bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Characterization of an scFv-Fc Antibody that Immunotherapeutically Targets the Common Cancer Cell Surface Proteoglycan CSPG4
Authors: Wang Xinhui , Katayama Akihiro , Wang Yangyang , Yu Ling , Favoino Elvira , Sakakura Koichi , Favole Alessandra , Tsuchikawa Takahiro , Silver Susan , Watkins Simon C. , Kageshita Toshiro , Ferrone Soldano
Published: October 2011

Cell surface chondroitin sulfate proteoglycan 4 (CSPG4) is an attractive target for antibody-based cancer immunotherapy because of its role in tumor cell biology, its high expression on malignant cells including cancer-initiating cells, and its restricted distribution in normal tissues. The clinical use of CSPG4 has been hampered by the lack of a CSPG4-specific chimeric, humanized, or fully human monoclonal antibody. To overcome this limitation, we generated a CSPG4-specific fully human single-chain antibody termed scFv-FcC21 and characterized its specificity and antitumor activity. Viable CSPG4+ melanoma cells were used in a screen of a human scFv phage display library that included CDR3 engineered to optimize antibody binding sites. The scFv antibody isolated was then recombinantly engineered with a human immunoglobulin G1 Fc region to construct the fully human antibody scFv-FcC21, which recognized tumors of neuroectodermal origin, various types of carcinomas, mesotheliomas, and sarcomas as well as myeloid leukemias. scFv-FcC21 inhibited in vitro growth and migration of tumor cells and in vivo growth of human tumor xenografts. These effects were mediated by inhibition of the activation of extracellular signal–regulated kinase and focal adhesion kinase signaling pathways that are critical for tumor cell growth and migration, respectively. Our findings define the CSPG4-specific fully human scFv-FcC21 antibody as a candidate therapeutic agent to target the many types of tumors that express CSPG4. Cancer Res; 71(24); 7410–22. ©2011 AACR.
Early [18F]Fluorodeoxyglucose Positron Emission Tomography at Two Days of Gefitinib Treatment Predicts Clinical Outcome in Patients with Adenocarcinoma of the Lung
Authors: Takahashi Ryo , Hirata Haruhiko , Tachibana Isao , Shimosegawa Eku , Inoue Atsuo , Nagatomo Izumi , Takeda Yoshito , Kida Hiroshi , Goya Sho , Kijima Takashi , Yoshida Mitsuhiro , Kumagai Toru , Kumanogoh Atsushi , Okumura Meinoshin , Hatazawa Jun , Kawase Ichiro
Published: October 2011

Purpose: Positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) is increasingly used in early assessment of tumor response after chemotherapy. We investigated whether a change in [18F]FDG uptake at 2 days of gefitinib treatment predicts outcome in patients with lung adenocarcinoma.

Experimental Design: Twenty patients were enrolled. [18F]FDG-PET/computed tomographic (CT) scan was carried out before and 2 days after gefitinib treatment. Maximum standardized uptake values (SUV) were measured, and post-gefitinib percentage changes in SUV were calculated. Early metabolic response (SUV decline < −25%) was compared with morphologic response evaluated by CT scan and with progression-free survival (PFS).

Results: At 2 days of gefitinib treatment, 10 patients (50%) showed metabolic response, 8 had metabolic stable disease, and 2 had progressive metabolic disease. Percentage changes of SUV at 2 days were correlated with those of tumor size in CT at 1 month (R2 = 0.496; P = 0.0008). EGFR gene was assessable in 15 patients, and of 12 patients with EGFR mutations, 8 showed metabolic response at 2 days and 6 showed morphologic response at 1 month. None of 3 patients with wild-type EGFR showed metabolic or morphologic response. Metabolic response at 2 days was not statistically associated with PFS (P = 0.095), but when a cutoff value of −20% in SUV decline was used, metabolic responders had longer PFS (P < 0.0001).

Conclusion: Early assessment of [18F]FDG tumor uptake with PET at 2 days of gefitinib treatment could be useful to predict clinical outcome earlier than conventional CT evaluation in patients with lung adenocarcinoma. Clin Cancer Res; 18(1); 220–8. ©2011 AACR.
Micromanaging the Classification of Colon Cancer: The Role of the microRNAome
Authors: Vilar Eduardo , Tabernero Josep , Gruber Stephen B.
Published: October 2011

Recent advances in our understanding of the microRNAome (miRNAome) have provided further insights into the molecular pathogenesis of colorectal cancer and shown a potential role for miRNAs in distinguishing molecular subtypes. The mucosa-adenoma-carcinoma model can now integrate miRNAs into the known genetic alterations that drive the progression of colorectal neoplasia. Clin Cancer Res; 17(23); 7207–9. ©2011 AACR.
Definitions, Criteria and Global Classification of Mast Cell Disorders with Special Reference to Mast Cell Activation Syndromes: A Consensus Proposal
Authors: Valent Peter , Akin Cem , Arock Michel , Brockow Knut , Butterfield Joseph H. , Carter Melody C. , Castells Mariana , Escribano Luis , Hartmann Karin , Lieberman Philip , Nedoszytko Boguslaw , Orfao Alberto , Schwartz Lawrence B. , Sotlar Karl , Sperr Wolfgang R. , Triggiani Massimo , Valenta Rudolf , Horny Hans-Peter , Metcalfe Dean D.
Published: October 2011

