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Pulmonary hypertension is a complex and progressive condition that is either idiopathic or heritable, or associated with one or multiple health conditions, with or without congenital or acquired cardiovascular disease. Recent developments have tremendously increased the armamentarium of diagnostic and therapeutic approaches in children and young adults with pulmonary hypertension that is still associated with a high morbidity and mortality. These modalities include non-invasive imaging, pharmacotherapy, interventional and surgical procedures, and supportive measures. The optimal, tailored diagnostic and therapeutic strategies for pulmonary hypertension in the young are rapidly evolving but still face enormous challenges: Healthcare providers need to take the patient’s age, development, disease state, and family concerns into account when initiating advanced diagnostics and treatment. Therefore, there is a need for guidance on core and advanced medical training in paediatric pulmonary hypertension. The Association for European Paediatric and Congenital Cardiology working group “pulmonary hypertension, heart failure and transplantation” has produced this document as an expert consensus statement; however, all recommendations must be considered and applied in the context of the local and national infrastructure and legal regulations.
The Hkakabo Razi region located in northern Myanmar is an Important Bird Area and part of the Eastern Himalayan Biodiversity Hotspot. Within the framework of the World Heritage Convention to enlist the site under criterion (ix) and (x), we conducted a biodiversity assessment for passerine birds using DNA barcoding and other molecular markers. Of the 441 bird species recorded, we chose 16 target species for a comparative phylogeographic study. Genetic analysis was performed for a larger number of species and helped identifying misidentified species. We found phylogeographic structure in all but one of the 16 study species. In 13 species, populations from northern Myanmar were genetically distinctive and local mitochondrial lineages differed from those found in adjacent regions by 3.9–9.9% uncorrected genetic distances (cytochrome-b). Since the genetic distinctiveness of study populations will be corroborated by further differences in morphology and song as in other South-East Asian passerines, many of them will be candidates for taxonomic splits, or in case an older taxon name is not available, for the scientific description of new taxa. Considering the short time frame of our study we predict that a great part of undetected faunal diversity in the Hkakabo Razi region will be discovered.
Clinical observations indicate that patients with advanced cancer and depression report higher symptom burden than nondepressed patients. This is rarely examined empirically. Study aim was to investigate the association between self-reported depression disorder (DD) and symptoms in patients with advanced cancer controlled for prognostic factors.
The sample included 935 patients, mean age 62, 52% males, from an international multicentre observational study (European Palliative Care Research Collaborative – Computerised Symptom Assessment and Classification of Pain, Depression and Physical Function). DD was assessed by the Patient Health Questionnaire-9 and scored with Diagnostic and Statistical Manual of Mental Disorder-5 algorithm for major depressive disorder, excluding somatic symptoms. Symptom burden was assessed by summing scores on somatic Edmonton Symptom Assessment Scale (ESAS) symptoms, excluding depression, anxiety, and well-being. Item-by-item scores and symptom burden of those with and without DD were compared using nonparametric Mann-Whitney U tests. The relative importance of sociodemographic, medical, and prognostic factors and DD in predicting symptom burden was assessed by hierarchical, multiple regression analyses.
Patients with DD reported significantly higher scores on ESAS items and a twofold higher symptom burden compared with those without. Factors associated with higher symptom burden were as follows. Diagnosis: lung (β = 0.15, p < 0.001) or breast cancer (β = 0.08, p < 0.05); poorer prognosis: high C-reactive protein (β = 0.08, p < 0.05), lower Karnofsky Performance Status (β = −0.14, p < 0.001), and greater weight loss (β = −0.15, p < 0.001); taking opioids (β = 0.11, p < 0.01); and having DD (β = 0.23, p < 0.001). The full model explained 18% of the variance in symptom burden. DD explained 4.4% over and above that explained by all the other variables.
Significance of results
Depression in patients with advanced cancer is associated with higher symptom burden. These results encourage improved routines for identifying and treating those suffering from depression.
Cyclooxygenase inhibitors are widely applied to facilitate ductal closure in preterm infants. The mechanisms that lead to patent ductus arteriosus closure are incompletely understood. Vascular endothelial growth factor plays pivotal roles during ductal closure and remodelling.
The aim of this study was to investigate the effects of ibuprofen and indomethacin on the expression of vascular endothelial growth factor and its receptors in a primary rat ductus arteriosus endothelial cell culture.
Protein expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 1 and 2 was confirmed in rat ductus arteriosus and aorta by immunofluorescence staining. Fetal rat endothelial cells were isolated from ductus arteriosus and aorta using immunomagnetic cell sorting and treated with ibuprofen or indomethacin. mRNA expression levels were assessed by quantitative polymerase chain reaction analysis.
