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Dípteros , Miasis , Humanos , Miasis/parasitología , Miasis/diagnóstico , Costa Rica , Animales , Masculino , Viaje , LarvaRESUMEN
The molecular detection of Toxoplasma gondii DNA is a key tool for the diagnosis of disseminated and congenital toxoplasmosis. This multicentric study from the Molecular Biology Pole of the French National Reference Center for toxoplasmosis aimed to evaluate Toxoplasma gondii Real-TM PCR kit (Sacace). The study compared the analytical and clinical performances of this PCR assay with the reference PCRs used in proficient laboratories. PCR efficiencies varied from 90% to 112%; linearity zone extended over four log units (R2 > 0.99) and limit of detection varied from 0.01 to ≤1 Tg/mL depending on the center. Determined on 173 cryopreserved DNAs from a large range of clinical specimens, clinical sensitivity was 100% [106/106; 95 confidence interval (CI): 96.5%-100%] and specificity was 100% (67/67; 95 CI: 94.6%-100%). The study revealed two potential limitations of the Sacace PCR assay: the first was the inconsistency of the internal control (IC) when added to the PCR mixture. This point was not found under routine conditions when the IC was added during the extraction step. The second is a lack of practicality, as the mixture is distributed over several vials, requiring numerous pipetting operations. Overall, this study provides useful information for the molecular diagnosis of toxoplasmosis; the analytical and clinical performances of the Sacace PCR kit were satisfactory, the kit having sensitivity and specificity similar to those of expert center methods and being able to detect low parasite loads, at levels where multiplicative analysis gives inconsistently positive results. Finally, the study recommends multiplicative analysis in particular for amniotic fluids, aqueous humor, and other single specimens.
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Toxoplasma , Toxoplasmosis Congénita , Toxoplasmosis , Humanos , Toxoplasma/genética , Toxoplasmosis/diagnóstico , Toxoplasmosis/parasitología , Toxoplasmosis Congénita/diagnóstico , Toxoplasmosis Congénita/parasitología , ADN , Juego de Reactivos para Diagnóstico , Sensibilidad y Especificidad , ADN Protozoario/genética , ADN Protozoario/análisisRESUMEN
Stiripentol (Diacomit®) (STP) is an orally active antiseizure medication (ASM) indicated as adjunctive therapy, for the treatment of seizures associated with Dravet syndrome (DS), a severe form of childhood epilepsy, in conjunction with clobazam and, in some regions valproic acid. Since the discovery of STP, several mechanisms of action (MoA) have been described that may explain its specific effect on seizures associated with DS. STP is mainly considered as a potentiator of gamma-aminobutyric acid (GABA) neurotransmission: (i) via uptake blockade, (ii) inhibition of degradation, but also (iii) as a positive allosteric modulator of GABAA receptors, especially those containing α3 and δ subunits. Blockade of voltage-gated sodium and T-type calcium channels, which is classically associated with anticonvulsant and neuroprotective properties, has also been demonstrated for STP. Finally, several studies indicate that STP could regulate glucose energy metabolism and inhibit lactate dehydrogenase. STP is also an inhibitor of several cytochrome P450 enzymes involved in the metabolism of other ASMs, contributing to boost their anticonvulsant efficacy as add-on therapy. These different MoAs involved in treatment of DS and recent data suggest a potential for STP to treat other neurological or non-neurological diseases.
