Objective: To identify susceptibility genes in a rat model of rheumatoid arthritis (RA) and to determine whether the corresponding human genes are associated with RA.Methods: Genes influencing oil‐induced arthritis (OIA) were position mapped by comparing the susceptibility of inbred DA rats with that of DA rats carrying alleles derived from the arthritis‐resistant PVG strain in chromosomal fragments overlapping the quantitative trait locus Oia2. Sequencing of gene complementary DNA (cDNA) and analysis of gene messenger RNA (mRNA) expression were performed to attempt to clone a causal gene. Associations with human RA were evaluated by genotyping single‐nucleotide polymorphisms (SNPs) in the corresponding human genes and by analyzing frequencies of alleles and haplotypes in RA patients and age‐, sex‐, and area‐matched healthy control subjects.Results: Congenic DA rats were resistant to OIA when they carried PVG alleles for the antigen‐presenting lectin‐like receptor gene complex (APLEC), which encodes immunoregulatory C‐type lectin–like receptors. Multiple differences in cDNA sequence and mRNA expression precluded cloning of a single causal gene. Five corresponding human APLEC genes were identified and targeted. The SNP rs1133104 in the dendritic cell immunoreceptor gene (DCIR), and a haplotype including that marker and 4 other SNPs in DCIR and its vicinity showed an indication of allelic association with susceptibility to RA in patients who were negative for antibodies to cyclic citrullinated peptide (anti‐CCP), with respective odds ratios of 1.27 (95% confidence interval [95% CI] 1.06–1.52; uncorrected P = 0.0073) and 1.37 (95% CI 1.12–1.67; uncorrected P = 0.0019). Results of permutation testing supported this association of the haplotype with RA.Conclusion: Rat APLEC is associated with susceptibility to polyarthritis, and human APLEC and DCIR may be associated with susceptibility to anti‐CCP–negative RA.

Crowding in dwellings is an important public health issue. We hypothesize that overcrowding may cause indirect health effects by adversely affecting the dwelling itself, for example, by increasing dampness leading to mold. We therefore performed a systematic search and a scoping review on overcrowding leading to dwelling condition characteristics of relevance for health. A literature search was performed using the PubMed and Scopus databases up to 5 March 2021. The search yielded 100 records with relevant information. We found that overcrowding is defined in numerous ways and often address “socially deprived” populations. Six studies report associations of overcrowding with at least one dwelling condition characteristic, namely lead, cadmium, microorganism distribution, dust mite and cockroach allergens in dust, cockroach infestation, peeling paint, and mold. One of the studies reports associations between several characteristics, e.g., association of mold with cleanliness and rodent infestation, and points out the common use of pesticides. Additional characteristics were extracted from the remaining 94 records, without data on statistical associations with overcrowding. Our review suggests that multiple potentially hazardous dwelling condition characteristics often coincide in overcrowded dwellings. The epidemiological attribution of health effects to any characteristic is therefore difficult. Causal relationships are even more difficult to establish, as overcrowding is also associated with a range of social and other circumstances that may affect health. The complexity should be considered by scientists and practitioners dealing with overcrowding in dwellings.

Indoor mold odor is associated with adverse health effects, but the microbial volatiles underlying mold odor are poorly described. Here, chloroanisoles were studied as potential key players, being formed by microbial metabolism of chlorophenols in wood preservatives. Using a three-stage approach, we (i) investigated the occurrence of chloroanisoles in buildings with indoor air quality problems, (ii) estimated their frequency in Sweden, and (iii) evaluated the toxicological risk of observed chloroanisole concentrations. Analyses of 499 building materials revealed several chloroanisole congeners in various types of buildings from the 1950s to 1970s. Evaluation of Swedish records from this time period revealed three coinciding factors, namely an unprecedented nationwide building boom, national regulations promoting wood preservatives instead of moisture prevention, and use of chlorophenols in these preservatives. Chlorophenols were banned in 1978, yet analysis of 457 indoor air samples revealed several chloroanisole congeners, but at median air levels generally below 15 ng/m(3) . Our toxicological evaluation suggests that these concentrations are not detrimental to human health per se, but sufficiently high to cause malodor. Thereby, one may speculate that chloroanisoles in buildings contribute to adverse health effects by evoking odor which, enhanced by belief of the exposure being hazardous, induces stress-related and inflammatory symptoms.

Objective: The antigen‐presenting lectin‐like receptor complex (APLEC) was recently identified as a genetic determinant for arthritis susceptibility. We undertook this study to define mechanisms underlying the impact of APLEC on arthritis, to determine whether sex effects occur, and to determine whether APLEC influences different types of arthritis and phenotypes other than susceptibility.Methods: Arthritis‐susceptible DA rats were compared with sex‐matched congenic rats in which APLEC alleles were substituted with alleles from arthritis‐resistant PVG rats. Six different arthritogenic agents were injected at the base of the tail: Freund's incomplete adjuvant, pristane, squalene, killed mycobacteria, yeast β‐glucan, or rat type II collagen (CII). Arthritis was visually scored, body weight was measured, and anti‐CII IgG and cytokine messenger RNA (mRNA) levels were determined by enzyme‐linked immunosorbent assay and reverse transcription–polymerase chain reaction, respectively.Results: In 5 models of rheumatoid arthritis (RA), congenic rats deviated profoundly from DA rats by having reduced arthritis susceptibility, delayed onset, decreased severity, and/or reduced body weight loss. Paradoxical opposite genetic effects were noted, including a more severe disease course in congenic males in pristane‐induced arthritis and decreased clinical signs in collagen‐induced arthritis despite increased autoantibody levels. Interestingly, the anti‐CII IgG isotype profile was skewed in congenic rats, and markedly reduced lymph node mRNA levels for interleukin‐17 suggested that the cytokine profile of autoreactive T helper cells was also skewed in a less pathogenic direction.Conclusion: Rat APLEC regulates autoimmunity and multiple phenotypes in several types of arthritis. However, delineating the genetic impact may require stratification for sex or mode of arthritis induction. This pathogenetic complexity should be considered when evaluating APLEC in inflammatory and autoimmune diseases, including RA.

Aim: To explore how overcrowding affects children’s health, environment and schooling. Methods: A qualitative study was conducted with individual interviews among 20 participants with occupational experience from overcrowded Stockholm areas but diverse in professions, locations and employers. The interviews were recorded, transcribed and analysed with Systematic Text Condensation. Results: Almost all participants expressed that overcrowding has a negative impact on children’s health, environment and schooling – based on perceptions of precarious and different living conditions for children in overcrowded areas, for example, substandard homes, vulnerability, stress, exclusion, limited resources, lack of learning opportunities, gender differences, confinement, shame, insecurity, conflicts, risk of criminality, and bodily impact, both physical and psychological. Conclusions: Our qualitative evidence suggest that overcrowding has a negative impact on children’s health, environment and schooling.