bluuebunny/crossref_metadata_2025 huggingface dataset:
Poststroke Conscious Visual Deficit
Authors: Raposo Nicolas , Cauquil Alexandra Séverac , Albucher Jean François , Acket Blandine , Celebrini Simona , Pariente Jérémie , Cognard Christophe , Loubinoux Isabelle , Chollet François
Published: June 2011

Background and Purpose. Little is known about the outcome and recovery mechanisms of visual perception after a focal lesion of the occipital lobe in humans, especially after stroke. In this study, the authors aimed to describe the clinical course and the neural substrates of conscious perceptive visual deficit after posterior cerebral artery infarct. Methods. The authors prospectively included 8 patients (7 men and 1 woman; mean age, 64.6 ± 18 years) with visual deficit induced by partial damage of the striate cortex related to acute posterior cerebral artery infarct. Conscious perception of color and motion was assessed from the acute phase to the third month. Functional magnetic resonance imaging was performed to investigate neural substrates of visual recovery. Results. In the acute phase of stroke, visual deficiency was global (3/8 patients), selective to color (4/8 patients), or selective to motion (1/8 patients). During the follow-up, visual performance increased with respect to color (from 29% to 70%; P < .005) and with respect to motion (from 47% to 74%; P < .005). Despite a lack of ipsilesional V1 area activation in the acute phase, activations in this area and in the contralesional extrastriate cortex were obtained during follow-up. Both ipsilesional and contralesional V4 activations were correlated with better outcome. Conclusions. Extensive visual recovery occurs early after partial acute posterior cerebral artery infarct. Spared islands in ipsilesional V1 area and transcallosal pathways might be involved in poststroke visual recovery.
Gendered Fear of Crime Socialization
Authors: Rader Nicole E. , Haynes Stacy H.
Published: June 2011

This article examines constructs of a theoretical model that explains the social learning process responsible for individuals’ fear of crime levels and how this socialization process differs for men and women. Specifically, the authors apply the original principles of Akers’s social learning theory (i.e., differential association, definitions, differential reinforcement, and imitation) to the gendered fear of crime socialization process. The authors argue that fear of crime socialization and gender socialization become a fused concept called “gendered fear of crime socialization” that leads individuals to establish associations, definitions, reinforcement, and imitation of gendered fear of crime.
Pilates: What Is It? Should It Be Used in Rehabilitation?
Authors: Di Lorenzo Christine E.
Published: June 2011

Context: The interest and popularity of Pilates is increasing worldwide. In addition to being used in fitness programs, it is being used in some rehabilitation programs.

Evidence Acquisition: This review summarizes level III evidence from 1995 to 2009 obtained from PubMed (MEDLINE), CINAHL, and the Internet. Meta-analyses, systematic reviews, randomized controlled trials, and controlled trials published in peer-reviewed journals were retrieved for appraisal. The keywords searched were Pilates and core stabilization.

Results: Ninety articles were identified in MEDLINE and CINAHL; 9 articles satisfied the inclusion criteria for level III evidence.

Conclusion: There is a scientific basis for the effectiveness of Pilates exercise, with limited evidence to support it as a rehabilitative intervention.
Humeral Retrotorsion in Collegiate Baseball Pitchers With Throwing-Related Upper Extremity Injury History
Authors: Myers Joseph B. , Oyama Sakiko , Rucinski Terri Jo , Creighton R. Alexander
Published: June 2011

Background: Collegiate baseball pitchers, as well as position players, exhibit increased humeral retrotorsion compared with individuals with no history of overhead sport participation. Whether the humeral retrotorsion plays a role in the development of throwing-related injuries that are prevalent in collegiate baseball pitchers is unknown.

Hypotheses: Humeral retrotorsion will be significantly different in collegiate pitchers with throwing-related shoulder or elbow injury history compared with pitchers with no injury history. Humeral retrotorsion can also discriminate participants with and without shoulder or elbow injury.

Study Design: Cross-sectional study.

Methods: Comparisons of ultrasonographically-obtained humeral retrotorsion were made between 40 collegiate pitchers with and without history of throwing-related shoulder or elbow injury. The ability of humeral retrotorsion to discriminate injury history was determined from the receiver operating characteristic area under the curve.

Results: Participants with an elbow injury history demonstrated a greater humeral retrotorsion limb difference (mean difference = 7.2°, P = 0.027) than participants with no history of upper extremity injury. Participants with shoulder injury history showed no differences in humeral torsion compared with participants with no history of injury. Humeral retrotorsion limb difference exhibited a fair ability (receiver operating characteristic area under the curve = 0.74) to discriminate elbow injury history.

Conclusions: Collegiate pitchers with a history of elbow injury exhibited a greater limb difference in humeral retrotorsion compared with pitchers with no history of injury. No differences in humeral retrotorsion variables were present in participants with and without shoulder injury history.

