Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 821
Filtrar
1.
J Vis Exp ; (150)2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31498302

RESUMO

Biofilms are a most successful microbial lifestyle and prevail in a multitude of environmental and engineered settings. Understanding biofilm morphogenesis, that is the structural diversification of biofilms during community assembly, represents a remarkable challenge across spatial and temporal scales. Here, we present an automated biofilm imaging system based on optical coherence tomography (OCT). OCT is an emerging imaging technique in biofilm research. However, the amount of data that currently can be acquired and processed hampers the statistical inference of large scale patterns in biofilm morphology. The automated OCT imaging system allows covering large spatial and extended temporal scales of biofilm growth. It combines a commercially available OCT system with a robotic positioning platform and a suite of software solutions to control the positioning of the OCT scanning probe, as well as the acquisition and processing of 3D biofilm imaging datasets. This setup allows the in situ and non-invasive automated monitoring of biofilm development and may be further developed to couple OCT imaging with macrophotography and microsensor profiling.

2.
Pediatr Res ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31499516

RESUMO

BACKGROUND: Eye-tracking devices help to understand provider behavior during medical tasks. The aim of this study was to assess participants' gaze behavior and usability of eye-tracking glasses during airway management in a simulated neonatal resuscitation. METHODS: This study was an observational simulation-based study. The team member assigned to airway management wore head-mounted eye-tracking glasses. Main outcome measures were airway providers' gaze, dwell time (total amount of time a participant fixates), and usability of eye-tracking glasses. RESULTS: Data from 13 participants were included. There were significant differences in dwell time (total amount of time a participant fixates certain areas of interest) during the scenario (p < 0.001), with participants spending twice as much time on the newborn and instruments as on the monitor and other staff. Participants spent about 25% more time focusing on another provider while the provider was inserting the umbilical vein catheter than in all other times of interest (intervals of time with meaningful events) (p = 0.04). The use of the glasses was perceived easy and not disturbing. CONCLUSIONS: Eye-tracking glasses enhance our understanding of providers' gaze and perspective during simulated neonatal airway management. Future studies will better characterize the ideal use in real situations.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31420340

RESUMO

Ca. Nitrosotenuis uzonensis is the only cultured moderately thermophilic member of the thaumarchaeotal order Nitrosopumilales (NP) that contains many mesophilic marine strains. We examined its membrane lipid composition at different growth temperatures (37, 46 and 50 °C). Its lipids were all membrane-spanning glycerol dialkyl glycerol tetraethers (GDGTs), with 0 to 4 cyclopentane moieties. Crenarchaeol (cren), the characteristic thaumarchaeotal GDGT, and its isomer (cren') were present in high abundance (30-70 %). The GDGT polar headgroups were mono-, di- and trihexoses and hexose/phosphohexose. The ratio of glycolipid to phospholipid GDGTs was highest in the cultures grown at 50 °C. With increasing growth temperature, the relative contribution of cren and cren' increased, while GDGT-0 to GDGT-4 (including isomers) decreased. TEX86 (tetraether index of tetraethers consisting of 86 carbons)-derived temperatures were much lower than the actual growth temperatures, further demonstrating that TEX86 does not accurately reflect the membrane lipid adaptation of thermophilic Thaumarchaeota. As temperature increased, specific GDGTs changed relative to their isomers, possibly representing temperature adaption-induced changes in cyclopentane ring stereochemistry. Comparison of a wide range of thaumarcheotal core lipid compositions revealed the Ca. N. uzonensis cultures clustered separately from other members of the NP order and the Nitrososphaerales (NS) order. While phylogeny generally seems to have a strong influence on GDGT distribution, our analysis of Ca. Nitrosotenuis uzonensis demonstrates that its terrestrial, higher temperature niche has led to a lipid composition that clearly differentiates it from other NP members and that this difference is mostly driven by its high cren' content.Importance For Thaumarchaeota the ratio of their Glycerol Dialkyl Glycerol Tetraether (GDGT) lipids depends on growth temperature, a premise that forms the basis of the widely applied TEX86 paleotemperature proxy. A thorough understanding of which GDGTs are produced by which Thaumarchaeota and what the effect of temperature is on their GDGT composition is essential for constraining the TEX86 proxy. Ca. Nitrosotenuis uzonensis is a moderately thermophilic Thaumarchaeote enriched from a thermal spring, setting it apart in its environmental niche from the other marine mesophilic members of its order. Indeed, we found that the GDGT composition of Ca. N. uzonensis cultures was distinct from other members of its order and was more similar to other thermophilic, terrestrial Thaumarchaeota. This suggests that while phylogeny has a strong influence on GDGT distribution, the environmental niche that a Thaumarchaeote inhabits also shapes its GDGT composition.

