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Objectives: This review aims to explore potential associations between immunological biomarkers and phonotraumatic vocal fold lesions., Study Design: Scoping review., Methods: Ovid MEDLINE, CINAHL, PubMed, Proquest Theses and Dissertations, Scopus, and Web of Science were searched using the terms "vocal fold" and "inflammatory marker" initially, and later "development" and "phonotraumatic lesion." Papers were included for review if they were published in the last 20 years in English language, used human cell lines or biological samples, and outcomes were measured objectively using immunological biomarkers., Results: In total, 4107 papers were identified for screening. The automation tools EndNote and Covidence removed 1257 duplicates. A further 2687 papers were excluded by reviewers at the title and abstract screening stage. The remaining 62 papers underwent full-text screening and 28 publications were ultimately included in the review., Conclusions: Research concerning the possible association between immunological biomarkers and phonotraumatic lesions is still in its early stages, largely due to difficulty obtaining biological vocal fold samples in a safe and noninvasive manner, and challenges in identifying laboratory techniques that are sensitive enough to detect concentrations of biomarkers in small volumes of vocal fold samples. Signaling molecules are likely the most promising biomarkers to investigate the role of voice use patterns in the development of phonotraumatic lesions due to relatively rapid shifts in response to host conditions. Future research would benefit from control of potential systemic contributions to laryngeal manifestations of inflammation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: High-dose corticosteroids have been used to attenuate the inflammatory response to cardiac surgery and cardiopulmonary bypass, but patient outcome benefits remain unclear. The primary aim was to determine whether using dexamethasone was superior to not using dexamethasone to increase the number of home days in the first 30 days after cardiac surgery. The secondary aim was to evaluate efficiency, value, and impact of the novel trial design., Methods: This pragmatic, international trial incorporating a prerandomized consent design favoring local practice enrolled patients undergoing cardiac surgery across seven hospitals in Australia and The Netherlands. Patients were randomly assigned to dexamethasone 1 mg/kg or not (control). The primary outcome was the number of days alive and at home up to 30 days after surgery ("home days"). Secondary outcomes included prolonged mechanical ventilation (more than 48 h), sepsis, renal failure, myocardial infarction, stroke, and death., Results: Of 2,562 patients assessed for eligibility, 1,951 were randomized (median age, 63 yr; 80% male). The median number of home days was 23.0 (interquartile range, 20.1 to 24.1) in the no dexamethasone group and 23.1 (interquartile range, 20.1 to 24.6) in the dexamethasone group (median difference, 0.1; 95% CI, -0.3 to 0.5; P = 0.66). The rates of prolonged mechanical ventilation (risk ratio, 0.72; 95% CI, 0.48 to 1.08), sepsis (risk ratio, 1.02; 95% CI, 0.57 to 1.82), renal failure (risk ratio, 0.94; 95% CI, 0.80 to 1.12), myocardial infarction (risk ratio, 1.20; 95% CI, 0.30 to 4.82), stroke (risk ratio, 1.06; 95% CI, 0.54 to 2.08), and death (risk ratio, 0.72; 95% CI, 0.22 to 2.35) were comparable between groups (all P > 0.10). Dexamethasone reduced intensive care unit stay (median, 29 h; interquartile range, 22 to 50 h vs. median, 43 h; interquartile range, 24 to 72 h; P = 0.004). The authors' novel trial design was highly efficient (89.3% enrollment)., Conclusions: Among patients undergoing cardiac surgery, high-dose dexamethasone decreased intensive care unit stay but did not increase the number of home days after surgery., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

The microfossil record contains abundant, diverse, and well-preserved fossils spanning multiple trophic levels from primary producers to apex predators. In addition, microfossils often constitute and are preserved in high abundances alongside continuous high-resolution geochemical proxy records. These characteristics mean that microfossils can provide valuable context for understanding the modern climate and biodiversity crises by allowing for the interrogation of spatiotemporal scales well beyond what is available in neo-ecological research. Here, we formalize a research framework of "micropaleoecology," which builds on a holistic understanding of global change from the environment to ecosystem level. Location: Global. Time period: Neoproterozoic-Phanerozoic. Taxa studied: Fossilizing organisms/molecules. Our framework seeks to integrate geochemical proxy records