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Introduction Following pivotal trials, real-world evidence is important to assess the impact of new drugs in everyday clinical practice. The RESTORE-1 study aimed to compare effectiveness and safety of the second-generation basal insulins (2BI), i.e., insulin glargine 300 U/ml (Gla-300) vs. degludec 100 U/ml (IDeg-100), in type 1 diabetes (T1D). Methods Retrospective, non-inferiority, multicenter study, based on electronic medical records. All patients switching to Gla-300 or IDeg-100 from first-generation basal insulins (1BI) were 1:1 propensity score matched (PSM). Changes during 6 months in HbA1c (primary endpoint), fasting plasma glucose (FPG), body weight, and insulin doses were assessed using linear mixed models for repeated measures. Incidence rates (IR) of hypoglycemic events were assessed. Results Overall, 19 centers provided data on 585 patients in each PSM cohort. For both groups, statistically significant reductions in HbA1c from baseline to 6 months were documented: − 0.20%; (95% CI − 0.32; − 0.08) in the Gla-300 group and − 0.14%; (95% CI − 0.24; − 0.04) in the IDeg-100 group. The non-inferiority of Gla-300 vs. IDeg-100 was confirmed (non-inferiority margin of 0.30%; upper 95% CI at 6 months, 0.09%). No statistically significant between-group differences emerged in FPG and body weight. Dose changes of basal and short-acting insulin were small in both groups, but higher in the Gla-300 group than in the Deg-100 group (p

Microbial biofilms represent a constant source of contamination in the food industry, being also a real threat for human health. In fact, most of biofilm-producing bacteria are becoming resistant to sanitizers, thus arousing the interest in natural alternatives to prevent biofilm formation on foods and food-contact surfaces. In particular, studies on biofilm control by essential oils (EOs) application are increasing, being EOs characterized by unique mixtures of compounds able to impair the mechanisms of biofilm development. This review reports the anti-biofilm properties of EOs in bacterial biofilm control (inhibition, removal and prevention of biofilm dispersion) on food-contact surfaces. The relationship between EOs effect and composition, concentration, involved bacteria, and surfaces is discussed, and the possible sites of action are also elucidated. The findings prove the high biofilm controlling capability of EOs through the regulation of genes and proteins implicated in motility, Quorum Sensing and exopolysaccharides (EPS) matrix. Moreover, incorporation in nanosized delivery systems, formulation of blends and combination of EOs with other strategies can increase their anti-biofilm activity. This review provides an overview of the current knowledge of the EOs effectiveness in controlling bacterial biofilm on food-contact surfaces, providing valuable information for improving EOs use as sanitizers in food industries.

Data on second generation basal insulin (2BI) in people with type 2 diabetes (T2D) generated by clinical trials still need confirmation in real-world clinical settings. This study aimed at assessing the comparative effectiveness of 2BI [Glargine 300 U/mL (Gla-300) vs. Degludec 100 U/mL (Deg-100)] in T2D Italian patients switching from first generation basal insulins (1BI).This was a retrospective, non-inferiority, multicenter study. Patients switching to Gla-300 or Deg-100 from 1BI were 1:1 propensity score matched (PSM). Changes during 6 months in continuous endpoints were assessed through linear mixed models. Incidence rates (IR) of hypoglycemia (episodes per patient-months) were compared using Poisson regression. Each PSM cohort included 593 patients. HbA1c decreased from baseline (8.7%) to 6 months by -0.58% (95%CI -0.69;-0.47) in Gla-300 group and -0.50% (95%CI -0.61;-0.39) in Deg-100 group, confirming the non-inferiority of Gla-300 vs. Deg-100. No between-group differences emerged: FBG was reduced by about 20 mg/dl with both 2BI, mean dose of 2BI (24.5 U, 0.3 U/Kg at the first prescription) was suboptimally titrated during 6 months (+1.34 U in Gla-300 and + 1.76 U in Deg-100), body weight showed minor changes. IR of hypoglycemia54 mg/dl was 0.32 (95%CI 0.21; 0.49) in Gla-300 group and 0.19 (95%CI 0.11; 0.33) in Deg-100 group (p = 0.14).In subjects with T2D, switching to 2BI from 1BI was associated with similar improvements in glycemic control, low hypoglycemia rates and no weight gain in real-life setting. Clinical inertia, represented by late treatment intensification and suboptimal titration, represents a major issue in Italy.

In this work, we determined the degree of filamentous fungi contamination in cocoa fermented seeds and the fungal potential to produce enzymes that could contribute to the cocoa quality. Internal transcribed spacer amplicon sequencing (ITS) showed 11 different species with Byssochlamys spectabilis, Aspergillus niger, Aspergillus flavus, Aspergillus carbonarius, Circinella muscae and Penicillium citrinum as the most abundant species. Our results evidenced intra and inter-species differences in the enzymes production. Cellulases, β-glucosidase, ornithine decarboxylase and phenylalanine decarboxylase were the most diffused enzymes expressed in the 53 strains here studied. Moreover, A. niger (6/12), A. carbonarius (2/3), and P. citrinum (3/3) showed high pectinolytic activity. Remarkable was the amino decarboxylase activity of P. citrinum, and A. flavus strains. For the first time we reported the presence of B. spectabilis in cocoa fermented beans, which could play an important role in the biogenic amines formation. In addition, we explored the capability of the Aspergillus section Nigri strains, to produce ochratoxin A (OTA) in a cacao model system (CPMS) and in malt extract medium (MEL). We observed that CPMS, but not MEL, stimulated the OTA production in 6 out 15 strains of Aspergillus section Nigri, reaching values ranging between 1.70 and 4995 μg OTA kg

Understanding the bacterial behavior in response to sublethal stresses is crucial for the optimization of antimicrobial treatments, particularly in food processing. However, the data regarding the effect of sublethal concentrations of essential oils (EOs) on microbial cells are still scarce. In this study, we evaluated the response of Listeria monocytogenes ATCC 7644 to the sublethal concentration of 1.25 μL/mL Origanum vulgare L. EO at 30 °C for 1 h, by means of Phenotype Microarray, modelling the kinetic data obtained by inoculating the control and treated cells into GEN III microplates (Biolog Inc.) for 96 h after EO removal. The results showed important differences regarding the growth dynamics in the presence of carbohydrates and environmental conditions often encountered in food products and that normally sustain the growth of the pathogen (i.e. pH 6.0, pH 5.0, NaCl 1–8%, presence of lactic acid and sodium lactate). In detail, the lag phase of the treated cells was extended, the growth rate was slowed down and the maximum concentration was often significantly reduced. Interestingly, the susceptibility to antimicrobials such as vancomycin, lincomycin and rifamycin was restored after EO application and removal, suggesting a potential role in combating antibiotic resistance. Confocal laser scanner microscopy showed a diffuse aggregation of the treated cells, as a response to the stress encountered. In conclusion, a single exposure to a sublethal concentration of O. vulgare EO causes a stressing effect that persists after its removal. This outcome should be better investigated for potential applications both in food production, to combine low EO concentrations with other hurdles to guarantee food safety, and in medicine, to restore the sensitivity to antibiotics.

