Exosomes and Exosomal miRNA in Respiratory Diseases

Exosomes are nanosized vesicles released from every cell in the body including those in the respiratory tract and lungs. They are found in most body fluids and contain a number of different biomolecules including proteins, lipids, and both mRNA and noncoding RNAs. Since they can release their contents, particularly miRNAs, to both neighboring and distal cells, they are considered important in cell-cell communication. Recent evidence has shown their possible importance in the pathogenesis of several pulmonary diseases. The differential expression of exosomes and of exosomal miRNAs in disease has driven their promise as biomarkers of disease enabling noninvasive clinical diagnosis in addition to their use as therapeutic tools. In this review, we summarize recent advances in this area as applicable to pulmonary diseases

Zelfdoding onder migrantengroepen en autochtonen

Doel. De verschillen vaststellen in incidentie van zelfdoding tussen autochtonen en allochtonen, gerubriceerd naar regio en land van herkomst, rekening houdend met verschillen in leeftijdsopbouw. Opzet. Retrospectief. Methode. Gegevens van de statistiek van de doodsoorzaken van het Centraal Bureau voor de Statistiek (CBS), gebaseerd op de doodsoorzaakverklaringen door arts of lijkschouwer, werden gekoppeld aan het bericht van overlijden uit de gemeentelijke basisadministratie (GBA). Zo kon de herkomst van de overledene worden bepaald op basis van gegevens uit de GBA. De geheimhouding van deze gegevens is wettelijk vastgelegd. Over de jaren 1996-2004 werden alle 13.737 personen geselecteerd die waren overleden door zelfdoding (‘International classification of diseases’(ICD)-10-codes X60-X84). De herkomst werd bepaald aan de hand van gegevens over het geboorteland van de overleden persoon en diens ouders. Iemand is ‘allochtoon’ volgens de definitie van het CBS als ten minste één van de ouders in het buitenland is geboren. Resultaten. Er waren aanzienlijke verschillen in sterfte door zelfdoding tussen migrantengroepen in Nederland. Deze verschillen weerspiegelden deels de suïcidecijfers in de landen en regio’s van herkomst. Migranten uit westerse landen lieten in het algemeen hogere suïcidecijfers zien dan autochtonen. Hoge suïcidecijfers werden waargenomen onder Zuid- en Oost-Europese mannelijke migranten. De suïcidecijfers voor Turken en Marokkanen waren daarentegen significant lager dan die voor autochtonen. Alleen op jongvolwassen leeftijd liepen niet-westerse allochtone mannen, uitgezonderd Marokkanen, een beduidend hoger risico om door zelfdoding te overlijden. Conclusie. Hoewel er veel aandacht is voor pogingen tot suïcide onder Surinaamse vrouwen, waren hun suïcidecijfers minder sterk verhoogd dan die van Surinaamse mannen tot middelbare leeftijd. Mogelijk weerspiegelen deze hoge suïcidecijfers een verhoogd niveau van psychiatrische ziekten, identiteitsproblemen, teleurstellingen in het migratieproces, verwachtingen ten aanzien van opleiding, werk en inkomen, en de verantwoordelijkheid voor gezin en familie

Reduced Phagocytic Capacity of Blood Monocyte/Macrophages in Tuberculosis Patients Is Further Reduced by Smoking.

Tuberculosis (TB) and tobacco use are two major alarming global health issues posing immense threats to human populations. Mycobacterium tuberculosis (MTB) by activation of macrophages could induce the sequences of cells activation and releases of inflammatory cytokines such as CXCL-8, Il-12 and TNF-α which in turn induces the immune system network. However no information is available on other activity of cells by MTB and smoking. In the current study we aimed to investigate the serum levels TNF-a, CXCL-8 and phagocytosis capacity in tuberculosis patients with and without smoking. 103 subjects entered the study including 61 new diagnosed pulmonary TB patients (23 smokers and 38 nonsmokers) and 42 control healthy subjects. The phagocytosis of fluorescein isothiocyanate dextran (FITC-dextran) in blood monocytes/macrophages through flowcytometry was assessed. Serum levels of TNF-a and CXCL-8 were analyzed by ELISA methods. A lower percentage of cells from TB patients who smoked [50.29% (43.4-57.2), p<0.01] took up FITC-dextran after 2h compared to non-smoking TB subjects [71.62% (69.2-74.1)] and healthy cases [97.45% (95.9-99.1). Phagocytic capacity was inversely correlated with cigarette smoking as measured by pack years (r=-0.73, p<0.001). The serum levels of TNF-a and CXCL-8 were significantly higher in the TB patients who smoked compared to the TB non-smoker group (p<0.001, p<0.01 respectively). Blood monocytes/macrophages from TB patients have reduced phagocytic capacity which is further reduced in TB patients who smoke. Smoking enhanced serum levels of TNF-a and CXCL-8 suggesting a greater imbalance between the proinflammatory and anti-inflammatory factors in these patients

