Prenatal Diagnosis of Infantile Neuroaxonal Dystrophy

Infantile Neuroaxonal Dystrophy (INAD1, MIM # 256600), is a rare autossomal recessive neurodegenerative disorder. The clinical picture is characterized by psychomotor regression and hypotonia, which progresses to spastic tetraplegia, visual impairment and dementia. Onset is within the first 2 years of life and death usually happens before the age of 10. In 2006, Morgan et al described that mutations in PLA2G6 gene localized in chromosome 22 (22q13), caused INAD1. Evidence showed that a large proportion of patients with infantile neuroaxonal dystrophy have a mutation in the PLA2G6 gene. A 36-years-old pregnant woman presented for obstetric follow up. It was the second pregnancy of this healthy, nonconsanguineous couple. Their 7 year-old daughter was affected with Infantile Neuroaxonal Dystrophy. Molecular testing was done in the child and, as a causal mutation was detected, it was possible to offer a specific prenatal diagnosis. The molecular study of PLA2G6 gene by amniocentesis showed the presence of a mutation in heterozygoty and the karyotype was normal for a female foetus. To our knowledge, this is the first molecular prenatal diagnosis of INAD1 in Portugal.

The role of inflammation in vascular function and pregnancy outcome in the pregnant stroke prone spontaneously hypertensive rat

