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1.
Insect Mol Biol ; 29(4): 353-362, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32086963

RESUMO

RNA interference (RNAi), one of the strategies that organisms use to defend against invading viruses, is an important tool for functional genomic analysis. In insects, the efficacy of RNAi varies amongst taxa. Lepidopteran insects are, in large part, recalcitrant to RNAi. The overall goal of this study is to overcome such insensitivity in lepidopterans to RNAi. We hypothesize that over-expression of core RNAi machinery enzymes can improve RNAi efficacy in traditionally recalcitrant species. A transgenic Bombyx mori strain, Baculovirus Immediate-Early Gene, ie1, promoter driven expression of silkworm Dicer2 coding sequence (IE1-BmDicer2), which over-expresses BmDicer2, was generated by piggyBac transposon-mediated transgenesis. Two indexes, the ratio of animals that showed a silencing phenotype and the duration of silencing, were used to evaluate silencing efficiency. Significant knockdown of target gene expression was observed at 48 h postinjection at both the transcriptional and translational levels. Furthermore, we coexpressed B. mori Argonaute 2 BmAgo2)and BmDicer 2 and found that 22% of the animals (n = 18) showed an obvious silencing effect even at 72 h, suggesting that coexpression of these two RNAi core machinery enzymes further increased the susceptibility of B. mori to injected double-stranded RNAs. This study offers a new strategy for functional genomics research in RNAi-refractory insect taxa in general and for lepidopterans in particular.


Assuntos
Bombyx/genética , Regulação da Expressão Gênica , Larva/genética , Interferência de RNA , Animais , Animais Geneticamente Modificados/genética , Animais Geneticamente Modificados/crescimento & desenvolvimento , Animais Geneticamente Modificados/metabolismo , Bombyx/crescimento & desenvolvimento , Bombyx/metabolismo , Larva/crescimento & desenvolvimento , Larva/metabolismo
2.
Clin Radiol ; 75(12): 921-926, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32782129

RESUMO

AIM: To determine if there is an association between area-based visceral abdominal adipose tissue (VAT), subcutaneous abdominal adipose tissue (SAT), and abdominal circumference measured on computed tomography (CT) angiography before trans-catheter aortic valve replacement (TAVR) and post-TAVR acute kidney injury (AKI). MATERIALS AND METHODS: In this retrospective cohort study of 106 TAVR patients, SAT and VAT areas and abdominal circumference was measured on a single CT section at L4 vertebral level. Univariate comparisons between patients who did and did not develop AKI were undertaken for radiological measurements. Multivariable logistic regression was used to assess association between CT measurements and the development of post-TAVR AKI. RESULTS: Post-TAVR AKI occurred in 20 of 106 patients (19%). In univariate comparisons, body mass index (BMI) did not differ significantly between patients who did and did not develop AKI (p=0.14); however, VAT+SAT (443.2±163.7 versus 351±168.7 cm2; p=0.03), VAT (213.9±110.6 versus 153.9±96.1 cm2; p=0.03), and outer abdominal circumference (100.2±14.4 cm versus 91.8±13.3 cm; p=0.02) were significantly higher in the patients who did not develop post-TAVR AKI. These three measures on pre-TAVR CT angiogram remained significantly associated with reduced post-TAVR AKI with a lower incidence of post-TAVR AKI after multivariable adjustment for pre-TAVR estimated glomerular filtration rate and patient height (p<0.05). CONCLUSION: This study found that increased abdominal obesity as assessed by measures on pre-TAVR CT angiogram is associated with a significantly lower incidence of AKI.


