Search

Background: Sinonasal adenocarcinoma is a rare cancer, encompassing two different entities, the intestinal-type sinonasal adenocarcinoma (ITAC) and the non-intestinal-type sinonasal adenocarcinoma (non-ITAC). Occurrence of ITAC is strongly associated with exposure to hardwood dusts. In countries with predominant exposure to softwood dust the occurrence of sinonasal adenocarcinomas is lower and the relative amount of non-ITACs to ITACs is higher. The molecular mechanisms behind the tumorigenic effects of wood dust remain largely unknown., Methods: We carried out whole-genome sequencing of formalin-fixed paraffin-embedded (FFPE) samples of sinonasal adenocarcinomas from ten wood dust-exposed and six non-exposed individuals, with partial tobacco exposure data. Sequences were analyzed for the presence of mutational signatures matching COSMIC database signatures. Driver mutations and CN variant regions were characterized., Results: Mutation burden was higher in samples of wood dust-exposed patients (p = 0.016). Reactive oxygen species (ROS) damage-related mutational signatures were almost exclusively identified in ITAC subtype samples (p = 0.00055). Tobacco smoke mutational signatures were observed in samples of patients with tobacco exposure or missing information, but not in samples from non-exposed patients. A tetraploidy copy number (CN) signature was enriched in ITAC subtype (p = 0.042). CN variation included recurrent gains in COSMIC Cancer Gene Census genes TERT, SDHA, RAC1, ETV1, PCM1, and MYC. Pathogenic variants were observed most frequently in TP53, NF1, CHD2, BRAF, APC, and LRP1B. Driver mutations and copy number gains did not segregate by subtype., Conclusions: Our analysis identified distinct mutational characteristics in ITAC and non-ITAC. Mutational signature analysis may eventually become useful for documentation of occupation-related cancer, while the exact mechanisms behind wood dust-driven carcinogenesis remain elusive. The presence of homologous recombination deficiency signatures implies a novel opportunity for treatment, but further studies are needed., (© 2024. The Author(s).)

Objectives: The ExPAND Mifepristone (ExPAND) learning collaborative aims to support primary care providers in overcoming logistical barriers to mifepristone provision. This qualitative study describes clinician and staff perspectives on the impact of ExPAND in two federally qualified health center networks (FQHCs)., Study Design: Researchers conducted semi-structured qualitative interview with a purposive sample of clinicians, staff, and leadership from two Illinois FQHCs. We analyzed transcripts in batches using modified grounded theory to identify themes regarding the reception of ExPAND and barriers to and facilitators of mifepristone implementation., Results: Participants (n = 13) expressed strong support for providing mifepristone for miscarriage management at their clinics. Most also personally supported mifepristone for abortion care. Many participants felt that ExPAND reflected their clinics' values, as it strengthens the primary care relationship, emphasizes patient-centered care, and addresses disparities in access. Barriers to implementation included fear that providing abortion care would jeopardize FQHC funding and logistical hurdles due to the coronavirus disease pandemic., Conclusions: Participants felt that mifepristone provision in primary care was an important service, and that ExPAND helped achieve that goal. Future clinics participating in ExPAND would benefit from education about how FQHCs can provide mifepristone for abortion care while complying with federal funding restrictions., Implications: Learning collaboratives like ExPAND can prepare primary care clinics to provide mifepristone. Participants describe a clear benefit of mifepristone integration to their patients, and they report mifepristone integration aligns with clinic values., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: Knowledge on mental health consultations in immigration detention and characteristics of people receiving consultations is scarce. Based on a sample of 230 adult men in immigration detention in Switzerland, we aimed to: (1) Quantify the proportion of persons receiving mental health consultations during detention; and (2) Identify socio-demographic and clinical characteristics associated with mental health consultations. Methods: Retrospective observational study with a cross-sectional design. Prevalence estimates, logistic regressions, and contingency tables were used to analyse the data. Results: A total of 30% of the sample received mental health consultations during detention. Time spent in immigration detention, mental health problems during detention, use of psychotropic medication, and self-harm were associated with mental health consultations. Although mental health consultations are provided to people with more severe mental health problems, 41% of persons with assessed mental health needs during the initial screening and 26% of those who self-harmed during detention did not receive mental health consultations. Conclusion: Mental health resources and screening procedures could be improved to ensure that mental health consultations are matched to clinical need in immigration detention settings., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2024 Gonçalves, Heller, Bachmann, Barbolini, Fuhrer, Gétaz, Luke, Wolff and Baggio.)

Background: Attention-deficit hyperactivity disorder (ADHD) is characterized by difficulty paying attention, poor impulse control, and hyperactive behavior. It is associated with several adverse health and social outcomes and leads to an increased risk of criminality and recidivism. Worldwide, ADHD is thus highly prevalent in prisons. However, ADHD treatment has been neglected in such environments. Stimulant medications such as osmotic-release oral system methylphenidate (OROS-MPH) are first-line treatments in the general population, but they are under-prescribed in prisons due to concerns about abuse, even though such claims are not empirically supported. This project aims to compare the efficacy of a 3-month in-prison OROS-MPH vs. placebo treatment on the severity of core ADHD symptoms and relevant in- and post-prison outcomes., Methods: This study is a phase III, double-blinded, randomized, superiority, controlled trial of OROS-MPH vs. placebo. After randomization, the participants will receive 3 months of treatment with OROS-MPH or placebo (1:1 ratio) while incarcerated. Upon release, all participants will be offered the treatment (OROS-MPH) for 1 year but will remain blinded to their initial study group. The study will be conducted at the Division of Prison Health, Geneva, Switzerland, among incarcerated men (n = 150). Measures will include (1) investigator-rated ADHD symptoms, (2) acute events collected by the medical and prison teams, (3) assessment of the risk of recidivism, (4) medication side effects, (5) medication adherence, (6) study retention, (7) health care/prison costs, and (8) 1-year recidivism. Analyses will include bivariable and multivariable modeling (e.g., regression models, mixed-effects models, survival analyses) and an economic evaluation (cost-benefit analysis)., Discussion: We expect that early identification and treatment of ADHD in prison will be an important public health opportunity and a cost-effective approach that is likely to reduce the vulnerability of incarcerated individuals and promote pathways out of criminal involvement. The study will also promote standards of care for people with ADHD in prison and provide recommendations for continuity of care after release., Trial Registration: ClinicalTrials.gov NCT05842330 . Registered on June 5, 2023. Kofam.ch SNCTP000005388. Registered on July 17, 2023., (© 2024. The Author(s).)

