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Abstract Background and Objectives The aim of this analysis was to evaluate the long-term safety and effectiveness of lurasidone in the treatment of schizophrenia in adolescents and young adults (13–25). Methods The 2 pooled studies used similar designs and outcome measures. Patients (13–25) with schizophrenia completed an initial double-blind 6-week trial of lurasidone (40 and 80 mg/day) in the adolescent trial and (80 and 160 mg/day) in the young adult trial. In open-label long-term trials, adolescent patients were treated with 20–80 mg/day lurasidone, and adults were treated with 40–160 mg/day lurasidone. Efficacy was evaluated based on the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity Scale (CGI-S). Results The safety population consisted of 306 patients (mean age, 16.2 years; 208 patients (68.0%) who completed 12 months of treatment; 8.2% who discontinued treatment by 12 months due to an adverse event). The mean (SD) changes in the PANSS total score from the extension baseline to months 6 and 12 were − 11.8 (13.9) and – 15.3 (15.0), respectively (OC), and the mean (SD) changes in the CGI-S score were − 0.8 (1.0) and − 1.0 (1.1), respectively (OC). The most frequent adverse events were headache (17.6%), anxiety (11.4%), schizophrenia (9.8%), and nausea (9.8%). No clinically meaningful changes were observed in weight, metabolic parameters, or prolactin. Conclusions In adolescents and young adults with schizophrenia, treatment with lurasidone was generally well tolerated and effective. Long-term treatment was associated with a continued reduction in symptoms of schizophrenia. Long-term treatment was associated with minimal effects on weight, metabolic parameters, and prolactin. Clinicaltrials.gov identifiers D1050234, D1050302.

Abstract Background In humans, vestibular epilepsy (VE) is described as focal seizures with transient signs of vestibular disease. In dogs, 2 cases of vestibular episodes, called vestibular paroxysmia, are reported. Hypothesis/objectives The objective of this study was to define the clinical features, phenotypical manifestation, and outcome of suspected VE in dogs. Animals Ten dogs with recurrent vestibular episodes. Methods Retrospective study. Medical records between 2009 and 2023 were reviewed, and dogs with a normal neurological examination, a history of transient signs of vestibular disease, absence of abnormalities detected on blood exams and brain magnetic resonance imaging (MRI) or computed tomography (CT), besides a minimum 10‐month follow‐up were included. Clinical improvement was defined as a ≥50% reduction in frequency or the cessation of clinical signs after the onset of antiseizure medications (ASMs). Results Pugs were the most prevalent breed (5/10; 50%). In 2 cases, additional generalized tonic‐clonic (GTC) seizures were reported. MRI exam was performed in most cases (9/10; 90%), whereas 1 dog underwent a CT scan (1/10; 10%). Electroencephalography (EEG) was carried out in 3 dogs that showed interictal spikes in the fronto‐temporal and fronto‐parietal areas. All cases received ASMs, with clinical improvement in 10/10 dogs (100%). Conclusion and clinical importance The presence of GTC seizures, EEG interictal spikes, and responsiveness to ASMs supported the hypothesis of an epileptic origin of vestibular episodes and thus the existence of VE in these dogs, with a presumed idiopathic cause and apparent favorable outcome.

Background: Infections due to antibiotic resistant bacteria are increasing worldwide and while, the epidemiology of these pathogens is well described in adults, pediatric specific data are lacking. We sought to gain an understanding of the risk factors for multi-drug resistant Gram-negative (MDRGN) infections in our pediatric population. Methods: We performed a retrospective review of pediatric patients seen at a pediatric hospital system in 2022 who had a culture-positive MDRGN, which was defined as a gram-negative bacteria resistant or intermediate to at least 1 antibiotic in ≥ 3 antibiotic groups. Repeat positive cultures for the same MDRGN were considered a single infection episode if occurring within a 14-day period. Demographic, clinical, and microbiologic data was obtained from the electronic medical record. Fisher’s exact was used for analysis. Results: One hundred and seventy-nine children had 237 infection episodes during the study period. Eighty-one patients (45%) were male and the median age was 5.3 years. The most prevalent MDRGNs included: Escherichia coli (154, 65%), Klebsiella spp (52, 22%), and Enterobacter spp (16, 7%). Escherichia coli was significantly more likely than other pathogens to be isolated from the urine (P = 0.008). Compared to multi-drug resistant E. coli, patients with a non-E. coli MDRGN were significantly more likely to have an underlying medical condition, recent hospitalization and antibiotic use (P≤0.001 for each, Table 1). A carbapenem was administered in 32% (75/237) of infection episodes. There were only 6 carbapenem resistant organisms. Conclusions: In our study, E. coli was the most frequent MDRGN. Most patients with a non-E. coli MDRGN infection episode had an underlying medical condition, recent hospitalization and antibiotic use. Carbapenem resistance was infrequent, though surveillance studies are needed to identify changing antibiotic resistance patterns and to direct prevention measures.