4.
ISME J ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462715

RESUMO

Thaumarchaeota are responsible for a significant fraction of ammonia oxidation in the oceans and in soils that range from alkaline to acidic. However, the adaptive mechanisms underpinning their habitat expansion remain poorly understood. Here we show that expansion into acidic soils and the high pressures of the hadopelagic zone of the oceans is tightly linked to the acquisition of a variant of the energy-yielding ATPases via horizontal transfer. Whereas the ATPase genealogy of neutrophilic Thaumarchaeota is congruent with their organismal genealogy inferred from concatenated conserved proteins, a common clade of V-type ATPases unites phylogenetically distinct clades of acidophilic/acid-tolerant and piezophilic/piezotolerant species. A presumptive function of pumping cytoplasmic protons at low pH is consistent with the experimentally observed increased expression of the V-ATPase in an acid-tolerant thaumarchaeote at low pH. Consistently, heterologous expression of the thaumarchaeotal V-ATPase significantly increased the growth rate of E. coli at low pH. Its adaptive significance to growth in ocean trenches may relate to pressure-related changes in membrane structure in which this complex molecular machine must function. Together, our findings reveal that the habitat expansion of Thaumarchaeota is tightly correlated with extensive horizontal transfer of atp operons.

5.
Alzheimers Res Ther ; 11(1): 66, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31366409

RESUMO

BACKGROUND: Subjective cognitive decline (SCD) has been proposed as a pre-MCI at-risk condition of Alzheimer's disease (AD). Current research is focusing on a refined assessment of specific SCD features associated with increased risk for AD, as proposed in the SCD-plus criteria. We developed a structured interview (SCD-I) for the assessment of these features and tested their relationship with AD biomarkers. METHODS: We analyzed data of 205 cognitively normal participants of the DELCODE study (mean age = 68.9 years; 52% female) with available CSF AD biomarkers (Aß-42, p-Tau181, Aß-42/Tau ratio, total Tau). For each of five cognitive domains (including memory, language, attention, planning, others), a study physician asked participants about the following SCD-plus features: the presence of subjective decline, associated worries, onset of SCD, feeling of worse performance than others of the same age group, and informant confirmation. We compared AD biomarkers of subjects endorsing each of these questions with those who did not, controlling for age. SCD was also quantified by two summary scores: the number of fulfilled SCD-plus features, and the number of domains with experienced decline. Covariate-adjusted linear regression analyses were used to test whether these SCD scores predicted abnormality in AD biomarkers. RESULTS: Lower Aß-42 levels were associated with a reported decline in memory and language abilities, and with the following SCD-plus features: onset of subjective decline within 5 years, confirmation of cognitive decline by an informant, and decline-related worries. Furthermore, both quantitative SCD scores were associated with lower Aß42 and lower Aß42/Tau ratio, but not with total Tau or p-Tau181. CONCLUSIONS: Findings support the usefulness of a criterion-based interview approach to assess and quantify SCD in the context of AD and validate the current SCD-plus features as predictors of AD pathology. While some features seem to be more closely associated with AD biomarkers than others, aggregated scores over several SCD-plus features or SCD domains may be the best predictors of AD pathology.

