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1.
Glob Chang Biol ; 30(3): e17235, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38497525

RESUMEN

The accelerating pace of climate change has led to unprecedented shifts in surface temperature and precipitation patterns worldwide, with African savannas being among the most vulnerable regions. Understanding the impacts of these extreme changes on ecosystem health, functioning and stability is crucial. This paper focuses on the detection of breakpoints, indicative of shifts in ecosystem functioning, while also determining relevant ecosystem characteristics and climatic drivers that increase susceptibility to these shifts within the semi-arid to arid savanna biome. Utilising a remote sensing change detection approach and rain use efficiency (RaUE) as a proxy for ecosystem functioning, spatial and temporal patterns of breakpoints in the savanna biome were identified. We then employed a novel combination of survival analysis and remote sensing time series analysis to compare ecosystem characteristics and climatic drivers in areas experiencing breakpoints versus areas with stable ecosystem functioning. Key ecosystem factors increasing savanna breakpoint susceptibility were identified, namely higher soil sand content, flatter terrain and a cooler long-term mean temperature during the wet summer season. Moreover, the primary driver of changes in ecosystem functioning in arid savannas, as opposed to wetter tropical savannas, was found to be the increased frequency and severity of rainfall events, rather than drought pressures. This research highlights the importance of incorporating wetness severity metrics alongside drought metrics to comprehensively understand climate-ecosystem interactions leading to abrupt shifts in ecosystem functioning in arid biomes. The findings also emphasise the need to consider the underlying ecosystem characteristics, including soil, topography and vegetation composition, in assessing ecosystem responses to climate change. While this research primarily concentrated on the southern African savanna as a case study, the methodological robustness of this approach enables its application to diverse arid and semi-arid biomes for the assessment of climate-ecosystem interactions that contribute to abrupt shifts.


Asunto(s)
Ecosistema , Pradera , Lluvia , Estaciones del Año , Suelo
2.
Front Immunol ; 13: 1066359, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36591246

RESUMEN

Immune checkpoint inhibitors, including anti-PD-1 and anti-CTLA-4 therapies, are used to (re)activate the immune system to treat cancer. Despite promising results, a large group of patients does not respond to checkpoint inhibition. In the vulnerability-stress model of behavioral medicine, behavioral factors, such as stress, exercise and classical pharmacological conditioning, predict cancer incidence, recurrence and the efficacy of conventional cancer treatments. Given the important role of the immune system in these processes, certain behavior may be promising to complement immune checkpoint inhibition therapy. Here, we discuss the preliminary evidence and suitability of three behavioral mechanisms, i.e. stress modulation, exercise and classical pharmacological conditioning for the benefit of immunotherapy. It is crucial to study the potential beneficial effects of behavioral strategies that support immunotherapeutic anti-tumor effects with rigorous experimental evidence, to exploit behavioral mechanisms in improving checkpoint inhibition efficacy.


Asunto(s)
Neoplasias , Humanos , Neoplasias/terapia , Inmunoterapia/métodos
3.
Int J Hyg Environ Health ; 237: 113811, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34311418

RESUMEN

Legionnaires Disease incidence has risen in the Netherlands in recent years. For the majority of the cases, the source of infection is never identified. Two Dutch wastewater treatment plants (WWTPs) have previously been identified as source of outbreaks of Legionnaires Disease (LD) among local residents. The objective of this study is to examine if LD patients in the Netherlands are more exposed to aerosols originating from WWTPs than controls. METHODS: An atmospheric dispersion model was used to generate nationwide exposure maps of aerosols from 776 WWTPs in the Netherlands. Municipal sewage treatment plants and industrial WWTPs were both included. Exposure of LD cases and controls at the residential address was compared, in a matched case-control design using a conditional logistic regression. Cases were notified LD cases with onset of disease in the period 2013-2018 in the Netherlands (n = 1604). RESULTS: Aerosols dispersed over a large part of the Netherlands, but modelled concentrations are estimated to be elevated in close proximity to WWTPs. A statistically significant association was found between LD and the calculated annual average aerosol concentrations originating from WWTPs (odds-ratio: 1.32 (1.06-1.63)). This association remained significant when the two outbreak-related WWTPs were removed from the analysis (odds-ratio: 1.28 (1.03-1.58)). CONCLUSION: LD cases were more exposed to aerosols from WWTPs than controls. This indicates that exposure to aerosols dispersed from WWTPs caused Legionnaires Disease in residents living near WWTPs in the period 2013-2018. In order to investigate which characteristics of WWTPs are associated with an increased LD risk, the WWTP database should be updated and more data is needed on the presence and survival of aerosolized Legionella bacteria to improve the Legionella dispersion modelling. Furthermore, it is recommended to further investigate how aerosol dispersion of WWTPs can effectively be reduced in order to reduce the potential health risk.


