A prospective study of asthma incidence and its predictors: the RHINE study.

To access publisher full text version of this article. Please click on the hyperlink in Additional LinkThe objective of this longitudinal study was to estimate the incidence rate of asthma, and to compare the incidence between subjects with or without baseline reporting of certain respiratory symptoms. A follow-up of the random population samples in the European Respiratory Health Survey (ECRHS) in Sweden, Norway, Denmark, Iceland and Estonia was conducted in 1999-2001, in a population aged 30-54 yrs at follow-up (n=14,731). Asthma was defined as reporting either asthma or physician-diagnosed asthma, and a reported year when asthma symptoms were first noticed. Incidence rates, incidence rate ratios and hazard ratios were calculated with 95% confidence intervals. The incidence rate of asthma was 2.2 cases per 1,000 person-yrs. The incidence was higher among females (2.9 cases.1,000 person-yrs(-1)) than among males (1.5 cases.1,000 person-yrs(-1)). When subjects with baseline reporting of wheezing were excluded, the incidence rate decreased to 1.7 cases.1,000 person-yrs(-1), with a further decrease to 1.5 cases.1,000 person-yrs(-1) after exclusion of subjects with wheezing, nocturnal dyspnoea, chest tightness and cough. There was a strong association between onset of asthma and wheezing at baseline. In this prospective, population-based study, the incidence rate of asthma in the whole population sample ranged 1.5-2.2.1,000 person-yrs(-1), with a higher incidence range among females. The incidence was dependent on the extent to which subjects with respiratory symptoms were excluded from follow-up. Hence, for comparability between studies, the exclusion criteria in the follow-up population must be stated

Neutralisation of uPA with a Monoclonal Antibody Reduces Plasmin Formation and Delays Skin Wound Healing in tPA-Deficient Mice

Background: Proteolytic degradation by plasmin and metalloproteinases is essential for epidermal regeneration in skin wound healing. Plasminogen deficient mice have severely delayed wound closure as have mice simultaneously lacking the two plasminogen activators, urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA). In contrast, individual genetic deficiencies in either uPA or tPA lead to wound healing kinetics with no or only slightly delayed closure of skin wounds. Methodology/Principal Findings: To evaluate the therapeutic potential in vivo of a murine neutralizing antibody directed against mouse uPA we investigated the efficacy in skin wound healing of tPA-deficient mice. Systemic administration of the anti-mouse uPA monoclonal antibody, mU1, to tPA-deficient mice caused a dose-dependent delay of skin wound closure almost similar to the delayed kinetics observed in uPA;tPA double-deficient mice. Analysis of wound extracts showed diminished levels of plasmin in the mU1-treated tPA-deficent mice. Immunohistochemistry revealed that fibrin accumulated in the wounds of such mU1-treated tPA-deficent mice and that keratinocyte tongues were aberrant. Together these abnormalities lead to compromised epidermal closure. Conclusions/Significance: Our findings demonstrate that inhibition of uPA activity with a monoclonal antibody in adult tPA-deficient mice mimics the effect of simultaneous genetic ablation of uPA and tPA. Thus, application of the murin

Cancer cell differentiation heterogeneity and aggressive behavior in solid tumors

The differentiation stage of tumors is a central aspect in the histopathological classification of solid malignancies. The differentiation stage is strongly associated with tumor behavior, and generally an immature tumor is more aggressive than the more differentiated counterpart. While this is common knowledge in surgical pathology, the contribution of differentiation-related gene expression and functions to tumor behavior is often overlooked in the experimental, tumor biological setting. The mechanisms by which tumor cell differentiation stages are perturbed or affected are poorly explored but have recently come into focus with the introduction.of the tumor stem cell concept. While developmental biologists view the differentiation as a unidirectional event, pathologists and tumor biologists have introduced the concept of dedifferentiation to explain phenotypic changes occurring in solid tumors. In this review we discuss the impact of the tumor cell differentiation stage as used in surgical pathology. We further discuss knowledge gained from exploring the molecular basis of the differentiation and dedifferentiation processes in neuroblastoma and breast cancer, two tumor forms where the tumor cell differentiation concept is used in the clinical diagnostic work and where the tumor stem cell theory has been applied

Distinct ¹⁸F-AV-1451 tau PET retention patterns in early- and late-onset Alzheimer’s disease

Patients with Alzheimer's disease can present with different clinical phenotypes. Individuals with late-onset Alzheimer's disease (>65 years) typically present with medial temporal lobe neurodegeneration and predominantly amnestic symptomatology, while patients with early-onset Alzheimer's disease (<65 years) exhibit greater neocortical involvement associated with a clinical presentation including dyspraxia, executive dysfunction, or visuospatial impairment. We recruited 20 patients with early-onset Alzheimer's disease, 21 with late-onset Alzheimer's disease, three with prodromal early-onset Alzheimer's disease and 13 with prodromal late-onset Alzheimer's disease, as well as 30 cognitively healthy elderly controls, that had undergone 18F-AV-1451 tau positron emission tomography and structural magnetic resonance imaging to explore whether early- and late-onset Alzheimer's disease exhibit differential regional tau pathology and atrophy patterns. Strong associations of lower age at symptom onset with higher 18F-AV-1451 uptake were observed in several neocortical regions, while higher age did not yield positive associations in neither patient group. Comparing patients with early-onset Alzheimer's disease with controls resulted in significantly higher 18F-AV-1451 retention throughout the neocortex, while comparing healthy controls with late-onset Alzheimer's disease patients yielded a distinct pattern of higher 18F-AV-1451 retention, predominantly confined to temporal lobe regions. When compared against each other, the early-onset Alzheimer's disease group exhibited greater uptake than the late-onset group in prefrontal and premotor, as well as in inferior parietal cortex. These preliminary findings indicate that age may constitute an important contributor to Alzheimer's disease heterogeneity highlighting the potential of tau positron emission tomography to capture phenotypic variation across patients with Alzheimer's disease

