bluuebunny/crossref_metadata_2025 huggingface dataset:
SK channel-selective opening by SKA-31 induces hyperpolarization and decreases contractility in human urinary bladder smooth muscle
Authors: Soder Rupal P. , Parajuli Shankar P. , Hristov Kiril L. , Rovner Eric S. , Petkov Georgi V.
Published: November 2012

Overactive bladder (OAB) is often associated with increased involuntary detrusor smooth muscle (DSM) contractions during the bladder-filling phase. To develop novel therapies for OAB, it is critical to better understand the mechanisms that control DSM excitability and contractility. Recent studies showed that small-conductance Ca2+-activated K+(SK) channels, SK3 channels, in particular, regulate human DSM function. However, the concept that SK channel-selective pharmacological activation can decrease the excitability and contractility directly in human DSM needs further exploration. Here, we studied the effect of the novel and potent SK channel activator, SKA-31 (or naphtho [1,2- d]thiazol-2-ylamine), on human DSM excitability and contractility at the cellular and tissue level. We used isometric tension recordings on human DSM-isolated strips and the perforated patch-clamp technique on freshly isolated native human DSM cells. SKA-31 significantly decreased spontaneous phasic contractions of DSM-isolated strips. In the presence of the SK channel blocker, apamin, the inhibitory effects of SKA-31 on the DSM spontaneous phasic contractions were significantly reduced. SKA-31 decreased the carbachol- and KCl-induced contractions in human DSM strips. Electrical field stimulation-induced contractions were significantly attenuated in the presence of SKA-31 at all stimulation frequencies (0.5–50 Hz). SKA-31 hyperpolarized the resting membrane potential of human DSM cells. Apamin abolished the hyperpolarizing effect of SKA-31, indicating the involvement of SK channel activation. These results support the concept that pharmacological activation of SK channels with selective openers may represent an attractive new pharmacological approach for decreasing DSM excitability and contractility, thus controlling OAB.
Feedback inhibition of ENaC during acute sodium loading in vivo
Authors: Patel Ankit B. , Frindt Gustavo , Palmer Lawrence G.
Published: November 2012

The epithelial Na+channel (ENaC) is tightly regulated by sodium intake to maintain whole body sodium homeostasis. In addition, ENaC is inhibited by high levels of intracellular Na+[Na+]i, presumably to prevent cell Na+overload and swelling. However, it is not clear if this regulation is relevant in vivo. We show here that in rats, an acute (4 h) oral sodium load decreases whole-cell amiloride-sensitive currents ( INa) in the cortical collecting duct (CCD) even when plasma aldosterone levels are maintained high by infusing the hormone. This was accompanied by decreases in whole-kidney cleaved α-ENaC (2.6 fold), total β-ENaC (1.7 fold), and cleaved γ-ENaC (6.2 fold). In addition, cell-surface β- and γ-ENaC expression was measured using in situ biotinylation. There was a decrease in cell-surface core-glycosylated (2.2 fold) and maturely glycosylated (4.9 fold) β-ENaC and cleaved γ-ENaC (4.7 fold). There were no significant changes for other apical sodium transporters. To investigate the role of increases in Na+entry and presumably [Na+]ion ENaC, animals were infused with amiloride prior to and during sodium loading. Blocking Na+entry did not inhibit the effect of resalting on INa. However, amiloride did prevent decreases in ENaC expression, an effect that was not mimicked by hydrochlorothiazide administration. Na+entry and presumably [Na+]ican regulate ENaC expression but does not fully account for the aldosterone-independent decrease in INaduring an acute sodium load.
Involvement of cytochrome epoxygenase metabolites in cutaneous postocclusive hyperemia in humans
Authors: Cracowski Jean-Luc , Gaillard-Bigot Florence , Cracowski Claire , Sors Claire , Roustit Matthieu , Millet Claire
Published: November 2012

Several mediators contribute to postocclusive reactive hyperemia (PORH) of the skin, including sensory nerves and endothelium-derived hyperpolarizing factors. The main objective of our study was to investigate the specific contribution of epoxyeicosatrienoic acids in human skin PORH. Eight healthy volunteers were enrolled in two placebo-controlled experiments. In the first experiment we studied the separate and combined effects of 6.5 mM fluconazole, infused through microdialysis fibers, and lidocaine/prilocaine cream on skin PORH following 5 min arterial occlusion. In the second experiment we studied the separate and combined effects of 6.5 mM fluconazole and 10 mM NG-monomethyl-l-arginine (l-NMMA). Skin blood flux was recorded using two-dimensional laser speckle contrast imaging. Maximal cutaneous vascular conductance (CVCmax) was obtained following 29 mM sodium nitroprusside perfusion. The PORH peak at the placebo site averaged 66 ± 11%CVCmax. Compared with the placebo site, the peak was significantly lower at the fluconazole (47 ± 10%CVCmax; P < 0.001), lidocaine (29 ± 10%CVCmax; P < 0.001), and fluconazole + lidocaine (30 ± 10%CVCmax; P < 0.001) sites. The effect of fluconazole on the area under the curve was more pronounced. In the second experiment, the PORH peak was significantly lower at the fluconazole site, but not at the l-NMMA or combination site, compared with the placebo site. In addition to sensory nerves cytochrome epoxygenase metabolites, putatively epoxyeicosatrienoic acids, play a major role in healthy skin PORH, their role being more important in the time course rather than the peak.
Characterization of respiratory neurons in the rostral ventrolateral medulla, an area critical for vocal production in songbirds
Authors: McLean Judith , Bricault Sarah , Schmidt Marc F.
Published: November 2012