Clinical Relevance: Baseball players with a history of elbow injury demonstrated increased humeral retrotorsion, suggesting that the amount of retrotorsion and the development of elbow injury may be associated.
The Notch1-Dll4 signaling pathway regulates mouse postnatal lymphatic development
Authors: Niessen Kyle , Zhang Gu , Ridgway John Brady , Chen Hao , Kolumam Ganesh , Siebel Christian W. , Yan Minhong
Published: June 2011

The Notch signaling pathway plays a fundamental role during blood vessel development. Notch signaling regulates blood vessel morphogenesis by promoting arterial endothelial differentiation and pro-viding spatial and temporal control over “tip cell” phenotype during angiogenic sprouting. Components of the Notch signaling pathway have emerged as potential regulators of lymphatic development, joining the increasing examples of blood vessel regulators that are also involved in lymphatic development. However, in mammals a role for the Notch signaling pathway during lymphatic development remains to be demonstrated. In this report, we show that blockade of Notch1 and Dll4, with specific function-blocking antibodies, results in defective postnatal lymphatic development in mice. Mechanistically, Notch1-Dll4 blockade is associated with down-regulation of EphrinB2 expression, been shown to be critically involved in VEGFR3/VEGFC signaling, resulting in reduced lymphangiogenic sprouting. In addition, Notch1-Dll4 blockade leads to compromised expression of distinct lymphatic markers and to dilation of collecting lymphatic vessels with reduced and disorganized mural cell coverage. Finally, Dll4-blockade impairs wound closure and severely affects lymphangiogenesis during the wound healing in adult mouse skin. Thus, our study demonstrates for the first time in a mammalian system that Notch1-Dll4 signaling pathway regulates postnatal lymphatic development and pathologic lymphangiogenesis.
Monocytic microparticles activate endothelial cells in an IL-1β–dependent manner
Authors: Wang Jian-Guo , Williams Julie C. , Davis Beckley K. , Jacobson Ken , Doerschuk Claire M. , Ting Jenny P.-Y. , Mackman Nigel
Published: June 2011

Microparticles (MPs) are shed from activated and dying cells. They can transmit signals from cell to cell, locally or at a distance through the circulation. Monocytic MPs are elevated in different diseases, including bacterial infections. Here, we investigated how monocytic MPs activate endothelial cells. We found that MPs from lipopolysaccharide (LPS)–treated THP-1 monocytic cells bind to and are internalized by human endothelial cells. MPs from LPS-treated THP-1 cells, but not untreated cells, induced phosphorylation of ERK1/2, activation of the nuclear factor-κB pathway and expression of cell adhesion molecules intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin. Similar results were observed using MPs from LPS-treated peripheral blood mononuclear cells. We next investigated the mechanism by which monocytic MPs activated endothelial cells and found that they contain IL-1β and components of the inflammasome, including apoptosis-associated speck-like protein containing a CARD, caspase-1, and NLRP3. Importantly, knockdown of NLRP3 in THP-1 cells reduced the activity of the MPs and blockade of the IL-1 receptor on endothelial cells decreased MP-dependent induction of cell adhesion molecules. Therefore, monocytic MPs contain IL-1β and may amplify inflammation by enhancing the activation of the endothelium.
A pilot study of subcutaneous decitabine in β-thalassemia intermedia
Authors: Olivieri Nancy F. , Saunthararajah Yogen , Thayalasuthan Vivek , Kwiatkowski Janet , Ware Russell E. , Kuypers Frans A. , Kim Hae-Young , Trachtenberg Felicia L. , Vichinsky Elliott P. ,   for the Thalassemia Clinical Research Network
Published: June 2011

Ineffective erythropoiesis, the hallmark of β-thalassemia, is a result of α/non-α globin chain imbalance.1 One strategy to redress globin-chain imbalance is to induce γ-globin gene (HBG) expression. Repression of HBG in adult erythroid cells involves DNA methylation and other epigenetic changes. Therefore, the cytosine analog decitabine, which can deplete DNA methyltransferase 1 (DNMT1), can potentially activate HBG. In 5 patients with β-thalassemia intermedia, a dose and schedule of decitabine intended to deplete DNMT1 without causing significant cytotoxicity (0.2 mg/kg subcutaneous 2 times per week for 12 weeks) increased total hemoglobin from 7.88 ± 0.88 g/dL to 9.04 ± 0.77 g/dL (P = .004) and absolute fetal hemoglobin from 3.64 ± 1.13 g/dL to 4.29 ± 1.13 g/dL (P = .003). Significant favorable changes also occurred in indices of hemolysis and red blood cell densitometry. Consistent with a noncytotoxic, differentiation altering mechanism of action, the major side effect was an asymptomatic increase in platelet counts without erythrocyte micronucleus or VDJ recombination assay evidence of genotoxicity. This study was registered at www.clinicaltrials.gov as #NCT00661726.
Metalloproteinases in idiopathic pulmonary fibrosis
Authors: Dancer R.C.A. , Wood A.M. , Thickett D.R.
Published: June 2011

In this article, we outline the current state of knowledge about the balance between collagen production and degradation in idiopathic pulmonary fibrosis (IPF). The dysregulated action of metalloproteinases implicated in IPF may play a central role in IPF pathogenesis. Inhibiting metalloproteinases in IPF may, therefore, have therapeutic potential, but our knowledge of their pathophysiological role is held back by limited animal models and the lack of specific inhibitors.
Exhaled air molecular profiling in relation to inflammatory subtype and activity in COPD
Authors: Fens N. , de Nijs S.B. , Peters S. , Dekker T. , Knobel H.H. , Vink T.J. , Willard N.P. , Zwinderman A.H. , Krouwels F.H. , Janssen H-G. , Lutter R. , Sterk P.J.
Published: June 2011

Eosinophilic inflammation in chronic obstructive pulmonary disease (COPD) is predictive for responses to inhaled steroids. We hypothesised that the inflammatory subtype in mild and moderate COPD can be assessed by exhaled breath metabolomics.

Exhaled compounds were analysed using gas chromatography and mass spectrometry (GC-MS) and electronic nose (eNose) in 28 COPD patients (12/16 Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I/II, respectively). Differential cell counts, eosinophil cationic protein (ECP) and myeloperoxidase (MPO) were measured in induced sputum. Relationships between exhaled compounds, eNose breathprints and sputum inflammatory markers were analysed and receiver operating characteristic (ROC) curves were constructed.

