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A structural weakness of the mucus barrier (MB) is thought to be a cause of ulcerative colitis (UC). This study aims to investigate the mucin (MUC) composition of MB in normal mucosa and UC. Ileocolonic biopsies were taken at disease onset and after treatment in 40 patients, including 20 with relapsing and 20 with remitting UC. Ileocolonic biopsies from 10 non-IBD patients were included as controls. Gut-specific MUC1, MUC2, MUC4, MUC5B, MUC12, MUC13, MUC15, and MUC17 were evaluated immunohistochemically. The promoters of mucin genes were also examined. Normal mucosa showed MUC2, MUC5B, and MUC13 in terminal ileum and colon, MUC17 in ileum, and MUC1, MUC4, MUC12, and MUC15 in colon. Membranous, cytoplasmic and vacuolar expressions were highlighted. Overall, the mucin expression was abnormal in UC. Derangements in MUC1, MUC4, and MUC5B were detected both at onset and after treatment. MUC2 and MUC13 were unaffected. Sequence analysis revealed glucocorticoid-responsive elements in the MUC1 promoter, retinoic-acid-responsive elements in the MUC4 promoter, and butyrate-responsive elements in the MUC5B promoter. In conclusion, MUCs exhibited distinct expression patterns in the gut. Their expression was disrupted in UC, regardless of the treatment protocols. Abnormal MUC1, MUC4, and MUC5B expression marked the barrier dysfunction in UC. [ABSTRACT FROM AUTHOR]

Polychlorinated biphenyls (PCBs) are persistent organic pollutants and endocrine disruptors that have been implicated in potential damage to human semen. However, the studies conducted so far provide contrasting results. Our study aimed to investigate the associations between PCB serum and semen levels and semen quality in high school and university students living in a highly PCB-polluted area of Italy. Subjects with a normal body mass index who did not make daily use of tobacco, alcohol, drugs, or medication were selected. All participants provided a fasting blood and a semen sample. Gas chromatography-mass spectrometry was used to determine the concentrations of 26 PCB congeners. The concentrations of PCB functional groups and total PCBs were also computed. A total of 143 subjects (median age 20, range 18–22 years) were enrolled. The median total PCB concentrations were 3.85 ng/mL (range 3.43–4.56 ng/mL) and 0.29 ng/mL (range 0.26–0.32 ng/mL) in serum and semen, respectively. The analysis of the associations between sperm PCB concentration and semen parameters showed (a) negative associations between some PCB congeners, functional groups and total PCBs and sperm total motility; (b) negative associations of total PCBs with sperm normal morphology; and (c) no association of PCBs with sperm concentration. Subjects at the highest quartile of semen total PCB concentration had 19% and 23% mean reductions in total motility and normal morphology, respectively, compared to those at the lowest quartile. The analysis of the associations of serum PCB levels with sperm parameters yielded null or mixed (some positive, other negative) results. In conclusion, the present study provides evidence of a negative effect of some PCB congeners and total PCBs in semen on sperm motility and normal morphology. However, the associations between the concentration of serum and semen PCB congeners and functional groups and sperm quality parameters were inconsistent. [ABSTRACT FROM AUTHOR]

Simple Summary: Microinvasive breast carcinoma is an infiltrating carcinoma that measures ≤1 mm. The prognostic factors associated with this disease have not been extensively investigated. In this study, we aimed to perform a systematic review and meta-analysis to examine the prognostic factors of microinvasive breast carcinoma. From 618 screened records, 5 were selected. The meta-analyses found a significant association between lymph node status and prognosis. No significant prognostic impacts were found for the following factors: estrogen receptor, progesterone receptor, HER2 status, multifocality or grade of microinvasion, or patient's age. Therefore, the data obtained demonstrate that lymph node status is a main prognostic factor of microinvasive breast carcinoma. (1) Background: The prognostic factors of microinvasive (≤1 mm) breast carcinoma are not completely clear. The aim of this study was to perform a systematic review and meta-analysis to clarify these factors. (2) Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was followed. Two databases were interrogated, PubMed and Embase, and papers in English were included to address this question. The selected studies were those that reported on female patients affected by microinvasive carcinoma, and on prognostic factors with a hazard ratio (HR) for disease-free survival (DFS) and overall survival (OS). (3) Results: In total, 618 records were identified. After removing duplicates (166), identification, and screening (336 by title and abstract alone, 116 by full text and eventual supplementary material), 5 papers were selected. Seven different meta-analyses were conducted in this study, all referring to DFS, analyzing the following prognostic factors: estrogen receptor, progesterone receptor, HER2 status, multifocality and grade of microinvasion, patient's age, and lymph node status. Only lymph node status was associated with prognosis and DFS (total number of cases: 1528; Z = 1.94; p = 0.05). The other factors examined did not significantly affect prognosis (p > 0.05). (4) Conclusions: Positive lymph node status significantly worsens prognosis in patients with microinvasive breast carcinoma. [ABSTRACT FROM AUTHOR]

