bluuebunny/crossref_metadata_2025 huggingface dataset:
Caveolin-1 expression during the progression of pulmonary hypertension
Authors: Huang Jing , Wolk John H , Gewitz Michael H , Mathew Rajamma
Published: August 2012

Caveolin-1 plays a pivotal role in maintaining vascular health. Progressive loss of endothelial caveolin-1 and activation of proliferative and anti-apoptotic pathways occur before the onset of monocrotaline (MCT)-induced pulmonary hypertension (PH), and the rescue of endothelial caveolin-1 attenuates PH. Recently, we reported endothelial caveolin-1 loss associated with enhanced expression of caveolin-1 in smooth muscle cells (SMC) with subsequent neointima formation in human PH. To examine whether the loss of endothelial caveolin-1 followed by an enhanced expression in SMC is a sequential event in the progression of PH, we studied rats at two and four weeks post-MCT. Right ventricular (RV) systolic pressure, RV hypertrophy, pulmonary vascular histology, and the expression of caveolin-1 and endothelial membrane proteins (platelet/endothelial cell adhesion molecule-1 [PECAM-1], both α and β subunits of soluble guanylate cyclase [sGC]), von Willebrand factor (vWF), smooth muscle α-actin, proliferative and anti-apoptotic factors (PY-STAT3 and Bcl-xL) and matrix metalloproteinase (MMP) 2 in the lungs were examined. PH was accompanied by a progressive loss of endothelial caveolin-1, activation of PY-STAT3, increased Bcl-xL expression and vascular remodeling at two and four weeks post-MCT. Loss of PECAM-1 and sGC (both subunits) paralleled that of caveolin-1, whereas vWF was well preserved at two weeks post-MCT. At four weeks post-MCT, 29% of the arteries showed a loss of vWF in addition to endothelial caveolin-1, and 70% of these arteries exhibited enhanced expression of caveolin-1 in SMC; and there was increased expression and activity of MMP2. In conclusion, MCT-induced endothelial injury disrupts endothelial cell membrane with a progressive loss of endothelial caveolin-1, and the activation of proliferative and antiapoptotic pathways leading to PH. Subsequent extensive endothelial cell damage results in enhanced expression of caveolin-1 in SMC. In addition, there is a progressive increase in MMP2 expression and activity. These alterations may further facilitate cell proliferation, matrix degradation and cell migration, thus contributing to the progression of the disease.
Coronary response to diadenosine triphosphate after ischemia–reperfusion in the isolated rat heart
Authors: García-Villalón Angel Luis , Fernández Nuria , Monge Luis , Granado Miriam , Carreño-Tarragona Gonzalo , Figueras Juan Carlos , Diéguez Godofredo
Published: August 2012

Diadenosine triphosphate (Ap3A) is a vasoactive mediator stored in platelet granules that may be released during coronary ischemia–reperfusion. To study its coronary effects in such circumstances, rat hearts were perfused in a Langendorff preparation and the coronary response to Ap3A (10−7–10−5 mol/L) was recorded. Both at basal coronary resting tone and after precontraction with 11-dideoxy-1a,9a-epoxymethanoprostaglandin F2 α (U46619), Ap3A produced concentration-dependent vasodilation in the heart, which was attenuated following ischemia–reperfusion. Ap3A-induced relaxation was also attenuated in control conditions and after ischemia–reperfusion by the purinergic P2Y antagonist reactive blue 2 (2 × 10−6 mol/L), the P2Y1 antagonist MRS 2179 (10−5 mol/L), the nitric oxide synthesis inhibitor N-omega-nitro-l-arginine methyl ester (l-NAME; 10−4 mol/L) and the ATP-dependent potassium channel blocker glibenclamide (10−5 mol/L). These results suggest that Ap3A induces coronary vasodilation, an effect attenuated by ischemia–reperfusion due to the functional impairment of purinergic P2Y receptors and KATP channels, and/or reduced nitric oxide release. This impairment of vasodilation may contribute to the coronary dysregulation that occurs during ischemia–reperfusion.
Erythrocyte membranes convert monomeric ferriprotoporphyrin IX to β-hematin in acidic environment at malarial fever temperature
Authors: Orjih Augustine U , Mathew Thazhumpal C , Cherian Preethi T
Published: August 2012

Hemozoin production makes it possible for intraerythrocytic malaria parasites to digest massive quantities of hemoglobin but still avoid potential ferriprotoporphyrin IX (FP) toxicity, which they cannot decompose further. Some antimalarial drugs, such as chloroquine, work by inhibiting this production, forcing the parasite to starve to death. As part of the efforts to identify possible biological mechanisms of FP polymerization, we have used normal human erythrocyte membranes as a model, to promote β-hematin ( β-h) synthesis. Hemin in 35% aqueous dimethyl sulfoxide (DMSO) was reacted with isolated erythrocyte membranes and incubated overnight in sodium acetate buffer, pH 4.8, at 41°C. Infrared spectroscopy and electron microscopy showed that β-h was produced. Hemin in 10% was less effective as the substrate than when it was in 35% DMSO. A high malarial temperature seemed to be necessary, because FP polymerization was less at 37°C than at 41°C. Production was partially inhibited by chloroquine. These observations are of interest because other investigators have reported that membrane lipids mediated FP polymerization, but whole membranes were ineffective. On the other hand, our hypothesis is that the transport vesicles (TV) in malaria parasites could provide the receptor for FP and the lipids that promote hemozoin formation. Erythrocyte membranes may not be directly involved, but Plasmodium species transport hemoglobin in membrane-bound TV into food vacuoles, where hemoglobin catabolism is completed and hemozoin crystals are stored.
Endeavour, altitude and risk: reflections on a lifetime of mountaineering and exploration
Authors: Clarke Charles
Published: August 2012