Activation of tissue mast cells (MCs) and their abnormal growth and accumulation in various organs are typically found in primary MC disorders also referred to as mastocytosis. However, increasing numbers of patients are now being informed that their clinical findings are due to MC activation (MCA) that is neither associated with mastocytosis nor with a defined allergic or inflammatory reaction. In other patients with MCA, MCs appear to be clonal cells, but criteria for diagnosing mastocytosis are not met. A working conference was organized in 2010 with the aim to define criteria for diagnosing MCA and related disorders, and to propose a global unifying classification of all MC disorders and pathologic MC reactions. This classification includes three types of ‘MCA syndromes’ (MCASs), namely primary MCAS, secondary MCAS and idiopathic MCAS. MCA is now defined by robust and generally applicable criteria, including (1) typical clinical symptoms, (2) a substantial transient increase in serum total tryptase level or an increase in other MC-derived mediators, such as histamine or prostaglandin D2, or their urinary metabolites, and (3) a response of clinical symptoms to agents that attenuate the production or activities of MC mediators. These criteria should assist in the identification and diagnosis of patients with MCAS, and in avoiding misdiagnoses or overinterpretation of clinical symptoms in daily practice. Moreover, the MCAS concept should stimulate research in order to identify and exploit new molecular mechanisms and therapeutic targets.
Adaptive Alternative Splicing Correlates with Less Environmental Risk of Parkinsonism
Authors: BenMoyal-Segal Liat , Soreq Lilach , Ben-Shaul Yoram , Ben-Ari Shani , Ben-Moshe Tehila , Aviel Sigal , Bergman Hagai , Soreq Hermona
Published: October 2011

Background/Objective: Environmental exposure to anti-acetylcholinesterases (AChEs) aggravates the risk of Parkinsonism due to currently unclear mechanism(s). We explored the possibility that the brain’s capacity to induce a widespread adaptive alternative splicing response to such exposure may be involved. Methods: Following exposure to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), brain region transcriptome profiles were tested. Results: Changes in transcript profiles, alternative splicing patterns and splicing-related gene categories were identified. Engineered mice over-expressing the protective AChE-R splice variant showed less total changes but more splicing-related ones than hypersensitive AChE-S over-expressors with similarly increased hydrolytic activities. Following MPTP exposure, the substantia nigra and prefrontal cortex (PFC) of both strains showed a nuclear increase in the splicing factor ASF/SF2 protein. Furthermore, intravenous injection with highly purified recombinant human AChE-R changed transcript profiles in the striatum. Conclusions: Our findings are compatible with the working hypothesis that inherited or acquired alternative splicing deficits may promote parkinsonism, and we propose adaptive alternative splicing as a strategy for attenuating its progression.
Mean Platelet Volume and Integrin Alleles Correlate With Levels of Integrins α
IIb
β
3
and α
2
β
1
in Acute Coronary Syndrome Patients and Normal Subjects
Authors: Kunicki Thomas J. , Williams Shirley A. , Nugent Diane J. , Yeager Mark
Published: October 2011

Objective—

The interindividual variation in platelet α
2
β
1
exceeds a 2-fold variance in platelet α
IIb
β
3
level. Our objective was to parse the contribution of mean platelet volume (MPV) and integrin gene alleles to this variation in large cohorts of patients with acute coronary syndrome (ACS) and normal subjects.

Methods and Results—

Platelet α
IIb
β
3
and α
2
β
1
levels were measured by flow cytometry in whole blood from 320 ACS patients and 128 normal subjects and compared with MPV, platelet count,
ITGA2
rs28095, and
ITGB3
rs5918 alleles. In all subjects, a strong direct correlation was found between MPV and α
IIb
β
3
level (
P
<0.001). Neither MPV nor α
IIb
β
3
level correlated with
ITGB3
rs5918 alleles. In the case of α
2
β
1
level, MPV contributed modestly, whereas
ITGA2
rs28095 exerted a greater effect. An inverse correlation was found between MPV and the rs28095 minor allele.

Conclusion—

MPV is the major effector of platelet α
IIb
β
3
level, whereas the
ITGA2
rs28095 alleles influence α
2
β
1
level more than MPV does. The rs28095 minor allele, associated with lower MPV, likely exerts this effect via the influence of α
2
β
1
on megakaryocyte maturation. Because of the hyperactivity of larger platelets, MPV is an accurate metric of risk for adverse outcome in ACS.
Hemangioma Is Associated with Atopic Disease
Authors: Grimmer J. Fredrik , Williams Marc S. , Pimentel Richard , Mineau Geraldine , Wood Grant M. , Bayrak‐Toydemir Pinar , Stevenson David A.
Published: October 2011

Objective

To determine if atopic disease is associated with infantile hemangioma.

Study Design

Case control study.

Setting

State of Utah inpatient and outpatient records obtained from the Department of Health, Intermountain Healthcare medical records, and the University of Utah Health Care medical records using the Utah Population Database.

Subjects

Patients given an International Classification of Diseases, Ninth Revision diagnosis of hemangioma prior to age 5 years, from 1991 to 2009.

Methods

Allergy, asthma, and eczema rates in the hemangioma cohort compared to randomly matched controls using logistic regression analysis.

Results

The authors identified 2063 patients in the hemangioma group. The overall odds ratio of atopic disease in patients diagnosed with hemangioma was 1.67 compared to the control group (P <. 0001). In the hemangioma cohort, the authors found a 36% increased risk of allergies (P <. 0001), 67% increased risk of asthma (P < 4e‐12), and 82% increased risk of eczema (P < 2e‐16).