Exhaled compounds were highly associated with sputum cell counts (eight compounds with eosinophils, 17 with neutrophils; p<0.01). Only one compound (alkylated benzene) overlapped between eosinophilic and neutrophilic profiles. GC-MS and eNose breathprints were associated with markers of inflammatory activity in GOLD stage I (ECP: 19 compounds, p<0.01; eNose breathprint r=0.84, p=0.002) (MPO: four compounds, p<0.01; eNose r=0.72, p=0.008). ROC analysis for eNose showed high sensitivity and specificity for inflammatory activity in mild COPD (ECP: area under the curve (AUC) 1.00; MPO: AUC 0.96) but not for moderate COPD.

Exhaled molecular profiles are closely associated with the type of inflammatory cell and their activation status in mild and moderate COPD. This suggests that breath analysis may be used for assessment and monitoring of airway inflammation in COPD.
Parent misperception of control in childhood/adolescent asthma: the Room to Breathe survey
Authors: Carroll W.D. , Wildhaber J. , Brand P.L.P.
Published: June 2011

The aim of our study was to determine how often asthma control is achieved in children and adolescents, and how asthma affects parents' and children's daily lives.

Interviews, including the childhood asthma control test (C-ACT), were conducted with 1,284 parents of asthmatic children (aged 4–15 yrs), as well as with the children themselves (aged 8–15 yrs; n=943), in Canada, Greece, Hungary, the Netherlands, South Africa and the UK.

Parents reported mild asthma attacks at least weekly in 11% of children, and serious attacks (requiring oral corticosteroids or hospitalisation) at least annually in 35%. Although 73% of parents described their child's asthma as mild or intermittent, 40% of children/adolescents had C-ACT scores ≤19, indicating inadequate control, and only 14.7% achieved complete Global Initiative for Asthma (GINA)-defined control and just 9.2% achieved Scottish Intercollegiate Guidelines Network (SIGN)/British Thoracic Society (BTS)-defined control. Guideline-defined asthma control was significantly less common than well-controlled asthma using the C-ACT (p<0.001). Asthma restricted the child's activities in 39% of families and caused lifestyle changes in 70%.

Complete asthma control is uncommon in children worldwide. Guideline-defined control measures appear to be more stringent than those defined by C-ACT or families. Overall, parents underestimate their child's asthma severity and overestimate asthma control. This is a major potential barrier to successful asthma treatment in children.
Analysis of the acute phase responses of Serum Amyloid A, Haptoglobin and Type 1 Interferon in cattle experimentally infected with foot-and-mouth disease virus serotype O
Authors: Stenfeldt Carolina , Heegaard Peter MH , Stockmarr Anders , Tjørnehøj Kirsten , Belsham Graham J
Published: June 2011

A series of challenge experiments were performed in order to investigate the acute phase responses to foot-and-mouth disease virus (FMDV) infection in cattle and possible implications for the development of persistently infected "carriers". The host response to infection was investigated through measurements of the concentrations of the acute phase proteins (APPs) serum amyloid A (SAA) and haptoglobin (HP), as well as the bioactivity of type 1 interferon (IFN) in serum of infected animals. Results were based on measurements from a total of 36 infected animals of which 24 were kept for observational periods exceeding 28 days in order to determine the carrier-status of individual animals. The systemic host response to FMDV in infected animals was evaluated in comparison to similar measurements in sera from 6 mock-inoculated control animals.

There was a significant increase in serum concentrations of both APPs and type 1 IFN in infected animals coinciding with the onset of viremia and clinical disease. The measured parameters declined to baseline levels within 21 days after inoculation, indicating that there was no systemically measurable inflammatory reaction related to the carrier state of FMD. There was a statistically significant difference in the HP response between carriers and non-carriers with a lower response in the animals that subsequently developed into FMDV carriers. It was concluded that the induction of SAA, HP and type 1 IFN in serum can be used as markers of acute infection by FMDV in cattle.
Digging deeper into lymphatic vessel formation in vitro and in vivo
Authors: Detry Benoit , Bruyère Françoise , Erpicum Charlotte , Paupert Jenny , Lamaye Françoise , Maillard Catherine , Lenoir Bénédicte , Foidart Jean-Michel , Thiry Marc , Noël Agnès
Published: June 2011

Background

Abnormal lymphatic vessel formation (lymphangiogenesis) is associated with different pathologies such as cancer, lymphedema, psoriasis and graft rejection. Lymphatic vasculature displays distinctive features than blood vasculature, and mechanisms underlying the formation of new lymphatic vessels during physiological and pathological processes are still poorly documented. Most studies on lymphatic vessel formation are focused on organism development rather than lymphangiogenic events occurring in adults. We have here studied lymphatic vessel formation in twoin vivomodels of pathological lymphangiogenesis (corneal assay and lymphangioma). These data have been confronted to those generated in the recently set upin vitromodel of lymphatic ring assay. Ultrastructural analyses through Transmission Electron Microscopy (TEM) were performed to investigate tube morphogenesis, an important differentiating process observed during endothelial cell organization into capillary structures.

Results

In bothin vivomodels (lymphangiogenic corneal assay and lymphangioma), migrating lymphatic endothelial cells extended long processes exploring the neighboring environment and organized into cord-like structures. Signs of intense extracellular matrix remodeling were observed extracellularly and inside cytoplasmic vacuoles. The formation of intercellular spaces between endothelial cells led to tube formation. Proliferating lymphatic endothelial cells were detected both at the tips of sprouting capillaries and inside extending sprouts. The different steps of lymphangiogenesis observedin vivoare fully recapitulatedin vitro, in the lymphatic ring assay and include: (1) endothelial cell alignment in cord like structure, (2) intracellular vacuole formation and (3) matrix degradation.

