Search

Many natural resources are inefficiently used in advanced western economies Overuse of common property resources such as air occurs The assignment of property rights through grandfathering established uses can have disincentive effects as an entry barrier to new industry and allow the continuation of pernicious uses A Henry George type alternative remedial system of legal and tax treatment is developed It systematically covers all natural resources and their deteriorations, as well as improvements This updating should be extremely useful to everyone concerned with ecology. Also the task of industrial siting can be accomplished so as to ensure an efficient use of natural resources Present problems of dealing with pollution and hazardous waste sites under tort law would be avoided This part of the two-part paper covers the basic theoretical considerations The next issue of this Journal will include the application of the theory [ABSTRACT FROM AUTHOR]

Abstract Background The aim of the present study was to investigate the usability of verbal rating scale anchors in patients suffering from a depressive episode and whether differences between frequency or intensity scales could be determined. Frequency and intensity terms were evaluated concerning their interindividual congruency, intraindividual stability across time, and distinguishability of adjacent terms. Methods In a longitudinal design, 44 patients (age M=39.1, SD=15.2, 68.2% female) with a depressive disorder filled out several established questionnaires (e.g. BDI or SCL-90) and questionnaires containing frequency and intensity terms which should be indicated by the percentage of time or intensity that is reflected by each term at two different measuring times within one week. Data analysis contained t-tests for paired samples and effect sizes d according to Cohen. Results Intensity terms showed weaker intraindividual stability across time as compared to frequency terms. Participants were able to reliably distinguish four frequency and intensity terms at both measuring times. Overall congruency between patients was larger for intensity terms in comparison to frequency terms. Conclusions The present results indicate that both frequency and intensity terms can be applied as verbal anchors for clinical self-report scales. However, if longitudinal assessment is intended, our results indicate that frequency terms should be used as they showed slightly greater stability across time. Generally, the present study suggests that no more than four different verbal anchors should be used together in rating scales as especially older patients and those with low lexical experience would not be able to reasonably differentiate more than these.

Background/Objectives : This study aimed to evaluate and establish the incidence of all types of neurological complications at our high-volume reference center for open TAAA repair in the Netherlands and Germany. Additionally, we sought to identify predictors for various neurological complications. Methods : This retrospective study was conducted in accordance with the STROBE guidelines, with the aim of reporting neurological outcomes for all patients who underwent open thoracoabdominal aortic aneurysm repair at two centers (Maastricht-Aachen) from 2000 to 2023, and to examine the association between these outcomes and pre- and perioperative parameters. The primary endpoints of the study were all-cause mortality, spinal cord ischemia (SCI), stroke, intracerebral bleeding (ICB), critical illness polyneuropathy/myopathy (CIP/CIM), and recurrent laryngeal nerve paralysis. Results : A total of 577 patients were operated on for open TAAA repair in two centers. The total in-hospital mortality rate was 20.6%, while the elective cases in-hospital mortality rate was 14.6%. In all, 28.2% of patients experienced neurological complications. The spinal cord ischemia rate was 7.5%, intracerebral bleeding 3.6%, stroke 5.9%, critical illness polyneuropathy 3.5%, and laryngeal nerve paresis 5.7%. Crawford extent II was significantly associated with increased neurological complications (OR 2.05, 95% CI 1.39-3.03, p = 0.003), while Crawford extent III and IV were significantly associated with fewer postoperative neurological complications (OR 0.61 (0.38-0.98) p = 0.04) (OR 0.52 (0.30-0.92) p = 0.02). Preoperative ASA score > 3 (OR 1.76, 95% CI 1.16-2.67, p = 0.007), COPD (OR 1.82, 95% CI 1.19-2.78, p = 0.006), massive intraoperative transfusion (OR 1.48, 95% CI 1.01-2.17, p = 0.04), and reinterventions during hospital stay (OR 1.98, 95% CI 1.36-2.89, p < 0.001) and surgery time ( p =< 0.001) were significantly associated with neurological complications. Patients with neurological complications had higher rates of other postoperative morbidities. Conclusions : Neurological complications after open TAAA repair remain a significant concern, with identified risk factors associated with increased morbidity, mortality, and resource utilization. Identifying at-risk patients could potentially lead to a reduction in neurological complications., Competing Interests: The authors declare no conflicts of interest.

Objective: The present study investigated the impact of two different light intensities on the pain-modulated pupillary light response (PLR). Additionally, it aimed to demonstrate parasympathetic and sympathetic influences on PLR parameters in response to pain, as predicted by functional models., Method: A total of 24 participants were included in a randomized, repeated-measures design. The PLR was measured in response to both dark and bright light stimuli within two test cycles. Pain was induced using the cold pressor test (CPT), which involved immersing participants' feet in ice water. PLR measurements were taken during baseline and ice-water immersion within each test cycle. The assessed PLR parameters included initial diameter (INIT), latency (LAT), amplitude (AMP), and re-dilation time (ReDIL25). Along with these parameters, heart rate (HR) and pain ratings were also computed and analyzed., Main Results: The CPT caused moderate pain in participants, and the resulting PLR parameters were found to be congruent with the expected parasympathetic and sympathetic nervous system activities. Although the luminance of the stimulus did influence PLR parameters, no interaction with pain exposure was found., Significance: The results showed that different aspects of pain experienced by an individual, as modulated through the sympathetic and parasympathetic nervous systems, are visible in their pupillary reactions to light. Notably, within the range used in the current study, light intensity did not significantly affect the pain-related PLR effects., Competing Interests: The 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 © 2024 Kursawe, Ehrlichmann, Weber, Krabbe and Kraus.)

