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1.
medRxiv ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39252931

RESUMEN

Background Clonal complex 180 (CC180) is currently the major clone of serotype 3 Streptococcus pneumoniae (Spn). The 13-valent pneumococcal conjugate vaccine (PCV13) does not have significant efficacy against serotype 3 despite polysaccharide inclusion in the vaccine. It was hypothesized that PCV13 may effectively control Clade I of CC180 but that Clades III and IV are resistant, provoking a population shift that enables serotype 3 persistence. This has been observed in the United States, England, and Wales but not Spain. We tested this hypothesis further utilizing a dataset from Portugal. Methods We whole-genome sequenced (WGS) 501 serotype 3 strains from Portugal isolated from patients with pneumococcal infections between 1999-2020. The draft genomes underwent phylogenetic analyses, pangenome profiling, and a genome-wide association study (GWAS). We also completed antibiotic susceptibility testing and compiled over 2,600 serotype 3 multilocus sequence type 180 (MLST180) WGSs to perform global comparative genomics. Findings CC180 Clades I, II, III, IV, and VI distributions were similar when comparing non-invasive pneumonia isolates and invasive disease isolates (Fisher's exact test, P=0.29), and adult and pediatric cases (Fisher's exact test, P=0.074). The serotype 3 CCs shifted post-PCV13 (Fisher's exact test, P<0.0001) and Clade I became dominant. Clade I is largely antibiotic-sensitive and carries the phiOXC141 prophage but the pangenome is heterogenous. Strains from Portugal and Spain, where Clade I remains dominant post-PCV13, have larger pangenomes and are associated with the presence of two genes encoding hypothetical proteins. Interpretation Clade I became dominant in Portugal post-PCV13, despite the burden of the prophage and antibiotic sensitivity. The accessory genome content may mitigate these fitness costs. Regional differences in Clade I prevalence and pangenome heterogeneity suggest that clade dynamics is not a generalizable approach to understanding serotype 3 vaccine escape. Funding National Institute of Child Health and Human Development, Pfizer, and Merck Sharp & Dohme.

2.
Osteoarthr Cartil Open ; 6(3): 100509, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39224132

RESUMEN

T1 ρ and Quantitative Susceptibility Mapping (QSM) are evolving as substrates for quantifying the progressive nature of knee osteoarthritis. Objective: To evaluate the effects of spin lock time combinations on depth-dependent T1 ρ estimation, in adjunct to QSM, and characterize the degree of shared variance in QSM and T1 ρ for the quantitative measurement of articular cartilage. Design: Twenty healthy participants (10 â€‹M/10F, 22.2 â€‹± â€‹3.4 years) underwent bilateral knee MRI using T1 ρ MAPPS sequences with varying TSLs ([0-120] ms), along with a 3D spoiled gradient echo for QSM. Five total TSL combinations were used for T1 ρ computation, and direct depth-based comparison. Depth-wide variance was assessed in comparison to QSM as a basis to assess for depth-specific variation in T1 ρ computations across healthy cartilage. Results: Longer T1 ρ relaxation times were observed for TSL combinations with higher spin lock times. Depth-specific differences were documented for both QSM and T1 ρ , with most change found at ∼60% depth of the cartilage, relative to the surface. Direct squared linear correlation revealed that most T1 ρ TSL combinations can explain over 30% of the variability in QSM, suggesting inherent shared sensitivity to cartilage microstructure. Conclusions: T1 ρ mapping is subjective to the spin lock time combinations used for computation of relaxation times. When paired with QSM, both similarities and differences in signal sensitivity may be complementary to capture depth-wide changes in articular cartilage.

3.
Expert Rev Anti Infect Ther ; : 1-15, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39269198

RESUMEN

INTRODUCTION: The human respiratory syncytial virus (hRSV) is one of childhood diseases' most common respiratory pathogens and is associated with lower respiratory tract infections. The peak in disease that this virus can elicit during outbreaks is often a significant burden for healthcare systems worldwide. Despite theapproval of treatments against hRSV, this pathogen remains one the most common causative agent of infant mortality around the world. AREAS COVERED: This review focuses on the key prognostic and immunomodulatory biomarkers associated with hRSV infection, as well as prophylactic monoclonal antibodies and vaccines. The goal is to catalyze a paradigm shift within the scientific community toward the discovery of novel targets to predict the clinical outcome of infected patients, as well as the development of novel antiviral agents targeting hRSV. The most pertinent research on this topic was systematically searched and analyzed using PubMed ISI Thomson Scientific databases. EXPERT OPINION: Despite advances in approved therapies against hRSV, it is crucial to continue researching to develop new therapies and to find specific biomarkers to predict the severity of infection. Along these lines, the use of multi-omics data, artificial intelligence and natural-derived compounds with antiviral activity could be evaluated to fight hRSV and develop methods for rapid diagnosis of severity.

