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Associations of perioperative characteristics with motor function in preschool children born with esophageal atresia
No full textBackground: Children born with esophageal atresia experience long-term neurodevelopmental deficits, with unknown origin. Aims: To find associations between perioperative variables during primary esophageal atresia repair and motor function at age 5 years. Methods: This ambidirectional cohort study included children born with esophageal atresia who consecutively had been operated on in the Erasmus MC-Sophia Children's Hospital, University Medical Center, Rotterdam, from January 2007 through June 2013. The perioperative data of this cohort were collected retrospectively; the motor function data prospectively. Results: After exclusion of patients with syndromal congenital diseases (n = 8) and lost to follow-up (n = 10), the data of 53 children were included. The mean (SD) total motor function impairment z-score at 5 years of age was −0.66 (0.99), significantly below normal (p <.001). In multivariable linear regression analysis, number of postoperative days endotracheal intubation (B = −0.211, 95% CI: −0.389 to −0.033, p =.021) was negatively associated with motor outcome, whereas high blood pressure (B = 0.022, 95% CI 0.001 to 0.042, p =.038) was positively associated. Preoperative nasal oxygen supplementation versus room air (B = 0.706, 95% CI: 0.132 to 1.280, p =.016) was positively associated with motor outcome, which we cannot explain. Conclusions: Motor function in 5-year-old esophageal atresia patients was impaired and negatively associated with the number of postoperative days of endotracheal intubation and positively associated with high blood pressure. Prospective studies with critical perioperative monitoring and monitoring during stay at the intensive care unit are recommended.</p
Duplication of the IL2RA locus causes excessive IL-2 signaling and may predispose to very early onset colitis
No full textSingle genetic mutations predispose to very early onset inflammatory bowel disease (VEO-IBD). Here, we identify a de novo duplication of the 10p15.1 chromosomal region, including the IL2RA locus, in a 2-year-old girl with treatment-resistant pancolitis that was brought into remission by colectomy. Strikingly, after colectomy while the patient was in clinical remission and without medication, the peripheral blood CD4:CD8 ratio was constitutively high and CD25 expression was increased on circulating effector memory, Foxp3+, and Foxp3neg CD4+ T cells compared to healthy controls. This high CD25 expression increased IL-2 signaling, potentiating CD4+ T-cell-derived IFNγ secretion after T-cell receptor (TCR) stimulation. Restoring CD25 expression using the JAK1/3-inhibitor tofacitinib controlled TCR-induced IFNγ secretion in vitro. As diseased colonic tissue, but not the unaffected duodenum, contained mainly CD4+ T cells with a prominent IFNγ-signature, we hypothesize that local microbial stimulation may have initiated colonic disease. Overall, we identify that duplication of the IL2RA locus can associate with VEO-IBD and suggest that increased IL-2 signaling predisposes to colonic intestinal inflammation.</p
Measures for the betterment of the labor market position of non-standard working regimes in the cultural and creative sector in the Netherlands
No full textThis article reflects on possible effects on income and earning capacity of creative workers of three measures that were recently introduced or that are being discussed to combat the vulnerability of non-standard working conditions in the cultural and creative sector in the Netherlands: the Balanced Labor Market Act, the Fair Practice Code for Culture, and a call for certain unified agreements, for instance in the form of minimum tariffs for self-employed workers. Each of these measures separately has its merits and the intention to improve working conditions. Therefore, the power lies in their joint introduction, which combines general legislation with a moral benchmark and subsector-specific solutions. However, in this combination several unintended consequences loom, such as the possible separation between professional and amateur creative workers, a higher threshold for talent to enter the sector, threats to artistic and aesthetic innovation, and the prioritization of fairness over equality.</p
Drug transport kinetics of intravascular triggered drug delivery systems
