bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute disseminated encephalomyelitis followed by recurrent or monophasic optic neuritis in pediatric patients
Authors: Huppke Peter , Rostasy Kevin , Karenfort Michael , Huppke Brenda , Seidl Rainer , Leiz Steffen , Reindl Markus , Gärtner Jutta
Published: November 2012

Background:

Some pediatric patients with inflammatory demyelinating central nervous system disorders cannot be classified under any of the established disease entities, making their treatment and prognosis difficult.

Objective:

The objective of this study is to characterize a subgroup of pediatric patients with recurrent demyelinating central nervous system disorders.

Methods:

This study includes a case series of pediatric patients with monophasic or recurrent acute disseminated encephalomyelitis (ADEM) who later presented with either monophasic or recurrent optic neuritis (ON).

Results:

We describe seven patients with a median follow-up of six years (five females, two males) who presented at a median age of 6 years (range 4–8 years) with monophasic ( n = 4) or recurrent ADEM (two to four attacks) followed by monophasic ( n = 3) or recurrent ON (two to nine attacks). Cranial magnetic resonance imaging (MRI) was typical for ADEM ( n = 6) with complete or almost complete resolution of lesions on follow-up. Cerebrospinal (CSF) studies at the time of ADEM showed a pleocytosis in six patients and were negative for oligoclonal bands (OCBs) in all. In all patients high titers for serum anti-MOG antibodies were detected.

Conclusion:

ADEM followed by ON is a rare but distinct clinical phenotype among pediatric patients. Further studies are needed to allow recommendations on treatment or prognosis.
Out of left field? Explaining the variable electoral success of European radical left parties
Authors: March Luke , Rommerskirchen Charlotte
Published: November 2012

European radical left parties (RLPs) are gradually receiving greater attention. Yet, to date, what has received insufficient focus is why such parties have maintained residues of electoral support after the collapse of the USSR and why this support varies so widely. This article is the first to subject RLPs to large-n quantitative analysis, focusing on 39 parties in 34 European countries from 1990 to 2008. It uses the ‘supply and demand’ conceptual framework developed for radical right parties to identify a number of socio-economic, political-cultural and party-system variables in the external environment that might potentially affect RLP support. The article finds the most persuasive variables to include political culture (past party success), the level of unemployment, Euroscepticism and anti-globalization sentiment, the electoral threshold and competition from Green and radical right parties. The findings suggest several avenues for future research and provide a framework that can be adapted to explain the electoral success of other party families.
Type D (distressed) personality and its assessment with the DS14 in Lithuanian patients with coronary artery disease
Authors: Bunevicius Adomas , Staniute Margarita , Brozaitiene Julija , Stropute Dalia , Bunevicius Robertas , Denollet Johan
Published: November 2012

We examined Type D personality (combination of negative affectivity with social inhibition) and its assessment with the DS14 in 543 Lithuanian coronary patients. Psychometric analyses confirmed the two-factor structure, internal consistency ( α = 0.84/ α = 0.75), and test–retest reliability ( r = 0.69/0.81) of the DS14 negative affectivity and inhibition components. Negative affectivity correlated ( r = −0.58) with emotional stability and social inhibition ( r = −0.46) with extraversion; correlations with other Big-Five traits ranged between r = −0.11 and −0.19. Type D patients (34%) had a ninefold increased odds of depression (95% confidence interval = 5.01–17.36) and a fivefold increased odds of anxiety (95% confidence interval = 3.47–7.97). These findings support the validity of the Type D construct in Lithuania.
Gay and bisexual men’s human papillomavirus vaccine intentions: A theory-based structural equation analysis
Authors: Wheldon Christopher W , Buhi Eric R , Daley Ellen M
Published: November 2012

In this study, we examined the structural relationships among constructs from the Health Belief Model as they relate to human papillomavirus vaccine intentions in young gay and bisexual men in the United States ( N = 183). A model was identified that fit the data well and accounted for 56% of the variance in vaccine intentions. Perceived benefits and barriers were the most proximate predictors of intentions, whereas knowledge and perceived threat exerted only indirect influence. Clarifying the propositional structures within the Health Belief Model can help to advance our understanding of human papillomavirus–related cognitions and behaviors and inform vaccine promotion programs.
The social sharing of emotions in HIV/AIDS: A comparative study of HIV/AIDS, diabetic and cancer patients
Authors: Cantisano Nicole , Rimé Bernard , Muñoz-Sastre María T
Published: November 2012

Studies have shown that chronic illness patients encounter difficulties in the social sharing of emotions. Do HIV/AIDS patients present distinguishing traits in the inhibition of illness and non-illness-related emotions? The differences in the social sharing of emotion between 35 HIV/AIDS, 35 diabetic and 34 cancer outpatients were studied. A questionnaire assessed illness-related emotions, social sharing of emotion and emotional inhibition. The HIV/AIDS group significantly presented superior scoring in shame, guilt and non-sharing of illness-related emotions, lower frequencies of social sharing of emotion and less sharing partners. These findings could lead to future research examining the emotional expression of guilt and shame in HIV/AIDS.
Inferior Vena Cava Filter Penetration Resulting in Renal Pelvis Rupture With Urinoma Formation
Authors: Kassis Christine , Kalva Sanjeeva P.
Published: November 2012

