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1.
Enferm Clin (Engl Ed) ; 34(2): 90-95, 2024.
Article in English | MEDLINE | ID: mdl-38484933

ABSTRACT

OBJECTIVE: Breast units led by nurse case managers are being implemented to provide comprehensive care in the detection and treatment of breast cancer. However, their implementation is heterogeneous and the results of the care process with this professional have not been studied. The aim of the study is to describe the management in time and the approach of the process by a nurse case manager in the breast unit of women with suspected breast cancer pathology, derived from the breast cancer screening program. METHODS: Descriptive, cross-sectional, retrospective study carried out in 2021. Women treated in a breast unit managed by a nurse case manager in a hospital in southern Spain were included. Sociodemographic, clinical and care process characteristics were analysed RESULTS: A total of 118 women of Spanish nationality (92%) participated, with a mean age of 59 years. The diagnosis of malignancy was made in 74.6% of them. Seventy-nine percent of the women had their first visit within 3 days. The mean time to diagnosis was 3.98 days (SD: ±3.93), 4.2 weeks (SD: ±1.84) to initiate treatment and a total in-hospital time of 33 days (SD: ±13.45). CONCLUSIONS: The management of nurse case managers in breast units contributes to improving or speeding up times, in accordance with international guidelines, helping this approach in the continuity of the care process for women referred after screening for breast cancer detection.


Subject(s)
Breast Neoplasms , Humans , Female , Cross-Sectional Studies , Retrospective Studies , Middle Aged , Breast Neoplasms/diagnosis , Breast Neoplasms/therapy , Breast Neoplasms/nursing , Case Managers , Case Management/organization & administration , Aged , Adult , Spain , Hospital Units
2.
Diagnostics (Basel) ; 14(6)2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38535021

ABSTRACT

Numerous papers report the efficiency of the automatic interpretation capabilities of commercial algorithms. Unfortunately, these algorithms are proprietary, and academia has no means of directly contributing to these results. In fact, nothing at the same stage of development exists in academia. Despite the extensive research in ECG signal processing, from signal conditioning to expert systems, a cohesive single application for clinical use is not ready yet. This is due to a serious lack of coordination in the academic efforts, which involve not only algorithms for signal processing, but also the signal acquisition equipment itself. For instance, the different sampling rates and the different noise levels frequently found in the available signal databases can cause severe incompatibility problems when the integration of different algorithms is desired. Therefore, this work aims to solve this incompatibility problem by providing the academic community with a diagnostic-grade electrocardiograph. The intention is to create a new standardized ECG signals database in order to address the automatic interpretation problem and create an electrocardiography system that can fully assist clinical practitioners, as the proprietary systems do. Achieving this objective is expected through an open and coordinated collaboration platform for which a webpage has already been created.

3.
Sensors (Basel) ; 24(2)2024 Jan 21.
Article in English | MEDLINE | ID: mdl-38276373

ABSTRACT

Early identification of respiratory irregularities is critical for improving lung health and reducing global mortality rates. The analysis of respiratory sounds plays a significant role in characterizing the respiratory system's condition and identifying abnormalities. The main contribution of this study is to investigate the performance when the input data, represented by cochleogram, is used to feed the Vision Transformer (ViT) architecture, since this input-classifier combination is the first time it has been applied to adventitious sound classification to our knowledge. Although ViT has shown promising results in audio classification tasks by applying self-attention to spectrogram patches, we extend this approach by applying the cochleogram, which captures specific spectro-temporal features of adventitious sounds. The proposed methodology is evaluated on the ICBHI dataset. We compare the classification performance of ViT with other state-of-the-art CNN approaches using spectrogram, Mel frequency cepstral coefficients, constant-Q transform, and cochleogram as input data. Our results confirm the superior classification performance combining cochleogram and ViT, highlighting the potential of ViT for reliable respiratory sound classification. This study contributes to the ongoing efforts in developing automatic intelligent techniques with the aim to significantly augment the speed and effectiveness of respiratory disease detection, thereby addressing a critical need in the medical field.


