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1.
Animal ; 18(2): 101051, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38199017

RESUMEN

Sustainable dairy and beef production provides environmental, economic, and social values that can potentially be maximized by optimizing herd management strategies. The length of a dairy cow's life is affected by, and affects, all three pillars of sustainability. Longevity in dairy cows is multifactorial and strongly dependent on herd management. Despite genetic improvements, the average time of culling for Swedish cows has barely changed and is currently at 2.6 lactations. This culling rate requires a high number of replacement heifers, generating high rearing costs for farmers. This study evaluated different herd management strategies to improve cow longevity and assessed the effects on enteric methane (CH4) emissions from the herd and the profitability of milk production and beef production from the dairy cows and their offspring. The base scenario, an average Swedish Holstein herd of 100 cows, was compared with seven scenarios simulated using a stochastic herd simulation model (SimHerd). Two of these scenarios involved improved health and survival of cows in the herd, three involved improved reproduction, one considered the consequences of keeping all surplus heifers in the herd, and one considered maximizing the use of X-sorted dairy semen and inseminating the rest of the herd with unsorted beef semen, to avoid surplus replacement heifers. Improved fertility had the greatest effect in increasing the productive life per cow, to 3.8 years compared with 2.8 in the base scenario, allowed for more use of beef semen, reduced the number of replacement heifers, and generated the highest herd profit (€98 per cow-year higher than base scenario). Keeping all surplus heifers instead of producing beef × dairy cross calves decreased the number of productive years by 0.8 and reduced profit by €22 per cow-year. The profit was highly associated with costs related to replacement heifers. The highest beef output (3 369 kg per year more than base scenario) was achieved by keeping all heifers and culling a high share of dairy cows, but this scenario also generated much higher enteric CH4 emissions (+1 257 kg per year). Improving health, survival, or fertility reduced enteric CH4 emissions by 90-255 kg per year, while total yearly beef production ranged from 59 kg less to 556 kg more than in the base scenario. Reducing the number of replacement heifers needed by improving cow reproductive performance is thus key to increasing cow longevity and profitability, while reducing enteric CH4 emissions from the herd without compromising milk and meat production.


Asunto(s)
Longevidad , Leche , Bovinos , Animales , Femenino , Granjas , Metano , Industria Lechera , Lactancia/genética
2.
J Dairy Sci ; 106(12): 8926-8941, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37678793

RESUMEN

The longevity of dairy cows is mainly determined by farmers' subjective culling decisions and can be linked to the environmental impact of dairy production and to the social acceptance of the industry. Still, the economic impacts of dairy cow longevity are not well understood. The aim of this study was to examine how herd average dairy cow longevity is related to the farm economic outcome. We used 3 indicators of economic outcome: technical efficiency, profitability, and average milk yield per cow. We used 2 indicators of dairy cow longevity: average herd length of life and average herd length of productive life. The study was based on a unique and detailed dataset from Swedish dairy agriculture, where herd-management data from the national dairy herd recording scheme were combined with farm-level economic variables from the Swedish Farm Accountancy Survey, for a total of 1,959 observations from 2010 to 2018. The regression results highlight that both measures of average herd dairy cow longevity have an overall positive and significant association with farm-level economic performance. These associations had an inverted U-shape, which implies that the association is first positive and then declines. Descriptive statistics indicate that the point where the maximum economic performance is attained varied across the economic indicators. Our results are relevant for individual dairy farmers and their advisors, who are interested in understanding how herd average longevity relates to economic performance on the farms. Our results are also important from a greater sustainability perspective, because linking them to previous knowledge about the environmental and social sustainability benefits of keeping cows longer highlights longevity-associated trade-offs between those benefits and the farm economic outcomes.


