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Introduction: The global rise in ageing populations poses challenges for healthcare systems. By 2030, Singapore anticipates a quarter of its population to be aged 65 or older. This study addresses the dearth of research on frailty's impact on emergency laparotomy (EL) outcomes in this demographic, emphasising the growing significance of this surgical intervention. Method: Conducted at 2 tertiary centres in Singapore from January to December 2019, a retrospective cohort study examined EL outcomes in patients aged 65 or older. Frailty assessment, using the Clinical Frailty Scale (CFS), was integrated into demographic, diagnostic and procedural analyses. Patient data from Tan Tock Seng Hospital and Khoo Teck Puat Hospital provided a comprehensive view of frailty's role in EL. Results: Among 233 participants, 26% were frail, revealing a higher vulnerability in the geriatric population. Frail individuals exhibited elevated preoperative risk, prolonged ICU stays, and significantly higher 90-day mortality (21.3% versus 6.4%). The study illuminated a nuanced connection between frailty and adverse outcomes, underlining the critical need for robust predictive tools in this context. Conclusion: Frailty emerged as a pivotal factor influencing the postoperative trajectory of older adults undergoing EL in Singapore. The integration of frailty assessment, particularly when combined with established metrics like P-POSSUM, showcased enhanced predictive accuracy. This finding offers valuable insights for shared decision-making and acute surgical unit practices, emphasising the imperative of considering frailty in the management of older patients undergoing emergency laparotomy.
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Idoso Fragilizado , Fragilidade , Avaliação Geriátrica , Laparotomia , Humanos , Singapura/epidemiologia , Idoso , Feminino , Masculino , Estudos Retrospectivos , Laparotomia/estatística & dados numéricos , Laparotomia/métodos , Fragilidade/epidemiologia , Idoso de 80 Anos ou mais , Idoso Fragilizado/estatística & dados numéricos , Avaliação Geriátrica/métodos , Emergências , Tempo de Internação/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologiaRESUMO
An accurate method for qualitative and quantitative analysis of lipid-bound (LB), protein-bound (PB), oligosaccharides-bound, and free sialic acids in milk was developed by using high-performance liquid chromatography -triple quadrupole-tandem mass spectrometer. The profile of free and bound sialic acids in milk (human, bovine, goat, and sheep) and infant formula (IF) was examined in the present study. Human milk contains only N-acetylneuraminic acid (Neu5Ac) and was mainly present in the form of oligosaccharide-bound. The content of total Neu5Ac (T-Neu5Ac), free and bound Neu5Ac in human milk decreased with the prolongation of lactation. The most intriguing finding was the increase in the proportion of PB and LB sialic acids. The sialic acids in bovine and sheep milk were mainly PB and oligosaccharides-bound Neu5Ac. T-Neu5Ac in goat milk (GM) was 67.44-89.72 µg/mL and was mainly PB Neu5Ac, but total N-glycolylneuraminic acid (T-Neu5Gc) content of GM can be as high as 100.01 µg/mL. The concentration of T-Neu5Gc in sheep and GM was significantly higher than that of bovine milk (BM). T-Neu5Gc content of GM -based IF was 264.86 µg/g, whereas T-Neu5Gc content of BM -based IF was less (2.26-17.01 µg/g). Additionally, our results found that there were also sialic acids in IF ingredients, which were mainly bound with protein and oligosaccharides, primarily derived from desalted whey powder and whey protein concentrate.
