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Abstract Background Although prior research has estimated the overarching cost burden of heart failure (HF), a thorough analysis examining medical expense differences and trends, specifically among commercially insured patients with heart failure, is still lacking. Thus, the study aims to examine historical trends and differences in medical costs for commercially insured heart failure patients in the United States from 2006 to 2021. Methods A population-based, cross-sectional analysis of medical and pharmacy claims data (IQVIA PharMetrics® Plus for Academic) from 2006 to 2021 was conducted. The cohort included adult patients (age > = 18) who were enrolled in commercial insurance plans and had healthcare encounters with a primary diagnosis of HF. The primary outcome measures were the average total annual payment per patient and per cost categories encompassing hospitalization, surgery, emergency department (ED) visits, outpatient care, post-discharge care, and medications. The sub-group measures included systolic, diastolic, and systolic combined with diastolic, age, gender, comorbidity, regions, states, insurance payment, and self-payment. Results The study included 422,289 commercially insured heart failure (HF) patients in the U.S. evaluated from 2006 to 2021. The average total annual cost per patient decreased overall from $9,636.99 to $8,201.89, with an average annual percentage change (AAPC) of -1.11% (95% CI: -2% to -0.26%). Hospitalization and medication costs decreased with an AAPC of -1.99% (95% CI: -3.25% to -0.8%) and − 3.1% (95% CI: -6.86–0.69%). On the other hand, post-discharge, outpatient, ED visit, and surgery costs increased by an AAPC of 0.84% (95% CI: 0.12–1.49%), 4.31% (95% CI: 1.03–7.63%), 7.21% (95% CI: 6.44–8.12%), and 9.36% (95% CI: 8.61–10.19%). Conclusions The study’s findings reveal a rising trend in average total annual payments per patient from 2006 to 2015, followed by a subsequent decrease from 2016 to 2021. This decrease was attributed to the decline in average patient costs within the Medicare Cost insurance category after 2016, coinciding with the implementation of the Medicare Access and CHIP Reauthorization Act (MACRA) of 2015. Additionally, expenses related to surgical procedures, emergency department (ED) visits, and outpatient care have shown substantial growth over time. Moreover, significant differences across various variables have been identified.

Background Obesity is associated with resistance to the metabolic (glucose uptake) and vascular (nitric‐oxide mediated dilation and microvascular recruitment) actions of insulin. These vascular effects contribute to insulin sensitivity by increasing tissue delivery of glucose. Studies by us and others suggest that sympathetic activation contributes to insulin resistance to glucose uptake. Here we tested the hypothesis that sympathetic activation contributes to impaired insulin‐mediated vasodilation in adult subjects with obesity. Methods and Results In a randomized crossover study, we used a euglycemic hyperinsulinemic clamp in 12 subjects with obesity to induce forearm arterial vasodilation (forearm blood flow) and microvascular recruitment (contrast‐enhanced ultrasonography) during an intrabrachial infusion of saline (control) or phentolamine (sympathetic blockade). Insulin increased forearm blood flow on both study days (from 2.21±1.22 to 4.89±4.21 mL/100 mL per min, P=0.003 and from 2.42±0.89 to 7.19±3.35 mL/100 mL per min, P=0.002 for the intact and blocked day, respectively). Sympathetic blockade with phentolamine resulted in a significantly greater increase in microvascular flow velocity (∆microvascular flow velocity: 0.23±0.65 versus 2.51±3.01 arbitrary intensity units (AIU/s) for saline and phentolamine respectively, P=0.005), microvascular blood volume (∆microvascular blood volume: 1.69±2.45 versus 3.76±2.93 AIU, respectively, P=0.05), and microvascular blood flow (∆microvascular blood flow: 0.28±0.653 versus 2.51±3.01 AIU2/s, respectively, P=0.0161). To evaluate if this effect was not due to nonspecific vasodilation, we replicated the study in 6 subjects with obesity comparing intrabrachial infusion of phentolamine to sodium nitroprusside. At doses that produced similar increases in forearm blood flow, insulin‐induced changes in microvascular flow velocity were greater during phentolamine than sodium nitroprusside (%microvascular flow velocity=58% versus 29%, respectively, P=0.031). Conclusions We conclude that sympathetic activation impairs insulin‐mediated microvascular recruitment in adult subjects with obesity.

