bluuebunny/crossref_metadata_2025 huggingface dataset:
ThePTPN11loss-of-function mutation Q510E-Shp2 causes hypertrophic cardiomyopathy by dysregulating mTOR signaling
Authors: Schramm Christine , Fine Deborah M. , Edwards Michelle A. , Reeb Ashley N. , Krenz Maike
Published: November 2011

The identification of mutations in PTPN11 (encoding the protein tyrosine phosphatase Shp2) in families with congenital heart disease has facilitated mechanistic studies of various cardiovascular defects. However, the roles of normal and mutant Shp2 in the developing heart are still poorly understood. Furthermore, it remains unclear how Shp2 loss-of-function (LOF) mutations cause LEOPARD Syndrome (also termed Noonan Syndrome with multiple lentigines), which is characterized by congenital heart defects such as pulmonary valve stenosis and hypertrophic cardiomyopathy (HCM). In normal hearts, Shp2 controls cardiomyocyte size by regulating signaling through protein kinase B (Akt) and mammalian target of rapamycin (mTOR). We hypothesized that Shp2 LOF mutations dysregulate this pathway, resulting in HCM. For our studies, we chose the Shp2 mutation Q510E, a dominant-negative LOF mutation associated with severe early onset HCM. Newborn mice with cardiomyocyte-specific overexpression of Q510E-Shp2 starting before birth displayed increased cardiomyocyte sizes, heart-to-body weight ratios, interventricular septum thickness, and cardiomyocyte disarray. In 3-mo-old hearts, interstitial fibrosis was detected. Echocardiographically, ventricular walls were thickened and contractile function was depressed. In ventricular tissue samples, signaling through Akt/mTOR was hyperactivated, indicating that the presence of Q510E-Shp2 led to upregulation of this pathway. Importantly, rapamycin treatment started shortly after birth rescued the Q510E-Shp2-induced phenotype in vivo. If rapamycin was started at 6 wk of age, HCM was also ameliorated. We also generated a second mouse model in which cardiomyocyte-specific Q510E-Shp2 overexpression started after birth. In contrast to the first model, these mice did not develop HCM. In summary, our studies establish a role for mTOR signaling in HCM caused by Q510E-Shp2. Q510E-Shp2 overexpression in the cardiomyocyte population alone was sufficient to induce the phenotype. Furthermore, the pathomechanism was triggered pre- but not postnatally. However, postnatal rapamycin treatment could still reverse already established HCM, which may have important therapeutic implications.
Current perspectives on cardiac amyloidosis
Authors: Guan Jian , Mishra Shikha , Falk Rodney H. , Liao Ronglih
Published: November 2011

Amyloidosis represents a group of diseases in which proteins undergo misfolding to form insoluble fibrils with subsequent tissue deposition. While almost all deposited amyloid fibers share a common nonbranched morphology, the affected end organs, clinical presentation, treatment strategies, and prognosis vary greatly among this group of diseases and are largely dependent on the specific amyloid precursor protein. To date, at least 27 precursor proteins have been identified to result in either local tissue or systemic amyloidosis, with nine of them manifesting in cardiac deposition and resulting in a syndrome termed “cardiac amyloidosis” or “amyloid cardiomyopathy.” Although cardiac amyloidosis has been traditionally considered to be a rare disorder, as clinical appreciation and understanding continues to grow, so too has the prevalence, suggesting that this disease may be greatly underdiagnosed. The most common form of cardiac amyloidosis is associated with circulating amyloidogenic monoclonal immunoglobulin light chain proteins. Other major cardiac amyloidoses result from a misfolding of products of mutated or wild-type transthyretin protein. While the various cardiac amyloidoses share a common functional consequence, namely, an infiltrative cardiomyopathy with restrictive pathophysiology leading to progressive heart failure, the underlying pathophysiology and clinical syndrome varies with each precursor protein. Herein, we aim to provide an up-to-date overview of cardiac amyloidosis from nomenclature to molecular mechanisms and treatment options, with a particular focus on amyloidogenic immunoglobulin light chain protein cardiac amyloidosis.
Rapamycin Induces Bad Phosphorylation in Association with Its Resistance to Human Lung Cancer Cells
Authors: Liu Yan , Sun Shi-Yong , Owonikoko Taofeek K. , Sica Gabriel L. , Curran Walter J. , Khuri Fadlo R. , Deng Xingming
Published: November 2011

Inhibition of mTOR signaling by rapamycin has been shown to activate extracellular signal-regulated kinase 1 or 2 (ERK1/2) and Akt in various types of cancer cells, which contributes to rapamycin resistance. However, the downstream effect of rapamycin-activated ERKs and Akt on survival or death substrate(s) remains unclear. We discovered that treatment of human lung cancer cells with rapamycin results in enhanced phosphorylation of Bad at serine (S) 112 and S136 but not S155 in association with activation of ERK1/2 and Akt. A higher level of Bad phosphorylation was observed in rapamycin-resistant cells compared with parental rapamycin-sensitive cells. Thus, Bad phosphorylation may contribute to rapamycin resistance. Mechanistically, rapamycin promotes Bad accumulation in the cytosol, enhances Bad/14-3-3 interaction, and reduces Bad/Bcl-XL binding. Rapamycin-induced Bad phosphorylation promotes its ubiquitination and degradation, with a significant reduction of its half-life (i.e., from 53.3–37.5 hours). Inhibition of MEK/ERK by PD98059 or depletion of Akt by RNA interference blocks rapamycin-induced Bad phosphorylation at S112 or S136, respectively. Simultaneous blockage of S112 and S136 phosphorylation of Bad by PD98059 and silencing of Akt significantly enhances rapamycin-induced growth inhibition in vitro and synergistically increases the antitumor efficacy of rapamycin in lung cancer xenografts. Intriguingly, either suppression of Bad phosphorylation at S112 and S136 sites or expression of the nonphosphorylatable Bad mutant (S112A/S136A) can reverse rapamycin resistance. These findings uncover a novel mechanism of rapamycin resistance, which may promote the development of new strategies for overcoming rapamycin resistance by manipulating Bad phosphorylation at S112 and S136 in human lung cancer. Mol Cancer Ther; 11(1); 45–56. ©2011 AACR.
PI3K and STAT3: A New Alliance
Authors: Vogt Peter K. , Hart Jonathan Ross
Published: November 2011

