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1.
BMC Cancer ; 21(1): 45, 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33422027

RESUMO

BACKGROUND: Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome. Comparison of prognosis between LS and sporadic CRC (SCRC) were rare, with conflicting results. This study aimed to compare the long-term outcomes between patients with LS and SCRC. METHODS: Between June 2008 and September 2018, a total of 47 patients were diagnosed with LS by genetic testing at Fudan University Shanghai Cancer Center. A 1:2 propensity score matching was performed to obtain homogeneous cohorts from SCRC group. Thereafter, 94 SCRC patients were enrolled as control group. All of enrolled patients received curative surgeries and standardized postoperative monitoring. The long-term survival rates between the two groups were compared, and the prognostic factors were also analyzed. RESULTS: The 5-year overall survival rate of LS group was 97.6%, which was significantly higher than of 82.6% for SCRC group (χ2 = 4.745, p = 0.029). The 5-year recurrence free survival rate showed no significant differences between the two groups (78.0% for LS group vs. 70.6% for SCRC patients; χ2 = 1.260, p = 0.262). The 5-year tumor free survival rates in LS group was 62.1% for LS patients, which were significantly lower than of 70.6% for SCRC group (χ2 = 4.258, p = 0.039). Subgroup analysis of recurrent patients show that the LS group had longer overall survival than the SCRC group after combined chemotherapy. By multivariate analysis, we found that tumor recurrence of primary CRC [Risk ratio (95% (confidence interval): 48.917(9.866-242.539); p < 0.001] and late TNM staging [Risk ratio (95% (confidence interval): 2.968(1.478-5.964); p = 0.002] were independent risk factors for OS. CONCLUSION: LS patients have better long-term survival prognosis than SCRC patients, even though the two groups have statistically comparable recurrence free survival. Combined chemotherapy is an effective treatment for LS patients who developed primary CRC recurrence. Standardized postoperative monitoring for LS patients may enable detection of metachronous tumors at earlier stages, which was a guarantee of a favorable prognosis despite lower tumor free survival.

2.
Bone ; 144: 115806, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33333245

RESUMO

Substance P (SP) is a sensory neuropeptide that is expressed by the neurons innervating bone. There is considerable evidence that SP can regulate bone cell function in vitro, but it is unclear whether SP modulates bone modeling or remodeling in vivo. To answer this question we characterized the bone phenotype of mice with deletion of the Tac1 gene expressing SP. The phenotypes of 2-month-old and 5-month-old SP deficient mice and their wildtype controls were characterized by using µCT imaging, static and dynamic bone histomorphometry, and urinary deoxypyridinoline cross-links (DPD) measurement. No differences in bone phenotypes were observed between the 2 strains at 2 months of age. By 5 months both the wildtype and SP deficient mice had developed cancellous osteopenia, but relative to the wild-type mice the SP deficient mice had significantly greater cancellous bone loss. The SP deficient mice also exhibited decreased bone formation, increased osteoclast number, and increased urinary DPD levels. Cortical defect early repair was delayed in 5-month-old mice lacking SP. Collectively, these findings indicate that SP signaling is not required for bone modeling, but SP signaling reduces age-related osteopenia and accelerates cortical defect reparation, data supporting the hypothesis that SP is an anabolic physiologic regulator of bone metabolism.

3.
J Environ Manage ; 280: 111710, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33308931

RESUMO

Reducing harmful algal blooms in Lake Erie, situated between the United States and Canada, requires implementing best management practices to decrease nutrient loading from upstream sources. Bi-national water quality targets have been set for total and dissolved phosphorus loads, with the ultimate goal of reaching these targets in 9-out-of-10 years. Row crop agriculture dominates the land use in the Western Lake Erie Basin thus requiring efforts to mitigate nutrient loads from agricultural systems. To determine the types and extent of agricultural management practices needed to reach the water quality goals, we used five independently developed Soil and Water Assessment Tool models to evaluate the effects of 18 management scenarios over a 10-year period on nutrient export. Guidance from a stakeholder group was provided throughout the project, and resulted in improved data, development of realistic scenarios, and expanded outreach. Subsurface placement of phosphorus fertilizers, cover crops, riparian buffers, and wetlands were among the most effective management options. But, only in one realistic scenario did a majority (3/5) of the models predict that the total phosphorus loading target would be met in 9-out-of-10 years. Further, the dissolved phosphorus loading target was predicted to meet the 9-out-of-10-year goal by only one model and only in three scenarios. In all scenarios evaluated, the 9-out-of-10-year goal was not met based on the average of model predictions. Ensemble modeling revealed general agreement about the effects of several practices although some scenarios resulted in a wide range of uncertainty. Overall, our results demonstrate that there are multiple pathways to approach the established water quality goals, but greater adoption rates of practices than those tested here will likely be needed to attain the management targets.