Conclusion

This study indicates that allergy, asthma, and eczema are positively associated with hemangioma. Eczema was most strongly associated with hemangioma, with a nearly 2‐fold increased risk. Understanding the relationship between atopic disease and infantile hemangioma may elucidate the pathophysiology of each and ultimately lead to better treatment options.
Relationship Between Proximal Femoral and Acetabular Alignment in Normal Hip Joints Using 3-Dimensional Computed Tomography
Authors: Buller Leonard T. , Rosneck James , Monaco Feno M. , Butler Robert , Smith Travis , Barsoum Wael K.
Published: October 2011

Background: The bony architecture of the hip depends upon functional adaptation to mechanical usage via the dynamic interaction between the acetabulum and femoral head. Acetabular retroversion is thought to be a contributing factor of pincer-type femoroacetabular impingement. Studies of pathological hip joints suggest proximal femoral anatomy compensates for acetabular retroversion.

Hypothesis/Purpose: The purpose of this study was to determine if a predictable relationship exists between proximal femoral and acetabular angles, age, and gender in normal hip joints. We hypothesized that, through functional adaptation to mechanical loading, a complementary developmental relationship exists between the acetabulum and proximal femur.

Study Design: Descriptive laboratory study.

Methods: The femoral neck version, femoral neck shaft angle, acetabular version, acetabular inclination, and center edge angle were measured in 230 normal hip joints in 115 adults using 3-dimensional reconstruction software. Correlations between the angles, age, and gender were examined using the methods of stepwise regression and backward elimination.

Results: Regarding side-to-side comparison and variability, there was no statistically significant difference between the left and right sides in the average value of each angle measurement. The correlations specifically between angles, age, and gender were similar on the left and right sides for all pairs except femoral version and acetabular inclination. Regarding significant findings of the study, a positive correlation ( P < .05) was found between femoral version and acetabular version (0.38° to 1°). A positive correlation was found between femoral neck shaft angle and acetabular version (0.21° to 1°). A negative correlation was found between femoral neck shaft angle and age (–0.17° to 1°). A positive correlation was found between acetabular version and female gender (2.6° to 1°). A positive correlation was found between center edge angle and female gender (2.8° to 1°). A negative correlation was found between femoral version and acetabular inclination (–0.49° to 1°), although this latter relationship was only observed unilaterally (ie, left hip).

Conclusion: This study demonstrates that a correlation exists between multiple proximal femoral and acetabular angles in normal hip joints. These findings support the hypothesis that a complementary developmental relationship occurs between the femoral head and acetabulum.

Clinical Relevance: The results of this study suggest that, in some patients, what is thought to be pathological acetabular retroversion may actually be normal anatomy with a compensated femoral version. Investigating the relationship between these angles in patients with the signs and symptoms of pincer-type femoroacetabular impingement may alter a surgeon’s approach to this patient population.
Electro-mechanical and thermal characteristics of silver-electroded ionic polymer–metal composite actuator
Authors: Biswal D K , Bandopadhya D , Dwivedy S K
Published: October 2011

The proposed work is in line with the evaluation of electro-mechanical and thermal characteristics of silver-electroded ionic polymer–metal composite (IPMC). IPMCs are fabricated first using Nafion-117 as base polymer and non-precious metal silver as surface electrode by chemical decomposition method. Several testings are performed on fabricated IPMC to evaluate its thermo-mechanical and micro-structural properties. The characteristics of the electrode layer and deposited particles on IPMC surface are studied using scanning electron microscope. The bending experiment of the actuator is conducted by applying direct current potential and the tip displacement measured. Thermo-gravimetric analysis and differential scanning calorimetry test are carried out, and thermal stability of the actuator is investigated. The crystal structure of IPMC is investigated by X-ray diffraction analysis. Micro-tensile test of the specimen is carried out to ascertain the stress–strain relationship and comparison is made with the base polymer, Nafion. The experimental investigations, characterization, and performance of the IPMC demonstrate its effectiveness to be used as actuator and artificial muscle materials.
Engineered factor IX variants bypass FVIII and correct hemophilia A phenotype in mice
Authors: Milanov Peter , Ivanciu Lacramioara , Abriss Daniela , Quade-Lyssy Patricia , Miesbach Wolfgang , Alesci Sonja , Tonn Torsten , Grez Manuel , Seifried Erhard , Schüttrumpf Jörg
Published: October 2011

The complex of the serine protease factor IX (FIX) and its cofactor, factor VIII (FVIII), is crucial for propagation of the intrinsic coagulation cascade. Absence of either factor leads to hemophilia, a disabling disorder marked by excessive hemorrhage after minor trauma. FVIII is the more commonly affected protein, either by X-chromosomal gene mutations or in autoimmune-mediated acquired hemophilia. Whereas substitution of FVIII is the mainstay of hemophilia A therapy, treatment of patients with inhibitory Abs remains challenging. In the present study, we report the development of FIX variants that can propagate the intrinsic coagulation cascade in the absence of FVIII. FIX variants were expressed in FVIII-knockout (FVIII-KO) mice using a nonviral gene-transfer system. Expression of the variants shortened clotting times, reduced blood loss after tail-clip assay, and reinstalled clot formation, as tested by in vivo imaging of laser-induced vessel injury. In addition, we confirmed the therapeutic efficacy of FIX variants in mice with inhibitory Abs against FVIII. Further, mice tolerant to wild-type human FIX did not develop immune responses against the protein variants. Our results therefore indicate the feasibility of using variants of FIX to bypass FVIII as a novel treatment approach in hemophilia with and without neutralizing FVIII Abs.
Physical properties of naked DNA influence nucleosome positioning and correlate with transcription start and termination sites in yeast
Authors: Deniz Özgen , Flores Oscar , Battistini Federica , Pérez Alberto , Soler-López Montserrat , Orozco Modesto
Published: October 2011

Background

In eukaryotic organisms, DNA is packaged into chromatin structure, where most of DNA is wrapped into nucleosomes. DNA compaction and nucleosome positioning have clear functional implications, since they modulate the accessibility of genomic regions to regulatory proteins. Despite the intensive research effort focused in this area, the rules defining nucleosome positioning and the location of DNA regulatory regions still remain elusive.

