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The microbiological monitoring of bivalve mollusk harvesting areas in the Marche region is based on the parameters of Escherichia coli and Salmonella spp. However, Regulation EU/2019/627 stated criteria based on E. coli only to determine the health status of these areas. Therefore, the reason for Salmonella spp. monitoring, as provided in the Marche region, could be aimed at reducing the risk of placing on the market contaminated bivalve mollusks. This study, using the results of microbiological monitoring carried out in the Marche region from 2015 to 2022 and the methods based on Bayes' theorem and Poisson’s distribution, evaluated the effectiveness and efficiency of Salmonella spp. monitoring in reducing the risk to the consumer. The results show that i) the use of a single sample unit significantly reduced the possibility of detecting non-compliance with the microbiological safety criterion; ii) the time taken to report positive results (average of approximately 10 days) did not allow the timely implementation of control measures; iii) the prevalence of positive outcomes was quite sporadic: a random trend of positivity is recognizable on a geographical and monthly basis for mussels and a geographical basis for striped clams; iv) considering the predictive value of E. coli against Salmonella spp., the specificity is very high and the negative predictive value versus Salmonella spp. would be >80%. In conclusion, the study shows that the monitoring of Salmonella spp. has a limited effect on reducing the risk to the consumer; however, in the cost/benefit assessment, other aspects not covered by this study should be considered.

Abstract Lagoecia cuminoides L. is a very rare and threatened taxon in Italy, never studied before for its ecology and potential use for human consumption. Furthermore, few data are available on the biological activities of its metabolites. A phytosociological study was carried out in the only two Italian sites, and its state of conservation was also evaluated according to the IUCN (International Union for Conservation of Nature) protocol. The collected plant material was used to make two types of extracts: hot water infusion to evaluate the use of this plant as tea and hydroalcoholic extraction to evaluate the use of it in herbal liqueur preparation. The presence of functional compounds in the extracts were investigated by gas and liquid chromatography coupled to mass spectrometry techniques. Ten non volatiles compounds were identified in the extracts, most of which derivatives of quercetin. Thirty-five volatiles compounds were also identified in the plant aerial part and extracts belonging to the chemical class of terpenoids, and among them β-farnesene, thymol, γ-terpinene and p-cymene were the most abundant. The species is characterized by compounds known for their health effects and for its potential applications for human consumption, being this species already used as decoction in some countries of Middle East. Thanks to its characteristic behaviour to grow in limiting pedoclimatic conditions this species can be potentially used in organic farms situated in rural marginal areas.

Abstract A hyperspectral imaging database was collected on two hundred and five grape plant leaves. Leaves were measured with a hyperspectral camera in the visible/near infrared spectral range under controlled conditions. This dataset contains hyperspectral acquisition of grape leaves of seven different varieties. For each variety, acquisitions were performed on healthy leaves and leaves with foliar symptoms caused by different grapevine diseases showing clear symptoms of biotic or abiotic stress on other organs. For each leaf, chemical measurements such as chlorophyll and flavonol contents were also performed.

Intratumoral immunotherapy strategies for cancer based on interleukin-12 (IL-12)-encoding cDNA and mRNA are under clinical development in combination with anti-PD-(L)1 monoclonal antibodies. To make the most of these approaches, we have constructed chimeric mRNAs encoding single-chain IL-12 fused to single-chain fragment variable (scFv) antibodies that bind to transforming growth factor β (TGF-β) and CD137 (4-1BB). Several neutralizing TGF-β agents and CD137 agonists are also undergoing early-phase clinical trials. To attain TGF-β and CD137 binding by the constructions, we used bispecific tandem scFv antibodies (taFvs) derived from the specific 1D11 and 1D8 monoclonal antibodies (mAbs), respectively. Transfection of mRNAs encoding the chimeric constructs achieved functional expression of the proteins able to act on their targets. Upon mRNA intratumoral injections in the transplantable mouse cancer models CT26, MC38, and B16OVA, potent therapeutic effects were observed following repeated injections into the tumors. Efficacy was dependent on the number of CD8+ T cells able to recognize tumor antigens that infiltrated the malignant tissue. Although the abscopal effects on concomitant uninjected lesions were modest, such distant effects on untreated lesions were markedly increased when combined with systemic PD-1 blockade.

