A closer look at discordant placental echogenicity: two cases under the microscope.

Discordant placental echogenicity is observed in MC pregnancies complicated with twin anemia-polycythemia sequence, but could also belong to complicated singleton gestation.

Fetal pancreatic Langerhans islets size in pregnancies with metabolic disorders.

Objective: Metabolic disorders are a pandemic and increasing health problem. Women of childbearing age may also be affected, thus an abnormal metabolism may interfere with pregnancy short- and long-term outcomes, harming both mother and child. In the context of an abnormal maternal and intrauterine metabolic milieu the development of fetal organs, including pancreas, may be affected. Aim: To investigate the effects of pregnancy metabolic disorders on the morphology of pancreatic Langerhans islets in human late-third trimester stillborn fetuses. Methods: Samples from fetal pancreas underwent a quantitative histological evaluation to detect differences between pregnancy with (cases, n = 9) or without (controls, n = 6) abnormal metabolism. Results: Results show that the islets size increases in fetuses from dysmetabolic pregnancies and that this increment is related to both beta-cell hyperplasia and hypertrophy. Moreover, according to pregnancy and fetal metabolic disorders, a threshold of abnormal size of the islets has been identified. Above this threshold the size of fetal pancreatic Langerhans islets should be considered excessively increased. Conclusion: The study suggests that an accurate fetal pancreas analysis supplies an important tool in stillborn fetus, to discover metabolic disturbances that should be kept in mind and managed in future pregnancies.

Dynamic and Cell-Specific DACH1 Expression in Human Neocortical and Striatal Development.

DACH1 is the human homolog of the Drosophila dachshund gene, which is involved in the development of the eye, nervous system, and limbs in the fly. Here, we systematically investigate DACH1 expression patterns during human neurodevelopment, from 5 to 21 postconceptional weeks. By immunodetection analysis, we found that DACH1 is highly expressed in the proliferating neuroprogenitors of the developing cortical ventricular and subventricular regions, while it is absent in the more differentiated cortical plate. Single-cell global transcriptional analysis revealed that DACH1 is specifically enriched in neuroepithelial and ventricular radial glia cells of the developing human neocortex. Moreover, we describe a previously unreported DACH1 expression in the human striatum, in particular in the striatal medium spiny neurons. This finding qualifies DACH1 as a new striatal projection neuron marker, together with PPP1R1B, BCL11B, and EBF1. We finally compared DACH1 expression profile in human and mouse forebrain, where we observed spatio-temporal similarities in its expression pattern thus providing a precise developmental description of DACH1 in the 2 mammalian species.

Integrating molecular and structural findings: Wnt as a possible actor in shaping cognitive impairment in Cornelia de Lange syndrome.

Cornelia de Lange Syndrome (CdLS) is a choesinopathy: a severe genetic disorder caused by mutations in the cohesin complex genes. The phenotype is characterized by typical facial dysmorphism, growth impairment and multiorgan abnormalities including brain alterations. Wnt pathway is known to play a fundamental role in central nervous system development and it has been shown that Wnt pathway is disrupted in CdLS animal models and patients cells. In this review we investigate the possible link between Wnt pathway disruption and brain abnormalities in Cornelia de Lange Syndrome as such molecular impairment could lead to an abnormal embryonic development resulting in brain abnormalities (i.e. microcephaly, cerebellar hypoplasia, abnormal cortical development) in patients with Cornelia de Lange Syndrome.

M1 and M2 macrophages' clinicopathological significance in cutaneous melanoma.

Skin malignant melanoma (MM) is an aggressive cancer with an increasing incidence with limited therapies in advanced stages. Tumor-associated macrophages (TAMs) are the major immune constituent of the MM microenvironment and contribute toward its prognosis. TAMs' characterization and localization in human cancer is important to understand cancer progression and to identify molecular personalized therapies. M2 TAMs in stage I-II MMs are associated with worse prognostic parameters. A comprehensive M1-macrophage and M2-macrophage intratumoral localization and quantification in all stages of skin MMs is documented here with its clinical significance. To highlight immune pathways and possible early indicators of MM progression, we evaluated the number of M1 and M2 TAMs and intratumoral distribution in a large series of skin MMs. CD68 double immunostaining with MRP8-14 or inducible nitric oxide synthase (M1 macrophages) and with CD163 or CD204 (M2 macrophages) was performed in 94 stage I-IV skin MMs with a long duration of follow-up. The accumulation and distribution of M1 and M2 TAMs in intratumoral nests, stroma, and at the invasive front was correlated with clinicopathological variables. Since the early stage of MMs, M1 intratumoral macrophages were fewer than the M2 population; their recruitment was rapidly and progressively overwhelmed by an increase in M2 TAMs during MM progression. Independent of their intratumoral distribution, the accumulation of both M1 and M2 TAMs is associated with poor prognostic indicators and patients' survival. M1-recruited macrophages shift to the M2 phenotype early in MM development, possibly induced by high inducible nitric oxide synthase intratumoral increase peculiarly occurring since the initial MM stages. M2-recruited TAMs overwhelm M1 accumulation in all stages of MM progression, thus favoring neoplastic growth and dissemination. Independent of their intratumoral distribution, the prevalent accumulation of M2 TAMs in MM is statistically confirmed to be a poor indicator of patients' outcome and a potential target of immune therapies.

Molecular and functional definition of the developing human striatum.

The complexity of the human brain derives from the intricate interplay of molecular instructions during development. Here we systematically investigated gene expression changes in the prenatal human striatum and cerebral cortex during development from post-conception weeks 2 to 20. We identified tissue-specific gene coexpression networks, differentially expressed genes and a minimal set of bimodal genes, including those encoding transcription factors, that distinguished striatal from neocortical identities. Unexpected differences from mouse striatal development were discovered. We monitored 36 determinants at the protein level, revealing regional domains of expression and their refinement, during striatal development. We electrophysiologically profiled human striatal neurons differentiated in vitro and determined their refined molecular and functional properties. These results provide a resource and opportunity to gain global understanding of how transcriptional and functional processes converge to specify human striatal and neocortical neurons during development.

An imbalance of COX level is not related to placental abruption.

AIMS: Muscularised basal plate arteries (MA) or chorioamnionitis (CA) are often present in placental abruption. The aim of this study was to evaluate the placental expression of COX 1 and COX 2 in cases of placental abruption with MA or CA hypothesising that an imbalance in COX placental expression might be implicated in its pathogenesis. METHODS: COX 1 and COX 2 placental immunostaining was analysed in 16 placentas with abruption (nine with MA, seven with CA), in 26 normal placentas and in 10 gestational age-matched MA or CA cases without abruption. RESULTS: COX 1 and COX 2 protein expression was observed in all cases, both in placental abruption and in normal placentas. No differences in distribution of immunoreactivity were observed either between cases and controls or between MA and CA. The mean COX 1 ratio between COX-positive cells and all stromal cells was significantly lower in placental abruption with MA (0.14±0.05) when compared with cases with CA (0.35±0.06) and normal placenta (0.23±0.02; p<0.001). The mean COX 2 ratio was lower in placental abruption with MA than in normal placenta (0.09±0.06 vs 0.18±0.05: p<0.001). In contrast, no difference in COX 1 and COX 2 ratio was observed between MA cases with or without abruption and between CA cases with or without abruption. CONCLUSIONS: It is hypothesised that an imbalance of normal COX level may be present in cases with MA and CA but it is not related to placental abruption.