Label-free detection of nosocomial bacteria using a nanophotonic interferometric biosensor

Nosocomial infections are a major concern at the worldwide level. Early and accurate identification of nosocomial pathogens is crucial to provide timely and adequate treatment. A prompt response also prevents the progression of the infection to life-threatening conditions, such as septicemia or generalized bloodstream infection. We have implemented two highly sensitive methodologies using an ultrasensitive photonic biosensor based on a bimodal waveguide interferometer (BiMW) for the fast detection of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA), two of the most prevalent bacteria associated with nosocomial infections. For that, we have developed a biofunctionalization strategy based on the use of a PEGylated silane (silane-PEG-COOH) which provides a highly resistant and bacteria-repelling surface, which is crucial to specifically detect each bacterium. Two different biosensor assays have been set under standard buffer conditions: One based on a specific direct immunoassay employing polyclonal antibodies for the detection of P. aeruginosa and another one employing aptamers for the direct detection of MRSA. The biosensor immunoassay for P. aeruginosa is fast (it only takes 12 min) and specific and has experimentally detected concentrations down to 800 cfu mL (cfu: Colony forming unit). The second one relies on the use of an aptamer that specifically detects penicillin-binding protein 2a (PBP2a), a protein only expressed in the MRSA mutant, providing a photonic biosensor with the ability to identify the resistant pathogen MRSA and differentiate it from methicillin-susceptible S. aureus (MSSA). Direct, label-free, and selective detection of whole MRSA bacteria has been achieved, making possible the direct detection of also 800 cfu mL. According to the signal-to-noise (S/N) ratio of the device, a theoretical limit of detection (LOD) of around 49 and 29 cfu mL was estimated for P. aeruginosa and MRSA, respectively. Both results obtained under standard conditions reveal the great potential this interferometric biosensor device has as a versatile and specific tool for bacterial detection and quantification, providing a rapid method for the identification of nosocomial pathogens within the clinical requirements of sensitivity for the diagnosis of infections

Principal Component Analysis Applied to Digital Pulse Shape Analysis for Isotope Discrimination

Digital pulse shape analysis (DPSA) techniques are becoming increasingly important for the study of nuclear reactions since the development of fast digitizers. These techniques allow us to obtain the (A, Z) values of the reaction products impinging on the new generation solid-state detectors. In this paper, we present a computationally efficient method to discriminate isotopes with similar energy levels, with the aim of enabling the edge-computing paradigm in future field-programmable gate-array-based acquisition systems. The discrimination of isotope pairs with analogous energy levels has been a topic of interest in the literature, leading to various solutions based on statistical features or convolutional neural networks. Leveraging a valuable dataset obtained from experiments conducted by researchers in the FAZIA Collaboration at the CIME cyclotron in GANIL laboratories, we aim to establish a comparative analysis regarding selectivity and computational efficiency, as this dataset has been employed in several prior publications. Specifically, this work presents an approach to discriminate between pairs of isotopes with similar energies, namely, 12,13C, 36,40Ar, and 80,84Kr, using principal component analysis (PCA) for data preprocessing. Consequently, a linear and cubic machine learning (ML) support vector machine (SVM) classification model was trained and tested, achieving a high identification capability, especially in the cubic one. These results offer improved computational efficiency compared to the previously reported methodologies.Grant TED2021-131075B-I00 funded byMCIN/AEI/10.13039/501100011033. Grant PID2021-127711NB-I00 funded by MCIN/AEI/10.13039/501100011033

Interplay between genetics and lifestyle on pain susceptibility in women with fibromyalgia: the al-Ándalus project

