bluuebunny/crossref_metadata_2025_split huggingface dataset:
Community‐Based Participatory Research Skills and Training Needs in a Sample of Academic Researchers from a Clinical and Translational Science Center in the Northeast
Authors: DiGirolamo Ann , Geller Alan C. , Tendulkar Shalini A. , Patil Pratima , Hacker Karen 
Published: March 2012

AbstractPurpose: To determine the community‐based participatory research (CBPR) training interests and needs of researchers interested in CBPR to inform efforts to build infrastructure for conducting community‐engaged research.Method: A 20‐item survey was completed by 127 academic health researchers at Harvard Medical School, Harvard School of Public Health, and Harvard affiliated hospitals.Results: Slightly more than half of the participants reported current or prior experience with CBPR (58 %). Across all levels of academic involvement, approximately half of the participants with CBPR experience reported lacking skills in research methods and dissemination, with even fewer reporting skills in training of community partners. Regardless of prior CBPR experience, about half of the respondents reported having training needs in funding, partnership development, evaluation, and dissemination of CBPR projects. Among those with CBPR experience, more than one‐third of the participants wanted a mentor in CBPR; however only 19 % were willing to act as a mentor.Conclusions: Despite having experience with CBPR, many respondents did not have the comprehensive package of CBPR skills, reporting a need for training in a variety of CBPR skill sets. Further, the apparent mismatch between the need for mentors and availability in this sample suggests an important area for development. Clin Trans Sci 2012; Volume #: 1–5
Outcomes of moderate sedation in paediatric dental patients
Authors: Özen B , Malamed SF , Cetiner S , Özalp N , Özer L , Altun C 
Published: March 2012

AbstractBackground:  The aim of this study was to evaluate the outcomes of moderate sedation with nitrous oxide/oxygen (N2O/O2) alone or combined with different dosages and administration routes of midazolam in uncooperative paediatric dental patients using the Bispectral Index System (BIS).Methods:  This one‐year clinical study examined first‐visit moderate sedation performed in 240 healthy children aged 4–6 years. Subjects were randomly divided into four groups according to drug, route and dosage, as follows: Group 1 – 0.20 mg/kg midazolam (40 mg/ml) delivered intranasally; Group 2 – 0.75 mg/kg midazolam (15 mg/3 ml) delivered orally; Group 3 – 0.50 mg/kg midazolam (15 mg/3 ml) delivered orally. All children in these three groups also received inhalation sedation with 50%–50% N2O/O2, whereas children in Group 4 received inhalation sedation with 50%–50% N2O/O2 only. The outcome of sedation was evaluated as either ‘successful’, ‘failed’ or ‘not accepted’.Results:  The highest success rate was found in Group 1 (0.20 mg/kg intranasally, 87%), followed by Group 2 (0.75 mg/kg orally, 79%). The overall mean success rate for all groups was 73%.Conclusions:  Moderate sedation can be successfully used in the clinical management of paediatric dental patients, with both intranasal and oral sedation using midazolam in conjunction with nitrous oxide found to be effective methods.
Histology obtained by needle biopsy gives additional information on the prognosis of hepatocellular carcinoma
Authors: van Malenstein Hannah , Komuta Mina , Verslype Chris , Vandecaveye Vincent , Van Calster Ben , Topal Baki , Laleman Wim , Cassiman David , Van Steenbergen Werner , Aerts Raymond , Vanbeckevoort Dirk , Bielen Didier , Pirenne Jacques , van Pelt Jos , Roskams Tania , Nevens Frederik 
Published: March 2012

Aim:  Hepatocellular carcinomas (HCC) have a strong biological heterogeneity. Current prognostic scores do not include histology. Information on the behavior of HCC based on histology has been characterized on retrospective data and large tissue specimens. We aimed to assess the additional value of needle biopsy and keratin 19 (K19) assessment in a prospective manner.Methods:  Between 2003 and 2008, all patients with a confirmed diagnosis of HCC by a percutaneous or laparoscopic needle biopsy at the time of diagnosis, and of Barcelona Clinic Liver Cancer (BCLC) stage A, B or C, were included. The exclusion criterion was a palliative setting. Biopsies were scored for microvascular invasion, differentiation, K19, epithelial cell adhesion molecule and α‐fetoprotein staining. Clinical and radiological features were registered at time of biopsy. The added value of K19 was assessed using Cox proportional hazards regression.Results:  Of 74 patients screened, we included 58 patients. Based on the BCLC, 41% presented with early disease (BCLC A), 16% with intermediate disease (BCLC B) and 43% with advanced disease (BCLC C). In nine patients (16%), K19 staining was positive. Median follow up was 54 months (range 1–74) and 43 patients (72%) died. BCLC classification predicted the prognosis accurately, but histology offered additional prognostic information. In multivariate analysis, K19 was a strong predictor of overall survival (hazard ratio 4.57, 95% confidence interval 1.86–10.6), which improved predictive performance. No needle tract dissemination was observed.Conclusion:  Despite the possible problem of sampling error, needle biopsy offered additional prognostic information. This is especially the case for K19 staining.
Notch‐dependent expression of epithelial–mesenchymal transition markers in cholangiocytes after liver transplantation
Authors: Liu Xiaowei , Li Jun , Xiong Jun , Li Min , Zhang Yong , Zheng Qichang 
Published: March 2012

