Chemiresistors Based on Hybrid Nanostructures Obtained from Graphene and Conducting Polymers with Potential Use in Breath Methane Detection Associated with Irritable Bowel Syndrome.

This paper describes the process of producing chemiresistors based on hybrid nanostructures obtained from graphene and conducting polymers. The technology of graphene presumed the following: dispersion and support stabilization based on the chemical vapor deposition technique; transfer of the graphene to the substrate by spin-coating of polymethyl methacrylate; and thermal treatment and electrochemical delamination. For the process at T = 950 °C, a better settlement of the grains was noticed, with the formation of layers predominantly characterized by peaks and not by depressions. The technology for obtaining hybrid nanostructures from graphene and conducting polymers was drop-casting, with solutions of Poly(3-hexylthiophene (P3HT) and Poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-bithiophene] (F8T2). In the case of F8T2, compared to P3HT, a 10 times larger dimension of grain size and about 7 times larger distances between the peak clusters were noticed. To generate chemiresistors from graphene-polymer structures, an ink-jet printer was used, and the metallization was made with commercial copper ink for printed electronics, leading to a structure of a resistor with an active surface of about 1 cm2. Experimental calibration curves were plotted for both sensing structures, for a domain of CH4 of up to 1000 ppm concentration in air. A linearity of the curve for the low concentration of CH4 was noticed for the graphene structure with F8T2, presenting a sensitivity of about 6 times higher compared with the graphene structure with P3HT, which makes the sensing structure of graphene with F8T2 more feasible and reliable for the medical application of irritable bowel syndrome evaluation.

Lipid-Derived Biomarkers as Therapeutic Targets for Chronic Coronary Syndrome and Ischemic Stroke: An Updated Narrative Review.

The incidence and prevalence of cardiac and cerebrovascular diseases are constantly increasing, with chronic coronary syndrome and ischemic stroke as the leading causes of morbidity and mortality worldwide. According to current knowledge, the heart-brain axis is more than a theoretical concept, with many common pathophysiological mechanisms involved in the onset and evolution of both coronary and cerebral ischemia. Moreover, the focus is on the prevention and early intervention of risk factors in searching for targeted and personalized medical treatment. In this context, this narrative review aims to offer, in a didactic and practice-oriented manner, an up-to-date overview of the role played by lipid-derived biomarkers (from low-density lipoprotein cholesterol to oxylipin and apolipoproteins) in chronic coronary syndrome and ischemic stroke. Firstly, the authors highlight, via relevant epidemiological data, the significant burden of chronic coronary syndrome and ischemic stroke in the general population, thus explaining the need for updated information on this topic. Subsequently, the most important lipid-derived biomarkers and their multiple roles in the pathogenesis of these two disorders are listed. Currently available and experimental targeted therapies based on these lipid-derived biomarkers are presented in the final part of this paper, representing this manuscript's original and novel input.

Is prior knowledge essential? Additional training opportunities restore sleep-associated memory benefits under conditions of low prior knowledge.

Sleep-mediated memory benefits are modulated by several factors. Prior knowledge is assumed critical for consolidation during sleep, despite inconclusive empirical findings. Additionally, prior knowledge facilitates encoding, leading to differences in memory strength already before the retention filled with sleep. We tested whether increasing memory strength of unfamiliar learning material pre-sleep can restore sleep-mediated memory benefits in cases of low prior knowledge. One-hundred and fifty-four healthy young students learned translations of Dutch words. One group was German-speaking, the other French-speaking. As French is less similar to Dutch than German, we expected a lower prior knowledge in French participants. We manipulated memory strength during pre-sleep encoding by varying the number of learning possibilities (one and two rounds for German-speaking, two and three rounds for French-speaking participants). When using the same learning paradigm for both groups (two rounds), lower prior knowledge modulated sleep-mediated memory benefits: French-speaking participants showed no advantage in memory after nighttime sleep compared with daytime wakefulness. In contrast, German-speaking participants showed robust sleep-mediated memory benefits. However, increasing memory strength before sleep restored sleep-mediated memory benefits in French subjects to a level of German-speaking participants. Conversely, reducing the training in German-speaking participants reduced sleep-mediated memory benefits. Our results show that prior knowledge and memory strength strongly modulate sleep-associated memory benefits. However, in cases of low prior knowledge, sleep-mediated memory benefits can be successfully restored by additional training. While prior knowledge might modulate encoding and consolidation processes more generally, its effect on sleep-specific processes of memory retention might be less important than previously assumed.

