Post-mortem tissue biopsies obtained at minimally invasive autopsy: An RNA-quality analysis

Introduction: Bereaved relatives often refuse to give consent for post-mortem investigation of deceased cancer patients, mainly because of the mutilation due to conventional au

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

To which world regions does the valence–dominance model of social perception apply?

Over the past 10 years, Oosterhof and Todorov’s valence–dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov’s methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov’s original analysis strategy, the valence–dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence–dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution.C.L. was supported by the Vienna Science and Technology Fund (WWTF VRG13-007); L.M.D. was supported by ERC 647910 (KINSHIP); D.I.B. and N.I. received funding from CONICET, Argentina; L.K., F.K. and Á. Putz were supported by the European Social Fund (EFOP-3.6.1.-16-2016-00004; ‘Comprehensive Development for Implementing Smart Specialization Strategies at the University of Pécs’). K.U. and E. Vergauwe were supported by a grant from the Swiss National Science Foundation (PZ00P1_154911 to E. Vergauwe). T.G. is supported by the Social Sciences and Humanities Research Council of Canada (SSHRC). M.A.V. was supported by grants 2016-T1/SOC-1395 (Comunidad de Madrid) and PSI2017-85159-P (AEI/FEDER UE). K.B. was supported by a grant from the National Science Centre, Poland (number 2015/19/D/HS6/00641). J. Bonick and J.W.L. were supported by the Joep Lange Institute. G.B. was supported by the Slovak Research and Development Agency (APVV-17-0418). H.I.J. and E.S. were supported by a French National Research Agency ‘Investissements d’Avenir’ programme grant (ANR-15-IDEX-02). T.D.G. was supported by an Australian Government Research Training Program Scholarship. The Raipur Group is thankful to: (1) the University Grants Commission, New Delhi, India for the research grants received through its SAP-DRS (Phase-III) scheme sanctioned to the School of Studies in Life Science; and (2) the Center for Translational Chronobiology at the School of Studies in Life Science, PRSU, Raipur, India for providing logistical support. K. Ask was supported by a small grant from the Department of Psychology, University of Gothenburg. Y.Q. was supported by grants from the Beijing Natural Science Foundation (5184035) and CAS Key Laboratory of Behavioral Science, Institute of Psychology. N.A.C. was supported by the National Science Foundation Graduate Research Fellowship (R010138018). We acknowledge the following research assistants: J. Muriithi and J. Ngugi (United States International University Africa); E. Adamo, D. Cafaro, V. Ciambrone, F. Dolce and E. Tolomeo (Magna Græcia University of Catanzaro); E. De Stefano (University of Padova); S. A. Escobar Abadia (University of Lincoln); L. E. Grimstad (Norwegian School of Economics (NHH)); L. C. Zamora (Franklin and Marshall College); R. E. Liang and R. C. Lo (Universiti Tunku Abdul Rahman); A. Short and L. Allen (Massey University, New Zealand), A. Ateş, E. Güneş and S. Can Özdemir (Boğaziçi University); I. Pedersen and T. Roos (Åbo Akademi University); N. Paetz (Escuela de Comunicación Mónica Herrera); J. Green (University of Gothenburg); M. Krainz (University of Vienna, Austria); and B. Todorova (University of Vienna, Austria). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.https://www.nature.com/nathumbehav/am2023BiochemistryGeneticsMicrobiology and Plant Patholog

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities

Atypical presentation of COVID-19 in older patients is associated with frailty but not with adverse outcomes

Purpose: Older patients with COVID-19 can present with atypical complaints, such as falls or delirium. In other diseases, such an atypical presentation is associated with worse clinical outcomes. However, it is not known whether this extends to COVID-19. We aimed to study the association between atypical presentation of COVID-19, frailty and adverse outcomes, as well as the incidence of atypical presentation. Methods: We conducted a retrospective observational multi-center cohort study in eight hospitals in the Netherlands. We included patients aged ≥ 70 years hospitalized with COVID-19 between February 2020 until May 2020. Atypical presentation of COVID-19 was defined as presentation without fever, cough and/or dyspnea. We collected data concerning symptoms on admission, demographics and frailty parameters [e.g., Charlson Comorbidity Index (CCI) and Clinical Frailty Scale (CFS)]. Outcome data included Intensive Care Unit (ICU) admission, discharge destination and 30-day mortality. Results: We included 780 patients, 9.5% (n = 74) of those patients had an atypical presentation. Patients with an atypical presentation were older (80 years, IQR 76–86 years; versus 79 years, IQR 74–84, p = 0.044) and were more often classified as severely frail (CFS 6–9) compared to patients with a typical presentation (47.6% vs 28.7%, p = 0.004). Overall, there was no significant difference in 30-day mortality between the two groups in univariate analysis (32.4% vs 41.5%; p = 0.173) or in multivariate analysis [OR 0.59 (95% CI 0.34–1.0); p = 0.058]. Conclusions: In this study, patients with an atypical presentation of COVID-19 were more frail compared to patients with a typical presentation. Contrary to our expectations, an atypical presentation was not associated with worse outcomes.</p

