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A correction to the article "The Impact of Political Connections on Donations to Chinese NGOs," that was published in the 2016 issue is presented

Select Drug Category Opiates/Opioids Topic Tolerance/Dependence Abstract Detail Clinical - Epidemiology Abstract Category Original Research Characterize the relationship between intraoperative opioid administration and postoperative pain and opioid requirements. We conducted a retrospective cohort study of 61,250 adult patients who received non-cardiac surgery under general anesthesia at a quaternary care center between 2016 and 2020. The exposure variable was intraoperative fentanyl and intraoperative hydromorphone average effect site concentration. The primary study outcomes were maximal pain score during post-anesthesia care unit (PACU) stay and cumulative opioids administered in the PACU in morphine milligram equivalents (MME). Secondary outcomes included frequency of uncontrolled pain at 24 hours, new instances of chronic pain diagnosis, total opioid use at 24 hours and in-hospital, opioid prescriptions at 30, 90, and 180 postoperative days, frequency of new persistent opioid use, maximal pain score in the first 24 hours and in-hospital, and incidence of opioid related complications in PACU. We used multivariate propensity weighting to control for confounding and estimated the counterfactual difference in outcomes after administration of an additional 100 mcg fentanyl or 500 mcg hydromorphone intraoperatively. Increased intraoperative fentanyl and intraoperative hydromorphone were both associated with reduced maximum pain scores in the PACU. Both exposures were also associated with a reduced probability and reduced total dosage of opioid administration in the PACU. We found that increased fentanyl administration in particular was associated with lower frequency of uncontrolled pain, decreased chronic pain at 3-months, fewer opioid prescriptions at 30-, 90-, and 180-days, and decreased persistent opioid use, without significant increases in side effects. Our results show that intraoperative opioid administration is significantly associated with short- and long-term effects on post-operative pain and opioid outcomes. Contrary to prevailing trends, reduced opioid administration during surgery may have the unintended consequence of increasing postoperative pain and opioid consumption. Our analysis suggests that significant improvements in long-term outcomes might be achieved by optimizing opioid administration during surgery. [ABSTRACT FROM AUTHOR]

Wastewater-based epidemiology (WBE) is an environmental approach to monitor community health through the analysis of sewage. The COVID-19 pandemic catalyzed scientists and public health professionals to revisit WBE as a tool to optimize resource allocation to mitigate disease spread and prevent outbreaks. Some studies have highlighted the value of WBE programs that coordinate with public health professionals; however, the details necessary for implementation are not well-characterized. To respond to this knowledge gap, this article documents the framework of a successful WBE program in Arizona, titled Wastewater Analysis for Tactical Epidemiological Response Systems (WATERS), detailing the developed structure and methods of communication that enabled public health preparedness and response actions. This communication illustrates how program operations were employed to reduce outbreak severity. The structure outlined here is customizable and may guide other programs in the implementation of WBE as a public health tool., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Brosky, Prasek, Innes, Pepper, Miranda, Brierley, Slinski, Polashenski, Betancourt, Gronbach, Gomez, Neupane, Johnson, Weiss, Yaglom, Engelthaler, Hepp, Crank, Gerrity, Stewart and Schmitz.)

Competing Interests: The authors have no conflicts of interest to disclose.

Background: Preoperative knowledge of surgical risks can improve perioperative care and patient outcomes. However, assessments requiring clinician examination of patients or manual chart review can be too burdensome for routine use., Methods: We conducted a multicentre retrospective study of 243 479 adult noncardiac surgical patients at four hospitals within the Mass General Brigham (MGB) system in the USA. We developed a machine learning method using routinely collected coding and patient characteristics data from the electronic health record which predicts 30-day mortality, 30-day readmission, discharge to long-term care, and hospital length of stay., Results: Our method, the Flexible Surgical Set Embedding (FLEX) score, achieved state-of-the-art performance to identify comorbidities that significantly contribute to the risk of each adverse outcome. The contributions of comorbidities are weighted based on patient-specific context, yielding personalised risk predictions. Understanding the significant drivers of risk of adverse outcomes for each patient can inform clinicians of potential targets for intervention., Conclusions: FLEX utilises information from a wider range of medical diagnostic and procedural codes than previously possible and can adapt to different coding practices to accurately predict adverse postoperative outcomes., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The maternal mortality rate for non-Hispanic Black birthing people is 69.9 deaths per 100,000 live births compared with 26.6 deaths per 100,000 live births for non-Hispanic White birthing people. Black pregnancy-related mortality has been underrepresented in research and the media; however, there is growing literature on the role of racism in health disparities. Those who provide care to Black patients should increase their understanding of racism's impact and take steps to center the experiences and needs of Black birthing people., Competing Interests: Disclosure The author reports no conflicts of interest or financial disclosures. The author reports no funding sources., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The role of parathyroid hormone (PTH)-related protein (PTHrP) in breast cancer remains controversial, with reports of PTHrP inhibiting or promoting primary tumor growth in preclinical studies. Here, we provide insight into these conflicting findings by assessing the role of specific biological domains of PTHrP in tumor progression through stable expression of PTHrP (-36-139aa) or truncated forms with deletion of the nuclear localization sequence (NLS) alone or in combination with the C-terminus. Although the full-length PTHrP molecule (-36-139aa) did not alter tumorigenesis, PTHrP lacking the NLS alone accelerated primary tumor growth by downregulating p27, while PTHrP lacking the NLS and C-terminus repressed tumor growth through p27 induction driven by the tumor suppressor leukemia inhibitory factor receptor (LIFR). Induction of p27 by PTHrP lacking the NLS and C-terminus persisted in bone disseminated cells, but did not prevent metastatic outgrowth, in contrast to the primary tumor site. These data suggest that the PTHrP NLS functions as a tumor suppressor, while the PTHrP C-terminus may act as an oncogenic switch to promote tumor progression through differential regulation of p27 signaling., (© 2024. The Author(s).)

