Cost-effectiveness of Alzheimer's disease CSF biomarkers and amyloid-PET in early-onset cognitive impairment diagnosis

This study aimed at determining the cost-effectiveness of amyloid-positron emission tomography (PET) compared to Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers (amyloid-?42, total-Tau and phosphorylated-Tau) for the diagnosis of AD in patients with early-onset cognitive impairment. A decision tree model using a national health care perspective was developed to compare the costs and effectiveness associated with Amyloid-PET and AD CSF biomarkers. Available evidence from the literature and primary data from Hospital Clínic de Barcelona were used to inform the model and calculate the efficiency of these diagnostic alternatives. Medical visits and diagnostic procedures were considered and reported in €2020. We calculated the incremental cost-effectiveness ratio to measure the cost per % of correct diagnoses detected and we perform one-way deterministic and probabilistic sensitivity analyses to assess the uncertainty of these results. Compared with AD CSF biomarkers, Amyloid-PET resulted in 7.40% more correctly diagnosed cases of AD, with an incremental total mean cost of €146,854.80 per 100 cases. We found a 50% of probability that Amyloid-PET was cost-effective for a willingness to pay (WTP) of €19,840.39 per correct case detected. Using a WTP of €75,000, the probability that it is cost-effective reached a maximum of 76.9%, thus leading to a conclusion that Amyloid-PET is not a cost-effective technique compared to AD CSF biomarkers, unless the funder is willing to pay a minimum of €19,840.39 to detect one more correct case. Furthermore, obtaining CSF provides simultaneous information on amyloid ? and tau biomarkers and allows other biomarkers to be analyzed at a relatively low cost.© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany

Capsule growth in Cryptococcus neoformans is coordinated with cell cycle progression

UNLABELLED: The fungal pathogen Cryptococcus neoformans has several virulence factors, among which the most important is a polysaccharide capsule. The size of the capsule is variable and can increase significantly during infection. In this work, we investigated the relationship between capsular enlargement and the cell cycle. Capsule growth occurred primarily during the G1 phase. Real-time visualization of capsule growth demonstrated that this process occurred before the appearance of the bud and that capsule growth arrested during budding. Benomyl, which arrests the cells in G2/M, inhibited capsule growth, while sirolimus (rapamycin) addition, which induces G1 arrest, resulted in cells with larger capsule. Furthermore, we have characterized a mutant strain that lacks a putative G1/S cyclin. This mutant showed an increased capacity to enlarge the capsule, both in vivo (using Galleria mellonella as the host model) and in vitro. In the absence of Cln1, there was a significant increase in the production of extracellular vesicles. Proteomic assays suggest that in the cln1 mutant strain, there is an upregulation of the glyoxylate acid cycle. Besides, this cyclin mutant is avirulent at 37°C, which correlates with growth defects at this temperature in rich medium. In addition, the cln1 mutant showed lower intracellular replication rates in murine macrophages. We conclude that cell cycle regulatory elements are involved in the modulation of the expression of the main virulence factor in C. neoformans. IMPORTANCE: Cryptococcus neoformans is a pathogenic fungus that has significant incidence worldwide. Its main virulence factor is a polysaccharide capsule that can increase in size during infection. In this work, we demonstrate that this process occurs in a specific phase of the cell cycle, in particular, in G1. In agreement, mutants that have an abnormal longer G1 phase show larger capsule sizes. We believe that our findings are relevant because they provide a link between capsule growth, cell cycle progression, and virulence in C. neoformans that reveals new aspects about the pathogenicity of this fungus. Moreover, our findings indicate that cell cycle elements could be used as antifungal targets in C. neoformans by affecting both the growth of the cells and the expression of the main virulence factor of this pathogenic yeast.O.Z. is funded by grants SAF2008-03761 and SAF2011-25140 from the Spanish Ministry for Economics and Competitivity. R.G.-R. is supported by an FPI fellowship (reference BES-2009-015913) from the Spanish Ministry of Science and Innovation. N.T.-C. is supported by an FPI fellowship (reference BES-2012-051837) from the Spanish Ministry for Economics and Competitivity. A.C. is supported by NIH grants HL059842-3, A1033774, A1052733, and AI033142. R.J.B.C. is supported by T32 AI07506 (NIH/NIAID).S

