bluuebunny/crossref_metadata_2025 huggingface dataset:
Tualang Honey Promotes Apoptotic Cell Death Induced by Tamoxifen in Breast Cancer Cell Lines
Authors: Yaacob Nik Soriani , Nengsih Agustine , Norazmi Mohd. Nor
Published: February 2013

Tualanghoney (TH) is rich in flavonoids and phenolic acids and has significant anticancer activity against breast cancer cells comparable to the effect of tamoxifen (TAM),in vitro. The current study evaluated the effects of TH when used in combination with TAM on MCF-7 and MDA-MB-231 cells. We observed that TH promoted the anticancer activity of TAM in both the estrogen receptor-(ER-)responsive and ER-nonresponsive human breast cancer cell lines. Flow cytometric analyses indicated accelerated apoptosis especially in MDA-MB-231 cells and with the involvement of caspase-3/7, -8 and -9 activation as shown by fluorescence microscopy. Depolarization of the mitochondrial membrane was also increased in both cell lines when TH was used in combination with TAM compared to TAM treatment alone. TH may therefore be a potential adjuvant to be used with TAM for reducing the dose of TAM, hence, reducing TAM-induced adverse effects.
The Investigational Aurora Kinase A Inhibitor MLN8237 Induces Defects in Cell Viability and Cell-Cycle Progression in Malignant Bladder Cancer Cells In Vitro and In Vivo
Authors: Zhou Ning , Singh Kamini , Mir Maria C. , Parker Yvonne , Lindner Daniel , Dreicer Robert , Ecsedy Jeffrey A. , Zhang Zhongfa , Teh Bin T. , Almasan Alexandru , Hansel Donna E.
Published: February 2013

Purpose: Despite more than 70,000 new cases of bladder cancer in the United States annually, patients with advanced disease have a poor prognosis due to limited treatment modalities. We evaluated Aurora kinase A, identified as an upregulated candidate molecule in bladder cancer, as a potential therapeutic target.

Experimental Design: Gene expression in human bladder cancer samples was evaluated using RNA microarray and quantitative reverse transcriptase PCR. Effects of the Aurora kinase A inhibitor MLN8237 (Millennium) on cell dynamics in malignant T24 and UM-UC-3 and papilloma-derived RT4 bladder cells were evaluated in vitro and in vivo in a mouse xenograft model.

Results: A set of 13 genes involved in the mitotic spindle checkpoint, including Aurora kinases A and B, were upregulated in human urothelial carcinoma compared with normal urothelium. The Aurora kinase A inhibitor MLN8237 induced cell-cycle arrest, aneuploidy, mitotic spindle failure, and apoptosis in the human bladder cancer cell lines T24 and UM-UC-3. MLN8237 also arrested tumor growth when administered orally over 4 weeks in a mouse bladder cancer xenograft model. Finally, in vitro sequential administration of MLN8237 with either paclitaxel or gemcitabine resulted in synergistic cytotoxic effects in T24 cells.

Conclusions: Mitotic spindle checkpoint dysfunction is a common characteristic of human urothelial carcinoma and can be exploited with pharmacologic Aurora A inhibition. Given our demonstration of the ability of the Aurora A inhibitor MLN8237 to inhibit growth of bladder cancer in vitro and in vivo, we conclude that Aurora kinase inhibitors warrant further therapeutic investigation in bladder cancer. Clin Cancer Res; 19(7); 1717–28. ©2013 AACR.
De Novo Suprasellar Arachnoid Cyst: Case Report and Review of the Literature
Authors: Invergo Darbi , Tomita Tadanori
Published: February 2013

Purpose: We present a case of a 4-year-old child who was incidentally found to have a suprasellar arachnoid cyst (SAC) after initial CT imaging at 6 weeks of age but who demonstrated no anomalies. This is only the sixth case of intracranial de novo ACs documented in the English literature and only the second case of SAC to arise de novo. Methods: Case review after an SAC was found on an MRI scan at 4 years of age which had not been present on a previous CT of the head. Results: Apparent de novo SAC formation in a healthy 4-year-old female without a history of intracranial infection, surgery or trauma. Conclusion: The pathophysiology leading to the formation of the cyst might well be congenital, although there is some question as to how early in development the cysts are formed as our child was a 32-week GA preemie with an initial scan at 38 weeks GA. With the use of fast MRI scans instead of CT scans and the continued neuroimaging of premature infants, we can take a better look at the anatomy and better determine the timing of development of the SAC.
A Phase I Study of the Oral Platinum Agent Satraplatin in Combination with Oral Vinorelbine in Patients with Advanced Solid Malignancies
Authors: Gallerani Elisa , Cathomas Richard , Sessa Cristiana , Digena Tiziana , Bartosek Anna Amalia , Zotto Laura Dal , von Moos Roger
Published: February 2013

