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Hacking Death in Dublin.
Gastroenterology
January 2025
End of Life Studies Group, School of Social and Environmental Sustainability, University of Glasgow, Dumfries Campus, Dumfries, United Kingdom.
Interplay between the SAFE and the sphingolipid pathway for cardioprotection.
Life Sci
December 2024
Hatter Institute/Cape Heart Institute, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. Electronic address:
Aim: Activation of both the Survivor Activating Factor Enhancement (SAFE) pathway (including Tumor Necrosis Factor-alpha (TNF-α) and Signal Transducer and Activator of Transcription-3 (STAT-3)) and the sphingolipid signalling pathway (including sphingosine kinase-1 (SK1) and sphingosine-1 phosphate (S1P)) play a key role in promoting cardioprotection against ischemia-reperfusion injury (IRI). We investigated whether the activation of the SAFE pathway by exogenous S1P is dependent on the activation of SK1 for cardioprotection.
Materials And Methods: Isolated cardiomyocytes from TNF-α knockout (KO) mice, cardiomyocyte-specific STAT-3 KO mice and their wild-type (WT) littermates were exposed to simulated ischemia in the presence of a trigger of the SAFE pathway (S1P) and SK1 inhibitor (SK1-I).
Hacking the Lipidome: New Ferroptosis Strategies in Cancer Therapy.
Biomedicines
February 2024
Genetics and Cellular Engineering Group, Research Unit Signaling and Translation, Helmholtz Zentrum Munich, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany.
The concept of redirecting metabolic pathways in cancer cells for therapeutic purposes has become a prominent theme in recent research. Now, with the advent of ferroptosis, a new chink in the armor has evolved that allows for repurposing of ferroptosis-sensitive lipids in order to trigger cell death. This review presents the historical context of lipidomic and metabolic alterations in cancer cells associated with ferroptosis sensitization.
View Article and Find Full Text PDFMild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest.
N Engl J Med
July 2023
From the Departments of Intensive Care (G.E., L.P., R.B.) and Neurology (J.A.), Austin Hospital, the Australian and New Zealand Intensive Care Research Centre (G.E., A.D.N., C.H., S.M., G.C., M.J.B., E.P., B.A., T.T., R.B.), the School of Public Health and Preventive Medicine, Monash University (S.B., D.S.), the Departments of Intensive Care (C.H., S.B., T.T.) and Cardiology (D.S.), Alfred Hospital, the Division of Critical Care (C.H., R.B.) and the Departments of Medicine (J.A.) and Critical Care (A.D.), University of Melbourne, the Department of Intensive Care, Royal Melbourne Hospital (A.D., R.B.), and the Department of Intensive Care, Northern Hospital (A.G.), Melbourne, VIC, the Division of Critical Care, George Institute for Global Health, Sydney (C.H.), and the Intensive Care Unit, Princess Alexandra Hospital, and the School of Medicine, University of Queensland, Brisbane (J.W.) - all in Australia; the Clinical Research Centre at St. Vincent's Hospital, University College Dublin, Dublin (A.D.N., K.A., S.M., C.F.); the Cardiothoracic and Vascular Intensive Care Unit (R.L.P., S.M.) and the Department of Critical Care Medicine (Y.W.C.), Auckland City Hospital, and the School of Nursing, University of Auckland (R.L.P.), Auckland, Intensive Care Research (A.H.), Medical Research Institute of New Zealand (R.L.P., S.M.), and the Intensive Care Unit, Wellington Regional Hospital (E.L.), Wellington, and the Department of Intensive Care, Christchurch Hospital, Canterbury (D.K.) - all in New Zealand; the Sections of Anesthesiology and Intensive Care (N.N., J.D.), Cardiology (J.D.), and Neurology (G. Lilja, T.C.), Department of Clinical Sciences, Lund University, Skåne University Hospital, Lund, Helsingborg Hospital, Helsingborg (N.N.), and the Department of Anesthesia and Intensive Care Medicine, Skåne University Hospital, Malmo (J.P.D.) - all in Sweden; the Departments of Emergency Care and Services (M.B.S.) and Intensive Care (M.B.), Helsinki University Hospital and University of Helsinki, and the Department of Neurology, Helsinki University Hospital (M. Tiainen) - all in Helsinki; the Department of Intensive Care, Hôpital Universitaire de Bruxelles-Université Libre de Bruxelles (F.S.T.), and the Department of Intensive Care, Erasme University Hospital (F.A.) - both in Brussels; the Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada (D.K.); the Emergency Department and Department of Clinical Medicine, Aarhus University Hospital and Aarhus University (H.K.), the Departments of Intensive Care Medicine (A.M.G., S.C., H.M.