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1.
Am J Epidemiol ; 193(9): 1242-1252, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-38775277

RESUMO

Limited estimates exist on risk factors for epithelial ovarian cancer (EOC) in Asian, Hispanic, and Native Hawaiian/Pacific Islander women. Participants in this study included 1734 Asian (n = 785 case and 949 control participants), 266 Native Hawaiian/Pacific Islander (n = 99 case and 167 control participants), 1149 Hispanic (n = 505 case and 644 control participants), and 24 189 White (n = 9981 case and 14 208 control participants) from 11 studies in the Ovarian Cancer Association Consortium. Logistic regression models estimated odds ratios (ORs) and 95% CIs for risk associations by race and ethnicity. Heterogeneity in EOC risk associations by race and ethnicity (P ≤ .02) was observed for oral contraceptive (OC) use, parity, tubal ligation, and smoking. We observed inverse associations with EOC risk for OC use and parity across all groups; associations were strongest in Native Hawaiian/Pacific Islander and Asian women. The inverse association for tubal ligation with risk was most pronounced for Native Hawaiian/Pacific Islander participants (odds ratio (OR) = 0.25; 95% CI, 0.13-0.48) compared with Asian and White participants (OR = 0.68 [95% CI, 0.51-0.90] and OR = 0.78 [95% CI, 0.73-0.85], respectively). Differences in EOC risk factor associations were observed across racial and ethnic groups, which could be due, in part, to varying prevalence of EOC histotypes. Inclusion of greater diversity in future studies is essential to inform prevention strategies. This article is part of a Special Collection on Gynecological Cancers.


Assuntos
Carcinoma Epitelial do Ovário , Neoplasias Ovarianas , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Asiático , Carcinoma Epitelial do Ovário/etnologia , Carcinoma Epitelial do Ovário/epidemiologia , Estudos de Casos e Controles , Anticoncepcionais Orais/efeitos adversos , Etnicidade , Hispânico ou Latino , Modelos Logísticos , Havaiano Nativo ou Outro Ilhéu do Pacífico , Razão de Chances , Neoplasias Ovarianas/etnologia , Neoplasias Ovarianas/epidemiologia , Paridade , Fatores de Risco , Fumar/etnologia , Fumar/epidemiologia , Esterilização Tubária/estatística & dados numéricos , Estados Unidos/epidemiologia , Brancos
2.
Proc Natl Acad Sci U S A ; 118(32)2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34362847

RESUMO

Increasingly, severe wildfires have led to declines in biodiversity across all of Earth's vegetated biomes [D. B. McWethy et al., Nat. Sustain. 2, 797-804 (2019)]. Unfortunately, the displacement of Indigenous peoples and place-based societies that rely on and routinely practice fire stewardship has resulted in significant declines in biodiversity and the functional roles of people in shaping pyrodiverse systems [R. Bliege Bird et al., Proc. Natl. Acad. Sci. U.S.A. 117, 12904-12914 (2020)]. With the aim of assessing the impacts of Indigenous fire stewardship on biodiversity and species function across Earth's major terrestrial biomes, we conducted a review of relevant primary data papers published from 1900 to present. We examined how the frequency, seasonality, and severity of human-ignited fires can improve or reduce reported metrics of biodiversity and habitat heterogeneity as well as changes to species composition across a range of taxa and spatial and temporal scales. A total of 79% of applicable studies reported increases in biodiversity as a result of fire stewardship, and 63% concluded that habitat heterogeneity was increased by the use of fire. All studies reported that fire stewardship occurred outside of the window of uncontrollable fire activity, and plants (woody and nonwoody vegetation) were the most intensively studied life forms. Three studies reported declines in biodiversity associated with increases in the use of high-severity fire as a result of the disruption of Indigenous-controlled fire regimes with the onset of colonization. Supporting Indigenous-led fire stewardship can assist with reviving important cultural practices while protecting human communities from increasingly severe wildfires, enhancing biodiversity, and increasing ecosystem heterogeneity.