Inferior vena cava (IVC) filter penetration is common and most often asymptomatic. However, penetration may potentially result in a variety of complications, including aortic trauma and small bowel perforation. Described is a case of IVC filter penetration resulting in renal pelvis perforation with urinoma formation.
Optimizing Treatment Switch for Virologic Failure during First-Line Antiretroviral Therapy in Resource-Limited Settings
Authors: Adetunji Adedotun A. , Achenbach Chad , Feinglass Joseph , Darin Kristin M. , Scarsi Kimberly K. , Ekong Ernest , Taiwo Babafemi O. , Adewole Isaac F. , Murphy Robert
Published: November 2012

We evaluated adult Nigerian patients with antiretroviral switch to second-line treatment with ritonavir-boosted protease inhibitor (PI/r)-based regimens due to virologic failure (confirmed HIV-1 RNA viral load [VL] >1000 copies/mL) during first-line antiretroviral therapy. Proportion of patients with VL >400 copies/mL and characteristics associated with nonsuppression during second-line treatment are described. Approximately 15% of patients (34 of 225) had VL >400 copies/mL at 1-year after treatment switch to PI/r-based regimens. In adjusted analyses, VL ≥5 log10 copies/mL at treatment switch (odds ratio [OR] 2.90 [confidence interval (CI) 1.21-6.93]); duration of first-line treatment after virologic failure >180 days (OR 2.56 [CI 1.0-6.54]); and PI/r regimen adherence <90% (OR 3.27 [CI 1.39-7.68]) were associated with VL >400 copies/mL at 1 year of second-line treatment. We therefore recommend that the maximum permissible time between suspicion of virologic failure and completion of antiretroviral treatment switch should not exceed 6 months when patients develop first-line antiretroviral failure in resource-limited settings.
Chronic pain management strategies used by low-income overweight Latinos
Authors: Rutledge Dana N , Cantero Patricia J , Ruiz Jeanette E
Published: November 2012

Objective:

The objective of this study is to examine the strategies used to manage chronic pain from the perspective of the individual in group interviews.

Methods:

Sixteen low-income overweight Latino adults participated in two group interviews facilitated by a trained moderator who inquired about the type of chronic pain suffered by participants, followed by more specific questions about pain management. Interviews were audio-recorded, transcribed verbatim (Spanish), back-translated into English, and analyzed using thematic analysis.

Results:

Participants’ pain varied in type, location, and intensity. Participants discussed pain-related changes in activities and social life, and difficulties with health care providers, and as a result, we discovered five major themes: pain-related life alterations, enduring the pain, trying different strategies, emotional suffering, and encounters with health care system/providers.

Discussion:

Findings indicated that there are opportunities for providers to improve care for low-income overweight Latinos with chronic pain by listening respectfully to how pain alters their daily lives and assisting them in feasible self-management strategies.
Living with chronic pancreatitis: a qualitative study
Authors: Cronin Patricia , Begley Cecily
Published: November 2012

Objective:

Recent literature acknowledges the impact of this progressive and debilitating disease on psychological and social well-being, but the plight of those with chronic pancreatitis remains unknown and hidden. The aim of this study was to develop an understanding of what it means to live with chronic pancreatitis.

Design:

Qualitative study based on philosophical hermeneutics using multiple unstructured interviews.

Participants:

Fourteen people with chronic pancreatitis and five relatives took part in 41 interviews in 2007–2008.

Setting:

Tertiary clinic in Ireland.

Results:

The meaning of living with chronic pancreatitis for participants in this study is ‘enduring disruption’. Enduring has a two-fold meaning; it symbolises the perpetual or permanent nature of disruption that occurs at physiological, social and psychological levels (i.e., ‘suffering’). Enduring also means ‘to tolerate’ and encompasses how the participants and their families cope and manage the overall transition from well person to a person with chronic pancreatitis.

Discussion:

This study offers an alternative perspective to previous quality of life research and presents a challenge to the emphasis on management of the pathophysiological processes and treatment of chronic pancreatitis that is decontextualised from the person’s everyday living. Healthcare professionals need to understand and support people with chronic pancreatitis.
Police controlled antecedents which significantly elevate prosecution and conviction rates in domestic violence cases
Authors: Nelson Eric L
Published: November 2012

Logistic regression was used to assess five different police actions that an investigating police officer can choose to employ when handling a domestic violence call. Each significantly increases the likelihood the prosecutor will file charges: obtain photographs (60 percent); find and arrest the defendant (94 percent); obtain an emergency protective order (87 percent); locate additional witnesses (68 percent); and list more than one criminal charge in the police report (284 percent). Three optional police actions increase the likelihood of criminal conviction: find and arrest the defendant (78 percent); obtain an emergency protective order (102 percent); list more than one charge (142 percent). Survival analysis shows a sixth action, completing the investigation the same day, to significantly increase rates of criminal case filing and also rates of criminal conviction. A strong case, best practices model for the investigation of domestic violence incidents was validated and is presented. Police discretion is discussed. Lawmakers should consider making these optional investigative actions mandatory.
At the edge: Balnakiel, a video and sound installation by artist Shona Illingworth
Authors: Albano Caterina
Published: November 2012

This article examines the analogy between film and memory through a consideration of Shona Illingworth’s video and sound installation Balnakiel (2009). In particular, the article focuses on up-to-date psychological views of memory as a spatial as well as temporal construct and on the role of the point of view in memory retrieval. Central to the argument is the link between emotion and point of view as contingent on memory as a space that we inhabit. Sigmund Freud’s concept of screen memory is revisited in the light of current memory models, drawing attention to the salience of memory perspective for emotionally problematic memories. Within this context, the cultural analogy of memory and film is indicative of the broader relevance of the moving image as a referent for the understanding of memory processes and the ways in which we affectively position ourselves in relation to emotionally disturbing memories. In Balnakiel, a work informed by these new perspectives, place and memory feature as contested sites of individual and collective recollection.
Tadalafil as monotherapy and in combination regimens for the treatment of pulmonary arterial hypertension
Authors: Udeoji Dioma U. , Schwarz Ernst R.
Published: November 2012

