Does improved functional performance help to reduce urinary incontinence in institutionalized older women? a multicenter randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Urinary incontinence (UI) is a major problem in older women. Management is usually restricted to dealing with the consequences instead of treating underlying causes such as bladder dysfunction or reduced mobility.</p> <p>The aim of this multicenter randomized controlled trial was to compare a group-based behavioral exercise program to prevent or reduce UI, with usual care. The exercise program aimed to improve functional performance of pelvic floor muscle (PFM), bladder and physical performance of women living in homes for the elderly.</p> <p>Methods</p> <p>Twenty participating Dutch homes were matched and randomized into intervention or control homes using a random number generator. Homes recruited 6–10 older women, with or without UI, with sufficient cognitive and physical function to participate in the program comprising behavioral aspects of continence and physical exercises to improve PFM, bladder and physical performance. The program consisted of a weekly group training session and homework exercises and ran for 6 months during which time the control group participants received care as usual. Primary outcome measures after 6 months were presence or absence of UI, frequency of episodes (measured by participants and caregivers (not blinded) using a 3-day bladder diary) and the Physical Performance Test (blinded). Linear and logistic regression analysis based on the Intention to Treat (ITT) principle using an imputed data set and per protocol analysis including all participants who completed the study and intervention (minimal attendance of 14 sessions).</p> <p>Results</p> <p>102 participants were allocated to the program and 90 to care as usual. ITT analysis (n = 85 intervention, n = 70 control) showed improvement of physical performance (intervention +8%; control −7%) and no differences on other primary and secondary outcome measures. Per protocol analysis (n = 51 intervention, n = 60 control) showed a reduction of participants with UI (intervention −40%; control −28%) and in frequency of episodes (intervention −51%; control −42%) in both groups; improvement of physical performance (intervention + 13%; control −4%) was related to participation in the exercise program.</p> <p>Conclusions</p> <p>This study shows that improving physical performance is feasible in institutionalized older women by exercise. Observed reductions in UI were not related to the intervention. [Current Controlled Trials ISRCTN63368283]</p

NK Cell–Like Behavior of Vα14i NK T Cells during MCMV Infection

Immunity to the murine cytomegalovirus (MCMV) is critically dependent on the innate response for initial containment of viral replication, resolution of active infection, and proper induction of the adaptive phase of the anti-viral response. In contrast to NK cells, the Vα14 invariant natural killer T cell response to MCMV has not been examined. We found that Vα14i NK T cells become activated and produce significant levels of IFN-γ, but do not proliferate or produce IL-4 following MCMV infection. In vivo treatment with an anti-CD1d mAb and adoptive transfer of Vα14i NK T cells into MCMV-infected CD1d−/− mice demonstrate that CD1d is dispensable for Vα14i NK T cell activation. In contrast, both IFN-α/β and IL-12 are required for optimal activation. Vα14i NK T cell–derived IFN-γ is partially dependent on IFN-α/β but highly dependent on IL-12. Vα14i NK T cells contribute to the immune response to MCMV and amplify NK cell–derived IFN-γ. Importantly, mortality is increased in CD1d−/− mice in response to high dose MCMV infection when compared to heterozygote littermate controls. Collectively, these findings illustrate the plasticity of Vα14i NK T cells that act as effector T cells during bacterial infection, but have NK cell–like behavior during the innate immune response to MCMV infection

Archaeology, Architecture, and the Postcolonial Critique

Peer reviewe

Nothing Lasts Forever: Environmental Discourses on the Collapse of Past Societies

The study of the collapse of past societies raises many questions for the theory and practice of archaeology. Interest in collapse extends as well into the natural sciences and environmental and sustainability policy. Despite a range of approaches to collapse, the predominant paradigm is environmental collapse, which I argue obscures recognition of the dynamic role of social processes that lie at the heart of human communities. These environmental discourses, together with confusion over terminology and the concepts of collapse, have created widespread aporia about collapse and resulted in the creation of mixed messages about complex historical and social processes

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

Statistiek bij het gebruik van microbiologische (gecertificeerde) referentiematerialen

