RESUMO
Background: Major depressive disorder (MDD) is a prevalent and debilitating disorder that has been associated with a range of risk factors and outcomes. Causal pathways between MDD and other traits can be studied using genetic variants as instrumental variables. Methods: A literature review was conducted to identify 201 MDD-associated traits. For 115 traits, there were well-powered genome-wide association study (GWAS) results available that could be used to assess the genetic correlation with MDD. Of these, there were 89 meeting criteria for investigating causal associations in both directions using two-sample Mendelian randomization (TSMR). Of the traits that were not captured by GWAS, 43 could be included as outcomes of MDD using one-sample MR (OSMR). A range of methods and sensitivity tests was applied to gauge robustness of results, together with statistical power analyses to aid interpretation. Outcomes: Moderate to strong genetic overlap was found between MDD and most traits. Support for causal effects of MDD liability were found for circadian, cognitive, diet, medical disease, endocrine, functional, inflammatory, metabolic, mortality, physical activity, reproduction, risk behavior, social, socioeconomic, and suicide outcomes. Most associations were bidirectional, although there was less evidence for diet, disease, and endocrine traits causing MDD risk. Results were robust across sensitivity analyses. Interpretation: This study provides a systematic overview of traits putatively causally related to MDD, confirming previous findings as well as identifying new associations. Our results highlight the importance of MDD as a risk factor cross-cutting across medical, functional, and psychosocial domains and emphasize the need for concerted efforts at reducing this highly prevalent disorder.
RESUMO
PURPOSE: To evaluate the diagnostic performance of Golden-Angle Radial Sparse Parallel (GRASP) MRI in identifying pathological stage T0-1 (ypT0-1) after neoadjuvant chemoradiotherapy (nCRT) in patients with rectal cancer, compared to T2-weighted imaging (T2WI) combined with Diffusion Weighted Imaging (DWI). METHODS: In this retrospective study, 168 patients were carefully selected based on inclusion criteria that targeted individuals with biopsy-confirmed primary rectal adenocarcinoma, identified via MRI as having locally advanced disease (≥ T3 and/or positive lymph node results) prior to nCRT. Post-nCRT, all MRI images obtained after nCRT were assessed by two observers independently. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for identifying ypT0-1 based on GRASP and T2 + DWI were calculated. Multivariable regression analysis was used to explore the factors independently associated with ypT0-1 tumor. RESULTS: 45 patients out of these cases were ypT0-1, and the accuracy, sensitivity, specificity, PPV, and NPV of GRASP were higher than the T2 + DWI (88% vs 74%, 93% vs 71%, 86% vs 75%, 71% vs 52% and 97% vs 88%), the AUC in identifying ypT0-1 tumor based on GRASP was 0.90 (95% CI:0.84, 0.94), which was better than the T2 + DWI (0.73; 95% CI: 0.66, 0.80). Multivariable logistic regression analysis showed that the yT stage on GRASP scans was the only factor independently associated with ypT0-1 tumor (P < 0.001). CONCLUSION: The GRASP helped distinguish ypT0-1 tumor after nCRT and can select patients who may be suitable for local excision.
Assuntos
Imageamento por Ressonância Magnética , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Retais , Sensibilidade e Especificidade , Humanos , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Terapia Neoadjuvante/métodos , Idoso , Imageamento por Ressonância Magnética/métodos , Adulto , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/terapia , Adenocarcinoma/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Quimiorradioterapia/métodosRESUMO
Dog ownership has been associated with several complex traits, and there is evidence of genetic influence. We performed a genome-wide association study of dog ownership through a meta-analysis of 31,566 Swedish twins in 5 discovery cohorts and an additional 65,986 European-ancestry individuals in 3 replication cohorts from Sweden, Norway, and the United Kingdom. Association tests with >7.4 million single-nucleotide polymorphisms were meta-analyzed using a fixed effect model after controlling for population structure and relatedness. We identified 2 suggestive loci using discovery cohorts, which did not reach genome-wide significance after meta-analysis with replication cohorts. Single-nucleotide polymorphism-based heritability of dog ownership using linkage disequilibrium score regression was estimated at 0.123 (CI 0.038-0.207) using the discovery cohorts and 0.018 (CI -0.002 to 0.039) when adding in replication cohorts. Negative genetic correlation with complex traits including type 2 diabetes, depression, neuroticism, and asthma was only found using discovery summary data. Furthermore, we did not identify any genes/gene-sets reaching even a suggestive level of significance. This genome-wide association study does not, by itself, provide clear evidence on common genetic variants that influence dog ownership among European-ancestry individuals.
