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1.
Pediatr Allergy Immunol ; 35(5): e14146, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38783409

RESUMO

BACKGROUND: Oral immunotherapy (OIT) is an increasingly acceptable therapeutic option for peanut-allergic (PA) children, despite significant side effects. Major peanut allergenic proteins are heat-resistant and are not rendered hypoallergenic after baking or cooking. Lyophilized peanut protein-MH (LPP-MH) is a novel composition from developing peanuts, enabling cooking-induced reduction in allergenicity. We aimed to explore the safety and efficacy of OIT, with extensively heated and baked (EHEB) LPP-MH in PA children. METHODS: In a single-arm, single-center, pilot study, PA children with a single highest tolerated dose of <100 mg peanut protein were placed on a 40-week OIT protocol with 300 mg daily of heat-treated LPP-MH. A repeat open peanut food challenge was performed after 40 weeks of treatment and at a 6-12 months of follow-up visit. RESULTS: Thirty-three children with PA were enrolled, with a mean cumulative tolerated dose (MCTD) of 71.2 mg PP (95% CI 45-100 mg). After 40 weeks, 32/33 patients were able to consume more than 300 mg of natural PP, with MCTD of 1709 mg (CI 365-3675 mg). There were no severe allergic reactions requiring epinephrine, during any of the observed LPP-MH challenges or any treatment related doses at home. After 6-12 months on daily maintenance, the MCTD was 8821 mg (95% CI 1930-13,500 mg). This enabled most children age-appropriate dietary inclusion of peanuts. CONCLUSION: An OIT protocol with heat-treated LPP-MH, a novel composition from developing peanuts, seems a potentially safe and efficacious OIT modality for PA children, enabling the introduction of dietary levels of peanut proteins in highly allergic PA children. Validation in randomized controlled studies is mandated.


Assuntos
Alérgenos , Arachis , Culinária , Dessensibilização Imunológica , Hipersensibilidade a Amendoim , Humanos , Hipersensibilidade a Amendoim/terapia , Hipersensibilidade a Amendoim/imunologia , Arachis/imunologia , Dessensibilização Imunológica/métodos , Masculino , Criança , Feminino , Administração Oral , Projetos Piloto , Alérgenos/imunologia , Alérgenos/administração & dosagem , Pré-Escolar , Temperatura Alta , Resultado do Tratamento , Adolescente , Proteínas de Plantas/imunologia , Proteínas de Plantas/administração & dosagem
2.
Artif Organs ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647271

RESUMO

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is widely used for children treated for refractory respiratory failures or refractory cardiogenic shock. Its duration depends on organ functions recovery. Weaning is decided using macro-circulatory tools, but microcirculation is not well evaluated. Sidestream dark-field video imaging is used to assess the perfusion of the sublingual microvascular vessels. The aim of this study was to assess the predictive value of microcirculatory indices in ECMO weaning. METHODS: This prospective monocentric study examined pediatric patients at Trousseau Hospital between March 2017 and December 2020. The study included all patients from 35 weeks of gestational age to 18 years old who were treated with ECMO. Children were divided into two groups: one with stability after weaning and the other with instability after weaning. We collected clinical and biological data, ventilation parameters, extracorporeal membrane oxygenation parameters, and drugs used at admission and after the weaning test. Microcirculations videos were taken after weaning trials with echocardiography and blood gas monitoring. RESULTS: The study included 30 patients with a median age of 29 days (range: 1-770 days) at admission, including 18 patients who received venoarterial ECMO (60%). There were 19 children in the stability group and 11 in the instability group. Macrocirculatory and microcirculatory indices showed no differences between groups. The microvascular flow index was subnormal in both groups (2.3 (1.8-2.4) and 2.3 (2.3-2.6), respectively; p = 0.24). The microvascular indices were similar between cases of venovenous and venoarterial ECMO and between age groups. CONCLUSION: Microcirculation monitoring at the weaning phase did not predict the failure of ECMO weaning.

3.
J Trauma Dissociation ; 25(3): 394-407, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38376101

RESUMO

Gender differences in the prevalence, types and outcomes of traumas have consistently been reported in the literature. Other research has documented that exposure to trauma is associated with the development and maintenance of pathological personality traits. In the current study, we examined the moderating role of gender in the association between lifetime exposure to trauma and pathological personality traits. The sample included 148 clients who sought treatment at a community mental health clinic. All participants completed online questionnaires including demographic information, the Trauma History Questionnaire (THQ), and the Personality Inventory for DSM-5-Brief Form (PID-5-BF) at the entry to treatment. Our findings documented a significant association between exposure to trauma and pathological personality traits in men, but not in women. Furthermore, this pattern of results was specifically evident within two personality domains: antagonism and detachment. These findings contribute to the theoretical understanding of the interplay between trauma, gender, and the development of pathological personality traits. They expand upon the growing knowledge about the mental health crisis among boys and men by shedding light on the unique vulnerabilities that men face in response to traumatic experiences and how these experiences can have a lasting impact on their adaptive functioning. Consequently, at the clinical level, the current study emphasizes the importance of paying particular attention to men's trauma histories and explicitly exploring these during the intake session.