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Cabras , Fórmulas Infantis , Leite Humano , Leite , Ácidos Siálicos , Espectrometria de Massas em Tandem , Animais , Bovinos , Cromatografia Líquida de Alta Pressão/métodos , Leite/química , Espectrometria de Massas em Tandem/métodos , Fórmulas Infantis/química , Humanos , Ovinos , Leite Humano/química , Ácidos Siálicos/análise , Ácido N-Acetilneuramínico/análise , Oligossacarídeos/análise , Lactente , Ácidos Neuramínicos/análise , FemininoRESUMO
BACKGROUND: In order to improve taVNS efficacy, the usage of fMRI to explore the predictive neuroimaging markers would be beneficial for screening the appropriate MDD population before treatment. METHODS: A total of 86 MDD patients were recruited in this study, and all subjects were conducted with the clinical scales and resting-state functional magnetic resonance imaging (fMRI) scan before and after 8 weeks' taVNS treatment. A two-stage feature selection strategy combining Machine Learning and Statistical was used to screen out the critical brain functional connections (FC) that were significantly associated with efficacy prediction, then the efficacy prediction model was constructed for taVNS treating MDD. Finally, the model was validated by separated the responding and non-responding patients. RESULTS: This study showed that taVNS produced promising clinical efficacy in the treatment of mild and moderate MDD. Eleven FCs were selected out and were found to be associated with the cortico-striatal-pallidum-thalamic loop, the hippocampus and cerebellum and the HAMD-17 scores. The prediction model was created based on these FCs for the efficacy prediction of taVNS treatment. The R-square of the conducted regression model for predicting HAMD-17 reduction rate is 0.44, and the AUC for classifying the responding and non-responding patients is 0.856. CONCLUSION: The study demonstrates the validity and feasibility of combining neuroimaging and machine learning techniques to predict the efficacy of taVNS on MDD, and provides an effective solution for personalized and precise treatment for MDD.
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Transtorno Depressivo Maior , Aprendizado de Máquina , Imageamento por Ressonância Magnética , Estimulação do Nervo Vago , Humanos , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/diagnóstico por imagem , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Estimulação do Nervo Vago/métodos , Avaliação de Resultados em Cuidados de Saúde , Resultado do Tratamento , Adulto Jovem , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Estimulação Elétrica Nervosa Transcutânea/métodosRESUMO
Riparian woodlands prevent bank erosions, recycle minerals, sustain biodiversity, act as flow resistance on floodplains, and filter pollutants. The emergent trees characterize woodlands with different spacing arrangements that dictate flow resistance and longitudinal dispersion of the pollutants in compound channel flow. The single- and multistage compound channels exist in urban and natural watercourses with riparian and transplanted trees on different stages of the floodplain. This study numerically validates the planting of vegetation in lines on single- and multistage floodplains using a wall-modeled large-eddy simulation model. Post-validation, the focus of the study was to assess the hydrodynamic behavior and mixing around the floodplain and main channel section of different tested configurations. The approximation of flow structures for the various configurations of tree plantations shows stronger vortices with significant characteristic length scales for floodplains closer to the main channel. The intensity of the secondary current is higher for denser planted trees at junctions of floodplains. For higher flow events, drag force contributions for staged floodplains with trees on both stages are 45-41%, and trees on the top stage contribute 27-22% to the total frictional force budget. The subsequent investigation shows that the in-line trees geometrical configuration and spacing arrangement on the floodplain dictates flow resistance and longitudinal dispersion of the pollutants and contamination in channel flow. The results show that the overall reduction in discharge for floodplains with tree planting is 19.8-36.2% for single-stage and 10.4-23.6% for multistage compound channels. The longitudinal dispersion coefficients for each multi-zone model predict a 61% and 41% dispersion reduction, respectively, in single- and multistage floodplains with planted trees. Floodplains with denser tree spacing have a maximum zonal discharge reduction of 45% for a single-stage and 27.2% and 28.0% for multistage channels. These findings strongly suggest that the planting parameters of spacing-to-diameter ratio and floodplain geometry play a pivotal role in floodplain management from the perspective of contaminant dispersion and flood risk reduction during high-flow events.