Asunto(s)
Legionella pneumophila , Legionella , Enfermedad de los Legionarios , Purificación del Agua , Estudios de Casos y Controles , Brotes de Enfermedades , Humanos , Enfermedad de los Legionarios/epidemiología
4.
BMC Cancer ; 20(1): 850, 2020 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-32887573

RESUMEN

BACKGROUND: There are profound individual differences in clinical outcomes between colorectal cancers (CRCs) presenting with identical stage of disease. Molecular stratification, in conjunction with the traditional TNM staging, is a promising way to predict patient outcomes. We investigated the interconnectivity between tumor stage and tumor biology reflected by the Consensus Molecular Subtypes (CMSs) in CRC, and explored the possible value of these insights in patients with stage II colon cancer. METHODS: We performed a retrospective analysis using clinical records and gene expression profiling in a meta-cohort of 1040 CRC patients. The interconnectivity of tumor biology and disease stage was assessed by investigating the association between CMSs and TNM classification. In order to validate the clinical applicability of our findings we employed a meta-cohort of 197 stage II colon cancers. RESULTS: CMS4 was significantly more prevalent in advanced stages of disease (stage I 9.8% versus stage IV 38.5%, p < 0.001). The observed differential gene expression between cancer stages is at least partly explained by the biological differences as reflected by CMS subtypes. Gene signatures for stage III-IV and CMS4 were highly correlated (r = 0.77, p < 0.001). CMS4 cancers showed an increased progression rate to more advanced stages (CMS4 compared to CMS2: 1.25, 95% CI: 1.08-1.46). Patients with a CMS4 cancer had worse survival in the high-risk stage II tumors compared to the total stage II cohort (5-year DFS 41.7% versus 100.0%, p = 0.008). CONCLUSIONS: Considerable interconnectivity between tumor biology and tumor stage in CRC exists. This implies that the TNM stage, in addition to the stage of progression, might also reflect distinct biological disease entities. These insights can potentially be utilized to optimize identification of high-risk stage II colon cancers.


Asunto(s)
Neoplasias del Colon/genética , Neoplasias del Colon/patología , Transcriptoma , Anciano , Supervivencia sin Enfermedad , Femenino , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Masculino , Inestabilidad de Microsatélites , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Riesgo
5.
PLoS One ; 14(6): e0218956, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31247003

RESUMEN

Various models and datasets related to aflatoxins in the maize and dairy production chain have been developed and used but they have not yet been linked with each other. This study aimed to investigate the impacts of climate change on aflatoxin B1 production in maize and its consequences on aflatoxin M1 contamination in dairy cow's milk, using a full chain modelling approach. To this end, available models and input data were chained together in a modelling framework. As a case study, we focused on maize grown in Eastern Europe and imported to the Netherlands to be fed-as part of dairy cows' compound feed-to dairy cows in the Netherlands. Three different climate models, one aflatoxin B1 prediction model and five different carryover models were used. For this particular case study of East European maize, most of the calculations suggest an increase (up to 50%) of maximum mean aflatoxin M1 in milk by 2030, except for one climate (DMI) model suggesting a decrease. Results from all combinations of carryover and climate models suggest a similar or slight increase (up to 0.6%) of the chance of finding aflatoxin M1 in milk above the EC limit of 0.05 µg/kg by 2030. Results varied mainly with the climate model data and carryover model considered. The model framework infrastructure is flexible so that forecasting models for other mycotoxins or other food safety hazards as well as other production chains, together with necessary input databases, can easily be included as well. This modelling framework for the first time links datasets and models related to aflatoxin B1 in maize and related aflatoxin M1 the dairy production chain to obtain a unique predictive methodology based on Monte Carlo simulation. Such an integrated approach with scenario analysis provides possibilities for policy makers and risk managers to study the effects of changes in the beginning of the chain on the end product.


