bluuebunny/crossref_metadata_2025 huggingface dataset:
Prenatal Diagnosis of Apert Syndrome with Cloverleaf Skull Deformity Using Ultrasound, Fetal Magnetic Resonance Imaging and Genetic Analysis
Authors: Weber Benedikt , Schwabegger Anton H. , Vodopiutz Julia , Janecke Andreas R. , Forstner Rosemarie , Steiner Horst
Published: January 2010

Apert syndrome is characterized by craniosynostosis, midfacial hypoplasia and symmetric cutaneous and bony syndactyly of the limbs. The skull is usually hyperacrobrachycephalic, whereas frank cloverleafing, as a clinically obvious trilobed skull deformity, is rarely seen in these patients. We report a rare case of Apert syndrome with cloverleaf skull deformity, prenatally diagnosed at 26weeks’ gestation in which the sonographic features of a characteristic trilobed skull, abnormal biparietal diameter and head circumference, as well as malformations of the upper and lower extremities led to the diagnosis, confirmed by prenatal fibroblast growth factor receptor type 2 mutation analysis and fetal magnetic resonance imaging. The genetic evaluation revealed a p.P253R mutation in fibroblast growth factor receptor type 2 consisting in a transversion C>G at nucleotide 758. We discuss the relevant prenatal morphologic and genetic findings of this patient and review previously published cases. Our report demonstrates the feasibility of the prenatal diagnosis of Apert syndrome with cloverleaf skull using ultrasound, fetal magnetic resonance imaging and mutation analysis, and also highlights the importance of the biparietal diameter as an early predictor of growth restriction in severe craniosynostosis cases.
Prenatal Detection of Beta-Thalassemia CD17 (A→T) Mutation by Polymerase Chain Reaction/Ligase Detection Reaction/Capillary Electrophoresis for Fetal DNA in Maternal Plasma – A Case Report
Authors: Yi Ping , Chen Zhuqin , Yu Lili , Zheng Yingru , Xie Haichang , Zheng Xiuhui , Liu Qiang , Han Jian , Li Li
Published: January 2010

Objectives: It was the aim of this study to investigate the feasibility of polymerase chain reaction (PCR)/ligase detection reaction (LDR)/capillary electrophoresis for the detection of paternally inherited fetal CD17 (A→T) mutation of β-thalassemia in maternal plasma. Methods: The target DNA in maternal plasma was amplified by PCR and the mutant signal was detected by LDR. Unique LDR products were produced and separated by capillary electrophoresis. PCR/LDR/capillary electrophoresis was applied to detect CD17 (A→T) mutation in an experimental model at different sensitivity levels and from 3 maternal plasma samples. Results: The sensitivity of PCR/LDR/capillary electrophoresis for detecting low-abundance CD17 (A→T) mutation was 1:5,000 at least. The technique was applied in maternal plasma DNA for detecting paternally inherited fetal CD17 (A→T) mutation, and the results were concordant with that of PCR/reverse dot blot of amniotic fluid cell DNA. Conclusions: PCR/LDR/capillary electrophoresis has a very high sensitivity to distinguish low-abundance single nucleotide differences and probably detects paternally inherited fetal point mutations in maternal plasma.
Ileocolonic Involvement in Behçet’s Disease: Endoscopic and Histological Evaluation
Authors: Köklü Seyfettin , Yüksel Osman , Onur İlknur , Ünverdi Selman , Bıyıkoğlu İbrahim , Akbal Erdem , Şengül Demet , Ünverdi Hatice , Ekşioğlu Meral
Published: January 2010

Background: Our aim was to document the frequency of gastrointestinal (GI) involvement of Behçet’s disease (BD) at endoscopic examination. Also, we aimed to analyze whether GI lesions were correlated with other systemic components of BD. Methods: Fifty patients with BD were enrolled in the study. Patients in whom optimal colonoscopic examination of both the colon and terminal ileum could be performed were included. An ileum biopsy was taken from all cases. Upper GI endoscopy findings, presence of genital ulcers, uveitis, dermatological lesions, pathergy test, neurological involvement and peripheral vasculitis, and laboratory findings were recorded. Thirty age- and sex-matched persons who had perfect bowel cleansing and had a macroscopically normal colon and terminal ileum at colonoscopy without any systemic diseases were enrolled as the control group. Results: Nine patients and 1 case had macroscopic ileum and colon lesions, respectively. Microscopic examination of BD patients with normal colon and terminal ileum at colonoscopy revealed 61% abnormal ileum histologies. That ratio was 30% for the control group (p < 0.001). None of the patients had any lesions suggesting BD at upper GI endoscopy. There was no correlation between macro- or microscopic GI involvement and other components of BD. Conclusions: Lower GI tract, especially ileum involvement, is frequent in BD. Most of the patients have inflammation in the ileum even in the absence of macroscopic lesions.
Overexpression of SATB1 in Laryngeal Squamous Cell Carcinoma
Authors: Zhao Xu-Dong , Ji Wen-yue , Zhang Wei , He Li-Xia , Yang Jing , Liang Hong-Jun , Wang Li-Li
Published: January 2010

