L’objectif de cette thèse a été d’étudier les caractéristiques et la spécificité des discours savants, élaborés au 18e siècle par des académiciens, des naturalistes, des médecins et des accoucheurs, sur la question des malformations physiques. Que signifie de façon plus concrète appartenir à la période positive1 pour l’écriture savante sur les êtres difformes. Nous avons procédé en trois temps et enquêté sur trois cadres discursifs différents : les mémoires académiques publiés à l’Académie Royale des Sciences à Paris, les traités d’histoire naturelle, les manuels d’accouchement et deux dissertations concernant la légitimité des naissances tardives. Dans ces espaces, l’importance accordée au corps difforme varie en fonction de l’ethos des auteurs, de leur approche méthodologique et selon les objectifs du cadre discursif dans lequel ils s’expriment.Le témoignage oculaire, la dissection et l’observation sont des paramètres centraux pour les académiciens qui examinent le corps difforme per se. Les traités d’histoire naturelle ont une envergure plus générale, les auteurs doivent prendre en considération une multitude des phénomènes. Dans le cadre de ce savoir les monstres deviennent une partie de la nature. La naturalisation des êtres malformés et leur considération comme des parties inhérentes à la nature continue l’idée que les monstres sont des êtres réels. Dans les discours qui concernent les naissances, les monstres sont présentés comme des cas pathologiques qui dérangent le déroulement normal de l’accouchement.Notre étude montre qu’en dépit de cette diversité qui implique également une évolution de la pensée sur les monstres, certaines lacunes, des manques et des non- dits marquent les discours savants de la période des Lumières. Plus particulièrement, l'examen des écrits permet de mieux saisir la dimension transitoire qui semble caractériser le 18e siècle; un siècle qui constitue un pont entre la période fabuleuse et la période scientifique. / The purpose of this work has been to study the characteristics and the specificity of learned discourses on monsters in Enlightened France. We wanted to describe and define the features of a positive period1 in the history on monsters. In order to answer this question we have focused on three learned frames of the 18th century: the academic papers published in the Royal Academy of Sciences of Paris, the treatises of natural history, the childbirth manuals and two dissertations on the topic of the legitimacy of late childbirths. In these three frames, the importance accorded to the deformed body depends on the author’s ethos, on his methodological approach and on the goals and aims of the discipline in which he is writing.We have seen that in the three discursive frames the authors insist on the real existence of the monsters which are carefully detached from fabulous connotations and from superstitions. The dissections and the observations are important ingredients in the work of the academicians who examine the deformed body per se. The natural history treatises adopt a general perspective and the authors deal with the immensity of the nature. In these general works the monsters become a component of nature and reflect its diversity. This naturalization of monsters underlines the fact that the malformations are seen as concrete defects which occur in nature even if the authors can’t propose any new explanations and theories for the malformations. In the childbirth manuals which have a didactic goal the authors consider the monstrous child in a pathological perspective and explain how to deliver it in the best given conditions.Our study has shown that despite the evolution and progress in the approach to the abnormal bodies, some gasps, deficiencies and unsaid things remain and denote of the transitory aspect of the 18th century thought on the topic on monsters. This positive period constitutes a chain or a phase between the fabulous period and the scientific period of the teratology which begins in the 19th century.

