bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Intonation and Valence on Objective and Subjective Attention Capture by Auditory Alarms
Authors: Ljungberg Jessica K. , Parmentier Fabrice 
Published: March 2012

Objective: The objective was to study the involuntary capture of attention by spoken words varying in intonation and valence. Background: In studies of verbal alarms, the propensity of alarms to capture attention has been primarily assessed with the use of subjective ratings of their perceived urgency. Past studies suggest that such ratings vary with the alarms’ spoken urgency and content. Method: We measured attention capture by spoken words varying in valence (negative vs. neutral) and intonation (urgently vs. nonurgently spoken) through subjective ratings and behavioral measures. The key behavioral measure was the response latency to visual stimuli in the presence of spoken words breaking away from the periodical repetition of a tone. Results: The results showed that all words captured attention relative to a baseline standard tone but that this effect was partly counteracted by a relative speeding of responses for urgently compared with nonurgently spoken words. Word valence did not affect behavioral performance. Rating data showed that both intonation and valence increased significantly perceived urgency and attention grabbing without any interaction. Conclusion: The data suggest a congruency between subjective ratings and behavioral performance with respect to spoken intonation but not valence. Application: This study demonstrates the usefulness and feasibility of objective measures of attention capture to help design efficient alarm systems.
Population Pharmacokinetics and Pharmacodynamics of Gabapentin After Administration of Gabapentin Enacarbil
Authors: Lal Ritu , Sukbuntherng Juthamas , Luo Wendy , Tovera James , Lassauzet Marie Liesse , Cundy Kenneth C. 
Published: March 2012

AbstractGabapentin enacarbil (GEn) is an actively transported prodrug of gabapentin that provides sustained dose‐proportional exposure to gabapentin and predictable bioavailability. Gabapentin enacarbil is approved by the US Food and Drug Administration for the treatment of moderate‐to‐severe primary restless legs syndrome (RLS) in adults. Using plasma gabapentin concentration data obtained after administration of GEn in 12 phase 1 to 3 GEn studies in healthy adults or patients with RLS (dose range, 300‐2400 mg/d), a population pharmacokinetic (PK) model was developed by nonlinear mixed‐effect modeling using NONMEM. Data were similar in subjects with and without RLS. Population PK‐pharmacodynamic (PD) models were evaluated using gabapentin exposure and change from baseline in investigator‐ or patient‐rated Clinical Global Impression of Improvement (CGI‐I) or International Restless Legs Scale (IRLS) total score. Potential PK‐PD models for sleep outcomes and safety parameters were also explored. The CGI‐I response increased with increasing GEn dose, whereas the IRLS total score was similar at all exposures tested. Early adverse events of dizziness or somnolence/sedation were more frequent for GEn 600 mg than higher doses; however, this is confounded by the fact that all subjects received the 600‐mg dose for 3 days prior to titration to higher dosages.
Mapping regional grey and white matter atrophy in relapsing–remitting multiple sclerosis
Authors: Riccitelli Gianna , Rocca Maria A , Pagani Elisabetta , Martinelli Vittorio , Radaelli Marta , Falini Andrea , Comi Giancarlo , Filippi Massimo 
Published: March 2012

Objective: We aimed to investigate the regional distribution of grey matter (GM) and white matter (WM) atrophy in patients with relapsing–remitting (RR) MS and their relationship with gender, clinical findings, and T2 lesions. Methods: Clinical and magnetic resonance imaging assessments were obtained from 78 patients with RRMS and 88 controls. GM and WM atrophy were estimated using voxel-based morphometry (SPM8). Results: Patients with RRMS experienced atrophy of the deep GM nuclei, and several cortical regions mainly located in the fronto-parietal lobes. WM atrophy involved posterior regions of the brain, including the cerebellum and brainstem. Compared with men, affected women showed atrophy of several WM tracts, while gender did not impact GM atrophy. Disease duration > 5 years was associated with atrophy of the thalami and inferior frontal gyrus, while WM atrophy was already prominent in patients with disease duration ≤ 5 years. Expanded Disability Status Scale score > 3.0 was associated with diffuse WM atrophy and basal ganglia and precentral gyrus atrophy. T2 lesions were marginally associated to focal atrophy. Discussion: In RRMS, GM and WM atrophy have distinct patterns of regional distribution, with a sparing of GM infratentorial regions. Gender, disease duration and disability affect differently the topography of GM/WM atrophy, while T2 lesions play a modest role.
The DEAH-box helicase RHAU is an essential gene and critical for mouse hematopoiesis
Authors: Lai Janice Ching , Ponti Svetlana , Pan Dejing , Kohler Hubertus , Skoda Radek C. , Matthias Patrick , Nagamine Yoshikuni 
Published: March 2012

