Pretransplant dyslipidaemia influences primary graft dysfunction after lung transplantation

OBJECTIVES: Primary graft dysfunction (PGD) is a major cause of mortality within the first year following lung transplantation. Pulmonary hypertension, elevated body mass index (BMI), prolonged ischaemic time of the graft, intraoperative blood transfusions >1000 ml and the use of cardiopulmonary bypass or extracorporeal membrane oxygenation increase the risk for PGD. We aimed to evaluate whether dyslipidaemia is an additional risk factor for the development of PGD. METHODS: We retrospectively analysed demographic and clinical data of 264 patients who received their first bilateral lung transplantation between March 2000 and October 2013 at our institution. The endpoint was PGD grade 3 at any time, defined according to the International Society for Heart and Lung Transplantation (ISHLT) criteria. Fasting lipid profiles at listing time or just before transplantation (baseline) were documented and dyslipidaemia was defined as any of the parameters being out of range. Comparisons of continuous variables between patients with PGD grade 3 and patients without were performed with the Mann-Whitney U-test, whereas proportions were compared with the χ(2) test. Continuous variables were presented as arithmetic means with standard deviation for ease of comparison, but levels of statistical significance were computed using the appropriate non-parametric statistical test. To identify PGD risk factors, a forward stepwise logistic regression model was used. RESULTS: PGD occurred in 63 recipients (24%). Pretransplant dyslipidaemia was documented in 153 recipients (58%) and was significantly more prevalent among recipients developing PGD (45 vs 108, P < 0.013). Despite various underlying pulmonary pathologies, higher triglyceride (TG) levels (1.41 ± 0.78 vs 1.16 ± 0.78, P < 0.012), lower high-density lipoprotein-cholesterol (HDL-C) concentrations (1.24 ± 0.55 vs 1.57 ± 0.71, P < 0.0005) and higher cholesterol/HDL-C values (3.80 ± 2.02 vs 3.00 ± 0.92, P < 0.0005) were associated with a lower incidence of PGD. Patients with PGD had significantly longer ischaemic time (350 ± 89 vs 322 ± 91, P = 0.017) and higher BMI (23 ± 5 vs 21 ± 4.4, P < 0.007). CONCLUSION: Dyslipidaemia seems to be an independent risk factor for PGD after lung transplantation: low circulating levels of HDL-C and hypertriglyceridaemia increase the incidence of PGD. Even if HDL-C levels are difficult to alter today, triglyceride and cholesterol levels can be addressed therapeutically and may have a positive influence on the development of PGD

Mental health of returnees: refugees in Germany prior to their state-sponsored repatriation

von Lersner U, Wiens U, Elbert T, Neuner F. Mental health of returnees: refugees in Germany prior to their state-sponsored repatriation. BMC International Health and Human Rights. 2008;8(1): 8

Synapse Geometry and Receptor Dynamics Modulate Synaptic Strength

Synaptic transmission relies on several processes, such as the location of a released vesicle, the number and type of receptors, trafficking between the postsynaptic density (PSD) and extrasynaptic compartment, as well as the synapse organization. To study the impact of these parameters on excitatory synaptic transmission, we present a computational model for the fast AMPA-receptor mediated synaptic current. We show that in addition to the vesicular release probability, due to variations in their release locations and the AMPAR distribution, the postsynaptic current amplitude has a large variance, making a synapse an intrinsic unreliable device. We use our model to examine our experimental data recorded from CA1 mice hippocampal slices to study the differences between mEPSC and evoked EPSC variance. The synaptic current but not the coefficient of variation is maximal when the active zone where vesicles are released is apposed to the PSD. Moreover, we find that for certain type of synapses, receptor trafficking can affect the magnitude of synaptic depression. Finally, we demonstrate that perisynaptic microdomains located outside the PSD impacts synaptic transmission by regulating the number of desensitized receptors and their trafficking to the PSD. We conclude that geometrical modifications, reorganization of the PSD or perisynaptic microdomains modulate synaptic strength, as the mechanisms underlying long-term plasticity

Pretransplant dyslipidaemia influences primary graft dysfunction after lung transplantation

