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AIMS: To examine whether asthma induced by exposure to aluminium potroom emissions (potroom asthma) is associated with inflammatory changes in the airways. METHODS: Bronchial biopsy specimens from 20 asthmatic workers (8 non-smokers and 12 smokers), 15 healthy workers (8 non-smokers and 7 smokers), and 10 non-exposed controls (all non-smokers) were analysed. Immunohistofluorescent staining was performed to identify mucosal total leucocytes (CD45+ leucocytes), neutrophils, and mast cells. RESULTS: Median RBM thickness was significantly increased in both asthmatic workers (8.2 microm) and healthy workers (7.4 microm) compared to non-exposed controls (6.7 microm). Non-smoking asthmatic workers had significantly increased median density of lamina propria CD45+ leucocytes (1519 cells/mm2 v 660 and 887 cells/mm2) and eosinophils (27 cells/mm2 v 10 and 3 cells/mm2) and significantly increased concentrations of exhaled NO (18.1 ppb v 6.5 and 5.1 ppb) compared to non-smoking healthy workers and non-exposed controls. Leucocyte counts and exhaled NO concentrations varied with smoking habits and fewer leucocytes were observed in asthmatic smokers than in non-smokers Asthmatic smokers had significantly increased numbers of eosinophils in lamina propria compared to non-exposed controls (10 v 3 cells/mm2). Both eosinophilic and non-eosinophilic phenotypes of asthma were recognised in the potroom workers and signs of airway inflammation were also observed in healthy workers. CONCLUSIONS: Airway inflammation is a central feature of potroom asthma and exposure to potroom emissions induces pathological alterations similar to those described in other types of asthma. Cigarette smoking seems to affect the underlying mechanisms involved in asthma, as the cellular composition of airway mucosa appears different in asthmatic smokers and non-smokers. [ABSTRACT FROM AUTHOR]

Microbial formation and oxidation of volatile alkanes in anoxic environments significantly impacts biogeochemical cycles on Earth. The discovery of archaea oxidizing volatile alkanes via deeply branching methyl-coenzyme M reductase variants, dubbed alkyl-CoM reductases (ACR), prompted the hypothesis of archaea-catalysed alkane formation in nature (alkanogenesis). A combination of metabolic modelling, anaerobic physiology assays, and isotope labeling of Candidatus Syntrophoarchaeum archaea catalyzing the anaerobic oxidation of butane (AOB) show a back flux of CO 2 to butane, demonstrating reversibility of the entire AOB pathway. Back fluxes correlate with thermodynamics and kinetics of the archaeal catabolic system. AOB reversibility supports a biological formation of butane, and generally of higher volatile alkanes, helping to explain the presence of isotopically light alkanes and deeply branching ACR genes in sedimentary basins isolated from gas reservoirs., (© 2024. The Author(s).)

How species thrive in a wide range of environments is a major focus of evolutionary biology. For many species, limited genetic diversity or gene flow among habitats means that phenotypic plasticity must play an important role in their capacity to tolerate environmental heterogeneity and to colonize new habitats. However, we have a limited understanding of the molecular components that govern plasticity in ecologically relevant phenotypes. We examined this hypothesis in a spider species (Stegodyphus dumicola) with extremely low species-wide genetic diversity that nevertheless occupies a broad range of thermal environments. We determined phenotypic responses to temperature stress in individuals from four climatic zones using common garden acclimation experiments to disentangle phenotypic plasticity from genetic adaptations. Simultaneously, we created data sets on multiple molecular modalities: the genome, the transcriptome, the methylome, the metabolome, and the bacterial microbiome to determine associations with phenotypic responses. Analyses of phenotypic and molecular associations reveal that acclimation responses in the transcriptome and metabolome correlate with patterns of phenotypic plasticity in temperature tolerance. Surprisingly, genes whose expression seemed to be involved in plasticity in temperature tolerance were generally highly methylated contradicting the idea that DNA methylation stabilizes gene expression. This suggests that the function of DNA methylation in invertebrates varies not only among species but also among genes. The bacterial microbiome was stable across the acclimation period; combined with our previous demonstrations that the microbiome is temporally stable in wild populations, this is convincing evidence that the microbiome does not facilitate plasticity in temperature tolerance. Our results suggest that population-specific variation in temperature tolerance among acclimation temperatures appears to result from the evolution of plasticity in mainly gene expression., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Background: Crystalline silica (CS) exposure can cause serious lung disease in humans, but mechanisms of pulmonary toxicity have not been completely elucidated., Aims: To assess pro-inflammatory and anti-inflammatory biomarkers and biomarkers related to the development of chronic obstructive pulmonary disease and fibrosis in serum of rock drillers exposed to CS., Methods: Rock drillers (N = 123) exposed to CS and non-specified particulate matter (PM) were compared to 48 referents without current or past exposure to PM in a cross-sectional study., Results: The rock drillers had been exposed to CS for 10.7 years on average. Geometric mean (GM) current exposure was estimated to 36 µg/m 3 . Their GM concentration of matrix metalloproteinase 12 (MMP-12) was significantly higher (16 vs. 13 ng/L; p = 0.04), while interleukin (IL) 6 and IL-8 were significantly lower compared to the referents. Also pentraxin 3 was significantly lower (3558 vs. 4592 ng/L; p = 0.01) in the rock drillers. A dose-response relationship was observed between cumulative exposure to CS and MMP-12, the highest exposed subgroup having significantly higher MMP-12 concentrations than the referents., Conclusion: Exposure to CS may increase circulating MMP-12 concentrations in a dose-response related fashion. The results may also suggest a down-regulation of pro-inflammatory pathways., (© 2024. The Author(s).)

