Kinetics and persistence of cellular and humoral immune responses to SARS-CoV-2 vaccine in healthcare workers with or without prior COVID-19.

SARS-CoV-2 vaccines are highly efficient against severe forms of the disease, hospitalization and death. Nevertheless, insufficient protection against several circulating viral variants might suggest waning immunity and the need for an additional vaccine dose. We conducted a longitudinal study on the kinetics and persistence of immune responses in healthcare workers vaccinated with two doses of BNT162b2 mRNA vaccine with or without prior SARS-CoV-2 infection. No new infections were diagnosed during follow-up. At 6 months, post-vaccination or post-infection, despite a downward trend in the level of anti-S IgG antibodies, the neutralizing activity does not decrease significantly, remaining higher than 75% (85.14% for subjects with natural infection, 88.82% for vaccinated after prior infection and 78.37% for vaccinated only). In a live-virus neutralization assay, the highest neutralization titres were present at baseline and at 6 months follow-up in persons vaccinated after prior infection. Anti-S IgA levels showed a significant descending trend in vaccinated subjects (p < 0.05) after 14 weeks. Cellular immune responses are present even in vaccinated participants with declining antibody levels (index ratio 1.1-3) or low neutralizing activity (30%-40%) at 6 months, although with lower T-cell stimulation index (p = 0.046) and IFN-γ secretion (p = 0.0007) compared to those with preserved humoral responses.

Disruption of a miR-29 binding site leading to COL4A1 upregulation causes pontine autosomal dominant microangiopathy with leukoencephalopathy.

OBJECTIVE: Cerebral small vessel disease (cSVD) is a heterogeneous group of disorders. Screening of known cSVD genes identifies the causative mutation in <15% of familial cSVD cases. We sought to identify novel causes of cSVD. METHODS: We used linkage analysis and exome sequencing to identify the causal mutation in a French cSVD family. The identified candidate gene was then screened in 202 cSVD unrelated probands, including 1 proband from the first reported pontine autosomal dominant microangiopathy with leukoencephalopathy (PADMAL) family. Sanger sequencing was used to confirm variants in all mutated probands and analyze their segregation in probands' relatives. Mutation consequences were assessed with luciferase reporter assays and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: A candidate heterozygous variant located in a predicted miR-29 microRNA binding site, within the 3' untranslated region of COL4A1, was identified in the large French cSVD family. Five additional unrelated probands, including the PADMAL proband, harbored heterozygous variants in this microRNA binding site. Variants cosegregated with the affected phenotype, and cumulative logarithm of odds score reached 6.03, establishing linkage to this locus. A highly significant difference was observed when comparing the number of variants within this binding site in cases and controls (p = 1.77 × 10E-12). RT-qPCR analyses of patients' primary fibroblasts and luciferase reporter assays strongly favor an upregulation of COL4A1 mediated by disruption of miR-29 binding to its target site. Magnetic resonance imaging features were characterized by the presence of multiple pontine infarcts in all symptomatic mutation carriers. INTERPRETATION: Mutations upregulating COL4A1 expression lead to PADMAL, a severe early onset ischemic cSVD, distinct from the various phenotypes associated with COL4A1 missense glycine mutations. Ann Neurol 2016;80:741-753.

Retained Common Bile Duct Lithiasis at a Pacient with Periampullary Duodenal Diverticulum.

Periampullary duodenal diverticula are associated with the presence of common bile duct stones, being encountered more frequently with the increase of age. We present the case of a 76 years old female patient, who underwents emergency surgery for a perforated lithiasic gangrenous acute cholecystitis and for whom we perform a cholecystectomy and an external biliary drainage using a transcystic tube. Both preoperative and postoperative imaging and endoscopic examinations certify the presence of a periampullary duodenal diverticulum. Postoperative cholangiography performed on the transcystic tube raises the suspicion of retained common bile duct lithiasis. An endoscopic retrograde cholangiopancreatography is performed, initially failing to cannulate the common bile duct. A precut sphincterotomy fistula technnique is performed, using as reference a guide inserted on the transcystic tube, with the extraction of biliay sludge from the common bile duct, and with subsequently favorable development. Association between common bile duct lithiasis and a periampullary duodenal diverticulum may represent a therapeutic challenge because of the increased risk of failure of the endoscopic treatment.