The purpose of this review is to evaluate the use of tadalafil as monotherapy and in combination regimens for the treatment of pulmonary arterial hypertension (PAH). A systematic English language search of the medical literature using PubMed was conducted between January 1960 and May 2012 using the search terms ‘tadalafil’, ‘therapy’, ‘pulmonary (arterial) hypertension’ and ‘combination therapy’. Special emphasis was given to controlled clinical trials and case studies relevant for the use of tadalafil in PAH. The search revealed 113 relevant publications, 31 of which were clinical trials, 52 were reviews and 12 were case reports. Of these, 12 were clinical studies in human patients with PAH who were treated with tadalafil alone, and seven were clinical studies in human patients with PAH who were treated with tadalafil in combination with other agents. Only clinical studies in human patients were included. Exclusion criteria were monotherapy other than using tadalafil and any combination therapy that excluded tadalafil as part of the treatment regimen. Overall, 1353 human subjects were studied; 896 were treated with tadalafil alone while 457 subjects were treated with tadalafil in coadministration. Tadalafil appears to be an effective and a safe treatment option for patients with PAH. It improves clinical status, exercise capacity, hemodynamic parameters, compliance issues and quality of life and reduces the occurrence of clinical worsening. Tadalafil in combination therapy seems to be additive and synergistic in relaxing pulmonary vascular muscle cells but more clinical trials on human subjects are warranted.
Patients Whose Physicians Recommend Colonoscopy and Those Who Follow Through
Authors: Daly Jeanette M. , Xu Yinghui , Levy Barcey T.
Published: November 2012

Background: More than half of eligible individuals are not up-to-date with colon cancer screening. Purpose: To assess the characteristics of those who received a colonoscopy screening recommendation and those who followed the physician recommendation. Methods: Patient self-administered questionnaire and medical record review in 16 private family physician practices. Results: From 8372 patients invited to participate, 685 were enrolled and had a medical record review; 219 (32%) had a colonoscopy recommendation and 86 (39%) received a colonoscopy. Independent factors associated with having a recommendation for colonoscopy were significantly younger in age (odds ratios [OR] = 1.6), higher incomes (annual income ≥$40 000 vs <$40 000; OR = 1.8), physician or nurse discussion about colon cancer tests (OR = 1.6), physical visit in the preceding 26 months (OR = 1.7), distant relative with colon cancer (OR = 2.4), and a medical diagnosis of hyperlipidemia (OR = 2.1). Independent factors associated with following through on colonoscopy after a recommendation were age ≥65 years (OR = 0.3), male patient (OR = 0.4), and feeling that colon cancer screening is very important (OR = 3.2). Conclusions: Socioeconomic factors are associated with receipt of a colonoscopy recommendation. Fewer than one third of patients had documentation of a physician colonoscopy recommendation and of those, less than half followed through.
Zincalstibite-9R: the first nine-layer polytype with the layered double hydroxide structure-type
Authors: Mills S. J. , Christy A. G. , Kampf A. R. , Housley R. M. , Favreau G. , Boulliard J.-C. , Bourgoin V.
Published: November 2012

Zincalstibite-9R, a new polytype in the hydrotalcite supergroup is reported from the Monte Avanza mine, Italy. It occurs as pale blue curved disc-like tablets flattened on {001} intergrown to form rosettes typically less than 50 μm in diameter, with cyanophyllite and linarite in cavities in baryte. Zincalstibite-9R is uniaxial (–), with refractive indices ω = 1.647(2) and ε = 1.626(2) measured in white light. The empirical formula (based on 12 OH groups) is (Zn1.092+Cu0.872+Al0.04)Σ2.00Al1.01(Sb0.975+Si0.02)Σ0.99(OH)12, and the ideal formula is (Zn,Cu)2Al(OH)6[Sb(OH)6]. Zincalstibite-9R crystallizes in space group R, with a = 5.340(2), c = 88.01(2) Å, V = 2173.70(15) Å3 and Z = 9. The crystal structure was refined to R1 = 0.0931 for 370 unique reflections [Fo > 4σ(F)] and R1 = 0.0944 for all 381 unique reflections. It has the longest periodic layer stacking sequence for a layered double hydroxide compound reported to date.
Palenzonaite, berzeliite, and manganberzeliite: (As5+, V5+, Si4+)O4 tetrahedra in garnet structures
Authors: Nagashima M. , Armbruster T.
Published: November 2012