Assuntos
Transtornos da Personalidade , Personalidade , Masculino , Humanos , Feminino , Fatores Sexuais , Transtornos da Personalidade/psicologia , Inventário de Personalidade , Inquéritos e Questionários , Manual Diagnóstico e Estatístico de Transtornos Mentais
4.
Eur Radiol ; 33(10): 7168-7177, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37086288

RESUMO

OBJECTIVES: Current surgical policy recommends comprehensive excision of tumorous calcifications in breast cancer patients following neoadjuvant chemotherapy (NAC) regardless of MRI outcomes, despite MRI defining tumor response superior to mammography. The current study examines MRI prediction of response in tumors with vs without calcifications, using post-NAC surgical pathology as the standard of reference. METHODS: Retrospective analysis of 114 NAC patients between 2011 and 2018 including demographics, mammography, 3 T-MRI, and pathology compared two sub-groups: without (n = 62) or with (n = 52) mammographic calcifications. In the calcification cohort, the mammographic extent of calcifications and MRI enhancement overlapped. MRI prediction of response to NAC was correlated with pathology. Two-tailed paired T and Fisher's exact tests and Cohen's kappa coefficient were applied for analysis. RESULTS: There was no significant difference between the two sub-groups regarding demographics. Tumors demonstrated equivalent features regarding size, lymph node involvement, and DCIS component. ER-negative/HER2-positive tumors more commonly exhibited calcifications (33% n = 17 calcified vs 13% n = 8 non-calcified; p < 0.05); triple negative pathology rarely calcified (6% n = 3 calcified vs 33% n = 20 non-calcified; p < 0.05). NME was more common with calcifications (62% n = 32 calcified vs 29% n = 18 non-calcified; p < 0.05) and mass enhancement without (90% n = 56 non-calcified vs 81% n = 42 calcified; p < 0.05). Both groups responded similarly to NAC (pCR = 37% non-calcified vs 38% calcified); response on MRI equally correlated with pathology (69% both subgroups; p = 0.988). CONCLUSION: We propose utilizing post-NAC MRI findings rather than mammography in planning surgery, as MRI prediction is independent of the presence or absence of calcifications. Prospective studies to evaluate this approach are warranted. KEY POINTS: • No difference was found in demographic, clinical, pathology, or imaging characteristics between patients with or without tumoral calcifications on mammography prior to neoadjuvant chemotherapy. • Residual mammographic calcifications are inadequate predictors of residual invasive disease. MRI accurately recognized complete response and correctly correlated with post-treatment surgical pathology in 69% of patients, regardless of the presence or absence of mammographic calcifications. • We propose utilizing post-NAC MRI findings rather than mammography in planning post-NAC surgery, as MRI prediction of response is independent of the presence or absence of calcifications.


Assuntos
Neoplasias da Mama , Calcinose , Humanos , Feminino , Terapia Neoadjuvante/métodos , Estudos Retrospectivos , Estudos Prospectivos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Mamografia/métodos , Calcinose/diagnóstico por imagem , Calcinose/patologia , Imageamento por Ressonância Magnética/métodos , Neoplasia Residual/patologia , Quimioterapia Adjuvante
5.
Theor Appl Genet ; 135(5): 1767-1777, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35260930

RESUMO

KEY MESSAGE: A major gene controls flowering pattern in peanut, possibly encoding a TFL1-like. It was subjected to gain/loss events of a deletion and changes in mRNA expression levels, partly explaining the evolution of flowering pattern in Arachis. Flowering pattern (FP) is a major characteristic differentiating the two subspecies of cultivated peanut (Arachis hypogaea L.). Subsp. fastigiata possessing flowers on the mainstem (MSF) and a sequential FP, whereas subsp. hypogaea lacks MSF and exhibits an alternate FP. FP is considered the main contributor to plant adaptability, and evidence indicates that its diversification occurred during the several thousand years of domestication. However, the genetic mechanism that controls FP in peanut is unknown. We investigated the genetics of FP in a recombinant inbred population, derivatives of an A. hypogaea by A. fastigiata cross. Lines segregated 1:1 for FP, indicating a single gene effect. Using Axiom_Arachis2 SNP-array, FP was mapped to a small segment in chromosome B02, wherein a Terminal Flowering 1-like (AhTFL1) gene with a 1492 bp deletion was found in the fastigiata line, leading to a truncated protein. Remapping FP in the RIL population with the AhTFL1 indel as a marker increased the LOD score from 53.3 to 158.8 with no recombination in the RIL population. The same indel was found co-segregating with the phenotype in two independent EMS-mutagenized M2 families, suggesting a hotspot for gene conversion. Also, AhTFL1 was significantly less expressed in the fastigiata line compared to hypogaea and in flowering than non-flowering branches. Sequence analysis of the AhTFL1 in peanut world collections indicated significant conservation, supporting the putative role of AhTFL1 in peanut speciation during domestication and modern cultivation.