Background: The broad spectrum of antitumor activity of the oral platinum satraplatin (S) and vinorelbine (V) were the rationale for performing a phase I trial to define the maximum tolerated (MTD) and the recommended (RD) dose in adult patients with advanced solid tumors. Patients and Methods: 4 dose levels (DLs) of S (mg/m2/day, days 1–5) and V (mg/m2/day, days 1, 8, 15, and 22) every 28 days were explored: S60/V60 on days 1, 8 and 15 only; S60/V60; S70/V60; and S80/V60. Subsequently, 3 further DLs were evaluated with V omitted on day 22: S70/V60, S80/V60, and S80/V80. Results: Treating 27 patients, the MTD was S80/V80 on days 1, 8, and 15, with 2 dose-limiting toxicities in 2 patients (nausea and vomiting grade (G) 3 with skipping of V on day 15, and neutropenia G4 with infection). The RD was S80/V60 on days 1, 8, and 15. The most frequent toxicities (any G) were nausea (70%), diarrhea (59%), anorexia (37%), vomiting (33%), asthenia (26%), constipation (26%), and paresthesia (18%). Partial responses were observed in 2 platinum-sensitive ovarian cancer patients and in 1 prostate cancer patient. Conclusion: The combination of S and V is tolerable at a DL of S80/V60 on days 1, 8, and 15; further evaluations in platinum- and V-sensitive tumor types would be of interest.
Markers CD40, VEGF, AKT, PI3K, and S100 Correlate with Tumor Stage in Gastric Cancer
Authors: Tian Wen-Yan , Chen Wei-Chang , Li Rui , Liu Lei
Published: February 2013

Background: To better understand gastric cancer occurrence and prognosis, we explored the expression of molecules in the CD40 pathway and their correlation with gastric cancer prognosis. Patients and Methods: We measured the expression of CD40, VEGF, AKT, PI3K, and S100 in gastric cancer tissues and adjacent normal tissues from 128 patients by immunohistochemistry. Results: The expression of CD40, VEGF, AKT, and PI3K were significantly higher in tumor tissue than in normal tissue, while S100 expression in dendritic cells (DC) was lower. Expression of CD40, VEGF, AKT, and PI3K significantly increased with T stage, while S100 expression decreased with T stage. Lymph node metastasis was associated with low or negative S100 expression. PI3K expression increased with clinical stage, while negative S100 expression was associated with higher clinical stages. Multivariate analysis did not indicate significant associations between any of these markers and recurrence or mortality. Conclusion: The correlation between T stage of gastric cancer and the higher expression of CD40, VEGF, AKT, and PI3K, along with lower S100 expression in DC, may provide insights into future targets for more effective immunotherapy for cancer.
Mucopolysaccharidosis Type II and the G374sp Mutation
Authors: Martínez-Quintana E. , Rodríguez-González F.
Published: February 2013

Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is a rare, X-linked disease caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase, which catalyses a step in the catabolism of glycosaminoglycans resulting in accumulation of heparan and dermatan sulfate in many organs and tissues. This accumulation favors the appearance of neurologic involvement, severe airway obstruction, skeletal deformities, and cardiomyopathy, especially mitral and aortic valve regurgitation. In severe cases, obstructive airway disease and cardiac failure due to valvular dysfunction are the most common causes of death within the second decade of life. However, in mild cases, intelligence remains normal, stature is almost normal and death usually occurs due to cardiac failure in the fourth decade of life. We report the presentation, diagnosis, management, and outcome of 2 siblings with MPS II and the G374sp mutation at the nucleotide c.1246 of the gene encoding for the iduronate-2-sulfatase.
Near-infrared Spectroscopy–mediated Neurofeedback Enhances Efficacy of Motor Imagery–based Training in Poststroke Victims
Authors: Mihara Masahito , Hattori Noriaki , Hatakenaka Megumi , Yagura Hajime , Kawano Teiji , Hino Taro , Miyai Ichiro
Published: February 2013

Background and Purpose—

Despite the findings that motor imagery and execution are supposed to share common neural networks, previous studies using imagery-based rehabilitation have revealed inconsistent results. In the present study, we investigated whether feedback of cortical activities (neurofeedback) using near-infrared spectroscopy could enhance the efficacy of imagery-based rehabilitation in stroke patients.

Methods—

Twenty hemiplegic patients with subcortical stroke received 6 sessions of mental practice with motor imagery of the distal upper limb in addition to standard rehabilitation. Subjects were randomly allocated to REAL and SHAM groups. In the REAL group, cortical hemoglobin signals detected by near-infrared spectroscopy were fed back during imagery. In the SHAM group, irrelevant randomized signals were fed back. Upper limb function was assessed using the finger and arm subscales of the Fugl-Meyer assessment and the Action Research Arm Test.

Results—

The hand/finger subscale of the Fugl-Meyer assessment showed greater functional gain in the REAL group, with a significant interaction between time and group (
F
2,36
=15.5;
P
<0.001). A significant effect of neurofeedback was revealed even in severely impaired subjects. Imagery-related cortical activation in the premotor area was significantly greater in the REAL group than in the SHAM group (
T
58
=2.4;
P
<0.05).

Conclusions—

Our results suggest that near-infrared spectroscopy–mediated neurofeedback may enhance the efficacy of mental practice with motor imagery and augment motor recovery in poststroke patients with severe hemiparesis.
Hydrological Cycles over the Congo and Upper Blue Nile Basins: Evaluation of General Circulation Model Simulations and Reanalysis Products
Authors: Siam Mohamed S. , Demory Marie-Estelle , Eltahir Elfatih A. B.
Published: February 2013

