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Pre-participation screening and management of congenital cardiac valvulopathy in competitive athletes can be challenging, particularly within the context of ultra-endurance disciplines. A 55-year-old female athlete without a reported history of cardiac disease exhibited clinical signs of cardiogenic pulmonary edema during a 156 km ultra-trail race. The echocardiographic assessment revealed the presence of a parachute mitral valve, with no evidence of mitral stenosis or regurgitation at rest, but it demonstrated severe dynamic mitral stenosis during exercise. In competitive athletes, the detection of rare valvulopathy should prompt a comprehensive cardiac evaluation aimed at assessing the potential for dynamic valvular dysfunction. [ABSTRACT FROM AUTHOR]

The left ventricular end-diastolic pressure (LVEDP), a marker of diastolic function, is strongly influenced by cardiac preload. In vitro experiments have demonstrated that LVEDP is also affected by intracardiac hydrostatic pressure gradients, which depend on heart's orientation. Though lacking clinical validation, the relationship between intracardiac hydrostatic pressure gradient and cardiac filling could significantly impact the symptomatology of heart failure patients and the interpretation of cardiac function in clinical imaging. The aim was to isolate the intracardiac pressure gradient's effect independently of preload, exploring the orientation dependency of cardiac function in healthy and diabetic individuals. This prospective study aimed to recruit 32 subjects (16 healthy and 16 with diabetes), sequentially exposed to acute alterations of cardiac preload in various heart orientations: supine position via Lower Body Negative Pressure (LBNP) and upright position via Head-Up Tilt (HUT) test. Using a standardized protocol, all subjects underwent gradual preload variations during HUT (22°, 42°, 58°, and 80°) and LBNP (−10, −20, −35, −50 torr). Arterial blood pressure was continuously monitored non-invasively, while thoracic fluid shifts were assessed using bioelectrical impedance. Cardiac dimensions and left ventricular systolic and diastolic functions were evaluated at each stage via transthoracic echocardiography. Hemodynamic and fluid shift responses were collected from 20 subjects to date (7 healthy and 13 with diabetes). The current sample size per group precludes intergroup comparisons. Both LBNP and HUT induced comparable fluid shifts in the thoracic region, resulting in similar preload modifications (Fig. 1A). Blood pressure regulation was appropriate in both conditions, maintaining mean arterial blood pressure stable, except during HUT at 80° (Fig. 1B). A significant difference in stroke volume was observed between HUT at 80° and LBNP at −50 torr, with the latter associated with an uncompensated drop in stroke volume (Fig. 1C). Cardiac adaptation to upright posture effectively compensates for preload reduction, unlike in the supine position. Despite similar preload variations, intracardiac hydrostatic pressure in an upright posture sustains cardiac stroke volume, potentially due to gravitational effects. Confirmation through echocardiographic analysis, especially in diabetic subjects prone to early myocardial impairments, could significantly impact cardiac function interpretation in clinical practice and have important implications in aerospace medicine. [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathies encompass a heterogeneous group. Atrial strain is becoming increasingly valuable in detecting and quantifying early functional alterations in atrial function in these cardiomyopathies. This atrial deformation can provide previously unknown insights into atrial function and its modifications induced by various etiologies. However, their effects on atrial function and stiffness (Left Atrial Stiffness) have been poorly explored. We aimed to explore specific alterations in atrial function in hypertrophic cardiomyopathies by evaluating atrial stiffness (LAS/(E/Ea) among different types of left ventricular hypertrophy (LVH). The ultimate goal is to predict the underlying etiology of LVH on cardiac ultrasound through this atrial stiffness. Our retrospective observational cohort study, conducted at the University Hospital Center of Caen-Normandy from 2020 to 2023 (n = 142 patients), focused on adult patients with confirmed etiology of a LVH (LVH ≥ 12 mm on ultrasound), including genetic mutation for Fabry disease, sarcomeric hypertrophic cardiomyopathy, cardiac amyloidosis (Any type of amyloidosis, treated or not) or hypertensive cardiomyopathy. Demographic characteristics and biological characteristics were collected. Transthoracic echocardiographic assessments were conducted using ASE/EACVI guidelines (Philips EPIQ®). Atrial strain was retrospectively measured using PHILIPS® QLAB software. 52% of cardiac amyloidosis were in atrial fibrillation, 13% for sarcomeric hypertrophic cardiomyopathy. Statistical analysis (Kruskal-Wallis and Dunn's test) was performed (software R v4) to assess significant differences between groups. ROC curves were generated to differentiate etiologies of LVH. Significant differences in Left Atrial Stiffness were observed among the groups (Figure 1). Sarcomeric hypertrophic cardiomyopathy showing an average stiffness of 2.84 ± 2.0, amyloidosis 0.99 ± 0.85, hypertensive cardiomyopathy 3.5 ± 1.4, Fabry disease 2.37 ± 1.68 (P ≤ 0.001). ROC curve analysis for amyloidosis indicated excellent sensitivity and specificity for LAS/(E/Ea) ≤ 1.108 (sensitivity ≈ 89%, specificity ≈ 87%, AUC = 0.922). The presence of left ventricular hypertrophy with atrial stiffness value (LAS/(E/Ea) less than 1.108) appears to be one of the most sensitive and specific indicators of cardiac amyloidosis. [ABSTRACT FROM AUTHOR]

