bluuebunny/crossref_metadata_2025 huggingface dataset:
Involving Men in Efforts to End Violence Against Women
Authors: Flood Michael
Published: August 2011

Around the world, there are growing efforts to involve boys and men in the prevention of violence against women: as participants in education programs, as targets of social marketing campaigns, as policy makers and gatekeepers, and as activists and advocates. Efforts to prevent violence against girls and women now increasingly take as given that they must engage men. While there are dangers in doing so, there also is a powerful feminist rationale for such work. This article provides a review of the variety of initiatives, which engage or address men to prevent violence against women. It maps such efforts, locating them within a spectrum of prevention activities. Furthermore, the article identifies or advocates effective strategies in work with men to end violence against women.
‘‘Gay’’ Sidekicks: Queer Anxiety and the Narrative Straightening of the Superhero
Authors: Shyminsky Neil
Published: August 2011

In comic book and movie narratives that are dominated by figures of heroic masculinity, the male superhero sidekick is typically a sexually ambiguous character who performs alternative modes of masculinity. This article argues that these alternative masculinities serve primarily to obscure the anxiety that is endemic to the superhero’s own problematic identity and sexuality, effectively ‘‘straightening’’ the central narrative and preserving the superhero as a beacon of heteronormativity by projecting queer desire or fear entirely on to the ‘‘gay’’ sidekick. Ironically, the seemingly straightened primary narrative—and hero—remains beholden to the same ‘‘gay’’ sidekick that it marginalizes. The efficacy of these sidekicks is further discussed and detailed with specific reference to the popular superhero sidekicks Robin (sidekick to Batman) and Jimmy Olsen (sidekick to Superman).
Application of the 2010 McDonald criteria for the diagnosis of multiple sclerosis in a Spanish cohort of patients with clinically isolated syndromes
Authors: Gómez-Moreno M , Díaz-Sánchez M , Ramos-González A
Published: August 2011

Background: Recently the International Panel on Diagnosis of Multiple Sclerosis (MS) has proposed new magnetic resonance imaging (MRI) criteria for the diagnosis of MS in patients with clinically isolated syndromes (CIS). We aimed to evaluate the accuracy of these new criteria for lesions dissemination in space (DIS) and time (DIT), from a single MRI scan, to predict conversion from CIS to clinically definite MS.

Methods: We studied 67 CIS patients with baseline MRI performed within the first 3 months after onset. The follow-up was of at least 24 months. The sensitivity, specificity and accuracy of Barkhof–Tintoré criteria and the new proposed MRI criteria for DIS and DIT were calculated with SPSS v.15.0.

Results: The mean age for clinical onset was 30 years and 64% of patients were female. The overall conversion rate was 74%. In our cohort, Barkhof–Tintoré criteria showed a sensitivity of 71.43%, a specificity of 66.67%, with an accuracy of 73.1%. New DIS criteria showed a sensitivity of 85.71%, a specificity of 64.71% and an accuracy of 80.30%. We also evaluated the new DIT criteria with a single MRI scan in 54 patients with baseline scans that included gadolinium-enhanced images. The sensitivity of the test was 52.63% with a specificity of 75.00% and an accuracy of 59.26%.

Conclusion: New DIS criteria are simpler and more sensitive than previous criteria. The sensitivity of DIT criterion using a single MRI scan was rather low, as other previous studies showed, reflecting its stringency, but it could improve the accuracy of early MS diagnosis in that group of patients with typical CIS and gadolinium-enhancing and non-enhancing lesions on their baseline scans. These results reinforce their use in MS diagnosis.
Visual dysfunction in multiple sclerosis correlates better with optical coherence tomography derived estimates of macular ganglion cell layer thickness than peripapillary retinal nerve fiber layer thickness
Authors: Saidha Shiv , Syc Stephanie B. , Durbin Mary K. , Eckstein Christopher , Oakley Jonathan D. , Meyer Scott A. , Conger Amy , Frohman Teresa C. , Newsome Scott , Ratchford John N. , Frohman Elliot M. , Calabresi Peter A.
Published: August 2011

Background: Post-mortem analyses of multiple sclerosis (MS) eyes demonstrate prominent retinal neuronal ganglion cell layer (GCL) loss, in addition to related axonal retinal nerve fiber layer (RNFL) loss. Despite this, clinical correlations of retinal neuronal layers remain largely unexplored in MS.

Objectives: To determine if MS patients exhibit in vivo retinal neuronal GCL loss, deeper retinal neuronal loss, and investigate correlations between retinal layer thicknesses, MS clinical subtype and validated clinical measures.

Methods: Cirrus HD-optical coherence tomography (OCT), utilizing automated intra-retinal layer segmentation, was performed in 132 MS patients and 78 healthy controls. MS classification, Expanded Disability Status Scale (EDSS) and visual function were recorded in study subjects.

Results: GCL+inner plexiform layer (GCIP) was thinner in relapsing–remitting MS (RRMS; n = 96, 71.6 µm), secondary progressive MS (SPMS; n = 20, 66.4 µm) and primary progressive MS (PPMS; n = 16, 74.1 µm) than in healthy controls (81.8 µm; p < 0.001 for all). GCIP thickness was most decreased in SPMS, and although GCIP thickness correlated significantly with disease duration, after adjusting for this, GCIP thickness remained significantly lower in SPMS than RRMS. GCIP thickness correlated significantly, and better than RNFL thickness, with EDSS, high-contrast, 2.5% low-contrast and 1.25% low-contrast letter acuity in MS. 13.6% of patients also demonstrated inner or outer nuclear layer thinning.