IL-12 is a potent cytokine for cancer immunotherapy. However, its systemic delivery as a recombinant protein has shown unacceptable toxicity in the clinic. Currently, the intratumoral injection of IL-12-encoding mRNA or DNA to avoid such side effects is being evaluated in clinical trials. In this study, we aimed to improve this strategy by further favoring IL-12 tethering to the tumor. We generated in vitro transcribed mRNAs encoding murine single-chain IL-12 fused to diabodies binding to CSF1R and/or PD-L1. These targeted molecules are expressed in the tumor microenvironment, especially on myeloid cells. The binding capacity of chimeric constructs and the bioactivity of IL-12 were demonstrated in vitro and in vivo. Doses as low as 0.5 μg IL-12-encoding mRNA achieved potent antitumor effects in subcutaneously injected B16-OVA and MC38 tumors. Treatment delivery was associated with increases in IL-12p70 and IFN-γ levels in circulation. Fusion of IL-12 to the diabodies exerted comparable efficacy against bilateral tumor models. However, it achieved tethering to myeloid cells infiltrating the tumor, resulting in nearly undetectable systemic levels of IL-12 and IFN-γ. Overall, tethering IL-12 to intratumoral myeloid cells in the mRNA-transferred tumors achieves similar efficacy while reducing the dangerous systemic bioavailability of IL-12.

BACKGROUND: Coronary obstruction following transcatheter aortic valve replacement (TAVR) is a life-threatening complication. For patients at elevated risk, it is not known how valve choice is influenced by clinical and anatomic factors and how outcomes differ between valve platforms. For patients at high risk of coronary obstruction, we sought to describe the anatomical and clinical characteristics of patients treated with both balloon-expandable (BE) and self-expanding (SE) valves. METHODS: This was a multicenter international registry of patients undergoing TAVR who are considered to be at high risk of coronary obstruction and receiving pre-emptive coronary protection. RESULTS: A total of 236 patients were included. Patients receiving SE valves were more likely to undergo valve-in-valve procedures and also had smaller sinuses of Valsalva and valve-to-coronary distance. Three-year cardiac mortality was 21.6% with SE vs 3.7% with BE valves. This was primarily driven by increased rates of definite or probable coronary occlusion, which occurred in 12.1% of patients with SE valves vs 2.1% in patients with BE valves. CONCLUSIONS: In patients undergoing TAVR with coronary protection, those treated with SE valves had increased rates of clinical and anatomic features that increase the risk of coronary obstruction. These include an increased frequency of valve-in-valve procedures, smaller sinuses of Valsalva, and smaller valve-to-coronary distances. These patients were observed to have increased cardiac mortality compared with patients treated with BE valves, but this is likely due to their higher risk clinical and anatomic phenotypes rather than as a function of the valve type itself.

A simple sensor for the quantitation of tryptophan (Trp) has been developed using a glassy carbon electrode (GCE) modified with electro-synthesized carbon dots functionalized with glycine (Gly@CDs). The surface functionalization with an amino acid led to the formation of large clusters of nanostructures. To our knowledge, this is the first study in which a Gly@CDs clusters modified GCE is used for the analysis of Trp. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) are the techniques used to study Trp electrochemical behavior in an alkaline solution using such an electrode. A linear concentration range was found for Trp from 5 × 10−6 to 5 × 10−3 mol L−1 with a detection limit (LOD) of 5 × 10−6 mol L−1. The reproducibility and repeatability data were satisfactory in terms of RSD%. Moreover, the stability during the time of the modified electrode was considered, evidencing interesting results. The described sensor was used for the determination of Trp in herbal tea and a dietary supplement, and the results were compared with those obtained with HPLC-ESI-MS in the Selected Ion Recording (SIR) mode as an independent method. The electrochemical sensor presents significant advantages in terms of low cost, portability, ease of handling and not requiring skilled personnel.

Some olive cultivars grown in southeastern Italy are characterized by the production of olives with a reduced level of bitterness. They are known as sweet olive cultivars and fruits are usually consumed directly or cooked without any debittering process, offering either health benefits to consumers, thanks to the high content of antioxidants, or an economic benefit to farmers for their higher price with respect to both table and oil olives. This study evaluates and compares the organoleptic, pomological, chemical, and physical parameters of seven sweet olive cultivars at different ripening degrees in the Puglia region over 8 weeks of maturity stage for two consecutive seasons (2022 and 2023). The organoleptic evaluation was performed by a restricted panel of usual consumers/experts of sweet olives. The results showed a higher preference for the olive cultivars locally named Triggiano Dolce, Cerasella, and Mele. Significant differences in weight, length, and width of the fruits were observed based on both cultivar and year. The phenolic composition of olive cultivars was significantly affected by both cultivar and harvest year, with Cazzinicchio and Cellina di Nardò having the highest total polyphenols. The analysis of water fraction extracted from olive samples by liquid chromatography coupled with mass spectrometry led to the identification of eleven compounds belonging to the secoiroids, phenylpropanoids, phenylethanolids, and flavonoids classes. The comparison of these compounds among the studied cultivars highlighted significant differences.

