Summary
Hematopoietic stem cells (HSCs) reside in hypoxic niches within bone marrow and cord blood. Yet, essentially all HSC studies have been performed with cells isolated and processed in non-physiologic ambient air. By collecting and manipulating bone marrow and cord blood in native conditions of hypoxia, we demonstrate that brief exposure to ambient oxygen decreases recovery of long-term repopulating HSCs and increases progenitor cells, a phenomenon we term Extra Physiologic Oxygen Shock/Stress (EPHOSS). Thus, true numbers of HSCs in the bone marrow and cord blood are routinely underestimated. We linked ROS production and induction of the mitochondrial permeability transition pore (MPTP) via cyclophilin D and p53 as mechanisms of EPHOSS. MPTP inhibitor Cyclosporine A protects mouse bone marrow and human cord blood HSCs from EPHOSS during collection in air, resulting in increased recovery of transplantable HSCs. Mitigating EPHOSS during cell collection and processing by pharmacological means may be clinically advantageous for transplantation.
Objective
The objective of this prospective cohort study was to determine if sleep disordered breathing during pregnancy is a risk factor for the development of hypertensive disorders of pregnancy and gestational diabetes mellitus.
Methods
Nulliparous women underwent in-home sleep disordered breathing assessments in early (6–15 weeks) and mid-pregnancy (22–31 weeks). Participants and providers were blinded to the sleep test results. An apnea-hypopnea index (AHI) of ≥5 was used to define sleep disordered breathing. Exposure-response relationships were examined grouping participants into four AHI groups: AHI=0, 0
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