Background: Acute cellular rejection (ACR) after heart transplantation remains incompletely explained despite standardized immunosuppression. Environmental exposures may contribute to residual immune activation; however, prior studies have focused primarily on air pollution rather than residential land-use composition. Objectives: To determine whether buffer-specific residential environmental composition is associated with rejection risk and whether these associations are scale-dependent and domain-specific. Methods: In this retrospective single-center cohort study, 30 heart transplant recipients contributed 267 biopsy-linked observations. Residential land-use composition was quantified within 300 m, 500 m, 700 m, and 1000 m buffers and aggregated into five domains: trees, other green surroundings, roads, water, and industrial land. Associations with ACR were evaluated using clustered logistic regression models adjusted for time since transplantation. Results: The strongest and only statistically robust associations after FDR correction were observed within the 300 m buffer. Tree-dominant (OR 1.42, 95% CI 1.22-1.65, q = 0.010) and industrial land exposure (OR 1.50, 95% CI 1.28-1.76, q = 0.010) were independently associated with increased odds of ACR. At 500 m, the association with trees persisted nominally (OR 1.39, 95% CI 1.03-1.88, p = 0.034), but did not remain significant after FDR correction, whereas water exposure showed a non-significant trend (OR 1.28, p = 0.057), which did not reach statistical significance. No associations were observed beyond 700 m across all models. Conclusions: Residential environmental composition may be associated with acute cellular rejection after heart transplantation in a scale-dependent manner, with signals confined to the immediate residential environment. Tree-dominant exposure within 300 m showed an association in clustered models; however, this finding was attenuated in mixed-effects sensitivity analyses. These results should be considered exploratory and hypothesis-generating study.
Background: Tourette syndrome (TS) is a chronic neurodevelopmental disorder with a significant rate of patients remaining refractory to standard treatments. Refractory TS is defined as the persistence of clinically significant tics causing functional impairment despite adequate trials of both behavioral therapy and at least two generally accepted pharmacological treatments from different classes, administered at appropriate doses and durations. This systematic review synthesizes the current evidence on alternative pharmacological and non-pharmacological interventions for treatment-resistant TS. Methods: The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. PubMed, Embase, and Scopus were searched for studies published from 2010 onward. Eligible publications included randomized and non-randomized clinical studies, and case reports evaluating alternative interventions in refractory TS, excluding deep brain stimulation. The primary outcome measures included validated scales assessing tic severity and functional impairment, with available data demonstrating reductions in tic severity, including clinically meaningful improvements reported in several studies. Thirteen studies met the inclusion criteria, comprising five clinical studies (including three randomized trials) and eight case reports. Heterogeneity across studies was primarily driven by differences in study design, patient populations, and variability in intervention types, protocols, and outcome assessments. Results: Investigated interventions included cannabinoids, valproic acid, deep transcranial magnetic stimulation, neurofeedback, biofeedback, electroconvulsive therapy, and ablative neurosurgical procedures. Cannabinoid-based treatments showed potential reductions in tic severity; however, results were inconsistent and often not statistically significant, with evidence largely derived from small or uncontrolled studies. Evidence for non-pharmacological approaches was limited and largely derived from individual cases, with some modalities showing potential benefit in specific subgroups, such as patients with comorbid obsessive-compulsive disorder. Conclusions: Overall, alternative interventions may offer therapeutic value for selected individuals with treatment-resistant TS, with the greatest data regarding cannabinoid use; however, the current evidence base remains heterogeneous and methodologically constrained. Deep transcranial magnetic stimulation might be beneficial in a specific patient population. Larger, well-controlled studies are required to clarify efficacy, safety, and treatment response.
