Core Mental Health Clinician Capacity and Use Rates in the US Military.

Importance: Active duty service members have higher mental health stress and cannot choose where to live. It is imperative to understand how geographic access may be associated with their ability to obtain mental health treatment and how the COVID-19 pandemic was associated with these patterns. Objective: To identify changes in the prevalence and intensity of mental health care use when service members experienced changes in core mental health clinician (defined to include psychiatrists, psychiatric nurse practitioners, clinical psychologists and social workers, and marriage and family therapists) capacity in their communities and whether patterns changed from before to after the onset of the COVID-19 pandemic. Design, Setting, and Participants: This retrospective cohort study of the active duty population between January 1, 2016, and December 31, 2022, was conducted using individual fixed-effects models to estimate changes in the probability of mental health care visits and visit volume when a person moved across communities with adequate core mental health clinician capacity (≥1 clinician/6000 beneficiaries), shortage areas (<1 clinician/6000 beneficiaries), and areas with 0 clinicians within a 30-minute drive time. All US active duty service members stationed in the continental US, Hawaii, and Alaska were included. Data were analyzed from January through July 2024. Main Outcomes and Measures: The first set of outcomes captured the probability of making at least 1 mental health care visit in a given quarter; the second set of outcomes captured the intensity of visits (ie, the number of visits log transformed). Results: This study included 33 039 840 quarterly observations representing 2 461 911 unique active duty service members from the Army, Navy, Marines, and Air Force (1 959 110 observations among Asian or Pacific Islander [5.9%], 5 309 276 observations among Black [16.1%], 5 287 168 observations among Hispanic [16.0%], and 18 739 827 observations among White [56.7%] individuals; 27 473 563 observations among males [83.2%]; mean [SD] age, 28.20 [7.78] years). When an active duty service member moved from a community with adequate capacity at military treatment facilities to one with 0 clinicians within a 30-minute drive, the probability of a mental health visit to any clinician decreased by 1.13 percentage points (95% CI, -1.21 to -1.05 percentage points; equivalent to a 11.6% relative decrease) and the intensity of total visits was reduced by 7.7% (95% CI, -9.0% to -6.5%). The gap increased from before to after the onset of the COVID-19 pandemic, from 8.5% (equivalent to -0.82 percentage points [95% CI, -0.92 to -0.73 percentage points]) to 16.2% (equivalent to -1.58 percentage points [95% CI, -1.70 to -1.46 percentage points]) in the probability of visiting any clinician type for mental health. Conclusions and Relevance: In this study, active duty personnel assigned to locations without core military mental health clinicians within a 30-minute drive time were less likely to obtain mental health care and had fewer mental health care visits than those in communities with adequate military mental health capacity even if there was adequate coverage from the civilian sector. The care disparity increased after the onset of the COVID-19 pandemic.

Geographic Access to High-Volume Mechanical Thrombectomy Centers in Florida, 2019.

Background and Objectives: Mechanical thrombectomy (MT) improves outcomes for acute ischemic stroke (AIS) due to large vessel occlusion, but is time sensitive and requires specialized infrastructure. Professional organizations and certification bodies have promulgated minimum procedural volume standards for centers and for individual proceduralists but it is unclear whether enforcing these requirements would decrease geographic access to MT. Therefore, we sought to evaluate the potential impact of applying a minimum procedural volume threshold on geographic access to MT. Methods: We identified all hospital discharges for stroke where an MT procedure was performed at any nonfederal hospital in Florida in 2019 using statewide hospital discharge data. We then generated geographic service area maps based on prespecified ground transport distances for the subset of hospitals that performed at least 1 MT and for those that performed at least 15 MTs that year, the minimum volume threshold required for thrombectomy capable and comprehensive stroke centers by the Joint Commission. Then, using zip code centroids and patient-level discharge hospital data, we computed the proportion of patients with AIS who lived within each of the generated service areas. Results: A total of 105 of 297 hospitals performed MT; of those, 51 (17%) were low-volume centers (1-14 MTs/year) and 54 (18%) were high-volume centers (≥15 MTs/year). High-volume centers accounted for nearly 95% of all MTs performed in the state. Most patients hospitalized with AIS (87%) lived within 20 miles (or an estimated as a 1-hour driving time) of a hospital that performed at least 1 MT, and all (100%) lived within 115 miles (or estimated as 3-hour driving time). Setting a minimum MT volume threshold of 15 would decrease the proportion of stroke patients living within 1-hour driving time of an MT center from 87% to 77%. Discussion: In 2019, most Florida stroke patients lived within a 1-hour ground transport time to a center that performed at least 1 MT and all lived within 3-hour driving time of an MT center, irrespective of whether a minimum procedural volume threshold of 15 cases per year was applied or not.

