Search

Gynecomastia is a benign glandular proliferation that can affect adolescents causing significant psychological discomfort. Generally, it is idiopathic but underlying endocrinological conditions must be excluded. Different surgical techniques are available, the surgical correction with subareolar incision achieves the goal of satisfactory aesthetic result for patients. We studied all patients treated for gynecomastia in two centers of pediatric surgery. After collection of a detailed family history, we evaluated the presence of early onset of puberty, congenital abnormalities of the external genitalia, use of drugs, eating habits and the presence of genetic disorders. Laboratory tests and ultrasound were made to exclude endocrinological disorders. The surgical treatment was performed by a subareolar incision with gland and adipose tissue excision. A Body - Q chest module to evaluate patient satisfaction has been proposed to everyone before and after surgery. 47 adolescents with median age of 15 years were surgically treated. Three presented endocrinological disorders. Grade of gynecomastia for surgery was: III in 40 patients and IIb in 7 patients. Postoperative complications occurred in 5 patients. The Body - Q chest module was completed by 42 patients and showed good results for all points analyzed, except for social feelings. Gynecomastia in adolescents can be surgically treated with subareolar incision, reporting good aesthetic results and low incidence of complications. Specific tests are useful to assess patient satisfaction.

Abstract Background Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor, that is refractory to standard treatment and to immunotherapy with immune-checkpoint inhibitors (ICI). Noteworthy, melanoma brain metastases (MM-BM), that share the same niche as GBM, frequently respond to current ICI therapies. Epigenetic modifications regulate GBM cellular proliferation, invasion, and prognosis and may negatively regulate the cross-talk between malignant cells and immune cells in the tumor milieu, likely contributing to limit the efficacy of ICI therapy of GBM. Thus, manipulating the tumor epigenome can be considered a therapeutic opportunity in GBM. Methods Microarray transcriptional and methylation profiles, followed by gene set enrichment and IPA analyses, were performed to study the differences in the constitutive expression profiles of GBM vs MM-BM cells, compared to the extracranial MM cells and to investigate the modulatory effects of the DNA hypomethylating agent (DHA) guadecitabine among the different tumor cells. The prognostic relevance of DHA-modulated genes was tested by Cox analysis in a TCGA GBM patients’ cohort. Results The most striking differences between GBM and MM-BM cells were found to be the enrichment of biological processes associated with tumor growth, invasion, and extravasation with the inhibition of MHC class II antigen processing/presentation in GBM cells. Treatment with guadecitabine reduced these biological differences, shaping GBM cells towards a more immunogenic phenotype. Indeed, in GBM cells, promoter hypomethylation by guadecitabine led to the up-regulation of genes mainly associated with activation, proliferation, and migration of T and B cells and with MHC class II antigen processing/presentation. Among DHA-modulated genes in GBM, 7.6% showed a significant prognostic relevance. Moreover, a large set of immune-related upstream-regulators (URs) were commonly modulated by DHA in GBM, MM-BM, and MM cells: DHA-activated URs enriched for biological processes mainly involved in the regulation of cytokines and chemokines production, inflammatory response, and in Type I/II/III IFN-mediated signaling; conversely, DHA-inhibited URs were involved in metabolic and proliferative pathways. Conclusions Epigenetic remodeling by guadecitabine represents a promising strategy to increase the efficacy of cancer immunotherapy of GBM, supporting the rationale to develop new epigenetic-based immunotherapeutic approaches for the treatment of this still highly deadly disease.

Mucosal enrichment of the Adherent-Invasive E. coli (AIEC) pathotype and the expansion of pathogenic IFNγ-producing Th17 (pTh17) cells have been linked to Crohn’s Disease (CD) pathogenesis. However, the molecular pathways underlying the AIEC-dependent pTh17 cell transdifferentiation in CD patients remain elusive. To this aim, we created and functionally screened a transposon AIEC mutant library of 10.058 mutants to identify the virulence determinants directly implicated in triggering IL-23 production and pTh17 cell generation. pTh17 cell transdifferentiation was assessed in functional assays by co-culturing AIEC-infected human dendritic cells (DCs) with autologous conventional Th17 (cTh17) cells isolated from blood of Healthy Donors (HD) or CD patients. AIEC triggered IL-23 hypersecretion and transdifferentiation of cTh17 into pTh17 cells selectively through the interaction with CD-derived DCs. Moreover, the chronic release of IL-23 by AIEC-colonized DCs required a continuous IL-23 neutralization to significantly reduce the AIEC-dependent pTh17 cell differentiation. The multi-step screenings of the AIEC mutant’s library revealed that deletion of ybaT or rfaP efficiently hinder the IL-23 hypersecretion and hampered the AIEC-dependent skewing of protective cTh17 into pathogenic IFNγ-producing pTh17 cells. Overall, our findings indicate that ybaT (inner membrane transport protein) and rfaP (LPS-core heptose kinase) represent novel and attractive candidate targets to prevent chronic intestinal inflammation in CD.

