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1.
BMJ Open ; 13(5): e069664, 2023 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-37142309

RESUMEN

PURPOSE: The Swedish Tattoo and Body Modifications Cohort (TABOO) cohort was established to provide an infrastructure for epidemiological studies researching the role of tattoos and other body modifications as risk factors for adverse health outcomes. It is the first population-based cohort with detailed exposure assessment of decorative, cosmetic, and medical tattoos, piercing, scarification, henna tattoos, cosmetic laser treatments, hair dyeing, and sun habits. The level of detail in the exposure assessment of tattoos allows for investigation of crude dose-response relationships. PARTICIPANTS: The TABOO cohort includes 13 049 individuals that participated in a questionnaire survey conducted in 2021 (response rate 49%). Outcome data are retrieved from the National Patient Register, the National Prescribed Drug Register and the National Cause of Death Register. Participation in the registers is regulated by Swedish law, which eliminates the risk of loss to follow-up and associated selection bias. FINDINGS TO DATE: The tattoo prevalence in TABOO is 21%. The cohort is currently used to clarify the incidence of acute and long-lasting health complaints after tattooing based on self-reported data. Using register-based outcome data, we are investigating the role of tattoos as a risk factor for immune-mediated disease, including hypersensitisation, foreign body reactions and autoimmune conditions. FUTURE PLANS: The register linkage will be renewed every third year to update the outcome data, and we have ethical approval to reapproach the responders with additional questionnaires.


Asunto(s)
Baño de Sol , Tatuaje , Humanos , Tatuaje/efectos adversos , Tabú , Suecia/epidemiología , Encuestas y Cuestionarios
2.
Int Emerg Nurs ; 62: 101171, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35487042

RESUMEN

BACKGROUND: We know that ambulance staff may have sparse knowledge on how to comply with care approaches that ensure appropriate hygiene in the ambulance, but we do not know if and how the COVID-19 pandemic has affected ambulance staff's perceived compliance with hygiene routines. AIM: To investigate ambulance staff's self-reported hand hygiene (HH) perceptions and compliance; and to explore if and how the COVID-19 pandemic has affected ambulance staff's perceived compliance with hygiene routines. METHODS: A cross-sectional study design using the WHO-validated Perception Survey for Healthcare Workers regarding hygiene. Thematic analysis and descriptive statistics were used for analysis. RESULTS: 204 surveys were analysed, 92% of participants stated that their hygiene routine compliance had improved during the COVID-19 pandemic, and some participants also described that their colleagues' practice had improved. These improvements were reportedly driven by the need to acquire new knowledge to deal with the pandemic and sometimes with fear. CONCLUSIONS: Experience acquired during the pandemic needs to be sustainable if we are to increase HH and hygiene routine compliance in ambulance services. Interventions aimed at changing ambulance staff's perceived behaviour are warranted, and stakeholders should try and identify the personal motivations that lead these staff to seek self-betterment regarding HH and hygiene routine compliance. Otherwise, the risk of patients suffering from healthcare-associated infection may not decrease as wished.


Asunto(s)
COVID-19 , Higiene de las Manos , Ambulancias , COVID-19/prevención & control , Estudios Transversales , Adhesión a Directriz , Humanos , Pandemias
3.
Photochem Photobiol Sci ; 20(2): 285-292, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33721253

RESUMEN

In prospective observational cohort studies, increasing sun exposure habits have been associated with reduced risk of cardiovascular mortality. Our aim was to assess possible observational mechanisms for this phenomenon. A written questionnaire was answered by 23,593 women in the year 2000 regarding risk factors for melanoma, including factors of possible interest for hypertension, such as detailed sun exposure habits, hypertension, marital status, education, smoking, alcohol consumption, BMI, exercise, and chronic high stress. Hypertension was measured by the proxy "use of hypertension medication" 2005-2007, and high stress by "need of anti-depressive medication". Sun exposure habits was assessed by the number of `yes' to the following questions; Do you sunbath during summer?, During winter vacation?, Do you travel south to sunbath?, Or do you use sun bed? Women answering 'yes' on one or two questions had moderate and those answering 'yes' on three or four as having greatest sun exposure. The main outcome was the risk of hypertension by sun exposure habits adjusted for confounding. As compared to those women with the greatest sun exposure, women with low and moderate sun exposure were at 41% and 15% higher odds of hypertension (OR 1.41, 95% CI 1.3‒1.6, p < 0.001 and OR 1.15, 95% CI 1.1‒1.2, p < 0.001), respectively. There was a strong age-related increased risk of hypertension. Other risk factors for hypertension were lack of exercise (OR 1.36), a non-fair phenotype (OR 1.08), chronic high stress level (OR 1.8), and lack of university education (OR 1.3). We conclude that in our observational design sun exposure was associated with a dose-dependent reduced risk of hypertension, which might partly explain the fewer deaths of cardiovascular disease with increasing sun exposure.


