Does Mandibular Distraction Osteogenesis for Robin Sequence Create Altered Craniofacial Morphology and Disrupt Tooth Development?

BACKGROUND: Robin Sequence (RS) infant patients may require mandibular distraction osteogenesis (MDO) to improve airway. The distracted mandible may grow vertically and the developing dentition may be disrupted. PURPOSE: The study purpose was to measure the association of MDO on craniofacial morphology and tooth development in RS subjects. STUDY DESIGN, SETTING, SAMPLE: This was a retrospective cohort study of RS infants treated with or without MDO. Inclusion criteria were RS diagnosis, complete imaging, and treatment at our pediatric regional hospital. Exclusion criteria were treatment elsewhere and insufficient imaging. EXPOSURE VARIABLE: Exposure was airway management; subjects were grouped by use of MDO or not. Subjects were compared to age-matched normal infants presurgically and to age-matched normal controls at follow-up. MAIN OUTCOME VARIABLES: Main outcome variables were craniofacial morphology measured using cephalometric gonial angle and ramus height to mandibular body length ratio presurgically (T1), postsurgically (T2), and at the mixed dentition (T3). Disrupted tooth development was assessed by absence/abnormality of teeth on radiographs at T3. COVARIATES: Covariates were age, sex, body mass index, comorbidities, and cephalometric measurements. ANALYSES: Appropriate univariate, bivariate, and regression models were computed, and significance level was set at P < .05. RESULTS: The sample contained 14 RS-MDO subjects with median age of 1.1 months and 10 (71.4%) were female. Presurgery, RS-MDO subjects had significantly more obtuse gonial angles (145° vs 137°, P = .04) and shorter mandibular bodies (32 vs 41 mm, P < .01) than the 37 unaffected controls. Increased ramus height (P < .01) and mandibular body length (P < .01) and forward rotation of the mandible were seen in 12 subjects with post-MDO imaging compared to their presurgical condition. At mixed dentition, 12 post-MDO subjects had more obtuse gonial angles (P < .01) and steeper mandibular planes (P < .01) than 19 non-MDO RS subjects. Both RS groups had different cephalometric values and more vertical measures than matched cephalometric norms. Thirty-one percent of 12 RS-MDO subjects had ≥1 teeth with abnormal development compared to none of 19 RS subjects without MDO (P = .02). CONCLUSION AND RELEVANCE: MDO increased mandibular size in infants but can disrupt the developing dentition. Postdistraction growth may result in more vertical mandibular morphology with large gonial angles.

Isolation, Culture, and Phenotypic Analysis of Murine Lung Organoids.

Three-dimensional (3D) organoid cultures retain self-renewing stem cells that differentiate into multiple cell types that display spatial organization and functional key features, providing a highly physiological relevant system. Here we describe a strategy for the generation of 3D murine lung organoids derived from freshly isolated primary tracheal and distal lung epithelial stem cells. Isolated tracheas are subjected to enzymatic digestion to release the epithelial layer that is then dissociated into a single cell suspension for organoid culture. Lung epithelial cells are obtained from dissected lobes, which are applied to mechanical and enzymatic dissociation. After flow sorting, organoids are established from tracheal basal, secretory club, and alveolar type 2 cells in the defined conditioned medium that is required to sustain organoid growth and generate the differentiated cells. Multi-cell-type organoid co-culture replicates niches for distal epithelial stem cells to differentiate into bronchiolar and alveolar cell types. Established organoids can be fixed for wholemount staining and paraffin embedding, or passaged for further culture. Taken together, this protocol provides an efficient and validated approach to generate murine lung organoids, as well as a platform for further analysis.

Improving Craniofacial Team Collaboration: A Multicenter Interview Study of Effective Team Meetings.

