Background: Although pregnancy is expected during studies of novel contraceptives in non-human primates, gestation, delivery, and lactation remove females from groups for prolonged intervals. As the macaque cervix does not facilitate transcervical surgical termination of pregnancy, we sought to establish a medical termination protocol.
Methods: A descriptive case series of outcomes of medical termination of pregnancy up to 32 days gestation in cynomolgus monkeys. Efficacy and time to uterine resolution were determined according to medication, dose, and route of administration.
Results: Thirty-seven macaques underwent 65 medical terminations. Over 80% of animals terminated after initial treatment with mifepristone 20 mg intramuscularly (IM). Intrafetal methotrexate was effective for salvage treatment. Medical termination regimens were less effective for animals receiving investigational contraceptive agents.
Conclusions: Medical termination for macaques is safe and effective. We recommend a protocol with mifepristone 20 mg IM and misoprostol 200 µg buccally as initial treatment.
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http://dx.doi.org/10.1111/jmp.12019 | DOI Listing |
Background: The autophagy lysosomal pathway (ALP) and the ubiquitin-proteasome system (UPS) are key proteostasis mechanisms in cells, which are dysfunctional in AD and linked to protein aggregation and neuronal death. Autophagy is over activated in Alzheimer's disease brain whereas UPS is severely impaired. Activating autophagy has received most attention, however recent evidence suggests that UPS can clear aggregate proteins and a potential therapeutic target for AD and protein misfolding diseases.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Keck School of Medicine at University of Southern California, Los Angeles, CA, USA.
Background: ABCA1-mediated cholesterol transport is a central feature in many lipid- dependent diseases including APOE4-associated Alzheimer's disease and atherosclerosis-CVD. ABCA1 upregulation of RNA transcription by nuclear factors (LXR, RXR) have been associated with liver side-effects because of the common promotor element for ABCA1 and Fatty Acid Synthase. The ABCA1 agonist CS6253, derived from the C-terminal of apoE was designed to stabilize and enhance ABCA1 function, thereby providing a safe alternative to transcriptional upregulation.
View Article and Find Full Text PDFRationale: Prior work has shown a preference among most people with dementia and their families for comfort-focused care near the end-of-life. Nonetheless, intubation and mechanical ventilation are increasing over time without concurrent trends in improved survival, including among those with advanced dementia. A better understanding of prehospital decision-making about intubation for people with dementia will guide efforts to increase goal-concordant care at onset of critical illness.
View Article and Find Full Text PDFAnaesth Rep
January 2025
Department of Anaesthesia Rabin Medical Centre, Beilinson Hospital Petah Tikva Israel.
Venous thromboembolic disease remains a leading cause of maternal morbidity and mortality. We report a case of a 30-year-old woman at 37 gestation with a history of thalassaemia intermedia and splenectomy. During pregnancy, she had been managed with frequent blood transfusions and enoxaparin.
View Article and Find Full Text PDFSmall
January 2025
Leicester Institute for Pharmaceutical Innovation, Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester, LE1 9BH, UK.
Guiding molecular assembly of peptides into rationally engineered nanostructures remains a major hurdle against the development of functional peptide-based nanomaterials. Various non-covalent interactions come into play to drive the formation and stabilization of these assemblies, of which electrostatic interactions are key. Here, the atomistic mechanisms by which electrostatic interactions contribute toward controlling self-assembly and lateral association of ultrashort β-sheet forming peptides are deciphered.
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