Assuntos
Monitoramento Ambiental , Lagos , Agricultura , Canadá , Eutrofização , Fósforo/análise , Qualidade da Água
4.
J Environ Manage ; 279: 111708, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33370707

RESUMO

This research examines public acceptability of regulations to reduce agricultural nutrient runoff and curb Harmful Algal Blooms (HABs). We tested the effects of two novel policy specific beliefs including support for farmers' autonomy and support for external accountability. We also simultaneously tested the direct and indirect effects of political orientation and environmental worldview through a Direct Effect Model and a Mediation Model using structural equation modelling. Survey data were collected from 729 Ohio residents collected in November 2018. The specific regulatory policy measure we targeted is fines on excessive agricultural runoff. As hypothesized, autonomy beliefs negatively affect, and accountability positively affect support for fines. Both models revealed good fits. the direct effects of environmental worldviews political orientation were not supported. Instead, environmental worldviews indirectly increased support for fines through increased accountability beliefs and diminished autonomy beliefs. From the results, we suggest that when proposing suitable regulations for specific sites, policy makers and interest groups should be aware of differences in public support for farmer autonomy and external accountability, and that such differences are likely rooted in environmental worldviews. The study also suggests a need for coupled ecological and social studies that assess the likelihood of regional agricultural producers voluntarily adopting conservation practices and forecast the effectiveness of potential accountability measures.


Assuntos
Agricultura , Fazendeiros , Humanos , Nutrientes , Ohio , Políticas
5.
Biomaterials ; 266: 120430, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33011679

RESUMO

Immunogenic photodynamic therapy (PDT) has the potential to moderate the shortfalls of cancer immunotherapy. However, its efficacy is severely limited particularly because of the lack of optimal photosensitizers and smart delivery processes and the inherent shortcomings of PDT (e.g., hypoxia resistance). Here, we demonstrate a clinically promising approach that utilizes a water-soluble phthalocyanine derivative (PcN4) concomitantly delivered with a hypoxia-activated prodrug (AQ4N) to amplify the effect of PDT and enhance cancer immunotherapy. After intravenous injection, PcN4 selectively interacted with endogenous albumin dimers and formed supramolecular complexes, providing a facile and green approach for tumor-targeted PDT. The concomitant delivery of AQ4N overcame the limitations of hypoxia in PDT and improved the antitumor activity of PDT. Treatment with PcN4-mediated and AQ4N-amplified PDT almost completely eradicated sizable primary tumors in a triple-negative breast cancer model and significantly activated CD8+ T cells. As the majority of tumor infiltrating CD8+ T cells were both PD-1- and TIM3-positive, additional combination therapy using PD-L1/PD-1 pathway blockade was warranted. After combination with immune checkpoint blockade treatment, an enhanced abscopal effect was achieved in both distant and metastatic tumors.

6.
Environ Sci Technol ; 2020 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-33283499

RESUMO

Extreme precipitation events affect water quantity and quality in various regions of the world. Heavy precipitation in 2019 resulted in a record high area of unplanted agricultural fields in the U.S. and especially in the Maumee River Watershed (MRW). March-July phosphorus (P) loads from the MRW drive harmful algal bloom (HAB) severity in Lake Erie; hence changes in management that influence P export can ultimately affect HAB severity. In this study, we found that the 2019 dissolved reactive P (DRP) load from March-July was 29% lower than predicted, while the particulate P (PP) load was similar to the predicted value. Furthermore, the reduced DRP load resulted in a less severe HAB than predicted based on discharge volume. The 29% reduction in DRP loss in the MRW occurred with a 62% reduction in applied P, emphasizing the strong influence of recently applied P and subsequent incidental P losses on watershed P loading. Other possible contributing factors to this reduced load include lower precipitation intensity, altered tillage practices, and effects of fallow soils, but more data is needed to assess their importance. We recommend conservation practices focusing on P application techniques and timing and improving resiliency against extreme precipitation events.