Much is known about the neuronal cell types and circuitry of the mammalian respiratory brainstem and its role in normal, quiet breathing. Our understanding of the role of respiration in the context of vocal production, however, is very limited. Songbirds contain a well-defined neural circuit, known as the song system, which is necessary for song production and is strongly coupled to the respiratory system. A major target of this system is nucleus parambigualis (PAm) in the ventrolateral medulla, a structure that controls inspiration by way of its bulbospinal projections but is also an integral part of the song-pattern generation circuit by way of its “thalamocortical” projections to song-control nuclei in the telencephalon. We have mapped out PAm to characterize the cell types and its functional organization. Extracellular single units were obtained in anesthetized adult male zebra finches while measuring air sac pressure to monitor respiration. Single units were characterized by their discharge patterns and the phase of the activity in the respiratory cycle. Several classes of neurons were identified and were analogous to those reported for mammalian medullary respiratory neurons. The majority of the neurons in PAm was classified as inspiratory augmenting or preinspiratory, although other basic discharge patterns were observed as well. The well-characterized connectivity of PAm within the vocal motor circuit and the similarity of its neural firing patterns to the rostral ventral respiratory group and pre-Bötzinger complex of mammals make it an ideal system for investigating the integration of breathing and vocalization.
Variation in sodium current amplitude between vasopressin and oxytocin hypothalamic supraoptic neurons
Authors: Scroggs Reese , Wang Lie , Teruyama Ryoichi , Armstrong William E.
Published: November 2012

Biophysical characteristics of tetrodotoxin-sensitive sodium (Na+) currents were studied in vasopressin (VP) and oxytocin (OT) supraoptic neurons acutely isolated from rat hypothalamus. Na+ current density (pA/pF) was significantly greater in VP neurons than in OT neurons. No significant difference between VP and OT neurons was detected regarding the voltage dependence of activation and steady-state inactivation, or rate of recovery from inactivation of Na+ currents. In both VP and OT neurons, the macroscopic inactivation of the Na+ currents was best fitted with a double-exponential expression suggesting two rates of inactivation. Also in both types, the time course of recovery from inactivation proceeded with fast and slow time constants averaging around 8 and 350 ms, respectively, suggesting the presence of multiple pathways of recovery from inactivation. The slower time constant of recovery of inactivation may be involved in the decrease in action potential (AP) amplitude that occurs after the first spike during burst firing in both neuronal types. The larger amplitude of Na+ currents in VP vs. OT neurons may explain the previous observations that VP neurons exhibit a lower AP threshold and greater AP amplitude than OT neurons, and may serve to differently tune the firing properties and responses to neuromodulators of the respective neuronal types.
Influence of Drying Temperature on the Structural, Optical, and Electrical Properties of Layer‐by‐Layer ZnO Nanoparticles Seeded Catalyst
Authors: Shariffudin S. S. , Mamat M. H. , Herman S. H. , Rusop M.
Published: November 2012

Layer‐by‐layer zinc oxide (ZnO) nanoparticles have been prepared using sol‐gel spin coating technique. The films were dried at different temperature from 100°C to 300°C to study its effect to the surface morphology, optical and electrical properties of the films. Film dried at 200°C shows the highest (0 0 2) peak of X‐ray diffraction pattern which is due to complete decomposition of zinc acetate and complete vaporization of the stabilizer and solvent. It was found that the grain size increased with the increased of drying temperature from 100 to 200°C, but for films dried at above 200°C, the grain size decreased. Photoluminescence measurements show a sharp ultraviolet emission centred at 380 nm and a very low intensity visible emission. Blue visible emission was detected for sample dried at temperature below 200°C, while for films dried above 250°C, the visible emission is red shifted. The films were transparent in the visible range from 400 to 800 nm with average transmittance of above 85%. Linear I‐V characteristics were shown confirming the ohmic behaviour of the gold contacts to the films. A minimum resistivity was given by 5.08 Ω · cm for the film dried at 300°C.
Math Anxiety Questionnaire: Similar Latent Structure in Brazilian and German School Children
Authors: Wood Guilherme , Pinheiro-Chagas Pedro , Júlio-Costa Annelise , Micheli Letícia Rettore , Krinzinger Helga , Kaufmann Liane , Willmes Klaus , Haase Vitor Geraldi
Published: November 2012

Math anxiety is a relatively frequent phenomenon often related to low mathematics achievement and dyscalculia. In the present study, the German and the Brazilian versions of the Mathematics Anxiety Questionnaire (MAQ) were examined. The two-dimensional structure originally reported for the German MAQ, that includes both affective and cognitive components of math anxiety was reproduced in the Brazilian version. Moreover, mathematics anxiety also was found to increase with age in both populations and was particularly associated with basic numeric competencies and more complex arithmetics. The present results suggest that mathematics anxiety as measured by the MAQ presents the same internal structure in culturally very different populations.
Mechanism of Earthquake Simulation as a Prenatal Stressor Retarding Rat Offspring Development and Chinese Medicine Correcting the Retardation: Hormones and Gene-Expression Alteration
Authors: Zhang X. G. , Zhang H. , Tan R. , Peng J. C. , Liang X. L. , Liu Q. , Wang M. Q. , Yu X. P.
Published: November 2012

