bluuebunny/crossref_metadata_2025 huggingface dataset:
Glutamate Receptor Antagonists as Fast-Acting Therapeutic Alternatives for the Treatment of Depression: Ketamine and Other Compounds
Authors: Niciu Mark J. , Henter Ioline D. , Luckenbaugh David A. , Zarate Carlos A. , Charney Dennis S.
Published: January 2014

The N-methyl-d-aspartate (NMDA) receptor antagonist ketamine has rapid and potent antidepressant effects in treatment-resistant major depressive disorder and bipolar depression. These effects are in direct contrast to the more modest effects seen after weeks of treatment with classic monoaminergic antidepressants. Numerous open-label and case studies similarly validate ketamine's antidepressant properties. These clinical findings have been reverse-translated into preclinical models in an effort to elucidate ketamine's antidepressant mechanism of action, and three important targets have been identified: mammalian target of rapamycin (mTOR), eukaryotic elongation factor 2 (eEF2), and glycogen synthase kinase-3 (GSK-3). Current clinical and preclinical research is focused on (a) prolonging/maintaining ketamine's antidepressant effects, (b) developing more selective NMDA receptor antagonists free of ketamine's adverse effects, and (c) identifying predictor, mediator/moderator, and treatment response biomarkers of ketamine's antidepressant effects.
A Reevaluation of CD22 Expression in Human Lung Cancer
Authors: Pop Laurentiu M. , Barman Stephen , Shao Chunli , Poe Jonathan C. , Venturi Guglielmo M. , Shelton John M. , Pop Iliodora V. , Gerber David E. , Girard Luc , Liu Xiao-yun , Behrens Carmen , Rodriguez-Canales Jaime , Liu Hui , Wistuba Ignacio I. , Richardson James A. , Minna John D. , Tedder Thomas F. , Vitetta Ellen S.
Published: January 2014

CD22 is a transmembrane glycoprotein expressed by mature B cells. It inhibits signal transduction by the B-cell receptor and its coreceptor CD19. Recent reports indicate that most human lung cancer cells and cell lines express CD22, making it an important new therapeutic target for lung cancer. The objective of our studies was to independently validate these results with the goal of testing the efficacy of our CD22 immunotoxins on lung cancer cell lines. As determined by quantitative real-time PCR analysis, we found that levels of CD22 mRNA in a panel of human lung cancer cell lines were 200 to 60,000-fold lower than those observed in the human CD22+ Burkitt lymphoma cells, Daudi. Using flow cytometry with a panel of CD22 monoclonal antibodies and Western blot analyses, we could not detect surface or intracellular expression of CD22 protein in a panel of lung cancer cell lines. In addition, the in vitro proliferation of the lung tumor cell lines was not affected by either CD22 antibodies or our highly potent anti-CD22 immunotoxin. In contrast, CD22+ Daudi cells expressed high levels of CD22 mRNA and protein, and were sensitive to our CD22 immunotoxin. Importantly, primary non–small cell lung cancers from more than 250 patient specimens did not express detectable levels of CD22 protein as assessed by immunohistochemistry. We conclude that CD22 is not expressed at measurable levels on the surface of lung cancer cells, and that these cells cannot be killed by anti-CD22 immunotoxins. Cancer Res; 74(1); 263–71. ©2014 AACR.
Transcriptional Profiling of Melanoma Sentinel Nodes Identify Patients with Poor Outcome and Reveal an Association of CD30+ T Lymphocytes with Progression
Authors: Vallacchi Viviana , Vergani Elisabetta , Camisaschi Chiara , Deho Paola , Cabras Antonello D. , Sensi Marialuisa , De Cecco Loris , Bassani Niccolò , Ambrogi Federico , Carbone Antonino , Crippa Federica , Vergani Barbara , Frati Paola , Arienti Flavio , Patuzzo Roberto , Villa Antonello , Biganzoli Elia , Canevari Silvana , Santinami Mario , Castelli Chiara , Rivoltini Licia , Rodolfo Monica
Published: January 2014

Sentinel lymph nodes set the stance of the immune system to a localized tumor and are often the first site to be colonized by neoplastic cells that metastasize. To investigate how the presence of neoplastic cells in sentinel lymph nodes may trigger pathways associated with metastatic progression, we analyzed the transcriptional profiles of archival sentinel node biopsy specimens obtained from melanoma patients. Biopsies from positive nodes were selected for comparable tumor infiltration, presence or absence of further regional node metastases, and relapse at 5-year follow-up. Unsupervised analysis of gene expression profiles revealed immune response to be a major gene ontogeny represented. Among genes upregulated in patients with progressing disease, the TNF receptor family member CD30/TNFRSF8 was confirmed in biopsy specimens from an independent group of patients. Immunohistochemical analysis revealed higher numbers of CD30+ lymphocytes in nodes from progressing patients compared with nonprogressing patients. Phenotypic profiling demonstrated that CD30+ lymphocytes comprised a broad population of suppressive or exhausted immune cells, such as CD4+Foxp3+ or PD1+ subpopulations and CD4−CD8− T cells. CD30+ T lymphocytes were increased in peripheral blood lymphocytes of melanoma patients at advanced disease stages. Our findings reinforce the concept that sentinel nodes act as pivotal sites for determining progression patterns, revealing that the presence of CD30+ lymphocytes at those sites associate positively with melanoma progression. Cancer Res; 74(1); 130–40. ©2014 AACR.
Global Environmental Law and Treaty-Making on Hazardous Substances: The Minamata Convention and Mercury Abatement
Authors: Selin Henrik
Published: January 2014

