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X-ray free-electron lasers (XFELs) deliver pulses of coherent X-rays on the femtosecond time scale, with potentially high repetition rates. While XFELs provide high peak intensities, both the intensity and the centroid of the beam fluctuate strongly on a pulse-to-pulse basis, motivating high-rate beam diagnostics that operate over a large dynamic range. The fast drift velocity, low X-ray absorption and high radiation tolerance properties of chemical vapour deposition diamonds make these crystals a promising candidate material for developing a fast (multi-GHz) pass-through diagnostic for the next generation of XFELs. A new approach to the design of a diamond sensor signal path is presented, along with associated characterization studies performed in the XPP endstation of the LINAC Coherent Light Source (LCLS) at SLAC. Qualitative charge collection profiles (collected charge versus time) are presented and compared with those from a commercially available detector. Quantitative results on the charge collection efficiency and signal collection times are presented over a range of approximately four orders of magnitude in the generated electron-hole plasma density.
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The red blood cell (RBC) antigen Wra is a low-prevalence antigen first described in 1953 by Holman and assigned to the Diego system in 1995. Because of its low prevalence, Wra is usually absent on commercial screening RBCs and antibody identification panels. When Wr(a+) screening RBCs are available, the corresponding antibody, anti-Wra, is often found in sera from healthy individuals, patients, and pregnant women. Anti-Wra can cause both hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. We describe a fatal acute hemolytic transfusion reaction caused by anti-Wra in a patient with no other RBC alloantibodies. Serologic investigation showed that one of the RBC units the patient received was Wr(a+). Immunohematology 2021;37:20-24.The red blood cell (RBC) antigen Wra is a low-prevalence antigen first described in 1953 by Holman and assigned to the Diego system in 1995. Because of its low prevalence, Wra is usually absent on commercial screening RBCs and antibody identification panels. When Wr(a+) screening RBCs are available, the corresponding antibody, anti-Wra, is often found in sera from healthy individuals, patients, and pregnant women. Anti-Wra can cause both hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. We describe a fatal acute hemolytic transfusion reaction caused by anti-Wra in a patient with no other RBC alloantibodies. Serologic investigation showed that one of the RBC units the patient received was Wr(a+). Immunohematology 2021;37:2024.
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Reacción a la Transfusión , Eritrocitos , Femenino , Hemólisis , Humanos , Recién Nacido , Isoanticuerpos , EmbarazoRESUMEN
OBJECTIVE: To examine whether severe mental illnesses (i.e., schizophrenia or bipolar disorder) affected diagnostic testing and treatment for cardiovascular diseases in primary and specialized health care. METHODS: We performed a nationwide study of 72 385 individuals who died from cardiovascular disease, of whom 1487 had been diagnosed with severe mental illnesses. Log-binomial regression analysis was applied to study the impact of severe mental illnesses on the uptake of diagnostic tests (e.g., 24-h blood pressure, glucose/HbA1c measurements, electrocardiography, echocardiography, coronary angiography, and ultrasound of peripheral vessels) and invasive cardiovascular treatments (i.e., revascularization, arrhythmia treatment, and vascular surgery). RESULTS: Patients with and without severe mental illnesses had similar prevalences of cardiovascular diagnostic tests performed in primary care, but patients with schizophrenia had lower prevalences of specialized cardiovascular examinations (prevalence ratio (PR) 0.78; 95% CI 0.73-0.85). Subjects with severe mental illnesses had lower prevalences of invasive cardiovascular treatments (schizophrenia, PR 0.58; 95% CI 0.49-0.70, bipolar disorder, PR 0.78; 95% CI 0.66-0.92). The prevalence of invasive cardiovascular treatments was similar in patients with and without severe mental illnesses when cardiovascular disease was diagnosed before death. CONCLUSION: Better access to specialized cardiovascular examinations is important to ensure equal cardiovascular treatments among individuals with severe mental illnesses.
