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People share information for many reasons. For example, Berger (2011, N = 40) found that undergraduate participants manipulated to have higher physiological arousal were more likely to share a news article with others via email than people who had low arousal. Berger's research is widely cited as evidence of the causal role of arousal in sharing information and has been used to explain why information that induces high-arousal emotions is shared more than information that induces low-arousal emotions. We conducted two replications (N = 111, N = 160) of Berger's study, using the same arousal manipulation but updating the sharing measure to reflect the rise of information sharing through social media. Both studies failed to find an impact of incidental physiological arousal on undergraduate participants' willingness to share news articles on social media. Our studies cast doubt on the idea that incidental physiological arousal-in the absence of other factors-impacts people's decisions to share information on social networking sites.
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Both type 1 and type 2 diabetes mellitus are advancing at exponential rates, placing significant burdens on health care networks worldwide. Although traditional pharmacologic therapies such as insulin and oral antidiabetic stalwarts like metformin and the sulfonylureas continue to be used, newer drugs are now on the market targeting novel blood glucose-lowering pathways. Furthermore, exciting new developments in the understanding of beta cell and islet biology are driving the potential for treatments targeting incretin action, islet transplantation with new methods for immunologic protection, and the generation of functional beta cells from stem cells. Here we discuss the mechanistic details underlying past, present, and future diabetes therapies and evaluate their potential to treat and possibly reverse type 1 and 2 diabetes in humans. SIGNIFICANCE STATEMENT: Diabetes mellitus has reached epidemic proportions in the developed and developing world alike. As the last several years have seen many new developments in the field, a new and up to date review of these advances and their careful evaluation will help both clinical and research diabetologists to better understand where the field is currently heading.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemiantes/uso terapêutico , InsulinaRESUMO
In this technical note, we primarily demonstrate the computation of confidence limits for a novel measure of average lifespan shortened (ALSS). We identified women who had died from cervical and ovarian cancer between 2000 and 2020 from the Alberta cancer registry. Years of life lost (YLL) was calculated using the national life tables of Canada. We estimated the ALSS as a ratio of YLL in relation to the expected lifespan. We computed the confidence limits of the measure using various approaches, including the normal distribution, gamma distribution, and bootstrap method. The new ALSS measure shows a modest gain in lifespan of women, particularly women with ovarian cancer, over the study period.
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Longevidade , Neoplasias Ovarianas , Humanos , Feminino , Expectativa de Vida , Alberta , Tábuas de VidaRESUMO
ABSTRACT: Walker, EJ, Aughey, RJ, McLaughlin, P, and McAinch, AJ. Seasonal change in body composition and physique of team sport athletes. J Strength Cond Res 36(2): 565-572, 2022-Body composition of team sport athletes was measured at 3 points across the preseason and competitive season. This repeated-measures study was conducted in 46 professional Australian football (AF) (age 23.8 ± 3.8 years), 26 soccer (age 22.7 ± 4.7 years), and 33 rugby union players (age 28.1 ± 4.2 years). A mixed-design analysis of variance was used to determine change across the season, and Pearson's correlation was used to determine the relationship between different measures. Anthropometry, dual-energy x-ray absorptiometry (DXA), and 3-dimensional (3D) scan technology were used in AF and soccer, whereas only DXA was used in rugby. Body mass remained unchanged for both AF and soccer with gains in lean mass (p < 0.01), from preseason to early in the competitive season. Skinfold measures declined in AF (p < 0.001) and soccer (p < 0.05) across the season, whereas DXA-measured fat mass only declined in soccer (p < 0.01). Rugby backs (p < 0.01) and forwards (p < 0.001) reduced body fat and gained lean mass from preseason to in-season with forwards having greater relative and absolute changes as measured by DXA. 3D technology did not show change across the season. Dual-energy x-ray absorptiometry body fat percent and the sum of skinfold correlation were large (r = 0.74 [p < 0.001, CI 0.67-0.81]). The greatest change in body composition occurs from the beginning of preseason to the start of competition, with changes returning to baseline levels toward the end of season. Dual-energy x-ray absorptiometry and skinfold measures were moderately correlated, providing a good alternative to track change in subcutaneous fat in AF and soccer athletes.