Reduced mortality with antimicrobial stewardship guided by BioFire FilmArray Blood Culture Identification 2 panel in critically ill patients with bloodstream infection: A retrospective propensity score-matched study.

OBJECTIVES: To investigate whether using the BioFire® FilmArray® Blood Culture Identification 2 panel (BCID2) leads to timely antimicrobial therapy and improves patient outcomes in critically ill patients with bloodstream infections (BSIs). METHODS: This retrospective observational study included patients with BSIs admitted to the intensive care unit from July 1, 2021, to August 31, 2023. Patients were divided into groups receiving appropriate or inappropriate antimicrobial therapy. Those receiving inappropriate therapy underwent adjustments using standard-of-care (SOC) testing or BCID2. Propensity score matching (PSM) was performed on the original cohort (Model 1) and a time-window bias-adjusted cohort (Model 2). Clinical impact of BCID2-guided antimicrobial adjustment was analysed in both models. RESULTS: A total of 181 patients received inappropriate antimicrobial therapy, with 33 undergoing BCID2 testing and 148 undergoing SOC testing. Following PSM and time-window bias adjustment, 66 patients were analysed in Model 1 and 46 patients in Model 2. BCID2 significantly reduced the median time to appropriate antimicrobial therapy (40.8 vs. 74.0 h in Model 1; 42.8 vs. 68.9 h in Model 2) and the day-28 mortality rate (27.8% vs. 77.1%, P < 0.001 in Model 1; 23.5% vs. 58.6%, P = 0.021 in Model 2). In multivariate regression analysis, BCID2-guided antimicrobial adjustment was an independent prognostic factor for day-28 mortality (adjusted odds ratio [aOR] 0.07 in Model 1 and aOR 0.12 in Model 2). CONCLUSION: BCID2-guided antimicrobial stewardship was associated with a shorter time to appropriate antimicrobial therapy and reduced day-28 mortality in critically ill patients with BSIs receiving inappropriate antimicrobial therapy.

Development and Validation of a Comprehensive Analysis of the Competing Endogenous circRNA/miRNA/mRNA Network for the Identification of Immune-Related Targets in Esophageal Squamous Cell Carcinoma.

Immunotherapy for esophageal squamous cell carcinoma (ESCC) exhibits notable variability in efficacy. Concurrently, recent research emphasizes circRNAs' impact on the ESCC tumor microenvironment. To further explore the relationship, we leveraged circRNA, microRNA, and mRNA sequence datasets to construct a comprehensive immune-related circRNA-microRNA-mRNA network, revealing competing endogenous RNA (ceRNA) roles in ESCC. The network comprises 16 circular RNAs, 13 microRNAs, and 1,560 mRNAs. Weighted gene co-expression analysis identified immune-related modules, notably cancer-associated fibroblast (CAF) and myeloid-derived suppressor cell modules, correlating significantly with immune and stemness scores. Among them, the CAF module plays a crucial role in extracellular matrix function and effectively discriminates ESCC patients. Four hub collagen family genes within CAF correlated robustly with CAF, macrophage infiltration, and T-cell exclusion. In-house sequencing and RT-qPCR validated their elevated expression. We also identified CAF module-targeting drugs as potential ESCC treatments. In summary, we established an immune-related circRNA-miRNA-mRNA network that not only illuminates ceRNA functionality but also highlights circRNAs' involvement in the CAF through collagen gene targeting. These findings hold promise to predict ESCC immune landscapes and therapy responses, ultimately aiding in more personalized and effective clinical decision-making.