Asunto(s)
Hipertensión/diagnóstico , Baño de Sol/estadística & datos numéricos , Adulto , Anciano , Índice de Masa Corporal , Estudios de Cohortes , Escolaridad , Ejercicio Físico , Femenino , Humanos , Hipertensión/epidemiología , Hipertensión/patología , Persona de Mediana Edad , Oportunidad Relativa , Estudios Prospectivos , Factores de Riesgo , Estaciones del Año , Estrés Psicológico , Encuestas y Cuestionarios
5.
Br J Surg ; 104(3): 278-287, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27802358

RESUMEN

BACKGROUND: Many patients with rectal cancer receive radiotherapy (RT) to reduce the risk of local recurrence. Radiation may give rise to adverse effects, including second primary cancers. In view of the divergent results of previous studies, the present study evaluated the risk of second primary cancer following RT in all randomized RT rectal cancer trials conducted in Sweden and in the Swedish ColoRectal Cancer Registry (SCRCR). METHODS: Patients included in five randomized trials and the SCRCR were linked to the Swedish Cancer Registry. Cox regression models estimated the hazard ratio (HR) of second primary cancer among patients who received RT compared with those who did not. RESULTS: A total of 13 457 patients were included in this study; 7024 (52·2 per cent) received RT and 6433 (47·8 per cent) had surgery alone. Overall, no increased risk of second primary cancer was observed with RT (HR 1·03; 95 per cent c.i. 0·92 to 1·15), independently of follow-up time and location within or outside of the irradiated volume. In the randomized trials, with longer follow-up (maximum 31 years), a slight increase was observed outside of (HR 1·33, 1·01 to 1·74) but not within (HR 1·11, 0·73 to 1·67) the irradiated volume. Irradiated men had a lower risk of prostate cancer than those treated with surgery alone (HR 0·68, 0·51 to 0·91). CONCLUSION: Overall, there was no increased risk of second primary cancer following RT for rectal cancer within or outside of the irradiated volume up to 20 years of follow-up. Men with rectal cancer who received RT had a reduced risk of prostate cancer.


Asunto(s)
Adenocarcinoma/radioterapia , Neoplasias Inducidas por Radiación/etiología , Neoplasias Primarias Secundarias/etiología , Neoplasias del Recto/radioterapia , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Inducidas por Radiación/diagnóstico , Neoplasias Inducidas por Radiación/epidemiología , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias Primarias Secundarias/epidemiología , Modelos de Riesgos Proporcionales , Radioterapia Adyuvante , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias del Recto/cirugía , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Suecia
6.
J Intern Med ; 281(2): 219-220, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27443452
7.
Clin Exp Allergy ; 46(6): 803-12, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27228571