7.
Asian J Surg ; 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33288372

RESUMO

Minimally invasive surgery includes traditional laparoscopic and robot-assisted surgery. Although many studies related to robotic surgery and laparoscopic surgery have been published, when doing our search, scientometric studies that focus on related robotic surgery versus laparoscopic surgery were limited. In this study, we aimed to analyze and review the research hots and research status of robotic surgery versus laparoscopic surgery. We searched publications that involved robotic surgery versus laparoscopic surgery in the Web of Science database from 1980 to May 23, 2020. The top 100 publications were published in 2012 with the number of 17 and citations ranged from 618 to 64. Published across 34 different journals, namely European urology (n = 17) and others, the greatest contribution among 36 institutes was made by the Cleveland Clinic (n = 11). Of the top 100 publications, a total of 429 unique words were identified and the most frequently occurring keyword was laparoscopy (n = 33). The co-occurrence of keywords in the top 100 publications indicated that the study of diseases mainly focused on prostatectomy, complications, prostate cancer, retropubic prostatectomy, nephron-sparing surgery, lymph-node dissection, total mesenteric excision, sexual function, rectal cancer, and assisted distal gastrectomy. In recent years, comparative research on robot and laparoscopic surgery has decreased and most studies focus on cancer.

8.
Pain ; 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33259455

RESUMO

It has been proposed that Complex Regional Pain Syndrome (CRPS) is a post-traumatic autoimmune disease. Previously we observed that B cells contribute to CRPS-like changes in a mouse tibia fracture model, and that early (< 12 months duration) CRPS patient IgM antibodies have pronociceptive effects in the skin and spinal cord of muMT fracture mice lacking B cells. The current study evaluated the pronociceptive effects of intraplantar or intrathecal injections of early CRPS IgM (5ug) in muMT fracture mice. Skin and lumbar spinal cord were collected for immunohistochemistry and polymerase chain reaction (PCR) analyses. Wildtype mice exhibited post fracture increases in complement component C5a and its receptor expression in skin and spinal cord, predominantly on dermal macrophages and spinal microglia. Intraplantar IgM injection caused nociceptive sensitization in muMT fracture mice with increased complement component C1q and inflammatory cytokine expression, and these IgM effects were blocked by a C5a receptor antagonist (PMX53) or a global cytokine inhibitor (pentoxifylline). Intrathecal IgM injection also had pronociceptive effects with increased spinal cytokine expression, effects that were blocked by PMX53 or pentoxifylline treatment. Intrathecal injection of chronic (> 12 months duration) CRPS patient IgM (but not IgG) caused nociceptive sensitization in muMT fracture mice, but intraplantar injection of chronic CRPS IgM or IgG had no effect. We postulate that CRPS IgM antibodies bind to neoantigens in the fracture limb skin and corresponding spinal cord to activate C5a complement signaling in macrophages and microglia, evoking proinflammatory cytokine expression contributing to nociceptive sensitization in the injured limb.

9.
BMC Gastroenterol ; 20(1): 415, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33302876

RESUMO

BACKGROUND: This study explored the prognostic significance of Glypican (GPC) family genes in patients with pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). METHODS: A total of 112 PDAC patients from TCGA and 48 patients from GEO were included in the analysis. The relationship between overall survival and the expression of GPC family genes as well as basic clinical characteristics was analyzed using the Kaplan-Meier method with the log-rank test. Joint effects survival analysis was performed to further examine the relationship between GPC genes and prognosis. A prognosis nomogram was established based on clinical characteristics and prognosis-related genes. Prognosis-related genes were investigated by genome-wide co-expression analysis and gene set enrichment analysis (GSEA) was carried out to identify potential mechanisms of these genes affecting prognosis. RESULTS: In TCGA database, high expression of GPC2, GPC3, and GPC5 was significantly associated with favorable survival (log-rank P = 0.031, 0.021, and 0.028, respectively; adjusted P value = 0.005, 0.022, and 0.020, respectively), and joint effects analysis of these genes was effective for prognosis prediction. The prognosis nomogram was applied to predict the survival probability using the total scores calculated. Genome-wide co-expression and GSEA analysis suggested that the GPC2 may affect prognosis through sequence-specific DNA binding, protein transport, cell differentiation and oncogenic signatures (KRAS, RAF, STK33, and VEGFA). GPC3 may be related to cell adhesion, angiogenesis, inflammatory response, signaling pathways like Ras, Rap1, PI3K-Akt, chemokine, GPCR, and signatures like cyclin D1, p53, PTEN. GPC5 may be involved in transcription factor complex, TFRC1, oncogenic signatures (HOXA9 and BMI1), gene methylation, phospholipid metabolic process, glycerophospholipid metabolism, cell cycle, and EGFR pathway. CONCLUSION: GPC2, GPC3, and GPC5 expression may serve as prognostic indicators in PDAC, and combination of these genes showed a higher efficiency for prognosis prediction.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33159544

