bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemokine CCL2 and its receptor CCR2 in the medullary dorsal horn are involved in trigeminal neuropathic pain
Authors: Zhang Zhi-Jun , Dong Yu-Lin , Lu Ying , Cao Su , Zhao Zhi-Qi , Gao Yong-Jing 
Published: July 2012

AbstractBackgroundNeuropathic pain in the trigeminal system is frequently observed in clinic, but the mechanisms involved are largely unknown. In addition, the function of immune cells and related chemicals in the mechanism of pain has been recognized, whereas few studies have addressed the potential role of chemokines in the trigeminal system in chronic pain. The present study was undertaken to test the hypothesis that chemokine C-C motif ligand 2 (CCL2)-chemokine C-C motif receptor 2 (CCR2) signaling in the trigeminal nucleus is involved in the maintenance of trigeminal neuropathic pain.MethodsThe inferior alveolar nerve and mental nerve transection (IAMNT) was used to induce trigeminal neuropathic pain. The expression of ATF3, CCL2, glial fibrillary acidic protein (GFAP), and CCR2 were detected by immunofluorescence histochemical staining and western blot. The cellular localization of CCL2 and CCR2 were examined by immunofluorescence double staining. The effect of a selective CCR2 antagonist, RS504393 on pain hypersensitivity was checked by behavioral testing.ResultsIAMNT induced persistent (>21 days) heat hyperalgesia of the orofacial region and ATF3 expression in the mandibular division of the trigeminal ganglion. Meanwhile, CCL2 expression was increased in the medullary dorsal horn (MDH) from 3 days to 21 days after IAMNT. The induced CCL2 was colocalized with astroglial marker GFAP, but not with neuronal marker NeuN or microglial marker OX-42. Astrocytes activation was also found in the MDH and it started at 3 days, peaked at 10 days and maintained at 21 days after IAMNT. In addition, CCR2 was upregulated by IAMNT in the ipsilateral medulla and lasted for more than 21 days. CCR2 was mainly colocalized with NeuN and few cells were colocalized with GFAP. Finally, intracisternal injection of CCR2 antagonist, RS504393 (1, 10 μg) significantly attenuated IAMNT-induced heat hyperalgesia.ConclusionThe data suggest that CCL2-CCR2 signaling may be involved in the maintenance of orofacial neuropathic pain via astroglial–neuronal interaction. Targeting CCL2-CCR2 signaling may be a potentially important new treatment strategy for trigeminal neuralgia.
Complement receptor-3 negatively regulates the phagocytosis of degenerated myelin through tyrosine kinase Syk and cofilin
Authors: Hadas Smadar , Spira Maya , Hanisch Uwe-Karsten , Reichert Fanny , Rotshenker Shlomo 
Published: July 2012

AbstractBackgroundIntact myelin, which normally surrounds axons, breaks down in Wallerian degeneration following axonal injury and during neurodegenerative diseases such as multiple sclerosis. Clearance of degenerated myelin by phagocytosis is essential since myelin impedes repair and exacerbates damage. CR3 (complement receptor-3) is a principal phagocytic receptor in myelin phagocytosis. We studied how tyrosine kinase Syk (spleen tyrosine kinase) and cofilin control phagocytosis of degenerated myelin by CR3 in microglia and macrophages. Syk is a non-receptor tyrosine kinase that CR3 recruits to convey cellular functions. Cofilin is an actin-depolymerizing protein that controls F-actin (filamentous actin) remodeling (i.e., disassembly and reassembly) by shifting between active unphosphorylated and inactive phosphorylated states.ResultsSyk was continuously activated during prolonged phagocytosis. Phagocytosis increased when Syk activity and expression were reduced, suggesting that normally Syk down regulates CR3-mediated myelin phagocytosis. Levels of inactive p-cofilin (phosphorylated cofilin) decreased transiently during prolonged phagocytosis. In contrast, p-cofilin levels decreased continuously when Syk activity and expression were continuously reduced, suggesting that normally Syk advances the inactive state of cofilin. Observations also revealed inverse relationships between levels of phagocytosis and levels of inactive p-cofilin, suggesting that active unphosphorylated cofilin advances phagocytosis. Active cofilin could advance phagocytosis by promoting F-actin remodeling, which supports the production of membrane protrusions (e.g., filopodia), which, as we also revealed, are instrumental in myelin phagocytosis.ConclusionsCR3 both activates and downregulates myelin phagocytosis at the same time. Activation was previously documented. We presently demonstrate that downregulation is mediated through Syk, which advances the inactive phosphorylated state of cofilin. Self-negative control of phagocytosis by the phagocytic receptor can be useful in protecting phagocytes from excessive phagocytosis (i.e., “overeating”) during extended exposure to particles that are destined for ingestion.
The Majority of Dorsal Spinal Cord Gastrin Releasing Peptide is Synthesized Locally Whereas Neuromedin B is Highly Expressed in Pain- and Itch-Sensing Somatosensory Neurons
Authors: Fleming Michael S , Ramos Daniel , Han Seung Baek , Zhao Jianyuan , Son Young-Jin , Luo Wenqin 
Published: July 2012