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Árvores , Florestas , Inundações , Rios , Modelos Teóricos , HidrodinâmicaRESUMO
BACKGROUND: Observational studies have shown that neuroticism is associated with frailty, but the causal relationship between them remains unclear. METHODS: A two-sample Mendelian randomization (MR) study was conducted to explore the bidirectional causal relationship between neuroticism (n = 380,506 for the primary analysis, n = 79,004 for the validation) and frailty (n = 175,226) using publicly available genome-wide association study data. The inverse variance weighted (IVW), weighted median, and MR-Egger were used to obtain the causal estimates. Findings were verified through extensive sensitivity analyses and validated using another dataset. Multivariable MR (MVMR) analysis was performed to estimate the direct causal effects with adjustment of potential confounders. Two-step MR technique was then conducted to explore the mediators in the causal effects of neuroticism on frailty. RESULTS: Genetically-predicted higher neuroticism score was significantly correlated with higher frailty index (IVW beta: 0.53, 95%CI: 0.48 to 0.59, P = 9.3E-83), and genetically-determined higher frailty index was significantly associated with higher neuroticism score (IVW beta: 0.28, 95%CI: 0.21 to 0.35, P = 1.3E-16). These results remained robust across sensitivity analyses and were reproducible using another dataset. The MVMR analysis indicated that the causal relationships remained significant after adjusting for the potential confounding factors. Mediation analysis revealed that depression, years of schooling, and smoking were significantly mediated the causal effects of neuroticism on frailty. CONCLUSIONS: A bidirectional causal relationship existed between neuroticism and frailty. Our findings suggested that early intervention and behavioral changes might be helpful to reduce the neuroticism levels and prevent the development of frailty.
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Fragilidade , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Neuroticismo , Humanos , Fragilidade/genética , Causalidade , Masculino , Feminino , Idoso , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Daptomycin is a last-line antibiotic commonly used to treat vancomycin-resistant Enterococci, but resistance evolves rapidly and further restricts already limited treatment options. While genetic determinants associated with clinical daptomycin resistance (DAPR) have been described, information on factors affecting the speed of DAPR acquisition is limited. The multiple peptide resistance factor (MprF), a phosphatidylglycerol-modifying enzyme involved in cationic antimicrobial resistance, is linked to DAPR in pathogens such as methicillin-resistant Staphylococcus aureus. Since Enterococcus faecalis encodes two paralogs of mprF and clinical DAPR mutations do not map to mprF, we hypothesized that functional redundancy between the paralogs prevents mprF-mediated resistance and masks other evolutionary pathways to DAPR. Here, we performed in vitro evolution to DAPR in mprF mutant background. We discovered that the absence of mprF results in slowed DAPR evolution and is associated with inactivating mutations in ftsH, resulting in the depletion of the chaperone repressor HrcA. We also report that ftsH is essential in the parental, but not in the ΔmprF, strain where FtsH depletion results in growth impairment in the parental strain, a phenotype associated with reduced extracellular acidification and reduced ability for metabolic reduction. This presents FtsH and HrcA as enticing targets for developing anti-resistance strategies.
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Daptomicina , Enterococcus faecalis , Peptídeo Hidrolases , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Daptomicina/farmacologia , Farmacorresistência Bacteriana/genética , Enterococcus faecalis/genética , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/metabolismo , Enterococcus faecalis/enzimologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/metabolismo , Testes de Sensibilidade Microbiana , Mutação , Peptídeo Hidrolases/metabolismo , Peptídeo Hidrolases/genéticaRESUMO
Establishing an immune balance between the mother and fetus during gestation is crucial, with the placenta acting as the epicenter of immune tolerance. The placental transfer of antibodies, mainly immunoglobulin G (IgG), is critical in protecting the developing fetus from infections. This review looks at how immunomodulation of antibody glycosylation occurs during placental transfer and how it affects fetal health. The passage of maternal IgG antibodies through the placental layers, including the syncytiotrophoblast, stroma, and fetal endothelium, is discussed. The effect of IgG subclass, glycosylation, concentration, maternal infections, and antigen specificity on antibody transfer efficiency is investigated. FcRn-mediated IgG transport, influenced by pH-dependent binding, is essential for placental transfer. Additionally, this review delves into the impact of glycosylation patterns on antibody functionality, considering both protective and pathological effects. Factors affecting the transfer of protective antibodies, such as maternal vaccination, are discussed along with reducing harmful antibodies. This in-depth examination of placental antibody transfer and glycosylation provides insights into improving neonatal immunity and mitigating the effects of maternal autoimmune and alloimmune conditions.
