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Facial expression and body posture recognition have protracted developmental trajectories. Interactions between face and body perception, such as the influence of body posture on facial expression perception, also change with development. While the brain regions underpinning face and body processing are well-defined, little is known about how white-matter tracts linking these regions relate to perceptual development. Here, we obtained complementary diffusion magnetic resonance imaging (MRI) measures (fractional anisotropy FA, spherical mean ), and a quantitative MRI myelin-proxy measure (R1), within white-matter tracts of face- and body-selective networks in children and adolescents and related these to perceptual development. In tracts linking occipital and fusiform face areas, facial expression perception was predicted by age-related microstructural development, as measured by and R1, as well as age-independent individual differences in microstructure, as measured by FA. Tract microstructure linking the body region in posterior superior temporal sulcus with anterior temporal lobe (ATL) was related to the influence of body on facial expression perception, supporting ATL as a site of face and body network convergence. Overall, our results highlight age-dependent and age-independent constraints that white-matter microstructure poses on perceptual abilities during development and the importance of complementary microstructural measures in linking brain structure and behaviour.

Objective Aim of the study was to compare working and non-working patients over a period of 12 months regarding socio-demographic, cancer-specific and mental health parameters. Methods This study was conducted as part of a Germany-wide longitudinal survey among 1398 patients in 13 national Comprehensive Cancer Centers. The sample used for analysis consisted of n = 430 cancer patients younger than 65 years (age M = 52.4 years, SD = 8.1; 67.0% females). Socio-demographic, cancer-specific and mental health parameters (Depression: Patient Health Questionnaire, Anxiety: Generalized Anxiety Disorder Scale, Distress: Distress Thermometer) were assessed at baseline during hospitalization and at 12 months follow-up. Results 73.7% of all patients (n = 317) have returned to work after one year. While working and non-working patients did not differ in socio-demographic parameters, there were significant differences in the presence of metastases, tumor and treatment status. Mixed analysis of variances revealed significant interactions between working status and time for depression (p = 0.009), anxiety (p = 0.003) and distress (p = 0.007). Non-working patients reported higher levels of depression, anxiety and distress than working patients over time. A logistic regression showed significant associations between lower depression (p = 0.019), lower distress (p = 0.033) and the absence of a tumor (p = 0.015) with working status. Conclusions The majority of cancer survivors returned to work. Non-working patients had higher levels of depression, anxiety and distress than working patients. After controlling for cancer-specific factors, mental health parameters were still independently associated with working status. Return to work can thus be associated with an improved mental health in cancer survivors. In order to establish causality, further research is necessary.

Colorectal cancer (CRC) is a high‐incidence malignancy worldwide which still needs better therapy options. Therefore, the aim of the present study was to investigate the responses of normal or malignant human intestinal epithelium to bone morphogenetic protein (BMP)‐9 and to find out whether the application of BMP‐9 to patients with CRC or the enhancement of its synthesis in the liver could be useful strategies for new therapy approaches. In silico analyses of CRC patient cohorts (TCGA database) revealed that high expression of the BMP‐target gene ID1, especially in combination with low expression of the BMP‐inhibitor noggin, is significantly associated with better patient survival. Organoid lines were generated from human biopsies of colon cancer (T‐Orgs) and corresponding non‐malignant areas (N‐Orgs) of three patients. The N‐Orgs represented tumours belonging to three different consensus molecular subtypes (CMS) of CRC. Overall, BMP‐9 stimulation of organoids promoted an enrichment of tumour‐suppressive gene expression signatures, whereas the stimulation with noggin had the opposite effects. Furthermore, treatment of organoids with BMP‐9 induced ID1 expression (independently of high noggin levels), while treatment with noggin reduced ID1. In summary, our data identify the ratio between ID1 and noggin as a new prognostic value for CRC patient outcome. We further show that by inducing ID1, BMP‐9 enhances this ratio, even in the presence of noggin. Thus, BMP‐9 is identified as a novel target for the development of improved anti‐cancer therapies of patients with CRC.

The medically important bacterial aromatic polyketide natural products typically feature a planar, polycyclic core structure. An exception is found for the rubromycins, whose backbones are disrupted by a bisbenzannulated [5,6]-spiroketal pharmacophore that was recently shown to be assembled by flavin-dependent enzymes. In particular, a flavoprotein monooxygenase proved critical for the drastic oxidative rearrangement of a pentangular precursor and the installment of an intermediate [6,6]-spiroketal moiety. Here we provide structural and mechanistic insights into the control of catalysis by this spiroketal synthase, which fulfills several important functions as reductase, monooxygenase, and presumably oxidase. The enzyme hereby tightly controls the redox state of the substrate to counteract shunt product formation, while also steering the cleavage of three carbon-carbon bonds. Our work illustrates an exceptional strategy for the biosynthesis of stable chroman spiroketals., Angewandte Chemie. International Edition, 60 (52), ISSN:1433-7851, ISSN:1521-3773, ISSN:0570-0833

