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STEREOSELECTIVE COPOLYMERIZATION ENABLES DEGRADABLE, SEMICRYSTALLINE THERMOPLASTICS WITH POLYOLEFIN-LIKE PROPERTIES
Get PDFThermoplastics with excellent mechanical properties are broadly available and used ubiquitously. However, most end up in landfills or are downcycled. As a result, thermoplastics produced from sustainable materials and degradable into reusable materials are a desired commodity and their production is an active area of investigation. One approach to creating degradable thermoplastics is copolymerization: specifically, copolymerization between a monomer whose polymers usually provide the desired materials properties and a comonomer, which is capable of introducing degradable functionality into the copolymer (either innately or via its cross reaction with the first monomer). Herein, we report a novel stereoselective copolymerization between bio-derivable vinyl ethers and benzaldehydes that produces a stimuli-degradable analogue to isotactic poly(vinyl ether)s, isotactic poly(vinyl ether-co-benzaldehyde). This copolymer combines on-demand degradability with desirable material properties comparable to commercial poly(olefins). Master of Scienc
Gender, mental health symptoms, loss to clinic, and viral non-suppression 6 months after HIV care initiation among a cohort of people with HIV in Cameroon
Get PDFBackground People with HIV (PWH) experience high levels of mental health or substance use disorders (MSDs) which may compromise HIV treatment outcomes. Differences in the relationship between MSDs and HIV treatment outcomes by gender remain understudied. Methods We conducted interviews with 426 PWH aged ≥ 21 years initiating HIV care in Cameroon between June 2019 and March 2020. Clinic data and laboratory results were used to ascertain loss to clinic and viral non-suppression six months after HIV care initiation. We used log binomial regression models to assess the relationship between symptoms of depression (PHQ-9 scores > 9), anxiety (GAD-7 scores > 9), post-traumatic stress disorder (PTSD; PCL-5 scores > 30), and harmful alcohol use (AUDIT scores > 15) at HIV care initiation and 6-month loss to clinic and viral non-suppression in the study population overall, and among men and women, separately. Results Nearly 25% of individuals (N = 100) were lost to clinic at 6 months. Among the 326 individuals retained in care at their original clinic at 6 months, 234 had a measured viral load, of whom 28% were virally non-suppressed (N = 65). Among men, the risk of disengagement was greater among those who reported PTSD symptoms at care initiation compared to those who did not. Viral non-suppression was significantly higher among those reporting symptoms of anxiety at care initiation in the population retained overall and among men. Conclusions Men initiating HIV care with poor mental health may be particularly vulnerable to unstable care engagement and viral non-suppression. Interventions are needed for men specifically to foster improved mental health
Cooling down hotspots of retail tobacco products: addressing disparities in the built environment through policy
Get PDFMultiple disparities exist in the built environment for retail tobacco. Disproportionate concentrations of retail outlets result in variation in the availability of tobacco products, consumer access, and exposure to tobacco marketing. Neighborhoods with higher tobacco retail density have higher tobacco use than neighborhoods with lower density. Local policies focused on reducing tobacco retail concentration can address systematic disparities in the built environment. Using census-based synthetic populations for 30 US cities and retail tobacco location data, we simulated the disparity-reducing potential of three retail reduction policies: capping the number of available retail tobacco sales licenses, and minimum distance requirements between schools and retail locations and between retail locations themselves. Outcomes included retail concentration in density (stores/km2) and proximity for residents (km to nearest retail). We investigated differences across seven demographic and structural indicators in the tobacco retail environment including social, economic, and political dimensions. All the measures for retail concentration and demographic and structural context have considerable variation within and between cities. All three policies addressed disproportionate concentrations to varying degrees. The minimum distance requirements - 600m buffers around schools or retail locations - narrowed differences in the built environment for tobacco more so than halving the number of existing retail outlets through licensing caps. Policy effectiveness is context dependent. Buffer policies, for example, can be effective if retail locations are disproportionately concentrated near schools, near one another, or in low-income or racially/ethnically minoritized neighborhoods. Policy development should be informed not only by generalizable evidence but also by local data and familiarity with communities
Selective Mu-Opioid Receptor Imaging Using 18F‑Labeled Carfentanils
Get PDFCarfentanil, a highly potent synthetic opioid, paradoxically serves as a crucial positron emission tomography (PET) imaging tool in neurobiological studies of the mu-opioid receptor (MOR) system when labeled with carbon-11 ([11C]CFN). However, its clinical research use is hindered by extreme potency and the limited availability of short-lived carbon-11 (t 1/2 = 20.4 min). We present fluorine-18-labeled fluorocarfentanils ([18F]FCFNs), which can be produced at higher molar activity, allowing for lower mass doses and benefiting from the longer half-life of fluorine-18 (t 1/2 = 109.8 min), facilitating broader accessibility. Using copper-mediated radiofluorination, we synthesized a small [18F]FCFN library and conducted preclinical imaging evaluations. Two candidates, o- 18 F-1 and p-18F-2, showed optimal brain uptake, favorable pharmacokinetics, and high MOR-specific binding. Selectivity was confirmed through in vitro binding assays and in vivo PET scans. These [18F]FCFNs are promising for accessible human brain MOR imaging