O objetivo deste trabalho foi investigar a ocorrência de mutações na sequência de nucleotídeos do gene AMELX, candidato a defeitos na formação do esmalte dentário, em indivíduos com e sem fissura labiopalatina. Para análise do gene proposto, foi coletado saliva de 165 indivíduos, que foram divididos em 4 grupos: Grupo 1 - composto por 46 indivíduos com fissura labiopalatina e malformação dentária; Grupo 2 - composto por 34 indivíduos com fissura labiopalatina e sem malformação dentária; Grupo 3 - composto por 34 indivíduos sem fissura labiopalatina e com malformação dentária e Grupo 4 - composto por 51 indivíduos sem fissura labiopalatina e malformação dentária. Foi realizada a extração do DNA genômico das amostras de saliva, seguido da PCR e sequenciamento direto. Cada mutação identificada no sequenciamento foi confirmada repetindo-se a reação de sequenciamento da fita antisenso. Após a coleta dos dados no Software SeqScape® 2.6, estes foram devidamente analisados por meio de gráficos e tabelas. Das amostras submetidas ao sequenciamento genético, obteve-se um aproveitamento de 95%, 90%, 89%, 88%, 94% e 100% destas amostras dos éxons 2, 3, 4, 5, 6 e 7, respectivamente. Dos 990 fragmentos sequenciados (seis éxons em 165 amostras de saliva), 918 fragmentos (93%) foram analisados. Detectou-se alteração na sequência de bases em 37 destes fragmentos (4%), sendo 14 no Grupo 1 (1,5%), 12 no Grupo 2 (1,3%), quatro no Grupo 3 (0,4%) e sete no Grupo 4 (0,7%), dos tipos missense e silenciosa, distribuídas nos éxons 2, 6 e 7 do gene AMELX, em oito distintos locais no cromossomo X. De acordo com os resultados obtidos do sequenciamento direto do gene AMELX, foi possível concluir que foram encontradas mutações na sequência de nucleotídeos do gene AMELX, em indivíduos com e sem fissura labiopalatina e malformação dentária. Observou-se ainda que a mutação localizada na posição 75 do éxon 6 esteve presente em todos os grupos estudados, sugerindo que, apesar de ser uma mutação silenciosa, pode ser um polimorfismo novo, a ser catalogado, pois foi detectado em 26 indivíduos, do total de 165, representando 16%. Entretanto, este estudo não pode afirmar que estas mutações alteraram diretamente o fenótipo dos pacientes dos grupos estudados. / The aim of this study was to investigate the occurrence of mutations in the AMELX candidate gene involved in enamel formation, in patients with and without cleft lip and palate and dental malformation. For gene analysis proposed was collected saliva from 165 patients who were divided in 4 groups: Group 1 - 46 individuals with cleft lip and palate and dental malformation, Group 2 - 34 individuals with cleft lip and palate without dental malformations; Group 3 - 34 individuals without cleft lip and palate with dental malformations and Group 4 - 51 individuals without cleft lip and palate and dental malformation. Next, genomic DNA was extracted from this saliva, followed by PCR and direct DNA sequencing. All samples with mutations were sequenced twice; once using the forward primer and a second time using the reverse primer. After data analysis with Software SeqScape® 2.6, the data were collated. Of the 165 samples, 95%, 90%, 89%, 88%, 94% and 100% of the samples were successfully sequenced from exons 2, 3, 4, 5, 6 and 7 respectively. Overall, of the 990 total sequenced exons (six exons in 165 samples of saliva), 918 exons (93%) were able to be completely sequenced and analyzed. Mutations were detected in 37 of the fragments (4%), more specifically, 14 in Group 1 (1.5%), 12 in Group 2 (1.3%), four in Group 3 (0.4%) and seven in Group 4 (0.7%), which included only missense and silent mutations, distributed throughout exons 2, 6 and 7 in the AMELX gene in eight different locations on chromosome X. According to the results obtained from direct sequencing of protein-coding exons of the AMELX gene, mutations were found in the nucleotide sequence of the AMELX gene in individuals with and without cleft lip and palate and dental malformation. It was also observed that the mutation in position 75 of exon 6 was present in all groups, suggesting that, though a silent mutation, may be a new polymorphism to be cataloged: it was found in 26 patients, the total of 165, representing 16%. However, this study cannot confirm that these mutations directly altered the phenotypes of the patients in the groups tested.

Hypospadias is a congenital malformation that occurs in 0.3-1% of live births, in which the meatus (the urethral opening) is dorsally malpositioned. Uncorrected hypospadias can cause difficulties in urination, abnormal sexual function, and adverse psychological consequences; surgical correction, though generally successful, constitutes an economic burden for families. Several common classes of pesticides have demonstrated potential to disrupt normal endocrine hormones that regulate fetal genitourinary development. Past epidemiologic studies of pesticide exposure and risk of hypospadias have been limited by limited available data, small sample sizes, or poor ascertainment of pesticide exposure. The objective of this study was to examine the relationship between parental occupational pesticide exposure and risk of hypospadias in their offspring; and further, to assess whether addition of residential pesticide exposure data is feasible and contributes to overall pesticide exposure. We began by conducting a meta-analysis of the current literature, in which summary measures of occupation (such as census occupation code) had been used to assign pesticide exposure. We found elevated but marginally significant risks of hypospadias were associated with maternal occupational exposure (PRR of 1.36, CI = 1.04-1.77), and paternal occupational exposure (PRR of 1.19, CI= 1.00-1.41) in the previously published literature. We then used industrial hygienist review of occupational histories to estimate the relationship between pesticide exposure and risk of hypospadias. We found that maternal occupational exposure to any pesticides (yes/no) was not associated with an increased risk of hypospadias (OR = 0.83, 95% CI = 0.6-1.1), cumulative insecticide (OR = 1.09; 95% CI = 0.9- 1.3), herbicide (OR = 1.05; 95% CI = 0.9- 1.2), or fungicide (OR = 0.91; 95% CI = 0.7-1.2) exposure. These negative findings might be explained by a lack of relationship at the low levels of exposure observed in this study population, in which case another farm exposure could be related to hypospadias; or this negative finding may be due to exposure misclassification. Finally, we evaluated the feasibility and relevance of collecting residential pesticide exposure and direct reports of occupational exposure from fathers. Residential pesticide use during the six months prior to pregnancy and during pregnancy was common among control mothers: 45% reported that their home had been treated for insect or rodent pests; 47% reported that their lawn or garden had been treated for weeds or insect pests; 16% used a lawn service; 26% reported that a pet had been treated for fleas, ticks, or mites (including flea and tick preventives); 17% reported community-wide sprayings for pests; and 16% reported that their workplaces were treated for pests. Case mothers were more likely to report that their home had been treated of insect or rodent pests (50%) or that a pet had been treated for fleas, ticks, or mites (36.5%). Our results suggest that collection of information on residential pesticide use is feasible, and the impact of residential pesticide use on birth defects risk should be assessed in future studies.

