·POE is characterised by cortical thickening relative to EC.·Thickening occurs primarily in nodes of the CCN and DMN.·Interictal psychosis is characterised by cortical thickening in left occipital ...and temporal regions relative to EC.·This was also evident to a lesser extent in postictal psychosis.·A novel mechanism for cortical thickening in POE is proposed whereby normal synaptic pruning processes are interrupted by seizure onset.
To explore the cortical morphological associations of the psychoses of epilepsy.
Psychosis of epilepsy (POE) has two main subtypes - postictal psychosis and interictal psychosis. We used automated surface-based analysis of magnetic resonance images to compare cortical thickness, area, and volume across the whole brain between: (i) all patients with POE (n = 23) relative to epilepsy-without psychosis controls (EC; n = 23), (ii) patients with interictal psychosis (n = 10) or postictal psychosis (n = 13) relative to EC, and (iii) patients with postictal psychosis (n = 13) relative to patients with interictal psychosis (n = 10).
POE is characterised by cortical thickening relative to EC, occurring primarily in nodes of the cognitive control network; (rostral anterior cingulate, caudal anterior cingulate, middle frontal gyrus), and the default mode network (posterior cingulate, medial paracentral gyrus, and precuneus). Patients with interictal psychosis displayed cortical thickening in the left hemisphere in occipital and temporal regions relative to EC (lateral occipital cortex, lingual, fusiform, and inferior temporal gyri), which was evident to a lesser extent in postictal psychosis patients. There were no significant differences in cortical thickness, area, or volume between the postictal psychosis and EC groups, or between the postictal psychosis and interictal psychosis groups. However, prior to correction for multiple comparisons, both the interictal psychosis and postictal psychosis groups displayed cortical thickening relative to EC in highly similar regions to those identified in the POE group overall.
The results show cortical thickening in POE overall, primarily in nodes of the cognitive control and default mode networks, compared to patients with epilepsy without psychosis. Additional thickening in temporal and occipital neocortex implicated in the dorsal and ventral visual pathways may differentiate interictal psychosis from postictal psychosis. A novel mechanism for cortical thickening in POE is proposed whereby normal synaptic pruning processes are interrupted by seizure onset.
Serious injuries have been stated as a public health priority in the UK. However, there appears to be a lack of information on population-based rates of serious injury (as defined by a recognised ...taxonomy of injury severity) at national level from either official statistics or research papers. We aim to address this through a search and review of literature primarily focused within the UK and Europe.
The review summarizes research papers on the subject of population based injury epidemiology published from 1970 to 2008. We examined critically methodological approaches in measuring injury incident rates including data sources, description of the injury pyramid, matching numerator and denominator populations as well as the relationship between injury and socioeconomic status.
National representative rates come from research papers using official statistics sources, often focusing on mortality data alone. Few studies present data from the perspective of an injury pyramid or using a standardized measure of injury severity, i.e. Injury Severity Score (ISS). The population movement that may result in a possible numerator - denominator mismatch has been acknowledged in five research studies and in official statistics. The epidemiological profile shows over the past decades in UK and Europe a decrease in injury death rates. No major trauma population based rates are available within well defined populations across UK over recent time periods. Both fatal and non-fatal injury rates occurred more frequently in males than females with higher rates in males up to 65 years, then in females over 65 years. Road traffic crashes and falls are predominant injury mechanisms. Whereas a straightforward inverse association between injury death rates and socio-economic status has been observed, the evidence of socioeconomic inequalities in non-fatal injuries rates has not been wholly consistent.
New methodological approaches should be developed to deal with the study design inconsistencies and the knowledge gaps identified across this review. Trauma registries contain injury data from hospitals within larger regions and code injury by Abbreviated Injury Scale enabling information on severity; these may be reliable data sources to improve understanding of injury epidemiology.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Reports that globular proteins could enhance the interference blocking ability ofthe PPD (poly(o-phenylenediamine) layer used as a permselective barrier in biosensordesign, prompted this study where ...a variety of modifying agents were incorporated into PPDduring its electrosynthesis on Pt-Ir electrodes. Trapped molecules, including fibrous proteinsand β-cyclodextrin, altered the polymer/modifier composite selectivity by affecting thesensitivity to both H2O2 (signal molecule in many enzyme-based biosensors) and thearchetypal interference species, ascorbic acid. A comparison of electrochemical properties ofPt and a Pt-Ir alloy suggests that the benefits of the latter, more rigid, metal can be exploitedin PPD-based biosensor design without significant loss of backward compatibility withstudies involving pure Pt.