In global environmental cooperation, legally binding agreements remain a customary way for states to set common goals and standards. This article analyzes the Minamata Convention on Mercury by addressing three questions: First, how did linkages to earlier agreements shape the negotiations? Second, what were the main legal and political issues during the negotiations? Third, what are the major issues moving forward with treaty implementation and mercury abatement? The analysis shows that the decision to start treaty negotiations was influenced by related policy developments on hazardous chemicals as well as differences in national interests. Five sets of issues dominated the negotiations: 1) supply and trade, 2) products and processes, 3) emissions and releases, 4) artisanal and small-scale gold mining, and 5) resources and compliance. The article concludes that future mercury abatement hinges on the parties' ability to move beyond the initial mandates, as the convention may affect decisions by a wide range of public, private, and civil society actors.
Cross-National Public Opinion on Climate Change: The Effects of Affluence and Vulnerability
Authors: Kim So Young , Wolinsky-Nahmias Yael
Published: January 2014

Climate change has emerged as one of the most important issues of the twentyfirst century. Recent opinion polls show rising public awareness of climate change. Yet considerable cross-national variation exists in the intensity of public concern and in public willingness to pay for addressing climate change. Drawing on twelve multinational surveys, we examine two aggregate conditions—a country's affluence and its vulnerability to climate risks—as key factors underlying cross-national differences in public support for and commitment to costly climate policies. In contrast to the post-materialism thesis, we find “strong” concern about climate change to be higher in developing countries. Contrary to expectation, climate vulnerability had little effect on public concern, but did have significant impact on some measures of personal commitment and support for climate policies. The analysis indicates that, in most countries examined, high concern about climate change is only beginning to translate into personal commitment to action.
Impact of Orbitofrontal Lesions on Electrophysiological Signals in a Stop Signal Task
Authors: Solbakk Anne-Kristin , Funderud Ingrid , Løvstad Marianne , Endestad Tor , Meling Torstein , Lindgren Magnus , Knight Robert T. , Krämer Ulrike M.
Published: January 2014

Behavioral inhibition and performance monitoring are critical cognitive functions supported by distributed neural networks including the pFC. We examined neurophysiological correlates of motor response inhibition and action monitoring in patients with focal orbitofrontal (OFC) lesions (n = 12) after resection of a primary intracranial tumor or contusion because of traumatic brain injury. Healthy participants served as controls (n = 14). Participants performed a visual stop signal task. We analyzed behavioral performance as well as event-related brain potentials and oscillations. Inhibition difficulty was adjusted individually to yield an equal amount of successful inhibitions across participants. RTs of patients and controls did not differ significantly in go trials or in failed stop trials, and no differences were observed in estimated stop signal RT. However, electrophysiological response patterns during task performance distinguished the groups. Patients with OFC lesions had enhanced P3 amplitudes to congruent condition go signals and to stop signals. In stop trials, patients had attenuated N2 and error-related negativity, but enhanced error positivity. Patients also showed enhanced and prolonged post-error beta band increases for stop errors. This effect was particularly evident in patients whose lesion extended to the subgenual cingulate cortex. In summary, although response inhibition was not impaired, the diminished stop N2 and ERN support a critical role of the OFC in action monitoring. Moreover, the increased stop P3, error positivity, and post-error beta response indicate that OFC injury affected action outcome evaluation and support the notion that the OFC is relevant for the processing of abstract reinforcers such as performing correctly in the task.
Prior Expectations Evoke Stimulus Templates in the Primary Visual Cortex
Authors: Kok Peter , Failing Michel F. , de Lange Floris P.
Published: January 2014

Sensory processing is strongly influenced by prior expectations. Valid expectations have been shown to lead to improvements in perception as well as in the quality of sensory representations in primary visual cortex. However, very little is known about the neural correlates of the expectations themselves. Previous studies have demonstrated increased activity in sensory cortex following the omission of an expected stimulus, yet it is unclear whether this increased activity constitutes a general surprise signal or rather has representational content. One intriguing possibility is that top–down expectation leads to the formation of a template of the expected stimulus in visual cortex, which can then be compared with subsequent bottom–up input. To test this hypothesis, we used fMRI to noninvasively measure neural activity patterns in early visual cortex of human participants during expected but omitted visual stimuli. Our results show that prior expectation of a specific visual stimulus evokes a feature-specific pattern of activity in the primary visual cortex (V1) similar to that evoked by the corresponding actual stimulus. These results are in line with the notion that prior expectation triggers the formation of specific stimulus templates to efficiently process expected sensory inputs.
Different Neural Networks Are Involved in Audiovisual Speech Perception Depending on the Context
Authors: Malfait Nicole , Fonlupt Pierre , Centelles Laurie , Nazarian Bruno , Brown Liana E. , Caclin Anne
Published: January 2014