Asunto(s)
Industria Lechera , Longevidad , Femenino , Bovinos , Animales , Granjas , Suecia , Industria Lechera/métodos , Leche
3.
J Prev Alzheimers Dis ; 9(3): 480-490, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35841249

RESUMEN

BACKGROUND: Alzheimer's disease (AD) is a continuum of events beginning with an increase in brain soluble Aß42 followed by the appearance of hyperphosphorylated tau (P-tau, asymptomatic stage). Mild Cognitive Impairment (MCI) then appears (prodromal stage). However, the individual contribution of these two soluble proteins in the onset of the first cognitive symptoms remains unclear. OBJECTIVES: We sought to understand the specific impact of p-tau on the development of MCI in the AAV-AD rat model, a model of late-onset Alzheimer's disease (LOAD) predementia. METHODS: We specifically reduced the phosphorylation level of tau while leaving Aß42 levels unchanged using a DYRK1A protein kinase inhibitor, Leucettine L41, in an adeno-associated virus-based Alzheimer's disease (AAV-AD) rat model. Leucettine L41 was administered by intraperitoneal injection at 20 mg/kg per day in AAV-AD rats from 9 (late asymptomatic phase) to 10 (prodromal phase) months of age. RESULTS: Decreased soluble forms of P-tau induced by chronic administration of Leucettine L41 did not change soluble Aß42 levels but prevented MCI onset in 10-month-old AAV-AD rats. CONCLUSIONS: The present study argues that P-tau is required to induce the development of MCI. Consistent with our previous findings that soluble Aß42 is also required for MCI onset, the data obtained in the AAV-AD rat model confirm that the transition from the asymptomatic to the prodromal stage may be caused by the combined presence of both soluble brain forms of Aß42 and p-tau, suggesting that the development of MCI may be the consequence of their synergistic action.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Enfermedad de Alzheimer/diagnóstico , Péptidos beta-Amiloides , Animales , Disfunción Cognitiva/psicología , Humanos , Fragmentos de Péptidos , Síntomas Prodrómicos , Ratas , Proteínas tau/metabolismo
4.
Clin Exp Dermatol ; 47(5): 910-917, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34856000

RESUMEN

BACKGROUND: Basal cell carcinoma (BCC) is the most common type of cancer in fair-skinned individuals worldwide. Altered metabolism is a hallmark of cancer, and a growing body of evidence has shown increased expression of the large neutral amino acid transporter small subunit 1 (LAT1) in several types of cancers, including BCC. However, the mechanisms behind changed LAT1 expression in BCC are largely unknown. AIM: To describe the protein expression of LAT1 and its colocalization with LAT2, and to examine LAT1 in association with BCC tumour biology characteristics such as cell proliferation, apoptosis and hypoxia. METHODS: Immunofluorescence stains were used on formalin-fixed, paraffin-embedded tissue samples (n = 14) from excised BCCs, and their protein-staining patterns were examined. RESULTS: There was no correlation between expression of LAT1 and LAT2, and the colocalization was low. Compared with normal epidermis, there was significantly higher expression in BCC tissue of the proliferation markers topoisomerase IIα (P < 0.01) and Ki-67 (P = 0.01). The fraction of LAT1-expressing cells in BCC tissue was significantly (P < 0.01) inversely correlated with the fraction of proliferative active tumour cells. Cleaved caspase-3 was significantly (P = 0.02) increased in tumour areas with high LAT1 expression. CONCLUSIONS: The present study shows that LAT1 is not usually expressed by proliferating BCC cells. The morphological localization suggests that tumour cells use LAT1 to adapt to environmental changes such as starvation and/or hypoxia. These findings could have implications for future development of LAT1-inhibitory BCC treatments.


Asunto(s)
Carcinoma Basocelular , Transportador de Aminoácidos Neutros Grandes 1/metabolismo , Neoplasias Cutáneas , Carcinoma Basocelular/patología , Supervivencia Celular , Humanos , Hipoxia , Neoplasias Cutáneas/patología
5.
Nurse Educ Pract ; 55: 103169, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34388617

RESUMEN

AIM: The aim of the present study was to elucidate health-promoting and -impeding aspects of peer-learning by examining nursing students' descriptions of learning together as peers, and how this might interact with their health. BACKGROUND: Peer-learning is a useful strategy for teaching and learning in nursing students' clinical practice education. In the research, benefits such as improved cooperation and increased self-confidence have been described and labelled as health-promoting. DESIGN: A qualitative descriptive approach METHOD: Thirteen first-year nursing students aged 22-45 years, who had completed their first clinical practice education on a medical or surgical hospital ward, participated in one-on-one semi-structured interviews. The interviews were analyzed using qualitative content analysis. RESULT: Working as a pair was primarily described as positive, as the peers felt basic support from each other, even though they described negative experiences that limited their own development and challenged their patience. CONCLUSION: Peer-learning as a model for supervision in clinical practice incorporates valuable health-promoting aspects, as the students felt safe, supported, increased self-confidence, and participation. The interaction between peers helped them grow as human beings, and the mutual support the peers felt was a vital health-promoting aspect that limited the impact of the described health-impeding aspects, which included sometimes finding peer-learning trying, stressful and irritating.