Investigation of the Octahedral Network Structure in Formamidinium Lead Bromide Nanocrystals by Low-Dose Scanning Transmission Electron Microscopy.

Metal halide perovskites (MHP) are highly promising semiconductors. In this study, we focus on FAPbBr3 nanocrystals, which are of great interest for green light-emitting diodes. Structural parameters significantly impact the properties of MHPs and are linked to phase instability, which hampers long-term applications. Clearly, there is a need for local and precise characterization techniques at the atomic scale, such as transmission electron microscopy. Because of the high electron beam sensitivity of MHPs, these investigations are extremely challenging. Here, we applied a low-dose method based on four-dimensional scanning transmission electron microscopy. We quantified the observed elongation of the projections of the Br atomic columns, suggesting an alternation in the position of the Br atoms perpendicular to the Pb-Br-Pb bonds. Together with molecular dynamics simulations, these results remarkably reveal local distortions in an on-average cubic structure. Additionally, this study provides an approach to prospectively investigating the fundamental degradation mechanisms of MHPs.

The Comparison of Newly Diagnosed Invasive Breast Patient Cohorts in Genomics Evidence Neoplasia Information Exchange Biopharma Collaborative (GENIE-BPC) and Other Real-World Databases.

BACKGROUND: Oncology databases that integrate genomic and clinical data have become valuable resources for precision medicine. However, the generalizability of these databases has not been comprehensively assessed. OBJECTIVES: To describe the demographics, clinical characteristics, treatments, and overall survival of breast cancer cohorts in GENIE-BPC and three other databases. METHODS: This study utilized GENIE-BPC, SEER, SEER-Medicare, and Merative MarketScan Research Databases. Women with invasive breast cancer were identified through EHR, cancer registries or ICD-9/10-CM codes. The ages were 18+ years or per database requirement. Treatments were based on EHR or HCPCS/NDC codes in claims. Overall survival was estimated as time from diagnosis to death. RESULTS: Of female breast cancer patients in GENIE-BPC (n = 775), SEER (n = 548 336), SEER-Medicare (n = 68 914), and Marketscan (n = 109 499) databases, the median ages at initial diagnosis were 44, 62, 74, and 57 years, respectively. A greater proportion of patients in GENIE-BPC, compared to SEER/SEER-Medicare, had higher nuclear grades (%III-%IV: 57% vs. 26%/24%), advanced disease stage (%IV: 25.3% vs. 5%/3.6%), percent of triple negative breast cancer (19.7% vs. 10.2%/8.5%), and receipt of chemotherapy (85.0% vs. NA/22.3%). The 1-, 3-, and 5-year overall survival rates were lower in GENIE-BPC (78.5%, 60.5%, 55.5%) than in SEER (95.8%, 89.5%, 85.5%) and SEER-Medicare (91.6%, 81.4%, 75.0%). CONCLUSION: Breast cancer patients in GENIE-BPC were younger, had more advanced disease, had a higher proportion of triple negative breast cancer and recipients of chemotherapy, and had poorer overall survival. Researchers must use statistical adjustment when extrapolating results (e.g., biomarker prevalence) from GENIE-BPC to the larger breast cancer population.

Hydrophobic evaporable fullerene indanone ketone with low sublimation temperature and amorphous morphology for inverted perovskite solar cells.

A hydrophobic evaporable indano[60] fullerene ketone with low sublimation temperature (CF3-FIDO) was successfully synthesized, providing the fullerene mono-adduct derivative with the lowest sublimation temperature reported to date. The amorphous characteristic of the evaporated film was confirmed by grazing incidence X-ray diffraction (GIXRD) and atomic force microscopy (AFM). Perovskite solar cells using CF3-FIDO as the electron transport layer (ETL) achieved long-term device stability retaining 60% of their initial PCE after 500 h in air.

Provision of Stroke Care Services by Community Disadvantage Status in the US, 2009-2022.