Objectives: Nearly one-third of low-income women of reproductive age in the U.S. receive care in federally qualified community health centers, but comprehensive reproductive care is not consistently provided. Illinois Contraceptive Access Now (ICAN!) is an initiative addressing the access gap to high-quality contraceptive care with a focus on normalizing reproductive health screening for patients in federally qualified community health centers (FQHCs)., Study Design: This multi-method program evaluation used the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework, with retrospective and prospective data collection from three Illinois FQHCs who participated as Quality Hubs, and from a Community Advisory Board. We conducted descriptive analysis of patient surveys using the Person-Centered Contraceptive Counseling (PCCC) measure (n = 142); clinician and staff pre-and post-training surveys (n = 210); and Community Advisory Board surveys (n = 8) collecting quantitative and qualitative feedback. We ran logistic regression on claims data from 15- to 49-year-old patients identified as female at birth (n = 103,756)., Results: Reach assessment showed patients receiving contraceptive or preconception care increased from 1063 per month in 2020 to 1236 per month in 2021 (16% increase), while general volume increased 2%. Effectiveness showed most patients (78%) described the quality of contraceptive counseling as "excellent" on the PCCC. Adoption assessment showed knowledge increases after clinical training on Modern Contraception (85% pre-training, 95% post-training) and Reproductive Justice (RJ) (58% pre-training, 70% post-training). Implementation assessment found that most Community Advisory Board members felt ICAN! was responsive to community needs., Conclusions: The ICAN! demonstration year increased provider knowledge and volume of reproductive care at three Illinois FQHCs., Implications: Contraceptive access initiatives that operationalize same day access to birth control methods while training FQHC providers on RJ and modern contraception, show promise on several measures. Early evidence from ICAN! indicates increased reproductive health service provision, as well as increases in provider knowledge of RJ and modern contraceptive care., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: It remains unclear whether radiation therapy (RT) has an impact on the development of secondary primary cancer (SC) in rectal cancer (RC) patients, especially within the true pelvis., Aim: To examine the incidence of SC in a population-based cohort of RC after surgical treatment with or without radiation therapy (RT, NRT)., Patients and Methods: The epidemiological cohort consisting of 13,919 RC patients with primary M0 stage diagnosed between 1998 and 2019 was collected from cancer registry data of Upper Bavaria. Competing risk analyses were conducted regarding the development of SC on 11 687 first malignancies, stratified by RT/NRT. A propensity score (PS) was generated by logistic regression modeling of RT to repeat competing risk analyses on a PS-matched cohort., Results: The median age (interquartile range) of the epidemiological cohort was 68.9 years (60.4-76.7). About 60.8%, were men, 38.7% had UICC III, 35.8% of tumors were localized lower than 8 cm, 41.3% underwent RT. Only 17.1% of patients older than 80 years at diagnosis received RT. In general, RT patients were 5 years younger than NRT patients (65.9 years [58.0-73.0] vs. 71.3 years [62.4-79.2], P < .0001). The 20-year cumulative incidence of SC was 16.5% in RT and 17.4% in NRT patients (P = .2298). Men with RT had a lower risk of prostate cancer (HR = 0.55, 95%CI [0.34-0.91], P = .0168). In the PS-matched cohort, RT patients had a significantly higher risk of bladder cancer during follow-up (10-year cumulative incidence of 1.1% vs. 0.6% in NRT). The direction of the RT effects in men and women and different tumor sites may cancel each other., Conclusion: A protective effect of RT in rectal cancer patients on developing prostate SC by half is reproduced. Further analyses studying the long-term SC risks of RT should essentially focus on stratification by sex, and focus on more recent data., Competing Interests: Disclosure All authors declare no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Human cerebral organoids (HCOs) are model systems that enable researchers to investigate the human brain in ways that had previously been impossible. The emergence of HCOs was accompanied by both expert and layperson discussions concerning the possibility of these novel entities developing sentience or consciousness. Such concerns are reflected in deliberations about how to handle and regulate their use. This perspective article resulted from an international and interdisciplinary research retreat "Ethical, Legal and Social Aspects of Human Cerebral Organoids and their Governance in Germany, the United Kingdom and the United States", which took place in Tübingen, Germany, in August 2022. The retreat focused on whether HCO research requires new ethical and regulatory approaches. It addressed epistemic issues around the detection and theorisation of consciousness, ethical concerns around moral status and research conduct, difficulties for legislation and guidelines managing these entities, and public engagement., Competing Interests: JS is a member of Merck KGaA’s Ethics Advisory Panel and Stem Cell Research Oversight Committee; a member of IQVIA’s Ethics Advisory Panel; a member of Aspen Neurosciences Clinical Advisory Panel; and previously a member of a Merck Data Monitoring Committee and a consultant to Biogen. The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pichl, Ranisch, Altinok, Antonakaki, Barnhart, Bassil, Boyd, Chinaia, Diner, Gaillard, Greely, Jowitt, Kreitmair, Lawrence, Lee, McKeown, Sachdev, Schicktanz, Sugarman, Trettenbach, Wiese, Wolff and Árnason.)

Background: Rectal cancer treatment has improved considerably due to the introduction of total meso-rectal excision, radio-chemotherapy, and high-resolution imaging. The aim of this observational cohort study was to quantify the effectiveness of these advances using high-quality data from a representative cohort of patients., Methods: 20 281 non-metastasized cases retrieved from the Munich Cancer Registry database were divided into three time periods corresponding to before (1988-1997), partial (1998-2007), and full implementation (2008-2019) of clinical advances. Early-onset (<50 yrs.), middle-aged, elderly patient subgroups (> 70 yrs.) were compared. The overall effectiveness of evidence-based guideline adherence was also examined., Results: Median survival improved by 1.5 yrs. from the first to the last time period. Relative survival increased from 74.9% (5-yr 95%CI[73.3 - 76.6]) to 79.2% (95%CI[77.8 - 80.5]). The incidence of locoregional recurrences was reduced dramatically by more than half (5-yr 17.7% (95%CI[16.5 - 18.8]); 6.7% (95%CI[6.1 - 7.3])). Gains in 5-yr relative survival were limited to early-onset and middle-aged patients with no significant improvement seen in elderly patients (Female 68.6% [63.9 - 73.3] to 67.6% [64.0 - 71.2]; Male 71.7% [65.9 - 77.4] to 74.0% [70.8 - 77.2])., Conclusions: Real-world evidence suggests that recent treatment advances have lead to an increase in prognosis for rectal cancer patients. However, more effort should be made to improve the implementation of new developments in elderly patients. Especially considering, that these cases represent a growing majority of diagnosed patients., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: III-V semiconductor nanowires are envisioned as being integrated in optoelectronic devices in the near future. However, the perspective of mass production of these nanowires raises concern for human safety due to their asbestos- and carbon nanotube-like properties, including their high aspect ratio shape. Indeed, III-V nanowires have similar dimensions as Mitsui-7 multi-walled carbon nanotubes, which induce lung cancer by inhalation in rats. It is therefore urgent to investigate the toxicological effects following lung exposure to III-V nanowires prior to their use in industrial production, which entails risk of human exposure. Here, female C57BL/6J mice were exposed to 2, 6, and 18 µg (0.12, 0.35 and 1.1 mg/kg bw) of gallium phosphide (III-V) nanowires (99 nm diameter, 3.7 μm length) by intratracheal instillation and the toxicity was investigated 1, 3, 28 days and 3 months after exposure. Mitsui-7 multi-walled carbon nanotubes and carbon black Printex 90 nanoparticles were used as benchmark nanomaterials., Results: Gallium phosphide nanowires induced genotoxicity in bronchoalveolar lavage cells and acute inflammation with eosinophilia observable both in bronchoalveolar lavage and lung tissue (1 and 3 days post-exposure). The inflammatory response was comparable to the response following exposure to Mitsui-7 multi-walled carbon nanotubes at similar dose levels. The nanowires underwent partial dissolution in the lung resulting in thinner nanowires, with an estimated in vivo half-life of 3 months. Despite the partial dissolution, nanowires were detected in lung, liver, spleen, kidney, uterus and brain 3 months after exposure., Conclusion: Pulmonary exposure to gallium phosphide nanowires caused similar toxicological effects as the multi-walled carbon nanotube Mitsui-7., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Daily in-hand medication dispensing in prisons and jails is resource intensive, disempowering, and nonconfidential. This research aimed to assess a nurse-initiated, low-frequency medication dispensing system using personal lockable boxes., Methods: A cross-sectional study was carried out in a Swiss prison involving 47 box users and 19 custodial officers., Findings: Box users agreed or strongly agreed about the perceived advantages of the box system, including user-friendliness, lower theft risk, and increased dignity, confidentiality, compliance, and autonomy to self-manage medication. Officers, who must accompany nurses during dispensing rounds, concurred that medication boxes were more time-efficient and improved role differentiation between custodial and clinical staff. Patients and officers were overall satisfied with the system and would recommend scaling it up in other facilities., Discussion: This study suggests that medication boxes are feasible, acceptable, easy to use, and secure. Boxes could promote patients' autonomy, protect confidentiality, and allow nurses to dedicate more time to individual visits and health promotion and prevention activities., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc.)