How are we able to easily and accurately recognize speech sounds despite the lack of acoustic invariance? One proposed solution is the existence of a neural representation of speech syllable perception that transcends its sensory properties. In the present fMRI study, we used two different audiovisual speech contexts both intended to identify brain areas whose levels of activation would be conditioned by the speech percept independent from its sensory source information. We exploited McGurk audiovisual fusion to obtain short oddball sequences of syllables that were either (a) acoustically different but perceived as similar or (b) acoustically identical but perceived as different. We reasoned that, if there is a single network of brain areas representing abstract speech perception, this network would show a reduction of activity when presented with syllables that are acoustically different but perceived as similar and an increase in activity when presented with syllables that are acoustically similar but perceived as distinct. Consistent with the long-standing idea that speech production areas may be involved in speech perception, we found that frontal areas were part of the neural network that showed reduced activity for sequences of perceptually similar syllables. Another network was revealed, however, when focusing on areas that exhibited increased activity for perceptually different but acoustically identical syllables. This alternative network included auditory areas but no left frontal activations. In addition, our findings point to the importance of subcortical structures much less often considered when addressing issues pertaining to perceptual representations.
A method to aid in the interpretation of EFA results: An application of Pratt’s measures
Authors: Wu Amery D. , Zumbo Bruno D. , Marshall Sheila K.
Published: January 2014

This article describes a method based on Pratt’s measures and demonstrates its use in exploratory factor analyses. The article discusses the interpretational complexities due to factor correlations and how Pratt’s measures resolve these interpretational problems. Two real data examples demonstrate the calculation of what we call the “D matrix,” of which the elements are Pratt’s measures. Focusing on the rows of the D matrix allows one to compare the importance of the factors to the communality of each observed indicator ( horizontal interpretation); whereas a focus on the columns of the D matrix allows one to compare the contribution of the indicators to the common variance extracted by each factor ( vertical interpretation). The application showed that the method based on Pratt’s measures is a very simple but useful technique for EFA, in particular, for behavioral and developmental constructs, which are often multidimensional and mutually correlated.
Mothers’ appraisal of goodness of fit and children’s social development
Authors: Seifer Ronald , Dickstein Susan , Parade Stephanie , Hayden Lisa C. , Magee Karin Dodge , Schiller Masha
Published: January 2014

Goodness of fit has been a key theoretical construct for understanding caregiver–child relationships. We developed an interview method to assess goodness of fit as a relationship construct, and employed this method in a longitudinal study of child temperament, family context, and attachment relationship formation. Goodness of fit at 4 and 8 months of age predicted secure attachment at 15 months, after accounting for variance associated with SES, maternal depression, child temperament, parenting quality, and family functioning. Structural models indicated that prediction of security by goodness of fit and parenting quality was relatively independent. The goodness-of-fit pathway was most associated with maternal depression, whereas the parenting sensitivity pathway was most associated with child temperament, family functioning, and SES.
Pharmacoeconomic Analysis of the Diabetes Initiative Program
Authors: Franklin Brandi E. , Farland Michelle Z. , Thomas Jeremy , McFarland M. Shawn , Ray Shaunta’ M. , Byrd Debbie C.
Published: January 2014

Background: Diabetes treatment cost increased 41% from 2007 to 2011. Pharmacists have provided collaborative diabetes management for decades with improvement in disease-related end points. Few have reported economic benefits of pharmacist management of type 2 diabetes. Objective: The purpose was to determine if cost savings associated with hemoglobin A1c (A1C) and systolic blood pressure (SBP) change outweighed programmatic pharmacist-physician collaborative care model costs. Methods: This cost analysis of a 12 month, prospective, multicenter, observational study included English-speaking adults, 18 years or older, with type 2 diabetes mellitus, a life expectancy >1 year, and either a A1C >7%, SBP >130 mm Hg, diastolic blood pressure >80 mm Hg, or low-density lipoprotein concentration >100 mg/dL. Pregnant patients were excluded. Primary analysis outcome was average cost per outcome, ratio of net cost (numerator) and percentage achieving outcomes (denominator). Assessment outcomes included A1C reduction by at least 1% and SBP reduction by at least 5.6 mm Hg. Results: 206 patients were seen by pharmacists during 1612 encounters (mean = 7.8 encounters/patient). Pharmacists spent 983 hours caring for type 2 diabetes patients (mean 3.8 hours/patient). Base case net labor and program costs per patient were −$66.77 and $106.81, respectively. Improvement in A1C and SBP yielded $421.01 in cost savings per patient. Labor and program average costs per patient for each outcome achieved were −$100.40 and $160.61, respectively. Conclusions: This multisite pharmacist-physician collaboration in diabetes management showed cost savings when assessing pharmacist labor costs alone. Total program costs, including overhead, slightly increased cost of care.
Acute Hepatitis and Renal Failure Related to Intranasal Buprenorphine Misuse
Authors: Eiden Céline , Ripault Marie-Pierre , Larrey Dominique , Faillie Jean-Luc , Pinzani Véronique , Pageaux Georges-Philippe , Peyrière Hélène
Published: January 2014