In ductal endothelial cells, ibuprofen significantly induced vascular endothelial growth factor and its receptor 2, but not receptor 1, whereas indomethacin did not alter the expression levels of the vascular endothelial growth factor system. In contrast, ibuprofen significantly induced vascular endothelial growth factor and its receptors 1 and 2 in aortic endothelial cells, whereas indomethacin only induced vascular endothelial growth factor receptor 2.
Our results indicate differential effects of ibuprofen and indomethacin on the expression levels of the vascular endothelial growth factor system in ductus arteriosus endothelial cells. In addition, vessel-specific differences between ductal and aortic endothelial cells were found. Further in vivo studies are needed to elucidate the biological significance of these findings.
User involvement has become an explicit goal within social service provision. Even so, the term remains ambiguous, and its implementation troublesome. Implementation theory lists a number of factors influencing bureaucratic behaviour; in this paper we investigate the ‘human factor’. Our ambition is to provide a framework for analysis of user influence in activation programmes that includes the individual characteristics of both service users and service providers. Building on theoretical insights from the literature on activation and agency, we develop a framework that distinguishes between two ideal types of service users: Pawns and Queens, and two types of service providers: care-oriented Carers and rule-oriented Clerks. This framework is then applied to identify key challenges for the interaction between users and caseworkers in two challenging situations: when service users express little or no agency and when they express agency that is incompatible with the overall goals of the programme. We find that Carers show pronounced reluctance to overrule the choices made by service users even when they have conflicting views – and tend to postpone decisions when they interact with Pawns. Clerks tend to overrule the decisions of Queens when they have conflicting views, and to make decisions on behalf of Pawns. The analysis draws on data collected from 126 qualitative interviews with service providers and participants in the Norwegian Introductory Programme for immigrants and a survey of 320 caseworkers.
Subjects with the metabolic syndrome (MetS) have enhanced oxidative stress and inflammation. Dietary fat quality has been proposed to be implicated in these conditions. We investigated the impact of four diets distinct in fat quantity and quality on 8-iso-PGF2α (a major F2-isoprostane and oxidative stress indicator), 15-keto-13,14-dihydro-PGF2α (15-keto-dihydro-PGF2α, a major PGF2α metabolite and marker of cyclooxygenase-mediated inflammation) and C-reactive protein (CRP). In a 12-week parallel multicentre dietary intervention study (LIPGENE), 417 volunteers with the MetS were randomly assigned to one of the four diets: two high-fat diets (38 % energy (%E)) rich in SFA or MUFA and two low-fat high-complex carbohydrate diets (28 %E) with (LFHCC n-3) or without (LFHCC) 1·24 g/d of very long chain n-3 fatty acid supplementation. Urinary levels of 8-iso-PGF2α and 15-keto-dihydro-PGF2α were determined by RIA and adjusted for urinary creatinine levels. Serum concentration of CRP was measured by ELISA. Neither concentrations of 8-iso-PGF2α and 15-keto-dihydro-PGF2α nor those of CRP differed between diet groups at baseline (P>0·07) or at the end of the study (P>0·44). Also, no differences in changes of the markers were observed between the diet groups (8-iso-PGF2α, P = 0·83; 15-keto-dihydro-PGF2α, P = 0·45; and CRP, P = 0·97). In conclusion, a 12-week dietary fat modification did not affect the investigated markers of oxidative stress and inflammation among subjects with the MetS in the LIPGENE study.
Hypertension is a key feature of the metabolic syndrome. Lifestyle and dietary changes may affect blood pressure (BP), but the knowledge of the effects of dietary fat modification in subjects with the metabolic syndrome is limited. The objective of the present study was to investigate the effect of an isoenergetic change in the quantity and quality of dietary fat on BP in subjects with the metabolic syndrome. In a 12-week European multi-centre, parallel, randomised controlled dietary intervention trial (LIPGENE), 486 subjects were assigned to one of the four diets distinct in fat quantity and quality: two high-fat diets rich in saturated fat or monounsaturated fat and two low-fat, high-complex carbohydrate diets with or without 1·2 g/d of very long-chain n-3 PUFA supplementation. There were no overall differences in systolic BP (SBP), diastolic BP or pulse pressure (PP) between the dietary groups after the intervention. The high-fat diet rich in saturated fat had minor unfavourable effects on SBP and PP in males.
Background: This study examines the effectiveness of a nursing home staff training program designed to improve the interaction between residents with dementia and their caregivers.