Nanoparticles are extensively used in industrial products or as food additives. However, despite their contribution to improving our quality of life, concerns have been raised regarding their potential impact on occupational and public health. To speed up research assessing nanoparticle-related hazards, this study was undertaken to identify early markers of harmful effects on the lungs. Female Sprague Dawley rats were either exposed to crystalline silica DQ-12 with instillation, or to titanium dioxide P25, carbon black Printex-90, or multi-walled carbon nanotube Mitsui-7 with nose-only inhalation. Tissues were collected at three post-exposure time points to assess short- and long-term effects. All particles induced lung inflammation. Histopathological and biochemical analyses revealed phospholipid accumulation, lipoproteinosis, and interstitial thickening with collagen deposition after exposure to DQ-12. Exposure to the highest dose of Printex-90 and Mitsui-7, but not P25, induced some phospholipid accumulation. Comparable histopathological changes were observed following exposure to P25, Printex-90, and Mitsui-7. Comparison of overall gene expression profiles identified 15 potential early markers of adverse lung outcomes induced by spherical particles. With Mitsui-7, a distinct gene expression signature was observed, suggesting that carbon nanotubes trigger different toxicity mechanisms to spherical particles.

Carbon nanotubes (CNTs) are nanomaterials presenting an occupational inhalation risk during production or handling. The International Agency for Research on Cancer classified one CNT, Mitsui-7 (MWNT-7), as 'possibly carcinogenic to humans'. In recognition of their similarities, a proposal has been submitted to the risk assessment committee of ECHA to classify all fibers with 'Fibre Paradigm' (FP)-compatible dimensions as carcinogenic. However, there is a lack of clarity surrounding the toxicity of fibers that do not fit the FP criteria. In this study, we compared the effects of the FP-compatible Mitsui-7, to those of NM-403, a CNT that is too short and thin to fit the paradigm. Female Sprague Dawley rats deficient for p53 (GMO) and wild type (WT) rats were exposed to the two CNTs (0.25 mg/rat/week) by intratracheal instillation. Animals (GMO and WT) were exposed weekly for four consecutive weeks and were sacrificed 3 days or 8 months after the last instillation. Exposure to both CNTs induced acute lung inflammation. However, persistent inflammation at 8 months was only observed in the lungs of rats exposed to NM-403. In addition to the persistent inflammation, NM-403 stimulated hyperplasic changes in rat lungs, and no adenomas or carcinomas were detected. The degree and extent of hyperplasia was significantly more pronounced in GMO rats. These results suggest that CNT not meeting the FP criteria can cause persistent inflammation and hyperplasia. Consequently, their health effects should be carefully assessed.

Providing insights on refusal to participate in research is critical to achieve a better understanding of the non-response bias. Little is known on people who refused to participate, especially in hard-to-reach populations such as detained persons. This study investigated the potential non-response bias among detained persons, comparing participants who accepted or refused to sign a one-time general informed consent. We used data collected in a cross-sectional study primary designed to evaluate a one-time general informed consent for research. A total of 190 participants were included in the study (response rate = 84.7%). The main outcome was the acceptance to sign the informed consent, used as a proxy to evaluate non-response. We collected sociodemographic variables, health literacy, and self-reported clinical information. A total of 83.2% of the participants signed the informed consent. In the multivariable model after lasso selection and according to the relative bias, the most important predictors were the level of education (OR = 2.13, bias = 20.7%), health insurance status (OR = 2.04, bias = 7.8%), need of another study language (OR = 0.21, bias = 39.4%), health literacy (OR = 2.20, bias = 10.0%), and region of origin (not included in the lasso regression model, bias = 9.2%). Clinical characteristics were not significantly associated with the main outcome and had low relative biases (≤ 2.7%). Refusers were more likely to have social vulnerabilities than consenters, but clinical vulnerabilities were similar in both groups. The non-response bias probably occurred in this prison population. Therefore, efforts should be made to reach this vulnerable population, improve participation in research, and ensure a fair and equitable distribution of research benefits., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Baggio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Acute phase response (APR) is characterized by a change in concentration of different proteins, including C-reactive protein and serum amyloid A (SAA) that can be linked to both exposure to metal oxide nanomaterials and risk of cardiovascular diseases. In this study, we intratracheally exposed mice to ZnO, CuO, Al 2 O 3 , SnO 2 and TiO 2 and carbon black (Printex 90) nanomaterials with a wide range in phagolysosomal solubility. We subsequently assessed neutrophil numbers, protein and lactate dehydrogenase activity in bronchoalveolar lavage fluid, Saa3 and Saa1 mRNA levels in lung and liver tissue, respectively, and SAA3 and SAA1/2 in plasma. Endpoints were analyzed 1 and 28 days after exposure, including histopathology of lung and liver tissues., Results: All nanomaterials induced pulmonary inflammation after 1 day, and exposure to ZnO, CuO, SnO 2 , TiO 2 and Printex 90 increased Saa3 mRNA levels in lungs and Saa1 mRNA levels in liver. Additionally, CuO, SnO 2 , TiO 2 and Printex 90 increased plasma levels of SAA3 and SAA1/2. Acute phase response was predicted by deposited surface area for insoluble metal oxides, 1 and 28 days post-exposure., Conclusion: Soluble and insoluble metal oxides induced dose-dependent APR with different time dependency. Neutrophil influx, Saa3 mRNA levels in lung tissue and plasma SAA3 levels correlated across all studied nanomaterials, suggesting that these endpoints can be used as biomarkers of acute phase response and cardiovascular disease risk following exposure to soluble and insoluble particles., (© 2023. The Author(s).)