The simulations and predictions of the hydrological cycle by general circulation models (GCMs) are characterized by a significant degree of uncertainty. This uncertainty is reflected in the range of Intergovernmental Panel on Climate Change (IPCC) GCM predictions of future changes in the hydrological cycle, particularly over major African basins. The confidence in GCM predictions can be increased by evaluating different GCMs, identifying those models that succeed in simulating the hydrological cycle under current climate conditions, and using them for climate change studies. Reanalyses are often used to validate GCMs, but they also suffer from an inaccurate representation of the hydrological cycle. In this study, the aim is to identify GCMs and reanalyses' products that provide a realistic representation of the hydrological cycle over the Congo and upper Blue Nile (UBN) basins. Atmospheric and soil water balance constraints are employed to evaluate the models' ability to reproduce the observed streamflow, which is the most accurate measurement of the hydrological cycle. Among the ECMWF Interim Re-Analysis (ERA-Interim), NCEP–NCAR reanalysis, and 40-yr ECWMF Re-Analysis (ERA-40), ERA-Interim shows the best performance over these basins: it balances the water budgets and accurately represents the seasonal cycle of the hydrological variables. The authors find that most GCMs used by the IPCC overestimate the hydrological cycle compared to observations. They observe some improvement in the simulated hydrological cycle with increased horizontal resolution, which suggests that some of the high-resolution GCMs are better suited for climate change studies over Africa.
Improving the Human–Computer Dialogue With Increased Temporal Predictability
Authors: Weber Florian , Haering Carola , Thomaschke Roland
Published: February 2013

Objective:

An experiment was conducted to investigate the impacts of length and variability of system response time (SRT) on user behavior and user experience (UX) in sequential computing tasks.

Background:

Length is widely considered to be the most important aspect of SRTs in human–computer interaction. Research on temporal attention shows that humans adjust to temporal structures and that performance substantially improves with temporal predictability.

Method:

Participants performed a sequential task with simulated office software. Duration and variability, that is, the number of different SRTs, was manipulated. Lower variability came at the expense of on average higher durations. User response times, task execution times, and failure rates were measured to assess user performance. UX was measured with a questionnaire.

Results:

A reduction in variability improved user performance significantly. Whereas task load and failure rates remained constant, responses were significantly faster. Although a reduction in variability came along with, on average, increased SRTs, no difference in UX was found.

Conclusion:

Considering SRT variability when designing software can yield considerable performance benefits for the users. Although reduced variability comes at the expense of overall longer SRTs, the interface is not subjectively evaluated to be less satisfactory or demanding. Time design should aim not only at reducing average SRT length but also at finding the optimum balance of length and variability.

Application:

Our findings can easily be applied in any user interface for sequential tasks. User performance can be improved without loss of satisfaction by selectively prolonging particular SRTs to reduce variability.
Combined effects of sensory cueing and limb activation on unilateral neglect in subacute left hemiplegic stroke patients: a randomized controlled pilot study
Authors: Fong Kenneth NK , Yang Nicole YH , Chan Marko KL , Chan Dora YL , Lau Andy FC , Chan Dick YW , Cheung Joyce TY , Cheung Hobby KY , Chung Raymond CK , Chan Chetwyn CH
Published: February 2013

Objective:

To compare the effects of contralesional sensory cueing and limb activation with that of sham control in the treatment of unilateral neglect after stroke.

Design:

A randomized, single-blinded, sham-controlled pilot study.

Setting:

Two rehabilitation hospitals.

Subjects:

Forty subacute left hemiplegic stroke inpatients with unilateral neglect.

Interventions:

Participants were assigned randomly to 1 of 2 groups. The experimental group wore a wristwatch cueing device over the hemiplegic arm for three hours a day, five days per week, for three weeks, and also underwent conventional rehabilitation. Patients were encouraged to move their hemiplegic arm five consecutive times after each prompt. The sham group underwent the same rehabilitation process, except they wore a sham device.

Main measures:

Neglect, arm motor performance, and overall functioning were assessed pre- and posttraining, and at follow-up.

Results:

There were no significant differences between groups in outcome measures except the neglect drawing tasks ( p = 0.034) (the mean gain score from baseline to follow-up assessment was 5.2 (3.7) in the experimental group and 1.9 (3.5) in the sham group), across three time intervals. The experimental group showed greater improvement in arm motor performance than did the sham group.

Conclusion:

The results did not confirm that sensory cueing and limb activation treatment is effective when compared with those receiving placebo to reduce unilateral neglect, but it might be useful for promoting hemiplegic arm performance in stroke patients.
Dyspnea Coping Strategies in Korean Immigrants With Asthma or Chronic Obstructive Pulmonary Disease
Authors: Park Soo Kyung , Stotts Nancy A. , Douglas Marilyn K. , Donesky-Cuenco DorAnne , Carrieri-Kohlman Virginia
Published: February 2013

Purpose: Patients with lung disease develop coping strategies to relieve dyspnea. The coping strategies of Korean immigrants, however, are poorly understood. The purpose of this study was to describe the strategies that Korean immigrants with asthma or chronic obstructive pulmonary disease (COPD) use to cope with dyspnea and to compare similarities and differences in coping strategies between the two conditions. Design: Outpatients with asthma ( n = 25) or COPD ( n = 48) participated in a cross-sectional descriptive study. Method: Open-ended questions and a structured instrument were used to describe coping strategies for dyspnea. Descriptive and inferential statistics were used to analyze the data. Results: The most prevalent strategy was “I keep still or rest.” Korean immigrants also used traditional therapies to manage dyspnea. Conclusions: Although the coping strategies of Korean immigrants were similar to those of other ethnic groups, they incorporated elements of Asian medical practice and herbs. This finding enables health care providers to better understand Korean immigrants’ efforts to overcome dyspnea and to guide their patients’ approach to coping.
Hierarchical control by a higher center and the rhythm generator contributes to realize adaptive locomotion
Authors: Hioki Tomoko , Miyazaki Yuko , Nishii Jun
Published: February 2013

