bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progression to first‐degree heart block in preschool children exposed in utero to maternal anti‐SSA/Ro52 autoantibodies
Authors: Bergman Gunnar , Eliasson Håkan , Mohlkert Lilly‐Ann , Wahren‐Herlenius Marie , Sonesson Sven‐Erik 
Published: December 2011

AbstractAims:  To study the children exposed in utero to maternal anti‐SSA/Ro52 antibodies in terms of impaired atrioventricular (AV) conduction or disturbed myocardial performance, and to investigate the ability of prenatal Doppler to predict conduction abnormalities during childhood.Methods:  Fifty‐seven children exposed in utero to anti‐SSA/Ro52 antibodies were grouped in accordance with (A) prolonged AV time intervals in utero by Doppler or (B) normal findings and examined by ECG, 24‐hour ECG and echocardiography.Results:  PR interval on ECG was longer in group A (n = 16) compared with that of group B (n = 41), 140 ± 24 ms vs. 121 ± 13 ms (p < 0.01). Six cases of 1°Atrioventricular block (AVB) developed in group A, giving an estimated prevalence of 10.5%, (95% confidence interval; 4.4–22.2%), progressing from normal sinus rhythm at 1 month of age. Prenatal Doppler predicted development of 1°AVB at follow‐up with a sensitivity of 100%, Positive predictive value (PPV) 37.5%, LR+ 5.1, and Negative predictive value (NPV) 100%. Children in group A had a slightly higher myocardial performance index in flow and tissue Doppler imaging recordings.Conclusions:  Ten per cent of children exposed in utero to anti‐SSA/Ro52, with a normal ECG at birth or 1 month of age, progressed to 1°AVB during preschool years. Cases at risk can be identified by prenatal Doppler echocardiography.
Risk of Prion Disease Transmission through Bovine‐Derived Bone Substitutes: A Systematic Review
Authors: Kim Yeoungsug , Nowzari Hessam , Rich Sandra K. 
Published: December 2011

ABSTRACTBackground:Despite the causal association between variant Creutzfeldt – Jakob disease and bovine spongiform encephalopathy (BSE), bovine origin graft materials are widely used during dental surgical procedures. The aim of this study was to assess the risk of BSE transmission through anorganic bovine bone substitutes.Methods:Electronic database of MEDLINE was searched to identify relevant studies regarding our focused questions, presence of BSE prion infectivity in raw bovine bone, BSE prion inactivation by bone substitute manufacturing process, protein contents in anorganic bovine bone substitutes, and validity of current BSE diagnostic methods. Search terms yielded 1,704 titles. After title/abstract screening and duplicates removal, 36 full‐text articles were screened for inclusion.Results:A total of 16 studies were included in the final analysis. No eligible studies were identified regarding the efficacy of BSE prion inactivation by the treatments used for anorganic bovine bone manufacturing. BSE infectivity and PrPSc, pathological prion, were detected in bovine bone marrow and serum samples. Proteins were detected in Tutoplast® (bovine), Bio‐Oss®, and tibia samples treated at the similar condition for Bio‐Oss deproteinization. Inconsistent results of different BSE diagnostic tests were not unusual findings (Iwata et al. 2006; Arnold et al. 2007; Murayama et al. 2010), and a study by Balkema‐Buschmann and colleagues showed an apparent discrepancy between BSE infectivity and detection of PrP(27‐30), the current surrogate marker for prion disease infectivity.Conclusion:This review indicates that bovine‐derived graft biomaterials may carry a risk of prion transmission to patients.
Immediate and Early Loading of Chemically Modified Implants in Posterior Jaws: 3‐Year Results from a Prospective Randomized Multicenter Study
Authors: Nicolau Pedro , Korostoff Jonathan , Ganeles Jeffrey , Jackowski Jochen , Krafft Tim , Neves Manuel , Divi Jose , Rasse Michael , Guerra Fernando , Fischer Kerstin 
Published: December 2011

