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1.
Public Health Nutr ; 27(1): e8, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38050795

RESUMO

OBJECTIVE: To assess whether the Mediterranean Diet (MedDiet) is associated with lower micronutrients inadequacy in a sample of Spanish preschoolers. DESIGN: We conducted a cross-sectional study with 4-5-year-old children participating in the SENDO project. Information was gathered through an online questionnaire completed by parents. Dietary information was collected with a previously validated semi-quantitative FFQ. The estimated average requirements or adequate intake levels as proposed by the Institute of Medicine were used as cut-off point to define inadequate intake. STATISTICAL ANALYSES: Crude and multivariable adjusted estimates were calculated with generalised estimated equations to account for intra-cluster correlation between siblings. PARTICIPANTS: We used baseline information of 1153 participants enrolled in the SENDO project between January 2015 and June 2022. MAIN OUTCOMES MEASURES: OR and 95 % CI of presenting an inadequate intake of ≥ 3 micronutrients associated with the MedDiet. RESULTS: The adjusted proportion of children with inadequate intake of ≥ 3 micronutrients was 27·2 %, 13·5 % and 8·1 % in the categories of low, medium and high adherence to the MedDiet, respectively. After adjusting for all potential confounders, children who had a low adherence to the MedDiet showed a significant lower odds of inadequate intake of ≥ 3 micronutrients compared to those with a high adherence (OR 9·85; 95 % CI 3·33, 29·09). CONCLUSION: Lower adherence to the MedDiet is associated with higher odds of nutritional inadequacy.


Assuntos
Dieta Mediterrânea , Oligoelementos , Humanos , Pré-Escolar , Micronutrientes , Estudos Transversais , Inquéritos e Questionários
2.
Children (Basel) ; 10(10)2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37892374

RESUMO

Suboptimal micronutrient intake in children remains a public health concern around the world. This study examined the relationship between a previously defined dietary carbohydrate quality index (CQI) and the risk of micronutrient intake inadequacy in a pediatric cohort of Spanish preschoolers. Children aged 4-5 years old were recruited at their medical center or at school, and information on sociodemographic, dietary, and lifestyle variables were collected through a self-administered online questionnaire. Dietary information was obtained from a validated 147-item semi-quantitative food frequency questionnaire. We calculated the CQI and categorized participants into quartiles according to their scores. We assessed the intakes of 20 micronutrients and evaluated the probability of intake inadequacy by using the estimated average requirement cut-off point. Generalized estimating equations were used to adjust for potential confounders and account for the intra-cluster correlations between siblings. The adjusted proportions of children with an inadequate intake of ≥three micronutrients were 23%, 12%, 11%, and 9% in the first, second, third, and fourth quartiles of the CQI, respectively. Children in the highest quartile of the CQI had 0.22-fold lower odds (95% CI 0.10-0.48) of having ≥three inadequate micronutrient intakes than their peers in the lowest quartile. These findings reinforce the relevance of carbohydrate quality in children's diets.

3.
J Immunol ; 211(5): 844-852, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37477665

RESUMO

The lung is a barrier tissue with constant exposure to the inhaled environment. Therefore, innate immunity against particulates and pathogens is of critical importance to maintain tissue homeostasis. Although the lung harbors both myelinating and nonmyelinating Schwann cells (NMSCs), NMSCs represent the most abundant Schwann cell (SC) population in the lung. However, their contribution to lung physiology remains largely unknown. In this study, we used the human glial fibrillary acidic protein promoter driving tdTomato expression in mice to identify SCs in the peripheral nervous system and determine their location within the lung. Single-cell transcriptomic analysis revealed the existence of two NMSC populations (NMSC1 and NMSC2) that may participate in pathogen recognition. We demonstrated that these pulmonary SCs produce chemokines and cytokines upon LPS stimulation using in vitro conditions. Furthermore, we challenged mouse lungs with LPS and found that NMSC1 exhibits an enriched proinflammatory response among all SC subtypes. Collectively, these findings define the molecular profiles of lung SCs and suggest a potential role for NMSCs in lung inflammation.