Results

Naked (histone-free) and nucleosomal DNA from yeast were digested by microccocal nuclease (MNase) and sequenced genome-wide. MNase cutting preferences were determined for both naked and nucleosomal DNAs. Integration of their sequencing profiles with DNA conformational descriptors derived from atomistic molecular dynamic simulations enabled us to extract the physical properties of DNA on a genomic scale and to correlate them with chromatin structure and gene regulation. The local structure of DNA around regulatory regions was found to be unusually flexible and to display a unique pattern of nucleosome positioning. Ab initio physical descriptors derived from molecular dynamics were used to develop a computational method that accurately predicts nucleosome enriched and depleted regions.

Conclusions

Our experimental and computational analyses jointly demonstrate a clear correlation between sequence-dependent physical properties of naked DNA and regulatory signals in the chromatin structure. These results demonstrate that nucleosome positioning around TSS (Transcription Start Site) and TTS (Transcription Termination Site) (at least in yeast) is strongly dependent on DNA physical properties, which can define a basal regulatory mechanism of gene expression.
The changing seroepidemiology of enterovirus 71 infection among children and adolescents in Singapore
Authors: Ang Li-Wei , Phoon Meng-Chee , Wu Yan , Cutter Jeffery , James Lyn , Chow Vincent T
Published: October 2011

Background

Enterovirus 71 (EV71) has caused recurrent epidemics of hand, foot and mouth disease among children in Singapore. Between August 2008 and July 2010, we conducted a survey to estimate the seroprevalence of EV71 infection among children and adolescents aged 1-17 years. We compared our EV71 seroepidemiologic findings with a previous study conducted in 1996-1997.

Methods

The survey involved the prospective collection of 1,200 residual sera from Singapore residents aged 1-17 years in two hospitals. Neutralizing antibodies to EV71 were detected by the microneutralization test. The geometric mean titer (GMT) of EV71 antibodies and 95% confidence intervals (CI) were calculated and compared by age groups. Statistical significance was taken asP< 0.05.

Results

The overall EV71 antibody prevalence was 26.9% (95% CI: 24.5-29.5%). It increased significantly from 14.3% in children aged 1-6 years to 27.8% in those aged 7-12 years, and reached 38.8% in adolescents aged 13-17 years. The seroconversion rate differed by about 12% between the consecutive age groups. The GMT of EV71 antibodies was higher among primary school children aged 7-12 years in our study than that among the 6-12 year age group in the 1996-1997 study.

Conclusions

Higher antibody titers were observed in children aged 1-6 years than those in the other two age groups, indicating that most of the infections had been acquired during early childhood. EV71 infection is common among children and adolescents in Singapore, with 39% infected by the time they are in secondary school (13-17 years of age).
The prevalence of hyperuricemia in China: a meta-analysis
Authors: B Liu , T Wang , HN Zhao , WW Yue , HP Yu , CX Liu , J Yin , RY Jia , HW Nie
Published: October 2011

Background

The prevalence of hyperuricemia varied in different populations and it appeared to be increasing in the past decades. Recent studies suggest that hyperuricemia is an independent risk factor for cardiovascular disease. However, there has not yet been a systematic analysis of the prevalence of hyperuricemia in China.

Methods

Epidemiological investigations on hyperuricemia in China published in journals were identified manually and on-line by using CBMDISC, Chongqing VIP database and CNKI database. Those Reported in English journals were identified using MEDLINE database. Selected studies had to describe an original study defined by strict screening and diagnostic criteria. The fixed effects model or random effects model was employed according to statistical test for homogeneity.

Results

Fifty-nine studies were selected, the statistical information of which was collected for systematic analysis. The results showed that the pooled prevalence of hyperuricemia in male was 21.6% (95%CI: 18.9%-24.6%), but it was only 8.6% (95%CI: 8.2%-10.2%) in female. It was found that thirty years was the risk point age in male and it was fifty years in female.

Conclusions

The prevalence of hyperuricemia is different as the period of age and it increases after 30 years in male and 50 in female. Interventions are necessary to change the risk factors before the key age which is 30 years in male and 50 in female.
A fast approach to determine a fed batch feeding profile for recombinant Pichia pastoris strains
Authors: Dietzsch Christian , Spadiut Oliver , Herwig Christoph
Published: October 2011

Background

The microorganism Pichia pastoris is a commonly used microbial host for the expression of recombinant proteins in biotechnology and biopharmaceutical industry. To speed up process development, a fast methodology to determine strain characteristic parameters, which are needed to subsequently set up fed batch feeding profiles, is required.

Results

Here, we show the general applicability of a novel approach to quantify a certain minimal set of bioprocess-relevant parameters, i.e. the adaptation time of the culture to methanol, the specific substrate uptake rate during the adaptation phase and the maximum specific substrate uptake rate, based on fast and easy-to-do batch cultivations with repeated methanol pulses in a batch culture. A detailed analysis of the adaptation of different P. pastoris strains to methanol was conducted and revealed that each strain showed very different characteristics during adaptation, illustrating the need of individual screenings for an optimal parameter definition during this phase. Based on the results obtained in batch cultivations, dynamic feeding profiles based on the specific substrate uptake rate were employed for different P. pastoris strains. In these experiments the maximum specific substrate uptake rate, which had been defined in batch experiments, also represented the upper limit of methanol uptake, underlining the validity of the determined process-relevant parameters and the overall experimental strategy.