Exploring Key Barriers of HACCP Certification Adoption in the Meat Industry: A Decision-Making Trial and Evaluation Laboratory Approach.

Food safety management represents an important concern in contemporary society. The Hazard Analysis Critical Control Point (HACCP) system is a crucial tool for meat producers, preventing and controlling major food safety concerns in the process. This research investigates key barriers to HACCP implementation in the meat industry, employing the Decision-Making Trial and Evaluation Laboratory (DEMATEL) model to identify and categorize these obstacles. Using the insights of 18 experts, a cause-and-effect relationship diagram is generated through which twelve barriers are categorized in terms of their cause and effect and then analyzed. Threshold value is calculated as 0.299. The findings reveal poor management as the primary impediment, followed by challenges in training, knowledge, and dedication. Categorizing the barriers into four groups emphasizes the critical role of effective management and human resources. The study contributes valuable insights to food safety management literature, serving as a practical resource for industry practitioners. Despite limitations in relying on expert opinions and the industry-specific focus, the research lays a foundation for informed decision-making, stressing the importance of effective management in successful HACCP implementation. Future research directions include diversifying geographical representation, exploring practical solutions, and integrating emerging technologies for a better understanding of HACCP adoption challenges.

Key considerations for pathogen surveillance in wastewater.

Wastewater surveillance (WWS) has received significant attention as a rapid, sensitive, and cost-effective tool for monitoring various pathogens in a community. WWS is employed to assess the spatial and temporal trends of diseases and identify their early appearances and reappearances, as well as to detect novel and mutated variants. However, the shedding rates of pathogens vary significantly depending on factors such as disease severity, the physiology of affected individuals, and the characteristics of pathogen. Furthermore, pathogens may exhibit differential fate and decay kinetics in the sewerage system. Variable shedding rates and decay kinetics may affect the detection of pathogens in wastewater. This may influence the interpretation of results and the conclusions of WWS studies. When selecting a pathogen for WWS, it is essential to consider it's specific characteristics. If data are not readily available, factors such as fate, decay, and shedding rates should be assessed before conducting surveillance. Alternatively, these factors can be compared to those of similar pathogens for which such data are available.

Environmental microbiome diversity and stability is a barrier to antimicrobial resistance gene accumulation.

When antimicrobial resistant bacteria (ARB) and genes (ARGs) reach novel habitats, they can become part of the habitat's microbiome in the long term if they are able to overcome the habitat's biotic resilience towards immigration. This process should become more difficult with increasing biodiversity, as exploitable niches in a given habitat are reduced for immigrants when more diverse competitors are present. Consequently, microbial diversity could provide a natural barrier towards antimicrobial resistance by reducing the persistence time of immigrating ARB and ARG. To test this hypothesis, a pan-European sampling campaign was performed for structured forest soil and dynamic riverbed environments of low anthropogenic impact. In soils, higher diversity, evenness and richness were significantly negatively correlated with relative abundance of >85% of ARGs. Furthermore, the number of detected ARGs per sample were inversely correlated with diversity. However, no such effects were present in the more dynamic riverbeds. Hence, microbiome diversity can serve as a barrier towards antimicrobial resistance dissemination in stationary, structured environments, where long-term, diversity-based resilience against immigration can evolve.

Making waves: The NORMAN antibiotic resistant bacteria and resistance genes database (NORMAN ARB&ARG)-An invitation for collaboration to tackle antibiotic resistance.

With the global concerns on antibiotic resistance (AR) as a public health issue, it is pivotal to have data exchange platforms for studies on antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in the environment. For this purpose, the NORMAN Association is hosting the NORMAN ARB&ARG database, which was developed within the European project ANSWER. The present article provides an overview on the database functionalities, the extraction and the contribution of data to the database. In this study, AR data from three studies from China and Nepal were extracted and imported into the NORMAN ARB&ARG in addition to the existing AR data from 11 studies (mainly European studies) on the database. This feasibility study demonstrates how the scientific community can share their data on AR to generate an international evidence base to inform AR mitigation strategies. The open and FAIR data are of high potential relevance for regulatory applications, including the development of emission limit values / environmental quality standards in relation to AR. The growth in sharing of data and analytical methods will foster collaboration on risk management of AR worldwide, and facilitate the harmonization in the effort for identification and surveillance of critical hotspots of AR. The NORMAN ARB&ARG database is publicly available at: https://www.norman-network.com/nds/bacteria/.