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Imunoglobulina G , Placenta , Gravidez , Feminino , Humanos , Placenta/metabolismo , Glicosilação , Trofoblastos/metabolismo , Imunomodulação , Troca Materno-FetalRESUMO
Brown adipose tissue (BAT) exhibits remarkable morphological and functional plasticity in response to environmental (e.g., cold exposure) and nutrient (e.g., high-fat diet) stimuli. Notably, a number of studies have showed that acetate, the main fermentation product of dietary fiber in gut, profoundly influences the differentiation and activity of BAT. However, the potential synergic or antagonistic effects of acetate and cold exposure on BAT have not been well examined. In the present study, the C57BL/6J mice were treated with acetate at the systemic level before a short period of cold exposure. Physiological parameters including body weight, blood glucose, and Respiratory Exchange Ratio (RER) were monitored, and thermal imaging of body surface temperature was captured. Moreover, the transcriptome profiles of interscapular BAT were also determined and analyzed afterwards. The obtained results showed that acetate treatment prior to cold exposure could alter the gene expression profile, as evidenced by significant differential clusters between the two groups. GO analysis and KEGG analysis further identified differentially expressed genes being mainly enriched for a number of biological terms and pathways related to lipid metabolism and brown adipose activity such as "G-protein-coupled receptor activity", "cAMP metabolic process", "PPAR signaling pathway", and "FoxO signaling pathway". GSEA analysis further suggested that activation status of key pathways including "PPAR signaling pathway" and "TCA cycle" were altered upon acetate treatment. Taken together, our study identified the potential synergistic effect of acetic acid with cold exposure on BAT, which highlighted the positive dietary and therapeutic aspects of acetate.
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OBJECTIVE: To explore the brain effect mechanism and the correlation between brain functional imaging and cognitive function in treatment of depressive disorder (DD) with transcutaneous auricular vagus nerve stimulation (taVNS) based on the resting-state functional magenetic reasonance imaging (rs-fMRI). METHODS: Thirty-two DD patients were included in a depression group and 32 subjects of healthy condition were enrolled in a normal group. In the depression group, the taVNS was applied to bilateral Xin (CO15) and Shen (CO10), at disperse-dense wave, 4 Hz/20 Hz in frequency and current intensity ≤20 mA depending on patient's tolerance, 30 min each time, twice daily. The duration of treatment consisted of 8 weeks. The patients of two groups were undertaken rs-fMRI scanning. The scores of Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and Wisconsin card sorting test (WCST) were observed in the normal group at baseline and the depression group before and after treatment separately. The differential brain regions were observed before and after treatment in the two groups and the value of degree centrality (DC) of fMRI was obtained. Their correlation was analyzed in terms of HAMD, HAMA and WCST scores. RESULTS: The scores of HAMD and HAMA in the depression group were all higher than those in the normal group (P<0.05). After treatment, the scores of HAMD and HAMA were lower than those before treatment in the depression group; the scores of total responses, response errors and perseverative errors of WCST were all lower than those before treatment (P<0.05). The brain regions with significant differences included the left inferior temporal gyrus, the left cerebellar peduncles region 1, the left insula, the right putamen, the bilateral supplementary motor area and the right middle frontal gyrus. After treatment, the value of DC in left supplementary motor area was negatively correlated to HAMD and HAMA scores respectively (r=-0.324, P=0.012; r=-0.310, P=0.015); the value of DC in left cerebellar peduncles region 1 was negatively correlated to the total responses of WCST (r=-0.322, P=0.013), and the left insula was positively correlated to the total responses of WCST (r=0.271, P=0.036). CONCLUSION: The taVNS can modulate the intensity of the functional activities of some brain regions so as to relieve depressive symptoms and improve cognitive function.
