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Summary: Mitochondrial function relies on the coordinated transcription of mitochondrial and nuclear genomes to assemble respiratory chain complexes. Across species, the SIN3 coregulator influences mitochondrial functions, but how its loss impacts mitochondrial homeostasis and metabolism in the context of a whole organism is unknown. Exploring this link is important because SIN3 haploinsufficiency causes intellectual disability/autism syndromes and SIN3 plays a role in tumor biology. Here we show that loss of C. elegans SIN-3 results in transcriptional deregulation of mitochondrial- and nuclear-encoded mitochondrial genes, potentially leading to mito-nuclear imbalance. Consistent with impaired mitochondrial function, sin-3 mutants show extensive mitochondrial fragmentation by transmission electron microscopy (TEM) and in vivo imaging, and altered oxygen consumption. Metabolomic analysis of sin-3 mutant animals revealed a mitochondria stress signature and deregulation of methionine flux, resulting in decreased S-adenosyl methionine (SAM) and increased polyamine levels. Our results identify SIN3 as a key regulator of mitochondrial dynamics and metabolic flux, with important implications for human pathologies.

Molecular networking has become a key method to visualize and annotate the chemical space in non-targeted mass spectrometry data. We present feature-based molecular networking (FBMN) as an analysis method in the Global Natural Products Social Molecular Networking (GNPS) infrastructure that builds on chromatographic feature detection and alignment tools. FBMN enables quantitative analysis and resolution of isomers, including from ion mobility spectrometry.

Metabolism is one of the attributes of life and supplies energy and building blocks to organisms. Therefore, understanding metabolism is crucial for the understanding of complex biological phenomena. Despite having been in the focus of research for centuries, our picture of metabolism is still incomplete. Metabolomics, the systematic analysis of all small molecules in a biological system, aims to close this gap. In order to facilitate such investigations a blueprint of the metabolic network is required. Recently, several metabolic network reconstructions for the model organism Caenorhabditis elegans have been published, each having unique features. We have established the WormJam Community to merge and reconcile these (and other unpublished models) into a single consensus metabolic reconstruction. In a series of workshops and annotation seminars this model was refined with manual correction of incorrect assignments, metabolite structure and identifier curation as well as addition of new pathways. The WormJam consensus metabolic reconstruction represents a rich data source not only for in silico network-based approaches like flux balance analysis, but also for metabolomics, as it includes a database of metabolites present in C. elegans, which can be used for annotation. Here we present the process of model merging, correction and curation and give a detailed overview of the model. In the future it is intended to expand the model toward different tissues and put special emphasizes on lipid metabolism and secondary metabolism including ascaroside metabolism in accordance to their central role in C. elegans physiology.

Blood microsampling (BµS) offers an alternative to conventional methods that use plasma or serum for profiling human health, being minimally invasive and cost effective, especially beneficial for vulnerable populations. We present a non‐systematic review that offers a synopsis of the analytical methods, applications and perspectives related to dry blood microsampling in targeted and untargeted metabolomics and lipidomics research in the years 2022 and 2023. BµS shows potential in neonatal and paediatric studies, therapeutic drug monitoring, metabolite screening, biomarker research, sports supervision, clinical disorders studies and forensic toxicology. Notably, dried blood spots and volumetric absorptive microsampling options have been more extensively studied than other volumetric technologies. Therefore, we suggest that a further investigation and application of the volumetric technologies will contribute to the use of BµS as an alternative to conventional methods. Conversely, we support the idea that harmonisation of the analytical methods when using BµS would have a positive impact on its implementation. [ABSTRACT FROM AUTHOR]

Introduction: Massive pulmonary embolism (MPE) is a rare but highly fatal condition. Our study's objective was to evaluate the association between advanced interventions and survival among patients with MPE treated with venoarterial extracorporeal membrane oxygenation (VA-ECMO). Methods: This is a retrospective review of the Extracorporeal Life Support Organization (ELSO) registry data. We included adult patients with MPE who were treated with VA-ECMO during 2010–2020. Our Primary outcome was survival to hospital discharge; secondary outcomes were ECMO duration among survivors and rates of ECMO-related complications. Clinical variables were compared using the Pearson chi-square and Kruskal-Wallis H tests. Results: We included 802 patients; 80 (10%) received SPE and 18 (2%) received CDT. Overall, 426 (53%) survived to discharge; survival was not significantly different among those treated with SPE or CDT on VA-ECMO (70%) versus VA-ECMO alone (52%) or SPE or CDT before VA-ECMO (52%). Multivariable regression found a trend towards increased survival among those treated with SPE or CDT while on ECMO (AOR 1.8, 95% CI 0.9–3.6), but no significant correlation. There was no association between advanced interventions and ECMO duration among survivors, or rates of ECMO-related complications. Conclusion: Our study found no difference in survival in patients with MPE who received advanced interventions prior to ECMO, and a slight non-significant benefit in those who received advanced interventions while on ECMO. [ABSTRACT FROM AUTHOR]

Introduction: Our goal was to evaluate patients’ threshold for waiting in an emergency department(ED) waiting room before leaving without being seen (LWBS). We analyzed whether willingness towait was influenced by perceived illness severity, age, race, triage acuity level, or insurance status.Methods: We conducted this survey-based study from March to July 2010 at an urban academicmedical center. After triage, patients were given a multiple-choice questionnaire, designed toascertain how long they would wait for medical care. We collected data including age, gender, race,insurance status, and triage acuity level. We looked at the association between willingness to waitand these variables, using stratified analysis and logistic regression.Results: Of the 375 patients who were approached, 340 (91%) participated. One hundred seventyone(51%) were willing to wait up to 2 hours before leaving, 58 (17%) would wait 2 to 8 hours, and110 (32%) would wait indefinitely. No association was found between willingness to wait and race,gender, insurance status, or perceived symptom severity. Patients willing to wait >2 hours tended tobe older than 25, have higher acuity, and prefer the study site ED.Conclusion: Many patients have a defined, limited period that they are willing to wait for emergencycare. In our study, 50% of patients were willing to wait up to 2 hours before leaving the ED withoutbeing seen. This result suggests that efforts to reduce the percentage of patients who LWBS mustfactor in time limits. [West J Emerg Med. 2012;13(6):463-467]