Aim:  Epithelial–mesenchymal transition (EMT) has been identified in chronic cholestatic liver diseases, which are characterized by biliary proliferation and fibrosis. Activation of Notch signaling mediates EMT in a variety of epithelial cell types. In the present study, we investigated the role of Notch signaling in the regulation of EMT marker expression in cholangiocytes after liver transplantation.Methods:  Orthotopic liver transplantation was performed in Sprague–Dawley rats. Liver tissues and isolated cholangiocytes were collected 1 week after transplantation. The expression of mesenchymal and biliary epithelial markers was evaluated by immunohistochemistry, quantitative polymerase chain reaction (PCR) and western blotting in liver sections and isolated cholangiocytes. Quantitative real‐time PCR and western blotting for Jagged1 and HES1 were utilized to evaluate the activation of Notch signaling. Proliferation and migration of cholangiocytes were assessed by 5‐bromodeoxyuridine and transwell assays, respectively. Cholangiocyte proliferation, migration and expression of EMT markers were also evaluated following the inhibition of Notch signaling with N,(N‐[3,5‐difluorophenacetyl]‐L‐alanyl)‐S‐phenylglycine t‐butylester (γ‐secretase inhibitor) and a Jagged1‐neutralizing antibody.Results:  Expression of EMT markers by cholangiocytes was observed in liver grafts and isolated cholangiocytes obtained 1 week after transplantation. Inhibition of Notch signaling prevented the expression of EMT markers in bile ducts of liver sections and isolated cholangiocytes. Cholangiocyte proliferative and migratory capacities were also suppressed by the inhibition of Notch signaling.Conclusion:  Activation of Notch signaling promotes cholangiocyte proliferation and expression of EMT markers after liver transplantation.
Localization of hepatocyte nuclear factor‐4α in the nucleolus and nucleus is regulated by its C‐terminus
Authors: Ogata Makiko , Awaji Takeo , Iwasaki Naoko , Fujimaki Risa , Takizawa Miho , Maruyama Kei , Bell Graeme I , Iwamoto Yasuhiko , Uchigata Yasuko 
Published: March 2012

AbstractAims/Introduction:  Mutations in hepatocyte nuclear factor‐4α (HNF4α) lead to various diseases, among which C‐terminal deletions of HNF4α are exclusively responsible for maturity onset diabetes of the young 1 (MODY1). MODY is an autosomal dominant disease characterized by a primary defect in insulin response to glucose, suggesting that the C‐terminus of HNF4α is important for pancreatic β‐cell function. To clarify the role of the C‐terminus of HNF4α, changes in cellular localization and the binding ability to its regulator were examined, specifically in the region containing Q268, which deletion causes MODY1.Materials and Methods:  Cellular localization of mutant HNF4α were examined in monkey kidney 7 (COS7), Chinese hamster ovary, rat insulinoma and mouse insulinoma cells, and their binding activity to other proteins were examined by fluorescence resonance energy transfer (FRET) in COS7 cells.Results:  Although wild‐type HNF4α was localized in the nucleoplasm in transfected cultured cells, Q268X‐HNF4α was located predominantly in the nucleolus. Deletion analysis of the C‐terminus of HNF4α showed that the S337X‐HNF4α mutant, and other mutants with shorter amino acid sequences (S337‐K194), were mostly localized in the nucleolus. HNF4α mutants with amino acid sequences shorter than the W192X‐HNF4α mutant gradually spread to the nucleoplasm in accordance with their lengths. The A250X‐HNF4α mutant was capable of causing the accumulation of HNF4α or the small heterodimer partner (SHP), one of the HNF4α regulators, in the nucleolus. However, the R154X‐HNF4α mutant did not have binding ability to wild‐type HNF4α or SHP, and thus was seen in the nucleus.Conclusions:  The C‐terminus sites might play a key role in facilitating the nucleolar and subnucleolar localization of HNF4α. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2012.00210.x, 2012)
Prolonged hyperinsulinemia after subcutaneous injection of 2400 U regular insulin in a suicide attempt: Time course of serum insulin with frequent measurements
Authors: Hiromine Yoshihisa , Kawabata Yumiko , Yamauchi Takaaki , Noso Shinsuke , Babaya Naru , Harada Takeshi , Ito Hiroyuki , Ikegami Hiroshi 
Published: March 2012

