Search Results (1,024)

Background: Cardiac involvement is common in Fabry disease (FD) and typically manifests with left ventricular hypertrophy (LVH). Patients with FD are frequently misdiagnosed, and this is mainly related to the lack of disease awareness among clinicians. The aim of this study was to determine whether providing a targeted educational intervention on FD may enhance FD diagnosis. Methods. This research was designed as a single-arm before-and-after intervention study and evaluated the impact of providing a specific training on FD to cardiologists from different Italian centers, without experience in rare diseases. In the 12-month period after the educational intervention, the rate of FD screening and diagnosis was assessed and compared with those conducted in the two years preceding the study initiation. Results: Fifteen cardiologists participated to this study, receiving a theoretical and practical training on FD. In the two previous two years, they conducted 12 FD screening (6/year), and they did not detect any cases of FD. After the training, they performed 45 FD screenings, with an eight-fold rise in the annual screening rate. The screened population (age: 61 ± 11 years, men: 82%) was mainly composed of patients with unexplained LVH (n = 43). There were four new FD diagnoses and, among of them, three had a late-onset GLA variant. After the cascade genetic screening, 11 affected relatives and 8 heterozygous carriers were also detected. Conclusions: A targeted educational intervention for cardiologists allowed the identification of four new families with FD. Enhancing FD awareness is helpful to reduce the diagnostic and therapeutic delay. Full article

Mountains are global biodiversity hotspots but face the danger of habitat loss, especially at lower elevations due to climate-warming-induced forest dieback. In the Gongga Mountains (SW China), Abies fabri trees at 2800 m show increased mortality, yet the causes remain unclear. We assessed climatic influences and bark beetle infestations on tree vigor and radial growth, comparing healthy and declining trees at 2800, 3000, and 3600 m elevations. Leaf nitrogen and phosphorus concentrations were measured to evaluate nutrient status. From 1950 to 2019, mean annual temperatures rose at all elevations, while precipitation decreased at low elevations, negatively correlating with temperature. Such warmer, drier conditions impaired low-elevation trees. The decline in A. fabri growth began in the late 1990s to early 2000s, with an earlier and more pronounced onset at lower elevations. A clear lag is evident, as trees at 3000 m and 3600 m showed either delayed or minimal decline during the same period. High-elevation trees experienced more stable climate and better nutrient availability, supporting greater growth and leaf nitrogen in healthy trees. Bark beetle infestations were worst in declining trees at the highest elevation. Our results reveal that A. fabri vigor shifts along elevation gradients reflect interactions between abiotic and biotic stressors, especially aridification. Full article

Background: The longitudinal RisCoin study investigated risk factors for COVID-19 vaccination failure among healthcare workers (HCWs) and patients with inflammatory bowel disease (IBD) at a University Hospital in Germany. Since the hospital served as the study sponsor and employer of the HCW, we implemented a custom mobile application. We aimed to evaluate the implementation, adherence, benefits, and limitations of this study’s app. Methods: The app allowed secure data collection through questionnaires, disseminated serological results, and managed bidirectional communication. Access was double-pseudonymized and irreversibly anonymized six months after enrollment. Download frequency, login events, and questionnaire submissions between October 2021 and December 2022 were analyzed. Multivariable logistic regression identified factors associated with app adherence. Results: Of the 3979 participants with app access, 3622 (91%) used the app; out of these, 1016 (28%) were “adherent users” (≥12 submitted questionnaires). App adherence significantly increased with age. Among HCW, adherent users were more likely to be non-smokers (p < 0.001), working as administrators or nursing staff vs. physicians (p < 0.001), vaccinated against influenza (p < 0.001), and had not travelled abroad in the past year (p < 0.001). IBD patients exposed to SARS-CoV-2 (p = 0.0133) and those with adverse events following the second COVID-19 vaccination (p = 0.0171) were more likely adherent app users. Despite technical issues causing dropout or non-adherence, the app served as a secure solution for cohort management and longitudinal data collection. Discussion: App-based cohort management enabled continuous data acquisition and individualized care while providing flexibility and anonymity for the study team and participants. App usability, technical issues, and cohort characteristics need to be thoroughly considered prior to implementation to optimize usage and adherence in clinical research. Full article

