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Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide, driven by complex interactions among genetic, environmental, and lifestyle factors, with diet playing a pivotal role. Extra Virgin Olive Oil (EVOO), a cornerstone of the Mediterranean diet (MedDiet), is a plant-based fat that has garnered attention for its robust cardiovascular benefits, which are attributed to its unique composition of monounsaturated fatty acids (MUFAs), particularly oleic acid (OA); and bioactive polyphenols, such as Hydroxytyrosol (HT) and oleocanthal. These compounds collectively exert antioxidant, anti-inflammatory, vasodilatory, and lipid-modulating effects. Numerous clinical and preclinical studies have demonstrated that EVOO's properties reduce major modifiable cardiovascular risk factors, including hypertension, dyslipidemia, obesity, and type 2 diabetes. EVOO also promotes endothelial function by increasing nitric oxide (NO) bioavailability, thus favoring vasodilation, lowering blood pressure (BP), and supporting vascular integrity. Furthermore, it modulates biomarkers of cardiovascular health, such as C-reactive protein, low-density lipoprotein (LDL) cholesterol, and NT-proBNP, aligning with improved hemostatic balance and reduced arterial vulnerability. Emerging evidence highlights its interaction with gut microbiota, further augmenting its cardioprotective effects. This review synthesizes current evidence, elucidating EVOO's multifaceted mechanisms of action and therapeutic potential. Future directions emphasize the need for advanced extraction techniques, nutraceutical formulations, and personalized dietary recommendations to maximize its health benefits. EVOO represents a valuable addition to dietary strategies aimed at reducing the global burden of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Acute and chronic coronary artery disease (CAD) are interconnected, representing two facets of the same condition. Chronic CAD exhibits a dynamic nature, manifesting as stable or acute ischemia, or both. Myocardial ischemia can be transient and reversible. The genesis of CAD involves diverse anatomical and functional mechanisms, including endothelial dysfunction, arteriolar remodeling, capillary rarefaction, and perivascular fibrosis, though no single factor explains its heterogeneity. Chronic CAD is often stable but may present as symptomatic or asymptomatic (e.g., in diabetes) and affect various coronary compartments (epicardial or microcirculation). This complexity necessitates a reappraisal of our approach, as pathophysiological mechanisms vary and often overlap. A comprehensive exploration of these mechanisms using advanced diagnostic techniques can aid in identifying the dynamic processes underlying CAD. The disease may present as obstructive or non-obstructive, stable or unstable, underscoring its diversity. The primary source of CAD lies in the arterial wall, emphasizing the need for research on its components, such as the endothelium and vascular smooth muscle cells, and factors disrupting arterial homeostasis. Shifting focus from arterial luminal status to the arterial wall can provide insights into the genesis of atheromatous plaques, enabling earlier interventions to prevent their development and progression. [ABSTRACT FROM AUTHOR]

Biotoxins produced by harmful algal blooms (HABs) are a substantial global threat to ocean and human health. Domoic acid (DA) is one such biotoxin whose negative impacts are forecasted to increase with climate change and coastal development. This manuscript serves as a review of DA toxicosis after environmental exposure in humans and wildlife, including an introduction to HAB toxins, the history of DA toxicosis, DA production, toxicokinetic properties of DA, susceptibility, clinical signs, DA detection methods and other diagnostic tests, time course of toxicosis, treatment, prognostics, and recommendations for future research. Additionally, we highlight the utility of California sea lions (CSLs; Zalophus californianus) as a model and sentinel of environmental DA exposure. [ABSTRACT FROM AUTHOR]

Post-exertional malaise (PEM) is a defining condition of myalgic encephalomyelitis (ME/CFS). The concept requires that a provocation causes disabling limitation of cognitive and functional effort ("fatigue") that does not respond to rest. Cerebrospinal fluid was examined as a proxy for brain metabolite and lipid flux and to provide objective evidence of pathophysiological dysfunction. Two cohorts of ME/CFS and sedentary control subjects had lumbar punctures at baseline (non-exercise) or after submaximal exercise (post-exercise). Cerebrospinal fluid metabolites and lipids were quantified by targeted Biocrates mass spectrometry methods. Significant differences between ME/CFS and control, non-exercise vs. post-exercise, and by gender were examined by multivariate general linear regression and Bayesian regression methods. Differences were found at baseline between ME/CFS and control groups indicating disease-related pathologies, and between non-exercise and post-exercise groups implicating PEM-related pathologies. A new, novel finding was elevated serine and its derivatives sarcosine and phospholipids with a decrease in 5-methyltetrahydrofolate (5MTHF), which suggests general dysfunction of folate and one-carbon metabolism in ME/CFS. Exercise led to consumption of lipids in ME/CFS and controls while metabolites were consumed in ME/CFS but generated in controls. In general, the frequentist and Bayesian analyses generated complementary but not identical sets of analytes that matched the metabolic modules and pathway analysis. Cerebrospinal fluid is unique because it samples the choroid plexus, brain interstitial fluid, and cells of the brain parenchyma. The quantitative outcomes were placed into the context of the cell danger response hypothesis to explain shifts in serine and phospholipid synthesis; folate and one-carbon metabolism that affect sarcosine, creatine, purines, and thymidylate; aromatic and anaplerotic amino acids; glucose, TCA cycle, trans-aconitate, and coenzyme A in energy metabolism; and vitamin activities that may be altered by exertion. The metabolic and phospholipid profiles suggest the additional hypothesis that white matter dysfunction may contribute to the cognitive dysfunction in ME/CFS. [ABSTRACT FROM AUTHOR]

Background/Objectives: Cutaneous T-cell lymphoma (CTCL), including Mycosis fungoides (MF) and Sézary syndrome (SS), is a challenging-to-diagnose lymphoproliferative malignancy characterized by T-cell dysfunction and progressive cutaneous and extra cutaneous involvement. Disease severity assessment in CTCL is crucial for guiding treatment. This study aims to evaluate the interrater agreement and interrater reliability of mSWAT among dermatology residents and identify lesion types most prone to scoring variability. Methods: Sixteen dermatology residents with varied experience levels assessed 14 patients with confirmed MF/SS diagnoses. Using mSWAT, residents independently scored lesions severity on a standardized set of patient's photos. The results were compared with reference mSWAT scores provided by an experienced clinician. Descriptive statistics and the Shapiro–Wilk test were applied to evaluate data distributions, while Student's t-test assessed score deviations from reference values. Furthemore, we conducted a pilot the high frequency ultrasound (HFUS) study on a single patient, whose mSWAT score and photographs are also presented in the manuscript. Results: Significant discrepancies were observed in 64.29% of cases (9/14), with tumors and infiltrative lesions in erythrodermic SS patients posing particular scoring challenges. Misclassification of tumors as patches or plaques was a frequent issue, leading to underestimations in mSWAT scores. Residents' assessments of infiltrative lesions were also notably inconsistent. Conclusions: This study highlights significant interobserver variability in mSWAT scoring among less experienced dermatology residents, particularly with tumor and erythrodermic lesions. Findings underscore the need for enhanced training and standardized scoring protocols to improve mSWAT reliability. Similar to other comparable indices, such as PASI, the mSWAT should be employed consistently by the same physician during each assessment to systematically monitor and evaluate the skin condition of a patient under observation. However, broader application requires the acquisition of sufficient experience. The study suggests the use of the HFUS as an objective method of assessment of the skin lesion infiltration in MF/SS patients. [ABSTRACT FROM AUTHOR]