AbstractThe DEAH helicase RHAU (alias DHX36, G4R1) is the only helicase shown to have G-quadruplex (G4)–RNA resolvase activity and the major source of G4-DNA resolvase activity. Previous report showed RHAU mRNA expression to be elevated in human lymphoid and CD34+ BM cells, suggesting a potential role in hematopoiesis. Here, we generated a conditional knockout of the RHAU gene in mice. Germ line deletion of RHAU led to embryonic lethality. We then targeted the RHAU gene specifically in the hematopoiesis system, using a Cre-inducible system in which an optimized variant of Cre recombinase was expressed under the control of the Vav1 promoter. RHAU deletion in hematopoietic system caused hemolytic anemia and differentiation defect at the proerythroblast stage. The partial differentiation block of proerythroblasts was because of a proliferation defect. Transcriptome analysis of RHAU knockout proerythroblasts showed that a statistically significant portion of the deregulated genes contain G4 motifs in their promoters. This suggests that RHAU may play a role in the regulation of gene expression that relies on its G4 resolvase activity.
The endogenous proteoglycan-degrading enzyme ADAMTS-4 promotes functional recovery after spinal cord injury
Authors: Tauchi Ryoji , Imagama Shiro , Natori Takamitsu , Ohgomori Tomohiro , Muramoto Akio , Shinjo Ryuichi , Matsuyama Yukihiro , Ishiguro Naoki , Kadomatsu Kenji 
Published: March 2012

Abstract

Background
Chondroitin sulfate proteoglycans are major inhibitory molecules for neural plasticity under both physiological and pathological conditions. The chondroitin sulfate degrading enzyme chondroitinase ABC promotes functional recovery after spinal cord injury, and restores experience-dependent plasticity, such as ocular dominance plasticity and fear erasure plasticity, in adult rodents. These data suggest that the sugar chain in a proteoglycan moiety is essential for the inhibitory activity of proteoglycans. However, the significance of the core protein has not been studied extensively. Furthermore, considering that chondroitinase ABC is derived from bacteria, a mammalian endogenous enzyme which can inactivate the proteoglycans' activity is desirable for clinical use.

Methods
The degradation activity of ADAMTS-4 was estimated for the core proteins of chondroitin sulfate proteoglycans, that is, brevican, neurocan and phosphacan. To evaluate the biological significance of ADMATS-4 activity, an in vitro neurite growth assay and an in vivo neuronal injury model, spinal cord contusion injury, were employed.

Results
ADAMTS-4 digested proteoglycans, and reversed their inhibition of neurite outgrowth. Local administration of ADAMTS-4 significantly promoted motor function recovery after spinal cord injury. Supporting these findings, the ADAMTS-4-treated spinal cord exhibited enhanced axonal regeneration/sprouting after spinal cord injury.

Conclusions
Our data suggest that the core protein in a proteoglycan moiety is also important for the inhibition of neural plasticity, and provides a potentially safer tool for the treatment of neuronal injuries.
Leukotrienes inhibit early stages of HIV-1 infection in monocyte-derived microglia-like cells
Authors: Bertin Jonathan , Barat Corinne , Bélanger Dave , Tremblay Michel J 
Published: March 2012