RESUMEN

BACKGROUND: Asthma is common in both children and adults in the Western world, just like anxiety and depression. While some research has revealed that these diseases might share important environmental and pathophysiological aspects, the exact mechanisms still remain unclear. OBJECTIVE: To study the correlation firstly between depression or anxiety and asthma diagnosis in adult twins and secondly the association between parental depression or anxiety and offspring asthma in children of twins. METHODS: In total, 24 685 adult twins aged 20-47 years were interviewed or completed a Web-based questionnaire and their children were identified through the Multi-Generation Register. Asthma diagnosis was obtained from the Patient Register and the Prescribed Drug Register. Assessment of depression and anxiety was obtained from questionnaires using Center for Epidemiologic Studies Depression Scale (CES-D), major depression and generalized anxiety disorder (GAD) from DSM-IV. The association between depression or anxiety and asthma was analyzed with logistic regression adjusting for confounders in twins and offspring. To address genetic and familial environmental confounding, we performed a cotwin analysis using disease-discordant twin pairs. RESULTS: We found an association between asthma and CES-D, major depression and GAD, for example adjusted OR for major depression and register-based asthma 1.56 (1.36-1.79). Most of the point estimates remained in the co-twin control analysis, indicating that the association was likely not due to genetic or familial environmental factors. There was no association between parental depression and/or anxiety and asthma diagnosis in the offspring which implies lack of genetic confounding. CONCLUSIONS: We found an association between own asthma diagnosis and anxiety or depression, but not with offspring asthma. Our results indicate that the associations were not due to confounding from genes or environment shared by the twins.


Asunto(s)
Ansiedad/epidemiología , Ansiedad/etiología , Asma/complicaciones , Asma/epidemiología , Depresión/epidemiología , Depresión/etiología , Gemelos , Adulto , Asma/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Vigilancia de la Población , Prevalencia , Factores de Riesgo , Encuestas y Cuestionarios , Suecia/epidemiología , Adulto Joven
8.
Eur J Cancer Care (Engl) ; 25(5): 744-52, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27028409

RESUMEN

The aim of this population-based registry study was to explore how cancer influences the health of partners, by examining the onset of new diagnoses for partners, health care use and health care costs among partners living with patients with cancer. The sample consisted of partners of patients with cancer (N = 10 353) and partners of age- and sex-matched controls who did not have cancer (N = 74 592). Diagnoses, health care use and health care costs were studied for a continuous period starting 1 year before the date of cancer diagnosis and continued for 3 years. One year after cancer diagnosis, partners of patients with cancer had significantly more mood disorders, reactions to severe stress and ischaemic heart disease than they exhibited in the year before the diagnosis. Among partners of patients with cancer, the type of cancer was associated with the extent and form of increased health care use and costs; both health care use and costs increased among partners of patients with liver cancer, lung cancer, colon cancer and miscellaneous other cancers. The risk of poorer health varied according to the type of cancer diagnosed, and appeared related to the severity and prognosis of that diagnosis.


Asunto(s)
Estado de Salud , Neoplasias/psicología , Parejas Sexuales/psicología , Adulto , Anciano , Atención Ambulatoria/estadística & datos numéricos , Estudios de Casos y Controles , Femenino , Costos de la Atención en Salud , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Humor/etiología , Neoplasias/diagnóstico , Neoplasias/epidemiología , Aceptación de la Atención de Salud/estadística & datos numéricos , Pronóstico , Sistema de Registros , Estrés Psicológico/etiología , Suecia/epidemiología
9.
J Intern Med ; 280(4): 375-87, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-26992108

RESUMEN

OBJECTIVE: Women with active sunlight exposure habits experience a lower mortality rate than women who avoid sun exposure; however, they are at an increased risk of skin cancer. We aimed to explore the differences in main causes of death according to sun exposure. METHODS: We assessed the differences in sun exposure as a risk factor for all-cause mortality in a competing risk scenario for 29 518 Swedish women in a prospective 20-year follow-up of the Melanoma in Southern Sweden (MISS) cohort. Women were recruited from 1990 to 1992 (aged 25-64 years at the start of the study). We obtained detailed information at baseline on sun exposure habits and potential confounders. The data were analysed using modern survival statistics. RESULTS: Women with active sun exposure habits were mainly at a lower risk of cardiovascular disease (CVD) and noncancer/non-CVD death as compared to those who avoided sun exposure. As a result of their increased survival, the relative contribution of cancer death increased in these women. Nonsmokers who avoided sun exposure had a life expectancy similar to smokers in the highest sun exposure group, indicating that avoidance of sun exposure is a risk factor for death of a similar magnitude as smoking. Compared to the highest sun exposure group, life expectancy of avoiders of sun exposure was reduced by 0.6-2.1 years. CONCLUSION: The longer life expectancy amongst women with active sun exposure habits was related to a decrease in CVD and noncancer/non-CVD mortality, causing the relative contribution of death due to cancer to increase.