4.
J Clin Med ; 13(17)2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39274431

RESUMEN

Urinary tract infections (UTIs) constitute one of the main complications in kidney recipients, increasing both morbidity and mortality. Due to the resurgence of antimicrobial resistance, new prophylactic approaches are being investigated. Nitrofurantoin is an antibiotic from the nitrofuran group that is effective against several Gram-negative and Gram-positive organisms; hence, there has been a resurgence in its prescription for treating MDR pathogens. Objectives: This study aims to assess the effectiveness of nitrofurantoin as an add-on to conventional therapy (amikacin + ceftriaxone or cefotaxime) for the treatment of urinary tract infections in kidney recipients. Methods: In a prospective cohort study, we included patients who received a kidney in a tertiary-care hospital. According to the intensive care specialist, group 1 patients were treated with the conventional prophylactic treatment plus nitrofurantoin as an add-on. Group 2 patients were treated only with the conventional prophylactic treatment. They were followed-up for 3 months, and the incidence of urinary tract infections was reported. Results: The UTI incidence for group 1 at 3 months was 20.6%, and for group 2, it was 20.0%; no statistical difference between treatments was observed (p = 0.9). The most commonly isolated pathogens were E. coli (28.5) and K. pneumonie (28.5%). The factor most associated with developing a UTI was female gender (aHR: 7.0; 95% IC 2.3-20.9, p < 0.001). Conclusions: In our cohort study, nitrofurantoin as an add-on in conventional therapy did not prove to be effective in preventing UTI development; therefore, other treatment options should be considered as a part of prophylactic treatment.

5.
J Infect ; 89(4): 106242, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39116949

RESUMEN

OBJECTIVES: The COVID-19 pandemic led to the institution of public health measures in many countries which reduced respiratory infections. We aimed to identify and characterize changes in pediatric (<18 years) invasive pneumococcal disease (pIPD) in Portugal in 2018-2023. METHODS: pIPD cases were identified by culture and molecular methods and stratified by age and serotype. When available the susceptibility of the isolates to antimicrobials was evaluated. RESULTS: pIPD cases were markedly reduced in the last trimester of 2019-2020 and the entire 2020-2021 season. While 2021-2022 was in line with pre-pandemic seasons, in 2022-2023, the number of pIPD cases exceeded those found pre-pandemic. Molecular tests were responsible for identifying and serotyping 30% of cases, highlighting their importance in evaluating pIPD. Among the 316 pIPD cases, 37 different serotypes were detected, of which serotypes 3 (n = 85, 26.9%), 8 (n = 25, 7.9%), 10A (n = 21, 6.6%) and 24F (n = 20, 6.3%) were the most frequent. The post-pandemic serotype distribution reflected mostly pre-pandemic trends and the rebound was not driven by particular serotypes. We identified many vaccine failures, most (n = 37) representing serotype 3 infections. Penicillin non-susceptibility increased from 14% pre-pandemic to 29%, with serotype 24F becoming particularly significant. CONCLUSIONS: The higher number of cases of pIPD post-COVID-19 in Portugal raises the possibility of a higher burden of pneumococcal disease in Europe post-pandemic. The relatively stable serotype distribution and the current availability of the higher valency conjugate vaccines PCV15 and PCV20, potentially preventing a large proportion of pIPD (43% and 67%, respectively), offer an opportunity to control this increase.


