1,982 research outputs found
Patient-specific three-dimensional explant spheroids derived from human nasal airway epithelium: a simple methodological approach for ex vivo studies of primary ciliary dyskinesia
Clinical and scientific progress related to the interface between cardiology and psychology: lessons learned from 35 years of experience at the Thoraxcenter of the Erasmus Medical Center in Rotterdam
In November 1975, as the first in the Netherlands, a full-time psychologist was employed at the Department of Cardiology of the Thoraxcenter of the Erasmus Medical Center. This innovative decision was consistent with a view to treat the patient as a whole rather than the heart as a single body part in need of repair, combined with the understanding that the heart and mind interact to affect health. The present selective review addresses the broad range of contributions of 35 years of psychology to clinical cardiology and cardiovascular research with a focus on research, teaching, psychological screening and patient care. The review ends with lessons to be learned and challenges for the future with respect to improving the care and management of patients with heart disease in order to enhance secondary prevention and the role of behavioural and psychological factors in this endeavour
Associations between HIV-RNA-based indicators and virological and clinical outcomes
OBJECTIVES: To evaluate and compare the performance of six HIV-RNA-based quality of care indicators for predicting short-term and long-term outcomes. DESIGN: Multinational cohort study. METHODS: We included EuroSIDA patients on antiretroviral therapy (ART) with ≥3viral load (VL) measurements after baseline (the latest of 01/01/2001 or entry into EuroSIDA). Using multivariate Poisson regression we modelled the association between short-term (resistance, triple-class failure) and long-term (all-cause mortality, any AIDS/non-AIDS clinical event) outcomes and the indicators: (i)viraemia copy years (VCY), (ii) Consecutive months with VL ≥50 copies/mL, (iii) percentage of time on ART spent fully suppressed (%FS), (iv) stable on ART, (v)48 weeks snapshot, and (vi) current VL. Indicators were compared using area under the ROC curve (AUC) and different measures of model fit. RESULTS: Adjusted incidence rate ratios for all outcomes tended to increase with increasing VCY, number of consecutive months with VL ≥50 copies/mL, current VL and with lower %FS, but the gradient of increased risk was weak across strata. None of the indicators reliably identified those at risk of long-term outcomes (AUC 0.54-0.58), but performed consistently better with short-term outcomes (triple class failure [AUC 0.67-0.76]) and resistance [AUC 0.64-0.79]). Goodness of fitvariedwith the outcome evaluated, but differences between indicators were small. CONCLUSIONS: Differences between quality of care indicators were small and no indicator performed consistently better than current VL. Given the simplicity in assessing and interpreting this indicator, wepropose to use current VL when HIV-RNA-based indicators are used to evaluate the efficacy of ART programs
Understanding psychiatric institutionalization: a conceptual review
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Modulation of the virus-receptor interaction by mutations in the V5 loop of feline immunodeficiency virus (FIV) following in vivo escape from neutralising antibody
<b>BACKGROUND:</b> In the acute phase of infection with feline immunodeficiency virus (FIV), the virus targets activated CD4+ T cells by utilising CD134 (OX40) as a primary attachment receptor and CXCR4 as a co-receptor. The nature of the virus-receptor interaction varies between isolates; strains such as GL8 and CPGammer recognise a "complex" determinant on CD134 formed by cysteine-rich domains (CRDs) 1 and 2 of the molecule while strains such as PPR and B2542 require a more "simple" determinant comprising CRD1 only for infection. These differences in receptor recognition manifest as variations in sensitivity to receptor antagonists. In this study, we ask whether the nature of the virus-receptor interaction evolves in vivo.<p></p>
<b>RESULTS:</b> Following infection with a homogeneous viral population derived from a pathogenic molecular clone, a quasispecies emerged comprising variants with distinct sensitivities to neutralising antibody and displaying evidence of conversion from a "complex" to a "simple" interaction with CD134. Escape from neutralising antibody was mediated primarily by length and sequence polymorphisms in the V5 region of Env, and these alterations in V5 modulated the virus-receptor interaction as indicated by altered sensitivities to antagonism by both anti-CD134 antibody and soluble CD134.<p></p>
<b>CONCLUSIONS:</b> The FIV-receptor interaction evolves under the selective pressure of the host humoral immune response, and the V5 loop contributes to the virus-receptor interaction. Our data are consistent with a model whereby viruses with distinct biological properties are present in early versus late infection and with a shift from a "complex" to a "simple" interaction with CD134 with time post-infection.<p></p>
Objective assessment of dietary patterns using metabolic phenotyping: a randomized, controlled, crossover trial
