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Background and Aims: Gallstone disease (GSD) associates with significant morbidity and mortality. Decreased secretion of bile acids has been suggested as a driving factor for GSD. Recently, we linked the protein phosphatase 1 regulatory subunit 3 beta (PPP1R3B) rs4240624 genotype to decreased bile acid levels in bile. In this study, we investigated whether these individuals had an increased risk for GSD as well as the differences in the lipid composition of the gallbladder bile of these individuals compared to controls and patients with GSD. Methods: Bile acids, cholesterol, and phospholipid levels in gallbladder bile samples were enzymatically measured in 46 patients (34 female, age 45.7 ± 9.8 years, BMI 41.3 ± 4.4 kg/m2) who underwent elective laparoscopic Roux-en-Y gastric bypass. The lipidome of gallbladder bile was analyzed using high-performance liquid chromatography-mass spectrometry. Gallstone status was evaluated using abdominal ultrasonography before the surgery. Results: The G allele of PPP1R3B rs4240624 was significantly associated with GSD in patients with obesity. We validated this association in the UK Biobank. Bile lipidomics demonstrated that 13 of the 17 minor lipid classes measured were higher in individuals with the G allele. The concentrations of bile acids, cholesterol, and phospholipids, as well as the cholesterol saturation index, were lower in patients with GSD than in those without gallstones. GSD had an effect similar to that of PPP1R3B genotype on minor lipids. Conclusion: The PPP1R3B rs4240624 genotype is associated with gallstones and with changes in gallbladder bile similar to those observed in patients with gallstones, suggesting that the PPP1R3B genotype contributes to the risk of gallstones by altering the bile lipidome.
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BACKGROUND: Abdominal obesity increases the risk for non-alcoholic fatty liver disease (NAFLD), now known as metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: To elucidate the directional cell-type level biological mechanisms underlying the association between abdominal obesity and MASLD, we integrated adipose and liver single nucleus RNA-sequencing and bulk cis-expression quantitative trait locus (eQTL) data with the UK Biobank genome-wide association study (GWAS) data using colocalization. Then we used colocalized cis-eQTL variants as instrumental variables in Mendelian randomization (MR) analyses, followed by functional validation experiments on the target genes of the cis-eQTL variants. FINDINGS: We identified 17 colocalized abdominal obesity GWAS variants, regulating 17 adipose cell-type marker genes. Incorporating these 17 variants into MR discovers a putative tissue-of-origin, cell-type-aware causal effect of abdominal obesity on MASLD consistently with multiple MR methods without significant evidence for pleiotropy or heterogeneity. Single cell data confirm the adipocyte-enriched mean expression of the 17 genes. Our cellular experiments across human adipogenesis identify risk variant -specific epigenetic and transcriptional mechanisms. Knocking down two of the 17 genes, PPP2R5A and SH3PXD2B, shows a marked decrease in adipocyte lipidation and significantly alters adipocyte function and adipogenesis regulator genes, including DGAT2, LPL, ADIPOQ, PPARG, and SREBF1. Furthermore, the 17 genes capture a characteristic MASLD expression signature in subcutaneous adipose tissue. INTERPRETATION: Overall, we discover a significant cell-type level effect of abdominal obesity on MASLD and trace its biological effect to adipogenesis. FUNDING: NIH grants R01HG010505, R01DK132775, and R01HL170604; the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (Grant No. 802825), Academy of Finland (Grants Nos. 333021), the Finnish Foundation for Cardiovascular Research the Sigrid Jusélius Foundation and the Jane and Aatos Erkko Foundation; American Association for the Study of Liver Diseases (AASLD) Advanced Transplant Hepatology award and NIH/NIDDK (P30DK41301) Pilot and Feasibility award; NIH/NIEHS F32 award (F32ES034668); Finnish Diabetes Research Foundation, Kuopio University Hospital Project grant (EVO/VTR grants 2005-2021), the Academy of Finland grant (Contract no. 138006); Academy of Finland (Grant Nos 335443, 314383, 272376 and 266286), Sigrid Jusélius Foundation, Finnish Medical Foundation, Finnish Diabetes Research Foundation, Novo Nordisk Foundation (#NNF20OC0060547, NNF17OC0027232, NNF10OC1013354) and Government Research Funds to Helsinki University Hospital; Orion Research Foundation, Maud Kuistila Foundation, Finish Medical Foundation, and University of Helsinki.
