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1.
Cell ; 169(5): 878-890.e15, 2017 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-28525755

RESUMEN

Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has limited their use against other divergent ebolaviruses associated with human disease. Here, we mined the human immune response to natural EBOV infection and identified mAbs with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. These mAbs recognize an inter-protomer epitope in the GP fusion loop, a critical and conserved element of the viral membrane fusion machinery, and neutralize viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GPCL) generated in host cell endosomes. Only a few somatic hypermutations are required for broad antiviral activity, and germline-approximating variants display enhanced GPCL recognition, suggesting that such antibodies could be elicited more efficiently with suitably optimized GP immunogens. Our findings inform the development of both broadly effective immunotherapeutics and vaccines against filoviruses.


Asunto(s)
Anticuerpos Neutralizantes/aislamiento & purificación , Anticuerpos Antivirales/aislamiento & purificación , Vacunas contra el Virus del Ébola/inmunología , Fiebre Hemorrágica Ebola/inmunología , Sobrevivientes , Secuencia de Aminoácidos , Animales , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/química , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/química , Anticuerpos Antivirales/inmunología , Chlorocebus aethiops , Reacciones Cruzadas , Ebolavirus/clasificación , Ebolavirus/inmunología , Femenino , Hurones , Fiebre Hemorrágica Ebola/virología , Humanos , Cinética , Ratones , Ratones Endogámicos BALB C , Modelos Moleculares , Alineación de Secuencia , Células Vero
2.
Brief Bioinform ; 25(3)2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38557673

RESUMEN

IMPRINTS-CETSA (Integrated Modulation of Protein Interaction States-Cellular Thermal Shift Assay) provides a highly resolved means to systematically study the interactions of proteins with other cellular components, including metabolites, nucleic acids and other proteins, at the proteome level, but no freely available and user-friendly data analysis software has been reported. Here, we report IMPRINTS.CETSA, an R package that provides the basic data processing framework for robust analysis of the IMPRINTS-CETSA data format, from preprocessing and normalization to visualization. We also report an accompanying R package, IMPRINTS.CETSA.app, which offers a user-friendly Shiny interface for analysis and interpretation of IMPRINTS-CETSA results, with seamless features such as functional enrichment and mapping to other databases at a single site. For the hit generation part, the diverse behaviors of protein modulations have been typically segregated with a two-measure scoring method, i.e. the abundance and thermal stability changes. We present a new algorithm to classify modulated proteins in IMPRINTS-CETSA experiments by a robust single-measure scoring. In this way, both the numerical changes and the statistical significances of the IMPRINTS information can be visualized on a single plot. The IMPRINTS.CETSA and IMPRINTS.CETSA.app R packages are freely available on GitHub at https://github.com/nkdailingyun/IMPRINTS.CETSA and https://github.com/mgerault/IMPRINTS.CETSA.app, respectively. IMPRINTS.CETSA.app is also available as an executable program at https://zenodo.org/records/10636134.


Asunto(s)
Aplicaciones Móviles , Programas Informáticos , Proteoma , Algoritmos , Proyectos de Investigación
3.
Nature ; 587(7834): 460-465, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33149301

RESUMEN

Atrial fibrillation, the most common cardiac arrhythmia, is an important contributor to mortality and morbidity, and particularly to the risk of stroke in humans1. Atrial-tissue fibrosis is a central pathophysiological feature of atrial fibrillation that also hampers its treatment; the underlying molecular mechanisms are poorly understood and warrant investigation given the inadequacy of present therapies2. Here we show that calcitonin, a hormone product of the thyroid gland involved in bone metabolism3, is also produced by atrial cardiomyocytes in substantial quantities and acts as a paracrine signal that affects neighbouring collagen-producing fibroblasts to control their proliferation and secretion of extracellular matrix proteins. Global disruption of calcitonin receptor signalling in mice causes atrial fibrosis and increases susceptibility to atrial fibrillation. In mice in which liver kinase B1 is knocked down specifically in the atria, atrial-specific knockdown of calcitonin promotes atrial fibrosis and increases and prolongs spontaneous episodes of atrial fibrillation, whereas atrial-specific overexpression of calcitonin prevents both atrial fibrosis and fibrillation. Human patients with persistent atrial fibrillation show sixfold lower levels of myocardial calcitonin compared to control individuals with normal heart rhythm, with loss of calcitonin receptors in the fibroblast membrane. Although transcriptome analysis of human atrial fibroblasts reveals little change after exposure to calcitonin, proteomic analysis shows extensive alterations in extracellular matrix proteins and pathways related to fibrogenesis, infection and immune responses, and transcriptional regulation. Strategies to restore disrupted myocardial calcitonin signalling thus may offer therapeutic avenues for patients with atrial fibrillation.