Conclusions: OCT segmentation demonstrates in vivo GCIP thinning in all MS subtypes. GCIP thickness demonstrates better structure-function correlations (with vision and disability) in MS than RNFL thickness. In addition to commonly observed RNFL/GCIP thinning, retinal inner and outer nuclear layer thinning occur in MS.
Treatment of relapsing–remitting multiple sclerosis with high-dose cyclophosphamide induction followed by glatiramer acetate maintenance
Authors: Harrison Daniel M , Gladstone Douglas E , Hammond Edward , Cheng Jeffrey , Jones Richard J , Brodsky Robert A , Kerr Douglas , McArthur Justin C , Kaplin Adam
Published: August 2011

Background: Previous studies have described stabilization of aggressive multiple sclerosis (MS) with one-time induction therapy with high-dose cyclophosphamide (HiCy). The long-term benefit of this stabilization followed by conventional therapy has not been explored.

Objective: The objective of this study was to evaluate the safety and clinical outcomes following treatment of relapsing–remitting MS with HiCy induction therapy followed by glatiramer acetate maintenance.

Methods: A retrospective review of a closely followed population of thirty two MS patients treated with HiCy (200mg/kg intravenous infusion over 4 days) followed by maintenance with glatiramer acetate was performed.

Results: Annualized relapse rate was reduced from 1.37 in the 2 years prior to treatment to 0.27 over a mean post-treatment follow-up period of 14 months (range 0.5–33.8). The projected probability of relapse-free survival at 2 years was 0.64 (95% CI 0.37–0.82). The projected probability of Expanded Disability Status Scale (EDSS) progression-free survival at 2 years was 0.77 (95% CI 0.43–0.92). The mean number of gadolinium-enhanced lesions was reduced from 0.86 (SD 1.6) at baseline to 0 at 12 months and 0.08 (SD 0.28) at 15–24 months. A total of 55% of patients had no evidence of disease activity in follow-up. Infectious complications occurred in 47% with no long-term morbidity and no deaths.

Conclusions: Induction therapy with HiCy followed by long-term maintenance with glatiramer acetate is well tolerated in patients with MS, and appears to be efficacious in reducing the risk of relapse, disability progression, and new MRI lesions.
Efficacy of EZStep in the Management of Plantar Fasciitis
Authors: Al-Bluwi Mohammed T. , Sadat-Ali Mir , Al-Habdan Ibrahim M. , Azam Mohammed Q.
Published: August 2011

Plantar fasciitis is one of the most common causes of heel pain. Despite extensive efforts foot surgeons continue to debate the best modality of treatment. Analgesics, shoe inserts, stretching exercises, steroid injection, night splints, and extracorporeal shock wave therapy have proved effective in one group but fail in others. This study evaluated the efficacy of EZStep, a new foot brace for the management of plantar fasciitis. A total of 198 patients were randomized in 2 groups; group 1 (study group) received nonsteroidal anti-inflammatory drugs (NSAIDs; 4-6 weeks) and EZStep whereas group 2 (control group) received either NSAID and physiotherapy alone (2A) or NSAID, physiotherapy, and local steroid injection (2B). None of the patients received over-the-counter insoles or strapping of plantar arch to avoid any bias in randomization. Evaluations included measurement of weight and height, visual analog scale (VAS) for pain, and Short-Form McGill Pain Questionnaire (SFMPQ). After 8 weeks, patients were reevaluated, and assessment for the VAS and SFMPQ with treatment outcome was performed. Patients with VAS scores ≤3 were considered as excellent, ≥4 as good, and ≥7 as poor. The posttreatment evaluation showed that VAS scores were in the range from 2.97 ± 1.06 to 7.64 ± 2.9 (2A), P = .001, 95% confidence interval (CI) <−4.104; for 2B P = .001, CI <−2.44, and SFMPQ was 21.7 ± 4.5 and 69.2 ± 5.8 (group 2A; P = .001, 95% CI <−46.44). Compared with group 2B the SFMPQ was 66.5 ± 4.3 ( P = .001, 95% CI <−30.720). In group 1 as per VAS, 86 (73.5%) were evaluated as excellent, 15 (12.8%) as good, and 16 (13.6%) as poor. Our study shows that the regular use of EZStep with short course of NSAIDs (4-6 weeks) was effective in ameliorating symptoms in more than 85% of patients suffering from plantar fasciitis.
The ANNSERS (Antipsychotic Non-Neurological Side Effects Rating Scale): validation of sexual side-effect measurement
Authors: Mahmoud Ahmed , Drake Richard J. , Lewis Shôn W. , Hayhurst Karen P. , Barnes Thomas R. E.
Published: August 2011

Antipsychotic nonneurological side effects, such as sexual dysfunction, can adversely affect the quality of patients’ relationships, their treatment adherence and their quality of life. In the UK CUtLASS (Cost Utility of the Latest Antipsychotics in Severe Schizophrenia) study, nonneurological side effects were assessed using the ANNSERSv1 (Antipsychotic Non-Neurological Side Effects Rating Scale version 1), a new scale to assess the side effects associated with both first- and second-generation antipsychotic drugs. A total of 26 participants also completed the Derogatis Interview for Sexual Functioning (self-report version, DISF-SR). A statistically significant, and specific, correlation was found between scores on the DISF-SR and the sexual side-effect section of the ANNSERS at baseline. The sexual side-effects subscale of the ANNSERS is a valid measure of sexual dysfunction in the treatment of schizophrenia.
Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL)
Authors: Ralfkiaer Ulrik , Hagedorn Peter H. , Bangsgaard Nannie , Løvendorf Marianne B. , Ahler Charlotte B. , Svensson Lars , Kopp Katharina L. , Vennegaard Marie T. , Lauenborg Britt , Zibert John R. , Krejsgaard Thorbjørn , Bonefeld Charlotte M. , Søkilde Rolf , Gjerdrum Lise M. , Labuda Tord , Mathiesen Anne-Merete , Grønbæk Kirsten , Wasik Mariusz A. , Sokolowska-Wojdylo Malgorzata , Queille-Roussel Catherine , Gniadecki Robert , Ralfkiaer Elisabeth , Geisler Carsten , Litman Thomas , Woetmann Anders , Glue Christian , Røpke Mads A. , Skov Lone , Odum Niels
Published: August 2011