Objective: In the USA, the American Cleft Palate Association-Craniofacial Association (ACPA-CPF) specifies guidelines to ensure craniofacial teams function in a multidisciplinary fashion to provide care in a sequence that mirrors the patient's needs. Among these guidelines is the expectation that teams hold regular multidisciplinary team meetings to discuss patient care. The purpose of this study was to identify factors that contribute to optimal team functioning during these meetings. The impact of the virtual format on meetings was also evaluated. Design: One-hour semi-structured interviews of craniofacial team members, queried on current and ideal team meetings, were conducted from December 2020 - January 2021. Interviews were recorded, transcribed, and coded to identify common themes until thematic saturation was achieved. Setting/Participants: Sixteen team members from three major American craniofacial centers were interviewed virtually. Results: Three major categories were identified as integral to successful meetings: (1) meeting content, (2) meeting processes, and (3) team dynamics. Within these categories are several factors that participants reported as important to optimize their multidisciplinary meetings: key content for discussions, integration of patient perspective, recognition of collaboration in determining proper sequence of treatments, an attentive discussion leader promoting equitable discussions, managing absences, and team diversity. Participants also identified benefits and pitfalls of hosting meetings in the virtual setting, including lack of engagement and awkward communication. Conclusion: Diverse groups of disciplines are expected to come together during craniofacial multidisciplinary meetings to formulate intricate care plans for complex patients. In this study, craniofacial team members have identified several key factors to optimize these meetings. The research group used these factors to propose a self-evaluation instrument for meeting quality improvement, provided in printable format. Further studies should evaluate how implementation of these factors affects meetings and ultimately guides patient care.

Growth Patterns Between Ages 0 and 36 Months Among US Children With Orofacial Cleft: A Retrospective Cohort Study.

BACKGROUND: Little is known about how young children with orofacial cleft grow over time. OBJECTIVE: To characterize longitudinal growth patterns from ages 0 to 36 months in US children with an orofacial cleft. DESIGN: A retrospective cohort study. PARTICIPANTS/SETTING: Children with cleft lip, cleft lip and palate, or cleft palate who were younger than age 36 months at a hospital encounter between 2010 and 2019 (N = 1334) were included. The setting was a US tertiary care children's hospital with a cleft center that serves a 5-state region. MAIN OUTCOME MEASURE: Weight-for-age z scores (WAZ) and length-for-age z scores (LAZ). STATISTICAL ANALYSES PERFORMED: Longitudinal growth patterns were characterized using generalized linear mixed models to estimate mean WAZ and LAZ from age 0 to 36 months. RESULTS: Growth in infants with cleft slowed dramatically during the first 3 to 4 months of life, rebounded with catch-up growth until age 12 months for cleft lip and cleft palate and until age 36 months for cleft lip and palate. When comparing populations, children with any type of cleft demonstrated subpar growth compared with World Health Organization standards. Growth deficits were more common in those with cleft lip and palate and cleft palate compared with those with cleft lip. The intraclass coefficient showed that most of the variability in the WAZ (65%) was between individuals, whereas 35% was within an individual. The intraclass coefficient for LAZ showed that most of the variability in the LAZ (74%) was between individuals, whereas 26% was within an individual. The proportion of variance attributable to cleft type and/or comorbidities accounted for <5% of the variance for WAZ and LAZ. WAZ and LAZ were lower in children with comorbidities than those without comorbidities with cleft and World Health Organization standards. CONCLUSIONS: Infants with cleft lip and palate, cleft palate, and a cleft with comorbidities have higher rates of poor growth than peers with cleft lip and a cleft with no comorbidities, respectively.

Expression of the Arabidopsis redox-related LEA protein, SAG21 is regulated by ERF, NAC and WRKY transcription factors.