Bacterial biofilms have a complex and heterogeneous three-dimensional architecture that is characterized by chemically and structurally distinct microenvironments. Confocal microscopy-based pH ratiometry and fluorescence lectin-binding analysis (FLBA) are well-established methods to characterize pH developments and the carbohydrate matrix architecture of biofilms at the microscale. Here, we developed a combined analysis, pH-FLBA, to concomitantly map biofilm pH and the distribution of matrix carbohydrates in bacterial biofilms while preserving the biofilm microarchitecture. As a proof of principle, the relationship between pH and the presence of galactose- and fucose-containing matrix components was investigated in dental biofilms grown with and without sucrose. The pH response to a sucrose challenge was monitored in different areas at the biofilm base using the ratiometric pH-sensitive dye C-SNARF-4. Thereafter, the fucose- and galactose-specific fluorescently labeled lectins Aleuria aurantia lectin (AAL) and Morus nigra agglutinin G (MNA-G) were used to visualize carbohydrate matrix components in the same biofilm areas and their immediate surroundings. Sucrose during growth significantly decreased biofilm pH ( P < 0.05) and increased the amounts of both MNA-G- and AAL-targeted matrix carbohydrates ( P < 0.05). Moreover, it modulated the biofilm composition towards a less diverse community dominated by streptococci, as determined by 16S rRNA gene sequencing. Altogether, these results suggest that the production of galactose- and fucose-containing matrix carbohydrates is related to streptococcal metabolism and, thereby, pH profiles in dental biofilms. In conclusion, pH-FLBA using lectins with different carbohydrate specificities is a useful method to investigate the association between biofilm pH and the complex carbohydrate architecture of bacterial biofilms.IMPORTANCEBiofilm pH is a key regulating factor in several biological and biochemical processes in environmental, industrial, and medical biofilms. At the microscale, microbial biofilms are characterized by steep pH gradients and an extracellular matrix rich in carbohydrate components with diffusion-modifying properties that contribute to bacterial acid-base metabolism. Here, we propose a combined analysis of pH ratiometry and fluorescence lectin-binding analysis, pH-FLBA, to concomitantly investigate the matrix architecture and pH developments in microbial biofilms, using complex saliva-derived biofilms as an example. Spatiotemporal changes in biofilm pH are monitored non-invasively over time by pH ratiometry, while FLBA with lectins of different carbohydrate specificities allows mapping the distribution of multiple relevant matrix components in the same biofilm areas. As the biofilm structure is preserved, pH-FLBA can be used to investigate the in situ relationship between the biofilm matrix architecture and biofilm pH in complex multispecies biofilms., Competing Interests: The authors declare no conflict of interest.

Background and Objectives: The COVID-19 pandemic worsened the shortage of clinical training opportunities for health professions learners. During the pandemic, additional barriers to precepting health professions learners emerged. Understanding preceptors' perceptions of barriers is a first step to providing learners with the best clinical learning opportunities., Methods: In February 2021, the Emory Primary Care Consortium surveyed primary care providers eligible to precept health professions learners to determine their current precepting status and associated barriers encountered during and since COVID-19., Results: A total of 61 physicians and 11 nurse practitioners (NPs) or physician assistants (PAs) completed the survey. Of the 41 current preceptors, 29 precepted only MD students, 2 MD and PA students, 7 NP students only, and 3 PA students only. Of the 31 respondents who were not precepting, most (21) had precepted before March 2020 and not since. Pandemic-related precepting challenges included low patient volume (12), lack of comfort teaching in a telehealth setting (7), increased external pressure (eg, children at home; 8), and other reasons (12). Overall, 20 respondents were interested in training on incorporating students into the telehealth clinical workflow and 13 in training on teaching and providing feedback remotely., Conclusion: The COVID-19 pandemic placed additional burdens on preceptors in primary care. Preceptors could benefit from training on incorporating students into telehealth visits. Increased understanding of preceptor needs could lead to new resource offerings and improved future medical education., (© 2024 by the Society of Teachers of Family Medicine.)

Within a given species, considerable inter-individual, spatial, and temporal variation in the composition of the host microbiome exists. In group-living animals, social interactions homogenize microbiome composition among group members, nevertheless divergence in microbiome composition among related groups arise. Such variation can result from deterministic and stochastic processes. Stochastic changes, or ecological drift, can occur among symbionts with potential for colonizing a host and within individual hosts, and drive divergence in microbiome composition among hosts or host groups. We tested whether ecological drift associated with dispersal and foundation of new groups cause divergence in microbiome composition between natal and newly formed groups in the social spider Stegodyphus dumicola. We simulated the initiation of new groups by splitting field-collected nests into groups of 1, 3, and 10 individuals respectively, and compared variation in microbiome composition among and within groups after 6 weeks using 16S rRNA gene sequencing. Theory predicts that ecological drift increases with decreasing group size. We found that microbiome composition among single founders was more dissimilar than among individuals kept in groups, supporting this prediction. Divergence in microbiome composition from the natal nest was mainly driven by a higher number of non-core symbionts. This suggests that stochastic divergence in host microbiomes can arise during the process of group formation by individual founders, which could explain the existence of among-group variation in microbiome composition in the wild. Individual founders appear to harbour higher relative abundances of non-core symbionts compared with founders in small groups, some of which are possible pathogens. These symbionts vary in occurrence with group size, indicating that group dynamics influence various core and non-core symbionts differently., (© 2023 The Authors. Journal of Evolutionary Biology published by John Wiley & Sons Ltd on behalf of European Society for Evolutionary Biology.)