Importance: Stroke center certification is granted to facilities that demonstrate distinct capabilities for treating patients with stroke. A thorough understanding of structural discrimination in the provision of stroke centers is critical for identifying and implementing effective interventions to improve health inequities for socioeconomically disadvantaged populations. Objective: To determine whether (1) hospitals in socioeconomically disadvantaged communities (defined using the Area Deprivation Index) are less likely to adopt any stroke certification and (2) adoption rates differ between entry-level (acute stroke-ready hospitals) and higher-level certifications (primary, thrombectomy capable, and comprehensive) by community disadvantage status. Design, Setting, and Participants: This cohort study used newly collected stroke center data merged with data from the American Hospital Association, Healthcare Cost Report Information datasets, and the US Census. All general acute hospitals in the continental US between January 1, 2009, and December 31, 2022, were included. Data analysis was conducted from July 2023 to May 2024. Main Outcomes and Measures: The primary outcome was the likelihood of hospitals adopting stroke care certification. Cox proportional hazard and competing risk models were used to estimate the likelihood of a hospital becoming stroke certified based on the socioeconomic disadvantage status of the community. Results: Among the 5055 hospitals studied from 2009 to 2022, 2415 (47.8%) never achieved stroke certification, 602 (11.9%) were certified as acute stroke-ready hospitals, and 2038 (40.3%) were certified as primary stroke centers or higher. When compared with mixed-advantage communities, adoption of any stroke certification was most likely to occur near the most advantaged communities (hazard ratio [HR], 1.24; 95% CI, 1.07-1.44) and least likely near the most disadvantaged communities (HR, 0.43; 95% CI, 0.34-0.55). Adoption of acute stroke-ready certification was most likely in mixed-advantage communities, while adoption of higher-level certification was more likely in the most advantaged communities (HR,1.41; 95% CI, 1.22-1.62) and less likely for the most disadvantaged communities (HR, 0.31; 95% CI, 0.21-0.45). After adjusting for population size and hospital capacity, compared with mixed-advantage communities, stroke certification adoption hazard was still 20% lower for relatively disadvantaged communities (adjusted HR, 0.80; 95% CI, 0.73-0.87) and 42% lower for the most disadvantaged communities (adjusted HR, 0.58; 95% CI, 0.45-0.74). Conclusions and Relevance: In this cohort study examining hospital adoption of stroke services, when compared with mixed-advantage communities, hospitals located in the most disadvantaged communities had a 42% lower hazard of adopting any stroke certification and relatively disadvantaged communities had a 20% lower hazard of adopting any stroke certification. These findings suggest that there is a need to support hospitals in disadvantaged communities to obtain stroke certification as a way to reduce stroke disparities.

Structural Inequities In The Adoption Of Percutaneous Coronary Intervention Services By US Hospitals, 2000-20.

Percutaneous coronary intervention (PCI) is a procedure that opens blocked arteries and restores blood flow to the heart. Timely access to hospitals offering PCI services can be a matter of life or death for patients experiencing a heart attack; however, hospitals' adoption of PCI services may vary between communities, posing potential barriers to critical care. Our cohort study of US general acute hospitals during the period 2000-20 examined PCI service adoption across communities stratified by race, ethnicity, income, and rurality and further classified as segregated or integrated. Of 5,260 hospitals, 1,621 offered PCI services in 2020 or before, 630 added PCI services between 2001 and 2010, and 225 added PCI services between 2011 and 2020. Hospitals serving Black, racially segregated communities were 48 percent less likely to adopt PCI services compared with hospitals serving non-Black, racially segregated communities, and hospitals serving Hispanic, ethnically segregated communities were 41 percent less likely to do so than those serving non-Hispanic, ethnically segregated communities. Hospitals in high-income, economically integrated communities were 1.8 times more likely to adopt PCI services than those in high-income, economically segregated communities, and rural hospitals were less likely to do so than urban hospitals. Understanding where services are expanding in relation to community need may aid in successful policy interventions.

Arginine Methylation of DDX3 by PRMT1 Mediates Mitochondrial Homeostasis to Promote Breast Cancer Metastasis.

