Recent Advances on the Design and Applications of Antimicrobial Nanomaterials.

Present worldwide difficulties in healthcare and the environment have motivated the investigation and research of novel materials in an effort to find novel techniques to address the current challenges and requirements. In particular, the use of nanomaterials has demonstrated a significant promise in the fight against bacterial infections and the problem of antibiotic resistance. Metal nanoparticles and carbon-based nanomaterials in particular have been highlighted for their exceptional abilities to inhibit many types of bacteria and pathogens. In order for these materials to be as effective as possible, synthetic techniques are crucial. Therefore, in this review article, we highlight some recent developments in the design and synthesis of various nanomaterials, including metal nanoparticles (e.g., Ag, Zn, or Cu), metal hybrid nanomaterials, and the synthesis of multi-metallic hybrid nanostructured materials. Following that, examples of these materials' applications in antimicrobial performance targeted at eradicating multi-drug resistant bacteria, material protection such as microbiologically influenced corrosion (MIC), or additives in construction materials have been described.

Emergency department prediction model for 30-day mortality after hip fracture: the Spanish National Hip Fracture Registry (RNFC) cohort.

INTRODUCTION: The aim of this study was to design and validate a predictive model for 30-day mortality in a cohort of patients from the Spanish National Hip Fracture Registry (RNFC) with variables collected at the Emergency Department. METHODS: Retrospective study of a prospective database of hip fracture patients ⩾75 years old between 1 January 2017 and 30 September 2019. Patient characteristics, type of fracture and osteoprotective medication were collected at the Emergency Department. Univariate analysis compared the results between patients alive and deceased 30 days after hospital discharge. The variables associated with 30-day mortality in the regression analysis were age >85 years, male sex, indoors pre-fracture mobility, dementia, ASA score >3, pathological fracture, and vitamin D intake. A score scale was created with these variables. Discriminative performance was assessed using the area under the curve (AUC), calibration was assessed by applying Hosmer-Lemeshow goodness-of-fit test and predicted-to-observed mortality was compared. RESULTS: A total of 29,875 hip fracture cases were included in the study. The 30-day mortality of the overall cohort was 7.7%. A scale of 0-9 points was created, with a cut-off point of 4 points for the determination of patients at high risk of mortality. The AUC was 0.886. RNFC score presented good level of calibration (p = 0.139). The predicted-to-observed ratio was 1.09. CONCLUSIONS: The RNFC predictive model with variables collected at the Emergency Department showed an excellent predictive capacity for 30-day mortality in patients after hip fracture.

Design and Synthesis of Copper Nanobiomaterials with Antimicrobial Properties.

In this work, nanostructured copper materials have been designed, synthetized, and evaluated in order to produce a more efficient and sustainable copper bionanohybrid with catalytical and antimicrobial properties. Thus, conditions are sought where the most critical steps are reduced or minimized, such as the use of reducing agents or the cryogenization step. In addition, the new materials have been characterized through different techniques, and their oxidative and reductive capacities, as well as their antimicrobial activity, have been evaluated. The addition of different quantities of a reducing agent in the synthesis method generated copper bionanohybrids with different metallic species, nanoparticles sizes, and structures. The antimicrobial properties of the bionanohybrids were studied against different strains of Gram-positive and Gram-negative bacteria through two different methods: by counting the CFU and via the disk diffusion test, respectively. The bionanohybrids have demonstrated that different efficiencies depending on the bacterial strain were confronted with. The Cu-PHOS-100% R hybrids with the highest percentage of reduction showed the best antimicrobial efficiency against Escherichia coli and Klebsiella pneumoniae bacteria (>96 or >77% in 4 h, respectively) compared to 31% bacteria reduction using Cu-PHOS-0% R. Also, the antimicrobial activity against Bacillus subtilis materials was obtained with Cu-PHOS-100% R (31 mm inhibition zone and 125 µg/mL minimum inhibitory concentration value). Interestingly, the better antimicrobial activity of the nanobiohybrids against Gram-positive bacteria Mycobacterium smegmatis was obtained with some with a lower reduction step in the synthesis, Cu-PHOS-10% R or Cu-PHOS-20% R (>94% bacterial reduction in 4 h).

Female-specific enhancement of eosinophil recruitment and activation in a type 2 innate inflammation model in the lung.