Asunto(s)
Arritmias Cardíacas/metabolismo , Calcitonina/metabolismo , Fibrinógeno/biosíntesis , Atrios Cardíacos/metabolismo , Miocardio/metabolismo , Comunicación Paracrina , Animales , Arritmias Cardíacas/patología , Arritmias Cardíacas/fisiopatología , Fibrilación Atrial , Colágeno Tipo I/metabolismo , Femenino , Fibroblastos/metabolismo , Fibrosis/metabolismo , Fibrosis/patología , Atrios Cardíacos/citología , Atrios Cardíacos/patología , Atrios Cardíacos/fisiopatología , Humanos , Masculino , Ratones , Miocardio/citología , Miocardio/patología , Miocitos Cardíacos/metabolismo , Receptores de Calcitonina/metabolismo
4.
Methods ; 224: 10-20, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38295893

RESUMEN

AMPs are short, mainly cationic membrane-active peptides found in all living organism. They perform diverse roles including signaling and acting as a line of defense against bacterial infections. AMPs have been extensively investigated as templates to facilitate the development of novel antimicrobial therapeutics. Understanding the interplay between these membrane-active peptides and the lipid membranes is considered to be a significant step in elucidating the specific mechanism of action of AMPs against prokaryotic and eukaryotic cells to aid the development of new therapeutics. In this review, we have provided a brief overview of various NMR techniques commonly used for studying AMP structure and AMP-membrane interactions in model membranes and whole cells.


Asunto(s)
Péptidos Catiónicos Antimicrobianos , Péptidos Antimicrobianos , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/análisis , Péptidos Catiónicos Antimicrobianos/química , Membrana Celular/química , Espectroscopía de Resonancia Magnética/métodos
5.
J Am Chem Soc ; 146(23): 15860-15868, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38814791

RESUMEN

Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is a benchmark hole-transporting (p-type) polymer that finds applications in diverse electronic devices. Most of its success is due to its facile synthesis in water, exceptional processability from aqueous solutions, and outstanding electrical performance in ambient. Applications in fields like (opto-)electronics, bioelectronics, and energy harvesting/storage devices often necessitate the complementary use of both p-type and n-type (electron-transporting) materials. However, the availability of n-type materials amenable to water-based polymerization and processing remains limited. Herein, we present a novel synthesis method enabling direct polymerization in water, yielding a highly conductive, water-processable n-type conjugated polymer, namely, poly[(2,2'-(2,5-dihydroxy-1,4-phenylene)diacetic acid)-stat-3,7-dihydrobenzo[1,2-b:4,5-b']difuran-2,6-dione] (PDADF), with remarkable electrical conductivity as high as 66 S cm-1, ranking among the highest for n-type polymers processed using green solvents. The new n-type polymer PDADF also exhibits outstanding stability, maintaining 90% of its initial conductivity after 146 days of storage in air. Our synthetic approach, along with the novel polymer it yields, promises significant advancements for the sustainable development of organic electronic materials and devices.

