Методичні підходи до оцінки ефективності функціонування ринку праці в аграрному секторі економіки

Ціль статті - визначити методичні підходи до оцінки ефективності функціонування ринку праці в аграрному секторі економіки на сучасному етапі

Necrotising enterocolitis and mortality in preterm infants after introduction of probiotics: A quasi-experimental study

Evidence on the clinical effectiveness of probiotics in the prevention of necrotising enterocolitis (NEC) in preterm infants is conflicting and cohort studies lacked adjustment for time trend and feeding type. This study investigated the association between the introduction of routine probiotics (Lactobacillus acidophilus and Bifidobacterium bifidum; Infloran ®) on the primary outcome 'NEC or death'. Preterm infants (gestational age <32 weeks or birth weight <1500 gram) admitted before (Jan 2008-Sep 2012; n = 1288) and after (Oct 2012-Dec 2014; n = 673) introduction of probiotics were compared. Interrupted time series logistic regression models were adjusted for confounders, effect modification by feeding type, seasonality and underlying temporal trends. Unadjusted and adjusted analyses showed no difference in 'NEC or death' between the two periods. The overall incidence of NEC declined from 7.8% to 5.1% (OR 0.63, 95% CI 0.42-0.93, p = 0.02), which was not statistically significant in the adjusted models. Introduction of probiotics was associated with a reduced adjusted odds for 'NEC or sepsis or death' in exclusively breastmilk-fed infants (OR 0.43, 95% CI 0.21-0.93, p = 0.03) only. We conclude that introduction of probiotics was not associated with a reduction in 'NEC or death' and that type of feeding seems to modify the effects of probiotics

The AMC Linear Disability Score project in a population requiring residential care: psychometric properties

BACKGROUND: Currently there is a lot of interest in the flexible framework offered by item banks for measuring patient relevant outcomes, including functional status. However, there are few item banks, which have been developed to quantify functional status, as expressed by the ability to perform activities of daily life. METHOD: This paper examines the psychometric properties of the AMC Linear Disability Score (ALDS) project item bank using an item response theory model and full information factor analysis. Data were collected from 555 respondents on a total of 160 items. RESULTS: Following the analysis, 79 items remained in the item bank. The remaining 81 items were excluded because of: difficulties in presentation (1 item); low levels of variation in response pattern (28 items); significant differences in measurement characteristics for males and females or for respondents under or over 85 years old (26 items); or lack of model fit to the data at item level (26 items). CONCLUSIONS: It is conceivable that the item bank will have different measurement characteristics for other patient or demographic populations. However, these results indicate that the ALDS item bank has sound psychometric properties for respondents in residential care settings and could form a stable base for measuring functional status in a range of situations, including the implementation of computerised adaptive testing of functional status

Homocysteine, S-adenosylmethionine and S-adenosylhomocysteine are associated with retinal microvascular abnormalities: the Hoorn Study

The aim of the present study was to investigate the relationship between homocysteine and homocysteine metabolism components and retinal microvascular disorders in subjects with and without Type 2 diabetes. In this population-based study of 256 participants, aged 60-85 years, we determined total plasma homocysteine, SAM (S-adenosylmethionine) and SAH (S-adenosylhomocysteine) in plasma and erythrocytes, total folate in serum and erythrocytes, 5-MTHF (5-methyltetrahydrofolate), and vitamins B12 and B6. Participants were examined ophthalmologically by means of indirect funduscopy and two-field 45° fundus photography, and were graded for retinopathy and retinal sclerotic vessel abnormalities. A computer-assisted method was used to measure retinal vessel diameters. Total plasma homocysteine was inversely associated with retinal arteriolar diameters {standardized β, -0.20 [95% CI (confidence interval), -0.33 to - 0.07]} or a decrease of 3.78 μm CRAEs (central retinal arteriolar equivalents) per 1 S.D. increase in homocysteine level (= 4.6 μmol/l). In addition, the SAM/SAH ratio in plasma was inversely associated with retinal sclerotic vessel abnormalities and retinopathy [odds ratios, 0.61 (95% CI, 0.39-0.96) and 0.50 (95% CI, 0.30-0.83) per 1 S.D. respectively]. The associations were independent of age, sex, glucose tolerance status, other homocysteine metabolism components and cardiovascular risk factors. In conclusion, the results of the present study support the concept that total plasma homocysteine and a low SAM/SAH ratio in plasma, which may reflect reduced transmethylation reactions, may contribute to the pathogenesis of (retinal) microangiopathy. © The Authors