We aimed to investigate the mechanism of shaking as a prenatal stressor impacting the development of the offspring and Chinese medicines correcting the alterations. Pregnant rats were randomized into earthquake simulation group (ESG), herbal group (HG) which received herbal supplements in feed after shaking, and control group (CG). Findings revealed body weight and open field test (OFT) score of ESG offspring were statistically inferior to the CG and HG offspring. The corticosterone levels of ESG were higher than those of CG but not than HG. The dopamine level of ESG was slightly lower than that of the CG and of HG was higher than that of ESG. The 5-HT of ESG was higher than CG and HG. The growth hormone level of the ESG was significantly lower than ESG but not than CG. Gene expression profile showed 81 genes upregulated and 39 genes downregulated in ESG versus CG, and 60 genes upregulated and 28 genes downregulated in ESG versus HG. Eighty-four genes were found differentially expressed in ESG versus CG comparison and were normalized in ESG versus HG. We conclude that maternal shaking negatively affected physical and nervous system development, with specific alterations in neurohormones and gene expression. Chinese herbal medicine reduced these negative outcomes.
High Gain Array of Monopoles-Coupled Antennas for Wireless Applications
Authors: El Sayed Ahmad Ahmad , Thevenot Marc , Floc'h Jean-Marie , Mantash Mohamad
Published: November 2012

An array of monopole antennas over a ground plane that radiates a directive lobe in the end-fire direction are described in this paper. The design uses the rigorous method described by Drouet et al. 2008 in order to synthesize the radiation through the strong cumulative coupling between the monopoles. A gain higher than 20 dB was achieved in the end-fire direction over a 4.5% bandwidth. However, the antenna has been tilted in order to compensate the beam deviation caused by the edge diffraction. A prototype with 12 elements has been manufactured in order to validate the antenna principle and the whole antenna is successfully measured. The prototype was studied with the software CST-Microwave Studio and the feed network has been designed with Agilent ADS.
Intermediate- and Low-Methylation Epigenotypes Do Not Correspond to CpG Island Methylator Phenotype (Low and -Zero) in Colorectal Cancer
Authors: Karpinski Pawel , Walter Michael , Szmida Elzbieta , Ramsey David , Misiak Blazej , Kozlowska Joanna , Bebenek Marek , Grzebieniak Zygmunt , Blin Nikolaus , Laczmanski Lukasz , Sasiadek Maria M.
Published: November 2012

Background: Most recent genome-wide studies on the CpG island methylation in colorectal cancer (CRC) have led to the discovery of at least 3 distinct methylation clusters. However, there remains an uncertainty whether the CRC clusters identified in these studies represent compatible phenotypes.

Methods: We carried out comprehensive genome-scale DNA methylation profiling by Illumina Infinium HumanMethylation27 of 21 DNA pools that represent 84 CRC samples divided according to their high-, intermediate-, and low-methylation epigenotypes (HME, IME, and LME, respectively) and 70 normal-adjacent colonic tissues. We have also examined the relationship among 3 epigenotypes and chromosomal gains and deletions (assessed by Comparative Genomic Hybridization) in a group of 100 CRC samples.

Results: The HME subgroup showed features associated with CpG island methylator phenotype – high (CIMP-high) including methylation of specific CpG sites (CpGs) as well as significantly lower mean number of chromosomal imbalances when compared with other epigenotypes. The IME subgroup displayed the lowest number of methylated CpGs (717 vs. 2,399 and 2,679 in HME and LME, respectively) and highest mean number of chromosomal imbalances when compared with HME (P, 0.001) and LME (P, 0.004). A comparison between the methylation profiles of 3 epigenotypes revealed more similarities between the HME and LME (1,669 methylated CpGs overlapped) than HME and IME (673 methylated CpGs overlapped).

Conclusion: Our results provide evidence that IME and LME CRCs show opposite features to those that have been previously attributed to CIMP-low and CIMP-0 CRCs.

Impact: These discrepancies should be considered when interpreting the data from a particular epigenotyping method. Cancer Epidemiol Biomarkers Prev; 22(2); 201–8. ©2012 AACR.
Diphtheria Toxin–Epidermal Growth Factor Fusion Protein DAB389EGF for the Treatment of Bladder Cancer
Authors: Yang Xiaoping , Kessler Elizabeth , Su Lih-Jen , Thorburn Andrew , Frankel Arthur E. , Li Yuan , La Rosa Francisco G. , Shen Jingping , Li Chuan-Yuan , Varella-Garcia Marileila , Glodé L. Michael , Flaig Thomas W.
Published: November 2012

Purpose: The novel fusion protein, DAB389EGF, is composed of both the catalytic and the translocation domains of diphtheria toxin that are fused to the human EGF, providing a targeting and a toxicity component. We tested DAB389EGF for antitumor activity in both in vitro and in vivo urinary bladder cancer models.

Experimental Design: Human bladder cancer lines were treated with DAB389EGF and assessed for growth inhibition and clonogenic suppression. Using 6- to 8-week-old female athymic nude mice implanted orthotopically with HTB9 cells, DAB389EGF was administered intravesically twice weekly for 2 weeks. The response of the luciferase-expressing HTB9 cells was monitored via bioluminescence as the primary endpoint.

Results: Treatment response with DAB389EGF was specific and robust, with an IC50 ranging from 0.5 to 15 ng/mL in eight tested bladder cancer cell lines, but greater than 50 ng/mL in the EGF receptor (EGFR)-negative H520 control cell line. Simulating short-duration intravesical therapy used clinically, a 2-hour treatment exposure of DAB389EGF (10 ng/mL) produced clonogenic suppression in three selected bladder cancer cell lines. In vivo, luciferase activity was suppressed in five of six mice treated with DAB389EGF [70 μL (1 ng/μL) per mouse], as compared with only one of six mice treated with a control diphtheria toxin (DT) fusion protein. Histologic assessment of tumor clearance correlated with the bioluminescent changes observed with DAB389EGF treatment. Immunocompetent mice treated with intravesical DAB389EGF did not show any nonspecific systemic toxicity.