Many cyclic movements of vertebrates are produced by a rhythm generator in the spinal cord, which is often referred to as the central pattern generator. Meanwhile, higher centers, such as the cerebellum, are also involved in motor control. In this study, we discuss the control and learning mechanisms of these two control systems, focusing on the following problems: (1) how these two control systems generate a motor command cooperatively without conflict, and (2) how these control systems acquire motor commands. As a possible model to solve these problems, we propose a hierarchical motor control learning model on the basis of physiological knowledge. This model assumes that the higher center learns the timing and amplitude of a motor command and sends control signals to the rhythm generator. The rhythm generator is tuned by the control signals and acquires the ability to output a motor command to realize a target motion. By applying this model to a simulation experiment of the learning control of a one-dimensional hopping robot, hopping at a desired height was successful. Our simulation results also show that a multiple control system involving the higher center and rhythm generator is more robust than a single control system.
General and Maladaptive Traits in a Five-Factor Framework for DSM-5 in a University Student Sample
Authors: De Fruyt Filip , De Clercq Barbara , De Bolle Marleen , Wille Bart , Markon Kristian , Krueger Robert F.
Published: February 2013

The relationships between two measures proposed to describe personality pathology, that is the Revised NEO Personality Inventory (NEO-PI-3) and the Personality Inventory for DSM-5 (PID-5), are examined in an undergraduate sample ( N = 240). The NEO inventories are general trait measures, also considered relevant to assess disordered personality, whereas the PID-5 measure is specifically designed to assess pathological personality traits, as conceptualized in the DSM-5 proposal. A structural analysis of the 25 PID-5 traits confirmed the factor structure observed in the U.S. derivation sample, with higher order factors of Negative Affectivity, Detachment, Antagonism, Disinhibition, and Psychoticism. A joint factor analysis of, respectively, the NEO domains and their facets with the PID-5 traits showed that general and maladaptive traits are subsumed under an umbrella of five to six major dimensions that can be interpreted from the perspective of the five-factor model or the Personality Psychopathology Five. Implications for the assessment of personality pathology and the construction of models of psychopathology grounded in personality are discussed.
Strategies and Help-Seeking Behavior Among Mexican Women Experiencing Partner Violence
Authors: Frías Sonia M.
Published: February 2013

According to a recent Mexican survey, 10.72% of women have at some point experienced sexual partner violence, and 23.71% physical violence at the hands of their current or last partner. Using this survey and a series of semi-structured interviews with experts, this study used a mixed-methods approach to examine, first, whether women who experienced violence turned to law enforcement agencies for help, and the characteristics of these women. Second, the research examined what type of service and treatment they reported receiving from these agencies. Finally, the research examined reasons women did not request help from police and law enforcement agencies.
“En el Grupo Tomas Conciencia (In Group You Become Aware)”
Authors: Parra-Cardona José Rubén , Escobar-Chew Ana Rocío , Holtrop Kendal , Carpenter Georgia , Guzmán Ricardo , Hernández Dolores , Zamudio Efraín , González Ramírez Dolores
Published: February 2013

Qualitative interviews were conducted with 21 Latino immigrant men who participated in a culturally informed batterer intervention. The objectives of this investigation were twofold. First, to identify the treatment components that facilitated the participants’ willingness to engage in a process of change aimed at terminating their abusive behaviors. Second, to describe the treatment components that led to their satisfaction with the intervention. Research findings confirm that the Spanish version of the Duluth curriculum can be beneficial for Latino immigrant batterers. Results also demonstrate the critical role of culture as it refers to content of the intervention and method of delivery.
Asset or liability? An analysis of the effect of changes in party membership on partisan ideological change
Authors: Rohlfing Ingo
Published: February 2013

The role of members of political parties is ambiguous because it entails both benefits and costs. In order to shed light on the question of whether members are an asset or a liability for parties, I examine whether parties use their ideology on a left–right dimension as a collective incentive for the appeal to actual and potential party members. A quantitative analysis of the effects of changes in membership on partisan ideological change, covering 61 parties in 11 Western democracies from the 1950s to the early 1990s, shows that there is a weak, but statistically significant, effect. An additional analysis of two mechanisms by which membership has an effect refutes the alternative explanation that positional changes of the median member account for partisan ideological change. In total, the results indicate that members are both an asset and a liability and that parties try to keep the two in balance.
The good, the bad and the voter
Authors: van Spanje Joost , de Vreese Claes
Published: February 2013

Hate speech prosecution of politicians is a common phenomenon in established democracies. Examples of politicians tried for hate speech include Nick Griffin in Britain and Jean-Marie Le Pen in France. Does hate speech prosecution of politicians affect the electoral support for their party? This is an important question, as the parties involved typically are controversial, often accused of stirring up political cynicism or political violence. The relevant literature has largely ignored this question, however. In this article, we use data from a representative sample of Dutch voters interviewed before and re-interviewed after the unexpected court decision to prosecute MP Geert Wilders. We demonstrate empirically that the decision substantially enhanced his party’s appeal. This resulted in an immediate increase in support for the party by one to five percentage points among those who are moderately in favour of the assimilation of ethnic minorities into Dutch culture. In addition, the evidence suggests that the decision contributed to the party’s subsequent electoral lift-off. Our findings call for investigations into the electoral effects of legal proceedings against political actors in democratic systems worldwide.
The use of literacy bags promotes parental involvement in Chinese children’s literacy learning in the English language
Authors: Huang SuHua
Published: February 2013

