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1.
Front Oncol ; 12: 904625, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35912203

RESUMO

Background: To evaluate and compare the potential performance of various diffusion parameters obtained from mono-exponential model (MEM)-, bi-exponential model (BEM)-, and stretched exponential model (SEM)-based diffusion-weighted imaging (DWI) in grading of esophageal squamous carcinoma (ESC). Methods: Eighty-two patients with pathologically confirmed ESC without treatment underwent multi-b-value DWI scan with 13 b values (0~12,00 s/mm2). The apparent diffusion coefficient (ADC) deriving from the MEM; the pure molecular diffusion (ADCslow), pseudo-diffusion coefficient (ADCfast), perfusion, and fraction (f) deriving from the BEM; and the distributed diffusion coefficient (DDC) and water molecular diffusion heterogeneity index (α) deriving from the SEM were calculated and compared between poorly differentiated and well/moderately differentiated ESC, respectively. The prediction parameters and diagnostic efficiency were compared by drawing receiver operating characteristic (ROC) curves. Results: The ADC, ADCslow, ADCfast, and DDC in poorly ESC were significantly lower than those in well/moderately differentiated ones. By using only one parameter, ADCslow, DDC had the moderate diagnostic efficiency and the areas under the curve (AUC) were 0.758 and 0.813 in differentiating ESC. The DDC had the maximum AUC with sensitivity (88.00%) and specificity (68.42%). Combining ADC with ADCfast, ADCslow, and DDC and combining ADCslow with ADCfast can provide a higher diagnostic accuracy with AUC ranging from 0.756, 0.771, 0.816, and 0.793, respectively. Conclusion: Various parameters derived from different DWI models including MEM, BEM, and SEM were potentially helpful in grading ESC. DDC obtained from SEM was the most promising diffusion parameter for predicting the grade of ESC.

2.
EClinicalMedicine ; 52: 101594, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35923428

RESUMO

Background: Optimal uptake rates of low-dose computed tomography (LDCT) scans are essential for lung cancer screening (LCS) to confer mortality benefits. We aimed to outline the process model of the LCS programme in China, identify the high-risk individuals with low uptake based on a prospective multi-centre population-based cohort, and further explore associated structural characteristics. Methods: A total of 221,955 individuals at high-risk for lung cancer from the National Lung Cancer Screening cohort were included. The logistic regression model was performed to identify the individual characteristics associated with the uptake of LCS, defined as whether the high-risk individual undertook LDCT scans in designated hospitals within six months following the initial risk assessment. The linear regression model was adopted to explore the structural characteristics associated with the uptake rates in 186 communities. Findings: The overall uptake rate was 33·0%. The uptake rate was negatively correlated with the incidence of advanced-stage lung cancer (Pearson's coefficient -0·88, p-value 0·0007). Multivariable regression models found that lower uptake rates were associated with males (OR 0·88, 95%CI 0·85-0·91), current smokers (OR 0·93, 95%CI 0·90-0·96), individuals with depressive symptoms (OR 0·92, 95%CI 0·90-0·94), and the structural characteristics, including longer structural delays in initiating LDCT scans (30-90 days vs. ≤14 days: ß -7·17, 95%CI -12·76∼ -1·57; >90 days vs. ≤14 days: ß -13·69, 95%CI -24·61∼ -2·76), no media-assisted publicity (ß -6·43, 95%CI -11·26∼ -1·60), and no navigation assistance (ß -5·48, 95%CI -10·52∼ -0·44). Interpretation: Multifaceted interventions are recommended, which focus on poor-uptake individuals and integrate the 'assessment-to-timely-screening' approach to minimise structural delays, media publicity, and a navigation assistance along the centralised screening pathway. Funding: Ministry of Finance and National Health Commission of the People's Republic of China.

3.
Mitochondrial DNA B Resour ; 7(7): 1389-1391, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35923639

RESUMO

Acer miaotaiense P. C. Tsoong is a rare and endangered tree endemic to the Qinling Mountains of China and is listed as a national third-class protected plant. In this study, we sequenced the complete mitochondrial genome of Acer miaotaiense using the Illumina Novaseq 6000 and Nanopore platforms. The total mitochondrial genome length is 819,227 bp and has 69 genes, including 41 protein-coding, 25 tRNA, and 3 rRNA genes. The genome nucleotide composition was asymmetric, with an overall G + C content of 45.7%. Phylogenetic analysis indicated that Acer miaotaiense is closely related to the congeneric Acer yangbiense.

