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Hyperglycemia-induced pathological microglial responses and subsequent neuronal damage are notable characteristics of diabetes-associated cognitive impairment (DACI). Cholesterol accumulation in the brain is a prevalent consequence of diabetes mellitus (DM), exacerbating pathological microglial responses. Regarding disordered glucose and lipid metabolism, the Sterol Regulatory Element-Binding Protein (SREBP) cleavage-activating protein (SCAP), a cholesterol sensor, exhibits increased expression and abnormal translocation from the endoplasmic reticulum to the Golgi, amplifying the inflammatory response. Therefore, we hypothesized that overexpression of microglia-SCAP and cholesterol accumulation in DM mice could induce pathological microglial responses associated with DACI. Our type 2 DM mice model presented an abnormal increase in microglial SCAP expression. The functional loss of microglia-specific SCAP in DM mice improved cognitive impairment, neuronal synaptic plasticity deficits, and abnormal microglial responses. Mechanistically, the accumulated SCAP directly bound to and enhanced the activation of the microglial-specific inflammatory amplifier, NLRP3 inflammasome, in Golgi, thereby increasing pathological microglial responses and promoting neuronal damage. These findings indicate an important regulatory axis of microglial responses from SCAP to the NLRP3 inflammasome pathway in microglia. These underscore the crosstalk between cholesterol disorders and pathological microglial responses, offering a promising avenue for pharmaceutical interventions in DACI.
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Disfunção Cognitiva , Inflamassomos , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana , Camundongos Endogâmicos C57BL , Microglia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Doenças Neuroinflamatórias , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Microglia/metabolismo , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/etiologia , Camundongos , Inflamassomos/metabolismo , Doenças Neuroinflamatórias/metabolismo , Proteínas de Membrana/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Colesterol/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/complicações , Plasticidade Neuronal , Neurônios/metabolismo , Encéfalo/metabolismoRESUMO
PURPOSE: The study aimed to investigate the potential effect of Antithrombin III (ATIII) between chronic renal insufficiency and chronic coronary artery disease (chronic CAD) in type 2 diabetes mellitus (T2DM) patients. METHODS: T2DM patients hospitalized in ZhongDa Hospital from 2013 to 2018 were enrolled. Relationships between renal function, ATIII, and chronic CAD risk were explored using multivariate regression models. Multiplicative and additive interactions were investigated between ATIII and renal function for CAD risk, and the role of ATIII was determined by bootstrap mediation analysis in patients with chronic renal dysfunction. RESULTS: A total of 4197 patients were included in the study, with a chronic CAD prevalence of 23.02%. Low ATIII level was statistically associated with chronic renal insufficiency and elevated CAD risk even after adjustments (P < 0.05). A positive correlation between renal function and ATIII was demonstrated, and each 1 SD increase in renal function, ATIII increased by 2.947% (2.406-3.488%, P < 0.001) and 0.969% (0.297-1.642%, P < 0.001) in crude and adjusted models respectively. Patients with decreased renal function and ATIII were at the highest chronic CAD risk (OR = 1.51, 95%CI:1.15-1.98, P < 0.05), while no multiplicative and additive interaction effects were significant. Bootstrap mediation analysis estimated that ATIII mediated approximately 4.27% of the effect of chronic renal insufficiency on chronic CAD risk. CONCLUSION: ATIII may serve as a mediator between chronic renal insufficiency and chronic CAD, providing mechanistic clues for renal-heart association and new insight into clinical therapies.
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Antitrombina III , Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/sangue , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Idoso , Fatores de RiscoRESUMO
Aimed at beta spectrometry and dosimetry for mixed beta-gamma fields, a Si-plastic scintillator coincidence beta-ray spectrometer has been developed. The spectrometer collects pure beta-ray spectra by rejecting the gamma-ray detection events through coincidence. Both pulse height and arrival time of each detection event were recorded in list mode by a compact digital processing system. Spectral measurements were carried out using mixed beta-gamma fields from 90Sr/90Y and 137Cs sources for various beta and gamma count rates to evaluate the system performance. Coincidence beta spectra were collected for four fixed beta count rates (7.3-241 cps) from 90Sr/90Y while the gamma count rate from 137Cs was varied from 500 to 8000 cps. The coincidence beta spectrum was stable and unperturbed by the gamma detection events for most measurements while notable perturbation was observed in the low energy region when the beta to gamma count ratio is very low.
