Evaluation and Comparison of Relaxation-Related Workplace Interventions Among Office Workers at an Insurance Institution: An Intervention Study.

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.

Adjuvant Gemcitabine Versus Neoadjuvant/Adjuvant FOLFIRINOX in Resectable Pancreatic Cancer: The Randomized Multicenter Phase II NEPAFOX Trial.

BACKGROUND: Although addition of adjuvant chemotherapy is the current standard, the prognosis of pancreatic cancers still remains poor. The NEPAFOX trial evaluated perioperative treatment with FOLFIRINOX in resectable pancreatic cancer. PATIENTS AND METHODS: This multicenter phase II trial randomized patients with resectable or borderline resectable pancreatic cancer without metastases into arm (A,) upfront surgery plus adjuvant gemcitabine, or arm (B,) perioperative FOLFIRINOX. The primary endpoint was overall survival (OS). RESULTS: Owing to poor accrual, recruitment was prematurely stopped after randomization of 40 of the planned 126 patients (A: 21, B: 19). Overall, approximately three-quarters were classified as primarily resectable (A: 16, B: 15), and the remaining patients were classified as borderline resectable (A: 5, B: 4). Of the 12 evaluable patients, 3 achieved partial response under neoadjuvant FOLFIRINOX. Of the 21 patients in arm A and 19 patients in arm B, 17 and 7 underwent curative surgery, and R0-resection was achieved in 77% and 71%, respectively. Perioperative morbidity occurred in 72% in arm A and 46% in arm B, whereas non-surgical toxicity was comparable in both arms. Median RFS/PFS was almost doubled in arm B (14.1 months) compared with arm A (8.4 months) in the population with surgical resection, whereas median OS was comparable between both arms. CONCLUSIONS: Although the analysis was only descriptive owing to small patient numbers, no safety issues regarding surgical complications were observed in the perioperative FOLFIRINOX arm. Thus, considering the small number of patients, perioperative treatment approach appears feasible and potentially effective in well-selected cohorts of patients. In pancreatic cancer, patient selection before initiation of neoadjuvant therapy appears to be critical.

Lung cancer risk and occupational pulmonary fibrosis: systematic review and meta-analysis.

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.

Occupational exposure to polychlorinated biphenyls: Development of neuropsychological functions over time.

Occupational exposure to polychlorinated biphenyls (PCBs) continues to affect the health of exposed individuals until today. This study aims to expand previous findings by examining the development of neuropsychological functions of occupationally exposed participants over time. Especially verbal fluency and sensorimotor processing, found to be impaired in a previous study, were thus of particular interest. A total of 116 participants, who were part of the HELPcB cohort, underwent a neuropsychological test battery covering a multitude of cognitive functions. Plasma PCB levels were determined for each participant and classified as elevated or normal based on comparative values drawn from the German general population. Two structural equation models were then used to examine the effects of elevated PCB levels on neuropsychological functions. Results suggest that participants who displayed increased PCB plasma levels continued to show impairments in verbal fluency but not in sensorimotor processing after a second examination one year after the first measurement. Specifically, low chlorinated PCBs are associated with impaired verbal fluency, as compared to high-chlorinated and dioxin-like congeners. Alteration of dopamine concentration in response to PCB exposure might be a potential explanation of this result.

Nutrimetric Validation of Solanidine as Dietary-Derived CYP2D6 Activity Marker In Vivo.

CYP2D6 is involved in the metabolism of many drugs. Its activity is affected by pharmacogenetic variability leading to highly polymorphic phenotypes between individuals, affecting safety and efficacy of drugs. Recently, solanidine, a steroidal alkaloid from potatoes, and its metabolites, has been identified as a dietary-derived activity marker for CYP2D6. The intraday variability in plasma within individuals has not been studied yet in healthy subjects. As part of a CYP phenotyping cocktail study with 20 healthy participants, plasma concentrations of solanidine, 4-OH-solanidine and 3,4-secosolanidine-3,4-dioic acid (SSDA) were determined using a sensitive liquid chromatography-mass spectrometry method in urine and in plasma at timepoints 0, 2.5, 5, 8, and 24 hours after intake of test substances. The participants were phenotyped for CYP2D6 with oral metoprolol (12.5 mg) with 15 plasma sampling points over 24 hours (DRKS00028922). Metabolic ratios (MRs) of metabolite to parent plasma concentrations were formed from single timepoints and the area under the curve (AUC). All participants were genotyped for CYP2D6. The intra-individual variability of the CYP2D6 metabolite SSDA was highly stable with a median SD of 11.62% over 24 hours. MR SSDA/solanidine was more variable (median SD 31.90%) but correlated significantly at all measured timepoints with AUC MR α-OH-metoprolol/metoprolol. The AUC MR SSDA/solanidine showed a significant linear relationship with the genetically predicted CYP2D6 activity score. This study substantiates the MR SSDA/solanidine as CYP2D6 activity marker. The high correlation with metoprolol MR indicates a valid prediction of the CYP2D6 phenotype at any timepoint during the study day.