Classifying Alzheimer's disease and frontotemporal dementia using machine learning with cross-sectional and longitudinal magnetic resonance imaging data

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are common causes of dementia with partly overlapping, symptoms and brain signatures. There is a need to establish an accurate diagnosis and to obtain markers for disease tracking. We combined unsupervised and supervised machine learning to discriminate between AD and FTD using brain magnetic resonance imaging (MRI). We included baseline 3T-T1 MRI data from 339 subjects: 99 healthy controls (CTR), 153 AD and 87 FTD patients; and 2-year follow-up data from 114 subjects. We obtained subcortical gray matter volumes and cortical thickness measures using FreeSurfer. We used dimensionality reduction to obtain a single feature that was later used in a support vector machine for classification. Discrimination patterns were obtained with the contribution of each region to the single feature. Our algorithm differentiated CTR versus AD and CTR versus FTD at the cross-sectional level with 83.3% and 82.1% of accuracy. These increased up to 90.0% and 88.0% with longitudinal data. When we studied the classification between AD versus FTD we obtained an accuracy of 63.3% at the cross-sectional level and 75.0% for longitudinal data. The AD versus FTD versus CTR classification has reached an accuracy of 60.7%, and 71.3% for cross-sectional and longitudinal data respectively. Disease discrimination brain maps are in concordance with previous results obtained with classical approaches. By using a single feature, we were capable to classify CTR, AD, and FTD with good accuracy, considering the inherent overlap between diseases. Importantly, the algorithm can be used with cross-sectional and longitudinal data.© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC

Spatio-temporal variation in the composition of the macroalgae assemblage of the intertidal rocky zone from maitencillo, valparaíso, central coast of Chile

Indexación: Scopus.Records on the diversity of algae serve as a foundation for establishing management and environmental protection programs, as well as for determining new commercial uses of algae. With this context in mind, the goal of the present study was to determine the richness, coverage, and composition of the macroalgae assemblage in the intertidal zone of Maitencillo, Valparaíso, Chile over the course of 3 years (2013-2015). A total of 29 species were recorded from 3 phyla - 23 Rhodophyta; 3 Ochrophyta, of the Phaeophyceae class; and 3 Chlorophyta. Species richness presented high spatial and temporal variations, with these variations most significantly explained by intertidal zone (61%) and the seasons (31%). The highest levels of specific richness were recorded in the mid and lower intertidal zones (14 species) in spring, as well as in the lower intertidal zone (14 species) during summer. The lowest values of specific richness were recorded for the mid intertidal zone (2 species) during fall. The distinct levels of the intertidal zone also notably impacted algae assemblage, explaining 53% of variation while the seasons explained 18% of variation. The greatest coverage was recorded in the mid intertidal zone during spring, with a predominance of Mazzaella laminarioides and Ulva spp. complex. In turn, the lowest coverage was found in fall, linked with processes of sand accretion. In rocky walls, the Pyropia complex dominated. Results indicate a marked pattern of vertical and seasonal distribution in the macroalgae assemblage, as well as notably high presence of Rhodophyta species. This benthic flora description serves to update information on the diversity of representative algal species from Valparaíso Region of Chile. © 2018, Universidad de Valparaiso. All rights reserved

Draft genome sequence of chloride-tolerant Leptospirillum ferriphilum Sp-Cl from industrial bioleaching operations in northern Chile

Indexación: Web of Science; PubMedLeptospirillum ferriphilum Sp-Cl is a Gram negative, thermotolerant, curved, rod- shaped bacterium, isolated from an industrial bioleaching operation in northern Chile, where chalcocite is the major copper mineral and copper hydroxychloride atacamite is present in variable proportions in the ore. This strain has unique features as compared to the other members of the species, namely resistance to elevated concentrations of chloride, sulfate and metals. Basic microbiological features and genomic properties of this biotechnologically relevant strain are described in this work. The 2,475,669 bp draft genome is arranged into 74 scaffolds of 74 contigs. A total of 48 RNA genes and 2,834 protein coding genes were predicted from its annotation; 55 % of these were assigned a putative function. Release of the genome sequence of this strain will provide further understanding of the mechanisms used by acidophilic bacteria to endure high osmotic stress and high chloride levels and of the role of chloride-tolerant iron-oxidizers in industrial bioleaching operations.https://standardsingenomics.biomedcentral.com/articles/10.1186/s40793-016-0142-