Subject(s)
Electric Power Supplies , Intelligence , Humans , Knowledge , Respiratory Rate , Respiratory Sounds/diagnosis
4.
Int J Mol Sci ; 24(17)2023 Aug 22.
Article in English | MEDLINE | ID: mdl-37685869

ABSTRACT

ITGAM-ITGAX (rs11150612, rs11574637), VAV3 rs17019602, CARD9 rs4077515, DEFA (rs2738048, rs10086568), and HORMAD2 rs2412971 are mucosal immune defence polymorphisms, that have an impact on IgA production, described as risk loci for IgA nephropathy (IgAN). Since IgAN and Immunoglobulin-A vasculitis (IgAV) share molecular mechanisms, with the aberrant deposit of IgA1 being the main pathophysiologic feature of both entities, we assessed the potential influence of the seven abovementioned polymorphisms on IgAV pathogenesis. These seven variants were genotyped in 381 Caucasian IgAV patients and 997 matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of these seven polymorphisms when the whole cohort of IgAV patients and those with nephritis were compared to controls. Similar genotype and allele frequencies of all polymorphisms were disclosed when IgAV patients were stratified according to the age at disease onset or the presence/absence of gastrointestinal or renal manifestations. Likewise, no ITGAM-ITGAX and DEFA haplotype differences were observed when the whole cohort of IgAV patients, along with those with nephritis and controls, as well as IgAV patients, stratified according to the abovementioned clinical characteristics, were compared. Our results suggest that mucosal immune defence polymorphisms do not represent novel genetic risk factors for IgAV pathogenesis.


Subject(s)
Glomerulonephritis, IGA , IgA Vasculitis , Immunity, Mucosal , Nephritis , Humans , CD11c Antigen , Gene Frequency , Genotype , Glomerulonephritis, IGA/genetics , IgA Vasculitis/genetics , Polymorphism, Genetic , Immunity, Mucosal/genetics
5.
Curr Med Chem ; 2023 Aug 18.
Article in English | MEDLINE | ID: mdl-37594106

ABSTRACT

BACKGROUND: Numerous biochemical reactions leading to altered cell proliferation cause tumorigenesis and cancer treatment resistance. The mechanisms implicated include genetic and epigenetic changes, modified intracellular signaling, and failure of control mechanisms caused by intrinsic and extrinsic factors alone or combined. No unique biochemical events are responsible; entangled molecular reactions conduct the resident cells in a tissue to display uncontrolled growth and abnormal migration. Copious experimental research supports the etiological responsibility of NK-1R (neurokinin-1 receptor) activation, alone or cooperating with other mechanisms, in cancer appearance in different tissues. Consequently, a profound study of this receptor system in the context of malignant processes is essential to design new treatments targeting NK-1R-deviated activity. METHOD: This study reviews and discusses recent literature that analyzes the main signaling pathways influenced by the activation of neurokinin 1 full and truncated receptor variants. Also, the involvement of NK-1R in cancer development is discussed. CONCLUSION: NK-1R can signal through numerous pathways and cross-talk with other receptor systems. The participation of override or malfunctioning NK-1R in malignant processes needs a more precise definition in different types of cancers to apply satisfactory and effective treatments. A long way has already been traveled: the current disposal of selective and effective NK-1R antagonists and the capacity to develop new drugs with biased agonistic properties based on the receptor's structural states with functional significance opens immediate research action and clinical application.

