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The Society for Pediatric Anesthesia launched the Women's Empowerment and Leadership Initiative (WELI) in 2018 to empower highly productive women pediatric anesthesiologists to achieve equity, promotion, and leadership. WELI is focused on six career development domains: promotion and leadership, networking, conceptualization and completion of projects, mentoring, career satisfaction, and sense of well-being. We sought feedback about whether WELI supported members' career development by surveys emailed in November 2020 (baseline), May 2021 (6 months), and January 2022 (14 months). Program feedback was quantitatively evaluated by the Likert scale questions and qualitatively evaluated by extracting themes from free-text question responses. The response rates were 60.5% (92 of 152) for the baseline, 51% (82 of 161) for the 6-month, and 52% (96 of 185) for the 14-month surveys. Five main themes were identified from the free-text responses in the 6- and 14-month surveys. Members reported that WELI helped them create meaningful connections through networking, obtain new career opportunities, find tools and projects that supported their career advancement and promotion, build the confidence to try new things beyond their comfort zone, and achieve better work-life integration. Frustration with the inability to connect in-person during the coronavirus-19 pandemic was highlighted. Advisors further stated that WELI helped them improve their mentorship skills and gave them insight into early career faculty issues. Relative to the baseline survey, protégés reported greater contributions from WELI at 6 months in helping them clarify their priorities, increase their sense of achievement, and get promoted. These benefits persisted through 14 months. Advisors reported a steady increase in forming new meaningful relationships and finding new collaborators through WELI over time. All the members reported that their self-rated mentoring abilities improved at 6 months with sustained improvement at 14 months. Thus, programs such as WELI can assist women anesthesiologists and foster gender equity in career development, promotion, and leadership.

High-fat diet (HFD) consumption is closely associated with an increased risk of metabolic syndromes (MetS), such as obesity, type 2 diabetes, and cardiovascular diseases (CVDs). Therefore, the consumption of alternative and functional fatty acids to replace saturated fatty acids and/or

Pregnancy rates in β-thalassemia are increasing, but the risk of complications is higher; thus, better understanding of maternal and fetal iron homeostasis in this disorder is needed. HbbTh3/+ (Th3/+) mice model human β-thalassemia. Both the murine and human diseases are characterized by low hepcidin, high iron absorption and tissue iron overload, with concurrent anemia. We hypothesized that disordered iron metabolism in pregnant Th3/+ mice would negatively impact their unborn offspring. The experimental design included these groups: WT dams carrying WT fetuses (WT1); WT dams carrying WT and Th3/+ fetuses (WT2); Th3/+ dams carrying WT and Th3/+ fetuses (Th3/+); and age-matched, non-pregnant adult females. Serum hepcidin was low, and mobilization of splenic and hepatic storage iron was enhanced in all three groups of experimental dams. Intestinal 59Fe absorption was lower in Th3/+ dams (as compared to WT1/2 dams), but splenic 59Fe uptake was higher. Th3/+ dams had hyperferremia, which led to fetal and placenta iron loading, fetal growth restriction and placentomegaly. Notably, Th3/+ dams loaded Th3/+ and WT fetuses, with the latter situation more closely mirroring human circumstances when thalassemic mothers have relatively unaffected (thalassemia trait) offspring. Iron-related oxidative stress, and hypoxia, likely explains impaired fetal growth; enhanced placental erythropoiesis is a probable cause of placental enlargement. Moreover, high fetal liver iron transactivated Hamp; fetal hepcidin downregulated placental FPN expression, limiting placental iron flux and thus mitigating fetal iron loading. Whether gestational iron loading occurs in human thalassemic pregnancy, when blood transfusion can further elevate serum iron, is worth consideration.

Oat (Avena sativa L.) is one of the most widely consumed cereal grains worldwide and is considered as an important cereal crop with high nutritional value and potential health benefits. With different bacterial strains, fermented oat extracts were examined for the antioxidant and antiaging effects on the skin after optimization of extraction conditions. Fermented oats contained high avenanthramides, and its function was investigated on matrix metalloproteinase-1 and collagen expression with human dermal fibroblast cells. After fractionation, butanol layers showed the highest avenanthramides contents. Therefore, the microbial fermentation of oats enhances the quality and content of functional ingredients of oats, which provide natural dietary supplements, antioxidants, and antiaging agents.

Identifying the hemodynamic range that best supports cerebral perfusion using near infrared spectroscopy (NIRS) autoregulation monitoring is a potential physiologic marker for neonatal hypoxic-ischemic encephalopathy (HIE) during therapeutic hypothermia. However, an optimal autoregulation monitoring algorithm has not been identified for neonatal clinical medicine. We tested whether the hemoglobin volume phase (HVP), hemoglobin volume (HVx), and pressure passivity index (PPI) identify changes in autoregulation that are associated with brain injury on MRI or death. The HVP measures the phase difference between a NIRS metric of cerebral blood volume, the total hemoglobin (THb), and mean arterial blood pressure (MAP) at the frequency of maximum coherence. The HVx is the correlation coefficient between MAP and THb. The PPI is the percentage of coherent MAP-DHb (difference between oxygenated and deoxygenated hemoglobin, a marker of cerebral blood flow) epochs in a chosen time period. Neonates cooled for HIE were prospectively enrolled in an observational study in two neonatal intensive care units. In analyses adjusted for study site and encephalopathy level, all indices detected relationships between poor autoregulation in the first 6 h after rewarming with a higher injury score on MRI. Only HVx and PPI during hypothermia and the PPI during rewarming identified autoregulatory dysfunction associated with a poor outcome independent of study site and encephalopathy level. Our findings suggest that the accuracy of mathematical autoregulation algorithms in detecting the risk of brain injury or death may depend on temperature and postnatal age. Extending autoregulation monitoring beyond the standard 72 h of therapeutic hypothermia may serve as a method to provide personalized care by assessing the need for and efficacy of future therapies after the hypothermia treatment phase.

