Sex differences in patient-reported outcome measure of psychotic symptoms in schizophrenia.

PURPOSE: to study sex differences in self-reported symptoms measured with the Scale of Patient-Reported Impact of Symptoms in Schizophrenia (PRISS), to investigated sex differences in the degree of agreements between self-reported symptoms and clinical symptoms assessed by professionals, and to identify which clinical and sociodemographic variables predicted a greater presence of self-reported symptoms split by sex. METHODS: 161 patients (37 females; 124 males), aged between 18 and 65 years, with a diagnosis of schizophrenia assisted in non-acute mental health services at four mental health catchment areas in Andalucia and Catalonia were included. The PRISS scale was administered to asses self-reported symptoms. RESULTS: males reported higher presence of excitement, grandiosity, motor retardation and poor attention) than women. There was less agreement in the presence of psychotic symptoms in men than in women when comparing self-reported symptoms and clinical symptoms assessed by professionals. Finally, in men the predictors variables for the greater presence of self-perceived symptoms were greater psychotic symptomatology and more disability, while in women were greater presence of alogia and higher doses of chlorpromazine. CONCLUSIONS: Assessing and being aware of the self-perceived symptoms of patients with schizophrenia should be considered in the clinic, especially in men, as there appears to be a lack of agreement on certain items. This would allow treatments to be more focused on patients' need by sex, and would make them feel part of the therapeutic process, improving their therapeutic adherence, evolution and quality of life.

Influence of microbiota-driven natural antibodies on dengue transmission.

Dengue has had a significant global health impact, with a dramatic increase in incidence over the past 50 years, affecting more than 100 countries. The absence of a specific treatment or widely applicable vaccine emphasizes the urgent need for innovative strategies. This perspective reevaluates current evidence supporting the concept of dual protection against the dengue virus (DENV) through natural antibodies (NAbs), particularly anti-α-Gal antibodies induced by the host's gut microbiome (GM). These anti-α-Gal antibodies serve a dual purpose. Firstly, they can directly identify DENV, as mosquito-derived viral particles have been observed to carry α-Gal, thereby providing a safeguard against human infections. Secondly, they possess the potential to impede virus development in the vector by interacting with the vector's microbiome and triggering infection-refractory states. The intricate interplay between human GM and NAbs on one side and DENV and vector microbiome on the other suggests a novel approach, using NAbs to directly target DENV and simultaneously disrupt vector microbiome to decrease pathogen transmission and vector competence, thereby blocking DENV transmission cycles.

Adaptation and Validation of the 3 × 2 Achievement Goals Questionnaire in a Population of Athletes.

(1) Background: Sport goals, although widely recognised as crucial for motivation and performance in sport, are multifaceted and can be difficult to measure directly. The present research aims to validate the 3 × 2 achievement goals questionnaire of Mascret in Spanish in a population of athletes. (2) Method: By using a latent factor approach, it is possible to identify the underlying dimensions of these goals and to better understand how they are structured. For this purpose, this questionnaire has been translated and compared with the life satisfaction scale. An exploration of the multifaceted nature of sport goals has been carried out using structural equation modelling. A total of 580 athletes (463 males and 216 females, M = 21.5, SD = 2.36) from different sport disciplines and from 12 autonomous communities in Spain participated in the research. (3) Results: The results show that the questionnaire presents a high scale reliability and that all items contribute significantly to the internal consistency of the scale. (4) Conclusions: The adaptation of this scale to the Spanish population of athletes can be a valid and useful tool to measure and understand motivation and goals in the sport context.

Evolution and advancements in genomics and epigenomics in OA research: How far we have come.

