bluuebunny/crossref_metadata_2025 huggingface dataset:
Attachment and barriers to cervical screening
Authors: Hill Erin M , Gick Mary L
Published: August 2012

The present study explored the role of attachment insecurity in cervical screening behaviors and barriers in a sample of 257 female undergraduates. Information on attachment dimensions as well as attachment style was collected. Attachment anxiety and attachment avoidance were associated with decreased likelihood of having participated in cervical screening and positively associated with screening barriers. Screening barriers were elevated among individuals with insecure attachment styles (preoccupied, fearful, and dismissing), and dismissing participants were less likely to have engaged in screening compared to secure participants. Our findings demonstrate that attachment insecurity may be a risk factor for inadequate cervical screening and screening barriers.
To end life or not to prolong life: The effect of message framing on attitudes toward euthanasia
Authors: Gamliel Eyal
Published: August 2012

People ascribe “euthanasia” different values and view it differently. This study hypothesized that a different framing of objectively the same euthanasia situations would affect people’s attitudes toward it. Indeed, “positive” framing of euthanasia as not prolonging life resulted in more support for both passive and active euthanasia relative to “negative” framing of the objectively same situations as ending life. Two experiments replicated this pattern using either continuous measures of attitude or dichotomous measures of choice. The article offers two theoretical explanations for the effect of message framing on attitudes toward euthanasia, discusses implications of this effect, and suggests future research.
An update on the use of ambrisentan in pulmonary arterial hypertension
Authors: D’Alto Michele
Published: August 2012

The development of effective oral treatments that are capable of modulating the activity of endothelin receptor 1 (ET-1) represents a significant milestone in the field of pulmonary arterial hypertension (PAH). Randomized clinical trials confirm that endothelin receptor antagonist (ERA) treatments confer significant improvements on important clinical endpoints, such as exercise capacity, functional class, quality of life and pulmonary hemodynamics. Moreover, ERAs may prevent or delay clinical worsening and retard disease progression.

Ambrisentan is a propanoic acid-based ERA, showing preferential affinity for the type A ET-1 over the type B receptor. It provides another valuable, effective treatment option in PAH. Two large, randomized-placebo controlled trials demonstrated the efficacy of ambrisentan in PAH at improving exercise tolerance as measured by the 6 min walk distance. Additional secondary measures of improvement including time to clinical worsening, survival, functional class, quality of life and hemodynamic variables have been reported in clinical trials. A favorably low incidence of aminotransferase elevation indicating lower hepatic toxicity than other ERAs has been observed. Ambrisentan can be safely administered with warfarin or sildenafil without the need for dose adjustment of either therapy. A once daily oral medication with relatively few side effects is an attractive option, especially as the use of therapies in combination continues to increase. Long-term data and hemodynamic data confirm the benefits can be compared with other ERAs with fewer drug–drug interactions and a better liver safety profile.
Assessment scales in dementia
Authors: Sheehan Bart
Published: August 2012

Dementia involves progressive and often remorseless decline in cognition, function, behaviour and care needs. Assessment in dementia relies on collateral as well as patient-derived information. Many assessment scales have been developed over decades for use in dementia research and care. These scales are used to reduce uncertainty in decision making, for example in screening for cognitive impairment, making diagnoses of dementia and monitoring change. Ideal scales used in dementia should demonstrate face validity and concurrent validity against gold standard assessments, should be reliable, practical, and should rely on objective rather than subjective information. Assessment scales in the domains of cognition, function, behaviour, quality of life, depression in dementia, carer burden and overall dementia severity are reviewed in this article. The practical use of these scales in clinical practice and in research is discussed.
Experience with sorafenib in the treatment of advanced renal cell carcinoma
Authors: Procopio Giuseppe , Verzoni Elena , Testa Isabella , Nicolai Nicola , Salvioni Roberto , DeBraud Filippo
Published: August 2012

The molecular-targeted agent sorafenib is the first anticancer agent able to slow the progression of advanced/metastatic renal cell carcinoma, a tumor that was formerly refractory to conventional therapy. Experience from everyday clinical practice and investigations exploring the suitability of this agent for patients with harmful pathological conditions has extended the use of sorafenib to other settings of renal cell carcinoma and to particular risk populations. The aim of this review is to provide evidence on the most effective and safe use of sorafenib. The review pays particular attention to patients who have several comorbidities, such as impaired renal and cardiac function, and older patients whose frailty due to impaired organ function necessitates the most careful administration of targeted antineoplastic agents.
Inflammatory Markers in Pediatric Obesity
Authors: Stolzman Stacy , Bement Marie Hoeger
Published: August 2012

The prevalence of childhood obesity has recently peaked in the USA with ~17% of children considered obese. With the increase in adiposity that occurs with weight gain, a persistent low-grade inflammatory state is created. The most commonly studied inflammatory markers associated with obesity are the cytokines, tumor necrosis factor α and interleukin-6, and the acute-phase reactant, C-reactive protein. Understanding the relation between adiposity and inflammation is an important concept because these inflammatory markers influence insulin sensitivity, glucose metabolism, and atherosclerosis, ultimately leading to impaired health. In addition to obesity, physical inactivity is associated with elevated inflammatory markers. The literature, however, is inconsistent as to whether the association between physical activity and inflammation is independent of adiposity. In some obese children, physical fitness appears to circumvent the increase in inflammatory markers that are associated with obesity. The purpose of this review is to examine the relation between adiposity and inflammatory markers, including potential health implications and the impact of physical activity. We exposed a dearth of literature in understanding the interaction between obesity and physical activity on inflammatory markers, especially in children because their anthropometrics change. This review highlights the necessity for further research to better understand the complexity of the chronic inflammatory state associated with obesity.
Keeping the Spark Alive
Authors: Muise Amy , Impett Emily A. , Kogan Aleksandr , Desmarais Serge
Published: August 2012

