Burn patients still represent an important challenge in critical care medicine today. These patients can develop significant neurological conditions up to intracranial hypertension, but as they find themselves hospitalized outside of neurocritical care and are often subjected to sedation for the complex management, they are sometimes underestimated. The aim of this study is to evaluate the feasibility of non-invasive methods for the early diagnosis of intracranial hypertension in these patients. In this prospective observational study, adult burn patients admitted to intensive care within the first 8 hours of the event were enrolled. These patients were studied through ultrasound measurement of optic nerve sheath diameter and intracranial vessel velocimetry with transcranial Doppler. In the 20 patients studied, no frankly pathological values were identified in the 3 different measurement stages (within 8 hours of the burn, then at 48 and 96 hours) and no correlations were identified between the measured values and the extension of the burn with the related risk of mortality. However, this study, one of a kind, demonstrates that these non-invasive methods are applicable to this specific patient population, and can represent an effective method for reducing the incidence of complications that are dangerous for survival.

In Italy, the number of buildings that have fallen into disuse is huge; also the normative and regulative framework promoting public portfolio’s re-use and revitalisation is still unclear and blurred. Nevertheless, in the last ten years, these buildings have become fertile ground for innovation and creative experiences by civic actors. The rise of this new category of civic actors plays an important role, both from the institutional side and the kind of initiatives and practices they process. They act in different manners but according to an in-depth analysis they share similar patterns of behaviour. What has emerged is that, although the different contexts, where they operate, the institutional performances might be successful if only certain kinds of conditions are taken into consideration. Based on some basic features, civic actors and their dynamics with public administrations are analysed to understand conditions that allow revitalisation processes to be successful in unused public buildings.

We have studied the very large amount of literary works written by the Italian mystic Maria Valtorta to assess similarities and differences in her writings because she claims that most of them are due to mystical visions. We have used mathematical and statistical tools developed for specifically studying deep linguistic aspects of texts. The general trend indicates that the literary works explicitly attributable to Maria Valtorta differ significantly from her other literary works, that she claims are attributable to the alleged characters Jesus and Mary. Mathematically, they seem to have been written by different authors. The comparison with the Italian literature is very striking. A single author, namely Maria Valtorta, seems to be able to write texts so diverse to cover the entire mathematical range (suitable defined) of the Italian literature of seven centuries.

Pancreatic Ductal Adenocarcinoma (PDAC) is the most frequent infiltrating type of pancreatic cancer. The poor prognosis is due to the absence of specific biomarkers, aggressiveness and treatment resistance. PDAC is a deadly malignancy bearing distinct genetic alterations, the most common being those that cause cancer-causing versions of the KRAS gene. Cannabigerol (CBG) is a non-psychomimetic cannabinoid with anti-inflammatory property. Regarding CBG anticancer ef-fect, up to now there are only few evidence in human cancers. We investigated CBG effects on PDAC cell lines, PANC-1 and MIAPaCa-2. It was investigated CBG activity on cell viability, cell death and its effect of EGFR-RAS-associated signalling. Moreover, the potential synergistic effect of CBG in combination with gemcitabine (GEM) and paclitaxel (PTX) was investigated. MTT was applied to investigate CBG effect on PDAC cell lines viability. Annexin-V and Acridine Orange staining followed by cytofluorimetric analysis and Western blot were used to evaluate CBG effect on cell death. Modulation of EGFR-RAS-associated pathways was determined by Western Blot analysis and Milliplex multiplex assay. Moreover, by MTT data and Synergy finder software analysis the effect of the combination of CBG and chemotherapeutic drugs, was determined.

Radiotherapy commonly utilizes CBCT for patient positioning and treatment monitoring. CBCT is deemed to be secure for patients, making it suitable for the delivery of fractional doses. However, limitations such as a narrow field of view, beam hardening, scattered radiation artifacts, and variability in pixel intensity hinder the direct use of raw CBCT for dose recalculation during treatment. To address this issue, reliable correction techniques are necessary to remove artifacts and remap pixel intensity into HU values. This study proposes a deep-learning framework for calibrating CBCT images acquired with narrow FOV systems and demonstrates its potential use in proton treatment planning updates. Cycle-consistent GAN processes raw CBCT to reduce scatter and remap HU. Monte Carlo simulation is used to generate CBCT scans, enabling the possibility to focus solely on the algorithm’s ability to reduce artifacts and cupping effects without considering intra-patient longitudinal variability and producing a fair comparison between planning CT and calibrated CBCT dosimetry. To showcase the viability of the approach using real-world data, experiments were also conducted using real CBCT. Tests were performed on a publicly available dataset of 40 patients who received ablative radiation therapy for pancreatic cancer. The simulated CBCT calibration led to a difference in proton dosimetry of less than 2%, compared to the planning CT. The potential toxicity effect on the organs at risk decreased from about 50% (uncalibrated) up the 2% (calibrated). The gamma pass rate at 3%/2mm produced an improvement of about 37% in replicating the prescribed dose before and after calibration (53.78% vs 90.26%). Real data also confirmed this with slightly inferior performances for the same criteria (65.36% vs 87.20%). These results may confirm that generative artificial intelligence brings the use of narrow FOV CBCT scans incrementally closer to clinical translation in proton therapy planning updates.

Ever since pharmacy has become a profession, pharmacist's role has been continuously subjected to changes due to specific influences from historical, socio-economic, political, and scientific context. Nowadays the classic perception of pharmaceutical profession in Community Pharmacy is facing worldwide extinction due to many factors. Modern services, such as online, mail-order, and telephone-order pharmacies are increasingly gaining ground thanks to their ability to facilitate customer demand. However, at the same time, they are endangering “face-to-face” contact, affecting the building of customer loyalty based on direct “human” interaction, and consequently reducing pharmacists to mere commercial figures. Communication is in fact emphasized as the essential element to build a solid and appropriate interpersonal relationship with the client, to make the consultancy process effective, and to strengthen pharmacist's professionalism in community pharmacy. The aim of this work is to analyze pharmacist’s role in modern society by pinpointing the factors affecting pharmacy profession practice. Specific purpose will be improving both the academic training of future professionals and their capacity to approach public relations through a deepened study and practice of behavioral, communication, educational, and sociological methodologies and techniques that would allow the development of more effective communication skills useful for providing an efficient consultancy service.

Fourteen quinolizidine derivatives, structurally related to the alkaloids lupinine and cytisine and previously studied for other pharmacological aims, were presently tested for antiarrhythmic, inotropic, and chronotropic effects on isolated guinea pig heart tissues, and to assess calcium antagonism in comparison to amiodarone, lidocaine, procainamide, and quinidine. All compounds, but two, compared favorably with the reference drugs. Potent antiarrhythmic activity was observed for compounds (in increasing order) 4, 1, 6 and 5. The last compound N-(3,4,5-trimethoxybenzoyl)aminohomolupinane) was outstanding, exhibiting a nanomolar potency (EC50 = 0.017 µM) for the increase of threshold of ac-arrhythmia, and being devoid of antihypertensive activity against spontaneously hypertensive rats.

(1) Background: Ulcerative colitis (UC) is characterized by immune system dysregulation with frequent extraintestinal manifestations, including airways involvement. Reduction in CO diffusing capacity and functional alterations in small airways have been described. The extended analysis of Fractional Exhaled Nitric Oxide (FeNO), may distinguish the sites of production and the presence of small airways inflammation being a useful, non-invasive marker for these patient’s follow up. The aim of our study was to compare PFTs, FeNO and CANO values of UC patients with different clinical disease activity and healthy subjects to reveal lung function abnormalities and the presence of subclinical airway inflammation. (2) Methods: We enrolled 42 adult outpatients with different clinical activity stages of UC (mean age 39±13 years) and a healthy control group of 41 subjects (mean age 29±3 years). C-reactive protein (CRP) and FeNO values at different flows (50,100 and 200 ml/sec) were collected. All patients performed pulmonary function tests (PFT’s) with static volumes and diffusing capacity (DLCO). (3) Results: FENO, CANO and CRP values were significantly increased in UC patients when compared with controls (p=0.02 and p<0.0001, respectively) and proportionally to the disease activity (FeNO class 3: 27.1 ppb vs class 1-2: 6.2 ppb; CANO values class 3: 8.1 ppb vs class 1-2: 2.0 ppb (p < 0.0001). TLC and DLCO were significantly reduced in UC patients compared to controls (p=0.011 and p<0.0001, respectively). (4) The results of this study show significant lung functional abnormalities in UC patients and suggest the presence of airway inflammation directly correlated with the disease activity suggesting an integrated approach in routine assessment.

Optical properties of the cornea are responsible for correct vision, ultrastructure allows optical transparency and biomechanical properties governs the shape, elasticity or stiffness of the cor-nea affecting ocular integrity and intraocular pressure. Therefore, optical aberrations, corneal transparency, structure and biomechanics play a fundamental role in the optical quality of hu-man vision, ocular health and refractive surgery outcomes. However, the convergence of those properties is not yet reported at macroscopic scale within the hierarchical structure of the cornea. This work explores the relationships between biomechanics, structure and optical properties (corneal aberrations and optical density) at macrostructural level of the cornea through dual Placido-Scheimpflug imaging and air-puff tonometry systems in a healthy young adult popula-tion. Results showed convergence between optical transparency, corneal macrostructure and biomechanics.

The cornea is the optical window to the brain. Its optical and structural properties are responsible for optical transparency and vision. The shape, elasticity, rigidity or stiffness are given by its biomechanical properties, whose stability results in ocular integrity and intraocular pressure dynamics. Here, we report in vivo observation of structural changes and biomechanical alterations of the human cornea induced by acoustic wave pressure within the frequency range of 50-350 Hz and 90 dB of sound pressure level. Central corneal thickness (CCT) and eccentricity (e2) were measured using Scheimpflug imaging and biomechanical properties [corneal hysteresis (CH) and intraocular pressure (IOP] were assessed with air-puff tonometry in 6 young healthy subjects. At the specific 150 Hz acoustic frequency, the variation in CCT and e2 were of 0.058 and 7.33 µm, respectively. Biomechanical alterations were also observed in both IOP (decrease of 3.60 mmHg) and CH that showed an increase of 0.40 mmHg.

It is important to be able to detect and differentiate between distinct porcine enteric coronaviruses that can cause similar diseases. However, the existence of naturally occurring recombinant coronaviruses such as swine enteric coronavirus (SeCoV) can give misleading results with currently used diagnostic methods. Therefore, we have developed and validated three duplex real-time quantitative RT-PCR assays for the simultaneous detection of, and differentiation between, porcine epidemic diarrhea virus (PEDV) and SeCoV. Transmissible gastroenteritis virus (TGEV) is also detected by two out of these three assays. In addition, a novel triplex assay was set up that was able to detect and differentiate between these alphacoronaviruses and the porcine deltacoronavirus (PDCoV). The validated assays have low limits of detection, close to 100% efficiency and were able to correctly identify the presence of PEDV and SeCoV in 55 field samples, while 20 samples of other pathogens did not give a positive result. Implementing one or more of these multiplex assays into the routine diagnostic surveillance for PEDV will ensure that the presence of SeCoV, TGEV and PDCoV will not go unnoticed.

Taking advantage of tourists’ intensive flow, the SARS-CoV-2 virus rapidly spread causing thousands of deaths globally. Trying to contain the already pandemic virus, government travel restrictions were suddenly imposed. Consequently, the tourism industry, which at that moment employed one in ten workers globally, suddenly collapsed. Hundreds of thousands of workers immediately lost their income. Flights were cancelled, and thousands of tourists were stuck abroad with no means to return to their home countries. The gravity of the situation raised the question of whether there was scholarly knowledge that could have helped manage tourism during the current pandemic. To answer this question, a methodical literature review was performed, allowing for up to 900 publications to be analysed. Keywords used were pandemic, tourism, tourist and travel. Based on this process, 63 publications were selected for further analysis. Among these, less than 5% were focused on the tourism side of the problem. As such, this research concludes that, by the time the novel coronavirus emerged, there was, virtually, no scholarly knowledge on how to manage tourism during pandemic times so as to avoid chaos, and that the scholarly community studying related issues is very small. Moving forward, this article recommends that research funding agencies and universities encourage the sound development of this area of knowledge. Aspects that should be investigated include when, how and by whom should tourism be halted, as well as the feasibility of a Tourism World Fund for supporting related costs.

Since the first description of COVID-19 infection, among clinical manifestations of the disease including fever, dispnea, cough, fatigue, it was observed a high incidence of thromboembolic events potentially evolving towars ARDS and COVID-associated-coagulopathy (CAC).The hypercoagulation state is based on an interaction between thrombosis and inflammation. The so-called CAC represents a key aspect in the genesis of organ damage from SARS-CoV-2. The prothrombotic status in COVID-19 disease can be explained by the increase of coagulation levels of D-dimer, lymphocytes, fibrinogen, IL-6 and prothrombin time. Several mechanisms have been hypothesized to explain this hypercoagulable process such as inflammatory cytokine storm, platelet activation, endothelial dysfunction and stasis for a long time. The purpose of this narrative review is to provide an overview of the current knowledge on the pathogenic mechanisms of coagulopathy that may characterize COVID-19 infection and inform on new areas of research. New vascular therapeutic strategies are also reviewed.

