bluuebunny/crossref_metadata_2025 huggingface dataset:
Perinatal Periodontal Disease Reduces Social Behavior in Male Offspring
Authors: Pimentel S.P. , Casati M.Z. , Cirano F.R. , Ribeiro F.V. , Casarin R.V. , Kirsten T.B. , Chaves-Kirsten G.P. , Duarte P.M. , Bernardi M.M.
Published: November 2012

Objective: Our objective was to verify whether prenatal maternal periodontitis is a risk factor for the development of central nervous system disorders in rats. Methods: Periodontitis was induced by placing a ligature around the upper and lower first molars in 9 female Wistar rats (experimental group); 9 rats were left unligated (control group). The maternal general activity in an open field was observed on gestational day (GD) 0, GD 4, and GD 14, and the maternal performance was assessed on the second day after birth. The pups’ play behavior was assessed on postnatal day 30. The relative level of reelin was measured in the frontal cortex by real-time PCR analysis. Results: The results showed that, compared with the control group, (1) the general activity in female rats with periodontitis was decreased, (2) the maternal performance of these rats was not modified by periodontitis, (3) the play behavior of pups from dams with periodontitis was decreased, and (4) there were no differences in the frontal cortex reelin levels of pups from dams with periodontitis. Conclusions: We conclude that pre- and postnatal periodontitis induces maternal sickness behavior and reduces the pups’ play behavior without interference with frontal cortex reelin expression.
Phenolic Compounds and Interaction between Aminoglycosides and Natural Products of Lygodium venustum SW against Multiresistant Bacteria
Authors: Morais-Braga M.F.B. , Souza T.M. , Santos K.K.A. , Guedes G.M.M. , Andrade J.C. , Tintino S.R. , Sobral-Souza C.E. , Costa J.G.M. , Saraiva A.A.F. , Coutinho H.D.M.
Published: November 2012

Background: The aim of this work was to evaluate the interactions between aminoglycosides and the ethyl-acetate fraction of the fern Lygodium venustum SW (EAFLV) Methods: The ethyl-acetate fraction was obtained from the ethanol extract of L. venustum and was assayed via the checkerboard method associated with aminoglycosides against two bacterial strains multiresistant to antibiotics. Results: The antibiotic activity of all drugs, when associated with the ethyl-acetate fraction, was enhanced in an additive manner, except for the association between EAFLV and amikacin, which showed a synergistic interaction against the Escherichia coli strain. Conclusions: The results indicated that L. venustum can be a source of secondary metabolites to be used in association with antibiotics like aminoglycosides in antibiotic chemotherapy against resistant bacteria.
An International Survey of Deep Brain Stimulation Procedural Steps
Authors: Abosch Aviva , Timmermann Lars , Bartley Sylvia , Rietkerk Hans Guido , Whiting Donald , Connolly Patrick J. , Lanctin David , Hariz Marwan I.
Published: November 2012

Background: Deep brain stimulation (DBS) surgery is standard of care for the treatment of certain movement disorders. Objective: We sought to characterize the spectrum of steps performed in DBS surgery, at centers around the world where this surgery is performed. Methods: We identified the main steps in DBS surgery workflow and grouped these 19 steps into 3 phases (preoperative, operative, and postoperative). A survey tool, informed by a pilot survey, was administered internationally by trained study personnel at high- and low-volume DBS centers. Procedural components, duration, and surgeon motivational factors were assessed. Cluster analysis was used to identify procedural and behavioral clusters. Results: One hundred eighty-five procedure workflow surveys (143 DBS centers) and 65 online surveys of surgeon motivational drivers were completed (45% response rate). Significant heterogeneity in technique, operative time, and surgeon motivational drivers was reported across centers. Conclusions: We provide a description of the procedural steps involved in DBS surgery and the duration of these steps, based on an international survey. These data will enable individual surgeons and centers to examine their own experience relative to colleagues at other centers and in other countries. Such information could also be useful in comparing efficiencies and identifying workflow obstacles between different hospital environments.
X Chromosome-Inactivation Patterns in 31 Individuals with PHACE Syndrome
Authors: Sullivan C.T. , Christian S.L. , Shieh J.T.C. , Metry D. , Blei F. , Krol A. , Drolet B.A. , Frieden I.J. , Dobyns W.B. , Siegel D.H.
Published: November 2012

Segmental hemangiomas of the head and neck can be associated with multiple congenital anomalies in the disorder known as PHACE syndrome (OMIM 606519) (posterior fossa malformations, hemangioma, arterial anomalies, cardiac defects, and eye anomalies). All reported cases of PHACE syndrome to date have been sporadic, and the genetic basis of this disorder has not yet been established. PHACE syndrome has a striking female predominance which has raised the question of X-linked inheritance. In this study, the X chromosome-inactivation (XCI) patterns of 31 females with PHACE syndrome and their mothers were analyzed using blood-derived DNA and X-chromosome locus methylation assay. This study was performed to test the hypothesis that some cases of PHACE syndrome are due to X-linked inheritance and favorable skewing in the mothers may protect against a severe phenotype, but the clinical phenotype may be unmasked in daughters with a random pattern of X-inactivation. XCI analysis was informative in 27/31 mothers. Our results identified skewed XCI in 5 of 27 (19%) informative mothers, which is not statistically significant with a p value of 0.41. None of the mothers reported significant medical problems, although a full PHACE work-up has not been performed in these individuals. Skewed XCI in the mothers of children with PHACE was identified in only a minority of cases. Based on these results, genetic heterogeneity is likely in PHACE syndrome, although it is possible a subset of cases are caused by a mutation in an X-linked gene.
Refining the Diagnosis and Prognostic Categorization of Acute Myeloid Leukemia Patients with an Integrated Use of Cytogenetic and Molecular Studies
Authors: Costa Dolors , Vidal Anna , Carrió Ana , Muñoz Concha , Arias Amparo , Gómez Cándida , Berneaga Daniela , Colomer Dolors , Rozman Maria , Pratcorona Marta , Torrebadell Montserrat , Díaz-Beyá Marina , Esteve Jordi , Campo Elías
Published: November 2012