Assuntos
Lipopolissacarídeos , Transcriptoma , Camundongos , Humanos , Animais , Lipopolissacarídeos/metabolismo , Células de Schwann/metabolismo , Pulmão
4.
Eur J Pediatr ; 182(8): 3537-3547, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37204600

RESUMO

Due to its rising prevalence, which parallels that of ultraprocessed food (UPF) consumption, inadequate micronutrient intake in childhood is a public health concern. This study aimed to evaluate the association between UPF consumption and inadequate intake of 20 micronutrients in a sample of children from the Mediterranean area. Cross-sectional information from participants in the "Seguimiento del Niño para un Desarrollo Óptimo" (SENDO) project 2015-2021 was used. Dietary information was gathered with a previously validated 147-item semi-quantitative food frequency questionnaire and the NOVA system was used to classify food items. Children were classified by tertiles of energy intake from UPF. Twenty micronutrients were evaluated, and inadequate intake was defined using the estimated average requirement as a cutoff. Crude and multivariable adjusted OR (95% CI) for the inadequacy of ≥ 3 micronutrients associated with UPF consumption were calculated fitting hierarchical models to take into account intra-cluster correlation between siblings. Analyses were adjusted for individual and family confounders. This study included 806 participants (51% boys) with a mean age of 5 years old (SD: 0.90) and an average energy intake from UPF of 37.64% (SD: 9.59). An inverse association between UPF consumption and the intake of 15 out of the 20 micronutrients evaluated was found (p < 0.01). After the adjustment for individual and family confounders, compared with children in the first tertile of UPF consumption, those in the third tertile showed higher odds of inadequate intake of ≥ 3 micronutrients (OR 2.57; 95%CI [1.51-4.40]).    Conclusion: High UPF consumption is associated with increased odds of inadequate intake of micronutrients in childhood. What is Known: • Micronutrient deficiency is among the 20 most important risk factors for disease and affect around two billion people worldwide. • UPF are rich in total fat, carbohydrates and added sugar, but poor in vitamins and minerals. What is New: • Compared with children in the 1st tertile of UPF consumption, those in the 3rd tertile had 2.57 times higher odds (95% CI: 1.51-4.40) of inadequate intake of ≥ 3 micronutrients after adjusting for potential confounders. • The adjusted proportions of children with inadequate intake of ≥ 3 micronutrients were 23%, 27% and 35% in the 1st, 2nd, and 3rd tertiles of UPF consumption respectively.


Assuntos
Alimento Processado , Micronutrientes , Masculino , Humanos , Criança , Pré-Escolar , Feminino , Estudos Transversais , Dieta , Ingestão de Energia , Fast Foods/efeitos adversos
5.
Pregnancy Hypertens ; 32: 64-69, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37116297

RESUMO

BACKGROUND: Preeclampsia remains the leading cause of maternal morbidity and mortality. Consequently, research has focused on validating tools to predict maternal outcomes regarding clinical and biochemical features from the maternal compartment. However, preeclampsia also leads to neonatal complications due to placental insufficiency and prematurity, being the early-onset type associated with the poorest outcome. Hence, it is imperative to study whether these existing tools can predict adverse neonatal outcome. OBJECTIVE: To assess the predictive value for adverse neonatal outcome of Doppler ultrasound, angiogenic factors and multi-parametric risk-score models in women with early-onset severe preeclampsia. STUDY DESIGN: This is a prospective cohort study of consecutive singleton pregnancies complicated by early-onset (developed before 34 week's gestation) severe preeclampsia. RESULTS: 63 women with early-onset severe preeclampsia, 18 (28.6%) presented an adverse neonatal outcome. Placental growth factor (PlGF) showed the best discrimination between neonatal outcomes among angiogenic factors. PREP-L score is a multi-parametric risk-score for the prediction of complications in early-onset preeclampsia which includes maternal characteristics and clinical and analytical data obtained at admission. Good predictive values for the prediction of neonatal complications were found with the combination of PREP-L score with advanced Doppler (AUC ROC 0.9 95% CI 0.82-0.98]) and with PlGF levels (AUC ROC 0.91 [95% CI 0.84-0.98]). CONCLUSIONS: The combination of maternal risk scoring (PREP-L score) with angiogenic factors or fetal Doppler ultrasound at the time of diagnosis of early-onset preeclampsia with severe features performs well in predicting adverse neonatal outcome.


