Validation of Self-testing as a Method to Estimate the Prevalence of Nickel Allergy

The aim of this study was to investigate the validity of self-patch testing for nickel allergy, in order to determine a cost-effective method for surveillance of the prevalence of nickel allergy. Population-based study including patch testing is the most reliable method to study the prevalence of allergy, but it is expensive and has logistical problems. A total of 191 dermatology patients referred to patch testing were provided with a self-test package with written instructions. The self-test was applied on the arm by the patient, on the same day that the regular patch test was applied on the back. The patient evaluated the self-test before patch test reading at the clinic. Patch test at the dermatology clinic detected 46/191 (24%) nickel-positive individuals. The sensitivity of the self-test was 72% (95% confidence interval (Cl) 57-84), the specificity 91% (95% Cl 85-95), and the proportion of agreement 86% (95% CI 81-91). Thus, in the population studied, the validity of self-testing for nickel allergy was adequate

The role of recurrent disturbances for ecosystem multifunctionality

Ecosystem functioning is threatened by an increasing number of anthropogenic stressors, creating a legacy of disturbance that undermines ecosystem resilience. However, few empirical studies have assessed to what extent an ecosystem can tolerate repeated disturbances and sustain its multiple functions. By inducing increasingly recurring hypoxic disturbances to a sedimentary ecosystem, we show that the majority of individual ecosystem functions experience gradual degradation patterns in response to repetitive pulse disturbances. The degradation in overall ecosystem functioning was, however, evident at an earlier stage than for single ecosystem functions and was induced after a short pulse of hypoxia (i.e., three days), which likely reduced ecosystem resistance to further hypoxic perturbations. The increasing number of repeated pulse disturbances gradually moved the system closer to a press response. In addition to the disturbance regime, the changes in benthic trait composition as well as habitat heterogeneity were important for explaining the variability in overall ecosystem functioning. Our results suggest that disturbance-induced responses across multiple ecosystem functions can serve as a warning signal for losses of the adaptive capacity of an ecosystem, and might at an early stage provide information to managers and policy makers when remediation efforts should be initiated.Peer reviewe

Changes in macrofaunal biological traits across estuarine gradients : implications for the coastal nutrient filter

Benthic macrofaunal communities have a profound impact on organic matter turnover and nutrient cycling in marine sediments. Their activities are of particular importance in the coastal filter, where nutrients and organic matter from land are transformed and/or retained before reaching the open sea. The benthic fauna modify the coastal filter directly (through consumption, respiration, excretion and biomass production) and indirectly (through bioturbation). It is hard to experimentally quantify faunal contribution to the coastal filter over large spatial and temporal scales that encompass significant environmental and biological heterogeneity. However, estimates can be obtained with biological trait analyses. By using benthic biological traits, we explored how the potential contribution of macrofaunal communities to the coastal filter differ between inner and outer sites in an extensive archipelago area and examine the generality of the observed pattern across contrasting coastal areas of the entire Baltic Sea. Estimates of benthic bioturbation, longevity and size (i.e. ‘stability’) and total energy and nutrient contents differed between coastal areas and inner versus outer sites. Benthic traits indicative of an enhanced nutrient turnover but a decreased capacity for temporal nutrient retention dominated inner sites, while outer sites were often dominated by larger individuals, exhibiting traits that are likely to enhance nutrient uptake and retention. The overarching similarities in benthic trait expression between more eutrophied inner vs. less affected outer coastal sites across the Baltic Sea suggest that benthic communities might contribute in a similar manner to nutrient recycling and retention in the coastal filter over large geographical scales.peerReviewe

Asymmetric Inheritance of Aggregated Proteins and Age Reset in Yeast Are Regulated by Vac17-Dependent Vacuolar Functions