Cigarette butts (CBs) are the most diffuse waste in the world, often abandoned in the environment without proper disposal. They are dangerous because of the numerous harmful chemicals poten-tially released in the environment. There are, in literature, several technological options for CB recycling, but some critical concerns could affect their effectiveness due to the quality and quantity of CB litter collected in the proper way. The present paper focuses on policy framework social behavior, waste collection and transport and technological processes. The Extended Producer Responsibility scheme for CBs is proposed at European level as an action to tackle CB litter and encourage sustainable product development. The CB waste collection and transport is a key step for bringing CB to the recycling process. The main concern is the small quantity of CBs collected: 0.06 % of the municipal waste and 0.18 % of the unsorted waste in the administrative area of Pe-rugia. Another crucial issue is the need for behavioral interventions to increase education and awareness of smoker citizens, addressing the discrepancy between smokers’ behaviors and beliefs.

Plant male sterility refers to the failure in the production of fertile pollen. It occurs spontaneously in natural populations and may be caused by genes encoded in the nuclear (genic male sterility; GMS) or mitochondrial (cytoplasmic male sterility; CMS) genomes. This feature has great agronomic value for the production of hybrid seeds and has been widely used in crops, such as corn, rice, wheat, citrus, and several species of the family Solanaceae. Mitochondrial genes determining CMS have been uncovered in a wide range of plant species. The modes of action of CMS have been classified in terms of the effect they produce in the cell, which ultimately leads to a failure in the production of pollen. Male fertility can be restored by nuclear-encoded genes, termed restorer-of-fertility (Rf) factors. CMS from wild plants has been transferred to species of agronomic interest through somatic hybridization. Somatic hybrids have also been produced to generate CMS de novo upon recombination of the mitochondrial genomes of two parental plants or by separating the CMS cytoplasm from the nuclear Rf alleles

Black-purple carrots possess, apart from carotenoids, high content of other bioactive pigments such as anthocyanins. However, both carotenoids and anthocyanins are modified over cold storage due to their lability. In this work, we investigated the effect of the postharvest elicitation on nutritional and organoleptic quality of purple carrots over storage at 5°C for 21 days. Based on our experience, we considered methyl jasmonate and abscisic acid as elicitors. The values obtained were compared with those provided by the fresh-untreated sample on the treatment day (ie, day 0) and after three-week storage (ie, on day 21), which were used as a reference. As a result, carotenoid content increased naturally in untreated samples over storage whereas anthocyanins maintained invariable. Also, physicochemical parameters reflected apparent organoleptic quality loss. However, the postharvest treatment of purple carrot samples with elicitors resulted in similar carotenoid content in elicited samples to fresh carrots on day 0 as well as lower concentration of anthocyanins and antioxidant activity. Besides, elicitation, particularly with abscisic acid, enabled purple carrot deterioration to be slowed down and, therefore, the organoleptic quality to be preserved. This suggests delaying effect of both elicitors on the spoilage rate of purple carrots over the storage time. These findings indicate that the postharvest application of elicitors may be an interesting conservation method, alternative to traditional procedures, to decelerate decomposition and extend shelf-life of purple carrots.

Keywords: standing water bodies, glacial lakes, freshwater biodiversity, eutrophication; nature conservation network

Corneal biomechanics is a hot topic in ophthalmology. The biomechanical properties of the cornea (BMPs) have important implications in the management and diagnosis of corneal diseases such as ectasia and keratoconus. In addition, the characterization of BMPs is crucial to model the predictability of a corneal surgery intervention, the outcomes of refractive surgery or follow-up of corneal diseases. The biomechanical behavior of the cornea is governed by viscoelastic properties that allow, among other structural implications, the damping of excess of intraocular pressure and reduce damage to the optic nerve. Currently, the most versatile and complete methods to measure corneal viscoelasticity are based on air-puff corneal applanation. However, those methods lack the ability to directly measure corneal viscosity. The aim of this work is to propose a new methodology based on the analysis of corneal air-puff measurements through the Standard Linear Solid model (SLSM) to provide analytical expressions to separately calculate the elastic and time-dependent (corneal retardation time and viscosity) properties. The results shown the mean values of elasticity (E), viscosity (Ƞ) and corneal retardation time (τ) in a sample of 200 young and healthy subjects. The influence of elasticity and viscosity on viscoelasticity, high-order corneal aberrations and optical transparency is investigated. Finally, the SLSM fed back from experimental E and Ƞ values was employed to compare the creep-relaxation response between normal, an ocular hypertension patient and Ortho-K user.

International literature data report that the increase of infectious risk may be due to heating, ventilation and air conditioning (HVAC) systems contaminated by airborne pathogens. Moreover, the presence of complex rotating dehumidification wheels (RDWs) may complicate the cleaning and disinfection procedures of the HVAC systems. We evaluated the efficacy of a disinfection strategy applied to the RDW of two hospitals HVAC systems. Hospitals have 4 RDW systems related to the surgical areas (SA1 and SA2) and to the intensive and sub-intensive cares (IC and sIC). Microbiological air and surfaces analysis were performed in HVAC systems, before and after the disinfection treatment. Hydrogen peroxide (12%) with silver ions (10 mg/L) was aerosolized in all the air sampling points, located close to the RDW device. After the air disinfection procedure, reductions of total microbial counts at 22°C and fungi were achieved in SA2 and IC HVAC systems. An Aspergillus fumigatus contamination (6 CFU/500L), detected in one air sample collected in the IC HVAC system, was eradicated after the disinfection. Surface samples proved a good microbiological quality. Results suggest the need of a disinfection procedure aimed to improve the microbiological quality of the complex HVAC systems, mostly in surgical and intensive care areas.

This study examined the tail dependency structure of sovereign credit risk and three global risk factors in BRICS countries using copulas approach, which is known for its ability to provide the “true” tail correlation based on the correct marginal distribution. The empirical results show that global market risk sentiment comoves with sovereign CDS spreads across BRICS countries under extreme market events, with Brazil having the highest co-dependency followed by China, Russia, and South Africa. Furthermore, oil price volatility is the second biggest risk factor correlated with sovereign CDS spreads for Brazil and South Africa while exchange rate risk exhibits very small co-dependence with sovereign CDS spreads under extreme market conditions dominated by tail events. On the contrary, exchange rate risk is the second largest risk factor co-moving with China and Russia’s sovereign CDS spreads while oil price volatility exhibits the lowest co-dependence to CDS in these countries. Between oil price and currency risk, evidence of single risk factor dominance is found for Russia where exchange rate risk is largely dominant. These results suggest that BRICS policymakers might consider financial sector regulations that mitigate risks spill-over such as targeted capital controls when markets are distressed.

Metal foams are widely studied as possible tools for the enhancement of heat transfer from hot bodies. The basic idea is that a metal foam tends to increase significantly the heat exchange area between the hot solid body and the external cooling fluid. For this reason, this class of porous materials are considered as good candidates for an alternative to finned surfaces, with different pros and cons. Among the pros, we mention the generally wider area of contact between solid and fluid. Among the cons is the difficulty of producing different specimens with the same inner structure, with the consequence that their performance may be significantly variable. This paper will offer a survey of the literature with a focus on the main heat transfer characteristics of the metal foams. Then, a numerical simulation of the heat transfer at the pore scale level for an artificial foam with a spatially periodic structure will be discussed. Finally, these numerical results will be employed to assess the macroscopic modelling of the flow and heat transfer in a metal foam.

Purpose To analyse diagnostic and therapeutic impact of molecular imaging TNM (miTNM) stage obtained with 18F-DCFPyL versus 18F-Fluorocholine in head to head comparison in biochemical recurrence (BCR) prostate cancer (PCa). Material and methods Patients with BCR PCa after radical treatment with previous 18F-Fluorocholine-PET/CT (negative or oligometastatic disease) were derived to 18F-DCFPyL-PET/CT. Patients were classified attending to: grade group, EAU classification, PSA, PSA doubling time (PSAdt) and PSA velocity (PSAvel). The overall detection rate (DR) and miTNM stage according to PROMISE criteria were assessed for both radiotracers and also correlation (Kappa). The influence of PSA and kinetics on both PET/CT (DR and miTNM) and predictive value of unfavourable kinetics on miTNM were determined. Cut-off PSA, PSAdt and PSAvel values able to predict PET/CT results were determined. Change in miTNM and treatment derived of 18F-DCFPyL information with respect to 18F-Fluorocholine was also evaluated. Results We studied 138 patients. 18F-DCFPyL showed a higher DR than 18F-Fluorocholine (64.5% vs 33.3%). 18F-DCFPyL and 18F-Fluorocholine detected T in 33.3% versus 19.6%, N in 27.5% versus 13.8%, M in 30.4% versus 8.7%. Both tracers DR showed significant associations with PSA and PSAvel. Significant association was only found between miTNM and PSA on 18F-Fluorocholine-PET/CT (p=0.033). For 18F-Fluorocholine and 18F-DCFPyL PET/CT a PSAdt cut-off of 4.09 and 5.59 months, respectively, were able to predict M stage. 18F-DCFPyL changed therapeutic management in 40/138 patients. Conclusion 18F-DCFPyL provides a higher DR and superior miTNM staging than 18F-Fluorocholine in restaging BCR, especially with high PSA and unfavourable PSA kinetics, showing a fair agreement to 18F-Fluorocholine.

Aging involves several changes depending on genetic and behavioural factors, such as lifestyle and number and quality of social relationships, which in turn can be influenced by empathy. Here, the change in the perceived social support across the life span as a function of empathy was investigated, considering the mediating role of the empathy, after controlling for gender and education. 441 people (18-91 years old) filled in the Italian short version of the Interpersonal Support Evaluation List (ISEL-12) and the Social Support Questionnaire (SSQ6) as well as the Empathy Questionnaire (EQ) and the Reading the Mind in the Eyes test (RMET). The mediation analyses with ISEL-12 showed that age and the EQ fully mediated the relationship between age and Appraisal, Belonging and Tangible scores. Further, the EQ fully mediated only the relationship between age and SSQ6-People. These results showed that empathic skills play a key role in the relationships between age and social support. This suggests: empathy can trigger social support and ultimately well-being if stimulated across the lifespan, especially since young age; this would help to form the socio-emotional competence across the years, as a sort of cushion that can be useful in the elderly to fulfil active aging.

Atherosclerotic cardiovascular disease, a leading cause of morbidity and mortality worldwide, is a chronic inflammatory disease, linked to a state oxidative stress, with several well-identified culprits, of which low-density-lipoprotein cholesterol (LDL-C) and lipoprotein(a). No specific treatment is currently available to lower lipoprotein(a). It is, therefore, of paramount importance to identify nutritional factors that could lower lipoprotein(a). Growing evidence shows that although reducing saturated fatty acid (SFA) intake decreases LDL-C, it could increase lipoprotein(a). Optimal dietary recommendations may therefore differ depending on an in-dividual’s baseline lipoprotein(a) and LDL-C levels. Assessing the diet-induced true LDL-C response and net balance of these two atherogenic entities is difficult because LDL-C measurement is confounded by lipoprotein(a) cholesterol content. We have estimated, for the first time, the net atherogenic result of diet-induced variations of both LDL-C and lipoprotein(a), thanks to our new concept of LDLapoB risk equivalent=apoB+lp(a)x5 (in nmol/L). This is illustrated, via the rare case of a physician with very high lipoprotein(a) and hypobetalipoproteinemia. She experiences twice a considerable lipoprotein(a) increase (+32%, + 28mg/dL, + 67nmol/L) and higher LDLapoB risk equivalent (138mg/dL versus 123mg/dL) on a mediterranean diet, low in SFA. A reasonable SFA intake, despite causing marginal LDL-C increase, may be advisable in patients with high lipoprotein(a) who need personalized dietary recommendations.

Literature data on Legionella spp. presence in houses water networks have been increasing during the last years, but epidemiological reports assert a high incidence of Legionnaires’ disease infection in Italy. Updating our previously published data, we report a five-year survey on Legionella spp. colonization in 235 buildings with an independent hot water production (IB); 82 buildings with a central hot water production (CB); and 58 buildings with a solar thermal system for hot water production (TB). In all the 375 buildings Legionella spp. was researched in hot and cold water samples and microbiological potability standards of cold water were evaluated. Legionella spp. was detected in 27% of the water networks, mostly in CB and TB. We detected correlations between the presence of bacteria and some physical-chemical parameters (low chlorine level and optimal temperature for Legionella spp. growth). Cold water resulted free from microbiological hazards, except for coliform bacteria isolated in three separate cases, and Legionella spp., detected when cold water temperature was about 20°C. After a five-year survey we confirm the presence of a Legionnaires’ disease risk and the need of training programs for all the workers involved in residential water systems management.

Disease, trauma, and aging account for a significant number of clinical disorders. Regenerative medicine is emerging as a very promising therapeutic option. The design and development of new cell-customized biomaterials able to mimic ECM functionalities represent one of the major strategy to control the cell fate and stimulate tissue regeneration. Recently, hydrogels have received a considerable interest for their use in the modulation and control of cell fate during regeneration processes. Several synthetic bioresponsive hydrogels are being developed in order to facilitate cell-matrix and cell-cell interactions. In this review new strategies and future perspectives of such synthetic cell microenvironment will be highlighted.