Evaluation of a Workplace Active Rest Program in Office Workers With Comparison of a Prospective and Retrospective Survey.

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 (npre = 405, npost = 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.

The role of the DC component in human perception of AC-DC hybrid electric fields and a comparison with the AC component.

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.

Ten years after: findings from the medical surveillance program on Health Effects in High-Level Exposure to PCB (HELPcB).

After the detection of high environmental and occupational exposure to polychlorinated biphenyls (PCBs) in a German recycling company for transformers and capacitors in 2010, the multidisciplinary medical surveillance program "HELPcB" (Health Effects in High-Level Exposure to PCB) was established for former PCB-exposed workers of the company, their family members, employees of surrounding companies, and area residents to investigate potential adverse health effects by PCB exposure in a longitudinal study approach with up to seven examination time points between 2010 and 2019. More than 300 individuals were enrolled into the program. Assessments particularly included plasma and urine concentrations of PCB congeners and their metabolites, clinical laboratory parameters, Comet assay, analysis of telomere length, neuropsychological examinations, psychological screening, abdominal and thyroid ultrasound examination. This review summarizes the main results of the studies conducted in the HELPcB program yielding relevant new data on potential adverse effects of PCB exposure in humans and potential mechanisms that underlie these effects. Even larger studies in PCB-exposed individuals are warranted to confirm the results of this program and to further establish causality between PCB exposure and clinical effects in humans.

[Health protection and climate change require ambitious limit values for air pollutants in Europe : Opinion on the revision of the Directive on Air Quality and Clean Air for Europe of the Environmental Public Health commission of the Robert Koch Institute and the Federal Environment Agency]. / Gesundheitsschutz und Klimawandel erfordern ambitionierte Grenzwerte für Luftschadstoffe in Europa : Stellungnahme zur Revision der Richtlinie über Luftqualität und saubere Luft für Europa der Kommission Environmental Public Health des Robert Koch-Instituts und des Umweltbundesamtes.

Based on scientific findings, the World Health Organization (WHO) has recommended stricter guideline values for air quality in 2021. Significant reductions in the annual mean values of particulate matter (particle size 2.5 µm or smaller, PM2.5) and long-term exposure to nitrogen dioxide (NO2) and ozone (O3) were put forward. The risk of mortality already increases above the WHO guideline values, as shown in studies investigating low concentrations of air pollutants. In Germany, the 2021 WHO guideline values for PM2.5 and NO2 were clearly exceeded in 2022.In this position paper we give the following recommendations for the European Air Quality Directive: (1) set binding limit values according to WHO 2021, (2) apply the limit values to the whole of Europe, (3) continue and expand the established country-based monitoring networks, (4) expand air quality measurements for ultrafine particles and soot particles, and (5) link air pollution control and climate protection measures.Stricter limits for air pollutants require societal and political changes in areas such as mobility, energy use and generation, and urban and spatial planning. Implementation according to WHO 2021 would lead to a net economic benefit of 38 billion euros per year.Ambitious limit values for air pollutants also have an impact on climate change mitigation and its health impacts. The Environmental Public Health commission concludes that more ambitious limit values are crucial to enable effective health protection in Germany and calls for air pollutant limit values in line with the 2021 WHO recommendations to become binding in Europe.

Effects of repetition as training and incentives on the performance in pulmonary function tests in healthy volunteers.

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.

Self-Reported Pre-Pandemic Physical Activity and Likelihood of COVID-19 Infection: Data from the First Wave of the CoCo-Fakt Survey.

