•Have assessed use of evolutionary algorithms in 1D- and 2D-LC method development.•Have compared 3 algorithm classes and benchmarked them against plain grid search.•The optimised evolution strategies ...(ES) algorithm is identified as the best performing.•Difference between algorithms grows with difficulty of the separation problem.
We report on the performance of three classes of evolutionary algorithms (genetic algorithms (GA), evolution strategies (ES) and covariance matrix adaptation evolution strategy (CMA-ES)) as a means to enhance searches in the method development spaces of 1D- and 2D-chromatography. After optimisation of the design parameters of the different algorithms, they were benchmarked against the performance of a plain grid search. It was found that all three classes significantly outperform the plain grid search, especially in terms of the number of search runs needed to achieve a given separation quality. As soon as more than 100 search runs are needed, the ES algorithm clearly outperforms the GA and CMA-ES algorithms, with the latter performing very well for short searches (<50 search runs) but being susceptible to convergence to local optima for longer searches. It was also found that the performance of the ES and GA algorithms, as well as the grid search, follow a hyperbolic law in the large search run number limit, such that the convergence rate parameter of this hyperbolic function can be used to quantify the difference in required number of search runs for these algorithms. In agreement with one's physical expectations, it was also found that the general advantage of the GA and ES algorithms over the grid search, as well as their mutual performance differences, grow with increasing difficulty of the separation problem.
Abstract Background Despite the high prevalence of neuropathic pain, treating this neurological disease remains challenging, given the limited efficacy and numerous side effects associated with ...current therapies. The complexity in patient management is largely attributed to an incomplete understanding of the underlying pathological mechanisms. Central sensitization, that refers to the adaptation of the central nervous system to persistent inflammation and heightened excitatory transmission within pain pathways, stands as a significant contributor to persistent pain. Considering the role of the cystine/glutamate exchanger (also designated as system x c − ) in modulating glutamate transmission and in supporting neuroinflammatory responses, we investigated the contribution of this exchanger in the development of neuropathic pain. Methods We examined the implication of system x c − by evaluating changes in the expression/activity of this exchanger in the dorsal spinal cord of mice after unilateral partial sciatic nerve ligation. In this surgical model of neuropathic pain, we also examined the consequence of the genetic suppression of system x c − (using mice lacking the system x c − specific subunit xCT) or its pharmacological manipulation (using the pharmacological inhibitor sulfasalazine) on the pain-associated behavioral responses. Finally, we assessed the glial activation and the inflammatory response in the spinal cord by measuring mRNA and protein levels of GFAP and selected M1 and M2 microglial markers. Results The sciatic nerve lesion was found to upregulate system x c − at the spinal level. The genetic deletion of xCT attenuated both the amplitude and the duration of the pain sensitization after nerve surgery, as evidenced by reduced responses to mechanical and thermal stimuli, and this was accompanied by reduced glial activation. Consistently, pharmacological inhibition of system x c − had an analgesic effect in lesioned mice. Conclusion Together, these observations provide evidence for a role of system x c − in the biochemical processes underlying central sensitization. We propose that the reduced hypersensitivity observed in the transgenic mice lacking xCT or in sulfasalazine-treated mice is mediated by a reduced gliosis in the lumbar spinal cord and/or a shift in microglial M1/M2 polarization towards an anti-inflammatory phenotype in the absence of system x c − . These findings suggest that drugs targeting system x c − could contribute to prevent or reduce neuropathic pain.
Summary
Background
Integrating mobile health (mHealth) into paediatric obesity treatment can provide opportunities for more personalized and lifetime treatment. However, high attrition rates pose a ...significant challenge. The current study attempts to better understand attrition by exploring (1) attrition rates of a monitoring mHealth application for usage over 14 days and (2) testing predictors of attrition in adolescents with obesity.
Methods
Participants were 69 adolescents between 12 and 16 years old who engaged in a multidisciplinary obesity treatment centre (either outpatient or inpatient) in two countries (Belgium and France). To assess the attrition rates, frequency distributions were used. To test the predictors of attrition, zero‐inflated negative binomial regression was performed.
Results
Attrition rates were high, in the outpatient group, more than half of the participants (53.3%) used the app for only 0–7 days. In the inpatient group, this percentage was 24.1%. Only deficits in initiating (a component of executive functions) were a negative predictor of attrition, indicating that deficits in initiating lead to lower attrition rates.
Conclusions
This study provides evidence for high attrition rates in mHealth interventions for adolescents with obesity and was the first to investigate psychological predictors of attrition to an mHealth monitoring tool in adolescents with obesity in treatment. Findings regarding predictors of attrition should be approached with caution due to the small sample size.