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Enfermedades Cardiovasculares/mortalidad , Pruebas Diagnósticas de Rutina/estadística & datos numéricos , Trastornos Mentales/epidemiología , Atención Primaria de Salud/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Trastorno Bipolar/epidemiología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/terapia , Causas de Muerte , Femenino , Humanos , Masculino , Persona de Mediana Edad , Noruega/epidemiología , Prevalencia , Factores de Riesgo , Esquizofrenia/epidemiología , Adulto JovenRESUMEN
OBJECTIVE: To examine whether individuals with schizophrenia (SCZ) or bipolar disorder (BD) had equal likelihood of not being diagnosed with cardiovascular disease (CVD) prior to cardiovascular death, compared to individuals without SCZ or BD. METHODS: Multivariate logistic regression analysis including nationwide data of 72 451 cardiovascular deaths in the years 2011-2016. Of these, 814 had a SCZ diagnosis and 673 a BD diagnosis in primary or specialist health care. RESULTS: Individuals with SCZ were 66% more likely (OR: 1.66; 95% CI: 1.39-1.98), women with BD were 38% more likely (adjusted OR: 1.38; 95% CI: 1.04-1.82), and men with BD were equally likely (OR: 0.88, 95% CI: 0.63-1.24) not to be diagnosed with CVD prior to cardiovascular death, compared to individuals without SMI. Almost all (98%) individuals with SMI and undiagnosed CVD had visited primary or specialized somatic health care prior to death, compared to 88% among the other individuals who died of CVD. CONCLUSION: Individuals with SCZ and women with BD are more likely to die due to undiagnosed CVD, despite increased risk of CVD and many contacts with primary and specialized somatic care. Strengthened efforts to prevent, recognize, and treat CVD in individuals with SMI from young age are needed.
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Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/mortalidad , Esquizofrenia/diagnóstico , Esquizofrenia/mortalidad , Índice de Severidad de la Enfermedad , Adulto , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/mortalidad , Enfermedades Cardiovasculares/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo , Esquizofrenia/epidemiología , Adulto JovenRESUMEN
Tributyltin (TBT) is an organotin environmental pollutant widely used as an agricultural and wood biocide and in antifouling paints. Countries began restricting TBT use in the 2000s, but their use continues in some agroindustrial processes. We studied the acute effect of TBT on cardiac function by analyzing myocardial contractility and Ca2+ handling. Cardiac contractility was evaluated in isolated papillary muscle and whole heart upon TBT exposure. Isolated ventricular myocytes were used to measure calcium (Ca2+) transients, sarcoplasmic reticulum (SR) Ca2+ content and SR Ca2+ leak (as Ca2+ sparks). Reactive oxygen species (ROS), as superoxide anion (O2â¢-) was detected at intracellular and mitochondrial myocardium. TBT depressed cardiac contractility and relaxation in papillary muscle and intact whole heart. TBT increased cytosolic, mitochondrial ROS production and decreased mitochondrial membrane potential. In isolated cardiomyocytes TBT decreased both Ca2+ transients and SR Ca2+ content and increased diastolic SR Ca2+ leak. Decay of twitch and caffeine-induced Ca2+ transients were slowed by the presence of TBT. Dantrolene prevented and Tiron limited the reduction in SR Ca2+ content and transients. The environmental contaminant TBT causes cardiotoxicity within minutes, and may be considered hazardous to the mammalian heart. TBT acutely induced a negative inotropic effect in isolated papillary muscle and whole heart, increased arrhythmogenic SR Ca2+ leak leading to reduced SR Ca2+ content and reduced Ca2+ transients. TBT-induced myocardial ROS production, may destabilize the SR Ca2+ release channel RyR2 and reduce SR Ca2+ pump activity as key factors in the TBT-induced negative inotropic and lusitropic effects.