Schäferite, NaCa2Mg2(V5+O4)3; palenzonaite, NaCa2Mn22+(V5+O4)3; berzeliite, NaCa2Mg2(As5+O4)3; and manganberzeliite, NaCa2Mn2+2(As5+O4)3, are cubic minerals with garnet structures (space group Iad) in which tetrahedrally coordinated V5+ and/or As5+ at the Z site are charge balanced by disordered Na+ and Ca2+ at the X site, and divalent Mg2+ and Mn2+ cations at the octahedrally coordinated Y site. The crystal chemistry of palenzonaite (from the Molinello and Gambatesa mines, Italy, and the Fianel mine, Switzerland), berzeliite (from Långban, Sweden, and Montaldo, Italy), and manganberzeliite (from Varenche, Italy, and the Gozaisho mine, Japan) were studied by electron microprobe analysis and single-crystal X-ray diffraction methods. Structure refinements converged to R1 values of 1.36–2.42%. The tetrahedral site in these garnet structures is mainly occupied by pentavalent As5+ or V5+ (only up to about 20% randomly distributed Si4+ is present). Charge balance is maintained by variations in the Ca/Na ratio at the X site. Heterovalent substitution (Na+ ↔ Ca2+) at the distorted square antiprism X site in vanadate- and arsenate-bearing garnets allows full occupancy of the octahedral Y site by divalent cations (primarily Mg2+ and Mn2+). There is a positive correlation between the  and  bond lengths and the mean ionic radii of the substituent elements, but there is no correlation between the  bond length and the variable Na/Ca site occupancy. The ionic radii of octahedrally coordinated Mg2+ and Mn2+ are such that the shared octahedral–dodecahedral edges are similar in length to the unshared octahedral edges, which is a measure of lattice distortion in garnet structures.
Spleen endothelial cells from patients with myelofibrosis harbor the JAK2V617F mutation
Authors: Rosti Vittorio , Villani Laura , Riboni Roberta , Poletto Valentina , Bonetti Elisa , Tozzi Lorenzo , Bergamaschi Gaetano , Catarsi Paolo , Dallera Elena , Novara Francesca , Massa Margherita , Campanelli Rita , Fois Gabriela , Peruzzi Benedetta , Lucioni Marco , Guglielmelli Paola , Pancrazzi Alessandro , Fiandrino Giacomo , Zuffardi Orsetta , Magrini Umberto , Paulli Marco , Vannucchi Alessandro M. , Barosi Giovanni
Published: November 2012

Increased microvessel density contributes to abnormal BM and spleen microenvironment in myelofibrosis (MF). Taking advantage of the JAK2V617F mutation as a marker of malignancy, in the present study, we investigated whether splenic endothelial cells (ECs) obtained from capillaries by laser microdissection or from fresh spleen tissue by cell culture or cell sorting harbored such mutation in patients bearing the mutation in their granulocytes and undergoing splenectomy for therapeutical reasons. To extend the analysis to the ECs of large vessels, endothelial tissue from the splenic vein was also studied. We found JAK2V617F+ ECs in 12 of 18 patients also bearing the mutation in their granulocytes. In 3 patients, the mutation was found in at least 2 different EC samples obtained by laser microdissection, cell culture, or cell sorting. The mutation was detected in the splenic vein ECs of 1 of 6 patients investigated. In conclusion, we provide evidence that some ECs from the spleen and splenic veins of patients with MF bear the JAK2V617F mutation. We suggest that splenic ECs are involved in the process of malignant transformation in MF.
Harmonic function for which the second dilatation is α-spiral
Authors: Aydog̃an Melike , Duman Emel Yavuz , Polatog̃lu Yaşar , Kahramaner Yasemin
Published: November 2012

Let

f
=
h
+

g
¯

be a harmonic function in the unit disc

D

. We will give some properties of f under the condition the second dilatation is α-spiral.

MSC:30C45, 30C55.
mGOASVM: Multi-label protein subcellular localization based on gene ontology and support vector machines
Authors: Wan Shibiao , Mak Man-Wai , Kung Sun-Yuan
Published: November 2012

Background

Although many computational methods have been developed to predict protein subcellular localization, most of the methods are limited to the prediction of single-location proteins. Multi-location proteins are either not considered or assumed not existing. However, proteins with multiple locations are particularly interesting because they may have special biological functions, which are essential to both basic research and drug discovery.

Results

This paper proposes an efficient multi-label predictor, namely mGOASVM, for predicting the subcellular localization of multi-location proteins. Given a protein, the accession numbers of its homologs are obtained via BLAST search. Then, the original accession number and the homologous accession numbers of the protein are used as keys to search against the Gene Ontology (GO) annotation database to obtain a set of GO terms. Given a set of training proteins, a set of T relevant GO terms is obtained by finding all of the GO terms in the GO annotation database that are relevant to the training proteins. These relevant GO terms then form the basis of a T-dimensional Euclidean space on which the GO vectors lie. A support vector machine (SVM) classifier with a new decision scheme is proposed to classify the multi-label GO vectors. The mGOASVM predictor has the following advantages: (1) it uses the frequency of occurrences of GO terms for feature representation; (2) it selects the relevant GO subspace which can substantially speed up the prediction without compromising performance; and (3) it adopts an efficient multi-label SVM classifier which significantly outperforms other predictors. Briefly, on two recently published virus and plant datasets, mGOASVM achieves an actual accuracy of 88.9% and 87.4%, respectively, which are significantly higher than those achieved by the state-of-the-art predictors such as iLoc-Virus (74.8%) and iLoc-Plant (68.1%).

Conclusions

mGOASVM can efficiently predict the subcellular locations of multi-label proteins. The mGOASVM predictor is available online athttp://bioinfo.eie.polyu.edu.hk/mGoaSvmServer/mGOASVM.html.
Yeast importin-β is required for nuclear import of the Mig2 repressor
Authors: Fernández-Cid Alejandra , Vega Montserrat , Herrero Pilar , Moreno Fernando
Published: November 2012

Background

Mig2 has been described as a transcriptional factor that in the absence of Mig1 protein is required for glucose repression of the SUC2 gene. Recently it has been reported that Mig2 has two different subcellular localizations. In high-glucose conditions it is a nuclear modulator of several Mig1-regulated genes, but in low-glucose most of the Mig2 protein accumulates in mitochondria. Thus, the Mig2 protein enters and leaves the nucleus in a glucose regulated manner. However, the mechanism by which Mig2 enters into the nucleus was unknown until now.