ABSTRACTBackground: There is a lack of well‐designed prospective, randomized clinical trials evaluating the efficacy of immediate and early loading of implants placed in the partially edentulous posterior maxilla or mandible.Purpose: The aim of this study was to evaluate crestal bone level changes over 3 years following immediate or early loading of Straumann implants with a chemically modified surface (SLActive®, Institut Straumann AG, Basel, Switzerland) placed in the posterior maxilla and mandible.Materials and Methods: Subjects received temporary restorations immediately or 28 to 34 days after surgery, with permanent restorations placed at 20 to 23 weeks. Bone level changes were measured by comparison of standardized radiographs taken on the day of implant placement and 5, 12, 24, and 36 months thereafter.Results: Two hundred thirty‐nine of two hundred sixty‐six patients (89.9%) completed the trial. Implant survival rates were 97.4% and 96.7% in the immediate and early loading groups, respectively (p = not significant). Over 36 months, the mean bone level change for immediately loaded implants was 0.88 ± 0.81 mm versus 0.57 ± 0.83 mm for the early‐loaded group (p < .001). After adjusting for a slight difference in initial placement depth, the time of loading had no significant influence on bone level change.Conclusions: Changes in crestal bone level occurred mostly during the first 5 months postloading. After this bone remodeling period, crestal bone level was stable up to 36 months. Implants with a chemically modified surface are safe and predictable for immediate and early loading in the posterior maxilla and mandible.
The Influence of Verification Jig on Framework Fit for Nonsegmented Fixed Implant‐Supported Complete Denture
Authors: Ercoli Carlo , Geminiani Alessandro , Feng Changyong , Lee Heeje 
Published: December 2011

ABSTRACTPurpose: The purpose of this retrospective study was to assess if there was a difference in the likelihood of achieving passive fit when an implant‐supported full‐arch prosthesis framework is fabricated with or without the aid of a verification jig.Materials and Methods: This investigation was approved by the University of Rochester Research Subject Review Board (protocol #RSRB00038482). Thirty edentulous patients, 49 to 73 years old (mean 61 years old), rehabilitated with a nonsegmented fixed implant‐supported complete denture were included in the study. During the restorative process, final impressions were made using the pickup impression technique and elastomeric impression materials. For 16 patients, a verification jig was made (group J), while for the remaining 14 patients, a verification jig was not used (group NJ) and the framework was fabricated directly on the master cast. During the framework try‐in appointment, the fit was assessed by clinical (Sheffield test) and radiographic inspection and recorded as passive or nonpassive.Results: When a verification jig was used (group J, n = 16), all frameworks exhibited clinically passive fit, while when a verification jig was not used (group NJ, n = 14), only two frameworks fit. This difference was statistically significant (p < .001).Conclusions: Within the limitations of this retrospective study, the fabrication of a verification jig ensured clinically passive fit of metal frameworks in nonsegmented fixed implant‐supported complete denture.
Cognitive function and clinical symptoms in first‐episode psychosis and chronic schizophrenia before and after the 2009 L'Aquila earthquake
Authors: Pollice Rocco , Bianchini Valeria , di Mauro Stefania , Mazza Monica , Verni Laura , Roncone Rita , Casacchia Massimo 
Published: December 2011