OBJECTIVE: Osteoarthritis (OA) is the most prevalent musculoskeletal disease affecting articulating joint tissues, resulting in local and systemic changes that contribute to increased pain and reduced function. Diverse technological advancements have culminated in the advent of high throughput "omic" technologies, enabling identification of comprehensive changes in molecular mediators associated with the disease. Amongst these technologies, genomics and epigenomics - including methylomics and miRNomics, have emerged as important tools to aid our biological understanding of disease. DESIGN: In this narrative review, we selected articles discussing advancements and applications of these technologies to OA biology and pathology. We discuss how genomics, deoxyribonucleic acid (DNA) methylomics, and miRNomics have uncovered disease-related molecular markers in the local and systemic tissues or fluids of OA patients. RESULTS: Genomics investigations into the genetic links of OA, including using genome-wide association studies, have evolved to identify 100+ genetic susceptibility markers of OA. Epigenomic investigations of gene methylation status have identified the importance of methylation to OA-related catabolic gene expression. Furthermore, miRNomic studies have identified key microRNA signatures in various tissues and fluids related to OA disease. CONCLUSIONS: Sharing of standardized, well-annotated omic datasets in curated repositories will be key to enhancing statistical power to detect smaller and targetable changes in the biological signatures underlying OA pathogenesis. Additionally, continued technological developments and analysis methods, including using computational molecular and regulatory networks, are likely to facilitate improved detection of disease-relevant targets, in-turn, supporting precision medicine approaches and new treatment strategies for OA.

Identification of circulating autoantibodies to non-modified proteins associated with ACPA status in early rheumatoid arthritis.

OBJECTIVES: To discover autoantibodies to non-modified proteins associated with the presence/absence of anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA). METHODS: The autoantibody repertoire of 80 ACPA negative and 80 ACPA positive RA subjects from the Swedish population-based Epidemiological Investigation of RA (EIRA) cohort was screened using a suspension bead array built on protein fragments earlier described as autoimmunity targets. Four autoantibodies positive in the initial screening were validated in another set of EIRA samples containing 317 ACPA-positive, 302 ACPA-negative and 372 age- and sex-matched controls. The relationship between the four autoantibodies and lung abnormalities on high-resolution computed tomography (HRTC) was examined in 93 early RA patients from LURA cohort. Association between the autoantibodies, smoking and MHC class II alleles was assessed by logistic regression analysis. RESULTS: : Anti-ANOS1 and anti-MURC IgG levels were associated with ACPA-positive status (OR = 3.02; 95% CI 1.87-4.89; and OR = 1.86; 95% CI 1.16-2.97, respectively) and increased in ACPA-positive patients compared with controls. Anti-ANOS1 IgG was associated with smoking habit (OR = 2.11; 95% CI 1.22-3.69) and anti-MURC IgG with the presence of the MHC class II "shared-epitope" genes (OR = 1.95; 95% CI 1.11-3.46). Anti-TSPYL4 IgG was associated with ACPA-negative (OR = 0.41; 95% CI 0.19-0.89). Anti-TSPYL4 IgG and anti-MAP2K6 IgG levels were increased in the ACPA-negative patients compared with controls. Presence of anti-MAP2K6 IgG and anti-TSPYL4 IgG correlated negatively with HRCT-defined lung abnormalities. CONCLUSIONS: These four autoantibodies may be useful in diagnostics and in predicting clinical phenotypes of RA.

Prognostic model to predict the incidence of radiographic knee osteoarthritis.

