bluuebunny/crossref_metadata_2025 huggingface dataset:
Learning about gravity: segmental assessment of upright control as infants develop independent sitting
Authors: Saavedra Sandra L. , van Donkelaar Paul , Woollacott Marjorie H.
Published: July 2012

The question of how infants attain upright sitting is at the core of understanding the development of most functional abilities. Our simple, practical method of securing the hips and different trunk segments while evaluating the infant's ability to vertically align and stabilize the trunk in space contributes a useful method and new insights into the development of upright control. Previous studies have considered the trunk to develop as a single segment. The goal of the present study was to examine how postural control changes across multiple trunk segments during typical development (TD) of sitting balance. For this purpose, electromyography (EMG) and kinematic data were collected at four levels of trunk support (axillae, midribs, waist, hips), in a longitudinal study of eight TD infants (3–9 mo of age). We found that developmental changes in stability were specific to the region of the trunk being investigated, changes in antagonistic muscle activity differed for the anterior-posterior versus the medial-lateral axis, and the relationship between muscle activation and movement changed from erratic attempts to gain upright position to anticipatory graded responses as infants developed upright control through a four-stage behavioral process. This information can be used by researchers to further refine hypotheses regarding this developmental process and by clinicians who wish to develop and test more specific treatment programs for children with postural dysfunction.
Systematic Framework for Reflectarray Synthesis Based on Phase Optimization
Authors: Álvarez J. , Arrebola M. , Ayestarán R. G. , Las-Heras F.
Published: July 2012

A new systematic synthesis framework for reflectarray antennas is discussed. Optimization based on the Levenberg-Marquardt algorithm is used to obtain the phase distribution of the reflection coefficients required on the reflectarray surface, in order to achieve the pattern specifications. A Local Multipoint Distribution System (LMDS) base station working in the 24.5–26.5 GHz frequency band has been proposed to evaluate the method. The 3D requirements are defined by the combination of the elevation and templates and considering a maximum acceptable ripple in the beam shaping. Some illustrative results are obtained.
Diagnosing Growth Hormone Deficiency in Adults
Authors: Glynn Nigel , Agha Amar
Published: July 2012

Adult growth hormone (GH) deficiency is a recognised syndrome associated with adverse phenotypic, metabolic, and quality-of-life features which improve in many patients when GH is substituted. The appropriate selection of patients at risk of growth hormone deficiency (GHD) is the crucial first step in arriving at a correct diagnosis. Although multiple diagnostic modalities are available including a 24-hour serum GH profile, stimulated GH levels, and insulin-like growth factor-1 (IGF-1) levels, the use of dynamic tests for GH reserves is required in most cases. This paper discusses the utility and drawbacks of the various testing modalities with reference to international guidelines. Regardless of the test chosen, clinical pitfalls including age and obesity must be taken into account. In addition, there is considerable analytical variation in the biochemical measurements of GH and IGF-1 which must be considered before making a diagnosis of GHD in adulthood.
Validation of a Radiosensitivity Molecular Signature in Breast Cancer
Authors: Eschrich Steven A. , Fulp William J. , Pawitan Yudi , Foekens John A. , Smid Marcel , Martens John W.M. , Echevarria Michelle , Kamath Vidya , Lee Ji-Hyun , Harris Eleanor E. , Bergh Jonas , Torres-Roca Javier F.
Published: July 2012

Purpose: Previously, we developed a radiosensitivity molecular signature [radiosensitivity index (RSI)] that was clinically validated in 3 independent datasets (rectal, esophageal, and head and neck) in 118 patients. Here, we test RSI in radiotherapy (RT)-treated breast cancer patients.

Experimental Design: RSI was tested in 2 previously published breast cancer datasets. Patients were treated at the Karolinska University Hospital (n = 159) and Erasmus Medical Center (n = 344). RSI was applied as previously described.

Results: We tested RSI in RT-treated patients (Karolinska). Patients predicted to be radiosensitive (RS) had an improved 5-year relapse-free survival when compared with radioresistant (RR) patients (95% vs. 75%, P = 0.0212), but there was no difference between RS/RR patients treated without RT (71% vs. 77%, P = 0.6744), consistent with RSI being RT-specific (interaction term RSI × RT, P = 0.05). Similarly, in the Erasmus dataset, RT-treated RS patients had an improved 5-year distant metastasis-free survival over RR patients (77% vs. 64%, P = 0.0409), but no difference was observed in patients treated without RT (RS vs. RR, 80% vs. 81%, P = 0.9425). Multivariable analysis showed RSI is the strongest variable in RT-treated patients (Karolinska, HR = 5.53, P = 0.0987, Erasmus, HR = 1.64, P = 0.0758) and in backward selection (removal α of 0.10), RSI was the only variable remaining in the final model. Finally, RSI is an independent predictor of outcome in RT-treated ER+ patients (Erasmus, multivariable analysis, HR = 2.64, P = 0.0085).