Conclusions: The intravesical delivery of targeted toxin fusion proteins is a novel treatment approach for non–muscle-invasive urinary bladder cancer. With appropriate targeting, the treatments are effective and well-tolerated in vivo. Clin Cancer Res; 19(1); 148–57. ©2012 AACR.
Contribution of HIF-1α in 4E-BP1 Gene Expression
Authors: Azar Rania , Lasfargues Charline , Bousquet Corinne , Pyronnet Stéphane
Published: November 2012

The eukaryotic translation initiation factor 4E (eIF4E) is necessary for the translation of capped mRNAs into proteins. Cap-dependent mRNA translation can be however inhibited by the eIF4E-binding protein 1 (4E-BP1). The hypophosphorylated forms of 4E-BP1 indeed sequester eIF4E and thus block translation initiation and consequent protein synthesis. Different reports indicate that, in addition to hypophosphorylation, 4E-BP1 function can be also regulated at the level of protein expression. This is the case in contact-inhibited cells or in cells exposed to hypoxia. The molecular mechanisms responsible for 4E-BP1 protein accumulation in these conditions remain however unknown. In the present study, we found that 4E-BP1 gene promoter contains a hypoxia-responsive element (HRE) that mediates 4E-BP1 gene upregulation via the hypoxia-inducible factor-1 alpha (HIF-1α) transcription factor. Gene reporter assays then revealed that the presence of such HRE in the promoter of 4E-BP1 gene is involved in 4E-BP1 accumulation in contact-inhibited cells and in cells exposed to hypoxia. We also reveal that the TGF-β–dependent transcription factor SMAD4 cooperates with HIF-1α to fully activate 4E-BP1 gene transcription under hypoxia. These data therefore suggest that HIF-1α contributes to 4E-BP1 gene expression under different conditions. Mol Cancer Res; 11(1); 54–61. ©2012 AACR.
Targeted Inactivation of HDAC2 Restores p16INK4a Activity and Exerts Antitumor Effects on Human Gastric Cancer
Authors: Kim Jeong Kyu , Noh Ji Heon , Eun Jung Woo , Jung Kwang Hwa , Bae Hyun Jin , Shen Qingyu , Kim Min Gyu , Chang Young Gyoon , Kim Seung-Jin , Park Won Sang , Lee Jung Young , Borlak Jürgen , Nam Suk Woo
Published: November 2012

Aberrant regulation of histone deacetylase 2 (HDAC2) was reported for gastric cancers. However, responsive cancer genes in disease onset and progression are less understood. HDAC2 expression was studied by quantitative RT-PCR and Western blotting. The functional consequences of HDAC2 knockdown on cell-cycle regulation, programmed cell death, and gene target identification was investigated by flow cytometry, Western blotting, electron microscopy, anchorage-independent colony formation, and cell migration assay and by whole-genome microarray. Therapeutic efficacy of HDAC2 knockdown was determined in nude mice with small hairpin expressing human gastric cancer cells. Epigenetic regulation of p16INK4a was studied by methylation-specific PCR and chromatin-IP to evidence HDAC2 or acetylated-histone-H4 binding at gene specific promoter sequences. HDAC2 gene and protein expression was significantly upregulated in different histopathologic grades of human gastric cancers and cancer cell lines. HDAC2 inactivation significantly reduced cell motility, cell invasion, clonal expansion, and tumor growth. HDAC2 knockdown-induced G1–S cell cycle arrest and restored activity of p16INK4a and the proapoptotic factors. This treatment caused PARP cleavage and hypophosphorylation of the Rb-protein, repressed cyclinD1, CDK4, and Bcl-2 expression and induced autophagic phenotype, that is, LC3B-II conversion. Some gastric tumors and cancer cells displayed p16INK4a promoter hypermethylation but treatment with 5-aza-deoxycitidine restored activity. With others the methylation status was unchanged. Here, chromatin-IP evidenced HDAC2 binding. Nonetheless, expression of p16INK4a was restored by HDAC2 knockdown with notable histone-H4-acetylation, as determined by chromatin-IP. Thus, p16INK4a is regulated by HDAC2. HDAC2 is a bona fide target for novel molecular therapies in gastric cancers. Mol Cancer Res; 11(1); 62–73. ©2012 AACR.
Proneness to Decreased Negative Emotions in Major Depressive Disorder when Blaming Others rather than Oneself
Authors: Green Sophie , Moll Jorge , Deakin John F. William , Hulleman Johan , Zahn Roland
Published: November 2012