4.
Int J Surg ; : 106788, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35931353

RESUMO

BACKGROUND: Multiple studies and meta-analyses have reported the diagnostic value of C-reactive protein (CRP) in several diseases. However, the precision, and influence of potential bias regarding the diagnostic values of existing evidence may have implications for clinical practice. METHODS: We performed an umbrella review of diagnostic test accuracy studies of CRP for diseases by searching PubMed, Embase, China National Knowledge Infrastructure, and WanFang databases up to March 7, 2021. Five independent reviewers evaluated eligibility, extracted data, and assessed methodological quality. We descriptively analyzed the diagnostic accuracy of CRP for multiple diseases, heterogeneity between studies, and publication bias. RESULTS: Seventy-four meta-analyses were included, with 13 diseases classified according to the International Classification of Diseases-11 (ICD-11). The methodological quality of the included meta-analyses was mostly low, with only 16 meta-analyses rated as moderate or high, including seven diseases classified by ICD-11. CRP had a relatively greater diagnostic accuracy for two of these diseases. For postoperative infectious complications after bariatric surgery, sensitivity and specificity were 0.81 (0.34-1) and 0.91 (0.73-1), respectively. For anastomotic leakage after colorectal surgery, sensitivity and specificity were 0.95 (0.75-0.99) and 0.95 (0.75-0.99), respectively. CONCLUSIONS: The diagnostic accuracy of CRP for multiple diseases has been extensively studied; however, most studies have low methodological quality. Evidence indicates that CRP has a relatively greater diagnostic accuracy for inflammation and infection diseases, especially for postoperative infectious complications after bariatric surgery and anastomotic leakage after colorectal surgery.

5.
Artigo em Inglês | MEDLINE | ID: mdl-35925460

RESUMO

This study aimed to find an effective, inexpensive, and safe washing treatment for municipal solid waste incineration bottom ash (MSWIBA) in order to reduce its potential harmful effects in disposal and recycling. The washing solutions, namely tap water (TW), saturated lime water (SLW), and wastewater from concrete batching plant (WW) were used to wash MSWIBA at different liquid-solid (L/S) ratios and for different durations. Leaching behavior of some heavy metals, chloride, and sulfate from MSWIBA was tested and evaluated. From the TCLP leaching test, when the L/S ratio was above 5, WW was the most effective solution in reducing As, Cd, Se, and Sb emissions from MSWIBA. The calcium and iron ions present in the WW were essential for controlling the leaching of As, Cd, and Sb from MSWIBA due to the formation of stable crystalline pharmacosiderite, cadmium hydroxide sulfate, and hydromeite during the washing process. Using WW showed the best effect in removing sulfate from MSWIBA. At a L/S ratio of 10, about 83% of the sulfate could be removed from MSWIBA after 20 min of washing. The L/S ratio was most influential in removing chloride from MSWIBA. The three washing treatments chosen were effective in reducing the chloride level in MSWIBA to below the level of hazardous waste. Nevertheless, there were still substantial amounts of chloride remaining in the treated MSWIBA. Under the Dutch Building Materials Decree, the treated MSWIBA may be used as a building material in parts which allow isolation, control, and monitoring (ICM).

6.
Head Neck ; 44(9): 2055-2062, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35915861

RESUMO

BACKGROUND: Parotid lymphoepithelial carcinoma (LEC) is a rare malignant tumor. The purpose of this study was to investigate the clinicopathological features of parotid LEC. METHODS: All patients clinicopathological information diagnosed parotid LEC from 2005 to 2017 were analyzed. RESULTS: A total of 146 cases of parotid LECs were identified. Of these, 126 (86.3%) were primary and 20 (13.7%) were secondary LECs. Patients with secondary LEC tended to have tumors with earlier TNM staging than those with primary (p = 0.031). The tumor cells in 87 (94.6%, 87/92) cases tested positive for Epstein-Barr virus (EBV). Cervical node metastases were present at diagnosis in 46 (31.5%) cases. Overall survival at 5 and 10 years was 97.0% and 90.8%, respectively. Older age was an adverse prognostic indicator for overall survival (p < 0.001). CONCLUSIONS: Parotid LEC is associated with EBV and an increased rate of cervical node metastases. However, most patients, especially younger ones, have a good prognosis.