Objective: To investigate the expression of special AT-rich sequence-binding protein 1 (SATB1), and the relationship between SATB1 and clinicopathological factors of laryngeal squamous cell carcinoma (LSCC). Methods: Real-time PCR, Western blot and immunohistochemistry were used to analyze 80 samples of LSCC and 25 samples of control mucosa. The relationship between SATB1 expression and clinicopathological parameters was evaluated. Results: The SATB1 mRNA expression levels in LSCC were 2.5- to 7.5-fold higher than those in control mucosa tissues (p < 0.001). SATB1 protein expression was detected in approximately 66% (53 out of 80) of the LSCC specimens, whereas it was below the detection limit in all the control mucosa specimens (p < 0.001). The SATB1 mRNA levels in positive cervical lymph nodes, in clinical stages III and IV with poor/moderate cell differentiation, were significantly higher than those in negative cervical lymph nodes in clinical stage II with high cell differentiation (p = 0.022, p = 0.005 and p = 0.006, respectively). Conclusions: SATB1 mRNA and protein levels are elevated in LSCC tissues, and their levels are correlated with clinical stages and differentiation status. The current findings suggest that SATB1 may be a useful marker for the prognosis and assessment of therapeutic effects.
Molecular Characterization of the DDX3Y Gene and Its Homologs in Cattle
Authors: Liu W.-S. , Wang A. , Yang Y. , Chang T.-C. , Landrito E. , Yasue H.
Published: January 2010

DDX3Y (also known as DBY) is a member of the DEAD box protein family, which is involved in ATP-dependent RNA unwinding, needed in a variety of cellular processes including splicing, ribosome biogenesis and RNA degradation. In the human, DDX3Y is located in the AZFa interval in the Y chromosome. Deletion of the AZFa region has been shown to disrupt spermatogenesis, causing subfertility and infertility in otherwise healthy men. Here, we report the characterization of the bovine (b) DDX3Y gene and its homologs DDX3X and PL10. We found 2 transcripts for the bDDX3Y (bDDX3Y-L and -S), which correspond to the long and short transcripts of the human DDX3Y and mouse Ddx3y gene. The 2 transcripts are identical except for a 3-bp (AGT) insertion at the position of nt 2025 and an expanded 3′UTR (nt 2155–2769) in bDDX3Y-L. The bDDX3Y-S encodes a peptide of 660 amino acids (aa), while the bDDX3Y-L encodes a peptide of 661 aa as the result of an additional serine (S) insertion at the position of aa 634. Both bDDX3Y isoforms contain the conserved DEAD-box motif. The bDDX3Y is composed of 17 exons. The homologous gene on the X chromosome, bDDX3X, is highly conserved to the Y-copy at mRNA (83%) and protein (88%) levels as well as in the genomic structure. The autosomal copy, bPL10, mapped on BTA15, is a processed pseudogene with a similarity of 88.1% to bDDX3Y and 93.7% to bDDX3X mRNA, suggesting that PL10 is a retroposon of DDX3X. RT-PCR analyses showed that bDDX3Y-L, -S, bDDX3X and bPL10 were all widely expressed with predominant expression in testis and brain. Testicular section in situ hybridization revealed that sense and anti-sense RNAs of bDDX3Y-L, -S, and bDDX3X were expressed in interstitial cells. These results together with the finding that the pseudogene bPL10 is transcriptionally active in this study provide a basis for further investigating the DDX3 gene function in spermatogenesis, male fertility and gene evolution in mammals.
Copy Number Variation and Missense Mutations of the Agouti Signaling Protein (ASIP) Gene in Goat Breeds with Different Coat Colors
Authors: Fontanesi L. , Beretti F. , Riggio V. , Gómez González E. , Dall’Olio S. , Davoli R. , Russo V. , Portolano B.
Published: January 2010

In goats, classical genetic studies reported a large number of alleles at the Agouti locus with effects on coat color and pattern distribution. From these early studies, the dominant AWt (white/tan) allele was suggested to cause the white color of the Saanen breed. Here, we sequenced the coding region of the goat ASIP gene in 6 goat breeds (Girgentana, Maltese, Derivata di Siria, Murciano-Granadina, Camosciata delle Alpi, and Saanen), with different coat colors and patterns. Five single nucleotide polymorphisms (SNPs) were identified, 3 of which caused missense mutations in conserved positions of the cysteine-rich carboxy-terminal domain of the protein (p.Ala96Gly, p.Cys126Gly, and p.Val128Gly). Allele and genotype frequencies suggested that these mutations are not associated or not completely associated with coat color in the investigated goat breeds. Moreover, genotyping and sequencing results, deviation from Hardy-Weinberg equilibrium, as well as allele copy number evaluation from semiquantitative fluorescent multiplex PCR, indicated the presence of copy number variation (CNV) in all investigated breeds. To confirm the presence of CNV and evaluate its extension, we applied a bovine-goat cross-species array comparative genome hybridization (aCGH) experiment using a custom tiling array based on bovine chromosome 13. aCGH results obtained for 8 goat DNA samples confirmed the presence of CNV affecting a region of less that 100 kb including the ASIP and AHCY genes. In Girgentana and Saanen breeds, this CNV might cause the AWt allele, as already suggested for a similar structural mutation in sheep affecting the ASIP and AHCY genes, providing evidence for a recurrent interspecies CNV. However, other mechanisms may also be involved in determining coat color in these 2 breeds.
Reversible Ductus Arteriosus Constriction due to Maternal Indomethacin after Fetal Intervention for Hypoplastic Left Heart Syndrome with Intact/Restrictive Atrial Septum
Authors: Vogel Melanie , Wilkins-Haug Louise E. , McElhinney Doff B. , Marshall Audrey C. , Benson Carol B. , Silva Virginia , Tworetzky Wayne
Published: January 2010