Drawing on transformative experience theory (Pugh, 2011) and in collaboration with high school science teachers, the authors developed an intervention (Seeing Science project) leveraging everyday mobile technology as a tool for integrating in-school and out-of-school experience. Students were instructed to take pictures when they noticed connections to unit content and post these with a caption on a class site. The current study used design-based research methods to revise and evaluate the Seeing Science project over a 2-year period. Revisions to the project were informed by year one data and principles of the Teaching for Transformative Experiences in Science (TTES) instructional model. Data sources included project artifacts, student interviews, and teacher interviews. Revisions to the project resulted in higher quality posts in pre-AP biology classes and greater participation in regular biology classes. Furthermore, an analysis of posts, classroom observations, and student interviews revealed that the project helped some students connect in-school learning to out-of-school experience and undergo transformative experiences. The current study contributes to transformative experience theory by identifying and developing strategies for fostering transformative experiences. These strategies further inform the TTES model and may support depth of learning and career identification.

Abstract Background Recently, genetic predisposition to injury has become a popular area of research and the association between a few single nucleotide polymorphisms (SNPs) and the susceptibility to develop musculoskeletal injuries has been shown. This pilot study aimed to investigate the combined effect of common gene polymorphisms previously associated with muscle injuries in Italian soccer players. Results A total of 64 Italian male top football players (age 23.1 ± 5.5 years; stature 180.2 ± 7.4 cm; weight 73.0 ± 7.9 kg) were genotyped for four gene polymorphisms [ACE I/D (rs4341), ACTN3 c.1729C > T (rs1815739), COL5A1 C > T (rs2722) and MCT1 c.1470A > T (rs1049434)]. Muscle injuries were gathered for 10 years (2009–2019). Buccal swabs were used to obtain genomic DNA, and the PCR method was used to genotype the samples. The combined influence of the four polymorphisms studied was calculated using a total genotype score (TGS: from 0 to 100 arbitrary units; a.u.). A genotype score (GS) of 2 was assigned to the “protective” genotype for injuries, a GS of 1 was assigned to the heterozygous genotype while a GS of 0 was assigned to the “worst” genotype. The distribution of genotype frequencies in the ACE I/D (rs4341), ACTN3 c.1729C > T (rs1815739) and MCT1 c.1470A > T (rs1049434) polymorphisms was different between non-injured and injured football players (p = 0.001; p = 0.016 and p = 0.005, respectively). The incidence of muscle injuries was significantly different among the ACE I/D (rs4341), ACTN3 c.1729C > T (rs1815739) and COL5A1 C > T (rs2722) genotype groups, showing a lower incidence of injuries in the “protective” genotype than “worse” genotype (ACE, p

