Diversity of cervical microbiota in asymptomatic chlamydia trachomatis genital infection: a pilot study

Chlamydia trachomatis genital infection continues to be an important public health problem worldwide due to its increasing incidence. C. trachomatis infection can lead to severe sequelae, such as pelvic inflammatory disease, obstructive infertility, and preterm birth. Recently, it has been suggested that the cervico-vaginal microbiota may be an important defense factor toward C. trachomatis infection as well as the development of chronic sequelae. Therefore, the investigation of microbial profiles associated to chlamydial infection is of the utmost importance. Here we present a pilot study aiming to characterize, through the metagenomic analysis of sequenced 16s rRNA gene amplicons, the cervical microbiota from reproductive age women positive to C. trachomatis infection. The main finding of our study showed a marked increase in bacterial diversity in asymptomatic C. trachomatis positive women as compared to healthy controls in terms of Shannon's diversity and Shannon's evenness (P = 0.031 and P = 0.026, respectively). More importantly, the cervical microbiota from C. trachomatis positive women and from healthy controls significantly separated into two clusters in the weighted UniFrac analysis (P = 0.0027), suggesting that differences between the two groups depended entirely on the relative abundance of bacterial taxa rather than on the types of bacterial taxa present. Furthermore, C. trachomatis positive women showed an overall decrease in Lactobacillus spp. and an increase in anaerobes. These findings are part of an ongoing larger epidemiological study that will evaluate the potential role of distinct bacterial communities of the cervical microbiota in C. trachomatis infection

Whole exome sequencing in an Italian family with isolated maxillary canine agenesis and canine eruption anomalies

Objective: The aim of this study was the clinical and molecular characterization of a family segregating a trait consisting of a phenotype specifically involving the maxillary canines, including agenesis, impaction and ectopic eruption, characterized by incomplete penetrance and variable expressivity. Design: Clinical standardized assessment of 14 family members and a whole-exome sequencing (WES) of three affected subjects were performed. WES data analyses (sequence alignment, variant calling, annotation and prioritization) were carried out using an in-house implemented pipeline. Variant filtering retained coding and splice-site high quality private and rare variants. Variant prioritization was performed taking into account both the disruptive impact and the biological relevance of individual variants and genes. Sanger sequencing was performed to validate the variants of interest and to carry out segregation analysis. Results: Prioritization of variants “by function” allowed the identification of multiple variants contributing to the trait, including two concomitant heterozygous variants in EDARADD (c.308C>T, p.Ser103Phe) and COL5A1 (c.1588G>A, p.Gly530Ser), specifically associated with a more severe phenotype (i.e. canine agenesis). Differently, heterozygous variants in genes encoding proteins with a role in the WNT pathway were shared by subjects showing a phenotype of impacted/ectopic erupted canines. Conclusions: This study characterized the genetic contribution underlying a complex trait consisting of isolated canine anomalies in a medium-sized family, highlighting the role of WNT and EDA cell signaling pathways in tooth development

Applied Tests to Select the Most Suitable Fungal Strain for the Recovery of Critical Raw Materials from Electronic Waste Powder

Electrical and electronic wastes (WEEEs) are a potential source of raw materials. The main challenge for scientists is to set up a reliable and eco-friendly process to recycle raw materials and precious elements from WEEEs. Today, we know that fungi could play an active role in green technologies aimed at recycling valuable elements. The bioaccumulation mechanism and bioleaching activity of filamentous fungal species have already been exploited fruitfully in extraction processes. However, not all fungal strains possess the same characteristics, and it is crucial to choose the right strains to use. In this work, we show a method to assess the precious elements’ recovery efficiency from WEEE using fungal strains. A CAS agar screening test for siderophore detection was carried out with three strains. The following plate accumulation test performed on a medium added with 120 ppm of electronic waste powder highlighted the differences in accumulation capability, growth rate, and biomass production. Among the elements in tested waste, yttrium, copper, and palladium show the highest bioconcentration factor. The results confirm the biotechnological potential of fungi to recover valuable elements at the bench scale, highlighting the importance of effective screening tests to assess the most efficient strain for each kind of waste