Conclusions

In this study, we are providing evidence for lymphatic vessel formation through tunneling relying on extensive matrix remodeling, migration and alignment of sprouting endothelial cells into tubular structures. In addition, our data emphasize the suitability of the lymphatic ring assay to unravel mechanisms underlying lymphangiogenesis.
Role of the SaeRS two-component regulatory system in Staphylococcus epidermidisautolysis and biofilm formation
Authors: Lou Qiang , Zhu Tao , Hu Jian , Ben Haijing , Yang Jinsong , Yu Fangyou , Liu Jingran , Wu Yang , Fischer Adrien , Francois Patrice , Schrenzel Jacques , Qu Di
Published: June 2011

Background

Staphylococcus epidermidis(SE) has emerged as one of the most important causes of nosocomial infections. The SaeRS two-component signal transduction system (TCS) influences virulence and biofilm formation inStaphylococcus aureus. The deletion ofsaeRinS. epidermidisresults in impaired anaerobic growth and decreased nitrate utilization. However, the regulatory function of SaeRS on biofilm formation and autolysis inS. epidermidisremains unclear.

Results

ThesaeRSgenes of SE1457 were deleted by homologous recombination. ThesaeRSdeletion mutant, SE1457ΔsaeRS, exhibited increased biofilm formation that was disturbed more severely (a 4-fold reduction) by DNase I treatment compared to SE1457 and the complementation strain SE1457saec. Compared to SE1457 and SE1457saec, SE1457ΔsaeRSshowed increased Triton X-100-induced autolysis (approximately 3-fold) and decreased cell viability in planktonic/biofilm states; further, SE1457ΔsaeRSalso released more extracellular DNA (eDNA) in the biofilms. Correlated with the increased autolysis phenotype, the transcription of autolysis-related genes, such asatlEandaae, was increased in SE1457ΔsaeRS. Whereas the expression of accumulation-associated protein was up-regulated by 1.8-fold in 1457ΔsaeRS, the expression of an N-acetylglucosaminyl transferase enzyme (encoded byicaA) critical for polysaccharide intercellular adhesin (PIA) synthesis was not affected by the deletion ofsaeRS.

Conclusions

Deletion ofsaeRSinS. epidermidisresulted in an increase in biofilm-forming ability, which was associated with increased eDNA release and up-regulated Aap expression. The increased eDNA release from SE1457ΔsaeRSwas associated with increased bacterial autolysis and decreased bacterial cell viability in the planktonic/biofilm states.
Comparative diffusion assay to assess efficacy of topical antimicrobial agents against Pseudomonas aeruginosa in burns care
Authors: Aujoulat Fabien , Lebreton Françoise , Romano Sara , Delage Milena , Marchandin Hélène , Brabet Monique , Bricard Françoise , Godreuil Sylvain , Parer Sylvie , Jumas-Bilak Estelle
Published: June 2011

Background

Severely burned patients may develop life-threatening nosocomial infections due to Pseudomonas aeruginosa, which can exhibit a high-level of resistance to antimicrobial drugs and has a propensity to cause nosocomial outbreaks. Antiseptic and topical antimicrobial compounds constitute major resources for burns care but in vitro testing of their activity is not performed in practice.

Results

In our burn unit, a P. aeruginosa clone multiresistant to antibiotics colonized or infected 26 patients over a 2-year period. This resident clone was characterized by PCR based on ERIC sequences. We investigated the susceptibility of the resident clone to silver sulphadiazine and to the main topical antimicrobial agents currently used in the burn unit. We proposed an optimized diffusion assay used for comparative analysis of P. aeruginosa strains. The resident clone displayed lower susceptibility to silver sulphadiazine and cerium silver sulphadiazine than strains unrelated to the resident clone in the unit or unrelated to the burn unit.

Conclusions

The diffusion assay developed herein detects differences in behaviour against antimicrobials between tested strains and a reference population. The method could be proposed for use in semi-routine practice of medical microbiology.
Stimulation of neoplastic mouse lung cell proliferation by alveolar macrophage-derived, insulin-like growth factor-1 can be blocked by inhibiting MEK and PI3K activation
Authors: Fritz Jason M , Dwyer-Nield Lori D , Malkinson Alvin M
Published: June 2011

Background

Worldwide, lung cancer kills more people than breast, colon and prostate cancer combined. Alterations in macrophage number and function during lung tumorigenesis suggest that these immune effector cells stimulate lung cancer growth. Evidence from cancer models in other tissues suggests that cancer cells actively recruit growth factor-producing macrophages through a reciprocal signaling pathway. While the levels of lung macrophages increase during tumor progression in mouse models of lung cancer, and high pulmonary macrophage content correlates with a poor prognosis in human non-small cell lung cancer, the specific role of alveolar macrophages in lung tumorigenesis is not clear.

Methods

After culturing either an immortalized lung macrophage cell line or primary murine alveolar macrophages from naïve and lung-tumor bearing mice with primary tumor isolates and immortalized cell lines, the effects on epithelial proliferation and cellular kinase activation were determined. Insulin-like growth factor-1 (IGF-1) was quantified by ELISA, and macrophage conditioned media IGF-1 levels manipulated by IL-4 treatment, immuno-depletion and siRNA transfection.

