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Hypoplastic left heart syndrome (HLHS) is a relatively rare severe congenital heart defect (CHD) closely linked to other left ventricular outflow tract (LVOT) lesions including bicuspid aortic valve (BAV), one of the most common heart defects. While HLHS, BAV, and other LVOT lesions have a strong genetic underpinning, their genetic etiology remains poorly understood. Findings from a large-scale mouse mutagenesis screen showed HLHS has a multigenic etiology and is genetically heterogenous, explaining difficulties in identifying the genetic causes of HLHS. In Ohia mice, HLHS shows incomplete penetrance. Some mice exhibited small LV with normal aorta, and others a normal LV with hypoplastic aorta, indicating the LV hypoplasia is not hemodynamically driven. In Ohia mutants, HLHS was found to have a digenic modular construction, with mutation in a chromatin modifier causing the small LV phenotype and mutation in Pcdha9 causing the aorta/aortic valve hypoplasia. The Pcdha9 mutation alone can cause BAV, and in the human genome two common deletion copy number variants spanning PCDHA7-10 are associated with BAV. Hence the digenic etiology of HLHS can account for the close association of HLHS, a rare CHD, with BAV, one of the most common CHD. Functional analysis of Ohia HLHS heart tissue showed severe mitochondrial dysfunction in the small LV, while the normal size RV is also affected but milder, suggesting possible role in vulnerability of surgically palliated HLHS patients to heart failure. These findings suggest insights into the genetics of HLHS may yield new therapies for improving outcome for patients with HLHS.

Background: Perfluoroalkyl substances (PFAS) are man-made fluorinated chemicals, widely used in various types of consumer products, resulting in their omnipresence in human populations. The aim of this study was to describe current PFAS levels in European teenagers and to investigate the determinants of serum/plasma con-centrations in this specific age group.Methods: PFAS concentrations were determined in serum or plasma samples from 1957 teenagers (12-18 years) from 9 European countries as part of the HBM4EU aligned studies (2014-2021). Questionnaire data were post -harmonized by each study and quality checked centrally. Only PFAS with an overall quantification frequency of at least 60% (PFOS, PFOA, PFHxS and PFNA) were included in the analyses. Sociodemographic and lifestyle factors were analysed together with food consumption frequencies to identify determinants of PFAS exposure. The variables study, sex and the highest educational level of household were included as fixed factors in the multivariable linear regression models for all PFAS and each dietary variable was added to the fixed model one by one and for each PFAS separately.Results: The European exposure values for PFAS were reported as geometric means with 95% confidence intervals (CI): PFOS [2.13 mu g/L (1.63-2.78)], PFOA ([0.97 mu g/L (0.75-1.26)]), PFNA [0.30 mu g/L (0.19-0.45)] and PFHxS [0.41 mu g/L (0.33-0.52)]. The estimated geometric mean exposure levels were significantly higher in the North and West versus the South and East of Europe. Boys had significantly higher concentrations of the four PFAS compared to girls and significantly higher PFASs concentrations were found in teenagers from households with a higher education level. Consumption of seafood and fish at least 2 times per week was significantly associated with 21% (95% CI: 12-31%) increase in PFOS concentrations and 20% (95% CI: 10-31%) increase in PFNA concentrations as compared to less frequent consumption of seafood and fish. The same trend was observed for PFOA and PFHxS but not statistically significant. Consumption of eggs at least 2 times per week was associated with 11% (95% CI: 2-22%) and 