Disruption of the glutamatergic homeostasis is commonly observed in neurological diseases and has been frequently correlated with the altered expression and/or function of astrocytic high-affinity ...glutamate transporters. There is, however, a growing interest for the role of the cystine-glutamate exchanger system x
c
–
in controlling glutamate transmission. This exchanger is predominantly expressed in glial cells, especially in microglia and astrocytes, and its dysregulation has been documented in diverse neurological conditions. While most studies have focused on measuring the expression of its specific subunit xCT by RT-qPCR or by Western blotting, the activity of this exchanger in tissue samples remains poorly examined. Indeed, the reported use of sulfur- and carbon-radiolabeled cystine in uptake assays shows several drawbacks related to its short radioactive half-life and its relatively high cost. We here report on the elaborate validation of a method using tritiated glutamate as a substrate for the reversed transport mediated by system x
c
–
. The uptake assay was validated in primary cultured astrocytes, in transfected cells as well as in crude synaptosomes obtained from fresh nervous tissue samples. Working in buffers containing defined concentrations of Na
+
, allowed us to differentiate the glutamate uptake supported by system x
c
–
or by high-affinity glutamate transporters, as confirmed by using selective pharmacological inhibitors. The specificity was further demonstrated in primary astrocyte cultures from transgenic mice lacking xCT or in cell lines where xCT expression was genetically induced or reduced. As such, this assay appears to be a robust and cost-efficient solution to investigate the activity of this exchanger in physiological and pathological conditions. It also provides a reliable tool for the screening and characterization of new system x
c
–
inhibitors which have been frequently cited as valuable drugs for nervous disorders and cancer.
Stent thrombosis (ST) is a serious complication following coronary stenting. Intravascular optical coherence tomography (OCT) may provide insights into mechanistic processes leading to ST. We ...performed a prospective, multicenter study to evaluate OCT findings in patients with ST.
Consecutive patients presenting with ST were prospectively enrolled in a registry by using a centralized telephone registration system. After angiographic confirmation of ST, OCT imaging of the culprit vessel was performed with frequency domain OCT. Clinical data were collected according to a standardized protocol. OCT acquisitions were analyzed at a core laboratory. Dominant and contributing findings were adjudicated by an imaging adjudication committee.
Two hundred thirty-one patients presenting with ST underwent OCT imaging; 14 (6.1%) had image quality precluding further analysis. Of the remaining patients, 62 (28.6%) and 155 (71.4%) presented with early and late/very late ST, respectively. The underlying stent type was a new-generation drug-eluting stent in 50.3%. Mean reference vessel diameter was 2.9±0.6 mm and mean reference vessel area was 6.8±2.6 mm
. Stent underexpansion (stent expansion index <0.8) was observed in 44.4% of patients. The predicted average probability (95% confidence interval) that any frame had uncovered (or thrombus-covered) struts was 99.3% (96.1-99.9), 96.6% (92.4-98.5), 34.3% (15.0-60.7), and 9.6% (6.2-14.5) and malapposed struts was 21.8% (8.4-45.6), 8.5% (4.6-15.3), 6.7% (2.5-16.3), and 2.0% (1.2-3.3) for acute, subacute, late, and very late ST, respectively. The most common dominant finding adjudicated for acute ST was uncovered struts (66.7% of cases); for subacute ST, the most common dominant finding was uncovered struts (61.7%) and underexpansion (25.5%); for late ST, the most common dominant finding was uncovered struts (33.3%) and severe restenosis (19.1%); and for very late ST, the most common dominant finding was neoatherosclerosis (31.3%) and uncovered struts (20.2%). In patients presenting very late ST, uncovered stent struts were a common dominant finding in drug-eluting stents, and neoatherosclerosis was a common dominant finding in bare metal stents.
In patients with ST, uncovered and malapposed struts were frequently observed with the incidence of both decreasing with longer time intervals between stent implantation and presentation. The most frequent dominant observation varied according to time intervals from index stenting: uncovered struts and underexpansion in acute/subacute ST and neoatherosclerosis and uncovered struts in late/very late ST.
Mental healthcare is an important component in societies' response to mental health problems. Although the World Health Organization highlights availability, accessibility, acceptability and quality ...of healthcare as important cornerstones, many Europeans lack access to mental healthcare of high quality. Qualitative studies exploring mental healthcare from the perspective of people with lived experiences would add to previous research and knowledge by enabling in-depth understanding of mental healthcare users, which may be of significance for the development of mental healthcare. Therefore, the aim of the current study was to describe experiences of mental healthcare among adult Europeans with mental health problems.
In total, 50 participants with experiences of various mental health problems were recruited for separate focus group interviews in each country. They had experiences from both the private and public sectors, and with in- and outpatient mental healthcare. The focus group interviews (N = 7) were audio recorded, transcribed verbatim and analysed through thematic analysis. The analysis yielded five themes and 13 subthemes.
The theme Seeking and trying to find help contained three subthemes describing personal thresholds for seeking professional help, not knowing where to get help, and the importance of receiving help promptly. The theme Awaiting assessment and treatment contained two subthemes including feelings of being prioritized or not and feelings of being abandoned during the often-lengthy referral process. The theme Treatment: a plan with individual parts contained three subthemes consisting of demands for tailored treatment plans in combination with medications and human resources and agreement on treatment. The theme Continuous and respectful care relationship contained two subthemes describing the importance of continuous care relationships characterised by empathy and respect. The theme Suggestions for improvements contained three subthemes highlighting an urge to facilitate care contacts and to increase awareness of mental health problems and a wish to be seen as an individual with potential.
