Adult-born neurons maintain hippocampal cholinergic inputs and support working memory during aging.

Adult neurogenesis is reduced during aging and impaired in disorders of stress, memory, and cognition though its normal function remains unclear. Moreover, a systems level understanding of how a small number of young hippocampal neurons could dramatically influence brain function is lacking. We examined whether adult neurogenesis sustains hippocampal connections cumulatively across the life span. Long-term suppression of neurogenesis as occurs during stress and aging resulted in an accelerated decline in hippocampal acetylcholine signaling and a slow and progressing emergence of profound working memory deficits. These deficits were accompanied by compensatory reorganization of cholinergic dentate gyrus inputs with increased cholinergic innervation to the ventral hippocampus and recruitment of ventrally projecting neurons by the dorsal projection. While increased cholinergic innervation was dysfunctional and corresponded to overall decreases in cholinergic levels and signaling, it could be recruited to correct the resulting memory dysfunction even in old animals. Our study demonstrates that hippocampal neurogenesis supports memory by maintaining the septohippocampal cholinergic circuit across the lifespan.  It also provides a systems level explanation for the progressive nature of memory deterioration during normal and pathological aging and indicates that the brain connectome is malleable by experience.

Prevalence of COVID-19 and Risk Factors for Infection Among Pediatric Anesthesia Patients: A Report From the PEACOC Research Network.

BACKGROUND: The Pediatric Anesthesia COVID-19 Collaborative (PEACOC) is a research network to advance the care of children during the pandemic. Here we calculate the prevalence of coronavirus disease 2019 (COVID-19) among children undergoing anesthesia, look at prevalence in the population data from the Centers for Disease Control and Prevention (CDC), and assess independent risk factors for infection. METHODS: This was a multicenter, retrospective, observational study. Children aged 28 days to 18 years scheduled for anesthesia services at 12 centers requiring universal COVID-19 testing from March 29, 2020 to June 30, 2020 were included. COVID-19 positivity rates among those tested were plotted and trends were assessed using the Cochran Armitage test of trend. Independent risk factors were explored using multivariable logistic regression. RESULTS: Data were collected and analyzed on 33,320 anesthesia encounters including 265 children with COVID-19. Over the study period, the rates of infections in the pediatric anesthesia population did not demonstrate a significant trend. In the general population, there was a significant downward trend in infection rates ( P < .001). In exploratory analysis, multivariable risk factors for a COVID-19 positive test were Black/African American race, Hispanic ethnicity, American Society of Anesthesiologists (ASA) physical status III or above, overweight and obese body mass index (BMI), orthopedic cases, abdominal cases, emergency cases, absence of injury and trauma, and West region (all P < .05). CONCLUSIONS: Rates of COVID-19 in pediatric anesthesia patients were consistently lower than in the general population. Independent risk factors of a positive test for children were identified. This is the first time universal testing for a single infectious disease was undertaken on a wide scale. As such, the association of infection with surgical case type or emergency case status is unprecedented.

Continued challenges in pediatric anesthesia during COVID-19 in 2022: An international survey from the pediatric anesthesia COVID-19 collaborative.