Assuntos
Biodiversidade , Conservação dos Recursos Naturais/métodos , Incêndios , Animais , Aves , Ecossistema , Humanos , Povos Indígenas , Mamíferos , Répteis , Madeira
3.
PLoS Genet ; 17(6): e1009594, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34097698

RESUMO

The number of grains per panicle is an important yield-related trait in cereals which depends in part on panicle branching complexity. One component of this complexity is the number of secondary branches per panicle. Previously, a GWAS site associated with secondary branch and spikelet numbers per panicle in rice was identified. Here we combined gene capture, bi-parental genetic population analysis, expression profiling and transgenic approaches in order to investigate the functional significance of a cluster of 6 ANK and ANK-TPR genes within the QTL. Four of the ANK and ANK-TPR genes present a differential expression associated with panicle secondary branch number in contrasted accessions. These differential expression patterns correlate in the different alleles of these genes with specific deletions of potential cis-regulatory sequences in their promoters. Two of these genes were confirmed through functional analysis as playing a role in the control of panicle architecture. Our findings indicate that secondary branching diversity in the rice panicle is governed in part by differentially expressed genes within this cluster encoding ANK and ANK-TPR domain proteins that may act as positive or negative regulators of panicle meristem's identity transition from indeterminate to determinate state.


Assuntos
Anquirinas/genética , Oryza/genética , Sequências Repetitivas de Ácido Nucleico , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Locos de Características Quantitativas
4.
5.
Emerg Infect Dis ; 29(5): 1002-1006, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37015283

RESUMO

We analyzed 1,303 SARS-CoV-2 whole-genome sequences from Vietnam, and found the Alpha and Delta variants were responsible for a large nationwide outbreak of COVID-19 in 2021. The Delta variant was confined to the AY.57 lineage and caused >1.7 million infections and >32,000 deaths. Viral transmission was strongly affected by nonpharmaceutical interventions.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , SARS-CoV-2/genética , Vietnã/epidemiologia , Surtos de Doenças
6.
Kidney Int ; 103(1): 42-52, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36377113

RESUMO

Blood pressure is regulated by a complex neurohumoral system including the renin-angiotensin-aldosterone system, natriuretic peptides, endothelial pathways, the sympathetic nervous system, and the immune system. This review charts the evolution of our understanding of the genomic basis of hypertension at increasing resolution over the last 5 decades from monogenic causes to polygenic associations, spanning ∼30 monogenic rare variants and >1500 single nucleotide variants. Unexpected early wins from blood pressure genomics include deepening of our understanding of the complex causation of hypertension; refinement of causal estimates bidirectionally between blood pressure, risk factors, and outcomes through Mendelian randomization; risk stratification using polygenic risk scores; and opportunities for precision medicine and drug repurposing.


Assuntos
Hipertensão , Humanos , Pressão Sanguínea/genética , Sistema Renina-Angiotensina/genética , Fatores de Risco , Genômica
7.
Br J Cancer ; 128(1): 137-147, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36323878

RESUMO

BACKGROUND: Recently, we showed a >60% difference in 5-year survival for patients with tubo-ovarian high-grade serous carcinoma (HGSC) when stratified by a 101-gene mRNA expression prognostic signature. Given the varied patient outcomes, this study aimed to translate prognostic mRNA markers into protein expression assays by immunohistochemistry and validate their survival association in HGSC. METHODS: Two prognostic genes, FOXJ1 and GMNN, were selected based on high-quality antibodies, correlation with protein expression and variation in immunohistochemical scores in a preliminary cohort (n = 134 and n = 80, respectively). Six thousand four hundred and thirty-four (FOXJ1) and 5470 (GMNN) formalin-fixed, paraffin-embedded ovarian neoplasms (4634 and 4185 HGSC, respectively) represented on tissue microarrays from the Ovarian Tumor Tissue Analysis consortium underwent immunohistochemical staining and scoring, then univariate and multivariate survival analysis. RESULTS: Consistent with mRNA, FOXJ1 protein expression exhibited a linear, increasing association with improved overall survival in HGSC patients. Women with >50% expression had the most favourable outcomes (HR = 0.78, 95% CI 0.67-0.91, p < 0.0001). GMNN protein expression was not significantly associated with overall HSGC patient survival. However, HGSCs with >35% GMNN expression showed a trend for better outcomes, though this was not significant. CONCLUSION: We provide foundational evidence for the prognostic value of FOXJ1 in HGSC, validating the prior mRNA-based prognostic association by immunohistochemistry.