OBJECTIVE: Early diagnosis of knee osteoarthritis (KOA) in asymptomatic stages is essential for the timely management of patients using preventative strategies. We develop and validate a prognostic model useful for predicting the incidence of radiographic KOA (rKOA) in non-radiographic osteoarthritic subjects and stratify individuals at high risk of developing the disease. METHODS: Subjects without radiographic signs of KOA according to the Kellgren and Lawrence (KL) classification scale (KL=0 in both knees) were enrolled in the OA initiative (OAI) cohort and the Prospective Cohort of A Coruña (PROCOAC). Prognostic models were developed to predict rKOA incidence during a 96-month follow-up period among OAI participants based on clinical variables and serum levels of the candidate protein biomarkers APOA1, APOA4, ZA2G and A2AP. The predictive capability of the biomarkers was assessed based on area under the curve (AUC), and internal validation was performed to correct for overfitting. A nomogram was plotted based on the regression parameters. Model performance was externally validated in the PROCOAC. RESULTS: 282 participants from the OAI were included in the development dataset. The model built with demographic, anthropometric and clinical data (age, sex, body mass index and WOMAC pain score) showed an AUC=0.702 for predicting rKOA incidence during the follow-up. The inclusion of ZA2G, A2AP and APOA1 data significantly improved the model's sensitivity and predictive performance (AUC=0.831). The simplest model, including only clinical covariates and ZA2G and A2AP serum levels, achieved an AUC=0.826. Both models were internally cross-validated. Predictive performance was externally validated in an independent dataset of 100 individuals from the PROCOAC (AUC=0.713). CONCLUSION: A novel prognostic model based on common clinical variables and protein biomarkers was developed and externally validated to predict rKOA incidence over a 96-month period in individuals without any radiographic signs of disease. The resulting nomogram is a useful tool for stratifying high-risk populations and could potentially lead to personalised medicine strategies for treating OA.

Three decades of advancements in osteoarthritis research: insights from transcriptomic, proteomic, and metabolomic studies.

OBJECTIVE: Osteoarthritis (OA) is a complex disease involving contributions from both local joint tissues and systemic sources. Patient characteristics, encompassing sociodemographic and clinical variables, are intricately linked with OA rendering its understanding challenging. Technological advancements have allowed for a comprehensive analysis of transcripts, proteomes and metabolomes in OA tissues/fluids through omic analyses. The objective of this review is to highlight the advancements achieved by omic studies in enhancing our understanding of OA pathogenesis over the last three decades. DESIGN: We conducted an extensive literature search focusing on transcriptomics, proteomics and metabolomics within the context of OA. Specifically, we explore how these technologies have identified individual transcripts, proteins, and metabolites, as well as distinctive endotype signatures from various body tissues or fluids of OA patients, including insights at the single-cell level, to advance our understanding of this highly complex disease. RESULTS: Omic studies reveal the description of numerous individual molecules and molecular patterns within OA-associated tissues and fluids. This includes the identification of specific cell (sub)types and associated pathways that contribute to disease mechanisms. However, there remains a necessity to further advance these technologies to delineate the spatial organization of cellular subtypes and molecular patterns within OA-afflicted tissues. CONCLUSIONS: Leveraging a multi-omics approach that integrates datasets from diverse molecular detection technologies, combined with patients' clinical and sociodemographic features, and molecular and regulatory networks, holds promise for identifying unique patient endophenotypes. This holistic approach can illuminate the heterogeneity among OA patients and, in turn, facilitate the development of tailored therapeutic interventions.

Proteomic profiling of human menisci from mild joint degeneration and end-stage osteoarthritis versus healthy controls.

Objective: To gain new insight into the molecular changes of the meniscus by comparing the proteome profiles of healthy controls with mild degeneration and end-stage osteoarthritis (OA). Method: We obtained tissue plugs from lateral and medial menisci of 37 individuals (central part of the posterior horn) classified as healthy (n â€‹= â€‹12), mild signs of joint damage (n â€‹= â€‹13) and end-stage OA (n â€‹= â€‹12). The protein profile was analysed by nano-liquid chromatography-mass spectrometry using data-independent acquisition and quantified by Spectronaut. Linear-mixed effects modelling was applied to extract the between-group comparisons. Results: A similar protein profile was observed for the mild group as compared to healthy controls while the most different group was end-stage OA mainly for the medial compartment. When a pattern of gradual change in protein levels from healthy to end-stage OA was required, a 42-proteins panel was identified, suggesting a potential role in OA development. The levels of QSOX1 were lower and G6PD higher in the mild group following the proposed protein abundance pattern. Qualitative protein changes suggest lower levels of CYTL1 as a potential biomarker of early joint degradation. Conclusion: For future targeted proteomic approaches, we propose a candidate panel of 42 proteins based on gradually altered meniscal posterior horn protein abundance patterns associated with joint degradation.