Supraclavicular nerves (SCNs) emerge from the cervical plexus and provide sensation to the skin over and below the clavicle. Detailed knowledge of their course and variation is especially useful in surgeries of the clavicular and neck regions. Anatomical descriptions of the SCNs remain inconsistent across studies. This systematic review aims to provide a comprehensive, evidence-based analysis of SCN anatomy, including its course, branching pattern, and surgical relevance. A systematic search was conducted across major electronic databases (PubMed, Scopus, Embase, ScienceDirect, and Web of Science) to identify original studies reporting morphometric and branching data on SCNs. Studies that were review articles, case reports, letters to the editor, conference abstracts, or performed on animals were excluded. The methodological quality of the included studies was assessed using the Anatomical Quality Assurance (AQUA) Tool developed by the Evidence-Based Anatomy Working Group. This review was registered in the PROSPERO database, ID CRD420251005988. A total of 5 studies, encompassing 175 dissected nerves, were included in this part of the review. Most studies originated in Europe. Supraclavicular nerves are purely sensory and arise from the cervical plexus, providing sensation to the skin over the shoulder, clavicle, sternoclavicular joint, and acromioclavicular joint. They emerge as a single trunk in 95% of cases, wrapping around the sternocleidomastoid muscle before branching over or within the posterior cervical triangle into medial, intermediate, and lateral SCNs. Supraclavicular nerves cross the clavicle in a predictable pattern, with variations in location and division relevant to clinical and surgical applications. This review synthesizes data on SCN anatomy. Precise anatomical knowledge of the SCNs is essential to minimize iatrogenic injuries during neck and clavicle surgeries. However, due to variability in study methodologies and reporting quality, further high-quality anatomical studies are needed to refine surgical guidelines and enhance clinical applications.
Background: Dyspnea is a common reason for emergency medical service (EMS) interventions and is associated with a substantial risk of severe clinical course, complications, and hospital admission. Its differential diagnosis in the prehospital setting remains challenging due to the limited availability of imaging modalities. Point-of-care ultrasound (POCUS), including lung ultrasound (LUS), is a rapid, field-applicable technique recommended in numerous acute respiratory diagnostic scenarios. Objective: To evaluate the use of lung ultrasound in the prehospital setting and its association with the precision of diagnoses related to respiratory failure, the frequency of transport to the emergency department (ED) among patients presenting with dyspnea/respiratory failure, and to characterize the profile of sonographic findings with their correlation to clinical diagnostic categories. Additionally, transport rates in the study population were compared with aggregated regional data for the Masovian Voivodeship (excluding the analyzed county). Methods: A retrospective observational study was conducted on EMS interventions performed between 01 January 2025 and 30 June 2025 in Legionowo County (N = 353). The analysis included ICD-10 codes assigned in prehospital documentation (one primary code and up to two additional codes) in patients presenting with dyspnea and/or respiratory failure, the performance of ultrasound examination, and resulting LUS findings (absence of pleural sliding and/or lung point; B-lines; consolidations; C-lines; pleural effusion). Descriptive analyses, frequency comparison tests (χ2/Fisher), estimation of relative risk (RR) with 95% confidence intervals (CI), and agreement analysis using Cohen's kappa coefficient (κ) between etiological categories derived from ICD-10 codes and those inferred from LUS profiles were performed (κ with 95% CI estimated using bootstrap resampling). The study was reported in accordance with the STROBE guidelines for observational studies. Additionally, the distribution of ICD-10 coding and the proportion of hospital transports across the entire Masovian Voivodeship were compared with those observed in the analyzed area. Results: Ultrasound examination was performed in 72/353 (20.4%) EMS interventions; transport to the emergency department occurred in 239/353 (67.7%) cases. The most frequent clinical categories based on ICD-10 codes were: general/symptom-based 182/353 (51.6%), inflammatory 77/353 (21.8%), obstructive 66/353 (18.7%), and cardiological 20/353 (5.7%). Among abnormal LUS findings, the most common were B-lines (43/72; 61.4%) and consolidations (29/72; 41.4%). Consolidations were strongly associated with the inflammatory category (OR 9.72; p < 0.001), whereas B-lines were associated with the cardiological category (OR 23.41; p = 0.0011) among cases in which LUS was performed. Ultrasound use was associated with a higher frequency of assigning at least one targeted (non-symptom-based) diagnosis within ICD coding: 53/72 (73.6%) vs. 111/278 (39.9%), RR 1.84 (95% CI 1.51-2.25; p < 0.001). Agreement between the ICD-10 etiological category (inflammatory/cardiological/obstructive/other) and the category inferred from the LUS profile was moderate: κ = 0.36 (95% CI 0.21-0.51), with an observed agreement of 54.2%. Compared with aggregated regional data (Masovian Voivodeship excluding the analyzed county), the overall transport rate for comparable ICD-10 codes was lower in the study unit: 279/409 (68.2%) vs. 11,351/13,785 (82.3%), RR 0.83 (95% CI 0.78-0.89; p < 0.001). The largest differences were observed for dyspnea (R06.0: 72.9% vs. 88.2%; RR 0.83) and obstructive codes (J44/J45/J46 combined: 43.1% vs. 67.0%; RR 0.64). Conclusions: In this retrospective analysis, an EMS unit with systematically implemented ultrasound demonstrated a lower frequency of hospital transport for selected dyspnea/respiratory failure codes compared with regional data and greater precision in ICD-10 diagnostic coding in cases where ultrasound was performed. The profile of LUS findings correlated with clinical categories in a manner consistent with existing literature.