Background: The burden of non-communicable diseases, such as obesity, diabetes, coronary heart disease and cancer, can be reduced by the consumption of healthy diets. Accurate monitoring of changes in dietary patterns in response to food policy implementation is challenging. Metabolic profiling allows simultaneous measurement of hundreds of metabolites in urine, many of them influenced by food intake. We aim to classify people according to dietary behaviour and enhance dietary reporting using metabolic profiling of urine. Methods: To develop metabolite models from 19 healthy volunteers who attended a clinical research unit for four day periods on four occasions. We used the World Health Organisation’s healthy eating guidelines (increase fruits, vegetables, wholegrains, dietary fibre and decrease fats, sugars, and salt) to develop four dietary interventions lasting for four days each that ranged from a diet associated with a low to high risk of developing non-communicable disease. Urine samples were measured by 1H-NMR spectroscopy. This study is registered as an International Standard Randomized Controlled Trial, number ISRCTN 43087333. INTERMAP U.K. (n=225) and a healthy-eating Danish cohort (n=66) were used as free-living validation datasets. Findings: There was clear separation between the urinary metabolite profiles of the four diets. We also demonstrated significant stepwise differences in metabolite levels between the lowest and highest metabolic risk diets and developed metabolite models for each diet. Application of the derived metabolite models to independent cohorts confirmed the association between urinary metabolic and dietary profiles in INTERMAP (P<0•001) and the Danish cohort (P<0•001). Interpretation: Urinary metabolite models, developed in a highly controlled environment, can classify groups of free-living people into consumers of dietary profiles associated with lower or higher non-communicable disease risk based on multivariate metabolite patterns. This approach enables objective monitoring of dietary patterns in population settings and enhances validity of dietary reporting. Funding: National Institute for Health Research (NIHR) and Medical Research Council (MRC)
Genetic susceptibility to therapy-related leukemia after Hodgkin lymphoma or non-Hodgkin lymphoma: role of drug metabolism, apoptosis and DNA repair
Edible crabs “Go West”: migrations and incubation cycle of Cancer pagurus revealed by electronic tags
Crustaceans are key components of marine ecosystems which, like other exploited marine taxa, show seasonable patterns of distribution and activity, with consequences for their availability to capture by targeted fisheries. Despite concerns over the sustainability of crab fisheries worldwide, difficulties in observing crabs’ behaviour over their annual cycles, and the timings and durations of reproduction, remain poorly understood. From the release of 128 mature female edible crabs tagged with electronic data storage tags (DSTs), we demonstrate predominantly westward migration in the English Channel. Eastern Channel crabs migrated further than western Channel crabs, while crabs released outside the Channel showed little or no migration. Individual migrations were punctuated by a 7-month hiatus, when crabs remained stationary, coincident with the main period of crab spawning and egg incubation. Incubation commenced earlier in the west, from late October onwards, and brooding locations, determined using tidal geolocation, occurred throughout the species range. With an overall return rate of 34%, our results demonstrate that previous reluctance to tag crabs with relatively high-cost DSTs for fear of loss following moulting is unfounded, and that DSTs can generate precise information with regards life-history metrics that would be unachievable using other conventional means
Inter-population variations in concentrations, determinants of and correlations between 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE): a cross-sectional study of 3161 men and women from Inuit and European populations.
The study is part of a collaborative project (Inuendo), aiming to assess the impact of dietary persistent organochlorine pollutants (POPs) on human fertility. The aims with the present study are to analyze inter-population variations in serum concentrations of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE), to assess inter-population variations in biomarker correlations, and to evaluate the relative impact of different determinants for the inter-individual variations in POP-biomarkers. CB-153 concentrations were much higher in Inuits and Swedish fishermen's populations than in the populations from Eastern Europe, whereas the pattern was different for p,p'-DDE showing highest concentrations in the Kharkiv population. The correlations between the POP-biomarkers varied considerably between the populations, underlining that exposure sources differ and that the choice of representative biomarkers of overall POP exposure has to be based on an analysis of the specific exposure situation for each population. Age and gender were consistent determinants of serum POPs; seafood was of importance only in the Inuit and Swedish populations
The small GTPase Rab29 is a common regulator of immune synapse assembly and ciliogenesis
Acknowledgements We wish to thank Jorge Galán, Gregory Pazour, Derek Toomre, Giuliano Callaini, Joel Rosenbaum, Alessandra Boletta and Francesco Blasi for generously providing reagents and for productive discussions, and Sonia Grassini for technical assistance. The work was carried out with the financial support of Telethon (GGP11021) and AIRC.Peer reviewedPostprin
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