An Atlas of the Knee Joint Proteins and Their Role in Osteoarthritis Defined by Literature Mining.

Osteoarthritis (OA) is the most prevalent rheumatic pathology. However, OA is not simply a process of wear and tear affecting articular cartilage but rather a disease of the entire joint. One of the most common locations of OA is the knee. Knee tissues have been studied using molecular strategies, generating a large amount of complex data. As one of the goals of the Rheumatic and Autoimmune Diseases initiative of the Human Proteome Project, we applied a text-mining strategy to publicly available literature to collect relevant information and generate a systematically organized overview of the proteins most closely related to the different knee components. To this end, the PubPular literature-mining software was employed to identify protein-topic relationships and extract the most frequently cited proteins associated with the different knee joint components and OA. The text-mining approach searched over eight million articles in PubMed up to November 2022. Proteins associated with the six most representative knee components (articular cartilage, subchondral bone, synovial membrane, synovial fluid, meniscus, and cruciate ligament) were retrieved and ranked by their relevance to the tissue and OA. Gene ontology analyses showed the biological functions of these proteins. This study provided a systematic and prioritized description of knee-component proteins most frequently cited as associated with OA. The study also explored the relationship of these proteins to OA and identified the processes most relevant to proper knee function and OA pathophysiology.

Ozone Efficacy for the Disinfection of Ambulances Used to Transport Patients during the COVID-19 Pandemic in Peru.

We assessed the disinfection efficacy of an ozone generator prototype in ambulances used to transport patients with coronavirus disease (COVID-19). This research consisted of three stages: in vitro tests using microbial indicators, such as Candida albicans, Escherichia coli, Staphylococcus aureus and Salmonella phage, which were experimentally inoculated onto polystyrene crystal surfaces within a 23 m3 enclosure. They were then exposed to ozone at a 25 ppm concentration using the ozone generator (Tecnofood SAC) portable prototype, and the decimal reduction time (D) was estimated for each indicator. The second stage involved the experimental inoculation of the same microbial indicators on a variety of surfaces inside conventional ambulances. The third stage consisted of exploratory field testing in ambulances used to transport patients with suspected COVID-19. During the second and third stages, samples were collected by swabbing different surfaces before and after 25 ppm ozonisation for 30 min. Results suggested that ozone was most effective on Candida albicans (D = 2.65 min), followed by Escherichia coli (D = 3.14 min), Salmonella phage (D = 5.01 min) and Staphylococcus aureus (D = 5.40 min). Up to 5% of the microbes survived following ozonisation of conventional ambulances. Of the 126 surface samples collected from ambulances transporting patients with COVID-19, 7 were positive (5.6%) for SARS-related coronavirus as determined on reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Ozone exposure from the ozone generator prototype inside ambulances at a concentration of 25 ppm for 30 min can eliminate gram positive and negative bacteria, yeasts, and viruses.

A meta-analysis and a functional study support the influence of mtDNA variant m.16519C on the risk of rapid progression of knee osteoarthritis.

OBJECTIVES: To identify mitochondrial DNA (mtDNA) genetic variants associated with the risk of rapid progression of knee osteoarthritis (OA) and to characterise their functional significance using a cellular model of transmitochondrial cybrids. METHODS: Three prospective cohorts contributed participants. The osteoarthritis initiative (OAI) included 1095 subjects, the Cohort Hip and Cohort Knee included 373 and 326 came from the PROspective Cohort of Osteoarthritis from A Coruña. mtDNA variants were screened in an initial subset of 450 subjects from the OAI by in-depth sequencing of mtDNA. A meta-analysis of the three cohorts was performed. A model of cybrids was constructed to study the functional consequences of harbouring the risk mtDNA variant by assessing: mtDNA copy number, mitochondrial biosynthesis, mitochondrial fission and fusion, mitochondrial reactive oxygen species (ROS), oxidative stress, autophagy and a whole transcriptome analysis by RNA-sequencing. RESULTS: mtDNA variant m.16519C is over-represented in rapid progressors (combined OR 1.546; 95% CI 1.163 to 2.054; p=0.0027). Cybrids with this variant show increased mtDNA copy number and decreased mitochondrial biosynthesis; they produce higher amounts of mitochondrial ROS, are less resistant to oxidative stress, show a lower expression of the mitochondrial fission-related gene fission mitochondrial 1 and an impairment of autophagic flux. In addition, its presence modulates the transcriptome of cybrids, especially in terms of inflammation, where interleukin 6 emerges as one of the most differentially expressed genes. CONCLUSIONS: The presence of the mtDNA variant m.16519C increases the risk of rapid progression of knee OA. Among the most modulated biological processes associated with this variant, inflammation and negative regulation of cellular process stand out. The design of therapies based on the maintenance of mitochondrial function is recommended.