A major contributor to coronavirus disease 2019 (COVID-19) progression and severity is a dysregulated innate and adaptive immune response. Interleukin-38 (IL-38) is an IL-1 family member with broad anti-inflammatory properties, but thus far little is known about its role in viral infections. Recent studies have shown inconsistent results, as one study finding an increase in circulating IL-38 in COVID-19 patients in comparison to healthy controls, whereas two other studies report no differences in IL-38 concentrations.Here, we present an exploratory, retrospective cohort study of circulating IL-38 concentrations in hospitalized COVID-19 patients admitted to two Dutch hospitals (discovery n = 148 and validation n = 184) and age- and sex-matched healthy subjects. Plasma IL-38 concentrations were measured by enzyme-linked immunosorbent assay, disease-related proteins by proximity extension assay, and clinical data were retrieved from hospital records.IL-38 concentrations were stable during hospitalization and similar to those of healthy control subjects. IL-38 was not associated with rates of intensive care unit admission or mortality. Only in men in the discovery cohort, IL-38 concentrations were positively correlated with hospitalization duration. A positive correlation between IL-38 and the inflammatory biomarker d-dimer was observed in men of the validation cohort. In women of the validation cohort, IL-38 concentrations correlated negatively with thrombocyte numbers. Furthermore, plasma IL-38 concentrations in the validation cohort correlated positively with TNF, TNFRSF9, IL-10Ra, neurotrophil 3, polymeric immunoglobulin receptor, CHL1, CD244, superoxide dismutase 2, and fatty acid binding protein 2, and negatively with SERPINA12 and cartilage oligomeric matrix protein.These data indicate that IL-38 is not associated with disease outcomes in hospitalized COVID-19 patients. However, moderate correlations between IL-38 concentrations and biomarkers of disease were identified in one of two cohorts. While we demonstrate that IL-38 concentrations are not indicative of COVID-19 severity, its anti-inflammatory effects may reduce COVID-19 severity and should be experimentally investigated.

Continuous glucose monitoring (CGM) systems are of great value for patients with disorders of impaired glucose homeostasis, including glycogen storage diseases. We report on an 8-year-old girl with glycogen storage disease type 9b who developed severe allergic contact dermatitis to two different continuous glucose monitoring systems, FreeStyle® Libre and Dexcom® G6. Our case highlights the impact of sensitization for pediatric patients, the urgent need for open labeling of components by pharmaceutical and device manufacturers, and the need for avoidance of skin sensitizers in medical devices.

BACKGROUND & AIMS Although transient elastography (TE) is used to determine liver stiffness as a surrogate to hepatic fibrosis, the normal range in children is not well defined. We performed a systematic review and individual participant data (IPD) meta-analysis to determine the range of liver stiffness in healthy children and evaluate the influence of important biological parameters. METHODS We pooled data from 10 studies that examined healthy children using TE. We divided 1702 children into two groups: ≥3 years (older group) and

Intravenous (IV) magnesium is used as an adjunct therapy in management of status asthmaticus with a goal of reducing intubation rate. A recent review suggests that IV magnesium use in status asthmaticus reduces admission rates. This is contrary to the observation of practicing emergency room physicians. The goal of this study was to assess trends in IV magnesium use for status asthmaticus in US children’s hospitals over 8 years through a retrospective analysis of children younger than 18 years using the Pediatric Health Information System database. Outcomes were IV magnesium use, inpatient and intensive care unit admission rate, geometric mean length of stay, and 7-day all-cause readmission rate. IV magnesium use for asthma hospitalization more than doubled over 8 years (17% vs. 36%; P < .001). Yearly trends were not significantly associated with hospital or intensive care unit admission rate or 7-day all-cause readmissions, although length of stay was reduced (P < .001).

Antimicrobial resistance represents a major threat to human health and knowledge of the underlying mechanisms is therefore vital. Here, we report the discovery and characterization of oxidoreductases that inactivate the broad-spectrum antibiotic chloramphenicol via dual oxidation of the C3-hydroxyl group. Accordingly, chloramphenicol oxidation either depends on standalone glucose-methanol-choline (GMC)-type flavoenzymes, or on additional aldehyde dehydrogenases that boost overall turnover. These enzymes also enable the inactivation of the chloramphenicol analogues thiamphenicol and azidamfenicol, but not of the C3-fluorinated florfenicol. Notably, distinct isofunctional enzymes can be found in Gram-positive (e. g., Streptomyces sp.) and Gram-negative (e. g., Sphingobium sp.) bacteria, which presumably evolved their selectivity for chloramphenicol independently based on phylogenetic analyses. Mechanistic and structural studies provide further insights into the catalytic mechanisms of these biotechnologically interesting enzymes, which, in sum, are both a curse and a blessing by contributing to the spread of antibiotic resistance as well as to the bioremediation of chloramphenicol.

