Relationship of apolipoprotein C-III proteoform composition with ankle-brachial index and peripheral artery disease in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Apolipoprotein C-III (apoC-III) proteoform composition shows distinct relationships with plasma lipids and cardiovascular risk. The present study tested whether apoC-III proteoforms are associated with risk of peripheral artery disease (PAD). METHODS: ApoC-III proteoforms, i.e., native (C-III0a), and glycosylated with zero (C-III0b), one (C-III1) or two (C-III2) sialic acids, were measured by mass spectrometry immunoassay on 5,734 Multi-Ethnic Study of Atherosclerosis participants who were subsequently followed for clinical PAD over 17 years. Ankle-brachial index (ABI) was also assessed at baseline and then 3 and 10 years later in 4,830 participants. RESULTS: Higher baseline C-III0b/C-III1 and lower baseline C-III2/C-III1 were associated with slower decline in ABI (follow-up adjusted for baseline) over time, independently of cardiometabolic risk factors, and plasma triglycerides and HDL cholesterol levels (estimated difference per 1 SD was 0.31 % for both, p < 0.01). The associations between C-III2/C-III1 and changes in ABI were stronger in men (-1.21 % vs. -0.27 % in women), and in Black and Chinese participants (-0.83 % and -0.86 % vs. 0.12 % in White). Higher C-III0b/C-III1 was associated with a trend for lower risk of PAD (HR = 0.84 [95%CI: 0.67-1.04]) that became stronger after excluding participants on lipid-lowering medications (0.73 [95%CI: 0.57-0.94]). Neither change in ABI nor clinical PAD was related to total apoC-III levels. CONCLUSIONS: We found associations of apoC-III proteoform composition with changes in ABI that were independent of other risk factors, including plasma lipids. Our data further support unique properties of apoC-III proteoforms in modulating vascular health that go beyond total apoC-III levels.

The prospective relationship between a-priori intentions for and patterns of e-cigarette use among adults who smoke cigarettes.

BACKGROUND: Electronic (e-)cigarettes may help adult cigarette smokers achieve cigarette cessation, depending on patterns of e-cigarette use. Among cigarette smokers who do not use e-cigarettes, it is unclear if and how a-priori intentions for use are related to uptake patterns. Longitudinal studies have focused on established e-cigarette users or adolescent and young adult populations exclusively. METHODS: Within a nationwide randomized clinical trial (N = 638), adult cigarette smokers not currently using e-cigarettes were randomized (2:1) to receive (or not) one-month sampling of e-cigarettes. An exploratory factor analysis (EFA) was performed on an established 15-item measure assessing a-priori intentions for e-cigarette use to identify latent variables. Among those receiving e-cigarette products, regression models examined relationships between intentions and: 1) uptake (yes/no), 2) frequency (number of days per week), and 3) amount (puffing episodes per day) of e-cigarette use at one-month follow-up. RESULTS: Two factors emerged from the EFA: 1) cigarette-related intentions (e.g., cigarette cessation, no smell) and 2) novel appeal of e-cigarettes (e.g., flavors). Three items remained and were treated as separate intentions: "feels like cigarette smoking", "curiosity", and "affordability". In the final multivariable models, "feel like cigarette smoking" predicted more frequent e-cigarette use (ß = 0.187, SE = 0.086, p = 0.03); however, none of the five factors/intentions were significantly associated with uptake or amount of use. CONCLUSIONS: For adult cigarette smokers not currently using e-cigarettes, a-priori intentions for using e-cigarettes might not be predictive of if or how these products will be used in the future, suggesting that motives may not drive use behavior.

Velocity-Load Jump Testing Predicts Acceleration Performance in Elite Speed Skaters: But Does Movement Specificity Matter?

