Neuroimaging of rapid eye movement sleep behavior disorder and its relation to Parkinson's disease

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by polysomnography-confirmed REM sleep without atonia and dream-enacting behaviors. This disorder is considered a prodromal syndrome of alpha-synucleinopathies like Parkinson's disease (PD), where it affects more than 50% of PD patients. The underlying pathology of RBD has been generally understood to involve the pontine nuclei within the brainstem. However, the complete pathophysiology beyond the brainstem remains unclear as does its relationship with PD pathology. Therefore, this review aims to survey the neuroimaging literature involving PET, SPECT, and MR imaging techniques to provide an updated understanding of the neuro-chemical, structural, and functional changes in both RBD and PD patients comorbid with RBD. This review found neuroimaging evidence that indicate alterations to the dopaminergic and cholinergic system, blood perfusion, and glucose metabolism in both RBD patients and PD patients with RBD. Beyond the brainstem, structural and functional changes were found to involve the nigrostriatal system, limbic system, and the cortex-suggesting that RBD is a multi-systemic neurodegenerative process. Future investigations are encouraged to follow RBD patients longitudinally using multimodal imaging techniques to enhance our understanding of this parasomnia disorder. Uncovering which individuals are most likely to develop an alpha-synuclein disorder in the prodromal phase will improve patient outcomes and potentially aid in the development of novel treatments for patients affected by RBD

A Methodological Perspective on Genetic Risk Prediction Studies in Type 2 Diabetes: Recommendations for Future Research

Fueled by the successes of genome-wide association studies, numerous studies have investigated the predictive ability of genetic risk models in type 2 diabetes. In this paper, we review these studies from a methodological perspective, focusing on the variables included in the risk models as well as the study designs and populations investigated. We argue and show that differences in study design and characteristics of the study population have an impact on the observed predictive ability of risk models. This observation emphasizes that genetic risk prediction studies should be conducted in those populations in which the prediction models will ultimately be applied, if proven useful. Of all genetic risk prediction studies to date, only a few were conducted in populations that might be relevant for targeting preventive interventions

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Meta-analyses of genome-wide association studies for postpartum depression

Objective: Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD. Method: Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)–based heritability (), 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system. Results: No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD. Conclusions: While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone)

The Nurse Workload in Work with Geriatric Patients in Social Care Centres

Maģistra darba tēma ir „Māsu noslodze darbā ar geriatriskiem pacientiem sociālās aprūpes iestādēs”. Geriatrija ir zinātne par vecu cilvēku slimībām, to ārstēšanu un aprūpi. Geriatrijas aizsācēji ir I .L. Nascher un M. Warrner. Visā pasaulē noris sabiedrības novecošana. Pēc Eiropas Komisijas datiem, tuvākajās desmitgadēs iedzīvotāju skaits pieaugs par 2 miljoniem cilvēku gadā. Novecošana ,savukārt, ir cieši saistīta ar sociālās aprūpes pakalpojumiem. Darbs sastāv no 6 nodaļām un 12 apakšnodaļām. Tas ietver 2 tabulas, 23 attēlus un ir balstīts uz 75 literatūras avotiem. Pētījuma mērķis ir noskaidrot māsu noslodzi darbā ar geriatriskiem pacientiem sociālās aprūpes iestādēs. Pētniecības uzdevumi ir literatūras avotu izpēte, pētījuma anketas un novērošanas protokola izstrāde un analīze. Pētījums veikts 6 sociālās aprūpes iestādēs un aptvēra 38 respondentus. Darbā izmantota kvantitatīvā un kvalitatīvā pētījuma metode. Pirmā nodaļa sniedz ieskatu geriatrijas pirmsākumos un tās attīstībā visā pasaulē. Otrā nodaļa raksturo geriatriju kā zinātni un dod pārskatu par sabiedrības novecošanas tendencēm, kā arī par geriatrisko pacientu veselības problēmām. Trešā nodaļa raksturo māsu lomu geriatrisku pacientu aprūpē māszinību teorijās. Ceturtā nodaļa sniedz pārskatu par sociālās aprūpes centru darbu un māsu noslodzi. Piektā nodaļa sniedz pārskatu par pētījuma metodoloģiju. Sestā nodaļa saistīta ar pētniecības darbu – informācijas datu analīzi. Darba autore nonāca pie secinājuma, ka māsu noslodzi SAC ir pārāk intensīva un neadekvāta attiecībā pret uzticētajiem pienākumiem un geriatrisko pacientu skaitu.The theme of the master’s thesis is “The nurse workload in work with geriatric patients at social care centres”. Geriatry is a science about the old people deseases, theraphy and healthcare. Geriatrics was started by I. L. Nascher and M. Warren. People all around the world have been ageing. According to EC statictics, the number of people will increase in coming decades by 2 million people a year. Ageing is closely linked with the services of social care centers. The work consists of 6 units and 12 subunits. It includes 2 tables, 23 pictures and is based on 75 bibliographic sources. The aim of this work is to find out the nurse workload in work with geriatric patients at social care centres. The tasks of the research is to estimate sources, the questionair and the minutes to compile and analyse the results of the research. The research was carried outin 6 social care centers and included 38 respondents. The research is based on the qualitative and the quantitative methods. The 1 st unit gives insight in the pre-history of geriatrics and its development in the world. The 2 nd unit describes geriatrics as science and includes the survey about the ageing of the society and describes the health problems of geriatric patients. The 3 rd unit describethe role of the nurse in nursing theories at work with geriatric patients. The 4 th unit includes the survey about social care centres and the role of the geriatric nurse in it. The 5 th unit deals with nursing theories. The 6 th unit deals with the research itself the author came to the conclusion that the nurse workload in social care centers is too intensive and not adequate as to the number of geriatric patients and the duties she has to cope with