Objective:Fetal cardiac intervention (FCI) has been performed at our center in selected fetuses with complex congenital heart disease since 2000. Most interventions are performed in fetuses with a ductus arteriosus (DA)-dependent circulation. Indomethacin promotes closure of the DA in newborns and in fetal life, a potentially life threatening complication in fetuses with ductus-dependent congenital heart disease. Methods:We reviewed our experience with FCI with a focus on the frequency, features, and clinical course of ductal constriction. Fetuses undergoing FCI receive comprehensive pre- and postoperative cardiac and cerebral ultrasound evaluation, approximately 24 hours before and after the procedure, including imaging of DA flow and Doppler assessment of the umbilical artery and vein, ductus venosus, and, since 2004, the middle cerebral artery. Results:Among 113 fetuses that underwent FCI, 24 of which were older than 28 0/7 weeks gestation, 2 were found to have DA constriction due to indomethacin therapy within 24 hours of intervention. Both of these were 30-week fetuses with hypoplastic left heart syndrome and restrictive or intact atrial septum. The DA was stenotic by spectral and color Doppler, and middle cerebral and umbilical artery pulsatility indexes were depressed. After discontinuation of indomethacin, the Doppler indices improved or normalized. Conclusion:Close echocardiographic monitoring of fetal Doppler flow velocities is very important after fetal intervention and indomethacin treatment, as the consequences of DA constriction in a fetus with hypoplastic left heart syndrome are potentially lethal. Sonographic evaluation should include measurement of cerebral and umbilical arterial flow velocities as well as color and spectral Doppler interrogation of the DA.
Update on Procedure-Related Risks for Prenatal Diagnosis Techniques
Authors: Tabor Ann , Alfirevic Zarko
Published: January 2010

Introduction: As a consequence of the introduction of effective screening methods, the number of invasive prenatal diagnostic procedures is steadily declining. The aim of this review is to summarize the risks related to these procedures. Material and Methods: Review of the literature. Results: Data from randomised controlled trials as well as from systematic reviews and a large national registry study are consistent with a procedure-related miscarriage rate of 0.5–1.0% for amniocentesis as well as for chorionic villus sampling (CVS). In single-center studies performance may be remarkably good due to very skilled operators, but these figures cannot be used for general counselling. Amniocentesis performed prior to 15 weeks had a significantly higher miscarriage rate than CVS and mid-trimester amniocentesis, and also increased the risk of talipes equinovarus. Amniocentesis should therefore not be performed before 15 + 0 weeks’ gestation. CVS on the other hand should not be performed before 10 weeks’ gestation due to a possible increase in risk of limb reduction defects. Discussion: Experienced operators have a higher success rate and a lower complication rate. The decreasing number of prenatal invasive procedures calls for quality assurance and monitoring of operators’ performance.
Kidneys of Alb/TGF-β1 Transgenic Mice Are Deficient in Retinoic Acid and Exogenous Retinoic Acid Shows Dose-Dependent Toxicity
Authors: Xu Qihe , Hendry Bruce M. , Maden Malcolm , Lu Huiyan , Wong Yuen Fei , Rankin Alexandra C. , Noor Mazhar , Kopp Jeffrey B.
Published: January 2010

Background: Alb/TGF-β1 transgenic mice overexpress active transforming growth factor-β1 (TGF-β1) in the liver, leading to increased circulating levels of the cytokine and progressive renal fibrosis. This study was designed to explore if exogenous all-trans retinoic acid (tRA) prevents renal fibrosis in this animal model. Methods: The retinoid profile in kidney and liver of wild-type and Alb/TGF-β1 transgenic mice was examined by high-performance liquid chromatography and slow-release pellets containing different amounts of tRA were implanted subcutaneously to treat the Alb/TGF-β1 transgenic mice, starting at 1 week of age; mice were sacrificed 2 weeks later. Results: Kidneys of 3-week-old wild-type mice had abundant tRA, which was completely absent in kidneys of the transgenic mice. Low doses of tRA (6–10.7 mg/kg/day) failed to affect renal fibrosis although it tended to suppress the mRNA expression of some molecular markers of fibrosis and retinal dehydrogenase 2 (RALDH2), a gene encoding a key tRA-synthesising enzyme. These tendencies disappeared, mortality tended to increase and RALDH2 and connective tissue growth factor (CTGF) mRNAs significantly increased in the medium-dose group (12.7–18.8 mg/kg/day). High doses (20.1–27.4 mg/kg/day) showed even higher toxicity with increased renal fibrosis and significant mortality. Conclusions: Alb/TGF-β1 transgenic mice are characterised by depletion of endogenous renal tRA. Exogenous tRA dose-dependently increases mortality and kidney fibrosis, which is associated with dose-dependent regulation of renal RALDH2 and CTGF mRNA expression.
Magnesium in Chronic Kidney Disease: Challenges and Opportunities
Authors: Kanbay Mehmet , Goldsmith David , Uyar Mehtap Erkmen , Turgut Faruk , Covic Adrian
Published: January 2010