Conclusions: RSI is validated in 2 independent breast cancer datasets totaling 503 patients. Including prior data, RSI is validated in 5 independent cohorts (621 patients) and represents, to our knowledge, the most extensively validated molecular signature in radiation oncology. Clin Cancer Res; 18(18); 5134–43. ©2012 AACR.
Vitamin E Protects against Lipid Peroxidation and Rescues Tumorigenic Phenotypes in Cowden/Cowden-like Patient-Derived Lymphoblast Cells with Germline SDHx Variants
Authors: Ni Ying , Eng Charis
Published: July 2012

Purpose: Cowden syndrome (CS), a Mendelian autosomal-dominant disorder, predisposes to breast, thyroid, and other cancers. Germline variations in succinate dehydrogenase genes (SDHx) occur in approximately 10% PTEN mutation-negative CS and CS-like (CSL) individuals (SDHvar+). We previously showed that SDHx variants result in elevated reactive oxygen species (ROS), disruption of nicotinamide adenine dinucleotide (NAD) equilibrium, and destabilization of p53 hence apoptosis resistance in CS/CSL patient-derived lymphoblastoid cells. In the present study, we sought to address the tumorigenic impacts of increased ROS and the potential of protecting SDHvar+ cells with antioxidants.

Experimental Design: We measured the lipid peroxidation levels in patient-derived SDHvar+ lymphoblastoid cells and sequenced 74 controls or SDHvar+ germline DNA samples for mitochondrial hypervariable region II (HVRII) polymorphisms. SDHvar+ lymphoblastoid cells were treated with various antioxidants to check p53 expression and sub-G1 cell population with cell-cycle analysis.

Results: We showed that elevated ROS results in higher lipid peroxidation in SDHvar+ cells. Accumulation of polymorphisms in mitochondrial HVRII was observed in SDHvar+ samples. Interestingly, α-tocopherol (vitamin E) treatment, but not other antioxidants, rescued SDHvar+ cells from apoptosis resistance and protected SDHvar+ cells from oxidative damage such as decreased lipid peroxidation as well as partially recovered p53 expression and NAD/NADH levels.

Conclusions: We conclude that disruption of complex II because of SDHx variants leads to increased ROS generation, specifically accompanied by lipid peroxidation. The lipid soluble antioxidant α-tocopherol can selectively protect SDHvar+ cells from oxidative damage, apoptosis resistance, and rebalance redox metabolites NAD/NADH. Clin Cancer Res; 18(18); 4954–61. ©2012 AACR.
Novel Assessment of Temporal Variation in Fractionated Electrograms Using Histogram Analysis of Local Fractionation Interval in Patients With Persistent Atrial Fibrillation
Authors: Lin Yenn-Jiang , Suenari Kazuyoshi , Lo Men-Tzung , Lin Chen , Hsieh Wan-Hsin , Chang Shih-Lin , Lo Li-Wei , Hu Yu-Feng , Cheng Chen-Chuan , Kihara Yasuki , Chao Tze-Fan , Hartono Beny , Wu Tsu-Juey , Lin Wei-Shiang , Hsu Ke-Hsin , Kibos Ambrose S. , Huang Norden E. , Chen Shih-Ann
Published: July 2012

Background—

The characteristics of atrial electrograms associated with atrial fibrillation (AF) termination are controversial. We investigated the electrogram characteristics that indicate procedural AF termination during continuous complex fractionated electrogram ablation.

Methods and Results—

Fifty-two consecutive patients with persistent AF (47 men; aged 54±9 years), who underwent electrogram-based catheter ablation in the left atrium and coronary sinus after pulmonary vein isolation, were enrolled. The intracardiac bipolar atrial electrogram recordings were characterized by (1) fractionation interval (FI) analysis (>6 seconds), (2) kurtosis (shape of the FI histogram), and (3) skewness (asymmetry of the FI histogram). Sites showing complex, fractionated electrograms (mean FI ≤60 ms) were targeted, and AF was terminated in 20 patients (38%) after the pulmonary vein isolation. The conventional complex fractionated electrogram sites (mean ≤120 ms) in patients with AF termination exhibited higher median kurtosis (2.69 [interquartile range, 2.03–3.46] versus 2.35 [interquartile range, 1.79–2.48];
P
=0.024) and higher complex fractionated electrogram-mean interval (102.7±19.8 versus 87.7±15.0;
P
=0.008) than patients without AF termination. Furthermore, AF termination sites had higher median kurtosis than targeted sites without AF termination (5.13 [interquartile range, 3.51–6.47] versus 4.18 [interquartile range, 2.91–5.34];
P
<0.01) in patients with procedural termination. In addition, patients with AF termination had a higher sinus rhythm maintenance rate after a single procedure than patients without AF termination (log-rank test,
P
=0.007).

Conclusions—

A kurtosis analysis using the FI histogram may be a useful tool in identifying the critical substrate for persistent AF and potential responders to catheter ablation.
Impaired Natural Killer Cell Phenotype and Function in Idiopathic and Heritable Pulmonary Arterial Hypertension
Authors: Ormiston Mark L. , Chang Chiwen , Long Lu L. , Soon Elaine , Jones Des , Machado Rajiv , Treacy Carmen , Toshner Mark R. , Campbell Kate , Riding Alex , Southwood Mark , Pepke-Zaba Joanna , Exley Andrew , Trembath Richard C. , Colucci Francesco , Wills Mark , Trowsdale John , Morrell Nicholas W.
Published: July 2012

Background—

Beyond their role as innate immune effectors, natural killer (NK) cells are emerging as important regulators of angiogenesis and vascular remodeling. Pulmonary arterial hypertension (PAH) is characterized by severe pulmonary vascular remodeling and has long been associated with immune dysfunction. Despite this association, a role for NK cells in disease pathology has not yet been described.