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Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Obesidade Abdominal , Locos de Características Quantitativas , Humanos , Obesidade Abdominal/genética , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Polimorfismo de Nucleotídeo Único , Análise de Sequência de RNA , Proteína Fosfatase 2/genética , Proteína Fosfatase 2/metabolismo , Núcleo Celular/metabolismo , Núcleo Celular/genética , Adipogenia/genética , Análise de Célula Única , Regulação da Expressão GênicaRESUMO
BACKGROUND: Obesity is a worldwide epidemic characterized by adipose tissue (AT) inflammation. AT is also a source of extracellular vesicles (EVs) that have recently been implicated in disorders related to metabolic syndrome. However, our understanding of mechanistic aspect of obesity's impact on EV secretion from human AT remains limited. METHODS: We investigated EVs from human Simpson Golabi Behmel Syndrome (SGBS) adipocytes, and from AT as well as plasma of subjects undergoing bariatric surgery. SGBS cells were treated with TNFα, palmitic acid, and eicosapentaenoic acid. Various analyses, including nanoparticle tracking analysis, electron microscopy, high-resolution confocal microscopy, and gas chromatography-mass spectrometry, were utilized to study EVs. Plasma EVs were analyzed with imaging flow cytometry. RESULTS: EVs from mature SGBS cells differed significantly in size and quantity compared to preadipocytes, disagreeing with previous findings in mouse adipocytes and indicating that adipogenesis promotes EV secretion in human adipocytes. Inflammatory stimuli also induced EV secretion, and altered EV fatty acid (FA) profiles more than those of cells, suggesting the role of EVs as rapid responders to metabolic shifts. Visceral AT (VAT) exhibited higher EV secretion compared to subcutaneous AT (SAT), with VAT EV counts positively correlating with plasma triacylglycerol (TAG) levels. Notably, the plasma EVs of subjects with obesity contained a higher number of adiponectin-positive EVs than those of lean subjects, further demonstrating higher AT EV secretion in obesity. Moreover, plasma EV counts of people with obesity positively correlated with body mass index and TNF expression in SAT, connecting increased EV secretion with AT expansion and inflammation. Finally, EVs from SGBS adipocytes and AT contained TAGs, and EV secretion increased despite signs of less active lipolytic pathways, indicating that AT EVs could be involved in the mobilization of excess lipids into circulation. CONCLUSIONS: We are the first to provide detailed FA profiles of human AT EVs. We report that AT EV secretion increases in human obesity, implicating their role in TAG transport and association with adverse metabolic parameters, thereby emphasizing their role in metabolic disorders. These findings promote our understanding of the roles that EVs play in human AT biology and metabolic disorders.
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Adipócitos , Tecido Adiposo , Vesículas Extracelulares , Inflamação , Obesidade , Humanos , Vesículas Extracelulares/metabolismo , Obesidade/metabolismo , Obesidade/patologia , Adipócitos/metabolismo , Inflamação/patologia , Inflamação/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Metabolismo dos Lipídeos , Feminino , Masculino , Adulto , Ácidos Graxos/metabolismoRESUMO
OBJECTIVE: The objective of this study is to explore and enhance the diagnostic process of unipolar and bipolar disorders. The primary focus is on leveraging automated processes to improve the accuracy and accessibility of diagnosis. The study aims to introduce an audio corpus collected from patients diagnosed with these disorders, annotated using the Clinical Global Impressions Scale (CGI) by psychiatrists. METHODS AND PROCEDURES: Traditional diagnostic methods rely on the clinician's expertise and consideration of co-existing mental disorders. However, this study proposes the implementation of automated processes in the diagnosis, providing quantitative measures and enabling prolonged observation of patients. The paper introduces a speech signal pipeline for CGI state classification, with a specific focus on selecting the most discriminative features. Acoustic features such as prosodies, MFCC, and LPC coefficients are examined in the study. The classification process utilizes common machine learning methods. RESULTS: The results of the study indicate promising outcomes for the automated diagnosis of bipolar and unipolar disorders using the proposed speech signal pipeline. The audio corpus annotated with CGI by psychiatrists achieved a classification accuracy of 95% for the two-class classification. For the four- and seven-class classifications, the results were 77.3% and 73%, respectively, demonstrating the potential of the developed method in distinguishing different states of the disorders.