Static infusion of oak chips in wine is a common practice during wine ageing, aimed at improving sensory properties and stability of wines. The wine/chips contact required to reach the desired effect can last several weeks or months. A low-pressure continuous dynamic (LPCD) extractor in which a closed-circle, low-pressure continuous flow of wine passes through an extraction cell filled with chips, was evaluated as a tool to tune red wine properties in few hours. The aim of this work was to evaluate the effect of the use of a LPCD extractor the effect on color, volatile compounds and sensory properties of a Primitivo wine, as well as to assess the combined effect of LPCD extractor, passive microxygenation through polyethylenetereftalate (PET) containers and exogenous tannins.Their combined effect caused a significant increase of stabilized pigments was observed, without compromising the aroma profile.LPCD extraction, passive micro-oxygenation through plastic materials and enological tannins can be considered as a low-cost, and potentially low-impact, integrated technological platform suitable to tune wine sensory properties and stability, when either traditional approaches (such as barrel aging) or other assisted extraction technologies are not applicable or preferred, even in small wineries.

IntroductionSARS-CoV-2 pandemic still poses a significant burden on global health and economy, especially for symptoms persisting beyond the acute disease. COVID-19 manifests with various degrees of severity and the identification of early biomarkers capable of stratifying patient based on risk of progression could allow tailored treatments.MethodsWe longitudinally analyzed 67 patients, classified according to a WHO ordinal scale as having Mild, Moderate, or Severe COVID-19. Peripheral blood samples were prospectively collected at hospital admission and during a 6-month follow-up after discharge. Several subsets and markers of the innate and adaptive immunity were monitored as putative factors associated with COVID-19 symptoms.ResultsMore than 50 immunological parameters were associated with disease severity. A decision tree including the main clinical, laboratory, and biological variables at admission identified low NK-cell precursors and CD14+CD91+ monocytes, and high CD8+ Effector Memory T cell frequencies as the most robust immunological correlates of COVID-19 severity and reduced survival. Moreover, low regulatory B-cell frequency at one month was associated with the susceptibility to develop long COVID at six months, likely due to their immunomodulatory ability.DiscussionThese results highlight the profound perturbation of the immune response during COVID-19. The evaluation of specific innate and adaptive immune-cell subsets allows to distinguish between different acute and persistent COVID-19 symptoms.

Sulfur dioxide (SO2) is one of the most used additives in wine industry for its antioxidant and antimicrobial activity. However, due to health concerns, consumers’ demand of wines with either reduced or totally replaced SO2 has increased. This study aimed to assess the effect of partial and total replacement of SO2 with a vine-shoots extract rich in stilbenes in rosé (cv. Sangiovese) and red (cv. Negramaro) wines respectively. Color as well as phenolic, volatile, and sensory profiles of wines were evaluated at bottling and during storage.The results showed that the vine-shoots extract increased the levels of trans-resveratrol, catechin, and gallic acid in wines. Moreover, the positive correlation of procyanidin dimers in red wine suggested an increase of the polymerization reactions. The amount of added extract probably provided lower antimicrobial protection compared to SO2, as indicated by the higher levels of ethyl phenol. The decrease of individual anthocyanins and oxidation aldehydes observed in wines with SO2 replacement and the higher levels of caftaric acid in the rosé wine with the extract suggested a shift of the oxidative protection, with a lower protection towards anthocyanin degradation and higher protection towards carbonyl formation and oxidation of readily oxidizable phenolic acids.

