Primary care perspectives on prescribing anti-obesity medication for adolescents.

BACKGROUND: Recent pediatric guidelines recommend clinicians offer anti-obesity medication (AOM) as an adjunct to intensive lifestyle intervention. OBJECTIVE: To investigate pediatricians' perspectives about prescribing AOM, including barriers and facilitators. METHODS: An investigator-developed survey was emailed to primary care pediatric physicians (n = 187) and advanced practice providers (n = 190) within an academic-affiliated network. The survey evaluated how willing clinicians were to prescribe AOM and their agreement with 25 statements about barriers and facilitators. Three vignettes explored AOM decision-making. Multinomial logistic regression was used to determine relative risk ratios for willingness to prescribe by agreement with each statement. RESULTS: Among 74 respondents (20% response rate), 24% were willing, 42% uncertain and 34% unwilling to prescribe. Most (64%) agreed that AOM should be managed only by specialists. Willingness to prescribe was associated with clinician motivation and belief in guideline practicality and applicability. Unwillingness was associated with beliefs that patients would not continue AOM long enough for benefit and that there was insufficient time or resources to implement. In vignettes, 52% were willing to prescribe AOM for a patient with severe obesity and metabolic complications, versus 11% for a patient with obesity and possible disordered eating. CONCLUSIONS: Willingness to prescribe AOM was low and was associated with perceived practicality and appropriateness for patients.

Mechanics of spindle orientation in human mitotic cells is determined by pulling forces on astral microtubules and clustering of cortical dynein.

The forces that orient the spindle in human cells remain poorly understood due to a lack of direct mechanical measurements in mammalian systems. We use magnetic tweezers to measure the force on human mitotic spindles. Combining the spindle's measured resistance to rotation, the speed at which it rotates after laser ablating astral microtubules, and estimates of the number of ablated microtubules reveals that each microtubule contacting the cell cortex is subject to ∼5 pN of pulling force, suggesting that each is pulled on by an individual dynein motor. We find that the concentration of dynein at the cell cortex and extent of dynein clustering are key determinants of the spindle's resistance to rotation, with little contribution from cytoplasmic viscosity, which we explain using a biophysically based mathematical model. This work reveals how pulling forces on astral microtubules determine the mechanics of spindle orientation and demonstrates the central role of cortical dynein clustering.

Prediabetes Prevalence by Adverse Social Determinants of Health in Adolescents.

Importance: Several clinical practice guidelines advise race- and ethnicity-based screening for youth-onset type 2 diabetes (T2D) due to a higher prevalence among American Indian and Alaska Native, Asian, Black, and Hispanic youths compared with White youths. However, rather than a biological risk, this disparity likely reflects the inequitable distribution of adverse social determinants of health (SDOH), a product of interpersonal and structural racism. Objective: To evaluate prediabetes prevalence by presence or absence of adverse SDOH in adolescents eligible for T2D screening based on weight status. Design, Setting, and Participants: This cross-sectional study and analysis used data from the 2011 to 2018 cycles of the National Health and Nutrition Examination Survey. Data were analyzed from June 1, 2023, to April 5, 2024. Participants included youths aged 12 to 18 years with body mass index (BMI) at or above the 85th percentile without known diabetes. Main Outcomes and Measures: The main outcome consisted of an elevated hemoglobin A1c (HbA1c) level greater than or equal to 5.7% (prediabetes or undiagnosed presumed T2D). Independent variables included race, ethnicity, and adverse SDOH (food insecurity, nonprivate health insurance, and household income <130% of federal poverty level). Survey-weighted logistic regression was used to adjust for confounders of age, sex, and BMI z score and to determine adjusted marginal prediabetes prevalence by race, ethnicity, and adverse SDOH. Results: The sample included 1563 individuals representing 10 178 400 US youths aged 12 to 18 years (mean age, 15.5 [95% CI, 15.3-15.6] years; 50.5% [95% CI, 47.1%-53.9%] female; Asian, 3.0% [95% CI, 2.2%-3.9%]; Black, 14.9% [95% CI, 11.6%-19.1%]; Mexican American, 18.8% [95% CI, 15.4%-22.9%]; Other Hispanic, 8.1% [95% CI, 6.5%-10.1%]; White, 49.1% [95% CI, 43.2%-55.0%]; and >1 or other race, 6.1% [95% CI, 4.6%-8.0%]). Food insecurity (4.1% [95% CI, 0.7%-7.5%]), public insurance (5.3% [95% CI, 1.6%-9.1%]), and low income (5.7% [95% CI, 3.0%-8.3%]) were each independently associated with higher prediabetes prevalence after adjustment for race, ethnicity, and BMI z score. While Asian, Black, and Hispanic youths had higher prediabetes prevalence overall, increasing number of adverse SDOH was associated with higher prevalence among White youths (8.3% [95% CI, 4.9%-11.8%] for 3 vs 0.6% [95% CI, -0.7% to 2.0%] for 0 adverse SDOH). Conclusions and Relevance: Adverse SDOH were associated with higher prediabetes prevalence, across and within racial and ethnic categories. Consideration of adverse SDOH may offer a more actionable alternative to race- and ethnicity-based screening to evaluate T2D risk in youth.