Zinc (Zn) has been reported to mediate leptin secretion, and thus leptin can be an important candidate molecule linking Zn with bone formation. The present study investigated whether zinc deficiency induces leptin secretion by activating a JAK2/STAT3 signaling pathway and leads to osteoblastic apoptosis. MC3T3-E1 cells were incubated for 24 h in normal osteogenic differentiation medium (OSM) or OSM treated with either 1 μM (Low Zn) or 15 μM (High Zn) of ZnCl2 containing 5 μM TPEN (Zn chelator). Our results demonstrated that low Zn stimulated extracellular leptin secretion and increased mRNA and protein expression of leptin in osteoblastic MC3T3-E1 cells. The OB-Rb (long isoform of leptin receptor) expressions were also elevated in osteoblasts under depletion of Zn. Leptin-signaling proteins, JAK2 and p-JAK2 in the cytosol of low Zn osteoblast conveyed leptin signaling, which ultimately induced higher p-STAT3 expression in the nucleus. Apoptotic effects of JAK2/STAT3 pathway were shown by increased caspase-3 in low Zn osteoblasts as well as apoptotic morphological features observed by TEM. Together, these data suggest that low Zn modulates leptin secretion by activating JAK2/STAT3 signaling pathway and induces apoptosis of osteoblastic MC3T3-E1 cells.

BACKGROUND: The Women's Empowerment and Leadership Initiative in the Society for Pediatric Anesthesia was established to support women's efforts to achieve promotion, leadership positions, and equity in pediatric anesthesiology through coaching, mentoring, sponsorship, and networking. Career advancement relies on the establishment of mentoring relationships within institutions and at regional and national levels. Prior to the SARS-CoV-2 (COVID-19) pandemic, networking was primarily conducted at large national meetings. AIMS: When national meetings were canceled by the COVID-19 pandemic, the Women's Empowerment and Leadership Initiative sought to reduce networking barriers by creating a pilot program called "Grow and Advance through Intentional Networking" (GAIN). MATERIALS & METHODS: Monthly 1-h virtual GAIN sessions were developed based on topics requested by the Women's Empowerment and Leadership Initiative members. Faculty facilitated psychologically safe small-group discussions to maximize engagement. RESULTS: We present an overview of our pilot GAIN program, which has been well received by the Women's Empowerment and Leadership Initiative members and met with continuous demand for more sessions. DISCUSSION: Professional networking is critical for career advancement and for developing and maintaining a sense of community and well-being. Early- and mid-career physicians depend on these relationships to facilitate academic productivity and promotion. CONCLUSION: Programs like the Women's Empowerment and Leadership Initiative GAIN are critical for advancing our specialty and supporting the well-being of pediatric anesthesiologists. GAIN addresses barriers to professional networking, including during the COVID-19 pandemic.

OBJECTIVE: The objective of the study was to evaluate the relationship between a panel of candidate plasma biomarkers and (1) death or severe brain injury on magnetic resonance imaging (MRI) and (2) dysfunctional cerebral pressure autoregulation as a measure of evolving encephalopathy. STUDY DESIGN: Neonates with moderate-to-severe hypoxic-ischemic encephalopathy (HIE) at 2 level IV neonatal intensive care units were enrolled into this observational study. Patients were treated with therapeutic hypothermia (TH) and monitored with continuous blood pressure monitoring and near-infrared spectroscopy. Cerebral pressure autoregulation was measured by the hemoglobin volume phase (HVP) index; a higher HVP index indicates poorer autoregulation. Serial blood samples were collected during TH and assayed for Tau, glial fibrillary acidic protein, and neurogranin. MRIs were assessed using National Institutes of Child Health and Human Development scores. The relationships between the candidate biomarkers and (1) death or severe brain injury on MRI (defined as a National Institutes of Child Health and Human Development score of ≥ 2B) and (2) autoregulation were evaluated using bivariate and adjusted logistic regression models. RESULTS: Sixty-two patients were included. Elevated Tau levels on days 2–3 of TH were associated with death or severe injury on MRI (aOR: 1.06, 95% CI: 1.03–1.09; aOR: 1.04, 95% CI: 1.01–1.06, respectively). Higher Tau was also associated with poorer autoregulation (higher HVP index) on the same day (P = .022). CONCLUSIONS: Elevated plasma levels of Tau are associated with death or severe brain injury by MRI and dysfunctional cerebral autoregulation in neonates with HIE. Larger-scale validation of Tau as a biomarker of brain injury in neonates with HIE is warranted.

