Histologic and ultrastructural study of intracranial Gaucheroma causing deafness in a patient with Gaucher disease type 3: Effects of substrate reduction therapy.

Hearing loss is frequently associated with Gaucher disease (GD). Gaucher cells are enlarged reticuloendothelial cells containing glucocerebroside in the lysosomes due to deficiency of the glucocerebrosidase. Gaucheromas consist of accumulated Gaucher cells. Gaucher cells accumulate in variable tissues including the liver, spleen, bone marrow, and the middle ear and the mastoid causing conductive hearing loss. Neurons and astrocytes in the central nervous system are affected in neuronopathic GD leading to sensorineural hearing loss. Gaucheromas can develop even in patients treated with enzyme replacement therapy (ERT). We report a 19-year-old female patient with GD type 3 who developed profound bilateral hearing loss associated with intracranial Gaucheroma. Combination therapy of ERT with imiglucerase and substrate reduction therapy (SRT) with eliglustat significantly decreased the size of Gaucher cells and cleared the characteristic microtubular structures in the lysosomes in Gaucher cells. Early implementation of SRT may prevent at least conductive hearing impairment in GD although it may not prevent sensorineural hearing loss due to inner hair cell dysfunction which is also known to be associated with neuronopathic GD.

Clinical outcomes in patients switching from agalsidase beta to migalastat: A Fabry Registry analysis.

Fabry Registry data were analyzed among 83 agalsidase beta-treated patients with Fabry disease who switched to migalastat. Outcomes (estimated glomerular filtration rate [eGFR], urine protein-creatinine ratio [UPCR], plasma globotriaosylceramide [GL-3], plasma globotriaosylsphingosine [lyso-GL-3], interventricular septal wall thickness [IVST], left posterior wall thickness [LPWT], left ventricular mass index [LVMI]) were assessed using linear mixed models to estimate annual change over time in the pre- and postswitch periods. eGFR decreased throughout both periods (preswitch: -0.85 mL/min/1.73 m2/year; postswitch: -1.96 mL/min/1.73 m2/year; both p < 0.0001), with steeper decline postswitch (ppre/post = 0.01) in both classic and late-onset patients. UPCR increased significantly postswitch (ppre/post = 0.003) among classic patients and was stable in both periods among late-onset patients. GL-3 trajectories worsened postswitch across phenotypes (ppre/post = 0.0005 classic, 0.02 late-onset). LPWT was stable preswitch (0.07 mm/year, p = 0.25) and decreased postswitch (-0.51 mm/year, p = 0.0005; ppre/post = 0.0009), primarily among late-onset patients. IVST and LVMI slopes varied significantly by phenotype. Among classic patients, IVST and LVMI were stable and decreasing, respectively preswitch and increasing postswitch (ppre/post = 0.02 IVST, 0.01 LVMI). Among late-onset patients, IVST significantly decreased postswitch (ppre/post = 0.0003); LVMI was stable over time (ppre/post = 0.89). Ultimately, eGFR and GL-3 trajectories worsened postswitch across phenotypes, while UPCR and cardiac measures worsened among classic and stabilized/improved among late-onset patients. These findings indicate variability in long-term outcomes after switching from ERT to migalastat, underscoring the importance of careful monitoring.

Twelve Years of the Gaucher Outcomes Survey (GOS): Insights, Achievements, and Lessons Learned from a Global Patient Registry.

Background: Long-term patient registries are important for evaluating treatment outcomes in patients with rare diseases, and can provide insights into natural disease history and progression in real-world clinical practice. Initiated in 2010, the Gaucher Outcome Survey (GOS) is an ongoing, international, multicenter, observational registry (ClinicalTrials.gov Identifier: NCT03291223) for patients with a diagnosis of Gaucher disease (GD), irrespective of treatment type or status, with a primary objective to monitor safety and long-term effectiveness of velaglucerase alfa. Methods: Here, we evaluated the GOS population 12 years after the registry initiation. Results: As of 25 February 2023, 2084 patients enrolled in the GOS and 1643 received GD-specific treatment. Patients exhibited broad heterogeneity at baseline: age of diagnosis (0 to 85.3 years), hemoglobin concentrations (<80.0 g/L to >150 g/L), platelet counts (<50 × 109/L to >450 × 109/L), and liver and spleen volumes. Most patients treated with enzyme replacement therapy or substrate reduction therapy reported improvements in clinical parameters within 1 year of treatment initiation, maintained over the course of treatment up to 12 years, whereas untreated patients had baseline values closer to standard reference thresholds and showed stability over time. Conclusion: The 12-year data from the GOS confirm the impact of long-term treatment with GD-specific agents and offer insights into disease progression and outcomes in a real-world setting.