RESUMO

To study the difference in transcriptome level of fatty acid metabolism pathway in Bamei pork and the difference of pork quality caused by the difference. In this study, Bamei pigs breeding in Huzhu farm of QingHai province were selected as the test object, compared with Gansu Black pigs. Four indexes of nutmeg acid (DX1), palmitic acid (DX2), stearic acid (DX3) and linoleic acid (DX4) were set. The expression profiles of fat metabolism related genes between the two groups samples were analysed by GCMS metabolomics and transcriptomics, then coexpression network analysis were conducted to obtain phenotypic related genes. The results showed that the metabolic levels of DX3 and DX4 were significantly higher than those of other fatty acids. Among these differences, the ENSSSCG00000024681 (G1) and ENSSSCG00000036883 (G2) genes play important regulatory roles in fatty acid metabolism, and the upregulated expression of their gene obviously affects the level of fatty acid metabolism, thereby affecting the quality and taste of pork. In addition, we found that there was a good correlation between the same lines, and the genetic traits of the hybrid lines of Bamei pig and Black pig are more inclined to Bamei pig. In the independent fatty acid metabolism, "Mg2+"and flavin adenine dinucleotide are more active, which plays an important role in energy utilization. Therefore, we can be inferred that the metabolism of stearic acid and linoleic acid are important fatty acids for pork quality. It also further confirms that the research method of combined omics is of great significance for the study of species traits and gene functions.

11.
J Environ Manage ; : 111506, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33168300

RESUMO

Watershed-scale hydrologic models are frequently used to inform conservation and restoration efforts by identifying critical source areas (CSAs; alternatively 'hotspots'), defined as areas that export relatively greater quantities of nutrients and sediment. The CSAs can then be prioritized or 'targeted' for conservation and restoration to ensure efficient use of limited resources. However, CSA simulations from watershed-scale hydrologic models may be uncertain and it is critical that the extent and implications of this uncertainty be conveyed to stakeholders and decision makers. We used an ensemble of four independently developed Soil and Water Assessment Tool (SWAT) models and a SPAtially Referenced Regression On Watershed attributes (SPARROW) model to simulate CSA locations for flow, phosphorus, nitrogen, and sediment within the ~17,000-km2 Maumee River watershed at the HUC-12 scale. We then assessed uncertainty in CSA simulations determined as the variation in CSA locations across the models. Our application of an ensemble of models - differing with respect to inputs, structure, and parameterization - facilitated an improved accounting of CSA prediction uncertainty. We found that the models agreed on the location of a subset of CSAs, and that these locations may be targeted with relative confidence. However, models more often disagreed on CSA locations. On average, only 16%-46% of HUC-12 subwatersheds simulated as a CSA by one model were also simulated as a CSA by a different model. Our work shows that simulated CSA locations are highly uncertain and may vary substantially across models. Hence, while models may be useful in informing conservation and restoration planning, their application to identify CSA locations would benefit from comprehensive uncertainty analyses to avoid inefficient use of limited resources.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33072620