AbstractBackgroundMicroglia are one of the main cell types to be productively infected by HIV-1 in the central nervous system (CNS). Leukotriene B4(LTB4) and cysteinyl-leukotrienes such as LTC4are some of the proinflammatory molecules produced in infected individuals that contribute to neuroinflammation. We therefore sought to investigate the role of leukotrienes (LTs) in HIV-1 infection of microglial cells.MethodsTo evaluate the role of LTs on HIV-1 infection in the CNS, monocyte-derived microglial-like cells (MDMis) were utilized in this study. Leukotriene-treated MDMis were infected with either fully replicative brain-derived HIV-1 isolates (YU2) or R5-tropic luciferase-encoding particles in order to assess viral production and expression. The efficacy of various steps of the replication cycle was evaluated by means of p24 quantification by ELISA, luciferase activity determination and quantitative real-time polymerase chain reaction (RT-PCR).ResultsWe report in this study that virus replication is reduced upon treatment of MDMis with LTB4and LTC4. Additional experiments indicate that these proinflammatory molecules alter the pH-independent entry and early post-fusion events of the viral life cycle. Indeed, LT treatment induced a diminution in integrated proviral DNA while reverse-transcribed viral products remained unaffected. Furthermore, decreased C-C chemokine receptor type 5 (CCR5) surface expression was observed in LT-treated MDMis. Finally, the effect of LTs on HIV-1 infection in MDMis appears to be mediated partly via a signal transduction pathway involving protein kinase C.ConclusionsThese data show for the first time that LTs influence microglial cell infection by HIV-1, and may be a factor in the control of viral load in the CNS.
Molecular and epigenetic analysis of the fragile histidine triad tumour suppressor gene in equine sarcoids
Authors: Strazzullo Maria , Corteggio Annunziata , Altamura Gennaro , Francioso Romina , Roperto Franco , D'Esposito Maurizio , Borzacchiello Giuseppe 
Published: March 2012

Abstract

Background
Sarcoids are peculiar equine benign tumours. Their onset is associated with Bovine Papillomavirus type -1 or -2 (BPV-1/2) infection. Little is known about the molecular interplay between viral infection and neoplastic transformation. The data regarding papillomavirus infections in human species show the inactivation of a number of tumour suppressor genes as basic mechanism of transformation. In this study the putative role of the tumour suppressor gene Fragile Histidine Triad (FHIT) in sarcoid tumour was investigated in different experimental models. The expression of the oncosuppressor protein was assessed in normal and sarcoid cells and tissue.

Results
Nine paraffin embedded sarcoids and sarcoid derived cell lines were analysed for the expression of FHIT protein by immunohistochemistry, immunofluorescence techniques and western blotting. These analyses revealed the absence of signal in seven out of nine sarcoids. The two sarcoid derived cell lines too showed a reduced signal of the protein. To investigate the causes of the altered protein expression, the samples were analysed for the DNA methylation profile of the CpG island associated with the FHIT promoter. The analysis of the 32 CpGs encompassing the region of interest showed no significative differential methylation profile between pathological tissues and cell lines and their normal counterparts.

Conclusion
This study represent a further evidence of the role of a tumour suppressor gene in equine sarcoids and approaches the epigenetic regulation in this well known equine neoplasm. The data obtained in sarcoid tissues and sarcoid derived cell lines suggest that also in horse, as in humans, there is a possible involvement of the tumour suppressor FHIT gene in BPV induced tumours. DNA methylation seems not to be involved in the gene expression alteration. Further studies are needed to understand the basic molecular mechanisms involved in reduced FHIT expression.
Soil-transmitted helminth infections and physical fitness in school-aged Bulang children in southwest China: results from a cross-sectional survey
Authors: Yap Peiling , Du Zun-Wei , Chen Ran , Zhang Li-Ping , Wu Fang-Wei , Wang Jian , Wang Xue-Zhong , Zhou Hui , Zhou Xiao-Nong , Utzinger Jürg , Steinmann Peter 
Published: March 2012

Abstract

Background
Chronic soil-transmitted helminth (STH) infections have been associated with reduced physical fitness, but available evidence is limited. The aim of this cross-sectional survey was to assess the feasibility of measuring children's physical fitness and to relate it to STH infections. Our study was carried out among school-aged children of the Bulang ethnic group in rural southwest People's Republic of China (P.R. China). Standardized, quality-controlled methods were employed to determine STH infections (Kato-Katz technique), haemoglobin levels, anthropometry (body weight and height) and physical fitness (20-m shuttle run test).