Assuntos
Injúria Renal Aguda/epidemiologia , Angiografia por Tomografia Computadorizada , Obesidade Abdominal/diagnóstico por imagem , Complicações Pós-Operatórias/epidemiologia , Substituição da Valva Aórtica Transcateter , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Estudos Retrospectivos , Fatores de Risco
3.
HIV Med ; 19(2): 143-151, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29110385

RESUMO

OBJECTIVES: Based on a growing body of evidence implicating low vitamin D status in the development of cardiovascular disease (CVD), we hypothesized that in Canadian HIV-positive adults, low 25-hydroxyvitamin D (25(OH)D) concentration would be associated with increased subclinical vascular disease progression. METHODS: We prospectively studied the relationship between baseline 25(OH)D and subsequent progression of carotid intima-media thickness (CIMT) between 2002 and 2011, in the Canadian HIV Vascular Study using stored blood specimens. RESULTS: Of the 128 participants, 89.1% were men, the mean age (standard deviation [SD]) was 46.5 (8.2) years, 93.8% were white, and 36.7% were current smokers. Mean (SD) annual CIMT follow-up was 5.9 (1.8) years (maximum 8.5 years), providing approximately 750 patient-years of follow-up. Mean (SD) CIMT progression was 0.027 (0.030) mm/year. Mean (SD) 25(OH)D was 95.0 (46.9) nmol/L. Only 13.3% of participants were vitamin D deficient (25(OH)D < 50 nmol/L), whereas 61.7% had a 25(OH)D exceeding the sufficiency threshold (75 nmol/L). Vitamin D quartiles were inversely associated with body mass index (BMI) (P = 0.034), total cholesterol to high-density lipoprotein (HDL) cholesterol ratio (P = 0.001) and parathyroid hormone concentration (P = 0.003), but not efavirenz exposure (P = 0.141). In linear regression analyses, baseline 25(OH)D as a continuous variable was inversely associated with CIMT progression in univariable (P < 0.001) and multivariable (P < 0.001) models. CONCLUSIONS: Baseline 25(OH)D was associated with CIMT progression in this relatively vitamin D replete, predominately white and male, Canadian HIV-positive population. Future research needs to establish causality as this may warrant more targeted screening or supplementation.


Assuntos
Doenças Cardiovasculares/patologia , Espessura Intima-Media Carotídea , Infecções por HIV/complicações , Vitamina D/administração & dosagem , Adulto , Canadá , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
5.
Int J Obes (Lond) ; 40(10): 1541-1549, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27339604

RESUMO

BACKGROUND: The Mediterranean diet has been consistently associated with reduced mortality risk. Few prospective studies have examined whether the benefits from a Mediterranean diet are equally shared by obese individuals with varying metabolic health. OBJECTIVE: The objective of this study was to investigate the association between Mediterranean diet, metabolic phenotypes and mortality risk in a representative obese US population. METHODS: Data from 1739 adults aged 20-88 years were analyzed from participants of the National Health and Nutrition Examination Survey III, 1988-1994 followed up for deaths until 31 December 2011 in a prospective cohort analysis. Mediterranean Diet Scores (MDS) were created to assess the adherence to Mediterranean diet. Participants were classified as metabolically healthy obese (MHO) phenotype (0 or 1 metabolic abnormality) or metabolically unhealthy obese (MUO) phenotype (two or more metabolic abnormalities), based on high glucose, insulin resistance, blood pressure, triglycerides, C-reactive protein and low high-density lipoprotein cholesterol. RESULTS: The MHO phenotype (n=598) was observed in 34.8% (s.e., 1.7%) of those who were obese (mean body mass index was 33.4 and 34.8 in MHO and MUO phenotypes, respectively). During a median follow-up of 18.5 years, there were 77 (12.9%) and 309 (27.1%) deaths in MHO and MUO individuals, respectively. In MHO individuals, the multivariable-adjusted hazard ratio (HR) of all-cause mortality in the highest tertile compared with the first tertile of MDS was 0.44 (95% confidence interval (CI), 0.26-0.75; P for trend <0.001), after adjustment for potential confounders. A five-point (1 s.d.) increment in the adherence to MDS was associated with a 41% reduction in the risk of all-cause mortality (HR, 0.59; 95% CI, 0.37-0.94). Similar findings were obtained when we restricted our analyses to those with or without prevalent diabetes mellitus and hypertension. We did not observe mortality risk reduction in either individuals with MUO phenotype or all obese participants combined. CONCLUSIONS: Adherence to a Mediterranean dietary pattern appears to reduce mortality in the MHO phenotype, but not among the MUO phenotype in an obese population.


