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Abstract Background As the global aging population expands, understanding older adults’ preferences for place of death becomes pivotal in ensuring person-centered end-of-life care. Objective This study aimed to investigate the influence of sociodemographic, health, and lifestyle-related factors on end-of-life care preferences of older adults in South Tyrol, Italy. Methods Employing a cross-sectional design, a population-based survey was conducted with a stratified probabilistic sample of adults aged ≥ 75 years in South Tyrol (Autonomous Province of Bolzano/Bozen, Italy). From a randomly selected sample of 3,600 older adults, participants were invited to respond to a questionnaire that included items on older adults’ preferences for place of death and socio-demographic and health- and lifestyle-related factors, including frailty (e.g., PRISMA-7). Descriptive and multinomial logistic regression analyses were performed. Results The majority (55.3%) of the 1,695 older adults (participation rate: 47%) expressed a preference for dying at home and 12.7% indicated a desire for specialized end-of-life care in a healthcare facility. However, 27.9% refrained from disclosing their end-of-life care preferences. The factors influencing these preferences concerning the place of death included age, native language, educational level, living situation, and community. Compared to the preference of dying at own home or home of family or friends, older adults aged ≥ 85 years (OR = 0.57, P = 0.002) and living in an urban area (OR = 0.40, P

Abstract Background Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma, with embryonal (ERMS) and alveolar (ARMS) representing the two most common histological subtypes. ARMS shows poor prognosis, being often metastatic at diagnosis. Thus, the discovery of novel biomarkers predictive of tumor aggressiveness represents one of the most important challenges to overcome and may help the development of tailored therapies. In the last years, miRNAs carried in extracellular vesicles (EVs), small vesicles of endocytic origin, have emerged as ideal candidate biomarkers due to their stability in plasma and their tissue specificity. Methods EVs miRNAs were isolated from plasma of 21 patients affected by RMS and 13 healthy childrens (HC). We performed a miRNA profile using the Serum/Plasma Focus microRNA PCR panels (Qiagen), and RT-qPCR for validation analysis. Statistically significant (p

Abstract Cerebrospinal fluid (CSF) core biomarkers of Alzheimer’s disease (AD), including amyloid peptide beta-42 (Aβ42), Aβ42/40 ratio, and phosphorylated tau (pTau), are precious tools for supporting AD diagnosis. However, their use in clinical practice is limited due to the invasiveness of CSF collection. Thus, there is intensive research to find alternative, noninvasive, and widely accessible biological matrices to measure AD core biomarkers. In this study, we measured AD core biomarkers in saliva and plasma by a fully automated platform. We enrolled all consecutive patients with cognitive decline. For each patient, we measured Aβ42, Aβ40, and pTau levels in CSF, saliva, and plasma by Lumipulse G1200 (Fujirebio). We included forty-two patients, of whom 27 had AD. Levels of all biomarkers significantly differed in the three biofluids, with saliva having the lowest and CSF the highest levels of Aβ42, Aβ40, and pTau. A positive correlation of pTau, Aβ42/40 ratio, and pTau/Aβ42 ratio levels in CSF and plasma was detected, while no correlation between any biomarker in CSF and saliva was found. Our findings suggest that plasma but not saliva could represent a surrogate biofluid for measuring core AD biomarkers. Specifically, plasma Aβ42/40 ratio, pTau/Aβ42 ratio, and pTau could serve as surrogates of the corresponding CSF biomarkers.

The Nooksack Dace (Rhinichthys cataractae sp. cataractae) is a federally endangered riffle specialist endemic to the lower Fraser Valley of British Columbia, Canada, with historic population declines associated with riffle loss from stream dredging, channelization, and excessive sediment inputs. To assess the effectiveness of riffle restoration as a recovery strategy, gravel and cobble riffles were constructed in two replicate tributaries of the Nooksack River as a before-after-control-impact experiment, measuring dace abundance, substrate composition, and invertebrate biomass before and one year after restoration. Nooksack Dace density increased significantly in cobble (but not gravel) treatments relative to control riffles. Dace abundance was strongly associated with increased availability of interstitial refuges rather than substrate effects on invertebrate prey abundance, suggesting that interstitial space limits adult dace abundance. Young-of-the-year dace were not observed in one of the two restored streams despite riffle restoration, indicating increased dace density due to aggregation in higher-quality restored riffles. This recruitment limitation indicates persistence of a population bottleneck at an early life history stage that is not addressed by successful restoration of adult riffle habitat.

