Biologically aware lighting for newborn intensive care.

OBJECTIVE: We designed and implemented a novel neonatal intensive care (NICU) lighting system to support the current understanding of daylight-coupled physiology. METHODS: We created a system that generates wavelengths corresponding to the known blue and violet activation spectra of non-visual opsins. These are known to mediate energy management and related physiologic activity. RESULTS: Light produced by the system spans the visible spectrum, including violet wavelengths that are blocked by modern glazing and not emitted by standard LED fixtures. System features include automated light and dark phases that mimic dawn/dusk. The system also matches length of day seasonality. Spectral composition can be varied to support translational research protocols. Implementation required a comprehensive strategy to inform bedside providers about the value and use of the lighting system. CONCLUSION: Full-spectrum lighting for the NICU is feasible and will inform the optimization of the NICU environment of care to support optimal neonatal growth and development.

Biologically Aware Lighting for Newborn Intensive Care.

Objective: We designed and implemented a novel neonatal intensive care (NICU) lighting system to support current understanding of sunlight-coupled physiology. Methods: We created a system that generates wavelengths corresponding to the known blue and violet activation spectra of non-visual opsins. These are known to mediate energy management and related physiologic activity. Results: Light produced by the system spans the visible spectrum, including violet wavelengths that are blocked by modern glazing and not emitted by standard LED fixtures. System features include automated light and dark phases that mimic dawn/dusk. The system also matches length of day seasonality. Spectral composition can be varied to support translational research protocols. Implementation required a comprehensive strategy to inform bedside providers about the value and use of the lighting system. Conclusion: Full-spectrum lighting for the NICU is feasible and will inform optimization of the NICU environment of care to support optimal neonatal growth and development.

Reactions of Acetonitrile with Trapped, Translationally Cold Acetylene Cations.

The reaction of the acetylene cation (C2H2+) with acetonitrile (CH3CN) is measured in a linear Paul ion trap coupled to a time-of-flight mass spectrometer. C2H2+ and CH3CN are both noted for their astrochemical abundance and predicted relevance for understanding prebiotic chemistry. The observed primary products are c-C3H3+, C3H4+, and C2NH3+. The latter two products react with excess CH3CN to form the secondary product C2NH4+, protonated acetonitrile. The molecular formula of these ionic products can be verified with the aid of isotope substitution via deuteration of the reactants. Primary product reaction pathways and thermodynamics are investigated with quantum chemical calculations and demonstrate exothermic pathways to two isomers of C2NH3+, two isomers of C3H4+, and the cyclopropenyl cation c-C3H3+. This study deepens our understanding of the dynamics and products of a pertinent ion-molecule reaction between two astrochemically abundant molecules in conditions that mimic those of the interstellar medium.

Long-term health-related quality of life and symptom severity following hysterectomy, myomectomy, or uterine artery embolization for the treatment of symptomatic uterine fibroids.

