RESUMEN
The influence of testosterone on the development of human brain lateralization has been subject of debate for a long time, partly because studies investigating this are necessarily mostly correlational. In the present study we used a quasi-experimental approach by assessing functional brain lateralization in trans boys (female sex assigned at birth, diagnosed with Gender Dysphoria, n = 21) before and after testosterone treatment, and compared these results to the functional lateralization of age-matched control groups of cisgender boys (n = 20) and girls (n = 21) around 16 years of age. The lateralization index of the amygdala was determined with functional magnetic resonance imaging (fMRI) during an emotional face matching task with angry and fearful faces, as the literature indicates that boys show more activation in the right amygdala than girls during the perception of emotional faces. As expected, the lateralization index in trans boys shifted towards the right amygdala after testosterone treatment, and the cumulative dose of testosterone treatment correlated significantly with amygdala lateralization after treatment. However, we did not find any significant group differences in lateralization and endogenous testosterone concentrations predicted rightward amygdala lateralization only in the cis boys, but not in cis girls or trans boys. These inconsistencies may be due to sex differences in sensitivity to testosterone or its metabolites, which would be a worthwhile course for future studies.
Asunto(s)
Amígdala del Cerebelo/efectos de los fármacos , Testosterona/farmacología , Personas Transgénero/psicología , Adolescente , Amígdala del Cerebelo/metabolismo , Encéfalo/metabolismo , Emociones/fisiología , Expresión Facial , Femenino , Lateralidad Funcional/efectos de los fármacos , Disforia de Género/fisiopatología , Identidad de Género , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Hombres , Caracteres Sexuales , Testosterona/metabolismo , Transexualidad/tratamiento farmacológico , Transexualidad/metabolismo , MujeresRESUMEN
Despite the growing evidence for the importance of developmental experiences shaping consistent individual differences in behaviour and physiology, the role of endocrine factors underlying the development and maintenance of such differences across multiple traits, remains poorly understood. Here, we investigated how an experimental manipulation of circulating glucocorticoids during early adolescence affects behavioural and physiological variation and covariation later in life in the precocial cavy (Cavia aperea). Plasma cortisol concentrations were experimentally elevated by administering cortisol via food for 3â¯weeks. Struggle docility, escape latency, boldness, exploration and social behaviour were then tested three times after individuals attained sexual maturity. In addition, blood samples were taken repeatedly to monitor circulating cortisol concentrations. Exogenous cortisol affected mean trait expression of plasma cortisol levels, struggle docility and escape latency. Repeatability of cortisol and escape latency was increased and repeatability of struggle docility tended to be higher (approaching significance) in treated individuals. Increased repeatability was mainly caused by an increase of among-individual variance. Correlations among docility, escape latency and cortisol were stronger in treated animals compared to control animals. These results suggest that exposure to elevated levels of cortisol during adolescence can alter animal personality traits as well as behavioural syndromes. Social and risk-taking traits showed no correlation with cortisol levels and were unaffected by the experimental manipulation, indicating behavioural modularity. Taken together, our data highlight that cortisol can have organising effects during adolescence on the development of personality traits and behavioural syndromes, adding to the increasing evidence that not only early life but also adolescence is an important sensitive period for behavioural development.