Aims This study aimed to evaluate the effectiveness of selected essential oils (EOs) and hydrolates (Hs) against Listeria monocytogenes biofilms on polystyrene (PS) and stainless steel (SS) surfaces. Methods and Results Among others, Origanum hirtum EO, Corydothymus capitatus EO and Citrus aurantium H were selected to treat L. monocytogenes biofilms during and after biofilm formation. Sub-minimum inhibitory concentrations (MICs) of C. capitatus EO (0.31 µl/ml) showed the highest inhibiting effect against biofilm formation on PS, while on SS no significant differences between the EOs were observed (43.7%–88.7% inhibition). Overall, the tested biosanitizers showed limited activity as biofilm removal agents. Although generally less effective, C. aurantium H exhibited good biofilm inhibition performance at 62.5 µl/ml, particularly on PS. Confocal laser scanning microscopy proved that sub-MICs of the biosanitizers drastically changed L. monocytogenes biofilm architecture, with bacterial cells elongation in the presence of C. capitatus EO. Conclusions Our findings suggest that the tested EOs and H are able to control Listeria biofilms, particularly preventing biofilm formation on both materials. Considering its mild aroma and hydrophilicity, the H exhibited promising perspectives of application. Significance and Impact of Study This study raises the possibility of applying EOs and Hs to control biofilms on different surfaces in the food industry.

Made available in DSpace on 2022-05-01T12:09:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 Using UAV and multispectral images has contributed to identifying field variability and improving crop management through different data modeling methods. However, knowledge on application of these tools to manage peanut maturity variability is still lacking. Therefore, the objective of this study was to compare and validate linear and multiple linear regression with models using artificial neural networks (ANN) for estimating peanut maturity under irrigated and rainfed conditions. The models were trained (80% dataset) and tested (20% dataset) using results from the 2018 and 2019 growing seasons from irrigated and rainfed fields. In each field, plant reflectance was collected weekly from 90 days after planting using a UAV-mounted multispectral camera. Images were used to develop vegetation indices (VIs). Peanut pods were collected on the same dates as the UAV flights for maturity assessment using the peanut maturity index (PMI). The precision and accuracy of the linear models to estimate PMI using VIs were, in general, greater in irrigated fields with R2 > 0.40 than in rainfed areas, which had a maximum R2 value of 0.21. Multiple linear regressions combining adjusted growing degree days (aGDD) and VIs resulted in decreased RMSE for both irrigated and rainfed conditions and increased R2 in irrigated areas. However, these models did not perform successfully in the test process. On the other hand, ANN models that included VIs and aGDD showed accuracy of R2 = 0.91 in irrigated areas, regardless of using Multilayer Perceptron (MLP, RMSE = 0.062) or Radial Basis Function (RBF, RMSE = 0.065), as well as low tendency (1:1 line). These results indicated that, regardless of the ANN architecture used to predict complex and nonlinear variables, peanut maturity can be estimated accurately through models with multiple inputs using VIs and aGDD. Although the accuracy of the MLP or RBF models for irrigated and rainfed areas separately was high, the overall ANN models using both irrigated and rainfed areas can be used to predict peanut maturity with the same precision. Department of Agriculture School of Agricultural Sciences of Lavras Federal University of Lavras (UFLA), Lavras Department of Crop & Soil Sciences University of Georgia (UGA) Crop Soil and Environmental Sciences Auburn University Department of Engineering and Mathematical Sciences School of Veterinarian and Agricultural Sciences São Paulo State University (UNESP), Jaboticabal Department of Engineering and Mathematical Sciences School of Veterinarian and Agricultural Sciences São Paulo State University (UNESP), Jaboticabal

Francesco Raggi,1 Chiara Rossi,1 Francesco Faita,2 Mariarosaria Distaso,1 Claudia Kusmic,2 Anna Solini1 1Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy; 2Institute of Clinical Physiology, Italian National Research Council, Pisa, ItalyCorrespondence: Anna Solini; Francesco Raggi, Department of Surgical Medical Molecular and Critical Area Pathology, University of Pisa, Via Roma 67, Pisa, I-56126, Italy, Tel +39-50-993482 ; +39-50-992861, Fax +39-50-553235, Email anna.solini@med.unipi.it; francesco.raggi@unipi.itPurpose: Low-grade inflammation contributes to heart failure in obesity or type 2 diabetes mellitus. The P2X7 receptor (P2X7R) is a key regulator of several pro-inflammatory responses in multiple tissues and organs; however, its involvement in the onset of heart dysfunction remains unclear. The study evaluated the role of P2X7R as a cardiac function regulator in C57BL/6J wild-type (WT) and P2X7R knockout (KO) mice by inducing systemic inflammation with high fat diet (HFD).Methods: Specific parameters of systolic and diastolic function and heart morphology were measured in vivo before animal sacrifice by high-frequency ultrasonographic analysis. Gene and protein expression of cardiac biomarkers associated with inflammatory-oxidative pathways were evaluated by real-time PCR and Western Blotting.Results: P2X7R-mediated up-regulation of the NLRP3-caspase-1 complex, increased expression of key oxidative stress (NOS-2, TNFα), and chemotactic (MCP-1) mediators were revealed in WT-HFD animals. In KO-HFD mice, such inflammatory-oxidative pathway was silent. Nevertheless, HFD induced in vivo a clear alteration of diastolic pattern (E/A: p < 0.03 vs WT-HFD) and a cardiac morphologic remodelling (left ventricular mass: p < 0.05 vs WT-HFD) only in P2X7R KO animals. Surprisingly, the transcriptional and protein expression of IL-1β and IL-6, usually regulated through P2X7R activation, were significantly higher in KO-HFD than in WT-HFD mice (both p < 0.05). Furthermore, an up-regulation of miR-214 and a down-regulation of miR-126 in heart of HFD-KO mice were observed, suggesting a link between such epigenetic dysregulation and cytokine overexpression as a potential pathophysiologic mechanism concurring to the progressive cardiac dysfunction.Conclusion: These findings seem to suggest a cardioprotective role of P2X7R toward this tissue-specific inflammatory damage, likely through tissue homeostasis and organ functionality preservation.Keywords: low-grade inflammation, high fat diet, diastolic dysfunction, P2X7 receptor