Background: One widespread view holds that vulnerability to major depressive disorder (MDD) is linked to overall increases in negative emotionality. In contrast, cognitive attribution theories emphasize the importance of blaming oneself rather than others for negative events. Thus far, the contrasting predictions of these models have not been directly compared. Following the attributional perspective, we tested the hypothesis that people with remitted MDD show no overall bias towards negative emotions, but a selective bias towards self-blaming emotions relative to those emotions associated with blaming others. Sampling and Methods: We compared a remitted MDD and a control group on a novel experimental test that allowed us to directly compare proneness to specific emotions associated with different types of self-blame (guilt, shame, self-contempt/disgust) and blame of others (other-indignation/anger, other-contempt/disgust) whilst controlling for negative valence and medication status, and excluding comorbidity. Results: In agreement with our hypothesis, individuals with remitted MDD exhibited an increased self-contempt bias (difference between contempt/disgust towards self and others) but no increased proneness to any other negative emotion or overall increases in perceived negative valence of stimuli. Moreover, the remitted MDD group exhibited reduced contempt/disgust towards others. Conclusions: Our results corroborate the prediction that vulnerability to MDD is associated with an imbalance of specific self- and other-blaming emotions rather than a general increase in negative emotions. Based on the composition of our sample, we speculate that self-contempt bias may be particularly characteristic of melancholic MDD subtypes and could be useful for stratification of depression in the future.
Psychological Symptoms as Long-Term Consequences of War Experiences
Authors: Priebe Stefan , Jankovic Gavrilovic Jelena , Bremner Stephen , Ajdukovic Dean , Franciskovic Tanja , Galeazzi Gian Maria , Kucukalic Abdulah , Lecic-Tosevski Dusica , Morina Nexhmedin , Popovski Mihajlo , Schützwohl Matthias , Bogic Marija
Published: November 2012

Background/Aims: War experiences can affect mental health, but large-scale studies on the long-term impact are rare. We aimed to assess long-term mental health consequences of war in both people who stayed in the conflict area and refugees. Method: On average 8 years after the war in former Yugoslavia, participants were recruited by probabilistic sampling in 5 Balkan countries and by registers and networking in 3 Western European countries. General psychological symptoms were assessed on the Brief Symptom Inventory and posttraumatic stress symptoms on the Impact of Event Scale-Revised. Results: We assessed 3,313 interviewees in the Balkans and 854 refugees. Paranoid ideation and anxiety were the severest psychological symptoms in both samples. In multivariable regressions, older age, various specific war experiences and more traumatic experiences after the war were all associated with higher levels of both general psychological and posttraumatic stress symptoms in both samples. Additionally, a greater number of migration stressors and having only temporary legal status in the host country were associated with greater severity of symptoms in refugees. Conclusions: Psychological symptoms remain high in war-affected populations many years after the war, and this is particularly evident for refugees. Traumatic war experiences still predict higher symptom levels even when the findings have been adjusted for the influence of other factors.
Axis I and II Comorbidity and Psychosocial Functioning in Female Adolescents with Borderline Personality Disorder
Authors: Kaess Michael , von Ceumern-Lindenstjerna Ina-Alexandra , Parzer Peter , Chanen Andrew , Mundt Christoph , Resch Franz , Brunner Romuald
Published: November 2012

Background: Borderline personality disorder (BPD) is known to be associated with high rates of comorbidity and severe impairment of psychosocial functioning in adults. The aim of this study was to investigate Axis I and Axis II disorders, as well as psychosocial functioning, in a clinical sample of adolescents with BPD and to compare these with participants with mixed psychiatric diagnoses. Methods: Female adolescent patients were consecutively recruited from the child and adolescent psychiatry department of a university hospital. Axis I and Axis II diagnoses were assessed by experienced clinicians using well-established semistructured interviews, along with psychosocial functioning. Results: The final sample (87 participants) comprised 31 participants with a diagnosis of BPD and 56 participants with mixed psychiatric diagnoses. The most common comorbid disorders in the adolescent BPD sample were mood, eating, dissociative, and substance use disorders in Axis I, and cluster C personality disorders in Axis II. The BPD group showed a significantly higher average number of comorbid Axis I and Axis II diagnoses and significantly lower psychosocial functioning compared with the clinical control group. Regression analyses revealed that psychosocial functioning was predicted by socioeconomic status and comorbid disorders, as well as the unique influence of BPD itself. Conclusion: Adolescent BPD in females is accompanied by high rates of psychiatric comorbidity and poor psychosocial functioning. This underscores the need for diagnosis of BPD at its early stages, in order to facilitate appropriate interventions.
The Role of Chemoprevention of Colorectal Cancer with 5-Aminosalicylates in Ulcerative Colitis
Authors: Herfarth Hans
Published: November 2012

5-aminosalicylates (5-ASA) are widely used to treat patients with ulcerative colitis. Experimental data suggest that these agents can potentially be used in a chemopreventive fashion to inhibit the development of colitis-associated colorectal cancer (CRC); however, observational studies investigating a possible risk reduction of CRC by 5-ASA therapy have revealed conflicting results. Currently, it appears that 5-ASA have no or only a very limited effect as a deterrence against CRC. Thus, a general recommendation for long-term use of 5-ASA solely for chemopreventive measures is not warranted.
Computed Tomographic and Magnetic Resonance Colonography: Challenge for Colonoscopy
Authors: Rockey Don C.
Published: November 2012

Background: Computed tomographic (CT) and magnetic resonance (MR) colonography are new noninvasive techniques to examine the colon. Methods: A literature search was performed through 2/1/2012, and relevant studies included in the review. Results: MR colonography is evolving, and holds the promise that it may achieve high-level sensitivity for adenomas and cancers without exposure to radiation. CT colonography is much more mature at this point in time, and has received great attention in the last decade as a colon imaging tool, including potentially as a primary colon cancer screening method. Its accuracy for detection of polypoid lesions ≥1 cm is high, likely close to that of colonoscopy. New techniques focusing on minimally prepped CT colonography hold the potential of making the procedure more widely accepted. While radiation exposure with CT colonography is a concern, this risk is likely very modest, particularly if used in patients over the age of 50. CT colonography, while a viable colon cancer screening modality in the USA, could not be widely implemented, largely because of lack of standards for training and reading, and because the number of skilled readers is limited. Summary: MR and CT colonography are relatively novel and exciting modalities that can be used to identify colonic lesions. They promise a high level of sensitivity and pose essentially no (MR) or modest (CT) risks. Future investigation will likely lead to wider acceptance of both of these tests, including perhaps to their use in colon cancer screening programs.
The Transanal Endoscopic Microsurgery Procedure: Standards and Extended Indications
Authors: Léonard Daniel , Remue Christophe , Kartheuser Alex
Published: November 2012

