bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining the Instrumental–Expressive Continuum of Homicides
Authors: Fox Kathleen A. , Allen Terry
Published: July 2013

The current study examines and extends the instrumental–expressive categories of homicide. Correspondence analysis of 30 years of homicide data from the Federal Bureau of Investigation’s Supplementary Homicide Reports focuses on gender differences, the victim–offender relationship and weapon choice among the types of homicide. Findings reveal that the weapon type used in homicides depends on the sex and relationship of the offender and victim. Results also support a revised instrumental–expressive homicide continuum that includes offensive-defensive categories. The enhanced homicide dimensions include instrumental-offensive, expressive-offensive, and expressive-defensive homicides.
Managing Engagement Behaviors in a Network of Customers and Stakeholders
Authors: Verleye Katrien , Gemmel Paul , Rangarajan Deva
Published: July 2013

Firms striving for long-term profitability need to build stronger customer-firm relationships by getting their customers more engaged with the firm. One path to this end is introducing practices to manage different forms of customer engagement behaviors (CEBs). To develop more effective and efficient CEB management practices, this research proposes and empirically tests a theoretical model on managerial and psychological processes to encourage CEBs that are embedded in a broader network of customers and stakeholders. Based on qualitative and quantitative studies in nursing homes, we demonstrate that organizational support and overall service quality toward significant others influence some forms of CEBs—more particularly feedback and positive word of mouth (WOM) behaviors—through customer affect toward the organization. It is interesting to note that customer affect toward the organization encourages WOM behaviors, while it discourages feedback behaviors. Conversely, managerial processes that increase customer role readiness—such as organizational socialization and support from other customers—were found to have a positive impact on all forms of CEBs. This research helps managers of nursing homes and other services with a broad network of customers and stakeholders to improve existing CEB management practices and develop new CEB management practices that are beneficial for the firm and its stakeholders.
Caloric expenditure assessment among older adults: Criterion validity of a novel accelerometry device
Authors: Stahl Sarah T , Insana Salvatore P
Published: July 2013

Criterion validity of a novel accelerometry device that measures caloric expenditure (Fitbit) was evaluated against a self-report estimation of caloric expenditure (Community Healthy Activities Model Program for Seniors) in older adults. Community Health Activities Model Program for Seniors and Fitbit estimates of total caloric expenditure per day were significantly correlated ( r = .61, p < .05). Bland–Altman plots indicated that 70 percent of participants’ data were within 1 standard deviation of the mean difference between measures. These preliminary findings suggest that the Fitbit may be considered a viable instrument for measuring daily caloric expenditure among older adults. However, further work is required to determine the optimal measurement technique for caloric expenditure among older adults.
The correlation of veiling luminance and unified glare rating with a transfer function
Authors: Jiang C-J , Sun C-C , Chen Y-C , Yang T-H , Chang N
Published: July 2013

This study is based on a general interior lighting installation and discusses the relation between veiling luminance and the unified glare rating. Through curve fitting and a derived formula, a transfer function between veiling luminance and the unified glare rating is generated. This result connects disability glare and discomfort glare within a finite range, where the relation between them is almost linearly dependent. This transfer function has a high accuracy as shown by a comparison between the calculated results and the original data, and is the first to provide a connection between disability glare and discomfort glare.
Adiponectin in coronary heart disease and newly diagnosed impaired glucose tolerance
Authors: Azizi Ghanbari Aline , Dörr Rolf , Spitzer Stefan , Stumpf Juergen , Britz Andreas , Amann-Zalan Ildiko , Lodwig Volker , Ulm Bernhard , Schnell Oliver , Lohmann Tobias
Published: July 2013

Objective:

Adiponectin is produced by adipose tissue and regarded as protective hormone for diabetes and coronary heart disease (CHD). Its role in heart failure is discussed controversially.

Methods:

In this study, 1015 consecutive patients admitted for acute ( n = 149) or elective ( n = 866) coronary angiography were enrolled. Patients with known diabetes mellitus (DM) were excluded. All patients were classified by oral glucose tolerance test (oGTT) according to World Health Organization (WHO) criteria and by the results of coronary angiography as no/minor coronary heart disease (CHD), single-vessel disease (1-VD), double-vessel disease (2-VD) or triple-vessel disease (3-VD), by New York Heart Association (NYHA) criteria and by echocardiography for heart failure. Adiponectin and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were measured in all patients.

Results:

Adiponectin was higher in patients with normal glucose tolerance (NGT) (13.65 ± 10.31 mg/l) compared to impaired glucose tolerance (IGT) (11.12 ± 7.5, p < 0.001) or diabetes (11.22 ± 7.63, p < 0.001). There was a stepwise decrease in adiponectin from no CHD (18.16 ± 12.49 mg/L) to minor CHD (16.01 ± 11.42) to 1-VD (12.18 ± 8.8, p < 0.001 to no/minor CHD) to 2- and 3-VD (10.68 ± 7.5, p < 0.001 to no/minor CHD, p = 0.004 to 1-VD). Patients with heart failure NYHA III (17.4 ± 10.27) had higher adiponectin levels compared to NYHA II (12.94 ± 9.41, p < 0.001 to NYHA III) and NYHA I (10.3 ± 7.75, p < 0.001 to NYHA III/II). In this line, adiponectin levels were positively correlated to NT-proBNP levels ( r = 0.303), and patients with ejection fraction (EF) < 50% had higher adiponectin levels than those with EF > 50% (14.96 ± 4.35 to 11.78 ± 3.71, p = 0.006).