6.
Alerta (San Salvador) ; 6(2): 149-156, jul. 19, 2023. tab.
Article in Spanish | BISSAL, LILACS | ID: biblio-1442688

ABSTRACT

Las trampas extracelulares de neutrófilos (NET, por sus siglas en inglés) han surgido recientemente como un vínculo potencial entre la inmunidad y la inflamación, que podría cumplir un papel clave en la patogénesis de las infecciones de vías respiratorias. El objetivo de esta revisión es determinar su rol como marcador pronóstico en enfermedades infecciosas de vías respiratorias. Para la elaboración de este artículo de revisión narrativa se consultaron las publicaciones disponibles a través de una búsqueda automatizada en las bases de datos de PubMed, Scopus y Embase. Las concentraciones elevadas de trampas extracelulares de neutrófilos (cfADN, complejos de mieloperoxidasas-ADN) en pacientes con cuadro clínico grave por infecciones de vías respiratorias, se relacionan con una estancia hospitalaria más larga, periodo prolongado de administración de antibióticos, aumento del riesgo de ingreso a la UCI, necesidad de ventilación mecánica, disfunción orgánica e incluso la muerte (p ≤ 0,05). A pesar de no contar con un parámetro de medición estandarizado, el exceso de trampas extracelulares de neutrófilos se corresponde con la gravedad del daño tisular observado en pacientes con infecciones de vías respiratorias, esto revela el importante rol pronóstico de la respuesta de los neutrófilos y del proceso de la NETosis en las enfermedades infecciosas pulmonares


Neutrophil extracellular traps (NET) have recently emerged as a potential link between immunity and inflammation, which could play a key role in the pathogenesis of respiratory tract infections. This review aims to determine the role of neutrophil extracellular traps as prognostic markers in respiratoria tract infectious diseases. For this article a literature review was undertaken, consulting available publications through an automated search in PubMed, Scopus, and Embase databases. High concentrations of neutrophil extracellular traps (cfDNA, Myeloperoxidase-DNA complexes) in patients with severe clinical presentation due to respiratory tract infections are related to a longer length of hospital stay, prolonged period of antibiotic administration and increased risk of admission to the ICU, need for mechanical ventilation, organ dysfunction and even death (p ≤ 0.05). Despite not having a standardized measurement parameter, the excess of neutrophil extracellular traps corresponds to the severity of tissue damage observed in patients with respiratory tract infections, revealing the important prognostic role of the neutrophil response and NETosis process in pulmonary infectious diseases


Subject(s)
El Salvador
7.
Sensors (Basel) ; 23(9)2023 May 07.
Article in English | MEDLINE | ID: mdl-37177757

ABSTRACT

The work carried out in this paper consists of the classification of the physiological signal generated by eye movement called Electrooculography (EOG). The human eye performs simultaneous movements, when focusing on an object, generating a potential change in origin between the retinal epithelium and the cornea and modeling the eyeball as a dipole with a positive and negative hemisphere. Supervised learning algorithms were implemented to classify five eye movements; left, right, down, up and blink. Wavelet Transform was used to obtain information in the frequency domain characterizing the EOG signal with a bandwidth of 0.5 to 50 Hz; training results were obtained with the implementation of K-Nearest Neighbor (KNN) 69.4%, a Support Vector Machine (SVM) of 76.9% and Decision Tree (DT) 60.5%, checking the accuracy through the Jaccard index and other metrics such as the confusion matrix and ROC (Receiver Operating Characteristic) curve. As a result, the best classifier for this application was the SVM with Jaccard Index.


Subject(s)
Algorithms , Support Vector Machine , Humans , Electrooculography/methods , Eye Movements , Wavelet Analysis
8.
Int J Mol Sci ; 24(8)2023 Apr 13.
Article in English | MEDLINE | ID: mdl-37108375