Obesity is closely associated with low-grade chronic and systemic inflammation and dyslipidemia, and the consumption of omega-3 polyunsaturated fatty acids (n-3 PUFAs) may modulate obesity-related disorders, such as inflammation and dyslipidemia. An emerging research question is to understand the dietary intervention strategy that is more important regarding n-3 PUFA consumption: (1) a lower ratio of n-6/n-3 PUFAs or (2) a higher amount of n-3 PUFAs consumption. To understand the desirable dietary intervention method of n-3 PUFAs consumption, we replaced lard from the experimental diets with either perilla oil (PO) or corn oil (CO) to have identical n-3 amounts in the experimental diets. PO had a lower n-6/n-3 ratio, whereas CO contained higher amounts of PUFAs; it inherently contained relatively lower n-3 but higher n-6 PUFAs than PO. After the 12-week dietary intervention in ob/ob mice, dyslipidemia was observed in the normal chow and CO-fed ob/ob mice; however, PO feeding increased the high density lipoprotein-cholesterol (HDL-C) level; further, not only did the HDL-C level increase, the low density lipoprotein-cholesterol (LDL-C) and triglyceride (TG) levels also decreased significantly after lipopolysaccharide (LPS) injection. Consequently, extra TG accumulated in the liver and white adipose tissue (WAT) of normal chow- or CO-fed ob/ob mice after LPS injection; however, PO consumption decreased serum TG accumulation in the liver and WAT. PUFAs replacement attenuated systemic inflammation induced by LPS injection by increasing anti-inflammatory cytokines but inhibiting pro-inflammatory cytokine production in the serum and WAT. PO further decreased hepatic inflammation and fibrosis in comparison with the ND and CO. Hepatic functional biomarkers (aspartate aminotransferase (AST) and alanine transaminase (ALT) levels) were also remarkably decreased in the PO group. In LPS-challenged ob/ob mice, PO and CO decreased adipocyte size and adipokine secretion, with a reduction in phosphorylation of MAPKs compared to the ND group. In addition, LPS-inducible endoplasmic reticulum (ER) and oxidative stress decreased with consumption of PUFAs. Taken together, PUFAs from PO and CO play a role in regulating obesity-related disorders. Moreover, PO, which possesses a lower ratio of n-6/n-3 PUFAs, remarkably alleviated metabolic dysfunction in LPS-induced ob/ob mice. Therefore, an interventional trial considering the ratio of n-6/n-3 PUFAs may be desirable for modulating metabolic complications, such as inflammatory responses and ER stress in the circulation, liver, and/or WAT.

BACKGROUND Disruption of brain oxygen delivery and consumption after hypoxic-ischemic injury contributes to neonatal mortality and neurological impairment. Measuring cerebral hemodynamic parameters, including cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2 ), is clinically important. PURPOSE Phase-contrast (PC), velocity-selective arterial spin labeling (VSASL), and T2 -relaxation-under-phase-contrast (TRUPC) are magnetic resonance imaging (MRI) techniques that have shown promising results in assessing cerebral hemodynamics in humans. We aimed to test their feasibility in quantifying CBF, OEF, and CMRO2 in piglets. STUDY TYPE Prospective. ANIMAL MODEL Ten neonatal piglets subacutely recovered from global hypoxia-ischemia (N = 2), excitotoxic brain injury (N = 6), or sham procedure (N = 2). FIELD STRENGTH/SEQUENCE VSASL, TRUPC, and PC MRI acquired at 3.0 T. ASSESSMENT Regional CBF was measured by VSASL. Global CBF was quantified by both PC and VSASL. TRUPC assessed OEF at the superior sagittal sinus (SSS) and internal cerebral veins (ICVs). CMRO2 was calculated from global CBF and SSS-derived OEF. End-tidal carbon dioxide (EtCO2 ) levels of the piglets were also measured. Brain damage was assessed in tissue sections postmortem by counting damaged neurons. STATISTICAL TESTS Spearman correlations were performed to evaluate associations among CBF (by PC or VSASL), OEF, CMRO2 , EtCO2 , and the pathological neuron counts. Paired t-test was used to compare OEF at SSS with OEF at ICV. RESULTS Global CBF was 32.1 ± 14.9 mL/100 g/minute and 30.9 ± 8.3 mL/100 g/minute for PC and VSASL, respectively, showing a significant correlation (r = 0.82, P

PURPOSE To validate two neonatal cerebral venous oxygenation (Yv ) MRI techniques, T2 relaxation under phase contrast (TRUPC) and accelerated TRUPC (aTRUPC) MRI, with oxygenation measured with direct blood sampling. METHODS In vivo experiments were performed on seven healthy newborn piglets. For each piglet, a catheter was placed in the superior sagittal sinus to obtain venous blood samples for blood gas oximetry measurement as a gold standard. During the MRI experiment, three to five venous oxygenation levels were achieved in each piglet by varying inhaled O2 content and breathing rate. Under each condition, Yv values of the superior sagittal sinus measured by TRUPC, aTRUPC, and blood gas oximetry were obtained. The Yv quantification in TRUPC and aTRUPC used a standard bovine blood calibration model. The aTRUPC scan was repeated twice to assess its reproducibility. Agreements among TRUPC Yv , aTRUPC Yv , and blood gas oximetry were evaluated by intraclass correlation coefficient (ICC) and paired Student's t-test. RESULTS The mean hematocrit was 23.6 ± 6.5% among the piglets. Across all measurements, Yv values were 51.9 ± 21.3%, 54.1 ± 18.8%, and 53.7 ± 19.2% for blood gas oximetry, TRUPC and aTRUPC, respectively, showing no significant difference between any two methods (P > .3). There were good correlations between TRUPC and blood gas Yv (ICC = 0.801; P < .0001), between aTRUPC and blood gas Yv (ICC = 0.809; P < .0001), and between aTRUPC and TRUPC Yv (ICC = 0.887; P < .0001). The coefficient of variation of aTRUPC Yv was 8.1 ± 9.9%. CONCLUSION The values of Yv measured by TRUPC and aTRUPC were in good agreement with blood gas oximetry. These findings suggest that TRUPC and aTRUPC can provide accurate quantifications of Yv in major cerebral veins.