14% (95% CI: 2-27%) increase in PFOS and PFNA concentrations, respectively, as compared to less frequent consumption of eggs. Significantly higher PFOS concentrations were observed for participants consuming offal (14% (95% CI: 3-26%)), the same trend was observed for the other PFAS but not statistically significant. Local food consumption at least 2 times per week was associated with 40% (95% CI: 19-64%) increase in PFOS levels as compared to those consuming local food less frequently.Conclusion: This work provides information about current levels of PFAS in European teenagers and potential dietary sources of exposure to PFAS in European teenagers. These results can be of use for targeted monitoring of PFAS in food. This work was supported by the European Union’s Horizon 2020 research and innovation programme under Grant agreement No 733032 HBM4EU (www.HBM4EU.eu), and received co-funding from the authors’ organizations: Riksmaten Adolescents: Riksmaten Adolescents was performed by the Swedish Food Agency with financial support from the Swedish Environmental Protection Agency and the Swedish Civil Contingencies Agency. NEB II: The Norwegian Institute of Public Health (NIPH) has contributed to funding of the Norwegian Environmental Biobank (NEB). The laboratory measurements have partly been funded by the Research Council of Norway through research projects (275903 and 268465) PCB cohort follow-up: PCB cohort follow-up received additional funding from the Ministry of Health of the Slovak Republic, program 07B0103. BEA: BEA study was funded by the Spanish Ministry of Agriculture, Fisheries and Food and the Instituto de Salud Carlos III (SEG 1321/15) SLO-CRP: The Slovenian SLO-CRP study was co-financed by the Joˇzef Stefan Institute program P1- 0143, and a national project “Exposure of children and adolescents to selected chemicals through their habitat environment” (grant agreement No. C2715-16-634802). CROME: CROME study was co-funded by the European Commission research funds of Horizon 2020. ESTEBAN: ESTEBAN study was funded by Sant´e Publique France and the French ministries of Health and the Environment. GerES V-sub: The funding of the German Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection is gratefully acknowledged. FLEHS IV: The Flemish Center of Expertise on Environment and Health is funded by the Government of Flanders, Department of Environment & Spatial Development. We are grateful to all teenagers and their families that participated in the studies. HBM4EU is co-financed under Horizon 2020 (grant agreement No 733032). FLEHS: We thank the field workers from the Provincial Institute of Hygiene and VITO for the sample and data collection. All collaborators of the scientific teams of the Flemish Center of Expertise on Environment and Health (https://www.milieu-en-gezondheid.be/en/about-the-cente r-0) and Karen Van Campenhout and Caroline Teughels from the Flemish Department of Environment & Spatial Development for their valuable input in the field work committee. Riksmaten Adolescents: Personnel from the regional Occupational and Environmental Medicine Divisions in Gothenburg, Linkoping, ¨ Lund, Stockholm, and Umeå are acknowledged for help with blood sampling. Jonathan P. Benskin and colleagues at the Department of Environmental Science and Analytical Chemistry, Stockholm University are acknowledged for the chemical analyses. PCB cohort follow-up: We wish to thank Dana Jureˇckova, ´ MD, PhD, head of Department of Pediatrics, hospital “Svet zdravia”, Michalovce and her personnel for blood sampling, questionnaire administration and examination of adolescents, personnel from the laboratory of biochemistry and haematology (AlphaMedical) in Michalovce, Slovakia, for blood samples processing and colleagues from RECETOX, Masaryk University, Brno, Czech Republic, for chemical analyses.

