An RFID-Based Tracing and Tracking System for the Fresh Vegetables Supply Chain

The paper presents an innovative gapless traceability system able to improve the main business processes of the fresh vegetables supply chain. The performed analysis highlighted some critical aspects in the management of the whole supply chain, from the land to the table of the end consumer, and allowed us to reengineer the most important processes. In particular, the first steps of the supply chain, which include cultivation in greenhouses and manufacturing of packaged vegetables, were analyzed. The re-engineered model was designed by exploiting the potentialities derived from the combined use of innovative Radio Frequency technologies, such as RFID and NFC, and important international standards, such as EPCglobal. The proposed tracing and tracking system allows the end consumer to know the complete history of the purchased product. Furthermore, in order to evaluate the potential benefits of the reengineered processes in a real supply chain, a pilot project was implemented in an Italian food company, which produces ready-to-eat vegetables, known asIV gammaproducts. Finally, some important metrics have been chosen to carry out the analysis of the potential benefits derived from the use of the re-engineered model

Systematic causality assessment of adverse events following HPV vaccines: Analysis of current data from Apulia region (Italy)

Since 2013, World Health Organization (WHO) recommended that adverse events following immuniza- tion (AEFIs) should be evaluated by a standardized algorithm for causality assessment, however the use of WHO procedure is rarely adopted. In Italy, AEFIs (classified only by temporal criteria) are registered in the National Drug Authority (AIFA) database, but causality assessment is not mandatory. Every year AIFA publishes the AEFIs report, that doesn’t contain information about causal correlation between events and vaccines. From AIFA database, we selected AEFIs following human papillomavirus vaccination (HPV) reported in Apulia (about 4,000,000 inhabitants) during 2008–2016. For serious AEFIs, we applied WHO causality assessment criteria; for cases hospitalized, we repeated the assessment getting additional information from health documentation. In 2008–2016, 100 HPV AEFIs (reporting rate: 17.8 per 100,000 doses) were registered of which 19 were serious (rate: 3.4 per 100,000 doses) and 12 led to hospitaliza- tion. After causality assessment, for 9 AEFIs the classification was ‘‘consistent causal association to immunization”, for 3 indeterminate, for 5 ‘‘inconsistent causal association to immunization” and for 2 not-classifiable. Among hospitalized patients, 5 AEFIs were consistent, 5 inconsistent, 1 not-classifiable and 1 indeterminate; adding information from health documentation, the results were similar except for indeterminate and not classifiable AEFIs that turned into ‘‘not consistent”. Only half of severe AEFIs could be associated with vaccination and this suggests that AIFA report provides a incomplete picture of HPV vaccine safety, with a risk for readers to confound ‘‘post hoc” and ‘‘propter hoc” approach without considering the causality assessment results. In the view of the systematic use of WHO causality assess- ment algorithm in the AEFI surveillance, the efforts of Public Health must be focused on the improvement of the quality of the information provided to reduce conclusions inter-observer variability; the routine follow-up of reports, also to collect additional information, must be guaranteed

In-hospital and web-based intervention to counteract vaccine hesitancy in very preterm infants’ families: a NICU experience

Background Vaccine hesitancy is a global problem, carrying significant health risks for extremely vulnerable population as that of preterm infants. Social media are emerging as significant tools for public health promotion. Our aim was to evaluate both the coverage and the timeliness of routine immunizations in a cohort of preterm infants (< 33 weeks of gestational age) at 24 months of age whose families have been subjected to in-hospital and web-based interventions to counteract vaccine hesitancy. Methods For a period of 2 years parents of preterm infants were instructed during their follow up visits by a member of the NICU team to get correct informations about vaccines from a social network page. Vaccination rates of preterm infants were assessed at 24 months of chronological age with an electronic database and compared to both general population and historical cohort. Results Coverage and timeliness of vaccinations at 24 months of age of 170 preterm infants were analyzed in December 2019. Gestational age and birth weight median (IQR) were, respectively, 31.0 (5.0) weeks and 1475.0 (843.8) g. Coverage rates were similar to those of the regional population (p > 0.05), while timeliness of administration was significantly delayed compared to the recommended schedule (p < 0.001). Age of administration was not correlated with either body weight and gestational age at birth (Spearman rank, p > 0.05). DTaP-IPV-HBV-Hib 2nd and 3rd doses, MMR and Varicella vaccines coverage data were higher compared to historical cohort (p < 0.05). Conclusion Increasing vaccine confidence through web-based interventions could have a positive impact on vaccination acceptance of parents of preterm infants, although timeliness results still delayed. There is a strong need to develop different and effective vaccination strategies to protect this very vulnerable population