Asunto(s)
Aflatoxina B1/análisis , Aflatoxina M1/análisis , Leche/química , Zea mays/crecimiento & desarrollo , Alimentación Animal/análisis , Animales , Cambio Climático , Europa Oriental , Contaminación de Alimentos/análisis , Especies Introducidas , Modelos Teóricos , Países Bajos , Zea mays/química
6.
S Afr J Surg ; 56(3): 47-50, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30264943

RESUMEN

BACKGROUND: We investigated the prevalence of HIV and human papilloma virus (HPV) infection in men with penile carcinoma. METHODS: This retrospective study investigated all men with penile carcinoma at the Universitas Academic Hospital in Bloemfontein, South Africa (January 2000-December 2008). Patients' age, HIV status, histological type of carcinoma and evidence of HPV infection were recorded. Statistical analyses included Student's t-test and Fisher's exact test where appropriate (2-tailed p-value < 0.05 indicated statistical significant). RESULTS: Among 65 patients (mean age 50.9 years, range 37-69), the most common histological type was squamous cell carcinoma (80.0%). HIV status was known for 48 patients; 27 (56.2%) were HIV-positive. The mean age at presentation was 43.7 years (range 26-69) years in the HIV-positive and 57.2 years (range 26-89) years in the HIV-negative group. Approximately 55% of HIV-positive and 24% of HIV-negative patients showed histological evidence of HPV infection (p = 0.04). No significant difference was found with regard to histological type of carcinoma. CONCLUSION: Patients with penile carcinoma had a high prevalence of HIV infection. The HIV-positive group were significantly younger at presentation, with a higher prevalence of HPV infection, suggesting that HIV may contribute to HPV-associated penile cancer at a younger age.


Asunto(s)
Carcinoma de Células Escamosas/patología , Infecciones por VIH/epidemiología , Neoplasias del Pene/epidemiología , Neoplasias del Pene/patología , Adulto , Distribución por Edad , Anciano , Biopsia con Aguja , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/terapia , Causalidad , Estudios de Cohortes , Comorbilidad , Estudios de Seguimiento , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Hospitales Universitarios , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasias del Pene/terapia , Prevalencia , Estudios Retrospectivos , Medición de Riesgo , Sudáfrica
7.
S. Afr. j. surg. (Online) ; 56(3): 47-50, 2018. ilus
Artículo en Inglés | AIM (África) | ID: biblio-1271028

RESUMEN

Background: We investigated the prevalence of HIV and human papilloma virus (HPV) infection in men with penile carcinoma.Method: This retrospective study investigated all men with penile carcinoma at the Universitas Academic Hospital in Bloemfontein, South Africa (January 2000­December 2008). Patients' age, HIV status, histological type of carcinoma and evidence of HPV infection were recorded. Statistical analyses included Student's t-test and Fisher's exact test where appropriate (2-tailed p-value < 0.05 indicated statistical significant).Results: Among 65 patients (mean age 50.9 years, range 37­69), the most common histological type was squamous cell carcinoma (80.0%). HIV status was known for 48 patients; 27 (56.2%) were HIV-positive. The mean age at presentation was 43.7 years (range 26­69) years in the HIV-positive and 57.2 years (range 26­89) years in the HIV-negative group. Approximately 55% of HIV-positive and 24% of HIV-negative patients showed histological evidence of HPV infection (p = 0.04). No significant difference was found with regard to histological type of carcinoma.Conclusion: Patients with penile carcinoma had a high prevalence of HIV infection. The HIV-positive group were significantly younger at presentation, with a higher prevalence of HPV infection, suggesting that HIV may contribute to HPV-associated penile cancer at a younger age