Assuntos
Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , População Branca , Cães , Animais , Humanos , População Branca/genética , Desequilíbrio de Ligação , Feminino , Masculino , PropriedadeRESUMO
BACKGROUND: Little is known about shared origins between inflammatory bowel disease (IBD) and allergic diseases (asthma, allergic rhinitis, and eczema). We aimed to expand current knowledge on the etiological sources of comorbidities between these disorders using a range of genetically informed methods. METHODS: Within-individual and familial co-aggregation analysis was applied to 2â 873â 445 individuals born in Sweden from 1987 to 2014 and their first- and second-degree relatives. Quantitative genetic modeling was applied to 38â 723 twin pairs to decompose the genetic and environmental sources for comorbidity. Polygenic risk score analysis between IBD and allergic diseases was conducted in 48â 186 genotyped twins, and linkage disequilibrium score regression was applied using publicly available data to explore the genetic overlap. RESULTS: IBD was associated with asthma (adjusted odds ratio [aOR], 1.35; 95% confidence interval [CI], 1.30 to 1.40), allergic rhinitis (aOR, 1.27; 95% CI, 1.20 to 1.34), and eczema (aOR, 1.47; 95% CI, 1.38 to 1.56), with similar estimates for ulcerative colitis or Crohn's disease. The ORs for familial co-aggregation decreased with decreasing genetic relatedness. Quantitative genetic modeling revealed little evidence of common genetic factors between IBD and allergic diseases (eg, IBD and allergic rhinitis; genetic correlation raâ =â 0.06; 95% CI, -0.03 to 0.15) but did reveal some evidence of unique environmental factors between IBD and eczema (reâ =â 0.16; 95% CI, 0.00 to 0.32). Molecular genetic analyses were similarly null for IBD and allergic diseases, except for a slight association between Crohn's disease polygenic risk score and eczema (OR, 1.09; 95% CI, 1.06 to 1.12). CONCLUSIONS: We found little evidence to support a shared origin between IBD and any allergic disease but weak evidence for shared genetic and unique environmental components for IBD and eczema.
Comorbidities between inflammatory bowel disease (IBD) with asthma and allergic diseases have been documented, but shared origin remains unknown. Using multiple genetically informed approaches, we found little evidence of a shared origin explaining the comorbidities of IBD with asthma and allergic rhinitis but weak evidence for IBD and eczema.
RESUMO
BACKGROUND: Maternal psychological stress during pregnancy and postnatally has been shown to be associated with offspring atopic diseases (asthma, atopic dermatitis and allergic rhinitis). The aim of this study was to assess whether this association may be attributable to the child's own mental health disorders. METHOD: The study population included 15,092 twin children born 2002-2010 in Sweden. Questionnaire data at age 9 years was linked to national patient- and prescription registers. Maternal mental health during pregnancy and 3 years postnatally were identified from diagnosis and medication data (depression, anxiety and stress disorders). Atopic diseases in children were identified from questionnaires, diagnosis and medication data. Child mental health status (depression and anxiety) was identified from questionnaires. Three-way decomposition methods tested for mediation or interaction by child mental health disorders. RESULTS: Maternal mental health disorders were associated with most child atopic diseases including asthma aRR1.36 (95% CI 1.12, 1.60), and child mental health disorders, aRR1.73 (95% CI 1.56, 1.92). Children with mental health disorders were comorbid for atopic diseases with only asthma reaching statistical significance, aRR1.29 (95% CI 1.14, 1.47). Three-way decomposition found that mediation or interaction by child mental health disorders did not account for the mother mental health and child atopy associations except in parent-report asthma, where child mental health disorders mediated 13.4% (95% CI 2.1, 24.7) of the effect, but not for objectively defined (diagnosis and medication) asthma. CONCLUSION: The associations between maternal mental health and child asthma and allergic diseases do not appear to be attributable to child mental health disorders.
