SchoolHEAT: Racial and Ethnic Inequity in School Temperature.

Exposure to high environmental temperature is detrimental to health through multiple pathways. This paper describes disparities in school-based high-temperature exposure at metropolitan schools in the United States. Using school location and sociodemographic data from the National Center for Education Statistics, neighborhood data from the US Census Bureau, and land surface temperature (LST) data from the Aqua Earth-observing satellite mission, we find that for every 10% more Black or Hispanic residents in the neighborhood, schools have LST 0.25 °C and 0.38 °C hotter, respectively. When the Black or Hispanic student population is greater than the neighborhood population, LST is an additional 0.20 °C and 0.40 °C for each 10% increase in students over neighborhood population, respectively. Black and Hispanic students are overrepresented in the hottest schools, making up 58.7% of students in the hottest 20% of schools, compared to only 30.0% of students in the coolest 20% of schools.

Development of the ADFICE_IT clinical decision support system to assist deprescribing of fall-risk increasing drugs: A user-centered design approach.

INTRODUCTION: Deprescribing fall-risk increasing drugs (FRIDs) is promising for reducing the risk of falling in older adults. Applying appropriate deprescribing in practice can be difficult due to the outcome uncertainties associated with stopping FRIDs. The ADFICE_IT intervention addresses this complexity with a clinical decision support system (CDSS) that facilitates optimum deprescribing of FRIDs by using a fall-risk prediction model, aggregation of deprescribing guidelines, and joint medication management. METHODS: The development process of the CDSS is described in this paper. Development followed a user-centered design approach in which users and experts were involved throughout each phase. In phase I, a prototype of the CDSS was developed which involved a literature and systematic review, European survey (n = 581), and semi-structured interviews with clinicians (n = 19), as well as the aggregation and testing of deprescribing guidelines and the development of the fall-risk prediction model. In phase II, the feasibility of the CDSS was tested by means of two usability testing rounds with users (n = 11). RESULTS: The final CDSS consists of five web pages. A connection between the Electronic Health Record allows for the retrieval of patient data into the CDSS. Key design requirements for the CDSS include easy-to-use features for fast-paced clinical environments, actionable deprescribing recommendations, information transparency, and visualization of the patient's fall-risk estimation. Key elements for the software include a modular architecture, open source, and good security. CONCLUSION: The ADFICE_IT CDSS supports physicians in deprescribing FRIDs optimally to prevent falls in older patients. Due to continuous user and expert involvement, each new feedback round led to an improved version of the system. Currently, a cluster-randomized controlled trial with process evaluation at hospitals in the Netherlands is being conducted to test the effect of the CDSS on falls. The trial is registered with ClinicalTrials.gov (date; 7-7-2022, identifier: NCT05449470).

BRCA genetic testing and counseling in breast cancer: how do we meet our patients' needs?

BRCA1 and BRCA2 are tumor suppressor genes that have been linked to inherited susceptibility of breast cancer. Germline BRCA1/2 pathogenic or likely pathogenic variants (gBRCAm) are clinically relevant for treatment selection in breast cancer because they confer sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. BRCA1/2 mutation status may also impact decisions on other systemic therapies, risk-reducing measures, and choice of surgery. Consequently, demand for gBRCAm testing has increased. Several barriers to genetic testing exist, including limited access to testing facilities, trained counselors, and psychosocial support, as well as the financial burden of testing. Here, we describe current implications of gBRCAm testing for patients with breast cancer, summarize current approaches to gBRCAm testing, provide potential solutions to support wider adoption of mainstreaming testing practices, and consider future directions of testing.

County-level Racial/Ethnic Residential Segregation and Physical Activity Behavior among US Adults.

The relationship between racial/ethnic residential segregation and physical activity (PA) remains unclear with both positive and negative associations between segregation and PA recently reported. We aimed to examine the relationship between county-level residential segregation and total daily PA and domain-specific PA and whether these associations varied by gender. Participants (N = 2625, mean age [SD] = 45.2 [15.4]) were recruited from the AmeriSpeak panel who completed up to two Activities Completed over Time in 24 Hours (ACT24) previous day recalls in 2019. PA outcomes were created for the following: (1) light PA (LPA), (2) moderate-to-vigorous PA (MVPA), (3) total active time, and (4) domain-specific PA, including leisure, work, household, transport, personal, and other activities. County-level residential segregation based on isolation. Weighted generalized linear models were used to examine the relationship between county-level segregation and each PA outcome, controlling for age, gender, race/ethnicity, income, employment, body mass index, county-level poverty, and census region. Overall, results showed no association between county-level residential segregation and LPA, MVPA, total active time, and domain-specific PA among NH Black and Hispanic populations. Among NH Black females, greater residential segregation was associated with more total hours/day of activity (ß = 3.54, 95% CI [0.23, 6.85]). Only NH Black females living in segregated neighborhoods had more total active time. Additionally, it is important to acknowledge that these relationships may vary among NH Black and Hispanic populations. Future studies should examine the interaction between segregation and a broader range of individual, contextual, and environmental factors in relation to PA and domain-specific PA.