Abstract OBJECTIVES Primary graft dysfunction (PGD) is a major cause of mortality within the first year following lung transplantation. Pulmonary hypertension, elevated body mass index (BMI), prolonged ischaemic time of the graft, intraoperative blood transfusions >1000 ml and the use of cardiopulmonary bypass or extracorporeal membrane oxygenation increase the risk for PGD. We aimed to evaluate whether dyslipidaemia is an additional risk factor for the development of PGD. METHODS We retrospectively analysed demographic and clinical data of 264 patients who received their first bilateral lung transplantation between March 2000 and October 2013 at our institution. The endpoint was PGD grade 3 at any time, defined according to the International Society for Heart and Lung Transplantation (ISHLT) criteria. Fasting lipid profiles at listing time or just before transplantation (baseline) were documented and dyslipidaemia was defined as any of the parameters being out of range. Comparisons of continuous variables between patients with PGD grade 3 and patients without were performed with the Mann-Whitney U-test, whereas proportions were compared with the χ2 test. Continuous variables were presented as arithmetic means with standard deviation for ease of comparison, but levels of statistical significance were computed using the appropriate non-parametric statistical test. To identify PGD risk factors, a forward stepwise logistic regression model was used. RESULTS PGD occurred in 63 recipients (24%). Pretransplant dyslipidaemia was documented in 153 recipients (58%) and was significantly more prevalent among recipients developing PGD (45 vs 108, P < 0.013). Despite various underlying pulmonary pathologies, higher triglyceride (TG) levels (1.41 ± 0.78 vs 1.16 ± 0.78, P < 0.012), lower high-density lipoprotein-cholesterol (HDL-C) concentrations (1.24 ± 0.55 vs 1.57 ± 0.71, P < 0.0005) and higher cholesterol/HDL-C values (3.80 ± 2.02 vs 3.00 ± 0.92, P < 0.0005) were associated with a lower incidence of PGD. Patients with PGD had significantly longer ischaemic time (350 ± 89 vs 322 ± 91, P = 0.017) and higher BMI (23 ± 5 vs 21 ± 4.4, P < 0.007). CONCLUSIONS Dyslipidaemia seems to be an independent risk factor for PGD after lung transplantation: low circulating levels of HDL-C and hypertriglyceridaemia increase the incidence of PGD. Even if HDL-C levels are difficult to alter today, triglyceride and cholesterol levels can be addressed therapeutically and may have a positive influence on the development of PGD

Pretransplant dyslipidaemia influences primary graft dysfunction after lung transplantation

OBJECTIVES: Primary graft dysfunction (PGD) is a major cause of mortality within the first year following lung transplantation. Pulmonary hypertension, elevated body mass index (BMI), prolonged ischaemic time of the graft, intraoperative blood transfusions >1000 ml and the use of cardiopulmonary bypass or extracorporeal membrane oxygenation increase the risk for PGD. We aimed to evaluate whether dyslipidaemia is an additional risk factor for the development of PGD. METHODS: We retrospectively analysed demographic and clinical data of 264 patients who received their first bilateral lung transplantation between March 2000 and October 2013 at our institution. The endpoint was PGD grade 3 at any time, defined according to the International Society for Heart and Lung Transplantation (ISHLT) criteria. Fasting lipid profiles at listing time or just before transplantation (baseline) were documented and dyslipidaemia was defined as any of the parameters being out of range. Comparisons of continuous variables between patients with PGD grade 3 and patients without were performed with the Mann-Whitney U-test, whereas proportions were compared with the χ(2) test. Continuous variables were presented as arithmetic means with standard deviation for ease of comparison, but levels of statistical significance were computed using the appropriate non-parametric statistical test. To identify PGD risk factors, a forward stepwise logistic regression model was used. RESULTS: PGD occurred in 63 recipients (24%). Pretransplant dyslipidaemia was documented in 153 recipients (58%) and was significantly more prevalent among recipients developing PGD (45 vs 108, P < 0.013). Despite various underlying pulmonary pathologies, higher triglyceride (TG) levels (1.41 ± 0.78 vs 1.16 ± 0.78, P < 0.012), lower high-density lipoprotein-cholesterol (HDL-C) concentrations (1.24 ± 0.55 vs 1.57 ± 0.71, P < 0.0005) and higher cholesterol/HDL-C values (3.80 ± 2.02 vs 3.00 ± 0.92, P < 0.0005) were associated with a lower incidence of PGD. Patients with PGD had significantly longer ischaemic time (350 ± 89 vs 322 ± 91, P = 0.017) and higher BMI (23 ± 5 vs 21 ± 4.4, P < 0.007). CONCLUSION: Dyslipidaemia seems to be an independent risk factor for PGD after lung transplantation: low circulating levels of HDL-C and hypertriglyceridaemia increase the incidence of PGD. Even if HDL-C levels are difficult to alter today, triglyceride and cholesterol levels can be addressed therapeutically and may have a positive influence on the development of PGD