Asunto(s)
Carcinoma , Pene , Sudáfrica
8.
Br J Anaesth ; 119(2): 231-238, 2017 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-28854530

RESUMEN

BACKGROUND: Checklists can reduce medical errors. However, the effectiveness of checklists is hampered by lack of acceptance and compliance. Recently, a new type of checklist with dynamic properties has been created to provide more specific checklist items for each individual patient. Our purpose in this simulation-based study was to investigate a newly developed intelligent dynamic clinical checklist (DCC) for the intensive care unit (ICU) ward round. METHODS: Eligible clinicians were invited to participate as volunteers. Highest achievable scores were established for six typical ICU scenarios to determine which items must be checked. The participants compared the DCC with the local standard of care. The primary outcomes were the caregiver satisfaction score and the percentages of checked items overall and of critical items requiring a direct intervention. RESULTS: In total, 20 participants were included, who performed 116 scenarios. The median percentage of checked items was 100.0% with the DCC and 73.6% for the scenarios completed with local standard of care ( P <0.001). Critical items remained unchecked in 23.1% of the scenarios performed with local standard of care and 0.0% of the scenarios where the DCC was available ( P <0.001). The mean satisfaction score of the DCC was 4.13 out of 5. CONCLUSIONS: This simulation study indicates that an intelligent DCC significantly increases compliance with best practice by reducing the percentage of unchecked items during ICU ward rounds, while the user satisfaction rate remains high. Real-life clinical research is required to evaluate this new type of checklist further.


Asunto(s)
Lista de Verificación , Unidades de Cuidados Intensivos , Adulto , Anciano , Estudios Cruzados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Satisfacción Personal , Estudios Prospectivos
9.
Oncogenesis ; 6(7): e357, 2017 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-28692036

RESUMEN

The recent discovery of 'molecular subtypes' in human primary colorectal cancer has revealed correlations between subtype, propensity to metastasize and response to therapy. It is currently not known whether the molecular tumor subtype is maintained after distant spread. If this is the case, molecular subtyping of the primary tumor could guide subtype-targeted therapy of metastatic disease. In this study, we classified paired samples of primary colorectal carcinomas and their corresponding liver metastases (n=129) as epithelial-like or mesenchymal-like, using a recently developed immunohistochemistry-based classification tool. We observed considerable discordance (45%) in the classification of primary tumors and their liver metastases. Discordant classification was significantly associated with the use of neoadjuvant chemotherapy. Furthermore, gene expression analysis of chemotherapy-exposed versus chemotherapy naive liver metastases revealed expression of a mesenchymal program in pre-treated tumors. To explore whether chemotherapy could cause gene expression changes influencing molecular subtyping, we exposed patient-derived colonospheres to six short cycles of 5-fluorouracil. Gene expression profiling and signature enrichment analysis subsequently revealed that the expression of signatures identifying mesenchymal-like tumors was strongly increased in chemotherapy-exposed tumor cultures. Unsupervised clustering of large cohorts of human colon tumors with the chemotherapy-induced gene expression program identified a poor prognosis mesenchymal-like subgroup. We conclude that neoadjuvant chemotherapy induces a mesenchymal phenotype in residual tumor cells and that this may influence the molecular classification of colorectal tumors.