Objective: This study aimed to assess the relationship between dietary palmitic acid (PA) intake and its association with body fat deposition and metabolic flexibility (MF) in middle-aged healthy individuals. Methods: Fifteen healthy participants (n = 15; 6 males, 9 females) with a mean age of 54 were enlisted. They were subjected to graded exercise tests using a cycle ergometer coupled with a calorimeter. Respiratory gas exchange was evaluated to determine two MF parameters. First, the MF index was derived by multiplying peak fatty acid oxidation (PFO) per kg of fat-free mass (FFM) with the percentage of VO2max at PFO. The second parameter, peak energy substrates’ oxidation (aka PESO), was computed by aggregating the kilocalories from PFO and peak carbohydrate oxidation, normalized per kg FFM. Dietary intake was gauged using a 7-day dietary record. Spearman’s regression was employed to analyze the association between dietary intake of specific fat classes, PA, MF parameters, and body fat percentage. Results: Preliminary results demonstrate that dietary saturated fatty acids (SFA) within physiological limits correlate with enhanced substrate oxidation capacity. This suggests augmented MF in middle-aged subjects. Among dietary SFA, PA was identified as the primary factor in this favorable correlation. Conclusions: Our initial observations, even though preliminary, strongly suggest a beneficial association between PA intake, MF, and body fat percentage. This underscores the potential nutritional importance of PA in promoting MF. Significance Statement Disparities in data regarding the health effects of dietary fats may arise from the distinct roles various dietary fatty acids play in MF.

ABSTRACTWith the pandemic, there has been a global reduction in influenza virus circulation, with WHO reporting, during 2021/22 season, laboratory testing positivity rate for influenza of less than 3%. Influenza surveillance systems anticipated a peak of influenza cases in the Northern Hemisphere during 2022/2023 season and the Italian Ministry of Health recommended the routinary co-administration of influenza with bivalent COVID-19 vaccines for the 2022/2023 season. At the Vaccination Hub of the University Hospital (UH) of Palermo, more than 700 subjects received influenza and COVID-19 booster doses in co-administration, during the 2021/2022 season. A cross-sectional study analyzing attitudes and factors associated with adherence to influenza and COVID-19 seasonal vaccines co-administration was conducted at the Vaccination Hub of the UH of Palermo, from October to December 2022. Among the 1,263 respondents, 74.7% (n = 944) received the co-administration of seasonal influenza and COVID-19 vaccines. The main reason reported for accepting it was confidence in the recommendations of the Health Ministry (41.3%). At the multivariable analysis, subjects aged ≤ 59 y old (AdjOR: 2.48; CIs95%: 1.89–3.65), male (AdjOR: 1.51; CIs95%: 1.27–1.75), Health-care professionals (HCPs) (AdjOR: 1.66; CIs95%: 1.08–2.57) and those who received co-administration during 2021/2022 (AdjOR: 41.6; CIs95%: 25.5–67.9) were significantly more prone to receive co-administration during 2022/23 season. From data obtained, the role of HCPs in accepting and then promoting co-administration of COVID-19 and influenza vaccines is crucial, as well as receiving co-administration in the previous season that represented the main drive for accepting it in the following seasons, supporting safety and effectiveness of this procedure.

Background & Aims: Circulating HBV RNAs have been proposed as a biomarker that reflects the transcriptional activity of covalently closed circular DNA (cccDNA) and may help to evaluate HBV treatment activity. Different research assays have been proposed and, although two PCR-based research use only investigational assays have been developed, the lack of standardized protocols represents an important limitation. Here we have designed and generated a stable clonal cell line producing an RNA-based standard for the calibration of PCR-based circulating HBV RNA assays. Methods: HBV RNA-producing Huh7-derived stable cell lines were generated by transfecting pTriEX plasmids containing 1.1 unit length HBV DNA genomes carrying mutations in the catalytic site (YMAA mutation) and the TP domain (Y63F) of the polymerase, and the ε-loop of the pregenomic (pg)RNA (mutation A1G). Results: The clonal cell line (Huh7-3D29), carrying a double YMAA and Y63F mutation, displayed, and maintained over several passages in culture, a high RNA secretion phenotype with negligible residual secreted HBV DNA. Density gradient centrifugation showed that most of the secreted HBV RNA from Huh7-3D29 cells was detected in naked capsid and virion-like particles and only a minority in small extracellular vescicles. Nanopore sequencing of 5’RACE products shows that the majority of the Huh7-3D29-secreted HBV RNAs start at the 5' end of pgRNA and pgRNA-derived spliced RNAs. Finally, Huh7-3D29 cells showed a high and up-scalable secreted RNA yield allowing 1,300 standard curves in 9 days from one flask. Conclusion: We generated a clonal cell line that produces high quantities of HBV RNAs with very low quantities of contaminating HBV DNAs, representing a stable source of RNA standard for HBV RNA assay calibration. Impact and implications:: Several investigational assays and two research use only assays have been developed to detect and quantify circulating HBV RNAs, an emerging biomarker of covalently closed circular DNA transcriptional activity and target engagement by new HBV treatments. The lack of a unique molecular standard for circulating HBV RNA quantification represents an important limitation. Here we describe the generation of a stable clonal cell line producing and secreting an RNA-based standard containing all the HBV RNA species found in HBV patients’ sera (e.g. pgRNA, HBx transcripts). This new RNA standard can be used to calibrate all PCR-based assays for circulating HBV RNA quantification to evaluate, in a non-invasive manner, the size of the transcriptionally active cccDNA pool and the activity of novel strategies aimed at curing HBV infection.