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Estimulação Elétrica Nervosa Transcutânea , Estimulação do Nervo Vago , Humanos , Depressão/diagnóstico por imagem , Depressão/terapia , Imageamento por Ressonância Magnética/métodos , Estimulação do Nervo Vago/métodos , Encéfalo/diagnóstico por imagem , Estimulação Elétrica Nervosa Transcutânea/métodos , Nervo VagoRESUMO
Purpose: Studies have reported that breast cancer (BC) patients' circulating tumor cells (CTCs) have varying results for their diagnostic role. Thus, we conducted a meta-analysis to systematically assess the accuracy of CTCs in the diagnosis of BC. Methods: A meta-analysis was conducted to evaluate the overall accuracy of CTC detection. A pooled analysis of sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic advantage ratio (DOR) was used to measure diagnostic accuracy. In addition, the area under the summary receiver operating characteristic curve (AUC) was used to discriminate BC from non-BC. An analysis of the threshold effect was calculated using the Spearman correlation coefficient. We calculated the Q and I2 statistics to determine whether the studies were heterogeneous. Sensitivity analysis was performed by removing studies one by one. Publication bias was assessed by Deeks' funnel plot asymmetry test. Results: Studies from the PubMed, Cochrane Library, Embase, Web of Science, Wanfang, Vip, and CNKI databases were collected for diagnosing BC from January 2000 to April March 2023. Finally, 8 publications were retrieved in total containing 2014 cases involved in the study. Based on a random-effects model, it was found that the pooled SEN was 0.69 (0.55 - 0.80), SPE was 0.93 (0.60 - 0.99), PLR was 9.5 (1.4 - 65.9), NLR was 0.33 (0.23 - 0.48), DOR was 29 (4 - 205) and the AUC of the summary receiver operating characteristic (SROC) curve was 0.81 (0.77 - 0.84). Some heterogeneity was found in the article, but there was no threshold effect to account for it (P = 0.27). Deek's funnel plot asymmetry test indicated that no publication bias was observed in this meta-analysis (P = 0.52). Conclusion: The results of this meta-analysis confirmed that CTCs were an important component of noninvasive methods of confirming BC with SEN of 0.69 (0.55 - 0.80), SPE of 0.93 (0.60 - 0.99) and AUC of 0.81 (0.77 - 0.84).
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Activation of heterotrimeric G-proteins (Gαßγ) by G-protein-coupled receptors (GPCRs) is a quintessential mechanism of cell signaling widely targeted by clinically approved drugs. However, it has become evident that heterotrimeric G-proteins can also be activated via GPCR-independent mechanisms that remain untapped as pharmacological targets. GIV/Girdin has emerged as a prototypical non-GPCR activator of G proteins that promotes cancer metastasis. Here, we introduce IGGi-11, a first-in-class small-molecule inhibitor of noncanonical activation of heterotrimeric G-protein signaling. IGGi-11 binding to G-protein α-subunits (Gαi) specifically disrupted their engagement with GIV/Girdin, thereby blocking noncanonical G-protein signaling in tumor cells and inhibiting proinvasive traits of metastatic cancer cells. In contrast, IGGi-11 did not interfere with canonical G-protein signaling mechanisms triggered by GPCRs. By revealing that small molecules can selectively disable noncanonical mechanisms of G-protein activation dysregulated in disease, these findings warrant the exploration of therapeutic modalities in G-protein signaling that go beyond targeting GPCRs.
