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1.
J Alzheimers Dis ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31594223

RESUMO

Diffusion changes as determined by diffusion tensor imaging are potential indicators of microstructural lesions in people with mild cognitive impairment (MCI), prodromal Alzheimer's disease (AD), and AD dementia. Here we extended the scope of analysis toward subjective cognitive complaints as a pre-MCI at risk stage of AD. In a cohort of 271 participants of the prospective DELCODE study, including 93 healthy controls and 98 subjective cognitive decline (SCD), 45 MCI, and 35 AD dementia cases, we found reductions of fiber tract integrity in limbic and association fiber tracts in MCI and AD dementia compared with controls in a tract-based analysis (p < 0.05, family wise error corrected). In contrast, people with SCD showed spatially restricted white matter alterations only for the mode of anisotropy and only at an uncorrected level of significance. DTI parameters yielded a high cross-validated diagnostic accuracy of almost 80% for the clinical diagnosis of MCI and the discrimination of Aß positive MCI cases from Aß negative controls. In contrast, DTI parameters reached only random level accuracy for the discrimination between Aß positive SCD and control cases from Aß negative controls. These findings suggest that in prodromal stages of AD, such as in Aß positive MCI, multicenter DTI with prospectively harmonized acquisition parameters yields diagnostic accuracy meeting the criteria for a useful biomarker. In contrast, automated tract-based analysis of DTI parameters is not useful for the identification of preclinical AD, including Aß positive SCD and control cases.

2.
Br J Gen Pract ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31594770

RESUMO

BACKGROUND: Clinical judgement is intrinsic to diagnostic strategies in general practice; however, empirical evidence for its validity is sparse. AIM: To ascertain whether a GP's global clinical judgement of future cognitive status has an added value for predicting a patient's likelihood of experiencing dementia. DESIGN AND SETTING: Multicentre prospective cohort study among patients in German general practice that took place from January 2003 to October 2016. METHOD: Patients without baseline dementia were assessed with neuropsychological interviews over 12 years; 138 GPs rated the future cognitive decline of their participating patients. Associations of baseline predictors with follow-up incident dementia were analysed with mixed-effects logistic and Cox regression. RESULTS: A total of 3201 patients were analysed over the study period (mean age = 79.6 years, 65.3% females, 6.7% incident dementia in 3 years, 22.1% incident dementia in 12 years). Descriptive analyses and comparison with other cohorts identified the participants as having frequent and long-lasting doctor-patient relationships and being well known to their GPs. The GP baseline rating of future cognitive decline had significant value for 3-year dementia prediction, independent of cognitive test scores and patient's memory complaints (GP ratings of very mild (odds ratio [OR] 1.97, 95% confidence intervals [95% CI] = 1.28 to 3.04); mild (OR 3.00, 95% CI = 1.90 to 4.76); and moderate/severe decline (OR 5.66, 95% CI = 3.29 to 9.73)). GPs' baseline judgements were significantly associated with patients' 12-year dementia-free survival rates (Mantel-Cox log rank test P<0.001). CONCLUSION: In this sample of patients in familiar doctor-patient relationships, the GP's clinical judgement holds additional value for predicting dementia, complementing test performance and patients' self-reports. Existing and emerging primary care-based dementia risk models should consider the GP's judgement as one predictor. Results underline the importance of the GP-patient relationship.