Methods and Results—

Analysis of whole blood lymphocytes and isolated NK cells from PAH patients revealed an expansion of the functionally defective CD56
−
/CD16
+
NK subset that was not observed in patients with chronic thromboembolic pulmonary hypertension. NK cells from PAH patients also displayed decreased levels of the activating receptor NKp46 and the killer immunoglobulin-like receptors 2DL1/S1 and 3DL1, reduced secretion of the cytokine macrophage inflammatory protein-1β, and a significant impairment in cytolytic function associated with decreased killer immunoglobulin-like receptor 3DL1 expression. Genotyping patients (n=222) and controls (n=191) for killer immunoglobulin-like receptor gene polymorphisms did not explain these observations. Rather, we show that NK cells from PAH patients exhibit increased responsiveness to transforming growth factor-β, which specifically downregulates disease-associated killer immunoglobulin-like receptors. NK cell number and cytotoxicity were similarly decreased in the monocrotaline rat and chronic hypoxia mouse models of PAH, accompanied by reduced production of interferon-γ in NK cells from hypoxic mice. NK cells from PAH patients also produced elevated quantities of matrix metalloproteinase 9, consistent with a capacity to influence vascular remodeling.

Conclusions—

Our work is the first to identify an impairment of NK cells in PAH and suggests a novel and substantive role for innate immunity in the pathobiology of this disease.
You Can’t Win If You Don’t Fight
Authors: Getmansky Anna
Published: July 2012

What effect, if any, does democracy have on outcomes of counterinsurgency wars? Previous studies have provided inconclusive answers mainly because of the challenges involved in testing the question empirically: First, insurgencies are not accidental and the anticipated outcomes also affect whether they break out in the first place. Second, regimes are non-random and their determinants can also affect insurgency incidence and its outcomes. Moreover, different aspects of democracy can have opposite effects on the government's chances of winning. I address these challenges by conducting a critical test to distinguish between different causal mechanisms. I find that domestic institutions that are associated with public goods provision make insurgency onsets less likely. I also show that once we control for this selection effect, domestic political institutions do not influence insurgency outcomes.
Time to Kill
Authors: Brancati Dawn , Snyder Jack L.
Published: July 2012

Elections constitute a fundamental element of postconflict peacebuilding efforts in the post–cold war era and are often held soon after conflicts end. Yet, the impact of early elections on postconflict stability is the subject of sharp debate. While some argue that early elections facilitate peace agreements, hasten democratization, and ensure postconflict stability, others suggest that they undermine genuine democracy and spark a renewal in fighting. In this study, we argue that holding elections soon after a civil war ends generally increases the likelihood of renewed fighting, but that favorable conditions, including decisive victories, demobilization, peacekeeping, power sharing, and strong political, administrative and judicial institutions, can mitigate this risk. We attempt to reconcile the extant qualitative debate on postconflict elections through a quantitative analysis of all civil wars ending in the post–World War II period.
Trends, Correlates, and Disease Patterns of Antidepressant Use Among Children and Adolescents in Taiwan
Authors: Chien I-Chia , Hsu Yuan-Chang , Tan Happy Kuy-Lok , Lin Ching-Heng , Cheng Shu-Wen , Chou Yiing-Jenq , Chou Pesus
Published: July 2012

The authors used a population-based database to investigate antidepressant use among children and adolescents in Taiwan. The National Health Research Institutes provided a database of 1 000 000 random subjects for study. The authors adopted this sample of subjects who were younger than 18 years during 1997 to 2005. Subjects with at least 1 antidepressant prescription were identified. Trends, prevalence, associated factors, and disease patterns of antidepressant use were detected. The 1-year prevalence of pediatric antidepressant use increased from 0.27% in 1997 to 0.47% in 2005. The 1-year prevalence of tricyclic antidepressant, selective serotonin reuptake inhibitor, and other antidepressant use among pediatric population was 0.23%, 0.20%, and 0.08%, respectively, in 2005. The prevalence of pediatric antidepressant use increased from 1997 to 2005. Among pediatric subjects with antidepressant use, selective serotonin reuptake inhibitors, and other antidepressants were used the most for psychiatric disorders, whereas tricyclic antidepressant was used the most for nonpsychiatric disorders.
Moebius Syndrome and Hydrosyringomyelia
Authors: Losito Luciana , Gennaro Leonarda , Cacudi Marilena , Rinaldis Marta De , Trabacca Antonio
Published: July 2012

The diagnosis of Moebius syndrome, a rare congenital disorder, is primarily based on congenital facial and abducent nerve palsy. Involvement of other cranial nerves is also common. Occasionally the V, X, XI, and XII cranial nerves are involved, resulting in a difficulty to chew, swallow, and cough, which often leads to respiratory complications. Mental retardation and autism have been reported in some cases. Moebius syndrome can be associated with orofacial anomalies and limb malformations. The authors describe a patient with a confirmed diagnosis of Moebius syndrome associated with hydrosyringomyelia. No case of Moebius syndrome involving primarily the spinal cord has been reported so far. This patient did not present with other factors directly linked to syringomyelia.
Primary Ewing’s Sarcoma/Primitive Neuroectodermal Tumor (ES/PNET) of the Penis
Authors: Ma Zheng , Brimo Fadi , Zeizafoun Nebras
Published: July 2012

Ewing’s sarcomas/primitive neuroectodermal tumors (ES/PNETs) arise from a multipotent progenitor cell and are considered to be of neuroectodermal derivation. Most tumors commonly arise in the skeletal system, which are the classic ES/PNET and occasionally occur in the soft tissue of extraskeletal sites, which are named extraskeletal Ewing’s sarcomas (EES/PNET). This study reports a case of a 28-year-old man with primary EES/PNET of the penis.
The Jones Fracture Classification, Management, Outcome, and Complications
Authors: Dean Benjamin John Floyd , Kothari Alpesh , Uppal Harpal , Kankate Raghubir
Published: July 2012