Non-Coding RNAs in the Brain-Heart Axis: The Case of Parkinson’s Disease

Parkinson’s disease (PD) is a complex and heterogeneous disorder involving multiple genetic and environmental influences. Although a wide range of PD risk factors and clinical markers for the symptomatic motor stage of the disease have been identified, there are still no reliable biomarkers available for the early pre-motor phase of PD and for predicting disease progression. High-throughput RNA-based biomarker profiling and modeling may provide a means to exploit the joint information content from a multitude of markers to derive diagnostic and prognostic signatures. In the field of PD biomarker research, currently, no clinically validated RNA-based biomarker models are available, but previous studies reported several significantly disease-associated changes in RNA abundances and activities in multiple human tissues and body fluids. Here, we review the current knowledge of the regulation and function of non-coding RNAs in PD, focusing on microRNAs, long non-coding RNAs, and circular RNAs. Since there is growing evidence for functional interactions between the heart and the brain, we discuss the benefits of studying the role of non-coding RNAs in organ interactions when deciphering the complex regulatory networks involved in PD progression. We finally review important concepts of harmonization and curation of high throughput datasets, and we discuss the potential of systems biomedicine to derive and evaluate RNA biomarker signatures from high-throughput expression data

SARS-CoV-2 Breakthrough Infections: Incidence and Risk Factors in a Large European Multicentric Cohort of Health Workers

The research aimed to investigate the incidence of SARS-CoV-2 breakthrough infections and their determinants in a large European cohort of more than 60,000 health workers