ABSTRACT

Celiac disease (CeD) is an immune-mediated disorder triggered by gluten ingestion that damages the small intestine. Although CeD has been associated with a higher risk for cancer, the role of CeD as a risk factor for specific malignancies, such as enteropathy-associated T-cell lymphoma (EATL), remains controversial. Using two-sample Mendelian randomization (2SMR) methods and the summarized results of large genome-wide association studies from public repositories, we addressed the causal relationship between CeD and eight different malignancies. Eleven non-HLA SNPs were selected as instrumental variables (IVs), and causality estimates were obtained using four 2SMR methods: random-effects inverse variance-weighted, weighted median estimation, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO). We identified a significant causal relationship between CeD and mature T/NK cell lymphomas. Under a multivariate Mendelian randomization model, we observed that the causal effect of CeD was not dependent on other known lymphoma risk factors. We found that the most instrumental IV was located in the TAGAP locus, suggesting that aberrant T cell activation might be relevant in the T/NK cell malignization process. Our findings provide new insights into the connection between immune imbalance and the development of severe comorbidities, such as EATL, in patients with CeD.


Subject(s)
Celiac Disease , Lymphoma , Humans , Celiac Disease/genetics , Genome-Wide Association Study , Mendelian Randomization Analysis , Killer Cells, Natural , Risk Factors , Polymorphism, Single Nucleotide
11.
Ann Rheum Dis ; 82(6): 837-847, 2023 06.
Article in English | MEDLINE | ID: mdl-36797040

ABSTRACT

OBJECTIVES: The number of susceptibility loci currently associated with vasculitis is lower than in other immune-mediated diseases due in part to small cohort sizes, a consequence of the low prevalence of vasculitides. This study aimed to identify new genetic risk loci for the main systemic vasculitides through a comprehensive analysis of their genetic overlap. METHODS: Genome-wide data from 8467 patients with any of the main forms of vasculitis and 29 795 healthy controls were meta-analysed using ASSET. Pleiotropic variants were functionally annotated and linked to their target genes. Prioritised genes were queried in DrugBank to identify potentially repositionable drugs for the treatment of vasculitis. RESULTS: Sixteen variants were independently associated with two or more vasculitides, 15 of them representing new shared risk loci. Two of these pleiotropic signals, located close to CTLA4 and CPLX1, emerged as novel genetic risk loci in vasculitis. Most of these polymorphisms appeared to affect vasculitis by regulating gene expression. In this regard, for some of these common signals, potential causal genes were prioritised based on functional annotation, including CTLA4, RNF145, IL12B, IL5, IRF1, IFNGR1, PTK2B, TRIM35, EGR2 and ETS2, each of which has key roles in inflammation. In addition, drug repositioning analysis showed that several drugs, including abatacept and ustekinumab, could be potentially repurposed in the management of the analysed vasculitides. CONCLUSIONS: We identified new shared risk loci with functional impact in vasculitis and pinpointed potential causal genes, some of which could represent promising targets for the treatment of vasculitis.


Subject(s)
Systemic Vasculitis , Vasculitis , Humans , CTLA-4 Antigen , Drug Repositioning , Genetic Predisposition to Disease/genetics , Systemic Vasculitis/genetics , Vasculitis/drug therapy , Vasculitis/genetics , Apoptosis Regulatory Proteins/genetics
12.
Healthcare (Basel) ; 11(2)2023 Jan 13.
Article in English | MEDLINE | ID: mdl-36673617

ABSTRACT

Introduction (1): The COVID-19 pandemic led to changes in healthcare during pregnancy, childbirth and puerperium. The objective of this study was to know the impact of visit restrictions, PCR performance and use of masks on delivery and puerperium care. Methods (2): A descriptive cross-sectional study was carried out. A survey was used to assess the impact of COVID-19-related measures on women who had given birth in hospitals in the Region of Murcia, Spain, between March 2020 and February 2022. Results (3): The final sample size was 434 women. The average scores were 4.27 for dimension 1 (Visit restrictions), 4.15 for dimension 2 (PCR testing) and 3.98 for dimension 3 (Mask use). More specifically, we found that the restriction of visits was considered a positive measure for the establishment of the mother-newborn bond (mean score 4.37) and that the use of masks at the time of delivery should have been made more flexible (mean score 4.7). Conclusions (4): The policy of restricting hospital visits during the pandemic caused by COVID-19 has been considered beneficial by mothers, who expressed that they did not feel lonely during their hospital stay.