Background: Itch is one of the major somatosensory modalities. Some recent findings have proposed that gastrin releasing peptide (Grp) is expressed in a subset of dorsal root ganglion (DRG) neurons and functions as a selective neurotransmitter for transferring itch information to spinal cord interneurons. However, expression data from public databases and earlier literatures indicate that Grp mRNA is only detected in dorsal spinal cord (dSC) whereas its family member neuromedin B ( Nmb) is highly expressed in DRG neurons. These contradictory results argue that a thorough characterization of the expression of Grp and Nmb is warranted. Findings: Grp mRNA is highly expressed in dSC but is barely detectable in DRGs of juvenile and adult mice. Anti-bombesin serum specifically recognizes Grp but not Nmb. Grp is present in a small number of small-diameter DRG neurons and in abundance in layers I and II of the spinal cord. The reduction of dSC Grp after dorsal root rhizotomy is significantly different from those of DRG derived markers but similar to that of a spinal cord neuronal marker. Double fluorescent in situ of Nmb and other molecular markers indicate that Nmb is highly and selectively expressed in nociceptive and itch-sensitive DRG neurons. Conclusion: The majority of dSC Grp is synthesized locally in dorsal spinal cord neurons. On the other hand, Nmb is highly expressed in pain- and itch-sensing DRG neurons. Our findings provide direct anatomic evidence that Grp could function locally in the dorsal spinal cord in addition to its roles in DRG neurons and that Nmb has potential roles in nociceptive and itch-sensitive neurons. These results will improve our understanding about roles of Grp and Nmb in mediating itch sensation.
Gender differences in mathematics anxiety and the relation to mathematics performance while controlling for test anxiety
Authors: Devine Amy , Fawcett Kayleigh , Szűcs Dénes , Dowker Ann 
Published: July 2012

AbstractBackgroundMathematics anxiety (MA), a state of discomfort associated with performing mathematical tasks, is thought to affect a notable proportion of the school age population. Some research has indicated that MA negatively affects mathematics performance and that girls may report higher levels of MA than boys. On the other hand some research has indicated that boys’ mathematics performance is more negatively affected by MA than girls’ performance is. The aim of the current study was to measure girls’ and boys’ mathematics performance as well as their levels of MA while controlling for test anxiety (TA) a construct related to MA but which is typically not controlled for in MA studies.MethodsFour-hundred and thirty three British secondary school children in school years 7, 8 and 10 completed customised mental mathematics tests and MA and TA questionnaires.ResultsNo gender differences emerged for mathematics performance but levels of MA and TA were higher for girls than for boys. Girls and boys showed a positive correlation between MA and TA and a negative correlation between MA and mathematics performance. TA was also negatively correlated with mathematics performance, but this relationship was stronger for girls than for boys. When controlling for TA, the negative correlation between MA and performance remained for girls only. Regression analyses revealed that MA was a significant predictor of performance for girls but not for boys.ConclusionsOur study has revealed that secondary school children experience MA. Importantly, we controlled for TA which is typically not controlled for in MA studies. Girls showed higher levels of MA than boys and high levels of MA were related to poorer levels of mathematics performance. As well as potentially having a detrimental effect on ‘online’ mathematics performance, past research has shown that high levels of MA can have negative consequences for later mathematics education. Therefore MA warrants attention in the mathematics classroom, particularly because there is evidence that MA develops during the primary school years. Furthermore, our study showed no gender difference in mathematics performance, despite girls reporting higher levels of MA. These results might suggest that girls may have had the potential to perform better than boys in mathematics however their performance may have been attenuated by their higher levels of MA. Longitudinal research is needed to investigate the development of MA and its effect on mathematics performance.
Assessment of the structural and functional impact of in-frame mutations of the DMD gene, using the tools included in the eDystrophin online database
Authors: Nicolas Aurélie , Lucchetti-Miganeh Céline , Yaou Rabah Ben , Kaplan Jean-Claude , Chelly Jamel , Leturcq France , Barloy-Hubler Frédérique , Le Rumeur Elisabeth 
Published: July 2012