Background: Rare cases of acute hepatitis have been reported following injection, overdose, and even during the use of buprenorphine (BPN) at therapeutic doses, especially in carriers of hepatitis C virus (HCV). Objectives: To report a case of acute hepatitis and renal failure related to intranasal BPN misuse in a HCV-negative patient and to analyze cases reported to the French postmarketing surveillance system (PMSS) of drugs and in the literature. Methods: All cases of hepatitis related to BPN reported to PMSS between January 1996 and December 2012 were analyzed. Results: A 42-year-old man with a history of intranasal BPN misuse (8 mg/d) for at least 10 years was admitted for flu-like symptoms and abdominal pain. At admission, the patient consumed alcohol, cannabis, and tobacco. Acute hepatitis and acute renal failure were diagnosed . Clinical signs and biological parameters resolved within 26 days. An objective causality assessment revealed that an adverse drug reaction (ADR) was possible. In the French PMSS database, 41 cases of suspected BPN-induced hepatitis are reported. In 36.6% of cases, BPN was misused by the intravenous route. In the literature, 16 cases of acute hepatitis related to BPN with or without renal failure are reported. In all cases, patients were HCV carriers. The primary mechanism of BPN-induced hepatitis is a mitochondrial dysfunction, exacerbated by cofactors (HCV, alcohol, and medications). Conclusion: Intranasal misuse of BPN is increasingly frequent. We report here the first documented case of acute hepatitis and renal failure related to intranasal BPN misuse in a patient negative for HCV infection.
Use of Daptomycin to Treat Infections With Methicillin-Resistant Staphylococcus aureus Isolates Having Vancomycin Minimum Inhibitory Concentrations of 1.5 to 2 µg/mL
Authors: McDaneld Patrick M. , Spooner Linda M. , Mohr John F. , Belliveau Paul P.
Published: January 2014

Objective: To evaluate daptomycin use for the treatment of infections with methicillin-resistant Staphylococcus aureus (MRSA) isolates having vancomycin minimum inhibitory concentrations (MICs) of 1.5 to 2 µg/mL. Data Sources: The literature was retrieved through PubMed and EMBASE (January 2006 to August 2013).Study Selection and Data Extraction: English articles were reviewed. Studies that included separate daptomycin data (clinical outcome or in vitro surveillance) for MRSA isolates with vancomycin MICs of 1.5 to 2 µg/mL by any testing methodology were included. Data Synthesis: Clinical and microbiological outcomes associated with daptomycin used as first-line or subsequent therapy for MRSA infections with vancomycin MICs of 1.5 to 2 µg/mL were reported in 7 retrospective clinical studies; susceptibility information involving such isolates was reported from 12 surveillancestudies. Although not all studies demonstrated outcome differences between daptomycin and comparator treatments (usually vancomycin), when differences were reported, they were in favor of daptomycin. Individual studies found lower 60-day (8% vs 20%, P = .046) and 30-day mortality (3.5% vs 12.9%, P = .047) and increased treatment success with daptomycin (68.6% vs 43.1%, P = .008; 76.9% vs 53.8%, P = .048) in bacteremic patients. The median doses used for treatment of bacteremia were greater than that approved by the FDA for this indication (6 mg/kg/d). Conclusions: Current published evidence indicates daptomycin may be an acceptable alternative to vancomycin for MRSA infections, especially bacteremia, involving isolates with vancomycin MIC values of 1.5 to 2 µg/mL. Additional evidence is needed to fully elucidate daptomycin utility in this area.
Evaluation of Pharmacist-Managed Dabigatran in an Inpatient Setting
Authors: Tedders Kristen M. , Lucey Michael F. , Edwin Stephanie B.
Published: January 2014

Background: Although therapeutic drug monitoring is not required for patients receiving dabigatran to determine therapeutic efficacy, there are a number of other factors to consider. Currently, there are no studies evaluating pharmacist-led management of dabigatran. Objective: The role of inpatient pharmacists related to the management of dabigatran was evaluated. Methods: All adult patients who received at least 1 dose of dabigatran with a length of stay greater than 24 hours in a single-center, community hospital between May 2011 and August 2012 were retrospectively reviewed (n = 176). Results: Almost half of the patients (46%) required pharmacist intervention related to dabigatran management during hospital admission. Of patients receiving dabigatran prior to hospital admission, 18.4% were admitted on an inappropriate home dose. Transitioning between dabigatran and alternative anticoagulants accounted for the majority of pharmacist interventions (74.2%), with patients transitioning from unfractionated heparin to dabigatran occurring most frequently. Renal impairment requiring dose adjustment or drug discontinuation occurred in 6.3% of patients, whereas 6.8% of patients required pharmacist intervention for procedural anticoagulation. Inpatient therapy was determined to be relatively safe, with few patients (1.7%) requiring permanent discontinuation of dabigatran as a result of a bleeding complication. Conclusion: Pharmacists significantly contributed to the safe and appropriate use of dabigatran during hospitalization.
Varenicline-Induced Coronary Thrombosis
Authors: Kalaycı Arzu , Eren Aysegul , Kocabay Gonenc , Karabay Can Yucel , Gecmen Cetin , Kırma Cevat
Published: January 2014

