bluuebunny/crossref_metadata_2025 huggingface dataset:
A 2-step approach to myeloablative haploidentical stem cell transplantation: a phase 1/2 trial performed with optimized T-cell dosing
Authors: Grosso Dolores , Carabasi Matthew , Filicko-O'Hara Joanne , Kasner Margaret , Wagner John L. , Colombe Beth , Cornett Farley Patricia , O'Hara William , Flomenberg Phyllis , Werner-Wasik Maria , Brunner Janet , Mookerjee Bijoyesh , Hyslop Terry , Weiss Mark , Flomenberg Neal
Published: August 2011

Studies of haploidentical hematopoietic stem cell transplantation (HSCT) have identified threshold doses of T cells below which severe GVHD is usually absent. However, little is known regarding optimal T-cell dosing as it relates to engraftment, immune reconstitution, and relapse. To begin to address this question, we developed a 2-step myeloablative approach to haploidentical HSCT in which 27 patients conditioned with total body irradiation (TBI) were given a fixed dose of donor T cells (HSCT step 1), followed by cyclophosphamide (CY) for T-cell tolerization. A CD34-selected HSC product (HSCT step 2) was infused after CY. A dose of 2 × 108/kg of T cells resulted in consistent engraftment, immune reconstitution, and acceptable rates of GVHD. Cumulative incidences of grade III-IV GVHD, nonrelapse mortality (NRM), and relapse-related mortality were 7.4%, 22.2%, and 29.6%, respectively. With a follow-up of 28-56 months, the 3-year probability of overall survival for the whole cohort is 48% and 75% in patients without disease at HSCT. In the context of CY tolerization, a high, fixed dose of haploidentical T cells was associated with encouraging outcomes, especially in good-risk patients, and can serve as the basis for further exploration and optimization of this 2-step approach. This study is registered at www.clinicaltrials.gov as NCT00429143.
Funding mechanisms and program management at the National Heart, Lung, and Blood Institute: confronting new challenges and exploring new opportunities
Authors: Shurin Susan B.
Published: August 2011

Over the past 8 years, the National Institutes of Health (NIH) budget appropriation has lost purchasing power, with erosion of the benefits of the doubling of the budget less than a decade ago. For the first time in 40 years, the NIH appropriation in fiscal year 2011 was 1% less than in the previous year. The National Heart, Lung, and Blood Institute (NHLBI) has been closely managing its funds to protect its core functions: support and conduct of research, and training of biomedical research scientists. Rigorous evaluations of funding mechanisms, management of clinical studies, set-aside programs and funding guidelines are designed to help the Institute, in consultation with its advisory council, to minimize the long-term impact of extreme resource limitations on the advance and conduct of science. This report describes some recent actions taken by the NHLBI to maximize support for investigator-initiated research, maintain a balanced portfolio, and provide as much support as possible for established and early-stage investigators.
Gene- or region-based association study via kernel principal component analysis
Authors: Gao Qingsong , He Yungang , Yuan Zhongshang , Zhao Jinghua , Zhang Bingbing , Xue Fuzhong
Published: August 2011

Background

In genetic association study, especially in GWAS, gene- or region-based methods have been more popular to detect the association between multiple SNPs and diseases (or traits). Kernel principal component analysis combined with logistic regression test (KPCA-LRT) has been successfully used in classifying gene expression data. Nevertheless, the purpose of association study is to detect the correlation between genetic variations and disease rather than to classify the sample, and the genomic data is categorical rather than numerical. Recently, although the kernel-based logistic regression model in association study has been proposed by projecting the nonlinear original SNPs data into a linear feature space, it is still impacted by multicolinearity between the projections, which may lead to loss of power. We, therefore, proposed a KPCA-LRT model to avoid the multicolinearity.

Results

Simulation results showed that KPCA-LRT was always more powerful than principal component analysis combined with logistic regression test (PCA-LRT) at different sample sizes, different significant levels and different relative risks, especially at the genewide level (1E-5) and lower relative risks (RR = 1.2, 1.3). Application to the four gene regions of rheumatoid arthritis (RA) data from Genetic Analysis Workshop16 (GAW16) indicated that KPCA-LRT had better performance than single-locus test and PCA-LRT.

Conclusions

KPCA-LRT is a valid and powerful gene- or region-based method for the analysis of GWAS data set, especially under lower relative risks and lower significant levels.
Evaluation of two commercial global miRNA expression profiling platforms for detection of less abundant miRNAs
Authors: Jensen Steffen G , Lamy Philippe , Rasmussen Mads H , Ostenfeld Marie S , Dyrskjøt Lars , Ørntoft Torben F , Andersen Claus L
Published: August 2011

Background

microRNAs (miRNA) are short, endogenous transcripts that negatively regulate the expression of specific mRNA targets. miRNAs are found both in tissues and body fluids such as plasma. A major perspective for the use of miRNAs in the clinical setting is as diagnostic plasma markers for neoplasia. While miRNAs are abundant in tissues, they are often scarce in plasma. For quantification of miRNA in plasma it is therefore of importance to use a platform with high sensitivity and linear performance in the low concentration range. This motivated us to evaluate the performance of three commonly used commercial miRNA quantification platforms: GeneChip miRNA 2.0 Array, miRCURY Ready-to-Use PCR, Human panel I+II V1.M, and TaqMan Human MicroRNA Array v3.0.