Public perception of drinking water safety in South Africa 2002-2009: a repeated cross-sectional study

Background: In low and middle income countries, public perceptions of drinking water safety are relevant to promotion of household water treatment and to household choices over drinking water sources. However, most studies of this topic have been crosssectional and not considered temporal variation in drinking water safety perceptions. Theobjective of this study is to explore trends in perceived drinking water safety in South Africa and its association with disease outbreaks, water supply and householdcharacteristics.Methods: This repeated cross-sectional study draws on General Household Surveys from 2002-2009, a series of annual nationally representative surveys of South African households, which include a question about perceived drinking water safety. Trends in responses to this question were examined from 2002-2009 in relation to reported choleracases. The relationship between perceived drinking water safety and organoleptic qualities of drinking water, supply characteristics, and socio-economic and demographichousehold characteristics was explored in 2002 and 2008 using hierarchical stepwise logistic regression.Results: The results suggest that perceived drinking water safety has remained relatively stable over time in South Africa, once the expansion of improved supplies is controlled for. A large cholera outbreak in 2000-02 had no apparent effect on public perception of drinking water safety in 2002. Perceived drinking water safety is primarily related to water taste, odour, and clarity rather than socio-economic or demographic characteristics.Conclusion: This suggest that household perceptions of drinking water safety in South Africa follow similar patterns to those observed in studies in developed countries. The stability over time in public perception of drinking water safety is particularly surprising,given the large cholera outbreak that took place at the start of this period

Differential effects of dopamine signalling on long-term memory formation and consolidation in rodent brain

BACKGROUND: Using auditory discrimination learning in gerbils, we have previously shown that activation of auditory-cortical D1/D5 dopamine receptors facilitates mTOR-mediated, protein synthesis-dependent mechanisms of memory consolidation and anterograde memory formation. To understand molecular mechanisms of this facilitatory effect, we tested the impact of local pharmacological activation of different D1/D5 dopamine receptor signalling modes in the auditory cortex. To this end, protein patterns in soluble and synaptic protein-enriched fractions from cortical, hippocampal and striatal brain regions of ligand- and vehicle-treated gerbils were analysed by 2D gel electrophoresis and mass spectrometry 24 h after intervention. RESULTS: After auditory-cortical injection of SKF38393 – a D1/D5 dopamine receptor-selective agonist reported to activate the downstream effectors adenylyl cyclase and phospholipase C – prominent proteomic alterations compared to vehicle-treated controls appeared in the auditory cortex, striatum, and hippocampus, whereas only minor changes were detectable in the frontal cortex. In contrast, auditory-cortical injection of SKF83959 – a D1/D5 agonist reported to preferentially stimulate phospholipase C – induced pronounced changes in the frontal cortex. At the molecular level, we detected altered regulation of cytoskeletal and scaffolding proteins, changes in proteins with functions in energy metabolism, local protein synthesis, and synaptic signalling. Interestingly, abundance and/or subcellular localisation of the predominantly presynaptic protein α-synuclein displayed dopaminergic regulation. To assess the role of α-synuclein for dopaminergic mechanisms of memory modulation, we tested the impact of post-conditioning systemic pharmacological activation of different D1/D5 dopamine receptor signalling modes on auditory discrimination learning in α-synuclein-mutant mice. In C57BL/6JOlaHsd mice, bearing a spontaneous deletion of the α-synuclein-encoding gene, but not in the related substrains C57BL/6JCrl and C57BL/6JRccHsd, adenylyl cyclase-mediated signalling affected acquisition rates over future learning episodes, whereas phospholipase C-mediated signalling affected final memory performance. CONCLUSIONS: Dopamine signalling modes via D1/D5 receptors in the auditory cortex differentially impact protein profiles related to rearrangement of cytomatrices, energy metabolism, and synaptic neurotransmission in cortical, hippocampal, and basal brain structures. Altered dopamine neurotransmission in α-synuclein-deficient mice revealed that distinct D1/D5 receptor signalling modes may control different aspects of memory consolidation