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Upon encountering allergens, CD4+ T cells differentiate into IL-4-producing Th2 cells in lymph nodes, which later transform into polyfunctional Th2 cells producing IL-5 and IL-13 in inflamed tissues. However, the precise mechanism underlying their polyfunctionality remains elusive. In this study, we elucidate the pivotal role of NRF2 in polyfunctional Th2 cells in murine models of allergic asthma and in human Th2 cells. We found that an increase in reactive oxygen species (ROS) in immune cells infiltrating the lungs is necessary for the development of eosinophilic asthma and polyfunctional Th2 cells in vivo. Deletion of the ROS sensor NRF2 specifically in T cells, but not in dendritic cells, significantly abolished eosinophilia and polyfunctional Th2 cells in the airway. Mechanistically, NRF2 intrinsic to T cells is essential for inducing optimal oxidative phosphorylation and glycolysis capacity, thereby driving Th2 cell polyfunctionality independently of IL-33, partially by inducing PPARγ. Treatment with an NRF2 inhibitor leads to a substantial decrease in polyfunctional Th2 cells and subsequent eosinophilia in mice and a reduction in the production of Th2 cytokines from peripheral blood mononuclear cells in asthmatic patients. These findings highlight the critical role of Nrf2 as a spatial and temporal metabolic hub that is essential for polyfunctional Th2 cells, suggesting potential therapeutic implications for allergic diseases.
Assuntos
Asma , Fator 2 Relacionado a NF-E2 , Células Th2 , Animais , Feminino , Humanos , Camundongos , Asma/imunologia , Asma/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Eosinofilia/imunologia , Eosinofilia/metabolismo , Glicólise , Interleucina-33/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 2 Relacionado a NF-E2/metabolismo , Fosforilação Oxidativa , PPAR gama/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células Th2/imunologia , Células Th2/metabolismoRESUMO
Liver X receptor (LXR) is a critical regulator of cholesterol homeostasis that inhibits T cell receptor (TCR)-induced proliferation by altering intracellular sterol metabolism. However, the mechanisms by which LXR regulates helper T cell subset differentiation remain unclear. Here, we demonstrate that LXR is a crucial negative regulator of follicular helper T (Tfh) cells in vivo. Both mixed bone marrow chimera and antigen-specific T cell adoptive cotransfer studies show a specific increase in Tfh cells among LXRß-deficient CD4+ T cell population in response to immunization and lymphocytic choriomeningitis mammarenavirus (LCMV) infection. Mechanistically, LXRß-deficient Tfh cells express augmented levels of T cell factor 1 (TCF-1) but comparable levels of Bcl6, CXCR5, and PD-1 in comparison with those of LXRß-sufficient Tfh cells. Loss of LXRß confers inactivation of GSK3ß induced by either AKT/Extracellular signal-regulated kinase (ERK) activation or Wnt/ß-catenin pathway, leading to elevated TCF-1 expression in CD4+ T cells. Conversely, ligation of LXR represses TCF-1 expression and Tfh cell differentiation in both murine and human CD4+ T cells. LXR agonist significantly diminishes Tfh cells and the levels of antigen-specific IgG upon immunization. These findings unveil a cell-intrinsic regulatory function of LXR in Tfh cell differentiation via the GSK3ß-TCF1 pathway, which may serve as a promising target for pharmacological intervention in Tfh-mediated diseases.