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Dioxolanos , Epilepsias Mioclónicas , Humanos , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Dioxolanos/farmacología , Dioxolanos/uso terapéutico , Convulsiones/tratamiento farmacológico , Epilepsias Mioclónicas/tratamiento farmacológico , Ácido gamma-AminobutíricoRESUMEN
Malaria remains a global health problem, with 247 million cases and 619,000 deaths in 2021. Diagnosis of Plasmodium species is important for administering the appropriate treatment. The gold-standard diagnosis for accurate species identification remains the thin blood smear. Nevertheless, this method is time-consuming and requires highly skilled and trained microscopists. To overcome these issues, new diagnostic tools based on deep learning are emerging. This study aimed to evaluate the performances of a real-time detection transformer (RT-DETR) object detection algorithm to discriminate Plasmodium species on thin blood smear images. The algorithm was trained and validated on a data set consisting in 24,720 images from 475 thin blood smears corresponding to 2,002,597 labels. Performances were calculated with a test data set of 4,508 images from 170 smears corresponding to 358,825 labels coming from six French university hospitals. At the patient level, the RT-DETR algorithm exhibited an overall accuracy of 79.4% (135/170) with a recall of 74% (40/54) and 81.9% (95/116) for negative and positive smears, respectively. Among Plasmodium-positive smears, the global accuracy was 82.7% (91/110) with a recall of 90% (38/42), 81.8% (18/22), and 76.1% (35/46) for P. falciparum, P. malariae, and P. ovale/vivax, respectively. The RT-DETR model achieved a World Health Organization (WHO) competence level 2 for species identification. Besides, the RT-DETR algorithm may be run in real-time on low-cost devices such as a smartphone and could be suitable for deployment in low-resource setting areas lacking microscopy experts.IMPORTANCEMalaria remains a global health problem, with 247 million cases and 619,000 deaths in 2021. Diagnosis of Plasmodium species is important for administering the appropriate treatment. The gold-standard diagnosis for accurate species identification remains the thin blood smear. Nevertheless, this method is time-consuming and requires highly skilled and trained microscopists. To overcome these issues, new diagnostic tools based on deep learning are emerging. This study aimed to evaluate the performances of a real-time detection transformer (RT-DETR) object detection algorithm to discriminate Plasmodium species on thin blood smear images. Performances were calculated with a test data set of 4,508 images from 170 smears coming from six French university hospitals. The RT-DETR model achieved a World Health Organization (WHO) competence level 2 for species identification. Besides, the RT-DETR algorithm may be run in real-time on low-cost devices and could be suitable for deployment in low-resource setting areas.
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Malaria Falciparum , Malaria , Piperazinas , Plasmodium , Humanos , Algoritmos , Plasmodium falciparumRESUMEN
The size of body compartments is a determinant of several factors of blood viscosity. Red cell aggregation is proportional to fat mass while hematocrit is proportional to both fat-free mass and abdominal adiposity, but which parts of these body components are involved in this relationship is not known. Segmental bioelectrical impedance analysis (sBIA) provides a possibility to delineate the relationships more precisely between various subdivisions of the body and blood viscosity factors, going farther than preceding studies using non segmental BIA. In this study we investigated in 38 subjects undergoing a standardized breakfast test with mathematical modelling of glucose homeostasis and a segmental bioelectrical impedance analysis (sBIA) the relationships between the various compartments of the body and viscosity factors. Blood and plasma viscosity were measured with the Anton Paar rheometer and analyzed with Quemada's model. The parameters better correlated to hematocrit are fat free mass (râ=â0.562) and its two components muscle mass (râ=â0.516) and non-muscular fat-free mass (râ=â0.452), and also trunk fat mass (râ=â0.383) and waist-to hip ratio (râ=â0.394). Red cell aggregation measurements were correlated with both truncal and appendicular fat mass (r ranging between 0.603 and 0.728). Weaker correlations of M and M1 are found with waist circumference and hip circumference. This study shows that the correlation between lean mass and hematocrit involves both muscle and non-muscle moieties of lean mass, and that both central and appendicular fat are determinants of red cell aggregation.
