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1.
Background
Cerebral cavernous malformations (CCM) present as either sporadic or autosomal dominant conditions with incomplete penetrance of symptoms. Differences in genetic and environmental factors might be minimized among first-degree relatives. We therefore studied clinical expression in a family with several affected members.Methods
We studied a three-generation family with the onset of CCM as a cerebral haemorrhage in the younger (four-year-old) sibling. Identification and enumeration of CCMs were performed in T2-weighted or gradient-echo MRIs of the whole brains. Genetic analysis comprised SCCP, sequencing and restriction polymorphism of the Krit1 gene in the proband and at risk relatives.Results
The phenotypes of cerebral cavernous malformations (CCMs) in carriers of Krit1 mutations were very variable. We identified a novel frameshift mutation caused by a 1902A insertion in exon 17 of the Krit1 gene, which leads to a premature TAA triplet and predicts the truncating phenotype Y634X. A very striking finding was the absence of both clinical symptoms and CCMs in the eldest sibling harbouring the 1902insA.Conclusions
Patients in this family, harbouring the same mutation, illustrate the very variable clinical and radiological expression of a Krit1 mutation. The early and critical onset in the proband contrasts with minor clinical findings in affected relatives. This consideration is important in genetic counselling.2.
Yayoi Nishida Yasuo Takahashi Tomohiro Nakayama Masayoshi Soma Noboru Kitamura Satoshi Asai 《Cardiovascular diabetology》2010,9(1):38
Background
Studies focusing on the add-on effects of angiotensin II type 1 receptor blockers (ARBs) other than their antihypertensive effect are receiving attention. However, the effects of prolonged administration of ARBs on lipid metabolism in clinical cases are unclear. Our aims were to survey the changes in plasma lipid profile in patients with hypertension over a one-year period, and to examine the correlations between these values and the time after the start of ARB monotherapy with candesartan.Methods
We carried out candesartan monotherapy in patients with mild to moderate hypertension and examined the longitudinal changes in plasma lipid profile. Data from 405 patients for triglyceride (TG), 440 for total cholesterol (TC), 313 for high density lipoprotein cholesterol (HDL-C) and 304 for low density lipoprotein cholesterol (LDL-C) were obtained from the electronic medical records (EMRs) in the Clinical Data Warehouse (CDW) of Nihon University School of Medicine (NUSM). The inverse probability of treatment weighting (IPTW) method (calculated from the inverse of the propensity score) was used to balance the covariates and reduce bias in each treatment duration. Linear mixed effects models were used to analyse the relationship between these longitudinal data of blood examinations and covariates of patient sex, age, diagnosis of diabetes mellitus (DM) and duration of candesartan monotherapy.Results
Plasma HDL-C level was associated with sex, duration of treatment, and interaction of sex and treatment duration, but not with age or diagnosis of DM. HDL-C level was significantly decreased during the 6~9 months period (p = 0.0218) compared with baseline. TG and TC levels were associated with sex, but not with age, diagnosis of DM or treatment duration. LDL-C level was not associated with any covariate. Analysis of the subjects divided by sex revealed a decrease in HDL-C in female subjects (during the 6~9 months period: p = 0.0054), but not in male subjects.Conclusions
Our study revealed that administration of candesartan slightly decreased HDL-C in female subjects. However, TG, TC and LDL-C levels were not influenced by candesartan monotherapy. Candesartan may be safely used for patients with hypertension with respect to lipid metabolism, because the effect of candesartan on lipids may be small.3.
Jamie V. de Seymour Stephanie Tu Xiaoling He Hua Zhang Ting-Li Han Philip N. Baker Karolina Sulek 《Metabolomics : Official journal of the Metabolomic Society》2018,14(6):79
Introduction
Intrahepatic cholestasis of pregnancy (ICP) is a common maternal liver disease; development can result in devastating consequences, including sudden fetal death and stillbirth. Currently, recognition of ICP only occurs following onset of clinical symptoms.Objective
Investigate the maternal hair metabolome for predictive biomarkers of ICP.Methods
The maternal hair metabolome (gestational age of sampling between 17 and 41 weeks) of 38 Chinese women with ICP and 46 pregnant controls was analysed using gas chromatography–mass spectrometry.Results
Of 105 metabolites detected in hair, none were significantly associated with ICP.Conclusion
Hair samples represent accumulative environmental exposure over time. Samples collected at the onset of ICP did not reveal any metabolic shifts, suggesting rapid development of the disease.4.
