A potential therapeutic strategy based on acute oxidative stress induction for wild-type NRF2/KEAP1 lung squamous cell carcinoma.

Extensive efforts have been conducted in the search for new targetable drivers of lung squamous cell carcinoma (LUSC); to date, however, candidates remain mostly unsuccessful. One of the oncogenic pathways frequently found to be active in LUSC is NFE2L2 (NRF2 transcription factor), the levels of which are regulated by KEAP1. Mutations in NFE2L2 or KEAP1 trigger NRF2 activation, an essential protector against reactive oxygen species (ROS). We hypothesized that the frequency of NRF2 activation in LUSC (∼35 %) may reflect a sensitivity of LUSC to ROS. Results from this study reveal that whereas tumors containing active forms of NRF2 were protected, ROS induction in wild-type NFE2L2/KEAP1 LUSC cells triggered ferroptosis. The mechanism of ROS action in normal-NRF2 LUSC cells involved transient NRF2 activation, miR-126-3p/miR-126-5p upregulation, and reduction of p85ß and SETD5 levels. SETD5 levels reduction triggered pentose pathway gene levels increase to toxic values. Simultaneous depletion of p85ßPI3K and SETD5 triggered LUSC cell death, while p85ßPI3K and SETD5 overexpression rescued survival of ROS-treated normal-NRF2 LUSC cells. This shows that the cascade involving NRF2 > miR-126-3p, miR-126-5p > p85ßPI3K and SETD5 is responsible for ROS-induced cell death in normal-NRF2 LUSC. Transient ROS-induced cell death is shown in 3D spheroids, patient-derived organoids, and in xenografts of wild-type NFE2L2/KEAP1 LUSC cells, supporting the potential of acute local ROS induction as a therapeutic strategy for LUSC patients with normal-NRF2.

Protocol of a clinical trial on the effectiveness of pudendal nerve block with and without neurostimulation in reducing posthemorroidectomy pain.

INTRODUCTION: Hemorrhoidal pathology is the most frequent proctological problem with a prevalence of 44% of the adult population. The most effective treatment is surgery but it also has the highest postoperative pain rate with moderate to severe pain rates of 30-40% during the first 24-48 hours. Here lies the importance of seeking measures to improve this situation, such as the pudendal nerve block with local anesthetic. However, the variability of the pudendal nerve sometimes makes its blockade ineffective and for this reason nerve location methods are sought to achieve a higher rate of success. The main aim of the study is to compare pain in the immediate postoperative period (24 h) after hemorrhoidectomy in patients with pudendal nerve block guided by anatomical references and guided by neurostimulation. METHODS: The present project proposes the performance of a single-center, triple-blind, randomized clinical trial of efficacy, carried out under conditions of routine clinical practice. Patients over 18 years old with hemorrhoids refractory to medical treatment, symptomatic grade III-IV and grade II hemorrhoids that do not respond to conservative procedures in a third level hospital in Spain and that are subsidiaries of surgery in major ambulatory surgery will be included. Demographic variables, variables on hemorrhoidal pathology, details of surgery, verbal numeric pain scale in the preoperative period and surgical complications will be collected. RESULTS: Not avaliable until the end of the study. CONCLUSIONS: The pudendal nerve block guided by anatomical landmarks has been shown to be useful in postoperative pain control after hemorrhoidectomy although the use of the neurostimulator has not been well studied and we believe it may improve outcom.

Linguistic laws in biology.

Linguistic laws, the common statistical patterns of human language, have been investigated by quantitative linguists for nearly a century. Recently, biologists from a range of disciplines have started to explore the prevalence of these laws beyond language, finding patterns consistent with linguistic laws across multiple levels of biological organisation, from molecular (genomes, genes, and proteins) to organismal (animal behaviour) to ecological (populations and ecosystems). We propose a new conceptual framework for the study of linguistic laws in biology, comprising and integrating distinct levels of analysis, from description to prediction to theory building. Adopting this framework will provide critical new insights into the fundamental rules of organisation underpinning natural systems, unifying linguistic laws and core theory in biology.

Portable determinations for legislated dissolved nitrogen forms in several environmental water samples as a study case.