OBJECTIVES: To investigate the potential protective role of exercise on the odds of COVID-19 infection in unvaccinated contact persons (CPs) who were at higher risk of infection due to confirmed contact with infected persons. METHODS: Before the onset of the vaccination campaign, the first wave of the CoCo-Fakt online survey was conducted with SARS-CoV-2-positive persons and their confirmed contacts who were isolated/quarantined between 1 March 2020 and 9 December 2020. Within this analysis, 5338 CPs were included and divided into those who subsequently tested positive (CP-P) and those who remained negative (CP-N). We assessed demographics as well as pre-pandemic lifestyle characteristics including physical activity (PA; type, frequency, time, intensity; duration clustered as 'below PA guidelines', 'meeting PA guidelines', and 'above PA guidelines'; intensity clustered as 'low intensity' and 'moderate-to-vigorous intensity') and sedentary behaviour. RESULTS: A greater percentage of CP-Ns reported being active before the pandemic compared to CP-Ps (69% vs. 63%; p = .004). Moreover, CP-Ns reported higher PA duration (164.1 min/week vs. 143.2 min/week; p = .038) and higher PA intensities than CP-Ps (67% vs. 60% moderate-to-vigorous intensity, 33% vs. 40% low intensity; p = .003). Adjusting for age, sex, socioeconomic status, migration background, and pre-existing chronic diseases, the odds of infection were negatively associated with exercise (yes/no) (Nagelkerke R2 = 1.9%), PA levels above PA guidelines (Nagelkerke R2 = 2.0%), and PA intensity (Nagelkerke R2 = 1.8%). CONCLUSION: Due to the beneficial effects of PA on the odds of infection, an active lifestyle should be promoted especially during possible subsequent pandemics (while taking into account necessary hygiene measures). Moreover, inactive and chronically ill persons should be especially encouraged to adopt a healthier lifestyle.

Short-term exposure to zinc- and copper-containing welding fumes: Effects on pulmonary function in humans.

Zinc- and copper-containing welding fumes typically induce a systemic inflammation indicated by increase in C-reactive protein (CRP) levels, also known as welding fume fever. It typically includes symptoms like fever, myalgia or headaches, but only a quarter of patients experience respiratory symptoms, e.g. coughing. This retrospective analysis of data of three studies with either control (filtered air) or zinc- and copper-containing welding fume exposure aims to identify and characterize the effect of the welding fumes on lung function. Spirometry and body plethysmography data of male healthy volunteers were analyzed and comparisons between different timepoints after a 6 h exposure were conducted. For controls no significant changes in spirometry were observed between baseline and 6 h, 24 h and 1 week after exposure. For volunteers exposed to zinc- and copper-containing welding fumes no significant reductions in forced expiratory volume in 1 s (FEV1) and minimal reductions in vital capacity (VC) (52 ml, 0.9%) were detected after 6 h. After 24 h significant reductions in FEV1 (147 ml, 3.2%) and VC (162 ml, 2.9%) could be observed. 1 week after exposure FEV1 was still significantly reduced (102 ml, 2.1%) and airway resistance were increased while no differences in VC were detected. The reduction of FEV1% after 24 week significantly correlated with increases in CRP levels. In conclusion, a single exposure to zinc- and copper-containing welding fumes leads not only to a systemic inflammation but could also induce slight sustained airway constrictions after 24 h and 1 week. The observed slight airway constriction is not caused by immediate effects but possibly inflammatory processes. Although welding fume fever does not necessarily present respiratory symptoms, welders exposed to zinc- and copper-containing welding fumes should be monitored for respiratory symptoms and obstructive ventilation pattern.

Quantification of 26 metals in human urine samples using ICP-MSMS in a random sample collective of an occupational and environmental health care center in Aachen, Germany.

