , Paggi Marco G. , Perrotti Nicola
Published: June 2015

Background/Aims: Published observations on serum and glucocorticoid regulated kinase 1 (Sgk1) knockout murine models and Sgk1-specific RNA silencing in the RKO human colon carcinoma cell line point to this kinase as a central player in colon carcinogenesis and in resistance to taxanes. Methods: By in vitro kinase activity inhibition assays, cell cycle and viability analysis in human cancer model systems, we describe the biologic effects of a recently identified kinase inhibitor, SI113, characterized by a substituted pyrazolo[3,4-d]pyrimidine scaffold, that shows specificity for Sgk1. Results: SI113 was able to inhibit in vitro cell growth in cancer cells derived from tumors with different origins. In RKO cells, this kinase inhibitor blocked insulin-dependent phosphorylation of the Sgk1 substrate Mdm2, the main regulator of p53 protein stability, and induced necrosis and apoptosis when used as a single agent. Finally, SI113 potentiated the effects of paclitaxel on cell viability. Conclusion: Since SI113 appears to be effective in inducing cell death in RKO cells, potentiating paclitaxel sensitivity, we believe that this new molecule could be efficiently employed, alone or in combination with paclitaxel, in colon cancer chemotherapy.
Sonic Hedgehog Signaling Mediates Resveratrol to Increase Proliferation of Neural Stem Cells After Oxygen-Glucose Deprivation/Reoxygenation Injury in Vitro
Authors: Cheng Wei , Yu Pingping , Wang Li , Shen Changbo , Song Xiaosong , Chen Jixiang , Tang Fanren , Yang Qin
Published: June 2015

Background/Aims: There is interest in drugs and rehabilitation methods to enhance neurogenesis and improve neurological function after brain injury or degeneration. Resveratrol may enhance hippocampal neurogenesis and improve hippocampal atrophy in chronic fatigue mice and prenatally stressed rats. However, its effect and mechanism of neurogenesis after stroke is less well understood. Sonic hedgehog (Shh) signaling is crucial for neurogenesis in the embryonic and adult brain, but relatively little is known about the role of Shh signaling in resveratrol-enhanced neurogenesis after stroke. Methods: Neural stem cells (NSCs) before oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro were pretreated with resveratrol with or without cyclopamine. Survival and proliferation of NSCs was assessed by the CCK8 assay and BrdU immunocytochemical staining. The expressions and activity of signaling proteins and mRNAs were detected by immunocytochemistry, Western blotting, and RT-PCR analysis. Results: Resveratrol significantly increased NSCs survival and proliferation in a concentration-dependent manner after OGD/R injury in vitro. At the same time, the expression of Patched-1, Smoothened (Smo), and Gli-1 proteins and mRNAs was upregulated, and Gli-1 entered the nucleus, which was inhibited by cyclopamine, a Smo inhibitor. Conclusion: Shh signaling mediates resveratrol to increase NSCs proliferation after OGD/R injury in vitro.
Natural Antioxidants Improve Red Blood Cell “Survival” in Non-Leukoreduced Blood Samples
Authors: Kucherenko Yuliya V , Bernhardt Ingolf
Published: June 2015

Background: Blood collected in an anticoagulant can be kept refrigerated in an unmodified state within 5 - 6 weeks. Oxidative damage is considered to be a one of the major factors contributing to the development of storage lesions. Lipid and membrane proteins oxidation results in changes in cation gradients that affect the cell survival. Aim: In the present study we used the natural antioxidants and ion channels blockers (L-carnosine, spermine, phloretin and their mixtures) to prolong “survival” of red blood cells (RBCs), measured as the lack of PS exposure and cell hemolysis, in the Alsever's preservative solution upon hypothermic storage. Results: We show that the mixture of carnosine (20 mM), spermine (20 µM) and phloretin (100 µM) effectively blunted phosphatidylserine (PS) exposure, Ca2+ accumulation and RBCs hemolysis in non-leukoreduced low (∼2%) hematocrit samples after 36 days of storage as well as after 1 day of post-storage incubation of the stored cells in physiological saline solution. In addition, a slight but significant decrease in PS exposure was observed in non-leukoreduced high (∼20%) hematocrit samples after 36 days of storage with the mixture of substances. Conclusion: We conclude that the use of the mixture of natural antioxidants (carnosine, spermine, and phloretin) as an additive to blood preservative solution provides better RBCs storage and “survival”.
Spectrocolourimetry Visualized Differences in Sexual Skin Colouration in Macaques
Authors: Ono Eiri , Suzuki Juri , Ishida Takafumi
Published: June 2015