Bioinspired Synthesis of Magnetic Nanoparticles Based on Iron Oxides Using Orange Waste and Their Application as Photo-Activated Antibacterial Agents.

Magnetic nanoparticles based on iron oxides (MNPs-Fe) have been proposed as photothermal agents (PTAs) within antibacterial photothermal therapy (PTT), aiming to counteract the vast health problem of multidrug-resistant bacterial infections. We present a quick and easy green synthesis (GS) to prepare MNPs-Fe harnessing waste. Orange peel extract (organic compounds) was used as a reducing, capping, and stabilizing agent in the GS, which employed microwave (MW) irradiation to reduce the synthesis time. The produced weight, physical-chemical features and magnetic features of the MNPs-Fe were studied. Moreover, their cytotoxicity was assessed in animal cell line ATCC RAW 264.7, as well as their antibacterial activity against Staphylococcus aureus and Escherichia coli. We found that the 50GS-MNPs-Fe sample (prepared by GS, with 50% v/v of NH4OH and 50% v/v of orange peel extract) had an excellent mass yield. Its particle size was ~50 nm with the presence of an organic coating (terpenes or aldehydes). We believe that this coating improved the cell viability in extended periods (8 days) of cell culture with concentrations lower than 250 µg·mL-1, with respect to the MNPs-Fe obtained by CO and single MW, but it did not influence the antibacterial effect. The bacteria inhibition was attributed to the plasmonic of 50GS-MNPs-Fe (photothermal effect) by irradiation with red light (630 nm, 65.5 mW·cm-2, 30 min). We highlight the superparamagnetism of the 50GS-MNPs-Fe over 60 K in a broader temperature range than the MNPs-Fe obtained by CO (160.09 K) and MW (211.1 K). Therefore, 50GS-MNPs-Fe could be excellent candidates as broad-spectrum PTAs in antibacterial PTT. Furthermore, they might be employed in magnetic hyperthermia, magnetic resonance imaging, oncological treatments, and so on.

Estrategias de afrontamiento durante el confinamiento por COVID-19 en pacientes con primer episodio psicótico: el impacto en su vida diaria / Coping strategies during covid-19 lockdown in patients with first-episode psychosis: the impact on their daily life

Introducción: El confinamiento por la enfermedad del coronavirus 2019 (COVID-19) interrumpió la vida de todo el mundo en marzo de 2020. El confinamiento obligatorio duró dos meses, lo que tuvo un impacto en la salud mental de las personas. Sin embargo, se desconoce en gran medida cómo afectó a quienes ya luchaban con problemas de salud mental. Métodos: Se recopiló información de 18 pacientes con primer episodio psicótico (PEP) mediante una encuesta en línea. La encuesta tenía preguntas sobre COVID-19, el impacto del confinamiento en la vida diaria y las estrategias de afrontamiento utilizadas durante el confinamiento entre marzo y abril de 2020 en España. Resultados: Algunas estrategias de afrontamiento se asociaron con diferentes actividades de la vida diaria: normalizar la situación, buscar ayuda de amigos o familiares y buscar ayuda de profesionales en situaciones estresantes, leer fuentes de información y autoayuda para enfrentar el estrés, enfocarse en las emociones que generan estrés, intentar centrarse en problemas concretos y buscar soluciones, y aceptar la situación con resignación. Conclusiones: Como conclusión, los resultados sugieren que no todas las estrategias de afrontamiento impactaron de la misma manera en la vida diaria de los/las pacientes con PEP durante el confinamiento por COVID-19.(AU)

