Forensic entomology in homicide cases: study of a corpse found inside a buried vehicle.

Forensic entomology plays a crucial role in death investigations, particularly in estimating the postmortem interval (PMI). This study presents a forensic entomology case involving a corpse found in a buried utility vehicle. The victim was in an advanced state of decomposition, with autopsy findings revealing gunshot wounds. Cadaveric fauna was collected at the scene and during the autopsy. The analysis revealed a diverse insect community, with predominance of Compsomyiops fulvicrura and Piophila casei. The time of development of species like Dermestes maculatus and Necrobia rufipes was used to estimate the minimum PMI. The presence and low abundance of Calliphora vicina, a species preferring lower temperatures, shed light on the seasonal conditions at the time of death and suggested possible body concealment shortly after death. This research is the first to report insects as evidence in a corpse found in a buried vehicle and contributes to the body of knowledge in forensic entomology. The study also suggests that the use of entomological evidence can provide additional information about the season in which the body was concealed, making it a valuable tool in death investigation and crime scene reconstruction. Finally, it emphasizes the need for proper sampling, expert identification, and close collaboration between forensic entomologists and pathologists.

Infectious meningitis. Why are the leptomeninges preferentially involved? Electron microscopic insights.

In infectious meningitis, pathogens preferentially attack the leptomeninges (pia mater and arachnoid) rather than the pachymeninges (dura mater). This study aims to provide ultra-anatomical insights from our extensive collection of electron microscopy images and propose mechanisms, highlighting structures that favor the introduction, adherence, colonization, and proliferation of microorganisms leading to spinal meningitis. Over several years, we analyzed an extensive collection of transmission and scanning electron microscopy images of human spinal meninges captured in our laboratories. Upon examining 378 of those images, we identified potential sites for the iatrogenic or hematogenic introduction and adherence of microorganisms, as well as sites for their colonization and proliferation. These included the outer surface of the spinal dural sac, structures within the epidural space, and the spinal dural sac itself, which comprises compact dura mater with interwoven collagen fibers and tightly bound arachnoid cells. Also, the subdural (extra-arachnoid) compartment, consisting of fragile neurothelial cells prone to rupture under force, formed an acquired spinal subdural space, a new subarachnoid compartment, limited by arachnoid trabeculae, that surrounded the nerve roots and spinal cord and the pia mater. Macrophages, fibroblasts, mast cells, and plasma cells were also observed within the dura mater, arachnoid layer, arachnoid trabeculae, and pia mater. These images illustrate how the characteristics of the meningeal layers could contribute to bacterial adhesion and proliferation at various locations, inducing selective inflammation during (iatrogenic) spinal meningitis. In addition, the images help to explain why magnetic resonance imaging enhancement appears preferentially at specific sites.

Aggregatibacter actinomycetemcomitans Dispersin B: The Quintessential Antibiofilm Enzyme.

The extracellular matrix of most bacterial biofilms contains polysaccharides, proteins, and nucleic acids. These biopolymers have been shown to mediate fundamental biofilm-related phenotypes including surface attachment, intercellular adhesion, and biocide resistance. Enzymes that degrade polymeric biofilm matrix components, including glycoside hydrolases, proteases, and nucleases, are useful tools for studying the structure and function of biofilm matrix components and are also being investigated as potential antibiofilm agents for clinical use. Dispersin B is a well-studied, broad-spectrum antibiofilm glycoside hydrolase produced by Aggregatibacter actinomycetemcomitans. Dispersin B degrades poly-N-acetylglucosamine, a biofilm matrix polysaccharide that mediates biofilm formation, stress tolerance, and biocide resistance in numerous Gram-negative and Gram-positive pathogens. Dispersin B has been shown to inhibit biofilm and pellicle formation; detach preformed biofilms; disaggregate bacterial flocs; sensitize preformed biofilms to detachment by enzymes, detergents, and metal chelators; and sensitize preformed biofilms to killing by antiseptics, antibiotics, bacteriophages, macrophages, and predatory bacteria. This review summarizes the results of nearly 100 in vitro and in vivo studies that have been carried out on dispersin B since its discovery 20 years ago. These include investigations into the biological function of the enzyme, its structure and mechanism of action, and its in vitro and in vivo antibiofilm activities against numerous bacterial species. Also discussed are potential clinical applications of dispersin B.