SAG21/LEA5 is an unusual late embryogenesis abundant protein in Arabidopsis thaliana, that is primarily mitochondrially located and may be important in regulating translation in both chloroplasts and mitochondria. SAG21 expression is regulated by a plethora of abiotic and biotic stresses and plant growth regulators indicating a complex regulatory network. To identify key transcription factors regulating SAG21 expression, yeast-1-hybrid screens were used to identify transcription factors that bind the 1685 bp upstream of the SAG21 translational start site. Thirty-three transcription factors from nine different families bound to the SAG21 promoter, including members of the ERF, WRKY and NAC families. Key binding sites for both NAC and WRKY transcription factors were tested through site directed mutagenesis indicating the presence of cryptic binding sites for both these transcription factor families. Co-expression in protoplasts confirmed the activation of SAG21 by WRKY63/ABO3, and SAG21 upregulation elicited by oligogalacturonide elicitors was partially dependent on WRKY63, indicating its role in SAG21 pathogen responses. SAG21 upregulation by ethylene was abolished in the erf1 mutant, while wound-induced SAG21 expression was abolished in anac71 mutants, indicating SAG21 expression can be regulated by several distinct transcription factors depending on the stress condition.

Psychological dread and extreme persistent fear.

Psychological dread is a phenomenon with which virtually everyone is familiar, whether dreading a medical appointment, a job interview, or the impending death of a loved one. Despite the prevalence of dread in most people's everyday lives, surprisingly little empirical research has explored the construct. The purpose of the current research was to examine psychological dread (Study 1 and Study 2) and to compare dread to extreme persistent fear (Study 2). Respondents across both studies completed surveys on which they described a dreaded experience (Studies 1 and 2) or an extremely feared event (Study 2) and answered questions about the event. Participants reported uncertainty and lack of control surrounding events associated with both dread and extreme persistent fear. They also anticipated that they would feel relief when these events were over, but this relief was greater with dread than fear. Implications for coping with dread and extreme persistent fears are discussed along with comparisons of the types of events most commonly associated with dread and extreme fear.

Difficult intubation in syndromic versus nonsyndromic forms of micrognathia in children.

BACKGROUND: We investigated how syndromic versus nonsyndromic forms of micrognathia impacted difficult intubation outcomes in children. Primary outcome was the first-attempt success rate of tracheal intubation, secondary outcomes were number of intubation attempts and complications. We hypothesized that syndromic micrognathia would be associated with lower first-attempt success rate. METHODS: In micrognathic patients enrolled in the Pediatric Difficult Intubation Registry (08/2012-03/2019) we retrospectively compared demographic and clinical characteristics between children with nonsyndromic and syndromic micrognathia using standardized mean differences (SMD) and assessed the association of the presence of syndrome with the primary and secondary outcomes using propensity score matching analysis with and without matching for airway assessment findings. RESULTS: Nonsyndromic patients (628) were less likely to have additional airway abnormalities. Syndromic patients (216) were less likely to have unanticipated difficult intubation (2% vs. 20%, SMD 0.59). First-attempt success rates of intubation were: 38% in the syndromic versus 34% in the nonsyndromic group (odds ratio [OR] 1.18; 95% confidence intervals [95% CI] 0.74, 1.89; p = .478), and 37% versus 37% (OR 0.99; 95% CI 0.66, 1.48; p = .959). Median number of intubation attempts were 2 (interquartile range [IQR]: 1, 3; range: 1, 8) versus 2 (IQR: 1, 3; range 1, 12) (median regression coefficient = 0; 95% CI: -0.7, 0.7; p = .999) and 2 (IQR: 1, 3; range: 1, 12) versus 2 (IQR: 1, 3; range 1, 8) (median regression coefficient = 0; 95% CI: -0.5, 0.5; p = .999). Complication rates were 14% versus 22% (OR 0.6; 95% CI 0.34, 1.04; p = .07) and 16% versus 21% (OR 0.71; 95% CI 0.43, 1.17; p = .185). CONCLUSIONS: Presence of syndrome was not associated with lower first-attempt success rate on intubation, number of intubation attempts, or complication rate among micrognathic patients difficult to intubate, despite more associated craniofacial abnormalities. Nonsyndromic patients were more likely to have unanticipated difficult intubations, first attempt with direct laryngoscopy.