Assuntos
Insuficiência Placentária , Pré-Eclâmpsia , Recém-Nascido , Gravidez , Feminino , Humanos , Pré-Eclâmpsia/diagnóstico , Fator de Crescimento Placentário , Estudos Prospectivos , Placenta/metabolismo , Biomarcadores , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo
6.
Nat Commun ; 14(1): 366, 2023 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-36690629

RESUMO

Sensory neurons of the dorsal root ganglion (DRG) are critical for maintaining tissue homeostasis by sensing and initiating responses to stimuli. While most preclinical studies of DRGs are conducted in rodents, much less is known about the mechanisms of sensory perception in primates. We generated a transcriptome atlas of mouse, guinea pig, cynomolgus monkey, and human DRGs by implementing a common laboratory workflow and multiple data-integration approaches to generate high-resolution cross-species mappings of sensory neuron subtypes. Using our atlas, we identified conserved core modules highlighting subtype-specific biological processes related to inflammatory response. We also identified divergent expression of key genes involved in DRG function, suggesting species-specific adaptations specifically in nociceptors that likely point to divergent function of nociceptors. Among these, we validated that TAFA4, a member of the druggable genome, was expressed in distinct populations of DRG neurons across species, highlighting species-specific programs that are critical for therapeutic development.


Assuntos
Gânglios Espinais , Transcriptoma , Camundongos , Humanos , Animais , Cobaias , Gânglios Espinais/metabolismo , Macaca fascicularis , Nociceptores/metabolismo , Células Receptoras Sensoriais/metabolismo , Sensação , Citocinas/metabolismo
7.
Public Health Nutr ; : 1-22, 2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35618704

RESUMO

BRACKGROUND: Ultra-processed food (UPF) consumption is increasing exponentially, becoming a matter of concern for Public Health, given its adverse health effects. OBJECTIVE: To identify individual and family factors predicting UPF consumption in childhood. DESIGN: The SENDO project is an ongoing prospective dynamic cohort of Spanish children. In this study, we used baseline information of participants recruited between January 2015 and June 2021. Dietary information was collected with a validated semi-quantitative FFQ, and food items were classified using the NOVA classification. Individual and family factors associated with UPF consumption (p< 0.20) in univariate analyses were introduced in a model of generalized estimating equations (GEE) which accounted for intra-cluster correlations between siblings. SETTING: The SENDO proyect (Spain), 2015-2021. PARTICIPANTS: Spanish children are recruited at the age of 4-5 years and followed yearly through online questionnaires completed by parents. RESULTS: In this sample of 806 participants (49% girls; mean age 5 years [SD: 0.90]), the mean UPF consumption was 37.64 % of total energy intake (sd: 9.59). Large family size and longer exposure to screens predicted higher consumption of UPF. On the other hand, better knowledge of children's dietary recommendations, healthy dietary attitudes towards child's eating habits and longer breastfeeding were associated with lower consumption of UPF. All these factors accounted for approximately 16% of the variability on the consumption of UPF in childhood. CONCLUSION: Since most of the factors identified in this study are modifiable, they should be considered in public health strategies aimed at promoting heathy dietary habits in early life.

8.
Arthritis Res Ther ; 24(1): 91, 2022 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-35477585

RESUMO

BACKGROUND: Pregnancy in systemic sclerosis (SSc) patients is no more an infrequent event as it used to be, but literature data on pregnancy outcomes in women with SSc are scarce. The rate of preterm deliveries and intrauterine growth restriction (IUGR) seems to be increased, while the risk of miscarriages is controversial. Moreover, no study compared pregnancy outcomes in SSc with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). We performed a retrospective study to compare the pregnancy and disease outcomes of women with SSc with a cohort of age-matched women with systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and healthy controls (HC). METHODS: A total of 154 pregnancies from SSc, SLE, APS patients, and HC were prospectively followed at the High-Risk Pregnancy Unit of our center from 2008 to 2019. The primary outcome was a composite endpoint of miscarriages, fetal deaths, intrauterine growth restriction (IUGR), preeclampsia, neonatal deaths, preterm birth, and small-for-gestational-age (SGA) newborns. Single adverse pregnancy outcomes (APO) represented secondary endpoints. SSc activity variations in relation to pregnancy were assessed. RESULTS: The risk of APO was significantly higher in SSc patients compared to HC (60.6% vs 10.0%; OR = 14.42; 95% CI 3.70-56.18, p = 0.001) and SLE patients (60.6% vs 37.5%; OR = 3.56; 95% CI 1.29-9.83, p = 0.014). Compared to HC, women with SSc had an increased frequency of first trimester miscarriage (15% vs 0 %; p = 0.016), preeclampsia (12% vs 0%, p = 0.038), and SGA newborns (21.2% vs 0%; p = 0.003). Preterm deliveries were more frequent in SSc pregnancies in comparison with HC (24.2% vs 5%; OR = 6.08; 95% CI 1.19-31.02, p = 0.036) and SLE patients (24.2% vs 7.5%, OR = 5.68; 95% CI 1.1-29.38, p = 0.038). Disease remained stable in all SSc patients during pregnancy and up to 1 year after delivery. CONCLUSIONS: We found an increased risk of APO in our SSc cohort in comparison with HC (with higher rates of miscarriages, preeclampsia, SGA newborns, and preterm deliveries) and SLE patients (presenting a higher rate of preterm deliveries). High-risk multidisciplinary management of SSc pregnant women is highly recommended.