Evaluation of a Ground Subsidence Zone in an Urban Area Using Geophysical Methods.

An important geological risk to which many towns in Puglia are exposed is sinking cavities in urban areas. For urban centers, studying, mapping, providing geological and speleological descriptions, classifying, and cataloging the forms and types of cavities is essential because cavities are linked to past local anthropic and natural processes at different sites. These circumstances could lead to the enhancement of existing underground cavities in urban areas through conservation and continuous monitoring. Unfortunately, in many cases, these underground cavities have been used as landfills and subsequently abandoned. In late March 2007, one of these cavities collapsed inside Gallipoli's inhabited center, causing damage to the structures but fortunately not human lives. In the area surrounding the collapsed cavity, a series of geophysical investigations were undertaken using ground penetrating radar in an attempt to delimit the area of collapse and develop possible interventions for restoration. In the same area, these measures were repeated 16 years later in December 2022 due to another collapse. The comparison between data acquired in these two periods shows that there were no strong changes apart from an increased presence of subsoil moisture in 2022.

Evidence of Lysosomal ß-Hexosaminidase Enzymatic Activity Associated with Extracellular Vesicles: Potential Applications for the Correction of Sandhoff Disease.

Extracellular vesicles (EVs) can be isolated from biological fluids and cell culture medium. Their nanometric dimension, relative stability, and biocompatibility have raised considerable interest for their therapeutic use as delivery vehicles of macromolecules, namely nucleic acids and proteins. Deficiency in lysosomal enzymes and associated proteins is at the basis of a group of genetic diseases known as lysosomal storage disorders (LSDs), characterized by the accumulation of undigested substrates into lysosomes. Among them, GM2 gangliosidoses are due to a deficiency in the activity of lysosomal enzyme ß-hexosaminidase, leading to the accumulation of the GM2 ganglioside and severe neurological symptoms. Current therapeutic approaches, including enzyme replacement therapy (ERT), have proven unable to significantly treat these conditions. Here, we provide evidence that the lysosomal ß-hexosaminidase enzyme is associated with EVs released by HEK cells and that the EV-associated activity can be increased by overexpressing the α-subunit of ß-hexosaminidase. The delivery of EVs to ß-hexosaminidase-deficient fibroblasts results in a partial cross-correction of the enzymatic defect. Overall findings indicate that EVs could be a source of ß-hexosaminidase that is potentially exploitable for developing therapeutic approaches for currently untreatable LSDs.

Patterns of electrical properties change of heavy metal-organic compound contaminated media in soil-groundwater systems: From laboratory experiments to site application.

Differences in electrical properties of media are the basis for determining the type and extent of contamination using geophysical methods. However, differences in heavy metals and organic matter complicate the electrical properties of compound-contaminated media, and existing geophysical methods cannot independently identify compound contamination. Therefore, this study proposes a geophysical detection system that combines electrical resistance tomography (ERT) and induced polarization methods and establishes a solid theory as the basis for the system application through laboratory experiments, model analysis, and site applications. The study reveals that as the organics volume proportion increases, the resistivity and normalized chargeability of contaminated media increased slowly, followed by a rapid increase, and finally reached a stable state. The specific type of compound significantly influences the electrical properties, while the resistivity of different kinds of compound-contaminated media reaches the same maximum value as the organics volume proportion increases. The medium type determines the contaminated media's lower resistivity limit and upper normalized chargeability limit. Additionally, the interplay between heavy metal type, content, and medium complicates the electrical properties of the media, with the compound type exerting a significant impact on resistivity. Archie's law and random forest modeling reveal that the inflection point for resistivity change occurs at 40 % and 80 % organics volume proportions, while the inflection point for normalized chargeability change occurs at 30 % and 70 % organics volume proportions in compound-contaminated media. These inflection points depend on the types of compounds, compositions, proportions, and media, and their importance for the electrical properties of the media changes with the increasing organics volume proportion. Based on the changing patterns of resistivity and normalized chargeability in heavy metal-organic compound contaminated media, the modified geophysical detection system can effectively identify the pollution type and intensity, which provides accurate pollution information to develop effective treatment strategies.