6.
Antimicrob Agents Chemother ; 68(7): e0160123, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38829050

RESUMEN

We examined the correlation between three different methods of Mycobacterium tuberculosis quantification: time to positivity (TTP), log10 CFU, and an assay to detect differentially detectable M. tuberculosis (DD Mtb) from three different prospective studies. Participants with DD Mtb have significantly more variation in the CFU/TTP correlation than participants with no DD Mtb (P < 0.001). This may impact the design of early bactericidal activity studies that use TTP as the primary outcome.


Asunto(s)
Carga Bacteriana , Mycobacterium tuberculosis , Mycobacterium tuberculosis/efectos de los fármacos , Humanos , Carga Bacteriana/métodos , Estudios Prospectivos , Masculino , Adulto , Femenino
7.
Ann Surg ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38887938

RESUMEN

OBJECTIVE: To analyse outcomes after adult right ex-situ split graft liver transplantations (RSLT) and compare with available outcome benchmarks from whole liver transplantation (WLT). SUMMARY BACKGROUND DATA: Ex-situ SLT may be a valuable strategy to tackle the increasing graft shortage. Recently established outcome benchmarks in WLT offer a novel reference to perform a comprehensive analysis of results after ex-situ RSLT. METHODS: This retrospective multicenter cohort study analyzes all consecutive adult SLT performed using right ex-situ split grafts from 01.01.2014 to 01.06.2022. Study endpoints included 1 year graft and recipient survival, overall morbidity expressed by the comprehensive complication index (CCI©) and specific post-LT complications. Results were compared to the published benchmark outcomes in low-risk adult WLT scenarii. RESULTS: In 224 adult right ex-situ SLT, 1y recipient and graft survival rates were 96% and 91.5%, within the WLT benchmarks. The 1y overall morbidity was also within the WLT benchmark (41.8 CCI points vs. <42.1). Detailed analysis, revealed cut surface bile leaks (17%, 65.8% Grade IIIa) as a specific complication without a negative impact on graft survival. There was a higher rate of early hepatic artery thrombosis (HAT) after SLT, above the WLT benchmark (4.9% vs. ≤4.1%), with a significant impact on early graft but not patient survival. CONCLUSION: In this multicentric study of right ex-situ split graft LT, we report 1-year overall morbidity and mortality rates within the published benchmarks for low-risk WLT. Cut surface bile leaks and early HAT are specific complications of SLT and should be acknowledged when expanding the use of ex-situ SLT.

8.
Oncologist ; 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38970398

RESUMEN

BACKGROUND: Currently available predictive models for chemotherapy-related toxicity are not sufficiently discriminative in older patients with cancer and do not consider moderate toxicities. The purpose of this study was to identify factors associated with moderate and severe chemotherapy toxicities in older patients with cancer. MATERIALS AND METHODS: Patients aged 70+ recruited in the prospective ELCAPA cohort were analyzed. A total of 837 patients with data on toxicities had received chemotherapy without other systemic treatment and were included between 2015 and 2022. To adjust for any imbalances in the distribution of covariates between patients receiving single-agent chemotherapy vs combination chemotherapy, we applied overlap weighting (a propensity-score-based technique). We used multinomial logistic regression. RESULTS: Median (interquartile range) age was 81 (77-84). Forty-one percent experienced moderate toxicity, and 33% experienced severe toxicity. Hematologic toxicities accounted for 53% of severe toxicities and 66% of moderate toxicities. Age <80 years, cancer type, metastatic status, Eastern Cooperative Oncology Group performance status (ECOG-PS) >1, no cognitive impairment were associated with combination chemotherapy decision. In a univariate analysis with overlap weighting, no factors were associated with moderate toxicity. Hemoglobin < 0 g/dL and a CIRS-G score >12 were associated with severe toxicity. In a multivariate analysis, only hemoglobin < 10 g/dL was independently associated with severe toxicity, adjusted OR 2.96 (95% CI, 1.20-7.29). CONCLUSION: By addressing indication bias for combination chemotherapy decision, only anemia and not cancer type, combination chemotherapy was predicting for severe chemotherapy-related toxicity in older patients with cancer. We did not find any predictors of moderate chemotherapy-related toxicity.