Asunto(s)
Conducta Animal/efectos de los fármacos , Cobayas/fisiología , Hidrocortisona/farmacología , Maduración Sexual/efectos de los fármacos , Conducta Social , Estrés Fisiológico/efectos de los fármacos , Animales , Conducta Animal/fisiología , Conducta Exploratoria/efectos de los fármacos , Conducta Exploratoria/fisiología , Femenino , Glucocorticoides/metabolismo , Cobayas/crecimiento & desarrollo , Hidrocortisona/fisiología , Individualidad , Masculino , Fenotipo , Maduración Sexual/fisiología , Estrés Fisiológico/fisiología , SíndromeRESUMEN
Pericardial Effusion (PE) is a potentially life-threatening complication of Hematopoietic Cell Transplantation (HCT). Our study aim was to identify incidence, risk factors, response to treatment, and outcome of PE after pediatric HCT. All patients after HCT at our tertiary center between 2005 and 2010 were included. Endpoints were PE development and overall survival. We analyzed patient factors, HCT details, and complications and used Cox proportional hazard regression modeling to identify predictors for PE. Twelve out of 129 patients (9.3%) developed PE. Multivariate analysis demonstrated that young age at HCT was a predictor for PE: expressed per year increase in age HR = 0.66 (95% CI 0.46-0.95, p = 0.03). PE had no impact on overall mortality of HCT. Mild respiratory symptoms and vomiting were presenting symptoms for PE. Discontinuation of calcineurin inhibitors-with or without pericardiocentesis-was the only effective treatment for PE, in contrast to diuretics or increased immunosuppression. Seven of 12 PE patients had pericardiocentesis, which was safe and effective in all. Pericardial effusion is not rare after HCT, and young age is the only significant risk factor. Calcineurin inhibitor toxicity appears to be the primary cause of PE after HCT, and discontinuation is effective in the reduction of PE. Pericardiocentesis for PE is a safe and effective procedure. Pericardial effusion did not have an impact on survival after HCT.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Derrame Pericárdico/epidemiología , Adolescente , Inhibidores de la Calcineurina/efectos adversos , Niño , Preescolar , Diuréticos/uso terapéutico , Ecocardiografía , Femenino , Humanos , Inmunosupresores/uso terapéutico , Incidencia , Lactante , Masculino , Derrame Pericárdico/etiología , Derrame Pericárdico/terapia , Pericardiocentesis/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: Assessing a diverse biomarker panel (NT-proBNP, TNF-α, galectin-3, IL-6, Troponin I, ST2 and sFlt-1) to detect subclinical cardiotoxicity after treatment with anthracyclines. METHODS: Of 55 breast cancer patients biomarkers were assessed and echocardiography was performed one year after treatment with anthracyclines. RESULTS: 29.1% of patients showed abnormal biomarker levels: NT-proBNP in 18.2%, TNF-α and Galectin-3 in 7.3%. IL-6, troponin I, ST2 and sFlt-1 were normal in all patients. A correlation between left ventricular ejection fraction (LVEF) and NT-proBNP was observed (r = -0.564, p ≤ 0.01). CONCLUSION: The evaluated biomarkers do not contribute to early detection. Future research should focus on NT-proBNP.
Asunto(s)
Antineoplásicos/efectos adversos , Biomarcadores/sangre , Cardiotoxicidad/sangre , Galectina 3/sangre , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Factor de Necrosis Tumoral alfa/sangre , Adolescente , Adulto , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Cardiotoxicidad/diagnóstico , Cardiotoxicidad/etiología , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/diagnóstico , Ciclofosfamida/efectos adversos , Docetaxel , Doxorrubicina/efectos adversos , Ecocardiografía , Electroencefalografía , Ensayo de Inmunoadsorción Enzimática , Femenino , Corazón/efectos de los fármacos , Corazón/fisiopatología , Humanos , Persona de Mediana Edad , Sensibilidad y Especificidad , Taxoides/efectos adversos , Adulto JovenRESUMEN
BACKGROUND: Topotecan has been variably incorporated in the treatment of patients with relapsed Wilms tumour (WT) who failed initial treatment with three or more effective drugs. Our objective was to describe outcome and to retrospectively investigate the potential role of topotecan in relapsed WT patients. METHODS: Children who were treated with topotecan as part of their chemotherapeutic regimens for relapsed WT were identified and included in our retrospective study. Patient charts were reviewed for general patient characteristics, histology and stage at initial diagnosis, number and type of relapse, salvage treatment schedules, toxicity, response to treatment and outcome. RESULTS: From 2000 to 2012, 30 children (median age at relapse 5.5 years, range 1.6-14.5 years) were identified to have received topotecan as part of their salvage regimens (primary progressive disease n = 3, first, second and third relapse n = 13, 9 and 2 respectively, partial response n = 3). Topotecan was administered as a single agent (12 patients) or in combination with other drugs (18 patients). Sixteen patients had high-risk histology according to the SIOP classification, 15 died within 12 months because of progressive disease. Fourteen patients had SIOP intermediate-risk histology of which four patients displayed objective responses to topotecan. Overall, 6 out of 14 intermediate-risk patients survived (median follow up of 6 years), however, three of whom (stage V) had bilateral nephrectomy after topotecan treatment. CONCLUSIONS: Topotecan does not seem to show effectiveness in the treatment of relapsed WT patients with initial high-risk histology. In patients with intermediate-risk histology, the role of topotecan might deserve further attention, to prove its efficacy.