Cellijnen en Salmonella

In human gastrointestinal disease caused by Salmonella, transepithelial migration of neutrophils follows the attachment of bacteria to epithelial tissue. This migration of neutrophils is stimulated by the release of chemokines, including interleukin-8 (Il -8), from the epithelial cells. We have developed an in vitro model system (human epithelial monolayers, among which Caco-2 cells grown on microtiter multiwell plates) for studying host-pathogen interactions. After infection with different pathogens we measured Il-8 production during time. Results showed that Il-8 release was time related and varied with the pathogen. Salmonella enteritidis (Se) did induce the highest response. Subsequently, three doses of this Se strain were used and the Il-8 response was measured at different time points. Caco-2 cells remained intact over a period of 24h, the production of Il-8 increased in time and was found to be Se dose-dependent. Other tested epithelial monolayers, such as HT29 colon cancer cells, gave similar results.Infectie met Salmonella kan gepaard gaan met de invasie van darmepitheelcellen. De aan de invasie voorafgaande aanhechting leidt reeds tot de transmigratie van witte bloedcellen (neutrofielen) vanuit de bloedbaan naar het epitheelweefsel. De migratie wordt gestimuleerd door de productie van chemokines, waaronder interleukine-8 (Il-8) door epitheelcellen. Wij hebben een in vitro model systeem ontwikkeld (humaan epitheelweefsel gekweekt in microtiterplaten) waarin gastheer - pathogeen interacties kunnen worden bestudeerd. Epitheelcellen zijn gedurende een uur blootgesteld aan verschillende pathogene micro-organismen, waarna de Il-8 response is gemeten. Als controle zijn meegenomen een Escherichia coli stam zonder LPS en een probiotische Lactobacillus. De resultaten laten zien dat de IL-8 productie per pathogeen varieert, waarbij Salmonella enteritidis de hoogste respons geeft. In vervolgexperimenten zijn drie concentraties S. enteritidis gebruikt, waarna de respons gedurende 24 uur is gemeten. De gebruikte cellijn bleek na 24 uur nog intact, de Il-8 productie correleerde met de doses, en nam toe in de tijd. Hieruit kan geconcludeerd worden dat het door ons ontwikkelde model gebruikt kan worden voor het bestuderen van factoren die van invloed zijn op dosis-respons relaties. De respons betreft dan prikkeling van het immuunsysteem ten gevolge van adhesie en invasie van darmepitheelcellen door salmonellae. Tenslotte wordt een benaderingwijze voorgesteld om resultaten van in vitro dosis-respons experimenten te vertalen naar de mens

What Immunological Defects Predispose to Non-tuberculosis Mycobacterial Infections?

Nontuberculous mycobacteria (NTM) are categorized as one of the large and diverse groups of environmental organisms which are abundant in water and soil.  NTM cause a variety of diseases in humans that mainly affect the lung. A predisposition to pulmonary NTM is evident in patients with parenchymal structural diseases including bronchiectasis, emphysema, tuberculosis (TB), cystic fibrosis (CF), rheumatologic lung diseases and other chronic diseases with pulmonary manifestations. Lung infections are not the only consequences of being infected by NTM as they can also infect skin and soft tissue and may also cause lymphadenitis (predominantly in young children) and disseminated disease in human immunodeficiency virus (HIV)-infected patients or those with severely compromised immune system. NTM are also found in many subjects without any known risk factors.  Although the recent advances in imaging and microbiologic techniques including gene sequencing have provided a better view of the problems caused by NTM and has enhanced our understanding of the disease, many uncertainties regarding the immunologic response to NTM still exist. There is also limited data on the immunogenetics of NTM infection. Here, the authors reviewed the main immunogenetic defects as well as other immunological conditions which are associated with an increased the risk of NTM infections