SARS-CoV-2 vertical transmission in a twin-pregnant woman. A case report

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS- CoV-2) has affected millions of people around the world in the last years. Among susceptible patients, pregnant women seem to be prone to have serious complications. The possibility of SARS-CoV-2 vertical transmission represents one of the most debated topics in the literature, providing inconclusive results. We present a case of a confirmed vertical transmission in a monochorial diamniotic twin pregnancy complicated by a selective intrauterine growth restriction (sIUGR) and gestational diabetes. The analysis of different biological specimens identifies the presence of SARS-CoV2 genome in the umbilical cord blood of both twins and the placental histologic examination confirmed indirect signs of viral infection, supporting the hypothesis that a transplacental infection can occur. Despite the devastating impact that SARS-CoV2 has worldwide, neonatal infections have been infrequently reported but they can occur under certain biologic conditions. A deep knowledge of the biological mechanisms underlying the risk of SARS-CoV-2 vertical transmission might be useful to understand the pathophysiological bases and the possible long-term implication of a mother-to-child vertical transmission

SARS-CoV-2 infection in pregnancy. Clues and proof of adverse outcomes

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) represents one of the most threatening viral infections in the last decade. Amongst susceptible individuals, infected pregnant women might be predisposed to severe complications. Despite the extensive interest in SARS-CoV-2 research, the clinical course of maternal infection, the vertical transmission and the neonatal outcomes have not been completely understood yet. The aim of our study was to investigate the association between SARS-CoV-2 infection, obstetric outcomes and vertical transmission. Methods: A prospective observational study was performed, enrolling unvaccinated pregnant patients positive for SARS-CoV-2 (cases) and matched with uninfected pregnant women (controls). Maternal and neonatal nasopharyngeal swabs, maternal and cord blood, amniotic fluid and placenta tissue samples were collected; blood samples were tested for anti-S and anti-N antibodies, and histologic examination of placental tissues was performed. Results: The cases showed a significant association with the development of some obstetric complications, such as intrauterine growth restriction and pregnancy-associated hypothyroidism and diabetes, as compared to controls; their newborns were more likely to have a low birth weight and an arterial umbilical pH less than 7. The viral genome was detected in maternal and cord blood and placental samples in six cases. Conclusions: Pregnant women positive for SARS-CoV-2 infection are more likely to develop severe obstetric outcomes; their newborns could have a low birth weight and arterial pH. Vertical transmission seems a rare event, and further investigation is strongly needed

SMARCE1-related meningiomas: A clear example of cancer predisposing syndrome

We report the case of a 16-year-old girl presenting with spinal clear-cell multiple meningiomas (CCMs). In view of this presentation, we sequenced a bioinformatic panel of genes associated with susceptibility to meningioma, identifying a germline heterozygous variant in SMARCE1. Somatic DNA investigations in the CCM demonstrated the deletion of the wild-type allele (loss of heterozygosity, LOH), supporting the causative role of this variant. Family segregation study detected the SMARCE1 variant in the asymptomatic father and in the asymptomatic sister who, nevertheless, presents 2 spinal lesions. Germline heterozygous loss-of-function (LoF) variants in SMARCE1, encoding a protein of the chromatin-remodeling complex SWI/SNF, have been described in few fa-milial cases of susceptibility to meningioma, in particular the CCM subtype. Our case confirms the role of NGS in investigating predisposing genes for meningiomas (multiple or recurrent), with specific regard to SMARCE1 in case of pediatric CCM. In addition to the age of onset, the presence of familial clustering or the coexistence of multiple synchronous meningiomas also supports the role of a genetic predisposition that deserves a molecular assessment. Additionally, given the incomplete penetrance, it is of great importance to follow a specific screening or follow-up program for symptomatic and asymptomatic carriers of pathogenic variants in SMARCE1

The Interaction between Reactive Peritoneal Mesothelial Cells and Tumor Cells via Extracellular Vesicles Facilitates Colorectal Cancer Dissemination

Simple SummaryEmerging 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-beta 1 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

Gastric stump cancer after distal gastrectomy for benign disease: clinicopathological features and surgical outcomes.