Pathways Related to NLRP3 Inflammasome Activation Induced by Gold Nanorods

Gold; Inflammation; NanorodOro; Inflamación; NanorodOr; Inflamació; NanorodThe widespread and increasing use of engineered nanomaterials (ENM) increases the risk of human exposure, generating concern that ENM may provoke adverse health effects. In this respect, their physicochemical characteristics are critical. The immune system may respond to ENM through inflammatory reactions. The NLRP3 inflammasome responds to a wide range of ENM, and its activation is associated with various inflammatory diseases. Recently, anisotropic ENM have become of increasing interest, but knowledge of their effects on the immune system is still limited. The objective of the study was to compare the effects of gold ENM of different shapes on NLRP3 inflammasome activation and related signalling pathways. Differentiated THP-1 cells (wildtype, ASC- or NLRP3-deficient), were exposed to PEGylated gold nanorods, nanostars, and nanospheres, and, thus, also different surface chemistries, to assess NLRP3 inflammasome activation. Next, the exposed cells were subjected to gene expression analysis. Nanorods, but not nanostars or nanospheres, showed NLRP3 inflammasome activation. ASC- or NLRP3-deficient cells did not show this effect. Gene Set Enrichment Analysis revealed that gold nanorod-induced NLRP3 inflammasome activation was accompanied by downregulated sterol/cholesterol biosynthesis, oxidative phosphorylation, and purinergic receptor signalling. At the level of individual genes, downregulation of Paraoxonase-2, a protein that controls oxidative stress, was most notable. In conclusion, the shape and surface chemistry of gold nanoparticles determine NLRP3 inflammasome activation. Future studies should include particle uptake and intracellular localization.This research was funded by the EU FP7 project FutureNanoNeeds (GA N° 604602), RIVM, and VITO

The Academic Medical Center Linear Disability Score (ALDS) item bank: item response theory analysis in a mixed patient population

BACKGROUND: Currently, there is a lot of interest in the flexible framework offered by item banks for measuring patient relevant outcomes. However, there are few item banks, which have been developed to quantify functional status, as expressed by the ability to perform activities of daily life. This paper examines the measurement properties of the Academic Medical Center linear disability score item bank in a mixed population. METHODS: This paper uses item response theory to analyse data on 115 of 170 items from a total of 1002 respondents. These were: 551 (55%) residents of supported housing, residential care or nursing homes; 235 (23%) patients with chronic pain; 127 (13%) inpatients on a neurology ward following a stroke; and 89 (9%) patients suffering from Parkinson's disease. RESULTS: Of the 170 items, 115 were judged to be clinically relevant. Of these 115 items, 77 were retained in the item bank following the item response theory analysis. Of the 38 items that were excluded from the item bank, 24 had either been presented to fewer than 200 respondents or had fewer than 10% or more than 90% of responses in the category 'can carry out'. A further 11 items had different measurement properties for younger and older or for male and female respondents. Finally, 3 items were excluded because the item response theory model did not fit the data. CONCLUSION: The Academic Medical Center linear disability score item bank has promising measurement characteristics for the mixed patient population described in this paper. Further studies will be needed to examine the measurement properties of the item bank in other populations

Biomarker Potential of Interleukin-6 in Differentiating Necrotizing Enterocolitis from Late-Onset Sepsis in Neonates Born Preterm

