Pregnancy induces a number of immunological, hormonal, and metabolic changes that are necessary for the mother to adapt her body to this new physiological situation. The microbiome of the mother, the placenta and the fetus influence the fetus growth and undoubtedly plays a major role in the adequate development of the newborn infant. Hence, the microbiome modulates the inflammatory mechanisms related to physiological and pathological processes that are involved in the perinatal progress through different mechanisms. The present review summarizes the actual knowledge related to physiological changes in the microbiota occurring in the mother, the fetus, and the child, both during neonatal period and beyond. In addition, we approach some specific pathological situations during the perinatal periods, as well as the influence of the type of delivery and feeding.

Fetal alcohol spectrum disorder is the main preventable cause of intellectual disability in the Western world. Although binge drinking is the most studied prenatal alcohol exposure pattern, other types of exposure, such as the Mediterranean, are common in specific geographic areas. In this study, we analyze the effects of prenatal alcohol exposure in binge and Mediterranean human drinking patterns on placenta and brain development in C57BL/6J mice. We also assess the impact of prenatal treatment with the epigallocatechin-3-gallate antioxidant in both groups. Study experimental groups for Mediterranean or binge patterns: (1) control; (2) ethanol; (3) ethanol + epigallocatechin-3-gallate. Brain and placental tissue were collected on gestational Day 19. The molecular pathways studied were fetal and placental growth, placental angiogenesis (VEGF-A, PLGF, VEGF-R), oxidative stress (Nrf2), and neurodevelopmental processes including maturation (NeuN, DCX), differentiation (GFAP) and neural plasticity (BDNF). Prenatal alcohol exposure resulted in fetal growth restriction and produced imbalances of placental angiogenic factors. Moreover, prenatal alcohol exposure increased oxidative stress and caused significant alterations in neuronal maturation and astrocyte differentiation. Epigallocatechin-3-gallate therapy ameliorated fetal growth restriction, attenuated alcohol-induced changes in placental angiogenic factors, and partially rescued neuronal nuclear antigen (NeuN), (doublecortin) DCX, and (glial fibrillary acidic protein) GFAP levels. Any alcohol consumption (Mediterranean or binge) during pregnancy may generate a fetal alcohol spectrum disorder phenotype and the consequences may be partially attenuated by a prenatal treatment with epigallocatechin-3-gallate.

Tagging of RNases, such as the ribotoxin α-sarcin, with the variable domains of antibodies directed to surface antigens that are selectively expressed on tumor cells endows cellular specificity to their cytotoxic action. A recombinant single-chain immunotoxin based on the ribotoxin α-sarcin (IMTXA33αS), produced in the generally regarded as safe (GRAS) yeast Pichia pastoris, has been recently described as a promising candidate for the treatment of colorectal cancer cells expressing the glycoprotein A33 (GPA33) antigen, due to its high specific and effective cytotoxic effect on in vitro assays against targeted cells. Here we report the in vivo antitumor effectiveness of this immunotoxin on nude mice bearing GPA33-positive human colon cancer xenografts. Two sets of independent assays were performed, including three experimental groups: control (PBS) and treatment with two different doses of immunotoxin (50 or 100 μg/ injection) (n = 8). Intraperitoneal administration of IMTXA33αS resulted in significant dose-dependent tumor growth inhibition. In addition, the remaining tumors excised from immunotoxin-treated mice showed absence of the GPA33 antigen and a clear inhibition of angiogenesis and proliferative capacity. No signs of immunotoxin-induced pathological changes were observed from specimens tissues. Overall these results show efficient and selective cytotoxic action on tumor xenografts, combined with the lack of severe side effects, suggesting that IMTXA33αS is a potential therapeutic agent against colorectal cancer.

Neuroblastoma causes 15% of cancer mortality in children. High risk neuroblastoma has poor prognosis, with high relapse rate and mortality despite multimodal treatment. 123-I-meta-iodo-benzyl-guanidine (mIBG) scintigraphy is one of the current standard diagnostic procedures in neuroblastoma. mIBG can also be used therapeutically, labeled with 131-I, as a radiopharmaceutical agent, delivering targeted radiotherapy to tumoral sites. But published data of this strategy show heterogeneous results. One concern is that in most reports the infused activity is only based in body-weight, which could lead to infra or over-treatment, depending on inter-patient variability in radiation absorption. Activity adjustment by whole-body dosimetry can be used to homogeneize the treatment. Also, mIBG avid tumors may lose avidness along the treatment. As mIBG is used both for treatment and response evaluation, this could result in undetected progressions in patients with apparent complete response. We present a retrospective single-center review of neuroblastoma patients who received therapeutic 131-I-mIBG, focusing on cases with dosimetry-adjusted activity. Dosimetry allowed for a more precise delivery of radiation, reducing 81.1% of deviation from absorption target of 4 Gray (Gy), from 23.4% (±0.936 Gy) to 4.4% (± 0.176 Gy). Patients who showed partial or complete response had better and longer survival. Relapse/progression in non-responders was an early event (within 3 months from treatment). We also present one case of progression with apparent complete response due to loss of mIBG avidness, detected in our series.

Background: The aim of this multicenter retrospective study and literature review was to review management and outcomes of neonatal esophageal perforation (NEP). Methods: Protocol data were collected from four European Centers on gestational age, factors surrounding feeding tube insertion, management and outcomes. Results: The 5-year study period (2014–2018) identified eight neonates with median gestational age of 26 + 4 weeks (23 + 4–39) and median birth weight 636 g (511–3500). All patients had NEP from enterogastric tube insertions, with the perforation occurring at median 1st day of life (range 0–25). Seven/eight patients were ventilated (two/seven-high frequency oscillation). NEP became apparent on first tube placement (n = 1), first change (n = 5), and after multiple changes (n = 2). Site of perforation was known in six (distal n = 3, proximal n = 2 and middle n = 1). Diagnosis was established by respiratory distress (n = 4), respiratory distress and sepsis (n = 2) and post-insertion chest X-ray (n = 2). Management in all patients included antibiotics and parenteral nutrition with two/eight receiving steroids and ranitidine, one/eight steroids only and one/eight ranitidine only. One neonate had a gastrostomy inserted, while in another an enterogastric tube was orally successfully re-inserted. Two neonates developed pleural effusion and/or mediastinal abscess requiring chest tube. Three neonates had significant morbidities (related to prematurity) and there was one death 10 days post-perforation (related to prematurity complications). Conclusions: NEP during NGT insertion is rare even in premature infants after evaluating data from four tertiary centers and reviewing the literature. In this small cohort, conservative management seems to be safe. A larger sample size will be necessary to answer questions on efficacy of antibiotics, antacids and NGT re-insertion time frame in NEP.