Secretory pathway calcium ATPase 1 (SPCA1) controls mouse neural tube closure by regulating cytoskeletal dynamics.

Neural tube closure relies on the apical constriction of neuroepithelial cells. Research in frog and fly embryos has found links between the levels of intracellular calcium, actomyosin dynamics and apical constriction. However, genetic evidence for a role of calcium in apical constriction during mammalian neurulation is still lacking. Secretory pathway calcium ATPase (SPCA1) regulates calcium homeostasis by pumping cytosolic calcium into the Golgi apparatus. Loss of function in Spca1 causes cranial exencephaly and spinal cord defects in mice, phenotypes previously ascribed to apoptosis. However, our characterization of a novel allele of Spca1 revealed that neurulation defects in Spca1 mutants are not due to cell death, but rather to a failure of neuroepithelial cells to apically constrict. We show that SPCA1 influences cell contractility by regulating myosin II localization. Furthermore, we found that loss of Spca1 disrupts actin dynamics and the localization of the actin remodeling protein cofilin 1. Taken together, our results provide evidence that SPCA1 promotes neurulation by regulating the cytoskeletal dynamics that promote apical constriction and identify cofilin 1 as a downstream effector of SPCA1 function.

Pbx loss in cranial neural crest, unlike in epithelium, results in cleft palate only and a broader midface.

Orofacial clefting represents the most common craniofacial birth defect. Cleft lip with or without cleft palate (CL/P) is genetically distinct from cleft palate only (CPO). Numerous transcription factors (TFs) regulate normal development of the midface, comprising the premaxilla, maxilla and palatine bones, through control of basic cellular behaviors. Within the Pbx family of genes encoding Three Amino-acid Loop Extension (TALE) homeodomain-containing TFs, we previously established that in the mouse, Pbx1 plays a preeminent role in midfacial morphogenesis, and Pbx2 and Pbx3 execute collaborative functions in domains of coexpression. We also reported that Pbx1 loss from cephalic epithelial domains, on a Pbx2- or Pbx3-deficient background, results in CL/P via disruption of a regulatory network that controls apoptosis at the seam of frontonasal and maxillary process fusion. Conversely, Pbx1 loss in cranial neural crest cell (CNCC)-derived mesenchyme on a Pbx2-deficient background results in CPO, a phenotype not yet characterized. In this study, we provide in-depth analysis of PBX1 and PBX2 protein localization from early stages of midfacial morphogenesis throughout development of the secondary palate. We further establish CNCC-specific roles of PBX TFs and describe the developmental abnormalities resulting from their loss in the murine embryonic secondary palate. Additionally, we compare and contrast the phenotypes arising from PBX1 loss in CNCC with those caused by its loss in the epithelium and show that CNCC-specific Pbx1 deletion affects only later secondary palate morphogenesis. Moreover, CNCC mutants exhibit perturbed rostro-caudal organization and broadening of the midfacial complex. Proliferation defects are pronounced in CNCC mutants at gestational day (E)12.5, suggesting altered proliferation of mutant palatal progenitor cells, consistent with roles of PBX factors in maintaining progenitor cell state. Although the craniofacial skeletal abnormalities in CNCC mutants do not result from overt patterning defects, osteogenesis is delayed, underscoring a critical role of PBX factors in CNCC morphogenesis and differentiation. Overall, the characterization of tissue-specific Pbx loss-of-function mouse models with orofacial clefting establishes these strains as unique tools to further dissect the complexities of this congenital craniofacial malformation. This study closely links PBX TALE homeodomain proteins to the variation in maxillary shape and size that occurs in pathological settings and during evolution of midfacial morphology.

Twice-Daily Huddles Improves Collaborative Problem Solving in the Respiratory Care Department.