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Proteínas Heterotriméricas de Ligação ao GTP , Neoplasias , Proteínas de Transporte Vesicular/metabolismo , Proteínas dos Microfilamentos/metabolismo , Transdução de Sinais , Receptores Acoplados a Proteínas G/metabolismo , Proteínas Heterotriméricas de Ligação ao GTP/metabolismo , Neoplasias/metabolismoRESUMO
According to the World Health Organization (https://covid19.who.int/), more than 651 million people have been infected by COVID-19, and more than 6.6 million of them have died. COVID-19 has spread to almost every country in the world because of air travel. Cases of COVID-19 transmission from an index patient to fellow passengers in commercial airplanes have been widely reported. This investigation used computational fluid dynamics (CFD) to simulate airflow and COVID-19 virus (SARS-CoV-2) transport in a variety of airliner cabins. The cabins studied were economy-class with 2-2, 3-3, 2-3-2, and 3-3-3 seat configurations, respectively. The CFD results were validated by using experimental data from a seven-row cabin mockup with a 3-3 seat configuration. This study used the Wells-Riley model to estimate the probability of infection with SARS-CoV-2. The results show that CFD can predict airflow and virus transmission with acceptable accuracy. With an assumed flight time of 4 h, the infection probability was almost the same among the different cabins, except that the 3-3-3 configuration had a lower risk because of its airflow pattern. Flying time was the most important parameter for causing the infection, while cabin type also played a role. Without mask wearing by the passengers and the index patient, the infection probability could be 8% for a 10-h, long-haul flight, such as a twin-aisle air cabin with 3-3-3 seat configuration.
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Activation of heterotrimeric G-proteins (Gαßγ) by G-protein-coupled receptors (GPCRs) is a quintessential mechanism of cell signaling widely targeted by clinically-approved drugs. However, it has become evident that heterotrimeric G-proteins can also be activated via GPCR-independent mechanisms that remain untapped as pharmacological targets. GIV/Girdin has emerged as a prototypical non-GPCR activator of G proteins that promotes cancer metastasis. Here, we introduce IGGi-11, a first-in-class smallmolecule inhibitor of non-canonical activation of heterotrimeric G-protein signaling. IGGi-11 binding to G-protein α-subunits (Gαi) specifically disrupted their engagement with GIV/Girdin, thereby blocking non-canonical G-protein signaling in tumor cells, and inhibiting pro-invasive traits of metastatic cancer cells in vitro and in mice. In contrast, IGGi-11 did not interfere with canonical G-protein signaling mechanisms triggered by GPCRs. By revealing that small molecules can selectively disable non-canonical mechanisms of G-protein activation dysregulated in disease, these findings warrant the exploration of therapeutic modalities in G-protein signaling that go beyond targeting GPCRs.
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BACKGROUND: Previous studies have found that transcutaneous auricular vagus nerve stimulation (taVNS) is clinically effective in the treatment of major depressive disorder (MDD), and its efficacy mechanism is related to modulation of the default mode network (DMN) and cognitive control network (CCN). However, the mechanism of the immediate effect of taVNS for MDD remains to be elucidated. METHODS: A total of 58 patients with MDD and 54 healthy controls(HCs) were included in this study. The MDD group was treated with taVNS for 30 min (20 Hz, 4-6 mA) immediately, and we observed amplitude of low-frequency fluctuations (ALFF) abnormalities in the MDD group and changes in ALFF and functional connectivity (FC) before and after immediate treatment. The ALFF brain regions altered by taVNS induction were used as regions of interest to analyze whole-brain FC changes in the MDD group. RESULTS: After taVNS treatment, ALFF in the right precuneus was decreased in the MDD group. The FC of the right precuneus with the left middle frontal gyrus, the left posterior cingulate gyrus and the left angular gyrus were decreased in the MDD group. Correlation analysis showed that the FC values between the right precuneus and the left posterior cingulate gyrus in the pre-treatment MDD group was negatively correlated with the 17-item Hamilton depression rating scale scores. CONCLUSION: TaVNS has an immediate modulatory effect on DMN and CCN. It would be proposed that these functional networks may be effective targets for the long-term treatment of MDD patients with taVNS.