Als microbiologische laboratoria de kwaliteit van hun metingen en analyses willen beheersen en verbeteren kan dat gedaan worden door (gecertificeerde) referentiematerialen, (C)RM's, te kopen en in te zetten. Om efficient incidenteel gebruik van CRM's en routinematig gebruik van (niet gecertificeerde) RM's te bewerkstelligen worden in dit rapport de behandeling en beperkingen van (C)RM's toegelicht vanuit statistisch oogpunt. Statistische methodieken worden gebruikt om het benodigde aantal microbiologische analyses in een experiment te bepalen. Voor de gebruiker zijn betrouwbaarheidsgrenzen van de gecertificeerde waarde beschikbaar. Als de laboratoriumwaarde van een gebruiker gelijk is aan de gecertificeerde waarde, is het wenselijk om een hoge kans te hebben om dat ook te concluderen. Als de laboratoriumwaarde van een gebruiker meer dan een vooraf bepaalde hoeveelheid afwijkt van de gecertificeerde waarde is het wenselijk om dat op te sporen. Afhankelijk van het kleinste vooraf bepaalde verschil dat opgespoord zou moeten worden, kunnen per bacteriestam en per methode berekeningen uitgevoerd worden om te bepalen wat het optimale aantal capsules en replica's is om te gebruiken. Voor hoogbesmette CRM's lopen de afwijkingen die aangetoond kunnen worden voor de verschillende CRM's uiteen. Die afwijking hangt namelijk af van de variantie van het materiaal en de methode zoals die gevonden is in de certificeringsstudie. Het heeft geen zin om meer capsules te analyseren dan het aanbevolen aantal van 3-5 capsules (afhankelijk van de stam en de methode) en 2 replica's omdat de additionele winst dan verwaarloosbaar is. Voor laagbesmette CRM's moet een enorm aantal capsules geanalyseerd worden om kleine verschillen tussen een fractie negatieven van een laboratorium en de gecertificeerde fractie negatieven te kunnen opsporen. Maar in tegenstelling tot de situatie bij hoogbesmette CRM's heeft het nu wel zin om meer capsules te analyseren dan de 5 capsules daar. Er is namelijk een additionele winst te behalen in de zin van de mogelijkheid om (kleinere) verschillen te kunnen opsporen. Het aantal in te zetten capsules is weer afhankelijk van het kleinste verschil tussen gecertificeerde fractie negatieven en een fractie negatieven van een laboratorium dat microbiologisch gezien opgespoord zou moeten kunnen worden. Er is een aanzienlijke kloof tussen wat wenselijk is vanuit microbiologisch oogpunt en wat in de praktijk haalbaar is. Daarom wordt voor laagbesmette CRM's aangeraden om het maximale aantal capsules dat nog handelbaar is in een keer in te zetten. Regelkaarten (of controlekaarten) kunnen zeer nuttig zijn bij de dagelijkse kwaliteitscontrole met hoogbesmette (niet gecertificeerde) RM's. Met de regelkaarten die hier gebruikt zijn wordt de gemiddelde waarde van een proces voortdurend kritisch gevolgd. De kaarten dienen met zorg gebruikt en geinterpreteerd te worden. Voor routinematig gebruik van laagbesmette (niet gecertificeerde) RM's wordt geadviseerd een capsule per keer in te zetten en negatieve resultaten niet zonder meer te accepteren. Het analyse- en meetproces moet elke keer dat een capsule een negatief resultaat oplevert gecontroleerd worden.Microbiological laboratories may wish to control and improve the quality of their measurements and analytical results. This can be done by purchasing and examining (Certified) Reference Materials. In order to facilitate efficient incidental use of CRMs and routine use of (non-certified) RMs, in this report the treatment and limitations of (data from) (C)RMs are described from a statistical background. Statistical methods are used to determine the required number of microbiological analyses in an experiment. Confidence limits of the certified value for users are available. If a user's laboratory value is similar to the certified value it is desirable to conclude with a high probability that both values are equivalent. If the user's laboratory value differs from the certified value by more than a predetermined amount it is desirable to detect this. Dependent on the smallest predetermined difference that should be detected, per material and per method then computations can be performed to determine the best number of capsules and replicates to use. For high level CRMs the difference that can be detected varies between different CRMs. This difference depends on the variance for the material and method as found in the collaborative certification study. The additional benefit of analysing more capsules and replicates than the recommended number of about 3-5 capsules (depending on material and method) and 2 replicates is negligible. For low level CRMs a very large number of capsules has to be analysed to detect small differences between a laboratory fraction of negatives and the certified value. But, in contrast with high level CRMs here it makes sense to analyse more capsules than 5, because then there is additional benefit in the ability to detect (smaller) differences. Again the number of capsules depends on the smallest difference between the certified fraction of negatives and a laboratory fraction of negatives that should be detectable from a microbiological point of view. There is a considerable discrepancy between what is microbiologically desirable and what is realizable in practice. Therefore for low level CRMs it is recommended to analyse as many capsules as can be handled in one time. Control charts may be very helpful for day-to-day quality control for high level (non-certified) RMs. With the control charts demonstrated here the average result of the process is under scrutiny. The charts should be used and interpreted with care. For routine use of low level (non-certified) RMs, the advise is to analyse one capsule at a time and not to accept a negative result without making investigations. The process of analysis and measurement should be checked every time a negative result for a capsule occurs.RIV

[Telling van Escherichia coli in referentie materialen voor de levensmiddelenmicrobiologie. BCR/FOOD trial 6.]

Abstract niet beschikbaarA collaborative study was organised to test the reference material (RM) for Escherichia coli. Twenty eight laboratories participated in this international collaborative study, each laboratory testing 8 capsules. Each set of eight capsules contained one uncontaminated sample. The RM was enumerated by four methods, two for E.coli and two for Enterobacteriaceae. For both E.coli and Enterobacteriaceae one of two methods was standardized for all laboratories (called standard method or SM), the other method was chosen by the participating laboratory (called OWN method). The highest counts were obtained using the E.coli standard method. Sixteen of the 25 laboratories found higher counts using the SM than with their OWN method. The group of laboratories using a resuscitation step for the E.coli-OWN method found significantly more colonies than the group which did not. The average counts obtained for the Enterobacteriaceae methods were very low, too low for optimal use of the RM tested. This indicates that the methods for the enumeration of Enterobacteriaseae using VRBG agar have a low recovery. The values found for repeatability (r) and reproducibility (R) were high compared to the B.sereus and S.aureus RM's tested in the previous trial. The stability of the material, determined using the E.coli standard method, indicated that the material is not yet stable. The reference material is therefore as yeat not suitable for commencing the certification procedure.EUMeasurement and Testing Programme (BCR