BACKGROUND: Lean Six Sigma processes are used in health care systems to increase safety and efficiency. Daily huddles, one tool of the Lean Six Sigma process, have been used to increase patient safety, facilitate efficiency in problem solving, promote optimal patient outcomes, and reduce poor communication. Huddle utilization by respiratory care departments has not been previously reported. We describe our process of implementing daily huddles and the impact on departmental problem solving. METHOD: A descriptive study of a quality improvement intervention and a retrospective study of prospectively collected data were performed. The respiratory care department was trained in the utilization of a daily huddle process to resolve issues and identify process improvement opportunities. Huddles were performed at the beginning of each shift. Process improvement opportunities were raised by the respiratory therapy staff using the following categories: Safety/Service, Methods, Equipment, Supplies, and Associates. Opportunities were placed within 3 categories; quick hits (resolution in 1-3 d), complex problems (resolution in 3-7 d), and projects (resolution in > 7 d). All opportunities included a problem statement, an immediate countermeasure, a problem leader, and a due date. Items requiring interdisciplinary support were escalated to the organizational patient care services huddle. We evaluated the number and nature of process improvement opportunities raised in huddles from January 1 through December 31, 2018, to better understand the impact of daily huddles. RESULTS: A total of 366 process improvement opportunities were raised during huddles. Of those, 245 (67%) were quick hits, 77 (21%) were complex, and 44 (12%) were projects. Resolution of 174 (47.5%) opportunities was completed using only the resources of the respiratory care department, and 157 (43%) were resolved with additional interdisciplinary involvement. A small portion 35 (9.5%) of opportunities required escalation to the organizational multidisciplinary huddle for resolution. All process improvement opportunities were resolved at the end of the study period (mean ± SD of 30.5 ± 7.7 per month). CONCLUSIONS: Twice-daily huddles implemented by our respiratory care department allowed for identification and timely resolution of process improvement opportunities.

Occupational-Induced Secondary Traumatic Stress and Posttraumatic Stress Disorder in Respiratory Therapists.

BACKGROUND: Secondary traumatic stress (STS) may occur in the caretakers of individuals who have experienced traumatic events or are suffering and, when severe, may be associated with posttraumatic stress disorder (PTSD) at a diagnostic level due to STS. For respiratory therapists (RTs), the incidence of STS and PTSD at a diagnostic level due to STS has not been examined. We assessed the prevalence of self-reported STS and PTSD at a diagnostic level due to STS in licensed RTs. METHODS: Licensed RTs who were members of the American Association for Respiratory Care completed the Secondary Traumatic Stress Scale (STSS) based on feelings experienced over the preceding 30 days and 12 months. Results were evaluated on the basis of primary patient population (neonatal/pediatric vs adult), years of experience, and usual work location (ambulatory care, acute care, or ICU) using the McNemar chi-square analysis and the Fisher exact test. RESULTS: 201 licensed and practicing RTs completed the survey. 92% of the respondents worked ≥ 30 h/week, 75% worked in ICUs, 67% worked primarily with adults, and 89% had been in practice ≥ 6 years. PTSD at a diagnostic level due to STS was common in all respondents, occurring in 36% based on experiences from the prior 30 days and in 32% based on experiences from the prior 12 months. CONCLUSIONS: No difference in PTSD at a diagnostic level due to STS was noted between RTs caring for neonatal/pediatric versus adult patients or between RTs based on years of work experience or based on work environment. STS and PTSD at a diagnostic level due to STS was common in RTs.

Impact of Helium-Oxygen Administered via High Velocity Nasal Insufflation on Delivery of Inhaled Nitric Oxide.

Inhaled nitric oxide (iNO) may be continued during the transition from invasive to noninvasive respiratory support. Upper airway obstruction from laryngeal edema following extubation and lower airway obstruction from asthma and bronchiolitis may be managed with inhaled helium. The coadministration of helium with iNO and the impact on delivered amounts of iNO have not been extensively studied. A bench model simulating a spontaneously breathing infant received iNO at varying preset doses delivered with either helium-oxygen or nitrogen-oxygen via a Vapotherm unit. iNO levels were measured at the simulated trachea. Results from the two conditions were compared using t-tests. When nitrogen-oxygen was used, there was no difference between preset and measured iNO levels. A significant difference was present when helium-oxygen was used, with a 10-fold increase in measured iNO levels compared with preset values. The use of helium resulted in a significant increase in measured iNO at the level of the simulated trachea. Clinicians must be aware that iNO will not be delivered at prescribed doses when used with helium under the conditions used in this study.