How can couples keep the sexual spark alive in long-term relationships? The current study draws upon existing research and theory on both communal relationships and approach-avoidance models of social motivation to test the hypothesis that individual differences in the motivation to meet a partner’s sexual needs, termed sexual communal strength, predict heightened feelings of sexual desire in long-term partnerships. In a 21-day daily experience study of 44 long-term couples, individuals higher in sexual communal strength engaged in daily sexual interactions for approach goals, and in turn, reported high levels of daily sexual desire. Sexual communal strength also buffered against declines in sexual desire over a 4-month period of time. These associations held after controlling for general communal strength, relationship satisfaction, sexual frequency, age, and whether or not the couples had children. These findings demonstrate the utility of extending theories of communal motivation to the sexual domain of relationships.
The human GFI136N variant induces epigenetic changes at the Hoxa9 locus and accelerates K-RAS driven myeloproliferative disorder in mice
Authors: Khandanpour Cyrus , Krongold Joseph , Schütte Judith , Bouwman Frederique , Vassen Lothar , Gaudreau Marie-Claude , Chen Riyan , Calero-Nieto Fernando J. , Diamanti Evangelia , Hannah Rebecca , Meyer Sara E. , Grimes H. Leighton , van der Reijden Bert A. , Jansen Joop H. , Patel Chandrashekhar V. , Peeters Justine K. , Löwenberg Bob , Dührsen Ulrich , Göttgens Bertie , Möröy Tarik
Published: August 2012

The coding single nucleotide polymorphism GFI136N in the human gene growth factor independence 1 (GFI1) is present in 3%-7% of whites and increases the risk for acute myeloid leukemia (AML) by 60%. We show here that GFI136N, in contrast to GFI136S, lacks the ability to bind to the Gfi1 target gene that encodes the leukemia-associated transcription factor Hoxa9 and fails to initiate histone modifications that regulate HoxA9 expression. Consistent with this, AML patients heterozygous for the GFI136N variant show increased HOXA9 expression compared with normal controls. Using ChipSeq, we demonstrate that GFI136N specific epigenetic changes are also present in other genes involved in the development of AML. Moreover, granulomonocytic progenitors, a bone marrow subset from which AML can arise in humans and mice, show a proliferative expansion in the presence of the GFI136N variant. In addition, granulomonocytic progenitors carrying the GFI136N variant allele have altered gene expression patterns and differ in their ability to grow after transplantation. Finally, GFI136N can accelerate a K-RAS driven fatal myeloproliferative disease in mice. Our data suggest that the presence of a GFI136N variant allele induces a preleukemic state in myeloid precursors by deregulating the expression of Hoxa9 and other AML-related genes.
Interim FDG-PET in Hodgkin lymphoma: a compass for a safe navigation in clinical trials?
Authors: Gallamini Andrea , Kostakoglu Lale
Published: August 2012

Despite the rewarding results achieved in the treatment of Hodgkin lymphoma (HL), concerns have been raised regarding the long-term complications induced by therapy. Hence, the current challenge is to develop a new therapeutic strategy maintaining excellent patient outcome while reducing potentially life-threatening late adverse effects. Therefore, it would be beneficial to identify chemoresistant or refractory patients early during therapy for appropriate and timely escalation of treatment. Recently, compelling data have emerged on the prognostic role of interim [18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) performed early during the course of treatment to predict ultimate outcome, even proving superior to conventional prognostic factors. Several ongoing prospective trials are exploring the feasibility of treatment de-escalation strategies in patients with a negative interim PET, as well as therapy escalation in advanced-stage HL patients who have a positive interim PET result. In this article, the published reports on the contribution of interim PET to the design of ongoing response-adapted clinical trials are reviewed. Moreover, some of the unresolved issues revolving around the suboptimal positive predictive value of interim PET are addressed with an emphasis on the interpretation criteria. A final remark on the appropriate use of interim PET is also provided.
How I treat anticoagulated patients undergoing an elective procedure or surgery
Authors: Spyropoulos Alex C. , Douketis James D.
Published: August 2012

The periprocedural management of patients receiving long-term oral anticoagulant therapy remains a common but difficult clinical problem, with a lack of high-quality evidence to inform best practices. It is a patient's thromboembolic risk that drives the need for an aggressive periprocedural strategy, including the use of heparin bridging therapy, to minimize time off anticoagulant therapy, while the procedural bleed risk determines how and when postprocedural anticoagulant therapy should be resumed. Warfarin should be continued in patients undergoing selected minor procedures, whereas in major procedures that necessitate warfarin interruption, heparin bridging therapy should be considered in patients at high thromboembolic risk and in a minority of patients at moderate risk. Periprocedural data with the novel oral anticoagulants, such as dabigatran, rivaroxaban, and apixaban, are emerging, but their relatively short half-life, rapid onset of action, and predictable pharmacokinetics should simplify periprocedural use. This review aims to provide a practical, clinician-focused approach to periprocedural anticoagulant management.
Multi-scale agent-based brain cancer modeling and prediction of TKI treatment response: Incorporating EGFR signaling pathway and angiogenesis
Authors: Sun Xiaoqiang , Zhang Le , Tan Hua , Bao Jiguang , Strouthos Costas , Zhou Xiaobo
Published: August 2012