6.
Traffic Inj Prev ; 20(sup1): S139-S145, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31381432

RESUMO

Objective: With the overall goal to harmonize prospective effectiveness assessment of active safety systems, the specific objective of this study is to identify and evaluate sources of variation in virtual precrash simulations and to suggest topics for harmonization resulting in increased comparability and thus trustworthiness of virtual simulation-based prospective effectiveness assessment. Methods: A round-robin assessment of the effectiveness of advanced driver assistance systems was performed using an array of state-of-the-art virtual simulation tools on a set of standard test cases. The results were analyzed to examine reasons for deviations in order to identify and assess aspects that need to be harmonized and standardized. Deviations between results calculated by independent engineering teams using their own tools should be minimized if the research question is precisely formulated regarding input data, models, and postprocessing steps. Results: Two groups of sources of variations were identified; one group (mostly related to the implementation of the system under test) can be eliminated by using a more accurately formulated research question, whereas the other group highlights further harmonization needs because it addresses specific differences in simulation tool setups. Time-to-collision calculations, vehicle dynamics, especially braking behavior, and hit-point position specification were found to be the main sources of variation. Conclusions: The study identified variations that can arise from the use of different simulation setups in assessment of the effectiveness of active safety systems. The research presented is a first of its kind and provides significant input to the overall goal of harmonization by identifying specific items for standardization. Future activities aim at further specification of methods for prospective assessments of the effectiveness of active safety, which will enhance comparability and trustworthiness in this kind of studies and thus contribute to increased traffic safety.

7.
Aggress Behav ; 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31418876

RESUMO

Two studies tested whether attributions of hostile intent (AHI) and anger for ambiguous child behaviors uniquely predict parents' harsh verbal discipline (HVD) and harsh physical discipline (HPD) or whether AHI only predicts harsh discipline when AHI occurs in conjunction with anger, as suggested by the Integrated Cognitive Model of general aggression (Wilkowski & Robinson, 2010, J. Pers., 78, 9-38). Replicating previous studies, the expected positive bivariate relationships between AHI, anger, HVD, and HPD were found in Study 1 (N = 493). However, when AHI, anger, and the AHI by anger interaction were considered simultaneously, patterns of prediction varied by discipline type. For HVD, high levels of AHI, high levels of anger, and the AHI by anger interaction (at high levels of AHI and anger) each were significant predictors. For HPD, low levels of AHI, high levels of anger, and the AHI by anger interaction (at high levels of AHI and anger) were significant predictors, suggesting a possible suppressor effect for AHI. These results were replicated in Study 2 ( N = 503). Thus, there was support for the contention that AHI only predicts harsh discipline when AHI occurs in conjunction with anger with respect to HPD but this was not the case for HVD. Since AHI suppressor effects were observed for HPD in two large sample studies, variables that may account for the AHI suppressor effects and the need for testing more complex interactive predictive models of harsh parenting behaviors are discussed.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31427514

RESUMO

Cable bacteria of the family Desulfobulbaceae form centimeter-long filaments comprising thousands of cells. They occur worldwide in the surface of aquatic sediments, where they connect sulfide oxidation with oxygen or nitrate reduction via long-distance electron transport. In the absence of pure cultures, we used single-filament genomics and metagenomics to retrieve draft genomes of 3 marine Candidatus Electrothrix and 1 freshwater Ca. Electronema species. These genomes contain >50% unknown genes but still share their core genomic makeup with sulfate-reducing and sulfur-disproportionating Desulfobulbaceae, with few core genes lost and 212 unique genes (from 197 gene families) conserved among cable bacteria. Last common ancestor analysis indicates gene divergence and lateral gene transfer as equally important origins of these unique genes. With support from metaproteomics of a Ca. Electronema enrichment, the genomes suggest that cable bacteria oxidize sulfide by reversing the canonical sulfate reduction pathway and fix CO2 using the Wood-Ljungdahl pathway. Cable bacteria show limited organotrophic potential, may assimilate smaller organic acids and alcohols, fix N2, and synthesize polyphosphates and polyglucose as storage compounds; several of these traits were confirmed by cell-level experimental analyses. We propose a model for electron flow from sulfide to oxygen that involves periplasmic cytochromes, yet-unidentified conductive periplasmic fibers, and periplasmic oxygen reduction. This model proposes that an active cable bacterium gains energy in the anodic, sulfide-oxidizing cells, whereas cells in the oxic zone flare off electrons through intense cathodic oxygen respiration without energy conservation; this peculiar form of multicellularity seems unparalleled in the microbial world.