Introduction Primary aim was to provide real-world evidence of the outcomes after the switch to glargine 300 U/ml (Gla-300) from other basal insulins (first or second generation) in Italy. Methods Multicenter, observational, retrospective study based on electronic medical records. Results Overall, 953 T2DM insulin ± OAD treated people switched to Gla-300 or Gla-100 from January 2015 to July 2018. Three clinically relevant cohorts were identified: patients switching to Gla-300 from first-generation basal insulin (cohort 1), patients switching to Gla-300 from degludec-100 (Deg-100) (cohort 2), and those switching to Gla-100 from any basal insulin (cohort 3). The three cohorts differed in terms of age, diabetes duration, and metabolic control. HbA1c changes after 6 months from the switch were − 0.27% (95% CI − 0.38; − 0.16), − 0.06% (95% CI − 0.31; 0.19), and − 0.30% (95% CI − 0.51; − 0.09) in the three cohorts, respectively. FPG significantly decreased in cohort 1 (− 14.07 mg/dl, 95% CI − 20.25; − 7.89), while body weight significantly decreased in cohort 2 (− 1.47 kg, 95% CI − 2.55; − 0.39). Doses of insulin marginally changed during the follow-up (+ 0.89 U in basal insulin daily dose in cohort 1 and + 2.07 U in short-acting insulin daily dose in cohort 2). Conclusions Switching to Gla-300 from first-generation basal insulin in the real world is associated with improvements in metabolic control despite a suboptimal titration of both basal and short-acting insulins. Inertia in insulin titration documented in the Gla-100 cohort is also observed with the second-generation basal insulin. The switch to Gla-300 from Deg-100 was associated with a decrease in body weight of − 1.47 kg despite a slight increase in short-acting insulin daily doses of about + 2 U.

We present SPICE simulations of a CMOS APS pixel element consisting of the optical sensor with the sensing circuit. The photodiode is simulated at the physics level by means of the so-called Generalized Devices, without any predefined compact model. Conversely, regular compact models are used for MOSFETs present in the circuit. Modeling with Generalized Devices takes into account in SPICE simulations both the layout and the physics of the photodiode, i.e., drift-diffusion transport, optical generation and recombination of excess carriers, capacitive effects and surface recombination. Moreover, electrical coupling between two adjacent pixels, i.e., the electrical crosstalk, is well predicted by the network of Generalized Devices. This approach is supported by TCAD Sentaurus simulations and opens the way to full SPICE simulation of Active Pixel Sensor from the circuit down to the semiconductor level within the same circuit simulation tool.

Background and aim: The study aims at identifying the antecedents and consequences of emotional exhaustion in health professionals and, particularly, examining the process that leads from a hindrance demand, like role ambiguity, to exhaustion and job satisfaction. Emotional exhaustion is a phenomenon that affect health professionals with negative consequence on job satisfaction, and literature has underlined that job demands could be may be a cause of this chronic stress. However, the relationship among job demands, work engagement and exhaustion has produced results not always converging. Method: A self-report questionnaire was administered to 66 health professionals. Results: The results showed that the effect of role ambiguity on emotional exhaustion was mediated by work engagement and the emotional exhaustion impairs job satisfaction when workers are not committed to their profession. Conclusions: Role ambiguity represents a psychosocial risk factor that influence workers’ wellbeing diminishing the level of motivation and this process leads to emotional exhaustion. However, professional commitment appears to be a resource that can protect professionals preventing a decrease in satisfaction. These findings suggest that human resource management should remove hindrance stressors and enhance the mission of Healthcare Professionals in order to increase employees’ work engagement and prevent exhaustion. (www.actabiomedica.it)

Introduction Real-world evidence on the effectiveness and safety of insulin degludec (IDeg) in patients with diabetes is a priority. We have therefore evaluated the effectiveness and safety of IDeg, including impact on metabolic control, glycemic variability, weight gain and hypoglycemia, in patients with type 1 diabetes under routine clinical practice conditions. Methods This was an observational longitudinal multicenter study. A retrospective chart review of all patients with type 1 diabetes who were switched from basal insulin to IDeg was performed, and temporal trends in clinical outcomes were assessed. Results Data obtained from 195 patients, with a median age of 42.8 [interquartile range (IQR) 24.6–56.4] years and a median diabetes duration of 16 (IQR 10.0–28) years, were analyzed. Median follow-up was 9.5 (IQR 7.7–11.3) months. Improvements were found in glycated hemoglobin (− 0.34%; p

MG53 is a myokine modulating insulin signaling in several tissues; its relationship to glucose tolerance or risk of developing type 2 diabetes mellitus (T2DM) is unknown. This observational, prospective study aimed at evaluating the relationship between MG53 and glucose tolerance, testing whether its circulating levels may be associated with disease progression in a cohort at high risk of T2DM.Five hundred and fifteen subjects who underwent a deep characterization of their glucose tolerance in the years 2003-2005 participated in this study. MG53 levels were measured at baseline. Glucose tolerance status was available over a follow-up of 15 ± 2 years for 283 of them; their vital status as of December 2020 was also retrieved.MG53 levels were significantly lower in subjects with normal glucose tolerance than in subjects with impaired glucose regulation (IGR) or T2DM. Individuals in the highest MG53 levels quartile had more frequently 1h-post load glucose ≥ 155 mg/dL (54% vs 39%; p = 0.015), worse proportional control of β-cell function (p 0.05-0.01), as determined by mathematical modeling, and worse Disposition Index (DI) (0.0155 ± 0.0081 vs 0.0277 ± 0.0030; p 0.0001). At follow-up, baseline MG53 levels were higher in progressors than in non-progressors (120.1 ± 76.7 vs 72.7 ± 63.2 pg/ml; p = 0.001; ROC curve area for incident diabetes of 0.704). In a multivariable regression with classic risk factors for T2DM and DI, MG53 remained independently associated with progression with T2DM.MG53 may be a novel biomarker of glucose dysregulation associated with β-cell dysfunction, likely improving our ability to identify, among high-risk subjects, those more likely to develop T2DM.

The process in which locally confined epithelial malignancies progressively evolve into invasive cancers is often promoted by unjamming, a phase transition from a solid-like to a liquid-like state that occurs in various tissues. Whether this tissue-level mechanical transition impact phenotypes during carcinoma progression remains unclear. We show, here that the large fluctuations in cell density that accompany unjamming result in repeated mechanical deformations of cells and nuclei. Cells react to these protracted mechanical stresses by mounting a mechano-protective response that includes enlarged nuclear size and rigidity, altered heterochromatin distribution, and the remodeling of the perinuclear actin architecture into actin rings. The chronic strains and stresses associated with unjamming together with reduction of Lamin B1 levels eventually result in DNA damage and nuclear envelope ruptures, with the release of cytosolic DNA that activates a cGAS/STING-dependent cytosolic DNA response gene program. This mechanically-driven transcriptional rewiring ultimately results in a change in cell state, with the emergence of malignant traits, including epithelial-to-mesenchymal plasticity phenotypes and chemo-resistance in invasive breast carcinoma. One-Sentence Summary: A solid-to-fluid phase transition promotes a pro-inflammatory transcriptional response in invasive breast carcinoma

