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Inherited peripheral neuropathies (IPNs) are a group of diseases associated with mutations in various genes with fundamental roles in the development and function of peripheral nerves. Over the past 10 years, significant advances in identifying molecular disease mechanisms underlying axonal and myelin degeneration, acquired from cellular biology studies and transgenic fly and rodent models, have facilitated the development of promising treatment strategies. However, no clinical treatment has emerged to date. This lack of treatment highlights the urgent need for more biologically and clinically relevant models recapitulating IPNs. For both neurodevelopmental and neurodegenerative diseases, patient-specific induced pluripotent stem cells (iPSCs) are a particularly powerful platform for disease modeling and preclinical studies. In this review, we provide an update on different in vitro human cellular IPN models, including traditional two-dimensional monoculture iPSC derivatives, and recent advances in more complex human iPSC-based systems using microfluidic chips, organoids, and assembloids.

Abstract Inherited peripheral neuropathies (IPNs) are a group of diseases associated with mutations in various genes with fundamental roles in the development and function of peripheral nerves. Over the past 10 years, significant advances in identifying molecular disease mechanisms underlying axonal and myelin degeneration, acquired from cellular biology studies and transgenic fly and rodent models, have facilitated the development of promising treatment strategies. However, no clinical treatment has emerged to date. This lack of treatment highlights the urgent need for more biologically and clinically relevant models recapitulating IPNs. For both neurodevelopmental and neurodegenerative diseases, patient-specific induced pluripotent stem cells (iPSCs) are a particularly powerful platform for disease modeling and preclinical studies. In this review, we provide an update on different in vitro human cellular IPN models, including traditional two-dimensional monoculture iPSC derivatives, and recent advances in more complex human iPSC-based systems using microfluidic chips, organoids, and assembloids.

The global threat of antimicrobial resistance (AMR) is now increasingly recognized for the danger posed by its environmental spread. Aquatic environments and wastewater represent a significant diffusion and selection pathway for antibiotic resistance genes and antibiotic resistant bacteria (ARGs and ARBs). During a collaborative hackathon event, the “Innovation Workshop on Water Quality Monitoring & Assessment,” held in September 2023, experts addressed four challenges related to water quality, including the challenge of globalization AMR surveillance in water. This paper, derived from the workshop findings, proposes a globally adaptable model for antimicrobial resistance surveillance intended as an advance to improve future monitoring systems. The new framework aims to address significant challenges, such as the lack of standardized methodological approaches or lack of funding, coordination, and awareness across a short-, medium- and long-term plan, integrating sustainability concepts, extending participation and monitoring capacity of countries, and offering efficient solutions. This vision is first articulated by creating a technical committee that promotes awareness of antimicrobial resistance and develops a single data management and communication platform. Subsequently, by developing local, national, and international policies, centralized laboratories will be established at the regional level, and built based on existing realities. These laboratories will include facilities to make the management of analyses more efficient, from sampling to reporting the final result. In the long term, activities that allow the maintenance of the created framework and continuous technological development and advancement will be promoted. All this will be achieved in collaboration with national and supranational bodies that are already addressing the issue at a global level.

Background: Biomarkers development for prognostication or prediction of perioperative myocardial disease is critical for the evolution of treatment options in patients undergoing cardiac surgery. The aim of our prospective monocentric study was to investigate the role of selenoprotein 1 (SEEP 1) as a potential biomarker for assessing the risk of myocardial injury after cardiac surgery. Methods: Circulating SEPP1 was measured in the blood of 45 patients before surgery and at 4 h, 8 h and 12 h after CPB by enzyme-linked immunosorbent assay (ELISA); (3) Results: circulating SEPP-1 levels measured 4 h after surgery were strongly correlated with CK-MB levels measured at 48 h (R = 0.598, p < 0.0001) and at 72 h (R = 0.308, p = 0.05). Close correlations were also found between 4 h SEPP-1 and Hs-c troponin values measured at 24 h (R = 0.532, p < 0.0001), 48 h (R = 0.348, p = 0.01) and 72 h (R = 0.377, p = 0.02), as well as with cardiopulmonary bypass (CPB) (R = 0.389, p = 0.008) and cross-clamp time (R = 0.374, p = 0.001); (4) Conclusions: Early SEPP1 measurement after CPB may hold great potential for identifying cardiac surgery patients at risk of developing perioperative myocardial injury.

