High but stable incidence of adult-onset asthma in northern Sweden over the last decades

Background The prevalence of asthma has increased both among children and adults during the latter half of the 20th century. The prevalence among adults is affected by the incidence of asthma not only in childhood but also in adulthood. Time trends in asthma incidence have been poorly studied. Aims The aim of this study was to review the incidence of adult-onset asthma from 1996 to 2006 and 2006 to 2016 and compare the risk factor patterns. Methods In the Obstructive Lung Disease in Northern Sweden (OLIN) studies, two randomly selected population-based samples in the 20-69-year age group participated in postal questionnaire surveys about asthma in 1996 (n=7104, 85%) and 2006 (n=6165, 77%). A 10-year follow-up of the two cohorts with the same validated questionnaire was performed, and 5709 and 4552 responded, respectively. Different definitions of population at risk were used in the calculations of asthma incidence. The protocol followed a study performed between 1986 and 1996 in the same area. Results The crude incidence rate of physician-diagnosed asthma was 4.4 per 1000 person-years (men 3.8, women 5.5) from 1996 to 2006, and 4.8 per 1000 person-years (men 3.7, women 6.2) from 2006 to 2016. When correcting for possible under-diagnosis at study entry, the incidence rate was 2.4 per 1000 personyears from 1996 to 2006 and 2.6 per 1000 person-years from 2006 to 2016. The incidence rates were similar across age groups. Allergic rhino-conjunctivitis was the main risk factor for incident asthma in both observation periods (risk ratio 2.4-2.6). Conclusions The incidence of adult-onset asthma has been stable over the last two decades and has remained at a similar level since the 1980s. The high incidence contributes to the increase in asthma prevalence.Peer reviewe

Defining orellanine as treatment of advanced renal cell carcinoma

Renal cancer causes over 100,000 annual deaths worldwide, and the incidence is increasing. Clear cell renal cell carcinomas (CCRCC), constituting 75% of renal cancer, are known for their high metastatic frequency and resistance to conventional therapies. Metastases are encountered in over half of patients with renal cancer, drastically reducing their life expectancy. Even with new specifically directed molecularly targeted therapies, the median survival of metastasizing CCRCC is less than one year. Orellanine is a nephrotoxin found in fungi, and sometimes ingested accidentally. The ingestion of the fungi leads to renal failure and disruption of the proximal tubular cells. Interestingly, CCRCC originate from this cell type. Our hypothesis is that since proximal tubular cells in the kidney selectively take up orellanine, cancer cells in metastases of the same origin would also do so. This may give rise to a potentially curative therapy against metastasizing CCRCC. The aim of the thesis is to 1) Determine the efficacy of orellanine as a targeted therapy against clear cell renal cell carcinoma in vitro and in vivo 2) Establish a robust technique for detection of orellanine in plasma 3) Evaluate the long-term effects in patients after accidental intake of mushrooms containing orellanine. We could demonstrate that orellanine induces dose-dependent cell death in a number of CCRCC cells while cells from other areas of the body remained unharmed. When we treated human CCRCC xenografts in nude rats with orellanine, the tumor cell mass was significantly reduced within a few days, featuring large apoptotic and necrotic areas. We could also detect orellanine with our newly developed analysis method in minute concentrations. This is necessary for monitoring orellanine concentrations in the body in a possible future clinical trial. The specificity for renal cells was evident in our study of the long-term outcome after accidental intake of orellanine-containing mushrooms. In these patients, we could not detect any difference in mortality or morbidity compared to age- and sex-matched controls. In conclusion, this thesis shows that orellanine is indeed highly toxic to CCRCC cells both in vitro and in vivo. Orellanine seems to be highly kidney-specific with no long-term effects other than renal failure, which can be well dealt with using dialysis or renal transplantation. Orellanine thus has potential to become a new potentially curative treatment of metastatic CCRCC