9.
Liver Transpl ; 30(8): 805-815, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38466885

RESUMEN

The purpose of this study was to propose an innovative intraoperative criterion in a liver transplantation setting that would judge arterial flow abnormality that may lead to early hepatic arterial occlusion, that is, thrombosis or stenosis, when left untreated and to carry out reanastomosis. After liver graft implantation, and after ensuring that there is no abnormality on the Doppler ultrasound (qualitative and quantitative assessment), we intraoperatively injected indocyanine green dye (0.01 mg/Kg), and we quantified the fluorescence signal at the graft pedicle using ImageJ software. From the obtained images of 89 adult patients transplanted in our center between September 2017 and April 2019, we constructed fluorescence intensity curves of the hepatic arterial signal and examined their relationship with the occurrence of early hepatic arterial occlusion (thrombosis or stenosis). Early hepatic arterial occlusion occurred in 7 patients (7.8%), including 3 thrombosis and 4 stenosis. Among various parameters of the flow intensity curve analyzed, the ratio of peak to plateau fluorescence intensity and the jagged wave pattern at the plateau phase were closely associated with this dreaded event. By combining the ratio of peak to plateau at 0.275 and a jagged wave, we best predicted the occurrence of early hepatic arterial occlusion and thrombosis, with sensitivity/specificity of 0.86/0.98 and 1.00/0.94, respectively. Through a simple composite parameter, the indocyanine green fluorescence imaging system is an additional and promising intraoperative modality for identifying recipients of transplant at high risk of developing early hepatic arterial occlusion. This tool could assist the surgeon in the decision to redo the anastomosis despite normal Doppler ultrasonography.


Asunto(s)
Arteria Hepática , Verde de Indocianina , Trasplante de Hígado , Imagen Óptica , Trombosis , Humanos , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Verde de Indocianina/administración & dosificación , Arteria Hepática/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Imagen Óptica/métodos , Trombosis/etiología , Trombosis/diagnóstico por imagen , Anciano , Adulto , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/diagnóstico , Ultrasonografía Doppler/métodos , Valor Predictivo de las Pruebas , Arteriopatías Oclusivas/etiología , Arteriopatías Oclusivas/diagnóstico por imagen , Arteriopatías Oclusivas/diagnóstico , Arteriopatías Oclusivas/cirugía , Hígado/diagnóstico por imagen , Hígado/irrigación sanguínea , Hígado/cirugía , Colorantes/administración & dosificación , Constricción Patológica/etiología , Monitoreo Intraoperatorio/métodos , Estudios Retrospectivos , Cuidados Intraoperatorios/métodos
10.
Mol Syst Biol ; 19(5): e11443, 2023 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-36942755

RESUMEN

Metabolism is controlled to ensure organismal development and homeostasis. Several mechanisms regulate metabolism, including allosteric control and transcriptional regulation of metabolic enzymes and transporters. So far, metabolism regulation has mostly been described for individual genes and pathways, and the extent of transcriptional regulation of the entire metabolic network remains largely unknown. Here, we find that three-quarters of all metabolic genes are transcriptionally regulated in the nematode Caenorhabditis elegans. We find that many annotated metabolic pathways are coexpressed, and we use gene expression data and the iCEL1314 metabolic network model to define coregulated subpathways in an unbiased manner. Using a large gene expression compendium, we determine the conditions where subpathways exhibit strong coexpression. Finally, we develop "WormClust," a web application that enables a gene-by-gene query of genes to view their association with metabolic (sub)-pathways. Overall, this study sheds light on the ubiquity of transcriptional regulation of metabolism and provides a blueprint for similar studies in other organisms, including humans.


Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animales , Humanos , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Regulación de la Expresión Génica , Programas Informáticos
11.
J Med Virol ; 96(8): e29836, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39078052

RESUMEN

Primary effusion lymphoma (PEL) is a rare B-cell non-Hodgkin lymphoma associated with Kaposi Sarcoma-associated herpesvirus (KSHV/HHV8) infection. Lymphoma cells are coinfected with Epstein-Barr virus (EBV) in 60-80% of cases. Tools allowing a reliable PEL diagnosis are lacking. This study reports PEL diagnosis in 4 patients using a Flow-Fluorescence in situ hybridization (FlowFISH) technique that allowed detection of differentially expressed EBV and HHV8 transcripts within the same sample, revealing viral heterogeneity of the disease. Moreover, infected cells exhibited variable expressions of CD19, CD38, CD40, and CD138. Therefore, FlowFISH is a promising tool to diagnose and characterize complex viral lymphoproliferations.


Asunto(s)
Herpesvirus Humano 4 , Herpesvirus Humano 8 , Hibridación Fluorescente in Situ , Linfoma de Efusión Primaria , Humanos , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/aislamiento & purificación , Hibridación Fluorescente in Situ/métodos , Linfoma de Efusión Primaria/virología , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Masculino , Anciano , Persona de Mediana Edad , Femenino , Infecciones por Herpesviridae/virología , Infecciones por Herpesviridae/diagnóstico , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Anciano de 80 o más Años
12.
Ann Surg Oncol ; 31(10): 6485-6494, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38592622

RESUMEN

BACKGROUND: Hypothermic liver perfusion decreases ischemia/reperfusion injury during hepatectomy under standard total vascular exclusion (TVE) of the liver. This surgery needs venovenous bypass and is hampered by high morbi-mortality. TVE preserving the inferior vena cava (IVC) flow is hemodynamically well tolerated but remains limited in duration when performed under liver normothermia. The objective of this study was to report the results of TVE preserving the caval flow, modified to allow hypothermic liver perfusion and obviate splanchnic congestion. PATIENTS AND METHODS: The technique, indicated for tumors abutting large tributaries of the hepatic veins but sparing their roots in IVC and the latter, was applied when TVE was anticipated to last for ≥ 60 min. It combines continuous TVE preserving the IVC flow with hypothermic liver perfusion and temporary portacaval shunt (PCS). Results are given as median (range). RESULTS: Vascular control was achieved in 13 patients with excellent hemodynamical tolerance. PCS was direct or via an interposed synthetic graft (five and eight cases, respectively). Liver temperature dropped to 16.5 (6-24) °C under perfusion of 2 (2-4) L of cold perfusate. TVE lasted 67 (54-125) min and 4.5 (0-8) blood units were transfused. Resection was major in nine cases and was complete in all cases. Five complications occurred in four patients, and the 90-day mortality rate was zero. CONCLUSIONS: This technique maintains stable hemodynamics and combines the advantages of in situ or ex situ standard TVE with hypothermic liver perfusion, without their inherent prolongation of ischemia time and need for venovenous bypass.


Asunto(s)
Hepatectomía , Hipotermia Inducida , Neoplasias Hepáticas , Perfusión , Derivación Portocava Quirúrgica , Vena Cava Inferior , Humanos , Hepatectomía/métodos , Derivación Portocava Quirúrgica/métodos , Vena Cava Inferior/cirugía , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Anciano , Hipotermia Inducida/métodos , Perfusión/métodos , Adulto , Prueba de Estudio Conceptual , Estudios de Seguimiento , Pronóstico , Hígado/cirugía , Hígado/irrigación sanguínea , Venas Hepáticas/cirugía
13.
Phys Rev Lett ; 132(15): 150607, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38682990

RESUMEN

The Gottesman-Kitaev-Preskill (GKP) code encodes a logical qubit into a bosonic system with resilience against single-photon loss, the predominant error in most bosonic systems. Here we present experimental results demonstrating quantum error correction of GKP states based on reservoir engineering of a superconducting device. Error correction is made fully autonomous through an unconditional reset of an auxiliary transmon qubit. We show that the lifetime of the logical qubit is increased from quantum error correction, therefore reaching the point at which more errors are corrected than generated.