Results

Using synthetic miRNA samples and plasma RNA samples spiked with different ratios of 174 synthetic miRNAs we assessed the performance characteristics reproducibility, recovery, specificity, sensitivity and linearity. It was found that while the qRT-PCR based platforms were sufficiently sensitive to reproducibly detect miRNAs at the abundance levels found in human plasma, the array based platform was not. At high miRNA levels both qRT-PCR based platforms performed well in terms of specificity, reproducibility and recovery. At low miRNA levels, as in plasma, the miRCURY platform showed better sensitivity and linearity than the TaqMan platform.

Conclusion

For profiling clinical samples with low miRNA abundance, such as plasma samples, the miRCURY platform with its better sensitivity and linearity would probably be superior.
Evaluation of stool microbiota signatures in two cohorts of Asian (Singapore and Indonesia) newborns at risk of atopy
Authors: Yap Gaik Chin , Chee Kok Keong , Hong Pei-Ying , Lay Christophe , Satria Cahya D , Sumadiono  , Soenarto Yati , Haksari Ekawaty L , Aw Marion , Shek Lynette Pei-Chi , Chua Kaw Yan , Zhao Yudong , Leow Doreen , Lee Bee Wah
Published: August 2011

Background

Studies have suggested that demographic and lifestyle factors could shape the composition of fecal microbiota in early life. This study evaluated infant stool microbiota signatures in two Asian populations, Singapore (n = 42) and Indonesia (n = 32) with contrasting socioeconomic development, and examined the putative influences of demographic factors on these human fecal associated bacterial signatures.

Results

Longitudinal analysis showed associations of geographical origin withClostridium leptum, AtopobiumandBifidobacteriumgroups. Mode of delivery had the largest effect on stool microbiota signatures influencing the abundance of four bacterial groups. Significantly higher abundance of bacterial members belonging to theBacteroides-Prevotella, BifidobacteriumandAtopobiumgroups, but lower abundance ofLactobacilli-Enterococcigroup members, were observed in vaginal delivered compared to caesarean delivered infants. Demographic factors influencing the structure of infants stool microbiota during the first year of life included breastfeeding, age of weaning, sibship size and exposure to antibiotics.

Conclusions

Differences in stool microbiota signatures were observed in relation to various demographic factors. These features may confound studies relating to the association of the structure of fecal microbiota and the predisposition to human modern disease.
An analysis of national target groups for monovalent 2009 pandemic influenza vaccine and trivalent seasonal influenza vaccines in 2009-10 and 2010-11
Authors: Ng Sophia , Wu Peng , Nishiura Hiroshi , Ip Dennis KM , Lee Esther ST , Cowling Benjamin J
Published: August 2011

Background

Vaccination is generally considered to be the best primary prevention measure against influenza virus infection. Many countries encourage specific target groups of people to undertake vaccination, often with financial subsidies or a priority list. To understand differential patterns of national target groups for influenza vaccination before, during and after the 2009 influenza pandemic, we reviewed and analyzed the country-specific policies in the corresponding time periods.

Methods

Information on prioritized groups targeted to receive seasonal and pandemic influenza vaccines was derived from a multi-step internet search of official health department websites, press releases, media sources and academic journal articles. We assessed the frequency and consistency of targeting 20 different groups within populations which are associated with age, underlying medical conditions, role or occupations among different countries and vaccines. Information on subsidies provided to specific target groups was also extracted.

Results

We analyzed target groups for 33 (seasonal 2009 and 2009-10 vaccines), 72 (monovalent pandemic 2009-10 vaccine) and 34 (seasonal 2010 and 2010-11 vaccines) countries. In 2009-10, the elderly, those with chronic illness and health care workers were common targets for the seasonal vaccine. Comparatively, the elderly, care home residents and workers, animal contacts and close contacts were less frequently targeted to receive the pandemic vaccine. Pregnant women, obese persons, essential community workers and health care workers, however, were more commonly targeted. After the pandemic, pregnant women, obese persons, health care and care home workers, and close contacts were more commonly targeted to receive the seasonal vaccine compared to 2009-10, showing continued influence from the pandemic. Many of the countries provided free vaccines, partial subsidies, reimbursements or national health insurance coverage to specific target groups and over one-third of the countries offered universal subsidy regarding the pandemic vaccine. There was also some inconsistency between countries in target groups.

Conclusions

Differences in target groups between countries may reflect variable objectives as well as uncertainties regarding the transmission dynamics, severity and age-specific immunity against influenza viruses before and after vaccination. Clarification on these points is essential to elucidate optimal and object-oriented vaccination strategies.
P53 suppresses expression of the 14-3-3gamma oncogene
Authors: Radhakrishnan Vijayababu M , Putnam Charles W , Qi Wenqing , Martinez Jesse D
Published: August 2011

Background

14-3-3 proteins are a family of highly conserved proteins that are involved in a wide range of cellular processes. Recent evidence indicates that some of these proteins have oncogenic activity and that they may promote tumorigenesis. We previously showed that one of the 14-3-3 family members, 14-3-3gamma, is over expressed in human lung cancers and that it can induce transformation of rodent cells in vitro.

Methods

qRTPCR and Western blot analysis were performed to examine 14-3-3gamma expression in non-small cell lung cancers (NSCLC). Gene copy number was analyzed by qPCR. P53 mutations were detected by direct sequencing and also by western blot. CHIP and yeast one hybrid assays were used to detect p53 binding to 14-3-3gamma promoter.