Abstract Rhabdomyosarcomas (RMS) are pediatric mesenchymal-derived malignancies encompassing PAX3/7-FOXO1 Fusion Positive (FP)-RMS, and Fusion Negative (FN)-RMS with frequent RAS pathway mutations. RMS express the master myogenic transcription factor MYOD that, whilst essential for survival, cannot support differentiation. Here we discover SKP2, an oncogenic E3-ubiquitin ligase, as a critical pro-tumorigenic driver in FN-RMS. We show that SKP2 is overexpressed in RMS through the binding of MYOD to an intronic enhancer. SKP2 in FN-RMS promotes cell cycle progression and prevents differentiation by directly targeting p27Kip1 and p57Kip2, respectively. SKP2 depletion unlocks a partly MYOD-dependent myogenic transcriptional program and strongly affects stemness and tumorigenic features and prevents in vivo tumor growth. These effects are mirrored by the investigational NEDDylation inhibitor MLN4924. Results demonstrate a crucial crosstalk between transcriptional and post-translational mechanisms through the MYOD-SKP2 axis that contributes to tumorigenesis in FN-RMS. Finally, NEDDylation inhibition is identified as a potential therapeutic vulnerability in FN-RMS.

Type-2 diabetes affects an increasing percentage of the world’s population and its control through dietary management, involving the consumption of health-promoting foods or their derived supplements, is a common strategy. Several mushroom species have been demonstrated to be endowed with antidiabetic properties, resulting from their ability in improving insulin sensitivity and production, or inhibiting the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase. This study aimed to investigate for the first time the hypoglycemic properties of the edible mushroom Leccinum scabrum (Bull.) Gray. Mushroom extracts were prepared through the microwave-assisted extraction (MAE) technique using green solvents with different polarity degrees. The inhibition activity of all the obtained extracts on both α-glucosidase and α-amylase was evaluated and the highest activity was observed for the EtOAc extract which showed an IC50 value about 60-fold lower than the reference compound 1-deoxynojirimycin (DNJ) on α-glucosidase (0.42 ± 0.02 and 25.4 ± 0.6 µg/mL, respectively). As expected on the basis of the literature data concerning both α-glucosidase and α-amylase inhibition, a milder inhibition activity on pancreatic α-amylase was observed. Preliminary in vivo tests on Drosophila melanogaster carried out on the most active obtained extract (EtOAc) confirmed the in vitro observed hypoglycemic activity. Finally, the EtOAc extract metabolic profile was determined through GC-MS and HRMS analyses.

Breast milk is the natural source of nutrition for infants, but while it supports their health, it can also be a potential source of toxic inorganic particulate matter, and this applies to both breast milk and industrially produced milk. The aim of the present study was to evaluate the presence of nanoparticles in both breast milk and formula milk samples. We collected and analyzed, via a new electron scanning microscopic procedure, 19 samples of breast milk from Italian women and 19 formula milk samples produced by different companies. Organic–inorganic agglomerates were detected in 58% of formula and in 63% of breast milk samples, respectively. In addition, a significantly (p < 0.05) greater size of nanoparticles was observed in formula milk samples. The results, showing the presence of inorganic nanosized particles in breast and artificial milk, may lead to future studies aimed at investigating possible nanosized contamination of milk and identifying early prevention strategies for women and animals involved in the food chain.

Alzheimer’s disease (AD) is the most common neurodegenerative disorder and a leading cause of dementia. One major challenge for clinicians is accurately assessing the rate of disease progression (RoP) early in the diagnostic process, which is crucial for patient management and clinical trial stratification. This study evaluated the role of cerebrospinal fluid biomarkers—Aβ42, t-Tau, pTau, Neurogranin (Ng), and Neurofilament light-chain (NF-L)—in predicting RoP at the time of AD diagnosis. We included 56 AD patients and monitored cognitive impairment using MMSE scores at diagnosis and during six-month follow-up visits. RoP scores were calculated based on these assessments. Our correlation analyses revealed significant associations between RoP and pTau, Aβ42/Ng ratio, and NF-L levels. When patients were stratified by median RoP values into low-to-moderate (L-M: 2) groups, those in the U-M group had notably higher CSF NF-L levels compared to the L-M group. Logistic regression analysis further demonstrated that elevated CSF NF-L levels were predictive of a faster RoP. These findings highlight the potential of CSF NF-L as a prognostic biomarker for rapid disease progression in AD. By identifying patients at risk for accelerated cognitive decline, CSF NF-L could significantly enhance early intervention strategies and improve patient management in clinical settings.