Asunto(s)
Bachillerato en Enfermería , Educación en Enfermería , Estudiantes de Enfermería , Humanos , Aprendizaje , Grupo Paritario , Investigación Cualitativa
6.
Pathol Res Pract ; 216(10): 153151, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32853941

RESUMEN

Mixed epithelial and stromal tumor (MEST) of the kidney is a rare biphasic tumor composed of both stromal and epithelial components, the latter showing a variable proportion of solid to cystic areas. These tumors show a marked female predominance, commonly occur in perimenopausal age groups, and often have an ovarian-type stroma with ER and PR positivity, suggesting steroids may play a role in pathogenesis. Although typically benign, rare cases showing malignant transformation have been reported. We present a case of a 42-year-old man with a 10 cm right kidney mass located in the renal pelvis. Histologically, the majority of the tumor was composed of a diffuse, sheet-like growth of malignant cells demonstrating a rhabdoid morphology with large nuclei, prominent nucleoli, and eosinophilic eccentric cytoplasm. Brisk mitotic activity and coagulative type necrosis was also noted. Intimately associated with this malignant rhabdoid component was a much smaller portion of tumor featuring variably sized bland epithelial tubules embedded within a stroma composed of bland spindle cells and areas of hyalinization, diagnostic of MEST. By immunohistochemistry, the malignant rhabdoid tumor portion of the neoplasm showed complete loss of nuclear INI-1, while the MEST component retained nuclear expression of this antigen. With these features taken together, our case represents a malignant rhabdoid tumor arising in a background of MEST. To our knowledge, this case represents the first case of a MEST showing malignant transformation in the form of malignant rhabdoid tumor in a male patient in the English language literature.


Asunto(s)
Neoplasias Complejas y Mixtas/patología , Tumor Rabdoide/metabolismo , Neoplasias de los Tejidos Blandos/patología , Células del Estroma/patología , Carcinoma/patología , Humanos , Neoplasias Renales/patología , Masculino
7.
Child Psychiatry Hum Dev ; 51(5): 839-852, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32705460

RESUMEN

This randomized control trial used intent-to-treat analyses to compare parent management training-Oregon model (PMTO) (N = 64) to family-based services as usual (SAU) (N = 62) in 3.5-13-year-old children and their families in Denmark. Outcomes were parent report of child internalizing and externalizing problems, parenting efficacy, parenting stress, parent sense of coherence, parent-report of life satisfaction, and parental depressive symptoms. Outcomes were measured at pretreatment, post-treatment, and 18-20 months post-treatment. Results demonstrated that both PMTO and family-based SAU resulted in significant improvements in child externalizing and internalizing problems, parenting efficacy, as well as parent-reported stress and depressive symptoms, life satisfaction, and aspects of sense of cohesion. Effect sizes at post-treatment and follow-up were in the small to moderate range, consistent with prior PMTO evaluations. However, there were no significant differences between PMTO and family-based SAU. Further research on the process and content of family-based SAU is needed to determine how this approach overlaps with and is distinct from PMTO.


