The transcription factor RUNX1 is a critical regulator of developmental hematopoiesis and is frequently disrupted in leukemia. Runx1 is a large, complex gene that is expressed from two alternative ...promoters under the spatiotemporal control of multiple hematopoietic enhancers. To dissect the dynamic regulation of Runx1 in hematopoietic development, we analyzed its three-dimensional chromatin conformation in mouse embryonic stem cell (ESC) differentiation cultures. Runx1 resides in a 1.1 Mb topologically associating domain (TAD) demarcated by convergent CTCF motifs. As ESCs differentiate to mesoderm, chromatin accessibility, Runx1 enhancer-promoter (E-P) interactions, and CTCF-CTCF interactions increase in the TAD, along with initiation of Runx1 expression from the P2 promoter. Differentiation to hematopoietic progenitor cells is associated with the formation of tissue-specific sub-TADs over Runx1, a shift in E-P interactions, P1 promoter demethylation, and robust expression from both Runx1 promoters. Deletion of promoter-proximal CTCF sites at the sub-TAD boundaries has no obvious effects on E-P interactions but leads to partial loss of domain structure, mildly affects gene expression, and delays hematopoietic development. Together, our analysis of gene regulation at a large multi-promoter developmental gene reveals that dynamic sub-TAD chromatin boundaries play a role in establishing TAD structure and coordinated gene expression.
This article describes trends and stability over time in health complaints in adolescents from 2002 to 2010 and investigates associations between health complaints, behavioural and social contextual ...factors at individual level and economic factors at macro-level.
Comprising N = 510 876 11-, 13- and 15-year-old children and adolescents in Europe, North America and Israel, data came from three survey cycles of the international Health Behaviour in School-aged Children (HBSC) study. Age- and gender-adjusted trends in health complaints were examined in each country by means of linear regression. By using the country as the random effects variable, we tested to what extent individual and contextual variables were associated with health complaints.
Significant associations are stronger for individual level determinants (e.g. being bullied, smoking) than for determinants at macro-level (e.g. GDP, Gini), as can be seen by the small effect sizes (less than 5% for different trends). Health complaints are fairly stable over time in most countries, and no clear international trend in health complaints can be observed between 2002 and 2010. The most prominent stable determinants were being female, being bullied, school pressure and smoking.
Factors associated with health complaints are more related to the proximal environment than to distal macro-level factors. This points towards intensifying targeted interventions, (e.g. for bullying) and also targeting specific risk groups. The comparably small effect size at country-level indicates that country-level factors have an impact on health and should not be ignored.
Health complaints are a good indicator of an individual's psychosocial health and well-being. Studies have shown that children and adolescents report health complaints which can cause significant ...individual burden.
Using data from the international Health Behaviour in School-aged Children study, this article describes trends in multiple recurrent health complaints (MHC) in 35 countries among N = 237 136 fifteen-year-olds from 1994 to 2010. MHC was defined as the presence of two or more health complaints at least once a week. Logistic regression analysis was performed to evaluate trends across the five survey cycles for each country.
Lowest prevalence throughout the period 1994-2010 was 16.9% in 1998 in Austria and highest in 2006 in Israel (54.7%). Overall, six different trend patterns could be identified: No linear or quadratic trend (9 countries), linear decrease (7 countries), linear increase (5 countries), U-shape (4 countries), inverted U-shape (6 countries) and unstable (4 countries).
Trend analyses are valuable in providing hints about developments in populations as well as for benchmarking and evaluation purposes. The high variation in health complaints between the countries requires further investigation, but may also reflect the subjective nature of health complaints.
Chronic rhinosinusitis (CRS) presents a multifactorial etiology due to interactions between the immune host system and external agents. It can be classified into two phenotypes based on the presence ...or absence of polypoid neoformation (respectively CRSwNP and CRSsNP). According to EPOS2020, CRS is now classified into two endotypes, eosinophilic (ECRS) and non-eosinophilic (non-ECRS), based on eosinophil tissue count (more than 10 eosinophils per High Power Field, HPF).
We present the case of a 31-year-old man affected by recalcitrant ECRSwNP and asthma.
He was treated with a combination of omalizumab and endoscopic sinus surgery. This combination led to a reduction in blood eosinophils, modified Lund-Kennedy endoscopic score, Lund-Mackay score, and Sino-Nasal Outcome Test (SNOT-22), almost 6 months after surgery.
In this clinical case, omalizumab regulated nasal symptoms for more than a year and with good control of the recalcitrant pattern when combined with ESS.
The synthesis and structural characterization of a series of palladium complexes bearing N-heterocyclic carbenes (NHC) as supporting ligands are described. The reaction of commercially available ...Pd(allyl)Cl2 and isolated or in situ generated NHC leads to monomeric palladium complexes where one NHC is bound to the metal center, as indicated by spectroscopic and single-crystal X-ray diffraction studies. The relative reactivity trend for these complexes as catalysts in aryl amination is discussed in terms of ligand steric properties, which vary as a function of imidazole-nitrogen substituents and perturbation resulting in modulation of ring planarity. The concept of buried volume is used to quantify the steric demand of each NHC in the corresponding complexes.