Clearance of acute infection with hepatitis C virus (HCV) is associated with the chr19q13.13 region containing the rs368234815 (TT/ΔG) polymorphism. We fine-mapped this region to detect possible ...causal variants that may contribute to HCV clearance. First, we performed sequencing of IFNL1-IFNL4 region in 64 individuals sampled according to rs368234815 genotype: TT/clearance (N = 16) and ΔG/persistent (N = 15) (genotype-outcome concordant) or TT/persistent (N = 19) and ΔG/clearance (N = 14) (discordant). 25 SNPs had a difference in counts of alternative allele >5 between clearance and persistence individuals. Then, we evaluated those markers in an association analysis of HCV clearance conditioning on rs368234815 in two groups of European (692 clearance/1 025 persistence) and African ancestry (320 clearance/1 515 persistence) individuals. 10/25 variants were associated (P < 0.05) in the conditioned analysis leaded by rs4803221 (P value = 4.9 × 10
) and rs8099917 (P value = 5.5 × 10
). In the European ancestry group, individuals with the haplotype rs368234815ΔG/rs4803221C were 1.7× more likely to clear than those with the rs368234815ΔG/rs4803221G haplotype (P value = 3.6 × 10
). For another nearby SNP, the haplotype of rs368234815ΔG/rs8099917T was associated with HCV clearance compared to rs368234815ΔG/rs8099917G (OR: 1.6, P value = 1.8 × 10
). We identified four possible causal variants: rs368234815, rs12982533, rs10612351 and rs4803221. Our results suggest a main signal of association represented by rs368234815, with contributions from rs4803221, and/or nearby SNPs including rs8099917.
The risk of transmission of HIV or hepatitis B from infectious health care workers to patients is low. However, inadvertent exposure causes great concern amongst patients of an infected health care ...worker. The patients of a Scottish dentist diagnosed hepatitis B e antigen positive were informed by letter of their exposure. A sample of patients was sent a postal questionnaire. Most (56%) respondents reported feeling anxious on receiving the letter but almost all (93%) thought patients should always be informed following treatment by an infectious health care worker, although the risk was very small. We discuss clinical and ethical factors relating to informing patients following exposure to an infectious health care worker. We suggest that a balance should be struck between patients' wishes to know of risks to which they have been exposed, however small, and the professional view that when risks are negligible, patients need not be informed.
Objective: Most trainees begin learning robotic minimally invasive surgery by performing inanimate practice tasks with clinical robots such as the Intuitive Surgical da Vinci. Expert surgeons are ...commonly asked to evaluate these performances using standardized five-point rating scales, but doing such ratings is time consuming, tedious, and somewhat subjective. This paper presents an automatic skill evaluation system that analyzes only the contact force with the task materials, the broad-bandwidth accelerations of the robotic instruments and camera, and the task completion time. Methods: We recruited N = 38 participants of varying skill in robotic surgery to perform three trials of peg transfer with a da Vinci Standard robot instrumented with our Smart Task Board. After calibration, three individuals rated these trials on five domains of the Global Evaluative Assessment of Robotic Skill (GEARS) structured assessment tool, providing ground-truth labels for regression and classification machine learning algorithms that predict GEARS scores based on the recorded force, acceleration, and time signals. Results: Both machine learning approaches produced scores on the reserved testing sets that were in good to excellent agreement with the human raters, even when the force information was not considered. Furthermore, regression predicted GEARS scores more accurately and efficiently than classification. Conclusion: A surgeon's skill at robotic peg transfer can be reliably rated via regression using features gathered from force, acceleration, and time sensors external to the robot. Significance: We expect improved trainee learning as a result of providing these automatic skill ratings during inanimate task practice on a surgical robot.
