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There are controversies regarding the impact of sex on mortality and postoperative complications in patients undergoing on-pump coronary artery bypass grafting (CABG), although some studies demonstrate comparable outcomes. This study sought to evaluate sex differences regarding risk factors associated with hospital mortality and postoperative clinical outcomes among patients undergoing isolated on-pump CABG. We conducted a retrospective observational cohort study of patients who underwent isolated on-pump CABG from January 1996 to January 2020. Patients were divided into two groups (male and female) and compared regarding preoperative characteristics, surgical technical variables, and in-hospital outcomes. All-cause mortality between groups was compared using logistic regression. Risk factors for mortality, along with their respective odds ratios (OR), were separately assessed using a logistic regression model with p-values for interaction. We analyzed 4,882 patients, of whom 31.6% were female. Women exhibited a higher prevalence of age >75 years (12.2% vs 8.3%, p<0.001), obesity (22.6% vs 11.5%, p<0.001), diabetes (41.6% vs 32.2%, p<0.001), hypertension (85.2% vs 73.5%, p<0.001), and NYHA functional classes 3 and 4 (16.2% vs 11.2%, p<0.001) compared to men. Use of the mammary artery for revascularization was less frequent among women (73.8% vs 79.9%, p<0.001), who also received fewer saphenous vein grafts (2.17 vs 2.27, p = 0.002). A history of previous or recent myocardial infarction (MI) had an impact on women's mortality, unlike in men (OR 1.61 vs 0.94, p = 0.014; OR 1.86 vs 0.99, p = 0.015, respectively). After adjusting for several risk factors, mortality was found to be comparable between men and women, with an OR of 1.20 (95% CI 0.94-1.53, p = 0.129). In conclusion, female patients undergoing isolated on-pump CABG presented with a higher number of comorbidities. Previous and recent MI were associated with higher mortality only in women. In this cohort analysis, female gender was not identified as an independent risk factor for outcome after CABG., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ferreira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: Conflict-of-Interest Disclosures: Erin Fox discloses employment by the National Academies of Sciences, Engineering, and Medicine while this paper series was being drafted.

Competing Interests: Conflict-of-Interest Disclosures: Erin Fox discloses employment by the National Academies of Sciences, Engineering, and Medicine while this paper series was being drafted.

Background: Type 2 (T2) high asthma is recognised as a heterogenous entity consisting of several endotypes; however, the prevalence and distribution of the T2 biomarkers in the general asthma population, across asthma severity, and across compartments is largely unknown. The objective of the present study was to describe expression and overlaps of airway and systemic T2 biomarkers in a clinically representative asthma population., Methods: Patients with asthma from the real-life BREATHE cohort referred to a specialist centre were included and grouped according to T2 biomarkers: blood and sputum eosinophilia (≥0.3×10 9  cells·L -1 and 3% respectively), total IgE (≥150 U·mL -1 ), and fractional exhaled nitric oxide (≥25 ppb)., Results: Patients with mild-to-moderate asthma were younger (41 versus 49 years, p<0.001), had lower body mass index (25.9 versus 28.0 kg·m -2 , p=0.002) and less atopy (47% versus 58%, p=0.05), higher forced expiratory volume in 1 s (3.2 versus 2.8 L, p<0.001) and forced vital capacity (4.3 versus 3.9 L, p<0.001) compared with patients with severe asthma, who had higher blood (0.22×10 9 versus 0.17×10 9  cells·L -1 , p=0.01) and sputum (3.0% versus 1.5%, p=0.01) eosinophils. Co-expression of all T2 biomarkers was a particular characteristic of severe asthma (p<0.001). In patients with eosinophilia, sputum eosinophilia without blood eosinophilia was present in 45% of patients with mild-to-moderate asthma and 35% with severe asthma., Conclusion: Severe asthma is more commonly associated with activation of several T2 pathways, indicating that treatments targeting severe asthma may need to act more broadly on T2 inflammatory pathways. Implementation of airway inflammometry in clinical care is of paramount importance, as the best treatable trait is otherwise is overlooked in a large proportion of patients irrespective of disease severity., Competing Interests: Conflicts of interest: L. Frøssing, D.K. Klein, N. Obling, J.S. Erjefält and U. Bodtger report no conflicts of interest in relation to the current manuscript. M. Hvidtfeldt and C. Porsbjerg report unrestricted grants from Teva and AstraZeneca. G. Telg is employed by AstraZeneca Nordic., (Copyright ©The authors 2023.)