Transanal endoscopic microsurgery (TEM) was developed in the early 1980s as a minimally invasive technique allowing the resection of benign rectal adenomas. For this indication, TEM was reported to be safe and effective and even exceeded the results compared to classical local excision. Unsurprisingly, the indication expanded to small rectal cancer. There is still much debate, though, whether it is oncologically safe to perform TEM for rectal cancer. Much has been published about the need for proper patient selection, i.e. patients presenting a low-risk T1 rectal cancer seem to be the most adequate subgroup for this technique. Nevertheless, TEM remains controversial concerning high-risk T1 rectal adenocarcinomas and deeper infiltrating tumors. Several retrospective case series and a small prospective study suggest that radiochemotherapy before local excision reduces recurrence to a level comparable with classic radical surgery (total mesorectal excision). However, these studies are collectively limited, and prospective data from larger multicenter trials are awaited. Reports about functional results after TEM have shown that the procedure has no permanent impact on anorectal function. Even if transient anal resting pressure weakening has been repeatedly described, patients do not suffer from any long-term functional sequelae. Nor do they complain of quality of life impairment.
Complete Response after Neoadjuvant Therapy in Rectal Cancer: To Operate or Not to Operate?
Authors: Dedemadi Georgia , Wexner Steven D.
Published: November 2012

Background/Aims: Evidence exists to support both surgical and nonoperative observational approaches to the management of patients with distal rectal cancer who achieve a complete response following neoadjuvant chemoradiotherapy (CRT). This article summarizes findings from key studies on management strategies for complete pathologic and clinical responders after neoadjuvant CRT for rectal cancer. Methods: A comprehensive literature review was undertaken comparing complete responders to neoadjuvant CRT who underwent surgical procedures or nonoperative observation. Results: The sensitivity and specificity of clinical assessment tools following neoadjuvant CRT are generally low. Endoscopic ultrasound and MRI are widely used for rectal cancer staging; PET/CT is applied for detecting residual cancer, although limitations exist in assessing mesorectal disease. In patients with rectal cancer who receive neoadjuvant CRT, rates of complete pathologic response vary from 5 to 44%. Rates of nodal disease in patients with complete pathologic response vary from 0 to 15%. In patients with stage 0 rectal cancer, excellent long-term oncologic results have been reported for both surgical resection and nonoperative observation; therefore, some authors consider that surgical resection may result in unnecessary morbidity. Whereas neoadjuvant CRT followed by total mesorectal excision (TME) reduces local recurrence and improves 5-year survival, TME is associated with significant morbidity and suboptimal functional results. Conclusion: Informed consent in patients with distal rectal cancer who achieve a complete response to neoadjuvant CRT must address both the potential risks of recurrence following nonoperative observation and the increased risks of postoperative morbidity and compromised function following extirpative surgery.
Predictors of Pathological Gambling Severity Taking Gender Differences into Account
Authors: González-Ortega I. , Echeburúa E. , Corral P. , Polo-López R. , Alberich S.
Published: November 2012

Background: The current study aims to identify predictors of pathological gambling (PG) severity, taking gender differences into account, in an outpatient sample of pathological gamblers seeking treatment. Methods: The sample for this study consisted of 103 subjects (51 women and 52 men) meeting current DSM-IV-TR criteria for PG. Linear and logistic regression analyses were used to examine different risk factors (gender, age, impulsivity, sensation seeking, self-esteem) and risk markers (depression, anxiety, gambling-related thoughts, substance abuse) as predictors of PG severity. Results: Impulsivity, maladjustment in everyday life and age at gambling onset were the best predictors in the overall sample. When gender differences were taken into account, duration of gambling disorder in women and depression and impulsivity in men predicted PG severity. In turn, a high degree of severity in the South Oaks Gambling Screen score was related to older age and more familiy support in women and to low self-esteem and alcohol abuse in men. Female gamblers were older than male gamblers and started gambling later in life, but became dependent on gambling more quickly than men. Conclusions: Further research should examine these data to tailor treatment to specific patients’ needs according to sex and individual characteristics.
Association of Lean and Fat Body Mass, Bone Biomarkers and Gonadal Steroids with Bone Mass during Pre- and Midpuberty
Authors: Csakvary Violetta , Erhardt Eva , Vargha Peter , Oroszlan Gyorgy , Bodecs Tamas , Torok Dora , Toldy Erzsebet , Kovacs Gabor L.
Published: November 2012