One gap in the medical community's understanding of the transmission of Legionnaire's disease is the size of the infective dose of the organism required to produce the disease in humans. Infective ...hazards are discussed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBJE, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
To provide insights into the biology of opioid dependence (OD) and opioid use (i.e., exposure, OE), we completed a genome-wide analysis comparing 4503 OD cases, 4173 opioid-exposed controls, and ...32,500 opioid-unexposed controls, including participants of European and African descent (EUR and AFR, respectively). Among the variants identified, rs9291211 was associated with OE (exposed vs. unexposed controls; EUR z = -5.39, p = 7.2 × 10
). This variant regulates the transcriptomic profiles of SLC30A9 and BEND4 in multiple brain tissues and was previously associated with depression, alcohol consumption, and neuroticism. A phenome-wide scan of rs9291211 in the UK Biobank (N > 360,000) found association of this variant with propensity to use dietary supplements (p = 1.68 × 10
). With respect to the same OE phenotype in the gene-based analysis, we identified SDCCAG8 (EUR + AFR z = 4.69, p = 10
), which was previously associated with educational attainment, risk-taking behaviors, and schizophrenia. In addition, rs201123820 showed a genome-wide significant difference between OD cases and unexposed controls (AFR z = 5.55, p = 2.9 × 10
) and a significant association with musculoskeletal disorders in the UK Biobank (p = 4.88 × 10
). A polygenic risk score (PRS) based on a GWAS of risk-tolerance (n = 466,571) was positively associated with OD (OD vs. unexposed controls, p = 8.1 × 10
; OD cases vs. exposed controls, p = 0.054) and OE (exposed vs. unexposed controls, p = 3.6 × 10
). A PRS based on a GWAS of neuroticism (n = 390,278) was positively associated with OD (OD vs. unexposed controls, p = 3.2 × 10
; OD vs. exposed controls, p = 0.002) but not with OE (p = 0.67). Our analyses highlight the difference between dependence and exposure and the importance of considering the definition of controls in studies of addiction.
Type I protein arginine methyltransferases (PRMTs) catalyze asymmetric dimethylation of arginines on proteins. Type I PRMTs and their substrates have been implicated in human cancers, suggesting ...inhibition of type I PRMTs may offer a therapeutic approach for oncology. The current report describes GSK3368715 (EPZ019997), a potent, reversible type I PRMT inhibitor with anti-tumor effects in human cancer models. Inhibition of PRMT5, the predominant type II PRMT, produces synergistic cancer cell growth inhibition when combined with GSK3368715. Interestingly, deletion of the methylthioadenosine phosphorylase gene (MTAP) results in accumulation of the metabolite 2-methylthioadenosine, an endogenous inhibitor of PRMT5, and correlates with sensitivity to GSK3368715 in cell lines. These data provide rationale to explore MTAP status as a biomarker strategy for patient selection.
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•GSK3368715 is a potent inhibitor of type I protein arginine methyltransferases•GSK3368715 alters exon usage and has activity against multiple cancer models•GSK3368715 synergizes with the PRMT5 inhibitor GSK3326595 to inhibit tumor growth•MTAP gene deficiency impairs PRMT5 activity, sensitizing cancer cells to GSK3368715
Fedoriw et al. show that the type I protein arginine methyltransferases (PRMT) inhibitor GSK3368715 has strong anti-cancer activity and synergizes with PRMT5 inhibition. MTAP deficiency causes accumulation of an endogenous PRMT5 inhibitor, suggesting MTAP status as a predictive biomarker for GSK3368715.
Abstract
Microbial ecology provides insights into the ecological and evolutionary dynamics of microbial communities underpinning every ecosystem on Earth. Microbial communities can now be ...investigated in unprecedented detail, although there is still a wealth of open questions to be tackled. Here we identify 50 research questions of fundamental importance to the science or application of microbial ecology, with the intention of summarising the field and bringing focus to new research avenues. Questions are categorised into seven themes: host–microbiome interactions; health and infectious diseases; human health and food security; microbial ecology in a changing world; environmental processes; functional diversity; and evolutionary processes. Many questions recognise that microbes provide an extraordinary array of functional diversity that can be harnessed to solve real-world problems. Our limited knowledge of spatial and temporal variation in microbial diversity and function is also reflected, as is the need to integrate micro- and macro-ecological concepts, and knowledge derived from studies with humans and other diverse organisms. Although not exhaustive, the questions presented are intended to stimulate discussion and provide focus for researchers, funders and policy makers, informing the future research agenda in microbial ecology.
We identify research questions in the field of microbial ecology, with emerging themes that recognise vast microbial functions that could benefit humanity, and the need to integrate knowledge across organisms.
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