Background
Identification of phosphorylation sites by computational methods is becoming increasingly important because it reduces labor-intensive and costly experiments and can improve our understanding of the common properties and underlying mechanisms of protein phosphorylation.Methods
A multitask learning framework for learning four kinase families simultaneously, instead of studying each kinase family of phosphorylation sites separately, is presented in the study. The framework includes two multitask classification methods: the Multi-Task Least Squares Support Vector Machines (MTLS-SVMs) and the Multi-Task Feature Selection (MT-Feat3).Results
Using the multitask learning framework, we successfully identify 18 common features shared by four kinase families of phosphorylation sites. The reliability of selected features is demonstrated by the consistent performance in two multi-task learning methods.Conclusions
The selected features can be used to build efficient multitask classifiers with good performance, suggesting they are important to protein phosphorylation across 4 kinase families.5.
Xiaowei Wang Mingjie Wang Shuangshuang Shao Yang Zhang Siyu Liu Yue Gao Yuhang Shen Pinghui Sun 《BMC endocrine disorders》2018,18(1):89
Background
To explore the risk factors of coexisting prediabetes and prehypertension, to provide theoretical basis for early intervention.Methods
A multi-stage stratified random cluster sampling method was used to randomly select adult residents from Jilin Province in 2013 for questionnaire surveys, physical examinations, and laboratory tests.Results
The prevalence of coexisting prediabetes and prehypertension in Jilin Province was 11.3%. The binary Logistic regression results showed that age, sex, education, triglyceride (TG), BMI, waist circumference and alcohol consumption were the effects of factor coexisting prediabetes and prehypertension.Conclusion
It is important to pay attention to the early stage of hypertension and diabetes, control the transition from prehypertension and prediabetes to hypertension and diabetes, and improve the health of residents.6.
Background
Infant feeding is governed by environmental as well as cultural factors. Breastfeeding knowledge and attitudes are known to be associated with breastfeeding duration. This study investigated breastfeeding information, attitudes and supplementary feeding in the central hills district of Nepal.Methods
A community-based prospective cohort study of 701 pregnant women was conducted. Information on breastfeeding attitudes, feeding practices and supplementary feeding was sought from the cohort at 4 weeks, 12 weeks and 22 weeks postpartum through repeated interviews using validated questionnaires.Results
Average duration of intended breastfeeding was 28 months (SD 7.9) and average target time to introduce solid foods was 6.1 months (SD 1.2). About 80% of women reported their husband, mother/mother-in-law preferred breastfeeding. Eleven percent of the cohort said that breastfeeding was not enjoyable. At 12 weeks and 22 weeks after birth, about a quarter (24.8%) and half (52.8%) of the infants were introduced cow/buffalo milk, respectively, while only 6.3% and 13.4% of them were given infant formula. Overall, any breastfeeding rate remained high at over 98% throughout the follow up period.Conclusions
Breastfeeding attitudes were encouraging in this population. Breastfeeding was almost universal. Use of infant formula was quite low, whereas cow or buffalo milk appeared to be popular supplementary foods.7.
Sophie Hellstrand Ulrika Ericson Christina-Alexandra Schulz Isabel Drake Bo Gullberg Bo Hedblad Gunnar Engström Marju Orho-Melander Emily Sonestedt 《Genes & nutrition》2016,11(1):20
Background
By taking diet quality into account, we may clarify the relationship between genetically elevated triglycerides (TG) and low-density lipoprotein-cholesterol (LDL-C), and better understand the inconsistent results regarding genetically elevated high-density lipoprotein-cholesterol (HDL-C), and cardiovascular disease (CVD) risk.Methods
We included 24,799 participants (62 % women, age 44–74 years) from the Malmö Diet and Cancer cohort. During a mean follow-up time of 15 years, 3068 incident CVD cases (1814 coronary and 1254 ischemic stroke) were identified. Genetic risk scores (GRSs) were constructed by combining 80 validated genetic variants associated with higher TG and LDL-C or lower HDL-C. The participants’ dietary intake, assessed by a modified diet history method, was ranked according to a diet quality index that included six dietary components: saturated fat, polyunsaturated fat, fish, fiber, fruit and vegetables, and sucrose.Results
The GRSLDL-C (P?=?5?×?10?6) and GRSHDL-C (P?=?0.02) but not GRSTG (P?=?0.08) were significantly associated with CVD risk. No significant interaction between the GRSs and diet quality was observed on CVD risk (P?>?0.39). A high compared to a low diet quality attenuated the association between GRSLDL-C and the risk of incident ischemic stroke (P interaction?=?0.01).Conclusion
We found some evidence of an interaction between diet quality and GRSLDL-C on ischemic stroke.8.
N. Cesbron A.-L. Royer Y. Guitton A. Sydor B. Le Bizec G. Dervilly-Pinel 《Metabolomics : Official journal of the Metabolomic Society》2017,13(8):99
Introduction
Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.Objectives
In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.Methods
The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.Results
A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.Conclusion
The workflow generated repeatable and informative fingerprints for robust metabolome characterization.9.