Conclusion:

Adiponectin levels are inversely correlated to progressing CHD and glucose intolerance but positively correlated to increasing heart failure.
Impaired endothelium-dependent skin microvascular function during high-dose atorvastatin treatment in patients with type 1 diabetes
Authors: Tehrani Sara , Mobarrez Fariborz , Lins Per-Eric , Adamson Ulf , Wallén Håkan N , Jörneskog Gun
Published: July 2013

Aims:

The present study investigated the effects of lipid-lowering therapy with atorvastatin on skin microvascular function in patients with type 1 diabetes and dyslipidaemia.

Methods:

Twenty patients received daily treatment with atorvastatin 80 mg or placebo during 2 months in a randomised, double-blind, cross-over study. Forearm skin microcirculation was investigated with laser Doppler perfusion imaging during iontophoresis of acetylcholine and sodium nitroprusside to assess endothelium-dependent and endothelium-independent microvascular reactivity, respectively. Various biochemical markers of endothelial function were also investigated.

Results:

Endothelium-dependent microvascular reactivity decreased during atorvastatin ( p < 0.001), showing a significant treatment effect compared with placebo ( p = 0.04). Atorvastatin treatment was also associated with increased haemoglobin A1C levels from 7.45% to 7.77% ( p = 0.008).

Conclusions:

The present study shows impaired endothelium-dependent skin microvascular function during high-dose atorvastatin treatment in patients with type 1 diabetes, thus implicating a risk for deterioration of microvascular function during such therapy in these patients.
Elevated Galectin-3 Levels in the Serum of Patients With Alzheimer's Disease
Authors: Wang Xuexin , Zhang Shuping , Lin Faliang , Chu Wenzheng , Yue Shouwei
Published: July 2013

Alzheimer’s disease (AD) is a neurodegenerative disorder of the central nervous system. Galectin-3 (Gal-3) is characterized by a conserved sequence within the carbohydrate recognition domain. The effect of Gal-3 in AD is presently unknown. In this study, we found significantly increased Gal-3 serum levels in patients with AD compared to control participants ( P = .017). There was no significant difference between patients with mild cognitive impairment (MCI) and healthy controls ( P = .143) or between patients with AD and MCI ( P = .688). The degree of cognitive impairment, as measured by the Mini-Mental Status Examination score, was found to have a significant correlation with the Gal-3 serum levels in all patients and healthy controls. These data suggest that Gal-3 potentially plays a role in the neuropathogenesis of AD. The Gal-3 found in serum could be a potential candidate for a biomarker panel for AD diagnosis.
Update on platelet glycoprotein IIb/IIIa inhibitors: recommendations for clinical practice
Authors: Muñiz-Lozano Ana , Rollini Fabiana , Franchi Francesco , Angiolillo Dominick J.
Published: July 2013

Antiplatelet therapy is the cornerstone of treatment for patients with acute coronary syndrome (ACS) and undergoing percutaneous coronary intervention (PCI). Glycoprotein IIb/IIIa receptors mediate platelet aggregation, representing the final common pathway of platelet-mediated thrombosis. Therefore, agents blocking this pathway may be desirable for the treatment of patients with ACS and PCI. Glycoprotein IIb/IIIa receptor inhibitors have been widely investigated and have been key to the pharmacological advancements in the field. However, although GPIs have been important to reduce ischemic complications, their elevated risk of bleeding complications remains a major limitation. The poor prognostic implications, including increased mortality, associated with bleeding complication underscores the need for alternative treatment options. Over the past years there have been several advancements in antithrombotic pharmacology which have led to changes in recommendations for GPI usage in clinical practice. This is an overview of the most recent clinical trial data on GPIs, and provides practical insight on their modern day use in ACS therapy.
Large Pericardial Cyst in an Asymptomatic Child
Authors: Loggos S. , Mitropoulos F. , Kondrafouris K. , Milonakis M. , Kanakis M. , Chantzis A. , Bobos D. , Giannopoulos N. , Azariadis P.
Published: July 2013

We present a case report of a nine-year-old asymptomatic girl with a large cystic lesion of the left hemithorax, occupying almost 80% of the left hemithorax, first believed to be a parasitic cyst that was operated and proved to be of parietal pericardial origin. Mediastinal cysts and pericardial cysts in particular are mostly discovered accidentally and so was the case with our patient. The diagnosis included not only clinical examination but also the utilization of computed tomography and magnetic resonance imaging. The only treatment for pericardial cysts is surgical excision and patients recover fully with no complication.
Cardiac Injury in Child Managed Successfully in Underprivileged Hospital of Africa
Authors: Gnassingbé Komla , Simlawo Kpatekana , Egbohou Pilakimwé , Noumedem NGuefack Blanchard , Mama A. Wakatou , Mihluedo-Agbolan Komlan , Akakpo-Numado Komlatsé G. , Tekou Hubert
Published: July 2013

Cardiac injuries are rare and the associated mortality is high. Their prognosis can be ameliorated by early diagnosis and management in a specialized hospital with appropriate resuscitation care. This report describes a case of cardiac penetrating injury in a child managed successfully in an underprivileged hospital of Africa.
Effect of molecular structure on seal ability, flex crack and mechanical properties of linear low-density polyethylene films
Authors: Sadeghi F , Ajji A
Published: July 2013