Assuntos
Células T Auxiliares Foliculares , Linfócitos T Auxiliares-Indutores , Camundongos , Humanos , Animais , Receptores X do Fígado/genética , Receptores X do Fígado/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Centro Germinativo , Fator 1 de Transcrição de Linfócitos T/genética , Diferenciação CelularRESUMO
In this study, a molecular beacon (MB) was designed for colorimetric loop-mediated isothermal amplification (cLAMP). The length of complementary bases on the MB, guanine and cytosine content (GC content), and hybridization sites of complementary bases were investigated as key factors affecting the design of the MB. We designed MBs consisting of 10, 15, and 20 complementary bases located at both ends of the HRPzyme. In the case of the long dumbbell DNA structure amplified from the hlyA gene of Listeria monocytogenes, possessing a flat region (F1c-B1) of 61 base pairs (bp), an MB was designed to intercalate into the flat region between the F1c and B1 regions of the LAMP amplicons. In the case of the short dumbbell DNA structure amplified from the bcfD gene of Salmonella species possessing a flat region (F1c-B1) length of 6 bp, another MB was designed to intercalate into the LoopF or LoopB regions of the LAMP amplicons. The results revealed that the hybridization site of the MB on the LAMP amplicons was not crucial in designing the MB, but the GC content was an important factor. The highest hybridization efficiencies for LAMP amplicons were obtained from hlyA gene-specific and bcfD gene-specific MBs containing 20- and 15-base complementary sequences, respectively, which exhibited the highest GC content. Therefore, designing MBs with a high GC content is an effective solution to overcome the low hybridization efficiency of cLAMP assays. The results obtained can be used as primary data for designing MBs to improve cLAMP accessibility.
Assuntos
Colorimetria , Listeria monocytogenes , Técnicas de Amplificação de Ácido Nucleico , Técnicas de Amplificação de Ácido Nucleico/métodos , Colorimetria/métodos , Listeria monocytogenes/genética , Listeria monocytogenes/isolamento & purificação , DNA Bacteriano/genética , DNA Bacteriano/análise , Salmonella/genética , Salmonella/isolamento & purificação , Hibridização de Ácido Nucleico/métodos , Técnicas de Diagnóstico MolecularRESUMO
Contamination by Escherichia coli O157:H7 is considered a threat in the livestock and food industries. Therefore, it is necessary to develop methods for the convenient and rapid detection of Shiga-toxin-producing E. coli O157:H7. This study aimed to develop a colorimetric loop-mediated isothermal amplification (cLAMP) assay using a molecular beacon to rapidly detect E. coli O157:H7. Primers and a molecular beacon were designed for targeting the Shiga-toxin-producing virulence genes (stx1 and stx2) as molecular markers. Additionally, Bst polymerase concentration and amplification conditions for bacterial detection were optimized. The sensitivity and specificity of the assay were also investigated and validated on artificially tainted (100-104 CFU/g) Korean beef samples. The cLAMP assay could detect 1 × 101 CFU/g at 65 °C for both genes, and the assay was confirmed to be specific for E. coli O157:H7. The cLAMP takes about an hour and does not require expensive devices (e.g., thermal cycler and detector). Hence, the cLAMP assay proposed herein can be used in the meat industry as a fast and simple way to detect E. coli O157:H7.
Assuntos
Escherichia coli O157 , Animais , Bovinos , Escherichia coli O157/genética , Colorimetria , Técnicas de Amplificação de Ácido Nucleico/métodos , Técnicas de Diagnóstico Molecular/métodos , Microbiologia de AlimentosRESUMO
BACKGROUND: Whole-exome sequencing-based diagnosis of rare diseases typically yields 40%-50% of success rate. Precise diagnosis of the patients with neuromuscular disorders (NMDs) has been hampered by locus heterogeneity or phenotypic heterogeneity. We evaluated the utility of transcriptome sequencing as an independent approach in diagnosing NMDs. METHODS: The RNA sequencing (RNA-Seq) of muscle tissues from 117 Korean patients with suspected Mendelian NMD was performed to evaluate the ability to detect pathogenic variants. Aberrant splicing and CNVs were inspected to identify additional causal genetic factors for NMD. Aberrant splicing events in Dystrophin (DMD) were investigated by using antisense oligonucleotides (ASOs). A non-negative matrix factorisation analysis of the transcriptome data followed by cell type deconvolution was performed to cluster samples by expression-based signatures and identify cluster-specific gene ontologies. RESULTS: Our pipeline called 38.1% of pathogenic variants exclusively from the muscle transcriptomes, demonstrating a higher diagnostic rate than that achieved via exome analysis (34.9%). The discovery of variants causing aberrant splicing allowed the application of ASOs to the patient-derived cells, providing a therapeutic approach tailored to individual patients. RNA-Seq data further enabled sample clustering by distinct gene expression profiles that corresponded to clinical parameters, conferring additional advantages over exome sequencing. CONCLUSION: The RNA-Seq-based diagnosis of NMDs achieves an increased diagnostic rate and provided pathogenic status information, which is not easily accessible through exome analysis.
