Evaluating the usefulness of a wordless picture book for adults with intellectual disabilities about the COVID-19 vaccination programme using co-production: The CAREVIS study.

AIM: To explore the usefulness of a co-designed wordless book showing processes of receiving COVID-19 vaccines designed by, and for, adults with intellectual disabilities. METHODS: A qualitative evaluation of the resource using mixed methods. Semi-structured interviews were conducted with people with intellectual disabilities, carers and health professionals about resource content, and use. This was analysed thematically. A survey was circulated to intellectual disabilities networks to understand resource need, use, sharing and content. RESULTS: Understanding the COVID-19 vaccine was a process, not a single event using one resource. A visual resource had a place in facilitating conversations about vaccines between people with intellectual disabilities and carers. Differing perspectives were expressed regarding personal needs, existing awareness of vaccine programmes and communication preferences. Changes were suggested to improve the suggested storyline and relevance around COVID-19 restrictions changing. CONCLUSION: A visual resource may help conversations about the COVID-19 vaccine for people with intellectual disabilities.

Synthesis of phospholipids in human placenta.

INTRODUCTION: Placental phospholipid synthesis is critical for the expansion of the placental exchange surface area and for production of signaling molecules. Despite their importance, it is not yet established which enzymes involved in the de novo synthesis and remodeling of placental phospholipids are expressed and active in the human placenta. METHODS: We identified phospholipid synthesis enzymes by immunoblotting in placental homogenates and immunofluorescence in placenta tissue sections. Primary human trophoblast (PHT) cells from term healthy placentas (n = 10) were cultured and exposed to 13C labeled fatty acids (16:0, 18:1 and 18:2 n-6, 22:6 n-3) for 2 and 24 h. Three phospholipid classes; phosphatidic acid, phosphatidylcholine, and lysophosphatidylcholine containing 13C fatty acids were quantified by Liquid Chromatography with tandem mass spectrometry (LC/MS-MS). RESULTS: Acyl transferase and phospholipase enzymes were detected in human placenta homogenate and primarily expressed in the syncytiotrophoblast. Three representative 13C fatty acids (16:0, 18:1 and 18:2 n-6) were incorporated rapidly into phosphatidic acid in trophoblasts, but 13C labeled docosahexaenoic acid (DHA; 22:6 n-3) incorporation was not detected. 13C DHA was incorporated into phosphatidylcholine. Lysophosphatidylcholine containing all four 13C labeled fatty acids were found in high abundance. CONCLUSIONS: Phospholipid synthesis and remodeling enzymes are present in the syncytiotrophoblast. 13C labeled fatty acids were rapidly incorporated into cellular phospholipids. 13C DHA was incorporated into phospholipids through the remodeling pathway rather than by de novo synthesis. These understudied pathways are highly active and critical for structure and function of the placenta.

Adaptations to research within the intellectual disability population during the COVID-19 pandemic: Lessons learned from the CAREVIS study.

The COVID-19 pandemic resulted in changes in all areas of clinical practice, including clinical research and within the intellectual disability population. While there have been some benefits from this rapid adoption of change, those involved in research have had to overcome a number of additional challenges. These adaptive changes, which have included the use of technology, closure of social spaces, working with specific groups who are more vulnerable to COVID-19, and mask use impairing communication, have had both positive and negative impacts on research. As the pandemic and related restrictions evolve, it is important to examine the changes that have occurred. In the future, the adoption of a hybrid model in research is likely to be a common approach, establishing a balance between technology and in-person interaction.

Practices and Outcomes from a Prospective, Multicenter Registry for Preterm Newborns with Pulmonary Hypertension.