In this article, three linear low-density polyethylenes having different molecular structures were selected and films were produced from them using a semi-industrial cast film extrusion line. Rheological and gel permeation chromatography measurements were performed on the resins to assess their molecular structure. Mechanical, physical and sealability properties of the films were evaluated and the results were discussed with regard to the molecular structure of the resins. It was found that molecular weight and distribution of short-chain branching (comonomer) on the backbone of polyethylene chains are the main factors that control sealability, flexural cracking and mechanical properties. Placement of comonomer on medium length chains generated crystals with expanded unit cell that show lower melting peak. Sealing was controlled by crystal size distribution, chain diffusion and entanglement formation at the interface. linear low-density polyethylenes with lower melting point and boarder molecular weight distribution showed lower seal and hot tack initiation temperatures. Polydispersity along with molecular weight contributes to toughness and puncture resistance. Flexural cracking resistance was observed to be related to crystallinity, tie chain density and more importantly to the amorphous phase fraction. The amorphous part could absorb flexing energy and hinders crack initiation and propagation. Seal through contamination (caulkability) was found to be related to flowability and elasticity of the melt.
Effect of modified filler surfaces and filler-tethered polymer chains on morphology and physical properties of poly(azo-pyridyl-urethane)/multi-walled carbon nanotube nanocomposites
Authors: Kausar Ayesha , Hussain Syed Tajammul
Published: July 2013

Poly(azo-pyridyl-urethane)/multi-walled carbon nanotube (PAPU/MWCNT) nanocomposites were prepared by first synthesizing polyurethane followed by solution dispersing MWCNT in the matrix. We have used two different MWCNTs: the first set of MWCNT contained carboxylic acid group (MWCNT-COOH) and the second set contained acid chloride group (MWCNT-COCl). Afterward, these MWCNT particles were used in the preparation of PAPU/MWCNT nanocomposites. In the first set of nanocomposites, MWCNT-COOH and PAPU were just physically mixed and were designated as PAPU/MWCNT-A. In the second set of nanocomposites, PAPU chains were tethered onto the surfaces of MWCNT-COCl particles and designated as PAPU/MWCNT-AC. Two types of nanocomposites were thus fabricated, including acid functionalized nanotube-based non-tethered PAPU/MWCNT and acid chloride functionalized MWCNT-based tethered system. We have incorporated hydroxyl end-terminated polyurethane via “ grafting to” approach to acid chloride functional MWCNT through esterification. Fourier transform infrared spectra confirmed that the matrix was covalently attached to sidewalls of nanotube. Various nanotube loading levels and surface-modified groups were considered to regulate mechanical, thermal and electrical performance of PAPU/MWCNT. The experimental results showed that a moderate loading level of 5 wt. % MWCNT produced the maximum tensile strength (63.1 MPa) in tethered nanocomposites, while the presence of surface carboxylation of MWCNT relatively decreased the tensile strength (49.7 MPa). Comparative studies based on scanning and transmission electron microscopy of the chemically bonded samples revealed unique nano-fibriller morphology. Dynamic mechanical analysis of nanocomposite films showed an increased segmental rigidity with Tg of 144–153℃ in the tethered system relative to pristine PAPU (133℃). Addition of acid chloride functional MWCNT also contributed to an enhancement in the conductivity (2.9–4.7 S cm−1), relative to PAPU/carboxylated MWCNT (2.0–2.7 S cm−1).
Financialization and the Three Utopias of Shadow Banking
Authors: Kessler Oliver , Wilhelm Benjamin
Published: July 2013

The shadow banking system has been identified as a central cause of the current economic crisis. In this article we clarify how the concept of shadow banking is used in public reports to inform current debates about its regulation. We argue that the debate on the regulation of shadow banking is based upon three utopias: the search for a homogenization of different regulatory spaces; the focus on a temporality based on always present availability of data; and the assumption of static configurations of actors within the financial system. Finally, we propose an alternative reading of shadow banking based on the concept of financialization. Financialization allows us to link shadow banking to questions of authority and legitimacy in financial markets. The politics of financialization in general and shadow banking in particular are linked to the stabilization of interpretations and fixation of meaning.
The Uneasy Promise of Deposit Insurance: Financial Globalization and the Protection of Savers
Authors: Zimmermann Hubert
Published: July 2013

Institutionalized guarantees of saving deposits are, in addition to financial supervision and the central banks' role as lender of last resort, traditional key instruments of states to ensure the economic security of individuals and the stability of financial systems. As such, they are a crucial fundament of modern political economies. Financial globalization and the financialization of savings have increasingly undermined these safety nets. This article argues that these phenomena have not only led to a new precariousness of individual provisions for the future, but also resulted in a flurry of activities by states to bolster existing arrangements to protect savers. Such efforts will be limited in their effectiveness as long as substantial variations exist among different national protective systems. I argue that such differences can partly be explained by the embeddedness of deposit protection systems in different varieties of financial capitalism. This institutionalist explanation has to be supplemented by a theory of interest group influence which emphasizes how concentrated interests manage to push through their preferences and block reform efforts in the global regime of protecting savers. These entrenched interests make it unlikely that current harmonization efforts, as advanced by the Financial Stability Board and the European Union, will be successful.
Pim2 is required for maintaining multiple myeloma cell growth through modulating TSC2 phosphorylation
Authors: Lu Jing , Zavorotinskaya Tatiana , Dai Yumin , Niu Xiao-Hong , Castillo Joseph , Sim Janet , Yu Jianjun , Wang Yingyun , Langowski John L. , Holash Jocelyn , Shannon Kevin , Garcia Pablo D.
Published: July 2013

Key Points

Pim2 expression is highly elevated in multiple myeloma and is required for multiple myeloma proliferation. Pim2 phosphorylates TSC2 and modulates mTOR-C1 activity to promote multiple myeloma cell proliferation.
Some properties of the sequence space "Equation missing"
Authors: Işik Mahmut , Altin Yavuz , Et Mikail
Published: July 2013

In this paper we define the sequence space "Equation missing" on a seminormed complex linear space by using an Orlicz function. We give various properties and some inclusion relations on this space.