Effects of Enzyme Replacement Therapy on Cardiac MRI Findings in Fabry Disease: A Systematic Review and Meta-Analysis.

Purpose To perform a systematic review and meta-analysis to assess the effect of enzyme replacement therapy on cardiac MRI parameters in patients with Fabry disease. Materials and Methods A systematic literature search was conducted from January 1, 2000, through January 1, 2024, in PubMed, ClinicalTrials.gov, Embase, and Cochrane Library databases. Study outcomes were changes in the following parameters: (a) left ventricular wall mass (LVM), measured in grams; (b) LVM indexed to body mass index, measured in grams per meters squared; (c) maximum left ventricular wall thickness (MLVWT), measured in millimeters; (d) late gadolinium enhancement (LGE) extent, measured in percentage of LVM; and (e) native T1 mapping, measured in milliseconds. A random-effects meta-analysis of the pooled mean differences between baseline and follow-up parameters was conducted. The study protocol was registered in PROSPERO (CRD42022336223). Results The final analysis included 11 studies of a total of 445 patients with Fabry disease (mean age ± SD, 41 years ± 11; 277 male, 168 female). Between baseline and follow-up cardiac MRI, the following did not change: T1 mapping (mean difference, 6 msec [95% CI: -2, 15]; two studies, 70 patients, I2 = 88%) and LVM indexed (mean difference, -1 g/m2 [95% CI: -6, 3]; four studies, 290 patients, I2 = 81%). The following measures minimally decreased: LVM (mean difference, -18 g [95% CI: -33, -3]; seven studies, 107 patients, I2 = 96%) and MLVWT (mean difference, -1 mm [95% CI: -2, -0.02]; six studies, 151 patients, I2 = 90%). LGE extent increased (mean difference, 1% [95% CI: 1, 1]; three studies, 114 patients, I2 = 85%). Conclusion In patients with Fabry disease, enzyme replacement therapy was associated with stabilization of LVM, MLVWT, and T1 mapping values, whereas LGE extent mildly increased. Keywords: Fabry Disease, Enzyme Replacement Therapy (ERT), Cardiac MRI, Late Gadolinium Enhancement (LGE) Supplemental material is available for this article. © RSNA, 2024.

Long-Term Treatment of Gaucher Disease with Velaglucerase Alfa in ERT-Naïve Patients from the Gaucher Outcome Survey (GOS) Registry.

Background: Gaucher disease (GD) is a rare, autosomal, recessive condition characterized by hepatosplenomegaly, thrombocytopenia, anemia, and bone abnormalities, often requiring life-long treatment. Velaglucerase alfa has improved hematologic and visceral parameters in clinical trials; however, limited long-term efficacy and safety data are available. Methods: The Gaucher Outcome Survey (GOS), a structured and validated international registry for patients with confirmed GD, provides an opportunity to evaluate long-term data from patients receiving velaglucerase alfa. Results: This analysis included 376 treatment-naïve children and adults with GD enrolled in GOS, including 20 with type 3 GD, who initiated velaglucerase alfa through participation in clinical trials or as part of their clinical management and continued treatment for a mean (range) time of 6.6 (0.003-18.6) years. Initial improvements in hematologic and visceral parameters and the biomarkers glucosylsphingosine (lyso-GL1) and chitotriosidase were observed after one year of treatment and were maintained throughout the follow-up period. Of 129 (34.3%) patients who developed adverse events during the follow-up period, events were considered related to treatment in 33 (8.8%). None led to treatment discontinuation. There were 21 deaths overall, none of which were considered related to treatment. Conclusions: This analysis of data from the GOS registry supports the safety and efficacy of velaglucerase alfa in patients with GD.

Seeing beyond the symptoms: biomarkers and brain regions linked to cognitive decline in Alzheimer's disease.