Nanocomposite system with photoactive phloxine B eradicates resistant Staphylococcus aureus.

Nanomaterials modified with hybrid films functionalized with photoactive compounds can be an effective system to prevent and eradicate biofilms on medical devices. The aim of this research was to extend current knowledge on nanomaterial comprised of polyurethane (PU) modified with a nanocomposite film of organoclay with the functionalized photosensitizer (PS) phloxine B (PhB). Particles of the clay mineral saponite were, at first modified by octadecyltrimethylammonium cations to activate the surface for PhB adsorption. The colloids were filtered to get silicate films on polytetrafluoroethylene membrane filters, which were layered with a liquid mixture of PU precursors. The penetration of PU into the silicate formed a thin nanocomposite film. This nanomaterial demonstrated excellent effectiveness against methicillin-resistant S. aureus (MRSA) resistant to fluoroquinolones (L12 and S61, respectively). It showed more than 1000- and 10 000-fold inhibition of biofilm growth after irradiation with green laser compared to the unmodified PU material. Principal component analysis and multiple linear regression showed that the effectiveness of the nanomaterial was not influenced by virulence factors such as the expression of efflux pumps of the Nor family, the adhesin PIA encoded by the icaADBC operon or the robustness of the biofilms. However, the presence of organoclay, PhB and irradiation had a significant effect on the anti-biofilm properties of the nanocomposite. The anti-microbial properties of the material were strengthened after irradiation, because of high reactive oxygen species release (more than 14-fold compared to non-irradiated sample). Materials based on photoactive molecules can represent a worthwhile pathway towards the development of more complex nanomaterials applicable in various fields of medicine.

Association of Glycoprotein IIIa PlA1/A2 Polymorphism with Risk of Stroke: Updated Meta-Analysis.

Cardiovascular diseases are the main cause of death in the world, with ischemic heart disease (i.e., myocardial infarction) and cerebrovascular disease (i.e., stroke) taking the highest toll. Advances in diagnosis and treatment have led to a significant alleviation of ischemic complications, specifically in the realm of pharmacotherapy and interventional devices, while pharmacogenomics has yet to be fully leveraged to improve the burden of disease. Atherothrombotic events might occur earlier or respond worse to treatment in patients with genetic variants of GP IIb/IIIa. Therefore, we aimed to quantitate the involvement of the PlA2 variant in the risk of cerebral stroke events. A systematic search and meta-analysis were performed by pooling the risks of individual studies. A total of 31 studies comprising 5985 stroke patients and 7886 controls were analyzed. A meta-analysis of four studies on hemorrhagic stroke patients showed no association with the PIA2 rs5918(C) polymorphism in both fixed-effect (OR = 0.90 95%CI [0.71; 1.14]; p = 0.398) and random-effect models (OR = 0.86 95%CI [0.62; 1.20]; p-value = 0.386). The power of this analysis was below <30%, indicating a limited ability to detect a true effect. An analysis of the 28 studies on ischemic stroke revealed a significant association with the PIA2 rs5918(C) allele in both fixed-effect (OR = 1.16 95%CI [1.06; 1.27]; p = 0.001) and random-effect models (OR = 1.20 95%CI [1.04; 1.38]; p-value = 0.012), with a power of >80%. The PIA2 allele was associated with an increased risk of ischemic stroke. No association was found with hemorrhagic stroke, most likely due to the small number of available studies, which resulted in a lack of power.