Aims The European Society of Cardiology (ESC) recently defined cardiovascular risk classes for subjects with diabetes. Aim of this study was to explore the distribution of subjects with type 1 diabetes (T1D) by cardiovascular risk groups according to the ESC classification and to describe the quality indicators of care. Methods The study is based on data extracted from electronic medical records of patients treated at the 258 Italian diabetes centers participating in the AMD (Associazione Medici Diabetologi) Annals initiative. Patients with T1D were stratified by cardiovascular risk. Measures of intermediate outcomes, intensity/appropriateness of pharmacological treatment, and overall quality of care were evaluated. Results Overall, 29.368 subjects with type 1 diabetes (64.7% at very high cardiovascular risk, 28.5% at high risk and 6.8% at moderate risk) were evaluated. A lack of use of drugs in case of high values and an inadequate control despite the antihypertensive and lipid-lowering treatment was recognized. The overall quality of care tended to be lower as the level of cardiovascular risk increased. Conclusion A large proportion of subjects with T1D is at high or very high risk. Antihypertensive and lipid-lowering treatment seem not adequately used. Several actions are necessary to improve the quality of care.

Photo-oxidation of casein proteins is commonplace during milk processing and storage. A major consequence of such light exposure is protein cross-linking and aggregation. Although caseins are key milk components, the nature of the cross-links and the mechanisms involved are poorly characterized, with most previous work having been focused on detecting and quantifying di-tyrosine formed on dimerization of two tyrosine-derived phenoxyl radicals. However, this is only one of a large number of possible cross-links that might be formed. In this study, we have investigated the potential involvement of secondary reactions between oxidized protein side-chains and the thiol group of cysteine (Cys) residues in casein cross-linking. Casein proteins were subjected to photo-oxidation using visible light in the presence of a sensitizer (riboflavin or rose Bengal) and O2, then incubated with a Cys-containing peptide (glutathione, GSH) or protein (κ-casein), and subsequently analyzed by SDS-PAGE, immunoblotting and LC-MS. Our data indicate that that photo-oxidized (but not parent) caseins react efficiently with the Cys-containing species, likely via Michael addition to quinones formed from tyrosine residues to give glutathionylated species or protein adducts. Thus, oxidized α-casein reacts with native κ-casein to give high molecular mass aggregates. This adduct formation was prevented by alkylation of the Cys thiol group. The cross-link site and the residues involved have been confirmed by liquid chromatography-mass spectrometry (LC-MS) proteomic analysis. Together, these data extend our knowledge of the mechanisms involved in casein oxidation and aggregation.

To construct predictive models of diabetes complications (DCs) by big data machine learning, based on electronic medical records.Six groups of DCs were considered: eye complications, cardiovascular, cerebrovascular, and peripheral vascular disease, nephropathy, diabetic neuropathy. A supervised, tree-based learning approach (XGBoost) was used to predict the onset of each complication within 5 years (task 1). Furthermore, a separate prediction for early (within 2 years) and late (3-5 years) onset of complication (task 2) was performed. A dataset of 147.664 patients seen during 15 years by 23 centers was used. External validation was performed in five additional centers. Models were evaluated by considering accuracy, sensitivity, specificity, and area under the ROC curve (AUC).For all DCs considered, the predictive models in task 1 showed an accuracy 70 %, and AUC largely exceeded 0.80, reaching 0.97 for nephropathy. For task 2, all predictive models showed an accuracy 70 % and an AUC 0.85. Sensitivity in predicting the early occurrence of the complication ranged between 83.2 % (peripheral vascular disease) and 88.5 % (nephropathy).Machine learning approach offers the opportunity to identify patients at greater risk of complications. This can help overcoming clinical inertia and improving the quality of diabetes care.

Introduction. Gdue is a nutraceutical obtained from the association of two marine algae, Ascophyllum nodosum and Fucus vesiculosus, in addition to chromium picolinate, which could be useful for the treatment of dysglycemia, overweight, and the other components of the metabolic syndrome. The aim of the study was to assess the real-world effectiveness and safety of Gdue when administered to subjects with one or more components of the metabolic syndrome. Methods. A longitudinal, retrospective, observational study, conducted among primary care physicians, nutritionists, and specialists from various disciplines. The impact of 180 days of administration of Gdue was assessed on body weight, waist circumference, fasting blood glucose, HbA1c, lipid profile, and blood pressure levels. The likelihood of experiencing a first major cardiovascular event over ten years was estimated using Italian risk charts. General linear models for repeated measures were applied to assess changes in the parameters of interest during the follow-up. Results are expressed as estimated marginal means with their 95% confidence interval. Results. Overall, 505 patients were enrolled by 282 physicians. After 6 months of treatment with Gdue, body weight was reduced on average by 7.3 kg (-8.0; -6.6), waist circumference by 7.5 cm (-8.2; -6.8), fasting blood glucose by 16.3 mg/dL (-17.8; -14.7), HbA1c by 0.55% (-0.62; -0.49), systolic and diastolic blood pressure by 7.1 mmHg (-8.3; -6.0) and 4.2 mmHg (-5.0; -3.5), respectively, LDL cholesterol by 18.2 mg/dL (-21.2; -15.3), and triglycerides by 39 mg/dL (-45; -32). HDL cholesterol was significantly increased by 2.9 mg/dL (0.7; 5.0). The 10-year risk of cardiovascular events significantly decreased by 1.8%, corresponding to a relative risk reduction of 27.7%. Conclusion. Our real-world study shows that 6 months of treatment with Gdue have an impact on all the components of the metabolic syndrome, thus offering the potential for decreasing the cardiovascular risk associated with metabolic syndrome.

Randomized clinical trials (RCT) showed benefits of FRC of basal insulin (BI) and GLP1-RAs in terms of glycemic target, no weight gain, low risk of hypoglycemia, and gastrointestinal side effects. Real-world evidence (RWE) complements RCT to assess effectiveness and safety of drugs in clinical practice. The study evaluated the impact of iGlarLixi [once-daily FRC of basal insulin glargine 100 U/mL and GLP1-RA lixisenatide] in T2D. This was a retrospective, multicenter study, based on electronic medical records. All subjects initiating iGlarLixi in May 2018-July 2020 were analyzed. Overall, 25 centers provided data on 675 subjects with the following baseline characteristics (mean and standard deviation or proportion): age: 66.4±10.1 years, 54.2% men, T2DM duration 15.5±11.5 years, HbA1c 8.6±1.4%, and BMI 30.8±5.3 Kg/m2. Before starting iGlarLixi, 67.3% of subjects were treated with BI and 9.9% with GLP1-RA (5.5% as free combinations). Drugs associated with iGlarLixi were not only metformin and SGLT2 inhibitors, as by summary of product characteristics (SmPC); off-label combinations were found in 32.4% of patients (21.4% sulphonylureas). Effectiveness data (N=184) showed that HbA1c decreased by -0.77% [95%CI -1.00;-0.54] after 6 months and by -0.92% [95%CI -1.22;-0.62] in patients treated as by SmPC. Weight significantly decreased by 1.21 Kg. iGlarLixi dose increased by 5.14 U. Rates of blood glucose ≤70 and Disclosure R. Candido: None. M. Modugno: None. E. Gabellieri: None. A. Nicolucci: Advisory Panel; Self; AstraZeneca, Research Support; Self; Novo Nordisk, Pikdare, Sanofi, Shionogi & Co., Ltd., SOBI. M. Rossi: Research Support; Self; Novo Nordisk, Sanofi, Shionogi & Co., Ltd., Swedish Orphan Biovitrum AB. M. Larosa: Employee; Self; Sanofi. On behalf of ensure study group: n/a. Funding Sanofi