MSC:40A05, 40C05, 40D05.
Next generation sequencing of viral RNA genomes
Authors: Marston Denise A , McElhinney Lorraine M , Ellis Richard J , Horton Daniel L , Wise Emma L , Leech Stacey L , David Dan , de Lamballerie Xavier , Fooks Anthony R
Published: July 2013

Background

With the advent of Next Generation Sequencing (NGS) technologies, the ability to generate large amounts of sequence data has revolutionized the genomics field. Most RNA viruses have relatively small genomes in comparison to other organisms and as such, would appear to be an obvious success story for the use of NGS technologies. However, due to the relatively low abundance of viral RNA in relation to host RNA, RNA viruses have proved relatively difficult to sequence using NGS technologies. Here we detail a simple, robust methodology, without the use of ultra-centrifugation, filtration or viral enrichment protocols, to prepare RNA from diagnostic clinical tissue samples, cell monolayers and tissue culture supernatant, for subsequent sequencing on the Roche 454 platform.

Results

As representative RNA viruses, full genome sequence was successfully obtained from known lyssaviruses belonging to recognized species and a novel lyssavirus species using these protocols and assembling the reads using de novo algorithms. Furthermore, genome sequences were generated from considerably less than 200 ng RNA, indicating that manufacturers’ minimum template guidance is conservative. In addition to obtaining genome consensus sequence, a high proportion of SNPs (Single Nucleotide Polymorphisms) were identified in the majority of samples analyzed.

Conclusions

The approaches reported clearly facilitate successful full genome lyssavirus sequencing and can be universally applied to discovering and obtaining consensus genome sequences of RNA viruses from a variety of sources.
Exceptionally high cumulative percentage of NUMTs originating from linear mitochondrial DNA molecules in the Hydra magnipapillata genome
Authors: Song Shen , Jiang Feng , Yuan Jianbo , Guo Wei , Miao Yongwang
Published: July 2013

Background

In contrast to most animal genomes, mitochondrial genomes in species belonging to the phylum Cnidaria show distinct variations in genome structure, including the mtDNA structure (linear or circular) and the presence or absence of introns in protein-coding genes. Therefore, the analysis of nuclear insertions of mitochondrial sequences (NUMTs) in cnidarians allows us to compare the NUMT content in animals with different mitochondrial genome structures.

Results

NUMT identification in theHydra magnipapillata,Nematostella vectensisandAcropora digitiferagenomes showed that the NUMT density in theH. magnipapillatagenome clearly exceeds that in other two cnidarians with circular mitochondrial genomes. We found thatH. magnipapillatais an exceptional ancestral metazoan with a high NUMT cumulative percentage but a large genome, and its mitochondrial genome linearisation might be responsible for the NUMT enrichment. We also detected the co-transposition of exonic and intronic fragments within NUMTs inN. vectensisand provided direct evidence that mitochondrial sequences can be transposed into the nuclear genome through DNA-mediated fragment transfer. In addition, NUMT expression analyses showed that NUMTs are co-expressed with adjacent protein-coding genes, suggesting the relevance of their biological function.

Conclusions

Taken together, our results provide valuable information for understanding the impact of mitochondrial genome structure on the interaction of mitochondrial molecules and nuclear genomes.
Compound heterozygosity of predicted loss-of-function DESvariants in a family with recessive desminopathy
Authors: McLaughlin Heather M , Kelly Melissa A , Hawley Pamela P , Darras Basil T , Funke Birgit , Picker Jonathan
Published: July 2013

Background

Variants in the desmin gene (DES) are associated with desminopathy; a myofibrillar myopathy mainly characterized by muscle weakness, conduction block, and dilated cardiomyopathy. To date, only ~50 disease-associated variants have been described, and the majority of these lead to dominant-negative effects. However, the complete genotypic spectrum of desminopathy is not well established.

Case presentation

Next-generation sequencing was performed on 51 cardiac disease genes in a proband with profound skeletal myopathy, dilated cardiomyopathy, and respiratory dysfunction. Our analyses revealed compound heterozygous DES variants, both of which are predicted to lead to a loss-of-function. Consistent with recessive inheritance, each variant was identified in an unaffected parent.

Conclusions

This case report serves to broaden the variant spectrum of desminopathies and provides insight into the molecular mechanisms of desminopathy, supporting distinct dominant-negative and loss-of-function etiologies.
Interrogating differences in expression of targeted gene sets to predict breast cancer outcome
Authors: Andres Sarah A , Brock Guy N , Wittliff James L
Published: July 2013

Background

Genomics provides opportunities to develop precise tests for diagnostics, therapy selection and monitoring. From analyses of our studies and those of published results, 32 candidate genes were identified, whose expression appears related to clinical outcome of breast cancer. Expression of these genes was validated by qPCR and correlated with clinical follow-up to identify a gene subset for development of a prognostic test.

Methods

RNA was isolated from 225 frozen invasive ductal carcinomas,and qRT-PCR was performed. Univariate hazard ratios and 95% confidence intervals for breast cancer mortality and recurrence were calculated for each of the 32 candidate genes. A multivariable gene expression model for predicting each outcome was determined using the LASSO, with 1000 splits of the data into training and testing sets to determine predictive accuracy based on the C-index. Models with gene expression data were compared to models with standard clinical covariates and models with both gene expression and clinical covariates.