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Doenças Neuromusculares , Transcriptoma , Humanos , Transcriptoma/genética , Distrofina/genética , RNA Mensageiro/genética , Doenças Neuromusculares/diagnóstico , Doenças Neuromusculares/genética , Oligonucleotídeos AntissensoRESUMO
BACKGROUND: This study validated the Korean version of the Readiness to Return to Work (RRTW) scale, as an assessment measure, following a musculoskeletal, work-related injury and as a measure of following return to work. METHODS: The participants of this study were workers with experience in rehabilitation programs at the Workers' Compensation and Welfare Service (KCOMWEL) Hospital in Korea. Factor analyses were employed to ensure the validity and reliability of the RRTW scale in claimants who were in treatment without working (the not-working group) or who had already returned to work (the working group). To test structural validity, we analyzed exploratory factor analysis (EFA) respectively for the not working group (exploratory factor analysis (EFA) (n = 200), confirmatory factor analysis (CFA) (n = 109), and the working group (n = 123). To verify concurrent validity (multidimensional and assignment approach), the variables that were identified as relevant variables in previous studies were analyzed. RESULTS: The not working group EFA, as shown in the original scale, had four dimensions, and one item was deleted: (1) Precontemplation (PC), (2) Contemplation (C), (3) Prepared for Action-Self-evaluative (PAS), and (4) Prepared for Action-Behavioral (PAB). The CFA revealed that a good model fit and reliability were suitable. Regarding the working group of EFA, it appeared in two dimensions as in the original scale, one item was modified from the UM scale to the PM scale, and the reliability was appropriate. Concurrent validity was satisfied based on the correlation between the RRTW factor and related variables. CONCLUSIONS: RRTW in the Korean version of the instrument was similar to those reported for the original scale, indicating that it may be used in research and clinical settings.
Assuntos
Doenças Musculoesqueléticas , Retorno ao Trabalho , Humanos , Psicometria , Reprodutibilidade dos Testes , Indenização aos Trabalhadores , República da Coreia , Doenças Musculoesqueléticas/reabilitação , Inquéritos e QuestionáriosRESUMO
Heat stress (HS) affects cell culture as well as animal production. Although there have been many reports on the disparate effects of heat stress, its effects on mammalian muscle stem cells are still unclear. In this study, we isolated porcine muscle satellite cells (PMSCs) from the femurs of 1-day-old piglets, and cultured them under three temperature conditions: 37 °C, 39 °C, and 41 °C. Exposure to HS not only decreased the viability and proliferation rates of PMSCs, but also regulated the cell cycle and induced apoptosis. High-temperature culture conditions decreased both protein and gene expression of Pax7, a proliferation and maintenance marker of muscle satellite cells, whereas it increased both protein and gene expression of MyoG, a differentiation marker, and promoted myotube formation in the early stage of differentiation induction. In addition, the protein and gene expression of several heat shock proteins (HSPs) in PMSCs increased due to heat treatment. In conclusion, HS induced the cell cycle arrest of PMSCs, thereby reducing the proliferation rate. In addition, high-temperature culture conditions promoted the formation of myotubes at the early stage of differentiation of PMSCs without additives.