Despite several studies on metal exposure in the general population, the knowledge on the background burden of distinct metals is still sparse (e.g. Cu, In, Mn, Pb, Sn, Sr, Ta, Te). While up to date reference values exist for 16 distinct metals as Biological Reference Value (BAR) or the 95th percentile for Al, As, Ba, Be, Cd, Co, Cr, Hg, Li, Mo, Ni, Pt, Sb, Se, Tl and U respectively, the background burden of the general population for the remaining elements is unknown or yet no matter of scientific counselling. We established and validated an inductively coupled plasma triple quadrupole mass spectrometry (ICP-MSMS) human biomonitoring method (HBM), that enabled us to determine 26 metals in urine. Al, As, Ba, Be, Cd, Co, Cu, Ga, Gd, Hg, In, Li, Mo, Ni, Pb, Sb, Se, Sn, Sr, Ta, Te, Tl, V and Zn were analyzed. The method was applied to 88 urine samples collected in the ambulance of the Institute for Occupational, Social and Environmental Medicine (IASU) Aachen, Germany. Patients from two major metal processing companies (steel and copper) and a more heterogenous group of occupational exposed and non-exposed persons were defined and distinguished. HBM data from about 88, in general occupationally unexposed persons against certain metals served as a collective representing the general population in first approximation. For these the 95th percentiles are reported. Significant differences of urinary metal concentrations of the employees of the two metal processing companies compared to the third group were observed among others for Cu, Cr, Ni, Mn and are discussed, thus demonstrating the usefulness of the method for both environmental and occupational purposes.

Blood lead monitoring in a former mining area in Euskirchen, Germany: results of a representative random sample in 3- to 17-year-old children and minors.

Heavy metal residues in former mining areas can pose a burden to the local environment and population even decades after closure of the mining sites. In the North Rhine-Westphalian (Germany) communities of Mechernich and Kall, both parts of the district of Euskirchen, lead residues are a source of health concerns for local residents. A statistically representative collective of both communities depending on sex, age, and area of residence was created, mirroring the local underage population. The blood lead levels (BLL) of 182 children and minors in the two adjacent communities were assessed via ICP-MSMS. The results were compared to German lead reference values, valid for the general underage population. In total, 32 (17.6%) of the subjects investigated exceeded the according reference values of 15 µg/L and 20 µg/L, respectively, depending on sex and age, thus pointing out an additional lead burden affecting children in the area. Potential lead sources contributing to the BLL were evaluated using a questionnaire. Factors that showed significant impact on the BLL were, other than age, sex, height, and weight, the factors occupancy, time spend in the garden, garden hand-to-mouth contact, consumption frequency of homegrown products, and lifestyle factors. The data presented enable both residents and the local authorities to further reduce lead exposure and to take appropriate personal and public action.

Risk Factor Identification for Delayed Gastric Emptying after Distal Pancreatectomy-An Evaluation of 1688 Patients Based on the German StuDoQ|Pancreas Registry.

Delayed gastric emptying (DGE) ranks as one of the most frequent complications in pancreatic surgery. It leads to increased costs for healthcare systems, lengthened hospital stays and reduced quality of life. Data about DGE after distal pancreatectomy (DP) are scarce. The StuDoQ|Pancreas registry of the German Society of General and Visceral Surgery provided data of patients who underwent distal pancreatectomy from 1 January 2014 to 31 December 2018. The retrospective evaluation included comprehensive data: 1688 patients were enrolled; DGE occurred 160 times (9.5%); grade "A" was reported for 98 (61.3%), grade "B" for 41 (25.6%) and grade "C" for 21 (13.1%) patients. In univariate analysis pancreatic fistulas were associated with higher frequencies of intraabdominal abscesses (9.1% vs. 2%, p > 0.001), postpancreatectomy haemorrhage (8.1% vs. 3.7%, >0.001) and DGE (14.5% vs. 6%, p < 0.001). According to multivariate analysis, "abscesses with invasive therapy" (p < 0.001), "other surgical complications" (p < 0.001), prolonged "stays in ICU" (p < 0.001), lengthened duration of surgery (p < 0.001) and conventional surgery (p = 0.007) were identified as independent risk factors for DGE. Perioperative and postoperative factors were identified as risk factors for DGE. Following research should examine this highly relevant topic in a prospective, register-based manner. As there is no causal therapy for DGE, its avoidance is of major importance.

The human long noncoding RNAs CoroMarker, MALAT1, CDR1as, and LINC00460 in whole blood of individuals after controlled short-term exposure with ultrafine metal fume particles at workplace conditions, and in human macrophages in vitro.