The variety of risks due to climate change with a potential impact on Cultural Heritage CH requires a multidisciplinary approach and a preliminary overview of the existing methods for risk analysis and assessment in different fields. Thus, the starting point of the research conducted by the Sapienza PNRR working group consists in a systematic literature review of risk assessment approaches, methods and indicators. As a first outcome, the research has designed a multidisciplinary comprehensive framework consisting of the definition of risk categorization, the framework represented by a measurable index and the main target, according to the classification of Cultural Heritage based on the harmonization of European vocabularies definitions and protocols. The risk assessment framework sets the methodological core of a future multi criteria matrix and digital platform for decision focused on the historic built environment and it is functional to the definition of specific operational guidelines connected to each risk for elaborating descriptive/predictive Architectural Heritage’s transformation scenarios to support the development of mitigation and adaptation strategies.

Although the European reports highlight an increase in community-acquired Legionnaires’ disease cases, the risk of Legionella spp. in private houses is underestimated. In Pisa (Italy) we performed a three-year survey on Legionella presence in 121 buildings with an independent hot water production (IB); 64 buildings with a central hot water production (CB); and 35 buildings with a solar thermal system for hot water production (TB). From all the 220 buildings Legionella spp. was researched in two hot water samples collected either at the recirculation point or at on the first floor and on the last floor, while the potable water quality was analyzed in three cold water samples collected at the inlet from the aqueduct network, at the exit from the autoclave, and at the most remove remote? tap. Legionella pneumophila sg1, Legionella pneumophila sg2-16 and not-pneumophila Legionella species were detected in 26% of the hot water networks, mostly in CB and TB. In these buildings we detected correlations between the presence of Legionella and the total chlorine concentration decrease or/and the increase of the temperature. Cold water resulted free from microbiological hazards, with the exception of Serratia liquefaciens and Enterobacter cloacae isolated at the exit from two different autoclaves. We observed an increase in total microbial counts at 22 and 37°C between the samples collected at the most remote taps compared to the ones collected at the inlet from the aqueduct. The study highlights a condition of potential risk for susceptible categories of population and supports the need for measures of risk assessment and control.

In recent years information and communication technologies (ICT) play a significant role in all aspects of modern society and impact socioeconomic development in sectors as education, administration, business, medical care and agriculture. The benefits of such technologies in agriculture can be appreciated only if farmers use them. In order to predict and evaluate the adoption of these new technological tools, the technology acceptance model (TAM) can be a valid aid. The paper measures the potential acceptance of an e-learning tool designed for EU farmers and agricultural entrepreneurs. Starting from a literature review of the technology acceptance model, by analyzing the most commonly used external variables in the fields of e-learning, Agriculture, and Virtual reality, the analysis shows that computer self-efficacy, individual innovativeness, computer anxiety, perceived enjoyment, social norm, content and system quality, experience and facilitating conditions are the most common determinants addressing technology acceptance. Furthermore, findings evidenced that the external variables have a different impact on the two main beliefs of the TAM Model, Perceived Usefulness (PU) and Perceived Ease of Use (PEOU). This study is expected to bring theoretical support for academics when determining the variables to be included in TAM extensions.

Although the dopamine hypothesis of schizophrenia explains the effects of all the available antipsychotics in clinical use, there is an increasing need for developing new drugs for the treatment of positive, negative, and cognitive symptoms of chronic psychoses. Xanomeline-trospium (KarXT) is a drug combination that is based on the essential role played by acetylcholine in the regulation of cognitive processes and the interactions between this neurotransmitter and other signaling pathways in the central nervous system, with a potential role in the onset of schizophrenia, Alzheimer’s disease, and substance use disorders. A systematic literature review that included four electronic databases (PubMed, Cochrane, Clarivate/Web of Science, and Google Scholar) and the US National Library of Medicine database for clinical trials detected 21 sources referring to 14 studies focused on KarXT, out of which only four have published results. Based on the results of these trials, the short-term efficacy and tolerability of xanomeline-trospium are good, but more data is needed before this drug combination may be recommended for clinical use. However, on a theoretical level, the exploration of KarXT is useful for increasing the interest of researchers in finding new, non-dopaminergic, antipsychotics that could be used either as monotherapy or as add-on drugs.

Background: Interleukin (IL)-33 is a member of interleukin (IL)-1 family of cytokines which has been linked to the development of inflammatory conditions and cancer in the gastrointestinal tract. This study is designed to investigate whether IL-33 has direct effect on human gastric epithelial cells (GES-1) and on human gastric adenocarcinoma cell line (AGS) and gastric carcinoma cell line (NCI-N87), assessing its role in regulation of cell proliferation and cell cycle, apoptosis and necrosis. Cell cycle regulation was also determined in ex vivo gastric cancer samples obtained during endoscopy and surgical procedures. Methods: cell lines and tissue samples underwent stimulation with rhIL-33. Proliferation was assessed by XTT and CFSE assay, we also evaluated apoptosis by Caspase 3/8 Activity assay and Annexin V assays. Cell cycle were analyzed by means of Propidium Iodine assay and gene expression regulation was assessed by RT-PCR Profiling. Results: we found that IL-33 has an antiproliferative and proapoptotic effect on cancer cell line, while it can stimulate proliferation and reduce apoptosis in normal epithelial cell line. These effects are also confirmed by the analysis of cell cycle gene expression which showed a reduced expression of proproliferative genes in cancer cells, in particular genes involved in G0/G1 and G2/M checkpoint. These results are confirmed by the gene expression analysis on surgical and bioptic specimens. Conclusions: the aforementioned results indicate that IL-33 may be involved in cell proliferation in an environment- and cell type-dependent fashion.

An efficient, eco-compatible and very cheap method for the construction of triazoles via eliminative azide–olefin cycloaddition (EAOC) reaction has been developed by a catalytic system IL/FeCl3, offering an highly regioselective approach to structurally diverse 1,5-disubstituted 1,2,3-triazoles in up to 95% yield. This strategy features the reuse of catalytic system through simple operations. Mechanistic studies indicated that an asynchronous concerted dipolar cycloaddition-elimination process might be involved.

Career guidance needs new perspectives considering challenges that characterized our future, and it can not exist without solidarity, inclusion, and attention to the environmental challenges. It also should be able to positively influence stakeholders to invest in the values of the 2030 Agenda recently proposed by the United Nations and their encouragement to think about some emergencies that the new generations will have to face in the future. Based on these premises, we designed and validated a sustainable career guidance intervention for high school students. Participants (N = 75) were assigned to an experimental or a control group. All participants responded pre- and post-intervention to measure career adaptability, training, and future investment, and wishes about the feature. The students from the sustainable career intervention group increased in post-intervention scores on control, curiosity, confidence, and training and future investment. They also indicated future wishes that take into more account attention to relationships and social challenges.

Bacteria can colonize and develop biofilm on a large variety of biotic and abiotic materials, it is accountable for nosocomial infections and chronic illness and consequently, it is a serious economic and public health problem. Staphylococcus epidermidis, thanks to its ability to form biofilm and colonize biomaterials, represents the most frequent causative agent involved in bio-film-associated infections of medical devices. Due to the biofilm presence, S. epidermidis infections are extremely difficult to treat and the research of new molecules able to interfere with its biofilm formation has a remarkable interest. In the present work, the attention was focused on Pseudomonas sp. TAE6080, an Antarctic marine bacterium able to produce and secrete an effective antibiofilm compound. The molecule responsible for this activity was purified by an activity-guided approach and it resulted to be a periplasmic protein, named Cold-Azurin. The Cold-Azurin was recombinantly produced in E. coli and purified. The recombinant protein was able to impair S. epidermidis attachment to the polystyrene surface and effectively prevent biofilm formation.

Glioblastoma (GBM) is the most common primitive tumor in adult central nervous system (CNS), classified as grade IV according to WHO 2016 classification. GBM shows a poor prognosis with an average survival of approximately 15 months, representing an extreme therapeutic challenge. One of its distinctive and aggressive features is aberrant angiogenesis, which drives tumor neovascularization, representing a promising candidate for molecular target therapy. Although several pre-clinical studies and clinical trials have shown promising results, anti-angiogenic drugs have not led to a significant improvement in overall survival (OS), suggesting the necessity of identifying novel therapeutic strategies. Metformin, an anti-hyperglycemic drug of the Biguanides family, used as first line treatment in Type 2 Diabetes Mellitus (T2DM), demonstrated in vitro and in vivo antitumoral efficacy in many different tumors, including GBM. From this evidence, a process of repurposing of the drug has begun, leading to the demonstration of the inhibition of various oncopromoter mechanisms and, consequently, to the identification of the molecular pathways involved. Here, we review and discuss the potential metformin’s antitumoral effects on GBM, inspecting if it could properly act as an anti-angiogenic compound to be considered as a safely add-on therapy in the treatment and management of GBM patients.

Understanding complex biological processes of cells in culture, particularly those related to metabolism, can be biased by culture conditions, since the choice of energy substrate impacts all main metabolic pathways. When glucose is replaced by galactose cells decrease their glycolytic flux, working as an in vitro model of limited nutrient availability. However, the effect of these changes on related physiological processes such as REDOX control is not well documented, particularly in endothelial cells where mitochondrial oxidation is considered to be low. We evaluated the differences in mitochondrial dynamics and function in endothelial cells exposed to galactose or glucose culture medium. We observed that cells maintained in galactose-containing medium show higher mitochondrial oxidative capacity, more fused mitochondrial network, and higher intercellular coupling. These factors are documented to impact the cellular response to oxidative stress. Therefore, we analyzed the levels of two main REDOX regulators and found that Bovine Aortic Endothelial Cells (BAEC) in galactose media had higher levels of FOXO3 and lower levels of Nrf2 than those with glucose in the media. Thus, culture of endothelial cells in galactose containing medium may provide a more suitable condition to study in vitro mitochondrial related processes than glucose media, and deeply influence REDOX signaling in these cells.

A simple procedure to obtain 1,5-disubstituted 1,2,3-triazoles, using the catalytic system erbium(III) trifluoromethanesulfonate, 1-methyl pyridinium trifluoromethanesulfonate and water is described. The reaction proceeds through an eliminative azide–olefin cycloaddition (EAOC) offering a highly regioselective approach and good yields (81–94%). The advantages of this method include simple operations of work-up and the ability of the catalytic system to be re-used five times without an evident loss in yield.

Two antimicrobial agents such as silver nanoparticles (AgNPs) and titanium dioxide (TiO2) have been formulated with natural polysaccharides (chitosan or alginate) to develop innovative inks for the rapid, customizable, and extremely accurate manufacturing of 3D printed scaffolds useful as dressings in the treatment of infected skin wounds. Suitable chemical-physical properties for the applicability of these innovative devices were demonstrated through the evaluation of water content (88-93%), mechanical strength (Young’s modulus 0.23-0.6 MPa), elasticity, and morphology. The antimicrobial tests performed against Staphylococcus Aureus and Pseudomonas Aeruginosa demonstrated the antimicrobial activities against Gram+ and Gram– bacteria of AgNPs and TiO2 agents embedded in the CH or ALG macroporous 3D hydrogels (AgNPs MIC starting from 5 µg/ml). The biocompatibility of chitosan was widely demonstrated by cell viability tests and was higher than that observed for alginate. Constructs containing AgNPs at 10 µg/ml concentration level did not significantly alter cell viability as well as the presence of titanium dioxide; cytotoxicity towards human fibroblasts was observed starting with AgNPs concentration of 100 µg/ml. In conclusions, the 3D printed dressings here developed own the features to be cheap, highly defined, easy to be manufactured and further applied in personalized antimicrobial medicine applications.

The patellofemoral joint (PFJ) is a complex articulation between the patella and the femur, in-volved in the extensor mechanism of the knee. Patellofemoral disorders can be classified into ob-jective patellar instability, potential patellar instability, and patellofemoral pain syndrome. An-atomical factors such as trochlear dysplasia, patella alta, and tibial tuberosity-trochlear groove (TT-TG) distance contribute to instability. Patellofemoral instability can result in various types of dislocations, and the frequency of dislocation can be categorized as recurrent, habitual, or per-manent. Primary patellar dislocation requires diagnostic framing, including physical examina-tion and imaging. Magnetic resonance imaging (MRI) is essential for assessing the extent of damage, such as bone bruises, osteochondral fractures, and medial patellofemoral ligament (MPFL) rupture. Treatment options for primary dislocation include urgent surgery for oste-ochondral fragments or conservative treatment for cases without lesions. Follow-up after treat-ment involves imaging screening and assessing principal and secondary factors of instability. Detecting and addressing these factors is crucial for preventing recurrent dislocations and opti-mizing patient outcomes.

Cardiovascular disease (CVD), a group of disorders affecting the heart or blood vessels, are the primary cause of death worldwide, with an immense impact on patient quality of life and disa-bility. According to the World Health Organization, CVD takes an estimated 17.9 million lives each year, where more than four out of five CVD deaths are due to heart attacks and strokes. In the decades to come, increased prevalence of age-related CVD, such as atherosclerosis, coronary artery stenosis, myocardial infarction (MI), valvular heart disease, and heart failure (HF) will contribute to even greater health and economic burden as the global average life expectancy increases and consequently the world’s population continues to age. Considering this, it is important to focus our research efforts on understanding the fundamental mechanisms underlying CVD. In this review, we focus on cellular senescence and mitochondrial dysfunction, which have long been established to contribute to CVD. We also assess the recent advances in targeting mitochondrial dysfunction and senescence with a focus on therapies that influence both and therefore perhaps represent strategies with the most clinical potential, range, and utility.