Results

Quantitative rtPCR results showed that the expression level of 14-3-3gamma was elevated in the majority of NSCLC that we examined which was also consistent with protein expression. Further analysis of the expression pattern of 14-3-3gamma in lung tumors showed a correlation with p53 mutations suggesting that p53 might suppress 14-3-3 gamma expression. Analysis of the gamma promoter sequence revealed the presence of a p53 consensus binding motif and in vitro assays demonstrated that wild-type p53 bound to this motif when activated by ionizing radiation. Deletion of the p53 binding motif eliminated p53's ability to suppress 14-3-3gamma expression.

Conclusion

Increased expression of 14-3-3gamma in lung cancer coincides with loss of functional p53. Hence, we propose that 14-3-3gamma's oncogenic activities cooperate with loss of p53 to promote lung tumorigenesis.
EFS shows biallelic methylation in uveal melanoma with poor prognosis as well as tissue-specific methylation
Authors: Neumann Lisa C , Weinhäusel Andreas , Thomas Stefanie , Horsthemke Bernhard , Lohmann Dietmar R , Zeschnigk Michael
Published: August 2011

Background

Uveal melanoma (UM) is a rare eye tumor. There are two classes of UM, which can be discriminated by the chromosome 3 status or global mRNA expression profile. Metastatic progression is predominantly originated from class II tumors or from tumors showing loss of an entire chromosome 3 (monosomy 3). We performed detailed EFS (embryonal Fyn-associated substrate) methylation analyses in UM, cultured uveal melanocytes and normal tissues, to explore the role of the differentially methylated EFS promoter region CpG island in tumor classification and metastatic progression.

Methods

EFS methylation was determined by direct sequencing of PCR products from bisulfite-treated DNA or by sequence analysis of individual cloned PCR products. The results were associated with clinical features of tumors and tumor-related death of patients.

Results

Analysis of 16 UM showed full methylation of the EFS CpG island in 8 (50%), no methylation in 5 (31%) and partial methylation in 3 (19%) tumors. Kaplan-Meier analysis revealed a higher risk of metastatic progression for tumors with EFS methylation (p = 0.02). This correlation was confirmed in an independent set of 24 randomly chosen tumors. Notably, only UM with EFS methylation gave rise to metastases. Real-time quantitative RT-PCR expression analysis revealed a significant inverse correlation of EFS mRNA expression with EFS methylation in UM. We further found that EFS methylation is tissue-specific with full methylation in peripheral blood cells, and no methylation in sperm, cultured primary fibroblasts and fetal muscle, kidney and brain. Adult brain samples, cultured melanocytes from the uveal tract, fetal liver and 3 of 4 buccal swab samples showed partial methylation. EFS methylation always affects both alleles in normal and tumor samples.

Conclusions

Biallelic EFS methylation is likely to be the result of a site-directed methylation mechanism. Based on partial methylation as observed in cultured melanocytes we hypothesize that there might be methylated and unmethylated precursor cells located in the uveal tract. The EFS methylation of a UM may depend on which type of precursor cell the tumor originated from.
Automatic segmentation of meningioma from non-contrasted brain MRI integrating fuzzy clustering and region growing
Authors: Hsieh Thomas M , Liu Yi-Min , Liao Chun-Chih , Xiao Furen , Chiang I-Jen , Wong Jau-Min
Published: August 2011

Background

In recent years, magnetic resonance imaging (MRI) has become important in brain tumor diagnosis. Using this modality, physicians can locate specific pathologies by analyzing differences in tissue character presented in different types of MR images.

This paper uses an algorithm integrating fuzzy-c-mean (FCM) and region growing techniques for automated tumor image segmentation from patients with menigioma. Only non-contrasted T1 and T2 -weighted MR images are included in the analysis. The study's aims are to correctly locate tumors in the images, and to detect those situated in the midline position of the brain.

Methods

The study used non-contrasted T1- and T2-weighted MR images from 29 patients with menigioma. After FCM clustering, 32 groups of images from each patient group were put through the region-growing procedure for pixels aggregation. Later, using knowledge-based information, the system selected tumor-containing images from these groups and merged them into one tumor image. An alternative semi-supervised method was added at this stage for comparison with the automatic method. Finally, the tumor image was optimized by a morphology operator. Results from automatic segmentation were compared to the "ground truth" (GT) on a pixel level. Overall data were then evaluated using a quantified system.

Results

The quantified parameters, including the "percent match" (PM) and "correlation ratio" (CR), suggested a high match between GT and the present study's system, as well as a fair level of correspondence. The results were compatible with those from other related studies. The system successfully detected all of the tumors situated at the midline of brain.

Six cases failed in the automatic group. One also failed in the semi-supervised alternative. The remaining five cases presented noticeable edema inside the brain. In the 23 successful cases, the PM and CR values in the two groups were highly related.

Conclusions

Results indicated that, even when using only two sets of non-contrasted MR images, the system is a reliable and efficient method of brain-tumor detection. With further development the system demonstrates high potential for practical clinical use.
Strategies to improve palatability and increase consumption intentions for Momordica charantia(bitter melon): A vegetable commonly used for diabetes management
Authors: Snee Laura S , Nerurkar Vivek R , Dooley Dian A , Efird Jimmy T , Shovic Anne C , Nerurkar Pratibha V
Published: August 2011

Background

Although beneficial to health, dietary phytonutrients are bitter, acid and/or astringent in taste and therefore reduce consumer choice and acceptance during food selection. Momordica charantia, commonly known as bitter melon has been traditionally used in Ayurvedic and Chinese medicine to treat diabetes and its complications. The aim of this study was to develop bitter melon-containing recipes and test their palatability and acceptability in healthy individuals for future clinical studies.

