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Lyme disease is the most common vector-borne disease in North America and Europe. The clinical manifestations of Lyme disease vary based on the genospecies of the infecting Borrelia burgdorferi spirochete, but the microbial genetic elements underlying these associations are not known. Here, we report the whole genome sequence (WGS) and analysis of 299 B. burgdorferi (Bb) isolates derived from patients in the Eastern and Midwestern US and Central Europe. We develop a WGS-based classification of Bb isolates, confirm and extend the findings of previous single- and multi-locus typing systems, define the plasmid profiles of human-infectious Bb isolates, annotate the core and strain-variable surface lipoproteome, and identify loci associated with disseminated infection. A core genome consisting of ~900 open reading frames and a core set of plasmids consisting of lp17, lp25, lp36, lp28-3, lp28-4, lp54, and cp26 are found in nearly all isolates. Strain-variable (accessory) plasmids and genes correlate strongly with phylogeny. Using genetic association study methods, we identify an accessory genome signature associated with dissemination in humans and define the individual plasmids and genes that make up this signature. Strains within the RST1/WGS A subgroup, particularly a subset marked by the OspC type A genotype, have increased rates of dissemination in humans. OspC type A strains possess a unique set of strongly linked genetic elements including the presence of lp56 and lp28-1 plasmids and a cluster of genes that may contribute to their enhanced virulence compared to other genotypes. These features of OspC type A strains reflect a broader paradigm across Bb isolates, in which near-clonal genotypes are defined by strain-specific clusters of linked genetic elements, particularly those encoding surface-exposed lipoproteins. These clusters of genes are maintained by strain-specific patterns of plasmid occupancy and are associated with the probability of invasive infection.
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Borrelia burgdorferi , Doença de Lyme , Humanos , Borrelia burgdorferi/genética , Genótipo , Sequenciamento Completo do Genoma , Plasmídeos/genéticaRESUMO
Retinoblastoma protein is central in signaling networks of fundamental cell decisions such as proliferation and differentiation in all metazoans and cancer development. Immunostaining and biochemical evidence demonstrated that during interphase retinoblastoma protein is in the nucleus and is hypophosphorylated, and during mitosis is in the cytoplasm and is hyperphosphorylated. The purpose of this study was to visualize in vivo in a non-diseased tissue, the dynamic spatial and temporal nuclear exit toward the cytoplasm of this protein during mitosis and its return to the nucleus to obtain insights into its potential cytosolic functions. Using high-resolution time-lapse images from confocal microscopy, we tracked in vivo the ortholog in plants the RETINOBLASTOMA RELATED (RBR) protein tagged with Green Fluorescent Protein (GFP) in Arabidopsis thaliana's root. RBR protein exits from dense aggregates in the nucleus before chromosomes are in prophase in less than 2 min, spreading outwards as smaller particles projected throughout the cytosol during mitosis like a diffusive yet controlled event until telophase, when the daughter's nuclei form; RBR returns to the nuclei in coordination with decondensing chromosomal DNA forming new aggregates again in punctuated larger structures in each corresponding nuclei. We propose RBR diffused particles in the cytoplasm may function as a cytosolic sensor of incoming signals, thus coordinating re-aggregation with DNA is a mechanism by which any new incoming signals encountered by RBR may lead to a reconfiguration of the nuclear transcriptomic context. The small RBR diffused particles in the cytoplasm may preserve topologic-like properties allowing them to aggregate and restore their nuclear location, they may also be part of transient cytoplasmic storage of the cellular pre-mitotic transcriptional context, that once inside the nuclei may execute both the pre mitosis transcriptional context as well as new transcriptional instructions.