Introduction: Asbestos is a global occupational health hazard, and exposure to it by inhalation predisposes to interstitial as well as malignant pulmonary morbidity. Over time, asbestos fibers embedded in lung tissue can become coated with iron-rich proteins and mucopolysaccharides, after which they are called asbestos bodies (ABs) and can be detected in light microscopy (LM). Bronchoalveolar lavage, a cytological sample from the lower airways, is one of the methods for diagnosing lung asbestosis and related morbidity. Search for ABs in these samples is generally laborious and time-consuming. We describe a novel diagnostic method, which implements deep learning neural network technology for the detection of ABs in bronchoalveolar lavage samples (BALs)., Methods: BALs with suspicion of asbestos exposure were scanned as whole slide images (WSIs) and uploaded to a cloud-based virtual microscopy platform with a neural network training interface. The images were used for training and testing a neural network model capable of recognizing ABs. To prioritize the model's sensitivity, we allowed it to also make false-positive suggestions. To test the model, we compared its performance to standard LM diagnostic data as well as the ground truth (GT) number of ABs, which we established by a thorough manual search of the WSIs., Results: We were able to reach overall sensitivity of 93.4% (95% CI: 90.3-95.7%) in the detection of ABs in comparison to their GT number. Compared to standard LM diagnostic data, our model showed equal to or higher sensitivity in most cases., Conclusion: Our results indicate that deep learning neural network technology offers promising diagnostic tools for routine assessment of BALs. However, at this stage, a human expert is required to confirm the findings., (© 2023 S. Karger AG, Basel.)

Background: Artificial intelligence (AI) techniques are promising in early diagnosis of skin diseases. However, a precondition for their success is the access to large-scaled annotated data. Until now, obtaining this data has only been feasible with very high personnel and financial resources., Objectives: The aim of this study was to overcome the obstacle caused by the scarcity of labelled data., Methods: To simulate the scenario of label shortage, we discarded a proportion of labels of the training set. The training set consisted of both labelled and unlabelled images. We then leveraged a self-supervised learning technique to pretrain the AI model on the unlabelled images. Next, we fine-tuned the pretrained model on the labelled images., Results: When the images in the training dataset were fully labelled, the self-supervised pretrained model achieved 95.7% of accuracy, 91.7% of precision and 90.7% of sensitivity. When only 10% of the data were labelled, the model could still yield 87.7% of accuracy, 81.7% of precision and 68.6% of sensitivity. In addition, we also empirically verified that the AI model and dermatologists are consistent in visually inspecting the skin images., Conclusions: The experimental results demonstrate the great potential of the self-supervised learning in alleviating the scarcity of annotated data., (© 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Dialysis-induced changes in plasma sodium concentration may cause undesirable side effects. To prevent these, the sodium content in dialysis fluid has to be individualized based on the patient's plasma sodium concentration. In this paper, we describe a simple conductivity based method for measuring the plasma sodium concentration. The method is based on performing a bypass during which the residual volume on the dialysate side of the dialyzer at least partially adopts the sodium concentration on the blood side. The conductivity at dialysate outlet of the dialyzer after the end of bypass corresponds to the sodium concentration. We show that already 14 s of bypass are sufficient to subsequently measure a conductivity that correlates with the blood-side sodium concentration. Thus, the short bypass method allows a time saving of 88% compared to the long bypass of 120 s. In vitro experiments with bovine blood show that plasma sodium concentration can be non-invasively and time-efficiently measured during dialysis. Bland Altman analysis reveals a bias of 0.28 mmol/l and limits of agreement of -3.17 and 3.74 mmol/l for the long bypass. For the short bypass, bias is 0.09 mmol/l and limits are -3.90 and 4.08 mmol/l. Since the method presented is based on established conductivity cells, no additional sensors are required, so that the method could be easily implemented in dialysis machines. In future, performing a bypass at the beginning of a treatment may be used to adjust the composition of dialysis fluid individually for each patient.

Purpose: Prisons can be epicentres of infectious diseases. However, empirical evidence on the impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in prison is still scarce. This study aims to estimate the seroprevalence rates of anti-SARS-CoV-2 in the largest and most crowded Swiss prison and compare them with the seroprevalence rate in the general population., Design/methodology/approach: A cross-sectional study was conducted in June 2020, one month after the first wave of SARS-CoV-2 in Switzerland. Groups included: people living in detention (PLDs) detained before the beginning of the pandemic ( n = 116), PLDs incarcerated after the beginning of the pandemic ( n = 61), prison staff and prison healthcare workers ( n = 227) and a sample from the general population in the same time period ( n = 3,404). The authors assessed anti-SARS-CoV-2 IgG antibodies., Findings: PLDs who were incarcerated before the beginning of the pandemic had a significantly lower seroprevalence rate [0.9%, confidence interval (CI)95%: 0.1%-5.9%] compared to the general population (6.3%, CI 95%: 5.6-7.3%) ( p = 0.041). The differences between PLDs who were incarcerated before and other groups were marginally significant (PLDs incarcerated after the beginning of the pandemic: 6.6%, CI 95%: 2.5%-16.6%, p = 0.063; prison staff CI 95%: 4.8%, 2.7%-8.6%, p = 0.093). The seroprevalence of prison staff was only slightly and non-significantly lower than that of the general population., Originality/value: During the first wave, despite overcrowding and interaction with the community, the prison was not a hotspot of SARS-CoV-2 infection. Preventive measures probably helped avoiding clusters of infection. The authors suggest that preventive measures that impact social welfare could be relaxed when overall circulation in the community is low to prevent the negative impact of isolation., (© Emerald Publishing Limited.)

Importance: Few studies are available on informed consent (IC) among detained persons, even with ethics being a critical aspect of prison research. In IC research, audiovisual material seems to improve understanding and satisfaction compared with conventional paper-based material, but findings remain unclear., Objective: To compare audiovisual and paper-based materials for 1-time general IC for research in prisons., Design, Setting, and Participants: This cross-sectional randomized clinical trial was conducted in 2 corrections facilities in Switzerland (an adult prison and a juvenile detention center). The study was conducted from December 14, 2019, to December 2, 2020, in the adult prison and from January 15, 2020, to September 9, 2021, in the juvenile detention center. In the adult prison, study participation was offered to detained persons visiting the medical unit (response rate, 84.7%). In the juvenile detention center, all newly incarcerated adolescents were invited to participate (response rate, 98.0%)., Interventions: Participants were randomized to receive paper-based conventional material or to watch a 4-minute video. Materials included the same legal information, as required by the Swiss Federal Act on Research Involving Human Beings., Main Outcomes and Measures: The main outcome was acceptance to sign the IC form. Secondary outcomes included understanding, evaluation, and time to read or watch the IC material., Results: The study included 190 adults (mean [SD] age, 35.0 [11.8] years; 190 [100%] male) and 100 adolescents (mean [SD] age, 16.0 [1.1] years; 83 [83.0%] male). In the adult prison, no significant differences were found between groups in acceptance to sign the IC form (77 [81.1%] for paper-based material and 81 [85.3%] for audiovisual material; P = .39) and to evaluate it (mean [SD] correct responses, 5.09 [1.13] for paper-based material and 5.01 [1.07] for audiovisual material; P = .81). Understanding was significantly higher in the audiovisual material group (mean [SD] correct responses, 5.09 [1.84]) compared with the paper-based material group (mean [SD] correct responses, 4.61 [1.70]; P = .04). In the juvenile detention center, individuals in the audiovisual material group were more likely to sign the IC form (44 [89.8%]) than the paper-based material group (35 [68.6%], P = .006). No significant difference was found between groups for understanding and evaluation. Adults took a mean (SD) of 5 (2) minutes to read the paper material, and adolescents took 7 (3) minutes., Conclusions and Relevance: Given the small benefit of audiovisual material, these findings suggest that giving detained adults and prison health care staff a choice regarding IC material is best. For adolescents, audiovisual material should be provided. Future studies should focus on increasing understanding of the IC process., Trial Registration: ClinicalTrials.gov Identifier: NCT05505058.