Cutaneous T-cell lymphomas (CTCLs) are the most frequent primary skin lymphomas. Nevertheless, diagnosis of early disease has proven difficult because of a clinical and histologic resemblance to benign inflammatory skin diseases. To address whether microRNA (miRNA) profiling can discriminate CTCL from benign inflammation, we studied miRNA expression levels in 198 patients with CTCL, peripheral T-cell lymphoma (PTL), and benign skin diseases (psoriasis and dermatitis). Using microarrays, we show that the most induced (miR-326, miR-663b, and miR-711) and repressed (miR-203 and miR-205) miRNAs distinguish CTCL from benign skin diseases with > 90% accuracy in a training set of 90 samples and a test set of 58 blinded samples. These miRNAs also distinguish malignant and benign lesions in an independent set of 50 patients with PTL and skin inflammation and in experimental human xenograft mouse models of psoriasis and CTCL. Quantitative (q)RT-PCR analysis of 103 patients with CTCL and benign skin disorders validates differential expression of 4 of the 5 miRNAs and confirms previous reports on miR-155 in CTCL. A qRT-PCR–based classifier consisting of miR-155, miR-203, and miR-205 distinguishes CTCL from benign disorders with high specificity and sensitivity, and with a classification accuracy of 95%, indicating that miRNAs have a high diagnostic potential in CTCL.
Enzymatic synthesis of long double-stranded DNA labeled with haloderivatives of nucleobases in a precisely pre-determined sequence
Authors: Sobolewski Ireneusz , Polska Katarzyna , Żylicz-Stachula Agnieszka , Jeżewska-Frąckowiak Joanna , Rak Janusz , Skowron Piotr
Published: August 2011

Background

Restriction endonucleases are widely applied in recombinant DNA technology. Among them, enzymes of class IIS, which cleave DNA beyond recognition sites, are especially useful. We use BsaI enzyme for the pinpoint introduction of halogen nucleobases into DNA. This has been done for the purpose of anticancer radio- and phototherapy that is our long-term objective.

Results

An enzymatic method for synthesizing long double-stranded DNA labeled with the halogen derivatives of nucleobases (Hal-NBs) with 1-bp accuracy has been put forward and successfully tested on three different DNA fragments containing the 5-bromouracil (5-BrU) residue. The protocol assumes enzymatic cleavage of two Polymerase-Chain-Reaction (PCR) fragments containing two recognition sequences for the same or different class IIS restriction endonucleases, where each PCR fragment has a partially complementary cleavage site. These sites are introduced using synthetic DNA primers or are naturally present in the sequence used. The cleavage sites are not compatible, and therefore not susceptible to ligation until they are partially filled with a Hal-NB or original nucleobase, resulting in complementary cohesive end formation. Ligation of these fragments ultimately leads to the required Hal-NB-labeled DNA duplex. With this approach, a synthetic, extremely long DNA fragment can be obtained by means of a multiple assembly reaction (n × maximum PCR product length: n × app. 50 kb).

Conclusions

The long, precisely labeled DNA duplexes obtained behave in very much the same manner as natural DNA and are beyond the range of chemical synthesis. Moreover, the conditions of synthesis closely resemble the natural ones, and all the artifacts accompanying the chemical synthesis of DNA are thus eliminated. The approach proposed seems to be completely general and could be used to label DNA at multiple pre-determined sites and with halogen derivatives of any nucleobase. Access to DNAs labeled with Hal-NBs at specific position is an indispensable condition for the understanding and optimization of DNA photo- and radio-degradation, which are prerequisites for clinical trials of Hal-NBs in anticancer therapy.
Experimental annotation of post-translational features and translated coding regions in the pathogen Salmonella Typhimurium
Authors: Ansong Charles , Tolić Nikola , Purvine Samuel O , Porwollik Steffen , Jones Marcus , Yoon Hyunjin , Payne Samuel H , Martin Jessica L , Burnet Meagan C , Monroe Matthew E , Venepally Pratap , Smith Richard D , Peterson Scott N , Heffron Fred , McClelland Michael , Adkins Joshua N
Published: August 2011

Background

Complete and accurate genome annotation is crucial for comprehensive and systematic studies of biological systems. However, determining protein-coding genes for most new genomes is almost completely performed by inference using computational predictions with significant documented error rates (> 15%). Furthermore, gene prediction programs provide no information on biologically important post-translational processing events critical for protein function.

Results

We experimentally annotated the bacterial pathogen Salmonella Typhimurium 14028, using "shotgun" proteomics to accurately uncover the translational landscape and post-translational features. The data provide protein-level experimental validation for approximately half of the predicted protein-coding genes in Salmonella and suggest revisions to several genes that appear to have incorrectly assigned translational start sites, including a potential novel alternate start codon. Additionally, we uncovered 12 non-annotated genes missed by gene prediction programs, as well as evidence suggesting a role for one of these novel ORFs in Salmonella pathogenesis. We also characterized post-translational features in the Salmonella genome, including chemical modifications and proteolytic cleavages. We find that bacteria have a much larger and more complex repertoire of chemical modifications than previously thought including several novel modifications. Our in vivo proteolysis data identified more than 130 signal peptide and N-terminal methionine cleavage events critical for protein function.