Recent proteomic data have uncovered an interdependence of PI3K (phosphatidylinositol 3-kinase) and STAT3. In PI3K-transformed murine cells, STAT3 is phosphorylated on Y705 and activated in a PI3K-dependent manner, and dominant-negative STAT3 interferes with PI3K-induced oncogenic transformation. Phosphorylation of STAT3 in PI3K-transformed murine cells is mediated by the TEC (tyrosine kinase expressed in hepatocellular carcinoma) kinase BMX (bone marrow tyrosine kinase gene in chromosome X) and observations in glioblastoma stem cells reveal similar critical roles for STAT3 and BMX. These new data document an important role of STAT3 in PI3K-driven oncogenic transformation and mark BMX as a promising therapeutic target that could enhance the effectiveness of PI3K inhibitors.

Significance: The PI3K–TOR and STAT3 signaling pathways represent two distinct regulatory networks. The discovery of a functional link between these pathways is significant for our understanding of PI3K- and STAT3-driven oncogenic mechanisms and identifies the TEC kinase BMX as a new cancer target. Cancer Discovery; 1(6); 481–86. ©2011 AACR.
Relation of Lipid Gene Scores to Longitudinal Trends in Lipid Levels and Incidence of Abnormal Lipid Levels Among Individuals of European Ancestry
Authors: Lutsey Pamela L. , Rasmussen-Torvik Laura J. , Pankow James S. , Alonso Alvaro , Smolenski Derek J. , Tang Weihong , Coresh Josef , Volcik Kelly A. , Ballantyne Christie M. , Boerwinkle Eric , Folsom Aaron R.
Published: November 2011

Background—

Multiple genetic loci have been associated with blood lipid levels. We tested the hypothesis that persons with an unfavorable lipid gene profile would experience a greater increase in lipid levels and a higher incidence of abnormal lipid levels relative to those with more-favorable lipid gene profiles.

Methods and Results—

A total of 9328 individuals of European descent (aged 45–64 years) in the ARIC (Atherosclerosis Risk in Communities) study were followed for 9 years. Separate gene scores were created for each lipid phenotype on the basis of 95 loci identified in a published genome-wide association study of >100 000 people of European-descent. Adjusted linear and survival models were used to estimate associations with lipid levels and incidence of lipid-lowering medication or abnormal lipid levels. Age and sex interactions were also explored. The cross-sectional difference (mg/dL) per 1 SD was −1.89 for high-density lipoprotein cholesterol (HDL-C), 9.5 for low-density lipoprotein cholesterol (LDL-C), and 22.8 for triglycerides (
P
<5×10
−34
for all). Longitudinally, overall triglyceride levels rose over time, and each 1-SD greater triglyceride gene score was associated with an average increase in triglyceride levels of 0.3 mg/dL (
P
=0.003) over 3 years. The HDL-C, LDL-C, and total cholesterol gene scores were not related to change. All lipid gene scores were positively related to incidence of abnormal lipid levels over follow-up (hazard ratios per SD range, 1.15–1.36).

Conclusions—

Associations of genetic variants with lipid levels over time are complex. The triglyceride gene score was positively related to change in triglycerides levels, but similar longitudinal results were not observed for LDL-C or HDL-C levels. Unfavorable gene scores were nevertheless related to higher incidence of abnormal levels.
Rapid Estrogenic Effects on TMJ-responsive Brainstem Neurons
Authors: Tashiro A. , Okamoto K. , Bereiter D.A.
Published: November 2011

Estrogen status is a risk factor for temporomandibular muscle and joint disorders (TMJD) and other craniofacial pain conditions. The basis for estrogen modulation of pain is poorly understood and has often been attributed to long-term genomic effects. However, estrogens also act rapidly through membrane-initiated mechanisms to alter neural activity. To assess if estrogens act rapidly to affect TMJ-responsive neurons, we applied 17β-estradiol (E2) directly at the spinomedullary (Vc/C1-2) region, the initial brainstem site for synaptic integration of TMJ sensory signals, while recording single neuron activity. In ovariectomized female rats, E2 rapidly (within 10 minutes) and reversibly reduced TMJ-evoked neural activity at the Vc/C1-2 region. The effect was estrogen receptor (ER) subtype-specific, since ERβ agonists inhibited, while an ERβ agonist enhanced, evoked activity. A membrane-mediated mechanism was indicated, since the membrane-impermeable analogue, E2-BSA, mimicked the inhibitory effect of E2 and was prevented by an ER antagonist. This study demonstrated that E2 acted rapidly, through membrane-mediated pathways, and locally at the Vc/C1-2 region, to modulate sensory signals from the TMJ region. These results were consistent with the hypothesis that estrogens can act rapidly at the level of the trigeminal brainstem complex to influence sensory integration of TMJ-related information.
The Speed of Articulatory Movements Involved in Speech Production in Children With Dyslexia
Authors: Duranovic Mirela , Sehic Sabina
Published: November 2011

