Discovery of IRAK4 Inhibitors BAY1834845 (Zabedosertib) and BAY1830839.

Interleukin-1 receptor-associated kinase 4 (IRAK4) plays a critical role in innate inflammatory processes. Here, we describe the discovery of two clinical candidate IRAK4 inhibitors, BAY1834845 (zabedosertib) and BAY1830839, starting from a high-throughput screening hit derived from Bayer's compound library. By exploiting binding site features distinct to IRAK4 using an in-house docking model, liabilities of the original hit could surprisingly be overcome to confer both candidates with a unique combination of good potency and selectivity. Favorable DMPK profiles and activity in animal inflammation models led to the selection of these two compounds for clinical development in patients.

Neurophysiological signatures of sensory-processing sensitivity.

Background: Sensory processing sensitivity is mainly captured based on questionnaires and it's neurophysiological basis is largely unknown. As hitherto no electroencephalography (EEG) study has been carried out, the aim of this work was to determine whether the self-reported level of SPS correlates with the EEG activity in different frequency bands. Methods: One hundred fifteen participants were measured with 64-channel EEG during a task-free resting state. After artifact correction, a power spectrum time series was calculated using the Fast Fourier Transform (FFT) for the following frequency bands: Delta: 1-3.5 Hz, theta: 4-7.5 Hz, alpha1: 8-10 Hz, alpha2: 10.5-12 Hz, beta1: 12.5-15 Hz, beta2: 15.5-25 Hz, gamma: 25.5-45 Hz, global: 1-45 Hz. Correlations with the 'Highly Sensitive Person Scale' (HSPS-G) scores were determined. Then, the lowest and the highest 30% of the cohort were contrasted as polar opposites. EEG features were compared between the two groups applying a paired two-tailed t-test. Results: The HSPS-G scores correlated statistically significantly positive with beta 1 and 2, and global EEG power during resting with eyes open, but not during resting with eyes closed. The highly sensitive group revealed higher beta power (4.38 ± 0.32 vs. 4.21 ± 0.17, p = 0.014), higher gamma power (4.21 ± 0.37 vs. 4.00 ± 0.25, p = 0.010), and increased global EEG power (4.38 ± 0.29 vs. 4.25 ± 0.17, p = 0.041). The higher EEG activity in the HSP group was most pronounced in the central, parietal, and temporal region, whereas lower EEG activity was most present in occipital areas. Conclusion: For the first time, neurophysiological signatures associated with SPS during a task free resting state were demonstrated. Evidence is provided that neural processes differ between HSP and non-HSP. During resting with eyes open HSP exhibit higher EEG activity suggesting increased information processing. The findings could be of importance for the development of biomarkers for clinical diagnostics and intervention efficacy evaluation.

Sensory-Processing Sensitivity Is Associated with Increased Neural Entropy.

BACKGROUND: This study aimed at answering the following research questions: (1) Does the self-reported level of sensory-processing sensitivity (SPS) correlate with complexity, or criticality features of the electroencephalogram (EEG)? (2) Are there significant EEG differences comparing individuals with high and low levels of SPS? METHODS: One hundred fifteen participants were measured with 64-channel EEG during a task-free resting state. The data were analyzed using criticality theory tools (detrended fluctuation analysis, neuronal avalanche analysis) and complexity measures (sample entropy, Higuchi's fractal dimension). Correlations with the 'Highly Sensitive Person Scale' (HSPS-G) scores were determined. Then, the cohort's lowest and the highest 30% were contrasted as opposites. EEG features were compared between the two groups by applying a Wilcoxon signed-rank test. RESULTS: During resting with eyes open, HSPS-G scores correlated significantly positively with the sample entropy and Higuchi's fractal dimension (Spearman's ρ = 0.22, p < 0.05). The highly sensitive group revealed higher sample entropy values (1.83 ± 0.10 vs. 1.77 ± 0.13, p = 0.031). The increased sample entropy in the highly sensitive group was most pronounced in the central, temporal, and parietal regions. CONCLUSION: For the first time, neurophysiological complexity features associated with SPS during a task-free resting state were demonstrated. Evidence is provided that neural processes differ between low- and highly-sensitive persons, whereby the latter displayed increased neural entropy. The findings support the central theoretical assumption of enhanced information processing and could be important for developing biomarkers for clinical diagnostics.