Conclusion

This work highlights several ways in which application of proteomics data can improve the quality of genome annotations to facilitate novel biological insights and provides a comprehensive proteome map of Salmonella as a resource for systems analysis.
A rapid in situ procedure for determination of bacterial susceptibility or resistance to antibiotics that inhibit peptidoglycan biosynthesis
Authors: Santiso Rebeca , Tamayo María , Gosálvez Jaime , Bou Germán , Fernández María del Carmen , Fernández José Luis
Published: August 2011

Background

Antibiotics which inhibit bacterial peptidoglycan biosynthesis are the most widely used in current clinical practice. Nevertheless, resistant strains increase dramatically, with serious economic impact and effects on public health, and are responsible for thousands of deaths each year. Critical clinical situations should benefit from a rapid procedure to evaluate the sensitivity or resistance to antibiotics that act at the cell wall. We have adapted a kit for rapid determination of bacterial DNA fragmentation, to assess cell wall integrity.

Results

Cells incubated with the antibiotic were embedded in an agarose microgel on a slide, incubated in an adapted lysis buffer, stained with a DNA fluorochrome, SYBR Gold and observed under fluorescence microscopy. The lysis affects the cells differentially, depending on the integrity of the wall. If the bacterium is susceptible to the antibiotic, the weakened cell wall is affected by the lysing solution so the nucleoid of DNA contained inside the bacterium is released and spread. Alternatively, if the bacterium is resistant to the antibiotic, it is practically unaffected by the lysis solution and does not liberate the nucleoid, retaining its normal morphological appearance. In an initial approach, the procedure accurately discriminates susceptible, intermediate and resistant strains of Escherichia coli to amoxicillin/clavulanic acid. When the bacteria came from an exponentially growing liquid culture, the effect on the cell wall of the β-lactam was evident much earlier that when they came from an agar plate. A dose-response experiment with an E. coli strain susceptible to ampicillin demonstrated a weak effect before the MIC dose. The cell wall damage was not homogenous among the different cells, but the level of damage increased as dose increased with a predominant degree of effect for each dose. A microgranular-fibrilar extracellular background was evident in gram-negative susceptible strains after β-lactam treatment. This material was digested by DNase I, hybridised with a specific whole genome probe, and so recognized as DNA fragments released by the bacteria. Finally, 46 clinical strains from eight gram-negative and four gram-positive species were evaluated blind for susceptibility or resistance to one of four different β-lactams and vancomycin, confirming the applicability of the methodology.

Conclusion

The technique to assess cell wall integrity appears to be a rapid and simple procedure to identify resistant and susceptible strains to antibiotics that interfere with peptidoglycan biosynthesis.
A questionnaire to measure melanoma risk, knowledge and protective behaviour: Assessing content validity in a convenience sample of Scots and Australians
Authors: Gillespie Helen S , Watson Tony , Emery Jon D , Lee Amanda J , Murchie Peter
Published: August 2011

Background

The aim of this study was to assess the content validity of a questionnaire to measure melanoma risk, knowledge and protective behaviour in a convenience sample of Scots and Australians. Australia has the highest melanoma incidence worldwide but has developed a culture of skin cancer avoidance with a long history of skin cancer primary prevention campaigns of proven effectiveness. Scotland has lower incidence, but has shown a greater rate of increase between 1985 and 2007. There is an urgent need in Scotland, therefore, to identify those groups at greatest risk and provide them with effective preventative advice.

Method

A self-administered postal survey was completed by four groups formed from convenience samples in two geographical locations (Northeast Scotland and Western Australia). In univariate analysis scores on personal risk, level of concern, protective behaviour, and knowledge were compared by nationality, previous skin cancer diagnosis and personally knowing someone with melanoma. Multivariate linear regression analysis modelled the influence of potential predictor variables upon each of the scores.

Results

540 people completed the questionnaire, 273 Scots (50.6%). 133 (24.6%) Scots and 83 (15.4%) Australians previously had melanoma or non-melanoma skin cancer, whilst 120 (22.2%) Scots and 190 (35.2%) Australians personally knew someone with melanoma. Australians had higher knowledge (p < 0.001), level of concern (p < 0.001) and protective behaviour (p < 0.001) scores than the Scottish. Australian nationality was the strongest independent predictor of a higher knowledge score (p < 0.001), followed by a previous skin cancer diagnosis (p = 0.003), personal knowledge of someone with melanoma (p = 0.011), female gender (p = 0.005) and higher education status (p < 0.001) (R

2

= 0.163).

Conclusion

The questionnaire detected higher levels of knowledge and skin cancer protective behaviours in Australians than in Scottish people. This was expected and supports the content validity of the questionnaire and its value as a future research tool in the Scottish population.
Pilot study on developing a decision support tool for guiding re-administration of chemotherapeutic agent after a serious adverse drug reaction
Authors: Loke Pei Yi , Chew Lita , Yap Chun Wei
Published: August 2011

Background

Currently, there are no standard guidelines for recommending re-administration of a chemotherapeutic drug to a patient after a serious adverse drug reaction (ADR) incident. The decision on whether to rechallenge the patient is based on the experience of the clinician and is highly subjective. Thus the aim of this study is to develop a decision support tool to assist clinicians in this decision making process.

Methods

The inclusion criteria for patients in this study are: (1) had chemotherapy at National Cancer Centre Singapore between 2004 to 2009, (2) suffered from serious ADRs, and (3) were rechallenged. A total of 46 patients fulfilled the inclusion criteria. A genetic algorithm attribute selection method was used to identify clinical predictors for patients' rechallenge status. A Naïve Bayes model was then developed using 35 patients and externally validated using 11 patients.