13.
Sci Adv ; 8(29): eabo6406, 2022 07 22.
Article in English | MEDLINE | ID: mdl-35857843

ABSTRACT

Hepatocellular carcinoma (HCC) develops predominantly in the inflammatory environment of a cirrhotic liver caused by hepatitis, toxin exposure, or chronic liver disease. A targeted therapeutic approach is required to enable cancer killing without causing toxicity and liver failure. Poly(beta-amino-ester) (PBAE) nanoparticles (NPs) were used to deliver a completely CpG-free plasmid harboring mutant herpes simplex virus type 1 sr39 thymidine kinase (sr39) DNA to human HCC cells. Transfection with sr39 enables cancer cell killing with the prodrug ganciclovir and accumulation of 9-(4-18F-fluoro-3-hydroxymethylbutyl)guanine (18F-FHBG) for in vivo imaging. Targeting was achieved using a CpG-free human alpha fetoprotein (AFP) promoter (CpGf-AFP-sr39). Expression was restricted to AFP-producing HCC cells, enabling selective transfection of orthotopic HCC xenografts. CpGf-AFP-sr39 NP treatment resulted in 62% reduced tumor size, and therapeutic gene expression was detectable by positron emission tomography (PET). This systemic nanomedicine achieved tumor-specific delivery, therapy, and imaging, representing a promising platform for targeted treatment of HCC.


Subject(s)
Carcinoma, Hepatocellular , Herpesvirus 1, Human , Liver Neoplasms , Nanoparticles , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , Cell Line, Tumor , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Polymers , Precision Medicine , alpha-Fetoproteins/genetics
14.
Andrology ; 10(7): 1339-1350, 2022 10.
Article in English | MEDLINE | ID: mdl-35752927

ABSTRACT

BACKGROUND: Previous studies in animal models evidenced that genetic mutations of KATNAL1, resulting in dysfunction of its encoded protein, lead to male infertility through disruption of microtubule remodelling and premature germ cell exfoliation. Subsequent studies in humans also suggested a possible role of KATNAL1 single-nucleotide polymorphisms in the development of male infertility as a consequence of severe spermatogenic failure. OBJECTIVES: The main objective of the present study is to evaluate the effect of the common genetic variation of KATNAL1 in a large and phenotypically well-characterised cohort of infertile men because of severe spermatogenic failure. MATERIALS AND METHODS: A total of 715 infertile men because of severe spermatogenic failure, including 210 severe oligospermia and 505 non-obstructive azoospermia patients, as well as 1058 unaffected controls were genotyped for three KATNAL1 single-nucleotide polymorphism taggers (rs2077011, rs7338931 and rs2149971). Case-control association analyses by logistic regression assuming different models and in silico functional characterisation of risk variants were conducted. RESULTS: Genetic associations were observed between the three analysed taggers and different severe spermatogenic failure groups. However, in all cases, the haplotype model (rs2077011*C | rs7338931*T | rs2149971*A) better explained the observed associations than the three risk alleles independently. This haplotype was associated with non-obstructive azoospermia (adjusted p = 4.96E-02, odds ratio = 2.97), Sertoli-cell only syndrome (adjusted p = 2.83E-02, odds ratio = 5.16) and testicular sperm extraction unsuccessful outcomes (adjusted p = 8.99E-04, odds ratio = 6.13). The in silico analyses indicated that the effect on severe spermatogenic failure predisposition could be because of an alteration of the KATNAL1 splicing pattern. CONCLUSIONS: Specific allelic combinations of KATNAL1 genetic polymorphisms may confer a risk of developing severe male infertility phenotypes by favouring the overrepresentation of a short non-functional transcript isoform in the testis.