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Rugby , Esportes de Equipe , Absorciometria de Fóton , Adolescente , Adulto , Atletas , Austrália , Composição Corporal , Humanos , Estações do Ano , Adulto JovemRESUMO
AbstractIn symbiotic interactions, spatiotemporal variation in the distribution or population dynamics of one species represents spatial and temporal heterogeneity of the landscape for the other. Such interdependent demographic dynamics result in situations where the relative importance of biotic and abiotic factors in determining ecological processes is complicated to decipher. Using a detailed survey of three metapopulations of the succulent plant Cakile maritima and the necrotrophic fungus Alternaria brassicicola located along the southeastern Australian coast, we developed a series of statistical analyses-namely, synchrony analysis, patch occupancy dynamics, and a spatially explicit metapopulation model-to understand how habitat quality, weather conditions, dispersal, and spatial structure determine metapopulation dynamics. Climatic conditions are important drivers, likely explaining the high synchrony among populations. Host availability, landscape features facilitating dispersal, and habitat conditions also impact the occurrence and spread of disease. Overall, we show that the collection of extensive data on host and pathogen population dynamics, in combination with spatially explicit epidemiological modeling, makes it possible to accurately predict disease dynamics-even when there is extreme variability in host population dynamics. Finally, we discuss the importance of genetic information for predicting demographic dynamics in this pathosystem.
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Alternaria/fisiologia , Brassicaceae/microbiologia , Interações Hospedeiro-Patógeno , Doenças das Plantas/microbiologia , Clima , Ecossistema , New South Wales , Dinâmica Populacional , Dispersão de SementesRESUMO
The ß-cell-enriched MAFA transcription factor plays a central role in regulating glucose-stimulated insulin secretion while also demonstrating oncogenic transformation potential in vitro. No disease-causing MAFA variants have been previously described. We investigated a large pedigree with autosomal dominant inheritance of diabetes mellitus or insulinomatosis, an adult-onset condition of recurrent hyperinsulinemic hypoglycemia caused by multiple insulin-secreting neuroendocrine tumors of the pancreas. Using exome sequencing, we identified a missense MAFA mutation (p.Ser64Phe, c.191C>T) segregating with both phenotypes of insulinomatosis and diabetes. This mutation was also found in a second unrelated family with the same clinical phenotype, while no germline or somatic MAFA mutations were identified in nine patients with sporadic insulinomatosis. In the two families, insulinomatosis presented more frequently in females (eight females/two males) and diabetes more often in males (12 males/four females). Four patients from the index family, including two homozygotes, had a history of congenital cataract and/or glaucoma. The p.Ser64Phe mutation was found to impair phosphorylation within the transactivation domain of MAFA and profoundly increased MAFA protein stability under both high and low glucose concentrations in ß-cell lines. In addition, the transactivation potential of p.Ser64Phe MAFA in ß-cell lines was enhanced compared with wild-type MAFA. In summary, the p.Ser64Phe missense MAFA mutation leads to familial insulinomatosis or diabetes by impacting MAFA protein stability and transactivation ability. The human phenotypes associated with the p.Ser64Phe MAFA missense mutation reflect both the oncogenic capacity of MAFA and its key role in islet ß-cell activity.
