bluuebunny/crossref_metadata_2025_split huggingface dataset:
One-Step Surgery With Multipotent Stem Cells for the Treatment of Large Full-Thickness Chondral Defects of the Knee
Authors: Gobbi Alberto , Karnatzikos Georgios , Sankineani Sukesh Rao 
Published: January 2014

Background: Chondral lesions in athletically active patients cause considerable morbidity, and treatment with existing cell-based therapies can be challenging. Bone marrow has been shown as a possible source of multipotent stem cells (MSCs) with chondrogenic potential and is easy to harvest during the same surgical procedure. Purpose: To investigate the clinical outcome in a group of active patients with large full-thickness chondral defects of the knee treated with 1-step surgery using bone marrow–derived MSCs and a second-generation matrix. Study Design: Case series; Level of evidence, 4. Methods: From January 2007 to February 2010, 25 patients (average age, 46.5 years) with symptomatic large chondral defects of the knee (International Cartilage Repair Society grade 4) who underwent cartilage transplantation with MSCs and a collagen type I/III matrix were followed up for a minimum of 3 years. The average lesion size was 8.3 cm2. Coexisting injuries were treated during the same surgical procedure in 18 patients. All patients underwent a standard postoperative rehabilitation program. Preoperative and postoperative evaluations at 1-year, 2-year, and final follow-up included radiographs, magnetic resonance imaging (MRI), and visual analog scale (VAS) for pain, International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm, Marx, and Tegner scores. Seven patients underwent second-look arthroscopic surgery, with 4 consenting to a tissue biopsy. Results: No patients were lost at final follow-up. The average preoperative values for the evaluated scores were significantly improved at final follow-up ( P < .001): VAS, 5.4 ± 0.37 to 0.48 ± 0.19; IKDC subjective, 37.92 ± 4.52 to 81.73 ± 2.42; KOOS pain, 61.04 ± 3.95 to 93.32 ± 1.92; KOOS symptoms, 55.64 ± 3.23 to 89.32 ± 2.32; KOOS activities of daily living, 63.96 ± 4.48 to 91.20 ± 2.74; KOOS sports, 34.20 ± 5.04 to 80.00 ± 3.92; KOOS quality of life, 32.20 ± 4.43 to 83.04 ± 3.37; Lysholm, 46.36 ± 2.25 to 86.52 ± 2.73; Marx, 3.00 ± 0.79 to 9.04 ± 0.79; and Tegner, 2.12 ± 0.32 to 5.64 ± 0.26. Patients younger than 45 years of age and those with smaller or single lesions showed better outcomes. The MRI scans showed good stability of the implant and complete filling of the defect in 80% of patients, and hyaline-like cartilage was found in the histological analysis of the biopsied tissue. No adverse reactions or postoperative complications were noted. Conclusion: The treatment of large chondral defects with MSCs is an effective procedure and can be performed routinely in clinical practice. Moreover, it can be achieved with 1-step surgery, avoiding a previous surgical procedure to harvest cartilage and subsequent chondrocyte cultivation.
Correlates of syphilis seropositivity and risk for syphilis-associated adverse pregnancy outcomes among women attending antenatal care clinics in the Democratic Republic of Congo
Authors: Taylor Melanie M , Ebrahim Shahul , Abiola Nadine , Kinkodi Didine Kaba , Mpingulu Minlangu , Kabuayi Jean Pierre , Ekofo Felly , Newman Daniel R , Peterman Thomas A , Kamb Mary L , Sidibe Kassim 
Published: January 2014

Summary Screening and treatment for syphilis among pregnant women is the primary means of prevention of congenital syphilis. Sentinel surveillance for syphilis can inform these prevention efforts. We reviewed antenatal syphilis screening results to assess trends and to identify correlates of seropositivity among women attending antenatal care clinics in the Democratic Republic of Congo during 2011. Syphilis seropositivity among the 17,669 women attending the antenatal care clinics during 2011 was 4.2% (range 0.4%-16.9%). Syphilis seropositivity was significantly higher among women attending rural clinics (5.0%) as compared to urban clinics (3.0%) and those tested in antenatal care clinics in the provinces of Equateur (7.6%) and Orientale (7.7%) as compared to other provinces ( p < 0.001). Based on the antenatal care syphilis seroprevalence and national pregnancy estimates, we estimate that approximately 128,591 pregnant women countrywide would have tested seropositive for syphilis during 2011. Over 85,000 adverse pregnancy outcomes would have resulted from these maternal infections, assuming prenatal syphilis diagnosis and treatment were not available. The prevalence of syphilis was highest in rural areas, but exceeded 1% in every area, indicating a need to assure screening and treatment throughout Democratic Republic of Congo. These sentinel surveillance estimates can be used to guide national congenital syphilis prevention efforts.
Factors associated with high transmission risk and detectable plasma HIV RNA in HIV-infected MSM on ART
Authors: Blumenthal Jill , Haubrich Richard , Jain Sonia , Sun Xiaoying , Dube Michael , Daar Eric , Milam Joel , Morris Sheldon 
Published: January 2014