Dysregulated mitochondrial dynamics and metabolism play important roles in tumorigenesis. Metastasizing tumor cells predominantly utilize mitochondrial metabolism, and regulators of metabolic reprogramming may provide reliable biomarkers for diagnosing cancer metastasis. Here, we identified a type I arginine methyltransferase-DEAD-box polypeptide 3, X-linked (PRMT1-DDX3) axis that promotes breast cancer metastasis by coordinating mitochondrial biogenesis and mitophagy to ensure mitochondrial quality control. Mechanistically, PRMT1 induces arginine methylation of DDX3, which enhances its protein stability and prevents proteasomal degradation. DDX3 mediates mitochondrial homeostasis by translocating to mitochondria where it facilitates phosphatase and tensin homology-induced kinase 1 translation in response to mitochondrial stress. Inhibition of DDX3 suppresses mitochondrial biogenesis and mitophagy, resulting in diminished cancer stemness and metastatic properties. Overall, this study uncovers a mechanism by which the PRMT1-DDX3 axis regulates mitochondrial homeostasis to support breast cancer metastasis, suggesting strategies for targeting metabolic vulnerabilities to treat metastatic breast cancer. Significance: DDX3 is stabilized by PRMT1-mediated arginine methylation and coordinates mitophagy and mitochondrial biogenesis by upregulating PINK1 to facilitate breast cancer progression.

Discovery of differentially expressed proteins for CAR-T therapy of ovarian cancers with a bioinformatics analysis.

Target antigens are crucial for developing chimeric antigen receptor (CAR)-T cells, but their application to ovarian cancers is limited. This study aimed to identify potential genes as CAR-T-cell antigen candidates for ovarian cancers. A differential gene expression analysis was performed on ovarian cancer samples from four datasets obtained from the GEO datasets. Functional annotation, pathway analysis, protein localization, and gene expression analysis were conducted using various datasets and tools. An oncogenicity analysis and network analysis were also performed. In total, 153 differentially expressed genes were identified in ovarian cancer samples, with 60 differentially expressed genes expressing plasma membrane proteins suitable for CAR-T-cell antigens. Among them, 21 plasma membrane proteins were predicted to be oncogenes in ovarian cancers, with nine proteins playing crucial roles in the network. Key genes identified in the oncogenic pathways of ovarian cancers included MUC1, CXCR4, EPCAM, RACGAP1, UBE2C, PRAME, SORT1, JUP, and CLDN3, suggesting them as recommended antigens for CAR-T-cell therapy for ovarian cancers. This study sheds light on potential targets for immunotherapy in ovarian cancers.

Cellular spermine targets JAK signaling to restrain cytokine-mediated autoimmunity.

Prolonged activation of the type I interferon (IFN-I) pathway leads to autoimmune diseases such as systemic lupus erythematosus (SLE). Metabolic regulation of cytokine signaling is critical for cellular homeostasis. Through metabolomics analyses of IFN-ß-activated macrophages and an IFN-stimulated-response-element reporter screening, we identified spermine as a metabolite brake for Janus kinase (JAK) signaling. Spermine directly bound to the FERM and SH2 domains of JAK1 to impair JAK1-cytokine receptor interaction, thus broadly suppressing JAK1 phosphorylation triggered by cytokines IFN-I, IFN-II, interleukin (IL)-2, and IL-6. Peripheral blood mononuclear cells (PBMCs) from individuals with SLE showing decreased spermine concentrations exhibited enhanced IFN-I and lupus gene signatures. Spermine treatment attenuated autoimmune pathogenesis in SLE and psoriasis mice and reduced IFN-I signaling in monocytes from individuals with SLE. We synthesized a spermine derivative (spermine derivative 1 [SD1]) and showed that it had a potent immunosuppressive function. Our findings reveal spermine as a metabolic checkpoint for cellular homeostasis and a potential immunosuppressive molecule for controlling autoimmune disease.

Design and synthesis of 6-C-alkyl-DMDP type nanomolar inhibitors of ß-galactosidase and ß-glucosidase based on broussonetine S and related derivatives.