Anna Skorczyk-Werner Anna Wawrocka Natalia Kochalska Maciej Robert Krawczynski 《Orphanet journal of rare diseases》2018,13(1):221
Background
Choroideremia (CHM) is a rare X-linked recessive retinal dystrophy characterized by progressive chorioretinal degeneration in the males affected. The symptoms include night blindness in childhood, progressive peripheral vision loss and total blindness in the late stages. The disease is caused by mutations in the CHM gene encoding Rab Escort Protein 1 (REP-1). The aim of the study was to identify the molecular basis of choroideremia in five families of Polish origin.Methods
Six male patients from five unrelated families of Polish ethnicity, who were clinically diagnosed with choroideremia, were examined in this study. An ophthalmologic examination performed in all the probands included: best-corrected visual acuity, slit-lamp examination, funduscopy, fluorescein angiography and perimetry. The entire coding region encompassing 15 exons and the flanking intronic sequences of the CHM gene were amplified with PCR and directly sequenced in all the patients.Results
Five variants in the CHM gene were identified in the five families examined. Two of the variants were new: c.1175dupT and c.83C?>?G, while three had been previously reported.Conclusions
This study provides the first molecular genetic characteristics of patients with choroideremia from the previously unexplored Polish population.10.
Jochen Profit Katri V Typpo Sylvia J Hysong LeChauncy D Woodard Michael A Kallen Laura A Petersen 《Implementation science : IS》2010,5(1):13
Background
The measurement of healthcare provider performance is becoming more widespread. Physicians have been guarded about performance measurement, in part because the methodology for comparative measurement of care quality is underdeveloped. Comprehensive quality improvement will require comprehensive measurement, implying the aggregation of multiple quality metrics into composite indicators.Objective
To present a conceptual framework to develop comprehensive, robust, and transparent composite indicators of pediatric care quality, and to highlight aspects specific to quality measurement in children.Methods
We reviewed the scientific literature on composite indicator development, health systems, and quality measurement in the pediatric healthcare setting. Frameworks were selected for explicitness and applicability to a hospital-based measurement system.Results
We synthesized various frameworks into a comprehensive model for the development of composite indicators of quality of care. Among its key premises, the model proposes identifying structural, process, and outcome metrics for each of the Institute of Medicine's six domains of quality (safety, effectiveness, efficiency, patient-centeredness, timeliness, and equity) and presents a step-by-step framework for embedding the quality of care measurement model into composite indicator development.Conclusions
The framework presented offers researchers an explicit path to composite indicator development. Without a scientifically robust and comprehensive approach to measurement of the quality of healthcare, performance measurement will ultimately fail to achieve its quality improvement goals.11.
Dimitrios J. Floros Paul R. Jensen Pieter C. Dorrestein Nobuhiro Koyama 《Metabolomics : Official journal of the Metabolomic Society》2016,12(9):145
Introduction
Natural products from culture collections have enormous impact in advancing discovery programs for metabolites of biotechnological importance. These discovery efforts rely on the metabolomic characterization of strain collections.Objective
Many emerging approaches compare metabolomic profiles of such collections, but few enable the analysis and prioritization of thousands of samples from diverse organisms while delivering chemistry specific read outs.Method
In this work we utilize untargeted LC–MS/MS based metabolomics together with molecular networking to inventory the chemistries associated with 1000 marine microorganisms.Result
This approach annotated 76 molecular families (a spectral match rate of 28 %), including clinically and biotechnologically important molecules such as valinomycin, actinomycin D, and desferrioxamine E. Targeting a molecular family produced primarily by one microorganism led to the isolation and structure elucidation of two new molecules designated maridric acids A and B.Conclusion
Molecular networking guided exploration of large culture collections allows for rapid dereplication of know molecules and can highlight producers of uniques metabolites. These methods, together with large culture collections and growing databases, allow for data driven strain prioritization with a focus on novel chemistries.12.
Rachel A. Spicer Christoph Steinbeck 《Metabolomics : Official journal of the Metabolomic Society》2018,14(1):16
Introduction
Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.Objectives
(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.Methods
A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.Results
Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.Conclusion
Further efforts are required to improve data sharing in metabolomics.13.
14.
Introduction
Untargeted metabolomics is a powerful tool for biological discoveries. To analyze the complex raw data, significant advances in computational approaches have been made, yet it is not clear how exhaustive and reliable the data analysis results are.Objectives
Assessment of the quality of raw data processing in untargeted metabolomics.Methods
Five published untargeted metabolomics studies, were reanalyzed.Results
Omissions of at least 50 relevant compounds from the original results as well as examples of representative mistakes were reported for each study.Conclusion
Incomplete raw data processing shows unexplored potential of current and legacy data.15.
