253 research outputs found
Stimulated by Novelty? The role of Psychological Needs and Perceived Creativity
In the current research we aimed to address the inconsistent finding in the brainstorming literature that cognitive stimulation sometimes results from novel input, yet other times from non-novel input. We expected and found, in three experiments, that the strength and valence of this relationship is moderated by people's psychological needs for structure and autonomy. Specifically, the effect of novel input (vs. non-novel input), through perceived creativity, on cognitive stimulation was stronger for people who were either low in need for structure or high in need for autonomy. Also, when the input people received did not fit their needs, they experienced less psychological cognitive stimulation from this input (i.e., less task enjoyment and feeling more blocked) compared with when they did not receive any input. Hence, to create the ideal circumstances for people to achieve cognitive stimulation when brainstorming, input novelty should be aligned with their psychological needs
Presence of tobramycin in blood and urine during selective decontamination of the digestive tract in critically ill patients, a prospective cohort study
Tobramycin is one of the components used for selective decontamination of the digestive tract (SDD), applied to prevent colonization and subsequent infections in critically ill patients. Tobramycin is administered in the oropharynx and gastrointestinal tract and is normally not absorbed. However, critical illness may convey gut barrier failure. The aim of the study was to assess the prevalence and amount of tobramycin leakage from the gut into the blood, to quantify tobramycin excretion in urine, and to determine the association of tobramycin leakage with markers of circulation, kidney function and other organ failure. This was a prospective observational cohort study. The setting was the 20-bed closed format-mixed ICU of a teaching hospital. The study population was critically ill patients with an expected stay of more than two days, receiving SDD with tobramycin, polymyxin-E and amphotericin-B four times daily in the oropharynx and stomach. Tobramycin concentration was measured in serum (sensitive high performance liquid chromatography - mass spectrometry/mass spectrometry (HLPC-MS/MS) assay) and 24-hour urine (conventional immunoassay), in 34 patients, 24 hours after ICU admission, and in 71 patients, once daily for 7 days. Tobramycin leakage was defined as tobramycin detected in serum at least once (> 0.05 mg/L). Ototoxicity was not monitored. Of the 100 patients with available blood samples, 83 had tobramycin leakage. Median highest serum concentration for each patient was 0.12 mg/L; 99% of the patients had at least one positive urinary sample (> 0.5 mg/L), 49% had a urinary concentration ≥ 1 mg/L. The highest tobramycin serum concentration was significantly associated with vasopressor support, renal and hepatic dysfunction, and C-reactive protein. At binary logistic regression analysis, high dopamine dose and low urinary output on Day 1 were the significant predictors of tobramycin leakage. Nephrotoxicity could not be shown. The majority of acute critically ill patients treated with enteral tobramycin as a component of SDD had traces of tobramycin in the blood, especially those with severe shock, inflammation and subsequent acute kidney injury, suggesting loss of gut barrier and decreased renal removal. Unexpectedly, urinary tobramycin was above the therapeutic trough level in half of the patients. Nephrotoxicity could not be demonstrated
Drug-administration sequence does not change pharmacodynamics and kinetics of irinotecan and cisplatin
In this study, 11 patients with solid tumors were randomized to receive
irinotecan (CPT-11; 200 mg/m2) as a 90-min i.v. infusion, immediately
followed by cisplatin (CDDP; 80 mg/m2) as a 3-h i.v. infusion in the first
course and the reversed sequence in the second course or vice versa. No
significant differences in any toxicity were observed between the
treatment schedules (decrease in absolute neutrophil count, 74.7 +/- 18.3
versus 80.3 +/- 18.0%; P = 0.41). CPT-11 lactone clearance was similar to
single agent data and not significantly different between study courses
(60.4 +/- 17.1 versus 65.5 +/- 16.3 liter/h/m2; P = 0.66). The kinetic
profiles of the major CPT-11 metabolites SN-38, SN-38 glucuronide,
7-ethyl-10-[4-N-(5-aminopentanoic
acid)-1-piperidinolcarbonyloxycamptothecine (APC), and
7-ethyl-10-[4-N-(1-piperidino)-1-amino]carbonyloxycamptothecine (NPC) were
also sequence independent (P > or = 0.20). In addition, CPT-11 had no
influence on the clearance of nonprotein-bound CDDP (40.8 +/- 16.7 versus
50.3 +/- 18.6 liter/h/m2; P = 0.08) and the platinum DNA-adduct formation
in peripheral leukocytes in either sequence (1.94 +/- 2.20 versus 2.42 +/-
1.62 pg Pt/microg DNA; P = 0.41). These data indicate that the toxicity of
the combination CPT-11 and CDDP is schedule independent and that there is
no mutual pharmacokinetic interaction
The comparative evidence basis for the efficacy of second-generation antidepressants in the treatment of depression in the US: A Bayesian meta-analysis of Food and Drug Administration reviews
