A dosing algorithm including genetic (VKORC1 and CYP2C9 genotypes) and nongenetic factors (age, weight, therapeutic indication, and cotreatment with amiodarone or simvastatin) explained 51% of the ...variance in stable weekly warfarin doses in 390 patients attending an anticoagulant clinic in a Brazilian public hospital. The VKORC1 3673G>A genotype was the most important predictor of warfarin dose, with a partial R2 value of 23.9%. Replacing the VKORC1 3673G>A genotype with VKORC1 diplotype did not increase the algorithm's predictive power. We suggest that three other single‐nucleotide polymorphisms (SNPs) (5808T>G, 6853G>C, and 9041G>A) that are in strong linkage disequilibrium (LD) with 3673G>A would be equally good predictors of the warfarin dose requirement. The algorithm's predictive power was similar across the self‐identified “race/color” subsets. “Race/color” was not associated with stable warfarin dose in the multiple regression model, although the required warfarin dose was significantly lower (P = 0.006) in white (29 ± 13 mg/week, n = 196) than in black patients (35 ± 15 mg/week, n = 76).
Clinical Pharmacology & Therapeutics (2008); 84, 6, 722–728 doi:10.1038/clpt.2008.166
This paper describes the experiences using remote laboratories for education and research in the field of Control Engineering. The use of remote laboratories for education in subjects of control is ...increasingly becoming a resorted method by the universities in order to offer a flexible service in schedules with greater and better operation of available resources. Nevertheless, for research activities, remote laboratories are not widely used. The aim of this contribution is thereby to apply the experience of remote laboratories in research applications in order to share complex equipments among different researchers. Some experiments are carried out to demonstrate the effectiveness of using remote laboratories in research experiments related to robotic system. The results of the implementation of remote experimentations to control a 3-DOF parallel robot by using Distance Laboratory System (SLD) are exposed. The performance of the system is evaluated by the possibilities and functionality of the proposed remote laboratory platform.
Introduction
Delirium affects a significant proportion of hospitalized older patients with acute infections. There is growing evidence that delirium accelerates the cognitive decline at long term.
...Objectives
We aimed to determine if delirium during hospitalization was independently associated with cognitive deterioration at one-year.
Methods
From a total of 22 patients (12 C, 4 Dem, 2 D, and 4 DD) delirium (D and DD groups) was associated with a worse score in MOCA of 3-points (p<.02) and 2.5-points (p<.03), respectively, at one year, follow up. Dementia patients without delirium had a decrease of 2-point (p=.04) while cognitively healthy patients had a decrease in 1.08 points (p=.05) (Graph1). MOCA and NPI scores during hospitalization correlated significantly with cognitive decline in the four groups (r=.658, p<.01 and r=.439, p=.02, respectively.)
Results
From a total of 22 patients (12 C, 4 Dem, 2 D and 4 DD) delirium (D and DD groups) was associated with a worse score in MOCA of 3-points (p<.02) and 2.5-points (p<.03), respectively, at one year follow up. Dementia patients without delirium had a of 2-point (p=.04) while cognitively healthy patients had a decrease in 1.08 points (p=.05) (Graph1). MOCA and NPI scores during hospitalization correlated significantly with cognitive decline in the four groups (r=.658, p<.01 and r=.439, p=.02, respectively.)
Conclusions
Individuals developing delirium while recovering from infection have higher rates of cognitive decline after one year, but the cognitive decline is also present to a lower extent for individuals with infections that did not develop delirium.
Disclosure
No significant relationships.
The colonial ascidian Didemnum vexillum, sea carpet squirt, is not only a key marine organism to study morphological ancestral patterns of chordates evolution but it is also of great ecological ...importance due to its status as a major invasive species. Non-coding RNAs, in particular microRNAs (miRNAs), are important regulatory genes that impact development and environmental adaptation. Beyond miRNAs, not much in known about tunicate ncRNAs.