Liberica coffee (Coffea liberica), including its varieties C. liberica var. liberica and C. liberica var. dewevrei (Excelsa), is the third most commercially important coffee species; however, scientific knowledge on its physicochemical, bioactive, and sensory characteristics remains limited compared with Arabica and Robusta. This study evaluates the development of Liberica coffee research and synthesizes current evidence on its key quality attributes. A bibliometric analysis of publications indexed in Scopus, PubMed, and Semantic Scholar was conducted to identify trends, themes, and knowledge gaps, followed by a targeted review of physical properties, bioactive compounds, antioxidant and antibacterial activities, and sensory characteristics. Results show a gradual increase in Liberica research over the past decade, with a shift toward quality attributes and functional properties. Liberica coffee exhibits distinctive physical traits, moderate caffeine levels, and a bioactive profile characterized by chlorogenic acids that vary with processing and roasting, alongside relatively stable alkaloids such as trigonelline and theobromine. The diterpene composition, particularly the kahweol-to-cafestol ratio, distinguishes Liberica varieties. Sensory studies report fruity, jackfruit-like aromas, moderate acidity, and a relatively full body. Despite its potential, standardized data remain limited, highlighting the need for integrated research to support quality differentiation and value addition.
Wildlife-vehicle collisions (WVCs) are a global biodiversity threat impacting most terrestrial vertebrates and posing scientific, economic and conservation challenges. Research on WVC is nevertheless geographically uneven, and large-scale multi-taxon studies are scarce. We analysed data from the Polish Roadkill Observation System, a nationwide volunteer-based programme recording WVC carcasses across all terrestrial vertebrates. Based on 28,709 casualties recorded during 2000-2022, we examined the mortality patterns in vertebrate classes and some correlates of WVCs distribution. In total, 205 species were identified, representing 55% of Poland's terrestrial vertebrate fauna, including 16% of threatened species. The approximate proportion of roadkilled mammals, amphibians, birds and reptiles was 8:8:5:1; mammals and amphibians are thus the most frequently reported vertebrates on Polish roads by citizen scientists. Reports of multiple casualties concerned mostly amphibians and reptiles, and were often associated with protected areas. Regression models revealed that observed roadkill was positively correlated with body mass and carcass persistence but not with species distribution range in Poland. Prominent seasonal patterns were also evident, with peak mortality occurring in warm seasons and coinciding with taxon-specific phenological events. Our study demonstrates the value of citizen-science data for identifying nationwide patterns of WVCs, while also highlighting the need to move beyond opportunistic observations toward a nationally coordinated, systematic survey to generate more accurate and policy-relevant estimates.