Non-coding RNAs as prognostic biomarkers of cardiac arrest

L'arrêt cardiaque extra-hospitalier (ACEH) est l'une des principales causes de décès, touchant environ 100 personnes sur 100 000 par an en Europe. Une réanimation a été tentée dans 50 à 60 % des cas, et en moyenne, 8 % des survivants sont sortis de l'hôpital. Un pronostic précis de l'évolution de ces patients permettrait de mieux adapter les soins de santé. Malgré les progrès réalisés, le pronostic post-ACEH reste encore trop peu fiable. De ce fait, la découverte de nouveaux biomarqueurs spécifiques pourrait améliorer les approches actuelles. Les ARN non-codants détectés dans le sang représentent un réservoir de nouveaux biomarqueurs. Parmi eux, certains microARN (miARN) ont déjà été associés au pronostic des patients après un ACEH.Sur cette base, une première étude a pour but de déterminer si des miARN circulants pourraient refléter l'étendue des lésions cérébrales post-ACEH. À cette fin, des miARN ont été identifiés par séquençage du plasma prélevé 48h post-ACEH chez 50 patients provenant de l'essai TTM (Targeted Temperature Management) et sélectionnés selon leur évolution neurologique favorable ou défavorable, 6 mois post-ACEH. Ces miARN ont été corrélés avec l'énolase spécifique des neurones (NSE), un marqueur de lésions cérébrales. Parmi ces miARN, les miR-9-3p, miR-124-3p et miR-129-5p, connus comme étant enrichis dans le cerveau, ont montré une corrélation positive significative avec la NSE. De plus, ces 3 miARN se sont avérés être des prédicteurs de l’évolution neurologique post-ACEH. Ces résultats suggèrent que les niveaux circulants de ces miARN peuvent refléter l'étendue des lésions cérébrales, renforçant ainsi leur potentiel pour aider au pronostic de l’évolution post-ACEH.Dans une deuxième étude, l'objectif était d'identifier des longs ARN non-codants (ARNlnc) et des ARN circulaires (ARNcirc) capables de prédire l'évolution des patients après un ACEH. À cette fin, les échantillons sanguins prélevés 48h post-ACEH chez 46 patients TTM sélectionnés en fonction de leur évolution neurologique à 6 mois ont été séquencés. Parmi les candidats identifiés, 5 ARNcirc (circAGO2, circDLG1, circDNM2, circFAM13b et circNFAT5) et 1 ARNlnc (lnc-IL1R1-1:2) ont été sélectionnés et mesurés par qPCR chez les 542 patients restants de l’étude TTM. La capacité de ces 6 candidats à prédire l’évolution neurologique a été évaluée par régression logistique, et la survie grâce aux courbes de Kaplan-Meier et aux modèles de Cox. Parmi les candidats étudiés, circNFAT5 fût le meilleur pour prédire l’évolution neurologique et la survie 6 mois post-ACEH. Par conséquent, cet ARNcirc fût sélectionné pour des études fonctionnelles in-vitro. Dans les modèles in-vitro imitant un syndrome post-arrêt cardiaque, circNFAT5 fût modulé lors de l'activation des cellules T et des monocytes, suggérant un lien possible entre cet ARNcirc et le processus inflammatoire post-ACEH. De plus, des expériences préliminaires ont suggéré une relation indépendante de l'expression de circNFAT5 de celle de son gène parental, renforçant un rôle fonctionnel indépendant de circNFAT5. Après avoir investigué plusieurs pistes, aucune d’entre elles n’a permis d’identifier formellement les fonctions de circNFAT5. Par conséquent, des explorations futures seront nécessaires pour comprendre les fonctions biologiques de circNFAT5. Enfin, les 3 ARNcirc les plus performants identifiés dans l'étude TTM ont également été mesurés par qPCR chez les 674 patients de l'essai TTM2. Les 3 ARNcirc ont confirmés leur capacité de prédiction de l’évolution neurologique et de la survie, mais uniquement dans le groupe de patients traités en normothermie. CircDNM2 fût le candidat le plus performant dans cette étude.En conclusion, ce projet visait à investiguer l'utilisation potentielle des ARNnc comme biomarqueurs après un ACEH et représente un point de départ pour de futures études sur l'utilité clinique et les mécanismes d'action des candidats identifiés pour le pronostic des patients après un ACEH.Cardiac arrest is one of the leading causes of death worldwide, affecting on average 100 out of 100,000 people per year in Europe. Of these, resuscitation is attempted in 50-60% of cases, and survivors to hospital discharge average 8%. Accurate prediction of the outcome of these patients would help adapt health care. However, despite progress in this field, the prognosis of these patients remains poor. Therefore, the discovery of new specific biomarkers could improve current multimodal prediction approaches. Non-coding RNAs (ncRNAs) detected in blood represent a reservoir of novel biomarkers. Among them, circulating levels of micro RNAs (miRNA) have already been shown to be associated with outcome prediction of patients after out-of-hospital cardiac arrest (OHCA).In light of this, an initial study was designed to determine whether the levels of miRNAs identified in patients after OHCA may indeed reflect the extent of brain damage. To this end, circulating levels of miRNAs were assessed by sequencing plasma samples collected 48h after ROSC of 50 patients from the Targeted Temperature Management (TTM) trial grouped according to their favourable or unfavourable neurological outcome, 6 months after OHCA. These miRNAs were correlated with neuron-specific enolase (NSE), a marker of brain damage. Among miRNAs, brain-enriched miR9-3p, miR124-3p and miR129-5p showed significant positive correlation with NSE. Furthermore, all 3 miRNAs showed to be predictors of neurological outcome. Thus, these results indicated that circulating levels of brain-enriched microRNAs may indeed reflect the extent of brain damage, strengthening their potential to aid in the outcome prognostication after OHCA.In a second study, the goal was to identify potential long ncRNAs (lncRNA) and circular RNAs (circRNA) able to predict the outcome of patients after OHCA. To this end, whole blood samples of 46 TTM patients grouped according to their neurological outcome were sequenced. Among the lncRNAs and circRNAs identified, 5 circRNAs (circAGO2, circDLG1, circDNM2, circFAM13b and circNFAT5) and 1 lncRNA (lnc-IL1R1-1:2) were selected and measured by qPCR in the remaining TTM samples (n=542). The ability of candidates to predict neurological outcome was assessed by logistic regression and survival with Kaplan-Meier and Cox proportional hazards curves. Among the selected candidates, circNFAT5 performed best in predicting neurological outcome and survival 6 months after OHCA. Therefore, this circRNA was selected for preliminary in-vitro functional studies. Among the in-vitro treatments mimicking a post-cardiac arrest syndrome, circNFAT5 was found to be significantly modulated upon activation of T-cells and monocytes, suggesting an association of this circRNA with the inflammatory process occurring after OHCA. Furthermore, preliminary experiments suggested an independent relationship of circNFAT5 expression with its parental gene, strengthening the belief of a functional regulatory role of circNFAT5. Although, different attempts were made to elucidate the regulatory mechanisms of action of circNFAT5, no potential functions could be delineated in this work. Therefore, future explorations are needed to shed light on the possible biological functions performed by circNFAT5. Finally, the 3 best performing circRNAs identified in the TTM-trial were also measured by qPCR in 674 patients of the TTM2-trial. Following the same analyses presented in TTM, the three circRNAs were confirmed as independent predictors of neurological outcome and survival, but only in the normothermia group of TTM2, with circDNM2 as best performing candidate.In conclusion, this project aimed to deepen the understanding of the potential use of ncRNAs as biomarkers after OHCA and represented a starting point for future studies focusing on the clinical utility and mechanisms of action of the identified candidates in the outcome prognostication of patients after OHCA