The p53 tumor suppressor protein shows antiviral activity. The replication of viruses is also antagonized by interferons (IFNs) – cytokines, which control immunity genes by the STAT transcription factors. The best studied interferons belong to type I (e.g. IFNα) and type II (IFNγ) groups. IFNα and IFNγ both induce activating phosphorylation of STAT1 on Tyr701. Previously, we noticed that p53 activates SOCS1, which is a negative regulator of STAT1 phosphorylation. Thus, we hypothesized that p53 by activating SOCS1 expression reduces phosphorylation of STAT1 and attenuates activation of genes stimulated either by IFNα or IFNγ. To test this hypothesis, we exposed p53-proficient and p53-deficient cells to strong p53 activators, and either to IFNα or IFNγ. Subsequently, we estimated the phosphorylation status of STAT1 and the expression of genes regulated by either of these cytokines. Strong activation of p53 reduced the phosphorylation of STAT1 on Tyr701, however surprisingly it did not lead to reduced expression of most tested interferon-stimulated genes. On contrary, p53 and IFNγ synergized in the activation of CASP1, IFIT1 and IFIT3 genes. We conclude that the interactions between p53 and interferon-activated pathways are more complicated than initially expected, but the apparent cooperation between p53 and IFNγ deserves further studies.

Atrial fibrillation (AF) is an increasingly recognized comorbidity in patients with can-cer. Indeed, cancer patients have a significantly higher incidence of AF than that ob-served in the general population. A reciprocal relationship between these two diseases has been observed, as much as some assume AF as a marker for occult cancer screen-ing, especially in older adults. The pathophysiological mechanisms are many and var-ied, including the underlying pro-inflammatory state, specific treatments (chemo and radiotherapy) and surgery. The therapeutic management of patients with cancer and AF involves the same rhythm and frequency control strategies as the general popula-tion; however, the numerous interactions with chemotherapeutics, which lead to a sig-nificant increase in side effects, as well as the extreme fragility of the patient should be considered. Anticoagulant therapy is also a complex challenge to address, as bleeding and stroke risk scores have not been fully assessed in this subpopulation. Furthermore, in large studies establishing the efficacy of direct oral anticoagulants (DOACs), cancer patients have been underrepresented. In this review, we elaborate on mechanisms linking AF to cancer patients with a particular focus on therapeutic challenges in this population.

Critical sized bone defects and articular cartilage injuries resulting from trauma, osteonecrosis or age-related degeneration are often nonhealing by the physiological repairing mechanisms, thus representing a clinic issue due to the relevant epidemiological incidence. Current treatment approaches consist of autologous or allogenic grafting, which are associated with painfulness, morbidity, risk of infections and rejection. Novel tissue-engineering approaches, aiming at the reconstruction of damaged tissues, have been proposed as alternative solutions to these conven-tional methods. These approaches are based on the combination of three fundamental compo-nents: autologous or allogenic cells, a scaffold and growth-stimulating signals, which are gener-ally referred to as the tissue engineering triad. Three-dimensional polymer networks are fre-quently used as scaffolds to allow cell proliferation and tissue regeneration. In this scenario, cryogels are giving promising results as cell scaffolds over other polymer networks, thanks to their peculiar properties. In particular, cryogels possess an interconnected porous structure and a typical sponge-like behaviour, which facilitate the cellular infiltration and ingrowth. Their properties can be appropriately adjusted to match the requirements of the specific tissue or or-gan that it is intended to regenerate. In this review it is reported the state of the art on the fabri-cation and employment of cryogels in supporting osteo or chondro-genic differentiation for the re-building of more organized tissues. Moreover, it will highlight current progress and future perspectives in the implementation of this technology in the clinical practice.

Toxin/antitoxin (TA) systems are used primarily to inhibit phage, reduce metabolic activity during stress, and maintain genetic elements. Given the extreme toxicity of some of the toxins of these TA systems, we were curious how the cell silences toxins, if the antitoxin is inactivated or when toxins are obtained without antitoxins via horizontal gene transfer. Here we find that the RalR (type I), MqsR (type II), GhoT (type V), and Hha (type VII) toxins are inactivated primarily by a mutation that inactivates the toxin promoter or via the chromosomal mutations iraM and mhpR.

ADHD is a neurodevelopmental disorder that children and also adults can develop. A complex interplay of genetic and environmental factors may underlie interindividual variability in ADHD and potentially related aggressive behavior. Using high-resolution molecular biology techniques, we investigated the impact of some MAOA and SLC6A4 variations on ADHD and aggressive behavior in a group of 80 Italian children with ADHD and in 80 healthy controls.We found that homozygous genotypes of MAOA rs6323 and rs1137070 were associated with an increased risk of ADHD (p=0.02 and p=0.03, respectively), instead the heterozygous genotypes (GT of rs6323 and CT of rs1137030) (p=0.0002 and p=0.0006) were strongly linked to a lower risk of developing this disorder. In patients with aggressive behavior, we highligted only a weak negative association of both MAOA polymorphisms (heterozygous genotypes) with aggressiveness then, suggesting that these genotypes maybe protective towards specific changes in behavior (p=0.05). Interestingly, an increase of the GG genotype of rs6323 (p=0.01) and a decrease of GT genotype (p=0.0005) was also found in patients without aggressive behavior compared with controls. Regarding 5HTT gene genotyping, no allele and genotype differences have been detected among patients and controls. Our work shows that defining a genetic profile of ADHD may help to early detect those patients who are more vulnerable to ADHD and/or antisocial and aggressive behavior and to design precision-targeted therapies.

Individual response to drugs is highly variable and largely influenced by genetic variants and gene-expression profiles. Also, it has been shown that response to drugs is strongly sex-dependent, both in terms of efficacy and toxicity. To expand current knowledge on sex differences in the expression of genes relevant for drug response, we generated a catalogue of differentially expressed human transcripts encoded by 289 genes in 41 human tissues from 838 adult individuals of the Genotype-Tissue Expression project (GTEx, v8 release) and focused our analysis on relevant transcripts implicated in drug response. We have detected significant sex-differentiated expression of 99 transcripts encoded by 59 genes in the tissues most relevant for human pharmacology (Liver, Lung, Kidney, Small intestine terminal ileum, Skin not sun-exposed, and Whole Blood). Among them, as expected, we observed significant differences in the expression of transcripts encoded by the cytochromes in the liver, CYP2B6, CYP3A7, CYP3A5, and CYP1A1. Our systematic investigation on differences between male and female in the expression of drug response related genes, reinforce the need to overcome the sex bias of clinical trials.

Sleep is a fundamental human need: sleep disruption, in fact, causes an increase in the activity of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, metabolic effects, changes in circadian rhythms and pro-inflammatory responses. Sci-entific literature is finally starting to pay attention to the central role of sleep-wake rhythm alterations for patients health. Oxaliplatin is used extensively for the treatment of gastrointestinal cancer and other malignancies, with increased frequency of use in recent years. This study aims to understand the effects of sleep-wake rhythm alterations on health and quality of life on cancer patients treated with oxaliplatin. Study has been conducted through the creation and distribution of questionnaires to patients to inves-tigate the potential alteration of the sleep-wake quality. Evaluating the influence of the collected variables on sleep quality, only liver and biliary tract and pancreas tumor lo-calization, in males, and previous difficulty sleeping, and anxiety, worries and stress, in females, resulted statistically significant. The results obtained may serve as foundation for designing awareness campaigns and updating of patients, healthcare personnel and caregivers, to improve health and quality of patients life.

The ciguatera is a food poisoning caused by the consumption of primarily coral fish; these species exist in large numbers in the seas that bathe the Colombian territory. The underreported diagnosis of this clinical entity has been widely highlighted due to multiple factors, as are among others, ignorance by the primary care practitioner consulted for this condition, clinical similarity with secondary gastroenteric symptoms, to common food poisonings of bacterial, parasitic or viral etiology. Eventually people affected by ciguatotoxin are related to trips to coastal areas hours before the onset of symptoms. Thanks to multiple studies over the years it has been possible to identify the relation of the dinoflagellates in the assembly of said toxin and its introduction into the food chain, starting by fish primarily inhabiting reef ecosystems and culminating in the intake of these by humans. Identifying the epidemiological link, its cardinal symptoms and affected systems such as gastrointestinal, peripheral nervous system and fortunately with a low frequency, the cardiovascular system, leads to a purely clinical diagnostic impression without further complementary studies, performing an adequate treatment primarily symptomatic without underestimating or overlooking any associated complications.

This research examines the impact of social equity on energy consumption. We constructed a digital twin for residential energy consumption by enriching the synthetic population with real-world surveys and feeding them with other environmental and appliance data to the energy modeling framework. We analyzed household hourly energy consumption data from Albemarle County and Charlottesville City in Virginia, USA, for the year 2019. We used clustering analysis to identify patterns in social equity and energy consumption. The results demonstrated the impact of different residential attributes on energy poverty. Statistical analyses, including ANOVA and Chi-Squared tests, were conducted to test for significant differences between racial groups in quantitative and categorical variables. The study found that race is significant in determining the location and quality of housing. People of color often live in areas with higher pollution and less access to green spaces. Additionally, income levels and the age of the house are influential factors in determining energy efficiency. Future work should focus on collecting and analyzing data at the country level and using qualitative data collection methods to gain a more comprehensive understanding of social equity issues concerning energy consumption. Overall, this study provides valuable insights into the relationship between different residential attributes and energy consumption, which can inform policy development to promote more equitable and sustainable communities.

Microplastics are widespread in freshwater environments and could impact these ecosystems. Bivalves are freshwater organisms that are particularly exposed to microplastic contamination. Therefore, in this preliminary study, the accumulation of microplastics, plasticizers, and additives in the freshwater bivalves Anodonta cygnea through active biomonitoring was investigated. Specimens commercially bought were exposed in three rivers in Central Italy for different exposure times: short (1 month) and long (3 months). The gills and the gastrointestinal tract (GIT) were analyzed separately to evaluate the possible uptake and ingestion of particles via Micro-FTIR. For the first time, small microplastics (SMPs, 5-100 µm), plasticizers, additives, and other micro-litter components, e.g., natural and non-plastic synthetic fibers (APFs) were identified in the bivalve A. cygnea. The most abundant polymer in the gills (94.4%), and GITs (66.1%) was polyamide, which had the highest concentration in each river. A decrease in SMPs' abundance was observed over time in the gills in each river, while the abundance in GIT increased. Compared to polymers, a greater variety of APFs was observed in rivers. The APFs changed during the time of exposure and between different rivers more evidently than polymers, allowing a clearer identification of the possible sources. These results highlighted plastic pollution by SMPs using freshwater bivalves as sentinel organisms and the need to investigate further the additives that can be proxies of the presence of microplastics in the environment and biota.

The treatment of critically ill patients remains an evolving and controversial issue. Mechanical circulatory support through a percutaneous approach for the management of cardiogenic shock has taken place in recent years. The combined use of IABP and Impella 2.5 device may have a role to play for this group of patients. A simulation approach may help with a quantitative as-sessment of the achievable degree of assistance. In this paper, we analyse the interaction be-tween Impella 2.5 pump applied as LVAD and IABP using the numerical simulator of the cardi-ovascular system developed in our laboratory. Starting with pathological conditions reproduced using literature data, the simulations were performed setting different rotational speeds for the LVAD and driving the IABP in full mode (1:1) or partial mode (1:2, 1:3 and 1:4). The effects in-duced by drug administration during the assistance were simulated too. The haemodynamic pa-rameters under investigation were: mean aortic pressure, systolic and diastolic aortic pressure, mean pulmonary arterial pressure, mean left and right atrial pressure, cardiac output, cardiac index, left and right ventricular end-systolic volume, left ventricular end-diastolic volume and mean coronary blood flow. The energetic variables considered in the study were: left and right ventricular external work and left and right atrial pressure-volume area. The outcome of our simulations shows that the combined use of IABP and Impella 2.5 achieves adequate support in the acute phase of cardiogenic shock compared to each standalone device. This would allow fur-ther stabilisation and transfer to a transplant centre should escalation of treatment be required.

Among many other themes, Leonardo da Vinci’s Manuscript B contains several drawings of centrally planned churches, some of which are represented using a plan view paired with a bird’s-eye view. The use of a bird’s-eye instead of an elevation represents an innovative depiction technique, which allows to combine the immediacy of the perspective view with the measurability of the façades, and therefore to describe the three-dimensionality of the buildings. To understand the reasons behind the use of this original technique, the edifices’ shape and classify them we decided to use 3D digital reconstruction techniques, for their ability to avoid misunderstandings in the reconstruction process and in the results. This article describes the method to create the digital models of sixteen churches. A Visual programming language (VPL) script was used as 3D base for modelling the churches achieved from a classification code expressing the aggregative rules of the churches. Then, the geometric process for the construction of the plan and its relationship with the elevation measures was studied for each church. Finally, this information was used for the completion of the 3D models, distinguishing more output variants each time there was an inconsistency between plan and perspective view, a variability of one architectural element or an uncertainty.

This paper presents a study about the integration of Piezoelectric Energy Harvesting Systems (PE-EHS) in building envelopes for powering Fiber Bragg Grating (FBG) sensors, enabling efficient and low-consumption monitoring with the objective to leverage Structural Health Monitoring (SHM). The research includes preliminary tests conducted in a real environment to validate the PE-EHS when fully integrated into the façade, capturing mechanical vibrations generated mainly by wind loads. Based on these activities, the final configuration of PE-EHS is defined to provide a complete system for façade monitoring. This integrated system includes the Piezoelectric Generator (PEG), Supercapacitor (SC), Power Conditioner Circuit (PCC), Fibre Optic Sensing (FOS) Interrogator, and the IoT Gateway trans-mitting measurement data within an Internet of Things (IoT) monitoring platform. This configuration is tailored to address the challenges related to the structural integrity of building envelopes. Results demonstrate a potential for a stand-alone solution in the façade sector, but, raising issues for certain limitations, requiring further investigation. In particular, the study emphasizes constraints related to the energy production of PE-EHS for façade integration. It highlights the necessity to carefully consider these limitations within the broader context of their applicability, providing insights for the informed deployment of Piezoelectric Energy Harvesting technology in building envelope monitoring.