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Diabetes Mellitus/genética , Hiperinsulinismo/genética , Insulinoma/genética , Fatores de Transcrição Maf Maior/genética , Proteínas Mutantes/genética , Mutação de Sentido Incorreto , Tumores Neuroendócrinos/genética , Neoplasias Pancreáticas/genética , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Feminino , Genes Dominantes , Humanos , Hiperinsulinismo/metabolismo , Hiperinsulinismo/patologia , Insulinoma/metabolismo , Insulinoma/patologia , Fatores de Transcrição Maf Maior/metabolismo , Masculino , Proteínas Mutantes/metabolismo , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Linhagem , Estabilidade Proteica , Ativação Transcricional , Sequenciamento do ExomaRESUMO
Field cultivation of Genetically Modified (GM) Bt-plants has a potential environmental risk toward non-target Lepidoptera (NTLs) larvae through the consumption of Bt-maize pollen. The Bt-maize Cry protein targeting Lepidoptera species detrimental to the crop is also expressed in pollen which is dispersed by wind and can thus reach habitats of NTLs. To better assess the current ecological risk of Bt-maize at landscape scales, we developed a spatially-explicit exposure-hazard model considering (i) the dynamics of pollen dispersal obtained by convolving GM plants emission with a dispersal kernel and (ii) a toxicokinetic-toxicodynamic (TKTD) model accounting for the impact of toxin ingestion on individual lethal effects. We simulated the model using real landscape observations in Catalonia (Spain): GM-maize locations, flowering dates, rainfall time series and larvae emergence date of the European peacock butterfly Aglais io. While in average, the additional mortality appears to be negligible, we show significant additional mortality at sub-population level, with for instance a mortality higher than 40% within the 10m for the 10% most Bt-sensitive individuals. Also, using Pareto optimality we capture the best trade-off between isolation distance and additional mortality: up to 50 m are required to significantly buffer Bt-pollen impact on NTLs survival at the individual level. Our study clears up the narrow line between diverging conclusions: those claiming no risk by only looking at the average regional effect of Bt on NTLs survival and those pointing out a significant threaten when considering the variability of individuals mortality.
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Toxinas de Bacillus thuringiensis/toxicidade , Borboletas/fisiologia , Endotoxinas/toxicidade , Proteínas Hemolisinas/toxicidade , Plantas Geneticamente Modificadas/fisiologia , Zea mays/fisiologia , Animais , Bacillus thuringiensis/genética , Proteínas de Bactérias/metabolismo , Borboletas/efeitos dos fármacos , Borboletas/metabolismo , Endotoxinas/metabolismo , Proteínas Hemolisinas/genética , Larva/efeitos dos fármacos , Plantas Geneticamente Modificadas/metabolismo , Pólen , Espanha , Zea mays/genéticaRESUMO
This experimental study reveals intriguing thermoelectric effects and devices in epitaxial bismuthene, two-dimensional (2D) bismuth with thickness ⩽30 nm, on Si (111). Bismuthene exhibits interesting anisotropic Seebeck coefficients varying 2-5 times along different crystal orientations, implying the existence of a puckered atomic structure like black phosphorus. An absolute value of Seebeck coefficient up to 237 µV K-1 sets a record for elemental Bi ever measured to the best of our knowledge. Electrical conductivity of bismuthene can reach up to 4.6 × 104 S m-1, which is sensitive to thickness and magnetic field. Along with a desired low thermal conductivity â¼1.97 W m-1 K that is 20% of its bulk form, the first experimental zT value at room temperature for bismuthene was measured â¼10-2, which is much higher than many other VA Xenes and comparable to its bulk compounds. Above results suggest a mixed buckled and puckered Bi atomic structure for epitaxial 2D bismuth on Si (111). Our work paves the way to explore potential applications, such as heat flux sensor, energy converting devices and so on for bismuthene.