OBJECTIVE: To describe current treatment practices of preterm infants with early hypoxemic respiratory failure (HRF) and pulmonary hypertension (PH) and their association with patient outcomes. STUDY DESIGN: We developed a prospective, observational, multicenter clinical registry of preterm newborns <34 weeks' gestation with HRF and PH, based on either clinical or echocardiographic evidence during the first 72 hours of life, from 28 neonatal intensive care units in the US from 2017 through 2022. The primary end point was mortality among those who did or did not receive PH-targeted treatment, and the secondary end points included comparisons of major morbidities. Variables were compared using t tests, Wilcoxon rank-sum tests, Fisher exact tests, and χ² tests. RESULTS: We analyzed the results of 224 preterm infants enrolled in the registry. Of which, 84% (188/224) received PH-targeted treatment, most commonly inhaled nitric oxide (iNO). Early mortality in this cohort was high, as 33% (71/224) of this sample died in the first month of life, and 77% of survivors (105/137) developed bronchopulmonary dysplasia. Infants who received PH-targeted treatment had higher oxygenation indices at the time of enrollment (28.16 [IQR: 13.94, 42.5] vs 15.46 [IQR: 11.94, 26.15]; P = .0064). Patient outcomes did not differ between those who did or did not receive PH-targeted therapy. CONCLUSIONS: Early-onset HRF with PH in preterm infants is associated with a high early mortality and a high risk of developing bronchopulmonary dysplasia. iNO is commonly used to treat early-onset PH in preterm infants with HRF. In comparison with untreated infants with lower oxygenation indices, iNO treatment in severe PH may prevent poorer outcomes.

Mixed methods evaluation of pediatric telehealth equity for patients/families who communicate in languages other than English.

Background: Emerging research demonstrates telehealth disparities for patients who communicate in languages other than English. A better understanding of pediatric telehealth use with families who communicate in languages other than English is needed to inform interventions to promote telehealth equity. Methods: We conducted a mixed methods study of telehealth care in a children's hospital health system using electronic health record data for outpatient video telehealth encounters from April 2020 to July 2021 and qualitative interviews with clinical staff and Spanish-speaking parents of telehealth patients. Results: The 16-month study period included 102,387 telehealth encounters; 5% of which were encounters in languages other than English. 83% of languages other than English encounters were with patients/families with a preferred healthcare language of Spanish. 11% of providers conducted ≥10 languages other than English telehealth encounters. This subset of providers conducted 71% of all languages other than English encounters. We conducted 25 interviews with clinical staff (n=13) and parents (n=12). Common themes identified across interviews were: (I) technology barriers affect access to and quality of telehealth; (II) clinical staff and parents are uncertain about the future role of telehealth for patients/families who communicate in languages other than English; (III) the well-known impact of language barriers on in-person healthcare access and quality for patients who communicate in languages other than English is also evident in telehealth. Conclusions: Patients who communicate in languages other than English were underrepresented among telehealth encounters and encounters were concentrated among few providers. Promoting equitable telehealth care requires investment to address technology barriers, increase the readiness of providers and clinics to provide telehealth care in languages other than English, and continued attention to reducing the healthcare impact of language barriers.

Prevalence and Predictors of Pediatric COVID-19 Vaccine Acceptance.

OBJECTIVE: As pediatric COVID-19 vaccine eligibility expands, understanding predictors of vaccine intent is critical to effectively address parental concerns. Objectives included: (1) Evaluate maternal COVID-19 vaccine intent for child(ren) and associated predictors of stated intent; (2) Describe attitudes related to hypothetical vaccination policies; (3) Summarize themes associated with intention to vaccinate child(ren) for COVID-19. STUDY DESIGN: Mothers enrolled in Heath eMoms, a longitudinal survey project, were recruited for this electronic COVID-19 survey. Chi-square analysis was used to compare proportions of respondent characteristics based on vaccination intent. Population survey logistic regression was used for multivariable modeling to assess the independent association between vaccine intent and demographics. RESULTS: The response rate was 65.3% (n = 1884); 44.2% would choose vaccination, 20.3% would not choose vaccination, and 35.5% are unsure whether to have their child(ren) vaccinated for COVID-19. Black mothers (AOR 0.26, 95% CI 0.13, 0.54), respondents with less than high school education (AOR 0.26, 95% 0.12, 0.56) and those in rural areas (AOR 0.28, 95% CI 0.16, 0.48) were less likely to choose vaccination. Commonly cited reasons for vaccine hesitancy include the belief that the vaccine was not tested enough, is not safe, and there are concerns regarding its side effects. CONCLUSION: Over 50% of respondents do not intend or are unsure about their intent to vaccinate their child(ren) for COVID-19 with variability noted by demographics. Opportunities exist for perinatal and pediatric providers to educate pregnant people, parents, and caregivers with a focus on addressing concerns regarding vaccine safety and efficacy. KEY POINTS: · COVID-19 vaccination rates remain suboptimal, especially in the pediatric population, with variation across states.. · We found that the prevalence of vaccine acceptance for young children is low.. · We highlight opportunities for providers to educate parents, focusing on addressing vaccine safety and efficacy..