In July 2012 thousands of competitors from many nations arrive for the London Olympics, each striving to be a champion. Oh, the drive, resolve, heartache and pain. Our capital will be taken over, the press will both celebrate and criticize events; sponsorship deals will soon dominate the results. The men and women who are competing will have trained for many months or years, striven nationally and internationally, fighting hard for places in their teams. What drives them? This short paper is a personal perspective, unashamedly anecdotal, looking at some of the driving forces behind my own endeavours. I have spent a lifetime climbing mountains, with a focus on the exploration of remote regions. I also deal here with the physiological and medical challenges that high altitude mountaineering poses, and discuss its risks.
Failure to increase insulin secretory capacity during pregnancy-induced insulin resistance is associated with ethnicity and gestational diabetes
Authors: Mørkrid Kjersti , Jenum Anne K , Sletner Line , Vårdal Mari H , Waage Christin W , Nakstad Britt , Vangen Siri , Birkeland Kåre I
Published: August 2012

Objective

To assess changes in insulin resistance and β-cell function in a multiethnic cohort of women in Oslo, Norway, from early to 28 weeks' gestation and 3 monthspost partumand relate the findings to gestational diabetes mellitus (GDM).

Method

Population-based cohort study of 695 healthy pregnant women from Western Europe (41%), South Asia (25%), Middle East (15%), East Asia (6%) and elsewhere (13%). Blood samples and demographics were recorded at mean 15 (V1) and 28 (V2) weeks' gestation and 3 monthspost partum(V3). Universal screening was by 75 g oral glucose tolerance test at V2, GDM with modified IADPSG criteria (no 1-h measurement): fasting plasma glucose (PG) ≥5.1 or 2-h PG ≥8.5 mmol/l. Homeostatic model assessment (HOMA)-β (β-cell function) and HOMA-IR (insulin resistance) were calculated from fasting glucose and C-peptide.

Result

Characteristics were comparable across ethnic groups, except age (South Asians: younger,P<0.001) and prepregnant BMI (East Asians: lower,P=0.040). East and South Asians were more insulin resistant than Western Europeans at V1. From V1 to V2, the increase in insulin resistance was similar across the ethnic groups, but the increase in β-cell function was significantly lower for the East and South Asians compared with Western Europeans. GDM women compared with non-GDM women were more insulin resistant at V1; from V1 to V2, their β-cell function increased significantly less and the percentage increase in β-cell function did not match the change in insulin resistance.

Conclusion

Pregnant women from East Asia and South Asia were more insulin resistant and showed poorer HOMA-β-cell function than Western Europeans.
Sphingosine 1-phosphate and human ether-a′-go-go-related gene potassium channels modulate migration in human anaplastic thyroid cancer cells
Authors: Asghar Muhammad Yasir , Viitanen Tero , Kemppainen Kati , Törnquist Kid
Published: August 2012

Anaplastic thyroid cancer (ATC) is the most aggressive form of human thyroid cancer, lacking any effective treatment. Sphingosine 1-phosphate (S1P) receptors and human ether-a′-go-go-related gene (HERG (KCNH2)) potassium channels are important modulators of cell migration. In this study, we have shown that the S1P1–3 receptors are expressed in C643 and THJ-16T human ATC cell lines, both at mRNA and protein level. S1P inhibited migration of these cells and of follicular FTC-133 thyroid cancer cells. Using the S1P1,3 inhibitor VPC-23019, the S1P2 inhibitor JTE-013, and the S1P2 receptor siRNA, we showed that the effect was mediated through S1P2. Treatment of the cells with the Rho inhibitor C3 transferase abolished the effect of S1P on migration. S1P attenuated Rac activity, and inhibiting Rac decreased migration. Sphingosine kinase inhibitor enhanced basal migration of cells, and addition of exogenous S1P inhibited migration. C643 cells expressed a nonconducting HERG protein, and S1P decreased HERG protein expression. The HERG blocker E-4031 decreased migration. Interestingly, downregulating HERG protein with siRNA decreased the basal migration. In experiments using HEK cells overexpressing HERG, we showed that S1P decreased channel protein expression and current and that S1P attenuated migration of the cells. We conclude that S1P attenuates migration of C643 ATC cells by activating S1P2 and the Rho pathway. The attenuated migration is also, in part, dependent on a S1P-induced decrease of HERG protein.
Mortality and Clinical Outcomes in HIV-Infected Children on Antiretroviral Therapy in Malawi, Lesotho, and Swaziland
Authors: Kabue Mark M. , Buck W. Chris , Wanless Sebastian R. , Cox Carrie M. , McCollum Eric D. , Caviness A. Chantal , Ahmed Saeed , Kim Maria H. , Thahane Lineo , Devlin Andrew , Kochelani Duncan , Kazembe Peter N. , Calles Nancy R. , Mizwa Michael B. , Schutze Gordon E. , Kline Mark W.
Published: August 2012

OBJECTIVE:

To determine mortality and immune status improvement in HIV-infected pediatric patients on antiretroviral treatment (ART) in Malawi, Lesotho, and Swaziland.

METHODS:

We conducted a retrospective cohort study of patients aged <12 years at ART initiation at 3 sites in sub-Saharan Africa between 2004 and 2009. Twelve-month and overall mortality were estimated, and factors associated with mortality and immune status improvement were evaluated.