Asunto(s)
Causas de Muerte , Luz Solar , Adulto , Enfermedades Cardiovasculares/mortalidad , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Esperanza de Vida , Melanoma/prevención & control , Persona de Mediana Edad , Neoplasias/mortalidad , Factores de Riesgo , Neoplasias Cutáneas/prevención & control , Luz Solar/efectos adversos , Suecia
10.
Br J Surg ; 103(5): 513-23, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26856820

RESUMEN

BACKGROUND: Diagnosis by screening mammography is considered an independent positive prognostic factor, although the data are not fully in agreement. The aim of the study was to explore whether the mode of detection (screening-detected versus symptomatic) adds prognostic information to the St Gallen molecular subtypes of primary breast cancer, in terms of 10-year cumulative breast cancer mortality (BCM). METHODS: A prospective cohort of patients with primary breast cancer, who had regularly been invited to screening mammography, were included. Tissue microarrays were constructed from primary tumours and lymph node metastases, and evaluated by two independent pathologists. Primary tumours and lymph node metastases were classified into St Gallen molecular subtypes. Cause of death was retrieved from the Central Statistics Office. RESULTS: A total of 434 patients with primary breast cancer were included in the study. Some 370 primary tumours and 111 lymph node metastases were classified into St Gallen molecular subtypes. The luminal A-like subtype was more common among the screening-detected primary tumours (P = 0·035) and corresponding lymph node metastases (P = 0·114) than among symptomatic cancers. Patients with screening-detected tumours had a lower BCM (P = 0·017), and for those diagnosed with luminal A-like tumours the 10-year cumulative BCM was 3 per cent. For patients with luminal A-like lymph node metastases, there was no BCM. In a stepwise multivariable analysis, the prognostic information yielded by screening detection was hampered by stage and tumour biology. CONCLUSION: The prognosis was excellent for patients within the screening programme who were diagnosed with a luminal A-like primary tumour and/or lymph node metastases. Stage, molecular pathology and mode of detection help to define patients at low risk of death from breast cancer.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Lobular/diagnóstico , Detección Precoz del Cáncer , Mamografía , Anciano , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/mortalidad , Carcinoma Lobular/metabolismo , Carcinoma Lobular/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Análisis de Matrices Tisulares
11.
Br J Dermatol ; 174(1): 95-103, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26333521

RESUMEN

BACKGROUND: Risk of basal cell carcinoma (BCC) has been reported to be several-fold increased among organ transplant recipients (OTRs). However, due to lack of reliable BCC registration, population-based risk estimates are scarce. OBJECTIVES: To characterize risk of BCC among OTRs compared with the general population, and contrast with risk of cutaneous squamous cell carcinoma (SCC). SUBJECTS AND METHODS: OTRs transplanted during 2004-2011 were identified through national healthcare registers and linked with the nationwide Swedish BCC Register initialized in 2004. Relative risk of BCC was expressed as standardized incidence ratios (SIR) with 95% confidence intervals (CI). RESULTS: Altogether, 4023 transplanted patients developed 341 BCCs during follow-up. Compared with the general population, the relative risk of BCC was increased sixfold (SIR 6·1, 95% CI 5·4-6·9). The risk was higher in kidney and heart/lung than in liver recipients (SIRkidney 7·2, 6·3-8·3; SIRheart/lung 5·8, 4·0-8·2; SIRliver 2·6, 1·7-4·0), and risk increased with time since transplantation (Ptrend < 0·01). The SCC to BCC ratio was 1 : 1·7 and BCC developed earlier after transplantation than SCC. Distribution of anatomical sites and histological types did not differ substantially between OTR- and population-BCCs. CONCLUSIONS: Risk of BCC was strikingly elevated in OTRs compared with the general population. Risk was higher in kidney recipients and increased with follow-up time. These findings support a tumour-promoting effect of immunosuppressive drugs in BCC development. The low SCC to BCC ratio was possibly attributed to short follow-up time.