BACKGROUND: Few studies have directly compared different surgical procedures for uterine fibroids with respect to long-term health-related quality of life outcomes and symptom improvement. OBJECTIVE: We examined differences in change from baseline to 1-, 2-, and 3-year follow-up in health-related quality of life and symptom severity among patients who underwent abdominal myomectomy, laparoscopic or robotic myomectomy, abdominal hysterectomy, laparoscopic or robotic hysterectomy, or uterine artery embolization. STUDY DESIGN: The COMPARE-UF registry is a multiinstitutional prospective observational cohort study of women undergoing treatment for uterine fibroids. A subset of 1384 women aged 31 to 45 years who underwent either abdominal myomectomy (n=237), laparoscopic myomectomy (n=272), abdominal hysterectomy (n=177), laparoscopic hysterectomy (n=522), or uterine artery embolization (n=176) were included in this analysis. We obtained demographics, fibroid history, and symptoms by questionnaires at enrollment and at 1, 2, and 3 years posttreatment. We used the UFS-QoL (Uterine Fibroid Symptom and Quality of Life) questionnaire to ascertain symptom severity and health-related quality of life scores among participants. To account for potential baseline differences across treatment groups, a propensity score model was used to derive overlap weights and compare total health-related quality of life and symptom severity scores after enrollment with a repeated measures model. For this health-related quality of life tool, a specific minimal clinically important difference has not been determined, but on the basis of previous research, a difference of 10 points was considered as a reasonable estimate. Use of this difference was agreed upon by the Steering Committee at the time when the analysis was planned. RESULTS: At baseline, women undergoing hysterectomy and uterine artery embolization reported the lowest health-related quality of life scores and highest symptom severity scores compared with those undergoing abdominal myomectomy or laparoscopic myomectomy (P<.001). Those undergoing hysterectomy and uterine artery embolization reported the longest duration of fibroid symptoms with a mean of 6.3 years (standard deviation, 6.7; P<.001). The most common fibroid symptoms were menorrhagia (75.3%), bulk symptoms (74.2%), and bloating (73.2%). More than half (54.9%) of participants reported anemia, and 9.4% women reported a history of blood transfusion. Across all modalities, total health-related quality of life and symptom severity score markedly improved from baseline to 1-year with the largest improvement in the laparoscopic hysterectomy group (Uterine Fibroids Symptom and Quality of Life: delta= [+] 49.2; symptom severity: delta= [-] 51.3). Those undergoing abdominal myomectomy, laparoscopic myomectomy, and uterine artery embolization also demonstrated significant improvement in health-related quality of life (delta= [+]43.9, [+]32.9, [+]40.7, respectively) and symptom severity (delta= [-]41.4, [-] 31.5, [-] 38.5, respectively) at 1 year, and the improvement persisted from baseline for uterine-sparing procedures during second (Uterine Fibroids Symptom and Quality of Life: delta= [+]40.7, [+]37.4, [+]39.3 SS: delta= [-] 38.5, [-] 32.0, [-] 37.7 and third year (Uterine Fibroids Symptom and Quality of Life: delta= [+] 40.9, [+]39.9, [+]41.1 and SS: delta= [-] 33.9, [-]36.5, [-] 33.0, respectively), posttreatment intervals, however with a trend toward decline in degree of improvement from years 1 and 2. Differences from baseline were greatest for hysterectomy; however, this may reflect the relative importance of bleeding in the Uterine Fibroids Symptom and Quality of Life, rather than clinically meaningful symptom recurrence among women undergoing uterus-sparing treatments. CONCLUSION: All treatment modalities were associated with significant improvements in health-related quality of life and symptom severity reduction 1-year posttreatment. However, abdominal myomectomy, laparoscopic myomectomy and uterine artery embolization indicated a gradual decline in symptom improvement and health-related quality of life by third year after the procedure.

Radiofrequency Ablation of Leiomyomas.

Radiofrequency ablation (RFA) of leiomyomas represents a significant advancement in the treatment of this common uterine condition. In the appropriately selected patient, both laparoscopic and transcervical options provide effective treatment for bleeding and bulk symptoms in a uterine-sparing manner. Compared with other minimally invasive leiomyoma treatment options, RFA procedures have comparable or favorable safety profiles, recovery timelines, and reintervention rates. Data on future fertility and pregnancy are limited, although early reports are promising.

A Comparative Analysis of Health-Related Quality of Life 1 Year Following Myomectomy or Uterine Artery Embolization: Findings from the COMPARE-UF Registry.

