bluuebunny/crossref_metadata_2025_split huggingface dataset:
The common FTOvariant rs9939609 is not associated with BMI in a longitudinal study on a cohort of Swedish men born 1920-1924
Authors: Jacobsson Josefin A , Risérus Ulf , Axelsson Tomas , Lannfelt Lars , Schiöth Helgi B , Fredriksson Robert 
Published: December 2009

Abstract

Background
Common FTO (fat mass and obesity associated) gene variants have recently been strongly associated with body mass index and obesity in several large studies. Here we set out to examine the association of the FTO variant rs9939609 with BMI in a 32 year follow up study of men born 1920-1924. Moreover, we analyzed the effect of physical activity on the different genotypes.

Methods
The FTO rs9936609 was genotyped using an Illumina golden gate assay. BMI was calculated using standard methods and body fat was estimated by measuring skinfold thickness using a Harpenden caliper. Physical activity was assessed using a four question medical questionnaire.

Results

FTO rs9939609 was genotyped in 1153 elderly Swedish men taking part of a population-based cohort study, the ULSAM cohort. The risk of obesity and differences in BMI according to genotype at the ages of 50, 60, 70, 77 and 82 were investigated. We found no increased risk of obesity and no association with BMI at any age with the FTO rs9939609 variant. We found however interaction between physical activity at the age of 50 years and genotype on BMI levels (p = 0.039) and there was a clear trend towards larger BMI differences between the TT and AA carriers as well as between AT and AA carriers in the less physically active subjects.

Conclusion
Here we found that the well established obesity risk allele for a common variant in FTO does not associate with increased BMI levels in a Swedish population of adult men which reached adulthood before the appearance of today's obesogenic enviroment. There is an interaction between physical activity and the effect of the FTO genotype on BMI levels suggesting that lack of physical activity is a requirement for an association of FTO gene variants to obesity.
Association of ADAM33 gene polymorphisms with COPD in a northeastern Chinese population
Authors: Wang Xinyan , Li Lei , Xiao Jinling , Jin Chengzhen , Huang Kun , Kang Xiaowen , Wu Xiaomei , Lv Fuzhen 
Published: December 2009

AbstractBackgroundChronic obstructive pulmonary disease (COPD) is influenced by both environmental and genetic factors. ADAM33 (a disintegrin and metalloproteinase 33) has been one of the most exciting candidate genes for asthma since its first association with the disease in Caucasian populations. Recently, ADAM33 was shown to be associated with excessive decline of lung function and COPD. The aim of this study was to evaluate the potential relationship between polymorphisms of ADAM33 and COPD in a Han population in northeastern China.MethodsA total of 312 COPD patients and a control group of 319 healthy volunteers were recruited for this study. Eight polymorphic loci (V4, T+1, T2, T1, S2, S1, Q-1, and F+1) of ADAM33 were selected for genotyping. Genotypes were determined by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.ResultsStatistically significant differences in the distributions of the T2G, T1G, S2C, and Q-1G alleles between patients and controls were observed (P< 0.001, odds ratio (OR) = 2.81, 95% confidence interval (CI) = 2.19-3.61;P< 0.001, OR = 2.60, 95% CI = 2.06-3.30;P= 0.03, OR = 1.31, 95% CI = 1.02-1.69; andP< 0.001, OR = 1.93, 95% CI = 1.50-2.50, respectively). Haplotype analysis showed that the frequencies of the CGGGGAGC, CGGGGAGT, CGGGCAGC, and CGGGGGGC haplotypes were significantly higher in the case group than in the control group (P= 0.0002, 0.0001, 0.0005, and 0.0074, respectively). In contrast, the haplotype CGAAGAGC was more common in the control group than in the case group (P< 0.0001).ConclusionThese preliminary results suggest an association between ADAM33 polymorphisms and COPD in a Chinese Han population.
Synthesis and expression of CDw75 antigen in human colorectal cancer
Authors: Costa-Nogueira Clotilde , Villar-Portela Susana , Cuevas Elisa , Gil-Martín Emilio , Fernández-Briera Almudena 
Published: December 2009

Abstract

Background
Increased ST6Gal I activity has been associated with the α(2,6)sialylation enhancement of membrane glycoconjugates observed in metastatic colorectal carcinomas (CRC). Siaα(2,6)Galβ(1,4)GlcNAc sequence, known as CDw75, is a sialylated carbohydrate determinant generated by the ST6Gal I. This epitope has been reported to be associated with the progression of gastric and colorectal tumours, hence there are only a few conclusive studies to date.

