Film swelling and contaminant adsorption at polymer coated surfaces: Insights from density functional theory.

Designing coatings and films that can protect surfaces is important in a wide variety of applications from corrosion prevention to anti-fouling. These systems are challenging from a modeling perspective because they are invariably multicomponent, which quickly leads to an expansive design space. At a minimum, the system has a substrate, a film (often composed of a polymeric material), a ubiquitous carrier solvent, which may be either a vapor or liquid phase, and one or more contaminants. Each component has an impact on the effectiveness of coating. This paper focuses on films that are used as a barrier to surface contamination, but the results also extend to surface coatings that are designed to extract a low density species from the fluid phase as in liquid chromatography. A coarse-grained model is developed using Yukawa potentials that encompasses both repulsive and attractive interactions among the species. Classical density functional theory calculations are presented to show how contaminant adsorption is controlled by the molecular forces in the system. Two specific vectors through the parameter space are considered to address likely experimental manipulations that change either the solvent or the polymer in a system. We find that all the adsorption results can be unified by considering an appropriate combination of molecular parameters. As a result, these calculations provide a link between molecular interactions and film performance and may serve to guide the rational design of films.

Dynamics of amylopectin granule accumulation during the course of the chronic Toxoplasma infection is linked to intra-cyst bradyzoite replication.

The contribution of amylopectin granules (AG), comprised of a branched chain storage homopolymer of glucose, to the maintenance and progression of the chronic Toxoplasma gondii infection has remained undefined. Here we describe the role of AG in the physiology of encysted bradyzoites by using a custom developed imaging-based application AmyloQuant that permitted quantification of relative levels of AG within in vivo derived tissue cysts during the initiation and maturation of the chronic infection. Our findings establish that AG are dynamic entities, exhibiting considerable heterogeneity among tissue cysts at all post infection time points examined. Quantification of relative AG levels within tissue cysts exposes a previously unrecognized temporal cycle defined by distinct phases of AG accumulation and utilization over the first 6 weeks of the chronic phase. This AG cycle is temporally coordinated with overall bradyzoite mitochondrial activity implicating amylopectin in the maintenance and progression of the chronic infection. In addition, the staging of AG accumulation and it rapid utilization within encysted bradyzoites was associated with a burst of coordinated replication. As such our findings suggest that AG levels within individual bradyzoites, and across bradyzoites within tissue cysts may represent a key component in the licensing of bradyzoite replication, intimately linking stored metabolic potential to the course of the chronic infection. This extends the impact of AG beyond the previously assigned role that focused exclusively on parasite transmission. These findings force a fundamental reassessment of the chronic Toxoplasma infection, highlighting the critical need to address the temporal evolution of this crucial stage in the parasite life cycle.

Does the Primary Tumor Site Drive Biology for Patients With Synovial Sarcoma?

OBJECTIVE: We evaluated survival outcomes by primary tumor site in synovial sarcoma (SS) patients with localized and metastatic disease at diagnosis. METHODS: We conducted a retrospective review of 504 SS patients diagnosed from 1974 to 2020. Kaplan-Meier method, log-rank test, and Cox-proportional hazards regression were used. RESULTS: Among 504 patients, 401 (79.6%) presented with localized disease, and 103 (20.4%) with metastases. For patients with localized disease, (1) 5-year OS by tumor site was as follows: 80% (95% CI, 67%-89%) for head/neck, 30% (95% CI, 18%-42%) for intrathoracic, 51% (95% CI, 35%-65%) for abdomen/pelvis, 71% (95% CI, 62%-79%) for proximal-extremity, and 83% (71%, 91%) for distal-extremity. (2) On multivariable analysis, tumor site (compared with proximal-extremity: intrathoracic tumors [HR: 1.95; 95% CI, 1.22-3.16]; hand/foot [HR: 0.52; 95% CI, 0.28-0.97]), tumor size (compared with <5 cm, 5-10 cm [HR: 1.80; 95% CI, 1.14-2.85]; ≥10 cm [HR: 4.37; 95% CI, 2.69-7.11]), and use of neo/adjuvant radiation (HR: 0.54; 95% CI, 0.37-0.79) remained significantly associated with OS. For patients with metastatic disease, (1) 5-year OS was 12% (95% CI, 6%-21%) and (2) the only factor that remained significantly associated with OS on multivariable analysis was surgical resection for the primary tumor (HR: 0.14; 95% CI, 0.08-0.26). CONCLUSIONS: The primary tumor location plays a significant role in predicting outcomes for patients with localized SS. Even though patients present with metastatic disease, surgical resection of the primary tumor improves their survival. These findings are critical for patient counseling and designing a personalized treatment plan that reflects the corresponding outcomes.