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BACKGROUND: Identifying high-risk individuals is crucial for preventing cardiovascular diseases (CVDs). Currently, risk assessment is mostly performed by physicians. Mobile health apps could help decouple the determination of risk from medical resources by allowing unrestricted self-assessment. The respective test results need to be interpretable for laypersons. OBJECTIVE: Together with a patient organization, we aimed to design a digital risk calculator that allows people to individually assess and optimize their CVD risk. The risk calculator was integrated into the mobile health app HerzFit, which provides the respective background information. METHODS: To cover a broad spectrum of individuals for both primary and secondary prevention, we integrated the respective scores (Framingham 10-year CVD, Systematic Coronary Risk Evaluation 2, Systematic Coronary Risk Evaluation 2 in Older Persons, and Secondary Manifestations Of Arterial Disease) into a single risk calculator that was recalibrated for the German population. In primary prevention, an individual's heart age is estimated, which gives the user an easy-to-understand metric for assessing cardiac health. For secondary prevention, the risk of recurrence was assessed. In addition, a comparison of expected to mean and optimal risk levels was determined. The risk calculator is available free of charge. Data safety is ensured by processing the data locally on the users' smartphones. RESULTS: Offering a risk calculator to the general population requires the use of multiple instruments, as each provides only a limited spectrum in terms of age and risk distribution. The integration of 4 internationally recommended scores allows risk calculation in individuals aged 30 to 90 years with and without CVD. Such integration requires recalibration and harmonization to provide consistent and plausible estimates. In the first 14 months after the launch, the HerzFit calculator was downloaded more than 96,000 times, indicating great demand. Public information campaigns proved effective in publicizing the risk calculator and contributed significantly to download numbers. CONCLUSIONS: The HerzFit calculator provides CVD risk assessment for the general population. The public demonstrated great demand for such a risk calculator as it was downloaded up to 10,000 times per month, depending on campaigns creating awareness for the instrument.
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The Cryogenian Sturtian and Marinoan Snowball Earth glaciations bracket a nonglacial interval during which Demosponge and green-algal biomarkers first appear. To understand the relationships between environmental perturbations and early animal evolution, we measured sulfur and mercury isotopes from the Datangpo Formation from South China. Hg enrichment with positive Δ199Hg excursion suggests enhanced volcanism, potentially due to depressurization of terrestrial magma chambers during deglaciation. A thick stratigraphic interval of negative Δ33Spy indicates that the nonglacial interlude was characterized by low but rising sulfate levels. Model results reveal a mechanism to produce the Δ33S anomalies down to -0.284 through Rayleigh distillation. We propose that extreme temperatures and anoxia contributed to the apparent delay in green algal production in the aftermath of the Sturtian glaciation and the subsequent reoxygenation of the iron-rich and sulfate-depleted ocean paved the way for evolution of animals.
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The Ediacaran Period (~635-539 Ma) is marked by the emergence and diversification of complex metazoans linked to ocean redox changes, but the processes and mechanism of the redox evolution in the Ediacaran ocean are intensely debated. Here we use mercury isotope compositions from multiple black shale sections of the Doushantuo Formation in South China to reconstruct Ediacaran oceanic redox conditions. Mercury isotopes show compelling evidence for recurrent and spatially dynamic photic zone euxinia (PZE) on the continental margin of South China during time intervals coincident with previously identified ocean oxygenation events. We suggest that PZE was driven by increased availability of sulfate and nutrients from a transiently oxygenated ocean, but PZE may have also initiated negative feedbacks that inhibited oxygen production by promoting anoxygenic photosynthesis and limiting the habitable space for eukaryotes, hence abating the long-term rise of oxygen and restricting the Ediacaran expansion of macroscopic oxygen-demanding animals.
