bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic review of economic evaluations of interventions to tackle cardiovascular disease in low- and middle-income countries
Authors: Suhrcke Marc , Boluarte Till A , Niessen Louis 
Published: January 2012

Abstract

Background
Low-and middle-income countries are facing both a mounting burden of cardiovascular disease (CVD) as well as severe resource constraints that keep them from emulating some of the extensive strategies pursued in high-income countries. There is thus an urgency to identify and implement those interventions that help reap the biggest reductions of the CVD burden, given low resource levels. What are the interventions to combat CVDs that represent good "value for money" in low-and middle-income countries? This study reviews the evidence-base on economic evaluations of interventions located in those countries.

Methods
We conducted a systematic literature review of journal articles published until 2009, based on a comprehensive key-word based search in generic and specialized electronic databases, accompanied by manual searches of expert databases. The search strategy consisted of freetext and MeSH terms related to economic evaluation and cardiovascular disease. Two independent reviewers verified fulfillment of inclusion criteria and extracted study characteristics.

Results
Thirty-three studies met the selection criteria. We find a growing research interest, in particular in most recent years, if from a very low baseline. Most interventions fall under the category primary prevention, as opposed to case management or secondary prevention. Across the spectrum of interventions, pharmaceutical strategies have been the predominant focus, and, taken at face value, these show significant positive economic evidence, specifically when compared to the counterfactual of no interventions. Only a few studies consider non-clinical interventions, at population level. Almost half of the studies have modelled the intervention effectiveness based on existing risk-factor information and effectiveness evidence from high-income countries.

Conclusion
The cost-effectiveness evidence on CVD interventions in developing countries is growing, but remains scarce, and is biased towards pharmaceutical interventions. While the burden of cardiovascular disease is growing in these countries, future research should put greater emphasis on non-clinical interventions than has hitherto been the case. Significant differences in outcome measures and methodologies prohibit a direct ranking of the interventions by their degree of cost-effectiveness. Considerable caution should be exercised when transferring effectiveness estimates from developed countries for the purpose of modelling cost-effectiveness in developing countries. New local CVD risk factor and intervention follow-up studies are needed. Some pharmaceutical strategies appear cost-effective while clarifications are needed on the diagnostic approach in single high-risk factor vs. absolute risk targeting, the role of patient compliance, and the potential public health consequences of large-scale medicalization.
Health related quality of life among adolescents with premenstrual disorders: a cross sectional study
Authors: Delara Mahin , Ghofranipour Fazlollah , Azadfallah Parviz , Tavafian Sedigheh Sadat , Kazemnejad Anoushirvan , Montazeri Ali 
Published: January 2012

Abstract

Background
Premenstrual disorders usually refer to premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). This study was designed to evaluate health-related quality of life (HRQOL) in a sample of Iranian adolescents with premenstrual disorders.

Methods
This was a cross sectional study. A sample of adolescent schoolgirls aged between 14 and 19 years were included in the study. Premenstrual disorders were indicated according to the International Classification of Diseases (ICD-10) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Health-related quality of life was measured using the Short Form Health Survey (SF-36). The data were analyzed in a descriptive fashion and were compared among subgroups of the study sample.

Results
In all 602 female students were studied. All students reported at least one premenstrual symptom. Of these, 224 (37.2%) met the diagnostic criteria for premenstrual dysphoric disorder (PMDD). Comparing the SF-36 scores between female students with and without PMDD, it was found that there were significant differences between these two groups in all measures (P < 0.001) except for physical functioning (P = 0.274). These differences were more evident on role emotional, role physical, social functioning and bodily pain.