Abstract

Background
Dystrophin is a large essential protein of skeletal and heart muscle. It is a filamentous scaffolding protein with numerous binding domains. Mutations in the DMD gene, which encodes dystrophin, mostly result in the deletion of one or several exons and cause Duchenne (DMD) and Becker (BMD) muscular dystrophies. The most common DMD mutations are frameshift mutations resulting in an absence of dystrophin from tissues. In-frame DMD mutations are less frequent and result in a protein with partial wild-type dystrophin function. The aim of this study was to highlight structural and functional modifications of dystrophin caused by in-frame mutations.

Methods and results
We developed a dedicated database for dystrophin, the eDystrophin database. It contains 209 different non frame-shifting mutations found in 945 patients from a French cohort and previous studies. Bioinformatics tools provide models of the three-dimensional structure of the protein at deletion sites, making it possible to determine whether the mutated protein retains the typical filamentous structure of dystrophin. An analysis of the structure of mutated dystrophin molecules showed that hybrid repeats were reconstituted at the deletion site in some cases. These hybrid repeats harbored the typical triple coiled-coil structure of native repeats, which may be correlated with better function in muscle cells.

Conclusion
This new database focuses on the dystrophin protein and its modification due to in-frame deletions in BMD patients. The observation of hybrid repeat reconstitution in some cases provides insight into phenotype-genotype correlations in dystrophin diseases and possible strategies for gene therapy. The eDystrophin database is freely available: http://edystrophin.genouest.org/.
Vector capacity of Anopheles sinensis in malaria outbreak areas of central China
Authors: Pan Jia-Yun , Zhou Shui-Sen , Zheng Xiang , Huang Fang , Wang Duo-Quan , Shen Yu-Zu , Su Yun-Pu , Zhou Guang-Chao , Liu Feng , Jiang Jing-Jing 
Published: July 2012

Abstract

Background
Both falciparum and vivax malaria were historically prevalent in China with high incidence. With the control efforts, the annual incidence in the whole country has reduced to 0.0001% except in some areas in the southern borders after 2000. Despite this, the re-emergence or outbreak of malaria was unavoidable in central China during 2005–2007. In order to understand the role of the vector in the transmission of malaria during the outbreak period, the vector capacity of An. sinensis in Huanghuai valley of central China was investigated.

Findings
The study was undertaken in two sites, namely Huaiyuan county of Anhui province and Yongcheng county of Henan province. In each county, malaria cases were recorded for recent years, and transmission risk factors for each study village including anti-mosquito facilities and total number of livestock were recorded by visiting each household in the study sites. The specimens of mosquitoes were collected in two villages, and population density and species in each study site were recorded after the identification of different species, and the blood-fed mosquitoes were tested by ring precipitation test. Finally, various indicators were calculated to estimate vector capacity or dynamics, including mosquito biting rate (MBR), human blood index (HBI), and the parous rates (M). Finally, the vector capacity, as an important indicator of malaria transmission to predict the potential recurrence of malaria, was estimated and compared in each study site.
About 93.0% of 80 households in Huaiyuan and 89.3% of 192 households in Yongcheng had anti-mosquito facilities. No cattle or pigs were found, only less than 10 sheep were found in each study village. A total of 94 and 107 Anopheles spp. mosquitos were captured in two study sites, respectively, and all of An. sinensis were morphologically identified. It was found that mosquito blood-feeding peak was between 9:00 pm and 12:00 pm. Man biting rate of An. sinensis was 6.0957 and 5.8621 (mosquitoes/people/night) estimated by using half-night human bait trap method and full-capture method, respectively. Human blood indexes (HBI) were 0.6667 (6/9) and 0.6429 (18/28), and man-biting habits were 0.2667 and 0.2572 in two sites, respectively. Therefore, the expectation of infective life and vector capacity of An. sinensis was 0.3649-0.4761 and 0.5502-0.7740, respectively, in Huanhuai valley of central China where the outbreak occurred, which is much higher than that in the previous years without malaria outbreak.