Varenicline (Champix, Chantix) has been available for use in smoking cessation since 2006. This drug has been associated with adverse cardiovascular events. Potential mechanisms for this association include modulation of parasymphathetic output from the brainstem to the heart, release of catecholamines and prothrombotic effect. We report the case of a 30-year-old man with no known cardiac disease, who developed thrombotic occlusion of left anterior descending artery and presented with acute coronary syndrome secondary to treatment with varenicline. The Naranjo probability scale indicates that varenicline was the probable cause of the myocardial infarction.
c-Myc inhibition prevents leukemia initiation in mice and impairs the growth of relapsed and induction failure pediatric T-ALL cells
Authors: Roderick Justine E. , Tesell Jessica , Shultz Leonard D. , Brehm Michael A. , Greiner Dale L. , Harris Marian H. , Silverman Lewis B. , Sallan Stephen E. , Gutierrez Alejandro , Look A. Thomas , Qi Jun , Bradner James E. , Kelliher Michelle A.
Published: January 2014

Key Points

c-Myc is required for leukemia-initiating cell maintenance in murine models of T-ALL. c-Myc inhibition prevents the growth of treatment-resistant primary T-ALL patient samples in vitro.
The epidemiology of hospital treated traumatic brain injury in Scotland
Authors: Shivaji Tara , Lee Andrew , Dougall Nadine , McMillan Thomas , Stark Cameron
Published: January 2014

Background

Traumatic Brain Injury (TBI) is an important global public health problem made all the more important by the increased likelihood of disability following a hospital admission for TBI. Understanding those groups most at risk will help inform interventions designed to prevent causes of TBI, such as falls prevention measures. This study identifies the rate of hospitalisation episodes of TBI in Scotland, explores causes of TBI admissions, and trends in hospitalisation episodes by age and gender over a twelve year period using routinely collected hospital data.

Methods

A retrospective analysis of routine hospital episode data identified records relating to TBI for the twelve years between 1998 and 2009. Descriptive and joinpoint regression analysis were used, average annual percentage changes (AAPC) and annual percentage change (APC) in rates were calculated.

Results

Between 1998 and 2009 there were 208,195 recorded episodes of continuous hospital care in Scotland as a result of TBI. Almost half (47%) of all TBIs were the result of falls, with marked peaks observed in the very young and the oldest groups. The AAPC of hospitalization episode rates over the study period for boys and girls aged 0-14 were -4.9% (95% CI -3.5 to-6.3) and -4.7% (95% CI -2.6 to -6.8) respectively. This reduction was not observed in older age groups. In women aged 65 and over there was an APC of 3.9% (95% CI 1.2 to 6.6) between 2004 and 2009.

Conclusions

Hospitalisation for TBI is relatively common in Scotland. The rise in the age-adjusted rate of hospitalisation episodes observed in older people indicates that reduction of TBI should be a public health priority in countries with an ageing population. Public health interventions such as falls prevention measures are well advised and evaluations of such interventions should consider including TBI hospitalisation as an alternative or supplementary outcome measure to fractured neck of femur. Further research is needed to advance understanding of the associations of risk factors with increased incidence of TBI hospital episodes in the elderly population.
Overexpression of phosphatidylinositol 4-kinase type IIIα is associated with undifferentiated status and poor prognosis of human hepatocellular carcinoma
Authors: Ilboudo Adeodat , Nault Jean-Charles , Dubois-Pot-Schneider Hélène , Corlu Anne , Zucman-Rossi Jessica , Samson Michel , Le Seyec Jacques
Published: January 2014

Background

Hepatocellular carcinoma (HCC) is a particularly severe disease characterized by a high rate of recurrence and death even after surgical resection. Molecular characterization of HCC helps refine prognosis and may facilitate the development of improved therapy. Phosphatidylinositol 4-kinases have recently been identified as cellular factors associated with cancer. Also, phosphatidylinositol 4-kinase type IIIα (PI4KA) is necessary for the propagation of the hepatitis C virus, a major etiological factor for HCC.

Methods

Reverse transcription, quantitative real-time PCR was used to assay PI4KA mRNA. The expression levels were investigated both in a collection of molecularly and clinically characterized hepatic tissues from 344 patients with diverse liver diseases and in human hepatocyte cell lines whose proliferative and differentiation status was controlled by specific culture conditions. Analytical microarray data for 60 HCC and six normal liver tissue samples were exploited to study correlations between PI4KA mRNA levels and cell proliferation markers in vivo. Postoperative disease-specific survival and time to recurrence in a set of 214 patients with HCC were studied by univariate and multivariate analyses.

Results

PI4KA mRNA was more abundant in HCC than normal healthy tissues. This upregulation correlated significantly with both poor differentiation and the active proliferation rate in HCC. These associations were confirmed with in vitro models. Moreover, patients with HCC who had been treated by surgical resection and had higher PI4KA mRNA concentrations in their tumor tissue exhibited a higher risk of tumor recurrence (median time: 20 months versus 49 months, P = 0.0012) and shorter disease-specific survival (first quartile time: 16 months versus 48 months, P = 0.0004). Finally, the abundance of PI4KA mRNA proved to be an independent prognostic marker of survival for cases of HCC (hazard ratio = 2.36, P = 0.0064).