Pitfalls in the Detection of Volatiles Associated with Heated Tobacco and e-Vapor Products When Using PTR-TOF-MS.

We investigated the applicability of proton transfer reaction-time-of-flight mass spectrometry (PTR-TOF-MS) for quantitative analysis of mixtures comprising glycerin, acetol, glycidol, acetaldehyde, acetone, and propylene glycol. While PTR-TOF-MS offers real-time simultaneous determination, the method selectivity is limited when analyzing compounds with identical elemental compositions or when labile compounds present in the mixture produce fragments that generate overlapping ions with other matrix components. In this study, we observed significant fragmentation of glycerin, acetol, glycidol, and propylene glycol during protonation via hydronium ions (H3O+). Nevertheless, specific ions generated by glycerin (m/z 93.055) and propylene glycol (m/z 77.060) enabled their selective detection. To thoroughly investigate the selectivity of the method, various mixtures containing both isotope-labeled and unlabeled compounds were utilized. The experimental findings demonstrated that when samples contained high levels of glycerin, it was not feasible to perform time-resolved analysis in H3O+ mode for acetaldehyde, acetol, and glycidol. To overcome the observed selectivity limitations associated with the H3O+ reagent ions, alternative ionization modes were investigated. The ammonium ion mode proved appropriate for analyzing propylene glycol (m/z 94.086) and acetone (m/z 76.076) mixtures. Concerning the nitric oxide mode, specific m/z were identified for acetaldehyde (m/z 43.018), acetone (m/z 88.039), glycidol (m/z 73.028), and propylene glycol (m/z 75.044). It was concluded that considering the presence of multiple product ions and the potential influence of other compounds, it is crucial to conduct a thorough selectivity assessment when employing PTR-TOF-MS as the sole method for analyzing compounds in complex matrices of unknown composition.

Easy and Effective Method for α-CD:N2O Host-Guest Complex Formation.

α-CD:N2O "host-guest" type complexes were formed by a simple solid-gas reaction (N2O sorption into α-CD) under different gas pressures and temperatures. The new N2O inclusion method applied in the present study was compared with the already known technique based on the crystallization of clathrates from a water solution of α-CD saturated with N2O. A maximum storage capacity of 4.5 wt.% N2O was achieved when charging the cyclodextrin from a gas phase. The amount of included gas decreases to 1.3 wt.% when the complex is stored in air at 1 atm and room temperature, analogous to that achieved by the crystallization of α-CD:N2O. Furthermore, it was shown that the external coordination of N2O to either the upper or lower rim of α-CD without hydration water displacement is the preferred mode of binding, due to hydrogen bonds with neighboring -OH groups from the host macrocycle and three of the hydration water molecules nearby. The capacity of α-CD to store N2O and the thermal stability of the α-CD:N2O complex demonstrated promising applications of these types of complexes in food and beverages.

Associations Among Plurisexual Identity, Intimate Partner Violence, Reproductive Coercion, and Parental Monitoring in a Sample of Adolescent and Young Adult Pregnant People.

Purpose: The goal of this study was to examine plurisexual identity, intimate partner violence (IPV), reproductive coercion, and parental monitoring among pregnant 13-21-year-olds. Methods: We conducted a cross-sectional analysis of data collected from a cohort of pregnant adolescents and young adults between October 2019 and May 2023 (n = 398). Logistic regression was completed to assess IPV and reproductive coercion as a function of plurisexual identity. Next, we assessed potential interactions between parental monitoring and plurisexual identity and examined IPV and reproductive coercion as a function of parental monitoring for the full sample and stratified by plurisexuality. Results: Plurisexual identity was associated with IPV (adjusted odds ratio [aOR] = 2.3; confidence interval [CI]: 1.4-4.0). IPV was inversely related to parental monitoring among plurisexual participants (aOR: 0.51; CI: 0.32-0.82), but this association was not significant for heterosexual participants (aOR: 1.1; CI: 0.75-1.6). Conclusions: This work demonstrates the importance of parental monitoring in supporting young plurisexual pregnant people.