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Sedimentos Geológicos , Água do Mar , Animais , Fósseis , Oceanos e Mares , Oxigênio/análise , Evolução BiológicaRESUMO
Pollutant emissions from coal fires have caused serious concerns in major coal-producing countries. Great efforts have been devoted to suppressing them in China, notably at the notorious Wuda Coalfield in Inner Mongolia. Recent surveys revealed that while fires in this coalfield have been nearly extinguished near the surface, they persist underground. However, the impacts of Hg volatilized from underground coal fires remain unclear. Here, we measured concentrations and isotope compositions of atmospheric Hg in both gaseous and particulate phases at an urban site near the Wuda Coalfield. The atmospheric Hg displayed strong seasonality in terms of both Hg concentrations (5-7-fold higher in fall than in winter) and isotope compositions. Combining characteristic isotope compositions of potential Hg sources and air mass trajectories, we conclude that underground coal fires were still emitting large amounts of Hg into the atmosphere that have been transported to the adjacent urban area in the prevailing downwind direction. The other local anthropogenic Hg emissions were only evident in the urban atmosphere when the arriving air masses did not pass directly through the coalfield. Our study demonstrates that atmospheric Hg isotope measurement is a useful tool for detecting concealed underground coal fires.
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Poluentes Atmosféricos , Poluentes Ambientais , Incêndios , Mercúrio , Mercúrio/análise , Isótopos de Mercúrio/análise , Carvão Mineral/análise , China , Poluentes Atmosféricos/análise , Monitoramento AmbientalRESUMO
Deep oceans receive mercury (Hg) from upper oceans, sediment diagenesis, and submarine volcanism; meanwhile, sinking particles shuttle Hg to marine sediments. Recent studies showed that Hg in the trench fauna mostly originated from monomethylmercury (MMHg) of the upper marine photosynthetic food webs. Yet, Hg sources in the deep-sea chemosynthetic food webs are still uncertain. Here, we report Hg concentrations and stable isotopic compositions of indigenous biota living at hydrothermal fields of the Indian Ocean Ridge and a cold seep of the South China Sea along with hydrothermal sulfide deposits. We find that Hg is highly enriched in hydrothermal sulfides, which correlated with varying Hg concentrations in inhabited biota. Both the hydrothermal and cold seep biota have small fractions (<10%) of Hg as MMHg and slightly positive Δ199Hg values. These Δ199Hg values are slightly higher than those in near-field sulfides but are 1 order of magnitude lower than the trench counterparts. We suggest that deep-sea chemosynthetic food webs mainly assimilate Hg from ambient seawater/sediments and hydrothermal fluids formed by percolated seawater through magmatic/mantle rocks. The MMHg transfer from photosynthetic to chemosynthetic food webs is likely limited. The contrasting Hg sources between chemosynthetic and trench food webs highlight Hg isotopes as promising tools to trace the deep-sea Hg biogeochemical cycle.
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Mercúrio , Poluentes Químicos da Água , Isótopos de Mercúrio/análise , Cadeia Alimentar , Monitoramento Ambiental , Mercúrio/análise , Isótopos , Oceano Índico , Biota , Poluentes Químicos da Água/análiseRESUMO
By bridging theoretical perspectives from diverse disciplines including public relations, organizational communication, psychology, and management, this study advances a sequential mediation process model that links leaders' motivational communication-specifically, direction-giving, empathetic, and meaning-making language-to employees' organizational engagement during times of crisis. The model incorporates employees' psychological needs satisfaction and their subsequent crisis coping strategies so as to explain the process that underlies the effects of leader communication on employee engagement. We tested the model in a unique yet underexplored crisis context: organizational crises triggered by the global pandemic of COVID-19. The results of an online survey of 490 full-time U.S. employees provide strong support to the model's predictions. Our research extends internal crisis communication scholarship in public relations by addressing what types of leader communication strategies as well as how these strategies contribute to employee engagement in a holistic fashion. It also advances theoretical development of the motivational language theory, self-determination theory, transactional model of stress and coping, and organizational engagement-the four theoretical bases of our study-in the context of organizational crises. Lastly, the study results provide timely practical insights on effective internal crisis communication.