Abstract Background and Aims In the post-hoc analyses of the SUSTAIN and ASSURE trials (Kidney Blood Press Res. 2018;43:449-457), Apabetalone, an epigenetic modulator which lowers serum alkaline phosphatase (AlkPhos), stabilized the GFR in patients with cardiovascular disease and a GFR

Several studies have detected SARS-CoV-2 in the stool of infected people as in urban wastewater. The quantification of SARS-CoV-2 in wastewater appears today as a powerful tool that can help in wastewater-based epidemiology (WBE). The goal is to improve the prediction of new waves of COVID-19 outbreaks and provide an early warning of the evolution of the infection. In this research, we highlighted some practical and scientific aspects that emerged during an extensive ongoing monitoring campaign carried out on a large number of wastewater treatment plants located in the province of Trento (North Italy) and aimed at the detection of SARS-CoV-2 in raw municipal wastewater. The open issues underline are related to the collection and storage (sampling protocol, storage and heat treatment), to the molecular analysis (enrichment phase), and to the mathematical calculation of SARS-CoV-2 load in wastewater, suitable for WBE (standard curve to obtain the concentration of genomic units and flow rate measurements). This study provides some insights that can help in the implementation of surveillance plans in other regions. HIGHLIGHTS It is possible to quantify SARS-COV-2 from wastewater.; Wastewater based epidemiology is a useful tool for predicting new outbreaks.; Heat treatments make the virus more easily detectable.; Several storage protocols have been tested.;

Although the gut microbiota is known to affect body weight, its relationship with overweight/obesity is unclear. Our aim was to characterize microbiota composition in a cohort from the southernmost area of Italy. We investigated whether an altered gut microbiota could play an etiological role in the pathogenesis of overweight/obesity. A total of 163 healthy adults were enrolled. Microbiome analysis was performed via 16S rRNA gene sequencing. We found significant phylum variations between overweight (N = 88) and normal-weight (N = 75) subjects. Bacteroidetes and Proteobacteria were higher in overweight participants (p = 0.004; p = 0.03), and Firmicutes and Verrucomicrobia were lower (p = 0.02; p = 0.008) compared to normal-weight participants. Additionally, Akkermansia and Bifidobacterium (genus level) were significantly lower in the overweight group, as well as Akkermansia muciniphila at the species level. The Firmicutes/Bacteroidetes ratio (F/B ratio), an index of dysbiosis, was found to be inversely associated with BMI in linear and logistic regression models (p = 0.001; p = 0.005). The association remained statistically significant after adjustment for potential confounders. This cross-sectional study contributes to defining the gut microbiota composition in an adult population living in southern Italy. It confirms the relationship between overweight susceptibility and the dysbiosis status, highlighting the possible etiological role of the F/B ratio in disease susceptibility.

Surgical bypass is the gold standard treatment in patients affected by chronic limb-threatening ischemia in advanced GLASS stages, according to the Global Vascular Guidelines. For patients in whom an autologous graft is not available, a prosthesis could be used with the adjunct of a distal arteriovenous fistula interposition. The aim of this study was to examine the long-term results of below-the-knee surgical revascularization using a prosthesis with the distal adjunct mentioned above. From 2010 to 2020, we performed 159 lower limb below-the-knee surgical revascularizations using a prosthesis with the creation of an arteriovenous fistula interposition on the distal anastomosis. The GLASS stage was 3 in 100% of patients. The primary patency rates were as follows: 86.7% at 1 year, 57.2% at 3 years, and 12.6% at 5 years. The graft thrombosis rates were 17.4% at 1 year, 42.1% at 3 years, and 64.5% at 5 years. The amputation-free survival rates were 79% at 1 year, 76% at 3 years, and 64% at 5 years. PTFE prosthetic bypass for below-the-knee arteries using an arteriovenous fistula interposition is a good solution in patients without an autologous conduit. This technique offers reasonable graft patency and limb salvage rates.

Although scalp defects can vary in size and thickness, scalp avulsion represents a rare occurrence. This type of lesion may have different origins, but it is usually related to long hair being caught in agricultural machinery. The management of full-thickness scalp defects poses a challenge to the head and neck surgeon due to the possible involvement of neurovascular structures and scar retraction, which can affect the esthetic restoration of the area. Several algorithms for the choice of scalp reconstruction have been proposed in the literature and different techniques are available for extensive scalp defect reconstruction (local soft tissue flap, microvascular free flap, and skin graft combined with dermal substitutes), based upon the scalp defect type. Here we describe six cases of patients with total scalp avulsion, which required a combined reconstruction with a split-thickness skin graft (STSG) and Integra® matrix immediately after the trauma.