Pedagogical metacognition, or the reflective and reflexive actions associated with teaching practice, strengthens the planning, monitoring, evaluation, and adjustment of teaching in higher education faculty. Learning communities are optimal environments to foster this active teaching reflection. This study incorporated pedagogical metacognition into a faculty learning community curriculum and explored its impacts on higher education instructors' reflective and reflexive practices. Faculty participants completed monthly metacognitive reflections for one academic year, each corresponding to a research-based principle of learning. Qualitative analysis indicated that faculty learning community participants recognized their lack of pedagogical training, successfully reflected on their teaching strategies, identified areas for improvement, and set goals to incorporate research-based strategies into their instruction. To maximize student learning, pedagogical metacognition should be included in higher education professional development to encourage reflection on and action upon one's teaching.

BackgroundHepatoblastoma (HB) is the most common pediatric hepatic malignancy. Despite the progress in HB treatment, investigating HB pathomechanisms to optimize stratification and therapies remains a focal point to improve the outcome for high-risk patients.MethodsHere, we pointed to explore the impact of these mechanisms in HB. An observational study was performed on liver samples from a cohort of 17 patients with a diagnosis of HB and two normal liver samples. The in vitro experiments were executed on the Huh6 human HB cell line treated with the FAK inhibitor TAE226.ResultsOur results highlight a significant up-regulation of mRNA and protein expression of FAK in livers from HB with respect to normal livers. The increased protein expression of total and Tyr397 phosphorylated FAK (pTyr397FAK) was significantly correlated with the expression of some epigenetic regulators of histone H3 methylation and acetylation. Of note, the expression of pTyr397FAK, N-methyltransferase enzyme (EZH2) and tri-methylation of the H3K27 residue correlated with tumor size and alpha-fetoprotein (AFP) levels. Finally, TAE226 caused a significant reduction of pTyr397FAK, epigenetic regulators, AFP, EPCAM, OCT4, and SOX2, in association with anti-proliferative and pro-apoptotic effects on HB cells.ConclusionOur results suggest a role of FAK in HB that requires further investigations mainly focused on the exploration of its effective diagnostic and therapeutic translatability.

White matter (WM) tract formation and axonal pathfinding are major processes in brain development allowing to establish precise connections between targeted structures. Disruptions in axon pathfinding and connectivity impairments will lead to neural circuitry abnormalities, often associated with various neurodevelopmental disorders (NDDs). Among several neuroimaging methodologies, Diffusion Tensor Imaging (DTI) is a magnetic resonance imaging (MRI) technique that has the advantage of visualizing in 3D the WM tractography of the whole brain non-invasively. DTI is particularly valuable in unpinning structural tract connectivity defects of neural networks in NDDs. In this study, we used 3D DTI to unveil brain-specific tract defects in two mouse models lacking the Nr2f1 gene, which mutations in patients have been proven to cause an emerging NDD, called Bosch-Boonstra-Schaaf Optic Atrophy (BBSOAS). We aimed to investigate the impact of the lack of cortical Nr2f1 function on WM morphometry and tract microstructure quantifications. We found in both mutant mice partial loss of fibers and severe misrouting of the two major cortical commissural tracts, the corpus callosum, and the anterior commissure, as well as the two major hippocampal efferent tracts, the post-commissural fornix, and the ventral hippocampal commissure. DTI tract malformations were supported by 2D histology, 3D fluorescent imaging, and behavioral analyses. We propose that these interhemispheric connectivity impairments are consistent in explaining some cognitive defects described in BBSOAS patients, particularly altered information processing between the two brain hemispheres. Finally, our results highlight 3DDTI as a relevant neuroimaging modality that can provide appropriate morphometric biomarkers for further diagnosis of BBSOAS patients.