Asunto(s)
COVID-19 , Infecciones Neumocócicas , Vacunas Neumococicas , Serogrupo , Streptococcus pneumoniae , Humanos , Portugal/epidemiología , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/microbiología , COVID-19/epidemiología , Niño , Preescolar , Streptococcus pneumoniae/clasificación , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/aislamiento & purificación , Lactante , Adolescente , Femenino , Masculino , Vacunas Neumococicas/administración & dosificación , Recién Nacido , Serotipificación , SARS-CoV-2 , Pandemias , Antibacterianos/farmacología , Antibacterianos/uso terapéutico
6.
Vaccine ; 42(23): 126203, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39178767

RESUMEN

SARS-CoV-2 is the causative virus of COVID-19, which has been responsible for millions of deaths worldwide since its discovery. After its emergence, several variants have been identified that challenge the efficacy of the available vaccines. Previously, we generated and evaluated a vaccine based on a recombinant Bacillus Calmette-Guérin (rBCG) expressing the nucleoprotein (N) of SARS-CoV-2 (rBCG-N-SARS-CoV-2). This protein is a highly immunogenic antigen and well conserved among variants. Here, we tested the administration of this vaccine with recombinant N and viral Spike proteins (S), or Receptor Binding Domain (RBD-Omicron variant), plus a booster with the recombinant proteins only, as a novel and effective strategy to protect against SARS-CoV-2 variants. METHODS: BALB/c mice were immunized with rBCG-N-SARS-CoV-2 and recombinant SARS-CoV-2 proteins in Alum adjuvant, followed by a booster with recombinant proteins to assess the safety and virus-specific cellular and humoral immune responses against SARS-CoV-2 antigens. RESULTS: Immunization with rBCG-N-SARS-CoV-2 + recombinant proteins as a vaccine was safe and promoted the activation of CD4+ and CD8+ T cells that recognize SARS-CoV-2 N, S, and RBD antigens. These cells were able to secrete cytokines with an antiviral profile. This immunization strategy also induced robust titers of specific antibodies against N, S, and RBD and neutralizing antibodies of SARS-CoV-2. CONCLUSIONS: Co-administration of the rBCG-N-SARS-CoV-2 vaccine with recombinant SARS-CoV-2 proteins could be an effective alternative to control particular SARS-CoV-2 variants. Due to its safety and capacity to induce virus-specific immune responses, we believe the rBCG-N-SARS-CoV-2 + Proteins vaccine could be an attractive candidate to protect against this virus, especially in newborns.


Asunto(s)
Anticuerpos Antivirales , Vacuna BCG , Vacunas contra la COVID-19 , COVID-19 , Ratones Endogámicos BALB C , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Animales , Ratones , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , COVID-19/prevención & control , COVID-19/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Vacuna BCG/inmunología , Vacuna BCG/administración & dosificación , Vacuna BCG/genética , Femenino , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Inmunización Secundaria , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Inmunidad Humoral , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/genética , Proteínas de la Nucleocápside de Coronavirus/inmunología , Proteínas de la Nucleocápside de Coronavirus/genética , Linfocitos T CD8-positivos/inmunología , Fosfoproteínas/inmunología , Fosfoproteínas/genética , Adyuvantes Inmunológicos/administración & dosificación , Inmunidad Celular
7.
Immunology ; 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39161170

RESUMEN

Acute respiratory infections are the leading cause of death and illness in children under 5 years old and represent a significant burden in older adults. Primarily caused by viruses infecting the lower respiratory tract, symptoms include cough, congestion, and low-grade fever, potentially leading to bronchiolitis and pneumonia. Messenger ribonucleic acid (mRNA)-based vaccines are biopharmaceutical formulations that employ mRNA molecules to induce specific immune responses, facilitating the expression of viral or bacterial antigens and promoting immunization against infectious diseases. Notably, this technology had significant relevance during the COVID-19 pandemic, as these formulations helped to limit SARS-CoV-2 virus infections, hospitalizations, and deaths. Importantly, mRNA vaccines promise to be implemented as new alternatives for fighting other respiratory viruses, such as influenza, human respiratory syncytial virus, and human metapneumovirus. This review article analyzes mRNA-based vaccines' main contributions, perspectives, challenges, and implications against respiratory viruses.

