The brain's supply and demand in obesity

During psychosocial stress, the brain demands extra energy from the body to satisfy its increased needs. For that purpose it uses a mechanism referred to as “cerebral insulin suppression” (CIS). Specifically, activation of the stress system suppresses insulin secretion from pancreatic beta-cells, and in this way energy—particularly glucose—is allocated to the brain rather than the periphery. It is unknown, however, how the brain of obese humans organizes its supply and demand during psychosocial stress. To answer this question, we examined 20 obese and 20 normal weight men in two sessions (Trier Social Stress Test and non-stress control condition followed by either a rich buffet or a meager salad). Blood samples were continuously taken and subjects rated their vigilance and mood by standard questionnaires. First, we found a low reactive stress system in obesity. While obese subjects showed a marked hormonal response to the psychosocial challenge, the cortisol response to the subsequent meal was absent. Whereas the brains of normal weight subjects demanded for extra energy from the body by using CIS, CIS was not detectable in obese subjects. Our findings suggest that the absence of CIS in obese subjects is due to the absence of their meal-related cortisol peak. Second, normal weight men were high reactive during psychosocial stress in changing their vigilance, thereby increasing their cerebral energy need, whereas obese men were low reactive in this respect. Third, normal weight subjects preferred carbohydrates after stress to supply their brain, while obese men preferred fat and protein instead. We conclude that the brain of obese people organizes its need, supply, and demand in a low reactive manner

Impulse dispersion of aerosols during playing the recorder and evaluation of safety measures

Introduction Group musical activities using wind instruments have been restricted during the CoVID19 pandemic due to suspected higher risk of virus transmission. It was presumed that the aerosols exhaled through the tubes while playing would be ejected over larger distances and spread into the room due to jet stream effects. In particular, the soprano recorder is widely used as an instrument in school classes, for beginners of all age groups in their musical education, in the context of leisure activities and in professional concert performances. Understanding the aerosol impulse dispersion characteristics of playing the soprano recorder could assist with the establishment of concepts for safe music-making. Methods Five adult professionally trained soprano recorder players (4 female, 1 male) played four bars of the main theme of L. van Beethoven’s “Ode to Joy” in low and in high octaves, as well as with 3 different potential protection devices in the high octave. For comparison they spoke the corresponding text by F. Schiller. Before each task, they inhaled .5 L of vapor from an e-cigarette filled with base liquid. The vapor cloud escaping during speaking or playing was recorded by cameras and its spread was measured as a function of time in the three spatial dimensions. The potential safety devices were rated for practicability with a questionnaire, and their influence on the sound was compared, generating a long-term average spectrum from the audio data. Results When playing in the high octave, at the end of the task the clouds showed a median distance of 1.06 m to the front and .57 m diameter laterally (maxima: x: 1.35 m and y: .97 m). It was found that the clouds’ expansion values in playing the recorder with and without safety measures are mostly lower when compared to the ordinary, raised speaking voice of the same subjects. The safety devices which covered the instrument did not show clear advantages and were rated as unpractical by the subjects. The most effective reduction of the cloud was reached when playing into a suction funnel. Conclusion The aerosol dispersion characteristics of soprano recorders seem comparable to clarinets. The tested safety devices which covered holes of the instrument did not show clear benefits

Towards a practical theory for commercializing novel continuous living cover crops: a conceptual review through the lens of Kernza perennial grain, 2019–2022

As agricultural scientists rapidly develop and deploy novel continuous living cover (CLC) crops and cropping systems such as perennial grains, a growing number of intermediaries are engaged in advancing the commercialization, adoption, and scaling of these novel CLC crops. However, these commercialization practitioners lack a conceptual and practical roadmap to help them achieve success. Through key concept review and practice narratives, this article presents the firsthand experience of primarily non-academic staff at several key public and nonprofit agricultural innovation platforms between 2019 and 2022 that have held core institutional responsibilities for facilitating the commercialization, adoption, and scaling of Kernza® perennial grain, North America’s first commercially-viable perennial grain crop. Reviews of key concepts identified as relevant to the practice of commercializing novel continuous living cover crops are interwoven with practice narratives of the Kernza commercialization process through the lens of each concept, demonstrating the ways in which these concepts translate to specific activities, methods, and strategies, also noting remaining gaps, limitations, and areas for growth and learning. This narrative can move the growing community of CLC intermediaries and innovation brokers toward a ‘practical theory’ of CLC commercialization that lies at the intersection of technology transfer and adoption, innovation, and agri-food systems change processes. Such conceptual orientation and practical guidance stands to improve the efficacy of novel CLC crop commercialization intermediaries, accelerate wider efforts of agricultural innovation platforms to rapidly advance CLC agriculture, and provide fertile ground for further applied research