Dental biofilm pH is the most important determinant of virulence for the development of caries lesions. Confocal microscopy-based pH ratiometry allows monitoring biofilm pH with high spatial resolution. Experiments performed on simplified biofilm models under static conditions identified steep pH gradients as well as localized acidogenic foci that promote enamel demineralization. The present work used pH ratiometry to perform a comprehensive analysis of the effect of whole saliva flow on the microscale pH in complex, in situ-grown 48-h and 96-h biofilms ( n = 54) from 9 healthy participants. pH was monitored in 12 areas at the biofilm bottom and top, and saliva flow with film thicknesses corresponding to those in the oral cavity was provided by an additively manufactured microfluidic flow cell. Biofilm pH was correlated to the bacterial composition, as determined by 16S rRNA gene sequencing. Biofilm acidogenicity varied considerably between participants and individual biofilms but also between different areas inside one biofilm, with pH gradients of up to 2 units. pH drops were more pronounced in 96-h than in 48-h biofilms ( P = 0.0121) and virtually unaffected by unstimulated saliva flow (0.8 mm/min). Stimulated flow (8 mm/min) raised average biofilm pH to near-neutral values but it did not equilibrate vertical and horizontal pH gradients in the biofilms. pH was significantly lower at the biofilm base than at the top ( P < 0.0001) and lower downstream than upstream ( P = 0.0046), due to an accumulation of acids along the flow path. pH drops were positively correlated with biofilm thickness and negatively with the thickness of the saliva film covering the biofilm. Bacterial community composition was significantly different between biofilms with strong and weak pH responses but not their species richness. The present experimental study demonstrates that stimulated saliva flow, saliva film thickness, biofilm age, biofilm thickness, and bacterial composition are important modulators of microscale pH in dental biofilms., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Neptune-sized planets exhibit a wide range of compositions and densities, depending on factors related to their formation and evolution history, such as the distance from their host stars and atmospheric escape processes. They can vary from relatively low-density planets with thick hydrogen-helium atmospheres 1,2 to higher-density planets with a substantial amount of water or a rocky interior with a thinner atmosphere, such as HD 95338 b (ref.  3 ), TOI-849 b (ref.  4 ) and TOI-2196 b (ref.  5 ). The discovery of exoplanets in the hot-Neptune desert 6 , a region close to the host stars with a deficit of Neptune-sized planets, provides insights into the formation and evolution of planetary systems, including the existence of this region itself. Here we show observations of the transiting planet TOI-1853 b, which has a radius of 3.46 ± 0.08 Earth radii and orbits a dwarf star every 1.24 days. This planet has a mass of 73.2 ± 2.7 Earth masses, almost twice that of any other Neptune-sized planet known so far, and a density of 9.7 ± 0.8 grams per cubic centimetre. These values place TOI-1853 b in the middle of the Neptunian desert and imply that heavy elements dominate its mass. The properties of TOI-1853 b present a puzzle for conventional theories of planetary formation and evolution, and could be the result of several proto-planet collisions or the final state of an initially high-eccentricity planet that migrated closer to its parent star., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease characterized by damage to the alveolar epithelium, leading to fibrosis and excessive accumulation of extracellular matrix in the interstitium of the lung. In the present study we performed high-resolution proteomic profiling of bronchoalveolar lavage (BAL) from IPF patients and controls, and found that the complement pathway was highly upregulated in IPF. The proteins C5, C6, C7, C8, and C9, all of which are part of the complement end product, TCC, were all upregulated. We also found that TCC levels were increased in plasma among IPF patients compared to controls, after adjustment for age, sex and BMI [mean (SD) 0.62 (0.24) vs. 0.33 (0.10), p  = 0.031]. These findings suggest a role for the complement system in the pathogenesis of IPF., Competing Interests: MTD has received research funding (to his institution) and speaker/consulting fees from Boehringer Ingelheim and Roche, unrelated to the current study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sikkeland, Ueland, Lund, Durheim and Mollnes.)

Disentangling modes and fidelity of symbiont transmission are key for understanding host-symbiont associations in wild populations. In group-living animals, social transmission may evolve to ensure high-fidelity transmission of symbionts, since non-reproducing helpers constitute a dead-end for vertical transmission. We investigated symbiont transmission in the social spider Stegodyphus dumicola, which lives in family groups where the majority of females are non-reproducing helpers, females feed offspring by regurgitation, and individuals feed communally on insect prey. Group members share temporally stable microbiomes across generations, while distinct variation in microbiome composition exists between groups. We hypothesized that horizontal transmission of symbionts is enhanced by social interactions, and investigated transmission routes within (horizontal) and across (vertical) generations using bacterial 16S rRNA gene amplicon sequencing in three experiments: (i) individuals were sampled at all life stages to assess at which life stage the microbiome is acquired. (ii) a cross-fostering design was employed to test whether offspring carry the microbiome from their natal nest, or acquire the microbiome of the foster nest via social transmission. (iii) adult spiders with different microbiome compositions were mixed to assess whether social transmission homogenizes microbiome composition among group members. We demonstrate that offspring hatch symbiont-free, and bacterial symbionts are transmitted vertically across generations by social interactions with the onset of regurgitation feeding by (foster)mothers in an early life stage. Social transmission governs horizontal inter-individual mixing and homogenization of microbiome composition among nest mates. We conclude that temporally stable host-symbiont associations in social species can be facilitated and maintained by high-fidelity social transmission., (© 2023. The Author(s).)