RapidHIT for the purpose of stain analyses - An interrupted implementation

Rapid DNA instruments have in recent years been developed, enabling analysis of forensic samples with a minimum of human intervention. Initially intended for fast handling of reference samples, such as samples from suspects in booking suites, attention shifted to include crime scene samples. The aim of this study was to determine whether or not the RapidHIT System (IntegenX) is fit for crime scene samples. The first runs gave very poor results, which was found to be due to an incorrect firmware setting leading to no or just minute amounts of amplicons being injected for electrophoresis. After solving this problem, 28 full runs (seven samples each) applying NGM SElect Express were performed comprising various amounts of blood on cotton swabs. Six of the runs failed completely, four due to cartridge leakage and in two runs the PCR mix was not injected. For 155 samples with 1-5. μL blood (volumes for which complete DNA profiles are expected), 119 samples (77%) gave complete DNA profiles. Among the most serious failures were incorrect allele calling and leakage of DNA extract or PCR product. Other general issues were failure to export results, anode motor breakdown and broken capillary array. Due to the encountered problems with software, hardware and cartridges, together with the low success rate, it was decided not to continue towards implementation of the RapidHIT System in casework

Biological and Immunological Relations among Human Parvovirus B19 Genotypes 1 to 3▿

The human parvovirus B19 is now divided into three genotypes: type 1 (prototype), type 2 (A6- and LaLi-like), and type 3 (V9-like). In overall DNA sequence, the three virus types differ by ∼10%. The most striking DNA dissimilarity, of >20%, is observed within the p6 promoter region. Because of the scarcity of data on the biological activities and pathogenetic potentials of virus types 2 and 3, we examined the functional characteristics of these virus types. We found the activities of the three p6 promoters to be of equal strength and to be most active in B19-permissive cells. Virus type 2 capsid protein VP2, alone or together with VP1, was expressed with the baculovirus system and was shown to assemble into icosahedral parvovirus-like particles, which were reactive in the hemagglutination assay. Furthermore, sera containing DNA of any of the three B19 types were shown to hemagglutinate. The infectivities of these sera were examined in two B19-permissive cell lines. Reverse transcription-PCR revealed synthesis of spliced B19 mRNAs, and immunofluorescence verified the production of NS and VP proteins in the infected cells. All three genotypes showed similar functional characteristics in all experiments performed, showing that the three virus types indeed belong to the same species, i.e., human parvovirus B19. Additionally, the antibody activity in sera from B19 type 1- or type 2-infected subjects (long-term immunity) was examined with homo- and heterologous virus-like particles. Cross-reactivity of 100% was observed, indicating that the two B19 genotypes comprise a single serotype

Is there still a social gradient in respiratory symptoms? A population-based Nordic EpiLung-study

Background: Respiratory symptoms are a common public health issue that can partly be attributed to preventable risk factors, such as tobacco smoking and occupational exposure, which are more common in individuals with lower socioeconomic status. Objective: Our aim was to evaluate the social gradient in respiratory symptoms in Nordic countries. Methods: This study included participants aged 30–65 years from five cross-sectional population-based questionnaire surveys in 2016 in Finland and Sweden (N = 25,423) and in 2017–2019 in Norway (N = 27,107). Occupational skill levels 1 and 2 (occupations requiring compulsory education) were combined and compared to skill levels 3 and 4 (occupations requiring upper secondary and tertiary education). Meta-analysis was conducted to obtain pooled age- and sex adjusted odds ratios (aORs) of associations between occupational skill and the respiratory symptoms including recurrent wheeze, dyspnoea, and productive cough. Results: In the meta-analysis, recurrent wheeze, dyspnoea, and productive cough showed a social gradient. The participants with occupational skill 1 and 2 had higher risk for recurrent wheeze (aOR 1.78, 95% CI 1.34–2.22) and dyspnoea (aOR 1.59, 95% CI 1.29–1.90) compared to occupational skill 3 and 4 in Sweden and Finland. Similarly increased risk was observed for combined assessment of dyspnoea and wheeze (aOR 1.05, 95% CI 1.03–1.07) in Norway. In a meta-analysis including all three countries, the aOR for productive cough was 1.31 95% CI 1.07–1.56. Conclusions: Occupations with lower, compared to higher, skill levels were associated with an increased risk of recurrent wheeze, dyspnoea, and productive cough.Peer reviewe

Interaction of smoking and social status on the risk of respiratory outcomes in a Swedish adult population : A Nordic Epilung study