11.
J Anim Sci ; 94(10): 4360-4368, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27898873

RESUMEN

Today, early weaning is more frequently applied by the modern pig breeder to obtain more litters per year. In addition, more and more European pig breeders apply a batch management system, which allows weaning to occur at fixed time points but entails that the offspring are treated at the litter level and not as individuals. Both evolutions might result in weaning lightweight piglets, which can cause, e.g., growth retardation of the offspring. Hence, the objective of this research was to improve the weaning weight of piglets of the same age by breeding with a highly conformed sire line. Therefore, a total of 23 sows were inseminated, 10 sows with semen of a well-conformed sire line (sire line B) and 13 sows with semen of a less conformed boar (sire line A). In total, 299 offspring were observed to monitor behavior, growth performance, and carcass characteristics. Subsequently, linear mixed models were developed to analyze the growth performance and carcass characteristics wherein only variables classified as significant ( < 0.05) were introduced as fixed factors. Results indicate that no significantly increased weaning weight could be accomplished by breeding with semen of sire line B. This could be due to the significant ( < 0.05) shorter gestation length of sows inseminated with semen of sire line B. However, the offspring of sire line B was defined by better carcass classification characteristics. Furthermore, this study presents that the mean birth weight of each piglet was significantly lower if a bigger litter size was recorded. When considering behavior, it was observed that piglets that did not seclude themselves from the litter had a significantly greater daily weight gain from birth to weaning compared to piglets that showed signs of isolation from the litter. A significantly greater daily gain from birth to slaughter was established for piglets with a greater birth weight. Also, results indicate that barrows had a significantly greater daily growth from weaning to slaughter than gilts. To conclude, this research determines that breeding with highly conformed sire lines does not improve the weaning weight of the offspring and thus cannot serve as a solution for early weaning. However, more research is required by performing more experiments with a greater number of boars and sows to confirm this result. In general, this study allows researchers to continue to improve and standardize the weaning weight of piglets of the same age.


Asunto(s)
Composición Corporal/genética , Porcinos/genética , Aumento de Peso/genética , Animales , Cruzamiento , Femenino , Masculino , Porcinos/crecimiento & desarrollo
12.
Oncogene ; 35(46): 6026-6037, 2016 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-27157610

RESUMEN

Colorectal cancer (CRC) is a heterogeneous disease posing a challenge for accurate classification and treatment of this malignancy. There is no common genetic molecular feature that would allow for the identification of patients at risk for developing recurrences and thus selecting patients who would benefit from more stringent therapies still poses a major clinical challenge. Recently, an international multicenter consortium (CRC Subtyping Consortium) was established aiming at the classification of CRC patients in biologically homogeneous CRC subtypes. Four consensus molecular subtypes (CMSs) were identified, of which the mesenchymal CMS4 presented with worse prognosis signifying the importance of identifying these patients. Despite the large number of samples analyzed and their clear association with unifying biological programs and clinical features, single-driver mutations could not be identified and patients are heterogeneous with regard to currently used clinical markers. We therefore set out to define the regulatory mechanisms underlying the distinct gene expression profiles using a network-based approach involving multiple molecular modalities such as gene expression, methylation levels and microRNA (miR) expression. The miR-200 family presented as the most powerful determinant of CMS4-specific gene expression, tuning the majority of genes differentially expressed in the poor prognosis subtype, including genes associated with the epithelial-mesenchymal transition program. Furthermore, our data show that two epigenetic marks, namely the methylation of the two miR-200 promoter regions, can identify tumors belonging to the mesenchymal subtype and is predictive of disease-free survival in CRC patients. Importantly, epigenetic silencing of the miR-200 family is also detected in epithelial CRC cell lines that belong to the mesenchymal CMS. We thus show that determining regulatory networks is a powerful strategy to define drivers of distinct cancer subtypes, which possess the ability to identify subtype affiliation and to shed light on biological behavior.


Asunto(s)
Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , MicroARNs/genética , Línea Celular Tumoral , Neoplasias Colorrectales/mortalidad , Biología Computacional/métodos , Metilación de ADN , Epigénesis Genética , Femenino , Humanos , Masculino , Familia de Multigenes , Fenotipo , Pronóstico , Regiones Promotoras Genéticas , Transcriptoma
13.
Oncogene ; 35(40): 5263-5271, 2016 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-26996663

