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Introduction: Hypophosphatasia (HPP) is a rare genetic disease caused by inactivating variants of the ALPL gene. Few data are available on the clinical presentation in Italy and/or on Italian HPP surveys. Methods: There were 30 suspected HPP patients recruited from different Italian tertiary cares. Biological samples and related clinical, biochemical, and anamnestic data were collected and the ALPL gene sequenced. Search for large genomic deletions at the ALPL locus (1p36) was done. Phylogenetic conservation and modeling were applied to infer the effect of the variants on the protein structure. Results: There were 21 ALPL variants and one large genomic deletion found in 20 out of 30 patients. Unexpectedly, NGS-driven differential diagnosis allowed uncovering three hidden additional HPP cases, for a total of 33 HPP subjects. Eight out of 24 coding variants were novel and classified as "pathogenic", "likely pathogenic", and "variants of uncertain significance". Bioinformatic analysis confirmed that all the variants strongly destabilize the homodimer structure. There were 10 cases with low ALP and high VitB6 that resulted negative to genetic testing, whereas two positive cases have an unexpected normal ALP value. No association was evident with other biochemical/clinical parameters. Discussion: We present the survey of HPP Italian patients with the highest ALPL mutation rate so far reported and confirm the complexity of a prompt recognition of the syndrome, mostly for HPP in adults. Low ALP and high VitB6 values are mandatory for the genetic screening, this latter remaining the gold standard not only to confirm the clinical diagnosis but also to make differential diagnosis, to identify carriers, to avoid likely dangerous therapy in unrecognized cases. [ABSTRACT FROM AUTHOR]

Recipes on the composition of the "salad of the monks" (Capuchin monks) have been reported in Italy since the 17th century. Different wild edible plants were highly regarded as an important ingredient of this mixed salad. Among these, some species played a key role for both their taste and nutritional properties: Plantago coronopus L. (PC), Rumex acetosa L., Cichorium intybus L., and Artemisia dracunculus L. In the present study, the micromorphological and phytochemical features as well as the antioxidant and anti-inflammatory properties of extracts of these fresh and blanched leaves, were investigated. The extracts obtained by blanched leaves, according to the traditionally used cooking method, showed the highest content of bioactive compounds (total phenols 1202.31–10,751.88 mg GAE/100 g DW; flavonoids 2921.38–61,141.83 mg QE/100 g DW; flavanols 17.47–685.52 mg CE/100 g DW; proanthocyanidins 2.83–16.33 mg CyE/100 g DW; total chlorophyll 0.84–1.09 mg/g FW; carbohydrates 0.14–1.92 g/100 g FW) and possess the most marked antioxidant (IC50 0.30–425.20 µg/mL) and anti-inflammatory activity (IC50 240.20–970.02 µg/mL). Considering this, our results indicate that increased consumption of the investigated plants, in particular of PC, raw or cooked briefly, could provide a healthy food source in the modern diet by the recovery and enhancement of ancient ingredients. [ABSTRACT FROM AUTHOR]

The phytotoxicity and eco-compatibility of essential oils (EOs) from Eucalyptus gunnii (EG) and E. pulverulenta 'Baby Blue' (EP), cultivated in Italy for their cut foliage, were investigated. Leaf micromorphology, EOs phytochemical characterization, and phytotoxicity were analysed. EP revealed a significantly higher oil gland density and a higher EO yield with respect to EG. In both EOs, 1,8-cineole was the major compound (~75%), followed by α-pinene in EG (13.1%) and eugenol in EP (7.5%). EO phytotoxicity was tested on both weeds (Lolium multiflorum, Portulaca oleracea) and crops (Raphanus sativus, Lactuca sativa, Lepidium sativum, Solanum lycopersicum, Pisum sativum, Cucumis sativus). EG EO inhibited germination of P. oleracea, R. sativus, and S. lycopersicum seeds (ranging from 61.5 to 94.6% for the higher dose used), while affecting only radical elongation in S. lycopersicum (ranging from 66.7 to 82.6%). EP EO inhibited germination of P. oleracea and R. sativus (ranging from 41.3 to 74.7%) and affected radical elongation of L. sativum and L. multiflorum (ranging from 57.4 to 76.0%). None of the EOs affected the germination and radical growing of L. sativa, P. sativum, and C. sativus. Moreover, EP EO was more active than EG EO in inhibiting α-amylase, a key enzyme for seed growth regulation. Brine shrimp lethality assay showed that both EOs are safe for aquatic organisms, suggesting their high eco-compatibility. The data collected provide useful information for future applications of these EOs in agriculture as safe and selective bioherbicides. [ABSTRACT FROM AUTHOR]