Machine-learning based exploration of determinants of gray matter volume in the KORA-MRI study

To identify the most important factors that impact brain volume, while accounting for potential collinearity, we used a data-driven machine-learning approach. Gray Matter Volume (GMV) was derived from magnetic resonance imaging (3T, FLAIR) and adjusted for intracranial volume (ICV). 93 potential determinants of GMV from the categories sociodemographics, anthropometric measurements, cardio-metabolic variables, lifestyle factors, medication, sleep, and nutrition were obtained from 293 participants from a population-based cohort from Southern Germany. Elastic net regression was used to identify the most important determinants of ICV-adjusted GMV. The four variables age (selected in each of the 1000 splits), glomerular filtration rate (794 splits), diabetes (323 splits) and diabetes duration (122 splits) were identified to be most relevant predictors of GMV adjusted for intracranial volume. The elastic net model showed better performance compared to a constant linear regression (mean squared error = 1.10 vs. 1.59, p<0.001). These findings are relevant for preventive and therapeutic considerations and for neuroimaging studies, as they suggest to take information on metabolic status and renal function into account as potential confounders

Low-level APC mutational mosaicism is the underlying cause in a substantial fraction of unexplained colorectal adenomatous polyposis cases

Background In 30-50% of patients with colorectal adenomatous polyposis, no germline mutation in the known genes APC, causing familial adenomatous polyposis, MUTYH, causing MUTYH-associated polyposis, or POLE or POLD1, causing polymerase-proofreading-associated polyposis can be identified, although a hereditary aetiology is likely. This study aimed to explore the impact of APC mutational mosaicism in unexplained polyposis. Methods To comprehensively screen for somatic low-level APC mosaicism, high-coverage next-generation sequencing of the APC gene was performed using DNA from leucocytes and a total of 53 colorectal tumours from 20 unrelated patients with unexplained sporadic adenomatous polyposis. APC mosaicism was assumed if the same loss-of-function APC mutation was present in 2 anatomically separated colorectal adenomas/carcinomas per patient. All mutations were validated using diverse methods. Results In 25% (5/20) of patients, somatic mosaicism of a pathogenic APC mutation was identified as underlying cause of the disease. In 2/5 cases, the mosaic level in leucocyte DNA was slightly below the sensitivity threshold of Sanger sequencing;while in 3/5 cases, the allelic fraction was either very low (0.1-1%) or no mutations were detectable. The majority of mosaic mutations were located outside the somatic mutation cluster region of the gene. Conclusions The present data indicate a high prevalence of pathogenic mosaic APC mutations below the detection thresholds of routine diagnostics in adenomatous polyposis, even if high-coverage sequencing of leucocyte DNA alone is taken into account. This has important implications for both routine work-up and strategies to identify new causative genes in this patient group

Nine newly identified individuals refine the phenotype associated with MYT1L mutations

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Situation of child and adolescent health in Europe

To promote child health in Europe, the World Health Organization Regional Office for Europe developed the child and adolescent health strategy (2015–2020), which was adopted by all Member States of the WHO European Region. The strategy’s implementation was monitored through country profiles compiling existing health data and a survey sent to all 53 European ministries of health. Responses from 48 countries are described graphically, quantitatively and qualitatively. This report helps to review achievements and address gaps in realizing the full potential for the health and well-being of children and adolescents

Scaling carbon fluxes from eddy covariance sites to globe: Synthesis and evaluation of the FLUXCOM approach