Assuntos
Arachis , Arachis/genética , Genoma de Planta , Mutação INDEL , Fenótipo
6.
Acta Paediatr ; 111(5): 971-978, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35138655

RESUMO

AIM: Neonatologist-performed echocardiography (NPE) is recommended during shock. We aimed to assess factors associated with NPE utilisation in the NICU and physiological information obtained during management of shock. METHODS: An Internet-based survey, sent to neonatologists with interest in haemodynamics, studying NPE utilisation in shock management through a real clinical case and correlating its use with responders' training and NICU settings. RESULTS: Fifty-nine completed surveys were received from the United Kingdom: 38%, Western Europe: 32%, Canada: 23% and other countries: 7%. Whilst managing the given clinical case, 90% of responders expected first NPE to exclude congenital heart disease-although only 61% could exclude it confidently (71% in trained clinicians vs. 29% without training; p < 0.01). NPE utilisation prior to initiate treatment was significantly correlated with mean number of neonatologists able to perform NPE in the NICU (4.9 vs. 2.9 neonatologists per unit; p = 0.02). Similarly, for ongoing therapeutic guidance, NPE was more used in trained clinicians (p < 0.01). 88% and 81% of responders studied a combination of multiple parameters to assess filling and systemic flow, respectively. CONCLUSION: Neonatologist-performed echocardiography during shock management differs with previous training and number of doctors able to perform echocardiography in NICU. This study highlighted the need for enhanced training implementation.


Assuntos
Cardiopatias Congênitas , Neonatologia , Ecocardiografia , Hemodinâmica , Humanos , Neonatologistas , Neonatologia/educação , Inquéritos e Questionários
7.
Indian J Crit Care Med ; 26(6): 745-747, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35836619

RESUMO

Background: Human metapneumovirus (hMPV) is a paramyxovirus, well known as a causative agent of respiratory tract infections. Non-respiratory manifestations, including cardiac impairments, remain rare. Only two cases of myocarditis caused by hMPV have been described in adults. Case description: We present the case of a 14-year-old female suffering from Burkitt leukemia and diagnosed with severe myocarditis caused by hMPV, based on results from real-time polymerase chain reaction (RT-PCR) and magnetic resonance imaging (MRI). She was successfully treated by venoarterial extracorporeal membrane oxygenation and intravenous immunoglobulins. She was discharged from pediatric intensive care unit (PICU) 3 weeks later. Conclusion: This is the first pediatric case of hMPV myocarditis requiring venoarterial extracorporeal membrane oxygenation. How to cite this article: Makhlouf A, Peipoch L, Duport P, Darrieux E, Reguerre Y, Ramful D, et al. First Case of Acute Myocarditis Caused by Metapneumovirus in an Immunocompromised 14-year-old Girl. Indian J Crit Care Med 2022;26(6):745-747.

8.
BMC Plant Biol ; 21(1): 186, 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33874903

RESUMO

BACKGROUND: Time-to-maturation (TTM) is an important trait contributing to adaptability, yield and quality in peanut (Arachis hypogaea L). Virginia market-type peanut belongs to the late-maturing A. hypogaea subspecies with considerable variation in TTM within this market type. Consequently, planting and harvesting schedule of peanut cultivars, including Virginia market-type, need to be optimized to maximize yield and grade. Little is known regarding the genetic control of TTM in peanut due to the challenge of phenotyping and limited DNA polymorphism. Here, we investigated the genetic control of TTM within the Virginia market-type peanut using a SNP-based high-density genetic map. A recombinant inbred line (RIL) population, derived from a cross between two Virginia-type cultivars 'Hanoch' and 'Harari' with contrasting TTM (12-15 days on multi-years observations), was phenotyped in the field for 2 years following a randomized complete block design. TTM was estimated by maturity index (MI). Other agronomic traits like harvest index (HI), branching habit (BH) and shelling percentage (SP) were recorded as well. RESULTS: MI was highly segregated in the population, with 13.3-70.9% and 28.4-80.2% in years 2018 and 2019. The constructed genetic map included 1833 SNP markers distributed on 24 linkage groups, covering a total map distance of 1773.5 cM corresponding to 20 chromosomes on the tetraploid peanut genome with 1.6 cM mean distance between the adjacent markers. Thirty QTL were identified for all measured traits. Among the four QTL regions for MI, two consistent QTL regions (qMIA04a,b and qMIB03a,b) were identified on chromosomes A04 (118680323-125,599,371; 6.9Mbp) and B03 (2839591-4,674,238; 1.8Mbp), with LOD values of 5.33-6.45 and 5-5.35 which explained phenotypic variation of 9.9-11.9% and 9.3-9.9%, respectively. QTL for HI were found to share the same loci as MI on chromosomes B03, B05, and B06, demonstrating the possible pleiotropic effect of HI on TTM. Significant but smaller effects on MI were detected for BH, pod yield and SP. CONCLUSIONS: This study identified consistent QTL regions conditioning TTM for Virginia market-type peanut. The information and materials generated here can be used to further develop molecular markers to select peanut idiotypes suitable for diverse growth environments.