Background

The epidermal growth factor receptor (EGFR) signaling pathway and angiogenesis in brain cancer act as an engine for tumor initiation, expansion and response to therapy. Since the existing literature does not have any models that investigate the impact of both angiogenesis and molecular signaling pathways on treatment, we propose a novel multi-scale, agent-based computational model that includes both angiogenesis and EGFR modules to study the response of brain cancer under tyrosine kinase inhibitors (TKIs) treatment.

Results

The novel angiogenesis module integrated into the agent-based tumor model is based on a set of reaction–diffusion equations that describe the spatio-temporal evolution of the distributions of micro-environmental factors such as glucose, oxygen, TGFα, VEGF and fibronectin. These molecular species regulate tumor growth during angiogenesis. Each tumor cell is equipped with an EGFR signaling pathway linked to a cell-cycle pathway to determine its phenotype. EGFR TKIs are delivered through the blood vessels of tumor microvasculature and the response to treatment is studied.

Conclusions

Our simulations demonstrated that entire tumor growth profile is a collective behaviour of cells regulated by the EGFR signaling pathway and the cell cycle. We also found that angiogenesis has a dual effect under TKI treatment: on one hand, through neo-vasculature TKIs are delivered to decrease tumor invasion; on the other hand, the neo-vasculature can transport glucose and oxygen to tumor cells to maintain their metabolism, which results in an increase of cell survival rate in the late simulation stages.
The impact of random frequency-dependent mutations on the average population fitness
Authors: Huang Weini , Werner Benjamin , Traulsen Arne
Published: August 2012

Background

In addition to selection, the process of evolution is accompanied by stochastic effects, such as changing environmental conditions, genetic drift and mutations. Commonly it is believed that without genetic drift, advantageous mutations quickly fixate in a halpoid population due to strong selection and lead to a continuous increase of the average fitness. This conclusion is based on the assumption of constant fitness. However, for frequency dependent fitness, where the fitness of an individual depends on the interactions with other individuals in the population, this does not hold.

Results

We propose a mathematical model that allows to understand the consequences of random frequency dependent mutations on the dynamics of an infinite large population. The frequencies of different types change according to the replicator equations and the fitness of a mutant is random and frequency dependent. To capture the interactions of different types, we employ a payoff matrix of variable size and thus are able to accommodate an arbitrary number of mutations. We assume that at most one mutant type arises at a time. The payoff entries to describe the mutant type are random variables obeying a probability distribution which is related to the fitness of the parent type.

Conclusions

We show that a random mutant can decrease the average fitness under frequency dependent selection, based on analytical results for two types and simulations for n types. Interestingly, in the case of at most two types the probabilities to increase or decrease the average fitness are independent of the concrete probability density function. Instead, they only depend on the probability that the payoff entries of the mutant are larger than the payoff entries of the parent type.
Coevolution between simple sequence repeats (SSRs) and virus genome size
Authors: Zhao Xiangyan , Tian Yonglei , Yang Ronghua , Feng Haiping , Ouyang Qingjian , Tian You , Tan Zhongyang , Li Mingfu , Niu Yile , Jiang Jianhui , Shen Guoli , Yu Ruqin
Published: August 2012

Background

Relationship between the level of repetitiveness in genomic sequence and genome size has been investigated by making use of complete prokaryotic and eukaryotic genomes, but relevant studies have been rarely made in virus genomes.

Results

In this study, a total of 257 viruses were examined, which cover 90% of genera. The results showed that simple sequence repeats (SSRs) is strongly, positively and significantly correlated with genome size. Certain repeat class is distributed in a certain range of genome sequence length. Mono-, di- and tri- repeats are widely distributed in all virus genomes, tetra- SSRs as a common component consist in genomes which more than 100 kb in size; in the range of genome < 100 kb, genomes containing penta- and hexa- SSRs are not more than 50%. Principal components analysis (PCA) indicated that dinucleotide repeat affects the differences of SSRs most strongly among virus genomes. Results showed that SSRs tend to accumulate in larger virus genomes; and the longer genome sequence, the longer repeat units.

Conclusions

We conducted this research standing on the height of the whole virus. We concluded that genome size is an important factor in affecting the occurrence of SSRs; hosts are also responsible for the variances of SSRs content to a certain degree.
Normalization of a chromosomal contact map
Authors: Cournac Axel , Marie-Nelly Hervé , Marbouty Martial , Koszul Romain , Mozziconacci Julien
Published: August 2012

Background

Chromatin organization has been increasingly studied in relation with its important influence on DNA-related metabolic processes such as replication or regulation of gene expression. Since its original design ten years ago, capture of chromosome conformation (3C) has become an essential tool to investigate the overall conformation of chromosomes. It relies on the capture of long-range trans and cis interactions of chromosomal segments whose relative proportions in the final bank reflect their frequencies of interactions, hence their spatial proximity in a population of cells. The recent coupling of 3C with deep sequencing approaches now allows the generation of high resolution genome-wide chromosomal contact maps. Different protocols have been used to generate such maps in various organisms. This includes mammals, drosophila and yeast. The massive amount of raw data generated by the genomic 3C has to be carefully processed to alleviate the various biases and byproducts generated by the experiments. Our study aims at proposing a simple normalization procedure to minimize the influence of these unwanted but inevitable events on the final results.