No full textIntravascular triggered drug delivery systems (IV-DDS) for local drug delivery include various stimuli-responsive nanoparticles that release the associated agent in response to internal (e.g., pH, enzymes) or external stimuli (e.g., temperature, light, ultrasound, electromagnetic fields, X-rays). We developed a computational model to simulate IV-DDS drug delivery, for which we quantified all model parameters in vivo in rodent tumors. The model was validated via quantitative intravital microscopy studies with unencapsulated fluorescent dye, and with two formulations of temperature-sensitive liposomes (slow, and fast release) encapsulating a fluorescent dye as example IV-DDS. Tumor intra- and extravascular dye concentration dynamics were extracted from the intravital microscopy data by quantitative image processing, and were compared to computer model results. Via this computer model we explain IV-DDS delivery kinetics and identify parameters of IV-DDS, of drug, and of target tissue for optimal delivery. Two parameter ratios were identified that exclusively dictate how much drug can be delivered with IV-DDS, indicating the importance of IV-DDS with fast drug release (~sec) and choice of a drug with rapid tissue uptake (i.e., high first-pass extraction fraction). The computational model thus enables engineering of improved future IV-DDS based on tissue parameters that can be quantified by imaging.</p
Sustainability integration for sovereign debt investors
No full textInvestors recently adopted a novel approach to sustainable investing: engaging with countries to advance sustainable development. But engaging with sovereign entities on sustainability challenges, like the Sustainable Development Goals (SDGs), is complex. To guide sovereign debt investors in operationalizing this new sustainable investing strategy, this methodology and policy paper creates a framework that navigates the sovereign engagement process. The framework answers three questions: (i) who to engage with; (ii) what to engage on; and (iii) how to engage. First, countries are prioritized based on the investor's investment exposure and the country's progress on the SDGs. Second, using public data, SDGs and sub-targets are identified that face slow progress, thus being priorities to engage on. Third, a detailed roadmap is provided that offers a systematic approach to engaging with the identified country on selected SDG(s). This sovereign SDG Engagement Framework aims to help investors and countries achieve their shared sustainability objectives.</p
BRCA2 binding through a cryptic repeated motif to HSF2BP oligomers does not impact meiotic recombination
No full textBRCA2 and its interactors are required for meiotic homologous recombination (HR) and fertility. Loss of HSF2BP, a BRCA2 interactor, disrupts HR during spermatogenesis. We test the model postulating that HSF2BP localizes BRCA2 to meiotic HR sites, by solving the crystal structure of the BRCA2 fragment in complex with dimeric armadillo domain (ARM) of HSF2BP and disrupting this interaction in a mouse model. This reveals a repeated 23 amino acid motif in BRCA2, each binding the same conserved surface of one ARM domain. In the complex, two BRCA2 fragments hold together two ARM dimers, through a large interface responsible for the nanomolar affinity — the strongest interaction involving BRCA2 measured so far. Deleting exon 12, encoding the first repeat, from mBrca2 disrupts BRCA2 binding to HSF2BP, but does not phenocopy HSF2BP loss. Thus, results herein suggest that the high-affinity oligomerization-inducing BRCA2-HSF2BP interaction is not required for RAD51 and DMC1 recombinase localization in meiotic HR.</p
Changing Inequalities in Health-Adjusted Life Expectancy by Income and Race in South Africa
No full textTrends in socioeconomic-related health inequalities is a particularly pertinent topic in South Africa where years of systematic discrimination under apartheid bequeathed a legacy of inequalities in health outcomes. We use three nationally representative datasets to examine trends in income- and race-related inequalities in life expectancy (LE) and health-adjusted life expectancy (HALE) since the beginning of the millennium. We find that, in aggregate, (HA)LE at age five fell substantially between 2001 and 2007, but then increased to above 2001 levels by 2016, with the largest changes observed among prime age adults. Income- and race-related inequalities in both LE and HALE favor relatively well-off and non-Black South Africans in all survey years. Both income- and race-related inequalities in (HA)LE grew between 2001 and 2007, and then narrowed between 2007 to 2016. However, while race-related inequalities in (HA)LE in 2016 were smaller than in 2001, income-related inequalities in (HA)LE were greater in 2016 than in 2001. Based on the patterns and timing observed, these trends in income- and race-related inequalities in (HA)LE are most likely related to the delayed initial policy response to the HIV epidemic, the subsequent rapid and effective rollout of anti-retroviral therapy, and the changes in the overall income distribution among Black South Africans. In particular, the growth of the Black middle class narrowed the HA(LE) gap with the non-Black population but reinforced income-related inequalities.</p
Are behavioral and electrophysiological measures of impulsivity useful for predicting entrepreneurship?