Asunto(s)
Neoplasias Renales , Recurrencia Local de Neoplasia , Topotecan/administración & dosificación , Adolescente , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Lactante , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Inhibidores de Topoisomerasa I , Tumor de Wilms/tratamiento farmacológico , Tumor de Wilms/mortalidad , Tumor de Wilms/patologíaRESUMEN
INTRODUCTION: Currently, very few guidelines for supportive care for children with cancer exist. In the Netherlands, nationwide guidelines are over 10 years old and mostly based on expert opinion. Consequently, there is growing support and need for clinical practice guidelines (CPGs), which ought to be developed with a well-defined methodology and include a systematic search of literature, evidence summaries, and a transparent description of the decision process for the final recommendations. Development of CPGs is time consuming; therefore, it is important to prioritize topics for which there is the greatest clinical demand. OBJECTIVES: This study aims to prioritize childhood cancer supportive care topics for development of CPGs. METHODS: A Delphi survey consisting of two rounds was conducted to prioritize relevant childhood cancer supportive care topics for the development of CPGs. A group of experts comprising 15 pediatric oncologists, 15 pediatric oncology nurses, and 15 general pediatricians involved in care for childhood cancer patients were invited to participate. All relevant supportive care topics in childhood cancer were rated. RESULTS: In both rounds, 36 panellists (82%) responded. Agreement between panellists was very good, with an intraclass correlation coefficient of 0.918 (95% confidence interval (CI) = 0.849-0.966, p < 0.001) in round 2. The ten topics with the highest score in the final round were infection, sepsis, febrile neutropenia, pain, nausea/vomiting, restrictions in daily life and activities, palliative care, procedural sedation, terminal care, and oral mucositis. CONCLUSION: We successfully used a Delphi survey to prioritize childhood cancer supportive care topics for the development of CPGs. This is a first step towards uniform and evidence-based Dutch guidelines in supportive care in childhood cancer. Even though performed nationally, we believe that this study can also be regarded as an example starting point for international development of CPGs in the field of supportive care in cancer or any other field for that matter.
Asunto(s)
Técnica Delphi , Oncología Médica/normas , Neoplasias/terapia , Cuidados Paliativos/normas , Pediatría/normas , Guías de Práctica Clínica como Asunto , Niño , Necesidades y Demandas de Servicios de Salud , Humanos , Oncología Médica/métodos , Países Bajos , Cuidados Paliativos/métodos , Pediatría/métodosRESUMEN
A 17-month-old girl with no medical history presented at our emergency room with abnormal vaginal bleeding and vaginal tissue loss with a "grape bunch" appearance. Physical examination showed no abnormalities, but gynaecological examination showed abnormal vaginal tissue protruding through the vagina introitus. Given the typical clinical presentation, the age of the girl and the location and aspect of the lesion, there was a high suspicion of the botryoid variant of embryonal rhabdomyosarcoma of the vagina. Histology of a biopsy of the lesion was consistent with embryonal rhabdomyosarcoma. As no metastases were detected, the girl received chemotherapy. This case report describes the importance of early recognition of the typical clinical symptoms of sarcoma botryoides, since a rapid diagnosis followed by treatment is necessary to prevent death.
Asunto(s)
Rabdomiosarcoma Embrionario/diagnóstico , Vagina/patología , Neoplasias Vaginales/diagnóstico , Biopsia , Femenino , Humanos , Lactante , Rabdomiosarcoma Embrionario/patología , Neoplasias Vaginales/patologíaRESUMEN
AIM: Cardiac 123I metaiodobenzylguanidine (MIBG) imaging can be influenced by several factors. We evaluated the relationship between catecholamine measurements and cardiac 123I MIBG uptake in neuroblastoma patients. PATIENTS, METHODS: 30 neuroblastoma patients were retrospectively assessed on cardiac 123I MIBG uptake and urinary catecholamine dopamine and metabolites, homovanillic acid (HVA) and vanillylmandelic acid (VMA). Cardiac 123I MIBG uptake was quantified by heart-to-mediastinum (H/M) ratios, which were calculated into standard deviation scores (SDS) using age-specific reference values. RESULTS: In 17 (57%) and 12 patients (40%) H/M ratio measurements were below -1.0 and -2.0 SDS at diagnosis. A significant inverse correlation between the average of urine metabolites HVA and VMA, and H/M ratio SDS was observed (r -.39, p = 0.04). Furthermore, there was a significant correlation between the urinary catecholamine metabolite HVA and H/M ratio SDS (r -.40, p=0.04). CONCLUSION: Routine calculation of H/M ratios in 123I MIBG scintigrams of neuroblastoma patients is not helpful because it will not identify cardiac ventricular dysfunction in this patient category. A low H/M ratio on 123I MIBG scintigraphy is explained by increased cathecholamine levels secreted by neuroblastoma tumours.
Asunto(s)
3-Yodobencilguanidina/farmacocinética , Catecolaminas/metabolismo , Corazón/diagnóstico por imagen , Miocardio/metabolismo , Neuroblastoma/diagnóstico por imagen , Neuroblastoma/metabolismo , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Cintigrafía , Radiofármacos/farmacocinética , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
It has been hypothesized that cerebral lateralization of function enhances cognitive performance. Evidence was found in birds and fish. However, recent research in humans did not support this hypothesis. We aimed to replicate and extend these findings for single- and dual-task performance in an ecologically relevant task. We combined a word generation task which is assumed to be primarily processed in the left hemisphere with a driving task which is assumed to be primarily processed in the right hemisphere. For each task the individual strength and direction of hemispheric lateralization was assessed by using functional transcranial Doppler sonography (fTCD). For each subject (36 right-handed, 35 nonright-handed) performance was measured in the two single-tasks and in the dual-task condition. On average, subjects showed a left hemisphere bias for the word generation task, a right hemisphere bias for the driving task and dual-task interference. Within subjects, lateralization of language and driving were statistically independent. In accordance with earlier studies, the results show no indication of a positive effect of strength of lateralization on performance in single-tasks or dual-task efficiency. We also found no advantage of a typical compared to an atypical or a contralateral compared to an ipsilateral lateralization pattern. In right-handers, but not in nonright-handers, we even found a negative relationship between strength of lateralization and dual-task efficiency for atypically lateralized subjects. This further supports the suggestion that lateralization does not enhance cognitive performance in humans.
Asunto(s)
Atención/fisiología , Conducción de Automóvil/psicología , Lateralidad Funcional/fisiología , Desempeño Psicomotor/fisiología , Conducta Verbal/fisiología , Mapeo Encefálico , Femenino , Humanos , Masculino , Enmascaramiento Perceptual , Solución de Problemas/fisiología , Valores de Referencia , Ultrasonografía Doppler Transcraneal , Adulto JovenRESUMEN
It has been hypothesized that functional cerebral lateralization enhances cognitive performance. Evidence was found in birds and fish. Our study aimed to test this hypothesis by analyzing the relationship between cerebral lateralization and both single-task performance and dual-task efficiency in humans. We combined a dynamic Landmark task which is assumed to be primarily processed in the right hemisphere and a frequently used word generation task which is assumed to be primarily processed in the left hemisphere. For each task individual strength and direction of hemispheric lateralization was assessed using functional transcranial Doppler sonography (fTCD). For each subject (15 women, 11 men), performance was measured in the two single-tasks and in the dual-task condition. Performance was not related to strength or direction of lateralization in single-tasks. With regard to dual-task efficiency, we found the expected advantage of having a typical lateralization pattern. Moreover, the results showed a slight negative, rather than a positive, relationship between strength of lateralization and dual-task efficiency. Further analysis showed that this negative relationship may only be present in subjects showing non-significant lateralization for one or both tasks. Therefore, the hypothesis that cerebral lateralization enhances human cognitive performance is too general: having two functions significantly lateralized to different hemispheres enhances dual-task efficiency, in this group strength of lateralized does not matter. However, if one or both functions are not significantly lateralized overall performance is worse and in this group, performance is negatively related to increased strength of lateralization.
Asunto(s)
Mapeo Encefálico , Encéfalo/irrigación sanguínea , Encéfalo/fisiología , Circulación Cerebrovascular/fisiología , Lateralidad Funcional/fisiología , Ultrasonografía Doppler Transcraneal , Femenino , Humanos , Lenguaje , Masculino , Pruebas Neuropsicológicas , Conducta Espacial/fisiología , Estadística como Asunto , Ultrasonografía Doppler , Vocabulario , Adulto JovenRESUMEN
Brain lateralization refers to the division of labour between the two hemispheres in controlling a wide array of functions and is remarkably well developed in humans. Based on sex differences in lateralization of handedness and language, several hypotheses have postulated an effect of prenatal exposure to testosterone on human lateralization development, the topic of a long-standing and unresolved debate. Here we demonstrate a clear relationship between prenatal levels of testosterone as assessed from amniotic fluid of healthy pregnant mothers and language lateralization of their offspring at the age of 6 years. Using focused attention conditions in the dichotic listening task, in which the child is instructed to report information from the left ear or the right ear, we were able to differentiate between potential effects of early testosterone on the left hemisphere and effects on inter-hemispheric connectivity. This provides a new method to distinguish between the claims of the different hypotheses. The results suggest that in girls higher prenatal testosterone exposure facilitates left hemisphere language processing, whereas in boys it reduces the information transfer via the corpus callosum.
Asunto(s)
Lateralidad Funcional/fisiología , Lenguaje , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Caracteres Sexuales , Testosterona/efectos adversos , Líquido Amniótico/metabolismo , Audiometría/métodos , Niño , Preescolar , Pruebas de Audición Dicótica/métodos , Femenino , Humanos , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/diagnóstico , Efectos Tardíos de la Exposición Prenatal/metabolismo , Radioinmunoensayo/métodos , Tiempo de Reacción/fisiología , Estadística como Asunto , Testosterona/metabolismoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Rabdomiosarcoma/terapia , Niño , Terapia Combinada , Femenino , Humanos , Metástasis de la Neoplasia , Inducción de Remisión , Rabdomiosarcoma/tratamiento farmacológico , Rabdomiosarcoma/patología , Rabdomiosarcoma/cirugía , Acondicionamiento PretrasplanteRESUMEN
BACKGROUND: As endovascular stents are altered to add functionality, eg, by adding radiopaque coatings, biocompatibility may suffer. METHODS AND RESULTS: We examined the vascular response in porcine coronary arteries to stainless steel gold-coated NIR stents (7-cell, Medinol, Inc). Stents, 9 and 16 mm in length, were left bare or coated with a 7-microm layer of gold. Physical and material effects were examined in four different gold-coated stent types, two at each length that either had the coating applied to the standard strut, ie, gold coated thicker than controls, or had the coating applied to thinned struts, ie, gold coated of the same thickness as control struts. Simple gold coating exacerbated intimal hyperplastic and inflammatory reactions over 28 days, but postplating thermal processing smoothed the coating surface and negated the adverse tissue response to gold. The relative amounts of base steel and gold coating and their resistances to expansion and collapse determined the extent of stent recoil. CONCLUSIONS: Gold coatings enhance the radiopacity of steel stents, but not without effects on vascular repair. Material effects predominate and can be abrogated by heating coated stents to alter surface finish and material purity. Clinical results may suffer unless consideration is given to material and physical effects of gold.
Asunto(s)
Vasos Coronarios/efectos de los fármacos , Oro/toxicidad , Stents , Animales , Vasos Coronarios/patología , Calor , Hiperplasia/patología , Inflamación/patología , Acero Inoxidable , Propiedades de Superficie , PorcinosRESUMEN
OBJECTIVES: The purpose of this study was to determine long-term effects of stent-based paclitaxel delivery on amount, rate and composition of neointimal thickening after stent implantation. BACKGROUND: Paclitaxel prevents vascular smooth muscle cell proliferation and migration in vitro and in vivo. These actions, coupled with low solubility, make it a viable candidate for modulating vascular responses to injury and prolonged effects after local delivery. We asked whether local delivery of paclitaxel for a period of weeks from a stent coated with a bioerodible polymer could produce a sustained reduction in neointimal hyperplasia for up to six months after stenting. METHODS: Stainless steel stents were implanted in the iliac arteries of rabbits after endothelial denudation. Stents were uncoated or coated with a thin layer of poly(lactide-co-sigma-caprolactone) copolymer alone or containing paclitaxel, 200 microg. RESULTS: Paclitaxel release in vitro followed first-order kinetics for two months. Tissue responses were examined 7, 28, 56 or 180 days after implantation. Paclitaxel reduced intimal and medial cell proliferation three-fold seven days after stenting and virtually eliminated later intimal thickening. Six months after stenting, long after drug release and polymer degradation were likely complete, neointimal area was two-fold lower in paclitaxel-releasing stents. Tissue responses in paclitaxel-treated vessels included incomplete healing, few smooth muscle cells, late persistence of macrophages and dense fibrin with little collagen. CONCLUSIONS: Poly(lactide-co-sigma-caprolactone) copolymer-coated stents permit sustained paclitaxel delivery in a manner that virtually abolishes neointimal hyperplasia for months after stent implantation, long after likely completion of drug delivery and polymer degradation.
Asunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Enfermedad Coronaria/prevención & control , Sistemas de Liberación de Medicamentos , Paclitaxel/administración & dosificación , Stents , Túnica Íntima/patología , Animales , Enfermedad Coronaria/patología , Conejos , Recurrencia , Factores de Tiempo , Túnica Íntima/efectos de los fármacosRESUMEN
Intraventricular haemorrhages (IVH) are the most commonly occurring intracranial haemorrhages in neonates, especially in preterm infants. The origin of IVHs is located in the germinal matrix. The cause of an IVH is a combination of intravascular, vascular and extravascular factors. The diagnosis is made by ultrasound. Knowledge on the causes of antenatal haemorrhages lags far behind knowledge on the causes of postnatal haemorrhages. In cases of haemodynamic changes in utero, ultrasound could be useful to examine the foetal brain. The presence of an intracranial haemorrhage in utero greatly influences the prognosis of the infant.
Asunto(s)
Enfermedades Fetales/diagnóstico por imagen , Hemorragias Intracraneales/diagnóstico por imagen , Adulto , Femenino , Enfermedades Fetales/etiología , Humanos , Hemorragias Intracraneales/etiología , Embarazo , Ultrasonografía PrenatalRESUMEN
The quality of general movements (GMs) was assessed repeatedly during the first postnatal months in a mixed group of 52 children at either low or high risk for neurodevelopmental disorders. In addition, all children were reexamined at 4 to 9 years. The follow-up assessment consisted of a neurological examination and an evaluation of behaviour by means of parental questionnaires. The quality of GMs changed frequently, to stabilize in the final phase. The final GM phase is that of the so-called fidgety GMs which occurs between 2 and 4 months postterm. The quality of the fidgety GMs predicted outcome very well. Definitely abnormal GMs were associated with a high risk for the development of cerebral palsy, whereas mildly abnormal GMs were associated with the development of minor neurological dysfunction, attention-deficit-hyperactivity disorder, and aggressive behaviour.