Subject(s)
Azoospermia , Infertility, Male , Katanin , Oligospermia , Animals , Humans , Male , Azoospermia/genetics , Infertility, Male/genetics , Katanin/genetics , Oligospermia/genetics , Phenotype , Polymorphism, Single Nucleotide , Protein Isoforms/genetics , Semen , Spermatogenesis/genetics
15.
Sci Immunol ; 7(72): eabf1861, 2022 06 24.
Article in English | MEDLINE | ID: mdl-35714202

ABSTRACT

The gastrointestinal (GI) tract constitutes an essential barrier against ingested microbes, including potential pathogens. Although immune reactions are well studied in the lower GI tract, it remains unclear how adaptive immune responses are initiated during microbial challenge of the oral mucosa (OM), the primary site of microbial encounter in the upper GI tract. Here, we identify mandibular lymph nodes (mandLNs) as sentinel lymphoid organs that intercept ingested Listeria monocytogenes (Lm). Oral Lm uptake led to local activation and release of antigen-specific CD8+ T cells that constituted most of the early circulating effector T cell (TEFF) pool. MandLN-primed TEFF disseminated to lymphoid organs, lung, and OM and contributed substantially to rapid elimination of target cells. In contrast to CD8+ TEFF generated in mesenteric LN (MLN) during intragastric infection, mandLN-primed TEFF lacked a gut-seeking phenotype, which correlated with low expression of enzymes required for gut-homing imprinting by mandLN stromal and dendritic cells. Accordingly, mandLN-primed TEFF decreased Lm burden in spleen but not MLN after intestinal infection. Our findings extend the concept of regional specialization of immune responses along the length of the GI tract, with CD8+ TEFF generated in the upper GI tract displaying homing profiles that differ from those imprinted by lymphoid tissue of the lower GI tract.


Subject(s)
CD8-Positive T-Lymphocytes , Mouth Mucosa , Lymph Nodes , Phenotype , T-Lymphocytes, Cytotoxic
16.
Exp Eye Res ; 219: 109061, 2022 06.
Article in English | MEDLINE | ID: mdl-35390333

ABSTRACT

The Tear Film Lipid Layer (TFLL) acts primarily as an interface between the aqueous layer and air. Tear film lipid is composed of a thin layer of polar lipids that interact with the secretory layer of the underlying mucosa and a thicker layer of non-polar lipids at the air interface. The tear film has a complex structure and composition that protects the cornea, promotes wound healing, and maintains high-quality vision. Plasma Rich in Growth Factor (PRGF) eye drops emerged as an exciting new treatment for corneal epitheliopathies, including aqueous deficient dry eye. The purpose of this study was to compare the lipidomic profile of eye drops obtained from PRGF with tear lipidome to determine whether PRGF drops could be an adequate complement to tears in patients with impaired TFLL. To address this study, tears and blood was collected and processed from healthy donors to obtain PRGF eye drops. Samples were aliquoted and stored at -80 °C until use. The lipid profiles of these samples were analysed by Ultrahigh Performance Liquid Chromatography (UHPLC) using a Vanquish UHPLC system to obtain untargeted lipidome profiles on a Q-Exactive HF-X hybrid quadrupole-Orbitrap mass spectrometer. In PRGF eye drops, 408 lipids were identified in ESI+ mode and 183 in ESI- mode, and they were grouped into 15 different lipid classes from four distinct categories. By contrast, 112 lipid species were identified from tear samples in ESI+ mode and 36 in ESI- mode, belonging to 12 lipid classes from six different categories. The relative abundance of most lipid species was much greater in the PRGF eye drops than in the tear, although there were some lipids present in tears that were not found in the PRGF, such as wax esters and (O-acyl)-ω-hydroxy fatty acids. In summary, these results suggest that the lipids present in PRGF eye drops could serve as a tear supplement in individuals in whom tear lipid composition is altered, although there are differences in the lipid profile of these two fluids.