Methods

A cross-sectional sensory evaluation of bitter melon-containing ethnic recipes was conducted among 50 healthy individuals. The primary endpoints assessed in this analysis were current consumption information and future intentions to consume bitter melon, before and after provision of attribute- and health-specific information. A convenience sample of 50, self-reported non-diabetic adults were recruited from the University of Hawaii. Sensory evaluations were compared using two-way ANOVA, while differences in stage of change (SOC) before and after receiving health information were analyzed by Chi-square (χ2) analyses.

Results

Our studies indicate that tomato-based recipes were acceptable to most of the participants and readily acceptable, as compared with recipes containing spices such as curry powder. Health information did not have a significant effect on willingness to consume bitter melon, but positively affected the classification of SOC.

Conclusions

This study suggests that incorporating bitter foods in commonly consumed food dishes can mask bitter taste of bitter melon. Furthermore, providing positive health information can elicit a change in the intent to consume bitter melon-containing dishes despite mixed palatability results.
Isolated angiitis of the central nervous system with tumor-like lesion, mimicking brain malignant glioma: a case report and review of the literature
Authors: You Gan , Yan Wei , Zhang Wei , Li Shaowu , Li Guilin , Jiang Tao
Published: August 2011

Background

Isolated angiitis of the central nervous system (IACNS) is a rare but severe vascular disease, which could present like an isolated inflammatory lesion on magnetic resonance imaging (MRI). To date, only a few such cases with tumor-like IACNS have been reported.

Case Presentation

A 35-year-old woman presented with headache and left-sided weakness. MRI scans initially mislead us to a diagnosis of glioblastoma (GBM). Surgery was performed. The mass was sub-totally resected. Pathological examination confirmed a cerebral vasculitis. Radiological features, such as disproportionate mass effect, striped hemorrhage and abnormal enhancement of adjacent vessels, could be helpful to distinguish a tumor-like IACNS from a GBM. Single therapy with high doses of steroid did not improve the patient's condition. Combined therapy with prednisolone and cyclophosphamide showed great benefit to the patient. No relapse occurred during the period of 18 months follow-up.

Conclusions

Although a tumor-like IACNS has no established imaging features, a diagnosis of tumor-like IACNS should be suspected when MRI shows inappropriate presentations of a tumor. Greater awareness of this potential manifestation of IACNS may facilitate more prompt diagnosis and treatment.
Acute heart failure caused by a giant hepatocellular metastatic tumor of the right atrium
Authors: Dedeilias Panagiotis , Nenekidis Ioannis , Koukis Ioannis , Anagnostakou Vania , Paparizou Niki , Zompolos Spyros , Apostolakis Efstratios
Published: August 2011

We present a symptomatic 40-year-old cirrhotic man who presented with sudden onsets of syncope. Echocardiography revealed right ventricular outflow track obstruction caused by a huge right atrial mass. The tumor was surgically excised under cardiopulmonary bypass. Although no primary cancerous lesion in the liver was detected, histopathology revealed that the mass was a metastatic hepatocellular carcinoma. The aim of this report is to show the value of urgent preoperative computed tomography and its contribution in the operative strategy. The importance of urgent surgical treatment with tricuspid valve sparing tumor resection is emphasized even though the prognosis for such patients is dismal. We also discuss the further management options of such rare cases
Evaluation of the global association between cholesterol-associated polymorphisms and Alzheimer's disease suggests a role for rs3846662 and HMGCR splicing in disease risk
Authors: Simmons Christopher R , Zou Fanggeng , Younkin Steven G , Estus Steven
Published: August 2011

Background

Recent genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNP)s that are essentially unequivocally associated with peripheral cholesterol. Since the alleles of the APOE gene, which modulate peripheral cholesterol metabolism, and midlife plasma cholesterol are both associated with Alzheimer's disease (AD) risk, we have evaluated the hypothesis that SNPs associated with plasma cholesterol are also associated with AD.

Results

Seventeen non-APOE SNPs reproducibly associated with cholesterol per GWAS were tested for association with AD in ~2,000 AD and ~4,000 non-AD subjects. As a group, these SNPs are associated with AD. Two SNPs in particular, rs3846662 and rs1532085, are associated with AD risk and age-of-onset. Additionally, rs3846662 was associated with HMGCR exon 13 splicing in human liver but not brain, possibly obscured by CNS cell-type heterogeneity. However, rs3846662 was associated with HMGCR exon 13 splicing in liver- and brain-derived cell lines.