Assuntos
Carcinoma de Células Grandes , Carcinoma de Células Escamosas , Infecções por Vírus Epstein-Barr , Neoplasias Parotídeas , Carcinoma de Células Escamosas/patologia , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , Humanos , Glândula Parótida/patologia , Glândula Parótida/cirurgia , Neoplasias Parotídeas/patologia , Neoplasias Parotídeas/cirurgia
7.
J Evid Based Med ; 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35919928

RESUMO

OBJECTIVE: To evaluate the reporting quality of single-patient (N-of-1) trials and protocols based on the CONSORT Extension for N-of-1 trials (CENT) statement and the standard protocol items: recommendations for interventional trials (SPIRIT) extension and elaboration for N-of-1 trials (SPENT) checklist to examine the factors that influenced reporting quality. METHODS: Four electronic databases were searched to identify N-of-1 trials and protocols from 2015 to 2020. Quality was assessed by two reviewers. We calculated the overall scores based on binary responses in which "Yes" was scored as 1 (if the item was fully reported), and "No" was scored as 0 (if the item was not clearly reported or not definitely stated). RESULTS: A total of 78 publications (55 N-of-1 trials and 23 protocols) were identified. The mean reporting score (SD) of the N-of-1 trials and protocols were 29.24 (0.89) and 29.61 (1.83), respectively. For the items related to outcomes, sample size, allocation concealment protocol, and informed consent materials, the reporting quality was low. Our results showed that the year of publication (t = -0.793, p = 0.872 for the trials and t = 1.352, p = 0.623 for the protocols) and the impact factor of the journal (t = 1.416, p = 0.619 for the trials and t = 0.359, p = 0.667 for the protocols) were not factors associated with better reporting quality. CONCLUSION: With the publication of the CENT 2015 statement and the SPENT 2019 checklist, authors should adhere to the relevant reporting guidelines and improve the reporting quality of N-of-1 trials and protocols.

8.
Transl Androl Urol ; 11(6): 859-866, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35812190

RESUMO

Background: This paper aimed to identify the key genes and potential mechanisms of renal fibrosis, and provide methods of evaluation and new ideas for the early diagnosis and treatment of renal fibrosis. Methods: The GSE102515 dataset was searched from the Gene Expression Omnibus (GEO) database was searched, the differential genes were screened out, and the down-regulated and up-regulated genes were identified. Enrichment analysis of differential genes in the development of renal fibrosis was carried out using the DAVID database, differential genes were analyzed using the STRING database, and Cytoscape software was used for visual processing. Results: Eighteen up-regulated genes and ten down-regulated genes were screened. Differential genes are mainly involved in the integrin-mediated signaling pathway and mitotic sister chromatid binding, etc. We found that the molecular functions (MFs) of the differential genes are phospholipid binding and regulatory region DNA binding, etc. Moreover, the cellular components (CCs) of the differential genes are mainly related to low-density lipoprotein (LDL) particles and nuclei. Screening revealed that ADM, ARRB1, AVPR2, CCR1, MTNR1A, PTH, and S1PR2 were core genes in the interaction network of renal fibrosis risk-related proteins. Conclusions: In this study, the differential genes in the occurrence of renal fibrosis were screened out via dataset analysis. It was found that ADM, ARRB1, AVPR2, CCR1, MTNR1A, PTH, and S1PR2 may be important participants in the development of renal fibrosis, which provides analytical support for the identification of valuable markers of renal fibrosis.

