The Effect of Age on the Underlying Abilities of Mindfulness Practice

INTRODUCTION: Cognitive control and acceptance are considered as two key underlying processes of mindfulness practice. Recent evidence has shown that increasing age is related to a decline in cognitive control and the enhancement of emotional regulation and, consequently, acceptance. However, the effect of age on both underlying processes has not been investigated within a sample of older adults and younger adults using clinically relevant measures. AIMS: To determine whether there is a difference in performance between an older adult group and a younger adult group on measures of the cognitive control/awareness and emotion regulation/acceptance elements of mindfulness. It hypothesised that older adult would perform worse that younger adults on measures of cognitive control and better on measure of emotion regulation/ acceptance. DESIGN: Cross-sectional between-groups design with one older adult group and one younger adult group. Measures were administrated in a face-to-face research interview. A total of 55 older healthy adults aged 65+ (M=72.5) and 55 younger healthy adults aged 18-25 (M= 21.30) were recruited from the community for participation. RESULTS: The results revealed that older adults performed better in mindfulness measures of cognitive control/awareness whereas younger adults performed better in mindfulness measures of emotion regulation/acceptance. CONCLUSION: Age might compromise the underlying processes of mindfulness practice. The results were discussed in light of available literature and with reference to limitations and clinical implications

Plasma interleukin-6 concentration for the diagnosis of sepsis in critically ill adults

© 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Background The definition of sepsis has evolved over time, along with the clinical and scientific knowledge behind it. For years, sepsis was defined as a systemic inflammatory response syndrome (SIRS) in the presence of a documented or suspected infection. At present, sepsis is defined as a life-threatening organ dysfunction resulting from a dysregulated host response to infection. Even though sepsis is one of the leading causes of mortality in critically ill patients, and the World Health Organization (WHO) recognizes it as a healthcare priority, it still lacks an accurate diagnostic test. Determining the accuracy of interleukin-6 (IL-6) concentrations in plasma, which is proposed as a new biomarker for the diagnosis of sepsis, might be helpful to provide adequate and timely management of critically ill patients, and thus reduce the morbidity and mortality associated with this condition. Objectives To determine the diagnostic accuracy of plasma interleukin-6 (IL-6) concentration for the diagnosis of bacterial sepsis in critically ill adults. Search methods We searched CENTRAL, MEDLINE, Embase, LILACS, and Web of Science on 25 January 2019. We screened references in the included studies to identify additional studies. We did not apply any language restriction to the electronic searches. Selection criteria We included diagnostic accuracy studies enrolling critically ill adults aged 18 years or older under suspicion of sepsis during their hospitalization, where IL-6 concentrations were evaluated by serological measurement. Data collection and analysis Two review authors independently screened the references to identify relevant studies and extracted data. We assessed the methodological quality of studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We estimated a summary receiver operating characteristic (SROC) curve by fitting a hierarchical summary ROC (HSROC) non-linear mixed model. We explored sources of heterogeneity using the HSROC model parameters. We conducted all analyses in the SAS statistical software package and R software. Main results We included 23 studies (n = 4192) assessing the accuracy of IL-6 for the diagnosis of sepsis in critically ill adults. Twenty studies that were available as conference proceedings only are awaiting classification. The included participants were heterogeneous in terms of their distribution of age, gender, main diagnosis, setting, country, positivity threshold, sepsis criteria, year of publication, and origin of infection, among other factors. Prevalence of sepsis greatly varied across studies, ranging from 12% to 78%. We considered all studies to be at high risk of bias due to issues related to the index test domain in QUADAS-2. The SROC curve showed a great dispersion in individual studies accuracy estimates (21 studies, 3650 adult patients), therefore the considerable heterogeneity in the collected data prevented us from calculating formal accuracy estimates. Using a fixed prevalence of sepsis of 50% and a fixed specificity of 74%, we found a sensitivity of 66% (95% confidence interval 60 to 72). If we test a cohort 1000 adult patients under suspicion of sepsis with IL-6, we will find that 330 patients would receive appropriate and timely antibiotic therapy, while 130 patients would be wrongly considered to have sepsis. In addition, 370 out of 1000 patients would avoid unnecessary antibiotic therapy, and 170 patients would have been undiagnosed of sepsis. This numerical approach should be interpreted with caution due to the limitations described above. Authors’ conclusions Our evidence assessment of plasma interleukin-6 concentrations for the diagnosis of sepsis in critically ill adults reveals several limitations. High heterogeneity of collected evidence regarding the main diagnosis, setting, country, positivity threshold, sepsis criteria, year of publication, and the origin of infection, among other factors, along with the potential number of misclassifications, remain significant constraints for its implementation. The 20 conference proceedings assessed as studies awaiting classification may alter the conclusions of the review once they are fully published and evaluated. Further studies about the accuracy of interleukin-6 for the diagnosis of sepsis in adults that apply rigorous methodology for conducting diagnostic test accuracy studies are needed. The conclusions of the review will likely change once the 20 studies pending publication are fully published and included