The main advantage of the laparo-assisted transanal endorectal pull-through technique (LA - TERPT) for Hirschsprung Disease (HD) is the respect to the rectal-anal anatomy. Postoperative complications have been observed recently. The present study aims to determine how often these postoperative complications occur in these patients. From January 2009 to December 2018, a retrospective analysis was conducted on 36 children (25 males) with HD who underwent LA-TERPT. Data were collected on the age of diagnosis and surgery, sex, the presence of other pathologies, and cases of enterocolitis. In all cases, anorectal manometry (ARM) was performed to evaluate the anal tone. The median age at diagnosis was 2 months and the mean age at surgery was 5 months. Nine related pathologies were identified: five cases of Down syndrome, one case of hypertrophic stenosis of the pylorus, atresia of the esophagus, polydactyly, and anorectal malformation. A patient with total colonic aganglionosis was identified through laparoscopic serummuscular biopsies. Enterocolitis was diagnosed in 7 cases before and 6 after surgery. At follow-up, the complications recorded were: 5 cases of constipation (treated with fecal softeners), one case of anal stenosis (patient with anorectal malformation), 16 cases of soiling (treated with enemas) and 1 child with fecal incontinence (treated with a transanal irrigation system). The ARM was performed in all 36 cases and showed normal anal tone, except for one case with anal hypotonia. LA-TERPT is an important surgical technique for HD. According to the literature, soiling is the most main complication after HD surgery, probably due to “pseudo-incontinence” with normal anal sphincter tone.

This paper deals with the imaging problem from data collected by means of a microwave photonics-based distributed radar network. The radar network is leveraged on a centralized architecture, which is composed of one central unit (CU) and two transmitting and receiving dual-band remote radar peripherals (RPs), it is capable of collecting monostatic and multistatic phase-coherent data. The imaging is herein formulated as a linear inverse scattering problem and solved in a regularized way through the truncated singular value decomposition inversion scheme. Specifically, two different imaging schemes based on an incoherent fusion of the tomographic images or a fully coherent data processing are herein developed and compared. Experimental tests carried out in a port scenario for imaging both a stationary and a moving target are reported to validate the imaging approach.

MicroRNAs (miRNAs) are involved in post-transcriptional gene expression regulation and in mechanisms of cancer growth and metastases. In this light, miRNAs could be promising therapeutic targets and biomarkers in clinical practice. Therefore, we investigated if specific miRNAs and their target genes contribute to laryngeal squamous cell carcinoma (LSCC) development. We found a significant decrease of miR-449a in LSCC patients with nodal metastases (63.3%) compared with patients without nodal involvement (44%). The AmpliSeq Transcriptome of HNO-210 miR-449a-transfected cell lines allowed the identification of IL6-R as a potential target. Moreover, the downregulation of IL6-R and the phosphorylation reduction of the downstream signaling effectors, suggested the inhibition of the IL-6 trans-signaling pathway. These biochemical effects were paralleled by a significant inhibition of invasion and migration in vitro and in vivo, supporting an involvement of epithelial-mesenchymal transition. These findings indicate that miR-449a contributes to suppress the metastasization of LSCC by the IL-6 trans-signaling block and affects sensitivity to external stimuli that mimic pro-inflammatory conditions.

Ageing wine in barrels is an historical practice used to improve the aromatic complexity of wine, but due to the high cost and the long ageing period, alternative approaches have been developed, such as the use of wood chips and ultrasound treatment. The present paper reports the results of an investigation performed on wine (cv. Primitivo). Three treatments were investigated: a) control wine untreated; b) wine with toasted vine-shoot chips (10 g/L); c) wine with toasted vine-shoot chips (10 g/L) and treated by ultrasound. Wines were analysed after 7, 14, 21, and 28 days. The application of ultrasound combined with vine-shoot chips promoted tannin evolution, thereby accelerating the ageing process of wine. The chips addition decreased the total anthocyanins content and increased the stilbenes (trans-resveratrol and trans-piceid) and wood-related aromas (i.e., furfural, 5-methylfurfural) concentration. Finally, wines added with chips were richer in woody, vanilla, oak, and chocolate notes and more preferred by the tasters.