A group of children with dyslexia (mean ages 9 and 14 years) was studied, together with group of children without dyslexia matched for age. Participants were monolingual native speakers of the Bosnian language with transparent orthography. In total, the diagnostic tests were performed with 41 children with dyslexia and 41 nondyslexic children. The participants were asked to produce monosyllables, /pa/, /ta/, and /ka/, and the trisyllable /pataka/, as fast as possible. Analysis was undertaken in four ways: (1) time of occlusion duration for plosives (duration of stop), (2) voice onset time for plosives, (3) diadochokinetic rate—articulators rate measured by pronunciation of monosyllables and the trisyllable, and (4) time of moving articulators from one gesture to another—time of interval length (from the explosion of one plosive to the start of the explosion of another plosive). The results suggest that children with dyslexia have significant problems with the speed of articulatory movements involved in speech production.
Adults With Reading Disabilities
Authors: Swanson H. Lee
Published: November 2011

This article reviews the results of a meta-analysis of the experimental published literature that compares the academic, cognitive, and behavioral performance of adults with reading disabilities (RD) with average achieving adult readers. The meta-analysis shows that deficits independent of the classification measures emerged for adults with RD on measures of vocabulary, math, spelling, and specific cognitive process related to naming speed, phonological processing, and verbal memory. The results also showed that adults with high verbal IQs (scores > 100) but low word recognition standard scores (< 90) yielded greater deficits related to their average reading counterparts when compared to studies that included adults with RD with verbal IQ and reading scores in the same low range. Implications of the findings related to assessment and intervention are discussed.
Intergenerational Music Making
Authors: de Vries Peter
Published: November 2011

Three older Australians’ active engagement in music making with children was examined in this phenomenological study. Intergenerational music engagement was explored, focusing on the perspectives of the older Australians engaged in these musical interactions and, in particular, perceived benefits in being part of these musical interactions. Data were gathered through a series of open-ended, one-on-one interviews. Analysis of the data revealed five key themes about intergenerational (IG) music engagement: (1) IG music experiences promoted social engagement; (2) IG music experiences fostered the development of positive attitudes about young people; (3) choice in music making was valued in the IG music experiences; (4) involvement in IG music experiences resulted in the older Australians feeling valued and respected; and (5) there was the perception of reciprocity in the learning that occurred in the IG music experiences. Implications of intergenerational music engagement for music education are discussed.
The Free Breakfast Effect
Authors: Nicolau Juan L. , Sellers Ricardo
Published: November 2011

This article presents the first evidence of the zero price effect in tourism. The multicomponent nature of tourism products adds complexity to the price-setting process, but also allows managers to take advantage of the interrelationships among the different components to maximize sales. Taking the zero price model, the authors adapt and apply it to a two-component tourism product. The experiments conducted show evidence in favor of the free breakfast effect: even though people lean toward their preferred, more expensive alternative, when the cheaper option offers a free breakfast, the demand for the latter increases and for the former it decreases. This result shows that the zero price effect is not confined to single products but also applies in multicomponent contexts. Important managerial implications in the realm of sales promotion policies are drawn.
Generating test reference years from the UKCP09 projections and their application in building energy simulations
Authors: Du H , Underwood CP , Edge JS
Published: November 2011

In this study, test reference year (TRY) data for three UK cities are generated from the new UKCP09 climate change projections 1 for a variety of future time horizons and carbon emission scenario assumptions. The data are applied to the energy simulation of three commercial buildings and one house for the three city locations (London, Manchester and Edinburgh), three future time horizons in this century and three carbon emission scenarios. Results are compared with those generated using alternative TRYs from two other research groups who used UKCP09 1 as well as with the existing TRY data sets which form the CIBSE Future Weather Years 2 in order to produce robust results. Results of future simulations of peak summer operative temperatures, peak cooling demand, annual cooling energy, peak heating demand and annual heating energy are presented for the four building case studies benchmarked against control weather data for the period 1960–1989. The results show increasing internal operative temperatures (non-air-conditioned) and increasing air-conditioning demands (air-conditioned) throughout this century and though peak heating demands remain similar to control data, annual heating energy consumptions can be expected to fall sharply.

Practical applications: Currently, practitioners can use Test Reference Years for use in building energy simulations. In 2009, the CIBSE released Future Weather Years, which go further by allowing practitioners to explore the thermal and comfort behaviour of buildings at future time horizons thus helping to ‘future proof’ a design. In 2009, the United Kingdom Climate Impacts Programme released a new generation of climate change scenario data (the UKCP09 climate change projections) using probabilistic methods. These are the most comprehensive data yet and provides a greater degree of detail than was available to generate the CIBSE Future Weather Years. It is therefore likely that the new data will gradually become the normal basis for investigating future building thermal and comfort response. In this study, a sample of TRY is generated from the UKCP09 data and applied to the simulation of a sample of ‘real’ buildings. The results are compared with both the existing CIBSE Future Weather Years as well as with Test Reference Years generated using UKCP09 by two other research groups. The results provide a robust way forward for simulating building thermal and comfort response using future weather data.
Outcomes of Absence Control Initiatives
Authors: Johnson Michael D. , Holley Erica C. , Morgeson Frederick P. , LaBonar Deborah , Stetzer Adam
Published: November 2011