Introduction: Severe eosinophilic asthma is characterised by frequent exacerbations and a relative insensitivity to steroids. Experimentally, smoking may induce eosinophilic airway inflammation, but the impact in patients with severe asthma is not clear., Objective: To investigate the association between smoking exposure in patients with severe asthma, and eosinophilic inflammation and activation, as well as airway autoimmunity and steroid responsiveness., Methods: Patients with severe asthma according to European Respiratory Society/American Thoracic Society criteria were assessed with sputum samples, analysed by cell differential count, and for the presence of free eosinophil granules (FEGs), autoantibodies against eosinophil peroxidase (EPX) and macrophage receptor with collagenous structure (MARCO). A subgroup of patients with eosinophilic airway inflammation was re-assessed after a 2-week course of prednisolone., Results: 132 severe asthmatics were included in the study. 39 (29.5%) patients had ≥10 pack-years of smoking history: 36 (27.3%) were former smokers and three (2.3%) current smokers; and 93 (70.5%) had <10 pack-years exposure. Eosinophilic airway inflammation was more prevalent among patients with ≥10 pack-years (66.7%), compared to patients with <10 pack-years (38.7%, p=0.03), as was the level of FEGs (p=0.001) and both anti-EPX and anti-MARCO (p<0.05 and p<0.0001, respectively). Omitting current smokers did not affect these associations. Furthermore, prednisolone reduced, but did not normalise, sputum eosinophils in patients with a ≥10 pack-year smoking history., Conclusion: In patients with severe asthma, a former smoking history is associated with eosinophilic airway inflammation and activation and relative insensitivity to steroids, as well as airway autoimmunity., Competing Interests: Conflict of interest: D.K. Klein declares no competing interests. A. Silberbrandt declares no competing interests. L. Frøssing declares payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from GlaxoSmithKline, in the 36 months prior to manuscript submission. M. Hvidtfeldt declares no competing interests. A. von Bülow declares grants from Novartis Healthcare, Denmark; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, GlaxoSmithKline and Novartis; and participation on a data safety monitoring board or advisory board for Novartis, all in the 36 months prior to manuscript submission. P. Nair reports grants and personal fees from AstraZeneca, grants from Novartis, grants and personal fees from Teva, grants from Sanofi, grants and personal fees from Roche, personal fees from Novartis, personal fees from Merck, personal fees from Equillium, grants from Foresee, outside the submitted work. M. Mukherjee reports grants from Canadian Institutes of Health Research, grants from Methapharm Specialty Pharmaceuticals, personal fees from AstraZeneca, personal fees from GlaxoSmithKline, outside the submitted work. C. Porsbjerg declares grants, consulting fees and payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, GlaxoSmithKline, Novartis, Teva, Sanofi, Chiesi and ALK, all in the 36 months prior to manuscript submission., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Glanders is an equine zoonosis caused by Burkholderia mallei that is responsible for considerable economic loss. Complement fixation testing (CFT) using warm or cold incubation are recommended by the OIE, but many routinely used detection tests may present misleading results. To increase accuracy of glanders diagnosis and establish an appropriate protocol in collaboration with the National Equine Health Program, seven horses positive for glanders kept in isolation in Brazil were examined fortnightly by CFT, microbiological screening, and molecular testing. Warm and cold serologies with USDA and c.c.Pro antigens, respectively, were performed on 132 samples using the US Department of Agriculture protocol . The warm and cold serologies showed, respectively,12.9% and 17.3% seroreactive, 85.7% and 65.2% non-reactive, 0.8% and 3% inconclusive, and 0% and 2.3% anticomplementary. The agreement of CFT protocols was moderate. Of 213 clinical samples submitted to selective culture (167 nasal swabs, 5 ocular swabs, 3 lymph node punctures, and 38 tissue samples from four horses that died), 1.9% tested positive for B. mallei. Fourteen samples and one nasal swab (7%) tested positive with PCR. Cold CFT with the USDA and c.c.Pro antigens, in combination with PCR to increase sensitivity, may be useful for diagnosis of chronic glanders., Competing Interests: We are submitting the paper entitled “Systematic monitoring of glanders-infected horses by complement fixation test, bacterial isolation, and PCR “ for analysis by the editorial boarding of the Veterinary and Animal Science. We declare that there is no financial or personal relationship that could cause a conflict of interest regarding this article., (© 2020 The Authors. Published by Elsevier Ltd.)

Competing Interests: Conflict-of-Interest Disclosures: None to disclose.

