bluuebunny/crossref_metadata_2025 huggingface dataset:
The Interleukin-6 –174G/C Polymorphism and Prostate Cancer Risk: A Systematic Review and Meta-Analysis
Authors: Zhang Hongtuan , Xu Yong , Li Liang , Liu Ranlu , Ma Baojie
Published: April 2012

Objective: This systematic review and meta-analysis was undertaken to integrate previous findings and summarize the effect size of the association of interleukin-6 (IL-6) genetic polymorphism –174G/C with susceptibility to prostate cancer (PCa). Methods: All eligible studies of IL-6 –174G/C polymorphism and PCa risk were collected from the following electronic databases: PubMed and the Cochrane Library, with the last report up to June 1, 2011. Statistical analyses were performed by Review Manage version 5.0 and Stata 10.0. Results: A total of 7 independent studies, including 9,959 cases and 12,361 controls, were identified. When all studies were pooled, we did not detect a significant association of –174G/C polymorphism with PCa risk. When stratifying for race, similar results were obtained; evidence of a significant relation was absent in both Caucasians and the mixed population. After stratifying the studies by study types, –174G/C polymorphism was significantly associated with PCa risk when examining the contrast of CC + GC versus GG (OR = 1.44, 95% CI = 1.05–1.98, p = 0.03) in cohort studies but not in case-control studies. Conclusions: Our review suggest that –174G/C polymorphism is associated with an increased PCa risk in two cohort studies from one article. Additional well-designed studies are warranted to validate these findings.
Is Metformin Indicated as Primary Ovulation Induction Agent in Women with PCOS? A Systematic Review and Meta-Analysis
Authors: Siebert T.I. , Viola M.I. , Steyn D.W. , Kruger T.F.
Published: April 2012

Background: A recent meta-analysis has proven that metformin (M) is highly effective for ovulation induction in the clomiphene citrate (CC)-resistant patient. There is uncertainty whether M should be introduced as a primary ovulation induction agent in polycystic ovarian syndrome (PCOS). Methods: We conducted a systematic review and meta-analysis to establish if M is better when given alone or in combination with CC (CC+M) when compared with CC alone. This systematic review studied live birth delivery rate as the primary outcome. Results: We identified 14 prospective trials. Analysis of these results showed a reduction in the live birth rate in the group of patients treated only with M when compared with CC alone (OR = 0.48, 95% CI 0.31–0.73, p = 0.0006). An increase in ovulation (OR = 1.6, 95% CI 1.2–2.1, p = 0.0009) and pregnancy rate (OR = 1.3, 95% CI 1.0–1.6, p = 0.05) with CC+M when compared with CC alone was reported, but no difference was found when live birth rate was analyzed (OR = 1.1, 95% CI 0.8–1.5, p = 0.61). Conclusion: CC alone is superior to M alone regarding live birth rate and ovulation. The combination (CC+M) is superior to CC alone as a primary method for ovulation induction and to achieve pregnancy in PCOS. However, when addressing live birth rate, no statistically significant difference could be demonstrated. Because of the side effects profile and contraindications of M, we believe M should not be indicated as a primary ovulation induction agent in women with PCOS.
Disaster Preparedness in Home Health and Personal-Care Agencies: Are They Ready?
Authors: Daugherty Jill D. , Eiring Hilary , Blake Sarah , Howard David
Published: April 2012

Background: The use of home health care and personal-care agencies in the United States has increased by nearly 1,000% in less than 20 years. Despite the numerous advantages of keeping older and disabled people at home and fairly independent, new concerns have emerged about how to keep home health care and personal-care clients safe during emergencies and large-scale disasters. To date, little is known about the disaster preparedness activities of home health and personal-care agencies, including what oversight they have for their patients and what capabilities they sustain for preparing their clients for disasters. Objective: The purpose of this study was to explore the disaster preparedness policies and practices of these agencies and to identify opportunities for coordination with disaster preparedness officials. Methods: Semi-structured interviews were conducted by phone and in person with 21 home health and personal-care administrators across Georgia and Southern California. Transcripts from the interviews were analyzed for disaster preparedness themes. Results: We found that most agencies have very limited disaster plans and capabilities. Despite this, most stated either their intentions or outlined past experience which demonstrated their commitment to provide services to clients on a case-by-case basis throughout a large-scale emergency or disaster. Conclusion: The findings from our study help to contribute to the growing interest in disaster preparedness among home health and personal-care agencies and point to the fact that these agencies need assistance to properly lay out their disaster preparedness plans.
Translation of Molecular Pathways into Clinical Trials of Neuroendocrine Tumors
Authors: Pavel Marianne
Published: April 2012