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Viscosidad Sanguínea , Hemorreología , Humanos , Viscosidad Sanguínea/fisiología , Hemorreología/fisiología , Agregación Eritrocitaria/fisiología , Hematócrito , ViscosidadRESUMEN
INTRODUCTION: Alzheimer's Prevention Initiative Generation Study 1 evaluated amyloid beta (Aß) active immunotherapy (vaccine) CAD106 and BACE-1 inhibitor umibecestat in cognitively unimpaired 60- to 75-year-old participants at genetic risk for Alzheimer's disease (AD). The study was reduced in size and terminated early. Results from the CAD106 cohort are presented. METHODS: Sixty-five apolipoprotein E ε4 homozygotes with/without amyloid deposition received intramuscular CAD106 450 µg (n = 42) or placebo (n = 23) at baseline; Weeks 1, 7, 13; and quarterly; 51 of them had follow-up Aß positron emission tomography (PET) scans at 18 to 24 months. RESULTS: CAD106 induced measurable serum Aß immunoglobulin G titers in 41/42 participants, slower rates of Aß plaque accumulation (mean [standard deviation] annualized change from baseline in amyloid PET Centiloid: -0.91[5.65] for CAD106 versus 8.36 [6.68] for placebo; P < 0.001), and three amyloid-related imaging abnormality cases (one symptomatic). DISCUSSION: Despite early termination, these findings support the potential value of conducting larger prevention trials of Aß active immunotherapies in individuals at risk for AD. HIGHLIGHTS: This was the first amyloid-lowering prevention trial in persons at genetic risk of late-onset Alzheimer's disease (AD). Active immunotherapy targeting amyloid (CAD106) was tested in this prevention trial. CAD106 significantly slowed down amyloid plaque deposition in apolipoprotein E homozygotes. CAD106 was generally safe and well tolerated, with only three amyloid-related imaging abnormality cases (one symptomatic). Such an approach deserves further evaluation in larger AD prevention trials.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Humanos , Persona de Mediana Edad , Anciano , Péptidos beta-Amiloides/metabolismo , Enfermedad de Alzheimer/terapia , Enfermedad de Alzheimer/tratamiento farmacológico , Homocigoto , Apolipoproteína E4/genética , Placa Amiloide , Amiloide/metabolismo , Tomografía de Emisión de Positrones , Inmunoterapia , Encéfalo/metabolismoRESUMEN
Gold nanoparticles (AuNPs) are increasingly used for their thermoplasmonic properties, i.e., their ability to convert light energy into heat through plasmon resonance. However, measuring temperature gradients generated at the microscale by assemblies of AuNPs remains challenging, especially for random 3D distributions of AuNPs. Here, we introduce a label-free thermometry approach, combining quantitative wavefront microscopy and numerical simulations, to infer the heating power dissipated by a 3D model system consisting of emulsion microdroplets loaded with AuNPs. This approach gives access to the temperature reached in the droplets under laser irradiation without the need for extrinsic calibration. This versatile thermometry method is promising for noninvasive temperature measurements in various 3D microsystems involving AuNPs as colloidal heat sources, including photothermal drug delivery systems.
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Neurogenic heterotopic ossifications are intramuscular bone formations developing following central nervous system injury. The pathophysiology is poorly understood and current treatments for this debilitating condition remain unsatisfying. Here we explored the role of miRNAs in a clinically relevant mouse model that combines muscle and spinal cord injury, and in patients' cells. We found an osteo-suppressive miRNAs response in injured muscle that was hindered when the spinal cord injury was associated. In isolated fibro-adipogenic progenitors from damaged muscle (cells at the origin of ossification), spinal cord injury induced a downregulation of osteo-suppressive miRNAs while osteogenic markers were overexpressed. The overexpression of selected miRNAs in patient's fibro-adipogenic progenitors inhibited mineralization and osteo-chondrogenic markers in vitro. Altogether, we highlighted an osteo-suppressive mechanism involving multiple miRNAs in response to muscle injury that prevents osteogenic commitment which is ablated by the neurologic lesion in heterotopic ossification pathogenesis. This provides new research hypotheses for preventive treatments.
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MicroARNs , Osificación Heterotópica , Traumatismos de la Médula Espinal , Animales , Ratones , Traumatismos de la Médula Espinal/genética , Transducción de Señal , Osteogénesis/genética , MicroARNs/genética , Osificación Heterotópica/genéticaRESUMEN
The complexity of the water adsorption-desorption mechanism at the interface of transition metal dichalcogenides (TMDs) and its impact on their current transport are not yet fully understood. Here, our work investigates the swift intercalation of atmospheric adsorbates at the TMD and sapphire interface and between two TMD monolayers and probes its influence on their electrical properties. The adsorbates consist mainly of hydroxyl-based (OH) species in the subsurface region suggesting persistent water intercalation even under vacuum conditions, as determined by time-of-flight-secondary ion mass spectrometry (ToF-SIMS) and scanning tunneling microscopy (STM). Water intercalates there rapidly, within the order of a few minutes after being exposed to ambient atmosphere, this process tends to be partly reversible under (ultra)high vacuum, as observed by time-dependent scanning probe microscopy (SPM) based conductivity and ToF-SIMS measurements. A significant enhancement of the electronic properties is observed with the complete desorption of intercalated water clusters because of the pressure-induced melting effect under the tip of the SPM probe. Conversely, it also indicates that the characterization of TMD samples is substantially affected in air, in inert environments, and to some extent even in a vacuum if water intercalation is present. More importantly, STM analysis has uncovered a correlation between water intercalation and the presence of defects, showcasing their role in the gradual degradation of the material as it ages.