PURPOSE: In this study, we compared the influence of movement specificity during velocity-load jump testing to predict on-ice acceleration performance in elite speed skaters. METHODS: Elite long-track speed skaters (N = 27) performed velocity-load testing with 3 external loads during unilateral horizontal jumping, lateral jumping, and bilateral vertical countermovement jumping. For the unilateral tests, external load conditions were set to 10 N, 7.5% and 15% of external load relative to body weight. For the countermovement jumping, load conditions were body weight and 30% and 60% of external load relative to body weight. On-ice performance measures were obtained during maximal 50-m accelerations from a standing start, including maximal skating speed, maximal acceleration capacity, and maximum horizontal power. The 100-m split time from a 500-m race was also obtained. Regularized regression models were used to identify the most important predictors of on-ice acceleration performance. In addition to regularized regression coefficients, Pearson correlation coefficients (r) were calculated for all variables retained by the model to assess interrelationships between single predictors and on-ice performance measures. RESULTS: The countermovement jump with 30% of body mass demonstrated the strongest association with maximal skating speed, maximum horizontal power, and 100-m time (regularized regression coefficient = .16-.49, r = .84-.97, P < .001). Horizontal jump with 15% of body mass was the strongest predictor of maximal acceleration capacity performance (regularized regression coefficient = .08, r = .83, P < .001). CONCLUSIONS: The findings of this study suggest that mechanical specificity rather than movement specificity was more relevant for predicting on-ice acceleration performance.

Ice formation and its elimination in cryopreservation of oocytes.

Damage from ice and toxicity of ice-inhibiting cryoprotective agents (CPAs) are key issues in assisted reproduction of humans, domestic animals, and endangered species using cryopreserved oocytes and embryos. Ice formed in bovine oocytes (similar in size to oocytes of humans and most other mammals) after rapid cooling and during rapid warming were examined using synchrotron-based time-resolved x-ray diffraction. Using cooling rates, warming rates and CPA concentrations of current practice, oocytes show no ice after cooling but always develop large ice fractions - consistent with crystallization of most free water - during warming, so most ice-related damage must occur during warming. Increasing cooling rates allows oocytes soaked as in current practice to remain essentially ice free during both cooling and warming. Much larger convective warming rates are demonstrated and will allow routine ice-free cryopreservation with smaller CPA concentrations. These results clarify the roles of cooling, warming, and CPA concentration in generating ice in oocytes and establish the structure and grain size of ice formed. Ice formation can be eliminated as a factor affecting post-thaw oocyte viability and development in many species, improving outcomes and allowing other deleterious effects of the cryopreservation cycle to be independently studied.

Let-7 restrains an oncogenic epigenetic circuit in AT2 cells to prevent ectopic formation of fibrogenic transitional cell intermediates and pulmonary fibrosis.

Analysis of lung alveolar type 2 (AT2) progenitor stem cells has highlighted fundamental mechanisms that direct their differentiation into alveolar type 1 cells (AT1s) in lung repair and disease. However, microRNA (miRNA) mediated post-transcriptional mechanisms which govern this nexus remain understudied. We show here that the let-7 miRNA family serves a homeostatic role in governance of AT2 quiescence, specifically by preventing the uncontrolled accumulation of AT2 transitional cells and by promoting AT1 differentiation to safeguard the lung from spontaneous alveolar destruction and fibrosis. Using mice and organoid models with genetic ablation of let-7a1/let-7f1/let-7d cluster ( let-7afd ) in AT2 cells, we demonstrate prevents AT1 differentiation and results in aberrant accumulation of AT2 transitional cells in progressive pulmonary fibrosis. Integration of enhanced AGO2 UV-crosslinking and immunoprecipitation sequencing (AGO2-eCLIP) with RNA-sequencing from AT2 cells uncovered the induction of direct targets of let-7 in an oncogene feed-forward regulatory network including BACH1/EZH2 which drives an aberrant fibrotic cascade. Additional analyses by CUT&RUN-sequencing revealed loss of let-7afd hampers AT1 differentiation by eliciting aberrant histone EZH2 methylation which prevents the exit of AT2 transitional cells into terminal AT1s. This study identifies let-7 as a key gatekeeper of post-transcriptional and epigenetic chromatin signals to prevent AT2-driven pulmonary fibrosis.