Human placental lipid content and lipid metabolic enzyme abundance in obesity and across gestation.

Changes in placental lipid metabolism influence the delivery of lipids critical for fetal development and fetal requirements for lipids change across gestation. We hypothesized that placental lipid content and metabolic enzyme protein levels increase across gestation and are elevated in obesity. Placentas (4-40 weeks' gestation) were collected from control (body mass index, BMI = 18.5-24.9, n=37) and obese (BMI > 30, n=19) pregnant women. Trophoblast villous tissue was homogenized and subjected to liquid chromatography tandem mass spectrometry (LC-MS/MS) for phospholipid and triacylglycerol (TAG) analysis and western blot for protein quantification. The placental content of TAG species and nine of 35 identified phosphatidylcholines (PC) were significantly higher (P<0.05) in first trimester (28-79%, 10-47%, respectively). Furthermore, two TAG and three PC differed by maternal BMI and were significantly increased (P<0.05) in the obese group in first trimester (72-87%, 88-119%, respectively). Placental protein abundance of glycerol-2-phosphate (GPAT3) and 1-acyl-sn-glycerol-3-phosphate acyltransferase 2 (AGPAT2), involved in de novo synthesis of PC and TAG, were higher (P<0.05) in the first trimester (66 and 74%, respectively). The protein abundance of the PC-remodeling enzyme PLA2G4c was also higher (63%) in first trimester (P<0.05). In conclusion, the placental content of many phospholipid and TAG species and the protein level of associated synthesis enzymes are higher in first-trimester human placenta. The high PC content may be related to the rapid membrane expansion in early pregnancy and the low placental oxygen tension may promote the accumulation of tissue TAGs in first trimester. Maternal obesity had only limited impact on placental lipid content and metabolic enzyme protein abundance.

Racial and Ethnic Disparities in Medical Complexity and In-Hospital Death Among US-Born VLBW Infants.

BACKGROUND AND OBJECTIVE: To assess the racial and ethnic disparity in the prevalence of complex chronic conditions (CCC) and/or in-hospital death among US-born very low birth weight (VLBW, <1500 g) infants. METHODS: This retrospective, cross-sectional analysis of discharge data from the Kids' Inpatient Database, included VLBW infants born in US hospitals in 2009 and 2012 (n = 554825, weighted n = 573693) exlcuding those with missing demographics. The main outcome was CCC or death. Multiple logistic regression modeling estimated the association of various characteristics with CCC or death, considering race and ethnicity. RESULTS: There was heterogeneity in the association of insurance status and hospital region and experiencing CCC or death when compared across races and ethnicities. Infants of all races and ethnicities had higher odds of CCC or death if they had an operative procedure, were outborn, or had a birth weight of <500 g or 500 g to 999 g compared with 1000 g to 1499 g. Non-Hispanic Black infants <500 g, however, had the highest odds of CCC or death compared with those 1000 g to 1499 g (adjusted odds ratio 67.2, 95% confidence interval, 48.6-93.0), 2.3 times higher than the odds for non-Hispanic White infants (AOR 2.32, 95% confidence interval, 1.57-3.42). CONCLUSIONS: Insurance and region were associated with increased prevalence of CCC or death in certain racial and ethnic groups. Additionally, non-Hispanic Black infants <500 g had >2.3 times the odds of CCC or death compared with non-Hispanic White infants, relative to infants 1000 g to 1499 g. Additional investigation is needed to understand the drivers of these disparities.