We provide here a comprehensive homology-based annotation of non-coding RNAs in the recently sequenced genome of D. vexillum. To this end we employed a combination of several computational approaches, including blast searches with a wide range of parameters, and secondary structured centered survey with infernal. The resulting candidate set was curated extensively to produce a high-quality ncRNA annotation of the first draft of the D. vexillum genome. It comprises 57 miRNA families, 4 families of ribosomal RNAs, 22 isoacceptor classes of tRNAs (of which more than 72 % of loci are pseudogenes), 13 snRNAs, 12 snoRNAs, and 1 other RNA family. Additionally, 21 families of mitochondrial tRNAs and 2 of mitochondrial ribosomal RNAs and 1 long non-coding RNA.
The comprehensive annotation of the D. vexillum non-coding RNAs provides a starting point towards a better understanding of the restructuring of the small RNA system in ascidians. Furthermore it provides a valuable research for efforts to establish detailed non-coding RNA annotations for other recently published and recently sequences in tunicate genomes.
Transfer RNAs (tRNAs) are ubiquitous in all living organism. They implement the genetic code so that most genomes contain distinct tRNAs for almost all 61 codons. They behave similar to mobile ...elements and proliferate in genomes spawning both local and non-local copies. Most tRNA families are therefore typically present as multicopy genes. The members of the individual tRNA families evolve under concerted or rapid birth-death evolution, so that paralogous copies maintain almost identical sequences over long evolutionary time-scales. To a good approximation these are functionally equivalent. Individual tRNA copies thus are evolutionary unstable and easily turn into pseudogenes and disappear. This leads to a rapid turnover of tRNAs and often large differences in the tRNA complements of closely related species. Since tRNA paralogs are not distinguished by sequence, common methods cannot not be used to establish orthology between tRNA genes.
In this contribution we introduce a general framework to distinguish orthologs and paralogs in gene families that are subject to concerted evolution. It is based on the use of uniquely aligned adjacent sequence elements as anchors to establish syntenic conservation of sequence intervals. In practice, anchors and intervals can be extracted from genome-wide multiple sequence alignments. Syntenic clusters of concertedly evolving genes of different families can then be subdivided by list alignments, leading to usually small clusters of candidate co-orthologs. On the basis of recent advances in phylogenetic combinatorics, these candidate clusters can be further processed by cograph editing to recover their duplication histories. We developed a workflow that can be conceptualized as stepwise refinement of a graph of homologous genes. We apply this analysis strategy with different types of synteny anchors to investigate the evolution of tRNAs in primates and fruit flies. We identified a large number of tRNA remolding events concentrated at the tips of the phylogeny. With one notable exception all phylogenetically old tRNA remoldings do not change the isoacceptor class.
Gene families evolving under concerted evolution are not amenable to classical phylogenetic analyses since paralogs maintain identical, species-specific sequences, precluding the estimation of correct gene trees from sequence differences. This leaves conservation of syntenic arrangements with respect to "anchor elements" that are not subject to concerted evolution as the only viable source of phylogenetic information. We have demonstrated here that a purely synteny-based analysis of tRNA gene histories is indeed feasible. Although the choice of synteny anchors influences the resolution in particular when tight gene clusters are present, and the quality of sequence alignments, genome assemblies, and genome rearrangements limits the scope of the analysis, largely coherent results can be obtained for tRNAs. In particular, we conclude that a large fraction of the tRNAs are recent copies. This proliferation is compensated by rapid pseudogenization as exemplified by many very recent alloacceptor remoldings.
Highlights ► Three genes display altered transcription and chromatin status in the 3xTg-AD model. ► Similar chromatin modulation of BACE1 was found in blood cells of AD patients. ► Increased ...chromatin compaction on the BACE1 promoter was found in MCI patients. ► This work paves the way for further studies on epigenetic biomarkers in AD.