Objective: To compare 12-month post-treatment health-related quality of life (HR-QoL) and symptom severity (SS) changes among patients with symptomatic uterine fibroids (SUF) not seeking fertility and undergo a hysterectomy, abdominal myomectomy (AM), or uterine artery embolization (UAE). Materials and Methods: The Comparing Options for Management: Patient-Centered Results for Uterine Fibroids (COMPARE-UF) Registry is a multi-institutional prospective observational cohort study of patients treated for SUF. A subset of 1465 women 31-45 years of age, who underwent either hysterectomy (n = 741), AM (n = 446), or UAE (n = 155) were included in this analysis. Demographics, fibroid history, and symptoms were obtained by baseline questionnaires and at 1 year post-treatment. Results were stratified by all treatments and propensity score weighting to adjust for differences in baseline characteristics. Results: Women undergoing UAE reported the lowest baseline HR-QoL and highest SS scores (mean = 40.6 [standard deviation (SD) = 23.8]; 62.3 [SD = 24.2]) followed by hysterectomy (44.3 [24.3]; 59.8 [SD = 24.1]). At 12 months, women who underwent a hysterectomy experienced the largest change in both HR-QoL (48.7 [26.2]) and SS (51.9 [25.6]) followed by other uterine-sparing treatments. Propensity score weighting revealed all treatments produced substantial improvement, with hysterectomy patients reporting the highest HR-QoL score (92.0 [17.8]) compared with myomectomy (86.7 [17.2]) and UAE (82.6 [21.5]) (p < 0.0001). Similarly, hysterectomy patients reported the lowest SS scores (8.2 [15.1]) compared with myomectomy (16.5 [15.1]) and UAE (19.6 [17.5]) (p < 0.0001). Conclusion: All procedures showed improvement in HR-QoL and reduction in SS score at 12 months, hysterectomy showing maximum improvement. Of importance, at 12 months, patients who underwent either a myomectomy or UAE reported comparable symptom relief and HR-QoL. Clinicaltrials.Gov Identifier: NCT02260752.

Point-of-care assessment of combined umbilical arterial and venous lactate: A potential screening test for neonatal acidosis.

OBJECTIVE: To examine the relationship between point-of-care (POC) measurement of combined umbilical arterial and venous (CUAV) lactate and umbilical artery (UA) lactate to determine whether POC assessment of this sample could be an alternative screening modality for neonatal acidosis and aid prediction of neonatal morbidity. METHODS: In this cross-sectional pilot study, UA and CUAV cord blood samples were collected from live, singleton neonates delivered between June and August 2019, at a tertiary care center. UA samples were analyzed for pH and lactate using a blood gas analyzer. CUAV lactate was also assessed on a blood gas analyzer and at the POC. Linear regression was used to determine the correlation between these samples. RESULTS: A total of 152 neonates were included. There was a statistically significant correlation between CUAV lactate concentrations and UA lactate concentrations (R2  = 0.744). Additionally, CUAV lactate concentration measured at the POC was significantly correlated with that measured on a traditional blood gas analyzer (R2  = 0.928). CONCLUSION: POC testing of CUAV lactate is reliable and closely correlated with UA lactate concentrations, making POC testing of CUAV lactate a potential screening test for neonatal acidosis. More data are needed to establish standardization of this test relative to its predictive value in clinical neonatal outcomes.

Velocity-tunable beam of continuously decelerated polar molecules for cold ion-molecule reaction studies.

Producing high densities of molecules is a fundamental challenge for low-temperature, ion-molecule reaction studies. Traveling-wave Stark decelerators promise to deliver high density beams of cold, polar molecules but require non-trivial control of high-voltage potentials. We have overcome this experimental challenge and demonstrate continuous deceleration of ND3 from 385 to 10 m/s, while driving the decelerator electrodes with a 10 kV amplitude sinewave. In addition, we test an alternative slowing scheme, which increases the time delay between decelerated packets of ND3 and non-decelerated molecules, allowing for better energy resolution of subsequent reaction studies. We characterize this source of neutral, polar molecules suitable for energy-resolved reaction studies with trapped ions at cold translational temperatures. We also propose a combined apparatus consisting of the traveling-wave decelerator and a linear ion trap with a time-of-flight mass spectrometer and discuss to what extent it may achieve cold, energy-resolved, ion-neutral reactions.

Using isotopologues to probe the potential energy surface of reactions of C2H2 ++C3H4.