Differences in body composition and growth persist postnatally in fetuses diagnosed with severe compared to mild fetal growth restriction.

BACKGROUND: Fetal growth restriction (FGR) is most commonly diagnosed in pregnancy if the estimated fetal weight (EFW) is < 10th%. Those with abnormal Doppler velocimetry, indicating placental insufficiency and pathological FGR, demonstrate reduced fat and lean mass compared to both normally growing fetuses and FGR fetuses with normal Dopplers. The aim of this study was to determine how severity of FGR and abnormal Doppler velocimetry impacts neonatal body composition. Among a cohort of fetuses with an EFW < 10th%, we hypothesized that those with abnormal Dopplers and/or EFW < 3rd% would have persistent reductions in lean body mass and fat mass extending into the neonatal period compared to fetuses not meeting those criteria. METHODS: A prospective cohort of FGR fetuses with an estimated fetal weight (EFW) < 10th% was categorized as severe (EFW < 3rd% and/or abnormal Dopplers; FGR-S) versus mild (EFW 3-10th%; FGR-M). Air Displacement Plethysmography and anthropometrics were performed at birth and/or within the first 6-8 weeks of life. RESULTS: FGR-S versus FGR-M were born one week earlier (P = 0.0024), were shorter (P = 0.0033), lighter (P = 0.0001) with smaller weight-for-age Z-scores (P = 0.0004), had smaller head circumference (P = 0.0004) and lower fat mass (P = 0.01) at birth. At approximately 6-8 weeks postmenstrual age, weight, head circumference, and fat mass were similar but FGR-S neonates were shorter (P = 0.0049) with lower lean mass (P = 0.0258). CONCLUSION: Doppler velocimetry abnormalities in fetuses with an EFW < 10th% identified neonates who were smaller at birth and demonstrated catch-up growth by 6-8 weeks of life that favored fat mass accretion over lean mass and linear growth.

Clinical and Financial Impact of a Diagnostic Stewardship Program for Children with Suspected Central Nervous System Infection.

OBJECTIVE: To investigate the optimal implementation and clinical and financial impacts of the FilmArray Meningitis Encephalitis Panel (MEP) multiplex polymerase chain reaction testing of cerebrospinal fluid (CSF) in children with suspected central nervous system infection. STUDY DESIGN: A pre-post quasiexperimental cohort study to investigate the impact of implementing MEP using a rapid CSF diagnostic stewardship program was conducted at Children's Hospital Colorado (CHCO). MEP was implemented with electronic medical record indication selection to guide testing to children meeting approved use criteria: infants <2 months, immunocompromised, encephalitis, and ≥5 white blood cells/µL of CSF. Positive results were communicated with antimicrobial stewardship real-time decision support. All cases with CSF obtained by lumbar puncture sent to the CHCO microbiology laboratory meeting any of the 4 aforementioned criteria were included with preimplementation controls (2015-2016) compared with postimplementation cases (2017-2018). Primary outcome was time-to-optimal antimicrobials compared using log-rank test with Kaplan-Meier analysis. RESULTS: Time-to-optimal antimicrobials decreased from 28 hours among 1124 preimplementation controls to 18 hours (P < .0001) among 1127 postimplementation cases (72% with MEP testing conducted). Postimplementation, time-to-positive CSF results was faster (4.8 vs 9.6 hours, P < .0001), intravenous antimicrobial duration was shorter (24 vs 36 hours, P = .004), with infectious neurologic diagnoses more frequently identified (15% vs 10%, P = .03). There were no differences in time-to-effective antimicrobials, hospital admissions, antimicrobial starts, or length of stay. Costs of microbiologic testing increased, but total hospital costs were unchanged. CONCLUSIONS: Implementation of MEP with a rapid central nervous system diagnostic stewardship program improved antimicrobial use with faster results shortening empiric therapy. Routine MEP testing for high-yield indications enables antimicrobial optimization with unchanged overall costs.