RESUMEN

Gene expression-based classification systems have identified an aggressive colon cancer subtype with mesenchymal features, possibly reflecting epithelial-to-mesenchymal transition (EMT) of tumor cells. However, stromal fibroblasts contribute extensively to the mesenchymal phenotype of aggressive colon tumors, challenging the notion of tumor EMT. To separately study the neoplastic and stromal compartments of colon tumors, we have generated a stroma gene filter (SGF). Comparative analysis of stromahigh and stromalow tumors shows that the neoplastic cells in stromahigh tumors express specific EMT drivers (ZEB2, TWIST1, TWIST2) and that 98% of differentially expressed genes are strongly correlated with them. Analysis of differential gene expression between mesenchymal and epithelial cancer cell lines revealed that hepatocyte nuclear factor 4α (HNF4α), a transcriptional activator of intestinal (epithelial) differentiation, and its target genes are highly expressed in epithelial cancer cell lines. However, mesenchymal-type cancer cell lines expressed only part of the mesenchymal genes expressed by tumor-derived neoplastic cells, suggesting that external cues were lacking. We found that collagen-I dominates the extracellular matrix in aggressive colon cancer. Mimicking the tumor microenvironment by replacing laminin-rich Matrigel with collagen-I was sufficient to induce tumor-specific mesenchymal gene expression, suppression of HNF4α and its target genes, and collective tumor cell invasion of patient-derived colon tumor organoids. The data connect collagen-rich stroma to mesenchymal gene expression in neoplastic cells and to collective tumor cell invasion. Targeting the tumor-collagen interface may therefore be explored as a novel strategy in the treatment of aggressive colon cancer.


Asunto(s)
Neoplasias del Colon/genética , Transición Epitelial-Mesenquimal/genética , Factor Nuclear 4 del Hepatocito/genética , Microambiente Tumoral/genética , Diferenciación Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Colágeno/genética , Colágeno/metabolismo , Neoplasias del Colon/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Células del Estroma/metabolismo , Células del Estroma/patología
14.
Meat Sci ; 116: 86-90, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26874086

RESUMEN

This study investigates the relationship between sound levels, pre-slaughter handling during loading and pork quality. Pre-slaughter variables were investigated from loading till slaughter. A total of 3213 pigs were measured 30 min post-mortem for pH(30LT) (M. Longissimus thoracis). First, a sound level model for the risk to develop PSE meat was established. The difference in maximum and mean sound level during loading, mean sound level during lairage and mean sound level prior to stunning remained significant within the model. This indicated that sound levels during loading had a significant added value to former sound models. Moreover, this study completed the global classification checklist (Vermeulen et al., 2015a) by developing a linear mixed model for pH(30LT) and PSE prevalence, with the difference in maximum and mean sound level measured during loading, the feed withdrawal period and the difference in temperature during loading and lairage. Hence, this study provided new insights over previous research where loading procedures were not included.


Asunto(s)
Crianza de Animales Domésticos , Carne/normas , Sonido/efectos adversos , Porcinos/fisiología , Transportes , Mataderos , Bienestar del Animal , Animales , Estrés Fisiológico
15.
Oncogene ; 35(32): 4179-87, 2016 08 11.
Artículo en Inglés | MEDLINE | ID: mdl-26751771

RESUMEN

CFTR, the cystic fibrosis (CF) gene, encodes for the CFTR protein that plays an essential role in anion regulation and tissue homeostasis of various epithelia. In the gastrointestinal (GI) tract CFTR promotes chloride and bicarbonate secretion, playing an essential role in ion and acid-base homeostasis. Cftr has been identified as a candidate driver gene for colorectal cancer (CRC) in several Sleeping Beauty DNA transposon-based forward genetic screens in mice. Further, recent epidemiological and clinical studies indicate that CF patients are at high risk for developing tumors in the colon. To investigate the effects of CFTR dysregulation on GI cancer, we generated Apc(Min) mice that carried an intestinal-specific knockout of Cftr. Our results indicate that Cftr is a tumor suppressor gene in the intestinal tract as Cftr mutant mice developed significantly more tumors in the colon and the entire small intestine. In Apc(+/+) mice aged to ~1 year, Cftr deficiency alone caused the development of intestinal tumors in >60% of mice. Colon organoid formation was significantly increased in organoids created from Cftr mutant mice compared with wild-type controls, suggesting a potential role of Cftr in regulating the intestinal stem cell compartment. Microarray data from the Cftr-deficient colon and the small intestine identified dysregulated genes that belong to groups of immune response, ion channel, intestinal stem cell and other growth signaling regulators. These associated clusters of genes were confirmed by pathway analysis using Ingenuity Pathway Analysis and gene set enrichment analysis (GSEA). We also conducted RNA Seq analysis of tumors from Apc(+/+) Cftr knockout mice and identified sets of genes dysregulated in tumors including altered Wnt ß-catenin target genes. Finally we analyzed expression of CFTR in early stage human CRC patients stratified by risk of recurrence and found that loss of expression of CFTR was significantly associated with poor disease-free survival.