Second generation basal insulin (2BI) provide similar/improved efficacy with better safety compared to first generation BI. Real-world data on 2BI in patients with type 2 diabetes (T2D) are still limited. The study aimed at comparing effectiveness of 2BI (Gla-300 vs. iDeg-100) in insulin-naïve T2D. This was a retrospective, non-inferiority, multicenter study, from electronic medical records. All patients initiating Gla-300 or iDeg-100 in January 2017-2020 were 1:1 propensity score matched. Linear mixed models for repeated measures were applied to assess changes during 6 months in HbA1c, fasting blood glucose (FBG), body weight, and insulin doses. Incidence rates (IR) of hypoglycemic events were compared using Poisson regression models. Overall, 19 centers provided data on 357 patients in each PSM cohort. Estimated mean baseline levels of HbA1c were 9.2%. Marked reductions in HbA1c after 6 months were documented: -1.70%; (95%CI -1.90; -1.50) in Gla-300 group and -1.69%; (95%CI -1.89; -1.49) in IDeg-100 group (between group mean difference: 0.01; 95%CI -0.29; 0.27), confirming non-inferiority of Gla-300 vs. IDeg-100. FBG was reduced by about 60 mg/dl in both groups; minor changes in body weight were documented. In both groups, the mean prescribed dose was about 12 U (0.15 U/Kg) and was slightly titrated during 6 months up to +4U (0.20 U/Kg). IR (episodes per patient-months) of BG≤70 mg/dl was 0.13 (95%CI 0.07;0.26) in Gla-300 group and 0.14 (95%CI 0.07;0.27) in IDeg-100 group (p=0.87). IR of BG Disclosure G. Fadini: Board Member; Self; Novo Nordisk, Sanofi, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk, Sanofi. R. Buzzetti: None. A. Nicolucci: Advisory Panel; Self; AstraZeneca, Research Support; Self; Novo Nordisk, Pikdare, Sanofi, Shionogi & Co., Ltd., SOBI. M. Rossi: Research Support; Self; Novo Nordisk, Sanofi, Shionogi & Co., Ltd., Swedish Orphan Biovitrum AB. M. Larosa: Employee; Self; Sanofi. D. Cucinotta: None. On behalf of restore-2 study group: n/a. Funding Sanofi

The picornavirus named ‘Ljungan virus’ (LV, species Parechovirus B) has been detected in a dozen small mammal species from across Europe, but detailed information on its genetic diversity and host specificity is lacking. Here, we analyze the evolutionary relationships of LV variants circulating in free-living mammal populations by comparing the phylogenetics of the VP1 region (encoding the capsid protein and associated with LV serotype) and the 3Dpol region (encoding the RNA polymerase) from 24 LV RNA-positive animals and a fragment of the 5′ untranslated region (UTR) sequence (used for defining strains) in sympatric small mammals. We define three new VP1 genotypes: two in bank voles (Myodes glareolus) (genotype 8 from Finland, Sweden, France, and Italy, and genotype 9 from France and Italy) and one in field voles (Microtus arvalis) (genotype 7 from Finland). There are several other indications that LV variants are host-specific, at least in parts of their range. Our results suggest that LV evolution is rapid, ongoing and affected by genetic drift, purifying selection, spillover and host evolutionary history. Although recent studies suggest that LV does not have zoonotic potential, its widespread geographical and host distribution in natural populations of well-characterized small mammals could make it useful as a model for studying RNA virus evolution and transmission.

BACKGROUND AND PURPOSE Neuroinflammation and probably systemic inflammation, with abnormal α-synuclein deposition, participate in the development of Parkinson's disease (PD). The P2X7 receptor/NLRP3 inflammasome complex is upregulated in the brain of PD patients. By a prospective approach, the degree of systemic activation of such complex, and its regulatory mechanisms, were explored in treatment-naive PD individuals. METHODS The expression and functional activity of the inflammasome were measured in peripheral blood mononuclear cells of 25 newly diagnosed PD patients and 25 controls at baseline and after 12 months of pharmacological treatment, exploring the intracellular signalling involved and its epigenetic regulation. RESULTS De novo PD patients were characterized by a systemic hyper-expression of the P2X7R/NLRP3 inflammasome platform, probably able to modulate lymphomonocyte α-synuclein, whose brain deposits represent the main pathogenetic factor of PD. A reduced c-Jun N-terminal kinase (JNK) phosphorylation might be the intracellular signalling mediating this effect. miR-7 and miR-30, implied in the pathogenesis of PD and in the post-transcriptional control of α-synuclein and NLRP3 expression, were also increased in PD. After 1 year of usual anti-Parkinson treatments, such inflammatory platform was significantly reduced. CONCLUSIONS Mononuclear cells of newly diagnosed PD subjects display a hyper-expression of the P2X7R/NLRP3 inflammasome platform that seems to modulate cellular α-synuclein content and is reduced after PD treatment; an impaired JNK phosphorylation might be the intracellular signalling mediating this effect, undergoing an epigenetic regulation by miR-7 and miR-30.

AIM: In this paper, inspiring Darwin’s theory, we propose a model which connects evolutions of neural circuits with evolutions of cosmos. In this model, in the beginning, there are some closed strings which decay into two groups of open strings. METHODS: First group couple to our universe from one side and produce matters like some genes of DNAs and couple to an anti-universe from another side with opposite sign and create anti-matters like some anti-genes of anti-DNAs. Second group couple to the star and planet’s cores like the earth’s core from one side and produce anti-matters like stringy black anti-DNA and couple to outer layers of stars and planets like the earth from other side and produce matters like some genes of DNAs on the earth. Each DNA or anti-DNA contains some genetic circuits which act like the circuits of receiver or sender of radio waves. To transfer waves of these circuits, some neurons emerge which some of them are related to genetic circuits of anti-DNAs in anti-universe, and some are related to genetic circuits of stringy black anti-DNA within the earth’s core. A collection of these neural circuits forms the little brain on the heart at first and main brain after some time. RESULTS: To examine the model, we remove effects of matters in outer layers of earth in the conditions of microgravity and consider radiated signals of neural circuits in a chick embryo. We observe that in microgravity, more signals are emitted by neural circuits respect to normal conditions. This is a signature of exchanged waves between neural circuits and structures within the earth’s core. CONCLUSION: These communications help some animals to predict the time and place of an earthquake.