Assuntos
Asma , Dermatite Atópica , Rinite Alérgica , Criança , Feminino , Gravidez , Humanos , Saúde Mental , Asma/epidemiologia , Dermatite Atópica/epidemiologia , Rinite Alérgica/epidemiologia , MãesRESUMO
BACKGROUND: To compare the diagnostic performance of Lung-RADS (lung imaging-reporting and data system) 2022 and PNI-GARS (pulmonary node imaging-grading and reporting system). METHODS: Pulmonary nodules (PNs) were selected at four centers, namely, CQ Center (January 1, 2018-December 31, 2021), HB Center (January 1, 2021-June 30, 2022), SC Center (September 1, 2021-December 31, 2021), and SX Center (January 1, 2021-December 31, 2021). PNs were divided into solid nodules (SNs), partial solid nodules (PSNs) and ground-glass nodules (GGNs), and they were then classified by the Lung-RADS and PNI-GARS. The sensitivity, specificity and agreement rate were compared between the two systems by the χ2 test. RESULTS: For SN and PSN, the sensitivity of PNI-GARS and Lung-RADS was close (SN 99.8% vs. 99.4%, P < 0.001; PSN 99.9% vs. 98.4%, P = 0.015), but the specificity (SN 51.2% > 35.1%, PSN 13.3% > 5.7%, all P < 0.001) and agreement rate (SN 81.1% > 74.5%, P < 0.001, PSN 94.6% > 92.7%, all P < 0.05) of PNI-GARS were superior to those of Lung-RADS. For GGN, the sensitivity (96.5%) and agreement rate (88.6%) of PNI-GARS were better than those of Lung-RADS (0, 18.5%, P < 0.001). For the whole sample, the sensitivity (98.5%) and agreement rate (87.0%) of PNI-GARS were better than Lung-RADS (57.5%, 56.5%, all P < 0.001), whereas the specificity was slightly lower (49.8% < 53.4%, P = 0.003). CONCLUSION: PNI-GARS was superior to Lung-RADS in diagnostic performance, especially for GGN.
Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , ChinaRESUMO
Maternal educational attainment (MEA) shapes offspring health through multiple potential pathways. Differential DNA methylation may provide a mechanistic understanding of these long-term associations. We aimed to quantify the associations of MEA with offspring DNA methylation levels at birth, in childhood and in adolescence. Using 37 studies from high-income countries, we performed meta-analysis of epigenome-wide association studies (EWAS) to quantify the associations of completed years of MEA at the time of pregnancy with offspring DNA methylation levels at birth (n = 9 881), in childhood (n = 2 017), and adolescence (n = 2 740), adjusting for relevant covariates. MEA was found to be associated with DNA methylation at 473 cytosine-phosphate-guanine sites at birth, one in childhood, and four in adolescence. We observed enrichment for findings from previous EWAS on maternal folate, vitamin-B12 concentrations, maternal smoking, and pre-pregnancy BMI. The associations were directionally consistent with MEA being inversely associated with behaviours including smoking and BMI. Our findings form a bridge between socio-economic factors and biology and highlight potential pathways underlying effects of maternal education. The results broaden our understanding of bio-social associations linked to differential DNA methylation in multiple early stages of life. The data generated also offers an important resource to help a more precise understanding of the social determinants of health.
RESUMO
In order to reveal the community characteristics and trophic structure of oribatid mites in different moss habitats in karst caves, the oribatid mites in the moss habitats of ground (GD), understory (US), cave wall (CW), surface shrub (SB) and farmland (FL) outside the cave were collected in October 2021. Through the identification and data analysis of oribatid mites, 2352 oribatid mites were found, belonging to 45 families and 72 genera, most of which were Gymnonota. The family number, genus number, individual number, individual density, dominant genus composition, community diversity, community similarity, MGP (Analysis methods for ecological groups of oribatid mites) ecological group of oribatid mites and trophic structure of oribatid mites in different moss were analyzed. The results showed that: (1) The number of families, genera, individuals, and individual density of SB and FL are higher than those of the other three habitats; (2) Platyliodes, Oppiella, Tectocepheus, Scutovertex, Scheloribates and Trichogalumna are the dominant genera of the oribatid mites in the cave moss habitat, among them, Tectocepheus and Trichogaluna have the most obvious advantages; (3) The diversity index of shrub (SB) was higher than that of other four habitats; Similarity between ground and cave wall, shrub and farmland is high; (4) The MGP ecological group of oribatid mites in different habitats is dominated by O type (Overall type belongs to MGP analysis results, 20%≤M,G,P≤50%), and a total of 42 genera of oribatid mites preliminarily constitute the trophic structure of oribatid mites in the cave moss habitat. Based on the above results, it can be concluded that there are differences in the community structure of oribatid mites in different moss habitats in the study area, and the use of dominant genera of mites can preliminarily indicate the environmental conditions of different moss habitats. This study enriches the study of mites in karst cave mosses, and can provide theoretical significance for the protection of cave biodiversity in karst areas.