9.
J Atten Disord ; : 1087054719864656, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31364437

RESUMO

Objective: The objective of this study was to assess the MOXO-d-CPT utility in detecting feigned ADHD and establish cutoffs with adequate specificity and sensitivity. Method: The study had two phases. First, using a prospective design, healthy adults who simulated ADHD were compared with healthy controls and ADHD patients who performed the tasks to the best of their ability (n = 47 per group). Participants performed the MOXO-d-CPT and an established performance validity test (PVT). Second, the MOXO-d-CPT classification accuracy, employed in Phase 1, was retrospectively compared with archival data of 47 ADHD patients and age-matched healthy controls. Results: Simulators performed significantly worse on all MOXO-d-CPT indices than healthy controls and ADHD patients. Three MOXO-d-CPT indices (attention, hyperactivity, impulsivity) and a scale combining these indices showed adequate discriminative capacity. Conclusion: The MOXO-d-CPT showed promise for the detection of feigned ADHD and, pending replication, can be employed for this aim in clinical practice and ADHD research.

10.
Aging Clin Exp Res ; 2019 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31422564

RESUMO

BACKGROUND: Hospitalization is a key driver of health care costs. Thus far, there are only a few longitudinal studies investigating whether changes in explanatory variables lead to hospitalization. Moreover, these longitudinal studies did not focus on individuals in highest age. AIM: The purpose of the current study was to examine the correlates of hospitalization among the oldest old in Germany longitudinally. METHODS: A multicenter prospective cohort study ["Study on Needs, health service use, costs and health-related quality of life in a large sample of oldest-old primary care patients (85+)", AgeQualiDe]. Primary care patients ≥ 85 years took part [n = 861 at follow-up (FU) 7, average age of 89.0 years; 85-100 years]. Two waves were used. Hospitalization in the last 6 months was used as outcome measure. Well-established scales were used to quantify the independent variables such as Instrumental Activities of Daily Living Scale, Global Deterioration Scale or Geriatric Depression Scale. RESULTS: Logistic random effects regressions showed that the probability of hospitalization in the preceding 6 months significantly increased with increases in the social network, more depressive symptoms, functional decline, and increase in chronic conditions, whereas it was not significantly associated with age, sex, marital status, education, and cognitive impairment. Social networks moderate the relationship between functional decline and hospitalization. DISCUSSION: The results of the present longitudinal study emphasize the association of depressive symptoms, functional decline, more social networks, and chronic conditions with hospitalization among the oldest old. CONCLUSIONS: Treatments with the aim to reduce or postpone these factors might also help to reduce hospitalization.

11.
Stud Health Technol Inform ; 264: 1580-1581, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438241

RESUMO

Clinical Decision Support Systems (CDSS) are promising to support physicians in finding the right diagnosis of patients with rare diseases (RD). The MIRACUM consortium, which includes ten university hospitals in Germany, will establish a diagnosis support system for RD. This system conducts a similarity analysis on distributed clinical data with the aim to identify similar patient cases at each MIRACUM site to offer the physician a hint to a possible diagnosis.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Alemanha , Hospitais Universitários , Humanos , Médicos
12.
Environ Microbiol ; 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31271506

RESUMO

Marine sponges represent one of the few eukaryotic groups that frequently harbour symbiotic members of the Thaumarchaeota, which are important chemoautotrophic ammonia-oxidizers in many environments. However, in most studies, direct demonstration of ammonia-oxidation by these archaea within sponges is lacking, and little is known about sponge-specific adaptations of ammonia-oxidizing archaea (AOA). Here, we characterized the thaumarchaeal symbiont of the marine sponge Ianthella basta using metaproteogenomics, fluorescence in situ hybridization, qPCR and isotope-based functional assays. 'Candidatus Nitrosospongia ianthellae' is only distantly related to cultured AOA. It is an abundant symbiont that is solely responsible for nitrite formation from ammonia in I. basta that surprisingly does not harbour nitrite-oxidizing microbes. Furthermore, this AOA is equipped with an expanded set of extracellular subtilisin-like proteases, a metalloprotease unique among archaea, as well as a putative branched-chain amino acid ABC transporter. This repertoire is strongly indicative of a mixotrophic lifestyle and is (with slight variations) also found in other sponge-associated, but not in free-living AOA. We predict that this feature as well as an expanded and unique set of secreted serpins (protease inhibitors), a unique array of eukaryotic-like proteins, and a DNA-phosporothioation system, represent important adaptations of AOA to life within these ancient filter-feeding animals.