Although considerable research has examined various antecedents of employee absence, relatively little research has examined the effects of organizational absence control initiatives on different types of absence, or how differences in employee perceptions of these initiatives may influence employee absences. Through the lens of organizational justice, the authors address this gap in the literature by tracking absenteeism in two manufacturing plants that implemented, at different times, absence control initiatives designed to increase the salience of absence outcomes via explicit rewards and punishments. Results showed that the policy changes had the intended effect of reducing casual absence, but also the unintended effect of increasing Family and Medical Leave Act (FMLA) absence. The results for disability-based absence were mixed. Individual employee perceptions of both the salience of absence outcomes and the fairness of the absence policies showed differential effects on casual and FMLA absence. These perceptions interacted such that employees who perceived the policies to be more salient and unfair had the highest instances of FMLA absence. Implications for absence and justice research and practice are discussed.
Prevalence of Musculoskeletal Injuries in Swedish Elite Track and Field Athletes
Authors: Jacobsson Jenny , Timpka Toomas , Kowalski Jan , Nilsson Sverker , Ekberg Joakim , Renström Per
Published: November 2011

Background: Little is known of injury patterns in track and field (athletics). Injury prevalence has been proposed as the most appropriate measure of the injury rate in sports where athletes are at risk for overuse problems.

Purpose: To ascertain 1-year retrospective and current prevalence of injury in elite track and field athletes to help plan injury prevention programs for this sport.

Study Design: Descriptive epidemiology study.

Methods: Two hundred seventy-eight youth (16 years old) and adult athletes from an eligible study population of 321 athletes were included.

Results: The 1-year retrospective injury prevalence was 42.8% (95% confidence interval [CI], 36.9%-49.0%); the point prevalence was 35.4% (95% CI, 29.7%-41.4%). The diagnosis group displaying the highest injury prevalence was inflammation and pain in the gradual onset category (1-year prevalence, 20.9%; 95% CI, 16.2%-26.2%; and point prevalence, 23.2%; 95% CI, 18.4%-28.7%). A strong tendency for higher 1-year prevalence of 16.5% (95% CI, 12.2%-21.4%) than point prevalence of 8.5% (95% CI, 5.5%-12.5%) was recorded for sudden onset injuries in the diagnosis group sprain, strain, and rupture. The body region showing the highest injury prevalence was the knee and lower leg with 15.0% (95% CI, 11.0%-19.8%) 1-year prevalence and 13.7% (95% CI, 9.8%-18.3%) point prevalence, followed by the Achilles tendon, ankle, and foot/toe with 11.7% (95% CI, 8.2%-16.1%) 1-year prevalence and 11.4% (95% CI, 7.9%-15.8%) point prevalence.

Conclusion: The injury prevalence is high among Swedish elite track and field athletes. Most of the injuries affect the lower extremities and are associated with a gradual onset. Although it is associated with a potential recall bias, the 1-year retrospective prevalence measure captured more sudden onset injuries than the point prevalence measure. Future prospective studies in track and field are needed to identify groups of athletes at increased risk.
Bleeding Risk Secondary to Deep Vein Thrombosis Prophylaxis in Patients With Lower Gastrointestinal Bleeding
Authors: Deutsch Gary B. , Kandel Anuj R. , Knobel Denis , Gupta Rajeev , Ritter Garry , Marini Corrado P. , Barrera Rafael
Published: November 2011

Introduction:

Deep vein thrombosis (DVT) and pulmonary embolism (PE) continue to pose a major burden on the health care system in the United States. The precise timing of anticoagulation initiation in critically ill patients with recent or active lower gastrointestinal bleeding (LGIB) is not well defined. We set out to study the safety and efficacy of early heparin administration for DVT prophylaxis in these patients.

Methods:

A review of all patients admitted to the ICU with a diagnosis of LGIB over a 13-year period was performed. A total of 60 patients received subcutaneous heparin along with mechanical prophylaxis, whereas 59 patients had intermittent pneumatic compression devices alone.

Results:

There was no difference in morbidity or mortality between the groups who received heparin and the nonheparin cohort. Neither of the groups developed a DVT or PE during the study period. Patients who received heparin had a median ICU LOS of 3 days, when compared with 2 days for patients who did not receive heparin ( P < .0118). There was a significant association between units of blood received during the first 24 hours in the ICU and heparin usage ( P < .0229). Those administered heparin received more units (median 3) than those who did not receive heparin (median 2).