Current treatment options for neuroendocrine tumors (NET) include somatostatin analogs, interferon-α, peptide receptor-targeted therapy and cytotoxic chemotherapy. Most patients undergo sequential therapies since these drugs are active only in subpopulations of patients and for a limited period of time. There is a need for novel drugs that are capable of amelioration of symptomatology (syndromic control) and/or tumor growth control. A number of diverse signaling pathways are involved in the pathogenesis of NET and tumor growth, thus many potential targets are available for drug targeting. Targeted therapies therefore represent an appropriate developmental therapeutic strategy given the multiplicity of potential targets in NET. These include but are not limited to: inhibitory or activating G protein-coupled receptors, receptor tyrosine kinases, ligands, and intracellular targets such as the mammalian target of rapamycin (mTOR). Numerous drugs that utilize single or multiple targets are currently in clinical development. Recently, two target-directed agents, the multiple tyrosine kinase inhibitor sunitinib and the mTOR inhibitor everolimus, have been approved for the treatment of progressive pancreatic NET. This review provides a broad overview of established and potential molecular targets in NET, summarizes data from phase II and III clinical trials with targeted drugs and outlines future therapeutic directions.
Frontostriatal Connectivity in Children during Working Memory and the Effects of Prenatal Methamphetamine, Alcohol, and Polydrug Exposure
Authors: Roussotte Florence F. , Rudie Jeffrey D. , Smith Lynne , O’Connor Mary J. , Bookheimer Susan Y. , Narr Katherine L. , Sowell Elizabeth R.
Published: April 2012

Various abnormalities in frontal and striatal regions have been reported in children with prenatal alcohol and/or methamphetamine exposure. In a recent fMRI study, we observed a correlation between accuracy on a working-memory task and functional activation in the putamen in children with prenatal methamphetamine and polydrug exposure. Because the putamen is part of the corticostriatal motor loop whereas the caudate is involved in the executive loop, we hypothesized that a loss of segregation between distinct corticostriatal networks may occur in these participants. The current study was designed to test this hypothesis using functional connectivity MRI. We examined 50 children ranging in age from 7 to 15, including 19 with prenatal methamphetamine exposure (15 of whom had concomitant prenatal alcohol exposure), 13 with prenatal exposure to alcohol but not methamphetamine, and 18 unexposed controls. We measured the coupling between blood oxygenation level dependent (BOLD) fluctuations during a working-memory task in four striatal seed regions and those in the rest of the brain. We found that the putamen seeds showed increased connectivity with frontal brain regions involved in executive functions while the caudate seeds showed decreased connectivity with some of these regions in both groups of exposed subjects compared to controls. These findings suggest that localized brain abnormalities resulting from prenatal exposure to alcohol and/or methamphetamine lead to a partial rewiring of corticostriatal networks. These results represent important progress in the field, and could have substantial clinical significance in helping devise more targeted treatments and remediation strategies designed to better serve the needs of this population.
Food Cues Do Not Modulate the Neuroendocrine Response to a Prolonged Fast in Healthy Men
Authors: Snel Marieke , Wijngaarden Marjolein A. , Bizino Maurice B. , van der Grond Jeroen , Teeuwisse Wouter M. , van Buchem Mark A. , Jazet Ingrid M. , Pijl Hanno
Published: April 2012

Introduction: Dietary restriction benefits health and increases lifespan in several species. Food odorants restrain the beneficial effects of dietary restriction in Drosophila melanogaster. We hypothesized that the presence of visual and odorous food stimuli during a prolonged fast modifies the neuroendocrine and metabolic response to fasting in humans. Subjects and Methods: In this randomized, crossover intervention study, healthy young men (n = 12) fasted twice for 60 h; once in the presence and once in the absence of food-related visual and odorous stimuli. At baseline and on the last morning of each intervention, an oral glucose tolerance test (OGTT) was performed. During the OGTT, blood was sampled and a functional MRI scan was made. Results: The main effects of prolonged fasting were: (1) decreased plasma thyroid stimulating hormone and triiodothyronine levels; (2) downregulation of the pituitary-gonadal axis; (3) reduced plasma glucose and insulin concentrations, but increased glucose and insulin responses to glucose ingestion; (4) altered hypothalamic blood oxygenation level-dependent (BOLD) signal in response to the glucose load (particularly during the first 20 min after ingestion); (5) increased resting energy expenditure. Exposure to food cues did not affect these parameters. Conclusion: This study shows that 60 h of fasting in young men (1) decreases the hypothalamic BOLD signal in response to glucose ingestion; (2) induces glucose intolerance; (3) increases resting energy expenditure, and (4) downregulates the pituitary-thyroid and pituitary-gonadal axes. Exposure to visual and odorous food cues did not alter these metabolic and neuroendocrine adaptations to nutrient deprivation.
Reclassification of Giant Viruses Composing a Fourth Domain of Life in the New Order Megavirales
Authors: Colson Philippe , de Lamballerie Xavier , Fournous Ghislain , Raoult Didier
Published: April 2012

Interest in giant viruses has risen sharply since 2003, following the discovery of the Mimivirus and four other protist-infecting giant viruses that are linked to the nucleocytoplasmic large DNA viruses (NCLDVs). Despite considerable heterogeneity in hosts and genome sizes, the NCLDVs have been shown to be monophyletic based on analyses of their sequences and gene repertoires and recent studies have proposed that these viruses share a common ancient ancestor and compose a fourth domain of life. In addition, several characteristics of these giant viruses contradict or do not match the criteria used for the canonical definition of viruses, and the NCLDV denomination is not completely appropriate. We propose here to define a new viral order named Megavirales.
Characterizing the Presence and Sensitivity of the P2X7 Receptor in Different Compartments of the Gut
Authors: de Campos Nathalia Enes , Marques-da-Silva Camila , Corrêa Gladys , Castelo-Branco Morgana Teixeira Lima , de Souza Heitor Siffert Pereira , Coutinho-Silva Robson
Published: April 2012