Polymeric Membranes for Biomedical Applications.

Polymeric membranes are selective materials used in a wide range of applications that require separation processes, from water filtration and purification to industrial separations. Because of these materials' remarkable properties, namely, selectivity, membranes are also used in a wide range of biomedical applications that require separations. Considering the fact that most organs (apart from the heart and brain) have separation processes associated with the physiological function (kidneys, lungs, intestines, stomach, etc.), technological solutions have been developed to replace the function of these organs with the help of polymer membranes. This review presents the main biomedical applications of polymer membranes, such as hemodialysis (for chronic kidney disease), membrane-based artificial oxygenators (for artificial lung), artificial liver, artificial pancreas, and membranes for osseointegration and drug delivery systems based on membranes.

Preparation and Characterization of Chitosan/LDH Composite Membranes for Drug Delivery Application.

In this study, composite membranes based on chitosan (CS), layered double hydroxide (LDH), and diclofenac were prepared via dispersing of LDH and diclofenac (DCF) in the chitosan matrix for gradual delivery of diclofenac sodium. The effect of using LDH in composites was compared to chitosan loaded with diclofenac membrane. LDH was added in order to develop a system with a long release of diclofenac sodium, which is used in inflammatory conditions as an anti-inflammatory drug. The prepared composite membranes were characterized by Fourier Transform Infrared Spectroscopy (FT-IR), Scanning Electron Microscope Analysis (SEM), X-ray Photoelectron Spectroscopy (XPS), Thermogravimetric Analysis (TGA) and UV-Vis Spectroscopy. The results of the FTIR and XPS analyses confirmed the obtaining of the composite membrane and the efficient incorporation of diclofenac. It was observed that the addition of LDH can increase the thermal stability of the composite membrane and favors the gradual release of diclofenac, highlighted by UV-Vis spectra that showed a gradual release in the first 48 h. In conclusion, the composite membrane based on CS-LDH can be used in potential drug delivery application.

Global trends and research hotspots on HACCP and modern quality management systems in the food industry.

HACCP (Hazard Analysis and Critical Control Points) and modern quality management systems have a significant impact on public health in the food industry. These systems ensure that food products are safe for consumption by identifying and managing potential hazards at every stage of the production process. To stimulate ongoing studies in both developing and underexplored areas of inquiry, this research synthesizes and organizes the contributions made in this field. It examines more than 40 years of studies from Scopus data base on HACCP and modern quality management systems in the food industry using the VOSviewer software version 1.6.18 (Leiden University, The Netherlands) and bibliometrix R-package. This represents, to the authors' knowledge, the first bibliometric analysis undergone in this direction. The graphical framework demonstrates the highest developments in research and the literature review investigates barriers and opportunities of implementing HACCP in food industry organizations. Findings indicate that until the beginning of the 1990s, there was not a large number of scientific production in the field of HACCP and modern quality management systems in the food industry. The USA were the most prolific affiliation terms of scientific production until 2012, when studies from Italy, the United Kingdom, China and Greece intensified. Currently, the most prolific country in terms of publications is Italy. In terms of global cooperation, the United Kingdom, The United States and The Netherlands represent most active nations on this topic Motor themes that reflect the main interest of the researchers include food diseases, quality control, hazards or food supply. The study also provides future research directions regarding food quality and safety management. These should be focused on improving the safety, quality, and sustainability of food products, while also adapting to changing consumer demands, emerging risks, and regulatory requirements.

Functionalized Hemodialysis Polysulfone Membranes with Improved Hemocompatibility.

The field of membrane materials is one of the most dynamic due to the continuously changing requirements regarding the selectivity and the upgradation of the materials developed with the constantly changing needs. Two membrane processes are essential at present, not for development, but for everyday life-desalination and hemodialysis. Hemodialysis has preserved life and increased life expectancy over the past 60-70 years for tens of millions of people with chronic kidney dysfunction. In addition to the challenges related to the efficiency and separative properties of the membranes, the biggest challenge remained and still remains the assurance of hemocompatibility-not affecting the blood during its recirculation outside the body for 4 h once every two days. This review presents the latest research carried out in the field of functionalization of polysulfone membranes (the most used polymer in the preparation of membranes for hemodialysis) with the purpose of increasing the hemocompatibility and efficiency of the separation process itself with a decreasing impact on the body.