Conclusions:

Administration of subcutaneous heparin increases the transfusion requirements and LOS in ICU patients with LGIB. After 24 hours, however, the blood transfusion requirements are equivalent. DVT prophylaxis in patients with a diagnosis of LGIB should be initiated after 24 hours of ICU admission.
Determinants of Exclusive Breastfeeding in a Cohort of Primiparous Periurban Peruvian Mothers
Authors: Matias Susana L. , Nommsen-Rivers Laurie A. , Dewey Kathryn G.
Published: November 2011

The authors aimed to identify factors associated with exclusive breastfeeding (EBF) among 117 Peruvian mothers planning to breastfeed exclusively. Data were collected on days 0 and 3, and months 1, 3, and 6. Exclusive breastfeeding status was evaluated with a 24-hour recall of infant diet. Exclusive breastfeeding rates were 74%, 72%, and 35% at 1, 3, and 6 months, respectively. At 3 months, lower maternal education, greater breastfeeding frequency (day 3), greater breast pain (day 3), and depot medroxyprogesterone acetate use (3 months) were associated with EBF, after adjusting for EBF intentions. At 6 months, greater infant birth weight and mother–not employed were associated with EBF, after controlling for EBF intentions. More educated and working mothers, and infants with lower birth weight should be targeted in interventions to promote EBF in urban Peru. Research is also warranted to explore the factors linking depot medroxyprogesterone acetate use and breast pain with EBF duration.
Sick Body, Vigilant Mind
Authors: Miller Saul L. , Maner Jon K.
Published: November 2011

Activation of the behavioral immune system has been shown to promote activation of the biological immune system. The current research tested the hypothesis that activation of the biological immune system (as a result of recent illness) promotes activation of the behavioral immune system. Participants who had recently been ill, and had therefore recently experienced activation of their biological immune system, displayed heightened attention to (Study 1) and avoidance of (Study 2) disfigured individuals—cognitive and behavioral processes reflecting activation of the behavioral immune system. These findings shed light on the interactive nature of biological and psychological mechanisms designed to help people overcome the threat of disease.
Quality of Life in Patients With Advanced Lung Cancer Treated at Home and at a Palliative Care Unit
Authors: Leppert Wojciech , Turska Anna , Majkowicz Mikolaj , Dziegielewska Sylwia , Pankiewicz Piotr , Mess Eleonora
Published: November 2011

Background: To assess quality of life (QOL) in patients with advanced lung cancer. Patients and Methods: A prospective study of 78 patients cared at home and at a palliative care unit (PCU) with 2 QOL assessments was conducted. Results: Fifty patients completed the study. In the EORTC QLQ-C30 role, cognitive, social functioning, global QOL, fatigue, pain, dyspnea, and appetite deteriorated; nausea/vomiting improved; dyspnea was more intense in the case of in-home patients. In the EORTC QLQ-LC13 hemoptysis improved; pain in other parts was more intense in the PCU patients. Pain (Visual Analogue scale) was more intense in the PCU patients; the level of activity (Karnofsky) decreased in the case of patients treated at home. Conclusions: QOL deteriorated with few differences between home and the PCU patients.
Spoken and Written Narratives in Swedish Children and Adolescents With Hearing Impairment
Authors: Asker-Árnason Lena , Åkerlund Viktoria , Skoglund Cecilia , Ek-Lagergren Ingela , Wengelin Åsa , Sahlén Birgitta
Published: November 2011

Twenty 10- to 18-year-old children and adolescents with varying degrees of hearing impairment (HI) and hearing aids (HA), ranging from mild-moderate to severe, produced picture-elicited narratives in a spoken and written version. Their performance was compared to that of 63 normally hearing (NH) peers within the same age span. The participants with HI and NH showed similar patterns regarding intragroup correlations between corresponding measures of spoken and written narratives. However, the participants with HI had significantly less diverse language than the NH group. The participants with poorer hearing (higher best ear hearing level [BEHL]) produced spoken and written narratives comprising more content words and they also produced written narratives that were less lexically diverse than the participants with better hearing (lower BEHL). The difference as to lexical skills emphasizes the importance of focusing on these skills in the group of children with HI. However, the results give support for a quite optimistic view on the development of narration in children with HI with HA, at least for picture-elicited narratives.
Health Implications of a Vegetarian Diet
Authors: Marsh Kate , Zeuschner Carol , Saunders Angela
Published: November 2011

There is now a significant amount of research that demonstrates the health benefits of vegetarian and plant-based diets, which have been associated with a reduced risk of obesity, diabetes, heart disease, and some types of cancer as well as increased longevity. Vegetarian diets are typically lower in fat, particularly saturated fat, and higher in dietary fiber. They are also likely to include more whole grains, legumes, nuts, and soy protein, and together with the absence of red meat, this type of eating plan may provide many benefits for the prevention and treatment of obesity and chronic health problems, including diabetes and cardiovascular disease. Although a well-planned vegetarian or vegan diet can meet all the nutritional needs of an individual, it may be necessary to pay particular attention to some nutrients to ensure an adequate intake, particularly if the person is on a vegan diet. This article will review the evidence for the health benefits of a vegetarian diet and also discuss strategies for meeting the nutritional needs of those following a vegetarian or plant-based eating pattern.
Benefits and Barriers to Healthful Eating
Authors: Soliah Lu Ann Laurice , Walter Janelle Marshall , Jones Sheila Ann
Published: November 2011

A lack of cooking skills and reduced food preparation knowledge are significant barriers to the production of home cooked meals in the United States. The benefits and barriers to healthful eating in relationship to decreased food preparation ability are summarized in this review. In particular, home food preparation barriers, the consequences that result from eating out frequently, and the benefits of home-produced meals are presented. Strategies for preparing meals at home and specific recommendations for health care professionals are presented in this article.
Characteristic Markers of the WNT Signaling Pathways Are Differentially Expressed in Osteoarthritic Cartilage
Authors: Thorfve A. , Dehne T. , Lindahl A. , Brittberg M. , Pruss A. , Ringe J. , Sittinger M. , Karlsson C.
Published: November 2011

Objective:

It is well known that expression of markers for WNT signaling is dysregulated in osteoarthritic (OA) bone. However, it is still not fully known if the expression of these markers also is affected in OA cartilage. The aim of this study was therefore to examine this issue.

