Educational inequalities in self-rated health and emotional exhaustion among workers during the COVID-19 pandemic: a longitudinal study.

OBJECTIVE: This study aimed to investigate trends in educational inequalities in poor health and emotional exhaustion during the pandemic among workers, and differences in trends between men and women. METHODS: Five waves (2019-2021) from the longitudinal study 'the Netherlands Working Conditions Survey COVID-19 study' were used (response rates: 32-38%). Generalized logistic mixed models were used to estimate the changes in absolute and relative educational inequalities in poor health and emotional exhaustion for all workers (n = 12,479) and for men and women, separately. RESULTS: Low and intermediate educated workers reported more often poor health (OR 2.54; 95% CI 1.71-3.77 and OR 2.09; 95% CI 1.68-2.61, respectively) than high educated workers. Intermediate educated women (OR 0.49; 95% CI 0.37-0.64) reported less emotional exhaustion than high educated women, but no differences were observed among men. The prevalence of poor health first decreased across all educational levels until March 2021, and bounced back in November 2021. A similar pattern was found for emotional exhaustion, but for low and intermediate educated workers only. Relative educational inequalities in poor health reduced among men during the pandemic, and absolute differences decreased among men and women by 2.4-2.6%. Relative educational inequalities in emotional exhaustion widened among men only. Absolute differences in emotional exhaustion first increased among both men and women, but narrowed between the last two waves. DISCUSSION: Socioeconomic inequalities for poor self-rated health remained but narrowed in relative and absolute terms during the pandemic. With regard to emotional exhaustion, socioeconomic inequalities returned to pre-COVID-19 levels at the end of 2021.

Employers' attitude, intention, skills and barriers in relation to employment of vulnerable workers.

BACKGROUND: Little is known why some organizations employ vulnerable workers and others do not. OBJECTIVE: To explore the relationships between the attitude, intention, skills and barriers of employers and employment of vulnerable workers. METHODS: We included 5,601 inclusive organizations (≥1% of employees had a disability, was long-term unemployed or a school dropout) and 6,236 non-inclusive organizations of the Netherlands Employers Work Survey 2014-2019. We operationalized employer factors based on the Integrative Model of Behavioral Prediction as attitude (negative impact), intention (mission statement regarding social inclusion), skills (human resources policies and practices), and barriers (economic conditions and type of work). We used multivariate-adjusted logistic regression models. RESULTS: Compared to non-inclusive organizations, inclusive organizations had a more negative attitude (OR:0.81) and a stronger intention to employ vulnerable workers (OR:6.09). Regarding skills, inclusive organizations had more inclusive human resources practices (OR:4.83) and initiated more supporting human resources actions (OR:4.45). Also, they adapted more work conditions towards the needs of employees (OR:1.52), negotiated about work times and absenteeism (OR:1.49), and had general human resources practices on, for example, employability (OR:1.78). Inclusive organizations had less barriers reflected by better financial results (OR:1.32), more employment opportunities (OR:1.33) and more appropriate work tasks (OR:1.40). CONCLUSIONS: Overall, inclusive organizations reported more positive results on the employer factors of the Integrative Model of Behavioral Prediction, except for a more negative attitude. The more negative attitude might reflect a more realistic view on the efforts to employ vulnerable groups, and suggests that other unmeasured emotions and beliefs are more positive.

Switching solvent and enhancing analyte concentrations in small effluent fractions using in-column focusing.

A novel approach to achieve solvent switching and focusing of sub-column-volume analyte fractions in liquid chromatography is presented. By altering the temperature between loading and elution in back-flush mode, solvent transfer of analytes and focusing occurs, provided that the analytes exhibit temperature dependent retention on a given trap column. When retention on the trap decreases with increasing temperature, which is almost always the case, the loading of the trap-column takes place at a higher temperature than the elution. This principle is demonstrated using three small aromatic molecules (toluene, p-xylene and benzophenone) on a capillary monolithic column. On this column, the analytes show a traditional van't Hoff dependence on temperature with enthalpy effects of, -15, -16 and -18 kJ mol(-1), respectively, for a mobile phase of 25% acetonitrile in water. The column was loaded at 110 °C, cooled in an ice bath and eluted in back-flush mode at 0 °C. When operated in this way, the analytes are transferred from the loading solvent to the elution solvent, achieving solvent switching. Substantial focusing can also be obtained if the desorption solvent is stronger than the loading solvent.

PLGA nanoparticles and nanosuspensions with amphotericin B: Potent in vitro and in vivo alternatives to Fungizone and AmBisome.