The females of some catarrhines develop conspicuous sexual skin transformations in their hind limbs. Among macaques (one of the radiated and adapted catarrhine groups with diversified sexual skin transformations), differences in sexual skin colouration between the Japanese macaque Macaca fuscata and the rhesus macaque M. mulatta have not been quantitatively analysed. In this study, the sexual skin colouration of these macaques was spectrocolourimetrically measured in the non-mating season (NMS) and the mating season (MS) and represented in a CIELAB space with the variables L*, a* and b*. The variables L*, a* and b* represent positions on the light-dark, red/magenta-green, and yellow-blue axes, respectively. In the Japanese macaques the average ± SD of L*, a* and b* was 53.61 ± 3.31, 11.51 ± 4.57 and 6.66 ± 2.25 in the NMS and 46.60 ± 2.78, 19.97 ± 2.99 and 8.80 ± 1.34 in the MS, respectively, while in the rhesus macaques the average ± SD of L*, a* and b* was 60.09 ± 3.96, 5.99 ± 4.59 and 5.83 ± 2.37 in the NMS and 52.70 ± 6.54, 13.62 ± 6.86 and 8.07 ± 1.43 in the MS, respectively. The sexual skin of the Japanese macaques was consistently much redder (larger a*) and darker (smaller L*) than that of the rhesus macaques. The smaller L* suggested a greater dermal melanin content in the Japanese macaques. These closely related macaque species have similar but distinct sexual skin colourations. Spectrocolourimetry is thus useful to suggest the histophysiological background of the colouration.
Cardiac Toxicity after Radiotherapy for Breast Cancer: Myths and Facts
Authors: Nitsche Mirko , Pahl René , Huber Karen , Eilf Kirsten , Dunst Juergen
Published: June 2015

Radiotherapy is an important component in the multidisciplinary treatment of breast cancer. In recent years, the cardiac risks of radiation have been discussed several times. This problem has long been known and resolved from the radiotherapeutic point of view. The current data is briefly described here.
Prematurity, Opioid Exposure and Neonatal Pain: Do They Affect the Developing Brain?
Authors: van den Bosch Gerbrich E. , White Tonya , El Marroun Hanan , Simons Sinno H.P. , van der Lugt Aad , van der Geest Jos N. , Tibboel Dick , van Dijk Monique
Published: June 2015

Background: Traditionally, 10 years ago, children born preterm often routinely received morphine, especially during mechanical ventilation. Studies in neonatal rats, whose stage of brain development roughly corresponds to that of children born preterm, found negative long-term effects after pain and opioid exposure. Objectives: We studied possible effects of prematurity, procedural pain and opioids in humans 10 years later. We hypothesized that these factors would negatively influence neurobiological, neuropsychological and sensory development later in life. Methods: We included 19 children born preterm who as neonates participated in an RCT on the short-term effects of morphine administration and who previously participated in our follow-up studies at ages 5 and 8/9 years. We assessed associations between brain morphology (n = 11), neuropsychological functioning (n = 19) and thermal sensitivity (n = 17) and prematurity, opioid exposure and neonatal pain. Results: Significant correlations (coefficients 0.60-0.85) of gestational age, number of painful procedures and morphine exposure with brain volumes were observed. Significant correlations between these factors and thermal sensitivity were not established. Neuropsychological outcome was significantly moderately correlated with morphine exposure in only two subtests, and children performed in general ‘average' by Dutch norms. Conclusions: Although prematurity, opioid exposure and neonatal pain were significantly associated with brain volume, no major associations with neuropsychological functioning or thermal sensitivity were detected. Our findings suggest that morphine administration during neonatal life does not affect neurocognitive performance or thermal sensitivity during childhood in children born preterm without brain damage during early life. Future studies with larger sample sizes are needed to confirm these findings.
Has Previous Abuse of Flunitrazepam Been Replaced by Clonazepam?
Authors: Høiseth Gudrun , Middelkoop Gerrit , Mørland Jørg , Gjerde Hallvard
Published: June 2015