Conclusions

Cholesterol-associated SNPs outside of APOE confer a global risk for AD. Rs3846662 and rs1532085 are associated with both AD risk and age-of-onset. Rs3846662 is associated with HMGCR exon 13 inclusion. Since rs3846662 affects AD risk and age-of-onset as well as statin responsiveness, this SNP may confound clinical trials evaluating the protective effects of statins on AD.
Congenital aplasia of the optic chiasm and esophageal atresia: a case report
Authors: Pensiero Stefano , Cecchini Paolo , Michieletto Paola , Pelizzo Gloria , Madonia Maurizio , Parentin Fulvio
Published: August 2011

Introduction

The complete absence of the chiasm (chiasmal aplasia) is a rare clinical condition. Hypoplasia of the optic nerve and congenital nystagmus are almost invariably associated characteristics. Microphthalmos or anophthalmos are common features in chiasmal aplasia, while central nervous system abnormalities are less frequent. Esophageal atresia can be isolated or syndromic. In syndromic cases, it is frequently associated with cardiac, limb, renal or vertebral malformations and anal atresia. More rarely, esophageal atresia can be part of anophthalmia-esophageal-genital syndrome, which comprises anophthalmia or microphthalmia, genital abnormalities, vertebral defects and cerebral malformations. Here, a previously unreported case of chiasmal aplasia presenting without microphthalmos and associated with esophageal atresia is described.

Case presentation

Aplasia of the optic chiasm was identified in a Caucasian Italian 8-month-old boy with esophageal atresia. An ultrasound examination carried out at 21 weeks' gestation revealed polyhydramnios. Intrauterine growth retardation, esophageal atresia and a small atrial-septal defect were subsequently detected at 28 weeks' gestation. Repair of the esophageal atresia was carried out shortly after birth. A jejunostomy was carried out at four months to facilitate enteral feeding. The child was subsequently noted to be visually inattentive and to be neurodevelopmentally delayed. Magnetic resonance imaging revealed chiasmal aplasia. No other midline brain defects were found. His karyotype was normal.

Conclusion

If achiasmia is a spectrum, our patient seems to depict the most severe form, since he appears to have an extremely severe visual impairment. This is in contrast to most of the cases described in the literature, where patients maintain good--or at least useful-- visual function. To the best of our knowledge, the association of optic nerve hypoplasia, complete chiasmal aplasia, esophageal atresia and atrial-septal defect, choanal atresia, hypertelorism and psychomotor retardation has never been described before.
Therapeutic options to prevent recurrence of an aggressive aneurysmatic bone cyst of the cervical spine of a 16 year old boy - a case report
Authors: Richter Juliane , Tschöke Sven K , Gulow Jens , Eichfeld Uwe , Wojan Magdalena , von Salis-Soglio Georg , Heyde Christoph E
Published: August 2011

The aneurysmatic bone cyst (ABC) is a benign primary bone tumour. If located in the cervical spine, its expansive growth and destructive behaviour may lead to instability and serious neurological impairment. We report a case of a 16-year-old boy with an aggressive ABC in the 7thcervical vertebra. Computertomographic and magnetic resonance imaging revealed the envelopment of the left 7thand 8thspinal nerve along with the anterior displacement of the left vertebral artery. The interdisciplinary surgical strategy consisted of a partially incomplete cyst resection, subtotal spondylectomy with posterior screw-and-rod fixation from C6-Th1, iliac crest bone grafting and anterior plating from C6-Th1. With regard to the high rate of recurrence after incomplete resection published in the recent literature, the patient was postoperatively treated by megavoltage radiotherapy with a total dose of 30Gy (daily dose of 1.8 Gy for 3 weeks). The clinical and radiographic follow-up showed complete recovery of all neurologic impairments and no signs of tumour recurrence at 3, 6 and 12 months after surgery. This case highlights diverse treatment regimens and shall outline the challenge and the problems of the interdisciplinary decision-making in adolescents presenting with ABC in high-demanding anatomical regions.
Tunisian Toxoplasma gondii strains genotyping by the use of AK69 marker
Authors: Boughattas Sonia , Ben-Abdallah Rym , Siala Emna , Ben-Abda Imen , Souissi Olfa , Aoun Karim , Bouratbine Aida
Published: August 2011

Background

Clinical manifestation due to infection by Toxoplasma gondii is closely linked to the infecting strain of the parasite. Several genetic markers are available to determinate its genotype but few of them are able to discriminate between the three predominant lineages, namely types I, II and III. The number of markers decreases when atypical, recombinant/mixed genotypes need to be identified.

Findings

In our study, the contribution of sequence polymorphisms in the AK69 gene as typing markers for T. gondii was investigated for the first time in an epidemiological study. The coding region of the marker was amplified, sequenced and aligned for different Toxoplasma strains. The identified nucleotide polymorphism at 12 positions was able to highly discriminate between the different congenital toxoplasmosis Tunisian strains. Moreover the high detection sensitivity level of the marker enabled unambiguous identification of mixed/recombinant genotypes directly.

Conclusion

It can be, thus, very useful for direct typing in areas where such genotypes are frequently encountered, mainly in the African continent.
1α,25-Dihydroxyvitamin D3 enhances cerebral clearance of human amyloid-β peptide(1-40) from mouse brain across the blood-brain barrier
Authors: Ito Shingo , Ohtsuki Sumio , Nezu Yasuko , Koitabashi Yusuke , Murata Sho , Terasaki Tetsuya
Published: August 2011

Background

Cerebrovascular dysfunction has been considered to cause impairment of cerebral amyloid-β peptide (Aβ) clearance across the blood-brain barrier (BBB). Further, low levels of vitamin D are associated with increased risk of Alzheimer's disease, as well as vascular dysfunction. The purpose of the present study was to investigate the effect of 1α,25-dihydroxyvitamin D3(1,25(OH)2D3), an active form of vitamin D, on cerebral Aβ clearance from mouse brain.