Methods:

Human cartilage biopsies from OA and control donors were subjected to genome-wide oligonucleotide microarrays. Genes involved in WNT signaling were selected using the BioRetis database, KEGG pathway analysis was searched using DAVID software tools, and cluster analysis was performed using Genesis software. Results from the microarray analysis were verified using quantitative real-time PCR and immunohistochemistry. In order to study the impact of cytokines for the dysregulated WNT signaling, OA and control chondrocytes were stimulated with interleukin-1 and analyzed with real-time PCR for their expression of WNT-related genes.

Results:

Several WNT markers displayed a significantly altered expression in OA compared to normal cartilage. Interestingly, inhibitors of the canonical and planar cell polarity WNT signaling pathways displayed significantly increased expression in OA cartilage, while the Ca2+/WNT signaling pathway was activated. Both real-time PCR and immunohistochemistry verified the microarray results. Real-time PCR analysis demonstrated that interleukin-1 upregulated expression of important WNT markers.

Conclusions:

WNT signaling is significantly affected in OA cartilage. The result suggests that both the canonical and planar cell polarity WNT signaling pathways were partly inhibited while the Ca2+/WNT pathway was activated in OA cartilage.
One-Year Clinical and Radiological Results of a Prospective, Investigator-Initiated Trial Examining a Novel, Purely Autologous 3-Dimensional Autologous Chondrocyte Transplantation Product in the Knee
Authors: Fickert Stefan , Gerwien Philip , Helmert Benjamin , Schattenberg Torsten , Weckbach Sabine , Kaszkin-Bettag Marietta , Lehmann Lars
Published: November 2011

Background:

The 3-dimensional autologous chondrocyte transplantation (ACT3D) comprises isolation of chondrocytes from cartilage biopsies, cultivation to spheroids, and transplantation into the cartilage defect.

Objectives:

To evaluate the patients’ general health and functionality and to assess the defect repair after ACT3D with spheroids by MRI and MOCART scoring.

Methods:

Thirty-seven patients with isolated chondral lesions of the knee underwent ACT3D with spheroids through medial arthrotomy. Patient-administered scores were assessed at baseline (day before transplantation), at 6 weeks, and at 3, 6, and 12 months. MRI and MOCART scoring were performed at 3 and 12 months after ACT3D.

Results:

Patients were diagnosed with full-thickness patellofemoral ( n = 16), femoral condylar ( n = 18), or both defect types ( n = 3), International Cartilage Repair Society (ICRS) grade 3 or 4, with defect sizes between 1.0 and 12.0 cm2. On average, 59.5 spheroids/cm2 in defect size were transplanted. An overall statistically significant improvement from baseline to 12 months was observed for all assessment scores (Lysholm, International Knee Documentation Committee [IKDC], SF-36, Tegner) combined with a significant reduction in the visual analog scale (VAS) for pain and an advanced defect filling. Subgroup analyses revealed a positive clinical outcome independent on defect size, defect locations, spheroid dosage, age, duration of symptoms, and severity of complaints at baseline. Seven patients experienced in total 8 adverse events, of which knee joint effusion and blocking were assessed as possibly or probably related to ACT3D.

Conclusions:

The patient-administered assessment scores along with the fast defect filling with ACT3D using spheroids demonstrated an increase in activity level and quality of life after a 1-year follow-up.
A novel hybrid CFH/CFHR3 gene generated by a microhomology-mediated deletion in familial atypical hemolytic uremic syndrome
Authors: Francis Nigel J. , McNicholas Bairbre , Awan Atif , Waldron Mary , Reddan Donal , Sadlier Denise , Kavanagh David , Strain Lisa , Marchbank Kevin J. , Harris Claire L. , Goodship Timothy H. J.
Published: November 2011

Genomic disorders affecting the genes encoding factor H (fH) and the 5 factor H related proteins have been described in association with atypical hemolytic uremic syndrome. These include deletions of CFHR3, CFHR1, and CFHR4 in association with fH autoantibodies and the formation of a hybrid CFH/CFHR1 gene. These occur through nonallelic homologous recombination secondary to the presence of large segmental duplications (macrohomology) in this region. Using multiplex ligation-dependent probe amplification to screen for such genomic disorders, we have identified a large atypical hemolytic uremic syndrome family where a deletion has occurred through microhomology-mediated end joining rather than nonallelic homologous recombination. In the 3 affected persons of this family, we have shown that the deletion results in formation of a CFH/CFHR3 gene. We have shown that the protein product of this is a 24 SCR protein that is secreted with normal fluid-phase activity but marked loss of complement regulation at cell surfaces despite increased heparin binding. In this study, we have therefore shown that microhomology in this area of chromosome 1 predisposes to disease associated genomic disorders and that the complement regulatory function of fH at the cell surface is critically dependent on the structural integrity of the whole molecule.
Interaction of HTLV-1 Tax with minichromosome maintenance proteins accelerates the replication timing program
Authors: Boxus Mathieu , Twizere Jean-Claude , Legros Sébastien , Kettmann Richard , Willems Luc
Published: November 2011