Effects of Housing Vouchers on the Long-Term Exposure to Neighborhood Opportunity among Low-Income Families: The Moving to Opportunity Experiment.

Tenant-based rental assistance has received much attention as a tool to ameliorate American poverty and income segregation. We examined whether a tenant-based voucher program improves long-term exposure to neighborhood opportunity overall and across multiple domains-social/economic, educational, and health/environmental-among low-income families with children. We used data from the Moving to Opportunity (MTO) experiment (1994-2010) with a 10- to 15-year follow-up period and used an innovative and multidimensional measure of neighborhood opportunities for children. Compared with controls in public housing, MTO voucher recipients experienced improvement in neighborhood opportunity overall and across domains during the entire study period, with a larger treatment effect for families in the MTO voucher group who received supplementary housing counseling, than the Section 8 voucher group. Our results also suggests that effects of housing vouchers on neighborhood opportunity may not be uniform across subgroups. Results from model-based recursive partitioning for neighborhood opportunity identified several potential effect modifiers for housing vouchers, including study sites, health and developmental problems of household members, and having vehicle access.

Efficacy of COVID-19 Booster Vaccines in Patients with Hematologic Malignancies: Experiences in a Real-World Scenario.

Background: Two-dose COVID-19 vaccination often results in poor humoral response rates in patients with hematologic malignancies (HMs); yet responses to COVID-19 booster vaccines and the risk of COVID-19 infection post-booster are mostly uncertain. Methods: We included 200 outpatients with HMs and predominantly lymphoid neoplasms (96%, 191/200) in our academic center and reported on the humoral responses, which were assessed by measurement of anti-spike IgG antibodies in peripheral blood as early as 14 days after mRNA-based prime-boost vaccination, as well as factors hampering booster efficacy. Previous basic (double) immunization was applied according to the local recommendations with mRNA- and/or vector-based vaccines. We also report on post-booster COVID-19 breakthrough infections that emerged in the Omicron era and the prophylaxis strategies that were applied to poor and non-responders to booster vaccines. Results: A total of 55% (110/200) of the patients achieved seroconversion (i.e., anti-spike protein IgG antibody titer > 100 AU/mL assessed in median 48 days after prime-boost vaccination) after prime-boost vaccination. Multivariable analyses revealed age, lymphocytopenia, ongoing treatment and prior anti-CD20 B-cell depletion to be independent predictors for booster failure. With each month between anti-CD20-mediated B-cell depletion and booster vaccination, the probability of seroconversion increased by approximately 4% (p < 0.001) and serum−antibody titer (S-AbT) levels increased by 90 AU/mL (p = 0.011). Notably, obinutuzumab treatment was associated with an 85% lower probability for seroconversion after prime-boost vaccination compared to rituximab (p = 0.002). Of poor or non-responders to prime-boost vaccination, 41% (47/114) underwent a second booster and 73% (83/114) underwent passive immunization. COVID-19 breakthrough infections were observed in 15% (29/200) of patients after prime-boost vaccination with predominantly mild courses (93%). Next to seroconversion, passive immunization was associated with a significantly lower risk of COVID-19 breakthrough infections after booster, even in vaccine non-responders (all p < 0.05). In a small proportion of analyzed patients with myeloid neoplasms (9/200), the seroconversion rate was higher compared to those with lymphoid ones (78% vs. 54%, accordingly), while the incidence rate of COVID-19 breakthrough infections was similar (22% vs. 14%, respectively). Following the low frequency of myeloid neoplasms in this study, the results may not be automatically applied to a larger cohort. Conclusions: Patients with HMs are at a high risk of COVID-19 booster vaccine failure; yet COVID-19 breakthrough infections after prime-boost vaccination are predominantly mild. Booster failure can likely be overcome by passive immunization, thereby providing immune protection against COVID-19 and attenuating the severity of COVID-19 courses. Further sophistication of clinical algorithms for preventing post-vaccination COVID-19 breakthrough infections is urgently needed.