Methods
By radioisotopic techniques we evaluated the ST6Gal I activity in healthy, transitional and tumour tissues from 43 patients with CRC. By immunohistochemistry we assessed the CDw75 expression in 25 colorectal adenomas, 43 tumours, 13 transitional and 28 healthy tissues of CRC patients.

Results
ST6Gal I activity was likewise found to be statistically higher in tumour tissue respect to healthy tissue from CRC patients. CDw75 expression was positive in 20% of colorectal adenomas. Furthermore, 70% of tumour specimens and 8.3% of transitional specimens were positive for CDw75 expression, whereas none of the healthy ones showed the presence of the epitope.

Conclusion
The major contribution of this study is the inclusion of data from transitional tissue and the analysis of CDw75 antigen expression in CRC and in colorectal adenomas, little known so far. ST6Gal I activity and CDw75 antigen expression were increased in CRC. Although their comparison did not reach the statistical significance, a great extent of patients showed both, an enhanced tumour ST6Gal I activity and an increased CDw75 expression in the tumour tissue. So, these two variables may play a role in malignant transformation. The expression of CDw75 in colorectal adenomas suggests that this antigen may be a tumour marker in CRC.
The effectiveness of health coaching, home blood pressure monitoring, and home-titration in controlling hypertension among low-income patients: protocol for a randomized controlled trial
Authors: Bennett Heather , Laird Kelsey , Margolius David , Ngo Victoria , Thom David H , Bodenheimer Thomas 
Published: December 2009

Abstract

Background
Despite the many antihypertensive medications available, two-thirds of patients with hypertension do not achieve blood pressure control. This is thought to be due to a combination of poor patient education, poor medication adherence, and "clinical inertia." The present trial evaluates an intervention consisting of health coaching, home blood pressure monitoring, and home medication titration as a method to address these three causes of poor hypertension control.

Methods/Design
The randomized controlled trial will include 300 patients with poorly controlled hypertension. Participants will be recruited from a primary care clinic in a teaching hospital that primarily serves low-income populations.
An intervention group of 150 participants will receive health coaching, home blood pressure monitoring, and home-titration of antihypertensive medications during 6 months. The control group (n = 150) will receive health coaching plus home blood pressure monitoring for the same duration. A passive control group will receive usual care. Blood pressure measurements will take place at baseline, and after 6 and 12 months. The primary outcome will be change in systolic blood pressure after 6 and 12 months. Secondary outcomes measured will be change in diastolic blood pressure, adverse events, and patient and provider satisfaction.

Discussion
The present study is designed to assess whether the 3-pronged approach of health coaching, home blood pressure monitoring, and home medication titration can successfully improve blood pressure, and if so, whether this effect persists beyond the period of the intervention.

Trial Registration
ClinicalTrials.gov identifier: NCT01013857
Researching the mental health needs of hard-to-reach groups: managing multiple sources of evidence
Authors: Dowrick Christopher , Gask Linda , Edwards Suzanne , Aseem Saadia , Bower Peter , Burroughs Heather , Catlin Amy , Chew-Graham Carolyn , Clarke Pam , Gabbay Mark , Gowers Simon , Hibbert Derek , Kovandzic Marija , Lamb Jonathan , Lovell Karina , Rogers Anne , Lloyd-Williams Mari , Waheed Waquas ,   the AMP Group
Published: December 2009

Abstract

Background
Common mental health problems impose substantial challenges to patients, carers, and health care systems. A range of interventions have demonstrable efficacy in improving the lives of people experiencing such problems. However many people are disadvantaged, either because they are unable to access primary care, or because access does not lead to adequate help. New methods are needed to understand the problems of access and generate solutions. In this paper we describe our methodological approach to managing multiple and diverse sources of evidence, within a research programme to increase equity of access to high quality mental health services in primary care.

