bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correction of vitamin D deficiency in critically ill patients - VITdAL@ICU study protocol of a double-blind, placebo-controlled randomized clinical trial
Authors: Amrein Karin , Schnedl Christian , Berghold Andrea , Pieber Thomas R , Dobnig Harald 
Published: November 2012

Abstract

Background
Vitamin D deficiency is associated with multiple adverse health outcomes including increased morbidity and mortality in the general population and in critically ill patients. However, no randomized controlled trial has evaluated so far whether treatment with sufficiently large doses of vitamin D can improve clinical outcome of patients in an intensive care setting.

Methods/design
The VITdAL@ICU trial is an investigator-initiated, non-commercial, double-blind, placebo-controlled randomized clinical trial. This study compares high-dose oral cholecalciferol (vitamin D3) versus placebo treatment in a mixed population of 480 critically ill patients with low 25-hydroxyvitamin-D levels at study enrollment (≤ 20ng/ml). Following an initial loading dose of 540,000 IU of vitamin D3, patients receive 90,000 IU of vitamin D3 on a monthly basis for 5 months. The study is designed to compare clinical outcome in the two study arms with the primary endpoint being length of hospital stay. Secondary endpoints include among others length of ICU stay, the percentage of patients with 25(OH)D levels > 30 ng/ml at day 7, ICU and hospital mortality and duration of mechanical ventilation. We describe here the VITdAL@ICU study protocol for the primary report.

Discussion
This trial is designed to evaluate whether high-dose vitamin D3 is able to improve morbidity and mortality in a mixed population of adult critically ill patients and correct vitamin D deficiency safely.

Trial registration
ClinicalTrials: NCT01130181
Associations of the FTO rs9939609 and the MC4R rs17782313 polymorphisms with type 2 diabetes are modulated by diet, being higher when adherence to the Mediterranean diet pattern is low
Authors: Ortega-Azorín Carolina , Sorlí Jose V , Asensio Eva M , Coltell Oscar , Martínez-González Miguel Ángel , Salas-Salvadó Jordi , Covas Maria-Isabel , Arós Fernando , Lapetra José , Serra-Majem Lluís , Gómez-Gracia Enrique , Fiol Miquel , Sáez-Tormo Guillermo , Pintó Xavier , Muñoz Miguel Angel , Ros Emilio , Ordovás Jose M , Estruch Ramon , Corella Dolores 
Published: November 2012

Abstract

Background
Although the Fat Mass and Obesity (FTO) and Melanocortin-4 Receptor (MC4R) genes have been consistently associated with obesity risk, the association between the obesity-risk alleles with type 2 diabetes is still controversial. In some recent meta-analyses in which significant results have been reported, the associations disappeared after adjustment for body mass index (BMI). However gene-diet interactions with dietary patterns have not been investigated. Our main aim was to analyze whether these associations are modulated by the level of adherence to the Mediterranean Diet (MedDiet).

Methods
Case-control study in 7,052 high cardiovascular risk subjects (3,430 type 2 diabetes cases and 3,622 non-diabetic subjects) with no differences in BMI. Diet was assessed by validated questionnaires. FTO-rs9939609 and MC4R-rs17782313 were determined. An aggregate genetic score was calculated to test additive effects. Gene-diet interactions were analyzed.

Results
Neither of the polymorphisms was associated with type 2 diabetes in the whole population. However, we found consistent gene-diet interactions with adherence to the MedDiet both for the FTO- rs9939609 (P-interaction=0.039), the MC4R-rs17782313 (P-interaction=0.009) and for their aggregate score (P-interaction=0.006). When adherence to the MedDiet was low, carriers of the variant alleles had higher type 2 diabetes risk (OR=1.21, 95%CI: 1.03-1.40; P=0.019 for FTO- rs9939609 and OR=1.17, 95%CI:1.01-1.36; P=0.035 for MC4R-rs17782313) than wild-type subjects. However, when adherence to the MedDiet was high, these associations disappeared (OR=0.97, 95%CI: 0.85-1.16; P=0.673 for FTO- rs9939609 and OR=0.89, 95%CI:0.78-1.02; P=0.097 for MC4R-rs17782313). These gene-diet interactions remained significant even after adjustment for BMI. As MedDiet is rich in folate, we also specifically examined folate intake and detected statistically significant interaction effects on fasting plasma glucose concentrations in non-diabetic subjects. However these findings should be interpreted with caution because folate intake may simply reflect a healthy dietary pattern.