Background/Aims: The association of bone mass with body composition, bone turnover markers and gonadal steroids was examined in Hungarian children during pre- and midpuberty. Methods: Two hundred and thirty-seven 7- to 16-year-old subjects (56% girls) were investigated. Bone mineral density (BMD), fat mass and total and appendicular lean mass were estimated with dual-energy X-ray absorptiometry (Lunar Prodigy). The fat mass index and appendicular lean mass index (LMI) were calculated. Serum bone markers, parathyroid hormone, estradiol and testosterone were analyzed. Associations between variables were evaluated by multiple regression analysis. Results: During prepuberty, bone biomarkers, gonadal steroids and appendicular LMI were associated with bone mass in both genders (p < 0.05). During midpuberty, girls’ bone turnover markers were negatively associated with bone mass (p < 0.001). In prepuberty, appendicular LMI and β-crosslaps were predictors of bone mass in both genders. During midpuberty, appendicular LMI and gonadal steroids positively contributed to bone mass in both genders, while osteocalcin exerted a negative influence on total and L1–L4 spine BMD in girls and on L1–L4 BMD in boys (all p < 0.001). Conclusions: Predictors for bone development varied according to Tanner stage and gender. The most significant determinants of bone mass were appendicular LMI and estradiol.
Identification and Functional Characterization of a Large Deletion of the CYP11B1 Gene Causing an 11β-Hydroxylase Deficiency in a Chinese Pedigree
Authors: Xu Chao , Qiao Jie , Liu Wei , Jiang Xiuyun , Yan Fang , Wu Jiajun , Han Bing , Zhang Haiqing , Guan Qingbo , Gao Ling , Zhao Jiajun
Published: November 2012

Background: Steroid 11β-hydroxylase deficiency (11OHD) is the second most common cause of congenital adrenal hyperplasia. Inherited in an autosomal recessive manner, 11OHD is caused by mutations in the CYP11B1 gene. Objective: To identify the mutation causing 11OHD in a Chinese pedigree and analyze the functional consequences and phenotype associated with this mutation. Methods: A Chinese family with 11OHD was screened for mutations in the CYP11B1 gene. Mini-gene experiment was performed to mimic the natural splicing and outcome of the genetic variation. Results: Complete DNA sequencing of the CYP11B1 gene revealed a novel 449-bp homozygous deletion (g.2697del449) in the patient and a heterozygous deletion in both of the patient’s parents and sister. This mutation was predicted to lead to the skipping of part of exon 3 and all of exon 4 and inserting of part of intron 4 in the CYP11B1 mRNA. It generated a truncated protein and resulted in the complete destruction of the heme-binding domain of the enzyme. Conclusions: The novel deletion drastically affects normal protein structure and abolishes normal enzyme activity, leading to a severe phenotype of congenital adrenal hyperplasia due to 11OHD.
Oxidative Activity of Ammonium Persulfate Salt on Mast Cells and Basophils: Implication in Hairdressers’ Asthma
Authors: Pignatti Patrizia , Frossi Barbara , Pala Gianni , Negri Sara , Oman Hans , Perfetti Luca , Pucillo Carlo , Imbriani Marcello , Moscato Gianna
Published: November 2012

Background: Persulfate salts are components of bleaching powders widely used by hairdressers during hair-bleaching procedures. Hairdressers are at high risk for occupational asthma and rhinitis, and ammonium persulfate is the main etiologic agent. Objective: To explore the effects of ammonium persulfate on human albumin, mast cells, and basophils in order to evaluate a possible effect of ammonium persulfate oxidizing activity in the mechanism of ammonium persulfate-induced occupational asthma. Methods: High-performance liquid chromatography/mass spectrometry was performed on ammonium persulfate-incubated human albumin. The activation of LAD2 human mast cell and KU812 human basophil cell lines incubated with ammonium persulfate was evaluated. CD63 expression on persulfate-in-vitro-incubated blood basophils from nonexposed healthy controls (n = 31) and hairdressers with work-related respiratory symptoms (n = 29) was assessed by flow cytometry. Results: No persulfate-albumin conjugate was found. An oxidative process on tryptophan and methionine was detected. Ammonium persulfate induced reactive oxygen species (ROS) generation and the degranulation of LAD2 and KU812 cells. Human basophils from healthy controls, incubated in vitro with ammonium persulfate, showed increased CD63 expression and ROS production. In hairdressers with ammonium persulfate-caused occupational asthma (positive persulfate challenge), basophil-CD63 expression was higher than in those with a negative challenge and in healthy controls. Conclusions: Ammonium persulfate incubated with human albumin did not generate any adduct but oxidized some amino acids. This oxidizing activity induced human mast cell and basophil activation which might be crucial in the mechanism of persulfate-induced occupational asthma and rhinitis.
Critical Role of the Matricellular Protein SPARC in Mediating Erythroid Progenitor Cell Development in Zebrafish
Authors: Ceinos Rosa M. , Torres-Nuñez Eva , Chamorro Ruben , Novoa Beatriz , Figueras Antonio , Ruane Neil M. , Rotllant Josep
Published: November 2012

Sparc (osteonectin) is a multifunctional matricellular glycoprotein expressed by many differentiated cells. Members of this family mediate cell-matrix interactions rather than acting as structural components of the extracellular matrix (ECM); therefore, they can influence many remodelling events, including haematopoiesis. We have investigated the role of sparc in embryonic haematopoiesis using a morpholino antisense oligonucleotide-based knockdown approach. Knockdown of sparc function resulted in specific erythroid progenitor cell differentiation defects that were highlighted by changes in gene expression and morphology, which could be rescued by injection of sparc mRNA. Furthermore, a comparison of blood phenotypes of sparc and fgfs knockdowns with similar defects and the sparc rescue of the fgf21 blood phenotype places sparc downstream of fgf21 in the genetic network regulating haematopoiesis in zebrafish. These results establish a role for an ECM protein (Sparc) as an important regulator of embryonic haematopoiesis during early development in zebrafish.
Differential Approaches for Vaccination from Childhood to Old Age
Authors: Prelog Martina
Published: November 2012