Assuntos
Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/patologia , Prognóstico , Análise de Sobrevida , RNA Mensageiro/genética , Cistadenocarcinoma Seroso/patologia , Biomarcadores Tumorais/análise , Fatores de Transcrição Forkhead/genética
8.
Gynecol Oncol ; 168: 23-31, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36368129

RESUMO

OBJECTIVE: Mucinous ovarian carcinoma (MOC) is a rare histotype of ovarian cancer, with low response rates to standard chemotherapy, and very poor survival for patients diagnosed at advanced stage. There is a limited understanding of the MOC immune landscape, and consequently whether immune checkpoint inhibitors could be considered for a subset of patients. METHODS: We performed multicolor immunohistochemistry (IHC) and immunofluorescence (IF) on tissue microarrays in a cohort of 126 MOC patients. Cell densities were calculated in the epithelial and stromal components for tumor-associated macrophages (CD68+/PD-L1+, CD68+/PD-L1-), T cells (CD3+/CD8-, CD3+/CD8+), putative T-regulatory cells (Tregs, FOXP3+), B cells (CD20+/CD79A+), plasma cells (CD20-/CD79a+), and PD-L1+ and PD-1+ cells, and compared these values with clinical factors. Univariate and multivariable Cox Proportional Hazards assessed overall survival. Unsupervised k-means clustering identified patient subsets with common patterns of immune cell infiltration. RESULTS: Mean densities of PD1+ cells, PD-L1- macrophages, CD4+ and CD8+ T cells, and FOXP3+ Tregs were higher in the stroma compared to the epithelium. Tumors from advanced (Stage III/IV) MOC had greater epithelial infiltration of PD-L1- macrophages, and fewer PD-L1+ macrophages compared with Stage I/II cancers (p = 0.004 and p = 0.014 respectively). Patients with high epithelial density of FOXP3+ cells, CD8+/FOXP3+ cells, or PD-L1- macrophages, had poorer survival, and high epithelial CD79a + plasma cells conferred better survival, all upon univariate analysis only. Clustering showed that most MOC (86%) had an immune depleted (cold) phenotype, with only a small proportion (11/76,14%) considered immune inflamed (hot) based on T cell and PD-L1 infiltrates. CONCLUSION: In summary, MOCs are mostly immunogenically 'cold', suggesting they may have limited response to current immunotherapies.


Assuntos
Antígeno B7-H1 , Neoplasias Ovarianas , Humanos , Feminino , Antígeno B7-H1/genética , Carcinoma Epitelial do Ovário/patologia , Neoplasias Ovarianas/tratamento farmacológico , Linfócitos T CD8-Positivos , Fatores de Transcrição Forkhead/uso terapêutico , Linfócitos do Interstício Tumoral , Microambiente Tumoral
9.
Med Mycol ; 61(10)2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37771088

RESUMO

Host non-T cell markers to aid in the diagnosis of cryptococcal meningoencephalitis (CM) have not been identified. In this case-control study, we characterized antibody and B cell profiles in HIV-negative and HIV-positive Vietnamese individuals of the Kinh ethnicity recently diagnosed with CM and controls. The study included 60 HIV-negative with no known immunocompromising condition and 60 HIV-positive individuals, with 30 CM cases and 30 controls in each group. Participants were matched by age, sex, HIV serostatus, and CD4 count in the HIV-positive group. Plasma immunoglobulin (Ig) levels, including IgG1, IgG2, IgM, and IgA, Cryptococcus spp. glucuronoxylomannan (GXM)- and laminarin (branched ${\rm{\beta }}$-[1-3]-glucan)-binding IgG, IgM, IgA levels, and peripheral blood B cell subsets were measured. Logistic regression, principal component, and mediation analyses were conducted to assess associations between antibody, B cell levels, and CM. The results showed that GXM-IgG levels were higher and IgG1 and IgG2 were lower in CM cases than controls, regardless of HIV status. In HIV-negative individuals, IgG2 mediated an inverse association between CD19+CD27+CD43+CD5- (B-1b-like) cells and CM. In HIV-positive individuals, lower levels of IgA, laminarin-IgA, and CD19+CD27+IgM+IgD- (IgM+ memory B) cells were each associated with CM. The shared and distinct antibody and B cell profiles identified in HIV-negative and HIV-positive CM cases may inform the identification of non-T-cell markers of CM risk or unsuspected disease, particularly in HIV-negative individuals.