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Haze with high loading of particles may result in significant enrichment of particle-bound Hg (PBM), potentially impacting the atmospheric Hg transformation and transport. However, the dynamics of Hg transformation and the relative environmental effect during severe haze episodes remain unclear. Here, we report Hg isotopic compositions of atmospheric particles (PM2.5, PM10, and TSP) collected during a severe haze episode in Tianjin, China, to investigate the transformation and fate of Hg during haze events. All severe haze samples display significantly higher Δ199Hg (up to 1.50) than global urban PBM, which cannot be explained by primary anthropogenic emissions. The high Δ199Hg is likely caused by photoreduction of PBM promoted by water-soluble organic carbon (WSOC) during the particle accumulation period, as demonstrated by the positive correlations of Δ199Hg with WSOC and relative humidity and confirmed by our laboratory-controlled photoreduction experiment. The results show that, on average, 21% of PBM are likely photoreduced and re-emitted back to the atmosphere as Hg(0), potentially requiring revision of atmospheric Hg budgeting and modeling. This study highlights the release of large portions of PBM back to the gas phase through photoreduction, which needs to be taken into account while evaluating the atmospheric Hg cycle and the relative ecological effects.
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Poluentes Atmosféricos , Mercúrio , Poluentes Atmosféricos/análise , Carbono/análise , China , Monitoramento Ambiental/métodos , Isótopos , Mercúrio/análise , Isótopos de Mercúrio/análise , ÁguaRESUMO
Mercury (Hg) stable isotope analysis has become a powerful tool to identify Hg sources and to understand its biogeochemical processes. However, it is challenging to link the observed Hg isotope fractionation to its global cycling. Here, we integrate source Hg isotope signatures and process-based Hg isotope fractionation into a three-dimensional isotope model based on the GEOS-Chem model platform. Our simulated isotope compositions of total gaseous Hg (TGM) are broadly comparable with available observations across global regions. The isotope compositions of global TGM, potentially distinguishable over different regions, are caused by the atmospheric mixture of anthropogenic, natural, and re-emitted Hg sources, superimposed with competing processes, notably gaseous Hg(0) dry deposition and Hg redox transformations. We find that Hg(0) dry deposition has a great impact on the isotope compositions of global TGM and drives the seasonal variation of δ202Hg in forest-covered regions. The atmospheric photo-reduction of Hg(â ¡) dominates over Hg(0) oxidation in driving the global Δ199Hg (and Δ201Hg) distribution patterns in TGM. We suggest that the magnitude of isotope fractionation associated with atmospheric aqueous-phase Hg(â ¡) reduction is likely close to aquatic Hg(â ¡) reduction. Our model provides a vital tool for coupling the global atmospheric Hg cycle and its isotope fractionation at various scales and advances our understanding of atmospheric Hg transfer and transformation mechanisms.