Assuntos
Doenças Cardiovasculares/mortalidade , Dieta Mediterrânea , Síndrome Metabólica/mortalidade , Obesidade Metabolicamente Benigna/mortalidade , Obesidade/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/prevenção & controle , Feminino , Humanos , Masculino , Síndrome Metabólica/prevenção & controle , Pessoa de Meia-Idade , Inquéritos Nutricionais , Obesidade/prevenção & controle , Obesidade Metabolicamente Benigna/prevenção & controle , Cooperação do Paciente/estatística & dados numéricos , Fenótipo , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores Socioeconômicos , Estados Unidos/epidemiologia , Adulto Jovem
6.
Oral Dis ; 22(7): 709-14, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27388365

RESUMO

OBJECTIVE: To evaluate the association between oral health and ventilator-associated pneumonia (VAP) among critically ill patients. METHODS: A prospective cohort study was conducted among 162 critically ill patients newly intubated and treated with mechanical ventilator in one tertiary hospital in Thailand. Oral health status was assessed using Oral Health Assessment Tool (OHAT), Plaque Index (PI), and number of teeth. VAP, defined as Clinical Pulmonary Infection Score >6, was assessed on Day 4 after intubation. Hazard ratios and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression adjusted for confounders. RESULTS: Critically ill patients had deteriorating oral health status after intubation. Early-onset VAP developed in 69 patients (42.6%), with VAP incidence of 117 episodes per 1000 ventilator-days. Moderately unhealthy and unhealthy oral conditions based on OHAT scores were associated with a 2.92-fold (95% CI: 1.26-6.74) and 3.22-fold (95% CI: 1.34-7.76) increased risk of VAP. Patients with moderate-to-very poor oral hygiene assessed by PI had increased VAP risk of 1.66-folds (95% CI: 1.001-2.75). The number of teeth was not associated with VAP development. CONCLUSIONS: There is a strong association between poor oral health and increased risk for early-onset VAP. Routine oral care possibly prevents VAP development among critically ill patients treated with mechanical ventilator.


Assuntos
Estado Terminal , Saúde Bucal , Pneumonia Associada à Ventilação Mecânica/etiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Prospectivos
7.
Sci Rep ; 13(1): 16603, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37789139

RESUMO

Eragrostis curvula is an agronomically and ecologically undesirable perennial tussock grass dispersed across Australia. The objective of this study is to investigate relationships of ecologically relevant abiotic variables with the presence of E. curvula at a landscape scale in the Snowy Monaro region, Australia. Through vegetation surveys across 21 privately owned properties and freely available ancillary data on E. curvula presence, we used seven predictor variables, including Sentinel 2 NDVI reflectance, topography, distance from roads and watercourses and climate, to predict the presence or absence of E. curvula across its invaded range using a random forest (RF) algorithm. Assessment of performance metrics resulted in a pseudo-R squared of 0.96, a kappa of 0.97 and an R squared for out-of-bag samples of 0.67. Temperature had the largest influence on the model's performance, followed by linear features such as highways and rivers. Highways' high importance in the model may indicate that the presence or absence of E. curvula is related to the density of human transit, thus as a vector of E. curvula propagule dispersal. Further, humans' tendency to reside adjacent to rivers may indicate that E. curvula's presence or absence is related to human density and E. curvula's potential to spread via water courses.


Assuntos
Eragrostis , Humanos , Pradaria , Algoritmo Florestas Aleatórias , Austrália , Poaceae
8.
JDR Clin Trans Res ; 8(2): 148-157, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35139675