Conclusions
These novel results suggest that the association of the FTO-rs9939609 and the MC4R-rs17782313 polymorphisms with type 2 diabetes depends on diet and that a high adherence to the MedDiet counteracts the genetic predisposition.
Design and testing of a synthetic biology framework for genetic engineering of Corynebacterium glutamicum
Authors: Ravasi Pablo , Peiru Salvador , Gramajo Hugo , Menzella Hugo G 
Published: November 2012

Abstract

Background
Synthetic biology approaches can make a significant contribution to the advance of metabolic engineering by reducing the development time of recombinant organisms. However, most of synthetic biology tools have been developed for Escherichia coli. Here we provide a platform for rapid engineering of C. glutamicum, a microorganism of great industrial interest. This bacteria, used for decades for the fermentative production of amino acids, has recently been developed as a host for the production of several economically important compounds including metabolites and recombinant proteins because of its higher capacity of secretion compared to traditional bacterial hosts like E. coli. Thus, the development of modern molecular platforms may significantly contribute to establish C. glutamicum as a robust and versatile microbial factory.

Results
A plasmid based platform named pTGR was created where all the genetic components are flanked by unique restriction sites to both facilitate the evaluation of regulatory sequences and the assembly of constructs for the expression of multiple genes. The approach was validated by using reporter genes to test promoters, ribosome binding sites, and for the assembly of dual gene operons and gene clusters containing two transcriptional units. Combinatorial assembly of promoter (tac, cspB and sod) and RBS (lacZ, cspB and sod) elements with different strengths conferred clear differential gene expression of two reporter genes, eGFP and mCherry, thus allowing transcriptional “fine-tuning”of multiple genes. In addition, the platform allowed the rapid assembly of operons and genes clusters for co-expression of heterologous genes, a feature that may assist metabolic pathway engineering.

Conclusions
We anticipate that the pTGR platform will contribute to explore the potential of novel parts to regulate gene expression, and to facilitate the assembly of genetic circuits for metabolic engineering of C. glutamicum. The standardization provided by this approach may provide a means to improve the productivity of biosynthetic pathways in microbial factories for the production of novel compounds.
ATP and luciferase assays to determine the rate of drug action in in vitro cultures of Plasmodium falciparum
Authors: Khan Tasmiyah , van Brummelen Anna C , Parkinson Christopher J , Hoppe Heinrich C 
Published: November 2012

Abstract

Background
Knowledge of the rate of action of compounds against cultured malaria parasites is required to determine the optimal time-points for drug mode of action studies, as well as to predict likely in vivo parasite clearance rates in order to select optimal hit compounds for further development. In this study, changes in parasite ATP levels and transgenic luciferase reporter activity were explored as means to detect drug-induced stress in cultured parasites.

Methods

In vitro cultures of Plasmodium falciparum 3D7 wild-type or firefly luciferase-expressing parasites were incubated with a panel of six anti-malarial compounds for 10 hours and parasite ATP levels or luciferase activity determined at two-hour intervals using luminescence-based reagents. For comparative purposes, parasite morphology changes were evaluated by light microscopy, as well as the extent to which parasites recover after 48 hours from a six-hour drug treatment using a parasite lactate dehydrogenase assay.

Results
Changes in parasite ATP levels displayed three phenotypes: mild or no change (chloroquine, DFMO); 2–4 fold increase (mefloquine, artemisinin); severe depletion (ritonavir, gramicidin). The respective phenotypes and the rate at which they manifested correlated closely with the extent to which parasites recovered from a six-hour drug treatment (with the exception of chloroquine) and the appearance and severity of morphological changes observed by light microscopy. Luciferase activity decreased profoundly in parasites treated with mefloquine, artemisinin and ritonavir (34-67% decrease in 2 hours), while chloroquine and DFMO produced only mild changes over 10 hours. Gramicidin yielded intermediate decreases in luciferase activity.