Assuntos
Arachis/crescimento & desenvolvimento , Arachis/genética , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas/fisiologia , Ligação Genética , Fenótipo
9.
BMC Plant Biol ; 21(1): 509, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732143

RESUMO

BACKGROUND: Peanut (Arachis hypogaea L.) belongs to an exceptional group of legume plants, wherein the flowers are produced aerially, but the pods develop under the ground. In such a unique environment, the pod's outer shell plays a vital role as a barrier against mechanical damage and soilborne pathogens. Recent studies have reported the uniqueness and importance of gene expression patterns that accompany peanut pods' biogenesis. These studies focused on biogenesis and pod development during the early stages, but the late developmental stages and disease resistance aspects still have gaps. To extend this information, we analyzed the transcriptome generated from four pod developmental stages of two genotypes, Hanoch (Virginia-type) and IGC53 (Peruvian-type), which differs significantly in their pod shell characteristics and pathogen resistance. RESULTS: The transcriptome study revealed a significant reprogramming of the number and nature of differentially expressed (DE) genes during shell development. Generally, the numbers of DE genes were higher in IGC53 than in Hanoch, and the R5-R6 transition was the most dynamic in terms of transcriptomic changes. Genes related to cell wall biosynthesis, modification and transcription factors (TFs) dominated these changes therefore, we focused on their differential, temporal and spatial expression patterns. Analysis of the cellulose synthase superfamily identified specific Cellulose synthase (CesAs) and Cellulose synthase-like (Csl) genes and their coordinated interplay with other cell wall-related genes during the peanut shell development was demonstrated. TFs were also identified as being involved in the shell development process, and their pattern of expression differed in the two peanut genotypes. The shell component analysis showed that overall crude fiber, cellulose, lignin, hemicelluloses and dry matter increased with shell development, whereas K, N, protein, and ash content decreased. Genotype IGC53 contained a higher level of crude fiber, cellulose, NDF, ADF, K, ash, and dry matter percentage, while Hanoch had higher protein and nitrogen content. CONCLUSIONS: The comparative transcriptome analysis identified differentially expressed genes, enriched processes, and molecular processes like cell wall biosynthesis/modifications, carbohydrate metabolic process, signaling, transcription factors, transport, stress, and lignin biosynthesis during the peanut shell development between two contrasting genotypes. TFs and other genes like chitinases were also enriched in peanut shells known for pathogen resistance against soilborne major pathogens causing pod wart disease and pod damages. This study will shed new light on the biological processes involved with underground pod development in an important legume crop.


Assuntos
Arachis/metabolismo , Proteínas de Plantas/metabolismo , Transcriptoma/genética , Arachis/genética , Parede Celular/metabolismo , Flores/genética , Flores/metabolismo , Regulação da Expressão Gênica de Plantas , Glucosiltransferases/genética , Glucosiltransferases/metabolismo , Proteínas de Plantas/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
10.
Crit Care ; 25(1): 369, 2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34774087