Results

Primary macrophages from both naïve and lung-tumor bearing mice stimulated epithelial cell proliferation. The lungs of tumor-bearing mice contained 3.5-times more IGF-1 than naïve littermates, and media conditioned by freshly isolated tumor-educated macrophages contained more IGF-1 than media conditioned by naïve macrophages; IL-4 stimulated IGF-1 production by both macrophage subsets. The ability of macrophage conditioned media to stimulate neoplastic proliferation correlated with media IGF-1 levels, and recombinant IGF-1 alone was sufficient to induce epithelial proliferation in all cell lines evaluated. Macrophage-conditioned media and IGF-1 stimulated lung tumor cell growth in an additive manner, while EGF had no effect. Macrophage-derived factors increased p-Erk1/2, p-Akt and cyclin D1 levels in neoplastic cells, and the combined inhibition of both MEK and PI3K ablated macrophage-mediated increases in epithelial growth.

Conclusions

Macrophages produce IGF-1 which directly stimulates neoplastic proliferation through Erk and Akt activation. This observation suggests that combining macrophage ablation therapy with IGF-1R, MEK and/or PI3K inhibition could improve therapeutic response in human lung cancer. Exploring macrophage-based intervention could be a fruitful avenue for future research.
Rare human papillomavirus 16 E6 variants reveal significant oncogenic potential
Authors: Zehbe Ingeborg , Lichtig Hava , Westerback Ashley , Lambert Paul F , Tommasino Massimo , Sherman Levana
Published: June 2011

The aim of this study was to determine whether low prevalence human papillomavirus (HPV) 16 E6 variants differ from high prevalence types in their functional abilities. We evaluated functions relevant to carcinogenesis for the rarely-detected European variants R8Q, R10G and R48W as compared to the commonly detected L83V. Human immortalized keratinocytes (NIKS) stably transduced with the E6 variants were used in most functional assays. Low and high prevalence E6 variants displayed similar abilities in abrogation of growth arrest and inhibition of p53 elevation induced by actinomycin D. Differences were detected in the abilities to dysregulate stratification and differentiation of NIKS in organotypic raft cultures, modulate detachment induced apoptosis (anoikis) and hyperactivate Wnt signaling. No distinctive phenotype could be assigned to include all rare variants. Like L83V, raft cultures derived from variants R10G and R48W similarly induced hyperplasia and aberrantly expressed keratin 5 in the suprabasal compartment with significantly lower expression of keratin 10. Unlike L83V, both variants, and particularly R48W, induced increased levels of anoikis upon suspension in semisolid medium. R8Q induced a unique phenotype characterized by thin organotypic raft cultures, low expression of keratin 10, and high expression of keratins 5 and 14 throughout all raft layers. Interestingly, in a reporter based assay R8Q exhibited a higher ability to augment TCF/β-catenin transcription. The data suggests that differences in E6 variant prevalence in cervical carcinoma may not be related to the carcinogenic potential of the E6 protein.
In utero protein restriction causes growth delay and alters sperm parameters in adult male rats
Authors: Toledo Fabíola C , Perobelli Juliana E , Pedrosa Flávia PC , Anselmo-Franci Janete A , Kempinas Wilma DG
Published: June 2011

Background

Recent studies have supported the concept of "fetal programming" which suggests that during the intrauterine development the fetus may be programmed to develop diseases in adulthood. The possible effects of in utero protein restriction on sexual development of rat male offspring were evaluated in the present study.

Methods

Pregnant Wistar rats were divided into two experimental groups: one group treated with standard chow (SC, n = 8, 17% protein) and the other group treated with hypoproteic chow (HC, n = 10, 6% protein) throughout gestation. After gestation the two experimental groups received standard chow. To evaluate the possible late reproductive effects of in utero protein restriction, the male offspring of both groups were assessed at different phases of sexual development: prepubertal (30 days old); peripubertal (60 days old); adult (90 days old). Student's t-test and Mann-Whitney test were utilized. Differences were considered significant when p < 0.05.

Results

We found that in utero protein restriction reduced the body weight of male pups on the first postnatal day and during the different sexual development phases (prepubertal, peripubertal and adult). During adulthood, Sertoli cell number, sperm motility and sperm counts in the testis and epididymal cauda were also reduced in HC. Furthermore, the numbers of sperm presenting morphological abnormalities and cytoplasmic drop retention were higher in HC.

Conclusions

In conclusion, in utero protein restriction, under these experimental conditions, causes growth delay and alters male reproductive-system programming in rats, suggesting impairment of sperm quality in adulthood.
Human resources for maternal, newborn and child health: from measurement and planning to performance for improved health outcomes
Authors: Gupta Neeru , Maliqi Blerta , França Adson , Nyonator Frank , Pate Muhammad A , Sanders David , Belhadj Hedia , Daelmans Bernadette
Published: June 2011

Background

There is increasing attention, globally and in countries, to monitoring and addressing the health systems and human resources inputs, processes and outputs that impede or facilitate progress towards achieving the Millennium Development Goals for maternal and child health. We reviewed the situation of human resources for health (HRH) in 68 low- and middle-income countries that together account for over 95% of all maternal and child deaths.

Methods

We collected and analysed cross-nationally comparable data on HRH availability, distribution, roles and functions from new and existing sources, and information from country reviews of HRH interventions that are associated with positive impacts on health services delivery and population health outcomes.

Results

Findings from 68 countries demonstrate availability of doctors, nurses and midwives is positively correlated with coverage of skilled birth attendance. Most (78%) of the target countries face acute shortages of highly skilled health personnel, and large variations persist within and across countries in workforce distribution, skills mix and skills utilization. Too few countries appropriately plan for, authorize and support nurses, midwives and community health workers to deliver essential maternal, newborn and child health-care interventions that could save lives.