Obesity is closely associated with low-grade chronic and systemic inflammation and dyslipidemia, and the consumption of omega-3 polyunsaturated fatty acids (

Neonatal hypoxia-ischemia (HI) causes white matter injury that is not fully prevented by therapeutic hypothermia. Adjuvant treatments are needed. We compared myelination in different piglet white matter regions. We then tested whether oleuropein (OLE) improves neuroprotection in 2- to 4-day-old piglets randomized to undergo HI or sham procedure and OLE or vehicle administration beginning at 15 minutes. All groups received overnight hypothermia and rewarming. Injury in the subcortical white matter, corpus callosum, internal capsule, putamen, and motor cortex gray matter was assessed 1 day later. At baseline, piglets had greater subcortical myelination than in corpus callosum. Hypothermic HI piglets had scant injury in putamen and cerebral cortex. However, hypothermia alone did not prevent the loss of subcortical myelinating oligodendrocytes or the reduction in subcortical myelin density after HI. Combining OLE with hypothermia improved post-HI subcortical white matter protection by preserving myelinating oligodendrocytes, myelin density, and oligodendrocyte markers. Corpus callosum and internal capsule showed little HI injury after hypothermia, and OLE accordingly had minimal effect. OLE did not affect putamen or motor cortex neuron counts. Thus, OLE combined with hypothermia protected subcortical white matter after HI. As an adjuvant to hypothermia, OLE may subacutely improve regional white matter protection after HI.

Anesthesiologists must balance demanding clinical workloads with career development goals. Leadership, conflict management, and other skills can improve medical outcomes, reduce stress at work, and increase career satisfaction. However, Medicine in general and Anesthesiology in particular have not traditionally emphasized physician growth in these areas. Coaching utilizes concepts from psychology, adult learning, and adult development theory to support an individual in personal and professional growth through inquiry, reflection, and shared discovery. This manuscript reviews the history and evidence basis for coaching, differentiates coaching from traditional mentorship, and presents some constructs of coaching and working with a coach. An example of a successful pilot program to disseminate coaching skills and support leadership growth among anesthesiologists, the Women's Empowerment and Leadership Initiative within the Society for Pediatric Anesthesia, is described.

Promoting and retaining junior faculty are major challenges for many medical schools. High clinical workloads often limit time for scholarly projects and academic development, especially in anesthesiology. To address this, we created the East/West Visiting Scholars in Pediatric Anesthesia Program (ViSiPAP). The program's goal is to help "jumpstart" academic careers by providing opportunities for national exposure and recognition through invited lectures and collaborative opportunities. East/West ViSiPAP benefits the participating scholars, the home and hosting anesthesia departments, and pediatric anesthesia fellowship training programs. By fostering a sense of well-being and inclusion in the pediatric anesthesia community, East/West ViSiPAP has the potential to increase job satisfaction, help faculty attain promotion, and reduce attrition. Faculty and trainees are exposed to new expertise and role models. Moreover, ViSiPAP provides opportunities for women and underrepresented in medicine faculty. This program can help develop today's junior faculty into tomorrow's leaders in pediatric anesthesia. We advocate for expanding the concept of ViSiPAP to other institutions in academic medicine.

BACKGROUND: Diffusion MRI is routinely used to evaluate brain injury in neonatal encephalopathy. Though abnormal mean diffusivity (MD) is often attributed to cytotoxic edema, the specific contribution from neuronal pathology is unclear. PURPOSE: To determine whether MD from high-resolution diffusion tensor imaging (DTI) can detect variable degrees of neuronal degeneration and pathology in piglets with brain injury induced by excitotoxicity or global hypoxia-ischemia (HI) with or without overt infarction. STUDY TYPE: Prospective. ANIMAL MODEL: Excitotoxic brain injury was induced in 6 neonatal piglets by intrastriatal stereotaxic injection of the glutamate receptor agonist quinolinic acid (QA). Three piglets underwent global HI or sham procedure. Piglets recovered for 20–96 hours before undergoing MRI (n=9). FIELD STRENGTH/SEQUENCE: 3.0T MRI with DTI, T(1)- and T(2)-weighted imaging. ASSESSMENT: MD, fractional anisotropy (FA), and qualitative T(2) injury were measured in putamen and caudate. The cell bodies of normal neurons, degenerating neurons (excitotoxic necrosis, ischemic necrosis, or necrosis-apoptosis cell death continuum), and injured neurons with equivocal degeneration were counted by histopathology. STATISTICAL TESTS: Spearman correlations were used to compare MD and FA to normal, degenerating, and injured neurons. T(2) injury and neuron counts were evaluated by descriptive analysis. RESULTS: The QA insult generated titratable levels of neuronal pathology. In QA, HI, and sham piglets, lower MD correlated with higher ratios of degenerating-to-total neurons (p0.99). Neuron counts were not related to FA (p>0.30) or to qualitative injury from T(2)-weighted MRI. DATA CONCLUSION: MD is more accurate than FA for detecting neuronal degeneration and loss during acute recovery from neonatal excitotoxic and HI brain injury. MD does not reliably detect non-fulminant, nascent, and potentially reversible neuronal injury.

The severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) pandemic has challenged medical systems and clinicians globally to unforeseen levels. Rapid spread of COVID-19 has forced clinicians to care for patients with a highly contagious disease without evidence-based guidelines. Using a virtual modified nominal group technique, the Pediatric Difficult Intubation Collaborative (PeDI-C), which currently includes 35 hospitals from 6 countries, generated consensus guidelines on airway management in pediatric anesthesia based on expert opinion and early data about the disease. PeDI-C identified overarching goals during care, including minimizing aerosolized respiratory secretions, minimizing the number of clinicians in contact with a patient, and recognizing that undiagnosed asymptomatic patients may shed the virus and infect health care workers. Recommendations include administering anxiolytic medications, intravenous anesthetic inductions, tracheal intubation using video laryngoscopes and cuffed tracheal tubes, use of in-line suction catheters, and modifying workflow to recover patients from anesthesia in the operating room. Importantly, PeDI-C recommends that anesthesiologists consider using appropriate personal protective equipment when performing aerosol-generating medical procedures in asymptomatic children, in addition to known or suspected children with COVID-19. Airway procedures should be done in negative pressure rooms when available. Adequate time should be allowed for operating room cleaning and air filtration between surgical cases. Research using rigorous study designs is urgently needed to inform safe practices during the COVID-19 pandemic. Until further information is available, PeDI-C advises that clinicians consider these guidelines to enhance the safety of health care workers during airway management when performing aerosol-generating medical procedures. These guidelines have been endorsed by the Society for Pediatric Anesthesia and the Canadian Pediatric Anesthesia Society.