Background: Individual adverse social determinants of health are associated with increased risk of diabetes in pregnancy, but the relative influence of neighborhood or community-level social determinants of health is unknown., Objective: This study aimed to determine whether living in neighborhoods with greater socioeconomic disadvantage, food deserts, or less walkability was associated with having pregestational diabetes and developing gestational diabetes., Study Design: We conducted a secondary analysis of the prospective Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be. Home addresses in the first trimester were geocoded at the census tract level. The exposures (modeled separately) were the following 3 neighborhood-level measures of adverse social determinants of health: (1) socioeconomic disadvantage, defined by the Area Deprivation Index and measured in tertiles from the lowest tertile (ie, least disadvantage [T1]) to the highest (ie, most disadvantage [T3]); (2) food desert, defined by the United States Department of Agriculture Food Access Research Atlas (yes/no by low income and low access criteria); and (3) less walkability, defined by the Environmental Protection Agency National Walkability Index (most walkable score [15.26-20.0] vs less walkable score [<15.26]). Multinomial logistic regression was used to model the odds of gestational diabetes or pregestational diabetes relative to no diabetes as the reference, adjusted for age at delivery, chronic hypertension, Medicaid insurance status, and low household income (<130% of the US poverty level)., Results: Among the 9155 assessed individuals, the mean Area Deprivation Index score was 39.0 (interquartile range, 19.0-71.0), 37.0% lived in a food desert, and 41.0% lived in a less walkable neighborhood. The frequency of pregestational and gestational diabetes diagnosis was 1.5% and 4.2%, respectively. Individuals living in a community in the highest tertile of socioeconomic disadvantage had increased odds of entering pregnancy with pregestational diabetes compared with those in the lowest tertile (T3 vs T1: 2.6% vs 0.8%; adjusted odds ratio, 2.52; 95% confidence interval, 1.41-4.48). Individuals living in a food desert (4.8% vs 4.0%; adjusted odds ratio, 1.37; 95% confidence interval, 1.06-1.77) and in a less walkable neighborhood (4.4% vs 3.8%; adjusted odds ratio, 1.33; 95% confidence interval, 1.04-1.71) had increased odds of gestational diabetes. There was no significant association between living in a food desert or a less walkable neighborhood and pregestational diabetes, or between socioeconomic disadvantage and gestational diabetes., Conclusion: Nulliparous individuals living in a neighborhood with higher socioeconomic disadvantage were at increased odds of entering pregnancy with pregestational diabetes, and those living in a food desert or a less walkable neighborhood were at increased odds of developing gestational diabetes, after controlling for known covariates., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Polymorphisms in genes responsible for the metabolism and transport of tacrolimus have been demonstrated to influence clinical outcomes for patients following allogeneic hematologic stem cell transplant (allo-HSCT). However, the clinical impact of germline polymorphisms specifically for oral formulations of tacrolimus is not fully described. Methods: To investigate the clinical impact of genetic polymorphisms in CYP3A4 , CYP3A5 , and ABCB1 on oral tacrolimus pharmacokinetics and clinical outcomes, we prospectively enrolled 103 adult patients receiving oral tacrolimus for the prevention of graft-versus-host disease (GVHD) following allo-HSCT. Patients were followed in the inpatient and outpatient phase of care for the first 100 days of tacrolimus therapy. Patients were genotyped for CYP3A5 *3 (rs776746), CYP3A4 *1B (rs2740574), ABCB1 exon 12 (rs1128503), ABCB1 exon 21 (rs2032582), ABCB1 exon 26 (rs1045642). Results: Expression of CYP3A5 *1 was highly correlated with tacrolimus pharmacokinetics in the inpatient phase of care ( p < 0.001) and throughout the entirety of the study period ( p < 0.001). Additionally, Expression of CYP3A5 *1 was associated with decreased risk of developing AKI as an inpatient ( p = 0.06). Variants in ABCB1 were not associated with tacrolimus pharmacokinetics in this study. We were unable to discern an independent effect of CYP3A4 *1B or *22 in this population. Conclusion: Expression of CYP3A5 *1 is highly influential on the pharmacokinetics and clinical outcomes for patients receiving oral tacrolimus as GVHD prophylaxis following allo-HSCT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Seligson, Zhang, Zemanek, Johnson, VanGundy, Wang, Phelps, Roddy, Hofmeister, Li and Poi.)