Cardiovascular disease is the leading cause of mortality and morbidity in patients with chronic kidney disease, which is partly explained by the fact that 40–70% of patients receiving dialysis have significant coronary artery disease. Recent clinical studies have shown that lower serum magnesium (Mg) levels are associated with vascular calcification and cardiovascular mortality among patients with end-stage renal disease (ESRD). On the other hand, hypermagnesemia inhibits parathyroid hormone secretion, which is considered an important independent risk factor for vascular calcification, left ventricular hypertrophy and mortality in ESRD patients. Finally, increasing evidence points towards a link between Mg and cardiovascular disease, even in subjects without chronic kidney disease. The purpose of this review was to critically review the current literature examining the effects of plasma Mg levels on cardiovascular disease and parathyroid hormone homeostasis in ESRD, and renal transplant patients.
Synthetic Surfactant Based on Analogues of SP-B and SP-C Is Superior to Single-Peptide Surfactants in Ventilated Premature Rabbits
Authors: Almlén Andreas , Walther Frans J. , Waring Alan J. , Robertson Bengt , Johansson Jan , Curstedt Tore
Published: January 2010

Background: Respiratory distress syndrome (RDS) is currently treated with surfactant preparations obtained from natural sources and attempts to develop equally active synthetic surfactants have been unsuccessful. One difference in composition is that naturally derived surfactants contain the two hydrophobic proteins SP-B and SP-C while synthetic preparations contain analogues of either SP-B or SP-C. It was recently shown that both SP-B and SP-C (or SP-C33, an SP-C analogue) are necessary to establish alveolar stability at end-expiration in a rabbit RDS model, as reflected by high lung gas volumes without application of positive end-expiratory pressure. Objectives: To study the efficacy of fully synthetic surfactants containing analogues of both SP-B and SP-C compared to surfactants with only one protein analogue. Methods: Premature newborn rabbits, treated with synthetic surfactants, were ventilated for 30 min without positive end-expiratory pressure. Tidal volumes as well as lung gas volumes at end-expiration were determined. Results: Treatment with 2% Mini-B (a short-cut version of SP-B) and 2% SP-C33, or its C-terminally truncated form SP-C30, in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol, 68:31 (w/w) resulted in median lung gas volumes of 8–9 ml/kg body weight, while animals treated with 2% Mini-B surfactant or 2% SP-C33/SP-C30 surfactant had lung gas volumes of 3–4 ml/kg, and those treated with Curosurf, a porcine surfactant, 15–17 ml/kg. In contrast, mixing SP-C33 with peptides with different distributions of positively charged and hydrophobic residues did not improve lung gas volumes. Conclusions: The data indicate that synthetic surfactants containing analogues of both SP-B and SP-C might be superior to single-peptide surfactants in the treatment of RDS.
Does Elevated Hemoglobin F Modulate the Phenotype in Hb SD-Los Angeles?
Authors: Adekile Adekunle , Mullah-Ali Ali , Akar Najwa Ali
Published: January 2010

Hemoglobin (Hb) SD-Los Angeles compound heterozygotes usually have a severe clinical course although the effect of an elevated Hb F on the clinical phenotype has not been reported previously. We describe 5 Kuwaiti children with Hb SD associated with Hb F levels >20%. They all presented with sickling-related symptoms by ≤2 years of age and have been followed for 3–15 years. All had severe clinical courses marked by varying degrees of splenic sequestration crises, acute chest syndrome, vaso-occlusive crises, osteomyelitis and avascular necrosis of the femoral head. This pattern is in contrast with the usually mild presentation in Kuwaiti Hb SS patients with elevated Hb F. It therefore appears that Hb F does not ameliorate the clinical phenotype in Hb SD-Los Angeles. The reasons for this are not quite clear.
History of Childhood Abuse Is Accompanied by Increased Dissociation in Young Mothers Five Months Postnatally
Authors: Marysko Melanie , Reck Corinna , Mattheis Volker , Finke Patricia , Resch Franz , Moehler Eva
Published: January 2010

Background: Dissociation has been recognized as a relevant factor within the context of traumatization. Since childhood maltreatment as well as child birth can be regarded as a potential trauma, this study examined dissociation in a sample of 58 young mothers with a history of abuse in comparison to a control group. Methods: All women with newborn children were contacted by mail and presented with the Childhood Trauma Questionnaire. Women who reached a cutoff for moderate or severe sexual and/or physical abuse and whose children were term babies with Apgar scores >7 were included in the study to form the index group (n = 58); the control group was formed by matching mothers with no reported experiences of physical and/or sexual abuse (n = 61). Dissociative experiences were assessed by the Scale of Dissociative Experiences (German version of the Dissociative Experiences Scale). Results: The results show that mothers with a history of physical or sexual abuse – matched for infant gender, maternal education, marital status, number of infants and birth weight – had significantly more dissociative experiences. Conclusions: Maternal history of abuse significantly increases maternal dissociative experiences, which has frequently been postulated but never empirically shown in a prospective design in a sample of young mothers. As maternal psychopathology has been found to have a profound impact on child development, specifically in the first year of life, these data are of immediate relevance for preventive efforts when targeting at-risk mother-infant dyads.
The Relationship between Excessive Internet Use and Depression: A Questionnaire-Based Study of 1,319 Young People and Adults
Authors: Morrison Catriona M. , Gore Helen
Published: January 2010