This paper describes the development of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) and nanosuspensions with the polyene antibiotic amphotericin B (AmB). The nanoformulations were prepared using nanoprecipitation and were characterised with respect to size, zeta potential, morphology, drug crystallinity and content. Standard in vitro sensitivity tests were performed on MRC-5 cells, red blood cells, Leishmania infantum promastigotes and intracellular amastigotes and the fungal species Candida albicans, Aspergillus fumigatus and Trichophyton rubrum. The in vivo efficacy was assessed and compared to that of Fungizone and AmBisome in the acute A. fumigatus mouse model at a dose of 2.5 and 5.0mg/kg AmB equivalents. The developed AmB nanoformulations were equivalently or more effective against the different Leishmania stages and axenic fungi in comparison with the free drug. The in vitro biological activity, and especially hemolytic activity, clearly depended on the preparation parameters of the different nanoformulations. Further, we demonstrated that the superior in vitro antifungal activity could be extrapolated to the in vivo situation. At equivalent dose, the optimal AmB-loaded PLGA NP was about two times and the AmB nanosuspension about four times more efficacious in reducing the total burden than AmBisome. The developed AmB nanomedicines could represent potent and cost-effective alternatives to Fungizone and AmBisome.

Intracellular drug delivery in Leishmania-infected macrophages: Evaluation of saponin-loaded PLGA nanoparticles.

Drug delivery systems present an opportunity to potentiate the therapeutic effect of antileishmanial drugs. Colloidal carriers are rapidly cleared by the phagocytic cells of the reticuloendothelial system (RES), rendering them ideal vehicles for passive targeting of antileishmanials. This paper describes the development of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) for the antileishmanial saponin ß-aescin. NPs were prepared using the combined emulsification solvent evaporation/salting-out technique. Confocal microscopy was used to visualise the internalisation and intracellular trafficking of fluorescein- and nile red-labelled PLGA NPs in J774A.1 macrophages infected with GFP-transfected Leishmania donovani. The in vitro activity of aescin and aescin-loaded NPs on L. infantum was determined in the axenic model as well as in the ex vivo model. The developed PLGA NPs were monodispersed with Z(ave)<300 nm, exhibited negative zeta potentials and had relatively high drug loadings ranging from 5.80 to 8.68% w/w PLGA. The fluorescent NPs were internalised by the macrophages and trafficked towards the lysosomes after 2 h in vitro incubation. Co-localisation of the NPs and the parasite was not shown. A two-fold increase in activity was observed in the ex vivo macrophage model by encapsulating ß-aescin in PLGA NPs (IC(50), 0.48-0.76 µg/mL vs. 1.55 ± 0.32 µg/mL for the free drug).

PLGA nanoparticles loaded with the antileishmanial saponin ß-aescin: factor influence study and in vitro efficacy evaluation.

Colloidal carriers are known to improve the therapeutic index of the conventional drugs in the treatment of visceral leishmaniasis (VL) by decreasing their toxicity whilst maintaining or increasing therapeutic efficacy. This paper describes the development of poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) for the antileishmanial saponin ß-aescin. NPs were prepared by the W/O/W emulsification solvent evaporation technique and the influence of five preparation parameters on the NPs' size (Z(ave)), zeta potential and entrapment efficiency (EE%) was investigated using a 2(5-2) fractional factorial design. Cytotoxicity of aescin, aescin-loaded and blank PLGA NPs was evaluated in J774 macrophages and non-phagocytic MRC-5 cells, whereas antileishmanial activity was determined in the Leishmania infantum ex vivo model. The developed PLGA NPs were monodispersed with Z(ave)<500 nm and exhibited negative zeta potentials. The process variables 'surfactant primary emulsion', 'concentration aescin' and 'solvent evaporation rate' had a positive effect on EE%. Addition of Tween 80 to the inner aqueous phase rendered the primary emulsion more stable, which in its turn led to better saponin entrapment. The selectivity index (SI) towards the supporting host macrophages increased from 4 to 18 by treating the cells with aescin-loaded NPs instead of free ß-aescin. In conclusion, the in vitro results confirmed our hypothesis.

Solid lipid nanoparticle (SLN) formulations as a potential tool for the reduction of cytotoxicity of saponins.

The present pilot study explored the potential of solid lipid nanoparticles (SLN) to entrap saponins and reduce the membrane toxicity of these compounds. SLN composed of different types of solid lipid were prepared by the cold homogenisation technique. Combinations of anionic, cationic and non-ionic stabilisers were selected in order to obtain negatively, positively and neutrally charged SLN. Mean particle size and zeta potential of blank and saponin-loaded formulations were measured by Dynamic Light Scattering (DLS), Electrophoretic Light Scattering (ELS) and in vitro cytotoxicity on MRC-5 SV2 and J774 cells was assessed using a resazurin-based assay. The type of solid lipid used for the formulation influenced the mean particle size, while the zeta potential mainly depended on the kind of surfactant utilised. Blank SLN composed of hard fat and anionic or non-ionic surfactants did not result in cytotoxicity. After loading with saponin, the anionic hard fat SLN was found to be the optimal formulation.