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Mercúrio , Atmosfera/análise , Fracionamento Químico , Monitoramento Ambiental/métodos , Gases/análise , Isótopos/análise , Mercúrio/análise , Isótopos de Mercúrio/análiseRESUMO
Nature archives record atmospheric mercury (Hg) depositions from directly emitted Hg and re-emitted legacy Hg. Tracing the legacy versus newly deposited Hg is still, however, challenging. Here, we measured Hg isotope compositions in three dated sediment cores at different distances from the Flin Flon smelter, the largest Canadian Hg sources to the atmosphere during the 1930s-2000s. During the smelter's operative period, Hg isotope compositions showed limited variations in the near-field lake (<10 km) sediments but were rather variable in middle- (20-75 km) and far-field lake (â¼800 km) sediments. Only the post-2000 sediments in middle/far-field lakes showed significantly negative Hg isotope shifts, while sediments from the 1970s-1990s had Hg isotope values resembling those of near-field lake post-1930 sediments. We suggest that the smelter's peak Hg emissions during the 1970s-1990s, which coincided with the deployment of a super stack in the mid-1970s, largely increased the long-range dispersion of smelter plumes. For the top post-2000 sediments, the fugitive dust from ore tailings and terrestrial legacy Hg re-emissions dominated Hg deposition in near-field lakes and middle/far-field lakes, respectively. Our study demonstrates that legacy Hg remobilization now exports substantial amounts of Hg to ecosystems, highlighting the need for aggressive remediation measures of Hg-contaminated sites.
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Mercúrio , Poluentes Químicos da Água , Canadá , Ecossistema , Monitoramento Ambiental , Sedimentos Geológicos , Isótopos , Lagos , Mercúrio/análise , Isótopos de Mercúrio , Metais , Poluentes Químicos da Água/análiseRESUMO
Epidemiological studies have shown that maternal hormone exposure is associated with autism spectrum disorders (ASD). The hormone oxytocin (OXT) is a central nervous neuropeptide that plays an important role in social behaviors as well as ASD etiology, although the detailed mechanism remains largely unknown. In this study, we aim to investigate the potential role and contribution of OXT to prenatal progestin exposure-mediated mouse offspring. Our in vitro study in the hypothalamic neurons that isolated from paraventricular nuclei area of mice showed that transient progestin exposure causes persistent epigenetic changes on the OXT promoter, resulting in dissociation of estrogen receptor ß (ERß) and retinoic acid-related orphan receptor α (RORA) from the OXT promoter with subsequent persistent OXT suppression. Our in vivo study showed that prenatal exposure of medroxyprogesterone acetate (MPA) triggers social deficits in mouse offspring; prenatal OXT deficiency in OXT knockdown mouse partly mimics, while postnatal ERß expression or postnatal OXT peptide injection partly ameliorates, prenatal MPA exposure-mediated social deficits, which include impaired social interaction and social abilities. On the other hand, OXT had no effect on prenatal MPA exposure-mediated anxiety-like behaviors. We conclude that prenatal MPA exposure-mediated oxytocin suppression contributes to social deficits in mouse offspring.
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Ocitocina , Progestinas , Animais , Feminino , Camundongos , Neurônios/metabolismo , Ocitocina/metabolismo , Gravidez , Comportamento Social , EsteroidesRESUMO
This study investigated young millennials' risk perception, benefit perception, and purchase intention toward GM foods by testing the effects of source credibility and risk attitude. By comparing two samples collected in the U.S. (N = 207) and China (N = 242), we found that source credibility positively influenced benefit perceptions of GM foods among Chinese millennial consumers. Results also revealed risk attitude significantly influenced both American and Chinese millennial consumers' intention to purchase GM foods. Furthermore, a significant interaction effect between source credibility and risk attitude was found on Chinese millennial consumers' risk perception of GM foods.