Background. The Jones fracture has been a topic of controversy ever since being first described by Sir Robert Jones himself in 1902. The aim of this review is to summarize the classification, management, outcome, and complications of this particular injury. Methods. The authors conducted a systematic review of the scientific literature regarding the Jones fracture. Results. There was no consistent approach to the Jones fracture classification. The rate of nonunion with nonoperative treatment is high in both acute and chronic cases. Surgical intervention reduces the incidence of nonunion, but the complication rate of surgery is high. Conclusions. Surgical intervention for the acute Jones fracture should be reserved for the athletic individual because there is a clear advantage in terms of time to return to sporting activity. Nonoperative treatment remains a viable alternative to surgery in all acute and delayed cases, providing there is no established nonunion and the patient is aware of the implications.

Level of Evidence: Therapeutic, Level IV
PLADO and kids: earlier/increased bleeding after HSCT
Authors: Silliman Christopher C.
Published: July 2012

In this issue of Blood, Josephson et al report age group analyses of patients enrolled in the prophylactic platelet dose trial (PLADO) that evaluated the relationship between platelet dose per transfusion and bleeding in hospitalized patients with treatment-induced hypoproliferative thrombocytopenia.1
Comparative molecular analysis of chemolithoautotrophic bacterial diversity and community structure from coastal saline soils, Gujarat, India
Authors: Yousuf Basit , Sanadhya Payal , Keshri Jitendra , Jha Bhavanath
Published: July 2012

Background

Soils harbour high diversity of obligate as well as facultative chemolithoautotrophic bacteria that contribute significantly to CO2dynamics in soil. In this study, we used culture dependent and independent methods to assess the community structure and diversity of chemolithoautotrophs in agricultural and coastal barren saline soils (low and high salinity). We studied the composition and distribution of chemolithoautotrophs by means of functional marker genecbbLencoding large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase and a phylogenetic marker 16S rRNA gene. ThecbbLform IA and IC genes associated with carbon fixation were analyzed to gain insight into metabolic potential of chemolithoautotrophs in three soil types of coastal ecosystems which had a very different salt load and sulphur content.

Results

IncbbLlibraries, thecbbLform IA was retrieved only from high saline soil whereas form IC was found in all three soil types. The form ICcbbLwas also amplified from bacterial isolates obtained from all soil types. A number of novel monophyletic lineages affiliated with form IA and IC phylogenetic trees were found. These were distantly related to the knowncbbLsequences from agroecosystem, volcanic ashes and marine environments. In 16S rRNA clone libraries, the agricultural soil was dominated by chemolithoautotrophs (Betaproteobacteria) whereas photoautotrophicChloroflexiand sulphide oxidizers dominated saline ecosystems. Environmental specificity was apparently visible at both higher taxonomic levels (phylum) and lower taxonomic levels (genus and species). The differentiation in community structure and diversity in three soil ecosystems was supported by LIBSHUFF (P = 0.001) and UniFrac.

Conclusion

This study may provide fundamentally new insights into the role of chemolithoautotrophic and photoautotrophic bacterial diversity in biochemical carbon cycling in barren saline soils. The bacterial communities varied greatly among the three sites, probably because of differences in salinity, carbon and sulphur contents. ThecbbLform IA-containing sulphide-oxidizing chemolithotrophs were found only in high saline soil clone library, thus giving the indication of sulphide availability in this soil ecosystem. This is the first comparative study of the community structure and diversity of chemolithoautotrophic bacteria in coastal agricultural and saline barren soils using functional (cbbL) and phylogenetic (16S rDNA) marker genes.
Association of cardiac and renal function with extreme N-terminal fragment Pro-B-type natriuretic peptide levels in elderly patients
Authors: Cui Hua , Huo Guoliang , Liu Lin , Fan Li , Ye Ping , Cao Jian , Bai Yongyi , Wang Fan , Hu Yixin
Published: July 2012

Background

The data are inconsistent regarding whether extreme N-terminal fragment pro-B-type natriuretic peptide (NT pro-BNP) levels are associated with impaired renal function. Furthermore, the relationship between extreme NT pro-BNP levels and cardiac and renal function in elderly patients has not been reported. The aim of the present study was to examine a hypothesis that extreme NT pro-BNP levels may be associated with impaired cardiac and renal function in elderly patients.

Methods

We retrospectively analyzed the data of demographic, clinical, and echocardiographic features on 152 consecutive elderly patients aged more than 80 years old (average age, 83.65 ± 3.58 years) with NT pro-BNP levels ≥ 3000 pg/ml. The participants were divided into two categories according to their NT pro-BNP levels: (1) 3000–10000 pg/mL and (2) >10000 pg /mL.

Results

The number of patients with impaired renal function (P = 0.019) and the mortality (P < 0.001) in the period of inpatient was higher in the group with NT pro-BNP > 10000 pg /mL. The levels of serum creatinine and creatine kinase MB (CK-MB) in the group of NT pro-BNP > 10000 pg / mL were higher than those in the group of NT pro-BNP = 3000-10000 pg/mL (P = 0.001 and P = 0.023, respectively). Furthermore, no significant difference in the distribution by NYHA class in different NT pro-BNP levels was observed. Multiple linear regression analyses demonstrated that with NT pro-BNP levels as the dependent variable, NT pro-BNP levels were positively correlated with CK-MB (β = 0.182, P = 0.024) and creatinine levels (β = 0.281, P = 0.001). The area under the receiver-operating characteristic (ROC) curve of NT pro-BNP levels and clinical diagnosis of impaired renal function was 0.596 and reached significant difference (95%CI:0.503-0.688, P = 0.044).