Results

Here, we report that the Mig2 protein is an import substrate of the carrier Kap95 (importin-β). The Mig2 nuclear import mechanism bypasses the requirement for Kap60 (importin-α) as an adaptor protein, since Mig2 directly binds to Kap95 in the presence of Gsp1(GDP). We also show that the Mig2 nuclear import and the binding of Mig2 with Kap95 are not glucose-dependent processes and require a basic NLS motif, located between lysine-32 and arginine-37. Mig2 interaction with Kap95 was assessed in vitro using purified proteins, demonstrating that importin-β, together with the GTP-binding protein Gsp1, is able to mediate efficient Mig2-Kap95 interaction in the absence of the importin-α (Kap60). It was also demonstrated, that the directionality of Mig2 transport is regulated by association with the small GTPase Gsp1 in the GDP- or GTP-bound forms, which promote cargo recognition and release, respectively.

Conclusions

The Mig2 protein accumulates in the nucleus through a Kap95 and NLS-dependent nuclear import pathway, which is independent of importin-α in Saccharomyces cerevisiae.
A first insight into the genotypic diversity of Mycobacterium tuberculosis from Rwanda
Authors: Gafirita James , Umubyeyi Alaine N , Asiimwe Benon B
Published: November 2012

Background

Mycobacterium tuberculosis complex (MTC) is the causative agent of tuberculosis (TB). Globally, increasing evidence shows that in M. tuberculosis, transmission varies from strain to strain and that different strains exhibit a range of geographical and host specificities, pathogenicity, and drug susceptibility. Therefore rapid and accurate differentiation of the members of MTC is critical in guiding treatment and public health decisions. We carried out a study at different health units and the National Reference Laboratory in Rwanda identify Mycobacterium tuberculosis complex species prevalent in TB patients in Rwanda. We further characterized the isolates using spoligotyping in order to gain an insight into the strain diversity of drug resistant and susceptible isolates of M. tuberculosis in this setting.

Methods

A total of 151 isolates from culture positive sputum samples were harvested, heat killed at 80°C for two hours, and then shipped to Makerere University College of Health Sciences, Uganda, for speciation and typing. Species identification was achieved by regions of difference (RD) analysis, while Spoligotyping was done to identify strain types.

Results

Region of difference analysis identified all the 151 isolates as M. tuberculosis. Spoligotyping revealed predominance of the T2 family (58.3%, 88/151), with SIT 52 being the most prevalent strain (31.8%, 48/151). Among the 151 isolates, 64 (42.4%) were multidrug resistant (MDR) with 3 cases on mono-resistance. Of 94 retreatment cases, 48 (51.1%) were MDR and of 46 newly presenting cases 14 (30.4%) were MDR. There was a significant difference (p=0.01) in anti-TB drug resistance between new and retreatment cases in the sample. However, there was no significant relationship between HIV serostatus and the two major strain types SIT 52 (p =0.15and SIT 152 (p = 0.41).

Conclusion

Mycobacterium tuberculosis is the most prevalent species of Mycobacterium tuberculosis complex in Rwanda, and SIT 52 (T2) the predominant strain. There is significantly more MDR in the retreatment cases but no significant difference was observed by HIV status in relation to any spoligotypes.
A flow cytometry-based workflow for detection and quantification of anti-plasmodial antibodies in vaccinated and naturally exposed individuals
Authors: Ajua Anthony , Engleitner Thomas , Esen Meral , Theisen Michael , Issifou Saadou , Mordmüller Benjamin
Published: November 2012

Background

Antibodies play a central role in naturally acquired immunity against Plasmodium falciparum. Current assays to detect anti-plasmodial antibodies against native antigens within their cellular context are prone to bias and cannot be automated, although they provide important information about natural exposure and vaccine immunogenicity. A novel, cytometry-based workflow for quantitative detection of anti-plasmodial antibodies in human serum is presented.

Methods

Fixed red blood cells (RBCs), infected with late stages of P. falciparum were utilized to detect malaria-specific antibodies by flow cytometry with subsequent automated data analysis. Available methods for data-driven analysis of cytometry data were assessed and a new overlap subtraction algorithm (OSA) based on open source software was developed. The complete workflow was evaluated using sera from two GMZ2 malaria vaccine trials in semi-immune adults and pre-school children residing in a malaria endemic area.

Results

Fixation, permeabilization, and staining of infected RBCs were adapted for best operation in flow cytometry. As asexual blood-stage vaccine candidates are designed to induce antibody patterns similar to those in semi-immune adults, serial dilutions of sera from heavily exposed individuals were compared to naïve controls to determine optimal antibody dilutions. To eliminate investigator effects introduced by manual gating, a non-biased algorithm (OSA) for data-driven gating was developed. OSA-derived results correlated well with those obtained by manual gating (r between 0.79 and 0.99) and outperformed other model-driven gating methods. Bland-Altman plots confirmed the agreement of manual gating and OSA-derived results. A 1.33-fold increase (p=0.003) in the number of positive cells after vaccination in a subgroup of pre-school children vaccinated with 100 μg GMZ2 was present and in vaccinated adults from the same region we measured a baseline-corrected 1.23-fold, vaccine-induced increase in mean fluorescence intensity of positive cells (p=0.03).