Development of a fuzzy logic-based solar charge controller for charging lead-acid batteries

Este documento se considera que es una ponencia de congresos en lugar de un artículo.International Conference on Computer Science, Electronics and Industrial Engineering (CSEI 2019), Oct. 28-31 2019, Ambato (Ecuador)The design and implementation of a solar charge controller for lead-acid batteries is intended to supplement a component of the water purification module of the water treatment unit for natural disaster relief. This unit contains a solar panel system that supplies power to the module by charging batteries through a controller comprising an Atmega 328 processor. The solar panel feeds voltage to the batteries through fuzzy logic-based software, which allows up to 6 A DC to pass through the controller's power circuit. Consequently, the battery was charged in less time (an average of 7 h to reach maximum capacity), wherein battery lifespan is related to the charge wave frequency. Thus, our software may be adapted in different control algorithms without having to change hardware

Chitosan encapsulation modulates the effect of capsaicin on the tight junctions of MDCK cells

Capsaicin has known pharmacological effects including the ability to reversibly open cellular tight junctions, among others. The aim of this study was to develop a strategy to enhance the paracellular transport of a substance with low permeability (FITC-dextran) across an epithelial cell monolayer via reversible opening of cellular tight junctions using a nanosystem comprised by capsaicin and of chitosan. We compared the biophysical properties of free capsaicin and capsaicin-loaded chitosan nanocapsules, including their cytotoxicity towards epithelial MDCK-C7 cells and their effect on the integrity of tight junctions, membrane permeability and cellular uptake. The cytotoxic response of MDCK-C7 cells to capsaicin at a concentration of 500 μM, which was evident for the free compound, is not observable following its encapsulation. The interaction between nanocapsules and the tight junctions of MDCK-C7 cells was investigated by impedance spectroscopy, digital holographic microscopy and structured illumination fluorescence microscopy. The nanocapsules modulated the interaction between capsaicin and tight junctions as shown by the different time profile of trans-epithelial electrical resistance and the enhanced permeability of monolayers incubated with FITC-dextran. Structured illumination fluorescence microscopy showed that the nanocapsules were internalized by MDCK-C7 cells. The capsaicin-loaded nanocapsules could be further developed as drug nanocarriers with enhanced epithelial permeability

Efficacy of haloperidol to decrease the burden of delirium in adult critically ill patients:the EuRIDICE randomized clinical trial