Methods
We began with a scoping review to identify the range and extent of relevant published material, and establish key concepts related to access. We then devised a strategy to collect - in parallel - evidence from six separate sources: a systematic review of published quantitative data on access-related studies; a meta-synthesis of published qualitative data on patient perspectives; dialogues with local stakeholders; a review of grey literature from statutory and voluntary service providers; secondary analysis of patient transcripts from previous qualitative studies; and primary data from interviews with service users and carers.
We synthesised the findings from these diverse sources, made judgements on key emerging issues in relation to needs and services, and proposed a range of potential interventions. These proposals were debated and refined using iterative electronic and focus group consultation procedures involving international experts, local stakeholders and service users.

Conclusions
Our methods break new ground by generating and synthesising multiple sources of evidence, connecting scientific understanding with the perspectives of users, in order to develop innovative ways to meet the mental health needs of under-served groups.
Macromolecular and elemental composition analysis and extracellular metabolite balances of Pichia pastoris growing at different oxygen levels
Authors: Carnicer Marc , Baumann Kristin , Töplitz Isabelle , Sánchez-Ferrando Francesc , Mattanovich Diethard , Ferrer Pau , Albiol Joan 
Published: December 2009

AbstractBackgroundAnalysis of the cell operation at the metabolic level requires collecting data of different types and to determine their confidence level. In addition, the acquired information has to be combined in order to obtain a consistent operational view. In the case ofPichia pastoris, information of its biomass composition at macromolecular and elemental level is scarce particularly when different environmental conditions, such as oxygen availability or, genetic backgrounds (e.g. recombinant protein productionvs. non production conditions) are compared.ResultsP. pastoriscells growing in carbon-limited chemostat cultures under different oxygenation conditions (% O2in the bioreactor inlet gas: 21%, 11% and 8%, corresponding to normoxic, oxygen-limiting and hypoxic conditions, respectively), as well as under recombinant protein (antibody fragment, Fab) producing and non-producing conditions, were analyzed from different points of view. On the one hand, the macromolecular and elemental composition of the biomass was measured using different techniques at the different experimental conditions and proper reconciliation techniques were applied for gross error detection of the measured substrates and products conversion rates. On the other hand, fermentation data was analyzed applying elemental mass balances. This allowed detecting a previously missed by-product secreted under hypoxic conditions, identified as arabinitol (aka. arabitol). After identification of this C5 sugar alcohol as a fermentation by-product, the mass balances of the fermentation experiments were validated.ConclusionsAfter application of a range of analytical and statistical techniques, a consistent view of growth parameters and compositional data ofP. pastoriscells growing under different oxygenation conditions was obtained. The obtained data provides a first view of the effects of oxygen limitation on the physiology of this microorganism, while recombinant Fab production seems to have little or no impact at this level of analysis. Furthermore, the results will be highly useful in other complementary quantitative studies ofP. pastorisphysiology, such as metabolic flux analysis.
Transforming growth factor-beta inhibits aromatase gene transcription in human trophoblast cells via the Smad2 signaling pathway
Authors: Zhou Hong , Fu Guodong , Yu Hui , Peng Chun 
Published: December 2009

Abstract

Background
Transforming growth factor-beta (TGF-beta) is known to exert multiple regulatory functions in the human placenta, including inhibition of estrodial production. We have previously reported that TGF-beta1 decreased aromatase mRNA levels in human trophoblast cells. The objective of this study was to investigate the molecular mechanisms underlying the regulatory effect of TGF-beta1 on aromatase expression.

Methods
To determine if TGF-beta regulates aromatase gene transcription, several reporter constructs containing different lengths of the placental specific promoter of the human aromatase gene were generated. JEG-3 cells were transiently transfected with a promoter construct and treated with or without TGF-beta1. The promoter activity was measured by luciferase assays. To examine the downstream signaling molecule mediating the effect of TGF-beta on aromatase transcription, cells were transiently transfected with dominant negative mutants of TGF-beta type II (TbetaRII) and type I receptor (ALK5) receptors before TGF-beta treatment. Smad2 activation was assessed by measuring phophorylated Smad2 protein levels in cytosolic and nuclear fractions. Smad2 expression was silenced using a siRNA expression construct. Finally, aromatase mRNA half-life was determined by treating cells with actinomycin D together with TGF-beta1 and measuring aromatase mRNA levels at various time points after treatment.

