Area-based comparison of risk factors and testing rates to improve sexual health care access:Cross-sectional population-based study in a Dutch multicultural area

Objectives Areas with high sexually transmitted infection (STI) testing rates may not require additional strategies to improve testing. However, it may be necessary to intervene in areas with elevated STI risk, but with low STI testing rates. We aimed to compare STI-related risk profiles and STI testing rates by geographical area to determine areas for improvement of sexual healthcare access.Design Cross-sectional population-based study.Setting Greater Rotterdam area, the Netherlands (2015–2019).Participants All residents aged 15–45 years. Individual population-based register data were matched with laboratory-based STI testing data of general practitioners (GPs) and the only sexual health centre (SHC).Outcome measures Postal code (PC) area-specific STI risk scores (based on age, migratory background, education level and urbanisation), STI testing rates and STI positivity.Results The study area consists of approximately 500 000 residents aged 15–45 years. Strong spatial variation in STI testing, STI positivity and STI risk was observed. PC area testing rate ranged from 5.2 to 114.9 tests per 1000 residents. Three PC clusters were identified based on STI risk and testing rate: (1) high–high; (2) high–low; (3) low, independently of testing rate. Clusters 1 and 2 had comparable STI-related risk and STI positivity, but the testing rate differed greatly (75.8 vs 33.2 per 1000 residents). Multivariable logistic regression analysis with generalised estimating equation was used to compare residents in cluster 1 and cluster 2. Compared with cluster 1, residents in cluster 2 more often did not have a migratory background, lived in less urbanised areas with higher median household income, and more distant from both GP and SHC.Conclusion The determinants associated with individuals living in areas with high STI-related risk scores and low testing rates provide leads for improvement of sexual healthcare access. Opportunities for further exploration include GP education, community-based testing and service (re)allocation

The roles of the general practitioner and sexual health centre in HIV testing:comparative insights and impact on HIV incidence rates in the Rotterdam area, the Netherlands - a cross-sectional population-based study

Background: Access to HIV testing is crucial for detection, linkage to treatment, and prevention. In less urbanised areas, reliance on general practitioners (GPs) for HIV testing is probable, as sexual health centres (SHC) are mostly located within urbanised areas. Limited insight into individuals undergoing HIV testing stems from sparse standard registration of demographics at GPs. This cross-sectional study aims (1) to assess and compare HIV testing at the GP and SHC, and (2) to assess population- and provider-specific HIV incidence. Methods: Individual HIV testing data of GPs and SHC were linked to population register data (aged ≥ 15 years, Rotterdam area, 2015–2019). We reported the proportion HIV tested, and compared GP and SHC testing rates with negative binomial generalised additive models. Data on new HIV diagnoses (2015–2019) from the Dutch HIV Monitoring Foundation relative to the population were used to assess HIV incidence. Results: The overall proportion HIV tested was 1.14% for all residents, ranging from 0.41% for ≥ 40-year-olds to 4.70% for Antilleans. The GP testing rate was generally higher than the SHC testing rate with an overall rate ratio (RR) of 1.61 (95% CI: 1.56–1.65), but not for 15-24-year-olds (RR: 0.81, 95% CI: 0.74–0.88). Large differences in HIV testing rate (1.36 to 39.47 per 1,000 residents) and GP-SHC ratio (RR: 0.23 to 7.24) by geographical area were observed. The GPs’ contribution in HIV testing was greater for GP in areas further away from the SHC. In general, population groups that are relatively often tested are also the groups with most diagnoses and highest incidence (e.g., men who have sex with men, non-western). The overall incidence was 10.55 per 100,000 residents, varying from 3.09 for heterosexual men/women to 24.04 for 25–29-year-olds. Conclusions: GPs have a pivotal role in HIV testing in less urbanised areas further away from the SHC, and among some population groups. A relatively high incidence often follows relatively high testing rates. Opportunities to improve HIV testing have been found for migrants, lower-educated individuals, in areas less urbanised areas and further away from GP/SHC. Strategies include additional targeted testing, via for example SHC branch locations and outreach activities.</p

A Family of Water Immiscible, Dipolar Aprotic, Diamide Solvents from Succinic Acid