RESUMO

INTRODUCTION: Markers of poor oral health are associated with impaired cognition and higher risk of Alzheimer disease (AD) and thus may help predict AD. OBJECTIVES: The aim of this study was to evaluate the cross-sectional association between empirically derived groups of 19 IgG antibodies against periodontal microorganisms and cognition in middle-aged and older adults. METHODS: The study population consisted of participants of the third National Health and Nutrition Examination Survey (NHANES III) (1988 to 1994), who were 60 y and older, among whom cognition and IgG antibodies against 19 periodontal microorganisms were measured (N = 5,162). RESULTS: In multivariable quantile regression analyses, the Orange-Red (Prevotella melaninogenica, Prevotella intermedia, Prevotella nigrescens, Porphyromonas gingivalis) and Yellow-Orange (Staphylococcus intermedius, Streptococcus oralis, Streptococcus mutans, Fusobacterium nucleatum, Peptostreptococcus micros, Capnocytophaga ochracea) cluster scores were negatively associated with cognition. A 1-unit higher cluster score for the Orange-Red cluster was associated on average with a lower cognitive score (ß for 30th quantile = -0.2640; 95% confidence interval [CI], -0.3431 to -0.1848). Similarly, a 1-unit higher score for the Yellow-Orange cluster was associated with a lower cognitive score (ß for 30th quantile = -0.2445; 95% CI, -0.3517 to -0.1372). CONCLUSION: Groups of IgG antibodies against periodontal microorganisms were associated with lower cognition among free living adults 60 years and older, who were previously undiagnosed with cognitive impairment. Though poor oral health precedes the development of dementia and AD, oral health information is currently not used, to our knowledge, to predict dementia or AD risk. Combining our findings with current algorithms may improve risk prediction for dementia and AD. KNOWLEDGE TRANSLATION STATEMENT: IgG antibodies against periodontal microorganisms were associated with lower cognition among adults 60 years and older previously undiagnosed with cognitive impairment. Periodontal disease may predict cognition among older adults.


Assuntos
Cognição , Imunoglobulina G , Periodonto , Estudos Transversais , Demência , Periodontite , Periodonto/microbiologia , Saúde Bucal , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais
9.
J Hum Nutr Diet ; 24(2): 128-34, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21332835

RESUMO

BACKGROUND: The higher consumption of fruit and vegetables is considered to be an indicator of healthy eating and the protective effects of fruit and vegetable (FV) consumption for noncommunicable diseases have been investigated extensively. The present study aimed to investigate the association between fruit and vegetable intake (FVI), health behaviours and socio-demographic factors among adult Canadians. METHODS: This analysis was based on the information from the Canadian Community Health Survey, Cycle 3.1. Daily intake of fruit and vegetables from a total number of 15,512 apparently healthy individuals, aged 18-64 years, were assessed using a structured questionnaire, which included 20 questions on the frequency of consumption of different types of fruit and vegetables. Multiple logistic regression models were used to determine the association between FVI and some socio-economic factors and lifestyle behaviour among adult Canadians. RESULTS: In total 77% of Canadian adults consumed fruit and vegetables less than five times per day. Females were more likely to consume more fruit [odds ratio (OR) 2.05; 95% confidence interval (CI) 1.75-2.4], vegetables (OR 1.95; 95% CI 1.65-2.29) and FV (OR 2.52; 95% CI 2.20-2.90) than males. Single/never married individuals, individuals with higher levels of education, never smokers, former drinkers and older people reported more consumption of fruit and vegetables than others. CONCLUSIONS: The results obtained in the present study indicate an association between FVI and some socio-economic and healthy lifestyle behaviours, and that a substantial gap exists between the recommended level and the actual intake of the FV among the Canadian population. Because a higher intake of FV improves public health, it is imperative to tailor nutrition education at the individual and community levels in Canadian populations.


Assuntos
Dieta/estatística & dados numéricos , Comportamento Alimentar , Comportamentos Relacionados com a Saúde , Fatores Socioeconômicos , Adolescente , Adulto , Fatores Etários , Consumo de Bebidas Alcoólicas , Canadá , Intervalos de Confiança , Feminino , Frutas , Inquéritos Epidemiológicos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores Sexuais , Fumar , Inquéritos e Questionários , Verduras , Adulto Jovem
10.
Hernia ; 25(2): 287-293, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32361947