Insulin resistance and hyperinsulinemia are often considered intrinsic features of the polycystic ovary syndrome (PCOS). Nevertheless, conflicting results of insulin sensitivity and secretion have ...been obtained in the subgroup of normal-weight women with PCOS. Differences in body composition, ethnicity, and diet composition and a family history of metabolic diseases may act as confounding variables in women with PCOS. In the present study, insulin sensitivity and secretion were estimated by an iv glucose tolerance test (IVGTT), analyzed by minimal models, in 20 normal-weight healthy women with PCOS and no family history of type 2 diabetes mellitus and in 20 normally ovulating women, matched for age and body mass index. Insulin sensitivity mean (95% confidence intervals); PCOS 4.0 (2.8–5.1) vs. controls 4.5 (3.5–5.4) 10−4 min−1/μU·ml, and insulin secretion, expressed as the acute insulin response to glucose PCOS 3.7 (3.3–4.2) vs. controls 3.7 (3.4–4.0) μU/ml were similar in the two groups. The women with PCOS showed an increased proportion of total body fat (PCOS 29% vs. controls 27.2%; P < 0.01). They also showed decreased glucose effectiveness, i.e. the proportion of glucose uptake independent from insulin activity PCOS 2.6 (2.1–3.0) vs. controls 3.8 (3.0–4.6) mg × 100 min−1; P = 0.01. The levels of insulin sensitivity and of glucose effectiveness did not correlate in either group. Whether the isolated finding of decreased glucose effectiveness could reflect an early stage in the development of the metabolic aberrations often associated with the syndrome remains to be clarified.
Enrolling traumatic brain injury (TBI) patients with an inability to provide informed consent in research is challenging. Alternatives to patient consent are not sufficiently embedded in European and ...national legislation, which allows procedural variation and bias. We aimed to quantify variations in informed consent policy and practice.
Variation was explored in the CENTER-TBI study. Policies were reported by using a questionnaire and national legislation. Data on used informed consent procedures were available for 4498 patients from 57 centres across 17 European countries.
Variation in the use of informed consent procedures was found between and within EU member states. Proxy informed consent (N = 1377;64%) was the most frequently used type of consent in the ICU, followed by patient informed consent (N = 426;20%) and deferred consent (N = 334;16%). Deferred consent was only actively used in 15 centres (26%), although it was considered valid in 47 centres (82%).
Alternatives to patient consent are essential for TBI research. While there seems to be concordance amongst national legislations, there is regional variability in institutional practices with respect to the use of different informed consent procedures. Variation could be caused by several reasons, including inconsistencies in clear legislation or knowledge of such legislation amongst researchers.
•Variation is reported in consent procedures between and within European countries.•Discordance between reported consent policy and observed practice was common.•Deferred consent was accepted in many countries, but not frequently used.•Harmonization of consent procedures is needed to improve research efficiency.•Researchers should verify and document a patients ability to provide informed consent.
We have designed an experimental technique to use on the National Ignition Facility (NIF) laser to achieve very high pressure (P sub(max) > 10 Mbar = 1000 GPa), dense states of matter at moderate ...temperatures (T < 0.5 eV = 6000 K), relevant to the core conditions of the giant planets. A discussion of the conditions in the interiors of the giant planets is given, and an experimental design that can approach those conditions is described.
The purpose of this study was to investigate the changes in structural spectral-domain optical coherence tomography (SD-OCT), OCT Angiography (OCTA) parameters, and visual acuity, 1 year after ...endoscopic endonasal approach for the removal of an intra-suprasellar pituitary adenoma compressing optic chiasm and compare outcomes with 48 hours postoperative data.
Sixteen eyes of eight patients (4 males, 4 females, mean age 52 ± 11 years) were enrolled in this prospective study. The primary outcome was to evaluate the changes over time before and after surgery, analyzing the Best Corrected Visual Acuity (BCVA), Ganglion Cell Complex (GCC), Retinal Nerve Fiber Layer (RNFL) thicknesses, the retinal vessel density (VD) of Superficial Capillary Plexus (SCP), Deep Capillary Plexus (DCP), Radial Peripapillary Capillary (RPC) and the Foveal Avascular Zone (FAZ). The secondary outcome was to identify potential biomarkers that could predict visual acuity changes after 1-year follow-up.
When comparing SD-OCT and OCTA measurements obtained after 1 year with those observed 48 hours after surgery, GCC and RNFL were significantly improved. After a significant reduction at 48 hours, GCC thickness showed a significant increase at 1 year after surgery (p = 0.007), while a significant restoration of RNFL thickness was found at 1 year (p = 0.005), as well as the VD of SCP, DCP, and RPC values. FAZ area did not change over time. BCVA significantly improved at each time after surgery (p = 0.037, p = 0.013). A statistically significant correlation was found between the preoperative BCVA, VD of SCP, DCP, RPC, and the postoperative BCVA at 1 year (p = 0.017, p = 0.029, p = 0.031, p = 0.023).
SD-OCT and OCTA provide helpful information to identify the retinal structural and vascular improvements 1 year after surgery. OCTA parameters could serve as potential predictive markers for visual acuity recovery at long-term follow-up.
Given the prevalence of alcohol use among adolescents and its negative consequences, it is important to learn more about correlates of alcohol-related problems in this population. Cigarette smoking ...appears to be associated with alcohol-related problems in adolescents. The purpose of this study was to assess cigarettes smoked per day and nicotine dependence (ND) severity as predictors of alcohol-related problems in cross-sectional models, using data from a smoking cessation clinical trial for adolescents.
Data obtained at intake were used to assess smoking-related variables as cross-sectional predictors of alcohol-related problems in models along with drinks per week and key demographics, using hierarchical multiple regression.
ND severity, as measured using the modified Fagerström Tolerance Questionnaire, significantly predicted alcohol-related problems, both when this score included and did not include an item concerning cigarettes smoked per day. A separate continuous item capturing cigarettes per day did not predict alcohol-related problems.
ND severity predicted alcohol-related problems in cross-sectional regression models, holding constant alcohol consumption and key demographics. This suggests that ND severity may be a clinical indicator of alcohol-related problems among adolescent smokers. To our knowledge, this is the first analysis of associations between smoking and alcohol involvement in a sample of adolescent smokers participating in a clinical trial.
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