Significant progress in the understanding of the genetic basis of acute myeloid leukemia (AML) has been made during the last 30 years. The aim of the present study was to assess whether the detection of recurrent gene rearrangements by fluorescent in situ hybridization (FISH) studies and NPM1 and FLT3 gene mutations by molecular studies added clinically relevant information to the karyotype in 113 AML patients. Thus, FISH and molecular studies were found to add new information in 22 and 55% of the patients, respectively, particularly in cases with normal karyotype (NK) or when a cytogenetic analysis failed. Patients with NK changed their genetic risk group to favorable in 27 and 29% of cases using FISH and molecular biology studies, respectively. Our results demonstrate that molecular biology and FISH studies provide relevant information in AML and should be routinely performed.
New Evidence of Neuroprotection by Lactate after Transient Focal Cerebral Ischaemia: Extended Benefit after Intracerebroventricular Injection and Efficacy of Intravenous Administration
Authors: Berthet Carole , Castillo Ximena , Magistretti Pierre J. , Hirt Lorenz
Published: November 2012

Background: Lactate protects mice against the ischaemic damage resulting from transient middle cerebral artery occlusion (MCAO) when administered intracerebroventricularly at reperfusion, yielding smaller lesion sizes and a better neurological outcome 48 h after ischaemia. We have now tested whether the beneficial effect of lactate is long-lasting and if lactate can be administered intravenously. Methods: Male ICR-CD1 mice were subjected to 15-min suture MCAO under xylazine + ketamine anaesthesia. Na l-lactate (2 µl of 100 mmol/l) or vehicle was administered intracerebroventricularly at reperfusion. The neurological deficit was evaluated using a composite deficit score based on the neurological score, the rotarod test and the beam walking test. Mice were sacrificed at 14 days. In a second set of experiments, Na l-lactate (1 µmol/g body weight) was administered intravenously into the tail vein at reperfusion. The neurological deficit and the lesion volume were measured at 48 h. Results: Intracerebroventricularly injected lactate induced sustained neuroprotection shown by smaller neurological deficits at 7 days (median = 0, min = 0, max = 3, n = 7 vs. median = 2, min = 1, max = 4.5, n = 5, p < 0.05) and 14 days after ischaemia (median = 0, min = 0, max = 3, n = 7 vs. median = 3, min = 0.5, max = 3, n = 7, p = 0.05). Reduced tissue damage was demonstrated by attenuated hemispheric atrophy at 14 days (1.3 ± 4.0 mm3, n = 7 vs. 12.1 ± 3.8 mm3, n = 5, p < 0.05) in lactate-treated animals. Systemic intravenous lactate administration was also neuroprotective and attenuated the deficit (median = 1, min = 0, max = 2.5, n = 12) compared to vehicle treatment (median = 1.5, min = 1, max = 8, n = 12, p < 0.05) as well as the lesion volume at 48 h (13.7 ± 12.2 mm3, n = 12 vs. 29.6 ± 25.4 mm3, n = 12, p < 0.05). Conclusions: The beneficial effect of lactate is long-lasting: lactate protects the mouse brain against ischaemic damage when supplied intracerebroventricularly during reperfusion with behavioural and histological benefits persisting 2 weeks after ischaemia. Importantly, lactate also protects after systemic intravenous administration, a more suitable route of administration in a clinical emergency setting. These findings provide further steps to bring this physiological, commonly available and inexpensive neuroprotectant closer to clinical translation for stroke.
Exogenous Glutamate Modulates Porcine Retinal Development in vitro
Authors: Ghosh Fredrik , Taylor Linnéa , Arnér Karin
Published: November 2012

Embryogenesis of the retina is a complex event orchestrated by a multitude of physical and biochemical signals. To study the impact of intrinsic developmental cues, the retinal tissue can be isolated in culture which also enables modulation of normal development for other purposes, i.e. transplantation of specific neuronal cell types. In the present experiment, cell type development of immature porcine retinal tissue kept in culture was explored using specific immunohistochemical markers. Retinal explants were either kept under standard culture conditions or supplemented with glutamate and their morphology was compared with in vivo controls of corresponding age. After 15 days in vitro (DIV), E45 retinal explants displayed several signs of atypical development when compared with E60 in vivo controls. First, an accelerated photoreceptor differentiation was evident, seen in sections labeled with antibodies directed against recoverin, rhodopsin and synaptophysin. Second, apoptotic cells in the inner retina were more prevalent in the cultured retinas (TUNEL). Rod photoreceptor differentiation as well as inner retinal apoptosis was even more pronounced in glutamate-supplemented specimens in which they occurred already at 8 DIV. Müller cell, vimentin and GFAP expression was not affected in any of the cultured retinas. These results suggest that normal retinal embryogenesis is more dependent on tissue extrinsic factors than what has been deduced from previous small animal experiments. Glutamate, which has been identified as an important regulator of cell cycle exit, may also be important for photoreceptor differentiation and induction of developmental apoptosis. Insights into retinal cell type differentiation under in vitro conditions is of interest from a biological standpoint, and the possibility of modulation of this process is valuable for research directed towards cell replacement in retinal degenerative disease.
Two Thermoformable Spiral Metallic Ureteral Stents in a Patient with Ileal Conduit and Distal Stenosis of the Ureters
Authors: Al-Mahmid M. , Ahrens U. , Zimmer S. , Winand S. , Özgür E. , Engelmann U.H. , Wille S.
Published: November 2012