Methods: A three-arm cluster-randomized and controlled population of 96 caregivers and 210 residents was used. Caregivers of the intervention group (IG) received a three-month training program in dementia care. Data were gathered at baseline, immediately after the training and at a six-month follow-up-assessment. Short- and long-term effects of the training program were assessed in comparison with another intervention referred to as the relaxation group (RG) and a wait-list control group (CG).
Results: Results indicated significant positive effects of the training program on caregivers' knowledge immediately after the training and on the use of physical restraints at the six-month follow-up. Caregivers' overall competence increased significantly both in the IG and in the RG. No intervention effects were found on caregivers' level of burnout, their health complaints or on the use of sedative drugs. Relaxation training was more successful in the reduction of caregivers' health complaints.
Conclusions: Results of the study indicate both the effectiveness and the limitations of a general training program in dementia care. The complexity of the nursing home setting potentially needs more complex interventions. Ongoing and continued support of the caregivers, as well as changes in organization and environment, are more likely to be helpful in the long-term improvement in the quality of care. Future research should focus on studies of specific interventions, such as the interesting effects of relaxation training on the caregivers' state of health.
Controlled human intervention trials are required to confirm the hypothesis that dietary fat quality may influence insulin action. The aim was to develop a food-exchange model, suitable for use in free-living volunteers, to investigate the effects of four experimental diets distinct in fat quantity and quality: high SFA (HSFA); high MUFA (HMUFA) and two low-fat (LF) diets, one supplemented with 1·24 g EPA and DHA/d (LFn-3). A theoretical food-exchange model was developed. The average quantity of exchangeable fat was calculated as the sum of fat provided by added fats (spreads and oils), milk, cheese, biscuits, cakes, buns and pastries using data from the National Diet and Nutrition Survey of UK adults. Most of the exchangeable fat was replaced by specifically designed study foods. Also critical to the model was the use of carbohydrate exchanges to ensure the diets were isoenergetic. Volunteers from eight centres across Europe completed the dietary intervention. Results indicated that compositional targets were largely achieved with significant differences in fat quantity between the high-fat diets (39·9 (sem 0·6) and 38·9 (sem 0·51) percentage energy (%E) from fat for the HSFA and HMUFA diets respectively) and the low-fat diets (29·6 (sem 0·6) and 29·1 (sem 0·5) %E from fat for the LF and LFn-3 diets respectively) and fat quality (17·5 (sem 0·3) and 10·4 (sem 0·2) %E from SFA and 12·7 (sem 0·3) and 18·7 (sem 0·4) %E MUFA for the HSFA and HMUFA diets respectively). In conclusion, a robust, flexible food-exchange model was developed and implemented successfully in the LIPGENE dietary intervention trial.
The ionic and isotopic characteristics of bulk waters emanating from the cold-based Longyearbreen, central Svalbard, in 2004 are examined to determine lithological, hydrological and glaciological controls on water composition, solute provenance and chemical denudation. The geology consisted of reactive coal seams and associated sedimentary rocks. Acidity caused by microbial-mediated oxidation of sulfides and, to a lesser extent, nitrogen-bearing minerals was neutralized by congruent dissolution of dolomite and incongruent weathering of silicates in open-system subglacial drainage channels. The ablation season was divided into an early melt season, a peak-flow period and a late melt season. The runoff distribution during these periods was 1.7%, 89.7% and 8.6%, respectively, whereas the solute flux distribution was 1.9%, 82.1% and 16.0%, respectively. Comparisons between different annual solute flux estimation methods indicated that extrapolation of peak-flow period data significantly underestimated both the early- and late-melt-season solute fluxes. About 3.8% of the solutes derived from sea-salt spray, 0.7% from acid aerosol deposition and 95.5% from crustal/organic sources. The physical and chemical conditions resulted in diffusion of CO2 rather than atmospheric drawdown. The cation-equivalent weathering rate and the crustal solute yield were 322 ΣmEq+m−2 a−1 and 22 t km−2 a−1, respectively, which are within the regional range of Svalbard. However, the chemical weathering intensity was as high as 940 ΣmEq+ m−3 owing to the relatively low specific discharge of 0.34 m a−1.
Background: We reviewed studies of in-service interventions for caregivers of persons with dementia in nursing homes published between 1990 and 2004. The aim was to obtain an overview of the evaluated interventions and to characterize their methodological quality.
Methods: A thorough literature search was conducted, including searching electronic databases for selected intervention studies and previous reviews. Selected studies were summarized and compared along certain categories, and methodological quality was assessed.