Unlike cryptococcal meningitis (CM) in HIV-positive individuals, there are no known biomarkers of risk in HIV-negative individuals and the diagnosis is often not suspected and delayed. This study identified non-T cells, including antibody and B cell CM-associated profiles that may guide cryptococcal antigen testing in HIV-negative individuals.


Assuntos
Cryptococcus neoformans , Infecções por HIV , Meningite Criptocócica , Meningoencefalite , Humanos , Estudos de Casos e Controles , Infecções por HIV/complicações , Infecções por HIV/veterinária , Imunoglobulina M , Imunoglobulina G , Meningoencefalite/veterinária , Imunoglobulina A , Meningite Criptocócica/veterinária
10.
Cancer Causes Control ; 33(6): 913-918, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35302182

RESUMO

BACKGROUND: Although smoking is the primary risk factor for lung cancer, 15-25% of lung cancers occur in never smokers. Emerging evidence suggests lifestyle factors are associated with lung cancer risk, but few studies among never smokers exist. METHODS: A case-control study of never smokers within the Canadian Partnership for Tomorrow's Health was conducted. At recruitment, participants provided data on lifestyle, health history and sociodemographic factors. Incident lung cancers were identified through linkage with administrative health records. Cases (n = 190) were matched to controls (n = 760) on age, sex, and follow-up time. Logistic regression analyses, adjusted for matching factors and annual income, were used to identify associations between lifestyle factors and lung cancer risk. RESULTS: Consumption of < 5 servings of fruits and vegetables/day was associated with higher risk of lung cancer (OR 1.50, 95% CI 1.03-2.17). Short or long sleep (≤ 6 or > 9 h/night) was also associated with increased risk of lung cancer (OR 1.52, 95% CI 1.01-2.29). No associations were observed for obesity measures, alcohol consumption, or physical activity. CONCLUSION: Our findings provide evidence of a potential role between sleep, fruits and vegetable consumption, and lung cancer risk in a pan-Canadian, non-smoking population. However, the sample size is modest, and further investigation is needed.


Assuntos
Neoplasias Pulmonares , Fumantes , Canadá/epidemiologia , Estudos de Casos e Controles , Humanos , Estilo de Vida , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Estudos Prospectivos , Fatores de Risco , Verduras
11.
NMR Biomed ; 35(11): e4792, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35767281

RESUMO

In 2016, the World Health Organization (WHO) updated the glioma classification by incorporating molecular biology parameters, including low-grade glioma (LGG). In the new scheme, LGGs have three molecular subtypes: isocitrate dehydrogenase (IDH)-mutated 1p/19q-codeleted, IDH-mutated 1p/19q-noncodeleted, and IDH-wild type 1p/19q-noncodeleted entities. This work proposes a model prediction of LGG molecular subtypes using magnetic resonance imaging (MRI). MR images were segmented and converted into radiomics features, thereby providing predictive information about the brain tumor classification. With 726 raw features obtained from the feature extraction procedure, we developed a hybrid machine learning-based radiomics by incorporating a genetic algorithm and eXtreme Gradient Boosting (XGBoost) classifier, to ascertain 12 optimal features for tumor classification. To resolve imbalanced data, the synthetic minority oversampling technique (SMOTE) was applied in our study. The XGBoost algorithm outperformed the other algorithms on the training dataset by an accuracy value of 0.885. We continued evaluating the XGBoost model, then achieved an overall accuracy of 0.6905 for the three-subtype classification of LGGs on an external validation dataset. Our model is among just a few to have resolved the three-subtype LGG classification challenge with high accuracy compared with previous studies performing similar work.