In this work, we have studied the main species involved in determining total dissolved nitrogen (TDN) in water samples for accommodating a variety of quantitation methodologies to portable instruments and with the goal to achieve in situ analysis. The rise of water eutrophication is becoming an ecological problem in the world and TDN contributes markedly to this. Traditionally the several forms of DN are measured in the laboratory using conventional instrumentation from grab samples, but their analysis in place and in real time is a current demand. Inorganic nitrogen: NO3-, NO2- and NH4+, and organic nitrogen, such as amino nitrogen were tested here. For nitrate that presents native UV absorption suitable for direct water analysis, a portable optical fiber probe was compared with benchtop equipment and an in place analyzer. For nitrate, nitrite and ammonium, in situ solid devices that deliver reagents needed were tested and water color was measured by a smartphone coupled with a miniaturized optical fiber spectrometer and a miniaturized spectrometer or from images obtained and their RGB components. Amino nitrogen of some aromatic aminoacids with native fluorescence was followed by a portable optical fiber probe. Organic amino nitrogen and ammonium were determined by a portable luminometer and luminol supported in a measurement tube. Moreover, a portable miniaturized liquid chromatograph was shown suitable for monitoring priority nitrogen environmental pollutants. All options provided suitable results in comparison with lab estimations and were useful for evaluating if the legislation is fulfilled for the variety of tested waters. A discussion about the several portable options proposed for in place analysis, in function of the legislated determinations needed for each type of water was carried out.

Cabinas, ¿las conoces bien? / Cabinets, do you know them well?

Las cabinas de flujo laminar (CFL) y de seguridad biológica (CSB) son un elemento fundamental en los laboratorios de biología en general y suponen un equipamiento básico en los laboratorios de reproduc-ción humana asistida.Para entender su funcionamiento, debemos conocer algunos conceptos básicos como la clasificación de los agentes biológicos, los niveles de bioseguridad y los filtros HEPA.Esto nos permitirá diferenciar entre los distintos tipos disponibles y el uso al que se destinan cada una de ellas. (AU)

Laminar flow cabinets (LFC) and biological safety cabinets (BSC) are fundamental elements in biology laboratories in general and are basic equipment in assisted human reproduction laboratories.To understand its operation, we must know some basic concepts such as the classification of biological agents, biosafety levels, and HEPA filters.This will allow us to differentiate between the different types available and the use to which each of them is intended (AU)

Gender, loneliness and happiness during COVID-19.

We analyse a measure of loneliness from a representative sample of German individuals interviewed in both 2017 and at the beginning of the COVID-19 pandemic in 2020. Both men and women felt lonelier during the COVID-19 pandemic than they did in 2017. The pandemic more than doubled the gender loneliness gap: women were lonelier than men in 2017, and the 2017-2020 rise in loneliness was far larger for women. This rise is mirrored in life-satisfaction scores. Men's life satisfaction changed only little between 2017 and 2020; yet that of women fell dramatically, and sufficiently so to produce a female penalty in life satisfaction. We estimate that almost all of this female penalty is explained by the disproportionate rise in loneliness for women during the COVID-19 pandemic.

Variable expression of linguistic laws in ape gesture: a case study from chimpanzee sexual solicitation.

Two language laws have been identified as consistent patterns shaping animal behaviour, both acting on the organizational level of communicative systems. Zipf's law of brevity describes a negative relationship between behavioural length and frequency. Menzerath's law defines a negative correlation between the number of behaviours in a sequence and average length of the behaviour composing it. Both laws have been linked with the information-theoretic principle of compression, which tends to minimize code length. We investigated their presence in a case study of male chimpanzee sexual solicitation gesture. We failed to find evidence supporting Zipf's law of brevity, but solicitation gestures followed Menzerath's law: longer sequences had shorter average gesture duration. Our results extend previous findings suggesting gesturing may be limited by individual energetic constraints. However, such patterns may only emerge in sufficiently large datasets. Chimpanzee gestural repertoires do not appear to manifest a consistent principle of compression previously described in many other close-range systems of communication. Importantly, the same signallers and signals were previously shown to adhere to these laws in subsets of the repertoire when used in play; highlighting that, in addition to selection on the signal repertoire, ape gestural expression appears shaped by factors in the immediate socio-ecological context.

Maternidad en el tenis profesional: ¿es suficiente con cambiar la normativa? / Maternidade no tênisprofissional: basta mudar o regulamento? / Motherhood in professional tennis: is it enough just by changingthe rules?