Background The main aim of reconstructive surgery (RS) is to restore the integrity of soft tissues damaged by trauma, surgery, congenital deformity, burns or infection. Microsurgical techniques consist of harvesting tissues that are separated from the vascular sources of the donor site and anastomosed to the vessels of the recipient site. In these procedures, there are some preoperative modifiable factors that have the potential to influence the outcome of the flap transfer and its anastomosis. Methods Chronic inflammatory anaemia (ACD) is a constant condition in patients who have undergone RS and correlates with the perfusion of the free flap. In RS, it is important to maintain good tissue oxyporesis, avoiding blood hyperviscosity. From January 2017 to September 2019, we studied 16 patients (16 males, mean age 38 years) who underwent microsurgical procedures for RS. Haemoglobin (Hb) levels, Corpuscular Indexes, Transferring saturation (TSAT) ferritin concentrations and creatinine clearance have been measured the first day after surgery (T0), after the first week (T1) and after five weeks (T2). At T0 all patients showed low hemoglobin levels (average 7.4 g/dl, STD 0,71range 6,2-7,4 g dL-1), with an MCV of 72, MCH 28, MCHC 33, RDW 16, Sideremy 35, Ferritin 28, Ret% 1,36, TRF 277 and Creatinine Clearance 119. . We assessed all patients for clinical status, medical history and comorbidities before starting therapy. Results. In collaboration between the two departments, we started a therapeutic protocol with erythropoietic stimulating agents (ESAs) (Binocrit 6000 UI/week) and intravenous iron every other day, on the second day after surgery. Thirteen patients received ESAs and FCM (500-1000 mg per session), three patients received ESAs and iron gluconate (1 vial every other day). No patients received blood transfusions. No side effects were observed and, most importantly, no limb or flap rejection. Conclusions Preliminary data from our protocol show an optimal therapeutic response in a surgical setting with limited data in the scientific literature. The enrolment of further patients will allow us to validate this therapeutic protocol with statistically significant data.

Polyarteritis nodosa (PAN), also known as panarteritis nodosa, represents a form of necrotizing vasculitis that predominantly affects medium-sized vessels, although it is not restricted to them and can also involve smaller vessels. The clinical presentation is heterogeneous and characterized by a significant number of patients exhibiting general symptoms including asthenia, fever, and unintended weight loss. Although PAN can involve virtually any organ, it preferentially affects the skin, nervous system, and the gastrointestinal tract. Orchitis is a rare but specific manifestation of PAN. The absence of granulomas, glomerulonephritis and ANCA serves to distinguish PAN from other type of vasculitis. Major complications consist of hemorrhagic and thrombotic events occurring in mesenteric, cardiac, cerebral, and renal systems. Historically, PAN was frequently linked to hepatitis B virus (HBV) infection, but this association has dramatically changed in recent years due to declining HBV prevalence. Current epidemiological research often identifies connection between PAN and genetic syndromes as well as neoplasia. This article provides a comprehensive review of PAN, specifically focusing on the progression of its clinical manifestations over time.

GDF5 gene is involved in the development of skeletal elements, synovial joint formation, tendons, ligaments, and cartilage. Several polymorphisms are present within the gene and two of them, rs143384 and 143383, have been reported as correlated with osteoarticular disease or muscle flexibility. The aim of this research is to verify if the worldwide distribution among human populations of rs143384 polymorphism has been shaped by selective pressure, or if it’s the result of random genetic drift events. Ninety-four individuals of both sexes, 18-28 years old, from Sardinia were analyzed. We observed the following genotype frequencies: 28.72% of homozygotes AA, 13.83% of homozygotes GG, and 57.45% of heterozygotes AG. Allele frequencies were 0.574 for allele A and 0.426 for alle G. Relationships between populations were verified by Multidimensional Scaling (MDS). Our data show: i) a clear heterogeneity within the African populations; ii) a strong differentiation between Africans and the other populations: iii) the Sardinian population is placed withing the European cluster. To reveal possible traces of selective pressure, Population Branch Statistic (PBS) was calculated; both SNPs rs143384 and 143383 have low PBS values, suggesting that there are no signals of selective pressure in those areas of the gene.

21-hydroxylase deficiency (21OHD), the most common form of congenital adrenal hyperplasia (CAH), is associated with pathogenic variants in CYP21A2 gene. The clinical form of the disease ranges from classic or severe to non-classic (NC) or mild late onset. The CYP21A2 gene is located on the long arm of chromosome 6, within the RCCX region, one of the most complex loci in the human genome. The 3’untranslated sequence of CYP21A2 exon 10 overlap the last exon of TNXB gene (these genes lie on the opposite strands of DNA and have the opposite transcriptional direction) that encodes an extracellular matrix glycoprotein tenascin-X (TNX). A recombination event between TNXB and its pseudogene TNXA causes a 30-kb deletion producing a chimeric TNXA/TNXB gene (CAH-X chimera) where both CYP21A2 and TNXB genes are impaired. This genetic condition characterizes a subset of patients with 21OHD who display the hypermobility phenotype of Ehlers Danlos Syndrome (hEDS) (CAH-X Syndrome). The aim of this study was to assess the prevalence of CAH-X syndrome in an Italian cohort of patients with 21OHD. At this purpose, 196 probands were recruited. Multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing were used to identify the CAH-X genotype. Twenty-one individuals showed the heterozygous continuous deletion involving the CYP21A2 and part of the TNXB gene. EDS-related clinical manifestations were identified in most patients carrying the CAH-X chimera. A CAH-X prevalence of 10.7% was estimated in our population.

The meridian line is a basic instrument for positional astronomy, it was used to study the motion of Sun, Moon, planets and the position of stars by measuring position and time of their passage through the meridian plane. The accuracy of such positions was dependent on precise theories of the atmospheric refraction (Cassini, 1655 and Laplace, 1825) and by the use of reference marks present originally on the meridian line, and now cancelled by the centuries. From October 27, 2018 the new pinhole of the meridian line in the Basilica of S. Maria degli Angeli in Rome (1702) is a circle 25 mm wide and 6.11 mm thick and its position is fixed, in order to perform a series of observations of astrometric quality, the IGEA campaign. The comparison of the observed positions of the meridian passages of the Sun, Southern and Northern limbs, with the ephemerides of Calsky.org and Stellarium 0.20.2 for the Sun are examined for the dates of the ingresses into the zodiacal signs, when the ecliptic longitude is exactly 0°/180° (Aries and Libra, spring and fall equinox), 30°/150° (Taurus, Virgo), 60°/120° (Gemini, Leo), 90° (Cancer), 330°/210° (Pisces, Scorpio), 300°/240° (Aquarius/Sagittarius), 270° (Capricorn). The former geometrical calibration of the marks present on the line, with a total station, is compared with another calibration done with a metal and laser meter. The first star on the floor of the Basilica representing the position of the Sun on August 20, 1702 when the pope Clement XI visited the meridian line, financed by him, has been calibrated with the solar image. The present pinhole is 4.4±0.1 mm South with respect to the original one of 1702.

The onset of neurodegenerative diseases involves a complex interplay of pathological mecha-nisms, including protein aggregation, oxidative stress, impaired autophagy. This review focuses on the intricate connection between oxidative stress and autophagy in neurodegenerative disor-ders, highlighting autophagy as pivotal in disease pathogenesis. Reactive oxygen species (ROS) play dual roles in cellular homeostasis and autophagy regulation, with disruptions of redox sig-naling contributing to neurodegeneration. The activation of the Nrf2 pathway represents a criti-cal antioxidant mechanism, while autophagy maintains cellular homeostasis by degrading al-tered cell components. The interaction between p62/SQSTM1, Nrf2 and Keap1 forms a regulatory pathway essential for cellular stress response, whose dysregulation leads to impaired autophagy and aggregate accumulation. Targeting the Nrf2-p62/SQSTM1 pathway holds promise for thera-peutic intervention, mitigating oxidative stress and preserving cellular functions. Additionally, the review explores the potential synergy between the endocannabinoid system and Nrf2 signal-ing for neuroprotection. Further research is needed to elucidate the involved molecular mecha-nisms and develop effective therapeutic strategies against neurodegeneration.

The removal of metal ions by biosorption on inexpensive materials is still a challenge for environmental engineering research. In this study, marine green algae biomass (Ulva lactuca sp.) and the biochars obtained from this biomass, at 320 C (BC-320) and 550 C (BC-550), were used as biosorbents for the removal of Cu(II) ions from aqueous solution. In addition to comparing the biosorption capacities, the determination of the thermodynamic parameters allows the choice of the most suitable material for the biosorption processes. The experimental results, obtained for Cu(II) ions biosorption on each biosorbent (algae biomass (AB), BC-320 and BC-550), at three different temperatures (10, 30 and 50 C) were analyzed using Langmuir and Freundlich isotherm models, while pseudo-first order, pseudo-second order and intra-particle diffusions models were used to model the kinetic data. The biosorption of Cu(II) ions is best described by the Langmuir model and the pseudo-second kinetic model, regardless of the type of biosorbent. The maximum biosorption capacity (qmax, mg/g) depends on the temperature, but also on the type of biosorbent, and follow the order: BC-320 < AB < BC-550. Using the experimental isotherms, the thermodynamic parameters (G0, H0 and S0) for the biosorption of Cu(II) ions on each biosorbent were calculated. The analysis of the obtained values constitutes the main arguments in choosing BC-550 as the most effective biosorbent for the removal of Cu(II) ions from aqueous media.

Climate variability and change has been found to be one of the factors that affect economies leading to food insecurity in various parts of the world. Kenya is no exception. This study looks at how climate variability has contributed to food insecurity in Kisii County, Kenya. The objectives of this study is therefore to, (i) to examine the rainfall and temperature trends in Kisii County for a period of approximately 30 years, (ii) to examine the effect of climate variability on food production and (iii) to assess the perception of local farmers on weather and climate information, (iv) to evaluate the coping strategies adopted at to bridge the gap on food deficit at different household level and (v) to assess the nutritional status of children and the elderly. The study was conducted in two sub-counties of Kisii County; Marani and Bomachoge Chache. The data used was mainly rainfall and temperature data from meteorological stations and sample data gathered from selected groups. The study population comprised of children between 6 months and 59 months, household heads, elderly people and agricultural officers. Purposive sampling was used to select agricultural officers while multistage sampling was used to select respondents at household level. Data was collected by use of a pre-tested questionnaire. The MUAC tape was used to collect nutritional status of children while BMI data was obtained from elderly people. Mann Kendall statistic was used to determine whether the trend of rainfall and temperature observed is significant while Chi-square test was used to determine whether the coping strategies observed varied significantly at household level. From the analysis, rainfall has not shown any significant change in Kisii County while temperature trend has been significantly increasing over the years at 95% confidence level. This could explain the observed reduction in river levels. Analysis of crop production and price trends of major food crops in Kisii County showed a decreasing trend of food production leading to increase in price over the years. This meant that farmers could not produce enough to take them to the next harvesting season making farmers to adopt different coping strategies at household level which differed significantly according to Chi-Square test. Malnutrition status of both elderly people above 59 years and children between 6-59 months were similar with 23% of both children/elderly being severely malnourished/malnourished. This study has only looked at climatic factors such as rainfall and temperature. Other aspects such as depth of underground water, ph level of soil and the effects of land fragmentation also need to be looked at. This study is important to both farmers in choosing the right crop to plant, and policy makers and planners in formulating the best mitigation and intervention strategies for Kisii County food insecurity problem. This will further contribute to national efforts towards achievement of vision 2030.

Wearable sensors have become increasingly popular for assessing athletic performance, but the optimal methods for processing and analysing the data remain unclear. This study investigates the efficacy of discrete and continuous feature extraction methods, separately and in combination, for modelling countermovement jump performance using wearable sensor data. We demonstrate that continuous features, particularly those derived from Functional Principal Component Analysis, outperform discrete features in terms of model performance, robustness to variations in data distribution and volume, and consistency across different datasets. Our findings underscore the importance of methodological choices, such as signal type, alignment methods, and model selection, in developing accurate and generalisable predictive models. We also highlight the potential pitfalls of relying solely on domain knowledge for feature selection and the benefits of data-driven approaches. Furthermore, we discuss the implications of our findings for the broader field of sports biomechanics and provide practical recommendations for researchers and practitioners aiming to leverage wearable sensor data for athletic performance assessment. Our results contribute to the development of more reliable and widely applicable predictive models, facilitating the use of wearable technology for optimising training and enhancing athletic outcomes across various sports disciplines.