9.
Artigo em Inglês | MEDLINE | ID: mdl-35896151

RESUMO

C-reactive protein (CRP), a systemic marker of diagnosing chronic inflammation, has been associated with the incidence of multiple types of cancer. However, little is known about the impact of CRP on lung cancer incidence in Chinese population. A total of 97,950 participants without cancer at baseline (2006-2007) of the Kailuan Cohort Study were followed up. The concentration of plasma high-sensitivity CRP (hsCRP) was tested for all participants at baseline interview. Multivariable Cox proportional hazards regression models were used to assess the association between levels of hsCRP and incident lung cancer. During 8.7-year follow-up, 890 incident lung cancer cases occurred and were divided into three groups according to the level of hsCRP. The risk of incident lung cancer was significantly increased with elevated levels of hsCRP [hazard ratio (HR)Medium/Low=1.21, 95% confidence interval (CI)=1.03-1.42; HRHigh/Low=1.42, 95%CI=1.20-1.68; Ptrend<0.001], compared to the low group after adjusting confounders. Moreover, after stratifying by BMI, the significantly positive associations between the hsCRP level and the risk of lung cancer were found among those with BMI<24 (HRHigh/Low=1.51, 95%CI=1.18-1.94; Ptrend=0.001) and BMI=24-28 (HRHigh/Low=1.47, 95%CI=1.13-1.92; Ptrend=0.003), but not among those with BMI≥28 (HRHigh/Low=1.01, 95%CI=0.64-1.57; Ptrend=0.991). There was an antagonistic interaction between hsCRP levels and BMI that contributed to development of lung cancer (Pinteraction=0.049). In conclusion, these findings indicate a dose-dependent relationship between hsCRP and lung cancer risk among Chinese population, especially in non-obese participants, suggesting that CRP could serve as a potential biomarker for prediction of lung cancer risk and identification of high-risk population.

10.
Artigo em Inglês | MEDLINE | ID: mdl-35900139

RESUMO

RATIONALE: Over 40% lung cancer cases occurred in never-smokers in China. However, high-risk never-smokers were precluded benefiting from the lung cancer screening as most screening guidelines did not consider them. OBJECTIVES: We sought to develop and validate prediction models for three-year lung cancer risks for never- and ever-smokers (China NCC-LCm2021 models). METHODS: 425 626 never-smokers and 128 952 ever-smokers from the National Lung Cancer Screening program were used as the training cohort and analyzed using multivariable Cox models. Models were validated in two independent prospective cohorts: one included 369 650 never-smokers and 107 678 ever-smokers (841 and 421 lung cancers), and the other included 286 327 never-smokers and 78 469 ever-smokers (503 and 127 lung cancers). MEASUREMENTS AND RESULTS: The areas under the receiver operating characteristic curves (AUC) in the two validation cohorts were 0.698 and 0.673 for never-smokers, and 0.728 and 0.752 for ever-smokers. Our models had higher AUCs than other existing models and were well calibrated in the validation cohort. The China NCC-LCm2021 ≥0.47% threshold was suggested for never-smokers and ≥0.51% for ever-smokers. Moreover, we provided a range of threshold options with corresponding expected screening outcomes, screening target, and screening efficiency. CONCLUSION: The construction of the China NCC-LCm2021 models can accurately reflect individuals' risk of lung cancer, regardless of smoking status. Our models can significantly increase the feasibility of conducting centralized lung cancer screening programs, because we provided justified thresholds to define the high-risk population of lung cancer and threshold options to adapt different configuration of medical resources.

11.
Sci Rep ; 12(1): 12358, 2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35853973

RESUMO

We aim to determine whether ischemic stroke(IS)-related PRSs are also associated with and further predict 3-year all-cause mortality. 1756 IS patients with European ancestry were randomly split into training (n = 1226) and testing (n = 530) groups with 3-year post-event observations. Univariate Cox proportional hazards regression model (CoxPH) was used for primary screening of individual prognostic PRSs. Only the significantly associated PRSs and clinical risk factors with the same direction for a causal relationship with IS were used to construct a multivariate CoxPH. Feature selection was conducted by the LASSO method. After feature selection, a prediction model with 11 disease-associated pathway-specific PRSs outperformed the base model, as demonstrated by a higher concordance index (0.751, 95%CI [0.693-0.809] versus 0.729, 95%CI [0.676-0.782]) in the testing sample. A PRS derived from endothelial cell apoptosis showed independent predictability in the multivariate CoxPH (Hazard Ratio = 1.193 [1.027-1.385], p = 0.021). These PRSs fine-tuned the model by better stratifying high, intermediate, and low-risk groups. Several pathway-specific PRSs were associated with clinical risk factors in an age-dependent manner and further confirmed some known etiologies of IS and all-cause mortality. In conclusion, Pathway-specific PRSs for IS are associated with all-cause mortality, and the integrated multivariate risk model provides prognostic value in this context.