During pregnancy, the maternal cardiovascular system undergoes major adaptation. One of these changes is a 40-50 % increase in circulating blood volume which requires a systemic remodelling of the vasculature in order to regulate maternal blood pressure and maximise blood supply to the developing placenta and fetus. These changes are broadly conserved between humans and rats making them an appropriate pre-clinical model in which to study the underlying mechanisms of pregnancy-dependent cardiovascular remodelling. Whilst women are normally protected against cardiovascular disease; pregnancy marks a period of time where women are susceptible to cardiovascular complications. Cardiovascular disease is the leading cause of maternal mortality in the United Kingdom; in particular hypertensive conditions are among the most common complications of pregnancy. One of the main underlying pathologies of these pregnancy complications is thought to be a failure of the maternal cardiovascular system to adapt. The remodelling of the uterine arteries, which directly supply the maternal-fetal interface, is paramount to a healthy pregnancy. Failure of the uterine arteries to remodel sufficiently can result in a number of obstetric complications such as preeclampsia, fetal growth restriction and spontaneous pregnancy loss. At present, it is poorly understood whether this deficient vascular response is due to a predisposition from existing maternal cardiovascular risk factors, the physiological changes that occur during pregnancy or a combination of both. Previous work in our group employed the stroke prone spontaneously hypertensive rat (SHRSP) as a model to investigate pregnancy-dependent remodelling of the uterine arteries. The SHRSP develops hypertension from 6 weeks of age and can be contrasted with the control strain, the Wistar Kyoto (WKY) rat. The phenotype of the SHRSP is therefore reflective of the clinical situation of maternal chronic hypertension during pregnancy. We showed that the SHRSP exhibited a deficient uterine artery remodelling response with respect to both structure and function accompanied by a reduction in litter size relative to the WKY at gestational day (GD) 18. A previous intervention study using nifedipine in the SHRSP achieved successful blood pressure reduction from 6 weeks of age and throughout pregnancy; however uterine artery remodelling and litter size at GD18 was not improved. We concluded that the abnormal uterine artery remodelling present in the SHRSP was independent of chronic hypertension. From these findings, we hypothesised that the SHRSP could be a novel model of spontaneously deficient uterine artery remodelling in response to pregnancy which was underpinned by other as yet unidentified cardiovascular risk factors. In Chapter 1 of this thesis, I have characterised the maternal, placental and fetal phenotype in pregnant (GD18) SHRSP and WKY. The pregnant SHRSP exhibit features of left ventricular hypertrophy in response to pregnancy and altered expression of maternal plasma biomarkers which have been previously associated with hypertension in human pregnancy. I developed a protocol for accurate dissection of the rat uteroplacental unit using qPCR probes specific for each layer. This allowed me to make an accurate and specific statement about gene expression in the SHRSP GD18 placenta; where oxidative stress related gene markers were increased in the vascular compartments. The majority of SHRSP placenta presented at GD18 with a blackened ring which encircled the tissue. Further investigation of the placenta using western blot for caspase 3 cleavage determined that this was likely due to increased cell death in the SHRSP placenta. The SHRSP also presented with a loss of one particular placental cell type at GD18: the glycogen cells. These cells could have been the target of cell death in the SHRSP placenta or were utilised early in pregnancy as a source of energy due to the deficient uterine artery blood supply. Blastocyst implantation was not altered but resorption rate was increased between SHRSP and WKY; indicating that the reduction in litter size in the SHRSP was primarily due to late (>GD14) pregnancy loss. Fetal growth was not restricted in SHRSP which led to the conclusion that SHRSP sacrifice part of their litter to deliver a smaller number of healthier pups. Activation of the immune system is a common pathway that has been implicated in the development of both hypertension and adverse pregnancy outcome. In Chapter 2, I proposed that this may be a mechanism of interest in SHRSP pregnancy and measured the pro-inflammatory cytokine, TNFα, as a marker of inflammation in pregnant SHRSP and WKY and in the placentas from these animals. TNFα was up-regulated in maternal plasma and urine from the GD18 SHRSP. In addition, TNFα release was increased from the GD18 SHRSP placenta as was the expression of the pro-inflammatory TNFα receptor 1 (Tnfr1). In order to investigate whether this excess TNFα was detrimental to SHRSP pregnancy, a vehicle-controlled intervention study using etanercept (a monoclonal antibody which works as a TNFα antagonist) was carried out. Etanercept treatment at GD0, 6, 12 and 18 resulted in an improvement in pregnancy outcome in the SHRSP with an increased litter size and reduced resorption rate. Furthermore, there was an improved uterine artery function in GD18 SHRSP treated with etanercept which was associated with an improved uterine artery blood flow over the course of gestation. In Chapter 3, I sought to identify the source of this detrimental excess of TNFα by designing a panel for maternal leukocytes in the blood and placenta at GD18. A population of CD3- CD161+ cells, which are defined as rat natural killer (NK) cells, were increased in number in the SHRSP. Intracellular flow cytometry also identified this cell type as a source of excess TNFα in blood and placenta from pregnant SHRSP. I then went on to evaluate the effects of etanercept treatment on these CD3- CD161+ cells and showed that etanercept reduced the expression of CD161 and the cytotoxic molecule, granzyme B, in the NK cells. Thus, etanercept limits the cytotoxicity and potential damaging effect of these NK cells in the SHRSP placenta. Analysing the urinary peptidome has clinical potential to identify novel pathways involved with disease and/or to develop biomarker panels to aid and stratify diagnosis. In Chapter 4, I utilised the SHRSP as a pre-clinical model to identify novel urinary peptides associated with hypertensive pregnancy. Firstly, a characterisation study was carried out in the kidney of the WKY and SHRSP. Urine samples from WKY and SHRSP taken at pre-pregnancy, mid-pregnancy (GD12) and late pregnancy (GD18) were used in the peptidomic screen. In order to capture peptides which were markers of hypertensive pregnancy from the urinary peptidomic data, I focussed on those that were only changed in a strain dependent manner at GD12 and 18 and not pre-pregnancy. Peptide fragments from the uromodulin protein were identified from this analysis to be increased in pregnant SHRSP relative to pregnant WKY. This increase in uromodulin was validated at the SHRSP kidney level using qPCR. Uromodulin has previously been identified to be a candidate molecule involved in systemic arterial hypertension but not in hypertensive pregnancy thus is a promising target for further study. In summary, we have characterised the SHRSP as the first model of maternal chronic hypertension during pregnancy and identified that inflammation mediated by TNFα and NK cells plays a key role in the pathology. The evidence presented in this thesis establishes the SHRSP as a pre-clinical model for pregnancy research and can be continued into clinical studies in pregnant women with chronic hypertension which remains an area of unmet research need.

Desenlaces en pacientes embarazadas con patología quirúrgica abdominal 2011-2014

Estudio transversal realizado entre 2011 y 2014 en la Clínica de la Mujer con el fin de describir el comportamiento de la salud el binomio madre hijo en gestantes que requirieron manejo quirúrgico de patologías quirúrgicas abdominales no ginecobstétricas.