A sex disparity in asthma prevalence and severity exists in humans. Multiple studies have highlighted the role for innate cells in shaping the adaptive immune system in chronic asthma. To explore the sex bias in the eosinophilic response, we delivered IL-33 to the lungs of mice and delineated the kinetics by which the inflammatory response was induced. Our data demonstrate that females recruited more eosinophils capable of responding to IL-33. Eosinophil activation occurred selectively in the lung tissue and was enhanced in females at all time points. This increase was associated with increased ex vivo type 2 cytokine and chemokine production and female-specific expansion of group 2 innate lymphoid cells lacking expression of the killer-cell lectin like receptor G1. Our findings suggest that the enhanced eosinophilic response in females is due, firstly, to a greater proportion of eosinophils recruited to the lungs in females that can respond to IL-33; and secondly, to an enhanced production of type 2 cytokines in females. Our data provide insight into the mechanisms that guide female-specific enhancement of eosinophil activation in the mouse and form the basis to characterize these responses in human asthmatics.

Copper(i) as a reducing agent for the synthesis of bimetallic PtCu catalytic nanoparticles.

This work investigates the potential utilization of Cu(i) as a reducing agent for the transformation of the platinum salt K2PtCl4, resulting in the production of stable nanoparticles. The synthesized nanoparticles exhibit a bimetallic composition, incorporating copper within their final structure. This approach offers a convenient and accessible methodology for the production of bimetallic nanostructures. The catalytic properties of these novel nanomaterials have been explored in various applications, including their use as artificial metalloenzymes and in the degradation of dyes. The findings underscore the significant potential of Cu(i)-mediated reduction in the development of functional nanomaterials with diverse catalytic applications.

Too Lucky to Be a Victim? An Exploratory Study of Online Harassment and Hate Messages Faced by Social Media Influencers.

Influencers are persistently exposed through social media. Once almost unapproachable, celebrities are now open to daily interaction with the public. From comments, polls, emails, and even private messages, the public can engage with their celebrities with a mere click. While this engagement provides influencers with advantages, it also renders them particularly susceptible to online harassment and toxic critics. This paper investigates the characteristics, impact, and reactions to cyber victimisation among social media influencers. To accomplish this objective, the paper presents the findings of two studies: a self-reported online victimisation survey conducted among Spanish influencers and an online ethnography. The results indicate that over 70% of influencers have encountered some form of online harassment and toxic critics. Cyber victimisation, its effects, and reactions vary across socio-demographic characteristics and the influencers' profiles. Furthermore, the qualitative analysis of the online ethnography reveals that harassed influencers can be classified as non-ideal victims. The implications of these findings for the literature are discussed.

Hiding in plain sight: Genome-wide recombination and a dynamic accessory genome drive diversity in Fusarium oxysporum f.sp. ciceris.

Understanding the origins of variation in agricultural pathogens is of fundamental interest and practical importance, especially for diseases that threaten food security. Fusarium oxysporum is among the most important of soil-borne pathogens, with a global distribution and an extensive host range. The pathogen is considered to be asexual, with horizontal transfer of chromosomes providing an analog of assortment by meiotic recombination. Here, we challenge those assumptions based on the results of population genomic analyses, describing the pathogen's diversity and inferring its origins and functional consequences in the context of a single, long-standing agricultural system. We identify simultaneously low nucleotide distance among strains, and unexpectedly high levels of genetic and genomic variability. We determine that these features arise from a combination of genome-scale recombination, best explained by widespread sexual reproduction, and presence-absence variation consistent with chromosomal rearrangement. Pangenome analyses document an accessory genome more than twice the size of the core genome, with contrasting evolutionary dynamics. The core genome is stable, with low diversity and high genetic differentiation across geographic space, while the accessory genome is paradoxically more diverse and unstable but with lower genetic differentiation and hallmarks of contemporary gene flow at local scales. We suggest a model in which episodic sexual reproduction generates haplotypes that are selected and then maintained through clone-like dynamics, followed by contemporary genomic rearrangements that reassort the accessory genome among sympatric strains. Taken together, these processes contribute unique genome content, including reassortment of virulence determinants that may explain observed variation in pathogenic potential.