Conclusion
The study findings affirm the fact that adolescents with premenstrual disorders suffer from poor health-related quality of life. In order to improve quality of life in female adolescents appropriate support should be provided for this population especially for those who suffer from more severe premenstrual disorders.
Innate Immunity in multiple sclerosis white matter lesions: expression of natural cytotoxicity triggering receptor 1 (NCR1)
Authors: Durrenberger Pascal F , Ettorre Anna , Kamel Fatemah , Webb Louise V , Sim Malcolm , Nicholas Richard S , Malik Omar , Reynolds Richard , Boyton Rosemary J , Altmann Daniel M 
Published: January 2012

Abstract

Background
Pathogenic or regulatory effects of natural killer (NK) cells are implicated in many autoimmune diseases, but evidence in multiple sclerosis (MS) and its murine models remains equivocal. In an effort to illuminate this, we have here analysed expression of the prototypic NK cell marker, NCR1 (natural cytotoxicity triggering receptor; NKp46; CD335), an activating receptor expressed by virtually all NK cells and therefore considered a pan-marker for NK cells. The only definitive ligand of NCR1 is influenza haemagglutinin, though there are believed to be others. In this study, we investigated whether there were differences in NCR1+ cells in the peripheral blood of MS patients and whether NCR1+ cells are present in white matter lesions.

Results
We first investigated the expression of NCR1 on peripheral blood mononuclear cells and found no significant difference between healthy controls and MS patients. We then investigated mRNA levels in central nervous system (CNS) tissue from MS patients: NCR1 transcripts were increased more than 5 times in active disease lesions. However when we performed immunohistochemical staining of this tissue, few NCR1+ NK cells were identified. Rather, the major part of NCR1 expression was localised to astrocytes, and was considerably more pronounced in MS patients than controls. In order to further validate de novo expression of NCR1 in astrocytes, we used an in vitro staining of the human astrocytoma U251 cell line grown to model whether cell stress could be associated with expression of NCR1. We found up-regulation of NCR1 expression in U251 cells at both the mRNA and protein levels.

Conclusions
The data presented here show very limited expression of NCR1+ NK cells in MS lesions, the majority of NCR1 expression being accounted for by expression on astrocytes. This is compatible with a role of this cell-type and NCR1 ligand/receptor interactions in the innate immune response in the CNS in MS patients. This is the first report of NCR1 expression on astrocytes in MS tissue: it will now be important to unravel the nature of cellular interactions and signalling mediated through innate receptor expression on astrocytes.
Pharmacological inhibition of Akt and downstream pathways modulates the expression of COX-2 and mPGES-1 in activated microglia
Authors: de Oliveira Antonio CP , Candelario-Jalil Eduardo , Langbein Julia , Wendeburg Lena , Bhatia Harsharan S , Schlachetzki Johannes CM , Biber Knut , Fiebich Bernd L 
Published: January 2012

Abstract

Background
Microglia are considered a major target for modulating neuroinflammatory and neurodegenerative disease processes. Upon activation, microglia secrete inflammatory mediators that contribute to the resolution or to further enhancement of damage in the central nervous system (CNS). Therefore, it is important to study the intracellular pathways that are involved in the expression of the inflammatory mediators. Particularly, the role of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and glycogen synthase kinase-3 (GSK-3) pathways in activated microglia is unclear. Thus, in the present study we investigated the role of Akt and its downstream pathways, GSK-3 and mTOR, in lipopolysaccharide (LPS)-activated primary rat microglia by pharmacological inhibition of these pathways in regard to the expression of cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase-1 (mPGES-1) and to the production of prostaglandin (PG) E2 and PGD2.

Findings
We show that inhibition of Akt by the Akt inhibitor X enhanced the production of PGE2 and PGD2 without affecting the expression of COX-2, mPGES-1, mPGES-2 and cytosolic prostaglandin E synthase (cPGES). Moreover, inhibition of GSK-3 reduced the expression of both COX-2 and mPGES-1. In contrast, the mTOR inhibitor rapamycin enhanced both COX-2 and mPGES-1 immunoreactivity and the release of PGE2 and PGD2. Interestingly, NVP-BEZ235, a dual PI3K/mTOR inhibitor, enhanced COX-2 and reduced mPGES-1 immunoreactivity, albeit PGE2 and PGD2 levels were enhanced in LPS-stimulated microglia. However, this compound also increased PGE2 in non-stimulated microglia.