RESUMO

Thyroxine metabolism is an important topic of pathogenesis research and treatment schedule of subclinical hypothyroidism (SCH). L-Thyroxine replacement therapy (LRT) is usually recommended for severe SCH patients only. Our previous studies reported that disordered serum lipid of mild SCH people could also benefit from LRT. However, the benefits were different among individuals, as shown by the variations in drug dosage that required to maintain thyroid-stimulating hormone (TSH) stability. Alternative pathways, such as sulfation and glucuronidation of iodothyronine, may play a role in thyroid hormones metabolism in peripheral tissues aside from thyroid. Conjugated thyroxine can be hydrolyzed and reused in tissues including gastrointestinal tract, in which gut microbiota are one of the most attractive physiological components. On this site, the roles of gut microbiota in thyroidal metabolism should be valued. In this study, a cross-sectional study was performed by analyzing 16S rDNA of gut microbiota in mild SCH patients treated with L-thyroxine or not. Subjects were divided by serum lipid level, L-thyroxine treatment, or L-thyroxine dosage, respectively. Relationship between gut microbiome and serum profile, L-thyroxine treatment, and dose were discussed. Other metabolic disorders such as type 2 diabetes and hypertension were also taken into consideration. It turned out that microbiome varied among individuals divided by dose and the increment of L-thyroxine but not by serum lipid profile. Relative abundance of certain species that were associated with thyroxine metabolism were found varied among different L-thyroxine doses although in relatively low abundance. Moreover, serum cholesterol may perform relevance effects with L-thyroxine in shaping microbiome. Our findings suggested that the differences in L-thyroxine dosage required to maintain TSH level stability, as well as the SCH development, which was displayed by the increased L-thyroxine doses in subsequent follow-up, had relationship with gut microbial composition. The reason may due to the differences in thyroxine metabolic capacity in gut. In addition, the metabolic similarity of iodothyronines and bile acid in gut also provides possibilities for the correlation between host's thyroxine and cholesterol levels. This study was registered with ClinicalTrials.gov as number NCT01848171.

13.
Onco Targets Ther ; 13: 9389-9405, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061426

RESUMO

Background: This study was mainly to explore and study the potential application of lipoxygenases (ALOX) family genes in the diagnostic and prognostic values of colon adenocarcinoma (COAD). Methods: Data sets related to the ALOX genes of COAD were obtained from The Cancer Genome Atlas and the University of California, Santa Cruz Xena browser. Then, the relevant biological information was downloaded from the public data platform. Finally, the bioinformatics technologies and clinical verification were employed to comprehensively analyze the potential values of ALOX genes. Results: The Pearson correlation analysis indicated that there were correlations among ALOXE3, ALOX5, ALOX12, and ALOX12B. The diagnostic receiver operating characteristic (ROC) curves suggested that ALOXE3 and ALOX12 had significant diagnosis in COAD: ALOXE3; P<0.001, area under curve (AUC) 95%CI:=0.818 (0.773-0.862) and ALOX12; P<0.001, AUC 95%CI=0.774 (0.682-0.807). Besides, the verification study indicated that ALOX12 had a diagnostic value in COAD. Finally, our multivariate survival analysis and comprehensive prognosis of ALOX genes in COAD suggested that the ALOXE3 and ALOX12 were associated with COAD overall survival: ALOXE3; P=0.025, HR 95%CI=1.765 (1.074-2.901), ALOX12; P=0.046, HR 95%CI=1.680 (1.009-2.796), and the low expression of ALOXE3 and ALOX12 had a favorable prognosis of COAD (all P<0.05); on the contrary, the high regulation of them increased the risk of death. Conclusion: In our study, we observed that the mRNA expressions of ALOX genes were associated with the diagnosis and prognosis of COAD. The results of the diagnostic analysis suggested that ALOX12 might have a diagnosis value in COAD. Besides, our comprehensive prognosis analysis indicated that ALOXE3 combined ALOX12 might serve as potential prognosis biomarkers for COAD.

14.
Opt Lett ; 45(19): 5472-5475, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001922

RESUMO

Inducing and controlling temperature gradients in illuminated subwavelength plasmonic structures is a challenging task. Here, we present a strategy to remotely induce and tune temperature gradients in a subwavelength metallic nanocone by adjusting the angle of incidence of linearly polarized continuous-wave illumination. We demonstrate, through rigorous three-dimensional numerical simulations, that properly tilting the incident illumination angle can increase or decrease the photoinduced temperature gradients within the nanostructure. We analyze the apex-base photoinduced temperature gradient for different illumination directions, resembling typical illumination schemes utilized in surface or tip-enhanced Raman spectroscopy.