Summary HIV transmission risk is increased during antiretroviral therapy (ART) use if individuals are not virologically suppressed and engage in high risk transmission behaviour. Baseline data of HIV-infected men who have sex with men (MSM) with recent history of risky behaviour on ART for ≥3 months ( n = 139) were evaluated to assess predictors of detectable viraemia and HIV transmission risk-taking behaviour. Twenty-four subjects had viral load (VL) >75 copies/mL and 12 had VL >1000 copies/mL. In multivariable regression analyses, subjects with VL >75 copies/mL were more likely to be Black (OR = 4.48, p = 0.007), have lower CD4 cell counts (OR = 0.727, p = 0.005) and have used methamphetamines in the last month (OR = 6.64, p = 0.019). Subjects with VL >1000 copies/mL were more likely to have lower CD4 cell counts (OR = 0.494, p = 0.004), report <90% adherence (OR = 7.94; p = 0.046) and have used methamphetamines in the last month (OR = 10.01, p = 0.034). Subjects with VL >75 copies/mL with the greatest transmission risk behaviour ( n = 14) were more likely to be Black (OR = 8.00, p = 0.006), have lower CD4 cell counts (OR = 0.657, p = 0.009) and have used methamphetamines in the last month (OR = 5.20, p = 0.042). High risk HIV transmission behaviour with viraemia occurred in 10% of the cohort. Future efforts to reduce HIV transmission among MSM on ART will require combined interventions that target risk-taking behaviours and substance use.
Neuropsychiatric systemic lupus erythematosus: association with global disease activity
Authors: Morrison E , Carpentier S , Shaw E , Doucette S , Hanly JG 
Published: January 2014

Objective To determine whether patients with neuropsychiatric (NP) events attributed to systemic lupus erythematosus (SLE) have more global disease activity than patients with NP events not attributed to SLE. Methods Patients were recruited from an academic lupus clinic. Global disease activity was measured with the SLE Disease Activity Index 2000 (SLEDAI-2K) and organ damage with the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) damage index (SDI). NP disease was defined using the ACR case definitions and decision rules for attribution of NP events to SLE and non-SLE causes. Results There were 68 patients (age (mean ± SD) 40.8 ± 15.2 years, 85% female, 94% Caucasians) with 126 NP events. SLEDAI-2K scores in patients with NP events attributed to SLE were higher than in patients with NP events attributed to non-SLE causes even when NP variables were removed from the SLEDAI-2K (mean ± SD: SLE NP = 7.36 ± 5.42 vs non-SLE NP = 5.53 ± 4.57, P = 0.042). Patients with CNS and diffuse NP events, rather that PNS and focal events, accounted for the group differences in SLEDAI-2K scores. There were no significant differences in total SDI scores comparing NP events due to SLE vs. non-SLE causes (mean ± SD: 2.1 ± 1.8 vs. 1.7 ± 1.7; p = 0.28) even when NP variables were omitted. Conclusions Increased global SLE disease activity is associated with concurrent NP events attributed to SLE, particularly for diffuse NP and CNS NP events. The findings have diagnostic and therapeutic implications for SLE patients with NP events and inform pathogenetic mechanisms underlying NPSLE.
Managerial Skills of Hospital Administrators
Authors: Toygar Sukru Anil , Akbulut Yasemin 
Published: January 2014