Temporal trends of mercury levels in fish (dab, Limanda limanda) and sediment from the German Bight (North Sea) in the period 1995-2020.

As a toxic and harmful global pollutant, mercury (Hg) enters the marine environment through natural sources, and human activities. It bioaccumulates through the food chain and therefore, Hg is of great importance for environmental monitoring. This study aims to answer the question if Hg contamination in fish and sediment from the German Bight follows temporal trends. Therefore, 496 individual female dab (Limanda limanda) were analyzed. The Hg concentrations in the muscle of dab from the German Bight showed significant increase in function of time with an annual percental change of 1.4%, leading to a 41% increase in Hg contamination level within 25 years of monitoring. At the same time, Hg concentrations in sediment-analyzed in 86 samples-significantly decreased in the nearby North Sea environment. This surprising contradiction is shown in the present study and possible causes are discussed. It could be clearly shown that contamination in sediment and biota can follow completely different time courses and therefore, different environmental matrices should be considered in future monitoring studies. Age of the fish turned out to be a biological factor of particular importance for temporal trend analysis.

Do Alcohol Outlets Mediate the Effects of the Moving to Opportunity Experiment on Adolescent Excessive Drinking? A Secondary Analysis of a Randomized Controlled Trial.

Background: Housing mobility impacts adolescent alcohol use, and the neighborhood built environment may impact this relationship. Methods: Moving to Opportunity (MTO) was a multi-site, three-arm, household-level experiment. MTO randomly assigned one of three treatment arms (1994-1997) allowing families living in public housing to (1) receive a voucher to be redeemed any neighborhood (2) receive a voucher to be redeemed in a neighborhood with less than 10% poverty (3) remain in public housing (control). MTO decreased girls' alcohol use, but increased boys' alcohol use. Treatment groups were pooled because they are similar conceptually and statistically on our primary outcome. Among youth aged 12-19 in 2001-2002 (N = 2829), we estimated controlled direct effects mediation of MTO treatment effects on youth with housing vouchers (N = 1950) vs. controls (N = 879) on past 30-day number of drinks per day on days drank, using gender-stratified Poisson regression. Mediators were density of on- and off-premises alcohol outlets per square mile at the families' census tract of residence in 1997. Results: Treatment group youth were randomized to live in 1997 census tracts with lower off-premises, but higher on-premises, outlet density. MTO treatment (vs. controls) decreased drinking for girls via alcohol outlet density, but only at higher levels of outlet density. Treatment was 18% more beneficial when girls moved to high density neighborhoods, compared to controls who stayed living in public housing in high density neighborhoods. Conclusion: Additional social processes unmeasured in the current study may play an important role in the alcohol use and other health risks for girls.

Housing mobility protects against alcohol use for children with socioemotional health vulnerabilities: An experimental design.