Validation studies and multi-omics analysis of Zhx2 as a candidate quantitative trait gene underlying brain oxycodone metabolite (oxymorphone) levels and behavior.

Sensitivity to the subjective reinforcing properties of opioids has a genetic component and can predict addiction liability of opioid compounds. We previously identified Zhx2 as a candidate gene underlying increased brain concentration of the oxycodone (OXY) metabolite oxymorphone (OMOR) in BALB/cJ (J) versus BALB/cByJ (By) females that could increase OXY state-dependent reward. A large structural intronic variant is associated with a robust reduction of Zhx2 expression in J mice, which we hypothesized enhances OMOR levels and OXY addiction-like behaviors. We tested this hypothesis by restoring the Zhx2 loss-of-function in Js (MVKO) and modeling the loss-of-function variant through knocking out the Zhx2 coding exon (E3KO) in Bys and assessing brain OXY metabolite levels and behavior. Consistent with our hypothesis, Zhx2 E3KO females showed an increase in brain OMOR levels and OXY-induced locomotor activity. However, contrary to our hypothesis, state-dependent expression of OXY-CPP was decreased in E3KO females and increased in E3KO males. We also overexpressed Zhx2 in the livers and brains of Js and observed Zhx2 overexpression in select brain regions that was associated with reduced OXY state-dependent learning. Integrative transcriptomic and proteomic analysis of E3KO mice identified astrocyte function, cell adhesion, extracellular matrix properties, and endothelial cell functions as pathways influencing brain OXY metabolite concentration and behavior. These results support Zhx2 as a quantitative trait gene underlying brain OMOR concentration that is associated with changes in OXY behavior and implicate potential quantitative trait mechanisms that together inform our overall understanding of Zhx2 in brain function.

Pharmacy barriers for transgender and gender diverse young adults.

BACKGROUND: Transgender and gender diverse (TGD) individuals face substantial physical and mental health care barriers. Community pharmacies are one of the most accessible healthcare settings; however, concern for discrimination at the pharmacy has been reported. It is important to gain a better understanding of TGD individual's perspectives and experiences at the pharmacy to ensure optimal and inclusive care. OBJECTIVE: To identify TGD individual experiences and barriers at the pharmacy. METHODS: This IRB-approved qualitative study recruited TGD young adults in the United States between ages 18-29 years old for semi-structured focus group discussions. Questions focused on barriers to obtaining medications at the pharmacy and negative or positive experiences with pharmacists. Interviews were recorded, transcribed, and transcripts were analyzed for common themes amongst participants. RESULTS: Nine 1.5-2-hour focus groups were conducted and included 30 participants (2-6 participants in each group). All participants reported having been prescribed medications by a physician or mental health provider. Participants self-reported issues at pharmacies and with pharmacy personnel. Major themes included issues accessing medications and supplies (needles, syringes), questioning of prescription validity and patient identity, and lack of education or understanding of TGD individuals by pharmacy staff. CONCLUSION: TGD individuals experience barriers at the pharmacy and concerning issues with pharmacy staff. Education, structural competency, and improvements in gender-related data management are necessary for pharmacists and pharmacy staff to provide equitable and inclusive care for TGD individuals.

"Curing of common plasmids in gram-negative bacteria using a Cas9-based conjugative vector".

We report the creation of 17 Escherichia coli strains harboring the conjugative plasmid pLCasCureT with a CRISPR-Cas9 system to surgically "cure" the most common plasmids among Enterobacterales species. This approach can create isogenic pairs of strains to study host-plasmid interactions, correlate plasmid genotype and phenotype, and create plasmid-free cloning strains.

Biopsychosocial pathways model of early childhood appetite self-regulation: Temperament as a key to modulation of interactions among systems.

The widespread discrimination against individuals with obesity often stems from a simplistic perception of obesity as a mere consequence of personal choices of overeating and insufficient physical activity. This reductionist perception fails to acknowledge the complexity of the epidemic of obesity, which extends beyond diet and exercise decisions. The concept of appetite self-regulation (ASR) has been explored as a crucial element in identifying obesogenic behavioral approaches to food. Although an extensive understanding of ASR in children is essential as an early precursor and modifiable factor influencing obesity, the prevailing view of self-regulation of eating solely as a matter of cognitive and behavioral processing tends to overlook interacting systems of influences. This narrow approach attributes obesity to the lack of voluntary self-control in food consumption while neglecting to account for the biological, psychological, and social influences implicated in the developmental processes of ASR, which may further contribute to the stigmatization of obesity. The current critical analysis provides a comprehensive developmental framework that could guide future studies with testable hypotheses, outlining pathways of interactions among biopsychosocial systems, all of which contribute to the development of ASR in early childhood. Adopting developmental perspectives allows a holistic approach to investigating ASR, which accounts for intricate interactions between biological (B), psychological (P), and social (S) factors influential in the early manifestation of ASR.