Background: For interpretation of pulmonary function tests (PFTs), reference values based on sex, age, height and ethnicity are needed. In Norway, the European Coal and Steel Community (ECSC) reference values remain widely used, in spite of recommendations to implement the more recent Global Lung Function Initiative (GLI) reference values., Objective: To assess the effects of changing from ECSC to GLI reference values for spirometry, DLCO and static lung volumes, using a clinical cohort of adults with a broad range in age and lung function., Methods: PFTs from 577 adults (18-85 years, 45% females) included in recent clinical studies were used to compare ECSC and GLI reference values for FVC, FEV1, DLCO, TLC and RV. Percent predicted and lower limit of normal (LLN) were calculated. Bland-Altman plots were used to assess agreement between GLI and ECSC % predicted values., Results: In both sexes, GLI % predicted values were lower for FVC and FEV1, and higher for DLCO and RV, compared to ECSC. The disagreement was most pronounced in females, with mean (SD) difference 15 (5) percent points (pp) for DLCO and 17 (9) pp for RV (p < 0.001). With GLI, DLCO was below LLN in 23% of the females, with ECSC in 49% of the females., Conclusions: The observed differences between GLI and ECSC reference values are likely to entail significant consequences with respect to criteria for diagnostics and treatment, health care benefits and inclusion in clinical trials. To ensure equity of care, the same reference values should be consistently implemented across centers nationwide., (© 2023. The Author(s).)

Purpose: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an established treatment predominantly for malignancies. Chronic graft-versus-host disease (cGVHD) is the leading long-term complication after allo-HSCT, but knowledge on cGVHD and health-related quality of life (HRQOL) in long-term survivors of allo-HSCT performed in childhood, adolescence, and young adulthood (CAYA) is scarce. Therefore, we aimed to (1) assess prevalence and risk factors of active cGVHD using the 2014 National Institutes of Health-Consensus criteria, (2) investigate associations between cGVHD severity, patient-reported symptom burden, and HRQOL, and (3) compare HRQOL of survivors to population norms. Methods: We conducted a nationwide cross-sectional study in long-term survivors of CAYA allo-HSCT combining clinical examinations and patient-reported outcome measures. Results: We included 103 survivors, 55 (53%) females, median age of 19.6 years [range 0.3-29.9] at HSCT, 16.8 years [6.0-32.0] from HSCT, and 77 (75%) with underlying malignancy. Overall, 32 (31%) survivors were diagnosed with active cGVHD. The risk of active cGVHD was increased with prior acute GVHD and reduced with in vivo T cell depletion. cGVHD severity was associated with increased symptom burden, but not with adverse HRQOL. Compared to Norwegian population norms, allo-HSCT survivors reported significantly lower HRQOL. Conclusion: These results indicate a high prevalence of cGVHD in long-term survivors of CAYA allo-HSCT. Although we did not find an association between cGVHD severity and HRQOL, survivors reported significantly poorer HRQOL compared to population norms. Knowledge on the long-term consequences of cGVHD will be important for optimizing treatment and long-term follow-up care after CAYA allo-HSCT.

Lymphoma survivors after high-dose therapy with autologous stem-cell transplant (HDT-ASCT) are at risk of several late effects, which might impair their health-related quality of life (HRQoL). We assessed the total late effect burden in this population, and how it affects HRQoL. All lymphoma survivors treated with HDT-ASCT as adults in Norway between 1987 and 2008 were identified, and 271 (68%) attended both a comprehensive clinical assessment and completed a questionnaire. Severity of 45 conditions in 12 organ-system categories were graded as mild, moderate, severe or life-threatening, according to a modified version of CTCAEv4.03. At a median of 8 years after HDT-ASCT, 98% of survivors had at least one moderate or more severe late effect and 56% had severe or life-threatening late effects. Fourteen percent had low, 39% medium and 47% high late effect burden, defined as having moderate or more severe late effects in 0-1, 2-3 and >3 organsystems, respectively. Female sex, increasing age, B-symptoms at diagnosis and >1 treatment line prior to HDT-ASCT were independently associated with having high late effect burden. The survivors had significantly poorer physical and mental HRQoL assessed by the Short Form-36 compared to age- and sex-matched controls. The prevalence of poor physical and mental HRQoL increased with higher late effect burden (both P<0.001), and the low burden group had better physical HRQoL than controls (P<0.001). In conclusion, lymphoma survivors after HDT-ASCT have impaired HRQoL, seemingly driven by a high late effect burden. This highlights the importance of prevention, regular assessments for early detection and treatment of late effects and modifiable risk factors.

Carbohydrate components, such as glycoconjugates and polysaccharides, are constituents of the dental biofilm matrix that play an important role in biofilm stability and virulence. Exopolysaccharides in Streptococcus mutans biofilms have been characterized extensively, but comparably little is known about the matrix carbohydrates in complex, in situ-grown dental biofilms. The present study employed fluorescence lectin binding analysis (FLBA) to investigate the abundance and spatial distribution of glycoconjugates/polysaccharides in biofilms (n = 306) from 10 participants, grown in situ with (SUC) and without (H2O) exposure to sucrose. Biofilms were stained with 10 fluorescently labeled lectins with different carbohydrate specificities (AAL, ABA, ASA, HPA, LEA, MNA-G, MPA, PSA, VGA and WGA) and analyzed by confocal microscopy and digital image analysis. Microbial composition was determined by 16S rRNA gene sequencing. With the exception of ABA, all lectins targeted considerable matrix biovolumes, ranging from 19.3% to 194.0% of the microbial biovolume in the biofilms, which illustrates a remarkable variety of carbohydrate compounds in in situ-grown dental biofilms. MNA-G, AAL, and ASA, specific for galactose, fucose, and mannose, respectively, stained the largest biovolumes. AAL and ASA biovolumes were increased in SUC biofilms, but the difference was not significant due to considerable biological variation. SUC biofilms were enriched in streptococci and showed reduced abundances of Neisseria and Haemophilus spp., but no significant correlations between lectin-stained biovolumes and bacterial abundance were observed. In conclusion, FLBA demonstrates the presence of a voluminous biofilm matrix comprising a variety of different carbohydrate components in complex, in situ-grown dental biofilms., (© 2022 The Authors. Molecular Oral Microbiology published by John Wiley & Sons Ltd.)