INTRODUCTION: This international survey explored the ongoing impact of COVID-19 on pediatric anesthesiology. It assessed COVID-19's impact on the practice of pediatric anesthesiology, staffing, job satisfaction, and retention at the beginning of 2022 and addressed what should be done to ameliorate COVID-19's impact and what initiatives hospitals had implemented. METHODS: This survey focused on five major domains: equipment/medication, vaccination/testing, staffing, burnout, and economic repercussions. Pilot testing for questionnaire clarity was conducted by members of the Pediatric Anesthesia COVID-19 Collaborative. The survey was administered by e-mail to a representative of the 72 collaborative centers. Respondents were instructed to answer based on their institution's practice from February through April of 2022. Descriptive statistics with 95% confidence intervals are reported. RESULTS: Seventy of seventy-two institutions participated in this survey (97% response rate). Fifty-nine (84%) were from the United States, and 11 (16%) included other countries. The majority experienced equipment (68%) and medication (60%) shortages. Many institutions reported staffing shortages in nursing (37%), perioperative staff (27%), and attending anesthesiologists (11%). Sixty-two institutions (89%) indicated burnout was a frequent topic of conversation among pediatric anesthesiologists. Forty-three institutions (61%) reported anesthesiologists leaving current practice and 37 (53%) early retirement. Twenty-eight institutions (40%) canceled elective cases. The major suggestions for improving job retention included improving financial compensation (76%), decreasing clinical time (67%), and increasing flexibility in scheduled clinical time (66%). Only a minority of institutions had implemented the following initiatives: improving financial compensation (19%), increased access to mental health/counseling services (30%), and assistance with child or elder care (7%). At the time of the survey, 34% of institutions had not made any changes. CONCLUSION: Our study found that COVID-19 has continued to impact pediatric anesthesiology. There are major discrepancies between what anesthesiologists believe are important for job satisfaction and faculty retention compared to implemented initiatives. Data from this survey provide insight for institutions and departments for addressing these challenges.

Hemodynamic and anatomic changes after fetal aortic valvuloplasty are associated with procedural success and postnatal biventricular circulation.

BACKGROUND: There are minimal data characterizing the trajectory of left heart growth and hemodynamics following fetal aortic valvuloplasty (FAV). METHODS: This retrospective study included patients who underwent FAV between 2000 and 2019, with echocardiograms performed pre-FAV, immediately post-FAV, and in late gestation. RESULTS: Of 118 fetuses undergoing FAV, 106 (90%) underwent technically successful FAV, of which 55 (52%) had biventricular circulation. Technically successful FAV was associated with improved aortic valve growth (p < 0.001), sustained antegrade aortic arch (AoA) flow (p = 0.02), improved mitral valve (MV) inflow pattern (p = 0.002), and favorable patent foramen ovale (PFO) flow pattern (p = 0.004) from pre-FAV to late gestation. Compared to patients with univentricular outcome, patients with biventricular outcome had less decrement in size of the left ventricle (LV) (p < 0.001) and aortic valve (p = 0.005), as well as more physiologic PFO flow (p < 0.001) and antegrade AoA flow (p < 0.001) from pre-FAV to late gestation. In multivariable analysis, echocardiographic predictors of biventricular outcome were less decline in LV end diastolic dimension (p < 0.001), improved PFO flow (p = 0.004), and sustained antegrade AoA flow (p = 0.002) from pre-FAV to late gestation. CONCLUSION: Stabilization of left heart growth and improved hemodynamics following successful FAV through late gestation are associated with postnatal biventricular circulation.

Coagulation profiles and viscoelastic testing in multisystem inflammatory syndrome in children.

OBJECTIVE: To characterize viscoelastic testing profiles of children with multisystem inflammatory syndrome in children (MIS-C). METHODS: This single-center retrospective review included 30 patients diagnosed with MIS-C from March 1 to September 1, 2020. Thromboelastography (TEG) with platelet mapping was performed in 19 (63%) patients and compared to age- and sex-matched controls prior to cardiac surgery. Relationships between TEG parameters and inflammatory markers were assessed using correlation. RESULTS: Patients with MIS-C had abnormal TEG results compared to controls, including decreased kinetic (K) time (1.1 vs. 1.7 minutes, p < .01), increased alpha angle (75.0° vs. 65.7°, p < .01), increased maximum amplitude (70.8 vs. 58.3 mm, p < .01), and decreased lysis in 30 minutes (Ly30) (1.1% vs. 3.7%, p = .03); consistent with increased clot formation rate and strength, and reduced fibrinolysis. TEG maximum amplitude was moderately correlated with erythrocyte sedimentation rate (ESR) (r = 0.60, p = .02), initial platelet count (r = 0.67, p < .01), and peak platelet count (r = 0.51, p = .03). TEG alpha angle was moderately correlated with peak platelet count (r = 0.54, p = .02). Seventeen (57%) patients received aspirin (ASA) and anticoagulation, five (17%) received only ASA, and three (10%) received only anticoagulation. No patients had a symptomatic thrombotic event. Six (20%) patients had a bleeding event, none of which was major. CONCLUSIONS: Patients with MIS-C had evidence of hypercoagulability on TEG. Increased ESR and platelets were associated with higher clot strength. Patients were prophylactically treated with ASA or anticoagulation with no symptomatic thrombosis or major bleeding. Further multicenter study is required to characterize the rate of thrombosis and optimal thromboprophylaxis algorithm in this patient population.