Background: Cooling delays, temperature outside 33–34°C, and blood pressure below the mean arterial blood pressure with optimal cerebral autoregulation (MAPOPT) might diminish neuroprotection from therapeutic hypothermia in neonates with hypoxic-ischemic encephalopathy (HIE). We hypothesized that longer time to reach temperature

The striatal, primary sensorimotor cortical, and thalamic neurons are highly vulnerable to hypoxia-ischemia (HI) in term newborns. In a piglet model of HI that exhibits similar selective regional vulnerability, we tested the hypothesis that early treatment with sulforaphane, an activator of the Nrf2 transcription factor, protects vulnerable neurons from HI injury. Anesthetized piglets (aged 3–7 days) were subjected to 45 min of hypoxia and 7 min of airway occlusion. At 15 min after resuscitation, the piglets received intravenous vehicle or sulforaphane. At 4 days of recovery, the density of viable neurons in the putamen of vehicle-treated piglets was 31 ± 34% (±SD) that of sham-operated controls. Treatment with sulforaphane significantly increased viability to 77 ± 31%. In the sensorimotor cortex, neuronal viability was also increased; it was 59 ± 35% in the vehicle-treated and 89 ± 15% in the sulforaphane-treated animals. Treatment with sulforaphane increased the nuclear Nrf2 and γ-glu­tamylcysteine synthetase expression at 6 h of recovery in these regions. We conclude that systemic administration of sulforaphane 15 min after HI can induce the translocation of Nrf2 to the nucleus, increase expression of an enzyme involved in glutathione synthesis, and salvage neurons in the highly vulnerable putamen and sensorimotor cortex in a large-animal model of HI. Therefore, targeting Nrf2 activation soon after recovery from HI is a feasible approach for neuroprotection in the newborn brain.

This study investigated the effects of partial replacement of dietary fat with krill oil (KO) or coconut oil (CO) on dyslipidemia and lipid metabolism in rats fed with a high-fat diet (HFD). Sprague Dawley rats were divided into three groups as follows: HFD, HFD + KO, and HFD + CO. The rats were fed each diet for 10 weeks and then intraperitoneally injected with phosphate-buffered saline (PBS) or lipopolysaccharide (LPS) (1 mg/kg). The KO- and CO-fed rats exhibited lower levels of serum lipids and aspartate aminotransferases than those of the HFD-fed rats. Rats fed with HFD + KO displayed significantly lower hepatic histological scores and hepatic triglyceride (TG) content than rats fed with HFD. The KO supplementation also downregulated the adipogenic gene expression in the liver. When treated with LPS, the HFD + KO and HFD + CO groups reduced the adipocyte size in the epididymal white adipose tissues (EAT) relative to the HFD group. These results suggest that KO and CO could improve lipid metabolism dysfunction.

Severe Hemophilia A and Moyamoya arteriopathy (SHAM syndrome) is a rare genetic disorder caused by deletion of portions of the cytogenic band Xq28. A case of SHAM syndrome requiring bilateral cerebral revascularization is described with an emphasis on perioperative management.A 5-year-old boy with severe hemophilia A complicated by factor VIII inhibition presented with right-sided weakness. Imaging revealed multiple strokes and vascular changes consistent with Moyamoya disease. The patient underwent two-staged indirect cerebral bypass revascularizations, first on the left side and several months later on the right. Perioperative management required balancing the administration of agents to prevent coagulopathy and perioperative hemorrhage while mitigating the risk of thromboembolic events associated with bypass surgery. Despite a multidisciplinary effort by the neurosurgery, hematology, critical care, and anesthesiology teams, the post-operative course after both surgeries was complicated by stroke. Fortunately, the patient recovered rapidly to his preoperative functional baseline.We describe a rare case of SHAM syndrome in a pediatric patient who required bilateral revascularizations and discuss strategies for managing the perioperative risk of hemorrhage and stroke. We also review existing literature on SHAM syndrome.

Aim: To evaluate an algorithm that uses an end-tidal carbon dioxide (ETCO2) target of ≥ 30 torr to guide specific changes in chest compression rate and epinephrine administration during cardiopulmonary resuscitation (CPR) in paediatric swine. Methods: Swine underwent asphyxial cardiac arrest followed by resuscitation with either standard or ETCO2-guided algorithm CPR. The standard group received chest compressions at a rate of 100/min and epinephrine every 4 min during advanced life support consistent with the American Heart Association paediatric resuscitation guidelines. In the ETCO2-guided algorithm group, chest compression rate was increased by 10 compressions/min for every minute that the ETCO2 was < 30 torr, and the epinephrine administration interval was decreased to every 2 min if the ETCO2 remained < 30 torr. Short-term survival and physiologic data during active resuscitation were compared. Results: Short-term survival was significantly greater in the ETCO2-guided algorithm CPR group than in the standard CPR group (16/28 [57.1%] versus 4/28 [14.3%]; p = 0.002). Additionally, the algorithm group had higher predicted mean ETCO2, chest compression rate, diastolic and mean arterial pressure, and myocardial perfusion pressure throughout resuscitation. Swine in the algorithm group also exhibited significantly greater improvement in diastolic and mean arterial pressure and cerebral perfusion pressure after the first dose of epinephrine than did those in the standard group. Incidence of resuscitation-related injuries was similar in the two groups. Conclusions: Use of a resuscitation algorithm with stepwise guidance for changes in the chest compression rate and epinephrine administration interval based on a goal ETCO2 level improved survival and intra-arrest hemodynamics in this porcine cardiac arrest model.