Purinergic signaling has been established as an important feature of inflammation and homeostasis. The expression of a number of P2 receptor subtypes in the gut has been reported. In this study, using a well-known permeabilization method that is assessed by flow cytometry, we show that lymphocytes and macrophages from the mesenteric lymph nodes (MLN) and the peritoneal cavity exhibit different sensitivities to extracellular ATP. Compared with the macrophages, the lymphocytes are more sensitive to ATP in the MLN compartment, whereas in the peritoneal cavity the macrophages are more sensitive to ATP than the lymphocytes. In addition, we have shown that the epithelial cells from the small bowel are more resistant to the ATP effects than the cells from the colon. These cells, however, become susceptible after exposure to IFN-γ. Furthermore, by examining parameters such as pH manipulation, the exposure to divalent cations and the P2X7 antagonist Brilliant Blue G, and the use of cells from P2X7–/– mice, we have shown that the P2X7 receptors are the ATP-activated receptors responsible for the permeabilization phenomenon. In addition, using Western blot analysis, we have demonstrated the changes in the P2X7 receptor expression in immune cells isolated from different sites in the gut and in the gut-associated lymphoid tissues. Our findings suggest the existence of the site-specific modulation of P2X7 receptors on epithelial and immune cells, and we define purinergic signaling as a new regulatory element in the control of inflammation and cell fate in the gut and in the gut-associated lymphoid tissues.
Tissue Microenvironments Define and Get Reinforced by Macrophage Phenotypes in Homeostasis or during Inflammation, Repair and Fibrosis
Authors: Weidenbusch Marc , Anders Hans-Joachim
Published: April 2012

Current macrophage phenotype classifications are based on distinct in vitro culture conditions that do not adequately mirror complex tissue environments. In vivo monocyte progenitors populate all tissues for immune surveillance which supports the maintenance of homeostasis as well as regaining homeostasis after injury. Here we propose to classify macrophage phenotypes according to prototypical tissue environments, e.g. as they occur during homeostasis as well as during the different phases of (dermal) wound healing. In tissue necrosis and/or infection, damage- and/or pathogen-associated molecular patterns induce proinflammatory macrophages by Toll-like receptors or inflammasomes. Such classically activated macrophages contribute to further tissue inflammation and damage. Apoptotic cells and an- tiinflammatory cytokines dominate in postinflammatory tissues which induce macrophages to produce more anti-inflammatory mediators. Similarly, tumor-associated macrophages also confer immunosuppression in tumor stroma. Insufficient parenchymal healing despite abundant growth factors pushes macrophages to gain a profibrotic phenotype and promote fibrocyte recruitment which both enforce tissue scarring. Ischemic scars are largely devoid of cytokines and growth factors so that fibrolytic macrophages that predominantly secrete proteases digest the excess extracellular matrix. Together, macrophages stabilize their surrounding tissue microenvironments by adapting different phenotypes as feed-forward mechanisms to maintain tissue homeostasis or regain it following injury. Furthermore, macrophage heterogeneity in healthy or injured tissues mirrors spatial and temporal differences in microenvironments during the various stages of tissue injury and repair.
Age-Related Changes in Spectral Transmittance of the Human Crystalline Lens in situ
Authors: Sakanishi Yoshihito , Awano Masakazu , Mizota Atsushi , Tanaka Minoru , Murakami Akira , Ohnuma Kazuhiko
Published: April 2012

Aims: It was the aim of this study to measure spectral transmission of the human crystalline lens in situ. Method: The crystalline lens was illuminated by one of four light-emitting diodes of different colors. The relative spectral transmittance of the human crystalline lens was measured with the Purkinje-Sanson mirror images over a wide range of ages. Result: The study evaluated 36 crystalline lenses of 28 subjects aged 21–76 years. There was a significant correlation between the age and spectral transmittance for blue light. Conclusion: Spectral transmittance of the crystalline lens in situ could be measured with Purkinje-Sanson mirror images.
Self-Reported Oral Hygiene Habits among Dental Patients in Italy
Authors: Villa Alessandro , Kreimer Aimee R. , Polimeni Antonella , Cicciù Domenico , Strohmenger Laura , Gherlone Enrico , Abati Silvio
Published: April 2012

Objective: The objective of this survey was to assess oral hygiene habits and compliance with guidelines for good oral health set forth by the Italian Ministry of Health (IMH). Subjects and Methods: A sample of 2,200 self-administered questionnaires was sent to four dental clinics across Italy to assess sociodemographic information, oral hygiene habits, frequency of dental visits and services received at previous visits among a population of adult patients. Results: Of the 2,200 questionnaires, 1,201 (54.6%) were returned. Findings showed that full compliance with the IMH recommendations was low (12%): a small number of patients (n = 223, 18.6%) visited a dentist every 6 months and only 256 (23.5%) brushed their teeth at least twice a day. Conclusion: Our data showed that regular attendance (at least 1 visit/year) at dental clinics for routine check-up and brushing teeth at least twice a day were poor. Therefore, we recommend that clinicians educate and motivate their patients about the benefits of healthy oral hygiene practices.
Allergen and Ozone Exacerbate Serotonin-Induced Increases in Airway Smooth Muscle Contraction in a Model of Childhood Asthma
Authors: Moore Brian D. , Hyde Dallas , Miller Lisa , Wong Emily , Frelinger Jessica , Schelegle Edward S.
Published: April 2012