Conclusion

In this study, we show that a fast approach to determine a minimal set of strain characteristic parameters based on easy-to-do batch cultivations with methanol pulses is generally applicable for different P. pastoris strains and that dynamic fed batch strategies can be designed on the specific substrate uptake rate without running the risk of methanol accumulation.
Some Coincidence Point Theorems for Nonlinear Contraction in Ordered Metric Spaces
Authors: Shatanawi Wasfi , Mustafa Zead , Tahat Nedal
Published: October 2011

We establish new coincidence point theorems for nonlinear contraction in ordered metric spaces. Also, we introduce an example to support our results. Some applications of our obtained results are given.

MSC: 54H25; 47H10; 54E50; 34B15.
Identification of genotype 4 Hepatitis E virus binding proteins on swine liver cells
Authors: Zhang Wen , Hua Xiuguo , Shen Quan , Yang Shixing , Yin Hong , Cui Li
Published: October 2011

Hepatitis E virus (HEV) is a zoonotic pathogen of which several species of animal were reported as reservoirs. Swine stands out as the major reservoir for HEV infection in humans, as suggested by the close genetic relationship of swine and human virus and cross-species infection of HEV. Up to now, the mechanism of cross-species infection of HEV from swine to humans is still unclear. This study sought to identify receptor element for genotype 4 HEV on swine liver cells using the viral overlay protein binding assay (VOPBA) technique and Mass Spectrometry fingerprinting. A single virus binding band with natural molecular weight about 55 kDa was observed, and mass spectrometry revealed that this virus binding band contained 31 different proteins. Infection inhibition assay suggested that this 55 kDa protein could prevent HEV from infecting its susceptible A549 cell line, which was further confirmed by the HEV genome detecting in the inoculated cells. Further research should be performed to elucidate the accurate receptor of HEV on the swine liver cells.
Adult separation anxiety in patients with complicated grief versus healthy control subjects: relationships with lifetime depressive and hypomanic symptoms
Authors: Dell'Osso Liliana , Carmassi Claudia , Corsi Martina , Pergentini Irene , Socci Chiara , Maremmani Angelo GI , Perugi Giulio
Published: October 2011

Background

Around 9% to 20% of bereaved individuals experience symptoms of complicated grief (CG) that are associated with significant distress and impairment. A major issue is whether CG represents a distinctive nosographic entity, independent from other mental disorders, particularly major depression (MD), and the role of symptoms of adult separation anxiety. The purpose of this study was to compare the clinical features of patients with CG versus a sample of healthy control subjects, with particular focus on adult separation anxiety and lifetime mood spectrum symptoms.

Methods

A total of 53 patients with CG and 50 healthy control subjects were consecutively recruited and assessed by means of the Structured Clinical Interview for DSM-IV Axis-I disorders (SCID-I/P), Inventory of Complicated Grief (ICG), Adult Separation Anxiety Questionnaire (ASA-27), Work and Social Adjustment Scale (WSAS) and Mood Spectrum-Self Report (MOODS-SR) lifetime version.

Results

Patients with CG reported significantly higher scores on the MOODS-SR, ASA-27, and WSAS with respect to healthy control subjects. The scores on the ASA-27 were significantly associated with the MOODS-SR depressive and manic components amongst both patients and healthy control subjects, with a stronger association in the latter.

Conclusions

A major limitation of the present study is the small sample size that may reduce the generalizability of the results. Moreover, lifetime MOODS-SR does not provide information about the temporal sequence of the manic or depressive symptoms and the loss. The frequent comorbidity with MD and the association with both depressive and manic lifetime symptoms do not support the independence of CG from mood disorders. In our patients, CG is associated with high levels of separation anxiety in adulthood. However, the presence of lifetime mood instability, as measured by the frequent presence of depressive and hypomanic lifetime symptoms, suggests that cyclothymia might represent the common underlying feature characterizing the vulnerability to both adult separation anxiety and CG.
The genetic validation of heterogeneity in schizophrenia
Authors: Tsutsumi Atsushi , Glatt Stephen J , Kanazawa Tetsufumi , Kawashige Seiya , Uenishi Hiroyuki , Hokyo Akira , Kaneko Takao , Moritani Makiko , Kikuyama Hiroki , Koh Jun , Matsumura Hitoshi , Yoneda Hiroshi
Published: October 2011

Introduction

Schizophrenia is a heritable disorder, however clear genetic architecture has not been detected. To overcome this state of uncertainty, the SZGene database has been established by including all published case-control genetic association studies appearing in peer-reviewed journals. In the current study, we aimed to determine if genetic variants strongly suggested by SZGene are associated with risk of schizophrenia in our case-control samples of Japanese ancestry. In addition, by employing the additive model for aggregating the effect of seven variants, we aimed to verify the genetic heterogeneity of schizophrenia diagnosed by an operative diagnostic manual, the DSM-IV.

Methods

Each positively suggested genetic polymorphism was ranked according to its p-value, then the seven top-ranked variants (p < 0.0005) were selected from DRD2, DRD4, GRIN2B, TPH1, MTHFR, and DTNBP1 (February, 2007). 407 Schizophrenia cases and 384 controls participated in this study. To aggregate the vulnerability of the disorder based on the participants' genetic information, we calculated the "risk-index" by adding the number of genetic risk factors.