Conclusions

Despite certain limitations of the data and findings, we identify some key areas where governments, international partners and other stakeholders can target efforts to ensure a sufficient, equitably distributed and efficiently utilized health workforce to achieve MDGs 4 and 5.
Strong convergence theorems by hybrid projection methods for equilibrium problems and fixed point problems of the asymptotically quasi-ϕ-nonexpansive mappings
Authors: Kim Jong Kyu
Published: June 2011

We consider a hybrid projection method for finding a common element in the fixed point set of an asymptotically quasi-ϕ-nonexpansive mapping and in the solution set of an equilibrium problem. Strong convergence theorems of common elements are established in a uniformly smooth and strictly convex Banach space which has the Kadec-Klee property.

2000 Mathematics subject classification: 47H05, 47H09, 47H10, 47J25
Prevention of the β-amyloid peptide-induced inflammatory process by inhibition of double-stranded RNA-dependent protein kinase in primary murine mixed co-cultures
Authors: Couturier J , Paccalin M , Morel M , Terro F , Milin S , Pontcharraud R , Fauconneau B , Page G
Published: June 2011

Background

Inflammation may be involved in the pathogenesis of Alzheimer's disease (AD). There has been little success with anti-inflammatory drugs in AD, while the promise of anti-inflammatory treatment is more evident in experimental models. A new anti-inflammatory strategy requires a better understanding of molecular mechanisms. Among the plethora of signaling pathways activated by β-amyloid (Aβ) peptides, the nuclear factor-kappa B (NF-κB) pathway could be an interesting target. In virus-infected cells, double-stranded RNA-dependent protein kinase (PKR) controls the NF-κB signaling pathway. It is well-known that PKR is activated in AD. This led us to study the effect of a specific inhibitor of PKR on the Aβ42-induced inflammatory response in primary mixed murine co-cultures, allowing interactions between neurons, astrocytes and microglia.

Methods

Primary mixed murine co-cultures were prepared in three steps: a primary culture of astrocytes and microglia for 14 days, then a primary culture of neurons and astrocytes which were cultured with microglia purified from the first culture. Before exposure to Aβ neurotoxicity (72 h), co-cultures were treated with compound C16, a specific inhibitor of PKR. Levels of tumor necrosis factor-α (TNFα), interleukin (IL)-1β, and IL-6 were assessed by ELISA. Levels of PT451-PKR and activation of IκB, NF-κB and caspase-3 were assessed by western blotting. Apoptosis was also followed using annexin V-FITC immunostaining kit. Subcellular distribution of PT451-PKR was assessed by confocal immunofluorescence and morphological structure of cells by scanning electron microscopy. Data were analysed using one-way ANOVA followed by a Newman-Keuls' post hoc test

Results

In these co-cultures, PKR inhibition prevented Aβ42-induced activation of IκB and NF-κB, strongly decreased production and release of tumor necrosis factor (TNFα) and interleukin (IL)-1β, and limited apoptosis.

Conclusion

In spite of the complexity of the innate immune response, PKR inhibition could be an interesting anti-inflammatory strategy in AD.
Lymph node-derived donor encephalitogenic CD4+T cells in C57BL/6 mice adoptive transfer experimental autoimmune encephalomyelitis highly express GM-CSF and T-bet
Authors: Cravens Petra D , Hussain Rehana Z , Zacharias Tresa E , Ben Li-Hong , Herndon Emily , Vinnakota Ramya , Lambracht-Washington Doris , Nessler Stefan , Zamvil Scott S , Eagar Todd N , Stüve Olaf
Published: June 2011

Experimental autoimmune encephalomyelitis (EAE) is a relevant animal model for the human demyelinating inflammatory disorder of the central nervous system (CNS), multiple sclerosis (MS). Induction of EAE by adoptive transfer allows studying the role of the donor T lymphocyte in disease pathogenesis. It has been challenging to reliably induce adoptive transfer EAE in C57BL/6 (H-2b) mice. The goal of this study was to develop a reproducible and high yield protocol for adoptive transfer EAE in C57BL/6 mice. A step-wise experimental approach permitted us to develop a protocol that resulted in a consistent relatively high disease incidence of ~70% in recipient mice. Donor mice were immunized with myelin oligodendrocyte glycoprotein (MOG)p35-55in complete Freund's adjuvant (CFA) followed by pertussis toxin (PT). Only lymph node cells (LNC) isolated at day 12 post immunization, and restimulatedin vitrofor 72 hours with 10 μg/mL of MOGp35-55and 0.5 ng/mL of interleukin-12 (IL-12) were able to transfer disease. The ability of LNC to transfer disease was associated with the presence of inflammatory infiltrates in the CNS at day 12. Interferon gamma (IFNγ) was produced at comparable levels in cell cultures prepared from mice at both day 6 and day 12 post immunization. By contrast, there was a trend towards a negative association between IL-17 and disease susceptibility in our EAE model. The amount of GM-CSF secreted was significantly increased in the culture supernatants from cells collected at day 12 post immunization versus those collected at day 6 post-immunization. Activated CD4+T cells present in the day 12 LNC cultures maintained expression of the transcription factor T-bet, which has been shown to regulate the expression of the IL-23 receptor. Also, there was an increased prevalence of MOGp35-55-specific CD4+T cells in day 12 LNC afterin vitrore-stimulation. In summary, encephalitogenic LNC that adoptively transfer EAE in C57BL/6 mice were not characterized by a single biomarker in our study, but by a composite of inflammatory markers. Our data further suggest that GM-CSF expression by CD4+T cells regulated by IL-23 contributes to their encephalitogenicity in our EAE model.
Glutamate Acts as a Neurotransmitter for Gastrin Releasing Peptide-Sensitive and Insensitive Itch-Related Synaptic Transmission in Mammalian Spinal Cord
Authors: Koga Kohei , Chen Tao , Li Xiang-Yao , Descalzi Giannina , Ling Jennifer , Gu Jianguo , Zhuo Min
Published: June 2011