RESULTS:

Included in the study were 2306 patients with an average follow-up time on ART of 2.3 years (interquartile range 1.5–3.1 years). One hundred four patients (4.5%) died, 9.0% were lost to follow-up, and 1.3% discontinued ART. Of the 104 deaths, 77.9% occurred in the first year of treatment with a 12-month mortality rate of 3.5%. The overall mortality rate was 2.25 deaths/100 person-years (95% confidence interval [CI] 1.84–2.71). Increased 12-month mortality was associated with younger age; <6 months (hazard ratio [HR] = 8.11, CI 4.51–14.58), 6 to <12 months (HR = 3.43, CI 1.96–6.02), and 12 to <36 months (HR = 1.92, CI 1.16–3.19), and World Health Organization stage IV (HR = 4.35, CI 2.19–8.67). Immune status improvement at 12 months was less likely in patients with advanced disease and age <12 months.

CONCLUSIONS:

Despite challenges associated with pediatric ART in developing countries, low mortality and good treatment outcomes can be achieved. However, outcomes are worse in younger patients and those with advanced disease at the time of ART initiation, highlighting the importance of early diagnosis and treatment.
Efficacy of Fat-Soluble Vitamin Supplementation in Infants With Biliary Atresia
Authors: Shneider Benjamin L. , Magee John C. , Bezerra Jorge A. , Haber Barbara , Karpen Saul J. , Raghunathan Trivellore , Rosenthal Philip , Schwarz Kathleen , Suchy Frederick J. , Kerkar Nanda , Turmelle Yumirle , Whitington Peter F. , Robuck Patricia R. , Sokol Ronald J.
Published: August 2012

OBJECTIVE:

Cholestasis predisposes to fat-soluble vitamin (FSV) deficiencies. A liquid multiple FSV preparation made with tocopheryl polyethylene glycol-1000 succinate (TPGS) is frequently used in infants with biliary atresia (BA) because of ease of administration and presumed efficacy. In this prospective multicenter study, we assessed the prevalence of FSV deficiency in infants with BA who received this FSV/TPGS preparation.

METHODS:

Infants received FSV/TPGS coadministered with additional vitamin K as routine clinical care in a randomized double-blinded, placebo-controlled trial of corticosteroid therapy after hepatoportoenterostomy (HPE) for BA (identifier NCT 00294684). Levels of FSV, retinol binding protein, total serum lipids, and total bilirubin (TB) were measured 1, 3, and 6 months after HPE.

RESULTS:

Ninety-two infants with BA were enrolled in this study. Biochemical evidence of FSV insufficiency was common at all time points for vitamin A (29%–36% of patients), vitamin D (21%–37%), vitamin K (10%–22%), and vitamin E (16%–18%). Vitamin levels were inversely correlated with serum TB levels. Biochemical FSV insufficiency was much more common (15%–100% for the different vitamins) in infants whose TB was ≥2 mg/dL. At 3 and 6 months post HPE, only 3 of 24 and 0 of 23 infants, respectively, with TB >2 mg/dL were sufficient in all FSV.

CONCLUSIONS:

Biochemical FSV insufficiency is commonly observed in infants with BA and persistent cholestasis despite administration of a TPGS containing liquid multiple FSV preparation. Individual vitamin supplementation and careful monitoring are warranted in infants with BA, especially those with TB >2 mg/dL.
Preterm Birth and Body Composition at Term Equivalent Age: A Systematic Review and Meta-analysis
Authors: Johnson Mark J. , Wootton Stephen A. , Leaf Alison A. , Jackson Alan A.
Published: August 2012

BACKGROUND AND OBJECTIVE:

Infants born preterm are significantly lighter and shorter on reaching term equivalent age (TEA) than are those born at term, but the relation with body composition is less clear. We conducted a systematic review to assess the body composition at TEA of infants born preterm.

METHODS:

The databases MEDLINE, Embase, CINAHL, HMIC, “Web of Science,” and “CSA Conference Papers Index” were searched between 1947 and June 2011, with selective citation and reference searching. Included studies had to have directly compared measures of body composition at TEA in preterm infants and infants born full-term. Data on body composition, anthropometry, and birth details were extracted from each article.

RESULTS:

Eight studies (733 infants) fulfilled the inclusion criteria. Mean gestational age and weight at birth were 30.0 weeks and 1.18 kg in the preterm group and 39.6 weeks and 3.41 kg in the term group, respectively. Meta-analysis showed that the preterm infants had a greater percentage total body fat at TEA than those born full-term (mean difference, 3%; P = .03), less fat mass (mean difference, 50 g; P = .03), and much less fat-free mass (mean difference, 460 g; P < .0001).

CONCLUSIONS:

The body composition at TEA of infants born preterm is different than that of infants born at term. Preterm infants have less lean tissue but more similar fat mass. There is a need to determine whether improved nutritional management can enhance lean tissue acquisition, which indicates a need for measures of body composition in addition to routine anthropometry.
Effects of CPOE on Provider Cognitive Workload: A Randomized Crossover Trial
Authors: Avansino Jeffrey , Leu Michael G.
Published: August 2012

OBJECTIVE:

To evaluate whether systematically developed clinical decision supports provide usability benefit or decreased cognitive workload with their use.

METHODS:

Seven surgeons at a pediatric hospital at different levels of training (3 residents, 3 fellows, and 1 attending) were randomized to use either a historical control (ad hoc developed order set) or a systematically developed order set for postoperative management of appendicitis in children. After a washout period, they were crossed over to the other order set. Participants were videorecorded and completed postsurveys, including the System Usability Scale and the National Aeronautic and Space Administration–Task Load Index.