PURPOSE: Neighborhood context may influence alcohol use, but effects may be heterogeneous, and prior evidence is threatened by confounding. We leveraged a housing voucher experiment to test whether housing vouchers' effects on alcohol use differed for families of children with and without socioemotional health or socioeconomic vulnerabilities. TRIAL DESIGN: In the Moving to Opportunity (MTO) study, low-income families in public housing in five US cities were randomized in 1994 to 1998 to receive one of three treatments: (1) a housing voucher redeemable in a low-poverty neighborhood plus housing counseling, (2) a housing voucher without locational restriction, or (3) no voucher (control). Alcohol use was assessed 10 to 15 years later (2008 to 2010) in youth ages 13 to 20, N = 4600, and their mothers, N = 3200. METHODS: Using intention-to-treat covariate-adjusted regression models, we interacted MTO treatment with baseline socioemotional health vulnerabilities, testing modifiers of treatment on alcohol use. RESULTS: We found treatment effect modification by socioemotional factors. For youth, MTO voucher treatment, compared with controls, reduced the odds of ever drinking alcohol if youth had behavior problems (OR = 0.26, 95% CI [0.09, 0.72]) or problems at school (OR = 0.46, [0.26, 0.82]). MTO low-poverty treatment (vs. controls) also reduced the number of drinks if their health required special medicine/equipment (OR = 0.50 [0.32, 0.80]). Yet treatment effects were nonsignificant among youth without socioemotional vulnerabilities. Among mothers of children with learning problems, MTO voucher treatment (vs. controls) reduced past-month drinking (OR = 0.69 [0.47, 0.99]), but was harmful otherwise (OR = 1.22 [0.99, 1.45]). CONCLUSIONS: For low-income adolescents with special needs/socioemotional problems, housing vouchers protect against alcohol use.

Clinical Post-SARS-CoV-2 Infection Scenarios in Vaccinated and Non-Vaccinated Cancer Patients in Three German Cancer Centers: A Retrospective Analysis.

COVID-19 vaccines have become an integral element in the protection of cancer patients against SARS-CoV-2. To date, there are no direct comparisons of the course of COVID-19 infection in cancer patients between the pre- and post-vaccine era. We analyzed SARS-CoV-2 infections and their impact on cancer in COVID-19 vaccinated and non-vaccinated patients from three German cancer centers. Overall, 133 patients with SARS-CoV-2 were enrolled in pre- and post-vaccine eras: 84 non-vaccinated and 49 vaccinated, respectively. A mild course of COVID-19 was documented more frequently in vaccinated patients (49% vs. 29%), while the frequency of severe and critical courses occurred in approximately one-half of the non-vaccinated patients (22% vs. 42%, p = 0.023). Particularly, patients with hematologic neoplasms benefited from vaccination in this context (p = 0.031). Admissions to intermediate- and intensive-care units and the necessity of non-invasive and invasive respiratory support were reduced by 71% and 50% among vaccinated patients, respectively. The median length of admission was 11 days for non-vaccinated and 5 days for vaccinated patients (p = 0.002). COVID-19 mortality was reduced by 83% in vaccinated patients (p = 0.046). Finally, the median time from SARS-CoV-2 infection to restarting cancer therapy was 12 and 26 days among vaccinated and non-vaccinated groups, respectively (p = 0.002). Although this study does not have enough power to perform multivariate analyses to account for confounders, it provides data on COVID-19 in non-vaccinated and vaccinated cancer patients and illustrates the potential benefits of COVID-19 vaccines for these patients.

[Healthcare-associated infections and antimicrobial use in long-term care facilities. German results of the third European point prevalence survey HALT-3]. / Nosokomiale Infektionen und Antibiotikaanwendung in Langzeitpflegeeinrichtungen. Deutsche Ergebnisse der dritten europäischen Punkt-Prävalenz-Erhebung HALT-3.

BACKGROUND AND OBJECTIVE: The essential role of infection prevention in long-term care facilities has become evident during the current SARS-CoV­2 pandemic. In order to obtain a reliable database on nosocomial infections and antibiotic use, the European Centre for Disease Prevention and Control (ECDC) initiated the third point prevalence survey in European long-term care facilities from 2016 to 2017 (HALT-3). MATERIAL AND METHODS: In Germany, 131 facilities with 10,565 residents participated voluntarily. On a single day in 2016, the number of nosocomial infections and/or uses of antibiotics as well as care characteristics and risk factors of the residents were recorded. Infections were documented based on symptoms using an algorithm in accordance with the McGeer surveillance criteria for long-term care facilities. RESULTS: A nosocomial infection was documented in 177 residents, which corresponds to a prevalence of 1.7% (95% CI: 1.3-2.1), still low in comparison with the European prevalence (mean value 3.9%). Urinary tract infections were the most common infections at almost 50%, followed by respiratory, skin, and soft-tissue infections. The type of infection was consistent with the most common indications for antibiotic use. Antibiotic use was documented in 143 residents (prevalence of 1.4%, 95% CI: 1.1-1.7). The frequent use of fluoroquinolones with over 20% of all prescriptions was noticeable. CONCLUSIONS: The establishment of facility-based surveillance of the most common infections and antibiotic consumption, together with the creation of guidelines specifically tailored to the geriatric population, could contribute to improving infection prevention and control as well as a more rational use of antibiotics, thus increasing the quality and safety of care.