Background: Infants under spinal anesthesia appear to be sedated despite the absence of systemic sedative medications. In this prospective observational study, we investigated the electroencephalogram (EEG) of infants under spinal anesthesia and hypothesized that we would observe EEG features similar to those seen during sleep., Methods: We computed the EEG power spectra and spectrograms of 34 infants undergoing infraumbilical surgeries under spinal anesthesia (median age 11.5 weeks postmenstrual age, range 38-65 weeks postmenstrual age). Spectrograms were visually scored for episodes of EEG discontinuity or spindle activity. We characterized the relationship between EEG discontinuity or spindles and gestational age, postmenstrual age, or chronological age using logistic regression analyses., Results: The predominant EEG patterns observed in infants under spinal anesthesia were slow oscillations, spindles, and EEG discontinuities. The presence of spindles, observed starting at about 49 weeks postmenstrual age, was best described by postmenstrual age ( P =.002) and was more likely with increasing postmenstrual age. The presence of EEG discontinuities, best described by gestational age ( P = .015), was more likely with decreasing gestational age. These age-related changes in the presence of spindles and EEG discontinuities in infants under spinal anesthesia generally corresponded to developmental changes in the sleep EEG., Conclusions: This work illustrates 2 separate key age-dependent transitions in EEG dynamics during infant spinal anesthesia that may reflect the maturation of underlying brain circuits: (1) diminishing discontinuities with increasing gestational age and (2) the appearance of spindles with increasing postmenstrual age. The similarity of these age-dependent transitions under spinal anesthesia with transitions in the developing brain during physiological sleep supports a sleep-related mechanism for the apparent sedation observed during infant spinal anesthesia., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2023 International Anesthesia Research Society.)

Preoperative knowledge of expected postoperative pain can help guide perioperative pain management and focus interventions on patients with the greatest risk of acute pain. However, current methods for predicting postoperative pain require patient and clinician input or laborious manual chart review and often do not achieve sufficient performance. We use routinely collected electronic health record data from a multicenter dataset of 234,274 adult non-cardiac surgical patients to develop a machine learning method which predicts maximum pain scores on the day of surgery and four subsequent days and validate this method in a prospective cohort. Our method, POPS, is fully automated and relies only on data available prior to surgery, allowing application in all patients scheduled for or considering surgery. Here we report that POPS achieves state-of-the-art performance and outperforms clinician predictions on all postoperative days when predicting maximum pain on the 0-10 NRS in prospective validation, though with degraded calibration. POPS is interpretable, identifying comorbidities that significantly contribute to postoperative pain based on patient-specific context, which can assist clinicians in mitigating cases of acute pain., (© 2023. The Author(s).)