RESUMO

PURPOSE: Lower socioeconomic status has been shown to be predictive of poorer surgical outcomes in ventral hernia repair. Recently, safety-net hospitals have been attempting to address these disparities to improve the care of patients of lower socioeconomic status. METHODS: A query of all patients undergoing ventral hernia repair at our institution between 2010 and 2019 was completed (n = 580). Patients not from identifiable New Jersey ZIP-codes were excluded (n = 572). ZIP codes were assigned quartiles based off socioeconomic variables including median household income, percent below poverty line, and high school graduation rate. Patients were then assigned to socioeconomic status quartiles based off their residential ZIP-code. Outcomes of ventral hernia surgery were compared across ZIP-code quartiles. Logistic regression was used to analyze predictors of poor outcomes. RESULTS: Patients from lower socioeconomic brackets were more likely to be younger (p < 0.001), female (p = 0.014), black (p < 0.001), and/or Hispanic (p = 0.003). Most notably, outcomes of ventral hernia were not significantly different between patients of different socioeconomic status ZIP-code quartiles. The risk of any post-operative morbidity was higher for longer procedures (p < 0.001) and for hernia repairs being done with other procedures (p < 0.001). Risk of prolonged length of stay and related 30-day readmission was higher with longer procedures (p < 0.001 and p = 0.003, respectively). CONCLUSION: We found that outcomes of ventral hernia repair at a safety-net hospital were unaffected by socioeconomic status. This supports the important role that safety-net institutions play in providing quality care to their vulnerable populations. Future studies at other safety-net hospitals should be done to further assess the updated impact of socioeconomic status on ventral hernia outcomes.


Assuntos
Hérnia Ventral , Provedores de Redes de Segurança , Feminino , Hérnia Ventral/cirurgia , Herniorrafia/efeitos adversos , Humanos , Fatores de Risco , Determinantes Sociais da Saúde
11.
Int J Popul Data Sci ; 4(2): 1138, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32935040

RESUMO

Established in 1995, the Western Australian Data Linkage Branch (DLB) is Australia's longest running data linkage agency. The Western Australian Data Linkage System (WADLS) employs an enduring linkage model spanning over 60 data collections supported by internally developed and supported software and IT infrastructure. DLB has delivered, and continues to deliver, a range of significant data linkage innovations, many of which have been adopted elsewhere. A current restructure within the Western Australian Department of Health (which we will refer to as the Department of Health) will provide an improved funding model geared toward addressing issues with staff retention, capacity and customer service, as well as fostering improvements to data management, governance and availability. Research using linked data provided by DLB has been used in over 800 projects resulting in over 2350 publications and outcomes for policy development, service delivery and public health. Demand continues to grow for data linkage services and with the Department of Health's bolstered commitment to resourcing, DLB looks forward to a future for data linkage in Western Australia that is sustainable, high quality, efficient, and safe.

12.
JDR Clin Trans Res ; 5(2): 166-175, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31277564

RESUMO

INTRODUCTION: Periodontitis is a chronic inflammatory condition initiated by microorganisms and is positively linked to systemic conditions such as cancer, cardiovascular disease, and diabetes mellitus. OBJECTIVES: To prospectively investigate associations between empirically derived clusters of IgG antibodies against 19 selected periodontal microorganisms and cancer mortality in a representative sample of the US population. METHODS: We evaluated 6,491 participants aged ≥40 y from the Third National Health and Nutrition Examination Survey (1988 to 1994), who had complete data on IgG antibody titers against 19 selected periodontal microorganisms and were free of cardiovascular disease and cancer. In a prior study, antibodies were categorized into 4 mutually exclusive groups via cluster analysis: red-green, orange-red, yellow-orange, and orange-blue. Cluster scores were estimated by summing z scores of the antibody titers making up each cluster. Participants were followed up to death until December 31, 2011. Cox proportional hazard models were applied to estimate hazard ratios (HRs) and 95% CIs for all-cancer mortality by tertiles of cluster scores. RESULTS: During follow-up for a median of 15.9 y, there were 2,702 deaths (31.3%), including 631 cancer-related deaths (8.1%). After adjusting for multiple confounders, the orange-blue cluster was inversely associated with cancer mortality (tertile 2 vs. tertile 1: HR = 0.67, 95% CI = 0.54 to 0.84; tertile 3 vs tertile 1: HR = 0.62, 95% CI = 0.46 to 0.84). The association between the yellow-orange cluster and all-cancer mortality was also inverse but not significant, and the orange-red cluster and the red-green cluster were not associated with all-cancer mortality. CONCLUSIONS: Antibodies against Eubacterium nodatum and Actinomyces naeslundii may be novel predictors of cancer mortality. If further studies establish a causal relationship between these antibodies and cancer mortality, they could be targets to prevent possible systemic effects of periodontal disease with potential interventions to raise their levels. KNOWLEDGE TRANSFER STATEMENT: Periodontal antibodies against Eubacterium nodatum and Actinomyces naeslundii were inversely associated with cancer mortality among adults followed up for an average of 16 y. Periodontal antibodies may predict cancer mortality.


