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1.
Sensors (Basel) ; 24(6)2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38544108

RESUMO

Virtual testing and validation are building blocks in the development of autonomous systems, in particular autonomous driving. Perception sensor models gained more attention to cover the entire tool chain of the sense-plan-act cycle, in a realistic test setup. In the literature or state-of-the-art software tools various kinds of lidar sensor models are available. We present a point cloud lidar sensor model, based on ray tracing, developed for a modular software architecture, which can be used stand-alone. The model is highly parametrizable and designed as a toolbox to simulate different kinds of lidar sensors. It is linked to an infrared material database to incorporate physical sensor effects introduced by the ray-surface interaction. The maximum detectable range depends on the material reflectivity, which can be covered with this approach. The angular dependence and maximum range for different Lambertian target materials are studied. Point clouds from a scene in an urban street environment are compared for different sensor parameters.

2.
Biol Sex Differ ; 15(1): 26, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532495

RESUMO

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key player of lipid metabolism with higher plasma levels in women throughout their life. Statin treatment affects PCSK9 levels also showing evidence of sex-differential effects. It remains unclear whether these differences can be explained by genetics. METHODS: We performed genome-wide association meta-analyses (GWAS) of PCSK9 levels stratified for sex and statin treatment in six independent studies of Europeans (8936 women/11,080 men respectively 14,825 statin-free/5191 statin-treated individuals). Loci associated in one of the strata were tested for statin- and sex-interactions considering all independent signals per locus. Independent variants at the PCSK9 gene locus were then used in a stratified Mendelian Randomization analysis (cis-MR) of PCSK9 effects on low-density lipoprotein cholesterol (LDL-C) levels to detect differences of causal effects between the subgroups. RESULTS: We identified 11 loci associated with PCSK9 in at least one stratified subgroup (p < 1.0 × 10-6), including the PCSK9 gene locus and five other lipid loci: APOB, TM6SF2, FADS1/FADS2, JMJD1C, and HP/HPR. The interaction analysis revealed eight loci with sex- and/or statin-interactions. At the PCSK9 gene locus, there were four independent signals, one with a significant sex-interaction showing stronger effects in men (rs693668). Regarding statin treatment, there were two significant interactions in PCSK9 missense mutations: rs11591147 had stronger effects in statin-free individuals, and rs11583680 had stronger effects in statin-treated individuals. Besides replicating known loci, we detected two novel genome-wide significant associations: one for statin-treated individuals at 6q11.1 (within KHDRBS2) and one for males at 12q24.22 (near KSR2/NOS1), both with significant interactions. In the MR of PCSK9 on LDL-C, we observed significant causal estimates within all subgroups, but significantly stronger causal effects in statin-free subjects compared to statin-treated individuals. CONCLUSIONS: We performed the first double-stratified GWAS of PCSK9 levels and identified multiple biologically plausible loci with genetic interaction effects. Our results indicate that the observed sexual dimorphism of PCSK9 and its statin-related interactions have a genetic basis. Significant differences in the causal relationship between PCSK9 and LDL-C suggest sex-specific dosages of PCSK9 inhibitors.


The protein "proprotein convertase subtilisin/kexin type 9" (PCSK9) regulates the levels of low-density lipoprotein cholesterol (LDL-C) in blood, and thus, contributes to the risk of cardio-vascular diseases. Women tend to have higher PCSK9 plasma levels throughout their life, although the difference is smaller in patients under LDL-C lowering medication (e.g., statins). We investigated the interplay of genetics, statin-treatment and sex, using combined data from six European studies. We detected 11 genetic regions associated with PCSK9 levels, of which one was specific for women (at SLCO1B3, a statin-transporter gene), and three were specific for men (e.g., ALOX5, encoding a protein linked to chronic inflammatory diseases such as atherosclerosis). We also tested if statin use changed the genetic effect and found five genes only associated with PCSK9 levels in untreated participants. Variants in the gene encoding PCSK9 were most strongly associated and had heterogeneous effects in dependence on statin treatment and sex: On one hand, there were genetic variants with stronger effects in men than women. Those variants are also linked to sex-differential gene expression of PCSK9. On the other hand, there were also variants with treatment-depending effects, linked to protein structure and functionality of PCSK9. This indicates that the observed sexual and treatment-related effects on PCSK9 levels have a genetic basis. In addition, we compared the causal effects of PCSK9 on LDL-C levels between men and women and found a different response to statin treatment. This highlights the need for sex-sensitive dosages of lipid-lowering medication.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Masculino , Humanos , Feminino , Pró-Proteína Convertase 9/genética , Pró-Proteína Convertase 9/metabolismo , Estudo de Associação Genômica Ampla , LDL-Colesterol/genética , Oxirredutases N-Desmetilantes , Histona Desmetilases com o Domínio Jumonji
3.
Sci Total Environ ; 921: 170750, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38336073