In this work, we present a high-performance tapered quantum cascade laser (QCL) designed to achieve both high output power and low divergence angle. By integrating a tapered waveguide with a Fabry–Perot structure, significant improvements of tapered QCL devices in both output power and beam quality are demonstrated. The optimized 50 µm wide tapered QCL achieved a maximum output power of 2.76 W in pulsed operation with a slope efficiency of 3.52 W/A and a wall-plug efficiency (WPE) of 16.2%, while reducing the divergence angle to 13.01°. The device maintained a maximum power of 1.34 W with a WPE exceeding 8.2%, measured under room temperature and continuous wave (CW) operation. Compared to non-tapered Fabry–Perot QCLs, the tapered devices exhibited a nearly 10-fold increase in output power and over 200% improvement in WPE. This work provides a promising pathway for advancing mid-infrared laser technology, particularly for applications requiring high power, low divergence, and temperature stability. Full article

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by mutations in the GLA gene, resulting in a deficient activity of the enzyme α-galactosidase A (α-Gal A). This deficiency leads to the progressive accumulation of globotriaosylceramide (Gb3) and its deacylated form, globotriaosylsphingosine (Lyso-Gb3), in various tissues, contributing to a broad spectrum of clinical manifestations. Recent evidence highlights the crucial role of inflammation in the pathophysiology of FD, influencing disease progression and clinical outcomes. This review provides a comprehensive overview of the relationship between inflammation and FD, with a particular focus on the impact of inflammatory processes on disease progression and complications. Full article

Objectives: This systematic literature review aimed to identify studies assessing the clinical efficacy and real-world effectiveness of current and emerging treatments for Fabry disease. Methods: Searches of the MEDLINE, EMBASE, and Cochrane library databases, as well as relevant congress proceedings, were conducted to identify publications reporting on studies in patients of any age, sex, race, or ethnicity who received any approved or experimental treatment for Fabry disease, published before 17 June 2024. Results: Of 1881 publications screened, 234 reported data on renal, cardiac, cerebrovascular, and disease severity outcomes from 225 studies. The majority of reported studies were observational in nature (n = 150; 67%) and involved only adults (n = 172; 74%). Study designs and patient populations were highly heterogeneous, and cross-study conclusions about the effectiveness of different therapies could not be made. Enzyme replacement therapy (ERT) with agalsidase alfa or agalsidase beta stabilized renal function and cardiac structure in patients with Fabry disease. Early initiation of ERT in childhood or young adulthood was associated with better renal and cardiac outcomes than treatment initiation at a later age. The small number of comparator studies of agalsidase alfa and agalsidase beta suggested similar efficacy. Patients treated with migalastat and pegunigalsidase alfa also maintained stable renal function and cardiac structure. Conclusions: Overall, current treatments slow the progression of renal and cardiac decline in patients with Fabry disease. Large cohort studies with long-term follow-up and baseline stratification based on clinical phenotype are needed to address evidence gaps and provide clinicians with robust data to inform treatment decisions. Full article

Low-finesse Fabry–Perot (F–P) cavities, widely applied in the field of micro-displacement measurement, offer significant advantages in reducing the influence of higher-order reflections and improving the accuracy of measurement systems. Generally, an F–P cavity finesse of 0.5 is required to achieve high-precision micro-displacement measurements. However, in optical design, low-finesse cavities impose strict requirements on reflectivity, and maintaining fine stability during cavity movement is challenging. Achieving ideal orthogonal interference with a finesse of 0.5 thus presents considerable difficulties. This study proposes a novel low-finesse F–P cavity design that employs a high-reflectivity spherical reflector and the end face of a fiber collimator as the reflective surfaces of the cavity. By utilizing beam divergence characteristics and geometric parameters, a structure with a finesse of approximately 0.5 is quantitatively designed, enabling a simplified implementation without the need for angular alignment. Compared with conventional approaches, this method eliminates the need for precise angular alignment of the reflective surfaces, significantly simplifying implementation. The experimental results show that, under fixed receiving field angles and beam radii of the fiber collimators, ideal orthogonal interference can be achieved by selecting the radius of the reflective sphere. Under varying working distances, the average finesse values of the interference spectra measured by Collimators 1 and 2 are 0.496 and 0.502, respectively, both close to the theoretical design value of 0.5, thereby meeting the design requirements. Full article