Atypical presentation of COVID-19 in older patients is associated with frailty but not with adverse outcomes

Purpose: Older patients with COVID-19 can present with atypical complaints, such as falls or delirium. In other diseases, such an atypical presentation is associated with worse clinical outcomes. However, it is not known whether this extends to COVID-19. We aimed to study the association between atypical presentation of COVID-19, frailty and adverse outcomes, as well as the incidence of atypical presentation. Methods: We conducted a retrospective observational multi-center cohort study in eight hospitals in the Netherlands. We included patients aged ≥ 70 years hospitalized with COVID-19 between February 2020 until May 2020. Atypical presentation of COVID-19 was defined as presentation without fever, cough and/or dyspnea. We collected data concerning symptoms on admission, demographics and frailty parameters [e.g., Charlson Comorbidity Index (CCI) and Clinical Frailty Scale (CFS)]. Outcome data included Intensive Care Unit (ICU) admission, discharge destination and 30-day mortality. Results: We included 780 patients, 9.5% (n = 74) of those patients had an atypical presentation. Patients with an atypical presentation were older (80 years, IQR 76–86 years; versus 79 years, IQR 74–84, p = 0.044) and were more often classified as severely frail (CFS 6–9) compared to patients with a typical presentation (47.6% vs 28.7%, p = 0.004). Overall, there was no significant difference in 30-day mortality between the two groups in univariate analysis (32.4% vs 41.5%; p = 0.173) or in multivariate analysis [OR 0.59 (95% CI 0.34–1.0); p = 0.058]. Conclusions: In this study, patients with an atypical presentation of COVID-19 were more frail compared to patients with a typical presentation. Contrary to our expectations, an atypical presentation was not associated with worse outcomes.</p

Atypical presentation of COVID-19 in older patients is associated with frailty but not with adverse outcomes

Purpose: Older patients with COVID-19 can present with atypical complaints, such as falls or delirium. In other diseases, such an atypical presentation is associated with worse clinical outcomes. However, it is not known whether this extends to COVID-19. We aimed to study the association between atypical presentation of COVID-19, frailty and adverse outcomes, as well as the incidence of atypical presentation. Methods: We conducted a retrospective observational multi-center cohort study in eight hospitals in the Netherlands. We included patients aged ≥ 70 years hospitalized with COVID-19 between February 2020 until May 2020. Atypical presentation of COVID-19 was defined as presentation without fever, cough and/or dyspnea. We collected data concerning symptoms on admission, demographics and frailty parameters [e.g., Charlson Comorbidity Index (CCI) and Clinical Frailty Scale (CFS)]. Outcome data included Intensive Care Unit (ICU) admission, discharge destination and 30-day mortality. Results: We included 780 patients, 9.5% (n = 74) of those patients had an atypical presentation. Patients with an atypical presentation were older (80 years, IQR 76–86 years; versus 79 years, IQR 74–84, p = 0.044) and were more often classified as severely frail (CFS 6–9) compared to patients with a typical presentation (47.6% vs 28.7%, p = 0.004). Overall, there was no significant difference in 30-day mortality between the two groups in univariate analysis (32.4% vs 41.5%; p = 0.173) or in multivariate analysis [OR 0.59 (95% CI 0.34–1.0); p = 0.058]. Conclusions: In this study, patients with an atypical presentation of COVID-19 were more frail compared to patients with a typical presentation. Contrary to our expectations, an atypical presentation was not associated with worse outcomes

Benchmarking organic micropollutants in wastewater, recycled water and drinking water with in vitro bioassays

Thousands of organic micropollutants and their transformation products occur in water. Although often present at low concentrations, individual compounds contribute to mixture effects. Cell-based bioassays that target health-relevant biological endpoints may therefore complement chemical analysis for water quality assessment. The objective of this study was to evaluate cell-based bioassays for their suitability to benchmark water quality and to assess efficacy of water treatment processes. The selected bioassays cover relevant steps in the toxicity pathways including induction of xenobiotic metabolism, specific and reactive modes of toxic action, activation of adaptive stress response pathways and system responses. Twenty laboratories applied 103 unique in vitro bioassays to a common set of 10 water samples collected in Australia, including wastewater treatment plant effluent, two types of recycled water (reverse osmosis and ozonation/activated carbon filtration), stormwater, surface water, and drinking water. Sixty-five bioassays (63%) showed positive results in at least one sample, typically in wastewater treatment plant effluent, and only five (5%) were positive in the control (ultrapure water). Each water type had a characteristic bioanalytical profile with particular groups of toxicity pathways either consistently responsive or not responsive across test systems. The most responsive health-relevant endpoints were related to xenobiotic metabolism (pregnane X and aryl hydrocarbon receptors), hormone-mediated modes of action (mainly related to the estrogen, glucocorticoid, and antiandrogen activities), reactive modes of action (genotoxicity) and adaptive stress response pathway (oxidative stress response). This study has demonstrated that selected cell-based bioassays are suitable to benchmark water quality and it is recommended to use a purpose-tailored panel of bioassays for routine monitoring