Results

Careful analysis of the raw data generated previously for budding yeast S. cerevisiae led to the identification of three main biases affecting the final datasets, including a previously unknown bias resulting from the circularization of DNA molecules. We then developed a simple normalization procedure to process the data and allow the generation of a normalized, highly contrasted, chromosomal contact map for S. cerevisiae. The same method was then extended to the first human genome contact map. Using the normalized data, we revisited the preferential interactions originally described between subsets of discrete chromosomal features. Notably, the detection of preferential interactions between tRNA in yeast and CTCF, PolII binding sites in human can vary with the normalization procedure used.

Conclusions

We quantitatively reanalyzed the genomic 3C data obtained for S. cerevisiae, identified some of the biases inherent to the technique and proposed a simple normalization procedure to analyse them. Such an approach can be easily generalized for genomic 3C experiments in other organisms. More experiments and analysis will be necessary to reach optimal resolution and accuracies of the maps generated through these approaches. Working with cell population presenting highest levels of homogeneity will prove useful in this regards.
A population-based study on the association between acute renal failure (ARF) and the duration of polypharmacy
Authors: Chang Yi-Ping , Huang San-Kuei , Tao Ping , Chien Ching-Wen
Published: August 2012

Background

Because of the rapid growth in elderly population, polypharmacy has become a serious public health issue worldwide. Although acute renal failure (ARF) is one negative consequence of polypharmacy, the association between the duration of polypharmacy and ARF remains unclear. We therefore assessed this association using a population-based database.

Methods

Data were collected from the Taiwan National Health Insurance Research Database (NHIRD) from 2003 through 2006. The case group included patients hospitalized for ARF during 2006, but not admitted due to trauma, surgery, burn trauma, car accident, transplantation, or infectious diseases; the control group included patients hospitalized without ARF. The cumulative number of days of polypharmacy (defined as more than 5 prescriptions per day) for 1 year prior to admission was determined, with patients further subdivided into 4 categories: less than 30 days, 31–90 days, 91–180 days, and over 181 days. The dependent variable was ARF, and the control variables were age, gender, comorbidities in patients hospitalized for ARF, stay in ICUs during ARF hospitalization and site of operation for prior admissions within one month of ARF hospitalization.

Results

Of 20,790 patients who were admitted to hospitals for ARF in 2006, 12,314 (59.23 %) were male and more than 60 % were older than 65 years. Of patients with and without ARF, 16.14 % and 10.61 %, respectively, received polypharmacy for 91–180 days and 50.22 % and 24.12 %, respectively, for over 181 days. A statistical model indicated that, relative to patients who received polypharmacy for less than 30 days, those who received polypharmacy for 31–90, 91–180 and over 181 days had odds ratios of developing ARF of 1.33 (p<0.001), 1.65 (p<0.001) and 1.74 (p<0.001), respectively.

Conclusions

We observed statistically significant associations between the duration of polypharmacy and the occurrence of ARF.
Association of response to hepatitis B vaccination and survival in dialysis patients
Authors: Lin Shih-Yi , Liu Jiung-Hsiun , Wang Shu-Ming , Wang I-Kuan , Tsai Chen-An , Liu Yao-lung , Lin Hsin-Hung , Chang Chiz-Chung , Huang Chiu-Ching
Published: August 2012

Background

The status of immunocompromised patients is well recognized in end stage renal disease (ESRD). As described recently, this acquired immune dysfunction in the uremic milieu may be one of the main pathogenic factors for mortality in ESRD. The aim of this study was to determine the relationship between the immune response following a hepatitis B vaccination (HBV vaccination) and the survival of maintenance dialysis patients.

Methods

A total of 156 patients (103 on hemodialysis and 53 on continuous ambulatory peritoneal dialysis) were recruited. After receiving a full dose of the HBV vaccination, all patients were followed up for to 5 years to evaluate the association of patient survival, cause of mortality, and immune response.

Results

The response rate to the hepatitis B vaccination was 70.5%. There was no significant association between the immune response and the 5-year survival rate (p =0.600) or between the post-vaccination anti-HBs titers and the 5-year survival rate (p = 0.201). The logistic prediction model with the coefficient as non-response following HBV vaccination, diabetes mellitus, old age, and low albumin level could significantly predict infection-cause mortality (sensitivity = 0.842, specificity = 0.937).