Asunto(s)
Conducta del Adolescente , Síntomas Conductuales/terapia , Conducta Infantil , Educación no Profesional , Terapia Familiar , Responsabilidad Parental , Adolescente , Niño , Preescolar , Dinamarca , Femenino , Humanos , Masculino , Problema de Conducta
8.
Geriatr Nurs ; 41(6): 790-803, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32522423

RESUMEN

OBJECTIVES: To evaluate the test-retest reliability and internal consistency of the Swedish version of the MAastrIcht Nurses Activities INventory (MAINtAIN(S)) developed to measure nursing staff perceived behaviours and barriers for promotion of everyday activities in nursing home residents. METHOD: Nursing staff completed the MAINtAIN(S) questionnaire on two occasions at 3-week intervals. Relative reliability, absolute reliability and internal consistency with Cronbach's alpha were calculated. RESULTS: The test--retest reliability of MAINtAIN(S)-behaviours subscales ranged from ICC2. = 0.78--0.91 and MAINtAIN(S)-barriers subscales from ICC2.1 = 0.60--0.84. Cronbach's alpha varied between 0.60 and 0.91 for the different subscales. The MAINtAIN(S) inventory shows acceptable reliability and internal consistency. MAINtAIN(S) seems to be a promising tool for identifying behaviours and barriers in promoting everyday activities in nursing home residents and can be used to develop ward specific interventions for promotion of daily physical activity level in the care of older adults.


Asunto(s)
Enfermeras y Enfermeros , Anciano , Humanos , Psicometría , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Suecia
9.
Infect Prev Pract ; 2(4): 100091, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34368725

RESUMEN

BACKGROUND: The wearing of gloves is included in the standard principles for preventing healthcare associated infections. A continued wearing of gloves may, however, result in the transmission of organisms instead of preventing infections. Few studies have explored how common it is for surfaces to be touched by potentially contaminated gloves. METHODS: Secondary analysis of field notes from 48 hours of unstructured observations of healthcare personnel's actions during patient care. The new focus was on to what extent healthcare personnel wore gloves that should have been removed or changed, what surfaces were touched by contaminated gloves and what patient-related activities were involved. RESULTS: A continued wearing of gloves occurred in about half of the observed episodes of patient care. On average, 3.3 surfaces were touched by contaminated gloves. The surfaces most frequently touched were 'unused single-use items', 'equipment controls/switches/regulators/flush buttons' and 'bed linen'. This occurred mostly while helping patients with 'personal hygiene', when performing 'test taking' or during procedures involving the operation of medical or other 'equipment'. CONCLUSION: The continued wearing of gloves during patient-related activities carries the risk of organism transmission, as the gloves touch many surfaces. The most critical moments seem to be when the use of gloves is considered essential. A better understanding of the motivators of improper glove-use behaviour is needed to develop interventions that rectify the improper use of gloves.

10.
Br J Dermatol ; 180(1): 130-140, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-29938775

RESUMEN

BACKGROUND: The incidence of basal cell carcinoma (BCC) is increasing and the costs for care rising. Therefore, the need for simplified and cost-effective treatment choices is substantial. Aberrant signalling in several pathways, induced by ultraviolet radiation, is of importance in the development of BCC. Alterations in tumour metabolic activity are part of general carcinogenesis; however, these alterations are only partially recognized in skin cancer. OBJECTIVES: To study expression profiles in BCCs compared with individually matched nontumour skin, with a focus on finding differences associated with tumour metabolism. MATERIALS AND METHODS: Gene expression in biopsies from BCCs (n = 14) compared with biopsies from nontumour gluteal skin was analysed with microarrays (n = 4 + 4) and/or quantitative real-time polymerase chain reaction (qPCR, n = 14 + 14). Protein expression and localization was assessed using immunohistochemistry (IHC) in formalin-fixed and paraffin-embedded BCC samples. RESULTS: Microarray analysis revealed increased expression of the amino acid transporters SLC7A5, SLC7A7 and SLC7A8 as well as the cytosolic enzyme tryptophan 2,3-dioxygenase (TDO) 2 in BCC. Higher expression of SLC7A5 (P < 0·001), SLC7A8 (P < 0·001) and TDO2 (P = 0·002), but not SLC7A7 (P = 0·50), was confirmed by qPCR, and IHC demonstrated correlating tumour cell protein expression of SLC7A5 and SLC7A8. Protein expression of SLC7A7 was observed in the stratum granulosum, and TDO2 in immune cells. CONCLUSIONS: This study highlights the upregulation of SLC7A5, SLC7A8 and TDO2 in BCC compared with nontumour skin. Our findings imply that amino acid transporters may be further explored as potential targets for future medical treatment.