RESULTS:

Participants unanimously preferred using systematically developed order sets. These order sets resulted in higher usability scores (75 ± 10 vs 60 ± 19; P < .05) and lower cognitive workload scores (37.7 ± 15 vs 52.2 ± 12; P < .05), with comparable amounts of time spent, mouse clicks, and free text entry. Orders generated were more likely to conform to established clinical guidelines.

CONCLUSIONS:

Systematically designed order sets provide a reduction in cognitive workload and order variation in the context of improved system usability and improved guideline adherence. The systematically designed order set did not improve time spent, reduce mouse clicks, or reduce free text entry.
Persistent Snoring in Preschool Children: Predictors and Behavioral and Developmental Correlates
Authors: Beebe Dean W. , Rausch Joseph , Byars Kelly C. , Lanphear Bruce , Yolton Kimberly
Published: August 2012

OBJECTIVE:

To clarify whether persistent snoring in 2- to 3-year-olds is associated with behavioral and cognitive development, and to identify predictors of transient and persistent snoring.

METHODS:

Two hundred forty-nine mother/child pairs participated in a prospective birth cohort study. Based upon parental report of loud snoring ≥2 times weekly at 2 and 3 years of age, children were designated as nonsnorers, transient snorers (snored at 2 or 3 years of age, but not both), or persistent snorers (snored at both ages). We compared groups by using validated measures of behavioral and cognitive functioning. Potential predictors of snoring included child race and gender, socioeconomic status (parent education and income), birth weight, prenatal tobacco exposure (maternal serum cotinine), childhood tobacco exposure (serum cotinine), history and duration of breast milk feeding, and body mass relative to norms.

RESULTS:

In multivariable analyses, persistent snorers had significantly higher reported overall behavior problems, particularly hyperactivity, depression, and inattention. Nonsnorers had significantly stronger cognitive development than transient and persistent snorers in unadjusted analyses, but not after demographic adjustment. The strongest predictors of the presence and persistence of snoring were lower socioeconomic status and the absence or shorter duration of breast milk feeding. Secondary analyses suggested that race may modify the association of childhood tobacco smoke exposure and snoring.

CONCLUSIONS:

Persistent, loud snoring was associated with higher rates of problem behaviors. These results support routine screening and tracking of snoring, especially in children from low socioeconomic backgrounds; referral for follow-up care of persistent snoring in young children; and encouragement and facilitation of infant breastfeeding.
Pediatric-Specific Antimicrobial Susceptibility Data and Empiric Antibiotic Selection
Authors: Boggan Joel C. , Navar-Boggan Ann Marie , Jhaveri Ravi
Published: August 2012

OBJECTIVE:

Duke University Health System (DUHS) generates annual antibiograms combining adult and pediatric data. We hypothesized significant susceptibility differences exist for pediatric isolates and that distributing these results would alter antibiotic choices.

METHODS:

Susceptibility rates for Escherichia coli isolates from patients aged ≤12 years between July 2009 and September 2010 were compared with the 2009 DUHS antibiogram. Pediatric attending and resident physicians answered case-based vignettes about children aged 3 months and 12 years with urinary tract infections. Each vignette contained 3 identical scenarios with no antibiogram, the 2009 DUHS antibiogram, and a pediatric-specific antibiogram provided. Effective antibiotics exhibited >80% in vitro susceptibility. Frequency of antibiotic selection was analyzed by using descriptive statistics.

RESULTS:

Three hundred seventy-five pediatric isolates were identified. Pediatric isolates were more resistant to ampicillin and trimethoprim-sulfamethoxazole (TMP-SMX) and less resistant to amoxicillin-clavulanate and ciprofloxacin (P < .0005 for all). Seventy-five resident and attending physicians completed surveys. In infant vignettes, physicians selected amoxicillin-clavulanate (P < .05) and nitrofurantoin (P < .01) more often and TMP-SMX (P < .01) less often with pediatric-specific data. Effective antibiotic choices increased from 68.6% to 82.2% (P = .06) to 92.5% (P < .01) across scenarios. In adolescent vignettes, providers reduced TMP-SMX use from 66.2% to 42.6% to 19.0% (P < .01 for both). Effective antibiotic choices increased from 32.4% to 57.4% to 79.4% (P < .01 and P = .01).

CONCLUSIONS:

Pediatric E. coli isolates differ significantly in antimicrobial susceptibility at our institution, particularly to frequently administered oral antibiotics. Knowledge of pediatric-specific data altered empirical antibiotic choices in case vignettes. Care of pediatric patients could be improved with use of a pediatric-specific antibiogram.
Proton-pump inhibitor therapy and small bowel bacterial contamination
Authors: Hamvas József
Published: August 2012

There are several causes of small bowel contamination. The effects of the long-term proton pump inhibitor treatment on the development of bowel symptoms and/or small intestinal bacterial overgrowth have been highlighted only in the past decade. The main diagnostic method is the hydrogen breath test that gives quantitative results with a simple, non-invasive procedure. There is a limited number of publications in the literature about the effects of proton pump inhibitor drugs on bowel bacterial milieau. Our results based on the investigations of two medical centres in Budapest show consistency with international data: the positive hydrogen breath test was present in 21% of the population using long-term proton pump inhibitors. In uncomplicated cases, symptom-free condition could be reached with probiotics, whereas in long lasting, chronic small intestinal bacterial overgrowth, antibiotic treatment should be considered. Rifaximin, a non-absorbable antibiotic showed high efficacy in the treatment of small intestinal bacterial overgrowth, with fewer side effects compared to systemic antibiotics. Orv. Hetil., 2012, 153, 1287–1293.
Removal of Fractured Dental Implant Screw Using a New Technique: A Case Report
Authors: Walia Manpreet S. , Arora Saryu , Luthra Reena , Walia Prabhjot Kaur
Published: August 2012