Placental proteins with predicted roles in fetal development decrease in premature infants.

BACKGROUND: Emerging evidence from animal experiments indicate that factors secreted by the placenta are critical for normal fetal organ development. Our objective was to characterize the umbilical vein and artery proteome in preterm infants and identify proteins that decrease in the neonatal circulation following delivery. METHODS: Cord blood at delivery and neonatal blood at 48-72 h of life was collected in 25 preterm infants. Plasma protein abundance was determined using the SomaLogic platform. RESULTS: When comparing protein levels of umbilical venous to arterial cord blood, 434 proteins were significantly higher indicating placental secretion into the fetal circulation. Moreover, when comparing neonatal blood to umbilical vein levels, 142 proteins were significantly lower. These proteins included Endoplasmic reticulum resident protein 29, CD59, Fibroblast growth factor 2 and Dynactin subunit 2, which are involved in brain development and prevention of brain damage as well as Fibroblast growth factor 1 which prevents lung fibrosis. CONCLUSIONS: The late second trimester human placenta secretes proteins into the fetal circulation which decrease following delivery. Many of these proteins are predicted to be important in the development of fetal organs. Further studies are needed to directly link placental proteins to organ development and poor outcomes in preterm infants. IMPACT: Prematurity remains a leading cause of morbidity and mortality requiring the development of novel treatments. Emerging evidence from animal studies suggest that factors secreted from the placenta may be critical in the development of the fetus. We report that the preterm human placenta secretes an array of proteins into the fetal circulation. Some of these proteins are predicted to be involved in the development of the brain and the lung. When born prematurely, infants are deprived of these placental proteins, which may contribute to their poor outcomes.

Shifting the distribution: modulation of the lipid profile in Yarrowia lipolytica via iron content.

Microbial fermentation offers a sustainable source of fuels, commodity chemicals, and pharmaceuticals, yet strain performance is influenced greatly by the growth media selected. Specifically, trace metals (e.g., iron, copper, manganese, zinc, and others) are critical for proper growth and enzymatic function within microorganisms yet are non-standardized across media formulation. In this work, the effect of trace metal supplementation on the lipid production profile of Yarrowia lipolytica was explored using tube scale fermentation followed by biomass and lipid characterization. Addition of iron (II) to the chemically defined Yeast Synthetic Complete (YSC) medium increased final optical density nearly twofold and lipid production threefold, while addition of copper (II) had no impact. Additionally, dose-responsive changes in lipid distribution were observed, with the percent of oleic acid increasing and stearic acid decreasing as initial iron concentration increased. These changes were reversible with subsequent iron-selective chelation. Use of rich Yeast Peptone Dextrose (YPD) medium enabled further increases in the production of two specialty oleochemicals ultimately reaching 63 and 47% of the lipid pool as α-linolenic acid and cyclopropane fatty acid, respectively, compared to YSC medium. Selective removal of iron (II) natively present in YPD medium decreased this oleochemical production, ultimately aligning the lipid profile with that of non-supplemented YSC medium. These results provide further insight into the proposed mechanisms for iron regulation in yeasts especially as these productions strains contain a mutant allele of the iron regulator, mga2. The work presented here also suggests a non-genetic method for control of the lipid profile in Y. lipolytica for use in diverse applications. KEY POINTS: • Iron supplementation increases cell density and lipid titer in Yarrowia lipolytica. • Iron addition reversibly alters lipid portfolio increasing linolenic acid. • Removal of iron from YPD media provides a link to enhanced oleochemical production.