Background/objectives: Mycosis fungoides (MF) is a rare malignancy, with an indolent course in the early stages of the disease. However, due to major molecular and clinical heterogeneity, patients at an advanced stage of the disease have variable responses to treatment and considerably reduced life expectancy. Today, there is a lack of specific markers for the progression from early to advanced stages of the disease. To address these challenges, the non-interventional BIO-MUSE trial was initiated. Here, we report on a case study involving one patient, where combined omics analysis of tissue and blood was used to reveal the unique molecular features associated with the progression of the disease. Methods: We applied 10× genomics-based single-cell RNA sequencing to CD3+ peripheral T-cells, combined with T-cell receptor sequencing, to samples collected at multiple timepoints during the progression of the disease. In addition, GeoMx-based digital spatial profiling of T-helper (CD3+/CD8−), T-cytotoxic (CD3+/CD8+), and CD163+ cells was performed on skin biopsies. Results. The results pinpoint targets, such as transforming growth factor β1, as some of the mechanisms underlying disease progression, which may have the potential to improve patient prognostication and the development of precision medicine efforts. Conclusions: We propose that in patients with MF, the evolution of the malignant clone and the associated immune response need to be studied jointly to define relevant strategies for intervention. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic, recurrent and inflammatory skin disease. Although conventional immunosuppressants can ameliorate psoriatic symptoms, it tends to relapse over time. Previous studies have shown that exosomes from both immune and non-immune cells participate in psoriatic immunopathology. The biologically active cargoes in exosomes accelerate psoriasis progression by altering gene profiles and signaling pathways of neighboring cells. On the other hand, exosomes can be utilized as drug delivery platforms for psoriasis treatment. Especially, engineered exosomes may serve as drug delivery systems for effective delivery of proteins, nucleic acids or other drugs due to their low immunogenicity, good stability and ability to fuse with target cells. Therefore, investigation into the mechanisms underlying intercellular communications mediated by exosomes in skin lesions likely helps design drugs for therapy of psoriasis. In this review, we have summarized recent advances in the biogenesis of exosomes and their potential roles in the pathogenesis and treatment of psoriasis and further discussed their challenges and future directions in psoriasis treatment. In particular, this review highlights the immunoregulatory function of exosomes derived from immune or non-immune cells and exosome-based therapeutic applications in psoriasis, including their drug delivery systems. Thus, this review may help accelerate applications of exosomes for drug delivery and treatment of psoriasis. [ABSTRACT FROM AUTHOR]

Purpose: Teachers are important stakeholders in supporting children's physical literacy (PL), yet teachers' perception of PL assessment is underexplored. Method: Utilizing a mixed-methods design, 122 primary school teachers (of children aged 5–12 years) in Australia completed an online survey, followed by nine interviews. Results: Teachers who favored assessment (58%) tended to report assessing PL in children (χ2[1, N = 110] = 7.025, p =.008). Those who reported assessing PL (also 58%) were more confident to do so (χ2[2, N = 109] = 10.540, p =.005). Teachers considered movement skills, engagement and enjoyment, relationships, and safety and risk as the most important elements for assessing PL. Qualitative data showed nonsupport for PL assessment stemmed from skepticism regarding relevance of assessment, appropriateness of assessment, and views that the curriculum and PL framework were implicitly linked. Conclusion: Professional development, resources, and suitable PL teacher assessments can upskill teachers' knowledge, confidence, and reduce barriers in implementing PL assessments. [ABSTRACT FROM AUTHOR]

Background/Objectives: Right ventricular pacing is an effective and safe treatment option for patients experiencing symptomatic bradycardia. However, some individuals may develop left ventricular dysfunction as a consequence. Growth differentiation factor 15 (GDF-15), which is not present in a healthy adult heart, is upregulated in cardiomyocytes in response to various stress stimuli. This study aimed to explore the potential of GDF-15 as a biomarker for chronic right ventricular pacing. Methods: This single-center cross-sectional cohort study analyzed data from 265 consecutive patients (60.4% male) with either single- or dual-chamber pacemakers, all lacking pre-existing heart failure, who attended the outpatient department for routine follow-up. Chronic right ventricular (RV) pacing was defined as pacing exceeding 40% over the past year. Serum samples were collected, and GDF-15 levels were measured using a commercially available immunoassay (R&D Systems Inc., Minneapolis, MN, USA). Student's t-test was utilized to assess group differences, and receiver operating characteristic (ROC) analysis was employed to evaluate diagnostic performance. Results: When stratifying patients by pacing burden, GDF-15 levels were significantly higher in those with pacing over 40% compared to those with 40% or less (789 ± 293 pg/mL vs. 1186 ± 592 pg/mL; p < 0.001). The ROC analysis indicated that GDF-15 serves as a marker for chronic RV pacing, yielding an area under the curve of 0.713 (95% confidence interval 0.650–0.776; p < 0.001). Conclusions: This study suggests that GDF-15 may be a valuable biomarker for chronic right ventricular pacing. [ABSTRACT FROM AUTHOR]

Introduction: Orthostatic intolerance is highly prevalent in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and is caused by an abnormal reduction in cerebral blood flow (CBF). In healthy controls (HCs), the regulation of CBF is complex and cardiac output (CO) is an important determinant of CBF: a review showed that a 30% reduction in CO results in a 10% reduction in CBF. In previous and separate ME/CFS studies, we showed that CO and CBF decreased to a similar extent during tilt testing. The aim of the study: to test the relationship between CBF and CO, which seems to be abnormal in ME/CFS patients and is different from that in HCs. Methods: In this retrospective study we analyzed this relationship in a large group of patients. To compare the patient data with those of HCs, we focused on patients with a normal heart rate (HR) and blood pressure (BP) response to upright tilt. Also, the influence of clinical data was analyzed. A total of 534 ME/CFS patients and 49 HCs underwent tilt testing with measurements of HR, BP, CBF, CO, and end-tidal PCO2. To measure CBF, extracranial Doppler flow velocity and vessel diameters were obtained using a GE echo system. The same device was used to measure suprasternal aortic flow velocities. End-tidal PCO2 was recorded using a Nonin Lifesense device. Results: In 46 (9%) patients, CO and CBF changes were in the normal range for HCs, and in 488 (91%) an abnormal CO and CBF reduction was found. In patients with abnormal CO and CBF reductions, the slope of the regression line of CO versus CBF reduction was almost 1. The multiple regression analysis of the latter group showed that the CO reduction for the most part predicted the CBF reduction, with a limited role for the PETCO2 reduction. Conclusions: Two different patient groups with a normal HR and BP response during the tilt were identified: those with a CO and CBF in the normal range for HCs and those with an abnormal CO and CBF reduction during the tilt (91% of patients). In the latter group of patients, an almost 1:1 relationship between the CO and CBF reduction suggests the absence of compensatory vasodilation in the cerebral vasculature. This might indicate endothelial dysfunction in most ME/CFS patients and may have clinical and therapeutic implications. [ABSTRACT FROM AUTHOR]