Assuntos
Aborto Espontâneo , Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Pré-Eclâmpsia , Nascimento Prematuro , Escleroderma Sistêmico , Aborto Espontâneo/epidemiologia , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/epidemiologia , Feminino , Retardo do Crescimento Fetal/epidemiologia , Humanos , Recém-Nascido , Gravidez , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/epidemiologia
9.
World J Pediatr ; 18(7): 482-489, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35334044

RESUMO

BACKGROUND: The association between parental perception of child's weight and their attitudes towards his/her dietary habits has not been reported yet. This study aimed to assess the association between parental underestimation of child's weight and parental attitudes towards child's dietary habits. METHODS: We conducted a cross-sectional analysis of SENDO cohort participants recruited between January 2015 and June 2020. All information was collected through online questionnaires completed by parents. We calculated crude and multivariable-adjusted odds ratio (OR) and 95% confidence intervals (CI) for unhealthy attitudes towards child's dietary habits associated with parental underestimation of child's weight. RESULTS: Sixteen percent of children in the SENDO project had parents who underestimated their weight. Parents who underestimated their child's weight status were more likely to have unhealthy attitudes toward his/her dietary habits [OR 3.35; 95% CI (1.71-6.53)]. CONCLUSIONS: Parental underestimation of child's weight was associated with unhealthy attitudes towards child's dietary habits. Pediatricians and public health practitioners should pay attention to the parental perception of child's weight to identify parents who underestimate it as an at-risk group in which to inquire about lifestyle and dietary habits.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Pais , Índice de Massa Corporal , Peso Corporal , Criança , Estudos Transversais , Comportamento Alimentar , Feminino , Humanos , Masculino , Obesidade , Sobrepeso , Percepção , Inquéritos e Questionários
10.
Acta méd. colomb ; 47(1): 55-57, ene.-mar. 2022. graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1374105

RESUMO

Resumen La diarrea crónica es una patología frecuente con un amplio diagnóstico diferencial. Presentamos el caso de un paciente con diarrea crónica secundaria a enterocolopatía por la toma prolongada de olmesartán. Se trata de una patología infradiagnosticada por desconocimiento de la entidad, pero que debe considerarse en base a la frecuencia de uso del grupo farmacológico. En nuestro caso, la buena evolución clínica tras la retirada del fármaco nos muestra la necesidad de considerarlo como causa directa del cuadro clínico. Un adecuado enfoque terapéutico en estos pacientes nos permitirá evitar pruebas complementarias, costos innecesarios y se traducirá en una mejora diagnóstica y del pronóstico de estos pacientes. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2203).


Abstract Chronic diarrhea is a common pathology with a broad differential diagnosis. We present the case of a patient with chronic diarrhea secondary to enteropathy due to prolonged consumption of olmesartan. This is an underdiagnosed pathology due to lack of knowledge regarding this entity, but it should be considered, given the frequency with which this pharmacological group is used. In our case, the favorable clinical progression after withdrawing the medication indicates the need to consider it as the direct cause of the clinical picture. An appropriate therapeutic approach to these patients will allow us to avoid complementary tests and unnecessary costs, and will translate into a better diagnosis and prognosis in these patients. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2203).