Effect of an Inflatable Colon on Colorectal Cancer Knowledge and Screening Intent Among Male Attendees at State Fairs in Two Midwestern States, 2023.

Introduction: Colorectal cancer (CRC) is the third most-diagnosed cancer among men and women in the US. This study aimed to evaluate the influence of an interactive inflatable colon exhibit on CRC knowledge and screening intent among men attending state fairs in 2 midwestern states. Methods: At the 2023 state fairs in 2 midwestern states, eligible participants (men aged 18-75 y who could speak and read English and resided in 1 of the 2 states) completed a presurvey, an unguided tour of the inflatable Super Colon, and a postsurvey. Primary outcomes were changes in knowledge (actual and perceived) and CRC screening intent from presurvey to postsurvey. We used χ2 tests to examine differences in survey results between the 2 sites and the association between demographic characteristics and behaviors (knowledge and intentions) before entering the Super Colon exhibit. We used the McNemar test to examine differences in presurvey to postsurvey distributions. Results: The study sample (N = 940) comprised 572 men at site A (60.8%) and 368 men at site B (39.2%). Except for 1 question, baseline CRC knowledge was relatively high. Greater perceived knowledge was inversely associated with greater actual knowledge. After touring the Super Colon, participants improved their actual knowledge of CRC prevention and self-perceived CRC knowledge. Most participants (95.4%) agreed that the Super Colon was effective for teaching people about CRC. Conclusion: These findings emphasize the role of community-based educational initiatives in encouraging CRC screening uptake and increasing research participation among men and affirm that the inflatable colon is as an effective educational tool for increasing CRC knowledge and encouraging early-detection screening behavior among men.

Exposure to organophosphate ester flame retardants and plasticizers and associations with preeclampsia and blood pressure in pregnancy.

BACKGROUND: Organophosphate esters (OPEs), flame retardants and plasticizers found widely in consumer products, may impact vascularization processes in pregnancy. Yet, the association between maternal exposure to OPEs and both preeclampsia and blood pressure during pregnancy remains understudied. METHODS: Within the LIFECODES Fetal Growth Study (N = 900), we quantified 8 OPE metabolites from maternal urine collected at up to 3 time points during pregnancy and created within-subject geometric means. Outcomes included diagnosis of preeclampsia and longitudinal systolic (SBP) and diastolic (DBP) blood pressure measurements (mean = 14 per participant). Cox proportional hazards models were used to estimate associations between OPE metabolites and preeclampsia. Associations between average OPE metabolite concentrations and repeated blood pressure measurements were estimated using generalized estimating equations. RESULTS: Five OPE metabolites were detected in at least 60% of samples; 3 metabolites detected less frequently (5-39%) were examined in an exploratory analysis as ever vs. never detectable in pregnancy. There were 46 cases of preeclampsia in our study population. Associations between OPE metabolites and preeclampsia were null. We noted several divergent associations between OPE metabolites and longitudinal blood pressure measurements. An interquartile range (IQR) difference in average bis(2-chloroethyl) phosphate concentrations was associated with a decrease in SBP (-0.81 mmHg, 95% confidence interval [CI]: -1.62, 0.00), and, conversely, bis(1-chloro-2-propyl) phosphate was associated with a slight increase in SBP (0.94 mmHg, 95% CI: 0.28, 1.61). We also noted a decrease in SBP in association with several metabolites with low detection frequency. CONCLUSIONS: We observed null associations between OPE metabolites and preeclampsia, but some positive and some inverse associations with blood pressure in pregnancy. While our study was well-designed to assess associations with blood pressure, future studies with a larger number of preeclampsia cases may be better poised to investigate the association between OPE metabolites and phenotypes of this heterogenous hypertensive disorder of pregnancy.

Patterns of Care and Outcomes of Patients with Small Gastrointestinal Stromal Tumors at a High-Volume Sarcoma Center.