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Transtorno Bipolar , Humanos , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/fisiopatologia , Feminino , Masculino , Fala/fisiologia , Adulto , Aprendizado de Máquina , Processamento de Sinais Assistido por Computador , Pessoa de Meia-Idade , Diagnóstico DiferencialRESUMO
Recent studies demonstrate that liver secretory proteins, also known as hepatokines, regulate normal development, obesity, and simple steatosis to non-alcoholic steatohepatitis (NASH) progression. Using a panel of â¼100 diverse inbred strains of mice and a cohort of bariatric surgery patients, we found that one such hepatokine, inter-trypsin inhibitor heavy chain 3 (ITIH3), was progressively lower in severe non-alcoholic fatty liver disease (NAFLD) disease states highlighting an inverse relationship between Itih3/ITIH3 expression and NAFLD severity. Follow-up animal and cell culture models demonstrated that hepatic ITIH3 overexpression lowered liver triglyceride and lipid droplet accumulation, respectively. Conversely, ITIH3 knockdown in mice increased the liver triglyceride in two independent NAFLD models. Mechanistically, ITIH3 reduced mitochondrial respiration and this, in turn, reduced liver triglycerides, via downregulated de novo lipogenesis. This was accompanied by increased STAT1 signaling and Stat3 expression, both of which are known to protect against NAFLD/NASH. Our findings indicate hepatokine ITIH3 as a potential biomarker and/or treatment for NAFLD.
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Background/Objectives: The balance between regulatory and Th17 cells plays an important role in maintaining the immune tolerance after kidney transplantation (KTx) which is essential for transplantation success, defined as a long graft survival and an absence of organ rejection. The present study aimed to assess whether the pretransplant characteristics of IL-17A and IL-17F, their receptors, as well as miR-146a-5p, an miRNA associated with IL-17A/F regulation, can predict KTx outcomes. Methods: A group of 108 pre-KTx dialysis patients and 125 healthy controls were investigated for single nucleotide substitutions within genes coding for IL-17A, IL-17F, their IL-17RA/RC receptors, and miR-146a-5p. Genotyping was performed using LightSNiP assays. In addition, IL17-A/F serum concentrations were determined using ELISA while miR-146a-5p expression was analyzed by RT-PCR. Results: The IL-17F (rs763780) G allele prevailed in KTx recipients as compared to healthy individuals (OR = 23.59, p < 0.0001) and was associated with a higher IL-17F serum level (p = 0.0381) prior to transplantation. Higher miR-146a-5p expression before KTx was more frequently detected in recipients with an increased IL-17A serum concentration (p = 0.0177). Moreover, IL-17A (rs2275913) GG homozygosity was found to be associated with an increased incidence of deaths before KTx (OR = 4.17, p = 0.0307). T-cell or acute rejection episodes were more frequently observed among patients with the C allele of miR-146a-5p (rs2910164) (OR = 5.38, p = 0.0531). IL17-RA/-RC genetic variants (p < 0.05) seem to be associated with eGFR values. Conclusions: These results imply that IL-17F (rs763780) polymorphism is associated with the serum level of this cytokine and may be related to the risk of renal disease and transplant rejection together with miR-146a-5p (rs2910164), while the IL-17A (rs2275913) genotype may affect patients' survival before KTx.