Introduction: Lockdown for 2019 coronavirus disease (COVID-19) disrupted life worldwide from March 2020. Mandatory lockdown lasted two months, which had an impact on people’s mental health. However, how it affected those who already struggled with mental health problems is largely unknown. Methods: We collected information from 18 patients with first-episode psychosis (FEP) through an online survey. The survey contained questions regarding COVID-19, impact of confinement on daily life, and coping strategies during lockdown between March and April 2020 in Spain. Results: Some coping strategies were associated with different daily life activities: normalizing the situation, seeking help from friends or family, and seeking help from professionals in stressful situations, reading information sources and self-help to cope with stress, focusing on the emotions that generate stress, trying to focus on specific problems and seek solutions, and accepting the situation with resignation. Discussion: As a conclusion, results suggest that not all coping strategies impacted in the same way in daily life of patients with FEP during COVID-19 lockdown.(AU)

Feasibility of family-directed home-based bimanual intensive therapy combined with modified constraint induced movement therapy (h-BITmCI) in very low and low bimanual functional level: A brief report.

OBJECTIVE: To examine the feasibility of a home-based hybrid Bimanual-Intensive-Therapy combined with modified Constraint-Induced-Movement-Therapy (h-BITmCI) in children with spastic unilateral cerebral palsy (SUCP) with low and very low bimanual functional level. METHODS: A single-group of 10 children aged 5-8 years old, performed the hybrid home Bimanual-Intensive-Therapy (BIT, 80 hours) combined with modified Constraint-Induced-Movement-Therapy (mCIMT, 20 hours): h-BITmCI. Thus, Bimanual Functional Performance (BFP), Quality of Life (QoL) and expectations from families were measured through the Assisting Hand Assessment, (AHA), Pediatric Quality of Life Inventory, for Cerebral Palsy, (PedsQLTM v. 3.0, CP) and a specific questionnaire for families for baseline period (week 0), during the treatment phase (week 4 and week 8) and after the intervention (week 10). Repeated measures ANOVA analysis (with post hoc test correction) was used for the BFP and QoL, with a confidence interval (CI) of 95% and with p value <.008 considered statistically significant. RESULTS: Ten children completed the study with an average of 77-hours-BIT and 17-hours-mCIMT. None of the participants dropped out of the study during the follow-up process, and the parents' expectations were fulfilled, indicating high caregiver compliance. During the first 80 hours of BIT, a mean increase of 3.7 AHA units was obtained for the BFP (p = 1.00) and 1.64 points in the QoL (p = 1.00). Clinically relevant changes were observed in the last two weeks (20 hours mCIMT) with a mean increase of 10.6 AHA units in BFP and 6.29 points in QoL (p < .001). CONCLUSIONS: h-BITmCI protocol is feasible to be performed at home with the family's involvement, obtaining the greatest improvements after 100 hours of both therapies. Thus, mCIMT would be a relevant condition to increase the affected upper limb functionality, rather than the dosage used to obtain clinically relevant changes.

Exploring High-Throughput Immunoassays for Biomarker Validation in Rheumatic Diseases in the Context of the Human Proteome Project.