SummaryAge can be reset during mitosis in both yeast and stem cells to generate a young daughter cell from an aged and deteriorated one. This phenomenon requires asymmetry-generating genes (AGGs) that govern the asymmetrical inheritance of aggregated proteins. Using a genome-wide imaging screen to identify AGGs in Saccharomyces cerevisiae, we discovered a previously unknown role for endocytosis, vacuole fusion, and the myosin-dependent adaptor protein Vac17 in asymmetrical inheritance of misfolded proteins. Overproduction of Vac17 increases deposition of aggregates into cytoprotective vacuole-associated sites, counteracts age-related breakdown of endocytosis and vacuole integrity, and extends replicative lifespan. The link between damage asymmetry and vesicle trafficking can be explained by a direct interaction between aggregates and vesicles. We also show that the protein disaggregase Hsp104 interacts physically with endocytic vesicle-associated proteins, such as the dynamin-like protein, Vps1, which was also shown to be required for Vac17-dependent sequestration of protein aggregates. These data demonstrate that two physiognomies of aging—reduced endocytosis and protein aggregation—are interconnected and regulated by Vac17

Genotype-stratified treatment for monogenic insulin resistance: a systematic review

This is the final version. Available from Nature Research via the DOI in this record. Data availability: All data used in this review is available from publicly available and herein referenced sources. A list of included studies is provided in Supplementary Data 1. All data generated or analyzed during this study are included in this published article and its supplementary information files. Source data for the figures are available as Supplementary Data 2.BACKGROUND: Monogenic insulin resistance (IR) includes lipodystrophy and disorders of insulin signalling. We sought to assess the effects of interventions in monogenic IR, stratified by genetic aetiology. METHODS: Systematic review using PubMed, MEDLINE and Embase (1 January 1987 to 23 June 2021). Studies reporting individual-level effects of pharmacologic and/or surgical interventions in monogenic IR were eligible. Individual data were extracted and duplicates were removed. Outcomes were analysed for each gene and intervention, and in aggregate for partial, generalised and all lipodystrophy. RESULTS: 10 non-randomised experimental studies, 8 case series, and 23 case reports meet inclusion criteria, all rated as having moderate or serious risk of bias. Metreleptin use is associated with the lowering of triglycerides and haemoglobin A1c (HbA1c) in all lipodystrophy (n = 111), partial (n = 71) and generalised lipodystrophy (n = 41), and in LMNA, PPARG, AGPAT2 or BSCL2 subgroups (n = 72,13,21 and 21 respectively). Body Mass Index (BMI) is lowered in partial and generalised lipodystrophy, and in LMNA or BSCL2, but not PPARG or AGPAT2 subgroups. Thiazolidinediones are associated with improved HbA1c and triglycerides in all lipodystrophy (n = 13), improved HbA1c in PPARG (n = 5), and improved triglycerides in LMNA (n = 7). In INSR-related IR, rhIGF-1, alone or with IGFBP3, is associated with improved HbA1c (n = 17). The small size or absence of other genotype-treatment combinations preclude firm conclusions. CONCLUSIONS: The evidence guiding genotype-specific treatment of monogenic IR is of low to very low quality. Metreleptin and Thiazolidinediones appear to improve metabolic markers in lipodystrophy, and rhIGF-1 appears to lower HbA1c in INSR-related IR. For other interventions, there is insufficient evidence to assess efficacy and risks in aggregated lipodystrophy or genetic subgroups.Wellcome TrustWellcome Trus