This study employed an ethnographic methodology to explore the use of ‘literacy bags’ (LBs) to promote parental involvement in Chinese children’s literacy learning in the English language. It was conducted with a first-grade class consisting of 18 students and their parents in Taiwan. Data resources were obtained from teaching questionnaires, classroom observation, home visits, and parental interviews. Each LB contained an English language children’s picture book and CD or audiotape, along with some extension activities. Students took an LB home every Friday and parents spent time reading and doing the activities with their children. The results of this study highlighted the way in which LBs encouraged, supported, and enriched book reading and literacy learning in families. This study also demonstrated that parents expanded their understanding of how a child develops a new language, and they were able to apply effective literacy strategies to engage and discuss books with their children. Reading activities promoted social interactions between parents and children, parents and teachers, and peer interactions. The project also influenced parental attitudes and perceptions of their children’s English literacy development, viewing themselves as teachers of their own children. In addition, this study expanded the scope of the findings of Western scholars to include understandings of the cultures, languages, and families of East Asia.
The Culture Industry, New Media, and the Shift from Creation to Curation; or, Enlightenment As a Kick in the Nuts
Authors: Wiggins Benjamin Alan
Published: February 2013

This article analyzes Pranked—a reality-TV show that takes amateur videos from YouTube and formats them into MTV broadcasts—to reconsider the culture industry as social media reconfigures it. For television’s first seven decades, the calculated infliction of severe pain on unsuspecting victims was not deemed suitable for mass consumption. To explain why such broadcasts are possible now, this study analyzes the underappreciated role of entertainment insurers, advancements in social media technologies that allowed the culture industry to circumvent entertainment insurers, and a subcultural turn that valorized sadistic pranking. By offloading risk from the insured and compensated professionals of traditional media to the uninsured and uncompensated amateurs of social media, Pranked inaugurates a fundamentally novel shift in the culture industry: a shift from creation to curation. The article concludes by returning to Horkheimer and Adorno’s original culture industry critique to assess the stakes of the turn from broadcasting distraction to broadcasting suffering.
Cellular distribution of lipid A and LPS R595 after in vitro application to isolated human monocytes by freeze-fracture replica immunogold-labelling
Authors: Richter Walter , Heinbockel Lena , Kaconis Yani , Steiniger Frank , Gutsmann Thomas , Brade Lore , Brandenburg Klaus
Published: February 2013

We have performed freeze-fracture replica immunogold labelling of endotoxin preparations (lipid A and deep rough mutant LPS Re from Salmonella enterica sv. Minnesota), i.e. adding the endotoxins to human monocytes, labelling with monoclonal Abs recognizing either lipid A or LPS Re (A6 and A20 respectively), and fixing with immunogold secondary Ab. We have found that the endotoxins intercalated into the cell membranes with subsequent internalization by the cells. Surprisingly, membrane uptake took place only in the inner, plasmic leaflet of the plasma membrane, but there was no uptake of the outer leaflet for both compounds. Remarkable labelling could be also found for the two membranes of the nuclear envelope—in the case of lipid A only at the plasmic leaflet, but in the case of LPS Re on both leaflets. Isothermal calorimetric titration of the AB A20 with LPS and phospholipids showed that the Ab may bind not only to LPS but also to negatively charged phosphatidylserine. These results are discussed in the frame of the published concepts of cell activation induced by the endotoxins, i.e. how they are able to cause a conformational change of signalling proteins, such as the TLR4/MD2 complex.
Chronic cerebrospinal venous insufficiency in multiple sclerosis: a highly prevalent age-dependent phenomenon
Authors: Lanzillo Roberta , Mancini Marcello , Liuzzi Raffaele , Di Donato Orlando , Salvatore Elena , Maglio Valentina , Vacca Giovanni , Amato Luca , D’Anna Gennaro , Brunetti Arturo , Brescia Morra Vincenzo
Published: February 2013

Background

This study aimed to investigate the prevalence and clinical relevance of chronic cerebrospinal venous insufficiency (CCSVI) in multiple sclerosis (MS) patients and healthy controls using extra- and intracranial colour Doppler sonography.

Methods

We examined 146 MS patients, presenting with a clinically isolated syndrome, relapsing-remitting, secondary progressive, or primary progressive MS, and 38 healthy controls. Sonographic examination was performed according to Zamboni’s protocol and was performed by three independent sonographers. The results of sonographic examination were compared with clinical and demographic characteristics of the patients.

Results

CCSVI, defined as the presence of at least two positive Zamboni’s criteria, was found in 76% of MS patients and 16% of control subjects. B-mode anomalies of internal jugular veins, such as stenosis, malformed valves, annuli, and septa were the most common lesions detected in MS patients (80.8%) and controls (47.4%). We observed a positive correlation between sonographic diagnosis of CCSVI and the patients’ age (p = 0.003). However, such a correlation was not found in controls (p = 0.635). Notably, no significant correlations were found between sonographic signs of CCSVI and clinical characteristics of MS, except for absent flow in the jugular veins, which was found more often in primary (p<0.005) and secondary (p<0.05) progressive patients compared with non-progressive patients. Absent flow in jugular veins was significantly correlated with patients’ age (p < 0.0001).