Spatial transcriptomics analysis identifies a tumor-promoting function of the meningeal stroma in melanoma leptomeningeal disease.

Leptomeningeal disease (LMD) remains a rapidly lethal complication for late-stage melanoma patients. Here, we characterize the tumor microenvironment of LMD and patient-matched extra-cranial metastases using spatial transcriptomics in a small number of clinical specimens (nine tissues from two patients) with extensive in vitro and in vivo validation. The spatial landscape of melanoma LMD is characterized by a lack of immune infiltration and instead exhibits a higher level of stromal involvement. The tumor-stroma interactions at the leptomeninges activate tumor-promoting signaling, mediated through upregulation of SERPINA3. The meningeal stroma is required for melanoma cells to survive in the cerebrospinal fluid (CSF) and promotes MAPK inhibitor resistance. Knocking down SERPINA3 or inhibiting the downstream IGR1R/PI3K/AKT axis results in tumor cell death and re-sensitization to MAPK-targeting therapy. Our data provide a spatial atlas of melanoma LMD, identify the tumor-promoting role of meningeal stroma, and demonstrate a mechanism for overcoming microenvironment-mediated drug resistance in LMD.

The meninges.

The dura was first described in ancient Egypt. Hippocrates insisted that it should be protected and not penetrated. Celsus proposed an association between clinical findings and meningeal damage. Galen proposed that the dura was attached only at the sutures, and he was the first to describe the pia in humans. In the Middle Ages, new interest in the management of meningeal injuries arose, with renewed interest in relating clinical changes to intracranial injuries. These associations were neither consistent nor accurate. The Renaissance brought little change. It was in the 18th century that it became clear that the indication for opening the cranium following trauma was to relieve pressure from hematomas. Moreover, the important clinical findings on which to base an indication for intervention were changes in the level of consciousness.

Polysaccharide intercellular adhesin and proper phospholipid composition are important for aggregation in Tetragenococcus halophilus SL10.

Aggregating strains of Tetragenococcus halophilus tend to be trapped during soy sauce mash-pressing process and are, therefore, critical for clear soy sauce production. However, the precise molecular mechanism involved in T. halophilus aggregation remains elusive. In previous studies, we isolated a number of aggregating strains, including T. halophilus AB4 and AL1, and showed that a cell surface proteinaceous aggregation factor is responsible for their aggregation phenotype. In the present study, we explored the role of polysaccharide intercellular adhesin (PIA) in aggregate formation in T. halophilus SL10, isolated from soy sauce. SL10 exhibited similar aggregation to AB4 and AL1 but formed a non-uniform precipitate with distinctive wrinkles at the bottom of the test tube, unlike AB4 and AL1. Insertion sequence mutations in each gene of the ica operon diminished aggregation and PIA production, highlighting the critical role of IcaADBC-mediated PIA production in T. halophilus aggregation. Furthermore, two non-aggregating cardiolipin synthase (cls) gene mutants with intact ica operon did not produce detectable PIA. Phospholipid composition analysis in cls mutants revealed a decrease in cardiolipin and an increase in phosphatidylglycerol levels, highlighting the association between phospholipid composition and PIA production. These findings provide evidence for the pivotal role of cls in PIA-mediated aggregation and lay the foundation for future studies to understand the intricate networks of the multiple aggregation factors governing microbial aggregation.IMPORTANCEAggregation, commonly observed in various microbes, triggers biofilm formation in pathogenic variants and plays a beneficial role in efficient food production in those used for food production. Here, we showed that Tetragenococcus halophilus, a microorganism used in soy sauce fermentation, forms aggregates in a polysaccharide intercellular adhesin (PIA)-mediated manner. Additionally, we unveiled the relationship between phospholipid composition and PIA production. This study provides evidence for the presence of aggregation factors in T. halophilus other than the proteinaceous aggregation factor and suggests that further understanding of the coordinated action of these factors may improve clarified soy sauce production.