Blocking Metabotropic Glutamate Receptor Subtype 7 via the Venus Flytrap Domain Promotes a Chronic Stress-Resilient Phenotype in Mice.

Chronic psychosocial stress participates prominently in the etiology of various psychiatric conditions and comorbid somatic pathologies; however, suitable pharmacotherapy of these disorders is still of high medical need. During the last few decades, research on mGlu receptors advanced remarkably and much attention was given to the mGlu7 subtype. Here, genetic mGlu7 ablation, short-term pharmacological mGlu7 blockade, as well as siRNA-mediated knockdown of mGlu7 were shown to result in an acute anti-stress, antidepressant- and anxiolytic-like phenotype in mice. Moreover, we recently revealed a prominent stress-protective effect of genetic mGlu7 ablation also with respect to chronic psychosocial stress. In addition, we are able to demonstrate in the present study that the chronic pharmacological blockade of mGlu7 interferes with various chronic stress-induced alterations. For this, we used the chronic subordinate colony housing (CSC), a mouse model of chronic male subordination, in combination with chronic treatment with the mGlu7-selective orthosteric-like antagonist XAP044 (7-hydroxy-3-(4-iodophenoxy)-4H-chromen-4-one). Interestingly, XAP044 dose-dependently ameliorates hypothalamic-pituitary-adrenal axis dysfunctions, thymus atrophy, as well as the CSC-induced increase in innate anxiety. Taken together, our findings provide further evidence for the role of mGlu7 in chronic psychosocial stress-induced alterations and suggests the pharmacological blockade of mGlu7 as a promising therapeutic approach for the treatment of chronic stress-related pathologies in men.

"My motivation was to save": a qualitative study exploring factors influencing motivation of community healthcare workers in a cervical cancer screening program in Dschang, Cameroon.

BACKGROUND: Cervical cancer is a major public health issue among women in Cameroon and uptake of screening programs remains a challenge in many low- and middle-income countries. Community healthcare workers can play an important role in promoting cervical cancer services. This study aimed to explore factors affecting the motivation of community healthcare workers in a cervical cancer screening program in Dschang, Cameroon. METHODS: A qualitative approach including 11 in-depth individual interviews with community healthcare workers was used. The interviews were audio-recorded, transcribed and coded using thematic analysis assisted by ATLAS.ti software. RESULTS: Four women and seven men aged between 21 and 77 years old were interviewed. Community healthcare workers had high motivation. Factors affecting motivation were divided into individual and environmental level, based on a theoretical framework. Factors with a positive influence on motivation were mainly on the individual side while impeding factors were mainly associated with the environmental level. CONCLUSIONS: Key interventions to improve motivation among community healthcare workers include: (i) more training and supportive supervision; (ii) evaluation of remuneration systems by workload; and (iii) provision of job-enabling resources such as uniforms, cellphone cards and transport. TRIAL REGISTRATION: Geneva Cantonal Ethics Committee on Human Research (No. 2017-01110) and the Cameroonian National Ethics Committee for Human Health Research (No. 2018/07/1083/CE/CNERSH/SP).