This study aimed at exploring the association between detectable cardiac and pulmonary involvement in long-term juvenile dermatomyositis (JDM) and to assess if patients with cardiac and pulmonary involvement differ with regard to clinical characteristics. 57 JDM patients were examined mean 17.3 (10.5) years after disease onset; this included clinical examination, myositis specific/associated autoantibodies (immunoblot), echocardiography, pulmonary function tests and high-resolution computed tomography. Cardiac involvement was defined as diastolic and/or systolic left ventricular dysfunction and pulmonary involvement as low diffusing capacity for carbon monoxide, low total lung capacity and/or high-resolution computed tomography abnormalities. Patients were stratified into the following four groups: (i) no organ involvement, (ii) pulmonary only, (iii) cardiac only, and (iv) co-existing pulmonary and cardiac involvement. Mean age was 25.7 (12.4) years and 37% were males. One patient had coronary artery disease, seven had a history of pericarditis, seven had hypertension and three had known interstitial lung disease prior to follow-up. There was no association between cardiac (10/57;18%) and pulmonary (41/57;72%) involvement (p = 0.83). After stratifying by organ involvement, 21% of patients had no organ involvement; 61% had pulmonary involvement only; 7% had cardiac involvement only and 11% had co-existing pulmonary or cardiac involvement. Patients with co-existing pulmonary or cardiac involvement had higher disease burden than the remaining patients. Patients with either cardiac or pulmonary involvement only, differed in clinical and autoantibody characteristics. We found no increased risk of developing concomitant cardiac/pulmonary involvement in JDM. Our results shed light upon possible different underlying mechanisms behind pulmonary and cardiac involvement in JDM., (© 2022. The Author(s).)

Host-symbiont interactions may form obligatory or facultative associations that are context dependent. Long-term studies on microbiome composition from wild populations should assess the temporal and spatial dynamics of host-microbe associations. We characterized the temporal and spatial variation in the bacterial microbiome composition in six populations of the social spider Stegodyphus dumicola for 2.5 years, using 16S rRNA gene amplicon sequencing of whole spiders. Individuals within a nest exhibit highly similar microbiomes, which remain stable over several generations and are not predictably affected by seasonal variation in temperature or humidity. This stability in nest microbiome is likely due to social transmission, whereas drift-like processes during new nest foundations explain variation in host microbiomes between nests. This is supported by the lack of obligate symbionts (i.e. no symbionts are present in all spider individuals). Quantitative PCR analyses showed that the bacterial load of individual spiders is stable in healthy nests but can increase dramatically in perishing nests. These increases are not driven by specific bacterial taxa but likely caused by loss of host immune control under deteriorating conditions. Spider nests show an annual survival rate of approximately 45%, but nest death is not correlated to microbiome composition, and the bacteria found in S. dumicola are not considered to be high virulence pathogens., (© The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.)

While much attention has been paid to healthcare provider and trainee burnout, less is known about provider well-being (i.e., flourishing) or about the effects of well-being on immune function. This study examined the demographic and psycho-social correlates of well-being among healthcare trainees (resident physicians and physician assistant (PA) trainees) and evaluated the association of well-being with the "conserved transcriptional response to adversity" (CTRA) characterized by up-regulated expression of pro-inflammatory genes and down-regulated expression of innate antiviral genes. Participants (n = 58) completed self-reported assessments of sleep disturbance, loneliness, depressive symptoms, anxiety, stress, and well-being (flourishing). Blood sample RNA profiles were analyzed by RNA sequencing to assess the CTRA. Slightly over half (n = 32; 55.2%) of healthcare trainees were categorized as flourishing. Flourishing was less prevalent among primary caregivers, and more prevalent among trainees who exercised more frequently and those with fewest days sick. Loneliness (AOR = 0.75; 95% CI = 0.61, 0.91; p = 0.003) and stress (AOR = 0.65; 95% CI = 0.45, 0.94; p = 0.02) were associated with decreased odds of flourishing when controlling for other variables. Flourishing was associated with down-regulated CTRA gene expression, whereas loneliness was associated with up-regulated CTRA gene expression (both p < 0.05). Assessing these relationships in a larger, multi-site study is of critical importance to inform policy, curricula, and interventions to bolster sustainable trainee well-being.