Assuntos
Células Satélites de Músculo Esquelético , Suínos , Animais , Células Satélites de Músculo Esquelético/metabolismo , Resposta ao Choque Térmico/fisiologia , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Mamíferos , Células CultivadasRESUMO
Background: The coronavirus disease 2019 pandemic has expanded noncontact health care systems worldwide. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technology that enables treatment monitoring under remote supervision. We investigated the factors affecting patients' decision to participate in telerehabilitation (TR) using tDCS for motor function recovery after suffering a stroke. Materials and Methods: Four medical institutions surveyed 156 patients with poststroke paralysis. The participants were asked whether they would participate in TR therapy using tDCS in the future. We performed logistic regression analysis to examine the factors-demographic data, stroke characteristics, arm function, gait, and cognitive function-that influenced participants' decisions. Results: Of the participants, 66% (103/156) reported that they would participate in TR using tDCS in the future. Participants' monthly salary was a single significant independent factor influencing their decision to participate. Those earning greater than 5 million KRW (4,000 USD) were more likely to engage in TR via tDCS than those earning less than 1 million KRW (800 USD). The most common barriers to participation in telemedicine included the preference for face-to-face treatment and unfamiliarity. The expected medical expenses of TR using tDCS were 46,154 KRW (37 USD) per session. Conclusions: Most participants with poststroke paralysis responded positively to TR using tDCS for hand function recovery. For telemedicine to work effectively in a situation wherein face-to-face rehabilitation is impossible, prior discussion at the governmental level is essential for determining medical finances.
Assuntos
COVID-19 , Acidente Vascular Cerebral , Telerreabilitação , Estimulação Transcraniana por Corrente Contínua , Humanos , COVID-19/epidemiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , ParalisiaRESUMO
The phenotypic effect of the knockdown/out of AGAMOUS clade MADS-box gene SlMBP3 in tomato was evaluated using a transferred DNA (T-DNA)-tagged mutant of SlMBP3 and SlMBP3-RNA interference lines. SlMBP3 was preferentially expressed in the locular tissue of fruit and the seed coat combined with the endoderm. Consistent with where SlMBP3 is expressed, the SlMBP3-knockout/down lines showed non-liquefied locular tissues and increased number of seed hairs than the wild type (WT). The early cell degradation of the locular tissue was not observed in the fruits of the SlMBP3-knockout/down lines, and the cells were elongated like placental cells resulting in non-liquefied locular tissues. As the result, the fruits of the SlMBP3-knockout/down lines exhibited higher dry matter contents and titratable acidity than those of the WT. During locular tissue cell development under the SlMBP3 knockout/down, the expression of cell-enlargement-related genes (beta-expansin gene SlEXPB1 and endo-beta-1,4-D-glucanase gene Cel8) and pectinase-inhibitor-related genes (pectin esterase inhibitor gene PE inhibitor and polygalacturonase inhibitor gene PG inhibitor) was upregulated and that of pectinase-encoding genes (polygalacturonase gene QRT3-like and pectin lyase gene PL2) was downregulated. In the seed coat of the SlMBP3-knockout/down lines, tomato trichome-formation-related genes such as MYB genes containing R2 and R3 repeats (R2R3-MYB) transcription factor SlMYB75, B-type cyclin SlCycB2 and Homeodomain Leucine Zipper (HD-Zip) IV transcription factor Woolly were downregulated. Our results demonstrate that SlMBP3 is involved in the liquefaction of the locular tissue through the modification of cell development and degradation processes and seed hair formation in tomato fruits, and the SlMBP3 knockout/down results in normal-sized fruit with increased dry matter content.
Assuntos
Solanum lycopersicum , Gravidez , Feminino , Humanos , Solanum lycopersicum/metabolismo , Frutas/metabolismo , Poligalacturonase/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Placenta/metabolismo , Parede Celular/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Noroviruses (NoVs) are the most common causes of epidemic gastroenteritis, responsible for at least 50% of all gastroenteritis outbreaks worldwide and significant causes of foodborne illness. In the USA, approximately 21 million illnesses attributable to NoVs have annually occurred. Therefore, there is a great demand to develop a rapid, low-cost, and accurate detection method for NoVs. This study first reported colorimetric helicase-dependent amplification (HDA) methods based on specific primers integrated with HRPzyme for the rapid and sensitive detection of NoV GI and GII. The colorimetric HDA methods exhibited a detection limit of 10 copies mL-1 of each NoV GI and GII and were confirmed to be specific to each NoV GI and GII. The period required to complete the HDA method was 2 h, including a step of RNA extraction and cDNA synthesis without expensive instruments such as a thermal cycler and detector. The cutoff value of the method for the oyster artificially inoculated with a known amount of NoV was all 102 copies g-1 for NoV GI and GII. Therefore, the HDA method developed in this study can be useful tool for the on-site detection of NoVs in food samples.