Asunto(s)
Carcinoma Basocelular/patología , Neoplasias Cutáneas/patología , Anciano , Anciano de 80 o más Años , Sistema de Transporte de Aminoácidos y+/metabolismo , Sistema de Transporte de Aminoácidos y+L , Estudios de Cohortes , Femenino , Cadenas Ligeras de la Proteína-1 Reguladora de Fusión/metabolismo , Humanos , Transportador de Aminoácidos Neutros Grandes 1/metabolismo , Masculino , Persona de Mediana Edad , Piel/patología , Triptófano Oxigenasa/metabolismo , Regulación hacia Arriba
11.
Br J Dermatol ; 180(3): 559-564, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30339272

RESUMEN

BACKGROUND: Atopic dermatitis (AD) might adversely affect academic performance, possibly through influences on psychological functioning such as stress resilience. OBJECTIVES: To investigate the association of atopic dermatitis with stress resilience, cognitive function and educational attainment. METHODS: We used data from a national cohort of men who underwent a military conscription examination at ages 17-20 years in Sweden between 1969 and 1976. All potential conscripts met a physician who assessed current or previous history of AD. Stress resilience was measured by a psychologist using a semistructured interview. The conscription assessment included a written cognitive function test. The highest level of education achieved was identified through record linkage. RESULTS: The study population included 234 715 men, 1673 (0·7%) of whom had a diagnosis of AD. AD was associated with a greater risk of low stress resilience [adjusted relative risk ratio (RRR) 1·60, 95% confidence interval (CI) 1·38-1·86]. AD was associated with higher cognitive function (ß-coefficient 0·15, 95% CI 0·05-0·24) and higher educational level (RRR 1·29, 95% CI 1·13-1·47). However, adjustment for socioeconomic characteristics of the family of origin attenuated the magnitude of the associations and eliminated the statistical significance (ß-coefficient 0·06, 95% CI -0·03 to 0·15; RRR 1·16, 95% CI 1·00-1·35). CONCLUSIONS: Swedish men with AD had lower stress resilience in late adolescence but did not have lower cognitive function or poorer educational attainment. The lower stress resilience associated with AD is consistent with an increased risk of possible long-term adverse health outcomes.


Asunto(s)
Éxito Académico , Cognición , Dermatitis Atópica/psicología , Resiliencia Psicológica , Estrés Psicológico/psicología , Adolescente , Dermatitis Atópica/complicaciones , Dermatitis Atópica/epidemiología , Humanos , Masculino , Personal Militar/estadística & datos numéricos , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Factores Socioeconómicos , Estrés Psicológico/etiología , Suecia/epidemiología , Adulto Joven
12.
Radiat Prot Dosimetry ; 182(1): 80-84, 2018 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-30418654

RESUMEN

The acute radiation syndrome (ARS) constitutes the most challenging, immediate medical consequence of exposure to high doses of ionizing radiation in an emergency situation. This report highlights some of the currently available medical guidelines and recommendations on the clinical management of ARS, comments recent trends regarding the approval of targeted pharmaceuticals for ARS, and suggests further initiatives for international collaboration aiming at continuously updating the medical knowledge base of this syndrome.


Asunto(s)
Síndrome de Radiación Aguda/prevención & control , Cooperación Internacional , Exposición a la Radiación/efectos adversos , Radiación Ionizante , Síndrome de Radiación Aguda/etiología , Manejo de la Enfermedad , Humanos
13.
J Hosp Infect ; 100(3): e146-e150, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30081148

RESUMEN

BACKGROUND: To understand healthcare personnel's infection prevention behaviour has long been viewed as a key factor in preventing healthcare-associated infections. Suboptimal hand hygiene compliance and handling of materials, equipment, and surfaces present the main risks for potential organism transmission. Further exploration is needed regarding the role of context-specific conditions and the infection prevention behaviours of healthcare personnel. Such knowledge could enable the development of new intervention strategies for modifying behaviour. AIM: To describe risk behaviours for organism transmission in daily care activities over time. METHODS: Unstructured observations of healthcare personnel carrying out patient-related activities were performed on 12 occasions over a period of 18 months. FINDINGS: Risk behaviours for organism transmission occur frequently in daily care activities and the results show that the occurrence is somewhat stable over time. Interruptions in care activities contribute to an increased risk for organism transmission that could lead to subsequent healthcare-associated infection. CONCLUSION: Interventions aimed at reducing the risks of healthcare-associated infections need to focus on strategies that address: hand hygiene compliance; the handling of materials, equipment, work clothes and surfaces; the effects of interruptions in care activities if they are to alter healthcare personnel's infection prevention behaviour sufficiently.