Child Sexual Abuse Documentation in Primary Care Settings.

Primary care providers (PCPs) can play an important role in the continuity of care for children who experience sexual abuse (SA). We performed a retrospective, chart-based study of children 3 to 17 years old with SA history. Primary care medical records were reviewed for 2 years after a subspecialty SA evaluation. Descriptive statistics and logistic regression were used to assess factors associated with documentation of SA history and mental health management by the PCP. Of 131 included patients, 43% had PCP documentation of their SA history, which was associated with care from resident providers (P < .01). There was greater mental health management and mental health referrals by PCPs for the group with documentation compared with the group without documentation (52% vs 23%, P < .001). Overall, child SA history was poorly documented in primary care settings. Identifying mechanisms to improve communication about a child's SA history with PCPs is important for the child's ongoing care.

What Do Child Abuse and Neglect Medical Evaluation Consultation Notes Tell Researchers and Clinicians?

Child abuse and neglect (CAN) medical experts provide specialized multidisciplinary care to children when there is concern for maltreatment. Their clinical notes contain valuable information on child- and family-level factors, clinical concerns, and service placements that may inform the needed supports for the family. We created and implemented a coding system for data abstraction from these notes. Participants were 1,397 children ages 0-17 years referred for a consultation with a CAN medical provider at an urban teaching and research hospital between March 2013 and December 2017. Coding themes were developed using an interdisciplinary team-based approach to qualitative analysis, and descriptive results are presented using a developmental-contextual framework. This study demonstrates the potential value of developing a coding system to assess characteristics and patterns from CAN medical provider notes, which could be helpful in improving quality of care and prevention and detection of child abuse.

Feasibility and Acceptability of the Promoting Resilience in Stress Management-Parent (PRISM-P) Intervention for Caregivers of Children with Craniofacial Conditions.

OBJECTIVES: Few evidence-based psychosocial programs exist within craniofacial care. This study (a) assessed feasibility and acceptability of the Promoting Resilience in Stress Management-Parent (PRISM-P) intervention among caregivers of children with craniofacial conditions and (b) described barriers and facilitators of caregiver resilience to inform program adaptation. DESIGN: In this single-arm cohort study, participants completed a baseline demographic questionnaire, the PRISM-P program, and an exit interview. PARTICIPANTS: Eligible individuals were English-speaking legal guardians of a child <12-years-old with a craniofacial condition. INTERVENTION: PRISM-P included 4 modules (stress-management, goal-setting, cognitive-restructuring, meaning-making) delivered in 2 one-on-one phone or videoconference sessions 1-2 weeks apart. MAIN OUTCOME MEASURES: Feasibility was defined as >70% program completion among enrolled participants; acceptability was defined as >70% willingness to recommend PRISM-P. Intervention feedback and caregiver-perceived barriers and facilitators of resilience were summarized qualitatively. RESULTS: Twenty caregivers were approached and 12 (60%) enrolled. The majority were mothers (67%) of a child <1-year-old diagnosed with a cleft lip and/or palate (83%) or craniofacial microsomia (17%). Of these, 8 (67%) completed PRISM-P and 7 (58%) completed interviews; 4 (33%) were lost-to-follow-up before PRISM-P and 1 (8%) before the interview. Feedback was highly positive, with 100% willing to recommend PRISM-P. Perceived barriers to resilience included uncertainty about their child's health; facilitators included social support, parental identity, knowledge, and control. CONCLUSIONS: PRISM-P was acceptable among caregivers of children with craniofacial conditions but not feasible based on program completion rates. Barriers and facilitators of resilience support the appropriateness of PRISM-P for this population and inform adaptation.

A Cross-Sectional Study of the Nutritional Status of Infants with Orofacial Clefts in the First 6 Months of Life.

