While most guidelines recommend monotherapy with second-generation antipsychotics (SGA) in schizophrenia, the combined application of multiple psychotropic agents is very common, especially in treatment-refractory cases. METHODS: This review summarizes the evidence of combined antipsychotic treatment strategies and the augmentation of antipsychotics with mood stabilizers, antidepressants and experimental substances, based on publications accessible in public databases (Medline/Ovid, Google, http://www.clinicaltrials.gov) up to October 2009. RESULTS: Polypharmacy aims to address several aspects of treatment resistance and side effects of antipsychotics. Some evidence supports the augmentation of antipsychotics with antidepressants for negative symptoms and comorbid major depressive episodes. The add-on of lithium and mood stabilizers lacks compelling evidence but might be beneficial for specific subgroups. For treatment-resistant cognitive symptoms, cognitive re-mediation seems most promising as no pharmacological add-on strategy has gained convincing evidence so far. Acute dystonic movements should be treated with anticholinergic agents while agitation and anxiety might respond to short-term application of benzodiazepines. Treatment-resistant positive and/or negative symptoms should primarily lead to clozapine monotherapy; the add-on of a second SGA may be considered in single cases. CONCLUSIONS: In general, rigorous data on combination therapy in schizophrenia are rare, and further randomized controlled trials (RCT), naturalistic and head-to-head-studies are necessary.

• MeSH
• antipsychotika škodlivé účinky   terapeutické užití   MeSH
• kognitivní poruchy epidemiologie   MeSH
• komorbidita MeSH
• léková rezistence MeSH
• lidé MeSH
• obsedantně kompulzivní porucha epidemiologie   MeSH
• polypharmacy MeSH
• poruchy nálady epidemiologie   MeSH
• schizofrenie epidemiologie   farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

The ability of bacteria to bind different compounds and to adhere to biotic and abiotic surfaces provides them with a range of advantages, such as colonization of various tissues, internalization, avoidance of an immune response, and survival and persistence in the environment. A variety of bacterial surface structures are involved in this process and these promote bacterial adhesion in a more or less specific manner. In this review, we will focus on those surface adhesins and exopolymers in selected foodborne pathogens that are involved mainly in primary adhesion. Their role in biofilm development will also be considered when appropriate. Both the clinical impact and the implications for food safety of such adhesion will be discussed.

• MeSH
• Bacteria metabolismus   MeSH
• bakteriální adheze * MeSH
• bakteriální adheziny analýza   MeSH
• biofilmy růst a vývoj   MeSH
• biopolymery metabolismus   MeSH
• fyziologie bakterií * MeSH
• nemoci přenášené potravou mikrobiologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Cylindrospermopsin (CYN) is a cyanobacterial toxin that occurs in aquatic environments worldwide. It is known for its delayed effects in animals and humans such as inhibition of protein synthesis or genotoxicity. The molecular targets and the cell physiological mechanisms of CYN, however, are not well studied. As inhalation of CYN-containing aerosols has been identified as a relevant route of CYN uptake, we analyzed the effects of CYN on protein expression in cultures of immortalized human bronchial epithelial cells (16HBE14o-) using a proteomic approach. Proteins whose expression levels were affected by CYN belonged to several functional clusters, mainly regulation of protein stability, cellular adhesion and integration in the extracellular matrix, cell proliferation, cell cycle regulation, and completion of cytokinesis. With a few exceptions of upregulated proteins (e.g., ITI inhibitor of serine endopeptidases and mRNA stabilizer PABPC1), CYN mediated the downregulation of many proteins. Among these, centrosomal protein 55 (CEP55) and osteonectin (SPARC) were significantly reduced in their abundance. Results of the detailed semi-quantitative Western blot analyses of SPARC, claudin-6, and CEP55 supported the findings from the proteomic study that epithelial cell adhesion, attenuation of cell proliferation, delayed completion of mitosis, as well as induction of genomic instability are major effects of CYN in eukaryotic cells.

• MeSH
• epitelové buňky * účinky léků   metabolismus   MeSH
• lidé MeSH
• proteiny buněčného cyklu MeSH
• proteomika MeSH
• toxiny kmene Cyanobacteria * toxicita   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Biofilms are widespread in nature and constitute an important strategy implemented by microorganisms to survive in sometimes harsh environmental conditions. They can be beneficial or have a negative impact particularly when formed in industrial settings or on medical devices. As such, research into the formation and elimination of biofilms is important for many disciplines. Several new methodologies have been recently developed for, or adapted to, biofilm studies that have contributed to deeper knowledge on biofilm physiology, structure and composition. In this review, traditional and cutting-edge methods to study biofilm biomass, viability, structure, composition and physiology are addressed. Moreover, as there is a lack of consensus among the diversity of techniques used to grow and study biofilms. This review intends to remedy this, by giving a critical perspective, highlighting the advantages and limitations of several methods. Accordingly, this review aims at helping scientists in finding the most appropriate and up-to-date methods to study their biofilms.

