Prion diseases are a group of rapidly progressing neurodegenerative disorders caused by the misfolding of the endogenous prion protein (PrP
) into a pathogenic form (PrP
). This process, despite ...being the central event underlying these disorders, remains largely unknown at a molecular level, precluding the prediction of new potential outbreaks or interspecies transmission incidents. In this work, we present a method to generate bona fide recombinant prions de novo, allowing a comprehensive analysis of protein misfolding across a wide range of prion proteins from mammalian species. We study more than 380 different prion proteins from mammals and classify them according to their spontaneous misfolding propensity and their conformational variability. This study aims to address fundamental questions in the prion research field such as defining infectivity determinants, interspecies transmission barriers or the structural influence of specific amino acids and provide invaluable information for future diagnosis and therapy applications.
17β-estradiol (E2) may interfere with endocrine, metabolic, and gender-differentiated functions in liver in both females and males. Indirect mechanisms play a crucial role because of the E2 influence ...on the pituitary GH secretion and the GHR-JAK2-STAT5 signaling pathway in the target tissues. E2, through its interaction with the estrogen receptor, exerts direct effects on liver. Hypothyroidism also affects endocrine and metabolic functions of the liver, rendering a metabolic phenotype with features that mimic deficiencies in E2 or GH. In this work, we combined the lipid and transcriptomic analysis to obtain comprehensive information on the molecular mechanisms of E2 effects, alone and in combination with GH, to regulate liver functions in males. We used the adult hypothyroid-orchidectomized rat model to minimize the influence of internal hormones on E2 treatment and to explore its role in male-differentiated functions. E2 influenced genes involved in metabolism of lipids and endo-xenobiotics, and the GH-regulated endocrine, metabolic, immune, and male-specific responses. E2 induced a female-pattern of gene expression and inhibited GH-regulated STAT5b targeted genes. E2 did not prevent the inhibitory effects of GH on urea and amino acid metabolism-related genes. The combination of E2 and GH decreased transcriptional immune responses. E2 decreased the hepatic content of saturated fatty acids and induced a transcriptional program that seems to be mediated by the activation of PPARα. In contrast, GH inhibited fatty acid oxidation. Both E2 and GH replacements reduced hepatic CHO levels and increased the formation of cholesterol esters and triacylglycerols. Notably, the hepatic lipid profiles were endowed with singular fingerprints that may be used to segregate the effects of different hormonal replacements. In summary, we provide in vivo evidence that E2 has a significant impact on lipid content and transcriptome in male liver and that E2 exerts a marked influence on GH physiology, with implications in human therapy.
Nowadays robots play an important role in society, mainly due to the significant benefits they provide when utilized for assisting human beings in the execution of dangerous or repetitive tasks. ...Medicine is one of the fields in which robots are gaining greater use and development, especially those employed in minimally invasive surgery (MIS). However, due to the particular conditions of the human body where robots have to act, the design of these systems is complex, not only from a technical point of view, but also because the clinical needs and the normativity aspects are important considerations that have to be taken into account in order to achieve better performances and more secure systems for patients and surgeons. Thus, this paper explores the clinical needs and the technical requirements that will trace the roadmap for the next scientific and technological advances in the field of robotic surgery, the metrics that should be defined for safe technology development and the standards that are being elaborated for boosting the industry and facilitating systems integration.
Zinc-doped bismuth sulfide (Bi2-xZnxS3) nanocrystalline thin films were deposited on glass substrates by using an ultrasonic spray pyrolysis (USP) technique and their structural, morphological, ...electrical and optical properties experimentally addressed. X-ray diffraction (XRD) and micro-Raman spectroscopy have confirmed the generation of a single-phase polycrystalline orthorhombic material. The crystallite size and micro-deformation of the films was found to depend on the dopant concentration. The surface appears condensed and dense with a uniform spatial grain distribution, as revealed by scanning electron microscopy (SEM) images. Energy dispersive X-ray spectroscopy (EDS) studies revealed a certain Bi deficiency in both undoped and Zn-doped films. When the nominal Zn doping concentration increases from x = 0 to x = 0.09, the crystallite size decreases from 30 to 21 nm. The optical band gap of the films increased from 1.62 to 1.65 eV with Zn content increasing up to x = 0.06, then reducing to 1.58 eV for the maximum Zn content. Optical measurements showed a high absorption coefficient (α > 104 cm−1) in the visible and near-infrared ranges. The Urbach energy followed a similar behavior as a function of doping concentration. The electrical conductivity as well as the sheet carrier mobility of the Bi2-xZnxS3 films increase sharply by increasing the Zn content up to x = 0.06. For this doping concentration, mobility reaches 1.37 × 105 cm2/Vs while keeping carrier concentration above 1017 cm−3. Our experimental results provide strong evidence that Zn-doping is a suitable method to increase Bi2S3 light-harvesting efficiency in solar cell devices.