Investigations into bimolecular reaction kinetics probe the details of the underlying potential energy surface (PES), which can help to validate high-level quantum chemical calculations. We utilize a combined linear Paul ion trap with a time-of-flight mass spectrometer to study isotopologue reactions between acetylene cations (C2H2 +) and two isomers of C3H4: propyne (HC3H3) and allene (H2C3H2). In a previous study [Schmid et al., Phys. Chem. Chem. Phys. 22, 20303 (2020)],1 we showed that the two isomers of C3H4 have fundamentally different reaction mechanisms. Here, we further explore the calculated PES by isotope substitution. While isotopic substitution of reactants is a standard experimental tool in the investigation of molecular reaction kinetics, the controlled environment of co-trapped, laser-cooled Ca+ ions allows the different isotopic reaction pathways to be followed in greater detail. We report branching ratios for all of the primary products of the different isotopic species. The results validate the previously proposed mechanism: propyne forms a bound reaction complex with C2H2 +, while allene and C2H2 + perform long-range charge exchange only.

Eggs, dietary cholesterol, choline, betaine, and diabetes risk in the Women's Health Initiative: a prospective analysis.

BACKGROUND: Epidemiological studies have been inconsistent regarding the relations between diabetes risk and the consumption of eggs and nutrients in eggs, such as choline, betaine, and cholesterol. There have been few studies among elderly women. OBJECTIVES: The objective of this study was to examine associations between consumption of eggs, cholesterol, choline, and betaine and the risk of diabetes among elderly US women. METHODS: Multivariable Cox regression was used with data from the prospective Women's Health Initiative. Population attributable risks were calculated. Consumption of eggs alone (not mixed in foods) and nutrients were assessed with an FFQ. Diabetes incidence was defined as the first incidence of self-reported diabetes treated with oral diabetes medication or insulin injections. RESULTS: There were 46,263 women at follow-up baseline. During 13.3 y and 592,984 person-years of follow-up, there were 5480 incident diabetes cases. Higher egg, cholesterol, and choline consumption were each significantly associated with increases in diabetes risk. The associations for eggs and choline were not significant after adjustment for cholesterol consumption. The association for eggs was attenuated after adjustment for non-egg cholesterol consumption, with 1 significant HR in the top consumption quintile (≥3 eggs/wk) of 1.15 (95% CI: 1.05, 1.27; P for linear trend = 0.0001). The population attributable risks for obesity, overweight, consumption of ≥3 eggs/wk, inadequate exercise, and poor diet were 25.0 (95% CI: 22.3, 27.6), 12.8 (95% CI: 11.1, 14.5), 4.2 (95% CI: 2.3, 6.1), 3.5 (95% CI: 1.2, 5.8), and 3.1 (95% CI: 0.5, 5.7), respectively. CONCLUSIONS: As egg consumption increased to ≥3 eggs/wk, there was a steady increase in diabetes risk that may have been due to the cholesterol in the eggs. The population attributable risk for ≥3 eggs/wk was far lower than that for being obese or overweight.

Regional comparison of self-reported late pregnancy cigarette smoking to mass spectrometry analysis.

OBJECTIVE: To report a more accurate prevalence estimate of late pregnancy nicotine exposures. STUDY DESIGN: A cross-sectional study during a 2-month period in 2019. Participants were women delivering in any of the six county maternity hospitals who consented to universal drug testing at the time of delivery as part of routine hospital admission. RESULTS: Of 2531 tested samples, 18.7% tested positive for high levels of cotinine indicating primary smoking or other primary use of tobacco products. Together, 33.0% of the study population tested positive for nicotine exposure during late pregnancy compared to vital records which reported 8.2% cigarette smoking during the third trimester of pregnancy and 10.5% cigarette smoking at any time during pregnancy through maternal self-report. CONCLUSION: Captured vital birth smoking measures vastly underreport actual primary exposures to nicotine products. Vital birth data also fail to capture secondhand exposures which constitute a significant proportion of the population.

Chocolate Candy and Incident Invasive Cancer Risk in the Women's Health Initiative: An Observational Prospective Analysis.