The purpose of the present study was to analyze clinicopathologic features and long-term prognosis of gastric stump cancer (GSC) arising in the remnant stomach 5 years or later after partial gastrectomy for benign disease. METHODS: We reviewed the results of 176 patients resected with curative intent for GSC at 8 Italian centers belonging to the Italian Research Group for Gastric Cancer (GIRCG). The median (range) follow-up time for surviving patients was 71.2 (6-207) months. RESULTS: One hundred forty-six patients were men, the mean age at the time of diagnosis was 69.2 years, and the great majority (167 cases) underwent Billroth II reconstruction. R0 resection was achieved in 158 (90 %) patients, and in 94 (53 %) lymph node dissection was 65D2. Postoperative mortality and complication rates were 6.2 and 43.2 %, respectively. T1 tumor was diagnosed in 45 (25 %) cases. Lymph node metastases were evident in 86 patients (49 %). Thirteen patients had involvement of the jejunal mesentery nodes (pJN+); five cases were T2-T3 and eight cases were T4. Overall 5-year survival rate was 53.1 %. Five-year survival rates were 68.1, 37.8, and 33.1 % for pT1, pT2-3, and pT4 tumors, respectively (P = 0.001). Five-year survival rate was 56.5 % for node-negative tumors (pN0), 32.3 % for tumors with nodal metastases without involvement of jejunal mesentery nodes (pN+), and 17.1 % for tumors with involvement of jejunal mesentery nodes (pJN+) (P = 0.002). CONCLUSIONS: Our study suggests that an aggressive surgical approach can achieve a satisfactory outcome in GSC

CHK1 inhibitor sensitizes resistant colorectal cancer stem cells to nortopsentin

Limited therapeutic options are available for advanced colorectal cancer (CRC). Herein, we report that exposure to a neo-synthetic bis(indolyl)thiazole alkaloid analog, nortopsentin 234 (NORA234), leads to an initial reduction of proliferative and clonogenic potential of CRC sphere cells (CR-CSphCs), followed by an adaptive response selecting the CR-CSphC-resistant compartment. Cells spared by the treatment with NORA234 express high levels of CD44v6, associated with a constitutive activation of Wnt pathway. In CR-CSphC-based organoids, NORA234 causes a genotoxic stress paralleled by G2-M cell cycle arrest and activation of CHK1, driving the DNA damage repair of CR-CSphCs, regardless of the mutational background, microsatellite stability, and consensus molecular subtype. Synergistic combination of NORA234 and CHK1 (rabusertib) targeting is synthetic lethal inducing death of both CD44v6-negative and CD44v6-positive CRC stem cell fractions, aside from Wnt pathway activity. These data could provide a rational basis to develop an effective strategy for the treatment of patients with CRC

Physical activity in liver transplant recipients: a large multicenter study

Aim Healthy lifestyle and appropriate diet are of critical importance after liver transplant (LT). We provided an analysis of the main patterns of physical activity and found factors associated with physical activity itself.Methods Clinically stable LT recipients were enrolled between June and September 2021. Patients completed a composite questionnaire about physical activity, adherence to Mediterranean Diet (MD), quality of life (QoL), and employment. Correlations were analysed using the Pearson coefficients while different subgroups were compared by t-test for independent samples or ANOVAs. Multivariable logistic regression analysis was conducted to find predictors of inactivity.Results We enrolled 511 subjects (71% males, mean age 63 +/- 10.8 years). One hundred and ninety-three patients reported high level of physical activity, 197 a minimal activity and 121 declared insufficient activity. Among these latter, 29 subjects were totally inactive. Considering the 482 LT recipients performing some kind of physical activity, almost all reported a low-quality, non-structured activity. At multivariate analysis, time from LT (odds ratio 0.94, 95% CI 0.89-0.99, p = 0.017), sedentary lifestyle (odds ratio 0.99, 95% CI 0.19-0.81, p = 0.012), low adherence to MD (odds ratio 1.22, 95% CI 1.01-1.48, p = 0.049), and low level of QoL (physical dimension) (odds ratio 1.13, 95% CI 1.08-1.17, p < 0.001), were independently associated with total inactivity.Conclusion A large portion of LT recipients report an insufficient level of physical activity or are wholly inactive. Inactivity increases with time from LT and was strongly associated with suboptimal diet and low QoL