Conclusion

There was no significant association between the immune response to HBV vaccination and the 5-year survival rate. However, non-response following HBV vaccination might be associated with infection-cause mortality in dialysis patients.
The comparative effectiveness of statin therapy in selected chronic diseases compared with the remaining population
Authors: Sheng Xia , Murphy Michael J , MacDonald Thomas M , Wei Li
Published: August 2012

Background

Total cholesterol (TC) concentration is the most commonly used measure of statin efficacy in the UK. This study aimed to evaluate the effectiveness of statins in lowering TC, cardiovascular events (CV) and mortality five common chronic diseases (chronic obstructive pulmonary disease (COPD), osteoarthritis (OA), rheumatoid arthritis (RA), chronic kidney disease (CKD), and diabetes mellitus (DM)) and to compare effectiveness with the rest of the population not recorded as having these diseases.

Methods

A population-based cohort study was conducted in Tayside population who had at least two TC measurements between 1993 and 2007. There were 12,140 patients with chronic diseases and 9,481 patients in the rest of the population not recorded as having these chronic diseases. The main outcomes were TC change from baseline, CV events and all-cause mortality.

Results

Statin-associated TC reductions varied from 15% to 28% with baseline value of between 5.1 and 5.9 mmol/L in the primary prevention (PP) and from 7% to 23% with baseline value of 4.5 to 5.2 mmol/L in the secondary prevention (SP) among chronic diseases patients. In the rest of the population, TC reductions with statins were 31% in PP and 28% in SP with baselines of 6.3 mmol/L and 5.3 mmol/L, respectively (test of heterogeneity with chronic disease groups: p < 0.001). A notional reduction of 0.5 mmol/L in TC predicted variable reductions in incident CV events of 30% in RA, 19% in CKD, and 20% in DM, and recurrent CV events by 62% in COPD, 16% in CKD, and 19% in DM. The corresponding figures for the rest of population were 12% for incident CV events and 17% for the recurrent CV events, respectively. Risk reductions for all-cause mortality varied from 20% to 36% in PP and from 18% to 40% in SP, except in OA or RA patients in the chronic diseases and 11% in PP and 16% in the rest of population (test of heterogeneity: p > 0.05).

Conclusions

The effectiveness of statins in common chronic diseases varied. With the exception of diabetes, statins tends to be less effective in patients with the chronic diseases compared with the rest of the study population. Changes in TC with statins appear not to correlate well with the changes in cardiovascular events and all-cause mortality.
Throughput and delay analysis of network coded ALOHA in wireless networks
Authors: Lee Hyun-kwan , Hwang June , Kim Seong-Lyun , Jäntti Riku
Published: August 2012

The purpose of this article is to analyze the impact of network coding in wireless networks. We consider a network coded ALOHA that performs bi-directional network coding over the ALOHA MAC protocol in a star topology network. The transmission probabilities of each outer node and the center node, and the target signal-to-interference-plus-noise ratio (SINR) are jointly optimized to achieve the maximum throughput of coded ALOHA. We analyze and compare the optimal performance of slotted and coded ALOHA. Under the unsaturated traffic condition at the center node, we derive practical throughput and delay, considering the network coding opportunity and the maximum queue length of the center node. Under the saturated traffic condition, we obtain a throughput upper bound of coded ALOHA to judge the ideal gain of network coding. The impact of asymmetric topology is evaluated with simulations.
Pavement crack characteristic detection based on sparse representation
Authors: Sun Xiaoming , Huang Jianping , Liu Wanyu , Xu Mantao
Published: August 2012

Pavement crack detection plays an important role in pavement maintaining and management. The three-dimensional (3D) pavement crack detection technique based on laser is a recent trend due to its ability of discriminating dark areas, which are not caused by pavement distress such as tire marks, oil spills and shadows. In the field of 3D pavement crack detection, the most important thing is the accurate extraction of cracks in individual pavement profile without destroying pavement profile. So after analyzing the pavement profile signal characteristics and the changeability of pavement crack characteristics, a new method based on the sparse representation is developed to decompose pavement profile signal into a summation of the mainly pavement profile and cracks. Based on the characteristics of the pavement profile signal and crack, the mixed dictionary is constructed with an over-complete exponential function and an over-complete trapezoidal membership function, and the signal is separated by learning in this mixed dictionary with a matching pursuit algorithm. Some experiments were conducted and promising results were obtained, showing that we can detect the pavement crack efficiently and achieve a good separation of crack from pavement profile without destroying pavement profile.
Protein expression profiling of inflammatory mediators in human temporal lobe epilepsy reveals co-activation of multiple chemokines and cytokines
Authors: Kan Anne A , de Jager Wilco , de Wit Marina , Heijnen Cobi , van Zuiden Mirjam , Ferrier Cyrill , van Rijen Peter , Gosselaar Peter , Hessel Ellen , van Nieuwenhuizen Onno , de Graan Pierre N E
Published: August 2012