13.
J Affect Disord ; 256: 650-657, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31301630

RESUMO

BACKGROUND: Old age is accompanied by a higher risk of losing a spouse. This study aims to longitudinally investigate the effect of widowhood on depression severity with a special focus on sex differences. We examine depression before and after widowhood in men and women separately to investigate which sex is at greater risk after losing a spouse. METHODS: Data came from the AgeDifferent.de platform, which includes three pooled old age cohort studies. In order to examine factors associated with depression over time, we applied a linear hybrid mixed-effects regression model for the overall sample and analysed additional separate models for men and women. RESULTS: Of 2470 respondents (mean age at baseline 79.2 (SD 3.64) years), 1256 were men. In total, 209 men and 332 women experienced spousal bereavement after baseline. In general, both sexes showed higher depression severity after widowhood. However, there were significant sex differences. Widowed men were more prone to subsequent depression than widowed women. In terms of depression severity, widowed men differed significantly compared to non-widowed men; however, this was not the case for women. LIMITATION: We harmonized three cohort studies which used different measurement scales for depression and different recruitment procedures. CONCLUSION: Our study showed that although both genders suffer from losing a spouse, men are more prone to subsequently develop depressive symptoms. Raising the awareness among practitioners for sex-specific differences as well as developing tailored interventions for both widowed men and women should be considered.

14.
Environ Sci Technol ; 53(15): 8695-8705, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31294971

RESUMO

The recently discovered complete ammonia-oxidizing (comammox) bacteria occur in various environments, including wastewater treatment plants. To better understand their role in micropollutant biotransformation in comparison with ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA), we investigated the biotransformation capability of Nitrospira inopinata (the only comammox isolate) for 17 micropollutants. Asulam, fenhexamid, mianserin, and ranitidine were biotransformed by N. inopinata, Nitrososphaera gargensis (AOA), and Nitrosomonas nitrosa Nm90 (AOB). More distinctively, carbendazim, a benzimidazole fungicide, was exclusively biotransformed by N. inopinata. The biotransformation of carbendazim only occurred when N. inopinata was supplied with ammonia but not nitrite as the energy source. The exclusive biotransformation of carbendazim by N. inopinata was likely enabled by an enhanced substrate promiscuity of its unique AMO and its much higher substrate (for ammonia) affinity compared with the other two ammonia oxidizers. One major plausible transformation product (TP) of carbendazim is a hydroxylated form at the aromatic ring, which is consistent with the function of AMO. These findings provide fundamental knowledge on the micropollutant degradation potential of a comammox bacterium to better understand the fate of micropollutants in nitrifying environments.

15.
ISME J ; 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227816

RESUMO

Nitrous oxide (N2O) is a key climate change gas and nitrifying microbes living in terrestrial ecosystems contribute significantly to its formation. Many soils are acidic and global change will cause acidification of aquatic and terrestrial ecosystems, but the effect of decreasing pH on N2O formation by nitrifiers is poorly understood. Here, we used isotope-ratio mass spectrometry to investigate the effect of acidification on production of N2O by pure cultures of two ammonia-oxidizing archaea (AOA; Nitrosocosmicus oleophilus and Nitrosotenuis chungbukensis) and an ammonia-oxidizing bacterium (AOB; Nitrosomonas europaea). For all three strains acidification led to increased emission of N2O. However, changes of 15N site preference (SP) values within the N2O molecule (as indicators of pathways for N2O formation), caused by decreasing pH, were highly different between the tested AOA and AOB. While acidification decreased the SP value in the AOB strain, SP values increased to a maximum value of 29‰ in N. oleophilus. In addition, 15N-nitrite tracer experiments showed that acidification boosted nitrite transformation into N2O in all strains, but the incorporation rate was different for each ammonia oxidizer. Unexpectedly, for N. oleophilus more than 50% of the N2O produced at pH 5.5 had both nitrogen atoms from nitrite and we demonstrated that under these conditions expression of a putative cytochrome P450 NO reductase is strongly upregulated. Collectively, our results indicate that N. oleophilus might be able to enzymatically denitrify nitrite to N2O at low pH.