Asunto(s)
Neoplasias Colorrectales/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Genes Supresores de Tumor , Animales , Colon/metabolismo , Colon/patología , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Eliminación de Gen , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Mutación , Transducción de Señal
16.
Meat Sci ; 108: 106-8, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26072730

RESUMEN

Lung lesions of about 1000 pigs (nN) were scored in the slaughter line. Carcass weight, back fat thickness, loin muscle depth, pHi and PQMi were measured on 460 pigs. Twenty-four hours after slaughter pHu, PQMu, brightness, redness, yellowness and drip loss were measured on 59 carcasses. A score for lung lesions was assessed at batch level, based on observations of all pigs in that batch, i.e. about 130. Pigs systematically selected from batches scoring more than 25% lung lesions had a lower pH of LD muscle (P≤0.0003) and a six fold higher risk for P(ale)S(oft)E(xudative) traits (P≤0.050) compared to batches scoring less than 5%.


Asunto(s)
Calidad de los Alimentos , Enfermedades Pulmonares/veterinaria , Carne/análisis , Animales , Concentración de Iones de Hidrógeno , Masculino , Músculo Esquelético/metabolismo , Factores de Riesgo , Porcinos
17.
Meat Sci ; 105: 53-6, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25805321

RESUMEN

This study investigates whether rectal temperature of pigs, prior to slaughter, can give an indication of the risk of developing pork with PSE characteristics. A total of 1203 pigs were examined, measuring the rectal temperature just before stunning, of which 794 rectal temperatures were measured immediately after stunning. pH30LT (M. Longissimus thoracis) and temperature of the ham (Temp30Ham) were collected from about 530 carcasses, 30 min after sticking. The results present a significant positive linear correlation between rectal temperature just before and after slaughter, and Temp30Ham. Moreover, pH30LT is negatively correlated with rectal temperature and Temp30Ham. Finally, a linear mixed model for pH30LT was established with the rectal temperature of the pigs just before stunning and the lairage time. This model defines that measuring rectal temperature of pigs just before slaughter allows discovery of pork with PSE traits, taking into account pre-slaughter conditions.


Asunto(s)
Regulación de la Temperatura Corporal , Calidad de los Alimentos , Carne/análisis , Músculo Esquelético/química , Estrés Fisiológico , Estrés Psicológico/diagnóstico , Sus scrofa/fisiología , Mataderos , Crianza de Animales Domésticos/métodos , Animales , Bélgica , Temperatura Corporal , Cruzamientos Genéticos , Concentración de Iones de Hidrógeno , Modelos Lineales , Músculo Esquelético/metabolismo , Recto , Estrés Psicológico/metabolismo , Estrés Psicológico/fisiopatología , Estrés Psicológico/prevención & control , Sus scrofa/psicología , Factores de Tiempo , Transportes
18.
Ann Cardiol Angeiol (Paris) ; 64(2): 63-7, 2015 Apr.
Artículo en Francés | MEDLINE | ID: mdl-25702240