Cancer treatments, including radiation therapy, can lead to severe financial hardship during and after the treatment process. Oncology financial advocacy (FA) programs deliver services that can prevent or mitigate financial stress. While less financial assistance resources are available in the radiation oncology setting, interventions such as financial distress screening, patient education, scheduling flexibility, subsidizing transportation, and financial toxicity tumor boards can minimize financial distress for patients undergoing radiation therapy. In 2023, the Association of Cancer Care Centers (ACCC) conducted discussions with members to identify barriers for delivering FA services to radiation therapy patients. Building on those findings, ACCC's Financial Advocacy Network conducted a member Census in 2023 to determine the educational requirements for enhancing the expertise and abilities of financial advocates and navigators. ACCC convened an expert multidisciplinary advisory committee to guide this research. A Census was authored and distributed to ACCC member programs between May 1 – June 20, 2023. Clinical and non-clinical health care professionals involved in delivering FA services to people with cancer were invited to participate. The Census was administered via a survey platform and included 19 structured response and 5 open-ended response questions. Exploratory analysis was performed to identify themes relevant to patients receiving radiation therapy. 95 respondents representing 70 unique organizations and 31 states participated in the Census. Most respondents were financial advocates (36%), followed by administrators (34%), nurse/nurse navigators (14%), and patient navigators (11%). When asked to identify topics for preferred education and resources, 55% of respondents identified the need for additional FA interventions for radiation oncology – the fourth most common response out of a list of 15 topics. Other top education needs included deeper dives into FA functions (71%), financial health literacy (62%), and financial distress screening (55%). Additionally, the top challenge faced when delivering FA services were a lack of financial resources available to help patients (74%). In the face of limited financial resources to facilitate patient care, the development of strategies and interventions to alleviate financial distress for patients receiving radiation treatment has been identified as a primary FA educational need by cancer centers throughout the United States. These insights will guide ACCC in setting education priorities for radiation oncology staff, including the distribution of ACCC's Financial Advocacy Services Guidelines. The guidelines provide a framework for enhancing the ability to deliver FA services equitably to all cancer patients including those receiving radiation therapy. [ABSTRACT FROM AUTHOR]

Babesia species are intraerythrocytic piroplasms that can result in disease characterized by hemolytic anemia and thrombocytopenia. Of the 5 species that are known to infect canids in the United States, Babesia conradae is most frequently diagnosed in California, and Babesia vogeli is prevalent in the US. Despite the recent re-emergence of B. conradae , the mechanism of transmission is not known. Coyotes (Canis latrans) have been a proposed reservoir of disease, and previous work has shown that dogs with known aggressive interactions with coyotes are at greater risk for infection. This study aimed to determine the prevalence of B. conradae in wild coyote populations in California to assess the viability of coyotes as a potential source of infection for domestic dogs. Four hundred and sixty-one splenic samples were obtained during post-mortem examination of coyote carcasses from Southern California, Fresno, and Hopland. Demographic data including age, sex, cause of death, and urbanity were collected for each coyote. DNA was extracted from samples and amplified using real-time PCR with primers specific for the B. conradae ITS-2 gene. The 18S gene was amplified and sequenced using conventional PCR primers specific to the Babesia genus from any coyotes positive for B. conradae. In total, 22 coyotes tested positive for B. conradae in Fresno (n = 15), Orange (n = 4), San Bernardino (n = 1), and Los Angeles counties (n = 1) with an overall prevalence of 4.8%. Coyotes from Fresno (P<.01) and rural coyotes (P<.01) were significantly more likely to be infected with B. conradae. Ten of 14 samples sequenced were 99–100% homologous to B. conradae, and 4 samples were 100% homologous with B. vogeli DNA indicating co-infection with both pathogens. This study demonstrates that coyotes can become infected and harbor B. conradae and B. vogeli and should be investigated as a possible source of infection in domestic dogs. [Display omitted] • The first detection of Babesia conradae and Babesia vogeli via PCR in free-ranging Californian coyotes. • The PCR prevalence of B. conradae in all cities sampled was 4.8%; the city of Fresno had a prevalence of 31.9%. • Coyotes from Fresno (P <.01) and rural coyotes (P <.01) were significantly more likely to be infected with B. conradae. [ABSTRACT FROM AUTHOR]