Conclusions
ATP levels and luciferase activity respond rapidly to incubation with anti-malarial drugs and provide quantitative read-outs to detect the appearance and magnitude of drug-induced stress in cultured parasites. The correlation between the observed changes and irreversible parasite toxicity is not yet sufficiently clear to predict clinical clearance rates, but may be useful for ranking compounds against each other and standard drugs vis-à-vis rate of action and for determining early time-points for drug mode of action studies.
Enhanced nanoscale resistive switching memory characteristics and switching mechanism using high-Ge-content Ge0.5Se0.5 solid electrolyte
Authors: Rahaman Sheikh Ziaur , Maikap Siddheswar , Das Atanu , Prakash Amit , Wu Ya Hsuan , Lai Chao-Sung , Tien Ta-Chang , Chen Wei-Su , Lee Heng-Yuan , Chen Frederick T , Tsai Ming-Jinn , Chang Liann-Be 
Published: November 2012

Abstract
We demonstrate enhanced repeatable nanoscale bipolar resistive switching memory characteristics in Al/Cu/Ge0.5Se0.5/W, as compared with Al/Cu/Ge0.2Se0.8/W structures, including stable AC endurance (>105 cycles), larger average SET voltage (approximately 0.6 V), excellent data retention (>105 s) at 85°C, and a high resistance ratio (>104) with a current compliance of 8 μA and a small operation voltage of ±1.5 V. A small device size of 150 × 150 nm2 and a Cu nanofilament with a small diameter of 30 nm are both observed by high-resolution transmission electron microscope in the SET state. The Ge
x
Se1 − x
solid electrolyte compositions are confirmed by both energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy. The switching mechanism relies on the smaller barrier heights for holes rather than for electrons; the positively charged Cu
z+ ions (i.e., holes) migrate through the defects in the Ge
x
Se1 − x
solid electrolytes during SET/RESET operations. Hence, the Cu nanofilament starts to grow at the Ge0.5Se0.5/W interface, and starts to dissolve at the Cu/Ge0.5Se0.5 interface, as illustrated in the energy band diagrams. Owing to both the higher barrier for hole injection at the Cu/Ge0.5Se0.5 interface than at the Cu/Ge0.2Se0.8 interface and greater thermal stability, the resistive switching memory characteristics of the Al/Cu/Ge0.5Se0.5/W are improved relative to the Al/Cu/Ge0.2Se0.8/W devices. The Al/Cu/Ge0.5Se0.5/W memory device can also be operated with a low current compliance of 1 nA, and hence, a low SET/RESET power of 0.61 nW/6.4 pW is achieved. In addition, a large memory size of 1,300 Pbit/in2 is achieved with a small nanofilament diameter of 0.25 Å for a small current compliance of 1 nA.
A review of methods for detect human Papillomavirusinfection
Authors: Abreu André L P , Souza Raquel P , Gimenes Fabrícia , Consolaro Marcia E L 
Published: November 2012

Abstract
Human Papillomavirus (HPV) is the most common sexually transmitted virus. Worldwide, the most common high-risk (HR)-HPV are -16/18, and approximately 70% of cervical cancers (CC) are due to infection by these genotypes. Persistent infection by HR-HPV is a necessary but not sufficient cause of this cancer, which develops over a long period through precursor lesions, which can be detected by cytological screening. Although this screening has decreased the incidence of CC, HPV-related cervical disease, including premalignant and malignant lesions, continues to be a major burden on health-care systems. Although not completely elucidated, the HPV-driven molecular mechanisms underlying the development of cervical lesions have provided a number of potential biomarkers for both diagnostic and prognostic use in the clinical management of women with HPV-related cervical disease, and these biomarkers can also be used to increase the positive predictive value of current screening methods. In addition, they can provide insights into the biology of HPV-induced cancer and thus lead to the development of nonsurgical therapies. Considering the importance of detecting HPV and related biomarkers, a variety of methods are being developed for these purposes. This review summarizes current knowledge of detection methods for HPV, and related biomarkers that can be used to discriminate lesions with a high risk of progression to CC.
Expression of Nav1.7 in DRG Neurons Extends from Peripheral Terminals in the Skin to Central Preterminal Branches and Terminals in the Dorsal Horn
Authors: Black Joel A , Frézel Noémie , Dib-Hajj Sulayman D , Waxman Stephen G 
Published: November 2012