Summary: Mechanistic Target of Rapamycin Complex 1 (mTORC1) is a master metabolic regulator that is active in nearly all proliferating eukaryotic cells; however, it is unclear whether mTORC1 activity changes throughout the cell cycle. We find that mTORC1 activity oscillates from lowest in mitosis/G1 to highest in S/G2. The interphase oscillation is mediated through the TSC complex but is independent of major known regulatory inputs, including Akt and Mek/Erk signaling. By contrast, suppression of mTORC1 activity in mitosis does not require the TSC complex. mTORC1 has long been known to promote progression through G1. We find that mTORC1 also promotes progression through S and G2 and is important for satisfying the Chk1/Wee1-dependent G2/M checkpoint to allow entry into mitosis. We also find that low mTORC1 activity in G1 sensitizes cells to autophagy induction in response to partial mTORC1 inhibition or reduced nutrient levels. Together, these findings demonstrate that mTORC1 is differentially regulated throughout the cell cycle, with important phase-specific consequences for proliferating cells.

Background Global longitudinal strain (GLS) is a sensitive measure of left ventricular function and a risk marker in severe aortic stenosis. We sought to determine whether biomarkers of cardiac damage (cardiac troponin) and stress (NT-proBNP [N-terminal pro-B-type natriuretic peptide]) could complement GLS to identify patients with severe aortic stenosis at highest risk. Methods and Results From a multicenter prospective cohort of patients with symptomatic severe aortic stenosis who underwent transcatheter aortic valve implantation, we measured absolute GLS (aGLS), cardiac troponin, and NT-proBNP at baseline in 499 patients. Left ventricular ejection fraction 2; P≤0.002 for each) when the other biomarker was elevated, but not when the other biomarker was normal (interaction P=0.015). Conclusions Among patients with symptomatic severe aortic stenosis undergoing transcatheter aortic valve implantation, elevations in circulating cardiac troponin and NT-proBNP are more common as GLS worsens. Biomarkers of cardiac damage and stress are independently associated with mortality after transcatheter aortic valve implantation, whereas GLS is not. These findings may have implications for risk stratification of asymptomatic patients to determine optimal timing of valve replacement.

Per- and polyfluoroalkyl substances (PFAS) are diverse synthetic chemicals manufactured over seven decades. It is an aliphatic molecule with a basic hydrophobic structure of carbon and fluorine linked to a hydrophilic end group. Due to their physicochemical properties associated with the unique structure, PFAS has been used in a wide variety of applications including aqueous film-forming foams (AFFF), paper, carpets, non-stick cookware, etc. as they make products resistant to water, heat, and stains. These molecules have drawn great attention recently for their unique properties, high stability and low degradability, and so-called “Forever Chemicals”. PFAS has the strongest carbon-fluorine bond which makes them persistent in the environment. Hence it contaminates natural resources and endangers public health. This review discusses the discovery, development, and evolution of PFAS from the wonder chemical era to a nightmare chemical era, exposure and its impacts on human health and the environment, current remediation techniques, and future trends of PFAS molecules and related products. The primary objective of this review is to identify knowledge gaps on PFAS contamination, remediation methods, and possible PFAS alternatives.