RESUMO

Anthropogenic disturbances, including extraction of natural resources and development of alternative energy, are reducing and fragmenting habitat for wildlife across the globe. Effects of those disturbances have been explored by studying populations that migrate through oil and gas fields or alternative energy facilities. Extraction of minerals, including precious metals and lithium, is increasing rapidly in remote areas, which results in dramatically altered landscapes in areas of resident populations of wildlife. Our goal was to examine how a resident population of American pronghorn (Antilocapra americana) in the Great Basin ecosystem selected resources near a large-scale disturbance year around. We investigated how individuals selected resources around a large, open-pit gold mine. We classified levels of disturbance associated with the mine, and used a random forest model to select ecological covariates associated with habitat selection by pronghorn. We used resource selection functions to examine how disturbances affected habitat selection by pronghorn both annually and seasonally. Pronghorn strongly avoided areas of high disturbance, which included open pits, heap leach fields, rock disposal areas, and a tram. Pronghorn selected areas near roads, although selection was strongest about 2 km away. We observed relatively broad variation among individuals in selection of resources, and how they responded to the mine. The Great Basin is a mineral-rich area that continues to be exploited for natural resources, especially minerals. Sagebrush-dependent species, including pronghorn, that rely on this critical habitat were directly affected by that transformation of the landscape, which is likely to increase with expansion of the mine. As extraction of minerals from remote landscapes around the world continues to fragment habitats for wildlife, increasing our understanding of impacts of those changes on behaviors of wildlife before populations decline, may assist in the mitigation and minimization of negative impacts on mineral-rich landscapes and on wildlife populations.


Assuntos
Ecossistema , Ouro , Humanos , Animais , Conservação dos Recursos Naturais/métodos , Animais Selvagens , Ruminantes , Minerais
4.
Blood ; 143(18): 1845-1855, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38320121

RESUMO

ABSTRACT: Coagulation factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are critical to coagulation and platelet aggregation. We leveraged whole-genome sequence data from the Trans-Omics for Precision Medicine (TOPMed) program along with TOPMed-based imputation of genotypes in additional samples to identify genetic associations with circulating FVIII and VWF levels in a single-variant meta-analysis, including up to 45 289 participants. Gene-based aggregate tests were implemented in TOPMed. We identified 3 candidate causal genes and tested their functional effect on FVIII release from human liver endothelial cells (HLECs) and VWF release from human umbilical vein endothelial cells. Mendelian randomization was also performed to provide evidence for causal associations of FVIII and VWF with thrombotic outcomes. We identified associations (P < 5 × 10-9) at 7 new loci for FVIII (ST3GAL4, CLEC4M, B3GNT2, ASGR1, F12, KNG1, and TREM1/NCR2) and 1 for VWF (B3GNT2). VWF, ABO, and STAB2 were associated with FVIII and VWF in gene-based analyses. Multiphenotype analysis of FVIII and VWF identified another 3 new loci, including PDIA3. Silencing of B3GNT2 and the previously reported CD36 gene decreased release of FVIII by HLECs, whereas silencing of B3GNT2, CD36, and PDIA3 decreased release of VWF by HVECs. Mendelian randomization supports causal association of higher FVIII and VWF with increased risk of thrombotic outcomes. Seven new loci were identified for FVIII and 1 for VWF, with evidence supporting causal associations of FVIII and VWF with thrombotic outcomes. B3GNT2, CD36, and PDIA3 modulate the release of FVIII and/or VWF in vitro.