Background: Molecular pathways found to be important in pulmonary fibrosis are also involved in cancer pathogenesis, suggesting common pathways in the development of pulmonary fibrosis and lung cancer., Research Question: Is pulmonary fibrosis from exposure to occupational carcinogens an independent risk factor for lung cancer?, Study Design and Methods: A comprehensive search of PubMed, Embase, Web of Science and Cochrane databases with over 100 search terms regarding occupational hazards causing pulmonary fibrosis was conducted. After screening and extraction, quality of evidence and eligibility criteria for meta-analysis were assessed. Meta-analysis was performed using a random-effects model., Results: 52 studies were identified for systematic review. Meta-analysis of subgroups identified silicosis as a risk factor for lung cancer when investigating odds ratios for silicosis in autopsy studies (OR 1.47, 95% CI 1.13-1.90) and for lung cancer mortality in patients with silicosis (OR 3.21, 95% CI 2.67-3.87). Only considering studies with an adjustment for smoking as a confounder identified a significant increase in lung cancer risk (OR 1.58, 95% CI 1.34-1.87). However, due to a lack of studies including cumulative exposure, no adjustments could be included. In a qualitative review, no definitive conclusion could be reached for asbestosis and silicosis as independent risk factors for lung cancer, partly because the studies did not take cumulative exposure into account., Interpretation: This systematic review confirms the current knowledge regarding asbestosis and silicosis, indicating a higher risk of lung cancer in exposed individuals compared to exposed workers without fibrosis. These individuals should be monitored for lung cancer, especially when asbestosis or silicosis is present., Competing Interests: Conflict of interest: T. Kraus and J. Krabbe give talks on this topic at workshops, seminars, and conferences for which have been paid for by the organisers including travel and accommodation. J. Krabbe, S. Drießen and T. Kraus have done research in the past funded by German institutions for statutory accident insurance and prevention with unrestricted grants to the University Hospital RWTH Aachen. K.M. Steffens has nothing to disclose., (Copyright ©The authors 2024.)

Background: Acute aortic dissection type A (AADA) is a surgical emergency with relevant mortality and morbidity despite improvements in current management protocols. Identifying patients at risk of a fatal outcome and controlling the factors associated with mortality remain of paramount importance., Methods: In this retrospective observational study, we reviewed the medical records of 117 patients with AADA, who were referred to our centre and operated on between 2005 and 2021. Preoperative, intraoperative, and postoperative variables were analysed and tested for their correlation with in-hospital mortality., Results: The overall survival rate was 83%. Preoperatively, factors associated with mortality were age ( p = 0.02), chronic hypertension ( p = 0.02), any grade of aortic valve stenosis in the patient's medical history ( p = 0.03), atrial fibrillation ( p = 0.04), and oral anticoagulation ( p = 0.04). Non-survivors had significantly longer operative times ( p = 0.002). During the postoperative phase, mortality was strongly associated with acute kidney injury (AKI) ( p < 0.001), acute heart failure ( p < 0.001), stroke ( p = 0.02), focal neurological deficits ( p = 0.02), and sepsis ( p = 0.001). In the multivariate regression analysis, the onset of postoperative focal neurological deficits was the best predictor of a fatal outcome after adjusting for ARDS (odds ratio: 5.8, 95%-CI: 1.2-41.7, p = 0.04)., Conclusions: In this retrospective analysis, atrial fibrillation, oral anticoagulation, hypertension, and age were significantly correlated with mortality. Postoperatively, acute kidney injury, acute heart failure, sepsis, and focal neurological deficits were correlated with in-hospital mortality, and focal neurological deficit has been identified as a significant predictor of fatal outcomes. Early detection and interdisciplinary management of at-risk patients remain crucial throughout the postoperative phase.