Objective: Early Alzheimer's disease (AD) diagnosis remains challenging, necessitating specific biomarkers for timely detection. This study aimed to identify such biomarkers and explore their associations with cognitive decline. Methods: A cohort of 1759 individuals across cognitive aging stages, including healthy controls (HC), mild cognitive impairment (MCI), and AD, was examined. Utilizing nine biomarkers from structural MRI (sMRI), diffusion tensor imaging (DTI), and positron emission tomography (PET), predictions were made for Mini-Mental State Examination (MMSE), Clinical Dementia Rating Scale Sum of Boxes (CDRSB), and Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS). Biomarkers included four sMRI (e.g., average thickness [ATH]), four DTI (e.g., mean diffusivity [MD]), and one PET Amyloid-ß (Aß) measure. Ensemble regression tree (ERT) technique with bagging and random forest approaches were applied in four groups (HC/MCI, HC/AD, MCI/AD, and HC/MCI/AD). Results: Aß emerged as a robust predictor of cognitive scores, particularly in late-stage AD. Volumetric measures, notably ATH, consistently correlated with cognitive scores across early and late disease stages. Additionally, ADAS demonstrated links to various neuroimaging biomarkers in all subject groups, highlighting its efficacy in monitoring brain changes throughout disease progression. ERT identified key brain regions associated with cognitive scores, such as the right transverse temporal region for Aß, left and right entorhinal cortex, left inferior temporal gyrus, and left middle temporal gyrus for ATH, and the left uncinate fasciculus for MD. Conclusion: This study underscores the importance of an interdisciplinary approach in understanding AD mechanisms, offering potential contributions to early biomarker development.

Three-Dimensional ERT Advanced Detection Method with Source-Position Electrode Excitation for Tunnel-Boring Machines.

Tunnel-boring machines (TBMs) are widely used in urban underground tunnel construction due to their fast and efficient features. However, shield-tunnel construction faces increasingly complex geological environments and may encounter geological hazards such as faults, fracture zones, water surges, and collapses, which can cause significant property damage and casualties. Existing geophysical methods are subject to many limitations in the shield-tunnel environment, where the detection space is extremely small, and a variety of advanced detection methods are unable to meet the required detection requirements. Therefore, it is crucial to accurately detect the geological conditions in front of the tunnel face in real time during the tunnel boring process of TBM tunnels. In this paper, a 3D-ERT advanced detection method using source-position electrode excitation is proposed. First, a source-position electrode array integrated into the TBM cutterhead is designed for the shield-tunnel construction environment, which provides data security for the inverse imaging of the anomalous bodies. Secondly, a 3D finite element tunnel model containing high- and low-resistance anomalous bodies is established, and the GREIT reconstruction algorithm is utilized to reconstruct 3D images of the anomalous body in front of the tunnel face. Finally, a physical simulation experiment platform is built, and the effectiveness of the method is verified by laboratory physical modeling experiments with two different anomalous bodies. The results show that the position and shape of the anomalous body in front of the tunnel face can be well reconstructed, and the method provides a new idea for the continuous detection of shield construction tunnels with boring.

Modeling subsurface contaminant transport from a former open-pit uranium mine in fractured granites (La Ribière, France): Reducing uncertainties with geophysics.

The long-term management of tailings from former uranium (U) mines requires an in-depth understanding of the hydrogeological processes and water flow paths. In France, most of the legacy U mines are located in fractured crystalline (plutonic) rocks, where the intrinsic subsurface heterogeneity adds to the uncertainties about the former extraction and milling activities and the state of the mine when production was ceased. U ores were mainly processed by sulfuric acid leaching, leading to high-sulfate-content mill tailings now contained in several tailing storage facilities (TSFs). The La Ribière site, located in western central France, is a former open-pit and underground U mine, closed in 1992 and used to store mill tailings. This site is being used as a test case to establish a workflow in order to explain and predict water flow and subsurface contaminant transport. A conceptual model of water flow and sulfate transport, at the scale of the La Ribière watershed, is first developed based on available information and hydrogeochemical monitoring. Recent geophysical investigations allows refining this model. Electrical Resistivity Tomography (ERT) proves to be efficient at localizing the extent of the highly conductive sulfate plume inherited from the U-mill tailings, but also at imaging the weathering profile. Magnetic Resonance Sounding (MRS), despite the limited signal intensity due to the low porosity in crystalline rocks, gives some insight into the porosity values, the depth of the fractured layer and the location of the low-porosity ore-processing muds. Based on this conceptual model, a 3D flow and non-reactive transport model with the METIS code is developed and calibrated. This model allows predicting the evolution of the sulfate plume, but will also be used in future investigations, to build reactive transport models with simplified hydrogeology for U and other reactive contaminants.