The Tax oncoprotein encoded by the human T-cell leukemia virus type 1 plays a pivotal role in viral persistence and pathogenesis. Human T-cell leukemia virus type 1–infected cells proliferate faster than normal lymphocytes, expand through mitotic division, and accumulate genomic lesions. Here, we show that Tax associates with the minichromosome maintenance MCM2-7 helicase complex and localizes to origins of replication. Tax modulates the spatiotemporal program of origin activation and fires supplementary origins at the onset of S phase. Thereby, Tax increases the DNA replication rate, accelerates S phase progression, but also generates a replicative stress characterized by the presence of genomic lesions. Mechanistically, Tax favors p300 recruitment and histone hyperacetylation at late replication domains, advancing their replication timing in early S phase.
Allelic methylation levels of the noncoding VTRNA2-1 located on chromosome 5q31.1 predict outcome in AML
Authors: Treppendahl Marianne Bach , Qiu Xiangning , Søgaard Alexandra , Yang Xiaojing , Nandrup-Bus Cecilie , Hother Christoffer , Andersen Mette Klarskov , Kjeldsen Lars , Möllgaard Lars , Hellström-Lindberg Eva , Jendholm Johan , Porse Bo T. , Jones Peter A. , Liang Gangning , Grønbæk Kirsten
Published: November 2011

Deletions of chromosome 5q are associated with poor outcomes in acute myeloid leukemia (AML) suggesting the presence of tumor suppressor(s) at the locus. However, definitive identification of putative tumor suppressor genes remains controversial. Here we show that a 106-nucleotide noncoding RNA vault RNA2-1 (vtRNA2-1), previously misannotated as miR886, could potentially play a role in the biology and prognosis of AML. vtRNA2-1 is transcribed by polymerase III and is monoallelically methylated in 75% of healthy individuals whereas the remaining 25% of the population have biallelic hypomethylation. AML patients without methylation of VTRNA2-1 have a considerably better outcome than those with monoallelic or biallelic methylation (n = 101, P = .001). We show that methylation is inversely correlated with vtRNA2-1 expression, and that 5-azanucleosides induce vtRNA2-1 and down-regulate the phosphorylated RNA-dependent protein kinase (pPKR), whose activity has been shown to be modulated by vtRNA2-1. Because pPKR promotes cell survival in AML, the data are consistent with vtRNA2-1 being a tumor suppressor in AML. This is the first study to show that vtRNA2-1 might play a significant role in AML, that it is either mono- or biallelically expressed in the blood cells of healthy individuals, and that its methylation state predicts outcome in AML.
Effectiveness of Motivational Interviewing in improving lipid level in patients with dyslipidemia assisted by general practitioners: Dislip-EM study protocol
Authors: Pérula Luis A , Bosch Josep M , Bóveda Julia , Campiñez Manuel , Barragán Nieves , Arboniés Juan C , Prados Jose A , Martín Enrique , Martín Remedios , Massons Josep , Criado Margarita , Ruiz Roger , Fernández José A , Buitrago Francisco , Olaya Inmaculada , Pérez Modesto , Ruiz Joaquin
Published: November 2011

Background

The non-pharmacological approach to cholesterol control in patients with hyperlipidemia is based on the promotion of a healthy diet and physical activity. Thus, to help patients change their habits, it is essential to identify the most effective approach. Many efforts have been devoted to explain changes in or adherence to specific health behaviors. Such efforts have resulted in the development of theories that have been applied in prevention campaigns, and that include brief advice and counseling services. Within this context, Motivational Interviewing has proven to be effective in changing health behaviors in specific cases. However, more robust evidence is needed on the effectiveness of Motivational Interviewing in treating chronic pathologies -such as dyslipidemia- in patients assisted by general practitioners. This article describes a protocol to assess the effectiveness of MI as compared with general practice (brief advice), with the aim of improving lipid level control in patients with dyslipidemia assisted by a general practitioner.

Methods/Design

An open, two-arm parallel, multicentre, cluster, controlled, randomized, clinical trial will be performed. A total of 48-50 general practitioners from 35 public primary care centers in Spain will be randomized and will recruit 436 patients with dyslipidemia. They will perform an intervention based either on Motivational Interviewing or on the usual brief advice. After an initial assessment, follow-ups will be performed at 2, 4, 8 and 12 months. Primary outcomes are lipid levels (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) and cardiovascular risk. The study will assess the degree of dietary and physical activity improvement, weight loss in overweight patients, and adherence to treatment guidelines.

Discussion

Motivational interview skills constitute the primary strategies GPs use to treat their patients. Having economical, simple, effective and applicable techniques is essential for primary care professionals to help their patients change their lifestyle and improve their health. This study will provide scientific evidence on the effectiveness of Motivational interviewing, and will be performed under strict control over the data collected, ensuring the maintenance of therapeutic integrity.

Trials Registration

ClinicalTrials.gov (NCT01282190).
Pleural fluid soluble triggering receptor expressed on myeloid cells-1 as a marker of bacterial infection: a meta-analysis
Authors: Summah Hanssa , Tao Li-Li , Zhu Ying-Gang , Jiang Hong-Ni , Qu Jie-Ming
Published: November 2011

Background

Pleural infection is a common clinical problem. Its successful treatment depends on rapid diagnosis and early initiation of antibiotics. The measurement of soluble triggering receptor expressed in myeloid cells-1 (sTREM-1) level in pleural effusions has proven to be a valuable diagnostic tool for differentiating bacterial effusions from effusions of other etiologies. Herein, we performed a meta-analysis to assess the accuracy of pleural fluid sTREM-1 in the diagnosis of bacterial infection.