Efficient removal of antibodies to adeno-associated viruses by immunoadsorption.

BACKGROUND: Gene therapies based on adeno-associated viruses (AAV) are a therapeutic option to successfully treat monogenetic diseases. However, the influence of pre-existing immunity to AAV can compromise the application of AAV gene therapy, most notably by the presence of neutralizing antibodies (NAb) to AAV. METHODS: In the following study, we investigated to what extent the treatment by immunoadsorption (IA) would reduce the levels of human anti-AAV antibodies to AAV2 and AAV5. To that end, we screened blood sera from 40 patients receiving IA treatment because of underlying autoimmune disease or transplant rejection, with detectable AAV-antibodies in 23 patients (22 by NAb detection, and 1 additionally by anti-AAV5 ELISA analysis). RESULTS: Our results show that IA efficiently depleted anti-AAV2 NAb with a mean reduction of 3.92 ± 1.09 log2 titer steps (93.4%) after three to five single IA treatments, 45% of seropositive subjects had an anti-AAV2 titer below the threshold titer of 1:5 after the IA treatment series. Anti-AAV5 NAb were reduced to below the threshold titer of 1:5 in all but one of five seropositive subjects. Analysis of total anti-AAV5 antibodies by ELISA demonstrated an anti-AAV5 antibody reduction over the IA treatment series of 2.67 ± 1.16 log2 titer steps (84.3%). CONCLUSION: In summary, IA may represent a safe strategy to precondition patients with pre-existing anti-AAV antibodies to make this population eligible for an effective AAV-based gene therapy.

Does Gender-Affirming Hormonal Treatment Affect 30-Year Cardiovascular Risk in Transgender Persons? A Two-Year Prospective European Study (ENIGI).

BACKGROUND: Cardiovascular (CV) implications of long-term gender affirming hormonal treatment (GAHT) in transgender individuals still remain largely unknown. AIM: To evaluate changes in the 30-year Framingham cardiovascular disease (CVD) risk in a large cohort of transgender individuals after the start of GAHT. METHODS: In a multicenter prospective study, a consecutive series of 309 participants (165 transmen and 144 transwomen) was evaluated during a 2-year follow-up. Prospectively, after the start of GAHT a physical examination was performed and blood samples were drawn. CVD risk was calculated for each person, according to the Framingham 30-year CVD risk estimate. MAIN OUTCOME MEASURE: Changes in CV risk factors and 30-year Framingham CVD risk during GAHT. CLINICAL IMPLICATIONS: In transmen testosterone-induced lipid profile alterations may have a clinical relevance on the individual long-term CVD risk. STRENGTHS & LIMITATIONS: The strength of the present study is the possibility to predict long-term CV outcomes in transgender individuals receiving GAHT based on a short observation; whereas the main limitation is that CVD risk prospective changes mainly represent the expression of risk factors changes during GAHT. RESULTS: In transwomen a significant decrease in triglycerides, total cholesterol and LDL-cholesterol was observed during the 2-year follow-up (P < .05), whereas unfavorable lipid changes - such as increased total cholesterol, triglycerides, and LDL cholesterol levels and decreased HDL cholesterol levels (P < .05)- occurred after the start of GAHT in transmen. These changes in risk factors led to an increase in the risk of general and hard CVD events based on lipid profile over time in transmen (P = .001 and P = .005, respectively). No significant changes in general and hard CVD risk based on lipid profile were observed in transwomen over time. CONCLUSIONS: Our findings confirmed the unfavorable lipid changes in transmen after the start of GAHT even during a longer follow-up, empathizing the potential clinical impact of these modifications on individual long-term CVD risk. Cocchetti C, Castellini G, Iacuaniello D, et al. Does Gender-Affirming Hormonal Treatment Affect 30-Year Cardiovascular Risk in Transgender Persons? A Two-Year Prospective European Study (ENIGI). J Sex Med 2021;18:821-829.