BackgroundAs primary total knee arthroplasty volume continues to increase, so will the number of revision total knee arthroplasty (rTKA) procedures. The purpose of this study is to provide an updated perspective on the incidence, indications, and financial burden of rTKA in the United States.Material and methodsThis was a retrospective epidemiologic analysis using the National Inpatient Sample. International Classification of Diseases ninth and tenth revision codes were used to identify patients who underwent rTKA and create cohorts based on rTKA indications from 2012 to 2019. National and regional trends for length of stay, cost, and discharge location were evaluated.ResultsA total of 505,160 rTKA procedures were identified. The annual number of rTKA procedures increased by 29.6% over the study period (56,490 to 73,205). The top 3 indications for rTKA were aseptic loosening (23.1%), periprosthetic joint infection (PJI) (20.4%), and instability (11.0%). Over the study period, the proportion of patients discharged to skilled nursing facility decreased from 31.7% to 24.1% (P < .001). Hospital length of stay decreased from 4.0 days in 2012 to 3.8 days in 2019 (P < .001). Hospital costs increased by $1300 from $25,730 to $27,077 (P < .001). The proportion of rTKA cases performed at urban academic centers increased (52.1% to 74.3%, P < .001) while that at urban nonacademic centers decreased (39.0% to 19.2%, P < .001).ConclusionThe top 3 indications for rTKA were aseptic loosening, PJI, and instability, with PJI becoming the most common indication in 2019. These cases are increasingly being performed at urban academic centers and away from urban nonacademic centers.Level of evidence3 (Retrospective cohort study).

Background Left ventricular hypertrophy (LVH) is associated with increased mortality risk and rehospitalization after transcatheter aortic valve replacement among those with severe aortic stenosis. Whether cardiac troponin (cTnT) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) risk stratify patients with aortic stenosis and without LVH is unknown. Methods and Results In a multicenter prospective registry of 923 patients with severe aortic stenosis undergoing transcatheter aortic valve replacement, we included 674 with core-laboratory-measured LV mass index, cTnT, and NT-proBNP. LVH was defined by sex-specific guideline cut-offs and elevated biomarker levels were based on age and sex cut-offs. Adjusted Cox proportional hazards models evaluated associations between LVH and biomarkers and all-cause death out to 5 years. Elevated cTnT and NT-proBNP were present in 82% and 86% of patients with moderate/severe LVH, respectively, as compared with 66% and 69% of patients with no/mild LVH, respectively (P

Over the past 30 years there have been numerous large-scale and longitudinal psychiatric research efforts to improve our understanding and treatment of mental health conditions. However, despite the huge effort by the research community and considerable funding, we still lack a causal understanding of most mental health disorders. Consequently, the majority of psychiatric diagnosis and treatment still operates at the level of symptomatic experience, rather than measuring or addressing root causes. This results in a trial-and-error approach that is a poor fit to underlying causality with poor clinical outcomes. Here we discuss how a research framework that originates from exploration of causal factors, rather than symptom groupings, applied to large scale multi-dimensional data can help address some of the current challenges facing mental health research and, in turn, clinical outcomes. Firstly, we describe some of the challenges and complexities underpinning the search for causal drivers of mental health conditions, focusing on current approaches to the assessment and diagnosis of psychiatric disorders, the many-to-many mappings between symptoms and causes, the search for biomarkers of heterogeneous symptom groups, and the multiple, dynamically interacting variables that influence our psychology. Secondly, we put forward a causal-orientated framework in the context of two large-scale datasets arising from the Adolescent Brain Cognitive Development (ABCD) study, the largest long-term study of brain development and child health in the United States, and the Global Mind Project which is the largest database in the world of mental health profiles along with life context information from 1.4 million people across the globe. Finally, we describe how analytical and machine learning approaches such as clustering and causal inference can be used on datasets such as these to help elucidate a more causal understanding of mental health conditions to enable diagnostic approaches and preventative solutions that tackle mental health challenges at their root cause.