Following the US Food and Drug Administration (FDA) guidance on the evaluation of novel agents for the treatment of type 2 diabetes mellitus (T2DM), a number of cardiovascular outcomes safety trials (CVOTs) on sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been conducted. These trials show similarities in study design and definition of primary endpoints, but differ in their eligibility criteria. The aim of the present study was to investigate the generalizability of CVOTs on SGLT2i to Italian adults with T2DM; we estimated the proportions of this patient population who would be eligible for enrollment in EMPA-REG OUTCOME (empagliflozin), CANVAS (canagliflozin), DECLARE-TIMI 58 (dapagliflozin), and VERTIS-CV (ertugliflozin) studies. This observational, cross-sectional study was conducted in 222 Italian diabetes clinics. Data on 455,662 adult patients with T2DM seen during 2016 were analyzed against the published patient eligibility criteria for the four CVOTs. The current use of SGLT2i in potentially eligible patients was assessed. Among the population identified, the proportion of patients meeting major eligibility criteria was 11.7% for EMPA-REG OUTCOME, 29.4% for CANVAS, 55.9% for DECLARE-TIMI 58, and 12.8% for VERTIS-CV. Of the patients eligible for these CVOTs, only a minority (range 4.4–6.8%) was actually prescribed an SGLT2i. Compared with patients in the CVOTs, eligible patients in the real world showed older age and longer diabetes duration, lower BMI and HbA1c levels, lower prevalence of established cardiovascular and cerebrovascular disease, and higher rates of microvascular complications and peripheral arterial disease. The percentage of patients potentially eligible for treatment with SGLT2i varies as a reflection of different eligibility criteria applied in the trials. A large number of patients that could benefit from SGLT2i in terms of not only cardiovascular protection but also renal protection do not receive the treatment. AstraZeneca.

To recover chick embryos damaged the brain, two methods are presented. In both of them, somatic cells of an embryo introduced into an egg cell and an embryo have emerged. In one method, injured a part of the brain in the head of an embryo is replaced with a healthy part of the brain. In the second method, the heart of brain embryo dead is transplanted with the embryo heart. In this mechanism, new blood cells are emerged in the bone marrow and transmit information of transplantation to subventricular zone (SVZ) of the brain through the circulatory system. Then, SVZ produces new neural stem cells by a subsequent dividing into neurons. These neurons produce new neural circuits within the brain and recover the injured brain. To examine the model, two hearts of two embryos are connected, and their effects on neural circuits are observed.

Salmonella is a foodborne pathogen able to adhere and persist on biotic and abiotic surfaces, including vegetables, which are even more linked to foodborne outbreaks. In this work, first we investigated the capability of Salmonella to adhere on different surfaces (stainless steel, polypropylene and lettuce), then we evaluated the potential effect of essential oils in reducing the adhesion and persistence of the pathogen on lettuce. Eight essential oils (EO) were tested on five Salmonella enterica strains (serovars Derby, Thompson, Napoli, Kasenyi and Veneziana). Cinnamomum zeylanicum EO (CEO) was the most effective, according to Minimal Inhibitory Concentration (MIC 1.25–1.87 μL/mL) and to growth/inhibition dynamics. To simulate real conditions, a cocktail of Salmonella Kasenyi, S. Veneziana and S. Napoli was applied on the three surfaces, but it adhered only on lettuce, starting from 1 h of contact (4.59 ± 0.34 Log UFC/cm2). Five μL/mL CEO, applied on lettuce, immediately reduced the loosely and strongly attached cells (reduction of 0.78 Log and 0.63 Log CFU/cm2, respectively), with significant effect up to 120 h. CEO also inhibited the Polyphenol Oxidase activity, thus preserving lettuce colour during storage. Cinnamon EO could therefore help to improve safety and appearance of fresh-cut lettuce during storage.

Information on the common carotid artery and cerebral microcirculation can be obtained by micro-ultrasound (µUS). The aim of the study described here was to investigate high-fat diet-induced alterations in vascular parameters in ApoE–/– mice. Twenty-two ApoE–/– male mice were examined by µUS and divided into the standard diet (ApoE–/–SD) and high-fat diet (ApoE–/–HF) groups. The µUS examination was repeated after 4 mo (T1). Carotid stiffness, reflection magnitude and reflection index were measured; the amplitudes of the first (W1) and second (W2) local maxima, the local minimum (Wb) and the reflection index (RIWIA = Wb/W1) were assessed with wave intensity analysis. At T1, ApoE–/–HF mice had increased carotid stiffness (1.48 [0.36] vs. 1.88 [0.51]) and reflection magnitude (0.89 [0.07] vs. 0.94 [0.07]) values. Longitudinal comparisons highlighted increases in carotid stiffness for ApoE–/–HF mice (from 1.37 [0.25] to 1.88 [0.51] m/s) but not for ApoE–/–SD mice (from 1.40 [0.62] to 1.48 [0.36] m/s). ApoE–/–HF mice exhibited carotid artery stiffening and increased wave reflections.

Cancer is universally recognized as a heterogeneous disease. The different cell clones present in a tumor can display distinct molecular and phenotypic profiles, which may influence proliferation capabilities, metastatic potential and response to therapy. To better understand cancer progression and possibly design effective therapeutic strategies, it is fundamental to design cell-sorting technologies able to isolate rare, viable tumor cell clones from tissue or liquid biopsies. Fluorescence-activated cell sorting (FACS) is the most widely used technique to isolate cell populations from heterogeneous samples. However, FACS analysis presents technical limitations when applied to rare cell populations and/or samples with low cellularity and limitations associated with the low total number of target cells in the sample. DEParray™ PLUS (DA) is a highly automated image-based cell sorting technology capable of isolating pure, single and rare cells from heterogeneous samples. Here we evaluate the capabilities of the DA system to isolate a small number of viable tumor cells and assess the proliferation capacity of DA-sorted cells in comparison with FACS-sorted cells. Human Jurkat T lymphoblast cell line were cultured in RPMI medium and a double staining procedure was optimized to label cells with CellTraceFarRed (CTFR), division tracking dye and Live/Dead (LD) Fixable marker. CTFR/LD staining was performed for each experiment and, at days 0 and 7 of culture, CTFR and LD fluorescences were analyzed by means of BD CANTO II Flow cytometry. At day 0, FACS analysis discriminate dead from live cells, while at day 7 evaluate cell proliferation and viability after 7 days in culture. Comparison tests were carried out following two different recovery schemes: 1 recovery of 100 CTFR+/LD- cells pool and 10 recoveries of 10 CTFR+/LD- cells pool using DA Plus and BD FACSAria Fusion. For each experiment, the results were compared to cells seeded manually, which represent our unsorted control. When comparing the results obtained with a 100-cells pool, no significant difference in cell viability and proliferation were observed between DA-sorted and FACSAria-sorted cells after 7 days in culture. On the other hand, the 10 cells pool sorted with DA PLUS showed a significantly higher viability and proliferation rate compared to those sorted with FACSAria at day 7. Moreover, cells sorted by DA-technology showed less variation between experiments, highlighting a more robust performance when sorting a small number of cells. Overall, the results confirm the unique capability of the DA system to sort a small number of cells, which maintain a higher cell viability and proliferation capacity compared to those sorted with FACS. This opens up the possibility to isolate rare tumor cell clones for functional studies that can help to better understand tumor progression and response to therapy. Citation Format: Maximilian Sergio, Chiara Rossi, Valeria Stivani, Ilaria Maffei, Marco Rossi, Gianpiero Parisi, Gianni Medoro. Isolation of small number of tumor cells for proliferation studies using DEPArray technology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5324.