Quantum Universe on Extremely Small Space-time Scales

The semiclassical approach to the quantum geometrodynamical model is used for the description of the properties of the Universe on extremely small space-time scales. Under this approach, the matter in the Universe has two components of the quantum nature which behave as antigravitating fluids. The first component does not vanish in the limit ħ → 0 and can be associated with dark energy. The second component is described by an extremely rigid equation of state and goes to zero after the transition to large space-time scales. On small space-time scales, this quantum correction turns out to be significant. It determines the geometry of the Universe near the initial cosmological singularity point. This geometry is conformal to a unit four-sphere embedded in a five-dimensional Euclidean flat space. During the consequent expansion of the Universe, when reaching the post-Planck era, the geometry of the Universe changes into that conformal to a unit four-hyperboloid in a five-dimensional Lorentz-signatured flat space. This agrees with the hypothesis about the possible change of geometry after the origin of the expanding Universe from the region near the initial singularity point. The origin of the Universe can be interpreted as a quantum transition of the system from a region in the phase space forbidden for the classical motion, but where a trajectory in imaginary time exists, into a region, where the equations of motion have the solution which describes the evolution of the Universe in real time. Near the boundary between two regions, from the side of real time, the Universe undergoes almost an exponential expansion which passes smoothly into the expansion under the action of radiation dominating over matter which is described by the standard cosmological model.Квазiкласичний пiдхiд до квантово-геометродинамiчної моделi застосовано для опису властивостей всесвiту на екстремально малих просторово-часових масштабах. У цьому пiдходi матерiя у всесвiтi має двi компоненти квантової природи, якi поводять себе як антигравiтуючi рiдини. Перша компонента не набуває нульового значення в границi ħ → 0 та може бути асоцiйована з темною енергiєю. Друга компонента описується екстремально жорстким рiвнянням стану i прямує до нуля пiсля переходу до великих просторово-часових масштабiв. На малих просторовочасових масштабах ця квантова поправка вiдiграє значну роль. Вона визначає геометрiю всесвiту бiля точки початкової космологiчної сингулярностi. Ця геометрiя є конформною до одиничної 4-сфери, зануреної у 5-вимiрний евклiдовий плоский простiр. Пiд час наступного розширення всесвiту, пiсля досягнення пост-планкiвської ери, геометрiя всесвiту перетворюється на геометрiю, конформну до одиничного 4-гiперболоїда у 5- вимiрному плоскому просторi з лоренцiвською сигнатурою. Це узгоджується з гiпотезою про можливу змiну геометрiї пiсля виникнення всесвiту, що розширюється з областi поблизу точки початкової сингулярностi. Виникнення всесвiту може бути iнтерпретовано як квантовий перехiд системи з областi у фазовому просторi, забороненої для класичного руху, але де iснує траєкторiя в уявному часi, в область, де рiвняння руху мають розв’язок, що описує еволюцiю всесвiту у реальному часi. Поблизу межi мiж двома областями, з боку реального часу, всесвiт зазнає майже експоненцiального розширення, яке гладко переходить у розширення пiд дiєю випромiнювання, що домiнує над матерiєю, у вiдповiдностi iз стандартною космологiчною моделлю

Структура кредитной политики коммерческого банка

В статье раскрывается структура кредитной политики коммерческого банка

Принятие решений в условиях многокритериальности с комбинаторными свойствами альтернатив

В статье рассматривается задача принятия решений при многих критериях на комбинаторных конфигурациях. Такие задачи являются моделями многих практических задач. Обосновываются свойства области допустимых решений задачи, базирующиеся на свойствах многогранника размещений, вершины которого определяют заданное комбинаторное множество точек. Представлено множество альтернатив в виде ориентированного графа многогранника размещений. Описываются свойства графа многогранника размещений, которые используются для разработки нового метода решений предлагаемой задачи на графе.У статті розглядується задача прийняття рішень при багатьох критеріях на комбінаторних конфігураціях. Такі задачі є моделями багатьох практичних задач. Обґрунтовуються властивості області допустимих рішень задачі, що базуються на властивостях многогранника розміщень, вершини якого визначають задану комбінаторну множину точок. Представлено множину альтернатив у вигляді орієнтованого графа многогранника розміщень. Описуються властивості графа многогранника розміщень, які використовуються для розробки нового методу розв’язання пропонованої задачі на графі.In article the decision-making task is considered at many criteria on combinatorial configurations which is models of many practical tasks. Properties of area of admissible solutions the tasks which are based on properties of a polyhedron of allocations which tops define the set combinatorial point set are proved. It is presented sets of alternatives in the form of a graph of a polyhedron of allocations. Properties of a polyhedron graph of allocations which are used for development of a new method of solutions of the offered task on the graph are described

The Role of the Spiritual Meaning System in Coping with Cancer

Spirituality can support the adjustment process of people with cancer, by forming a meaning system that supports understanding of the cause and implications of the experience and that provides coping strategies. The different ways in which spiritual meaning systems might fulfill these roles were examined among 20 people who were treated for cancer with curative intent. Narrative interviews were held on average 16 months after cancer diagnosis. The interviews were analyzed in a two-stage process, based on a holistic content approach. The first stage led to the identification of various roles and outcomes of the meaning system. The second stage involved a comparison of these roles and outcomes between previously defined types of meaning systems. The roles identified were discrepancy, legitimation and continuation. Legitimation was associated with the outcome of integration, whereas continuation was associated with an outcome of a positive outlook toward the future. Several differences were found between types of meaning systems, regarding the extent to which and ways in which these roles and outcomes occurred. This study underscores recommendations that healthcare professionals should be aware of the different ways in which the patient’s previous beliefs and experiences influence their current adaptation to serious life events