Background: Opioid use disorder is a leading cause of death through the year postpartum., Objective: This study aimed to identify the association of neighborhood-level social determinants of health and prenatal opioid use disorder treatment receipt with the outcomes of medication treatment for opioid use disorder through the year postpartum among a cohort of birthing people., Study Design: This was a population-based retrospective cohort study that used state Medicaid claims and enrollment data for the 1690 individuals who delivered a live infant between July 1, 2016 and December 31, 2020 and received medication for opioid use disorder at delivery. The primary exposure was the state Health Opportunity Index, a composite measure of social determinants of health linked at the census-tract level. Secondary exposures included comprehensiveness of opioid use disorder treatment and duration of medication treatment for opioid use disorder received prenatally. Outcomes included the duration and continuity of postpartum medication treatment for opioid use disorder, operationalized as the time from delivery to the discontinuation of medication treatment for opioid use disorder, and percentage of days covered by medication treatment for opioid use disorder within the 12 months after delivery, respectively., Results: Within the study sample, 711 deliveries were to birthing people in the lowest state Health Opportunity Index tercile (indicating high burden of negative social determinants of health), 647 in the middle state Health Opportunity Index tercile, and 332 in the highest state Health Opportunity Index tercile. Using stepwise multivariable regression (Cox proportional hazards and negative binomial models) guided by a socioecological framework, prenatal receipt of more comprehensive opioid use disorder treatment and/or longer duration of prenatal medication treatment for opioid use disorder was associated with improved 1-year postpartum opioid use disorder treatment outcomes (duration and continuity of medication treatment for opioid use disorder). When the state Health Opportunity Index was added to the models, these significant associations remained stable, with the state Health Opportunity Index not demonstrating an association with the outcomes (duration hazard ratio, 1.39; 95% confidence interval, 0.551-3.512; continuity relative risk, 1.024; 95% confidence interval, 0.323-3.247)., Conclusion: Targeted efforts at expanding access to and quality of evidence-based opioid use disorder treatments for reproductive-age people across the life course should be prioritized within the spectrum of work aimed at eradicating disparities in pregnancy-related mortality., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To examine whether exposure to community or neighborhood socioeconomic disadvantage as measured by the ADI (Area Deprivation Index) is associated with risk of abnormal birth weight among nulliparous individuals with singleton gestations., Methods: This was a secondary analysis from the prospective cohort NuMoM2b study (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be). Participant addresses at cohort enrollment between 6 and 13 weeks of gestation were geocoded at the Census tract level and linked to the 2015 ADI. The ADI, which incorporates the domains of income, education, employment, and housing quality into a composite national ranking of neighborhood socioeconomic disadvantage, was categorized by quartiles (quartile 1, least disadvantaged, reference; quartile 4, most disadvantaged). Outcomes were large for gestational age (LGA; birth weight at or above the 90th percentile) and small for gestational age (SGA; birth weight below the 10th percentile) compared with appropriate for gestational age (AGA; birth weight 10th-90th percentile) as determined with the 2017 U.S. natality reference data, standardized for fetal sex. Multinomial logistic regression models were adjusted for potential confounding variables., Results: Of 8,983 assessed deliveries in the analytic population, 12.7% (n=1,143) were SGA, 8.2% (n=738) were LGA, and 79.1% (n=7,102) were AGA. Pregnant individuals living in the highest ADI quartile (quartile 4, 17.8%) had an increased odds of delivering an SGA neonate compared with those in the lowest referent quartile (quartile 1, 12.4%) (adjusted odds ratio [aOR] 1.32, 95% CI 1.09-1.55). Pregnant individuals living in higher ADI quartiles (quartile 2, 10.3%; quartile 3, 10.7%; quartile 4, 9.2%) had an increased odds of delivering an LGA neonate compared with those in the lowest referent quartile (quartile 1, 8.2%) (aOR: quartile 2, 1.40, 95% CI 1.19-1.61; quartile 3, 1.35, 95% CI 1.09-1.61; quartile 4, 1.47, 95% CI 1.20-1.74)., Conclusion: Neonates of nulliparous pregnant individuals living in U.S. neighborhoods with higher area deprivation were more likely to have abnormal birth weights at both extremes., Competing Interests: Financial Disclosure Judith Chung reports that money was paid to her institution from RTI. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To quantify the extent to which a standardized pain management order set reduced racial and ethnic inequities in post-cesarean pain evaluation and management., Methods: We conducted a retrospective cohort study to quantify racial and ethnic differences in pain evaluation and management before (July 2014-June 2016) and after implementation of a standardized post-cesarean order set (March 2017-February 2018). Electronic medical records were queried for pain scores >7/10, number of pain assessments, and opioid, nonsteroidal anti-inflammatory drug (NSAID), and acetaminophen doses. Outcomes were grouped into 0 to <24 and 24-48 h postpartum, and stratified by race/ethnicity (Hispanic, non-Hispanic Black [NHB], non-Hispanic White [NHW], Asian, and other), as documented in the electronic health record. Analyses included logistic regression for the categorical outcome of pain score >7 (severe pain), and linear regression, with propensity score adjustment. Main effect and interaction terms were used to calculate the difference-in-difference in pain process and outcome measures between the baseline and follow-up periods., Results: After order set implementation ( N =888), severe pain remained more common among NHB patients (% pain scores >7 NHW vs. NHB 0 to <24 h: 22% vs. 33%, p =0.003; 24-48 h: 26% vs. 40%, p <0.001). Among all patients, pain management processes changed after implementation of the order set, with overall fewer assessments, less Opioids, and more nonopioid analgesics. However, racial and ethnic inequities in a number of assessments and in treatment were unchanged (all p for interaction >0.05), with the exception of a modest increase in NSAID doses 24-48 h postpartum for Hispanic patients., Conclusion: A standardized pain management order set reduced overall postpartum opioid use, but did not reduce racial and ethnic disparities in pain evaluation and management. Future work should investigate racial equity-focused education and interventions designed to eliminate disparities in pain management., Competing Interests: The authors have no potential conflicts of interest., (© Celeste A. Green et al., 2023; Published by Mary Ann Liebert, Inc.)