Background: Evidence abounds on the independent roles of social class and smoking in relation to obstructive airway diseases, but data are sparse on the impact of their interaction. We evaluated whether and to what extent social class and smoking interact in relation to risk of respiratory diseases in adults. Methods: Data from the population-based studies, West Sweden Asthma Study (WSAS, n = 23,753) and Obstructive Lung Disease in Northern Sweden studies (OLIN, n = 6519), were used, constituting randomly selected adults aged 20–75 years. Bayesian network analysis was used to estimate the probability for the interaction between smoking and socioeconomic status in relation to respiratory outcomes. Results: Occupational and educational SES modified the association between smoking and the probability of allergic and non-allergic asthma. Former smokers who were at intermediate non manual employees and manual workers in service had higher probability of allergic asthma compared to professionals and executives. Furthermore, former smokers with primary education had higher probability of non-allergic asthma than those with secondary and tertiary education. Similarly, former smokers among professionals and executives had higher probability of non-allergic asthma than manual and home workers and primary educated. Likewise, allergic asthma due to former smoking was higher among highly educated compared to low educated. Conclusions: Beyond their independent roles, socioeconomic status and smoking interact in defining the risk of respiratory diseases. Clearer understanding of this interaction can help to identify population subgroups at most need of public health interventions

Saturn's Atmosphere in Northern Summer Revealed by JWST/MIRI

International audienceSaturn's northern summertime hemisphere was mapped by JWST/Mid-Infrared Instrument (4.9-27.9 µm) in November 2022, tracing the seasonal evolution of temperatures, aerosols, and chemical species in the 5 years since the end of the Cassini mission. The spectral region between reflected sunlight and thermal emission (5.1-6.8 µm) is mapped for the first time, enabling retrievals of phosphine, ammonia, and water, alongside a system of two aerosol layers (an upper tropospheric haze p < 0.3 bars, and a deeper cloud layer at 1-2 bars). Ammonia displays substantial equatorial enrichment, suggesting similar dynamical processes to those found in Jupiter's equatorial zone. Saturn's North Polar Stratospheric Vortex has warmed since 2017, entrained by westward winds at p < 10 mbar, and exhibits localized enhancements in several hydrocarbons. The strongest latitudinal temperature gradients are co-located with the peaks of the zonal winds, implying wind decay with altitude. Reflectivity contrasts at 5-6 µm compare favorably with albedo contrasts observed by Hubble, and several discrete vortices are observed. A warm equatorial stratospheric band in 2022 is not consistent with a 15-year repeatability for the equatorial oscillation. A stacked system of windshear zones dominates Saturn's equatorial stratosphere, and implies a westward equatorial jet near 1-5 mbar at this epoch. Lower stratospheric temperatures, and local minima in the distributions of several hydrocarbons, imply low-latitude upwelling and a reversal of Saturn's interhemispheric circulation since equinox. Latitudinal distributions of stratospheric ethylene, benzene, methyl, and carbon dioxide are presented for the first time, and we report the first detection of propane bands in the 8-11 µm region

Orellanine specifically targets renal clear cell carcinoma

Renal cell carcinoma (RCC), arising from the proximal tubule in the kidney, accounts for approximately 85% of kidney cancers and causes over 140,000 annual deaths worldwide. In the last decade, several new therapies have been identified for treatment of metastatic RCC. Although these therapies increase survival time compared to standard care, none of them has curative properties. The nephrotoxin orellanine specifically targets proximal tubular epithelial cells, leaving other organs unaffected. We therefore hypothesized that the selective toxicity of orellanine extends to clear cell RCC (ccRCC) cells since they emanate from proximal tubular cells. Orellanine would thus target both primary and metastatic ccRCC in vitro and in vivo. We found that orellanine induces dose-dependent cell death in proximal tubular cells and in all ccRCC cells tested, both primary and cell lines, with no toxicity detected in control cells. The toxic action of orellanine involve decreased protein synthesis, disrupted cell metabolism and induction of apoptosis. In nude rats carrying human ccRCC xenografts, brief orellanine treatment eliminated more than 90% of viable tumor mass compared to control rats. This identifies orellanine as a potential treatment concept for ccRCC patients on dialysis, due to its unique selective toxicity towards ccRCC