14.
Malar J ; 23(1): 22, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38229097

RESUMEN

BACKGROUND: Chronic carriage of asymptomatic low-density Plasmodium falciparum parasitaemia in the dry season may support maintenance of acquired immunity that protects against clinical malaria. However, the relationship between chronic low-density infections and subsequent risk of clinical malaria episodes remains unclear. METHODS: In a 2-years study (December 2014 to December 2016) in eastern Gambia, nine cross-sectional surveys using molecular parasite detection were performed in the dry and wet season. During the 2016 malaria transmission season, passive case detection identified episodes of clinical malaria. RESULTS: Among the 5256 samples collected, 444 (8.4%) were positive for P. falciparum. A multivariate model identified village of residence, male sex, age ≥ 5 years old, anaemia, and fever as independent factors associated with P. falciparum parasite carriage. Infections did not cluster over time within the same households or recurred among neighbouring households. Asymptomatic parasite carriage at the end of dry season was associated with a higher risk of infection (Hazard Ratio, HR = 3.0, p < 0.0001) and clinical malaria (HR = 1.561, p = 0.057) during the following transmission season. Age and village of residence were additional predictors of infection and clinical malaria during the transmission season. CONCLUSION: Chronic parasite carriage during the dry season is associated with an increased risk of malaria infection and clinical malaria. It is unclear whether this is due to environmental exposure or to other factors.


Asunto(s)
Malaria Falciparum , Malaria , Masculino , Humanos , Preescolar , Plasmodium falciparum , Estaciones del Año , Gambia/epidemiología , Estudios Transversales , Malaria Falciparum/diagnóstico , Prevalencia
15.
J Endovasc Ther ; : 15266028241284034, 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39323372

RESUMEN

PURPOSE: This study aims to assess the safety and efficacy of the fenestrated Anaconda device for the treatment of complex aortic aneurysms over 1 year in daily clinical practice. MATERIALS AND METHODS: All patients who received the graft between October 2019 and October 2020 were prospectively enrolled in an observational, multicenter national registry. The primary endpoint was the aneurysm-related 1-year mortality rate. Secondary endpoints included all-cause mortality, technical success, device-related adverse events (AEs) and major complications, secondary reinterventions, endoleaks, target vessel (TV) outcomes, and a center-volume analysis comparing mortality and secondary reintervention rate between expert centers (>15 F/BEVAR per year) and nonexpert centers (≤15 F/BEVAR per year). RESULTS: Ninety-seven patients from 28 centers were treated. Aneurysms types included juxta-renal and short neck (84.6%), pararenal (5.2%), paravisceral (3.1%), and type IV thoracoabdominal (2.5%). Configurations with 1, 2, 3, and 4 fenestrations were used in 2, 12, 18, and 65 cases, respectively, totaling 350 TVs. Technical success was 98.0%, with 1 type Ic and 1 type IIIc endoleak. Mean follow-up was 468 days. Ten patients died, with 8 deaths (8.2%) due to non-aortic causes and 2 deaths (2.1%) from unknown causes. The estimated 1-year survival rate was 92.7% (95% CI: 87.8-98.1%). The reintervention rate at 30 days was 11.3% and the estimated reintervention rate at 1 year was 21.6% (95% CI: 12.7-29.6%). No type Ia endoleak occurred during follow-up. Three type III endoleaks occurred and required reintervention. Three TV occlusion occurred, yielding a 1-year TVI-free rate of 92.4% (95% CI: 89.4-99.3). No device-related major complication was recorded, and 3 device-related AEs occurred: 1 limb migration, 1 limb kinking and 1 limb thrombosis. There was no statistically significant difference in mortality and survival without reintervention between expert and nonexpert centers (Log rank p=0.52 and p=0.16, respectively). CONCLUSION: The fenestrated Anaconda device demonstrated acceptable early and at 1-year safety and efficacy for treating primarily juxta-renal and short-neck aortic aneurysms, in centers with varying levels of experience. CLINICAL IMPACT: The Anaconda Fenestrated, as the second commercially available custom-made device for complex endovascular aortic surgery, might adress some anatomical challenges. Following market authorization, this registry presents the 1-year outcomes of real-world device usage in a large number of centers, including small clinics. The results indicate that the device provided adequate efficacy and safety for treating mostly juxta-renal and short neck aneurysms, with notable improvement in technical success rate compared to older reports.