Implant restorations can fail biologically or mechanically. Biological factors include unsuccessful osseointegration or presence of peri-implantitis. Mechanical failures include crown fracture, framework fracture, screw loosening, and screw fracture. Fracture of the implant abutment can be a serious problem as the fragment remaining inside the implant may prevent the implant from functioning efficiently. The procedure used for removal of the fractured screw portion is described in this clinical report.
Mandibular Implant-Supported Overdenture: An In Vitro Comparison of Ball, Bar, and Magnetic Attachments
Authors: Manju V. , Sreelal T.
Published: August 2012

In an implant-supported overdenture, the optimal stress distribution on the implants and least denture displacement is desirable. This study compares the load transfer characteristics to the implant and the movement of overdenture among 3 different types of attachments (ball-ring, bar-clip, and magnetic). Stress on the implant surface was measured using the strain-gauge technique and denture displacement by dial gauge. The ball/O-ring produces the optimal stress on the implant body and promotes denture stability.
Chemical composition and fermentation characteristics of elephant grass silage with biodiesel industry co-products
Authors: Cleef Eric Haydt Castello Branco van , Silva Filho José Cleto da , Neiva Júnior Arnaldo Prata , Patiño Pardo René Maurício , Rêgo Aníbal Coutinho do , Gonçalves Josemir de Souza
Published: August 2012

The objective of this research was to evaluate the effect of three concentrations (3, 6, and 9%) of forage turnip (Raphanus sativus) and physic nut (Jatropha curcas) cakes on dry matter, crude protein, ether extract, neutral detergent fiber, acid detergent fiber, lignin, acid detergent insoluble nitrogen neutral detergent insoluble nitrogen contents, in vitro dry matter digestibility, pH values and concentrations of N-NH3 in elephant grass silages. It was used an entirely randomized design in factorial arrangement [(2×3)+1]. Experimental PVC silos were used and ensiled material was kept for 62 days. The addition of cakes increased the dry matter contents (P<0.05). The fibrous fractions were reduced (P<0.05) with the inclusion of cakes during the grass ensilage and the CP contents increased (P<0.05). The forage turnip cake provided the same pH and N-NH3 values in ideal levels and the physic nut, added to 9%, increased those values (P<0.05). IVDMD was reduced (P<0.05) when the cakes were added. These co-products can be used in small amounts for elephant grass ensilage in order to provide improvement in chemical and fermentation characteristics of the silages. Nevertheless, physic nut cake shows limitations for its use in animal feeding due to the presence of toxic compounds, making necessary studies for their identification and elimination.
Health related quality of life of patients undergoing oral anticoagulation therapy
Authors: Corbi Inaiara Scalçone Almeida , Dantas Rosana Aparecida Spadoti , Pelegrino Flávia Martinelli , Carvalho Ariana Rodrigues da Silva
Published: August 2012

This is a descriptive cross-sectional study, which aimed to analyze the health related quality of life (HRQoL) and its relationship with gender, age, duration and indication for the use of oral anticoagulants. A total of 178 patients were interviewed and the HRQoL was assessed through eight domains of the SF-36. The descriptive statistics used were, the Student's t, ANOVA and Tukey's tests for the comparison of the means between the groups. The indication for use was predominantly the metallic prosthetic heart valve (50%) with warfarin the most widely prescribed anticoagulant (83.3%). The means of the domains of the SF-36 ranged from 82 (Social aspects) to 54.8 (Physical aspects). Women, elderly, patients diagnosed with atrial fibrillation and with less than one year of medication use, presented a worse HRQoL evaluation. The results obtained can guide nursing actions, in that they indicate possible associations between the HRQoL and the sociodemographic and clinical variables of the patients.
Nutritional characteristics and in vitro digestibility of silages from different corn cultivars harvested at two cutting heights
Authors: Caetano H. , Oliveira M.D.S. , Freitas Júnior J.E. , Rêgo A.C. , Carvalho M.V. , Rennó F.P.
Published: August 2012

The objective of this study was to evaluate the nutritional traits and in vitro digestibility of silages from different corn cultivars harvested at two cutting heights. It was evaluated 11 cultivars (Dina 766, Dina 657, Dina 1000, P 3021, P 3041, C 805, C 333, AG 5011, FO 01, Dina co 9621 and BR 205) harvest 5 cm above ground (low) and 5 cm below the intersection of the first ear (high). It was used a random block design (three blocks), arranged in a 11 × 2 factorial scheme. Silages from plants harvested at high cutting height presented average content of dry matter significantly superior to silages from plants harvested at low height. Cultivars FO 01, AG 5011, Dina co 9621 and Dina 766 presented greater content of crude protein than cultivars C 805, P 3041 and P 3021, which presented the lowest contents of this nutrient. The raise in the cut height increased in vitro dry matter true digestibility coefficients and in vitro dry matter digestibility of silage evaluated. The increase in cut height improved nutritive value of silages by decreasing concentrations of fibrous fractions and increasing in vitro dry matter digestibility.
New specific metal-silica biocomposites for medical implants
Authors: Donesz-Sikorska Anna , Krzak-Roś Justyna , Kochanowska Iwona Ewa , Będziński Romuald , Kaleta Jerzy
Published: August 2012

