Systematic review of individual-level, community-level, and healthcare system-level factors contributing to socioeconomic differences in healthcare utilisation in OECD countries with universal health coverage

Objectives Countries with universal health coverage (UHC) strive for equal access for equal needs without users getting into financial distress. However, differences in healthcare utilisation (HCU) between socioeconomic groups have been reported in countries with UHC. This systematic review provides an overview individual-level, community-level, and system-level factors contributing to socioeconomic status-related differences in HCU (SES differences in HCU).Design Systematic review following the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) guidelines. The review protocol was published in advance.Data sources Embase, PubMed, Web of Science, Scopus, Econlit, and PsycInfo were searched on 9 March 2021 and 9 November 2022.Eligibility criteria Studies that quantified the contribution of one or more factors to SES difference in HCU in OECD countries with UHC.Data extraction and synthesis Studies were screened for eligibility by two independent reviewers. Data were extracted using a predeveloped data-extraction form. Risk of bias (ROB) was assessed using a tailored version of Hoy’s ROB-tool. Findings were categorised according to level and a framework describing the pathway of HCU.Results Of the 7172 articles screened, 314 were included in the review. 64% of the studies adjusted for differences in health needs between socioeconomic groups. The contribution of sex (53%), age (48%), financial situation (25%), and education (22%) to SES differences in HCU were studied most frequently. For most factors, mixed results were found regarding the direction of the contribution to SES differences in HCU.Conclusions SES differences in HCU extensively correlated to factors besides health needs, suggesting that equal access for equal needs is not consistently accomplished. The contribution of factors seemed highly context dependent as no unequivocal patterns were found of how they contributed to SES differences in HCU. Most studies examined the contribution of individual-level factors to SES differences in HCU, leaving the influence of healthcare system-level characteristics relatively unexplored

From test to rest:Evaluating socioeconomic differences along the COVID-19 care pathway in the Netherlands

IntroductionThe COVID-19 pandemic exacerbated healthcare needs and caused excess mortality, especially among lower socioeconomic groups. This study describes the emergence of socioeconomic differences along the COVID-19 pathway of testing, healthcare use and mortality in the Netherlands.MethodologyThis retrospective observational Dutch population-based study combined individual-level registry data from June 2020 to December 2020 on personal socioeconomic characteristics, COVID-19 administered tests, test results, general practitioner (GP) consultations, hospital admissions, Intensive Care Unit (ICU) admissions and mortality. For each outcome measure, relative differences between income groups were estimated using log-link binomial regression models. Furthermore, regression models explained socioeconomic differences in COVID-19 mortality by differences in ICU/hospital admissions, test administration and test results.ResultsAmong the Dutch population, the lowest income group had a lower test probability (RR = 0.61) and lower risk of testing positive (RR = 0.77) compared to the highest income group. However, among individuals with at least one administered COVID-19 test, the lowest income group had a higher risk of testing positive (RR = 1.40). The likelihood of hospital admissions and ICU admissions were higher for low income groups (RR = 2.11 and RR = 2.46, respectively). The lowest income group had an almost four times higher risk of dying from COVID-19 (RR = 3.85), which could partly be explained by a higher risk of hospitalization and ICU admission, rather than differences in test administration or result.DiscussionOur findings indicated that socioeconomic differences became more pronounced at each step of the care pathway, culminating to a large gap in mortality. This underlines the need for enhancing social security and well-being policies and incorporation of health equity in pandemic preparedness plans

Aanbod van zelftesten in Nederland

Met behulp van zelftesten kunnen consumenten inzicht krijgen in risico op ziekte, gepersonaliseerde leefstijladviezen of zelfs trachten een diagnose te stellen. Voorstanders van zelftesten pleiten voor zaken als een toename in privacy en vroegdiagnostiek, daar waar tegenstanders bijvoorbeeld de risico’s en kosten van vals-negatieven en -positieven sterk benadrukken (1, 2, 3). Huisartsen hebben aangegeven niet vaak patiënten te zien die een zelftest hebben uitgevoerd, maar hebben wel behoefte aan een verbetering in de informatievoorziening rondom zelftesten (4). Een overzicht van het huidige aanbod van zelftesten kan helpen om meer informatie over het aanbod te verzamelen, en de impact van de markt te verkennen/duiden

Identification of Distinct Unmutated Chronic Lymphocytic Leukemia Subsets in Mice Based on Their T Cell Dependency

Chronic lymphocytic leukemia (CLL) can be divided into prognostically distinct subsets with stereotyped or non-stereotyped, mutated or unmutated B cell receptors (BCRs). Individual subsets vary in antigen specificity and origin, but the impact of antigenic pressure on the CLL BCR repertoire remains unknown. Here, we employed IgH.TEμ mice that spontaneously develop CLL, expressing mostly unmutated BCRs of which ~35% harbor VH11-2/Vκ14-126 and recognize phosphatidylcholine. Proportions of VH11/Vκ14-expressing CLL were increased in the absence of functional germinal centers in IgH.TEμ mice deficient for CD40L or activation-induced cytidine deaminase. Conversely, in vivo T cell-dependent immunization decreased the proportions of VH11/Vκ14-expressing CLL. Furthermore, CLL onset was accelerated by enhanced BCR signaling in Siglec-G−/− mice or in mice expressing constitutively active Bruton's tyrosine kinase. Transcriptional profiling revealed that VH11 and non-VH11 CLL differed in the upregulation of specific pathways implicated in cell signaling and metabolism. Interestingly, principal component analyses using the 148 differentially expressed genes revealed that VH11 and non-VH11 CLL clustered with BCR-stimulated and anti-CD40-stimulated B cells, respectively. We identified an expression signature consisting of 13 genes that were differentially expressed in a larger panel of T cell-dependent non-VH11 CLL compared with T cell-independent VH11/Vκ14 or mutated IgH.TEμ CLL. Parallel differences in the expression of these 13 signature genes were observed between heterogeneous and stereotypic human unmutated CLL. Our findings provide evidence for two distinct unmutated CLL subsets with a specific transcriptional signature: one is T cell-independent and B-1 cell-derived while the other arises upon antigen stimulation in the context of T-cell help