Rheumatic diseases are high prevalence pathologies with different etiology and evolution and low sensitivity in clinical diagnosis. Therefore, it is necessary to develop an early diagnosis method which allows personalized treatment, depending on the specific pathology. The biology/disease initiative, at Human Proteome Project, is an integrative approach to identify relevant proteins in the human proteome associated with pathologies. A previously reported literature data mining analysis, which identified proteins related to osteoarthritis (OA), rheumatoid arthritis (RA), and psoriatic arthritis (PSA) was used to establish a systematic prioritization of potential biomarkers candidates for further evaluation by functional proteomics studies. The aim was to study the protein profile of serum samples from patients with rheumatic diseases such as OA, RA, and PSA. To achieve this goal, customized antibody microarrays (containing 151 antibodies targeting 121 specific proteins) were used to identify biomarkers related to early and specific diagnosis in a screening of 960 serum samples (nondepleted) (OA, n = 480; RA, n = 192; PSA, n = 288). This functional proteomics screening has allowed the determination of a panel (30 serum proteins) as potential biomarkers for these rheumatic diseases, displaying receiver operating characteristics curves with area under the curve values of 80-90%.

Association of the serological status of rheumatoid arthritis patients with two circulating protein biomarkers: A useful tool for precision medicine strategies.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints and presence of systemic autoantibodies, with a great clinical and molecular heterogeneity. Rheumatoid Factor (RF) and anti-citrullinated protein antibodies (ACPA) are routinely used for the diagnosis of RA. However, additional serological markers are needed to improve the clinical management of this disease, allowing for better patient stratification and the desirable application of precision medicine strategies. In the present study, we investigated those systemic molecular changes that are associated with the RF and ACPA status of RA patients. To achieve this objective, we followed a proteomic biomarker pipeline from the discovery phase to validation. First, we performed an iTRAQ-based quantitative proteomic experiment on serum samples from the RA cohort of the Hospital of Santiago de Compostela (CHUS). In this discovery phase, serum samples from the CHUS cohort were pooled according to their RF/ACPA status. Shotgun analysis revealed that, in comparison with the double negative group (RF-/ACPA-), the abundance of 12 proteins was altered in the RF+/ACPA+ pool, 16 in the RF+/ACPA- pool and 10 in the RF-/ACPA+ pool. Vitamin D binding protein and haptoglobin were the unique proteins increased in all the comparisons. For the verification phase, 80 samples from the same cohort were analyzed individually. To this end, we developed a Multiple Reaction Monitoring (MRM) method that was employed in a comprehensive targeted analysis with the aim of verifying the results obtained in the discovery phase. Thirty-one peptides belonging to 12 proteins associated with RF and/or ACPA status were quantified by MRM. In a final validation phase, the serum levels of alpha-1-acid glycoprotein 1 (A1AG1), haptoglobin (HPT) and retinol-binding protein 4 (RET4) were measured by immunoassays in the RA cohort of the Hospital of A Coruña (HUAC). The increase of two of these putative biomarkers in the double seropositive group was validated in 260 patients from this cohort (p = 0.009 A1AG1; p = 0.003 HPT). The increased level of A1AG1 showed association with RF rather than ACPA (p = 0.023), whereas HPT showed association with ACPA rather than RF (p = 0.013). Altogether, this study has allowed a further classification of the RA seropositive patients into two novel clusters: RF+A1AG+ and ACPA+HPT+. The determination of A1AG1 and HPT in serum would provide novel information useful for RA patient stratification, which could facilitate the effective implementation of personalized medicine in routine clinical practice.

Excretion and viability of SARS-CoV-2 in feces and its association with the clinical outcome of COVID-19.

The main objective was to evaluate the viability of the SARS-CoV-2 viral particles excreted in stools. In addition, we aimed to identify clinical factors associated with the detection of SARS-CoV-2 RNA in feces, and to determine if its presence is associated with an unfavorable clinical outcome, defined as intensive care unit (ICU) admission and/or death. A prospective multicenter cohort study of COVID-19 adult patients, with confirmed SARS-CoV-2 infection by RT-PCR assay in nasopharyngeal (NP) swabs admitted to four hospitals in Spain, from March 2020 to February 2021. Sixty-two adult COVID-19 patients had stool samples collected at admission and/or during the follow up, with a total of 79 stool samples. SARS-CoV-2 RNA was detected in stool samples from 27 (43.5%) out of the 62 patients. Replicative virus, measured by the generation of cytopathic effect in cell culture and subsequent RT-PCR confirmation of a decrease in the Ct values, was not found in any of these stool samples. Fecal virus excretion was not associated with the presence of gastrointestinal symptoms, or with differences in the evolution of COVID-19 patients. Our results suggest that SARS-CoV-2 replicative capacity is null or very limited in stool samples, and thus, the fecal-oral transmission of SARS-CoV-2 as an alternative infection route is highly unlikely. In our study, the detection of SARS-CoV-2 RNA in feces at the beginning of the disease is not associated with any clinical factor nor with an unfavorable clinical outcome.