All metallic biomaterials contain elements which may cause metallosis or corrosion, and their surfaces may not promote colonization by cells of the surrounding tissue. In this paper, the authors describe new materials for coating on a commercially available alloy that act as bio-functional as well as a better protective coating for medical implants. The authors have chosen the stainless steel 316L for deposition of silica doped thin films prepared by sol-gel method. Two different silica precursors have been used: tetramethylorthosilicate and tetraethylorthosilicate and two others with halides substituents: 3-chloropropyl-trimethoxysilane and fluorotriethoxy-silane. Ethanol was used as solvent and hydrochloric acid as catalyst. Cleaned metallic substrate were dip-coated by the sols, then dried at room temperature in air and stabilized at a temperature of 50°C, 300°C, and 500°C. The materials were variously examined: structurally (scanning electron microscopy, roughness measurements), physic-chemically (attenuated total reflectance-fourier transform infrared spectroscopy), and mechanically (four-point bending test). Tests results indicate that the sol-gel produced materials exhibit continuous coatings that can improve the surfaces of metallic biomaterials.
A novel material used in automotive industry: compacted graphite iron
Authors: Behera Ajit , Mishra S. C.
Published: August 2012

In recent decades, materials have been a key to increase the performance of automotive parts which leads to development of new materials. The main objective is to achieve increase in quantity and quality of automotive parts produced with optimum performance during their life cycle. Cast iron has remained a competitive material due, in part, to its low production cost. In fact, among the cast iron group, one of the alternatives is lightweight alloys, that is, compacted graphite iron (CGI). Nowadays, it is accepted that CGI can effectively reduce the total weight of an automobile by virtue of its high strength- when compared to other cast irons and aluminum alloys. The paper presents a comparative view of CGI with gray cast iron and ductile iron. Surface morphology has been studied by scanning electron microscopy. Tensile strength and other properties have been calculated by stress-strain curves. Hardness has been measured by Brinell hardness testing methods. Several metallurgical variables need to be strictly controlled in order to achieve consistent CGI properties in a production line at reasonable costs for the automotive industry with at least 75% higher tensile strength, 45% higher stiffness and approximately double the fatigue strength of conventional grey cast iron.
Foam-like materials produced from milk and sodium montmorillonite clay using a freeze-drying process
Authors: Wang Yuxin , Schiraldi David A.
Published: August 2012

Fresh milk and sodium montmorillonite clay can be used to prepare foam-like materials via an environmentally sustainable freeze-drying process. The enzyme transglutaminase (Tgase) was demonstrated to be an effective cross-linker; treatment of milk with Tgase contributed to the formation of a gel network. The mechanical properties of milk/clay composites after freeze-drying were greatly improved (e.g. compressive moduli increasing from 1·4 to 13 MPa). Milk beyond its expiration date was also used in this research, demonstrating that dairy products unsuitable for human consumption can be turned into useful engineering materials.
Development of Conformationally Restricted Analogues of Bradykinin and Somatostatin Using Constrained Amino Acids and Different Types of Cyclization
Authors: Reissmann Siegmund , Imhof Diana
Published: August 2012

The structure-based design of peptide drugs requires the knowledge of the bioactive conformation. Studies on this receptor-bound 3D structure require linear or cyclic analogues with strongly reduced flexibility, but high biological activity, since only analogues with retained potency have preserved the bioactive conformation. Constrained amino acids containing double bonds or bulky substituents at the Nα-, Cα- and Cβ-atom as well as at the aromatic ring atom were successfully applied to obtain potent and stable analogues of bradykinin and somatostatin, which due to their restricted conformation were suitable objects for conformational studies. Besides the generation of constrained cyclic analogues with improved biological and pharmacological properties, cyclic peptides were used as convenient models for the study of turn formations. Cyclization of the linear peptide bradykinin was performed by linking the N-terminus and the C-terminus, and in both bradykinin and somatostatin by cyclization using the amino acid side chains and by backbone cyclization. The later requires the introduction of Nα-functionalised amino acids for ring closure which can be performed either through incorporation of Nβ-functionalised amino acids or dipeptide building units. Conformational analysis of a cyclic bradykinin analogue by means of NMR-studies together with molecular dynamics simulation led to a quasicyclic 3D structure with two turns and together with other 3D structures provided a pharmacophore model of bradykinin antagonists.
Haemoglobinopathy in Pregnancy: Diagnosis and Treatment
Authors: Krafft A. , Breymann C.
Published: August 2012

Haemoglobinopathies differ in geographic prevalence but together are amongst the most common genetic disorders worldwide. Despite huge diagnostic progress, therapeutic options remain limited, with many treatments still at the experimental stage, no more so than in pregnancy: not only does the presence of a fetus subject treatments to greater limitations, but also any worsening of the anaemia as pregnancy progresses results in higher fetomaternal morbidity and mortality. Anaemia weakens the response to peripartum blood loss, with the risk of postpartum complications. Until recently the standard conventional therapy for severe anaemia was (repeated) blood transfusion, with its well-known risks. Recombinant human erythropoietin (rhEPO) can induce fetal haemoglobin and is a safer, if less immediately effective, alternative for the correction of anaemia in pregnant patients with haemoglobinopathy.
The Potential of Tetrandrine Against Gliomas
Authors: Chen Yun , Tseng Sheng-Hong
Published: August 2012