OBJECTIVE(S): To estimate nutritional status in a large cohort of infants with orofacial clefts in the US, overall and by cleft type from birth to 6 months of age. STUDY DESIGN: We conducted a cross-sectional study in infants with orofacial clefts by examining growth by month between birth and 6 months of age. Infants with at least one weight measurement at a single US regional tertiary care pediatric hospital with an interdisciplinary cleft team between 2010 and 2020 were included. We calculated the average weight-for-age z scores and weight-for-length z scores. We calculated the proportion of infants underweight and wasting with z scores below -2 SDs monthly from birth to 6 months of age. We used t tests to compare the distribution of weight for age z-score and weight for length z-score among children with orofacial clefts to a normal distribution. RESULTS: We included 883 infants with orofacial clefts. Compared with expected proportion of underweight infants (2.3%), a larger proportion of infants with orofacial clefts were underweight between birth and 1 month (10.6%), peaking between 2 and 3 months (27.1%), and remaining high between 5 and 6 months (16.3%). Compared with the expected proportion of infants with wasting (2.3%), a higher proportion of infants with orofacial clefts experienced wasting between birth and 1 month (7.3%), peaking between 2 and 3 months (12.8%), and remaining high between 5 and 6 months (5.3%). Similar findings were observed for all cleft types and regardless of comorbidities. CONCLUSION(S): A substantial proportion of infants with orofacial clefts compared with normative peers have malnutrition in the first 6 months of life in the US.

Protection Motivation Theory and Intentions to Receive the COVID-19 Vaccine.

Background. Declared a "public health threat of international concern" by the World Health Organization, the COVID-19 virus has caused the deaths of over half a million individuals in the United States in just the first 23 months after detection. The vaccine has recently been introduced to reduce this public health threat. However, due, in part, to the rapidity with which the vaccine was developed, many individuals display vaccine hesitancy. Purpose. The current study examined the utility of the Protection Motivation Theory of Health (PMT) in predicting intentions to receive the COVID-19 vaccine. Method. One hundred twenty-nine unvaccinated respondents (drawn from an initial sample of 255 participants) completed a survey assessing the components of the PMT and intentions to receive the vaccine. Respondents could also provide an open-ended response regarding any concerns they had with the vaccine. Conclusions. The PMT accounted for 76% of the variance in vaccine intentions. Vulnerability, outcome efficaciousness, and maladaptive response rewards each accounted for unique variance. Open-ended responses reflecting concerns with the vaccine fell into 8 categories, with the most common being concern with the long-term side effects of the vaccine. These results suggest that public health campaigns promoting the vaccine should focus on vulnerability to COVID-19, protective functions of the vaccine, and overcoming what people perceive as benefits of not receiving the vaccine.

What do child maltreatment reports to Child Protective Services tell us about the needs families and communities are experiencing?

Intake reports from child protective service (CPS) agencies are the foundation for subsequent decisions and services within the child welfare system. They provide valuable information for understanding children's needs, yet the unstructured way that information is captured makes the information ascertained in these reports difficult to summarize. Utilizing CPS intake reports from a mid-sized urban county in the southeastern United States (N = 2,724), our study had three aims: (1) develop a coding system to abstract information from narrative CPS intake reports, (2) examine the prevalence of maltreatment subtypes, and (3) compare prevalence of maltreatment subtypes by screen-in/screen-out decisions. Improper discipline/physical abuse was the most common maltreatment subtype (34.6 %); over 40 % of reports involved a physical act toward the child not resulting in injury. Salient risk factors included caregiver drug use (20.6 %) and domestic violence (19 %). While substantial discrepancies were not found between screened-in and screened-out cases with respect to maltreatment types, maltreatment type-specific codes, or contributory factors, they were found for reporter type and child age. Our coding system to extract and assess child maltreatment intake narrative data can provide local agencies with descriptive information about why children come to their agency's attention and provide nuanced details regarding the children's and families' needs. This coding framework could be used to develop validated intake tools to better document and categorize child maltreatment which could inform the assessment/investigation process and create targeted prevention and intervention services for families that come to the attention of CPS.