AbstractAim: On 6 April 2009, at 3:32 GMT, central Italy was struck by a 6.3‐magnitude earthquake with its epicentre near L'Aquila, the capital city of the Abruzzo region. Earthquakes may precipitate psychiatric symptoms. The aim of this study was to investigate cognitive functioning and positive and negative symptoms before and after the 2009 L'Aquila earthquake in patients with first‐episode psychosis (FEP) and chronic schizophrenia (CS).Methods: A total of 54 FEP patients (34 males and 20 females) and 63 CS patients (39 males and 24 females) were investigated. Psychometric scores were submitted to a 2 × 2 mixed analysis of variance, with group (FEP and CS) as the between‐subjects variable and time (pre‐ and post‐earthquake) as the within‐subjects variable.Results: Positive symptoms increased significantly from the pre‐ to the post‐earthquake assessment in FEP patients but not in those with CS. There were no significant differences between the pre‐ and post‐earthquake period in terms of negative symptoms in both groups. Compared with the pre‐earthquake assessment, FEP patients scored significantly worse at the post‐earthquake evaluation in terms of Wisconsin Card Sorting Test categories achieved, immediate verbal memory and delayed verbal memory. However, there were no significant differences in cognitive scores between the pre‐ and post‐earthquake periods in patients with CS.Conclusions: Our findings suggest that a disastrous earthquake has a negative impact on cognitive functioning and positive symptoms in FEP patients, but not in those with CS.
Outbreaks of Attacks by Hematophagous Bats in Isolated Riverine Communities in the Brazilian Amazon: A Challenge to Rabies Control
Authors: Carvalho‐Costa F. A. , Tedesqui V. L. , de Jesus Nascimento Monteiro M. , Bóia M. N. 
Published: December 2011

SummaryHuman rabies has re‐emerged in Latin America due to bat associated transmission. We present data related to attacks by hematophagous bats in three riverine communities in the Rio Negro basin, Brazilian Amazon. A cross‐sectional survey was carried out to obtain demographic and epidemiological data through interviews with 201 inhabitants. A total of 721 bat attacks with bites took place from 2004 to 2006, 238 (33%) reported by residents in Campinas do Rio Preto, 329 (46%) in Águas Vivas and 154 (21%) in the community of Malalahá. Incidence density among surveyed inhabitants was 84 attacks/100 persons‐years in Campinas do Rio Preto, 249 attacks/100 persons‐years in Águas Vivas and 81 attacks/100 persons‐years in Malalahá. The proportion of surveyed inhabitants bled by bats at least once was 67% (63/94) in Campinas do Rio Preto, 96% (42/44) in Águas Vivas and 62% (39/63) in Malalahá. Among subjects bled by bats, the average number of bites was 4.6 ± 4.2 standard deviations (SD) in Campinas do Rio Preto, 8 ± 6 SD in Águas Vivas and 4.1 ± 3.9 SD in Malalahá. Regarding houses, 67% (26/39) had animals in the peridomestic environment (chickens and/or dogs) and all were vulnerable to bats due to gaps in the walls and/or in the windows and doors. In 13 dwellings, rudimentary protection against bats through the fixation of fishing nets and/or straw nets to the windows and other openings was observed. Among dwellers reporting attacks, 48% (68/144) received the full post‐exposure anti‐rabies vaccination protocol with five doses of diploid human cell vaccine, 28% (39/144) received an incomplete schedule (1–4 doses), and 26% (37/144) did not receive any dose. No cases of rabies were reported during the study; however, regular pre‐exposure vaccination in the studied populations must be considered.
Protective hepatitis B surface antibodies in blood and ascites fluid in the early stage after liver transplantation for hepatitis B diseases
Authors: Wang Kai , Zhu Zhi‐Jun , Zheng Hong , Deng Yong‐Lin , Pan Cheng , Sun Li‐Ying , Shen Zhong‐Yang 
Published: December 2011

