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Proliferative stem cells maintain quiescence of their niche by secreting the Activin inhibitor Follistatin

Herrera, Salvador C; Sainz de la Maza, Diego; Grmai, Lydia; Margolis, Shally; Plessel, Rebecca; Burel, Michael; O'Connor, Michael; Amoyel, Marc; Bach, Erika A
Aging causes stem cell dysfunction as a result of extrinsic and intrinsic changes. Decreased function of the stem cell niche is an important contributor to this dysfunction. We use the Drosophila testis to investigate what factors maintain niche cells. The testis niche comprises quiescent "hub" cells and supports two mitotic stem cell pools: germline stem cells and somatic cyst stem cells (CySCs). We identify the cell-cycle-responsive Dp/E2f1 transcription factor as a crucial non-autonomous regulator required in CySCs to maintain hub cell quiescence. Dp/E2f1 inhibits local Activin ligands through production of the Activin antagonist Follistatin (Fs). Inactivation of Dp/E2f1 or Fs in CySCs or promoting Activin receptor signaling in hub cells causes transdifferentiation of hub cells into fully functional CySCs. This Activin-dependent communication between CySCs and hub regulates the physiological decay of the niche with age and demonstrates that hub cell quiescence results from signals from surrounding stem cells.
PMCID:8387025
PMID: 34363758
ISSN: 1878-1551
CID: 5004332

COVID-19, Personal Protective Equipment, and Human Performance

Ruskin, Keith J; Ruskin, Anna Clebone; Musselman, Brian T; Harvey, Jaime Rivas; Nesthus, Thomas E; O'Connor, Michael
Clinicians who care for patients infected with coronavirus disease 2019 (COVID-19) must wear a full suite of personal protective equipment, including an N95 mask or powered air purifying respirator, eye protection, a fluid-impermeable gown, and gloves. This combination of personal protective equipment may cause increased work of breathing, reduced field of vision, muffled speech, difficulty hearing, and heat stress. These effects are not caused by individual weakness; they are normal and expected reactions that any person will have when exposed to an unusual environment. The physiologic and psychologic challenges imposed by personal protective equipment may have multiple causes, but immediate countermeasures and long-term mitigation strategies can help to improve a clinician's ability to provide care. Ultimately, a systematic approach to the design and integration of personal protective equipment is needed to improve the safety of patients and clinicians.
PMID: 33404638
ISSN: 1528-1175
CID: 4738952

Chest Compression Duration May Be Improved When Rescuers Breathe Supplemental Oxygen

Clebone, Anna; Reis, Katherine; Tung, Avery; OConnor, Michael; Ruskin, Keith J
BACKGROUND: At sea level, performing chest compressions is a demanding physical exercise. On a commercial flight at cruise altitude, the barometric pressure in the cabin is approximately equal to an altitude of 2438 m. This results in a Poâ‚‚ equivalent to breathing an FIoâ‚‚ of 15% at sea level, a condition under which both the duration and quality of cardiopulmonary resuscitation (CPR) may deteriorate. We hypothesized that rescuers will be able to perform fewer rounds of high-quality CPR at an FIoâ‚‚ of 15%.METHODS: In this crossover simulation trial, 16 healthy volunteers participated in 2 separate sessions and performed up to 14 2-min rounds of chest compressions at an FIoâ‚‚ of either 0.15 or 0.21 in randomized order. Subjects were stopped if their Spoâ‚‚ was below 80%, if chest compression rate or depth was not achieved for 2/3 of compressions, or if they felt fatigued or dyspneic.RESULTS: Fewer rounds of chest compressions were successfully completed in the hypoxic than in the normoxic condition, (median [IQR] 4.5 [3,8.5]) vs. 5 [4,14]). The decline in arterial Spoâ‚‚ while performing chest compressions was greater in the hypoxic condition than in the normoxic condition [mean (SD), 6.19% (4.1) vs. 2% (1.66)].DISCUSSION: Our findings suggest that the ability of rescuers to perform chest compressions in a commercial airline cabin at cruising altitude may be limited due to hypoxia. One possible solution is supplemental oxygen for rescuers who perform chest compressions for in-flight cardiac arrest.Clebone A, Reis K, Tung A, OConnor M, Ruskin KJ. Chest compression duration may be improved when rescuers breathe supplemental oxygen. Aerosp Med Hum Perform. 2020; 91(12):918922.
PMID: 33243334
ISSN: 2375-6322
CID: 4680992

Automation failures and patient safety

Ruskin, Keith J; Ruskin, Anna Clebone; O'Connor, Michael
PURPOSE OF REVIEW/OBJECTIVE:The goal of automation is to decrease the anesthesiologist's workload and to decrease the possibility of human error. Automated systems introduce problems of its own, however, including loss of situation awareness, leaving the physician out of the loop, and training physicians how to monitor autonomous systems. This review will discuss the growing role of automated systems in healthcare and describe two types of automation failures. RECENT FINDINGS/RESULTS:An automation surprise occurs when an automated system takes an action that is unexpected by the user. Mode confusion occurs when the operator does not understand what an automated system is programmed to do and may prevent the clinician from fully understanding what the device is doing during a critical event. Both types of automation failures can decrease a clinician's trust in the system. They may also prevent a clinician from regaining control of a failed system (e.g., a ventilator that is no longer working) during a critical event. SUMMARY/CONCLUSIONS:Clinicians should receive generalized training on how to manage automation and should also be required to demonstrate competency before using medical equipment that employs automation, including electronic health records, infusion pumps, and ventilators.
PMID: 33093302
ISSN: 1473-6500
CID: 4642532

Defining oral neglect in institutionalized elderly: a consensus definition for the protection of vulnerable elderly people

Katz, Ralph V; Smith, Barbara J; Berkey, Douglas B; Guset, Adela; O'Connor, Michael P
BACKGROUND: The authors administered surveys to develop an operational definition of oral neglect in institutionalized elderly (ONiIE) in the United States. METHODS: The authors administered a Delphi technique survey involving three rounds to a panel of 19 geriatric dental experts in 1995 to arrive at a definition of ONiIE. The authors validated the 1995 ONiIE definition by administering a Delphi technique survey involving four rounds to a subset of eight experts from the 1995 panel. RESULTS: The panelists in the 2009 survey validated the 28 oral diseases or conditions that were part of the 1995 ONiIE definition and added one new oral condition-bleeding. They also reached consensus agreement for each of the 29 listed oral diseases and conditions regarding both the diagnostic stage at which those diseases and conditions should be included in a definition (mild, moderate, or severe) and the specified time period required to constitute neglect (that is, total 'time to qualify as neglect' was eight days for acute conditions and 35 days for chronic conditions). CONCLUSIONS: An expert-driven consensus ONiIE definition was established. It consists of 29 oral diseases and conditions, each of which has been associated with a diagnostic stage and a specified time period required to constitute neglect. CLINICAL IMPLICATIONS: Since federal legislation that funds payments to nursing homes for the care and housing of their residents requires that there shall be no oral neglect, this validated consensus ONiIE definition provides a utilitarian means to enforce that legislative expectation
PMID: 20354093
ISSN: 1943-4723
CID: 155107