Fetal Sex Does Not Impact Placental Blood Flow or Placental Amino Acid Transfer in Late Gestation Pregnant Sheep With or Without Placental Insufficiency.

Pregnant sheep have been used to model complications of human pregnancies including placental insufficiency and intrauterine growth restriction. Some of the hallmarks of placental insufficiency are slower uterine and umbilical blood flow rates, impaired placental transport of oxygen and amino acids, and lower fetal arterial concentrations of anabolic growth factors. An impact of fetal sex on these outcomes has not been identified in either human or sheep pregnancies. This is likely because most studies measuring these outcomes have used small numbers of subjects or animals. We undertook a secondary analysis of previously published data generated by our laboratory in late-gestation (gestational age of 133 ± 0 days gestational age) control sheep (n = 29 male fetuses; n = 26 female fetuses; n = 3 sex not recorded) and sheep exposed to elevated ambient temperatures to cause experimental placental insufficiency (n = 23 male fetuses; n = 17 female fetuses; n = 1 sex not recorded). The primary goal was to determine how fetal sex modifies the effect of the experimental insult on outcomes related to placental blood flow, amino acid and oxygen transport, and fetal hormones. Of the 112 outcomes measured, we only found an interaction between fetal sex and experimental insult for the uterine uptake rates of isoleucine, phenylalanine, and arginine. Additionally, most outcomes measured did not show a difference based on fetal sex when adjusting for the impact of placental insufficiency. Exceptions included fetal norepinephrine and cortisol concentrations, which were higher in female compared to male fetuses. For the parameters measured in the current analysis, the impact of fetal sex was not widespread.

3D Fractional Limb Volume Identifies Reduced Subcutaneous and Lean Mass in Fetal Growth Restriction.

OBJECTIVES: Fetal 2D and 3D fractional limb volume (FLV) measurements by ultrasound can detect fetal lean and subcutaneous mass and possibly percent body fat. Our objectives were to 1) compare FLV measurements in fetuses with fetal growth restriction (FGR) versus small for gestational age (SGA) defined by the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG)-supported international Delphi consensus and 2) correlate FLV findings with birth metrics. We hypothesize that FLV measurements will be significantly smaller in FGR versus SGA fetuses and will correlate closer with Ponderal index (PIx) in the neonate than abdominal circumference (AC). METHODS: Patients were categorized as FGR or SGA as defined by ISUOG. Total thigh volume (TTV), volumes of lean mass (LMV), and fat mass volume (FMV) were calculated from 3D acquisitions. Measurements were compared between groups and correlated with birthweight (BW) and PIx (BW/crown-heal length). RESULTS: The FGR group (n = 37) delivered earlier (37/2 versus 38/0; P = .0847), were lighter (2.2 kg versus 2.6 kg; P = .0003) and had lower PIx (0.023 versus 0.025; P = .0013) than SGAs (n = 22). FGRs had reduced TTV (40.6 versus 48.4 cm3 ; P = .0164), FMV (20.8 versus 25.3 cm3 ; P = .0413), and LMV (19.8 versus 23.1 cm3 ; P = .0387). AC had the highest area under the curve (0.69) for FGR. FMV was more strongly associated with PIx than the AC (P = .0032). CONCLUSIONS: The AC and FLV measurements were significantly reduced in FGR fetuses compared to SGAs. While the AC outperformed FLV in predicting FGR, the FLV correlated best with PIx, which holds investigative promise.

Development of a Vitamin K Database for Commercially Available Food in Australia.