Introduction: Malignant pleural mesothelioma (MPM) is associated with poor prognosis and is strongly associated with occupational asbestos exposure. Given the importance of asbestos exposure in MPM pathogenesis, we retrospectively analyzed the types and concentrations of asbestos fibers within the lung tissues of patients with MPM and investigated their effects on all-cause mortality., Methods: We formed a national data set of patients with MPM identified from the Finnish Cancer Registry and Statistics Finland. These data were merged with pulmonary asbestos fiber analysis results received from the Finnish Institute of Occupational Health., Results: We identified 590 patients with MPM who underwent pulmonary asbestos fiber analysis. The median asbestos concentration within dry lung tissue was 3.20 million fibers/gram (range: 0 - 1700 million fibers/gram). Crocidolite and anthophyllite were the most prevalent asbestos fiber types detected in lung tissue. The multivariable risk of death analyses, where changes over time were accounted for, revealed that total asbestos fiber concentration was associated with increased mortality. Nevertheless, no difference in mortality was noted between different fiber types., Conclusions: Our study revealed that pulmonary fiber concentrations correlated with the manner of asbestos usage. Anthophyllite was identified as the sole fiber in a sizable proportion of cases, supporting its independent role in the pathogenesis of MPM. Our findings suggest that asbestos fiber burden, but not fiber type, may have an impact on the prognosis of MPM., (Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Cellulose nanofibrils (CNFs) have emerged as sustainable options for a wide range of applications. However, the high aspect ratio and biopersistence of CNFs raise concerns about potential health effects. Here, we evaluated the in vivo pulmonary and systemic toxicity of unmodified (U-CNF), carboxymethylated (C-CNF), and TEMPO (2,2,6,6-tetramethyl-piperidin-1-oxyl)-oxidized (T-CNF) CNFs, fibrillated in the same way and administered to mice by repeated (3×) pharyngeal aspiration (14, 28, and 56 μg/mouse/aspiration). Toxic effects were assessed up to 90 days after the last administration. Some mice were treated with T-CNF samples spiked with lipopolysaccharide (LPS; 0.02-50 ng/mouse/aspiration) to assess the role of endotoxin contamination. The CNFs induced an acute inflammatory reaction that subsided within 90 days, except for T-CNF. At 90 days post-administration, an increased DNA damage was observed in bronchoalveolar lavage and hepatic cells after exposure to T-CNF and C-CNF, respectively. Besides, LPS contamination dose-dependently increased the hepatic genotoxic effects of T-CNF.

Administrative detention or deprivation of liberty of migrants is a response to a decision by the authorities to remove those who have refused to leave voluntarily. These people are incarcerated not for having committed a crime, but for staying illegally in Switzerland. They often find themselves in a precarious situation, suffering from psychological or somatic illnesses that may be linked to their migration path. In most cases, they do not wish to return to their country and have many psychological or physical defences to oppose the decision of the authorities organising the removal. The health care provider is therefore faced with many challenges in order to carry out the many tasks of prison medicine while respecting fundamental ethical principles., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

People living in detention are at high risk of suicidal behaviour, with an incidence of suicides 3- to 9-fold higher compared to the general population. During the SARS-CoV-2 pandemic, suicidality among some disadvantaged populations increased and this trend was also observed in Swiss prisons. This article describes the clinical, psychosocial, institutional, criminological, and judicial factors associated with an increased risk of suicide attempt, as well as those that may lead to increased depression and other psychiatric disorders in the context of the pandemic in detention. Solutions are proposed to limit the incidence and consequences of these events in this vulnerable population., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Prisons concentrate people with multiple vulnerabilities who are exposed to violations of human rights, without any exception, including Switzerland. Independent monitoring bodies play an important role in preventing ill-treatment in detention. The most effective monitoring body worldwide is the European Committee for the Prevention of Torture (CPT), which bases its work on a European Convention that guarantees unrestricted access to detention facilities and all documents, including medical documents, in the member states of the Council of Europe. This article summarizes the main recommendations made by the CPT during its most recent visits to Switzerland, with a focus on prisons in French-speaking Switzerland, and also presents its workings in relation to the visits., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background: Pleural mesothelioma (MPM) is an aggressive malignancy with an average patient survival of only 10 months. Interestingly, about 5%-10% of the patients survive remarkably longer. Prior studies have suggested that the tumor immune microenvironment (TIME) has potential prognostic value in MPM. We hypothesized that high-resolution single-cell spatial profiling of the TIME would make it possible to identify subpopulations of patients with long survival and identify immunophenotypes for the development of novel treatment strategies., Methods: We used multiplexed fluorescence immunohistochemistry (mfIHC) and cell-based image analysis to define spatial TIME immunophenotypes in 69 patients with epithelioid MPM (20 patients surviving ≥ 36 months). Five mfIHC panels (altogether 21 antibodies) were used to classify tumor-associated stromal cells and different immune cell populations. Prognostic associations were evaluated using univariate and multivariable Cox regression, as well as combination risk models with area under receiver operating characteristic curve (AUROC) analyses., Results: We observed that type M2 pro-tumorigenic macrophages (CD163 + pSTAT1 - HLA-DRA1 - ) were independently associated with shorter survival, whereas granzyme B + cells and CD11c + cells were independently associated with longer survival. CD11c + cells were the only immunophenotype increasing the AUROC (from 0.67 to 0.84) when added to clinical factors (age, gender, clinical stage, and grade)., Conclusion: High-resolution, deep profiling of TIME in MPM defined subgroups associated with both poor (M2 macrophages) and favorable (granzyme B/CD11c positivity) patient survival. CD11c positivity stood out as the most potential prognostic cell subtype adding prediction power to the clinical factors. These findings help to understand the critical determinants of TIME for risk and therapeutic stratification purposes in MPM., 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 © 2022 Ollila, Mäyränpää, Paavolainen, Paajanen, Välimäki, Sutinen, Wolff, Räsänen, Kallioniemi, Myllärniemi, Ilonen and Pellinen.)