Background: Percutaneous deep vein arterialization (pDVA) is considered a treatment modality in patients with no-option critical limb ischemia. However, there is still a paucity of evidence regarding its safety and efficacy., Data Sources: MEDLINE (via PubMed), Embase and Web of Science databases as well as the CENTRAL registry up to the end of June 2023., Methods: This review adhered to the PRISMA guidelines (PROSPERO registration no. CRD42023445171). The risk of bias was assessed using the methodological index for non-randomized studies (MINORS). Primary endpoints included technical success, overall survival and limb salvage during the follow-up. Amputation-free survival at 30 days, 6 months and 1 year as well as complete wound healing, major adverse limb events and reintervention were investigated as secondary outcomes., Results: Five observational studies, comprising 208 patients (142 Rutherford class 5/77 Rutherford class 6), were included. MINORS revealed a low risk of bias. The meta-analysis reached a pooled technical success rate of 96.2% (95% CI: 91.5-98.4), an overall survival of 82.8% (95% CI: 70.5-95.2) and a limb salvage rate of 77.2% (95% CI: 65.2-89.1) during the follow-up. The amputation-free survival at 30 days, 6 months and 1 year was 87.8%, 68.7% and 65.6%, respectively. Furthermore, pDVA resulted in a complete wound healing rate of 53.4% (95% CI: 30.3-76.5). The pooled reintervention rate was as high as 46.7% (37.1-56.3%)., Conclusions: PDVA seems a feasible bail-out strategy for patients with no option for routine treatment of CLTI. However, due to the small number of studies, the strength of the evidence is low.

The endosymbiosis between the pathogenic fungus Rhizopus microsporus and the toxin-producing bacterium Mycetohabitans rhizoxinica represents a unique example of host control by an endosymbiont. Fungal sporulation strictly depends on the presence of endosymbionts as well as bacterially produced secondary metabolites. However, an influence of primary metabolites on host control remained unexplored. Recently, we discovered that M. rhizoxinica produces FO and 3PG-F420, a derivative of the specialized redox cofactor F420. Whether FO/3PG-F420 plays a role in the symbiosis has yet to be investigated. Here, we report that FO, the precursor of 3PG-F420, is essential to the establishment of a stable symbiosis. Bioinformatic analysis revealed that the genetic inventory to produce cofactor 3PG-F420 is conserved in the genomes of eight endofungal Mycetohabitans strains. By developing a CRISPR/Cas-assisted base editing strategy for M. rhizoxinica, we generated mutant strains deficient in 3PG-F420 (M. rhizoxinica ΔcofC) and in both FO and 3PG-F420 (M. rhizoxinica ΔfbiC). Co-culture experiments demonstrated that the sporulating phenotype of apo-symbiotic R. microsporus is maintained upon reinfection with wild-type M. rhizoxinica or M. rhizoxinica ΔcofC. In contrast, R. microsporus is unable to sporulate when co-cultivated with M. rhizoxinica ΔfbiC, even though the fungus was observed by super-resolution fluorescence microscopy to be successfully colonized. Genetic and chemical complementation of the FO deficiency of M. rhizoxinica ΔfbiC led to restoration of fungal sporulation, signifying that FO is indispensable for establishing a functional symbiosis. Even though FO is known for its light-harvesting properties, our data illustrate an important role of FO in inter-kingdom communication., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)

Relaxation-related workplace interventions can be counterstrategies for stress due to office work and should be evaluated for success after implementation. This study reports on the evaluation and comparison of 3 relaxation techniques introduced as an intervention for health promotion. A Germany-wide multicenter evaluation of a 3-month relaxation intervention (30 min, once a week) including autogenic training, progressive muscle relaxation (PMR) or Tai Chi was conducted at 14 locations as an intervention study. Anonymous questionnaires ( n  = 244) were used to collect self-reports of perceived stress after the courses. Status before the courses (pre) and after completion (post) were reported at the end of the intervention. All 3 relaxation techniques were able to improve the subjective perception of stress (SPS) score. Autogenic training was reported to improve all singular items with large effects, whereas only 2 items showed change for Tai Chi and none for PMR. Singular items were also influenced by the location of the courses. All 3 methods were able to improve stress-related outcomes in terms of stress perception and individual aspects of stress management. For this specific intervention autogenic training yielded the largest and wide-ranging effects. Tai Chi was also effective, but additional effect due to an associated increase in physical activity were not found. For a workplace intervention PMR could not be recommended based on this study. The literature on workplace interventions is surprisingly scarce, and future studies should focus on the selection of appropriate participants while avoiding potential bias., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Heidi Lehmann is the head of the Management Safety and Health Team at the Social Accident Insurance Institution for the Energy, Textile, Electrical and Media products sectors (BG ETEM). Nelly Otte, Thomas Kraus, André Esser and Julia Krabbe have done other research funded by BG ETEM with unrestricted grants.

As part of the energy transition in Germany, high-voltage overhead power lines will be operated using hybrid systems that combine alternating and direct current (AC and DC). The degree to which humans perceive hybrid electric fields (EFs) is dependent on the proportion of both EF types. To investigate the impact of the DC component, a study assessed 49 participants with above-average EF detection ability under conditions with a low DC component of 1-4 kilovolts per meter (kV/m) and varying AC EFs between 1 and 14 kV/m. The detection thresholds of combined AC/DC EFs decreased with an increase in the DC component and ranged from 9.6 to 6.83 kV/m on average for the group. The results suggest that even minor variations in the DC component significantly affect human perception of hybrid EFs. These findings complement the results of an earlier study that investigated the AC component in hybrid EFs. Correlational analyses of both studies demonstrated the reliability of participants' performance. This study contributes to our understanding of EF-related effects on human perception and can aid in the planning of energy transmission near areas where humans work or live., (© 2023. The Author(s).)

