Trial-by-Trial Adjustments of Cognitive Control Following Errors and Response Conflict are Altered in Pediatric Obsessive Compulsive Disorder

Background: Impairments of cognitive control have been theorized to drive the repetitive thoughts and behaviors of obsessive compulsive disorder (OCD) from early in the course of illness. However, it remains unclear whether altered trial-by-trial adjustments of cognitive control characterize young patients. To test this hypothesis, we determined whether trial-by-trial adjustments of cognitive control are altered in children with OCD, relative to healthy controls. Methods: Forty-eight patients with pediatric OCD and 48 healthy youth performed the Multi-Source Interference Task. Two types of trial-by-trial adjustments of cognitive control were examined: post-error slowing (i.e., slower responses after errors than after correct trials) and post-conflict adaptation (i.e., faster responses in high-conflict incongruent trials that are preceded by other high-conflict incongruent trials, relative to low-conflict congruent trials). Results: While healthy youth exhibited both post-error slowing and post-conflict adaptation, patients with pediatric OCD failed to exhibit either of these effects. Further analyses revealed that patients with low symptom severity showed a reversal of the post-conflict adaptation effect, whereas patients with high symptom severity did not show any post-conflict adaptation. Conclusion: Two types of trial-by-trial adjustments of cognitive control are altered in pediatric OCD. These abnormalities may serve as early markers of the illness

Alteration of intracellular cysteine and glutathione levels in alveolar macrophages and lymphocytes by diesel exhaust particle exposure.

The purpose of this study was to characterize the effects of diesel exhaust particles (DEP) on thiol regulation in alveolar macrophages (AM) and lymphocytes. We obtained AM and lymph node (thymic and tracheal) cells (LNC) (at different time points) from rats exposed intratracheally to DEP (5 mg/kg) or saline, and measured inflammatory markers, thiol levels, and glutathione reductase (GSH-R) activity. DEP exposure produced significant increases in neutrophils, lactate dehydrogenase, total protein, and albumin content in the lavage fluid. AM from DEP-exposed rats showed a time-dependent increase in intracellular cysteine (CYSH) and GSH. In LNC the intracellular GSH reached peak level by 24 hr, declining toward control levels by 72 hr after exposure. LNC-CYSH and AM-CYSH and GSH were increased at both 24 and 72 hr. Both Sprague-Dawley and Brown Norway rats showed similar trends of responses to DEP exposure as per measurement of the inflammatory markers and thiol changes. AM and, to a lesser degree, LNC were both active in cystine uptake. The DEP exposure stimulated GSH-R activity and increased the conversion of cystine to CYSH in both cell types. The intracellular level of GSH in DEP-exposed AM was moderately increased compared with the saline control, and was further augmented when cells were incubated with cystine. In contrast, the intracellular level of GSH in DEP-exposed LNC was significantly reduced despite the increased CYSH level and GSH-R activity when these cells were cultured for 16 hr. DEP absorbed 23-31% of CYSH, cystine, and GSH, and only 8% of glutathione disulfide when incubated in cell free media. These results indicate that DEP exposure caused lung inflammation and affected thiol levels in both AM and LNC

Single-cell analysis of long non-coding RNAs in the developing human neocortex

Single cell transcriptomics of lncRNA expression in K562 cell cultures. A Distributions of median lncRNA expression to median mRNA expression ratios (lncRNA:mRNA) in populations, in silico merged single cells, and single cells from K562 cultures. B Proportion of K562 cells that expressed each lncRNA (blue) and mRNA (red), separated by maximum expression in single cells. C Same as in (B) but grouped by maximum expression quantile. D Distributions of non-zero lncRNA (blue) and mRNA (red) expression in 46 single K562 cells. Green squares, housekeeping genes; black triangles, ERCC Spike-In Controls. (PDF 454 kb