The aim of this study is to identify the decision-making and problem-solving skill levels of hospital administrators and to determine these skills’ interrelations with other administrative skills. The study comprised a population of 494 hospital administrators (head doctors, hospital managers, head nurses and their assistants) and was carried out in 26 hospitals affiliated to the Ministry of Health in the city centre of Ankara. Three hundred and thirty-four administrators (67 per cent of the population) participated in the study. To identify the decision-making, problem-solving and other administrative skill levels of the hospital administrators, a scale developed by Sperry (2003) and adapted into Turkish by Şimşek (2006) was used. As a result of the study; a weak, positive and statistically significant relationship has been found between the decision-making and problem-solving skills of hospital administrators and their motivation, loyalty and team performance skills. However, it was determined that there is a moderate, positive and statistically significant relationship between the skills of the delegation and empowerment, effective and strategic communication, conflict management, coaching, consulting and negotiating, the fit of organizational resources with human resources, and time and stress management. It could be suggested that more research be carried out into the reasons why other management skills are at moderately developed levels and that training programmes be organized to develop these skills.
Predicting Hyperhomocysteinemia by Methylenetetrahydrofolate Reductase C677T Polymorphism in Chinese Patients With Hypertension
Authors: Wang Yu , Xu Xin , Huo Yong , Liu Dahai , Cui Yimin , Liu Zeyuan , Zhao Zhigang , Xu Xiping , Liu Lisheng , Li Xiaoying , Jiang Shanqun 
Published: January 2014

Objective: To evaluate the performance of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism in predicting hyperhomocysteinemia (HHcy) in Chinese patients with hypertension. Methods: We measured plasma total homocysteine tHcy level and C677T genotype in 1058 Chinese patients with hypertension from 4 previous studies. We used 10, 15, and 20 μmol/L as cutoff values for the definition of mild, modest, and severe HHcy, respectively. Logistic models for HHcy were built from the study sample using the C677T genotype as well as age and gender as predictors. The receiver–operating characteristics of the models were evaluated. Results: Our major findings are that (1) C677T TT genotype is consistently associated with a higher tHcy across the 4 studies, with an increase in size ranging from 38% to 68% in the 4 studies and 51% overall. The C677T polymorphism independently explained about 14% of the total variance of the normalized tHcy. (2) The TT genotype is associated with a large increase in odds ratio (OR) for HHcy. Overall, the multivariate-adjusted ORs for the TT genotype are 3.9 (95% confidence interval [CI]: 2.4-6.4), 6.5 (95% CI: 4.0-10.6), and 17.9 (95% CI: 8.4-38.1) for mild, modest, and severe HHcy, respectively. (3) Overall, the predicting performance increased with HHcy severity, with sensitivity improving from 31.0% for mild HHcy to 70.3% for severe HHcy, and with specificity slightly decreasing from 85.4% to 80.3%. Inclusion of gender and age as predictors significantly improves the sensitivity, especially for predicting mild HHcy. Conclusion: With an excellent sensitivity and a modest specificity, C677T could be a useful screening marker for severe HHcy.
Angiotensin IV and the human esophageal mucosa: An exploratory study in healthy subjects and gastroesophageal reflux disease patients
Authors: Björkman Eleonora , Edebo Anders , Fändriks Lars , Casselbrant Anna 
Published: January 2014

Introduction: The human esophageal mucosa expresses various components of the renin-angiotensin system (RAS), e.g. the main effector peptide angiotensin II (AngII). The aim of this study was to investigate the esophageal presence of angiotensin III (AngIII) and angiotensin IV (AngIV) forming enzymes and the AngIV receptor (AT4R). The aim was also to study the actions of AngIV and to look for aberrations in patients with gastroesophageal reflux disease (GERD). Materials and methods: Esophageal biopsies were collected from healthy volunteers ( n: 19) and individuals with erosive reflux disease ( n: 14). Gene transcripts and protein expression of aminopeptidase A, -B and -M, and the AT4R were investigated by reverse transcriptase polymerase chain reaction (rt-PCR), western blot (WB) and immunohistochemistry (IHC). The functional impact of AngIV was examined in an Ussing chamber. Results: Aminopeptidase A, -B and -M and the AT4R were expressed in the esophageal epithelium. The AT4R was less prominent in certain areas in the mucosa of reflux patients. AngIV influenced the esophageal epithelial ion transport. The impact was lower in patients with GERD. Conclusion: The AT4R and formation enzymes of AngIII and AngIV are present in the human esophageal epithelium. Moreover, the present results suggest that AngIV exert regulatory impact on the epithelium and that RAS is involved in mucosal aberrations associated with GERD.
Novel variants detected in AGT gene among patients with essential hypertension
Authors: Padma G , Charita Bh , Swapna N , Mamata M , Padma T 
Published: January 2014