Assuntos
Infecções por Caliciviridae , Gastroenterite , Norovirus , Infecções por Caliciviridae/diagnóstico , Infecções por Caliciviridae/epidemiologia , Colorimetria , Primers do DNA/genética , Gastroenterite/epidemiologia , Genótipo , Humanos , Norovirus/genética , Filogenia , RNA Viral/genéticaRESUMO
OBJECTIVE: This study aimed to establish whether the increased fetal pulmonary venous pulsatility index (PVPI) in late pregnancy can independently predict small for gestational age (SGA) and to verify its cut point value and efficacy. METHOD: The PVPI was measured in women with singleton pregnancies between 25 and 39 gestational weeks. Maternal hypertension and diabetes, estimated fetal weight (EFW) and percentile of the corresponding weeks of pregnancy (USG_PER), gestational weeks at delivery, and birth weight and percentile of the corresponding weeks of pregnancy (BABY_PER) were reviewed. To assess whether PVPI was independently correlated with BABY_PER, Pearson's correlation analysis was performed. The cut point value of PVPI for the prediction of SGA was established using a receiver operating characteristic (ROC) curve. RESULTS: A total of 129 mothers were included in this study. Both USG_PER and PVPI were significantly related to SGA, independently (P <.001 and P = .004, respectively). The cut point value of PVPI was found to be 1.13. The AUCs of PVPI and USG_PER were not significantly different (P = .624). The sensitivity of PVPI was 70.27%, and the specificity was 92.39%. CONCLUSION: PVPI could predict SGA independently, and the efficacy was comparable to EFW during pregnancy.
Assuntos
Veias Pulmonares , Feminino , Retardo do Crescimento Fetal , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Gravidez , Terceiro Trimestre da GravidezRESUMO
Smoking is a leading cause of diseases and death, with significant socioeconomic consequences. The purpose of this study was to evaluate the health and economic effectiveness of a workplace smoking cessation program. A total of 89 smokers from seven workplaces in Korea were the participants of the program. For 4 months, individual counseling based on the transtheoretical model (TTM) was conducted and interpersonal and organizational components were applied to encourage entire workplaces to encourage employee smoking cessation. The primary outcome was whether participants quit smoking or not. We also evaluated the changes in attitude and perceptions related to smoking cessation before and after the program and estimated the program's economic effects. Economic effects were defined as reductions in productivity losses and medical expenses. We calculated the return on investment (ROI) values representing the averted cost through the program compared to program cost. At the end of the program, 40.4% of participants quit smoking. Improvements were observed in TTM-based attitudes and perceptions. The mean reduction in productivity losses was estimated to be $187,609.94 for 2 yr and the mean reduction in medical expenses was $3,136.49 at 20 yr among seven workplaces. When accounting for these reductions, the ROI was 15.39 (ranging from -1.00 to 44.53). These effects were robust under various scenarios. The smoking cessation program should be expanded to a wider variety of workplaces. In the future, more sophisticated economic assessment methods should be developed and applied to facilitate workplace recruitment and attract management support.
Smoking is a major cause of disease and death with large socioeconomic costs. This study examined the effect of a workplace smoking cessation program on health perspective, and on productivity and profit. A total of 40.4% of participants quit smoking, and the perceptions on smoking were improved. Also, the program was revealed to have an average return on investment (ROI) of 15.39. This can be deemed as the program's economic effect is 15.39 times the program cost. We believe this kind of evaluation may help with the dissemination of workplace health promotion programs.