A review on Gaucher disease: therapeutic potential of ß-glucocerebrosidase-targeted mRNA/saRNA approach.

Gaucher disease (GD), a rare hereditary lysosomal storage disorder, occurs due to a deficiency in the enzyme ß-glucocerebrosidase (GCase). This deficiency leads to the buildup of substrate glucosylceramide (GlcCer) in macrophages, eventually resulting in various complications. Among its three types, GD2 is particularly severe with neurological involvements. Current treatments, such as enzyme replacement therapy (ERT), are not effective for GD2 and GD3 due to their inability to cross the blood-brain barrier (BBB). Other treatment approaches, such as gene or chaperone therapies are still in experimental stages. Additionally, GD treatments are costly and can have certain side effects. The successful use of messenger RNA (mRNA)-based vaccines for COVID-19 in 2020 has sparked interest in nucleic acid-based therapies. Remarkably, mRNA technology also offers a novel approach for protein replacement purposes. Additionally, self-amplifying RNA (saRNA) technology shows promise, potentially producing more protein at lower doses. This review aims to explore the potential of a cost-effective mRNA/saRNA-based approach for GD therapy. The use of GCase-mRNA/saRNA as a protein replacement therapy could offer a new and promising direction for improving the quality of life and extending the lifespan of individuals with GD.

Women with Gaucher Disease.

Gaucher disease is an inherited disorder in which there is a deficiency of the enzyme glucocerebrosidase, which leads to the accumulation of glucosylceramide. Although much scientific evidence is now available, there is still limited data on the impact on the different life stages of women with this disease. Among other alterations, a delay in menarche has been described, although it has not been related to fertility problems. Menorrhagia is relatively frequent, being related to the presence of thrombocytopenia, thrombocytopathies or coagulation disorders. On the other hand, pregnancy planning is an increasingly frequent concern. All patients should undergo genetic counseling, and it is important to monitor the appearance or worsening of organomegaly, bone and hematologic abnormalities to establish clinical and therapeutic recommendations. Management during the puerperium will depend on the evolution of gestation, and, during the lactation period, the potential appearance of bone complications should be assessed. An early onset of menopause, compared to the general population, has also been described, which may accelerate the development of osteopenia. Finally, although the usual screening protocols for neoplasms are currently being performed, it is recommended to watch for early signs of liver or renal neoplasms when examining the results of imaging tests performed during evaluations for this disease.

Landslide assessment through integrated geoelectrical and seismic methods: A case study in Thungsong site, southern Thailand.

Many landslides can cause significant damage to infrastructure, property, and human life. To study landslide structure and processes, geophysical techniques are most productive when employed in combination with other survey and monitoring tools, such as intrusive sampling. Here, the integration of electrical resistivity tomography (ERT) and seismic refraction tomography (SRT) methods is used to assess landslides in Thungsong district, Nakhon Si Thammarat, the south of Thailand, where is a hilly and seasons of prolonged rainfall region. The 2D cross-plot analysis of P-wave velocity and resistivity values obtained by these two methods is introduced to identify potential landslide-prone zones in this region. The results of the 2D cross-plot model reveal detailed image of the subsurface conditions, highlighting areas of low P-wave velocity (lower than 600 m/s) and low resistivity (lower than 600 Ωm). These areas are indicative of weak zone and are potential to be sliding materials. Moreover, an intrusive sampling data from boreholes is also used for the calibration and validation geophysical data with geological data. This can improve the accuracy of landslide assessment and develop effective mitigation strategies to reduce the risk of landslides in this area. In addition of the 2D cross-plot, the volume of sliding material is also determined from the difference of the surface and slipping plane elevations. The volume calculation of sliding material is roughly 33447.76 m3. This approach provides a preliminary tool for landslide studies and monitoring landslides in this region, thus enabling an improved understanding of slope failure processes in this context, and the basis of a landslide mitigation strategy in the future.