Conclusions

Sonographically defined CCSVI is common in MS patients. However, CCSVI appears to be primarily associated with the patient’s age, and poorly correlated with the clinical course of the disease.
Spatio-temporal malaria transmission patterns in Navrongo demographic surveillance site, northern Ghana
Authors: Kasasa Simon , Asoala Victor , Gosoniu Laura , Anto Francis , Adjuik Martin , Tindana Cletus , Smith Thomas , Owusu-Agyei Seth , Vounatsou Penelope
Published: February 2013

Background

The relationship between entomological measures of malaria transmission intensity and mortality remains uncertain. This is partly because transmission is heterogeneous even within small geographical areas. Studying this relationship requires high resolution, spatially structured, longitudinal entomological data. Geostatistical models that have been used to analyse the spatio-temporal heterogeneity have not considered the uncertainty in both sporozoite rate (SR) and mosquito density data. This study analysed data from Kassena-Nankana districts in northern Ghana to obtain small area estimates of malaria transmission rates allowing for this uncertainty.

Methods

Independent Bayesian geostatistical models for sporozoite rate and mosquito density were fitted to produce explicit entomological inoculation rate (EIR) estimates for small areas and short time periods, controlling for environmental factors.

Results

Mosquitoes were trapped from 2,803 unique locations for three years using mainly CDC light traps. Anopheles gambiae constituted 52%, the rest were Anopheles funestus. Mean biting rates for An. funestus and An. gambiae were 32 and 33 respectively. Most bites occurred in September, the wettest month. The sporozoite rates were higher in the dry periods of the last two years compared with the wet period. The annual EIR varied from 1,132 to 157 infective bites. Monthly EIR varied between zero and 388 infective bites. Spatial correlation for SR was lower than that of mosquito densities.

Conclusion

This study confirms the presence of spatio-temporal heterogeneity in malaria transmission within a small geographical area. Spatial variance was stronger than temporal especially in the SR. The estimated EIR will be used in mortality analysis for the area.
The impact of serological features in Chinese children with primary or past Epstein–Barr virus infections
Authors: Huang Yuan , Wei Cong , Zheng Kun , Zhao Dongchi
Published: February 2013

Background

Epstein–Barr virus (EBV) is a primary cause of infectious mononucleosis (IM) throughout the world, and the positive serology rate changes over time in infected individuals. The aim of this study was to explore the serological and clinical features among Chinese children with EBV infections. A retrospective study of children suspected of having IM was conducted. Peripheral blood samples were analyzed by indirect immunofluorescence to detect any EBV-specific antibodies. Samples were classed as positive (+) or negative (−) to immunoglobulins M (IgM) or G (IgG) to the viral capsid antigen (VCA) or EBV nuclear antigen (EBNA). A standard medical history was taken, including epidemiological data and noting any clinical manifestations.

Results

Of 317 children, 37 were aged <8 months; 10 of these were VCA-IgM+, and the youngest was aged 1 month; 280 were aged >8 months. The EBV infection rate ranged from 21.4% among subjects aged 8–12 months to 84.2% in those aged >9 years. Serologically, children who tested as VCA-IgM+ together with VCA-IgG and EBNA-IgG– had longer hospital stays with more palatal petechiae and lymphadenopathy, especially among those with an atypical lymphocyte count of >10%. Children with the serological patterns [VCA-IgM–, VCA-IgG+ and EBNA-IgG–] and [VCA-IgM+ VCA-IgG+ and EBNA-IgG+] did not show specific clinical features.

Conclusions

Infants aged <8 months could be infected with EBV. About 84% of these Chinese children aged >9 years had serological evidence of EBV infection, whereas IM peaked in patients aged 2–3 years.
Chicken faecal microbiota and disturbances induced by single or repeated therapy with tetracycline and streptomycin
Authors: Videnska Petra , Faldynova Marcela , Juricova Helena , Babak Vladimir , Sisak Frantisek , Havlickova Hana , Rychlik Ivan
Published: February 2013

Background

In this study, we characterised the microbiota present in the faeces of 15- and 46-week-old egg laying hens before and after tetracycline or streptomycin therapy. In the first experiment, the layers were subjected to 7 days of therapy. In the second experiment, the hens were subjected to two days of therapy, which was repeated for an additional two days after 12 days of antibiotic withdrawal. This enabled us to characterise dynamics of the changes after antibiotic administration and withdrawal, and to identify genera repeatedly resistant to tetracycline and streptomycin.

Results

Real-time PCRs specific for Enterobacteriales, Lactobacillales, Clostridiales and Bifidobacteriales showed that changes in the microbiota in response to antibiotic therapy and antibiotic withdrawal were quite rapid and could be observed within 24 hours after the change in therapy status. Pyrosequencing of PCR amplified V3/V4 variable regions of 16S rRNA genes showed that representatives of the orders Clostridiales, Lactobacillales, Bacteroidales, Bifidobacteriales, Enterobacteriales, Erysipelotrichales, Coriobacteriales, Desulfovibrionales, Burkholderiales, Campylobacterales and Actinomycetales were detected in the faeces of hens prior to the antibiotic therapy. Tetracycline and streptomycin therapies decreased the prevalence of Bifidobacteriales, Bacteroidales, Clostridiales, Desulfovibrionales, Burkholderiales and Campylobacterales in faecal samples in both experiments. On the other hand, Enterobacteriales and Lactobacillales always increased in prevalence in response to both therapies. Within the latter two orders, Escherichia and Enterococcus were the genera prevalence of which increased after all the antibiotic treatments.