L’objectif de cette thèse était d’étudier les associations potentielles entre les traitements antirétroviraux reçus par les femmes enceintes infectées par le VIH et les complications pouvant survenir au cours de la grossesse ou être diagnostiquées dans la période néonatale. Ce travail est issu en majeure partie des données de l’Enquête Périnatale Française (ANRS-EPF), cohorte nationale multicentrique ayant inclus plus de 20 000 couples mères-enfants depuis 1986. Actuellement, presque toutes les femmes sont traitées par combinaisons antirétrovirales puissantes (cART ; 98% en 2013) et le taux de transmission est inférieur à 1% : 0.6% (IC95% : 0.4%-0.8% pour la période 2005-2013). La première partie portait sur le risque d’accouchement prématuré dont le taux a augmenté significativement entre la période 1990-1993 et 2005-2009, passant de 9.2% à 14.3%. Le risque d’accouchement prématuré était significativement associé au traitement par cART, par rapport aux monothérapies et bithérapies d’INTI, et au traitement débuté avant la conception par rapport aux traitements débutés en cours de grossesse. La survenue d’une cytolyse hépatique était fréquente (17%), et était liée à la fois à la prématurité, et au type de traitement, plus fréquentes avec les IP qu’avec les inhibiteurs non nucléosidiques de la transcriptase inverse. La perturbation du bilan hépatique pourrait être un facteur intermédiaire dans la relation entre traitements et accouchement prématuré. La seconde partie portait sur les malformations congénitales. D’une part, elle a permis de mettre en évidence une association entre exposition à l’efavirenz au premier trimestre de grossesse et les malformations neurologiques, bien que concernant peu de cas (n=4) et n’atteignant la significativité que dans une analyse de sensibilité. Cette association incite à maintenir une vigilance chez les enfants exposés in utero à cette molécule classée tératogène par la FDA mais prescrite de plus en plus largement. D’autre part, l’exposition au premier trimestre à la zidovudine était associée à la survenue de malformations cardiaques. La troisième partie a complété cette étude par une analyse de la fonction cardiaque, des modifications infracliniques de la contractilité et de l’épaisseur des parois du ventricule gauche ont été mises en évidence chez les enfants exposés in utero à une combinaison de traitement contenant la zidovudine et la lamivudine. Ces résultats ne remettent pas en question l’efficacité majeure des traitements antirétroviraux pour la prévention de la transmission de la mère à l’enfant du VIH, mais incitent à la poursuite d’une surveillance épidémiologique des effets indésirables potentiels, de manière à optimiser les prescriptions pour un meilleur rapport bénéfice/risque. / Our objective was to study potential associations between antiretroviral treatment and obstetrical or neonatal complications in a population of HIV-positive pregnant women. Most of the analyses were conducted with data from the French Perinatal Cohort (ANRS-EPF), an ongoing multicenter national cohort with more than 20 000 mother-infant pairs included since 1986. In the recent years, most women receive combination antiretroviral therapies (cART ; 98% en 2013) and the trasnsmission rate is consistently under 1% : 0.6% (IC95% : 0.4%-0.8% for 2005-2013). Risk of preterm birth was significantly associated with cART, when compared to NRTI monotherapy or dual therapy, and with timing of treatment, higher for women treated at conception than for those initiating treatment during pregnancy. The occurrence of liver enzyme elevation was frequent (17%), and was associated both with preterm birth and with PI-based treatment, when compared to NNRTIs. LEE could be an intermediate factor between cART and preterm birth. The second part of this work was a study of congenital birth defect in the cohort, and showed an association between first trimester-exposure to efavirenz and neurological defects, but this concerned small numbers (n=4), and reached significance only in a sensitivity analysis. This association encourages us to maintain awareness concerning this molecule, considered teratogenic by the FDA but more and more largely prescribed. We also reported an association between first-trimester exposure to zidovudine and congenital heart defects. In a third part, we studied heart function, differences in contractility and septum thickness of the left ventricle was found, among girls exposed to a combination containing zidovudine and lamivudineThese results do not question the great progress of antiretroviral treatment in the prevention of mother-to-child transmission, but they encourage us to continue epidemiologic surveillance of potential side effects, in order to optimize prescriptions for an improved benefit/risk ratio.