Mesial temporal lobe epilepsy (mTLE) is a chronic and often treatment-refractory brain disorder characterized by recurrent seizures originating from the hippocampus. The pathogenic mechanisms underlying mTLE remain largely unknown. Recent clinical and experimental evidence supports a role of various inflammatory mediators in mTLE. Here, we performed protein expression profiling of 40 inflammatory mediators in surgical resection material from mTLE patients with and without hippocampal sclerosis, and autopsy controls using a multiplex bead-based immunoassay. In mTLE patients we identified 21 upregulated inflammatory mediators, including 10 cytokines and 7 chemokines. Many of these upregulated mediators have not previously been implicated in mTLE (for example, CCL22, IL-7 and IL-25). Comparing the three patient groups, two main hippocampal expression patterns could be distinguished, pattern I (for example, IL-10 and IL-25) showing increased expression in mTLE + HS patients compared to mTLE-HS and controls, and pattern II (for example, CCL4 and IL-7) showing increased expression in both mTLE groups compared to controls. Upregulation of a subset of inflammatory mediators (for example, IL-25 and IL-7) could not only be detected in the hippocampus of mTLE patients, but also in the neocortex. Principle component analysis was used to cluster the inflammatory mediators into several components. Follow-up analyses of the identified components revealed that the three patient groups could be discriminated based on their unique expression profiles. Immunocytochemistry showed that IL-25 IR (pattern I) and CCL4 IR (pattern II) were localized in astrocytes and microglia, whereas IL-25 IR was also detected in neurons. Our data shows co-activation of multiple inflammatory mediators in hippocampus and neocortex of mTLE patients, indicating activation of multiple pro- and anti-epileptogenic immune pathways in this disease.
Differential pH-dependent cellular uptake pathways among foamy viruses elucidated using dual-colored fluorescent particles
Authors: Stirnnagel Kristin , Schupp Dorothee , Dupont Aurélie , Kudryavtsev Volodymyr , Reh Juliane , Müllers Erik , Lamb Don C , Lindemann Dirk
Published: August 2012

Background

It is thought that foamy viruses (FVs) enter host cells via endocytosis because all FV glycoproteins examined display pH-dependent fusion activities. Only the prototype FV (PFV) glycoprotein has also significant fusion activity at neutral pH, suggesting that its uptake mechanism may deviate from other FVs. To gain new insights into the uptake processes of FV in individual live host cells, we developed fluorescently labeled infectious FVs.

Results

N-terminal tagging of the FV envelope leader peptide domain with a fluorescent protein resulted in efficient incorporation of the fluorescently labeled glycoprotein into secreted virions without interfering with their infectivity. Double-tagged viruses consisting of an eGFP-tagged PFV capsid (Gag-eGFP) and mCherry-tagged Env (Ch-Env) from either PFV or macaque simian FV (SFVmac) were observed during early stages of the infection pathway. PFV Env, but not SFVmac Env, containing particles induced strong syncytia formation on target cells. Both virus types showed trafficking of double-tagged virions towards the cell center. Upon fusion and subsequent capsid release into the cytosol, accumulation of naked capsid proteins was observed within four hours in the perinuclear region, presumably representing the centrosomes. Interestingly, virions harboring fusion-defective glycoproteins still promoted virus attachment and uptake, but failed to show syncytia formation and perinuclear capsid accumulation. Biochemical and initial imaging analysis indicated that productive fusion events occur predominantly within 4–6 h after virus attachment. Non-fused or non-fusogenic viruses are rapidly cleared from the cells by putative lysosomal degradation. Quantitative monitoring of the fraction of individual viruses containing both Env and capsid signals as a function of time demonstrated that PFV virions fused within the first few minutes, whereas fusion of SFVmac virions was less pronounced and observed over the entire 90 minutes measured.

Conclusions

The characterized double-labeled FVs described here provide new mechanistic insights into FV early entry steps, demonstrating that productive viral fusion occurs early after target cell attachment and uptake. The analysis highlights apparent differences in the uptake pathways of individual FV species. Furthermore, the infectious double-labeled FVs promise to provide important tools for future detailed analyses on individual FV fusion events in real time using advanced imaging techniques.
First report of canine ocular thelaziosis by Thelazia callipaeda in Portugal
Authors: Vieira Lisete , Rodrigues Filipa T , Costa Álvaro , Diz-Lopes Duarte , Machado João , Coutinho Teresa , Tuna Joana , Latrofa Maria Stefania , Cardoso Luís , Otranto Domenico
Published: August 2012

Background

Thelazia callipaeda eyeworms are transmitted by the non-biting insect vector Phortica variegata in Europe and infest the conjunctiva(s) of several mammalians, including dogs and humans. Infested hosts might remain asymptomatic or display clinical manifestations characterized by variable degrees of severity.

Methods

From July to November 2011, nine dogs were detected with eyeworms at two veterinary clinics in Chaves and Bragança (North of Portugal). Nematodes collected from dogs were morphologically and molecularly characterized at species level.

Results

Nematodes were identified as T. callipaeda. The number of worms collected from each dog ranged from three to 76 (average = 17.9 ± 26.8) and was not associated with the severity of clinical signs. Ocular discharge and conjunctivitis were observed in all dogs and ocular pruritus occurred in six of them. Polymerase chain reaction and sequencing of a portion of target cytochrome c oxidase subunit 1 gene further identified all nematodes as haplotype 1.

Conclusions

This is the first report of T. callipaeda and associated ocular disease in dogs from Portugal, suggesting that thelaziosis should be included in the differential diagnosis of canine ocular affections. The risk of the infestation spreading from Spain and France to Portugal, through domestic dogs or wild mammals, is realistic.
Anaplasma phagocytophilum in horses and ticks in Tunisia
Authors: M’ghirbi Youmna , Yaïch Hèla , Ghorbel Abderazek , Bouattour Ali
Published: August 2012

Background

Anaplasma phagocytophilum, the causative agent of granulocytic anaplasmosis, affects several species of wild and domesticated mammals, including horses. We used direct and indirect methods to compare and evaluate exposure toA. phagocytophilumin horses in northern Tunisia.