As an endosymbiont of the ecologically and medically relevant fungus Rhizopus microsporus, the toxin-producing bacterium Mycetohabitans rhizoxinica faces myriad challenges, such as evading the host's defense mechanisms. However, the bacterial effector(s) that facilitate the remarkable ability of M. rhizoxinica to freely migrate within fungal hyphae have thus far remained unknown. Here, we show that a transcription activator-like (TAL) effector released by endobacteria is an essential symbiosis factor. By combining microfluidics with fluorescence microscopy, we observed enrichment of TAL-deficient M. rhizoxinica in side hyphae. High-resolution live imaging showed the formation of septa at the base of infected hyphae, leading to the entrapment of endobacteria. Using a LIVE/DEAD stain, we demonstrate that the intracellular survival of trapped TAL-deficient bacteria is significantly reduced compared with wild-type M. rhizoxinica, indicative of a protective host response in the absence of TAL proteins. Subversion of host defense in TAL-competent endobacteria represents an unprecedented function of TAL effectors. Our data illustrate an unusual survival strategy of endosymbionts in the host and provide deeper insights into the dynamic interactions between bacteria and eukaryotes., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Pulmonary function testing (PFT) is a central part of diagnosis and treatment monitoring in respiratory medicine. Few studies have investigated whether repeated PFT or training can significantly influence performance. To investigate potential training effects of repeated PFT, 30 healthy volunteers underwent daily and weekly repeated PFT with spirometry over 10 weeks. The study included 22 females and 8 males with a mean age of 31.8 years ± 15 (SD), a mean weight of 66.3 kg ± 14.5 (SD) and a mean BMI of 22.4 ± 3.3 (SD). The first 5 PFTs were performed on 5 consecutive days, followed by 3 PFTs once a week on the same day of the week. Subsequently, 5 measurements were taken daily for 5 consecutive days. After these 13 appointments in 5 weeks, participants were randomly assigned to the control or incentive group, with stratification for age and gender. The incentive group had the opportunity to win money (200 €) for the highest increase in forced vital capacity (FVC). PFTs were performed once a week on the same day of the week as before for 5 more times. Motivation was assessed by a questionnaire before the 1st, 9th and 18th measure of PFT at three time points throughout the study. An increase in PFT was observed with mean increases of 473 [ml] in FVC, 395 [ml] in forced expiratory volume in 1 s (FEV1) and 1.382 [litres/second] in peak expiratory flow (PEF) after four days of daily PFT. These increases did not persist and spirometric data returned to baseline after one week. After allocation, participants in the incentive group did not increase their FVC, FEV1 or PEF compared to the control group. The incentive group showed higher motivation than the control group, even before allocation. Repeated daily PFT could induce short-term increases, but PFT does not fluctuate significantly in the long term. External influences that affect motivation could not consistently increase PFT. For clinical practice, it can be concluded that PFT does not necessarily require extended training to ensure reliability if reproducibility criteria are met., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Physical activity-related workplace interventions can be counterstrategies for physical inactivity due to office work. Newly introduced programs should be evaluated for success. This study aimed to evaluate the intervention of a workplace active rest program and to compare a prospective and retrospective design of evaluation. A Germany-wide multicenter evaluation of a 3-month workplace active rest program (30 min, once a week) was carried out at 14 locations with a longitudinal pre/post design by means of an anonymous questionnaire (n pre  = 405, n post  = 369). The participants' program-related changes in targeted characteristics regarding posture, function, complaints and physical awareness were collected with a questionnaire in a prospective design and afterward retrospectively. The prospective evaluation showed a significant improvement in the target characteristic "postural muscles in the neck area". In the retrospective survey, all target characteristics improved significantly. There were no differences between locations. The workplace active rest program in this study had positive effects on the perception of postural neck muscle status regardless of prospective or retrospective approach. Selection of survey mode should depend on desired outcome and consecutive influencing factors. In this specific case, retrospective survey could give more indirect information about overall satisfaction with the program and job although being influenced by response bias. Recall bias should be relatively small for shorter time periods assessed. Future studies should account for corresponding bias and specifics of target characteristics regardless of the chosen approach to survey., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Heidi Lehmann is the head of the Management Safety and Health Team at the Social Accident Insurance Institution for the Energy, Textile, Electrical and Media products sectors (BG ETEM). Thomas Kraus, André Esser and Julia Krabbe have done other research funded by BG ETEM with unrestricted grants.