Nickel allergy and hand eczema : epidemiological aspects

Nickel allergy is the most prevalent contact allergy and has been discussed as a possible riskfactor for hand eczema. However, hand eczema is one of the most frequently occurring skindiseases and has multifactorial origin. The aim of this thesis was to study the association between nickel allergy and hand eczema in the general population. There are only a fewpopulation-based studies previously published, that include patch testing. In addition, this thesis aimed to evaluate methods to follow the prevalence of nickel allergy.The study cohort consisted of 908 women who had been patch tested for the occurrence of nickel allergy as schoolgirls. Twenty years later, they were invited to participate in a follow-up questionnaire study. The response rate was 81%. In total, 17.6% of respondents reported handeczema after the age of 15 years and there was no statistically significant difference in the occurrence of hand eczema between those who were nickel-positive and those who were nickel negativeas schoolgirls. To further investigate possible links, another study was performed,which included a second questionnaire, a clinical investigation and patch testing. All schoolgirls from the baseline study who were still living in the area as adults were invited to participate and the participation rate was 77%. Patch test showed 30.1% nickel-positive individuals.When all participants were included in the analysis, there was no statistically significant difference between nickel-positive and nickel-negative women regarding occurrence of hand eczema. The most important risk factor for hand eczema was childhood eczema. Adjusted prevalence proportion ratio (PPR) for hand eczema after age 15 in relation to nickel patch testresults was 1.03 (95% CI 0.71--1.50) and in relation to childhood eczema 3.68 (95% CI 2.45--5.54). When women with and without history of childhood eczema were analyzed separately, the hand eczema risk was doubled in nickel-positive women without history of childhood eczema. In conclusion, the risk of hand eczema in nickel-positive women may previously havebeen overestimated. Next, the validity of self-reported nickel allergy was investigated. In the established cohort; two questions regarding nickel allergy were compared with patch test results. The validity of self-reported nickel allergy was low, and the questions regarding nickel allergy overestimated the true prevalence of nickel allergy. The positive predictive values were 59% and 60%. Another method for estimating the prevalence of nickel allergy, namely self-patch testing, was validated in the last study. In total, 191 patients from three different dermatology departments participated. The validity of self-testing for nickel allergy was adequate, with sensitivity 72%and proportion of agreement 86%.Nickelallergi är vanligt förekommande. Prevalensen i Skandinavien är 15--25% hos kvinnor och cirka 3% hos män. Sambandet mellan nickelallergi och uppkomst av handeksem har tidigare diskuterats och i vissa studier anges att 30--45% av alla individer med nickelallergi får handeksem. Det finns dock endast ett fåtal publicerade studier där personer ur normalbefolkningen har lapptestats för nickel. Handeksem ärvanligt och har ofta flera olika kombinerade orsaker. Det övergripande syftet med avhandlingen var att studera nickelallergins betydelse för uppkomst av handeksem. Detfinns ett intresse av att följa förekomsten av nickelallergi över tid, speciellt sedan det i början av 2000-talet infördes ett EU-direktiv som begränsar nickelinnehåll i klockor,smycken, metallknappar etc. Ytterligare ett syfte med avhandlingen var att utvärderaepidemiologiska metoder för att följa förekomsten av nickelallergi.Den första studien var en uppföljningsstudie av 908 flickor ur normalbefolkningen,vilka i skolåldern lapptestats med nickel. Tjugo år senare skickades en enkät till dessa kvinnor, svarsfrekvensen var hög (81%). Förekomsten av självrapporterat handeksemefter 15 års ålder var 17.6%. Det förelåg ingen signifikant skillnad i förekomst avhandeksem mellan de kvinnor som var nickelallergiska som barn jämfört med dem som inte var nickelallergiska. År 2006 utfördes ytterligare en studie, som inkluderade de kvinnor som fortfarande bodde i Örebro län. Studien omfattade en klinisk undersökning av händerna samt ett lapptest. 30% av kvinnorna var positiva för nickel.Det förelåg ingen signifikant skillnad i förekomst av handeksem mellan de som var positiva för nickel och de som var negativa. Vid separat analys av de kvinnor som angav tidigare barneksem jämfört med dem som aldrig hade haft barneksem visade det sig att risken för handeksem var dubbelt så stor hos nickelallergiker i den gruppen som aldrig hade haft barneksem. Båda studierna visade att barneksem var den största riskfaktorn för att få handeksem som vuxen, med en 3-4 gånger ökad risk. Den tredje studien var en validering av självrapporterad nickelallergi. Överensstämmelsen var låg mellan enkätfrågor gällande nickelallergi och lapptestverifierad nickelallergi. Av dem som själva bedömde sig vara nickelallergiska var endast 59% positiva enligt lapptest. För att följa förekomsten av nickelallergi i befolkningen behövs därför andra metoder. I den fjärde studien utvärderades ett självtest för nickelallergi. 191 patienter från tre olika hudkliniker i Sverige deltog i studien. Validiteten för metoden självtest var tillfredsställande, sensitiviteten var 72%och graden av överensstämmelse var 86%