Introduction: Horizontal violence (HV) is defined as “persistent exposure to interpersonal aggression and mistreatment from colleagues.” Our objective in this pilot, single-site study was to identify sources of HV toward emergency medicine (EM) residents, using the Negative Acts Questionnaire-Revised (NAQ-R). Methods: In this investigation we used a descriptive cross-sectional survey design to categorize HV. All voluntary participants were residents in an Accreditation Council for Graduate Medical Education- approved, three-year academic EM residency. Data were collected via electronic survey and occurred six months into an academic year. We collected demographic information and responses to the NAQ-R in 2020. Horizontal violence is subdivided into three categories: work-related; person-related; and physical intimidation. Emergency medicine residents answered questions as they related to their interactions with residents and support staff, which included nursing. Results: A total of 23 of 26 residents responded (89%). Participants were 56% women, 78% white, 11% Hispanic, and 89% heterosexual. Participant clinical year was 39% first-, 39% second-, and 22% third-year residents. Women reported a higher frequency of HV compared to men (1.3 vs 1.1, P =.01). By category, women indicated higher incidence of work-related violence from other residents (P = .05) and staff (P =.02). There was no difference in reported frequency of violence for interns compared to senior residents.  Conclusion: Our pilot study demonstrated horizontal violence toward EM residents exists and is more prevalent in women.

BackgroundDigital health technologies offer the potential to improve the daily lives of older adults, maintain their health efficiently, and allow aging in place. Despite increasing evidence of benefits and advantages, readiness for adopting digital interventions among older people remains underexplored. ObjectiveThis study aims to explore the relationships between sociodemographic-, health-, and lifestyle-related factors and technology use in everyday life and community-dwelling older adults’ readiness to adopt telemedicine, smartphones with texting apps, wearables, and robotics. MethodsThis was a cross-sectional, population-based survey study with a stratified probabilistic sample of adults aged 75 years or older living in South Tyrol (autonomous province of Bolzano/Bozen, Italy). A random sample of 3600 community-dwelling older adults living at home was invited to complete a questionnaire including single items (older adults’ readiness to use health technology) and scales (PRISMA-7; Program of Research on Integration of Services for the Maintenance of Autonomy). Descriptive and logistic regression analyses were performed to analyze the data. ResultsIn total, 1695 community-dwelling older adults completed the survey (for a response rate of 47%). In terms of potential digital health technology adoption, wearable devices were favored by 33.7% (n=571), telemedicine by 30.1% (n=510), smartphones and texting apps by 24.5% (n=416), and assistant robots by 13.7% (n=232). Sociodemographic-, health- and lifestyle-related factors, as well as the use of technology in everyday life, played a significant role in explaining readiness to adopt digital health technologies. For telemedicine, age ≥85 years (odds ratio [OR] 0.74, 95% CI 0.56-0.96), financial constraints (OR 0.68, 95% CI 0.49-0.95), and less than 2 hours of physical activity per week (OR 0.75, 95% CI 0.58-0.98) were associated with nonreadiness, while Italian-speaking participants (OR 1.54, 95% CI 1.16-2.05) and those regularly using computers (OR 1.74, 95% CI 1.16-2.60), smartphones (OR 1.69, 95% CI 1.22-2.35), and the internet (OR 2.26, 95% CI 1.47-3.49) reported readiness for adoption. ConclusionsCommunity-dwelling older adults display varied readiness toward the adoption of digital health technologies, influenced by age, mother tongue, living situation, financial resources, physical activity, and current use of technology. The findings underscore the need for tailored interventions and educational programs to boost digital health technology adoption among community-dwelling older adults.