El cambio de normativa de la Women’s Tennis Association (WTA) a principios del 2019 sobre maternidad y el auge de investigaciones en psicología del deporte sobre este tema en el deporte de élite, inspiraron este estudio cuyo objetivo fue explorar si el cambio de normativa modifica la visión de la compaginación de maternidad y carrera tenística en tenistas profesionales en activo y retiradas, madres y no madres. Participaron 10 mujeres tenistas españolas, algunas madres (n = 3) y otras no (n = 7). Para la recolección de datos se utilizó una entrevista semi-estructurada y a partir de un análisis temático del contenido se definieron tres temas: (a) game, set and match: ¿es suficiente solo con cambiar la normativa? (b) Centre court: al servicio mama-tenista versus al resto tenista, y (c) warning coaching: el tenis como deporte de equipo. Los resultados revelan como las modificaciones del reglamento facilitan un primer paso hacia la compatibilización de la maternidad con el tenis de élite, pero aún hacen falta más medidas de acompañamiento como las sugeridas en este estudio: (a) contar con el apoyo del entorno psicosocial de la deportista, (b) disponer de una ayuda económica, (c) disponer de espacios para los hijos en el entorno deportivo y (d) facilitar elementos básicos para los niños en los torneos. (AU)

Changes in the Women’s Tennis Association (WTA) rulebook at the beginning of 2019 regarding the special ranking for pregnancy or parental start and the uprising in sports psychology investigations regarding this theme in elite sport, inspired this study. The aim was to explore whether the changes in the WTA regulations modifies the vision of the possibility to combine motherhood and professional sportscareer. Participants were 10 Spanish female elite tennis players, both current and former players, some mothers (n = 3) and others non-mothers (n = 7). For data collection, a semi-structured interview was used and, through thematic content analysis, three themes were defined: (a) game, set and match: is it enough just by changing the rules? (b) centre court: to serve tennis player and mom vs. at the return tennis player and (c) warning coaching: tennis as a team sport. The interpretation of the results show how motherhood and an elite tennis career is possible to combine even though it is still a feat for the mother athlete. Our study suggests strategies that could favour motherhood with an elite tennis career: (a) have the support from the athletes’ entourage, (b) having financial support or funding, (c) have some areas or rooms destined for children in tournaments,and (d) provide basic services for children in tournaments (AU)

A mudança nos regulamentos da Women's Tennis Association (WTA) no início de 2019 sobre a maternidade e o surgimento das pesquisas em psicologia do esporte sobre o assunto no esporte de elite inspiraram este estudo cujo objetivo foi explorar se a mudança nos regulamentos modifica a visão da combinação de maternidadee carreira esportivaem tenistas profissionais. Participaram 10 tenistas espanholas, ativos e aposentados, algumas mães (n= 3) e outras não (n= 7). Para a coleta de dados, foi utilizada uma entrevista semiestruturada e, a partir da análise temática de conteúdo, foram definidos três temas: (a) jogo, jogo e jogo: basta mudar o regulamento? (b) quadra central: servir a jogadora-mãe contra o resto da jogadora, e (c) orientação de advertência: tênis como esporte de equipe. A interpretação dos resultados mostra como as modificações nas normas facilitam um primeiro passo para compatibilizar a maternidade com o tênis de elite, mas ainda são necessárias medidas de apoio como as sugeridas neste estudo: (a) contar com o apoio do ambiente psicossocial da atleta, (b) ter auxílio financeiro, (c) ter vagas para crianças no ambiente esportivo,e (d) fornecer elementos básicos para as crianças em torneios. (AU)

Plasmonic sensor for hydrogen sulphide in saliva: Multisensor platform and bag format.

In recent years, there is a growing demand for optical sensors given their analytical properties, and the possibility of in situ implementation. Among all the types of optical sensors, plasmonic sensors have aroused great interest in the scientific community. In this work, the ability of a plasmonic sensor based on AgNPs retained on a Nylon surface is studied to determine hydrogen sulfide, which can be an indicator of oral diseases. This compound produces a color change of the sensor from yellow to brown directly related to its concentration. The sensor response is evaluated in two different assay formats such as bag and well microplates. The figures of merits of both methodologies have been obtained and compared. The advantages and disadvantages of the different formats have been shown. Finally, the sensor is applied to quantify sulfides in real saliva. Concentrations ranged from 30 µ L-1 to 600 µ L-1 have been obtained for the voluntaries. Besides that, in this approach the RGB coordinates from images have been used as analytical signal too. The results achieved have demonstrated that the sensor and the methodology applied provide good selectivity, sensibility, rapidity, it is non-invasive and it can be used as indirect method to measure problems in the oral cavity.