Background and Objectives : Peripheral arterial disease (PAD) contains a significant proportion of patients whose main pathology is located in the infragenicular arteries. The treatment of these patients requires a deliberate consideration due to the threat of possible complications of an intervention. In this retrospective study, the feasibility of a below-the-knee atherectomy (BTKA) via a 1.5 mm Phoenix atherectomy catheter and the patient outcome over the course of 6 months are investigated. Materials and Methods : The data of patients suffering from PAD with an infragenicular pathology treated via 1.5 mm Phoenix™ atherectomy catheter between March 2021 and February 2022 were retrospectively analyzed. Prior to the intervention, after 2 weeks and 6 months, the PAD stages were graded and ankle-brachial-indeces (ABI) were measured. Results : The study shows a significant improvement of ABI, both after 2 weeks and 6 months. Additionally, the number of PAD stage IV patients decreased by 15.2% over the course of 6 months, and 18.2% of the patients improved to PAD stage IIa. Only one bleeding complication on the puncture side occurred over the whole study, and no other complications were observed. Conclusions : Phoenix™ atherectomy usage in the BTKA area seems to be feasible and related to a favorable outcome in this retrospective study.&nbsp.

Background: Physicians' communication skills are important for patient-centered care. Although working with simulated patients (SPs) in case simulations is common for training communication skills, studies seldom include a wide range of challenging behaviors or explore students' own experiences of learning communication skills with SPs. Therefore, this study was aimed at investigating how medical students perceive communication training involving challenging consultations with SPs and the impact on their learning experiences., Methods: Twenty-three medical students from the same class were interviewed in focus groups about their experiences of simulation training with actors as SPs. In the simulation training, the students were instructed to deliver bad news, manage negative patient reactions, and encourage behavioral changes in reluctant patients. This was followed by feedback and a debriefing exercise. The interviews were analyzed with content analysis., Results: Students reported that actors as SPs made the simulations more realistic and enabled them to practice various communication skills for challenging consultations in a safe way and manage their own feelings, thereby promoting new learning experiences. Elements such as actors' flexibility in changing behaviors during role-play and exposure to different challenging behaviors, like negative emotions, were regarded as valuable. The importance of an accepting and permissive climate for the debriefing exercise was highlighted, though without taking too much time from the simulation training. Feedback directly from the SP was appreciated., Conclusions: Actors as SPs were perceived as a valuable part of challenging communication training and added elements to the learning process. Future studies should include a wider range of challenging behaviors in training with SPs and evaluate the effects of such training on students' use of communication skills., (© 2022. The Author(s).)

Background: Respiratory diseases represent a global health burden. Because research on therapeutic strategies of airway diseases is essential, the technique of precision-cut lung slices (PCLS) has been developed and widely studied. PCLS are an alternative ex vivo model and have the potential to replace and reduce in vivo animal models. So far, the majority of studies was conducted with short-term cultivated PCLS (≤ 72 h). As there is large interest in research of chronic diseases and chronic toxicity, feasibility of cultivating human PCLS long-term over 2 weeks and recently over 4 weeks was investigated by another research group with successful results. Our aim was to establish a model of long-term cultivated rat PCLS over a period of 29 days., Methods: Rat PCLS were cultured for 29 days and analysed regarding viability, histopathology, reactivity and gene expression at different time points during cultivation., Results: Cultivation of rat PCLS over a 29-day time period was successful with sustained viability. Furthermore, the ability of bronchoconstriction was maintained between 13 and 25 days, depending on the mediator. However, reduced relaxation, altered sensitivity and increased respiratory tone were observed. Regarding transcription, alteration in gene expression pattern of the investigated target genes was ascertained during long-term cultivation with mixed results. Furthermore, the preparation of PCLS seems to influence messenger ribonucleic acid (mRNA) expression of most target genes. Moreover, the addition of fetal bovine serum (FBS) to the culture medium did not improve viability of PCLS. In contrast to medium without FBS, FBS seems to affect measurements and resulted in marked cellular changes of metaplastic and/or regenerative origin., Conclusions: Overall, a model of long-term cultivated rat PCLS which stays viable for 29 days and reactive for at least 13 days could be established. Before long-term cultivated PCLS can be used for in-depth study of chronic diseases and chronic toxicity, further investigations have to be made., (© 2022. The Author(s).)

Zinc- and copper-containing welding fumes can cause systemic inflammation after exposure in humans. Recent ex vivo studies have shown that the observed inflammation originates from exposed immune cells. In vitro studies identified the soluble fraction of metal particles as the main effectors. Isolated perfused mouse lungs (IPLs) were perfused and ventilated for 270 min. Lungs were instilled with saline solution (control), welding fume particle suspension (WFs) or the soluble fraction of the welding fumes (SF-WFs). Bronchoalveolar lavage fluid (BALF) and perfusate samples were analyzed for cytokine levels and lung tissue mRNA expression levels were analyzed via RT-PCR. All lungs instilled with WFs did not complete the experiments due to a fatal reduction in tidal volume. Accordingly, IL-6 and MPO levels were significantly higher in BALF of WF lungs compared to the control. IL-6 and MPO mRNA expression levels were also increased for WFs. Lungs instilled with SF-WFs only showed mild reactions in tidal volume, with BALF and mRNA expression levels not significantly differing from the control. Zinc- and copper-containing welding fume particles adversely affect IPLs when instilled, as evidenced by the fatal loss in tidal volume and increased cytokine expression and secretion. The effects are mainly caused by the particles, not by the soluble fraction., Competing Interests: All authors have carried out research in the past funded by the Institution for Statutory Accident Insurance and Prevention in the woodworking and metalworking industry (BGHM), Mainz, Germany, with unrestricted grants to the University Hospital RWTH Aachen. J.K. and T.K. have held paid lectures about welding fume effects.