Characterization of primary human leptomeningeal cells in 2D culture.

Maintaining the integrity of brain barriers is critical for a healthy central nervous system. While extensive research has focused on the blood-brain barrier (BBB) of the brain vasculature and blood-cerebrospinal fluid barrier (BCSFB) of the choroid plexus, the barriers formed by the meninges have not received as much attention. These membranes create a barrier between the brain and cerebrospinal fluid (CSF), as well as between CSF and blood. Recent studies have revealed that this barrier has been implicated in the development of neurological and immunological disorders. In order to gain a deeper comprehension of the functioning and significance of the meningeal barriers, sophisticated models of these barriers, need to be created. The aim of this paper is to investigate the characteristics of commercially available primary leptomeningeal cells (LMCs) that form the meningeal barriers, in a cultured environment, including their morphology, proteomics, and barrier properties, and to determine whether passaging of these cells affects their behaviour in comparison to their in vivo state. The results indicate that higher passage numbers significantly alter the morphology and protein localisation and expression of the LMCs. Furthermore, the primary cell culture co-stained for S100A6 and E-cadherin suggesting it is a co-culture of both pial and arachnoid cells. Additionally, cultured LMCs showed an increase in vimentin and cytokeratin expression and a lack of junctional proteins localisation on the cell membrane, which could suggest loss of epithelial properties due to culture, preventing barrier formation. This study shows that the LMCs may be a co-culture of pial and arachnoid cells, that the optimal LMC passage range is between passages two and five for experimentation and that the primary human LMCs form a weak barrier when in culture.

Ex vivo observation of Pythium insidiosum-antigen treated neutrophils on three Pythium insidiosum strains isolated from vascular pythiosis patients.

The mechanisms of Pythium insidiosum-antigen (PIA) immunotherapy activating a patient's immune system are unknown. We evaluated the interleukin-8 (IL-8) serum levels during P. insidiosum infection and after vaccination with PIA in vascular pythiosis cases. Furthermore, we studied the anti-P. insidiosum activity of neutrophils stimulated with various concentrations of PIA ex vivo in 3 strains of P. insidiosum isolated from vascular pythiosis patients. IL-8 serum levels were evaluated using the ELISA technique. We assessed the effect of PIA-stimulated neutrophils on the viability of zoospores using MTT assay, visualized neutrophil extracellular trap (NET) formation via microscopy, and measured the levels of double-stranded DNA (dsDNA) using PicoGreen dsDNA quantitation assay in 3 strains of P. insidiosum isolated from vascular pythiosis patients. Serum levels of IL-8 gradually lowered from the early to the end phases of vaccination with PIA among the surviving group of vascular pythiosis cases. Neutrophils stimulated with 0.01 µg/ml PIA reduced zoospore viability significantly compared to PIA-unstimulated neutrophils for strain 1 and strain 3 (p < .05). Neutrophils stimulated with 0.01, 0.1, 1, and 10 µg/ml PIA exhibited significantly lower zoospore viability than PIA-unstimulated neutrophils for strain 2 (p < .05). IL-8 can be used as a biomarker for monitoring vascular pythiosis cases treated with the PIA vaccine. Also, anti-P. insidiosum activity of PIA-stimulated neutrophils was probably due to the disruption of cellular activity in zoospores rather than the mechanisms based on the formation of NETs.

Novel small-molecule compound YH7 inhibits the biofilm formation of Staphylococcus aureus in a sarX-dependent manner.