Background:The role of haloperidol as treatment for ICU delirium and related symptoms remains controversial despite two recent large controlled trials evaluating its efficacy and safety. We sought to determine whether haloperidol when compared to placebo in critically ill adults with delirium reduces days with delirium and coma and improves delirium-related sequelae.Methods:This multi-center double-blind, placebo-controlled randomized trial at eight mixed medical-surgical Dutch ICUs included critically ill adults with delirium (Intensive Care Delirium Screening Checklist ≥ 4 or a positive Confusion Assessment Method for the ICU) admitted between February 2018 and January 2020. Patients were randomized to intravenous haloperidol 2.5 mg or placebo every 8 h, titrated up to 5 mg every 8 h if delirium persisted until ICU discharge or up to 14 days. The primary outcome was ICU delirium- and coma-free days (DCFDs) within 14 days after randomization. Predefined secondary outcomes included the protocolized use of sedatives for agitation and related behaviors, patient-initiated extubation and invasive device removal, adverse drug associated events, mechanical ventilation, ICU length of stay, 28-day mortality, and long-term outcomes up to 1-year after randomization.Results:The trial was terminated prematurely for primary endpoint futility on DSMB advice after enrolment of 132 (65 haloperidol; 67 placebo) patients [mean age 64 (15) years, APACHE IV score 73.1 (33.9), male 68%]. Haloperidol did not increase DCFDs (adjusted RR 0.98 [95% CI 0.73–1.31], p = 0.87). Patients treated with haloperidol (vs. placebo) were less likely to receive benzodiazepines (adjusted OR 0.41 [95% CI 0.18–0.89], p = 0.02). Effect measures of other secondary outcomes related to agitation (use of open label haloperidol [OR 0.43 (95% CI 0.12–1.56)] and other antipsychotics [OR 0.63 (95% CI 0.29–1.32)], self-extubation or invasive device removal [OR 0.70 (95% CI 0.22–2.18)]) appeared consistently more favorable with haloperidol, but the confidence interval also included harm. Adverse drug events were not different. Long-term secondary outcomes (e.g., ICU recall and quality of life) warrant further study.Conclusions:Haloperidol does not reduce delirium in critically ill delirious adults. However, it may reduce rescue medication requirements and agitation-related events in delirious ICU patients warranting further evaluation.Trial registration: ClinicalTrials.gov (#NCT03628391), October 9, 2017

Risk assessment of adding Gasodor S-Free to natural gas

Om te herkennen wanneer te veel aardgas vrijkomt, en zo explosies te voorkomen, wordt er een geurstof aan toegevoegd. De huidige geurstof (tetrahydrothiofeen) bevat zwavel. Om de uitstoot van zwavel naar het milieu verder te verminderen onderzoekt Gasunie Transport Services de mogelijkheid om een andere, zwavelvrije geurstof, toe te voegen: Gasodor S-Free. Vanwege het omvangrijke gebruik van aardgas is het van belang voldoende zicht te hebben op mogelijke risico's van dit product. Het RIVM heeft onvoldoende informatie kunnen vinden om vast te stellen of het gebruik van Gasodor S-Free als geurstof in aardgas veilig is. De zorg bestaat dat dit product allergische reacties kan veroorzaken als het wordt ingeademd. Het gebruik van Gasodor S-Free wordt afgeraden totdat meer duidelijk is over het mogelijke risico op allergische reacties. Het RIVM geeft aanbevelingen voor vervolgonderzoek om het risico op deze reacties beter te kunnen beoordelen. Gasodor S-Free is een mengsel van drie stoffen, voornamelijk ethylacrylaat en methylacrylaat (samen 95 procent of meer), en een kleine fractie 2-ethyl-3-methylpyrazine. Mogelijke gevolgen van de twee hoofdbestanddelen zijn op basis van de huidige kennis niet goed te beoordelen. Bekend is dat ethylacrylaat en methylacrylaat de luchtwegen kunnen irriteren, maar door de lage concentraties worden geen normen overschreden. Ook zijn ze niet kankerverwekkend. Het is bekend dat beide stoffen allergische reacties kunnen veroorzaken bij huidcontact. Vergelijkbare effecten zouden ook kunnen optreden als de stof wordt ingeademd, maar dit kan op basis van de beschikbare informatie niet worden beoordeeld. Over nadelige effecten van de derde stof (2-ethyl-3-methylpyrazine) is onvoldoende informatie beschikbaar om een uitspraak te kunnen doen over mogelijke effecten op mens en milieu.As natural gas is odourless, an odorant is added to detect the release of gas and prevent explosions. The odorant (tetrahydrothiophene) that is currently used contains sulphur. So as not to add to current levels of sulphur in the environment, Gasunie Transport Services has investigated the possibility of adding another sulphur-free fragrance: Gasodor S-Free. Because of the extensive use of natural gas, it is important that the potential risks of this product are thoroughly evaluated. RIVM has not been able to find sufficient information to determine whether the use of Gasodor S-Free as an odorant in natural gas is safe. There is a concern that this product can cause allergic reactions if inhaled. Any application of Gasodor S-Free, therefore, should be discouraged until the possible risk of allergic reactions has been clarified. RIVM provides recommendations about which investigations could be conducted to assess the risk of these reactions more comprehensively. Gasodor S-Free is a mixture of three substances, mainly ethyl acrylate and methyl acrylate (together 95 percent or more), and a small percent of 2-ethyl-3-methylpyrazine. The possible consequences of the two main components cannot be judged properly based on current knowledge. Ethyl acrylate and methyl acrylate are known to irritate the respiratory tract, but the low concentrations in intended use of Gasodor S-Free do not exceed standards. Nor are they carcinogenic. However, it is known that both substances can cause allergic contact dermatitis. Allergic effects could also occur if the substance is inhaled, but this cannot be evaluated based on the available information. There is also insufficient information available on the adverse effects of the third substance (2-ethyl-3-methylpyrazine) for an assessment of the possible effects on humans and the environment to be madeSod