Performance of Hepatitis E Virus (HEV)-antibody tests: a comparative analysis based on samples from individuals with direct contact to domestic pigs or wild boar in Germany.

In Europe, Hepatitis E virus (HEV) genotype 3 causes most human infections, and domestic pigs and wild boar represent the main reservoirs. Contact to these animals represents one source of human infection. However, interpretation of studies is challenged in the absence of a serological gold standard. Hence, this study compared results of different HEV immunoassays. Plasma samples from 139 individuals who had professional contact to pigs (veterinarians, meat inspectors, slaughterhouse workers; n = 114) or hunted regularly (n = 25) were tested with assays specific for HEV IgG, HEV IgM, HEV IgA, and total HEV immunoglobulin as well as for viral RNA. Furthermore, overall HEV IgG was defined (i.e., two of three IgG assays reveal the same result) to compare serological findings. Borderline results were always quoted as positive. For IgG, apparent prevalence was higher in Wantai (48.2%) compared to Euroimmun (11.5%) and Mikrogen assays (17.3%) (p = 0.0001). The overall IgG prevalence was estimated to be 18.7%. For total Ig, Wantai (40.3%) also yielded higher prevalence than Euroimmun (15.8%) (p = 0.0001). The HEV IgM prevalence ranged from 0% (Euroimmun) to 4.3% (Mikrogen). Four percent of individuals tested IgA positive, whilst none harboured HEV RNA. Our results support previous studies that the higher IgG prevalence estimated with the Wantai assay result from a higher sensitivity of this test. However, further studies are needed to verify specificity given the challenge of defining true negative samples. The high percentage of individuals with HEV IgG observed in this study underlines that direct contact to pigs represents a risk factor for HEV infection.

Boosting Vocabulary Learning by Verbal Cueing During Sleep.

Reactivating memories during sleep by re-exposure to associated memory cues (e.g., odors or sounds) improves memory consolidation. Here, we tested for the first time whether verbal cueing during sleep can improve vocabulary learning. We cued prior learned Dutch words either during non-rapid eye movement sleep (NonREM) or during active or passive waking. Re-exposure to Dutch words during sleep improved later memory for the German translation of the cued words when compared with uncued words. Recall of uncued words was similar to an additional group receiving no verbal cues during sleep. Furthermore, verbal cueing failed to improve memory during active and passive waking. High-density electroencephalographic recordings revealed that successful verbal cueing during NonREM sleep is associated with a pronounced frontal negativity in event-related potentials, a higher frequency of frontal slow waves as well as a cueing-related increase in right frontal and left parietal oscillatory theta power. Our results indicate that verbal cues presented during NonREM sleep reactivate associated memories, and facilitate later recall of foreign vocabulary without impairing ongoing consolidation processes. Likewise, our oscillatory analysis suggests that both sleep-specific slow waves as well as theta oscillations (typically associated with successful memory encoding during wakefulness) might be involved in strengthening memories by cueing during sleep.

Cross-sex hormone therapy in trans persons is safe and effective at short-time follow-up: results from the European network for the investigation of gender incongruence.