16.
J Pediatr Hematol Oncol ; 46(5): e331-e333, 2024 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-38652075

RESUMEN

Multiple myeloma is a rare disease in pediatrics, where about 30 cases are described under 15 years old. It is even rarer when atypical multiple myeloma occurs in the context of autoimmunity. This case describes a 9-year-old female with autoimmune lymphoproliferative-like disease and combined immune deficiency that developed acute kidney failure with monoclonal peak associated with RAC2 and TNFRSF9 variants. An adapted protocol from the backbone adult multiple myeloma standard of care with the addition of an allogeneic hematopoietic stem cell transplant was used. The patient, now nearly a year posttransplant, shows 100% chimerism with no sign of relapse.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Humanos , Femenino , Niño , Lesión Renal Aguda/etiología , Lesión Renal Aguda/patología , Mieloma Múltiple/complicaciones , Mieloma Múltiple/patología , Síndrome Linfoproliferativo Autoinmune/complicaciones , Síndrome Linfoproliferativo Autoinmune/patología , Síndrome Linfoproliferativo Autoinmune/diagnóstico , Síndrome Linfoproliferativo Autoinmune/genética
17.
Artículo en Inglés | MEDLINE | ID: mdl-39382201

RESUMEN

INTRODUCTION: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome with utero-vaginal aplasia is the most severe form of the Müllerian duct anomalies and can be associated with extra-genital abnormalities such as renal or skeletal anomalies, hearing loss, or cardiac defects. The past two decades have witnessed significant advances both in understanding the etiologies of MRKH and in the development of fertility treatments such as uterine transplantation. The present work aimed to determine the rate of women with MRKH syndrome who underwent optimal initial management (after comprehensive malformation assessment) and to establish the rate of patients eligible for uterine transplantation (i.e., those with a vaginal length ≥7 cm without reconstruction using a bowel segment, and an anti-Müllerian hormone level >1.5 ng/mL before 35 years). MATERIAL AND METHODS: Cohort study of 85 women with MRKH syndrome consulting in our tertiary center. RESULTS: 62.4% of women with MRKH syndrome had an exhaustive malformative evaluation according to the French guidelines (Protocole National de Diagnostic et de Soin [PNDS]), of which 76.5% had associated malformations (MRKH type II). Pedigree, when available, showed a family history of infertility or a urogenital tract spectrum anomaly in 60% of cases. Concerning the uterine transplantation selection criteria, when evaluated, 22.6% of women had an anti-Müllerian hormone level <1.5 ng/mL and 36% a vaginal length <7 cm. On the 21 women with complete evaluation of both primary and secondary outcomes, 14 of them would be eligible for a uterine transplantation program at the time of consultation according to the main inclusion criteria of uterine transplantation program. CONCLUSIONS: Women with MRKH syndrome are often inadequately explored for associated malformations. Early assessment and monitoring of the ovarian reserve is key for fertility preservation, especially in the era of uterine transplantation.

18.
Curr Cardiol Rep ; 26(6): 601-622, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38625456

RESUMEN

PURPOSE OF REVIEW: Invasive cardiologists are exposed to large amounts of ionizing radiation. This review aims to summarize the main occupational risks in a radiation-exposed cardiology practice. RECENT FINDINGS: We carried out a literature review on the subject. The studies reviewed allowed us to list six main health risk categories possibly associated with radiation exposure among cardiologists: deoxyribonucleic acid (DNA) and biochemical damages; cancers; ocular manifestations; olfaction, vascular, and neuropsychological alterations; musculoskeletal problems; and reproductive risks. Our descriptive analysis demonstrates higher risks of DNA damage and lens opacities among radiation-exposed cardiology staff. Surveys and questionnaires have demonstrated a higher risk of musculoskeletal disease in exposed workers. Studies reported no difference in cancer frequency between radiation-exposed workers and controls. Changes in olfactory performance, neuropsychological aspects, and vascular changes have also been reported. Limited literature supports the security of continuing radiation-exposed work during pregnancy. Therefore, there is an urgent need to increase knowledge of the occupational risks of radiation exposure and to adopt technologies to reduce them.