The insertion of two thermoformable ureteral titanium spiral stents (Memokath® 051) through ileal conduit due to bilateral ureteral stenosis distally has not been described in the English literature so far. We present the case of a young female patient with a history of ileal conduit urinary diversion due to congenital urinary bladder exstrophy, who had multiple previous surgeries and the insertion of two Memokath® ureteral stents in both ureters due to distal ureteral stenosis.
Outcomes of Ureteroscopy for Stone Disease in Pregnancy: Results from a Systematic Review of the Literature
Authors: Laing K.A. , Lam T.B.L. , McClinton S. , Cohen N.P. , Traxer O. , Somani B.K.
Published: November 2012

Introduction: Our aim was to evaluate the clinical efficacy and safety of ureteroscopy as a primary treatment for pregnant women with symptomatic ureteric stones who have failed conservative management. Materials and Methods: A systematic review of the literature from January 1990 to June 2011 was performed, including all English language articles. Outcome measures were clinical efficacy, in terms of stone clearance and need for additional procedures, and safety in terms of complications. Results: A total of 239 abstracts were screened and 15 studies were identified reporting on 116 procedures. The surgical methods of stone management employed were stone extraction with basket only (n = 55, 47%), laser fragmentation (n = 27, 23%; holmium, n = 20, pulse dye, n = 7), impact lithotripsy (n = 21, 18%), ureteroscopic lithotripsy (n = 6, 5%) and a combination of methods (n = 6, 5%). A post-operative stent was inserted in 64 of 116 procedures (55%). Complete stone clearance was seen in 100 of the 116 procedures (86%). There were 2 major complications (1 ureteral perforation and 1 case of premature uterine contraction) and 7 minor complications (5 urinary tract infections and 2 cases of post-operative pain). Conclusion: This review suggests that stone clearance using ureteroscopy is a relatively safe option in pregnancy with a high success rate.
Risk of Bleeding Complications after Preoperative Antiplatelet Withdrawal versus Continuing Antiplatelet Drugs during Transurethral Resection of the Prostate and Prostate Puncture Biopsy: A Systematic Review and Meta-Analysis
Authors: Wang Jiawu , Zhang Chengyao , Tan Guangzhong , Chen Wenkai , Yang Bo , Tan Dan
Published: November 2012

Objective: To systematically evaluate the risk of antiplatelet drugs (APs) on bleeding complications in urological surgery. Methods: Studies were sought and included in this review if they were clinical controlled trials and involved transurethral resection of the prostate (TURP) and prostate puncture biopsy (PPB), which compared preoperative AP withdrawal (control group) with continuing APs (experimental group) and revealed bleeding complications as outcomes. A literature search was conducted of the electronic databases PubMed, Ovid, ScienceDirect and Embase for studies published between 1990 and 2012. Two reviewers independently screened the studies for eligibility, evaluated the quality and extracted the data from the eligible studies, with confirmation by cross-checking. There was evidence of publication bias based on Egger’s test and funnel plot. Data were processed using Cochrane Review Manager 5.0 software. Results: Nine studies involving 3,145 cases met the inclusion criteria and were included in the meta-analysis. The baselines of patients’ characteristics were comparable in all studies. The meta-analysis results showed that no differences were found in risk of bleeding after (1) TURP (OR 1.26, 95% CI 0.80–2.00, p = 0.32) or (2) PPB (OR 0.89, 95% CI 0.45–1.76, p = 0.73). Conclusion: Preoperative APs do not raise the risk of surgical bleeding complications in prostatectomy and PPB. Because of few studies and small samples, more high-quality trials with larger samples and longer follow-ups are proposed.
The Impact of Ovarian Stimulation on the Expression of Candidate Reprogramming Genes in Mouse Preimplantation Embryos
Authors: Linke M. , May A. , Reifenberg K. , Haaf T. , Zechner U.
Published: November 2012