Cistolitotomía percutánea en paciente con derivación urinaria compleja tipo mitrofanoff

Los cálculos vesicales son los más frecuentes del tracto urinario bajo (1). El factor predisponente más frecuente para la formación de cálculos vesicales es la obstrucción del tracto de salida. Presentaremos el caso de una paciente con antecedente de trauma uretral por fractura de pelvis; derivada con un Mitrofanoff; con diagnostico de cistolitiasis múltiple con cálculos de hasta 1 cm. El objetivo es mostrar la posibilidad de manejo de la cistolitiasis vía percutánea en una paciente con una derivación urinaria compleja funcionante, procedimiento menos mórbido, con menor tiempo de recuperación y con resultados comparables a otras técnicas. Inicia el procedimiento previa cateterización del Mitrofanoff con sonda Foley 12Fr, realizando punción suprapúbica para mediana izquierda a 2 cm de la rama púbica con aguja Chiba, posteriormente se avanzó guía hidrofílica seguida de varilla y dilatadores secuenciales de Alken 9Fr-27Fr y colocación de camisa Amplatz 28 Fr. Se retiraron dilatadores conservando guía de seguridad, se extrajeron la totalidad de los cálculos. Se ocluyó herida y se dejó sonda Foley conectada a Cystoflo. Egreso al día 1 post operatorio y retiro sonda Foley a los 5 días post operatorio. No se presentaron complicaciones, el tiempo operatorio fue de 1 hora, con 1 día de estancia hospitalaria. Recuperación satisfactoria con un resultado exitoso en cuanto a la extracción completa de los cálculos en 1 sólo tiempo quirúrgico. La cistolitotomía percutánea es una opción de manejo la cual ofrece grandes ventajas. Debe ser considerada no sólo en pacientes con acceso uretral restringido.

Asociación de las violencias física, sexual y comunitaria con el embarazo en adolescentes: análisis multinivel

Objetivos Determinar si existe asociación entre la exposición a violencia, experimentada a nivel individual o municipal, y el embarazo adolescente en mujeres Colombianas entre 13 y 19 años de edad que contestaron la Encuesta de Demografía y Salud en el año 2010. Métodos Estudio de corte transversal, nacional y multinivel. Se tomaron datos de dos niveles jerárquicos: Nivel- 1: Datos individuales de una muestra representativa de 13.313 mujeres entre 13 y 19 años de edad provenientes de La Encuesta Nacional de Demografía y Salud del año 2010 y Nivel- 2: Datos municipales de 258 municipios provenientes de las estadísticas vitales del DANE. Resultados La prevalencia del embarazo adolescente fue del 16.8% IC 95% [16.2-17.4]. El análisis mostró que la asociación entre embarazo adolescente y violencia tanto individual, representada como violencia sexual [OR= 6.99 IC99% 4.80-10.10] y violencia física [OR= 1.74 IC99% 1.47-2.05] así como la violencia municipal medida con tasas de homicidios altas [OR= 1.99 IC99% 1.29-3.07] y muy altas [OR= 2.10 IC99% 1.21-3.61] se mantuvo estadísticamente significativa después de ajustar por las variables: Edad [OR= 1.81 IC99% 1.71-1.91], ocupación [OR= 1.62 IC99% 1.37-1.93], educación primaria o sin educación [OR= 2.20 IC99% 1.47-3.30], educación secundaria [OR= 1.70 IC99% 1.24-2.32], asistir al colegio [OR= 0.18 IC99% 0.15-0.21], conocimiento en la fisiología reproductiva [OR= 1.28 IC99% 1.06-1.54], el índice de riqueza Q1, Q2, Q3 [OR= 2.18 IC99% 1.42-3.34], [OR= 2.00 IC99% 1.39-2.28], [OR= 1.82 IC99% 1.92-2.25] y alto porcentaje de Necesidades básicas insatisfechas a nivel municipal [OR= 2.34 IC99% 1.55-3.52]. Conclusiones Este estudio mostró una relación significativamente estadística entre la violencia sexual y física con el inicio de relaciones sexuales y embarazo adolescente después de controlar por factores sociodemográficos y conocimientos en reproducción sexual en mujeres colombianas de 13 a 19 años en el año 2010. Esta asociación debe continuar siendo estudiada para lograr optimizar las estrategias de prevención y disminuir la tasa actual de embarazos adolescentes en el país y sus consecuencias.