Background: There is a growing awareness of a psychiatric construct that needs to be better defined and understood: Internet addiction (IA). Recently there has been much public concern over the relationship between Internet use and negative affect. This study explored the concept of IA and examined the relationship between addictive symptoms and depression. Sampling and Methods: An online questionnaire was used to measure participants’ Internet use, the functions for which they used the Internet, and their depressive tendencies. Three scales were included: the IA Test, the Internet Function Questionnaire and the Beck Depression Inventory (BDI). 1,319 respondents completed the questionnaires, with 18 (1.2%) identified as falling in the IA category. Results: Correlational analyses were conducted across the whole data sample. In factorial analyses, the 18 IA respondents were compared to a matched group of non-addicted (NA) respondents in terms of their scores on the Function Test and the BDI. Across the whole data sample, there was a close relationship between IA tendencies and depression, such that IA respondents were more depressed; there were also significant differences between the sexes, with men showing more addictive tendencies than women. In addition, young people were significantly more likely to show addictive symptoms than were older people. There was a significant difference between the IA and the NA group in their levels of depressive symptoms, with the NA group firmly in the non-depressed range, and the IA group in the moderately-to-severely depressed range (F1, 34 = 22.35; p < 0.001). In terms of the function for which they used the Internet, the IA group engaged significantly more than the NA group in sexually gratifying websites, gaming websites and online community/chat websites. Conclusions: The concept of IA is emerging as a construct that must be taken seriously. Moreover, it is linked to depression, such that those who regard themselves as dependent on the Internet report high levels of depressive symptoms. Those who show symptoms of IA are likely to engage proportionately more than the normal population in sites that serve as a replacement for real-life socialising. Further work needs to be done on validating this relationship. Future research is needed to corroborate the existing evidence and address the nature of the relationship between IA and depression: there is comorbidity between these conditions that needs greater investigation.
Dissecting Auditory Verbal Hallucinations into Two Components: Audibility (Gedankenlautwerden) and Alienation (Thought Insertion)
Authors: Sommer Iris E. , Selten Jean-Paul , Diederen Kelly M. , Blom Jan Dirk
Published: January 2010

This study proposes a theoretical framework which dissects auditory verbal hallucinations (AVH) into 2 essential components: audibility and alienation. Audibility, the perceptual aspect of AVH, may result from a disinhibition of the auditory cortex in response to self-generated speech. In isolation, this aspect leads to audible thoughts: Gedankenlautwerden. The second component is alienation, which is the failure to recognize the content of AVH as self-generated. This failure may be related to the fact that cerebral activity associated with AVH is predominantly present in the speech production area of the right hemisphere. Since normal inner speech is derived from the left speech area, an aberrant source may lead to confusion about the origin of the language fragments. When alienation is not accompanied by audibility, it will result in the experience of thought insertion. The 2 hypothesized components are illustrated using case vignettes.
Pimecrolimus Cream 1% for the Treatment of Papulopustular Eruption Related to Epidermal Growth Factor Receptor Inhibitors: A Case Series and a Literature Review of Therapeutic Approaches
Authors: Nikolaou V. , Stratigos A. , Antoniou C. , Kiagia M. , Nikolaou C. , Katsambas A. , Syrigos K.
Published: January 2010

Background: Cutaneous side effects of epidermal growth factor receptor inhibitors (EGFRIs) are very frequent and well known. The aim of our study was to investigate the efficacy and safety of pimecrolimus 1% cream in the treatment of papulopustular eruption caused by EGFRIs and to review the relevant literature on therapeutic approaches. Methods: Twenty cancer patients being treated with EGFRIs were included in the study. Nine of the patients showed grade 1 and 11 showed grade 2 papulopustular eruption. All patients were treated with pimecrolimus 1% cream, which was applied twice daily. Patients with grade 2 eruption also received systemic minocycline 100 mg/day. Results: All patients with grade 1 eruption responded to treatment, with 4/9 experiencing complete resolution of the lesions 2 weeks after the initiation of treatment. Five out of 11 patients with grade 2 eruption had more than 50% improvement in erythema and pustules, and 1 had complete resolution of the skin lesions. Two patients did not respond to treatment but were significantly improved after substitution of pimecrolimus 1% cream with metronidazole 1% cream. No side effects were recorded. Conclusions: Our case series shows that pimecrolimus cream may be an effective and safe approach in the management of papulopustular eruption related to EGFRIs.
Prevalence of Polycystic Ovary Syndrome and Related Disorders in Mexican Women
Authors: Moran Carlos , Tena Gilberto , Moran Segundo , Ruiz Paola , Reyna Rosario , Duque Ximena
Published: January 2010

Background/Aims: Polycystic ovary syndrome (PCOS) has been found to affect 4–8% of women of reproductive age; however, in Mexican-Americans a prevalence of 12.8% has been reported. This study determines the prevalence of PCOS in a sample of Mexican women. Methods: This prospective cross-sectional study included 150 female Mexican volunteers aged 20–45 years. Menstrual cycles were recorded and hirsutism was graded. Pelvic ultrasound was performed and androgen levels were measured. PCOS was diagnosed by hyperandrogenism and/or hyperandrogenemia, and oligo-ovulation (NIH 1990 criteria), and also by 2 of 3 findings: oligo-ovulation, clinical and/or biochemical hyperandrogenism and polycystic ovaries (PCO) (Rotterdam 2003 criteria), excluding other disorders. Results: Nine of the 150 women were diagnosed with PCOS, a prevalence of 6.0% (95% CI: 1.9–10.1%), according to NIH criteria. The ultrasound morphology added one patient to give ten PCOS patients, a prevalence of 6.6% (95% CI: 2.3–10.9%) according to Rotterdam criteria. All PCOS patients presented oligo-ovulation, 9 had hirsutism and 7 of them had acne. Eight of the 10 PCOS patients had morphologic characteristics of PCO. Conclusion: The prevalence of PCOS in Mexican women is approximately 6.0%, similar to other populations, but lower than 12.8% reported in Mexican-American women.
Genomic Analysis of Two-Component Signal Transduction Proteins in Basidiomycetes
Authors: Lavín José L. , Ramírez Lucía , Ussery David W. , Pisabarro Antonio G. , Oguiza José A.
Published: January 2010

