Intrauterine transfusion under fetal analgesia: the evaluation of perinatal outcomes

IntroductionIntrauterine transfusion is the treatment for fetal anemia resulting from maternal alloimmunization, infections (parvovirus B19 and cytomegalovirus), single demise of a monochorionic twin, chorioangioma, and other rare conditions. Fetal analgesia is mandatory to reduce movement and pain perception during the procedure. This study aims to evaluate perinatal outcomes for such procedures, following the routine use of fetal analgesia in our clinical practice.Materials and methodsRetrospective analysis of cases from 2009 to 2022, including all confirmed fetal anemia with fetal blood sampling. After fetal analgesia, Rh-negative concentrated red blood cells were transfused, with ultrasonographic follow-up 24 h and 1 week later. In case of suspected brain lesion, magnetic resonance imaging was performed. Elective delivery was considered in case of persistent anemia after 34 weeks. Post-natal follow-up and comprehensive obstetric and perinatal outcomes data were collected.ResultsAltogether 59 anemic fetuses were included, with 34 (57.6%) being hydropic. The causes of anemia were maternal alloimmunization (22, 37.3%), infections (13, 22%), monochorionicity (10, 16.9%), rare conditions (9, 15.3%), and two chorioangiomas (3.4%). The median gestational age at the procedure was 25.2 weeks (18–32 weeks), with no related preterm premature rupture of membranes (<48 h), or side effects from fetal analgesia. Gestational age at delivery was 33 weeks (26–41 weeks), with survival rate of 90%. There were four fetal demises, two termination of pregnancies, and eight neonatal deaths due to persistent severe anemia after preterm delivery. The main contributors to adverse outcome were the type of anemia, and the management with a preterm delivery.ConclusionIntrauterine transfusion of red blood cells under analgesia is safe, with low incidence of obstetric complication

A case of ultrasound diagnosis of fetal hiatal hernia in late third trimester of pregnancy

Congenital hiatal hernia is a condition characterized by herniation of the abdominal organs, most commonly the stomach, through a physiological but overlax esophageal hiatus into the thoracic cavity. Prenatal diagnosis of this anomaly is unusual and only eight cases have been reported in the literature. In this paper we describe a case of congenital hiatal hernia that was suspected at ultrasound at 39 weeks' gestation, on the basis of a cystic mass in the posterior mediastinum, juxtaposed to the vertebral body. Postnatal upper gastrointestinal tract series confirmed the prenatal diagnosis. Postnatal management was planned with no urgency. Hiatal hernia is not commonly considered in the differential diagnosis of fetal cystic chest anomalies. This rare case documents the importance of prenatal diagnosis of this anomaly for prenatal counseling and postnatal management

Insolita causa di addome acuto in paziente adulto: l’ileo biliare

L’ileo biliare è una condizione morbosa rara descritta tra le complicanze della litiasi della colecisti. È causa dell’1-3% delle ostruzioni meccaniche del piccolo intestino. Interessa più frequentemente pazienti di età compresa tra 63 e 85 anni. La diagnosi pre-operatoria è generalmente posta con ritardo variabile da 1 a 10 giorni per l’assenza di una sintomatologia specifica. Caso clinico. Gli Autori riportano il caso di un uomo di 50 anni in cui è stata posta diagnosi di occlusione meccanica del piccolo intestino da voluminosa concrezione litiasica. L’occlusione ileale è stata dimostrata con la TC. Il paziente è stato sottoposto in urgenza ad intervento chirurgico, in un unico tempo, di enterolitotomia, colecistectomia e riparazione della fistola duodenale. Il decorso clinico è stato regolare e il paziente è stato dimesso in XIV giornata. Discussione. Nel nostro caso la diagnosi di ileo biliare è stata posta con un ritardo di 5 giorni. L’ecotomografia del fegato e delle vie biliari non è stata in grado di visualizzare la colecisti. La diagnosi è stata posta con la TC che si conferma gold standard diagnostico. Conclusioni. Lo stato clinico del paziente influenza la strategia chirurgica. Nel nostro paziente, considerato a basso rischio, è stato possibile l’intervento chirurgico in un unico tempo. La procedura in due tempi, enterolitotomia e successiva colecistectomia con riparazione della fistola, va riservata ai pazienti ad alto rischio

PFOA and PFOS Disrupt the Generation of Human Pancreatic Progenitor Cells

The two most infamous perfluoroalkyl acids, PFOA and PFOS, are persistent, widespread, bioaccumulative, and associated with many health issues. However, knowledge about their potential toxicity to the developing pancreas or their association with metabolic diseases, such as diabetes, in humans is limited. In this study, we investigated the effects of PFOA and PFOS on the <i>in vitro</i> generation of pancreatic progenitor cells from human embryonic stem cells, a process that mimics <i>in vivo</i> organogenesis. We demonstrated for the first time that these two pollutants significantly affect the early stages of human pancreatic progenitor cell specification, even at very low environmentally and human-relevant doses. Thus, our findings further emphasize the substantial health risks associated with prenatal exposure to PFOA and PFOS

PFOA and PFOS Disrupt the Generation of Human Pancreatic Progenitor Cells

The two most infamous perfluoroalkyl acids, PFOA and PFOS, are persistent, widespread, bioaccumulative, and associated with many health issues. However, knowledge about their potential toxicity to the developing pancreas or their association with metabolic diseases, such as diabetes, in humans is limited. In this study, we investigated the effects of PFOA and PFOS on the <i>in vitro</i> generation of pancreatic progenitor cells from human embryonic stem cells, a process that mimics <i>in vivo</i> organogenesis. We demonstrated for the first time that these two pollutants significantly affect the early stages of human pancreatic progenitor cell specification, even at very low environmentally and human-relevant doses. Thus, our findings further emphasize the substantial health risks associated with prenatal exposure to PFOA and PFOS

STAGA Recruits Mediator to the MYC Oncoprotein To Stimulate Transcription and Cell Proliferation▿

Activation of eukaryotic gene transcription involves the recruitment by DNA-binding activators of multiprotein histone acetyltransferase (HAT) and Mediator complexes. How these coactivator complexes functionally cooperate and the roles of the different subunits/modules remain unclear. Here we report physical interactions between the human HAT complex STAGA (SPT3-TAF9-GCN5-acetylase) and a “core” form of the Mediator complex during transcription activation by the MYC oncoprotein. Knockdown of the STAF65γ component of STAGA in human cells prevents the stable association of TRRAP and GCN5 with the SPT3 and TAF9 subunits; impairs transcription of MYC-dependent genes, including MYC transactivation of the telomerase reverse transcriptase (TERT) promoter; and inhibits proliferation of MYC-dependent cells. STAF65γ is required for SPT3/STAGA interaction with core Mediator and for MYC recruitment of SPT3, TAF9, and core Mediator components to the TERT promoter but is dispensable for MYC recruitment of TRRAP, GCN5, and p300 and for acetylation of nucleosomes and loading of TFIID and RNA polymerase II on the promoter. These results suggest a novel STAF65γ-dependent function of STAGA-type complexes in cell proliferation and transcription activation by MYC postloading of TFIID and RNA polymerase II that involves direct recruitment of core Mediator

Coating with spermine-pullulan polymer enhances adenoviral transduction of mesenchymal stem cells

Mesenchymal stem cells (MSCs) are adult stem cells with multilineage potential, which makes them attractive tools for regenerative medicine applications. Efficient gene transfer into MSCs is essential not only for basic research in developmental biology but also for therapeutic applications involving gene-modification in regenerative medicine. Adenovirus vectors (Advs) can efficiently and transiently introduce an exogenous gene into many cell types via their primary receptors, the coxsackievirus and adenovirus receptors, but not into MSCs, which are deficient in coxsackievirus and adenovirus receptors expression. To overcome this problem, we developed an Adv coated with a spermine-pullulan (SP) cationic polymer and investigated its physicochemical properties and internalization mechanisms. We demonstrated that the SP coating could enhance adenoviral transduction of MSCs without detectable cytotoxicity or effects on differentiation. Our results argue in favor of the potentiality of the SP-coated Adv as a prototype vector for efficient and safe transduction of MSCs

Cavernous hemangioma of the parietal bone. Case report and review of the literature

Intraosseous cavernous hemangiomas are a rare finding in the calvarium. It is a benign tumor arising from the intrinsic vasculature of the bone. We report one case observed in a 20 year-old male. The diagnostic peculiarities and therapeutic implications of this lesion are discussed and the available literature on this subject is reviewed. These tumors do not recur once a radical surgical removal is performed

MYC interacts with the human STAGA coactivator complex via multivalent contacts with the GCN5 and TRRAP subunits.

MYC is an oncogenic DNA-binding transcription activator of many genes and is often upregulated in human cancers. MYC has an N-terminal transcription activation domain (TAD) that is also required for cell transformation. Various MYC TAD-interacting coactivators have been identified, including the transcription/transformation-associated protein (TRRAP), a subunit of different histone acetyltransferase (HAT) complexes such as the human "SPT3-TAF9-GCN5 Acetyltransferase" (STAGA) complex involved in MYC transactivation of the TERT gene. However, it remains unclear whether TRRAP and/or other subunits are directly contacted by MYC within these macromolecular complexes. Here, we characterize the interactions of MYC TAD with the STAGA complex. By protein crosslinking we identify both TRRAP and the GCN5 acetyltransferase as MYC TAD-interacting subunits within native STAGA. We show that purified GCN5 binds to an N-terminal sub-domain of MYC TAD (residues 21-108) and that the interaction of GCN5 and STAGA with this sub-domain is dependent on two related sequence motifs: M2 within the conserved MYC homology box I (MBI), and M3 located between residues 100-106. Interestingly, specific substitutions within the M2/3 motifs that only moderately reduce the intracellular MYC-STAGA interaction and do not influence dimerization of MYC with its DNA-binding partner MAX, strongly inhibit MYC acetylation by GCN5 and reduce MYC binding and transactivation of the GCN5-dependent TERT promoter in vivo. Hence, we propose that MYC associates with STAGA through extended interactions of the TAD with both TRRAP and GCN5 and that the TAD-GCN5 interaction is important for MYC acetylation and MYC binding to certain chromatin loci