Three dipolar aprotic solvents were designed to possess high dipolarity and low toxicity: N , N , N ', N '-tetrabutylsuccindiamide (TBSA), N , N '-diethyl- N , N '-dibutylsuccindiamide (EBSA), N , N '-dimethyl- N , N '-dibutylsuccindiamide (MBSA). They were synthesized catalytically using a K60 silica catalyst in a solventless system. Their water-immiscibility stands out as an unusual and useful property for dipolar aprotic solvents. They were tested in a model Heck reaction, metal-organic framework syntheses, and a selection of polymer solubility experiments where their performances were found to be comparable to traditional solvents. Furthermore, MBSA was found to be suitable for the production of an industrially-relevant membrane from polyethersulphone. An integrated approach involving in silico analysis based on available experimental information, prediction model outcomes and read across data, as well as a panel of in vitro reporter gene assays covering a broad range of toxicological endpoints was used to assess toxicity. These in silico and in vitro tests suggested no alarming indications of toxicity in the new solvents

Use of Short Tandem Repeat Sequences to Study Mycobacterium leprae in Leprosy Patients in Malawi and India

Molecular typing has provided an important tool for studies of many pathogens. Such methods could be particularly useful in studies of leprosy, given the many outstanding questions about the pathogenesis and epidemiology of this disease. The approach is particularly difficult with leprosy, however, because of the genetic homogeneity of M. leprae and our inability to culture it. This paper describes molecular epidemiological studies carried out on leprosy patients in Malawi and in India, using short tandem repeat sequences (STRS) as markers of M. leprae strains. It reveals evidence for continuous changes in these markers within individual patients over time, and for selection of different STRS-defined strains between different tissues (skin and nerve) in the same patient. Comparisons between patients collected under different circumstances reveal the uses and limitations of the approach—STRS analysis may in some circumstances provide a means to trace short transmission chains, but it does not provide a robust tool for distinguishing between relapse and reinfection. This encourages further work to identify genetic markers with different stability characteristics for incorporation into epidemiological studies of leprosy

Laboratory study on the mobility of major species in fly ash–brine co-disposal systems: up-flow percolation test

Apart from the generation of fly ash, brine (hyper-saline wastewater) is also a waste material generated in South African power stations as a result of water re-use. These waste materials contain major species such as Al, Si, Na, K, Ca, Mg, Cl and SO4. The co-disposal of fly ash and brine has been practiced by some power stations in South Africa with the aim of utilizing the fly ash to capture the salts in brine. The effect of the chemical interaction of the species contained in both fly ash and brine, when co-disposed, on the mobility of species in the fly ash–brine systems is the focus of this study. The up-flow percolation test was employed to determine the mobility of some major species in the fly ash–brine systems. The results of the analysed eluates from the up-flow percolation tests revealed that some species such as Al, Ca and Na were leached from the fly ash into the brine solution while some species such as Mg, Cl and SO4 were removed to some extent from the brine solution during the interaction with fly ash. The pH of the up-flow percolation systems was observed to play a significant role on the mobility of major species from the fly ash–brine systems. The study showed that some major species such as Mg, Cl and SO4 could be removed from brine solution using fly ash when certain amount of brine percolates through the ash.Web of Scienc

Cell-type specific RNA-Seq reveals novel roles and regulatory programs for terminally differentiated Dictyostelium cells

Abstract Background A major hallmark of multicellular evolution is increasing complexity by the evolution of new specialized cell types. During Dictyostelid evolution novel specialization occurred within taxon group 4. We here aim to retrace the nature and ancestry of the novel “cup” cells by comparing their transcriptome to that of other cell types. Results RNA-Seq was performed on purified mature spore, stalk and cup cells and on vegetative amoebas. Clustering and phylogenetic analyses showed that cup cells were most similar to stalk cells, suggesting that they share a common ancestor. The affinity between cup and stalk cells was also evident from promoter-reporter studies of newly identified cell-type genes, which revealed late expression in cups of many stalk genes. However, GO enrichment analysis reveal the unexpected prominence of GTPase mediated signalling in cup cells, in contrast to enrichment of autophagy and cell wall synthesis related transcripts in stalk cells. Combining the cell type RNA-Seq data with developmental expression profiles revealed complex expression dynamics in each cell type as well as genes exclusively expressed during terminal differentiation. Most notable were nine related hssA-like genes that were highly and exclusively expressed in cup cells. Conclusions This study reveals the unique transcriptomes of the mature cup, stalk and spore cells of D. discoideum and provides insight into the ancestry of cup cells and roles in signalling that were not previously realized. The data presented in this study will serve as an important resource for future studies into the regulation and evolution of cell type specialization