16.
J Neurol ; 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227891

RESUMO

INTRODUCTION: Subjective cognitive decline (SCD) can represent a preclinical stage of Alzheimer's disease. Diffusion tensor imaging (DTI) could aid an early diagnosis, yet only few monocentric DTI studies in SCD have been conducted, reporting heterogeneous results. We investigated microstructural changes in SCD in a larger, multicentric cohort. METHODS: 271 participants with SCD, mild cognitive impairment (MCI) or Alzheimer's dementia (AD) and healthy controls (CON) were included, recruited prospectively at nine centers of the observational DELCODE study. DTI was acquired using identical protocols. Using voxel-based analyses, we investigated fractional anisotropy (FA), mean diffusivity (MD) and mode (MO) in the white matter (WM). Discrimination accuracy was determined by cross-validated elastic-net penalized regression. Center effects were explored using variance analyses. RESULTS: MO and FA were lower in SCD compared to CON in several anterior and posterior WM regions, including the anterior corona radiata, superior and inferior longitudinal fasciculus, cingulum and splenium of the corpus callosum (p < 0.01, uncorrected). MD was higher in the superior and inferior longitudinal fasciculus, cingulum and superior corona radiata (p < 0.01, uncorrected). The cross-validated accuracy for discriminating SCD from CON was 67% (p < 0.01). As expected, the AD and MCI groups had higher MD and lower FA and MO in extensive regions, including the corpus callosum and temporal brain regions. Within these regions, center accounted for 3-15% of the variance. CONCLUSIONS: DTI revealed subtle WM alterations in SCD that were intermediate between those in MCI and CON and may be useful to detect individuals with an increased risk for AD in clinical studies.

17.
Geriatr Gerontol Int ; 19(8): 705-710, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31237101

RESUMO

AIM: The purpose of this study was to investigate whether transpersonal trust (TPT) moderates the relationship between chronic conditions and general practitioner (GP) visits among the oldest old in Germany. METHODS: The multicenter prospective cohort Study on Needs, health service use, costs and health-related quality of life in a large sample of oldest old primary care patients (85+) (AgeQualiDe) was carried out. Individuals were recruited through GP offices at six study centers in Germany (follow-up wave 7). Primary care patients were aged ≥85 years (n = 861, mean age 89.0 years; range 85-100 years). The self-reported number of outpatient visits to the GP was used as the outcome measure. To explore religious and spiritual beliefs, the short form of the Transpersonal Trust scale was used. The presence or absence of 36 chronic conditions was recorded by the GP. RESULTS: Multiple Poisson regressions showed that GP visits were positively associated with the number of chronic conditions (incidence rate ratio 1.03, P < 0.05). TPT moderated the relationship between chronic conditions and GP visits (incidence rate ratio 1.01, P < 0.05). The association between chronic conditions and GP visits was significantly more pronounced when TPT was high. CONCLUSION: Our findings highlight the importance of TPT in the relationship between chronic conditions and GP visits. Future longitudinal studies are required to clarify this subject further. Geriatr Gerontol Int 2019; 19: 705-710.