Conclusion
Taken together, we demonstrate that blockade of mTOR and/or PI3K/Akt enhances prostanoid production and that PI3K/Akt, GSK-3 and mTOR differently regulate the expression of mPGES-1 and COX-2 in activated primary microglia. Therefore, these pathways are potential targets for the development of novel strategies to modulate neuroinflammation.
The role of G protein gene GNB3 C825TPolymorphism in HIV-1 acquisition, progression and immune activation
Authors: Juno Jennifer , Tuff Jeffrey , Choi Robert , Card Catherine , Kimani Joshua , Wachihi Charles , Koesters-Kiazyk Sandra , Ball T Blake , Farquhar Carey , Plummer Francis A , John-Stewart Grace , Luo Ma , Fowke Keith R 
Published: January 2012

Abstract

Background
The GNB3 C825T polymorphism is associated with increased G protein-mediated signal transduction, SDF-1α-mediated lymphocyte chemotaxis, accelerated HIV-1 progression, and altered responses to antiretroviral therapy among Caucasian subjects. The GNB3 825T allele is highly prevalent in African populations, and as such any impact on HIV-1 acquisition or progression rates could have a dramatic impact. This study examines the association of the 825T polymorphism with HIV-1 acquisition, disease progression and immune activation in two African cohorts. GNB3 825 genotyping was performed for enrolees in both a commercial sex worker cohort and a perinatal HIV transmission (PHT) cohort in Nairobi, Kenya. Ex vivo immune activation was quantified by flow cytometry, and plasma chemokine levels were assessed by cytokine bead array.

Results

GNB3 genotype was not associated with sexual or vertical HIV-1 acquisition within these cohorts. Within the Pumwani cohort, GNB3 genotype did not affect HIV-1 disease progression among seroconverters or among HIV-1-positive individuals after adjustment for baseline CD4 count. Maternal CD4 decline and viral load increase in the PHT cohort did not differ between genotypes. Multi-parametric flow cytometry assessment of T cell activation (CD69, HLA-DR, CD38) and Treg frequency (CD25+FOXP3+) found no differences between genotype groups. Plasma SDF-1α, MIP-1β and TRAIL levels quantified by cytokine bead array were also similar between groups.

Conclusions
In contrast to previous reports, we were unable to provide evidence to suggest that the GNB3 C825T polymorphism affects HIV-1 acquisition or disease progression within African populations. Ex vivo immune activation and plasma chemokine levels were similarly unaffected by GNB3 genotype in both HIV-1-negative and HIV-1-positive individuals. The paucity of studies investigating the impact of GNB3 polymorphism among African populations and the lack of mechanistic studies make it difficult to assess the true biological significance of this polymorphism in HIV-1 infection.
Functional Characterization and Analgesic Effects of Mixed Cannabinoid Receptor/T-Type Channel Ligands
Authors: You Haitao , Gadotti Vinicius M , Petrov Ravil R , Zamponi Gerald W , Diaz Philippe 
Published: January 2012

Background: Both T-type calcium channels and cannabinoid receptors modulate signalling in the primary afferent pain pathway. Here, we investigate the analgesics activities of a series of novel cannabinoid receptor ligands with T-type calcium channel blocking activity. Results: Novel compounds were characterized in radioligand binding assays and in vitro functional assays at human and rat CB1 and CB2 receptors. The inhibitory effects of these compounds on transient expressed human T-type calcium channels were examined in tsA-201 cells using standard whole-cell voltage clamp techniques, and their analgesic effects in response to various administration routes (intrathecally, intraplantarly, intraperitoneally) assessed in the formalin model. A series of compounds were synthesized and evaluated for channel and receptor activity. Compound NMP-7 acted as non-selective CB1/CB2 agonist while NMP4 was found to be a CB1 partial agonist and CB2 inverse agonist. Furthermore, NMP-144 behaved as a selective CB2 inverse agonist. All of these three compounds completely inhibited peak Cav3.2 currents with IC50 values in the low micromolar range. All compounds mediated analgesic effects in the formalin model, but depending on the route of administration, could differentially affect phase 1 and phase 2 of the formalin response. Conclusions: Our results reveal that a set of novel cannabinioid receptor ligands potently inhibit T-type calcium channels and show analgesic effects in vivo. Our findings suggest possible novel means of mediating pain relief through mixed T-type/cannabinoid receptor ligands.
Determination of cell survival after irradiation via clonogenic assay versus multiple MTT Assay - A comparative study
Authors: Buch Karl , Peters Tanja , Nawroth Thomas , Sänger Markus , Schmidberger Heinz , Langguth Peter 
Published: January 2012