Cannabichromene (CBC) is one of the main cannabinoids found in the cannabis plant, and although less well known than tetrahydrocannabinol (THC) and cannabidiol (CBD), it is gaining attention for its potential therapeutic benefits. To date, CBC's known mechanisms of action include anti-inflammatory, analgesic, antidepressant, antimicrobial, neuroprotective, and anti-acne effects through TRP channel activation and the inhibition of inflammatory pathways, suggesting that it may have therapeutic potential in the treatment of inflammatory skin diseases, such as atopic dermatitis (AD), but its exact mechanism of action remains unclear. Therefore, in this study, we investigated the effects of CBC on Th2 cytokines along with the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways involved in AD pathogenesis. We used a 2,4-Dinitrochlorobenzene (DNCB)-induced BALB/c mouse model to topically administer CBC (0.1 mg/kg or 1 mg/kg). The results showed that skin lesion severity, ear thickness, epithelial thickness of dorsal and ear skin, and mast cell infiltration were significantly reduced in the 0.1 mg/kg CBC-treated group compared with the DNCB-treated group (p < 0.001). In addition, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis showed a significant decrease in the mRNA expression of Th2 cytokines (TSLP, IL-4, IL-13) and inflammatory mediators (IFN-γ, IL-1β, IL-6, IL-17, IL-18, and IL-33) (p < 0.05). Western blot analysis also revealed a significant decrease in JAK1, JAK2, STAT1, STAT2, STAT3, and STAT6 protein expression (p < 0.05). These results suggest that CBC is a promising candidate for the treatment of AD and demonstrates the potential to alleviate AD symptoms by suppressing the Th2 immune response. [ABSTRACT FROM AUTHOR]

The increasing prevalence of both type 2 diabetes mellitus and heart failure has underscored the urgent need for optimized therapeutic strategies that address the complex interplay between these conditions. Dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as a popular class of glucose-lowering agents due to their favorable glycemic effects, safety profile, and potential cardiovascular benefits. However, the impact of DPP-4 inhibitors on heart failure outcomes in patients with diabetes remains contentious, with conflicting evidence from clinical trials and observational studies. This review critically examines current evidence on the use of DPP-4 inhibitors in patients with coexisting diabetes and heart failure, focusing on pharmacodynamics, safety, and efficacy outcomes. We explore the physiological mechanisms by which DPP-4 inhibitors may influence heart failure risk, including modulation of inflammation, oxidative stress, and myocardial fibrosis. Clinical trials such as SAVOR-TIMI 53, EXAMINE, and TECOS are evaluated to provide a comprehensive analysis of DPP-4 inhibitors' effects on hospitalization for heart failure, mortality, and cardiovascular events in diabetic patients. While some trials suggest an increased risk of HF hospitalizations with specific DPP-4 inhibitors (e.g., saxagliptin), others report neutral effects, raising questions about the class effects versus individual drug characteristics within this group. Additionally, we address discrepancies in outcomes related to patient demographics, HF phenotype, and comorbid conditions that may influence DPP-4 inhibitors' risk–benefit profile. Comparative insights into alternative glucose-lowering therapies such as SGLT2 inhibitors and GLP-1 receptor agonists are also provided, highlighting potential implications for treatment selection in this high-risk population. In summary, this review synthesizes available evidence on DPP-4 inhibitors' impact in diabetic patients with heart failure, aiming to guide clinicians in making informed therapeutic decisions. While DPP-4 inhibitors remain a viable option in diabetes management, caution is warranted in patients with advanced heart failure, and future research is essential to refine patient-specific guidelines. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory polygenic disease with significant impacts on skin and joints, leading to substantial treatment challenges and healthcare costs. The quest for novel therapeutic avenues has recently highlighted extracellular vesicles (EVs) due to their potential as biomarkers and therapeutic agents in autoimmune diseases, including psoriasis. EVs are nano-sized, lipid membrane-bound particles secreted by cells that have emerged as promising tools for targeted drug delivery, owing to their unique structure. This review delves into how EVs, either as mediators of cell communication or via their cargo (such as miRNA), directly participate in the pathology of psoriasis, influencing processes such as immune regulation, cell proliferation, and differentiation. Furthermore, this review explores the innovative application of EVs in psoriasis treatment, both as direct therapeutic agents and as vehicles for drug delivery, offering a novel approach to overcoming the current treatment limitations. [ABSTRACT FROM AUTHOR]

Pathogenic variants in KCNC3, which encodes the voltage-gated potassium channel Kv3.3, are associated with spinocerebellar ataxia type 13. SCA13 is a neurodegenerative disease characterized by ataxia, dysarthria and oculomotor dysfunction, often in combination with other signs and symptoms such as cognitive impairment. Known disease-causing variants are localized in the protein coding regions and predominantly in the transmembrane and voltage sensing domains. In a patient with an ataxic movement disorder and progressive cognitive decline, the c.-6C>A variant was detected in the Kozak sequence of KCNC3. The Kozak sequence is responsible for efficient initiation of translation. Functional analysis of the new c.-6C>A variant and the upstream 5'-UTR region of KCNC3 by luciferase assays, quantitative PCR and methylation analysis shows increased protein expression but no effect on transcription rate. Therefore, increased translation initiation of KCNC3 transcripts compared to wild-type Kozak sequence seems to be the cause of the increased expression. Variants in the regulatory elements of disease-causing genes probably play an underestimated role. [ABSTRACT FROM AUTHOR]

Simple Summary: This study focused on the potential role of non-invasive imaging diagnostic techniques, including LC-OCT, in the diagnosis of primary cutaneous lymphomas. Data from 40 lesions in 25 patients with a histological diagnosis of primary cutaneous lymphomas were retrospectively evaluated. Considering cutaneous T-cell lymphomas, RCM proved to be more effective than LC-OCT in detecting lymphocytes in the epidermis and dermis. As for B cell lymphomas, (25% of cases) mostly presented as nodules, with medium-reflective cell infiltration detected in 80% of cases by LC-OCT. This study suggests that non-invasive imaging could be valuable in supporting the diagnosis of primary cutaneous lymphomas, though further research is needed. Background/Objectives: Primary cutaneous lymphomas (PCL) are a heterogeneous group of non-Hodgkin lymphomas arising from malignant T (CTCL) or B (CBCL) cells, often mimicking other skin conditions. Recently, non-invasive diagnostic imaging modalities, including dermoscopy, Reflectance Confocal Microscopy (RCM), and Line-field Optical Coherence Tomography (LC-OCT), have become increasingly important, supporting clinicians in clinical practice. Hence, our study aimed to describe dermoscopic, RCM, and LC-OCT features of PCL and to explore their role in PCL management. Methods: Between December 2022 and January 2024, 40 lesions of 25 patients with PCL were retrospectively analyzed at the Dermatologic Unit of the University of Siena, Italy. Predefined dermoscopic, LC-OCT, and RCM criteria were assessed and their frequencies were calculated. Results: At dermoscopy, CTCL lesions were characterized by pinkish structureless areas (58,6%) and homogeneous distributed dotted vessels (35,7%), whereas 57.1% of CBCL presented with orange-yellow structureless areas. Considering CTCL, lymphocytes in the epidermis, dermal-epidermal junction, and dermis were detected by LC-OCT in 73.1%, 66.7%, and 51.9% and by RCM in 72.2%, 55.6%, and 61.1% of cases, respectively. The detection of lymphocytes was more precise using RCM than LC-OCT in CTCL (p < 0.001). Dermal infiltration of medium-reflective cells was visible in 80% and 40% of CBCL cases by LC-OCT and RCM, respectively. Conclusions: Non-invasive imaging techniques may support clinicians in managing PCL; however, further studies are mandatory in this field. [ABSTRACT FROM AUTHOR]