Background and Aims: For many years, flunitrazepam was the benzodiazepine of choice among users of illegal drugs. The aim of this study was to investigate to which extent clonazepam use has increased in this population, and whether this was related to increased prescription or because of illegal availability. Methods: We used data from three sources to study the changes in the use of clonazepam: (1) Presence and concentrations of clonazepam and flunitrazepam in blood samples collected from Norwegian drugged drivers; (2) Sales numbers (legal market) for clonazepam, extracted from the Norwegian prescription database (NorPD), and (3) Specific seizures (illegal market) for clonazepam in Norway. Results: In 2004, 13.0% of the analysed blood samples from drugged drivers contained clonazepam, whereas this proportion had increased to 27.7% in 2013. In the same period, the frequency of flunitrazepam in drugged drivers decreased from 16.6% in 2004 to 3.2% in 2013. The number of clonazepam prescriptions decreased, while the number of seized tablets containing clonazepam increased considerably from 2004 to 2013. Conclusions: For the last 10 years, a significant increase in the illegal use of clonazepam has been seen, now replacing flunitrazepam as the most used illegal benzodiazepine in Norway.
The Evolution of Relative Brain Size in Marsupials Is Energetically Constrained but Not Driven by Behavioral Complexity
Authors: Weisbecker Vera , Blomberg Simon , Goldizen Anne W. , Brown Meredeth , Fisher Diana
Published: June 2015

Evolutionary increases in mammalian brain size relative to body size are energetically costly but are also thought to confer selective advantages by permitting the evolution of cognitively complex behaviors. However, many suggested associations between brain size and specific behaviors - particularly related to social complexity - are possibly confounded by the reproductive diversity of placental mammals, whose brain size evolution is the most frequently studied. Based on a phylogenetic generalized least squares analysis of a data set on the reproductively homogenous clade of marsupials, we provide the first quantitative comparison of two hypotheses based on energetic constraints (maternal investment and seasonality) with two hypotheses that posit behavioral selection on relative brain size (social complexity and environmental interactions). We show that the two behavioral hypotheses have far less support than the constraint hypotheses. The only unambiguous associates of brain size are the constraint variables of litter size and seasonality. We also found no association between brain size and specific behavioral complexity categories within kangaroos, dasyurids, and possums. The largest-brained marsupials after phylogenetic correction are from low-seasonality New Guinea, supporting the notion that low seasonality represents greater nutrition safety for brain maintenance. Alternatively, low seasonality might improve the maternal support of offspring brain growth. The lack of behavioral brain size associates, found here and elsewhere, supports the general ‘cognitive buffer hypothesis' as the best explanatory framework of mammalian brain size evolution. However, it is possible that brain size alone simply does not provide sufficient resolution on the question of how brain morphology and cognitive capacities coevolve.
Comparison of Three Cognitive Screening Tools in Older Urban and Regional Aboriginal Australians
Authors: Radford Kylie , Mack Holly A. , Draper Brian , Chalkley Simon , Delbaere Kim , Daylight Gail , Cumming Robert G. , Bennett Hayley , Broe Gerald A.
Published: June 2015

Background: Validated cognitive screening tools for use in urban and regional Aboriginal populations in Australia are lacking. Methods: In a cross-sectional community-based study, 235 participants were assessed on the Mini-Mental State Examination (MMSE), the Rowland Universal Dementia Assessment Scale (RUDAS) and an urban modification of the Kimberley Indigenous Cognitive Assessment (mKICA). Performance on these cognitive screening tools was compared to dementia diagnosis by clinical consensus. Results: All tests were culturally acceptable with good psychometric properties. Receiver operating characteristic curve analyses revealed that the MMSE and mKICA were the most accurate. Conclusion: The MMSE is an effective cognitive screening tool in urban Aboriginal populations. The mKICA is a good alternative when illiteracy, language or cultural considerations deem it appropriate. The RUDAS also has adequate validity in this population.
Early Integration Processing between Faces and Vowel Sounds in Human Brain: An MEG Investigation
Authors: Nakamura Itta , Hirano Yoji , Ohara Naotoshi , Hirano Shogo , Ueno Takefumi , Tsuchimoto Rikako , Kanba Shigenobu , Onitsuka Toshiaki
Published: June 2015

