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The 2024 Interamerican Society of Cardiology (SIAC) guidelines on cardiorespiratory rehabilitation (CRR) in pediatric patients with congenital heart disease aim to gather and evaluate all relevant evidence available on the topic to unify criteria and promote the implementation of CRR programs in this population in Latin America and other parts of the world. Currently, there is no unified CRR model for the pediatric population. Consequently, our goal was to create these CRR guidelines adapted to the characteristics of congenital heart disease and the physiology of this population, as well as to the realities of Latin America. These guidelines are designed to serve as a support for health care workers involved in the care of this patient group who wish to implement a CRR program in their workplace. The guidelines include an easily reproducible program model that can be implemented in any center. The members of this Task Force were selected by the SIAC on behalf of health care workers dedicated to the care of pediatric patients with congenital heart disease. To draft the document, the selected experts performed a thorough review of the published evidence.
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Rehabilitación Cardiaca , Cardiopatías Congénitas , Humanos , Cardiopatías Congénitas/rehabilitación , Niño , Rehabilitación Cardiaca/métodos , Cardiología , Sociedades MédicasRESUMEN
Peptidoglycan hydrolases are enzymes responsible for breaking the peptidoglycan present in the bacterial cell wall, facilitating cell growth, cell division and peptidoglycan turnover. Xanthomonas citri subsp. citri (X. citri), the causal agent of citrus canker, encodes an Escherichia coli M23 peptidase EnvC homolog. EnvC is a LytM factor essential for cleaving the septal peptidoglycan, thereby facilitating the separation of daughter cells. In this study, the investigation focused on EnvC contribution to the virulence and cell separation of X. citri. It was observed that disruption of the X. citri envC gene (ΔenvC) led to a reduction in virulence. Upon inoculation into leaves of Rangpur lime (Citrus limonia Osbeck), the X. citri ΔenvC exhibited a delayed onset of citrus canker symptoms compared with the wild-type X. citri. Mutant complementation restored the wild-type phenotype. Sub-cellular localization confirmed that X. citri EnvC is a periplasmic protein. Moreover, the X. citri ΔenvC mutant exhibited elongated cells, indicating a defect in cell division. These findings support the role of EnvC in the regulation of cell wall organization, cell division, and they clarify the role of this peptidase in X. citri virulence.
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BACKGROUND: Studies in human medicine have concluded that acetazolamide reduces pain associated with carbon dioxide insufflation during laparoscopic surgery. However, there are no published reports regarding the use of acetazolamide for this purpose in companion animals, despite the increasing popularity of laparoscopic techniques in veterinary medicine due to their advantages over open surgeries. OBJECTIVES: Thirty mixed-breed female dogs were included in the study and randomly assigned to one of three groups: OVE (median celiotomy ovariectomy; n = 10), OVEL (laparoscopic ovariectomy, n = 10) and OVELA (laparoscopic ovariectomy with acetazolamide preoperative administration; n = 10). Experienced surgeons performed all procedures, and the anaesthetic and analgesic protocols were identical for all animals. Acetazolamide was administered orally (at a dose of 25 mg/kg) 2 h prior to induction in the OVELA group. Postoperative pain was evaluated using serum cortisol, salivary cortisol, and the University of Melbourne Pain Scale (UMPS) Score. RESULTS: Any statistical differences were observed in the UMPS scores when the OVELA group was compared to the OVEL group at 1 h after surgery (p = 0.515), 12 h (p = 0.375) and 24 h (p = 0.242). Animals undergoing open surgery (OVE group) had significantly higher pain scores at all times after surgery when compared with OVEL and OVELA groups. A high positive correlation (r = 0.792; p = 0.01) was found between serum and saliva cortisol concentrations. Mean saliva cortisol concentration was not significantly lower for the OVELA group compared to the other groups. CONCLUSIONS: This study found evidence that preoperative administration of acetazolamide may be beneficial in managing postoperative pain in dogs after laparoscopic surgeries. However, further research with a larger sample size is needed to confirm this and to determine if acetazolamide should be included in a multimodal postoperative analgesia protocol for laparoscopic ovariectomy in dogs.
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Enfermedades de los Perros , Laparoscopía , Animales , Perros , Femenino , Acetazolamida/uso terapéutico , Enfermedades de los Perros/cirugía , Enfermedades de los Perros/tratamiento farmacológico , Hidrocortisona/uso terapéutico , Laparoscopía/veterinaria , Ovariectomía/efectos adversos , Ovariectomía/veterinaria , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/veterinaria , Premedicación/veterinariaRESUMEN
The construction of a data bank concerning metal and metalloid content of bioindicator fish from coastal areas is very important as it can help environmental managers in decision making. In natural conditions, the concentration of elements can be influenced by abiotic parameters such as water salinity. In this study, catfish Cathorops spixii were evaluated concerning the total arsenic (As) concentration in the muscle tissues of individuals subjected to different abiotic conditions in the Cananéia-Iguape Estuarine-Lagoon Complex (CIELC), which was recently included on the Ramsar list of wetlands of international importance. Seventy-four catfish were seasonally caught in the northern and southern regions of the CIELC and their hydrochemical parameters were obtained. C. spixii from the southern, best preserved, area showed arsenic concentrations around ten times higher than the maximum limit established for fish intended for human consumption. However, these high concentrations of arsenic could be associated with the abiotic parameters of the water, such as salinity variations, in this area.