Objectives Memorial Sloan Kettering Cancer Center (MSK) sought to empower patients and caregivers to be more proactive in requesting ethics consultations.Methods Functionality was developed on MSK’s electronic patient portal that allowed patients and/or caregivers to request ethics consultations. The Ethics Consultation Service (ECS) responded to all requests, which were documented and analysed.Results Of the 74 requests made through the portal, only one fell under the purview of the ECS. The others were primarily requests for assistance with coordinating clinical care, hospital resources or frustrations with the hospital or clinical team.Discussion To better empower patients and caregivers to engage Ethics, healthcare organisations and ECSs must first provide them with accessible, understandable and iterative educational resources.Conclusion After 19.5 months, the ‘Request Ethics Consultation’ functionality on the patient portal was suspended. Developing resources on the role of Ethics for our patients and caregivers remains a priority.

IntroductionCasirivimab and imdevimab (CAS/IMV) are two non-competing, high-affinity human IgG1 anti-SARS-CoV-2 monoclonal antibodies, that showed a survival benefit in seronegative hospitalized patients with COVID-19. This study aimed to estimate the day-28 risk of mechanical ventilation (MV) and death in individuals hospitalized for severe COVID-19 pneumonia and receiving CAS/IMV. Additionally, it aimed to identify variables measured at the time of hospital admission that could predict these outcomes and derive a prediction algorithm.MethodsThis is a retrospective, observational cohort study conducted in 12 hospitals in Italy. Adult patients who were consecutively hospitalized from November 2021 to February 2022 receiving CAS/IMV were included. A multivariable logistic regression model was used to identify predictors of MV or death by day 28 from treatment initiation, and β-coefficients from the model were used to develop a risk score that was derived by means of leave-one-out internal cross-validation (CV), external CV, and calibration. Secondary outcome was mortality.ResultsA total of 480 hospitalized patients in the training set and 157 patients in the test set were included. By day 28, 36 participants (8%) underwent MV and 28 died (6%) for a total of 58 participants (12%) experiencing the composite primary endpoint. In multivariable analysis, four factors [age, PaO2/FiO2 ratio, lactate dehydrogenase (LDH), and platelets] were independently associated with the risk of MV/death and were used to generate the proposed risk score. The accuracy of the score in the area under the curve (AUC) was 0.80 and 0.77 in internal validation and test for the composite endpoint and 0.87 and 0.86 for death, respectively. The model also appeared to be well calibrated with the raw data.ConclusionThe mortality risk reported in our study was lower than that previously reported. Although CAS/IMV is no longer used, our score might help in identifying which patients are not likely to benefit from monoclonal antibodies and may require alternative interventions.

Abstract Background Paediatric-type diffuse High-Grade Gliomas (PDHGG) are highly heterogeneous tumours which include distinct cell sub-populations co-existing within the same tumour mass. We have previously shown that primary patient-derived and optical barcoded single-cell-derived clones function as interconnected networks. Here, we investigated the role of exosomes as a route for inter-clonal communication mediating PDHGG migration and invasion. Results A comprehensive characterisation of seven optical barcoded single-cell-derived clones obtained from two patient-derived cell lines was performed. These analyses highlighted extensive intra-tumour heterogeneity in terms of genetic and transcriptional profiles between clones as well as marked phenotypic differences including distinctive motility patterns. Live single-cell tracking analysis of 3D migration and invasion assays showed that the single-cell-derived clones display a higher speed and longer travelled distance when in co-culture compared to mono-culture conditions. To determine the role of exosomes in PDHGG inter-clonal cross-talks, we isolated exosomes released by different clones and characterised them in terms of marker expression, size and concentration. We demonstrated that exosomes are actively internalized by the cells and that the inhibition of their biogenesis, using the phospholipase inhibitor GW4689, significantly reduced the cell motility in mono-culture and more prominently when the cells from the clones were in co-culture. Analysis of the exosomal miRNAs, performed with a miRNome PCR panel, identified clone-specific miRNAs and a set of miRNA target genes involved in the regulation of cell motility/invasion/migration. These genes were found differentially expressed in co-culture versus mono-culture conditions and their expression levels were significantly modulated upon inhibition of exosome biogenesis. Conclusions In conclusion, our study highlights for the first time a key role for exosomes in the inter-clonal communication in PDHGG and suggests that interfering with the exosome biogenesis pathway may be a valuable strategy to inhibit cell motility and dissemination for these specific diseases.