"How Fluent Do I Need to Be to Say I'm Fluent?" Research Experiences of Communities that Speak Languages Other than English.

OBJECTIVE: The goal of this study was to partner with community organizations to understand the research experiences of communities who speak languages other than English (LOE). METHODS: We conducted semi-structured qualitative interviews in Spanish, Nepali, Mandarin, French, or Kizigua with LOE community members and community leaders who completed recruitment and data collection. Audio-recordings of the interviews were transcribed and translated. We conducted qualitative coding using a mixed deductive-inductive analysis approach and thematic analyses using three rounds of affinity clustering. This study occurred in partnership with an established community-academic collaboration. RESULTS: Thirty community members and six community leaders were interviewed. 83% of LOE participants were born outside of the US and most participants (63%) had never participated in a prior research study. Six themes emerged from this work. Many participants did not understand the concept of research, but those that did thought that inclusion of LOE communities is critical for equity. Even when research was understood as a concept, it was often inaccessible to LOE individuals, particularly because of the lack of language services. When LOE participants engaged in research, they did not always understand their participation. Participants thought that improving research trust was essential and recommended partnering with community organizations and disseminating research results to the community. CONCLUSION: This study's results can serve as an important foundation for researchers seeking to include LOE communities in future research to be more inclusive and scientifically rigorous.

Applying a Language Justice Framework in Research: A Step Toward Achieving Health Equity.

People who use languages other than English (LOE) are rarely included in research in the United States. LOE communities face numerous health disparities that are rooted in language injustice and other intersecting oppressions including racism and xenophobia. Equitable inclusion of LOE communities in research is an important step to disrupt health disparities. We propose a new conceptual framework on language justice in research to support researchers in conducting equitable multilingual research. This language justice in research framework comprises six core pillars of best practices required for achieving language justice during all the stages of the research process including conceptualization, budgeting, data collection and analysis, and dissemination. We also present key definitions, examples of how core pillars can be applied, and structural solutions to achieving language justice. The application of the language justice in research framework is designed: (a) to achieve health equity, data equity, and antiracism across the research continuum and (b) to disrupt health disparities in systems and institutions that are disproportionately impacting LOE communities.

Projected impact of anti-obesity pharmacotherapy use on racial and ethnic disparities in adolescent obesity.

BACKGROUND: Paediatric obesity disproportionately impacts individuals from minoritized racial and ethnic backgrounds. Recent guidelines support use of anti-obesity pharmacotherapy for adolescents with obesity, but the potential impact on disparities in obesity prevalence has not been evaluated. OBJECTIVES: To model changes in obesity prevalence with increasing utilization of anti-obesity pharmacotherapy among adolescents. METHODS: Data representative of American adolescents ages 12-17 years were obtained from the National Health and Nutrition Examination Survey, cycles 2011 through pre-pandemic 2020. A body mass index (BMI) reduction of 16.7% was applied to each participant based on clinical trial results of weekly subcutaneous semaglutide 2.4 mg among adolescents. Utilization disparities were based on utilization of the same medication class among adults. Obesity prevalence was calculated assuming utilization of 10%-100%, stratified by race and ethnicity. RESULTS: Among 4442 adolescents representing 26 247 384 American adolescents, projected overall obesity prevalence decreased from 22.2% to 8.4% with 100% utilization. However, disparities increased relative to Non-Hispanic White youth, with prevalence among Non-Hispanic Black and Mexican American youth ranging from 40%-60% higher to 90%-120% higher, respectively. CONCLUSIONS: Increasing utilization of anti-obesity pharmacotherapy may widen relative disparities in obesity, particularly if utilization is unequal. Advocacy for equitable access is needed to minimize worsening of obesity-related disparities.

Features of Changes in the Structure and Properties of a Porous Polymer Material with Antibacterial Activity during Biodegradation in an In Vitro Model.