with microfossil records and metrics, and draws on mechanistic models and systems-level statistical analyses to integrate disparate records. Using multiple proxies and mechanistic mathematical frameworks extends analysis beyond traditional correlation-based studies of paleoecological associations and builds a greater understanding of past ecosystem dynamics. The goal of micropaleoecology is to investigate how environmental changes impact the component and emergent properties of ecosystems through the integration of multi-trophic level body fossil records (primarily using microfossils, and incorporating additional macrofossil data where possible) with contemporaneous environmental (biogeochemical, geochemical, and sedimentological) records. Micropaleoecology, with its focus on integrating ecological metrics within the context of paleontological records, facilitates a deeper understanding of the response of ecosystems across time and space to better prepare for a future Earth under threat from anthropogenic climate change., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Degradation of the endothelial glycocalyx in type 2 diabetes (T2D) is thought to contribute to impaired shear stress mechanotransduction, leading to endothelial dysfunction and the development of cardiovascular disease. Herein, we tested the hypothesis that restoration of the endothelial glycocalyx with dietary supplementation of glycocalyx precursors (DSGP, containing glucosamine sulfate, fucoidan, superoxide dismutase, and high molecular weight hyaluronan) improves endothelial function and other indices of vascular function in T2D. First, in db/db mice, we showed that treatment with DSGP (100 mg/kg/day) for four weeks restored endothelial glycocalyx length, as assessed via atomic force microscopy in aortic explants. Restoration of the glycocalyx with DSGP was accompanied by improved flow-mediated dilation (FMD) and reduced arterial stiffness in isolated mesenteric arteries. Further corroborating these findings, treatment of cultured endothelial cells with that same mixture of glycocalyx precursors promoted glycocalyx growth. Next, as an initial step to investigate the translatability of these findings, we conducted a pilot (n=22) double-blinded randomized placebo-controlled clinical trial to assess the effects of DSGP (3,712.5 mg/day) for eight weeks on endothelial glycocalyx integrity and indices of vascular function, including FMD, in Veterans with T2D. Contrary to the hypothesis, DSGP neither enhanced endothelial glycocalyx integrity nor improved vascular function indices relative to placebo. Together, these findings conceptually support the notion that restoration of the endothelial glycocalyx can lead to improvements in vascular function in a mouse model of T2D; however, DSGP as a therapeutic strategy to enhance vascular function in individuals with T2D does not appear to be efficacious.

Background: There is evidence that engaging in research is directly associated with better performance. If this relationship is to be strengthened, it is necessary to understand the mechanisms that might underlie that relationship., Aim: To explore the perspectives of staff and wider stakeholders about mechanisms by which research activity may impact on the performance of general practices., Design & Setting: Qualitative study using semi-structured interviews with general practice professionals and wider stakeholders in England., Method: Individual interviews with 41 purposively sampled staff in 'research-ready' or 'research-active' general practices, and 21 other stakeholders. Interviews were independently coded by three researchers using a framework approach., Results: Participants described potential 'direct' and 'indirect' impacts on their work. 'Direct' impacts included improved knowledge and skills that could change practice work (for example, additional records searches for particular conditions); bringing in additional resources (for example, access to investigations or staff); and improving relationships with patients. 'Indirect' impacts included job satisfaction (for example, perception of practice as a centre of excellence and innovation, and the variety afforded by research activity reducing burnout); and staff recruitment (increasing the attractiveness of the practice as a place to work). Responders identified few negative impacts., Conclusion: Staff and stakeholders identified a range of potential impacts of research activity on practice performance, with impacts on their working lives most salient. Negative impacts were not generally raised. Nevertheless, responders generally discussed potential impacts rather than providing specific examples of those impacts. This may reflect the type of research activity conducted in general practice, often led by external collaborators., (Copyright © 2024, The Authors.)