Two-component system (TCS) proteins are components of complex signal transduction pathways in fungi, and play essential roles in the regulation of several cellular functions and responses. Species of basidiomycetes have a marked variation in their specific physiological traits, morphological complexity and lifestyles. In this study, we have used the available complete genomes of basidiomycetes to carry out a thorough identification and an extensive comparative analysis of the TCS proteins in this fungal phylum. In comparison with ascomycetes, basidiomycetes exhibit an intermediate number of TCS proteins. Several TCS proteins are highly conserved among all the basidiomycetes, and other TCS proteins appear to be specific to particular species of basidiomycetes. Moreover, some species appear to have developed a unique histidine kinase group with unusual domain architecture, the Dual-histidine kinases. The presence of differential sets of TCS proteins between basidiomycete species might reflect their adaptation to diverse environmental niches.
Substrate-Dependent Regulation of Carbon Catabolism in Marine Sulfate-Reducing Desulfobacterium autotrophicum HRM2
Authors: Amann Judith , Lange Daniela , Schüler Margarete , Rabus Ralf
Published: January 2010

Desulfobacterium autotrophicum HRM2 is a metabolically versatile sulfate-reducing bacterium, capable of heterotrophic (e.g. with organic acids and alcohols) and chemolithoautotrophic growth (with H2/CO2). It employs the Wood-Ljungdahl pathway for complete oxidation of acetyl-CoA to CO2 and for CO2 fixation. Here, we investigated substrate-dependent regulation at different levels of anaerobic carbon catabolism in this bacterium. (a) Whole-cell adaptation studies indicated an inducibleutilization of short-chained alcohols, agreeing with a substrate-specific abundance increase (up to 40-fold) of alcohol dehydrogenase Adh4. Simultaneous utilization of lactate and 1-propanol was paralleled by adh4 expression and Adh4 formation, respectively. (b) Degradation of propionate generally involves methylmalonyl-CoA mutase (Sbm). Expression of sbm was upregulated during growth with 1-propanol, but not with a mixture of lactate and 1-propanol. Correspondingly, propionate was excreted during growth with this substrate mixture. (c) CO dehydrogenase, the key enzyme of the Wood-Ljungdahl pathway, is encoded by several genes (cdhC, cdh1 and cdh2) located at different genomic positions. Expression of all of these genes during heterotrophic and autotrophic growth points to a reversible operation of the Wood-Ljungdahl pathway. In summary, the different regulatory patterns displayed by Db. autotrophicum HRM2 at the tested metabolic levels point to a multi-layered regulatory network.
Dual Diagnosis Competency among Addiction Treatment Staff: Training Levels, Training Needs and the Link to Retention
Authors: Schulte S.J. , Meier P.S. , Stirling J. , Berry M.
Published: January 2010

Background: Dually diagnosed clients are described as one of the most challenging treatment populations, often leading to staff frustration, helplessness and negative attitudes. As yet it is unclear whether dual diagnosis (DD)-specific competency and therapeutic optimism among staff are related to client outcomes. Methods: The study used a 3-month follow-up design involving 124 DD clients starting treatment at 6 UK addiction services. Practitioners (n = 46) treating these clients were assessed regarding their DD specialisation levels. Cox regression analyses were performed to examine predictors of clients’ 3-month retention rates. Results: Staff reported a median of 7 years work experience with DD clients, and 80% had received co-morbidity-specific training. Practitioners provided high average ratings on both the DD competency and the therapeutic optimism scale. Nevertheless, 78% of the sample indicated additional support needs in dealing with this client group. Higher levels of DD competencies among staff predicted better client retention. Conclusion: The increased provision of support packages for practitioners is vital for improving competency levels in dealing with DD clients, which in turn may lead to improved client outcomes.
Clinical Characteristics of Patients with Peripheral Pulmonary Embolism
Authors: Cha Seung-Ick , Shin Kyung-Min , Lee Jung-Woo , Lee Jongmin , Lee Shin-Yup , Kim Chang-Ho , Park Jae-Yong , Jung Tae-Hoon
Published: January 2010