In this paper, a new protocol is described, based on solid phase microextraction (SPME) coupled with gas chromatography–mass spectrometry (GC-MS), to monitor ex vivo changes in endogenous volatile organic compounds (VOCs) released by surgically resected colonic tissues (normal colonic mucosa and adenomatous polyps) from seven patients undergoing operative colonoscopy to identify their molecular pattern. The exhalated volatile organic molecules from these patients were sampled by the ReCIVA® breath sampler, shortly before surgery, and analyzed by GC-MS. Comparing VOC patterns identified in the tissues and in the breath of the same patients, a possible correlation can be found between the levels of methylbenzene and benzaldehyde exhaled and the presence of colonic adenomatous polypoid lesions. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) may result in end-stage renal disorder and an increased mortality rate. Presently, kidney transplantation represents the only definitive treatment to restore normal life expectancy. Nevertheless, there is an elevated risk of organ rejection in the short–medium term after surgery. This preclinic study proposes the optimization of an innovative, fast, non-invasive, and cheap thermal desorption-gas chromatograph–mass spectrometry (TD-GC–MS) protocol, which provides simple monitoring of the respiratory profile of CKD-affected patients, before and during the first year after surgery, and aims to preemptively predict the rejection of the transplanted kidney. Twenty volatile organic compounds (VOCs), known as targets and, which are representative of the major classes of molecules discriminating between CKD-affected patients and healthy individuals, were selected from the literature, and employed to optimize the methodology. Calibration curves, linearity concentration ranges, the limit of detection (LOD), and the limit of quantification (LOQ) were estimated for the chosen molecules as well as the intraday and interday reproducibility of the method. The applicability of the TD-GC–MS developed approach was tested by analyzing the breath of healthy and pathological subjects using the ReCIVA® device. Sixty-seven molecules were identified, and between these, thirteen of the twenty selected compounds were quantified and were identified to have high prognostic values. [ABSTRACT FROM AUTHOR]

Neoplasms with plasma cell differentiation may occasionally involve the skin. Cutaneous lesions may represent the first sign of an underlying systemic plasma cell malignancy, such as multiple myeloma, or the skin itself may be the primary site of occurrence of a hematological tumor with plasma cell differentiation. Starting from examples encountered in our daily practice, we discussed the diagnostic approach pathologists and clinicians should use when faced with cutaneous lesions with plasma cell differentiation. Cases of primary cutaneous marginal zone lymphoma, localized primary amyloidosis/amyloidoma, and cutaneous manifestations (secondary either to multiple myeloma or to plasmablastic lymphoma) are discussed, focusing on the importance of the adequate patient's work-up and precise clinicopathological correlation to get to the correct diagnosis and appropriate treatment. The pertinent literature has been reviewed, and the clinical presentation, pathological findings, main differential diagnoses, treatment, and outcome of neoplasms with plasma cell differentiation involving the skin are discussed. [ABSTRACT FROM AUTHOR]

Compartmental models have long been used in epidemiological studies for predicting disease spread. However, a major issue when using compartmental mathematical models concerns the time-invariant formulation of hyper-parameters that prevent the model from following the evolution over time of the epidemiological phenomenon under investigation. In order to cope with this problem, the present work suggests an alternative hybrid approach based on Machine Learning that avoids recalculation of hyper-parameters and only uses an initial set. This study shows that the proposed hybrid approach makes it possible to correct the expected loss of accuracy observed in the compartmental model when the considered time horizon increases. As a case study, a basic compartmental model has been designed and tested to forecast COVID-19 hospitalizations during the first and the second pandemic waves in Lombardy, Italy. The model is based on an extended formulation of the contact function that allows modelling of the trend of personal contacts throughout the reference period. Moreover, the scenario analysis proposed in this work can help policy-makers select the most appropriate containment measures to reduce hospitalizations and relieve pressure on the health system, but also to limit any negative impact on the economic and social systems. [ABSTRACT FROM AUTHOR]