The emergence of antibiotic-resistant and biofilm-producing Staphylococcus aureus isolates presents major challenges for treating staphylococcal infections. Biofilm inhibition is an important anti-virulence strategy. In this study, a novel maleimide-diselenide hybrid compound (YH7) was synthesized and demonstrated remarkable antimicrobial activity against methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) in both planktonic cultures and biofilms. The minimum inhibitory concentration (MIC) of YH7 for S. aureus isolates was 16 µg/mL. Quantification of biofilms demonstrated that the sub-MIC (4 µg/mL) of YH7 significantly inhibits biofilm formation in both MSSA and MRSA. Confocal laser scanning microscopy analysis further confirmed the biofilm inhibitory potential of YH7. YH7 also significantly suppressed bacterial adherence to A549 cells. Moreover, YH7 treatment significantly inhibited S. aureus colonization in nasal tissue of mice. Preliminary mechanistic studies revealed that YH7 exerted potent biofilm-suppressing effects by inhibiting polysaccharide intercellular adhesin (PIA) synthesis, rather than suppressing bacterial autolysis. Real-time quantitative PCR data indicated that YH7 downregulated biofilm formation-related genes (clfA, fnbA, icaA, and icaD) and the global regulatory gene sarX, which promotes PIA synthesis. The sarX-dependent antibiofilm potential of YH7 was validated by constructing S. aureus NCTC8325 sarX knockout and complementation strains. Importantly, YH7 demonstrated a low potential to induce drug resistance in S. aureus and exhibited non-toxic to rabbit erythrocytes, A549, and BEAS-2B cells at antibacterial concentrations. In vivo toxicity assays conducted on Galleria mellonella further confirmed that YH7 is biocompatible. Overall, YH7 demonstrated potent antibiofilm activity supports its potential as an antimicrobial agent against S. aureus biofilm-related infections. IMPORTANCE Biofilm-associated infections, characterized by antibiotic resistance and persistence, present a formidable challenge in healthcare. Traditional antibacterial agents prove inadequate against biofilms. In this study, the novel compound YH7 demonstrates potent antibiofilm properties by impeding the adhesion and the polysaccharide intercellular adhesin production of Staphylococcus aureus. Notably, its exceptional efficacy against both methicillin-resistant and methicillin-susceptible strains highlights its broad applicability. This study highlights the potential of YH7 as a novel therapeutic agent to address the pressing issue of biofilm-driven infections.

The biofilm proteome of Staphylococcus aureus and its implications for therapeutic interventions to biofilm-associated infections.

Staphylococcus aureus is a major healthcare concern due to its ability to inflict life-threatening infections and evolve antibiotic resistance at an alarming pace. It is frequently associated with hospital-acquired infections, especially device-associated infections. Systemic infections due to S. aureus are difficult to treat and are associated with significant mortality and morbidity. The situation is worsened by the ability of S. aureus to form social associations called biofilms. Biofilms embed a community of cells with the ability to communicate with each other and share resources within a polysaccharide or protein matrix. S. aureus establish biofilms on tissues and conditioned abiotic surfaces. Biofilms are hyper-tolerant to antibiotics and help evade host immune responses. Biofilms exacerbate the severity and recalcitrance of device-associated infections. The development of a biofilm involves various biomolecules, such as polysaccharides, proteins and nucleic acids, contributing to different structural and functional roles. Interconnected signaling pathways and regulatory molecules modulate the expression of these molecules. A comprehensive understanding of the molecular biology of biofilm development would help to devise effective anti-biofilm therapeutics. Although bactericidal agents, antimicrobial peptides, bacteriophages and nano-conjugated anti-biofilm agents have been employed with varying levels of success, there is still a requirement for effective and clinically viable anti-biofilm therapeutics. Proteins that are expressed and utilized during biofilm formation, constituting the biofilm proteome, are a particularly attractive target for anti-biofilm strategies. The proteome can be explored to identify potential anti-biofilm drug targets and utilized for rational drug discovery. With the aim of uncovering the biofilm proteome, this chapter explores the mechanism of biofilm formation and its regulation. Furthermore, it explores the antibiofilm therapeutics targeted against the biofilm proteome.