BBB opening with focused ultrasound in nonhuman primates and Parkinson's disease patients: Targeted AAV vector delivery and PET imaging.

Intracerebral vector delivery in nonhuman primates has been a major challenge. We report successful blood-brain barrier opening and focal delivery of adeno-associated virus serotype 9 vectors into brain regions involved in Parkinson's disease using low-intensity focus ultrasound in adult macaque monkeys. Openings were well tolerated with generally no associated abnormal magnetic resonance imaging signals. Neuronal green fluorescent protein expression was observed specifically in regions with confirmed blood-brain barrier opening. Similar blood-brain barrier openings were safely demonstrated in three patients with Parkinson's disease. In these patients and in one monkey, blood-brain barrier opening was followed by 18F-Choline uptake in the putamen and midbrain regions based on positron emission tomography. This indicates focal and cellular binding of molecules that otherwise would not enter the brain parenchyma. The less-invasive nature of this methodology could facilitate focal viral vector delivery for gene therapy and might allow early and repeated interventions to treat neurodegenerative disorders.

Preparation of Highly Stable and Cost-Efficient Antiviral Materials for Reducing Infections and Avoiding the Transmission of Viruses such as SARS-CoV-2.

The current global pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has demonstrated the necessity to develop novel materials with antimicrobial and antiviral activities to prevent the infection. One significant route for the spread of diseases is by the transmission of the virus through contact with contaminated surfaces. Antiviral surface treatments can help to reduce or even avoid these hazards. In particular, the development of active-virucidal fabrics or paints represents a very important challenge with multiple applications in hospitals, public transports, or schools. Modern, cutting-edge methods for creating antiviral surface coatings use either materials with a metal base or sophisticated synthetic polymers. Even if these methods are effective, they will still face significant obstacles in terms of large-scale applicability. Here, we describe the preparation of fabrics and paints treated with a scaled-up novel nanostructured biohybrid material composed of very small crystalline phosphate copper(II) nanoparticles, synthesized based on a technology that employs the use of a small amount of biological agent for its formation at room temperature in aqueous media. We demonstrate the efficient inactivation of the human coronavirus 229E (HCoV-229E), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and non-enveloped human rhinovirus 14 (HRV-14) (>99.9%) using an inexpensive, ecologically friendly coating agent. The reactive oxygen species produced during the oxidation of water or the more intensive reaction with hydrogen peroxide are believed to be the cause of the antiviral mechanism of the nanostructured material. In contrast to the release of a specific antiviral drug, this process does not consume the surface coating and does not need regeneration. A 12-month aging research that revealed no decline in antiviral activity is proof that the coating is durable in ambient circumstances. Also, the coated fabric can be reused after different washing cycles, even at moderate to high temperatures.

Decoding the molecular heterogeneity of pediatric monomorphic post-solid organ transplant lymphoproliferative disorders.

Posttransplant lymphoproliferative disorders (PTLDs) represent a broad spectrum of lymphoid proliferations, frequently associated with Epstein-Barr virus (EBV) infection. The molecular profile of pediatric monomorphic PTLDs (mPTLDs) has not been elucidated, and it is unknown whether they display similar genetic features as their counterpart in adult and immunocompetent (IMC) pediatric patients. In this study, we investigated 31 cases of pediatric mPTLD after solid organ transplantation, including 24 diffuse large B-cell lymphomas (DLBCLs), mostly classified as activated B cell, and 7 cases of Burkitt lymphoma (BL), 93% of which were EBV positive. We performed an integrated molecular approach, including fluorescence in situ hybridization, targeted gene sequencing, and copy number (CN) arrays. Overall, PTLD-BL carried mutations in MYC, ID3, DDX3X, ARID1A, or CCND3 resembling IMC-BL, higher mutational burden than PTLD-DLBCL, and lesser CN alterations than IMC-BL. PTLD-DLBCL showed a very heterogeneous genomic profile with fewer mutations and CN alterations than IMC-DLBCL. Epigenetic modifiers and genes of the Notch pathway were the most recurrently mutated in PTLD-DLBCL (both 28%). Mutations in cell cycle and Notch pathways correlated with a worse outcome. All 7 patients with PTLD-BL were alive after treatment with pediatric B-cell non-Hodgkin lymphoma protocols, whereas 54% of patients with DLBCL were cured with immunosuppression reduction, rituximab, and/or low-dose chemotherapy. These findings highlight the low complexity of pediatric PTLD-DLBCL, their good response to low-intensity treatment, and the shared pathogenesis between PTLD-BL and EBV-positive IMC-BL. We also suggest new potential parameters that could help in the diagnosis and the design of better therapeutic strategies for these patients.