The Science of Sungrazers, Sunskirters, and Other Near-Sun Comets

This review addresses our current understanding of comets that venture close to the Sun, and are hence exposed to much more extreme conditions than comets that are typically studied from Earth. The extreme solar heating and plasma environments that these objects encounter change many aspects of their behaviour, thus yielding valuable information on both the comets themselves that complements other data we have on primitive solar system bodies, as well as on the near-solar environment which they traverse. We propose clear definitions for these comets: We use the term near-Sun comets to encompass all objects that pass sunward of the perihelion distance of planet Mercury (0.307 AU). Sunskirters are defined as objects that pass within 33 solar radii of the Sun’s centre, equal to half of Mercury’s perihelion distance, and the commonly-used phrase sungrazers to be objects that reach perihelion within 3.45 solar radii, i.e. the fluid Roche limit. Finally, comets with orbits that intersect the solar photosphere are termed sundivers. We summarize past studies of these objects, as well as the instruments and facilities used to study them, including space-based platforms that have led to a recent revolution in the quantity and quality of relevant observations. Relevant comet populations are described, including the Kreutz, Marsden, Kracht, and Meyer groups, near-Sun asteroids, and a brief discussion of their origins. The importance of light curves and the clues they provide on cometary composition are emphasized, together with what information has been gleaned about nucleus parameters, including the sizes and masses of objects and their families, and their tensile strengths. The physical processes occurring at these objects are considered in some detail, including the disruption of nuclei, sublimation, and ionisation, and we consider the mass, momentum, and energy loss of comets in the corona and those that venture to lower altitudes. The different components of comae and tails are described, including dust, neutral and ionised gases, their chemical reactions, and their contributions to the near-Sun environment. Comet-solar wind interactions are discussed, including the use of comets as probes of solar wind and coronal conditions in their vicinities. We address the relevance of work on comets near the Sun to similar objects orbiting other stars, and conclude with a discussion of future directions for the field and the planned ground- and space-based facilities that will allow us to address those science topics

Colorectal cancer among inflammatory bowel disease patients: risk factors and prevalence compared to the general population

BackgroundColorectal cancer (CRC) is a feared complication of inflammatory bowel disease (IBD). We aimed to investigate the prevalence and risk factors of CRC among a large cohort of IBD patients.MethodsData on IBD patients free of CRC at baseline was extracted using the MDClone platform of the Clalit health maintenance organization in Israel. We investigated the frequency rate of CRC among IBD patients compared to a control group without IBD. Possible risk factors, including comorbidities and IBD-related medications, were investigated in a multivariate analysis.ResultsDuring a follow-up of 139,448 years among Crohn’s disease (CD) patients and 139,533 years among ulcerative colitis (UC) patients, a frequency rate of CRC was 1.5% (191) among 12,888 CD patients and 2.1% (261) among 12,381 UC patients compared to 1.2% among 57,334 controls. In a multivariate analysis of UC patients, age at diagnosis (OR 1.030, p < 0.001), primary sclerosing cholangitis (OR 2.487, p = 0.005), diabetes mellitus (OR 2.01, p < 0.001), and glucocorticoids treatment (OR 1.465, p = 0.008) were found to be predictors of CRC. For CD patients, age at diagnosis (OR 1.035, p < 0.001), primary sclerosing cholangitis (OR 2.25, p = 0.029), and glucocorticoids treatment (OR 2.07, p < 0.001) were found to be predictors for CRC, but not diabetes mellitus.ConclusionDespite the continuously decreasing rates of CRC among IBD patients, these are still higher in IBD patients compared to the general population. IBD patients, particularly those with risk factors, require special consideration in follow-up for CRC

Microevolution of Helicobacter pylori during prolonged infection of single hosts and within families

Our understanding of basic evolutionary processes in bacteria is still very limited. For example, multiple recent dating estimates are based on a universal inter-species molecular clock rate, but that rate was calibrated using estimates of geological dates that are no longer accepted. We therefore estimated the short-term rates of mutation and recombination in Helicobacter pylori by sequencing an average of 39,300 bp in 78 gene fragments from 97 isolates. These isolates included 34 pairs of sequential samples, which were sampled at intervals of 0.25 to 10.2 years. They also included single isolates from 29 individuals (average age: 45 years) from 10 families. The accumulation of sequence diversity increased with time of separation in a clock-like manner in the sequential isolates. We used Approximate Bayesian Computation to estimate the rates of mutation, recombination, mean length of recombination tracts, and average diversity in those tracts. The estimates indicate that the short-term mutation rate is 1.4×10−6 (serial isolates) to 4.5×10−6 (family isolates) per nucleotide per year and that three times as many substitutions are introduced by recombination as by mutation. The long-term mutation rate over millennia is 5–17-fold lower, partly due to the removal of non-synonymous mutations due to purifying selection. Comparisons with the recent literature show that short-term mutation rates vary dramatically in different bacterial species and can span a range of several orders of magnitude

Impact of Rheumatic Musculoskeletal Disease on Psychological Development in Adolescents and Young Adults

Adolescents and young adults (AYAs) undergo significant physiological and psychological transformations. When developmental milestones are combined with additional challenges of growing up with a chronic rheumatic musculoskeletal disease (RMD), it can increase AYA's susceptibility to psychological problems. Emotional issues in adolescence can often persist into adulthood and negatively impact future health, social, and work outcomes. This chapter summarises psychological challenges for AYAs and recommends ways for healthcare professionals (HCPs) to promote mental wellbeing in AYAs with RMD

Impact of COVID-19 in patients on active melanoma therapy and with history of melanoma

