• Konspekt
• Farmacie. Farmakologie
• NLK Obory
• farmacie a farmakologie
• farmacie a farmakologie

OBJECTIVE: To provide a new perspective on integrated biomedical and psychosocial dementia research. BACKGROUND: Dementia is being recognized as a multifactorial syndrome, but there is little interaction between biomedical and psychosocial approaches. A way to improve scientific knowledge is to seek better understanding of the mechanisms underlying the interaction between biomedical and psychosocial paradigms. One rationale for integrating biomedical and psychosocial research is the discordance between neuropathology and cognitive functioning. The concept of social health might bridge the two paradigms. It relates to how social resources influence the dynamic balance between capacities and limitations. HYPOTHESES: Social health can act as the driver for accessing cognitive reserve, in people with dementia through active facilitation and utilization of social and environmental resources. Thereby we link lifestyle social and opportunities to the brain reserve hypothesis. MANIFESTO: We provide a Manifesto on how to significantly move forward the dementia research agenda.

• MeSH
• demence * MeSH
• kognitivní rezerva * MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

In this study, a novel harvesting emulsion (HEM) consisting of cooking oil in an aqueous solution of cetyltrimethylammonium bromide (CTAB) was tested for the harvesting of a technologically important microalga, Chlorella vulgaris. The influence of HEM dose, biomass and bovine serum albumin (BSA) (model interferer compound) on harvesting efficiency (E) were studied. The HEM E was over 90% at pH 10 (0.33% (v/v) cooking oil, 6.7 mg/L of CTAB) and 12 (0.13% (v/v) cooking oil, 2.7 mg/L of CTAB). Harvesting efficiencies at pH 4 and 7 were < 73.5% due to the absence of precipitate formation. Bovine serum albumin (10 mg/L) increased the HEM dose necessary to achieve E ˃ 90% by 1.2 (pH 10), and 3 fold (pH 12). By manipulating the dose of HEM and pH, the method of harvesting (flocculation/sedimentation or flotation) was adjustable depending on the technological requirements.

• MeSH
• biomasa MeSH
• Chlorella vulgaris * MeSH
• flokulace MeSH
• mikrořasy * MeSH
• povrchově aktivní látky MeSH
• vaření MeSH
• voda MeSH
• Publikační typ
• časopisecké články MeSH

The extent of translational control of gene expression in mammalian tissues remains largely unknown. Here we perform genome-wide RNA sequencing and ribosome profiling in heart and liver tissues to investigate strain-specific translational regulation in the spontaneously hypertensive rat (SHR/Ola). For the most part, transcriptional variation is equally apparent at the translational level and there is limited evidence of translational buffering. Remarkably, we observe hundreds of strain-specific differences in translation, almost doubling the number of differentially expressed genes. The integration of genetic, transcriptional and translational data sets reveals distinct signatures in 3'UTR variation, RNA-binding protein motifs and miRNA expression associated with translational regulation of gene expression. We show that a large number of genes associated with heart and liver traits in human genome-wide association studies are primarily translationally regulated. Capturing interindividual differences in the translated genome will lead to new insights into the genes and regulatory pathways underlying disease phenotypes.

• MeSH
• fenotyp MeSH
• hypertenze metabolismus   MeSH
• játra metabolismus   MeSH
• myokard metabolismus   MeSH
• potkani inbrední BN MeSH
• potkani inbrední SHR MeSH
• proteom MeSH
• regulace genové exprese * MeSH
• ribozomy metabolismus   MeSH
• sekvenční analýza RNA MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The fully grown mammalian oocyte is transcriptionally quiescent and utilizes only transcripts synthesized and stored during early development. However, we find that an abundant RNA population is retained in the oocyte nucleus and contains specific mRNAs important for meiotic progression. Here we show that during the first meiotic division, shortly after nuclear envelope breakdown, translational hotspots develop in the chromosomal area and in a region that was previously surrounded the nucleus. These distinct translational hotspots are separated by endoplasmic reticulum and Lamin, and disappear following polar body extrusion. Chromosomal translational hotspots are controlled by the activity of the mTOR-eIF4F pathway. Here we reveal a mechanism that-following the resumption of meiosis-controls the temporal and spatial translation of a specific set of transcripts required for normal spindle assembly, chromosome alignment and segregation.