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by an excessive production of pro-inflammatory cytokines resulting in chronic inflammation and genomic instability. Besides the driver mutations in JAK2, MPL, and CALR genes, the deregulation of miRNA expression may also contribute to the pathogenesis of PMF. To this end, we recently reported the upregulation of miR-382-5p in PMF CD34+ cells. In order to unveil the mechanistic details of the role of miR-382-5p in pathogenesis of PMF, we performed gene expression profiling of CD34+ cells overexpressing miR-382-5p. Among the downregulated genes, we identified superoxide dismutase 2 (SOD2), which is a predicted target of miR-382-5p. Subsequently, we confirmed miR-382-5p/SOD2 interaction by luciferase assay and we showed that miR-382-5p overexpression in CD34+ cells causes the decrease in SOD2 activity leading to reactive oxygen species (ROS) accumulation and oxidative DNA damage. In addition, our data indicate that inhibition of miR-382-5p in PMF CD34+ cells restores SOD2 function, induces ROS disposal, and reduces DNA oxidation. Since the pro-inflammatory cytokine transforming growth factor-β1 (TGF-β1) is a key player in PMF pathogenesis, we further investigated the effect of TGF-β1 on ROS and miR-382-5p levels. Our data showed that TGF-β1 treatment enhances miR-382-5p expression and reduces SOD2 activity leading to ROS accumulation. Finally, inhibition of TGF-β1 signaling in PMF CD34+ cells by galunisertib significantly reduced miR-382-5p expression and ROS accumulation and restored SOD2 activity. As a whole, this study reports that TGF-β1/miR-382-5p/SOD2 axis deregulation in PMF cells is linked to ROS overproduction that may contribute to enhanced oxidative stress and inflammation. Our results suggest that galunisertib may represent an effective drug reducing abnormal oxidative stress induced by TGF-β1 in PMF patients. DATABASE LINKING: GEO: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE103464.

In the last years, due to new regulatory guidelines requiring a stringent documentation of cardiovascular (CV) safety of novel drugs for type 2 diabetes, cardiovascular outcomes safety trials (CVOTs) are requested. CVOTs increase the knowledge about the safety profile of the new drugs, but they have intrinsic limits that make difficult their transferability to clinical practice. For this reason, real world evidence is considered an important complement to experimental data. Among the glucagon-like peptide-1 receptor agonists, liraglutide in the LEADER CVOT demonstrated superiority in reducing the risk of major CV events (MACEs) vs. placebo. We conducted an observational, retrospective, longitudinal study based on 307 patients with T2DM treated with liraglutide under routine clinical practice conditions. Real world impact of liraglutide on metabolic control, CV risk factors, hypoglycemia and CV events was assessed. Improvements during 36 months were found in HbA1c (–1.0%; p Incidence of MACEs in this cohort was lower than in the LEADER study (2.59 vs. 3.4 events per 100 person-years), confirming CV safety of liraglutide even in the real world. On the other hand, a higher incidence of CV event in patients with established CV disease was documented (8.1 events per 100 person-years), in spite of the use of liraglutide. In conclusion, 36-month durability and CV safety of liraglutide were documented in a real world cohort of T2DM patients, with sustained benefits on a large array of CV risk factors.

Nucleocytosolic transport, a membrane process, is impaired in motor neurons in amyotrophic lateral sclerosis (ALS). This study analyzes the nuclear lipidome in motor neurons in ALS and examines molecular pathways linked to the major lipid alterations. Nuclei were obtained from the frozen anterior horn of the lumbar spinal cord of ALS patients and age-matched controls. Lipidomic profiles of this subcellular fraction were obtained using liquid chromatography and mass spectrometry. We validated the mechanisms behind presumable lipidomic changes by exploring ALS surrogate models including human motor neurons (derived from ALS lines and controls) subjected to oxidative stress, the hSOD-G93A transgenic mice, and samples from an independent cohort of ALS patients. Among the differential lipid species, we noted 41 potential identities, mostly belonging to phospholipids (particularly ether phospholipids, as plasmalogens), as well as diacylglycerols and triacylglycerides. Decreased expression of alkyldihydroxyacetonephosphate synthase (AGPS)-a critical peroxisomal enzyme in plasmalogen synthesis-is found in motor neuron disease models; this occurs in parallel with an increase in the expression of sterol carrier protein 2 (SCP2) mRNA in ALS and Scp2 levels in G93A transgenic mice. Further, we identified diminished expression of diacylglycerol-related enzymes, such as phospholipase C βI (PLCβI) and protein kinase CβII (PKCβII), linked to diacylglycerol metabolism. Finally, lipid droplets were recognized in the nuclei, supporting the identification of triacylglycerides as differential lipids. Our results point to the potentially pathogenic role of altered composition of nuclear membrane lipids and lipids in the nucleoplasm in the anterior horn of the spinal cord in ALS. Overall, these data support the usefulness of subcellular lipidomics applied to neurodegenerative diseases.