Background: Almost 2 years from the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there is still a lot unknown how the humoral response affects disease progression. In this study, we investigated humoral antibody responses against specific SARS-CoV2 proteins, their strength of binding, and their relationship with COVID severity and clinical information. Furthermore, we studied the interactions of the specific receptor-binding domain (RBD) in more depth by characterizing specific antibody response to a peptide library., Materials and Methods: We measured specific antibodies of isotypes IgM, IgG, and IgA, as well as their binding strength against the SARS-CoV2 antigens RBD, NCP, S1, and S1S2 in sera of 76 COVID-19 patients using surface plasmon resonance imaging. In addition, these samples were analyzed using a peptide epitope mapping assay, which consists of a library of peptides originating from the RBD., Results: A positive association was observed between disease severity and IgG antibody titers against all SARS-CoV2 proteins and additionally for IgM and IgA antibodies directed against RBD. Interestingly, in contrast to the titer of antibodies, the binding strength went down with increasing disease severity. Within the critically ill patient group, a positive association with pulmonary embolism, d-dimer, and antibody titers was observed., Conclusion: In critically ill patients, antibody production is high, but affinity is low, and maturation is impaired. This may play a role in disease exacerbation and could be valuable as a prognostic marker for predicting severity., Competing Interests: Patents: Provisional patent is filed based on the data generated from this work. Provisional title: Strength of Binding of Antibodies Against Infectious Diseases Measured With Evanescent Field Based Biosensors. COVID-19 Patients With High Titers of Low Affinity Antibodies Are Associated With Disease Severity. The 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 © 2022 Hendriks, Schasfoort, Koerselman, Dannenberg, Cornet, Beishuizen, van der Palen, Krabbe, Mulder and Karperien.)

Background We assessed the ability of baseline and serial measurements of mid-regional proadrenomedullin (MR-proADM) and mid-regional proatrial natriuretic peptide (MR-proANP) to predict 28-day mortality in critically ill patients with pneumonia compared with Acute Physiological and Chronic Health Evaluation IV (APACHE IV) model and Sequential Organ Failure Assessment (SOFA) score. Methodology Biomarkers were collected for the first five days in this retrospective observational cohort study. Biomarker clearance (as a percentage) was presented as biomarker decline in five days. We investigated the relationship between biomarkers and mortality in a multivariable Cox regression model. APACHE IV and SOFA were calculated after 24 hours from intensive care unit admission. Results In 153 critically ill patients with pneumonia, 28-day mortality was 26.8%. Values of baseline MR-proADM, MR-proANP, and APACHE IV were significantly higher in 28-day nonsurvivors, but not significantly different for SOFA score. Baseline MR-proADM and MR-proANP, APACHE IV, and SOFA had a low area under the curve in receiver operating characteristics (ROC) curves. No optimal cut-off points could be calculated. Biomarkers and severity scores were divided into tertiles. The highest tertiles baseline MR-proADM and MR-proANP were not significant predictors for 28-day mortality in a multivariable model with age and APACHE IV. SOFA was not a significant predictor in univariable analysis. Clearances of MR-proADM and MR-proANP were significantly higher in 28-day survivors. MR-proADM and MR-proANP clearances had similar low accuracy to identify nonsurvivors in ROC curves and were divided into tertiles. Low clearances of MR-proADM and MR-proANP (first tertiles) were significant predictors for 28-day mortality (hazard ratio [HR]: 2.38; 95% confidence interval [CI]: 1.21-4.70; p = 0.013 and HR: 2.27; 95% CI: 1.16-4.46; p = 0.017) in a model with age and APACHE IV. Conclusions MR-proADM and MR-proANP clearance performed better in predicting 28-day mortality in a model with age and APACHE IV compared with single baseline measurements in a mixed population of critically ill with pneumonia., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Van Oers et al.)

Retrograde perfusion may occur during disease, surgery or extracorporeal circulation. While it is clear that endothelial cells sense and respond to changes in blood flow, the consequences of retrograde perfusion are only poorly defined. Similar to shear stress or disturbed flow, retrograde perfusion might result in vasomotor responses, edema formation or inflammation in and around vessels. In this study we investigated in rats the effects of retrograde perfusion in isolated systemic vessels (IPV) and in pulmonary vessels of isolated perfused lungs (IPL). Anterograde and retrograde perfusion was performed for 480 min in IPV and for 180 min in the IPL. Perfusion pressure, cytokine levels in perfusate and bronchoalveolar lavage fluid (BALF), edema formation and mRNA expression were studied. In IPV, an increased perfusion pressure and initially also increased cytokine levels were observed during retrograde perfusion. In the IPL, increased edema formation occurred, while cytokine levels were not increased, though dilution of cytokines in BALF due to pulmonary edema cannot be excluded. In conclusion, effects of flow reversal were visible immediately after initiation of retrograde perfusion. Pulmonary edema formation was the only effect of the 3 h retrograde perfusion. Therefore, further research should focus on identification of possible long-term complications of flow reversal.