Background: Anderson–Fabry disease (AFD) is a progressive lysosomal storage disorder characterized by systemic glycosphingolipid accumulation. While cardiac imaging plays a central role in disease monitoring, the relationship between structural myocardial changes and exercise capacity remains incompletely defined. This study aimed to evaluate functional impairment in AFD patients using cardiopulmonary exercise testing (CPET) and to determine whether limitations are primarily cardiac or extracardiac in origin. Methods: Thirty-one patients with genetically confirmed AFD were retrospectively enrolled from two tertiary centers. All underwent baseline clinical assessment, resting transthoracic echocardiography (TTE), spirometry, and symptom-limited CPET using a cycle ergometer and a 10 W/min ramp protocol. Echocardiographic parameters included the LVEF, global longitudinal strain (GLS), E/e′ ratio, TAPSE, and PASP. CPET measurements included the peak VO₂, anaerobic threshold (AT), VE/VCO₂ slope, oxygen pulse (VO₂/HR), and VO₂/watt ratio. Results: The mean age was 48.4 ± 17.6 years, with most patients classified as NYHA I. LVEF was preserved (62.3 ± 8.6%), and diastolic indices were within normal limits (E/e′ 7.1 ± 2.4), but GLS was impaired (11.3 ± 10.5%). CPET showed reduced peak VO₂ (18.6 ± 6.1 mL/kg/min; 71.4% predicted) and early AT (40.8%), with preserved ventilatory efficiency and oxygen pulse. VO₂/watt was mildly reduced, suggesting peripheral limitations despite intact central hemodynamics. Conclusions: Functional impairment is common in AFD patients, even with mild cardiac involvement. CPET reveals early systemic limitations not captured by standard imaging, supporting its role in phenotypic characterization and therapeutic decision-making. Full article

This paper presents a methodology for extracting and simulating arterial pulse waveform signals from Fabry–Perot interferometric measurements, emphasizing a practical approach for noninvasive cardiovascular assessment. A key novelty of this work is the presentation of a complete Python-based processing pipeline, which is made publicly available as open-source code on GitHub (git version 2.39.5). To the authors’ knowledge, no such repository for demodulating these specific interferometric signals to obtain a raw arterial pulse waveform previously existed. The proposed system utilizes accessible Python-based preprocessing steps, including outlier removal, Butterworth high-pass filtering, and min–max normalization, designed for robust signal quality even in settings with common physiological artifacts. Key features such as the rate of change, the Hilbert transform of the rate of change (envelope), and detected extrema guide the signal reconstruction, offering a computationally efficient pathway to reveal its periodic and phase-dependent dynamics. Visual analyses highlight amplitude variations and residual noise sources, primarily attributed to sensor bandwidth limitations and interpolation methods, considerations critical for real-world deployment. Despite these practical challenges, the reconstructed arterial pulse waveform signals provide valuable insights into arterial motion, with the methodology’s performance validated on measurements from three subjects against synchronized ECG recordings. This demonstrates the viability of Fabry–Perot sensors as a potentially cost-effective and readily implementable tool for noninvasive cardiovascular diagnostics. The results underscore the importance of precise yet practical signal processing techniques and pave the way for further improvements in interferometric sensing, bio-signal analysis, and their translation into clinical practice. Full article

In this paper, we present the development of a new semi-distributed interferometer (SDI) biosensor with a Zn, Cu, and Co metal oxide nanopowder coating for the detection of a kidney disease biomarker as a model system. The combination of nanopowder coating with the SDI platform opens up unique opportunities for improving measurement reproducibility while maintaining high sensitivity. The fabrication of sensors is simple, which involves one splice and subsequent cutting at the end of an optical fiber. To ensure specific detection of the biomarker, a monoclonal antibody was immobilized on the surface of the probe. The biosensor has demonstrated an impressive ability to detect biomarkers in a wide range of concentrations, from 1 aM to 100 nM. The theoretical limit of detection was 126 fM, and the attomolar detection level was experimentally achieved. The sensors have achieved a maximum sensitivity of 190 dB/RIU and operate with improved stability and reduced dispersion. Quantitative analysis revealed that the sensor’s response gradually increases with increasing concentration. The signal varies from 0.05 dB at 1 aM to 0.81 dB at 100 nM, and the linear correlation coefficient was R² = 0.96. The sensor showed excellent specificity and reproducibility, maintaining detection accuracy at about 10⁻⁴ RIU. This opens up new horizons for reliable and highly sensitive biomarker detection, which can be useful for early disease diagnosis and monitoring using a cost-effective and reproducible sensor system. Full article

This study proposes a Fabry–Perot interferometric system and an associated evaluation method for measuring the weight of moving trains. An optical fiber sensor, comprising a sensing fiber and a supporting structure, is securely bonded to the rail foot. As a train traverses the track, the resulting localized bending induces a change in the sensing fiber’s length, which manifests as a quantifiable phase shift in the interference signal. We developed a physical–mathematical model, based on three Gaussian functions, to describe the temporal change in sensing fiber length caused by the passage of a single bogie. This model enables the determination of a proportionality constant to accurately convert the measured phase change into train weight. Model validation was performed using a train set, including a locomotive and four variably loaded wagons, traveling at 15.47 km/h. This system offers a novel and effective approach for real-time train weight monitoring. Full article