Optimality of syntactic dependency distances.

It is often stated that human languages, as other biological systems, are shaped by cost-cutting pressures but, to what extent? Attempts to quantify the degree of optimality of languages by means of an optimality score have been scarce and focused mostly on English. Here we recast the problem of the optimality of the word order of a sentence as an optimization problem on a spatial network where the vertices are words, arcs indicate syntactic dependencies, and the space is defined by the linear order of the words in the sentence. We introduce a score to quantify the cognitive pressure to reduce the distance between linked words in a sentence. The analysis of sentences from 93 languages representing 19 linguistic families reveals that half of languages are optimized to a 70% or more. The score indicates that distances are not significantly reduced in a few languages and confirms two theoretical predictions: that longer sentences are more optimized and that distances are more likely to be longer than expected by chance in short sentences. We present a hierarchical ranking of languages by their degree of optimization. The score has implications for various fields of language research (dependency linguistics, typology, historical linguistics, clinical linguistics, and cognitive science). Finally, the principles behind the design of the score have implications for network science.

Analysis of co-isogenic prion protein deficient mice reveals behavioral deficits, learning impairment, and enhanced hippocampal excitability.

BACKGROUND: Cellular prion protein (PrPC) is a cell surface GPI-anchored protein, usually known for its role in the pathogenesis of human and animal prionopathies. However, increasing knowledge about the participation of PrPC in prion pathogenesis contrasts with puzzling data regarding its natural physiological role. PrPC is expressed in a number of tissues, including at high levels in the nervous system, especially in neurons and glial cells, and while previous studies have established a neuroprotective role, conflicting evidence for a synaptic function has revealed both reduced and enhanced long-term potentiation, and variable observations on memory, learning, and behavior. Such evidence has been confounded by the absence of an appropriate knock-out mouse model to dissect the biological relevance of PrPC, with some functions recently shown to be misattributed to PrPC due to the presence of genetic artifacts in mouse models. Here we elucidate the role of PrPC in the hippocampal circuitry and its related functions, such as learning and memory, using a recently available strictly co-isogenic Prnp0/0 mouse model (PrnpZH3/ZH3). RESULTS: We performed behavioral and operant conditioning tests to evaluate memory and learning capabilities, with results showing decreased motility, impaired operant conditioning learning, and anxiety-related behavior in PrnpZH3/ZH3 animals. We also carried in vivo electrophysiological recordings on CA3-CA1 synapses in living behaving mice and monitored spontaneous neuronal firing and network formation in primary neuronal cultures of PrnpZH3/ZH3 vs wildtype mice. PrPC absence enhanced susceptibility to high-intensity stimulations and kainate-induced seizures. However, long-term potentiation (LTP) was not enhanced in the PrnpZH3/ZH3 hippocampus. In addition, we observed a delay in neuronal maturation and network formation in PrnpZH3/ZH3 cultures. CONCLUSION: Our results demonstrate that PrPC promotes neuronal network formation and connectivity. PrPC mediates synaptic function and protects the synapse from excitotoxic insults. Its deletion may underlie an epileptogenic-susceptible brain that fails to perform highly cognitive-demanding tasks such as associative learning and anxiety-like behaviors.

Mycoplasma genitalium and sexually transmitted infections: evidences and figures in a tertiary hospital.

OBJECTIVE: Mycoplasma genitalium is an emerging cause of sexually transmitted infections (STIs) and has been implicated in non-gonococcal urethritis in men and cervicitis in woman. The aim of this study is determinate the incidence and pathogenicity of M. genitalium within the diagnosis of STIs detected from clinical samples in a third level hospital. METHODS: A total of 8,473 samples from endocervix, urethra, vagina, rectum and others were processed applying Allpex STI Essential Assay. More than 190 records were reviewed to determinate M. genitalium pathogenicity. RESULTS: M. genitalium was detected in a rate 2.8%. Co-infections were detected in 20% of the patients. CONCLUSIONS: M. genitalium is considered a STI emerging pathogen thanks to the renewal of multiplex-PCR tests although with a low incidence in our approach. Emerging from our experience and the institutional recommendations both detection of acid nucleic techniques (NAATs) and gonococcal culture might be implemented accurately and coexist to adequate prescriptions.

Linguistic laws in biology.

