ABSTRACT Introduction To evaluate the efficacy and safety of sotatercept, an activin signaling inhibitor, in pulmonary arterial hypertension (PAH). Methods We searched PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) comparing sotatercept versus placebo in PAH. We calculated pooled risk ratios (RR) and mean differences (MD) with their 95% confidence intervals (CI) using a random-effects model. Heterogeneity was assessed with I2 statistics. The GRADE approach was used to assess the certainty of evidence. Results Three RCTs comprising 601 patients were included. Compared to placebo, sotatercept significantly improved 6-minute walk distance (MD 40.57 m; 95% CI 26.64 to 54.5; p < 0.01), and WHO functional class (RR 2.04; 95% CI 1.53 to 2.7; p < 0.01). Sotatercept reduced pulmonary vascular resistance (MD −233.18 dyn·sec·cm−5; 95% CI −295.84 to −170.52; p < 0.01) and pulmonary artery pressure (MD −14.94 mmHg; 95% CI −19.62 to −10.27; p < 0.01) at study end. No significant differences were observed in all-cause mortality or NT-proBNP levels. Sotatercept was associated with epistaxis, increased hemoglobin, and telangiectasia adverse events. Conclusions Sotatercept improves exercise capacity, WHO functional class and pulmonary hemodynamics in PAH, with an acceptable safety profile. Long-term studies are needed to confirm sustained benefits. Protocol registration www.crd.york.ac.uk/prospero identifier is CRD420251032174.

ABSTRACT Therapeutic potential of cannabinoids and terpenes in cannabis products is complicated by the possibility to alleviate pain yet exacerbate anxiety symptoms. Little is known about how cannabis practices, and preferences for cannabinoids and terpenes differ among medical cannabis patients who use cannabis to relieve pain, or anxiety, or both. A concurrent explanatory mixed-methods design was utilized. The quantitative analytical sample (n = 1,060) consisted of participants who self-reported past 90-day cannabis use to relieve: physical pain only (14.8%), feeling uptight/anxious only (29.5%), or both conditions (55.7%). We examined between-group differences in demographic variables, cannabis practices and preferences. Qualitative interviews with a subsample of patients (n = 39) were analyzed thematically regarding cannabinoid/terpene preferences to contextualize quantitative results. Compared to the Anxiety-only group, pain groups were more likely to use high potency flower/extract products (i.e., moon rocks/caviar), topicals/creams and CBD; the Pain/anxiety group was more likely to use Rick Simpson Oil and look for CBD, CBN, CBG and CBC. Both quantitative and qualitative data supported preferences for CBD and caryophyllene for pain relief, myrcene for pain and anxiety relief, while Anxiety-only group was less likely to prefer terpinolene. Future studies need to assess if cannabis practices and preferences are associated with symptom improvements over time.

ABSTRACT Though effective evidence-based treatments for child and adolescent eating disorders exist, there are significant barriers for families looking to access this care. One potential solution is the development of interventions, such as Family-Based Treatment for Primary Care (FBT-PC), that can be delivered in more accessible settings by primary care providers. FBT-PC has been evaluated in one health system in the Midwest United States and found to have a large effect on patient outcomes and comparable rates of retention and hospitalization to gold-standard FBT. To have maximum reach, however, FBT-PC needs to be adaptable for a wide range of primary care settings with different patient populations and clinical needs. We describe the adaptation of FBT-PC for a unique healthcare setting, including adjustments to context, content, and training. Findings suggest that the adapted intervention is acceptable to providers for use with a diverse patient population.

