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•HBV covalently closed circular DNA (cccDNA) is responsible for viral persistence decades after liver disease resolution.•A latent occult HBV infection is identified by the presence ...of the antibody to the HB-core antigen (anti-HBc).•We developed a highly sensitive droplet digital PCR assay for intrahepatic HBV cccDNA quantitation.•HBV cccDNA is detectable and quantifiable in 27 out of 100 anti-HBc-positive liver donors.•Serum anti-HBc IgG levels are associated with the finding of intrahepatic HBV cccDNA.
The accurate diagnosis of occult hepatitis B virus (HBV) infection (OBI) requires the demonstration of HBV DNA in liver biopsies of hepatitis B surface antigen-negative individuals. However, in clinical practice a latent OBI is deduced by the finding of the antibody to the hepatitis B core antigen (anti-HBc). We investigated the true prevalence of OBI and the molecular features of intrahepatic HBV in anti-HBc-positive individuals.
The livers of 100 transplant donors (median age 68.2 years; 64 males, 36 females) positive for anti-HBc at standard serologic testing, were examined for total HBV DNA by nested-PCR and for the HBV covalently closed circular DNA (HBV cccDNA) with an in-house droplet digital PCR assay (ddPCR) (Linearity: R2 = 0.9998; lower limit of quantitation and detection of 2.4 and 0.8 copies/105 cells, respectively).
A total of 52% (52/100) of the individuals studied were found to have OBI. cccDNA was found in 52% (27/52) of the OBI-positive, with a median 13 copies/105 cells (95% CI 5–25). Using an assay specific for anti-HBc of IgG class, the median antibody level was significantly higher in HBV cccDNA-positive than negative donors (17.0 7.0–39.2 vs. 5.7 3.6–9.7 cut-off index COI, respectively, p = 0.007). By multivariate analysis, an anti-HBc IgG value above 4.4 COI was associated with the finding of intrahepatic HBV cccDNA (odds ratio 8.516, p = 0.009); a lower value ruled out its presence with a negative predictive value of 94.6%.
With a new in-house ddPCR-based method, intrahepatic HBV cccDNA was detectable in quantifiable levels in about half of the OBI cases examined. The titer of anti-HBc IgG may be a useful surrogate to predict the risk of OBI reactivation in immunosuppressed patients.
The covalently closed circular DNA (cccDNA) form of the hepatitis B virus (HBV) sustains the persistence of the virus even decades after resolution of the symptomatic infection (occult HBV infection). In the present study we developed a highly sensitive method based on droplet digital PCR technology for the detection and quantitation of HBV cccDNA in the liver of individuals with occult HBV infection. We observed that the amount of HBV cccDNA may be inferred from the titer in serum of the IgG class antibody to the hepatitis B core antigen. The quantitation of this antibody may represent a surrogate to determine which patients are at the highest risk of HBV reactivation following immunosuppressive therapies.
Treatment of large bone defects represents a great challenge in orthopedic and craniomaxillofacial surgery. Although there are several methods for bone reconstruction, they all have specific ...indications and limitations. The concept of using barrier membranes for restoration of bone defects has been developed in an effort to simplify their treatment by offering a single-staged procedure. Research on this field of bone regeneration is ongoing, with evidence being mainly attained from preclinical studies. The purpose of this review is to summarize the current experimental and clinical evidence on the use of barrier membranes for restoration of bone defects in maxillofacial and orthopedic surgery. Although there are a few promising preliminary human studies, before clinical applications can be recommended, future research should aim to establish the 'ideal' barrier membrane and delineate the need for additional bone grafting materials aiming to 'mimic' or even accelerate the normal process of bone formation. Reproducible results and long-term observations with barrier membranes in animal studies, and particularly in large animal models, are required as well as well-designed clinical studies to evaluate their safety, efficacy and cost-effectiveness.
Objective
We aim to demonstrate that a chest X-ray (CXR) scoring system for COVID-19 patients correlates with patient outcome and has a prognostic value.
Methods
This retrospective study included ...CXRs of COVID-19 patients that reported the Brixia score, a semi-quantitative scoring system rating lung involvement from 0 to 18. The highest (H) and lowest (L) values were registered along with scores on admission (A) and end of hospitalization (E). The Brixia score was correlated with the outcome (death or discharge).
Results
A total of 953 patients met inclusion criteria. In total, 677/953 were discharged and 276/953 died during hospitalization. A total of 524/953 had one CXR and 429/953 had more than one CXR. H-score was significantly higher in deceased (median, 12; IQR 9–14) compared to that in discharged patients (median, 8; IQR 5–11) (
p
< 0.0001). In 429/953 patients with multiple CXR, A-score, L-score, and E-score were higher in deceased than in discharged patients (A-score 9 vs 8;
p
= 0.039; L-score 7 vs 5;
p
< 0.0003; E-score 12 vs 7;
p
< 0.0001). In the entire cohort, logistic regression showed a significant predictive value for age (
p
< 0.0001, OR 1.13), H-score (
p
< 0.0001, OR 1.25), and gender (
p
= 0.01, male OR 1.67). AUC was 0.863. In patients with ≥ 2 CXR, A-, L-, and E-scores correlated significantly with the outcome. Cox proportional hazards regression indicated age (
p
< 0.0001, HR 4.17), H-score (< 9, HR 0.36,
p
= 0.0012), and worsening of H-score vs A score > 3 (HR 1.57,
p
= 0.0227) as associated with worse outcome.