Conclusions
This study suggests that vivax malaria outbreak in Huanhuai valley is highly related to the enhancement in vector capacity of An. sinensis for P. vivax, which is attributed to the local residents’ habits and the remarkable drop in the number of large livestock leading to disappearance of traditional biological barriers.
Utilization of vinasse for production of poly-3-(hydroxybutyrate-co-hydroxyvalerate) by Haloferax mediterranei
Authors: Bhattacharyya Anirban , Pramanik Arnab , Maji Sudipta Kumar , Haldar Saubhik , Mukhopadhyay Ujjal Kumar , Mukherjee Joydeep 
Published: July 2012

Abstract
Vinasse, a highly polluting waste of the ethanol industry was utilized for the production of polyhydroxyalkanoate (PHA) by the extremely halophilic archaeon, Haloferax mediterranei in shake-flasks. Following pre-treatment through adsorption on activated carbon, 25%-50% (v/v) pre-treated vinasse was utilized leading to 70% maximum accumulation of PHA. Maximum PHA concentration of 19.7 g/l, product yield coefficient (based on total carbohydrates) of 0.87 and 0.21 g/l h volumetric productivity were achieved. Concomitant lowering of BOD5 of pre-treated vinasse by at least 78% and COD by at least 80% was attained at the end of this process. The PHA was recovered by osmotic lysis of the cells and purification by sodium hypochlorite and organic solvents. Through UV–vis spectroscopy, gas chromatography, differential scanning calorimetry and nuclear magnetic resonance spectroscopy, the PHA was identified as poly-3-(hydroxybutyrate-co-hydroxyvalerate). The 3-hydroxyvalerate content was 12.36 mol % (utilizing 25% pre-treated vinasse) and 14.09 mol % (utilizing 50% pre-treated vinasse). High salt concentration in the medium allowed this process without sterile conditions and thus reduction in costs of sterilization can be envisaged. Activated charcoal pre-treatment of vinasse is economical than competing processes such as ultrafiltration of whey, extrusion and enzymatic treatment of rice and corn starch. Without impacting sugar prices, this process can easily be integrated into a distillery that has fermentation equipment and trained personnel. High PHA content, productivity, zero-cost carbon source, low-cost isolation of a high-purity product and potential integration into ethanol manufacturing unit with concomitant wastewater treatment should merit further development of this process to higher scales.
Clonal relatedness between lobular carcinoma in situ and synchronous malignant lesions
Authors: Andrade Victor P , Ostrovnaya Irina , Seshan Venkatraman E , Morrogh Mary , Giri Dilip , Olvera Narciso , De Brot Marina , Morrow Monica , Begg Colin B , King Tari A 
Published: July 2012

Abstract
Introduction
Lobular carcinoma in situ (LCIS) has been accepted as a marker of risk for the development of invasive breast cancer, yet modern models of breast carcinogenesis include LCIS as a precursor of low-grade carcinomas. We provide evidence favoring a clonal origin for LCIS and synchronous estrogen receptor-positive malignant lesions of the ductal and lobular phenotype.

Methods
Patients with prior LCIS undergoing mastectomy were identified preoperatively from 2003 to 2008. Specimens were widely sampled, and frozen blocks were screened for LCIS and co-existing malignant lesions, and were subject to microdissection. Samples from 65 patients were hybridized to the Affymetrix SNP 6.0 array platform. Cases with both an LCIS sample and an associated ductal carcinoma in situ (DCIS) or invasive tumor sample were evaluated for patterns of somatic copy number changes to assess evidence of clonal relatedness.

Results
LCIS was identified in 44 of the cases, and among these a DCIS and/or invasive lesion was also identified in 21 cases. A total of 17 tumor pairs had adequate DNA/array data for analysis, including nine pairs of LCIS/invasive lobular cancer, four pairs of LCIS/DCIS, and four pairs of LCIS/invasive ductal cancer. Overall, seven pairs (41%) were judged to be clonally related; in five (29%) evidence suggested clonality but was equivocal, and five (29%) were considered independent. Clonal pairs were observed with all matched lesion types and low and high histological grades. We also show anecdotal evidence of clonality between a patient-matched triplet of LCIS, DCIS, and invasive ductal cancer.

