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The growing interest in the role of microglia in the progression of many neurodegenerative diseases is developing in an ever-expedited manner, in part thanks to emergent new tools for studying the morphological and functional features of the CNS. The discovery of specific biomarkers of the microglia phenotype could find application in a wide range of human diseases, and creates opportunities for the discovery and development of tailored therapeutic interventions. Among these, recent studies highlight the pivotal role of the potassium channels in regulating microglial functions in physiological and pathological conditions such as Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis. In this review, we summarize the current knowledge of the involvement of the microglial potassium channels in several neurodegenerative diseases and their role as modulators of microglial homeostasis and dysfunction in CNS disorders.

Duchenne muscular dystrophy (DMD) is an X-linked disease, caused by a mutant dystrophin gene, leading to muscle membrane instability, followed by muscle inflammation, infiltration of pro-inflammatory macrophages and fibrosis. The calcium-activated potassium channel type 3.1 (KCa3.1) plays key roles in controlling both macrophage phenotype and fibroblast proliferation, two critical contributors to muscle damage. In this work, we demonstrate that pharmacological blockade of the channel in the mdx mouse model during the early degenerative phase favors the acquisition of an anti-inflammatory phenotype by tissue macrophages and reduces collagen deposition in muscles, with a concomitant reduction of muscle damage. As already observed with other treatments, no improvement in muscle performance was observed in vivo. In conclusion, this work supports the idea that KCa3.1 channels play a contributing role in controlling damage-causing cells in DMD. A more complete understanding of their function could lead to the identification of novel therapeutic approaches.

Duchenne muscular dystrophy (DMD) is an X-linked disease, caused by a mutant dystrophin gene, leading to muscle membrane instability, followed by muscle inflammation, infiltration of pro-inflammatory macrophages and fibrosis. The calcium-activated potassium channel type 3.1 (K 3.1) plays key roles in controlling both macrophage phenotype and fibroblast proliferation, two critical contributors to muscle damage. In this work, we demonstrate that pharmacological blockade of the channel in the mouse model during the early degenerative phase favors the acquisition of an anti-inflammatory phenotype by tissue macrophages and reduces collagen deposition in muscles, with a concomitant reduction of muscle damage. As already observed with other treatments, no improvement in muscle performance was observed in vivo. In conclusion, this work supports the idea that K 3.1 channels play a contributing role in controlling damage-causing cells in DMD. A more complete understanding of their function could lead to the identification of novel therapeutic approaches.

Background: This study aimed to review the data available in the current literature concerning the complications and recurrence of instability following medial patellofemoral ligament (MPFL) reconstruction for patellar instability in young and adolescent patients (those <20 years old). Methods: A systematic review was performed based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Two independent reviewers searched the PubMed, Scopus, EMBASE, and Cochrane databases. The terms “medial patellofemoral ligament” or “MPFL” and “reconstruction” and “young” or “adolescents” or “children” were used. The inclusion criteria for the literature review comprised studies that reported the complications and recurrences of instability in patients who had undergone MPFL reconstruction for patellar instability. Results: In all, 332 patients were included in the review, of which 195 were females (63.5%) and 112 were males (36.5%), and they totaled 352 treated knees. The mean age at the time of the surgery was 14.28 years, and the mean follow-up duration was 30.17 months. A total of 16 (4.5%) complications were reported: one (0.3%) patella fracture, one (0.3%) screw removal due to intolerance, one (0.3%) infection, five (1.4%) wound complications, six (1.7%) subluxations and two (0.6%) instances of post-operative stiffness. A total of 18 (5.1%) recurrences of patellar instability were recorded. Conclusions: MPFL reconstruction in young patients can be considered an effective and safe treatment leading to clinical improvement in terms of recurrence of dislocation. No major complications related to the technique were reported, but a high level of research evidence is required to better evaluate the clinical results in a long-term follow-up.

Providencia stuartii is a member of the Morganellaceae family, notorious for its intrinsic resistance to several antibiotics, including last-resort drugs such as colistin and tigecycline. Between February and March 2022, a four-patient outbreak sustained by P. stuartii occurred in a hospital in Rome. Phenotypic analyses defined these strains as eXtensively Drug-Resistant (XDR). Whole-genome sequencing was performed on the representative P. stuartii strains and resulted in fully closed genomes and plasmids. The genomes were highly related phylogenetically and encoded various virulence factors, including fimbrial clusters. The XDR phenotype was primarily driven by the presence of the blaNDM-1 metallo-β-lactamase alongside the rmtC 16S rRNA methyltransferase, conferring resistance to most β-lactams and every aminoglycoside, respectively. These genes were found on an IncC plasmid that was highly related to an NDM-IncC plasmid retrieved from a ST15 Klebsiella pneumoniae strain circulating in the same hospital two years earlier. Given its ability to acquire resistance plasmids and its intrinsic resistance mechanisms, P. stuartii is a formidable pathogen. The emergence of XDR P. stuartii strains poses a significant public health threat. It is essential to monitor the spread of these strains and develop new strategies for their control and treatment.