Aim:  The aim of this study is to identify the titres of protective hepatitis B surface antibodies (anti‐HBs) in the blood and their effective factors in the early stage after liver transplantation (LT) for hepatitis B virus (HBV) related diseases. The condition of anti‐HBs lost in ascites fluid was also investigated.Methods:  Twenty‐six patients who received LT were administered prophylaxis of lamivudine combining intravenous hepatitis B immunoglobulin (HBIG) post‐LT. The titres of anti‐HBs were recorded and analyzed daily in blood and ascites fluid within the first week post‐LT.Results:  In the first 5 days post‐LT, the titres of anti‐HBs in HBV DNA positive groups, high hepatitis B surface antigen (HBsAg) groups, hepatitis B e antigen (HBeAg) positive groups were lower than that in the parallel HBV DNA negative groups, low HBsAg groups and HBeAg negative groups. The mean titre level of anti‐HBs in ascites fluid is 224.89 IU/L and fluctuated from 0.00 IU/L to 968.50 IU/L, which is also correlated with anti‐HBs titres in blood drawn at the same time (r = 0.927, P = 0.000). The level of anit‐HBs in ascites fluid was very high; however, it fluctuated in a wide range (from 0.00 IU to 908.55 IU).Conclusions:  Patients in high risk groups should receive a higher level of HBIG to maintain sufficient amounts of anti‐HBs in the early stage post‐LT, while the patients in low risk groups need a lower level of HBIG administration. Furthermore, the lost amount of anti‐HBs in ascitic fluid post‐LT has minimum impact on the anti‐HBs titres in blood.
High fat diet induced hepatic steatosis and insulin resistance: Role of dysregulated ceramide metabolism
Authors: Longato Lisa , Tong Ming , Wands Jack R. , de la Monte Suzanne M. 
Published: December 2011

Aim:  Non‐alcoholic fatty liver disease (NAFLD) is an insulin resistance disease that can progress to cirrhosis and liver failure. We hypothesized that in NAFLD, insulin resistance dysregulates lipid metabolism, increasing production of cytotoxic lipids including ceramides, which exacerbate hepatic insulin resistance and injury.Methods:  Long Evans rats were pair‐fed low (LFD) or high (HFD) fat diets for 8 weeks. Livers were used to measure lipids, gene expression, insulin receptor binding, integrity of insulin signaling, and pro‐inflammatory cytokines. In vitro experiments characterized effects of ceramides on Huh7 cell viability, mitochondrial function, and insulin signaling.Results:  High fat diet feeding caused NAFLD with peripheral and hepatic insulin resistance, increased hepatic expression of pro‐ceramide genes, sphingomyelinase activity, and lipid peroxidation, and increased serum ceramide. Ceramide treatment impaired Huh7 cell viability, mitochondrial function, and insulin signaling.Conclusions:  Increased hepatic ceramide generation and release may mediate both hepatic and peripheral insulin resistance in NAFLD.
Pharmacokinetic study of liposome-encapsulated and plain mepivacaine formulations injected intra-orally in volunteers
Authors: Tofoli Giovana Radomille , Cereda Cíntia M S , Araújo Daniele Ribeiro , Franz-Montan Michelle , Groppo Francisco Carlos , Quaglio Daiane , Pedrazzoli Junior Jose , Calafatti Silvana Aparecida , Barros Fabio Alessandro Proença , de Paula Eneida 
Published: December 2011

Abstract

Objectives
The pharmacokinetics of commercial and liposome-encapsulated mepivacaine (MVC) injected intra-orally in healthy volunteers was studied.

Methods
In this double blind, randomized cross-over study, 15 volunteers received, at four different sessions, 1.8 ml of the following formulations: 2% MVC with 1 : 100 000 epinephrine (MVC2%EPI), 3% MVC (MVC3%), 2% and 3% liposome-encapsulated MVC (MVC2%LUV and MVC3%LUV). Blood samples were collected pre dose (0 min) and at 15, 30, 45, 60, 90, 120, 180, 240, 300, 360 min after injections. Liquid chromatography-tandem mass spectrometry was used to quantify plasma MVC concentrations.

Results
Pharmacokinetic analysis showed that the maximum plasma concentration (Cmax) and the areas under the curves (AUC0–360 and AUC0–∞) after MVC2%LUV and MVC2%EPI injections were smaller (P &lt; 0.05) than the equivalent figures for MVC3% and MVC3%LUV. The time to maximum plasma concentration (Tmax) and the half-life of elimination (t½beta) obtained after the treatment with MVC2%LUV, MVC2%EPI, MVC3% and MVC3%LUV presented no statistically significant differences (P &gt; 0.05). Cmax, AUC0–360 and AUC0-∞ after injection of the 2% formulations (MVC2%LUV and MVC2%EPI) did not exhibit statistically significant differences (P &gt; 0.05). The pharmacokinetics of MVC2%LUV were comparable to the pharmacokinetics of MVC2%EPI.