Conclusion
Our results support the role of LCIS as a precursor in the development of both high-grade and low-grade ductal and lobular cancers.
Inter-rater reliability of the Full Outline of UnResponsiveness score and the Glasgow Coma Scale in critically ill patients: a prospective observational study
Authors: Fischer Michael , Rüegg Stephan , Czaplinski Adam , Strohmeier Monika , Lehmann Angelika , Tschan Franziska , Hunziker Patrick R , Marsch Stephan C 
Published: July 2012

Abstract
Introduction
The Glasgow Coma Scale (GCS) is the most widely used scoring system for comatose patients in intensive care. Limitations of the GCS include the impossibility to assess the verbal score in intubated or aphasic patients, and an inconsistent inter-rater reliability. The FOUR (Full Outline of UnResponsiveness) score, a new coma scale not reliant on verbal response, was recently proposed. The aim of the present study was to compare the inter-rater reliability of the GCS and the FOUR score among unselected patients in general critical care. A further aim was to compare the inter-rater reliability of neurologists with that of intensive care unit (ICU) staff.

Methods
In this prospective observational study, scoring of GCS and FOUR score was performed by neurologists and ICU staff on 267 consecutive patients admitted to intensive care.

Results
In a total of 437 pair wise ratings the exact inter-rater agreement for the GCS was 71%, and for the FOUR score 82% (P = 0.0016); the inter-rater agreement within a range of ± 1 score point for the GCS was 90%, and for the FOUR score 92% (P = ns.). The exact inter-rater agreement among neurologists was superior to that among ICU staff for the FOUR score (87% vs. 79%, P = 0.04) but not for the GCS (73% vs. 73%). Neurologists and ICU staff did not significantly differ in the inter-rater agreement within a range of ± 1 score point for both GCS (88% vs. 93%) and the FOUR score (91% vs. 88%).

Conclusions
The FOUR score performed better than the GCS for exact inter-rater agreement, but not for the clinically more relevant agreement within the range of ± 1 score point. Though neurologists outperformed ICU staff with regard to exact inter-rater agreement, the inter-rater agreement of ICU staff within the clinically more relevant range of ± 1 score point equalled that of the neurologists. The small advantage in inter-rater reliability of the FOUR score is most likely insufficient to replace the GCS, a score with a long tradition in intensive care.
Delirium epidemiology in critical care (DECCA): an international study
Authors: Salluh Jorge I , Soares Márcio , Teles José M , Ceraso Daniel , Raimondi Nestor , Nava Victor S , Blasquez Patrícia , Ugarte Sebastian , Ibanez-Guzman Carlos , Centeno José V , Laca Manuel , Grecco Gustavo , Jimenez Edgar , Árias-Rivera Susana , Duenas Carmelo , Rocha Marcelo G 
Published: July 2012

Abstract
Introduction
Delirium is a frequent source of morbidity in intensive care units (ICUs). Most data on its epidemiology is from single-center studies. Our aim was to conduct a multicenter study to evaluate the epidemiology of delirium in the ICU.

Methods
A 1-day point-prevalence study was undertaken in 104 ICUs from 11 countries in South and North America and Spain.

Results
In total, 975 patients were screened, and 497 fulfilled inclusion criteria and were enrolled (median age, 62 years; 52.5% men; 16.7% and 19.9% for ICU and hospital mortality); 64% were admitted to the ICU because of medical causes, and sepsis was the main diagnosis (n = 76; 15.3%). In total, 265 patients were sedated with the Richmond agitation and sedation scale (RASS) deeper than -3, and only 232 (46.6%) patients could be evaluated with the confusion-assessment method for the ICU. The prevalence of delirium was 32.3%. Compared with patients without delirium, those with the diagnosis of delirium had a greater severity of illness at admission, demonstrated by higher sequential organ-failure assessment (SOFA (P = 0.004)) and simplified acute physiology score 3 (SAPS3) scores (P < 0.0001). Delirium was associated with increased ICU (20% versus 5.7%; P = 0.002) and hospital mortality (24 versus 8.3%; P = 0.0017), and longer ICU (P < 0.0001) and hospital length of stay (LOS) (22 (11 to 40) versus 7 (4 to 18) days; P < 0.0001). Previous use of midazolam (P = 0.009) was more frequent in patients with delirium. On multivariate analysis, delirium was independently associated with increased ICU mortality (OR = 3.14 (1.26 to 7.86); CI, 95%) and hospital mortality (OR = 2.5 (1.1 to 5.7); CI, 95%).

Conclusions
In this 1-day international study, delirium was frequent and associated with increased mortality and ICU LOS. The main modifiable risk factors associated with the diagnosis of delirium were the use of invasive devices and sedatives (midazolam).