8.
PeerJ ; 12: e17673, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39131622

RESUMEN

Whole genome sequencing (WGS) has become a vital tool in clinical microbiology, playing an important role in outbreak investigations, molecular surveillance, and identification of bacterial species, resistance mechanisms and virulence factors. However, the complexity of WGS data presents challenges in interpretation and reporting, requiring tailored strategies to enhance efficiency and impact. This study explores the diverse needs of key stakeholders in healthcare, including clinical management, laboratory work, public surveillance and epidemiology, infection prevention and control, and academic research, regarding WGS-based reporting of clinically relevant bacterial species. In order to determine preferences regarding WGS reports, human-centered design approach was employed, involving an online survey and a subsequent workshop with stakeholders. The survey gathered responses from 64 participants representing the above mentioned healthcare sectors across geographical regions. Key findings include the identification of barriers related to data accessibility, integration with patient records, and the complexity of interpreting WGS results. As the participants designed their ideal report using nine pre-defined sections of a typical WGS report, differences in needs regarding report structure and content across stakeholders became evident. The workshop discussions further highlighted the need to feature critical findings and quality metrics prominently in reports, as well as the demand for flexible report designs. Commonalities were observed across stakeholder-specific reporting templates, such as the uniform ranking of certain report sections, but preferences regarding the depth of content within these sections varied. Using these findings, we suggest stakeholder-specific structures which should be considered when designing customized reporting templates. In conclusion, this study underscores the importance of tailoring WGS-based reports of clinically relevant bacteria to meet the distinct needs of diverse healthcare stakeholders. The evolving landscape of digital reporting increases the opportunities with respect to WGS reporting and its utility in managing infectious diseases and public health surveillance.


Asunto(s)
Secuenciación Completa del Genoma , Humanos , Genoma Bacteriano/genética , Encuestas y Cuestionarios
10.
Int J Mol Sci ; 25(12)2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38928446

RESUMEN

Multiple sclerosis (MS) is a common disease in young women of reproductive age, characterized by demyelination of the central nervous system (CNS). Understanding how genes related to MS are expressed during pregnancy can provide insights into the potential mechanisms by which pregnancy affects the course of this disease. This review article presents evidence-based studies on these patients' gene expression patterns. In addition, it constructs interaction networks using bioinformatics tools, such as STRING and KEGG pathways, to understand the molecular role of each of these genes. Bioinformatics research identified 25 genes and 21 signaling pathways, which allows us to understand pregnancy patients' genetic and biological phenomena and formulate new questions about MS during pregnancy.


Asunto(s)
Biología Computacional , Esclerosis Múltiple , Humanos , Esclerosis Múltiple/genética , Esclerosis Múltiple/metabolismo , Femenino , Embarazo , Biología Computacional/métodos , Redes Reguladoras de Genes , Complicaciones del Embarazo/genética , Complicaciones del Embarazo/metabolismo , Perfilación de la Expresión Génica , Transducción de Señal/genética , Regulación de la Expresión Génica
11.
Mol Phylogenet Evol ; 197: 108083, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38679303

RESUMEN

Kinosternon is the most speciose genus of extant turtles, with 22 currently recognized species, distributed across large parts of the Americas. Most species have small distributions, but K. leucostomum and K. scorpioides range from Mexico to South America. Previous studies have found discordance between mitochondrial and nuclear phylogenies in some kinosternid groups, with the current taxonomy following the nuclear-based results. Herein, based on extended molecular, geographic, and taxonomic sampling, we explore the phylogeographic structure and taxonomic limits for K. leucostomum and the K. scorpioides group and present a fossil-calibrated nuclear time tree for Kinosternon. Our results reveal contrasting differentiation patterns for the K. scorpioides group and K. leucostomum, despite overlapping distributions. Kinosternon leucostomum shows only shallow geographic divergence, whereas the K. scorpioides group is polyphyletic with up to 10 distinct taxa, some of them undescribed. We support the elevation of K. s. albogulare and K. s. cruentatum to species level. Given the deep divergence within the genus Kinosternon, we propose the recognition of three subgenera, Kinosternon, Cryptochelys and Thyrosternum, and the abandonment of the group-based classification, at least for the K. leucostomum and K. scorpioides groups. Our results show an initial split in Kinosternon that gave rise to two main radiations, one Nearctic and one mainly Neotropical. Most speciation events in Kinosternon occurred during the Quaternary and we hypothesize that they were mediated by both climatic and geological events. Additionally, our data imply that at least three South American colonizations occurred, two in the K. leucostomum group, and one in the K. scorpioides group. Additionally, we hypothesize that discordance between mitochondrial and nuclear phylogenetic signal is due to mitochondrial capture from an extinct kinosternine lineage.