Assuntos
Neoplasias , Periodontite , Actinomyces , Anticorpos Antibacterianos , Humanos , Imunoglobulina G
13.
J Dent Res ; 99(1): 51-59, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31634041

RESUMO

Periodontitis is positively linked to cardiovascular disease (CVD), diabetes, cancer, and increased mortality. Empirically derived clusters of IgG antibodies against 19 selected periodontal microorganisms have been associated with hyperglycemia. We further investigated associations between these serum IgG antibody clusters and all-cause and CVD mortality in a representative US population. Participants free of CVD and cancer and aged ≥40 y at baseline (N = 6,491) from the Third National Health and Nutrition Examination Survey (1988 to 1994) were followed up until December 31, 2011. Antibodies were categorized into 4 clusters: red-green, orange-red, yellow-orange, and orange-blue. Over a 23-y follow-up, 2,702 deaths occurred, including 810 CVD-related deaths. In fully adjusted Cox proportional hazard models, the red-green cluster was positively associated with all-cause mortality (tertile 3 vs. tertile 1: hazard ratio [HR] = 1.43, 95% CI = 1.08 to 1.90, P = 0.015). The yellow-orange cluster was inversely associated with all-cause mortality (tertile 3 vs. tertile 1: HR = 0.78, 95% CI = 0.63 to 0.97, P = 0.028) and CVD mortality (tertile 2 vs. tertile 1: HR = 0.57, 95% CI = 0.42 to 0.77, P = 0.005). The orange-blue cluster (composed of antibodies against Eubacterium nodatum and Actinomyces naeslundii) was inversely associated with all-cause mortality (tertile 3 vs. tertile 1: HR = 0.65, 95% CI = 0.55 to 0.78, P < 0.0001) and CVD mortality (tertile 3 vs. tertile 1: HR = 0.65, 95% CI = 0.47 to 0.88, P = 0.007). These antibodies could predict prognosis or be potential intervention targets to prevent systemic effects of periodontal disease if further studies establish a causal relationship.


Assuntos
Anticorpos Antibacterianos , Doenças Cardiovasculares , Diabetes Mellitus , Hiperglicemia , Periodontite , Actinomyces , Adulto , Idoso , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/mortalidade , Feminino , Humanos , Hiperglicemia/complicações , Hiperglicemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Periodontite/complicações , Periodontite/epidemiologia , Fatores de Risco
14.
Tree Physiol ; 39(2): 332-339, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30551158

RESUMO

Rapid, reliable tools are needed to infer physiological and nutritional health for managing forest systems. Understanding the processes governing tree health is central to the development of these tools. Non-foliar approaches such as the collection of phloem sap reflect processes governing both the use and acquisition of plant water and nutrients at a wide range of temporal (diurnal to seasonal) and spatial (canopy) scales. Despite this, phloem sap is not commonly employed due to an incomplete understanding of transport and post-photosynthetic processes and their effects on chemical concentrations and carbon isotope discrimination. We highlight the need to characterize the influences of storage, remobilization and transport on the concentrations of metabolites to address the time and spatial decoupling of phloem contents to that of environmental stimuli. A conceptual framework is suggested to focus research on key phenomena regarding metabolite transport and highlight significant advantages, misconceptions and limitations to its application.