Background: Survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk for pulmonary adverse events. Data on late-onset noninfectious pulmonary complications in long-term adult survivors of allo-HSCT are limited and incomplete., Objectives: This study aimed (1) to determine occurrence and degree of pulmonary sequelae in adult survivors of allo-HSCT and (2) to identify associations between pulmonary function, high-resolution CT (HRCT), and clinical characteristics., Method: In a nationwide, single-center cross-sectional study, 103 survivors (aged median [range] 35 [17-58] years, 53% females) were examined 17 (6-32) years after allo-HSCT and compared with healthy controls (n = 105). Methods included pulmonary function tests and HRCT., Results: Chronic graft-versus-host disease was diagnosed in 33% of survivors, including 12% with bronchiolitis obliterans syndrome (BOS). Mean lung volumes (TLC, FVC, and FEV1) and gas diffusing capacity were >80% of predicted for the survivors as a group, but significantly lower than in healthy controls. Pathological HRCT findings were detected in 48% of the survivors (71% airways disease, 35% interstitial lung disease, and 24% apical subpleural interstitial thickening). Air trapping (%) on HRCT correlated with % predicted FEV1, p < 0.001. In a multiple logistic regression model, both BOS and pathological findings on HRCT were associated with chemotherapy prior to allo-HSCT, p < 0.05., Conclusions: Long-term allo-HSCT survivors had significantly lower pulmonary function than age- and gender-matched healthy controls and nearly half had pathological findings on HRCT. Longitudinal data will determine if pulmonary sequelae will remain stable or progress. We recommend lifelong monitoring of pulmonary function in allo-HSCT survivors. HRCT provides additional information, but is not suited for surveillance., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Objective: The objective was to assess serum concentrations of club cell protein 16 (CC-16) and the surfactant proteins A (SPs-A) and D (SP-D) in male rock drillers ( N  = 123) exposed to crystalline silica and in 48 occupationally non-exposed. Methods: The arithmetic mean (AM) duration of exposure was 10.7 years. The geometric mean (GM) crystalline silica exposure was 36 µg/m 3 at the time of the study. The GM cumulative exposure was 239 µg/m 3 . Results: The concentrations of SP-D (GM 12.7 vs. 8.8 µg/L, p  < 0.001) and SP-A (AM 1847 vs. 1378 ng/L, p  = 0.051) were higher among rock drillers than among occupationally non-exposed. A positive significant association was observed between cumulative crystalline silica exposure and the SP-D concentrations ( β  = 0.07; p  < 0.05). Rock drillers with small airway obstruction with maximal mid-expiratory flow % (MMEF%) <70% ( N  = 29) had higher SP-D concentrations than rock drillers with MMEF% ≥ 70% ( N  = 91) (GM 17.3 vs . 11.4 µg/L, p  = 0.001). Rock drillers with MMEF% ≥70% ( N  = 91) had higher concentrations of SP-A (1957 vs. 1287 ng/L, p  = 0.01) and SP-D (11.4 vs. 9.0 µg/L, p  = 0.007) than non-exposed with MMEF% ≥70% ( N  = 39). Rock drillers with airway obstruction (FEV1/FVC < 0.70, N  = 11) had significantly lower CC-16 concentrations than rock drillers with FEV1/FVC ≥0.70 ( N  = 109) after adjusting for relevant potential confounders ( p  = 0.02). Conclusion: The results indicate that pulmonary surfactant is a target for crystalline silica toxicity. The alterations appear to be driven by pulmonary alterations in the small airways and by exposure itself. Further studies on pneumoproteins and pulmonary function in other groups of workers exposed to crystalline silica are needed.

Background: Health care provider and trainee burnout results in substantial national and institutional costs and profound social effects. Identifying effective solutions and interventions to cultivate resilience among health care trainees is critical. Although less is known about the mental health needs of physician assistants (PAs) or PA students, accumulating research indicates that they experience similarly alarming rates of burnout, depression, and emotional exhaustion. Mobile app-delivered mindfulness meditation may be an effective part of salubrious programming to bolster long-term resilience and health among PA students., Objective: This study aims to examine the impact of app-delivered mindfulness meditation on self-reported mental health symptoms among PA students. A secondary aim is to investigate changes in brain connectivity to identify neurobiological changes related to changes in mental health symptoms., Methods: We recruited PA students enrolled in their third semester of PA school and used a longitudinal, randomized, wait-list-controlled design. Participants randomized to the mindfulness group were provided 1-year subscriptions to the 10% Happier app, a consumer-based meditation app, and asked to practice every day for 8 weeks. Before randomization and again after completion of the 8-week program, all participants completed resting-state functional magnetic resonance imaging as well as self-report assessments of burnout, depression, anxiety, and sleep impairment. App use was acquired as a measure of mindfulness practice time., Results: PA students randomized to the mindfulness group reported improvements in sleep impairment compared with those randomized to the wait-list control group (η p 2 =0.42; P=.01). Sleep impairment decreased significantly in the mindfulness group (19% reduction; P=.006) but not in the control group (1% reduction; P=.71). There were no other significant changes in mental health for those randomized to app-delivered mindfulness. Across all students, changes in sleep impairment were associated with increased resting-state functional connectivity between the medial prefrontal cortex (a component of the default mode network) and the superior temporal gyrus, as well as between areas important for working memory. Changes in connectivity predicted categorical conversion from impaired to nonimpaired sleep in the mindfulness group., Conclusions: This pilot study is the first to examine app-based mindfulness for PA students' mental health and investigate the impact of mindfulness on PA students' brain function. These findings suggest that app-delivered mindfulness may be an effective tool to improve sleep dysfunction and that it may be an important part of the programming necessary to reduce the epidemic of suffering among health profession trainees., (©Jeremy L Smith, Jason W Allen, Carla I Haack, Kathryn L Wehrmeyer, Kayley G Alden, Maha B Lund, Jennifer S Mascaro. Originally published in JMIR Formative Research (https://formative.jmir.org), 19.10.2021.)