Background: The BREATHE study is a cross-sectional study of real-life patients with asthma and/or COPD in Denmark and Sweden aiming to increase the knowledge across severities and combinations of obstructive airway disease. Design: Patients with suspicion of asthma and/or COPD and healthy controls were invited to participate in the study and had a standard evaluation performed consisting of questionnaires, physical examination, FeNO and lung function, mannitol provocation test, allergy test, and collection of sputum and blood samples. A subgroup of patients and healthy controls had a bronchoscopy performed with a collection of airway samples. Results: The study population consisted of 1403 patients with obstructive airway disease (859 with asthma, 271 with COPD, 126 with concurrent asthma and COPD, 147 with other), and 89 healthy controls (smokers and non-smokers). Of patients with asthma, 54% had moderate-to-severe disease and 46% had mild disease. In patients with COPD, 82% had groups A and B, whereas 18% had groups C and D classified disease. Patients with asthma more frequently had childhood asthma, atopic dermatitis, and allergic rhinitis, compared to patients with COPD, asthma + COPD and Other, whereas FeNO levels were higher in patients with asthma and asthma + COPD compared to COPD and Other (18 ppb and 16 ppb vs 12.5 ppb and 14 ppb, p  < 0.001). Patients with asthma, asthma + COPD and Other had higher sputum eosinophilia (1.5%, 1.5%, 1.2% vs 0.75%, respectively, p  < 0.001) but lower sputum neutrophilia (39.3, 43.5%, 40.8% vs 66.8%, p  < 0.001) compared to patients with COPD. Conclusions: The BREATHE study provides a unique database and biobank with clinical information and samples from 1403 real-life patients with asthma, COPD, and overlap representing different severities of the diseases. This research platform is highly relevant for disease phenotype- and biomarker studies aiming to describe a broad spectrum of obstructive airway diseases., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Objective: The present study examines the impact of Health Bucks, a farmers' market incentive programme, on awareness of and access to farmers' markets, and fruit and vegetable purchase and consumption in low-income New York City neighbourhoods., Design: The evaluation used two primary data collection methods: (i) an on-site point-of-purchase survey of farmers' market shoppers; and (ii) a random-digit-dial telephone survey of residents in neighbourhoods where the programme operates. Additionally, we conducted a quasi-experimental analysis examining differential time trends in consumption before and after programme introduction using secondary Community Health Survey (CHS) data., Setting: New York City farmers' markets and communities., Subjects: Farmers' market shoppers (n 2287) completing point-of-purchase surveys in a representative sample of New York City farmers' markets in 2010; residents (n 1025) completing random-digit-dial telephone survey interviews in 2010; and respondents (n 35 606) completing CHS interviews in 2002, 2004, 2008 and 2009., Results: Greater Health Bucks exposure was associated with: (i) greater awareness of farmers' markets; (ii) increased frequency and amount of farmers' market purchases; and (iii) greater likelihood of a self-reported year-over-year increase in fruit and vegetable consumption. However, our CHS analysis did not detect impacts on consumption., Conclusions: While our study provides promising evidence that use of farmers' market incentives is associated with increased awareness and use of farmers' markets, additional research is needed to better understand impacts on fruit and vegetable consumption.

Disability is an emerging field within public health; people with significant disabilities account for more than 12% of the US population. Disparity status for this group would allow federal and state governments to actively work to reduce inequities. We summarize the evidence and recommend that observed differences are sufficient to meet the criteria for health disparities: population-level differences in health outcomes that are related to a history of wide-ranging disadvantages, which are avoidable and not primarily caused by the underlying disability. We recommend future research and policy directions to address health inequities for individuals with disabilities; these include improved access to health care and human services, increased data to support decision-making, strengthened health and human services workforce capacity, explicit inclusion of disability in public health programs, and increased emergency preparedness.

Cells respond to DNA damage by activating cell cycle checkpoints to delay proliferation and facilitate DNA repair. Here, to uncover new checkpoint regulators, we perform RNA interference screening targeting genes involved in ubiquitylation processes. We show that the F-box protein cyclin F plays an important role in checkpoint control following ionizing radiation. Cyclin F-depleted cells initiate checkpoint signalling after ionizing radiation, but fail to maintain G2 phase arrest and progress into mitosis prematurely. Importantly, cyclin F suppresses the B-Myb-driven transcriptional programme that promotes accumulation of crucial mitosis-promoting proteins. Cyclin F interacts with B-Myb via the cyclin box domain. This interaction is important to suppress cyclin A-mediated phosphorylation of B-Myb, a key step in B-Myb activation. In summary, we uncover a regulatory mechanism linking the F-box protein cyclin F with suppression of the B-Myb/cyclin A pathway to ensure a DNA damage-induced checkpoint response in G2.