We review research on gendered patterns of internalizing behaviors in adolescents and emerging adults during the COVID-19 pandemic. We find that young women reported worse mental health than young men. Transgender and gender-diverse (TGD) youth are underrepresented in mental health research but often report the highest internalizing disorders of any gender group. Finally, we use intersectionality as a lens to acknowledge how gender and other social identities (e.g., race, socioeconomic position) impact mental health. Overall, this review points to gender as a meaningful social construct that is relevant for understanding young people's internalizing symptoms during the pandemic. We call attention to the structural factors underlying gender disparities and the need for intersectionality-informed approaches to work towards mental health equity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Importance: Opioids administered to treat postsurgical pain are a major contributor to the opioid crisis, leading to chronic use in a considerable proportion of patients. Initiatives promoting opioid-free or opioid-sparing modalities of perioperative pain management have led to reduced opioid administration in the operating room, but this reduction could have unforeseen detrimental effects in terms of postoperative pain outcomes, as the relationship between intraoperative opioid usage and later opioid requirements is not well understood., Objective: To characterize the association between intraoperative opioid usage and postoperative pain and opioid requirements., Design, Setting, and Participants: This retrospective cohort study evaluated electronic health record data from a quaternary care academic medical center (Massachusetts General Hospital) for adult patients who underwent noncardiac surgery with general anesthesia from April 2016 to March 2020. Patients who underwent cesarean surgery, received regional anesthesia, received opioids other than fentanyl or hydromorphone, were admitted to the intensive care unit, or who died intraoperatively were excluded. Statistical models were fitted on the propensity weighted data set to characterize the effect of intraoperative opioid exposures on primary and secondary outcomes. Data were analyzed from December 2021 to October 2022., Exposures: Intraoperative fentanyl and intraoperative hydromorphone average effect site concentration estimated using pharmacokinetic/pharmacodynamic models., Main Outcomes and Measures: The primary study outcomes were the maximal pain score during the postanesthesia care unit (PACU) stay and the cumulative opioid dose, quantified in morphine milligram equivalents (MME), administered during the PACU stay. Medium- and long-term outcomes associated with pain and opioid dependence were also evaluated., Results: The study cohort included a total of 61 249 individuals undergoing surgery (mean [SD] age, 55.44 [17.08] years; 32 778 [53.5%] female). Increased intraoperative fentanyl and intraoperative hydromorphone were both associated with reduced maximum pain scores in the PACU. Both exposures were also associated with a reduced probability and reduced total dosage of opioid administration in the PACU. In particular, increased fentanyl administration was associated with lower frequency of uncontrolled pain; a decrease in new chronic pain diagnoses reported at 3 months; fewer opioid prescriptions at 30, 90, and 180 days; and decreased new persistent opioid use, without significant increases in adverse effects., Conclusions and Relevance: Contrary to prevailing trends, reduced opioid administration during surgery may have the unintended outcome of increasing postoperative pain and opioid consumption. Conversely, improvements in long-term outcomes might be achieved by optimizing opioid administration during surgery.

In this study, we investigated the dynamics of the ceca and litter microbiome of chickens from post-hatch through pre-harvest. To achieve this, six hundred one-day old Cobb 500 broiler chicks were raised on floor pens for 49 days in two separate houses. We performed short-read and full-length sequencing of the bacterial 16S rRNA gene present in the meconium and in cecal and litter samples collected over the duration of the study. In addition, we determined the antimicrobial resistance (AMR) phenotype of Escherichia coli and Enterococcus spp. isolated from the meconium and the ceca of 49-day old chickens. We monitored the relative humidity, temperature, and ammonia in each house daily and the pH and moisture of litter samples weekly. The overall microbial community structure of the ceca and litter consistently changed throughout the course of the grow-out and correlated with some of the environmental parameters measured ( p < 0.05). We found that the ceca and litter microbiome were similar in the two houses at the beginning of the experiment, but over time, the microbial community separated and differed between the houses. When we compared the environmental parameters in the two houses, we found no significant differences in the first half of the growth cycle (day 0-21), but morning temperature, morning humidity, and ammonia significantly differed ( p < 0.05) between the two houses from day 22-49. Lastly, the prevalence of AMR in cecal E. coli isolates differed from meconium isolates ( p < 0.001), while the AMR phenotype of cecal Enterococcus isolates differed between houses ( p < 0.05)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor BO declared a past collaboration with the author SA., (Copyright © 2023 Zwirzitz, Oladeinde, Johnson, Zock, Milfort, Fuller, Ghareeb, Foutz, Teran, Woyda, Abdo, Looft, Lawrence, Cudnik and Aggrey.)

Conceptions of adolescent "storm and stress" may be tied to a developmental mismatch that exists between young people's need for meaningful roles and autonomy - which we refer to as a need for enacting maturity - and the lack of such opportunities in most adolescents' contexts. First, we summarize our previous work on enacting maturity, including a review of the key components, links to wellbeing, and the nuances and limitations of this construct. Next, we extend this work by considering how the ecological contexts (e.g., family, school, community) young people are embedded in and their various intersecting social positions and identities (e.g., race/ethnicity, gender, immigrant origin) influence their experiences with enacting maturity. In this section, we pose several key questions for developmental scientists around: (a) identifying a young person's desire for, and phenomenological processing of, their adult-like roles, (b) understanding how complex and unequal responses to physical maturation shape opportunities for enacting maturity, and (c) attending to disparities in curricular and extracurricular pathways to leadership, responsibility, and autonomy. Finally, we discuss spaces with high potential to support enacting maturity, including both specially designed programs (e.g., youth participatory action research, leadership programs) as well as routine, everyday opportunities (e.g., interactions with teachers, training for companies that employ youth). We offer two levers for supporting enacting maturity across both types of spaces: adult allies and responsive organizations. Looking to exemplary programs, innovative leaders, social media, and case studies, we re-imagine how adults and organizations can promote young people enacting maturing in ways that are safe, worthwhile, and equitable., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past-authorship with the author PB., (Copyright © 2022 Ballard, Hoyt and Johnson.)