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Cardiotoxicidad/metabolismo , Compuestos de Trialquiltina/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Calcio/metabolismo , Mitocondrias/metabolismo , Contracción Miocárdica , Miocardio/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Estrés Oxidativo/fisiología , Especies Reactivas de Oxígeno/metabolismo , Canal Liberador de Calcio Receptor de Rianodina , Retículo Sarcoplasmático/metabolismoRESUMEN
BACKGROUND AND PURPOSE: Previous studies have shown associations between atrial fibrillation (AF) and cognitive decline. We investigated this association in a prospective population study, focusing on whether stroke risk factors modulated this association in stroke-free women and men. METHODS: We included 4983 participants (57% women) from the fifth survey of the Tromsø Study (Tromsø 5, 2001), of whom 2491 also participated in the sixth survey (Tromsø 6, 2007-2008). Information about age, education, blood pressure, body mass index, lipids, smoking, coffee consumption, physical activity, depression, coronary and valvular heart disease, heart failure and diabetes was obtained at baseline. AF status was based on hospital records. The outcome was change in cognitive score from Tromsø 5 to Tromsø 6, measured by the verbal memory test, the digit-symbol coding test and the tapping test. RESULTS: Mean age at baseline was 65.4 years. The mean reduction in the tapping test scores was significantly larger in participants with AF (5.3 taps/10 s; 95% CI: 3.9, 6.7) compared with those without AF (3.8 taps/10 s; 95% CI: 3.5, 4.1). These estimates were unchanged when adjusted for other risk factors and were similar for both sexes. AF was not associated with change in the digit-symbol coding or the verbal memory tests. CONCLUSION: Atrial fibrillation in stroke-free participants was independently associated with cognitive decline as measured with the tapping test.
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Fibrilación Atrial/complicaciones , Disfunción Cognitiva/complicaciones , Memoria/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/psicología , Disfunción Cognitiva/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Estudios Prospectivos , Desempeño Psicomotor/fisiología , Factores de RiesgoRESUMEN
Five different glomerular immunohistochemistry markers were evaluated and compared in four different acute and chronic rat kidney disease models. Progression of glomerular or podocyte damage was shown in the puromycin aminonucleoside nephrosis (PAN) and Zucker fatty/spontaneously hypertensive heart failure F1 hybrid (ZSF1) rat model. Progression and prevention of glomerular damage was demonstrated in the Zucker diabetic fatty (ZDF) and Dahl salt-sensitive (Dahl SS) rat. Immunohistochemistry was performed for desmin, vimentin, podocin, synaptopodin and Wilms tumor protein-1 (WT-1), and evaluation of glomerular immunohistochemistry markers was done by semiautomated quantitative image analysis. We found desmin and WT-1 as the most sensitive markers for podocyte damage in both acute and chronic glomerular damage followed by vimentin, podocin and synaptopodin. We were able to demonstrate that early podocyte damage as shown by increased desmin and vimentin staining together with either a phenotypic podocyte change or podocyte loss (reduced numbers of WT-1-stained podocytes) drives the progression of glomerular damage. This is followed by a reduction in podocyte-specific proteins such as podocin and synaptopodin. Our report describes the different sensitivity of glomerular or podocyte markers and gives future guidance for the selection of the most sensitive markers for efficacy testing of new drugs as well as for the selection of tissue-based toxicity markers for glomerular or podocyte injury. In addition to functional clinical chemistry markers, desmin and WT-1 immunohistochemistry offers reliable and valuable data on the morphologic state of podocytes.
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Desmina/análisis , Modelos Animales de Enfermedad , Péptidos y Proteínas de Señalización Intracelular/análisis , Enfermedades Renales/metabolismo , Proteínas de la Membrana/análisis , Proteínas de Microfilamentos/análisis , Vimentina/análisis , Proteínas WT1/análisis , Enfermedad Aguda , Animales , Biomarcadores/análisis , Enfermedad Crónica , Inmunohistoquímica , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Progesterone (P4) has emerged as an important hormone-regulating mammary stem cell (MaSC) populations. In breast cancer, P4 and synthetic analogs increase the number of stem-like cells within luminal estrogen receptor (ER)- and progesterone receptor (PR)-positive breast cancers. These cells gain expression of de-differentiated cell markers CD44 and cytokeratin 5 (CK5), lose luminal markers ER and PR, and are more therapy resistant. We previously described that P4 downregulation of microRNA (miR)-29a contributes to the expansion of CD44(high) and CK5(+) cells. Here we investigated P4 downregulation of miR-141, a member of the miR-200 family of tumor suppressors, in facilitating an increase in stem-like breast cancer cells. miR-141 was the sole member of the miR-200 family P4-downregulated at the mature miRNA level in luminal breast cancer cell lines. Stable inhibition of miR-141 alone increased the CD44(high) population, and potentiated P4-mediated increases in both CD44(high) and CK5(+) cells. Loss of miR-141 enhanced both mammosphere formation and tumor initiation. miR-141 directly targeted both PR and signal transducer and activator of transcription 5A (Stat5a), transcription factors important for MaSC expansion. miR-141 depletion increased PR protein levels, even in cell lines where PR expression is estrogen dependent. Stat5a suppression via small interfering RNA or a small-molecule inhibitor reduced the P4-dependent increase in CK5(+) and CD44(high) cells. These data support a mechanism by which P4-triggered loss of miR-141 facilitates breast cancer cell de-differentiation through deregulation of PR and Stat5a, two transcription factors important for controlling mammary cell fate.