Abstract
For studying proliferation and determination of survival of cancer cells after irradiation, the multiple MTT assay, based on the reduction of a yellow water soluble tetrazolium salt to a purple water insoluble formazan dye by living cells was modified from a single-point towards a proliferation assay. This assay can be performed with a large number of samples in short time using multi-well-plates, assays can be performed semi-automatically with a microplate reader. Survival, the calculated parameter in this assay, is determined mathematically. Exponential growth in both control and irradiated groups was proven as the underlying basis of the applicability of the multiple MTT assay. The equivalence to a clonogenic survival assay with its disadvantages such as time consumption was proven in two setups including plating of cells before and after irradiation. Three cell lines (A 549, LN 229 and F 98) were included in the experiment to study its principal and general applicability.
A versatile toolkit for high throughput functional genomics with Trichoderma reesei
Authors: Schuster André , Bruno Kenneth S , Collett James R , Baker Scott E , Seiboth Bernhard , Kubicek Christian P , Schmoll Monika 
Published: January 2012

Abstract

Background
The ascomycete fungus, Trichoderma reesei (anamorph of Hypocrea jecorina), represents a biotechnological workhorse and is currently one of the most proficient cellulase producers. While strain improvement was traditionally accomplished by random mutagenesis, a detailed understanding of cellulase regulation can only be gained using recombinant technologies.

Results
Aiming at high efficiency and high throughput methods, we present here a construction kit for gene knock out in T. reesei. We provide a primer database for gene deletion using the pyr4, amdS and hph selection markers. For high throughput generation of gene knock outs, we constructed vectors using yeast mediated recombination and then transformed a T. reesei strain deficient in non-homologous end joining (NHEJ) by spore electroporation. This NHEJ-defect was subsequently removed by crossing of mutants with a sexually competent strain derived from the parental strain, QM9414.

Conclusions
Using this strategy and the materials provided, high throughput gene deletion in T. reesei becomes feasible. Moreover, with the application of sexual development, the NHEJ-defect can be removed efficiently and without the need for additional selection markers. The same advantages apply for the construction of multiple mutants by crossing of strains with different gene deletions, which is now possible with considerably less hands-on time and minimal screening effort compared to a transformation approach. Consequently this toolkit can considerably boost research towards efficient exploitation of the resources of T. reesei for cellulase expression and hence second generation biofuel production.
Genomics and proteomics in liver fibrosis and cirrhosis
Authors: Hannivoort Rebekka A , Hernandez-Gea Virginia , Friedman Scott L 
Published: January 2012

AbstractGenomics and proteomics have become increasingly important in biomedical science in the past decade, as they provide an opportunity for hypothesis-free experiments that can yield major insights not previously foreseen when scientific and clinical questions are based only on hypothesis-driven approaches. Use of these tools, therefore, opens new avenues for uncovering physiological and pathological pathways. Liver fibrosis is a complex disease provoked by a range of chronic injuries to the liver, among which are viral hepatitis, (non-) alcoholic steatohepatitis and autoimmune disorders. Some chronic liver patients will never develop fibrosis or cirrhosis, whereas others rapidly progress towards cirrhosis in a few years. This variety can be caused by disease-related factors (for example, viral genotype) or host-factors (genetic/epigenetic). It is vital to establish accurate tools to identify those patients at highest risk for disease severity or progression in order to determine who are in need of immediate therapies. Moreover, there is an urgent imperative to identify non-invasive markers that can accurately distinguish mild and intermediate stages of fibrosis. Ideally, biomarkers can be used to predict disease progression and treatment response, but these studies will take many years due to the requirement for lengthy follow-up periods to assess outcomes. Current genomic and proteomic research provides many candidate biomarkers, but independent validation of these biomarkers is lacking, and reproducibility is still a key concern. Thus, great opportunities and challenges lie ahead in the field of genomics and proteomics, which, if successful, could transform the diagnosis and treatment of chronic fibrosing liver diseases.
A novel deletion in 2q24.1q24.2 in a girl with mental retardation and generalized hypotonia: a case report
Authors: Palumbo Orazio , Palumbo Pietro , Palladino Teresa , Stallone Raffaella , Zelante Leopoldo , Carella Massimo 
Published: January 2012