Background: Serotonin (5-HT) modulates cholinergic neurotransmission and exacerbates airway smooth muscle (ASM) contraction in normal animal and nonasthmatic human tissue. Exposure to house dust mite allergen (HDMA) and ozone (O3) leads to airway hyperreactivity and 5-HT-positive cells in the airway epithelium of infant rhesus monkeys. Research shows that concomitant exposure in allergic animals has an additive effect on airway hyperreactivity. Objectives: In this study, the hypothesis is that the exposure of allergic infant rhesus monkeys to HDMA, O3 and in combination, acting through 5-HT receptors, enhances 5-HT modulation of postganglionic cholinergic ASM contraction. Methods: Twenty-four HDMA-sensitized infant monkeys were split into 4 groups at the age of 1 month, and were exposed to filtered air (FA), HDMA, O3 or in combination (HDMA+O3). At the age of 6 months, airway rings were harvested and postganglionic, and parasympathetic-mediated ASM contraction was evaluated using electrical-field stimulation (EFS). Results: 5-HT exacerbated the EFS response within all exposure groups, but had no effect in the FA group. 5-HT2, 5-HT3 and 5-HT4 receptor agonists exacerbated the response. 5-HT concentration-response curves performed after incubation with specific receptor antagonists confirmed the involvement of 5-HT2, 5-HT3 and 5-HT4 receptors. Conversely, a 5-HT1 receptor agonist attenuated the tension across all groups during EFS, and in ASM contracted via exogenous acetylcholine. Conclusions: HDMA, O3 and HDMA+O3 exposure in a model of childhood allergic asthma enhances 5-HT exacerbation of EFS-induced ASM contraction through 5-HT2, 5-HT3 and 5-HT4 receptors. A nonneurogenic inhibitory pathway exists, unaffected by exposure, mediated by 5-HT1 receptors located on ASM.
Prospective Study of Foveal Thickness Alterations after Cataract Surgery Assessed by Optical Coherence Tomography
Authors: Tsilimbaris Miltiadis , Diakonis Vasilios F. , Kymionis George D. , Eleftheriadou Maria I. , Fragkiskou Sofia , Moschandreas Joanna , Frueh Beatrice E. , Epstein Daniel , Pallikaris Aristophanis I.
Published: April 2012

Background/Aims: To evaluate the alterations of mean foveal thickness (MFT) and visual acuity (VA) outcomes after uncomplicated cataract surgery in different groups of patients. Methods: This study included eyes of consecutive patients who underwent cataract surgery between November 2007 and June 2009. The patients included in the study were divided into 4 groups, as follows: history-free patients, patients with diabetes mellitus without macular involvement at baseline, patients with glaucoma, and patients with epiretinal membrane (ERM). Preoperatively and at 1, 3 and 6 months postoperatively, patients were evaluated for MFT by optical coherence tomography at the central 1-mm macular zone and for logarithm of the minimum angle of resolution best spectacle-corrected VA (BSCVA). Results: A total of 202 eyes were included in the study. MFT values demonstrated a statistically significant increase (p < 0.01) after cataract surgery in all groups at the first and third postoperative month. The history-free (p = 0.09) and glaucoma (p = 0.19) groups did not demonstrate a statistically significant difference in MFT values between the preoperative and 6-month measurements. MFT values 6 months after cataract surgery in the diabetes and ERM groups remained significantly higher (p < 0.01). Despite these findings, VA increased significantly (p < 0.01) in all groups at all postoperative follow-ups. Conclusions: MFT values increased significantly in all groups at the first and third months after cataract surgery. At 6 months, MFT values returned to preoperative levels in the history-free and glaucoma patients, while they remained significantly higher in the diabetic and ERM patients. Despite these macular alterations, BSCVA improved significantly after cataract surgery in all groups at all postoperative follow-ups.
Dendritic Cell-Derived Tumor Necrosis Factor α Modifies Airway Epithelial Cell Responses
Authors: Lutfi R. , Ledford J.R. , Zhou P. , Lewkowich I.P. , Page K.
Published: April 2012

Mucosal dendritic cells (DC) are intimately associated with the airway epithelium and thus are ideally situated to be first responders to pathogens. We hypothesize that DC drive innate immune responses through early release of tumor necrosis factor (TNF) α, which drives airway epithelial cell responses. In a mouse model, TNFα release was significantly increased following a single exposure to German cockroach (GC) frass, an event independent of neutrophil recruitment into the airways. While lung epithelial cells and alveolar macrophages failed to release TNFα following GC frass exposure, bone marrow-derived DC (BMDC) produced substantial amounts of TNFα suggesting their importance as early responding cells. This was confirmed by flow cytometry of pulmonary myeloid DC. Addition of GC frass-pulsed BMDC or conditioned media from GC frass-pulsed BMDC to primary mouse tracheal epithelial cells (MTEC) or MLE-15 cells induced chemokine (C-C) motif ligand (CCL) 20 and granulocyte macrophage (GM) colony-stimulating factor (CSF), both of which are important for DC recruitment, survival and differentiation. Importantly, DC do not produce CCL20 or GM-CSF following allergen exposure. Blocking TNFα receptor 1 (TNFR1) completely abolished chemokine production, suggesting that BMDC-derived TNFα induced airway epithelial cell activation and enhancement of the innate immune response. Lastly, blocking TNFR1 in vivo resulted in significantly decreased CCL20 and GM-CSF production in the lungs of mice. Together, our data strongly suggest that DC-derived TNFα plays a crucial role in the initiation of innate immune responses through the modification of airway epithelial cell responses.
The Relaxant Effect of Ginseng Saponin on the Bladder and Prostatic Urethra: An in vitro and in vivo Study
Authors: Jang H.A. , Cho S. , Kang S.G. , Ko Y.H. , Kang S.H. , Bae J.H. , Cheon J. , Kim J.J. , Lee J.G.
Published: April 2012