Les ARNs non-codants comme biomarqueurs pronostiques de l’arrêt cardiaque

Cardiac arrest is one of the leading causes of death worldwide, affecting on average 100 out of 100,000 people per year in Europe. Of these, resuscitation is attempted in 50-60% of cases, and survivors to hospital discharge average 8%. Accurate prediction of the outcome of these patients would help adapt health care. However, despite progress in this field, the prognosis of these patients remains poor. Therefore, the discovery of new specific biomarkers could improve current multimodal prediction approaches. Non-coding RNAs (ncRNAs) detected in blood represent a reservoir of novel biomarkers. Among them, circulating levels of micro RNAs (miRNA) have already been shown to be associated with outcome prediction of patients after out-of-hospital cardiac arrest (OHCA).In light of this, an initial study was designed to determine whether the levels of miRNAs identified in patients after OHCA may indeed reflect the extent of brain damage. To this end, circulating levels of miRNAs were assessed by sequencing plasma samples collected 48h after ROSC of 50 patients from the Targeted Temperature Management (TTM) trial grouped according to their favourable or unfavourable neurological outcome, 6 months after OHCA. These miRNAs were correlated with neuron-specific enolase (NSE), a marker of brain damage. Among miRNAs, brain-enriched miR9-3p, miR124-3p and miR129-5p showed significant positive correlation with NSE. Furthermore, all 3 miRNAs showed to be predictors of neurological outcome. Thus, these results indicated that circulating levels of brain-enriched microRNAs may indeed reflect the extent of brain damage, strengthening their potential to aid in the outcome prognostication after OHCA.In a second study, the goal was to identify potential long ncRNAs (lncRNA) and circular RNAs (circRNA) able to predict the outcome of patients after OHCA. To this end, whole blood samples of 46 TTM patients grouped according to their neurological outcome were sequenced. Among the lncRNAs and circRNAs identified, 5 circRNAs (circAGO2, circDLG1, circDNM2, circFAM13b and circNFAT5) and 1 lncRNA (lnc-IL1R1-1:2) were selected and measured by qPCR in the remaining TTM samples (n=542). The ability of candidates to predict neurological outcome was assessed by logistic regression and survival with Kaplan-Meier and Cox proportional hazards curves. Among the selected candidates, circNFAT5 performed best in predicting neurological outcome and survival 6 months after OHCA. Therefore, this circRNA was selected for preliminary in-vitro functional studies. Among the in-vitro treatments mimicking a post-cardiac arrest syndrome, circNFAT5 was found to be significantly modulated upon activation of T-cells and monocytes, suggesting an association of this circRNA with the inflammatory process occurring after OHCA. Furthermore, preliminary experiments suggested an independent relationship of circNFAT5 expression with its parental gene, strengthening the belief of a functional regulatory role of circNFAT5. Although, different attempts were made to elucidate the regulatory mechanisms of action of circNFAT5, no potential functions could be delineated in this work. Therefore, future explorations are needed to shed light on the possible biological functions performed by circNFAT5. Finally, the 3 best performing circRNAs identified in the TTM-trial were also measured by qPCR in 674 patients of the TTM2-trial. Following the same analyses presented in TTM, the three circRNAs were confirmed as independent predictors of neurological outcome and survival, but only in the normothermia group of TTM2, with circDNM2 as best performing candidate.In conclusion, this project aimed to deepen the understanding of the potential use of ncRNAs as biomarkers after OHCA and represented a starting point for future studies focusing on the clinical utility and mechanisms of action of the identified candidates in the outcome prognostication of