15.
Int J Endocrinol ; 2020: 9501826, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33014047

RESUMO

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) and hyperlipidemia (HL) are common metabolic disorders due to overnutrition and obesity. NAFLD is often associated with hyperlipidemia. The aim of this study was to identify and compare the erythrocyte membrane lipids profile in NAFLD patients with or without HL. Methods. A total of 112 subjects (with similar age and body mass index) were divided into four groups: (1) normal controls, (2) NAFLD alone, (3) HL alone, and (4) NAFLD combined with HL (NAFLD + HL). Lipid was extracted from the erythrocyte membrane, and lipid profiles of subjects were analyzed by liquid chromatography mass spectrometry (LC-MS). Results. Data sets from 103 subjects were adopted for lipidomic analysis. Significant changes of lipid species were observed in patient groups, especially in the HL group and NAFLD + HL group. The HL group showed increased level of most lipid species, and decreased level of most lipid species was observed in the NAFLD + HL group. The weight percent of myristic acid, stearic acid, erucic acid, and docosahexaenoic acid also showed distinct variation between different groups. Conclusions. NAFLD, HL, and NAFLD + HL all had an impact on lipid profiling of the erythrocyte membrane. The influence of NAFLD alone is less important compared with HL. Some lipids should be highlighted because of their specific role in cell function and systemic metabolism.

16.
Cancer Sci ; 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32888357

RESUMO

Ribosome assembly factor URB1 is essential for ribosome biogenesis. However, its latent role in cancer remains unclear. Analysis of The Cancer Genome Atlas database and clinical tissue microarray staining showed that URB1 expression was upregulated in colorectal cancer (CRC) and prominently related to clinicopathological characteristics. Silencing of URB1 hampered human CRC cell proliferation and growth in vitro and in vivo. Microarray screening, ingenuity pathway analysis, and JASPAR assessment indicated that activating transcription factor 4 (ATF4) and X-box binding protein 1 (XBP1) are potential downstream targets of URB1 and could transcriptionally interact through direct binding. Silencing of URB1 significantly decreased ATF4 and cyclin A2 (CCNA2) expression in vivo and in vitro. Restoration of ATF4 effectively reversed the malignant proliferation phenotype of URB1-silenced CRC cells. Dual-luciferase reporter and ChIP assays indicated that XBP1 transcriptionally activated ATF4 by binding with its promoter region. X-box binding protein 1 colocalized with ATF4 in the nuclei of RKO cells, and ATF4 mRNA expression was positively regulated by XBP1. This study shows that URB1 contributes to oncogenesis and CRC growth through XBP1-mediated transcriptional activation of ATF4. Therefore, URB1 could be a potential therapeutic target for CRC.

17.
Environ Manage ; 66(5): 733-741, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32964245

RESUMO

Engaging the public in protecting water resources is a critical yet challenging task. A wealth of social science studies has identified psychological predictors for individual pro-environmental behaviors. These predictors can guide communication in public engagement and inform the allocation of engagement efforts. However, a thorny challenge is to select influential factors among many candidates. This paper addresses this challenge by using social science research to guide the development of strategies to motivate the public to protect the North American Great Lakes. We considered a variable selection technique, the LASSO regression, in the post-hoc analysis of the International Joint Commission's 2018 Binational Great Lakes Binational Poll data. The poll surveyed 4250 Canadian and U.S. residents of the Great Lakes basin. We fit LASSO logistic models to predict respondents' intentions to take three public actions to protect the Great Lakes, including contacting public officials, attending public meetings, and engaging in online forums and groups. The models included 41 predictors encompassing demographic characteristics as well as respondents' awareness, beliefs, and values that are pertinent to Great Lakes policy development and management. Results revealed eight variables that consistently predicted the three public actions, including indigenous status, political ideology, impacts of the specific policy issues of nuclear wastes, policy awareness and interests, and the Great Lakes values for personal benefits and wildlife. Based on these findings, we recommend strategies to motivate the public to take public actions to protect the Great Lakes.