Prevalencia y factores asociados al síndrome de agotamiento profesional en residentes de diferentes especialidades médicas : una revisión de la literatura de los últimos 15 años

El Síndrome de Agotamiento Profesional (SAP), es común en los trabajadores de la salud, particularmente en los expuestos a altos niveles de estrés en el trabajo e incluye el agotamiento emocional, despersonalización y baja realización personal. Se considera que los médicos residentes presentan una mayor prevalencia del síndrome que los médicos debido a que se encuentran en entrenamiento, período en el cual están sometidos a alta carga laboral debido a las largas horas de trabajo, horarios irregulares, privación de sueño, intensas demandas emocionales, así como la presión de dominar un gran conocimiento clínico. Objetivo. Determinar la prevalencia del Síndrome de Agotamiento Profesional o Burnout en la población de médicos residentes. Metodología. Se realizó una búsqueda de artículos en la base de datos electrónica Pubmed, seleccionando aquellos publicados entre los años 2001 al 2016, tanto en idioma inglés como en español, a texto completo y enfocados en estudios en médicos residentes. Resultados. Los hallazgos sugieren que el Síndrome de Agotamiento Profesional o Burnout es altamente prevalente, que varía de acuerdo a la residencia que se esté realizando, encontrando un promedio del 50% con un rango de 27% a 75% entre las diferentes especialidades de la población estudiada y, en consecuencia, puede constituir un problema de salud que amerita atención en cada Institución, esto a pesar de que la prevalencia pueda variar de un lugar a otro y en las diferentes especialidades. Conclusiones. El SAP o Burnout constituye un problema de salud entre la población de médicos residentes, lo que sugiere la conveniencia de diseñar medidas para su prevención como informar en la inducción al programa de residencia sobre el riesgo de la aparición del síndrome y sus síntomas, consultar tempranamente ante signos de alarma, adecuar el sistema de vigilancia epidemiológica para que incluya esta condición específica y ajustar o disminuir la carga laboral entre otras.

Mover para melhor nascer: liberdade de movimentos e posições verticais no primeiro estádio do trabalho de parto

A Organização Mundial de Saúde destaca a deambulação e a adoção de posições verticais pela parturiente, como práticas demonstradamente benéficas, devendo ser estimuladas pela enfermeira obstetra na condução do trabalho de parto e parto normal, em situações de baixo risco obstétrico. O projeto preconizou a promoção da deambulação e o incentivo à adoção de posições verticais na fase ativa do trabalho de parto. As intervenções de enfermagem na promoção destas práticas foram avaliadas na equipa de enfermeiros obstetras do Serviço de Urgência Obstétrica e Ginecológica do Centro Hospitalar Barreiro-Montijo, Entidade Pública Empresarial e num grupo de parturientes, através da aplicação de questionários. As necessidades dos enfermeiros obstetras e das parturientes determinaram a realização de ações formativas e educacionais e a elaboração de materiais informativos de suporte à prática assistencial. A avaliação do projeto demonstrou que ainda existem práticas a serem melhoradas, sendo a sua continuidade vantajosa para profissionais e parturientes; ABSTRACT: TITLE: Move to Better Birth - Freedom of Movement and Upright Positions in First Stage of Labor. The World Health Organization highlights ambulation and adoption of vertical position by the woman, as demonstrated beneficial practices and should be encouraged by obstetric nurses in the conduct of obstetric labor and normal delivery, in low risk situations. The project advocated for the promotion of ambulation and encouragement for the adoption of vertical positions in the active phase of labor. Nursing interventions to promote these practices were evaluated in the obstetric nurses team of Obstetric and Gynecological Emergency Department from Hospital Center Barreiro-Montijo, Business Public Entity, and in a group of women in labor, through the use of questionnaires. The needs of obstetric nurses and women in labor determined the realization of training and educacional activities and the development of information materials to support the care practice. The project evaluation demonstrates that there are still practices to be improved, and its continuity being advantageous for professionals and women in labor.

O reiki para cuidar de quem cuida

“O Reiki para Cuidar de Quem Cuida” surge de vivências hospitalares de profissionais de saúde que solicitam e recorrem a sessões do Projeto “Terapia de Reiki/Shiatsu aos profissionais de Saúde do serviço de obstetrícia e bloco de partos”, referindo dores, stress, ansiedade e mal-estar. Objetivos: dar visibilidade ao Reiki como técnica terapêutica no cuidar e avaliar o Burnout dos profissionais de saúde antes e após sessão de Reiki. Metodologia: sensibilização para Reiki e Burnout, aplicação de questionários, tratamento de dados, pesquisa bibliográfica. Resultados: os profissionais de saúde necessitam de mais informação e de mais sessões de Reiki que referem ser muito úteis e promotoras de bem-estar; encontram-se em nível Médio de Burnout, reduzindo os valores após o Reiki. Conclusões: o Reiki reduz o Burnout, a sua inclusão na prática de enfermagem traduz-se em ganhos em saúde para si e para os utentes; ABSTRACT: Title: Reiki: Caring for Those who Care “Reiki: Caring for Those who Care” arised from health personnel’s experiences who request and resort to the project’s sessions “Reiki Therapy/Shiatsu to the Health Personnel of the Maternity and of the Obstetric/Gynecological Emergency Department”, who refer pain, stress, anxiety and malaise. Objectives: Presenting Reiki as a therapeutic technique in caring and evaluate health personnel’s Burnout before and after Reiki sessions. Methods: Raising awareness to Reiki and Burnout, questionnaires, data treatment, bibliographic research. Results: Health personnel need more information and more Reiki sessions, which refer being useful and wellbeing promoters; they experience a medium level of Burnout, having this value decreased after Reiki sessions. Conclusions: Reiki reduces Burnout, and its inclusion in the nursing practice results in health personnel’s and patient’s health outcomes.

Empoderamento da puérpera para o sucesso no aleitamento materno

São muitas as vantagens do aleitamento materno para a mãe e recém-nascido, havendo consenso de que a sua prática exclusiva deve ser até aos seis meses de vida. A intervenção teve como objetivo empoderar a puérpera para o sucesso no aleitamento materno. Foram aplicados três questionários a duas populações-alvo: um aos enfermeiros do Serviço de Obstetrícia do Centro Hospitalar Barreiro-Montijo, Entidade Pública Empresarial e outros dois às puérperas, que permitiram a recolha de informações sobre os conhecimentos dos enfermeiros acerca das práticas no aleitamento materno e da perceção das puérperas, quanto aos cuidados recebidos durante o internamento. Os resultados apontaram para a necessidade de formação dos enfermeiros sobre o aleitamento materno e a necessidade de empoderamento/acompanhamento no pós-parto. Desenvolveram-se atividades formativas e educacionais, quer para os profissionais, quer para as puérperas. A intervenção profissional revelou-se benéfica para a melhoria contínua dos cuidados de enfermagem na promoção do aleitamento materno exclusivo; EMPOWERMENT OF POSTPARTUM WOMEN FOR SUCCESSFUL BREASTFEEDING ABSTRACT: Breastfeeding presents several advantages to the mother and child, being generally agreed that its practice should be exclusive until six months of age. The goal of this intervention was to empower the puerpera towards breastfeeding success. Three questionnaires were applied to two populations: one to the nurses from the Obstetric Department of the Centro Hospitalar Barreiro-Montijo, Entidade Pública Empresarial and other two to puerperas, which allowed collection of information on the nurses’ knowledge about breastfeeding practices and the puerperas’ perception on received care during hospitalization. The results demonstrated the nurses’ need of training on breastfeeding and the need of empowerment/follow-up during the post-partum period. Educational and training activities, directed to professionals and puerperas, were developed. The professional intervention demonstrated benefits to the improvement of the nursing care in the promotion of exclusive breastfeeding.

Predizione degli outcome del rivolgimento per manovre esterne nelle gravidanze con presentazione podalica del feto con l'utilizzo dell'angolo di progressione della parte presentata

Introduzione: La presentazione podalica complica il 3-4% delle gravidanze singole a termine. Sebbene il parto vaginale sia possibile, gli studi in letteratura hanno riportato un aumento del rischio di mortalità e morbilità fetale. Di conseguenza nel mondo il numero di tagli cesarei eseguiti per presentazione podalica è alto. Il rivolgimento per manovre esterne (RME) è una procedura ostetrica sicura che permette il passaggio del feto dalla presentazione podalica a quella cefalica, riducendo il numero dei tagli cesarei. L’angolo di progressione della parte presentata (AoP) è un parametro ecografico descritto in letteratura per la valutazione della progressione della parte presentata attraverso il canale del parto ed è stato recentemente studiato nelle gravidanze con presentazione podalica del feto. Obiettivi: L’obiettivo primario è valutare la correlazione tra l’AoP e il successo del RME. L’obiettivo secondario è verificare se esiste correlazione tra parametri anamnestici ed ecografici e la riuscita del RME. Materiali e metodi: È stato condotto uno studio osservazione prospettico monocentrico, sono state reclutate previo consenso informato 54 pazienti afferenti presso l’Ospedale Maggiore di Bologna con gravidanza singola dopo le 36 settimane e feto in presentazione podalica tra gennaio 2020 e giugno 2023. Risultati: La percentuale di RME riusciti è stata del 48,2%, il 53,7% delle donne ha partorito mediante taglio cesareo. Non abbiamo trovato una correlazione tra AoP e successo del rivolgimento. Tra le altre variabili analizzate l’unica correlata al successo del RME è la quantità di liquido amniotico Conclusioni: Non abbiamo trovato una correlazione tra AOP e successo del RME. Come descritto in letteratura l’unico parametro ecografico che è risultato associato al successo del RME è la quantità di liquido amniotico. Dato il disegno dello studio e la scarsa numerosità del campione sono necessari ulteriori studi per confermare i risultati.

Adeguatezza e sostenibilità dell'alimentazione vegetale in gravidanza: una scoping review.

Introduzione: durante gli ultimi decenni, l’alimentazione vegetale ha acquisito sempre più popolarità tra individui di età e classi eterogenee, rappresentando ad oggi una scelta ben consolidata. Essa mira ad eliminare o quantomeno ridurre il consumo della carne e/o dei suoi derivati, a favore di una dieta più plant-based possibile, differenziandosi in svariati livelli di adesione. Obiettivo: portare alla luce le evidenze disponibili, al fine di indagare se l’alimentazione vegetale in gravidanza sia adeguata, sostenibile e sicura. Metodo: è stata condotta una scoping review, condotta nelle banche dati Pubmed, Medline, Cinahl, Trip Database e Scopus, con le parole chiave ‘Vegan’, ‘Vegetarian’, ‘Midwife’, ‘Pregnancy’, ‘Diet’, ‘Vegan diet’, ‘Plant-based diet’, ‘Vegetarian diet’, ‘Vegan pregnancy’, ‘Vegetarian pregnancy’, ‘Obstetric care’, ‘Counseling’, ‘Plant-based food’, ‘Health outcomes’, ‘Dietary intake’, ‘Nutritional status’, ‘Sustainability’, ‘Dietary patterns’. Sono stati selezionati 27 articoli, con disegni di studio differenti, che rispondevano adeguatamente alla domanda di ricerca. Risultati: l’alimentazione vegetale in gravidanza e allattamento è associata a numerosi outcomes positivi: un minor rischio di obesità pregravidica, eccessivo incremento ponderale, diabete di tipo 2 e gestazionale, patologie cardiovascolari e varie forme tumorali. Per massimizzare questi benefici, è necessario assicurare l’equilibrio energetico, l’adeguatezza nutrizionale e la giusta varietà di vegetali, frutta, cereali integrali, frutta secca e semi. Conclusioni: l’alimentazione vegetale risponde alle richieste dell’organismo e rappresenta in qualsiasi fase del ciclo vitale dell’individuo, compresa la gravidanza, una scelta adeguata e sostenibile, a condizione che segua uno schema ben pianificato. Difatti, quando organizzata e studiata con particolare attenzione ad alcuni nutrienti “critici”, è nutrizionalmente adeguata e apporta rilevanti benefici per la salute materno-fetale.