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•Zn doping improves the optoelectronic properties of USP-grown Bi2S3 films.•The highest conductivity (4×103 Ω cm−1) was measured in Bi1.94Zn0.06S3 films.•Zn doping increases the Bi2-xZnxS3 films optical band gap for x up to 0.06.•Doping with Zn increases charge carrier mobility, which might enhance our Bi2-xZnxS3 films light-harvesting capabilities.
The Geriatric Depression Scale is an instrument used to identify depression in people of an older age. The original English version of this scale has been translated into Spanish (GDS-
); two shorter ...versions of 5- (GDS-5) and 15-items (GDS-15) have been developed.
To assess the validity and compare the 5- and 15-item Spanish versions of the GDS among the Spanish population.
573 Galicia residents aged >50 years participated in this study. The following instruments were applied: the 19-item Control, Autonomy, Self-Realization and Pleasure scale, the Subjective Memory Complaints Questionnaire, the Mini-Mental State Examination test, the GDS-5, and the GDS-15.
We found differences in total score between GDS-5 and GDS-15 regarding the variable sex. Internal reliability for GDS-5 and GDS-15 was 0.495 and 0.715, respectively. Sensitivity and specificity for GDS-5 - with a cut-off value of 1 - was 0.517 and 0.650, respectively; for GDS-15 - with a cut-off value of 3 points - sensitivity was 0.755 and specificity 0.668. GDS-5 has a ROC curve of 0.617 and GDS-15 of 0.764.
GDS-15, and to a greater extent GDS-5, should be revised or even reformulated to improve their diagnostic usefulness by choosing higher discriminative ability items or even include new items with greater sensitivity that consider currently prevailing psychosocial factors.
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•Besnoitia besnoiti can invade and proliferate in primary bovine macrophages.•Besnoitia besnoiti induced morphological and transcriptomic changes in macrophages.•Host cell enriched ...pathways and parasite effectors were identified by dual RNA-Seq analysis.•Modulation of apoptosis and Herpes simplex virus 1 infection pathways could facilitate parasite dissemination.•Numerous rhoptry protein encoding genes were upregulated at 8 h p.i.
Besnoitia besnoiti-infected bulls may develop severe systemic clinical signs and orchitis that may ultimately cause sterility during the acute infection. Macrophages might play a relevant role in pathogenesis of the disease and the immune response raised against B. besnoiti infection. This study aimed to dissect the early interaction between B. besnoiti tachyzoites and primary bovine monocyte-derived macrophages in vitro. First, the B. besnoiti tachyzoite lytic cycle was characterized. Next, dual transcriptomic profiling of B. besnoiti tachyzoites and macrophages was conducted at early infection (4 and 8 h p.i.) by high-throughput RNA sequencing. Macrophages inoculated with heat-killed tachyzoites (MO-hkBb) and non-infected macrophages (MO) were used as controls. Besnoitia besnoiti was able to invade and proliferate in macrophages. Upon infection, macrophage activation was demonstrated by morphological and transcriptomic changes. Infected macrophages were smaller, round and lacked filopodial structures, which might be associated with a migratory phenotype demonstrated in other apicomplexan parasites. The number of differentially expressed genes (DEGs) increased substantially during infection. In B. besnoiti-infected macrophages (MO-Bb), apoptosis and mitogen-activated protein kinase (MAPK) pathways were regulated at 4 h p.i., and apoptosis was confirmed by TUNEL assay. The Herpes simplex virus 1 infection pathway was the only significantly enriched pathway in MO-Bb at 8 h p.i. Relevant DEGs of the Herpes simplex virus 1 infection (IFNα) and the apoptosis pathways (CHOP-2) were also significantly regulated in the testicular parenchyma of naturally infected bulls. Furthermore, the parasite transcriptomic analysis revealed DEGs mainly related to host cell invasion and metabolism. These results provide a deep overview of the earliest macrophage modulation by B. besnoiti that may favour parasite survival and proliferation in a specialized phagocytic immune cell. Putative parasite effectors were also identified.