Background/Objectives: Many clinical trials have shown beneficial effects of low-dose dopamine on renal function, diuresis and symptom relief, or cardiac function in hospitalized patients with acute decompensated heart failure (HF). The aim is to assess the neurohormonal effects and the effects on clinical outcomes of the addition of low-dose dopamine in furosemide treatment in patients hospitalized for acute decompensated HF. Methods: A total of 62 patients hospitalized for acute decompensation of HF, were randomly allocated to one of the following three groups: i. LDF (low-dose furosemide), ii. HDF (high-dose furosemide) and, iii. LDFD (low-dose furosemide and dopamine). Primary outcomes of the present analysis were biochemical and neurohormonal indices (i.e., urea, creatinine, hemoglobin, electrolytes, natriuretic peptides, troponin, renin, angiotensin, aldosterone, adrenaline, noradrenaline). Secondary endpoints included clinical outcomes (i.e., length of stay, in-hospital mortality, 2-month mortality and rehospitalization, and 1-year mortality and rehospitalization). Results: Urea and creatinine levels were similar for each day among the three groups (p > 0.05). The amount of urine was similar among the three groups per measurement at 2, 4, 6 and at 8 h (p > 0.05). Biochemical and neurohormonal indices as well as clinical outcomes did not differ among patients receiving different doses of furosemide, nor in patients receiving furosemide in combination with dopamine (p > 0.05). Conclusions: Although the addition of low-dose dopamine to intravenous furosemide was considered to have some theoretical advantages in maintaining renal function, no significant differences in neurohormonal effects and clinical outcomes were observed in patients hospitalized for acute decompensation of HF. [ABSTRACT FROM AUTHOR]

Aim: This study explored whether hospitals that allocate greater resources to their nursing staff provide better healthcare services than those that invest less in their nursing personnel. Design: Cross‐sectional logistic and tobit analyses. Methods: We examined a sample of 314 California hospitals in 2017. We obtained a hospital's public recognition for treating nurses fairly between 2015 and 2017 from Nurse.org, the largest online community of nurses. We derived a hospital's healthcare quality in 2018 from the 2019–2020 Best Hospitals rankings released by U.S. News, a well‐known media company publishing independent healthcare assessments periodically. Results: Our results showed that a nurse‐friendly workplace was a crucial determinant of its overall healthcare quality. Conclusion and implications: Healthcare administrators keen to enhance the quality of healthcare services should consider creating nurse‐friendly workplaces. Furthermore, their evaluation of nurses' contributions to overall healthcare quality should not solely depend on the nurse‐assessed quality of care, but rather comprise not only broad aspects of patient outcomes in primary care but also patient experiences, care‐related factors and expert opinions. Patient or public contribution: Our study helped address the overwhelmed healthcare system, whose long‐running shortage of nurses has been exacerbated by the COVID‐19 pandemic. Our work suggested that a hospital's investment in a nurse‐friendly workplace can enhance its acquisition, retention and devotion of the nursing staff. This, in turn, can have profound impacts on its overall healthcare quality. What already is known: Existing empirical evidence on the relation between nurse‐friendly workplace and healthcare quality is limited and inconclusive. What this paper adds: We documented evidence that the quality of healthcare services provided by hospitals varies with their treatment of nursing staff. Implications for practice/policy: Our results provided insights into key policies that have the potential to improve healthcare quality. [ABSTRACT FROM AUTHOR]

Percutaneous coronary intervention (PCI) to chronic total occlusion (CTO) is still a subject of debate. The primary goal of revascularization is to provide symptomatic relief and enhance left ventricular (LV) functions. Global longitudinal strain (GLS) is proven to be more sensitive than the ejection fraction (EF), especially for subtle ischemic changes. The purpose of this study was to investigate the improvement in LV GLS after revascularization of symptomatic stable coronary patients with single-vessel CTO, categorized according to their collateral supply grades. Sixty-nine patients with successful CTO-PCI were grouped, according to their collateral supply grades, as well-developed (WD) and poor collateral groups and followed-up for 3 months. Basal characteristics were similar for both groups, except for a lower EF (p = 0.04) and impaired GLS (p < 0.0001) in the poor collateral group. At the end of 3 months follow-up, symptomatic relief was similar in both groups (p = 0.101). GLS improvement reached statistical significance only for the poor collateral, not for the WD group (p < 0.0001 and p = 0.054, respectively). The EF did not change significantly in both groups. Poorly collateralized CTO lesions may not only result in baseline LV dysfunction, but also appear to carry potential for recovery after revascularization. This may not be the case for WD collaterals. [ABSTRACT FROM AUTHOR]

Cardiorenal syndrome (CRS) is a life-threatening disorder that involves a complex interplay between the two organs. Managing this multifaceted syndrome is challenging in the hospital and requires a multidisciplinary approach to tackle the many manifestations and complications. There is no universally accepted algorithm to treat patients, and therapeutic options vary from one patient to another. The mainstays of therapy involve the stabilization of hemodynamics, decongestion using diuretics or renal replacement therapy, improvement of cardiac output with inotropes, and goal-directed medical treatment with renin–angiotensin–aldosterone system inhibitors, beta-blockers, and other medications. Mechanical circulatory support is another viable option in the armamentarium of agents that improve symptoms in select patients. [ABSTRACT FROM AUTHOR]

Background: Coronary computed tomographic angiography (CCTA) is a non-invasive imaging technique that possesses the ability to provide detailed anatomical information about coronary arteries, avoiding unnecessary invasive procedures. Our aim was to assess the ability of CCTA to identify coronary artery disease compared to invasive coronary angiography (ICA) in a real-life setting. Methods: We examined 137 consecutive patients who underwent ICA after CCTA. The latter was conducted in various non-selected centers, and data regarding stenosis were taken from individual reports without further analysis. Results: A total of 60.5% of patients who underwent CCTA were found to have at least one critical stenosis, while the remaining 39.5% underwent ICA due to concurrent clinical or instrumental indications. Among these, 29.5% had angiographically critical pathology, 20.3% underwent a percutaneous coronary intervention (PCI), and 1.8% had coronary artery bypass grafting. Among the 83 patients with positive CCTA results, 34.9% had negative ICA findings. CCTA demonstrated low sensitivity (57.8%) and a positive predictive value of 42.6%. However, it retained high specificity (83.6%) and a negative predictive value of 90.4% for identifying critical stenosis. Among the 18.2% of patients who underwent CCTA without a specific indication, 60% had critical coronary lesions on their ICA and 86.6% of these subsequently underwent a PCI. Conclusions: CCTA performed in non-selective centers has a low concordance with ICA. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a metabolic disorder that has alarmingly increased in incidence in recent decades. One of the most serious complications of T2DM is diabetic cardiomyopathy (DCM), an often underrecognized yet severe condition that is a leading cause of mortality among diabetic patients. In the early stages of DCM, patients typically show no symptoms and maintain normal systolic and diastolic left ventricle function, making early detection challenging. Currently available clinical markers are often not specific enough to detect the early stage of DCM. Conventional biomarkers of cardiac mechanical stress and injury, such as natriuretic peptides (NPs) and cardiac troponin I (cTnI), have shown limited predictive value for patients with T2DM. NPs have proven efficacy in detecting diastolic dysfunction in diabetic patients when used alongside 2D echocardiography, but their utility as biomarkers is limited to symptomatic individuals. While cTnI is a reliable indicator of general cardiac damage, it is not specific to cardiac injury caused by high glucose levels or T2DM. This underscores the need for research into biomarkers that can enable early diagnosis and management of DCM to reduce mortality rates. Promising novel biomarkers that showed good performance in detecting diastolic dysfunction or heart failure in diabetic patients include galectin-3, ST2, FGF-21, IGFBP-7, GDF-15, and TGF-β. This review summarizes the current understanding of DCM biomarkers, aiming to generate new ideas for the early recognition and treatment of DCM by exploring related pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