Conclusion

These data suggest that the extreme elevation of NT pro-BNP levels (≥3000 pg/ml) is mainly determined by impaired renal function in elderly patients above 80 years. Extreme NT pro-BNP levels may be useful for assessing the severity of impaired renal function.
Long-term treatment with alendronate increases the surgical difficulty during simple exodontias – an in vivo observation in Holtzman rats
Authors: Conte-Neto Nicolau , Bastos Alliny de Souza , Spolidorio Luis Carlos , Chierici Marcantonio Rosemary Adriana , Marcantonio Jr Elcio
Published: July 2012

Background

Atraumatic teeth extractions protocols are highly encouraged in patients taking bisphosphonates (Bps) to reduce surgical trauma and, consequently, the risk of jaws osteonecrosis development. In this way, this paper aims to report the findings of increased surgical difficulty during simple exodontias in animals treated with bisphosphonates.

Methods

Sixty male Holtzman rats were randomly distributed into three groups of 20 animals and received daily subcutaneous administration of 1 mg/kg (AL1) or 3 mg/kg (AL3) of alendronate or saline solution (CTL). After 60 days of drug therapy all animals were submitted to first lower molars extractions under general anesthesia. Operatory surgical time and the frequency of teeth fractures were measured as principal outcomes and indicators of surgical difficulty degree.

Results

Animals treated with alendronate (AL1 and AL3) were associated to higher operatory times and increased frequency of teeth fractures compared to match controls.

Conclusions

The bisphosphonate therapy may be associated with an increased surgical difficulty and trauma following simple exodontias protocols, which is considered a critical issue when it comes to osteonecrosis development.
Depletion of neutrophil extracellular traps in vivo results in hypersusceptibility to polymicrobial sepsis in mice
Authors: Meng Wei , Paunel-Görgülü Adnana , Flohé Sascha , Hoffmann Almuth , Witte Ingo , MacKenzie Colin , Baldus Stephan E , Windolf Joachim , Lögters Tim T
Published: July 2012

Introduction

Although the formation of neutrophil (PMN) extracellular traps (NETs) has been detected during infection and sepsis, their role in vivo is still unclear. This study was performed in order to evaluate the influence of NETs depletion by administration of recombinant human (rh)DNase on bacterial spreading, PMN tissue infiltration and inflammatory response in a mouse model of polymicrobial sepsis.

Methods

In a prospective controlled double-armed animal trial, polymicrobial sepsis was induced by cecal ligation and puncture (CLP). After CLP, mice were treated with rhDNase or phosphate buffered saline, respectively. Survival, colony forming unit (CFU) counts in the peritoneal cavity, lung, liver and blood were determined. PMN and platelet counts, IL-6 and circulating free (cf)-DNA/NETs levels were monitored. PMN infiltration, as well as organ damage, was analyzed histologically in the lungs and liver. Capability and capacity of PMN to form NETs were determined over time.

Results

cf-DNA/NETs were found to be significantly increased 6, 24, and 48 hours after CLP when compared to the levels determined in sham and naïve mice. Peak levels after 24 hours were correlated to enhanced capacity of bone marrow-derived PMN to form NETs after ex vivo stimulation with phorbol-12-myristate-13-acetate at the same time. rhDNase treatment of mice resulted in a significant reduction of cf-DNA/NETs levels 24 hours after CLP (P < 0.001). Although overall survival was not affected by rhDNase treatment, median survival after 24 hours was significantly lower when compared with the CLP group (P < 0.01). In mice receiving rhDNase treatment, CFU counts in the lung (P < 0.001) and peritoneal cavity (P < 0.05), as well as serum IL-6 levels (P < 0.001), were found to be already increased six hours after CLP. Additionally, enhanced PMN infiltration and tissue damage in the lungs and liver were found after 24 hours. In contrast, CFU counts in mice without rhDNase treatment increased later but more strongly 24 hours after CLP (P < 0.001). Similarly, serum IL-6 levels peaked after 24 hours (P < 0.01).

Conclusions

This study shows, for the first time, that depletion of NETs by rhDNase administration impedes the early immune response and aggravates the pathology that follows polymicrobial sepsis in vivo.
Canonical Wnt signaling regulates smooth muscle precursor development in the mouse ureter
Authors: Trowe Mark-Oliver , Airik Rannar , Weiss Anna-Carina , Farin Henner F. , Foik Anna B. , Bettenhausen Eva , Schuster-Gossler Karin , Taketo Makoto Mark , Kispert Andreas
Published: July 2012