Broussonetine S (9), its C-1' and C-10' stereoisomers, and their corresponding enantiomers have been synthesized from enantiomeric arabinose-derived cyclic nitrones, with cross metathesis (CM), epoxidation and Keck asymmetric allylation as key steps. Glycosidase inhibition assays showed that broussonetine S (9) and its C-10' epimer (10'-epi-9) were nanomolar inhibitors of bovine liver ß-galactosidase and ß-glucosidase; while their C-1' stereoisomers were 10-fold less potent towards these enzymes. The glycosidase inhibition results and molecular docking calculations revealed the importance of the configurations of pyrrolidine core and C-1' hydroxyl for inhibition potency and spectra. Together with the docking calculations we previously reported for α-1-C-alkyl-DAB derivatives, we designed and synthesized a series of 6-C-alkyl-DMDP derivatives with very simple alkyl chains. The inhibition potency of these derivatives was enhanced by increasing the length of the side chain, and maintained at nanomolar scale inhibitions of bovine liver ß-glucosidase and ß-galactosidase after the alkyl groups are longer than eight or ten carbons for the (6R)-C-alkyl-DMDP derivatives and their 6S epimers, respectively. Molecular docking calculations indicated that each series of 6-C-alkyl-DMDP derivatives resides in the same active site of ß-glucosidase or ß-galactosidase with basically similar binding conformations, and their C-6 long alkyl chains extend outwards along the hydrophobic groove with similar orientations. The increasing inhibitions of ß-glucosidase and ß-galactosidase with the number of carbon atoms in the side chains may be explained by improved adaptability of longer alkyl chains in the hydrophobic grooves. In addition, the lower ß-glucosidase and ß-galactosidase inhibitions of (6S)-C-alkyl-DMDP derivatives than their C-6 R stereoisomers can be attributed to the misfolding of their alkyl chains and resulted decreased adaptability in the hydrophobic groove. The work reported herein is valuable for design and development of more potent and selective inhibitors of ß-galactosidase and ß-glucosidase, which have potential in treatment of lysosomal storage diseases. Furthermore, part of the 6-C-alkyl-DMDP derivatives and their enantiomers were also tested as potential anti-cancer agents; all the compounds tested were found with moderate cytotoxic effects on MKN45 cells, which would indicate potential applications of these iminosugars in development of novel anticancer agents.

In-Hospital Use of Long-Acting Injectable Antipsychotics and Readmission Risk in Patients With First-Admission Schizophrenia in Taiwan.

Importance: Long-acting injectable antipsychotics (LAIs) can help decrease the rate of nonadherence to medications in patients with schizophrenia, but these drugs are underutilized in clinical practice, especially in Asian countries. One strategy for the early prescription of LAIs is to administer the drugs during patients' first admission, when they have more time to absorb medication-related knowledge. Objective: To estimate the prevalence of and risk factors for in-hospital use of LAIs among first-admission patients with schizophrenia in Taiwan and to examine the association of early discontinuation with readmission risk among patients receiving LAIs. Design, Setting, and Participants: This cohort study included data from a claims database for patients with a first admission for schizophrenia at psychiatric wards in Taiwan from 2004 to 2017. Eligible patients were diagnosed with schizophrenia or schizoaffective disorder at discharge and aged between 15 and 64 years. Data analysis was performed from April to September 2022. Exposure: In-hospital use of LAIs with or without early discontinuation. Main Outcome and Measures: Readmission for any psychotic disorder following discharge from first admission, with risk estimated via multivariable survival regression analysis, including the Cox proportional hazards (CPH) model and accelerated failure time (AFT) model. Results: Of the 56 211 patients with a first admission for schizophrenia (mean [SD] age, 38.1 [12.1] years; 29 387 men [52.3%]), 46 875 (83.4%) did not receive any LAIs during admission, 5665 (10.1%) received LAIs with early discontinuation, and 3671 (6.5%) received LAIs without early discontinuation. The prevalence of receiving LAIs increased by 4%, from 15.3% (3863 of 25 251 patients) to 19.3% (3013 of 15 608 patients) between 2004-2008 and 2013-2017. After controlling for sex, year, prior antipsychotic use, age at first admission, and length of stay, the CPH regression analysis revealed that the readmission risk increased among patients receiving LAIs with early discontinuation (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.21-1.30) but decreased among patients receiving LAIs without early discontinuation (aHR, 0.88; 95% CI, 0.84-0.92) compared with patients not receiving LAIs. Results remained similar for the AFT model. Conclusions and Relevance: The incidence of in-hospital use of LAIs among patients with a first admission for schizophrenia has remained low. In this study, early discontinuation of LAIs was associated with readmission risk-specifically, early discontinuation with a higher risk while the lack of early discontinuation with a lower risk compared with treatment with oral antipsychotics alone-which suggests our results have implications for improving the efficacy of LAI administration among patients with a first admission for schizophrenia.