The COVID-19 pandemic had a wide-ranging impact, resulting in a global recession due to weakened purchasing power. This circumstance necessitates business organizations adapting to developments and being more conscious of the risk of financial statement fraud. The intention of this research is to investigate the way corporate governance affected financial statement fraud during the COVID-19 pandemic. To acquire empirical data for examining corporate governance variables on financial statement fraud, the research was examined using quantitative methods. The study takes advantage of secondary data acquired from annual reports of companies under special monitoring listed on the Indonesia Stock Exchange of 2020-2021. The logistic regression method was used to evaluate 134 data sets, and financial statement fraud was measured using the Z-Score and F-Score models. The results indicate that using the Z-score, only the board size has a negative effect on financial statement fraud during the COVID- 19 pandemic. Meanwhile, using the F-Score, the corporate governance variables studied are not proven to have an influence on financial statement fraud during the COVID 19 pandemic.

Intense physical efforts performed at maximal or near-maximal speeds and the ability to recover among sprint are important characteristics of soccer player. Considering that women's soccer is a markedly growing sport, the aim of the study was to analyse the performance (total time –TT-; fatigue index percentage -IF%) and physiological (aerobic and anaerobic) responses to Repeated Sprint Ability Test (RSA, 7×30 m sprints with 25 s of active recovery among sprints) in an elite female player (age: 30 yrs; BMI: 20.3 kg/m²). A repeated measure MANOVA over the 7 sprints time series was applied (p < 0.05). Results showed that TT was 58.71 s (Ideal Time: 56.98 s) with IF% of 3.0%. Energy contributions were given for 80.3% by aerobic, 19.2% by anaerobic lactid, and 0.5% by anaerobic alactid sources. Considering that 1) we have different kinetics in heart rate (HR) and maximum oxygen uptake with oxygen uptake that reach the peak when HR is still rising, and 2) the energy consumption during intermittent exercises requires different metabolism as a result of physiological stimuli proposed, the present findings substantiate the need to choose specific and adequate training methods for female soccer players that aim at increasing their RSA performances.

Gastric cancer is an aggressive disease with increasing global incidence in recent years. Human epidermal growth receptor 2 (HER2) is overexpressed in approximately 10-20% of gastric cancers. The implementation of targeted therapy against HER2 as part of the standard of care treatment in metastatic disease has improved the prognosis of this subset of patients. However, gastric cancer still has high mortality rates and urgently requires new treatment strategies. The combination of immunotherapy with HER2-targeted therapies has shown synergistic effects in preclinical models, being the rationale behind exploring this combination in clinical trials in locally advanced and metastatic settings. Additionally, the irruption of antibody-drug conjugates and other novel HER2-targeted agents has led to the development of numerous clinical trials showing promising results. This review presents the molecular mechanisms supporting the use of HER2-targeted drugs in combination with immunotherapy and provides an overview of the therapeutic scenario of HER2-positive disease. We focus on the role of immunotherapy but also summarize emerging therapies and combinations under clinical research that may change the standard treatment in HER-2 positive disease in the future.

The objective of this study was to analyze the in vitro stability and toxicity of liposomes containing guarana in skin cell lines. The liposomes were produced by the reverse phase evaporation method containing 1 mg/mL guarana. The stability of the liposomes was evaluated by physical-chemical parameters for up to 90 d using three different storage conditions. The cytotoxicity of guarana (GL), liposomes (B-Lip), and guarana-loaded liposomes (G-Lip) was evaluated on spontaneously immortalized human keratinocyte cell lines (HaCaT), murine swiss albino fibroblasts (3T3), and human fibroblast (1BR.3.G). The evaluation was performed using cellular viability analysis. The techniques used were 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red capturing (NRU) and the analyses were conducted after 24, 48, and 72 h exposure of these cells to the different treatments. The G-Lip exhibited physical-chemical stability for 60 d when the samples were stored in a refrigerator. The GL, B-Lip, and G-Lip demonstrated low cytotoxicity in the three cell cultures tested since a low reduction in cell viability was only observed at the highest concentrations. In addition, greater cell damage was observed for B-Lip; however, guarana protects cells from this damage. Thus, G-Lip structures can be considered as promising systems for topical applications.

This paper details the comprehensive activities conducted in a laboratory setting to assess the Structural Health Monitoring (SHM) of prefabricated building envelopes. Aimed at enhancing the structural evaluation of buildings, the focus of this research lies in employing nondestructive sensors for SHM with the objective to advance in the understanding and assessment of facade conditions. The paper outlines the methodologies employed, starting with a modal analysis to define the structural vibration's modal frequency. Subsequently, tests were defined and executed to validate building envelope compliance in case of stress typical of high-rise building. Throughout these tests, continuous monitoring of the façade was conducted using both conventional (accelerometers, extensimeter washers) and non-conventional sensors (Fiber Optic Sensing) The gathered data underwent thorough processing and analysis to provide an overall perspective on the structure's behavior during the stress test. The investigation aimed to identify whether specific physical phenomena correlate with distinct signals and to evaluate if continuous façade monitoring over the building's lifespan aids in preventing potential structural damage. Moreover, two modal analyses were conducted to compare final data and frequencies with earlier data, enabling the detection of any structural alterations. The results from compliance testing and structural analysis yielded noteworthy insights contributing to the evolving field of structural health monitoring, offering valuable findings that advance our ability to proactively manage and maintain the integrity of building structures.

Despite the recent approval of novel immunotherapies, as immunomodulatory drug, proteasome inhibitors and anti-CD38 monoclonal antibodies, Multiple Myeloma (MM) remains incurable and the acquisition of triple-refractoriness leads to really dismal outcomes, in even earlier lines of therapy. More recently, innovative therapeutic strategies targeting B cell maturation antigen (BCMA), highly expressed on the plasma cell surface, are drawing different future landscapes in terms of effectiveness and outcomes. Belantamab Mafodotin, a first-in-class anti-BCMA antibody drug conjugates, demonstrated good efficacy and safety profile in triple-refractory patients in the phase 2 DREAMM-2 trial and it was approved for the treatment of MM triple-exposed patients with >4 prior lines of therapy. Here, starting from Belantamab Mafodotin clinical trials also exploring combination studies and different schedules in order to improve its efficacy and toxicity, we focused on real life experiences all over the world, which have confirmed clinical trial data and encourage further Belantamab Mafodotin investigations

The p53 tumor suppressor protein is an activator of transcription. Diverse stress factors lead to various sets of posttranslational modifications of p53 what results in different sets of upregulat-ed genes. We noticed that actinomycin D and nutlin-3a (A+N) synergize in inducing activating phosphorylations of p53 and upregulation of selected p53-target genes. Here we found that one of these genes is DUSP13, which codes for poorly-studied, dual-specificity phosphatase having at least two isoforms, one expressed in testis and the other in skeletal muscles. In cancer cells ex-posed to A+N, DUSP13 is expressed from an alternative promoter in intron, what results in ex-pression of isoform named TMDP-L1. The luciferase reporter tests demonstrated that this pro-moter is activated by both endogenous and ectopically expressed p53. We showed for the first time that mRNA expressed from this promoter actually produces the protein, which can be de-tected by Western blotting in all examined cancer cell lines with wild-type p53 exposed to A+N. In some cell lines it is also induced by clinically relevant camptothecin or by nutlin-3a acting alone. This isoform, fused with green fluorescent protein localizes in perinuclear region of cells. Thus, TMDP-L1 isoform may be an important element of p53-regulated stress response system.

The core components of regenerative medicine are stem cells with high self-renewal and tissue regeneration potentials. Adult stem cells can be obtained from many organs and tissues. NANOG, SOX2 and OCT4 represent the core regulatory network that suppresses differentiation-associated genes, maintaining the pluripotency of mesenchymal stem cells. The roles of NANOG in maintaining self-renewal and undifferentiated status of adult stem cells are still not perfectly established. In this study we define the effects of downregulation of NANOG in maintaining self-renewal and undifferentiated state in mesenchymal stem cells (MSCs) derived from subcutaneous adipose tissue (hASCs). hASCs were expanded and transfected in vitro with short hairpin Lentivirus targeting NANOG. Gene suppressions were achieved at both transcript and proteome levels. The effect of NANOG knockdown on proliferation after 10 passages and on the cell cycle was evaluated by proliferation assay, colony forming unit (CFU), qRT-PCR and cell cycle analysis by flow-cytometry. Moreover, NANOG involvement in differentiation ability was evaluated. We report that downregulation of NANOG revealed a decrease in the proliferation and differentiation rate, inducing cell cycle arrest by increasing p27/CDKN1B (Cyclin-dependent kinase inhibitor 1B) and p21/CDKN1A(Cyclin-dependent kinase inhibitor 1A) through p53 and regulate DLK1/PREF1. Furthermore, NANOG induced downregulation of DNMT1, a major DNA methyltransferase responsible for maintaining methylation status during DNA replication probably involved in cell cycle regulation. Our study confirms that NANOG regulates the complex transcription network of plasticity of the cells, inducing cell cycle arrest and reducing differentiation potential.

Acute lymphoblastic leukemia (ALL) is a blood cancer that primarily affects children but also adults. It is due to the malignant proliferation of lymphoid precursor cells that invade the bone marrow and can spread to extramedullary sites. ALL is divided into B cell (85%) and T cell lineages (10 to 15%); rare cases are associated with the natural killer (NK) cell lineage (<1%). To date, the survival rate in children with ALL is excellent while in adults continues to be poor. Despite the therapeutic progress, there are subsets of patients that still have high relapse rates after chemotherapy or hematopoietic stem cell transplantation (HSCT) and an unsatisfactory cure rate. Hence, the identification of more effective and safer therapy choices represents a primary issue. In this review, we will discuss novel therapeutic options including bispecific antibodies, antibody-drug conjugates,chimeric antigen receptor (CAR)-based therapies, and other promising treatments for both pediatric and adult patients.

The present study is the second step (concerning the normal-diet restoration) of the our previous one (concerning the calcium-free diet) to determine whether the normal-diet restoration, with/without concomitant PTH(1-34) administration, can influence amounts and deposition sites of the total bone mass. Histomorphometric evaluations and immunohistochemical analysis for Sclerostin expression were conducted on the vertebral bodies and femurs in rat model. The final goals are: i) to define timing and manners of bone mass changes when calcium is restored in the diet; ii) to analyze the different involvement of the two bony architectures having different metabolism (i.e. trabecular versus cortical bone); iii) to verify the eventual role of PTH(1-34) administration. Results evidenced the greater involvement of the trabecular bone with respect to the cortical one, in answering to different calcium diet content, and the effect of PTH mostly in the recovery of trabecular bony architecture. The main findings emerged from the present study are: i) the importance of the interplay between mineral homeostasis and skeletal homeostasis in modulating and guiding bone answers to dietary/metabolic alterations and ii) the evidence that the more involved bony architecture is the trabecular one, the most susceptible to the dynamical balance of the two homeostases.

Historically, admission of hematological patients in the ICU shortly after the start of a critical illness is associated with better survival rates. Early intensive interventions administered by MET could have a role in the management of hematological critically ill patients, eventually reducing ICU admission rate. In this retrospective and monocentric study, we evaluate the safety and effectiveness of intensive treatments administered by the MET in a medical ward frame. The administered interventions were mainly helmet CPAP and pharmacological cardiovascular support. Frequent reassessment by the MET at least every 8 to 12 hours was guaranteed. We analyze data from 133 hematological patients that required MET intervention. In hospital mortality was 38%; mortality doesn’t increase in patients not immediately transferred to the ICU. Only 3 patients died without a former admission in ICU; in these cases, mortality was not related to the acute illness. Moreover, 37% of patients overcame the critical episode in the hematological ward. Higher SOFA and MEWS scores were associated with a worst survival rate, while neutropenia and pharmacological immunosuppression were not. The MET approach seems to be safe and effective. SOFA and MEWS confirmed to be effective tools for prognostication.

As β-glucosidases represent the major bottleneck for industrial degradation of plant biomass, great efforts are being devoted both to discover novel and robust versions of these enzymes, as well as to develop efficient and inexpensive ways to produce them. In this work, raw glycerol from chemical production of biodiesel was tested as carbon source for the fungus Talaromyces amestolkiae with the aim of producing enzyme cocktails rich in this activity. Approximately 11 U/mL β-glucosidase were detected in these cultures, constituting the major cellulolytic activity. Proteomic analysis revealed BGL-3 as the most abundant protein and the main β-glucosidase. This enzyme crude was successfully used to supplement a basal commercial cellulolytic cocktail (Cellu-clast 1.5L) for saccharification of pretreated wheat straw, corroborating that even hardly exploitable industrial wastes, such as glycerol, can be used as secondary raw materials to produce valuable enzymatic preparations in a framework of circular economy

Abstract: Background: Vasoplegic shock syndrome(VSS) after an off-pump coronary artery bypass graft (OPCABG) is an extremely rare condition. Inotropic support is usually the first-line therapy though it can precipitate several complications or be ineffective. We report the first case of severe refractory VSS after OPCABG successfully treated with hydroxycobalamin. Methods: A 77-year-old gentleman underwent OPCABG for three vessels coronary artery disease. Preoperative LV ejection fraction was 28%, and the patient before surgery started sacubi-tril/valsartan titrated, then, to the highest dose. Surgery was uneventful and, by the end of the procedure, TEE showed improved biventricular contractility. Results: The patient was transferred to the ICU without inotropic support but he developed soon hypotension. TEE ruled out pericardial tamponade and confirmed fair contractility. Norepineph-rine was titrated to a medium-high dose, vasopressin was started and a Swan-Ganz catheter was placed. SVR was 480 dyn·s·cm−5. Despite aggressive pharmacologic treatment (including Methylprednisolone and Methylene blue), no improvements were noticed. 10 g of hydroxycobalamin were administered. One hour later hemodynamic status re-assessment showed SVR > 800 dyn·s·cm−5. Afterward, vasopressors were gradually reduced. Conclusions: Our case demonstrated the importance of adequate early treatment in VSS after OPCABG. For the first time, hydroxycobalamin was effectively used to restore homeostasis.