Nursing homes (NHs) are crucial for de-hospitalization and addressing the needs of non-self-sufficient individuals with complex health issues. This study investigates the patient safety culture (PSC) in NHs within a northern Italian region, focusing on factor influencing overall safety perceptions and their contributions to subjective judgements of safety. A cross-sectional study was conducted on 25 NHs in the Autonomous Province of Trento. The Nursing Home Survey on Patient Safety Culture (NHSPSC) was utilized to assess PSC among NH staff. Multilevel linear regression and post hoc dominance analyses were conducted to investigate variabilities in PSC among staff and NHs and to assess the extent to which PSC dimensions explain overall perceptions of PS. Analysis of 1080 questionnaires (44% response rate) revealed heterogeneity in PSC across dimensions and NHs, with management support, organizational learning, and supervisor expectations significantly influencing overall safety perceptions. Despite some areas of concern, overall safety perceptions were satisfactory. However, the correlation between individual dimensions and overall ratings of safety was moderate, suggesting the need to enhance the maturity level of PSCs. Promoting a shift in PSC could enhance transparency, prioritize resident safety, empower nursing staff, and increase family satisfaction with care provided in NHs. The support provided by management to PSC appears essential to influence NH staff perceptions of PS.

BackgroundCOVID-19 vaccines have been approved due to their excellent safety and efficacy data and their use has also permitted to reduce neurological complications of SARS-CoV-2. However, clinical trials were underpowered to detect rare adverse events. Herein, the aim was to characterize the clinical spectrum and immunological features of central nervous system (CNS) immune-related events following SARS-CoV-2 vaccination.MethodsMulticenter, retrospective, cohort study (December 1, 2020-April 30, 2022). Inclusion criteria were (1) de novo CNS disorders developing after SARS-CoV-2 vaccination (probable causal relationship as per 2021 Butler criteria) (2); evidence for an immune-mediated etiology, as per (i) 2016 Graus criteria for autoimmune encephalitis (AE); (ii) 2015 Wingerchuk criteria for neuromyelitis optica spectrum disorders; (iii) criteria for myelitis.ResultsNineteen patients were included from 7 tertiary referral hospitals across Italy and France (one of them being a national referral center for AE), over almost 1 year and half of vaccination campaign. Vaccines administered were mRNA-based (63%) and adenovirus-vectored (37%). The median time between vaccination and symptoms onset was 14 days (range: 2-41 days). CSF was inflammatory in 74%; autoantibodies were detected in 5%. CSF cytokine analysis (n=3) revealed increased CXCL-10 (IP-10), suggesting robust T-cell activation. The patients had AE (58%), myelitis (21%), acute disseminated encephalomyelitis (ADEM) (16%), and brainstem encephalitis (5%). All patients but 2 received immunomodulatory treatment. At last follow-up (median 130 days; range: 32-540), only one patient (5%) had a mRS>2.ConclusionCNS adverse events of COVID-19 vaccination appear to be very rare even at reference centers and consist mostly of antibody-negative AE, myelitis, and ADEM developing approximately 2 weeks after vaccination. Most patients improve following immunomodulatory treatment.

Abstract Hepatitis B virus (HBV) may integrate into the genome of infected cells and contribute to hepatocarcinogenesis. However, the role of HBV integration in hepatocellular carcinoma (HCC) development remains unclear. In this study, we apply a high-throughput HBV integration sequencing approach that allows sensitive identification of HBV integration sites and enumeration of integration clones. We identify 3339 HBV integration sites in paired tumour and non-tumour tissue samples from 7 patients with HCC. We detect 2107 clonally expanded integrations (1817 in tumour and 290 in non-tumour tissues), and a significant enrichment of clonal HBV integrations in mitochondrial DNA (mtDNA) preferentially occurring in the oxidative phosphorylation genes (OXPHOS) and D-loop region. We also find that HBV RNA sequences are imported into the mitochondria of hepatoma cells with the involvement of polynucleotide phosphorylase (PNPASE), and that HBV RNA might have a role in the process of HBV integration into mtDNA. Our results suggest a potential mechanism by which HBV integration may contribute to HCC development.