• MeSH
• bakteriální adheze MeSH
• biofilmy * růst a vývoj   MeSH
• databáze faktografické MeSH
• design vybavení MeSH
• hybridizace in situ fluorescenční MeSH
• laboratoř na čipu MeSH
• mikrobiologické techniky přístrojové vybavení   metody   MeSH
• mikroskopie metody   MeSH
• molekulární biologie metody   MeSH
• počítačové zpracování obrazu metody   MeSH
• software MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Hepatorenal tyrosinaemia (HT1) is an autosomal recessive disorder of tyrosine degradation resulting in hepatic and renal dysfunction, neurological sequelae may occur in some patients. The use of nitisinone (NTBC) has revolutionised treatment and outcome of this disorder. NTBC has to be combined with a low protein diet. While NTBC modulates the disease course in HT1 patients, several issues are open. Optimal dosage, doses per day, therapeutic range of NTBC concentration, mode of protein restriction and biomarkers are not well defined. HCC and neurocognitive deficits are long-term sequelae. Early diagnosis and treatment are essential to minimise the risk for these complications. Clinical guidance for management of HT1-patients is required. Randomised clinical studies are difficult in the presence of therapeutic options. We discussed these issues in a consensus group of 10 paediatricians, 1 adult hepatologist, 1 geneticist, 2 dieticians, 2 newborn screening specialists with experience in HT1, 1 psychologist and 2 representatives of a patient group from the German-speaking countries (DACH). Recommendations were based on scientific literature and expert opinion, also taking into account recent experience with newborn screening. There was strong consensus that newborn screening using succinylacetone (SA) and early treatment are essential for a good outcome. The dose of NTBC should be as low as possible without losing metabolic control. This has to be accompanied by a low protein diet, in some patients a simplified diet without calculation of protein intake. Specific education and psychosocial support are recommended. Indications for liver transplantation were defined. Monitoring shall include clinical findings, levels of SA, tyrosine, phenylalanine and NTBC in (dried) blood.

• MeSH
• cyklohexanony * terapeutické užití   MeSH
• heptanoáty MeSH
• konsensus MeSH
• lidé MeSH
• nitrobenzoany * terapeutické užití   MeSH
• nízkoproteinová dieta MeSH
• novorozenec MeSH
• novorozenecký screening * metody   MeSH
• transplantace jater MeSH
• tyrosinemie * diagnóza   terapie   MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Německo MeSH

BACKGROUND: Hepatorenal tyrosinaemia (Tyr 1) is a rare inborn error of tyrosine metabolism. Without treatment, patients are at high risk of developing acute liver failure, renal dysfunction and in the long run hepatocellular carcinoma. The aim of our study was to collect cross-sectional data. METHODS: Via questionnaires we collected retrospective data of 168 patients with Tyr 1 from 21 centres (Europe, Turkey and Israel) about diagnosis, treatment, monitoring and outcome. In a subsequent consensus workshop, we discussed data and clinical implications. RESULTS: Early treatment by NTBC accompanied by diet is essential to prevent serious complications such as liver failure, hepatocellular carcinoma and renal disease. As patients may remain initially asymptomatic or develop uncharacteristic clinical symptoms in the first months of life newborn mass screening using succinylacetone (SA) as a screening parameter in dried blood is mandatory for early diagnosis. NTBC-treatment has to be combined with natural protein restriction supplemented with essential amino acids. NTBC dosage should be reduced to the minimal dose allowing metabolic control, once daily dosing may be an option in older children and adults in order to increase compliance. Metabolic control is judged by SA (below detection limit) in dried blood or urine, plasma tyrosine (<400 μM) and NTBC-levels in the therapeutic range (20-40 μM). Side effects of NTBC are mild and often transient. Indications for liver transplantation are hepatocellular carcinoma or failure to respond to NTBC. Follow-up procedures should include liver and kidney function tests, tumor markers and imaging, ophthalmological examination, blood count, psychomotor and intelligence testing as well as therapeutic monitoring (SA, tyrosine, NTBC in blood). CONCLUSION: Based on the data from 21 centres treating 168 patients we were able to characterize current practice and clinical experience in Tyr 1. This information could form the basis for clinical practice recommendations, however further prospective data are required to underpin some of the recommendations.