Cetoacidosis diabética secundaria a inmunoterapia / Diabetic ketoacidosis secondary to immunotherapy

Resumen Los inhibidores de puntos de control inmune (ICIs) son anticuerpos monoclonales cada vez más utilizados en tratamientos oncológicos. A medida que aumenta la experiencia en el uso de inmunoterapia, se conoce cada vez más su perfil de seguridad y los efectos adversos inmunomediados. Entre ellos se encuentra la cetoaci dosis diabética (CAD), complicación infrecuente, grave y potencialmente mortal. En este trabajo describimos los casos de tres pacientes que se presentaron con episo dios de CAD durante el tratamiento con ICIs, dos de los cuales manifestaron con formas fulminantes, llevando un curso agudo con valores de hemoglobina glicosilada inicialmente normales. Asimismo, realizamos una revi sión de la literatura sobre la CAD asociada a ICIs a fines de resaltar la importancia de advertir estas complica ciones potencialmente fatales e instaurar rápidamente la terapéutica apropiada.

Abstract Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that are increasingly used in cancer treat ments. As experience in the use of immunotherapy increases, more is known about its safety profile and immune-mediated adverse effects. Among them is dia betic ketoacidosis (DKA), a rare but serious fatal compli cation of treatment. In this paper we describe the cases of three patients who presented with episodes of DKA during treatment with ICIs, two of which manifested with fulminant forms, leading to an acute course with initially normal glycosylated hemoglobin values. In ad dition, we conducted a review of the literature on DKA associated with ICIs in order to highlight the importance of noticing these potentially fatal complications and promptly establishing appropriate therapy.

Differences in Biofilm Formation by Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Strains.

Staphylococcus aureus (S. aureus) is a common pathogen involved in community- and hospital-acquired infections. Its biofilm formation ability predisposes it to device-related infections. Methicillin-resistant S. aureus (MRSA) strains are associated with more serious infections and higher mortality rates and are more complex in terms of antibiotic resistance. It is still controversial whether MRSA are indeed more virulent than methicillin-susceptible S. aureus (MSSA) strains. A difference in biofilm formation by both types of bacteria has been suggested, but how only the presence of the SCCmec cassette or mecA influences this phenotype remains unclear. In this review, we have searched for literature studying the difference in biofilm formation by MRSA and MSSA. We highlighted the relevance of the icaADBC operon in the PIA-dependent biofilms generated by MSSA under osmotic stress conditions, and the role of extracellular DNA and surface proteins in the PIA-independent biofilms generated by MRSA. We described the prominent role of surface proteins with the LPXTG motif and hydrolases for the release of extracellular DNA in the MRSA biofilm formation. Finally, we explained the main regulatory systems in S. aureus involved in virulence and biofilm formation, such as the SarA and Agr systems. As most of the studies were in vitro using inert surfaces, it will be necessary in the future to focus on biofilm formation on extracellular matrix components and its relevance in the pathogenesis of infection by both types of strains using in vivo animal models.

Intracranial Angioplasty via Type II Proatlantal Intersegmental Artery.

A proatlantal intersegmental artery (PIA) is an exceedingly rare primitive anastomosis between the carotid and vertebrobasilar circulations. PIAs may be accompanied by ipsilateral or bilateral vertebral artery (VA) agenesis and can originate from the cervical internal carotid artery (ICA, type I) or external carotid artery (ECA, type II) before eventually joining the vertebrobasilar system. Several authors have described this anomaly in different clinical scenarios, but to our knowledge, there are no studies documenting VA angioplasty through a type II PIA in the setting of vertebrobasilar stroke. We present the case of vertebrobasilar stroke in which the right VA did not originate from the right subclavian artery but instead from the ECA. The patient was subsequently determined to have a type II PIA. We performed right VA angioplasty via the PIA, followed by partial restoration of vertebrobasilar blood flow. This is the first documented case of intracranial vertebral angioplasty through a type II PIA and serves as a reminder for neuroendovascular surgeons about persistent fetal circulation. In such instances, an angiogram of both the ICA and ECA should be performed to exclude right VA stenosis and visualize persistent fetal circulation. This case underscores the complexity of arterial thrombotic events, the beneficial role of endovascular intervention, and the necessity of future studies to identify the optimal treatment methods for vertebrobasilar stroke.