Assuntos
Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Glioma/patologia , Humanos , Isocitrato Desidrogenase/genética , Aprendizado de Máquina , Imageamento por Ressonância Magnética/métodos , Mutação/genética , Estudos Retrospectivos
12.
Int J Gynecol Cancer ; 32(4): 508-516, 2022 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-35078828

RESUMO

BACKGROUND: Survival benefits of post-operative systemic and radiation therapy in high-risk stage I endometrial cancer are uncertain. OBJECTIVE: To compare recurrence patterns and survival outcomes of post-surgical treatment in patients with high-risk stage I endometrial cancer and to determine whether adjuvant therapy significantly improves outcomes. METHODS: High-risk stage I endometrial cancer was defined as either stage IB grade 3 endometrioid histology or myoinvasive non-endometrioid histology. Consecutive patients diagnosed between January 2000 and December 2010 in eight cancer centers were included. Patients, disease, and treatment characteristics were summarized by descriptive statistics. Overall survival, disease-specific survival, and relapse-free survival were examined using Cox's proportional hazards regression and log-rank test. Survival curves were estimated using the Kaplan-Meier method. RESULTS: Of 2317 patients with stage I endometrial cancer, 414 patients had high-risk disease. Use of chemotherapy did not improve overall survival (relative risk (RR) 0.70, 95% CI 0.46 to 1.14, p=0.13) or disease-specific survival (RR 1.06, 95% CI 0.61 to 1.85, p=0.84). Significant improvement in recurrence-free survival was observed in patients who received chemotherapy (RR 0.61, 95% CI 0.39 to 0.95, p=0.03). Use of radiation therapy did not improve overall survival, recurrence-free survival, or disease-specific survival. Patients who received four cycles or fewer of chemotherapy versus five to six cycles had similar overall survival, disease-specific survival, and recurrence-free survival. CONCLUSIONS: Post-operative chemotherapy or radiation in stage I high-risk endometrial cancer is not associated with improved cancer-specific or overall survival. More than four cycles of chemotherapy did not improve survival compared with four cycles or fewer.


Assuntos
Neoplasias do Endométrio , Recidiva Local de Neoplasia , Quimioterapia Adjuvante , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/radioterapia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Radioterapia Adjuvante/métodos , Estudos Retrospectivos
13.
Sensors (Basel) ; 22(14)2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35890760

RESUMO

A trajectory tracking control for quadcopter unmanned aerial vehicle (UAV) based on a nonlinear robust backstepping algorithm and extended state/disturbance observer (ESDO) is presented in this paper. To obtain robust attitude stabilization and superior performance of three-dimension position tracking control, the construction of the proposed algorithm can be separated into three parts. First, a mathematical model of UAV negatively influenced by exogenous disturbances is established. Following, an extended state/disturbance observer using a general second-order model is designed to approximate undesirable influences of perturbations on the UAVs dynamics. Finally, a nonlinear robust controller is constructed by an integration of the nominal backstepping technique with ESDO to enhance the performance of attitude and position control mode. Robust stability of the closed-loop disturbed system is obtained and guaranteed through the Lyapunov theorem without precise knowledge of the upper bound condition of perturbations. Lastly, a numerical simulation is carried out and compared with other previous controllers to demonstrate the great advantage and effectiveness of the proposed control method.

14.
Environ Monit Assess ; 194(2): 65, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34993616

RESUMO

Microplastics (MPs) are small (< 5 mm) plastic particles that are widely found in marine, freshwater, terrestrial and atmospheric environments. Due to their prevalence and persistence, MPs are considered an emerging contaminant of environmental concern. The separation and quantitation of MPs from freshwater sediments is a challenging and critical issue. It is necessary to identify the fate and sources of MPs in the environment, minimise their release and adverse effects. Compared to marine sediments, standardised methods for extracting and estimating the amount of MPs in freshwater sediments are relatively limited. The present study focuses on MP recovery efficiency of four commonly used salt solutions (NaCl, NaI, CaCl2 and ZnCl2) for isolating MPs during the density separation step from freshwater sediment. Known combinations of artificial MP particles (PS, PE, PVC, PET, PP and HDPE) were spiked into standard river sediment. Extraction using NaI, ZnCl2 and NaCl solutions resulted in higher recovery rates from 37 to 97% compared to the CaCl2 solution (28-83%) and varied between polymer types. Low-density MPs (PE, HDPE, PP and PS) were more effectively recovered (> 87%) than the denser polymers (PET and PVC: 37 to 88.8%) using NaCl, NaI and ZnCl2 solutions. However, the effective flotation of ZnCl2 and NaI solutions is relatively expensive and unsafe to the environment, especially in the context of developing countries. Therefore, considering the efficiency, cost and environmental criteria, NaCl solution was selected. The protocol was then tested by extracting MPs from nine riverine sediment samples from the Red River Delta. Sediments collected from urban rivers were highly polluted by MPs (26,000 MPs items·kg-1 DW) compared to sediments located downstream. Using a NaCl solution was found to be effective in this case study and might also be used in long-term and large-scale MP monitoring programmes in Vietnam.