Aim: To assess the effects of ginseng saponin on relaxation of the bladder and prostatic urethra and to determine its mechanism of action. Materials and Methods: For the in vitro study, prostatic urethra muscle strips were harvested from 18 male New Zealand rabbits. The strips were mounted in organ baths and connected to force displacement transducers. After stabilization, maximal tissue contractions were obtained by the application of phenylepinephrine to the urethra strips, and a dose-response curve for ginseng saponin was constructed (10–6–10–2M). After pretreatment of urethra strips with N-nitro-L-arginine methyl ester (L-NAME), another dose-response curve for ginseng saponin was constructed. For the in vivo study, we used adult male Sprague-Dawley rats divided into three groups [control, partial bladder outlet obstruction (PBOO) and saponin-fed groups], and we monitored the vesical pressure (Pves) and urethral perfusion pressure (UPP). Results: The ginseng saponin induced a significant dose-dependent relaxant effect on the prostatic urethra strips. A significant relaxant effect of ginseng saponin was observed from 10–3M, and ginseng saponin significantly relaxed urethra strips by 50.2 ± 20.26% at 10–2M. The relaxant effect was partially inhibited with L-NAME pretreatment. In the in vivo study, the change in UPP between baseline and relaxation was significantly higher in the saponin group than in the control or PBOO group (p < 0.001). The saponin group showed a significantly lower baseline Pves than the PBOO group. Conclusions: We observed a significant relaxation effect of ginseng saponin on the bladder and prostatic urethra in both in vitro and in vivo studies. The mechanism by which ginseng saponin induces relaxation appears to involve the nitric oxide/nitric oxide synthase pathway.
Treatment of Surgical Neck Nonunions of the Humerus with Locked Plate and Autologous Fibular Strut Graft
Authors: Gao Kanda , Gao Wei , Huang Jianhua , Wu Xiaoming , Wang Chuan Shun , Wang Qiugen
Published: April 2012

Objectives: To determine whether using a fixed-angle locked plate plus a fibular strut autograft to treat humeral surgical neck nonunions can result in improved union. Patients and Methods: The study cohort included 5 females and 2 males with an average age of 58.4 years (range 45–76) who presented with atrophic nonunion of the surgical neck of the humerus. All patients underwent revision surgery with locked plating plus a nonvascularized autologous fibular strut bone graft. Clinical and radiological union was documented in all patients. Results: The mean time from initial trauma to last revision surgery was 20.1 ± 12.6 months (range 12–48). The average time between revision surgery and the date of union was 6.1 months (range 5–8). The average active forward flexion was 124° (range 70–160) at final follow-up. The Constant-Murley score increased from an average of 25.7 points preoperatively to 77.7 points postoperatively (p < 0.001). The average analog scale of pain decreased from 7.57 points (range 6–10) preoperatively to 0.57 points (range 0–2) postoperatively (p < 0.001). Conclusions: Locked plate fixation and autologous fibular strut bone graft facilitated the successful treatment of humeral surgical neck nonunions.
Parental Origin of de novo Cytogenetically Balanced Reciprocal Non-Robertsonian Translocations
Authors: Höckner M. , Spreiz A. , Frühmesser A. , Tzschach A. , Dufke A. , Rittinger O. , Kalscheuer V. , Singer S. , Erdel M. , Fauth C. , Grossmann V. , Utermann G. , Zschocke J. , Kotzot D.
Published: April 2012

De novo cytogenetically balanced reciprocal non-Robertsonian translocations are rare findings in clinical cytogenetics and might be associated with an abnormal phenotype. Knowledge of the parental origin and mechanisms of formation is still limited. By microdissection of the derivative chromosomes and their normal homologs from metaphases followed by microsatellite-mediated marker analysis we identified 7 cases of paternal and 3 cases of maternal origin in a cohort of 10 patients with de novo cytogenetically balanced reciprocal non-Robertsonian translocations. Neither in the maternal nor in the paternal group of our study parental age seems to be increased. Together with the data from the literature our results confirm that the majority of de novo cytogenetically balanced reciprocal translocations are of paternal origin, but the preponderance does not appear to be as distinct as previously thought and the paternal age does not seem to be necessarily a major contributing factor.
Circulation: Arrhythmia and Electrophysiology
Editors' Picks
Authors:   The Editors
Published: April 2012

The following articles are being highlighted as part of
Circulation: Arrhythmia and Electrophysiology's
Topic Review series. This series will summarize the most important manuscripts, as selected by the editors, published in
Circulation: Arrhythmia and Electrophysiology, Circulation,
and the other
Circulation
subspecialty journals. The studies included in this article represent the most read manuscripts published on the topic of sudden death in 2010 and 2011.
Stroke
Authors:   The Editors
Published: April 2012

The following articles are being highlighted as part of
Circulation: Cardiovascular Genetics
' Topic Review series. This series will summarize the most important manuscripts, as selected by the editors, published in the
Circulation
portfolio and
Circulation: Cardiovascular Genetics
, in particular. The studies included in this article represent the most read manuscripts published on the topic of stroke in 2010 and 2011.
Cell Therapy Limits Myofibroblast Differentiation and Structural Cardiac Remodeling
Authors: Fedak Paul W.M. , Bai Liping , Turnbull Jeannine , Ngu Janet , Narine Kishan , Duff Henry J.
Published: April 2012

Background—

Experimental cell therapy attenuates maladaptive cardiac remodeling and improves heart function. Paracrine mechanisms have been proposed. The effect of cell therapy on post infarction cardiac fibroblast and extracellular matrix (ECM) regulation was examined.