Assuntos
Moléculas de Adesão Celular , Fator VIII , Cininogênios , Lectinas Tipo C , Receptores de Superfície Celular , Fator de von Willebrand , Humanos , Fator de von Willebrand/genética , Fator de von Willebrand/metabolismo , Fator VIII/genética , Fator VIII/metabolismo , Polimorfismo de Nucleotídeo Único , Células Endoteliais da Veia Umbilical Humana/metabolismo , Análise da Randomização Mendeliana , Estudo de Associação Genômica Ampla , Trombose/genética , Trombose/sangue , Estudos de Associação Genética , Masculino , Células Endoteliais/metabolismo , Feminino
5.
Nat Commun ; 15(1): 264, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38238311

RESUMO

Alzheimer's disease (AD) is characterized by progressive neurodegeneration, but the specific events that cause cell death remain poorly understood. Death Induced by Survival gene Elimination (DISE) is a cell death mechanism mediated by short (s) RNAs acting through the RNA-induced silencing complex (RISC). DISE is thus a form of RNA interference, in which G-rich 6mer seed sequences in the sRNAs (position 2-7) target hundreds of C-rich 6mer seed matches in genes essential for cell survival, resulting in the activation of cell death pathways. Here, using Argonaute precipitation and RNAseq (Ago-RP-Seq), we analyze RISC-bound sRNAs to quantify 6mer seed toxicity in several model systems. In mouse AD models and aging brain, in induced pluripotent stem cell-derived neurons from AD patients, and in cells exposed to Aß42 oligomers, RISC-bound sRNAs show a shift to more toxic 6mer seeds compared to controls. In contrast, in brains of "SuperAgers", humans over age 80 who have superior memory performance, RISC-bound sRNAs are shifted to more nontoxic 6mer seeds. Cells depleted of nontoxic sRNAs are sensitized to Aß42-induced cell death, and reintroducing nontoxic RNAs is protective. Altogether, the correlation between DISE and Aß42 toxicity suggests that increasing the levels of nontoxic miRNAs in the brain or blocking the activity of toxic RISC-bound sRNAs could ameliorate neurodegeneration.


Assuntos
Doença de Alzheimer , MicroRNAs , Camundongos , Animais , Humanos , Idoso de 80 Anos ou mais , Doença de Alzheimer/genética , MicroRNAs/genética , Complexo de Inativação Induzido por RNA/genética , Interferência de RNA , Envelhecimento/genética , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/toxicidade
6.
bioRxiv ; 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38260662

RESUMO

The red nucleus is a large brainstem structure that coordinates limb movement for locomotion in quadrupedal animals (Basile et al., 2021). The humans red nucleus has a different pattern of anatomical connectivity compared to quadrupeds, suggesting a unique purpose (Hatschek, 1907). Previously the function of the human red nucleus remained unclear at least partly due to methodological limitations with brainstem functional neuroimaging (Sclocco et al., 2018). Here, we used our most advanced resting-state functional connectivity (RSFC) based precision functional mapping (PFM) in highly sampled individuals (n = 5) and large group-averaged datasets (combined N ~ 45,000), to precisely examine red nucleus functional connectivity. Notably, red nucleus functional connectivity to motor-effector networks (somatomotor hand, foot, and mouth) was minimal. Instead, red nucleus functional connectivity along the central sulcus was specific to regions of the recently discovered somato-cognitive action network (SCAN; (Gordon et al., 2023)). Outside of primary motor cortex, red nucleus connectivity was strongest to the cingulo-opercular (CON) and salience networks, involved in action/cognitive control (Dosenbach et al., 2007; Newbold et al., 2021) and reward/motivated behavior (Seeley, 2019), respectively. Functional connectivity to these two networks was organized into discrete dorsal-medial and ventral-lateral zones. Red nucleus functional connectivity to the thalamus recapitulated known structural connectivity of the dento-rubral thalamic tract (DRTT) and could prove clinically useful in functionally targeting the ventral intermediate (VIM) nucleus. In total, our results indicate that far from being a 'motor' structure, the red nucleus is better understood as a brainstem nucleus for implementing goal-directed behavior, integrating behavioral valence and action plans.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38196142