Conclusions

PI4KA mRNA could be used as a new molecular marker to improve established prognostic models for HCC. These findings also indicate possible new lines of research for the development of innovative therapeutic approaches targeting PI4KA.
Lymph node fine needle Cytology in the staging and follow-up of Cutaneous Lymphomas
Authors: Vigliar Elena , Cozzolino Immacolata , Picardi Marco , Peluso Anna Lucia , Fernandez Laura Virginia Sosa , Vetrani Antonio , Botti Gerardo , Pane Fabrizio , Selleri Carmine , Zeppa Pio
Published: January 2014

Background

Lymph nodal involvement is an important clinical-pathological sign in primary cutaneous lymphoma (PCL), as it marks the transformation/evolution of the disease from localized to systemic; therefore the surveillance of lymph nodes is important in the staging and follow up of PCL. Fine needle cytology (FNC) is widely used in the diagnosis of lymphadenopathies but has rarely been reported in PCL staging and follow-up. In this study an experience on reactive and neoplastic lymphadenopathies arisen in PCL and investigated by FNC, combined to ancillary techniques, is reported.

Methods

Twenty-one lymph node FNC from as many PCL patients were retrieved; 17 patients had mycosis fungoides (MF) and 4 a primary cutaneous B-cell lymphoma (PBL). In all cases, rapid on site evaluation (ROSE) was performed and additional passes were used to perform flow cytometry (FC), immunocytochemistry (ICC) and/or polymerase chain reaction (PCR) to assess or rule out a possible clonality of the corresponding cell populations.

Results

FNC combined with FC, ICC, and PCR identified 12 cases of reactive, non specific, hyperplasia (BRH), 4 dermatopathic lymphadenopathy (DL), 4 lymph nodal involvement by MF and 1 lymph nodal involvement by cutaneous B-cell lymphoma.

Conclusions

FNC coupled with ancillary techniques is an effective tool to evaluate lymph node status in PCL patients, provided that ROSE and a rational usage of ancillary techniques is performed according to the clinical context and the available material. The method can be reasonably used as first line procedure in PCL staging and follow up, avoiding expensive and often ill tolerated biopsies when not strictly needed.
Discovery of potential anti-infectives against Staphylococcus aureus using a Caenorhabditis elegans infection model
Authors: Kong Cin , Yehye Wageeh A , Abd Rahman Noorsaadah , Tan Man-Wah , Nathan Sheila
Published: January 2014

Background

The limited antibiotic options for effective control of methicillin-resistant Staphylococcus aureus infections has led to calls for new therapeutic approaches to combat this human pathogen. An alternative approach to control MRSA is through the use of anti-infective agents that selectively disrupt virulence-mediated pathways without affecting microbial cell viability or by modulating the host natural immune defenses to combat the pathogen.

Methods

We established a C. elegans – S. aureus liquid-based assay to screen for potential anti-infectives against S. aureus. The assay was utilized to screen 37 natural extracts and 29 synthetic compounds for the ability to extend the lifespan of infected nematodes. Disc diffusion and MIC microdilution tests were used to evaluate the anti-microbial properties of these natural extracts and synthetic compounds whilst in vivo bacterial CFU within the C. elegans gut were also enumerated.

Results

We screened a total of 37 natural extracts and 29 synthetic compounds for anti-infective properties. The screen successfully revealed 14 natural extracts from six plants (Nypa fruticans, Swietenia macrophylla, Curcuma longa, Eurycoma longifolia, Orthosiphon stamineus and Silybum eburneum) and one marine sample (Faunus ater) that improved the survival of S. aureus-infected worms by at least 2.8-fold as well as 14 synthetic compounds that prolonged the survival of S. aureus-infected nematodes by 4-fold or greater. An anti-microbial screen of all positive hits demonstrated that 8/28 hits had no effect on S. aureus growth. Of these 8 candidates, 5 of them also protected the worms from MRSA infection. We also noted that worms exposed to N. fruticans root and O. stamineus leaf extracts showed reduced intestinal colonization by live S. aureus. This suggests that these extracts could possibly activate host immunity to eliminate the bacteria or interfere with factor/s that prevents pathogen accumulation.

Conclusion

We have successfully demonstrated the utility of this liquid-based screen to identify anti-infective substances that prolong S. aureus- infected host survival without affecting bacterial cell viability.
Community-based health care for indigenous women in Mexico: a qualitative evaluation
Authors: Pelcastre-Villafuerte Blanca , Ruiz Myriam , Meneses Sergio , Amaya Claudia , Márquez Margarita , Taboada Arianna , Careaga Katherine
Published: January 2014

Introduction

Indigenous women in Mexico represent a vulnerable population in which three kinds of discrimination converge (ethnicity, gender and class), having direct repercussions on health status. The discrimination and inequity in health care settings brought this population to the fore as a priority group for institutional action. The objective of this study was to evaluate the processes and performance of the “Casa de la Mujer Indígena”, a community based project for culturally and linguistically appropriate service delivery for indigenous women. The evaluation summarizes perspectives from diverse stakeholders involved in the implementation of the model, including users, local authorities, and institutional representatives.

Methods

The study covered five Casas implementation sites located in four Mexican states. A qualitative process evaluation focused on systematically analyzing the Casas project processes and performance was conducted using archival information and semi-structured interviews. Sixty-two interviews were conducted, and grounded theory approach was applied for data analysis.

Results

Few similarities were observed between the proposed model of service delivery and its implementation in diverse locations, signaling discordant operating processes. Evidence gathered from Casas personnel highlighted their ability to detect obstetric emergencies and domestic violence cases, as well as contribute to the empowerment of women in the indigenous communities served by the project. These themes directly translated to increases in the reporting of abuse and referrals for obstetric emergencies.