BACKGROUND: The course of subclinical gastrointestinal stromal tumors (GISTs) is variable. The management of small GISTs is not well-defined. METHODS: Records of patients presenting with small GISTs with documented follow-up appointment at our institution between 2016 and 2022 were identified and reviewed. Comparative univariate analysis to compare patient and tumor characteristics and outcomes was performed. RESULTS: Eighty-six patients were followed for a median of 3.7 years (range 0.1-20 years). The median size at presentation was 1.7 (range 0.1-2.5) cm. A total of 51.2% (n = 44) underwent surgery before or immediately after initial presentation for pain (18.2%), bleeding (15.9%), or patient preference (6.8%). Another 17.4% (n = 15) had delayed surgery for tumor growth (40%), patient preference (2.7%), bleeding (6.7%), or pain (6.7%). The remaining 31.4% (n = 27) of patients never underwent surgery for reasons that included no growth/stability (44.4%), concomitant cancer diagnosis/treatment (29.6%), comorbidities (14.8%), and patient preference (3.7%). Patients who underwent surveillance without intervention compared with those who had delayed surgery were older (71.1 vs. 60.8 years, p < 0.001) with multiple comorbidities or a concurrent cancer diagnosis (70.3% vs. 20%, p = 0.005). There were no differences in survival or rate of distant metastases. Average time to surgery in the delayed group was 2 (range 0.1-10.3) years, and 86% of these patients underwent surgery by 5.5 years after diagnosis. CONCLUSIONS: In older patients with comorbidities or concurrent cancer diagnoses, opting out of surgery does not affect survival. Conversely, younger patients, free from significant comorbidities or other diagnoses, may consider surgery or active surveillance for up to 5 years, with comparable outcomes.

#CRCandMe: results of a pre-post quasi-experimental study of a mass media campaign to increase early-onset colorectal cancer awareness in Utah and Wisconsin.

Overall colorectal cancer (CRC) incidence and mortality have been decreasing for several decades; however, since the early 1990s CRC incidence rates have nearly doubled among adults aged under 50 years. This study pilot-tested a community-based mass-media campaign aimed at improving knowledge and awareness of early-onset CRC in this population. The campaign (#CRCandMe) was deployed from June to September 2023 in Utah and Wisconsin. To evaluate its success (reach) and inform future campaigns, key performance indicators were defined (e.g., impressions, website traffic). To evaluate change in knowledge in the target population, the knowledge and awareness of participants recruited via consumer panels was assessed at baseline (n=235) and follow-up (n=161). The number of correct answers for each of seven knowledge items was calculated at baseline (pre-intervention) and follow-up (post-intervention). McNemar's test was employed to assess significant differences in the seven knowledge items between the two timepoints. The campaign delivered over 26.7 million impressions and nearly 43,000 clicks. A 15-second video ad received 221,985 plays, with 57,270 users watching to completion. Pre-survey results revealed that while 74% of participants were able to correctly identify CRC signs, only 18% could identify risk factors. Knowledge scores slightly improved from baseline to follow-up, with statistically significance for the question related to CRC signs (P=0.0004). This study demonstrated wide reach and may inform future larger-scale interventions and public health initiatives aimed at reducing CRC incidence and improving health outcomes for at-risk adults aged under 50 years.

The ultrasonic vocalization (USV) syllable profile during neonatal opioid withdrawal and a kappa opioid receptor component to increased USV emissions in female mice.

RATIONALE: Opioid use during pregnancy can lead to negative infant health outcomes, including neonatal opioid withdrawal syndrome (NOWS). NOWS comprises gastrointestinal, autonomic nervous system, and neurological dysfunction that manifest during spontaneous withdrawal. Variability in NOWS severity necessitates a more individualized treatment approach. Ultrasonic vocalizations (USVs) in neonatal mice are emitted in isolation as a stress response and are increased during opioid withdrawal, thus modeling a negative affective state that can be utilized to test new treatments. OBJECTIVES: We sought to identify the behavioral and USV profile, brainstem transcriptomic adaptations, and role of kappa opioid receptors in USVs during neonatal opioid withdrawal. METHODS: We employed a third trimester-approximate opioid exposure model, where neonatal inbred FVB/NJ pups were injected twice-daily with morphine (10mg/kg, s.c.) or saline (0.9%, 20 ul/g, s.c.) from postnatal day(P) 1 to P14. This protocol induces reduced weight gain, hypothermia, thermal hyperalgesia, and increased USVs during spontaneous morphine withdrawal. RESULTS: On P14, there were increased USV emissions and altered USV syllables during withdrawal, including an increase in Complex 3 syllables in FVB/NJ females (but not males). Brainstem bulk mRNA sequencing revealed an upregulation of the kappa opioid receptor (Oprk1), which contributes to withdrawal-induced dysphoria. The kappa opioid receptor (KOR) antagonist, nor-BNI (30 mg/kg, s.c.), significantly reduced USVs in FVB/NJ females, but not males during spontaneous morphine withdrawal. Furthermore, the KOR agonist, U50,488h (0.625 mg/kg, s.c.), was sufficient to increase USVs on P10 (both sexes) and P14 (females only) in FVB/NJ mice. CONCLUSIONS: We identified an elevated USV syllable, Complex 3, and a female-specific recruitment of the dynorphin/KOR system in increased USVs associated with neonatal opioid withdrawal severity.