RESUMO

AIMS: To investigate the prevalence of familial hypercholesterolaemia (FH) and compare the performance of clinical criteria and genetic testing in patients undergoing coronary angiography. METHODS: The prevalence of FH was determined with the Dutch Lipid Clinical Network (DLCN), US-MEDPED, Simon Broome (SB) criteria, the 'Familial Hypercholesterolaemia Case Ascertainment Tool' (FAMCAT), and a clinical algorithm. Genetic screening was conducted with a custom array from Affymetrix (CARRENAL array) harboring 944 FH mutations. RESULTS: The study cohort consisted of 3267 patients (78.6% with coronary artery disease [CAD]). FH was diagnosed in 2.8%, 2.2%, 3.9%, and 7.9% using the DLCN, US-MEDPED, SB criteria, and the FAMCAT. The clinical algorithm identified the same patients as the SB criteria. Pathogenic FH mutations were found in 1.2% (1.2% in patients with CAD, 1.0% in patients without CAD). FH was more frequently diagnosed in younger patients. With genetic testing as reference, the clinical criteria achieved areas under the ROC curve (AUCs) in the range of 0.56-0.68. Using only LDL-C corrected for statin intake, an AUC of 0.68 was achieved. CONCLUSION: FH is up to fourfold more prevalent in patients undergoing coronary angiography than in contemporary cohorts representing the general population. Different clinical criteria yield substantially different diagnosis rates, overestimating the prevalence of FH compared to genetic testing. LDL-C testing alone may be sufficient to raise the suspicion of FH, which then needs to be corroborated by genetic testing.

9.
MethodsX ; 12: 102484, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38292315

RESUMO

This study aims to present a combination of methods and propose robust theoretical and conceptual frameworks for solving socio-environmental issues. This proposal included the Problem, Intervention, Context, and Outcome (PICO) framework and Protocol and Reporting result with Search, Appraisal, Synthesis, and Analysis framework, and develop (PSALSAR) method through SODIP steps: (i) Systematic review and meta-analysis defining the study from guiding questions; (ii) Open-source related to software and data; (iii) Data visualization and design information; (iv) Identification of gaps, challenges and trends through automation and lexicometric analysis; and (v) Proposal of theoretical and conceptual frameworks. This proposal defines the steps as support to combine and systematize information necessary to facilitate the production of this type of document using open-access software in the visualization and design of information. All these steps are replicable and essential to propose a conceptual and theoretical framework to contribute to the construction of knowledge in socio-environmental research and to propose solutions by filling in the gaps. In summary, this combination of methods shows:•The use of SODIP steps provides robustness and efficiency in carrying out review studies, facilitating the way to propose theoretical or conceptual frameworks.•Choosing to use open-source tools is essential for better evaluation and visualization of qualitative and quantitative data in review studies.•The combination of methods and data in the systematic review (scientific, political documents. and databases) supports the proposal of robust theoretical and conceptual frameworks.

10.
Am J Emerg Med ; 76: 193-198, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38091903

RESUMO

INTRODUCTION: Restraint use in the emergency department (ED) can pose significant risks to patients and health care workers. We evaluate the effectiveness of Code De-escalation- a standardized, team-based approach for management and assessment of threatening behaviors- in reducing physical restraint use and workplace violence in a community ED. METHODS: A retrospective observational study of a pathway on physical restraint use among patients placed on an involuntary psychiatric hold in a community ED. This pathway includes a built-in step for the team members to systematically assess perceptions of threats from the patient behavior and threats perceived by the patient. Our primary outcome was the change in the rate of physical restraint use among patients on an involuntary psychiatric hold. Our secondary outcome was the change in the rate of workplace violence events involving all ED encounters. We evaluated our outcomes by comparing all encounters in a ten-month period before and after implementation, and compared our results to rates at neighboring community hospitals within the same hospital network. RESULTS: Pre intervention there were 434 ED encounters involving a psychiatric hold, post-intervention there were 535. We observed a significant decrease in physical restraint use, from 7.4% to 3.7% (ARR 0.028 [95% CI 0.002-0.055], p < 0.05). This was not seen at the control sites. CONCLUSIONS: A standardized de-escalation algorithm can be effective in helping ED's decrease their use of physical restraints in management of psychiatric patients experiencing agitation.


Assuntos
Restrição Física , Violência no Trabalho , Humanos , Restrição Física/métodos , Hospitais Comunitários , Serviço Hospitalar de Emergência , Agressão
11.
Mar Pollut Bull ; 198: 115862, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38041886

RESUMO

This study investigates the concentration of metals in the different developmental phases of the gonads of Ucides cordatus from mangrove areas of Vila do Bacuriteua on the Bragança Peninsula, Caeté-Taperaçu Marine Extractive Reserve, state of Pará, on the Brazilian Amazon coast. Elemental analysis was determined by inductively coupled plasma optical emission spectrometry (ECP-OES). Metal concentration in males ranged from Cd = 0.04 to Cu = 2.27 mg kg-1 ww in the Developing and Developed gonadal stages, respectively. In females it was from Cd = 0.11 to Cu = 8.43 mg kg-1 ww only in the Developed stage). The elements Cr and Pb, for both sexes, presented concentrations above the limits allowed by the Brazilian regulatory body and only Pb by the international agencies, revealing a higher degree of contamination of these metals in the gonads of the mangrove crabs. Increasing mangrove crab consumption amplifies the risks of metal contamination among the human population and may cause public health problems.