Results

Univariate analyses revealed over-expression of RABEP1, PGR, NAT1, PTP4A2, SLC39A6, ESR1, EVL, TBC1D9, FUT8, and SCUBE2 were all associated with reduced time to disease-related mortality (HR between 0.8 and 0.91, adjustedp < 0.05), while RABEP1, PGR, SLC39A6, and FUT8 were also associated with reduced recurrence times. Multivariable analyses using the LASSO revealed PGR, ESR1, NAT1, GABRP, TBC1D9, SLC39A6, and LRBA to be the most important predictors for both disease mortality and recurrence. Median C-indexes on test data sets for the gene expression, clinical, and combined models were 0.65, 0.63, and 0.65 for disease mortality and 0.64, 0.63, and 0.66 for disease recurrence, respectively.

Conclusions

Molecular signatures consisting of five genes (PGR, GABRP, TBC1D9, SLC39A6 and LRBA) for disease mortality and of six genes (PGR, ESR1, GABRP, TBC1D9, SLC39A6 and LRBA) for disease recurrence were identified. These signatures were as effective as standard clinical parameters in predicting recurrence/mortality, and when combined, offered some improvement relative to clinical information alone for disease recurrence (median difference in C-values of 0.03, 95% CI of -0.08 to 0.13). Collectively, results suggest that these genes form the basis for a clinical laboratory test to predict clinical outcome of breast cancer.
Foxc2 regulates osteogenesis and angiogenesis of bone marrow mesenchymal stem cells
Authors: You Wulin , Gao Hongwei , Fan Lihong , Duan Dapeng , Wang Chunsheng , Wang Kunzheng
Published: July 2013

Background

The Forkhead/Fox transcription factor Foxc2 is a critical regulator of osteogenesis and angiogenesis of cells. Bone marrow mesenchymal stem cells (BMSCs) have the capacity to differentiate into osteoblasts, chondrocytes, adipocytes, myocytes and fibroblasts. The present study investigates the role of Foxc2 overexpression in osteogenesis and angiogenesis of BMSCs in vitro.

Methods

BMSCs were isolated from SD rat femurs and tibias, and characterized by cell surface antigen identification and osteoblasts and adipocytes differentiation. The cells were transfected with lentiviral Foxc2 (Lv-Foxc2) or green fluorescent protein (Lv-GFP). Seventy hours later, Foxc2 expression was observed using real time-PCR and Western blot. The transfected cells were stained with Alizarin red S or alkaline phosphatase (ALP) after osteogenic induction. Meanwhile, the expression levels of osteocalcin (OCN), Runt-related transcription factor 2 (Runx2), vascular endothelial growth factor (VEGF) and platelet-derived growth factor-β (PDGF-β) were measured by real time-PCR, Western blot and immunostaining.

Results

Results of cell characterization showed that the cells were positive to CD44 (99.56%) and negative to CD34 (0.44%), and could differentiate into osteoblasts and adipocytes. Foxc2 overexpression not only increased the numbers of mineralized nodes and ALP activity, but also enhanced the expressions of Runx2, OCN, VEGF and PDGF-β in transfected BMSCs after osteogenic induction. The effects of Foxc2 on osteogenesis and angiogenesis were significantly different between Lv-Foxc2 transfected BMSCs and Lv-GFP transfected BMSCs (P<0.05). In addition, the MAPK-specific inhibitors, PD98059 and LY294002, blocked the Foxc2-induced regulation of BMSC differentiation.

Conclusions

Foxc2 gene is successfully transfected into BMSCs with stable and high expression. The overexpression of Foxc2 acts on BMSCs to stimulate osteogenesis and angiogenesis. The effect of Foxc2 on angiogenesis of the cells is mediated via activating PI3K and ERK.
Dioxin-like compounds and bone quality in Cree women of Eastern James Bay (Canada): a cross-sectional study
Authors: Paunescu Alexandra-Cristina , Dewailly Éric , Dodin Sylvie , Nieboer Evert , Ayotte Pierre
Published: July 2013

Background

Aboriginal populations living in Canada’s northern regions are exposed to a number of persistent organic pollutants through their traditional diet which includes substantial amounts of predator fish species. Exposure to dioxin-like compounds (DLCs) can cause a variety of toxic effects including adverse effects on bone tissue. This descriptive cross-sectional study was conducted to investigate the relationship between plasma concentrations of DLCs and bone quality parameters in Cree women of Eastern James Bay (Canada).

Methods

Two hundred and forty-nine Cree women from seven communities in Eastern James Bay (Canada), aged 35 to 74 years old, participated in the study. In order to determine the total DLC concentration in plasma samples of participants, we measured the aryl hydrocarbon receptor-mediated transcriptional activity elicited by plasma sample extracts using a luciferase reporter gene assay. Plasma concentrations of mono-ortho-substituted dioxin-like polychlorinated biphenyls (DL-PCBs) 105, 118 and 156 were measured by gas chromatography–mass spectrometry. Bone quality parameters (speed of sound, m/s; broadband ultrasound attenuation, dB/MHz; stiffness index, %) were assessed by quantitative ultrasound at the right calcaneus with the Achilles InSight system. Several factors known to be associated with osteoporosis were documented by questionnaire. Multiple linear regression models were constructed for the three ultrasound parameters.

Results

DL-PCBs 105 and 118 concentrations, but not the global DLC concentration, were inversely associated with the stiffness index, even after adjusting for several confounding factors. The stiffness index (log) decreased by −0.22% (p=0.0414) and −0.04% (p=0.0483) with an increase of one μg/L in plasma concentrations of DL-PCB 105 and DL-PCB 118, respectively. Other factors, including age, height, smoking status, menopausal status and the percentage of omega-6 polyunsaturated fatty acids (PUFAs) in erythrocyte membranes were negatively associated with one of the ultrasound parameters, while the percentage of omega-3 PUFAs in these membranes and levels of physical activity and education were positively associated with them.