BACKGROUND: Laboratory and animal studies suggest an inverse association between chocolate consumption and the risk of cancer. Epidemiological studies have yielded inconsistent evidence. OBJECTIVE: To assess the association of chocolate candy consumption with incident, invasive total, breast, colorectal, and lung cancers in a large cohort of postmenopausal American women. DESIGN: Prospective cohort study with a mean 14.8-year follow-up. Chocolate candy intake was assessed by food frequency questionnaire. Invasive cancer events were assessed by physician adjudication. PARTICIPANTS/SETTING: The Women's Health Initiative Study enrolled 161,808 postmenopausal women at 40 clinical centers nationwide between 1993 and 1998. Of these women, 114,281 with plausible food frequency or biometric data and no missing data on chocolate candy exposure were selected for analysis. MAIN OUTCOME MEASURES: Cancer risk in quartiles of chocolate candy consumption with the first quartile as referent. STATISTICAL ANALYSES: Multivariable Cox regression was used to calculate hazard ratios and 95% confidence intervals. RESULTS: There were 16,164 documented incident invasive cancers, representing an incidence rate of 17.0 per 100 participants and 12.3 per 1000 person years during follow-up among participants without any preexisting cancers or missing outcome data. There were no statistically significant associations for total invasive cancer (P-linear = .47, P-curvature = .14), or invasive breast cancer (P-linear = .77, P-curvature = .26). For colorectal cancer P-linear was .02, P-curvature was .03, and compared with women eating a 1 oz (28.4 g) chocolate candy serving <1 time per month, the hazard ratio for ≥1.5 times/wk was 1.18 (95% confidence interval: 1.04-1.35). This result may be attributable to the excess adiposity associated with frequent chocolate candy consumption. CONCLUSIONS: In the Women's Health Initiative, there was no significant association between chocolate candy consumption and invasive total or breast cancer. There was a modest 18% higher risk of invasive colorectal cancer for women who ate chocolate candy at least 1.5 times/wk. These results require confirmation.

Nanoparticle Delivery of Proangiogenic Transcription Factors into the Neonatal Circulation Inhibits Alveolar Simplification Caused by Hyperoxia.

Rationale: Advances in neonatal critical care have greatly improved the survival of preterm infants, but the long-term complications of prematurity, including bronchopulmonary dysplasia (BPD), cause mortality and morbidity later in life. Although VEGF (vascular endothelial growth factor) improves lung structure and function in rodent BPD models, severe side effects of VEGF therapy prevent its use in patients with BPD.Objectives: To test whether nanoparticle delivery of proangiogenic transcription factor FOXM1 (forkhead box M1) or FOXF1 (forkhead box F1), both downstream targets of VEGF, can improve lung structure and function after neonatal hyperoxic injury.Methods: Newborn mice were exposed to 75% O2 for the first 7 days of life before being returned to a room air environment. On Postnatal Day 2, polyethylenimine-(5) myristic acid/polyethylene glycol-oleic acid/cholesterol nanoparticles containing nonintegrating expression plasmids with Foxm1 or Foxf1 cDNAs were injected intravenously. The effects of the nanoparticles on lung structure and function were evaluated using confocal microscopy, flow cytometry, and the flexiVent small-animal ventilator.Measurements and Main Results: The nanoparticles efficiently targeted endothelial cells and myofibroblasts in the alveolar region. Nanoparticle delivery of either FOXM1 or FOXF1 did not protect endothelial cells from apoptosis caused by hyperoxia but increased endothelial proliferation and lung angiogenesis after the injury. FOXM1 and FOXF1 improved elastin fiber organization, decreased alveolar simplification, and preserved lung function in mice reaching adulthood.Conclusions: Nanoparticle delivery of FOXM1 or FOXF1 stimulates lung angiogenesis and alveolarization during recovery from neonatal hyperoxic injury. Delivery of proangiogenic transcription factors has promise as a therapy for BPD in preterm infants.

Perimenstrual psychiatric hospitalization: case report and literature review.

Despite the fact that menstrual psychosis has been described since the eighteenth century, there are only about 80 cases reported in the literature. The knowledge and awareness about the disorder remain poor, leading to inaccurate diagnoses and suboptimal treatment. This is the case of a 25-year-old woman with recurrent hospitalizations for mental status changes including psychotic phenomena and catatonia that appeared to follow a cyclical pattern that correlated with her menstrual periods, with complete symptom resolution and return to her usual level of functioning between episodes despite continued treatment with antipsychotic medications. This pattern remitted only after hormonal therapy was initiated. Through this case report, the authors review the literature on the menstrual psychoses, exemplified by this case, and discuss treatment options and prognosis. Menstrual psychosis is an underrecognized condition where psychotic symptoms recur cyclically with menses. Given the poor response that this entity shows to antipsychotic treatment, hormonal therapies have a prominent role.