Research has shown that women have leadership ability equal to or better than that of their male counterparts, yet proportionally fewer women than men achieve leadership positions and promotion in medicine. The Women's Empowerment and Leadership Initiative (WELI) was founded within the Society for Pediatric Anesthesia (SPA) in 2018 as a multidimensional program to help address the significant career development, leadership, and promotion gender gap between men and women in anesthesiology. Herein, we describe WELI's development and implementation with an early assessment of effectiveness at 2 years. Members received an anonymous, voluntary survey by e-mail to assess whether they believed WELI was beneficial in several broad domains: career development, networking, project implementation and completion, goal setting, mentorship, well-being, and promotion and leadership. The response rate was 60.5% (92 of 152). The majority ranked several aspects of WELI to be very or extremely valuable, including the protege-advisor dyads, workshops, nomination to join WELI, and virtual facilitated networking. For most members, WELI helped to improve optimism about their professional future. Most also reported that WELI somewhat or absolutely contributed to project improvement or completion, finding new collaborators, and obtaining invitations to be visiting speakers. Among those who applied for promotion or leadership positions, 51% found WELI to be somewhat or absolutely valuable to their application process, and 42% found the same in applying for leadership positions. Qualitative analysis of free-text survey responses identified 5 main themes: (1) feelings of empowerment and confidence, (2) acquisition of new skills in mentoring, coaching, career development, and project implementation, (3) clarification and focus on goal setting, (4) creating meaningful connections through networking, and (5) challenges from coronavirus disease 2019 (COVID-19) and the inability to sustain the advisor-protege connection. We conclude that after 2 years, the WELI program has successfully supported career development for the majority of proteges and advisors. Continued assessment of whether WELI can meaningfully contribute to attainment of promotion and leadership positions will require study across a longer period. WELI could serve as a programmatic example to support women's career development in other subspecialties.

Key Points Question How frequently are adolescent patient portal accounts accessed by guardians? Findings In this cross-sectional study including 3429 adolescent accounts across 3 academic institutions, analysis of portal messages found that more than half of adolescent patient portal accounts with outbound messages were accessed by guardians. The percentage of accessed accounts was greater in children aged 13 to 14 years vs those aged 17 to 18 years. Meaning These findings may be useful in guiding health system approaches to protecting adolescent confidentiality when sharing health data via patient portals., Importance Patient portals can be configured to allow confidential communication for adolescents’ sensitive health care information. Guardian access of adolescent patient portal accounts could compromise adolescents’ confidentiality. Objective To estimate the prevalence of guardian access to adolescent patient portals at 3 academic children’s hospitals. Design, Setting, and Participants A cross-sectional study to estimate the prevalence of guardian access to adolescent patient portal accounts was conducted at 3 academic children’s hospitals. Adolescent patients (aged 13-18 years) with access to their patient portal account with at least 1 outbound message from their portal during the study period were included. A rule-based natural language processing algorithm was used to analyze all portal messages from June 1, 2014, to February 28, 2020, and identify any message sent by guardians. The sensitivity and specificity of the algorithm at each institution was estimated through manual review of a stratified subsample of patient accounts. The overall proportion of accounts with guardian access was estimated after correcting for the sensitivity and specificity of the natural language processing algorithm. Exposures Use of patient portal. Main Outcome and Measures Percentage of adolescent portal accounts indicating guardian access. Results A total of 3429 eligible adolescent accounts containing 25 642 messages across 3 institutions were analyzed. A total of 1797 adolescents (52%) were female and mean (SD) age was 15.6 (1.6) years. The percentage of adolescent portal accounts with apparent guardian access ranged from 52% to 57% across the 3 institutions. After correcting for the sensitivity and specificity of the algorithm based on manual review of 200 accounts per institution, an estimated 64% (95% CI, 59%-69%) to 76% (95% CI, 73%-88%) of accounts with outbound messages were accessed by guardians across the 3 institutions. Conclusions and Relevance In this study, more than half of adolescent accounts with outbound messages were estimated to have been accessed by guardians at least once. These findings have implications for health systems intending to rely on separate adolescent accounts to protect adolescent confidentiality., This cross-sectional study uses a natural language processing algorithm to estimate prevalence of access of adolescent patient portal accounts by guardians at 3 academic children's hospitals.

Research is needed to support culturally informed interventions for diverse groups of survivors of intimate partner violence (IPV), such as immigrant women. Researchers, however, often face numerous barriers in recruiting and retaining immigrant survivors of IPV in intervention research. This qualitative study explored strategies to enhance recruitment and retention of immigrant survivors of IPV in intervention research from the perspective of immigrant survivors of IPV and providers serving immigrant women. Forty-six in-depth interviews were conducted with diverse groups of immigrant women (Africans, Asians, and Latinas) and 17 key informant interviews were conducted with providers serving immigrant women. The interviews focused on perceived facilitators and barriers to recruitment and retention including strategies to form partnerships with domestic violence organizations. Data were analyzed using systematic inductive thematic analysis. Participants identified barriers to recruitment such as fear of being judged, lack of familiarity with the recruiter, normalcy of abuse in some cultures, undocumented status, and fear related to legal implications of reporting IPV. Barriers to study retention included lack of motivation, time burden related to study participation, and emotional strain with recounting abuse experience. Participants also shared strategies to facilitate recruitment and retention such as engaging with the community, forming partnerships with domestic violence organizations, using recruiters with similar background and experiences as potential participants, using snowball sampling strategies, recruiting in locations frequently visited by immigrant survivors, providing adequate incentives, ensuring confidentiality, educating survivors about IPV, and conducting periodic check-ins throughout the study period. Findings can be useful for researchers conducting intervention studies with immigrant survivors of IPV.