Ovarian stimulation with gonadotrophins is an integral part of assisted reproductive technologies in human subfertility/infertility treatment. Recent findings have associated ovarian stimulation with the increased incidence of imprinting disorders in humans as well as defects in genome-wide methylation reprogramming and, in particular, imprinting in mice. Here, we present the first study that determined the impact of ovarian stimulation on the expression of developmentally important reprogramming genes (Apex1, Lig1, Lig3, Mbd2, Mbd3, Mbd4, and Polb) in single early mouse morula embryos (16-cell stage). Using absolute quantification of mRNA by quantitative real-time PCR, we observed an association of ovarian stimulation with a downregulation of mRNAs encoding the base excision repair proteins APEX1 and POLB as well as the 5-methyl-CpG-binding domain protein MBD3 in individual morula embryos. Whole mount immunofluorescence staining of early and late morula embryos with an antibody against APEX1 revealed individual embryos with lower protein expression levels after ovarian stimulation and a correlation of mRNA expression with protein abundance. Our data argue for a negative impact of ovarian stimulation during female gametogenesis and/or early embryo development affecting the expression of candidate reprogramming factors.
Ocular Surface Temperature Gradient Is Increased in Eyes with Bacterial Corneal Ulcers
Authors: Klamann Matthias K.J. , Maier Anna-Karina B. , Gonnermann Johannes , Klein Julian Philip , Bertelmann Eckart , Pleyer Uwe
Published: November 2012

Aims: To investigate the ocular surface temperature gradient in eyes with bacterial corneal ulcers. Methods: Prospective examination of 12 eyes with bacterial corneal ulcers (group 1) and 12 control eyes (group 2). Infrared thermal imaging (Tomey TG 1000) was used to study the temperature of the ocular surface. The mean, minimum and maximum temperature of the ocular surface and temperature course over a time period of 10 s of sustained eye opening were evaluated. Furthermore, a correlation between the overall corneal temperature and the temperature at the base of the corneal ulcers was determined. Results: A significant difference between both groups was present. Mean corneal temperature was 35.6°C ± 0.9 in group 1 and 34.8°C ± 0.8 in group 2 (p = 0.033). The temperature course over 10 s of sustained eye opening was –0.6°C ± 0.4 in group 1 and –0.3°C ± 0.2 in group 2 (p = 0.045). There was a close correlation between the mean temperature at the base of the corneal ulcer and the overall corneal temperature (r = 0.92, p < 0.001). Conclusion: Infrared thermal imaging can be used to objectively determine the increased ocular surface temperature in patients with bacterial corneal ulcers. The use of dynamic thermography may offer new options to monitor ocular surface alterations.
Prognostic Significance of a Systemic Inflammatory Response in Patients Undergoing Multimodality Therapy for Advanced Colorectal Cancer
Authors: Inoue Yasuhiro , Iwata Takashi , Okugawa Yoshinaga , Kawamoto Aya , Hiro Junichiro , Toiyama Yuji , Tanaka Koji , Uchida Keiichi , Mohri Yasuhiko , Miki Chikao , Kusunoki Masato
Published: November 2012

Objectives: The inflammation-based Glasgow Prognostic Score (GPS) is associated with outcome in a variety of cancers. This study investigated whether a modified GPS (mGPS) could predict survival in patients undergoing multimodality therapy for advanced colorectal cancer (CRC). Methods: We enrolled 245 patients with advanced CRC who received chemotherapy. The mGPS was recorded prior to first-line chemotherapy and to cytoreductive therapy including secondary surgery and/or radiofrequency ablation. The prognostic significance of the mGPS was analyzed using Kaplan-Meier, univariate, and multivariate analyses. Results: In patients who received chemotherapy alone (n = 163), the mGPS prior to chemotherapy was an independent prognostic indicator of survival [odds ratio (OR) 1.858; 95% confidence interval (CI) 1.213–2.846; p = 0.0044]. In patients who also underwent cytoreductive therapy (n = 82), the mGPS decreased after chemotherapy in 22 patients (27%) and increased in 5 (6%). In these patients, the mGPS prior to cytoreductive therapy was an independent prognostic indicator of survival (OR 3.412; 95% CI 1.198–9.720; p = 0.0216), but the mGPS prior to chemotherapy was not. Conclusions: The mGPS is an independent prognostic indicator of survival in patients undergoing multimodality therapy for advanced CRC, if recorded at a relevant time point.
Relationship between Plasma Pentraxin-3, Neutrophil-to-Lymphocyte Ratio, and Atherosclerosis in Renal Transplant Patients
Authors: Turkmen Kultigin , Erdur Fatih Mehmet , Guney Ibrahim , Ozbiner Huseyin , Toker Aysun , Gaipov Abduzhappar , Ozbek Orhan , Yeksan Mehdi , Tonbul Halil Zeki , Turk Suleyman
Published: November 2012

Background/Aims: Atherosclerosis and inflammation are the most important risk factors in the pathogenesis of cardiovascular diseases (CVD) in patients with end-stage renal disease (ESRD). Pentraxin-3 (PTX-3) was shown to predict inflammation and atherosclerosis in ESRD patients. However, the role of renal transplantation (Rtx) in terms of atherogenesis is still unclear. We aimed to investigate the relationship between PTX-3, neutrophil-to-lymphocyte ratio (NLR), and carotid intima-media thickness (CIMT) in Rtx patients and healthy controls. Methods: This was a cross-sectional study involving 29 Rtx patients (12 females, 40.1 ± 11.9 years) without overt CVD and 19 healthy subjects (9 females, 36.9 ± 8.9 years), testing the relationship between CIMT, assessed by ultrasonography, and selected biomarkers. Results: CIMT, PTX-3, and high-sensitivity C-reactive protein (hs-CRP) levels of Rtx patients were found to be significantly higher compared to healthy subjects. CIMT was positively correlated with age, creatinine, uric acid, triglyceride, PTX-3, hs-CRP, and NLR, and negatively correlated with estimated glomerular filtration rate in all participants. In Rtx patients, CIMT was positively correlated with age, BMI, serum phosphorus, low-density lipoprotein, and hs-CRP. The multivariate analysis revealed that hs-CRP was found to be an independent variable of CIMT in Rtx patients. Conclusion: Our data showed that inflammation and atherosclerosis persist in Rtx patients. Serum hs-CRP might be a useful marker to assess these parameters in this population.
Complex Regional Pain Syndrome Acceptance and the Alternative Denominations in the Medical Literature
Authors: Todorova Jasmina , Dantchev Nikolaj , Petrova Guenka
Published: November 2012