Methods

The elimination of [125I]hAβ(1-40) from mouse brain was examined by using the Brain Efflux Index method to determine the remaining amount of [125I]hAβ(1-40) radioactivity after injection into the cerebral cortex. [125I]hAβ(1-40) internalization was analyzed using conditionally immortalized mouse brain capillary endothelial cells (TM-BBB4).

Results

Twenty-four hours after intraperitoneal injection of 1,25(OH)2D3 (1 μg/mouse), [125I]hAβ(1-40) elimination from mouse brain was increased 1.3-fold, and the level of endogenous Aβ(1-40) in mouse brain was reduced. These effects were observed at 24 h after i.p. injection of 1,25(OH)2D3, while no significant effect was observed at 48 or 72 h. Vitamin D receptor (VDR) mRNA was detected in mouse brain capillaries, suggesting that 1,25(OH)2D3 has a VDR-mediated genomic action. Furthermore, forskolin, which activates mitogen-activated protein kinase kinase (MEK), enhanced [125I]hAβ(1-40) elimination from mouse brain. Forskolin also enhanced [125I]hAβ(1-40) internalization in TM-BBB4 cells, and this enhancement was inhibited by a MEK inhibitor, suggesting involvement of non-genomic action.

Conclusions

The active form of vitamin D, 1,25(OH)2D3, appears to enhance brain-to-blood Aβ(1-40) efflux transport at the BBB through both genomic and non-genomic actions. Compounds activating these pathways may be candidate agents for modulating Aβ(1-40) elimination at the BBB.
Amyloid-beta transporter expression at the blood-CSF barrier is age-dependent
Authors: Pascale Crissey L , Miller Miles C , Chiu Catherine , Boylan Matthew , Caralopoulos Ilias N , Gonzalez Liliana , Johanson Conrad E , Silverberg Gerald D
Published: August 2011

Background

Age is the major risk factor for many neurodegenerative diseases, including Alzheimer's disease (AD). There is an accumulation of amyloid-beta peptides (Aβ) in both the AD brain and the normal aging brain. Clearance of Aβ from the brain occurs via active transport at the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB). With increasing age, the expression of the Aβ efflux transporters is decreased and the Aβ influx transporter expression is increased at the BBB, adding to the amyloid burden in the brain. Expression of the Aβ transporters at the choroid plexus (CP) epithelium as a function of aging was the subject of this study.

Methods

This project investigated the changes in expression of the Aβ transporters, the low density lipoprotein receptor-related protein-1 (LRP-1), P-glycoprotein (P-gp), LRP-2 (megalin) and the receptor for advanced glycation end-products (RAGE) at the BCSFB in Brown-Norway/Fischer rats at ages 3, 6, 9, 12, 20, 30 and 36 months, using real time RT-PCR to measure transporter mRNA expression, and immunohistochemistry (IHC) to measure transporter protein in isolated rat CP.

Results

There was an increase in the transcription of the Aβ efflux transporters, LRP-1 and P-gp, no change in RAGE expression and a decrease in LRP-2, the CP epithelium influx transporter, at the BCSFB with aging. Decreased Aβ42 concentration in the CP, as measured by quantitative IHC, was associated with these Aβ transporter alterations.

Conclusions

Age-dependent alterations in the CP Aβ transporters are associated with a decrease in Aβ42 accumulation in the CP, and are reciprocal to the changes seen in these transporters at the BBB, suggesting a possible compensatory role for the BCSFB in Aβ clearance in aging.
Kinematic and dynamic gait compensations in a rat model of lumbar radiculopathy and the effects of tumor necrosis factor-alpha antagonism
Authors: Allen Kyle D , Shamji Mohammed F , Mata Brian A , Gabr Mostafa A , Sinclair S Michael , Schmitt Daniel O , Richardson William J , Setton Lori A
Published: August 2011

Introduction

Tumor necrosis factor-α (TNFα) has received significant attention as a mediator of lumbar radiculopathy, with interest in TNF antagonism to treat radiculopathy. Prior studies have demonstrated that TNF antagonists can attenuate heightened nociception resulting from lumbar radiculopathy in the preclinical model. Less is known about the potential impact of TNF antagonism on gait compensations, despite being of clinical relevance. In this study, we expand on previous descriptions of gait compensations resulting from lumbar radiculopathy in the rat and describe the ability of local TNF antagonism to prevent the development of gait compensations, altered weight bearing, and heightened nociception.

Methods

Eighteen male Sprague-Dawley rats were investigated for mechanical sensitivity, weight-bearing, and gait pre- and post-operatively. For surgery, tail nucleus pulposus (NP) tissue was collected and the right L5 dorsal root ganglion (DRG) was exposed (Day 0). In sham animals, NP tissue was discarded (n = 6); for experimental animals, autologous NP was placed on the DRG with or without 20 μg of soluble TNF receptor type II (sTNFRII, n = 6 per group). Spatiotemporal gait characteristics (open arena) and mechanical sensitivity (von Frey filaments) were assessed on post-operative Day 5; gait dynamics (force plate arena) and weight-bearing (incapacitance meter) were assessed on post-operative Day 6.

Results

High-speed gait characterization revealed animals with NP alone had a 5% decrease in stance time on their affected limbs on Day 5 (P ≤0.032). Ground reaction force analysis on Day 6 aligned with temporal changes observed on Day 5, with vertical impulse reduced in the affected limb of animals with NP alone (area under the vertical force-time curve, P <0.02). Concordant with gait, animals with NP alone also had some evidence of affected limb mechanical allodynia on Day 5 (P = 0.08) and reduced weight-bearing on the affected limb on Day 6 (P <0.05). Delivery of sTNFRII at the time of NP placement ameliorated signs of mechanical hypersensitivity, imbalanced weight distribution, and gait compensations (P <0.1).