Results

No statistically significant deviation between cases and controls was observed in the genetic risk-index derived from all seven variants on the top-ranked polymorphisms. In fact, the average risk-index score in the schizophrenia group (6.5+/-1.57) was slightly lower than among controls (6.6+/-1.39).

Conclusion

The current work illustrates the difficulty in identifying universal and definitive risk-conferring polymorphisms for schizophrenia. Our employed number of samples was small, so we can not preclude the possibility that some or all of these variants are minor risk factors for schizophrenia in the Japanese population. It is also important to aggregate the updated positive variants in the SZGene database when the replication work is conducted.
Xenorhodopsins, an enigmatic new class of microbial rhodopsins horizontally transferred between archaea and bacteria
Authors: Ugalde Juan A , Podell Sheila , Narasingarao Priya , Allen Eric E
Published: October 2011

Based on unique, coherent properties of phylogenetic analysis, key amino acid substitutions and structural modeling, we have identified a new class of unusual microbial rhodopsins related to the Anabaena sensory rhodopsin (ASR) protein, including multiple homologs not previously recognized. We propose the name xenorhodopsin for this class, reflecting a taxonomically diverse membership spanning five different Bacterial phyla as well as the Euryarchaeotal class Nanohaloarchaea. The patchy phylogenetic distribution of xenorhodopsin homologs is consistent with historical dissemination through horizontal gene transfer. Shared characteristics of xenorhodopsin-containing microbes include the absence of flagellar motility and isolation from high light habitats.

Reviewers: This article was reviewed by Dr. Michael Galperin and Dr. Rob Knight.
A new model for the characterization of infection risk in gunshot injuries:Technology, principal consideration and clinical implementation
Authors: von See Constantin , Rana Majeed , Stoetzer Marcus , Wilker Conrad , Rücker Martin , Gellrich Nils-Claudius
Published: October 2011

Introduction

The extent of wound contamination in gunshot injuries is still a topic of controversial debate. The purpose of the present study is to develop a model that illustrates the contamination of wounds with exogenous particles along the bullet path.

Material and methods

To simulate bacteria, radio-opaque barium titanate (3-6 μm in diameter) was atomized in a dust chamber. Full metal jacket or soft point bullets caliber .222 (n = 12, v0 = 1096 m/s) were fired through the chamber into a gelatin block directly behind it. After that, the gelatin block underwent multi-slice CT in order to analyze the permanent and temporary wound cavity.

Results

The permanent cavity caused by both types of projectiles showed deposits of barium titanate distributed over the entire bullet path. Full metal jacket bullets left only few traces of barium titanate in the temporary cavity. In contrast, the soft point bullets disintegrated completely, and barium titanate covered the entire wound cavity.

Discussion

Deep penetration of potential exogenous bacteria can be simulated easily and reproducibly with barium titanate particles shot into a gelatin block. Additionally, this procedure permits conclusions to be drawn about the distribution of possible contaminants and thus can yield essential findings in terms of necessary therapeutic procedures.
Cardiovascular and renal effects of carperitide and nesiritide in cardiovascular surgery patients: a systematic review and meta-analysis
Authors: Mitaka Chieko , Kudo Toshifumi , Haraguchi Go , Tomita Makoto
Published: October 2011

Introduction

Acute kidney injury (AKI) following cardiovascular surgery is a common disease process and is associated with both morbidity and mortality. The aim of our study was to evaluate the cardiovascular and renal effects of an atrial natriuretic peptide (ANP, carperitide) and a B-type (or brain) natriuretic peptide (BNP, nesiritide) for preventing and treating AKI in cardiovascular surgery patients.

Methods

Electronic databases, including PubMed, EMBASE and references from identified articles were used for a literature search.

Results

Data on the infusion of ANP or BNP in cardiovascular surgery patients was collected from fifteen randomized controlled trials and combined. The infusion of ANP or BNP increased the urine output and creatinine clearance or glomerular filtration rate, and reduced the use of diuretics and the serum creatinine levels. A meta-analysis showed that ANP infusion significantly decreased peak serum creatinine levels, incidence of arrhythmia and renal replacement therapy. The meta-analysis also showed that ANP or BNP infusion significantly decreased the length of ICU stay and hospital stay compared with controls. However, the combined data were insufficient to determine how ANP or BNP infusion during the perioperative period influences long-term outcome in cardiovascular surgery patients.

Conclusions

The infusion of ANP or BNP may preserve postoperative renal function in cardiovascular surgery patients. A large, multicenter, prospective, randomized controlled trial will have to be performed to assess the therapeutic potential of ANP or BNP in preventing and treating AKI in the cardiovascular surgical setting.
Serum thyroglobulin reference values according to NACB criteria in healthy subjects with normal thyroid ultrasound
Authors: Giovanella Luca , Imperiali Mauro , Ferrari Anna , Palumbo Alessia , Furlani Lino , Graziani Maria Stella , Castello Roberto
Published: October 2011

The present study was undertaken to establish serum thyroglobulin (Tg) normal reference values in a large group of healthy subjects.

Four hundred and thirty-eight non-smoking healthy subjects were selected to assess the Tg reference values (209 males, 229 non-pregnant females, age 34.7±13.1 years). Inclusion criteria were: no personal or familial history of thyroid disease, thyrotropin levels from 0.5 to 2.00 mUI/L, negative thyroperoxidase and thyroglobulin antibodies. In addition, the patients had a normal size thyroid (females ≤18 mL, males ≤25 mL) without nodules on the thyroid ultrasound (TUS). According to National Academy of Clinical Biochemistry (NACB) criteria the Tg results were transformed to a logarithmic scale and reference ranges were calculated as mean±2 SD.