Urolithin A (UA) is a gut metabolite derived from ellagic acid. This systematic review assesses the potential geroprotective effect of UA in humans. In five studies including 250 healthy individuals, UA (10–1000 mg/day) for a duration ranging from 28 days to 4 months, showed a dose-dependent anti-inflammatory effect and upregulated some mitochondrial genes, markers of autophagy, and fatty acid oxidation. It did not affect mitochondrial maximal adenosine triphosphate production, biogenesis, dynamics, or gut microbiota composition. UA increased muscle strength and endurance, however, had no effect on anthropometrics, cardiovascular outcomes, and physical function. Unrelated adverse events were mild or moderate. Further research across more physiological systems and longer intervention periods is required. • Urolithin A (UA), derived from ellagic acid-rich foods, extends healthspan and lifespan in animal models. • In humans, UA shows a potential effect on decreasing inflammation and enhancing muscle strength and endurance. • The impact of UA on human healthspan and lifespan requires further exploration. [ABSTRACT FROM AUTHOR]

Sodium glucose co-transporter-2 inhibitors (SGLT-2i) are increasingly being used among hospitalized patients. Our objective was to assess the risk of diabetic ketoacidosis (DKA) among hospitalized patients receiving an SGLT-2i. We conducted a multicentre cohort study of patients hospitalized at 19 hospitals. We included patients over 18 years of age who received an SGLT-2i or a dipeptidyl peptidase-4 inhibitor (DPP-4i) in hospital. The primary outcome was the risk of DKA during their hospitalization. 61,517 patients received a DPP-4i and 11,061 received an SGLT-2i. The risk of inpatient DKA was 0.07 % (N = 41 events) among adults who received a DPP-4i and 0.18 % (N = 20 events) among adults who received an SGLT-2i; adjusted odds ratio of 3.30 (95 % CI: 1.85–5.72). In hospitalized patients, the absolute risk of DKA was 0.2 %, which corresponded to a three-fold higher relative risk. • We conducted a multicentre cohort study of hospitalized adults to examine the risk of diabetic ketoacidosis (DKA) among patients who received an SGLT2 inhibitor in hospital (SGLT-2i). • The absolute risk of DKA with SGLT-2i was 0.2%, results consistent with a recent meta-analysis of SGLT-2i use in the outpatient setting. [ABSTRACT FROM AUTHOR]

Alcohol dependence is a chronic relapsing mental disorder with heterogeneous and complex underlying biology. It is frequently associated with nicotine dependence, severity of alcohol dependence symptoms, and diverse alcohol-related phenotypes, including the presence of delirium tremens and withdrawal symptoms, early or late onset of alcohol abuse, aggression, suicidal behavior, and anxiety. While searching for peripheral biomarkers of altered serotonergic (5-HT) function in alcohol dependence and alcohol-related behaviors, we determined a peripheral biomarker, i.e., platelet 5-HT concentration in a large group of Caucasian subjects with alcohol dependence subdivided according to the presence of specific alcohol-related phenotypes and smoking status. Individuals with alcohol dependence (n = 661) of both sexes were evaluated using Structural Clinical Interview based on DSM-IV criteria, while platelet 5-HT concentration was determined using the spectrophotofluorimetric method. Smoking is significantly associated, while sex and age are not, with platelet 5-HT concentration. Severe alcohol dependence and lack of withdrawal symptoms were associated with significantly decreased platelet 5-HT concentration in alcohol-dependent non-smokers. In smokers, significantly lower platelet 5-HT concentration was found in patients with the late onset of alcohol abuse. These results suggested that platelet 5-HT concentration might be used as a peripheral marker of different alcohol-related phenotypes, after controlling for the effects of smoking and sex. [ABSTRACT FROM AUTHOR]