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BACKGROUND: Postinfectious Lyme arthritis (LA) is associated with dysregulated immunity and autoreactive T- and B-cell responses in joints. Here we explored the role of host genetic variation in this outcome. METHODS: The frequency of 253 702 single-nucleotide polymorphisms (SNPs) was determined in 147 patients with LA (87 with postinfectious LA and 60 with antibiotic-responsive LA), and for comparison in 90 patients with erythema migrans or the general population (n = 2504). Functional outcome of candidate SNPs was assessed by evaluating their impact on clinical outcome and on immune responses in blood and synovial fluid in patients with LA. RESULTS: Six SNPs associated with late cornified envelope (LCE3) genes were present at greater frequency in patients with postinfectious LA compared to those with antibiotic-responsive LA (70% vs 30%; odds ratio, 2; P < .01). These SNPs were associated with heightened levels of inflammatory Th17 cytokines in serum but lower levels of interleukin 27, a regulatory cytokine, implying that they may contribute to dysregulated Th17 immunity in blood. Moreover, in patients with postinfectious LA, the levels of these Th17 mediators correlated directly with autoantibody responses in synovial fluid, providing a possible link between LCE3 SNPs, maladaptive systemic Th17 immunity, and autoreactive responses in joints. CONCLUSIONS: Variation in the LCE3 locus, a known genetic risk factor in psoriasis and psoriatic arthritis, is associated with dysregulated systemic Th17 immunity and heightened autoantibody responses in joints. These findings underscore the importance of host genetic predisposition and systemic Th17 immunity in the pathogenesis of postinfectious (antibiotic-refractory) Lyme arthritis.
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Doença de Lyme , Polimorfismo de Nucleotídeo Único , Células Th17 , Humanos , Doença de Lyme/genética , Doença de Lyme/imunologia , Células Th17/imunologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Líquido Sinovial/imunologia , Idoso , Citocinas/genética , Citocinas/metabolismo , Artrite Infecciosa/genética , Artrite Infecciosa/imunologia , Adulto JovemRESUMO
INTRODUCTION: Temporal Lobe Epilepsy (TLE) has been associated with memory impairments, which are typically linked to hippocampal and mesial temporal cortex lesions. Considering the presence of extensive bidirectional frontotemporal connections, it can be hypothesized that executive dysfunction in TLE is modulated by the lateralization of the epileptic foci. MATERIAL AND METHODS: A comprehensive neuropsychological executive functions protocol was administered to 63 participants, including 42 individuals with temporal lobe epilepsy (20 with right-TLE and 22 with left-TLE) and 21 healthy controls aged 20-49. RESULTS: The results indicate that TLE patients exhibit poorer executive performance compared to healthy controls in working memory (F(2,60) = 4.18, p <.01), planning (F(2,60) = 4.71, p <.05), set shifting (F(2,60) = 10.1, p <.001), phonetic verbal fluency (F(2,60) = 11.71, p <.01) and semantic verbal fluency (F(2,60) = 9.61, p <.001. No significant differences were found in cognitive inhibition. Furthermore, right-TLE patients showed lower performance than left-TLE in set shifting (F(1,61) = 6.45, p <.05), while no significant differences were observed in working memory, planning, inhibition, and verbal fluency. CONCLUSIONS: This research emphasize the importance of considering the lateralization of the temporal lobe focus to achieve a more accurate neuropsychological characterization. The cognitive differences between left and right TLE patients highlight the need for individualized approaches in their treatment and care.
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Epilepsia do Lobo Temporal , Epilepsia , Humanos , Função Executiva/fisiologia , Testes Neuropsicológicos , Lobo Temporal , Cognição/fisiologiaRESUMO
BACKGROUND: Hospitalizations for ambulatory care sensitive conditions (ACSC) incur substantial costs on the health system that could be partially avoided with adequate outpatient care. Complications of chronic diseases, such as diabetes mellitus (DM), are considered ACSC. Previous studies have shown that hospitalizations due to diabetes have a significant financial burden. In Mexico, DM is a major health concern and a leading cause of death, but there is limited evidence available. This study aimed to estimate the direct costs of hospitalizations by DM-related ACSC in the Mexican public health system. METHODS: We selected three hospitals from each of Mexico's main public institutions: the Mexican Social Security Institute (IMSS), the Ministry of Health (MoH), and the Institute of Social Security and Services for State Workers (ISSSTE). We employed a bottom-up microcosting approach from the healthcare provider perspective to estimate the total direct costs of hospitalizations for DM-related ACSC. Input data regarding length of stay (LoS), consultations, medications, colloid/crystalloid solutions, procedures, and laboratory/medical imaging studies were obtained from clinical records of a random sample of 532 hospitalizations out of a total of 1,803 DM-related ACSC (ICD-10 codes) discharges during 2016. RESULTS: The average cost per DM-related ACSC hospitalization varies among institutions, ranging from $1,427 in the MoH to $1,677 in the IMSS and $1,754 in the ISSSTE. The three institutions' largest expenses are LoS and procedures. Peripheral circulatory and renal complications were the major drivers of hospitalization costs for patients with DM-related ACSC. Direct costs due to hospitalizations for DM-related ACSC in these three institutions represent 1% of the gross domestic product (GDP) dedicated to health and social services and 2% of total hospital care expenses. CONCLUSIONS: The direct costs of hospitalizations for DM-related ACSC vary considerably across institutions. Disparities in such costs for the same ACSC among different institutions suggest potential disparities in care quality across primary and hospital settings (processes and resource utilization), which should be further investigated to ensure optimal supply utilization. Prioritizing preventive measures for peripheral circulatory and renal complications in DM patients could be highly beneficial.