Smooth muscle cells (SMCs) are a key component of many visceral organs, including the ureter, yet the molecular pathways that regulate their development from mesenchymal precursors are insufficiently understood. Here, we identified epithelial Wnt7b and Wnt9b as possible ligands of Fzd1-mediated β-catenin (Ctnnb1)-dependent (canonical) Wnt signaling in the adjacent undifferentiated ureteric mesenchyme. Mice with a conditional deletion of Ctnnb1 in the ureteric mesenchyme exhibited hydroureter and hydronephrosis at newborn stages due to functional obstruction of the ureter. Histological analysis revealed that the layer of undifferentiated mesenchymal cells directly adjacent to the ureteric epithelium did not undergo characteristic cell shape changes, exhibited reduced proliferation and failed to differentiate into SMCs. Molecular markers for prospective SMCs were lost, whereas markers of the outer layer of the ureteric mesenchyme fated to become adventitial fibroblasts were expanded to the inner layer. Conditional misexpression of a stabilized form of Ctnnb1 in the prospective ureteric mesenchyme resulted in the formation of a large domain of cells that exhibited histological and molecular features of prospective SMCs and differentiated along this lineage. Our analysis suggests that Wnt signals from the ureteric epithelium pattern the ureteric mesenchyme in a radial fashion by suppressing adventitial fibroblast differentiation and initiating smooth muscle precursor development in the innermost layer of mesenchymal cells.
Onecut transcription factors act upstream of Isl1 to regulate spinal motoneuron diversification
Authors: Roy Agnès , Francius Cédric , Rousso David L. , Seuntjens Eve , Debruyn Joke , Luxenhofer Georg , Huber Andrea B. , Huylebroeck Danny , Novitch Bennett G. , Clotman Frédéric
Published: July 2012

During development, spinal motoneurons (MNs) diversify into a variety of subtypes that are specifically dedicated to the motor control of particular sets of skeletal muscles or visceral organs. MN diversification depends on the coordinated action of several transcriptional regulators including the LIM-HD factor Isl1, which is crucial for MN survival and fate determination. However, how these regulators cooperate to establish each MN subtype remains poorly understood. Here, using phenotypic analyses of single or compound mutant mouse embryos combined with gain-of-function experiments in chick embryonic spinal cord, we demonstrate that the transcriptional activators of the Onecut family critically regulate MN subtype diversification during spinal cord development. We provide evidence that Onecut factors directly stimulate Isl1 expression in specific MN subtypes and are therefore required to maintain Isl1 production at the time of MN diversification. In the absence of Onecut factors, we observed major alterations in MN fate decision characterized by the conversion of somatic to visceral MNs at the thoracic levels of the spinal cord and of medial to lateral MNs in the motor columns that innervate the limbs. Furthermore, we identify Sip1 (Zeb2) as a novel developmental regulator of visceral MN differentiation. Taken together, these data elucidate a comprehensive model wherein Onecut factors control multiple aspects of MN subtype diversification. They also shed light on the late roles of Isl1 in MN fate decision.
DNA damage and neurotoxicity of chronic alcohol abuse
Authors: Kruman Inna I , Henderson George I , Bergeson Susan E
Published: July 2012

Chronic alcohol abuse results in a variety of pathological effects including damage to the brain. The causes of alcohol-induced brain pathology are presently unclear. Several mechanisms of pathogenicity of chronic alcoholism have been proposed, including accumulation of DNA damage in the absence of repair, resulting in genomic instability and death of neurons. Genomic instability is a unified genetic mechanism leading to a variety of neurodegenerative disorders. Ethanol also likely interacts with various metabolic pathways, including one-carbon metabolism (OCM). OCM is critical for the synthesis of DNA precursors, essential for DNA repair, and as a methyl donor for various methylation events, including DNA methylation. Both DNA repair and DNA methylation are critical for maintaining genomic stability. In this review, we outline the role of DNA damage and DNA repair dysfunction in chronic alcohol-induced neurodegeneration.
Bucking the trend: Poitier at the frontier
Authors: Barrett Jenny
Published: July 2012

Considering the privileged space that the western enjoyed in the twentieth century in the forging and endorsing of a certain kind of American national identity, this article argues that Poitier's presence as a frontier hero in some of the most overlooked and underestimated films of
the man's career is of remarkable significance. Despite the exasperation of some critics at the formulaic nature of his three westerns, I will argue that the casting of Poitier as the westerner creates a disturbance in the construction of the on-screen American ancestor, raising vital issues
concerning American masculinity, racism, miscegenation and freedom.
RE/Searching Angry Women
Authors: Allmer Patricia
Published: July 2012

RE/Search’s issue on Angry Women brought together a range of critics, theorists, performance artists and lesbian activists including Kathy Acker, Valie Export, bell hooks, Lydia Lunch, Carolee Schneemann and Annie Sprinkle. Published in 1991, the issue proposed a ‘revolutionary
feminism’, finding its forms and manifestations in ‘wild sex, humor, beauty, spirituality plus radical politics’. Despite the radical content of this issue and the significance of its contributors for feminism, the publication has received little academic attention. Analyses
that address this publication treat it in isolation from the wider context of RE/Search and its theoretical perspectives. This article focuses on Angry Women by setting it into these contexts. It argues that RE/Search’s theoretical positions can be understood through Bataillean notions
of base materialism. The article explores a range of influences and relations, including that of Bataille on RE/Search and the significance of the relation of Angry Women to the wider RE/Search project once read through the lens of Bataillean theories. It will also demonstrate that the deliberate
selection of contributors by Juno and Vale reveals a distinct Bataillean strain within feminist projects in the 1990s.
The new 'porno-chic'? Fashion, consumption and film pornography
Authors: KIRKHAM NEIL
Published: July 2012

This article studies the emerging links between fashion, consumption and film pornography. Drawing on recent work on the 'pornification' of popular culture, it situates its discussion around the ongoing influence of pornography on mainstream consumer culture and the emergence of branded
consumer goods from the American pornographic film industry. It considers recent controversy concerning the impact on pornography on the style and appearance of young western women but also develops these ideas around an analysis of both how American pornographic films sell related product
such as T-shirts, baseball caps and sweatshirts as well as how the mise-en-scène of these texts is customized in order to accommodate such marketing strategies.