Patients with malignant gliomas have poor prognoses, and the majority of the patients have local tumor recurrence after various treatments including surgery, radiotherapy, and chemotherapy. Thus it is mandatory to develop better therapies for treatment of these malignant brain tumors. Tetrandrine, a bisbenzylisoquinoline alkaloid, has antitumor effects against some cancers. Tetrandrine affects the cell cycle, production of reactive oxygen species, mitogen-activated protein kinase activity, and reverses multidrug resistance in various cancer cells. Since tetrandrine is a highly lipid-soluble and hydrophobic molecule with a low molecular weight, it may cross the blood brain barrier; thus, it could be used for the treatment of gliomas. Tetrandrine inhibits the large-conductance, calcium-activated potassium (BK) channels and the expression of BK channel has a positive correlation with tumor malignancy grade in human gliomas. Furthermore, tetrandrine also exerts cytotoxic effects, and induces apoptosis and radiosensitization in glioma cells by elimination of radiation-induced cell cycle perturbation. It also has anti-angiogenesis effects in gliomas, and exerts an antitumor effect on subcutaneous and intracerebral gliomas. Tetrandrine is a radiosensitizer and also a multidrug resistance reversing agent. Tetrandrine can probably be combined with radiotherapy or other chemotherapeutic agents to treat gliomas. Nonetheless, it is important to determine the balance between the safety and efficacy of tetrandrine in patients with malignant gliomas before any clinical application.
FK506 Binding Proteins as Targets in Anticancer Therapy
Authors: Romano Simona , Di Pace AnnaLaura , Sorrentino Antonio , Bisogni Rita , Sivero Luigi , Fiammetta Romano Maria
Published: August 2012

FK506 binding proteins (FKBPs) are the intracellular ligands of FK506 and rapamycin, two natural compounds with powerful and clinically efficient immunosuppressive activity. In recent decades, a relevant role for immunosuppressants as anticancer agents has emerged. Especially, rapamycin and its derivatives are used, with successful results, across a variety of tumors. Of note, rapamycin and FK506 bind to FKBP12, and the resulting complexes interfere with distinct intracellular signaling pathways driven, respectively, by the mammalian target of rapamycin and calcineurin phosphatase. These pathways are related to T-cell activation and growth. Hyperactivation of the mammalian target of rapamycin (mTOR), particularly in cancers that have lost the tumor suppressor gene PTEN, plays an important pathogenetic role in tumor transformation and growth. The signaling pathway involving calcineurin and nuclear factors of activated T-lymphocytes is also involved in the pathogenesis of different cancer types and in tumor metastasis, providing a rationale for use of FK506 in anticancer therapy. Recent studies have focused on FKBPs in apoptosis regulation: Targeting of FKBP12 promotes apoptosis in chronic lymphocytic leukemia, FKBP38 knockdown sensitizes hepatoma cells to apoptosis, and FKBP51 silencing overcomes resistance to apoptosis in acute lymphoblastic leukemia, prostate cancer, melanoma, and glioma. Interestingly, derivatives of FK506 that have the same FKBP12-binding properties as FK506 but lack functional immunosuppressant activity, exert the same apoptotic effect as FK506 in chronic lymphocytic leukemia. These findings suggest that a direct FKBP inhibition represents a further mechanism of immunosuppressants anticancer activity. In this review, we focus on the role of FKBP members in apoptosis control and summarize the data on the antitumor effect of selective targeting of FKBP.
Topoisomerase I Inhibitors in the Treatment of Primary CNS Malignancies: An Update on Recent Trends
Authors: P. Sasine Joshua , Savaraj Niramol , G. Feun Lynn
Published: August 2012

High grade primary CNS gliomas hold some of the worst prognoses of any malignancy, with the vast majority of patients dying within two years of diagnosis, even with aggressive modern treatments. Surgical resection and radiotherapy are cornerstones of treatment when possible. In spite of many years of research, only recently has management with chemotherapy been able to prolong survival in patients with high grade gliomas, albeit only modestly at best. Topoisomerase I (TOP1) inhibitors target an enzyme critical for DNA replication and cell-cycle progression; they cross the blood-brain barrier and have antitumor activity against glioblastoma cells in vitro. The most frequently associated toxicities are neutropenia and diarrhea, but are often manageable. The two most used agents are irinotecan and topotecan. Due to enhanced cytochrome CY3A4/5 enzyme activity, irinotecan dose must be adjusted with concomitant enzyme- inducing antiepileptic drug usage; the data is less clear regarding the effects on topotecan. Clinical trials in patients with recurrent malignant glioma have evaluated TOP1 inhibitors as monotherapy and in combination with other agents. There is evidence for using topotecan with radiotherapy. Irinotecan has limited efficacy as monotherapy, but shows promise in combination with other agents, particularly temozolomide and bevacizumab. Newer generation TOP1 inhibitors are currently being evaluated in phase I trials. TOP1 inhibitors show promising activity in patients with primary CNS malignancies and warrant further study.
Targeted Therapies in Metastatic Melanoma: Toward a Clinical Breakthrough?
Authors: Julia Fanny , Thomas Luc , Dumontet Charles , Dalle Stephane
Published: August 2012

Metastatic melanoma is a very aggressive cancer. Dacarbazine has been considered as the standard therapy for decades. Due to a better understanding of melanoma cells signalling and immunological response, new targeted therapies are now proposed. The efficency of these new drugs needs to be confirmed by on larger clinical trials. Ipilimumab (anti-CTLA4 monoclonal antibody) and V600-E- B-raf inhibitor have shown encouraging results, while c-KIT and MEK inhibitors are currently under evaluation. These recently published data shed the light on melanoma management. We review here the latest development of these molecules and the current perspectives in the treatment of metastatic melanoma.
Prospective study of dentoskeletal changes in Class II division malocclusion treatment with twin force bite corrector
Authors: Guimarães Carlos Henrique , Henriques José Fernando Castanha , Janson Guilherme , de Almeida Marcio Rodrigues , Araki Janine , Cançado Rodrigo Hermont , Castro Renata , Nanda Ravindra
Published: August 2012

Objective:

To evaluate the dentoskeletal changes of Class II malocclusion treatment with the Twin Force Bite Corrector (TFBC).