Assuntos
Braquiúros , Metais Pesados , Poluentes Químicos da Água , Masculino , Humanos , Animais , Feminino , Braquiúros/química , Cádmio/análise , Chumbo/análise , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análise , Biomarcadores/análise , Metais Pesados/análise
12.
bioRxiv ; 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-37987000

RESUMO

Motor adaptation in cortico-striato-thalamo-cortical loops has been studied mainly in animals using invasive electrophysiology. Here, we leverage functional neuroimaging in humans to study motor circuit plasticity in the human subcortex. We employed an experimental paradigm that combined two weeks of upper-extremity immobilization with daily resting-state and motor task fMRI before, during, and after the casting period. We previously showed that limb disuse leads to decreased functional connectivity (FC) of the contralateral somatomotor cortex (SM1) with the ipsilateral somatomotor cortex, increased FC with the cingulo-opercular network (CON) as well as the emergence of high amplitude, fMRI signal pulses localized in the contralateral SM1, supplementary motor area and the cerebellum. From our prior observations, it remains unclear whether the disuse plasticity affects the thalamus and striatum. We extended our analysis to include these subcortical regions and found that both exhibit strengthened cortical FC and spontaneous fMRI signal pulses induced by limb disuse. The dorsal posterior putamen and the central thalamus, mainly CM, VLP and VIM nuclei, showed disuse pulses and FC changes that lined up with fmri task activations from the Human connectome project motor system localizer, acquired before casting for each participant. Our findings provide a novel understanding of the role of the cortico-striato-thalamo-cortical loops in human motor plasticity and a potential link with the physiology of sleep regulation. Additionally, similarities with FC observation from Parkinson Disease (PD) questions a pathophysiological link with limb disuse.

13.
Lancet Diabetes Endocrinol ; 12(2): 119-131, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38142707

RESUMO

BACKGROUND: Heterogeneity in type 2 diabetes can be represented by a tree-like graph structure by use of reversed graph-embedded dimensionality reduction. We aimed to examine whether this approach can be used to stratify key pathophysiological components and diabetes-related complications during longitudinal follow-up of individuals with recent-onset type 2 diabetes. METHODS: For this cohort analysis, 927 participants aged 18-69 years from the German Diabetes Study (GDS) with recent-onset type 2 diabetes were mapped onto a previously developed two-dimensional tree based on nine simple clinical and laboratory variables, residualised for age and sex. Insulin sensitivity was assessed by a hyperinsulinaemic-euglycaemic clamp, insulin secretion was assessed by intravenous glucose tolerance test, hepatic lipid content was assessed by 1 H magnetic resonance spectroscopy, serum interleukin (IL)-6 and IL-18 were assessed by ELISA, and peripheral and autonomic neuropathy were assessed by functional and clinical measures. Participants were followed up for up to 16 years. We also investigated heart failure and all-cause mortality in 794 individuals with type 2 diabetes undergoing invasive coronary diagnostics from the Ludwigshafen Risk and Cardiovascular Health (LURIC) cohort. FINDINGS: There were gradients of clamp-measured insulin sensitivity (both dimensions: p<0·0001) and insulin secretion (pdim1<0·0001, pdim2=0·00097) across the tree. Individuals in the region with the lowest insulin sensitivity had the highest hepatic lipid content (n=205, pdim1<0·0001, pdim2=0·037), pro-inflammatory biomarkers (IL-6: n=348, pdim1<0·0001, pdim2=0·013; IL-18: n=350, pdim1<0·0001, pdim2=0·38), and elevated cardiovascular risk (nevents=143, pdim1=0·14, pdim2<0·00081), whereas individuals positioned in the branch with the lowest insulin secretion were more prone to require insulin therapy (nevents=85, pdim1=0·032, pdim2=0·12) and had the highest risk of diabetic sensorimotor polyneuropathy (nevents=184, pdim1=0·012, pdim2=0·044) and cardiac autonomic neuropathy (nevents=118, pdim1=0·0094, pdim2=0·06). In the LURIC cohort, all-cause mortality was highest in the tree branch showing insulin resistance (nevents=488, pdim1=0·12, pdim2=0·0032). Significant gradients differentiated individuals having heart failure with preserved ejection fraction from those who had heart failure with reduced ejection fraction. INTERPRETATION: These data define the pathophysiological underpinnings of the tree structure, which has the potential to stratify diabetes-related complications on the basis of routinely available variables and thereby expand the toolbox of precision diabetes diagnosis. FUNDING: German Diabetes Center, German Federal Ministry of Health, Ministry of Culture and Science of the state of North Rhine-Westphalia, German Federal Ministry of Education and Research, German Diabetes Association, German Center for Diabetes Research, European Community, German Research Foundation, and Schmutzler Stiftung.