Conclusions

Our results show that an increase in plasma concentrations of DL-PCBs 105 and 118 was negatively associated with stiffness index, a measure of bone quality/strength, in women of this population. In addition to environmental contaminants, future studies should also consider PUFA intake as a factor influencing bone quality.
Serum Procalcitonin is a sensitive and specific marker in the diagnosis of septic arthritis and acute osteomyelitis
Authors: Maharajan Karthikeyan , Patro Dilip Kumar , Menon Jagdish , Hariharan Ananthanarayanan Palghat , Parija Sabhash Chandra , Poduval Murali , Thimmaiah Sreenivas
Published: July 2013

Background

Early diagnosis of Acute Osteomyelitis (OM) and Septic Arthritis (SA) is of vital importance to avoid devastating complications. There is no single laboratory marker which is sensitive and specific in diagnosing these infections accurately. Total Count, ESR and CRP are not specific as they can also be elevated in non pyogenic causes of inflammation. Pus Culture and sensitivity is not a true gold standard due to its varied positivity rates (40 – 70%). Serum Procalcitonin (PCT), at0.5 ng/mlis found to be an accurate marker for pyogenic infections. The objectives of this study were to show that PCT is an accurate marker in differentiating Acute Osteomyelitis and Septic Arthritis from viral and non infective inflammatory bone and joint conditions.

Methods

Patients of all age groups (n = 82) with suspected Acute Osteomyelitis and Septic Arthritis were prospectively included in this study. All patients were subjected to TC, CRP, PCT, IgM Dengue, IgM Chikungunya, pus and blood culture and sensitivity. At the end of the study, patients were classified into 3 groups: Group 1 = Confirmed Pyogenic (n = 27); Group 2 = Presumed Pyogenic (n = 21); Group 3 = Non – infective inflammatory (n = 34).

Results

Group 1 has higher mean PCT levels than Group 2 and 3 (p < 0.05). PCT, at0.4 ng/ml, was 85.2% sensitive and 87.3% specific in diagnosing Septic Arthritis and Acute Osteomyelitis. In comparison, PCT at conventional cut – off of0.5 ng/mlis 66.7% sensitive and 91% specific.

Conclusion

Serum Procalcitonin, at a cut – off of0.4 ng/ml, is a sensitive and specific marker in the diagnosis of Septic Arthritis and Acute Osteomyelitis.
Report of the Post Kala-Azar Dermal Leishmaniasis (PKDL) consortium meeting, New Delhi, India, 27–29 June 2012
Authors: Desjeux Philippe , Ghosh Raj Shankar , Dhalaria Pritu , Strub-Wourgaft Nathalie , Zijlstra Ed E
Published: July 2013

Post kala-azar dermal leishmaniasis (PKDL) is a neglected complication of visceral leishmaniasis (VL)―a deadly, infectious disease that claims approximately 20,000 to 40,000 lives every year. PKDL is thought to be a reservoir for transmission of VL, thus, adequate control of PKDL plays a key role in the ongoing effort to eliminate VL. Over the past few years, several expert meetings have recommended that a greater focus on PKDL was needed, especially in South Asia. This report summarizes the Post Kala-Azar Dermal Leishmaniasis Consortium Meeting held in New Delhi, India, 27–29 June 2012. The PKDL Consortium is committed to promote and facilitate activities that lead to better understanding of all aspects of PKDL that are needed for improved clinical management and to achieve control of PKDL and VL. Fifty clinicians, scientists, policy makers, and advocates came together to discuss issues relating to PKDL epidemiology, diagnosis, pathogenesis, clinical presentation, treatment, and control. Colleagues who were unable to attend participated during drafting of the consortium meeting report.
Memantine-induced speech problems in two patients with autistic disorder
Authors: Alaghband-Rad Javad , Nikvarz Naemeh , Tehrani-Doost Mehdi , Ghaeli Padideh
Published: July 2013

Stuttering is a complex speech disorder. There are two forms of stuttering: developmental stuttering and acquired stuttering. Developmental stuttering is a disorder of early childhood but acquired stuttering can develop at any age. Some medications can induce or deteriorate stuttering as an adverse effect. There are several reports of stuttering due to psychotropic drugs. Memantine, a glutamate antagonist used in the treatment of Alzheimer’s disease, has also been studied for the treatment of autism spectrum disorders. This report presents deterioration of stuttering and speech problem in two children with autistic disorder who were receiving memantine. Based on our knowledge, this is the first time these adverse drug reactions have been attributed to memantine. In conclusion clinicians should consider that speech problems including stuttering may be due to the consumption of memantine, especially, in children may be a side effect of memantine especially in children.
Developmental coupling of larval and adult stages in a complex life cycle: insights from limb regeneration in the flour beetle, Tribolium castaneum
Authors: Lee Alison K , Sze Christie C , Kim Elaine R , Suzuki Yuichiro
Published: July 2013

Background

A complex life cycle, such as complete metamorphosis, is a key innovation that can promote diversification of species. The evolution of a morphologically distinct larval stage is thought to have enabled insects to occupy broader ecological niches and become the most diverse metazoan taxon, yet the extent to which larval and adult morphologies can evolve independently remains unknown. Perturbation of larval limb regeneration allows us to generate larval legs and antennae with altered limb morphologies, which may be used to explore the developmental continuity that might exist between larval and adult appendages. In this study, we determined the roles of several appendage patterning transcription factors, abrupt (ab), dachshund (dac), Distal-less (Dll), and spineless (ss), in the red flour beetle, Tribolium castaneum, during larval appendage regeneration. The functions of these genes in regenerating and non-regenerating limbs were compared using RNA interference.