Results

Eight patient attributes (age, chemotherapeutic drug, albumin level, red blood cell level, platelet level, abnormal white blood cell level, abnormal alkaline phosphatase level and abnormal alanine aminotransferase level) were identified as clinical predictors for rechallenge status of patients. The Naïve Bayes model had an AUC of 0.767 and was found to be useful for assisting clinical decision making after clinicians had identified a group of patients for rechallenge. A platform independent version and an online version of the model is available to facilitate independent validation of the model.

Conclusion

Due to the limited size of the validation set, a more extensive validation of the model is necessary before it can be adopted for routine clinical use. Once validated, the model can be used to assist clinicians in deciding whether to rechallenge patients by determining if their initial assessment of rechallenge status of patients is accurate.
Early complications after biliary enteric anastomosis for benign diseases: A retrospective analysis
Authors: Zafar Syed Nabeel , Khan Muhammad Rizwan , Raza Rushna , Khan Muhammad N , Kasi Mahwash , Rafiq Ammar , Jamy Omer H
Published: August 2011

Background

Biliary-enteric anastomosis (BEA) is a common surgical procedure performed for the management of biliary obstruction or leakage that results from a variety of benign and malignant diseases. Complications following BEA are not rare. We aimed to determine the incidence and the factors associated with early complications occurring after BEA for benign diseases.

Methods

We reviewed the medical records of all patients who underwent BEA for benign diseases at our institution between January 1988 and December 2009. The primary outcome was early post operative complication. Logistic regression analysis was done to identify factors predicting the occurrence of complications.

Results

Records of 79 patients were reviewed. There were 34 (43%) males and 45 (57% females). Majority (53%) had choledocholithiasis with impacted stone or distal stricture, followed by traumatic injury to the biliary system (33%). Thirty-four patients (43%) underwent a hepaticojejunostomy, 19 patients (24%) underwent a choledochojejunostomy, and choledochoduodenostomy was performed in 26 patients (33%). Early complications occurred in 39 (49%) patients - 41% had local complications and 25% had systemic complications. Most frequent complications were wound infection (23%) and bile leak (10%). Four (5%) patients died. On multivariate analysis, low serum albumin level (odds ratio = 16, 95% CI = 1.14-234.6) and higher ASA levels (odds ratio = 7, 95% CI: 1.22-33.34) were the independent factors predicting the early complications following BEA.

Conclusions

Half of the patients who underwent BEA for benign diseases had complications in our population. This high incidence may be explained by the high incidence of hypoalbuminemia and the high-risk group who underwent operation.
Translation and manipulation of silicon nanomembranes using holographic optical tweezers
Authors: Oehrlein Stefan M , Sanchez-Perez Jose R , Jacobson RB , Flack Frank S , Kershner Ryan J , Lagally Max G
Published: August 2011

We demonstrate the use of holographic optical tweezers for trapping and manipulating silicon nanomembranes. These macroscopic free-standing sheets of single-crystalline silicon are attractive for use in next-generation flexible electronics. We achieve three-dimensional control by attaching a functionalized silica bead to the silicon surface, enabling non-contact trapping and manipulation of planar structures with high aspect ratios (high lateral size to thickness). Using as few as one trap and trapping powers as low as several hundred milliwatts, silicon nanomembranes can be rotated and translated in a solution over large distances.
On the regularity of the solution for the second initial boundary value problem for hyperbolic systems in domains with conical points
Authors: Hung Nguyen Manh , Anh Nguyen Thanh , Chuc Phung Kim
Published: August 2011

In this paper, we deal with the second initial boundary value problem for higher order hyperbolic systems in domains with conical points. We establish several results on the well-posedness and the regularity of solutions.
Gait training with partial body weight support during overground walking for individuals with chronic stroke: a pilot study
Authors: Sousa Catarina O , Barela José A , Prado-Medeiros Christiane L , Salvini Tania F , Barela Ana MF
Published: August 2011

Background

It is not yet established if the use of body weight support (BWS) systems for gait training is effective per se or if it is the combination of BWS and treadmill that improves the locomotion of individuals with gait impairment. This study investigated the effects of gait training on ground level with partial BWS in individuals with stroke during overground walking with no BWS.

Methods

Twelve individuals with chronic stroke (53.17 ± 7.52 years old) participated of a gait training program with BWS during overground walking, and were evaluated before and after the gait training period. In both evaluations, individuals were videotaped walking at a self-selected comfortable speed with no BWS. Measurements were obtained for mean walking speed, step length, stride length and speed, toe-clearance, durations of total double stance and single-limb support, and minimum and maximum foot, shank, thigh, and trunk segmental angles.

Results

After gait training, individuals walked faster, with symmetrical steps, longer and faster strides, and increased toe-clearance. Also, they displayed increased rotation of foot, shank, thigh, and trunk segmental angles on both sides of the body. However, the duration of single-limb support remained asymmetrical between each side of the body after gait training.

Conclusions

Gait training individuals with chronic stroke with BWS during overground walking improved walking in terms of temporal-spatial parameters and segmental angles. This training strategy might be adopted as a safe, specific and promising strategy for gait rehabilitation after stroke.
Exploiting bounded signal flow for graph orientation based on cause–effect pairs
Authors: Dorn Britta , Hüffner Falk , Krüger Dominikus , Niedermeier Rolf , Uhlmann Johannes
Published: August 2011

Background

We consider the following problem: Given an undirected network and a set of sender–receiver pairs, direct all edges such that the maximum number of "signal flows" defined by the pairs can be routed respecting edge directions. This problem has applications in understanding protein interaction based cell regulation mechanisms. Since this problem is NP-hard, research so far concentrated on polynomial-time approximation algorithms and tractable special cases.