INTRODUCTION: Data on the effects of cross-sex hormone therapy (CHT) are limited due to the low prevalence of gender dysphoria, small number of subjects treated at each center, lack of prospective studies, and wide variations in treatment modalities. AIM: The aim of this study is to report the short-term effects of CHT on hormonal and clinical changes, side effects, and adverse events in trans men (female-to-male gender dysphoric persons) and trans women (male-to-female gender dysphoric persons). METHODS: This was a multicenter 1-year prospective study in 53 trans men and 53 trans women. Trans men received injections of testosterone undecanoate every 3 months. Trans women younger than 45 years received 50 mg cyproterone acetate (CA) and 4 mg estradiol valerate daily, whereas those older than 45 years received 50 mg CA daily together with 100 µg/24 hours transdermal 17-ß estradiol. MAIN OUTCOME MEASURES: Sex steroids, prolactin, liver enzymes, lipids, hematocrit, blood pressure, anthropometrics, Ferriman and Gallwey score, and global acne grading scale were measured. Side effects, adverse events, and desired clinical changes were examined. RESULTS: No deaths or severe adverse events were observed. Two trans men developed erythrocytosis, and two had transient elevation of the liver enzymes. Trans men reported an increase in sexual desire, voice instability, and clitoral pain (all P ≤ 0.01). Testosterone therapy increased acne scores, facial and body hair, and prevalence of androgenetic alopecia. Waist-hip ratio, muscle mass, triglycerides, total cholesterol (C), and LDL-C increased, whereas total body fat mass and HDL-C decreased. Three trans women experienced transient elevation of liver enzymes. A significant increase in breast tenderness, hot flashes, emotionality, and low sex drive was observed (all P ≤ 0.02). Fasting insulin, total body fat mass, and prolactin levels increased, and waist-hip ratio, lean mass, total C, and LDL-C decreased. CONCLUSIONS: Current treatment modalities were effective and carried a low risk for side effects and adverse events at short-time follow-up.

The impact of palliative care on the frailty-stroke continuum: from theoretical concepts to practical aspects.

With a constant increase in prevalence and incidence worldwide, stroke remains a public health issue in the 21st century. Additionally, population aging inevitably leads to increased vulnerability in the general population, a clinical state known as frailty. While there are adequate guidelines on the treatment of stroke in the acute setting, there are a lot of gaps regarding the chronic management of stroke patients, particularly the frail ones. From the therapeutic point of view, palliative care could be the key to offering complex and individualized treatment to these frail chronic stroke patients. In the context of the heterogeneous data and incomplete therapeutic guidelines, this article provides a new and original perspective on the topic, aiming to increase awareness and understanding and improve palliative care management in stroke patients. Based on current knowledge, the authors describe a new concept called the frailty-stroke continuum and offer a detailed explanation of the intricate stroke-frailty connection in the first part. After understanding the role of palliative care in managing this kind of patients, the authors discuss the most relevant practical aspects aiming to offer an individualized framework for daily clinical practice. The novel approach consists of developing a four-step scale for characterizing frail stroke patients, with the final aim of providing personalized treatment and correctly evaluating prognosis. By pointing out the limitations of current guidelines and the challenges of new research directions, this article opens the pathway for the better evaluation of frail stroke patients, offering a better perception of patients' prognosis.

Spinal Cord Injury Management Based on Microglia-Targeting Therapies.

Spinal cord injury is a complicated medical condition both from the clinician's point of view in terms of management and from the patient's perspective in terms of unsatisfactory recovery. Depending on the severity, this disorder can be devastating despite the rapid and appropriate use of modern imaging techniques and convenient surgical spinal cord decompression and stabilization. In this context, there is a mandatory need for novel adjunctive therapeutic approaches to classical treatments to improve rehabilitation chances and clinical outcomes. This review offers a new and original perspective on therapies targeting the microglia, one of the most relevant immune cells implicated in spinal cord disorders. The first part of the manuscript reviews the anatomical and pathophysiological importance of the blood-spinal cord barrier components, including the role of microglia in post-acute neuroinflammation. Subsequently, the authors present the emerging therapies based on microglia modulation, such as cytokines modulators, stem cell, microRNA, and nanoparticle-based treatments that could positively impact spinal cord injury management. Finally, future perspectives and challenges are also highlighted based on the ongoing clinical trials related to medications targeting microglia.

Passive Anti-Amyloid Beta Immunotherapies in Alzheimer's Disease: From Mechanisms to Therapeutic Impact.