Pregnancy places great strain upon the body of a woman. Many things contribute to a successful pregnancy, such as healthy eating habits, healthy lifestyle, adequate physical activity, fresh air, good mental health. It is recommended to begin folic acid supplementation even before conception. Folic acid, known as folate, is one of the B vitamins. Pregnancy places greater need for folic acid intake, especially in the early stages, where insufficiency or even deficiency can manifest in a pathological pregnancy, oftentimes fatal. The specific link between the two is not yet very well known. However, several studies have confirmed that there is a positive effect that comes with increased folic acid intake before conception and during the first few weeks of pregnancy, most notably reduced occurrence of neural tube birth defects. General population generally doesn't have adequate intake of folic acid, so there is usually a folic acid deficit before and during pregnancy as well. This can be countered by consuming food high in folate, targeted food enrichment or direct consumption of supplements containing folic acid. The Czech Republic currently doesn't enrich food with folic acid, therefore it is recommended to increase its intake via supplementation. Research investigation through paper questionnaires...

Durante la pandemia COVID-19 se ha incrementado el uso de la telemedicina y de plataformas virtuales en el campo de la medicina, por ello en nuestra institución contamos con un sistema multicámara que permite la visualización en vivo de procedimientos endovasculares. Se realizaron once casos de aneurismas, malformaciones arteriovenosas y hematomas subdurales crónicos que fueron tratados y transmitidos en vivo sin problemas técnicos a través de la plataforma Zoom®. El tiempo promedio de transmisión y del número de participantes fue de 2.5 horas y 6 participantes, respectivamente. En todos los casos se discutió la técnica empleada y las complicaciones ocurridas. El aprendizaje remoto con plataformas en línea es hoy en día una herramienta importante, pero no un sustituto del aprendizaje práctico para procedimientos endovasculares. Recomendamos su implementación durante la pandemia de COVID-19 como un sustituto temporal, especialmente para los médicos en entrenamiento que no tienen acceso a intervenciones endovasculares avanzadas.

This thesis is focused on folic acid and its preventive effects on human health. Folic acid has many important functions in the human body and is especially important during pregnancy. It is essential for the proper development of the fetus and its adequate intake is the prevention of serious congenital malformations, such as neural tube defects, premature birth, abortion and other pathologies. The increased need for this vitamin is not easy to supplement with a regular diet. It is therefore recommended to take it in the form of food supplements (400-600 µg/day) during pregnancy and at least one month before the planned conception. For these reasons, it is necessary to focus on supporting the primary prevention of folic acid use, preferably in all fertile women. Folic acid also plays a crucial role in hematopoiesis and the main manifestation of its deficiency is megaloblastic anemia. Folic acid is further associated with the prevention of cardiovascular and cancer diseases and influencing the development of cognitive functions. The practical part of this thesis was focused on monitoring the saturation of pregnant women with this vitamin. The work contains a laboratory analysis of the content of the metabolite folic acid 5-methyltetrahydrofolate (5-MTHF) in the urine of pregnant women in order to...

A 3 year old Hispanic male presented with fevers, skin rash, left neck swelling and refusal to walk of several days duration. Physical exam revealed a febrile, fussy toddler with a tender, cystic lesion in the left submandibular region. Both ankles had tender cystic lesions on the lateral malleolar regions. Labs: WBC 33,000 with neutrophilia, bandemia, thrombocytosis, and increased ESR and CRP. MRI of the neck and ankles revealed cystic lymphatic malformations with no communication with the joints.ENT specialist was consulted and neck cystic lesion was aspirated to rule out a septic focus. Bone scan of the lower extremities ruled out infectious or malignant etiology. He was started on multiple antibiotics with a presumed diagnosis of sepsis. An ECHO on the 4th hospital day showed a pericardial effusion which required a pericardial window. He also developed bilateral pleural effusions which resolved with supportive treatment. Aspirates from the cystic lesions, pericardial fluid, blood and urine cultures were sterile. Even in the second week of hospital stay, he continued to spike high fevers (Tmax 107) with high white counts and left shift inspite of treatment with antibiotics. A diagnosis of systemic onset juvenile idiopathic arthritis (SOJIA) was made with input from rheumatologist. Antibiotics were discontinued and steroids were started with good response. Cystic lesions were treated with percutaneous sclerotherapy with doxycycline. He was discharged home on oral steroids, NSAID’s and weekly methotrexate. Etanercept was added to decrease dependence on oral steroids. He remains in good health 2 years since initial presentation. Discussion: A febrile toddler who refuses to walk is a common clinical presentation in pediatrics. Differential diagnosis of such a patient includes osteomyelitis, septic arthritis, acute rheumatic fever, leukemia and non-accidental trauma. The presence of systemic extra-articular symptoms as in our patient must alert the pediatrician to systemic onset juvenile rheumatoid arthritis (SOJIA). It accounts for 10-20% of all juvenile idiopathic arthritis (JIA) patients with an incidence of 0.4-0.8 per 100,000. SOJIA differs from other conditions in its multisystem involvement. Clinical features like pleurisy, pericarditis, spiking fevers, hepatosplenomegaly and lymphadenopathy overshadow the joint symptoms. The joint involvement may be completely absent or may be a late clinical feature. These patients have leukocytosis, thrombocytosis and high inflammatory markers simulating a septic focus. In our patient, the accurate diagnosis was complicated by the confounding presence of multiple cystic lymphatic lesions. Treatment of SOJIA is challenging. Oral steroids, NSAID’s, methotrexate, etanercept and the newer anakinra have been used with varying success. Our case underlines the importance of considering a diagnosis of systemic onset JIA in a febrile toddler even in the absence of overt joint involvement.

The aim of this study was to examine young men born between 1990-1995 with anorectal malformations (ARM) whom have undergone the new PSARP-operation starting in 1990, and how they experience their psychosocial and sexual health. The study also examines how they cope with their life situation and what their experience is of the health care and how they were responded to through out the years. This study is a qualitative research and consists seven semi- structured interviews with young men between sixteen and twenty years old. The analyses of this material resulted in three themes around which the study centers: psychosocial health, sexual health and the medical establishment and the informants thoughts about the proposition of counseling for themselves and other individuals born with ARM. The study shows that these young men have a good psychosocial health and a likely reason for that is good parental relationships and close friendships. It is difficult to draw any general conclusions about their sexual health, because there are several factors that played a role in this respect: there is a relatively widespread in their young age, their deformities are of various degrees and requires very different care and they have very different sexual experiences. However, there are factors which indicate that sexual health is affected by the congenital malformation. The study also showed that the young men have different coping strategies to manage their life situation in order to avoid exclusion and stigma. And that there are different needs for counseling among young ARM patients.

Purpose: Anorectal malformations (ARM) are one of the most challenging congenital malformations in pediatric surgery. We aimed to assess the research activity on ARM over the last five decades. Methods: Data on original research publications were retrieved from the Web of Science Core Collection (1970–2020), and analyzed for countries, authors, scientific journals, and top-ten papers. Scientific quantity was assessed by the number of publications. Research quality was estimated from the number of citations, average citation rate per item (ACI), and h-index. Results: A total number of 1595 articles with 19,419 citations (ACI = 12.2; h-index = 54) were identified. The annual number of publications and citations significantly increased over time (p < 0.0001). The USA (n = 386; 24.2%), Japan (n = 153; 9.6%), and China (n = 137; 8.6%) were the most productive countries; and the USA (n = 7850; ACI = 20.3; h-index = 44), Japan (n = 1937; ACI = 12.6; h-index = 21), and the Netherlands (n = 1318; ACI = 17.3; h-index = 22) were the top cited countries. Articles were preferentially published in JPS (n = 391; 24.5%), PSI (n = 181; 11.3%), and EJPS (n = 56; 3.5%). Top-ten cited papers focused on classification (n = 1), surgical technique (n = 3), associated syndromes (n = 2), postoperative outcome (n = 3), and basic research (n = 1). Conclusion: This bibliometric study provides valuable insights into the global development of ARM research, and shows that clinical studies and international collaborations dominate in this field.