Viral and Symptom Rebound Following Anti–Severe Acute Respiratory Syndrome Coronavirus 2 Monoclonal Antibody Therapy in a Randomized Placebo-Controlled Trial
Get PDFWe explored viral and symptom rebound after coronavirus disease 2019 amubarvimab-romlusevimab monoclonal antibody therapy versus placebo in the randomized ACTIV-2/A5401 trial. Participants underwent nasal severe acute respiratory syndrome coronavirus 2 polymerase chain reaction testing at study days 3, 7, 14, and 28. Viral rebound was defined as RNA ≥3 and ≥0.5 log10 copies/mL increase from day 3 or 7, and symptom rebound as hospitalization or any moderate/severe symptom for ≥2 days after initial symptom improvement. There was no difference in viral rebound (∼5%/arm) (analysis population n = 713) or symptom rebound among participants who initially improved (hazard ratio, 0.95 [95% confidence interval, .52–1.75]; analysis population n = 574); <1% had both viral/ symptom rebound
Virus-like particle vaccine with authentic quaternary epitopes protects against Zika virus-induced viremia and testicular damage.
Get PDFZika virus (ZIKV) caused unprecedented outbreaks in South America and the Caribbean in 2015-2016, leading primarily to a series of abnormalities in neonates termed congenital Zika syndrome. The threat of ZIKV reemergence has seen the development of multiple ZIKV vaccines that are at the preclinical stage or in early-stage clinical trials. Herein, we describe a pathway to the development of ZIKV vaccines generated using a baculovirus-insect cell expression system, which is widely applied for the manufacture of biologics for human use. Virus-like particle (VLP) vaccines comprising CprME and subviral particle (SVP) vaccines comprising prME were evaluated for their ability to mediate protection against ZIKV challenge in Ifnar1-/- mice. Initial attempts resulted in VLP and SVP vaccines that failed to present quaternary epitopes and did not provide effective protection. To improve the SVP vaccine, two modifications were introduced: firstly, an alanine to cysteine substitution (A264C) in the E domain II region to promote the formation of stabilized E homodimers and, secondly, the use of Spodoptera frugiperda Sf9 insect cells that had been adapted to grow and produce vaccine at a neutral pH of 7. E homodimers largely retain their pre-fusion conformation at pH 7, which is a requirement for the induction of effective neutralizing antibody responses. The stabilized SVP-A26C vaccine induced high levels of neutralizing antibodies and protected male Ifnar1-/- mice against viremia and testicular damage. Our study reiterates the need to present the immune system with E dimers arranged in authentic quaternary conformations and provides a scalable production method for this novel ZIKV vaccine.
IMPORTANCE We describe the generation of a subviral particle (SVP) vaccine comprising prME proteins of ZIKV, with an envelope protein substitution, A264C, that stabilizes E dimer formation. The SVP vaccine was produced in a novel Sf9 insect cell line adapted to grow in suspension at pH 7. The study highlights the importance of challenge experiments to ascertain whether the responses induced by an experimental vaccine actually mediate protection against virus infection and disease. The study also reiterates the contention that effective flavivirus vaccines need to present the immunogen in an authentic tertiary and quaternary structure with a pre-fusion conformation
The Role of Affect Regulation in Health Behavior Change
Get PDFOBJECTIVE: This research explores the relationship between affect regulation and health behavior change through two studies. Study 1 tested whether difficulties with affect regulation are associated with lower health-related behavioral intentions. Study 2 introduces the Calibrate and Qualify Model to examine the role of cognitive reappraisal in predicting health-related intentions and behavior. We posit that reappraisal could impact health behaviors either by shaping the favorability of health-related attitudes, norms, and perceived behavioral control, thereby increasing intentions and subsequently behavior (Calibrate Route) or by serving as a moderator, such that healthful cognitions better predict intentions and behavior at high levels of cognitive reappraisal (Qualify Route). METHOD: Study 1 was a cross-sectional study of 15 health behaviors (N = 319) that measured reasoned action approach (RAA) variables and difficulties in emotion regulation. Study 2 was a 3-month longitudinal study (N = 807) of eight health-related behaviors that tested the Calibrate and Qualify Model predictions using measures of cognitive reappraisal, RAA variables, and habit. RESULTS: Difficulties in emotion regulation, and limited access to affect regulation strategies in particular, predicted intentions to perform health behaviors (Study 1). Findings from Study 2 supported the Calibrate Route: cognitive reappraisal predicted intentions, and the reappraisal-intention relation was mediated by RAA variables. Supporting the Qualify Route, we observed a three-way interaction between habit, reappraisal, and intention, indicating that cognitive reappraisal combined with strong intentions attenuated the influence of habit on behavior. CONCLUSIONS: Our research suggests that affect regulation is an important consideration for predicting and understanding health behaviors.