Asunto(s)
Filogenia , Filogeografía , Tortugas , Animales , Tortugas/clasificación , Tortugas/genética , América del Sur , Núcleo Celular/genética , ADN Mitocondrial/genética , Análisis de Secuencia de ADN , Tipificación de Secuencias Multilocus , Variación Genética , Teorema de Bayes
12.
Nat Commun ; 15(1): 2286, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38480728

RESUMEN

Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging cause of human infection with invasive disease incidence and clinical manifestations comparable to the closely related species, Streptococcus pyogenes. Through systematic genomic analyses of 501 disseminated SDSE strains, we demonstrate extensive overlap between the genomes of SDSE and S. pyogenes. More than 75% of core genes are shared between the two species with one third demonstrating evidence of cross-species recombination. Twenty-five percent of mobile genetic element (MGE) clusters and 16 of 55 SDSE MGE insertion regions were shared across species. Assessing potential cross-protection from leading S. pyogenes vaccine candidates on SDSE, 12/34 preclinical vaccine antigen genes were shown to be present in >99% of isolates of both species. Relevant to possible vaccine evasion, six vaccine candidate genes demonstrated evidence of inter-species recombination. These findings demonstrate previously unappreciated levels of genomic overlap between these closely related pathogens with implications for streptococcal pathobiology, disease surveillance and prevention.


Asunto(s)
Infecciones Estreptocócicas , Streptococcus , Vacunas , Humanos , Streptococcus pyogenes/genética , Flujo Génico
13.
Mult Scler J Exp Transl Clin ; 10(1): 20552173241231678, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38410681

RESUMEN

Background: Between 29% and 67% of neuromyelitis optica spectrum disorder patients have cognitive alterations. Objective: To assess the frequency of cognitive impairment in patients with neuromyelitis optica spectrum disorder in Mexico using the Brief International Cognitive Assessment for Multiple Sclerosis. Methods: We evaluated 40 neuromyelitis optica spectrum disorder patients and 40 healthy controls from Mexico. Results: 28 (70.0%) patients with neuromyelitis optica spectrum disorder had cognitive impairment in two or more cognitive domains. Student´s T test showed statistically poor performance by neuromyelitis optica spectrum disorder patients compared to healthy controls on all three neuropsychological test scores. This significant difference was observed on the Symbols Digit Modalities Test (t = 8.875; p ≤ 0.001); California Verbal Learning Test-II memory (t = 10.418; p ≤ 0.001); and Brief Visuospatial Memory Test Revised (t = 6.123; p ≤ 0.001). Conclusions: This study showed that 70% of neuromyelitis optica spectrum disorder patients exhibited cognitive impairment in two or more cognitive domains. Determining the frequency of cognitive impairment will guide the decision of Neuropsychologists in planning cognitive rehabilitation across various domains.

14.
Biomedicines ; 12(2)2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38397883

RESUMEN

A poorly studied issue in women with breast cancer is the role of incretins (GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1)) in the quantity and quality of muscle mass in lean and obese individuals. The current report aims to analyze the patterns of association and the role of incretin in muscle functionality and body composition in women with cancer compared with healthy women (mammography BI-RADS I or II) to elucidate whether GIP and GLP-1 can be used to estimate the risk, in conjunction with overweight or obesity, for breast cancer. We designed a case-control study in women with a breast cancer diagnosis confirmed by biopsy in different clinical stages (CS; n = 87) and healthy women with a mastography BI-RADS I or II within the last year (n = 69). The women were grouped according to body mass index (BMI): lean (<25 kg/m2BS), overweight (≥25-<30 kg/m2BS), and obese (≥30 kg/m2BS). We found that GLP-1 and GIP levels over 18 pg/mL were associated with a risk of breast cancer (GIP OR = 36.5 and GLP-1 OR = 4.16, for the entire sample), particularly in obese women (GIP OR = 8.8 and GLP-1 OR = 6.5), and coincidentally with low muscle quality indexes, showed an association between obesity, cancer, incretin defects, and loss of muscle functionality.