Subject(s)
Dry Eye Syndromes , Lipids , Dry Eye Syndromes/drug therapy , Humans , Intercellular Signaling Peptides and Proteins , Lipids/analysis , Ophthalmic Solutions , Tears/chemistry
17.
Plants (Basel) ; 11(3)2022 Jan 26.
Article in English | MEDLINE | ID: mdl-35161311

ABSTRACT

Androgenetic alopecia (AGA), a hair loss disorder, is a genetic predisposition to sensitive androgens, inflammation, and oxidative stress. Unfortunately, current treatments with synthetic medicines contain a restricted mechanism along with side effects, whereas the bioactive constituents of plant extracts are multifunctional, with fewer side effects. The massive amounts of rice husk and bran are agricultural wastes that may cause pollution and environmental problems. Owing to these rationales, the local rice variety, Bue Bang 3 CMU (BB3CMU), which is grown in northern Thailand, was evaluated for the valuable utilization of rice by-products, husk (BB3CMU-H) and bran (BB3CMU-RB) extracts, for AGA treatment regarding antioxidant, anti-inflammatory, anti-androgenic activities, and the characterization of bioactive compounds. Our study verified that BB3CMU-H had the highest level of polyphenols, contributing to its greater antioxidant activity. Conversely, BB3CMU-RB was the predominant source of tocopherols, resulting in better anti-androgenic activities regarding the downregulation of steroid 5α-reductase genes (SRD5A). Notably, anti-inflammation via the attenuation of nitric oxide productions was observed in BB3CMU-H (0.06 ± 0.13 µM) and BB3CMU-RB (0.13 ± 0.01 µM), which were significantly comparable to diclofenac sodium salt (0.13 ± 0.19 µM). Therefore, the combination of BB3CMU-H and BB3CMU-RB could be utilized in cosmeceutical and pharmaceutical applications for AGA patients.

18.
Eur J Immunol ; 52(1): 161-177, 2022 01.
Article in English | MEDLINE | ID: mdl-34524684

ABSTRACT

The migration of CD4+ effector/memory T cells across the blood-brain barrier (BBB) is a critical step in MS or its animal model, EAE. T-cell diapedesis across the BBB can occur paracellular, via the complex BBB tight junctions or transcellular via a pore through the brain endothelial cell body. Making use of primary mouse brain microvascular endothelial cells (pMBMECs) as in vitro model of the BBB, we here directly compared the transcriptome profile of pMBMECs favoring transcellular or paracellular T-cell diapedesis by RNA sequencing (RNA-seq). We identified the atypical chemokine receptor 1 (Ackr1) as one of the main candidate genes upregulated in pMBMECs favoring transcellular T-cell diapedesis. We confirmed upregulation of ACKR1 protein in pMBMECs promoting transcellular T-cell diapedesis and in venular endothelial cells in the CNS during EAE. Lack of endothelial ACKR1 reduced transcellular T-cell diapedesis across pMBMECs under physiological flow in vitro. Combining our previous observation that endothelial ACKR1 contributes to EAE pathogenesis by shuttling chemokines across the BBB, the present data support that ACKR1 mediated chemokine shuttling enhances transcellular T-cell diapedesis across the BBB during autoimmune neuroinflammation.


Subject(s)
Blood-Brain Barrier , CD4-Positive T-Lymphocytes , Duffy Blood-Group System , Encephalomyelitis, Autoimmune, Experimental , Memory T Cells , Multiple Sclerosis , Receptors, Cell Surface , Transendothelial and Transepithelial Migration , Animals , Mice , Blood-Brain Barrier/immunology , CD4-Positive T-Lymphocytes/immunology , Duffy Blood-Group System/genetics , Duffy Blood-Group System/immunology , Encephalomyelitis, Autoimmune, Experimental/genetics , Encephalomyelitis, Autoimmune, Experimental/immunology , Inflammation/genetics , Inflammation/immunology , Memory T Cells/immunology , Mice, Knockout , Multiple Sclerosis/genetics , Multiple Sclerosis/immunology , Receptors, Cell Surface/genetics , Receptors, Cell Surface/immunology , Transendothelial and Transepithelial Migration/genetics , Transendothelial and Transepithelial Migration/immunology
19.
Sensors (Basel) ; 21(17)2021 Aug 31.
Article in English | MEDLINE | ID: mdl-34502773