AbstractWe studied the time course of serum insulin level in a patient who injected large amounts of regular insulin in an attempted suicide. A 58‐year‐old woman attempted suicide by subcutaneously injecting herself with 2400 U regular insulin. On arrival, the serum glucose level was 2.4 mmol/L (44 mg/dL) and the serum insulin level was 40,000 pmol/L (5700 μIU/mL). The serum insulin level was high, with a maximum of 110,000 pmol/L (16,000 μIU/mL) at 13 h after injection, followed by an initial rapid decrease and a subsequent slow decrease, with hyperinsulinemia lasting as long as 5 days after injection. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2012.00211.x, 2012)
Biorelevant in-vitro performance testing of orally administered dosage forms
Authors: Reppas Christos , Vertzoni Maria 
Published: March 2012

Abstract

Objectives
This review focuses on the evolution and current status of biorelevant media and hydrodynamics, and discusses the usefulness of biorelevant performance testing in the evaluation of specific dosage form related lumenal processes.

Key findings
During the last 15 years our knowledge of the gastrointestinal environment (including the lower gut) has improved dramatically and biorelevant media composition and, to a lesser extent, biorelevant hydrodynamics, have been refined. Biorelevant dissolution/release testing is useful for the evaluation of formulation and food effects on plasma levels after administration of immediate release dosage forms containing low solubility compounds and after administration of extended release products. Lumenal disintegration times of immediate release dosage forms and the bile acid sequestering activity of resins in the lumen can also be successfully forecasted with biorelevant in vitro testing.

Summary
Biorelevant in-vitro performance testing is an important tool for evaluating intralumenal dosage form performance. Since the formulation of new active pharmaceutical ingredients for oral delivery is more challenging than ever before, efforts to improve the predictability of biorelevant tests are expected to continue.
Total flavonoids of Bidens bipinnata L. a traditional Chinese medicine inhibits the production of inflammatory cytokines of vessel endothelial cells stimulated by sera from Henoch–Schönlein purpura patients
Authors: Bo Yan , Yuan Li-ping , Zhang Jian-jun , Meng Dei-di , Jing Han , Dai Han-jing 
Published: March 2012

Abstract

Objectives
Bidens bipinnata L. is well known as a traditional antipyretic, anti-inflammatory and anti-rheumatic medicine in China. This study was designed to evaluate the role of total extracted flavonoids from B. bipinnata (TFB) in inhibiting the production of inflammatory cytokines.

Methods
Human umbilical vein endothelial cells (HUVEC) were used to examine the effect of TFB on the production of inflammatory cytokines. The supernatant interleukin (IL)-8, tumour necrosis factor (TNF)-α and nitric oxide (NO) levels of HUVEC were measured with ELISA methods. Nuclear factor-kappaB (NF-κB) and fractalkine expression was evaluated by RT-PCR and Western blot methods, respectively.

Key findings
We observed that IL-8, TNF-α and NO release of HUVEC incubated with sera from active Henoch–Schönlein purpura (HSP) was significantly increased. TFB intervention may significantly suppressed the supernatant IL-8, TNF-α and NO levels of HUVEC. Similarly, TFB obviously suppressed the NF-κB and fractalkine mRNA and protein expression.

