Sedimentation of Nanoparticles in in vitro Toxicity Assays

Attached extended abstract published in the conference proceedingsJRC.DG.I.5-Nanobioscience

Baseline reef health surveys at Bangka Island (North Sulawesi, Indonesia) reveal new threats

Worldwide coral reef decline appears to be accompanied by an increase in the spread of hard coral diseases. However, whether this is the result of increased direct and indirect human disturbances and/or an increase in natural stresses remains poorly understood. The provision of baseline surveys for monitoring coral health status lays the foundations to assess the effects of any such anthropogenic and/or natural effects on reefs. Therefore, the objectives of this present study were to provide a coral health baseline in a poorly studied area, and to investigate possible correlations between coral health and the level of anthropogenic and natural disturbances. During the survey period, we recorded 20 different types of coral diseases and other compromised health statuses. The most abundant were cases of coral bleaching, followed by skeletal deformations caused by pyrgomatid barnacles, damage caused by fish bites, general pigmentation response and galls caused by cryptochirid crabs. Instances of colonies affected by skeletal eroding bands, and sedimentation damage increased in correlation to the level of bio-chemical disturbance and/or proximity to villages. Moreover, galls caused by cryptochirid crabs appeared more abundant at sites affected by blast fishing and close to a newly opened metal mine. Interestingly, in the investigated area the percentage of corals showing signs of ‘common’ diseases such as black band disease, brown band disease, white syndrome and skeletal eroding band disease were relatively low. Nevertheless, the relatively high occurrence of less common signs of compromised coral-related reef health, including the aggressive overgrowth by sponges, deserves further investigation. Although diseases appear relatively low at the current time, this area may be at the tipping point and an increase in activities such as mining may irredeemably compromise reef health.This research was partially funded by Coral Eye, which hosted FF and covered all field expenses. The non-profit organization Reef Check Italia Onlus sustained the cost for open source publication. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Congenital Glioblastoma multiforme and eruptive disseminated Spitz nevi

Background: Glioblastoma multiforme (GBM) is the deadliest malignant primary brain tumor in adults. GBM develops primarily in the cerebral hemispheres but can develop in other parts of the central nervous system. Its congenital variant is a very rare disease with few cases described in literature. Case presentation: We describe the case of a patient with congenital GBM who developed eruptive disseminated Spitz nevi (EDSN) after chemotherapy. Few cases of EDSN have been described in literature and this rare clinical variant, which occurs predominantly in adults, is characterized by multiple Spitz nevi in the trunk, buttocks, elbows and knees. There is no satisfactory treatment for EDSN and the best therapeutic choice is considered the clinical observation of melanocytic lesions. Conclusion: We recommend a close follow-up of these patients with clinical observation, dermoscopy and reflectance confocal microscopy (RCM). However, we suggest a surgical excision of the lesions suspected of being malignant

Pharmacological counseling in hepatotoxicity induced by macitentan and selexipag: a case report

Background: Pulmonary arterial hypertension is a progressive, debilitating condition characterized by increased resistance in the pulmonary arterial circulation. Current treatments for pulmonary arterial hypertension include endothelin receptor antagonists such as bosentan, sitaxentan, ambrisentan, macitentan, and oral prostacyclin receptor agonists such as selexipag. Endothelin receptor antagonists have been associated with liver injury, while hepatotoxicity was not reported for selexipag. Although genetic variability has been indisputably associated with variability in drug response, no study has been designed until now to assess its effects on the pharmacokinetics of endothelin receptor antagonists or selexipag. Case presentation: We report the case of a 58-year-old female Caucasian patient with a dramatic increase in plasma levels of transaminases after treatment with macitentan and selexipag, drugs whose risk of causing liver injury has so far been considered limited. After therapy discontinuation, plasma levels of transaminases returned to baseline, thus suggesting a role of these drugs in the observed hepatotoxicity. After pharmacological counseling, we decided to introduce ambrisentan for the patient's treatment. After 7 months of treatment, no liver injury has been reported. To evaluate the role of genetic factors in the observed hepatotoxicity, we genotyped the patient for single-nucleotide polymorphisms previously associated with macitentan, ambrisentan, or selexipag metabolism. We found a genetic profile associated with a poor metabolizer (PM) phenotype for CYP2C8 and CYP2C9, key enzymes for elimination of both macitentan and selexipag. The reported results suggest that an allelic profile associated with low activity for CYP2C8 and CYP2C9 enzyme could be a potential risk factor for macitentan and selexipag-induced liver injury and could provide a possible marker for early identification of subjects at higher risk of developing hepatotoxicity. Conclusions: A multidisciplinary approach based on clinical evaluation, as well as pharmacological counseling and evaluation of the patient's genetic profile, might be useful for identification of patients with a high chance of drug-induced liver injury, avoiding unnecessary risks in therapy selection and prescription