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Assistência Ambulatorial , Diabetes Mellitus , Hospitalização , Humanos , México , Diabetes Mellitus/terapia , Diabetes Mellitus/economia , Assistência Ambulatorial/economia , Masculino , Feminino , Pessoa de Meia-Idade , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Adulto , Custos Hospitalares/estatística & dados numéricos , Idoso , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Adolescente , Adulto JovemRESUMO
Gastric cancer (GC) remains a significant global health challenge, with high mortality rates, especially in developing countries. Current treatments are invasive and have considerable risks, necessitating the exploration of safer alternatives. Quercetin (QRC), a flavonoid present in various plants and foods, has demonstrated multiple health benefits, including anticancer properties. This study investigated the therapeutic potential of QRC in the treatment of GC. We utilized advanced molecular techniques to assess the impact of QRC on GC cells, examining its effects on cellular pathways and gene expression. Our findings indicate that QRC significantly inhibits GC cell proliferation and induces apoptosis, suggesting its potential as a safer therapeutic option for GC treatment. Further research is required to validate these results and explore the clinical applications of QRC in cancer therapy.
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Apoptose , Proliferação de Células , Biologia Computacional , Quercetina , Neoplasias Gástricas , Quercetina/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Humanos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacosRESUMO
Invasive fungal disease accounts for about 3.8â million deaths annually, an unacceptable rate that urgently prompts the discovery of new knowledge-driven treatments. We report the use of camelid single-domain nanobodies (Nbs) against fungal ß-1,3-glucanosyltransferases (Gel) involved in ß-1,3-glucan transglycosylation. Crystal structures of two Nbs with Gel4 from Aspergillus fumigatus revealed binding to a dissimilar CBM43 domain and a highly conserved catalytic domain across fungal species, respectively. Anti-Gel4 active site Nb3 showed significant antifungal efficacy in vitro and in vivo prophylactically and therapeutically against different A. fumigatus and Cryptococcus neoformans isolates, reducing the fungal burden and disease severity, thus significantly improving immunocompromised animal survival. Notably, C. deneoformans (serotypeâ D) strains were more susceptible to Nb3 and genetic Gel deletion than C. neoformans (serotype A) strains, indicating a key role for ß-1,3-glucan remodelling in C. deneoformans survival. These findings add new insight about the role of ß-1,3-glucan in fungal biology and demonstrate the potential of nanobodies in targeting fungal enzymes to combat invasive fungal diseases.
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Aspergillus fumigatus , Domínio Catalítico , Anticorpos de Domínio Único , Anticorpos de Domínio Único/química , Anticorpos de Domínio Único/imunologia , Anticorpos de Domínio Único/farmacologia , Aspergillus fumigatus/imunologia , Aspergillus fumigatus/enzimologia , Cryptococcus neoformans/enzimologia , Cryptococcus neoformans/imunologia , Antifúngicos/química , Antifúngicos/farmacologia , Animais , Camundongos , Glucana Endo-1,3-beta-D-GlucosidaseRESUMO
Patients who have Lyme neuroborreliosis (LNB) might experience lingering symptoms that persist despite antibiotic drug therapy. We tested whether those symptoms are caused by maladaptive immune responses by measuring 20 immune mediators in serum and cerebrospinal fluid (CSF) in 79 LNB patients followed for 1 year. At study entry, most mediators were highly concentrated in CSF, the site of the infection. Those responses resolved with antibiotic therapy, and associations between CSF cytokines and signs and symptoms of LNB were no longer observed. In contrast, subjective symptoms that persisted after use of antibiotics were associated with increased levels of serum interferon-α (IFN-α), which were already observed at study entry, and remained increased at each subsequent timepoint. Highest IFN-α levels corresponded with severe disease. Although the infection serves as the initial trigger, sequelae after antibiotic therapy are associated with unremitting systemic IFN-α levels, consistent with the pathogenic role of this cytokine in interferonopathies in other conditions.