Results
A compliance of 87% suggested good acceptance of the methods used. Among 69 children with complete data records, infection prevalence of Trichuris trichiura, Ascaris lumbricoides and hookworm were 81%, 44% and 6%, respectively. The maximum volume of oxygen that can be utilized within 1 min during exhaustive exercise (VO2 max estimate) of T. trichiura-infected children was 1.94 ml kg-1 min-1 lower than that of their non-infected counterparts (P = 0.005). Until exhaustion, T. trichiura-infected children had completed 6.14 20-m laps less (P = 0.004). Additionally, the mean VO2 max estimate of stunted children was lowered by 1.63 ml kg-1 min-1 (P = 0.002) and they completed 5.32 20-m laps less (P = 0.001) compared to children of normal stature. No significant association between stunting and infection with any STH species could be established.

Conclusions
Implementation of physical fitness tests in rural, resource-constraint settings is feasible. The physical fitness of children who are stunted or infected with STHs, particularly T. trichiura, is significantly impaired. We have launched a larger study and will determine the dynamics of school-aged children's physical fitness over a 7-month period after administration of anthelminthic drugs.
Novel mutatıons and diverse clinical phenotypes in recombınase-activating gene 1 deficiency
Authors: Kutukculer Necil , Gulez Nesrin , Karaca Neslihan Edeer , Aksu Guzide , Berdeli Afig 
Published: March 2012

Abstract

Background
Severe combined immunodeficiency is within a heterogeneous group of inherited defects throughout the development of T- and/or B-lymphocytes. Mutations in recombinase-activating genes 1 or 2 (RAG1/2) represent approximately 10% of all SCID cases. RAG1/2 are essential for V(D)J rearrangement of the B- and T-cell receptors.

Objectives
The aim of this study was to review clinical, immunological and molecular findings of Turkish SCID patients with RAG1 defects and to draw attention to novel mutations, genotype-phenotype correlations and the high rate of BCG infections within this group.

Methods
Eleven patients (F/M: 6/5) were included. Molecular, immunological and clinical data were evaluated.

Results
Five patients were classified as T-B-NK + SCID, four patients as T + B-NK + SCID (two of these patients were diagnosed as classical Omenn syndrome) and two patients as T + B + NK + SCID with respect to clinical presentations and immunological data. Mean age of the whole study group, mean age at onset of symptoms and mean age at diagnosis were: 33.0 ± 42.8, 3.1 ± 3.3 and 10.4 ± 13.5 months, respectively. Consanguinity rate was 54%. Some novel mutations were found in RAG1 gene in addition to previously reported mutations. Genotype-phenotype correlation was not significantly apparent in most of the cases. BCG infection was observed in 36.4% of patients (two BCG-osis and two BCG-itis).

Conclusion
Epigenetic factors such as compound genetic defects, enviromental factors, and exposure to recurrent infections may modify phenotypical characteristics of RAG deficiencies. Inoculation of live vaccines such as BCG should be postponed until primary immunodeficiency disease is excluded with appropriate screening tests in suspected cases.
Coronary versus carotid blood flow and coronary perfusion pressure in a pig model of prolonged cardiac arrest treated by different modes of venoarterial ECMO and intraaortic balloon counterpulsation
Authors: Bělohlávek Jan , Mlček Mikuláš , Huptych Michal , Svoboda Tomáš , Havránek Štěpán , Ošt'ádal Petr , Bouček Tomáš , Kovárník Tomáš , Mlejnský František , Mrázek Vratislav , Bělohlávek Marek , Aschermann Michael , Linhart Aleš , Kittnar Otomar 
Published: March 2012

Abstract
Introduction
Extracorporeal membrane oxygenation (ECMO) is increasingly used in cardiac arrest (CA). Adequacy of carotid and coronary blood flows (CaBF, CoBF) and coronary perfusion pressure (CoPP) in ECMO treated CA is not well established. This study compares femoro-femoral (FF) to femoro-subclavian (FS) ECMO and intraaortic balloon counterpulsation (IABP) contribution based on CaBF, CoBF, CoPP, myocardial and brain oxygenation in experimental CA managed by ECMO.

Methods
In 11 female pigs (50.3 ± 3.4 kg), CA was randomly treated by FF versus FS ECMO ± IABP. Animals under general anesthesia had undergone 15 minutes of ventricular fibrillation (VF) with ECMO flow of 5 to 10 mL/kg/min simulating low-flow CA followed by continued VF with ECMO flow of 100 mL/kg/min. CaBF and CoBF were measured by a Doppler flow wire, cerebral and peripheral oxygenation by near infrared spectroscopy. CoPP, myocardial oxygen metabolism and resuscitability were determined.