Materials and Methods:

The sample comprised 86 lateral cephalograms obtained from 43 subjects with Class II division 1 malocclusion; the subjects were divided into two groups. The experimental group comprised 23 patients with a mean initial age of 12.11 years who were treated with the TFBC for a mean period of 2.19 years. The control group included 40 lateral cephalograms from 20 Class II nontreated patients, with an initial mean age of 12.55 years and a mean observation period of 2.19 years. The lateral cephalograms were evaluated before and after orthodontic treatment in group 1 and in the beginning and end of the observation period in group 2. t-Tests were used to compare the initial and final cephalometric characteristics of the groups as well as the amount of change.

Results:

The experimental group presented greater maxillary growth restriction and mandibular retrusion than the control group, as well as greater maxillomandibular relationship improvement and greater labial tipping of the mandibular incisors. The results also showed a greater decrease in overbite and overjet in the experimental group, and there were no statistically significant differences in the craniofacial growth pattern between groups.

Conclusions:

The TFBC promotes restriction of anterior maxillary displacement without significant changes in mandibular length and position and improvement of maxillomandibular relationship without changes in facial growth and significant buccal tipping of mandibular incisors. Class II correction with the TFBC occurred primarily as a result of dentoalveolar changes.
Therapeutic Potential of a Monoclonal Antibody Blocking the Wnt Pathway in Diabetic Retinopathy
Authors: Lee Kyungwon , Hu Yang , Ding Lexi , Chen Ying , Takahashi Yusuke , Mott Robert , Ma Jian-xing
Published: August 2012

Dysregulation of Wnt/β-catenin signaling contributes to the development of diabetic retinopathy by inducing retinal inflammation, vascular leakage, and neovascularization. Here, we evaluated the inhibitory effect of a monoclonal antibody (Mab) specific for the E1E2 domain of Wnt coreceptor low-density lipoprotein receptor–related protein 6, Mab2F1, on canonical Wnt signaling and its therapeutic potential for diabetic retinopathy. Mab2F1 displayed robust inhibition on Wnt signaling with a half-maximal inhibitory concentration (IC50) of 20 μg/mL in retinal pigment epithelial cells. In addition, Mab2F1 also attenuated the accumulation of β-catenin and overexpression of vascular endothelial growth factor, intercellular adhesion molecule-1, and tumor necrosis factor-α induced by high-glucose medium in retinal endothelial cells. In vivo, an intravitreal injection of Mab2F1 significantly reduced retinal vascular leakage and decreased preretinal vascular cells in oxygen-induced retinopathy (OIR) rats, demonstrating its inhibitory effects on ischemia-induced retinal neovascularization. Moreover, Mab2F1 blocked the overexpression of the inflammatory/angiogenic factors, attenuated leukostasis, and reduced retinal vascular leakage in both early and late stages of streptozotocin-induced diabetes. In conclusion, Mab2F1 inhibits canonical Wnt signaling, vascular leakage, and inflammation in the retina of diabetic retinopathy models, suggesting its potential to be used as a therapeutic agent in combination with other antiangiogenic compounds.
Mitochondrial DNA Coding and Control Region Variants as Genetic Risk Factors for Type 2 Diabetes
Authors: Liou Chia-Wei , Chen Jin-Bor , Tiao Mao-Meng , Weng Shao-Wen , Huang Tiao-Lai , Chuang Jiin-Haur , Chen Shang-Der , Chuang Yao-Chung , Lee Wen-Chin , Lin Tsu-Kung , Wang Pei-Wen
Published: August 2012

Both the coding and control regions of mitochondrial DNA (mtDNA) play roles in the generation of diabetes; however, no studies have thoroughly reported on the combined diabetogenic effects of variants in the two regions. We determined the mitochondrial haplogroup and the mtDNA sequence of the control region in 859 subjects with diabetes and 1,151 normoglycemic control subjects. Full-length mtDNA sequences were conducted in 40 subjects harboring specific diabetes-related haplogroups. Multivariate logistic regression analysis with adjustment for age, sex, and BMI revealed that subjects harboring the mitochondrial haplogroup B4 have significant association with diabetes (DM) (odds ratio [OR], 1.54 [95% CI 1.18–2.02]; P < 0.001), whereas subjects harboring D4 have borderline resistance against DM generation (0.68 [0.49–0.94]; P = 0.02). Upon further study, we identified an mtDNA composite group susceptible to DM generation consisting of a 10398A allele at the coding region and a polycytosine variant at nucleotide pair 16184–16193 of the control region, as well as a resistant group consisting of C5178A, A10398G, and T152C variants. The OR for susceptible group is 1.31 (95% CI 1.04–1.67; P = 0.024) and for the resistant group is 0.48 (0.31–0.75; P = 0.001). Our study found that mtDNA variants in the coding and control regions can have combined effects influencing diabetes generation.