Introduction: One strategy for lowering the prevalence of obesity is to increase access to and affordability of fruits and vegetables through farmers' markets. However, little has been documented in the literature on the implementation of such efforts. To address this gap, the Division of Nutrition, Physical Activity, and Obesity (DNPAO) sponsored an evaluation of the New York City Health Bucks program, a farmers' market coupon incentive program intended to increase access to fresh fruits and vegetables in underserved neighborhoods while supporting local farmers., Methods: We conducted a process evaluation of Health Bucks program implementation. We interviewed 6 farmer/vendors, 3 market managers, and 4 program administrators, and collected data on site at 86 farmers' markets, including surveys of 81 managers and 141 farmer/vendors on their perspectives on promotion and redemption of the incentive coupons; knowledge and attitudes regarding the program; experiences with markets and products; and facilitators and barriers to program participation., Results: Results indicate that respondents view Health Bucks as a positive program model. Farmers' market incentive coupon programs like Health Bucks are one strategy to address the problem of obesity and were associated with higher fruit and vegetable access and purchases in low-income communities., Conclusions: This evaluation identified some areas for improving implementation of the Health Bucks program. Farmers' market incentive programs like Health Bucks may be one avenue to increase access to and affordability of fruits and vegetables among low-income persons. Further research is needed to assess the potential effects of these programs on access and health outcomes.

Although "population health" is one of the Institute for Healthcare Improvement's Triple Aim goals, its relationship to accountable care organizations (ACOs) remains ill-defined and lacks clarity as to how the clinical delivery system intersects with the public health system. Although defining population health as "panel" management seems to be the default definition, we called for a broader "community health" definition that could improve relationships between clinical delivery and public health systems and health outcomes for communities. We discussed this broader definition and offered recommendations for linking ACOs with the public health system toward improving health for patients and their communities.

To identify key connections between DNA-damage repair and checkpoint pathways, we performed RNA interference screens for regulators of the ionizing radiation-induced G2 checkpoint, and we identified the breast cancer gene BRCA2. The checkpoint was also abrogated following depletion of PALB2, an interaction partner of BRCA2. BRCA2 and PALB2 depletion led to premature checkpoint abrogation and earlier activation of the AURORA A-PLK1 checkpoint-recovery pathway. These results indicate that the breast cancer tumour suppressors and homologous recombination repair proteins BRCA2 and PALB2 are main regulators of G2 checkpoint maintenance following DNA-damage.

Exercising muscle releases interleukin-6 (IL-6), but the mechanisms controlling this process are poorly understood. This study was performed to test the hypothesis that the IL-6 release differs in arm and leg muscle during whole-body exercise, owing to differences in muscle metabolism. Sixteen subjects (10 men and six women, with body mass index 24 ± 1 kg m(-2) and peak oxygen uptake 3.4 ± 0.6 l min(-1)) performed a 90 min combined arm and leg cycle exercise at 60% of maximal oxygen uptake. The subjects arrived at the laboratory having fasted overnight, and catheters were placed in the femoral artery and vein and in the subclavian vein. During exercise, arterial and venous limb blood was sampled and arm and leg blood flow were measured by thermodilution. Lean limb mass was measured by dual-energy X-ray absorbtiometry scanning. Before and after exercise, biopsies were obtained from vastus lateralis and deltoideus. During exercise, IL-6 release was similar between men and women and higher (P < 0.05) from arms than legs (1.01 ± 0.42 and 0.33 ± 0.12 ng min(-1) (kg lean limb mass)(-1), respectively). Blood flow (425 ± 36 and 554 ± 35 ml min(-1) (kg lean limb mass)(-1)) and fatty acid uptake (26 ± 7 and 47 ± 7 μmol min(-1) (kg lean limb mass)(-1)) were lower, glucose uptake similar (51 ± 12 and 41 ± 8 mmol min(-1) (kg lean limb mass)(-1)) and lactate release higher (82 ± 32 and -2 ± 12 μmol min(-1) (kg lean limb mass)(-1)) in arms than legs, respectively, during exercise (P < 0.05). No correlations were present between IL-6 release and exogenous substrate uptakes. Muscle glycogen was similar in arms and legs before exercise (388 ± 22 and 428 ± 25 mmol (kg dry weight)(-1)), but after exercise it was only significantly lower in the leg (219 ± 29 mmol (kg dry weight)(-1)). The novel finding of a markedly higher IL-6 release from the exercising arm compared with the leg during whole-body exercise was not directly correlated to release or uptake of exogenous substrate, nor to muscle glycogen utilization.