Asunto(s)
Carcinoma Basocelular/epidemiología , Trasplante de Órganos/efectos adversos , Neoplasias Cutáneas/epidemiología , Receptores de Trasplantes/estadística & datos numéricos , Adulto , Distribución por Edad , Anciano , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Trasplante de Órganos/estadística & datos numéricos , Estudios Prospectivos , Factores de Riesgo , Distribución por Sexo , Suecia/epidemiología
12.
Phys Chem Chem Phys ; 17(16): 11014-9, 2015 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-25823890

RESUMEN

In this report we investigate the self-discharge in a positively charged polypyrrole-cellulose composite material in water solution. Rate constants for the self-discharge reaction are determined by potential step methods and their dependence on pH, temperature and applied potential are reported. Based on the results, we propose that two fundamentally different self-discharge mechanisms operate in parallel; one of faradaic origin with a rate constant increasing exponentially with applied potential and one mechanism comprising an initial reaction of the charged polymer with hydroxide ions. The second mechanism dominates at high pH as the rate constant for this reaction increases exponentially with pH whilst the faradaic reaction dominates at low pH. With this report we hope to shed light on the complex and elusive nature of self-discharge in conducting polymers to serve as guidance for the construction of electrical energy storage devices with conducting polymer components.


Asunto(s)
Polímeros/química , Pirroles/química , Agua/química , Celulosa/química , Electroquímica , Concentración de Iones de Hidrógeno , Cinética , Soluciones , Temperatura
13.
Ann Rheum Dis ; 74(2): 354-60, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24285495

RESUMEN

OBJECTIVE: To compare drug survival on adalimumab, etanercept and infliximab in patients with rheumatoid arthritis (RA). METHODS: Patients with RA (n=9139; 76% women; mean age 56 years) starting their first tumour necrosis factor (TNF) inhibitor between 2003 and 2011 were identified in the Swedish Biologics Register (ARTIS). Data were collected through 31 December 2011. Drug survival over up to 5 years of follow-up was compared overall and by period of treatment start (2003-2005/2006-2009; n=3168/4184) with adjustment for age, sex, education, period, health assessment questionnaire (HAQ), disease duration, concomitant disease modifying antirheumatic drug (DMARD) treatment and general frailty (using hospitalisation history as proxy). RESULTS: During 20 198 person-years (mean/median 2.2/1.7 years) of follow-up, 3782 patients discontinued their first biological (19/100 person-years; 51% due to inefficacy, 36% due to adverse events). Compared with etanercept, infliximab (adjusted HR 1.63, 95% CI 1.51 to 1.77) and adalimumab initiators had higher discontinuation rates (1.26, 95% CI 1.16 to 1.37), and infliximab had a higher discontinuation rate than adalimumab (1.28, 95% CI 1.18 to 1.40). These findings were consistent across periods, but were modified by time for adalimumab versus etanercept (p<0.001; between-drug difference highest the 1st year in both periods). The discontinuation rate was higher for starters in 2006-2009 than 2003-2005 (adjusted HR 1.12, 95% CI 1.04 to 1.20). The composition of 1-year discontinuations also changed from 2003-2005 vs 2006-2009: adverse events decreased from 45% to 35%, while inefficacy increased from 43% to 53% (p<0.001). CONCLUSIONS: Discontinuation rates were higher for infliximab compared with adalimumab and etanercept initiators, and for adalimumab versus etanercept during the 1st year. Discontinuation rates increased with calendar period, as did the percentage discontinuations due to inefficacy.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Inmunoglobulina G/uso terapéutico , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Adalimumab , Anciano , Etanercept , Femenino , Humanos , Infliximab , Masculino , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores
14.
J Intern Med ; 276(1): 77-86, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24697969