Electrocatalytic proton exchange membranes (PEMs) represent a promising avenue for advancing the field of electrochemical energy conversion and storage by combining the proton-conducting function of PEMs with enhanced catalytic activity by incorporation of metal ions. Here, we systematically studied the ZnO-based metal-organic framework (MOF) and found the introduction of pegylated ZnO to the (diethyl methylamine)/(H2PO4) matrix to form the p-type conducting MOF membrane with a bandgap of 3.67 eV. This membrane not only has a high protonic conductivity of 0.027 S/cm at 300 K with a transference number >0.99 but also possesses high activity (Tafel slope ∼36 mV/decade). The high reaction kinetics supported by finite element modeling simulations shows its ability to produce efficient and sustainable hydrogen. Our results suggest high current density of 1.52 mA/cm2, a turn over frequency [H2 (s−1)] ∼0.474×1018s−1, and a stability of 168 h in neutral medium (pH = 7). This work will enhance new strategies for fabricating membranes with ionic liquid in order to get membranes with protonic conductivity along with high activity for large-scale water electrolysis.

Background: Component malpositioning and joint malalignment following unicompartmental knee arthroplasty (UKA) increase the risk for revision. This study investigates whether accelerometer-based navigation (NAV) decreases radiographic outliers with respect to component placement and joint alignment in comparison to conventional instrumentation in UKA. Methods: A radiographic review of UKAs was performed by a single surgeon following adoption of an accelerometry-guided navigation system (OrthAlign, Aliso Viejo, CA). This cohort was then compared to previous patients undergoing UKA with conventional instrumentation. Six-week postoperative radiographs were used to compare femoral coronal and sagittal angles, tibial coronal and sagittal angles, the net coronal angle, tibial component rotation, and medial tibial overhang. Outliers in implant positioning were compared between groups. Patient variables including age, gender, body mass index, American Society of Anesthesiology, and surgical time (incision until the start of closure) were also compared between groups. Results: Eighty-eight UKA’s were reviewed (49 conventional instrumentation [CI] patients; 39 NAV patients). Using 2-sample t-tests, no significant differences were found in patient demographics, radiographic parameters, and operative times between the CI and NAV cohorts. Using chi-squared tests, no significant difference was found in the number of radiographic outliers between the CI and NAV cohorts. Conclusions: Our study found that a high-volume UKA surgeon achieved a low rate of radiographic outliers in both NAV and CI cohorts. This data suggests that NAV is no different from conventional instrumentation with respect to implant positioning, overall joint alignment, and operative time when used by a high-volume UKA surgeon.

AimTo examine individual variability between perceived physical features and hormones of pubertal maturation in 9-10-year-old children as a function of sociodemographic characteristics.MethodsCross-sectional metrics of puberty were utilized from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study-a multi-site sample of 9-10 year-olds (n = 11,875)-and included perceived physical features via the pubertal development scale (PDS) and child salivary hormone levels (dehydroepiandrosterone and testosterone in all, and estradiol in females). Multi-level models examined the relationships among sociodemographic measures, physical features, and hormone levels. A group factor analysis (GFA) was implemented to extract latent variables of pubertal maturation that integrated both measures of perceived physical features and hormone levels.ResultsPDS summary scores indicated more males (70%) than females (31%) were prepubertal. Perceived physical features and hormone levels were significantly associated with child's weight status and income, such that more mature scores were observed among children that were overweight/obese or from households with low-income. Results from the GFA identified two latent factors that described individual differences in pubertal maturation among both females and males, with factor 1 driven by higher hormone levels, and factor 2 driven by perceived physical maturation. The correspondence between latent factor 1 scores (hormones) and latent factor 2 scores (perceived physical maturation) revealed synchronous and asynchronous relationships between hormones and concomitant physical features in this large young adolescent sample.ConclusionsSociodemographic measures were associated with both objective hormone and self-report physical measures of pubertal maturation in a large, diverse sample of 9-10 year-olds. The latent variables of pubertal maturation described a complex interplay between perceived physical changes and hormone levels that hallmark sexual maturation, which future studies can examine in relation to trajectories of brain maturation, risk/resilience to substance use, and other mental health outcomes.