Methods

Serum from 60 horses was tested by IFA for antibodies toA. phagocytophilum, and whole blood was tested forA. phagocytophilum16S rRNA gene using a nested-PCR. To examine the risk ofA. phagocytophilumtransmission, 154 ticks that had been collected from horses were examined for the presence ofA. phagocytophilumby nested-PCR targeting 16S rRNA gene.

Results

This is the first time thatA. phagocytophilumhas been detected in horses in Tunisia, with an overall seroprevalence of 40/60 (67%). Six of the seroreactive samples (10%) had an IFA titer of 1:80, 14 (23%) of 1:160, 8 (13%) of 1:320 and 12 (20%) a titer 1 ≥ 640. The seroprevalence revealed no significant regional and sex differences. In contrast, a significant difference was observed between breeds. Eight (13%) of the horses were positive forA. phagocytophilumin the PCR, with no significant breed and age differences.Hyalomma marginatumwas a predominant tick species (130/154),and 3 were infected byA. phagocytophilum(a prevalence of 2.3%). The concordance rate ofA. phagocytophilumdetection between IFA and PCR had akvalue of −0.07.

Conclusions

The results presented in this study suggest that horses infested by ticks in Tunisia are exposed toA. phagocytophilum.
Gene expression profile suggests that pigs (Sus scrofa) are susceptible to Anaplasma phagocytophilum but control infection
Authors: Galindo Ruth C , Ayllón Nieves , Smrdel Katja Strašek , Boadella Mariana , Beltrán-Beck Beatriz , Mazariegos María , García Nerea , de la Lastra José M Pérez , Avsic-Zupanc Tatjana , Kocan Katherine M , Gortazar Christian , de la Fuente José
Published: August 2012

Background

Anaplasma phagocytophiluminfects a wide variety of hosts and causes granulocytic anaplasmosis in humans, horses and dogs and tick-borne fever in ruminants. Infection withA. phagocytophilumresults in the modification of host gene expression and immune response. The objective of this research was to characterize gene expression in pigs (Sus scrofa) naturally and experimentally infected withA. phagocytophilumtrying to identify mechanisms that help to explain low infection prevalence in this species.

Results

For gene expression analysis in naturally infected pigs, microarray hybridization was used. The expression of differentially expressed immune response genes was analyzed by real-time RT-PCR in naturally and experimentally infected pigs. Results suggested thatA. phagocytophiluminfection affected cytoskeleton rearrangement and increased both innate and adaptive immune responses by up regulation of interleukin 1 receptor accessory protein-like 1 (IL1RAPL1), T-cell receptor alpha chain (TCR-alpha), thrombospondin 4 (TSP-4) and Gap junction protein alpha 1 (GJA1) genes. Higher serum levels of IL-1 beta, IL-8 and TNF-alpha in infected pigs when compared to controls supported data obtained at the mRNA level.

Conclusions

These results suggested that pigs are susceptible toA. phagocytophilumbut control infection, particularly through activation of innate immune responses, phagocytosis and autophagy. This fact may account for the low infection prevalence detected in pigs in some regions and thus their low or no impact as a reservoir host for this pathogen. These results advanced our understanding of the molecular mechanisms at the host-pathogen interface and suggested a role for newly reported genes in the protection of pigs againstA. phagocytophilum.
Synthesis and antibacterial activity of novel levofloxacin derivatives containing a substituted thienylethyl moiety
Authors: Mohammadhosseini Negar , Alipanahi Zahra , Alipour Eskandar , Emami Saeed , Faramarzi Mohammad Ali , Samadi Nasrin , Khoshnevis Nika , Shafiee Abbass , Foroumadi Alireza
Published: August 2012

Background and the purpose of the study

Piperazinyl quinolones such as ciprofloxacin, ofloxacin and levofloxacin are an important group of quinolone antimicrobials which are widely used in the treatment of various infectious diseases. In the present study, we synthesized a new series of levofloxacin derivatives and evaluated their antibacterial activities.

Methods

The N-substituted analogs of levofloxacin 6a–j were prepared by nucleophilic reaction of N-desmethyl levofloxacin 11 with thienylethyl bromide derivatives 8 or 9. All target compounds were tested using conventional agar dilution method in comparison to levofloxacin and N-desmethyl levofloxacin and their MIC values were determined against a panel of Gram-positive and Gram-negative bacteria.

Results

All compounds showed significant antibacterial activities against Gram-positive bacteria (MIC = 0.04-6.25 μg/mL); however, the activity against Gram-negative bacteria was lower (MIC = 1.56–100 μg/mL). As is evident from the data, oxime derivatives 6e, 6h and 6i are superior in inhibiting the growth of Gram-positive bacteria (MIC = 0.04–0.19 μg/mL), and their activities were found to be 5–25 times better than N-desmethyl levofloxacin 11 and equal or better than levofloxacin 4.