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Accurate tools for Toxoplasma gondii detection and quantification can be valuable for the early and effective management of toxoplasmosis. Droplet digital PCR (ddPCR) is a next-generation end-point PCR technique with high performance. The objective of the study was to evaluate the performance of ddPCR for the detection and absolute quantification of T. gondii. From January 2019 to October 2020, DNA samples collected at the Laboratory of Parasitology and Mycology of Pitié-Salpêtrière Hospital in Paris were retrospectively analyzed by ddPCR and real-time quantitative PCR (qPCR). To detect T. gondii with the best sensitivity possible, the REP-529 multicopy target was used. For absolute quantification of T. gondii, a specific single-copy target of α-tubulin was designed. T. gondii detection by ddPCR and qPCR was strongly correlated (R2 = 0.93), with a total concordance of 96.7% (n = 145/150). Quantification of T. gondii using ddPCR was successful for 15 of 35 samples showing a parasite load ≥170 copies/mL of DNA eluate using the α-tubulin target. The qPCR REP-529 quantification based on a standard curve was approximate and dependent on the strain genotype, which led to an estimate of parasite copy number 14- to 160-fold superior to the ddPCR result. In total, ddPCR is an effective molecular method for T. gondii detection that shows equivalent performance to qPCR. For robust T. gondii quantification, ddPCR is clearly more accurate than semiquantitative qPCR methods.
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Toxoplasma , Humanos , Estudios Retrospectivos , Toxoplasma/genética , Tubulina (Proteína)/genética , Sensibilidad y Especificidad , Reacción en Cadena en Tiempo Real de la Polimerasa/métodosRESUMEN
BACKGROUND: There is a critical need for novel primary endpoints designed to detect early and subtle changes in cognition in clinical trials targeting the asymptomatic (preclinical) phase of Alzheimer's disease (AD). The Alzheimer's Prevention Initiative (API) Generation Program, conducted in cognitively unimpaired individuals at risk of developing AD (e.g., enriched by the apolipoprotein E (APOE) genotype), used a novel dual primary endpoints approach, whereby demonstration of treatment effect in one of the two endpoints is sufficient for trial success. The two primary endpoints were (1) time to event (TTE)-with an event defined as a diagnosis of mild cognitive impairment (MCI) due to AD and/or dementia due to AD-and (2) change from baseline to month 60 in the API Preclinical Composite Cognitive (APCC) test score. METHODS: Historical observational data from three sources were used to fit models to describe the TTE and the longitudinal APCC decline, both in people who do and do not progress to MCI or dementia due to AD. Clinical endpoints were simulated based on the TTE and APCC models to assess the performance of the dual endpoints versus each of the two single endpoints, with the selected treatment effect ranging from a hazard ratio (HR) of 0.60 (40% risk reduction) to 1 (no effect). RESULTS: A Weibull model was selected for TTE, and power and linear models were selected to describe the APCC score for progressors and non-progressors, respectively. Derived effect sizes in terms of reduction of the APCC change from baseline to year 5 were low (0.186 for HR = 0.67). The power for the APCC alone was consistently lower compared to the power of TTE alone (58% [APCC] vs 84% [TTE] for HR = 0.67). Also, the overall power was higher for the 80%/20% distribution (82%) of the family-wise type 1 error rate (alpha) between TTE and APCC compared to 20%/80% (74%). CONCLUSIONS: Dual endpoints including TTE and a measure of cognitive decline perform better than the cognitive decline measure as a single primary endpoint in a cognitively unimpaired population at risk of AD (based on the APOE genotype). Clinical trials in this population, however, need to be large, include older age, and have a long follow-up period of at least 5 years to be able to detect treatment effects.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/prevención & control , Apolipoproteínas E/genética , Cognición , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/genética , Factores de RiesgoRESUMEN
BACKGROUND: Despite the availability of whole exome (WES) and genome sequencing (WGS), chromosomal microarray (CMA) remains the first-line diagnostic test in most rare disorders diagnostic workup, looking for copy number variations (CNVs), with a diagnostic yield of 10%-20%. The question of the equivalence of CMA and WES in CNV calling is an organisational and economic question, especially when ordering a WGS after a negative CMA and/or WES. METHODS: This study measures the equivalence between CMA and GATK4 exome sequencing depth of coverage method in detecting coding CNVs on a retrospective cohort of 615 unrelated individuals. A prospective detection of WES-CNV on a cohort of 2418 unrelated individuals, including the 615 individuals from the validation cohort, was performed. RESULTS: On the retrospective validation cohort, every CNV detectable by the method (ie, a CNV with at least one exon not in a dark zone) was accurately called (64/64 events). In the prospective cohort, 32 diagnoses were performed among the 2418 individuals with CNVs ranging from 704 bp to aneuploidy. An incidental finding was reported. The overall increase in diagnostic yield was of 1.7%, varying from 1.2% in individuals with multiple congenital anomalies to 1.9% in individuals with chronic kidney failure. CONCLUSION: Combining single-nucleotide variant (SNV) and CNV detection increases the suitability of exome sequencing as a first-tier diagnostic test for suspected rare Mendelian disorders. Before considering the prescription of a WGS after a negative WES, a careful reanalysis with updated CNV calling and SNV annotation should be considered.