patients after OHCA.L'arrêt cardiaque extra-hospitalier (ACEH) est l'une des principales causes de décès, touchant environ 100 personnes sur 100 000 par an en Europe. Une réanimation a été tentée dans 50 à 60 % des cas, et en moyenne, 8 % des survivants sont sortis de l'hôpital. Un pronostic précis de l'évolution de ces patients permettrait de mieux adapter les soins de santé. Malgré les progrès réalisés, le pronostic post-ACEH reste encore trop peu fiable. De ce fait, la découverte de nouveaux biomarqueurs spécifiques pourrait améliorer les approches actuelles. Les ARN non-codants détectés dans le sang représentent un réservoir de nouveaux biomarqueurs. Parmi eux, certains microARN (miARN) ont déjà été associés au pronostic des patients après un ACEH.Sur cette base, une première étude a pour but de déterminer si des miARN circulants pourraient refléter l'étendue des lésions cérébrales post-ACEH. À cette fin, des miARN ont été identifiés par séquençage du plasma prélevé 48h post-ACEH chez 50 patients provenant de l'essai TTM (Targeted Temperature Management) et sélectionnés selon leur évolution neurologique favorable ou défavorable, 6 mois post-ACEH. Ces miARN ont été corrélés avec l'énolase spécifique des neurones (NSE), un marqueur de lésions cérébrales. Parmi ces miARN, les miR-9-3p, miR-124-3p et miR-129-5p, connus comme étant enrichis dans le cerveau, ont montré une corrélation positive significative avec la NSE. De plus, ces 3 miARN se sont avérés être des prédicteurs de l’évolution neurologique post-ACEH. Ces résultats suggèrent que les niveaux circulants de ces miARN peuvent refléter l'étendue des lésions cérébrales, renforçant ainsi leur potentiel pour aider au pronostic de l’évolution post-ACEH.Dans une deuxième étude, l'objectif était d'identifier des longs ARN non-codants (ARNlnc) et des ARN circulaires (ARNcirc) capables de prédire l'évolution des patients après un ACEH. À cette fin, les échantillons sanguins prélevés 48h post-ACEH chez 46 patients TTM sélectionnés en fonction de leur évolution neurologique à 6 mois ont été séquencés. Parmi les candidats identifiés, 5 ARNcirc (circAGO2, circDLG1, circDNM2, circFAM13b et circNFAT5) et 1 ARNlnc (lnc-IL1R1-1:2) ont été sélectionnés et mesurés par qPCR chez les 542 patients restants de l’étude TTM. La capacité de ces 6 candidats à prédire l’évolution neurologique a été évaluée par régression logistique, et la survie grâce aux courbes de Kaplan-Meier et aux modèles de Cox. Parmi les candidats étudiés, circNFAT5 fût le meilleur pour prédire l’évolution neurologique et la survie 6 mois post-ACEH. Par conséquent, cet ARNcirc fût sélectionné pour des études fonctionnelles in-vitro. Dans les modèles in-vitro imitant un syndrome post-arrêt cardiaque, circNFAT5 fût modulé lors de l'activation des cellules T et des monocytes, suggérant un lien possible entre cet ARNcirc et le processus inflammatoire post-ACEH. De plus, des expériences préliminaires ont suggéré une relation indépendante de l'expression de circNFAT5 de celle de son gène parental, renforçant un rôle fonctionnel indépendant de circNFAT5. Après avoir investigué plusieurs pistes, aucune d’entre elles n’a permis d’identifier formellement les fonctions de circNFAT5. Par conséquent, des explorations futures seront nécessaires pour comprendre les fonctions biologiques de circNFAT5. Enfin, les 3 ARNcirc les plus performants identifiés dans l'étude TTM ont également été mesurés par qPCR chez les 674 patients de l'essai TTM2. Les 3 ARNcirc ont confirmés leur capacité de prédiction de l’évolution neurologique et de la survie, mais uniquement dans le groupe de patients traités en normothermie. CircDNM2 fût le candidat le plus performant dans cette étude.En conclusion, ce projet visait à investiguer l'utilisation potentielle des ARNnc comme biomarqueurs après un ACEH et représente un point de départ pour de futures études sur l'utilité clinique et les mécanismes d'action des candidats identifiés pour le pronostic des patients après un ACEH