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Neoplasias de la Mama/genética , MicroARNs/genética , Células Madre Neoplásicas/efectos de los fármacos , Progesterona/farmacología , Progestinas/farmacología , Factor de Transcripción STAT5/genética , Proteínas Supresoras de Tumor/genética , Animales , Neoplasias de la Mama/patología , Línea Celular Tumoral , Regulación hacia Abajo/efectos de los fármacos , Femenino , Humanos , Receptores de Hialuranos/metabolismo , Queratina-5/metabolismo , Ratones , Trasplante de Neoplasias , Células Madre Neoplásicas/patología , Receptores de ProgesteronaRESUMEN
Existing crop monitoring programs determine the incidence and distribution of plant diseases and pathogens and assess the damage caused within a crop production region. These programs have traditionally used observed or predicted disease and pathogen data and environmental information to prescribe management practices that minimize crop loss. Monitoring programs are especially important for crops with broad geographic distribution or for diseases that can cause rapid and great economic losses. Successful monitoring programs have been developed for several plant diseases, including downy mildew of cucurbits, Fusarium head blight of wheat, potato late blight, and rusts of cereal crops. A recent example of a successful disease-monitoring program for an economically important crop is the soybean rust (SBR) monitoring effort within North America. SBR, caused by the fungus Phakopsora pachyrhizi, was first identified in the continental United States in November 2004. SBR causes moderate to severe yield losses globally. The fungus produces foliar lesions on soybean (Glycine max) and other legume hosts. P. pachyrhizi diverts nutrients from the host to its own growth and reproduction. The lesions also reduce photosynthetic area. Uredinia rupture the host epidermis and diminish stomatal regulation of transpiration to cause tissue desiccation and premature defoliation. Severe soybean yield losses can occur if plants defoliate during the mid-reproductive growth stages. The rapid response to the threat of SBR in North America resulted in an unprecedented amount of information dissemination and the development of a real-time, publicly available monitoring and prediction system known as the Soybean Rust-Pest Information Platform for Extension and Education (SBR-PIPE). The objectives of this article are (i) to highlight the successful response effort to SBR in North America, and (ii) to introduce researchers to the quantity and type of data generated by SBR-PIPE. Data from this system may now be used to answer questions about the biology, ecology, and epidemiology of an important pathogen and disease of soybean.
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This paper investigates the aeration tank settling (ATS) operation in combination with real time control (RTC) as a tool for increasing the hydraulic capacity and improving the treatment efficiency of a wastewater treatment plant (WWTP) during wet weather flows. Results from 7 years' full-scale operational data at the Avedøre WWTP, Denmark, show that ATS operation in combination with RTC increases the hydraulic capacity of the treatment plant with up to 150 and 67% of the design capacity during winter and summer respectively. Compared to the conventional wet weather operation, the ATS in combination with RTC operation resulted in lower effluent concentrations for total phosphate (40-50%), suspended solids (30-60%) and chemical oxygen demand (30-50%), whereas no significant effect was observed on total nitrogen. Apart from the reduced effluent concentrations, the RTC resulted in economic savings in the form of reduced costs for electricity and green taxes. However, in very few cases the ATS operation in combination with RTC was not able to handle design capacity, and some overflows occurred at flows below the design capacity. The frequency of these overflows may increase in the future due to increased rain intensity resulting in shorter prediction time available for ATS.