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BACKGROUND: Methylmercury contamination of the environment represents a substantial environmental health concern. Human exposure to methylmercury occurs primarily through consumption of fish and marine mammals. Heavily exposed subgroups include sport or subsistence fishers residing in Arctic communities. We aimed to estimate the association of fish/whale consumption patterns of Canadian Arctic subsistence fishers with the internal dose of methylmercury as measured in hair. METHODS: This research was conducted within ongoing community projects led by the CANHelp Working Group in Aklavik and Fort McPherson, Northwest Territories and Old Crow, Yukon. We interviewed each participant using a fish-focused food-frequency questionnaire during September-November 2016 and collected hair samples concurrently. Methylmercury was measured in the full-length of each hair sample using gas chromatography inductively-coupled plasma-mass spectrometry. Multivariable linear regression estimated beta-coefficients and 95% confidence intervals (CIs) for the effect of fish/whale consumption on hair-methylmercury concentrations. RESULTS: Among 101 participants who provided hair samples and diet data, the mean number of fish/whale species eaten was 3.5 (SD:1.9). The mean hair-methylmercury concentration was 0.60 µg/g (SD:0.47). Fish/whale consumption was positively associated with hair-methylmercury concentration, after adjusting for sex, hair length and use of permanent hair treatments. Hair-methylmercury concentrations among participants who consumed the most fish/whale in each season ranged from 0.30-0.50 µg/g higher than those who consumed < 1 meal/week. CONCLUSIONS: In this population of Canadian Arctic subsistence fishers, hair-methylmercury concentration increased with fish/whale consumption, but the maximum concentrations were below Health Canada's 6.0 µg/g threshold for safe exposure.
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Dieta/estatística & dados numéricos , Contaminação de Alimentos/análise , Cabelo/química , Compostos de Metilmercúrio/análise , Alimentos Marinhos/análise , Adulto , Animais , Regiões Árticas , Dieta/métodos , Feminino , Peixes , Humanos , Estudos Longitudinais , Masculino , Territórios do Noroeste , Estações do Ano , Baleias , YukonRESUMO
BACKGROUND: Indigenous communities across the circumpolar north have elevated H. pylori (Hp) prevalence and stomach cancer incidence. We aimed to describe the Hp-associated disease burden among western Canadian Arctic participants in community-driven projects that address concerns about health risks from Hp infection. METHODS: During 2008-2013, participants underwent Hp screening by urea breath test and gastroscopy with gastric biopsies. We estimated Hp prevalence and prevalence by Hp status of endoscopic and histopathologic diagnoses. RESULTS: Among 878 participants with Hp status data, Hp prevalence was: 62% overall; 66% in 740 Indigenous participants; 22% in 77 non-Indigenous participants (61 participants did not disclose ethnicity); 45% at 0-14 years old, 69% at 15-34 years old, and 61% at 35-96 years old. Among 309 participants examined endoscopically, visible mucosal lesions were more frequent in the stomach than the duodenum: the gastric to duodenal ratio was 2 for inflammation, 8 for erosions, and 3 for ulcers. Pathological examination in 308 participants with gastric biopsies revealed normal gastric mucosa in 1 of 224 Hp-positive participants and 77% (65/84) of Hp-negative participants with sharp contrasts in the prevalence of abnormalities between Hp-positive and Hp-negative participants, respectively: moderate-severe active gastritis in 50 and 0%; moderate-severe chronic gastritis in 91 and 1%; atrophic gastritis in 43 and 0%; intestinal metaplasia in 17 and 5%. CONCLUSIONS: The observed pattern of disease is consistent with increased risk of stomach cancer and reflects substantial inequity in the Hp-associated disease burden in western Arctic Canadian hamlets relative to most North American settings. This research adds to evidence that demonstrates the need for interventions aimed at reducing health risks from Hp infection in Indigenous Arctic communities.