Recent Advances in Stimuli-Responsive Doxorubicin Delivery Systems for Liver Cancer Therapy.

Doxorubicin (DOX) is one of the most commonly used drugs in liver cancer. Unfortunately, the traditional chemotherapy with DOX presents many limitations, such as a systematic release of DOX, affecting both tumor tissue and healthy tissue, leading to the apparition of many side effects, multidrug resistance (MDR), and poor water solubility. Furthermore, drug delivery systems' responsiveness has been intensively studied according to the influence of different internal and external stimuli on the efficiency of therapeutic drugs. In this review, we discuss both internal stimuli-responsive drug-delivery systems, such as redox, pH and temperature variation, and external stimuli-responsive drug-delivery systems, such as the application of magnetic, photo-thermal, and electrical stimuli, for the controlled release of Doxorubicin in liver cancer therapy, along with the future perspectives of these smart delivery systems in liver cancer therapy.

Emergence of SARS-CoV-2 Alpha lineage and its correlation with quantitative wastewater-based epidemiology data.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gave rise to an international public health emergency in 3 months after its emergence in Wuhan, China. Typically for an RNA virus, random mutations occur constantly leading to new lineages, incidental with a higher transmissibility. The highly infective alpha lineage, firstly discovered in the UK, led to elevated mortality and morbidity rates as a consequence of Covid-19, worldwide. Wastewater surveillance proved to be a powerful tool for early detection and subsequent monitoring of the dynamics of SARS-CoV-2 and its variants in a defined catchment. Using a combination of sequencing and RT-qPCR approaches, we investigated the total SARS-CoV-2 concentration and the emergence of the alpha lineage in wastewater samples in Vienna, Austria linking it to clinical data. Based on a non-linear regression model and occurrence of signature mutations, we conclude that the alpha variant was present in Vienna sewage samples already in December 2020, even one month before the first clinical case was officially confirmed and reported by the health authorities. This provides evidence that a well-designed wastewater monitoring approach can provide a fast snapshot and may detect the circulating lineages in wastewater weeks before they are detectable in the clinical samples. Furthermore, declining 14 days prevalence data with simultaneously increasing SARS-CoV-2 total concentration in wastewater indicate a different shedding behavior for the alpha variant. Overall, our results support wastewater surveillance to be a suitable approach to spot early circulating SARS-CoV-2 lineages based on whole genome sequencing and signature mutations analysis.

Sponges from Plasma Treated Cellulose Nanofibers Grafted with Poly(ethylene glycol)methyl Ether Methacrylate.

In this work, cellulose nanofibers (CNF) were surface treated by plasma and grafted with poly(ethylene glycol)methyl ether methacrylate (PEGMMA) for increasing mechanical strength and hydrophobicity. The surface characteristics of the sponges were studied by scanning electron microscopy, micro-computed tomography, and Fourier transform infrared spectroscopy, which demonstrated successful surface modification. Plasma treatment applied to CNF suspension led to advanced defibrillation, and the resulting sponges (CNFpl) exhibited smaller wall thickness than CNF. The grafting of PEGMMA led to an increase in the wall thickness of the sponges and the number of larger pores when compared with the non-grafted counterparts. Sponges with increased hydrophobicity demonstrated by an almost 4 times increase in the water contact angle and better mechanical strength proved by 2.5 times increase in specific compression strength were obtained after PEGMMA grafting of plasma treated CNF. Cells cultivated on both neat and PEGMMA-grafted CNF sponges showed high viability (>99%). Remarkably, CNF grafted with PEGMMA showed better cell viability as compared with the untreated CNF sample; this difference is statistically significant (p < 0.05). In addition, the obtained sponges do not trigger an inflammatory response in macrophages, with TNF-α secretion by cells in contact with CNFpl, CNF-PEGMMA, and CNFpl-PEGMMA samples being lower than that observed for the CNF sample. All these results support the great potential of cellulose nanofibers surface treated by plasma and grafted with PEGMMA for biomedical applications.