Results

We take the viewpoint of parameterized algorithmics and examine several parameters related to the maximum signal flow over vertices or edges. We provide several fixed-parameter tractability results, and in one case a sharp complexity dichotomy between a linear-time solvable case and a slightly more general NP-hard case. We examine the value of these parameters for several real-world network instances.

Conclusions

Several biologically relevant special cases of the NP-hard problem can be solved to optimality. In this way, parameterized analysis yields both deeper insight into the computational complexity and practical solving strategies.
Coordinated increase in inhibitory and excitatory synapses onto retinal ganglion cells during development
Authors: Soto Florentina , Bleckert Adam , Lewis Renate , Kang Yunhee , Kerschensteiner Daniel , Craig Ann Marie , Wong Rachel OL
Published: August 2011

Background

Neuronal output is shaped by a balance of excitation and inhibition. How this balance is attained in the central nervous system during development is not well understood, and is complicated by the fact that, in vivo, GABAergic and glycinergic synaptogenesis precedes that of glutamatergic synapses. Here, we determined the distributions of inhibitory postsynaptic sites on the dendritic arbors of individual neurons, and compared their developmental patterns with that of excitatory postsynaptic sites. We focused on retinal ganglion cells (RGCs), the output neurons of the retina, which receive excitatory input from bipolar cells and inhibitory input from amacrine cells. To visualize and map inhibitory postsynaptic sites, we generated transgenic mice in which RGCs express fluorescently tagged Neuroligin 2 (YFP-NL2) under the control of the Thy1 promoter. By labeling RGC dendrites biolistically in YFP-NL2-expressing retinas, we were able to map the spatial distribution and thus densities of inhibitory postsynaptic sites on the dendritic arbors of individual large-field RGCs across ages.

Results

We demonstrate that YFP-NL2 is present at inhibitory synapses in the inner plexiform layer by its co-localization with gephyrin, the γ2 subunit of the GABAA receptor and glycine receptors. YFP-NL2 puncta were apposed to the vesicular inhibitory transmitter transporter VGAT but not to CtBP2, a marker of presynaptic ribbons found at bipolar cell terminals. Similar patterns of co-localization with synaptic markers were observed for endogenous NL2. We also verified that expression of YFP-NL2 in the transgenic line did not significantly alter spontaneous inhibitory synaptic transmission onto RGCs. Using these mice, we found that, on average, the density of inhibitory synapses on individual arbors increased gradually until eye opening (postnatal day 15). A small centro-peripheral gradient in density found in mature arbors was apparent at the earliest age we examined (postnatal day 8). Unexpectedly, the adult ratio of inhibitory/excitatory postsynaptic sites was rapidly attained, shortly after glutamatergic synaptogenesis commenced (postnatal day 7).

Conclusion

Our observations suggest that bipolar and amacrine cell synaptogenesis onto RGCs appear coordinated to rapidly attain a balanced ratio of excitatory and inhibitory synapse densities prior to the onset of visual experience.
Vitamin C and asthma in children: modification of the effect by age, exposure to dampness and the severity of asthma
Authors: Hemilä Harri , Al‐Biltagi Mohammed , Baset Ahmed A
Published: August 2011

Background

We previously found a significant benefit of vitamin C supplementation in asthmatic children.

Purpose

To test whether the effect of vitamin C on asthma is heterogeneous over the participant population.

Methods

Egyptian asthmatic children between 7 and 10 years of age (n = 60) were included in the cross‐over trial. They were administered 0.2 grams per day of vitamin C and placebo for separate 6‐week periods. The variation in the vitamin C effect on two clinically relevant outcomes was analyzed: the childhood asthma control test (C‐ACT), which measures the severity of asthma symptoms (the scale ranges from 0 to 27 points, < 20 points indicating unsatisfactory asthma control), and FEV1. We used linear modeling to examine the variation of the vitamin C effect in the subgroups.

Results

The effect of vitamin C on the C‐ACT was significantly modified by age and baseline C‐ACT levels. In the children aged 7.0‐8.2 years with a baseline C‐ACT of 18 to 19 points, vitamin C increased the C‐ACT score by 4.2 points (95% CI: 3.3‐5.3); whereas in the children aged 8.3‐10 years who had a baseline C‐ACT of 14 to 15 points, vitamin C increased the C‐ACT score by only 1.3 points (95% CI: 0.1‐2.5). The effect of vitamin C on the FEV1 levels was significantly modified by age and exposure to dampness. In the children aged 7.0‐8.2 years with no exposure to dampness, vitamin C increased the FEV1 level by 37% (95% CI: 34‐40%), whereas in the children aged 8.3‐10 years with exposure to dampness or mold in their bedroom more than one year prior to the study, vitamin C increased the FEV1 level by only 21% (95% CI: 18‐25%).

Conclusions

We found strong evidence that the effect of vitamin C on asthmatic children is heterogeneous. Further research is needed to confirm our findings and identify the groups of children who would receive the greatest benefit from vitamin C supplementation.
Aryl hydrocarbon receptor-dependent upregulation of Cyp1b1 by TCDD and diesel exhaust particles in rat brain microvessels
Authors: Jacob Aude , Hartz Anika MS , Potin Sophie , Coumoul Xavier , Yousif Salah , Scherrmann Jean-Michel , Bauer Björn , Declèves Xavier
Published: August 2011

Background

AhR activates the transcription of several target genes including CYP1B1. Recently, we showed CYP1B1 as the major cytochrome P450 (CYP) enzyme expressed in human brain microvessels. Here, we studied the effect of AhR activation by environmental pollutants on the expression of Cyp1b1 in rat brain microvessels.