The DNA damage induced G(2)/M checkpoint is an important guardian of the genome that prevents cell division when DNA lesions are present. The checkpoint prevents cells from entering mitosis by degrading CDC25A, a key CDK activator. CDC25A proteolysis is controlled by direct phosphorylation events that lead to its recognition by the ubiquitin ligase beta-TrCP. Recently we have identified NEK11, a member of NIMA-related kinase family, as the critical kinase triggering CDC25A degradation. NEK11 controls degradation of CDC25A by directly phosphorylating CDC25A on residues whose phosphorylation is required for beta-TrCP mediated CDC25A polyubiquitylation and degradation. The activity of NEK11 is in turn controlled by CHK1 that activates NEK11 via phosphorylation on serine 273. Since inhibition of NEK11 activity forces checkpoint-arrested cells into mitosis and cell death, NEK11 is, like CHK1, a strong candidate target for the development of novel anticancer drugs. Here we further support this notion by showing results suggesting that NEK11 expression increases during colon cancer development.

5'-AMP-activated protein kinase (AMPK) was recently suggested to regulate pyruvate dehydrogenase (PDH) activity and thus pyruvate entry into the mitochondrion. We aimed to provide evidence for a direct link between AMPK and PDH in resting and metabolically challenged (exercised) skeletal muscle. Compared with rest, treadmill running increased AMPKalpha1 activity in alpha(2)KO mice (90%, P < 0.01) and increased AMPKalpha2 activity in wild-type (WT) mice (110%, P < 0.05), leading to increased AMPKalpha Thr(172) (WT: 40%, alpha(2)KO: 100%, P < 0.01) and ACCbeta Ser(227) phosphorylation (WT: 70%, alpha(2)KO: 210%, P < 0.01). Compared with rest, exercise significantly induced PDH-E(1)alpha site 1 (WT: 20%, alpha(2)KO: 62%, P < 0.01) and site 2 (only alpha(2)KO: 83%, P < 0.01) dephosphorylation and PDH(a) [ approximately 200% in both genotypes (P < 0.01)]. Compared with WT, PDH dephosphorylation and activation was markedly enhanced in the alpha(2)KO mice both at rest and during exercise. The increased PDH(a) activity during exercise was associated with elevated glycolytic flux, and muscles from the alpha(2)KO mice displayed marked lactate accumulation and deranged energy homeostasis. Whereas mitochondrial DNA content was normal, the expression of several mitochondrial proteins was significantly decreased in muscle of alpha(2)KO mice. In isolated resting EDL muscles, activation of AMPK signaling by AICAR did not change PDH-E(1)alpha phosphorylation in either genotype. PDH is activated in mouse skeletal muscle in response to exercise and is independent of AMPKalpha2 expression. During exercise, alpha(2)KO muscles display deranged energy homeostasis despite enhanced glycolytic flux and PDH(a) activity. This may be linked to decreased mitochondrial oxidative capacity.

AMP-activated protein kinase (AMPK) is a heterotrimeric protein that regulates glucose transport mediated by cellular stress or pharmacological agonists such as 5-aminoimidazole-4-carboxamide 1 beta-d-ribonucleoside (AICAR). AS160, a Rab GTPase-activating protein, provides a mechanism linking AMPK signaling to glucose uptake. We show that AICAR increases AMPK, acetyl-CoA carboxylase, and AS160 phosphorylation by insulin-independent mechanisms in isolated skeletal muscle. Recombinant AMPK heterotrimeric complexes (alpha1beta1gamma1 and alpha2beta2gamma1) phosphorylate AS160 in a cell-free assay. In mice deficient in AMPK signaling (alpha2 AMPK knockout [KO], alpha2 AMPK kinase dead [KD], and gamma3 AMPK KO), AICAR effects on AS160 phosphorylation were severely blunted, highlighting that complexes containing alpha2 and gamma3 are necessary for AICAR-stimulated AS160 phosphorylation in intact skeletal muscle. Contraction-mediated AS160 phosphorylation was also impaired in alpha2 AMPK KO and KD but not gamma3 AMPK KO mice. Our results implicate AS160 as a downstream target of AMPK.

Public health researchers and practitioners have begun to recognize the dynamic nature of disability, promote the health of people with disabilities, and develop strategies to prevent secondary conditions among them. To understand the epidemiology of secondary conditions, the authors developed the Massachusetts Survey of Secondary Conditions, a longitudinal study of adults with major disabilities (n = 656) based on a conceptual framework linking disability, mediating factors, and health outcomes. This paper reports baseline data on the number of secondary conditions experienced by survey respondents. Respondents experienced a mean of 5.3 of 17 secondary conditions. More numerous secondary conditions were associated with fair or poor general health and number of days unable to do routine activities. Factors amenable to public health interventions included difficulty with weight and exercise maintenance, tobacco and marijuana use, and experiencing assault. Disability should be a focus in all public health research, policy, and programs.