Iron redox flow batteries (IRFBs) are cost-efficient RFBs that have the potential to develop low-cost grid energy storage. Electrode kinetics are pivotal in defining the cycle life and energy efficiency of the battery. In this study, graphite felt (GF) is heat-treated at 400, 500 and 600 °C, and its physicochemical and electrochemical properties are studied using XPS, FESEM, Raman and cyclic voltammetry. Surface morphology and structural changes suggest that GF heat-treated at 500 °C for 6 h exhibits acceptable thermal stability while accessing the benefits of heat treatment. Specific capacitance was calculated for assessing the wettability and electrochemical properties of pristine and treated electrodes. The 600 °C GF has the highest specific capacitance of 34.8 Fg−1 at 100 mV s−1, but the 500 °C GF showed the best battery performance. The good battery performance of the 500 °C GF is attributed to the presence of oxygen functionalities and the absence of thermal degradation during heat treatment. The battery consisting of 500 °C GF electrodes offered the highest voltage efficiency of ~74%, Coulombic efficiency of ~94%, and energy efficiency of ~70% at 20 mA cm−2. Energy efficiency increased by 7% in a battery consisting of heat-treated GF in comparison to pristine GF. The battery is capable of operating for 100 charge–discharge cycles with an average energy efficiency of ~ 67% for over 100 cycles.

Introduction Intracranial atherosclerotic disease (ICAD) is one of the leading causes of ischemic stroke. We sought to identify variables associated with ICAD underlying large vessel occlusion strokes (LVOS) to facilitate pre‐procedural diagnosis. Methods Retrospective analysis of a prospectively collected thrombectomy single comprehensive stroke center database. Inclusion criteria: anterior circulation occlusion involving the intracranial ICA, MCA‐M1/M2/M3 or ACA(A1‐A2‐A3). ICAD cases were matched for age and sex in a 1:1 ratio to non‐ICAD controls. Results A total of 348 patients were included in the analysis. Patients with ICAD more frequently presented with vascular risk factors. ICAD LVOS showed less frequent atrial fibrillation(AF)(4%vs31%,P=0.001), and lower baseline NIHSS(14vs17,P=0.002) compared to the non‐ICAD group. The ICAD group less frequently showed hyperdense vessel sign and territorial cortical infarcts, but presented more frequently borderzone, deep subcortical and bilateral infarcts on CT compared to the non‐ICAD group. ICAD strokes had higher ASPECTS, and more frequently had calcifications at the carotid siphon as well as multifocal intracranial stenosis on CTA. CTA collaterals scores were comparable between groups. The ICAD group had lower median infarct core volume (1vs12 ml;P>0.001), Tmax>4s (249vs276 ml;P>0.003), and Tmax>6s (97vs140 ml;P4:6 s ratio (2vs1;P=0.007) on CTP compared to non‐ICAD group. On multivariable analysis, absence of AF, absence of cortical infarcts, presence calcium at ipsilateral carotid siphon, cerebrovascular stroke risk factors burden (DM‐HTN‐Hyperlipidemia‐smoking), borderzone infarcts either (superficial cortical or Internal deep border zone), and multifocal intracranial stenosis were independent factors associated with ICAD. The model (table 1) by AUC for the whole model had sensitivity of 88% [P=

The growing amount of screen time among adolescents has raised concerns about the effects it may have on their physical and psychological health. Although the literature is divided on whether the effects are mostly positive, neutral, or mostly negative, it is likely that the impacts will be highly individualized with a mixture of good and bad consequences for each person. Understanding behavioral and neurobiological phenomena of adolescence may help to guide research and interventions to optimize the benefits and minimize the risks. Particular aspects of adolescent development relevant to the issue include: (i) hunger for human connectedness; (ii) appetite for adventure; and (iii) desire for data.
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