Conclusions
The Brixia score correlates strongly with disease severity and outcome; it may support the clinical decision-making, particularly in patients with moderate-to-severe signs and symptoms. The Brixia score should be incorporated in a prognostic model, which would be desirable, particularly in resource-constraint scenarios.
Key Points
• To demonstrate the importance of the Brixia score in assessing and monitoring COVID-19 lung involvement.
• The Brixia score strongly correlates with patient outcome and can be easily implemented in the routine reporting of CXR.
Production of nanotechnology-based materials is increasing worldwide: it is essential to evaluate their potential toxicity. Among these nanomaterials, carbon nanotubes (CNTs) have tremendous ...potential in many areas of research and applications. We have investigated the cyto- and genotoxic effects of single and multi-walled CNTs (SWCNTs, MWCNTs) and carbon black (CB) on the mouse macrophage cell line RAW 264.7. Specifically we have investigated inflammatory response, release of tumor necrosis factor-α (TNF-α), intracellular reactive oxygen species (ROS) production, cell death (both necrosis and apoptosis), chromosomal aberrations and cellular ultrastructural alteration caused by CB, MWCNTs and SWCNTs. Our data confirm that both CNTs and CB are cyto and geno-toxic to RAW 264.7 mouse macrophages. CNTs exposure induced ROS release, necrosis and chromosomal aberrations but did not cause an inflammatory response. In addition CNTs induce ultrastructural damage and apoptosis. CNTs penetrate the cell membrane and individual MWCNTs are seen associated with the nuclear envelope.
Patients with chronic hepatitis C (CHC) and concomitant type 2 diabetes mellitus (DM) show a higher risk of developing hepatocellular carcinoma (HCC). Successful antiviral therapy has reduced the ...incidence of post-therapy HCC, but the presence of DM still represents an unfavourable predictive factor even in cured patients. Metformin (MET) is recommended as a first-line therapy for DM, and its use is associated with a significant reduction in HCC among diabetic patients with chronic liver disease of different etiology, but very few studies specifically address this issue in patients with CHC.
the aim of this review is to evaluate whether the use of MET induces a significant decrease in HCC in diabetic patients with CHC, treated or untreated with antiviral therapy.
A search of PubMed, Medline, Web of Sciences and Embase was conducted for publications evaluating the role of MET in reducing the risk of HCC in patients with DM and CHC, with no language and study type restrictions up to 30 June 2023. Only studies fulfilling the following inclusion criteria were considered: (1) data on the incidence of HCC in the follow-up of diabetic patients with CHC only; (2) follow-up ≥24 months; (3) sufficient data to establish the rate of diabetic patients with CHC treated with metformin or other antidiabetic medications; and (4) data on the type of antiviral treatment and the clinical outcome.
Three studies met the inclusion criteria. A prospective cohort study considering only patients with DM and untreated advanced CHC, or non-responders to interferon (IFN) therapy, showed that the use of MET was associated with a significant decrease in HCC incidence, liver-related death and liver transplants. A recent retrospective study focusing on a large-scale nationwide cohort of patients with CHC in Taiwan successfully treated with IFN-based therapy stratified patients into 3 groups: non-MET users, MET users and non-diabetic patients, with 5-year cumulative rates of HCC of 10.9%, 2.6% and 3.0%, respectively, showing a significantly higher HCC risk in non-MET users compared with MET users and with non-diabetic patients, while it was not significantly different between MET users and non-diabetic patients. In a recent Italian cohort study focusing on 7007 patients with CHC treated and cured with direct-acting antiviral agents (DAAs), a combined effect of DM and MET therapy was found, showing a higher incidence of HCC in diabetic patients not taking MET compared with those without DM and those with DM taking MET.
according to the current evidence, the use of MET should be encouraged in diabetic patients with CHC in order to reduce the risk of HCC; however, a well-designed randomized controlled trial is needed to establish the generalizability of the beneficial effects of MET in this particular subset of patients.
Several studies on aeroterrestrial microalgae are unravelling their resistance mechanisms to different abiotic stressors, including hazardous metals, pointing to their future role as bioremediation ...microorganisms. In the present study, physiological and molecular alterations of four phycobionts of genus
Trebouxia (T.
TR1 and
T. TR9)
and
Coccomyxa
(
C. subellipsoidea
and
C. simplex
) exposed to Cd were studied. Cd accumulation and subcellular distribution, cell wall structure, production of biothiols (GSH and phytochelatins), reactive oxygen species (ROS) formation, expression of key antioxidant genes and ROS-related enzymes were evaluated to determine the physiological differences among the four microalgae, with the aim to identify the most suitable microorganism for further biotechnological applications. After 7 days of Cd exposure,
Coccomyxa
algae showed higher capacity of Cd intake than
Trebouxia
species, with
C. subellipsoidea
being the highest Cd accumulator at both intracellular and, especially, cell wall level. Cd induced ROS formation in the four microalgae, but to a greater extent in both
Coccomyxa
algae.