Outcomes for Mechanically Ventilated Patients With Acute Myocardial Infarction Admitted to Medical vs Cardiac Intensive Care Units.

Background: Acute myocardial infarction (AMI) remains a common reason for admission to the intensive care unit (ICU). However, there is limited data comparing outcomes for patients with AMI admitted to specific ICUs. Objectives: The purpose of this study was to assess clinical outcomes between patients with AMI requiring invasive mechanical ventilation admitted to the medical ICU (MICU) compared to cardiac (CICU). Methods: We utilized the Vizient Clinical Data Base to identify patients with a primary diagnosis of AMI between October 2015 and December 2019 and requiring invasive mechanical ventilation. Using multivariable logistic regression, we compared clinical outcomes for patients admitted to the MICU vs CICU. Results: We identified 12,639 patients, 25.2% (n = 3,185) of which were admitted to a MICU and 74.8% (n = 9,454) to a CICU. Patients admitted to a CICU were more likely to present with STEMI (57.0% vs 42.8%), cardiogenic shock (46.0% vs 37.4%), and require mechanical circulatory support and vasoactive medications (all, P < 0.001). Median ventilator days were 4 days in both ICUs and not statistically different after multivariable adjustment (P = 0.81). In-hospital mortality was 42.7% compared to 41.3% for MICU vs CICU admissions, respectively (P = 0.15). After multivariable adjustment, CICU admission was associated with lower in-hospital mortality (OR: 0.85, 95% CI: 0.78-0.93, P = 0.001), which persisted when stratified by cardiogenic shock, cardiac arrest, STEMI, largest hospital size (>750 beds), and teaching hospitals (all, P < 0.05). Conclusions: Admission to the CICU, as compared to MICU, was associated with lower in-hospital mortality for patients with AMI. These findings may support optimal triage of critically ill patients with AMI.

Progression of Gummy Stem Blight Epidemics on Watermelon with and without Fungicide Inputs.

Gummy stem blight (GSB), caused primarily by the fungus Stagonosporopsis citrulli in the southeastern United States, affects cucurbits and is particularly destructive on watermelon. Previous epidemiological models of GSB constructed for greenhouse cucumber showed leaf wetness and temperature were the primary and secondary environmental factors, respectively, that explained epidemic progress. The objective of this study was to construct a model that predicted GSB severity on field-grown watermelon based on environmental factors. Disease and weather data from six fungicide experiments in Charleston, South Carolina, in spring and fall 1997 and fall 2017, 2018, 2019, and 2022 were used as inputs. Fungicide treatments were grouped into nonsprayed, protectant (chlorothalonil and mancozeb) and GSB-specific (cyprodinil, difenoconazole and fludioxonil) applications. Cumulative hours of leaf wetness was the primary explanatory variable that modeled the increase in proportion GSB severity ≥2% across all epidemics. Incorporation of temperature or other environmental variables did not improve the model. Fit of the overall model was evaluated with k-fold cross validation, where individual experiments were each excluded from the model fitting process. Slopes of predicted disease progress curves were lowered significantly compared to the nonsprayed treatments by applications of protectant fungicides. Applying GSB-specific fungicides alternated with chlorothalonil further reduced slope values. The model successfully predicted progress of GSB epidemics under different weather patterns and fungicide applications.

Peptide nucleic acids can form hairpins and bind RNA-binding proteins.

RNA-binding proteins (RBPs) are a major class of proteins that interact with RNAs to change their fate or function. RBPs and the ribonucleoprotein complexes they constitute are involved in many essential cellular processes. In many cases, the molecular details of RBP:RNA interactions differ between viruses, prokaryotes and eukaryotes, making prokaryotic and viral RBPs good potential drug targets. However, targeting RBPs with small molecules has so far been met with limited success as RNA-binding sites tend to be extended, shallow and dynamic with a mixture of charged, polar and hydrophobic interactions. Here, we show that peptide nucleic acids (PNAs) with nucleic acid-like binding properties and a highly stable peptide-like backbone can be used to target some RBPs. We have designed PNAs to mimic the short RNA stem-loop sequence required for the initiation of prokaryotic signal recognition particle (SRP) assembly, a target for antibiotics development. Using a range of biophysical and biochemical assays, the designed PNAs were demonstrated to fold into a hairpin structure, bind the targeted protein and compete with the native RNA hairpin to inhibit SRP formation. To show the applicability of PNAs against other RBPs, a PNA was also shown to bind Nsp9 from SARS-CoV-2, a protein that exhibits non-sequence-specific RNA binding but preferentially binds hairpin structures. Taken together, our results support that PNAs can be a promising class of compounds for targeting RNA-binding activities in RBPs.