Respiratory medication use in extremely premature (<29 weeks) infants during initial NICU hospitalization: Results from the prematurity and respiratory outcomes program.

BACKGROUND: The use of medications to treat respiratory conditions of extreme prematurity is often based upon studies of adults or children over 2 years of age. Little is known about the spectrum of medications used or dosing ranges. To inform the design of future studies, we conducted a prospective analysis of respiratory medication exposure among 832 extremely low gestational age neonates. METHODS: The prematurity and respiratory outcomes program (PROP) enrolled neonates less than 29-week gestation from 6 centers incorporating 13 clinical sites. We collected recorded daily "respiratory" medications given along with dosing information through 40-week postmenstrual age or neonatal intensive care unit discharge if earlier. RESULTS: PROP participants were exposed to a wide range of respiratory medications, often at doses beyond published recommendations. Nearly 50% received caffeine and furosemide beyond published recommendations for cumulative dose. Those who developed bronchopulmonary dysplasia were more likely to receive treatment with respiratory medications. However, more than 30% of PROP subjects that did not develop bronchopulmonary dysplasia also were treated with diuretics, systemic steroids, and other respiratory medications. CONCLUSION: Extremely preterm neonates in PROP were exposed to high doses of medications at levels known to generate significant adverse effects. With limited evidence for efficacy, there is an urgent need for controlled trials in this vulnerable patient population.

Respiratory Medications in Infants <29 Weeks during the First Year Postdischarge: The Prematurity and Respiratory Outcomes Program (PROP) Consortium.

OBJECTIVE: To determine patterns of respiratory medications used in neonatal intensive care unit graduates. STUDY DESIGN: The Prematurity Respiratory Outcomes Program enrolled 835 babies <29 weeks of gestation in the first week. Of 751 survivors, 738 (98%) completed at least 1, and 85% completed all 4, postdischarge medication usage in-person/telephone parental questionnaires requested at 3, 6, 9, and 12 months of corrected age. Respiratory drug usage over the first year of life after in neonatal intensive care unit discharge was analyzed. RESULTS: During any given quarter, 66%-75% of the babies received no respiratory medication and 45% of the infants received no respiratory drug over the first year. The most common postdischarge medication was the inhaled bronchodilator albuterol; its use increased significantly from 13% to 31%. Diuretic usage decreased significantly from 11% to 2% over the first year. Systemic steroids (prednisone, most commonly) were used in approximately 5% of subjects in any one quarter. Inhaled steroids significantly increased over the first year from 9% to 14% at 12 months. Drug exposure changed significantly based on gestational age with 72% of babies born at 23-24 weeks receiving at least 1 respiratory medication but only 40% of babies born at 28 weeks. Overall, at some time in the first year, 55% of infants received at least 1 drug including an inhaled bronchodilator (45%), an inhaled steroid (22%), a systemic steroid (15%), or diuretic (12%). CONCLUSION: Many babies born at <29 weeks have no respiratory medication exposure postdischarge during the first year of life. Inhaled medications, including bronchodilators and steroids, increase over the first year.

Application of Human Factors in Neonatal Intensive Care Unit Redesign.

Only recently has physical space design become more widely recognized as playing a critical role in delivery of care, with an emerging body of literature on the application of human factors approaches to design and evaluation. This chapter describes the use of human factors approaches to develop and conduct an evaluation of a proposed Neonatal Intensive Care Unit redesign in a Midwestern children's hospital. Methods included observations and knowledge elicitation from stakeholders to characterize their goals, challenges, and needs. This characterization is integral to informing the design of user-centered solutions, including physical space design. We also describe an approach to evaluating the proposed design that yielded actionable recommendations specific to hospital-driven design goals.