Chemical and biological indicators of water quality in three agricultural watersheds of the Po valley, Italy

open9noAgriculture has both direct and indirect effects on quality of surface water and is one of the key activities causing water quality degradation. Its environmental impact can be evaluated by the determination of indicators of the quality of water bodies that collect drainage and runoff waters from agricultural watersheds. For this research, the water quality draining from three watersheds, totally or partially cultivated, all within the Po river valley (Italy), was determined, using chemical indicators (N-NO3 and N-NH4 concentration, N balance), trophic status (chlorophyll-a concentration) and benthic population indexes. Together, they should provide an overview of the water status, which is supposed to be strictly related to the land use and the management. Results show that the chemical parameters are well related to land use and farming management: intensive agricultural activity leads to high N-NO3 concentration in water and N surplus and vice versa. The chlorophyll-a concentration follows the same trend, being linked to nitrogen loads and land use. Not always there is accordance between chemical and biological indicators: no direct correspondence is evident between the N-NO3 concentration in waters and benthic community. Its presence and abundance seems to be mostly correlated with the geomorphology, hydrology, riparian strips, etc. of the habitat than to the land use. Only the integration of chemical and biological parameters allows a correct understanding of the state of health of water body and benthic communities.openPIERI L.; VENTURA F.; VENTURA M.; TAGLIAVINI M.; PONTI M.; PISTOCCHI R.; ALBERTAZZI S.; VIGNUDELLI M.; ROSSI PISA P.PIERI L.; VENTURA F.; VENTURA M.; TAGLIAVINI M.; PONTI M.; PISTOCCHI R.; ALBERTAZZI S.; VIGNUDELLI M.; ROSSI PISA P

Chapter Il Piccolo Masaccio e le Terre Nuove. Creativity and Computer Graphics for Museum Edutainment

Since its opening, the Museum of the New Towns, housed in the Palazzo di Arnolfo in San Giovanni Valdarno, has dedicated a particular attention to the relationship with its audiences. In this context, the video “Il piccolo Masaccio e le Terre Nuove” has the purpose of bringing children and young people, in particular, closer to the museum main themes. The video presents a series of very different techniques, such as live shots, taken also by drone, Computer Graphics, 2D drawings executed with a tablet, drawings sketched with traditional techniques, such as India ink and watercolours, and digital videos taken from Google Earth

BRAFp.V600E, p.V600K, and p.V600R Mutations in Malignant Melanoma: Do They Also Differ in Immunohistochemical Assessment and Clinical Features?

Although the detection of BRAF p.V600E mutation by immunohistochemistry was clearly described in melanoma, discordant evidences were reported for the detection of p.V600K and p.V600R mutations. The aim of the study was to evaluate the efficacy of BRAFp.V600E, p.V600K, and p.V600R detection by immunohistochemistry in melanoma

Sphenoid asymmetry associated to other skeletal anomalies in a clear cut case of PTCH1 mutated Gorlin-Goltz syndrome: a novel finding?

Gorlin-Goltz syndrome is an autosomal dominantly inherited disorder linked to PTCH1 mutation, recognized by a collection of clinical and radiologic signs (macrocephaly, frontal bossing, multiple intracranial calcifications including falx cerebri and atlanto-occipital ligament). We describe here a the case of a family with clear cut criteria for Gorlin-Goltz syndrome presenting the association of cranio-facial and skeletal anomalies together with a peculiar sphenoid variant. Two patients, father and son, were examined because of multiple basal cell carcinomas and keratocystic odontogenic tumours. Other suggestive findings were multiple positive family history, typical skeletal anomalies and a novel PTCH1 germline mutation (c.1041delAA). Craniofacial and other skeletal anomalies displayed at 3D and helical CT scan were: macrocephaly, skull base asymmetry (positional plagiocephaly), mandibular prognathism, mandibular condylar deformation with hyperplasia of the coronoid process, bifidity of multiple ribs and giant multilocular odontogenic jaw cysts. Extensive multilamellar calcifications were found in falx cerebri, tentorium, falx cerebelli and in the apical segment of the atlanto-occipital ligament. Thoracic anomalies included bifid left 3rd, 4th, 5th and 6th rib, dismorphic body of the 3rd thoracic vertebra, dorsolumbar scoliosis, sacrum acutum. Interestingly, 3D-CT scan showed asymmetry of both sphenoid wings with thickening of the left wing sphenoid wing together with irregularity of the architecture of trabecular bone with alternating osteolytic and sclerotic areas. Abnormalities of the sphenoid bone are not very common, and consist of differently aggressive entities: some of them are typical of the pediatric age in few hereditary and congenital disorders. The application of new criteria (i.e. peculiar calcifications of ligaments and sphenoid asymmetry) to a wider case series can lead to the early diagnosis of Gorlin syndrome, especially in pediatric patients, when the full phenotype is not yet expressed. The inclusion of bifid ribs as a novel major criteria and the recognition of peculiar cranial anomalies such as sphenoid asymmetry, well detected at volume CT reconstruction, might be useful for the recognition and characterization of misdiagnosed cases