Cerebral hypoxia-ischemia (HI) compromises the proteasome in a clinically relevant neonatal piglet model. Protecting and activating proteasomes could be an adjunct therapy to hypothermia. We investigated whether chymotrypsin-like proteasome activity differs regionally and developmentally in the neonatal brain. We also tested whether neonatal brain proteasomes can be modulated by oleuropein, an experimental pleiotropic neuroprotective drug, or by targeting a proteasome subunit gene using recombinant adeno-associated virus-9 (AAV). During post-HI hypothermia, we treated piglets with oleuropein, used AAV-short hairpin RNA (shRNA) to knock down proteasome activator 28γ (PA28γ), or enforced PA28γ using AAV-PA28γ with green fluorescent protein (GFP). Neonatal neocortex and subcortical white matter had greater proteasome activity than did liver and kidney. Neonatal white matter had higher proteasome activity than did juvenile white matter. Lower arterial pH 1 h after HI correlated with greater subsequent cortical proteasome activity. With increasing brain homogenate protein input into the assay, the initial proteasome activity increased only among shams, whereas HI increased total kinetic proteasome activity. OLE increased the initial neocortical proteasome activity after hypothermia. AAV drove GFP expression, and white matter PA28γ levels correlated with proteasome activity and subunit levels. However, AAV proteasome modulation varied. Thus, neonatal neocortical proteasomes can be pharmacologically activated. HI slows the initial proteasome performance, but then augments ongoing catalytic activity. AAV-mediated genetic manipulation in the piglet brain holds promise, though proteasome gene targeting requires further development.

Pediatric patients with moyamoya arteriopathy are at high risk for developing new onset transient or permanent neurologic deficits secondary to cerebral hypoperfusion, particularly in the perioperative period. It is therefore essential to carefully manage these patients in a multidisciplinary, coordinated effort to reduce the risk of new permanent neurologic deficits. However, little has been published on perioperative management of pediatric patients with moyamoya, particularly in the early postoperative period during intensive care unit admission. Our pediatric neurocritical care team sought to create a multidisciplinary periprocedural evidence- and consensus-based care pathway for high-risk pediatric patients with moyamoya arteriopathy undergoing anesthesia for any reason to decrease the incidence of periprocedural stroke or transient ischemic attack (TIA). We reviewed the literature to identify risk factors associated with perioperative stroke or TIA among patients with moyamoya and to gather data supporting specific perioperative management strategies. A multidisciplinary team from pediatric anesthesia, neurocritical care, nursing, child life, neurosurgery, interventional neuroradiology, neurology, and hematology created a care pathway for children with moyamoya undergoing anesthesia, classifying them as either high or standard risk, and applying an individualized perioperative management plan to high-risk patients. The incidence of neurologic sequelae before and after pathway implementation will be compared in future studies.

Infants who undergo surgical procedures in the first few months of life are at a higher risk of death or subsequent neurodevelopmental abnormalities. Although the pathogenesis of these outcomes is multifactorial, an understanding of the nature and pathogenesis of brain injury in these infants may assist the anesthesiologist in consideration of their day-to-day practice to minimize such risks. This review will summarize the main types of brain injury in preterm and term infants and their key pathways. In addition, the review will address key potential pathogenic pathways that may be modifiable including intraoperative hypotension, hypocapnia, hyperoxia or hypoxia, hypoglycemia, and hyperthermia. Each of these conditions may increase the risk of perioperative neurological injury, but their long-term ramifications are unclear.

AIM: To examine the relationship between survival and diastolic blood pressure (DBP) throughout resuscitation from paediatric asphyxial cardiac arrest. METHODS: Retrospective, secondary analysis of 200 swine resuscitations. Swine underwent asphyxial cardiac arrest and were resuscitated with predefined periods of basic and advanced life support (BLS and ALS, respectively). DBP was recorded every 30 s. Survival was defined as 20-min sustained return of spontaneous circulation (ROSC). RESULTS: During BLS, DBP peaked between 1–3 min and was greater in survivors (20.0 [11.3, 33.3] mmHg) than in non-survivors (5.0 [1.0, 10.0] mmHg; p

Pediatric traumatic brain injury (TBI) uniquely affects the pediatric population. Abusive head trauma (AHT) is a subset of severe pediatric TBI usually affecting children in the first year of life. AHT is a form of nonaccidental trauma. Sports-related TBI resulting in concussion is a milder form of TBI affecting older children. Current recommended perioperative management of AHT and sports concussions relies on general pediatric TBI guidelines. Research into more specific pediatric TBI screening and management goals is ongoing. This article reviews the epidemiology, mechanisms, clinical signs, and management of AHT and sports-related concussions.

The purpose of this study was to provide validation of intracranial pressure (ICP) derived continuous indices of cerebrovascular reactivity against the lower limit of autoregulation (LLA). Utilizing an intracranial hypertension model within white New Zealand rabbits, ICP, transcranial Doppler (TCD), laser Doppler flowmetry (LDF), and arterial blood pressure were recorded. Data were retrospectively analyzed in a cohort of 12 rabbits with adequate signals for interrogating the LLA. We derived continuous indices of cerebrovascular reactivity: PRx (correlation between ICP and mean arterial pressure [MAP]), PAx (correlation between pulse amplitude of ICP [AMP] and MAP), and Lx (correlation between LDF-based cerebral blood flow [CBF] and cerebral perfusion pressure [CPP]). LLA was derived via piecewise linear regression of CPP versus LDF or CPP versus systolic flow velocity (FVs) plots. We then produced error bar plots for PRx, PAx, and Lx against 2.5 mm Hg bins of CPP, to display the relationship between these indices and the LLA. We compared the CPP values at clinically relevant thresholds of PRx and PAx, to the CPP defined at the LLA. Receiver operating curve (ROC) analysis was performed for each index across the LLA using 2.5 mm Hg bins for CPP. The mean LLA was 51.5 ± 8.2 mm Hg. PRx and PAx error bar plots demonstrate that each index correlates with the LLA, becoming progressively more positive below the LLA. Similarly, CPP values at clinically relevant thresholds of PRx and PAx were not statistically different from the CPP derived at the LLA. Finally, ROC analysis indicated that PRx and PAx predicted the LAA, with areas under the curve (AUCs) of 0.795 (95% confidence interval [CI]: 0.731-0.857, p < 0.0001) and 0.703 (95% CI: 0.631-0.775, p < 0.0001), respectively. Both PRx and PAx generally agree with LLA within this experimental model of intracranial hypertension. Further analysis of clinically used indices of autoregulation across the LLA within pure arterial hypotension models is required.