Conclusion

We have designed and synthesized novel quinolone derivatives bearing functionalized thienylethyl moiety on the piperazine ring of levofloxacin. The results of antibacterial screening against Gram-positive and Gram-negative bacteria revealed that the introduction of functionalized thienylethyl moiety on the piperazine ring of levofloxacin can improve the activity against Gram-positive bacteria. Gram-positive bacteria are responsible for a wide range of infectious diseases, and rising resistance in this group is causing increasing concern. Thus, this study introduces structural features of levofloxacin scaffold for development of new candidates in the field of anti-Gram positive chemotherapy
Altered sodium channel-protein associations in critical illness myopathy
Authors: Kraner Susan D , Novak Kevin R , Wang Qingbo , Peng Junmin , Rich Mark M
Published: August 2012

Background

During the acute phase of critical illness myopathy (CIM) there is inexcitability of skeletal muscle. In a rat model of CIM, muscle inexcitability is due to inactivation of sodium channels. A major contributor to this sodium channel inactivation is a hyperpolarized shift in the voltage dependence of sodium channel inactivation. The goal of the current study was to find a biochemical correlate of the hyperpolarized shift in sodium channel inactivation.

Methods

The rat model of CIM was generated by cutting the sciatic nerve and subsequent injections of dexamethasone for 7 days. Skeletal muscle membranes were prepared from gastrocnemius muscles, and purification and biochemical analyses carried out. Immunoprecipitations were performed with a pan-sodium channel antibody, and the resulting complexes probed in Western blots with various antibodies.

Results

We carried out analyses of sodium channel glycosylation, phosphorylation, and association with other proteins. Although there was some loss of channel glycosylation in the disease, as assessed by size analysis of glycosylated and de-glycosylated protein in control and CIM samples, previous work by other investigators suggest that such loss would most likely shift channel inactivation gating in a depolarizing direction; thus such loss was viewed as compensatory rather than causative of the disease. A phosphorylation site at serine 487 was identified on the NaV 1.4 sodium channel α subunit, but there was no clear evidence of altered phosphorylation in the disease. Co-immunoprecipitation experiments carried out with a pan-sodium channel antibody confirmed that the sodium channel was associated with proteins of the dystrophin associated protein complex (DAPC). This complex differed between control and CIM samples. Syntrophin, dystrophin, and plectin associated strongly with sodium channels in both control and disease conditions, while β-dystroglycan and neuronal nitric oxide synthase (nNOS) associated strongly with the sodium channel only in CIM. Recording of action potentials revealed that denervated muscle in mice lacking nNOS was more excitable than control denervated muscle.

Conclusion

Taken together, these data suggest that the conformation/protein association of the sodium channel complex differs in control and critical illness myopathy muscle membranes; and suggest that nitric oxide signaling plays a role in development of muscle inexcitability.
Control of Allergic Rhinitis and Asthma Test (CARAT) can be used to assess individual patients over time
Authors: Fonseca Joao A , Nogueira‐Silva Luis , Morais‐Almeida Mario , Sa‐Sousa Ana , Azevedo Luis F , Ferreira Jose , Branco‐Ferreira Manuel , Rodrigues‐Alves Rodrigo , Bugalho‐Almeida Antonio , Bousquet Jean
Published: August 2012

Background

The Control of Allergic Rhinitis and Asthma Test (CARAT10) has been proposed as the first tool to implement the Allergic Rhinitis and its Impact on Asthma initiative guidelines in clinical practice. To serve this purpose, it must have adequate properties to assess the control of an individual over time. This study aimed to prospectively assess the test‐retest reliability, responsiveness and longitudinal validity of CARAT10.

Methods

Adults with asthma and allergic rhinitis were enrolled at 4 outpatient clinics of Portuguese central hospitals. At each of the two visits, 4 to 6 weeks apart, patients filled out CARAT10 and additional questionnaires, followed by a medical evaluation blinded to the questionnaires’ answers.

Results

From the 62 patients included, 51 patients completely filled out CARAT10 at both visits. The test‐retest reliability, computed as an intra‐class correlation coefficient, was 0.82. Regarding responsiveness, a significant change (p = 0.002) of CARAT10 score in clinically unstable patients was observed (95%CI ‐5.08; ‐1.31) and the Guyatt's responsiveness index was 1.54. As for the longitudinal validity assessment, the correlation coefficients of the changes of CARAT10 scores with those of ACQ5 and symptoms VAS ranged from 0.49 to 0.65, while with the physician assessment of control they ranged from 0.31 to 0.41.

Conclusion

CARAT10 has good test‐retest reliability, responsiveness and longitudinal validity. It can be used to assess control of allergic rhinitis and asthma, both to compare groups in clinical studies and to evaluate individual patients in clinical practice.
Preparation of nanostructured TiO2-based photocatalyst by controlling the calcining temperature and pH
Authors: Uddin Mohammed Jasim , Islam Md Akhtarul , Haque Sheikh Ariful , Hasan Saidul , Amin Mohammad Shaiful Alam , Rahman Mohammed Mastabur
Published: August 2012

Nanostructured TiO2 has been synthesized using one-step sol–gel method and characterized by different characterization techniques (SEM, EDS, XRD, and UV–vis spectroscopy). The photocatalytic degradation of methylene blue (MB) and Congo red (CR) is studied with the synthesized TiO2. The photocatalytic degradation data has been validated using several kinetic models. The TiO2 showed efficient photocatalytic degradation performance on MB and CR. In addition to this, the effect of pH on the photocatalytic degradation has been investigated. The TiO2 showed enhanced photocatalytic performance in basic media than that in neutral or acidic ones.