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Efeitos Psicossociais da Doença , Gastrite/epidemiologia , Infecções por Helicobacter/epidemiologia , Helicobacter pylori , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Regiões Árticas/epidemiologia , Biópsia , Testes Respiratórios , Canadá/epidemiologia , Criança , Pré-Escolar , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite/microbiologia , Gastroscopia/estatística & dados numéricos , Infecções por Helicobacter/microbiologia , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Metaplasia , Pessoa de Meia-Idade , Prevalência , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/microbiologia , Adulto JovemRESUMO
We developed a simulation model for quantifying the spatio-temporal distribution of contaminants (e.g., xenobiotics) and assessing the risk of exposed populations at the landscape level. The model is a spatio-temporal exposure-hazard model based on (i) tools of stochastic geometry (marked polygon and point processes) for structuring the landscape and describing the exposed individuals, (ii) a dispersal kernel describing the dissemination of contaminants from polygon sources, and (iii) an (eco)toxicological equation describing the toxicokinetics and dynamics of contaminants in affected individuals. The model was implemented in the briskaR package (biological risk assessment with R) of the R software. This article presents the model background, the use of the package in an illustrative example, namely, the effect of genetically modified maize pollen on nontarget Lepidoptera, and typical comparisons of landscape configurations that can be carried out with our model (different configurations lead to different mortality rates in the treated example). In real case studies, parameters and parametric functions encountered in the model will have to be precisely specified to obtain realistic measures of risk and impact and accurate comparisons of landscape configurations. Our modeling framework could be applied to study other risks related to agriculture, for instance, pathogen spread in crops or livestock, and could be adapted to cope with other hazards such as toxic emissions from industrial areas having health effects on surrounding populations. Moreover, the R package has the potential to help risk managers in running quantitative risk assessments and testing management strategies.
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Ecologia , Medição de Risco/métodos , Xenobióticos/química , Agricultura , Algoritmos , Animais , Borboletas , Simulação por Computador , Produtos Agrícolas , Engenharia Genética , Humanos , Gado , Modelos Biológicos , Organismos Geneticamente Modificados , Doenças das Plantas , Pólen , Modelos de Riscos Proporcionais , Software , Toxicologia , Zea mays/genéticaRESUMO
Binaural pitch fusion is the fusion of dichotically presented tones that evoke different pitches between the ears. In normal-hearing (NH) listeners, the frequency range over which binaural pitch fusion occurs is usually <0.2 octaves. Recently, broad fusion ranges of 1-4 octaves were demonstrated in bimodal cochlear implant users. In the current study, it was hypothesized that hearing aid (HA) users would also exhibit broad fusion. Fusion ranges were measured in both NH and hearing-impaired (HI) listeners with hearing losses ranging from mild-moderate to severe-profound, and relationships of fusion range with demographic factors and with diplacusis were examined. Fusion ranges of NH and HI listeners averaged 0.17 ± 0.13 octaves and 1.7 ± 1.5 octaves, respectively. In HI listeners, fusion ranges were positively correlated with a principal component measure of the covarying factors of young age, early age of hearing loss onset, and long durations of hearing loss and HA use, but not with hearing threshold, amplification level, or diplacusis. In NH listeners, no correlations were observed with age, hearing threshold, or diplacusis. The association of broad fusion with early onset, long duration of hearing loss suggests a possible role of long-term experience with hearing loss and amplification in the development of broad fusion.
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Auxiliares de Audição , Perda Auditiva/reabilitação , Pessoas com Deficiência Auditiva/psicologia , Pessoas com Deficiência Auditiva/reabilitação , Percepção da Altura Sonora , Estimulação Acústica , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Audiometria de Tons Puros , Limiar Auditivo , Testes com Listas de Dissílabos , Feminino , Perda Auditiva/diagnóstico , Perda Auditiva/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Discriminação da Altura Tonal , Índice de Gravidade de Doença , Adulto JovemRESUMO
We report the first direct dry transfer of a single-crystalline thin film grown by molecular beam epitaxy. A double cantilever beam fracture technique was used to transfer epitaxial bismuth thin films grown on silicon (111) to silicon strips coated with epoxy. The transferred bismuth films retained electrical, optical, and structural properties comparable to the as-grown epitaxial films. Additionally, we isolated the bismuth thin films on freestanding flexible cured-epoxy post-transfer. The adhesion energy at the bismuth/silicon interface was measured to be â¼1 J/m2, comparable to that of exfoliated and wet transferred graphene. This low adhesion energy and ease of transfer is unexpected for an epitaxially grown film and may enable the study of bismuth's unique electronic and spintronic properties on arbitrary substrates. Moreover, this method suggests a route to integrate other group-V epitaxial films (i.e., phosphorus) with arbitrary substrates, as well as potentially to isolate bismuthene, the atomic thin-film limit of bismuth.