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Neuroborreliose de Lyme , Humanos , Neuroborreliose de Lyme/tratamento farmacológico , Neuroborreliose de Lyme/diagnóstico , Interferon-alfa/uso terapêutico , Citocinas , Fatores Imunológicos , Antibacterianos/uso terapêuticoRESUMO
BACKGROUND: Sahaja Yoga Meditation draws on many religious traditions and uses a variety of techniques including Christian prayer to reach a state known as thoughtless awareness, or mental silence. While there are many studies on the neural correlates of meditation, few studies have focused on the neural correlates of praying. Thus, the aim of our research was to study the neural activity associated with the prayer practices in Sahaja Yoga Mediation, which have not been studied before, to explore effects beyond repetitive speech or "mantra effects". Sixteen experienced Sahaja Yoga Meditation practitioners were scanned using task based functional Magnetic Resonance Imaging while performing formalised and improvised forms of praying and their equivalent secular tasks. RESULTS: Our results showed the deactivation of bilateral thalamus during both prayers compared to secular conditions and the activation in the medial prefrontal cortex that was reduced by religious and formalised secular speech conditions but increased during improvised secular speech; similarly, frontal regions were deactivated when comparing prayers to their secular equivalents. DISCUSSION: These results seem to depict two important factors related with praying in Sahaja Yoga Meditation merging inner concentration and social cognition. First, the perception of the surroundings mediated by the thalamus may be decreased during these prayers probably due to the establishment of inner concentration and, second, frontal deactivation effects could be related to reduced social judgement and 'mentalizing', particularly in the medial prefrontal cortex. Our findings suggest that praying by Sahaja Yoga Meditation practitioners is neurophenomenologically different from the social cognitive attempt of praying within Christian praying practices.
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Meditação , Yoga , Humanos , Yoga/psicologia , Meditação/psicologiaRESUMO
PURPOSE: To evaluate whether intraoperative neuromonitoring (IONM), including pre-embolization lidocaine injection challenge ("provocative testing") is associated with reduced risk of irreversible nerve injury during embolization of peripheral arteriovenous malformations (AVMs). MATERIALS AND METHODS: Medical records of patients with peripheral AVMs who underwent embolotherapy with IONM with provocative testing between 2012 and 2021 were reviewed retrospectively. Data collected included patient demographic characteristics, AVM location and size, embolic agent used, IONM signal changes after lidocaine and embolic agent injections, postprocedural adverse events, and clinical outcomes. Decisions regarding whether embolization would proceed at specific locations were based on IONM findings after the lidocaine challenge and as embolization proceeded. RESULTS: A cohort of 17 patients (mean age, 27 years ± 19; 5 women) who underwent 59 image-guided embolization procedures with adequate IONM data was identified. No permanent neurologic deficits occurred. Transient neurologic deficits were observed in 3 patients (4 sessions), comprising skin numbness (2 patients), extremity weakness (1 patient), and extremity weakness and numbness (1 patient). All neurologic deficits resolved by postoperative day 4 without additional treatment. CONCLUSIONS: IONM, including provocative testing, during AVM embolization may minimize potential nerve injury.
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Embolização Terapêutica , Malformações Arteriovenosas Intracranianas , Humanos , Feminino , Adulto , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/terapia , Malformações Arteriovenosas Intracranianas/etiologia , Hipestesia/etiologia , Hipestesia/terapia , Estudos Retrospectivos , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/métodos , Injeções , Resultado do TratamentoRESUMO
In order to use classical molecular dynamics to complement experiments accurately, it is important to use robust descriptions of the system. The interactions between biomolecules, like aspartic and glutamic acid, and dissolved ions are often studied using standard biomolecular force-fields, where the interactions between biomolecules and cations are often not parameterized explicitly. In this study, we have employed metadynamics simulations to investigate different interactions of Ca with aspartic and glutamic acid and constructed the free energy profiles of Ca2+-carboxylate association. Starting from a generally accepted, AMBER-based force field, the association was substantially over and under-estimated, depending on the choice of water model (TIP3P and SPC/fw, respectively). To rectify this discrepancy, we have replaced the default calcium parameters. Additionally, we modified the σij value in the hetero-atomic Lennard-Jones interaction by 0.5% to further improve the interaction between Ca and carboxylate, based on comparison with the experimentally determined association constant for Ca with the carboxylate group of L-aspartic acid. The corrected description retrieved the structural properties of the ion pair in agreement with the original biomolecule - Ca2+ interaction in AMBER, whilst also producing an association constant comparable to experimental observations. This refined force field was then used to investigate the interactions between amino acids, calcium and carbonate ions during biogenic and biomimetic calcium carbonate mineralisation.