Methods

Expression of AhR and Cyp1b1 was detected in isolated rat brain microvessels. AhR was immunovisualised in brain microvessel endothelial cells. The effect of AhR ligands on Cyp1b1 expression was studied using isolated brain microvessels after ex vivo and/or in vivo exposure to TCDD, heavy hydrocarbons containing diesel exhaust particles (DEP) or Δ9-tetrahydrocannabinol (Δ9-THC).

Results

After ex vivo exposure to TCDD (a highly potent AhR ligand) for 3 h, Cyp1b1 expression was significantly increased by 2.3-fold in brain microvessels. A single i.p. dose of TCDD also increased Cyp1b1 transcripts (22-fold) and Cyp1b1 protein (2-fold) in rat brain microvessels at 72 h after TCDD. Likewise, DEP treatment (in vivo and ex vivo) strongly induced Cyp1b1 protein in brain microvessels. DEP-mediated Cyp1b1 induction was inhibited by actinomycin D, cycloheximide, or by an AhR antagonist. In contrast, a sub-chronic in vivo treatment with Δ9-THC once daily for 7 seven days had no effect on Cyp1b1 expression

Conclusions

Our results show that TCDD and DEP strongly induced Cyp1b1 in rat brain microvessels, likely through AhR activation.
Lipodystrophies: Genetic and Acquired Body Fat Disorders
Authors: Garg Abhimanyu
Published: August 2011

Context:

Lipodystrophies are heterogeneous, genetic or acquired disorders characterized by selective loss of body fat and predisposition to insulin resistance. The extent of fat loss determines the severity of associated metabolic complications such as diabetes mellitus, hypertriglyceridemia, and hepatic steatosis.

Evidence Acquisition and Synthesis:

Both original and review articles were found via PubMed search reporting on clinical features and management of various types of lipodystrophies and were integrated with the author's knowledge of the field.

Conclusion:

The autosomal recessive congenital generalized lipodystrophy and autosomal dominant familial partial lipodystrophy (FPL) are the two most common types of genetic lipodystrophies. Mutations in AGPAT2, BSCL2, CAV1, and PTRF have been reported in congenital generalized lipodystrophy and in LMNA, PPARG, AKT2, and PLIN1 in FPL. CIDEC is the disease gene for autosomal recessive, FPL and LMNA and ZMPSTE24 for autosomal recessive, mandibuloacral dysplasia-associated lipodystrophy. Recently, an autosomal recessive autoinflammatory lipodystrophy syndrome was reported to be due to PSMB8 mutation. Molecular genetic bases of many rare forms of genetic lipodystrophies remain to be elucidated. The most prevalent subtype of acquired lipodystrophy currently occurs with prolonged duration of protease inhibitor-containing, highly-active antiretroviral therapy in HIV-infected patients. The acquired generalized and partial lipodystrophies are mainly autoimmune in origin and display complement abnormalities. Localized lipodystrophies occur due to drug or vaccine injections, pressure, panniculitis, and other unknown reasons. The current management includes cosmetic surgery and early identification and treatment of metabolic and other complications with diet, exercise, hypoglycemic drugs, and lipid-lowering agents.
Acute Decline in Serum Sclerostin in Response to PTH Infusion in Healthy Men
Authors: Yu Elaine W. , Kumbhani Ruchit , Siwila-Sackman Erica , Leder Benjamin Z.
Published: August 2011

Context:

Animal models suggest that the osteoblast-stimulating actions of PTH are mediated by acute suppression of sclerostin, an inhibitor of the anabolic Wnt pathway. The immediate physiological changes in serum sclerostin in response to PTH infusion have not been reported in human studies.

Objective:

We sought to determine the acute physiological effects of PTH infusion on serum sclerostin and bone turnover markers in healthy adult men.

Design, Setting, and Participants:

Fifty-three healthy adult men underwent an 18-h iv infusion of human PTH(1-34) at a dose of 0.55 U/kg · h.

Outcomes:

Serum levels of ionized calcium, sclerostin, and markers of bone formation (osteocalcin and amino-terminal propeptide of type I procollagen) and bone resorption (C-telopeptide and N-telopeptide) were obtained at 0, 6, 12, and 18 h.

Results:

Serum ionized calcium, C-telopeptide, and N-telopeptide increased, and osteocalcin and amino-terminal propeptide of type I procollagen fell linearly throughout the PTH infusion (P < 0.001 for all). Average ± sem sclerostin levels declined from 936 ± 65 to 813 ± 63 pg/ml at 6 h (P < 0.001) and remained stably suppressed for the duration of the PTH infusion. There were no significant correlations between change in sclerostin and change in bone markers.

Conclusions:

Serum sclerostin declined in response to acute PTH infusion within 6 h in healthy adult men. The early plateau in sclerostin suppression may indicate that maximal stimulation of the Wnt pathway is achieved quickly after exposure to PTH. Our findings support the hypothesis that PTH may mediate its anabolic effects in part via suppression of sclerostin.
Treatment of Androgen Excess in Adolescent Girls: Ethinylestradiol-Cyproteroneacetate Versus Low-Dose Pioglitazone-Flutamide-Metformin
Authors: Ibáñez Lourdes , Diaz Marta , Sebastiani Giorgia , Sánchez-Infantes David , Salvador Cristina , Lopez-Bermejo Abel , de Zegher Francis
Published: August 2011

Objective:

The aim was to perform a first comparison between the effects of a classic therapy and those of a novel treatment for androgen excess in adolescent girls.