RESUMO

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (E-CPR) is used for the treatment of refractory cardiac arrest. However, the optimal target to reach for mean arterial pressure (MAP) remains to be determined. We hypothesized that MAP levels critically modify cerebral hemodynamics during E-CPR and tested two distinct targets (65-75 vs 80-90 mmHg) in a porcine model. METHODS: Pigs were submitted to 15 min of untreated ventricular fibrillation followed by 30 min of E-CPR. Defibrillations were then delivered until return of spontaneous circulation (ROSC). Extracorporeal circulation was initially set to an average flow of 40 ml/kg/min. The dose of epinephrine was set to reach a standard or a high MAP target level (65-75 vs 80-90 mmHg, respectively). Animals were followed during 120-min after ROSC. RESULTS: Six animals were included in both groups. During E-CPR, high MAP improved carotid blood flow as compared to standard MAP. After ROSC, this was conversely decreased in high versus standard MAP, while intra-cranial pressure was superior. The pressure reactivity index (PRx), which is the correlation coefficient between arterial blood pressure and intracranial pressure, also demonstrated inverted patterns of alteration according to MAP levels during E-CPR and after ROSC. In standard-MAP, PRx was transiently positive during E-CPR before returning to negative values after ROSC, demonstrating a reversible alteration of cerebral autoregulation during E-CPR. In high-MAP, PRx was negative during E-CPR but became sustainably positive after ROSC, demonstrating a prolonged alteration in cerebral autoregulation after ROSC. It was associated with a significant decrease in cerebral oxygen consumption in high- versus standard-MAP after ROSC. CONCLUSIONS: During early E-CPR, MAP target above 80 mmHg is associated with higher carotid blood flow and improved cerebral autoregulation. This pattern is inverted after ROSC with a better hemodynamic status with standard versus high-MAP.


Assuntos
Pressão Arterial , Reanimação Cardiopulmonar , Circulação Cerebrovascular , Oxigenação por Membrana Extracorpórea , Animais , Pressão Arterial/fisiologia , Reanimação Cardiopulmonar/métodos , Circulação Cerebrovascular/fisiologia , Hemodinâmica , Suínos , Resultado do Tratamento
11.
Acta Paediatr ; 110(3): 922-932, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33190340

RESUMO

AIM: This study determined the influence of the COVID-19 pandemic on the occurrence of multisystem inflammatory syndrome in children (MIS-C) and compared the main characteristics of MIS-C and Kawasaki disease (KD). METHODS: We included patients aged up to 18 years of age who were diagnosed with MIS-C or KD in a paediatric university hospital in Paris from 1 January 2018 to 15 July 2020. Clinical, laboratory and imaging characteristics were compared, and new French COVID-19 cases were correlated with MIS-C cases in our hospital. RESULTS: There were seven children with MIS-C, from 6 months to 12 years of age, who were all positive for the virus that causes COVID-19, and 40 virus-negative children with KD. Their respective characteristics were as follows: under 5 years of age (14.3% vs. 85.0%), paediatric intensive care unit admission (100% vs. 10.0%), abdominal pain (71.4% vs. 12.5%), myocardial dysfunction (85.7% vs. 5.0%), shock syndrome (85.7% vs. 2.5%) and mean and standard deviation C-reactive protein (339 ± 131 vs. 153 ± 87). There was a strong lagged correlation between the rise and fall in MIS-C patients and COVID-19 cases. CONCLUSION: The rise and fall of COVID-19 first wave mirrored the MIS-C cases. There were important differences between MIS-C and KD.


Assuntos
COVID-19/epidemiologia , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Adolescente , COVID-19/diagnóstico , COVID-19/terapia , Criança , Pré-Escolar , Feminino , França/epidemiologia , Hospitalização , Hospitais Pediátricos , Hospitais Universitários , Humanos , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Estudos Retrospectivos , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/terapia
12.
Radiology ; 297(3): E283-E288, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32515676

RESUMO

This case series examines cardiac MRI findings in four children and adolescents admitted to intensive care in April 2020 for multisystem inflammatory syndrome and Kawasaki disease-like features related to coronavirus disease 2019 (COVID-19). Acute myocarditis occurred less than 1 week after onset of fever and gastrointestinal symptoms. Physical examination showed rash and cheilitis or conjunctivitis. All patients recovered after intravenous immunoglobulin therapy. Severe acute respiratory syndrome coronavirus 2 reverse transcription polymerase chain reaction was negative in nasopharyngeal, stool, and respiratory samples and was positive on serology. Cardiac MRI showed diffuse myocardial edema on T2 short tau inversion-recovery sequences and native T1 mapping, with no evidence of late gadolinium enhancement suggestive of replacement fibrosis or focal necrosis. These findings favor postinfectious myocarditis in children and adolescents with COVID-19.