Background: Age-related remodelling has the potential to affect the microvascular response to hyperemic stimuli. However, its precise effects on the vasodilatory response to adenosine and contrast medium, as well as its influence on fractional flow reserve (FFR) and contrast fractional flow reserve (cFFR), have not been previously investigated. We investigate the impact of age on these indices. Methods: We extrapolated data from the post-revascularization optimization and physiological evaluation of intermediate lesions using fractional flow reserve (PROPHET-FFR) and The Multi-center Evaluation of the Accuracy of the Contrast MEdium INduced Pd/Pa RaTiO in Predicting (MEMENTO) studies. Only lesions with a relevant vasodilatory response to adenosine and contrast medium were considered of interest. A total of 2080 patients, accounting for 2294 pressure recordings were available for analysis. The cohort was stratified into three age terciles. Age-dependent correlations with FFR, cFFR, distal pressure/aortic pressure (Pd/Pa) and instantaneous wave-free ratio (iFR) were calculated. The vasodilatory response was calculated in 1619 lesions (with both FFR and cFFR) as the difference between resting and hyperaemic pressure ratios and correlated with aging. The prevalence of FFR-cFFR discordance was assessed. Results: Age correlated positively to FFR (r = 0.062, p = 0.006), but not with cFFR (r = 0.024, p = 0.298), Pd/Pa (r = –0.015, p = 0.481) and iFR (r = –0.026, p = 0.648). The hyperemic response to adenosine (r = –0.102, p ≤ 0.0001) and to contrast medium (r = –0.076, p = 0.0023) showed a negative correlation with age. When adjusted for potential confounders, adenosine induced hyperaemia was negatively associated with age (p = 0.04 vs p = 0.08 for cFFR). Discordance decreased across age terciles (14.64% vs 12.72% vs 10.12%, p = 0.032). Conclusions: As compared to adenosine, contrast induced hyperaemia appeared to be less affected by age. cFFR may be considered a more stable and reproducible tool to assess epicardial stenosis in elderly patients. Clinical Trial Registration: PROPHET-FFR STUDY, Clinicaltrials.gov (NCT05056662).

Background: B-lineage acute lymphoblastic leukemias (B-ALL) harboring rearrangements of the histone lysine [K]-Methyltransferase 2A (KMT2A) gene on chromosome 11q23 (KMT2A-r), represent a category with dismal prognosis. The prompt identification of these cases represents an urgent clinical need. Considering the correlation between rat neuron glial-antigen 2 (NG2) chondroitin sulfate proteoglycan molecule expression and KMT2A-r, we aimed identifying an optimized cytofluorimetric diagnostic panel to predict the presence of KMT2A-r. Materials and Methods: We evaluated 88 NG2+ B-ALL cases identified with a NG2 positivity threshold >10%, from a cohort of 1382 newly diagnosed B-ALLs referred to the Division of Hematology of ‘Sapienza’ University of Rome. Results: Eighty-five of 88 (96.6%) NG2+ B-ALLs harbored KMT2A-r and were mainly pro-B ALL (77/85; 91%). Only 2 B-ALLs with KMT2A-r showed NG2 expression below 10%, probably due to the steroid therapy administered prior to cytofluorimetric analysis. When compared to KMT2A-r‒ cases, KMT2A r+ B-ALLs presented a higher blast percentage, a significantly higher mean fluorescence intensity (MFI) of CD45, CD38 and CD58, and a significantly lower CD34, CD22, TdT and CD123 MFI. The differences in CD45, CD34, CD22 and TdT MFI were confirmed within the same immunologic EGIL (European Group for the immunological classification of leukemias) group, suggesting no influence of the B-ALLs EGIL subtype on the peculiar KMT2A-r+ B-ALLs immunophenotype. Conclusions: Our data show how the association between NG2 and KMT2A-r in B-ALLs identify a peculiar immunophenotypic pattern, useful for rapid identification in diagnostic routines of these subtypes of B-ALLs with a poor prognosis, that benefit from a specific therapeutic approach.

IntroductionAddressing the ongoing needs of individuals with diabetes, particularly in low- and middle-income countries like the Philippines, requires a focus on regular follow-ups with healthcare teams, adherence to healthy behaviors, and effective patient education to prevent long-term complications. The aim of this study was to ascertain the impact of a comprehensive educational program for those living with diabetes in the Philippines.MethodsIn a prospective study, a convenience sample of patients living with diabetes attending a cardiac rehabilitation or an outpatient diabetes clinic in the Philippines received a 12-week education intervention. Participants completed surveys at pre- and post-intervention assessing disease-related knowledge, health literacy, dietary habits, and tobacco use. Physical activity was measured by steps taken per day using wearable devices and by self-report of minutes of moderate or vigorous-intensity exercise per week. Satisfaction with the educational materials was also evaluated by a survey composed of Likert-type scale and open-ended questions. Descriptive statistics, paired t-tests or chi-square were used for data analysis.ResultsOverall, 184 individuals living with diabetes type 2 (mean age = 54.4 ± 12.4, 32% female) completed both assessments. There was significant improvement in disease-related knowledge (p