Abstract BMS‐986263 is a retinoid‐conjugated lipid nanoparticle delivering small interfering RNA designed to inhibit synthesis of HSP47 protein, a collagen‐specific chaperone protein involved in fibrosis development. This is a phase I, open‐label, two‐part study evaluating pharmacokinetics and safety of BMS‐986263 in participants with hepatic impairment (HI). Part 1 (n = 24) of this study enrolled two cohorts with mild and moderate HI and a separate cohort of age‐ and body mass index (BMI)‐matched participants with normal hepatic function. Part 2 enrolled eight participants with severe HI and eight age‐ and BMI‐matched participants with normal hepatic function. All participants received a single intravenous 90 mg BMS‐986263 infusion. Compared with normal‐matched participants, geometric mean area under the plasma concentration‐time curve time zero to the time of the last quantifiable concentration (AUC(0‐T)) and AUC from zero to infinity (AUC(INF)) of HSP47 siRNA were similar in participants with mild HI and 34% and 163% greater in those with moderate and severe HI, respectively, whereas the maximum plasma concentration was ~25% lower in mild and moderate HI groups but 58% higher in the severe HI group than in the normal group. Adverse events were reported by two of eight, four of eight, and three of eight participants with mild, moderate, or severe HI, respectively; none were reported in the normal‐matched group. Overall, single‐dose BMS‐986263 was generally safe and well‐tolerated and dose adjustment is not considered necessary for participants with mild or moderate HI. Although available data do not indicate that dose adjustment should be performed in patients with severe HI; the optimal posology of BMS‐986263 in patients with severe HI may be determined later in its clinical development when additional data to establish exposure‐safety/efficacy relationship becomes available.

Freshwater mussels (order: Unionida) are highly imperiled globally and are increasingly the focus of captive propagation efforts to protect and restore wild populations. The Upper Tennessee River Basin (UTRB) in Virginia is a freshwater biodiversity hotspot hosting at least 45 of North America’s ~300 species of freshwater mussels, including 21 threatened and endangered species listed under the U.S. Endangered Species Act. Recent studies have documented that viruses and other microbes have contributed to freshwater mussel population declines in the UTRB. We conducted a multi-year longitudinal study of captive-reared hatchery mussels released to restoration sites throughout the UTRB to evaluate their viromes and compare them to captive hatchery environments. We documented 681 viruses from 27 families. The hatchery mussels had significantly less viruses than those deployed to wild sites, with only 20 viruses unique to the hatchery mussels. After the hatchery mussels were released into the wild, their number of viruses initially spiked and then increased steadily over time, with 451 viruses in total unique to the mussels in the wild. We found Clinch densovirus 1 (CDNV-1), a virus previously associated with mass mortality events in the Clinch River, in all samples, but the wild site mussels consistently had significantly higher CDNV-1 levels than those held in the hatchery. Our data document substantial differences between the viruses in the mussels in the hatchery and wild environments and rapid virome shifts after the mussels are released to the wild sites. These findings indicate that mussel release programs might benefit from acclimatization periods or other measures to mitigate the potential negative effects of rapid exposure to infectious agents found in natural environments.

SARS-CoV-2 infections among vaccinated nursing home residents increased after the Omicron variant emerged. Data on booster dose effectiveness in this population are limited. During July 2021–March 2022, nursing home outbreaks in 11 US jurisdictions involving >3 infections within 14 days among residents who had received at least the primary COVID-19 vaccine(s) were monitored. Among 2,188 nursing homes, 1,247 outbreaks were reported in the periods of Delta (n = 356, 29%), mixed Delta/Omicron (n = 354, 28%), and Omicron (n = 536, 43%) predominance. During the Omicron-predominant period, the risk for infection within 14 days of an outbreak start was lower among boosted residents than among residents who had received the primary vaccine series alone (risk ratio [RR] 0.25, 95% CI 0.19–0.33). Once infected, boosted residents were at lower risk for all-cause hospitalization (RR 0.48, 95% CI 0.40–0.49) and death (RR 0.45, 95% CI 0.34–0.59) than primary vaccine–only residents.

Objective: The aim of this study is to investigate the difference in impact between distal transradial access (dTRA) and classical transradial access (TRA) on vascular function using flow-mediated vasodilation (FMD) following coronary diagnostic and therapeutic catheterizations.