Assuntos
Floema/metabolismo , Árvores/metabolismo , Nutrientes , Água/metabolismo
15.
Oncoimmunology ; 8(11): e1644109, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31646092

RESUMO

The advancement of immune-therapeutics in cancer treatment has proven to be promising in various malignant diseases. However, in castration resistant prostate cancer (mCRPC) major Phase III trials have been unexpectedly disappointing. To contribute to a broader understanding of the role and use of immune-therapeutics in mCRPC, we conducted a systematic review. We searched the websites ClinicalTrials.gov, PubMed and ASCO Meeting Library for clinical trials employing immune checkpoint inhibitors in mCRPC. This article not only describes the rationale of individual trials, but it also summarizes the current status of the field and sheds light on strategies for future success.

16.
Mol Cell Biol ; 17(6): 3261-71, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9154825

RESUMO

We describe a new minichromosome maintenance factor, Mcm10, and show that this essential protein is involved in the initiation of DNA replication in Saccharomyces cerevisiae. The mcm10 mutant has an autonomously replicating sequence-specific minichromosome maintenance defect and arrests at the nonpermissive temperature with dumbbell morphology and 2C DNA content. Mcm10 is a nuclear protein that physically interacts with several members of the MCM2-7 family of DNA replication initiation factors. Cloning and sequencing of the MCM10 gene show that it is identical to DNA43, a gene identified independently for its putative role in replicating DNA. Two-dimensional DNA gel analysis reveals that the mcm10-1 lesion causes a dramatic reduction in DNA replication initiation at chromosomal origins, including ORI1 and ORI121. Interestingly, the mcm10-1 lesion also causes replication forks to pause during elongation through these same loci. This novel phenotype suggests a unique role for the Mcm10 protein in the initiation of DNA synthesis at replication origins.


Assuntos
Proteínas de Ciclo Celular , Ciclo Celular/genética , Replicação do DNA , DNA Fúngico/biossíntese , Proteínas Fúngicas/metabolismo , Proteínas Nucleares/metabolismo , Origem de Replicação/efeitos dos fármacos , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Alelos , Divisão Celular , Núcleo Celular/química , Proteínas Cromossômicas não Histona , Clonagem Molecular , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Proteínas de Manutenção de Minicromossomo , Proteínas Nucleares/química , Proteínas Nucleares/genética , Conformação de Ácido Nucleico , Fenótipo , Plasmídeos/metabolismo , Temperatura
17.
Nat Biotechnol ; 16(7): 677-81, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9661204

RESUMO

Production of bispecific IgG (BsIgG) by coexpressing two different antibodies is inefficient due to unwanted pairings of the component heavy and light chains. To overcome this problem, heavy chains were remodeled for heterodimerization using engineered disulfide bonds in combination with previously identified "knobs-into-holes" mutations. One of the variants, S354C:T366W/Y349'C:T366'S:L368'A:Y407++ +'V, gave near quantitative (approximately 95%) heterodimerization. Light chain mispairing was circumvented by using an identical light chain for each arm of the BsIgG. Antibodies with identical light chains that bind to different antigens were identified from an scFv phage library with a very restricted light chain repertoire for the majority (50/55) of antigen pairs tested. A BsIgG capable of simultaneously binding to the human receptors HER3 and cMpI was prepared by coexpressing the common light chain and corresponding remodeled heavy chains followed by protein A chromatography. The engineered heavy chains retain their ability to support antibody-dependent cell-mediated cytotoxicity as demonstrated with an anti-HER2 antibody.