Carbon black nanoparticles (CBNPs) have a large surface area/volume ratio and are known to generate oxidative stress and inflammation that may result in genotoxicity and cancer. Here, we evaluated the primary and inflammatory response-driven (i.e. secondary) genotoxicity of two CBNPs, Flammruss101 (FL101) and PrintexXE2B (XE2B) that differ in size and specific surface area (SSA), and cause different amounts of reactive oxygen species. Three doses (low, medium and high) of FL101 and XE2B were assessed in vitro in the lung epithelial (A549) and activated THP-1 (THP-1a) monocytic cells exposed in submerged conditions for 6 and 24 h, and in C57BL/6 mice at day 1, 28 and 90 following intratracheal instillation. In vitro , we assessed pro-inflammatory response as IL-8 and IL-1β gene expression, and in vivo , inflammation was determined as inflammatory cell infiltrates in bronchial lavage (BAL) fluid and as histological changes in lung tissue. DNA damage was quantified in vitro and in vivo as DNA strand breaks levels by the alkaline comet assay. Inflammatory responses in vitro and in vivo correlated with dosed CBNPs SSA. Both materials induced DNA damage in THP-1a (correlated with dosed mass), and only XE2B in A549 cells. Non-statistically significant increase in DNA damage in vivo was observed in BAL cells. In conclusion, this study shows dosed SSA predicted inflammation both in vivo and in vitro , whereas dosed mass predicted genotoxicity in vitro in THP-1a cells. The observed lack of correlation between CBNP surface area and genotoxicity provides little evidence of inflammation-driven genotoxicity in vivo and in vitro .

Background: Our main objective was to provide estimates of the prevalence rates of psychiatric disorders and comorbidities among youths in a juvenile detention center in Geneva, Switzerland. We also aimed to investigate potential positive effects of intensive psychotherapeutic and educational services this center provides. Finally, we examined psychiatric care prior to and after custody as well as the evolution of the youths' mental health during detention. Methods: We conducted a longitudinal study including a group of incarcerated ( n = 86) and a group of non-incarcerated ( n = 169) youths (12-18 years old). Measures included diagnoses of psychiatric disorders, cognitive functions, trauma, psychopathic traits and the Youth Self-Report (aggressive behavior, attentional disorders, criminal behavior, social withdrawal, anxiety, depression and somatic complaints) collected at baseline and at discharge for the incarcerated group. Data were analyzed using mixed-effect models. Results: Psychiatric disorders were prevalent in the incarcerated group (82.6, 95% CI: 71.6-90.7%), but young people also often suffered from several disorders simultaneously. Two-thirds of the incarcerated participants had a diagnosis of two or more psychiatric disorders. Regarding health care, most incarcerated participants (79.1%) had psychiatric care prior to detention. The planned care after detention was associated with psychiatric comorbidities, care being more likely planned for those with comorbidities ( p = 0.030). Compared to the non-incarcerated group, the incarcerated group had lower scores on cognitive functioning ( p < 0.001) and higher scores on trauma ( p < 0.021) and psychopathic traits ( p < 0.034). The youths' stay in the detention center was associated with a positive change of mental health, with externalized problems being significantly reduced at the end of their stay ( p = 0.017). Conclusion: Our findings showed that youths in conflict with the law are characterized by (1) their internal vulnerabilities: a high prevalence of psychiatric disorders and psychiatric comorbidities, lower cognitive functions, externalized problems and psychopathic traits; (2) environmental factors: victims of violence and sexual abuse; and (3) their psychiatric history. Besides, the evolution of the most prevalent issues was favorable over time, which puts into question the usual perspective about the deleterious effect of detention., 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 © 2022 Heller, Morosan, Badoud, Laubscher, Jimenez Olariaga, Debbané, Wolff and Baggio.)

A part of the residents of nursing homes drink alcohol. This regularly leads to moral questions and discussions. An explorative qualitative study has been done to gather insight into the experiences and views of residents and staff regarding alcohol consumption in nursing homes. Aim of this publication was to support care professionals in nursing homes to deal with moral challenges related to alcohol consumption. With interviews and a focus group with residents and staff, experiences, values and moral dilemmas were collected. While residents viewed alcohol consumption as a private matter, opinions of staff were not uniform. Staff is confronted with various moral questions based on different values, such as Respect for Autonomy, Quality of Life, Authenticity and (collective) Safety. This study advises staff to use the value scheme in case of concrete moral questions as a tool to careful analyse which values and norms are at stake and balance what could be an appropriate response.

Sinonasal intestinal-type adenocarcinoma is strongly associated with hardwood dust exposure. Non-intestinal-type adenocarcinoma is a rarer and less well-known subtype considered not to be related with wood dust exposure. We determined the relative numbers of these two tumor types in 56 sinonasal adenocarcinoma patients in France and Finland, relating them with carefully assessed wood dust exposure histories. Diagnostic workup including immunohistochemistry for the intestinal markers CDX2 and CK20 indicated that the proportions of the two tumors differed significantly between France and Finland. In Finnish samples non-intestinal adenocarcinomas were more common than intestinal-type adenocarcinomas (12 non-intestinal vs. nine intestinal), while in the French samples the reverse was true (six non-intestinal vs. 29 intestinal). Such remarkably dissimilar occurrence of these tumors in France and Finland presumably reflects different pathogenetic circumstances in the two countries, and perhaps their different patterns of wood dust exposure. In France the main source of wood dust is from hardwoods. In Finland it is derived from softwoods. This is the first systematic comparison of the occurrence of intestinal-type adenocarcinoma and non-intestinal-type adenocarcinoma in two countries with different wood usage. It appears to be the first systematic study on differences in wood dust exposure between intestinal-type adenocarcinoma and non-intestinal-type adenocarcinoma.

Forgoing healthcare for economic reasons has been previously associated with adverse health outcomes, including a higher risk of hospitalization, a lower quality of life, and worse self-reported health. However, the exact cause-to-effect relation between forgoing healthcare and health-related outcomes has been insufficiently described. Here, we investigate the prospective health consequences of forgoing healthcare for economic reasons using data from "ReBus" (N = 400), a prospective study examining the health consequences of forgoing healthcare (Baseline: 2008-2013, Follow-up: 2014-2016). Using regression models, we explored the baseline determinants of forgoing healthcare, including socioeconomic, demographic, and pre-existing health-risk factors, and examined the associations between forgoing healthcare at baseline and health deterioration at follow-up, using highly pertinent biomarkers (glucose, glycated hemoglobin, lipids, blood pressure) and SF-36 questionnaire data. Low income, low occupation, low education, and smoking were associated with higher odds of forgoing healthcare at baseline. Forgoing healthcare for economic reasons at baseline was subsequently related to detrimental changes in glucose, high-density lipoprotein cholesterol (HDL), and blood pressure (BP) at follow-up, independently of baseline socioeconomic factors (Glucose-β = 0.19, 95%CI[0.03;0.34], HDL-β = -0.07, 95%CI[-0.14;0.01], BP-β = 3.30, 95%CI[-0.01;6.60]). Moreover, we found strong associations between forgoing healthcare and adverse SF-36 health scores at follow-up, with individuals forgoing healthcare systematically displaying worse health scores (6%-11% lower scores). For the first time, we show that forgoing healthcare for economic reasons predicts adverse health-related consequences 2-8 years later. Our findings shall further encourage the implementation of public health measures aimed at identifying individuals who forgo healthcare and preventing the adverse health consequences of unmet medical needs., 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., (© 2021 The Authors.)