A survey of the global impact of COVID-19 on the practice of pediatric anesthesia: A study from the pediatric anesthesia COVID-19 Collaborative Group.

BACKGROUND: Pediatric anesthesiology has been greatly impacted by COVID-19 in the delivery of care to patients and to the individual providers. With this study, we sought to survey pediatric centers and highlight the variations in care related to perioperative medicine during the COVID-19 pandemic, including the availability of protective equipment, the practice of pediatric anesthesia, and economic impact. AIM: The aim of the survey was to determine how COVID-19 directly impacted pediatric anesthesia practices during the study period. METHODS: A survey concerning four major domains (testing, safety, clinical management/policy, economics) was developed. It was pilot tested for clarity and content by members of the Pediatric Anesthesia COVID-19 Collaborative. The survey was administered by email to all Pediatric Anesthesia COVID-19 Collaborative members on September 1, 2020. Respondents had six weeks to complete the survey and were instructed to answer the questions based on their institution's practice during September 1 - October 13, 2020. RESULTS: Sixty-three institutions (100% response rate) participated in the COVID-19 Pediatric Anesthesia Survey. Forty-one hospitals (65%) were from the United States, and 35% included other countries. N95 masks were available to anesthesia teams at 91% of institutions (n = 57) (95% CI: 80%-96%). COVID-19 testing criteria of anesthesia staff and guidelines to return to work varied by institution. Structured simulation training aimed at improving COVID-19 safety and patient care occurred at 62% of institutions (n = 39). Pediatric anesthesiologists were economically affected by a reduction in their employer benefits and restriction of travel due to employer imposed quarantine regulations. CONCLUSION: Our data indicate that the COVID-19 pandemic has impacted the testing, safety, clinical management, and economics of pediatric anesthesia practice. Further investigation into the long-term consequences for the specialty is indicated.

Examining the Washington State Breastfeeding-Friendly Policy Development Process Using the Advocacy Coalition Framework.

Objectives Breastfeeding promotion is increasingly recognized as a key public health strategy. Policies can promote breastfeeding by creating supportive environments and addressing challenges. In 2014, the Washington State legislature considered bills to create a voluntary recognition system for breastfeeding-friendly hospitals, clinics, worksites and childcare settings. These Breastfeeding-Friendly Washington (BFW) bills (SB 6298 and HB 2329) did not pass. Methods The purpose of this case study was to analyze the policy development process for the BFW bills using the Advocacy Coalition Framework. Data were collected through semi-structured interviews with key stakeholders in the state policy process, and document review. We used thematic analysis to identify deductive and inductive themes. Results Though all policy actors indicated general support for breastfeeding, two main coalitions (proponents and opponents) diverged in their support of the BFW bills as policy solutions to address barriers to breastfeeding. We conducted 29 interviews with mainly bill proponents, and 54 documents confirmed data about bill opponents. Proponents supported the bills given increasingly strong evidence of breastfeeding's benefits and that public policy could address environmental challenges to breastfeeding. Opponents saw the bills as government overreach into the private matter of choosing to breastfeed. Opposition to the bills came late in the session, and proponents felt opponents' messaging misconstrued the intent of the legislation. Conclusions for Practice Key learnings for developing breastfeeding-friendly state policies include analyzing differences between proponents' and opponents' beliefs, framing advocacy messages beyond individuals and health, expanding the coalition outside of traditional health entities, and anticipating the opposition.

