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- Ruiz, Mario, 1984, et al.
(författare)
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A small molecule screen for paqr-2 suppressors identifies Tyloxapol as a membrane fluidizer for C. elegans and mammalian cells
- 2022
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Ingår i: Biochimica Et Biophysica Acta-Biomembranes. - : Elsevier BV. - 0005-2736. ; 1864:9
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Tidskriftsartikel (refereegranskat)abstract
- Defects in cell membrane homeostasis are implicated in numerous disorders, including cancer, neurodegeneration and diabetes. There is therefore a need for a powerful model to study membrane homeostasis and to identify eventual therapeutic routes. The C. elegans gene paqr-2 encodes a homolog of the mammalian AdipoR1 and AdipoR2 proteins that, when mutated, causes a membrane homeostasis defect accompanied by multiple phenotypes such as intolerance to dietary saturated fatty acids, intolerance to cold and a characteristic tail tip morphology defect. We screened a compound library to identify molecules that can suppress the paqr-2 phenotypes. A single positive hit, Tyloxapol, was found that very effectively suppresses multiple paqr-2 phenotypes. Tyloxapol is a non-ionic detergent currently in use clinically as an expectorant. Importantly, we examined the potential of Tyloxapol as a fluidizer in human cells and found that it improves the viability and membrane fluidity of AdipoR2-deficient human cells challenged with palmitic acid, a membrane-rigidifying saturated fatty acid.
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| 2. |
- Svensk, Erik, et al.
(författare)
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Limitations of care and comorbidities are associated with increased mortality in patients treated with non-invasive ventilation : a retrospective observational study in a single-center ICU
- 2021
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Ingår i: F1000 Research. - : F1000 Research Ltd. - 2046-1402. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Non-invasive ventilation (NIV) is a common treatment for acute respiratory failure in intensive care units (ICU). While there is increasing data on outcomes after NIV treatment, there are large variations in staffing and monitoring where NIV is provided, making results hard to generalize. The aim of this study was to characterize patients treated with NIV, describe outcomes, and identify factors associated with outcome in an ICU at a Swedish county hospital.Methods: A single-centre retrospective observational study during 2018 of patients treated with NIV in a six-bed ICU at a Swedish county hospital. Patient characteristics, including comorbidities, details of ICU stay, simplified acute physiology score (SAPS-3), details of NIV treatment and 30-day mortality were collected, and the Charlson co-morbidity index (CCI) was calculated. Primary outcomes were 30-day mortality and associated factors.Results: 92 patients with mean age (71,3, SD 12,1) were treated with NIV during the study period. 42 (46%) were women. Median CCI was 3 (25th-75th percentiles 1.4)) and median SAPS-3 score was 66 (25th-75th percentiles 58). The 30-day mortality was 37% and in the univariate analysis, SAPS-3 score >66, Charlson comorbidity index, CCI>=3, pCO2 <5.5 and limitation of care were factors associated with increased 30-day mortality. pH <7.35 and pO2<8 at admission showed no associations with 30-day mortality.Conclusions: We found that patients treated with NIV in ICU were a diverse population where comorbidities and presence of limitations of care might be considered as better predictors of 30-day mortality, rather than physiological parameters.
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