Trebouxia
TR9 showed the lowest Cd-dependent oxidative stress probably due to glutathione reductase induction. All microalgae synthetized phytochelatins in response to Cd but in a species-specific and a dose-dependent manner. Results from this study agree with the notion that each microalga has evolved a distinct strategy to detoxify hazardous metals like Cd and to cope with oxidative stress associated with them.
Coccomyxa subellipsoidea
and
Trebouxia
TR9 appear as the most interesting candidates for further applications.
As renewable energy sources are integrated into power systems, the complexity of their management increases. For the analysis of modern power systems, clustering algorithms have become indispensable ...tools. The representation of an electric power transmission system involves conceptualizing it as a graph-a mathematical structure depicting a set of nodes and edges. In the context of power systems, these nodes correspond to buses, and the edges represent branches. Weighting may be assigned to the edges to denote the strength of their connections. In this paper, spectral clustering and hierarchical agglomerative clustering have been employed to analyze the Italian transmission network. Spectral clustering relies on the eigenvalues and eigenvectors derived from the Laplacian matrix associated with the network. The hierarchical agglomerative clustering, based on Thévenin impedance to define the distances, merges the two closest clusters at each step. The primary objective of this research is to identify distinct areas within the network based solely on its topology. In pursuit of this goal, admittances and Thévenin impedances have been employed as weights in the graph representation. By utilizing these approaches, the research aims at uncovering meaningful structures and patterns within the power transmission system based on the inherent connectivity and strength of the network elements. The techniques have been used on two real network models to demonstrate the performance of the algorithms with different grid configurations.
Phenotypic dysmorphism is not rare to be found in the human oocyte, especially in the perivitelline space, which are among the most important aberration of the extra cytoplasmic component.
The case ...is of a 30-yr-old woman with no previous pregnancy, attempting an in vitro fertilization treatment for the first time. Given the extraordinary quantity of granular particles found in the perivitelline space, visible after the stripping procedure, it was not possible to establish the presence and position of the first polar body to appreciate the correct oocyte maturation (metaphase 2). Nevertheless, all the eggs were injected by the intracytoplasmic sperm injection. A time lapse incubator was used to perform the entire culture. Hence, a record of 6 days culture video was obtained. Only 2 eggs could fertilize correctly and reach the blastocyst stage on day 6. The embryos were frozen and subsequently transferred as frozen embryo transfer following the next menstrual cycle.
The exceptional presence of granular particles in the perivitelline space, which reminds us for aspects and behavior of the granulosa cells, seems to affect the fertilization but not the blastocysts quality. As a matter of fact, the woman, after the embryo transfer, achieved a successful twin live birth.
This study presents the assumptions and strategies for the practical implementation of the dynamic mode decomposition approach in the wide-area monitoring system of the Italian transmission system ...operator, Terna. The procedure setup aims to detect poorly damped interarea oscillations of power systems. Dynamic mode decomposition is a data-driven technique that has gained increasing attention in different fields; the proposed implementation can both characterize the oscillatory modes and identify the most influenced areas. This study presents the results of its practical implementation and operational experience in power system monitoring. It focuses on the main characteristics and solutions identified to reliably monitor the interarea electromechanical modes of the interconnected European power system. Moreover, conditions to issue an appropriate alarm in case of critical operating conditions are described. The effectiveness of the proposed approach is validated by its application in three case studies: a critical oscillatory event and a short-circuit event that occurred in the Italian power system in the previous years, and a 15-min time interval of normal grid operation recorded in March 2021.
Enzymes are essential components of biological reactions and play important roles in the scaling and optimization of many industrial processes. Due to the growing commercial demand for new and more ...efficient enzymes to help further optimize these processes, many studies are now focusing their attention on more renewable and environmentally sustainable sources for the production of these enzymes. Microalgae are very promising from this perspective since they can be cultivated in photobioreactors, allowing the production of high biomass levels in a cost-efficient manner. This is reflected in the increased number of publications in this area, especially in the use of microalgae as a source of novel enzymes. In particular, various microalgal enzymes with different industrial applications (e.g., lipids and biofuel production, healthcare, and bioremediation) have been studied to date, and the modification of enzymatic sequences involved in lipid and carotenoid production has resulted in promising results. However, the entire biosynthetic pathways/systems leading to synthesis of potentially important bioactive compounds have in many cases yet to be fully characterized (e.g., for the synthesis of polyketides). Nonetheless, with recent advances in microalgal genomics and transcriptomic approaches, it is becoming easier to identify sequences encoding targeted enzymes, increasing the likelihood of the identification, heterologous expression, and characterization of these enzymes of interest. This review provides an overview of the state of the art in marine and freshwater microalgal enzymes with potential biotechnological applications and provides future perspectives for this field.
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