ACR Appropriateness Criteria® Management of Uterine Fibroids: 2023 Update.

Uterine fibroids are the most common benign tumor in women of reproductive age and can present with symptoms including bleeding, bulk related symptoms, and infertility. Several treatment options are available for the management of uterine fibroids, including medical management, minimally invasive therapies such as uterine artery embolization and MR-guided focused ultrasound ablation, and surgical interventions ranging from laparoscopic myomectomy to open hysterectomy. Given this wide range of therapeutic interventions, it is important to understand the data supporting these interventions and to be able to apply it in different clinical settings. This document provides a summary of recent trials supporting various therapies for uterine fibroids, including recent evidence for MR-guided focused ultrasound ablation and a detailed discussion of fertility outcomes in myomectomy and uterine fibroid embolization. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

ACR Appropriateness Criteria® Cerebrovascular Diseases-Stroke and Stroke-Related Conditions.

Cerebrovascular disease encompasses a vast array of conditions. The imaging recommendations for stroke-related conditions involving noninflammatory steno-occlusive arterial and venous cerebrovascular disease including carotid stenosis, carotid dissection, intracranial large vessel occlusion, and cerebral venous sinus thrombosis are encompassed by this document. Additional imaging recommendations regarding complications of these conditions including intraparenchymal hemorrhage and completed ischemic strokes are also discussed. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Adjunctive Statistical Standardization of Adjuvant Estrogen Receptor and Progesterone Receptor in Canadian Cancer Trials Group MA.27 Postmenopausal Breast Cancer Trial of Exemestane Versus Anastrozole.

PURPOSE: ASCO/College of American Pathologists guidelines recommend reporting estrogen receptor (ER) and progesterone receptor (PgR) as positive with (1%-100%) staining. Statistically standardized quantitated positivity could indicate differential associations of positivity with breast cancer outcomes. METHODS: MA.27 (ClinicalTrials.gov identifier: NCT00066573) was a phase III adjuvant trial of exemestane versus anastrozole in postmenopausal women with early-stage breast cancer. Immunochemistry ER and PgR HSCORE and % positivity (%+) were centrally assessed by machine image quantitation and statistically standardized to mean 0 and standard deviation (SD) 1 after Box-Cox variance stabilization transformations of square for ER; for PgR, (1) natural logarithm (0.1 added to 0 HSCOREs and 0%+) and (2) square root. Our primary end point was MA.27 distant disease-free survival (DDFS) at a median 4.1-year follow-up, and secondary end point was event-free survival (EFS). Univariate survival with cut points at SDs about a mean of 0 (≤-1; (-1, 0]; (0, 1]; >1) was described with Kaplan-Meier plots and examined with Wilcoxon (Peto-Prentice) test statistic. Adjusted Cox multivariable regressions had two-sided Wald tests and nominal significance P < .05. RESULTS: Of 7,576 women accrued, 3,048 women's tumors had machine-quantitated image analysis results: 2,900 (95%) for ER, 2,726 (89%) for PgR, and 2,582 (85% of 3,048) with both ER and PgR. Higher statistically standardized ER and PgR HSCORE and %+ were associated with better univariate DDFS and EFS (P < .001). In multivariable assessments, ER HSCORE and %+ were not significantly associated (P = .52-.88) with DDFS in models with PgR, whereas higher PgR HSCORE and %+ were significantly associated with better DDFS (P = .001) in models with ER. CONCLUSION: Adjunctive statistical standardization differentiated quantitated levels of ER and PgR. Patients with higher ER- and PgR-standardized units had superior DDFS compared with those with HSCOREs and %+ ≤-1.

Spatiotemporal assessment of pathogenic Leptospira in subtropical coastal watersheds.

The World Health Organization classifies leptospirosis as a significant public health concern, predominantly affecting impoverished and unsanitary regions. By using the Pensacola Bay System as a case study, this study examines the underappreciated susceptibility of developed subtropical coastal ecosystems such as the Pensacola Bay System to neglected zoonotic pathogens such as Leptospira. We analyzed 132 water samples collected over 12 months from 44 distinct locations with high levels of Escherichia coli (>410 most probable number/100 mL). Fecal indicator bacteria (FIB) concentrations were assessed using IDEXX Colilert-18 and Enterolert-18, and an analysis of water physiochemical characteristics and rainfall intensity was conducted. The LipL32 gene was used as a quantitative polymerase chain reaction (qPCR) indicator to identify the distribution of Leptospira interrogans. The results revealed 12 instances of the presence of L. interrogans at sites with high FIB over various land cover and aquatic ecosystem types. Independent of specific rainfall events, a seasonal relationship between precipitation and elevated rates of fecal bacteria and leptospirosis was found. These findings highlight qPCR's utility in identifying pathogens in aquatic environments and the widespread conditions where it can be found in natural and developed areas.

Association between Blood Pressure Levels and Premature Atrial Contractions in Patients with Hypertension.

BACKGROUND: High blood pressure (BP) induces left atrial structural and functional remodeling that increases susceptibility to atrial arrhythmia. We hypothesized that lower systolic BP (SBP) levels are associated with a lower prevalence of premature atrial contractions (PACs) in patients with hypertension. METHODS: This analysis included 4,697 participants (mean age 62±13.1 years, 50% women, 25.6% blacks) with hypertension from the Third National Health and Nutrition Examination Survey who did not have a prior history of cardiovascular disease (CVD). Multivariable logistic regression was used to examine the cross-sectional association between SBP and prevalence of PACs ascertained from 12-lead resting electrocardiograms. Multivariable Cox proportional hazard analysis was used to examine the association between baseline PACs and CVD mortality. RESULTS: Approximately 1.6% (n=74) of participants had baseline PACs. Patients with SBP ≤140 mmHg had a lower prevalence of PACs than those with SBP ≥140 mmHg (1.1% vs. 1.9%, p-value=0.01). In a multivariable logistic regression model, each 10 mmHg decrease in SBP was associated with a 12% lower odds of PACs (OR (95%CI): 0.88 (0.77-0.99)). During 14 years of follow-up, 645 CVD deaths occurred. In a multivariable-adjusted Cox model, presence of PACs was associated with a 78% increased risk of CVD mortality (HR (95%CI): 1.78 (1.23-2.60)). CONCLUSIONS: In patients with hypertension, lower SBP levels are associated with a lower prevalence of PACs, and presence of PACs is associated with a higher risk of CVD mortality risk. These findings highlight the potential role of BP lowering in the management of cardiac arrhythmias.

Peripheral expression of brain-penetrant progranulin rescues pathologies in mouse models of frontotemporal lobar degeneration.

Progranulin (PGRN) haploinsufficiency is a major risk factor for frontotemporal lobar degeneration with TAR DNA-binding protein 43 (TDP-43) pathology (FTLD-GRN). Multiple therapeutic strategies are in clinical development to restore PGRN in the CNS, including gene therapy. However, a limitation of current gene therapy approaches aimed to alleviate FTLD-associated pathologies may be their inefficient brain exposure and biodistribution. We therefore developed an adeno-associated virus (AAV) targeting the liver (L) to achieve sustained peripheral expression of a transferrin receptor (TfR) binding, brain-penetrant (b) PGRN variant [AAV(L):bPGRN] in two mouse models of FTLD-GRN, namely, Grn knockout and GrnxTmem106b double knockout mice. This therapeutic strategy avoids potential safety and biodistribution issues of CNS-administered AAVs and maintains sustained concentrations of PGRN in the brain after a single dose. AAV(L):bPGRN treatment reduced several FTLD-GRN-associated pathologies including severe motor function deficits, aberrant TDP-43 phosphorylation, dysfunctional protein degradation, lipid metabolism, gliosis, and neurodegeneration in the brain. The potential translatability of our findings was tested in an in vitro model using cocultured human induced pluripotent stem cell (hiPSC)-derived microglia lacking PGRN and TMEM106B and wild-type hiPSC-derived neurons. As in mice, aberrant TDP-43, lysosomal dysfunction, and neuronal loss were ameliorated after treatment with exogenous TfR-binding protein transport vehicle fused to PGRN (PTV:PGRN). Together, our studies suggest that peripherally administered brain-penetrant PGRN replacement strategies ameliorate FTLD-GRN relevant phenotypes including TDP-43 pathology, neurodegeneration, and behavioral deficits. Our data provide preclinical proof of concept for the use of this AAV platform for treatment of FTLD-GRN and potentially other CNS disorders.

A Preoperative Risk Assessment Tool for Predicting Adverse Outcomes among Total Shoulder Arthroplasty Patients.

BACKGROUND: With the increased utilization of Total Shoulder Arthroplasty (TSA) in the outpatient setting, understanding the risk factors associated with complications and hospital readmissions becomes a more significant consideration. Prior developed assessment metrics in the literature either consisted of hard-to-implement tools or relied on postoperative data to guide decision-making. This study aimed to develop a preoperative risk assessment tool to help predict the risk of hospital readmission and other postoperative adverse outcomes. METHODS: We retrospectively evaluated the 2019-2022(Q2) Medicare fee-for-service inpatient and outpatient claims data to identify primary anatomic or reserve TSAs and to predict postoperative adverse outcomes within 90 days post-discharge, including all-cause hospital readmissions, postoperative complications, emergency room visits, and mortality. We screened 108 candidate predictors, including demographics, social determinants of health, TSA indications, prior 12-month hospital and skilled nursing home admissions, comorbidities measured by hierarchical conditional categories, and prior orthopedic device-related complications. We used two approaches to reduce the number of predictors based on 80% of the data: 1) the Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression and 2) the machine-learning-based cross-validation approach, with the resulting predictor sets being assessed in the remaining 20% of the data. A scoring system was created based on the final regression models' coefficients, and score cutoff points were determined for low, medium, and high-risk patients. RESULTS: A total of 208,634 TSA cases were included. There was a 6.8% hospital readmission rate with 11.2% of cases having at least one postoperative adverse outcome. Fifteen covariates were identified for predicting hospital readmission with the area under the curve (AUC) of 0.70, and 16 were selected to predict any adverse postoperative outcome (AUC=0.75). The LASSO and machine learning approaches had similar performance. Advanced age and a history of fracture due to orthopedic devices are among the top predictors of hospital readmissions and other adverse outcomes. The score range for hospital readmission and an adverse postoperative outcome was 0 to 48 and 0 to 79, respectively. The cutoff points for the low, medium, and high-risk categories are 0-9, 10-14, ≥15 for hospital readmissions, and 0-11, 12-16, ≥17 for the composite outcome. CONCLUSION: Based on Medicare fee-for-service claims data, this study presents a preoperative risk stratification tool to assess hospital readmission or adverse surgical outcomes following TSA. Further investigation is warranted to validate these tools in a variety of diverse demographic settings and improve their predictive performance.

Loneliness and sleep in everyday life: Using ecological momentary assessment to characterize the shape of daily loneliness experience.

BACKGROUND: Loneliness has been linked to an increased risk of sleep problems. Past research has largely relied on trait loneliness or daily recall loneliness when evaluating associations with sleep. OBJECTIVE: The present study extended this work by evaluating the patterns of loneliness throughout the day, including a daily average of all reports, a maximum value, and daily variation. These loneliness patterns predicted daily subjective and objective sleep measures to evaluate whether they provide unique insight to this relationship. METHODS: Undergraduate students (n = 71; 77% female; age 18-28) completed 2weeks of electronic surveys 4 times a day to assess loneliness. Each morning participants completed a diary of their prior night's sleep quality, as well as wore actigraphy devices to objectively assess sleep parameters. A total of 778 momentary surveys and 565days of actigraphy-assessed sleep data were collected. Multilevel models tested whether within-person daily aggregates of loneliness were associated with within-person daily sleep outcome variables. RESULTS: Subjective sleep duration, quality, and fatigue were significantly predicted by daily average loneliness. Subjective sleep latency, quality, and fatigue were significantly predicted by daily max loneliness. Only fatigue was significantly predicted by daily loneliness variability. No objective sleep measures were significantly predicted by daily loneliness measures. CONCLUSIONS: Patterns of daily loneliness focusing on central tendency (average) or intensity (max) were more consistently associated with subjective (but not objective) assessments of sleep than variability.