Aspirin-exacerbated respiratory disease (AERD) is characterized by asthma, chronic rhinosinusitis with polyps, and sensitivity to aspirin (ASA). Optimal treatment requires coordinated medical and surgical management, with prior studies showing that a single-center approach to AERD management yields improved sinonasal patient outcomes. Here, we sought to evaluate whether institutional experience enhances pulmonary and sinonasal outcomes in patients with AERD undergoing functional endoscopic sinus surgery (FESS) followed by ASA desensitization (AD). Single-center, retrospective cohort study evaluating patients undergoing FESS and AD from 2016 to 2024. Cohorts were defined as "early" (2016-2019) and "late" (2020-2024). Demographics, clinical history, and quality of life metrics [eg, 22-Item SinoNasal Outcome Test (SNOT-22) score] were assessed. Cohorts were compared with statistical significance defined as P < .05. Two hundred sixty-two patients (n = 145 early, 117 late) met inclusion criteria. The late cohort was younger (mean 49.6 vs 56.4 years, P = .042) with fewer prior surgeries (1.33 vs 2.64, P ≤ .001) at the time of referral. Results showed a reduced need for inhaled corticosteroids and beta-agonists in the late cohort and improved SNOT-22 rhinologic sub-scores in the early post-treatment period (post-FESS, pre-AD; 2-3 months post-treatment; 4-6 months post-treatment), with a reduced need for revision surgery (0% vs 6.9%, P = .010). Greater institutional experience in AERD management yields significantly improved pulmonary outcomes and more rapid improvement in sinonasal outcomes. This was felt to be due to enhanced communication and coordination of care between the allergist and rhinologist, with implications for healthcare expenditures.

The objective of this study is to examine the associations among asthma, depression, and anxiety with sleep outcomes among youth in Puerto Rico and determine whether age moderates the associations. Data came from surveys of 333 youth aged 10-17 living in Puerto Rico. Predicted probabilities derived from logistic regression models were used to assess the associations of asthma, depression, and anxiety with sleep outcomes. Models included interactions between age group (10-13 vs 14-17) and asthma, depression, and anxiety when predicting sleep outcomes. The predicted probability of obtaining a sufficient amount of sleep was 15.9 percentage-points higher among those with asthma compared to those without asthma (p = 0.009), 21.9 percentage-points higher among older youth with asthma compared to older youth without asthma (p = 0.004), and 33.9 percentage-points lower among younger youth with depression compared to younger youth without depression (p = 0.019). There were no significant differences in the predicted probabilities of perceived sleep quality according to asthma, depression, or anxiety status. Findings suggest that age moderates the associations among asthma, depression, and sleep among youth in Puerto Rico. Younger youth with depression may be at increased risk for poor sleep outcomes.

Intrinsically disordered and artificially denatured foldable proteins have many properties in common, even though the distribution of amino acid residues generally differ. Both are traditionally described as either adopting molten globule or random coil-like structure, depending on their amino acid composition. For a long period of time, it was believed that with the exception of glycine and proline, conformational preferences of individual amino acid residues are very similar, and therefore, not of great concern. This article discusses experimental and bioinformatical data which show that individual Ramachandran plot distributions in unfolded proteins depend on the characteristics of side chains. Furthermore, ample experimental evidence suggests the presence of nearest neighbor interactions between residues which are ignored in the classical random coil model. The article reviews and discusses work that emphasizes the necessity of a thorough understanding of the local behavior of disordered and unfolded proteins alike for an understanding of the coiled state of proteins. Unresolved issues are delineated and research perspectives suggested.

BackgroundFew studies have characterised community food environments and their influence on dietary behaviours in Latin America. In particular, community food environment data do not exist for Chilean contexts. This study aims to characterise the community food environment across neighbourhoods in three major Chilean cities and explore associations between these food environments and fruit and vegetable consumption among adult residents.MethodsWe used a geospatial query tool to identify, georeference, and classify food establishments (FE, n = 46,950) across 3 large Chilean cities (Santiago, Valparaíso, Concepción). Neighbourhood characteristics were derived from the 2017 Census (n = 2,442 neighbourhoods) while individual-level data came from the 2017 National Health Survey (Encuesta Nacional de Salud, n = 1,275 adults). Lower dietary quality was proxied by non-daily consumption of fruits or vegetables (ND-FV, prevalence 17.3%). We used random intercept logistic regression models adjusting for survey participants age, gender, educational attainment, neighbourhood population density and social environment.ResultsThe median density of FE was 41.36 per km2, increasing with neighbourhood population density and more favourable social environments. Ready-for-consumption FE and small food retail were the most prevalent types (68% and 11%, respectively). The adjusted odds of ND-FV consumption was approximately 20% higher with increases in the z-score of those FE types. No associations were found between other types of FE and ND-FV consumption.ConclusionFood establishments were unequally distributed across urban Chilean neighbourhoods. Overall, unhealthy outlets are predominant. Higher densities of small and ready-to-consume FE were associated with lower fruit and vegetable consumption. These findings underscore the need for targeted public policies aimed at promoting healthier food environments, reducing social inequalities in food access within Chilean cities, and improving dietary quality.