Instruments attached to animals ('biologgers') have facilitated extensive discoveries about the patterns, causes, and consequences of animal behavior. Here, we present examples of how biologging can deepen our fundamental understanding of ecosystems and our applied understanding of global change impacts by enabling tests of ecological theory. Applying the iterative process of science to biologging has enabled a diverse set of insights, including social and experiential learning in long-distance migrants, state-dependent risk aversion in foraging predators, and resource abundance driving movement across taxa. Now, biologging is poised to tackle questions and refine ecological theories at increasing levels of complexity by integrating measurements from numerous individuals, merging datasets from multiple species and their environments, and spanning disciplines, including physiology, behavior and demography., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Epigenome-wide association studies have identified multiple DNA methylation sites (CpGs) associated with alcohol consumption, an important lifestyle risk factor for cardiovascular diseases. This study aimed to test the hypothesis that an alcohol consumption epigenetic risk score (ERS) is associated with blood pressure (BP) traits., Results: We implemented an ERS based on a previously reported epigenetic signature of 144 alcohol-associated CpGs in meta-analysis of participants of European ancestry. We found a one-unit increment of ERS was associated with eleven drinks of alcohol consumed per day, on average, across several cohorts (p < 0.0001). We examined the association of the ERS with systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension (HTN) in 3,898 Framingham Heart Study (FHS) participants. Cross-sectional analyses in FHS revealed that a one-unit increment of the ERS was associated with 1.93 mm Hg higher SBP (p = 4.64E-07), 0.68 mm Hg higher DBP (p = 0.006), and an odds ratio of 1.78 for HTN (p < 2E-16). Meta-analysis of the cross-sectional association of the ERS with BP traits in eight independent external cohorts (n = 11,544) showed similar relationships with BP levels, i.e., a one-unit increase in ERS was associated with 0.74 mm Hg (p = 0.002) higher SBP and 0.50 mm Hg (p = 0.0006) higher DBP, but not with HTN. Longitudinal analyses in FHS (n = 3260) and five independent external cohorts (n = 4021) showed that the baseline ERS was not associated with a change in BP over time or with incident HTN., Conclusions: Our findings demonstrate that the ERS has potential clinical utility in assessing lifestyle factors related to cardiovascular risk, especially when self-reported behavioral data (e.g., alcohol consumption) are unreliable or unavailable., (© 2024. The Author(s).)

Human disturbance is contributing to widespread, global changes in the distributions and densities of wild animals. These anthropogenic impacts on wildlife arise from multiple bottom-up and top-down pathways, including habitat loss, resource provisioning, climate change, pollution, infrastructure development, hunting and our direct presence. Animal behaviour is an important mechanism linking these disturbances to population outcomes, although these behavioural pathways are often complex and can remain obscured when different aspects of behaviour are studied in isolation from one another. The spatial-social interface provides a lens for understanding how an animal's spatial and social environments interact to determine its spatial and social phenotype (i.e. measurable characteristics of an individual), and how these phenotypes interact and feed back to reshape environments. Here, we review studies of animal behaviour at the spatial-social interface to understand and predict how human disturbance affects animal movement, distribution and intraspecific interactions, with consequences for the conservation of populations and ecosystems. By understanding the spatial-social mechanisms linking human disturbance to conservation outcomes, we can better design management interventions to mitigate undesired consequences of disturbance.This article is part of the theme issue 'The spatial-social interface: a theoretical and empirical integration'.