Do children evaluated for maltreatment have higher subsequent emergency department and inpatient care utilization compared to a general pediatric sample?

BACKGROUND: Child maltreatment leads to substantial adverse health outcomes, but little is known about acute health care utilization patterns after children are evaluated for a concern of maltreatment at a child abuse and neglect medical evaluation clinic. OBJECTIVE: To quantify the association of having a child maltreatment evaluation with subsequent acute health care utilization among children from birth to age three. PARTICIPANTS AND SETTING: Children who received a maltreatment evaluation (N = 367) at a child abuse and neglect subspecialty clinic in an academic health system in the United States and the general pediatric population (N = 21,231). METHODS: We conducted a retrospective cohort study that compared acute health care utilization over 18 months between the two samples using data from electronic health records. Outcomes were time to first emergency department (ED) visit or inpatient hospitalization, maltreatment-related ED use or inpatient hospitalization, and ED use or inpatient hospitalization for ambulatory care sensitive conditions (ACSCs). Multilevel survival analyses were performed. RESULTS: Children who received a maltreatment evaluation had an increased hazard for a subsequent ED visit or inpatient hospitalization (hazard ratio [HR]: 1.3, 95 % confidence interval [CI]: 1.1, 1.5) and a maltreatment-related visit (HR: 4.4, 95 % CI: 2.3, 8.2) relative to the general pediatric population. A maltreatment evaluation was not associated with a higher hazard of health care use for ACSCs (HR: 1.0, 95 % CI: 0.7, 1.3). CONCLUSION: This work can inform targeted anticipatory guidance to aid high-risk families in preventing future harm or minimizing complications from previous maltreatment.

Protection motivation unmasked: Applying protection motivation theory to skepticism toward COVID-19 mask and vaccine mandates.

Variants of COVID-19 have sparked controversy regarding mask and/or vaccine mandates in some sectors of the country. Many people hold polarized opinions about such mandates, and it is uncertain what predicts attitudes towards these protective behavior mandates. Through a snow-ball sampling procedure of respondents on social media platforms, this study examined skepticism of 774 respondents toward these mandates as a function of the Protection Motivation Theory (PMT) of health. Hierarchical linear regressions examined Protection Motivation (PM) as a predictor of mask and vaccine mandate skepticism independently and with political party affiliation as a control. PM alone accounted for 76% of the variance in mask mandate skepticism, p < 0.001 and 65% in vaccine mandate skepticism, p < 0.001. When political affiliation was entered (accounting for 28% of the variance in mask mandate skepticism, p < 0.001, and 26% in vaccine mandate skepticism, p < 0.001), PM still accounted for significant percentages of variance in both mask (50%) and vaccine (43%) mandate skepticism, ps < 0.001. Across regressions, perceived severity, outcome efficaciousness, and self-efficacy each directly accounted for unique variance in mask and vaccine mandate skepticism, ps < 0.001; only perceived vulnerability failed to account for unique variance in the regressions, ps > 0.05. Specifically, the more severe participants perceived COVID-19 to be and the greater the perceived efficacy of masks and vaccines preventing the spread of COVID-19, the lower participants' skepticism toward mask and vaccine mandates. Similarly, the higher participants' self-efficacy in wearing masks or receiving the vaccine, the lower their skepticism toward mask and vaccine mandates.

Gun violence among young adults with a juvenile crime record in North Carolina: Implications for firearm restrictions based on age and risk.