Objective: Unconscious fast integration of face and voice information is a crucial brain function necessary for communicating effectively with others. Here, we investigated for evidence of rapid face-voice integration in the auditory cortex. Methods: Magnetic fields (P50m and N100m) evoked by visual stimuli (V), auditory stimuli (A) and audiovisual stimuli (VA), i.e. by face, vowel and simultaneous vowel-face stimuli, were recorded in 22 healthy subjects. Magnetoencephalographic data from 28 channels around bilateral auditory cortices were analyzed. Results: In both hemispheres, AV - V showed significantly larger P50m amplitudes than A. Additionally, compared with A, the N100m amplitudes and dipole moments of AV - V were significantly smaller in the left hemisphere, but not in the right hemisphere. Conclusions: Differential changes in P50m (bilateral) and N100m (left hemisphere) that occur when V (faces) are associated with A (vowel sounds) indicate that AV (face-voice) integration occurs in early processing, likely enabling us to communicate effectively in our lives.
Cerebral Microbleeds and White Matter Hyperintensities in Cognitively Healthy Elderly: A Cross-Sectional Cohort Study Evaluating the Effect of Arterial Stiffness
Authors: Gustavsson Anna-Märta , Stomrud Erik , Abul-Kasim Kasim , Minthon Lennart , Nilsson Peter M. , Hansson Oskar , Nägga Katarina
Published: June 2015

Background: Arterial stiffness reflects the ageing processes in the vascular system, and studies have shown an association between reduced cognitive function and cerebral small vessel disease. Small vessel disease can be visualized as white matter hyperintensities (WMH) and lacunar infarcts but also as cerebral microbleeds on brain magnetic resonance imaging (MRI). We aimed to investigate if arterial stiffness influences the presence of microbleeds, WMH and cognitive function in a population of cognitively healthy elderly. Methods: The study population is part of the Swedish BioFinder study and consisted of 208 individuals without any symptoms of cognitive impairment, who scored >27 points on the Mini-Mental State Examination. The participants (mean age, 72 years; 59% women) underwent MRI of the brain with visual rating of microbleeds and WMH. Arterial stiffness was measured with carotid-femoral pulse wave velocity (cfPWV). Eight cognitive tests covering different cognitive domains were performed. Results: Microbleeds were detected in 12% and WMH in 31% of the participants. Mean (±standard deviation, SD) cfPWV was 10.0 (±2.0) m/s. There was no association between the presence of microbleeds and arterial stiffness. There was a positive association between arterial stiffness and WMH independent of age or sex (odds ratio, 1.58; 95% confidence interval, 1.04-2.40, p < 0.05), but the effect was attenuated when further adjustments for several cardiovascular risk factors were performed (p > 0.05). Cognitive performance was not associated with microbleeds, but individuals with WMH performed slightly worse than those without WMH on the Symbol Digit Modalities Test (mean ± SD, 35 ± 7.8 vs. 39 ± 8.1, p < 0.05). Linear regression revealed no direct associations between arterial stiffness and the results of the cognitive tests. Conclusions: Arterial stiffness was not associated with the presence of cerebral microbleeds or cognitive function in cognitively healthy elderly. However, arterial stiffness was related to the presence of WMH, but the association was attenuated when multiple adjustments were made. There was a weak negative association between WMH and performance in one specific test of attention. Longitudinal follow-up studies are needed to further assess the associations.
A Neuroimaging Strategy for the Three-Dimensional in vivo Anatomical Visualization and Characterization of Insular Gyri
Authors: Rosen Allison , Chen David Qixiang , Hayes Dave J. , Davis Karen D. , Hodaie Mojgan
Published: June 2015

Background: Interest in the anatomy of the insula is driven by its multifunctionality and the need for accurate visualization for surgical purposes. Few in vivo studies of human insular anatomy have been conducted due to methodological and anatomical challenges. Objective: We used brain cortical morphometry tools to accurately reconstruct insular topology and permit a detailed visualization of its gyri in 3 dimensions. Methods: Sixty healthy subjects (33 females; 37.8 ± 12.8 years) underwent 3-tesla MRI scans. The strategy for characterizing the insula was: (1) create 3-dimensional (3-D) insula representations for visual analysis; (2) rate topological features using a gyral conspicuity index; (3) identify individual variations across subjects/between groups; (4) compare to prior findings. Results: Insular reconstruction was achieved in 113/120 cases. The anterior short, posterior short, anterior long gyri and central sulcus were easily identified. In contrast, middle short (MSG), posterior long (PLG) and accessory gyri (AG) were highly variable. The MSG, but not the PLG or AG, was clearer in males and in the left hemisphere, suggesting sex- and laterality-related differences. Conclusions: A noninvasive in vivo 3-D visualization strategy revealed anatomical variations of the insula in a healthy cohort. This methodological approach can be adopted for broad clinical and/or research purposes.
Longitudinal Evaluation of the Structural Integrity of Teeth Affected by Molar Incisor Hypomineralisation
Authors: Bullio Fragelli Camila Maria , Jeremias Fabiano , Feltrin de Souza Juliana , Paschoal Marco Aurélio , de Cássia Loiola Cordeiro Rita , Santos-Pinto Lourdes
Published: June 2015