Conclusions
These results suggested that TFB may be useful for improving microvascular inflammation in HSP patients.
Distinct contributions by ionotropic purinoceptor subtypes to ATP‐evoked calcium signals in mouse parotid acinar cells
Authors: Bhattacharya Sumit , Verrill Douglas S. , Carbone Kristopher M. , Brown Stefanie , Yule David I. , Giovannucci David R. 
Published: March 2012

Key points
There are two major ionotropic purinoceptor subtypes (ATP‐gated, non‐selective, Ca2+‐conducting ion channels) in the salivary gland.
Relatively little is known about the physiological roles of these purinoceptors regarding compartmentalization and selective activation, their contributions to the spatiotemporal properties of intracellular Ca2+ signals and their roles in regulating protein exocytosis and ion channel activity.
In this study, we investigated the subtype‐specific sub‐cellular distribution and functional characterization of purinoceptors in mouse parotid acinar cells.
Selective activation of ionotropic purinergic receptor subtypes was shown to evoke spatially distinct cytosolic Ca2+ signals as well as protein exocytosis.
This study identifies a subtype of ionotropic purinergic receptors as a potential therapeutic target for treatment of salivary gland hypofunction.
Correlative Time-Resolved Fluorescence Microscopy To Assess Antibiotic Diffusion-Reaction in Biofilms
Authors: Daddi Oubekka S. , Briandet R. , Fontaine-Aupart M.-P. , Steenkeste K. 
Published: March 2012

ABSTRACT

The failure of antibiotics to inactivate
in vivo
pathogens organized in biofilms has been shown to trigger chronic infections. In addition to mechanisms involving specific genetic or physiological cell properties, antibiotic sorption and/or reaction with biofilm components may lessen the antibiotic bioavailability and consequently decrease their efficiency. To assess locally and accurately the antibiotic diffusion-reaction, we used for the first time a set of advanced fluorescence microscopic tools (fluorescence recovery after photobleaching, fluorescence correlation spectroscopy, and fluorescence lifetime imaging) that offer a spatiotemporal resolution not available with the commonly used time-lapse confocal imaging method. This set of techniques was used to characterize the dynamics of fluorescently labeled vancomycin in biofilms formed by two
Staphylococcus aureus
human isolates. We demonstrate that, at therapeutic concentrations of vancomycin, the biofilm matrix was not an obstacle to the diffusion-reaction of the antibiotic that can reach all cells through the biostructure.
Multiplex Real-Time PCR for Detection of an Epidemic KPC-Producing Klebsiella pneumoniae ST258 Clone
Authors: Chen Liang , Chavda Kalyan D. , Mediavilla José R. , Zhao Yanan , Fraimow Henry S. , Jenkins Stephen G. , Levi Michael H. , Hong Tao , Rojtman Albert D. , Ginocchio Christine C. , Bonomo Robert A. , Kreiswirth Barry N. 
Published: March 2012

ABSTRACT

We describe a multiplex real-time PCR assay capable of identifying both the epidemic
Klebsiella pneumoniae
ST258 clone and
bla
KPC
carbapenemase genes in a single reaction. The assay displayed excellent sensitivity (100%) and specificity (100%) for identification of ST258 clone and
bla
KPC
in a collection of 75
K. pneumoniae
isolates comprising 41 sequence types. Our results suggest that this assay is an effective tool for surveillance of this clone among carbapenem-resistant
K. pneumoniae
clinical isolates.
Meropenem-Clavulanic Acid Shows Activity against Mycobacterium tuberculosis In Vivo
Authors: England Kathleen , Boshoff Helena I. M. , Arora Kriti , Weiner Danielle , Dayao Emmanuel , Schimel Daniel , Via Laura E. , Barry Clifton E. 
Published: March 2012

ABSTRACT

The carbapenems imipenem and meropenem in combination with clavulanic acid reduced the bacterial burden in
Mycobacterium tuberculosis
-infected macrophages by 2 logs over 6 days. Despite poor stability in solution and a short half-life in rodents, treatment of chronically infected mice revealed significant reductions of bacterial burden in the lungs and spleens. Our results show that meropenem has activity in two
in vivo
systems, but stability and pharmacokinetics of long-term administration will offer significant challenges to clinical evaluation.
Divalent Metals and pH Alter Raltegravir Disposition
In Vitro
Authors: Moss Darren M. , Siccardi Marco , Murphy Matthew , Piperakis Michael M. , Khoo Saye H. , Back David J. , Owen Andrew 
Published: March 2012