Hybrid porous polymers based on poly-EGDMA and polylactide containing vancomycin, the concentration of which in the polymer varied by two orders of magnitude, were synthesized. The processes of polymer biodegradation and vancomycin release were studied in the following model media: phosphate-buffered saline (PBS), trypsin-Versene solution, and trypsin-PBS solution. The maximum antibiotic release was recorded during the first 3 h of extraction. The duration of antibiotic escape from the polymer samples in trypsin-containing media varied from 3 to 22 days, depending on the antibiotic content of the polymer. Keeping samples of the hybrid polymer in trypsin-containing model media resulted in acidification of the solutions-after 45 days, up to a pH of 1.84 in the trypsin-Versene solution and up to pH 1.65 in the trypsin-PBS solution. Here, the time dependences of the vancomycin release from the polymer into the medium and the decrease in pH of the medium correlated. These data are also consistent with the results of a study of the dynamics of sample weight loss during extraction in the examined model media. However, while the polymer porosity increased from ~53 to ~60% the pore size changed insignificantly, over only 10 µm. The polymer samples were characterized by their antibacterial activity against Staphylococcus aureus, and this activity persisted for up to 21 days during biodegradation of the material, regardless of the medium type used in model. Surface-dependent human cells (dermal fibroblasts) adhere well, spread out, and maintain high viability on samples of the functionalized hybrid polymer, thus demonstrating its biocompatibility in vitro.

Mass spectrometry-detected MGUS is associated with obesity and other novel modifiable risk factors in a high-risk population.

ABSTRACT: Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition of multiple myeloma with few known risk factors. The emergence of mass spectrometry (MS) for the detection of MGUS has provided new opportunities to evaluate its risk factors. In total, 2628 individuals at elevated risk for multiple myeloma were enrolled in a screening study and completed an exposure survey (PROMISE trial). Participant samples were screened by MS, and monoclonal proteins (M-proteins) with concentrations of ≥0.2 g/L were categorized as MS-MGUS. Multivariable logistic models evaluated associations between exposures and MS outcomes. Compared with normal weight (body mass index [BMI] of 18.5 to <25 kg/m2), obesity (BMI of ≥30 kg/m2) was associated with MS-MGUS, adjusting for age, sex, Black race, education, and income (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.21-2.47; P = .003). High physical activity (≥73.5 metabolic equivalent of task (MET)-hours per week vs <10.5 MET-hours per week) had a decreased likelihood of MS-MGUS (OR, 0.45, 95% CI, 0.24-0.80; P = .009), whereas heavy smoking and short sleep had increased likelihood of MS-MGUS (>30 pack-years vs never smoker: OR, 2.19; 95% CI, 1.24-3.74; P = .005, and sleep <6 vs ≥6 hours per day: OR, 2.11; 95% CI, 1.26-3.42; P = .003). In the analysis of all MS-detected monoclonal gammopathies, which are inclusive of M-proteins with concentrations of <0.2 g/L, elevated BMI and smoking were associated with all MS-positive cases. Findings suggest MS-detected monoclonal gammopathies are associated with a broader range of modifiable risk factors than what has been previously identified. This trial was registered at www.clinicaltrials.gov as #NCT03689595.

Economic Abuse and Help-Seeking Intentions Among Adolescents.

Economic adolescent relationship abuse (ARA) includes coercive behaviors leading to interference with education, employment, and finances. To date, no study has examined help seeking among adolescents and young adults if they were to experience economic ARA. The goals of this article include examining: (a) help-seeking intentions of adolescents regarding economic ARA; (b) help-seeking sources and reasons for not seeking help; and (c) differences in help-seeking intentions based on age, race/ethnicity, gender identity, and experiences of economic ARA. We conducted a cross-sectional survey of adolescents ages 13-19 focused on economic ARA experiences and help seeking. We performed descriptive statistics of help-seeking intentions, sources, and barriers. We utilized logistic regression, adjusted for age, race/ethnicity, and gender identity, to explore associations between economic ARA victimization and help-seeking intentions. Of 2,852 participants, 56% said they would seek help for economic ARA. Adolescents with positive help-seeking intentions shared that they would seek help from their parents (43%) or friends (35%). Those less likely to seek help were concerned about others finding out (32%), not being believed (31%), or authority figures being notified (31%). Help-seeking intentions were lower among Black/African American adolescents (aOR = 0.55, CI [0.43, 0.70]) and Multiracial adolescents (aOR = 0.26, CI [0.16, 0.42]) compared to White adolescents. Help-seeking intentions were higher among gender diverse adolescents (aOR = 5.78, CI [2.98, 11.22]) and those ages 15-17 years (aOR = 1.84, CI [1.36, 2.47]) compared to those identifying as female and ages 18-19 years. Help-seeking intentions were lower among adolescents who experienced economic ARA (aOR = 0.61, CI [0.51, 0.72]). While the majority of adolescents reported that they would seek help if they experienced economic ARA, those who had experienced economic ARA were less likely to report intentions to seek help. Supportive interventions for adolescents experiencing economic ARA are needed.