Results
CaBF reached values > 80% of baseline in all regimens. CoBF > 80% was reached only by the FF ECMO, 90.0% (66.1, 98.6). Addition of IABP to FF ECMO decreased CoBF to 60.7% (55.1, 86.2) of baseline, P = 0.004. FS ECMO produced 70.0% (49.1, 113.2) of baseline CoBF, significantly lower than FF, P = 0.039. Addition of IABP to FS did not change the CoBF; however, it provided significantly higher flow, 76.7% (71.9, 111.2) of baseline, compared to FF + IABP, P = 0.026. Both brain and peripheral regional oxygen saturations decreased after induction of CA to 23% (15.0, 32.3) and 34% (23.5, 34.0), respectively, and normalized after ECMO institution. For brain saturations, all regimens reached values exceeding 80% of baseline, none of the comparisons between respective treatment approaches differed significantly. After a decline to 15 mmHg (9.5, 20.8) during CA, CoPP gradually rose with time to 68 mmHg (43.3, 84.0), P = 0 .003, with best recovery on FF ECMO. Resuscitability of the animals was high, both 5 and 60 minutes return of spontaneous circulation occured in eight animals (73%).

Conclusions
In a pig model of CA, both FF and FS ECMO assure adequate brain perfusion and oxygenation. FF ECMO offers better CoBF than FS ECMO. Addition of IABP to FF ECMO worsens CoBF. FF ECMO, more than FS ECMO, increases CoPP over time.
Alveolar macrophages in diabetes: friends or foes?
Authors: Sunahara Karen K S , Martins Joilson O 
Published: March 2012

ABSTRACTAMs constitute an important bridge between innate and adaptive immunity. AMs patrol the lungs against pathogens, remove senescent cells, and help repair tissue. AM function is altered in many diseases, including DM, where AM abnormal immune responses may worsen infections or lead to exacerbation of inflammatory reactions. In vivo experimental models have greatly contributed to our knowledge of AM function. Studies have shown that during hyperglycemic states, the phagocytic function of AMs and the expression of adhesion molecules may be altered, interfering with the recruitment of immune cells to the inflammatory site. Insulin treatment seems to recover the normal function of impaired AMs. However, much research is still needed to characterize AMs and to better understand their role in inflammation and infection, particularly in diabetic patients. In this review, we attempt to explore recently accumulated knowledge about AM function and how this function is deficient in DM. Additionally, AM polarization is compared briefly with that of T cells, and this may interfere with how immune response is driven. This review discusses how impaired AMs lead to an aberrant immune response that contributes to worsening infection and autoimmunity, opening up discussion for future work in the field.
Extending Oncology Clinical Services to Rural Areas of Texas Via Teleoncology
Authors: Sharma Jivesh J. , Gross Gary , Sharma Poonam 
Published: March 2012

Abstracts Purpose: For patients in rural Texas, accessing cancer specialists is quite challenging. Texas has many remote areas without community-based cancer care, requiring patients to travel long distances for specialized cancer professional consultations and services. An anticipated shortage of medical oncology expertise will exacerbate this situation. The advent of telemedicine tools has created an opportunity to easily extend specialized cancer services to underserved populations of patients with cancer in Texas. However, more research is needed to explore how well telemedicine tools will be accepted and used by both patients and oncologists alike. Data suggesting that teleoncology services are well accepted and liked by patients and health care professionals would provide a basis for expanding this method of delivering care. If effective, telemedicine tools could help patients with cancer in rural Texas, and throughout the United States, access the same quality of cancer care as their counterparts living in urban areas. Methods: This pilot study will compare the effectiveness and reliability of remote oncologic clinical evaluations conducted via a telemedicine application with the traditional method of onsite evaluations in a private practice setting in rural East Texas. Patient and physician satisfaction with the clinical consultations and their perceptions of the telemedicine application will be assessed using a questionnaire administered at the conclusion of the clinical meetings. Results: Initial results indicate high patient and physician satisfaction scores as well as high reliability and adequacy of the equipment and technology being used. Conclusion: Both patients and physicians are highly satisfied with the quality of teleoncology examinations and express openness to this method of delivering care.