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Abandono do Hábito de Fumar , Humanos , Fumantes , Fumar , Abandono do Hábito de Fumar/métodos , Prevenção do Hábito de Fumar , Local de TrabalhoRESUMO
OBJECTIVE: To investigate the response of Caragana microphylla in salt condition, transcriptome analysis, differentially expressed genes (DEGs) comparison with Arabidopsis thaliana, and the chlorophyll content analysis were performed. RESULTS: Gene Ontology (GO) term, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of DEGs indicated that salt condition affected photosynthesis and chlorophyll in C. microphylla. The DEGs compared with salt responsive genes of A. thaliana indicated that C. microphylla's responses to salt differed greatly from those of the model plant and that the results also indicated up-regulated genes related to photosynthesis and chlorophyll in C. microphylla. Moreover, we confirmed that salt-treated C. microphylla increased chlorophyll content, and the genes of protoporphyrin IX downstream in chlorophyll biosynthesis were induced in the heatmap analysis. CONCLUSIONS: These results showed a similar pattern to some halophytes plants with increased chlorophyll at a certain salt concentration, and we assumed that C. microphylla also has a mechanism to adapt or tolerate moderate salt conditions.
Assuntos
Caragana , Estresse Salino/genética , Cloreto de Sódio/farmacologia , Transcriptoma/efeitos dos fármacos , Caragana/efeitos dos fármacos , Caragana/genética , Clorofila/metabolismo , Perfilação da Expressão Gênica , Fotossíntese/efeitos dos fármacos , Plantas Tolerantes a Sal/efeitos dos fármacos , Plantas Tolerantes a Sal/genéticaRESUMO
BACKGROUND: Previous studies that have focused on the challenges faced by female surgeons, such as the gender pay gap, gender biases, lower likelihood of promotion, and gender differences in the perception of discrimination against women, are reviewed. A more comprehensive understanding of explicit and implicit gender discrimination and experiences and perceptions of discrimination is needed. This study aims to determine the current prevalence and degree of gender discrimination in the Korean Surgical Society and to compare the experiences and perceptions of gender discrimination between male and female surgeons. METHODS: We analyzed 400 responses from a survey sent to all members of the Korean Surgical Society. This electronic survey included 16 items on experiences of gender discrimination and 17 items on perceptions of gender discrimination. We conducted χ² tests and binary logistic regression on the data regarding these experiences and perceptions of gender discrimination. RESULTS: Adjusted analyses found that female surgeons were more likely to experience gender discrimination than their male counterparts across all categories of discrimination. Further, adjusted analyses showed that female surgeons were more likely to confirm the presence of gender discrimination than male surgeons. CONCLUSION: Female surgeons were more likely to experience implicit and explicit gender biases and discrimination throughout all stages of their career progression. We also discovered significant gender differences in the perception of gender discrimination, as well as the experience of it. Changing the male-dominated culture and raising awareness of gender biases and discrimination among male surgeons are crucial steps toward addressing gender discrimination in surgery.
Assuntos
Sexismo/psicologia , Cirurgiões/psicologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Sociedades Médicas , Inquéritos e QuestionáriosRESUMO
PURPOSE: To investigate the relationship between bladder debris found on renal and bladder ultrasonography (RBUS) and the first febrile urinary tract infection (UTI) episode in children under 2 years old. METHODS: We retrospectively reviewed the data of children aged <2 years with the first febrile UTI. We recorded bladder debris on RBUS and other findings (blood test, urinalysis, and urine culture). Other RBUS findings (renal pelvis debris, renal parenchymal change, wall thickening, and renal collecting system [RCS] dilatation) were recorded. Patients were divided into the debris (D) and non-D groups. RESULTS: Of 128 patients (boys: girls = 81:47, mean age = 5.6 ± 4.2 months), 24 (18.8%) had bladder debris. The mean C-reactive protein (CRP) levels were higher in the D group (6.1 ± 4.0 vs 4.3 ± 3.5, P = .03). Twenty-one patients in the D group (87.5%) had hematuria (odds ratio = 3.706, 95% confidence interval = 1.035-13.267, P = .04). No significant differences were seen in the urine culture results between both groups. Significant associations were seen between bladder debris and other RBUS findings such as debris in renal pelvis, renal parenchymal change, and RCS wall thickening. CONCLUSION: Bladder debris on RBUS is a common finding in children aged <2 years during the first febrile UTI. Bladder debris was related to higher CRP levels, hematuria and sonographic findings, but not to urine culture results.