ABSTRACT

Raltegravir shows marked pharmacokinetic variability in patients, with gastrointestinal pH and divalent-metal binding being potential factors. We investigated raltegravir solubility, lipophilicity, pK
a
, and permeativity
in vitro
to elucidate known interactions with omeprazole, antacids, and food, all of which increase gastric pH. Solubility of raltegravir was determined at pH 1 to 8. Lipophilicity of raltegravir was determined using octanol-water partition. Raltegravir pK
a
was determined using UV spectroscopy. The effects of pH, metal salts, and omeprazole on the cellular permeativity of raltegravir were determined using Caco-2 monolayers. Cellular accumulation studies were used to determine the effect of interplay between pH and ABCB1 transport on raltegravir accumulation. Samples were analyzed using liquid chromatography-tandem mass spectroscopy (LC-MS/MS) or scintillation counting. Raltegravir at 10 mM was partly insoluble at pH 6.6 and below. Raltegravir lipophilicity was pH dependent and was reduced as pH was increased from 5 to 9. The pK
a
of raltegravir was 6.7. Raltegravir cellular permeativity was heavily influenced by changes in extracellular pH, where apical-to-basolateral permeativity was reduced 9-fold (
P
< 0.05) when apical pH was increased from 5 to 8.5. Raltegravir cellular permeativity was also reduced in the presence of magnesium and calcium. Omeprazole did not alter raltegravir cellular permeativity. Cellular accumulation of raltegravir was increased independently by inhibiting ABCB1 and by lowering extracellular pH from pH 8 to 5. Gastrointestinal pH and polyvalent metals can potentially alter the pharmacokinetic properties of raltegravir, and these data provide an explanation for the variability in raltegravir exposure in patients. The evaluation of how divalent-metal-containing products, such as multivitamins, that do not affect gastric pH alter raltegravir pharmacokinetics in patients is now justified.
Molecular Characterization of Multidrug-Resistant Mycobacterium tuberculosis Isolated in Nepal
Authors: Poudel Ajay , Nakajima Chie , Fukushima Yukari , Suzuki Haruka , Pandey Basu Dev , Maharjan Bhagwan , Suzuki Yasuhiko 
Published: March 2012

ABSTRACTDespite the fact that Nepal is one of the first countries globally to introduce multidrug-resistant tuberculosis (MDR-TB) case management, the number of MDR-TB cases is continuing to rise in Nepal. Rapid molecular tests applicable in this setting to identify resistant organisms would be an effective tool in reversing this trend. To develop such tools, information about the frequency and distribution of mutations that are associated with phenotypic drug resistance inMycobacterium tuberculosisis required. In the present study, we investigated the prevalence of mutations inrpoBandkatGgenes and theinhApromoter region in 158M. tuberculosisisolates (109 phenotypically MDR and 49 non-MDR isolates collected in Nepal) by DNA sequencing. Mutations affecting the 81-bp rifampin (RIF) resistance-determining region (RRDR) ofrpoBwere identified in 106 of 109 (97.3%) RIF-resistant isolates. Codons 531, 526, and 516 were the most commonly affected, at percentages of 58.7, 15.6, and 15.6%, respectively. Of 113 isoniazid (INH)-resistant isolates, 99 (87.6%) had mutations in thekatGgene, with Ser315Thr being the most prevalent (81.4%) substitution. Mutations in theinhApromoter region were detected in 14 (12.4%) INH-resistant isolates. The results from this study provide an overview of the current situation of RIF and INH resistance inM. tuberculosisin Nepal and can serve as a basis for developing or improving rapid molecular tests to monitor drug-resistant strains in this country.
The Type II Secretion System and Its Ubiquitous Lipoprotein Substrate, SslE, Are Required for Biofilm Formation and Virulence of Enteropathogenic Escherichia coli
Authors: Baldi Deborah L. , Higginson Ellen E. , Hocking Dianna M. , Praszkier Judyta , Cavaliere Rosalia , James Catherine E. , Bennett-Wood Vicki , Azzopardi Kristy I. , Turnbull Lynne , Lithgow Trevor , Robins-Browne Roy M. , Whitchurch Cynthia B. , Tauschek Marija 
Published: March 2012

ABSTRACT

Enteropathogenic
Escherichia coli
(EPEC) is a major cause of diarrhea in infants in developing countries. We have identified a functional type II secretion system (T2SS) in EPEC that is homologous to the pathway responsible for the secretion of heat-labile enterotoxin by enterotoxigenic
E. coli
. The wild-type EPEC T2SS was able to secrete a heat-labile enterotoxin reporter, but an isogenic T2SS mutant could not. We showed that the major substrate of the T2SS in EPEC is SslE, an outer membrane lipoprotein (formerly known as YghJ), and that a functional T2SS is essential for biofilm formation by EPEC. T2SS and SslE mutants were arrested at the microcolony stage of biofilm formation, suggesting that the T2SS is involved in the development of mature biofilms and that SslE is a dominant effector of biofilm development. Moreover, the T2SS was required for virulence, as infection of rabbits with a rabbit-specific EPEC strain carrying a mutation in either the T2SS or SslE resulted in significantly reduced intestinal colonization and milder disease.