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Aire , Lluvia , Purificación del Agua/normas , Tiempo (Meteorología)RESUMEN
The female hormone progesterone (P4) promotes the expansion of stem-like cancer cells in estrogen receptor (ER)- and progesterone receptor (PR)-positive breast tumors. The expanded tumor cells lose expression of ER and PR, express the tumor-initiating marker CD44, the progenitor marker cytokeratin 5 (CK5) and are more resistant to standard endocrine and chemotherapies. The mechanisms underlying this hormone-stimulated reprogramming have remained largely unknown. In the present study, we investigated the role of microRNAs in progestin-mediated expansion of this dedifferentiated tumor cell population. We demonstrate that P4 rapidly downregulates miR-29 family members, particularly in the CD44(+) cell population. Downregulation of miR-29 members potentiates the expansion of CK5(+) and CD44(+) cells in response to progestins, and results in increased stem-like properties in vitro and in vivo. We demonstrate that miR-29 directly targets Krüppel-like factor 4 (KLF4), a transcription factor required for the reprogramming of differentiated cells to pluripotent stem cells, and for the maintenance of breast cancer stem cells. These results reveal a novel mechanism, whereby progestins increase the stem cell-like population in hormone-responsive breast cancers, by decreasing miR-29 to augment PR-mediated upregulation of KLF4. Elucidating the mechanisms whereby hormones mediate the expansion of stem-like cells furthers our understanding of the progression of hormone-responsive breast cancers.
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Neoplasias de la Mama/genética , Diferenciación Celular/genética , Factores de Transcripción de Tipo Kruppel/genética , MicroARNs/genética , Progestinas/farmacología , Regiones no Traducidas 3' , Animales , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Receptores de Hialuranos/metabolismo , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel/metabolismo , Ratones , Ratones SCID , MicroARNs/metabolismo , Progesterona/farmacología , Regulación hacia Arriba , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVES: This research aims to study how carotid atherosclerosis is related to growth of infrarenal aortic diameter and aneurysmal formation. DESIGN: Population-based follow-up study. MATERIALS AND METHODS: At baseline, ultrasound examination of the carotid artery and the abdominal aorta was performed in 4241 persons from a general population with no evidence of abdominal aortic aneurysm (AAA). The burden of atherosclerosis was assessed as carotid total plaque area (TPA). After a mean follow-up of 6.3 years, a new ultrasound examination was performed and measurements of the aortic diameter and carotid TPA were repeated. The effects on aortic diameter progression, follow-up diameter and risk for AAA were assessed in multiple linear and logistic regression models according to carotid TPA, adjusted for known risk factors. RESULTS: When analysing AAA as a dichotomous variable, a borderline association between atherosclerosis and AAA could be demonstrated. When modelling aortic diameter as a continuous variable, a 1-SD increase in 5 years' carotid plaque area (ΔTPA) was associated with a 0.12-mm growth in infrarenal aortic diameter (standard error (SE) 0.04) and a 0.20-mm wider aorta at follow-up (SE 0.06). No independent relation was seen for baseline atherosclerosis. CONCLUSIONS: Carotid plaque progression was positively related to growth in infrarenal aortic diameter and aortic diameter at follow-up. Whether this co-variation between plaque growth and aortic diameter growth is causally related or independent events is still an open question.
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Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/diagnóstico , Enfermedades de las Arterias Carótidas/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/epidemiología , Aneurisma de la Aorta Abdominal/patología , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/epidemiología , Dilatación Patológica , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Modelos Lineales , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Noruega/epidemiología , Pronóstico , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , UltrasonografíaRESUMEN
Necropsy examination of an 8-year-old female swamp wallaby (Wallabia bicolor) from a zoological garden revealed four intestinal diverticular outpouchings at the mesenteric border of the jejunum, which were partly ruptured causing a fatal peritonitis. Microscopically, affected small intestinal segments were characterized by an abrupt gap in the muscular layer with subsequent herniation of respective mucosal and submucosal layers, interpreted as acquired pseudodiverticula. Multifocal perforations of these diverticula were associated with prominent fibrinosuppurative serositis with leakage of ingesta. In addition, there was intestinal nematodal endoparasitism with accompanying neutrophilic to eosinophilic enteritis. Small intestinal pseudodiverticula resembling human colonic diverticulosis are rare in animals and can lead to fatal peritonitis by faecal impaction, subsequent transmural inflammation and eventual perforation.