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Variaciones en el Número de Copia de ADN , Exoma , Humanos , Variaciones en el Número de Copia de ADN/genética , Exoma/genética , Estudios Retrospectivos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Estudios ProspectivosRESUMEN
Marked by the killing of a senior ICT professional working for the Electoral Commission and the invalidation of the presidential election by the Supreme Court, the 2017 Kenyan elections make for a good case through which to study how digital technologies shape contemporary electoral practice. This article examines the practice of electoral transparency through technology and argues that it can be conceived as a socio-technical device based both on distancing people from knowledge of the electoral infrastructure and on staging a simplified discourse on public access to the electoral infrastructure. Drawing on interviews with key actors in election technology implementation and ethnographic observations of public events around it, the article argues that digital technology has had three sets of implications for elections. First, it has shaped the electoral infrastructure and the nature of the final result (now a paper and digital hybrid). Second, it has shaped the distribution of knowledge among electoral professionals, giving a central role to ICT actors, objects, and knowledge in the definition of electoral transparency. Third, the centrality of ICTs in elections and the order of knowledge they bring are highly controversial and criticized by other electoral actors who demand for material proof for understanding the inner workings of elections.
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Política , Humanos , KeniaRESUMEN
OBJECTIVE: To understand the impact of pediatric multiple sclerosis (MS), health-related quality of life (HRQL) measures have been used. However, specific areas of concern of youths with MS are not known. The objective of this study was to contribute content for inclusion in a new condition-specific measure of the life impact of MS for children and adolescents. METHODS: A patient engagement framework was used, and an online survey was developed using the Patient Generated Index (PGI). Text threads generated by the PGI were mapped to the International Classification of Functioning, Disability, and Health (ICF) and the Comprehensive ICF Core Set for MS. RESULTS: A total of 20 people completed the PGI survey of which 11 were youths with MS aged 14 to 22 years. Over 75% of the areas nominated by youths with MS were related to activities and participation and approximately 20% were related to body function. In contrast, 60% of the areas nominated by parents were related to body function. This finding indicated that a measure of life impact would need to include both impairments associated with MS and important activities and roles. This new approach has a disability component covers MS-related impairments and is completed using the PGI system where the youth select disability areas affected by MS, rate, and prioritize each area for improvement. The "quality of life" component queries those areas that are going well. CONCLUSION: This new measurement approach could prove useful in overcoming challenges in developing condition-specific measures for rare conditions.
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Personas con Discapacidad , Esclerosis Múltiple , Adolescente , Niño , Evaluación de la Discapacidad , Progresión de la Enfermedad , Humanos , Esclerosis Múltiple/diagnóstico , Calidad de Vida , Encuestas y CuestionariosRESUMEN
Formation of aqueous-core polymer capsules exhibiting an upper critical solution temperature (UCST) was achieved using surfactant-polymer interfacial complexation in water-in-oil inverse emulsions. In fluorinated oil, Coulombic interactions between Krytox, an anionic oil-soluble surfactant, and a cationic poly(lysine) grafted with poly(acrylamide-co-acrylonitrile) enabled the formation of an adsorbed polymer shell at the surface of water droplets. The thermoresponsiveness of the polymer shell was assessed by fluorescence microscopy with and without the presence of nanoparticles, including gold particles. We show that, above the cloud point, polymers with a balanced fraction of UCST grafts form flat adlayers that (i) spontaneously entrap nanoparticles upon cooling and (ii) switch from fluid-like dynamics at high temperature to solid-like dynamics below the cloud point. This system offers a straightforward mean to prepare temperature-sensitive capsules in mild, biocompatible conditions and to concentrate nanoparticles (including nanoheaters) in their shell.