Oxidized phospholipids (OxPLs) containing enzymatically or non-enzymatically oxidized fatty acids (oxylipins) are increasingly recognized as lipid mediators involved in pathogenesis of diseases. Further understanding of structure-activity relationship and molecular mechanisms activated by OxPLs is hampered by the complexity of synthesis of individual molecular species. Although dozens of individual free oxylipins are commercially available, their attachment to the phospholipid scaffold requires relatively harsh conditions during activation of carboxy-group, which may lead to decomposition of unstable oxylipins. Furthermore, additional protection-deprotection steps are required for oxylipins containing hydroxy-groups. In this work we describe synthesis of OxPLs containing oxylipins bound at the sn -2-position via an amide-bond that is characteristic of sphingophospholipids. Activation of oxylipins and attachment to the phospholipid scaffold are performed under mild conditions and characterized by high yield. Hydroxy-groups of oxylipins do not interfere with reactions and therefore no protection/deprotection steps are needed. In order to prevent oxylipin migration, a fatty acid residue at the sn -1 was bound through an alkyl bond, which is a common bond present in a large proportion of naturally occurring phospholipids. An additional advantage of combining alkyl and amide bonds in a single phospholipid molecule is that both types of bonds are phospholipase A 1 /A 2 -resistant, which may be expected to improve biological stability of OxPLs and thus simplify analysis of their effects. As proof of principle, several alkyl-amide oxidized phosphatidylcholines (OxPCs) containing either linear or prostane ring oxylipins have been synthesized. Importantly, we show here that alkyl-amide-OxPCs demonstrated biological activities similar to those of di-acyl-OxPCs. Alkyl-amide-OxPCs inhibited pro-inflammatory action of LPS and increased endothelial cellular barrier in vitro and in mouse models. The effects of alkyl-amide and di-acyl-OxPCs developed in a similar range of concentrations. We hypothesize that alkyl-amide-OxPLs may become a useful tool for deeper analysis of the structure-activity relationship of OxPLs. [Display omitted] • Simplified synthesis of alkyl-amide oxidized phospholipids (OxPLs) is described. • Alkyl-amide OxPLs inhibit action of LPS and enhance lung endothelial barrier. • Alkyl-amide OxPLs act similarly to diacyl-OxPLs in vitro and in vivo. • Alkyl-amide OxPLs are a practical tool for analysis of the biological role of OxPLs. [ABSTRACT FROM AUTHOR]

Epidemic models serve as a useful analytical tool to study how a disease behaves in a given population. Individual-level models (ILMs) can incorporate individual-level covariate information including spatial information, accounting for heterogeneity within the population. However, the high-level data required to parameterize an ILM may often be available only for a sub-population of a larger population (e.g., a given county, province, or country). As a result, parameter estimates may be affected by edge effects caused by infection originating from outside the observed population. Here, we look at how such edge effects can bias parameter estimates for within the context of spatial ILMs, and suggest a method to improve model fitting in the presence of edge effects when some global measure of epidemic severity is available from the unobserved part of the population. We apply our models to simulated data, as well as data from the UK 2001 foot-and-mouth disease epidemic. [ABSTRACT FROM AUTHOR]

The use of individually designed osteotomies, combined with individually manufactured osteosynthesis material, is rapidly becoming a standard for more challenging maxillofacial surgery. The benefits of patient-specific implants (PSI) in orthognathic surgery are clear in complex cases. PSIs can enhance precision and ease up the surgical protocol. We previously reported on the benefits of PSIs as reposition and fixation systems during Le Fort I osteotomy. The aim of this study was to evaluate a cohort of 28 patients, treated with bilateral sagittal split osteotomy (BSSO) and PSIs for fixation, with regard to healing for up to 3 years. A retrospective cohort of 48 patients with conventional mini-plate repositioned mandibles was also collected for statistical analysis. No statistically significant differences were found with regard to infection, soft tissue problems, or reoperations between these two groups. [ABSTRACT FROM AUTHOR]