Objective: To analyze the use of the term ‘complex regional pain syndrome' in the medical literature and evaluate whether or not the traditional names ‘reflex sympathetic dystrophy' and ‘causalgia' have already been replaced with the new terms ‘complex regional pain syndrome type I' and ‘complex regional pain syndrome type II', respectively. Materials and Methods: The Scopus and PubMed databases were searched for reports written between 2001 and 2012 for the following descriptors in the titles: ‘complex regional pain syndrome', ‘complex regional pain syndrome type I', ‘complex regional pain syndrome type 1', ‘complex regional pain syndrome type II', ‘complex regional pain syndrome type 2', ‘CRPS', ‘CRPS type I', ‘CRPS type 1', ‘CRPS type II', ‘CRPS type 2', ‘reflex sympathetic dystrophy', ‘algodystrophy', ‘algoneurodystrophy', ‘causalgia', ‘transient osteoporosis', ‘Sudeck', and ‘shoulder-hand syndrome'. Results: Systematization of the 1,318 articles found yielded the following: 953 (72.31%) articles for the descriptor ‘complex regional pain syndrome' and a further 94 (7.13%) for its abbreviation ‘CRPS'; 180 (13.66%) for ‘reflex sympathetic dystrophy'; 33 (2.50%) for ‘shoulder-hand syndrome'; 29 (2.20%) for ‘algodystrophy'; 13 (0.99%) for ‘causalgia'; 13 (0.99%) for ‘Sudeck'; 2 (0.15%) for ‘algoneurodystrophy', and 1 (0.08%) for ‘transient osteoporosis'. The total number of articles using new terminology represents 1,047 (79.44%) of all articles. Conclusion: The new neutral term ‘complex regional pain syndrome' was most commonly used and will likely replace the traditional names ‘reflex sympathetic dystrophy' and ‘causalgia'. The new terminology is now widely accepted by the medical professionals who are mostly engaged in the treatment of CRPS patients, but not yet so in other medical spheres.
No Associations Found between PGBD1 and the Age of Onset in Japanese Patients Diagnosed with Sporadic Alzheimer’s Disease
Authors: Ohnuma Tohru , Nakamura Tohru , Takebayashi Yuto , Hanzawa Ryo , Kitazawa Maiko , Higashiyama Ryoko , Takeda Mayu , Thompson Katrin , Komatsu Miwa , Shimazaki Hiromi , Shibata Nobuto , Arai Heii
Published: November 2012

Background/Aims: PiggyBac transposable element derived 1 (PGBD1) encodes a molecule involved in epigenetic mechanisms that have been implicated in Alzheimer’s disease (AD), and recent genome-wide association studies and meta-analyses have indicated that a single nucleotide polymorphism (SNP), rs3800324, in PGBD1 could be associated with AD and the age of onset. However, no Japanese patients were examined in these studies. The aim of the present study was to replicate the previous finding in Japanese AD cases. Methods: We performed a case-control study (211 cases and 156 controls) to investigate the association between PGBD1 and Japanese AD using 4 tag SNPs including rs3800324. Results: Single SNP and haplotype analysis showed no association between AD and age of onset, whereas genotypic and allelic frequencies of the ε4 of apolipoprotein E (APOE) showed an association with AD as expected. Conclusion: In Japanese AD, we observed no influence of PGBD1, as either a risk factor or a modifier, even though APOE was associated with AD in this population.
Advances in Growth Factor Delivery for Therapeutic Angiogenesis
Authors: Said Somiraa S. , Pickering J. Geoffrey , Mequanint Kibret
Published: November 2012

Therapeutic angiogenesis is a new revascularization strategy involving the administration of growth factors to induce new vessel formation. The biology and delivery of angiogenic growth factors involved in vessel formation have been extensively studied but success in translating the angiogenic capacity of growth factors into benefits for vascular disease patients is still limited. This could be attributed to issues related to patient selection, growth factor delivery methods or lack of vessel maturation. Comprehensive understanding of the cellular and molecular cross-talk during the different stages of vascular development is needed for the design of efficient therapeutic strategies. The presentation of angiogenic factors either in series or in parallel using a strategy that mimics physiological events, such as concentration and spatio-temporal profiles, is an immediate requirement for functional blood vessel formation. This review provides an overview of the recent delivery strategies of angiogenic factors and discusses targeting neovascular maturation as a promising approach to induce stable and functional vessels for therapeutic angiogenesis.
Clinical, Genetic and Environmental Factors Associated with Congenital Vertebral Malformations
Authors: Giampietro P.F. , Raggio C.L. , Blank R.D. , McCarty C. , Broeckel U. , Pickart M.A.
Published: November 2012

