University of Zurich

Lead (Pb) poisoning remains a global public health challenge, yet approved chelating agents are limited by poor selectivity, suboptimal efficacy, and safety concerns. We previously reported cyclic tetrapeptides as metal-binding therapeutics for Pb detoxification. The lead scaffold, containing two cysteines and two β-aspartic acid residues, showed high aqueous solubility but failed to rescue Pb-poisoned human cells. In this work, we conducted mechanistic studies revealing that diminished intrinsic Pb(ii) affinity and poor selectivity against competing Ca(ii) ions constrained its activity. Guided by these insights, we synthesized two analogs: one lacking a carboxylate and another with an inverted chiral center. Both analogs demonstrated markedly improved Pb detoxification in human cells, surpassing the efficacy of clinically used chelators. Strikingly, oral administration of the diastereomeric analog to Pb-exposed mice lowered blood Pb levels by 55-62% and increased urinary Pb excretion by up to 3-fold compared with vehicle or standard-of-care treatments. These findings illustrate how rational structure-activity relationship optimization can deliver selective, effective peptide-based chelators, establishing a promising therapeutic strategy against Pb poisoning.

Postmortem interval (PMI) estimation is a critical component of forensic investigations as it can help establish a timeline of events and assist in reducing a pool of missing persons or potential suspects. Despite its importance, the accuracy of PMI estimation remains challenging due to the complexity of decomposition and limitations of current methods, particularly in the later postmortem period. Proteomics has shown potential as a more objective method, with current studies taking an untargeted approach to identify informative peptide targets. Previous studies in our laboratory analysed human muscle tissue and identified 12 peptide ratios, consisting of 19 individual peptides, that were correlated with decomposition time. This study aimed to optimise the detection of these 19 peptide targets using a targeted liquid chromatography triple quadrupole mass spectrometry (LC-QQQ) method suited for casework applications and instrument platforms commonly found in forensic laboratories. Of the 19 peptide targets, 17 were optimised to be reproducible. Additionally, a longitudinal analysis in authentic human samples was conducted over a 14-day period postmortem to monitor detection throughout the decomposition process. All but one of the targets produced interpretable results, and data analysis was performed to generate peptide ratios. After log2 transformation, two of the previously proposed peptide ratios showed linear trends. Overall, this study has shown that a targeted LC-QQQ method is a viable system for the detection of PMI peptide targets from human postmortem muscle tissue and has demonstrated the potential for this type of analysis to be validated and applied in routine forensic casework.

In a follow up to a previous paper [6], this article continues the exploration of fibres recovered from the respiratory tract in smothering cases. Specifically, this second part examines the transfer of fibres when smothering has occurred as compared to legitimate exposures to the textile in question. In order to simulate these activities, volunteers breathed through textiles of various levels of shedding under conditions of strain and at rest. Fibres were then self-recovered from the nose and mouth for the counting of target fibres that have transferred. The results demonstrate a noticeable difference between the two activities in terms of the quantity of fibres transferred. This difference is increasingly marked for higher levels of shedding. The findings from this paper and from part 1 were then utilized to assign probabilities which were subsequently used to evaluate findings of two hypothetical scenarios meant to represent commonly encountered case disputed issues. The results further highlight the potential for such traces to aid in suspected smothering cases. In general, low number of fibres (<5) support propositions of non-smothering whereas larger quantities (>15) typically support those of smothering. The count of fibres at which the support switches is highly dependent on the shedding of the textile. It is thus important to consider shedding and the quantity of fibres recovered in such cases.

Understanding how media influence public attitudes toward science during societal challenges is crucial for effective science communication. This study examines the role of media use and sociodemographic factors in shaping public attitudes toward science in Switzerland using panel data from three surveys over 6 years (N2016 = 1,051; N2019 = 339; N2022 = 122). Results show that media usage and sociodemographics influenced attitudes, especially during the COVID-19 pandemic. Lower education and stronger religiosity correlated with reduced interest in or trust in science. Use of online legacy media showed rally-around-the-flag effects, but we found no clear differences between public and private broadcasters regarding their impact on science attitudes. These findings highlight the relationship of media use, sociodemographics, and public attitudes during societal uncertainty and over time, offering insights for targeted, context-sensitive science communication.

Hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome is a rare pediatric epilepsy syndrome characterized by prolonged focal febrile seizures, postictal hemiparesis, and progressive unilateral brain injury, often followed by chronic epilepsy. We report a previously healthy 10-month-old girl who presented with a prolonged left-sided focal fever-associated seizure. She tested positive for SARS-CoV-2 but did not meet criteria for multisystem inflammatory syndrome in children. On admission, she had left-sided flaccid hemiparesis. Brain MRI showed mild diffusion restriction and marked hyperperfusion of the right hemispheric gray matter, most prominently in the frontal, temporo-occipital, and hippocampal regions. EEG showed high-amplitude slowing over the right hemisphere without epileptiform discharges. No further seizures occurred, and long-term antiseizure treatment was not required. At 9-month follow-up, the patient was seizure-free and developmentally age-appropriate, but the hemiparesis persisted. Serial MRI showed progressive right hemispheric cortical and subcortical atrophy and hippocampal sclerosis. Extensive diagnostic workup found no other structural, infectious, or metabolic cause. This case illustrates the classical biphasic course of HHE syndrome and highlights the diagnostic value of early MRI, EEG, and genetic testing. The patient carried a paternally inherited heterozygous IRF3 variant, a gene essential for innate antiviral immunity. Although causality cannot be established, the temporal association with SARS-CoV-2 infection and an IRF3 variant suggests a possible genetic predisposition to infection-triggered injury. Continued clinical vigilance and long-term follow-up are essential, as epilepsy develops in most children with HHE. Greater awareness of this syndrome may support earlier recognition and timely rehabilitation to optimize functional outcomes.

Noninvasive neuromonitoring provides valuable insights into cerebral physiology and function, with the potential to support individualized care for patients who are critically ill. As precision medicine continues to advance within the intensive care unit, the integration of multiple noninvasive monitoring techniques may offer a more comprehensive, real-time understanding of dynamic cerebral pathophysiology while avoiding the risks of invasive procedures. This study aimed to identify the implementation challenges of combining multiple noninvasive neuromonitoring modalities. Six modalities were selected: blind transcranial Doppler ultrasonography, optic nerve sheath diameter measurement, multichannel continuous electroencephalography (cEEG), automated pupillometry, near-infrared spectroscopy (NIRS), and skull extensometer (Brain4Care). To assess the readiness of each modality for integration into a multimodal noninvasive monitoring setup, a group of experts propose the Noninvasive Neuromonitoring Multimodal Readiness (nnMR) score. This scoring system aims to provide a structured evaluation of each modality's multimodal suitability based on criteria such as data continuity and processing, physiological signal representation, spatial and temporal resolution, and software integration in the intensive care unit setting. nnMR scores showed that cEEG and NIRS enable continuous monitoring without manual processing. Blind transcranial Doppler and NIRS offer a good temporal resolution; optic nerve sheath diameter provides good spatial resolution; cEEG and skull extensometer combine both. Only cEEG demonstrates anatomical clarity. Software integration remains limited across all modalities. Key challenges to multimodal implementation include the need for skilled personnel, artifact susceptibility, mismatched temporal and spatial resolutions, and limited long-term signal stability. Integration into unified analytical platforms is further constrained by a lack of standardization, requiring separate manual data input, processing, and quantification. The nnMR score was developed to assess the current readiness of each modality for multimodal, continuous, and long-term clinical application. To validate the proposed nnMR score, engagement with the broader neurocritical care community is essential. Realizing the full potential of multimodal neuromonitoring will require advances in signal validation, software integration, resolution alignment, artifact detection, fixation techniques, and standardization, necessitating close collaboration among researchers, engineers, manufacturers, and clinicians.