Abstract Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, including 111 from the NE, across 68 HGG patients. Whole exome and RNA sequencing uncover unique genomic alterations to unresectable invasive NE tumor, including subclonal events, which inform genomic models predictive of geographic evolution. Infiltrative NE tumor is alternatively enriched with tumor cells exhibiting neuronal or glycolytic/plurimetabolic cellular states, two principal transcriptomic pathway-based glioma subtypes, which respectively demonstrate abundant private mutations or enrichment in immune cell signatures. These NE phenotypes are non-invasively identified through normalized K2 imaging signatures, which discern cell size heterogeneity on dynamic susceptibility contrast (DSC)-MRI. NE tumor populations predicted to display increased cellular proliferation by mean diffusivity (MD) MRI metrics are uniquely associated with EGFR amplification and CDKN2A homozygous deletion. The biophysical mapping of infiltrative HGG potentially enables the clinical recognition of tumor subpopulations with aggressive molecular signatures driving tumor progression, thereby informing precision medicine targeting.

Abstract Association with hypomethylating agents is a promising strategy to improve the efficacy of immune checkpoint inhibitors-based therapy. The NIBIT-M4 was a phase Ib, dose-escalation trial in patients with advanced melanoma of the hypomethylating agent guadecitabine combined with the anti-CTLA-4 antibody ipilimumab that followed a traditional 3 + 3 design (NCT02608437). Patients received guadecitabine 30, 45 or 60 mg/m2/day subcutaneously on days 1 to 5 every 3 weeks starting on week 0 for a total of four cycles, and ipilimumab 3 mg/kg intravenously starting on day 1 of week 1 every 3 weeks for a total of four cycles. Primary outcomes of safety, tolerability, and maximum tolerated dose of treatment were previously reported. Here we report the 5-year clinical outcome for the secondary endpoints of overall survival, progression free survival, and duration of response, and an exploratory integrated multi-omics analysis on pre- and on-treatment tumor biopsies. With a minimum follow-up of 45 months, the 5-year overall survival rate was 28.9% and the median duration of response was 20.6 months. Re-expression of immuno-modulatory endogenous retroviruses and of other repetitive elements, and a mechanistic signature of guadecitabine are associated with response. Integration of a genetic immunoediting index with an adaptive immunity signature stratifies patients/lesions into four distinct subsets and discriminates 5-year overall survival and progression free survival. These results suggest that coupling genetic immunoediting with activation of adaptive immunity is a relevant requisite for achieving long term clinical benefit by epigenetic immunomodulation in advanced melanoma patients.

Ovarian torsion (OT) is a condition that can affect both humans and animals, although it is less common in the latter, with very few cases documented in the literature. To our knowledge, no previous reports have documented the occurrence of this condition in rabbits. In this study, we present the first documented case of spontaneous OT in a 2-year-old female intact rabbit. The patient was brought to the clinic for a routine check-up, during which a firm, large abdominal mass was palpated. Subsequent ultrasound examination of the abdomen revealed the presence of a large, hypoechoic, non-vascularized mass occupying the majority of the caudal abdomen. A computed tomography (CT) scan further confirmed the presence of a heterogeneous mass exhibiting the Whirlpool sign, which is characteristic of organ torsion. Upon laparotomy, an enlargement of the right ovary was observed, characterized by twisting of the ovarian pedicle, consistent with the mass detected via ultrasound and CT scan. Ovariohysterovaginectomy was performed, and the mass was subsequently analyzed. Microscopic analysis of the mass revealed predominantly necrotic tissue, with only a few ovarian epithelial cells present. The underlying cause of the OT described in this study remains unclear. However, it is plausible that a previous neoplastic condition or ovarian necrosis led to an increase in the size and weight of the mass, ultimately resulting in the twisting of the supporting structures.

Hypereosinophilic syndrome (HES) encompasses a heterogeneous and complex group of different subtypes within the wider group of hypereosinophilic disorders. Despite increasing research interest, several unmet needs in terms of disease identification, pathobiology, phenotyping, and personalized treatment remain to be addressed. Also, the prospective burden of non-malignant HES and, more in general, HE disorders is currently unknown. On a practical note, shortening the diagnostic delay and the time to an appropriate treatment approach probably represents the most urgent issue, even in light of the great impact of HES on the quality of life of affected patients. The present document represents the first action that the Italian Society of Allergy, Asthma, and Clinical Immunology (SIAAIC) has finalized within a wider project aiming to establish a collaborative national network on HES (InHES—Italian Network on HES) for patients and physicians. The first step of the project could not but focus on defining a common language as well as sharing with all of the medical community an update on the most recent advances in the field. In fact, the existing literature has been carefully reviewed in order to critically integrate the different views on the topic and derive practical recommendations on disease identification and treatment approaches.