Broad-Spectrum Antimicrobial ZnMintPc Encapsulated in Magnetic-Nanocomposites with Graphene Oxide/MWCNTs Based on Bimodal Action of Photodynamic and Photothermal Effects.

Microbial diseases have been declared one of the main threats to humanity, which is why, in recent years, great interest has been generated in the development of nanocomposites with antimicrobial capacity. The present work studied two magnetic nanocomposites based on graphene oxide (GO) and multiwall carbon nanotubes (MWCNTs). The synthesis of these magnetic nanocomposites consisted of three phases: first, the synthesis of iron magnetic nanoparticles (MNPs), second, the adsorption of the photosensitizer menthol-Zinc phthalocyanine (ZnMintPc) into MWCNTs and GO, and the third phase, encapsulation in poly (N-vinylcaprolactam-co-poly(ethylene glycol diacrylate)) poly (VCL-co-PEGDA) polymer VCL/PEGDA a biocompatible hydrogel, to obtain the magnetic nanocomposites VCL/PEGDA-MNPs-MWCNTs-ZnMintPc and VCL/PEGDA-MNPs-GO-ZnMintPc. In vitro studies were carried out using Escherichia coli and Staphylococcus aureus bacteria and the Candida albicans yeast based on the Photodynamic/Photothermal (PTT/PDT) effect. This research describes the nanocomposites' optical, morphological, magnetic, and photophysical characteristics and their application as antimicrobial agents. The antimicrobial effect of magnetics nanocomposites was evaluated based on the PDT/PTT effect. For this purpose, doses of 65 mW·cm-2 with 630 nm light were used. The VCL/PEGDA-MNPs-GO-ZnMintPc nanocomposite eliminated E. coli and S. aureus colonies, while the VCL/PEGDA-MNPs-MWCNTs-ZnMintPc nanocomposite was able to kill the three types of microorganisms. Consequently, the latter is considered a broad-spectrum antimicrobial agent in PDT and PTT.

Vibration or Transcutaneous Tibial Nerve Stimulation as a Treatment for Sexual Dysfunction in Women with Spinal Cord Injury: Study Protocol for a Randomized Clinical Trial.

BACKGROUND: Women with spinal cord injuries usually suffer from sexual dysfunction, such as alterations during arousal and an increase in the time to reach orgasm. However, little evidence has been found on its physiotherapeutic approach, as well as poor adherence to the latter. The aim of this study is to determine the effectiveness of two interventions to improve sexual dysfunction: the application of genital vibration and transcutaneous tibial nerve stimulation. METHODS: This is a randomized clinical trial that will recruit 54 women who, one year after a spinal cord injury, suffer from sexual dysfunction associated with the latter. The participants will be randomized to three groups: (a) intervention group 1 treated with transcutaneous tibial nerve electrostimulation (n = 18), (b) intervention group 2 treated with genital vibration (n = 18), and (c) a control group (n = 18). The treatment time will be 12 weeks. Adherence to the treatment will be evaluated, as well as the effectiveness of the treatment, through the Female Sexual Function Index, the Sexual Quality of Life-Female questionnaire, quantitative sensory tests, and the improvement reported by the patient in terms of arousal and orgasm. The evaluations will be carried out before the treatment, at the end of the treatment and 3, 6 and 12 months after the end of the treatment.