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Comportamento do Consumidor , Intenção , Atitude , Alimentos , Humanos , Percepção , Inquéritos e QuestionáriosRESUMO
Severe environmental issues are caused by long-term coal mining activities; however, the process of mercury (Hg) response in mining subsidence area sediments (MSAS) is still unclear, and direct evidence showing the relationship between Hg accumulation mechanism in sediments and mining activities is lacking. In this study, the characteristics of total mercury (THg) content in MSAS were investigated. Moreover, Hg isotopes were obtained to determine the main sources and environmental process of mercury in MSAS, and a MixSIAR mixing model was first used to estimate the potential Hg sources. The THg content ranged from 27.5 to 113.9 ng/g, with a mean of 65.8 ± 29.4 ng/g, exceeding the local soil background value (19.7 ng/g). The Hg in MSAS was affected by clay and organic matter. The Δ199Hg and Δ201Hg in the sediments varied from - 0.05-0.05 (mean: -0.01 ± 0.03) and - 0.07-0.01 (mean: -0.02 ± 0.03), respectively, with the fitting results suggesting that a photochemical reaction occurred in some of the Hg in the sediments prior to deposition. The results of the MixSIAR mixing model revealed that the Hg in MSAS was mainly derived from gangue, soil erosion, coal, fly ash, and feed, and their corresponding percentage contribution was 51.5 ± 9.6%, 23.8 ± 13.1%, 13.9 ± 7.9%, 8.1 ± 5.4%, and 3.1 ± 1.4%, respectively. Hg isotopes can be used to trace the transport and transformation of environmental pollutants, and this may provide an important reference for the assessment and prevention of Hg pollution in typical areas such as coal mining and coal-fired.
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Epidemiological studies have shown that maternal diabetes is associated with autism spectrum disorder development, although the detailed mechanism remains unclear. We have previously found that maternal diabetes induces persistent epigenetic changes and gene suppression in neurons, subsequently triggering autism-like behavior (ALB). In this study, we investigated the potential role and effect of hematopoietic stem cells (HSCs) on maternal diabetes-mediated gastrointestinal (GI) dysfunction and ALB in a mouse model. We show in vitro that transient hyperglycemia induced persistent epigenetic changes and gene suppression of tight junction proteins. In vivo, maternal diabetes-mediated oxidative stress induced gene suppression and inflammation in both peripheral blood mononuclear cells and intestine epithelial cells, subsequently triggering GI dysfunction with increased intestinal permeability and altered microbiota compositions, as well as suppressed gene expression in neurons and subsequent ALB in offspring; HSC transplantation (HSCT) ameliorates this effect by systematically reversing maternal diabetes-mediated oxidative stress. We conclude that HSCT can ameliorate maternal diabetes-mediated GI symptoms and autism-like behavior in mouse offspring.
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Transtorno do Espectro Autista , Transtorno Autístico , Diabetes Gestacional , Gastroenteropatias , Transplante de Células-Tronco Hematopoéticas , Animais , Transtorno Autístico/etiologia , Transtorno Autístico/terapia , Feminino , Gastroenteropatias/etiologia , Gastroenteropatias/terapia , Humanos , Leucócitos Mononucleares/metabolismo , Camundongos , GravidezRESUMO
BACKGROUND: Heterozygous familial hypercholesterolemia (FH) represents the most frequent monogenic disorder with an estimated prevalence of 1:250 in the general population. Diagnosis during childhood enables early initiation of preventive measures, reducing the risk of severe consecutive atherosclerotic manifestations. Nevertheless, population-based screening programs for FH are scarce. METHODS: In the VRONI study, children aged 5-14 years in Bavaria are invited to participate in an FH screening program during regular pediatric visits. The screening is based on low-density lipoprotein cholesterol measurements from capillary blood. If exceeding 130 mg/dl (3.34 mmol/l), i.e. the expected 95th percentile in this age group, subsequent molecular genetic analysis for FH is performed. Children with FH pathogenic variants enter a registry and are treated by specialized pediatricians. Furthermore, qualified training centers offer FH-focused training courses to affected families. For first-degree relatives, reverse cascade screening is recommended to identify and treat affected family members. RESULTS: Implementation of VRONI required intensive prearrangements for addressing ethical, educational, data safety, legal and organizational aspects, which will be outlined in this article. Recruitment started in early 2021, within the first months, more than 380 pediatricians screened over 5200 children. Approximately 50 000 children are expected to be enrolled in the VRONI study until 2024. CONCLUSIONS: VRONI aims to test the feasibility of a population-based screening for FH in children in Bavaria, intending to set the stage for a nationwide FH screening infrastructure. Furthermore, we aim to validate genetic variants of unclear significance, detect novel causative mutations and contribute to polygenic risk indices (DRKS00022140; August 2020).