15.
Mult Scler Relat Disord ; 83: 105451, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38245997

RESUMEN

BACKGROUND: Cognitive impairment is observed in 43-70 % of Multiple sclerosis (MS) patients. One of the most widely used batteries for cognitive assessment in this population is the Brief International Cognitive Assessment for MS (BICAMS). The objective of this study was to validate and assess the reliability of the BICAMS in a Mexican population with MS and to obtain and provide regression-based norms. METHODS: One hundred healthy controls (HCs) and 100 patients with multiple sclerosis participated in the present study, and groups were matched for age, years of education and sex. Subjects completed all three tests of the BICAMS. Test-retest measures were obtained from 30 patients to test reliability. RESULTS: The sample´s average age was 43.39 ± 6.03 years old, and the average years of education was 12.55 ± 2.52 years. Approximately 63 % of the participants were female. The groups did not differ in age, years of education, or sex. The MS group performed significantly worse than the HCs group on all three neuropsychological tests. A significant difference was observed for the SDMT (t = 10.166; p=<0.001), CVLT-II (t = 10.949; p=<0.001), and BVMT-R (t = 2.636; p = 0.009). For all comparisons, the effect size (d) for each test was calculated as follows: SDMT= 0.58 and CVLT-II= 0.61. The test-retest coefficients for each test were as follows: SDMT: r = 0.95; CVLT-II: r = 0.84; and BVMT-R = 0.81. CONCLUSION: The BICAMS can provide information on cognitive impairment in MS patients, and this information can be used by neuropsychologists for cognitive rehabilitation in different domains.


Asunto(s)
Disfunción Cognitiva , Esclerosis Múltiple , Humanos , Femenino , Adulto , Persona de Mediana Edad , Masculino , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/psicología , Reproducibilidad de los Resultados , México , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Pruebas Neuropsicológicas , Cognición
16.
Mult Scler Relat Disord ; 82: 105373, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38154347

RESUMEN

BACKGROUND: The modulation of the activity disease in patients with Multiple Sclerosis (MS) that occurs during pregnancy is a helpful model which could provide insight into central disease mechanisms and facilitate treatment. Therefore, the aim of the study was to identify differentially expressed genes in-silico to perform biological function pathway enrichment analysis and protein-protein interaction from pregnant women with MS. METHODS: Transcriptome data were obtained from the Gene Expression Omnibus (GEO) database. We selected the microarray dataset GSE17449. The gene expression dataset contains the data of mononuclear cells from four different groups sought, including seven healthy women (H), four healthy pregnant women (HP), eight women with multiple sclerosis (WMS), and nine women nine months pregnant with multiple sclerosis (PMS). The GSEA software was employed for enrichment analysis, and the REACTOME database was used for biological pathways. The protein-protein interaction (PPI) network was plotted with STRING. The databases used to identify the connection of DEGs with different signaling pathways were KEGG and WIKIPATHWAYS. RESULTS: We identified 42 differentially expressed genes in pregnant women with MS. The significant pathways included IL-10 signaling pathway, ErbB2 activates, the hemoglobin complex (HBD, HBB, HBA1, AHSP, and HBA2), IL-17 signaling pathway (LCN2 and MMP9), antigen processing and presentation, and Th17 cell differentiation (HLA-DQA1), Rap1 signaling pathway (ID1), NOD-Like receptor signaling pathway (CAMP and DEFA4), PD-L1 Signaling, Interferon gamma signaling (MMP9 and ARG1), Neutrophil degranulation (CAMP, DEFA4, ELANE, CEACAM8, S100P, CHI3L1, AZU1, OLFM4, CRISP3, LTF, ARG1, PGLYRP1, and TCN1). In the WIKIPATHWAYS set, significance was found Vitamin B12 metabolism (TCN1, HBB, and HBA2), and IL-18 signaling pathway (S100P). CONCLUSION: This study can be used to understand several essential target genes and pathways identified in the present study, which may serve as feasible targets for MS therapies.


Asunto(s)
Metaloproteinasa 9 de la Matriz , Esclerosis Múltiple , Embarazo , Humanos , Femenino , Esclerosis Múltiple/genética , Transcriptoma , Mapas de Interacción de Proteínas , Biología Computacional , Proteínas Sanguíneas , Chaperonas Moleculares
17.
Antiviral Res ; 222: 105783, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38145755

RESUMEN

The human respiratory syncytial virus (hRSV) is the leading etiologic agent causing respiratory infections in infants, children, older adults, and patients with comorbidities. Sixty-seven years have passed since the discovery of hRSV, and only a few successful mitigation or treatment tools have been developed against this virus. One of these is immunotherapy with monoclonal antibodies against structural proteins of the virus, such as Palivizumab, the first prophylactic approach approved by the Food and Drug Administration (FDA) of the USA. In this article, we discuss different strategies for the prevention and treatment of hRSV infection, focusing on the molecular mechanisms against each target that underly the rational design of antibodies against hRSV. At the same time, we describe the latest results regarding currently approved therapies against hRSV and the challenges associated with developing new candidates.