Assuntos
Briófitas , Ácaros , Humanos , Animais , Cavernas , Biodiversidade , Análise de DadosRESUMO
INTRODUCTION: Cancer mortality worldwide highlights the urgency for advanced therapeutic methods to fill the gaps in conventional cancer therapies. Bacteriotherapy is showing great potential in tumor regression due to the motility and colonization tendencies of bacteria. However, the complicated in vivo environment and tumor pathogenesis hamper the therapeutic outcomes. Synthetic engineering methods endow bacteria with flexible abilities both at the extracellular and intracellular levels to meet treatment requirements. In this review, we introduce synthetic engineering methods for bacterial modifications. We highlight the recent progress in engineered bacteria and explore how these synthetic methods endow bacteria with superior abilities in cancer therapy. The current clinical translations are further discussed. Overall, this review may shed light on the advancement of engineered bacteria for cancer therapy. AREAS COVERED: Recent progress in synthetic methods for bacterial engineering and specific examples of their applications in cancer therapy are discussed in this review. EXPERT OPINION: Bacteriotherapy bridges the gaps of conventional cancer therapies through the natural motility and colonization tendency of bacteria, as well as their synthetic engineering. Nevertheless, to fulfill the bacteriotherapy potential and move into clinical trials, more research focusing on its safety concerns should be conducted.
Assuntos
Bactérias , Neoplasias , Humanos , Bactérias/genética , Neoplasias/terapiaRESUMO
PURPOSE: To investigate the feasibility of high-resolution readout-segmented echo-planar imaging (rs-EPI) with simultaneous multislice (SMS) imaging to predict well-differentiated rectal cancer.Kindly check and confirm whether the Author Name 'Hongyun Huang ' is correctly identified.confirm METHODS: A total of eighty-three patients with nonmucinous rectal adenocarcinoma received both prototype SMS high-spatial-resolution and conventional rs-EPI sequences. Image quality was subjectively assessed by two experienced radiologists using a 4-point Likert scale (1 = poor, 4 = excellent). The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) and apparent diffusion coefficient (ADC) of the lesion were measured by two experienced radiologists in the objective assessment. Paired t tests or MannâWhitney U tests were used to compare the two groups. The areas under the receiver operating characteristic (ROC) curves (AUCs) were used to determine the predictive value of the ADCs in discriminating well-differentiated rectal cancer in the two groups. A two-sided p value < 0.05 represented statistical significance.Please check and confirm if the authors and affiliation details have been correctly identified. Amend if necessary.confirm RESULTS: In the subjective assessment, high-resolution rs-EPI had better image quality than conventional rs-EPI (p < 0.001). High-resolution rs-EPI also had a significantly higher SNR and CNR (p < 0.001). The T stage of rectal cancer was inversely correlated with the ADCs measured on high-resolution rs-EPI (r = -0.622, p < 0.001) and rs-EPI (r = -0.567, p < 0.001). The AUC of high-resolution rs-EPI in predicting well-differentiated rectal cancer was 0.768. CONCLUSION: High-resolution rs-EPI with SMS imaging provided significantly higher image quality, SNRs, and CNRs and more stable ADC measurements than conventional rs-EPI. Additionally, the pretreatment ADC on high-resolution rs-EPI could discriminate well-differentiated rectal cancer.