Conclusions

The model’s cultural and linguistic competency, and contributions to increased referrals for obstetric emergencies and abuse are notable successes. The flexibility and community-based nature of the model has allowed it to be adapted to the particularities of diverse indigenous contexts. Local, culturally appropriate implementation has been facilitated by the fact that the Casas have been implemented with local leadership and local women have taken ownership. Users express overall satisfaction with service delivery, while providing constructive feedback for the improvement of existing Casas, as well as more cost-effective implementation of the model in new sites. Integration of user’s input obtained from this process evaluation into future planning will undoubtedly increase buy-in. The Casas model is pertinent and viable to other contexts where indigenous women experience disparities in care.
ZNF300P1 Encodes a lincRNA that regulates cell polarity and is epigenetically silenced in type II epithelial ovarian cancer
Authors: Gloss Brian , Moran-Jones Kim , Lin Vita , Gonzalez Maria , Scurry James , Hacker Neville F , Sutherland Robert L , Clark Susan J , Samimi Goli
Published: January 2014

Background

We previously identified that the CpG island-associated promoter of the novel lincRNA ZNF300P1 (also known as LOC134466) is frequently hypermethylated and silenced in ovarian cancer tissues. However, the function of ZNF300P1 was unknown. In this report we demonstrate that ZNF300P1 is involved in the regulation of key cell cycle and cell motility networks in human ovarian surface epithelial cells, and may play a role in promoting metastasis in ovarian cancer cells.

Methods

We applied methylated DNA immunoprecipitation on whole genome promoter tiling arrays and Sequenom assays to examine methylation status of ZNF300P1 in multiple ovarian cancer cell lines, as well as in normal ovarian and ovarian tumor tissues. Transcript profiling was used to investigate the effects of ZNF300P1 suppression in ovarian cancer cells. We utilized siRNA knockdown in normal ovarian surface epithelial cells and performed cellular proliferation, migration and adhesion assays to validate and explore the profiling results.

Results

We demonstrate that ZNF300P1 is methylated in multiple ovarian cancer cell lines. Loss of ZNF300P1 results in decreased cell proliferation and colony formation. In addition, knockdown of the ZNF300P1 transcript results in aberrant and less persistent migration in wound healing assays due to a loss of cellular polarity. Using an ex vivo peritoneal adhesion assay, we also reveal a role for ZNF300P1 in the attachment of ovarian cancer cells to peritoneal membranes, indicating a potential function of ZNF300P1 expression in metastasis of ovarian cancer cells to sites within the peritoneal cavity.

Conclusion

Our findings further support ZNF300P1 as frequently methylated in ovarian cancer and reveal a novel function for ZNF300P1 lincRNA expression in regulating cell polarity, motility, and adhesion and loss of expression may contribute to the metastatic potential of ovarian cancer cells.
Resistivity dependence of magnetoresistance in Co/ZnO films
Authors: Quan Zhi-Yong , Zhang Li , Liu Wei , Zeng Hao , Xu Xiao-Hong
Published: January 2014

We report the dependence of magnetoresistance effect on resistivity (ρ) in Co/ZnO films deposited by magnetron sputtering at different sputtering pressures with different ZnO contents. The magnitude of the resistivity reflects different carrier transport regimes ranging from metallic to hopping behaviors. Large room-temperature magnetoresistance greater than 8% is obtained in the resistivity range from 0.08 to 0.5 Ω · cm. The magnetoresistance value decreases markedly when the resistivity of the films is less than 0.08 Ω · cm or greater than 0.5 Ω · cm. When 0.08 Ω · cm < ρ < 0.5 Ω · cm, the conduction contains two channels: the spin-dependent tunneling channel and the spin-independent second-order hopping (N = 2). The former gives rise to a high room-temperature magnetoresistance effect. When ρ > 0.5 Ω · cm, the spin-independent higher-order hopping (N > 2) comes into play and decreases the tunneling magnetoresistance value. For the samples with ρ < 0.08 Ω · cm, reduced magnetoresistance is mainly ascribed to the formation of percolation paths through interconnected elongated metallic Co particles. This observation is significant for the improvement of room-temperature magnetoresistance value for future spintronic devices.
Enhanced optical output power of blue light-emitting diodes with quasi-aligned gold nanoparticles
Authors: Jin Yuanhao , Li Qunqing , Li Guanhong , Chen Mo , Liu Junku , Zou Yuan , Jiang Kaili , Fan Shoushan
Published: January 2014

The output power of the light from GaN-based light-emitting diodes (LEDs) was enhanced by fabricating gold (Au) nanoparticles on the surface of p-GaN. Quasi-aligned Au nanoparticle arrays were prepared by depositing Au thin film on an aligned suspended carbon nanotube thin film surface and then putting the Au-CNT system on the surface of p-GaN and thermally annealing the sample. The size and position of the Au nanoparticles were confined by the carbon nanotube framework, and no other additional residual Au was distributed on the surface of the p-GaN substrate. The output power of the light from the LEDs with Au nanoparticles was enhanced by 55.3% for an injected current of 100 mA with the electrical property unchanged compared with the conventional planar LEDs. The enhancement may originate from the surface plasmon effect and scattering effect of the Au nanoparticles.
Differential proteomic analysis of synovial fluid from rheumatoid arthritis and osteoarthritis patients
Authors: Balakrishnan Lavanya , Bhattacharjee Mitali , Ahmad Sartaj , Nirujogi Raja Sekhar , Renuse Santosh , Subbannayya Yashwanth , Marimuthu Arivusudar , Srikanth Srinivas M , Raju Rajesh , Dhillon Mukesh , Kaur Navjyot , Jois Ramesh , Vasudev Vivek , Ramachandra YL , Sahasrabuddhe Nandini A , Prasad TS Keshava , Mohan Sujatha , Gowda Harsha , Shankar Subramanian , Pandey Akhilesh
Published: January 2014