Design and Setting:

We conducted a randomized, open-labeled trial at a university hospital.

Participants:

Thirty-four adolescents with hyperinsulinemic androgen excess and without risk of pregnancy participated in the study.

Interventions:

Ethinyl estradiol-cyproterone acetate (EE-CA) vs. a low-dose combination of pioglitazone, flutamide, and metformin (PioFluMet) was administered for 6 months.

Main Outcome Measures:

We assessed hirsutism and acne scores; androgen excess; fasting insulin, lipid profile, C-reactive protein, high molecular-weight adiponectin, leptin, follistatin; carotid intima-media thickness; body composition (absorptiometry); and abdominal fat partitioning (magnetic resonance imaging).

Results:

EE-CA and PioFluMet attenuated the androgen excess comparably but had divergent effects on fasting insulinemia; on circulating cholesterol, triglycerides, C-reactive protein, high molecular-weight adiponectin, leptin, and follistatin; on carotid intima-media thickness; on lean mass; and on abdominal, visceral, and hepatic fat, with all these divergences pointing to a healthier condition on low-dose PioFluMet.

Conclusion:

Low-dose PioFluMet compared favorably to EE-CA in adolescents with androgen excess and without pregnancy risk. The efficacy and safety of low-dose PioFluMet remain to be studied over a longer term and in larger cohorts.
Pallial origin of basal forebrain cholinergic neurons in the nucleus basalis of Meynert and horizontal limb of the diagonal band nucleus
Authors: Pombero Ana , Bueno Carlos , Saglietti Laura , Rodenas Monica , Guimera Jordi , Bulfone Alexandro , Martinez Salvador
Published: August 2011

The majority of the cortical cholinergic innervation implicated in attention and memory originates in the nucleus basalis of Meynert and in the horizontal limb of the diagonal band nucleus of the basal prosencephalon. Functional alterations in this system give rise to neuropsychiatric disorders as well as to the cognitive alterations described in Parkinson and Alzheimer's diseases. Despite the functional importance of these basal forebrain cholinergic neurons very little is known about their origin and development. Previous studies suggest that they originate in the medial ganglionic eminence of the telencephalic subpallium; however, our results identified Tbr1-expressing, reelin-positive neurons migrating from the ventral pallium to the subpallium that differentiate into cholinergic neurons in the basal forebrain nuclei projecting to the cortex. Experiments with Tbr1 knockout mice, which lack ventropallial structures, confirmed the pallial origin of cholinergic neurons in Meynert and horizontal diagonal band nuclei. Also, we demonstrate that Fgf8 signaling in the telencephalic midline attracts these neurons from the pallium to follow a tangential migratory route towards the basal forebrain.
Mammary tumorigenesis induced by fibroblast growth factor receptor 1 requires activation of the epidermal growth factor receptor
Authors: Bade Lindsey K. , Goldberg Jodi E. , DeHut Hazel A. , Hall Majken K. , Schwertfeger Kathryn L.
Published: August 2011

Fibroblast growth factor receptor 1 (FGFR1) is an oncoprotein with known involvement in mammary tumorigenesis. To understand how FGFR1 signaling promotes mammary tumorigenesis, an inducible FGFR1 (iFGFR1) system was created previously. Previous studies have demonstrated that upon iFGFR1 activation in vivo, the epidermal growth factor (EGF) ligands amphiregulin (AREG) and epiregulin (EREG) are upregulated. Both AREG and EREG interact with the EGF receptor (EGFR). Here, we investigated whether the FGFR1-induced increase in AREG and EREG expression might coordinately increase EGFR signaling to promote mammary tumorigenesis. Treatment of mouse mammary epithelial cells with either AREG or EREG conferred a greater migratory potential, increased cellular proliferation and increased extracellular regulated kinase 1/2 (ERK1/2) activation. These effects could be blocked with the EGFR-specific inhibitor erlotinib, suggesting that they are EGFR-dependent. In transgenic mice with iFGFR1 under the control of the mouse mammary tumor virus (MMTV) promoter, iFGFR1 activation also led to increased mammary epithelial cell proliferation that was inhibited with erlotinib. Taken together, these data suggest that AREG and EREG mediate tumorigenic phenotypes by activating EGFR signaling, and that the oncogenic potential of FGFR1 requires EGFR activation to promote mammary tumorigenesis.
Strategies of professional phagocytes in vivo: unlike macrophages, neutrophils engulf only surface-associated microbes
Authors: Colucci-Guyon Emma , Tinevez Jean-Yves , Renshaw Stephen A. , Herbomel Philippe
Published: August 2011

The early control of potentially invading microbes by our immune system primarily depends on its main professional phagocytes – macrophages and neutrophils. Although the different functions of these two cell types have been extensively studied, little is known about their respective contributions to the initial control of invading microorganisms before the onset of adaptive immune responses. The naturally translucent zebrafish larva has recently emerged as a powerful model vertebrate in which to visualise the dynamic interactions between leukocytes and microbes in vivo. Using high-resolution live imaging, we found that whereas macrophages efficiently engulf bacteria from blood or fluid-filled body cavities, neutrophils barely do so. By contrast, neutrophils very efficiently sweep up surface-associated, but not fluid-borne, bacteria. Thus the physical presentation of unopsonised microbes is a crucial determinant of neutrophil phagocytic ability. Neutrophils engulf microbes only as they move over them, in a ‘vacuum-cleaner’ type of behaviour. This context-dependent nature of phagocytosis by neutrophils should be of particular relevance to human infectious diseases, especially for the early phase of encounter with microbes new to the host.