Assuntos
Imagem Ecoplanar , Neoplasias Retais , Humanos , Imagem Ecoplanar/métodos , Estudos de Viabilidade , Reprodutibilidade dos Testes , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Retais/diagnóstico por imagemRESUMO
INTRODUCTION: To investigate the association between maternal depression/anxiety during pregnancy and offspring type 1 diabetes, to assess the specific importance of exposure during pregnancy by comparing across different exposure periods before and/or after pregnancy, and to explore potential unmeasured familial confounding. RESEARCH DESIGN AND METHODS: This was a population-based cohort including 1 807 809 offspring born in Sweden 2002-2019. From national registers, data were available on diagnosis or medication prescription for depression/anxiety in and around pregnancy, as well as incident cases of type 1 diabetes defined through diagnosis or insulin treatment. Associations were examined using flexible parametric and Cox regression models. Familial confounding was explored using paternal exposure as a negative control and by comparing offspring exposed to maternal depression/anxiety with their unexposed siblings. RESULTS: For exposure during pregnancy, maternal depression/anxiety was associated with an increased risk of offspring type 1 diabetes onset after, but not before, 8 years of age (adjusted HR (aHR) 1.21 (95% CI 1.03 to 1.42]). Exposure occurring only during pregnancy was similarly associated to type 1 diabetes (aHR 1.24 (0.96 to 1.60)), whereas exposure occurring only before pregnancy was not (aHR 0.91 (0.64 to 1.30)). Associations were close to the null for paternal depression/anxiety (aHR 0.95 (0.72 to 1.25)), and point estimates were above 1 in sibling comparisons, although with wide CIs (aHR 1.36 (0.82 to 2.26)). CONCLUSIONS: Maternal depression/anxiety specifically during pregnancy seems to be associated with offspring type 1 diabetes. Paternal negative control and sibling comparisons indicate that the results cannot entirely be explained by familial confounding.
Assuntos
Diabetes Mellitus Tipo 1 , Efeitos Tardios da Exposição Pré-Natal , Masculino , Feminino , Humanos , Estudos de Coortes , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/complicações , Depressão/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Ansiedade/epidemiologiaRESUMO
PURPOSE: To build computed tomography enterography (CTE)-based multiregional radiomics model for distinguishing Crohn's disease (CD) from intestinal tuberculosis (ITB). MATERIALS AND METHODS: A total of 105 patients with CD and ITB who underwent CTE were retrospectively enrolled. Volume of interest segmentation were performed on CTE and radiomic features were obtained separately from the intestinal wall of lesion, the largest lymph node (LN), and region surrounding the lesion in the ileocecal region. The most valuable radiomic features was selected by the selection operator and least absolute shrinkage. We established nomogram combining clinical factors, endoscopy results, CTE features, and radiomic score through multivariate logistic regression analysis. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the prediction performance. DeLong test was applied to compare the performance of the models. RESULTS: The clinical-radiomic combined model comprised of four variables including one radiomic signature from intestinal wall, one radiomic signature from LN, involved bowel segments on CTE, and longitudinal ulcer on endoscopy. The combined model showed good diagnostic performance with an area under the ROC curve (AUC) of 0.975 (95% CI 0.953-0.998) in the training cohort and 0.958 (95% CI 0.925-0.991) in the validation cohort. The combined model showed higher AUC than that of the clinical model in cross-validation set (0.958 vs. 0.878, P = 0.004). The DCA showed the highest benefit for the combined model. CONCLUSION: Clinical-radiomic combined model constructed by combining CTE-based radiomics from the intestinal wall of lesion and LN, endoscopy results, and CTE features can accurately distinguish CD from ITB.
Assuntos
Doença de Crohn , Tuberculose dos Linfonodos , Humanos , Doença de Crohn/patologia , Estudos Retrospectivos , Diagnóstico Diferencial , Tomografia Computadorizada por Raios X/métodosRESUMO
Aging is classically conceptualized as an ever-increasing trajectory of damage accumulation and loss of function, leading to increases in morbidity and mortality. However, recent in vitro studies have raised the possibility of age reversal. Here, we report that biological age is fluid and exhibits rapid changes in both directions. At epigenetic, transcriptomic, and metabolomic levels, we find that the biological age of young mice is increased by heterochronic parabiosis and restored following surgical detachment. We also identify transient changes in biological age during major surgery, pregnancy, and severe COVID-19 in humans and/or mice. Together, these data show that biological age undergoes a rapid increase in response to diverse forms of stress, which is reversed following recovery from stress. Our study uncovers a new layer of aging dynamics that should be considered in future studies. The elevation of biological age by stress may be a quantifiable and actionable target for future interventions.