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Animales de Zoológico , Divertículo/veterinaria , Enfermedades Intestinales/veterinaria , Yeyuno/patología , Macropodidae , Peritonitis/veterinaria , Animales , Divertículo/complicaciones , Divertículo/patología , Resultado Fatal , Femenino , Enfermedades Intestinales/patología , Peritonitis/etiología , Peritonitis/patologíaRESUMEN
In a female Thuringian forest goat osteoporosis, dwarfism and anaemia were found. The animal was kept on a hobby farm with 30 further goats that did not show clinical signs. Radiological examination, computed tomographic imaging and pathological examination revealed reduced bone density and numerous fractures associated with limited or completely absent callus formation. Incineration of selected bones did not show any differences concerning the contents of calcium and phosphorus when compared to two control goats. Therefore, a regular mineralisation of the bone matrix was indicated. The dysfunction associated with the osteogenesis was assumed to be a copper deficiency.
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Enfermedades Óseas Metabólicas/veterinaria , Cobre/deficiencia , Enfermedades de las Cabras/etiología , Anemia/etiología , Anemia/veterinaria , Animales , Enfermedades Óseas Metabólicas/diagnóstico por imagen , Enfermedades Óseas Metabólicas/etiología , Enfermedades Óseas Metabólicas/patología , Calcio/análisis , Enanismo/veterinaria , Femenino , Fémur/química , Fémur/patología , Enfermedades de las Cabras/diagnóstico por imagen , Enfermedades de las Cabras/patología , Cabras , Húmero/química , Húmero/patología , Osteoporosis/diagnóstico , Osteoporosis/etiología , Osteoporosis/veterinaria , Fósforo/análisis , Radiografía , Tibia/química , Tibia/patologíaAsunto(s)
Enfermedades de los Caballos/diagnóstico , Hidrocefalia/veterinaria , Imagen por Resonancia Magnética/veterinaria , Animales , Animales Recién Nacidos , Autopsia/veterinaria , Encéfalo/patología , Diagnóstico Diferencial , Femenino , Enfermedades de los Caballos/diagnóstico por imagen , Caballos , Hidrocefalia/diagnóstico , Hidrocefalia/diagnóstico por imagen , Hipoxia-Isquemia Encefálica/diagnóstico , Hipoxia-Isquemia Encefálica/veterinaria , Examen Neurológico/veterinaria , Cráneo/diagnóstico por imagen , Cráneo/patología , Tomografía Computarizada por Rayos X/veterinariaRESUMEN
In the last two decades, the urokinase-type plasminogen activator receptor (uPAR) has been implicated in a number of human pathologies such as cancer, bacterial infections, and paroxysmal nocturnal hemoglobinuria. The primary function of this glycolipid-anchored receptor is to focalize uPA-mediated plasminogen activation at the cell surface, which is accomplished by its high-affinity interaction with the growth factor-like domain of uPA. Detailed insights into the molecular basis underlying the interactions between uPAR and its two bona fide ligands, uPA and vitronectin, have been obtained recently by X-ray crystallography and surface plasmon resonance studies. Importantly, these structural studies also define possible druggable target sites in uPAR for small molecules and provide guidelines for the development of reporter groups applicable for non-invasive molecular imaging of uPAR expression in vivo by positron emission tomography. In this review, we will discuss recent advances in our perception of the structure-function relationships of uPAR ligation and how these may assist translational research in preclinical intervention studies of uPAR function.