Assuntos
Microplásticos , Poluentes Químicos da Água , Monitoramento Ambiental , Sedimentos Geológicos , Plásticos , Poluentes Químicos da Água/análise
15.
Environ Monit Assess ; 195(1): 164, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36445492

RESUMO

Coastal sediments in the Mong Cai area were collected and analyzed for grain size, heavy metals, total organic carbon, and isotopes (210Pb, 226Ra, δ15N, δ13C) to assess sediment quality. The most common sediments were fine sand in surface sediment, very fine sand in core C1, and very coarse and coarse silt in core C2. The total organic carbon was highest in C2 next to the surface and lowest in C1, with content levels of 1.81%, 0.40%, and 0.31%, respectively. The chronology in C1 was 1877-2019 (142 years, 0-5 0 cm), with an average sedimentation rate of 0.71 cm/year. In C2, the chronology was 1944-2019 (75 years, 0-14 cm), with an average sedimentation rate of 0.27 cm/year. These δ13C and δ15N in the sediment reflect the source of the organic matter mix from the marine and terrigenous sediments. All studied heavy metals were lower than the ISQGs, with the exception of As in C1 and C2, which were higher. C1 showed a decline in As over time, while C2 As levels increased between 1996 and 2019. In terms of heavy metal pollution indexes, the geoaccumulation index (Igeo) showed that C1 and C2 were unpolluted to moderately polluted with As, with Li and Pb in C2; the enrichment factor (EF) was moderately enriched with As; the contamination factor (CF) was moderately contaminated (Pb, Cd, Fe, Mo, and Li) in C2 and C1 (Cd, As, Li) and considerably contaminated (As) in C2. The risk factor (ER) of As showed a moderate potential ecological risk in C2. The degree of contamination (CD) ranged from moderate to considerable (C1, C2), and the ecological risk (RI) was low. Although CD ranged from moderate (C1) to considerable (C2), most contamination was concentrated at the bottom of the cores. RI was low. The Mong Cai sediment quality does not currently affect the coastal area's ecosystem and fauna.


Assuntos
Metais Pesados , Areia , Ecossistema , Chumbo , Vietnã , Monitoramento Ambiental , Carbono
16.
Diabetologia ; 64(4): 923-931, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33483760

RESUMO

AIMS/HYPOTHESIS: Distal diabetic sensorimotor polyneuropathy (DSP) is a common complication of diabetes with many patients showing a reduction of intraepidermal nerve fibre density (IENFD) from skin biopsy, a validated and sensitive diagnostic tool for the assessment of DSP. Axonal swelling ratio is a morphological quantification altered in DSP. It is, however, unclear if axonal swellings are related to diabetes or DSP. The aim of this study was to investigate how axonal swellings in cutaneous nerve fibres are related to type 2 diabetes mellitus, DSP and neuropathic pain in a well-defined cohort of patients diagnosed with type 2 diabetes. METHODS: A total of 249 participants, from the Pain in Neuropathy Study (UK) and the International Diabetic Neuropathy Consortium (Denmark), underwent a structured neurological examination, nerve conduction studies, quantitative sensory testing and skin biopsy. The study included four groups: healthy control study participants without diabetes (n = 45); participants with type 2 diabetes without DSP (DSP-; n = 31); and participants with evidence of DSP (DSP+; n = 173); the last were further separated into painless DSP+ (n = 74) and painful DSP+ (n = 99). Axonal swellings were defined as enlargements on epidermal-penetrating fibres exceeding 1.5 µm in diameter. Axonal swelling ratio is calculated by dividing the number of axonal swellings by the number of intraepidermal nerve fibres. RESULTS: Median (IQR) IENFD (fibres/mm) was: 6.7 (5.2-9.2) for healthy control participants; 6.2 (4.4-7.3) for DSP-; 1.3 (0.5-2.2) for painless DSP+; and 0.84 (0.4-1.6) for painful DSP+. Swelling ratios were calculated for all participants and those with IENFD > 1.0 fibre/mm. When only those participants with IENFD > 1.0 fibre/mm were included, the axonal swelling ratio was higher in participants with type 2 diabetes when compared with healthy control participants (p < 0.001); however, there was no difference between DSP- and painless DSP+ participants, or between painless DSP+ and painful DSP+ participants. The axonal swelling ratio correlated weakly with HbA1c (r = 0.16, p = 0.04), but did not correlate with the Toronto Clinical Scoring System (surrogate measure of DSP severity), BMI or type 2 diabetes duration. CONCLUSIONS/INTERPRETATION: In individuals with type 2 diabetes where IENFD is >1.0 fibre/mm, axonal swelling ratio is related to type 2 diabetes but is not related to DSP or painful DSP. Axonal swellings may be an early marker of sensory nerve injury in type 2 diabetes.