Background The European Society of Cardiology (ESC) recently defined cardiovascular risk classes for subjects with diabetes. Aim of this study was to explore the distribution of subjects with type 2 diabetes (T2D) by cardiovascular risk groups according to the ESC classification and to describe the quality indicators of care, with particular regard to cardiovascular risk factors. Methods The study is based on data extracted from electronic medical records of patients treated at the 258 Italian diabetes centers participating in the AMD Annals initiative. Patients with T2D were stratified by cardiovascular risk. General descriptive indicators, measures of intermediate outcomes, intensity/appropriateness of pharmacological treatment for diabetes and cardiovascular risk factors, presence of other complications and overall quality of care were evaluated. Results Overall, 473,740 subjects with type 2 diabetes (78.5% at very high cardiovascular risk, 20.9% at high risk and 0.6% at moderate risk) were evaluated. Among people with T2D at very high risk: 26.4% had retinopathy, 39.5% had albuminuria, 18.7% had a previous major cardiovascular event, 39.0% had organ damage, 89.1% had three or more risk factors. The use of DPP4-i markedly increased as cardiovascular risk increased. The prescription of secretagogues also increased and that of GLP1-RAs tended to increase. The use of SGLT2-i was still limited, and only slightly higher in subjects with very high cardiovascular risk. The overall quality of care, as summarized by the Q score, tended to be lower as the level of cardiovascular risk increased. Conclusions A large proportion of subjects with T2D is at high or very high risk. Glucose-lowering drug therapies seem not to be adequately used with respect to their potential advantages in terms of cardiovascular risk reduction. Several actions are necessary to improve the quality of care.

A way to control or cure viral diseases like the Coronavirus is the use of exchanged waves between viral RNAs and cellular DNAs. In this research, we propose a model to compare the structure of cells and Corona viruses with the structure of speakers/microphones and obtain the frequency and the shape of exchanged waves. This is a theoretical and a mathematical model. Real material of this model are both Coronaviruses and host cells. METHODS: In this model, the cellular DNA and viral RNA are formed from charged particles and by their motions, some electromagnetic waves are emerged. In fact, they act like the inductors within speakers/microphones and produce some magnetic fields. These fields interact with charges around nuclear and viral membranes and produce some currents along them. In these conditions, membranes act like the magnet within speakers/microphones and emit some new magnetic fields. These fields interact with DNA and viral inductors, move them and produce some extra magnetic waves, These waves move charges along viral and nuclear membranes, vibrate them and produce some sound waves. RESULTS : Shape of DNA ultrasound waves depend on their RNA/DNA sources. A cellular DNA coils several times around the histone and supercoiled axes and produce linear, toroid and round inductors. A viral RNA coils and creates round viral inductor. These inductors are formed from hexagonal and pentagonal bases and emit hexagonal/pentagound linear/curved sound waves. CONCLUSIONS: Frequency of DNA sound waves could be between 107-1020 (Hz). Also, frequency of viral sound waves could be between 107-1011 [KVirus/KCell] where KVirus, KCell are some constants depending on the genus of liquids within viral and cell membranes. In some conditions, KVirus/KCell=1 and virus could be absorbed by cells.

Several wearable devices for physiological and activity monitoring are found on the market, but most of them only allow spot measurements. However, the continuous detection of physiological parameters without any constriction in time or space would be useful in several fields such as healthcare, fitness, and work. This can be achieved with the application of textile technologies for sensorized garments, where the sensors are completely embedded in the fabric. The complete integration of sensors in the fabric leads to several manufacturing techniques that allow dealing with both the technological challenges entailed by the physiological parameters under investigation, and the basic requirements of a garment such as perspiration, washability, and comfort. This review is intended to provide a detailed description of the textile technologies in terms of materials and manufacturing processes employed in the production of sensorized fabrics. The focus is pointed at the technical challenges and the advanced solutions introduced with respect to conventional sensors for recording different physiological parameters, and some interesting textile implementations for the acquisition of biopotentials, respiratory parameters, temperature and sweat are proposed. In the last section, an overview of the main garments on the market is depicted, also exploring some relevant projects under development.

Exorista larvarum (L.) (Diptera: Tachinidae), a larval parasitoid of Lepidoptera, can be reared from egg to fecund adult on artificial media composed of crude components. The standard in vitro culture is performed in 24-well plastic rearing plates. Exorista larvarum eggs, removed from superparasitized larvae of Galleria mellonella (L.) (Lepidoptera: Pyralidae), are individually placed in the wells, each containing a cotton swab soaked in liquid medium. The plates are then sealed until parasitoid puparium formation. To avoid contamination by microorganisms, the artificial medium is routinely supplemented with 0.01% solution of gentamicin. Experiments were carried out to assess whether this broad-spectrum antibiotic may be replaced with hydrolate of Monarda fistulosa L. (Lamiaceae), which was selected due to its high in vitro activity against pathogenic microorganisms for humans and plants. The hydrolate was either supplemented to the artificial medium (0.5% wt/wt) (first experiment) or placed in an empty well (200µl) of the rearing plate, to be supplied as saturated air due to evaporation (second experiment). In both experiments, a standard medium with gentamicin and an antimicrobial-free medium were maintained as positive and negative controls, respectively. In the first experiment, in the hydrolate-supplemented medium fewer E. larvarum completed egg-to-adult development than in the standard medium, but significantly more parasitoids developed from egg to adult compared to the antimicrobial-free medium. No significant difference was found between the numbers of eggs laid by the females obtained from the standard medium vs. those from the hydrolate-supplemented medium. In the second experiment, the hydrolate-saturated air significantly decreased E. larvarum egg hatching, puparium formation, and female fecundity compared to the standard medium. In perspective, M. fistulosa hydrolate supplemented to the artificial media for E. larvarum may be considered as a promising candidate to replace the gentamicin solution, as suggested also by the microbiological analyses of the media, performed at various growth stages of the parasitoid in a separate trial. Conversely, the hydrolate-saturated air treatment was deemed unsuitable.

Pseudomonas species are considered among the most important food spoilers thanks to the versatility to utilize a wide range of carbon sources and to grow under different environments. In the present study, proteomic responses of the blue pigmenting strain Pseudomonas uorescens pf59, chosen as representative strain of P. uorescens to application of environmental conditions such as low temperature (10 oC vs 30 oC) and extended incubation time (120 h vs 24 h), were evaluated under different culture media (Tryptic Soy Broth/Agar and Potato Dextrose Broth/Agar). In addition, bacterial growth dynamics, blue pigment production and bio lm formation of P. uorescens pf59 were investigated. The relative amount of some proteins categories, such as those related to carbohydrate and energy meta- bolism, post-translational modi cations, and fatty acid biosynthesis, was modulated in response to different environmental conditions. In particular, temperature in uenced protein synthesis more than culture medium, modulating the abundance of several proteins. In addition, at 120 h of incubation, aldehyde dehydrogenase, peroxiredoxin, outer membrane protein W, and ATP-dependent chaperone ClpB were over-synthesized in both culture media. Production of blue pigment was found only after 120 h of incubation at 10 oC, using Potato Dextrose media. In this condition, we found a relationship between the blue colour appearance and the over- expression of four proteins involved in redox balance and osmotic-shock defence response. Our work contributes to the knowledge of proteome dynamics used by P. uorescens underlying the microbial responses to various environmental conditions. The results provide useful indications to improve the ef cacy of intervention methods to inhibit the survival of microorganisms in foods.