Encouraging online consumers into making better food choices: The power of nature exposure on healthy food choices.

BACKGROUND: online environments can influence food desire and choices. We tested if online calming nature and stressful street environments can affect desire for healthy and unhealthy foods. METHOD: we asked 238 participants (40 ± 14 yrs) to rate their desire (100 mm VAS) for 7 low calorie nutrient rich foods (Healthy) and 7 high calorie nutrient poor foods (Unhealthy), and perceived stress (state anxiety in STAI), before and after imagining themselves in a control, nature park, or busy street condition. RESULTS: participants who imagined themselves being in a nature park had a significant higher desire for Healthy foods, than participants in the busy street condition (p < 0.05). Participants in the busy street condition decreased their desire for Healthy foods after they imagined themselves in a busy street (p < 0.05)). However, perceived stress did not impact the association between condition and desire for low calorie foods nor high calorie foods. CONCLUSION: this study suggests that online environments can have an impact on healthy food desires, which could be of importance for the increased number of food choices which are made in online environments.

Is more better? A multilevel analysis of percutaneous coronary intervention hospital openings and closures on patient volumes.

BACKGROUND: It is unknown how changes in the percutaneous coronary intervention (PCI) "built environment" have impacted PCI volumes at the community, hospital, and patient levels. This study sought to determine how PCI hospital openings and closures effect community- and hospital-level PCI volumes as well as the likelihood of receiving PCI at a low-volume hospital. METHODS: We conducted a retrospective cohort study of 3,966,025 Medicare Fee-For-Service patients in 37,451 zip codes and 2564 U.S. hospitals who underwent PCI from 2006 to 2017. We conducted community-, hospital-, and patient-level analyses using ordinary least squares regressions with fixed effects to determine changes in PCI volumes after PCI hospital openings or closures. RESULTS: Between 2006 and 2017, a total of 17% and 7% of patients lived in communities that experienced PCI hospital openings and closures, respectively. Openings were associated with a 10% increase in community PCI volume, a 2% increase in the share of elective PCI, and a doubling in the likelihood of receiving PCI at a low-volume hospital. In communities with low baseline PCI capacity, openings were associated with a 12% increase in community PCI volume, and in high-capacity communities, an 8% increase. PCI closures were associated with a 9% decrease in community PCI volume in high-capacity communities but no measurable change in low-capacity communities. CONCLUSIONS: PCI service expansion is associated with increased PCI at low-volume hospitals and a greater number of elective procedures. Increased governmental oversight may be necessary to ensure that openings and closures of these specialized services yield the desired benefits.

Development and functional evaluation of a hyaluronic acid coated nano-formulation with kaempferol as a novel intra-articular agent for Knee Osteoarthritis treatment.