Results and Discussion
TGF-beta1 inhibited the aromatase promoter activity in a time- and dose-dependent manner. Deletion analysis suggests that the TGF-β1 response element resides between -422 and -117 nucleotides upstream from the transcription start site where a Smad binding element was found. The inhibitory effect of TGF-beta1 was blocked by dominant negative mutants of TbetaRII and ALK5. TGF-beta1 treatment induced Smad2 phosphorylation and translocation into the nucleus. On the other hand, knockdown of Smad2 expression reversed the inhibitory effect of TGF-beta1 on aroamtase transcription. Furthermore, TGF-beta1 accelerated the degradation of aromatase mRNA.

Conclusion
Our results demonstrate that TGF-beta1 exerts regulatory effects on aromatase gene at both transcriptional and post-transcriptional levels. The transcriptional regulation of aromatase gene by TGF-beta1 is mediated by the canonical TGF-beta pathway involving TbetaRII, ALK5 and Smad2. These findings further support the role of TGF-beta1 in regulating human placental functions and pregnancy.
Seven mistakes and potential solutions in epidemiology, including a call for a World Council of Epidemiology and Causality
Authors: Bhopal Raj 
Published: December 2009

AbstractAll sciences make mistakes, and epidemiology is no exception. I have chosen 7 illustrative mistakes and derived 7 solutions to avoid them. The mistakes (Roman numerals denoting solutions) are:

Failing to provide the context and definitions of study populations. (I Describe the study population in detail)

Insufficient attention to evaluation of error. (II Don't pretend error does not exist.)

Not demonstrating comparisons are like-for-like. (III Start with detailed comparisons of groups.)

Either overstatement or understatement of the case for causality. (IV Never say this design cannot contribute to causality or imply causality is ensured by your design.)

Not providing both absolute and relative summary measures. (V Give numbers, rates and comparative measures, and adjust summary measures such as odds ratios appropriately.)

In intervention studies not demonstrating general health benefits. (VI Ensure general benefits (mortality/morbidity) before recommending application of cause-specific findings.)

Failure to utilise study data to benefit populations. (VII Establish a World Council on Epidemiology to help infer causality from associations and apply the work internationally.)

Analysis of these and other common mistakes is needed to benefit from the increasing discovery of associations that will be multiplying as data mining, linkage, and large-scale scale epidemiology become commonplace.
The effects of HIF-1alpha on gene expression profiles of NCI-H446 human small cell lung cancer cells
Authors: Wan Jun , Ma Jinben , Mei Ju , Shan Genfa 
Published: December 2009

Abstract

Background
Gene targeted therapy refers to any therapy focused on one of the many biological features of the tumor. Such features are mediated by specific genes that are involved in tumor metastasis, recurrence, poor response to chemotherapy and others. Hypoxia is an important pathognomonic feature of many malignant tumors including SCLC (small cell lung cancer). HIF-1alpha, which is induced by hypoxia, is the most important regulatory factor of many specific genes that can influence the biological features of tumors.

Methods
In this study, we tried to elucidate the changes in gene expression profiles of SCLC NCI-H446 cells mediated by HIF-1alpha. According to different treatments of cells, three experimental pairwise comparisons were designed: hypoxia group vs. control group, Ad5-HIF-1alpha group vs. Ad5 group, and Ad5-siHIF-1 alpha group Vs Ad5 group.

Results
Results from the analysis of gene expression profiles indicated that there were 65 genes upregulated and 28 genes downregulated more than two-fold in all three experimental pairwise comparisons. These genes were involved in transport, signal-transduction, cell adhesion/motility, growth factor/cytokines, transcription, inflammatory response, metabolic process, in addition to others. SOCS1, IGFBP5, IL-6 and STAT3 were also upregulated at protein level. SOCS1 could significantly induce apoptosis and suppress growth of NCI-H446 cells but HIF-1alpha could induce growth and suppress apoptosis.