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Sondas Moleculares , Terapia Molecular Dirigida , Receptores del Activador de Plasminógeno Tipo Uroquinasa/antagonistas & inhibidores , Animales , Silenciador del Gen , Humanos , Imagen Multimodal/métodos , Tomografía de Emisión de Positrones/métodos , Conformación Proteica , Receptores del Activador de Plasminógeno Tipo Uroquinasa/química , Receptores del Activador de Plasminógeno Tipo Uroquinasa/genética , Receptores del Activador de Plasminógeno Tipo Uroquinasa/metabolismo , Transducción de Señal/efectos de los fármacos , Especificidad de la Especie , Tomografía Computarizada por Rayos X , Investigación Biomédica Traslacional , Activador de Plasminógeno de Tipo Uroquinasa/antagonistas & inhibidores , Activador de Plasminógeno de Tipo Uroquinasa/química , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo , Vitronectina/química , Vitronectina/metabolismoRESUMEN
Pneumonic lesions occurring in calves after respiratory infection with Mycoplasma bovis are characterized by subacute or chronic suppurative bronchopneumonia with multiple foci of necrosis and by persistence of M. bovis antigen, which is frequently associated with phagocytes at the periphery of the necrotic foci. The aims of this study were: (1) to investigate the expression of inducible nitric oxide synthase (iNOS), nitrotyrosine (NT) and manganese superoxide dismutase (Mn-SOD) in the lung lesions of calves infected experimentally with M. bovis, and (2) to analyse the distribution and localization of M. bovis DNA by in-situ hybridization and correlate these findings with the immunohistochemical detection of M. bovis antigen. Phagocytic cells infiltrating the lung tissue were characterized using the markers CD68, S100A8 and S100A9. Lung tissue from 18 infected calves and three non-infected controls were examined. All infected calves had an increased number of cells expressing iNOS, NT and Mn-SOD in the inflamed lung tissue. These molecules were most strongly expressed by macrophages demarcating necrotic areas, by altered bronchiolar epithelial cells and by macrophages within obliterated bronchioles. Co-localization of M. bovis DNA, M. bovis antigen and macrophages expressing iNOS, NT and Mn-SOD was observed. These findings suggest that the generation of reactive oxygen and nitrogen species is involved in the development of severe chronic lung damage in M. bovis infection.
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Enfermedades de los Bovinos/microbiología , Infecciones por Mycoplasma/veterinaria , Mycoplasma bovis/aislamiento & purificación , Óxido Nítrico Sintasa de Tipo II/biosíntesis , Neumonía/veterinaria , Superóxido Dismutasa/biosíntesis , Tirosina/análogos & derivados , Animales , Bovinos , Enfermedades de los Bovinos/inmunología , Enfermedades de los Bovinos/metabolismo , ADN Bacteriano/análisis , ADN Bacteriano/aislamiento & purificación , Inmunohistoquímica , Hibridación in Situ , Pulmón/inmunología , Pulmón/metabolismo , Pulmón/microbiología , Infecciones por Mycoplasma/inmunología , Infecciones por Mycoplasma/metabolismo , Mycoplasma bovis/genética , Neumonía/inmunología , Neumonía/metabolismo , Neumonía/microbiología , Tirosina/biosíntesisRESUMEN
UNLABELLED: In this open population-based study from Northern Norway, there was no increase in hip fracture incidence in women and men from 1994 to 2008. Age-adjusted hip fracture rates was lower compared to reported rates from the Norwegian capital Oslo, indicating regional differences within the country. INTRODUCTION: The aim of the present population-based study was to describe age- and sex-specific incidence of hip fractures in a Northern Norwegian city, compare rates with the Norwegian capital Oslo, describe time trends in hip fracture incidence, place of injury, seasonal variation and compare mortality after hip fracture between women and men. METHODS: Data on hip fractures from 1994 to 2008 in women and men aged 50 years and above were obtained from the Harstad Injury Registry. RESULTS: There were altogether 603 hip fractures in Harstad between 1994 and 2008. The annual incidenc rose exponentially from 5.8 to 349.2 per 10,000 in men, and from 8.7 to 582.2 per 10,000 in women from the age group 50-54 to 90+ years. The age-adjusted incidence rates were 101.0 and 37.4 in women and men, respectively, compared to 118.0 in women (p = 0.005) and 44.0 in men (p = 0.09) in Oslo. The age-adjusted incidence rates did not increase between 1994-1996 and 2006-2008. The majority of hip fractures occurred indoors and seasonal variation was significant in fractures occurring outdoors only. After adjusting for age at hip fracture, mortality after fracture was higher in men than in women 3, 6 and 12 months (p ≤ 0.002) after fracture. CONCLUSIONS: There are regional differences in hip fracture incidence that cannot be explained by a north-south gradient in Norway. Preventive strategies must be targeted to indoor areas throughout the year and to outdoor areas in winter.