Slipped capital femoral epiphysis: emphasis on early recognition and potential pitfalls.

Slipped capital femoral epiphysis is a shearing injury through the growth plate of the proximal femur and is the most common hip disorder in adolescence. Delays in diagnosis persist across practice settings despite ongoing innovations in imaging. Recent insights into pathomechanics highlight the importance of femoral head surface morphology and rotational microinstability centered at the epiphyseal tubercle in causing early physeal changes, which can be detected on imaging prior to frank slip. Scrutiny of physeal morphology and comparison to the contralateral hip is critical at all stages of disease progression, and improper technique may result in undue diagnostic delay. Selective use of cross-sectional imaging can be helpful for troubleshooting equivocal early slips and can inform operative technique and adjuvant therapy candidacy in more severe cases. This review provides a comprehensive approach to imaging suspected slipped capital femoral epiphysis, with an emphasis on early detection and potential pitfalls.

Zoom Boom or Bust? Understanding Post-Pandemic Interest in Facial Plastic Surgery via Google Trends.

OBJECTIVE: To understand post-pandemic interest in plastic surgery procedures via Joinpoint analysis of Google Trends search data. METHODS: Google Trends was used to quantify search volumes from January 2019-December 2022 for select cosmetic face and body procedures in the United States. A keyword analytic tool (Keywords Everywhere) extracted absolute search volumes (average monthly searches). Joinpoint analysis assessed search trends over time reported as monthly percentage change (MPC). RESULTS: All procedures queried, including a non-cosmetic control (cataract surgery), demonstrated expected declines at the start of the COVID-19 pandemic. Blepharoplasty, face lift, neck lift, and Botox demonstrated statistically significant increase in search volumes that remained elevated relative to pre-pandemic levels. Rhinoplasty, fillers, and abdominoplasty interest increased initially followed by return to pre-pandemic levels by the end of 2022. The remainder of search terms did not show a clear temporal associated with COVID-19 lockdowns. CONCLUSION: The "Zoom Boom" appears to be a real phenomenon reflected by sustained increase in public interest in relation to facial plastic procedures. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

Management of Shoulder Instability in the Overhead Athletes.

Overhead athletes with anterior, posterior, and multidirectional shoulder instability present with a wide range of symptoms, especially considering the injury mechanism and affected supportive structures. As such, the management of shoulder instability is widely variable and relies on rehabilitation, operative management, and sport-specific considerations, such as positional and seasonal demands on the athlete. Biomechanical analysis may further aid in the recovery process or serve as a predictive tool to identify an increased risk for injury.

The low-density lipoprotein receptor contributes to carotenoid homeostasis by regulating tissue uptake and fecal elimination.

OBJECTIVE: Carotenoids are lipophilic plant molecules with antioxidant properties. Some carotenoids such as ß-carotene also serve as vitamin A precursors, playing a key role in human health. Carotenoids are transported in lipoproteins with other lipids such as cholesterol, however, the mechanisms responsible for carotenoid storage in tissues and their non-enzymatic elimination remain relatively unexplored. The goal of this study was to examine the contribution of the low-density lipoprotein receptor (LDLR) in the bodily distribution and disposal of carotenoids. METHODS: We employed mice lacking one or both carotenoid-cleaving enzymes as suitable models for carotenoid accumulation. We examined the contribution of LDLR in carotenoid distribution by crossbreeding these mice with Ldlr-/- mice or overexpressing LDLR in the liver. RESULTS: Our results show that LDLR plays a dual role in carotenoid homeostasis by simultaneously favoring carotenoid storage in the liver and adipose tissue while facilitating their fecal elimination. CONCLUSIONS: Our results highlight a novel role of the LDLR in carotenoid homeostasis, and unveil a previously unrecognized disposal pathway for these important bioactive molecules.

The health and economic burden of breathlessness, Australia, 2019: a national survey.

29 August 2024: This article published in Early View in error. The article is under embargo and will republish on 16th September 2024.

Serum proteomics reveal APOE-ε4-dependent and APOE-ε4-independent protein signatures in Alzheimer's disease.