Meningitis por Listeria: serie de casos en un hospital de tercer nivel y utilidad de las nuevas técnicas de diagnóstico microbiológico

Introducción: La meningitis por Listeria monocytogenes (MLM) es una entidad grave con complicaciones a corto plazo. La reacción de polimerasa en cadena (RPC) puede ayudar a mejorar su diagnóstico y pronóstico. Objetivos: Conocer las características de los pacientes diagnosticados de meningitis por L. monocytogenes en los últimos años, a través de diferentes métodos microbiológicos. Pacientes y Métodos: Serie de casos de pacientes adultos ingresados con MLM en el Hospital Clínico San Carlos, Madrid, España, durante doce años (2009-2021). Se describieron variables epidemiológicas, clínicas, microbiológicas, radiológicas y terapéuticas. Resultados: Se registraron doce pacientes con MLM (edad media 67,5 años, 75% varones). En ocho se obtuvo un cultivo positivo a L. monocytogenes. La RPC en líquido cefalorraquídeo (LCR) fue positiva en los dos casos en los que se realizó la prueba. El tratamiento dirigido en todos los casos fue ampicilina durante 21 días. Se registraron complicaciones en un cuarto de los casos. Del total de pacientes uno falleció. Conclusiones: La MLM es una enfermedad poco frecuente y de difícil diagnóstico. En nuestra serie de casos los dos pacientes diagnosticados por RPC tuvieron resultado de cultivo de LCR negativo, y presentaron buena evolución. La determinación de RPC podría permitir diagnosticar un mayor número de casos y con mayor precocidad.

Background: Listeria monocytogenes meningitis (LMM) is a serious entity with short-term complications. Polymerase chain reaction (PCR) can help to improve its diagnosis and prognosis. Aim: To know the characteristics of patients diagnosed with meningitis by L. monocytogenes in recent years, through different microbiological methods. Methods: Case series of adult patients admitted with LMM at the Hospital Clínico San Carlos of Madrid, Spain, during twelve years (2009-2021). Epidemiological, clinical, microbiological, radiological and therapeutic variables were described. Results: Twelve patients with LMM were recorded (mean age 67.5 years, 75% male). Eight had a positive culture for L. monocytogenes. cerebrospinal fluid (CSF) PCR was positive in the two cases in which the test was performed. Treatment in all cases was ampicillin for 21 days. Complications were recorded in a quarter of the cases. One patient died. Conclusions: LMM is a rare and difficult to diagnose disease. In our series of cases, the two patients diagnosed by PCR had negative CSF culture results, and presented good evolution. PCR determination could allow a greater number of cases to be diagnosed earlier.

Chronic Treatment with Somatostatin Analogues in Recurrent Type 1 Gastric Neuroendocrine Tumors.

BACKGROUND: Type 1 gastric neuroendocrine tumors (GC-1) represent an uncommon subtype of neoplasms. Endoscopic resection has been proposed as the treatment of choice; active surveillance may be performed in those smaller than 1 cm, while gastric surgery may be performed for those with frequent recurrences. The antiproliferative effect of somatostatin analogues (SSA) is well known, and their action on GC-1s has been postulated as a chronic treatment to reduce recurrence. METHODS: A two-centered, retrospective, observational study that included nine patients (55.6% women) diagnosed with GC-1, receiving long-term treatment with SSA, with a median follow-up from baseline of 22 months, was undertaken. Endoscopic follow-up, extension study, and analytical values of chromogranin A (Cg A) and gastrin were collected. RESULTS: In total, 88.9% of patients presented partial or complete response. Treatment with SSA was the only independent factor with a trend to prevent tumor recurrence (Odds Ratio 0.054; p = 0.005). A nonsignificant tendency toward a decrease in CgA and gastrin was observed; lack of significance was probably related to concomitant treatment with proton pump inhibitors in some patients. CONCLUSIONS: Chronic treatment with SSA is a feasible option for recurrent GC-1s that are difficult to manage using endoscopy or gastrectomy. Randomized clinical trials to provide more scientific evidence are still needed.