Levels of benzo[a]pyrene (BaP) and benzo[a]anthracene (BaA) in “Provola” cheese samples from Calabria, smoked naturally and using commercial smoke-flavouring, have been determined. A comparative study of BaP and BaA concentrations was carried out on rind, exterior zone, core and slice of these samples. Quantitative determination of BaP and BaA was ascertained by HPLC using fluorescence detection. Levels of BaP and BaA were found in all smoked “Provola” cheese samples, but higher in cheese smoked with natural methods (0.46-1.13 µg kg-1 for BaP and 1.38-9.29 µg kg-1 for BaA) compared to samples smoked using commercial flavouring (0.085-0.32 µg kg-1 for BaP and 1.20-2.98 µg kg-1 for BaA). The smoking process contributes to polycyclic aromatic hydrocarbons contamination; however, for improved food safety, the use of commercial buffered smoke is preferable to traditional smoking procedures. [ABSTRACT FROM AUTHOR]

The present investigation was carried out on the bluefin tuna (Thunnus thynnus) collected during the month of April 2003 from the Straits of Messina. The aim of this study is to determine heavy metal levels (Cd, Cu, Hg, Mn, Pb and Zn) in liver and muscle tissues of 14 Thunnus thynnus of different age and sex and to investigate the relationships between fish sex and size (length and weight and metal concentrations in the tissues. The concentrations of the various metals were determined by a Varian atomic absorption spectroscopy instrument. The results showsignificant variations ( p < 0.01) for Hg and Zn concentrations in muscle than in liver samples. Concentrations of Cd and Pb are below the instrumental detection limits in almost all muscle samples. Levels of Hg (3.03 + 0.55 μg/g) are above the MRLs only in muscle (1μg/g) establishing toxicological risks for the consumer. Regression analysis shows a negative correlation between mercury level and weight and length in samples from both female and male. No significant difference between mean heavy metals concentrations and male or female tuna is seen. For greater food safety, it would be advisable to reduce the mercury intake by selecting safer fish, species and size and by the avoidance of tuna fish consumption by pregnant women, young children and old people, who are more sensitive to mercury exposure. [ABSTRACT FROM AUTHOR]

Anaplastic lymphoma kinase (ALK) fusions identify a limited subset of non–small cell lung cancer (NSCLC) patients, whose therapeutic approach have been radically changed in recent years. However, diagnostic procedures and clinical-radiological responses to specific targeted therapies remain heterogeneous and intrinsically resistant or poor responder patients exist. A total of 290 patients with advanced NSCLC defined as ALK+ by immunohistochemistry (IHC) and/or fluorescent in situ hybridisation (FISH) test and treated with single or sequential multiple ALK inhibitors (ALKi) from 2011 to 2017 have been retrospectively retrieved from a multicentre Italian cancer network database. In 55 patients with enough leftover tumour tissue, specimens were analysed with both targeted and customised next generation sequencing panels. Identified fusion variants have been correlated with clinical outcomes. Of the 55 patients, 24 received crizotinib as first-line therapy, 1 received ceritinib, while 30 received chemotherapy. Most of the patients (64%) received ALKi in sequence. An ALK fusion variant was identified in 73% of the cases, being V3 variant (E6A20) the most frequent, followed by V1 (E13A20) and more rare ones (e.g. E6A19). In three specimens, four new EML4-ALK fusion breakpoints have been reported. Neither fusion variants nor brain metastases were significantly associated with overall survival (OS), while it was predictably longer in patients receiving a sequence of ALKi. The presence of V1 variant was associated with progression-free survival (PFS) improvement when crizotinib was used (p = 0.0073), while it did not affect cumulative PFS to multiple ALKi. Outcomes to sequential ALKi administration were not influenced by fusion variants. Nevertheless, in V1+ patients a prolonged clinical benefit was observed. Fusion variant identification by NGS technology may add relevant information about rare chromosomal events that could be potentially correlated to worse outcomes. • NGS platforms add relevant information to refine diagnosis of ALK+ NSCLC patients. • RNA-based technologies allow the identification of rare/unknown EML4-ALK fusions. • Fusion variants correlate with clinical outcomes to single/sequential ALKi. • Molecular stratification of ALK+ patients may inform clinical strategies. [ABSTRACT FROM AUTHOR]

Abstract: Three extracts of different polarities of Glycyrrhiza glabra L. leaves were characterized and evaluated for their antioxidant, anti-genotoxic and anti-inflammatory activity. In total, thirty components have been identified and quantified through the use of liquid chromatography (LC) with ultraviolet-visible diode-array-detector (UV-vis-DAD) and mass spectrometry (MS). The main components belong to the polyphenols family, being flavonoid and dihydrostilbene derivatives. The extracts have been investigated for their antioxidant, anti-genotoxic and anti-inflammatory activities, which are fundamental requirements of efficacious chemo-preventive agents. The ethyl acetate extract proved to be the most valuable, evidently for the conspicuous presence of several polyphenols, namely flavonoids and dihydrostilbenes. [Copyright &y& Elsevier]