Methods and Results—

Vascular smooth muscle cells (VSMC) were injected into the border zone of subacute infarcted syngeneic Fischer rat hearts and compared with medium-injected controls. Twelve weeks post injection, cell-treated hearts showed preserved ECM content and attenuated structural chamber remodeling. Myofibroblast activation (α-smooth muscle actin expression) was decreased significantly, while basic fibroblast growth factor (bFGF) expression, a known inhibitor of transforming growth factor β-1–induced fibroblast differentiation, was increased. Matrix metalloproteinase-2 expression and activation by gelatin zymography was unchanged between groups, while its endogenous inhibitor, tissue inhibitors of matrix metalloproteinase (TIMP)-2, showed both increased expression and enhanced inhibitory capacity in cell-treated hearts. To define paracrine mechanisms, in vitro effects of VSMC conditioned media on myofibroblast activation were assessed by 3-D collagen gel contraction assay. VSMC conditioned media significantly inhibited collagen contraction, while a specific bFGF inhibitor abolished this paracrine response. TIMP-2 induced collagen contraction, but the effect was suppressed in the presence of bFGF.

Conclusions—

Extracellular matrix dysregulation post myocardial infarction is improved by cell therapy. These data suggest that cell transplantation attenuates myofibroblast activation and subsequent maladaptive structural chamber remodeling through paracrine mechanisms involving bFGF and TIMP-2.
Long-Term (>10 Years) Clinical Outcomes of First-in-Human Biodegradable Poly-
l
-Lactic Acid Coronary Stents
Authors: Nishio Soji , Kosuga Kunihiko , Igaki Keiji , Okada Masaharu , Kyo Eisho , Tsuji Takafumi , Takeuchi Eiji , Inuzuka Yasutaka , Takeda Shinsaku , Hata Tatsuhiko , Takeuchi Yuzo , Kawada Yoshitaka , Harita Takeshi , Seki Junya , Akamatsu Shunji , Hasegawa Shinichi , Bruining Nico , Brugaletta Salvatore , de Winter Sebastiaan , Muramatsu Takashi , Onuma Yoshinobu , Serruys Patrick W. , Ikeguchi Shigeru
Published: April 2012

Background—

The purpose of this study was to evaluate the long-term safety of the Igaki-Tamai stent, the first-in-human fully biodegradable coronary stent made of poly-
l
-lactic acid.

Methods and Results—

Between September 1998 and April 2000, 50 patients with 63 lesions were treated electively with 84 Igaki-Tamai stents. Overall clinical follow-up (>10 years) of major adverse cardiac events and rates of scaffold thrombosis was analyzed together with the results of angiography and intravascular ultrasound. Major adverse cardiac events included all-cause death, nonfatal myocardial infarction, and target lesion revascularization/target vessel revascularization. During the overall clinical follow-up period (121±17 months), 2 patients were lost to follow-up. There were 1 cardiac death, 6 noncardiac deaths, and 4 myocardial infarctions. Survival rates free of all-cause death, cardiac death, and major adverse cardiac events at 10 years were 87%, 98%, and 50%, respectively. The cumulative rates of target lesion revascularization (target vessel revascularization) were 16% (16%) at 1 year, 18% (22%) at 5 years, and 28% (38%) at 10 years. Two definite scaffold thromboses (1 subacute, 1 very late) were recorded. The latter case was related to a sirolimus-eluting stent, which was implanted for a lesion proximal to an Igaki-Tamai stent. From the analysis of intravascular ultrasound data, the stent struts mostly disappeared within 3 years. The external elastic membrane area and stent area did not change.

Conclusion—

Acceptable major adverse cardiac events and scaffold thrombosis rates without stent recoil and vessel remodeling suggested the long-term safety of the Igaki-Tamai stent.
Competition Through Selective Inhibitory Synchrony
Authors: Rutishauser Ueli , Slotine Jean-Jacques , Douglas Rodney J.
Published: April 2012

Models of cortical neuronal circuits commonly depend on inhibitory feedback to control gain, provide signal normalization, and selectively amplify signals using winner-take-all (WTA) dynamics. Such models generally assume that excitatory and inhibitory neurons are able to interact easily because their axons and dendrites are colocalized in the same small volume. However, quantitative neuroanatomical studies of the dimensions of axonal and dendritic trees of neurons in the neocortex show that this colocalization assumption is not valid. In this letter, we describe a simple modification to the WTA circuit design that permits the effects of distributed inhibitory neurons to be coupled through synchronization, and so allows a single WTA to be distributed widely in cortical space, well beyond the arborization of any single inhibitory neuron and even across different cortical areas. We prove by nonlinear contraction analysis and demonstrate by simulation that distributed WTA subsystems combined by such inhibitory synchrony are inherently stable. We show analytically that synchronization is substantially faster than winner selection. This circuit mechanism allows networks of independent WTAs to fully or partially compete with other.
A Computational Feedforward Model Predicts Categorization of Masked Emotional Body Language for Longer, but Not for Shorter, Latencies
Authors: Stienen Bernard M. C. , Schindler Konrad , de Gelder Beatrice
Published: April 2012