Background

Rheumatoid arthritis and osteoarthritis are two common musculoskeletal disorders that affect the joints. Despite high prevalence rates, etiological factors involved in these disorders remain largely unknown. Dissecting the molecular aspects of these disorders will significantly contribute to improving their diagnosis and clinical management. In order to identify proteins that are differentially expressed between these two conditions, a quantitative proteomic profiling of synovial fluid obtained from rheumatoid arthritis and osteoarthritis patients was carried out by using iTRAQ labeling followed by high resolution mass spectrometry analysis.

Results

We have identified 575 proteins out of which 135 proteins were found to be differentially expressed by ≥3-fold in the synovial fluid of rheumatoid arthritis and osteoarthritis patients. Proteins not previously reported to be associated with rheumatoid arthritis including, coronin-1A (CORO1A), fibrinogen like-2 (FGL2), and macrophage capping protein (CAPG) were found to be upregulated in rheumatoid arthritis. Proteins such as CD5 molecule-like protein (CD5L), soluble scavenger receptor cysteine-rich domain-containing protein (SSC5D), and TTK protein kinase (TTK) were found to be upregulated in the synovial fluid of osteoarthritis patients. We confirmed the upregulation of CAPG in rheumatoid arthritis synovial fluid by multiple reaction monitoring assay as well as by Western blot. Pathway analysis of differentially expressed proteins revealed a significant enrichment of genes involved in glycolytic pathway in rheumatoid arthritis.

Conclusions

We report here the largest identification of proteins from the synovial fluid of rheumatoid arthritis and osteoarthritis patients using a quantitative proteomics approach. The novel proteins identified from our study needs to be explored further for their role in the disease pathogenesis of rheumatoid arthritis and osteoarthritis.

Sartaj Ahmad and Raja Sekhar Nirujogi contributed equally to this article.
Oleanolic acid attenuates renal fibrosis in mice with unilateral ureteral obstruction via facilitating nuclear translocation of Nrf2
Authors: Chung Sungjin , Yoon Hye Eun , Kim Soo Jeong , Kim Sung Jun , Koh Eun Sil , Hong Yu Ah , Park Cheol Whee , Chang Yoon Sik , Shin Seok Joon
Published: January 2014

Background

Renal interstitial fibrosis is a common final pathological process in the progression of kidney disease. This is primarily due to oxidative stress, which contributes to renal inflammation and fibrosis. Nuclear factor-erythroid-2-related factor 2 (Nrf2) is known to coordinate induction of genes that encode antioxidant enzymes. We investigated the effects of oleanolic acid, a known Nrf2 activator, on oxidative stress-induced renal inflammation and fibrosis.

Methods

One day before unilateral ureteral obstruction (UUO) performed in C57BL/6 mice, oleanolic acid treatment was initiated and was continued until 3 and 7 days after UUO. Renal inflammation and fibrosis, markers of oxidative stress, and changes in Nrf2 expression were subsequently evaluated.

Results

In the obstructed kidneys of UUO mice, oleanolic acid significantly attenuated UUO-induced collagen deposition and fibrosis on day 7. Additionally, significantly less inflammatory cell infiltration, a lower ratio of Bax to Bcl-2 expression, and fewer apoptotic cells on TUNEL staining were observed in the obstructed kidneys of oleanolic acid-treated mice. Oleanolic acid increased the expression of nuclear Nrf2, heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1 and heat shock protein 70, and decreased lipid peroxidation in the obstructed kidney of UUO mice. There were no changes in the expression of total Nrf2 and Kelch-like ECH-associated protein 1, indicating that oleanolic acid enhanced nuclear translocation of Nrf2.

Conclusions

These results suggest that oleanolic acid may exert beneficial effects on renal fibrosis by increasing nuclear translocation of Nrf2 and subsequently reducing renal oxidative stress.
Progressive dyspnea in patient with large mediastinal mass
Authors: Fukuhara Shinichi , Dimitrova Kamellia R , Geller Charles M , Hoffman Darryl M , Ko Wilson , Tranbaugh Robert F
Published: January 2014

Liposarcoma occurs very rarely in the mediastinum. Patients often remain asymptomatic until it grows large enough to cause direct invasion or compression of adjacent organs. We report a case of a 77-year-old male presented with dyspnea of exertion and was found to have a large mediastinal mass which was eventually diagnosed as primary mediastinal well-differentiated liposarcoma. The limited respiratory function at the initial presentation prompted phrenic nerve preserving incomplete resection rather than radical removal of the adjacent mediastinal structures. After surgical removal, the recurrence for well-differentiated mediastinal liposarcomas in the mediastinum is unknown; therefore, close follow-up is crucial.