Background: Patients with Inflammatory Bowel Disease (IBD) believe that diet is a key factor in the pathogenesis of their disease and in worsening their symptoms; they often follow restrictive diets that can lead to malnutrition, anxiety, and stress. Recent studies have found an association between eating disorders and IBD, particularly anorexia nervosa and ARFID (Avoidant Restrictive Food Intake Disorder). None of these studies report the association with orthorexia nervosa, that is the obsession with healthy and natural foods. Aim: to assess the risk of orthorexia nervosa in patients with IBD. Methods: 158 consecutive subjects were recruited, including 113 patients diagnosed with IBD and 45 controls. The Donini standardized questionnaire ORTO-15 was administered to assess the risk of orthorexia; clinical and demographic data were also collected. Results: patients with IBD have a prevalence of orthorexia of 77%, significantly higher than the 47% observed in the control group. In patients with IBD, the risk of orthorexia is associated with lower BMI and history of previous surgery. Conclusion: Many patients with IBD develop orthorexia nervosa that impacts the patient's psychological and social sphere, exposes them to a high risk of nutritional deficiencies, and affects quality of life. Further high quality studies are warranted to evaluate the clinical impact of orthorexia and its correlation with clinical features and frank eating disorders.

Porcine Circovirus 2 (PCV2) vaccines are based on either inactivated whole virion, or recombinant ORF2 capsid protein assembled into Virus-like Particles (VLPs). No data are available instead about the immunizing properties of free, non-assembled capsid protein. To investigate this issue, ORF2 of a reference PCV2b strain was expressed in a Baculovirus-based expression system without assembly into VLPs. The free purified protein was formulated into an oil vaccine at three distinct Ag payloads: 10.8 / 3.6 / 1.2 micrograms /dose. Each dose was injected intramuscularly into five, 37-day old piglets, carefully matched for maternally-derived antibody. Five control piglets were injected with sterile PBS in oil adjuvant. Twenty-eight days later, all the pigs were challenged intranasally with 200,000 TCID50 of PCV2b strain DV6503. After challenge infection, all the pigs remained in good clinical conditions. The recombinant vaccine did not induce significant antibody and PCV2-specific IFN-gamma responses. ELISPOT and lymphocyte proliferation data confirmed poor induction of cell-mediated immunity. In terms of PCV2 viremia, there was no significant difference between vaccinated and control animals. The histological data indicated the absence of a detectable viral load and of PCVAD lesions in both vaccinated and control animals, as well as of histiocytes and multi-nucleated giant cells. We conclude that free, non-assembled ORF2 capsid protein does not induce protective immunity.

In the area of dental healthcare services, where patients and professionals deal with multiple auditory stimuli, this cross-sectional study reports on the intricate dynamics of sound preferences, noise obstacles, and the profound impact of music on anxiety reduction within dental office set-tings. The sample comprises of 134 dental patients, primarily females (56.7%), with varying age groups, education levels, and therapy durations in the university clinics of the department of Dentistry, National and Kapodistrian University of Athens and four private dental offices at the metropolitan area of Athens, Greece. Notably, 92.5% of the participants report no hearing loss, and 56.7% exhibit some level of noise sensitivity. The study reveals a moderate to good perceived health status (M=3.84, SD=0.95) among participants, with low perceived noise disturbance in university dental clinics. Preferences for instrumental music, foreign pop, and classical music are prominent during waiting times. Potential irritations include impersonal treatment (44%) and staff behavior (41.8%). Music player usage within the settings of the dental clinic involves radios (49.3%) and headphones (41.0%). Correlations and predictors indicate associations between health status, music preferences, and noise disturbances. More specifically, visiting the university dental clinics (β = .300, p = .005) as well as younger age (β = .300, p = .034) were significant predictors of better perceived health status. Clearer perception of external sounds while using the music player (β = .190, p = .039) was a significant predictor of better perceived health status, while poorer health was predicted by the preference of Greek folk songs (β = -.200, p = .030). Also, the use of smartphones for playing music was related to poorer health (β = -.370, p < .001). Following, younger age (β = -.270, p = .015), lower education (β = -.210, p = .035), higher noise sensitivity (β = .190, p = .027), as well as feelings of anxiety and nervousness due to ambient noise from people and machines (β = .510, p = .027) were significant predictors of noise disturbance from machines. Also, visiting private clinics (β = .240, p = .018), preferences of specific playlist (β = .310, p = .012), no music (β = .280, p = .016) and use of smartphones to play music (β = .230, p = .029) were significant predictors of noise disturbance from patients or staff. Finally, the preference of listening to a specific playlist was related to better health status (r = .190, p < .05). Findings aim to optimize eco-soundscapes in dental offices, con-tributing to enhanced patient well-being. The research underscores the potential of music inter-ventions to alleviate dental anxiety and improve the overall dental experience and quality care.

Atrial fibrillation (AF) is an increasingly recognized comorbidity in patients with cancer. Indeed, cancer patients have a significantly higher incidence of AF than that observed in the general population. A reciprocal relationship between these two diseases has been observed, as much as some assume AF as a marker for occult cancer screening, especially in older adults. The pathophysiological mechanisms are many and varied, including the underlying pro-inflammatory state, specific treatments (chemo and radiotherapy) and surgery. The therapeutic management of patients with cancer and AF involves the same rhythm and frequency control strategies as the general population; however, the numerous interactions with chemotherapeutics, which lead to a significant increase in side effects, as well as the extreme fragility of the patient should be considered. Anticoagulant therapy is also a complex challenge to address, as bleeding and stroke risk scores have not been fully assessed in this subpopulation. Furthermore, in large studies establishing the efficacy of direct oral anticoagulants (DOACs), cancer patients have been underrepresented. In this review, we elaborate on mechanisms linking AF to cancer patients with a particular focus on therapeutic challenges in this population.

HIV infection is well-known to be associated with the development of Hodgkin's lymphoma (HL) with extranodal involvement being exclusive bone marrow involvement is less common. Co-infection by other viruses such as the esptein Baar virus (EBV) increases the incidence of a frequent complication denominated hemophagocytic lymphohistocytosis (HLH). We present the case of a 50-year-old patient with the above clinical spectrum who develops several serious complications during treatment.

Von Hippel-Lindau disease (VHL) is a multiple organ neoplastic syndrome with autosomal dominant transmission, complete penetrance, and variable expression caused by mutations in the VHL gene. Although VHL disease is hereditary in many cases, new mutations cause up to 20 % of the incidence. Mutations in VHL may cause the development of cysts and tumors in many organs, including brain and spinal cord hemangioblastoma, renal cell carcinoma (RCC), retinal heman-gioblastoma (RH), pheochromocytoma, epididymal and broad ligament cystadenomas, endo-lymphatic sac tumor, pancreatic neuroendocrine tumors, and renal and pancreatic cysts. VHL is a syndrome associated with functional inactivation of the Von Hippel–Lindau protein (pVHL). pVHL is a tumor suppressor mainly known for its role as a regulator of hypoxia-inducible factor (HIF) activity. The prevalence of VHL disease is between 1 in 39 000 and 1 in 91 000 individuals in different regional populations. Here, we review the etiology, epidemiology, pathophysiology, genetics, clinical manifestations, diagnosis, and current treatments, as well as the molecular aspects of this disease. We also discuss the animal models used to study this disease, VHL biomarkers, and current VHL clinical trials for VHL according to NIH.

Injury to the peritoneum during surgery is followed by a healing process that frequently results in the attachment of adjacent organs by a fibrous mass, referred to commonly as adhesions. Because injuries to the peritoneum during surgery are inevitable, one must understand the mechanisms of adhesion formation to prevent its occurrence. This requires a thorough understanding of the molecular sequence that results in the attachment of injured peritoneum and the development of fibrous tissue. Recent data show that fibroblasts from the injured peritoneum may play a critical role in forming adhesion tissues. Therefore, identifying changes in gene expression patterns in the peritoneal fibroblasts during the process may provide clues to the mechanisms by which adhesion develops. This review presents many papers discussing genes implied in peritoneal adhesion.

This scoping review investigated how consumers perceive and interpret serving size information on food packages. A search of seven databases (2010 to September 2017) was followed by title and abstract screening, with relevant articles assessed for eligibility in full-text. Fourteen studies met inclusion criteria, with relevant data extracted by one reviewer and checked for consistency by a second reviewer. Five studies reported poor understanding of nutrition facts labelling and portion size, with information to ‘benchmark’ serving size against reported as helpful in two studies. Consumer attitudes towards serving size labelling were measured in six studies and identified that serving size information was interpreted as indicative of nutrient intake regardless of portion size recommendations. Increased labelled serving sizes resulted in increased portion sizes in three studies, with three studies reporting the opposite or neutral effect for discretionary food portion sizes. The influence of labelled serving size on consumer attitudes and consumption is complex and sometimes counterintuitive. As labelled serving size can impact on consumption, any changes may result in unintended public health consequences. The effects of labelled serving size format changes should be tested carefully within experimental and ecological contexts and accompanied by tailored, comprehensive and serving size-specific food literacy initiatives.

The IgM and IgT classes were previously identified and characterized in the Antarctic teleost Trematomus bernacchii, a species belonging to the Perciform suborder Notothenoidei. Herein we characterized the gene encoding the polymeric immunoglobulin receptor (pIgR) in the same species and compared it to pIgR of multiple teleost species belonging to five perciform sub-orders, including 11 Antarctic and one non-Antarctic (Cottoperca gobio) notothenioid species, the latter living in less cold periantarctic sea. Antarctic pIgR genes displayed particularly long in-trons marked by sites of transposable elements and transcription factors. Furthermore, analysis of T. bernacchii pIgR cDNA unveiled multiple amino acid substitutions unique to Antarctic species, all introducing adaptive features, including N-glycosylation sequons. Interestingly, C. gobio shared most features with the other perciforms rather than with the cold adapted relatives. T. bernacchii pIgR transcripts were predominantly expressed in mucosal tissues, as indicated by q-PCR and in situ hybridization analysis. These results suggest that in cold adapted species pIgR preserved its fundamental role in mucosal immune defense, although remarkable gene structure modifications occurred.

A Life Cycle Analysis was performed considering three existing power plants of comparable size operating with different sources of renewable energy: geothermal, solar and wind. Primary data were used for building the life cycle inventories. The geothermal power plant includes emissions treatment for removal of hydrogen sulfide and mercury. The scenario about the substitution of natural emissions from geothermal energy, with specific reference to the greenhouse effect, is also investigated performing a sensitivity analysis. The results are characterized employing a wide portfolio of environmental indicators employing the Recipe 2016 and the ILCD 2011 Midpoint+ methods; normalization and weighting are also applied using the Recipe 2016 method at endpoint level. The results demonstrate a good eco-profile of geothermal power plant with respect to other renewable energy systems and allow for a critical analysis to support potential improvements of the environmental performances.

Cutaneous lymphocytosis (CL) is an uncommon and controversial lymphoproliferative disorder described in dogs and cats. CL is generally characterized by a heterogeneous clinical presentation and histological features that may overlap with epitheliotropic lymphoma. Therefore, its neoplastic or reactive nature is still debated. Here, we describe clinicopathological, immunohistochemical and clonality features of a retrospective case series of 19 cats and 10 dogs with lesions histologically compatible with CL. In both species, alopecia, erythema and scales were the most frequent clinical signs. Histologically, a dermal infiltrate of small to medium-sized lymphocytes, occasionally extending to the subcutis, was always identified. Conversely, when present, epitheliotropism was generally mild. In cats, the infiltrate was consistently CD3+; in dogs, a mixture of CD3+ and CD20+ lymphocytes was observed only in 4 cases. The infiltrate was polyclonal in all cats, while BCR and TCR clonal rearrangements were identified in dogs. Overall, cats had a long-term survival (median overall survival=1080 days) regardless of the treatment received, while dogs showed a shorter and variable clinical course, with no evident associations with clinicopathological features. In conclusion, our results support a reactive nature of the disease in cats, associated with prolonged survival; despite a similar histological picture, canine CL was associated with a more heterogeneous lymphocytic infiltrate, clonality results, and response to treatment.

The involvement of macular function in its preganglionic elements, during the neurodegenerative process of multiple sclerosis (MS), is controversial. In this case-control observational and retrospective study, we assessed multifocal electroretinogram (mfERG) responses from 41 healthy Controls, 41 relapsing-remitting MS patients without optic neuritis (ON) (MS-noON Group), 47 MS patients with ON: 27 with full recovery of high-contrast best corrected visual acuity (BCVA) (MS-ON-G Group) and 20 with poor recovery of BCVA (MS-ON-P Group). MfERG N1 and P1 implicit times (ITs), and N1-P1 response amplitude densities (RADs) were measured from concentric rings (R) with increasing foveal eccentricity: 0-5° (R1), 5-10° (R2), 10-15° (R3), 15-20° (R4), 20- 25° (R5), and from retinal sectors [superior, nasal, inferior and temporal] between 0-15° and 0- 25°. In MS-ON-P Group, mean mfERG RADs detected from R1 (0-5°) and from the central nasal quadrant (0-15°) were significantly reduced (p<0.01) with respect to those of Control, MS-noON and MS-ON-G Groups. No other significant differences between Groups for any mfERG parameters were found. Our results suggest that in MS, exclusively after ON with poor recovery of BCVA, the neurodegenerative process can induce dysfunctional mechanisms involving photoreceptors and bipolar cells of the fovea and of the more central nasal macular area.