Assuntos
Especificidade de Anticorpos/imunologia , Imunoglobulina G/biossíntese , Proteínas de Neoplasias , Receptores Imunológicos/metabolismo , Complexo Antígeno-Anticorpo , Citotoxicidade Imunológica , Dimerização , Dissulfetos , Receptores ErbB/metabolismo , Humanos , Imunoglobulina G/genética , Imunoglobulina G/imunologia , Modelos Moleculares , Mutação/genética , Engenharia de Proteínas , Proteínas Proto-Oncogênicas/metabolismo , Receptor ErbB-3 , Receptores de Citocinas/metabolismo , Receptores de Trombopoetina
19.
Hernia ; 21(6): 855-867, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28864961

RESUMO

PURPOSE: Although studies have implicated smoking as a positive predictor of post-operative outcomes in inguinal hernia repair, its impact on ventral hernia repair (VHR) is not as clear. This study aims to fill this gap by investigating the impact of smoking on developing adverse 30-day post-operative outcomes in VHR. METHODS: Patients undergoing VHR between 2005 and 2014 were extracted from the American College of Surgeons National Surgical Quality Improvement Program database. Patients were stratified by smoking status and compared for significant differences in baseline characteristics. Logistic regression modeled the impact of smoking on the primary outcome variable of 30-day mortality and the secondary outcome variables of 30-day overall, cardiac, respiratory, or wound morbidity. To evaluate the influence of smoking in comparable groups undergoing VHR, a propensity score matched analysis was performed. RESULTS: Out of 169,458 patients identified, 32,973 (19.5%) were classified as current smokers. Smokers and non/ex-smokers differed significantly in multiple pre-operative baseline characteristics. Unmatched univariate analyses revealed smoking status as a positive predictor of every post-operative outcome. These findings were validated with propensity score matching analyses, which found current smokers have an increased likelihood of 30-day mortality (OR 1.42), overall morbidity (OR 1.39), wound (OR 1.40), respiratory (OR 1.14), or cardiac morbidity (OR 1.88) compared to non/ex-smokers (p < 0.05 for all). CONCLUSIONS: Smoking is a modifiable risk factor with a detrimental impact on outcomes in patients undergoing ventral hernia repair. Delaying VHR and promoting smoking cessation prior to surgery may help reduce the odds of adverse 30-day post-operative outcomes.


Assuntos
Hérnia Ventral/cirurgia , Herniorrafia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Fumar/efeitos adversos , Adulto , Idoso , Bases de Dados Factuais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Melhoria de Qualidade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Estados Unidos
20.
JDR Clin Trans Res ; 2(2): 168-178, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30931777

RESUMO

The objective of this study was to evaluate the relation between alcohol intake and groups of periodontal antibody titers among individuals with normal glucose tolerance (NGT), prediabetes and diabetes. This was a cross-sectional analysis of the National Health and Nutrition Examination Survey III (NHANES III) 1988-1994 data, among individuals 40 y and older with information on alcohol intake and serum immunoglobulin G (IgG) antibody data against 19 oral microorganisms. Participants were excluded if they did not have teeth, reported that they were taking insulin, or having gestational diabetes. The sample size for this analysis was 3,219. Periodontal antibodies were grouped into four clusters using cluster analysis: Orange-Red, Red-Green, Yellow- Orange, and Orange-Blue. Cluster scores were computed for each individual by summing z-scores of standardized log-transformed IgG titers of antibodies against periodontal microorganisms making up each respective cluster. Each cluster score was modeled as an outcome. Alcohol consumption was assessed in g/day using self-reported number of days of drinking in the past 12 mo and the average number of drinks consumed per day on days when they drank. Overall, alcohol intake was positively associated with periodontal antibodies of the Orange-Red cluster (P. melaninogenica, P. intermedia, P. nigrescens, and P. gingivalis), and inversely associated with the Yellow-Orange cluster (S. intermedius, S. oralis, S. mutans, F. nucleatum, P. micra, C. ochracea) after multivariable adjustment. The association between alcohol intake and the Orange-Red cluster was strongest among individuals with diabetes; this relation was seen among individuals with and without periodontal damage. The Orange-Red cluster was positively associated with periodontal damage among individuals with diabetes. Alcohol intake was not associated with any antibody cluster among individuals with NGT or prediabetes. The effect of alcohol intake on periodontal disease may be greater among individuals with diabetes but this finding needs to be confirmed in prospective studies. Knowledge Transfer Statement: The results of this study can be used by clinicians when treating patients with periodontal disease and diabetes.

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