Background: Biomarkers development for prognostication or prediction of perioperative myocardial disease is critical for the evolution of treatment options in patients undergoing cardiac surgery. The aim of our prospective monocentric study was to investigate the role of selenoprotein 1 (SEEP 1) as a potential biomarker for assessing the risk of myocardial injury after cardiac surgery. Methods: Circulating SEPP1 was measured in the blood of 45 patients before surgery and at 4 h, 8 h and 12 h after CPB by enzyme-linked immunosorbent assay (ELISA); (3) Results: circulating SEPP-1 levels measured 4 h after surgery were strongly correlated with CK-MB levels measured at 48 h (R = 0.598, p < 0.0001) and at 72 h (R = 0.308, p = 0.05). Close correlations were also found between 4 h SEPP-1 and Hs-c troponin values measured at 24 h (R = 0.532, p < 0.0001), 48 h (R = 0.348, p = 0.01) and 72 h (R = 0.377, p = 0.02), as well as with cardiopulmonary bypass (CPB) (R = 0.389, p = 0.008) and cross-clamp time (R = 0.374, p = 0.001); (4) Conclusions: Early SEPP1 measurement after CPB may hold great potential for identifying cardiac surgery patients at risk of developing perioperative myocardial injury. [ABSTRACT FROM AUTHOR]

Abstract Background Multiple Sclerosis (MS) is an immune-mediated inflammatory disease of the Central Nervous System (CNS) which damages the myelin sheath enveloping nerve cells thus causing severe physical disability in patients. Relapsing Remitting Multiple Sclerosis (RRMS) is one of the most common form of MS in adults and is characterized by a series of neurologic symptoms, followed by periods of remission. Recently, many treatments were proposed and studied to contrast the RRMS progression. Among these drugs, daclizumab (commercial name Zinbryta), an antibody tailored against the Interleukin-2 receptor of T cells, exhibited promising results, but its efficacy was accompanied by an increased frequency of serious adverse events. Manifested side effects consisted of infections, encephalitis, and liver damages. Therefore daclizumab has been withdrawn from the market worldwide. Another interesting case of RRMS regards its progression in pregnant women where a smaller incidence of relapses until the delivery has been observed. Results In this paper we propose a new methodology for studying RRMS, which we implemented in GreatSPN, a state-of-the-art open-source suite for modelling and analyzing complex systems through the Petri Net (PN) formalism. This methodology exploits: (a) an extended Colored PN formalism to provide a compact graphical description of the system and to automatically derive a set of ODEs encoding the system dynamics and (b) the Latin Hypercube Sampling with PRCC index to calibrate ODE parameters for reproducing the real behaviours in healthy and MS subjects.To show the effectiveness of such methodology a model of RRMS has been constructed and studied. Two different scenarios of RRMS were thus considered. In the former scenario the effect of the daclizumab administration is investigated, while in the latter one RRMS was studied in pregnant women. Conclusions We propose a new computational methodology to study RRMS disease. Moreover, we show that model generated and calibrated according to this methodology is able to reproduce the expected behaviours.

Epithelial splicing regulatory proteins 1 and 2 (ESRP1/2) control the splicing pattern during epithelial to mesenchymal transition (EMT) in a physiological context and in cancer, including breast cancer (BC). Here, we report that ESRP1, but not ESRP2, is overexpressed in luminal BCs of patients with poor prognosis and correlates with estrogen receptor α (ERα) levels. Analysis of ERα genome-binding profiles in cell lines and primary breast tumors showed its binding in the proximity of ESRP1 and ESRP2 genes, whose expression is strongly decreased by ERα silencing in hormone-deprived conditions. The combined knock-down of ESRP1/2 in MCF-7 cells followed by RNA-Seq, revealed the dysregulation of 754 genes, with a widespread alteration of alternative splicing events (ASEs) of genes involved in cell signaling, metabolism, cell growth, and EMT. Functional network analysis of ASEs correlated with ESRP1/2 expression in ERα+ BCs showed RAC1 as the hub node in the protein–protein interactions altered by ESRP1/2 silencing. The comparison of ERα- and ESRP-modulated ASEs revealed 63 commonly regulated events, including 27 detected in primary BCs and endocrine-resistant cell lines. Our data support a functional implication of the ERα-ESRP1/2 axis in the onset and progression of BC by controlling the splicing patterns of related genes.

Background: Acute Kidney Injury (AKI) is a frequent, dangerous complication in patients undergoing cardiopulmonary bypass (CPB) with oxidative stress playing a crucial role. In this pilot study we evaluated the possible role of the selenoprotein-p1 (SEPP1), a circulating, anti-oxidant selenium transporter, as a predictive biomarker of AKI in this population setting. Methods: Circulating SEPP1 was measured in the blood of 45 patients before surgery and at 4 h, 8 h and 12 h after CPB by Enzyme-Linked Immunosorbent Assay (ELISA). Results: SEPP1 increased from 69 [IQR 39–85] to 3263 [IQR 1886.2–5042.7] ng/mL (p for trend