Alzheimer's disease, the most common type of dementia worldwide, lacks effective disease-modifying therapies despite significant research efforts. Passive anti-amyloid immunotherapies represent a promising avenue for Alzheimer's disease treatment by targeting the amyloid-beta peptide, a key pathological hallmark of the disease. This approach utilizes monoclonal antibodies designed to specifically bind amyloid beta, facilitating its clearance from the brain. This review offers an original and critical analysis of anti-amyloid immunotherapies by exploring several aspects. Firstly, the mechanisms of action of these therapies are reviewed, focusing on their ability to promote Aß degradation and enhance its efflux from the central nervous system. Subsequently, the extensive history of clinical trials involving anti-amyloid antibodies is presented, from initial efforts using first-generation molecules leading to mixed results to recent clinically approved drugs. Along with undeniable progress, the authors also highlight the pitfalls of this approach to offer a balanced perspective on this topic. Finally, based on its potential and limitations, the future directions of this promising therapeutic strategy for Alzheimer's disease are emphasized.

Electrophysiological signatures of veridical head direction in humans.

Information about heading direction is critical for navigation as it provides the means to orient ourselves in space. However, given that veridical head-direction signals require physical rotation of the head and most human neuroimaging experiments depend upon fixing the head in position, little is known about how the human brain is tuned to such heading signals. Here we adress this by asking 52 healthy participants undergoing simultaneous electroencephalography and motion tracking recordings (split into two experiments) and 10 patients undergoing simultaneous intracranial electroencephalography and motion tracking recordings to complete a series of orientation tasks in which they made physical head rotations to target positions. We then used a series of forward encoding models and linear mixed-effects models to isolate electrophysiological activity that was specifically tuned to heading direction. We identified a robust posterior central signature that predicts changes in veridical head orientation after regressing out confounds including sensory input and muscular activity. Both source localization and intracranial analysis implicated the medial temporal lobe as the origin of this effect. Subsequent analyses disentangled head-direction signatures from signals relating to head rotation and those reflecting location-specific effects. Lastly, when directly comparing head direction and eye-gaze-related tuning, we found that the brain maintains both codes while actively navigating, with stronger tuning to head direction in the medial temporal lobe. Together, these results reveal a taxonomy of population-level head-direction signals within the human brain that is reminiscent of those reported in the single units of rodents.

Spindle-locked ripples mediate memory reactivation during human NREM sleep.

Memory consolidation relies in part on the reactivation of previous experiences during sleep. The precise interplay of sleep-related oscillations (slow oscillations, spindles and ripples) is thought to coordinate the information flow between relevant brain areas, with ripples mediating memory reactivation. However, in humans empirical evidence for a role of ripples in memory reactivation is lacking. Here, we investigated the relevance of sleep oscillations and specifically ripples for memory reactivation during human sleep using targeted memory reactivation. Intracranial electrophysiology in epilepsy patients and scalp EEG in healthy participants revealed that elevated levels of slow oscillation - spindle activity coincided with the read-out of experimentally induced memory reactivation. Importantly, spindle-locked ripples recorded intracranially from the medial temporal lobe were found to be correlated with the identification of memory reactivation during non-rapid eye movement sleep. Our findings establish ripples as key-oscillation for sleep-related memory reactivation in humans and emphasize the importance of the coordinated interplay of the cardinal sleep oscillations.

Antibody-mediated autoimmunity in symptom-based disorders: position statement and proceedings from an international workshop.