In this study, a terahertz microfluidic multi-band sensor was designed. Unlike previous microfluidic absorption sensors that rely on dipole resonance, the proposed sensor uses a physical mechanism for absorption by exciting higher-order lattice resonances in microfluidic structures. With a Fabry–Perot cavity, the sensor can form an absorption peak with a high quality factor (Q) and narrow full width at half maximum (FWHM). A high Q value and a narrow FWHM are valuable in the field of sensing and provide strong support for high-precision sensing. On this basis, the sensing performance of the device was investigated. The simulation results clearly show that the absorption sensor has ultra-high sensitivity, which reaches 400 GHz/Refractive Index Unit (RIU). In addition, the sensor generates three absorption peaks, overcoming the limitations of a single frequency band in a composite resonance mode and multidimensional frequency response, which has potential application value in the field of volatile organic compound (VOC) sensing. Full article

Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene, resulting in α-galactosidase A (α-Gal A) deficiency and progressive accumulation of globotriaosylceramide (Gb3). Current therapies, such as enzyme replacement and chaperone therapy, have limitations, including incomplete biodistribution and mutation-specific efficacy. Gene therapy using adeno-associated virus (AAV) vectors presents a promising alternative. Methods: In this study, we assessed the dose-dependent effects of AAV8 and AAV9 vectors encoding human GLA in Gla knockout (Gla^−/y) mice by measuring α-Gal A activity and monitoring safety. To evaluate therapeutic efficacy, symptomatic Fabry mice (G3S^Tg/+Gla^−/y) were used. Results: AAV9-GLA produced significantly higher and more sustained enzyme activity than AAV8-GLA across plasma, liver, heart, and kidney. In symptomatic mice, AAV9-GLA achieved superior reductions in serum Gb3 and lyso-Gb3 levels, greater Gb3 clearance in heart and kidney tissues, and improved proteinuria. Anti-GLA IgG titers remained below threshold for the first four weeks and increased modestly by week eight, indicating a limited humoral immune response. No significant clinical signs or weight loss were observed in Gla^−/y mice over the 3.5-month study period, supporting the favorable safety profile of AAV-mediated gene therapy. Conclusions: These findings demonstrate that AAV9 provides enhanced biodistribution and therapeutic efficacy compared to AAV8, supporting its potential for the treatment of Fabry disease. Full article

Lysosomal storage diseases are caused by defective lysosomal function, such as impaired lysosomal enzyme activities, which include more than 70 different diseases. Although biomarkers and therapies have been developed to date for some of them, many others remain challenging to diagnose and treat. In this study, an elevated level of Globotriaosylsphingosine (Lyso-Gb3), an already known biomarker for Fabry disease, was confirmed in the knock-out cells of the GLA, GNPTAB, and PSAP genes and models for Fabry, mucolipidosis II/III (ML II/III), and combined saposin deficiency, respectively. Lyso-Gb3 was high in ML II/III patient skin fibroblasts compared with normal cells and was decreased after total lysosomal enzyme supplementation. There have been no useful biomarkers reported in ML II/III until now. This study shows that Lyso-Gb3 is elevated in ML II/III patient cells and is decreased by treatment, indicating that Lyso-Gb3 is a potential biomarker for ML II/III. Full article

To clarify the problem of outer cold gas accretion onto disk galaxies, we performed the panoramic spectroscopy of six compact galaxy groups to search for intergalactic gas flows. The groups selected are partly known to possess HI data obtained in the 21 cm line, and most of them contain a member galaxy revealing decoupled kinematics of gas and stars and thus having recently experienced a gas accretion event. Fabry-Perot scanning interferometry performed at the Russian 6 m telescope has provided us with the group maps at H$\alpha$ emission-line intensity and with ionized-gas velocity maps. We detected several intergalactic ionized-gas flows and some tidal outer ionized-gas structures; but none of them can be a source of gas accretion onto neighboring galaxies with decoupled gas–star kinematics. Only in a single case, that of NGC 7465, we can relate the inner inclined gaseous disk with the outer gas inflow; but the origin of this gas stream remains unknown—it does not originate from the neighboring NGC 7463 or NGC 7464. Full article