Assuntos
Axônios/patologia , Diabetes Mellitus Tipo 2/patologia , Neuropatias Diabéticas/patologia , Pele/inervação , Idoso , Biópsia , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Medição da Dor , Valor Preditivo dos Testes , Estudos Retrospectivos
17.
Mod Pathol ; 34(1): 194-206, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32724153

RESUMO

TP53 mutations are implicated in the progression of mucinous borderline tumors (MBOT) to mucinous ovarian carcinomas (MOC). Optimized immunohistochemistry (IHC) for TP53 has been established as a proxy for the TP53 mutation status in other ovarian tumor types. We aimed to confirm the ability of TP53 IHC to predict TP53 mutation status in ovarian mucinous tumors and to evaluate the association of TP53 mutation status with survival among patients with MBOT and MOC. Tumor tissue from an initial cohort of 113 women with MBOT/MOC was stained with optimized IHC for TP53 using tissue microarrays (75.2%) or full sections (24.8%) and interpreted using established criteria as normal or abnormal (overexpression, complete absence, or cytoplasmic). Cases were considered concordant if abnormal IHC staining predicted deleterious TP53 mutations. Discordant tissue microarray cases were re-evaluated on full sections and interpretational criteria were refined. The initial cohort was expanded to a total of 165 MBOT and 424 MOC for the examination of the association of survival with TP53 mutation status, assessed either by TP53 IHC and/or sequencing. Initially, 82/113 (72.6%) cases were concordant using the established criteria. Refined criteria for overexpression to account for intratumoral heterogeneity and terminal differentiation improved concordance to 93.8% (106/113). In the expanded cohort, 19.4% (32/165) of MBOT showed evidence for TP53 mutation and this was associated with a higher risk of recurrence, disease-specific death, and all-cause mortality (overall survival: HR = 4.6, 95% CI 1.5-14.3, p = 0.0087). Within MOC, 61.1% (259/424) harbored a TP53 mutation, but this was not associated with survival (overall survival, p = 0.77). TP53 IHC is an accurate proxy for TP53 mutation status with refined interpretation criteria accounting for intratumoral heterogeneity and terminal differentiation in ovarian mucinous tumors. TP53 mutation status is an important biomarker to identify MBOT with a higher risk of mortality.


Assuntos
Biomarcadores Tumorais/genética , Análise Mutacional de DNA , Imuno-Histoquímica , Mutação , Neoplasias Císticas, Mucinosas e Serosas/genética , Neoplasias Ovarianas/genética , Proteína Supressora de Tumor p53/genética , Adulto , Austrália , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Císticas, Mucinosas e Serosas/mortalidade , Neoplasias Císticas, Mucinosas e Serosas/patologia , Neoplasias Císticas, Mucinosas e Serosas/terapia , América do Norte , Variações Dependentes do Observador , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Análise Serial de Tecidos , Reino Unido
18.
Environ Res ; 197: 111158, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33887272