Postpartum pain is common, yet patient experiences and clinical management varies greatly. In the United States, pain-related expectations and principles of adequate pain management have been framed within established norms of Western clinical medicine and a biomedical understanding of disease processes. Unfortunately, this positioning of postpartum pain and the corresponding coping strategies and pain treatments is situated within cultural biases and systemic racism. This paper summarizes the history and existing literature that examines racial inequities in pain management to propose guiding themes and suggestions for innovation. This work is critical for advancing ethical practice and establishing more effective care for all patients., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: It has been reported that expression of OCT3 enhanced the sensitivity to melphalan in cells, indicative of potential roles of OCT3 in melphalan transport. Herein we investigated the association of select single nucleotide polymorphisms in SLC22A3 (gene encoding OCT3) with clinical outcomes in multiple myeloma (MM) patients with hematopoietic autologous stem cell transplants followed by high-dose melphalan therapy., Materials and Methods: Melphlan concentrations in blood samples from 108 MM patients were measured using liquid chromatography-tandem mass spectrometry (LC-MS/ΜS); genotypes of rs2048327, rs1810126, and rs3088442 in these patients were determined using quatitive RT-PCR assays., Results: Rs3088442 A variant-carriers had a significantly increased risk of severe oral mucositis in comparison with homozygous rs3088442 G-carriers with adjusted odds ratio of 4.00 (95% CI=1.25-14.7; p=0.027). Rs3088442 A carriers tended to have lower creatinine clearance (p=0.10) and higher maximum plasma concentration of melphalan (p=0.07)., Conclusion: OCT3 might be involved in melphalan transport in MM patients., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Breast cancer cells frequently disseminate to the bone marrow, where they either induce osteolysis or enter a dormant state. Downregulation of leukemia inhibitory factor receptor (LIFR), a known breast tumor suppressor, enables otherwise dormant MCF7 human breast cancer cells to become aggressively osteolytic. Hypoxia (low oxygen tensions), which may develop in tumors as a pathological response to the metabolic demands of the proliferating cells and as a physiological state in the bone, downregulates LIFR in breast cancer cells independent of hypoxia-inducible factor (HIF) signaling. However, the mechanism by which LIFR is repressed in hypoxia is unknown. Histone deacetylase (HDAC) inhibitors stimulate LIFR by increasing histone acetylation in the proximal promoter and induce a dormancy phenotype in breast cancer cells inoculated into the mammary fat pad. We therefore aimed to determine whether hypoxia alters histone acetylation in the LIFR promoter, and whether HDAC inhibitors effectively stimulate LIFR in breast cancer cells residing in hypoxic microenvironments. Herein, we confirmed that disseminated MCF7 cells became hypoxic in the bone and that hypoxia increased the epigenetic transcriptional repressor H3K9me3 in the distal LIFR promoter while H3K9ac, which promotes transcription, was significantly reduced. Furthermore, HDAC inhibitor treatment rescued hypoxic repression and dramatically increased expression of LIFR, p38β, and p21, which regulate tumor dormancy. In a second model of LIFR repression, in which parathyroid hormone-related protein (PTHrP) suppresses LIFR expression, we found that PTHrP binds to the distal LIFR promoter, and that PTHrP suppression of LIFR protein is similarly reversed by HDAC inhibitor treatment. Together, these data suggest that HDAC inhibitors stimulate LIFR regardless of the way it is repressed by the microenvironment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier GmbH.)