Background Most inpatient care for children occurs outside tertiary children's hospitals, yet these facilities often dictate quality metrics. Our objective was to calculate the mean readmission rates and the Achievable Benchmarks of Care (ABCs) for pediatric diagnoses by different hospital types: metropolitan teaching, metropolitan nonteaching, and nonmetropolitan hospitals. Methods We used a cross-sectional retrospective study of 30-day, all-cause, same-hospital readmission of patients less than 18 years old using the 2014 Healthcare Utilization Project National Readmission Database. For each hospital type, we calculated the mean readmission rates and corresponding ABCs for the 17 most common readmission diagnoses. We define outlier as any hospital whose readmission rate fell outside the 95% CI for an ABC within their hospital type. Results We analyzed 690,949 discharges at 525 metropolitan teaching hospitals (550,039 discharges), 552 metropolitan nonteaching hospitals (97,207 discharges), and 587 nonmetropolitan hospitals (43,703 discharges). Variation in readmission rates existed among hospital types; however, sickle cell disease (SCD) had the highest readmission rate and ABC across all hospital types: metropolitan teaching hospitals 15.7% (ABC 7.0%), metropolitan nonteaching 14.7% (ABC 2.6%), and nonmetropolitan 12.8% (ABC not calculated). For diagnoses in which ABCs were available, outliers were prominent in bipolar disorders, major depressive disorders, and SCD. Conclusions ABCs based on hospital type may serve as a better metric to explain case-mix variation among different hospital types in pediatric inpatient care. The mean rates and ABCs for SCD and mental health disorders were much higher and with more outlier hospitals, which indicate high-value targets for quality improvement.

Objective This study aimed to test the hypothesis that attained adult height, as an indicator of childhood nutrition, is associated with diabetes in adulthood in Namibia, a country where stunting is highly prevalent. Methods Data from 1,898 women and 1,343 men aged 35 to 64 years included in the Namibia Demographic and Health Survey in 2013 were analyzed. Multiple logistic regression models were used to calculate odds ratios (ORs) and 95% CIs of having diabetes in relation to height. The following three models were considered: Model 1 included only height, Model 2 included height as well as demographic and socioeconomic variables, and Model 3 included body mass index in addition to the covariates from Model 2. Results Overall crude diabetes prevalence was 6.1% (95% CI: 5.0-7.2). Being taller was inversely related with diabetes in women but not in men. In Model 3, a 1-cm increase in women's height was associated with 4% lower odds of having diabetes (OR, 0.96; 95% CI: 0.94-0.99; P = 0.023). Conclusions Height is associated with a large reduction in diabetes in women but not in men in Namibia. Interventions that allow women to reach their full growth potential may help prevent the growing diabetes burden in the region.

The impact of COVID-19 public health interventions on pediatric illnesses nationwide is unknown. We performed a multicenter, cross-sectional study of encounters at 44 children’s hospitals in the United States to assess changes in healthcare utilization during the pandemic. The COVID-19 pandemic was associated with substantial reductions in encounters for respiratory diseases; these large reductions were consistent across illness subgroups. Although encounters for nonrespiratory diseases decreased as well, reductions were more modest and varied by age. Encounters for respiratory diseases among adolescents declined to a lesser degree and returned to previous levels faster compared with those of younger children. Further study is needed to determine the contributions of decreased illness and changes in care-seeking behavior to this observed reduction.

OBJECTIVE The study aimed to assess cancer patients' use of psychological care and its correlates in a large sample of cancer patients in Comprehensive Cancer Centers (CCCs) in Germany. METHODS In a multicenter study in Germany, cancer patients with various diagnoses were evaluated for self-reported use of psychological support. We measured psychological distress, depression and anxiety, quality of life, and social support with standardized questionnaires and analyzed its association with the utilization of psychological care using multivariable logistic regression. This paper focuses on a cross-sectional analysis of the data assessed during inpatient care. RESULTS Three thousand fifty-four (50%) of hospitalized patients were asked for participation, and n = 1632 (53.6%) participated. We were able to analyze n = 1,398 (45.9%) patients. Three hundred ninety-seven (28.4%) of the sample utilized psychological support. Users of psychological care were significantly younger than nonusers (odds ratio [OR]: 0.967, P

This study investigates the role of body image self-appraisal in predicting the outcomes of outpatient psychotherapy in patients with anorexia nervosa (AN). Multiple linear regression analyses and a path-analysis model were applied to test the study hypotheses that body image at baseline predicts treatment outcomes of outpatient psychotherapy in patients with AN at follow-up measurement. The analyses were conducted as secondary analyses in a subgroup (n = 148) of the anorexia nervosa treatment of outpatient-cohort (ANTOP-study) (N = 242) of patients with AN. The results show that Negative Evaluation of the Body at baseline predicts perceived stress during psychotherapy, which in turn predicts depressive symptoms at the end of therapy which in turn predicts the outcomes body mass index and EDI-2 sum score at 12 months follow-up. The results underline the importance of body image disturbance in the course of AN and call for body image as a central target of psychotherapeutic interventions in patients with AN.