• MeSH
• časové faktory MeSH
• down regulace MeSH
• eukaryotický iniciační faktor 4F metabolismus   MeSH
• fertilizace MeSH
• jaderný obal metabolismus   MeSH
• lidé MeSH
• meióza MeSH
• messenger RNA genetika   metabolismus   MeSH
• myši MeSH
• nestabilita genomu MeSH
• oocyty metabolismus   MeSH
• proteosyntéza * MeSH
• RNA čepičky metabolismus   MeSH
• savčí chromozomy metabolismus   MeSH
• savci metabolismus   MeSH
• signální transdukce * MeSH
• TOR serin-threoninkinasy metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Treatment options in multiple myeloma (MM) are increasing with the introduction of complex multi-novel-agent-based regimens investigated in randomized clinical trials. However, application in the real-world setting, including feasibility of and adherence to these regimens, may be limited due to varying patient-, treatment-, and disease-related factors. Furthermore, approximately 40% of real-world MM patients do not meet the criteria for phase 3 studies on which approvals are based, resulting in a lack of representative phase 3 data for these patients. Therefore, treatment decisions must be tailored based on additional considerations beyond clinical trial efficacy and safety, such as treatment feasibility (including frequency of clinic/hospital attendance), tolerability, effects on quality of life (QoL), and impact of comorbidities. There are multiple factors of importance to real-world MM patients, including disease symptoms, treatment burden and toxicities, ability to participate in daily activities, financial burden, access to treatment and treatment centers, and convenience of treatment. All of these factors are drivers of QoL and treatment satisfaction/compliance. Importantly, given the heterogeneity of MM, individual patients may have different perspectives regarding the most relevant considerations and goals of their treatment. Patient perspectives/goals may also change as they move through their treatment course. Thus, the 'efficacy' of treatment means different things to different patients, and treatment decision-making in the context of personalized medicine must be guided by an individual's composite definition of what constitutes the best treatment choice. This review summarizes the various factors of importance and practical issues that must be considered when determining real-world treatment choices. It assesses the current instruments, methodologies, and recent initiatives for analyzing the MM patient experience. Finally, it suggests options for enhancing data collection on patients and treatments to provide a more holistic definition of the effectiveness of a regimen in the real-world setting.

• MeSH
• antitumorózní látky škodlivé účinky   terapeutické užití   MeSH
• klinické zkoušky, fáze III jako téma MeSH
• kvalita života MeSH
• lidé MeSH
• management nemoci MeSH
• mnohočetný myelom terapie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Histone modifications are epigenetic marks that play fundamental roles in many biological processes including the control of chromatin-mediated regulation of gene expression. Little is known about interindividual variability of histone modification levels across the genome and to what extent they are influenced by genetic variation. We annotated the rat genome with histone modification maps, identified differences in histone trimethyl-lysine levels among strains, and described their underlying genetic basis at the genome-wide scale using ChIP-seq in heart and liver tissues in a panel of rat recombinant inbred and their progenitor strains. We identified extensive variation of histone methylation levels among individuals and mapped hundreds of underlying cis- and trans-acting loci throughout the genome that regulate histone methylation levels in an allele-specific manner. Interestingly, most histone methylation level variation was trans-linked and the most prominent QTL identified influenced H3K4me3 levels at 899 putative promoters throughout the genome in the heart. Cis- acting variation was enriched in binding sites of distinct transcription factors in heart and liver. The integrated analysis of DNA variation together with histone methylation and gene expression levels showed that histoneQTLs are an important predictor of gene expression and that a joint analysis significantly enhanced the prediction of gene expression traits (eQTLs). Our data suggest that genetic variation has a widespread impact on histone trimethylation marks that may help to uncover novel genotype-phenotype relationships.

• MeSH
• epigeneze genetická * MeSH
• genetická transkripce MeSH
• genetická variace * MeSH
• genom * MeSH
• histony genetika   metabolismus   MeSH
• inbrední kmeny potkanů MeSH
• játra metabolismus   MeSH
• krysa rodu rattus MeSH
• lokus kvantitativního znaku MeSH
• metylace MeSH
• myokard metabolismus   MeSH
• posttranslační úpravy proteinů * MeSH
• promotorové oblasti (genetika) MeSH
• transkripční faktory genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• dějiny MeSH
• lékárny dějiny   MeSH
• nádobí dějiny   MeSH
• zdravotnické prostředky dějiny   MeSH