• MeSH
• cyklohexanony škodlivé účinky   terapeutické užití   MeSH
• dítě MeSH
• inhibitory enzymů škodlivé účinky   terapeutické užití   MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• následné studie MeSH
• nitrobenzoany škodlivé účinky   terapeutické užití   MeSH
• novorozenec MeSH
• novorozenecký screening metody   MeSH
• předškolní dítě MeSH
• průřezové studie MeSH
• průzkumy a dotazníky MeSH
• renální insuficience diagnóza   chirurgie   MeSH
• retrospektivní studie MeSH
• selhání jater diagnóza   chirurgie   MeSH
• transplantace jater MeSH
• tyrosinemie diagnóza   terapie   MeSH
• výsledek terapie MeSH
• vzácné nemoci diagnóza   farmakoterapie   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

Hypothermia versus Normothermia after Cardiac ArrestHolgersson et al. perform an individual patient data meta-analysis of the TTM and TTM2 trials of hypothermia after cardiac arrest and find no difference in 6-month mortality with hypothermia to 33°C versus normothermia.

• MeSH
• hypotermie * MeSH
• lidé MeSH
• srdeční zástava * terapie   MeSH
• tělesná teplota MeSH
• teplota MeSH
• terapeutická hypotermie * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH

Common variation in the gene encoding the neuron-specific RNA splicing factor RNA Binding Fox-1 Homolog 1 (RBFOX1) has been identified as a risk factor for several psychiatric conditions, and rare genetic variants have been found causal for autism spectrum disorder (ASD). Here, we explored the genetic landscape of RBFOX1 more deeply, integrating evidence from existing and new human studies as well as studies in Rbfox1 knockout mice. Mining existing data from large-scale studies of human common genetic variants, we confirmed gene-based and genome-wide association of RBFOX1 with risk tolerance, major depressive disorder and schizophrenia. Data on six mental disorders revealed copy number losses and gains to be more frequent in ASD cases than in controls. Consistently, RBFOX1 expression appeared decreased in post-mortem frontal and temporal cortices of individuals with ASD and prefrontal cortex of individuals with schizophrenia. Brain-functional MRI studies demonstrated that carriers of a common RBFOX1 variant, rs6500744, displayed increased neural reactivity to emotional stimuli, reduced prefrontal processing during cognitive control, and enhanced fear expression after fear conditioning, going along with increased avoidance behaviour. Investigating Rbfox1 neuron-specific knockout mice allowed us to further specify the role of this gene in behaviour. The model was characterised by pronounced hyperactivity, stereotyped behaviour, impairments in fear acquisition and extinction, reduced social interest, and lack of aggression; it provides excellent construct and face validity as an animal model of ASD. In conclusion, convergent translational evidence shows that common variants in RBFOX1 are associated with a broad spectrum of psychiatric traits and disorders, while rare genetic variation seems to expose to early-onset neurodevelopmental psychiatric disorders with and without developmental delay like ASD, in particular. Studying the pleiotropic nature of RBFOX1 can profoundly enhance our understanding of mental disorder vulnerability.

• MeSH
• celogenomová asociační studie MeSH
• depresivní porucha unipolární * genetika   MeSH
• duševní poruchy * genetika   MeSH
• lidé MeSH
• myši knockoutované MeSH
• myši MeSH
• poruchy autistického spektra * genetika   MeSH
• sestřihové faktory genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Local biodiversity trends over time are likely to be decoupled from global trends, as local processes may compensate or counteract global change. We analyze 161 long-term biological time series (15-91 years) collected across Europe, using a comprehensive dataset comprising ~6,200 marine, freshwater and terrestrial taxa. We test whether (i) local long-term biodiversity trends are consistent among biogeoregions, realms and taxonomic groups, and (ii) changes in biodiversity correlate with regional climate and local conditions. Our results reveal that local trends of abundance, richness and diversity differ among biogeoregions, realms and taxonomic groups, demonstrating that biodiversity changes at local scale are often complex and cannot be easily generalized. However, we find increases in richness and abundance with increasing temperature and naturalness as well as a clear spatial pattern in changes in community composition (i.e. temporal taxonomic turnover) in most biogeoregions of Northern and Eastern Europe.

• MeSH
• biodiverzita * MeSH
• ekosystém * MeSH
• klimatické změny MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH