Search

Detection of ≥50% diameter stenosis left main coronary artery disease (LMD) has prognostic and therapeutic implications. Noninvasive stress imaging or an exercise tolerance test (ETT) are the most common methods to detect obstructive coronary artery disease, though stress test markers of LMD remain ill-defined.The authors sought to identify markers of LMD as detected on coronary computed tomography angiography (CTA), using clinical and stress testing parameters.This was a post hoc analysis of ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), including randomized and nonrandomized participants who had locally determined moderate or severe ischemia on nonimaging ETT, stress nuclear myocardial perfusion imaging, or stress echocardiography followed by CTA to exclude LMD. Stress tests were read by core laboratories. Prior coronary artery bypass grafting was an exclusion. In a stepped multivariate model, the authors identified predictors of LMD, first without and then with stress testing parameters.Among 5,146 participants (mean age 63 years, 74% male), 414 (8%) had LMD. Predictors of LMD were older age (P 0.001), male sex (P 0.01), absence of prior myocardial infarction (P 0.009), transient ischemic dilation of the left ventricle on stress echocardiography (P = 0.05), magnitude of ST-segment depression on ETT (P = 0.004), and peak metabolic equivalents achieved on ETT (P = 0.001). The models were weakly predictive of LMD (C-index 0.643 and 0.684).In patients with moderate or severe ischemia, clinical and stress testing parameters were weakly predictive of LMD on CTA. For most patients with moderate or severe ischemia, anatomical imaging is needed to rule out LMD. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) found that there was no statistical difference in cardiovascular events with an initial invasive strategy as compared with an initial conservative strategy of guideline-directed medical therapy for patients with moderate to severe ischemia on noninvasive testing. In this study, we describe the reasons that potentially eligible patients who were screened for participation in the ISCHEMIA trial did not advance to enrollment, the step prior to randomization. Of those who preliminarily met clinical inclusion criteria on screening logs submitted during the enrollment period, over half did not participate due to physician or patient refusal, a potentially modifiable barrier. This analysis highlights the importance of physician equipoise when advising patients about participation in randomized controlled trials.

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications. Uncontrolled GDM increases the risk of negative pregnancy outcomes for both the pregnant individual and the infant. African Americans (AAs) have higher maternal morbidity and infant mortality rates than non-Hispanic whites (NHWs). The goal of the current study was to examine racial differences in the effect of GDM on birth outcomes. The data from the Pregnancy Risk Assessment Monitoring System (PRAMS) was analyzed with a focus on four states in the southern U.S. (Alabama, Georgia, Louisiana, and Mississippi). The results presented suggest that AAs are at lower risk of GDM than NHW individuals. Even with the lower risk of GDM, AAs are at higher risk of pre-term births. In addition, socioeconomic factors and access to prenatal care play a role in birth outcomes including moderating the effect of GDM on outcomes. A discussion of potential policy interventions that may improve pregnancy outcomes is discussed including increased use of doulas to support pregnant people.

Individualized supportive care is recommended to manage the debilitating effects of advanced prostate cancer and its treatments. Yet, the implementation of supportive care in practice remains inconsistent.The aim of this study was to synthesize the barriers and facilitators to implementing supportive care interventions after identifying supportive care interventions for advanced prostate cancer survivors.PubMed, SCOPUS, CINAHL Complete, ProQuest, and PsycINFO were searched for relevant studies published between 2011 and 2020. Studies were included if they reported on a supportive care intervention and included a description of implementation barriers and/or facilitators. The Theoretical Domains Framework was used to characterize implementation barriers and facilitators.Of the 620 articles identified, 13 met all prespecified inclusion criteria. Primary barriers were related to the domains of environmental context and resources (eg, limited resources), knowledge (eg, insufficient knowledge on efficacy of supportive care), and beliefs about capabilities (eg, lack of confidence in materials). Facilitators fell under environmental context and resources (partnerships with local services), reinforcement (eg, partners inclusion), and skills (eg, delivery by professionals).This scoping review highlights barriers and facilitators that affect supportive care implementation. Future research that focuses on overcoming barriers and maximizing facilitators is needed to improve, modify, or supplement existing supportive care implementation practices.As the number of advanced prostate cancer survivors continues to increase, supportive care must become the standard of care. Future interventions must incorporate increased knowledge and funding, alternative delivery models, and consistent use of specialty nurses.

Cardiovascular risk has traditionally been defined by modifiable and non-modifiable risk factors, such as tobacco use, hyperlipidemia, and family history. However, chemicals and pollutants may also play a role in cardiovascular disease (CVD) risk. Arsenic is a naturally occurring element that is widely distributed in the Earth's crust. Inorganic arsenic (iAs) has been implicated in the pathogenesis of atherosclerosis, with chronic high-dose exposure to iAs ( 100 µg/L) being linked to CVD; however, whether low-to-moderate dose exposures of iAs ( 100 µg/L) are associated with the development of CVD is unclear. Due to limitations of the existing literature, it is difficult to define a threshold for iAs toxicity. Studies demonstrate that the effect of iAs on CVD is far more complex with influences from several factors, including diet, genetics, metabolism, and traditional risk factors such as hypertension and smoking. In this article, we review the existing data of low-to-moderate dose iAs exposure and its effect on CVD, along with highlighting the potential mechanisms of action.

This study aimed to investigate women's adherence patterns to pelvic floor muscle exercises (PFME), their associated factors and within-pattern changes.This was a secondary analysis using data collected from 647 women aged 55 years and older in the USA. Women were randomly assigned to either a 2-h class group or an equivalent content 20-min DVD group to receive PFME complemented with adherence enhancement strategies. Adherence was assessed at 3, 12 and 24 months using three self-reported items matching PFME parameters. TheFour adherence patterns, A, B, C and D, were identified. Women who displayed optimal adherence to all three aforementioned items, i.e. adherence pattern A, constituted 49.1%, 38.2% and 37.2% of women at 3, 12 and 24 months, respectively. Women with income US$100,000 were more likely to display adherence pattern A within 12 months. Of women who had adherence pattern A at 3 months, 63.9% and 49.2% continued in this pattern at 12 and 24 months.Fewer than half of women displayed adherence pattern A for 2 years. Early optimal adherence predicted women's subsequent optimal adherence.

Background: Supportive care interventions can improve quality of life and health outcomes of advanced prostate cancer survivors. Despite the high prevalence of unmet needs, supportive care for this population is sparse. Methods: The databases PubMed, SCOPUS, CINAHL, and ProQuest were searched for relevant articles. Data were extracted, organized by thematic matrix, and categorized according to the seven domains of the Supportive Care Framework for Cancer Care. Results: The search yielded 1678 articles, of which 18 were included in the review and critically appraised. Most studies were cross-sectional with small, non-diverse samples. Supportive care interventions reported for advanced prostate cancer survivors are limited with some positive trends. Most outcomes were symptom-focused and patient self-reported (e.g., anxiety, pain, self-efficacy) evaluated by questionnaires or interview. Interventions delivered in group format reported improvements in more outcomes. Conclusions: Additional supportive care intervention are needed for men with advanced prostate cancer. Because of their crucial position in caring for cancer patients, nurse scientists and clinicians must partner to research and develop patient-centered, culturally relevant supportive care interventions that improve this population’s quality of life and health outcomes. Efforts must concentrate on sampling, domains of needs, theoretical framework, guidelines, and measurement instruments.

Introduction: Perfluoroalkyl substances (PFA)s are ubiquitous synthetic organic compounds used in packaging, flame retardants and stain resistant fabric. The use of older, long-chain, persistent PFAs in the U.S. has been phased out due to cardiometabolic health effects and replaced with short-chain, less persistent, alternative PFAs for which little data on cardiotoxicity exists. We evaluated the relationships between serum PFAs and noninvasive measures of vascular function by carotid-femoral pulse wave velocity (PWV) and brachial artery reactivity testing (BART). Methods: We measured 14 serum PFAs using hybrid solid-phase extraction and ultrahigh-performance liquid chromatography-tandem mass spectrometry in 94 adult outpatients without CVD from an urban medical center. Using medical records and questionnaires, we collected demographic and clinical data; and measured PWV and BART using standard protocols. We assessed associations of individual PFAs with log-transformed BART and PWV using linear regression. We used weighted quantile sum regression to assess effects of correlated PFA mixtures on BART and PWV. Results: Of the 14 measured PFAs, 10 were detectable in >50% of samples, and were included for analysis. Each standard deviation increase in perfluroheptanoic acid (PFHpA) was associated with -0.17 (-0.34, -0.002) decrease in log BART. The weighted index of PFAs in mixture 1 (Table) was significantly and inversely associated with log BART; each tertile increase in the weighted index of mixture 1 was associated with a -0.29 (-0.52, -0.06) decrease in log BART, with PFHpA having the greatest weight (0.73) in the mixture. In contrast, neither individual PFAs nor PFA mixtures were associated with PWV. Conclusions: Increasing concentrations of a new, short-chain PFA, PFHpA, are associated with impaired vascular function among outpatients without CVD. Our findings contribute evidence of potential adverse cardiovascular effects of currently used PFAs.

Introduction: Peripheral artery disease (PAD) and diabetes mellitus (DM) are significant risk factors for atherothrombosis. Platelets mediate atherothrombosis and are therapeutic targets in PAD and DM. We investigated the relationships between PAD, DM, platelet activity, and cardiovascular risk. Methods: The Platelet Activity and Cardiovascular Events (PACE) study enrolled 289 PAD patients undergoing lower extremity revascularization (LER). Prior to LER, platelet activity was measured via light transmission aggregometry in response to submaximal ADP, collagen (coll), serotonin (ser), epinephrine (epi), and arachidonic acid (AA). Patients were followed for a median of 18 months for the composite of major adverse cardiac or limb events (MACLE; MI, stroke, death, major amputation, and limb revascularization). Results: There were 93 (32%) patients with insulin-dependent DM (IDDM), 60 (21%) with non-insulin dependent DM (NIDDM), and 136 (47%) without-DM. Patients with IDDM were more likely than those without DM to be female, non-white, and Hispanic, and to have history of coronary artery disease, heart failure, and critical limb ischemia (PFigure) . MACLE occurred in 51%, 57%, and 69% of the without-DM, NIDDM, and IDDM groups, respectively (P=0.02). Compared to subjects without DM, only those with IDDM were at increased risk of MACLE after multivariable adjustment (aHR 1.6 [95% CI 1.02-2.4]; P=0.04) ( Figure ). After further adjustment for platelet aggregation, the association between IDDM and MACLE was no longer statistically significant (1.4 [0.9-2.3]; P=0.17); platelet aggregation mediated 24% of the excess MACLE risk in individuals with IDDM. Conclusions: In patients with PAD, IDDM is associated with increased platelet activity that mediates, in part, the risk for incident cardiac and limb events.

Introduction: Fine particulate matter air pollution (PM 2.5 ) exposure is associated with elevated circulating inflammatory biomarkers implicated in cardiovascular disease (CVD). Portable Air Cleaners (PAC)s reduce PM 2.5 exposure and may lower concentrations of inflammatory biomarkers. Methods: We performed a systematic review and meta-analysis of randomized crossover trials of in-home high efficiency particulate air (HEPA) PACs vs. sham control on changes in CRP, IL-6, and/or TNFα among adults with no smoking exposure using Medline, Embase, and Cochrane Central Register of Controlled Trials with the Ovid Platform, Inspec, Compendix, and Web of Science Core Collection. Two investigators (S.W, D.W.) independently screened and reviewed the studies. We used RevMan 5.3 to perform the meta-analysis. Results: Search results included 459 articles screened, 26 selected for full review, and 14 that met inclusion criteria, representing N=724 participants included in the meta-analysis. Ten studies reported CRP, 9 reported IL-6, and 5 reported TNFα. Based on WHO guidelines, 5 studies were in regions of extreme PM 2.5 exposure (>35 μg/m 3 ), 3 were high (10-35 μg/m 3 ), 3 were low (3 ), and 2 lacked baseline PM 2.5 . Median (± S.D.) duration of HEPA/sham use was 9 ± 6.6 days. Reductions in PM 2.5 ranged from 2.6 to 54.9 μg/m 3 (35-82%) and varied by baseline PM 2.5 , although reporting of baseline PM 2.5 was incomplete across trials. Compared to sham PAC use, active PACs were associated with a 7% lower CRP (95% CI -13%, 0%) and 12% lower IL-6 (-22%, -2%), P2.5 . Conclusions: Our data demonstrate that PAC use is associated with significant reductions in circulating CRP and IL-6, with a magnitude of effect similar to clinical trials of statins and IL-1β inhibition. Given the role of inflammation in CVD, PACs may be useful to reduce systemic inflammation and cardiovascular risk.

Highly diastereoselective coordination of unsymmetrical cationic 2,2′-bipyridine ligands bearing a chiral amidinium substituent to [Re(CO)3Cl] and [Ir(PhPy)2]+ cores is reported. Binding strength and stereoselectivity have been correlated with the position of the amidinium group on the bipy. The 4-, 5- and 6-substituted ligands all produce C-[Re(CO)3(LH)Cl]X selectively, while only the 4-derivative gives preferred formation of Δ-[Ir(Phpy)2(4-LH)](BF4)2.

Background: Among patients with diabetes and chronic coronary disease, it is unclear if invasive management improves outcomes when added to medical therapy. Methods: The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trials (ie, ISCHEMIA and ISCHEMIA–Chronic Kidney Disease) randomized chronic coronary disease patients to an invasive (medical therapy + angiography and revascularization if feasible) or a conservative approach (medical therapy alone with revascularization if medical therapy failed). Cohorts were combined after no trial-specific effects were observed. Diabetes was defined by history, hemoglobin A1c ≥6.5%, or use of glucose-lowering medication. The primary outcome was all-cause death or myocardial infarction (MI). Heterogeneity of effect of invasive management on death or MI was evaluated using a Bayesian approach to protect against random high or low estimates of treatment effect for patients with versus without diabetes and for diabetes subgroups of clinical (female sex and insulin use) and anatomic features (coronary artery disease severity or left ventricular function). Results: Of 5900 participants with complete baseline data, the median age was 64 years (interquartile range, 57–70), 24% were female, and the median estimated glomerular filtration was 80 mL·min −1 ·1.73 −2 (interquartile range, 64–95). Among the 2553 (43%) of participants with diabetes, the median percent hemoglobin A1c was 7% (interquartile range, 7–8), and 30% were insulin-treated. Participants with diabetes had a 49% increased hazard of death or MI (hazard ratio, 1.49 [95% CI, 1.31–1.70]; P Conclusions: Despite higher risk for death or MI, chronic coronary disease patients with diabetes did not derive incremental benefit from routine invasive management compared with initial medical therapy alone. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01471522.

The quorum sensing signaling systems in Vibrio bacteria converge to control levels of the master transcription factors LuxR/HapR, a family of highly conserved proteins that regulate gene expression for bacterial behaviors. A compound library screen identified 2-thiophenesulfonamide compounds that specifically inhibit Vibrio campbellii LuxR but do not affect cell growth. We synthesized a panel of 50 thiophenesulfonamide compounds to examine the structure-activity relationship effects on Vibrio quorum sensing. The most potent molecule identified, PTSP (3-phenyl-1-(thiophen-2-ylsulfonyl)-1H-pyrazole), inhibits quorum sensing in multiple strains of Vibrio vulnificus, Vibrio parahaemolyticus, and V. campbellii at nanomolar concentrations. However, thiophenesulfonamide inhibition efficacy varies significantly among Vibrio species: PTSP is most inhibitory against V. vulnificus SmcR, but V. cholerae HapR is completely resistant to all thiophenesulfonamides tested. Reverse genetics experiments show that PTSP efficacy is dictated by amino acid sequence in the putative ligand binding pocket: F75Y and C170F SmcR substitutions are each sufficient to eliminate PTSP inhibition. Further, in silico modeling distinguished the most potent thiophenesulfonamides from less effective derivatives. Our results revealed the previously unknown differences in LuxR/HapR proteins that control quorum sensing in Vibrio species and underscore the potential for developing thiophenesulfonamides as specific quorum sensing-directed treatments for Vibrio infections.

ObjectiveThe current study examined the impact of the use of hormonal birth control, cannabis (CB), and alcohol on depression symptoms.Study DesignSurvey data from 3,320 college-aged women collected over a 2-year period. Depression symptoms were assessed using the PHQ-9.ResultsIndividuals taking hormonal birth control (N = 998; age = 19.1 ± 1.6 years) had lower overall depression scores than did those not taking birth control (N = 2,322; age = 19.1 ± 1.8 years) with 15.2% of those not taking hormonal birth control had depressive symptoms while 12.1% of those in the birth control group had depressive symptoms. Additionally, those taking hormonal birth control had higher scores on the alcohol and CB use assessment. A between-subjects ANOVA with depression score as the dependent variable found significant effects hormonal birth control use, CB and alcohol use, as well as a significant interaction between CB use and hormonal birth control use.ConclusionsWhile there are some limitations (e.g., the between subjects design makes it such that there may be uncontrolled differences between groups), the results suggest that hormonal birth control use may help to reduce depressive symptoms.ImplicationsMore studies examining the impact of hormonal birth control and substance use on depression are required. The results suggest a potential interaction between CB and hormonal birth control use on depression symptoms that is not observed for alcohol. This implies that alcohol and CB may be linked to depression via different mechanisms.

Background: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) postulated that patients with stable coronary artery disease (CAD) and moderate or severe ischemia would benefit from revascularization. We investigated the relationship between severity of CAD and ischemia and trial outcomes, overall and by management strategy. Methods: In total, 5179 patients with moderate or severe ischemia were randomized to an initial invasive or conservative management strategy. Blinded, core laboratory–interpreted coronary computed tomographic angiography was used to assess anatomic eligibility for randomization. Extent and severity of CAD were classified with the modified Duke Prognostic Index (n=2475, 48%). Ischemia severity was interpreted by independent core laboratories (nuclear, echocardiography, magnetic resonance imaging, exercise tolerance testing, n=5105, 99%). We compared 4-year event rates across subgroups defined by severity of ischemia and CAD. The primary end point for this analysis was all-cause mortality. Secondary end points were myocardial infarction (MI), cardiovascular death or MI, and the trial primary end point (cardiovascular death, MI, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest). Results: Relative to mild/no ischemia, neither moderate ischemia nor severe ischemia was associated with increased mortality (moderate ischemia hazard ratio [HR], 0.89 [95% CI, 0.61–1.30]; severe ischemia HR, 0.83 [95% CI, 0.57–1.21]; P =0.33). Nonfatal MI rates increased with worsening ischemia severity (HR for moderate ischemia, 1.20 [95% CI, 0.86–1.69] versus mild/no ischemia; HR for severe ischemia, 1.37 [95% CI, 0.98–1.91]; P =0.04 for trend, P =NS after adjustment for CAD). Increasing CAD severity was associated with death (HR, 2.72 [95% CI, 1.06–6.98]) and MI (HR, 3.78 [95% CI, 1.63–8.78]) for the most versus least severe CAD subgroup. Ischemia severity did not identify a subgroup with treatment benefit on mortality, MI, the trial primary end point, or cardiovascular death or MI. In the most severe CAD subgroup (n=659), the 4-year rate of cardiovascular death or MI was lower in the invasive strategy group (difference, 6.3% [95% CI, 0.2%–12.4%]), but 4-year all-cause mortality was similar. Conclusions: Ischemia severity was not associated with increased risk after adjustment for CAD severity. More severe CAD was associated with increased risk. Invasive management did not lower all-cause mortality at 4 years in any ischemia or CAD subgroup. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01471522.

An approach to increasing sensor performance and detection reliability for buried objects is to better understand which physical processes are dominant under certain environmental conditions. The present effort (Phase 2) builds on our previously published prior effort (Phase 1), which examined methods of determining the probability of detection and false alarm rates using thermal infrared for buried-object detection. The study utilized a 3.05 × 3.05 m test plot in Hanover, New Hampshire. Unlike Phase 1, the current effort involved removing the soil from the test plot area, homogenizing the material, then reapplying it into eight discrete layers along with buried sensors and objects representing targets of inter-est. Each layer was compacted to a uniform density consistent with the background undisturbed density. Homogenization greatly reduced the microscale soil temperature variability, simplifying data analysis. The Phase 2 study spanned May–November 2018. Simultaneous measurements of soil temperature and moisture (as well as air temperature and humidity, cloud cover, and incoming solar radiation) were obtained daily and recorded at 15-minute intervals and coupled with thermal infrared and electro-optical image collection at 5-minute intervals.

Objectives Inaccuracies in cause-of-death information in death certificates can reduce the validity of national death statistics and result in poor targeting of resources to reduce morbidity and mortality in people with HIV. Our objective was to measure the sensitivity, specificity, and agreement between multiple causes of deaths from death certificates obtained from the National Death Index (NDI) and causes determined by expert physician review. Methods Physician specialists determined the cause of death using information collected from the medical records of 50 randomly selected HIV-infected people who died in San Francisco from July 1, 2016, through May 31, 2017. Using expert review as the gold standard, we measured sensitivity, specificity, and agreement. Results The NDI had a sensitivity of 53.9% and a specificity of 66.7% for HIV deaths. The NDI had a moderate sensitivity for non–AIDS-related infectious diseases and non–AIDS-related cancers (70.6% and 75.0%, respectively) and high specificity for these causes (100.0% and 94.7%, respectively). The NDI had low sensitivity and high specificity for substance abuse (27.3% and 100.0%, respectively), heart disease (58.3% and 86.8%, respectively), hepatitis B/C (33.3% and 97.7%, respectively), and mental illness (50.0% and 97.8%, respectively). The measure of agreement between expert review and the NDI was lowest for HIV (κ = 0.20); moderate for heart disease (κ = 0.45) and hepatitis B/C (κ = 0.40); high for non–AIDS-related infectious diseases (κ = 0.76) and non–AIDS-related cancers (κ = 0.72); and low for all other causes of death (κ < 0.35). Conclusions Our findings support education and training of health care providers to improve the accuracy of cause-of-death information on death certificates.

Contact sports affect measures at multiple scales such as transcriptomics, metabolomics, brain function, and behavior, but studies have not yet studied the statistical structure of how they are integrated. This preliminary study, examining collegiate American football players, integrated across-season changes (Δ) from transcriptomic and metabolomic variables (neuroinflammatory miRNAs and metabolites), neuroimaging (resting-state fMRI network fingerprint similarity), and virtual reality (VR)-based motor control. These findings were then assessed against head acceleration events (HAE). Using permutation-based moderation analysis (all p F p e r m , p β 3 p e r m ≤ 0.05 ) , we observed that (1) Δtridecenedioate, a mono-unsaturated fatty acid, interacted with ΔmiR-505 to predict default mode network (DMN) fingerprint similarity, meaning the interaction between two molecular biology measures predicted a neuroimaging measure. Further, (2) Δtridecenedioate and DMN fingerprint similarity interacted to predict motor control, indicating the interaction of a molecular and a neuroimaging measure predicted behavior. ΔmiR-505 was positively related to HAE and DMN fingerprint similarity was negatively related to HAE and reduced relative to non-athlete subjects. These multi-scale, moderating relationships between a potential ROS scavenger, neuroinflammatory miRNA, reduced brain connectivity, and diminished motor control argue that seemingly healthy athletes with frequent HAE may experience chronic neuroinflammation. This imaging-omics framework using permutation-based mediation/moderation analysis has general applicability for human-animal translational studies.

SLC4 transporters play significant roles in pH regulation and cellular sodium transport. The previously solved structures of the outward facing (OF) conformation for AE1 (SLC4A1) and NBCe1 (SLC4A4) transporters revealed an identical overall fold despite their different transport modes (chloride/bicarbonate exchange versus sodium-carbonate cotransport). However, the exact mechanism determining the different transport modes in the SLC4 family remains unknown. In this work, we report the cryo-EM 3.4 Å structure of the OF conformation of NDCBE (SLC4A8), which shares transport properties with both AE1 and NBCe1 by mediating the electroneutral exchange of sodium-carbonate with chloride. This structure features a fully resolved extracellular loop 3 and well-defined densities corresponding to sodium and carbonate ions in the tentative substrate binding pocket. Further, we combine computational modeling with functional studies to unravel the molecular determinants involved in NDCBE and SLC4 transport., The mechanisms involved in SLC4-mediated ion transport are still under debate. Here, the authors present a cryoEM structure of the Sodium-driven Chloride/Bicarbonate Exchanger NDCBE, which - together with computational modeling and mutagenesis - reveals molecular determinants of ion transport by SLC4.

A new cardiometabolic-based chronic disease (CMBCD) model is presented that provides a basis for early and sustainable, evidence-based therapeutic targeting to promote cardiometabolic health and mitigate the development and ravages of cardiovascular disease. In the first part of this JACC State-of-the-Art Review, a framework is presented for CMBCD, focusing on 3 primary drivers (genetics, environment, and behavior) and 2 metabolic drivers (adiposity and dysglycemia) with applications to 3 cardiovascular endpoints (coronary heart disease, heart failure, and atrial fibrillation). Specific mechanistic pathways are presented configuring early primary drivers with subsequent adiposity, insulin resistance, β-cell dysfunction, and metabolic syndrome, leading to cardiovascular disease. The context for building this CMBCD model is to expose actionable targets for prevention to achieve optimal cardiovascular outcomes. The tactical implementation of this CMBCD model is the subject of second part of this JACC State-of-the-Art Review.

The ability of alkali metal complexes featuring functionalized BINOL-derived ligands to catalyze ketone hydroboration reactions was explored. The reduced products were formed in excellent yields and with variable enantioselectivities dependent upon the nature of the ligand and the alkali metal cation.

Understanding the impact of concussion history on mental health—mood disorders and substance use—is an essential step in characterizing the psychological and behavioral consequences of concussion and in developing effective treatments. The objective of this study was to examine the association between the history of concussion and substance abuse by investigating both its direct and indirect association via mood disorder. A secondary objective was to determine whether gender moderates the association. A comprehensive survey was administered to 4849 college-age adults that assessed history of concussion; depression, anxiety, and panic disorders using the Patient Health Questionnaire (PHQ); and substance use using the Alcohol Use Disorders Identification Test (AUDIT) (alcohol) and Cannabis Use Disorders Identification Test-Revised (CUDIT) (cannabis). Regression models were used to examine the association between concussion history and substance use. Mood disorders were entered into the model as mediators and gender as a moderator variable. Those with a history of concussion had higher panic, AUDIT, and CUDIT scores than those with no history of concussion, and AUDIT and CUDIT scores showed an interaction between concussion history and gender. The regression models revealed significant direct and indirect (via depression and panic disorder) effects of concussion history on alcohol and cannabis use, which was moderated by gender. Concussion can have long-term psychological consequences and appears to affect both mood and substance use. The results presented demonstrate that the relationship between concussion and substance use is complex with mood disorder mediating the effect.