Congenital vertebral malformations (CVM) pose a significant health problem because they can be associated with spinal deformities, such as congenital scoliosis and kyphosis, in addition to various syndromes and other congenital malformations. Additional information remains to be learned regarding the natural history of congenital scoliosis and related health problems. Although significant progress has been made in understanding the process of somite formation, which gives rise to vertebral bodies, there is a wide gap in our understanding of how genetic factors contribute to CVM development. Maternal diabetes during pregnancy most commonly contributes to the occurrence of CVM, followed by other factors such as hypoxia and anticonvulsant medications. This review highlights several emerging clinical issues related to CVM, including pulmonary and orthopedic outcome in congenital scoliosis. Recent breakthroughs in genetics related to gene and environment interactions associated with CVM development are discussed. The Klippel-Feil syndrome which is associated with cervical segmentation abnormalities is illustrated as an example in which animal models, such as the zebrafish, can be utilized to provide functional evidence of pathogenicity of identified mutations.
Epidermal Growth Factor Receptor Transactivation Is Necessary for Glucagon-Like Peptide-1 to Protect PC12 Cells from Apoptosis
Authors: Kimura Ryosuke , Okouchi Masahiro , Kato Takashi , Imaeda Kenro , Okayama Naotsuka , Asai Kiyofumi , Joh Takashi
Published: November 2012

Aim: Patients with long-standing diabetes commonly develop diabetic encephalopathy, which is characterized by cognitive impairment and dementia. To identify potential treatments for diabetic encephalopathy, we focused on the protective action of glucagon-like peptide-1 (GLP-1) against neural cell apoptosis. In this study, we evaluated whether exposure of cells to GLP-1 leads to epidermal growth factor receptor (EGFR) transactivation and signaling through the PI3K/Akt/mTOR/GCLc/redox pathway, which we previously reported. Methods: We monitored the phosphorylation of EGFR and Akt in PC12 cells exposed to MG and GLP-1 that had been first incubated in the presence or absence of various inhibitors of EGFR transactivation. Results: DAPI staining revealed that pretreatment of cells with BiPS, HB-EGF and anti-TGF-α neutralization antibodies or AG1478 abrogated the ability of GLP-1 to rescue cells from MG-induced apoptosis. We show that exposure of PC12 cells to GLP-1 induces EGFR phosphorylation and that this effect was inhibited by prior exposure of the cells to BiPS, HB-EGF and anti-TGF-α neutralization antibodies or AG1478. Interestingly, these agents also diminished the capacity of GLP-1 to protect cells from MG-induced apoptosis. Moreover, these agents reduced GLP-1-induced phosphorylation of Akt. EGF itself also protected the cells from MG-induced apoptosis and induced phosphorylation of Akt, which was inhibited by LY294002. Conclusion: The neuroprotective effects of GLP-1 against MG-induced apoptosis are mediated by EGFR transactivation, which signals through the PI3K/Akt/mTOR/GCLc/redox pathway in PC12 cells.
Scientific History and Experimental History
Authors: Roth Randolph
Published: November 2012

The promise of scientific history and scientifically informed history is more modest today than it was in the nineteenth century, when a number of intellectuals hoped to transform history into a scientific mode of inquiry that would unite the humanities, social sciences, and natural sciences, and reveal profound truths about human nature and destiny. But Edmund Russell in Evolutionary History and Jared Diamond and James A. Robinson in Natural Experiments of History demonstrate that historians can write interdisciplinary, comparative analyses using the strategies of nonexperimental natural science to search for deep patterns in human behavior and for correlates to those patterns that can lead to a better, though not infallible, understanding of historical causality.
Double-Nested Dynamical Downscaling Experiments over the Tibetan Plateau and Their Projection of Climate Change under Two RCP Scenarios
Authors: Ji Zhenming , Kang Shichang
Published: November 2012

A high-resolution regional climate model is used to simulate climate change over the Tibetan Plateau (TP). The model is driven at the grid spacing of 10 km by nesting the outputs of 50-km-resolution simulations. The results show that the models can capture the spatial and temporal distributions of the surface air temperature over the TP. The so-called double-nested method has a higher horizontal resolution and represents more spatial details. For example, the temperature simulations from the double-nested method reflect the observations better compared to the 50-km-resolution models. This is mainly due to the fact that topographical effects of complex terrains are detected better at higher resolution. Although both models can represent the basic patterns of precipitation, the simulated results are not as good as those of temperature. In the future, significant warming seems to develop over the TP under two representative concentration pathway (RCP) scenarios. Greater increases occur in December–February (DJF) compared with June–August (JJA). The increasing temperature trend is more pronounced over the Gangdese Mountains and over the Himalayas than in the central TP. The projection of precipitation shows the main increases in DJF. In JJA, it predicts decreases or slight changes in the southern TP. The comparison between RCP8.5 and RCP4.5 scenarios shows a similar spatial distributions of temperature and precipitation, whereas the respective values of RCP8.5 are enhanced compared with those under RCP4.5.
Relationship between Air–Sea Density Flux and Isopycnal Meridional Overturning Circulation in a Warming Climate
Authors: Han MyeongHee , Kamenkovich Igor , Radko Timour , Johns William E.
Published: November 2012