Novel (sulfated) thyroid hormone transporters in the solute carrier 22 family

Objective: Thyroid hormone (TH) transport represents a critical first step in governing intracellular TH regulation. It is still unknown whether the full repertoire of TH transporters has been identified. Members of the solute carrier (SLC) 22 family have substrates in common with the known TH transporters of the organic anion-transporting peptide family. Therefore, we screened the SLC22 family for TH transporters Methods: Uptake of 1 nM of iodothyronines or sulfated iodothyronines in COS1 cells expressing SLC22 proteins was performed. Results: We first tested 25 mouse (m) SLC22 proteins for TH uptake and fo und that the majority of the organic anion transporter (OAT) clade were capable of 3,3’,5-triiodothyronine and/or thyroxine (T4) transport. Based on phylogenetic tree analysis of the mouse and human (h) SLC22 family, we selected eight hSLC22s that grouped with the newly identified mouse TH transporters. Of thes e, four tested positive for uptake of one or more substrates, particularly hSLC22A11 showed robust (3-fold over control) uptake of T4. Uptake of sulfated iodothyronines was strongly (up to 17-fold) induced by some SLC22s, most notably SLC22A8, hSLC22A9, mSLC22A27 and mSLC22A29. Finally, the zebrafish orthologues of SLC22A6/8 drOat x and drSlc22a6l also transported almost all (sulfated) iodothyronines tested. The OAT inhibitors lesinurad and probenecid inhibited most SLC22 proteins. Conclusions: Our results demonstrated that members of the OAT clade of the SLC22 family constitute a novel, evolutionary conserved group of transporters for (sulfated) iodothyronines. Future studies should reveal the relevance of these transporters in TH homeostasis and physiology

Phosphorylation and Activation of the Plasma Membrane Na+/H+ Exchanger (NHE1) during Osmotic Cell Shrinkage

The Na+/H+ Exchanger isoform 1 (NHE1) is a highly versatile, broadly distributed and precisely controlled transport protein that mediates volume and pH regulation in most cell types. NHE1 phosphorylation contributes to Na+/H+ exchange activity in response to phorbol esters, growth factors or protein phosphatase inhibitors, but has not been observed during activation by osmotic cell shrinkage (OCS). We examined the role of NHE1 phosphorylation during activation by OCS, using an ideal model system, the Amphiuma tridactylum red blood cell (atRBC). Na+/H+ exchange in atRBCs is mediated by an NHE1 homolog (atNHE1) that is 79% identical to human NHE1 at the amino acid level. NHE1 activity in atRBCs is exceptionally robust in that transport activity can increase more than 2 orders of magnitude from rest to full activation. Michaelis-Menten transport kinetics indicates that either OCS or treatment with the phosphatase inhibitor calyculin-A (CLA) increase Na+ transport capacity without affecting transport affinity (Km = 44 mM) in atRBCs. CLA and OCS act non-additively to activate atNHE1, indicating convergent, phosphorylation-dependent signaling in atNHE1 activation. In situ 32P labeling and immunoprecipitation demonstrates that the net phosphorylation of atNHE1 is increased 4-fold during OCS coinciding with a more than 2-order increase in Na+ transport activity. This is the first reported evidence of increased NHE1 phosphorylation during OCS in any vertebrate cell type. Finally, liquid chromatography and mass spectrometry (LC-MS/MS) analysis of atNHE1 immunoprecipitated from atRBC membranes reveals 9 phosphorylated serine/threonine residues, suggesting that activation of atNHE1 involves multiple phosphorylation and/or dephosphorylation events