Polycomb-mediated silencing in neuroendocrine prostate cancer

BACKGROUND: Neuroendocrine prostate cancer (NEPC) is a highly aggressive subtype of prostate cancer (PCa) for which the median survival remains less than a year. Current treatments are only palliative in nature, and the lack of suitable pre-clinical models has hampered previous efforts to develop novel therapeutic strategies. Addressing this need, we have recently established the first in vivo model of complete neuroendocrine transdifferentiation using patient-derived xenografts. Few genetic differences were observed between parental PCa and relapsed NEPC, suggesting that NEPC likely results from alterations that are epigenetic in nature. Thus, we sought to identify targetable epigenetic regulators whose expression was elevated in NEPC using genome-wide profiling of patient-derived xenografts and clinical samples. RESULTS: Our data indicate that multiple members of the polycomb group (PcG) family of transcriptional repressors were selectively upregulated in NEPC. Notably, CBX2 and EZH2 were consistently the most highly overexpressed epigenetic regulators across multiple datasets from clinical and xenograft tumor tissues. Given the striking upregulation of PcG genes and other transcriptional repressors, we derived a 185-gene list termed 'neuroendocrine-associated repression signature' (NEARS) by overlapping transcripts downregulated across multiple in vivo NEPC models. In line with the striking upregulation of PcG family members, NEARS was preferentially enriched with PcG target genes, suggesting a driving role for PcG silencing in NEPC. Importantly, NEARS was significantly associated with high-grade tumors, metastatic progression, and poor outcome in multiple clinical datasets, consistent with extensive literature linking PcG genes and aggressive disease progression. CONCLUSIONS: We have explored the epigenetic landscape of NEPC and provided evidence of increased PcG-mediated silencing associated with aberrant transcriptional regulation of key differentiation genes. Our results position CBX2 and EZH2 as potential therapeutic targets in NEPC, providing opportunities to explore novel strategies aimed at reversing epigenetic alterations driving this lethal disease

A New Minimal-Stress Freely-Moving Rat Model for Preclinical Studies on Intranasal Administration of CNS Drugs