Incidence Rate of Hand Eczema in Different Occupations : A Systematic Review and Meta-analysis

Hand eczema is a chronic disease that results in economic and psychosocial burdens. The aim of this study was to systematically review and assess the magnitude of the association between exposure related to occupations and the incidence rate of hand eczema. A systematic search in PubMed, EMBASE, CINAHL and Cochrane databases, from inception to September 2017, of full-text observational studies reporting incident cases of hand eczema during employment, and a supplementary search in PubMed to September 2020, were conducted. Among 2,417 screened abstracts, 15 studies fulfilled the inclusion criteria. Incidence rates were reported per 100 person-years. Based on the Newcastle-Ottawa Scale, 9 studies were good quality, 2 fair quality, and 4 poor quality. Hairdressers had a high incidence of hand eczema of 21.4 (95% confidence interval [CI] 15.3–27.4), as did nurses, 16.9 (95% CI 11.2–22.7), and metal workers, 12.4 (95% CI 3.5–21.3). Hairdressers were predominantly women, and metal worker were predominantly men. Office occupations had an incidence rate of hand eczema of 4.9 (95% CI 1.2–9.6). The high risk of hand eczema for hairdressers, nurses, and metal workers, should be considered by healthcare policymakers. Even occupations with low irritant profile, such as office workers, were at risk of developing hand eczema, and more occupations should be investigated regarding the related risk of developing hand eczema

TOF-SIMS analysis of exhaled particles from patients with asthma and healthy controls.

Particles in exhaled air (PEx) may reflect the composition of respiratory tract lining fluid (RTLF); thus, there is a need to assess their potential as sources of biomarkers for respiratory diseases. In the present study, we compared PEx from patients with asthma and controls using time-of-flight-secondary ion mass spectrometry (TOF-SIMS) and multivariate analysis. Particles were collected using an instrument developed in-house. 15 nonsmoking subjects with physician-diagnosed asthma and 11 nonsmoking healthy controls performed 10 consecutive forced exhalations into the instrument. Particle concentrations were recorded and samples of particles collected on silicon plates were analysed by TOF-SIMS. Subjects with asthma exhaled significantly lower numbers of particles than controls (p=0.03) and the ratio of unsaturated to saturated phospholipids was significantly lower in samples from subjects with asthma (0.25 versus 0.35; p=0.036). Orthogonal partial least squares-discriminant analysis models showed good separation between both positive and negative spectra. Molecular ions from phosphatidylcholine and phosphatidylglycerol, and protein fragments were found to discriminate the groups. We conclude that analysis of PEx is a promising method to examine the composition of RTLF. In the present explorative study, we could discriminate between subjects with asthma and healthy controls based on TOF-SIMS spectra from PEx

TOF-SIMS analysis of exhaled particles from patients with asthma and healthy controls.

Particles in exhaled air (PEx) may reflect the composition of respiratory tract lining fluid (RTLF); thus, there is a need to assess their potential as sources of biomarkers for respiratory diseases. In the present study, we compared PEx from patients with asthma and controls using time-of-flight-secondary ion mass spectrometry (TOF-SIMS) and multivariate analysis. Particles were collected using an instrument developed in-house. 15 nonsmoking subjects with physician-diagnosed asthma and 11 nonsmoking healthy controls performed 10 consecutive forced exhalations into the instrument. Particle concentrations were recorded and samples of particles collected on silicon plates were analysed by TOF-SIMS. Subjects with asthma exhaled significantly lower numbers of particles than controls (p=0.03) and the ratio of unsaturated to saturated phospholipids was significantly lower in samples from subjects with asthma (0.25 versus 0.35; p=0.036). Orthogonal partial least squares-discriminant analysis models showed good separation between both positive and negative spectra. Molecular ions from phosphatidylcholine and phosphatidylglycerol, and protein fragments were found to discriminate the groups. We conclude that analysis of PEx is a promising method to examine the composition of RTLF. In the present explorative study, we could discriminate between subjects with asthma and healthy controls based on TOF-SIMS spectra from PEx