The necessiey of physical social diseancing, broughe aboue by ehe pandemic of Covid-19, raised problems ehae were previously mieigaeed by precarious coneace in regions ehae were already experiencing some isolaeion. The objeceive of ehis areicle is eo: ideneify ehe relaeionship beeween eeachers and ehe pedagogical knowledge in ehe conseruceion of aleernaeives ways for ehe coneinuiey of ehe eeaching and learning process in riverside educaeion. In order eo carry oue ehe exploraeory research, ehe produceion of empirical daea eook place ae ehe Jose Sobreira do Nascimeneo Municipal School, locaeed in ehe Faeima Communiey, in Rio Negro-Amazonas. A eeacher, parenes and seudenes from ehe 6eh grade and of ehe Youeh and Adule Educaeion-EJA pareicipaeed in ehis seudy. The WhaesApp inseane communicaeor was used as inserumene. The inieial refleceions revealed ehe eechnological issues, experienced in ehe riverside educaeional coneexe and how ehe pedagogical knowledge, coneemplaeing eeachers and seudenes, are in conseane conseruceion, providing opporeunieies for learning ehae are consiseene wieh ehe seudenes' realiey. © 2021 UNIVERSIDADE FEEVALEÂ . All Rights Reserved.

ObjectiveTerm congenital heart disease (CHD) neonates display abnormalities of brain structure and maturation, which are possibly related to underlying patient factors, abnormal physiology and perioperative insults. Our primary goal was to delineate associations between clinical factors and postnatal brain microstructure in term CHD neonates using diffusion tensor imaging (DTI) magnetic resonance (MR) acquisition combined with complementary data-driven connectome and seed-based tractography quantitative analyses. Our secondary goal was to delineate associations between mild dysplastic structural brain abnormalities and connectome and seed-base tractography quantitative analyses. These mild dysplastic structural abnormalities have been derived from prior human infant CHD MR studies and neonatal mouse models of CHD that were collectively used to calculate to calculate a brain dysplasia score (BDS) that included assessment of subcortical structures including the olfactory bulb, the cerebellum and the hippocampus.MethodsNeonates undergoing cardiac surgery for CHD were prospectively recruited from two large centers. Both pre- and postoperative MR brain scans were obtained. DTI in 42 directions was segmented into 90 regions using a neonatal brain template and three weighted methods. Clinical data collection included 18 patient-specific and 9 preoperative variables associated with preoperative scan and 6 intraoperative (e.g., cardiopulmonary bypass and deep hypothermic circulatory arrest times) and 12 postoperative variables associated with postoperative scan. We compared patient specific and preoperative clinical factors to network topology and tractography alterations on a preoperative neonatal brain MRI, and intra and postoperative clinical factors to network topology alterations on postoperative neonatal brain MRI. A composite BDS was created to score abnormal findings involving the cerebellar hemispheres and vermis, supratentorial extra-axial fluid, olfactory bulbs and sulci, hippocampus, choroid plexus, corpus callosum, and brainstem. The neuroimaging outcomes of this study included (1) connectome metrics: cost (number of connections) and global/nodal efficiency (network integration); (2) seed based tractography methods of fractional anisotropy (FA), radial diffusivity, and axial diffusivity. Statistics consisted of multiple regression with false discovery rate correction (FDR) comparing the clinical risk factors and BDS (including subcortical components) as predictors/exposures and the global connectome metrics, nodal efficiency, and seed based- tractography (FA, radial diffusivity, and axial diffusivity) as neuroimaging outcome measures.ResultsA total of 133 term neonates with complex CHD were prospectively enrolled and 110 had analyzable DTI. Multiple patient-specific factors including d-transposition of the great arteries (d-TGA) physiology and severity of impairment of fetal cerebral substrate delivery (i.e., how much the CHD lesion alters typical fetal circulation such that the highest oxygen and nutrient rich blood from the placenta are not directed toward the fetal brain) were predictive of preoperative reduced cost (p < 0.0073) and reduced global/nodal efficiency (p < 0.03). Cardiopulmonary bypass time predicted postoperative reduced cost (p < 0.04) and multiple postoperative factors [extracorporeal membrane oxygenation (ECMO), seizures and cardiopulmonary resuscitation (CPR)] were predictive of postoperative reduced cost and reduced global/nodal efficiency (p < 0.05). Anthropometric measurements (weight, length, and head size) predicted tractography outcomes. Total BDS was not predictive of brain network topology. However, key subcortical components of the BDS score did predict key global and nodal network topology: abnormalities of the cerebellum predicted reduced cost (p < 0.0417) and of the hippocampus predicted reduced global efficiency (p < 0.0126). All three subcortical structures predicted unique alterations of nodal efficiency (p < 0.05), including hippocampal abnormalities predicting widespread reduced nodal efficiency in all lobes of the brain, cerebellar abnormalities predicting increased prefrontal nodal efficiency, and olfactory bulb abnormalities predicting posterior parietal-occipital nodal efficiency.ConclusionPatient-specific (d-TGA anatomy, preoperative impairment of fetal cerebral substrate delivery) and postoperative (e.g., seizures, need for ECMO, or CPR) clinical factors were most predictive of diffuse postnatal microstructural dysmaturation in term CHD neonates. Anthropometric measurements (weight, length, and head size) predicted tractography outcomes. In contrast, subcortical components (cerebellum, hippocampus, olfactory) of a structurally based BDS (derived from CHD mouse mutants), predicted more localized and regional postnatal microstructural differences. Collectively, these findings suggest that brain DTI connectome and seed-based tractography are complementary techniques which may facilitate deciphering the mechanistic relative contribution of clinical and genetic risk factors related to poor neurodevelopmental outcomes in CHD.