Itch sensation is one of the major sensory experiences of human and animals. Recent studies have proposed that gastrin releasing peptide (GRP) is a key neurotransmitter for itch in spinal cord. However, no direct evidence is available to indicate that GRP actually mediate responses between primary afferent fibers and dorsal horn neurons. Here we performed integrative neurobiological experiments to test this question. We found that a small population of rat dorsal horn neurons responded to GRP application with increases in calcium signaling. Whole-cell patch-clamp recordings revealed that a part of superficial dorsal horn neurons responded to GRP application with the increase of action potential firing in adult rats and mice, and these dorsal horn neurons received exclusively primary afferent C-fiber inputs. On the other hands, few Aδ inputs receiving cells were found to be GRP positive. Finally, we found that evoked sensory responses between primary afferent C fibers and GRP positive superficial dorsal horn neurons are mediated by glutamate but not GRP. CNQX, a blocker of AMPA and kainate (KA) receptors, completely inhibited evoked EPSCs, including in those Fos-GFP positive dorsal horn cells activated by itching. Our findings provide the direct evidence that glutamate is the principal excitatory transmitter between C fibers and GRP positive dorsal horn neurons. Our results will help to understand the neuronal mechanism of itch and aid future treatment for patients with pruritic disease.
The increase of methicillin-resistant Staphylococcus aureus(MRSA) and the presence of an unusual sequence type ST49 in slaughter pigs in Switzerland
Authors: Overesch Gudrun , Büttner Sabina , Rossano Alexandra , Perreten Vincent
Published: June 2011

Background

In years past, methicillin-resistant S. aureus (MRSA) has been frequently detected in pigs in Europe, North America and Asia. Recent, yet sporadic studies have revealed a low occurrence of MRSA in Switzerland. In 2009, a monitoring survey of the prevalence and genetic diversity of methicillin-resistant S. aureus (MRSA) in slaughter pigs in Switzerland was conducted using methods recommended by the EU guidelines, and using a sampling strategy evenly distributed throughout the year and representative of the Swiss slaughter pig population. Monitoring should determine if the overall prevalence of MRSA in the entire country is increasing over the years and if specific multi-resistant MRSA clones are spreading over the country.

Results

In 2009, the nasal cavities of eight out of 405 randomly selected pigs were positive for MRSA, representing a prevalence of 2.0% (95% CI 0.9-3.9). The following year, 23 out of 392 pigs were positive for MRSA [5.9% prevalence (95% CI 3.8-8.7)]. Three multilocus sequence types (ST), four spa types and two types of staphylococcal cassette chromosome mec (SCCmec) elements were detected. The most frequent genotypes were ST398 (MLST)-(spa)t034-V(SCCmec) (n = 18) and ST49-t208-V (n = 7), followed by ST398-t011-V (n = 4), ST398-t1451-V (n = 1), and ST1-t2279-IVc (n = 1). The isolates displayed resistance to ß-lactams [mecA, (31/31); blaZ, (19/31)]; tetracycline [tet(M), (31/31); tet(K), (30/31)] (n = 31); macrolides and lincosamides [erm(C) (4/31) or erm(A) (18/31)] (n = 22); tiamulin [vga(A)v (9/31) or unknown mechanism (18/31)] (n = 27); trimethoprim [dfr(G) (18/31); spectinomycin [ant(9)-Ia (19/31) or unknown mechanism (3/31)] (n = 22); streptomycin [str (19/31)]; sulphamethoxazole (7/31) and ciprofloxacin (n = 1) (mechanisms not determined).

Conclusions

This study is the first to describe the presence of MRSA ST49 in slaughter pigs, and to demonstrate a significant and nearly three-fold increase of MRSA prevalence in pigs within two years. The presence of a specific clonal lineage of MRSA from Switzerland suggests that it has been selected in Swiss pig husbandry. Effective hygiene measures should be enhanced within the entire pig production chain to suppress the spread of these pathogens into the community.
Circulating tumor cells as prognostic and predictive markers in metastatic breast cancer patients receiving first-line systemic treatment
Authors: Giuliano Mario , Giordano Antonio , Jackson Summer , Hess Kenneth R , De Giorgi Ugo , Mego Michal , Handy Beverly C , Ueno Naoto T , Alvarez Ricardo H , De Laurentiis Michelino , De Placido Sabino , Valero Vicente , Hortobagyi Gabriel N , Reuben James M , Cristofanilli Massimo
Published: June 2011

Introduction

Circulating tumor cells (CTCs) represent an independent predictor of outcome in patients with metastatic breast cancer (MBC). We assessed the prognostic impact of CTCs according to different first-line systemic treatments, and explored their potential predictive value in MBC patients.

Methods

We retrospectively evaluated 235 newly diagnosed MBC patients, treated at the University of Texas MD Anderson Cancer Center. All patients had a baseline CTC assessment performed with CellSearch®. Progression-free survival and overall survival were compared with the log-rank test between groups, according to CTC count (< 5 vs. ≥ 5) and type of systemic therapy. We further explored the predictive value of baseline CTCs in patients receiving different treatments.