3.
J Neurosci ; 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31541019

RESUMO

Mnemonic discrimination, the ability to distinguish similar events in memory, relies on subregions in the human medial temporal lobes (MTL). Tau pathology is frequently found within the MTL of older adults and therefore likely to affect mnemonic discrimination even in healthy older individuals. The MTL subregions that are known to be affected early by tau pathology, the perirhinal-transentorhinal region (area 35) and the anterior-lateral entorhinal cortex (alEC) have recently been implicated in the mnemonic discrimination of objects rather than scenes. Here we used an object-scene mnemonic discrimination task in combination with fMRI recordings and analyzed the relationship between subregional MTL activity, memory performance and levels of total and phosphorylated tau as well as Aß42/40 ratio in cerebrospinal fluid (CSF). We show that activity in alEC was associated with mnemonic discrimination of similar objects but not scenes in male and female cognitively unimpaired older adults. Importantly, CSF tau levels were associated with increased fMRI activity in the hippocampus and both, increased hippocampal activity as well as tau levels were associated with mnemonic discrimination of objects but again not scenes. This suggests that dysfunction of the alEC-hippocampus object mnemonic discrimination network might be a marker for tau-related cognitive decline.SIGNIFICANCE STATEMENTSubregions in the human medial temporal lobe (MTL) are critically involved in episodic memory and at the same time affected by tau pathology. Impaired object mnemonic discrimination performance as well as aberrant activity within the entorhinal-hippocampal circuitry have been reported in earlier studies involving older individuals but it has thus far remained elusive whether and how tau pathology is implicated in this specific impairment. Using task-related functional magnetic resonance imaging in combination with measures of tau pathology in cerebrospinal fluid, we show that measures of tau pathology are associated with increased hippocampal activity and reduced mnemonic discrimination of similar objects but not scenes. This suggests that object mnemonic discrimination tasks could be promising markers for tau-related cognitive decline.

4.
Nutrients ; 11(10)2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31561490

RESUMO

Research suggests that attention, mood, and satiety can be influenced by meal composition and postprandial activity. The present study examined whether this hypothesis applies to persons with a risk phenotype for the development of cardiovascular/neurodegenerative diseases. A randomized crossover trial was conducted in subjects with metabolic syndrome traits (n = 26, 8 female, age 70 ± 5, BMI 30.3 ± 2.3 kg/m2). Each subject participated in four interventions: iso-energetic (4300 kJ) meals (Western diet high-fat, WD, and Mediterranean-type diet, MD) followed by either 30 min of moderate walking (4.6 ± 0.1 km/h) or rest. Attention, mood, satiety and plasma cortisol concentrations were measured at fasting and 1.5, 3.0, 4.5 h postprandially. Data were analyzed by linear mixed models. In all interventions, attention increased continuously in the postprandial period (time effect, P < 0.001). After WD, attention was lower after walking compared to resting (meal × activity effect, P < 0.05). Postprandial mood was generally "good" with no intervention effects. Postprandial satiety increased reaching maximum at 1.5 h after meal (time effect, P < 0.001) and was higher after MD compared to WD (meal effect, P < 0.001). In all interventions, plasma cortisol decreased similar to its diurnal variation (time effect, P < 0.001). In our subjects, meal composition had no relevant impact on attention and mood. After typical WD, resting instead of walking seems to have a more beneficial effect on postprandial attention. MD leads to a strong and long-lasting feeling of satiety, possibly resulting in reduced energy intake in the further course of the day and, thus, long-term effect on weight control.

5.
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 certain areas of interest), and usability of eye-tracking glasses. RESULTS: Data from 13 participants were included. There were significant differences in dwell time 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.

6.
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.

7.
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.

8.
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.

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.
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.

11.
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.

12.
Aggress Behav ; 45(6): 610-621, 2019 Nov.
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.

13.
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
14.
Appl Environ Microbiol ; 85(20)2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31420340

RESUMO

"Candidatus 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°C, 46°C, 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 to 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 temperatures, the relative contributions of cren and cren' increased, while those of 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 the 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 thaumarchaeotal core lipid compositions revealed that the "Ca Nitrosotenuis 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 Nitrosotenuis uzonensis" cultures was distinct from those of other members of its order and was more similar to those of 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.

15.
Proc Natl Acad Sci U S A ; 116(38): 19116-19125, 2019 Sep 17.
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.

16.
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.

17.
Environ Microbiol ; 21(10): 3831-3854, 2019 Oct.
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.

18.
J Affect Disord ; 256: 650-657, 2019 Sep 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.

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.
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.

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