Given the presence of massive feedback loops in brain networks, it is difficult to disentangle the contribution of feedforward and feedback processing to the recognition of visual stimuli, in this case, of emotional body expressions. The aim of the work presented in this letter is to shed light on how well feedforward processing explains rapid categorization of this important class of stimuli. By means of parametric masking, it may be possible to control the contribution of feedback activity in human participants. A close comparison is presented between human recognition performance and the performance of a computational neural model that exclusively modeled feedforward processing and was engineered to fulfill the computational requirements of recognition. Results show that the longer the stimulus onset asynchrony (SOA), the closer the performance of the human participants was to the values predicted by the model, with an optimum at an SOA of 100 ms. At short SOA latencies, human performance deteriorated, but the categorization of the emotional expressions was still above baseline. The data suggest that, although theoretically, feedback arising from inferotemporal cortex is likely to be blocked when the SOA is 100 ms, human participants still seem to rely on more local visual feedback processing to equal the model's performance.
Information Recall Using Relative Spike Timing in a Spiking Neural Network
Authors: Sterne Philip
Published: April 2012

We present a neural network that is capable of completing and correcting a spiking pattern given only a partial, noisy version. It operates in continuous time and represents information using the relative timing of individual spikes. The network is capable of correcting and recalling multiple patterns simultaneously. We analyze the network's performance in terms of information recall. We explore two measures of the capacity of the network: one that values the accurate recall of individual spike times and another that values only the presence or absence of complete patterns. Both measures of information are found to scale linearly in both the number of neurons and the period of the patterns, suggesting these are natural measures of network information. We show a smooth transition from encodings that provide precise spike times to flexible encodings that can encode many scenes. This makes it plausible that many diverse tasks could be learned with such an encoding.
Neural Dynamics, Bifurcations, and Firing Rates in a Quadratic Integrate-and-Fire Model with a Recovery Variable. I: Deterministic Behavior
Authors: Shlizerman Eli , Holmes Philip
Published: April 2012

We study the dynamics of a quadratic integrate-and-fire model of a single-compartment neuron with a slow recovery variable, as input current and parameters describing timescales, recovery variable, and postspike reset change. Analysis of a codimension 2 bifurcation reveals that the domain of attraction of a stable hyperpolarized rest state interacts subtly with reset parameters, which reposition the system state after spiking. We obtain explicit approximations of instantaneous firing rates for fixed values of the recovery variable, and use the averaging theorem to obtain asymptotic firing rates as a function of current and reset parameters. Along with the different phase-plane geometries, these computations provide explicit tools for the interpretation of different spiking patterns and guide parameter selection in modeling different cortical cell types.
Multinomial Bayesian Learning for Modeling Classical and Nonclassical Receptive Field Properties
Authors: Hosoya Haruo
Published: April 2012

We study the interplay of Bayesian inference and natural image learning in a hierarchical vision system, in relation to the response properties of early visual cortex. We particularly focus on a Bayesian network with multinomial variables that can represent discrete feature spaces similar to hypercolumns combining minicolumns, enforce sparsity of activation to learn efficient representations, and explain divisive normalization. We demonstrate that maximal-likelihood learning using sampling-based Bayesian inference gives rise to classical receptive field properties similar to V1 simple cells and V2 cells, while inference performed on the trained network yields nonclassical context-dependent response properties such as cross-orientation suppression and filling in. Comparison with known physiological properties reveals some qualitative and quantitative similarities.
Learning Where to Attend with Deep Architectures for Image Tracking
Authors: Denil Misha , Bazzani Loris , Larochelle Hugo , de Freitas Nando
Published: April 2012

We discuss an attentional model for simultaneous object tracking and recognition that is driven by gaze data. Motivated by theories of perception, the model consists of two interacting pathways, identity and control, intended to mirror the what and where pathways in neuroscience models. The identity pathway models object appearance and performs classification using deep (factored)-restricted Boltzmann machines. At each point in time, the observations consist of foveated images, with decaying resolution toward the periphery of the gaze. The control pathway models the location, orientation, scale, and speed of the attended object. The posterior distribution of these states is estimated with particle filtering. Deeper in the control pathway, we encounter an attentional mechanism that learns to select gazes so as to minimize tracking uncertainty. Unlike in our previous work, we introduce gaze selection strategies that operate in the presence of partial information and on a continuous action space. We show that a straightforward extension of the existing approach to the partial information setting results in poor performance, and we propose an alternative method based on modeling the reward surface as a gaussian process. This approach gives good performance in the presence of partial information and allows us to expand the action space from a small, discrete set of fixation points to a continuous domain.
Chaotic Exploration and Learning of Locomotion Behaviors
Authors: Shim Yoonsik , Husbands Phil
Published: April 2012