(1): Atopic dermatitis and psoriasis vulgaris are chronic, inflammatory diseases. Clinical presentation usually leads to a proper diagnosis, but sometimes neither clinical examination nor histopathological evaluation can be conclusive. Therefore, we aimed to build up a novel diagnostic tool and check it for accuracy. The main objective of our work was to differentiate between healthy skin (C), atopic dermatitis (AD) and psoriasis vulgaris (PV) biopsies on the base of involucrin (IVL) and human β-defensin-2 (hBD-2) concentrations and their mRNA, as well as mRNA for TPP2 and PSMB8. (2): ELISA for IVL and hBD-2 proteins and Real-time PCR for the relative expression of mRNA for: IVL (IVL mRNA), hBD-2 (hBD-2 mRNA), PSMB8 (PSMB8 mRNA) and TPP2 (TPP2 mRNA), isolated from skin biopsies taken from AD and PV patients and healthy volunteers were performed. (3): hBD-2 mRNA and PSMB8 mRNA correlated with some parameters of clinical assessment of inflammatory disease severity. hBD-2 mRNA expression, exclusively, was sufficient to distinguish inflammatory skin biopsies from the healthy ones. (4): hBD-2 mRNA and PSMB8 mRNA analysis were the most valuable parameters in differentiating AD and PV biopsies. [ABSTRACT FROM AUTHOR]

Background/Objectives: Non-vitamin K antagonist oral anticoagulants (NOACs) have demonstrated similar effectiveness and safety profiles to vitamin K antagonists (VKAs) in treating nonvalvular atrial fibrillation (AF). Given their favorable pharmacological profile, including the rapid onset and offset of action, fixed dosing, and predictable pharmacokinetics with a consistent dose-response relationship, reducing the need for frequent blood tests, researchers have investigated the potential of NOACs in patients with AF and valvular heart disease (VHD). Methods: Clinical trials, excluding patients with mechanical prosthetic valves or moderate/severe mitral stenosis, have shown the benefits of NOACs over VKAs in this population. However, there is a need for further research to determine if these findings apply to mechanical valve prostheses and NOACs. Results: Several ongoing randomized controlled trials are underway to provide more definitive evidence regarding NOAC treatment in moderate to severe rheumatic mitral stenosis. Importantly, recent trials that included patients with atrial fibrillation and bioprosthetic valves (also transcatheter heart valves) have provided evidence supporting the safety of NOACs in this specific patient population. Ongoing research aims to clearly define the specific scenarios where NOACs can be safely and effectively prescribed for various types of VHD, including moderate/severe mitral stenosis and mechanical valves. Conclusions: The aim of this review is to accurately identify the specific situations in which NOACs can be prescribed in patients with VHD, with a focus centered on each type of valvulopathy. [ABSTRACT FROM AUTHOR]

Background: Coronary artery bypass grafting remains the standard of care for advanced and multifocal coronary artery disease; however, for patients that are surgical candidates, total arterial revascularization (TAR) remains underutilized due to concerns such as sternal wound infections and the learning curve. We present the results of a large cohort of mid-career surgeons transitioning to TAR, focusing on short-term outcomes and the learning curve. Methods: The surgeons transitioned to using TAR as the preferred revascularization technique in August of 2017. The Society of Thoracic Surgeons database was reviewed to identify all patients who underwent isolated non-emergent CABG performed by a single surgeon from January 2014 through January 2022. Patients were divided into two groups—those who had TAR and those who had traditional CABG using one internal mammary artery and vein grafts (IMA-SVG). Results: Eight hundred ninety-eight patients meet inclusion criteria (458 IMA-SVG and 440 TAR). The TAR group had slightly longer cardiopulmonary bypass time, cross clamp times, and operative times (all p < 0.05); however, ICU stay was shorter and 30-day readmission rate was lower for TAR compared to IMA-SVG (all p < 0.05). The TAR group also required fewer postoperative transfusions (p = 0.005). There was no difference in prolonged intubation, stroke, length of stay, mortality, or sternal wound complications between groups (all p > 0.05). The average TAR was 30 min longer; however, learning curves, stratified by number of grafts placed, showed no significant learning curve associated with TAR. Conclusions: An experienced surgeon transitioning from IMA-SVG to TAR slightly increases operative time, but decreases ICU stay, readmissions, and postoperative transfusions with no significant difference in rates of immediate post-operative complications or 30-day mortality, with a minimal learning curve. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) represents a complex clinical syndrome, often very difficult to diagnose using the available tools. As the global burden of this disease is constantly growing, surpassing the prevalence of heart failure with reduced ejection fraction, during the last few years, efforts have focused on optimizing the diagnostic and prognostic pathways using an immense panel of circulating biomarkers. After the paradigm of HFpEF development emerged more than 10 years ago, suggesting the impact of multiple comorbidities on myocardial structure and function, several phenotypes of HFpEF have been characterized, with an attempt to find an ideal biomarker for each distinct pathophysiological pathway. Acknowledging the limitations of natriuretic peptides, hundreds of potential biomarkers have been evaluated, some of them demonstrating encouraging results. Among these, soluble suppression of tumorigenesis-2 reflecting myocardial remodeling, growth differentiation factor 15 as a marker of inflammation and albuminuria as a result of kidney dysfunction or, more recently, several circulating microRNAs have proved their incremental value. As the number of emerging biomarkers in HFpEF is rapidly expanding, in this review, we aim to explore the most promising available biomarkers linked to key pathophysiological mechanisms in HFpEF, outlining their utility for diagnosis, risk stratification and population screening, as well as their limitations. [ABSTRACT FROM AUTHOR]

Congestion and fluid retention are the hallmarks of decompensated heart failure and the major reason for the hospitalization of patients with heart failure. Diuretics have been used in heart failure for decades, and they remain the backbone of the contemporary management of heart failure. Loop diuretics is the preferred diuretic, and it has been given a class I recommendation by clinical guidelines for the relief of congestion symptoms. Although loop diuretics have been used virtually among all patients with acute decompensated heart failure, there is still very limited clinical evidence to guide the optimized diuretics use. This is a sharp contrast to the rapidly growing evidence of the rest of the guideline-directed medical therapy of heart failure and calls for further studies. The loop diuretics possess a unique pharmacology and pharmacokinetics that lay the ground for different strategies to increase diuretic efficiency. However, many of these approaches have not been evaluated in randomized clinical trials. In recent years, a stepped and protocolized diuretics dosing has been suggested to have superior benefits over an individual clinician-based strategy. Diuretic resistance has been a major challenge to decongestion therapy for patients with heart failure and is associated with a poor clinical prognosis. Recently, therapy options have emerged to help overcome diuretic resistance to loop diuretics and have been evaluated in randomized clinical trials. In this review, we aim to provide a comprehensive review of the pharmacology and clinical use of loop diuretics in the context of heart failure, with attention to its side effects, and adjuncts, as well as the challenges and future direction. [ABSTRACT FROM AUTHOR]