Spider silk is frequently attributed antimicrobial properties. This notion is based on studies reporting antimicrobial activity (AMA) of spider silk; however, close inspection of these studies reveals that the evidence is conflicting, and at best anecdotal. We performed a systematic study of antimicrobial properties of different silk types from seven species across the spider phylogeny. We found no evidence of AMA of silk in direct contact and disc diffusion assays against Gram-negative Escherichia coli and Pseudomonas putida , and the Gram-positive Bacillus subtilis . Furthermore, staining experiments and fluorescence microscopy showed the presence of live bacteria on silk surfaces indicating no antimicrobial effect on direct contact. A critical evaluation of the literature reveals that published tests of AMA are scarce and that all the studies claiming positive results are compromised by methodological shortcomings. Our analysis demonstrates that the common notion that spider silk is antimicrobial is not supported by empirical data., Competing Interests: None of the authors have financial or non-financial competing interests., (© 2021 The Authors.)

Social spiders of the species Stegodyphus dumicola live in communal nests with hundreds of individuals and are characterized by extremely low species-wide genetic diversity. The lack of genetic diversity in combination with group living imposes a potential threat for infection by pathogens. We therefore proposed that specific microbial symbionts inhabiting the spider nests may provide antimicrobial defense. To compare the bacterial and fungal diversity in 17 nests from three different locations in Namibia, we used 16S rRNA gene and internal transcribed spacer (ITS2) sequencing. The nest microbiomes differed between geographically distinct spider populations and appeared largely determined by the local environment. Nevertheless, we identified a core microbiome consisting of four bacterial genera (Curtobacterium, Modestobacter, Sphingomonas, Massilia) and four fungal genera (Aureobasidium, Didymella, Alternaria, Ascochyta), which likely are selected from surrounding soil and plants by the nest environment. We did not find indications for a strain- or species-specific symbiosis in the nests. Isolation of bacteria and fungi from nest material retrieved a few bacterial strains with antimicrobial activity but a number of antimicrobial fungi, including members of the fungal core microbiome. The significance of antimicrobial taxa in the nest microbiome for host protection remains to be shown., (Copyright © 2021 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Purpose: Survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk for cardiopulmonary adverse events. Data on long-term effects on cardiorespiratory fitness are limited. To address the gap in knowledge, we aimed to determine peak oxygen uptake (V̇O 2 peak) and identify associations between cardiorespiratory fitness and clinical characteristics, self-reported physical activity, cardiac, and pulmonary function., Methods: In a nationwide, single-center cross-sectional study, 90 survivors [aged median (range) 35 (17-54) years, 56% females] were examined, 17 (6-26) years after allo-HSCT. Myeloablative conditioning comprised busulfan/cyclophosphamide or cyclophosphamide only. Methods included pulmonary function tests, echocardiography, and cardiopulmonary exercise test., Results: Chronic graft-versus-host disease (cGVHD) was found in 31% of the subjects, of whom 40% had bronchiolitis obliterans syndrome (BOS). Seventy-one percent of the survivors did not meet WHO recommendations for physical activity and 42% were overweight. Reduced gas diffusion (DL CO ) and systolic ventricular dysfunction (LVEF) were found in 44% and 31%, respectively. For the group, mean (95% CI), V̇O 2 peak was 36.4 (34.7-38.0) mL/min/kg [89 (85-93)% of predicted]. V̇O 2 peak was low at 43%. Cardiopulmonary factors and deconditioning were equally common limitations for exercise. In a multiple linear regression model, low V̇O 2 peak was associated with low DL CO , low LVEF, BOS, overweight, and inactivity., Conclusion: Half of the survivors had reduced cardiorespiratory fitness median 17 years after allo-HSCT. Cardiopulmonary factors and deconditioning were equally common limitations to exercise. We encourage long-term cardiopulmonary monitoring of allo-HSCT survivors and targeted advice on modifiable lifestyle factors.

Some social arthropods engage in mutualistic symbiosis with antimicrobial compound-producing microorganisms that provide protection against pathogens. Social spiders live in communal nests and contain specific endosymbionts with unknown function. Bacteria are also found on the spiders' surface, including prevalent staphylococci, which may have protective potential. Here we present the genomic and phenotypic characterization of strain i1, isolated from the surface of the social spider Stegodyphus dumicola. Phylogenomic analysis identified i1 as novel strain of Staphylococcus sciuri within subgroup 2 of three newly defined genomic subgroups. Further phenotypic investigations showed that S. sciuri i1 is an extremophile that can grow at a broad range of temperatures (4 °C-45 °C), high salt concentrations (up to 27%), and has antimicrobial activity against closely related species. We identified a lactococcin 972-like bacteriocin gene cluster, likely responsible for the antimicrobial activity, and found it conserved in two of the three subgroups of S. sciuri. These features indicate that S. sciuri i1, though not a specific symbiont, is well-adapted to survive on the surface of social spiders and may gain a competitive advantage by inhibiting closely related species.

Objectives: Previous research indicates that mindfulness meditation reduces anxiety and depression and enhances well-being. We examined the impact of app-delivered mindfulness meditation on resting state functional MRI (fMRI) connectivity among physician assistant (PA) students and surgery residents., Methods: PA students and residents were randomized to receive a popular meditation app or to wait-list control group. Before and after the 8-week meditation period, we acquired fMRI scans of participants' resting state, and participants completed a self-report measure of mindfulness. We used a 2 × 2, within- and between-group factorial design and leveraged a whole-brain connectome approach to examine changes in within- and between-network connectivity across the entire brain, and to examine whether changes in connectivity were associated with app use or to changes in self-reported mindfulness., Results: Meditation practitioners exhibited significantly stronger connectivity between the frontoparietal network and the left and right nucleus accumbens and between the default mode (DMN) and salience networks, among other regions. Mindfulness practice time was correlated with increased connectivity between the lateral parietal cortex and the supramarginal gyrus, which were also positively correlated with increased scores on the "Describing" subscale of the Five Facet Mindfulness Questionnaire between baseline and post-meditation. These findings are consistent with previous research indicating that mindfulness-based interventions alter functional connectivity within the DMN and between the DMN and other networks both during meditation and at rest, as well as increased connectivity in systems important for emotion and reward., Conclusions: Recent commentaries call for healthcare provider and trainee wellness programs that are sustainable and preventive in nature rather than reactive; these data indicate that even brief sessions of app-delivered mindfulness practice are associated with functional connectivity changes in a dose-dependent manner., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© Springer Science+Business Media, LLC, part of Springer Nature 2020.)