We present a general and fully dynamic neural system, which exploits intrinsic chaotic dynamics, for the real-time goal-directed exploration and learning of the possible locomotion patterns of an articulated robot of an arbitrary morphology in an unknown environment. The controller is modeled as a network of neural oscillators that are initially coupled only through physical embodiment, and goal-directed exploration of coordinated motor patterns is achieved by chaotic search using adaptive bifurcation. The phase space of the indirectly coupled neural-body-environment system contains multiple transient or permanent self-organized dynamics, each of which is a candidate for a locomotion behavior. The adaptive bifurcation enables the system orbit to wander through various phase-coordinated states, using its intrinsic chaotic dynamics as a driving force, and stabilizes on to one of the states matching the given goal criteria. In order to improve the sustainability of useful transient patterns, sensory homeostasis has been introduced, which results in an increased diversity of motor outputs, thus achieving multiscale exploration. A rhythmic pattern discovered by this process is memorized and sustained by changing the wiring between initially disconnected oscillators using an adaptive synchronization method. Our results show that the novel neurorobotic system is able to create and learn multiple locomotion behaviors for a wide range of body configurations and physical environments and can readapt in realtime after sustaining damage.
Wind Speeds at Heights Crucial for Wind Energy: Measurements and Verification of Forecasts
Authors: Drechsel Susanne , Mayr Georg J. , Messner Jakob W. , Stauffer Reto
Published: April 2012

Wind speed measurements from one year from meteorological towers and wind turbines at heights between 20 and 250 m for various European sites are analyzed and are compared with operational short-term forecasts of the global ECMWF model. The measurement sites encompass a variety of terrain: offshore, coastal, flat, hilly, and mountainous regions, with low and high vegetation and also urban influences. The strongly differing site characteristics modulate the relative contribution of synoptic-scale and smaller-scale forcing to local wind conditions and thus the performance of the NWP model. The goal of this study was to determine the best-verifying model wind among various standard wind outputs and interpolation methods as well as to reveal its skill relative to the different site characteristics. Highest skill is reached by wind from a neighboring model level, as well as by linearly interpolated wind from neighboring model levels, whereas the frequently applied 10-m wind logarithmically extrapolated to higher elevations yields the largest errors. The logarithmically extrapolated 100-m model wind reaches the best compromise between availability and low cost for data even when the vertical resolution of the model changes. It is a good choice as input for further statistical postprocessing. The amplitude of measured, height-dependent diurnal variations is underestimated by the model. At low levels, the model wind speed is smaller than observed during the day and is higher during the night. At higher elevations, the opposite is the case.
On Imbalance Generated by Vortical Flows in a Two-Layer Spherical Boussinesq Primitive Equation Model
Authors: Mirzaei Mohammad , Mohebalhojeh Ali R. , Ahmadi-Givi Farhang
Published: April 2012

The spontaneous adjustment emission of inertia–gravity waves is investigated by examining the amount of imbalance generated during the evolution of unstable jets in an isentropic two-layer primitive equation model on the sphere. To determine the balance and thus the imbalance, potential vorticity (PV) inversion by means of the first-, second-, and third-order plain-δδ, plain-δγ, and plain-γγ balance relations, as well as the Bolin–Charney balance relations, is applied. Five sets of experiments are carried out by (i) changing the upper-layer potential temperature with a fixed initial jet speed and (ii) changing the initial jet speed with a fixed upper-layer potential temperature. For each set, the relation between the optimal measure of imbalance with the corresponding measure of balanced vortical flow is sought at the peak of instability. The minimal imbalance obtained by 1 of the above 10 PV inversion procedures is considered as the optimal.

The focus herein is on the magnitude of imbalance and its scaling with various measures of balanced flow. It is shown that for the magnitude of imbalance it is always possible to find the proper measure with an exponentially small scaling. For the imbalance-to-balance ratio, however, a power law is obtained when either the jet or the stratification is weak. The latter difference in scaling behavior of the imbalance and imbalance-to-balance ratio may be an artifact of the inevitable numerical errors whose effects are felt more strongly when the signature of vortical flow is weak.
DART/CAM: An Ensemble Data Assimilation System for CESM Atmospheric Models
Authors: Raeder Kevin , Anderson Jeffrey L. , Collins Nancy , Hoar Timothy J. , Kay Jennifer E. , Lauritzen Peter H. , Pincus Robert
Published: April 2012

The Community Atmosphere Model (CAM) has been interfaced to the Data Assimilation Research Testbed (DART), a community facility for ensemble data assimilation. This provides a large set of data assimilation tools for climate model research and development. Aspects of the interface to the Community Earth System Model (CESM) software are discussed and a variety of applications are illustrated, ranging from model development to the production of long series of analyses. CAM output is compared directly to real observations from platforms ranging from radiosondes to global positioning system satellites. Such comparisons use the temporally and spatially heterogeneous analysis error estimates available from the ensemble to provide very specific forecast quality evaluations. The ability to start forecasts from analyses, which were generated by CAM on its native grid and have no foreign model bias, contributed to the detection of a code error involving Arctic sea ice and cloud cover. The potential of parameter estimation is discussed. A CAM ensemble reanalysis has been generated for more than 15 yr. Atmospheric forcings from the reanalysis were required as input to generate an ocean ensemble reanalysis that provided initial conditions for decadal prediction experiments. The software enables rapid experimentation with differing sets of observations and state variables, and the comparison of different models against identical real observations, as illustrated by a comparison of forecasts initialized by interpolated ECMWF analyses and by DART/CAM analyses.