Managing health care for older adults aged 75 years and older can pose unique challenges stemming from age-related physiological differences and comorbidities, along with elevated risk of delirium, frailty, disability, and polypharmacy. This review is aimed at providing a comprehensive analysis of the management of acute coronary syndromes (ACS) in older patients, a demographic substantially underrepresented in major clinical trials. Because older patients often exhibit atypical ACS symptoms, a nuanced diagnostic and risk stratification approach is necessary. We aim to address diagnostic challenges for older populations and highlight the diminished sensitivity of traditional symptoms with age, and the importance of biomarkers and imaging techniques tailored for older patients. Additionally, we review the efficacy and safety of pharmacological agents for ACS management in older people, emphasizing the need for a personalized and shared decision-making approach to treatment. This review also explores revascularization strategies, considering the implications of invasive procedures in older people, and weighing the potential benefits against the heightened procedural risks, particularly with surgical revascularization techniques. We explore the perioperative management of older patients experiencing myocardial infarction in the setting of noncardiac surgeries, including preoperative risk stratification and postoperative care considerations. Furthermore, we highlight the critical role of a multidisciplinary approach involving cardiologists, geriatricians, general and internal medicine physicians, primary care physicians, and allied health, to ensure a holistic care pathway in this patient cohort. [ABSTRACT FROM AUTHOR]

Altered ankyrin-R (AnkR; encoded by ANK1) expression is associated with diastolic function, left ventricular remodeling, and heart failure with preserved ejection fraction (HFpEF). First identified in erythrocytes, the role of AnkR in other tissues, particularly the heart, is less studied. Here, we identified the expression of both canonical and small isoforms of AnkR in the mouse myocardium. We demonstrate that cardiac myocytes primarily express small AnkR (sAnkR), whereas cardiac fibroblasts predominantly express canonical AnkR. As canonical AnkR expression in cardiac fibroblasts is unstudied, we focused on expression and localization in these cells. AnkR is expressed in both the perinuclear and cytoplasmic regions of fibroblasts with considerable overlap with the trans-Golgi network protein 38, TGN38, suggesting a potential role in trafficking. To study the role of AnkR in fibroblasts, we generated mice lacking AnkR in activated fibroblasts (Ank1-ifKO mice). Notably, Ank1-ifKO mice fibroblasts displayed reduced collagen compaction, supportive of a novel role of AnkR in normal fibroblast function. At the whole animal level, in response to a heart failure model, Ank1-ifKO mice displayed an increase in fibrosis and T-wave inversion compared with littermate controls, while preserving cardiac ejection fraction. Collagen type I fibers were decreased in the Ank1-ifKO mice, suggesting a novel function of AnkR in the maturation of collagen fibers. In summary, our findings illustrate the novel expression of AnkR in cardiac fibroblasts and a potential role in cardiac function in response to stress. [ABSTRACT FROM AUTHOR]

Long COVID is a common sequela of SARS-CoV-2 infection. Data from numerous scientific studies indicate that long COVID involves a complex interaction between pathophysiological processes. Long COVID may involve the development of new diagnosable health conditions and exacerbation of pre-existing health conditions. However, despite this rapidly accumulating body of evidence regarding the pathobiology of long COVID, psychogenic and functional interpretations of the illness presentation continue to be endorsed by some healthcare professionals, creating confusion and inappropriate diagnostic and therapeutic pathways for people living with long COVID. The purpose of this perspective is to present a clinical and scientific rationale for why long COVID should not be considered as a functional neurologic disorder. It will begin by discussing the parallel historical development of pathobiological and psychosomatic/sociogenic diagnostic constructs arising from a common root in neurasthenia, which has resulted in the collective understandings of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and functional neurologic disorder (FND), respectively. We will also review the case definition criteria for FND and the distinguishing clinical and neuroimaging findings in FND vs. long COVID. We conclude that considering long COVID as FND is inappropriate based on differentiating pathophysiologic mechanisms and distinguishing clinical findings. [ABSTRACT FROM AUTHOR]

This study investigated the effects of certain roselle (Hibiscus sabdariffa Linnaeus) extraction methods on various functional properties, including the antioxidant and antiglycation capacities and bacterial growth inhibition. Roselle anthocyanins were extracted using water and ethanol solvents at different temperatures and concentrations. The results revealed that the extraction rate increased with higher temperatures and ethanol concentrations (p < 0.05). Ethanol extracts exhibited higher total organic acid and total anthocyanin contents compared to water extracts, while water extracts showed higher total saccharide, total polyphenol, and total flavonoid contents (p < 0.05). Furthermore, the water extracts demonstrated superior Trolox equivalent antioxidant capacity (TEAC) values, while the ethanol extracts exhibited better 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability, antiglycation capacity, and bacterial growth inhibition. A Pearson correlation analysis revealed strong associations between specific components and functional properties, such as a positive correlation between the total anthocyanin content and antiglycation capacity (R2 = 0.9862). A principal component analysis and agglomerative hierarchical clustering highlighted distinct clusters of water and ethanol extracts, indicating solvent-dependent variations in functional properties. This study assessed roselle extraction models for antioxidant, antiglycation, and antibacterial activities, which could be used for the development of functional alcoholic or non-alcoholic beverages. [ABSTRACT FROM AUTHOR]

Kudzu root (Puerariae lobatae Radix) is the tuberous root of Pueraria lobata, family Leguminosae. Kudzu root contains a variety of beneficial active ingredients such as puerarin, daidzin, daidzein, genistenin, 3′-hydroxy puerarin, β-sitosterol, stigmasterol, arachidic acid, and so on. Modern medical research shows that active ingredients in kudzu root are widely used clinically as raw materials for the treatment of hyperglycemia, non-alcoholic fatty liver disease, myocardial infarction, alcohol addiction, oxidative stress, inflammatory response, and retinal blockage due to their various pharmacological effects such as improving cardiovascular circulation, lowering blood lipids, lowering blood pressure, lowering blood sugar, being antipyretic, being estrogen-like, and relieving alcohol. China has rich resources of kudzu root, and active ingredients are usually extracted before it is made into a preparation, so whether the extraction and separation process is reasonable will directly affect the ease of preparation and the efficacy of the treatment. This paper reviews the process methods for the extraction and separation of active ingredients in kudzu root and its common pharmacological activities. The aim is to provide some references for readers to compare the advantages and disadvantages of various extraction and separation methods as well as understand the active ingredients and pharmacological activities of kudzu root. [ABSTRACT FROM AUTHOR]