Background/Objectives: The loss of orthodontic microimplants is a common clinical complication that significantly disrupts the continuity of malocclusion treatment. Despite increasing clinical use of microimplant reinsertion, the factors influencing its success remain unclear. The aim of this exploratory systematic review was to examine the available literature regarding clinical outcomes related to the retention of orthodontic microimplants following their reinsertion. Methods: Studies that assessed the success of orthodontic microimplant reinserted were included in the review. Searches were conducted on 27 September 2025, in the following databases: BASE (Bielefeld Academic Search Engine), PubMed, Scopus, and EMBASE. The ROBINS-I (Risk of Bias in Non-randomized Studies-of Interventions) tool was used to assess the risk of bias. Due to heterogeneity of included studies, a narrative synthesis was performed. Results: Four of the 577 studies were included in the review. A total of 305 microimplants were reinserted in 276 patients. The overall success rate ranged from 44.16% to 66%. Analysis indicated a significantly higher success rate in the maxilla (up to 68.60%) compared to the mandible (lowest 36.84%). Furthermore, a narrative synthesis suggests better clinical outcomes for 8 mm long microimplants compared to 6 mm ones, as well as reduced reinsertion success in areas with high cancellous bone density. Regarding the modification of the insertion site, the current data are contradictory; while some studies indicate significant benefits from changing the site (e.g., to the midpalatal suture), others show no statistical difference compared to reinsertion at the same site. Overall, the evidence remains limited and heterogeneous. Conclusions: The current review of the literature on the success of reinsertion of orthodontic microimplants is subject to a high risk of misinterpretation, due to the limited amount of data and the risk of unidentified confounding factors. Further standardized clinical trials are needed to develop unified protocols for these procedures. Other: The review was prospectively registered with the Open Science Framework (OSF); osf.io/tbj2s.
BackgroundWomen with atrial fibrillation (AF) have historically been considered to have higher thromboembolic risk than men. The CHA2DS2-VASc score treated female sex as an independent risk factor. Recent guidelines recommend CHA2DS2-VA score, redefining female sex as a risk modifier.AimsThis study aimed to assess the prevalence of left atrial appendage thrombus (LAAT) by sex and identify independent predictive factors for LAAT.MethodsThis analysis used data from the multicenter, prospective Left Atrial Thrombus on Transesophageal Echocardiography (LATTEE) registry, including 3,109 patients with AF. All patients underwent preprocedural transesophageal echocardiography to assess LAAT.ResultsWomen constituted 36.5% of the study population. They were older, had more comorbidities, higher CHA2DS2-VA scores compared with men (median 3 vs. 2, p < 0.001). Among 3034 patients, LAAT was detected in 7.7% of cases, without significant difference between sexes (8% vs. 7.2%, p = 0.42). In multivariable logistic regression, paroxysmal AF was associated with lower odds of LAAT (OR 0.35), smoking (OR 1.71), reduced left ventricular ejection fraction (LVEF) <50% (OR 1.94), DOAC use (OR 0.42), and LAAV (per 1 cm/s increase; OR 0.92) were independent predictors of LAAT in men. In women only LAAV (per 1 cm/s increase; OR 0.91) remained significant (p < 0.001). No sex-related effect modification was observed (p > 0.05).ConclusionsAlthough women with AF present a more adverse clinical profile, sex itself was not an independent predictor of LAAT.
The use of resin-based composite imitating gum tissue enhances the aesthetics of fillings located below the physiological gum line. The shear bond strength (SBS) between the gum-imitating composite and the traditional composite with different surface preparation methods was examined. The aim of the study was to evaluate which base material-G-aenial Universal Injectable (GC, Japan, flow) or G-aenial A'CHORD (GC, Japan, paste)-performs better, as well as to determine the most effective preparation method among sandpaper (control), 36% orthophosphoric acid (H3PO4), sandblasting, and 9.5% hydrofluoric acid (HF). The tested gum-imitating material was Amaris Gingiva (VOCO, Germany). The connection between the composites was evaluated using a Z005 (Zwick-Roell) universal device. Surface tests were carried out using an SJ-410 (Mitutoyo) profilometer. Evaluation of the prepared surface structures was performed using scanning electron microscopy (HITACHI S-4700). Etching with HF significantly improved the shear bond strength between composites. Sandblasting also enhanced the adhesion results, but the H3PO4 group achieved comparable results to the control group. However, since HF is not recommended for intraoral use, sandblasting (30 μm aluminum oxide particles applied with three passes at constant speed under a pressure of 2 bar from 1.5 cm) appears to be the most suitable clinical alternative.