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Urinary tract infections (UTIs) are among the most commonly treated bacterial infections. Over the past decade, antimicrobial resistance has become an increasingly common factor in the management of outpatient UTIs. As treatment options for multidrug-resistant (MDR) uropathogens are limited, clinicians need to be aware of specific clinical and epidemiological risk factors for these infections. Based on available literature, the activity of fosfomycin and nitrofurantoin remain high for most cases of MDR Escherichia coli UTIs. Trimethoprim-sulfamethoxazole retains clinical efficacy, but resistance rates are increasing internationally. Beta-lactam agents have the highest rates of resistance and lowest rates of clinical success. Fluoroquinolones have high resistance rates among MDR uropathogens and are being strongly discouraged as first-line agents for UTIs. In addition to accounting for local resistance rates, consideration of patient risk factors for resistance and pharmacological principles will help guide optimal empiric treatment of outpatient UTIs.
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Infecções por Escherichia coli , Infecções Urinárias , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Humanos , Pacientes Ambulatoriais , Fatores de Risco , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/epidemiologia , Infecções Urinárias/microbiologia , Escherichia coli Uropatogênica/efeitos dos fármacosRESUMO
BACKGROUND AND AIMS: BRAF or NRAS mutations occur in approximately 60% of cutaneous melanomas, and the identification of such mutations underpins the appropriate selection of patients who may benefit from BRAF and MEK inhibitor targeted therapies. The utility of immunohistochemistry (IHC) to detect NRAS(Q61L) mutations is currently unknown. This study sought to assess the sensitivity and specificity of anti-BRAF(V600E) (VE1), anti-NRAS(Q61R) (SP174) and anti-NRAS(Q61L) (26193) antibodies for mutation detection in a large series of cases. METHODS AND RESULTS: Mutation status was determined using the OncoCarta assay in 754 cutaneous melanomas. IHC with the anti-BRAF(V600E) antibody was performed in all cases, and the anti-NRAS(Q61R) and anti-NRAS(Q61L) antibodies were assessed in a subset of 302 samples utilizing tissue microarrays. The staining with the anti-BRAF(V600E) and anti-NRAS(Q61R) antibodies was diffuse, homogeneous and cytoplasmic. The anti-NRAS(Q61L) antibody displayed variable intensity staining, ranging from weak to strong in NRAS(Q61L) mutant tumours. The sensitivity and specificity for anti-BRAF(V600E) was 100 and 99.3%, anti-NRAS(Q61R) was 100 and 100% and anti-NRAS(Q61L) was 82.6 and 96.2%, respectively. CONCLUSIONS: The use of IHC is a fast, efficient and cost-effective method to identify single specific mutations in melanoma patients. BRAF(V600E) and NRAS(Q61R) antibodies have high sensitivity and specificity; however, the NRAS(Q61L) antibody appears less sensitive. IHC can help to facilitate the timely, appropriate selection and treatment of metastatic melanoma patients with targeted therapies. Detection of melanoma-associated mutations by IHC may also provide evidence for a diagnosis of melanoma in metastatic undifferentiated neoplasms lacking expression of melanoma antigens.