Conclusions

The changes in microbiota composition induced by the antibiotic therapy were rapid and quite dramatic and only representatives of the genera Enterococcus and Escherichia increased in response to the therapy with both antibiotics in both experiments.
Core concepts of human rights and inclusion of vulnerable groups in the mental health policies of Malawi, Namibia, and Sudan
Authors: Mannan Hasheem , ElTayeb Shahla , MacLachlan Malcolm , Amin Mutamad , McVeigh Joanne , Munthali Alister , Van Rooy Gert
Published: February 2013

Background

One of the most crucial steps towards delivering judicious and comprehensive mental health care is the formulation of a policy and plan that will navigate mental health systems. For policy-makers, the challenges of a high-quality mental health system are considerable: the provision of mental health services to all who need them, in an equitable way, in a mode that promotes human rights and health outcomes.

Method

EquiFrame, a novel policy analysis framework, was used to evaluate the mental health policies of Malawi, Namibia, and Sudan. The health policies were assessed in terms of their coverage of 21 predefined Core Concepts of human rights (Core Concept Coverage), their stated quality of commitment to said Core Concepts (Core Concept Quality), and their inclusion of 12 Vulnerable Groups (Vulnerable Group Coverage). In relation to these summary indices, each policy was also assigned an Overall Summary Ranking, in terms of it being of High, Moderate, or Low quality.

Results

Substantial variability was identified across EquiFrame’s summary indices for the mental health policies of Malawi, Namibia, and Sudan. However, all three mental health policies scored high on Core Concept Coverage. Particularly noteworthy was the Sudanese policy, which scored 86% on Core Concept Coverage, and 92% on Vulnerable Group Coverage. Particular deficits were evident in the Malawian mental health policy, which scored 33% on Vulnerable Group Coverage and 47% on Core Concept Quality, and was assigned an Overall Summary Ranking of Low accordingly. The Overall Summary Ranking for the Namibian Mental Health Policy was High; for the Sudanese Mental Health Policy was Moderate; and for the Malawian Mental Health Policy was Low.

Conclusions

If human rights and equity underpin policy formation, it is more likely that they will be inculcated in health service delivery. EquiFrame may provide a novel and valuable tool for mental health policy analysis in relation to core concepts of human rights and inclusion of vulnerable groups, a key practical step in the successful realization of the Millennium Development Goals.
Regulatory effect of calcineurin inhibitor, tacrolimus, on IL-6/sIL-6R-mediated RANKL expression through JAK2-STAT3-SOCS3 signaling pathway in fibroblast-like synoviocytes
Authors: Choe Jung-Yoon , Park Ki-Yeun , Park Sung-Hoon , Lee Sang-Il , Kim Seong-Kyu
Published: February 2013

Introduction

This study investigated whether the calcineurin inhibitor, tacrolimus, suppresses receptor activator of NF-κB ligand (RANKL) expression in fibroblast-like synoviocytes (FLS) through regulation of IL-6/Janus activated kinase (JAK2)/signal transducer and activator of transcription-3 (STAT3) and suppressor of cytokine signaling (SOCS3) signaling.

Methods

The expression of RANKL, JAK2, STAT3, and SOCS3 proteins was assessed by western blot analysis, real-time PCR and ELISA in IL-6 combined with soluble IL-6 receptor (sIL-6R)-stimulated rheumatoid arthritis (RA)-FLS with or without tacrolimus treatment. The effects of tacrolimus on synovial inflammation and bone erosion were assessed using mice with arthritis induced by K/BxN serum. Immunofluorescent staining was performed to identify the effect of tacrolimus on RANKL and SOCS3. The tartrate-resistant acid phosphatase staining assay was performed to assess the effect of tacrolimus on osteoclast differentiation.

Results

We found that RANKL expression in RA FLS is regulated by the IL-6/sIL-6R/JAK2/STAT3/SOCS3 pathway. Inhibitory effects of tacrolimus on RANKL expression in a serum-induced arthritis mice model were identified. Tacrolimus inhibits RANKL expression in IL-6/sIL-6R-stimulated FLS by suppressing STAT3. Among negative regulators of the JAK/STAT pathway, such as CIS1, SOCS1, and SOCS3, only SOCS3 is significantly induced by tacrolimus. As compared to dexamethasone and methotrexate, tacrolimus more potently suppresses RANKL expression in FLS. By up-regulating SOCS3, tacrolimus down-regulates activation of the JAK-STAT pathway by IL-6/sIL-6R trans-signaling, thus decreasing RANKL expression in FLS.

Conclusions

These data suggest that tacrolimus might affect the RANKL expression in IL-6 stimulated FLS through STAT3 suppression, together with up-regulation of SOCS3.
MicroRNA-125b regulates the expression of aggrecanase-1 (ADAMTS-4) in human osteoarthritic chondrocytes
Authors: Matsukawa Tetsuya , Sakai Tadahiro , Yonezawa Tomo , Hiraiwa Hideki , Hamada Takashi , Nakashima Motoshige , Ono Yohei , Ishizuka Shinya , Nakahara Hiroyuki , Lotz Martin K , Asahara Hiroshi , Ishiguro Naoki
Published: February 2013

Introduction

Increased expression of aggrecanase-1 (ADAMTS-4) has emerged as an important factor in osteoarthritis (OA) and other joint diseases. This study aimed to determine whether the expression of ADAMTS-4 in human chondrocytes is regulated by miRNA.

Methods

MiRNA targets were identified using bioinformatics. Chondrocytes were isolated from knee cartilage and treated with interleukin-1 beta (IL-1β). Gene expression was quantified using TaqMan assays and protein production was determined by immunoblotting. Luciferase reporter assay was used to verify interaction between miRNA and target messenger RNA (mRNA).