Sparassis crispa (cauliflower mushroom) is an edible medicinal fungus known for its diverse array of bioactive metabolites. Despite its established nutritional and pharmacological relevance, its antimicrobial, antiviral, and antiparasitic activities remain insufficiently investigated. In the present study, extracts of the fruiting bodies of S. crispa were prepared using four solvents (water, 60% ethanol, methanol-acetone-water [3:1:1], and 1% acetic acid) and evaluated for their chemical composition and broad-spectrum biological activities. UHPLC-MS/MS profiling revealed distinct metabolite profiles among the extracts, including identification of nucleosides such as adenosine and methylthioadenosine. All extracts exhibited nematicidal activity against Rhabditis sp. nematodes in a dose-dependent manner, with the 60% ethanol extract being the most potent (LD50 = 4.2 mg/mL). In antiviral assays, the water extract partially inhibited Coxsackievirus B3 (CVB3) replication, reducing infectious titers by approximately 2 log units, whereas none of the extracts showed a significant effect against Herpes simplex virus type 1 (HSV-1). Antibacterial testing demonstrated activity only for the 1% acetic acid extract, which inhibited several Gram-positive and Gram-negative bacteria at minimum inhibitory concentrations of 10-20 mg/mL. No antifungal activity against Candida spp. was observed. These findings identify Sparassis crispa as a promising edible source of bioactive compounds, exhibiting pronounced nematicidal and moderate antimicrobial activities, and support its potential application in the development of functional foods and nutraceuticals. They further justify targeted isolation and mechanistic studies to characterize the metabolites responsible for these effects and to clarify their relevance for food-based health promotion.
This article concerns the issue of contactless estimation of the complex electrical permittivity of masonry materials by means of a microwave technique in the frequency domain. The main aim of the study was to develop a method enabling the determination of the real part of relative permittivity and the electrical conductivity of ceramic building materials using microwave reflection measurements, as well as to assess the applicability of the proposed approach for moisture diagnostics in porous media. The research was performed using a reflection-mode measuring setup comprising a vector network analyser and a broadband horn antenna, while measurements were carried out in the frequency range from 1 to 6 GHz on samples of solid ceramic brick with six gravimetric moisture levels. A one-dimensional model of electromagnetic wave propagation in the material was developed, considering complex permittivity, impedance transformation, and a calibration procedure compensating for the influence of the antenna and free-space propagation. Based on the fitting of the magnitude and phase characteristics of the reflection coefficient, the electrical parameters of the tested samples were estimated. The results obtained showed an increase in both permittivity and conductivity with increasing moisture content and revealed very good agreement with the reference values determined using the time-domain method. It can be concluded that the frequency-domain microwave approach may be effectively applied for contactless and non-destructive diagnostics and estimation of the dielectric properties and moisture content in ceramic materials.
Lightweight structures such as Schwedler domes offer high strength-to-weight ratios for large-span applications; however, their design typically involves time-consuming iterative processes. This study proposes an integrated parametric workflow combining geometry generation, structural analysis, and automated load application to improve both design efficiency and structural performance. The methodology is based on Python scripting within Grasshopper, enabling parametric control of dome geometry and direct interoperability with Autodesk Robot Structural Analysis Professional. Three open-apex Schwedler dome configurations were analyzed as a focused demonstration of the workflow, differing in cross-sectional typology and structural layout. The results show that the use of closed sections reduces structural mass by up to 31%, while hybrid configurations achieve significantly improved member utilization, reaching 0.87 for ribs and 0.63 for rings. Importantly, the parametric workflow enabled the rapid generation and evaluation of multiple design variants, significantly reducing modeling time and eliminating inconsistencies between geometric and analytical models. The study demonstrates that parametric modeling provides an effective framework for designing efficient dome structures, enabling both material optimization and accelerated design processes. The same parametric source is also suitable for extension into BIM and fabrication environments, as well as into life-cycle assessment, which are identified as planned continuations of this research.
Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism caused by ATP7B mutations, characterized by hepatic copper accumulation and multisystem involvement. Several rare inherited and acquired conditions can closely mimic WD, posing diagnostic challenges and the risk of inappropriate therapy. By examining neuroimaging patterns and distinguishing between diagnostic criteria, this narrative review provides a comprehensive synthesis of WD-mimicking disorders, emphasizing their molecular mechanisms, clinical phenotypes, and biochemical features. WD-mimicking disorders encompass ATP7A-related neurodegenerations (Menkes disease, occipital horn syndrome, X-linked distal hereditary motor neuropathy), MEDNIK syndrome, Huppke-Brendel syndrome, aceruloplasminemia, congenital disorders of glycosylation, primary familial intrahepatic cholestasis type 3, and acquired copper deficiency syndromes. Mechanisms include systemic copper deficiency, impaired intracellular trafficking, defective ceruloplasmin biosynthesis, secondary hepatic copper accumulation, and abnormal glycosylation. Clinical features range from neurodevelopmental delay, movement disorders, and hepatic dysfunction to dermatologic, hematologic, and connective-tissue abnormalities. Biochemical profiles may overlap with WD, particularly low serum ceruloplasmin and total copper, altered urinary copper excretion, and elevated hepatic copper in some disorders. Neuroimaging and genetic testing provide critical discriminative value. Management is largely supportive, with disease-specific therapies available in selected conditions, such as subcutaneous copper in Menkes disease or monosaccharide supplementation in certain congenital disorders of glycosylation subtypes. Accurate differentiation between WD and WD-mimicking disorders requires careful integration of clinical, biochemical, imaging, and molecular data. Recognition of distinctive features and understanding underlying pathophysiology are essential to avoid misdiagnosis and inappropriate anti-copper therapy, optimize management, and improve patient outcomes.
Accurate exclusion of cribriform growth (GP4Crib+), an adverse histologic feature in prostate cancer, remains a challenge in selecting intermediate-risk patients for active surveillance (AS). This study evaluates whether an MRI-based radiomics model predicting GP4Crib+ can support AS inclusion decisions under the assumption that intermediate-risk men without GP4Crib+ could be safely managed with AS. This single-center retrospective study was approved by the institutional review board (IRBd21-108) and included men with Cambridge Prognostic Group (CPG) -1, CPG-2, or CPG-3 (Gleason grade (GG) 2) prostate cancer who underwent MRI and radical prostatectomy. In this cohort, a previously trained radiomics model was applied across the whole prostate to generate voxel-wise GP4Crib+ probability maps, to ultimately identify men with GP4Crib. This model was tested in two scenarios: (1) CPG-1+2, and (2) CPG-1+2+3(GG2) patients on biopsy. The reference scenario was CPG-1 men to AS (guideline recommendations). We included 127 patients (median age 66 years, interquartile range 47‒78). Standalone radiomics performance was moderate (area under the receiver operating characteristic curve (AUROC): 0.68 overall; 0.60 for CPG-2; and 0.70 for CPG-3(GG2)). At a 0.60 probability threshold, the model reduced overtreatment by 9% in CPG-1 + 2 men (with 1% increase in undertreatment). In CPG-1+2+3(GG2) men, the model reduced overtreatment by 8%, maintaining low undertreatment (3%). Most false negatives involved smaller than 1.5-mm cribriform foci. Our MRI-based GP4Crib+ radiomics model is able to support AS decisions in men with CPG-1+2+3(GG2). Despite modest standalone diagnostic performance, its integration into the clinical work-up may help safely expand AS selection to intermediate-risk men, ultimately reducing overtreatment. MRI-based radiomics may support noninvasive exclusion of cribriform growth to guide active surveillance eligibility in intermediate-risk prostate cancer, enabling safer management decisions and reducing unnecessary treatment. Prostate cancer cribriform growth is difficult to detect but crucial for treatment decisions. MRI radiomics helps exclude cribriform growth in intermediate-risk prostate cancer patients. Radiomics-informed decisions reduced overtreatment under structured AS scenarios.