Non-Coding RNAs to Aid in Neurological Prognosis after Cardiac Arrest

Cardiovascular disease in general, and sudden cardiac death in particular, have an enormous socio-economic burden worldwide. Despite significant efforts to improve cardiopulmonary resuscitation, survival rates remain low. Moreover, patients who survive to hospital discharge have a high risk of developing severe physical or neurological symptoms. Being able to predict outcomes after resuscitation from cardiac arrest would make it possible to tailor healthcare approaches, thereby maximising efforts for those who would mostly benefit from aggressive therapy. However, the identification of patients at risk of poor recovery after cardiac arrest is still a challenging task which could be facilitated by novel biomarkers. Recent investigations have recognised the potential of non-coding RNAs to aid in outcome prediction after cardiac arrest. In this review, we summarize recent discoveries and propose a handful of novel perspectives for the use of non-coding RNAs to predict outcome after cardiac arrest, discussing their use for precision medicine

Approaching Sex Differences in Cardiovascular Non-Coding RNA Research

International audienceCardiovascular disease (CVD) is the biggest cause of sickness and mortality worldwide in both males and females. Clinical statistics demonstrate clear sex differences in risk, prevalence, mortality rates, and response to treatment for different entities of CVD. The reason for this remains poorly understood. Non-coding RNAs (ncRNAs) are emerging as key mediators and biomarkers of CVD. Similarly, current knowledge on differential regulation, expression, and pathology-associated function of ncRNAs between sexes is minimal. Here, we provide a state-of-the-art overview of what is known on sex differences in ncRNA research in CVD as well as discussing the contributing biological factors to this sex dimorphism including genetic and epigenetic factors and sex hormone regulation of transcription. We then focus on the experimental models of CVD and their use in translational ncRNA research in the cardiovascular field. In particular, we want to highlight the importance of considering sex of the cellular and pre-clinical models in clinical studies in ncRNA research and to carefully consider the appropriate experimental models most applicable to human patient populations. Moreover, we aim to identify sex-specific targets for treatment and diagnosis for the biggest socioeconomic health problem globally

Compliance with immunization and a biological risk assessment of heathcare workers as part of an occupational health surveillance program: the experience of a university hospital in southern Italy

Background: The active immunization of health care workers (HCWs) is a primary measure to prevent nosocomial infection; despite this, vaccine coverage among HCWs in most countries is low. To increase vaccine coverage in the health care setting, the hygiene and occupational medicine departments of Bari Policlinico General University-Hospital implemented a vaccination procedure. This operative procedure requires that during the occupational medical examination, all employees are evaluated for immunity/susceptibility to vaccine-preventable diseases, with vaccination offered to those determined to be susceptible. Methods: The study sample comprised HCWs who attended the biological risk assessment program from December 2017 to January 2019 (n = 449). Results: Susceptibility was higher for hepatitis B virus (23%), followed by rubella (11%), varicella (9%), mumps (8%), and measles (7%). The seroconversion rate after the administration of booster dose(s) was >80% for all vaccines. Overall, 15% of the HCWs refused the offered vaccine(s), and the main determinants of vaccination compliance were younger age (P < .0001) and being a physician (P < .05). Discussion: Despite the several recommendations and campaigns to promote vaccinations, achieving high immunization rates among HCWs is still a challenge. Conclusions: In this scenario, public health institutions have to choose between the enforcement of the promotion or the adoption of a mandatory policy