A novel small-molecule compound S-342-3 effectively inhibits the biofilm formation of Staphylococcus aureus.

IMPORTANCE: Biofilms are an important virulence factor in Staphylococcus aureus and are characterized by a structured microbial community consisting of bacterial cells and a secreted extracellular polymeric matrix. Inhibition of biofilm formation is an effective measure to control S. aureus infection. Here, we have synthesized a small molecule compound S-342-3, which exhibits potent inhibition of biofilm formation in both MRSA and MSSA. Further investigations revealed that S-342-3 exerts inhibitory effects on biofilm formation by reducing the production of polysaccharide intercellular adhesin and preventing bacterial adhesion. Our study has confirmed that the inhibitory effect of S-342-3 on biofilm is achieved by downregulating the expression of genes responsible for biofilm formation. In addition, S-342-3 is non-toxic to Galleria mellonella larvae and A549 cells. Consequently, this study demonstrates the efficacy of a biologically safe compound S-342-3 in inhibiting biofilm formation in S. aureus, thereby providing a promising antibiofilm agent for further research.

Molecular anatomy of adult mouse leptomeninges.

Leptomeninges, consisting of the pia mater and arachnoid, form a connective tissue investment and barrier enclosure of the brain. The exact nature of leptomeningeal cells has long been debated. In this study, we identify five molecularly distinct fibroblast-like transcriptomes in cerebral leptomeninges; link them to anatomically distinct cell types of the pia, inner arachnoid, outer arachnoid barrier, and dural border layer; and contrast them to a sixth fibroblast-like transcriptome present in the choroid plexus and median eminence. Newly identified transcriptional markers enabled molecular characterization of cell types responsible for adherence of arachnoid layers to one another and for the arachnoid barrier. These markers also proved useful in identifying the molecular features of leptomeningeal development, injury, and repair that were preserved or changed after traumatic brain injury. Together, the findings highlight the value of identifying fibroblast transcriptional subsets and their cellular locations toward advancing the understanding of leptomeningeal physiology and pathology.

European Projects for Patients with Dementia and Their Caregivers.

As we all know there is no treatment that can stop or delay the progression of dementia. The treatment we use is only symptomatic. EFNS (European Federation of Neurological Societies) recommendations for dementia prevention by Sorbi et al. (2012) concluded that there is no treatment, no lifestyle, which could have an effect on prevention or delay of onset of different forms of dementia until today. The future studies in prevention must recruit younger people, larger sample, and for longer period. The last 10 years we have run, in collaboration with organizations in different European countries, many projects in order to support patients with neurodegenerative diseases, mainly patients with dementia and their caregivers. The first project was a 2-year prospective cohort study of antidementia drug non-persistency in mild-to-moderate Alzheimer's disease (AD) in Europe: predictors of discontinuation and switch in the ICTUS (Impact of Cholinergic Treatment USe) study, an FP5 project with 1380 patients. Five studies were published. The second project was DESCRIPA study, an FP5 project to DEvelopment of Screening guidelines and clinical CRIteria for Predementia Alzheimer's disease, with 881 patients with mild cognitive impairment (MCI). LLM (Long Lasting Memories) and VRADA (A virtual reality application for the exercise of dementia and Alzheimer patients) are two projects that include body and cognitive exercise for health for the elderly and patients with mild cognitive impairment. The next is the RECAGE (REspectful Caring for the AGitated Elderly) project (Horizon 2020), a prospective cohort study for coping with behavioral and psychological symptoms of dementia. With six European universities we finished a very interesting FP6 project, the AddNeuroMed one, which gives even now information about the progression of normal elderly MCI and AD patients, in collaboration with other consortia. A very interesting Innovative Medicines Initiative (IMI) project about digital biomarkers was entitled Remote Assessment of Disease and Relapse-Alzheimer's Disease (RADAR project). The main goal of this project was the development and validation of technology-enabled, quantitative and sensitive measures of functional decline in people with early-stage AD. A running project is an Erasmus+ one in the higher education field, "Genetic counseling in European universities: The case of neurodegenerative diseases" (GECONEU project). The target of this study is to develop an online course for university students focusing on genetic counseling, and support people and society to better understand the aims of genetic testing and the usefulness of genetic counseling by involving students in an innovative learning and teaching setting. AD-gaming, BRIDGE, iCONNECT (Intergenerational CONtact between studeNts and people with dEmentia through CreaTive education), E.L.So.M.C.I (English Lessons with the Use of Songs for People with Mild Cognitive Impairment), Games4CoSkills, and De-Sign are all Erasmus+ projects that aim to improve the quality of life of patients with MCI or dementia. Story2remember, Dementia right, ASPAD (Augmentation of the Support of Patients suffering from Alzheimer's Disease and their caregivers), INFOCARE (Supporting Informal Caregivers of People with Dementia), S.IN.CA.L.A (Supporting Informal Carers: A Whole-Family and Life course Approach), and PIA (Peer support workers as an Innovative force in Advocacy in dementia care) are all Erasmus+ projects for training and supporting caregivers of patients with dementia.