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Polímeros , Agua , Cápsulas , Tensoactivos , TemperaturaRESUMEN
Real-time PCR plays a crucial role in the diagnosis of toxoplasmosis. In this multicenter study, the Toxoplasma RealCycler Universal assay was assessed for the diagnosis of toxoplasmosis by eight reference laboratories. DNAs from diverse clinical samples were included: 141 characterized samples from patients with different clinical forms of proven toxoplasmosis and 27 from patients without toxoplasmosis were tested in duplicate with the commercial assay. Final diagnosis was affirmed by each center by analysis of clinical settings and biological follow-up. Calibrated Toxoplasma gondii standards and 11 external quality control samples were also included. Discrepant results observed after the first run of commercial PCR were controlled by both reference and commercial PCR assays. Using the commercial assay, the detection threshold varied from 0.01 to 1 tachyzoites/mL, depending on the center. The relationship between crossing point and DNA concentration was linear over 4 log units (r2 > 0.99), and PCR efficiencies were satisfactory (89% to 104%). The results of the 11 external quality control samples were concordant after one retesting, but those for 3 clinical samples remained discrepant. Sensitivity and specificity were calculated at 97.8% (95% CI, 97.8%-100%) and 100% (95% CI, 87.2%-100%), respectively. Provided that PCRs are performed at least in duplicate to detect low parasitic loads, Toxoplasma RealCycler Universal PCR showed suitable performances to diagnose the different forms of toxoplasmosis.
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Toxoplasma , Toxoplasmosis , ADN Protozoario/análisis , ADN Protozoario/genética , Humanos , Técnicas de Amplificación de Ácido Nucleico/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa , Estándares de Referencia , Sensibilidad y Especificidad , Toxoplasma/genética , Toxoplasmosis/diagnóstico , Toxoplasmosis/parasitologíaRESUMEN
Recent literature shows that exercise is not simply a way to generate a calorie deficit as an add-on to restrictive diets but exerts powerful additional biological effects via its impact on mitochondrial function, the release of chemical messengers induced by muscular activity, and its ability to reverse epigenetic alterations. This review aims to summarize the current literature dealing with the hypothesis that some of these effects of exercise unexplained by an energy deficit are related to the balance of substrates used as fuel by the exercising muscle. This balance of substrates can be measured with reliable techniques, which provide information about metabolic disturbances associated with sedentarity and obesity, as well as adaptations of fuel metabolism in trained individuals. The exercise intensity that elicits maximal oxidation of lipids, termed LIPOXmax, FATOXmax, or FATmax, provides a marker of the mitochondrial ability to oxidize fatty acids and predicts how much fat will be oxidized over 45-60 min of low- to moderate-intensity training performed at the corresponding intensity. LIPOXmax is a reproducible parameter that can be modified by many physiological and lifestyle influences (exercise, diet, gender, age, hormones such as catecholamines, and the growth hormone-Insulin-like growth factor I axis). Individuals told to select an exercise intensity to maintain for 45 min or more spontaneously select a level close to this intensity. There is increasing evidence that training targeted at this level is efficient for reducing fat mass, sparing muscle mass, increasing the ability to oxidize lipids during exercise, lowering blood pressure and low-grade inflammation, improving insulin secretion and insulin sensitivity, reducing blood glucose and HbA1c in type 2 diabetes, and decreasing the circulating cholesterol level. Training protocols based on this concept are easy to implement and accept in very sedentary patients and have shown an unexpected efficacy over the long term. They also represent a useful add-on to bariatric surgery in order to maintain and improve its weight-lowering effect. Additional studies are required to confirm and more precisely analyze the determinants of LIPOXmax and the long-term effects of training at this level on body composition, metabolism, and health.