Background: Sodium channel Nav1.7 has emerged as a target of considerable interest in pain research, since loss-of-function mutations in SCN9A, the gene that encodes Nav1.7, are associated with a syndrome of congenital insensitivity to pain, gain-of-function mutations are linked to the debiliting chronic pain conditions erythromelalgia and paroxysmal extreme pain disorder, and upregulated expression of Nav1.7 accompanies pain in diabetes and inflammation. Since Nav1.7 has been implicated as playing a critical role in pain pathways, we examined by immunocytochemical methods the expression and distribution of Nav1.7 in rat dorsal root ganglia neurons, from peripheral terminals in the skin to central terminals in the spinal cord dorsal horn. Results: Nav1.7 is robustly expressed within the somata of peptidergic and non-peptidergic DRG neurons, and along the peripherally- and centrally-directed C-fibers of these cells. Nav1.7 is also expressed at nodes of Ranvier in a subpopulation of Aδ-fibers within sciatic nerve and dorsal root. The peripheral terminals of DRG neurons within skin, intraepidermal nerve fibers (IENF), exhibit robust Nav1.7 immunolabeling. The central projections of DRG neurons in the superficial lamina of spinal cord dorsal horn also display Nav1.7 immunoreactivity which extends to presynaptic terminals. Conclusions: The expression of Nav1.7 in DRG neurons extends from peripheral terminals in the skin to preterminal central branches and terminals in the dorsal horn. These data support a major contribution for Nav1.7 in pain pathways, including action potential electrogenesis, conduction along axonal trunks and depolarization/invasion of presynaptic axons. The findings presented here may be important for pharmaceutical development, where target engagement in the right compartment is essential.
Room-temperature super-extraction system (RTSES) optimizes the anxiolytic- and antidepressant-like behavioural effects of traditional Xiao-Yao-San in mice
Authors: Yin Shih-Hsi , Wang Ching-Cheng , Cheng Tain-Junn , Chang Chia-Yu , Lin Kao-Chang , Kan Wei-Chih , Wang Hsien-Yi , Kao Wenny Mei-Wen , Kuo Yen-Liang , Chen Jian-Chyi , Li Shun-Lai , Cheng Chia-Hui , Chuu Jiunn-Jye 
Published: November 2012

Abstract

Background

Xiao-Yao-San (XYS) is a Chinese medicinal formula for treating anxiety and depression. This study aims to evaluate the use of a room-temperature super-extraction system (RTSES) to extract the major active components of XYS and enhance their psycho-pharmacological effects.

Methods
The neuroprotective roles of XYS/RTSES against reserpine-derived neurotoxicity were evaluated using a glial cell injury system (in vitro) and a depression-like C57BL/6 J mouse model (in vivo). The anxiolytic-behavioural effects were measured by the elevated plus-maze (EPM) test and the antidepressant effects were evaluated by the forced swimming test (FST) and tail suspension test (TST). Glucose tolerance and insulin resistance were assayed by ELISA. The expression of 5-HT1A receptors in the prefrontal cortex was examined by western blotting.

Results
XYS/RTSES (300 μg/mL) diminished reserpine-induced glial cell death more effectively than either XYS (300 μg/mL) or fluoxetine (30 μM) at 24 h (P = 0.0481 and P = 0.054, respectively). Oral administration of XYS/RTSES (500 mg/kg/day) for 4 consecutive weeks significantly elevated the ratios of entries (open arms/closed arms; P = 0.0177) and shuttle activity (P = 0.00149) on the EPM test, and reduced the immobility time by 90% on the TST (P = 0.00000538) and FST (P = 0.0000053839). XYS/RTSES also improved the regulation of blood glucose (P = 0.0305) and increased the insulin sensitivity (P = 0.0093). The Western blot results indicated that the activation of cerebral 5-HT1A receptors may be involved in the mechanisms of XYS/RTSES actions.