FLUXNET assembles globally-distributed eddy covariance-based estimates of carbon fluxes between the biosphere and the atmosphere. Since eddy covariance flux towers have a relatively small footprint and are distributed unevenly across the world, upscaling the observations is necessary in order to obtain global-scale estimates of biosphere-atmosphere exchange from the flux tower network. Based on cross-consistency checks with atmospheric inversions, sun-induced fluorescence (SIF) and dynamic global vegetation models (DGVM), we provide here a systematic assessment of the latest upscaling efforts for gross primary production (GPP) and net ecosystem exchange (NEE) of the FLUXCOM initiative, where different machine learning methods, forcing datasets, and sets of predictor variables were employed. Spatial patterns of mean GPP are consistent among FLUXCOM and DGVM ensembles (R2 > 0.94 at 1° spatial resolution) while the majority of DGVMs are outside the FLUXCOM range for 70 % of the land surface. Global mean GPP magnitudes for 2008–2010 from FLUXCOM members vary within 106 and 130 PgC yr−1 with the largest uncertainty in the tropics. Seasonal variations of independent SIF estimates agree better with FLUXCOM GPP (mean global pixel-wise R2 ~ 0.75) than with GPP from DGVMs (mean global pixel wise R2 ~ 0.6). Seasonal variations of FLUXCOM NEE show good consistency with atmospheric inversion-based net land carbon fluxes, particularly for temperate and boreal regions (R2 > 0.92). Interannual variability of global NEE in FLUXCOM is underestimated compared to inversions and DGVMs. The FLUXCOM version which uses also meteorological inputs shows a strong co-variation of interannual patterns with inversions (R2 = 0.88 for 2001–2010). Mean regional NEE from FLUXCOM shows larger uptake than inversion and DGVM-based estimates, particularly in the tropics with discrepancies of up to several hundred gC m2 yr−1. These discrepancies can only partly be reconciled by carbon loss pathways that are implicit in inversions but not captured by the flux tower measurements such as carbon emissions from fires and water bodies. We hypothesize that a combination of systematic biases in the underlying eddy covariance data, in particular in tall tropical forests, and a lack of site-history effects on NEE in FLUXCOM are likely responsible for the too strong tropical carbon sink estimated by FLUXCOM. Furthermore, as FLUXCOM does not account for CO2 fertilization effects carbon flux trends are not realistic. Overall, current FLUXCOM estimates of mean annual and seasonal cycles of GPP as well as seasonal NEE variations provide useful constraints of global carbon cycling, while interannual variability patterns from FLUXCOM are valuable but require cautious interpretation. Exploring the diversity of Earth Observation data and of machine learning concepts along with improved quality and quantity of flux tower measurements will facilitate further improvements of the FLUXCOM approach overall

Mutations in <em>GRHL2</em> result in an autosomal-recessive ectodermal dysplasia syndrome

Grainyhead-like 2, encoded by GRHL2, is a member of a highly conserved family of transcription factors that play essential roles during epithelial development. Haploinsufficiency for GRHL2 has been implicated in autosomal-dominant deafness, but mutations have not yet been associated with any skin pathology. We investigated two unrelated Kuwaiti families in which a total of six individuals have had lifelong ectodermal defects. The clinical features comprised nail dystrophy or nail loss, marginal palmoplantar keratoderma, hypodontia, enamel hypoplasia, oral hyperpigmentation, and dysphagia. In addition, three individuals had sensorineural deafness, and three had bronchial asthma. Taken together, the features were consistent with an unusual autosomal-recessive ectodermal dysplasia syndrome. Because of consanguinity in both families, we used whole-exome sequencing to search for novel homozygous DNA variants and found GRHL2 mutations common to both families: affected subjects in one family were homozygous for c.1192T>C (p.Tyr398His) in exon 9, and subjects in the other family were homozygous for c.1445T>A (p.Ile482Lys) in exon 11. Immortalized keratinocytes (p.Ile482Lys) showed altered cell morphology, impaired tight junctions, adhesion defects, and cytoplasmic translocation of GRHL2. Whole-skin transcriptomic analysis (p.Ile482Lys) disclosed changes in genes implicated in networks of cell-cell and cell-matrix adhesion. Our clinical findings of an autosomal-recessive ectodermal dysplasia syndrome provide insight into the role of GRHL2 in skin development, homeostasis, and human disease

Pressurized intraperitoneal aerosol chemotherapy (PIPAC): updated systematic review using the IDEAL framework

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a surgical innovation deployed to treat peritoneal metastases. Traditionally, peritoneal metastases have been treated with systemic chemotherapy, but this approach is limited by poor peritoneal perfusion. Intra-abdominal chemotherapy in the form of heated lavage (hyperthermic intraperitoneal chemotherapy (HIPEC)) is currently used alongside cytoreductive surgery. The use of aerosolized agents in a laparoscopic setting was first described in 2000 in a swine model1; since then, a number of PIPAC studies have been reported. The IDEAL framework2 provides recommendations for the design, development, and reporting of studies for novel surgical interventions (Table 1). It recommends that innovations move through stages (idea, development, exploration, assessment, and long-term studies)