Background: Non-Hispanic black maternal race is a known risk factor for preterm birth. However, the contribution of paternal race is not as well established., Objective: We sought to evaluate the risk of preterm birth among non-Hispanic black, non-Hispanic white, and mixed non-Hispanic black and non-Hispanic white dyads., Study Design: This was a population-based cohort study of all live births in the United States from 2015 to 2017, using live birth records from the National Vital Statistics System. Singleton, nonanomalous infants whose live birth record included maternal and paternal self-reported race as either non-Hispanic white or non-Hispanic black were included. The primary outcome was preterm birth at <37 weeks' gestation; secondary outcomes included preterm birth at <34 and <28 weeks' gestation and delivery gestational age (as a continuous variable). Data were analyzed using chi-square, t test, analysis of variance, and logistic regression. A Kaplan-Meier survival curve was also generated., Results: There were 11,809,599 live births during the study period; 4,008,622 births met the inclusion criteria. Of included births, 291,647 (7.3%) occurred at <37 weeks' gestation. Using the convention of maternal race first followed by paternal race, preterm birth at <37 weeks' gestation was most common among non-Hispanic black and non-Hispanic black dyads (n=70,987 [10.8%]), followed by non-Hispanic black and non-Hispanic white (n=3137 [9.5%]), non-Hispanic white and non-Hispanic black (n=9136 [8.3%]), and non-Hispanic white and non-Hispanic white dyads (n=209,387 [6.5%]; P<.001 for trend). Births at <34 weeks' (n=74,474) and <28 weeks' gestation (n=18,474) were also more common among non-Hispanic black and non-Hispanic black dyads. Specifically, 24,351 (3.7%) non-Hispanic black and non-Hispanic black, 1017 (3.1%) non-Hispanic black and non-Hispanic white, 2408 (2.2%) non-Hispanic white and non-Hispanic black, and 46,698 non-Hispanic white and non-Hispanic white dyads delivered at <34 weeks' gestation, and 7988 non-Hispanic black and non-Hispanic black (1.2%), 313 (1.0%) non-Hispanic black and non-Hispanic white, 584 (0.5%) non-Hispanic white and non-Hispanic black, and 9589 (0.3%) non-Hispanic white and non-Hispanic white dyads delivered at <28 weeks' gestation. Non-Hispanic white and non-Hispanic white dyads delivered at a mean 38.8± standard deviation of 1.7 weeks' gestation, although non-Hispanic white and non-Hispanic black, non-Hispanic black and non-Hispanic white, and non-Hispanic black and non-Hispanic black dyads delivered at 38.6±2.0, 38.5±2.3, and 38.3±2.4 weeks' gestation, respectively (P<.001). Adjusted odds ratios for the association between maternal or paternal race and preterm birth were highest for non-Hispanic black and non-Hispanic black dyads at each gestational age cutoff: adjusted odds ratio, 1.60 (95% confidence interval, 1.11-1.19) (<37 weeks' gestation); adjusted odds ratio, 2.47 (95% confidence interval, 2.41-2.53) (<34 weeks' gestation); and adjusted odds ratio, 4.22 (95% confidence interval, 4.04-4.41) (<28 weeks' gestation) compared with the non-Hispanic white referent group. Models adjusted for insurance status, chronic hypertension, tobacco use during pregnancy, history of previous preterm birth, and male fetus. In the Kaplan-Meier survival analysis, non-Hispanic black and non-Hispanic black dyads delivered the earliest across the range of delivery gestational ages compared with all other combinations of dyads., Conclusion: Non-Hispanic black paternal race is a risk factor for preterm birth and should be considered when evaluating maternal a priori risk of prematurity. Future research should investigate the mechanisms behind this finding, including determining the contribution of factors, such as racism, maternal and paternal genetics, and epigenetics to an individual's risk of preterm birth., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Both acute and chronic stress can cause allostatic overload, or long-term imbalance in mediators of homeostasis, that results in disruptions in the maternal-placental-fetal endocrine and immune system responses. During pregnancy, disruptions in homeostasis may increase the likelihood of preterm birth and preeclampsia. Expectant mothers traditionally have high rates of anxiety and depressive disorders, and many are susceptible to a variety of stressors during pregnancy. These common life stressors include financial concerns and relationship challenges and may be exacerbated by the biological, social, and psychological changes occurring during pregnancy. In addition, external stressors such as major weather events (eg, hurricanes, tornados, floods) and other global phenomena (eg, the coronavirus disease 2019 pandemic) may contribute to stress during pregnancy. This review investigates recent literature published about the use of nonpharmacologic modalities for stress relief in pregnancy and examines the interplay between psychiatric diagnoses and stressors, with the purpose of evaluating the feasibility of implementing nonpharmacologic interventions as sole therapies or in conjunction with psychotherapy or psychiatric medication therapy. Further, the effectiveness of each nonpharmacologic therapy in reducing symptoms of maternal stress is reviewed. Mindfulness meditation and biofeedback have shown effectiveness in improving one's mental health, such as depressive symptoms and anxiety. Exercise, including yoga, may improve both depressive symptoms and birth outcomes. Expressive writing has successfully been applied postpartum and in response to pregnancy challenges. Although some of these nonpharmacologic interventions can be convenient and low cost, there is a trend toward inconsistent implementation of these modalities. Future investigations should focus on methods to increase ease of uptake, ensure each option is available at home, and provide a standardized way to evaluate whether combinations of different interventions may provide added benefit., (© 2020 Elsevier Inc. All rights reserved.)