Assuntos
AVC Isquêmico , Herança Multifatorial , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , AVC Isquêmico/genética , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco
12.
Biochim Biophys Acta Mol Basis Dis ; 1868(10): 166480, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35811033

RESUMO

Activation of the innate immune system through toll-like receptors (TLRs) has been repeatedly demonstrated in non-alcoholic fatty liver disease (NAFLD) and several TLRs have been shown to contribute. Myeloid differentiation primary response 88 (MyD88) is as an adapter protein for the activation of TLRs and bridges TLRs to NF-κB-mediated inflammation in macrophages. However, whether myeloid cell MyD88 contributes to NAFLD are largely unknown. To test this approach, we generated macrophage-specific MyD88 knockout mice and show that these mice are protected against high-fat diet (HFD)-induced hepatic injury, lipid accumulation, and fibrosis. These protective effects were associated with reduced macrophage numbers in liver tissues and surpassed inflammatory responses. In cultured macrophages, saturated fatty acid palmitate utilizes MyD88 to activate NF-κB and induce inflammatory and fibrogenic factors. In hepatocytes, these factors may cause lipid accumulation and a further elaboration of inflammatory cytokines. In hepatic stellate cells, macrophage-derived factors, especially TGF-ß, cause activation and hepatic fibrosis. We further show that pharmacological inhibition of MyD88 is also able to reduce NAFLD injury in HFD-fed mice. Therefore, our study has provided empirical evidence that macrophage MyD88 participates in HFD-induced NAFLD and could be targeted to prevent the development and progression of NAFLD/NASH.


Assuntos
Fator 88 de Diferenciação Mieloide , Hepatopatia Gordurosa não Alcoólica , Animais , Deleção de Genes , Lipídeos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/prevenção & controle
13.
J Virol ; 96(14): e0080622, 2022 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-35862697

RESUMO

Baculoviruses initiate oral infection in the highly alkaline midgut of insects via a group of envelope proteins called per os infectivity factors (PIFs). To date, no high-resolution structural information has been reported for any PIF. Here, we present the crystal structure of the PIF5 ectodomain (PIF5e) from Autographa californica multiple nucleopolyhedrovirus (AcMNPV) at a 2.2-Å resolution. It revealed an open cavity between the N-terminal E1 domain and the C-terminal E2 domain and a cysteine-rich region with three pairs of disulfide bonds in the E2 domain. Multiple conserved intramolecular interactions within PIF5 are essential for maintaining its tertiary structure. Two conserved arginines (Arg8 and Arg74) play critical roles in E1-E2 interactions, and mutagenesis analysis supported their crucial role in oral infection. Importantly, the reduction in the oral infectivity of the Arg8, Arg74, or cysteine mutant viruses was related to the proteolytic cleavage of PIF5 by the endogenous protease embedded in occlusion bodies during alkaline treatment. This suggested that the structural stability of PIF5 under physiological conditions in the insect midgut is critical for baculoviral oral infectivity. IMPORTANCE Per os infection mediated by PIFs is the highly complex mechanism by which baculoviruses initiate infection in insects. Previous studies revealed that multiple PIF proteins form a large PIF complex on the envelope of virions, while PIF5 functions independently of the PIF complex. Here, we report the crystal structure of AcMNPV PIF5e, which, to our knowledge, is the first atomic structure reported for a PIF protein. The structure revealed the precise locations of three previously proposed disulfide bonds and other conserved intramolecular interactions, which are important for the structural stability of PIF5 and are also essential for oral infectivity. These findings advance our understanding of the molecular mechanism of baculovirus oral infection under alkaline conditions.