Background Studies have shown similar efficacy of different antidepressants in the treatment of depression. Method Data of phase-2 and -3 clinical-trials for 16 antidepressants (levomilnacipran, desvenlafaxine, duloxetine, venlafaxine, paroxetine, escitalopram, vortioxetine, mirtazapine, venlafaxine XR, sertraline, fluoxetine, citalopram, paroxetine CR, nefazodone, bupropion, vilazodone), approved by the FDA for the treatment of depression between 1987 and 2016, were extracted from the FDA reviews that were used to evaluate efficacy prior to marketing approval, which are less liable to reporting biases. Meta-analytic Bayes factors, which quantify the strength of evidence for efficacy, were calculated. In addition, posterior pooled effect-sizes were calculated and compared with classical estimations. Results The resulted Bayes factors showed that the evidence load for efficacy varied strongly across antidepressants. However, all tested drugs except for bupropion and vilazodone showed strong evidence for their efficacy. The posterior effect-size distributions showed variation across antidepressants, with the highest pooled estimated effect size for venlafaxine followed by paroxetine, and the lowest for bupropion and vilazodone. Limitations Not all published trials were included in the study. Conclusions The results illustrate the importance of considering both the effect size and the evidence-load when judging the efficacy of a treatment. In doing so, the currently employed Bayesian approach provided clear insights on top of those gained with traditional approaches
#243 Patterns and trends in the clinical practice of corpus uteri cancer in Belgium: an analysis of the effect database
peer reviewe
Lipid-mediated Wnt protein stabilization enables serum-free culture of human organ stem cells
Wnt signalling proteins are essential for culture of human organ stem cells in organoids, but most Wnt protein formulations are poorly active in serum-free media. Here we show that purified Wnt3a protein is ineffective because it rapidly loses activity in culture media due to its hydrophobic nature, and its solubilization requires a detergent, CHAPS (3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate), that interferes with stem cell self-renewal. By stabilizing the Wnt3a protein using phospholipids and cholesterol as carriers, we address both problems: Wnt activity remains stable in serum-free media, while non-toxic carriers allow the use of high Wnt concentrations. Stabilized Wnt3a supports strongly increased self-renewal of organ and embryonic stem cells and the serum-free establishment of human organoids from healthy and diseased intestine and liver. Moreover, the lipophilicity of Wnt3a protein greatly facilitates its purification. Our findings remove a major obstacle impeding clinical applications of adult stem cells and offer advantages for all cell culture uses of Wnt3a protein
Assessing cell-specific effects of genetic variations using tRNA microarrays
Background: By definition, effect of synonymous single-nucleotide variants (SNVs) on protein folding and function are neutral, as they alter the codon and not the encoded amino acid. Recent examples indicate tissue-specific and transfer RNA (tRNA)-dependent effects of some genetic variations arguing against neutrality of synonymous SNVs for protein biogenesis. Results: We performed systematic analysis of tRNA abunandance across in various models used in cystic fibrosis (CF) research and drug development, including Fischer rat thyroid (FRT) cells, patient-derived primary human bronchial epithelia (HBE) from lung biopsies, primary human nasal epithelia (HNE) from nasal curettage, intestinal organoids, and airway progenitor-directed differentiation of human induced pluripotent stem cells (iPSCs). These were compared to an immortalized CF bronchial cell model (CFBE41o-) and two widely used laboratory cell lines, HeLa and HEK293. We discovered that specific synonymous SNVs exhibited differential effects which correlated with variable concentrations of cognate tRNAs. Conclusions: Our results highlight ways in which the presence of synonymous SNVs may alter local kinetics of mRNA translation; and thus, impact protein biogenesis and function. This effect is likely to influence results from mechansistic analysis and/or drug screeining efforts, and establishes importance of cereful model system selection based on genetic variation profile
Emergency Department to ICU Time Is Associated With Hospital Mortality: A Registry Analysis of 14,788 Patients From Six University Hospitals in The Netherlands*
Objectives: Prolonged emergency department to ICU waiting time
may delay intensive care treatment, which could negatively affect patient outcomes. The aim of this study was to investigate whether emergency department to ICU time is associated with hospital mortality.
Design, Setting, and Patients: We conducted a retrospective observational cohort study using data from the Dutch quality registry
National Intensive Care Evaluation. Adult patients admitted to the
ICU directly from the emergency department in six university hospitals, between 2009 and 2016, were included. Using a logistic
regression model, we investigated the crude and adjusted (for disease severity; Acute Physiology and Chronic Health Evaluation
IV probability) odds ratios of emergency department to ICU time
on mortality. In addition, we assessed whether the Acute Physiology and Chronic Health Evaluation IV probability modified the
effect of emergency department to ICU time on mortality. Secondary outcomes were ICU, 30-day, and 90-day mortality.
Interventions: None.
Measurements and Main Results: A total of 14,788 patients were
included. The median emergency department to ICU time was
2.0 hours (interquartile range, 1.3–3.3hr). Emergency department to ICU time was correlated to adjusted hospital mortality
(p < 0.002), in particular in patients with the highest Acute Physiology and Chronic Health Evaluation IV probability and long emergency department to ICU time quintiles: odds ratio, 1.29; 95% CI,
1.02–1.64 (2.4–3.7hr) and odds ratio, 1.54; 95% CI, 1.11–2.14
(> 3.7hr), both compared with the reference category (< 1.2hr).
For 30-day and 90-day mortality, we found similar results. However, emergency department to ICU time was not correlated to
adjusted ICU mortality (p = 0.20).
Conclusions: Prolonged emergency department to ICU time
(> 2.4hr) is ass
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