Urban flooding is a major challenge for many megacities in low-elevation coastal zones (LECZs), especially in Southeast Asia. In these regions, the effects of environmental stressors overlap with rapid urbanization, which significantly aggravates the hazard potential. Ho Chi Minh City (HCMC) in southern Vietnam is a prime example of this set of problems and therefore a suitable case study to apply the concept of low-regret disaster risk adaptation as defined by the Intergovernmental Panel on Climate Change (IPCC). In order to explore and evaluate potential options of hazard mitigation, a hydro-numerical model was employed to scrutinize the effectiveness of two adaptation strategies: (1) a classic flood protection scheme including a large-scale ring dike as currently constructed in HCMC and (2) the widespread installation of small-scale rainwater detention as envisioned in the framework of the Chinese Sponge City Program (SCP). A third adaptation scenario (3) assesses the combination of both approaches (1) and (2). From a hydrological point of view, the reduction in various flood intensity proxies that were computed within this study suggests that large-scale flood protection is comparable but slightly more effective than small-scale rainwater storage: for instance, the two adaptation options could reduce the normalized flood severity index (INFS), which is a measure combining flood depth and duration, by 17.9 % and 17.7 %, respectively. The number of flood-prone manufacturing firms that would be protected after adaptation, in turn, is nearly 2 times higher for the ring dike than for the Sponge City approach. However, the numerical results also reveal that both response options can be implemented in parallel, not only without reducing their individual effectiveness but also complementarily with considerable added value. Additionally, from a governance perspective, decentralized rainwater storage conforms ideally to the low-regret paradigm: while the existing large-scale ring dike depends on a binary commitment (to build or not to build), decentralized small- and micro-scale solutions can be implemented gradually (for example through targeted subsidies) and add technical redundancy to the overall system. In the end, both strategies are highly complementary in their spatial and temporal reduction in flood intensity. Local decision-makers may hence specifically seek combined strategies, adding to singular approaches, and design multi-faceted adaptation pathways in order to successfully prepare for a deeply uncertain future.

The recent health crisis experienced by all nations in the world created detrimental change in the countenance of educational sector especially in the new mode of delivering the instructions as measure in containing the virus and as well as continuing education. In the works of literature, little to no attention was given to the formulation of the most essential learning competencies (MELCs) as strategic measure for modular learning. This paves the way to probe the lived experiences of the teachers pertaining to the compromised competencies under MELCs. Anchoring to the Sociocultural Theory of Cognitive Development by Vgotsky, this study utilized Interpretative Phenomenological Research Design with Interpretative Phenomenological Analysis (IPA) popularized by Moustakas and modified by Van Kaam as approach to analyzed the transcripts. Using purposive sampling, there were 7 informants participated the study. They are all qualified according to the inclusion criteria set by the study. The study generated three themes which are: The Compromised, The Cut-short, and The Champion. These themes elaborated the lived experiences of the teachers using the Most Essential Learning Competencies forwarded to the students. It is recommended that the learning support should be magnified in the new learning modality. Hence, the Most Essential Learning Competencies will be not be compromised.

Background Effective contact tracing, vaccination, and isolation of cases of SARS-CoV-2 infection and their high-risk contacts constituted measures to contain the spread of COVID-19. In Portugal, in October 2021, low-risk cohabitants were lifted the obligation to isolate. The aim of this study was to estimate the relative risk of infection for close contacts, regarding the type of close contact and being cohabitants. Methods A descriptive longitudinal study, with an analytical component was performed. Sociodemographic and epidemiologic data from close contacts and confirmed cases in Loures and Odivelas, between October and November 2021, was collected from a regional database and from Trace COVID-19 platform. We performed a descriptive analysis and estimated the relative risk of SARS-CoV-2 positive test, stratified by type of contact and cohabitation, with 95% confidence level. Results We identified 200 confirmed cases and 428 people who were close contacts, corresponding to 502 different close contacts (59 people had contact with more than a case). From 502 close contacts, 268 were classified as low-risk and 230 as high-risk. Full time cohabitation was present in 310 of close contacts. Between contact tracing day and the next 4 weeks, 58 (10.9%) of close contacts tested positive. Risk of high-risk contacts testing positive was 2.7 [1.5-4.6], compared with low-risk contacts. Risk of cohabitants testing positive was 3.5 [1.6-7.7], compared with non-cohabitants. Risk of a high-risk cohabitant testing positive was 2.2 [1.1-4.4], compared with low-risk cohabitants. There was no higher risk of high-risk cohabitants testing positive compared with high-risk non-cohabitants. Same was true for low-risk cohabitants and non-cohabitants. Conclusions These results allow us to understand how to better stratify close contacts and apply isolation measures, according to the risk of testing positive. Further studies should be developed to assess the impact of other variables. Key messages • We identified an increased risk of testing positive in high-risk contacts, and in cohabitants. • Cohabitants could be stratified regarding being high or low-risk, with different measures being applied.