Evaluation of the EUROIMMUN Aspergillus antigen immunoenzyme assay in serum and bronchoalveolar lavage fluid samples.

INTRODUCTION: The most widely used marker for the diagnosis of invasive aspergillosis (IA) is the detection of galactomannan by ELISA. This study describes the evaluation of the results obtained by Euroimmun Aspergillus antigen ELISA (EIA-GM-E) in serum samples and bronchoalveolar lavage fluid (BAL) from patients at risk of IA, and compares these results with those obtained by Bio-Rad Galactomannan EIA (EIA-GM-BR). METHODS: Anonymous retrospective case-control comparative study in 64 serum samples and 28 BAL from 51 patients. RESULTS: Overall agreement of the results of the two assays was observed in 72 of 92 samples (78.3%). The sensitivity of EIA-GM-BR and EIA-GM-E in serum samples was 88.9% and 43.2%, respectively, and 100% and 88.9% for BAL. The specificity of EIA-GM-BR and EIA-GM-E in serum samples was 91.9% for both assays, and 68.4% and 84.2% in BAL. There were no statistically significant differences in the results of both assays. CONCLUSIONS: Both methods show good results for the discrimination of patients with IA when BAL is tested, or serum in case of EIA-GM-BR.

Evaluation of the EUROIMMUN Aspergillus antigen immunoenzyme assay in serum and bronchoalveolar lavage fluid samples / Evaluación del EUROIMMUN Aspergillus antigen immunoenzyme assay en muestras de suero y lavado broncoalveolar

Introduction: The most widely used marker for the diagnosis of invasive aspergillosis (IA) is the detection of galactomannan by ELISA. This study describes the evaluation of the results obtained by Euroimmun Aspergillus antigen ELISA (EIA-GM-E) in serum samples and bronchoalveolar lavage fluid (BAL) from patients at risk of IA, and compares these results with those obtained by Bio-Rad Galactomannan EIA (EIA-GM-BR). Methods: Anonymous retrospective case–control comparative study in 64 serum samples and 28 BAL from 51 patients. Results: Overall agreement of the results of the two assays was observed in 72 of 92 samples (78.3%). The sensitivity of EIA-GM-BR and EIA-GM-E in serum samples was 88.9% and 43.2%, respectively, and 100% and 88.9% for BAL. The specificity of EIA-GM-BR and EIA-GM-E in serum samples was 91.9% for both assays, and 68.4% and 84.2% in BAL. There were no statistically significant differences in the results of both assays. Conclusions: Both methods show good results for the discrimination of patients with IA when BAL is tested, or serum in case of EIA-GM-BR.(AU)

Introducción: El marcador más utilizado para el diagnóstico de aspergilosis invasora (AI) es la detección de galactomanano mediante la técnica de ELISA. Este estudio describe la evaluación de los resultados obtenidos por Euroimmun Aspergillus antigen ELISA (EIA-GM-E) en muestras de suero y lavado broncoalveolar (LBA) de pacientes con factores de riesgo de AI, y compara sus resultados con los obtenidos por Bio-Rad Galactomannan EIA (EIA-GM-BR). Métodos: Estudio comparativo caso-control retrospectivo anónimo en 64 muestras de suero y 28 de LBA de 51 pacientes. Resultados: Se observó una concordancia global de resultados de los dos ensayos en 72 de las 92 muestras (78,3%). Los valores de sensibilidad de EIA-GM-BR y EIA-GM-E en suero fueron 88,9% y 43,2%, respectivamente, y para LBA 100% y 88,9%. La especificidad en suero de EIA-GM-BR y EIA-GM-E fue del 91,9% en ambos ensayos y para LBA 68,4% y 84,2%. No se observaron diferencias estadísticamente significativas en los resultados de ambos ensayos. Conclusiones: Ambos métodos demuestran buenos resultados para la discriminación de pacientes con AI cuando se emplea como muestra el LBA, o el suero en caso de EIA-GM-BR.(AU)

Temperature-induced formation of Pd nanoparticles in heterogeneous nanobiohybrids: application in C-H activation catalysis.