Linguistic laws, the common statistical patterns of human language, have been investigated by quantitative linguists for nearly a century. Recently, biologists from a range of disciplines have started to explore the prevalence of these laws beyond language, finding patterns consistent with linguistic laws across multiple levels of biological organisation, from molecular (genomes, genes, and proteins) to organismal (animal behaviour) to ecological (populations and ecosystems). We propose a new conceptual framework for the study of linguistic laws in biology, comprising and integrating distinct levels of analysis, from description to prediction to theory building. Adopting this framework will provide critical new insights into the fundamental rules of organisation underpinning natural systems, unifying linguistic laws and core theory in biology.

Zipf's laws of meaning in Catalan.

In his pioneering research, G. K. Zipf formulated a couple of statistical laws on the relationship between the frequency of a word with its number of meanings: the law of meaning distribution, relating the frequency of a word and its frequency rank, and the meaning-frequency law, relating the frequency of a word with its number of meanings. Although these laws were formulated more than half a century ago, they have been only investigated in a few languages. Here we present the first study of these laws in Catalan. We verify these laws in Catalan via the relationship among their exponents and that of the rank-frequency law. We present a new protocol for the analysis of these Zipfian laws that can be extended to other languages. We report the first evidence of two marked regimes for these laws in written language and speech, paralleling the two regimes in Zipf's rank-frequency law in large multi-author corpora discovered in early 2000s. Finally, the implications of these two regimes will be discussed.

Cadaverine and Spermine Elicit Ca2+ Uptake in Human CP Cells via a Trace Amine-Associated Receptor 1 Dependent Pathway.

The choroid plexus (CP) constitutes a barrier between the blood and the cerebrospinal fluid (CSF) which regulates the exchange of substances between these two fluids through mechanisms that are not completely understood. Polyamines as spermine, spermidine and putrescine are produced by all cells and are present in the CSF. Interestingly, their levels are altered in some neuronal disorders as Alzheimer's and Parkinson's diseases, thus increasing the interest in their signalling in the central nervous system (CNS). Cadaverine, on the other hand, is synthetized by the intestinal microbiome, suggesting that the presence of this bacterial metabolite in the CSF requires that it is up taken to the CNS across brain barriers. We knew that polyamines are detected by the olfactory signalling cascade operating at the CP, but the receptor involved had not been identified. The zebrafish TAAR13c was the only receptor known to bind a polyamine-cadaverine. Thus, we searched for a human receptor with homology to TAAR13c and found that some human TAARs including TAAR1 showed great homology. Then, we confirmed the expression of TAAR1 mRNA and protein in a human cell line of the CP, and in human CP samples. Calcium imaging assays after TAAR1 knockdown in these cells with a specific siRNA against TAAR1 showed a consistent reduction in the responses of these cells to cadaverine and spermidine, but not to spermine, suggesting that TAAR1 is activated by cadaverine and spermidine, but not spermine.

Distinct flavors of Zipf's law and its maximum likelihood fitting: Rank-size and size-distribution representations.

In recent years, researchers have realized the difficulties of fitting power-law distributions properly. These difficulties are higher in Zipfian systems, due to the discreteness of the variables and to the existence of two representations for these systems, i.e., two versions depending on the random variable to fit: rank or size. The discreteness implies that a power law in one of the representations is not a power law in the other, and vice versa. We generate synthetic power laws in both representations and apply a state-of-the-art fitting method to each of the two random variables. The method (based on maximum likelihood plus a goodness-of-fit test) does not fit the whole distribution but the tail, understood as the part of a distribution above a cutoff that separates non-power-law behavior from power-law behavior. We find that, no matter which random variable is power-law distributed, using the rank as the random variable is problematic for fitting, in general (although it may work in some limit cases). One of the difficulties comes from recovering the "hidden" true ranks from the empirical ranks. On the contrary, the representation in terms of the distribution of sizes allows one to recover the true exponent (with some small bias when the underlying size distribution is a power law only asymptotically).

Community-based Health Data Cooperatives Towards Improving the Immigrant Community Health: A Scoping Review to Inform Policy and Practice.