Disadvantaged populations have an increased risk of suicide and suicide attempts because of the Covid-19 pandemic. To date, few studies focused on people living in detention, who have a high burden of mental health problems and are exposed to severe control measures. Our study investigated whether there was an increase in suicide attempts in prison. Data were collected in the largest Swiss pre-trial prison (Champ-Dollon) for the pre-pandemic and the pandemic periods. We identified a statistically significant 57%-increase of suicide attempts. Mitigation measures, access to mental health care, and access to vaccination are needed to protect this vulnerable population., (Copyright © 2021. Published by Elsevier B.V.)

During the first wave of the Covid-19 pandemic, access to health care was limited, and patients encountered important delays for scheduled appointments and care. Empirical data relying on patients' reports of forgoing health care are scarce. This study investigated Covid-19-related self-reports of forgoing health care in a sample of vulnerable outpatients in Geneva, Switzerland. We collected data from 1167 adult outpatients, including clinically vulnerable patients (with chronic diseases), geriatric patients (involved in a health care network for people aged 60 or older), and socially vulnerable patients (involved in a migrant health program or a mobile outpatient community care center) in June 2020. Data on sociodemographic factors, forgoing health care, and anti-SARS-CoV-2 antibodies were collected. Of the patients, 38.5% reported forgoing health care. Forgoing health care was more frequent for younger patients, women, patients with a low level of education, and patients with a chronic disease (p < .001). There was no significant association between the presence of anti-SARS-CoV-2 antibodies and forgoing health care (p = .983). As the decrease in routine management of patients might have important and unpredictable adverse health consequences, avoiding delayed health care is crucial., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Malignant pleural mesothelioma (MPM) has a rich stromal component containing mesenchymal fibroblasts. However, the properties and interplay of MPM tumor cells and their surrounding stromal fibroblasts are poorly characterized. Our objective was to spatially profile known mesenchymal markers in both tumor cells and associated fibroblasts and correlate their expression with patient survival. The primary study cohort consisted of 74 MPM patients, including 16 patients who survived at least 60 months. We analyzed location-specific tissue expression of seven fibroblast markers in clinical samples using multiplexed fluorescence immunohistochemistry (mfIHC) and digital image analysis. Effect on survival was assessed using Cox regression analyses. The outcome measurement was all-cause mortality. Univariate analysis revealed that high expression of secreted protein acidic and cysteine rich (SPARC) and fibroblast activation protein in stromal cells was associated with shorter survival. Importantly, high expression of platelet-derived growth factor receptor beta (PDGFRB) in tumor cells, but not in stromal cells, was associated with shorter survival (hazard ratio [HR] = 1.02, p < 0.001). A multivariable survival analysis adjusted for clinical parameters and stromal mfIHC markers revealed that tumor cell PDGFRB and stromal SPARC remained independently associated with survival (HR = 1.01, 95% confidence interval [CI] = 1.00-1.03 and HR = 1.05, 95% CI = 1.00-1.11, respectively). The prognostic effect of PDGFRB was validated with an artificial intelligence-based analysis method and further externally validated in another cohort of 117 MPM patients. In external validation, high tumor cell PDGFRB expression associated with shorter survival, especially in the epithelioid subtype. Our findings suggest PDGFRB and SPARC as potential markers for risk stratification and as targets for therapy., (© 2021 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd.)

The Arabidopsis AAA ATPase SKD1 is essential for ESCRT-dependent endosomal sorting by mediating the disassembly of the ESCRTIII complex in an ATP-dependent manner. In this study, we show that SKD1 localizes to messenger ribonucleoprotein complexes upon heat stress. Consistent with this, the interactome of SKD1 revealed differential interactions under normal and stress conditions and included membrane transport proteins as well as proteins associated with RNA metabolism. Localization studies with selected interactome proteins revealed that not only RNA associated proteins but also several ESCRTIII and membrane trafficking proteins were recruited to messenger ribonucleoprotein granules after heat stress., 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 © 2021 Wolff, Jakoby, Stephan, Koebke and Hülskamp.)

This article considers health and human rights implications for people deprived of liberty during the COVID-19 crisis. The health risks of incarceration for individual and community health, particularly in overcrowded and underresourced prisons and detention centers, are well known, but with the COVID-19 pandemic have become a public health emergency.Physical distancing in prisons is hardly manageable, and protective means are poor or lacking. Emergency releases have been shown to be feasible in terms of public safety but lack sustainability in reducing the number of people living in detention, and, globally, only a small proportion of them have been released. Without controlling the infection inside prisons, global efforts to tackle the spread of the disease may fail. People living in detention are not only more vulnerable to infection with COVID-19 but they are also especially vulnerable to human rights violations induced by inappropriate restrictions under the pretext of infection control. Therefore, alternatives for detention should be promoted and the number of incarcerated people radically decreased.This article calls on policymakers and all professionals involved in public health and criminal justice not to waste the opportunities provided by the crisis but to act now.

Background: Benzodiazepines are commonly prescribed in prisons amidst the controversies surrounding their potential role in causing behavioral disinhibition and aggressive behavior and their association with use and trafficking of illicit and addictive substances. The present study aimed to (1) ascertain the relationship between benzodiazepine prescription (including their dosage and duration of use) and aggressive behavior and behavioral disinhibition in prison and (2) investigate whether there was an association between benzodiazepine prescription, (including their dosage and duration of use) and using and trafficking illicit and addictive substances during imprisonment., Methods: Data were extracted from the electronic database of an "open" Swiss prison (n = 1206, 1379 measures) over a 5-year period (2010-2015). Measures included benzodiazepine prescription, duration of benzodiazepine use and mean dosage, and punishable behaviors (physical and verbal aggression, disinhibited but not directly aggressive behaviors, property damage or theft, substance-related offenses, and rule transgression). We assessed the relationship between benzodiazepine prescription and punishable behaviors after propensity score matching. Logistic regressions were also used to test the relationship of benzodiazepine use duration and dosage with punishable behaviors among participants who received benzodiazepines., Results: After propensity score matching, benzodiazepine prescription was not significantly associated with any punishable behavior. Among detained persons who took benzodiazepines, there was no significant association of dosage and duration of use with offenses involving illicit or addictive substance use or trafficking., Conclusions: Our study did not empirically support the occurrence of increased aggressive or disinhibited behaviors or increased risk of substance abuse in detained persons who received benzodiazepines in prison. This suggests a need to reconsider restrictions in prescribing benzodiazepines in the prison setting.