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Análise Mutacional de DNA/métodos , Análise Mutacional de DNA/normas , GTP Fosfo-Hidrolases/genética , Melanoma/genética , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica/métodos , Imuno-Histoquímica/normas , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Neoplasias Cutâneas , Análise Serial de Tecidos , Melanoma Maligno CutâneoRESUMO
AIMS: Triple-negative breast cancer (TNBC) patients generally have a poor outcome; there is a pressing need to identify more effective therapeutic strategies. Clinical trials targeting programmed death 1/programmed death ligand 1 (PD1/PDL1) in melanoma and non-small-cell lung cancer have reported high response rates, and tumoral PDL1 expression has been suggested as a potential biomarker to enrich for patient response to these treatments. There are only very limited data to date reporting the expression of PDL1 in TNBC. METHODS AND RESULTS: PDL1 immunohistochemistry was performed on 161 primary TNBCs and assessed in the tumour as well as immune cells in the stromal compartment. PDL1 expression was very common in TNBC, expressed in the tumour cell membrane (64%), cytoplasm (80%) and stromal (93%) cellular compartments. Cytoplasmic tumoral expression of PDL1 was associated with a lower risk of breast cancer-specific death [hazard ratio (HR) 0.45, P = 0.035] while stromal PDL1 expression was associated with a lower rate of deaths from all causes (HR 0.305, P = 0.0042). Membranous expression of PDL1 was not associated with outcome. While both PDL1 expression and tumour-infiltrating lymphocytes were associated with a better outcome, only lymphovascular invasion and high tumour-infiltrating lymphocytes were independently prognostic for breast cancer-specific death. CONCLUSION: While PDL1 expression is frequent in TNBC, it was not independently prognostic. There were differences in outcome depending on the cellular compartment of PDL1 expression. These data provide further impetus for investigating the utility of immune checkpoint therapies in TNBC, given the clinical significance of tumour-infiltrating lymphocytes (TILs) and PDL1 expression in this cohort.
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Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Mama/patologia , Linfócitos do Interstício Tumoral/patologia , Melanoma/diagnóstico , Neoplasias de Mama Triplo Negativas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/metabolismo , Estudos de Coortes , Feminino , Humanos , Imuno-Histoquímica , Linfócitos do Interstício Tumoral/metabolismo , Melanoma/metabolismo , Pessoa de Meia-Idade , Prognóstico , Análise Serial de Tecidos , Neoplasias de Mama Triplo Negativas/metabolismoRESUMO
The intestinal epithelium performs vital roles in organ function by absorbing nutrients and providing a protective barrier. The zinc-finger containing transcription factors GATA4 and GATA6 regulate enterocyte gene expression and control regional epithelial cell identity in the adult intestinal epithelium. Although GATA4 and GATA6 are expressed in the developing intestine, loss of either factor alone during the period of epithelial morphogenesis and cytodifferentiation fails to disrupt these processes. Therefore, we tested the hypothesis that GATA4 and GATA6 function redundantly to control these aspects of intestinal development. We used Villin-Cre, which deletes specifically in the intestinal epithelium during the period of villus development and epithelial cytodifferentiation, to generate Gata4Gata6 double conditional knockout embryos. Mice lacking GATA4 and GATA6 in the intestinal epithelium died within 24h of birth. At E18.5, intestinal villus architecture and epithelial cell populations were altered. Enterocytes were lost, and goblet cells were increased. Proliferation was also increased in GATA4-GATA6 deficient intestinal epithelium. Although villus morphology appeared normal at E16.5, the first time at which both Gata4 and Gata6 were efficiently reduced, changes in expression of markers of enterocytes, goblet cells, and proliferative cells were detected. Moreover, goblet cell number was increased at E16.5. Expression of the Notch ligand Dll1 and the Notch target Olfm4 were reduced in mutant tissue indicating decreased Notch signaling. Finally, we found that GATA4 occupies chromatin near the Dll1 transcription start site suggesting direct regulation of Dll1 by GATA4. We demonstrate that GATA4 and GATA6 play an essential role in maintaining proper intestinal epithelial structure and in regulating intestinal epithelial cytodifferentiation. Our data highlight a novel role for GATA factors in fine tuning Notch signaling during intestinal epithelial development to repress goblet cell differentiation.