Creating Environments to Support Breastfeeding: The Challenges and Facilitators of Policy Development in Hospitals, Clinics, Early Care and Education, and Worksites.

Objectives Supportive organizational breastfeeding policies can establish enabling environments for breastfeeding. In this qualitative study we identify facilitators and barriers to the development, adoption, and implementation of supportive breastfeeding policies and practices in four influential sectors for breastfeeding women: hospitals, clinics, early care and education settings, and worksites. Methods We interviewed 125 individuals representing 110 organizations in Washington State about their breastfeeding policy development and implementation process between August 2014 and February 2015. Greenhalgh's diffusion of innovations framework guided the interviews and qualitative analysis. Results Breastfeeding policy facilitators across the sectors include national and state laws and regulations, performance tracking requirements, and an increasingly supportive sociopolitical climate; barriers include limited resources and appreciation about the need for breastfeeding policies, and certain organizational characteristics such as workforce age. Despite broad support for breastfeeding, organizations differed on perceptions about the usefulness of written breastfeeding policies. Personal breastfeeding experiences of policy makers and staff affect organizational breastfeeding policies and practices. Conclusions for Practice Supportive organizational systems and environments are built through effective policy development processes; public health can support breastfeeding policy development and assure a coordinated continuum of care by leveraging federal health care policy requirements, building networks to support training and collaboration, and disseminating strategies that reflect the personal nature of breastfeeding.

Expanding the genetics and phenotypes of ocular congenital cranial dysinnervation disorders.

Purpose: To identify genetic etiologies and genotype/phenotype associations for unsolved ocular congenital cranial dysinnervation disorders (oCCDDs). Methods: We coupled phenotyping with exome or genome sequencing of 467 pedigrees with genetically unsolved oCCDDs, integrating analyses of pedigrees, human and animal model phenotypes, and de novo variants to identify rare candidate single nucleotide variants, insertion/deletions, and structural variants disrupting protein-coding regions. Prioritized variants were classified for pathogenicity and evaluated for genotype/phenotype correlations. Results: Analyses elucidated phenotypic subgroups, identified pathogenic/likely pathogenic variant(s) in 43/467 probands (9.2%), and prioritized variants of uncertain significance in 70/467 additional probands (15.0%). These included known and novel variants in established oCCDD genes, genes associated with syndromes that sometimes include oCCDDs (e.g., MYH10, KIF21B, TGFBR2, TUBB6), genes that fit the syndromic component of the phenotype but had no prior oCCDD association (e.g., CDK13, TGFB2), genes with no reported association with oCCDDs or the syndromic phenotypes (e.g., TUBA4A, KIF5C, CTNNA1, KLB, FGF21), and genes associated with oCCDD phenocopies that had resulted in misdiagnoses. Conclusion: This study suggests that unsolved oCCDDs are clinically and genetically heterogeneous disorders often overlapping other Mendelian conditions and nominates many candidates for future replication and functional studies.

Adult-born neurons maintain hippocampal cholinergic inputs and support working memory during aging.

Adult neurogenesis is reduced during aging and impaired in disorders of stress, memory, and cognition though its normal function remains unclear. Moreover, a systems level understanding of how a small number of young hippocampal neurons could dramatically influence brain function is lacking. We examined whether adult neurogenesis sustains hippocampal connections cumulatively across the life span. Long-term suppression of neurogenesis as occurs during stress and aging resulted in an accelerated decline in hippocampal acetylcholine signaling and a slow and progressing emergence of profound working memory deficits. These deficits were accompanied by compensatory reorganization of cholinergic dentate gyrus inputs with increased cholinergic innervation to the ventral hippocampus and recruitment of ventrally projecting neurons by the dorsal projection. While increased cholinergic innervation was dysfunctional and corresponded to overall decreases in cholinergic levels and signaling, it could be recruited to correct the resulting memory dysfunction even in old animals. Our study demonstrates that hippocampal neurogenesis supports memory by maintaining the septohippocampal cholinergic circuit across the lifespan. It also provides a systems level explanation for the progressive nature of memory deterioration during normal and pathological aging and indicates that the brain connectome is malleable by experience.