IntroductionAnaphylaxis is among the most severe manifestations of allergic disorders, but its molecular basis remains largely unknown and reliable diagnostic markers are not currently available. MicroRNAs (miRNAs) regulate several pathophysiological processes and have been proposed as non-invasive biomarkers. Therefore, this study aims to evaluate their involvement in anaphylactic reaction and their value as biomarkers.MethodsAcute (anaphylaxis) and baseline (control) serum samples from 67 patients with anaphylaxis were studied. Among them, 35 were adults with drug-induced anaphylaxis, 13 adults with food-induced anaphylaxis and 19 children with food-induced anaphylaxis. The circulating serum miRNAs profile was characterized by next-generation sequencing (NGS). For this purpose, acute and baseline samples from 5 adults with drug-induced anaphylaxis were used. RNA was extracted, retrotranscribed, sequenced and the readings obtained were mapped to the human database miRBase_20. In addition, a system biology analysis (SBA) was performed with its target genes and revealed pathways related to anaphylactic mediators signaling. Moreover, functional and molecular endothelial permeability assays were conducted with miR-375-3p-transfected cells in response to cAMP.ResultsA total of 334 miRNAs were identified, of which 21 were significant differentially expressed between both phases. Extracellular vesicles (EVs) were characterized by Western blot, electron microscopy and NanoSight. A decrease of miR-375-3p levels was determined by qPCR in both serum and EVs of patients with anaphylaxis (****p

Rocky tide pools are transition environments whose communities are affected by sudden temperature, salinity and nutrient fluctuations. Furthermore, these environments are exposed to multiple stressors and can be easily altered by human trampling. In particular, specific studies on rock pool heterobranchs communities are lacking for the Mediterranean Sea. In this study, the community of Heterobranchia (Mollusca: Gastropoda) living in an anthropized rock pools system in western Adriatic (Ancona, Italy) has been investigated and a first checklist of the sea slugs in this urbanized areas is provided. During the four months survey, a total of 452 specimens, belonging to 19 species and 12 families was recorded. Notable findings were the first record of Placida dendritica for the Conero Riviera, and the first records of Doto cervicenigra and Ercolania viridis for the western Adriatic Sea. Identification of trophic categories showed a diversified assemblage in terms of food sources mirroring a surprising species diversity. Moreover, we provide here the description of a peculiar behavior possibly used by sea slugs to cope with the stressful conditions within this semi-closed system.

Purpose: Functional reserve represents the difference between an individual's ability to produce a maximum output function and the ability to perform a functional task. Several studies have documented an age-related decrease in functional reserve with oral tongue pressure generation. Whether this pattern is seen in pharyngeal swallowing pressures is unknown. The aim of this study was to investigate pharyngeal functional reserve using high-resolution manometry during normal-effort and effortful swallows. Method: Pharyngeal high-resolution manometry was performed on 38 younger healthy individuals (= 40 years) and 18 older healthy individuals (= 60 years) during normal-effort and effortful water swallows. Pressure metrics included maximum pressure in the velopharynx, tongue base, and hypopharynx, as well as pharyngeal contractile integral and minimum pressure in the upper esophageal sphincter (UES). Repeated-measures analysis of variance was used to determine the effects of swallow task, age, and pharyngeal region on pressure generation. Results: Maximum pharyngeal pressures and pharyngeal contractile integral were significantly increased during the effortful swallows compared to normal-effort swallows (p < 0.001), but there were no interactions between task and age in pharyngeal pressures. In the UES, minimum pressures were significantly elevated in older individuals during effortful swallows compared to normal-effort swallows (p = 0.007) but did not follow a pattern consistent with reduced functional reserve. Conclusions: Healthy individuals increase pharyngeal driving pressures during effortful swallows, without an age-related reduction in the magnitude of pressure increase. Thus, this study did not find evidence for an age-related reduction in pharyngeal functional reserve. The preserved ability to increase pharyngeal pressures during effortful swallowing in aging may support the use of behavioral swallowing interventions in older individuals without neuromuscular conditions.