Results

In silico analysis predicted putative target sequence of miR-125b on ADAMTS-4. MiR-125b was expressed in both normal and OA chondrocytes, with significantly lower expression in OA chondrocytes than in normal chondrocytes. Furthermore, IL-1β-induced upregulation of ADAMTS-4 was suppressed by overexpression of miR-125b in human OA chondrocytes. In the luciferase reporter assay, mutation of the putative miR-125b binding site in the ADAMTS-4 3'UTR abrogated the suppressive effect of miR125.

Conclusions

Our results indicate that miR-125b plays an important role in regulating the expression of ADAMTS-4 in human chondrocytes and this identifies miR-125b as a novel therapeutic target in OA.
Anti-matrix metalloproteinase-9 DNAzyme decreases tumor growth in the MMTV-PyMT mouse model of breast cancer
Authors: Hallett Miranda A , Teng Bin , Hasegawa Hisashi , Schwab Luciana P , Seagroves Tiffany N , Pourmotabbed Tayebeh
Published: February 2013

Introduction

Despite continued improvements in diagnosis, surgical techniques, and chemotherapy, breast cancer patients are still overcome by cancer metastasis. Tumor cell proliferation, invasion and metastasis are mediated, at least in part, through degradation of basement membrane by neutral matrix metalloproteinases (MMP) produced by tumor and stromal cells. Evidence suggests that MMP-9 plays a significant role in breast tumor cell invasion and metastasis. DNAzymes or catalytic oligonucleotides are new classes of gene targeting molecules that bind and cleave a specific mRNA, resulting in decreased protein expression.

Methods

The application of anti-MMP-9 DNAzyme (AM9D) for the treatment of primary and metastatic breast cancer was evaluated in vitro and in vivo using MDA-MB-231 cells and the MMTV-PyMT transgenic breast cancer mouse model. Spontaneously developed mammary tumors in MMTV-PyMT transgenic mice were treated intratumorally with naked AM9D, once a week for 4 weeks. The stability of DNAzyme was determined in vitro and in vivo using fluorescently labeled DNAzyme.

Results

AM9D specifically inhibited expression of MMP-9 in MDA-MB-231 cells resulting in reduced invasive property of these cells by 43%. Weekly intratumoral treatment of spontaneously developed mammary tumors in MMTV-PyMT transgenic mice was sufficient to significantly reduce the rate of tumor growth and final tumor load in a dose dependent and statistically significant manner (P < 0.05). This decrease in tumor growth was correlated with decreased MMP-9 protein production within the treated tumor tissues. Tumors treated with AM9D were also less vascularized and contained more apoptotic cells compared to control and untreated tumors.

Conclusions

These results show that targeting and down regulation of MMP-9 by AM9D could prove useful as a therapy against breast carcinoma tumor growth and invasion.
Phenotypic flexibility in migrating bats: seasonal variation in body composition, organ sizes and fatty acid profiles
Authors: McGuire Liam P. , Fenton M. Brock , Guglielmo Christopher G.
Published: February 2013

Many species of bats migrate long distances, but the physiological challenges of migration are poorly understood. We tested the hypothesis that migration is physiologically demanding for bats by examining migration-related phenotypic flexibility. Both bats and birds are endothermic, flying vertebrates; therefore, we predicted that migration would result in similar physiological trade-offs. We compared hoary bats (Lasiurus cinereus) during spring migration and summer non-migratory periods, comparing our results with previous observations of birds. Migrating bats had reduced digestive organs, enlarged exercise organs, and fat stores had higher proportions of polyunsaturated fatty acids (PUFAs). These results are consistent with previous studies of migrating birds; however, we also found sex differences not typically associated with bird migration. Migrating female hoary bats increased the relative size of fat stores by reducing lean body components, while males maintained the same relative amount of fat in both seasons. The ratio of n-6 to n-3 PUFA in flight muscle membrane increased in migrating males and decreased in migrating females, consistent with males using torpor more frequently than females during spring migration. Enlarged exercise organs, reduced digestive organs and changes in adipose tissue composition reflect the elevated energetic demands of migration. Sex-specific patterns of fat storage and muscle membrane composition likely reflect challenges faced by females that migrate while pregnant. Our results provide some of the first insights into the physiological demands of bat migration and highlight key differences between bats and birds.
Role of the primer activation signal in tRNA annealing onto the HIV-1 genome studied by single-molecule FRET microscopy
Authors: Beerens Nancy , Jepsen Mette D.E. , Nechyporuk-Zloy Volodymyr , Krüger Asger C. , Darlix Jean-Luc , Kjems Jørgen , Birkedal Victoria
Published: February 2013

HIV-1 reverse transcription is primed by a cellular tRNAlys3 molecule that binds to the primer binding site (PBS) in the genomic RNA. An additional interaction between the tRNA molecule and the primer activation signal (PAS) is thought to regulate the initiation of reverse transcription. The mechanism of tRNA annealing onto the HIV-1 genome was examined using ensemble and single-molecule Förster Resonance Energy Transfer (FRET) assays, in which fluorescent donor and acceptor molecules were covalently attached to an RNA template mimicking the PBS region. The role of the viral nucleocapsid (NC) protein in tRNA annealing was studied. Both heat annealing and NC-mediated annealing of tRNAlys3 were found to change the FRET efficiency, and thus the conformation of the HIV-1 RNA template. The results are consistent with a model for tRNA annealing that involves an interaction between the tRNAlys3 molecule and the PAS sequence in the HIV-1 genome. The NC protein may stimulate the interaction of the tRNA molecule with the PAS, thereby regulating the initiation of reverse transcription.