Adult cervicothoracic subpial fibrolipoma without dysraphism: An extremely rare case report.

INTRODUCTION: Spinal tumors constitute 15 % of all tumors in the central nervous system. Pain is often the initial symptom, which can be localized, nocturnal, or radiated to the arms and/or limbs. We report a rare case with a subpial lipoma in the cervicothoracic spine and review the current literature. CASE PRESENTATION: A 22-year-old female presented with the chief complaint of tetraparesis for three months before admission. Magnetic resonance imaging revealed an intradural tumor on the fifth cervical to fourth thoracic vertebrae. She underwent a laminectomy to remove the tumor completely. Histopathological examination revealed a proliferation of mature fat cells amongst fibrous connective tissue. Surrounding nerve fibers and erythrocyte-filled blood vessels were also found, suggesting a subpial fibrolipoma. Postoperatively, there was an improvement in muscle strength six weeks after surgery. Motoric strength was grade 5 for the upper extremities and grade 4 for the lower extremities. DISCUSSION: In this patient, cervicothoracic laminectomy and tumor removal were performed without instrumentation. Total tumor resection is the primary goal when removing a pathological lesion. However, this depends on the lesion's adhesion to the surrounding tissue. Therefore, partial tumor resection may be possible, given the neurological complications that can occur. CONCLUSION: Because subpial lipomas are rare, their treatment is highly specialized. An assessment of the patient's physical condition and imaging assessments can provide information about potential treatment strategies and outcomes.

Roles of the Crp/Fnr Family Regulator ArcR in the Hemolysis and Biofilm of Staphylococcus aureus.

Staphylococcus aureus is an opportunistic human pathogen that is often involved in severe infections such as pneumonia and sepsis in which bacterial virulence factors play a key role. Infections caused by S. aureus are often difficult to eradicate, particularly when they are associated with biofilm. The physiological roles of the Crp/Fnr family regulator ArcR are elusive in S. aureus. In this study, it was found that the deletion of arcR increased the hemolytic ability and biofilm formation in S. aureus. Differential gene expression analysis by RNA-seq and real-time quantitative reverse transcription PCR showed that genes associated with hemolytic ability (hla and hlb) and biofilm formation (icaA, icaB, icaC and icaD) were significantly upregulated compared with those in the wild-type strain. The results revealed that ArcR regulated the expression of the hla and ica operon by binding to their promoter regions, respectively. This study provided new insights into the functional importance of ArcR in regulating the virulence and biofilm of S. aureus.