The effect of the temperature in the synthesis of Pd nanoparticles in the metal-enzyme biohybrids is evaluated. The effect on the formation, size, and morphology of nanoparticles was evaluated using C. antarctica B lipase as the protein scaffold. XRD analyses confirmed the formation of crystalline Pd(0) as the metal species in all cases. TEM analyses revealed spherical crystalline nanoparticles with average diameter size from 2 nm at 4 °C synthesis to 10 nm obtained at 50 °C synthesis. The thermal phenomenon was also critical in the final hybrid formation using more complex enzymes, where the relation of the protein structure and temperature and the influence of the latter has been demonstrated to be critical in the reducing efficiency of the enzyme in the final Pd nanoparticle formation, in the metal species, or even in the final size of the nanoparticles. Different Pd biohybrids were evaluated as catalysts in the C-H activation of protected l-tryptophan under mild conditions. Pd@CALB4 showed the best results, with >99% conversion for C-2 arylation in methanol at room temperature with a TOF value of 64 min-1, being 2 or 4 times higher than that of the other synthesized hybrids. This catalyst showed a very high stability and recyclability, maintaining >95% activity after three cycles of use.

Graphene-TLL-Cu2ONPs Hybrid as Highly Efficient Catalyst for Degradation of Organic Compounds.

In this work, Cu2O nanoparticles (NPs) were created in situ on graphene functionalized with Thermomyces lanuginosus lipase (G@TLL) where site-oriented supported TLL acted as template and binder in the presence of copper salt by tailorable synthesis under mild conditions, producing a heterogeneous catalyst. Cu2O NPs were confirmed by XRD and XPS. The TEM microscopy showed that the nanoparticles were homogeneously distributed over the G@TLL surface with sizes of 53 nm and 165 nm. This G@TLL-Cu2O hybrid was successfully used in the degradation of toxic organic compounds such as trichloroethylene (TCE) and Rhodamine B (RhB). In the case of TCE, the hybrid presented a high catalytic capacity, degrading 60 ppm of product in 60 min in aqueous solution and room temperature without the formation of other toxic subproducts. In addition, a TOF value of 7.5 times higher than the unsupported counterpart (TLL-Cu2O) was obtained, demonstrating the improved catalytic efficiency of the system in the solid phase. The hybrid also presented an excellent catalytic performance for the degradation of Rhodamine B (RhB) obtaining a complete degradation (48 ppm) in 50 min in aqueous solution and room temperature and with the presence of a green oxidant as H2O2.

Predicting the evolution of COVID-19 mortality risk: A Recurrent Neural Network approach.

Background: In December 2020, the COVID-19 disease was confirmed in 1,665,775 patients and caused 45,784 deaths in Spain. At that time, health decision support systems were identified as crucial against the pandemic. Methods: This study applies Deep Learning techniques for mortality prediction of COVID-19 patients. Two datasets with clinical information were used. They included 2,307 and 3,870 COVID-19 infected patients admitted to two Spanish hospitals. Firstly, we built a sequence of temporal events gathering all the clinical information for each patient, comparing different data representation methods. Next, we used the sequences to train a Recurrent Neural Network (RNN) model with an attention mechanism exploring interpretability. We conducted an extensive hyperparameter search and cross-validation. Finally, we ensembled the resulting RNNs to enhance sensitivity. Results: We assessed the performance of our models by averaging the performance across all the days in the sequences. Additionally, we evaluated day-by-day predictions starting from both the hospital admission day and the outcome day. We compared our models with two strong baselines, Support Vector Classifier and Random Forest, and in all cases our models were superior. Furthermore, we implemented an ensemble model that substantially increased the system's sensitivity while producing more stable predictions. Conclusions: We have shown the feasibility of our approach to predicting the clinical outcome of patients. The result is an RNN-based model that can support decision-making in healthcare systems aiming at interpretability. The system is robust enough to deal with real-world data and can overcome the problems derived from the sparsity and heterogeneity of data.

Neuroinflammation, immune response and α-synuclein pathology: how animal models are helping us to connect dots.