Assuntos
Infecções por Coronavirus/complicações , Imageamento por Ressonância Magnética/métodos , Pneumonia Viral/complicações , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico por imagem , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Betacoronavirus , COVID-19 , Criança , Feminino , Coração/diagnóstico por imagem , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Miocardite/diagnóstico por imagem , Miocardite/etiologia , Miocardite/terapia , Pandemias , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica/terapia , Resultado do Tratamento
13.
NMR Biomed ; 33(2): e4189, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31793111

RESUMO

Investigation of hyperpolarized substrate metabolism has been showing utility in real-time determination of in-cell and in vivo enzymatic activities. Intracellular reaction rates may vary during the course of a measurement, even on the very short time scales of visibility on hyperpolarized MR, due to many factors such as the availability of the substrate and co-factors in the intracellular space. Despite this potential variation, the kinetic analysis of hyperpolarized signals typically assumes that the same rate constant (and in many cases, the same rate) applies throughout the course of the reaction as observed via the build-up and decay of the hyperpolarized signals. We demonstrate here an acquisition approach that can null the need for such an assumption and enable the detection of instantaneous changes in the rate of the reaction during an ex vivo hyperpolarized investigation, (i.e. in the course of the decay of one hyperpolarized substrate dose administered to a viable tissue sample ex vivo). This approach utilizes hyperpolarized product selective saturating-excitation pulses. Similar pulses have been previously utilized in vivo for spectroscopic imaging. However, we show here favorable consequences to kinetic rate determinations in the preparations used. We implement this acquisition strategy for studies on perfused tissue slices and develop a theory that explains why this particular approach enables the determination of changes in enzymatic rates that are monitored via the chemical conversions of hyperpolarized substrates. Real-time changes in intracellular reaction rates are demonstrated in perfused brain, liver, and xenograft breast cancer tissue slices and provide another potential differentiation parameter for tissue characterization.


Assuntos
Sistemas Computacionais , Metabolismo , Animais , Simulação por Computador , Feminino , Humanos , Fígado/diagnóstico por imagem , Células MCF-7 , Camundongos SCID , Processamento de Sinais Assistido por Computador , Fatores de Tempo
14.
Pediatr Dermatol ; 37(6): 1051-1054, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32951239

RESUMO

BACKGROUND: Chronic urticaria is defined by the presence of itchy wheals, sometimes accompanied by angioedema, lasting for at least 6 weeks. In children, most cases occur without an eliciting factor and are defined as chronic spontaneous urticaria (CSU). CSU affects up to 0.75% of children with a negative impact on quality of life and school performance. CSU is treated in adults with second-generation antihistamines, increased up to four times normal doses for second-line treatment. Omalizumab (a monoclonal antibody to IgE) may be recommended as third-line therapy. A similar protocol is used in children, yet little is known of its efficacy and safety. OBJECTIVES: To summarize our multi-center experience in treating children with recalcitrant CSU with omalizumab. METHODS: A retrospective multi-center case series conducted in 5 tertiary care centers in Israel. Patients included were children <18 years old diagnosed with recalcitrant CSU who were treated with omalizumab. Patients were followed up throughout the duration of omalizumab therapy/symptom remission. Patients' electronic medical records were used to gather data. RESULTS: Nineteen participants (11 F; 8 M) presented with CSU between ages 6 and 16.9 years. Sixteen (84%) responded to omalizumab, including children <12 years old, although two became non-responsive after 6-12 months of therapy. Another three patients (16%) were resistant to treatment, achieving remission through fourth-line (Cyclosporine A) or other therapies. CONCLUSION: Children with recalcitrant CSU, even those <12 years old, respond well to standard-dose, third-line omalizumab therapy at rates similar to adults. Yet, some cases may become non-responsive with ongoing treatment.


Assuntos
Antialérgicos , Urticária Crônica , Urticária , Adolescente , Adulto , Antialérgicos/uso terapêutico , Criança , Doença Crônica , Humanos , Israel , Omalizumab/uso terapêutico , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento , Urticária/tratamento farmacológico
15.
Harm Reduct J ; 17(1): 55, 2020 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-32778108

RESUMO

BACKGROUND: After the collapse of the Soviet Union at the beginning of the 1990s, people who inject drugs spiked in Eastern Europe. Facing local repression and an array of factors encouraging emigration, some users have migrated to France. This population now make up to a third of the patient list of some harm reduction services in Paris. This article aims to present original data on the sociodemographic profiles of these users, on their migration trajectory, their life conditions, and on the evolution of their drug use practices since arriving in Paris. METHODS: Data were collected as part of the ANRS-Coquelicot Survey, an HIV and HCV seroprevalence study among French-speaking people who use drugs. A sub-sample of Russian-speaking drug users who had relocated from Eastern Europe to live in Paris completed a quantitative questionnaire (N = 150) and a qualitative semi-structured interview (N = 20). The survey aimed to describe participants' backgrounds, and a thematic analysis of interviews was conducted to explore participants' migration histories, their life conditions in Paris, and their drug use practices before and after arriving in France. RESULTS: This study highlights the great vulnerability of the participating population, often following a loss of social status after migrating to France. Another important finding is that participants had better access to harm reduction tools and reduced their risk of exposure to HIV and HCV infections linked to needle sharing. Although 60% said they had already shared a syringe in their lifetime (49.9% of them in their home country), the proportions shrank to 13.9% after they arrived in France and to 9.3% in the month before the study, a proportion that is lower than among French-speaking people who use drugs. CONCLUSIONS: Our main findings on the profiles and behaviors of the study population lead us to make two recommendations: to offer stronger global care to these users in Paris and to reform drug policy in their home countries by integrating it into a public health approach.