The experiences and changes that come along with old age may lead to a feeling of loneliness, usually followed by negative physical and mental manifestations. In this systematic review, we evaluated ...the existing tools to assess loneliness in older adults.
We performed a literature search in the Web of Science, Medline, and PsycINFO, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After, we examined the psychometric properties of the instruments with a focus on reliability, validity, and main conclusions.
We included 27 articles published between 1996 and 2021.
To date, there are few instruments to assess loneliness in older adults. In general, they present adequate psychometric properties, although it is true that some scales show somewhat low levels of reliability and validity.
Highlights • Pervasive psychosocial health conditions exist among Latino MSM. • The presence of syndemic conditions was associated with sexual HIV risk behaviors. • To effectively curb HIV, multiple ...conditions must be addressed concurrently.
Introducción. Se analiza el impacto de la información sobre el COVID-19 en la población española para identificar los efectos y las emociones relacionadas con los canales y fuentes de consumo ...informativo durante la primera fase de la pandemia, que coincidió con los primeros días del estado de alarma. Metodología. Se realizó una encuesta administrada a través de Internet (n=1823.) que se distribuyó durante la segunda y la tercera semana de confinamiento (del 23 de marzo al 8 de abril de 2020) a toda la población mayor de edad residente en España y con acceso a internet. Resultados. Entre los resultados obtenidos destacan que, las noticias sobre la pandemia generaban en ese periodo diferentes emociones negativas -Tristeza, Ansiedad, Miedo, Confianza e Ira-, que variaban en función del canal de consumo informativo. Entre los temas que más interés tuvieron para los encuestados destacan los datos sobre la evolución de la pandemia, las medidas de protección y las formas de contagio; mientras que las fuentes más creíbles fueron las organizaciones y las autoridades oficiales, el personal sanitario y los medios de comunicación. Se aprueba la gestión de comunicación de crisis realizada por el Gobierno, que obtiene una nota media de 7,5 durante esta primera fase de la crisis. Se demuestra una circulación amplia de noticias falsas y de desinformación. Conclusión. Se demuestra la importancia de las emociones -en especial, las negativas- en las percepciones de la población en contextos de crisis como la del Covid-19 en España. En concreto, el Apoyo Emocional es el segundo mensaje oficial mejor valorado y, la Empatía, la característica más destacada de la información recibida. Se aprecia positivamente la capacidad del Gobierno por “entender” y “ponerse en lugar de la ciudadanía” por delante de cualquier otro aspecto.
•Identifying pro-atherogenic factors in rheumatic diseases can help prevent cardiovascular events.•Axial spondyloarthritis features associated with atherosclerosis remain unclear.•Inflammation and ...disease severity are associated with atherosclerosis in axial spondyloarthritis.
To identify disease-related factors associated with subclinical atherosclerosis and cardiovascular (CV) events in a large series of patients with axial spondyloarthritis (axSpA) and to identify possible differences in the effect of the potential pro-atherogenic factors between ankylosing spondylitis (AS) non-radiographic axSpA (nr-axSpA).
This is a cross-sectional observational study of the AtheSpAin cohort, a Spanish multicenter cohort to study atherosclerosis in axSpA. Subclinical atherosclerosis determined by carotid ultrasound included assessment of carotid intima-media thickness (cIMT) and plaque detection.
639 AS and 167 nr-axSpA patients were recruited. CV risk factors (CRF) and several disease-related factors showed a statistically significant association with subclinical atherosclerosis in the crude analysis. After adjustment for age, sex, and smoking (model 1), associations remained statistically significant for spinal mobility, inflammatory bowel disease, use of prednisone, and Disease-modifying antirheumatic drugs (DMARD) when assessing carotid plaques and for acute phase reactants (APR) at diagnosis, use of prednisone, DMARD, and TNF-inhibitors when measuring cIMT. In model 2, which also included classic CRF as confounding factors to identify axSpA features with a potential independent pro-atherogenic effect, the functional status was the only variable significantly associated with plaques and the use of prednisone and APR at diagnosis with cIMT. No association differences were found between both subtypes of patients. Besides, APR at diagnosis were also associated with subsequent development of CV events that had occurred in 33 patients.
Apart from CRF, atherosclerotic disease in AxSpA is associated with disease-related factors such as inflammatory response and disease severity, with no differences between AS and nr-axSpA.
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