Vitamin K content of foods is known to vary substantially by geographical location. In Australia, no Vitamin K database of food exists, thereby creating ambiguity when trying to develop national dietary intake guidelines. This investigation aimed to develop a Vitamin K database for commonly consumed foods that are commercially available in Australian supermarkets. The Vitamin K1 (phylloquinone; PK) and K2 (menaquinone; MK4, MK7) content of 60 foods known to contain Vitamin K were assessed (e.g., vegetables fruits, oils, animal products, dairy and fermented foods). A liquid chromatography with tandem mass spectrometry (LCMS/MS) method was developed and used to measure PK and MKs in different foods with an improved chromatographic separation and detection of Vitamin K's and their analogs. The LOD and LOQ for PK and MK4 was 0.1, 0.5 ng/ml and 0.5, 1.0 ng/ml, respectively. The majority foods contained detectable PK (53/60), about half contained MK4 (31/60), and few contained MK7 (3/60). PK was highest in green leafy vegetables, with moderate amounts in oils. Highest MK4 content was in chicken eggs and meat products such as ham and chicken. This database enables nutritional epidemiologist to estimate dietary Vitamin K intake, especially in Australian cohorts, for a range of health outcomes.

Mapping enzyme catalysis with metabolic biosensing.

Enzymes are represented across a vast space of protein sequences and structural forms and have activities that far exceed the best chemical catalysts; however, engineering them to have novel or enhanced activity is limited by technologies for sensing product formation. Here, we describe a general and scalable approach for characterizing enzyme activity that uses the metabolism of the host cell as a biosensor by which to infer product formation. Since different products consume different molecules in their synthesis, they perturb host metabolism in unique ways that can be measured by mass spectrometry. This provides a general way by which to sense product formation, to discover unexpected products and map the effects of mutagenesis.

Association between vitamin K1 intake and mortality in the Danish Diet, Cancer, and Health cohort.

Reported associations between vitamin K1 and both all-cause and cause-specific mortality are conflicting. The 56,048 participants from the Danish Diet, Cancer, and Health prospective cohort study, with a median [IQR] age of 56 [52-60] years at entry and of whom 47.6% male, were followed for 23 years, with 14,083 reported deaths. Of these, 5015 deaths were CVD-related, and 6342 deaths were cancer-related. Intake of vitamin K1 (phylloquinone) was estimated from a food-frequency questionnaire (FFQ), and its relationship with mortality outcomes was investigated using Cox proportional hazards models. A moderate to high (87-192 µg/d) intake of vitamin K1 was associated with a lower risk of all-cause [HR (95%CI) for quintile 5 vs quintile 1: 0.76 (0.72, 0.79)], cardiovascular disease (CVD)-related [quintile 5 vs quintile 1: 0.72 (0.66, 0.79)], and cancer-related mortality [quintile 5 vs quintile 1: 0.80 (0.75, 0.86)], after adjusting for demographic and lifestyle confounders. The association between vitamin K1 intake and cardiovascular disease-related mortality was present in all subpopulations (categorised according to sex, smoking status, diabetes status, and hypertension status), while the association with cancer-related mortality was only present in current/former smokers (p for interaction = 0.002). These findings suggest that promoting adequate intakes of foods rich in vitamin K1 may help to reduce all-cause, CVD-related, and cancer-related mortality at the population level.

Sorting for secreted molecule production using a biosensor-in-microdroplet approach.

Sorting large libraries of cells for improved small molecule secretion is throughput limited. Here, we combine producer/secretor cell libraries with whole-cell biosensors using a microfluidic-based screening workflow. This approach enables a mix-and-match capability using off-the-shelf biosensors through either coencapsulation or pico-injection. We demonstrate the cell type and library agnostic nature of this workflow by utilizing single-guide RNA, transposon, and ethyl-methyl sulfonate mutagenesis libraries across three distinct microbes (Escherichia coli, Saccharomyces cerevisiae, and Yarrowia lipolytica), biosensors from two organisms (E. coli and S. cerevisiae), and three products (triacetic acid lactone, naringenin, and L-DOPA) to identify targets improving production/secretion.

Comparison of subdural grid and stereoelectroencephalography in a cohort of pediatric patients.