Introduction: Outreach is regularly identified as an effective strategy to engage underserved, hard-to-reach and hidden populations with essential life-sustaining health services. Despite the increasing expansion of outreach programmes, particularly in HIV prevention and health promotion with youth, sex workers, people living with mental health and substance use challenges, and those affected by homelessness, there has been limited synthesis of the evidence concerning the core components of outreach programming or indicators of its successful implementation. Without this understanding, current outreach programmes may be limited in achieving the desired aims. The aim of this scoping review is to explore how outreach has been operationalised and implemented in various community settings with people underserved in current healthcare contexts. Understanding the state of knowledge pertaining to outreach as programming and as practice involving the engagement of people considered hard-to-reach will enable the identification of promising trends and limitations in the field., Methods and Analysis: This scoping review follows the Arksey and O'Malley's framework. CINAHL, MEDLINE, PsycINFO and PubMed databases will be searched for peer-reviewed references focused on outreach with hard-to-reach and hidden groups from 1 January 2008 to 30 April 2020. Guided by explicit inclusion and exclusion criteria, three reviewers will independently assess references in two successive stages. Titles and abstracts will be reviewed followed by full-text assessment of papers meeting the review criteria. A descriptive overview, tabular and/or graphical summaries and a thematic analysis will be carried out on extracted data., Ethics and Dissemination: Ethics approval was not required as the only data source was peer-reviewed documents. Outreach knowledge users who are members of the project team will participate in all aspects of study design, implementation and result dissemination strategies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The present study reports on first-trimester reference ranges of plasma mineral Se/Zn/Cu concentration in relation to free thyroxine (FT4), thyrotropin (TSH) and thyroid peroxidase antibodies (TPO-Ab), assessed at 12 weeks' gestation in 2041 pregnant women, including 544 women not taking supplements containing Se/Zn/Cu. The reference range (2·5th-97·5th percentiles) in these 544 women was 0·72-1·25 µmol/l for Se, 17·15-35·98 µmol/l for Cu and 9·57-16·41 µmol/l for Zn. These women had significantly lower mean plasma Se concentration (0·94 (sd 0·12) µmol/l) than those (n 1479) taking Se/Zn/Cu supplements (1·03 (sd 0·14) µmol/l; P < 0·001), while the mean Cu (26·25 µmol/l) and Zn (12·55 µmol/l) concentrations were almost identical in these sub-groups. Women with hypothyroxinaemia (FT4 below reference range with normal TSH) had significantly lower plasma Zn concentrations than euthyroid women. After adjusting for covariates including supplement intake, plasma Se (negatively), Zn and Cu (positively) concentrations were significantly related to logFT4; Se and Cu (but not Zn) were positively and significantly related to logTSH. Women taking additional Se/Zn/Cu supplements were 1·46 (95 % CI 1·09, 2·04) times less likely to have elevated titres of TPO-Ab at 12 weeks of gestation. We conclude that first-trimester Se reference ranges are influenced by Se-supplement intake, while Cu and Zn ranges are not. Plasma mineral Se/Zn/Cu concentrations are associated with thyroid FT4 and TSH concentrations. Se/Zn/Cu supplement intake affects TPO-Ab status. Future research should focus on the impact of trace mineral status during gestation on thyroid function.

In the isolation of polymorphonuclear neutrophils (PMNs) the technique and other external factors can have great influence on the quality and quantity of isolated neutrophils. To elucidate the influence of the blood collection technique, anticoagulants and storing temperature on isolated PMNs healthy volunteers provided blood samples with different needles and collection techniques, anticoagulants (EDTA, heparin, citrate) and storing temperatures (4, 22, 37 °C). From each blood sample PMNs were isolated and compared regarding number of PMNs and oxidative burst. The blood collection technique, anticoagulants and storing temperature had minor impact on isolated PMNs. All three tested cannulas and anticoagulants can be used to obtain blood samples for PMN isolation. For storing temperatures 37 °C should be preferred. Regarding time between the PMN isolation and the actual experiments, a time span of maximum 1 h should be targeted.