BACKGROUND: In the case of immigrant health and wellness, data are the key limiting factor, where comprehensive national knowledge on immigrant health and health service utilisation is limited. New data and data silos are an inherent response to the increase in technology in the collection and storage of data. The Health Data Cooperative (HDC) model allows members to contribute, store, and manage their health-related information, and members are the rightful data owners and decision-makers to data sharing (e g. research communities, commercial entities, government bodies). OBJECTIVE: This review attempts to scope the literature on HDC and fulfill the following objectives: 1) identify and describe the type of literature that is available on the HDC model; 2) describe the key themes related to HDCs; and 3) describe the benefits and challenges related to the HDC model. METHODS: We conducted a scoping review using the five-stage framework outlined by Arskey and O'Malley to systematically map literature on HDCs using two search streams: 1) a database and grey literature search; and 2) an internet search. We included all English records that discussed health data cooperative and related key terms. We used a thematic analysis to collate information into comprehensive themes. RESULTS: Through a comprehensive screening process, we found 22 database and grey literature records, and 13 Internet search records. Three major themes that are important to stakeholders include data ownership, data security, and data flow and infrastructure. CONCLUSIONS: The results of this study are an informative first step to the study of the HDC model, or an establishment of a HDC in immigrant communities. KEY WORDS: community health, health data, cooperative, and citizen data empowermen.

White matter alterations in Alzheimer's disease without concomitant pathologies.

AIMS: Most individuals with AD neuropathological changes have co-morbidities which have an impact on the integrity of the WM. This study analyses oligodendrocyte and myelin markers in the frontal WM in a series of AD cases without clinical or pathological co-morbidities. METHODS: From a consecutive autopsy series, 206 cases had neuropathological changes of AD; among them, only 33 were AD without co-morbidities. WM alterations were first evaluated in coronal sections of the frontal lobe in every case. Then, RT-qPCR and immunohistochemistry were carried out in the frontal WM of AD cases without co-morbidities to analyse the expression of selected oligodendrocyte and myelin markers. RESULTS: WM demyelination was more marked in AD with co-morbidities when compared with AD cases without co-morbidities. Regarding the later, mRNA expression levels of MBP, PLP1, CNP, MAG, MAL, MOG and MOBP were preserved at stages I-II/0-A when compared with middle-aged (MA) individuals, but significantly decreased at stages III-IV/0-C. This was accompanied by reduced expression of NG2 and PDGFRA mRNA, reduced numbers of NG2-, Olig2- and HDAC2-immunoreactive cells and reduced glucose transporter immunoreactivity. Partial recovery of some of these markers occurred at stages V-VI/B-C. CONCLUSIONS: The present observations demonstrate that co-morbidities have an impact on WM integrity in the elderly and in AD, and that early alterations in oligodendrocytes and transcription of genes linked to myelin proteins in WM occur in AD cases without co-morbidities. These are followed by partial recovery attempts at advanced stages. These observations suggest that oligodendrocytopathy is part of AD.

Plasma total prion protein as a potential biomarker for neurodegenerative dementia: diagnostic accuracy in the spectrum of prion diseases.

AIMS: In the search for blood-based biomarkers of neurodegenerative diseases, we characterized the concentration of total prion protein (t-PrP) in the plasma of neurodegenerative dementias. We aimed to assess its accuracy in this differential diagnostic context. METHODS: Plasma t-PrP was measured in 520 individuals including healthy controls (HC) and patients diagnosed with neurological disease control (ND), Alzheimer's disease (AD), sporadic Creutzfeldt-Jakob disease (sCJD), frontotemporal dementia (FTD), Lewy body dementia (LBD) and vascular dementia (VaD). Additionally, t-PrP was quantified in genetic prion diseases and iatrogenic CJD. The accuracy of t-PrP discriminating the diagnostic groups was evaluated and correlated with demographic, genetic and clinical data in prion diseases. Markers of blood-brain barrier impairment were investigated in sCJD brains. RESULTS: Compared to HC and ND, elevated plasma t-PrP concentrations were detected in sCJD, followed by FTD, AD, VaD and LBD. In sCJD, t-PrP was associated neither with age nor sex, but with codon 129 PRNP genotype. Plasma t-PrP concentrations correlated with cerebrospinal fluid (CSF) markers of neuro-axonal damage, but not with CSF t-PrP. In genetic prion diseases, plasma t-PrP was elevated in all type of mutations investigated. In sCJD brain tissue, extravasation of immunoglobulin G and the presence of swollen astrocytic end-feet around the vessels suggested leakage of blood-brain barrier as a potential source of increased plasma t-PrP. CONCLUSIONS: Plasma t-PrP is elevated in prion diseases regardless of aetiology. This pilot study opens the possibility to consider plasma t-PrP as a promising blood-based biomarker in the diagnostic of prion disease.