OBJECTIVE: To compare adverse events and outcomes between stereoelectroencephalography (SEEG) and subdural electrode (SDE) implantation in children. METHODS: This was a retrospective analysis of 108 patients who underwent intracranial monitoring with SEEG or SDE implantation at Children's Hospital Colorado between January 2011 and June 2019. RESULTS: There were 47 patients who underwent 53 SEEG implantations and 61 patients who underwent 64 SDE implantations, with an average age of 12.45 years (range: 1.22-19.96 years). Post-implantation imaging was performed in all SEEG implantations and 42 SDE implantations. 38 % and 88 % of SEEG and SDE implantations, respectively, had a hemorrhage of any kind (p < 0.01). Clinically significant hemorrhages did not differ between the two groups, though one death was reported in the SEEG group. No patient undergoing SEEG implantation received blood products compared to 20 % of SDE patients (p < 0.01). The rate of infection in SEEG patients was 4% compared to 33 % for SDE patients (p = 0.01). Resection was completed in 60 % of SEEG patients versus 93 % for SDE patients (p < 0.01). Rate of seizure response was not significantly different between the two groups, with 81 % and 71 % of SEEG and SDE patients, respectively, reaching Engel class I or II at 12 months (p = 0.76). SIGNIFICANCE: In pediatric patients at a single institution, SEEG is associated with less adverse effects overall yet similar rates of seizure freedom compared to SDE implantation. This includes significantly lower rates of asymptomatic hemorrhage, infection and need for blood transfusion associated with SEEG monitoring. There was no statistical difference in clinically significant hemorrhages between the two groups, although rare in both.

Clinical Impact of the Expanded BioFire Blood Culture Identification 2 Panel in a U.S. Children's Hospital.

The BioFire blood culture identification (BCID) panel decreases time to pathogen identification and time to optimal antimicrobial therapy. The BioFire blood culture identification 2 (BCID2) panel is an expanded panel with 17 additional targets and resistance genes; however, there are limited data on its impact in pediatric patients. We compared the BioFire BCID2 panel and the BCID panel by assaying BCID2 simultaneously with the current standard of care on 191 consecutive blood culture specimens at Children's Hospital Colorado. The primary outcome was equivalence, measured as percent agreement between the two panels and standard culture. The theoretical reduction in time to optimal therapy was calculated overall, with subanalyses performed on Enterococcus species and Gram-negative resistance genes. The percent agreement was equivalent between the two panels, with BCID at 98% (95% confidence interval [CI], 95 to 100%) and BCID2 at 97% (95% CI, 93 to 99%); the difference was 1.2% (95% CI, -0.8, 3.1%; P < 0.0001). There was not a significant reduction in time to theoretical optimal therapy with BCID2 compared to BCID for all cultures (reduction of 9 h, P = 0.3). Notably, 13 Enterococcus faecalis isolates were detected on BCID2, which would have resulted in a theoretical reduction in time to optimal antimicrobial therapy of 34 h (P = 0.0046). Five CTX-M genes were detected for enteric bacteria. The BioFire BCID2 panel had equal rates of detection compared to the BioFire BCID panel in pediatric patients. It had the advantage of detecting more organisms at the species level, and significantly reducing time to theoretical optimal antimicrobial therapy for Enterococcus faecalis. With the additional resistance genes, it also has the potential to impact care with earlier identification of resistant enteric pathogens. IMPORTANCE The BioFire BCID2 panel is an accurate panel that is equivalent to the BioFire BCID panel compared to standard culture. The BioFire BCID2 panel offers several advantages over the BioFire BCID panel, including enterococcal species identification, Gram-negative resistance gene detection, Salmonella identification, and the added mecA/mecC and SCCmec right extremity junction (MREJ) target for better Staphylococcus aureus and coagulase-negative Staphylococcus (CoNS) differentiation. Most importantly, it provides additional clinical impact with the potential to decrease the time to optimal antimicrobial therapy compared to the BioFire BCID panel, with likely further impact at institutions with a higher prevalence of Gram-negative resistance.