In recent years, numerous foodborne outbreaks due to consumption of berry fruit contaminated by human enteric viruses have been reported. This European multinational study investigated possible contamination routes by monitoring the entire food chain for a panel of human and animal enteric viruses. A total of 785 samples were collected throughout the food production chain of four European countries (Czech Republic, Finland, Poland and Serbia) during two growing seasons. Samples were taken during the production phase, the processing phase, and at point-of-sale. Samples included irrigation water, animal faeces, food handlers' hand swabs, swabs from toilets on farms, from conveyor belts at processing plants, and of raspberries or strawberries at points-of-sale; all were subjected to virus analysis. The samples were analysed by real-time (reverse transcription, RT)-PCR, primarily for human adenoviruses (hAdV) to demonstrate that a route of contamination existed from infected persons to the food supply chain. The analyses also included testing for the presence of selected human (norovirus, NoV GI, NoV GII and hepatitis A virus, HAV), animal (porcine adenovirus, pAdV and bovine polyomavirus, bPyV) and zoonotic (hepatitis E virus, HEV) viruses. At berry production, hAdV was found in 9.5%, 5.8% and 9.1% of samples of irrigation water, food handlers' hands and toilets, respectively. At the processing plants, hAdV was detected in one (2.0%) swab from a food handler's hand. At point-of-sale, the prevalence of hAdV in fresh raspberries, frozen raspberries and fresh strawberries, was 0.7%, 3.2% and 2.0%, respectively. Of the human pathogenic viruses, NoV GII was detected in two (3.6%) water samples at berry production, but no HAV was detected in any of the samples. HEV-contaminated frozen raspberries were found once (2.6%). Animal faecal contamination was evidenced by positive pAdV and bPyV assay results. At berry production, one water sample contained both viruses, and at point-of-sale 5.7% and 1.3% of fresh and frozen berries tested positive for pAdV. At berry production hAdV was found both in irrigation water and on food handler's hands, which indicated that these may be important vehicles by which human pathogenic viruses enter the berry fruit chain. Moreover, both zoonotic and animal enteric viruses could be detected on the end products. This study gives insight into viral sources and transmission routes and emphasizes the necessity for thorough compliance with good agricultural and hygienic practice at the farms to help protect the public from viral infections.

• MeSH
• adenoviry prasat izolace a purifikace   MeSH
• Enterovirus MeSH
• epidemický výskyt choroby MeSH
• feces virologie   MeSH
• kontaminace potravin analýza   MeSH
• lidé MeSH
• lidské adenoviry izolace a purifikace   MeSH
• manipulace s potravinami metody   MeSH
• mikrobiologie vody MeSH
• Norovirus izolace a purifikace   MeSH
• ovoce virologie   MeSH
• Polyomavirus izolace a purifikace   MeSH
• prasata MeSH
• ruka virologie   MeSH
• skot MeSH
• virus hepatitidy A izolace a purifikace   MeSH
• virus hepatitidy E izolace a purifikace   MeSH
• viry MeSH
• zásobování potravinami MeSH
• zemědělské zavlažování MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Finsko MeSH
• Polsko MeSH
• Srbsko MeSH

INTRODUCTION: Effective management of seasonal and pandemic influenza is a high priority internationally. Guidelines in many countries recommend antiviral treatment for older people and individuals with comorbidity at increased risk of complications. However, antivirals are not often prescribed in primary care in Europe, partly because its clinical and cost effectiveness has been insufficiently demonstrated by non-industry funded and pragmatic studies. METHODS AND ANALYSIS: Antivirals for influenza-Like Illness? An rCt of Clinical and Cost effectiveness in primary CarE is a European multinational, multicentre, open-labelled, non-industry funded, pragmatic, adaptive-platform, randomised controlled trial. Initial trial arms will be best usual primary care and best usual primary care plus treatment with oseltamivir for 5 days. We aim to recruit at least 2500 participants ≥1 year presenting with influenza-like illness (ILI), with symptom duration ≤72 hours in primary care over three consecutive periods of confirmed high influenza incidence. Participant outcomes will be followed up to 28 days by diary and telephone. The primary objective is to determine whether adding antiviral treatment to best usual primary care is effective in reducing time to return to usual daily activity with fever, headache and muscle ache reduced to minor severity or less. Secondary objectives include estimating cost-effectiveness, benefits in subgroups according to age (<12, 12-64 and >64 years), severity of symptoms at presentation (low, medium and high), comorbidity (yes/no), duration of symptoms (≤48 hours/>48-72 hours), complications (hospital admission and pneumonia), use of additional prescribed medication including antibiotics, use of over-the-counter medicines and self-management of ILI symptoms. ETHICS AND DISSEMINATION: Research ethics committee (REC) approval was granted by the NRES Committee South Central (Oxford B) and Clinical Trial Authority (CTA) approval by The Medicines and Healthcare products Regulatory Agency. All participating countries gained national REC and CTA approval as required. Dissemination of results will be through peer-reviewed scientific journals and conference presentations. TRIAL REGISTRATION NUMBER: ISRCTN27908921; Pre-results.

• MeSH
• analýza nákladů a výnosů MeSH
• antivirové látky ekonomika   terapeutické užití   MeSH
• bolesti hlavy virologie   MeSH
• časové faktory MeSH
• chřipka lidská komplikace   farmakoterapie   prevence a kontrola   MeSH
• činnosti denního života MeSH
• horečka virologie   MeSH
• hospitalizace MeSH
• léky bez předpisu terapeutické užití   MeSH
• léky na předpis terapeutické užití   MeSH
• lidé MeSH
• multicentrické studie jako téma MeSH
• myalgie virologie   MeSH
• oseltamivir ekonomika   terapeutické užití   MeSH
• péče o sebe MeSH
• pneumonie virologie   MeSH
• pragmatické klinické studie jako téma * MeSH
• určení symptomu MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• protokol klinické studie MeSH