Assuntos
Usuários de Drogas/estatística & dados numéricos , Emigração e Imigração/estatística & dados numéricos , Redução do Dano , Acontecimentos que Mudam a Vida , Programas de Troca de Agulhas , Abuso de Substâncias por Via Intravenosa/epidemiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paris/epidemiologia , Fatores Socioeconômicos , Abuso de Substâncias por Via Intravenosa/terapia , Inquéritos e Questionários , U.R.S.S./etnologia , Populações Vulneráveis/estatística & dados numéricos
16.
Sante Publique ; Vol. 32(1): 43-55, 2020 Jun 18.
Artigo em Francês | MEDLINE | ID: mdl-32706225

RESUMO

INTRODUCTION: According to the French National Institute of Health and Medical Research (INSERM), 12% of children and youth living in France (one in eight) suffer from mental disorders. However, the conditions for this population to use mental health services remain poorly explored.Purpose of research: Our aim was to provide a double-statistical and discursive-perspective on the orientation of this population towards public child psychiatry centers (socio-demographic profile, actors who made the requests, reasons for first consultations, difficulties and disorders qualification by parents…). METHODS: This article is based on a quantitative and qualitative survey conducted in 6 public health centers in Paris: two Medical-Psychological Centers (CMP), two Medico-Psycho-Pedagogical Centres (CMPP), a Part-Time Therapeutic Reception Center (CATTP) and a Psychiatric Day Hospital (HJ). Overall, 581 first call forms and 73 patient files were analyzed (representing 654 children) and supplemented with illustrative interview excerpts from 59 family cases. RESULTS: Beyond descriptive elements (gender, age, school level, socio-family context, conditions of access to the centers, etc.), this study stressed the high vulnerability of some families, the range of reasons given for initial follow-up as well as the key role of educational institutions in screening and referring the population to mental health care. CONCLUSIONS: These results open up interesting insights into the early implementation of preventive measures and offer many research opportunities.


Assuntos
Transtornos Mentais/terapia , Serviços de Saúde Mental/estatística & dados numéricos , Saúde Pública/estatística & dados numéricos , Criança , Feminino , Humanos , Masculino , Paris , Pesquisa Qualitativa
17.
Sensors (Basel) ; 19(9)2019 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-31060334

RESUMO

[1-13C]pyruvate, the most widely used compound in dissolution-dynamic nuclear polarization (dDNP) magnetic resonance (MR), enables the visualization of lactate dehydrogenase (LDH) activity. This activity had been demonstrated in a wide variety of cancer models, ranging from cultured cells, to xenograft models, to human tumors in situ. Here we quantified the LDH activity in precision cut tumor slices (PCTS) of breast cancer xenografts. The Michigan Cancer Foundation-7 (MCF7) cell-line was chosen as a model for the luminal breast cancer type which is hormone responsive and is highly prevalent. The LDH activity, which was manifested as [1-13C]lactate production in the tumor slices, ranged between 3.8 and 6.1 nmole/nmole adenosine tri-phosphate (ATP) in 1 min (average 4.6 ± 1.0) on three different experimental set-ups consisting of arrested vs. continuous perfusion and non-selective and selective RF pulsation schemes and combinations thereof. This rate was converted to an expected LDH activity in a mass ranging between 3.3 and 5.2 µmole/g in 1 min, using the ATP level of these tumors. This indicated the likely utility of this approach in clinical dDNP of the human breast and may be useful as guidance for treatment response assessment in a large number of tumor types and therapies ex vivo.


Assuntos
Neoplasias da Mama/diagnóstico , Núcleo Celular/ultraestrutura , Lactato Desidrogenases/isolamento & purificação , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Núcleo Celular/química , Núcleo Celular/metabolismo , Polaridade Celular/efeitos dos fármacos , Liberação Controlada de Fármacos/efeitos dos fármacos , Feminino , Humanos , Lactato Desidrogenases/metabolismo , Imageamento por Ressonância Magnética , Camundongos , Ácido Pirúvico/isolamento & purificação , Ácido Pirúvico/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
18.
BMC Genet ; 19(1): 93, 2018 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-30340455