No full textWe examine the association between several behavioral and electrophysiological indices of impulsivity-related constructs and multiple entrepreneurial constructs. Specifically, we investigate if these behavioral and electrophysiological measures are more useful as predictors of entrepreneurship than self-reported measures of impulsivity. Our findings are based on two datasets (n = 133 and n = 142) and indicate that behavioral and electrophysiological impulsivity measures are not robustly associated with entrepreneurship constructs, in contrast to self-reported measures of impulsivity. Though disappointing at first, our findings pave the way for future research on the relevance of behavioral and electrophysiological measures for entrepreneurship.</p
Cystic pancreatic lesions
No full textCystic pancreatic lesions (CPLs) are frequently casual findings in radiological examinations performed for other reasons in patients with unrelated symptoms. As they require different management according to their histological nature, differential diagnosis is essential. Radiologist plays a key role in the diagnosis and management of these lesions as imaging is able to correctly characterize most of them and thus address to a correct management. The first step for a correct characterization is to look for a communication between the CPLs and the main pancreatic duct, and then, it is essential to evaluate the morphology of the lesions. Age, sex and a history of previous pancreatic pathologies are important information to be used in the differential diagnosis. As some CPLs with different pathologic backgrounds can show the same morphological findings, differential diagnosis can be difficult, and thus, the final diagnosis can require other techniques, such as endoscopic ultrasound, endoscopic ultrasound-fine needle aspiration and endoscopic ultrasound-through the needle biopsy, and multidisciplinary management is important for a correct management.</p
Effect of intensive care unit-specific virtual reality (ICU-VR) to improve psychological well-being and quality of life in COVID-19 ICU survivors
No full textBackground: The SARS-CoV-2 outbreak has resulted in a tremendous increase in hospital and intensive care unit (ICU) admissions all over the world. Patients with severe coronavirus disease 2019 (COVID-19) warranting ICU treatment usually have prolonged mechanical ventilation and are expected to be prone to develop psychological impairments, such as post-traumatic stress disorder (PTSD), anxiety and depression, which negatively impact quality of life. To date, no effective treatment strategy is available. In the current trial, we aim to assess the effect of an ICU-specific virtual reality (ICU-VR) intervention on psychological well-being and quality of life after COVID-19 ICU treatment. Methods: In this multicentre, randomized controlled trial, we aim to examine whether COVID-19-specific ICU-VR, offered 3 months after hospital discharge, improves psychological well-being and quality of life. Secondary objectives are, firstly, to examine the intra-group changes in psychological well-being and quality of life and the inter-group differences in psychological well-being and quality of life during follow-up, up to 12 months after hospital discharge, and secondly, to examine patients’ satisfaction with and rating of ICU care and aftercare and patients’ perspectives on ICU-VR. Eighty adult patients treated for COVID-19 in the mixed-surgical ICUs of four hospitals in Rotterdam, the Netherlands, will be included and randomized (1:1) to either early or late ICU-VR between June 29 and December 31, 2020. Patients randomized to early ICU-VR will receive the ICU-VR intervention during an outpatient clinic visit 3 months after hospital discharge, whereas patients randomized to late ICU-VR will receive ICU-VR 6 months after hospital discharge. Primary outcomes of this study are psychological well-being, assessed using the Impact of Event Scale–Revised (IES-R) and the Hospital Anxiety and Depression Scale (HADS), and quality of life, assessed using the European Quality of Life 5 Dimensions (EQ-5D) and RAND-36 questionnaires, up to 6 months after hospital discharge. Discussion: Currently, an effective treatment for psychological sequelae after ICU treatment for specific illnesses is unavailable. Results from this study will provide insight whether virtual reality is a modality that can be used in ICU aftercare to improve psychological well-being and quality of life, or satisfaction, after ICU treatment for specific illnesses such as COVID-19. Trial registration: This trial has been retrospectively registered on the Netherlands Trial Register on August 14, 2020 (NL8835).</p