Objectives: Chronic obstructive pulmonary disease and silicosis are associated with exposure to crystalline silica. We determined the exposure to respirable crystalline silica and estimated exposure-response relationships between cumulative exposure and pulmonary function in outdoor rock drillers., Methods: 136 rock drillers and 48 referents were recruited from three heavy construction companies. 98 air samples were collected by personal sampling for determination of respirable particulate matter and crystalline silica. Information about individual job tasks, type of drilling equipment and years of exposure in different job categories was obtained by interview. Cumulative exposure to crystalline silica was calculated for all workers. Pulmonary function was assessed by spirometry. A subgroup of 39 subjects with high cumulative exposure to crystalline silica underwent high-resolution computed tomography (HRCT)., Results: Cumulative exposure (mean (min-max)) to crystalline silica was 0.69 mg٠years m -3 (0.01-5.89) in the exposed group. Mean time of exposure among rock drillers was 10.7 years (1-42). Compared with referents, the rock drillers had a lower forced expiratory volume in one second/forced vital capacity ratio (79.4 vs 81.4, p<0.05) and maximal mid-expiratory flow% (85.6 vs 93.9, p<0.05). Further, by stratifying the exposed workers into three equally large groups, a dose-response relationship was demonstrated in the highest exposed group, also in never smokers, at a mean cumulative exposure of 21.7 years at 0.08 mg٠m -3 /years. Silicosis was not detected in HRCT, but other patterns of fibrosis and emphysema were seen., Conclusions: Outdoor rock drillers exposed to crystalline silica had significantly lower pulmonary function than referents, and signs of airflow obstruction. Silicosis was not detected., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Living with severe lung disease like chronic obstructive pulmonary disease (COPD) is a very stressful situation. The way patients cope may impact their symptoms of anxiety and depression and physical function as well. We studied how ways of coping are associated with levels of emotional distress and lung function in patients with COPD being evaluated for lung transplantation., Methods: Sixty-five (mean age 57 years, 46% females) patients completed the General Health Questionnaire-30 (GHQ-30) assessing emotional distress and the Ways of Coping Questionnaire. Measurements of lung function and 6-minute walk test were included., Results: Seventeen (26%) patients had elevated emotional distress. Logistic regression of chronic GHQ score with gender, age, body mass index, lung function, and coping scales as covariates showed that escape avoidance and self-controlling coping and forced vital lung capacity were significantly associated with high emotional distress. Odds ratio of emotional distress increased with 5.2 per tertile ( P = .011) in escape avoidance coping score. Moreover, we revealed that emotionally distressed patients cope with their current situation by refusing to believe the current situation and taking their distress out on other people., Conclusion: Among patients with COPD, a high level of emotional distress was uniquely associated with escape-avoidance coping and lung function. Future work should ascertain whether coping style predicts distress or whether distress increases the use of escape-avoidance coping. Nevertheless, our findings indicate that if either element is present, health care professionals should be attentive to the need for interventions to improve patients' well-being.

Background: Peak oxygen uptake (VO 2peak ) remains low after lung transplantation (LTx). We evaluated the effect of high-intensity interval training (HIIT) on VO 2peak , muscular strength, health-related quality of life (HRQOL), pulmonary function, and physical function after LTx., Methods: In this randomized controlled trial, 54 participants were enrolled from 6 to 60 months after LTx. The HIIT group (n = 25) followed a supervised HIIT program, consisting of endurance and strength trainings 3 times a week for 20 weeks. The control group (n = 29) received usual care. The primary outcome was a change in VO 2peak measured by cardiopulmonary exercise testing. The secondary outcomes were changes in 1-repetition maximum (1RM) for arm press and leg press, HRQOL (36-Item Short-Form Health Survey [SF-36]), pulmonary function (forced expiratory volume in 1 sec, diffusing capacity of the lungs for carbon monoxide), and physical function (1RM in handgrip, 15-sec stair run, and 30-sec chair stand)., Results: A total of 46 participants completed the study, including 23 of 25 in the intervention group. For the primary outcome, the intention-to-treat analysis revealed a non-significant between-group difference for change in VO 2peak of 0.7 ml/(kg.min) (95% CI = ‒0.3, 1.8) (p = 0.17). The between-group differences for 1RM arm press and leg press and mental aspect of SF-36 were 4.9 kg (95% CI = ‒0.1, 9.9) (p = 0.05), 11.6 kg (95% CI = 0.1, 23.0) (p < 0.05), and 5.7 kg (95% CI = 0.9, 10.4) (p = 0.02), respectively. There were no between-group differences in pulmonary function or physical function. When excluding participants with an attendance of <70% (n = 16), the between-group difference for VO 2peak was 1.2 ml/(kg.min) (95% CI = 0.1, 2.4) (p = 0.032)., Conclusions: HIIT improved muscular strength and HRQOL but did not improve VO 2peak more than usual care after LTx. However, with acceptable adherence, HIIT appears to have beneficial effects on VO 2peak ., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)