Background: Studies estimating risks following cardiac surgery for patients receiving kidney replacement therapy have been limited by the size and generalizability of those cohorts. This study used data linked between registries to estimate short-term postoperative outcomes for large patient cohorts receiving kidney replacement therapy at the time of surgery., Methods: This population-based observational cohort study included adult patients who had undergone cardiac surgery in Australia between 2010 and 2019. Patient data were linked with a kidney replacement therapy registry to accurately identify cohorts and extract relevant data. Multivariable logistic regression estimated risk of operative (30-day) mortality and other postoperative outcomes for long-term dialysis and functioning kidney transplant cohorts compared with each other and the general cardiac surgical population., Results: Of 114,496 surgeries, 1,241 were for patients receiving long-term dialysis and 298 for those with a kidney transplant. The mortality rate was highest for valve-with-coronary artery bypass grafting for dialysis (18.78 per 100 surgeries (95% CI 13.37,25.25) and transplant patients (14.00 [5.82,26.74]). Dialysis patients had higher adjusted odds of mortality (odds ratio [OR] 4.17 [95% CI 3.31,5.25]) and all other measured outcomes than the general population. Kidney transplant recipients had similarly elevated odds of mortality (OR 3.52 [95% CI 2.16,5.72])., Conclusions: Despite the younger age of dialysis and transplant cohorts at surgery, operative mortality rates were higher, and for valve-with-coronary artery bypass grafting were 3.7- to 5-fold those of the general population. Dialysis patients were a high risk for cardiac surgery, and the prognosis for kidney transplant recipients was similarly poor., (Copyright © 2024. Published by Elsevier Inc.)

Objective/hypothesis: To compare the systemic changes following two office-based procedures-subepithelial vocal fold steroid injections (VFSI) and vocal fold augmentation (VFA), and to characterize the magnitude and chronicity of the effects observed., Study Design: Prospective, controlled before-after comparative study., Methods: Patients prospectively underwent VFSI with 0.8-2 mg of dexamethasone or VFA. Serum cortisol, white cell count (WCC), and C-reactive protein (CRP) were measured at day 0 (pre-procedure), 1 and 7. Salivary cortisol was measured at baseline and daily for 7 days post-procedure., Results: Fourteen patients underwent VFSI and 36 VFA. At baseline serum cortisol measured 304.6 ± 116.6 nmol/L and fell significantly to 48.1 ± 41.8 nmol/L 1 day following dexamethasone injection (p = 0.001) and recovered by day 7 to 303.7 ± 78.7 nmol/L. Salivary cortisol demonstrated a similar pattern with significant recovery demonstrated by day 3 (p = 0.001). White cell counts were affected by the systemic absorption of exogenous steroid and normalized by day 7. Patients who underwent VFA demonstrated no significant change in their serum or salivary cortisol and no significant change in their WCC. No significant changes in CRP or patient's physiological parameters were observed in either procedure., Conclusion: Our findings demonstrate systemic absorption of dexamethasone following VFSI, with acute hypothalamic-pituitary-adrenal (HPA) axis suppression which normalizes day 3 post-procedurally., Level of Evidence: 3 Laryngoscope, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Multidisciplinary endocarditis team (MDET) management is supported by current evidence and recommended in international society guidelines. The extent to which this recommendation has been implemented in Australian centres and the attitudes, barriers and facilitators of this model are unclear., Aim: To describe current infective endocarditis (IE) models of care in Australian specialist referral centres and evaluate facilitators, barriers and attitudes towards MDET implementation., Methods: Aims were addressed using two online surveys. Survey 1 audited IE models of care and was distributed to infectious disease physicians at specialist referral centres. Survey 2 assessed barriers, facilitators and attitudes towards MDETs and was distributed via societal email listings., Results: From 56 identified cardiac surgery centres, survey 1 received 47 responses (84%). A total of 28% (13/47) of participating institutions had an existing MDET. A total of 85% (11/13) of MDETs were in public hospitals and 85% (11/13) were in high IE volume centres. Survey 2 had 109 respondents from seven specialties. Attitudes towards MDET implementation were generally favourable. Identified barriers to MDET implementation included a lack of funding, resources, expertise, time and collaboration. Facilitators included strong leadership, engagement from key stakeholders and tangible benefits., Conclusions: Even though it is recommended in international guidelines, the MDET model is used by less than one-third of Australian specialist referral centres. Stakeholders in IE care have generally favourable attitudes towards MDET implementation but cite a lack of resources, funding, collaboration and time as barriers to this. Dedication of financial and administrative support and leadership from key stakeholders are required to increase MDET utilisation., (© 2024 The Author(s). Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Whole genome sequences (WGS) enable discovery of rare variants which may contribute to missing heritability of coronary artery disease (CAD). To measure their contribution, we apply the GREML-LDMS-I approach to WGS of 4949 cases and 17,494 controls of European ancestry from the NHLBI TOPMed program. We estimate CAD heritability at 34.3% assuming a prevalence of 8.2%. Ultra-rare (minor allele frequency ≤ 0.1%) variants with low linkage disequilibrium (LD) score contribute ~50% of the heritability. We also investigate CAD heritability enrichment using a diverse set of functional annotations: i) constraint; ii) predicted protein-altering impact; iii) cis-regulatory elements from a cell-specific chromatin atlas of the human coronary; and iv) annotation principal components representing a wide range of functional processes. We observe marked enrichment of CAD heritability for most functional annotations. These results reveal the predominant role of ultra-rare variants in low LD on the heritability of CAD. Moreover, they highlight several functional processes including cell type-specific regulatory mechanisms as key drivers of CAD genetic risk., (© 2024. The Author(s).)