BACKGROUND: Short-term inhalation of occupationally relevant ultrafine zinc/copper (Zn/Cu) containing welding fumes has been shown to induce subclinical systemic inflammation, associated with an elevated risk for cardiovascular diseases. The involvement of noncoding RNAs (lncRNAs) in this setting is currently unknown. However, lncRNAs have been reported to fulfill essential roles in, e.g., cardiovascular diseases, inflammation, infectious diseases, and pollution-related lung disorders. METHODS: In this study, the specific lncRNAs levels of the 4 lncRNAs CoroMarker, MALAT1, CDR1as and LINC00460 were determined by RT-qPCR in THP-1 macrophages exposed to Zn/Cu metal fume suspensions for 1, 2, and 4 hours in vitro. Furthermore, 14 subjects were exposed to Zn/Cu containing welding fumes (at 2.5 mg/m3) for 6 hours. Before, 6, 10, and 29 hours after exposure start, whole blood cell lncRNAs levels were determined by RT-qPCR. RESULTS: In THP-1 macrophages, we observed a 2.3-fold increase of CDR1as at 1 h (Wilcoxon p = 0.03), a non-significant increase of CoroMarker at 1 h, and an increase of LINC00460 at 2 h (p = 0.03) and at 4 h (p = 0.06). In whole blood cells, we determined a non-significant upregulation of CDR1as at 6 h (p = 0.2), a significant downregulation of CoroMarker at 6 h (p = 0.04), and a significant upregulation of LINC00460 levels at 10 h (p = 0.04) and 29 h (p = 0.04). MALAT-1 remained unchanged in both settings. CONCLUSION: The orientation of regulation of the lncRNAs is (except for CoroMarker) similar in the in vitro and in vivo experiments and in line with their described functions. Therefore, these results, e.g. the upregulation of the potential risk marker for cardiovascular diseases, CDR1as, contribute to understanding the underlying mechanisms of Zn/Cu-induced subclinical inflammation in metal workers.

Discovery and intranasal administration of a SARS-CoV-2 broadly acting neutralizing antibody with activity against multiple Omicron subvariants.

BACKGROUND: The continual emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern, in particular the newly emerged Omicron (B.1.1.529) variant and its BA.X lineages, has rendered ineffective a number of previously FDA emergency use authorized SARS-CoV-2 neutralizing antibody therapies. Furthermore, those approved antibodies with neutralizing activity against Omicron BA.1 are reportedly ineffective against the subset of Omicron subvariants that contain a R346K substitution, BA.1.1, and the more recently emergent BA.2, demonstrating the continued need for discovery and characterization of candidate therapeutic antibodies with the breadth and potency of neutralizing activity required to treat newly diagnosed COVID-19 linked to recently emerged variants of concern. METHODS: Following a campaign of antibody discovery based on the vaccination of Harbor H2L2 mice with defined SARS-CoV-2 spike domains, we have characterized the activity of a large collection of spike-binding antibodies and identified a lead neutralizing human IgG1 LALA antibody, STI-9167. FINDINGS: STI-9167 has potent, broad-spectrum neutralizing activity against the current SARS-COV-2 variants of concern and retained activity against each of the tested Omicron subvariants in both pseudotype and live virus neutralization assays. Furthermore, STI-9167 nAb administered intranasally or intravenously provided protection against weight loss and reduced virus lung titers to levels below the limit of quantitation in Omicron-infected K18-hACE2 transgenic mice. CONCLUSIONS: With this established activity profile, a cGMP cell line has been developed and used to produce cGMP drug product intended for intravenous or intranasal use in human clinical trials. FUNDING: Funded by CRIPT (no. 75N93021R00014), DARPA (HR0011-19-2-0020), and NCI Seronet (U54CA260560).

Environmental release of non-Aroclor polychlorinated biphenyls by a silicone rubber production site did not lead to elevated plasma levels in the nearby population.

In 2019, high concentrations of the non-Aroclor PCB congeners 47, 51, and 68 were released by a silicone rubber production site in North-Rhine Westphalia, Germany. Local authorities announced a consumption alert for home-grown fruits and vegetables for the affected area which led to a great level of insecurity among the population regarding potential health effects. The aim of study was to determine the plasma levels of the non-Aroclor congeners and the six ndl-indicator congeners (PCB 28, 52, 101, 138, 153, 180) in children and women with child-bearing potential living close to the production site. Altogether n = 111 participants, with n = 73 female adults and n = 38 children were included in this analysis. For the non-Aroclor-PCBs as well as the lower-clorinated ndl-indicator PCBs 28, 52, and 101, the median plasma concentrations were below the LOQ. Only one adult showed an elevated PCB 47 value. In conclusion, no elevated plasma levels could be detected for PCB 47, 51, or 68 in the nearby population of the silicone-rubber production site. However, our study was highly important for risk characterisation as well as risk communication.