Ribosomal profiling of human endogenous retroviruses in healthy tissues.

Human endogenous retroviruses (HERVs) are the germline embedded proviral fragments of ancient retroviral infections that make up roughly 8% of the human genome. Our understanding of HERVs in physiology primarily surrounds their non-coding functions, while their protein coding capacity remains virtually uncharacterized. Therefore, we applied the bioinformatic pipeline "hervQuant" to high-resolution ribosomal profiling of healthy tissues to provide a comprehensive overview of translationally active HERVs. We find that HERVs account for 0.1-0.4% of all translation in distinct tissue-specific profiles. Collectively, our study further supports claims that HERVs are actively translated throughout healthy tissues to provide sequences of retroviral origin to the human proteome.

An assessment of seismicity and near surface geophysical characteristics of potential solid waste landfill sites in the Eastern Black Sea Region of Türkiye.

This study aimed to assess the suitability of the potential solid waste landfill sites in seven provinces (Samsun, Ordu, Giresun, Trabzon, Gümüshane, Bayburt and Artvin) in the Eastern Blacksea Region of Türkiye. The earthquake hazard analysis for two major earthquakes which occurred in the region was first carried out. Then, the geophysical methods including seismic refraction tomography (SRT), electrical resistivity tomography (ERT) and Multichannel Analysis of Surface Waves (MASW) were conducted to find out the structural and physical properties of the subsurface which include the layering, soil classification based on VS30 and the groundwater content at 25 locations of 13 in target provinces. The integrated interpretation of whole data sets demonstrates that Isiktepe, Esence, Çamburnu and Kazantas which are characterized by VP > 1200 m/s, VS30 ≥ 400 m/s, ρ > 70 Ohm-m, low earthquake hazard and seismicity are more suitable among others. Vezirköprü, Sebinkarahisar, Yenice, Bayburt-Center, Balkaynak and Murgul will be suitable after a geotechnical reclamation due to moderate seismic velocities and electrical resistivity which are 900 < VP ≤ 1200 m/s, 200 < VS30 < 400 m/s and 10 < ρ ≤ 70 Ohm-m representing stiff and wet soils. In addition, Bafra, Agalik and Ovacik were considered to be unsuitable due to the presence of thick, water-saturated soft soil and extremely weathered rocks. Finally, this study shows that the joint interpretation of seismicity and geophysical data in potential waste landfill sites, extremely important for the planning and development of a city, can provide the valuable information which will enable to prevent possible deformations, environmental problems and economic losses after waste landfill.

Factors Associated With Successful Extubation Readiness Testing in Children With Congenital Heart Disease.

BACKGROUND: In children with congenital heart disease, extubation readiness testing (ERT) is performed to evaluate the potential for liberation from mechanical ventilation. There is a paucity of data that suggests what mechanical ventilation parameters are associated with successful ERT. We hypothesized that ERT success would be associated with certain mechanical ventilator parameters. METHODS: Data on daily ERT assessments were recorded as part of a quality improvement project. In accordance with our respiratory therapist-driven ventilator protocol, patients were assessed daily for ERT eligibility and tested daily, if eligible. Mechanical ventilation parameters were categorized a priori to evaluate the differences in levels of respiratory support. The primary outcome was ERT success. RESULTS: A total of 780 ERTs from 320 subjects (median [interquartile range] age 2.5 [0.6-6.5] months and median weight [interquartile range] 4.2 [3.3-6.9] kg) were evaluated. A total of 528 ERTs (68%) were passed, 306 successful ERTs (58%) resulted in extubation, and 30 subjects (9.4%) were re-intubated. There were statistically significant differences in the ERT pass rate for ventilator mode, peak inspiratory pressure, Δ pressure, PEEP, mean airway pressure ([Formula: see text]), and dead-space-to-tidal-volume ratio (all P < .001) but not for [Formula: see text]. ERT success decreased with increases in peak inspiratory pressure, Δ pressure, PEEP, [Formula: see text], and dead-space-to-tidal-volume ratio. Logistic regression revealed neonates, Δ pressure ≥ 11 cm H2O, and [Formula: see text] > 10 cm H2O were associated with a decreased odds of ERT success, whereas children ages 1-5 years and an [Formula: see text] of 0.31-0.40 had increased odds of ERT success. CONCLUSIONS: ERT pass rates decreased as ventilator support increased; however, some subjects were able to pass ERT despite high ventilator support. We found that [Formula: see text] was associated with ERT success and that protocols should consider using [Formula: see text] instead of PEEP thresholds for ERT eligibility. Cyanotic lesions were not associated with ERT success, which suggests that patients with cyanotic heart disease can be included in ERT protocols.