This study aims to explore the relationship between air–sea density flux and isopycnal meridional overturning circulation (MOC), using the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4) model projections of the twenty-first-century climate. The focus is on the semiadiabatic component of MOC beneath the mixed layer; this component is described using the concept of the push–pull mode, which represents the combined effects of the adiabatic push into the deep ocean in the Northern Hemisphere and the pull out of the deep ocean in the Southern Hemisphere. The analysis based on the GFDL Climate Model version 2.1 (CM2.1) simulation demonstrates that the push–pull mode and the actual isopycnal MOC at the equator evolve similarly in the deep layers, with their maximum transports decreasing by 4–5 Sv (1 Sv ≡ 106 m3 s−1) during years 2001–2100. In particular, the push–pull mode and actual isopycnal MOC are within approximately 10% of each other at the density layers heavier than 27.55 kg m−3, where the reduction in the MOC strength is the strongest. The decrease in the push–pull mode is caused by the direct contribution of the anomalous heat, rather than freshwater, surface fluxes. The agreement between the deep push–pull mode and MOC in the values of linear trend and variability on time scales longer than a decade suggests a largely adiabatic pole-to-pole mechanism for these changes. The robustness of the main conclusions is further explored in additional model simulations.
Strong Dynamical Modulation of the Cooling of the Polar Stratosphere Associated with the Antarctic Ozone Hole
Authors: Orr Andrew , Bracegirdle Thomas J. , Hosking J. Scott , Feng Wuhu , Roscoe Howard K. , Haigh Joanna D.
Published: November 2012

A model simulation forced by prescribed ozone depletion shows strong dynamical modulation of the springtime cooling of the polar stratosphere associated with the Antarctic ozone hole. The authors find that in late spring the anomalous radiative cooling in response to ozone depletion is almost canceled above ~100 hPa by an increase in dynamical heating. Between ~300 and ~100 hPa, however, it is enhanced by a reduction in dynamical heating, resulting in the descent of the cold anomaly down to the tropopause. In early summer increased dynamical heating dominates as the radiative cooling diminishes so that the cold anomaly associated with the delayed breakup of the stratospheric vortex is reduced. The anomalous dynamical heating is driven by changes in the Brewer–Dobson circulation arising primarily from the dissipation of resolved-scale waves. The model changes are broadly consistent with trends from reanalysis and offline diagnoses of heating rates using a radiation scheme. These results help one to understand dynamically induced change in the evolution and timing of the stratospheric vortex in recent decades and will help to enable improved simulation of the Southern Hemisphere climate.
On the Robustness of Emergent Constraints Used in Multimodel Climate Change Projections of Arctic Warming
Authors: Bracegirdle Thomas J. , Stephenson David B.
Published: November 2012

Statistical relationships between future and historical model runs in multimodel ensembles (MMEs) are increasingly exploited to make more constrained projections of climate change. However, such emergent constraints may be spurious and can arise because of shared (common) errors in a particular MME or because of overly influential models. This study assesses the robustness of emergent constraints used for Arctic warming by comparison of such constraints in ensembles generated by the two most recent Coupled Model Intercomparison Project (CMIP) experiments: CMIP3 and CMIP5. An ensemble regression approach is used to estimate emergent constraints in Arctic wintertime surface air temperature change over the twenty-first century under the Special Report on Emission Scenarios (SRES) A1B scenario in CMIP3 and the Representative Concentration Pathway (RCP) 4.5 scenario in CMIP5. To take account of different scenarios, this study focuses on polar amplification by using temperature responses at each grid point that are scaled by the global mean temperature response for each climate model. In most locations, the estimated emergent constraints are reassuringly similar in CMIP3 and CMIP5 and differences could have easily arisen from sampling variation. However, there is some indication that the emergent constraint and polar amplification is substantially larger in CMIP5 over the Sea of Okhotsk and the Bering Sea. Residual diagnostics identify one climate model in CMIP5 that has a notable influence on estimated emergent constraints over the Bering Sea and one in CMIP3 that that has a notable influence more widely along the sea ice edge and into midlatitudes over the western North Atlantic.
Writing About Patients: I. Ways of Protecting Confidentiality and Analysts' Conflicts Over Choice of Method
Authors: Kantrowitz Judy L.
Published: November 2012

Thirty American psychoanalysts who have published articles using clinical material from their patients were interviewed about their method for ensuring confidentiality. Almost twice as many analysts chose to disguise material (15) as regularly requested permission for the use of patients' material (8). The other analysts in the sample varied their approach, depending on circumstances, between using disguise alone and using disguise but also requesting consent. Methods of disguise, the timing of request for permission in relation to the phase of analysis, and changes in analysts' ideas about the benefits and detrimental effects of these choices are discussed and illustrated. Each decision is reconsidered in light of its potential effect on patients and their analysis. The dilemma posed by the importance of writing about patients for the health and growth of psychoanalysis as a field and the potential negative consequences for patients and their analyses is considered.
Insight, Working Through, and Practice: The Role of Procedural Knowledge
Authors: Rosenblatt Allan
Published: November 2012

A conception of insight is proposed, based on a systems and information-processing framework and using current neuroscience concepts, as an integration of information that results in a new symbolization of experience with a significant change in self-image and a transformation of nondeclarative procedural knowledge into declarative knowledge. Since procedural memory and knowledge, seen to include emotional and relationship issues, is slow to change, durable emotional and behavioral change often requires repeated practice, a need not explicitly addressed in standard psychoanalytic technique. Working through is thus seen as also encompassing nondynamic factors. The application of these ideas to therapeutic technique suggests possible therapeutic interventions beyond interpretation. An illustrative clinical vignette is presented.
Separation-Individuation Theory and Attachment Theory
Authors: Blum Harold P.
Published: November 2012