Impact of Resistance to Fluconazole on Virulence and Morphological Aspects of Cryptococcus neoformans and Cryptococcus gattii Isolates

Cryptococcus spp. are responsible for around one million cases of meningitis every year. Fluconazole (FLU) is commonly used in the treatment of cryptococcosis, mainly in immunocompromised patients and the resistance is usually reported after long periods of treatment. In this study, the morphological characterization and virulence profile of FLU-susceptible and FLU-resistant clinical and environmental isolates of C. neoformans and C. gattii were performed both in vitro and in vivo using the Galleria mellonella model. FLU-susceptible isolates from C. neoformans were significantly more virulent than the FLU-resistant isolates. FLU-susceptible C. gattii isolates showed a different virulence profile from C. neoformans isolates where only the environmental isolate, CL, was more virulent compared with the resistant isolates. Cell morphology and capsule size were analyzed and the FLU-resistant isolates did not change significantly compared with the most sensitive isolates. Growth at 37°C was also evaluated and in both species, the resistant isolates showed a reduced growth at this temperature, indicating that FLU resistance can affect their growth. Based on the results obtained is possible suggest that FLU resistance can influence the morphology of the isolates and consequently changed the virulence profiles. The most evident results were observed for C. neoformans showing that the adaptation of isolates to antifungal selective pressure influenced the loss of virulence

Compliance with current dietary recommendations and geographical variability of diet in women participating in 7 screening programs for breast cancer in Spain

Introducción: Una dieta saludable es especialmente importante durante la menopausia, periodo en el que aumenta el riesgo de varios problemas de salud. Analizamos la dieta de mujeres peri y postmenopáusicas españolas y el grado de cumplimiento de las recomendaciones actuales. Material y métodos: Estudio transversal en 3.574 mujeres de 45-68 años que acuden al cribado de cáncer de mama en 7 centros (A Coruña, Barcelona, Burgos, Palma de Mallorca, Pamplona, Valencia y Zaragoza). Se recogió la dieta mediante un cuestionario de frecuencia de alimentos validado para población española. Para la valoración del cumplimiento de las recomendaciones actuales se utilizaron los rangos recomendados por la Sociedad Española de Nutrición Comunitaria para ingesta de grupos de alimentos y las Ingestas Diarias Recomendadas (IDR) para energía, vitaminas y minerales de la Federación Española de Nutrición, Alimentación y Dietética. Resultados: El 29% de las mujeres eran obesas y un 42% tenía sobrepeso. El aporte calórico medio fue de 2.053 kcal (DE: 480). El perfil calórico general fue de: 43% de la energía aportada por lo carbohidratos, 36% por las grasas, 20% por las proteínas. Se evidenció una ingesta deficiente de vitamina D en todos los nodos del estudio, con una ingesta media general de 2,14 μg/día. Se detectó a su vez una ingesta deficitaria de vitamina E en A Coruña y Burgos. Todos los centros presentaron una ingesta elevada de productos lácteos y de legumbres. El consumo de frutas y verduras fue muy heterogéneo siendo especialmente elevada su ingesta en Mallorca y Valencia mientras que fue baja para ambos grupos de alimentos en A Coruña. La ingesta de aceite de oliva fue elevada en todos los centros exceptuando Burgos con un 74,3% de las mujeres estudiadas por debajo de las 3 raciones al día recomendadas. Conclusiones: Una dieta con menos grasas y proteínas y más rica en vegetales, frutos secos y alimentos ricos en hidratos de carbono equilibraría el balance energético y mejoraría la calidad de la dieta corrigiendo las bajas ingestas de vitaminas D y E. Estas recomendaciones son especialmente importantes en las ciudades más alejadas de la costa mediterránea donde se han detectado mayores incumplimientos de las recomendaciones vigentes y una dieta más alejada de la dieta mediterránea.Introduction: A healthy diet is especially important during menopause, a period which increases the risk of various health problems. We analyzed the diet of periand postmenopausal Spanish women and the degree of compliance with current recommendations. Material and methods: We studied 3574 women 45-68 years old who attended breast cancer screening programmes in 7 centres (A Coruña, Barcelona, Burgos, Palma de Mallorca, Pamplona, Valencia and Zaragoza). Diet information was collected using a food frequency questionnaire validated for the Spanish population. For the assessment of compliance with current guidelines we used the recommendations by the Spanish Society of Community Nutrition for food groups intake and by the Spanish Federation of Nutrition, Food and Dietetics for energy, vitamins and minerals intake. Results: The 29% of women were obese and 42% overweight. The average caloric intake was 2.053 kcal (SD 480). The general energy profile was: 43% of the energy from the carbohydrates, 36% from fats, and 20% from proteins. There was a low vitamin D intake in all centres of the study, with an overall mean intake of 2.14 mg/day. A deficit of vitamin E intake in A Coruña and Burgos was also detected. Intake of dairy products and vegetables was high in all the study centers. The consumption of fruits and vegetables was very heterogeneous, with high intakes observed in Mallorca and Valencia and low for both food groups in A Coruña. The olive oil intake was high in all centers except Burgos with 74.3% of the women studied below the recommended 3 servings per day. Conclusions: A diet with less fat and protein and a higher consumption of vegetables, nuts and foods rich in carbohydrate might balance the energy intake and improve the quality of the diet correcting the low intakes of vitamins D and E. These recommendations are especially important in cities far from the Mediterranean coast where more breaches have been detected over the current recommendations with a lower adherence to the Mediterranean diet.Este estudio ha recibido financiación del Fondo de Investigación Sanitaria (proyecto PI060386) y de Astra-Zéneca (convenio de colaboración entre Astra- Zeneca y el Instituto de salud Carlos III 1306-1306 EPY