Participation in outdoor cold-water swimming (OCWS) combines swimming exercise and low-temperature stimuli. Concerns have emerged about a potential risk of acute major adverse cardiac events during OCWS. We analysed the effect of prolonged OCWS on cardiac activity in trained athletes. We prospectively included swimmers performing OCWS qualifying for the English Channel Swim (Dinard, France, 2022). The swimming event consisted of laps over a 1000-m course, for up to 6 hours, in water at 15 °C. Core temperature (Tcore°) was monitored using an ingestible temperature sensor (e-Celsius, BodyCap) during and up to 1 hour after the swim. Body composition, 12-lead resting electrocardiogram (ECG), continuous 5-minute ECG recording, and echocardiography were assessed 1 day prior to the event and within the first hour after the end of the swim. Twenty participants (47.3 ± 8.6 years old, 11 males) were included. Mean body mass index was 27.1 ± 5.1 kg/m2 and fat mass was 25.2 ± 9.1%. Mean duration of swimming was 214 ± 115 minutes. Minimum Tcore was 35.6 ± 1.3 °C. Heart rate and blood pressure remained stable before and after exercise. QTc duration were higher after exercise (437.7 ± 27.7 vs. 457.2 ± 35.9 ms, P = 0.012), with 5 participants (3 males) exhibiting QTc > 480ms post-exercise. Two participants (10%) showed new onset premature ventricular contractions after exercise (<4 EBV during recording), none showed sustained arrythmia. Cardiac dimensions remained comparable before and after exercise, as well as left ventricular ejection fraction, global longitudinal strain, and diastolic parameters. Tricuspid annular plane systolic excursion (TAPSE) was significantly increased after exercise (21.3 ± 2.7 vs 25.3 ± 3.3 mm, P < 0.01). No correlation was observed between ΔQTc duration and anthropometric parameters (age, gender, fat mass), ΔTcore, nor exercise duration. Prolonged OCWS seemed to modify ventricular repolarization among trained swimmers without cardiac disease. However, post-exercise changes in QTc interval was not associated with an increased occurrence of cardiac arrhythmia nor alterations in cardiac function. Further analyses would be of interest to understand the implications of QT variation and its interaction with the autonomic nervous system adaptation. [ABSTRACT FROM AUTHOR]

Financial toxicity is a devastating outcome for patients with cancer and can impact their treatment adherence and health outcomes. One survey reveals that most radiation oncologists are "very concerned" with the negative impact treatment-related costs have on patients, and another survey found that more than 20 percent of patients experience financial toxicity related to their radiation therapy treatment. Financial advocates within cancer programs and practices can help mitigate patients' financial toxicity by supporting shared decision-making and helping with treatment cost planning. In 2022, ACCC set out to explore how financial advocates in radiation oncology provide financial navigation to patients with cancer and address the challenges they may face. Identify barriers to financial toxicity mitigation and treatment access challenges for patients with cancer undergoing radiation therapy. ACCC worked with an expert multidisciplinary Financial Advocacy Network Advisory Committee to conduct two, semi-structured discussion sessions on financial advocacy in radiation oncology. Prepared discussion topics included challenges and opportunities in delivering financial advocacy services, financial barriers to care and strategies to mitigate financial toxicity, and processes for prior authorizations and claim denials in the radiation oncology setting. Twenty-one participants attended the first session, and 17 participants attended the second session. Participants included financial navigators and counselors, oncology social workers, nurse navigators, and cancer program or practice administrators. Three major challenges emerged from both sessions: (1) Inadequate financial assistance from independent, charitable foundations to help pay for patients' deductibles, additional radiation treatment out-of-pocket costs, and care-related transportation costs. (2) Lack of best practices to handle prior authorization and avoid denials. (3) Lack of preparedness for changes imposed by the Radiation Oncology (RO) Model, which would impact care planning. Many cancer programs and practices have implemented financial advocacy services but remain restricted in the available assistance for radiation therapy patients. Radiation therapy represents a significant component of anti-cancer treatment and addressing the lack of financial support for patients is critical to improving patients' treatment adherence and health outcomes. Payment policies must be reformed to address complex prior authorization requirements and patients would benefit from greater financial support for radiation treatment and costs of wrap-around supportive services. [ABSTRACT FROM AUTHOR]