Assuntos
Complicações do Diabetes , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Resistência à Insulina , Humanos , Interleucina-18 , Estudos Prospectivos , Insulina/uso terapêutico , Lipídeos
14.
Artigo em Inglês | MEDLINE | ID: mdl-38083139

RESUMO

Lower extremity amputation and requirement of peripheral artery revascularization are common outcomes of undiagnosed peripheral artery disease patients. In the current work, prediction models for the need of amputation or peripheral revascularization focused on hypertensive patients within seven years follow up are employed. We applied machine learning (ML) models using classifiers such as Extreme Gradient Boost (XGBoost), Random Forest (RF) and Adaptive Boost (AdaBoost), that will allow clinicians to identify the patients at risk of these two endpoints using simple clinical data. We used the non-interventional cohort of the getABI study in the primary care setting, selecting 4,191 hypertensive patients out of 6,474 patients with age over 65 years old and followed up for vascular events or death up to 7 years. During this follow up period, 150 patients underwent either amputation or peripheral revascularization or both. Accuracy, Specificity, Sensitivity and Area under the receiver operating characteristic curve (AUC) were estimated for each machine learning model. The results demonstrate Random Forest as the most accurate model for the prediction of the composite endpoint in hypertensive patients within 7 years follow-up, achieving 73.27 % accuracy.Clinical Relevance-This study assists clinicians to better predict and treat these serious outcomes, amputation and peripheral revascularization in hypertensive patients.


Assuntos
Artérias , Procedimentos Cirúrgicos Vasculares , Humanos , Idoso , Seguimentos , Amputação Cirúrgica , Aprendizado de Máquina
15.
Chem Soc Rev ; 52(23): 8295-8318, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-37910139

RESUMO

Imaging techniques permit the study of the molecular interactions that underlie health and disease. Each imaging technique collects unique chemical information about the cellular environment. Multimodal imaging, using a single probe that can be detected by multiple imaging modalities, can maximise the information extracted from a single cellular sample by combining the results of different imaging techniques. Of particular interest in biological imaging is the combination of the specificity and sensitivity of optical fluorescence microscopy (OFM) with the quantitative and element-specific nature of X-ray fluorescence microscopy (XFM). Together, these techniques give a greater understanding of how native elements or therapeutics affect the cellular environment. This review focuses on recent studies where both techniques were used in conjunction to study cellular systems, demonstrating the breadth of biological models to which this combination of techniques can be applied and the potential for these techniques to unlock untapped knowledge of disease states.


Assuntos
Microscopia , Imagem Óptica , Raios X
16.
Kidney Blood Press Res ; 48(1): 678-687, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37806305

RESUMO

INTRODUCTION: Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) are risk factors for cardiovascular mortality (CVM). Pulse pressure (PP) is an easily available parameter of vascular stiffness, but its impact on CVM in chronic dialysis patients with diabetes is unclear. METHODS: Therefore, we have examined the predictive value of baseline, predialytic PP, SBP, DBP, and MAP in the German Diabetes and Dialysis (4D) study, a prospective, randomized, double-blind trial enrolling 1,255 patients with type 2 diabetes on hemodialysis in 178 German dialysis centers. RESULTS: Mean age was 66.3 years, mean blood pressure 146/76 mm Hg, mean time suffering from diabetes 18.1 years, and mean time on maintenance dialysis 8.3 months. Considered as continuous variables, PP, MAP, SBP, and DBP could not provide a significant mortality prediction for either cardiovascular or all-cause mortality. After dividing the cohort into corresponding tertiles, we also did not detect any significant mortality prediction for PP, SBP, DBP, or MAP, both for all-cause mortality and CVM after adjusting for age and sex. Nevertheless, when comparing the HR plots of the corresponding blood pressure parameters, a pronounced U-curve was seen for PP for both all-cause mortality and CVM, with the trough range being 70-80 mm Hg. DISCUSSION: In patients with end-stage renal disease and long-lasting diabetes mellitus predialytic blood pressure parameters at study entry are not predictive for mortality, presumably because there is a very high rate of competing mortality risk factors, resulting in overall very high rates of all-cause and CVM that may no longer be significantly modulated by blood pressure control.


Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Humanos , Idoso , Pressão Sanguínea/fisiologia , Diabetes Mellitus Tipo 2/complicações , Estudos Prospectivos , Diálise Renal , Fatores de Risco
17.
JAMA Netw Open ; 6(10): e2337557, 2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37824142

RESUMO

Importance: Emergency department (ED) triage substantially affects how long patients wait for care but triage scoring relies on few objective criteria. Prior studies suggest that Black and Hispanic patients receive unequal triage scores, paralleled by disparities in the depth of physician evaluations. Objectives: To examine whether racial disparities in triage scores and physician evaluations are present across a multicenter network of academic and community hospitals and evaluate whether patients who do not speak English face similar disparities. Design, Setting, and Participants: This was a cross-sectional, multicenter study examining adults presenting between February 28, 2019, and January 1, 2023, across the Mass General Brigham Integrated Health Care System, encompassing 7 EDs: 2 urban academic hospitals and 5 community hospitals. Analysis included all patients presenting with 1 of 5 common chief symptoms. Exposures: Emergency department nurse-led triage and physician evaluation. Main Outcomes and Measures: Average Triage Emergency Severity Index [ESI] score and average visit work relative value units [wRVUs] were compared across symptoms and between individual minority racial and ethnic groups and White patients. Results: There were 249 829 visits (149 861 female [60%], American Indian or Alaska Native 0.2%, Asian 3.3%, Black 11.8%, Hispanic 18.8%, Native Hawaiian or Other Pacific Islander <0.1%, White 60.8%, and patients identifying as Other race or ethnicity 5.1%). Median age was 48 (IQR, 29-66) years. White patients had more acute ESI scores than Hispanic or Other patients across all symptoms (eg, chest pain: Hispanic, 2.68 [95% CI, 2.67-2.69]; White, 2.55 [95% CI, 2.55-2.56]; Other, 2.66 [95% CI, 2.64-2.68]; P < .001) and Black patients across most symptoms (nausea/vomiting: Black, 2.97 [95% CI, 2.96-2.99]; White: 2.90 [95% CI, 2.89-2.91]; P < .001). These differences were reversed for wRVUs (chest pain: Black, 4.32 [95% CI, 4.25-4.39]; Hispanic, 4.13 [95% CI, 4.08-4.18]; White 3.55 [95% CI, 3.52-3.58]; Other 3.96 [95% CI, 3.84-4.08]; P < .001). Similar patterns were seen for patients whose primary language was not English. Conclusions and Relevance: In this cross-sectional study, patients who identified as Black, Hispanic, and Other race and ethnicity were assigned less acute ESI scores than their White peers despite having received more involved physician workups, suggesting some degree of mistriage. Clinical decision support systems might reduce these disparities but would require careful calibration to avoid replicating bias.


Assuntos
Etnicidade , Triagem , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Serviço Hospitalar de Emergência , Dor no Peito
18.
Sci Adv ; 9(41): eadi0186, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37824617

RESUMO

Antarctic ice shelves moderate the contribution of the Antarctic Ice Sheet to global sea level rise; however, ice shelf health remains poorly constrained. Here, we present the annual mass budget of all Antarctic ice shelves from 1997 to 2021. Out of 162 ice shelves, 71 lost mass, 29 gained mass, and 62 did not change mass significantly. Of the shelves that lost mass, 68 had statistically significant negative mass trends, 48 lost more than 30% of their initial mass, and basal melting was the dominant contributor to that mass loss at a majority (68%). At many ice shelves, mass losses due to basal melting or iceberg calving were significantly positively correlated with grounding line discharge anomalies; however, the strength and form of this relationship varied substantially between ice shelves. Our results illustrate the utility of partitioning high-resolution ice shelf mass balance observations into its components to quantify the contributors to ice shelf mass change and the response of grounded ice.

20.
Mol Ther Nucleic Acids ; 33: 773, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37655044
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