Background: The clinical relevance of emboli limited to the segmental or sub-segmental pulmonary arteries and the role of anticoagulation in patients with these conditions remains to be clarified. Objectives: To determine the clinical characteristics and treatment outcomes of peripheral pulmonary embolism (PE), and in particular, isolated sub-segmental PE (ISSPE). Methods: We reviewed the data for 334 patients who were diagnosed with a PE by computed tomographic (CT) pulmonary angiography and indirect CT venography. Results: All patients were classified into one of three groups: central (245 patients, 73.4%); segmental (67 patients, 20.1%), and sub-segmental (22 patients, 6.6%). An incidental CT finding (63.6%) was the most common presentation in the segmental and sub-segmental groups. Compared with the central group, the sub-segmental group had less frequent proximal deep venous thrombosis (14 vs. 47%, Bonferroni’s corrected p = 0.002), and greater preservation of oxygenation levels (p < 0.05) without hemodynamic instability. The recurrence of PE and deaths related to PE did not occur in the sub-segmental group, although approximately 30% of the patients did not receive anticoagulation therapy. Conclusions: Patients with ISSPE may have a more benign clinical presentation, as compared to the central type, and may follow a good clinical course without mortality or recurrence.
Immobilized Kidney 28-kDa Endostatin-Related (KES28kDa) Fragment Promotes Endothelial Cell Survival
Authors: Bellini Maria Helena , Malpighi Thiago França , Calvo Fernanda Bernardes , Miranda Adriana Regina , Spencer Patrick Jack , Cichy Milena Cristina , Simons Simone Michaela , Chudzinski Tavassi Ana Marisa , Fagundes dos Santos Marinilce , Junqueira Rodrigues Consuelo , Schor Nestor
Published: January 2010

Background/Objective: Renal ischemia-hypoxia is a leading cause of acute kidney injury (AKI). Ischemia causes extracellular matrix breakdown of the tubular basement membrane. Endostatin (ES) is the C-terminal fragment of collagen XVIII generated by proteolytic cleavage. Recent studies have demonstrated that ES expression is upregulated in ischemic kidneys. The present study aimed to characterize ES from ischemic kidneys. Methods: Ischemic renal failure was induced via 45 min of occlusion of the left renal artery and vein. After the ischemic period, blood was collected. Kidneys were harvested and used for immunohistochemical testing and protein extraction. Three-step purification was used. Soluble and immobilized purified ES were tested in cell viability and adhesion assays. Results: The soluble KES28kDa inhibited endothelial cell proliferation: 25 versus 12.5 µg (p < 0.05); 12.5 versus 3.15 µg (p < 0.05). Immobilization of KES28kDa supports endothelial cell survival over the control (p = 0.021). Human umbilical vein endothelial cells plated on immobilized KES28kDa showed an increase in membrane ruffles and stress fibers. Conclusion: These data demonstrate the local synthesis of a 28-kDa ES-related fragment following AKI and suggest its role in endothelium survival.
Learning the Dynamical System Behind Sensory Data
Authors: Lee Jaehyung , Lee Soo-Young
Published: January 2010

This letter looks at the physics behind sensory data by identifying the parameters that govern the physical system and estimating them from sensory observations. We extend Takens's delay-embedding theorem to the dynamical systems controlled by parameters. An embedding of the product space of the phase and the parameter spaces of the dynamical system can be obtained by the delay-embedding map, provided that the parameter of the dynamical system changes slowly. The reconstruction error is bounded for slowly varying parameters. A manifold learning technique is applied to the embedding obtained to extract a low-dimensional global coordinate system representing the product space. The phase space of the deterministic dynamics can be contracted by using the adjacency relationship in time, which enables recovery of only the parameter space. As examples, the manifolds of synthetic and real-world vowels with time-varying fundamental frequency (F0) are analyzed, and the F0 contours are extracted by an unsupervised algorithm. Experimental results show that the proposed method leads to robust performance under various noise conditions and rapid changes of F0 compared with the current state-of-the-art F0 estimation algorithms.
Posterior Weighted Reinforcement Learning with State Uncertainty
Authors: Larsen Tobias , Leslie David S. , Collins Edmund J. , Bogacz Rafal
Published: January 2010

Reinforcement learning models generally assume that a stimulus is presented that allows a learner to unambiguously identify the state of nature, and the reward received is drawn from a distribution that depends on that state. However, in any natural environment, the stimulus is noisy. When there is state uncertainty, it is no longer immediately obvious how to perform reinforcement learning, since the observed reward cannot be unambiguously allocated to a state of the environment. This letter addresses the problem of incorporating state uncertainty in reinforcement learning models. We show that simply ignoring the uncertainty and allocating the reward to the most likely state of the environment results in incorrect value estimates. Furthermore, using only the information that is available before observing the reward also results in incorrect estimates. We therefore introduce a new technique, posterior weighted reinforcement learning, in which the estimates of state probabilities are updated according to the observed rewards (e.g., if a learner observes a reward usually associated with a particular state, this state becomes more likely). We show analytically that this modified algorithm can converge to correct reward estimates and confirm this with numerical experiments. The algorithm is shown to be a variant of the expectation-maximization algorithm, allowing rigorous convergence analyses to be carried out. A possible neural implementation of the algorithm in the cortico-basal-ganglia-thalamic network is presented, and experimental predictions of our model are discussed.
Alteration of Ambient GABA by Phasic and Tonic Neuronal Activation
Authors: Hoshino Osamu
Published: January 2010