Asunto(s)
Cardiólogos , Exposición Profesional , Exposición a la Radiación , Humanos , Exposición Profesional/efectos adversos , Exposición a la Radiación/efectos adversos , Traumatismos por Radiación/etiología , Enfermedades Profesionales/etiología , Radiación Ionizante , Factores de Riesgo , Daño del ADN/efectos de la radiación
19.
Int J Mol Sci ; 25(17)2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39273094

RESUMEN

Ultraviolet (UV) exposure and atmospheric pollution are both independently implicated in skin diseases such as cancer and premature aging. UVA wavelengths, which penetrate in the deep layers of the skin dermis, exert their toxicity mainly through chromophore photosensitization reactions. Benzo[a]pyrene (BaP), the most abundant polycyclic aromatic hydrocarbon originating from the incomplete combustion of organic matter, could act as a chromophore and absorb UVA. We and other groups have previously shown that BaP and UVA synergize their toxicity in skin cells, which leads to important oxidation. Even if mitochondria alterations have been related to premature skin aging and other skin disorders, no studies have focused on the synergy between UV exposure and pollution on mitochondria. Our study aims to investigate the combined effect of UVA and BaP specifically on mitochondria in order to assess the effect on mitochondrial membranes and the consequences on mitochondrial activity. We show that BaP has a strong affinity for mitochondria and that this affinity leads to an important induction of lipid peroxidation and membrane disruption when exposed to UVA. Co-exposure to UVA and BaP synergizes their toxicity to negatively impact mitochondrial membrane potential, mitochondrial metabolism and the mitochondrial network. Altogether, our results highlight the implication of mitochondria in the synergistic toxicity of pollution and UV exposure and the potential of this toxicity on skin integrity.


Asunto(s)
Benzo(a)pireno , Peroxidación de Lípido , Mitocondrias , Rayos Ultravioleta , Rayos Ultravioleta/efectos adversos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de la radiación , Benzo(a)pireno/toxicidad , Humanos , Peroxidación de Lípido/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Piel/efectos de los fármacos , Piel/efectos de la radiación , Piel/metabolismo
20.
Int J Environ Health Res ; 34(10): 3586-3599, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38332610

RESUMEN

Decentralized water systems (DWS) distribute water in remote African areas. Throughout an intervention in Maniema, Congo, the influence of a DWS performing chlorination in the community's water quality was measured. Additionally, a socio-economic and WASH practices survey was conducted in the communities. Free residual chlorine (FRC) and microbiological contamination were measured; at the borehole, treatment site, distribution points, and households's water containers. In Big Five, water was collected from unimproved sources before DWS construction. Despite that, only 16,6% of households used efficient water treatment methods, resulting in 73% of water stored unsafe for consumption. After construction, household water quality drastically improved, regardless of FRC fluctuations; 93% of samples were classified as low health risk (safe). The renovation guaranteed continuous supply through electro-chlorinators in RVA, where chlorination was intermittent. Water from DWS with adequate chlorine levels prevented microbiological contamination in households for 12 hours. Although economically attractive, the system's sustainability will require future evaluation.


Asunto(s)
Cloro , Purificación del Agua , Calidad del Agua , Abastecimiento de Agua , Abastecimiento de Agua/normas , Purificación del Agua/métodos , Cloro/análisis , República Democrática del Congo , Agua Potable/microbiología , Agua Potable/análisis , Agua Potable/química , Microbiología del Agua , Humanos , Halogenación
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