18.
BMJ Open ; 9(6): e026604, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31230007

RESUMO

INTRODUCTION: More than 2 million individuals in the USA have an opioid use disorder (OUD). Methadone maintenance treatment is the gold standard of medication-based treatment for OUD, but high-dose methadone is associated with cardiotoxicity and respiratory complications, among other side effects. These adverse effects make enhancing the effectiveness of lower doses of methadone an attractive therapeutic goal. Long recognised for its capacity to enhance treatment outcomes for a wide range of neuropsychiatric disorders including pain, the placebo effect offers an as-yet untested avenue to such an enhancement. This approach is particularly compelling given that individuals with substance use disorder tend to have higher salience attribution and may thereby be more sensitive to placebo effects. Our study combines two promising clinical methodologies-conditioning/dose-extension and open-label placebo-to investigate whether placebo effects can increase the effective potency of methadone in treatment-seeking OUD patients. METHODS AND ANALYSIS: A total of 120 newly enrolled treatment-seeking OUD patients will be randomly assigned to one of two different groups: either methadone plus daily placebo dose-extension (PDE; treatment group) or methadone/treatment as usual (control). Participants will meet with study team members five times over the course of 3 months of treatment with methadone (baseline, 2 weeks, and 1, 2 and 3 months postbaseline). Throughout this study time period, methadone dosages will be adjusted by an addiction clinician blind to patient assignment, per standard clinical methods. The primary outcome is methadone dose at 3 months. Secondary outcomes include self-report of drug use; 3-month urine toxicology screen results; and treatment retention. Exploratory outcomes include several environmental as well as personality factors associated with OUD and with propensity to demonstrate a placebo effect. ETHICS AND DISSEMINATION: Human subjects oversight for this study is provided by the University of Maryland, Baltimore and University of Maryland, College Park Institutional Review Boards. Additionally, the study protocol is reviewed annually by an independent Data and Safety Monitoring Board. Study results will be disseminated via research conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT02941809.

19.
Sci Rep ; 9(1): 8933, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31222095

RESUMO

Biofilms are the natural form of life of the majority of microorganisms. These multispecies consortia are intensively studied not only for their effects on health and environment but also because they have an enormous potential as tools for biotechnological processes. Further exploration and exploitation of these complex systems will benefit from technical solutions that enable integrated, machine-assisted cultivation and analysis. We here introduce a microfluidic platform, where readily available microfluidic chips are connected by automated liquid handling with analysis instrumentation, such as fluorescence detection, microscopy, chromatography and optical coherence tomography. The system is operable under oxic and anoxic conditions, allowing for different gases and nutrients as feeding sources and it offers high spatiotemporal resolution in the analysis of metabolites and biofilm composition. We demonstrate the platform's performance by monitoring the productivity of biofilms as well as the spatial organization of two bacterial species in a co-culture, which is driven by chemical gradients along the microfluidic channel.

20.
Schizophr Bull ; 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31206164

RESUMO

BACKGROUND: Cognitive impairment is a clinically important feature of schizophrenia. Polygenic risk score (PRS) methods have demonstrated genetic overlap between schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), educational attainment (EA), and IQ, but very few studies have examined associations between these PRS and cognitive phenotypes within schizophrenia cases. METHODS: We combined genetic and cognitive data in 3034 schizophrenia cases from 11 samples using the general intelligence factor g as the primary measure of cognition. We used linear regression to examine the association between cognition and PRS for EA, IQ, schizophrenia, BD, and MDD. The results were then meta-analyzed across all samples. A genome-wide association studies (GWAS) of cognition was conducted in schizophrenia cases. RESULTS: PRS for both population IQ (P = 4.39 × 10-28) and EA (P = 1.27 × 10-26) were positively correlated with cognition in those with schizophrenia. In contrast, there was no association between cognition in schizophrenia cases and PRS for schizophrenia (P = .39), BD (P = .51), or MDD (P = .49). No individual variant approached genome-wide significance in the GWAS. CONCLUSIONS: Cognition in schizophrenia cases is more strongly associated with PRS that index cognitive traits in the general population than PRS for neuropsychiatric disorders. This suggests the mechanisms of cognitive variation within schizophrenia are at least partly independent from those that predispose to schizophrenia diagnosis itself. Our findings indicate that this cognitive variation arises at least in part due to genetic factors shared with cognitive performance in populations and is not solely due to illness or treatment-related factors, although our findings are consistent with important contributions from these factors.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA