Clinical-haematological changes and predictors of severity in acute food protein-induced enterocolitis syndrome reactions at oral food challenge: a multicentre observational study.

BACKGROUND: Oral food challenge (OFC) is the gold standard for diagnosis of acute Food Protein-Induced Enterocolitis Syndrome (FPIES). No diagnostic/prognostic biomarkers are available, and OFC assessment criteria are not validated. OBJECTIVE: To assess clinical-haematological changes and predictors of severity of FPIES reactions at OFC. METHODS: Observational multicentre prospective study. Children aged 0-18 years diagnosed with acute FPIES were recruited at follow-up OFC in 12 tertiary centres in Spain and Italy. OFC Outcomes (as positive/negative/inconclusive and mild/moderate/severe) were assessed based on published '2017 FPIES Consensus' criteria. Clinical characteristics were recorded, and full blood count was done at baseline, reaction onset and 4 hours later. Regression analysis was performed to assess predictors of severe reactions at OFC. RESULTS: 81 children had positive OFC (mild in 11% (9/81), moderate in 61% (49/81), severe in 28% (23/81)). Increase in neutrophils and reduction in eosinophils, basophils and lymphocytes was observed (P-value<0.05). OFC was inconclusive in 19 cases despite objective signs or neutrophilia. Regression analysis showed a 2-day OFC protocol where only 25% of an age-appropriate portion is given on day 1 (not gender, age, culprit food, cumulative dose and previous reaction severity) was associated with reduced odds of severe reaction compared to giving multiple doses in a single day. CONCLUSION: Distinct haematological changes may help support FPIES diagnosis. Current OFC assessment criteria may not capture the broad spectrum of acute FPIES presentations. This 2-day protocol may associate a reduced risk of severe reactions. Future work should aim to develop safer OFC and non-OFC diagnostics for FPIES.

The Polycomb group (PcG) protein EZH2 supports the survival of PAX3-FOXO1 alveolar rhabdomyosarcoma by repressing FBXO32 (Atrogin1/MAFbx).

The Polycomb group (PcG) proteins regulate stem cell differentiation via the repression of gene transcription, and their deregulation has been widely implicated in cancer development. The PcG protein Enhancer of Zeste Homolog 2 (EZH2) works as a catalytic subunit of the Polycomb Repressive Complex 2 (PRC2) by methylating lysine 27 on histone H3 (H3K27me3), a hallmark of PRC2-mediated gene repression. In skeletal muscle progenitors, EZH2 prevents an unscheduled differentiation by repressing muscle-specific gene expression and is downregulated during the course of differentiation. In rhabdomyosarcoma (RMS), a pediatric soft-tissue sarcoma thought to arise from myogenic precursors, EZH2 is abnormally expressed and its downregulation in vitro leads to muscle-like differentiation of RMS cells of the embryonal variant. However, the role of EZH2 in the clinically aggressive subgroup of alveolar RMS, characterized by the expression of PAX3-FOXO1 oncoprotein, remains unknown. We show here that EZH2 depletion in these cells leads to programmed cell death. Transcriptional derepression of F-box protein 32 (FBXO32) (Atrogin1/MAFbx), a gene associated with muscle homeostasis, was evidenced in PAX3-FOXO1 RMS cells silenced for EZH2. This phenomenon was associated with reduced EZH2 occupancy and H3K27me3 levels at the FBXO32 promoter. Simultaneous knockdown of FBXO32 and EZH2 in PAX3-FOXO1 RMS cells impaired the pro-apoptotic response, whereas the overexpression of FBXO32 facilitated programmed cell death in EZH2-depleted cells. Pharmacological inhibition of EZH2 by either 3-Deazaneplanocin A or a catalytic EZH2 inhibitor mirrored the phenotypic and molecular effects of EZH2 knockdown in vitro and prevented tumor growth in vivo. Collectively, these results indicate that EZH2 is a key factor in the proliferation and survival of PAX3-FOXO1 alveolar RMS cells working, at least in part, by repressing FBXO32. They also suggest that the reducing activity of EZH2 could represent a novel adjuvant strategy to eradicate high-risk PAX3-FOXO1 alveolar RMS.

Proteomics boosts translational and clinical microbiology.

The application of proteomics to translational and clinical microbiology is one of the most advanced frontiers in the management and control of infectious diseases and in the understanding of complex microbial systems within human fluids and districts. This new approach aims at providing, by dedicated bioinformatic pipelines, a thorough description of pathogen proteomes and their interactions within the context of human host ecosystems, revolutionizing the vision of infectious diseases in biomedicine and approaching new viewpoints in both diagnostic and clinical management of the patient. Indeed, in the last few years, many laboratories have matured a series of advanced proteomic applications, aiming at providing individual proteome charts of pathogens, with respect to their morph and/or cell life stages, antimicrobial or antimycotic resistance profiling, epidemiological dispersion. Herein, we aim at reviewing the current state-of-the-art on proteomic protocols designed and set-up for translational and diagnostic microbiological purposes, from axenic pathogens' characterization to microbiota ecosystems' full description. The final goal is to describe applications of the most common MALDI-TOF MS platforms to advanced diagnostic issues related to emerging infections, increasing of fastidious bacteria, and generation of patient-tailored phylotypes. This article is part of a Special Issue entitled: Trends in Microbial Proteomics.

HIPK2 is involved in cell proliferation and its suppression promotes growth arrest independently of DNA damage.

INTRODUCTION/OBJECTIVES: The serine/threonine kinase homeodomain-interacting protein kinase 2 (HIPK2) is a co-regulator of an increasing number of transcription factors and cofactors involved in DNA damage response and development. We and others have cloned HIPK2 as an interactor of the p53 oncosuppressor, and have studied the role of this interaction in cell response to stress. Nevertheless, our original cloning of HIPK2 as a p53-binding protein, was aimed at discovering partners of p53 involved in cell differentiation and development, still controversial p53 functions. To this aim, we used p53 as bait in yeast two-hybrid screening of a cDNA library from mouse embryo (day 11 postcoitus) when p53 is highly expressed. METHODS AND RESULTS: In this study, we directly explored whether HIPK2 and p53 cooperate in cell differentiation. By measuring HIPK2 expression and activity in skeletal muscle and haemopoietic differentiation, we observed inverse behaviour of HIPK2 and p53--excluding cooperation activity of these two factors in this event. However, by HIPK2 depletion experiments, we showed that drastic HIPK2 suppression promotes cell-cycle arrest by induction of the cyclin-dependent kinase inhibitor p21(Waf-1/Cip-1). HIPK2 activity is independent of DNA damage and takes place in cell-cycle-arresting conditions, such as terminal differentiation, growth factor deprivation, and G(0) resting. CONCLUSIONS: HIPK2 was found to be involved in cell-cycle regulation dependent on p21(Waf-1/Cip-1) and independent of DNA damage.

[Correlations between blood pressure values, familial hypertension and anthropometric parameters in a sample of 3-year-old children]. / Correlazione tra valori di pressione arteriosa, familiarità ipertensiva e parametri antropometrici in un campione di bambini di tre anni.

Nowadays evaluation of blood pressure in children is almost routine. In fact hypertension in adults may be preceded by high blood pressure values in childhood. In this study the authors examined systolic blood pressure (SBP) and diastolic blood pressure (DBP), height, weight, ponderosity index and family history of hypertension, in 261 3-year-old children, 139 boys and 122 girls. Average values of SBP were slightly but not significantly higher in males. Coefficients of linear regression and correlation for any pair of the different parameters (SBP-DBP and weight, SBP-DBP and height, SBP-DPB and ponderosity index) were all significantly positive for males, but not for females. The most significant value (r = 0.43) was in the correlation DBP-weight. In studying the family history of hypertension all children were divided into three groups: negative (F.I.-), positive with brothers and/or parents affected (F.I. I+) and positive with other relatives affected (F.I. II+). Average SBP and DPB in the second group were higher than in the third, and much higher than in the first group. These results suggest the importance of prevention in early childhood with alimentary education and serial blood pressure measurements. The individuation of borderline values is also very important.

[Congenital dysplasia of the hip. Preliminary results of a longitudinal study in the first 6 months of life]. / La displasia congenita dell'anca (DCA). Risultati preliminari di uno studio longitudinale nei primi 6 mesi di vita.

The authors report their experience of a serial follow-up for congenital dysplasia of the hip (CDH). 699 babies born during a three-months period were examined on their first day of life, on the forth and at the age of 1 and 6 months. 2 dislocated hips, 222 clicking hips were discovered in the neonatal period. At the first month 1 dislocated hip and only 6 clicking hips were detected. At the sixth month all babies were normal with the exception of two clicking hips. X-ray examination confirmed clinical dislocation diagnosis and showed pathological signs (subluxation and acetabular dysplasia) also in normal and clicking hips. According to their results the authors suggest that clinical examination during the first 6 months of life and X-ray can decrease the incidence of late diagnosis of CDH.