Cervical cancer is the second leading cause of cancer-related death among women in Cameroon. This is mainly due to the absence of routine cervical cancer screening programs and the lack of treatment. However, even in case of availability of cervical cancer screening programs, barriers exist. Therefore, community healthcare workers have been involved successfully to increase the screening coverage. As retention of these actors remains a challenge, the main objective of this study was to identify key factors affecting their motivation aiming to suggest interventions to address motivational factors. 11 qualitative interviews with individual community healthcare workers were conducted at a cervical cancer screening program in Dschang, Cameroon. Motivation was generally high and affecting factors were divided into the individual and the environmental level. Factors with a positive influence on motivation were mainly on the individual side while impeding factors were mainly associated with the environmental level. Ongoing collaboration with community healthcare workers is beneficial for cervical cancer screening programs, and key interventions should therefore include: (i) more training and supportive supervision; (ii) evaluation of remuneration systems by workload; and (iii) provision of job-enabling resources such as uniforms, cellphone cards and transport.

Outcomes of second allogeneic stem cell transplantation and anti-relapse strategies in patients with relapsed/refractory acute myeloid leukemia: A unicentric retrospective analysis.

Second allogeneic stem cell transplantation (allo-SCT2) represents a rescue option for selected patients (pts) with relapsed/refractory (r/r) acute myeloid leukemia (AML). Still, relapse rates post-allo-SCT2 remain high and effective anti-relapse strategies and predictive biomarkers remain to be defined. We here analyzed a cohort of 41 AML patients (pts) undergoing allo-SCT2 in our center. Allo-SCT2 induced a third hematologic complete remission (CR) in 37 pts, at costs of a 36% non-relapse mortality rate. Furthermore, 19 pts eventually relapsed post allo-SCT2. Addressing relapse after allo-SCT2, 14 pts (74%) underwent cell-based anti-relapse strategies, including third allogeneic transplantation (allo-SCT3; 3/14), donor lymphocyte infusions (DLIs) combined with either 5-azacytidin and venetoclax (4/14) or chemotherapeutic agents (7/14). Notably, six of seven pts (86%) who received either allo-SCT3 or a combination therapy of DLIs, 5-azacytidine and venetoclax achieved CR despite poor cytogenetics post-allo-SCT2 (e.g., TP53). Finally, 11 of 41 pts were alive at the last follow-up (seven CR2, three CR3, one partial remission) resulting in estimated 2- and 5-year overall survival of 35% and 25%, respectively.

Determining the Minimally Effective Dose of a Clinical Candidate Adeno-Associated Virus Vector in a Mouse Model of Hemophilia A.

Hemophilia A, a bleeding disorder, affects 1:5,000 males and is caused by a deficiency of human blood coagulation factor VIII (hFVIII). Studies in mice and macaques identified AAVhu37.E03.TTR.hFVIIIco-SQ.PA75 as a clinical candidate gene therapy vector to treat hemophilia A. In this study, we sought to determine the minimally effective dose (MED) of this vector in a hemophilia A mouse model. Mice received one of four vector doses (3 × 1011-1 × 1013 genome copies [GCs]/kg) via intravenous tail vein injection; one cohort received vehicle as a control. Animals were monitored daily after vector/vehicle administration. Blood samples were collected to evaluate hFVIII activity levels and anti-hFVIII antibodies. Animals were sacrificed and necropsied on days 28 and 56; tissues were harvested for histopathological examination and blood was collected for serum chemistry panel analysis. We found no significant differences in liver transaminase levels in mice administered any vector dose compared to those administered vehicle (except for one group administered 3 × 1011 GC/kg). Total bilirubin levels were significantly elevated compared to the vehicle group following two vector doses at day 56 (1 × 1012 and 1 × 1013 GC/kg). We observed no vector-related gross or histological findings. Most microscopic findings were in the vehicle group and considered secondary to blood loss, an expected phenotype of this mouse model. Since we observed no dose-limiting safety markers, we determined that the maximally tolerated dose was greater than or equal to the highest dose tested (1 × 1013 GC/kg). Since we detected hFVIII activity in all cohorts administered vector, we conclude that the MED is 3 × 1011 GC/kg-the lowest dose evaluated in this study.

Feasibility and efficacy of salvage allogeneic stem cell transplantation in AML patients relapsing after autologous stem cell transplantation.