A 2-day closed workshop was held in Liverpool, United Kingdom, to discuss the results of research concerning symptom-based disorders (SBDs) caused by autoantibodies, share technical knowledge, and consider future plans. Twenty-two speakers and 14 additional participants attended. This workshop set out to consolidate knowledge about the contribution of autoantibodies to SBDs. Persuasive evidence for a causative role of autoantibodies in disease often derives from experimental "passive transfer" approaches, as first established in neurological research. Here, serum immunoglobulin (IgM or IgG) is purified from donated blood and transferred to rodents, either systemically or intrathecally. Rodents are then assessed for the expression of phenotypes resembling the human condition; successful phenotype transfer is considered supportive of or proof for autoimmune pathology. Workshop participants discussed passive transfer models and wider evidence for autoantibody contribution to a range of SBDs. Clinical trials testing autoantibody reduction were presented. Cornerstones of both experimental approaches and clinical trial parameters in this field were distilled and presented in this article. Mounting evidence suggests that immunoglobulin transfer from patient donors often induces the respective SBD phenotype in rodents. Understanding antibody binding epitopes and downstream mechanisms will require substantial research efforts, but treatments to reduce antibody titres can already now be evaluated.

Iron chelators as a therapeutic option for Alzheimer's disease-A mini-review.

Neurodegenerative disorders, particularly Alzheimer's disease (AD), remain a great challenge regarding the finding of effective treatment, one main reason being the incomplete understanding of their etiology. With many intensely debated hypotheses, a newer approach based on the impact of iron imbalance in sustaining neurodegeneration in the central nervous system becomes increasingly popular. Altered iron homeostasis leads to increased iron accumulation in specific brain areas, explaining the clinical picture of AD patients. Moreover, growing evidence sustains the significant impact of iron metabolism in relationship to other pathological processes encountered in the AD-affected brain, such as the amyloidogenic pathway, chronic inflammation, or oxidative stress. In this context, this mini-review aims to summarize the novel data from the continuously expanding literature on this topic in a didactic manner. Thus, in the first part, the authors briefly highlight the most relevant aspects related to iron absorption, transport, regulation, and elimination at the cerebral level, focusing on the role of the blood-brain barrier and the newer concept of ferroptosis. Subsequently, currently available iron chelation therapies are discussed, including an overview of the most relevant clinical trials on this topic. In the final part, based on the latest results from in vitro and in vivo studies, new research directions are suggested to enhance the development of effective antidementia therapies.

Respiration modulates sleep oscillations and memory reactivation in humans.

The beneficial effect of sleep on memory consolidation relies on the precise interplay of slow oscillations and spindles. However, whether these rhythms are orchestrated by an underlying pacemaker has remained elusive. Here, we tested the relationship between respiration, which has been shown to impact brain rhythms and cognition during wake, sleep-related oscillations and memory reactivation in humans. We re-analysed an existing dataset, where scalp electroencephalography and respiration were recorded throughout an experiment in which participants (N = 20) acquired associative memories before taking a nap. Our results reveal that respiration modulates the emergence of sleep oscillations. Specifically, slow oscillations, spindles as well as their interplay (i.e., slow-oscillation_spindle complexes) systematically increase towards inhalation peaks. Moreover, the strength of respiration - slow-oscillation_spindle coupling is linked to the extent of memory reactivation (i.e., classifier evidence in favour of the previously learned stimulus category) during slow-oscillation_spindles. Our results identify a clear association between respiration and memory consolidation in humans and highlight the role of brain-body interactions during sleep.

The Roles of the Amyloid Beta Monomers in Physiological and Pathological Conditions.

Amyloid beta peptide is an important biomarker in Alzheimer's disease, with the amyloidogenic hypothesis as one of the central hypotheses trying to explain this type of dementia. Despite numerous studies, the etiology of Alzheimer's disease remains incompletely known, as the pathological accumulation of amyloid beta aggregates cannot fully explain the complex clinical picture of the disease. Or, for the development of effective therapies, it is mandatory to understand the roles of amyloid beta at the brain level, from its initial monomeric stage prior to aggregation in the form of senile plaques. In this sense, this review aims to bring new, clinically relevant data on a subject intensely debated in the literature in the last years. In the first part, the amyloidogenic cascade is reviewed and the possible subtypes of amyloid beta are differentiated. In the second part, the roles played by the amyloid beta monomers in physiological and pathological (neurodegenerative) conditions are illustrated based on the most relevant and recent studies published on this topic. Finally, considering the importance of amyloid beta monomers in the pathophysiology of Alzheimer's disease, new research directions with diagnostic and therapeutic impacts are suggested.