18.
Front Oncol ; 10: 1603, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32984025

RESUMO

Objective: This study aimed to compare the molecular, clinical, and pathological characteristics and pedigrees of familial colorectal cancer type X (FCCTX) with those of Lynch syndrome (LS) to provide a theoretical basis for the management of FCCTX. Methods: Overall, 46 cases of FCCTX and 47 LS probands and affected families were enrolled between June 2008 and September 2018 for this study. Multigene cancer panel tests that included 139 genes were performed for all patients, and variants in each group were described. The clinical, pathological, and pedigree characteristics were also compared between the two groups. Results: In total, 42 variants were detected in 27 (58.7%) cases in the FCCTX group, with BRCA1, BRCA2, POLE, POLD1, ATR, and ATM being the most frequently mutated genes. The mean onset age of colorectal cancer (CRC) was significantly older in the FCCTX group than in the LS group (53.57 ± 12.88 years vs. 44.36 ± 11.26 years, t = -9.204, p < 0.001). The proportion of patients with rectal cancer was also higher in the FCCTX group than in the LS group [43.5% (20/46) vs. 10.6% (5/47), χ2 = 12.823, p = 0.005]. Within a median follow-up time of 53.9 ± 37.0 months, the proportion of patients who developed metachronous CRC was significantly higher in the LS group than in the FCCTX group [34.0% (16/47) vs. 13.0% (6/46), χ2 = 5.676, p = 0.017]. When comparing pedigrees, older age at cancer onset and rectal cancer clustering were observed in the FCCTX families. A higher prevalence in male patients was also observed in the FCCTX families. Conclusion: FCCTX is an entity distinct from LS, but its genetic etiology remains unknown. A larger multigene panel would be recommended for determining the underlying pathogenic variants. Considering the pathology and moderate penetrance of the CRC link to FCCTX, less stringent surgical treatments and colonoscopy surveillance would be preferable. Rectum preference is a typical feature of FCCTX. Colonoscopy surveillance in FCCTX families could be less intensive, and more attention should be given to male members.

19.
Front Genet ; 11: 991, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973888

RESUMO

In this study, we compared the molecular, clinical, and pathological characteristics, as well as pedigrees, between patients with Lynch-like syndrome (LLS) and confirmed Lynch syndrome (LS) to develop appropriate management strategies for patients with LLS and their affected family members. Between June 2008 and September 2018, 81 patients with LLS and 47 patients with LS who developed colorectal cancer (CRC) were enrolled in this study. Multigene panel testing included 139 genes and was performed for all patients. The variants identified in each group were described, and clinicopathological characteristics and pedigrees were compared between the two groups. In the LLS group, a total of 52 variants were detected in 44 (54.3%) patients. Among the 52 variants, 17 were variants of unknown significance in mismatch repair genes, and the other most frequently mutated genes were MUYTH, POLE, BRCA2, and GJB2. The proportion of early-onset patients was significantly higher among the LS probands than among the LLS probands (74.5 and 53.1%, respectively; χ2 = 5.712, P = 0.017). On the other hand, the proportion of primary CRC developed in the rectum was higher in the LLS group than in the LS group (25.9 and 10.6%, respectively; χ2 = 2.358, P = 0.046). There were no significant differences in the occurrence of metachronous CRC (P = 0.632) and extra-colorectal cancer (extra-CRC) (P = 0.145) between the two groups. However, analysis of pedigrees showed that more patients developed CRC in the LS families (P = 0.013), whereas more patients with extra-CRC were observed in the LLS families (P = 0.045). A higher prevalence of male patients was observed in the LLS families (P = 0.036). In conclusion, LLS should be classified as a mixed entity, containing cases of LS, other hereditary cancer syndromes, and sporadic CRC. The high risks of CRC and extra-CRCs, which were found in this study, suggest tailored management policy and surveillance should be formulated based on individual and family risk. The surveillance regimen can be based on the presence of confirmed pathogenic/likely pathogenic germline variant(s) and family history.

20.
Hortic Res ; 7: 149, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922821

RESUMO

Downy mildew of grapevine (Vitis vinifera L.), caused by the oomycete pathogen Plasmopara viticola, is one of the most serious concerns for grape production worldwide. It has been widely reported that the pathogenesis-related 4 (PR4) protein plays important roles in plant resistance to diseases. However, little is known about the role of PR4 in the defense of grapevine against P. viticola. In this study, we engineered loss-of-function mutations in the VvPR4b gene from the cultivar "Thompson Seedless" using the CRISPR/Cas9 system and evaluated the consequences for downy mildew resistance. Sequencing results showed that deletions were the main type of mutation introduced and that no off-target events occurred. Infection assays using leaf discs showed that, compared to wild-type plants, the VvPR4b knockout lines had increased susceptibility to P. viticola. This was accompanied by reduced accumulation of reactive oxygen species around stomata. Measurement of the relative genomic abundance of P. viticola in VvPR4b knockout lines also demonstrated that the mutants had increased susceptibility to the pathogen. Our results confirm that VvPR4b plays an active role in the defense of grapevine against downy mildew.

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