Conclusions
Through this research, we are trying to find novel functional genes that are mediated by HIF-1alpha and provide the theoretical basis for new therapeutic targets. HIF-1 alpha maybe upregulate the expression of SOCS1 through mediation of STAT3 and IL-6. In addition, SOCS1 could significantly induce apoptosis and suppress growth of NCI-H446 cells. This was contrary to HIF-1alpha and it indicated that there might be an antagonism effect between HIF-1alpha and SOCS1 on regulating growth and apoptosis of NCI-H446 cells.
Acute interstitial nephritis during rifampicin therapy can be a paradoxical response: a case report
Authors: van der Meulen Jan , de Jong Gijs MT , Westenend Pieter J 
Published: December 2009

Abstract
An 18-year-old Ethiopian woman presented with debilitating back pain and high fever. X-ray examinations showed diffuse pulmonary tuberculosis and a psoas abscess. After starting rifampicin, isoniazid, ethambutol and pyrazinamide, acute interstitial nephritis developed that spontaneously recovered. According to Harrison's Online rifampicin should have been causative, but the spontaneous recovery excluded that possibility. The clinical course fit the diagnosis of a paradoxical response, for which recently risk factors have been described. Thus, a paradoxical response should be added to the list of causes of interstitial nephritis in tuberculosis patients and in such cases rifampicin could be continued.
Normalization of systemic arterial hypertension following removal of posterior fossa hemangioblastoma: a case report
Authors: Saberi Hooshang , Meybodi Ali Tayebi , Zeinalizadeh Mehdi 
Published: December 2009

Abstract
The concept of compression of the rostral ventrolateral medulla as a cause for hypertension is gaining more and more interest. This report is about a 36-year-old male with a three years history of hypertension who presented with a posterior fossa mass suggestive of a hemangioblastoma. Laboratory and imaging studies ruled out the presence of von Hippel-Lindau disease and/or concomitant pheochromocytoma. Post-surgical blood pressure monitoring revealed a 40 mmHg decline in blood pressure. It could be hypothesized that alleviation the compressive effect of the tumour on the rostral ventrolateral medulla as proposed by previous studies could be a contributing factor.
Recessive congenital myotonia resulting from maternal isodisomy of chromosome 7: a case report
Authors: Bulli Cristina , Battistella Pier Antonio , Bordignon Marta , Bramanti Placido , Novelli Giuseppe , Sangiuolo Federica 
Published: December 2009

Abstract
Autosomal dominant (Thomsen) and recessive (Becker) congenital myotonia are two different non dystrophic disorders, due to allelic mutations of the muscle chloride channel gene, located on chromosome 7q35. More than two thirds of the muscle chloride channel gene mutations occur independently in unique families and cause the recessive form of the disease. Becker disease is more common and severe than Thomsen disease. Here, we report on the clinical and molecular data of the first patient with maternal uniparental disomy for chromosome 7 and recessive congenital myotonia. The proband is a 15-year-old male, homozygous for a missense mutation within muscle chloride channel gene, showing few characteristic signs of the Silver Russell Syndrome.
Resistance exercise training lowers HbA1c more than aerobic training in adults with type 2 diabetes
Authors: Bweir Salameh , Al-Jarrah Muhammed , Almalty Abdul-Majeed , Maayah Mikhled , Smirnova Irina V , Novikova Lesya , Stehno-Bittel Lisa 
Published: December 2009

Abstract

Background
The aim of this study was to compare the effects of 10 weeks of resistance or treadmill exercises on glycemic indices levels prior to and immediately following exercise in adults with type 2 diabetes.

Research Design and Method
Twenty inactive subjects (mean age 53.5 years) with type 2 diabetes enrolled in the study. Baseline HbA1c, blood glucose levels, heart rate, and blood pressure were measured for each subject prior to the initiation of the exercise program. Subsequently, subjects were matched to age, waist circumference and sex and assigned to either isocaloric resistance or treadmill exercise groups, which met 3 times per week for 10 weeks.

Results
Both groups showed a reduction in pre and post-exercise blood glucose and HbA1c values. There was no change in resting blood pressure or heart rate in either group during the course of the 10 week intervention. The group receiving resistance exercises showed significant differences in the daily pre-exercise plasma glucose readings between the beginning and end of the exercise protocol (p < 0.001). There were significant improvements in the mean HbA1c reading pre and post training in both groups (p < 0.001). However, the greater reduction was noted in the resistance exercise group, and at 10 weeks their HbA1c levels were significantly lower than the group that received treadmill exercises (p < 0.006).

Conclusion
Ten weeks of resistance exercises were associated with a significantly better glycemic control in adults with type 2 diabetes compared to treadmill exercise.