SARS-CoV-2 Possible Etiology of Cerebral Venous Thrombosis in a Teenager: Case Report and Review of Literature.

Cerebral venous thrombosis in pediatric patient has a varied etiology. The authors present the case of a teenager who, since the debut of SARS-CoV-2 infection, has accused intermittent right side hemicrania, which has become persistent in association with nausea and vomiting since the 5th day of quarantine. She was hospitalized in the 9th day since the debut. Neuroimaging revealed extended venous cerebral thrombosis affecting the right sigmoid sinus, the transverse sinus bilaterally, the confluence of the transverse sinuses and the right internal jugular vein. The evolution was favorable under anticoagulant and symptomatic treatment. Laboratory tests excluded other etiological causes for the cerebral venous thrombosis, thus the authors consider that cerebral thrombosis is a possible complication of SARS-CoV-2 infection in teenagers.

Intrathecal Pseudodelivery of Drugs in the Therapy of Neurodegenerative Diseases: Rationale, Basis and Potential Applications.

Intrathecal pseudodelivery of drugs is a novel route to administer medications to treat neurodegenerative diseases based on the CSF-sink therapeutic strategy by means of implantable devices. While the development of this therapy is still in the preclinical stage, it offers promising advantages over traditional routes of drug delivery. In this paper, we describe the rationale of this system and provide a technical report on the mechanism of action, that relies on the use of nanoporous membranes enabling selective molecular permeability. On one side, the membranes do not permit the crossing of certain drugs; whereas, on the other side, they permit the crossing of target molecules present in the CSF. Target molecules, by binding drugs inside the system, are retained or cleaved and subsequently eliminated from the central nervous system. Finally, we provide a list of potential indications, the respective molecular targets, and the proposed therapeutic agents.

A Nanostructured Protein Filtration Device for Possible Use in the Treatment of Alzheimer's Disease-Concept and Feasibility after In Vivo Tests.

BACKGROUND: Alzheimer's disease (AD), along with other neurodegenerative disorders, remains a challenge for clinicians, mainly because of the incomplete knowledge surrounding its etiology and inefficient therapeutic options. Considering the central role of amyloid beta (Aß) in the onset and evolution of AD, Aß-targeted therapies are among the most promising research directions. In the context of decreased Aß elimination from the central nervous system in the AD patient, the authors propose a novel therapeutic approach based on the "Cerebrospinal Fluid Sink Therapeutic Strategy" presented in previous works. This article aims to demonstrate the laborious process of the development and testing of an effective nanoporous ceramic filter, which is the main component of an experimental device capable of filtrating Aß from the cerebrospinal fluid in an AD mouse model. METHODS: First, the authors present the main steps needed to create a functional filtrating nanoporous ceramic filter, which represents the central part of the experimental filtration device. This process included synthesis, functionalization, and quality control of the functionalization, which were performed via various spectroscopy methods and thermal analysis, selectivity measurements, and a biocompatibility assessment. Subsequently, the prototype was implanted in APP/PS1 mice for four weeks, then removed, and the nanoporous ceramic filter was tested for its filtration capacity and potential structural damages. RESULTS: In applying the multi-step protocol, the authors developed a functional Aß-selective filtration nanoporous ceramic filter that was used within the prototype. All animal models survived the implantation procedure and had no significant adverse effects during the 4-week trial period. Post-treatment analysis of the nanoporous ceramic filter showed significant protein loading, but no complete clogging of the pores. CONCLUSIONS: We demonstrated that a nanoporous ceramic filter-based system that filtrates Aß from the cerebrospinal fluid is a feasible and safe treatment modality in the AD mouse model. The presented prototype has a functional lifespan of around four weeks, highlighting the need to develop advanced nanoporous ceramic filters with anti-biofouling properties to ensure the long-term action of this therapy.