Filosofía ambiental de campo: Educación e investigación para la valoración ecológica y ética de los insectos dulceacuícolas (Field environmental philosophy: education and research for the ecological and ethical appreciation of freshwater insects)

In a rapidly changing world, to confront biodiversity losses and the lack of appreciation for and knowledge about the most diverse groups of organisms, it is urgently necessary to stimulate cultural shifts that transcend purely scientific and technological domains. This paper addresses this problem by focusing on one of the least known groups of organisms, and in one of the most remote regions of the planet: freshwater insects in the sub-Antarctic Magellanic ecoregion. The work of this thesis included scientific-ecological and environmental philosophical research that was integrated into formal and non-formal environmental education practices that value freshwater insects, particularly as indicators of climate change. The integration of science and philosophy was done adapting the Field Environmental Philosophy methodology that includes a four-step cycle. Transdisciplinary research on freshwater insects and their sub-Antarctic ecosystems served as a basis for the composition of metaphors and educational activities with schoolchildren, other members of the local community and visitors to Omora Park, in Puerto Williams, Chile. Based on this work, new outdoor educational activities were designed with the objective of awakening the interest of citizens for insects, and nurturing their perceptions about these organisms, their habitats and life habits. In this way, at a local scale this work aims to contribute to greater knowledge, appreciation and conservation of this unique sub-Antarctic biodiversity, and at a global scale it aims to contribute overcoming the under-appreciation for the most diverse group of organisms: the insects

Studying the influence of livestock pressure on gully erosion in rangelands of SW Spain by means of the UAV+SfM workflow

Gully erosion in agrosilvopastoral systems of SW Spain represents a common degradation process, but has been hardly analysed. The suitability of using the Unmanned Aerial Vehicles (UAV) and Structure from Motion photogrammetry (SfM) workflow to map small valley-bottom gullies in these landscapes was tested. The results showed centimetre-level accuracy. Observed strengths and limitations of the UAV+SfM workflow in the study areas are discussed. The resulting cartography allowed mapping soil erosion forms at outstanding spatial scales. All study areas showed evidences of degradation