Facilitating contacts with mental healthcare, a steady contact during the referral process, tailored treatment and empathy and respect are important aspects in efforts to improve mental healthcare. Recommendations included development of collaborative practices between stakeholders in order to increase general societal awareness of mental health problems.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The benefit of reperfusion therapies for ST-elevation acute myocardial infarction (STEMI) is limited by post-infarction left-ventricular (LV) dysfunction. Our aim was to investigate the effect of ...autologous bone marrow-derived stem cell (BMSC) transfer in the infarct-related artery on LV function and structure.
We did a randomised, double-blind, placebo-controlled study in 67 patients from whom we harvested bone marrow 1 day after successful percutaneous coronary intervention for STEMI. We assigned patients optimum medical treatment and infusion of placebo (n=34) or BMSC (n=33). Our primary endpoint was the increase in LV ejection fraction and our secondary endpoints were change in infarct size and regional LV function at 4 months' follow-up, all assessed by MRI. We assessed changes in myocardial perfusion and oxidative metabolism with serial 1-
11Cacetate PET. Analyses were per protocol. This study is registered with
clinicaltrials.gov, number NCT00264316.
Mean global LV ejection fraction 4 days after percutaneous coronary intervention was 46·9% (SD 8·2) in controls and 48·5% (7·2) in BMSC patients, and increased after 4 months to 49·1% (10·7) and 51·8% (8·8; OR for treatment effect 1·036, 95% CI 0·961–1·118, p=0·36). Compared with placebo infusion, BMSC transfer was associated with a significant reduction in myocardial infarct size (BMSC treatment effect 28%, p=0·036) and a better recovery of regional systolic function. Myocardial perfusion and metabolism increased similarly in both groups. We noted no complications associated with BMSC transfer and all but one patient in the BMSC group completed the 4 months' follow-up.
Intracoronary transfer of autologous bone marrow cells within 24 h of optimum reperfusion therapy does not augment recovery of global LV function after myocardial infarction, but could favourably affect infarct remodelling.
IntroductionThere is a lack of distinct and measurable outcomes in psychiatric and/or mental health nursing which negatively impacts guiding clinical practice, assessing evidence-based nursing ...interventions, ensuring future-proof nursing education and establishing visibility as a profession and discipline. Psychiatric and/or mental health nursing struggle to demonstrate patient-reported outcomes to assess the effectiveness of their practice. A systematic review that summarising patient-reported outcomes, associated factors, measured nursing care/interventions and used measurement scales of psychiatric and/or mental health nursing in the adult population in acute, intensive and forensic psychiatric wards in hospitals will capture important information on how care can be improved by better understanding what matters and what is important to patients themselves. This review can contribute to the design, planning, delivery and assessment of the quality of current and future nursing careMethods and analysisThis protocol follows the Cochrane methodological guidance on systematic reviews of interventions and The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol. The search strategy will be identified by consultations with clinical and methodological experts and by exploring the literature. The databases Ovid MEDLINE, CINAHL, EMBASE, APA PsychARTICLES, Web of Science and Scopus will be searched for all published studies. Studies will be screened and selected with criteria described in the population, intervention, control and outcomes format after a pilot test by two researchers. Studies will be screened in two stages: (1) title and abstract screening and (2) full-text screening. Data extraction and the quality assessment based on the Johanna Briggs Institute guidelines will be conducted by two researchers. Data will be presented in a narrative synthesis.Ethics and disseminationNo ethical approval is needed since all data are already publicly accessible. The results of this work will be published in a peer-reviewed scientific journal.PROSPERO registration numberCRD42023363806.
Alterations in the activity of the regulator of cell metabolism AMP-activated protein kinase (AMPK) have been reported in motor neurons from patients and animal models of amyotrophic lateral ...sclerosis (ALS). Considering the key role played by astrocytes in modulating energy metabolism in the nervous system and their compromised support towards neurons in ALS, we examined whether a putative alteration in AMPK expression/activity impacted astrocytic functions such as their metabolic plasticity and glutamate handling capacity. We found a reduced expression of AMPK mRNA in primary cultures of astrocytes derived from transgenic rats carrying an ALS-associated mutated superoxide dismutase (hSOD1G93A). The activation of AMPK after glucose deprivation was reduced in hSOD1G93A astrocytes compared to non-transgenic. This was accompanied by a lower increase in ATP levels and increased vulnerability to this insult, although the ATP production rate did not differ between the two cell types. Furthermore, soliciting the activity of glutamate transporters was found to induce similar AMPK activity in these cells. However, manipulation of AMPK activity did not influence glutamate transport. Together, these results suggest that the altered AMPK responsiveness in ALS might be context dependent and may compromise the metabolic adaptation of astrocytes in response to specific cellular stress.
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