Real-time monitoring of in situ chemical oxidation (ISCO) of dissolved TCE by integrating electrical resistivity tomography and reactive transport modeling.

Successful in situ chemical oxidation (ISCO) applications require real-time monitoring to assess the oxidant delivery and treatment effectiveness, and to support rapid and cost-effective decision making. Existing monitoring methods often suffer from poor spatial coverage given a limited number of boreholes in most field conditions. The ionic nature of oxidants (e.g., permanganate) makes time-lapse electrical resistivity tomography (ERT) a potential monitoring tool for ISCO. However, time-lapse ERT is usually limited to qualitative analysis because it cannot distinguish between the electrical responses of the ionic oxidant and the ionic products from contaminant oxidation. This study proposed a real-time quantitative monitoring approach for ISCO by integrating time-lapse ERT and physics-based reactive transport models (RTM). Moving past common practice, where an electrical-conductivity anomaly in an ERT survey would be roughly linked to concentrations of anything ionic, we used PHT3D as our RTM to distinguish the contributions from the ionic oxidant and the ionic products and to quantify the spatio-temporal evolution of all chemical components. The proposed approach was evaluated through laboratory column experiments for trichloroethene (TCE) remediation. This ISCO experiment was monitored by both time-lapse ERT and downstream sampling. We found that changes in inverted bulk electrical conductivity, unsurprisingly, did not correlate well with the observed permanganate concentrations due to the ionic products. By integrating time-lapse ERT and RTM, the distribution of all chemical components was satisfactorily characterized and quantified. Measured concentration data from limited locations and the non-intrusive ERT data were found to be complementary for ISCO monitoring. The inverted bulk conductivity data were effective in capturing the spatial distribution of ionic species, while the concentration data provided information regarding dissolved TCE. Through incorporating multi-source data, the error of quantifying ISCO efficiency was kept at most 5 %, compared to errors that can reach up to 68 % when relying solely on concentration data.

Use of T1 mapping in cardiac MRI for the follow-up of Fabry disease in a pediatric population.

Background: Fabry disease (FD) is a rare X-linked lysosomal disorder caused by pathogenic variants in the alpha-galactosidase-A gene (GLA). Life threatening complications in adulthood include chronic kidney failure, strokes and the cardiac involvement which is the leading cause of mortality. Usually, it presents with hypertrophic cardiomyopathy, together with arrhythmia and conduction abnormalities. An early indicator is decreased T1 value on cardiac magnetic resonance (CMR). Enzyme replacement therapy (ERT) is effective on some extra-cardiac symptoms but its effect on cardiac lesions depends on the level of initial myocardial lesions. CMR is routinely used to monitor cardiac involvement in FD due to its capacity for tissular characterization. However, there is a lack of data on the pediatric population to understand how to integrate CMR into early therapeutic decisions. Method: Monocentric longitudinal study carried out at Montpellier University Hospital from 2016 to 2022. All pediatric patients with FD were evaluated over time with clinical, biological, and cardiac imaging (CMR, echocardiography). Results: Out of the six patients included, (3 males), five were treated with ERT during the study. Low T1 values were observed in 4 patients. The normalization of T1 values was observed after 4 years of ERT in 3 patients. Conclusion: Due to the lack of strong clinical and biological markers of FD in pediatric patients, initiation and follow-up of ERT efficacy remain challenging. CMR with T1-mapping, a noninvasive method, could play a role in the evaluation of early cardiac impairment in young patients at diagnosis and during follow-up with or without ERT.