Conclusion
The liposomal formulation of 2% MVC exhibits similar systemic absorption to the local anesthetic with vasoconstrictor.
Monocytic CCR2+ Myeloid-Derived Suppressor Cells Promote Immune Escape by Limiting Activated CD8 T-cell Infiltration into the Tumor Microenvironment
Authors: Lesokhin Alexander M. , Hohl Tobias M. , Kitano Shigehisa , Cortez Czrina , Hirschhorn-Cymerman Daniel , Avogadri Francesca , Rizzuto Gabrielle A. , Lazarus John J. , Pamer Eric G. , Houghton Alan N. , Merghoub Taha , Wolchok Jedd D. 
Published: December 2011

AbstractMyeloid-derived suppressor cells (MDSC) are a heterogeneous population of cells that accumulate during tumor formation, facilitate immune escape, and enable tumor progression. MDSCs are important contributors to the development of an immunosuppressive tumor microenvironment that blocks the action of cytotoxic antitumor T effector cells. Heterogeneity in these cells poses a significant barrier to studying the in vivo contributions of individual MDSC subtypes. Herein, we show that granulocyte-macrophage colony stimulating factor, a cytokine critical for the numeric and functional development of MDSC populations, promotes expansion of a monocyte-derived MDSC population characterized by expression of CD11b and the chemokine receptor CCR2. Using a toxin-mediated ablation strategy to target CCR2-expressing cells, we show that these monocytic MDSCs regulate entry of activated CD8 T cells into the tumor site, thereby limiting the efficacy of immunotherapy. Our results argue that therapeutic targeting of monocytic MDSCs would enhance outcomes in immunotherapy. Cancer Res; 72(4); 876–86. ©2011 AACR.
Pharmacokinetically Stabilized Cystine Knot Peptides That Bind Alpha-v-Beta-6 Integrin with Single-Digit Nanomolar Affinities for Detection of Pancreatic Cancer
Authors: Kimura Richard H. , Teed Robert , Hackel Benjamin J. , Pysz Marybeth A. , Chuang Courtney Z. , Sathirachinda Ataya , Willmann Jürgen K. , Gambhir Sanjiv S. 
Published: December 2011

AbstractPurpose: Detection of pancreatic cancer remains a high priority and effective diagnostic tools are needed for clinical applications. Many cancer cells overexpress integrin αvβ6, a cell surface receptor being evaluated as a novel clinical biomarker.Experimental Design: To validate this molecular target, several highly stable cystine knot peptides were engineered by directed evolution to bind specifically and with high affinity (3–6 nmol/L) to integrin αvβ6. The binders do not cross-react with related integrin αvβ5, integrin α5β1, or tumor-angiogenesis–associated integrin, αvβ3.Results: Positron emission tomography showed that these disulfide-stabilized peptides rapidly accumulate at tumors expressing integrin αvβ6. Clinically relevant tumor-to-muscle ratios of 7.7 ± 2.4 to 11.3 ± 3.0 were achieved within 1 hour after radiotracer injection. Minimization of off-target dosing was achieved by reformatting αvβ6-binding activities across various natural and pharmacokinetically stabilized cystine knot scaffolds with different amino acid content. We show that the primary sequence of a peptide scaffold directs its pharmacokinetics. Scaffolds with high arginine or glutamic acid content suffered high renal retention of more than 75% injected dose per gram (%ID/g). Substitution of these amino acids with renally cleared amino acids, notably serine, led to significant decreases in renal accumulation of less than 20%ID/g 1 hour postinjection (P &lt; 0.05, n = 3).Conclusions: We have engineered highly stable cystine knot peptides with potent and specific integrin αvβ6-binding activities for cancer detection. Pharmacokinetic engineering of scaffold primary sequence led to significant decreases in off-target radiotracer accumulation. Optimization of binding affinity, specificity, stability, and pharmacokinetics will facilitate translation of cystine knots for cancer molecular imaging. Clin Cancer Res; 18(3); 839–49. ©2011 AACR.
Notch Signaling Modulates Hypoxia-Induced Neuroendocrine Differentiation of Human Prostate Cancer Cells
Authors: Danza Giovanna , Di Serio Claudia , Rosati Fabiana , Lonetto Giuseppe , Sturli Niccolò , Kacer Doreen , Pennella Antonio , Ventimiglia Giuseppina , Barucci Riccardo , Piscazzi Annamaria , Prudovsky Igor , Landriscina Matteo , Marchionni Niccolò , Tarantini Francesca 
Published: December 2011