Our work is regarding the analysis of land use changes, in the light of “saving soil” against the expansion due to unearned plus value of land: The loss of natural and agricultural surface in front of the expanding urban environment is a critical aspect of unsustainability of urban development, especially in the way it was carried out in the past decades. The measure of the physical transition of land use and characters from a more natural condition of land surface to a new artificial one, joint with a parallel analysis of the increase of land value due to such change is nowadays a major land-policy tool. The interplay of urban economics regulation with planning, reveals new key issues in urban governance and environmental preservation. In this paper it will be shown some experiment about the impact assessment of soil take, related with the seek of valorization of property inside the planning process. Our paper reports as well about the experimental activity carried out inside the MITO Lab of the Polytechnic of Bari, where reports about property values and environmental values have been produced, specially looking at the reality of the Apulia, a southern Italian Region, that is rich of farmlands and coastlines, often invaded by constructions with a severe loss of nature, landscape and ecosystems services.

Shiga toxin (Stx) produced by Escherichia coli is the main pathogenic factor of diarrhea-associated hemolytic uremic syndrome (HUS), which is characterized by obstruction of renal microvasculature by platelet-fibrin thrombi. It is well known that the oxidative imbalance generated by Stx induces platelet activation, contributing to thrombus formation. Moreover, activated platelets release soluble CD40 ligand (sCD40L) which in turn contributes to oxidative imbalance, triggering the release of reactive oxidative species (ROS) on various cellular types. The aim of this work was to determine if the interaction between the oxidative response and platelet-derived sCD40L participates in the pathogenic mechanism during HUS. Activated human glomerular endothelial cells (HGEC) by Stx2 induced platelets to adhere to them. Although platelet adhesion did not contribute to endothelial damage, high levels of sCD40L were released to the medium. The release of sCD40L by activated platelets was inhibited by antioxidant treatment. Furthermore, we found increased levels of sCD40L in plasma from HUS patients, which were also able to trigger the respiratory burst in monocytes, in a sCD40L-dependent manner. Thus, we concluded that platelet-derived sCD40L and the oxidative response are reciprocally stimulated during Stx2-associated HUS. This process may contribute to the evolution of glomerular occlusion and the microangiopathic lesions.

Women in science, technology, engineering, and mathematics (STEM) fields are under-represented, and women are also less likely than men to be in leadership positions generally. Little is known about the intersection of these areas: women in leadership in STEM. To determine what sort of barriers and assistance female STEM leaders have encountered, a survey was developed asking women who are in academic leadership positions in STEM about their experiences. The main barriers were similar in the STEM area and in leadership: balancing work/home life, devaluing of achievements, and imposter syndrome. The main two types of assistance in both STEM and leadership were support from spouse/partner, and encouragement from peers. The main barriers women encounter are cultural and will take time to overcome. The main assistance women have had comes from people, not training or institutional structures.

Motivated by the increasing need of optimised micro-devices for droplets production in medical and biological applications, this paper introduces an integrated approach for the study of the liquid-liquid droplet creation in flow-focusing micro cross-junctions. The micro-junction considered is characterised by a restriction of the channels cross-sections in the junction, which has the function of focusing the flow in the region of the droplet formation. The problem is studied numerically in OpenFOAM environment and validated by the comparison with experimental results obtained by high-speed camera images and micro-PIV measurements. The analysis of the forces acting on the dispersed phase during the droplet formation and the diameter of the droplets obtained numerically are considered for the development of a model of the droplet breakup under the squeezing regime. On the basis of energy balancing during the breakup, a relation between interfacial tension, the size of the cross-sections in the junction, and the time interval needed for droplet creation is obtained, which yields a novel correlation between the dimensionless length of the droplet and the dimensionless flow rate. This correlation is general and can be used to predict the droplet diameters produced by similar micro-junctions with different aspect ratios and extended to different geometries of flow-focusing micro-junctions.

Selenoproteins are a group of proteins containing selenium in the form of selenocysteine (Sec, U) as the 21st amino acid coded in the genetic code. Their synthesis is dependent on dietary selenium uptake and a common set of cofactors. Selenoproteins accomplish diverse roles in the body and cell processes by acting, for example, as antioxidants, modulators of the immune function, detoxification agents for heavy metals, and other xenobiotics, key compounds in thyroid hormone metabolism. Although the functions of all this protein family are still unknown, several disorders in their structure, activity or expression have been described by researchers. They concluded that selenium or cofactors deficiency, on one hand, or the polymorphism in selenoproteins genes and synthesis, on the other hand, are involved in a large variety of pathological conditions, including type 2 diabetes, cardiovascular, muscular, oncological, hepatic, endocrine, immuno-inflammatory, neurodegenerative diseases. This review is focused on specific roles in medicine only of selenoproteins that are each named after an alphabet letter, less known than the rest of them, regarding their implications in patho-logical processes of several prevalent diseases and also in disease prevention.

Tuberculosis (TB) remains the leading cause of death from a single infectious agent. Among children, TB can have a wide range of non-specific clinical and radiological manifestations becoming a challenging diagnosis, particularly in areas with a low prevalence. We present the case of a 14 month-old female with a history of fever of unknown origin (FUO) and later diagnosed with miliary tuberculosis.

Kidneys of mice, rats and humans possess progenitors that maintain daily homeostasis and take part in endogenous regenerative processes following injury, owing to their capacity to proliferate and differentiate. In the glomerular and tubular compartments of the nephron, consistent studies demonstrated that well-characterized, distinct populations of progenitor cells, localized in the parietal epithelium of Bowman capsule and scattered in the proximal and distal tubules, could generate segment-specific cells in physiological conditions and following tissue injury. However, defective or abnormal regenerative responses of these progenitors can contribute to pathologic conditions. The molecular characteristics of renal progenitors have been extensively studied, revealing that numerous classical and evolutionarily conserved pathways, such as Notch or Wnt/β-catenin, play a major role in cell regulation. Others, such as retinoic acid, renin-angiotensin-aldosterone system, TLR2 (Toll-Like Receptor 2) and leptin, are also important in this process. In this review, we summarize the plethora of molecular mechanisms directing renal progenitor responses during homeostasis and following kidney injury. Finally, we will explore how single cell RNA sequencing could bring the characterization of renal progenitors to the next level, while knowing their molecular signature is gaining relevance in the clinic.

Background: The Liver Imaging Reporting and Data System (LI-RADS) combines standardized terminology with a classification system for imaging findings in patients with HCC, therefore rendering diagnostic biopsy unnecessary in many cases. This retrospective study included 23 patients with a biopsy diagnosis of HCC, performed either before or after local interventional procedures, in order to evaluate the histopathologic changes induced by previous procedures and their potential influence on the response to immune therapy. Material and Methods: The study encompassed a cohort of patients diagnosed with Hepatocellular Carcinoma (HCC). Diagnosis was established through contrast-enhanced computer tomography or magnetic resonance imaging that identified LI-RADS-5 nodules in conjunction with historical liver disease and elevated alpha-fetoprotein (AFP) levels, or through histological examination confirming positivity for glypican3, heat shock protein70, and glutamine synthetase. The study detailed the liver disease etiology, LI-RADS scores, characteristics and dimensions of HCC nodules, serum AFP concentrations, Edmondson-Steiner grading, and the expression of programmed cell death ligand 1 (PD-L1) in the tumor cells. Results: Among the study's cohort of Hepatocellular Carcinoma (HCC) patients, a portion had not received any prior treatments, while the remainder experienced local HCC recurrence following trans-arterial chemoembolization or radiofrequency ablation. Observations indicated elevated alpha-fetoprotein (AFP) levels in those who had not undergone any previous interventions, showing statistical significance. The Edmondson-Steiner classification predominantly identified grade III differentiation across patients, irrespective of their treatment history. Furthermore, an increase in intra-tumoral programmed cell death ligand 1 (PD-L1) expression was noted in patients who had not been subjected to previous therapies. Conclusion: Liver biopsy offers valuable insights for patients with Hepatocellular Carcinoma (HCC), assisting in the tailoring of immune therapy strategies, particularly in cases of recurrence following prior local interventions.

Animal welfare remains a very important issue in the livestock sector but monitoring animal welfare in an objective and continuous way remains a serious challenge. Monitoring animal welfare based upon physiological measurements instead of audio-visual scoring of behaviour would be a step forward. One of the obvious physiological signals related to welfare and stress is heart rate. The objective of this research was to measure heart rate (beat per minutes) on pigs with technology that soon will be affordable. Affordable heart rate monitoring is done today at large scale on humans using the Photo Plethysmography (PPG) technology. We used PPG sensors on pig’s body to test whether it allows getting reliable heart rate signal. A continuous wavelet transform (CWT)-based algorithm is developed to decouple the cardiac pulse waves from the pig. Three different wavelets, namely 2^nd, 4^th and 6^th order Derivative of Gaussian (DOG, are tested. We show results of the developed PPG-based algorithm against electrocardiograms (ECG) as a reference measure for heart rate and this for an anesthetized versus a non-anesthetised animal. We tested three different anatomical body positions (ear, leg and tail) and give results for each body position of the sensor. In summary, it can be concluded that the agreement between PPG-based heart rate technique and reference sensor goes from 91 to 95 percentage. In this paper we showed the potential of using the PPG-based technology to assess pig’s hear rate.

Antibiotic failure is one of the most worrying health problems worldwide. Nowadays we are facing an international crisis where several issues are involved: new antibiotics are not being discovered any longer, resistance mechanisms become spread in nearly every clinical isolate of bacteria and the appearance of recurrent infections caused by persistent bacteria complicates the overcoming of infections. In this context, it has been explored new anti-infectious strategies against MDR and persistent bacteria as well as the rescue of FDA-approved compounds (drug repurposing). Among the highlighted new anti-infectious strategies we find anti-microbial peptides, anti-virulence compounds, phage therapy and new molecules. On the other hand, as drugs of repurposing that have been described, we have anti-inflammatory compounds, anti-psychotics, anti-helmintic drugs, anti-cancerous and statins.

Italian Directives recommends the good quality of natural mineral waters but literature data assert a potential risk from several microorganisms colonizing wellsprings and mineral water bottling plants. Aim of study is the identification of microorganisms from spring waters (SW) and bottled mineral waters (BMW) samples. Methods: Routine microbiological indicators, Legionella spp., Nontuberculous mycobacteria (NTM), protozoa (FLA) and physical-chemical parameters were assessed in 24 SW and 10 BMW samples performing culture methods and molecular tests as PCR and qPCR. Results: In 33 out of 34 samples no cultivable bacteria were isolated with the exception of 83 CFU/L of Mycobacterium gilvum, detected in one warm rich-mineralized SW. qPCR showed the presence of Legionella genomic units in 24% of samples (mean 2,9x10²±1,7x10² GU/L) and NTM genomic units in 18% of samples (mean 5,7x10^3±4,1x10³ GU/L). Vermamoeba vermiformis and Acanthamoeba polyphaga were recovered respectively in 70% of BMW samples (counts from 1,3x10³ to 1,2x10⁵) and 42% of SW samples (counts from 1,1x10³ to 1,3x10⁴). Vahlkampfia spp. was detected in 42% of SW and 70% of BMW samples (mean 1,3x10⁴ ±2,9x10³ GU/L). Conclusion: The study highlights a low rate of microbial risk and the importance of risk assessment in natural mineral waters.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Cardiac rehabilitation (CR) has proven to be effective in reducing the rate of recurrence and disease as secondary prevention (evidence-based intervention) in patients who have suffered from myocardial infarction (MI). CR is a multidisciplinary path in which the patient is followed pharmacologically, from a psychological, nutritional, nursing and physiotherapy point of view. Post-MI patients present a reduction in the performance of the diaphragm muscle, the main inspiratory muscle, and this condition can become a risk factor for further relapses or for the onset of heart failure. Despite the solidity of the international guidelines for CR, the latter are lacking in specifically indicating an evaluation and training path regarding the inspiratory muscles in post-MI patients who have not undergone cardiac surgery. The article reviews the information on the adaptation of the diaphragm post-MI and highlights the need for clearer indications for a rehabilitation process that gives importance to the diaphragm.

The crosstalk between gut microbiota, intestinal epithelial cells, and innate and adaptive immune system governs the maintenance of the intestinal homeostasis. Any interference in this tight dialogue and in the processes preserving cellular homeostasis (e.g., autophagy) may dysregulate the immune response and impair the clearance of harmful bacteria favoring the dysbiotic alteration of the microbic flora that leads to chronic inflammation. Gut dysbiosis is strongly associated with gastrointestinal inflammatory disorders, among them the inflammatory bowel disease (IBD). This review discusses the current knowledge on IBD, from the genetic background of high-risk patients to the molecular mechanisms underlying the disease, the contribution of the microbic flora, and the role of autophagy in intestinal epithelial cells and provides the state of art regarding the targeted-nutritional approaches aimed to restore the beneficial crosstalk between an “anti-inflammatory” microbiota and the host. Analysis of the molecular pathogenesis of IBD will help identify genetic and diet-associated risk factors and thus suggest personalized strategies to prevent and manage the disease to improve quality of life with long-term maintenance of the remission phase.