BACKGROUND: L’osteopatia è una modalità di terapia manuale che, attraverso valutazioni dell’equilibrio neurovegetativo e trattamenti di tipo manipolativo, è in grado di individuare le rigidità presenti nel corpo e rimuoverle, in condizioni di salute e malattia. OBIETTIVI: Valutare l’efficacia del trattamento manipolativo osteopatico, in base ai cambiamenti osservati nei parametri vitali, pianto e alimentazione, nel paziente pediatrico affetto da cardiopatia congenita, sottoposto a procedure cardiochirurgiche, aritmologiche ed emodinamiche. METODI: È stato condotto uno studio osservazionale retrospettivo, in cui sono stati inclusi i pazienti sottoposti a procedure cardiochirurgiche, emodinamiche ed aritmologiche, con età compresa tra 0 e 18 anni. I dati sono stati raccolti attraverso la consultazione della documentazione clinica ed infermieristica, per un totale di 120 pazienti, suddivisi in due gruppi: gruppo non trattato (N= 67), sottoposto a nessun trattamento; gruppo trattato (N= 53), che ha ricevuto le cure osteopatiche. I dati sono stati elaborati tramite il programma Excel, i software SPSS versione 24.0 ed R© 3.6.3. RISULTATI: L’analisi dei dati ha evidenziato una variazione assoluta Pre-Post trattamento in due dei parametri vitali considerati, quali la frequenza respiratoria (variazione assoluta di -4,43) e la frequenza cardiaca (variazione assoluta di -6,7), statisticamente significativa in entrambi i casi (p ≤0,002). CONCLUSIONI: Lo studio descritto documenta come la co-terapia osteopatica è associata ad un cambiamento delle condizioni del bambino cardiochirurgico in termini di frequenza respiratoria e cardiaca. Considerando questi risultati, l’osteopatia sembrerebbe essere un supporto efficace della medicina convenzionale nella cura del bambino nel periodo post operatorio.

ABSTRACTPrevious studies have shown that local delivery of tumor antigen-specific CD8+ T lymphocytes engineered to transiently express single-chain IL-12 mRNA is highly efficacious. Peritoneal dissemination of cancer is a frequent and often fatal patient condition usually diagnosed when the tumor burden is too large and hence uncontrollable with current treatment options. In this study, we have modeled intracavitary adoptive T cell therapy with OVA-specific OT-I T cells electroporated with IL-12 mRNA to treat B16-OVA and PANC02-OVA tumor spread in the peritoneal cavity. Tumor localization in the omentum and the effects of local T-cell encounter with the tumor antigens were monitored, the gene expression profile evaluated, and the phenotypic reprogramming of several immune subsets was characterized. Intraperitoneal administration of T cells promoted homing to the omentum more effectively than intravenous administration. Transient IL-12 expression was responsible for a favorable reprogramming of the tumor immune microenvironment, longer persistence of transferred T lymphocytes in vivo, and the development of immunity to endogenous antigens following primary tumor eradication. The efficacy of the strategy was at least in part recapitulated with the adoptive transfer of lower affinity transgenic TCR-bearing PMEL-1 T lymphocytes to treat the aggressive intraperitoneally disseminated B16-F10 tumor. Locoregional adoptive transfer of transiently IL-12-armored T cells appears to offer promising therapeutic advantages in terms of anti-tumor efficacy to treat peritoneal carcinomatosis.

The incidence of type 1 diabetes (T1D) has increased by about 3% per year over the last two decades. Continuous Insulin Subcutaneous Therapy (CSII) is widely used in the pediatric population with diabetes; however, it requires more preparation by the treating team and a careful selection of its potential users. Prescriptive provisions vary from region to region, and the perspective of health workers in this regard remains an unexplored area. The aim of this research project is to explore the representations of a group of diabetologists and psychologists working in pediatric diabetology throughout the country, regarding their roles, functions, and activities as part of a multidisciplinary team; it also aims to investigate their views on the potential benefits of CSII and the types of individuals who apply for the use of this technology. A socio-anagraphic data sheet was administered, and two homogeneous focus groups were conducted, one for each profession, which were then audio recorded. The transcripts produced were analyzed using the Emotional Text Mining (ETM) methodology. Each of the two corpora generated three clusters and two factors. For diabetologists, a focus on patient care emerged at different levels, involving collaboration with other health professionals and engagement with the community, often incorporating technology in medical interventions. Similarly, psychologists’ representations highlighted interdisciplinary networking with a stronger emphasis on the psychological processes involved in managing the disease, from acceptance to the elaboration and integration of diabetes into the family narrative. Understanding the representations of health professionals working in pediatric diabetes with new technologies can contribute to the consolidation of a network of professionals through targeted work on possible critical issues that may arise.