11.
Physiol Rep ; 9(18): e15022, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34558216

RESUMO

Pulmonary vein (PV) stretch is proarrhythmic for atrial fibrillation (AF). AF patients often report that a left lateral (LL) body position can trigger arrhythmia symptoms. Because the PV myocardium is thought to trigger AF, we hypothesized that the LL compared to the supine body position increases PV wall stress. Functional cardiac magnetic resonance imaging was performed in supine and LL recumbent body position in awake condition in healthy human volunteers (n = 20). Following a change from supine to LL position, the heart moved in an anterior-LL direction in the thorax. The right superior PV diameter was increased by 19% (24.6 ± 3.1 vs. 20.7 ± 3.2 mm, p = 0.009) and left atrial (LA) volume was larger by 17% (61.7[15.4] vs. 51.0[17.8] ml, p = 0.015) in LL than supine position, respectively. The passive LA conduit fraction (normalized difference between maximum and pre-contraction LA volume) increased by 25% in LL compared to supine position (19.6 ± 9.0 vs. 15.7 ± 7.6%, respectively, p = 0.016). Local wall stress in the PV regions increased in LL compared to supine position (overall mean: 1.01 ± 0.12 vs. 1.10 ± 0.10 arb. unit, LL vs. supine, position effect p = 0.041), whereas this was not the case in the LA walls (overall mean: 1.18 ± 0.31 vs. 1.21 ± 0.21 arb. unit, LL vs. supine, position effect p = 0.381). In conclusion, a left lateral body position increases PV myocardial stress during the atrial relaxation phase of healthy volunteers. These results have implications for the mechanisms of posture-triggered AF.


Assuntos
Frequência Cardíaca , Veias Pulmonares/fisiologia , Decúbito Dorsal , Circulação Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica , Veias Pulmonares/diagnóstico por imagem , Estresse Fisiológico , Vasoconstrição
13.
Front Physiol ; 12: 708650, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335312

RESUMO

Background: Because stretch of the atrial myocardium is proarrhythmic for atrial fibrillation (AF) and a left lateral body position increases atrial dimensions in humans, we hypothesized that left lateral recumbence is a frequent AF-triggering body position in AF patients. Methods: We performed a questionnaire study of symptomatic paroxysmal AF (episodes of AF < 1 week) patients scheduled for a first AF ablation therapy at Catharina Hospital, Eindhoven, the Netherlands and at University Hospital, Bordeaux, France. Results: Ninety-four symptomatic paroxysmal AF patients were included [mean age 61 ± 11 years, median AF history of 29(48) months, 31% were females]. Twenty-two percent of patients reported a specific body position as a trigger of their AF symptoms. The triggering body position was left lateral position in 57% of cases, supine position in 33%, right lateral position in 10%, and prone position in 5% (p = 0.003 overall difference in prevalence). Patients with positional AF had a higher body mass index compared to patients without nocturnal/positional AF [28.7(4.2) and 25.4(5.2) kg/m2, respectively, p = 0.025], but otherwise resembled these patients. Conclusion: Body position, and the left lateral position, in particular, is a common trigger of AF in symptomatic AF patients. Moreover, positional AF is associated with overweight. Understanding of the underlying mechanisms of positional AF can contribute to AF treatment and prevention.

14.
Pediatr. aten. prim ; 23(90): 133-142, abr.- jun. 2021. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-222755

RESUMO

Introducción: existe controversia sobre si la lactancia materna (LM) prolongada puede ser un factor de riesgo de caries. La LM se recomienda hasta al menos los dos años y tiene demostrados beneficios sobre la salud, incluida la bucodental. Repasamos la evidencia científica y presentamos los resultados de nuestra cohorte. Métodos: cohorte prospectiva, abierta y multipropósito de niños de 4-5 años, cuyos padres responden a cuestionarios autorreferidos acerca de hábitos nutricionales y estilo de vida. Análisis retrospectivo de prevalencia de caries según duración de LM. Ajustamos por edad, sexo, raza, conocimientos nutricionales y actitudes dietéticas de los padres, adhesión a la dieta mediterránea, ingesta energética total y de azúcar. Resultados: se alcanzó un tamaño muestral de 370 participantes, 50 de los cuales había tenido, al menos una caries. La LM hasta los 12 meses se asociaba con un menor riesgo de caries, pero la LM de más de 12 meses se asociaba con un riesgo mayor (odds ratio [OR]: 2,75; intervalo de confianza del 95% [IC 95]: 1,397 a 5,44; p = 0,003). La ingesta energética total o la de azúcar no resultaron ser confusores importantes para la asociación estudiada. La adhesión a dieta mediterránea puede tener un efecto protector, hace falta más investigación al respecto. Conclusiones: existe una asociación directa estadísticamente significativa entre la LM de más de 12 meses y el riesgo de caries. Sin embargo, la LM hasta los 12 meses es un factor protector. Los resultados obtenidos son consistentes con la literatura médica existente (AU)