Reference is made to Playboy, Hustler and Vivid Video, but the central case study is an analysis of the role of less-established
American production companies such as Anabolic Video in creating and commodifying their products in a range of ways beyond the basic manufacture of hard-core pornographic films. This is located alongside other companies that draw on the transgressive appeal of pornography past and present
as a way to differentiate their products (the 'Porn Star' clothing range and the use of soft-core pornographic techniques and hard-core performers in the marketing campaigns of American Apparel).
The Knock-and-Announce Rule and Police Searches after Hudson v. Michigan
Authors: Totten Christopher , (Cheurprakobkit) Sutham Cobkit
Published: July 2012

The exclusionary rule in the Fourth Amendment knock-and-announce context has been challenged by the U.S. Supreme Court in Hudson v. Michigan. After Hudson, even if police fail to knock and announce prior to entering a person's home to search, any evidence found by police remains admissible at that person's trial. The Court reasoned that today police are better educated, trained, disciplined, and monitored by citizens; as a result, exclusion of evidence is no longer needed as a deterrent for police knock-and-announce misconduct during searches. This paper, using both legal and social scientific methodologies, examines the legitimacy of this aspect of the Court's reasoning by surveying chiefs in large U.S. cities concerning their perceptions of the efficacy and value of the various deterrents to knock-and-announce misconduct (e.g., exclusion, education, training, discipline, and citizen review). The study also surveys the chiefs on their departmental policies and procedures related to the knock-and-announce rule and police searches as well as their knowledge of the rule. The study's outcomes reflected in the paper enhance understanding of the efficacy of the exclusionary rule compared to the alternative deterrents for police knock-and-announce violations during searches.
Hungarian Diet and Nutritional Status Survey – The OTAP2009 study. V. Microelement intake of the Hungarian population
Authors: Lugasi Andrea , Sarkadi Nagy Eszter , Zentai Andrea , Bakacs Márta , Illés Éva , Baldauf Zsolt , Martos Éva
Published: July 2012

For a healthy status the adequate intake of microelements is vital. Aim and method: The Hungarian Diet and Nutritional Status Survey – joining to the European Health Interview Survey – studied the dietary habits of the Hungarian population. The present paper demonstrates the microelement intake. Results: While the intake of iron, copper and zinc was sufficient in males, it was deficient in females according to the Hungarian recommendations. Especially women in their reproductive age ingested iron below the recommendation, thus representing a health risk. In comparison to earlier Hungarian data, zinc and chromium intake decreased unfavorable. Conclusions: Since in Hungary the consumption of the whole grain products with high trace element content is traditionally low, as also reflected in the present study, it would be desirable to increase the contribution of these foods in the diet in order to enhance the intake of microelements. Orv. Hetil., 2012, 153, 1177–1184.
Diagnostic delay of rare diseases in Europe and in Hungary
Authors: Földvári Anett , Szy Ildikó , Sándor János , Pogány Gábor , Kosztolányi György
Published: July 2012

The long diagnostic delay is a characteristic problem of rare disease patients. Aims: Diagnostic delay was studied in 14 countries by EurordisCare2 involving patient organizations. Methods: 252 Hungarian patients (cystic fibrosis; Duchenne muscular dystrophy; tuberous sclerosis, retinitis pigmentosa, and Williams’ syndrome) completed the questionnaires. Results: The median delay was longer in Hungary than in Europe (cystic fibrosis: 227 vs. 45 days; Duchenne muscular dystrophy: 467 vs. 360 days; tuberous sclerosis: 155 vs. 120 days). Patients’ experience was similar in Hungary and in Europe. The proportion of misdiagnosis was 30.8% in Hungary (Europe: 41%), 34.8% of patients got diagnosis outside of living place region (EU: 26%) and 19.9% of them found the personal expenses too high (EU: 10%). Delivery of the diagnosis was unnecessary according to 27.4% of Hungarian patients (EU: 35%). Conclusions: The qualitative survey demonstrated that the problems with the diagnosis of rare diseases are widespread, the identified areas require interventions, and it confirmed the importance of centralized care. Orv. Hetil., 2012, 153, 1185–1190.
Diffusion-weighted MR imaging; the importance of ADC and perfusion values in the differential diagnosis of pancreatic adenocarcinoma and mass forming pancreatitis
Authors: Puskás Tamás , Henits Imre
Published: July 2012