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Transtorno Depressivo Maior , Estimulação Elétrica Nervosa Transcutânea , Estimulação do Nervo Vago , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/terapia , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Lobo Parietal , Nervo VagoRESUMO
Major depressive disorder is associated with a reward deficit manifested by abnormal striatal function. However, differences between treatment-resistant depression (TRD) and non TRD (nTRD) in striatal whole-brain functional connectivity (FC) have not been elucidated. Thirty-eight patients with TRD, 42 patients with nTRD, and 39 healthy controls (HCs) were recruited for this study. A seed-based FC approach was used to analyze abnormalities in six predefined striatal subregion circuits in the three groups of subjects, and further explore the correlation between abnormal FC and clinical symptoms. Results revealed that compared with the nTRD group, the TRD group showed increased FC of the inferior ventral striatum with the bilateral orbital area of the middle frontal gyrus, right cerebellum posterior lobe, left parahippocampal gyrus, left middle occipital gyrus and left lingual gyrus. Compared with the HC group, the TRD group showed a wider range of altered striatal function than the nTRD group. In the TRD group, the HAMD-17 scores were positively correlated with the FC between the right VRP and the left caudate. This study provides new insights into understanding the specificity of TRD striatal circuits.
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Transtorno Depressivo Maior , Estriado Ventral , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Depressão , Imageamento por Ressonância Magnética , Encéfalo , Estriado Ventral/diagnóstico por imagemRESUMO
Background: Fine particulate matter (PM2.5), one of the major atmospheric pollutants, has a significant impact on human health. However, the determinant power of natural and socioeconomic factors on the spatial-temporal variation of PM2.5 pollution is controversial in China. Methods: In this study, we explored spatial-temporal characteristics and driving factors of PM2.5 through 252 prefecture-level cities in China from 2015 to 2019, based on the spatial autocorrelation and geographically and temporally weighted regression model (GTWR). Results: PM2.5 concentrations showed a significant downward trend, with a decline rate of 3.58 µg m-3 a-1, and a 26.49% decrease in 2019 compared to 2015, Eastern and Central China were the two regions with the highest PM2.5 concentrations. The driving force of socioeconomic factors on PM2.5 concentrations was slightly higher than that of natural factors. Population density had a positive significant driving effect on PM2.5 concentrations, and precipitation was the negative main driving factor. The two main driving factors (population density and precipitation) showed that the driving capability in northern region was stronger than that in southern China. North China and Central China were the regions of largest decline, and the reason for the PM2.5 decline might be the transition from a high environmental pollution-based industrial economy to a resource-clean high-tech economy since the implementation the Air Pollution Prevention and Control Action Plan in 2013. Conclusion: We need to fully consider the coordinated development of population size and local environmental carrying capacity in terms of control of PM2.5 concentrations in the future. This research is helpful for policy-makers to understand the distribution characteristics of PM2.5 emission and put forward effective policy to alleviate haze pollution.
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Pessoal Administrativo , Material Particulado , Humanos , Densidade Demográfica , China , Fatores SocioeconômicosRESUMO
The presence of reward deficits in major depressive disorder is associated with abnormal striatal function. However, differences in striatal whole-brain functional between recurrent depressive episode (RDE) and first-episode depression (FDE) have not been elucidated. Thirty-three patients with RDE, 27 with FDE, and 35 healthy controls (HCs) were recruited for this study. A seed-based functional connectivity (FC) method was used to analyze abnormalities in six predefined striatal subregion circuits among the three groups of subjects and to further explore the correlation between abnormal FC and clinical symptoms. The results revealed that compared with the FDE group, the RDE group showed higher FC of the striatal subregion with the left middle occipital gyrus, left orbital area of the middle frontal gyrus, and bilateral posterior cerebellar gyrus, while showing lower FC of the striatal subregion with the right thalamus, left inferior parietal lobule, left middle cingulate gyrus, right angular gyrus, right cerebellum anterior lobe, and right caudate nucleus. In the RDE group, the HAMD-17 scores were positively correlated with the FC between the left dorsal rostral putamen and the left cerebellum posterior lobe. This study provides new insights into understanding the specificity of striatal circuits in the RDE group.