The pig is an ideal model system for studying human development and disease due to its similarities to human anatomy, physiology, size, and genome. Further, advances in CRISPR gene editing have made genetically engineered pigs viable models for the study of human pathologies and congenital anomalies. However, a detailed atlas illustrating pig development is necessary for identifying and modeling developmental defects. Here we describe normal development of the pig abdominal system and show examples of congenital defects that can arise in CRISPR gene edited SAP130 mutant pigs. Normal pigs at different gestational ages from day 20 (D20) to term were examined and the configuration of the abdominal organs was studied using 3D histological reconstructions with episcopic confocal microscopy, magnetic resonance imaging (MRI) and necropsy. This revealed prominent mesonephros, a transient embryonic organ present only during embryogenesis, at D20, while the developing metanephros that will form the permanent kidney are noted at D26. By D64 the mesonephroi are absent and only the metanephroi remain. The formation of the liver and pancreas was observed by D20 and complete by D30 and D35 respectively. The spleen and adrenal glands are first identified at D26 and completed by D42. The developing bowel and the gonads are identified at D20. The bowel appears completely rotated by D42, and testes in the male were descended at D64. This atlas and the methods used are excellent tools for identifying developmental pathologies of the abdominal organs in the pig at different stages of development.

A significant gap exists in our understanding and ability to predict the spatial occurrence and extent of rare earth elements (REE) and certain critical minerals (CM) in sedimentary strata. This is largely due to a lack of existing, systematic, and well-distributed REE and CM samples and analyses in United States sedimentary basins. In addition, the type of sampling and characterization performed to date has generally lacked the resolution and approach required to constrain geologic and geographic heterogeneities typical of subsurface, mineral resources. Here, we describe a robust and systematic method for collecting core scale characterization data that can be applied to studies on the contextual and spatial attributes, the geologic history, and lithostratigraphy of sedimentary basins. The methods were developed using drilled cores from coal bearing sedimentary strata in the Powder River Basin, Wyoming (PRB). The goal of this effort is to create a unified core characterization methodology to guide systematic collection of key data to achieve a foundation of spatially and geologically constrained REEs and CMs. This guidance covers a range of measurement types and methods that are each useful either individually or in combination to support characterization and delineation of REE and CM occurrences. The methods herein, whether used in part or in full, establish a framework to guide consistent acquisition of geological, geochemical, and geospatial datasets that are key to assessing and validating REE and CM occurrences from geologic sources to support future exploration, assessment, and techno-economic related models and analyses.

Deep brain stimulation (DBS) is indisputable in improving motor symptoms of Parkinson's Disease (PD) and X-Linked Dystonia Parkinsonism (XDP)(4,9,22,23,26). However, a discrepancy between this improvement and the perceived quality of life (QoL) has been observed. This study aims to investigate changes and correlation between quality of life, motor symptoms and medication dosing.This prospective observational study enrolled 13 patients (6 PD, 7 XDP) who underwent DBS from 2017 to 2018. Quality of life changes were determined by Parkinson's Disease - 39 (PDQ-39 English and Filipino versions) at baseline, 6 months and 12 month after DBS. Motor symptoms and medication dosing were also evaluated within the same period and correlated with QoL changes.There is a significant reduction of PDQ-39 mean scores[F(1.06,11.64) = 18.235; p = 0.001; ηp2 = 0.624] between baseline and 6 months among XDP patients (p = 0.018) and baseline and 12 months among PD patients (p = 0.027) and XDP patients (p 0.001). Specific domains with significant improvement were stigma, cognition, mobility, ADLs, communication and bodily discomfort. Correlating these with changes in motor symptoms, only mobility for PD and ADLs for XDP were positively related.This study has shown the positive impact of DBS in improving QoL among PD and XDP patients over a 12-month period.