RESUMO

BACKGROUND: Pod constriction is an important descriptive and agronomic trait of peanut. For the in-shell Virginia marketing-type, this trait has commercial importance as well, since deeply constricted pods have a tendency to break, which makes them unmarketable. Classical genetic studies have indicated that pod constriction in peanut is controlled by one to four genes, depending on the genetic background. In all of those studies, pod constriction was evaluated visually as opposed to quantitatively. Here, we examined the genetic nature of this trait in the Virginia-type background. Our study involved 195 recombinant inbred lines (F7RILs) derived from two closely related cultivars that differ in their degree of pod constriction. Pod constriction was evaluated visually and quantitatively in terms of the pod constriction index (PCI), calculated as the average ratio between the pod's waist and shoulders. RESULTS: ANOVA and genetic parameters for PCI among the F7RILs in three blocks showed very significant genotypic effect (p(F) < 0.0001) and high heritability and genetic gain estimates (0.84 and 0.52, respectively). The mean PCI values of the different RILs had a bimodal distribution with an approximate 1:1 ratio between the two curves. Pod constriction was also determined visually (VPC) by grading the degree of each RIL as 'deep' or 'slight'. The χ2 test was found to not be significantly different from a 1:1 ratio (p = 0.79) as well. SNP-array-based technology was used to map this trait in the RIL population. A major locus for the pod constriction trait was found on chromosome B7, between B07_120,287,958 and B07_120,699,791, and the best-linked SNP explained 32% of the total variation within that region. Some discrepancy was found between the SNPs original location and the genetic mapping of the trait. CONCLUSION: The trait distribution and mapping, together with data from F1 and F2 generations indicate that in this background the pod constriction is controlled by a major recessive gene. The identity of loci controlling the pod constriction trait will allow breeders to apply marker-assisted breeding approaches to shift allelic frequencies towards a slighter pod constriction and will facilitate future effort for map-based gene cloning.


Assuntos
Arachis/genética , Cromossomos de Plantas , Mapeamento Cromossômico , Genótipo , Funções Verossimilhança , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Virginia
19.
Dev Psychopathol ; 30(1): 27-38, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28420452

RESUMO

Maternal depression negatively impacts children's development, yet few studies have focused on fathering and the family process in cases of maternal depression. A community cohort of married/cohabitating women was recruited on the second postbirth day (N = 1,983) and maternal depression repeatedly assessed across the first year and again at 6 years to form two cohorts: mothers chronically depressed from birth to 6 (N = 46) and nondepressed controls (N = 103). At 6 years, mother-child, father-child, and family interactions were observed. In families of depressed mothers, both mother and father exhibited lower sensitivity and higher intrusiveness, and children displayed lower social engagement during interactions with mother and father. Fathering moderated the effects of maternal depression on the family process. When fathers showed low sensitivity, high intrusiveness, and provided little opportunities for child social engagement, the family process was less cohesive, implying a decrease in the family's harmonious, warm, and collaborative style. However, in cases of high father sensitivity, low intrusiveness, and increased child engagement, the family process was unaffected by maternal depression. Findings describe both comparability and compensatory mechanisms in the effects of fathering on family life when maternal care is deficient, highlight the buffering role of fathers, and underscore the importance of father-focused interventions when mothers are depressed.


Assuntos
Transtorno Depressivo/psicologia , Família/psicologia , Relações Pai-Filho , Pai/psicologia , Mães/psicologia , Poder Familiar/psicologia , Adulto , Criança , Desenvolvimento Infantil , Pré-Escolar , Características da Família , Feminino , Humanos , Masculino , Comportamento Social
20.
Child Psychiatry Hum Dev ; 49(5): 779-785, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29468357

RESUMO

Maternal depression across the first years of life carries long-term negative consequences for children's well-being; yet, few studies focused on fathers as potential source of resilience in the context of chronic maternal depression. Utilizing an extreme-case design, a community birth cohort of married/cohabitating mothers (N = 1983) with no comorbid risk was repeatedly tested for maternal depression across the first year and again at 6 years, leading to two matched cohorts; 46 mothers with chronic depression and 103 non-depressed controls. At 6 years, mother and child underwent psychiatric diagnosis and mother-child and father-child interactions observed. Partners of depressed mothers exhibited reduced sensitivity, lower reciprocity, and higher tension during interactions, particularly among children with psychopathology. Maternal depression increased child propensity to display Axis-I disorder upon school-entry by fourfold. Sensitive fathering reduced this risk by half. Findings underscore the father's resilience-promoting role in cases of maternal depression and emphasize the need for father-focused interventions.


Assuntos
Filho de Pais com Deficiência/psicologia , Transtorno Depressivo/psicologia , Relações Pai-Filho , Pai/psicologia , Relações Mãe-Filho , Mães/psicologia , Adulto , Criança , Pré-Escolar , Depressão/psicologia , Saúde da Família , Feminino , Humanos , Lactente , Masculino , Psicopatologia
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