Bioactive peptides (BPs) are a heterogeneous class of molecules found in a wide range of plant and animal sources. BPs have a number of different industrial applications including pharmacology (nutraceuticals), food, cosmetology, and pet food. Though BPs were initially used mainly as food additives, today the estimated peptide-based product market is around US $40 billion per year, highlighting consumer demand. The nutraceutical field is one of the most interesting applications for BPs, however there are some limitations to the efficacy of BPs in nutraceutical treatments, including low bioaccessibility and bioavailability. Thus, new extraction and isolation techniques have been developed, using both vegetable and animal sources, to obtain BPs with specific activities and improve the bioactivity and the bioavailability. Randomized clinical trials show a possible relationship between the administration of BPs and the reduction of several cardiovascular risk factors, including hypertension, hypercholesterolemia, hypertriglyceridemia and hyperglycaemia. In addition, BPs exhibit antioxidant, anti-inflammatory, antimicrobial, and anticancer potential, but long-term clinical studies are still needed. The aim of this review is to give a general introduction of BPs, describe their production and application methods, present data regarding bioactivity and bioavailability, and finally highlight the future prospects of this class of molecules in clinical practice.

Claudiu Ungureanu,1 Giuseppe Colletti,1 Marc Blaimont,1 Alexandre Avran2 1Department of Cardiology, Jolimont Hospital, La Louvière, Belgium; 2Department of Cardiology, Clinique Pasteur Essey les Nancy, Nancy, FranceCorrespondence: Claudiu Ungureanu, Department of Cardiology, Jolimont Hospital, Rue, Ferrer, 159, La Louvière, Belgium, Tel +32495489442, Email ungureanu.claudiu@ymail.comBackground: Percutaneous coronary intervention (PCI) of the “culprit” artery is the recommended mechanical reperfusion strategy in the setting of ST-segment elevation myocardial infarction (STEMI). As PCI of bypass grafts may be associated with higher risks and lower procedural success rates, in patients with a history of previous coronary artery surgery, PCI directed at revascularization of the native vessels should be considered, but this may be difficult in the setting of a chronically occluded artery.Case Presentation: A patient with a history of multivessel coronary artery disease and a chronic total occlusion (CTO) of the right coronary artery (RCA) requiring arterial bypass surgery, presented with an acute inferior STEMI and cardiogenic shock. It was felt that shock was caused by the acute thrombotic occlusion of a right internal thoracic artery (RITA) bypass graft that had been sequentially anastomosed to the left circumflex (LCx) and right coronary arteries. Despite initiation of extracorporeal membrane oxygenation (ECMO), the patient remained in refractory shock and acute revascularization of the right coronary artery was performed through the RITA bypass segment using antegrade access to the graft through the LCx and then a retrograde approach to open a CTO of the RCA. After successful revascularization, the patient was successfully weaned from ECMO. Over 12 months of follow-up, the patient did well and was documented to have improved left ventricular systolic function.Conclusion: This report is the first to document the successful use of a retrograde approach through an arterial graft segment to revascularize a chronic total occlusion in the setting of acute STEMI and cardiogenic shock.Keywords: chronic total occlusion, STEMI, rotational atherectomy, coronary bypass

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10–25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease.The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety.

Connecting physics with the humanities is a fascinating challenge and a complicated cultural task. Yet, it is exactly what the Italian secondary-school graduation exam requires in its oral part. Although it has been criticized by teachers and students, here I provide a list of real school life examples and discuss why this can be a great, innovative opportunity for physics teachers to highlight the cultural power and richness of the discipline they teach.

Arteriovenous Malformations are complex and challenging entities, and their treatment is often tailored on the patient. Interstitial sclerosing treatment with bleomycin is promising especially in cases where the aesthetical and/or functional burden of surgical intervention would be impactful as in the S3 AVM according to the SECg classification. We treated 15 patients presenting small (<10cm3) S3 arterio-venous malformations with 3 + 3 sessions of 15.000 IU of interstitial bleomycin. 9 patients presented moderate to good response to the first 3 sessions and thus surgical re-shaping was performed between the two cycles. US examination was done pre-treatment, before each session and every 3 months after the end of the protocol to assess the arterio-venous malformations. Fifteen of the seventeen patients concluded the protocol. 9 patients underwent surgical re-shaping while 6 skipped it because of their excellent response to the first 3 bleomycin injections. Major improvement in terms of appearance and symptoms (pulsations, ulcerations, bleeding or pain) were always achieved. There was a 20% of minor complications. The presented data are encouraging and seem to suggest that this may be a promising protocol to extend the use of bleomycin in arterio-venous malformations and reduce the impact of surgery. [ABSTRACT FROM AUTHOR]