Atypical Parkinsonisms are a diverse group of diseases associated with multiple pathologies, including synucleinopathies and tauopathies. Atypical Parkinsonisms include progressive supranuclear palsy, corticobasal degeneration, multiple system atrophy, and dementia with Lewy bodies. The examination of these diseases is complicated due to their overlapping clinical manifestations. Hence, tools enabling reliable supplementary assessment of atypical Parkinsonisms are needed. The most common methods involve neuroimaging; however, these evaluations generally involve basic magnetic resonance imaging and indicate possible morphological changes. Less attention is given to disease background assessment. Biochemical assessment enables a more detailed examination of the factors impacting neurodegenerative processes. The features that may impact the pathophysiology of these diseases include metabolic abnormalities, excessive inflammation, and environmental factors. In this context, proteomic evaluation, as analyzed in this article, could partly address the insufficiently described aspects of the unclear pathological mechanisms related to atypical Parkinsonisms.
We showed recently that the adenosine system and nitric oxide (NO) can interact differently in the control of renal function in normoglycaemia (NG) versus streptozotocin-induced diabetes (DM). Herein, we investigated if this relationship is modulated by dietary betaine (Bet, food compound possessing antioxidant and anti-inflammatory properties), to examine if adenosine receptor signalling in NG and DM females is altered by chronic Bet supplementation. The effects of intravenous infusion of theophylline, non-selective adenosine receptor antagonist, were examined in anaesthetised Sprague-Dawley female rats, pretreated for 2 weeks with Bet alone or combined with 4-day NO synthesis blockade with L-NAME (Bet + L-NAME). Renal blood flow (RBF, ultrasound artery probe), perfusion of the cortex, outer (OM-BF) and inner medulla (IM-BF; laser-Doppler technique), and tissue NO signal (selective electrode) were determined along with renal excretion. Bet and Bet + L-NAME decreased baseline RBF irrespective of glycaemia, whereas Bet lowered (NG) or elevated (DM) basal OM-BF; Bet + L-NAME treatment abolished these effects. Baseline sodium excretion decreased after Bet and Bet + L-NAME in NG only. Bet modified theophylline effects: IM-BF was lowered in DM rats, while tissue NO changes shown in the control were modified: NO increased in NG and decreased in DM. In NG, these effects were abolished by Bet + L-NAME. Bet pretreatment did not alter diuresis, natriuresis and kaliuresis, but after Bet + L-NAME these parameters increased (NG) or decreased (DM). Dietary Bet has the potential to affect renal medullary blood circulation; however, the eventual effect depends on glycaemia. Bet can modify renal functional changes induced by the interplay of the adenosine and NO systems, both in rats with normoglycaemia and streptozotocin diabetes.
Functionally single-ventricle (FSV) defects are complex congenital heart anomalies that require Fontan palliation, a surgical procedure redirecting systemic venous blood directly to the pulmonary arteries, bypassing the heart. Despite improvements in surgical techniques and perioperative care leading to enhanced survival rates, patients remain vulnerable to significant long-term complications, due to the unique Fontan circulation physiology. This circulation relies on low pulmonary vascular resistance and preserved single-ventricle function but predisposes patients to venous congestion and reduced cardiac output, resulting in multi-organ dysfunction. Key cardiovascular complications include systolic and diastolic dysfunction of the single ventricle, atrioventricular valve regurgitation, arrhythmias, pulmonary vascular disease, and thromboembolic events. Systemic complications encompass Fontan-associated liver disease (FALD), protein-losing enteropathy (PLE), plastic bronchitis (PB), renal impairment, and endocrine and psychosocial burdens. All the problems induce frequent hospitalizations, psychological challenges, and impaired educational and employment opportunities. Comprehensive management requires multidisciplinary approaches addressing the complex interplay of hemodynamic, organ-specific problems, and psychosocial factors inherent to Fontan physiology.