RESUMEN

UNLABELLED: Clinically discovering a systolic murmur is frequent among the young military population. When this murmur does not sound benign, a transthoracic echocardiography (TTE) is made to detect any cardiopathy, which could cause sudden cardiac death. The aim of this study was to evaluate the interest of systematic TTE in the assessment of any cardiac systolic murmur (CSM) among militaries. METHODS: We ran a retrospective monocentric study in the "Clermont-Tonnerre" military hospital in Brest. We included all patients sent for TEE, aged 15 to 30 years old, from the 1st January 2010 until the 31st July 2013. RESULTS: Two hundred and eighty TTES assessing CSM were performed. We found 28/280 (10%) echocardiographic abnormalities: 13 were bicuspid aortic valves (4.6%), 6 were ventricular septal defects (2.15%), 3 were atrial septal defects (1.07%), 4 were mild mitral regurgitations (1.43%), one mild pulmonary stenosis (0.35%) and one aortic stenosis (0.35%). No hypertrophic cardiomyopathy was found. Concerning military expertise, 11 (3.92%) patients among these 28 with abnormal TEE were considered unfit for work or "fit for work with limitations". CONCLUSION: Assessing a cardiac systolic murmur with TEE lead to the diagnosis of a cardiomyopathy in 10% of the case. This study enhances the importance of systematic TEE when a CSM is detected in the young military, in order to determine if those soldiers can still fulfill their military duty.


Asunto(s)
Ecocardiografía , Cardiopatías/complicaciones , Cardiopatías/diagnóstico por imagen , Medicina Militar , Personal Militar , Soplos Sistólicos/diagnóstico por imagen , Soplos Sistólicos/etiología , Adolescente , Adulto , Válvula Aórtica/anomalías , Válvula Aórtica/diagnóstico por imagen , Enfermedad de la Válvula Aórtica Bicúspide , Diagnóstico Diferencial , Ecocardiografía/métodos , Femenino , Francia/epidemiología , Auscultación Cardíaca , Cardiopatías/epidemiología , Defectos del Tabique Interatrial/diagnóstico por imagen , Defectos del Tabique Interventricular/diagnóstico por imagen , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Humanos , Masculino , Personal Militar/estadística & datos numéricos , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Palpación , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sensibilidad y Especificidad
19.
Meat Sci ; 100: 118-23, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25460114

RESUMEN

Environmental variables, as sound levels, were collected during the pre-slaughter process in 18 different Belgian commercial slaughterhouses. Four pre-slaughter phases were determined: firstly after arrival of the truck at the slaughterhouse and just before unloading, secondly during unloading, thirdly at lairage and finally while moving to the stunner. A total of 8508 pigs was examined during the pre-slaughter process, of which the pH(LT) (M. longissimus thoracis), at 30 min post-mortem was measured. For each pre-slaughter phase, variables which might influence pork quality were determined. Moreover, this study made it possible to infer a checklist to represent and predict PSE traits of pork for all kind of pre-slaughter situations. The checklist shows also that the impact on pork quality is more decisive for the variables measured close to the stunning phase. Hence, this information is useful for the industry to optimize handling of pigs, reducing the risk for PSE traits.


Asunto(s)
Mataderos , Bienestar del Animal , Calidad de los Alimentos , Carne/análisis , Estrés Fisiológico , Estrés Psicológico , Animales , Lista de Verificación , Ambiente , Humanos , Concentración de Iones de Hidrógeno , Carne/normas , Músculo Esquelético , Cambios Post Mortem , Porcinos
20.
Meat Sci ; 100: 269-74, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25460136

RESUMEN

This study investigates whether sound levels above 85 dB(A), determined in literature as a critical sound level to induce stress in pigs, has also an effect on the pH of pork. Sound levels were recorded during pre-slaughter phases. A measure was taken after the arrival of the truck at the slaughterhouse, during unloading, lairage and just before stunning. The pH of the Longissimus thoracis or lumborum, 30 min after sticking (pH(30LT)) was measured. 8508 pigs were examined and the pH was measured on the carcasses. The results show that the cut-off value of 85 dB(A) during the pre-slaughtering phase is not only a threshold to evaluate animal welfare but can also be associated with a slower drop of pH if sound levels are b85 dB(A). Finally a linear mixed model for pH(30LT) was built with the sound level during lairage and the sound level prior to stunning as independent variables, having statistically the highest impact on pH(30LT) of pork.


Asunto(s)
Mataderos , Bienestar del Animal , Carne/análisis , Ruido , Estrés Fisiológico , Animales , Humanos , Concentración de Iones de Hidrógeno , Carne/normas , Músculo Esquelético , Porcinos
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