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Diabetes Mellitus Tipo 2 , Tejido Adiposo/metabolismo , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Ejercicio Físico/fisiología , Humanos , Lípidos , Oxidación-Reducción , Consumo de OxígenoRESUMEN
PURPOSE: To evaluate emotional distress and prenatal attachment throughout a subsequent pregnancy after Termination of Pregnancy (TOP) for fetal abnormality. METHODS: Observational study, in a French Tertiary Maternity. POPULATION: 25 women in a subsequent pregnancy after a medical termination of pregnancy for foetal abnormality, 18-year-old and older. Prenatal Interviews at 20 Gestationnal weeks (GW), 27 GW and 35 GW and Postnatal at 3 months and at each time self-administered questionnaires of anxiety, post-traumatic stress syndrome (PCLS) depressive symptoms (EPDS), prenatal attachment (PAI) and Perinatal Grief Scale (PGS). RESULTS: Pregnancy onset, i.e. before 20 GW, showed increased prevalence of anxiety (16/23, 66.7%), depression (7/23, 30.4%) and post-traumatic stress symptoms (4/16, 25%). Total score on PGS is higher in onset of pregnancy than in the third trimester (p = 0.005). Prenatal attachment was lower during early pregnancy (p = 0.003) and correlated inversely with grief intensity (p = 0.022). During late pregnancy, emotional symptoms decrease, and prenatal attachment stopped increase positively, specifically among women whose foetal abnormality in previous pregnancies were diagnosed late, at an average of 25 GW. CONCLUSION: This research shows the specific dynamics of pregnancies following TOP and highlights the necessity for early prenatal psychological support. One should also pay special attention to prenatal attachment during late pregnancy even after knowing that the fetus is healthy.
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Ansiedad , Pesar , Aborto Eugénico/psicología , Adolescente , Adulto , Ansiedad/epidemiología , Ansiedad/psicología , Familia , Femenino , Feto/anomalías , Humanos , Embarazo/psicología , Tercer Trimestre del Embarazo , Encuestas y CuestionariosRESUMEN
The cells of origin of neurogenic heterotopic ossifications (NHOs), which develop frequently in the periarticular muscles following spinal cord injuries (SCIs) and traumatic brain injuries, remain unclear because skeletal muscle harbors two progenitor cell populations: satellite cells (SCs), which are myogenic, and fibroadipogenic progenitors (FAPs), which are mesenchymal. Lineage-tracing experiments using the Cre recombinase/LoxP system were performed in two mouse strains with the fluorescent protein ZsGreen specifically expressed in either SCs or FAPs in skeletal muscles under the control of the Pax7 or Prrx1 gene promoter, respectively. These experiments demonstrate that following muscle injury, SCI causes the upregulation of PDGFRα expression on FAPs but not SCs and the failure of SCs to regenerate myofibers in the injured muscle, with reduced apoptosis and continued proliferation of muscle resident FAPs enabling their osteogenic differentiation into NHOs. No cells expressing ZsGreen under the Prrx1 promoter were detected in the blood after injury, suggesting that the cells of origin of NHOs are locally derived from the injured muscle. We validated these findings using human NHO biopsies. PDGFRα+ mesenchymal cells isolated from the muscle surrounding NHO biopsies could develop ectopic human bones when transplanted into immunocompromised mice, whereas CD56+ myogenic cells had a much lower potential. Therefore, NHO is a pathology of the injured muscle in which SCI reprograms FAPs to undergo uncontrolled proliferation and differentiation into osteoblasts.
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Assessment of age-dependent cancer risk for carriers of a predicted pathogenic variant (PPV) is often hampered by biases in data collection, with a frequent under-representation of cancer-free PPV carriers. TUMOSPEC was designed to estimate the cumulative risk of cancer for carriers of a PPV in a gene that is usually tested in a hereditary breast and ovarian cancer context. Index cases are enrolled consecutively among patients who undergo genetic testing as part of their care plan in France. First- and second-degree relatives and cousins of PPV carriers are invited to participate whether they are affected by cancer or not, and genotyped for the familial PPV. Clinical, family and epidemiological data are collected, and all data including sequencing data are centralized at the coordinating centre. The three-year feasibility study included 4431 prospective index cases, with 19.1% of them carrying a PPV. When invited by the coordinating centre, 65.3% of the relatives of index cases (5.7 relatives per family, on average) accepted the invitation to participate. The study logistics were well adapted to clinical and laboratory constraints, and collaboration between partners (clinicians, biologists, coordinating centre and participants) was smooth. Hence, TUMOSPEC is being pursued, with the aim of optimizing clinical management guidelines specific to each gene.