Assuntos
COVID-19 , Humanos , Animais , Camundongos , Envelhecimento/fisiologia , ParabioseRESUMO
OBJECTIVES: To investigate the feasibility of high-resolution integrated dynamic shimming echo planar imaging (iEPI) applied to rectal cancer. METHODS: A total of seventy-eight patients with non-mucinous rectum adenocarcinoma were enrolled in this study. Using a prototype high-resolution iEPI sequence, high-resolution single-shot EPI (sEPI) sequence, and sEPI sequence, subjective and objective assessment and apparent diffusion coefficient (ADC) value were measured for comparison. The spearman rank correlation analysis test and the receiver operating characteristic curve were performed to evaluate correlation between tumor ADC values, corresponding T stage, and differentiation degree of rectal cancer. RESULTS: The subjective assessment of the image quality (IQ) of high-resolution iEPI was rated superior to high-resolution sEPI and sEPI by both readers (p < 0.001). Signal-to-noise ratio, contrast-to-noise, and signal-intensity ratio were significantly higher in high-resolution iEPI than the other two sequences (p < 0.001). There was no significant difference of tumor ADC values among three EPI sequences in the group of low- to well-differentiated rectal cancer. An inverse correlation was noted between ADC values on three DWI sequences and pathological T stage of rectal cancer (r = - 0.693, - 0.689, - 0.640, p < 0.001). The AUC values of high-resolution iEPI, high-resolution sEPI, and sEPI in predicting well-differentiated rectal cancer were 0.910, 0.761, and 0.725 respectively. CONCLUSIONS: In conclusion, the high-resolution iEPI provided significantly higher IQ and stable ADC compared to another two sequences. High-resolution iEPI has the highest efficacy among three examined sequences in differentiation of rectal cancer with different degrees of differentiation. KEY POINTS: ⢠High-resolution iEPI provided a significantly better IQ than high-resolution sEPI and sEPI when assessing rectal cancer. ⢠The AUC of high-resolution sEPI was the highest among three EPI sequences in predicting well-differentiated rectal cancer.
Assuntos
Imagem de Difusão por Ressonância Magnética , Neoplasias Retais , Humanos , Imagem de Difusão por Ressonância Magnética/métodos , Razão Sinal-Ruído , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Imagem Ecoplanar/métodos , Reto/patologia , Reprodutibilidade dos TestesRESUMO
Thrombosis is a major contributor to global disease burden. Antiplatelet therapy is the critical approach to prevent thrombosis by reducing platelet reactivity. However, classical antiplatelet strategies generally interfere with platelet integrin αIIbß3-mediated platelet activation, thereby facing severe bleeding risk. To break the limitation, we described an integrin αIIbß3-independent antiplatelet method by cytosolic delivery of nanoscale perfluorocarbon (PFC) to platelets via albumin carrier. Denatured albumin was found to build high affinity with platelets to mediate cytosolic PFC delivery. While, cytosolic PFC impaired cytoskeleton reorganization during platelet activation to inhibit relevant platelet functions, but avoided to interfere with integrin αIIbß3. We proved that this αIIbß3-indenpendent antiplatelet pattern showed potential antiplatelet effect with low bleeding risk to prevent thrombosis in various thrombosis models. Together, cytosolic PFC delivery via albumin is a promising antiplatelet approach, and will provide an alternative regimen for current antithrombotic therapy.