Results

During limb regeneration, dac and ss were necessary to re-pattern the same larval structures as those patterned during embryogenesis. Removal of these two genes led to larval appendage patterning defects that were carried over to the adult legs. Surprisingly, even though maternal knockdown of ab had minimal effects on limb allocation and patterning in the embryo, it was necessary for blastema growth, an earlier phase of regeneration. Finally, knockdown of Dll prevented the blastema-like bumps from re-differentiating into appendages.

Conclusions

Our results suggest that, similar to vertebrates, the re-patterning phase of Tribolium larval limb regeneration relies on the same genes that are used during embryonic limb patterning. Thus, the re-patterning phase of regeneration is likely to be regulated by taxon-specific patterning mechanisms. Furthermore, Ab and Dll appear to play important roles during blastema proliferation and re-differentiation, respectively. Finally, our results show that continuity exists between larval and adult limb patterning, and that larval and adult leg morphologies may be developmentally coupled. Thus, the evolution of imaginal discs may have been a key step towards completely removing any developmental constraints that existed between larval and adult phenotypes.
Cytometric profiling in various clinical forms of multiple sclerosis with respect to CD21+, CD32+, and CD35+ B and T cells
Authors: Zandieh Ali , Izad Maryam , Fakhri Mohammad , Amirifard Hamed , Khazaeipour Zahra , Harirchian Mohammad Hosein
Published: July 2013

Background

We aimed to evaluate the frequency of various types of B and T cells expressing CD21, CD32, and CD35 in multiple sclerosis (MS) clinical courses.

Methods

Peripheral blood mononuclear cell from 30 MS patients (17 relapsing remitting [RRMS], six secondary progressive [SPMS], and seven primary progressive MS [PPMS]) and 18 healthy subjects were analyzed. All patients were in acute attack. Healthy controls were matched for age and gender ratio. The frequencies of various subsets of B and T cells were determined using flow cytometry.

Results

The frequency of CD4+T cells was lower in MS patients compared to control subjects (41.14 ± 9.45% vs. 46.88 ± 6.98%, respectively,P < 0.05). The CD32+fraction of CD4+T cells and the CD21+fraction of CD8+T cells were higher in MS patients (2.85 ± 3.72% vs. 1.06 ± 0.62% for CD32+CD4+T cells, 2.71 ± 1.86% vs. 1.16 ± 0.99% for CD21+CD8+T cells in MS patients and control subjects, respectively,P < 0.05). After dividing subjects by type of MS course, higher values of these two T cell subsets were found in SPMS patients compared to control subjects (P < 0.05). Further, RRMS patients had lower levels of CD32+CD4+T cells than SPMS patients and also they had lower levels of CD32+CD8+T cells than PPMS patients (P < 0.05). However, neither the expression of CD35 on T cells nor the various B cell subsets were statistically different between the compared groups.

Conclusions

Our findings demonstrate that T cell subsets expressing CD21 and CD32 may differ with respect to the presence or clinical forms of MS disease. By contrast, CD35+T cells and different subsets of B cells are not altered in various MS clinical courses.
Notch activation stimulates migration of breast cancer cells and promotes tumor growth
Authors: Bolós Victoria , Mira Emilia , Martínez-Poveda Beatriz , Luxán Guillermo , Cañamero Marta , Martínez-A Carlos , Mañes Santos , de la Pompa José Luis
Published: July 2013

Introduction

Dysregulated NOTCH receptor activity has been implicated in breast cancer but the mechanisms by which NOTCH contributes to transformation are not yet clear, as it has context-dependent effects on the properties of transformed cells.

Methods

We have used various in vitro and in vivo carcinogenic models to analyze the impact of Notch signaling in the onset and progression of breast tumors.

Results

We found that ectopic expression of the Notch1 intracellular domain (N1ICD) in MCF-7 breast adenocarcinoma cell line caused reduction and delocalization of E-CADHERIN levels and increased migratory and invasive abilities. Notch inhibition in the invasive breast cancer cell line MDA-MB-231 resulted in increased E-CADHERIN expression and a parallel reduction in their invasive capacity. The growth of subcutaneous xenografts produced with MCF-7 cells was boosted after N1ICD induction, in a cell autonomous manner. In vivo Notch1 activation in the mammary gland using the MMTV-Cre driver caused the formation of papillary tumors that showed increased Hes1 and Hey1 expression and delocalized E-cadherin staining.

Conclusions

These results confirm NOTCH1 as a signal triggering epithelial-mesenchymal transition in epithelial cancer cells, which may have implications in tumor dissemination, metastasis and proliferation in vivo. The identification of specific factors interacting with NOTCH signaling could thus be relevant to fully understanding the role of NOTCH in breast neoplasia.
Human umbilical cord mesenchymal stem cell-derived neuron-like cells rescue memory deficits and reduce amyloid-beta deposition in an AβPP/PS1 transgenic mouse model
Authors: Yang Hui , Xie Zhao Hong , Wei Li Fei , Yang Hong Na , Yang Shao Nan , Zhu Zheng Yu , Wang Ping , Zhao Cui Ping , Bi Jian Zhong
Published: July 2013

Introduction

Cell therapy is a potential therapeutic approach for neurodegenerative disorders, such as Alzheimer disease (AD). Neuronal differentiation of stem cells before transplantation is a promising procedure for cell therapy. However, the therapeutic impact and mechanisms of action of neuron-like cells differentiated from human umbilical cord mesenchymal stem cells in AD have not been determined.