Conclusion
The RTSES could provide a novel method for extracting effective anxiolytic- and antidepressant-like substances. XYS/RTSES improved the regulation of blood glucose and increased the insulin sensitivity in reserpine-induced anxiety and depression. Neuroprotection of glial cells and activation of cerebral 5-HT1A receptors were also involved.
Lessons learned obtaining informed consent in research with vulnerable populations in community health center settings
Authors: Riden Heather E , Grooms Kya N , Clark Cheryl R , Cohen Laura R , Gagne Josh , Tovar Dora A , Ommerborn Mark J , Orton Piper S , Johnson Paula A 
Published: November 2012

Abstract

Background
To improve equity in access to medical research, successful strategies are needed to recruit diverse populations. Here, we examine experiences of community health center (CHC) staff who guided an informed consent process to overcome recruitment barriers in a medical record review study.

Methods
We conducted ten semi-structured interviews with CHC staff members. Interviews were audiotaped, transcribed, and structurally and thematically coded. We used NVivo, an ethnographic data management software program, to analyze themes related to recruitment challenges.

Results
CHC interviewees reported that a key challenge to recruitment included the difficult balance between institutional review board (IRB) requirements for informed consent, and conveying an appropriate level of risk to patients. CHC staff perceived that the requirements of IRB certification itself posed a barrier to allowing diverse staff to participate in recruitment efforts. A key barrier to recruitment also included the lack of updated contact information on CHC patients. CHC interviewees reported that the successes they experienced reflected an alignment between study aims and CHC goals, and trusted relationships between CHCs and staff and the patients they recruited.

Conclusions
Making IRB training more accessible to CHC-based staff, improving consent form clarity for participants, and developing processes for routinely updating patient information would greatly lower recruitment barriers for diverse populations in health services research.
Phylogenetic relationship of the Brazilian isolates of the rat lungworm Angiostrongylus cantonensis (Nematoda: Metastrongylidae) employing mitochondrial COI gene sequence data
Authors: Monte Tainá C C , Simões Raquel O , Oliveira Ana Paula M , Novaes Clodoaldo F , Thiengo Silvana C , Silva Alexandre J , Estrela Pedro C , Júnior Arnaldo Maldonado 
Published: November 2012

Abstract

Background
The rat lungworm Angiostrongylus cantonensis can cause eosinophilic meningoencephalitis in humans. This nematode’s main definitive hosts are rodents and its intermediate hosts are snails. This parasite was first described in China and currently is dispersed across several Pacific islands, Asia, Australia, Africa, some Caribbean islands and most recently in the Americas. Here, we report the genetic variability among A. cantonensis isolates from different geographical locations in Brazil using mitochondrial cytochrome c oxidase subunit I (COI) gene sequences.

Methods
The isolates of A. cantonensis were obtained from distinct geographical locations of Brazil. Genomic DNAs were extracted, amplified by polymerase reaction, purified and sequenced. A partial sequence of COI gene was determined to assess their phylogenetic relationship.

Results
The sequences of A. cantonensis were monophyletic. We identified a distinct clade that included all isolates of A. cantonensis from Brazil and Asia based on eight distinct haplotypes (ac1, ac2, ac3, ac4, ac5, ac6, ac7 and ac8) from a previous study. Interestingly, the Brazilian haplotype ac5 is clustered with isolates from Japan, and the Brazilian haplotype ac8 from Rio de Janeiro, São Paulo, Pará and Pernambuco states formed a distinct clade. There is a divergent Brazilian haplotype, which we named ac9, closely related to Chinese haplotype ac6 and Japanese haplotype ac7.

Conclusion
The genetic variation observed among Brazilian isolates supports the hypothesis that the appearance of A. cantonensis in Brazil is likely a result of multiple introductions of parasite-carrying rats, transported on ships due to active commerce with Africa and Asia during the European colonization period. The rapid spread of the intermediate host, Achatina fulica, also seems to have contributed to the dispersion of this parasite and the infection of the definitive host in different Brazilian regions.