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Febre/complicações , Infecções Urinárias/complicações , Infecções Urinárias/diagnóstico por imagem , Pré-Escolar , Feminino , Hematúria/complicações , Humanos , Lactente , Rim/diagnóstico por imagem , Rim/patologia , Pelve Renal/diagnóstico por imagem , Pelve Renal/patologia , Masculino , Estudos Retrospectivos , Ultrassonografia , Infecções Urinárias/patologiaRESUMO
We address the inverse Frobenius-Perron problem: given a prescribed target distribution ρ, find a deterministic map M such that iterations of M tend to ρ in distribution. We show that all solutions may be written in terms of a factorization that combines the forward and inverse Rosenblatt transformations with a uniform map; that is, a map under which the uniform distribution on the d-dimensional hypercube is invariant. Indeed, every solution is equivalent to the choice of a uniform map. We motivate this factorization via one-dimensional examples, and then use the factorization to present solutions in one and two dimensions induced by a range of uniform maps.
RESUMO
Prostaglandin E2 (PGE2) plays a key role in inflammation-associated carcinogenesis. NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the oxidation of the 15(S)-hydroxyl group of PGE2 to generate 15-keto PGE2. 15-PGDH has been known as a tumor suppressor in various malignancies including colon cancer. However, the molecular mechanisms underlying the tumor-suppressive function of 15-PGDH remain largely unresolved. In this study, we found that 15-keto PGE2 upregulated the expression of heme oxygenase-1 (HO-1), a representative antioxidative and anti-inflammatory enzyme, at both transcriptional and translational levels, in human colon epithelial CCD 841 CoN cells. A redox-sensitive transcription factor, NF-E2-related factor (Nrf2) plays a critical role in the regulation of HO-1 and other cytoprotective proteins. 15-Keto PGE2 induced translocation of Nrf2 into the nucleus and antioxidant response element-driven luciferase activity. Furthermore, the silencing of the Nrf2 gene abolished 15-keto PGE2-induced HO-1 expression in CCD 841 CoN cells. 15-Keto PGE2 activated AKT signaling, and the pharmacological AKT inhibitor, LY294002 suppressed the 15-keto PGE2-induced HO-1 expression. 15-Keto PGE2 generates the reactive oxygen species which is suppressed by the general antioxidant N-acetyl-l-cysteine. N-acetyl-l-cysteine treatment attenuated the 15-keto PGE2-induced phosphorylation of GSK3ß, transcriptional activity of Nrf2, and subsequently HO-1 expression. However, 13,14-dihydro-15-keto PGE2 lacking the α,ß-unsaturated carbonyl moiety failed to induce intracellular production of reactive oxygen species, HO-1 expression and nuclear translocation of Nrf2. In conclusion, 15-keto PGE2 induces HO-1 expression through Nrf2 activation in human colon epithelial cells.
Assuntos
Colo/citologia , Dinoprostona/análogos & derivados , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/genética , Mucosa Intestinal/citologia , Fator 2 Relacionado a NF-E2/metabolismo , Morte Celular/efeitos dos fármacos , Dinoprostona/farmacologia , Ativação Enzimática/efeitos dos fármacos , Heme Oxigenase-1/biossíntese , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacosRESUMO
BACKGROUND: This study aimed to develop a Korean version of the Return-to-Work Self-Efficacy (RTWSE)-19 Scale using forward- and backward-translation and investigate the validity of the RTWSE Scale specifically for Korean workers with work-related injuries. METHODS: Participants were 202 injured workers who had filed a claim accepted by the workers' compensation system and had received medical rehabilitation at workers' compensation hospitals following a work-related musculoskeletal injury. Among these participants, 88.1% were male, 54.5% were over 45 years, 45.5% were manufacturing employees, and 54.5% were craft or machine operator and assemblers. The 19 item RTWSE-19 scale was developed by Shaw et al. and have three underlying subscales: (i) meeting job demands, (ii) modifying job tasks, and (iii) communicating needs to others. Statistical analysis included exploratory factor analysis (maximum likelihood estimation with oblique quartimin rotation), internal consistency reliability using Cronbach's alpha, and correlations with related measures: pain intensity; fear-avoidance beliefs; general health; depression; and general self-efficacy. RESULTS: Using exploratory factor analysis, three factors with 17 items were identified: meeting job demands, modifying job tasks, and communicating needs to others. The removal of two items in the modifying job tasks domain resulted in an increased reliability. The Korean version of the RTWSE-17 showed reasonable model fit (CFI = .963; TLI = .943; RMSEA = .068; SRMR = 0.029), satisfactory reliability (r = 0.925), no floor and ceiling effect, and construct validity. CONCLUSIONS: The Korean RTWSE-17 scale was found to possess good psychometric properties and could address different injury types ranging from fractures to amputations involved in sub-acute and rehabilitation phases in the Korean context. This study's findings provide insights for practitioners and researchers to return to work after rehabilitation in a Korean clinical and workplace setting.