Neurons of primary auditory cortex (AI) emit spikes (action potentials) in two distinct manners, responding to sounds in an onset or a sustained manner. The former AI neurons are called phasic cells and the latter tonic cells. The phasic cells generate spikes for a brief time period (less than hundreds of milliseconds) at the onset of an auditory stimulus (e.g., a tone frequency sound), and the tonic cells continuously generate spikes throughout the stimulation period. Simulating a neural network model of AI, we investigated whether and how the onset discharges influence the sustained discharges that are believed to play a central role in encoding auditory information. Onset discharges, triggered by a phasic input, briefly excited GABAergic interneurons and transiently increased the level of ambient GABA, which was immediately recognized by extrasynaptic GABAa receptors and provided inhibitory currents into neurons. The transient alteration of ambient GABA allowed tonic cells to respond selectively to a tonic input. The timing of phasic input relative to a tonic one had a great impact on the responsiveness of tonic cells. We found optimal timing for the best selective responsiveness: phasic input preceding tonic input by several tens of milliseconds. Offset discharges induced by a secondary input to phasic cells, applied at the end of the tonic input period, suddenly terminated the sustained discharges and allowed the network to return rapidly to the ongoing-spontaneous neuronal state. We suggest that the transporter-mediated alteration of ambient GABA, triggered by onset discharges, may improve the response property of AI neurons. Offset discharges may have a role in resetting AI neurons so that they can prepare for the next auditory input.
Nonconvergence in Logistic and Poisson Models for Neural Spiking
Authors: Zhao Mengyuan , Iyengar Satish
Published: January 2010

Generalized linear models are an increasingly common approach for spike train data analysis. For the logistic and Poisson models, one possible difficulty is that iterative algorithms for computing parameter estimates may not converge because of certain data configurations. For the logistic model, these configurations are called complete and quasi-complete separation. We show that these features are likely to occur because of refractory periods of neurons. We use an example to study how standard software deals with this difficulty. For the Poisson model, we show that the same difficulties arise, this time possibly due to bursting or specifics of the binning. We characterize the nonconvergent configurations for both models, show that they can be detected by linear programming methods, and discuss possible remedies.
Roles of Inhibitory Neurons in Rewiring-Induced Synchronization in Pulse-Coupled Neural Networks
Authors: Kanamaru Takashi , Aihara Kazuyuki
Published: January 2010

The roles of inhibitory neurons in synchronous firing are examined in a network of excitatory and inhibitory neurons with Watts and Strogatz's rewiring. By examining the persistence of the synchronous firing that exists in the random network, it was found that there is a probability of rewiring at which a transition between the synchronous state and the asynchronous state takes place, and the dynamics of the inhibitory neurons play an important role in determining this probability.
Response of Integrate-and-Fire Neurons to Noisy Inputs Filtered by Synapses with Arbitrary Timescales: Firing Rate and Correlations
Authors: Moreno-Bote Rubén , Parga Néstor
Published: January 2010

Delivery of neurotransmitter produces on a synapse a current that flows through the membrane and gets transmitted into the soma of the neuron, where it is integrated. The decay time of the current depends on the synaptic receptor's type and ranges from a few (e.g., AMPA receptors) to a few hundred milliseconds (e.g., NMDA receptors). The role of the variety of synaptic timescales, several of them coexisting in the same neuron, is at present not understood. A prime question to answer is which is the effect of temporal filtering at different timescales of the incoming spike trains on the neuron's response. Here, based on our previous work on linear synaptic filtering, we build a general theory for the stationary firing response of integrate-and-fire (IF) neurons receiving stochastic inputs filtered by one, two, or multiple synaptic channels, each characterized by an arbitrary timescale. The formalism applies to arbitrary IF model neurons and arbitrary forms of input noise (i.e., not required to be gaussian or to have small amplitude), as well as to any form of synaptic filtering (linear or nonlinear). The theory determines with exact analytical expressions the firing rate of an IF neuron for long synaptic time constants using the adiabatic approach. The correlated spiking (cross-correlations function) of two neurons receiving common as well as independent sources of noise is also described. The theory is illustrated using leaky, quadratic, and noise-thresholded IF neurons. Although the adiabatic approach is exact when at least one of the synaptic timescales is long, it provides a good prediction of the firing rate even when the timescales of the synapses are comparable to that of the leak of the neuron; it is not required that the synaptic time constants are longer than the mean interspike intervals or that the noise has small variance. The distribution of the potential for general IF neurons is also characterized. Our results provide powerful analytical tools that can allow a quantitative description of the dynamics of neuronal networks with realistic synaptic dynamics.
Independent Vector Analysis for Source Separation Using a Mixture of Gaussians Prior
Authors: Hao Jiucang , Lee Intae , Lee Te-Won , Sejnowski Terrence J.
Published: January 2010

Convolutive mixtures of signals, which are common in acoustic environments, can be difficult to separate into their component sources. Here we present a uniform probabilistic framework to separate convolutive mixtures of acoustic signals using independent vector analysis (IVA), which is based on a joint distribution for the frequency components originating from the same source and is capable of preventing permutation disorder. Different gaussian mixture models (GMM) served as source priors, in contrast to the original IVA model, where all sources were modeled by identical multivariate Laplacian distributions. This flexible source prior enabled the IVA model to separate different type of signals. Three classes of models were derived and tested: noiseless IVA, online IVA, and noisy IVA. In the IVA model without sensor noise, the unmixing matrices were efficiently estimated by the expectation maximization (EM) algorithm. An online EM algorithm was derived for the online IVA algorithm to track the movement of the sources and separate them under nonstationary conditions. The noisy IVA model included the sensor noise and combined denoising with separation. An EM algorithm was developed that found the model parameters and separated the sources simultaneously. These algorithms were applied to separate mixtures of speech and music. Performance as measured by the signal-to-interference ratio (SIR) was substantial for all three models.