Serum Tg was measured on the Beckman Coulter UniCel DxI 800 automated platform by the simultaneous 1-step immunoenzymatic Access Thyroglobulin assay (Beckmann-Coulter SA, Nyon, Switzerland). Serum Tg levels were higher in females than in males (p=0.0022). Accordingly, gender-specific reference values were calculated (i.e., males: 1.40–29.2 ng/mL; females: 1.50–38.5 ng/mL).

To the best of the authors’ knowledge, the first reference interval study for Tg that integrates NACB criteria and TUS assessment for the selection of the reference population is provided here.
Integrating Global Regulatory Input Into theSalmonellaPathogenicity Island 1 Type III Secretion System
Authors: Golubeva Yekaterina A , Sadik Adam Y , Ellermeier Jeremy R , Slauch James M
Published: October 2011

Salmonella enterica serovar Typhimurium uses the Salmonella pathogenicity island 1 (SPI1) type III secretion system to induce inflammatory diarrhea and bacterial uptake into intestinal epithelial cells. The expression of hilA, encoding the transcriptional activator of the SPI1 structural genes, is directly controlled by three AraC-like regulators, HilD, HilC, and RtsA, each of which can activate the hilD, hilC, rtsA, and hilA genes, forming a complex feed-forward regulatory loop. A large number of factors and environmental signals have been implicated in SPI1 regulation. We have developed a series of genetic tests that allows us to determine where these factors feed into the SPI1 regulatory circuit. Using this approach, we have grouped 21 of the known SPI1 regulators and environmental signals into distinct classes on the basis of observed regulatory patterns, anchored by those few systems where the mechanism of regulation is best understood. Many of these factors are shown to work post-transcriptionally at the level of HilD, while others act at the hilA promoter or affect all SPI1 promoters. Analysis of the published transcriptomic data reveals apparent coregulation of the SPI1 and flagellar genes in various conditions. However, we show that in most cases, the factors that affect both systems control SPI1 independently of the flagellar protein FliZ, despite its role as an important SPI1 regulator and coordinator of the two systems. These results provide a comprehensive model for SPI1 regulation that serves as a framework for future molecular analyses of this complex regulatory network.
Os desafios éticos nas organizações modernas
Authors: Enriquez Eugène
Published: October 2011

O reaparecimento das preocupações éticas traduz o profundo mal-estar de nossas sociedades em conseqüência do triunfo da racionalidade instrumental, que tende a fazer dos seres humanos objetos manipuláveis. Esta perversão da racionalidade manifesta-se particularmente nas empresas que atualmente procuram integrar a preocupação ética dentro de seu funcionamento. Pode-se constatar que, agindo desta forma, elas têm como objetivo, na maior parte das vezes, desenvolver um forte consenso em torno de seus próprios ideais tanto da parte de seus membros quanto do conjunto do corpo social. Devemos nos perguntar quais são os verdadeiros desafios é ticos com os quais as organizações modernas se confrontam. Com este objetivo, são revistos os conceitos de ética da convicção, da responsabilidade e da discussão. Uma quarta forma de ética, a ética da finitude, é vislumbrada. As organizações podem lhe dar um lugar? A questão merece, em todo caso, ser formulada.
Funcionalidades ambientais de solos altomontanos na Serra da Igreja, Paraná
Authors: Scheer Maurício Bergamini , Curcio Gustavo Ribas , Roderjan Carlos Vellozo
Published: October 2011

Apesar de ainda existirem ecossistemas altomontanos no Paraná em excelente estado de conservação, iminentes ameaças antrópicas e a fragilidade desses ambientes têm sido motivos de preocupação. Este trabalho teve os seguintes objetivos: caracterizar solos de área representativa dos campos e florestas altomontanas ocorrentes na Serra da Igreja; apontar quais os possíveis fatores pedológicos que resultam nessas diferentes fitotipias; e caracterizar algumas das suas funcionalidades ambientais (estoque de C e de água). Os principais solos encontrados nos campos foram Organossolos Fólicos fíbricos/sápricos (líticos e típicos) e Organossolos Háplicos fíbricos/sápricos (típicos e térricos) e, nas florestas altomontanas, Gleissolos Háplicos alíticos típicos. Ambas as classes são de solos distróficos, extremamente ácidos, com alta saturação por Al trocável e altos teores de C orgânico total. A distribuição das florestas altomontanas está fortemente controlada por vales e colos de cumeeiras, os quais estão sujeitos a processos morfogenéticos que resultam em solos com horizontes minerais. Já os campos estão estabelecidos em topos, onde processos pedogenéticos promoveram espessamento de horizontes hísticos, os quais, em função de suas características intrínsecas, aliadas aos fortes ventos, parecem conter com sucesso o avanço da floresta sobre o campo. Os estoques de C por unidade de área nos solos dos campos são superiores aos dos solos das florestas altomontanas, sendo ambos considerados altos quando comparados aos dados de outros ecossistemas, sendo duas a três vezes maiores do que os encontrados em solos de ecossistemas de altitudes mais baixas na mesma latitude. Também foi constatada alta capacidade de retenção hídrica devido à porosidade total verificada nos horizontes hísticos, os quais têm o potencial de reter em média 12 vezes seu volume em água.
Water retention in a peatland with organic matter in different decomposition stages
Authors: Rocha Campos José Ricardo da , Silva Alexandre Christófaro , Fernandes José Sebastião Cunha , Ferreira Mozart Martins , Silva Daniel Valladão
Published: October 2011