-A.) and Anesthesiology and Intensive Care (A.G.), Aarhus University Hospital, and the Department of Clinical Medicine, Aarhus University (A.M.G.) - all in Aarhus, Denmark; Reanimation Medicale, Centre Hospitalier Universitaire, Franche-Comte, Unité de Formation et de Recherche Santé, University of Franche-Comte, Besançon, France (G.C.); the Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, and the School of Medicine, Vita-Salute San Raffaele University, Milan (G. Landoni); the Department of Intensive Care, Amsterdam University Medical Centers, Amsterdam (J.H.); the Department of Anesthesiology and Intensive Care Medicine, Institute of Clinical Medicine, University of Oslo (T.O.), and the Department of Cardiology, Oslo University Hospital-Ullevål (G.Ø.A., E.Q., A.F.) - both in Oslo; the Intensive Care Department, Ministry of National Guard Health Affairs, the College of Medicine, King Saud bin Abdulaziz University Hospital for Health Sciences, and King Abdullah International Medical Research Center - all in Riyadh, Saudi Arabia (Y.A., H.T.); the Cardiology Department, Tan Tock Seng Hospital, the School of Medicine, National University of Singapore Yong Loo Lin School of Medicine, and the Department of Medicine, Nanyang Technological University Lee Kong Chian School of Medicine - all in Singapore (Y.W.C.); the Department of Internal Intensive Medicine, University Medical Center Maribor, Maribor, Slovenia (A.M., F.S.); the Department of Intensive Care Medicine, Bern University Hospital (M.H.), and the Departments of Intensive Care Medicine (M.I.) and Anesthesiology and Pain Medicine (A.L.), Inselspital, Bern University Hospital, University of Bern, Bern, and the Institute of Intensive Care Medicine, University Hospital of Zurich, Zurich (M.P.H.) - all in Switzerland; and the Department of Adult Critical Care, University Hospital of Wales, Cardiff (M.P.W., J.C.), the Intensive Care Unit, Bristol Royal Infirmary, Bristol (M. Thomas, K.S., J.B.), the Regional Intensive Care Unit, Royal Victoria Hospital (P.J.M.), and the Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast (P.J.M.), Belfast, and the Academic Department of Critical Care, Queen Alexandra Hospital, Portsmouth (D.P.) - all in the United Kingdom.
Article Synopsis
- Guidelines suggest maintaining normal carbon dioxide levels for adults in a coma resuscitated from cardiac arrest, but mild higher levels may help increase brain blood flow and improve outcomes.
- In a study involving 1,700 patients, participants were randomly assigned to either mild hypercapnia or normocapnia for 24 hours and were assessed 6 months later for neurologic recovery.
- Results showed no significant difference in favorable neurological outcomes or mortality between the two groups, indicating that mild hypercapnia did not improve recovery compared to normal levels.
Triple-negative Breast Carcinoma With Apocrine and Histiocytoid Features: A Clinicopathologic and Molecular Study of 18 Cases.
Am J Surg Pathol
September 2023
Departments of Pathology and Laboratory Medicine.
Article Synopsis
- Triple-negative breast cancer (TNBC) is a diverse group of tumors, with most being aggressive high-grade types, but a minority classified as non-high-grade and exhibiting less aggressive behavior.
- A study examined 18 non-high-grade TNBCs, mostly with apocrine features, and found that they had low Ki-67 levels, with only 11% showing lymph node metastasis and no recurrences during an average follow-up of 38 months.
- The tumors showed distinct genetic profiles, particularly involving the PI3K-PKB/Akt and RTK-RAS pathways, indicating that non-high-grade TNBCs are a unique subgroup with specific clinical behaviors that may require tailored treatment approaches.
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