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Aspergilose , Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Evolução Fatal , Aspergilose/tratamento farmacológico , Aspergilose/etiologia , Aspergilose/diagnóstico , Masculino , Pessoa de Meia-Idade , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/etiologia , Hospedeiro ImunocomprometidoRESUMO
BACKGROUND/AIM: Tremor is common with tacrolimus treatment and is linked with peak blood drug concentrations. We investigated the effect of switching from immediate-release tacrolimus (IR-TAC) to MeltDose prolonged-release tacrolimus (LCPT) on tremor in kidney transplant recipients experiencing tremor at therapeutic levels of IR-TAC. METHODS: The Activities of Daily Living Subscale (ADL, range 0-48, lower = better) of the Essential Tremor Rating Scale was used to assess the effect of therapy change on speech, occupational impairment and social activities over a 12-month follow-up period. RESULTS: The study included 18 patients (mean age = 45.6 y, range 26-73; median (IQR) time from transplant = 1.1 y (0.6-1.5), with baseline IR-TAC trough concentrations (C0) ranging from 4.2 to 9.4 ng/mL (mean C0 = 6.7 ± 1.3 ng/mL). After the switch to LCPT, the mean ADL score improved from baseline 11.2 to 8.4 after 7 to 14 days (an 18% improvement, P < .001). This improvement was sustained after 3 months (ADL score = 5.0, 46% improvement vs baseline), 6 months (ADL score = 4.4, 48% improvement vs baseline), and 12 months (ADL score = 3.6, 63% improvement vs baseline); all P < .001. Despite a 40% reduction in LCPT daily doses (mean -1.9 mg/day compared to IR-TAC), the achieved C0 was constant during the course of the 12-month observation (P = .755). The renal function remained stable after conversion (eGFR 12 months vs baseline = +1.1 mL/min/1.73 m2, 95% CI: -5.6 to +7.9). CONCLUSION: Conversion to LCPT may alleviate symptom burden and improve daily activities in kidney transplant recipients experiencing tremor within therapeutic IR-TAC concentrations.
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Preparações de Ação Retardada , Imunossupressores , Transplante de Rim , Tacrolimo , Tremor , Humanos , Tacrolimo/administração & dosagem , Tacrolimo/uso terapêutico , Pessoa de Meia-Idade , Feminino , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Masculino , Adulto , Idoso , Atividades Cotidianas , Resultado do TratamentoRESUMO
Radiological procedures utilising intravascular contrast media (ICM) are fundamental to modern medicine, enhancing diagnostics and treatment in diverse medical fields. However, the application of ICM has been constrained in patients with compromised kidney function due to perceived nephrotoxic risks, called contrast-induced nephropathy or contrastinduced acute kidney injury. Historical evidence marked ICM as a possible contributor to kidney damage. This led to restrictive guidelines advocating limited ICM use in patients with impaired renal function, preventing crucial radiographic interventions in patients with acute kidney injury (AKI) and chronic kidney disease. Recent advances challenge these traditional views. In particular, no direct causal relationship has been confirmed between contrast admi-nistration and elevated serum creatinine concentrations in humans. Furthermore, contemporary research models and meta-analyses do not associate AKI with contrast usage. This paper, prepared by a cross-disciplinary team of nephrologists and radiologists, presents updated guidelines for ICM application amid renal function impairments, emphasising the reduced nephrotoxic risks currently understood and loosening the previous restrictive approach in patients with renal dysfunction.
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Knowing about the antibiotic resistance, serotypes, and virulence-associated genes of Group B Streptococcus for epidemiological and vaccine development is very important. We have determined antimicrobial susceptibility patterns, serotype, and virulence profiles. The antibiotic susceptibility was assessed for a total of 421 Streptococcus agalactiae strains, isolated from pregnant women and neonates. Then, 89 erythromycin and/or clindamycin-resistant strains (82 isolates obtained from pregnant women and seven isolates derived from neonates) were assessed in detail. PCR techniques were used to identify the studied strains, perform serotyping, and assess genes encoding selected virulence factors. Phenotypic and genotypic methods determined the mechanisms of resistance. All tested strains were sensitive to penicillin and levofloxacin. The constitutive MLSB mechanism (78.2%), inducible MLSB mechanism (14.9%), and M phenotype (6.9%) were identified in the macrolide-resistant strains. It was found that macrolide resistance is strongly associated with the presence of the ermB gene and serotype V. FbsA, fbsB, fbsC, scpB, and lmb formed the most recurring pattern of genes among the nine surface proteins whose genes were analysed. A minority (7.9%) of the GBS isolates exhibited resistance to lincosamides and macrolides, or either, including those that comprised the hypervirulent clone ST-17. The representative antibiotic resistance pattern consisted of erythromycin, clindamycin, and tetracycline resistance (71.9%). An increase in the fraction of strains resistant to macrolides and lincosamides indicates the need for monitoring both the susceptibility of these strains and the presence of the ST-17 clone.