Peatlands are ecosystems formed by successive pedogenetic processes, resulting in progressive accumulation of plant remains in the soil column under conditions that inhibit the activity of most microbial decomposers. In Diamantina, state of Minas Gerais, Brazil, a peatland is located at 1366 m asl, in a region with a quartz-rich lithology and characteristic wet grassland vegetation. For this study, the peat area was divided in 12 transects, from which a total of 90 soil samples were collected at a distance of 20 m from each other. The properties rubbed fiber content (RF), bulk density (Bd), mineral material (MM), organic matter (OM), moisture (Moi) and maximum water holding capacity (MWHC) were analyzed in all samples. From three selected profiles of this whole area, samples were collected every 27 cm from the soil surface down to a depth of 216 cm. In these samples, moisture was additionally determined at a pressure of 10 kPa (Moi10) or 1500 kPa (Moi1500), using Richards' extractor and soil organic matter was fractionated by standard procedures. The OM decomposition stage of this peat was found to increase with soil depth. Moi and MWHC were highest in layers with less advanced stages of OM decomposition. The humin levels were highest in layers in earlier stages of OM decomposition and with higher levels of water retention at MWHC and Moi10. Humic acid contents were higher in layers at an intermediate stage of decomposition of organic matter and with lowest levels of water retention at MWHC, Moi10 and Moi1500.
O uso de amostras peneiradas a dois milímetros subestima a proteção física da matéria orgânica no solo
Authors: Tomazi Michely , Bayer Cimélio , Conceição Paulo César
Published: October 2011

O fracionamento físico densimétrico é uma importante ferramenta no estudo da proteção física da matéria orgânica (MO) em agregados de solo, porém seus resultados podem ser alterados pela malha da peneira utilizada no preparo da amostra. A hipótese do presente estudo é de que a desagregação excessiva do solo pelo uso de peneira de 2 mm libera MO originalmente protegida dentro de agregados e, portanto, subestima o teor de C na fração leve-oclusa (C-FLO) e a magnitude da proteção física da MO intra-agregados, em comparação à peneira de 9,5 mm. Amostras (0-5 cm) de cinco solos foram coletadas em experimentos de longa duração (9-18 anos) nas regiões Centro-Oeste (quatro solos) e Sul do Brasil (um solo), sob sistemas de manejo convencional e conservacionista. Tomando as amostras < 9,5 mm como referência, verificou-se subestimação de 2,9 a 15,7 % no C-FLO quando utilizadas amostras < 2,0 mm, a qual foi mais expressiva nos sistemas conservacionistas de manejo de solo e positivamente correlacionada com os teores de C no solo (r = 0,92, p < 0,04), massa de macroagregados > 2 mm (r = 0,90, p < 0,02) e índice de estabilidade de agregados (r = 0,94, p < 0,01). Em três dos cinco solos estudados, o uso de amostras < 2,0 mm levou à conclusão errônea de que os sistemas conservacionistas de manejo do solo não são efetivos na proteção física da MO do solo. Em estudos da proteção física da MO intra-agregados indica-se o uso da peneira de malha de 9,5 mm no preparo da amostra ou, alternativamente, da mesma malha da peneira empregada na preparação de amostras para avaliação da estabilidade de agregados, usualmente 8 mm ou maior.
Produtividade, qualidade dos frutos e distribuição do sistema radicular da melancia em diferentes sistemas de cultivo
Authors: Rocha Marta Rodrigues da , Eltz Flávio Luiz Foletto , Santos Michele Silva dos , Rocha Pedro Vanti da , Goulart Rafael Ziani
Published: October 2011

A melancia é cultivada principalmente por pequenos produtores, em solos arenosos sob preparo convencional, com ocorrência de altas taxas de erosão, já que a cultura não forma dossel vegetativo capaz de cobrir inteiramente o solo. Com o objetivo de avaliar a cultura da melancia (Citrullus lanatus L.) em diferentes sistemas de cultivo, sobre um Argissolo Vermelho distrófico arênico na Depressão Central do RS, foi desenvolvido um experimento durante o ano agrícola 2008/2009 com a cultivar Crimson Sweet. Em parcelas de 48 m² e delineamento em blocos ao acaso com quatro repetições, foram testados os seguintes sistemas de cultivo: preparo convencional (PC), plantio direto (PD), PD escarificado com uma haste de escarificador (PD1H), PD escarificado com duas hastes de escarificador (PD2H), PD escarificado com três hastes de escarificador (PD3H), PD escarificado com quatro hastes de escarificador (PD4H) e PD escarificado com cinco hastes de escarificador (PD5H), com espaçamento entre hastes de 0,35 m. Os dados foram comparados pelo teste de Duncan (p < 5 %). A melancia foi semeada em novembro de 2008, com espaçamento de 2,20 x 0,75 m, sobre palhada de aveia-preta (Avena strigosa). Além da produtividade de melancia, considerando os frutos comercializáveis (> 6 kg), foram determinadas a área superficial e a distribuição do sistema radicular no perfil do solo perpendicular à linha de semeadura (30 e 60 d após a semeadura). Também foram determinadas a densidade do solo e a resistência à penetração após o ciclo. No tratamento PC obteve-se a maior produtividade (126 t ha-1), diferenciando-se estatisticamente dos demais. A área total de raízes aumentou com a intensidade de mobilização e área mobilizada de solo, exceto para o tratamento PD4H. No tratamento PC, a densidade do solo não mostrou diferença em profundidade, porém nos demais tratamentos houve diferença entre a camada de 0-5 cm e as mais profundas. A resistência à penetração na camada de 0-10 cm foi menor, o que pode ter favorecido a maior concentração de raízes nessa camada.