Introduction: AGT is the first gene to be linked to essential hypertension (EHT). It harbors several variants of which only few polymorphisms are found to exhibit positive and negative associations with hypertension. In the present study, the AGT gene was screened to detect already reported and novel variations contributing to the development of hypertension. Method: In total, 215 hypertensives and 230 normotensives were screened for variations in all the five exons and a part of promoter of AGT gene using single strand conformation polymorphism analysis followed by sequencing of samples showing mobility shifts on polyacrylamide gels. Results: Five novel variants, namely c.-61G>A in promoter, c.-4+17C>T in intron1, c.24T>C and c.28A>T in Exon2, and c.*90 T>C in 3’ untranslated region were detected in the AGT gene. c.-61G>A lies in the promoter region that plays a critical role in its expression. Variation c.-4+17C>T created a new enhancer site. c.24T>C (TCT-TCC) is a silent mutation while c.28A>T (p. M10L) has a possible damaging effect on the AGT protein. c.*90T>C, detected in the 3’ untranslated region is thought to play an important role in the translation and stability of the mRNA. Conclusion: Studies on the functional role of these novel variants are warranted to understand the mechanism underlying the development of EHT.
Association of ACE and MTHFR genetic polymorphisms with type 2 diabetes mellitus: Susceptibility and complications
Authors: Settin Ahmad , El-Baz Rizk , Ismaeel Azza , Tolba Wafaa , Allah Wafaa A 
Published: January 2014

Hypothesis/introduction: Polymorphisms of angiotensin converting enzyme ( ACE) and methylene-tetrahydrofolate reductase ( MTHFR) genes have been proposed to be associated with type 2 diabetes mellitus (T2DM) with conflicting results. This work was planned in order to check for the association of these polymorphisms with the susceptibility for and complications of T2DM among Egyptian cases. Materials and methods: This is a case controlled study involving 203 patients with T2DM and 311 healthy controls. Polymorphic variants of ACE I>D and MTHFR ( 677 C>T and 1298 A>C) were determined using the polymerase chain reaction (PCR) restriction analysis technique. Results: The susceptibility to T2DM was higher among subjects having the MTHFR 677TT (odds ratio (OR)=2.2, p=0.01), MTHFR 1298 AA (OR=1.84, p=0.001) and ACE (ID+II) (OR=2.0, p=0.0007) genotypes. Logistic regression analysis showed that MTHFR 677T allele was a risk factor for diabetic retinopathy (DR) (OR=3.47, p<0.001), diabetic polyneuropathy (DPN) (OR=5.2, p<0.0001) and ischemic heart disease (IHD) (OR=2.9, p<0.05), while MTHFR 1298 C allele was a risk factor for DR (OR=4.2, p<0.001) and the ACE DD genotype was a risk factor for DPN (OR=3.1, p<0.001). Conclusions: The MTHFR 677 TT genotype was associated with T2DM susceptibility and complications (DR, DPN and IHD). The MTHFR 1298 CC, AC and ACE DD genotypes were associated with DR and DPN.
The peripheral cannabinoid receptor 1 antagonist VD60 efficiently inhibits carbon tetrachloride-intoxicated hepatic fibrosis progression
Authors: Wei Yan , Kang Xiao-li , Wang Xu 
Published: January 2014

This study investigated a peripheral selective CB1antagonist 3,4,22-3-demethoxycarbonyl-3-hydroxylmethyl-4-deacetyl-vindoline 3,4-thionocarbonate (VD60) that efficiently inhibited hepatic fibrosis with lower psychological side effects. A competitive radiolabeled ligand binding experiment and 3′-5′-cyclic adenosine monophosphate (cAMP) response element-driven luciferase analysis were performed to evaluate the antagonistic activity of VD60. Cell viability and collagen production were examined in the human hepatic stellate cell (HSC) line LX-2 and primary cultured rat HSCs. The antifibrotic effects of VD60 were investigated in a CCl4-induced liver fibrosis mouse model. The concentration of VD60 in the blood and the brain was determined by high-performance liquid chromatography–mass spectrum analysis. Furthermore, the potential underlying mechanisms of VD60 were investigated by Western blot. VD60 selectively competed with the radiolabeled CB1agonist to bind to CB1. VD60 antagonized CB1agonist-induced Akt phosphorylation and increased the accumulation of intracellular cAMP. VD60 strongly reduced the expression of α2(I) pro-collagen mRNA and exerted potent antiproliferative effects on primary HSCs and LX-2 cells. The inhibition of reactive oxygen species production and phosphorylation of Akt, extracellular-signal-regulated kinase (ERK), and Smad3 may explain the underlying mechanisms behind the antiproliferative effect of VD60. Moreover, the in vivo antifibrotic activity of VD60 was confirmed in a CCl4-induced liver fibrosis mouse model. Most importantly, the concentration of VD60 in the peripheral blood was much higher than in the brain, suggesting that VD60 could act as a novel peripheral CB1antagonist to efficiently inhibit hepatic fibrosis and could be used as a lead compound with low brain side effects in peripheral antifibrotic agents.
Considerations in the design of randomized trials to screen for type 2 diabetes
Authors: Echouffo-Tcheugui Justin B , Prorok Philip C 
Published: January 2014