Abstract

Background
Chromosomal imbalances, recognized as the major cause of mental retardation, are often due to submicroscopic deletions or duplications not evidenced by conventional cytogenetic methods. To date, interstitial deletion of long arm of chromosome 2 have been reported for more than 100 cases, although studies reporting small interstitial deletions involving the 2q24.1q24.2 region are rare. With the widespread clinical use of comparative genomic hybridization chromosomal microarray technology, several cryptic chromosome imbalances have outlined new genotype-phenotype correlations and isolated a number of distinctive clinical conditions.

Results
here we report on a girl with mental retardation and generalized hypotonia. A genome-wide screen for copy number variations (CNVs) using single nucleotide polymorphisms (SNPs) array revealed a 7.5 Mb interstitial deletion of chromosome region 2q24.1q24.2 encompassing 59 genes, which was absent in parents. The gene content analysis of the deleted region and review of the literature revealed the presence of some genes that may be indicated as good candidate in generating the main clinical features of the patient.

Discussion
the present case represents a further patient described in the literature with an interstitial deletion of chromosome 2q24.1q24.2. Our patient shares some clinical features with the previously reported patients carriers of overlapping 2q24 deletion. Although more cases are needed to delineate the full-blown phenotype of 2q24.1q24.2 deletion syndrome, published data and present observation suggest that hemizygosity of this region results in a clinically recognizable phenotype. Considering these clinical and cytogenetic similarities, we suggest the existence of an emerging syndrome associated to 2q24.1q24.2 region.
Loop-mediated isothermal amplification (LAMP): Early detection of Toxoplasma gondii infection in mice
Authors: Kong Qing-Ming , Lu Shao-Hong , Tong Qun-Bo , Lou Di , Chen Rui , Zheng Bin , Kumagai Takashi , Wen Li-Yong , Ohta Nobuo , Zhou Xiao-Nong 
Published: January 2012

Abstract

Background
Toxoplasmosis is a widespread zoonotic parasitic disease that occurs in both animals and humans. Traditional molecular assays are often difficult to perform, especially for the early diagnosis of Toxoplasma gondii infections. Here, we established a novel loop-mediated isothermal amplification targeting the 529 bp repeat element (529 bp-LAMP) to detect T. gondii DNA in blood samples of experimental mice infected with tachyzoites of the RH strain.

Findings
The assay was performed with Bst DNA polymerase at 65°C for 1 h. The detection limit of the 529 bp- LAMP assay was as low as 0.6 fg of T. gondii DNA. The sensitivity of this assay was 100 and 1000 fold higher than that of the LAMP targeting B1 gene (B1-LAMP) and nested PCR targeting 529 bp repeat element (529 bp-nested PCR), respectively. The specificity of the 529 bp- LAMP assay was determined using the DNA samples of Trypanosoma evansi, Plasmodium falciparum, Paragonimus westermani, Schistosoma japonicum, Fasciola hepatica and Angiostrongylus cantonensis. No cross-reactivity with the DNA of any parasites was found. The assay was able to detect T. gondii DNA in all mouse blood samples at one day post infection (dpi).

Conclusions
We report the following findings: (i) The detection limit of the 529 bp- LAMP assay is 0.6 fg of T. gondii DNA; (ii) The assay does not involve any cross-reactivity with the DNA of other parasites; (iii) This is the first report on the application of the LAMP assay for early diagnosis of toxoplasmosis in blood samples from experimentally infected mice. Due to its simplicity, sensitivity and cost-effectiveness for common use, we suggest that this assay should be used as an early diagnostic tool for health control of toxoplasmosis.