Results: A total of 21 studies were identified, mostly published in the United States. Most were of poor methodological quality. Although nearly all reported positive effects, their results must be interpreted cautiously due to methodological weaknesses. Extensive interventions with ongoing support successfully demonstrated sustained implementation of new knowledge. Owing to methodological weaknesses and a lack of follow-up evaluations, little or no evidence existed for the efficacy or, particularly, the transfer of knowledge in simpler interventions when reinforcing and enabling factors were not present.
Conclusion: On an international and, particularly, on a national level a lack of evaluated in-service training programs for caregivers in homes for people with dementia is apparent. Methodological weakness is common. This study highlights the need for well-defined methodologically improved studies, providing conclusive evidence of the effects of intervention types to help improve the quality of dementia care.
The immune system exists to protect the host against pathogenic organisms and highly complex pathways of recognition, response, elimination and memory have evolved in order to fulfil this role. The immune system also acts to ensure tolerance to ‘self’, to food and other environmental components, and to commensal bacteria. A breakdown in the tolerogenic pathways can also lead to inflammatory diseases. The prevalence of inflammatory diseases, including atopic disorders, has increased over the last 60 years. The development of tolerance is the result of active immune mechanisms and both development and maintenance of tolerance are lifelong processes which start very early in life, even prenatally. Profound immunologic changes occur during pregnancy, involving a polarization of T helper (Th) cells towards a dominance of Th2 and regulatory T cell effector responses in both mother and fetus. This situation is important to maintain pregnancy through avoidance of the rejection of the immunologically incompatible fetus. During the third trimester of human pregnancy, fetal T cells are able to mount antigen-specific responses to environmental and food-derived antigens and antigen-specific T cells are detectable in cord blood in virtually all newborns indicating in utero sensitization. If the neonatal immune system is not able to down-regulate the pre-existing Th2 dominance effectively then an allergic phenotype may develop. Changes occur at, and soon after, birth in order that the immune system of the neonate becomes competent and functional and that the gut becomes colonized with bacteria. Exposure to bacteria during birth and from the mother's skin and the provision of immunologic factors in breast milk are amongst the key events that promote maturation of the infant's gut and gut-associated and systemic immune systems. The introduction of formula and of solid foods exposes the infant to novel food antigens and also affects the gut flora. Nutrition may be the source of antigens to which the immune system must become tolerant, provide factors, including nutrients, that themselves might modulate immune maturation and responses, and provide factors that influence intestinal flora, which in turn will affect antigen exposure, immune maturation and immune responses. Through these mechanisms it is possible that nutrition early in life might affect later immune competence, the ability to mount an appropriate immune response upon infection, the ability to develop a tolerogenic response to ‘self’ and to benign environmental antigens, and the development of immunologic disorders. A Workshop held in February 2006 considered recent findings in the areas of oral tolerance, routes of sensitization to allergens and factors affecting the development of atopic disease; factors influencing the maturation of dendritic cells and the development of regulatory T cells; the influence of gut microflora on immunity, allergic sensitization and infectious disease; the role of nutrition in preventing necrotizing enterocolitis in an animal model of preterm birth; and the role of PUFA of different classes in influencing immune responses and in shaping the development of atopic disease. This report summarizes the content of the lectures and the subsequent discussions.
This study presents an NMR-based metabonomic approach to elucidate the overall endogenous biochemical effects of a wholegrain diet. Two diets with similar levels of dietary fibre and macronutrients, but with contrasting levels of wholegrain ingredients, were prepared from wholegrain rye (wholegrain diet (WGD)) and non-wholegrain wheat (non-wholegrain diet (NWD)) and fed to four pigs in a crossover design. Plasma samples were collected after 7 d on each diet, and 1H NMR spectra were acquired on these. Partial least squares regression discriminant analysis (PLSDA) on spectra obtained for plasma samples revealed that the spectral region at 3·25 parts per million dominates the differentiation between the two diets, as the WGD is associated with higher spectral intensity in this region. Spiking experiments and LC–MS analyses of the plasma verified that this spectral difference could be ascribed to a significantly higher content of betaine in WGD plasma samples compared with NWD samples. In an identical study with the same diets, urine samples were collected, and1H NMR spectra were acquired on these. PLS-DA on spectra obtained for urine samples revealed changes in the intensities of spectral regions, which could be ascribed to differences in the content of betaine and creatine/creatinine between the two diets, and LC–MS analyses verified a significantly lower content of creatinine in WGD urine samples compared with NWD urine samples. In conclusion, using an explorative approach, the present studies disclosed biochemical effects of a wholegrain diet on plasma betaine content and excretion of betaine and creatinine.