Intestinal iron transport requires an iron importer (Dmt1) and an iron exporter (Fpn1). The hormone hepcidin regulates iron absorption by modulating Fpn1 protein levels on the basolateral surface of duodenal enterocytes. In the genetic, iron-loading disorder hereditary hemochromatosis (HH), hepcidin production is low and Fpn1 protein expression is elevated. High Fpn1-mediated iron export depletes intracellular iron, causing a paradoxical increase in Dmt1-mediated iron import. Increased activity of both transporters causes excessive iron absorption, thus initiating body iron loading. Logically then, silencing of intestinal Dmt1 or Fpn1 could be an effective therapeutic intervention in HH. It was previously established that Dmt1 knock down prevented iron-loading in weanling Hamp (encoding hepcidin) KO mice (modeling type 2B HH). Here, we tested the hypothesis that Dmt1 silencing combined with dietary iron restriction (which may be recommended for HH patients) will mitigate iron loading once already established. Accordingly, adult Hamp KO mice were switched to a low-iron (LFe) diet and (non-toxic) folic acid-coupled, ginger nanoparticle-derived lipid vectors (FA-GDLVs) were used to deliver negative-control (NC) or Dmt1 siRNA by oral, intragastric gavage daily for 21 days. The LFe diet reduced body iron burden, and experimental interventions potentiated iron losses. For example, Dmt1 siRNA treatment suppressed duodenal Dmt1 mRNA expression (by ~50%) and reduced serum and liver non-heme iron levels (by ~60% and &gt, 85%, respectively). Interestingly, some iron-related parameters were repressed similarly by FA-GDLVs carrying either siRNA, including 59Fe (as FeCl3) absorption (~20% lower), pancreatic non-heme iron (reduced by ~65%), and serum ferritin (decreased 40–50%). Ginger may thus contain bioactive lipids that also influence iron homeostasis. In conclusion, the combinatorial approach of FA-GDLV and Dmt1 siRNA treatment, with dietary iron restriction, mitigated pre-existing iron overload in a murine model of HH.

Iron-deficiency anemia is common worldwide and typically treated by oral iron supplementation. Excess enteral iron, however, may cause pathological outcomes. Developing new repletion approaches is thus warranted. Previous experimentation revealed that select amino acids (AAs) induce trafficking of transporters onto the enterocyte brush-border membrane (BBM) and enhance electrolyte absorption/secretion. Here, we hypothesized that certain AAs would increase the abundance of the main intestinal iron importer, divalent metal-ion transporter 1 (DMT1), on the BBM of duodenal enterocytes, thus stimulating iron absorption. Accordingly, all 20 AAs were screened using an ex vivo duodenal loop/DMT1 western blotting approach. Four AAs (Asp, Gln, Glu, and Gly) were selected for further experimentation and combined into a new formulation. The 4 AAs stimulated 59Fe transport in mouse duodenal epithelial sheets in Ussing chambers (∼4-fold; P < .05). In iron-deprived mice, oral intragastric administration of the 4 AA formulation increased DMT1 protein abundance on the enterocyte BBM by ∼1.5-fold (P < .05). The 4 AAs also enhanced in vivo 59Fe absorption by ∼2-fold (P < .05), even when ∼26 µg of cold iron was included in the transport solution (equal to a human dose of ∼73 mg). Further experimentation using DMT1int/int mice showed that intestinal DMT1 was required for induction of iron transport by the 4 AAs. Select AAs thus enhance iron absorption by inducing DMT1 trafficking onto the apical membrane of duodenal enterocytes. We speculate that further refinement of this new 4 AA formulation will ultimately allow iron repletion at lower effective doses (thus mitigating negative side effects of excess enteral iron).

In traumatic brain injury, longer time spent with a cerebral perfusion pressure (CPP) below the pressure reactivity index (PRx)-derived lower limit of reactivity (LLR) has been shown to be statistically associated with higher mortality. We set out to scrutinise the behaviour of LLR and the methods of its estimation in individual cases by performing retrospective analysis of intracranial pressure (ICP), arterial blood pressure (ABP) and laser Doppler flow (LDF) signals recorded in nine piglets undergoing controlled, terminal hypotension. We focused on the sections of the recordings with stable experimental conditions where a clear breakpoint of LDF/CPP characteristic (LLA) could be identified.In eight of the nine experiments, when CPP underwent a monotonous decrease, the relationship PRx/CPP showed two breakpoints (1 - when PRx starts to rise; 2 - when PRx saturates at PRx 0.3), with LDF-based LLA sitting between them. LLR (CPP at PRx reaching 0.3 in the error bar chart) was close to the lower LLR breakpoint.In conclusion, when CPP has a monotonous decrease, PRx starts worsening before CPP crosses the LLA. A further decrease in CPP below LLA would cause a decrease in CBF, even if the pressure reactivity is not completely lost. This pattern should be taken into account when PRx is used to detect LLA continuously.