Integrating transposable elements in the 3D genome

Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome

Butyrate inhibits human mast cell activation via epigenetic regulation of FcεRI-mediated signaling

Background: Short-chain fatty acids (SCFAs) are fermented dietary components that regulate immune responses, promote colonic health, and suppress mast cell–mediated diseases. However, the effects of SCFAs on human mast cell function, including the underlying mechanisms, remain unclear. Here, we investigated the effects of the SCFAs (acetate, propionate, and butyrate) on mast cell–mediated pathology and human mast cell activation, including the molecular mechanisms involved. Method: Precision-cut lung slices (PCLS) of allergen-exposed guinea pigs were used to assess the effects of butyrate on allergic airway contraction. Human and mouse mast cells were co-cultured with SCFAs and assessed for degranulation after IgE- or non–IgE-mediated stimulation. The underlying mechanisms involved were investigated using knockout mice, small molecule inhibitors/agonists, and genomics assays. Results: Butyrate treatment inhibited allergen-induced histamine release and airway contraction in guinea pig PCLS. Propionate and butyrate, but not acetate, inhibited IgE- and non–IgE-mediated human or mouse mast cell degranulation in a concentration-dependent manner. Notably, these effects were independent of the stimulation of SCFA receptors GPR41, GPR43, or PPAR, but instead were associated with inhibition of histone deacetylases. Transcriptome analyses revealed butyrate-induced downregulation of the tyrosine kinases BTK, SYK, and LAT, critical transducers of FcεRI-mediated signals that are essential for mast cell activation. Epigenome analyses indicated that butyrate redistributed global histone acetylation in human mast cells, including significantly decreased acetylation at the BTK, SYK, and LAT promoter regions. Conclusion: Known health benefits of SCFAs in allergic disease can, at least in part, be explained by epigenetic suppression of human mast cell activation

Control of developmentally primed erythroid genes by combinatorial co-repressor actions

How transcription factors (TFs) cooperate within large protein complexes to allow rapid modulation of gene expression during development is still largely unknown. Here we show that the key haematopoietic LIM-domain-binding protein-1 (LDB1) TF complex contains several activator and repressor components that together maintain an erythroid-specific gene expression programme primed for rapid activation until differentiation is induced. A combination of proteomics, functional genomics and in vivo studies presented here identifies known and novel co-repressors, most notably the ETO2 and IRF2BP2 proteins, involved in maintaining this primed state. The ETO2-IRF2BP2 axis, interacting with the NCOR1/SMRT co-repressor complex, suppresses the expression of the vast majority of archetypical erythroid genes and pathways until its decommissioning at the onset of terminal erythroid differentiation. Our experiments demonstrate that multimeric regulatory complexes feature a dynamic interplay between activating and repressing components that determines lineage-specific gene expression and cellular differentiation

Changes in the ceIl membrane of Lactobacillus bulgaricus during storage following freeze-drying

The mechanism of inactivation of freeze-dried Lactobacillus bulgaricus during storage in maltodextrin under controlled humidity was investigated. Evidence is presented supporting the hypothesis that membrane damage occurs during storage. A study on the lipid composition of the cells by gas chromatography showed a decrease in the unsaturated and saturated fatty acid content of the cell. Further evidence indicating membrane damage includes a decrease in membrane bound proton-translocating ATPase activity

Estrogen receptor-α recruits P-TEFb to overcome transcriptional pausing in intron 1 of the MYB gene

The MYB proto-oncogene is expressed in most estrogen receptor-positive (ERα +) breast tumors and cell lines. Expression of MYB is controlled, in breast cancer and other cell types, by a transcriptional pausing mechanism involving an attenuation site located ∼1.7kb downstream from the transcription start site. In breast cancer cells, ligand-bound ERα binds close to, and drives transcription beyond this attenuation site, allowing synthesis of complete transcripts. However, little is known, in general, about the factors involved in relieving transcriptional attenuation, or specifically how ERα coordinates such factors to promote transcriptional elongation. Using cyclin dependent kinase 9 (CDK9) inhibitors, reporter gene assays and measurements of total and intronic MYB transcription, we show that functionally active CDK9 is required for estrogen-dependent transcriptional elongation. We further show by ChIP and co-immunoprecipitation studies that the P-TEFb complex (CDK9/CyclinT1) is recruited to the attenuation region by ligand-bound ERα, resulting in increased RNA polymerase II Ser-2 phosphorylation. These data provide new insights into MYB regulation, and given the critical roles of MYB in tumorigenesis, suggest targeting MYB elongation as potential therapeutic strategy