Methods

In this study, we used tricyclodecan-9-yl-xanthogenate (D609) to induce human mesenchymal stem cells isolated from Wharton jelly of the umbilical cord (HUMSCs) to differentiate into neuron-like cells (HUMSC-NCs), and transplanted the HUMSC-NCs into an AβPP/PS1 transgenic AD mouse model. The effects of HUMSC-NC transplantation on the cognitive function, synapsin I level, amyloid β-peptides (Aβ) deposition, and microglial function of the mice were investigated.

Results

We found that transplantation of HUMSC-NCs into AβPP/PS1 mice improved the cognitive function, increased synapsin I level, and significantly reduced Aβ deposition in the mice. The beneficial effects were associated with “alternatively activated” microglia (M2-like microglia). In the mice transplanted with HUMSC-NCs, M2-like microglial activation was significantly increased, and the expression of antiinflammatory cytokine associated with M2-like microglia, interleukin-4 (IL-4), was also increased, whereas the expression of proinflammatory cytokines associated with classic microglia (M1-like microglia), including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), was significantly reduced. Moreover, the expression of Aβ-degrading factors, insulin-degrading enzyme (IDE) and neprilysin (NEP), was increased substantially in the mice treated with HUMSC-NCs.

Conclusions

HUMSC-NC transplantation decreased Aβ deposition and improved memory in AβPP/PS1 mice by a mechanism associated with activating M2-like microglia and modulating neuroinflammation. Transplantation of neuron-like cells differentiated from mesenchymal stem cells might be a promising cell therapy for Alzheimer disease.
Comparison of PAM50 Risk of Recurrence Score With Oncotype DX and IHC4 for Predicting Risk of Distant Recurrence After Endocrine Therapy
Authors: Dowsett Mitch , Sestak Ivana , Lopez-Knowles Elena , Sidhu Kalvinder , Dunbier Anita K. , Cowens J. Wayne , Ferree Sean , Storhoff James , Schaper Carl , Cuzick Jack
Published: July 2013

Purpose

Risk of distant recurrence (DR) among women with estrogen receptor (ER) –positive early breast cancer is the major determinant of recommendations for or against chemotherapy. It is frequently estimated using the Oncotype DX recurrence score (RS). The PAM50 risk of recurrence (ROR) score provides an alternative approach, which also identifies intrinsic subtypes.

Patients and Methods

mRNA from 1,017 patients with ER-positive primary breast cancer treated with anastrozole or tamoxifen in the ATAC trial was assessed for ROR using the NanoString nCounter. Likelihood ratio (LR) tests and concordance indices (c indices) were used to assess the prognostic information provided beyond that of a clinical treatment score (CTS) by RS, ROR, or IHC4, an index of DR risk derived from immunohistochemical assessment of ER, progesterone receptor, human epidermal growth factor receptor 2 (HER2), and Ki67.

Results

ROR added significant prognostic information beyond CTS in all patients (Δ LR-χ2 = 33.9; P < .001) and in all four subgroups: node negative, node positive, HER2 negative, and HER2 negative/node negative; more information was added by ROR than by RS. C indices in the HER2-negative/node-negative subgroup were 0.73, 0.76, and 0.78 for CTS, CTS plus RS, and CTS plus ROR, respectively. More patients were scored as high risk and fewer as intermediate risk by ROR than by RS. Relatively similar prognostic information was added by ROR and IHC4 in all patients but more by ROR in the HER2-negative/node-negative group.

Conclusion

ROR provides more prognostic information in endocrine-treated patients with ER-positive, node-negative disease than RS, with better differentiation of intermediate- and higher-risk groups.
Translation of CGA codon repeats in yeast involves quality control components and ribosomal protein L1
Authors: Letzring Daniel P. , Wolf Andrew S. , Brule Christina E. , Grayhack Elizabeth J.
Published: July 2013

Translation of CGA codon repeats in the yeast Saccharomyces cerevisiae is inefficient, resulting in dose-dependent reduction in expression and in production of an mRNA cleavage product, indicative of a stalled ribosome. Here, we use genetics and translation inhibitors to understand how ribosomes respond to CGA repeats. We find that CGA codon repeats result in a truncated polypeptide that is targeted for degradation by Ltn1, an E3 ubiquitin ligase involved in nonstop decay, although deletion of LTN1 does not improve expression downstream from CGA repeats. Expression downstream from CGA codons at residue 318, but not at residue 4, is improved by deletion of either ASC1 or HEL2, previously implicated in inhibition of translation by polybasic sequences. Thus, translation of CGA repeats likely causes ribosomes to stall and exploits known quality control systems. Expression downstream from CGA repeats at amino acid 4 is improved by paromomycin, an aminoglycoside that relaxes decoding specificity. Paromomycin has no effect if native tRNAArg(ICG) is highly expressed, consistent with the idea that failure to efficiently decode CGA codons might occur in part due to rejection of the cognate tRNAArg(ICG). Furthermore, expression downstream from CGA repeats is improved by inactivation of RPL1B, one of two genes encoding the universally conserved ribosomal protein L1. The effects of rpl1b-Δ and of either paromomycin or tRNAArg(ICG) on CGA decoding are additive, suggesting that the rpl1b-Δ mutant suppresses CGA inhibition by means other than increased acceptance of tRNAArg(ICG). Thus, inefficient decoding of CGA likely involves at least two independent defects in translation.