This work was supported by the Spanish Ministry of Economy and Competitiveness (I + D+i DEP2010-15639, I + D+i DEP2013-40908-R to M.D.-F.; BES-2014-067612 to F.E.-L.), the Spanish Ministry of Education (FPU13/03410 to D.S.-T.; FPU15/0002 to B.G.-C.), the Consejeria de Turismo, Comercio y Deporte, Junta de Andalucia (CTCD-201000019242-TRA to M.D.-F.), the Consejeria de Salud, Junta de Andalucia (PI-0520-2016 to M.D.-F.) and the University of Granada, Plan Propio de Investigacion 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES). The funders of the present study did not have any role in the study design, data collection and analyses, decision to publish or preparation of the manuscript.Objectives. It is widely acknowledged that the experience of pain is promoted by both genetic susceptibility and environmental factors such as engaging in physical activity (PA), and that pain-related cognitions are also important. Thus, the purpose of the present study was to test the association of 64 polymorphisms (34 candidate genes) and the gene–gene, gene–PA and gene–sedentary behaviour interactions with pain and pain-related cognitions in women with FM. Methods. Saliva samples from 274 women with FM [mean (S.D.) age 51.7 (7.7) years] were collected for extracting DNA. We measured PA and sedentary behaviour by accelerometers for a week, pain with algometry and questionnaires, and pain-related cognitions with questionnaires. To assess the robustness of the results, a meta-analysis was also performed. Results. The rs6311 and rs6313 polymorphisms (5-hydroxytryptamine receptor 2A, HTR2A) were individually related to algometer scores. The interaction of rs4818 (catechol-O-methyltransferase, COMT) and rs1799971 (opioid receptor l gene, OPRM1) was related to pain catastrophizing. Five gene–behaviour interactions were significant: the interactions of sedentary behaviour with rs1383914 (adrenoceptor alpha 1A, ADRA1A), rs6860 (charged multivesicular body protein 1A, CHMP1A), rs4680 (COMT), rs165599 (COMT) and rs12994338 (SCN9A) on bodily pain subscale of the Short Form 36. Furthermore, the meta-analysis showed an association between rs4680 (COMT) and severity of FM symptoms (codominant model, P-value 0.032). Conclusion. The HTR2A gene (individually), COMT and OPRM1 gene–gene interaction, and the interactions of sedentary behaviour with ADRA1A, CHMP1A, COMT and SCN9A genes were associated with pain-related outcomes. Collectively, findings from the present study indicate a modest contribution of genetics and gene– sedentary behaviour interaction to pain and pain catastrophizing in women with FM. Future research should examine whether reducing sedentary behaviour is particularly beneficial for reducing pain in women with genetic susceptibility to pain.Spanish Government I + D+i DEP2010-15639 I + D+i DEP2013-40908-R BES-2014-067612 FPU13/03410 FPU15/0002Junta de Andalucia CTCD-201000019242-TRA PI-0520-2016University of Granada, Plan Propio de InvestigacionUnit of Excellence on Exercise and Health (UCEES

Adhesion mechanisms of Actinobacillus pleuropneumoniae to the porcine respiratory system and biofilm formation

Actinobacillus pleuropneumoniae is a Gram-negative bacterium and the causative agent of porcine pleuropneumonia, a highly contagious disease of pigs characterised by fibrinohaemorrhagic necrotising pneumonia. Although it has been well controlled in some developed countries, outbreaks can occur in pigs of all ages in contact with asymptomatic carriers, leading to significant economic losses to the swine industry due to the high morbidity and mortality rates. Adhesion is a critical step in the colonisation of the swine respiratory tract and the pathogenesis of the porcine pleuropneumonia; however, a literature review of this process is not available to date. Therefore, this review aims to provide information regarding the molecules that have been described in the adhesion of A. pleuropneumoniae to cells and tissues of the porcine respiratory tract. Since adhesion is the first step in biofilm formation, we included a section to describe the genes involved in this process; some of these genes could participate directly or indirectly in the adhesion of A. pleuropneumoniae to the porcine respiratory system. Although the role of biofilms in porcine pleuropneumonia is still not clear, these molecules could be considered in the future as candidates for vaccine development