Autologous hematopoietic cell transplantation (HCT) is suitable for consolidation of favorable-/intermediate-risk AML patients in CR1. However, ~50% of AML patients relapse after autologous HCT, and efficacy of subsequent salvage strategies including allogeneic HCT remains unclear. We studied 123 consecutive patients with newly diagnosed AML undergoing high-dose chemotherapy (HDCT)/autologous HCT in CR1. In relapsing patients afterwards, we analyzed salvage treatments and outcomes focusing particularly on salvage allogeneic HCT. Of 123 patients, 64 (52%) relapsed after autologous HCT. Subsequently, 13 (21%) received palliative therapy, whereas 51 (79%) proceeded to salvage therapy with a curative intent. Of the 47 patients with a curative intent and who did not proceed directly to allogeneic HCT, 23 (49%) achieved CR2 or had ongoing hematologic CR1 despite molecular relapse. Finally, 30 patients (47%) received allogeneic HCT with estimated 3-year leukemia-free and overall survival rates of 33% and 43%. Hematologic remission at allogeneic HCT and lack of acute GvHD had a positive impact on OS and LFS (p < 0.05). Our study suggests that almost 80% of AML patients can undergo salvage therapy following relapse after front-line HDCT/autologous HCT. Allogeneic HCT can provide cure in one third of patients relapsing after front-line HDCT/autologous HCT.

Deep impact? Is mercury in dab (Limanda limanda) a marker for dumped munition? Results from munition dump site Kolberger Heide (Baltic Sea).

Dumped munitions contain various harmful substances which can affect marine biota like fish. One of them is mercury (Hg), included in the common explosive primer Hg fulminate. There is still a lack of knowledge whether dumped munitions impact the Hg concentrations in the Baltic Sea environment. This study aims to answer the question if dab caught at the dump site Kolberger Heide show higher Hg concentrations released from munition sources and whether Hg in fish is a usable marker for munition exposure. Therefore, a total of 251 individual dab (Limanda limanda) were analysed including 99 fish from the dump site. In fish from the Kolberger Heide, no elevated Hg concentrations were found compared to reference sites when age-dependent bioaccumulation of mercury was considered. Therefore we conclude that Hg in fish is no suitable indicator for exposure to munition dumping, e.g. in the frame of possible future monitoring studies as Hg exposure originating from dumped munition is only a small contributor to overall Hg exposure of fish.

"Cervical cancer screening: awareness is not enough". Understanding barriers to screening among women in West Cameroon-a qualitative study using focus groups.

BACKGROUND: Cervical cancer is the second leading cause of cancer-related death among women in sub-Saharan countries, constituting a major public health concern. In Cameroon, cervical cancer ranks as the second most common type of cancer among women and the leading cause of cancer-related deaths, mainly due to the lack of prevention. OBJECTIVES: Our first and main objective was to understand the barriers affecting women's decision-making process regarding participation in a cervical cancer screening program in the Dschang district (West Cameroon). Second, we aimed to explore the acceptability and perception of a single-visit approach (screen and treat). METHODS: A qualitative study using focus groups (FGs) was conducted from February to March 2020. Female participants aged between 30 and 49 years and their male partners were invited to participate. Thematic analysis was used, and barriers were classified according to the three-delay model of Thaddeus and Maine. RESULTS: In total, six FGs with 43 participants (31 women and 12 men) were conducted. The most important barriers were lack of health literacy, low accessibility of the program (in respect to cost and distance), and disrespectful treatment by healthcare workers. CONCLUSIONS: Our study identified three needs: (1) enhancing health literacy; (2) improving the delivery of cervical cancer screening in rural areas; and (3) providing training for healthcare providers and community healthcare workers to improve patient-provider-communication. Trial registration Ethical Cantonal Board of Geneva, Switzerland (CCER, N°2017-0110 and CER-amendment n°3) and Cameroonian National Ethics Committee for Human Health Research (N°2018/07/1083/CE/CNERSH/SP). NCT: 03757299.