Separation-individuation and attachment theories are compared and assessed in the context of psychoanalytic developmental theory and their application to clinical work. As introduced by Margaret Mahler and John Bowlby, respectively, both theories were initially regarded as diverging from traditional views. Separation-individuation theory, though it has had to be corrected in important respects, and attachment theory, despite certain limitations, have nonetheless enriched psychoanalytic thought. Without attachment an infant would die, and with severely insecure attachment is at greater risk for serious disorders. Development depends on continued attachment to a responsive and responsible caregiver. Continued attachment to the primary object was regarded by Mahler as as intrinsic to the process of separation-individuation. Attachment theory does not account for the essential development of separateness, and separation-individuation is important for the promotion of autonomy, independence, and identity. Salient historical and theoretical issues are addressed, including the renewed interest in attachment theory and the related decline of interest in separation-individuation theory.
Another Look At Dreaming: Disentangling Freud's Primary and Secondary Process Theories
Authors: Robbins Michael
Published: November 2012

The Interpretation of Dreams contains Freud's first and most complete articulation of the primary and secondary mental processes that serve as a framework for the workings of mind, conscious and unconscious. While it is generally believed that Freud proposed a single theory of dreaming, based on the primary process, a number of ambiguities, inconsistencies, and contradictions reflect an incomplete differentiation of the parts played by the two mental processes in dreaming. It is proposed that two radically different hypotheses about dreaming are embedded in Freud's work. The one implicit in classical dream interpretation is based on the assumption that dreams, like waking language, are representational, and are made up of symbols connected to latent unconscious thoughts. Whereas the symbols that constitute waking language are largely verbal and only partly unconscious, those that constitute dreams are presumably more thoroughly disguised and represented as arcane hallucinated hieroglyphs. From this perspective, both the language of the dream and that of waking life are secondary process manifestations. Interpretation of the dream using the secondary process model involves the assumption of a linear two-way “road” connecting manifest and latent aspects, which in one direction involves the work of dream construction and in the other permits the associative process of decoding and interpretation. Freud's more revolutionary hypothesis, whose implications he did not fully elaborate, is that dreams are the expression of a primary mental process that differs qualitatively from waking thought and hence are incomprehensible through a secondary process model. This seems more adequately to account for what is now known about dreaming, and is more consistent with the way dream interpretation is ordinarily conducted in clinical practice. Recognition that dreams are qualitatively distinctive expressions of mind may help to restore dreaming to its privileged position as a unique source of mental status information.
Psychoanalytic Practice in the Early Postgraduate Years
Authors: Cherry Sabrina , Cabaniss Deborah L. , Forand Nicholas , Haywood Dana , Roose Steven P.
Published: November 2012

As a pilot investigation for a longitudinal study of psychoanalytic careers, a survey was conducted of analysts who graduated during the last fifteen years from the Columbia University Center for Psychoanalytic Training and Research. Graduates were asked to describe both their analytic practice and their interest in pursuing appointment as training and supervising analysts. The 23-item questionnaire was completed by 67 of 102 potential respondents (66%). The study identified two subgroups of graduates: those who were not certified and were not training analysts (GAs), 78% of the sample, and certified and training analysts (CAs, TAs), 22% of the sample. GAs started a mean of 1.4 new analytic cases since graduation, as compared to CAs and TAs, who started a mean of 5.4 and 8.3 new cases, respectively. CAs and TAs also saw more twice-weekly therapy cases than did GAs. Once-weekly therapy was the most commonly practiced treatment for all subgroups. Interest in becoming a TA was highest during the first five postgraduate years and was lower among non-TAs five to fifteen years after graduation. Only one of the CA respondents met current APsaA immersion criteria for training analyst appointment.
Boundaries and Postanalytic Contacts in Institutes
Authors: Levine Howard B. , Yanof Judith A.
Published: November 2012

The work of a COPE study group on boundaries is presented, with particular focus on post-termination contact after the training analysis. Through the use of clinical examples evocative and illustrative of the complexity of postanalytic contacts and relationships in the training analysis situation, a number of dilemmas are identified that former analysts and patients face when they meet as colleagues after the training analysis is over. These dilemmas, it is argued, have implications for the conduct and effectiveness of the training analysis and for the institutional cultures and power relations that evolve within institutes.
Success and Succession
Authors: Marill Irwin H. , Siegel Everett R.
Published: November 2012

The etymology of the word success and its relationship to succession is elucidated. Linkage is made to the consequences of unconscious “legitimate” and “illicit” fulfillments in life. This is explored in the writings of Freud and others. Emphasis is placed on guilt, a major factor blocking the attainment of success. This guilt derives from unconscious parricide, which permeates and contaminates themes of succession. How early objects, particularly oedipal ones, are “killed off” in the process of gaining autonomy and achievement without literally invoking unconscious murder is explored. The retaliatory aspects of failure are also addressed. Illustrations employing case material are used to highlight these theoretical constructs.
Music, Mourning, and Consolation
Authors: Stein Alexander
Published: November 2012

The attacks of September 11, 2001, prompt a consideration of the role of music in mourning and trauma. The intrapsychic functions of music in the mourning process are explored, as is music as a unique response to trauma and as a special aesthetic expression of a range of affects connected with grief. Also explored is the allied notion of consolation, a topic underdeveloped in the analytic literature.