Despite the increasing diagnostic accuracy of cross sectional imaging modalities, the correct differentiation between pancreatic adenocarcinoma and mass forming pancreatitis has remained a challenge. Aim: Based on their 2 and ½ -year experience, the aim of the authors was to assess the clinical utility of diffusion-weighted magnetic resonance imaging in the diagnosis and discernment of pancreatic adenocarcinoma and mass forming pancreatitis. Methods: 3 b-values diffusion-weighted magnetic resonance examinations were performed in 19 patients suffering from adenocarcinoma and in 8 patients with pancreatitis. 12 healthy patients were examined as reference. Apparent diffusion coefficient and perfusion values were calculated. Malignancy was verified by pathology in all cases. An inflammatory disease was diagnosed on the basis of previous medical history, changes in laboratory values, follow-up computer tomographic examinations and improvement in the patients’ condition. Results: Comparison of the apparent diffusion coefficient and perfusion values revealed significant differences between healthy pancreatic tissues and those affected by inflammation or tumor. The highest apparent diffusion coefficient and perfusion values were detected in the normal pancreas. Mass forming pancreatitis had diminished the apparent diffusion coefficient and perfusion values, whereas these values were the lowest in tumorous tissues. Conclusion: In agreement with literature data, the authors conclude that diffusion-weighted magnetic resonance imaging is a promising differential-diagnostic imaging tool in the distinction of circumscribed pancreatic lesions. Orv. Hetil., 2012, 153, 1191–1196.
Uterine Leiomyosarcoma in Asian Patients: Validation of the Revised Federation of Gynecology and Obstetrics Staging System and Identification of Prognostic Classifiers
Authors: Tan Pei-Shan , Koh Elisa , Pang Cindy , Ong Whee-Sze , Ngo Lynette , Soh Lay-Tin , Quek Richard , Chay Wen-Yee , Ho Tew-Hong , Tay Sun-Kuie , Chew Sung-Hock , Lim-Tan Soo-Kim , Khoo-Tan Hs , Lim Sheow Lei , Busmanis Inny , Goh Liang Kee , Chia Yin-Nin , Chia Whay-Kuang , Lim Timothy
Published: July 2012

Learning Objectives

After completing this course, the reader will be able to: Compare concordance indices of the older and the revised FIGO staging systems.Identify gaps in the current FIGO staging system.

CME This article is available for continuing medical education credit at CME.TheOncologist.com

Background.

In 2008, the Federation of Gynecology and Obstetrics (FIGO) revised their 1988 staging system for uterine leiomyosarcomas. In this article, we compare performance of the 2008 and 1988 FIGO systems.

Methods.

Individual case data were manually culled. Staging was retrospectively assessed according to revised and 1998 FIGO criteria. Overall survival distribution was assessed by the Kaplan-Meier method. Harrell's concordance index was used to assess the discriminative ability of a fitted Cox model to predict overall survival.

Results.

A total of 110 cases of uterine leiomyosarcomas were reviewed and data from 88 patients were analyzed. In all, 71% of cases were classified as stage I, 7% as stage II, 3% as stage III, and 19% as stage IV under the revised FIGO staging system. Nine patients (10.2%) were downstaged and none were upstaged. The revised FIGO system did not show a significant improvement over the 1988 FIGO system in the ability to discriminate the risk of death of patients between stages, with concordance indexes of 0.70 and 0.71, respectively. Most patients were classified as stage I with age, tumor grade, tumor size, and lymphovascular invasion as prognostic factors.

Conclusion.

The 2008 revised FIGO staging system for uterine leiomyosarcomas does not perform better than the 1988 system for uterine endometrial carcinomas. A better staging system is needed for these cases.
Methods of graphing several variables
Authors: McIntosh J. D.
Published: July 2012

Summary:

A description is given of methods of plotting experimental values of more than two variables in such a way that relationships between each pair of variables can be established taking all experimental values into account; these methods are illustrated by examples taken from concrete research. Their use permits a considerable reduction in the amount of experimental work involved in examining the effects of several variables on a particular property.
Theoretical and Experimental Models of Hormetic Fusion Tubulogenesis
Authors: Fosslien Egil
Published: July 2012

Hormetic morphogens are morphogens such as transforming growth factor beta (TGF-β) in mammals and auxin in plants that induce hormetic responses. For example, in vitro, TGF-β stimulates and inhibits cell proliferation at low and high concentrations respectively. I developed a model of hormetic morphogen gradient control of the morphogenesis of the fusion of bilateral aortic precursors (Anlagen) that form the aorta during development; and validated the model with findings obtained by Daucus Carota fusion experiments. Theoretically, radial concentration gradients of a hormetic morphogen can form hollow (vessels) or solid ( Carota) tubular structures. In arteries, blood flow and pressure can shape mural gradients and determine wall curvature and thereby vessel diameter. As Anlagen grow they form a temporary common wall that is subsequently removed, which results in fusion of the Anlagen lumina and an aorta with a lumen diameter that accommodates the combined blood flow to the iliac arteries. Carota seedlings grown close together exhibited proximally fused root cones, serial cross-sections of which exhibited coaxial fusion patterns that closely resembled the predicted vascular fusion patterns, thus validating a role for hormesis and hormetic morphogens in the morphogenesis of the aorta and possibly the morphogenesis of other human midline structures.
Field emission - based many-valued processing using carbon nanotube controlled switches - Part 1: Fundamentals
Authors: Al-Rabadi Anas , Mousa Marwan
Published: July 2012

In this first part of the article, basics of field emission will be presented
which will be utilized within the second part of the article for the
architecture effectuation of new Carbon Nanotube (CNT) - based controlled
nano switches. To implement the field emission CNT - based controlled switch,
four field emission CNTs that have single carbon nanotubes as the emitters
were tested; two with single-walled CNT and two with multiwalled CNT. A tube
with a tungsten tip was also used for comparison. The Fowler- Nordheim
analysis of the DC current-voltage data provided reasonable values for the
sizes and local fields of emitters. It is also shown within the new
implementation of the controlled switch that square-wave pulses from a single
laser diode with 20 mW power and 658 nm wavelength which is focused on each
emitter increased the emitted current by 5.2% with the CNT and 0.19% with the
compared tungsten tip.