Introduction and objectives: there is debate whether prolonged breastfeeding is a risk factor for caries. Breastfeeding, recommended for at least two years, has been associated with several benefits, including in oral health. We reviewed the literature on the subject, and present the results observed in the cohort under study.Methods: study conducted in a prospective, open-enrolment and multipurpose cohort of children aged 4-5 years, whose parents completed a self-administered questionnaire regarding diet and lifestyle habits. We performed a retrospective analysis of the prevalence of caries based on the duration of breastfeeding. We adjusted the analysis by age, sex, race, parental knowledge and attitudes, total energy and sugar intake and adherence to the Mediterranean diet.Results: the sample included 370 children, of who 50 had developed caries. Breastfeeding up to 12 months was associated with a lower risk of caries, but breastfeeding longer than 12 months was associated with an increased risk (OR 2.75; 95 IC: 1.397 - 5.44; p = 0.003). The total energy and sugar intakes were not significant confounders in the association under study. Adherence to the Mediterranean diet may have a protective effect, but more research is needed to confirm it.Conclusions: we found a significant direct association between breastfeeding for more than 12 months and the prevalence of caries. However, breastfeeding for less than 12 months had a protective effect. Our findings were consistent with the previous litera ture. (AU)


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Dieta Mediterrânea , Cárie Dentária/etiologia , Cárie Dentária/epidemiologia , Lactação , Inquéritos e Questionários , Estudos Prospectivos , Estudos de Coortes , Fatores de Risco , Prevalência , Espanha/epidemiologia
15.
Rev Esp Enferm Dig ; 113(10): 734, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33866792

RESUMO

Wereport the case of a 59-year-old male with cholelithiasis, choledocholithiasis, and biliary obstruction due to enolic chronic pancreatitis. He was treated 7 years previously with cholecystectomy, ERCP, and a fully-coated biliary metal stent for 6 months.


Assuntos
Coledocolitíase , Ducto Cístico , Colangiografia , Colangiopancreatografia Retrógrada Endoscópica , Colecistectomia , Coledocolitíase/complicações , Coledocolitíase/diagnóstico por imagem , Coledocolitíase/cirurgia , Ducto Cístico/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade
16.
J Med Chem ; 64(7): 3843-3869, 2021 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-33749283

RESUMO

Transient receptor potential ankyrin 1 (TRPA1) is a nonselective calcium-permeable ion channel highly expressed in the primary sensory neurons functioning as a polymodal sensor for exogenous and endogenous stimuli and has generated widespread interest as a target for inhibition due to its implication in neuropathic pain and respiratory disease. Herein, we describe the optimization of a series of potent, selective, and orally bioavailable TRPA1 small molecule antagonists, leading to the discovery of a novel tetrahydrofuran-based linker. Given the balance of physicochemical properties and strong in vivo target engagement in a rat AITC-induced pain assay, compound 20 was progressed into a guinea pig ovalbumin asthma model where it exhibited significant dose-dependent reduction of inflammatory response. Furthermore, the structure of the TRPA1 channel bound to compound 21 was determined via cryogenic electron microscopy to a resolution of 3 Å, revealing the binding site and mechanism of action for this class of antagonists.