Conclusions

The current workflow advances detection and quantification of anti-plasmodial antibodies through improvement of a bias-prone, low-throughput to an unbiased, semi-automated, scalable method. In conclusion, this work presents a novel method for immunofluorescence assays in malaria research.
Gold nanoparticle thin films fabricated by electrophoretic deposition method for highly sensitive SERS application
Authors: Zhu Sheng-Qing , Zhang Tong , Guo Xin-Li , Wang Qi-Long , Liu Xuefeng , Zhang Xiao-Yang
Published: November 2012

We report an electrophoretic deposition method for the fabrication of gold nanoparticle (GNP) thin films as sensitive surface-enhanced Raman scattering (SERS) substrates. In this method, GNP sol, synthesized by a seed-mediated growth approach, and indium tin oxide (ITO) glass substrates were utilized as an electrophoretic solution and electrodes, respectively. From the scanning electron microscopy analysis, we found that the density of GNPs deposited on ITO glass substrates increases with prolonged electrophoresis time. The films possess high mechanical adhesion strength and exhibit strong localized surface plasmon resonance (LSPR) effect by showing high SERS sensitivity to detect 1 × 10−7 M rhodamine 6 G in methanol solution. Finally, the relationship between Raman signal amplification capability and GNP deposition density has been further investigated. The results of our experiment indicate that the high-density GNP film shows relatively higher signal amplification capability due to the strong LSPR effect in narrow gap regions between the neighboring particles on the film.
Boundary value problem of a nonlinear Langevin equation with two different fractional orders and impulses
Authors: Wang Guotao , Zhang Lihong , Song Guangxing
Published: November 2012

In this paper, we study a new type of a Langevin equation involving two different fractional orders and impulses. Sufficient conditions are formulated for the existence and uniqueness of solutions of the given problems.

MSC:34A08, 34B10, 34B37, 46N10.
CD8+ and CD4+ cytotoxic T cell escape mutations precede breakthrough SIVmac239 viremia in an elite controller
Authors: Burwitz Benjamin J , Giraldo-Vela Juan Pablo , Reed Jason , Newman Laura P , Bean Alexander T , Nimityongskul Francesca A , Castrovinci Philip A , Maness Nicholas J , Leon Enrique J , Rudersdorf Richard , Sacha Jonah B
Published: November 2012

Background

Virus-specific T cells are critical components in the containment of immunodeficiency virus infections. While the protective role of CD8+ T cells is well established by studies of CD8+ T cell-mediated viral escape, it remains unknown if CD4+ T cells can also impose sufficient selective pressure on replicating virus to drive the emergence of high-frequency escape variants. Identifying a high frequency CD4+ T cell driven escape mutation would provide compelling evidence of direct immunological pressure mediated by these cells.

Results

Here, we studied a SIVmac239-infected elite controller rhesus macaque with a 1,000-fold spontaneous increase in plasma viral load that preceded disease progression and death from AIDS-related complications. We sequenced the viral genome pre- and post-breakthrough and demonstrate that CD8+ T cells drove the majority of the amino acid substitutions outside of Env. However, within a region of Gag p27CA targeted only by CD4+ T cells, we identified a unique post-breakthrough mutation, Gag D205E, which abrogated CD4+ T cell recognition. Further, we demonstrate that the Gag p27CA-specific CD4+ T cells exhibited cytolytic activity and that SIV bearing the Gag D205E mutation escapes this CD4+ T cell effector function ex vivo.

Conclusions

Cumulatively, these results confirm the importance of virus specific CD8+ T cells and demonstrate that CD4+ T cells can also exert significant selective pressure on immunodeficiency viruses in vivo during low-level viral replication. These results also suggest that further studies of CD4+ T cell escape should focus on cases of elite control with spontaneous viral breakthrough.
Peripheral Nerve Injury Increases Glutamate-Evoked Calcium Mobilization in Adult Spinal Cord Neurons
Authors: Doolen Suzanne , Blake Camille B , Smith Bret N , Taylor Bradley K
Published: November 2012

Background:

Central sensitization in the spinal cord requires glutamate receptor activation and intracellular Ca2+ mobilization. We used Fura-2 AM bulk loading of mouse slices together with wide-field Ca2+ imaging to measure glutamate-evoked increases in extracellular Ca2+ to test the hypotheses that: 1. Exogenous application of glutamate causes Ca2+ mobilization in a preponderance of dorsal horn neurons within spinal cord slices taken from adult mice; 2. Glutamate-evoked Ca2+ mobilization is associated with spontaneous and/or evoked action potentials; 3. Glutamate acts at glutamate receptor subtypes to evoked Ca2+ transients; and 4. The magnitude of glutamate-evoked Ca2+ responses increases in the setting of peripheral neuropathic pain.

Results:

Bath-applied glutamate robustly increased [Ca2+]i in 14.4 ± 2.6 cells per dorsal horn within a 440 × 330 um field-of-view, with an average time-to-peak of 27 s and decay of 112 s. Repeated application produced sequential responses of similar magnitude, indicating the absence of sensitization, desensitization or tachyphylaxis. Ca2+ transients were glutamate concentration-dependent with a Kd = 0.64 mM. Ca2+ responses predominantly occurred on neurons since: 1) Over 95% of glutamate-responsive cells did not label with the astrocyte marker, SR-101; 2) 62% of fura-2 AM loaded cells exhibited spontaneous action potentials; 3) 75% of cells that responded to locally-applied glutamate with a rise in [Ca2+]i also showed a significant increase in AP frequency upon a subsequent glutamate exposure; 4) In experiments using simultaneous on-cell recordings and Ca2+ imaging, glutamate elicited a Ca2+ response and an increase in AP frequency. AMPA/kainate (CNQX)- and AMPA (GYKI 52466)-selective receptor antagonists significantly attenuated glutamate-evoked increases in [Ca2+]i, while NMDA (AP-5), kainate (UBP-301) and class I mGluRs (AIDA) did not. Compared to sham controls, peripheral nerve injury significantly decreased mechanical paw withdrawal threshold and increased glutamate-evoked Ca2+ signals.