Integrated primary care (IPC) can improve access to behavioral health (BH) care, reduce stigma, and facilitate early intervention. However, few studies have examined key informants' perceptions of IPC engagement. We qualitatively identified convergent and divergent perspectives of care team members and caregivers on pediatric IPC-related engagement barriers, facilitators, and suggestions for improvements. Care team members (N = 48, 98.3% female, 72.9% non-Hispanic/Latine White) and caregivers (N = 10, 100% female, 10.0%. Asian, 30.0% Black/African American, 60.0% non-Hispanic/Latine White) completed semistructured interviews on IPC engagement in a large pediatric primary care network. Thematic analysis was used to iteratively identify patterns of meaning, as well as convergent and divergent themes across informant groups. Convergent barriers included stigma, prolonged wait times, limited BH knowledge, difficulty navigating services, and limited BH provider availability. Whereas care team members identified more family-related barriers (e.g., beliefs, experiences), caregivers identified divergent barriers such as limited childcare. Perceived engagement facilitators converged across groups and mostly pertained to systems-related factors such as the colocation of services. Converging recommendations included additional behavioral clinicians and support staff, provision of psychoeducational resources, and expanding IPC services. Although key informant groups similarly perceived many IPC benefits, including increased BH access, there are continued patient/family barriers to IPC engagement, with divergence in care team members' versus caregivers' views about the nature of these barriers. Findings suggest a need for systems-level changes to address these barriers and highlight the importance of including the unique perspectives of care team members and caregivers in future research examining IPC effectiveness. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

MICB is a ligand for NKG2D. We have shown NK cells are central to lung transplant acute lung injury (ALI) via NKG2D activation, and increased MICB in bronchoalveolar lavage predicts ALI severity. Separately, we found a MICB polymorphism (MICBG406A) is associated with decreased ALI risk. We hypothesized this polymorphism would protect against severe SARS-CoV-2 respiratory disease. We analyzed 1,036 patients hospitalized with SARS-CoV-2 infection from the IMPACC cohort. Associations between MICBG406A and outcomes were determined by linear regression or Cox Proportional Hazards models. We also measured immune profiles of peripheral blood, upper and lower airway. We identified 560 major allele homozygous patients, and 426 and 50 with one or two copies of the variant allele. MICBG406A conferred reduced odds of severe COVID-19 (OR = 0.73, CI = 0.58-0.93, P = 0.04). MICBG406A homozygous participants demonstrated 34% reduced cumulative odds for mechanical ventilation or death (CI = 0.51-0.85, P = 0.005) and 43% reduced risk for mortality (CI = 0.35-0.77, P = 0.001). Patients with MICBG406A variant alleles had reduced soluble inflammatory mediators and differential regulation of multiple immune pathways. These findings demonstrate a novel association between increasing MICBG406A variant allele copies and reduced COVID-19 severity, independent of SARS-CoV-2 viral burden and humoral immunity, suggesting the NKG2D-ligand pathway as an intervention target.

ABSTRACTThe combined antegrade and retrograde endoscopic rendezvous technique effectively restores patency for esophageal short-segment obstructing strictures (<3 cm). However, long-segment strictures typically require complex surgery, with endoscopic management rarely reported. We report a 44-year-old man with a 9 cm esophageal obstruction due to peptic stricture who was at high risk of esophageal resection due to severe cardiac disease and prior abdominal surgeries. He underwent successful recanalization using a rendezvous technique. Serial dilations with subsequent esophageal stenting restored luminal patency. This case highlights the feasibility of an endoscopic approach as a safe and effective alternative to surgery in long-segment peptic strictures.