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Antibacterianos , Infecções Estreptocócicas , Recém-Nascido , Feminino , Humanos , Gravidez , Antibacterianos/farmacologia , Macrolídeos/farmacologia , Streptococcus agalactiae , Clindamicina/farmacologia , Gestantes , Polônia/epidemiologia , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/epidemiologia , Farmacorresistência Bacteriana/genética , Testes de Sensibilidade Microbiana , Lincosamidas/farmacologia , Eritromicina/farmacologiaRESUMO
Global interest in applying virtual reality (VR) in research and medicine has grown significantly, with potential benefits for patients suffering from balance disorders, instability, and a high risk of falling. This exploratory study assesses the impact of immersive VR (IVR) delivered through a head-mounted display (HMD) on balance and explores the feasibility of using the HMD VR unit as a standalone posturography tool. Using the Meta Quest 2 HMD and a mid-range Android smartphone equipped with standard sensors, the research employed a VR environment that simulated a ship at sea, with thirty-eight healthy participants with no otoneurologic abnormalities. Measurements were conducted in repeated trials, including static assessments on both stable ground and foam, as well as a 3-m walk. This was conducted in two settings: one within a VR environment with three different intensity levels and the other in non-VR settings. Statistical analysis and clinical evaluation revealed that IVR with HMD influences head-level sway velocity, which correlates with increased visual disturbance, suggesting its potential as a low-risk standalone posturography tool.
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Realidade Virtual , Humanos , Estudos de Viabilidade , Smartphone , CaminhadaRESUMO
AIMS/HYPOTHESIS: Body niche-specific microbiota in maternal-neonatal dyads from gravidae with type 1 diabetes have not been quantitatively and functionally examined. Similarly, the impact of pregnancy-specific factors, such as the presence of comorbidities known to occur more frequently among gravidae with type 1 diabetes, including Caesarean delivery, as well as antibiotic prophylaxis, level of glycaemic control during each trimester of pregnancy and insulin administration, has not been adequately considered. The aims of this study were to characterise the maternal and neonatal microbiomes, assess aspects of microbiota transfer from the maternal microbiomes to the neonatal microbiome and explore the impact of type 1 diabetes and confounding factors on the microbiomes. METHODS: In this observational case-control study, we characterised microbiome community composition and function using 16S rRNA amplicon sequencing in a total of 514 vaginal, rectal and ear-skin swabs and stool samples derived from 92 maternal-neonatal dyads (including 50 gravidae with type 1 diabetes) and in-depth clinical metadata from throughout pregnancy and delivery. RESULTS: Type 1 diabetes-specific microbiota were identified among gravidae with type 1 diabetes and their neonates. Neonatal microbiome profiles of ear-skin swabs and stool samples were established, indicating the taxa more prevalent among neonates born to mothers with type 1 diabetes compared with neonates born to control mothers. Without taking into account the type 1 diabetes status of mothers, both delivery mode and intrapartum antibiotic prophylaxis were found to have an influence on neonatal microbiota composition (both p=0.001). In the logistic regression analysis involving all confounding variables, neonatal ear-skin microbiome variation was explained by maternal type 1 diabetes status (p=0.020) and small for gestational age birthweight (p=0.050). Moreover, in women with type 1 diabetes, a relationship was found between HbA1c levels >55 mmol/mol (>7.2%) measured in the first trimester of pregnancy and neonatal ear-skin microbiota composition (p=0.008). In the PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) assessment, pathways concerning carbohydrate biosynthesis were predicted as key elements of the microbial functional profiles dysregulated in type 1 diabetes. Additionally, in SourceTracker analysis, we found that, on average, 81.0% of neonatal microbiota was attributed to maternal sources. An increase in the contribution of maternal rectum microbiota and decrease in the contribution of maternal cervix microbiota were found in ear-skin samples of vaginally delivered neonates of mothers with type 1 diabetes compared with neonates born to control mothers (83.2% vs 59.5% and 0.7% vs 5.2%, respectively). CONCLUSIONS/INTERPRETATION: These findings indicate that, in addition to maternal type 1 diabetes, glycaemic dysregulation before/in the first trimester of pregnancy, mode of delivery and intrapartum antibiotic prophylaxis may contribute to the inoculation and formation of the neonatal microbiomes. DATA AVAILABILITY: The BioProject (PRJNA961636) and associated SRA metadata are available at http://www.ncbi.nlm.nih.gov/bioproject/961636 . Processed data on probiotic supplementation and the PICRUSt analysis are available in the Mendeley Data Repository ( https://doi.org/10.17632/g68rwnnrfk.1 ).