INTRODUCTION: A key pathological event occurring in Parkinson's disease (PD) is the transneuronal spreading of alpha-synuclein (α-syn). Other hallmarks of PD include neurodegeneration, glial activation, and immune cell infiltration in susceptible brain regions. Although preclinical models can mimic most of the key characteristics of PD, it is crucial to know the biological bases of individual differences between them when choosing one over another, to ensure proper interpretation of the results and to positively influence the outcome of the experiments. AREAS COVERED: This review provides an overview of current preclinical models actively used to study the interplay between α-syn pathology, neuroinflammation and immune response in PD but also to explore new potential preclinical models or emerging therapeutic strategies intended to fulfill the unmet medical needs in this disease. Lastly, this review also considers the current state of the ongoing clinical trials of new drugs designed to target these processes and delay the initiation or progression of the disease. EXPERT OPINION: Anti-inflammatory and immunomodulatory agents have been demonstrated to be very promising candidates for reducing disease progression; however, more efforts are needed to reduce the enormous gap between these and dopaminergic drugs, which have dominated the therapeutic market for the last sixty years.

An Evaluation of Serological Tests to Determine Postvaccinal Immunity to SARS-CoV-2 by mRNA Vaccines.

BACKGROUND: The duration of the protective efficacy of vaccines against SARS-CoV-2 is unknown. Thus, an evaluation of the clinical performance of available tests is required. OBJECTIVES: To evaluate the clinical performance of LFIA immunoassay compared to ELIA and CLIA immunoassays available in Europe for the detection of IgG antibodies generated by mRNA vaccines against SARS-CoV-2. METHODS: Two automated immunoassays (the EUROIMMUN anti-SARS-CoV-2 IgG S1 ELISA and the LIAISON de Diasorin anti-SARS-CoV-2 IgG S1/S2 test) and a lateral flow immunoassay (the Livzon LFIA anti-SARS-CoV-2 IgG S test) were tested. We analyzed 300 samples distributed in three groups: 100 subjects aged over 18 years and under 45 years, 100 subjects aged between 45 and 65 years, and 100 subjects aged over 65 years. The samples were collected before vaccination; at 21 days; and then at 1, 2, 3, and 6 months after vaccination. The sensitivity, specificity, positive predictive value, negative predictive value, positive probability quotient, negative probability quotient, and concordance (kappa index) were calculated for each serological test. RESULTS: The maximum sensitivity values for IgG were 98.7%, 98.1%, and 97.8% for the EUROIMMUN ELISA, Abbott CLIA, and Livzon LFIA tests, respectively, and the maximum specificity values for IgG were 99.4%, 99.9%%, and 98.4% for the ELISA, CLIA, and LFIA tests, respectively, at the third month after vaccination, representing a decrease in the antibody levels after the sixth month. The best agreement was observed between the ELISA and CLIA tests at 100% (k = 1.00). The agreement between the ELIA, CLIA, and LFIA tests was 99% (k = 0.964) at the second and third month after vaccination. Seroconversion was faster and more durable in the younger age groups. CONCLUSION: Our study examined the equivalent and homogeneous clinical performance for IgG of three immunoassays after vaccination and found LFIA to be the most cost-effective, reliable, and accurate for routine use in population seroconversion and seroprevalence studies.

Cascade Catalysis Through Bifunctional Lipase Metal Biohybrids for the Synthesis of Enantioenriched O-Heterocycles from Allenes.

Lipase/metal nanobiohybrids, generated by growth of silver or gold nanoparticles on protein matrixes are used as highly effective dual-activity heterogeneous catalysts for the production of enantiomerically enriched 2,5-dihydrofurans from allenic acetates in a one-pot cascade process combining a lipase-mediated hydrolytic kinetic resolution with a metal-catalyzed allene cycloisomerization. Incorporating a novel strategy based on enzyme-polymer bioconjugates in the nanobiohybrid preparation enables excellent conversions in the process. Candida antarctica lipase B (CALB) in combination with a dextran-based polymer modifier (DexAsp) proved to be most efficient when merged with silver nanoparticles. A range of hybrid materials were produced, combining Ag or Au metals with Thermomyces lanuginosus lipase (TLL) or CALB and its DexAsp or polyethyleneimine polymer bioconjugates. The wider applicability of the biohybrids is demonstrated by their use in allenic alcohol cyclizations, where a variety of dihydrofurans are obtained using a CALB/gold nanomaterial. These results underline the potential of the nanobiohybrid catalysis as promising approach to intricate one-pot synthetic strategies.