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Aminoácidos , Simulação de Dinâmica Molecular , Aminoácidos/química , Cálcio/química , Ácido Glutâmico , Cátions , Água/química , Ácidos CarboxílicosRESUMO
Developing ambulatory health services (AHS) of optimal quality is a pending issue for many health systems at a global level, especially in middle- and low-income countries. An effective health response requires indicators to measure the quality of care that are context-specific and feasible for routine monitoring. This paper aimed to design and validate indicators for assessing the technical and interpersonal quality dimensions for type 2 diabetes (T2D) and acute respiratory infections (ARI) care in AHS. The study was conducted in two stages. First, technical and user-centered-based indicators of quality of care for T2D and ARI care were designed following international recommendations, mainly from the American Diabetes Association standards and the National Institute for Health and Care Excellence guidelines. We then assessed the validity, reliability, relevance, and feasibility of the proposed indicators implementing the modified Delphi technique. A panel of 17 medical experts from five countries scored the indicators using two electronic questionnaires, one for each reason for consultation selected, sent by email in two sequential rounds of rating. We defined the levels of consensus according to the overall median for each performance category, which was established as the threshold. Selected indicators included those with scores equal to or higher than the threshold. We designed 36 T2D indicators, of which 16 were validated for measuring the detection of risks and complications, glycemic control, pharmacological treatment, and patient-centered care. Out of the 22 indicators designed for ARI, we validated 10 for diagnosis, appropriate prescription of antimicrobials, and patient-centered care. The validated indicators showed consistency for the dimensions analyzed. Hence, they proved to be a potentially reliable and valuable tool for monitoring the performance of the various T2D and ARI care processes in AHS. Further research will be needed to verify the applicability of the validated indicators in routine clinical practice.
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Diabetes Mellitus Tipo 2 , Infecções Respiratórias , Humanos , Diabetes Mellitus Tipo 2/terapia , Reprodutibilidade dos Testes , Infecções Respiratórias/terapia , Consenso , Serviços de SaúdeRESUMO
The dolphinfish (Coryphaena hippurus) is a globally distributed marine predator that supports one of the most important coastal fisheries along the Eastern Tropical Pacific (ETP), but its spatial movements in this area are poorly understood. Stable isotope values (δ13 C and δ15 N) of white muscle from dolphinfish (n = 220) captured at different locations across the ETP (i.e., Mexico, Costa Rica, Ecuador, Peru and oceanic areas) were normalized to copepod baseline stable isotope values to estimate dolphinfish trophic position, movements and population dispersal. Movement or residence patterns were inferred from the difference in δ15 N values (Δ15 Ndolphinfish-copepod ) between copepods and dolphinfish muscle. Baseline corrected isotope values (δ13 Cdolphinfish-copepod and δ15 Ndolphinfish-copepod ) of dolphinfish muscle were used to estimate isotopic niche metrics and infer population dispersal across isoscapes. Values of δ13 C and δ15 N differed between juvenile and adult dolphinfish and across the ETP. Trophic position estimates ranged from 3.1 to 6.0 with a mean of 4.6. Adults and juveniles had similar trophic position estimates, whereas isotopic niche areas (SEA 2 ) of adults were greater relative to juveniles in every location. Adult dolphinfish showed "moderate movement by some individuals" in all locations based on Δ15 Ndolphinfish-copepod values, except for Costa Rica where adults were classified with "high degree of movement by some individuals" whereas juveniles showed "limited movement" in all areas except Mexico. Population dispersal based on Δ15 Ndolphinfish-copepod values showed "moderate" and "high" dispersal for adults and "no dispersal" for most juveniles, except for Mexico. This study provides insight into potential dolphinfish spatial mobility across an area of interest for multiple nations, which can help to improve stock assessments and management of the species.