RESUMEN

BACKGROUND: Sunlight exposure and fair skin are major determinants of human vitamin D production, but they are also risk factors for cutaneous malignant melanoma (MM). There is epidemiological evidence that all-cause mortality is related to low vitamin D levels. METHODS: We assessed the avoidance of sun exposure as a risk factor for all-cause mortality for 29 518 Swedish women in a prospective 20-year follow-up of the Melanoma in Southern Sweden (MISS) cohort. Women were recruited from 1990 to 1992 and were aged 25 to 64 years at the start of the study. We obtained detailed information at baseline on their sun exposure habits and potential confounders. Multivariable flexible parametric survival analysis was applied to the data. RESULTS: There were 2545 deaths amongst the 29 518 women who responded to the initial questionnaire. We found that all-cause mortality was inversely related to sun exposure habits. The mortality rate amongst avoiders of sun exposure was approximately twofold higher compared with the highest sun exposure group, resulting in excess mortality with a population attributable risk of 3%. CONCLUSION: The results of this study provide observational evidence that avoiding sun exposure is a risk factor for all-cause mortality. Following sun exposure advice that is very restrictive in countries with low solar intensity might in fact be harmful to women's health.


Asunto(s)
Causas de Muerte , Exposición a Riesgos Ambientales , Baño de Sol , Luz Solar , Adulto , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Femenino , Humanos , Melanoma/etiología , Melanoma/mortalidad , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Conducta de Reducción del Riesgo , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/mortalidad , Factores Socioeconómicos , Baño de Sol/psicología , Baño de Sol/estadística & datos numéricos , Luz Solar/efectos adversos , Suecia/epidemiología , Vitamina D/metabolismo
15.
PLoS Genet ; 9(9): e1003713, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24068942

RESUMEN

Growth factor independent 1 (Gfi1) is a transcriptional repressor originally identified as a gene activated in T-cell leukemias induced by Moloney-murine-leukemia virus infection. Notch1 is a transmembrane receptor that is frequently mutated in human T-cell acute lymphoblastic leukemia (T-ALL). Gfi1 is an important factor in the initiation and maintenance of lymphoid leukemias and its deficiency significantly impedes Notch dependent initiation of T-ALL in animal models. Here, we show that immature hematopoietic cells require Gfi1 to competently integrate Notch-activated signaling. Notch1 activation coupled with Gfi1 deficiency early in T-lineage specification leads to a dramatic loss of T-cells, whereas activation in later stages leaves development unaffected. In Gfi1 deficient multipotent precursors, Notch activation induces lethality and is cell autonomous. Further, without Gfi1, multipotent progenitors do not maintain Notch1-activated global expression profiles typical for T-lineage precursors. In agreement with this, we find that both lymphoid-primed multipotent progenitors (LMPP) and early T lineage progenitors (ETP) do not properly form or function in Gfi1(-/-) mice. These defects correlate with an inability of Gfi1(-/-) progenitors to activate lymphoid genes, including IL7R, Rag1, Flt3 and Notch1. Our data indicate that Gfi1 is required for hematopoietic precursors to withstand Notch1 activation and to maintain Notch1 dependent transcriptional programming to determine early T-lymphoid lineage identity.


Asunto(s)
Proteínas de Unión al ADN/genética , Receptor Notch1/genética , Transducción de Señal/genética , Linfocitos T/citología , Factores de Transcripción/genética , Animales , Linaje de la Célula , Regulación Leucémica de la Expresión Génica/inmunología , Redes Reguladoras de Genes , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Humanos , Linfocitos/citología , Linfocitos/metabolismo , Ratones , Linfocitos T/inmunología
16.
Br J Dermatol ; 169(5): 1049-55, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23855428