Interleukin-5 functions as a B-cell differentiation factor, but more importantly, in the context of this review, it plays a variety of roles in eosinophil biology, including eosinophil differentiation and maturation in the bone marrow, and facilitates eosinophil migration to tissue sites, usually in the context of an allergic reaction. Given the availability of selective anti-IL-5 drugs such as mepolizumab and reslizumab, as well as the IL-5 receptor antagonist benralizumab, it is worth investigating whether they could be used in some cases of allergic disease. Asthma has a well-documented involvement of IL-5 in its pathophysiology and has clear benefits in the case of anti-IL-5 therapy; therefore, current knowledge is presented to provide a reference point for the study of less-described diseases such as atopic dermatitis, chronic rhinosinusitis, chronic spontaneous urticaria, and its association with both IL-5 and anti-IL-5 treatment options. We then review the current literature on these diseases, explain where appropriate potential reasons why anti-IL-5 treatments are ineffective, and then point out possible future directions for further research. [ABSTRACT FROM AUTHOR]

The detrimental effects of ultraviolet radiation (UVR) on human skin are well-documented, encompassing DNA damage, oxidative stress, and an increased risk of carcinogenesis. Conventional photoprotective measures predominantly rely on filters, which scatter or absorb UV radiation, yet fail to address the cellular damage incurred post-exposure. To fill this gap, antioxidant molecules and DNA–repair enzymes have been extensively researched, offering a paradigm shift towards active photoprotection capable of both preventing and reversing UV–induced damage. In the current review, we focused on "active photoprotection", assessing the state-of-the-art, latest advancements and scientific data from clinical trials and in vivo models concerning the use of DNA-repair enzymes and naturally occurring antioxidant molecules. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to explore primary teachers' perspectives of implementing cooperative learning (CL) to accomplish social and emotional learning (SEL) in Aotearoa New Zealand physical education. Method: A qualitative case study design gathered data from 21 teachers at four primary schools using interviews, focus groups, and field notes. Inductive and deductive analysis were used for data analysis. Findings: Four primary themes are presented: emotional processes, social and interpersonal skills, students working it out, and taking time. Findings show that using CL as a pedagogical approach allowed teachers to teach for and accomplish SEL outcomes while accomplishing broader learning outcomes in physical education. However, there appeared to be shortcomings and constraints in the implementation of CL to accomplish SEL outcomes comprehensively. Conclusion: Future research should look to examine and connect professional learning involving pedagogical approaches like CL in physical education to SEL theory and school settings to enhance learning. [ABSTRACT FROM AUTHOR]

Grape marc is a by-product resulting from the winemaking industry that still contains beneficial compounds that can be valorized. Thus, we report here the possibility of using polyphenolic extracts of grape marc origin to obtain sun protection creams. The extractions were performed in ethanol and acetone solutions using pomace from different grape varieties (Merlot, Bläufrankisch, Fetească Neagră, Isabella) as a raw material. The obtained extracts were analyzed in order to determine the total phenolic content, the antioxidant activity, and the sun protection factor (SPF) via Mansur spectrophotometric assay. The best results were achieved using 70% ethanol in water as a solvent. The extracts with the highest potential photoprotective effects are from the Merlot variety (SPFspectrophotometric = 7.83 ± 0.76). The sunscreens were prepared using the 70% ethanolic extract of the Merlot variety evaporated to dryness, redissolved in either distilled water or ethanol. The SPF estimated in vitro via the COLIPA method showed values of 14.07 ± 1.50 and 11.46 ± 1.32 for the aqueous and ethanolic extracts, respectively, when working with a cream to polyphenolic extract a ratio of 1/1 (w/w). At the same time, the use of aqueous polyphenolic extracts ensures the better stability of creams compared with the ethanolic ones. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is a cluster of metabolic abnormalities affecting ~25% of adults and is linked to chronic diseases such as cardiovascular disease, cancer, and neurodegenerative diseases. Oxidative stress and inflammation are key drivers of MetS. Hesperidin, a citrus bioflavonoid, has demonstrated antioxidant and anti-inflammatory properties; however, its effects on MetS are not fully established. We aimed to determine the optimal dose of hesperidin required to improve oxidative stress, systemic inflammation, and glycemic control in a novel mouse model of MetS. Male 5-week-old C57BL/6 mice were fed a high-fat, high-salt, high-sugar diet (HFSS; 42% kcal fat content in food and drinking water with 0.9% saline and 10% high fructose corn syrup) for 16 weeks. After 6 weeks of HFSS, mice were randomly allocated to either the placebo group or low- (70 mg/kg/day), mid- (140 mg/kg/day), or high-dose (280 mg/kg/day) hesperidin supplementation for 12 weeks. The HFSS diet induced significant metabolic disturbances. HFSS + placebo mice gained almost twice the weight of control mice (p < 0.0001). Fasting blood glucose (FBG) increased by 40% (p < 0.0001), plasma insulin by 100% (p < 0.05), and HOMA-IR by 150% (p < 0.0004), indicating insulin resistance. Hesperidin supplementation reduced plasma insulin by 40% at 140 mg/kg/day (p < 0.0001) and 50% at 280 mg/kg/day (p < 0.005). HOMA-IR decreased by 45% at both doses (p < 0.0001). Plasma hesperidin levels significantly increased in all hesperidin groups (p < 0.0001). Oxidative stress, measured by 8-OHdG, was increased by 40% in HFSS diet mice (p < 0.001) and reduced by 20% with all hesperidin doses (p < 0.005). In conclusion, hesperidin supplementation reduced insulin resistance and oxidative stress in HFSS-fed mice, demonstrating its dose-dependent therapeutic potential in MetS. [ABSTRACT FROM AUTHOR]

This review explores the intricacies of evaluating cirrhotic patients for liver resection while exploring how to extend surgical intervention to those typically excluded by the Barcelona Clinic Liver Cancer (BCLC) criteria guidelines by focusing on the need for robust preoperative assessment and innovative surgical strategies. Cirrhosis presents unique challenges and complicates liver resection due to the altered physiology of the liver, portal hypertension, and liver decompensation. The primary objective of this review is to discuss the current approaches in assessing the suitability of cirrhotic patients for liver resection and aims to identify which patients outside of the BCLC criteria can safely undergo liver resection by highlighting emerging strategies that can improve surgical safety and outcomes. [ABSTRACT FROM AUTHOR]