Assuntos
Nucleopoliedrovírus , Proteínas do Envelope Viral , Animais , Cisteína/química , Dissulfetos/química , Insetos , Nucleopoliedrovírus/química , Nucleopoliedrovírus/genética , Conformação Proteica , Spodoptera , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genética
14.
Front Genet ; 13: 875617, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35846125

RESUMO

Purpose: Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors of the head and neck, while metastasis is the main cause of OSCC-related death. There is an urgent need to explore novel prognostic biomarkers and identify biological targets related to metastasis in OSCC treatment. Methods: Analysis of differential expression was performed using datasets in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Immunohistochemistry (IHC) was conducted to assess the expression of betacellulin (BTC) in OSCC. SCC4 and CAL27 cells were used for in vitro experiments, in which CCK-8, transwell assays, and wounding healing assays were performed to verify the biological functions of BTC. The role of BTC in EMT was analyzed by EMT score and Western blot. Results: Through the analysis of the mRNA expression profile data from TCGA database in OSCC, we found that only low expression of BTC was significantly correlated with a poor prognosis in OSCC patients. The results of IHC assays and TCGA databases showed that the expression level of BTC was related to the tumor stage, histological grade, and metastasis status. In vitro analysis showed that overexpression of BTC significantly suppressed the proliferation and migration of OSCC cells. Furthermore, we confirmed that BTC could affect EMT through the PI3K-AKT signaling pathway. Conclusion: The overexpression of BTC suppresses the proliferation, migration, and EMT of OSCC cells via the PI3K-AKT pathways, leading to a better prognosis in OSCC. BTC may be used as a novel molecular marker to assess the prognosis of OSCC patients.

15.
J Clin Med ; 11(14)2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35887865

RESUMO

(1) Background: Stroke incidence and outcomes are influenced by socioeconomic status. There is a paucity of reported population-level studies regarding these determinants. The goal of this ecological analysis was to determine the county-level associations of social determinants of stroke hospitalization and death rates in the United States. (2) Methods: Publicly available data as of 9 April 2021, for the socioeconomic factors and outcomes, was extracted from the Centers for Disease Control and Prevention. The outcomes of interest were "all stroke hospitalization rates per 1000 Medicare beneficiaries" (SHR) and "all stroke death rates per 100,000 population" (SDR). We used a multivariate binomial generalized linear mixed model after converting the outcomes to binary based on their median values. (3) Results: A total of 3226 counties/county-equivalents of the states and territories in the US were analyzed. Heart disease prevalence (odds ratio, OR = 2.03, p < 0.001), blood pressure medication nonadherence (OR = 2.02, p < 0.001), age-adjusted obesity (OR = 1.24, p = 0.006), presence of hospitals with neurological services (OR = 1.9, p < 0.001), and female head of household (OR = 1.32, p = 0.021) were associated with high SHR while cost of care per capita for Medicare patients with heart disease (OR = 0.5, p < 0.01) and presence of hospitals (OR = 0.69, p < 0.025) were associated with low SHR. Median household income (OR = 0.6, p < 0.001) and park access (OR = 0.84, p = 0.016) were associated with low SDR while no college degree (OR = 1.21, p = 0.049) was associated with high SDR. (4) Conclusions: Several socioeconomic factors (e.g., education, income, female head of household) were found to be associated with stroke outcomes. Additional research is needed to investigate intermediate and potentially modifiable factors that can serve as targeted interventions.

16.
Artigo em Inglês | MEDLINE | ID: mdl-35897515

RESUMO

Community-academic partnerships (CAPs) are being increasingly used to study and address health disparity issues. CAPs help to create new bodies of knowledge and innovative solutions to community problems, which benefits the community and academia. Supported by a grant, a partnership was formed between an academic research team and a community health organization to analyze and interpret data collected from the caregivers of asthmatic African American children living in urban low-income households. Using a case study approach, we discuss how we built a healthy CAP and the lessons learned from the process. Our analysis was guided by the six main factors that facilitate success in developing collaborative relationships, including (1) environment; (2) membership; (3) process and structure; (4) communication; (5) purpose; and (6) resources. Based on these six factors, we describe our collaboration process, challenges, and areas for improvement. We aimed to provide a "points-to-consider" roadmap for academic and community partners to establish and maintain a mutually beneficial and satisfactory relationship. Collaborating with community members and organizations provides unique opportunities for researchers and students to apply their skills and knowledge from textbooks and the classroom, engage with community members, and improve real-life community needs. Building a constructive CAP involves efforts, energy, and resources from both parties. The six major themes derived from our project offer suggestions for building a healthy, collaborative, and productive relationship that best serves communities in the future.