Methods

We searched Web of Knowledge and Medline from 1990 through March 2011 for studies reporting diagnostic accuracy data regarding the use of sTREM-1 in the diagnosis of bacterial pleural effusions. Pooled sensitivity and specificity and summary measures of accuracy and Q* were calculated.

Results

Overall, the sensitivity of sTREM-1was 78% (95% CI: 72%-83%); the specificity was 84% (95% CI: 80%-87%); the positive likelihood ratio was 6.0 (95% CI: 3.3-10.7); and the negative likelihood ratio was 0.22 (95% CI: 0.12-0.40). The area under the SROC curve for sTREM-1 was 0.92. Statistical heterogeneity and inconsistency were found for sensitivity (p = 0.015, χ2 = 15.73, I2 = 61.9%), specificity (p = 0.000, χ2 = 29.90, I2 = 79.9%), positive likelihood ratio (p = 0.000, χ2 = 33.09, I2 = 81.9%), negative likelihood ratio (p = 0.008, χ2 = 17.25, I2 = 65.2%), and diagnostic odds ratio (p = 0.000, χ2 = 28.49, I2 = 78.9%). A meta-regression analysis performed showed that the Quality Assessment of Diagnostic Accuracy Studies score (p = 0.3245; RDOR, 4.34; 95% CI, 0.11 to 164.01), the Standards for Reporting of Diagnostic Accuracy score (p = 0.3331; RDOR, 1.70; 95% CI, 0.44 to 6.52), lack of blinding (p = 0.7439; RDOR, 0.60; 95% CI, 0.01 to 33.80), and whether the studies were prospective or retrospective studies (p = 0.2068; RDOR, 7.44; 95% CI, 0.18 to 301.17) did not affect the test accuracy. A funnel plot for publication bias suggested a remarkable trend of publication bias.

Conclusions

Our findings suggest that sTREM-1 has a good diagnostic accuracy and may provide a useful adjunctive tool for the diagnosis of bacterial pleural effusions. However, further studies are needed in order to identify any differences in the diagnostic performance of sTREM-1 of parapneumonic effusions and empyemas.
Specific Involvement of Atypical PKCξ/PKMξ in Spinal Persistent Nociceptive Processing following Peripheral Inflammation in Rat
Authors: Marchand Fabien , D'Mello Richard , Yip Ping K , Calvo Margarita , Muller Emilie , Pezet Sophie , Dickenson Anthony H , McMahon Stephen B
Published: November 2011

Background:

Central sensitization requires the activation of various intracellular signalling pathways within spinal dorsal horn neurons, leading to a lowering of activation threshold and enhanced responsiveness of these cells. Such plasticity contributes to the manifestation of chronic pain states and displays a number of features of longterm potentiation (LTP), a ubiquitous neuronal mechanism of increased synaptic strength. Here we describe the role of a novel pathway involving atypical PKCξ/PKMξ in persistent spinal nociceptive processing, previously implicated in the maintenance of late-phase LTP.

Results:

Using both behavioral tests and in vivo electrophysiology in rats, we show that inhibition of this pathway, via spinal delivery of a myristoylated protein kinase C-ξ pseudo-substrate inhibitor, reduces both pain-related behaviors and the activity of deep dorsal horn wide dynamic range neurons (WDRs) following formalin administration. In addition, Complete Freund's Adjuvant (CFA)-induced mechanical and thermal hypersensitivity was also reduced by inhibition of PKCξ/PKMξ activity. Importantly, this inhibition did not affect acute pain or locomotor behavior in normal rats and interestingly, did not inhibited mechanical allodynia and hyperalgesia in neuropathic rats. Pain-related behaviors in both inflammatory models coincided with increased phosphorylation of PKCξ/PKMξ in dorsal horn neurons, specifically PKMξ phosphorylation in formalin rats. Finally, inhibition of PKCξ/PKMξ activity decreased the expression of Fos in response to formalin and CFA in both superficial and deep laminae of the dorsal horn.

Conclusions:

These results suggest that PKCξ, especially PKMξ isoform, is a significant factor involved in spinal persistent nociceptive processing, specifically, the manifestation of chronic pain states following peripheral inflammation.
Laparoscopic myomectomy of a subserous pedunculated fibroid at 14 weeks of pregnancy: a case report
Authors: Ardovino Mario , Ardovino Italo , Castaldi Maria Antonietta , Monteverde Antonietta , Colacurci Nicola , Cobellis Luigi
Published: November 2011

Introduction

Uterine leiomyomas are seen in 1.6% to 4% of pregnancies. With the increasing age of obstetric patients, more cases are being encountered during pregnancy.

Case presentation

We report the case of a 31-year-old Caucasian woman with acute recurrent abdominal pain due to a subserous fundic myoma, measuring 48 × 52 × 63 mm, with an implantation base of 22 × 18 mm, which was successfully treated by laparoscopy at 14 weeks of pregnancy. At a gestational age of week 40, the patient spontaneously delivered a healthy 3216 g girl baby.

Conclusion

As far as we know, this is the first reported case of laparoscopic myomectomy this early during a pregnancy. Our experience together with an analysis of cases reported in the literature suggests that myomectomy during pregnancy may be considered safe, but only in the hands of experienced laparoscopic surgeons. There are a few reports in the literature about laparoscopic myomectomy during the first half of pregnancy that demonstrate its feasibility in selected cases. Some technical tools could improve the procedure with a minimum of risk for the ongoing pregnancy.