Energy landscapes in random systems, driven interfaces and wetting

We discuss the zero-temperature susceptibility of elastic manifolds with quenched randomness. It diverges with system size due to low-lying local minima. The distribution of energy gaps is deduced to be constant in the limit of vanishing gaps by comparing numerics with a probabilistic argument. The typical manifold response arises from a level-crossing phenomenon and implies that wetting in random systems begins with a discrete transition. The associated ``jump field'' scales as $\sim L^{-5/3}$ and $L^{-2.2}$ for (1+1) and (2+1) dimensional manifolds with random bond disorder.Comment: Accepted for publication in Phys. Rev. Let

Dragon-kings: mechanisms, statistical methods and empirical evidence

This introductory article presents the special Discussion and Debate volume "From black swans to dragon-kings, is there life beyond power laws?" published in Eur. Phys. J. Special Topics in May 2012. We summarize and put in perspective the contributions into three main themes: (i) mechanisms for dragon-kings, (ii) detection of dragon-kings and statistical tests and (iii) empirical evidence in a large variety of natural and social systems. Overall, we are pleased to witness significant advances both in the introduction and clarification of underlying mechanisms and in the development of novel efficient tests that demonstrate clear evidence for the presence of dragon-kings in many systems. However, this positive view should be balanced by the fact that this remains a very delicate and difficult field, if only due to the scarcity of data as well as the extraordinary important implications with respect to hazard assessment, risk control and predictability.Comment: 20 page

Allergotoxicology: Research of Pollutant Influence on the Development of Allergic Reactions

Alergotoksikologija je znanstvenoistraživačko područje koje se bavi ispitivanjem utjecaja polutanata (onečišćivača zraka) na nastanak alergijskih reakcija i bolesti. Ispitivanja su prvobitno bila usmjerena na polutante vanjskih prostora, a u novije vrijeme sve više na polutante unutarnjih prostora u kojima ljudi provode većinu vremena. Polutanti po svojoj prirodi mogu biti krute, tekuće ili plinovite čestice, koje se razlikuju s obzirom na veličinu, sastav i izvor iz kojeg nastaju. S obzirom na izvor mogu biti biološkog i nebiološkog podrijetla. Polutanti koji su predmet suvremenih istraživanja s gledišta nastanka alergijskih bolesti su respirabilne krute čestice, ozon, dušični oksidi i bioaerosoli. Mehanizam djelovanja polutanata ovisi o veličini čestica, njihovoj topljivosti i mjestu ulaska u organizam. Dosadašnja ispitivanja su pokazala da različite čestice uvjetuju različite imunosne i neimunosne odgovore u organizmu. Interakcija polutanata i alergena može se zbivati izvan eksponirane osobe, tj. sa samim alergenom ili u eksponiranoj osobi na sluznicama i koži. Polutanti mogu biti nosioci alergena i mogu interferirati na različitim nivoima u nastanku alergijske reakcije. U ovom prikazu razma raju se dosadašnja saznanja o mehanizmima djelovanja polutanata na alergene, na imunosni sustav izloženih osoba na osnovi epidemioloških populacijskih istraživanja, kliničkih studija ekspozcije u kontroliranim uvjetima i eksperimentalnih testnih sistema in vivo i in vitro.Allergotoxicology studies the infl uence of pollutants on the development of allergic reactions and diseases. At the beginning, the research was focused on outdoor air pollutants, while recently it turns to the indoor environment, mainly because people this is where people spend most of their time. Air pollutants may be solid, soluble, or gaseous particles in nature, and they can differ in size, structure, and sources. Pollutants can be of biological or nonbiological origin. Currently interesting air pollutants include particulate matter, ozone, nitrogen oxides, and bioaerosols. The mechanisms of pollutant activity depend on the particle size, solubility, site of deposition, and specifi c chemical properties. Recent studies have shown that different pollutants provoke different immunological and nonimmunological responses in exposed persons. Interaction between air pollutants and allergens can take place outside the exposed person i.e. with allergen itself, or inside the organism on mucous membranes and skin. Pollutants may be the carriers of allergens and may exacerbate allergic reactions and diseases. This review presents recent views about the mechanisms of pollutant activity on allergens and immune system response in exposed persons, based on epidemiological population studies, clinical studies of exposure under controlled conditions, and experimental tests in vitro and in vivo