Abstract: In this study the presence of residual levels of Polycyclic Aromatic Hydrocarbons (PAHs) in milk samples from Calabria was evaluated. A comparative analysis of PAHs concentrations was conducted on raw, pasteurized, UHT semi-skimmed and whole milk. Quantitative determination of PAHs was performed by HPLC using a fluorescence detector and analysis in HPLC–MS was conducted to confirm the presence of these compounds. Residual levels of PAHs were found in all milk samples analyzed, showing higher concentrations in pasteurized and UHT milk than in raw milk samples. The results obtained demonstrate that PAHs presence also in raw milk is dependent from environmental pollution but pasteurization and UHT treatments of milk can influence PAHs formation; the differences found between whole and semi-skimmed samples can be due to different fat content of milk. [Copyright &y& Elsevier]

Background: The Mediterranean Diet (MedDiet) has long been recognized for its health-promoting attributes, with proven benefits in preventing cardiovascular and metabolic diseases. During the global COVID-19 pandemic, MedDiet's potential to mitigate the impact of SARS-CoV-2 infection gained attention. This study aims to investigate the interplay among MedDiet adherence, immune system response to SARS-CoV-2 vaccines, and potential sex-related variations., Methods: A retrospective observational study was conducted through collecting data from a web survey for the Italian population. Adherence to the MedDiet was assessed using the Mediterranean Diet Adherence Screener (MEDAS); in addition, COVID-19 symptoms and vaccination details were also obtained., Results: Significant associations between MedDiet adherence, COVID-19 symptoms, and vaccine-related side effects were observed. Notably, females demonstrated distinct responses, reporting lymph node enlargement and a different prevalence and severity of vaccine side effects compared to males., Conclusions: This study highlights the protective role of the MedDiet against COVID-19 and emphasizes the relevance of sex-specific responses in vaccination outcomes according to MEDAS score.

The aim of the study was to investigate the micromorphology of Mentha pulegium leaves and flowers harvested in three different Sicilian (Italy) areas with peculiar pedo-climatic conditions, and to characterize the phytochemical profile, the phytotoxic activity, and the eco-compatibility of their essential oils (EOs) for potential use as safe bioherbicides. Light microscopy (LM) and scanning electron microscopy (SEM) highlighted that M. pulegium indumentum consists of non-glandular and glandular trichomes of different types. Peltate trichomes of plants from the different sites showed few significant differences in dimension and abundance, but they were characterized by a surprisingly high number of secretory cells both in leaves and flowers. Phytochemical analyses showed that oxygenated monoterpenes were the most abundant class in all the EOs investigated (92.2-97.7%), but two different chemotypes, pulegone/isomenthone and piperitone/isomenthone, were found. The complex of morphological and phytochemical data indicates that soil salinity strongly affects the expression of the toxic metabolite pulegone, rather than the EO yield. Phytotoxicity tests showed a moderate activity of EOs against the selected species as confirmed by α-amylase assay. Moreover, the low toxicity on brine shrimp provided a rationale for the possible use of investigated EOs as eco-friendly herbicides.

Background: We report the initial results from a phase I clinical trial for ALS. We transplanted GMP-grade, fetal human neural stem cells from natural in utero death (hNSCs) into the anterior horns of the spinal cord to test for the safety of both cells and neurosurgical procedures in these patients. The trial was approved by the Istituto Superiore di Sanità and the competent Ethics Committees and was monitored by an external Safety Board., Methods: Six non-ambulatory patients were treated. Three of them received 3 unilateral hNSCs microinjections into the lumbar cord tract, while the remaining ones received bilateral (n = 3 + 3) microinjections. None manifested severe adverse events related to the treatment, even though nearly 5 times more cells were injected in the patients receiving bilateral implants and a much milder immune-suppression regimen was used as compared to previous trials., Results: No increase of disease progression due to the treatment was observed for up to18 months after surgery. Rather, two patients showed a transitory improvement of the subscore ambulation on the ALS-FRS-R scale (from 1 to 2). A third patient showed improvement of the MRC score for tibialis anterior, which persisted for as long as 7 months. The latter and two additional patients refused PEG and invasive ventilation and died 8 months after surgery due to the progression of respiratory failure. The autopsies confirmed that this was related to the evolution of the disease., Conclusions: We describe a safe cell therapy approach that will allow for the treatment of larger pools of patients for later-phase ALS clinical trials, while warranting good reproducibility. These can now be carried out under more standardized conditions, based on a more homogenous repertoire of clinical grade hNSCs. The use of brain tissue from natural miscarriages eliminates the ethical concerns that may arise from the use of fetal material., Trial Registration: EudraCT:2009-014484-39 .