Simple Summary: Emerging evidence has suggested that cancer-derived extracellular vesicles (EVs) have a crucial role in mediating directional metastasis to the peritoneal surface in colorectal cancer (CRC). We investigated the EV-mediated crosstalk between tumor and mesothelial cells which may drive remodeling of the premetastatic niche to allow tumor spread to the peritoneal surface. Our findings demonstrated that cancer-derived EVs triggered apoptosis and reduced mesothelial cell invasiveness and mesothelial-to-mesenchymal transition. On the other hand, mesothelial cells actively supported tumor invasion by releasing EVs, which induced upregulation of the major pro-invasive system in tumor cells. For the first time, we provide evidence of EV-driven mechanisms of CRC progression in patient-derived models, highlighting the crucial role of EVs in the reprogramming of mesothelial and tumor cells to establish the metastatic process. Advanced colorectal cancer (CRC) is highly metastatic and often results in peritoneal dissemination. The extracellular vesicles (EVs) released by cancer cells in the microenvironment are important mediators of tumor metastasis. We investigated the contribution of EV-mediated interaction between peritoneal mesothelial cells (MCs) and CRC cells in generating a pro-metastatic environment in the peritoneal cavity. Peritoneal MCs isolated from peritoneal lavage fluids displayed high CD44 expression, substantial mesothelial-to-mesenchymal transition (MMT) and released EVs that both directed tumor invasion and caused reprogramming of secretory profiles by increasing TGF-β1 and uPA/uPAR expression and MMP-2/9 activation in tumor cells. Notably, the EVs released by tumor cells induced apoptosis by activating caspase-3, peritoneal MC senescence, and MMT, thereby augmenting the tumor-promoting potential of these cells in the peritoneal cavity. By using pantoprazole, we reduced the biogenesis of EVs and their pro-tumor functions. In conclusion, our findings provided evidence of underlying mechanisms of CRC dissemination driven by the interaction of peritoneal MCs and tumor cells via the EVs released in the peritoneal cavity, which may have important implications for the clinical management of patients. [ABSTRACT FROM AUTHOR]

Background: The frequency of delayed bleeding after colorectal polypectomy has been reported as 0.6–2.8%. With the increasing performance of polypectomy under continuous use of antithrombotic agents, care is required regarding delayed post-polypectomy bleeding (DPPB). Better instruction to educate endoscopists is therefore needed. We aimed to evaluate the effect of instruction and factors associated with delayed bleeding after endoscopic colorectal polyp resection. Methods: This single-center, retrospective study was performed to assess instruction in checking complete hemostasis and risk factors for onset of DPPB. The incidence of delayed bleeding, comorbidities, and medications were evaluated from medical records. Characteristics of historical control patients and patients after instruction were compared. Results: A total of 3318 polyps in 1002 patients were evaluated. The control group comprised 1479 polyps in 458 patients and the after-instruction group comprised 1839 polyps in 544 patients. DPPB occurred in 1.1% of polyps in control, and 0.4% in after-instruction. Instruction significantly decreased delayed bleeding, particularly in cases with antithrombotic agents. Hot polypectomy, clip placement, and use of antithrombotic agents were significant independent risk factors for DPPB even after instruction. Conclusion: The rate of delayed bleeding significantly decreased after instruction to check for complete hemostasis. Even after instruction, delayed bleeding can still occur in cases with antithrombotic agents or hot polypectomy. [ABSTRACT FROM AUTHOR]

Gastric cancer is diagnosed in nearly one million new patients each year and it remains the second leading cause of cancer-related deaths worldwide. Although gastric cancer represents a heterogeneous group of diseases, chronic inflammation has been shown to play a role in tumorigenesis. Cancer development is a multistep process characterized by genetic and epigenetic alterations during tumour initiation and progression. The stromal microenvironment is important in maintaining normal tissue homeostasis or promoting tumour development. A plethora of immune cells (i.e., lymphocytes, macrophages, mast cells, monocytes, myeloid-derived suppressor cells, Treg cells, dendritic cells, neutrophils, eosinophils, natural killer (NK) and natural killer T (NKT) cells) are components of gastric cancer microenvironment. Mast cell density is increased in gastric cancer and there is a correlation with angiogenesis, the number of metastatic lymph nodes and the survival of these patients. Mast cells exert a protumorigenic role in gastric cancer through the release of angiogenic (VEGF-A, CXCL8, MMP-9) and lymphangiogenic factors (VEGF-C and VEGF-F). Gastric mast cells express the programmed death ligands (PD-L1 and PD-L2) which are relevant as immune checkpoints in cancer. Several clinical undergoing trials targeting immune checkpoints could be an innovative therapeutic strategy in gastric cancer. Elucidation of the role of subsets of mast cells in different human gastric cancers will demand studies of increasing complexity beyond those assessing merely mast cell density and microlocalization. [ABSTRACT FROM AUTHOR]