The aim of this prospective cohort study was to evaluate the risk of posteruptive breakdown and the development of caries lesions in teeth with molar incisor hypomineralisation (MIH). A total of 367 permanent incisors and first molars, affected and not affected by MIH lesions, of 45 children with MIH from Araraquara, São Paulo, Brazil, were evaluated at intervals from 6 to 12 months by assessing the severity of MIH, the presence of tooth caries lesions and the treatment needed. During the study period, all patients received preventive care. The data were analysed using Fisher's exact test and actuarial method survival analysis. Significant associations were also found in teeth between the presence of MIH and a DMFT index >0 in all periods and also between the need for treatment and the presence of MIH. The teeth affected by MIH opacities were healthy in 99% of incisors and 93% of molars at the end of the 12-month period. Due to the high likelihood of maintaining the tooth structure in opacities, the complete or premature removal of the affected area is not justified.
An Idiopathic Leukonychia Totalis and Leukonychia Partialis Case Report and Review of the Literature
Authors: Canavan Theresa , Tosti Antonella , Mallory Hurst , McKay Kristopher , Cantrell Wendy , Elewski Boni
Published: June 2015

Leukonychia totalis and leukonychia partialis are rare nail findings characterized by complete or partial whitening of the nail plate. Leukonychia totalis and leukonychia partialis are usually inherited or associated with systemic disease. Here, we report the case of a 25-year-old man with idiopathic acquired leukonychia totalis and leukonychia partialis and review the literature on this topic.
Verbal Cognition in Deaf Children Using Cochlear Implants: Effect of Unilateral and Bilateral Stimulation
Authors: De Raeve Leo , Vermeulen Anneke , Snik Ad
Published: June 2015

The aim of this study is to assess the role of bilateral/bimodal device use in auditory speech perception in complex listening situations and long-term verbal cognition in deaf children using cochlear implants (CIs). Two groups of children are compared (unilateral and bilateral device users) concerning vocabulary, speech perception at conversational level and in complex listening situations, and verbal cognition. In this retrospective study, we collected data of 37 deaf children with normal learning potential of whom 16 were unilateral CI users and 21 were bilateral device users (9 with a bimodal fitting and 12 with bilateral CIs). We came to the conclusion that deaf children who use bilateral devices have the opportunity to develop good speech perception skills in complex listening conditions. These abilities enable at least some of the children to develop age-equivalent verbal cognition skills.
Quantitative EEG Applying the Statistical Recognition Pattern Method: A Useful Tool in Dementia Diagnostic Workup
Authors: Engedal Knut , Snaedal Jon , Hoegh Peter , Jelic Vesna , Bo Andersen Birgitte , Naik Mala , Wahlund Lars-Olof , Oeksengaard Anne-Rita
Published: June 2015

Background/Aim: The aim of this study was to examine the discriminatory power of quantitative EEG (qEEG) applying the statistical pattern recognition (SPR) method to separate Alzheimer's disease (AD) patients from elderly individuals without dementia and from other dementia patients. Methods: The participants were recruited from 6 Nordic memory clinics: 372 unselected patients [mean age 71.7 years (SD 8.6), 54% women] and 146 healthy elderly individuals [mean age 66.5 years (SD 7.7), 60% women]. After a standardized and comprehensive assessment, clinical diagnoses were made according to internationally accepted criteria by at least 2 clinicians. EEGs were recorded in a standardized way and analyzed independently of the clinical diagnoses, using the SPR method. Results: In receiver operating characteristic curve analyses, the qEEGs separated AD patients from healthy elderly individuals with an area under the curve (AUC) of 0.90, representing a sensitivity of 84% and a specificity of 81%. The qEEGs further separated patients with Lewy body dementia or Parkinson's disease dementia from AD patients with an AUC of 0.9, a sensitivity of 85% and a specificity of 87%. Conclusion: qEEG using the SPR method could be a useful tool in dementia diagnostic workup.