Conclusions

Our data indicate gait characterization has value for describing early limb dysfunctions in pre-clinical models of lumbar radiculopathy. Furthermore, TNF antagonism prevented the development of gait compensations subsequent to lumbar radiculopathy in our model.
Admissions to intensive care unit of HIV-infected patients in the era of highly active antiretroviral therapy: etiology and prognostic factors
Authors: Chiang Hou-Hsien , Hung Chien-Ching , Lee Chang-Min , Chen Hsuan-Yu , Chen Mao-Yuan , Sheng Wang-Huei , Hsieh Szu-Min , Sun Hsin-Yun , Ho Chao-Chi , Yu Chong-Jen
Published: August 2011

Introduction

Although access to highly active antiretroviral therapy (HAART) has prolonged survival and improved life quality, HIV-infected patients with severe immunosuppression or comorbidities may develop complications that require critical care support in intensive care units (ICU). This study aimed to describe the etiology and analyze the prognostic factors of HIV-infected Taiwanese patients in the HAART era.

Methods

Medical records of all HIV-infected adults who were admitted to ICU at a university hospital in Taiwan from 2001 to 2010 were reviewed to record information on patient demographics, receipt of HAART, and reason for ICU admission. Factors associated with hospital mortality were analyzed.

Results

During the 10-year study period, there were 145 ICU admissions for 135 patients, with respiratory failure being the most common cause (44.4%), followed by sepsis (33.3%) and neurological disease (11.9%). Receipt of HAART was not associated with survival. However, CD4 count was independently predictive of hospital mortality (adjusted odds ratio [AOR], per-10 cells/mm3 decrease, 1.036; 95% confidence interval [CI], 1.003 to 1.069). Admission diagnosis of sepsis was independently associated with hospital mortality (AOR, 2.91; 95% CI, 1.11 to 7.62). A hospital-to-ICU interval of more than 24 hours and serum albumin level (per 1-g/dl decrease) were associated with increased hospital mortality, but did not reach statistical significance in multivariable analysis.

Conclusions

Respiratory failure was the leading cause of ICU admissions among HIV-infected patients in Taiwan. Outcome during the ICU stay was associated with CD4 count and the diagnosis of sepsis, but was not associated with HAART in this study.
Residues within the Transmembrane Domain of the Glucagon-Like Peptide-1 Receptor Involved in Ligand Binding and Receptor Activation: Modelling the Ligand-Bound Receptor
Authors: Coopman K. , Wallis R. , Robb G. , Brown A. J. H. , Wilkinson G. F. , Timms D. , Willars G. B.
Published: August 2011

The C-terminal regions of glucagon-like peptide-1 (GLP-1) bind to the N terminus of the GLP-1 receptor (GLP-1R), facilitating interaction of the ligand N terminus with the receptor transmembrane domain. In contrast, the agonist exendin-4 relies less on the transmembrane domain, and truncated antagonist analogs (e.g. exendin 9–39) may interact solely with the receptor N terminus. Here we used mutagenesis to explore the role of residues highly conserved in the predicted transmembrane helices of mammalian GLP-1Rs and conserved in family B G protein coupled receptors in ligand binding and GLP-1R activation. By iteration using information from the mutagenesis, along with the available crystal structure of the receptor N terminus and a model of the active opsin transmembrane domain, we developed a structural receptor model with GLP-1 bound and used this to better understand consequences of mutations. Mutation at Y152 [transmembrane helix (TM) 1], R190 (TM2), Y235 (TM3), H363 (TM6), and E364 (TM6) produced similar reductions in affinity for GLP-1 and exendin 9–39. In contrast, other mutations either preferentially [K197 (TM2), Q234 (TM3), and W284 (extracellular loop 2)] or solely [D198 (TM2) and R310 (TM5)] reduced GLP-1 affinity. Reduced agonist affinity was always associated with reduced potency. However, reductions in potency exceeded reductions in agonist affinity for K197A, W284A, and R310A, while H363A was uncoupled from cAMP generation, highlighting critical roles of these residues in translating binding to activation. Data show important roles in ligand binding and receptor activation of conserved residues within the transmembrane domain of the GLP-1R. The receptor structural model provides insight into the roles of these residues.
The feasibility of videoconferencing for neuropsychological assessments of rural youth experiencing early psychosis
Authors: Stain Helen J , Payne Kristy , Thienel Renate , Michie Pat , Carr Vaughan , Kelly Brian
Published: August 2011

We conducted a pilot study of the feasibility of videoconferencing as a mode of neuropsychological assessment in young people (14–30 years) from a rural area of New South Wales experiencing early psychosis. All participants ( n = 11) completed assessments both face-to-face and by videoconference at a bandwidth of 384 kbit/s. Assessments included confirmation of diagnosis, quality of life and neurocognitive functioning. There was a strong correlation between modes of assessment for most instruments. Bland-Altman plots indicated that in general the mean difference between face-to-face and videoconference modes of assessment was close to zero with significant bias only evident for general cognitive functioning (WTAR), where videoconferencing produced higher ratings than face-to-face assessments. Feedback from the participants indicated strong acceptability of assessment by videoconferencing, thus supporting further investigation of use of this mode of assessment for clinical and research purposes.
Evaluation of teledermatology adoption by health-care professionals using a modified Technology Acceptance Model
Authors: Orruño Estibalitz , Gagnon Marie Pierre , Asua José , Abdeljelil Anis Ben
Published: August 2011