Cervical cancer is the second leading cause of cancer-related death among women in sub-Saharan countries, constituting a major public health concern. In Cameroon, cervical cancer ranks as the second most common type of cancer among women and is the leading cause of cancer-related deaths, mainly due to the lack of prevention measures, such as cervical cancer screening.The main aim of the current study was to understand barriers that affect women's decision-making processes regarding participation in a cervical cancer screening program in the Dschang district in West Cameroon.A qualitative study methodology using focus group discussions was conducted from February to March 2020. Female participants aged between 30 and 49 years and their male partners were invited to participate.In total, six discussion groups with 43 participants (31 women and 12 men) were conducted. The most important barriers were a lack of health literacy, limited access to the program because of cost and distance, and disrespectful treatment by healthcare workers.Our results identified three key areas for improvement: first, increasing health literacy; second, providing cervical cancer screening in rural areas; and third, training healthcare providers and community healthcare workers in better patient-provider-communication.

Psychological Stress among Students in Health-Related Fields during the COVID-19 Pandemic: Results of a Cross-Sectional Study at Selected Munich Universities.

The COVID-19 pandemic has been a challenging period of upheaval for higher education students. This study aims to assess the factors associated with psychological stress during the COVID-19 pandemic among a sample of students in health-related fields at Munich universities in Germany. Students (n = 623) from KSH Munich and LMU Munich completed an online cross-sectional survey. Information on demographics and academic and everyday difficulties due to the COVID-19 pandemic as well as data on physical and mental health were collected. Multivariable logistic regression analyses were performed to identify factors associated with the outcome. The prevalence for higher psychological stress was 44% among the study population. Factors associated with higher psychological stress were: lower overall life satisfaction (p < 0.0001), worsened health situation (p < 0.0001), lack of social support (p = 0.0301) and social interaction (p = 0.0115), worries about financial difficulties due to loss of income (p = 0.0134), stressful thoughts about a second wave (p < 0.0001), feeling unable to positively influence the situation (p = 0.0262) and study-related effects, such as perceived study burden (p = 0.0003) and likely delay in studies (p = 0.0178)). The COVID-19 pandemic is having a significant negative impact on the mental health of students in health-related fields. Proactive efforts to support the mental health and well-being of students are needed.

Diagnostic, Clinical and Post-SARS-CoV-2 Scenarios in Cancer Patients with SARS-CoV-2: Retrospective Analysis in Three German Cancer Centers.

Oncologists face challenges in the management of SARS-CoV-2 infections and post-SARS-CoV-2 cancer treatment. We analyzed diagnostic, clinical and post-SARS-CoV-2 scenarios in patients from three German cancer centers with RT-PCR confirmed SARS-CoV-2 infection. Sixty-three patients with SARS-CoV-2 and hematologic or solid neoplasms were included. Thirty patients were initially asymptomatic, 10 of whom developed COVID-19 symptoms subsequently. Altogether 20 (32%) patients were asymptomatic, 18 (29%) had mild, 12 (19%) severe and 13 (20%) critical courses. Lymphocytopenia increased risk of severe/critical COVID-19 three-fold (p = 0.015). Asymptomatic course was not associated with age, remission status, therapies or co-morbidities. Secondary bacterial infection accompanied more than one third of critical COVID-19 cases. Treatment was delayed post-SARS-CoV-2 in 46 patients, 9 of whom developed progressive disease (PD). Cancer therapy was modified in 8 SARS-CoV-2 survivors because of deteriorating performance or PD. At the last follow-up, 17 patients had died from COVID-19 (n = 8) or PD (n = 9) giving an estimated 73% four-month overall survival rate. SARS-CoV-2 infection has a heterogenous course in cancer patients. Lymphocytopenia carries a significant risk of severe/critical COVID-19. SARS-CoV-2 disruption of therapy is as serious as SARS-CoV-2 infection itself. Careful surveillance will allow early restart of the anti-cancer treatment.