Here we describe the evolution of KPC-3-producing ST512 K. pneumoniae isolated at three different times from the same patient of which the last one, from a biliary abscess, showed CZA resistance by KPC-31 production and manifested hmv colony phenotype. Hypervirulent Klebsiella pneumoniae (hv-Kp) isolates are increasingly reported worldwide. Their hypervirulent traits are associated with the presence of rmpA/A2 genes and an hmv. In this study, we identified an hmv-Kp that lacked the rmpA-D cluster but showed an amino acid substitution in the Wzc tyrosin kinase protein, involved in the capsular biosynthesis. This hmv-Kp strain emerged in vivo and evolved resistance to ceftazidime/avibactam resistance in a liver abscess of a patient. Our findings suggest that wzc mutations may be underreported, making it challenging to distinguish hv-Kp from “classic” K. pneumoniae with an hmv phenotype.

In this study, we investigated flotation muds (FM) deriving from the recovery processes of precious metals contained in e-waste (wastes from electronics) and exhausted catalysts. FM consist of an amorphous phase, corresponding to a Ca- and Al-rich silicatic glass, potentially usable as a secondary raw material (SRM) to obtain a final ceramic product (CFM). A high FM amount was used in our ceramic tests, and suitably mixed with variable percentages of other phases. Chemical analysis, phase composition, microstructure, pore pattern and technological properties of the new ceramic products were determined using different analytical techniques, including bulk XRF, XRD, SEM-EDS and µCT. The CFM product predominantly consists of nepheline, pyroxene and wollastonite as the main crystalline phases, with a minor amorphous phase occurring as a compact interstitial matrix. The ceramic product has a porous interconnected microstructure. Nevertheless, this microstructure does not negatively affect the mechanical properties of the ceramic product, as testified by the geo-mechanical tests, revealing good properties in terms of bending and uniaxial strength. These preliminary results point out that FM recycling is feasible, at least at the laboratory scale.

This study presents revised and extended norms for a picture naming test [Laiacona et al. (Arch Neurol Psicol Psichiatr 54:209–248, 1993 )], based on 80 Snodgrass and Vanderwart (J Exp Psychol Human Learn Mem 6:174–215, 1980 ) pictures, devised to detect a categorical dissociation in the naming of items between biological and man-made categories. This survey is based on data from 215 healthy Italian participants. Since males are more frequently reported to have a disproportionate impairment of biological categories, norms have also been separately calculated for males and females and for the two categories of man-made objects and biological entities. Besides providing new normative values based on the Equivalent Scores approach, this study reappraises the interaction between categorical dissociations and sex in the normal population, and discusses some methodological aspects concerning the use of statistical norms.

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management.

Neisseria meningitidis adhesin A (NadA) is a meningococcus surface protein thought to assist in the adhesion of the bacterium to host cells. We have previously shown that NadA also promotes bacterial internalization in a heterologous expression system. Here we have used the soluble recombinant NadA (rNadA) lacking the membrane anchor region to characterize its internalization route in Chang epithelial cells. Added to the culture medium, rNadA internalizes through a PI3K-dependent endocytosis process not mediated by the canonical clathrin or caveolin scaffolds, but instead follows an ARF6-regulated recycling pathway previously described for MHC-I. The intracellular pool of rNadA reaches a steady state level within one hour of incubation and colocalizes in endocytic vesicles with MHC-I and with the extracellularly labeled chaperone Hsp90. Treatment with membrane permeated and impermeable Hsp90 inhibitors 17-AAG and FITC-GA respectively, lead to intracellular accumulation of rNadA, strongly suggesting that the extracellular secreted pool of the chaperone is involved in rNadA intracellular trafficking. A significant number of intracellular vesicles containing rNadA recruit Rab11, a small GTPase associated to recycling endosomes, but do not contain transferrin receptor (TfR). Interestingly, cell treatment with Hsp90 inhibitors, including the membrane-impermeable FITC-GA, abolished Rab11-rNadA colocalization but do not interfere with Rab11-TfR colocalization. Collectively, these results are consistent with a model whereby rNadA internalizes into human epithelial cells hijacking the recycling endosome pathway and recycle back to the surface of the cell via an ARF6-dependent, Rab11 associated and Hsp90-regulated mechanism. The present study addresses for the first time a meningoccoccal adhesin mechanism of endocytosis and suggests a possible entry pathway engaged by N. meningitidis in primary infection of human epithelial cells.