Knee osteoarthritis (OA) involves articular cartilage degradation driven mainly by inflammation. Kaempferol (KM), known for its anti-inflammatory property, holds potential for OA treatment. This study investigated the potential of hyaluronic acid (HA)-coated gelatin nanoparticles loaded with KM (HA-KM GNP) for treating knee OA. KM was encapsulated into gelatin nanoparticles (KM GNP) and then coated with HA to form HA-KM GNPs. Physical properties were characterized, and biocompatibility and cellular uptake were assessed in rat chondrocytes. Anti-inflammatory and chondrogenic properties were evaluated using IL-1ß-stimulated rat chondrocytes, compared with HA-coated nanoparticles without KM (HA GNP) and KM alone. Preclinical efficacy was tested in an anterior cruciate ligament transection (ACLT)-induced knee OA rat model treated with intra-articular injection of HA-KM GNP. Results show spherical HA-KM GNPs (88.62 ± 3.90 nm) with positive surface charge. Encapsulation efficiency was 98.34 % with a sustained release rate of 18 % over 48 h. Non-toxic KM concentration was 2.5 µg/mL. In IL-1ß-stimulated OA rat chondrocytes, HA-KM GNP significantly down-regulated RNA expression of IL-1ß, TNF-α, COX-2, MMP-9, and MMP-13, while up-regulating SOX9 compared to HA GNP, and KM. In vivo imaging demonstrated significantly higher fluorescence intensity within rat knee joints for 3 hours post HA-KM GNP injection compared with KM GNP (185.2% ± 34.1% vs. 45.0% ± 16.7%). HA-KM GNP demonstrated significant effectiveness in reducing subchondral sclerosis, attenuating inflammation, inhibiting matrix degradation, restoring cartilage thickness, and reducing the severity of OA in the ACLT rat model. In conclusion, HA-KM GNP holds promise for knee OA therapy.

Investigating the neural substrate variations between easy and challenging creative association tasks during product design within an fMRI scanner.

In practice, individuals strive to develop highly original and valuable creative products within specific limitations. However, previous functional Magnetic Resonance Imaging (fMRI) studies focused on divergent-thinking tasks without considering the "valuableness" of an idea. Additionally, different types of creative tasks (e.g., the easier association vs. the harder association task) may engage distinct cognitive processes. This study aimed to investigate the underlying neural mechanisms associated with different types of creative thinking, specifically focusing on the generation of the most original and valuable creative product within an fMRI scanner. Twenty-one college students participated in a block design study. During each trial, participants were instructed to draw the most original and valuable product inspired by a given figure. The findings revealed that, in comparison to the harder association task, the easier association task led to broader activation across multiple brain regions. However, this broader activation resulted in inefficient thinking and poorer creative performance. Notably, the orbitofrontal cortex exhibited activation across various creativity tasks and displayed connectivity with several seed brain regions, highlighting the importance of decision-making when only one original and valuable product design is allowed. Furthermore, the complex functional connectivity observed between different brain networks reflects the intricate nature of creative thinking. To conclude, widespread activation of brain regions does not necessarily indicate superior creativity. Instead, optimal creative performance within constraints is achieved through an efficient utilization of association for generating innovative ideas, inhibition for suppressing unoriginal ideas, and decision-making to select the most creative idea.

The nematode-trapping fungus Arthrobotrys oligospora detects prey pheromones via G protein-coupled receptors.

The ability to sense prey-derived cues is essential for predatory lifestyles. Under low-nutrient conditions, Arthrobotrys oligospora and other nematode-trapping fungi develop dedicated structures for nematode capture when exposed to nematode-derived cues, including a conserved family of pheromones, the ascarosides. A. oligospora senses ascarosides via conserved MAPK and cAMP-PKA pathways; however, the upstream receptors remain unknown. Here, using genomic, transcriptomic and functional analyses, we identified two families of G protein-coupled receptors (GPCRs) involved in sensing distinct nematode-derived cues. GPCRs homologous to yeast glucose receptors are required for ascaroside sensing, whereas Pth11-like GPCRs contribute to ascaroside-independent nematode sensing. Both GPCR classes activate conserved cAMP-PKA signalling to trigger trap development. This work demonstrates that predatory fungi use multiple GPCRs to sense several distinct nematode-derived cues for prey recognition and to enable a switch to a predatory lifestyle. Identification of these receptors reveals the molecular mechanisms of cross-kingdom communication via conserved pheromones also sensed by plants and animals.