Modeling of EGR Mixing in an engine intake manifold using LES

We investigate the mixing process of exhaust gases with fresh air in Internal Combustion Engines (ICE). For this purpose, the flow in an inlet manifold of a six-cylinder heavy-duty Diesel engine is computed using compressible Large Eddy Simulations (LES). The Exhaust Gas Recirculation (EGR) concentration is modeled as a passive scalar. The results are validated by on-engine measurements of the EGR concentration using CO2-probes. The boundary conditions for the highly pulsating flow are taken partly from one-dimensional simulations, partly from pressure measurements on the engine. In order to assess the sensitivity to the boundary conditions, changes are applied to the base-line case. The mixing quality is evaluated in terms of cylinder-to-cylinder distribution and the spatial RMS over the outlet cross-sections. Different averaging techniques are applied. It was found that the temporal and spatial EGR distribution is different among the cylinders. The EGR distribution within the cylinder inlet is non-uniform. These factors imply that one should not use a time-averaged EGR value as indicator for the EGR content. Furthermore, it was found that the flow pulsations at the EGR inlet have a large influence on the EGR distribution. By comparing the LES results with measurements, it was shown that LES gives a better and deeper insight into the mixing in such turbulent, pulsating flow situations.QC 20130207</p

VMAT2 availability in Parkinson's disease with probable REM sleep behaviour disorder

REM sleep behaviour disorder (RBD) can be an early non-motor symptom of Parkinson's disease (PD) with pathology involving mainly the pontine nuclei. Beyond the brainstem, it is unclear if RBD patients comorbid with PD have more affected striatal dopamine denervation compared to PD patients unaffected by RBD (PD-RBD−). To elucidate this, we evaluated the availability of vesicular monoamine transporter 2 (VMAT2), an index of nigrostriatal dopamine innervation, in 15 PD patients with probable RBD (PD-RBD+), 15 PD-RBD−, and 15 age-matched healthy controls (HC) using [11C]DTBZ PET imaging. This technique measured VMAT2 availability within striatal regions of interest (ROI). A mixed effect model was used to compare the radioligand binding of VMAT2 between the three groups for each striatal ROI, while co-varying for sex, cognitive function and depression scores. Multiple regressions were also computed to predict clinical measures from group condition and VMAT2 binding within all ROIs explored. We observed a significant main effect of group condition on VMAT2 availability within the caudate, putamen, ventral striatum, globus pallidus, substantia nigra, and subthalamus. Specifically, our results revealed that PD-RBD+ had lower VMAT2 availability compared to HC in all these regions except for the subthalamus and substantia nigra, while PD-RBD− was significantly lower than HC in all these regions. PD-RBD− showed a negative relationship between motor severity and VMAT2 availability within the left caudate. Our findings reflect that both PD patient subgroups had similar denervation within the nigrostriatal pathway. There were no significant interactions detected between radioligand binding and clinical scores in PD-RBD+. Taken together, VMAT2 and striatal dopamine denervation in general may not be a significant contributor to the pathophysiology of RBD in PD patients. Future studies are encouraged to explore other underlying neural chemistry mechanisms contributing to RBD in PD patients

Personalizing health care: feasibility and future implications

Considerable variety in how patients respond to treatments, driven by differences in their geno- and/ or phenotypes, calls for a more tailored approach. This is already happening, and will accelerate with developments in personalized medicine. However, its promise has not always translated into improvements in patient care due to the complexities involved. There are also concerns that advice for tests has been reversed, current tests can be costly, there is fragmentation of funding of care, and companies may seek high prices for new targeted drugs. There is a need to integrate current knowledge from a payer’s perspective to provide future guidance. Multiple findings including general considerations; influence of pharmacogenomics on response and toxicity of drug therapies; value of biomarker tests; limitations and costs of tests; and potentially high acquisition costs of new targeted therapies help to give guidance on potential ways forward for all stakeholder groups. Overall, personalized medicine has the potential to revolutionize care. However, current challenges and concerns need to be addressed to enhance its uptake and funding to benefit patients

Neutrophil extracellular trap-microparticle complexes trigger neutrophil recruitment via high-mobility group protein 1 (HMGB1)-toll-like receptors(TLR2)/TLR4 signalling

Background and Purpose: Recent data suggest that neutrophil extracellular traps (NETs) form aggregates with microparticles (MPs) upon activation of neutrophils although the functional role of NET-MP complexes remain elusive. The objective of this study was to examine the role of NET-MP aggregates in leukocyte recruitment in vivo. Experimental Approach: PMA stimulation of murine bone marrow neutrophils generated NET-MP complexes and pretreatment with caspase and calpain inhibitors resulted in the formation of NETs depleted of MPs. Leukocyte–endothelium interactions were studied by using intravital microscopy of the mouse cremaster microcirculation. Key Results: Intrascrotal injection of NET-MP aggregates dose-dependently increased leukocyte recruitment. In contrast, leukocyte responses were markedly reduced after administration of NETs depleted of MPs. Neutrophil depletion abolished intravascular and extravascular leukocytes in response to challenge with NET-MP complexes. Electron microscopy revealed that NET-associated MPs express HMGB1. Notably, immunoneutralization of HMGB1 markedly decreased NET-MP complex-induced neutrophil accumulation. Moreover, inhibition of TLR2 and TLR4 significantly reduced neutrophil recruitment in response to NET-MP aggregates. Conclusions and Implications: These data show that NET-MP complexes are potent inducers of neutrophil recruitment, which is dependent on HMGB1 expressed on MPs and mediated via TLR2 and TLR4. Blocking MP binding to NETs or downstream inhibition of the HMGB1-TLR2/TLR4 axis might provide useful targets to attenuating NET-dependent tissue damage in acute inflammation