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Traumatismos Ocupacionais/psicologia , Escalas de Graduação Psiquiátrica/normas , Retorno ao Trabalho/psicologia , Autoeficácia , Avaliação da Capacidade de Trabalho , Adulto , Comparação Transcultural , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismos Ocupacionais/reabilitação , Psicometria , Reprodutibilidade dos Testes , República da Coreia , Traduções , Indenização aos Trabalhadores , Adulto JovemRESUMO
OBJECTIVE: This study aimed to develop and validate an instrument that measures the attitudes of healthcare professionals toward persons with disabilities. DESIGN: The Delphi survey consensus method was used to compose a preliminary questionnaire for survey. Then, healthcare professionals responded to the questionnaire online, and the results were used for psychometric analysis. SETTING: Three tertiary hospitals. SUBJECTS: A total of 993 healthcare professionals. INTERVENTIONS: Not applicable. MAIN MEASURES: Attitudes of healthcare professionals toward persons with disabilities. RESULTS: A 28-item preliminary questionnaire was initially developed after a two-round Delphi survey with 16 experts. Through an online survey, the final 20 items were categorized as follows: behaviors in clinical situation, knowledge and skills, emotional response, and responsibility of healthcare professionals. The Cronbach's alpha coefficient for the total score was 0.890 and varied between 0.856 and 0.892 in the four subdomains. The newly developed tool showed an acceptable model fit. Healthcare professionals who participated in an education module showed higher scores in behavior and knowledge/skills subdomains than those who did not, whereas participants who had clinical experience with persons with disabilities demonstrated higher scores in emotional response and knowledge/skills subdomains. CONCLUSIONS: We developed a scale to measure the attitudes toward persons with disabilities of healthcare professionals. The scale demonstrated a sensitivity to measure a difference by participation in an education module or clinical experience with persons with disabilities.
Assuntos
Atitude do Pessoal de Saúde , Pessoas com Deficiência , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde/psicologia , Adulto , Técnica Delphi , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Sensibilidade e Especificidade , Inquéritos e QuestionáriosRESUMO
The experiments reported in this research paper aimed to determine the effect of supplementing different forms of L-methionine (L-Met) and acetate on protein synthesis in immortalized bovine mammary epithelial cell line (MAC-T cells). Treatments were Control, L-Met, conjugated L-Met and acetate (CMA), and non-conjugated L-Met and Acetate (NMA). Protein synthesis mechanism was determined by omics method. NMA group had the highest protein content in the media and CSN2 mRNA expression levels (P < 0.05). The number of upregulated and downregulated proteins observed were 39 and 77 in L-Met group, 62 and 80 in CMA group and 50 and 81 in NMA group from 448 proteins, respectively (P < 0.05). L-Met, NMA and CMA treatments stimulated pathways related to protein and energy metabolism (P < 0.05). Metabolomic analysis also revealed that L-Met, CMA and NMA treatments resulted in increases of several metabolites (P < 0.05). In conclusion, NMA treatment increased protein concentration and expression level of CSN2 mRNA in MAC-T cells compared to control as well as L-Met and CMA treatments through increased expression of milk protein synthesis-related genes and production of the proteins and metabolites involved in energy and protein synthesis pathways.