Youth who acquire a juvenile crime record may be at increased risk of perpetrating gun violence as adults. North Carolina and 22 other states permit young adults who were adjudicated by a juvenile court - even for some felony-equivalent offenses - to legally access firearms. Effectiveness of gun restrictions for adults with juvenile crime histories has not been systematically studied. This article reports findings from a longitudinal study of arrests and convictions for gun-involved and other offenses in 51,059 young adults in North Carolina, comparing those with gun-disqualifying and not-disqualifying juvenile records. The annualized rate of arrest for gun-involved crime in those with a felony-level juvenile record was 9 times higher than the rate of reported comparable offenses in the same age group in the North Carolina general population (3349 vs. 376 per 100,000). Among those with a felony-equivalent juvenile delinquency adjudication who became legally eligible to possess firearms at age 18, 61.8% were later arrested for any criminal offense, 14.3% for a firearm-involved offense. Crimes with guns were most likely to occur among young adults who had committed more serious (felony or equivalent) offenses before age 18; had been adjudicated at younger ages; acquired a felony conviction as a youth; and spent time in prison. The prevalence of arrests for crimes involving guns among young adults in North Carolina with a gun-disqualifying felony record acquired before age 18 suggests that the federal gun prohibitor conferred by a felony record is not highly effective as currently implemented in this population. From a risk-based perspective, these restrictions appear to be justified; better implementation and enforcement may improve their effectiveness. Gun crime prevention policies and interventions should focus on these populations and on limiting illegal access to firearms.

Effects of oral contraceptives on spatial cognition depend on pharmacological properties and phase of the contraceptive cycle.

The central nervous system effects of oral contraceptives (OCs) are not well-documented. In a set of 3 studies, we investigated a specific cognitive function, mental rotation, in healthy women currently using OCs for contraceptive purposes (n = 201) and in medication-free controls not using OCs (n = 44). Mental rotation was measured using a well-standardized and extensively validated psychometric test, the Vandenberg Mental Rotations Test (MRT). In an initial study (Study 1), current OC users (n = 63) were tested during the active or inactive phases of the contraceptive cycle in a parallel-groups design. Studies 2 and 3 were based on an archival dataset (n = 201 current OC users) that consisted of data on the MRT collected in real-time over a 30-year period and compiled for purposes of the present work. The OCs were combined formulations containing ethinyl estradiol (10-35 ug/day) plus a synthetic progestin. All 4 families of synthetic progestins historically used in OCs were represented in the dataset. Cognitive performance was evaluated during either active OC use ('active phase') or during the washout week of the contraceptive cycle ('inactive phase') when OC steroids are not used. The results showed a significant phase-of-cycle (POC) effect. Accuracy on the MRT was mildly diminished during the active phase of OC use, while scores on verbal fluency and speeded motor tasks were modestly improved. The POC effect was most evident in women using OCs that contained first- or second-generation progestins (the estrane family of progestins or OCs containing levonorgestrel), but not in women using OCs containing recently developed progestins and lower doses of ethinyl estradiol. Using independently established ratings of the estrogenic, androgenic, and progestogenic intensities of the different OC formulations, each brand of OC was classified according to its distinct endocrine profile. Multiple regression revealed that the effects of OC use on the MRT could be predicted based on the estrogenic strength of the contraceptives used. Estrogenic potency, not androgenic or anti-androgenic effects of the OC pill, may underlie the effects of OC usage on spatial cognition.

Accuracy and Reliability of 4D-CT and Flexible Laryngoscopy in Upper Airway Evaluation in Robin Sequence.