Historical and current evolution of the coastline on the beach of Somo (Cantabria), by using aerial photogrammetry and terrestrial laser scanning

Los trabajos topográficos llevados a cabo en la playa de Somo en el periodo 1988-1993 muestran ligeros cambios en la línea de costa. Para constatar estos cambios se ha estudiado el periodo 2001-2010 mediante fotogrametría, y desde el año 2011 se realizan dos mediciones anuales con láser escáner terrestre (TLS). Para este estudio, se ha seleccionado una porción de 400 metros en la playa de Somo, por coincidir con las mediciones del periodo 1988-1993. La aplicación de instrumentación geomática (GPS, estación total, TLS) y fotogrametría aérea ha permitido establecer dos grupos de periodos con comportamientos netamente diferentes. Un grupo donde no hay casi retroceso de la línea de costa arenosa: 1988-1993, 2001-2013, y otro grupo de retroceso acentuado: 1994-2000 y 2014. Este último año coincidieron temporales de grandes olas (mayores a 5 m) y mareas vivas que provocaron retrocesos de mayor rango en la línea de costa

Exosomes as Hedgehog carriers in cytoneme-mediated transport and secretion

The Hedgehog signalling pathway is crucial for development, adult stem cell maintenance, cell migration and axon guidance in a wide range of organisms. During development, the Hh morphogen directs tissue patterning according to a concentration gradient. Lipid modifications on Hh are needed to achieve graded distribution, leading to debate about how Hh is transported to target cells despite being membrane-tethered. Cytonemes in the region of Hh signalling have been shown to be essential for gradient formation, but the carrier of the morphogen is yet to be defined. Here we show that Hh and its co-receptor Ihog are in exovesicles transported via cytonemes. These exovesicles present protein markers and other features of exosomes. Moreover, the cell machinery for exosome formation is necessary for normal Hh secretion and graded signalling. We propose Hh transport via exosomes along cytonemes as a significant mechanism for the restricted distribution of a lipid-modified morphogen.PostprintPeer reviewe

Synthesis, antibacterial and antifungal activities of naphthoquinone derivatives: a structure–activity relationship study

The synthesis of 1,4-naphthoquinone derivatives is of great interest since these compounds exhibit strong activity as antimalarial, antibacterial, antifungal and anticancer agents. A series of 50 naphthoquinone derivatives was synthesized and evaluated for antibacterial and antifungal activity against Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, Candida krusei, Candida parapsilosis and Cryptococcus neoformans using the broth microdilution method. The Candida species were the most susceptible microorganisms. Halogen derivatives of 1,4-naphthoquinone presented strong activity, e.g., 2-bromo-5-hydroxy-1,4-naphthoquinone, which exhibited inhibition at an MIC of 16 lg/ mL in S. aureus, and 2-chloro-5,8-dihydroxy-1,4-naphthoquinone, with an MIC of 2 lg/mL in C. krusei. These compounds showed higher activity against fungi, but the antibacterial activities were very low. The study of structure–activity relationships is very important in the search for new antimicrobial drugs due to the limited therapeutic arsenal

His452Tyr polymorphism in the human 5-HT2A receptor affects clozapine-induced signaling networks revealed by quantitative phosphoproteomics