Assuntos
Asma/tratamento farmacológico , Furanos/uso terapêutico , Purinas/uso terapêutico , Canal de Cátion TRPA1/antagonistas & inibidores , Animais , Asma/induzido quimicamente , Asma/complicações , Células CHO , Cricetulus , Furanos/síntese química , Furanos/metabolismo , Cobaias , Humanos , Inflamação/tratamento farmacológico , Inflamação/etiologia , Ligantes , Masculino , Estrutura Molecular , Ovalbumina , Oxidiazóis/síntese química , Oxidiazóis/metabolismo , Oxidiazóis/uso terapêutico , Ligação Proteica , Purinas/síntese química , Purinas/metabolismo , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Canal de Cátion TRPA1/metabolismo
17.
J Paediatr Child Health ; 57(6): 819-825, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33426731

RESUMO

AIM: The association between caesarean delivery and the risk of overweight/obesity in the offspring has been previously reported using conventional measures of association (relative risks or odds ratios). We aimed at refining the existing evidence by calculating the marginal effect of the exposure and estimating the unmeasured residual confounding. METHODS: In the 'SEguimiento del Niño para un Desarrollo Óptimo' Project, a dynamic multipurpose paediatric cohort study, we collected information from parents through self-administered online questionnaires. We estimated the offspring's risk of overweight/obesity at age 4-6 years, associated with the type of delivery through marginal effect of the exposure. Unmeasured residual confounding was assessed using the E-value. RESULTS: Among 407 participants (mean-age: 5.0 years (standard deviation: 0.9)), 86 (21.1%) were born by caesarean delivery. Children born by caesarean delivery had higher odds of overweight/obesity than those born vaginally. Subgroup analyses showed similar results. The multivariable adjusted marginal effect showed that caesarean delivery was associated with an 8.0% (95% confidence interval: 0.2-15.7) absolute increase in the prevalence of overweight/obesity. The estimated residual confounding showed an E-value of 4.03, higher than the OR obtained for all the confounding factors we accounted for. CONCLUSIONS: Caesarean delivery was associated with an 8% absolute increase in the risk of overweight/obesity that is very unlikely explained by residual confounding.


Assuntos
Obesidade Infantil , Peso ao Nascer , Índice de Massa Corporal , Cesárea , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Sobrepeso/epidemiologia , Sobrepeso/etiologia , Obesidade Infantil/epidemiologia , Obesidade Infantil/etiologia , Gravidez , Prevalência , Fatores de Risco
19.
Cell ; 181(3): 517-519, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32359435

RESUMO

Some children with autism spectrum disorder (ASD) show behavioral improvements when experiencing inflammation accompanied by fever; however, little is known about the mechanisms that underlie these beneficial effects. In a recent issue of Nature, Reed and colleagues demonstrate that the production of interleukin-17 (IL-17) during inflammation promotes social behavior in mouse models of neurodevelopmental disorders.


Assuntos
Transtorno do Espectro Autista , Transtornos do Neurodesenvolvimento , Animais , Criança , Citocinas , Humanos , Interleucina-17 , Camundongos , Comportamento Social
20.
Sci Rep ; 10(1): 979, 2020 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-31969645

RESUMO

The transient receptor potential (TRP) superfamily of ion channels has garnered significant attention by the pharmaceutical industry. In particular, TRP channels showing high levels of expression in sensory neurons such as TRPV1, TRPA1, and TRPM8, have been considered as targets for indications where sensory neurons play a fundamental role, such as pain, itch, and asthma. Modeling these indications in rodents is challenging, especially in mice. The rat is the preferred species for pharmacological studies in pain, itch, and asthma, but until recently, genetic manipulation of the rat has been technically challenging. Here, using CRISPR technology, we have generated a TRPA1 KO rat to enable more sophisticated modeling of pain, itch, and asthma. We present a detailed phenotyping of the TRPA1 KO rat in models of pain, itch, and asthma that have previously only been investigated in the mouse. With the exception of nociception induced by direct TRPA1 activation, we have found that the TRPA1 KO rat shows apparently normal behavioral responses in multiple models of pain and itch. Immune cell infiltration into the lung in the rat OVA model of asthma, on the other hand, appears to be dependent on TRPA1, similar to was has been observed in TRPA1 KO mice. Our hope is that the TRPA1 KO rat will become a useful tool in further studies of TRPA1 as a drug target.


Assuntos
Asma/genética , Comportamento Animal/fisiologia , Dor/genética , Prurido/genética , Canal de Cátion TRPA1/genética , Animais , Asma/metabolismo , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Dor/metabolismo , Fenótipo , Prurido/metabolismo , Ratos , Ratos Transgênicos , Canal de Cátion TRPA1/metabolismo
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