Assuntos
Pesquisa Participativa Baseada na Comunidade , Relações Comunidade-Instituição , Criança , Humanos , Grupos Minoritários , Pobreza , Qualidade de Vida
17.
Neurobiol Dis ; 172: 105822, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35868435

RESUMO

Patients with epilepsy develop reproductive endocrine comorbidities at a rate higher than that of the general population. Clinical studies have identified disrupted luteinizing hormone (LH) release patterns in patients of both sexes, suggesting potential epilepsy-associated changes in hypothalamic gonadotropin-releasing hormone (GnRH) neuron function. In previous work, we found that GnRH neuron firing is increased in diestrous females and males in the intrahippocampal kainic acid (IHKA) mouse model of temporal lobe epilepsy. Notably, GABAA receptor activation is depolarizing in adult GnRH neurons. Therefore, here we tested the hypothesis that increased GnRH neuron firing in IHKA mice is associated with increased GABAergic drive to GnRH neurons. When ionotropic glutamate receptors (iGluRs) were blocked to isolate GABAergic postsynaptic currents (PSCs), no differences in PSC frequency were seen between GnRH neurons from control and IHKA diestrous females. In the absence of iGluR blockade, however, GABA PSC frequency was increased in GnRH neurons from IHKA females with disrupted estrous cycles, but not saline-injected controls nor IHKA females without estrous cycle disruption. GABA PSC amplitude was also increased in IHKA females with disrupted estrous cycles. These findings suggest the presence of an iGluR-dependent increase in feed-forward GABAergic transmission to GnRH neurons specific to IHKA females with comorbid cycle disruption. In males, GABA PSC frequency and amplitude were unchanged but PSC duration was reduced. Together, these findings suggest that increased GABA transmission helps drive elevated firing in IHKA females on diestrus and indicate the presence of a sex-specific hypothalamic mechanism underlying reproductive endocrine dysfunction in IHKA mice.

18.
J Inflamm Res ; 15: 3925-3940, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35860230

RESUMO

Background: Sepsis mortality has remained unchanged for greater than a decade, and early recognition continues to be the most important factor in mortality outcome. Plasma resistin concentration is increased in sepsis, but its mechanism and clinical relevance is unclear. As one function, resistin interacts with toll-like receptor 4 in competition with lipopolysaccharide, a main component of the gram-negative bacterial cell wall. It is not known if the type of infection leading to sepsis influences resistin production. The objective of this study was to investigate whether 1) early plasma resistin concentration can predict mortality, 2) elevated plasma resistin concentration is associated with clinical disease severity scores, such as SOFA, mSOFA and APACHE II, and 3) plasma resistin concentrations differ between gram negative versus other etiologies of sepsis. Methods: This was an exploratory study in the framework of a prospective observational design. Peripheral venous blood samples were obtained from subjects admitted to the intensive care unit at clinical recognition of sepsis (0 hour) and at 6 and 24 hours. Vasopressor utilization was not a requirement for inclusion. Plasma was analyzed for resistin concentration by ELISA. Cytokine concentrations including IL-6, IL-8, and IL-10 were determined by cytokine bead array. Cytokine data were evaluated against publicly available sepsis RNA expression datasets to compare protein versus RNA expression levels in predicting clinical disease state. Clinical data were collected from electronic health records for clinical severity index calculations and context for interpretation of resistin and cytokine concentrations. Subjects were followed up to 60 days, or until death, whichever came first. Statistical analysis was completed with R package and SPSS software. Results: Resistin levels were elevated in subjects admitted to the intensive care unit with sepsis. Four-hundred subjects were screened with 45 subjects included in the final analysis. Thirteen of 45 patients were non-survivors. Mortality within 60 days correlated with significantly higher resistin concentrations than in survivors. A resistin concentration of >126 ng/mL at clinical recognition of sepsis and >197 ng/mL within the first 24 hours were associated with mortality within 60 days with an area under the curve of 0.82 and 0.88, respectively. Most subjects with resistin concentration greater than these threshold values were deceased prior to 30 days. Resistin concentrations correlated with SOFA, mSOFA, and APACHE II scores in addition to having association with increases in inflammatory and sepsis biomarkers. These associations were validated with analysis of RNA expression datasets. Conclusion: Plasma resistin concentrations of >126 ng/mL at clinical recognition of sepsis and >197 ng/mL within the first 24 hours of clinical sepsis recognition are associated with all-cause mortality. Resistin concentration within this timeframe also has comparable mortality association to well-validated clinical severity indices of SOFA, mSOFA, and APACHE II scores.