Antipsychotic drugs remain the current standard for schizophrenia treatment. Although they directly recognize the orthosteric binding site of numerous monoaminergic G protein-coupled receptors (GPCRs), these drugs, and particularly second-generation antipsychotics such as clozapine, all have in common a very high affinity for the serotonin 5-HT receptor (5-HTR). Using classical pharmacology and targeted signaling pathway assays, previous findings suggest that clozapine and other atypical antipsychotics behave principally as 5-HTR neutral antagonists and/or inverse agonists. However, more recent findings showed that antipsychotics may also behave as pathway-specific agonists. Reversible phosphorylation is a common element in multiple signaling networks. Combining a quantitative phosphoproteomic method with signaling network analysis, we tested the effect of clozapine treatment on the overall level of protein phosphorylation and signal transduction cascades in vitro in mammalian cell lines induced to express either the human 5-HTR or the H452Y variant of the gene encoding the 5-HTR receptor. This naturally occurring variation within the 5-HTR gene was selected because it has been repeatedly associated with schizophrenia patients who do not respond to clozapine treatment. Our data show that short time exposure (5 or 10 min) to clozapine (10 M) led to phosphorylation of numerous signaling components of pathways involved in processes such as endocytosis, ErbB signaling, insulin signaling or estrogen signaling. Cells induced to express the H452Y variant showed a different basal phosphoproteome, with increases in the phosphorylation of mTOR signaling components as a translationally relevant example. However, the effect of clozapine on the functional landscape of the phosphoproteome was significantly reduced in cells expressing the 5-HTR-H452Y construct. Together, these findings suggest that clozapine behaves as an agonist inducing phosphorylation of numerous pathways downstream of the 5-HTR, and that the single nucleotide polymorphism encoding 5-HTR-H452Y affects these clozapine-induced phosphorylation-dependent signaling networks

TOX3 rs3803662 Polymorphism Is Associated With Breast Cancer Protection In Northeastern Mexican Woman

Introduction: Low penetrance genes are involved in breast cancer (BC) and confer risk for the development of this neoplasia. Different single nucleotide polymorphisms (SNPs) associated with BC have been identified, such as rs3803662 (TOX3), which is related to estrogen receptors in European and African-American women. The contribution of this variant in the Mexican population is unknown. The objective of this study was to evaluate, through a case-control design, the association of the SNP rs3803662 (TOX3), with the risk of BC in women from northeastern Mexico. Methods: We included 434 cases and 228 controls. Genotyping was carried out using RFLPs. The SPSS 7.0 statistical program was used to determine the gene frequencies, the estimation of the relative risk (Odds ratio [OR]), and the Hardy-Weinberg equilibrium (EHW). Results: The homocygote (T/T) genotype of the SNP TOX3 rs3803662 was identified as a protective allele for BC (OR: 0.47, 95% CI: 0.29 - 0.78). Conclusions; The T allele of the SNP rs3803662 can be considered as a protective factor for BC from northeastern Mexico women

Impact of the COVID-19 pandemic in Spain in the successive pandemic waves on hemodialysis patients and healthcare personnel

(1) Background: The impact of SARS-CoV-2 has been variable over the time course of the pandemic and in different populations. The aim was to analyze the impact of COVID-19 infection in a known population of hemodialysis (HD) patients and professionals in Spain at different times of the pandemic. (2) Methods: We conducted an observational, descriptive study with a follow-up from 3 March 2020 to 23 April 2022 (776 days), using in average of 414 professionals and 1381 patients from 18 HD units in Spain. The data from the positive PCR or the rapid antigen detection test (RADT) subject were analyzed and segmented into six periods (waves). (3) Results: Of 703 positive COVID-19 tests, 524 were HD patients (74.5%), and 179 were HD professionals (25.5%). Overall, 38% of staff and 43% of patients were affected. Differences were observed in regard to incidence (21% vs. 13%), mortality (3.5% vs. 0%), and symptomatology between the patients and professionals and throughout the pandemic. (4) Conclusions: COVID-19 severity varied during different pandemic waves, with a greater impact seen in the first wave. HD professionals and patients had similar infection rates, but patients had higher mortality rates. Community transmission was the primary route of infection.This research received was founded by Fundación Renal Íñigo Álvarez de Toledo (FRIAT). The research groups of S.M.-F. and E.G.-P. are funded by the Ministerio de Economia, Industria y competitividad: FIS/Fondos FEDER (PI20/00487; PI21/01430). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Financiadores Fundación Renal Íñigo Álvarez de Toledo Ministerio de Economia Federación Española de Enfermedades Raras Spain PI21/0143