Results

At a median follow-up of 18 months, the CTC count was confirmed to be a robust prognostic marker in the overall population (median progression-free survival 12.0 and 7.0 months for patients with CTC < 5 and ≥ 5, respectively; P < 0.001). Conversely, in patients with human epidermal growth factor receptor-2-overexpressed/amplified tumors receiving trastuzumab or lapatinib, the baseline CTC count was not prognostic (median progression-free survival 14.5 months for patients with CTC < 5 and 16.1 months for those with CTC ≥ 5; P = 0.947). Furthermore, in patients with human epidermal growth factor receptor-2 normal tumors, a baseline CTC count ≥ 5 identified subjects who derived benefit from more aggressive treatments, including combination chemotherapy and chemotherapy plus bevacizumab.

Conclusions

This analysis suggests that the prognostic information provided by CTC count may be useful in patient stratifications and therapeutic selection, particularly in the group with positive CTCs, in which various therapeutic choices may procure differential palliative benefit.
Poetics of the Flesh: An Interview with Kaja Silverman
Authors: Watson Janell
Published: June 2011

Kaja Silverman's body of work spans the disciplines of English, film studies, semiotics, psychoanalytic criticism, feminist theory, masculinity studies, and art history. In this interview, Silverman discusses her career as an interdisciplinarian, beginning with the days when interdisciplinarity was not yet trendy and continuing with her nineteen years in the rhetoric department at the University of California at Berkeley. She describes the evolution of her relationship to Freud's thought, her ongoing commitment to feminism, her more recent engagement with Heidegger, and the place of painting, photography, and poetry in her work. Other figures discussed include John Donne, James Coleman, Gerhard Richter, and Hannah Arendt. The interview culminates with some thoughts on the concepts of flesh and of analogy, the topic of the book she is currently writing.
Double-stranded RNA binding proteins DRB2 and DRB4 have an antagonistic impact on polymerase IV-dependent siRNA levels in Arabidopsis
Authors: Pélissier Thierry , Clavel Marion , Chaparro Cristian , Pouch-Pélissier Marie-Noëlle , Vaucheret Hervé , Deragon Jean-Marc
Published: June 2011

Biogenesis of the vast majority of plant siRNAs depends on the activity of the plant-specific RNA polymerase IV (PolIV) enzyme. As part of the RNA-dependent DNA methylation (RdDM) process, PolIV-dependent siRNAs (p4-siRNAs) are loaded onto an ARGONAUTE4-containing complex and guide de novo DNA methyltransferases to target loci. Here we show that the double-stranded RNA binding proteins DRB2 and DRB4 are required for proper accumulation of p4-siRNAs. In flowers, loss of DRB2 results in increased accumulation of p4-siRNAs but not ta-siRNAs, inverted repeat (IR)-derived siRNAs, or miRNA. Loss of DRB2 does not impair uniparental expression of p4-dependent siRNAs in developing endosperm, indicating that p4-siRNA increased accumulation is not the result of the activation of the polIV pathway in the male gametophyte. In contrast to drb2, drb4 mutants exhibit reduced p4-siRNA levels, but the extent of this reduction is variable, according to the nature and size of the p4-siRNAs. Loss of DRB4 also leads to a spectacular increase of p4-independent IR-derived 24-nt siRNAs, suggesting a reallocation of factors from p4-dependent to p4-independent siRNA pathways in drb4. Opposite effects of drb2 and drb4 mutations on the accumulation of p4-siRNAs were also observed in vegetative tissues. Moreover, transgenic plants overexpressing DRB2 mimicked drb4 mutants at the morphological and molecular levels, confirming the antagonistic roles of DRB2 and DRB4.
Benzopyrrole derivatives as effective anion receptors in highly competitive solvents
Authors: Jurczak Janusz , Chmielewski Michał J. , Dydio Paweł , Lichosyt Dawid , Ulatowski Filip , Zieliński Tomasz
Published: June 2011

Neutral anion receptors working in highly demanding solvents are new materials being sought. Benzopyrroles are more acidic than amides and pyrrole itself, and are promising building blocks in the design of host compounds. A whole series of receptors based upon benzopyrroles were synthesized and evaluated. They include carbazole, dipyrrolonaph-thalene, and 7-aminoindole-based hosts. Most of them demonstrate moderate binding affinities in dimethyl sulfoxide (DMSO) and have good selectivity toward tetrahedral oxyanions. Recently, a group of receptors utilizing 7-aminoindole and urea moieties proved to work in a very competitive solvent—methanol.
The Art in Gastronomy: A Modernist Perspective
Authors: myhrvold nathan
Published: June 2011

In the twentieth century, Modernism swept through virtually every form of art and design—except cuisine. In painting, dance, architecture, literature, and nearly every other form of intellectual creative expression, the continual rejection of the old in favor of new, avant-garde styles became, as Renato Poggioli observed, “the typical chronic condition.” But it was not until the 1970s that Nouvelle Cuisine began to transform classical French cooking, and Nouvelle was a rather limited revolution, narrow in its focus on techniques and ingredients, and limited as well in its impact on Spanish and Italian cuisine.

A true Modernist revolution in food has begun only recently, as chefs such as Ferran Adrià began consciously developing gastronomic experiences that transform meals into dialogues between chef and diner. Avant-garde cooking emphasizes novel, unconventional presentation of familiar flavor themes—the “deconstruction” of the meal by evoking diners’ memories of past meals while taking the dishes in novel directions. A meal at elBulli or other Modernist restaurants often exposes conventions that guests do not even realize exist until the innovative food violates them. Like other good art, Modernist cuisine is challenging and provocative.

Dozens of chefs around the world are now advancing this culinary movement as it follows a trajectory that is similar, in many ways, to the Modernist transformations of other cultural disciplines. Like those predecessor movements, Modernist cuisine has faced some resistance and criticism. But it has arrived.