Conclusions:

Bulk-loading fura-2 AM into spinal cord slices is a successful means for determining glutamate-evoked Ca2+ mobilization in naïve adult dorsal horn neurons. AMPA receptors mediate the majority of these responses. Peripheral neuropathic injury potentiates Ca2+ signaling in dorsal horn.
PhenoPhyte: a flexible affordable method to quantify 2D phenotypes from imagery
Authors: Green Jason M , Appel Heidi , Rehrig Erin MacNeal , Harnsomburana Jaturon , Chang Jia-Fu , Balint-Kurti Peter , Shyu Chi-Ren
Published: November 2012

Background

Accurate characterization of complex plant phenotypes is critical to assigning biological functions to genes through forward or reverse genetics. It can also be vital in determining the effect of a treatment, genotype, or environmental condition on plant growth or susceptibility to insects or pathogens. Although techniques for characterizing complex phenotypes have been developed, most are not cost effective or are too imprecise or subjective to reliably differentiate subtler differences in complex traits like growth, color change, or disease resistance.

Results

We designed an inexpensive imaging protocol that facilitates automatic quantification of two-dimensional visual phenotypes using computer vision and image processing algorithms applied to standard digital images. The protocol allows for non-destructive imaging of plants in the laboratory and field and can be used in suboptimal imaging conditions due to automated color and scale normalization. We designed the web-based tool PhenoPhyte for processing images adhering to this protocol and demonstrate its ability to measure a variety of two-dimensional traits (such as growth, leaf area, and herbivory) using images from several species (Arabidopsis thaliana and Brassica rapa). We then provide a more complicated example for measuring disease resistance of Zea mays to Southern Leaf Blight.

Conclusions

PhenoPhyte is a new cost-effective web-application for semi-automated quantification of two-dimensional traits from digital imagery using an easy imaging protocol. This tool’s usefulness is demonstrated for a variety of traits in multiple species. We show that digital phenotyping can reduce human subjectivity in trait quantification, thereby increasing accuracy and improving precision, which are crucial for differentiating and quantifying subtle phenotypic variation and understanding gene function and/or treatment effects.
Quetiapine-induced sleep-related eating disorder-like behavior: a case series
Authors: Tamanna Sadeka , Ullah M Iftekhar , Pope Chelle R , Holloman Garland , Koch Christian A
Published: November 2012

Introduction

Somnambulism or sleepwalking is a disorder of arousal from non-rapid eye movement sleep. The prevalence of sleep-related eating disorder has been found to be approximately between 1% and 5% among adults. Many cases of medication-related somnambulism and sleep-related eating disorder-like behavior have been reported in the literature. Quetiapine, an atypical antipsychotic medication, has been associated with somnambulism but has not yet been reported to be associated with sleep-related eating disorder.

Case presentation

Case 1 is a 51-year-old obese African American male veteran with a body mass index of 34.11kg/m2and severe sleep apnea who has taken 150mg of quetiapine at bedtime for more than one year for depression. He developed sleepwalking three to four nights per week which resolved after stopping quetiapine while being compliant with bi-level positive pressure ventilation therapy. At one year follow-up, his body mass index was 32.57kg/m2.

Case 2 is a 50-year-old African American female veteran with a body mass index of 30.5kg/m2and mild sleep apnea who has taken 200mg of quetiapine daily for more than one year for depression. She was witnessed to sleepwalk three nights per week which resolved after discontinuing quetiapine while being treated with continuous positive airway pressure. At three months follow-up, her body mass index was 29.1kg/m2.

Conclusion

These cases illustrate that quetiapine may precipitate complex motor behavior including sleep-related eating disorder and somnambulism in susceptible patients. Atypical antipsychotics are commonly used in psychiatric and primary care practice, which means the population at risk of developing parasomnia may often go unrecognized. It is important to recognize this potential adverse effect of quetiapine and, to prevent injury and worsening obesity, discuss this with the patients who are prescribed these medications.
Early-age feed restriction affects viability and gene expression of satellite cells isolated from the gastrocnemius muscle of broiler chicks
Authors: Li Yue , Yang Xiaojing , Ni Yingdong , Decuypere Eddy , Buyse Johan , Everaert Nadia , Grossmann Roland , Zhao Ruqian
Published: November 2012

Background

Muscle growth depends on the fusion of proliferate satellite cells to existing myofibers. We reported previously that 0–14 day intermittent feeding led to persistent retardation in myofiber hypertrophy. However, how satellite cells respond to such nutritional insult has not been adequately elucidated.

Results

One-day-old broiler chicks were allocated to control (Con, ad libitum feeding), intermittent feeding (IF, feed provided on alternate days) and re-feeding (RF, 2 days ad libitum feeding after 12 days of intermittent feeding) groups. Chickens were killed on Day 15 and satellite cells were isolated. When cultured, satellite cells from the IF group demonstrated significant retardation in proliferation and differentiation potential, while RF partly restored the proliferation rate and differentiation potential of the satellite cells. Significant up-regulation of insulin like growth factor I receptor (IGF-IR) (P< 0.05) and thyroid hormone receptor α (TRα) (P< 0.05), and down-regulation of growth hormone receptor (GHR) (P< 0.01) and IGF-I (P< 0.01) mRNA expression was observed in freshly isolated IF satellite cells when compared with Con cells. In RF cells, the mRNA expression of IGF-I was higher (P< 0.05) and of TRα was lower (P< 0.01) than in IF cells, suggesting that RF restored the mRNA expression of TRα and IGF-I, but not of GHR and IGF-IR. The Bax/Bcl-2 ratio tended to increase in the IF group, which was reversed in the RF group (P< 0.05), indicating that RF reduced the pro-apoptotic influence of IF. Moreover, no significant effect of T3 was detected on cell survival in IF cells compared with Con (P<0.001) or RF (P< 0.05) cells.