INTRODUCTION: COVID-19 particularly impacted patients with co-morbid conditions, including cancer. Patients with melanoma have not been specifically studied in large numbers. Here, we sought to identify factors that associated with COVID-19 severity among patients with melanoma, particularly assessing outcomes of patients on active targeted or immune therapy. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, we identified 307 patients with melanoma diagnosed with COVID-19. We used multivariable models to assess demographic, cancer-related, and treatment-related factors associated with COVID-19 severity on a 6-level ordinal severity scale. We assessed whether treatment was associated with increased cardiac or pulmonary dysfunction among hospitalized patients and assessed mortality among patients with a history of melanoma compared with other cancer survivors. RESULTS: Of 307 patients, 52 received immunotherapy (17%), and 32 targeted therapy (10%) in the previous 3 months. Using multivariable analyses, these treatments were not associated with COVID-19 severity (immunotherapy OR 0.51, 95% CI 0.19 - 1.39; targeted therapy OR 1.89, 95% CI 0.64 - 5.55). Among hospitalized patients, no signals of increased cardiac or pulmonary organ dysfunction, as measured by troponin, brain natriuretic peptide, and oxygenation were noted. Patients with a history of melanoma had similar 90-day mortality compared with other cancer survivors (OR 1.21, 95% CI 0.62 - 2.35). CONCLUSIONS: Melanoma therapies did not appear to be associated with increased severity of COVID-19 or worsening organ dysfunction. Patients with history of melanoma had similar 90-day survival following COVID-19 compared with other cancer survivors

Michigan Neural Distinctiveness (MiND) study protocol: investigating the scope, causes, and consequences of age-related neural dedifferentiation

Abstract Background Aging is often associated with behavioral impairments, but some people age more gracefully than others. Why? One factor that may play a role is individual differences in the distinctiveness of neural representations. Previous research has found that neural activation patterns in visual cortex in response to different visual stimuli are often more similar (i.e., less distinctive) in older vs. young participants, a phenomenon referred to as age-related neural dedifferentiation. Furthermore, older people whose neural representations are less distinctive tend to perform worse on a wide range of behavioral tasks. The Michigan Neural Distinctiveness (MiND) project aims to investigate the scope of neural dedifferentiation (e.g., does it also occur in auditory, motor, and somatosensory cortex?), one potential cause (age-related reductions in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)), and the behavioral consequences of neural dedifferentiation. This protocol paper describes the study rationale and methods being used in complete detail, but not the results (data collection is currently underway). Methods The MiND project consists of two studies: the main study and a drug study. In the main study, we are recruiting 60 young and 100 older adults to perform behavioral tasks that measure sensory and cognitive function. They also participate in functional MRI (fMRI), MR spectroscopy, and diffusion weighted imaging sessions, providing data on neural distinctiveness and GABA concentrations. In the drug study, we are recruiting 25 young and 25 older adults to compare neural distinctiveness, measured with fMRI, after participants take a placebo or a benzodiazepine (lorazepam) that should increase GABA activity. Discussion By collecting multimodal imaging measures along with extensive behavioral measures from the same subjects, we are linking individual differences in neurochemistry, neural representation, and behavioral performance, rather than focusing solely on group differences between young and old participants. Our findings have the potential to inform new interventions for age-related declines. Trial registration This study was retrospectively registered with the ISRCTN registry on March 4, 2019. The registration number is ISRCTN17266136 .https://deepblue.lib.umich.edu/bitstream/2027.42/148569/1/12883_2019_Article_1294.pd

Remission Of Maternal Depression And Child Symptoms Among Single Mothers: A Star*d-child Report

Objective: Offspring of depressed parents are at increased risk for depressive and other disorders. We recently found that when depressed mothers reached full remission over 3 months of treatment, a significant improvement in the children’s disorders occurred. Since only a third of the mothers remitted, factors related to maternal remission rates, and thereby child outcomes, were important. This report examined the relationship of the presence of a father in the household to maternal depression remission and child outcomes. Method: Maternal depression was measured using the 17-item Hamilton Rating Scale for Depression (HRSD17); social functioning was assessed using the Social Adjustment Scale-Self Report (SAS-SR). Children (age 7–17) were assessed independently, blind to maternal outcome, using the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS-PL) and the Child Global Assessment Scale (C-GAS). Results: Single mothers (n = 50), as compared to those in two-parent households (n = 61), were more likely to discontinue treatment (31% vs. 16%, P = 0.04), and less likely to remit if they remained in treatment (20% vs. 43%, P = 0.013). These differences remained significant after adjusting for socioeconomic status and potential confounders, but were partially explained by the mother’s pre-treatment social functioning. The reduction in child diagnoses following maternal remission was greater in two-parent than in single-parent households, although a formal test of interaction between the odds ratios was not significant. Conclusion: Single depressed mothers are more likely to drop out of treatment, and less likely to reach remission if they stay in treatment. This high-risk group requires vigorous treatment approaches