Asunto(s)
Fracturas de Cadera/epidemiología , Distribución por Edad , Anciano , Anciano de 80 o más Años , Femenino , Fracturas de Cadera/mortalidad , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Noruega/epidemiología , Sistema de Registros , Factores de Riesgo , Estaciones del Año , Distribución por SexoRESUMEN
UNLABELLED: Few studies have examined the association between body mass index (BMI) change and fracture in a general population. We observed that BMI loss was associated with increased fracture risk in non-smoking men and women, but not in smokers. BMI gain was associated with decreased fracture risk in women. INTRODUCTION: Weight loss has been associated with increased fracture risk, but few studies have included men. The aim of this study was to examine the association between BMI change and fracture risk in both genders. METHODS: A population-based cohort study in Tromsø, Norway, of adults, aged 20 to 54 years in 1979, who participated in two or three health surveys in 1979-1980, 1986-1987, and 1994-1995. Weight and height were measured at each survey. Information about lifestyle was obtained by questionnaires. Poisson regression was used to estimate incidence rates and Cox proportional hazards regression model to assess the association between fracture risk and BMI change. Fractional polynomials were used to accommodate non-linear associations. RESULTS: A total of 5,549 men and 5,428 women participated. There were 1,135 fractures during 10 years of follow-up. Reduction in BMI was associated with increased non-vertebral fracture risk in non-smokers, but not in smokers. The hazard ratio in male and female non-smokers per 10-year BMI decrease of 2 kg/m(2) versus a BMI increase of 1 kg/m(2) was 1.79 (95% confidence interval (CI), 1.17-2.75) and 1.60 (95% CI, 1.28-1.99), respectively. The association was not significantly modified by initial BMI or age or by exclusion of subjects with cardiovascular diseases, diabetes, or cancer. In female non-smokers, weight gain was inversely associated with fracture risk. CONCLUSIONS: In a general Norwegian population, reduction in BMI was significantly associated with increased fracture risk in male and female non-smokers, but not in smokers. These findings could not be explained by preexisting disease.
Asunto(s)
Índice de Masa Corporal , Fracturas Óseas/etiología , Adulto , Antropometría/métodos , Métodos Epidemiológicos , Femenino , Fracturas Óseas/epidemiología , Fracturas Óseas/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Actividad Motora/fisiología , Noruega/epidemiología , Factores Sexuales , Fumar/epidemiología , Pérdida de Peso/fisiología , Adulto JovenRESUMEN
UNLABELLED: In this longitudinal study of 4,160 postmenopausal women (3,947 without and 213 with self-reported diabetes), smoking was strongly related to fracture risk in those with diabetes. INTRODUCTION: Smoking is related to low bone mass and increased risk of fracture risk in postmenopausal women of the general population. The aim of the present longitudinal population-based study was to examine the effect of smoking on the risk of non-vertebral fractures in women ≥ 55 years of age, with specific focus on its relationship with diabetes. METHODS: A total of 4,160 women (3,947 without and 213 with self-reported diabetes) from the municipality of Tromsø, Norway, were followed for a mean of 7.6 years. Measurements of height and weight and questionnaire information concerning smoking and alcohol consumption habits, physical activity, prevalent diseases, and use of medication were collected before the start of follow-up. Non-vertebral fractures were registered during follow-up. RESULTS: A total of 1,015 without and 66 with diabetes sustained a new non-vertebral fracture. Smoking status (never, past, and current) was significantly associated with an increased risk of fracture both in women with and without diabetes (p values for trend 0.02 and <0.001, respectively, after adjustments for age), but in women without diabetes, the relationship was no longer significant after multiple adjustments. There was a strong interaction between smoking status and diabetes on fracture risk (p= 0.004). Women with diabetes who were current smokers had a 3.47 (95% CI 1.82-6.62) higher risk of non-vertebral fractures than diabetic women who were never smokers (p value for linear trend = 0.001, after multiple adjustments). CONCLUSION: We conclude that smoking is strongly related to fracture risk in postmenopausal women with self-reported diabetes.