OBJECTIVES: To evaluate the performance of 4-dimensional computed tomography (4D-CT) in assessing upper airway obstruction (UAO) in patients with Robin sequence (RS) and compare the accuracy and reliability of 4D-CT and flexible fiber-optic laryngoscopy (FFL). STUDY DESIGN: Prospective survey of retrospective clinical data. SETTING: Single, tertiary care pediatric hospital. METHODS: At initial and 30-day time points, a multidisciplinary group of 11 clinicians who treat RS rated UAO severity in 32 sets of 4D-CT visualizations and FFL videos (dynamic modalities) and static CT images. Raters assessed UAO at the velopharynx and oropharynx (1 = none to 5 = complete) and noted confidence levels of each rating. Intraclass correlation and Krippendorff alpha were used to assess intra- and interrater reliability, respectively. Accuracy was assessed by comparing clinician ratings with quantitative percentage constriction (QPC) ratings, calculated based on 4D-CT airway cross-sectional area. Results were compared using Wilcoxon rank-sum and signed-rank tests. RESULTS: There was similar intrarater agreement (moderate to substantial) with 4D-CT and FFL, and both demonstrated fair interrater agreement. Both modalities underestimated UAO severity, although 4D-CT ratings were significantly more accurate, as determined by QPC similarity, than FFL (-1.06 and -1.46 vs QPC ratings, P = .004). Overall confidence levels were similar for 4D-CT and FFL, but other specialists were significantly less confident in FFL ratings than were otolaryngologists (2.25 and 3.92, P < .0001). CONCLUSION: Although 4D-CT may be more accurate in assessing the degree of UAO in patients with RS, 4D-CT and FFL assessments demonstrate similar reliability. Additionally, 4D-CT may be interpreted with greater confidence by nonotolaryngologists who care for these patients.

Release of Notch activity coordinated by IL-1ß signalling confers differentiation plasticity of airway progenitors via Fosl2 during alveolar regeneration.

While the acquisition of cellular plasticity in adult stem cells is essential for rapid regeneration after tissue injury, little is known about the underlying mechanisms governing this process. Our data reveal the coordination of airway progenitor differentiation plasticity by inflammatory signals during alveolar regeneration. Following damage, interleukin-1ß (IL-1ß) signalling-dependent modulation of Jag1 and Jag2 expression in ciliated cells results in the inhibition of Notch signalling in secretory cells, which drives the reprogramming and acquisition of differentiation plasticity. We identify the transcription factor Fosl2 (also known as Fra2) for secretory cell fate conversion to alveolar type 2 cells that retain the distinct genetic and epigenetic signatures of secretory lineages. We also reveal that human secretory cells positive for KDR (also known as FLK-1) display a conserved capacity to generate alveolar type 2 cells via Notch inhibition. Our results demonstrate the functional role of an IL-1ß-Notch-Fosl2 axis in the fate decision of secretory cells during injury repair, proposing a potential therapeutic target for human lung alveolar regeneration.

Trauma Bay Time Clocks: Influence on Emergency Department Length of Stay.

BACKGROUND: To monitor the time elapsed since patient arrival in the emergency department, Trauma Services at the study institution installed a large digital stopwatch timer placed at the head of each trauma bay on June 5, 2017. This quality improvement endeavor became an essential component of performance evaluation. OBJECTIVE: The purpose of the study is to measure the impact of trauma bay time clocks on emergency department length of stay. METHODS: This is a retrospective before-and-after study of trauma activation patients between June 2015 and May 2019. Two 24-month intervals were compared before and after installation of time clocks. RESULTS: In full activation patients, outcomes of emergency department length of stay ≤50 min (39.2% vs. 61.7%, p < .001) and time to transfer to intensive care unit ≤56 min (45.3% vs. 55.1%, p = .002) were significantly favorable in the postimplementation phase. Time to first computed tomography scan and time to first operating room from arrival to the emergency department were comparable between both phases. For limited activation patients, positive changes were noted in emergency department length of stay ≤87 min (41.4% vs. 60.6%, p < .001), time to first computed tomography scan ≤32 min (47.7% vs. 53.0%, p = .015), and time to transfer to intensive care unit ≤74 min (50.2% vs. 57.2%, p = .008). Time to first operating room remained comparable between two periods. CONCLUSIONS: The study institution improved their provision of immediate care by using time clocks in trauma bays. This is a simple and cost-effective intervention and may benefit similar institutions.