Epstein-Barr Virus in Cutaneous T-Cell Lymphomas: Evaluation of the Viral Presence and Significance in Skin and Peripheral Blood

The importance of viral agents in the development of cutaneous T-cell lymphomas (CTCL) is still debated. For this purpose, we retrospectively evaluated the Epstein-Barr virus (EBV) presence in Sézary syndrome (SS), mycosis fungoides (MF), inflammatory dermatoses (ID), and healthy donors (HD) using different approaches: EBV-DNA was quantified in skin biopsies and peripheral blood using real-time PCR, EBV-encoded small RNA (EBER) transcripts were detected by in situ hybridization (ISH), and latent membrane protein1-2 antigens were detected by immunohistochemistry. Skin biopsies were EBV-DNA-positive in 8/30 (27%) SS, 7/71 (10%) MF, and 2/18 (11%) ID patients and in none of the 25 normal skin samples. Positive mRNA (EBER) signals, always confined to cerebriform T lymphocytes, were found in 5/30 SS patients (17%), whereas signals in all MF and ID patients were negative. The presence of EBV-DNA in skin and blood samples was associated with a significantly lower survival in MF/SS patients. In evaluating EBV serological status, most (>70%) SS, MF, and ID patients showed a serological reactivation demonstrated by the presence of anti-EA IgG. In conclusion, although the finding of EBV-DNA in CTCL does not prove its etiopathogenetic role and may be related instead to immunosuppression, our study demonstrates that it has prognostic relevance

Possible implications for SARS-CoV-2 impact on brain development

Funding Information: The authors would like to thank Dr. Marc Peschanski (I-Stem, Évry, France) for providing IMR90-hiPSCs, and Dr. Anna Navarro Cuenca for providing the license for the use of BioRender.com. Publisher Copyright: © 2022The possible neurodevelopmental consequences of SARS-CoV-2 infection are presently unknown. In utero exposure to SARS-CoV-2 has been hypothesized to affect the developing brain, possibly disrupting neurodevelopment of children. Spike protein interactors, such as ACE2, have been found expressed in the fetal brain, and could play a role in potential SARS-CoV-2 fetal brain pathogenesis. Apart from the possible direct involvement of SARS-CoV-2 or its specific viral components in the occurrence of neurological and neurodevelopmental manifestations, we recently reported the presence of toxin-like peptides in plasma, urine and fecal samples specifically from COVID-19 patients. In this study, we investigated the possible neurotoxic effects elicited upon 72-hour exposure to human relevant levels of recombinant spike protein, toxin-like peptides found in COVID-19 patients, as well as a combination of both in 3D human iPSC-derived neural stem cells differentiated for either 2 weeks (short-term) or 8 weeks (long-term, 2 weeks in suspension + 6 weeks on MEA) towards neurons/glia. Whole transcriptome and qPCR analysis revealed that spike protein and toxin-like peptides at non-cytotoxic concentrations differentially perturb the expression of SPHK1, ELN, GASK1B, HEY1, UTS2, ACE2 and some neuronal-, glia- and NSC-related genes critical during brain development. Additionally, exposure to spike protein caused a decrease of spontaneous electrical activity after two days in long-term differentiated cultures. The perturbations of these neurodevelopmental endpoints are discussed in the context of recent knowledge about the key events described in Adverse Outcome Pathways relevant to COVID-19, gathered in the context of the CIAO project (https://www.ciao-covid.net/).publishersversionpublishe