RESUMEN

BACKGROUND: BRAF and NRAS mutations are frequently found in melanoma tumours, and recently developed BRAF-targeted therapies demonstrate significant clinical benefit. OBJECTIVES: We sought to investigate the clinical significance of BRAF and NRAS mutations in a clinic-based metastatic melanoma cohort. METHODS: In total, 237 tumours, mostly metastatic lesions, from 203 patients were screened for mutations in exon 15 of BRAF and exon 2 of NRAS using Sanger sequencing. BRAF and NRAS mutation status was analysed in relation to clinical and histopathological characteristics, and outcome. RESULTS: Mutation in BRAF and NRAS was present in 43% (88% V600E, 10% V600K) and 30% (48% Q61K, 40% Q61R) of metastatic melanomas, respectively. We found consistent BRAF and NRAS mutation status in all but one of 27 patients with multiple metastases. BRAF mutation was associated with younger age at primary diagnosis (P = 0.02). Among patients with distant metastatic melanoma, patients with BRAF-mutant tumours without BRAF inhibitor treatment had inferior survival compared with patients with BRAF inhibitor treatment [hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.10-5.01, P = 0.03]. We also observed a trend towards better prognosis for patients with wild-type and NRAS-mutant tumours compared with BRAF V600E-mutant tumours (HR 0.64, 95% CI 0.39-1.04, P = 0.07; and HR 0.76, 95% CI 0.48-1.21, P = 0.25, respectively). CONCLUSIONS: We were able to confirm the effect of BRAF inhibitor treatment in a single clinical institution. The results suggest further that BRAF mutation is a weak prognostic factor but a strong predictive factor and that BRAF-mutant melanoma might constitute one or more distinct subtypes of the disease with certain aetiology and clinical outcome.


Asunto(s)
GTP Fosfohidrolasas/genética , Genes ras , Melanoma/genética , Proteínas de la Membrana/genética , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias Cutáneas/genética , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Supervivencia sin Enfermedad , Exones , Femenino , Humanos , Indoles/uso terapéutico , Masculino , Melanoma/tratamiento farmacológico , Melanoma/cirugía , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/genética , Pronóstico , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/cirugía , Sulfonamidas/uso terapéutico , Vemurafenib
17.
Br J Surg ; 100(8): 1100-7, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23696510

RESUMEN

BACKGROUND: Evaluating the external validity of clinical trials requires knowledge not only of the study population but also of a relevant reference population. The main aim of this study was to present data from a large, contemporary, population-based cohort of patients with colonic cancer. METHODS: Data on patients diagnosed between 2007 and 2011 were extracted from the Swedish Colon Cancer Registry. The data, registered prospectively in a national population of almost 10 million, included over 99 per cent of all diagnosed adenocarcinomas of the colon. RESULTS: This analysis included 18,889 patients with 19,526 tumours (3·0 per cent had synchronous tumours). The sex distribution was fairly equal, and the median age was 74·1 (interquartile range 65-81) years. The overall and relative (cancer-specific) survival rates after 3 years were 62·7 and 71·4 per cent respectively. Some 88·0 per cent of the patients were operated on, and 83·8 per cent had tumours resected. Median blood loss during bowel resection was 200 (mean 311) ml, and the median operating time was 160 min; 5·6 per cent of the procedures were laparoscopic. Preoperative chemotherapy was administered to 2·1 per cent of patients; postoperative chemotherapy was planned in 90·1 per cent of fit patients aged less than 75 years with stage III disease. In patients operated on in an emergency setting (21·5 per cent), the preoperative evaluation was less extensive, the proportion of R0 resections was lower, and the outcomes were poorer, in both the short and long term. CONCLUSION: These population-based data represent good-quality reference points.


Asunto(s)
Adenocarcinoma/cirugía , Neoplasias del Colon/cirugía , Adenocarcinoma/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Neoplasias del Colon/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Análisis de Supervivencia , Suecia/epidemiología
18.
Nat Commun ; 4: 1660, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23552075

RESUMEN

Krüppel-like factor 5 regulates pluripotent stem cell self-renewal, but its role in somatic stem cells is unknown. Here we show that Krüppel-like factor 5-deficient haematopoietic stem cells and progenitors fail to engraft after transplantation. This haematopoietic stem cell and progenitor defect is associated with impaired bone marrow homing and lodging and decreased retention in bone marrow, and with decreased adhesion to fibronectin and expression of membrane-bound ß1/ß2-integrins. In vivo-inducible gain-of-function of Krüppel-like factor 5 in haematopoietic stem cells increases haematopoietic stem cell and progenitor adhesion. The expression of Rab5 family members, mediators of ß1/ß2-integrin recycling in the early endosome, is decreased in Klf5(Δ/Δ) haematopoietic stem cells and progenitors. Krüppel-like factor 5 binds directly to the promoter of Rab5a/b, and overexpression of Rab5b rescues the expression of activated ß1/ß2-integrins, adhesion and bone marrow homing of Klf5(Δ/Δ) haematopoietic stem cells and progenitors. Altogether, these data indicate that Krüppel-like factor 5 is indispensable for adhesion, homing, lodging and retention of haematopoietic stem cells and progenitors in the bone marrow through Rab5-dependent post-translational regulation of ß1/ß2 integrins.