We examined the main factors affecting the intention of physicians to use teledermatology using a modified Technology Acceptance Model (TAM). The investigation was carried out during a teledermatology pilot study conducted in Spain. A total of 276 questionnaires were sent to physicians by email and 171 responded (62%). Cronbach's alpha was acceptably high for all constructs. Theoretical variables were well correlated with each other and with the dependent variable (Intention to Use). Logistic regression indicated that the original TAM model was good at predicting physicians' intention to use teledermatology and that the variables Perceived Usefulness and Perceived Ease of Use were both significant (odds ratios of 8.4 and 7.4, respectively). When other theoretical variables were added, the model was still significant and it also became more powerful. However, the only significant predictor in the modified model was Facilitators with an odds ratio of 9.9. Thus the TAM was good at predicting physicians' intention to use teledermatology. However, the most important variable was the perception of Facilitators to using the technology (e.g. infrastructure, training and support).
Smartphone applications for pain management
Authors: Rosser Benjamin A , Eccleston Christopher
Published: August 2011

Smartphone applications (or apps) are becoming increasingly popular. The lack of regulation or guidance for health-related apps means that the validity and reliability of their content is unknown. We have conducted a review of available apps relating to the generic condition of pain. The official application stores for five major smartphone platforms were searched: iPhone, Android, Blackberry, Nokia/Symbian and Windows Mobile. Apps were included if they reported a focus on pain education, management or relief, and were not solely aimed at health-care professionals (HCPs). A total of 111 apps met the inclusion criteria. The majority of apps reviewed claimed some information provision or electronic manual component. Diary tracking of pain variables was also a common feature. There was a low level of stated HCP involvement in app development and content. Despite an increasing number of apps being released, the frequency of HCP involvement is not increasing. Pain apps appear to be able to promise pain relief without any concern for the effectiveness of the product, or for possible adverse effects of product use. In a population often desperate for a solution to distressing and debilitating pain conditions, there is considerable risk of individuals being misled.
The use of Hegar's dilator for finding correct planes around the uterus
Authors: Gnanaraj J
Published: August 2011

The Hegar's dilator could be used during both laparoscopic and open surgeries to find the correct planes to enter into either posterior or anterior fornix with minimal blood loss and with ease.
Prevalence of Nocardia species among HIV-positive patients with suspected tuberculosis
Authors: Alnaum Hana M A , Elhassan Mogahid M , Mustafa Faisal Y , Hamid Mohamed E
Published: August 2011

The objective of the study was to determine the frequency of nocardiosis in HIV-positive and HIV-negative individuals clinically suspected of having tuberculosis (TB). The study population ( n = 171) were those who attended chest hospitals in Khartoum State, Sudan, between January and March 2010. The patients suffered from pulmonary infections with positive acid-fast bacilli. Blood ( n = 171) and sputum ( n = 171) samples were collected simultaneously. Blood samples were tested serologically for the presence of antibodies using HIV/Intensified Combination Prevention (ICP) test and sputum were cultured onto Lowenstein Jensen slants according to standard methods. Isolates showing rapid growth characteristic of Nocardiae were subcultured and subsequently identified using glucose yeast extract agar medium. All candidates in the study population ( n = 171) suffered from pulmonary infections, nocardiosis was diagnosed in 4% ( n = 7), HIV-positive cases were 17 (9.9%). Five Nocardia species were isolated from HIV-negative patients whereas two were from HIV-positive patients. Nocardia spp. cause pulmonary infections (4.09%) in both immunocompetent (2.92%) as well as immunocompromised (1.17%) patients who attend chest clinics in Sudan.
Skeletal fluorosis mimicking seronegative spondyloarthropathy: a deceptive presentation
Authors: Kumar Shivanjali , Kakar Atul , Gogia Atul , Byotra S P
Published: August 2011

Skeletal fluorosis is rarely recognized early and is a major cause of morbidity. We report on a 40-year-old man with skeletal fluorosis mimicking seronegative spondyloarthropathy.
Flexural Strength Evaluation for Cold-Formed Steel Lip-Reinforced Built-up I-Beams
Authors: Zhou Xu-Hong , Shi Yu
Published: August 2011

In order to investigate the flexural behavior of cold-formed steel lip-reinforced built-up I-beams, a total of 9 I-beams with three series and 3 identical specimens for each series are tested, and test specimens are simulated by finite element analysis. Results of finite element analysis and experimental results agree well, proving the validity of the finite element method in this paper. Then, substantially parametric analyses are carried out through this finite element model and the following conclusions can be obtained: the steel grade and width-to-thickness ratio of flanges have great influence on the effective width-to-thickness ratio of compression flanges, while the length of the beam, the height-to-thickness ratio of the web, and the thickness of the plate have relatively little influence. Finally, based on results of parametric analyses, effective width method and strength-reduction method on ultimate load-carrying capacity of cold-formed I-beams are proposed. Moreover, tables and equations, which are used to determine the effective width-to-thickness ratios of compressed flanges or strength-reduction factors of built-up I-beams with typical sections, are gained. The ultimate load-carrying capacity from these methods agrees well with experimental results. Therefore, the effective width method and strength-reduction method in this paper are valid and are able to be applied in practice.