The following paper sums up the history of Dr. Vincenzo Tiberio, a military physician from Italy, who lived around the second half of the past century. His life was dedicated to clinical research, particularly in the context of microorganism competition and mechanisms of transmission of infections. His scientific work, though significant and innovative, was adequately appreciated just many years after his death; a great loss for the scientific world since his discovery could have laid the groundwork for the development of antimicrobial drugs that can be used nowadays in the infection control strategies.

To build biophysically detailed models of brain cells, circuits, and regions, a data-driven approach is increasingly being adopted. This helps to obtain a simulated activity that reproduces the experimentally recorded neural dynamics as faithfully as possible, and to turn the model into a useful framework for making predictions based on the principles governing the nature of neural cells. In such a context, the access to existing neural models and data outstandingly facilitates the work of computational neuroscientists and fosters its novelty, as the scientific community grows wider and neural models progressively increase in type, size, and number. Nonetheless, even when accessibility is guaranteed, data and models are rarely reused since it is difficult to retrieve, extract and/or understand relevant information and scientists are often required to download and modify individual files, perform neural data analysis, optimize model parameters, and run simulations, on their own and with their own resources. While focusing on the construction of biophysically and morphologically accurate models of hippocampal cells, we have created an online resource, the Build section of the Hippocampus Hub -a scientific portal for research on the hippocampus- that gathers data and models from different online open repositories and allows their collection as the first step of a single cell model building workflow. Interoperability of tools and data is the key feature of the work we are presenting. Through a simple click-and-collect procedure, like filling the shopping cart of an online store, researchers can intuitively select the files of interest (i.e., electrophysiological recordings, neural morphology, and model components), and get started with the construction of a data-driven hippocampal neuron model. Such a workflow importantly includes a model optimization process, which leverages high performance computing resources transparently granted to the users, and a framework for running simulations of the optimized model, both available through the EBRAINS Hodgkin-Huxley Neuron Builder online tool.

Background: Several results support the hypothesis that a group of pathologies falling within the Neuromyelitis Optica Spectrum Disorders (NMOSD) diagnostic criteria may coexist with Connective Tissue Diseases (CTD) in patients with a high susceptibility to autoimmune conditions. However, the relationship between NMOSD and rheumatologic diseases deserves further investigations to clarify all clinical aspects of this coexistence. We designed a systematic review and a proportional meta-analysis to estimate the association between CTD and MNOSD, with the aim of helping to plan the best strategy to achieve the most significant public health benefit for these conditions. Methods: We conducted a systematic review of the literature published until February 2023, searching in four databases: PubMed, Web of Science, EmBase, and OVID. Then, we conducted a random-effects proportional meta-analysis and assessed the risk of bias of the included studies using the Joanna Briggs Institute checklist. Results: The literature search yielded an overall result of 3176 publications (272 from PubMed, 880 from Web of Science, 634 from EmBase and 1390 from OVID). Of these, 29 were included in this systematic review. Analyzing studies that recruited unselected patients with Systemic Lupus Erythematosus (SLE) and Sjogren Syndrome (SjS), the pooled percentages of NMOSD overlapping were 0.6% (95% Confidence Interval [95% CI]: 0.1%–1.4%,) and 6.5% (95% CI: 4.7–8.6), respectively. Studies enrolling rheumatologic patients with nervous system symptoms involvement reported higher percentage of NMOSD (i.e., among SjS patients, a pooled percentage of 26.5%, 95% CI: 5.5–54.6%, was found). Similarly, recruiting patients with NMOSD, we found pooled percentages of SjS or SLE respectively of 7.0% and 3.5%. Conclusions: Our research found that the coexistence of these two disorders was more frequent in female rheumatologic patients with a SjS diagnosis with neurological manifestations and in neurologic patients for whom a SjS diagnosis was suspected. Similarly, NMOSD are less frequently found in SLE and very rarely incident in Mixed Connective Tissue Disease (MCTD) patients. These considerations should be taken into account in clinical experience of rheumatologists and neurologists, since early diagnosis of both conditions may influence the timing of immunosuppressive therapy and the prevention of systemic disabilities.