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Diabetes Mellitus Tipo 1 , Microbiota , Recém-Nascido , Gravidez , Humanos , Feminino , RNA Ribossômico 16S/genética , Estudos de Casos e Controles , Filogenia , Microbiota/genéticaRESUMO
OBJECTIVE: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is the most prevalent liver disease globally, yet no therapies are approved. The effects of Escherichia coli Nissle 1917 expressing aldafermin, an engineered analog of the intestinal hormone FGF19, in combination with dietary change were investigated as a potential treatment for MASLD. METHODS: MASLD was induced in C57BL/6J male mice by American lifestyle-induced obesity syndrome diet and then switched to a standard chow diet for seven weeks. In addition to the dietary change, the intervention group received genetically engineered E. coli Nissle expressing aldafermin, while control groups received either E. coli Nissle vehicle or no treatment. MASLD-related plasma biomarkers were measured using an automated clinical chemistry analyzer. The liver steatosis was assessed by histology and bioimaging analysis using Fiji (ImageJ) software. The effects of the intervention in the liver were also evaluated by RNA sequencing and liquid-chromatography-based non-targeted metabolomics analysis. Pathway enrichment studies were conducted by integrating the differentially expressed genes from the transcriptomics findings with the metabolites from the metabolomics results using Ingenuity pathway analysis. RESULTS: After the intervention, E. coli Nissle expressing aldafermin along with dietary changes reduced body weight, liver steatosis, plasma aspartate aminotransferase, and plasma cholesterol levels compared to the two control groups. The integration of transcriptomics with non-targeted metabolomics analysis revealed the downregulation of amino acid metabolism and related receptor signaling pathways potentially implicated in the reduction of hepatic steatosis and insulin resistance. Moreover, the downregulation of pathways linked to lipid metabolism and changes in amino acid-related pathways suggested an overall reduction of oxidative stress in the liver. CONCLUSIONS: These data support the potential for using engineered microbial therapeutics in combination with dietary changes for managing MASLD.
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Escherichia coli , Hepatopatia Gordurosa não Alcoólica , Masculino , Camundongos , Animais , Escherichia coli/metabolismo , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo , Dieta , Redes e Vias Metabólicas , Aminoácidos/metabolismoRESUMO
Peripheral neurological complications are seen after SARS-CoV-2 infections. These are mostly immune-mediated such as Guillaine-Barré syndrome or chronic inflammatory demyelinating polyneuropathy. We present a 39-year-old man treated with a right sciatic nerve allotransplantation with subsequent clinical and electrophysiological improvement within 30 months of observation. After SARS-CoV-2 infection, he developed clinical deterioration with selective sciatic nerve demyelination in a nerve conduction study. Nerve conduction velocity returned to previous values within six months of treatment. Intravenous immunoglobulins were used at standard dosage. The inflammatory immune process seemed to be a cause of peripheral demyelination isolated to a nerve allograft with good reaction for intravenous immunoglobulin treatment.