Mesoporous Silica Materials Loaded with Gallic Acid with Antimicrobial Potential.

This paper aimed to develop two types of support materials with a mesoporous structure of mobile crystalline matter (known in the literature as MCM, namely MCM-41 and MCM-48) and to load them with gallic acid. Soft templating methodology was chosen for the preparation of the mesoporous structures-the cylindrical micelles with certain structural characteristics being formed due to the hydrophilic and hydrophobic intermolecular forces which occur between the molecules of the surfactants (cetyltrimethylammonium bromide-CTAB) when a minimal micellar ionic concentration is reached. These mesoporous supports were loaded with gallic acid using three different types of MCM-gallic acid ratios (1:0.41; 1:0.82 and 1:1.21)-and their characterizations by FTIR, SEM, XRD, BET and drug release were performed. It is worth mentioning that the loading was carried out using a vacuum-assisted methodology: the mesoporous materials are firstly kept under vacuum at ~0.1 barr for 30 min followed by the addition of the polyphenol solutions. The concentration of the solutions was adapted such that the final volume covered the wet mesoporous support and-in this case-upon reaching normal atmospheric pressure, the solution was pushed inside the pores, and thus the polyphenols were mainly loaded inside the pores. Based on the SBET data, it can be seen that the specific surface area decreased considerably with the increasing ratio of gallic acid; the specific surface area decreased 3.07 and 4.25 times for MCM-41 and MCM-48, respectively. The sample with the highest polyphenol content was further evaluated from a biological point of view, alone or in association with amoxicillin administration. As expected, the MCM-41 and MCM-48 were not protective against infections-but, due to the loading of the gallic acid, a potentiated inhibition was recorded for the tested gram-negative bacterial strains. Moreover, it is important to mention that these systems can be efficient solutions for the recovery of the gut microbiota after exposure to antibiotics, for instance.

Viral variant-resolved wastewater surveillance of SARS-CoV-2 at national scale.

SARS-CoV-2 surveillance by wastewater-based epidemiology is poised to provide a complementary approach to sequencing individual cases. However, robust quantification of variants and de novo detection of emerging variants remains challenging for existing strategies. We deep sequenced 3,413 wastewater samples representing 94 municipal catchments, covering >59% of the population of Austria, from December 2020 to February 2022. Our system of variant quantification in sewage pipeline designed for robustness (termed VaQuERo) enabled us to deduce the spatiotemporal abundance of predefined variants from complex wastewater samples. These results were validated against epidemiological records of >311,000 individual cases. Furthermore, we describe elevated viral genetic diversity during the Delta variant period, provide a framework to predict emerging variants and measure the reproductive advantage of variants of concern by calculating variant-specific reproduction numbers from wastewater. Together, this study demonstrates the power of national-scale WBE to support public health and promises particular value for countries without extensive individual monitoring.

Properties of Polysiloxane/Nanosilica Nanodielectrics for Wearable Electronic Devices.

Polymer nanodielectrics characterized by good flexibility, processability, low dielectric loss and high dielectric permittivity are materials of interest for wearable electronic devices and intelligent textiles, and are highly in demand in robotics. In this study, an easily scalable and environmentally friendly method was applied to obtain polysiloxane/nanosilica nanocomposites with a large content of nanofiller, of up to 30% by weight. Nanosilica was dispersed both as individual particles and as agglomerates; in nanocomposites with a lower amount of filler, the former prevailed, and at over 20 wt% nanosilica the agglomerates predominated. An improvement of both the tensile strength and modulus was observed for nanocomposites with 5-15 wt% nanosilica, and a strong increase of the storage modulus was observed with the increase of nanofiller concentration. Furthermore, an increase of the storage modulus of up to seven times was observed in the nanocomposites with 30 wt% nanosilica. The tensile modulus was well fitted by models that consider the aggregation of nanoparticles and the role of the interface. The dielectric spectra showed an increase of the real part of the complex relative permittivity with 33% for 30 wt% nanosilica in nanocomposites at a frequency of 1 KHz, whereas the loss tangent values were lower than 0.02 for all tested nanodielectrics in the radio frequency range between 1 KHz and 1 MHz. The polysiloxane-nanosilica nanocomposites developed in this work showed good flexibility; however, they also showed increased stiffness along with a stronger dielectric response than the unfilled polysiloxane, which recommends them as dielectric substrates for wearable electronic devices.