A cell type-aware framework for nominating non-coding variants in Mendelian regulatory disorders.

Unsolved Mendelian cases often lack obvious pathogenic coding variants, suggesting potential non-coding etiologies. Here, we present a single cell multi-omic framework integrating embryonic mouse chromatin accessibility, histone modification, and gene expression assays to discover cranial motor neuron (cMN) cis-regulatory elements and subsequently nominate candidate non-coding variants in the congenital cranial dysinnervation disorders (CCDDs), a set of Mendelian disorders altering cMN development. We generated single cell epigenomic profiles for ~86,000 cMNs and related cell types, identifying ~250,000 accessible regulatory elements with cognate gene predictions for ~145,000 putative enhancers. Seventy-five percent of elements (44 of 59) validated in an in vivo transgenic reporter assay, demonstrating that single cell accessibility is a strong predictor of enhancer activity. Applying our cMN atlas to 899 whole genome sequences from 270 genetically unsolved CCDD pedigrees, we achieved significant reduction in our variant search space and nominated candidate variants predicted to regulate known CCDD disease genes MAFB, PHOX2A, CHN1, and EBF3 - as well as new candidates in recurrently mutated enhancers through peak- and gene-centric allelic aggregation. This work provides novel non-coding variant discoveries of relevance to CCDDs and a generalizable framework for nominating non-coding variants of potentially high functional impact in other Mendelian disorders.

The Culture Of Health In Early Care And Education: Workers' Wages, Health, And Job Characteristics.

Little is known about the health of the 2.2 million early care and education (ECE) workers responsible for the care, well-being, and success of the approximately ten million children younger than age six enrolled in ECE, or the extent to which ECE environments and employers play a role in workers' health. The purpose of this analysis was to describe the health of an ECE worker sample by wage and by job and center characteristics and to begin to explore the relationships between these factors and workers' health. Our data indicate that ECE workers earn low wages and experience poor mental well-being and high rates of food insecurity. Lower-wage workers worked at centers with more children enrolled in subsidy programs and were more likely to work at centers that did not offer health insurance, paid sick leave, or parental or family leave. Policies and programs that raised workers' wages or mandated the provision of meals to both children and workers could better support teacher health and the quality of ECE for children. Our results suggest that the culture of health in ECE settings and equity-related outcomes could be improved by helping centers provide support and flexibility to teachers (for example, offsetting workers' benefit costs or reducing teacher-to-child ratios to reduce stress) who are managing their own health in the context of demanding work.

Delayed Post Caudal Catheter Placement Pseudomeningocele: A Case Report.

We present a rare case of a 7-month-old infant who developed a pseudomeningocele 16 days after an uneventful caudal catheter placement. The patient did not exhibit neurological deficits or signs of infection, and the mass increased in size with Valsalva maneuver. Pseudomeningocele, an abnormal collection of cerebrospinal fluid around an opening in the dura mater, can be iatrogenic or traumatic. Regional anesthesia is rarely the cause. Recognizing diagnostic features such as the lack of infectious signs and mass compressibility can prevent misdiagnosis and inappropriate invasive treatment.

Diagnosis and Management of a Postpyloric Foreign Body Causing Small Bowel Obstruction in an Infant.

Foreign body ingestion is a common occurrence in the pediatric population and most ingestions resolve with little morbidity. Although radiopaque objects are easily identified on biplane radiographs, radiolucent objects may elude detection, delaying diagnosis. We report a case of a healthy 10-month-old infant who presented with a 5-day history of postprandial vomiting and imaging consistent with small bowel obstruction. On exploratory laparotomy, she was discovered to have a postpyloric foreign body requiring removal through an enterotomy.