Conclusions

These data suggest that early-age feed restriction inhibits the proliferation and differentiation of satellite cells, induces changes in mRNA expression of the GH/IGF-I and thyroid hormone receptors in satellite cells, as well as blunted sensitivity of satellite cells to T3, and that RF partially reverses these effects. Thus, a moderate nutritional strategy for feed restriction should be chosen in early chick rearing systems.
Automatic stabilization and discretionary fiscal policy in the financial crisis
Authors: Dolls Mathias , Fuest Clemens , Peichl Andreas
Published: November 2012

This paper investigates the relationship between the magnitude of automatic stabilizers in the tax and transfer systems of 19 EU countries and the US, and discretionary fiscal stimulus packages passed by these countries during the recent economic crisis. In particular, we ask whether countries with larger automatic stabilizers have enacted smaller discretionary fiscal stimulus programs. Our results support this hypothesis. Our findings also suggest that social transfers, in particular the rather generous systems of unemployment insurance in Europe, play a key role for the stabilization of disposable incomes and explain a large part of the difference in automatic stabilizers between Europe and the US.
Randomized Trial of Myeloablative Conditioning Regimens: Busulfan Plus Cyclophosphamide Versus Busulfan Plus Fludarabine
Authors: Lee Je-Hwan , Joo Young-Don , Kim Hawk , Ryoo Hun Mo , Kim Min Kyoung , Lee Gyeong-Won , Lee Jung-Hee , Lee Won-Sik , Park Jae-Hoo , Bae Sung-Hwa , Hyun Myung Soo , Kim Dae-Young , Kim Sung-Doo , Min Young Joo , Lee Kyoo-Hyung
Published: November 2012

Purpose

We conducted a phase III randomized clinical trial to compare two myeloablative conditioning regimens for allogeneic hematopoietic cell transplantation (HCT) in patients with leukemia and myelodysplastic syndrome.

Patients and Methods

After randomization, 64 patients received busulfan (3.2 mg/kg per day × 4 days) plus cyclophosphamide (60 mg/kg per day × 2 days; BuCy), and 62 patients received busulfan (same dose and schedule) plus fludarabine (30 mg/m2per day × 5 days; BuFlu).

Results

The median age was 41 years (range, 17 to 59 years). Five patients in the BuFlu arm experienced graft failure (primary, n = 1; secondary, n = 4). At 4 weeks after HCT, the median percentage of recipient hematopoietic chimerism was significantly greater in the BuFlu arm (0% v 5.5%; P < .001), and complete donor chimerism was greater in the BuCy arm (97.2% v 44.4%; P < .001). Severe (grade 3 or higher) infection and gastrointestinal adverse events were significantly more common in the BuCy arm, but the frequencies of hepatic adverse events were similar in the two arms. Nonrelapse mortality was similar in the two arms, but the BuCy arm had better overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS; OS at 2 years, 67.4% v 41.4%, P = .014; RFS, 74.7% v 54.9%, P = .027; EFS, 60.7% v 36.0%, P = .014).

Conclusion

Our results indicate that the BuFlu regimen is not a suitable replacement for the BuCy regimen in young adults who are eligible for myeloablative conditioning therapy for allogeneic HCT.
Use of Research Biopsies in Clinical Trials: Are Risks and Benefits Adequately Discussed?
Authors: Overman Michael J. , Modak Janhavi , Kopetz Scott , Murthy Ravi , Yao James C. , Hicks Marshall E. , Abbruzzese James L. , Tam Alda L.
Published: November 2012

Purpose

Although the incorporation of research biopsies into clinical trials is increasing, limited information is available about how study protocols and informed consents integrate and describe their use.

Methods

All therapeutic clinical trials in which image-guided research biopsies were performed from January 1, 2005, to October 1, 2010, were identified from an interventional radiology database. Data from study protocols and informed consents were extracted and analyzed. Procedural complications were recorded.

Results

A total of 57 clinical trials were identified, of which 38 (67%) contained at least one mandatory biopsy. The analysis of the research biopsy tumor tissue was a study end point in 95% of trials. The primary indication for a research biopsy was for integral biomarker analysis in 32% and for correlative science in 68% of trials. A statistical analytic plan for the correlative science research biopsy tumor tissue was mentioned in 26%, described as exploratory in 51%, and not mentioned in 23% of trials. For studies with mandatory biopsies, biopsy was an eligibility criterion in 71% of trials, and a statistical justification for the research biopsy sample size was present in 50% of trials. A total of 745 research biopsies were performed on 576 patients. Overall and major complication rates were 5.2% (39 of 745 biopsies) and 0.8% (six of 745 biopsies), respectively. Complication rates for intrathoracic and abdominal/pelvic solid organ biopsies were 17.1% (36 of 211 biopsies) and 1.6% (three of 189 biopsies), respectively. Site-stratified research biopsy–related risks were discussed in five consents.

Conclusion

A better representation of the risks and benefits of research biopsies in study protocols and informed consents is needed.