ABSTRACT

People with severe disabilities require assistance to perform their routine activities; a Human-Machine Interface (HMI) will allow them to activate devices that respond according to their needs. In this work, an HMI based on electrooculography (EOG) is presented, the instrumentation is placed on portable glasses that have the task of acquiring both horizontal and vertical EOG signals. The registration of each eye movement is identified by a class and categorized using the one hot encoding technique to test precision and sensitivity of different machine learning classification algorithms capable of identifying new data from the eye registration; the algorithm allows to discriminate blinks in order not to disturb the acquisition of the eyeball position commands. The implementation of the classifier consists of the control of a three-wheeled omnidirectional robot to validate the response of the interface. This work proposes the classification of signals in real time and the customization of the interface, minimizing the user's learning curve. Preliminary results showed that it is possible to generate trajectories to control an omnidirectional robot to implement in the future assistance system to control position through gaze orientation.


Subject(s)
Robotics , Algorithms , Electrooculography , Eye Movements , Humans , Machine Learning
20.
Int Arch Allergy Immunol ; 182(12): 1226-1230, 2021.
Article in English | MEDLINE | ID: mdl-34392241

ABSTRACT

BACKGROUND: As the number of allergic sensitizations increases the severity of allergic respiratory diseases worsens. Multiple monoallergen immunotherapy can be accompanied by poor treatment adherence and high costs, single multiallergen immunotherapy needs to prove efficacy whilst maintaining a good safety profile. METHODS: Observational, retrospective, multicenter study using a 2-pollen single undiluted multiallergen subcutaneous immunotherapy (SCIT) in routine clinical practice in Spain. Patients with rhinoconjunctivitis, with/without controlled asthma, sensitized to grass, olive, Parietaria, Cupressus, plane tree and/or Salsola pollen were included. Primary and secondary clinical efficacy endpoints were quality of life (mini Rhinitis Quality of Life Questionnaire (miniRQLQ)) and visual analogue scale (VAS) respectively. All adverse events were documented. RESULTS: Ten centers included 97 patients, median age 32 years. SCIT treatment included combinations of grass mix with olive, Parietaria, Cupressus, plane tree or Salsola or olive with Parietaria, Cupressus or Salsola. The mean duration of SCIT was 1.8 years with a high treatment adherence (73%). Significant improvement in quality of life, nasal and ocular symptoms, activity limitations and practical problems (p< 0.0001) and other symptoms (p= 0.024) was observed. Most patients did not develop asthma-like symptoms and a significant improvement of all allergic symptom severity was perceived. VAS showed a significant improvement in rhinoconjunctivitis and asthma by patients and physicians. Twenty-nine patients experienced adverse reactions, 25 had local and 6 had systemic reactions. CONCLUSIONS: Single undiluted multiallergen SCIT treatment of two different pollens is efficacious and safe in both children and adults, showing that it is a suitable option for the treatment of polyallergic patients.


Subject(s)
Allergens/therapeutic use , Conjunctivitis, Allergic/therapy , Desensitization, Immunologic/methods , Pollen/immunology , Rhinitis, Allergic/therapy , Adolescent , Adult , Aged , Allergens/immunology , Child , Conjunctivitis, Allergic/immunology , Female , Humans , Injections, Subcutaneous , Male , Middle Aged , Patient Acuity , Quality of Life , Retrospective Studies , Rhinitis, Allergic/immunology , Treatment Outcome , Young Adult
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