Background Randomized controlled trials (RCTs) are the most robust and valid approach to evaluate screening for diseases. Many in the diabetes research community have advocated sole reliance on RCTs for designing diabetes screening policies. However, the challenges of conducting RCTs of screening for type 2 diabetes may have been underappreciated. Purpose Discuss the key theoretical concepts and practical challenges of designing and conducting RCTs of diabetes screening. Methods Narrative and critical review of the literature pertaining to the theory and practice of designing and conducting RCTs of diabetes screening. Results We present the theoretical basis of a diabetes screening trial, using concepts developed mainly in studies of cancer screening and illustrations from the Cambridge component of the Anglo Danish Dutch Study of Intensive Treatment In peOple with screeN-detected diabetes in primary care (ADDITION-Cambridge), the only extant trial of diabetes screening. We examine design issues, including the appropriate trial question, choice of design, and duration of follow-up, and address aspects of trial implementation, including recruitment, randomization, endpoint determination, sample size requirements, and screening interval. Limitations The limited number of trials of diabetes screening did not permit us to illustrate many of the practical difficulties one encounters when implementing theoretical concepts. Conclusion When diabetes screening trials are planned, we suggest careful consideration to potential areas of practical difficulty, especially the need for particularly large sample sizes and extended follow-up, and the choice of appropriate outcomes and screening intervals.
Effect of Force of Microneedle Insertion on the Permeability of Insulin in Skin
Authors: Cheung Karmen , Han Tao , Das Diganta Bhusan 
Published: January 2014

Background: Many experiments conducted in the literature have investigated the effect of microneedles (MNs) on insulin permeation across skin. There are also a number of articles that deal with the effect of MN insertion force in skin. However, there is little known on quantifying the relationship between the effect of MN insertion force and the amount of insulin permeated for given MNs. This issue is addressed in this article. Methods: MNs of 1100 µm and 1400 µm are used to conduct in vitro permeability experiments on porcine skin, using insulin. Histological images of MN treated skin are obtained from a microtome and the viscoelastic properties of the skin sample are measured using a rheometer. An in-house insertion force device is utilized that can reproducibly apply a specified force on MNs for a set period of time using compressed air. Results: It is deduced that when porcine skin was pretreated with an applied force of 60.5 N and 69.1 N, the resultant amount of insulin permeated was approximately 3 µg and 25 µg over a 4-hour period for the MNs used. Conclusions: The amount of MN force applied to porcine skin was shown to be related to the amount of insulin permeated. An increase in insertion force increase the amount of insulin permeated. It was also demonstrated that using insufficient force may have reduced or prevented the amount of insulin passing through the skin, regardless of the geometry of the MNs.
Phase 2 study of VcR-CVAD with maintenance rituximab for untreated mantle cell lymphoma: an Eastern Cooperative Oncology Group study (E1405)
Authors: Chang Julie E. , Li Hailun , Smith Mitchell R. , Gascoyne Randy D. , Paietta Elisabeth M. , Yang David T. , Advani Ranjana H. , Horning Sandra J. , Kahl Brad S. 
Published: January 2014

Key PointsVcR-CVAD produced high overall and CR rates in previously untreated MCL patients. No substantial difference in 3-year PFS or OS was observed in patients receiving ASCT compared with patients receiving maintenance rituximab.
Generalized α-ψ contractive mappings in quasi-metric spaces and related fixed-point theorems
Authors: Bilgili Nurcan , Karapınar Erdal , Samet Bessem 
Published: January 2014

Abstract
In this paper, we characterize α-ψ contractive mappings in the setting of quasi-metric spaces and investigate the existence and uniqueness of a fixed point of such mappings. We notice that by using our result some fixed-point theorems in the context of G-metric space can be deduced.

MSC:46T99, 47H10, 54H25, 46J10.