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Hiperlipoproteinemia Tipo II , Idoso de 80 Anos ou mais , Criança , Diagnóstico Precoce , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Programas de RastreamentoRESUMO
Retinoic acid-related orphan receptor alpha (RORA) suppression is associated with autism spectrum disorder (ASD) development, although the mechanism remains unclear. In this study, we aim to investigate the potential effect and mechanisms of RORA suppression on autism-like behavior (ALB) through maternal diabetes-mediated mouse model. Our in vitro study in human neural progenitor cells shows that transient hyperglycemia induces persistent RORA suppression through oxidative stress-mediated epigenetic modifications and subsequent dissociation of octamer-binding transcription factor 3/4 from the RORA promoter, subsequently suppressing the expression of aromatase and superoxide dismutase 2. The in vivo mouse study shows that prenatal RORA deficiency in neuron-specific RORA null mice mimics maternal diabetes-mediated ALB; postnatal RORA expression in the amygdala ameliorates, while postnatal RORA knockdown mimics, maternal diabetes-mediated ALB in offspring. In addition, RORA mRNA levels in peripheral blood mononuclear cells decrease to 34.2% in ASD patients (n = 121) compared to the typically developing group (n = 118), and the related Receiver Operating Characteristic curve shows good sensitivity and specificity with a calculated 84.1% of Area Under the Curve for ASD diagnosis. We conclude that maternal diabetes contributes to ALB in offspring through suppression of RORA and aromatase, RORA expression in PBMC could be a potential marker for ASD screening.
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Aromatase/genética , Transtorno do Espectro Autista/genética , Diabetes Gestacional/enzimologia , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/antagonistas & inibidores , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Animais , Aromatase/metabolismo , Modelos Animais de Doenças , Feminino , Camundongos , GravidezRESUMO
Familial hypercholesterolemia (FH) is the most frequent monogenic disorder (prevalence 1:250) in the general population. Early diagnosis during childhood enables pre-emptive treatment, thus reducing the risk of severe atherosclerotic manifestations later in life. Nonetheless, FH screening programs are scarce. VRONI offers all children aged 5-14 years in Bavaria a FH screening in the context of regular pediatric visits. LDL-cholesterol (LDL-C) is measured centrally, followed by genetic analysis for FH if exceeding the age-specific 95th percentile (130 mg/dl, 3.34 mmol/l). Children with FH pathogenic variants are treated by specialized pediatricians and offered a FH-focused training course by a qualified training center. Reverse cascade screening is recommended for all first-degree relatives. VRONI aims to prove the feasibility of a population-based FH screening in children and to lay the foundation for a nationwide screening program.
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Despite Australia's high reliance on coal for electricity generation, no study has addressed the extent to which mercury (Hg) deposition has increased since the commissioning of coal-fired power plants. We present stratigraphic data from lake sediments in the Hunter Valley (New South Wales) and Latrobe Valley (Victoria), where a significant proportion of Australia's electricity is generated via coal combustion. Mercury deposition in lake sediments increased in the 1970s with the commissioning of coal-fired power plants, by a factor of 2.9-times in sediments of Lake Glenbawn (Hunter Valley) and 14-times in Traralgon Reservoir (Latrobe Valley). Sediments deposited after the commissioning of power plants have distinct Hg isotope compositions, similar to those of combusted coals. Mercury emission, estimated using an atmospheric model (CALPUFF), was higher in the Latrobe Valley than in the Hunter Valley. This is a result of higher Hg concentrations in lignite coal, lax regulation and older pollution-control technologies adopted by coal-fired power plants in the Latrobe Valley. Near-source deposition of Hg in Australia is significantly higher than North America and Europe, where better emission controls (e.g. wet flue gas desulfurization) have been in effect for decades. The challenge for Australia in years to come will be to ratify the Minamata Convention and develop better regulation policies to reduce Hg emissions.