Asunto(s)
Infección Hospitalaria/transmisión , Transmisión de Enfermedad Infecciosa , Personal de Salud , Asunción de Riesgos , Humanos , Estudios Longitudinales
14.
Br J Dermatol ; 176(2): 297-298, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-28244082
16.
Radiat Prot Dosimetry ; 171(1): 134-8, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27574328

RESUMEN

The triple disaster in March 2011 tragically and severely affected the Japanese society, in spite of its well-developed infrastructure and good access to resources. A multitude of Japanese and international reports have since described the chain of events and actions taken in connection with the earthquake, the tsunami and the power plant failure in Fukushima. In order to further evaluate Japanese experiences of the disaster, and to bring home 'lessons-learnt' of relevance for continued emergency preparedness planning, a group from the National Board of Health and Welfare and other Swedish agencies performed an observer visit to Japan in 2012. A report from the group was recently published. Its main conclusions, and implications focusing on a strengthened national medical preparedness for radionuclear events in Sweden (and possibly elsewhere), are presented here.


Asunto(s)
Defensa Civil , Planificación en Desastres/métodos , Accidente Nuclear de Fukushima , Desastres , Terremotos , Servicios Médicos de Urgencia , Programas de Gobierno , Humanos , Japón , Plantas de Energía Nuclear , Desarrollo de Programa , Traumatismos por Radiación , Suecia
18.
Oncogene ; 34(19): 2471-82, 2015 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-24998851

RESUMEN

Type II endometrial carcinomas (ECs) are estrogen independent, poorly differentiated tumors that behave in an aggressive manner. As TP53 mutation and CDH1 inactivation occur in 80% of human endometrial type II carcinomas, we hypothesized that mouse uteri lacking both Trp53 and Cdh1 would exhibit a phenotype indicative of neoplastic transformation. Mice with conditional ablation of Cdh1 and Trp53 (Cdh1(d/d)Trp53(d/d)) clearly demonstrate architectural features characteristic of type II ECs, including focal areas of papillary differentiation, protruding cytoplasm into the lumen (hobnailing) and severe nuclear atypia at 6 months of age. Further, Cdh1(d/d)Trp53(d/d) tumors in 12-month-old mice were highly aggressive, and metastasized to nearby and distant organs within the peritoneal cavity, such as abdominal lymph nodes, mesentery and peri-intestinal adipose tissues, demonstrating that tumorigenesis in this model proceeds through the universally recognized morphological intermediates associated with type II endometrial neoplasia. We also observed abundant cell proliferation and complex angiogenesis in the uteri of Cdh1(d/d)Trp53(d/d) mice. Our microarray analysis found that most of the genes differentially regulated in the uteri of Cdh1(d/d)Trp53(d/d) mice were involved in inflammatory responses. CD163 and Arg1, markers for tumor-associated macrophages, were also detected and increased in the uteri of Cdh1(d/d)Trp53(d/d) mice, suggesting that an inflammatory tumor microenvironment with immune cell recruitment is augmenting tumor development in Cdh1(d/d)Trp53(d/d) uteri. Further, inflammatory mediators secreted from CDH1-negative, TP53 mutant endometrial cancer cells induced normal macrophages to express inflammatory-related genes through activation of nuclear factor-κB signaling. These results indicate that absence of CDH1 and TP53 in endometrial cells initiates chronic inflammation, promotes tumor microenvironment development following the recruitment of macrophages and promotes aggressive ECs.