We propose a novel method for assessing metabolic flexibility (MF) through indirect calorimetry. A total of twenty healthy volunteers (10 females; 10 males) aged 45–65 were categorized into a Low-Intensity activity group (LI, 0–1 session of 1 h per week) and a High-Intensity activity group (HI, 5–6 sessions of 2 h per week). Volunteers underwent a stepwise exercise test on a cycle ergometer, connected to a calorimeter, to examine respiratory gas exchange to evaluate peak fatty acid Oxidation (PFO) and peak carbohydrate oxidation (PCO). Circulating peroxisome proliferator-activated receptor α (PPARα) biomarkers, docosahexaenoic acid/eicosapentaenoic acid (DHA/EPA) ratio and N-oleoylethanolamine (OEA), and the endocannabinoid- 2-arachidonoylglycerol (2-AG), were evaluated. We developed two MF parameters: the MF index (MFI), calculated by the product of PFO normalized per kg of fat-free mass (FFM) and the percentage of VO2max at PFO, and the peak energy substrates’ oxidation (PESO), computed by summing the kilocalories from the PFO and PCO, normalized per kg FFM. The MFI and PESO were significantly different between the HI and LI groups, showing strong correlations with the circulating bioactive substances. Higher DHA/EPA ratio (p ≤ 0.05) and OEA (p ≤ 0.01), but lower 2-AG levels (p ≤ 0.01) were found in the HI group. These new parameters successfully established a functional link between MF and the balance of PPARα/endocannabinoid systems.

MicroRNAs are small ribonucleotides that act as key gene regulators. Their altered expression is often associated with the onset and progression of several human diseases, including cancer. Given their potential use as biomarkers, there is a need to find detection methods for microRNAs suitable for use in clinical setting. Field-effect-transistor-based biosensors (bioFETs) appear to be valid tools to detect microRNAs, since they may reliably quantitate the specific binding between the immobilized probe and free target in solution through an easily detectable electrical signal. We have investigated the detection of human microRNA 155 (miR-155) using an innovative capturing probe constituted by a synthetic peptide nucleic acid (PNA), which has the advantage to form a duplex even at ionic strengths approaching the physiological conditions. With the aim to develop an optimized BioFET setup, the interaction kinetics between miR-155 and the chosen PNA was preliminarily investigated by using surface plasmon resonance (SPR). By exploiting both these results and our custom-made bioFET system, we were able to attain a low-cost, real-time, label-free and highly specific detection of miR-155 in the nano-molar range.

Introduction & Background Globally, consumption of Fruit and Vegetables (F&V) remains below nutritional guidelines. Marketing healthy products can be complex for retailers, and a key challenge is the design of strategies that benefit retailers, e.g., through improved loyalty, and deliver progress on societal goals. Objectives & Approach This study evaluates a point-plus-cash frequency reward program where participants received points by purchasing selected F&V, redeemable against a reward (plush toys in the shape of F&V). We estimate the impact of the program using a difference-in-difference-in-difference model, which compares expenditures in several categories before, during, and after the promotional period, across two different years, and separately for consumers who redeemed a reward and those who did not. Identification includes weighting for the propensity scores, and using an instrumental variable approach. Relevance to Digital Footprints The data refers to grocery expenditure in five categories in the focal retailer for over 268,000 consumers, over 27 weeks for 2 years, as recorded through their loyalty card. Results The reward program significantly increased expenditures in F&V in the focal retailer during the promotional period. However, results differed depending on reward redemption. For reward-redeemers, the program increased expenditures in F&V as well as in other food categories, an effect that persisted – at a declining rate – after the program stopped. The program had a short-lived effect on non-rewards redeemers, who only increased F&V expenditures during the promotional period. Conclusions & Implications Results indicate that a loyalty program promoting sales of F&V can create win-win benefits to both society and the retailer: it increases expenditures on healthy foods (F&V), while improving overall loyalty (i.e., expenditures) to the retailer.