The origins of unpredictability in life outcome prediction tasks.

Why are some life outcomes difficult to predict? We investigated this question through in-depth qualitative interviews with 40 families sampled from a multidecade longitudinal study. Our sampling and interviewing process was informed by the earlier efforts of hundreds of researchers to predict life outcomes for participants in this study. The qualitative evidence we uncovered in these interviews combined with a mathematical decomposition of prediction error led us to create a conceptual framework. Our specific evidence and our more general framework suggest that unpredictability should be expected in many life outcome prediction tasks, even in the presence of complex algorithms and large datasets. Our work provides a foundation for future empirical and theoretical work on unpredictability in human lives.

Social Justice Education in CAATE-Accredited Post-Baccalaureate Athletic Training Programs.

Social justice education (SJE) prepares clinicians to provide patient-centered care. Our purpose was to assess SJE in CAATE-accredited, post-baccalaureate professional athletic training programs. We used a cross-sectional, online survey. Individuals (n=215) in their last year of post-baccalaureate professional education or those who were within 6 months post-graduation participated. The survey included closed and open-ended questions regarding types of education, topics of education, perceived confidence, and levels of agreement regarding identifying, addressing, and applying social justice concepts. Students from different cultural ethnicities reported having different educational experiences relative to their formal and informal instruction. Significant differences were identified between cultural ethnicity groups on perceptions of professors' knowledge (p<0.001), preceptors' knowledge (p<0.001), and agreement their program prepared them to address social justice issues (p<0.001). Two domains emerged from the open-ended responses: 1) social justice defined and 2) educational needs. Participants described social justice as equality, equity, and justice for minoritized people. Participants described SJE as not occurring or limited, and they expressed a desire for active practical experiences from heterogeneous and unbiased sources. As programs move to incorporate CAATE standards, more frequent and varied SJE is expected from minoritized students.

Temporal trends in disparities in COVID-19 seropositivity among Canadian blood donors.

BACKGROUND: In Canada's largest COVID-19 serological study, SARS-CoV-2 antibodies in blood donors have been monitored since 2020. No study has analysed changes in the association between anti-N seropositivity (a marker of recent infection) and geographic and sociodemographic characteristics over the pandemic. METHODS: Using Bayesian multi-level models with spatial effects at the census division level, we analysed changes in correlates of SARS-CoV-2 anti-N seropositivity across three periods in which different variants predominated (pre-Delta, Delta and Omicron). We analysed disparities by geographic area, individual traits (age, sex, race) and neighbourhood factors (urbanicity, material deprivation and social deprivation). Data were from 420 319 blood donations across four regions (Ontario, British Columbia [BC], the Prairies and the Atlantic region) from December 2020 to November 2022. RESULTS: Seropositivity was higher for racialized minorities, males and individuals in more materially deprived neighbourhoods in the pre-Delta and Delta waves. These subgroup differences dissipated in the Omicron wave as large swaths of the population became infected. Across all waves, seropositivity was higher in younger individuals and those with lower neighbourhood social deprivation. Rural residents had high seropositivity in the Prairies, but not other regions. Compared to generalized linear models, multi-level models with spatial effects had better fit and lower error when predicting SARS-CoV-2 anti-N seropositivity by geographic region. CONCLUSIONS: Correlates of recent COVID-19 infection have evolved over the pandemic. Many disparities lessened during the Omicron wave, but public health intervention may be warranted to address persistently higher burden among young people and those with less social deprivation.

Coronary circulation enhances the aerobic performance of wild Pacific salmon.

Female Pacific salmon often experience higher mortality than males during their once-in-a-lifetime up-river spawning migration, particularly when exposed to secondary stressors (e.g. high temperatures). However, the underlying mechanisms remain unknown. One hypothesis is that female Pacific salmon hearts are more oxygen-limited than males and are less able to supply oxygen to the body's tissues during this demanding migration. Notably, female hearts have higher coronary blood flow, which could indicate a greater reliance on this oxygen source. Oxygen limitations can develop from naturally occurring coronary blockages (i.e., coronary arteriosclerosis) found in mature salmon hearts. If female hearts rely more heavily on coronary blood flow but experience similar arteriosclerosis levels as males, they will have disproportionately impaired aerobic performance. To test this hypothesis, we measured resting (RMR) and maximum metabolic rate (MMR), aerobic scope (AS) and acute upper thermal tolerance in coho salmon (Oncorhynchus kisutch) with an intact or artificially blocked coronary oxygen supply. We also assessed venous blood oxygen and chemistry (cortisol, ions, and metabolite concentrations) at different time intervals during recovery from exhaustive exercise. We found that coronary blockage impaired MMR, AS, and the partial pressure of oxygen in venous blood (PvO2) during exercise recovery but did not differ between sexes. Coronary ligation lowered acute upper thermal tolerance by 1.1°C. Though we did not find evidence of enhanced female reliance on coronary supply, our findings highlight the importance of coronary blood supply for mature wild salmon, where migration success may be linked to cardiac performance, particularly during warm water conditions.

Revealing the Existence of Long-Range Liquid-Liquid Interfacial Potential in Phase-Transfer Processes.

By employing fluorescence wide-field microscopy and a nanoparticle-based phase transfer catalyst (PTC), consisting of a fluorescent silica nanoparticle functionalized with trioctylpropylammonium bromide, we demonstrate that in the presence of NaOH, single nanoparticles display subdiffusive motion along the axis normal to an aqueous liquid-organic liquid interface. This is because of an extended interfacial potential with a shallow well (∼1 kBT) that stretches a few µm into the organic phase, in contrast to previous molecular dynamics studies that reported narrow interfaces on the order of ∼1 nm. Spontaneous interfacial emulsification induced by NaOH results in the propagation of water-in-oil nanoemulsions into the organic solvent that creates an equilibrium hybrid-solvent composition that solvates the PTC. A greater mobility and longer residence time of the PTC at the potential well enhance the interfacial phase transfer process and catalytic efficiency.

Formulary Coverage of Brand-Name Adalimumab and Biosimilars Across Medicare Part D Plans.

This study examines formulary coverage of brand-name adalimumab and biosimilars across Medicare Part D plans.

A Geospatial Analysis of Barriers to Cleft Lip and Palate Care in the United States.

OBJECTIVE: This study evaluates the geospatial distribution of cleft lip and/or cleft palate (CL/P) care in the United States, assesses disparities between families with and without one-hour proximity to CL/P care, and recommends interventions for improving access. DESIGN: We identified American Cleft Palate Craniofacial Association-approved CL/P teams and calculated a one-hour driving radius around each clinic. We then used census data to compare risk factors for developing cleft (i.e., incidence risk factors) and obstacles to care (i.e., access risk factors) between counties with and without one-hour proximity. RESULTS: We identified 187 CL/P teams in 45 states. Most were in the South (n = 60, 32.0%), though children in the Middle Atlantic had the greatest access to care. Alabama, Mississippi, Tennessee, and Kentucky had the least access. Children without access were 39% more likely to have gestational tobacco exposure, 8% more likely to have gestational obesity exposure, and 28% less likely to have health insurance (p < 0.01). Children without access in the South were 29% more likely to have a low birth weight and 46% more likely to be living below the poverty line (p < 0.01). Children with access were twice as likely to live in immigrant families and 7-times more likely to speak English as a second language. CONCLUSIONS: Pronounced disparities affect patients with and without one-hour access to CL/P care. Interventions should address care costs for patients living furthest without access and language barriers for patients with access that speak English as a second language.