19.
Sci Total Environ ; : 157472, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35870598

RESUMO

The large-scale use and release of antibiotics may create selective pressure on antibiotic resistance genes (ARGs), causing potential harm to human health. River ecosystems have long been considered repositories of antibiotics and ARGs. Therefore, the distribution characteristics and seasonal variation in antibiotics and ARGs in the surface water of the main stream and tributaries of the Chishui River were studied. The concentrations of antibiotics in the dry season and rainy season were 54.18-425.74 ng/L and 66.57-256.40 ng/L, respectively, gradually decreasing along the river direction. The results of antibiotics in the dry season and rainy season showed that livestock and poultry breeding were the main sources in the surface water of the Chishui River basin. Risk assessments indicated high risk levels of OFL in both seasons. In addition, analysis of ARGs and microbial community diversity showed that sul1 and sul3 were the main ARGs in the two seasons. The highest abundance of ARGs was 7.70 × 107 copies/L, and intl1 was significantly positively correlated with all resistance genes (p < 0.01), indicating that it can significantly promote the transmission of ARGs. Proteobacteria were the dominant microorganisms in surface water, with a higher average abundance in the dry season (60.64 %) than in the rainy season (39.53 %). Finally, correlation analyses were performed between ARGs and antibiotics, microbial communities and heavy metals. The results showed that there was a significant positive correlation between ARGs and most microorganisms and heavy metals (p < 0.01), indicating that occurrence and transmission in the environment are influenced by various environmental factors and cross-selection. In conclusion, the persistent residue and transmission of ARGs and their transfer to pathogens are a great threat to human health and deserve further study and attention.

20.
Chin Med J (Engl) ; 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35830209

RESUMO

BACKGROUND: Non-smokers account for a large proportion of lung cancer patients, especially in Asia, but the attention paid to them is limited compared with smokers. In non-smokers, males display a risk for lung cancer incidence distinct from the females-even after excluding the influence of smoking; but the knowledge regarding the factors causing the difference is sparse. Based on a large multicenter prospective cancer screening cohort in China, we aimed to elucidate the interpretable sex differences caused by known factors and provide clues for primary and secondary prevention. METHODS: Risk factors including demographic characteristics, lifestyle factors, family history of cancer, and baseline comorbidity were obtained from 796,283 Chinese non-smoking participants by the baseline risk assessment completed in 2013 to 2018. Cox regression analysis was performed to assess the sex difference in the risk of lung cancer, and the hazard ratios (HRs) that were adjusted for different known factors were calculated and compared to determine the proportion of excess risk and to explain the existing risk factors. RESULTS: With a median follow-up of 4.80 years, 3351 subjects who were diagnosed with lung cancer were selected in the analysis. The lung cancer risk of males was significantly higher than that of females; the HRs in all male non-smokers were 1.29 (95% confidence interval [CI]: 1.20-1.38) after adjusting for the age and 1.38 (95% CI: 1.28-1.50) after adjusting for all factors, which suggested that known factors could not explain the sex difference on the risk of lung cancer in the males who never smoked. Known factors were 7% (|1.29-1.38|/1.29) more harmful in women than in men. For adenocarcinoma, women showed excess risk higher than men, contrary to squamous cell carcinoma; after adjusting for all factors, 47% ([1.30-1.16]/[1.30-1]) and 4% ([7.02-6.75]/[7.02-1])) of the excess risk was explainable in adenocarcinoma and squamous cell carcinoma. The main causes of gender differences in lung cancer risk were lifestyle factors, baseline comorbidity, and family history. CONCLUSIONS: Significant gender differences in the risk of lung cancer were discovered in China non-smokers. Existing risk factors did not explain the excess lung cancer risk of all non-smoking men, and the internal causes for the excess risk still need to be explored; most known risk factors were more harmful to non-smoking women; further exploring the causes of the sex difference would help to improve the prevention and screening programs and protect the non-smoking males from lung cancers.

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