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Copépodes , Perciformes , Animais , Carbono , Isótopos de Nitrogênio , Músculos , Pesqueiros , Isótopos de CarbonoRESUMO
Invasive fungal infections represent a global health threat. They are associated with high mortality and morbidity rates, partly due to the ineffectiveness of the available antifungal agents. The rampant increase in infections recalcitrant to the current antifungals has worsened this scenario and made the discovery of new and more effective antifungals a pressing health issue. In this study, 65 extracts from marine organisms of the Yucatan Peninsula, Mexico, were screened for antifungal activity against Candida albicans and Candida glabrata, two of the most prevalent fungal species that cause nosocomial invasive fungal infections worldwide. A total of 51 sponges, 13 ascidians and 1 gorgonian were collected from the coral reef and mangrove forest in the Yucatan Peninsula (Mexico) and extracted with organic solvents. Nine crude extracts showed potent antifungal activity, of which four extracts from the sponge species Aiolochroia crassa, Amphimedon compressa, Monanchora arbuscula and Agelas citrina had promising activity against Candida spp. Bioassay-guided fractionation of the M. arbuscula extract revealed the remarkable fungicidal activity of some fractions. Analysis of the chemical composition of one of the most active fractions by UHPLC-HRMS and NMR indicated the presence of mirabilin B and penaresidin B, and their contribution to the observed antifungal activity is discussed. Overall, this work highlights marine organisms of the Yucatan Peninsula as important reservoirs of natural products with promising fungicidal activity, which may greatly advance the treatment of invasive fungal infections, especially those afflicting immunosuppressed patients.
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Antifúngicos , Infecções Fúngicas Invasivas , Antifúngicos/química , Candida , México , Organismos Aquáticos , Testes de Sensibilidade Microbiana , Infecções Fúngicas Invasivas/tratamento farmacológicoRESUMO
Lyme neuroborreliosis (LNB) in Europe may manifest with painful meningoradiculoneuritis (also known as Bannwarth syndrome) or lymphocytic meningitis with or without cranial neuritis (peripheral facial palsy). We assessed host immune responses and the prevalence of TLR1 (toll-like receptor 1)-1805GG polymorphism to gain insights into the pathophysiology of these conditions. Regardless of LNB manifestation, most mediators associated with innate and adaptive immune responses were concentrated in cerebrospinal fluid; serum levels were unremarkable. When stratified by specific clinical manifestation, patients with meningoradiculoneuritis had higher levels of B-cell chemoattractants CXC motif chemokine ligand (CXCL) 12 and CXCL13 and T-cell-associated mediators CXCL9, CXCL10, and interleukin 17, compared with those without radicular pain. Moreover, these patients had a higher frequency of TLR1-1805GG polymorphism and more constitutional symptoms. These findings demonstrate that meningoradiculoneuritis is a distinct clinical entity with unique immune and genetic pathophysiology, providing new considerations for the study of LNB and borrelial meningoradiculitis.
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Borrelia , Citocinas , Paralisia Facial , Neuroborreliose de Lyme , Quimiocinas/metabolismo , Citocinas/metabolismo , Europa (Continente) , Humanos , Neuroborreliose de Lyme/líquido cefalorraquidiano , Neuroborreliose de Lyme/diagnóstico , Neuroborreliose de Lyme/genética , PrevalênciaRESUMO
Three new diterpene alkaloids, (+)-8-epiagelasine T (1), (+)-10-epiagelasine B (2), and (+)-12-hydroxyagelasidine C (3), along with three known compounds, (+)-ent-agelasine F (4), (+)-agelasine B (5), and (+)-agelasidine C (6), were isolated from the sponge Agelas citrina, collected on the coasts of the Yucatán Peninsula (Mexico). Their chemical structures were elucidated by 1D and 2D NMR spectroscopy, HRESIMS techniques, and a comparison with literature data. Although the synthesis of (+)-ent-agelasine F (4) has been previously reported, this is the first time that it was isolated as a natural product. The evaluation of the antimicrobial activity against the Gram-positive pathogens Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis showed that all of them were active, with (+)-10-epiagelasine B (2) being the most active compound with an MIC in the range of 1-8 µg/mL. On the other hand, the Gram-negative pathogenes Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae were also evaluated, and only (+)-agelasine B (5) showed a moderate antibacterial activity with a MIC value of 16 µg/mL.