Argon exerts neuroprotection. Thus, it might improve patients' neurological outcome after cerebral disorders or cardiopulmonary resuscitation. However, limited data are available concerning its effect on pulmonary vessel and airways. We used rat isolated perfused lungs (IPL) and precision-cut lung slices (PCLS) of rats and humans to assess this topic. IPL: Airway and perfusion parameters, oedema formation and the pulmonary capillary pressure (P cap ) were measured and the precapillary and postcapillary resistance (R post ) was calculated. In IPLs and PCLS, the pulmonary vessel tone was enhanced with ET-1 or remained unchanged. IPLs were ventilated and PCLS were gassed with argon-mixture or room-air. IPL: Argon reduced the ET-1-induced increase of P cap , R post and oedema formation (p < 0.05). PCLS (rat): Argon relaxed naïve pulmonary arteries (PAs) (p < 0.05). PCLS (rat/human): Argon attenuated the ET-1-induced contraction in PAs (p < 0.05). Inhibition of GABA B -receptors abolished argon-induced relaxation (p < 0.05) in naïve or ET-1-pre-contracted PAs; whereas inhibition of GABA A -receptors only affected ET-1-pre-contracted PAs (p < 0.01). GABA A/B -receptor agonists attenuated ET-1-induced contraction in PAs and baclofen (GABA B -agonist) even in pulmonary veins (p < 0.001). PLCS (rat): Argon did not affect the airways. Finally, argon decreases the pulmonary vessel tone by activation of GABA-receptors. Hence, argon might be applicable in patients with pulmonary hypertension and right ventricular failure.

An asymptomatic systemic inflammation after exposure to zinc- and copper-containing welding fumes has been described as mild form of metal fume fever in recent studies. Since chronic systemic inflammation leads to a higher cardiovascular risk, examining the inflammation with the underlying pathomechanism is necessary to estimate and hopefully prevent long-term effects of welding. We established a whole blood assay to investigate the effects of zinc- and copper-containing welding fume particles on the blood immune response. Increased levels of IL-6, IL-8, TNFα and IL-1β determined after 24 hours of exposure indicated an acute systemic inflammatory reaction. In vitro increases of IL-6 were comparable to in vivo increases of serum IL-6 levels in a study with welding fume exposure of human subjects. Inhibition of PTP1B was identified as one pathway responsible for the effects of zinc- and copper-containing welding fumes and therefore welding fume fever. In conclusion, the whole blood assay is a reliable and feasible method to investigate effects of zinc- and copper-containing welding fumes on the immune system and as a surrogate for systemic inflammation and welding fume fever. Future research can utilize whole blood assays to reduce and partially replace human exposure studies for further investigations of welding fume fever.

Recently, side effects of plasma expanders like hydroxyethyl starch and gelatine gained considerable attention. Most studies have focused on the kidneys; lungs remain unconsidered. Isolated mouse lungs were perfused for 4 hours with buffer solutions based on hydroxyethyl starch (HES) 130/0.4, HES 200/0.5 or gelatine and ventilated with low or high pressure under physiological pH and alkalosis. Outcome parameters were cytokine levels and the wet-to-dry ratio. For cytokine release, murine and human PCLS were incubated in three different buffers and time points.In lungs perfused with the gelatine based buffer IL-6, MIP-2 and KC increased when ventilated with high pressure. Wet-to-dry ratios increased stronger in lungs perfused with gelatine - compared to HES 130/0.4. Alkalotic perfusion resulted in higher cytokine levels but normal wet-to-dry ratio. Murine PCLS supernatants showed increased IL-6 and KC when incubated in gelatine based buffer, whereas in human PCLS IL-8 was elevated. In murine IPL HES 130/0.4 has lung protective effects in comparison to gelatine based infusion solutions, especially in the presence of high-pressure ventilation. Gelatine perfusion resulted in increased cytokine production. Our findings suggest that gelatine based solutions may have side effects in patients with lung injury or lung oedema.

Background: The family of Ustilaginaceae is known for their capability to naturally produce industrially valuable chemicals from different carbon sources. Recently, several Ustilaginaceae were reported to produce organic acids from glycerol, which is the main side stream in biodiesel production., Results: In this study, we present Ustilago   vetiveriae as new production organism for itaconate synthesis from glycerol. In a screening of 126 Ustilaginaceae, this organism reached one of the highest titers for itaconate combined with a high-glycerol uptake rate. By adaptive laboratory evolution, the production characteristics of this strain could be improved. Further medium optimization with the best single colony, U.   vetiveriae  TZ1, in 24-deep well plates resulted in a maximal itaconate titer of 34.7 ± 2.5 g L -1 produced at a rate of 0.09 ± 0.01 g L -1  h -1 from 196 g L -1 glycerol. Simultaneously, this strain produced 46.2 ± 1.4 g L -1 malate at a rate of 0.12 ± 0.00 g L -1  h -1 . Due to product inhibition, the itaconate titer in NaOH-titrated bioreactor cultivations was lower (24 g L -1 ). Notably, an acidic pH value of 5.5 resulted in decreased itaconate production, however, completely abolishing malate production. Overexpression of ria1 or mtt1 , encoding a transcriptional regulator and mitochondrial transporter, respectively, from the itaconate cluster of U.   maydis resulted in a 2.0-fold ( ria1) and 1.5-fold ( mtt1 ) higher itaconate titer in comparison to the wild-type strain, simultaneously reducing malate production by 75 and 41%, respectively., Conclusions: The observed production properties of U.   vetiveriae  TZ1 make this strain a promising candidate for microbial itaconate production. The outcome of the overexpression experiments, which resulted in reduced malate production in favor of an increased itaconate titer, clearly strengthens its potential for industrial itaconate production from glycerol as major side stream of biodiesel production.