Objectives: Despite persistent racial disparities in preterm birth (PTB) in the US among non-Hispanic (NH) black women compared to NH white women, it remains controversial whether sociodemographic factors can explain these differences. We sought to evaluate whether disparities in PTB persist among NH black women with high socioeconomic status (SES)., Study Design: We conducted a population-based cohort study of all live births in the US from 2015-2017 using birth certificate data from the National Vital Statistics System. We included singleton, non-anomalous live births among women who were of high SES (defined as having ≥ 16 years of education, private insurance, and not receiving Women, Infants and Children [WIC] benefits) and who identified as NH white, NH black, or 'mixed' NH black and white race. The primary outcome was PTB <37 weeks; secondary outcomes included PTB <34 and <28 weeks. In addition, analyses were repeated considering birthweight <2500g as a surrogate for preterm birth <37 weeks, birthweight <1500g as a surrogate for preterm birth <34 weeks, and birthweight <750g as a surrogate for preterm birth <28 weeks' gestation. Data were analyzed with chi-square, t-test, and logistic regression., Results: 2,170,686 live births met inclusion criteria, with 92.9% NH white, 6.7% NH black, and 0.4% both NH white and black race. Overall, 5.9% delivered <37, 1.3% <34, and 0.3 % <28 weeks. In unadjusted analyses of women with high SES, the PTB rate at each gestational age cutoff was higher for women of 'mixed' NH white and black race, and highest for women who were NH black only compared to women who were NH white only. In regression models we further adjusted for women with insurance and prenatal care their entire pregnancy, maternal race was associated with higher odds of PTB at each GA cutoff, with the highest odds observed at <28 weeks. Finally, in further adjustement analysis including only the 1,934,912 women who received prenatal care in the first trimester, findings were similar. Rates of preterm birth at each gestational age cutoff remained highest for women who identified as non-Hispanic black, intermediate for women identifying as both non-Hispanic black and white race, and lowest for non-Hispanic white women at <37 weeks (9.9% vs. 6.1% vs. 5.5%, respectively; p<0.001), <34 weeks (3.5% vs. 1.5% vs. 1.1%, respectively; p<0.001), and <28 weeks' gestation (1.2% vs. 0.4% vs. 0.2%, respectively, p<0.001)., Conclusions: Even among college-educated women with private insurance who are not receiving WIC, racial disparities in prematurity persist. These national findings are consistent with prior studies that suggest factors other than socio-demographics are important in the underlying pathogenesis of PTB., Competing Interests: The authors report no conflicts of interest or financial disclosures.

Objective: To evaluate whether the frequency of pain assessment and treatment differed by patient race and ethnicity for women after cesarean birth., Methods: We performed a retrospective cohort study of all women who underwent cesarean birth resulting in a liveborn neonate at a single institution between July 1, 2014, and June 30, 2016. Pain scores documented and medications administered after delivery were grouped into 0-24 and 25-48 hours postpartum time periods. Number of pain scores recorded, whether any pain score was 7 of 10 or greater, and analgesic medication administered were calculated. Models were adjusted for propensity scores incorporating maternal age, body mass index, gestational age, nulliparity, primary compared with repeat cesarean delivery, classical hysterotomy, and admission to the neonatal intensive care unit., Results: A total of 1,987 women were identified, and 1,701 met inclusion criteria. There were 30,984 pain scores documented. Severe pain (7/10 or greater) was more common among black (28%) and Hispanic (22%) women than among women who identified as white (20%) or Asian (15%). In the first 24 hours after cesarean birth, non-Hispanic white women had more documented pain assessments (adjusted mean 10.2) than, black, Asian, and Hispanic women (adjusted mean 8.4-9.5; P<.05). Results at 25-48 hours were similar, compared with non-Hispanic white women (adjusted mean 8.3). Black, Asian, and Hispanic women and women who were identified as other all received less narcotic medication at 0-24 hours postpartum (adjusted mean 5.1-7.5 oxycodone tablet equivalents; P<.001-.05), as well as at 25-28 hours postpartum., Conclusion: Racial and ethnic inequities in the experience, assessment and treatment of postpartum pain were identified. A limitation of our study is that we were unable to assess the role of patient beliefs about expression of pain, patient preferences with regards to pain medication, and beliefs and potential biases among health care providers.

Background/aim: SLC7A5 is recognized as the major mediator of melphalan uptake into multiple myeloma (MM) cells; however, its contribution to the inter-patient variability of melphalan efficacy and toxicity is yet to be well elucidated. This study aimed to investigate the impact of a single nucleotide polymorphism (SNP) rs4240803 in SLC7A5 on the gene expression, ex vivo sensitivity to melphalan, and clinical outcomes in MM patients who were undergoing autologous stem cell transplantation with high-dose melphalan., Materials and Methods: Peripheral blood mononuclear cells (PBMC) were collected from 108 MM patients prior to melphalan therapy. Clinical data were also collected from these patients following melphalan therapy., Results: rs4240803 was associated with elevated expression of SLC7A5 mRNA, higher ex vivo sensitivity to melphalan in PBMCs, and positive 90-day response in these patients (p=0.047, 0.10, 0.049, respectively)., Conclusion: rs4240803 impacted the expression of SLC7A5, thus contributing to the clinical response of MM patients to melphalan therapy., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Probuphine (buprenorphine) subdermal implants for the treatment of opioid-dependent patients.