Asunto(s)
Proteínas Cdh1/genética , Neoplasias Endometriales/genética , Inflamación/genética , Macrófagos/inmunología , Proteína p53 Supresora de Tumor/genética , Animales , Antígenos CD/genética , Antígenos de Diferenciación Mielomonocítica/genética , Arginasa/genética , Línea Celular , Proliferación Celular/genética , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Neoplasias Endometriales/patología , Femenino , Humanos , Inflamación/inmunología , Inflamación/patología , Ratones , Ratones Noqueados , FN-kappa B/metabolismo , Neovascularización Patológica/genética , Receptores de Superficie Celular/genética , Microambiente Tumoral/inmunología , Útero/citología , Útero/patología
19.
Oncogene ; 34(26): 3452-62, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25174399

RESUMEN

We previously characterized the link between WNT7A and the progression of ovarian cancer. Other groups have identified FGF1 as a relevant risk factor in ovarian cancer. Here, we show a linkage between these two signaling pathways that may be exploited to improve treatment and prognosis of patients with ovarian cancer. High expression of WNT7A and FGF1 are correlated in ovarian carcinomas and poor overall patient survival. A chromatin immunoprecipitation assay demonstrated that WNT7A/ß-catenin signaling directly regulates FGF1 expression via TCF binding elements in the FGF1-1C promoter locus. In vitro gene manipulation studies revealed that FGF1 is sufficient to drive the tumor-promoting effects of WNT7A. In vivo xenograft studies confirmed that the stable overexpression of WNT7A or FGF1 induced a significant increase in tumor incidence, whereas FGF1 knockdown in WNT7A overexpressing cells caused a significant reduction in tumor size. Niclosamide most efficiently abrogated WNT7A/ß-catenin signaling in our model, inhibited ß-catenin transcriptional activity and cell viability, and increased cell death. Furthermore, niclosamide decreased cell migration following an increase in E-cadherin subsequent to decreased levels of SLUG. The effects of niclosamide on cell functions were more potent in WNT7A-overexpressing cells. Oral niclosamide inhibited tumor growth and progression in an intraperitoneal xenograft mouse model representative of human ovarian cancer. Collectively, these results indicate that FGF1 is a direct downstream target of WNT7A/ß-catenin signaling and this pathway has potential as a therapeutic target in ovarian cancer. Moreover, niclosamide is a promising inhibitor of this pathway and may have clinical relevance.


Asunto(s)
Resistencia a Antineoplásicos , Factor 1 de Crecimiento de Fibroblastos/genética , Niclosamida/farmacología , Neoplasias Ováricas , Proteínas Wnt/fisiología , beta Catenina/fisiología , Animales , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Células Cultivadas , Progresión de la Enfermedad , Resistencia a Antineoplásicos/genética , Femenino , Factor 1 de Crecimiento de Fibroblastos/metabolismo , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Vía de Señalización Wnt/fisiología
20.
Clin Auton Res ; 25(2): 87-94, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24743866

RESUMEN

PURPOSE: Orthostatic hypotension (OH) is common and increases with age. OH is part of the autonomic dysfunction in dementia with Lewy bodies (DLB). Commonly OH is diagnosed when the patient falls which is a risk factor of premature death. Our objective was to systematically investigate the clinical symptoms associated with measurement of OH in different neurodegenerative dementias and normal controls (NC). METHODS: 154 patients [50 DLB, 50 Alzheimer's disease (AD), 54 AD and vascular components (ADvasc)] were examined with systolic and diastolic blood pressure measurements in supine position, immediately after standing up and after 1, 3, 5 and 10 min of standing. They were compared with 50 NC. Orthostatic symptoms were registered according to a predefined protocol. RESULTS: Twenty-seven percent of all the investigated individuals reported OH symptoms during the measurement while 43% fulfilled the criteria of OH. Sixty-three percent of orthostatic patients did not have any symptoms during the measurement. The prevalence of any orthostatic symptoms during the measurement differed significantly (p < 0.001) between the diagnostic groups with 40% in DLB patients, 37% in ADvasc, 28% in AD and 2% in NC. The most frequent symptom was dizziness 13.7%. CONCLUSIONS: Classical orthostatic symptoms are absent in the majority of dementia patients with OH. The orthostatic reaction must therefore be routinely measured in this patient group. This is particularly important for patients with DLB where falls as a result of OH are common.


Asunto(s)
Demencia/complicaciones , Hipotensión Ortostática/complicaciones , Hipotensión Ortostática/epidemiología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Prevalencia
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