Objective: Interleukin-6 (IL-6) is an early biomarker for sepsis and necrotizing enterocolitis (NEC). We assessed IL-6's ability to differentiate between late-onset sepsis (LOS) and NEC and between medical and surgical NEC. Study design: This retrospective cohort study included infants born preterm (birth weight &lt;1500 g, gestational age &lt;32 weeks) with ≥1 episodes of suspected late-onset sepsis (sLOS) between 2018 and 2023. Plasma IL-6 levels at sLOS onset were analyzed. Infants were grouped into (1) control (no sepsis/NEC), (2) LOS (culture negative/positive sepsis), or (3) NEC (medical/surgical), on the basis of the greatest classification of their observed episodes. IL-6's predictive value (alone and in combination with C-reactive protein) for sLOS outcomes was assessed with receiver operating characteristic analysis, with the area under the curve (AUC) quantifying its discriminative quality. Results: sLOS was observed in 421 infants (670 episodes); 131 (31%) had no LOS or NEC, 225 (53%) had LOS without NEC, and 65 (15%) had NEC. Median IL-6 values significantly differed between all groups, with highest in infants with NEC. The odds of NEC over LOS increased by a factor of 1.53 (95% CI 1.42-1.65, P &lt; .001) for every doubling of IL-measurements. IL-6 was not associated with the odds of surgical NEC compared with medical NEC. IL-6's ability to distinguish NEC from LOS was moderate (AUC 0.73). IL-6 combined with C-reactive protein (AUC 0.64) showed poor discriminative ability. Conclusions: Although elevated IL-6 levels are associated with greater odds of having NEC instead of LOS, the moderate predictive value suggests that IL-6 alone may not be sufficient for accurate early diagnosis or differentiation.</p

Inhibition of CYP2D6 with low dose (5 mg) paroxetine in patients with high 10-hydroxynortriptyline serum levels-A prospective pharmacokinetic study

The antidepressant nortriptyline is metabolized by cytochrome P450 2D6 (CYP2D6) to the less active and more cardiotoxic drug metabolite, 10-hydroxynortriptyline. High serum levels of this metabolite (>200 μg/L) may lead to withdrawal of nortriptyline therapy. Adding CYP2D6 inhibitors reduce the metabolic activity of CYP2D6 (phenoconversion) and so decrease the forming of hydroxynortriptyline. In this study, 5 mg paroxetine is administered to patients with high hydroxynortriptyline concentrations (>200 μg/L). The shift in number of patients to therapeutic nortriptyline (50-150 μg/L) and safe hydroxynortriptyline (<200 μg/L) concentrations, and the degree of phenoconversion, expressed as the change in ratio nortriptyline/hydroxynortriptyline concentrations before and after paroxetine addition, are prospectively observed and described. After paroxetine addition, 12 patients (80%) had therapeutic nortriptyline and safe hydroxynortriptyline concentrations. Hydroxynortriptyline concentrations decreased in all patients. The average nortriptyline/hydroxynortriptyline concentrations ratio increased from 0.32 to 0.59. This study shows that 5 mg paroxetine addition is able to lower high hydroxynortriptyline serum levels to safe ranges

Nano(bio)Materials Do Not Affect Macrophage Phenotype-A Study Conducted by the REFINE Project.

Macrophages are well known for their involvement in the biocompatibility, as well as biodistribution, of nano(bio)materials. Although there are a number of rodent cell lines, they may not fully recapitulate primary cell responses, particularly those of human cells. Isolation of tissue-resident macrophages from humans is difficult and may result in insufficient cells with which to determine the possible interaction with nano(bio)materials. Isolation of primary human monocytes and differentiation to monocyte-derived macrophages may provide a useful tool with which to further study these interactions. To that end, we developed a standard operating procedure for this differentiation, as part of the Regulatory Science Framework for Nano(bio)material-based Medical Products and Devices (REFINE) project, and used it to measure the secretion of bioactive molecules from M1 and M2 differentiated monocytes in response to model nano(bio)materials, following an initial assessment of pyrogenic contamination, which may confound potential observations. The SOP was deployed in two partner institutions with broadly similar results. The work presented here shows the utility of this assay but highlights the relevance of donor variability in responses to nano(bio)materials. Whilst donor variability can provide some logistical challenges to the application of such assays, this variability is much closer to the heterogeneous cells that are present in vivo, compared to homogeneous non-human cell lines