Purpose. To develop a new minimal-stress model for intranasal administration in freely moving rats and to evaluate in this model the brain distribution of acetaminophen following intranasal versus intravenous administration. Methods. Male Wistar rats received one intranasal cannula, an intra-cerebral microdialysis probe, and two blood cannulas for drug administration and serial blood sampling respectively. To evaluate this novel model, the following experiments were conducted. 1) Evans Blue was administered to verify the selectivity of intranasal exposure. 2) During a 1 min infusion 10, 20, or 40 μl saline was administered intranasally or 250 µl intravenously. Corticosterone plasma concentrations over time were compared as biomarkers for stress. 3) 200 µg of the model drug acetaminophen was given in identical setup and plasma, and brain pharmacokinetics were determined. Results. In 96 % of the rats, only the targeted nasal cavity was deeply colored. Corticosterone plasma concentrations were not influenced, neither by route nor volume of administration. Pharmacokinetics of acetaminophen were identical after intravenous and intranasal administration, although the Cmax in microdialysates was reached a little earlier following intravenous administration. Conclusion. A new minimal-stress model for intranasal administration in freely moving rats has been successfully developed and allows direct comparison with intravenous administration. KEY WORDS: acetaminophen; brain; intranasal infusion; microdialysis; pharmacokinetics

Nanoencapsulated capsaicin changes migration behavior and morphology of madin darby canine kidney cell monolayers

We have developed a drug delivery nanosystem based on chitosan and capsaicin. Both substances have a wide range of biological activities. We investigated the nanosystem’s influence on migration and morphology of Madin Darby canine kidney (MDCK-C7) epithelial cells in comparison to the capsaicin-free nanoformulation, free capsaicin, and control cells. For minimally-invasive quantification of cell migration, we applied label-free digital holographic microscopy (DHM) and single-cell tracking. Moreover, quantitative DHM phase images were used as novel stain-free assay to quantify the temporal course of global cellular morphology changes in confluent cell layers. Cytoskeleton alterations and tight junction protein redistributions were complementary analyzed by fluorescence microscopy. Calcium influx measurements were conducted to characterize the influence of the nanoformulations and capsaicin on ion channel activities. We found that both, capsaicin-loaded and unloaded chitosan nanocapsules, and also free capsaicin, have a significant impact on directed cell migration and cellular motility. Increase of velocity and directionality of cell migration correlates with changes in the cell layer surface roughness, tight junction integrity and cytoskeleton alterations. Calcium influx into cells occurred only after nanoformulation treatment but not upon addition of free capsaicin. Our results pave the way for further studies on the biological significance of these findings and potential biomedical applications, e.g. as drug and gene carriers

Short-term stability in refractive status despite large fluctuations in glucose levels in diabetes mellitus type 1 and 2

Purpose: This work investigates how short-term changes in blood glucose concentration affect the refractive components of the diabetic eye in patients with long-term Type 1 and Type 2 diabetes. Methods: Blood glucose concentration, refractive error components (mean spherical equivalent MSE, J0, J45), central corneal thickness (CCT), anterior chamber depth (ACD), crystalline lens thickness (LT), axial length (AL) and ocular aberrations were monitored at two-hourly intervals over a 12-hour period in: 20 T1DM patients (mean age ± SD) 38±14 years, baseline HbA1c 8.6±1.9%; 21 T2DM patients (mean age ± SD) 56±11 years, HbA1c 7.5±1.8%; and in 20 control subjects (mean age ± SD) 49±23 years, HbA1c 5.5±0.5%. The refractive and biometric results were compared with the corresponding changes in blood glucose concentration. Results: Blood glucose concentration at different times was found to vary significantly within (p0.05). Minor changes of marginal statistical or optical significance were observed in some biometric parameters. Similarly there were some marginally significant differences between the baseline biometric parameters of well-controlled and poorly-controlled diabetic subjects. Conclusion: This work suggests that normal, short-term fluctuations (of up to about 6 mM/l on a timescale of a few hours) in the blood glucose levels of diabetics are not usually associated with acute changes in refractive error or ocular wavefront aberrations. It is therefore possible that factors other than refractive error fluctuations are sometimes responsible for the transient visual problems often reported by diabetic patients