Background: Cough severity represents an important endpoint to assess the impact of therapies for patients with refractory chronic cough (RCC)., Objective: To develop a new patient-reported outcome measure addressing cough severity in patients with RCC., Methods: Phase 1 (item generation): A systematic survey, focus groups, and expert consultation generated 51 items. Phase 2 (item reduction): From a list of 51 items, 100 patients identified those they had experienced in the previous year and rated their importance on a 5-point scale. The MCSQ included items reported to occur most frequently and that had the highest importance scores. Patient feedback on the MCSQ led to elimination of redundant items. Another 100 patients completed the MCSQ, from which we performed an exploratory factor analysis and a Rasch analysis to further refine items on the MCSQ., Results: Phase 2 led to selection of 15 items from the initial 51. Patient feedback on the 15 items led to elimination of 5 redundant items. An exploratory factor analysis of the 10-item MCSQ led to selection of two domains, elimination of one item that demonstrated cross-loading, and another that had high inter-item correlations. A Rasch analysis of the 8-item MCSQ confirmed that the response options functioned in a logically progressive manner and that no items exhibited differential item functioning. The final 8-item MCSQ has a one-week recall period and includes two domains (intensity and frequency). The 8-item MCSQ had high internal consistency (Cronbach's alpha, 0.89), proved able to distinguish different levels of cough severity (Pearson separation index, 0.89), and demonstrated high cross-sectional convergent validity (Pearson's correlation, 0.76 [95% CI 0.66 to 0.83]) with the 100-mm cough severity visual analogue scale., Conclusion: Initial evidence supports the validity of the MCSQ, an 8-item instrument measuring cough severity in patients with RCC. Future studies should evaluate its properties in measuring change over time., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Multifactorial cancer risk prediction tools, such as CanRisk, are increasingly being incorporated into routine healthcare. Understanding risk information and communicating risk is challenging and healthcare professionals rely substantially on the outputs of risk prediction tools to communicate results. This work aimed to produce a new CanRisk report so users can directly access key information and communicate risk estimates effectively., Methods: Over a 13-month period, we led an 8-step co-design process with patients, the public, and healthcare professionals. Steps comprised 1) think aloud testing of the original CanRisk report; 2) structured feedback on the original report; 3) literature review; 4) development of a new report prototype; 5) first round of structured feedback; 6) updating the new report prototype; 7) second round of structured feedback; and 8) finalising and publishing the new CanRisk report., Results: We received 56 sets of feedback from 34 stakeholders. Overall, the original CanRisk report was not suitable for patients and the public. Building on the feedback, the new report has an overview of the information presented: section one summarises key information for individuals; sections two and three present information for healthcare professionals in different settings. New features also include explanatory text, definitions, graphs, keys and tables to support the interpretation of the information., Discussion: This co-design experience shows the value of collaboration for the successful communication of complex health information. As a result, the new CanRisk report has the potential to better support shared decision-making processes about cancer risk management across clinical settings., (© 2024. The Author(s).)