RESUMO

Comprehensive and updated information about polychlorinated biphenyls (PCBs) and brominated flame retardants (BFRs) in surface sediments from Hanoi, the capital city of Vietnam, is rather scarce. In this study, concentrations and profiles of 209 PCBs, 41 polybrominated diphenyl ethers (PBDEs), 2,2',4,4',5,5'-hexabromobiphenyl (BB-153), hexabromocyclododecane (HBCD), pentabromoethylbenzene (PBEB), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), and decabromodiphenyl ethane (DBDPE) were determined in sediment samples collected from the Red River and some inner-city rivers of Hanoi. Concentrations (ng/g dry weight, median and range) of pollutants decreased in the order: DBDPE (28; not detected ND - 59) ≈ PCBs (27; 1.7-50) > PBDEs (23; 0.20-61) > HBCD (1.2; ND - 5.2) > BTBPE (0.46; ND - 3.6) > BB-153 (0.004; ND - 0.014) > PBEB (ND). Pollutant levels in the inner-city river sediments were about one to two orders of magnitude higher than those measured in the Red River main stream sediments. Tri-to hexa-CBs are major homologs but detailed profiles vary between individual samples, reflecting source and/or seasonal variations. CB-11 and CB-209 were found at higher proportions in sediments than in technical PCB mixtures, suggesting their novel sources from pigments. Deca-BDE and DBDPE are the most predominant BFRs with an increasing trend predicted for DBDPE. A preliminary ecological risk assessment was conducted for these pollutants in sediments. Total PCBs and deca-BDE in a few inner-city river sediments may exhibit adverse effects on benthic organisms, but no serious risk was estimated in general.


Assuntos
Retardadores de Chama , Bifenilos Policlorados , Monitoramento Ambiental , Retardadores de Chama/análise , Éteres Difenil Halogenados/análise , Vietnã
19.
Sensors (Basel) ; 21(3)2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33499320

RESUMO

Underwater vehicles (UVs) are subjected to various environmental disturbances due to ocean currents, propulsion systems, and un-modeled disturbances. In practice, it is very challenging to design a control system to maintain UVs stayed at the desired static position permanently under these conditions. Therefore, in this study, a nonlinear dynamics and robust positioning control of the over-actuated autonomous underwater vehicle (AUV) under the effects of ocean current and model uncertainties are presented. First, a motion equation of the over-actuated AUV under the effects of ocean current disturbances is established, and a trajectory generation of the over-actuated AUV heading angle is constructed based on the line of sight (LOS) algorithm. Second, a dynamic positioning (DP) control system based on motion control and an allocation control is proposed. For this, motion control of the over-actuated AUV based on the dynamic sliding mode control (DSMC) theory is adopted to improve the system robustness under the effects of the ocean current and model uncertainties. In addition, the stability of the system is proved based on Lyapunov criteria. Then, using the generalized forces generated from the motion control module, two different methods for optimal allocation control module: the least square (LS) method and quadratic programming (QP) method are developed to distribute a proper thrust to each thruster of the over-actuated AUV. Simulation studies are conducted to examine the effectiveness and robustness of the proposed DP controller. The results show that the proposed DP controller using the QP algorithm provides higher stability with smaller steady-state error and stronger robustness.

20.
Bull Environ Contam Toxicol ; 107(3): 475-486, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33760936

RESUMO

Unsubstituted and methylated polycyclic aromatic hydrocarbons (22 PAHs and 17 Me-PAHs) were examined in surface sediments collected from the Red River and four inner-city rivers of Hanoi City, Vietnam. Concentrations of total PAHs and Me-PAHs ranged from 52 to 920 (median 710) and from 70 to 2600 (median 1000) ng/g dry weight in samples of dry and wet seasons, respectively. Significant correlation was observed between total PAHs and organic carbon contents (Spearman's ρ = 0.782; p < 0.05). PAHs were more abundant than Me-PAHs in all samples and dominated by 4-6 ring compounds. The most predominant PAHs were benzo[ghi]perylene, benzo[b/j]fluoranthene, chrysene, pyrene, fluoranthene, and phenanthrene. Methylated derivatives of naphthalene, phenanthrene, anthracene, and benz[a]anthracene were frequently detected. The patterns of PAHs indicated principal pyrogenic sources (notably gasoline exhaust) in this highly urbanized area. The occurrence of several PAHs were occasionally associated with adverse effects on benthic organisms of the inner-city rivers.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Monitoramento Ambiental , Sedimentos Geológicos , Hidrocarbonetos Policíclicos Aromáticos/análise , Medição de Risco , Vietnã , Poluentes Químicos da Água/análise
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