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The lack of empathy towards disability is a significant societal issue that hampers inclusivity and understanding. Many struggle to comprehend the daily challenges and experiences faced by people with disabilities, leading to ignorance, prejudice, and exclusion. However, empathy plays a pivotal role in addressing this problem and serves as the foundation for developing and creating better products, services, and environments. This article explores the potential of developing virtual reality (VR) applications to enhance students' empathy towards individuals with disabilities. By increasing empathy levels, students are expected to gain significant qualifications in universal design (UD). The full application development process covers the most suitable head-mounted display (HMD) set. The implementation methodology using the Unity programming platform, the approach adopted for conducting classes using the developed VR application, and the deployment stage. Testing was successfully conducted on a student population, receiving positive user feedback. Through the integration of VR technology, the authors thoroughly describe how to address the empathy gap and equip students with essential skills for inclusive and accessible design. The findings presented in this study provide valuable guidance for educators and developers interested in harnessing VR's potential to foster empathy and advance universal design practices. With the presented methodology and proposed application, the authors demonstrate the effectiveness of VR applications in elevating students' empathy levels, consequently enhancing their qualifications in universal design. Med Pr. 2023;74(3):199-210.
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Empatia , Realidade Virtual , Humanos , Desenho Universal , EstudantesRESUMO
This article explores the relevance of universal design and empathic design in education. The universal design focuses on creating accessible and usable products, environments, and systems for individuals with diverse abilities. Empathy, on the other hand, involves understanding and sharing the feelings of others, encompassing cognitive, emotional, and compassionate empathy. The article investigates the application of empathy in design, particularly its importance for engineers. Teaching empathy to engineers is emphasized as a crucial aspect. By developing empathic skills, engineers gain a deeper understanding of user needs and perspectives, leading to more inclusive and user-centered design solutions. Effective communication techniques such as asking open-ended questions, active listening, observation, and perspective-taking are explored to enhance empathy in communication. The article also explores methods for measuring empathy, thus enabling engineers to assess the effectiveness of their empathic design approaches. The challenges facing students, teachers, and university authorities in implementing such courses are also bulleted. Med Pr. 2023;74(3):211-25.
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Pessoal de Educação , Desenho Universal , Humanos , Empatia , Emoções , EscolaridadeRESUMO
This case report describes a 59-year-old male patient after heart and kidney transplantation, subsequently diagnosed with refractory hypertension since implemented antihypertensive pharmacotherapy consisting of six agents did not provide a substantial therapeutic response. Elevated blood pressure and its impact on a hypertrophied transplanted heart and impaired renal graft function have led to a significant deterioration in the patient's cardiovascular risk profile. To address this issue, a native renal arteries denervation was performed. It resulted in a noteworthy decrease in both systolic and diastolic pressure values, thus manifesting a positive hypotensive effect. Furthermore, a sustainable reduction of left ventricular mass and stabilization in kidney graft function were noticed. The presented case provides evidence that renal denervation can be an efficacious complementary treatment method in individuals who received kidney and heart grafts as it leads to a decrease in cardiovascular risk.
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BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) is a complex disease involving both genetic and environmental factors in its onset and progression. We analyzed NASH phenotypes in a genetically diverse cohort of mice, the Hybrid Mouse Diversity Panel, to identify genes contributing to disease susceptibility. METHODS: A "systems genetics" approach, involving integration of genetic, transcriptomic, and phenotypic data, was used to identify candidate genes and pathways in a mouse model of NASH. The causal role of Matrix Gla Protein (MGP) was validated using heterozygous MGP knockout (Mgp+/-) mice. The mechanistic role of MGP in transforming growth factor-beta (TGF-ß) signaling was examined in the LX-2 stellate cell line by using a loss of function approach. RESULTS: Local cis-acting regulation of MGP was correlated with fibrosis, suggesting a causal role in NASH, and this was validated using loss of function experiments in 2 models of diet-induced NASH. Using single-cell RNA sequencing, Mgp was found to be primarily expressed in hepatic stellate cells and dendritic cells in mice. Knockdown of MGP expression in stellate LX-2 cells led to a blunted response to TGF-ß stimulation. This was associated with reduced regulatory SMAD phosphorylation and TGF-ß receptor ALK1 expression as well as increased expression of inhibitory SMAD6. Hepatic MGP expression was found to be significantly correlated with the severity of fibrosis in livers of patients with NASH, suggesting relevance to human disease. CONCLUSIONS: MGP regulates liver fibrosis and TGF-ß signaling in hepatic stellate cells and contributes to NASH pathogenesis.