A deeper understanding of the molecular processes underlying late-onset Alzheimer's disease (LOAD) could aid in biomarker and drug target discovery. Using high-throughput serum proteomics in the prospective population-based Age, Gene/Environment Susceptibility-Reykjavik Study (AGES) cohort of 5,127 older Icelandic adults (mean age, 76.6 ± 5.6 years), we identified 303 proteins associated with incident LOAD over a median follow-up of 12.8 years. Over 40% of these proteins were associated with LOAD independently of APOE-ε4 carrier status, were implicated in neuronal processes and overlapped with LOAD protein signatures in brain and cerebrospinal fluid. We identified 17 proteins whose associations with LOAD were strongly dependent on APOE-ε4 carrier status, with mostly consistent associations in cerebrospinal fluid. Remarkably, four of these proteins (TBCA, ARL2, S100A13 and IRF6) were downregulated by APOE-ε4 yet upregulated due to LOAD, a finding replicated in external cohorts and possibly reflecting a response to disease onset. These findings highlight dysregulated pathways at the preclinical stages of LOAD, including those both independent of and dependent on APOE-ε4 status.

Characteristics and Outcomes of Adults With Congenital Heart Disease in the Cardiac Intensive Care Unit.

Background: Little is known regarding the characteristics, treatment patterns, and outcomes in patients with adult congenital heart disease (ACHD) admitted to cardiac intensive care units (CICUs). Objectives: The authors sought to better define the contemporary epidemiology, treatment patterns, and outcomes of ACHD admissions in the CICU. Methods: The Critical Care Cardiology Trials Network is a multicenter network of CICUs in North America. Participating centers contributed prospective data from consecutive admissions during 2-month annual snapshots from 2017 to 2022. We analyzed characteristics and outcomes of admissions with ACHD compared with those without ACHD. Multivariable logistic regression was used to assess mortality in ACHD vs non-ACHD admissions. Results: Of 23,299 CICU admissions across 42 sites, there were 441 (1.9%) ACHD admissions. Shunt lesions were most common (46.1%), followed by right-sided lesions (29.5%) and complex lesions (28.7%). ACHD admissions were younger (median age 46 vs 67 years) than non-ACHD admissions. ACHD admissions were more commonly for heart failure (21.3% vs 15.7%, P < 0.001), general medical problems (15.6% vs 6.0%, P < 0.001), and atrial arrhythmias (8.6% vs 4.9%, P < 0.001). ACHD admissions had a higher median presenting Sequential Organ Failure Assessment score (5.0 vs 3.0, P < 0.001). Total hospital stay was longer for ACHD admissions (8.2 vs 5.9 days, P < 0.01), though in-hospital mortality was not different (12.7% vs 13.6%; age- and sex-adjusted OR: 1.19 [95% CI: 0.89-1.59], P = 0.239). Conclusions: This study illustrates the unique aspects of the ACHD CICU admission. Further investigation into the best approach to manage specific ACHD-related CICU admissions, such as cardiogenic shock and acute respiratory failure, is warranted.

Medically not yet explained symptoms in hypothyroidism.

Persistent symptoms are common in the general population and even more so in people with hypothyroidism. When symptoms are unexplained and brought to medical attention, they can be referred to as medically not yet explained symptoms (MNYES), a term preferred to other descriptors by patients, care-givers and experts. MNYES might be neglected by endocrinologists or misattributed to hypothyroidism. Awareness of MNYES could open up more effective and less harmful interventions for patients who present to endocrinologists with unexplained symptoms than costly over-investigations and over-treatment with thyroid hormones (such as levothyroxine and liothyronine). The role of the endocrinologist is to recognize and acknowledge that MNYES could be underlying a patient's presentation, to communicate effectively with the patient and others involved in the patient's care, to apply a 'two-track approach' in management by paying equal attention to physical and psychosocial contributors, and to collaborate with other relevant health professionals. Categorization of patients into levels of risk for symptom deterioration helps in selecting suitable therapies. Effective management of MNYES demands time, training, expertise and resources.

Examining factors associated with self-reported cognitive functioning in elite military settings: considerations of combat experiences and post-traumatic stress symptomology.

Exposure to traumatic events is associated with post-traumatic stress symptomology (PTSS) in a variety of populations. PTSS is also associated with self-reported everyday cognitive failures, which are acknowledged attentional lapses experienced in one's naturalistic everyday environment. While a growing literature suggests that PTSS is associated with both traumatic events and attentional functions, little is known regarding similar associations in elite military cohorts, such as Special Operations Forces (SOF) personnel. Herein, we investigate if prior combat experience is associated with everyday cognitive failures, while considering the possible mediating role of PTSS. SOF personnel (N = 119) completed self-report questionnaires assessing prior combat experience, PTSS, and everyday cognitive failures. Direct and indirect associations between these metrics were examined using structural equation modeling. Mediation analyses revealed that the correspondence between combat experiences and everyday cognitive failures is mediated by the severity of subclinical levels of PTSS. Such findings suggest that greater attention to subclinical PTSS is warranted due to its significant association with everyday cognitive failures that may contribute to deleterious mission-related failures in high-demand tactical professionals, such as SOF.