Resilience of agricultural soils to antibiotic resistance genes introduced by agricultural management practices.

Antimicrobial resistance (AR) represents a global threat in human and veterinary medicine. In that regard, AR proliferation and dissemination in agricultural soils after manure application raises concerns on the enrichment of endogenous soil bacterial population with allochthonous antibiotic resistance genes (ARGs). Natural resilience of agricultural soils and background concentrations of ARGs play key roles in the mitigation of AR propagation in natural environments. In the present study, we carried out a longitudinal sampling campaign for two crop vegetation periods to monitor spatial and temporal changes in the abundance of seven clinically relevant ARGs (sul1, ermB, vanA, aph(3')-IIa, aph(3')-IIIa, blaTEM-1 and tet(W)) and ribosomal 16S RNA. The absolute and relative abundances of the selected ARGs were quantified in total community DNA extracted from agricultural (manured and non-manured) and forest soils, fresh pig faeces and manure slurry. We observed that ARG concentrations return to background levels after manure-induced exposure within a crop growing season, highlighting the resilience capacity of soil. Naturally occurring high background concentrations of ARGs can be found in forest soil in due distance under low anthropogenic influences. It was observed that pesticide application increases the concentrations of three out of seven ARGs tested (ermB, aph(3')-IIIa and tet(W)). Moreover, we noticed that the absolute abundances of sul1, vanA, ermB and blaTEM-1 resistance genes show an increase by 100- to 10,000- fold, from maturation of fresh pig faeces to manure. Outcomes of our study suggest that agricultural soil environments show a strong capacity to alleviate externally induced disturbances in endogenous ARG concentrations. Naturally occurring high concentrations of ARGs are present also in low human impacted environments represented by the indigenous resistome.

Influence of TEMPO oxidation on the properties of ethylene glycol methyl ether acrylate grafted cellulose sponges.

In this study, cellulose nanofibers (CNF) obtained via high-pressure microfluidization were 2,6,6-tetra-methylpiperidine-1-oxyl (TEMPO) oxidized (TOCNF) in order to facilitate the grafting of ethylene glycol methyl ether acrylate (EGA). FTIR and XPS analyses revealed a more efficient grafting of EGA oligomers on the surface of TOCNF as compared to the original CNF. As a result, a consistent covering of the TOCNF fibers with EGA oligomers, an increased hydrophobicity and a reduction in porosity were noticed for TOCNF-EGA. However, the swelling ratio of TOCNF-EGA was similar to that of original CNF grafted with EGA and higher than that of TOCNF, because the higher amount of grafted EGA onto oxidized cellulose and the looser structure reduced the contacts between the fibrils and increased the absorption of water. All these results corroborated with a good cytocompatibility and compression strength recommend TOCNF-EGA for applications in regenerative medicine.

Low Molecular Weight and Polymeric Modifiers as Toughening Agents in Poly(3-Hydroxybutyrate) Films.

The inherent brittleness of poly(3-hydroxybutyrate) (PHB) prevents its use as a substitute of petroleum-based polymers. Low molecular weight plasticizers, such as tributyl 2-acetyl citrate (TAC), cannot properly solve this issue. Herein, PHB films were obtained using a biosynthesized poly(3-hydroxyoctanoate) (PHO) and a commercially available TAC as toughening agents. The use of TAC strongly decreased the PHB thermal stability up to 200 °C due to the loss of low boiling point plasticizer, while minor weight loss was noticed at this temperature for the PHB-PHO blend. Both agents shifted the glass transition temperature of PHB to a lower temperature, the effect being more pronounced for TAC. The elongation at break of PHB increased by 700% after PHO addition and by only 185% in the case of TAC; this demonstrates an important toughening effect of the polymeric modifier. Migration of TAC to the upper surface of the films and no sign of migration in the case of PHO were highlighted by X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) results. In vitro biocompatibility tests showed that all the PHB films are non-toxic towards L929 cells and have no proinflammatory immune response. The use of PHO as a toughening agent in PHB represents an attractive solution to its brittleness in the case of packaging and biomedical applications while conserving its biodegradability and biocompatibility.