Toxicogenomics opens novel opportunities for hazard assessment by utilizing computational methods to map molecular events and biological processes. In this study, the transcriptomic and immunopathological changes associated with airway exposure to a total of 28 engineered nanomaterials (ENM) are investigated. The ENM are selected to have different core (Ag, Au, TiO 2 , CuO, nanodiamond, and multiwalled carbon nanotubes) and surface chemistries (COOH, NH 2 , or polyethylene glycosylation (PEG)). Additionally, ENM with variations in either size (Au) or shape (TiO 2 ) are included. Mice are exposed to 10 µg of ENM by oropharyngeal aspiration for 4 consecutive days, followed by extensive histological/cytological analyses and transcriptomic characterization of lung tissue. The results demonstrate that transcriptomic alterations are correlated with the inflammatory cell infiltrate in the lungs. Surface modification has varying effects on the airways with amination rendering the strongest inflammatory response, while PEGylation suppresses toxicity. However, toxicological responses are also dependent on ENM core chemistry. In addition to ENM-specific transcriptional changes, a subset of 50 shared differentially expressed genes is also highlighted that cluster these ENM according to their toxicity. This study provides the largest in vivo data set currently available and as such provides valuable information to be utilized in developing predictive models for ENM toxicity., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Treatment of locally advanced, unresectable head and neck squamous cell carcinoma (HNSCC) often yields only modest results with radiochemotherapy (RCT) as standard of care. Prognostic features related to outcome upon RCT might be highly valuable to improve treatment. Monocarboxylate transporters-1 and -4 (MCT1/MCT4) were evaluated as potential biomarkers. A cohort of HNSCC patients without signs for distant metastases was assessed eliciting 82 individuals eligible whereof 90% were diagnosed with locally advanced stage IV. Tumor specimens were stained for MCT1 and MCT4 in the cell membrane by immunohistochemistry. Obtained data were evaluated with respect to overall (OS) and progression-free survival (PFS). Protein expression of MCT1 and MCT4 in cell membrane was detected in 16% and 85% of the tumors, respectively. Expression of both transporters was not statistically different according to the human papilloma virus (HPV) status. Positive staining for MCT1 (n = 13, negative in n = 69) strongly worsened PFS with a hazard ratio (HR) of 3.1 (95%-confidence interval 1.6-5.7, p < 0.001). OS was likewise affected with a HR of 3.8 (2.0-7.3, p < 0.001). Multivariable Cox regression confirmed these findings. We propose MCT1 as a promising biomarker in HNSCC treated by primary RCT.

Objectives: To develop and validate a screening tool designed to identify detained people at increased risk for COVID-19 mortality, the COVID-19 Inmate Risk Appraisal (CIRA)., Design: Cross-sectional study with a representative sample (development) and a case-control sample (validation)., Setting: The two largest Swiss prisons., Participants: (1) Development sample: all male persons detained in Pöschwies, Zurich (n = 365); (2) Validation sample: case-control sample of male persons detained in Champ-Dollon, Geneva (n = 192, matching 1:3 for participants at risk for severe course of COVID-19 and participants without risk factors)., Main Outcome Measures: The CIRA combined seven risk factors identified by the World Health Organization and the Swiss Federal Office of Public Health as predictive of severe COVID-19 to derive an absolute risk increase in mortality rate: Age ≥60 years, cardiovascular disease, diabetes, hypertension, chronic respiratory disease, immunodeficiency and cancer., Results: Based on the development sample, we proposed a three-level classification: average (<3.7), elevated (3.7-5.7) and high (>5.7) risk. In the validation sample, the CIRA identified all individuals identified as vulnerable by national recommendations (having at least one risk factor). The category “elevated risk” maximised sensitivity (1) and specificity (0.97). The CIRA had even higher capacity in discriminating individuals vulnerable according to clinical evaluation (a four-level risk categorisation based on a consensus of medical staff). The category “elevated risk” maximised sensitivity and specificity (both 1). When considering the individuals classified as extremely high risk by medical staff, the category “high risk” had a high discriminatory capacity (sensitivity =0.89, specificity =0.97)., Conclusions: The CIRA scores have a high discriminative ability and will be important in custodial settings to support decisions and prioritise actions using a standardised valid assessment method. However, as knowledge on risk factors for COVID-19 mortality is still limited, the CIRA may be considered preliminary. Underlying data will be updated regularly on the website (http://www.prison-research.com), where the CIRA algorithm is freely available.

Materials can be modified for improved functionality. Our aim was to test whether pulmonary toxicity of silica nanomaterials is increased by the introduction of: a) porosity; and b) surface doping with CuO; and whether c) these modifications act synergistically. Mice were exposed by intratracheal instillation and for some doses also oropharyngeal aspiration to: 1) solid silica 100 nm; 2) porous silica 100 nm; 3) porous silica 100 nm with CuO doping; 4) solid silica 300 nm; 5) porous silica 300 nm; 6) solid silica 300 nm with CuO doping; 7) porous silica 300 nm with CuO doping; 8) CuO nanoparticles 9.8 nm; or 9) carbon black Printex 90 as benchmark. Based on a pilot study, dose levels were between 0.5 and 162 µg/mouse (0.2 and 8.1 mg/kg bw). Endpoints included pulmonary inflammation (neutrophil numbers in bronchoalveolar fluid), acute phase response, histopathology, and genotoxicity assessed by the comet assay, micronucleus test, and the gamma-H2AX assay. The porous silica materials induced greater pulmonary inflammation than their solid counterparts. A similar pattern was seen for acute phase response induction and histologic changes. This could be explained by a higher specific surface area per mass unit for the most toxic particles. CuO doping further increased the acute phase response normalized according to the deposited surface area. We identified no consistent evidence of synergism between surface area and CuO doping. In conclusion, porosity and CuO doping each increased the toxicity of silica nanomaterials and there was no indication of synergy when the modifications co-occurred.

Background: This study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases., Materials and Methods: A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019., Results: Questionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples., Conclusions: The COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe., Competing Interests: Disclosure The authors have declared no conflicts of interest. Data sharing Anonymized participant-level data are available for investigators. Ethical approval The study complied with the law of January 1978 (78-17) relating to computing, data, and freedom known as ‘computing and freedoms’ and with rules 2016/679 of the European Parliament (of 25 May 2018) concerning the general data protection regulation (GDPR; MR004). The study was registered by the Nice University Hospital (R04-39) and filed on the Health Data Hub website (7 July 2020) (www.health-data-hub.fr/depot)., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Photorhabdus spp. (Enterobacteriales: Morganellaceae) occur exclusively as symbionts of Heterorhabditis nematodes for which they provide numerous services, including killing insects and providing nutrition and defence within the cadavers. Unusually, two species (Photorhabdus cinerea and Photorhabdus temperata) associate with a single population of Heterorhabditis downesi at a dune grassland site. Building on previous work, we investigated competition between these two Photorhabdus species both at the regional (between insects) and local (within insect) level by trait comparison and co-culture experiments. There was no difference between the species with respect to supporting nematode reproduction and protection of cadavers against invertebrate scavengers, but P. cinerea was superior to P. temperata in several traits: faster growth rate, greater antibacterial and antifungal activity and colonisation of a higher proportion of nematodes in co-culture. Moreover, where both bacterial symbionts colonised single nematode infective juveniles, P. cinerea tended to dominate in numbers. Differences between Photorhabdus species were detected in the suite of secondary metabolites produced: P. temperata produced several compounds not produced by P. cinerea including anthraquinone pigments. Bioluminescence emitted by P. temperata also tended to be brighter than that from P. cinerea. Bioluminescence and pigmentation may protect cadavers against scavengers that rely on sight. We conclude that while P. cinerea may show greater local level (within-cadaver) competitive success, co-existence of the two Photorhabdus species in the spatially heterogeneous environment of the dunes is favoured by differing specialisations in defence of the cadaver against differing locally important threats.