AbstractProstate carcinoma is among the most common causes of cancer-related death in men, representing 15% of all male malignancies in developed countries. Neuroendocrine differentiation (NED) has been associated with tumor progression, poor prognosis, and with the androgen-independent status. Currently, no successful therapy exists for advanced, castration-resistant disease. Because hypoxia has been linked to prostate cancer progression and unfavorable outcome, we sought to determine whether hypoxia would impact the degree of neuroendocrine differentiation of prostate cancer cells in vitro.Results: Exposure of LNCaP cells to low oxygen tension induced a neuroendocrine phenotype, associated with an increased expression of the transcription factor neurogenin3 and neuroendocrine markers, such as neuron-specific enolase, chromogranin A, and β3-tubulin. Moreover, hypoxia triggered a significant decrease of Notch 1 and Notch 2 mRNA and protein expression, with subsequent downregulation of Notch-mediated signaling, as shown by reduced levels of the Notch target genes, Hes1 and Hey1. NED was promoted by attenuation of Hes1 transcription, as cells expressing a dominant-negative form of Hes1 displayed increased levels of neuroendocrine markers under normoxic conditions. Although hypoxia downregulated Notch 1 and Notch 2 mRNA transcription and receptor activation also in the androgen-independent cell lines, PC-3 and Du145, it did not change the extent of NED in these cultures, suggesting that androgen sensitivity may be required for transdifferentiation to occur.Conclusions: Hypoxia induces NED of LNCaP cells in vitro, which seems to be driven by the inhibition of Notch signaling with subsequent downregulation of Hes1 transcription. Mol Cancer Res; 10(2); 230–8. ©2011 AACR.
Patient mortality in the 12 years following enrolment into a pre-surgical cardiac rehabilitation programme
Authors: Rideout Andrew , Lindsay Grace , Godwin Jon 
Published: December 2011

Objective: This study examined whether involvement in a pre-surgical cardiac rehabilitation programme conferred a long-term survival benefit. Design: Patients randomly allocated to a pre-surgical cardiac rehabilitation programme intervention or a control group were tracked through national databases at a point approximately 12 years later, and all causes of mortality were identified from death records. Kaplan–Meier survival analyses based on involvement in a cardiac rehabilitation programme and known pre-surgical risk factors were carried out. Setting: Two health boards in the west of Scotland, referring to a single cardiothoracic tertiary centre. Subjects: Patients admitted to the waiting list for coronary artery bypass surgery. Interventions: Patients were randomly allocated to a control group (‘usual’ care) or an intervention group (nurse-led cardiac rehabilitation) in the pre-operative phase. They were followed up at 12 years post surgery. Main measures: The only outcome measure used for analysis was survival. Measures of anxiety and depression, and physiological and lifestyle risk factors were included as independent variables in analysis of death. Results: The initial study included 110 patients – none were lost to follow-up. Relative risk of death associated with inclusion in the cardiac rehabilitation programme was 0.814; risk of death increased with increasing pre-surgical depression (RR 1.07) and anxiety (RR 1.09). Conclusions: Undertaking pre-surgical cardiac rehabilitation confers a long-term survival advantage over patients not offered this service. Increased anxiety and depression in the pre-surgical phase are additional risk factors for increased mortality.