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Agelas , Anti-Infecciosos , Agelas/química , Animais , Antibacterianos/química , Anti-Infecciosos/química , Alcaloides Diterpenos , México , Testes de Sensibilidade Microbiana , Estrutura MolecularRESUMO
OBJETIVO: Comparar la calidad de atención a neonatos con sepsis neonatal, hipoxia intrauterina, prematuridad y asfixia perinatal en hospitales acreditados (HA) y no acreditados (HNA). Material y métodos. Se evaluaron 28 hospi-tales de la Secretaría de Salud en 11 estados de México; la evaluación incluyó infraestructura, equipamiento e insumos, procesos de gestión de calidad e indicadores de calidad clínica. Se utilizó LQAS y se estimó el cumplimiento promedio de criterios e indicadores en HA y HNA. RESULTADOS: Hubo diferencias significativas en favor de HA en equipamiento e insumos y no significativas en existencia y funcionamiento de los comités hospitalarios. No hubo diferencias consistentes ni significativas en cumplimiento de indicadores clínicos entre los HA y HNA. CONCLUSIONES: La acreditación para la atención de neonatos con los diagnósticos seleccionados no se asocia a diferencias en la calidad de la atención.
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Acreditação , Hospitais , Feminino , Humanos , Recém-Nascido , México/epidemiologia , Gravidez , Qualidade da Assistência à Saúde , Estudos RetrospectivosRESUMO
Epilepsy is a disease that decreases the quality of life of patients; it is also among the most common neurological diseases. Several studies have approached the classification and prediction of seizures by using electroencephalographic data and machine learning techniques. A large diversity of features has been extracted from electroencephalograms to perform classification tasks; therefore, it is important to use feature selection methods to select those that leverage pattern recognition. In this study, the performance of a set of feature selection methods was compared across different classification models; the classification task consisted of the detection of ictal activity from the CHB-MIT and Siena Scalp EEG databases. The comparison was implemented for different feature sets and the number of features. Furthermore, the similarity between selected feature subsets across classification models was evaluated. The best F1-score (0.90) was reported by the K-nearest neighbor along with the CHB-MIT dataset. Results showed that none of the feature selection methods clearly outperformed the rest of the methods, as the performance was notably affected by the classifier, dataset, and feature set. Two of the combinations (classifier/feature selection method) reporting the best results were K-nearest neighbor/support vector machine and random forest/embedded random forest.
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Epilepsia , Qualidade de Vida , Algoritmos , Eletroencefalografia/métodos , Epilepsia/diagnóstico , Humanos , Convulsões/diagnóstico , Processamento de Sinais Assistido por Computador , Máquina de Vetores de SuporteRESUMO
The effect of different high-pressure processing (HPP) treatments on casein micelles was analyzed through scanning electron microscopy (SEM) and a particle size distribution analysis. Raw whole and skim milk samples were subjected to HPP treatments at 400, 500 and 600 MPa for Come-Up Times (CUT) up to 15 min at ambient temperature. Three different phenomena were observed in the casein micelles: fragmentation, alterations to shape and agglomeration. The particle size distribution analysis determined that, as pressure and time treatment increased, the three phenomena intensified. First, the size of the casein micelles began to decrease as their fragmentation occurred. Subsequently, the casein micelles lost roundness, and their shape deformed. Finally, in the most intense treatments (higher pressures and/or longer times), the micelles fragments began to agglomerate, which resulted in an increase in their average diameter. Homogenization and defatting had no significant effect on the casein micelles; however, the presence of fat in whole milk samples was bioprotective, as the effects of the three phenomena appeared faster in treated skim milk samples. Through this study, it was concluded that the size and structure of casein micelles are greatly altered during high-pressure treatment. These results provide information that broadens the understanding of the changes induced on casein micelles by high-pressure treatments at room temperature.
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Caseínas , Micelas , Animais , Caseínas/química , Leite/química , Proteínas do Leite/químicaRESUMO
The tropical endogeic earthworm Pontoscolex corethrurus, a non-standard species used in ecotoxicity, has been found in crude oil-contaminated habitats. We estimated the removal of total hydrocarbons from heavy crude "Maya" oil on an artificially contaminated soil with a median lethal concentration of P. corethrurus and an addition of oil palm bagasse. P. corethrurus had a high survival rate, and the addition of oil palm bagasse led to a greater growth and an increase in abundance of bacteria and fungi. The activity of P. corethrurus and the nutritional quality of oil palm bagasse had a significant impact on the removal of a larger amount of petroleum hydrocarbons from contaminated soil. We concluded that the endogeic earthworm P. corethrurus and oil palm bagasse acted synergistically to achieve a more effective removal of total petroleum hydrocarbons from soil. These results show the potential for using P. corethrurus to remove, either directly or indirectly, crude oil from soil.