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Diferenciação Celular/fisiologia , Fator de Transcrição GATA4/metabolismo , Fator de Transcrição GATA6/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Mucosa Intestinal/embriologia , Animais , Proteínas de Ligação ao Cálcio , Diferenciação Celular/genética , Imunoprecipitação da Cromatina , Imunofluorescência , Regulação da Expressão Gênica no Desenvolvimento/genética , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Mucosa Intestinal/citologia , Camundongos , Camundongos Knockout , Análise de Sequência com Séries de Oligonucleotídeos , Receptores Notch/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/fisiologiaRESUMO
Pathogens are considered to drive ecological and evolutionary dynamics of plant populations, but we lack data measuring the population-level consequences of infection in wild plant-pathogen interactions. Moreover, while it is often assumed that offseason environmental conditions drive seasonal declines in pathogen population size, little is known about how offseason environmental conditions impact the survival of pathogen resting stages, and how critical the offseason is for the next season's epidemic. The fungal pathogen Podosphaera plantaginis persists as a dynamic metapopulation in the large network of Plantago lanceolata host populations. Here, we analyze long-term data to measure the spatial synchrony of epidemics and consequences of infection for over 4000 host populations. Using a theoretical model, we study whether large-scale environmental change could synchronize disease occurrence across the metapopulation. During 2001-2013 exposure to freezing decreased, while pathogen extinction-colonization-persistence rates became more synchronized. Simulations of a theoretical model suggest that increasingly favorable winter conditions for pathogen survival could drive such synchronization. Our data also show that infection decreases host population growth. These results confirm that mild winter conditions increase pathogen overwintering success and thus increase disease prevalence across the metapopulation. Further, we conclude that the pathogen can drive host population growth in the Plantago-Podosphaera system.
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Ascomicetos/fisiologia , Interações Hospedeiro-Patógeno , Doenças das Plantas/microbiologia , Plantago/microbiologia , Estações do Ano , Modelos Lineares , Modelos Biológicos , Plantago/crescimento & desenvolvimento , Dinâmica PopulacionalRESUMO
In the open ocean, movements of migratory fish populations are typically surveyed using tagging methods that are subject to low sample sizes for archive tags, except for a few notable examples, and poor temporal resolution for conventional tags. Alternatively, one can infer patterns of movement of migratory fish by tracking movements of their predators, i.e., fishing vessels, whose navigational systems (e.g., GPS) provide accurate and frequent VMS (vessel monitoring system) records of movement in pursuit of prey. In this paper, we develop a state-space model that infers the foraging activities of fishing vessels from their tracks. Second, we link foraging activities to probabilities of tuna presence. Finally, using multivariate geostatistical interpolation (cokriging) we map the probability of tuna presence together with their estimation variances and produce a time series of indices of abundance. While the segmentation of the trajectories is validated by observers' data, the present VMS-index is compared to catch rate and proved to be useful for management perspectives. The approach reported in this manuscript extends beyond the case study considered. It can be applied to any foragers that engage in an attempt of capture when they see prey and for whom this attempt is linked to a tractable change in behavior.
Assuntos
Migração Animal , Comunicações Via Satélite , Navios , Atum/fisiologia , Animais , Meio Ambiente , Monitoramento Ambiental/instrumentação , Monitoramento Ambiental/métodos , Comportamento Predatório/fisiologia , Estações do Ano , Fatores de TempoRESUMO
Every year, millions of people experience intimate partner violence (IPV) and commercial sexual exploitation (CSE), with researchers increasingly discussing the overlap between these two forms of interpersonal violence. However, researchers have not yet used quantitative methods to examine the link between IPV and CSE or to explore potential mechanisms underlying the overlap, including child maltreatment risk factors and psychological mechanisms. One potential mechanism is trauma-related shame, a symptom of post-traumatic stress disorder commonly experienced by both victims of CSE and IPV. The current study explores trauma-related shame, childhood maltreatment, and IPV and their associations with CSE using a sample of 174 primarily Black women. Binomial logistic regression is used to analyze the impact of IPV, child abuse and neglect, and trauma-related shame on CSE. Results indicate that IPV and trauma-related shame are both significant predictors of CSE. Implications for future research and the incorporation of shame in trauma-related treatment are discussed.