Extracorporeal photopheresis (ECP) is a therapeutic modality used for T-cell-mediated disorders. This approach involves exposing isolated white blood cells to photoactivatable 8-methoxypsoralen (8-MOP) and UVA light, aiming to induce apoptosis in T-cells and thereby modulate immune responses. However, conventional 8-MOP-ECP lacks cell selectivity, killing both healthy and diseased cells, and has shown limited treatment efficacy. An alternative approach under investigation involves the use of 5-aminolevulinic acid (ALA) in conjunction with light, referred to as ALA-based photodynamic therapy. Our previous ex vivo studies suggest that ALA-ECP exhibits greater selectivity and efficiency in killing T-cells derived from patients with T-cell-mediated disorders compared to those treated with 8-MOP-ECP. We have conducted a clinical phase I–(II) study evaluating ALA-ECP safety and tolerability in cutaneous T-cell lymphoma (CTCL). Here, 20 ALA-ECP treatments were administered to one CTCL patient, revealing no significant changes in vital signs. Two adverse events were reported; both evaluated by the Internal Safety Review Committee as non-serious. In addition, five conceivable events with mainly mild symptoms took place. During the study period, a 53% reduction in skin involvement and a 50% reduction in pruritus was observed. In conclusion, the results indicate that ALA-ECP treatment is safe and well tolerated. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common dermatological disease affecting both children and adults. No drug-free emulgel has been developed and studied in vitro and in vivo for the treatment of AD. The aim of this study was to develop and assess the efficacy of a topical emulgel containing hyaluronic acid, glycerol, Calendula officinalis, Aloe vera, polyphenols and EGF for the concomitant treatment in patients with AD aged over 14. Objective skin barrier function parameters were included, such as transepidermal water loss (TEWL), skin temperature, pH, stratum corneum hydration, skin elasticity and erythema. The subjective opinion of the patients was determined including acceptability, absorption, comfort of use and tolerability, as well as the degree of improvement in patients' quality of life. We observed an improvement in the subjective parameters studied and statistically significant differences in the objective parameters. Specifically, we found an improvement in TEWL (p = 0.006), erythema (p = 0.008) and hydration (p < 0.001), parameters indicating an improvement in the epidermal barrier. One hundred per cent of patients were satisfied with the product. Therefore, these results suggest that the product may contribute to the treatment of AD. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, with an increasing number of targeted therapies available. While biologics to treat AD exclusively target the key cytokines of type 2 immunity, Janus kinase inhibitors target a broad variety of cytokines, including IFN-γ. To better stratify patients for optimal treatment outcomes, the identification and characterization of subgroups, especially with regard to their IFNG expression, is of great relevance, as the role of IFNG in AD has not yet been fully clarified. This study aims to define AD subgroups based on their lesional IFNG expression and to characterize them based on their gene expression, T cell secretome and clinical attributes. RNA from the lesional and non-lesional biopsies of 48 AD patients was analyzed by RNA sequencing. Based on IFNG gene expression and the release of IFN-γ by lesional T cells, this cohort was categorized into three IFNG groups (high, medium, and low) using unsupervised clustering. The low IFNG group showed features of extrinsic AD with a higher prevalence of atopic comorbidities and impaired epidermal lipid synthesis. In contrast, patients in the high IFNG group had a higher average age and an activation of additional pro-inflammatory pathways. On the cellular level, higher amounts of M1 macrophages and natural killer cell signaling were detected in the high IFNG group compared to the low IFNG group by a deconvolution algorithm. However, both groups shared a common dupilumab response gene signature, indicating that type 2 immunity is the dominant immune shift in both subgroups. In summary, high and low IFNG subgroups correspond to intrinsic and extrinsic AD classifications and might be considered in the future for evaluating therapeutic efficacy or non-responders. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated a new imaging technique called ex vivo confocal microscopy to examine rare skin conditions. By analyzing tissue samples from different skin disorders, we found that this technique could accurately identify unique microscopic features of both common and rare skin diseases. Importantly, examiners with more experience in interpreting these images achieved higher accuracy in diagnosis. This suggests that ex vivo confocal microscopy has the potential to be a valuable tool alongside traditional methods for diagnosing rare skin conditions early and accurately, leading to better treatment outcomes for patients. While ex vivo confocal laser scanning microscopy has previously demonstrated its utility in most common skin diseases, its use in the assessment of dermatological entities with lower incidence remains unexplored in most cases. We therefore aimed to evaluate the diagnostic efficacy of some rare skin tumors as well as a few inflammatory skin diseases, that have not yet been studied in ex vivo confocal laser scanning microscopy. A total of 50 tissue samples comprising 10 healthy controls, 10 basal cell carcinoma, 10 squamous cell carcinoma, and 20 rare skin conditions were imaged using the newest generation ex vivo confocal microscopy (Vivascope 2500 M-G4, Vivascope GmbH, Munich, Germany). Three blinded investigators were asked to identify characteristic features of rare skin disorders and distinguish them from more common skin diseases in the ex vivo confocal microscopy images. Our findings present the capability of ex vivo confocal microscopy to display distinctive morphologic patterns in common and rare skin diseases. As might be expected, we found a strong correlation between imaging experience and diagnostic accuracy. While the imaging inexperienced dermatohistopathologist reached 60% concordance, the imaging-trained dermatologist obtained 88% agreement with dermatohistopathology. The imaging-trained dermatohistopathologist achieved concordance up to 92% with gold-standard dermatohistopathology. This study highlights the potential of ex vivo confocal laser scanning microscopy as a promising adjunct to conventional dermatohistopathology for the early and precise identification of rare dermatological disorders. [ABSTRACT FROM AUTHOR]

Biologics are widely used to treat moderate-to-severe psoriasis. However, we have unmet needs for predicting individual patient responses to biologics before starting psoriasis treatment. We investigate a reliable platform and biomarkers for predicting individual patient responses to biologics. In a cohort study between 2018 and 2023 from a referral center in Taiwan, twenty psoriasis patients with or without psoriatic arthritis who had ever experienced two or more biologics were enrolled. Peripheral blood mononuclear cells obtained from these patients were treated with Streptococcus pyogenes and different biologics. The PASI reduction rate was strongly correlated with the reduction rate in the IL-13 level (p = 0.001) and the ratios of IFN-γ to IL-13 (p < 0.001), IFN-γ to IL-4 (p = 0.019), and IL-17A to IL-13 (p = 0.001). The PASI reduction difference was strongly correlated with the difference in the IFN-γ level (p = 0.002), the difference in the ratios of IFN-γ to IL-4 (p = 0.041), the difference in the ratios of IFN-γ to IL-13 (p = 0.006), the difference in the ratios of IL-17A to IL-4 (p = 0.011), and the difference in the ratios of IL-17A to IL-13 (p = 0.029). The biomarkers IFN-γ, IL-13, IFN-γ/IL4, IFN-γ/IL13, IL-17A/IL-4, and IL-17A/IL-13 are representative of the effectiveness of psoriasis treatment. [ABSTRACT FROM AUTHOR]

Congestion is the main therapeutic target of acute heart failure (HF) treatment, and loop diuretics (LDs) are widely used drugs for this purpose. Despite their extensive use, these agents remain largely understudied in terms of modality administration, treatment duration, and escalation dose for subjects responding poorly to therapy. LDs were initially investigated in several edematous statuses such as cirrhosis, nephrotic syndrome, and congestive HF and initially approved for the treatment of cardiogenic congestion in 1966. Despite the long history and the undoubted role in congestion management, the use of LDs in the acute phase is mostly based on the physician's experience, the oral amount chronically administered, and clinical decongestion response. Recent literature suggests monitoring diuretic activity by the evaluation of daily diuresis, weight loss, and sample urinary sodium assessment after early intravenous LD administration. More recently, the measurement of urinary sodium integrated with urinary and blood creatinine values and fluid status has been suggested as optimal marker to predict whole diuretic efficiency and to target the optimal dose. However, this method is not easily available in the chronic setting or in patients with recurrent hospitalization taking a high loop diuretic amount. Since high loop diuretic dose is related to diuretic resistance (DR) and poorer outcome, additional diuretics acting in different nephron sites are often required. Current sequential nephron blockade can stimulate diuresis by synergic mechanisms. This strategy is attempted in patients with poor response, revealing good results in the early period, but the effects of neuro-endocrine stimulation and electrolyte balance across long-term follow-up are still questioned. This paper reviews the historical course of loop diuretics and highlights the need for a universal approach based on clinical conditions, cardio–renal interactions, and HF phenotypes. [ABSTRACT FROM AUTHOR]