Assuntos
Plaquetas , Trombose , Humanos , Fibrinolíticos/uso terapêutico , Trombose/tratamento farmacológico , Trombose/prevenção & controle , Albuminas , Integrinas , Agregação PlaquetáriaRESUMO
BACKGROUND: There is some evidence that autism spectrum disorder (ASD) frequently co-occurs with immune-mediated conditions including asthma. We aimed to explore the familial co-aggregation of ASD and asthma using different genetically informed designs. METHODS: We first examined familial co-aggregation of asthma and ASD in individuals born in Sweden from 1992 to 2007 (n = 1 569 944), including their full- and half-siblings (n = 1 704 388 and 356 544 pairs) and full cousins (n = 3 921 890 pairs), identified using Swedish register data. We then applied quantitative genetic modeling to siblings (n = 620 994 pairs) and twins who participated in the Child and Adolescent Twin Study in Sweden (n = 15 963 pairs) to estimate the contribution of genetic and environmental factors to the co-aggregation. Finally, we estimated genetic correlations between traits using linkage disequilibrium score regression (LDSC). RESULTS: We observed a within-individual association [adjusted odds ratio (OR) 1.33, 95% confidence interval (CI) 1.28-1.37] and familial co-aggregation between asthma and ASD, and the magnitude of the associations decreased as the degree of relatedness decreased (full-siblings: OR 1.44, 95% CI 1.38-1.50, maternal half-siblings: OR 1.28, 95% CI 1.18-1.39, paternal half-siblings: OR 1.05, 95% CI 0.96-1.15, full cousins: OR 1.06, 95% CI 1.03-1.09), suggesting shared familial liability. Quantitative genetic models estimated statistically significant genetic correlations between ASD traits and asthma. Using the LDSC approach, we did not find statistically significant genetic correlations between asthma and ASD (coefficients between -0.09 and 0.12). CONCLUSIONS: Using different genetically informed designs, we found some evidence of familial co-aggregation between asthma and ASD, suggesting the weak association between these disorders was influenced by shared genetics.
Assuntos
Asma , Transtorno do Espectro Autista , Criança , Adolescente , Humanos , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/genética , Predisposição Genética para Doença , Família , Irmãos , Asma/epidemiologia , Asma/genética , Suécia/epidemiologiaRESUMO
Background and aims: To investigate the effect of short-term very-low-calorie restriction (VLCR) on metabolism in patients with type 2 diabetes (T2D), and elucidate the molecular mechanism through analyses on gut microbiota and small-molecule metabolites. Methods: Fourteen T2D patients were hospitalized to receive VLCR (300-600 kcal/d) for 9 days. BMI, BP, and HR were taken before and after VLCR. Levels of blood lipids, fasting insulin, FBG, and 2h PBG were assessed. The microbial diversity in feces was detected by 16S rDNA high-throughput sequencing technology, and small-molecule metabolites in plasma and feces by untargeted metabolomics technology. Results: After VLCR, BW, BMI, WC, BP, and levels of FBG and 2h PBG, insulin, HOMA-IR, and triglyceride decreased significantly in T2D patients (P<0.05). There was no significant change in the α-diversity of fecal microbiota, but the abundance of Bacteroidetes increased significantly, and the Firmicutes/Bacteroidetes ratio decreased significantly from 11.79 to 4.20. Parabacteroides distasonis showed an abundance having increased most prominently after VLCR treatment. Plasma level of amino acid metabolite L-arginine increased significantly. Plasma levels of three lipid metabolites, PC (14:0/20:4 [8Z, 11Z, 14Z, 17Z]), LysoPC (16:1 [9Z]) and LysoPC (18:1 [11Z]), were significantly reduced. Fecal levels of lipid metabolite LysoPC (18:1 [11Z]) and bile acid metabolite glycholic acid were significantly decreased. Conclusion: In T2DM patients, VLCR can considerably reduce body weight and improve glucose and lipid metabolism without causing severe side effects. LysoPC (18:1 [11Z]) and Parabacteroides distasonis showed the most obvious difference after VLCR, which could be the indicators for VLCR in T2D.