Primary prevention strategies, such as vaccinations at the age extremes, in neonates and elderly individuals, demonstrate a challenge to health professionals and public health specialists. The aspects of the differentiation and maturation of the adaptive immune system, the functional implications of immunological immaturity or immunosenescence and its impact on vaccine immunogenicity and efficacy will be highlighted in this review. Several approaches have been undertaken to promote Th1 responses in neonates and to enhance immune functions in elderly, such as conjugation to carrier proteins, addition of adjuvants, concomitant vaccination with other vaccines, change in antigen concentrations or dose intervals or use of different administration routes. Also, early protection by maternal vaccination seems to be beneficial in neonates. However, it also appears necessary to think of other end points than antibody concentrations to assess vaccine efficacy in neonates or elderly, as also the cellular immune response may be impaired by the mechanisms of immaturity, underlying health conditions, immunosuppressive treatments or immunosenescence. Thus, lifespan vaccine programs should be implemented to all individuals on a population level not only to improve herd protection and to maintain protective antibody levels and immune memory, but also to cover all age groups, to protect unvaccinated elderly persons and to provide indirect protection for neonates and small infants.
Leisure Time Activities, Parental Monitoring and Drunkenness in Adolescents
Authors: Tomcikova Zuzana , Veselska Zuzana , Madarasova Geckova Andrea , van Dijk Jitse P. , Reijneveld Sijmen A.
Published: November 2012

Background: The aim of this cross-sectional study was to explore the association between adolescent drunkenness and participation in risky leisure time activities and parental monitoring. Methods: A sample of 3,694 Slovak elementary school students (mean age 14.5 years; 49.0% males) was assessed for drunkenness in the previous month, participation in risky leisure activities and parental monitoring. Results: Participation in risky leisure time activities increased the probability of drunkenness among adolescents, while parental monitoring decreased it. The effect did not change after adding the mother’s and father’s monitoring into the models. Conclusion: Our results imply that adolescents involved in going out with friends, having parties with friends and/or visiting sporting events every day or several times a week are at a higher risk of drunkenness, as are those less monitored by their parents. These less monitored adolescents and their parents should become a target group in prevention.
A Classification Model for Infant Cries with Hearing Impairment and Unilateral Cleft Lip and Palate
Authors: Etz Tanja , Reetz Henning , Wegener Carla
Published: November 2012

Objective: The aim of the study was to examine the acoustic features of infant cries in order to find differences between infants with normal development, hearing impairment (HI) and unilateral cleft lip and palate (UCLP). The study focused on two issues: (1) are differences in acoustic cry parameters specific of a certain pathological development, and (2) do these differences allow for a reliable classification of infant cries? Patients and Methods: In total, 128 spontaneous cries of infants up to 12 months of age were recorded. The mean values of acoustic cry parameters were statistically analyzed by one-way analysis of variance and Sheffé post hoc tests. A C5.0 decision tree was trained to classify infant cries by their acoustic parameters. Results: Significant differences in cry duration, fundamental frequency, formants 2 and 4, intensity, jitter, shimmer and harmonics-to-noise ratio were found between the groups. The C5.0 decision tree was able to predict an infant’s membership to the healthy, UCLP or HI groups with a probability of 89.2%. Conclusion: We conclude that C5.0 decision trees are suited to reliably classify healthy infants as well as infants with HI and UCLP by acoustic parameters.
Intermenstrual Pelvic Pain, Quality of Life and Mood
Authors: Grandi Giovanni , Xholli Anjeza , Ferrari Serena , Cannoletta Marianna , Volpe Annibale , Cagnacci Angelo
Published: November 2012

Background/Aims: To investigate the independent importance of different types of pelvic pain on quality of life and depressive symptoms. Methods: A cross-sectional study was performed on patients with pelvic pain. A 10-cm visual-analogue scale (VAS) was used to investigate intensity of intermenstrual pelvic pain, dysmenorrhea or deep dyspareunia. The SF-36 form and the Zung Self-Rating Scale for Depression (SDS) were used to investigate quality of life and depressive symptoms, respectively. Results: The final study group consisted of 248 patients, 175/248 (70.6%) with intermenstrual pelvic pain, 46/248 (18.5%) with dysmenorrhea and 27/248 (10.9%) with deep dyspareunia associated or not with dysmenorrhea. Mean VAS score for dysmenorrhea was higher than that for deep dyspareunia (p < 0.003) and intermenstrual pelvic pain (p < 0.0001). Women with intermenstrual pelvic pain had the worst SF-36 (p < 0.0001) and SDS (p < 0.002) scores. SF-36 was independently and inversely related to intermenstrual pelvic pain (CR -1.522; 95% CI -2.188 to -0.856; p < 0.0001), and less strongly to dysmenorrhea (CR -0.729; 95% CI -1.487 to 0.030; p = 0.06). Indeed, only the physical component summary of SF-36 was independently related to dysmenorrhea (CR -0.956; 95% CI -1.783 to -0.129; p = 0.024). The SDS score was independently related only to intermenstrual pelvic pain (CR 0.573; 95% CI 0.241-0.904; p = 0.0008). Conclusions: Patients with intermenstrual pelvic pain have the worst SF-36 and SDS scores. Intermenstrual pelvic pain seems to be more strongly associated with a reduced quality of life and depressive mood.