Nadine Strehmel David Strunk Veronika Strehmel 《Metabolomics : Official journal of the Metabolomic Society》2017,13(11):135
Introduction
Aqueous–methanol mixtures have successfully been applied to extract a broad range of metabolites from plant tissue. However, a certain amount of material remains insoluble.Objectives
To enlarge the metabolic compendium, two ionic liquids were selected to extract the methanol insoluble part of trunk from Betula pendula.Methods
The extracted compounds were analyzed by LC/MS and GC/MS.Results
The results show that 1-butyl-3-methylimidazolium acetate (IL-Ac) predominantly resulted in fatty acids, whereas 1-ethyl-3-methylimidazolium tosylate (IL-Tos) mostly yielded phenolic structures. Interestingly, bark yielded more ionic liquid soluble metabolites compared to interior wood.Conclusion
From this one can conclude that the application of ionic liquids may expand the metabolic snapshot.16.
Renato de Souza Pinto Lemgruber Kaspar Valgepea Mark P. Hodson Ryan Tappel Sean D. Simpson Michael Köpke Lars K. Nielsen Esteban Marcellin 《Metabolomics : Official journal of the Metabolomic Society》2018,14(3):35
Introduction
Quantification of tetrahydrofolates (THFs), important metabolites in the Wood–Ljungdahl pathway (WLP) of acetogens, is challenging given their sensitivity to oxygen.Objective
To develop a simple anaerobic protocol to enable reliable THFs quantification from bioreactors.Methods
Anaerobic cultures were mixed with anaerobic acetonitrile for extraction. Targeted LC–MS/MS was used for quantification.Results
Tetrahydrofolates can only be quantified if sampled anaerobically. THF levels showed a strong correlation to acetyl-CoA, the end product of the WLP.Conclusion
Our method is useful for relative quantification of THFs across different growth conditions. Absolute quantification of THFs requires the use of labelled standards.17.
Rui-Feng Yang Hanlei Zhang Zhongchun Wang Xiao-Yong Liu Zhi Lin 《Immunity & ageing : I & A》2018,15(1):14
Background
Abdominal obesity is an independent risk factor for coronary heart disease (CHD) and high serum triglyceride (TG) and free fatty acid levels may precipitate or aggravate CHD.Methods
We enrolled patients with coronary heart disease in our hospital from October 2008 to July 2009. Patients with high TG and increased WC, i.e. waist phenotype WP were included in group A. In group B, were included patients with high TG but not WP. Group C consisted of patients with WP but not high TG. Finally, Group D was composed of patients without high TG or WP. Serum FFA levels for all patients were measured by ELISA. The relationship between TG levels, WC, FFA levels, and coronary artery score was analysed by a single variable regression.Results
Group A had a significantly higher FFA level than the other groups. Regression analysis showed that FFA, TG, WC, hip circumference, waist-to-height ratio, systolic blood pressure, pulse pressure index, and low-density lipoprotein cholesterol all positively correlated with CAS (r?=?0.160 ~?0.415, P?=?0.000 ~?0.032). After we controlled for traditional risk factors for cardiovascular disease, FFA levels remained positively correlated to the CAS (r?=?0.365, P?<?0.001).Conclusion
The serum FFA level for patients with complications of both increased WC and high TG levels was significantly higher than that of patients without either of these complications. The close correlation between the CAS and FFA levels showed by regression analysis suggested that inflammation in these patients was more serious. Increased WC and high TG levels as well as FFA level are valuable for the prediction of cardiovascular disease and can be applied as a clinical guidance for early intervention in the treatment of coronary heart diseases.18.
Background
In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.Methods
The physical basis of these intuitive maps is clarified by means of analytically solvable problems.Results
Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.Conclusion
Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.19.
Thijs Welle Anna T. Hoekstra Ineke A. J. J. M. Daemen Celia R. Berkers Matheus O. Costa 《Metabolomics : Official journal of the Metabolomic Society》2017,13(7):83
Introduction
Swine dysentery caused by Brachyspira hyodysenteriae is a production limiting disease in pig farming. Currently antimicrobial therapy is the only treatment and control method available.Objective
The aim of this study was to characterize the metabolic response of porcine colon explants to infection by B. hyodysenteriae.Methods
Porcine colon explants exposed to B. hyodysenteriae were analyzed for histopathological, metabolic and pro-inflammatory gene expression changes.Results
Significant epithelial necrosis, increased levels of l-citrulline and IL-1α were observed on explants infected with B. hyodysenteriae.Conclusions
The spirochete induces necrosis in vitro likely through an inflammatory process mediated by IL-1α and NO.20.
Leonie Venter Du Toit Loots Lodewyk Japie Mienie Peet J. Jansen van Rensburg Shayne Mason Andre Vosloo Jeremie Zander Lindeque 《Metabolomics : Official journal of the Metabolomic Society》2018,14(4):49