Direct conversion of amino acids to oxetanol bioisosteres via photoredox catalysis.

Carboxylic acids are an important structural feature in many drugs, but are associated with a number of unfavorable pharmacological properties. To address this problem, carboxylic acids can be replaced with bioisosteric mimics that interact similarly with biological targets but avoid these liabilities. Recently, 3-oxetanols have been identified as useful carboxylic acid bioisosteres that maintain similar hydrogen-bonding capacity while decreasing acidity and increasing lipophilicity. However, the installation of 3-oxetanols generally requires multistep de novo synthesis, presenting an obstacle to investigation of these promising bioisosteres. Herein, we report a new synthetic approach involving direct conversion of carboxylic acids to 3-oxetanols using a photoredox-catalyzed decarboxylative addition to 3-oxetanone. Two versions of the transformation have been developed, in the presence or absence of CrCl3 and TMSCl cocatalysts. The reactions are effective for a variety of N-aryl α-amino acids and have excellent functional group tolerance. The Cr-free conditions generally provide higher yields and avoid the use of chromium reagents. Further, the Cr-free conditions were extended to a series of N,N-dialkyl α-amino acid substrates. Mechanistic studies suggest that the Cr-mediated reaction proceeds predominantly via in situ formation of an alkyl-Cr intermediate while the Cr-free reaction proceeds largely via radical addition to a Brønsted acid-activated ketone. Chain propagation processes provide quantum yields of 5 and 10, respectively.

Supporting Intimate Partner Violence Survivors and Their Children in Pediatric Healthcare Settings.

Intimate partner violence (IPV) is a pervasive public health epidemic that influences child health and thriving. In this article, we discuss how pediatric healthcare providers and systems can create healing-centered spaces to support IPV survivors and their children. We review the use of universal education and resource provision to share information about IPV during all clinical encounters as a healing-centered alternative to screening. We also review how to support survivors who may share experiences of IPV, focused on validation, affirmation, and connection to resources. Clinicians are provided key action items to implement in their clinical settings.

Clustering of cortical dynein regulates the mechanics of spindle orientation in human mitotic cells.

The forces which orient the spindle in human cells remain poorly understood due to a lack of direct mechanical measurements in mammalian systems. We use magnetic tweezers to measure the force on human mitotic spindles. Combining the spindle's measured resistance to rotation, the speed it rotates after laser ablating astral microtubules, and estimates of the number of ablated microtubules reveals that each microtubule contacting the cell cortex is subject to ~1 pN of pulling force, suggesting that each is pulled on by an individual dynein motor. We find that the concentration of dynein at the cell cortex and extent of dynein clustering are key determinants of the spindle's resistance to rotation, with little contribution from cytoplasmic viscosity, which we explain using a biophysically based mathematical model. This work reveals how pulling forces on astral microtubules determine the mechanics of spindle orientation and demonstrates the central role of cortical dynein clustering.

Interactions with alloparents are associated with the diversity of infant skin and fecal bacterial communities in Chicago, United States.

INTRODUCTION: Social interactions shape the infant microbiome by providing opportunities for caregivers to spread bacteria through physical contact. With most research focused on the impact of maternal-infant contact on the infant gut microbiome, it is unclear how alloparents (i.e., caregivers other than the parents) influence the bacterial communities of infant body sites that are frequently contacted during bouts of caregiving, including the skin. METHODS: To begin to understand how allocare may influence the diversity of the infant microbiome, detailed questionnaire data on infant-alloparent relationships and specific allocare behaviors were coupled with skin and fecal microbiome samples (four body sites) from 48 infants living in Chicago, United States. RESULTS: Data from 16S rRNA gene amplicon sequencing indicated that infant skin and fecal bacterial diversity showed strong associations (positive and negative) to having female adult alloparents. Alloparental feeding and co-sleeping displayed stronger associations to infant bacterial diversity compared to playing or holding. The associations with allocare behaviors differed in magnitude and direction across infant body sites. Bacterial relative abundances varied by infant-alloparent relationship and breastfeeding status. CONCLUSION: This study provides some of the first evidence of an association between allocare and infant skin and fecal bacterial diversity. The results suggest that infants' exposure to bacteria from the social environment may vary based on infant-alloparent relationships and allocare behaviors. Since the microbiome influences immune system development, variation in allocare that impacts the diversity of infant bacterial communities may be an underexplored dimension of the social determinants of health in early life.