Abstract Background Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease characterised by the loss of upper and lower motor neurons. Increasing evidence indicates that neuroinflammation mediated by microglia contributes to ALS pathogenesis. This microglial activation is evident in post-mortem brain tissues and neuroimaging data from patients with ALS. However, the role of microglia in the pathogenesis and progression of amyotrophic lateral sclerosis remains unclear, partly due to the lack of a model system that is able to faithfully recapitulate the clinical pathology of ALS. To address this shortcoming, we describe an approach that generates monocyte-derived microglia-like cells that are capable of expressing molecular markers, and functional characteristics similar to in vivo human brain microglia. Methods In this study, we have established monocyte-derived microglia-like cells from 30 sporadic patients with ALS, including 15 patients with slow disease progression, 6 with intermediate progression, and 9 with rapid progression, together with 20 non-affected healthy controls. Results We demonstrate that patient monocyte-derived microglia-like cells recapitulate canonical pathological features of ALS including non-phosphorylated and phosphorylated-TDP-43-positive inclusions. Moreover, ALS microglia-like cells showed significantly impaired phagocytosis, altered cytokine profiles, and abnormal morphologies consistent with a neuroinflammatory phenotype. Interestingly, all ALS microglia-like cells showed abnormal phagocytosis consistent with the progression of the disease. In-depth analysis of ALS microglia-like cells from the rapid disease progression cohort revealed significantly altered cell-specific variation in phagocytic function. In addition, DNA damage and NOD-leucine rich repeat and pyrin containing protein 3 (NLRP3) inflammasome activity were also elevated in ALS patient monocyte-derived microglia-like cells, indicating a potential new pathway involved in driving disease progression. Conclusions Taken together, our work demonstrates that the monocyte-derived microglia-like cell model recapitulates disease-specific hallmarks and characteristics that substantiate patient heterogeneity associated with disease subgroups. Thus, monocyte-derived microglia-like cells are highly applicable to monitor disease progression and can be applied as a functional readout in clinical trials for anti-neuroinflammatory agents, providing a basis for personalised treatment for patients with ALS.

Vascular malformations of the bone most often involve the cranio-facial area. Even in relevant peer reviewed journals, venous malformations are often misdiagnosed as “hemangiomas” or “angiomas” of the bone. By reviewing literature from the past 5 years (2013–2018), we found many reports of vascular malformations of the bone where the diagnosis was incorrect. Unfortunately, there is still much confusion in understanding and/or diagnosing vascular malformations, despite the fact that in recent years many papers tried to clarify this topic. The purpose of this article is to make a review of the scientific literature concerning vascular malformations of the bone which have been reported as angioma, hemangioma, or hemangioendothelioma, and have been published between January 2013 to October 2018. Clinical features, imaging and histologic reports contained in the papers were reviewed. Subsequently, after reviewing every single paper we reclassified the diagnosis according to the 2018 ISSVA classification. Almost all of the vascular anomalies presented in the reviewed papers as angiomas, hemangiomas, or hemangioendotheliomas were venous (mostly) or arteriovenous malformations. Therefore, only 8 out of 58 papers (14.7%) had an accurate diagnosis. Interestingly, all of the papers reporting cavernous or capillary hemangiomas were actually presenting venous malformations. Making a correct diagnosis is of primary importance because depending on the type of vascular anomaly, the treatment and the prognosis for the patient are very different. Everyone who approaches or describes a vascular anomaly of the bone should know and should adopt a correct and updated nosography.

Aim: To evaluate the performance of the multiple imputation (MI) method for estimating clinical effectiveness in pediatric Crohn’s disease in the ImproveCareNow registry; to address the analytical challenge of missing data. Materials & methods: Simulation studies were performed by creating missing datasets based on fully observed data from patients with moderate-to-severe Crohn’s disease treated with non-ustekinumab biologics. MI was used to impute sPCDAI remission statuses in each simulated dataset. Results: The true remission rate (75.1% [95% CI: 72.6%, 77.5%]) was underestimated without imputation (72.6% [71.8%, 73.3%]). With MI, the estimate was 74.8% (74.4%, 75.2%). Conclusion: MI reduced nonresponse bias and improved the validity, reliability, and efficiency of real-world registry data to estimate remission rate in pediatric patients with Crohn’s disease.