Asunto(s)
Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Lactante , Niño , Humanos , Anciano , Antivirales/uso terapéutico , Palivizumab/uso terapéutico , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/prevención & control , Anticuerpos Monoclonales/uso terapéutico
18.
Euro Surveill ; 28(36)2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37676143

RESUMEN

Since autumn 2022, observed numbers of paediatric invasive group A Streptococcus infections in Portugal (n = 89) were higher than in pre-COVID-19 seasons. Between September 2022 and May 2023, the dominant diagnoses were pneumonia (25/79), mostly with empyema (20/25), and sepsis (22/79). A number of cases required admission to intensive care (27/79) and surgery (35/79), and the case fatality rate was 5.1% (4/79). Genomic sequencing (n = 55) revealed multiple genetic lineages, dominated by the M1UK sublineage (26/55) and more diverse emm12 isolates (12/55).


Asunto(s)
COVID-19 , Infecciones Estreptocócicas , Humanos , Niño , Portugal/epidemiología , Streptococcus pyogenes/genética , Mapeo Cromosómico , Infecciones Estreptocócicas/diagnóstico , Infecciones Estreptocócicas/epidemiología , Reino Unido
19.
J Clin Med ; 12(13)2023 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-37445568

RESUMEN

Neurotuberculosis (neuroTB) is a devastating disease, and is difficult to diagnose. The aim of this study was to analyze the clinical and imaging characteristics, and outcomes of a retrospective cohort (2000-2022) of hospitalized patients diagnosed with intraspinal and intracranial neuroTB. This work was designed through clinical, laboratory and imaging findings. Variables included: demographic data, history of tuberculosis, neurological complications, comorbidities and outcomes. Morbi-mortality risk factors were identified by univariate analysis. The cohort included: 103 patients with intraspinal and 82 with intracranial neuroTB. During the study period, in-hospital mortality of 3% for intraspinal and 29.6% for intracranial neuroTB was estimated. Motor deficit was found in all patients with intraspinal neuroTB. Risk factors for the unfavorable outcome of patients with intraspinal neuroTB were: age ≥ 40 years, diabetes mellitus (DM), diagnostic delay, kyphosis and spondylodiscitis ≥ 3 levels of involvement. Among the patients with intracranial neuroTB, 79/82 (96.3%) had meningitis and 22 patients had HIV infection (10 of them died). Risk factors for mortality from intracranial neuroTB were: HIV infection, hydrocephalus, stroke, lymphopenia and disseminated and gastrointestinal TB. Patients with intraspinal neuroTB had a significant number of destroyed vertebrae that determined their neurological deficit status. The mortality burden in intracranial neuroTB was conditioned by HIV infection and renal transplantation patients.

20.
Micromachines (Basel) ; 14(7)2023 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-37512590

RESUMEN

The formation of microparticles (MPs) of biocompatible and biodegradable hydrogels such as polyethylene glycol diacrylate (PEGDA) utilizing microfluidic devices is an attractive option for entrapment and encapsulation of active principles and microorganisms. Our research group has presented in previous studies a formulation to produce these hydrogels with adequate physical and mechanical characteristics for their use in the formation of MPs. In this work, hydrogel MPs are formed based on PEGDA using a microfluidic device with a T-junction design, and the MPs become hydrogel through a system of photopolymerization. The diameters of the MPs are evaluated as a function of the hydrodynamic condition flow rates of the continuous (Qc) and disperse (Qd) phases, measured by optical microscopy, and characterized through scanning electron microscopy. As a result, the following behavior is found: the diameter is inversely proportional to the increase in flow in the continuous phase (Qc), and it has a significant statistical effect that is greater than that in the flow of the disperse phase (Qd). While the diameter of the MPs is proportional to Qd, it does not have a significant statistical effect on the intervals of flow studied. Additionally, the MPs' polydispersity index (PDI) was measured for each experimental hydrodynamic condition, and all values were smaller than 0.05, indicating high homogeneity in the MPs. The microparticles have the potential to entrap pharmaceuticals and microorganisms, with possible pharmacological and bioremediation applications.

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