Asunto(s)
Células de la Médula Ósea/citología , Antígenos CD18/metabolismo , Integrina beta1/metabolismo , Factores de Transcripción de Tipo Kruppel/fisiología , Células Madre/citología , Proteínas de Unión al GTP rab5/metabolismo , Animales , Adhesión Celular , Fibronectinas/metabolismo , Ratones , Ratones Endogámicos C57BL , Transporte de Proteínas , ARN Mensajero/genética , Proteínas de Unión al GTP rab5/genética
19.
J Dev Orig Health Dis ; 3(6): 442-9, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25084297

RESUMEN

There is some evidence that perinatal factors, specifically birth weight (BW), may be related to the onset of prostate cancer (PRCA). This case-control study, nested within the Malmö Diet and Cancer Cohort Study, used archived birth record data from 308 incident PRCA cases diagnosed between 1991 and 2005, and 637 age-matched controls among 4781 men born (1923-1945) in Malmö and Lund, Sweden. We applied conditional logistic regression to examine the birth size-PRCA association, including tumour subtypes, adjusting for perinatal and adult factors. Compared with controls, cases had a non-significantly higher mean BW and were more likely to have high (>4000 g) BW (21% v. 18%), but did not differ in other birth size measures, nor in mean adult body mass index . We observed a non-linear association between BW and PRCA risk. Compared with BWs between 3000 and 3500 g (reference), the fully adjusted odds ratios (OR, 95% CI) were 0.55 (0.33-0.91) for <3000 g, 0.86 (0.61-1.22) for 3500-4000 g and 0.98 (0.64-1.50) for >4000 g. Among men with aggressive tumours, the reduction in risk for those with BWs <3000 g (OR 0.26, 95% CI 0.09-0.72) was stronger than the rate of risk for PRCA overall. Crude risk estimates were minimally attenuated when adjusted for gestational age, maternal age, birth order and adult factors. Birth length, head circumference and placental weight were not associated with prostate cancer. Our results indicate a protective effect of lower BW on risk of total and aggressive prostate cancer, rather than any direct effect of larger birth size.


Asunto(s)
Peso al Nacer , Neoplasias de la Próstata/etiología , Estatura , Índice de Masa Corporal , Estudios de Casos y Controles , Conducta Alimentaria , Humanos , Modelos Logísticos , Masculino , Riesgo , Clase Social , Suecia
20.
Eur J Oncol Nurs ; 15(5): 390-7, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21163701

RESUMEN

PURPOSE: To investigate how life situation by persons with advanced colorectal cancer and their partners is affected by living with the disease and its treatment. METHOD: Separate, individual interviews were made with persons with advanced colorectal cancer (n = 12) and their partners (n = 9) about how their daily lives were affected by the disease and its treatment. The verbatim transcripts were analysed using content analysis. RESULTS: Living with the illness of advanced colorectal cancer was experienced to be: being inside or outside the healthcare system, striving for normality and becoming conscious of life's value and vulnerability. Living as a partner was experienced as living in an altered relation and as living in the shadow of the disease. CONCLUSIONS: When one in a partner relation suffers from colorectal cancer, it changes life and life perspective for both partners. Partners need to be invited to and involved in the care. Cancer nursing should focus on supporting the strive for normality in daily life, as the disease and its' treatment may last for a longer period of time. Supporting the partner may benefit the person with cancer as well, to cope along the illness trajectory.


Asunto(s)
Adaptación Psicológica , Actitud Frente a la Salud , Neoplasias Colorrectales/psicología , Acontecimientos que Cambian la Vida , Esposos/psicología , Adulto , Anciano , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Femenino , Humanos , Relaciones Interpersonales , Masculino , Persona de Mediana Edad , Investigación Metodológica en Enfermería , Investigación Cualitativa , Calidad de Vida/psicología
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