The Montreal Cognitive Assessment (MoCA) is a brief cognitive instrument for screening milder forms of cognitive impairment. The present study aimed to analyze the influence of sociodemographic (age, ...gender, educational level, marital and employment status, geographic region, geographic localization, and residence area) and health variables (subjective memory complaints of the participant and evaluated by the informant, depressive symptoms, and family history of dementia) on the participants' performance on the MoCA. The investigation was carried out in a Portuguese community-based sample of 650 cognitively healthy adults, who were representative of the distribution observed in the Portuguese population. Educational level and age significantly contributed to the prediction of the MoCA scores, explaining 49% of the variance. Regarding health variables, only the subjective memory complaints of the participant showed a small contribution (9%) to the variance on the MoCA scores. This study contributes a useful approach to understanding MoCA performance, stressing the great impact of education and age on scores.
Chronic hepatitis C is one of the main causes of cirrhosis of the liver. Treatment with direct-acting antivirals (DAAs) improves survival. There is controversy as to whether AADs create an increased ...risk for the development of hepatocellular carcinoma (HCC). The aim of the present study was to determine the risk factors for developing HCC in patients with chronic hepatitis C treated with DAAs.
A cohort study was conducted, within the time frame of June 2017 and June 2018, on patients >18 years of age, with chronic hepatitis C, genotypes 1 and 4, with one year of follow-up, to evaluate the presence of HCC.
We analyzed 108 patients, 71 (65%) of whom were women. Mean patient age was 56.24 years (±10.6), 1b was the most frequent genotype (63%), and 49% of the patients received treatment with DAAs (ombitasvir/paritaprevir/ritonavir plus dasabuvir). Thirty-four (31%) patients were obese. Fifty-three percent (58) had cirrhosis and 82% (89) had Child-Pugh class A liver function. Sustained virologic response at 12 weeks was 100%. Eight (7%) patients developed HCC and 1b was the most frequently associated genotype (87%). The presence of regenerative nodules >10 mm (P < .05), esophageal varices (P < .05), cirrhosis of the liver (P < .05), Child-Pugh B-C (P < .05), and alpha-fetoprotein >20 IU/mL (P = 0.20) one year after treatment were associated with the development of HCC.
The risk factors for developing HCC were the presence of cirrhosis of the liver, Child-Pugh class B liver function, esophageal and/or gastric varices, and genotype 1b.
La hepatitis C crónica es de las principales causas de cirrosis hepática. El tratamiento con antivirales de acción directa (AAD) mejora la supervivencia. Existe controversia si los AAD generan un incremento del riesgo para desarrollar carcinoma hepatocelular (CHC). El objetivo del trabajo es determinar los factores de riesgo para desarrollar CHC en pacientes con hepatitis C crónica tratados con AAD.
Estudio de cohorte realizado de junio de 2017 a junio de 2018, incluyó a pacientes >18 años con hepatitis C crónica, genotipo 1 y 4, tratados con AAD, con un año de seguimiento para evaluar la presencia de CHC.
Analizamos 108 pacientes, 71 mujeres (65%), edad media de 56.24 años (±10.6), el genotipo más frecuente 1b (63%), el 49% recibió tratamiento con (ombitasvir, paritaprevir, ritonavir, dasabuvir). Treinta y cuatro pacientes (31%) tenían obesidad. El 53% tenía cirrosis (58) y el 82% en Child-Pugh A (89). La respuesta viral sostenida a las 12 semanas fue del 100%. Ocho pacientes (7%) desarrollaron CHC y el genotipo más asociado fue 1b (87%). La presencia de nódulos de regeneración >10 mm (p < 0.05), várices esofágicas (p < 0.05), cirrosis hepática (p < 0.05), Child-Pugh B y C (p < 0.05) y alfafetoproteína > 20 UI/mL (p 0.20) un año postratamiento, se asociaron al desarrollo de CHC.
Los factores de riesgo para desarrollar CHC fue la presencia de cirrosis hepática, clase funcional Child-Pugh B, varices esofágicas y/o gástricas y genotipo 1b.
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