Arterial hypertension might lead to serious organ damage and complications like hypertensive retinopathy. The retina is the only place in the human body where microscopic blood vessels can be directly investigated. This enables early diagnosis of arterial hypertension-mediated organ damage. Untreated hypertensive retinopathy leads to vision loss in its advanced stages. There are many methods of assessing changes in the arterioles; however, the most accurate is adaptive optics (RTX1™ device with AODetectArtery software, ver. 3.0., Imagine Eyes, Orsay, France). It provides a resolution of 1.6 μm, which is superior to conventional imaging techniques. Optical coherence tomography angiography can serve as an early, minimally invasive marker of microvascular damage. Across the studies analyzed, the WLR (Wall-to-Lumen Ratio) exhibited significantly higher values when comparing individuals with hypertensive retinopathy to normotensives (0.31 vs. 0.26). The main aim of this review is to present the application of adaptive optics in the early diagnosis of hypertensive retinopathy. The search strategy included 267 original studies, among which 12 were selected to be described and analyzed in this review based on criteria including original research and studies performed on humans with hypertensive retinopathy. RTX1™ enables the assessment of arterial parameters such as the Wall Thickness (WT), Lumen Diameter (LD), Outer Diameter (OD), Wall-to-Lumen Ratio (WLR) and Wall Cross Sectional Area (WCSA). These parameters differ depending on the arterial hypertension. The WLR was identified to be the parameter that differs in the vast majority of analyzed studies when comparing hypertensive patients to normotensive patients. Vascular parameters were also found to change depending on different organisms' states, treatment applications and etiological causes of disease. Furthermore, changes in retinal arterial parameters were associated with increased cardiovascular risk in observational studies. RTX1™ was also identified to provide very good intra- and interobserver variability. RTX1™ is a valuable tool in the examination of arterial vessels and in establishing associations between retinal vascular parameters and a patient's clinical state.
An Endocrine Society Clinical Practice Guideline on vitamin D was published in 2024. Its main objective was the use of vitamin D to lower the risk of disease in individuals without established indications for vitamin D treatment or 25-hydroxavitamin D (25(OH)D) testing. The methodology followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) and the Evidence-to-Decision (EtD) framework. Evidence from randomized controlled trials (RCTs) retrieved by a systematic review was prioritized to inform this guideline. It was concluded that vitamin D supplementation reduces rickets and respiratory tract infections in children, mortality in individuals aged 75 years or older, pregnancy complications (outcomes), and progression of prediabetes to diabetes mellitus. Consequently, empiric vitamin D supplementation was recommended for individuals aged 1 to 18 years and ≥75 years, pregnant women, and individuals with prediabetes. Empiric vitamin D supplementation is defined as a vitamin D intake that exceeds the Dietary Reference Intakes (DRIs) and is implemented without 25(OH)D testing. This article provides a comprehensive guideline summary and critical appraisal based on a narrative review on scientific publications regarding that guideline. Several publications discussed the 2024 Endocrine Society Clinical Practice Guideline on vitamin D. The main criticisms and discussion relate to unclear vitamin D dosages, guideline applicability to certain populations including controversy with previous vitamin D guidelines, and the implications of 25(OH)D testing. The 2024 Endocrine Society Clinical Practice Guideline on vitamin D followed a rigorous methodological approach with high quality standards but it leaves many open questions and uncertainties warranting clarification.
Plant-derived sweet proteins are promising low-calorie natural sweeteners that may reduce dietary sugar intake and prevent non-communicable diseases. Although seven have been identified-thaumatin, miraculin, monellin, mabinlin, brazzein, pentadin, and curculin (neoculin)-only thaumatin is currently approved as a food additive. The development of others requires comprehensive safety assessments, particularly regarding allergenicity. This systematic review aims to investigate and synthesize allergenicity assessment methods (in silico, in vitro, in vivo, and clinical) applied to these seven sweet proteins. The literature searches were conducted following PRISMA guidelines across Scopus, PubMed, and Wiley Online Library databases, up to 30 November 2025, with no time restrictions. The risk of bias in selected studies was evaluated using GRADE. After the selection process, 14 out of 2634 studies met the inclusion criteria. Thaumatin, miraculin, monellin, and brazzein emerged as the most extensively studied proteins. In silico approaches (sequence and structural homology) and in vitro assays (digestibility and cell-based methods) were the most commonly employed methods. In contrast, in vivo studies (animal models) and clinical evaluations (skin prick tests, oral food challenges) were rarely reported. Allergenicity studies on pentadin, mabinlin, and curculin (neoculin) are limited, indicating a research gap that requires further study to support regulatory approval and consumer acceptance.