Implementing motivational interviewing to improve endocrine therapy adherence among breast cancer patients: a qualitative process evaluation of the getset pilot intervention
Get PDFBackground This study evaluates the implementation of the GETSET (Guiding Endocrine Therapy Success through Empowerment and Teamwork) pilot, a motivational interviewing (MI) intervention aimed at improving endocrine therapy (ET) adherence among patients with breast cancer. Methods Using the Consolidated Framework for Implementation Research (CFIR), qualitative interviews were conducted with site staff (N = 2), patients (N = 4), and counselors (N = 2). Results The thematic analysis identified facilitators such as high-quality materials, ease of scheduling sessions, and effective communication among staff. However, barriers included lack of personalization and systemic issues like understaffing. Conclusions The study underscores the need to adapt implementation of behavioral interventions in a healthcare setting to improve ET adherence. As this was a process evaluation of a pilot study, future work should evaluate the barriers and facilitators to a larger clinical trial to identify if the same strategies should be refined
Disparities in Standard-of-Care, Advanced, and Same-Day Diagnostic Services among Patients with Abnormal Screening Mammography.
Get PDFBackground Diagnostic imaging and biopsy are used to evaluate abnormal screening mammography. Differences in on-site availability and receipt of these diagnostic services may contribute to disparities in breast cancer outcomes across sociodemographic groups. Purpose To identify multilevel factors associated with on-site availability and receipt of diagnostic imaging and biopsy after screening mammography. Materials and Methods This retrospective study included female patients (age range, 40-89 years) who underwent screening mammography at 136 facilities in the United States from January 2010 to December 2020. The primary exposure variables were race and ethnicity and neighborhood-level educational attainment, household income, and rurality. The adjustment variables were age, breast density, breast biopsy history, personal and family history of breast cancer, time from prior mammographic examination to screening mammography, screening modality, facility academic affiliation, and screening examination year. The relative risk (RR) of factors for on-site availability at screening facilities and undergoing standard-of-care imaging (ie, mammography and/or US) and advanced diagnostic imaging (ie, digital breast tomosynthesis, MRI) and biopsy, and undergoing any same-day diagnostic service and biopsy were estimated using modified Poisson regression. Results In total, 1 123 177 female patients (median age, 59 years; IQR, 51-67 years) underwent 3 519 502 screening mammographic examinations: 10.3% Asian patients (362 440 of 3 519 502), 12.7% Black patients (447 777 of 3 519 502), 6.5% Hispanic patients (227 177 of 3 519 502), 68.3% White patients (2 403 159 of 3 519 502), and 2.2% all other races and ethnicities (78 949 of 3 519 502). In most fully adjusted models, race or ethnicity and neighborhood-level socioeconomic status were not associated with on-site diagnostic service availability. However, compared with White patients, patients belonging to racial and ethnic minority groups were less likely to undergo same-day diagnostic services after abnormal screening mammography (Asian patients: RR, 0.74 [95% CI: 0.64, 0.85]; Black patients: RR, 0.56 [95% CI: 0.49, 0.63]; Hispanic patients: RR, 0.61 [95% CI: 0.52, 0.71]). Black patients were less likely to undergo same-day biopsies after an abnormal diagnostic workup (RR, 0.46; 95% CI: 0.33, 0.65). Conclusion Although no evidence existed that on-site diagnostic service availability varied by race and ethnicity in most models, patients in racial and ethnic minority groups were less likely to be provided same-day diagnostic services and Black patients were less likely to undergo same-day biopsy. © RSNA, 2025 Supplemental material is available for this article. See also the editorial by Mullen in this issue
A world less safe and secure
Get PDFOn 20 January, President Trump announced the withdrawal of the United States from the World Health Organization (WHO). President Trump shares many of the same concerns about WHO as previous administrations, including improved transparency, financial oversight, and accountability. He also believes that China has exerted undue influence on WHO—a charge that WHO adamantly denies. But the US cannot influence WHO if it is not at the table. WHO will remain at the center of global health governance, but this withdrawal will limit US leadership to protect public health and challenge WHO coordination in facing global challenges