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To control the transport of particles such as the SARS-CoV-2 virus in airliner cabins, which is a significant concern for the flying public, effective ventilation systems are essential. Validated computational fluid dynamics (CFD) models are frequently and effectively used to investigate air distribution and contaminant transportation. The complex geometry and airflow characteristics in airliner cabins pose a challenge to numerical CFD validation. The objective of this investigation was to identify accurate and affordable validation processes for studying the airflow field and particulate contaminant distribution in airliner cabins during the design process for different ventilation systems. This study quantitatively evaluated the effects of ventilation system, turbulence model, particle simulation method, geometry simplification, and boundary condition assignment on airflow and particulate distributions in airliner cabins with either a mixing ventilation (MV) system or a displacement ventilation (DV) system calculated by CFD. The results showed that among four turbulence models, the standard k-ε, RNG k-ε, realizable k-ε and SST k-ω models, the prediction by the realizable k-ε model agreed most closely with the experimental data. Meanwhile, the steady Eulerian method provided a reasonable prediction of the particle concentration field with low computing cost. The computational domain should be simplified differently for the DV system and the MV system with consideration of the simulation accuracy and computing cost. For more accurate modeling results, the boundary conditions should be assigned in greater detail, taking into account the uniformity on the boundary.
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Ozone and byproducts of ozone-initiated reactions are among the primary pollutants in aircraft cabins. However, investigations of the spatial distribution and reaction mechanisms of these pollutants are insufficient. This study established a computational fluid dynamics-based model to evaluate ozone and byproduct distribution, considering ozone reactions in air, adsorption onto surfaces, and byproduct desorption from surfaces. The model was implemented in an authentic single-aisle aircraft cabin and validated by measurements recorded during the aircraft cruise phase. Ozone concentrations in the supply air-dominated area were approximately 50% higher than that in the passenger breathing zone, suggesting that human surfaces represent a significant ozone sink. The deposition velocity onto human bodies was 21.83 m/h, surpassing 3.97 m/h on other cabin interior surface areas. Our model provides a mechanistic tool to analyze ozone and byproduct concentration distributions, which would be useful for assessing passenger health risks and for developing strategies for healthier aircraft cabin environments.
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Poluição do Ar em Ambientes Fechados , Poluentes Ambientais , Ozônio , Humanos , Ozônio/análise , Poluição do Ar em Ambientes Fechados/análise , Aeronaves , HidrodinâmicaRESUMO
BACKGROUND: MicroRNAs (miRNAs) play pivotal roles in the development and progression of breast cancer (BC). In this study, we attempted to identify miRNAs associated with BC prognosis and progression via integrated analysis. METHODS: We first screened 83 differentially expressed miRNAs (DEMs) in 1249 BC samples and 151 normal samples. We then validated their roles in expression and prognosis of BC, identified two survival-related DEMs, and established a risk model. The prediction efficiency was assessed in both the training and validation groups. Tissue and cell experiments were conducted to verify the regulatory effects of miR-127 in BC. RESULTS: The ROC curve indicated good prediction ability with 1-, 3-, and 5-year survival rates of 0.73, 0.72, and 0.72, respectively. Moreover, hsa-miR-127 was found to be an independent prognostic factor of BC. Functional analyses revealed that it is involved in various cancer pathways such as the PI3K-Akt and p53 pathways. miR-127 expression was down-regulated in both BC tissues and cell lines. The knockdown of miR-127 substantially increased, whereas overexpression decreased BC cell proliferation, invasion, and migration. This effect of miR-127 was consistent with its tumorigenic ability and tumor volume in nude mice. CONCLUSIONS: These findings indicate that low expression of miR-127 contributes to BC migration, invasion, and tumorigenesis and that it can be a therapeutic target and prognostic biomarker for BC.