Assuntos
Bacteroidetes , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Humanos , Restrição Calórica , Insulina , LipídeosRESUMO
Bone marrow is one of the most important organs in the human body. The evaluation of bone marrow microstructure and gender-related cellular and capillary networks in healthy young adults can help to better understand the process of bone metabolism. Intravoxel incoherent motion (IVIM) provides both diffusion and perfusion quantifications without requiring intravenous contrast agent injection. In this prospective study, 60 healthy young age-matched volunteers (30 men and 30 women) underwent MRI scans at 1.5 T using multi-b-value diffusion-weighted imaging on sagittal planes covering the lumbar bone marrow. The apparent diffusion coefficient (ADC), true ADC (D), pseudo-ADC (D*), and perfusion fraction (f) were calculated from the diffusion-weighted images using the mono- and bi-exponential models. Lumbar cancellous bone (L2-L4) was selected as the region of interest. An independent t-test was used to detect significant differences in ADC values and IVIM parameters between men and women. The differences in IVIM parameters among the L2, L3, and L4 groups were compared with analysis of variance. The D and f values in women were significantly higher than that in men (p = 0.001, 0.026). However, D* was significantly lower in women than that in men (p = 0.001). Furthermore, there was no significant gender difference for the conventional ADC value (p = 0.186). Moreover, there were no significant differences in the D, f, and D* values among the L2, L3, and L4 vertebras of women or men. IVIM parameters can show differences in bone marrow between young women and men. As a non-invasive method, it can assess bone marrow microstructure, such as cellularity and perfusion.
Assuntos
Medula Óssea , Imagem de Difusão por Ressonância Magnética , Masculino , Feminino , Humanos , Adulto Jovem , Medula Óssea/diagnóstico por imagem , Estudos Prospectivos , Nível de Saúde , Osso EsponjosoRESUMO
Objective: A case-control study explored the application of case-based teaching methods in the clinical teaching of radiology. Materials and Methods: 126 radiology interns of grade 2018 were selected by cluster sampling and randomly divided into the research group and the control group. The traditional teaching approach was used in the control group and the primary teaching principle was used in the research group. The teaching effects of the two groups were compared. Results: The interns' test scores, the research group's case summary multiple-choice questions, case-group multiple-choice questions, case analysis questions, theoretical total scores, and practical operation assessment scores were significantly higher than those of the control group, and the difference was statistically significant (P < 0.05). The total score of dimensions of the interns' critical thinking ability in the study group were significantly higher than those in the control group, and the difference was statistically significant (P < 0.05). The interns' perception of teachers, students' academic self-perception, students' perception of environment, students' social self-perception, and the total score of the DREEM scale in the study group were considerably greater than those in the control group, and the difference was statistically significant (P < 0.05). After teaching, the scores of systematic thinking ability and evidence-based thinking ability of the interns were significantly increased. The improvement in the study group was more significant than that in the control group, and the difference was statistically significant (P < 0.05). Following teaching, the scores of learning interest, self-management, plan implementation, and mutual cooperation of the interns in the two groups were significantly upregulated, and the difference was statistically significant (P < 0.05). Among them, the improvement of interns' abilities in the research group was significantly better than that in the control group, and the difference was statistically significant (P < 0.05). The scores of learning goal, learning process, learning effect, classroom environment construction, teaching strategy, and technology application in the research group were greater than those in the control group, and the difference was statistically significant (P < 0.05). The satisfaction rate of the study group was higher than that of the control group, and the difference was statistically significant (P < 0.05). Conclusion: The application of the case teaching method based on primary teaching principle in the radiology clinical teaching course is helpful to cultivate students' critical thinking ability and improve students' performance and classroom teaching effectiveness.
Assuntos
Radiologia , Estudos de Casos e Controles , Humanos , Aprendizagem , Estudantes , EnsinoRESUMO
Objective: To study the application value of PBL (Problem-Based Learning) combined with a situational simulation teaching method in clinical practice teaching of radiology. Methods: 120 interns who practiced in the radiology department of our hospital from 2020 to 2021 were randomly divided into a study group and a control group. The research group used PBL combined with the scenario simulation teaching method to carry out clinical practice teaching activities. The control group was carried out according to the conventional teaching plan. After 3 months, the teaching effect and satisfaction of the two groups were compared. Results: The imaging report quality control score, intravenous contrast agent score, and practice test score in the study group were higher than those in the control group. The scores of the small class and special class in the research group were higher than those in the control group, and the difference was statistically significant (P < 0.05). The scores of job competency questionnaire in the research group were higher than those in the control group (P < 0.05). The occupational self-efficacy questionnaire score of the research group was higher than that of the control group (P < 0.05). The nursing practice satisfaction score of the research group was higher than that of the control group (P < 0.05). Conclusion: The value of PBL combined with the scenario simulation teaching method in the teaching of radiology clinical practice is significant, which can improve the work ability of interns and make them more satisfied.