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Arsénico , Bagres , Contaminantes Químicos del Agua , Humanos , Animales , Bagres/fisiología , Brasil , Estaciones del Año , Metales , Contaminantes Químicos del Agua/análisis , Monitoreo del AmbienteRESUMEN
The composition of seaweeds is complex, with vitamins, phenolic compounds, minerals, and polysaccharides being some of the factions comprising their structure. The main polysaccharide in brown seaweeds is fucoidan, and several biological activities have been associated with its structure. Chitosan is another marine biopolymer that is very popular in the biomedical field, owing to its suitable features for formulating drug delivery systems and, particularly, particulate systems. In this work, the ability of fucoidan to produce nanoparticles was evaluated, testing different amounts of a polymer and using chitosan as a counterion. Nanoparticles of 200-300 nm were obtained when fucoidan prevailed in the formulation, which also resulted in negatively charged nanoparticles. Adjusting the pH of the reaction media to 4 did not affect the physicochemical characteristics of the nanoparticles. The IC50 of fucoidan was determined, in both HCT-116 and A549 cells, to be around 160 µg/mL, whereas it raised to 675-100 µg/mL when nanoparticles (fucoidan/chitosan = 2/1, w/w) were tested. These marine materials (fucoidan and chitosan) provided features suitable to formulate polymeric nanoparticles to use in biomedical applications.
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Quitosano , Fucus , Nanopartículas , Algas Marinas , Sulfatos , Fucus/química , Quitosano/química , Polisacáridos/química , Nanopartículas/químicaRESUMEN
Polyglutamine diseases are a group of neurodegenerative disorders caused by an abnormal expansion of CAG repeat tracts in the codifying regions of nine, otherwise unrelated, genes. While the protein products of these genes are suggested to play diverse cellular roles, the pathogenic mutant proteins bearing an expanded polyglutamine sequence share a tendency to self-assemble, aggregate and engage in abnormal molecular interactions. Understanding the shared paths that link polyglutamine protein expansion to the nervous system dysfunction and the degeneration that takes place in these disorders is instrumental to the identification of targets for therapeutic intervention. Among polyglutamine diseases, spinocerebellar ataxias (SCAs) share many common aspects, including the fact that they involve dysfunction of the cerebellum, resulting in ataxia. Our work aimed at exploring a putative new therapeutic target for the two forms of SCA with higher worldwide prevalence, SCA type 2 (SCA2) and type 3 (SCA3), which are caused by expanded forms of ataxin-2 (ATXN2) and ataxin-3 (ATXN3), respectively. The pathophysiology of polyglutamine diseases has been described to involve an inability to properly respond to cell stress. We evaluated the ability of GTPase-activating protein-binding protein 1 (G3BP1), an RNA-binding protein involved in RNA metabolism regulation and stress responses, to counteract SCA2 and SCA3 pathology, using both in vitro and in vivo disease models. Our results indicate that G3BP1 overexpression in cell models leads to a reduction of ATXN2 and ATXN3 aggregation, associated with a decrease in protein expression. This protective effect of G3BP1 against polyglutamine protein aggregation was reinforced by the fact that silencing G3bp1 in the mouse brain increases human expanded ATXN2 and ATXN3 aggregation. Moreover, a decrease of G3BP1 levels was detected in cells derived from patients with SCA2 and SCA3, suggesting that G3BP1 function is compromised in the context of these diseases. In lentiviral mouse models of SCA2 and SCA3, G3BP1 overexpression not only decreased protein aggregation but also contributed to the preservation of neuronal cells. Finally, in an SCA3 transgenic mouse model with a severe ataxic phenotype, G3BP1 lentiviral delivery to the cerebellum led to amelioration of several motor behavioural deficits. Overall, our results indicate that a decrease in G3BP1 levels may be a contributing factor to SCA2 and SCA3 pathophysiology, and that administration of this protein through viral vector-mediated delivery may constitute a putative approach to therapy for these diseases, and possibly other polyglutamine disorders.
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Enfermedad de Machado-Joseph , Ataxias Espinocerebelosas , Humanos , Ratones , Animales , ADN Helicasas/metabolismo , Proteínas de Choque Térmico , Agregado de Proteínas , Gránulos de Estrés , Proteínas de Unión a Poli-ADP-Ribosa/genética , ARN Helicasas/genética , ARN Helicasas/metabolismo , Proteínas con Motivos de Reconocimiento de ARN/genética , Ataxias Espinocerebelosas/genética , Ataxias Espinocerebelosas/patología , Ataxina-3/genética , Ratones Transgénicos , Enfermedad de Machado-Joseph/genéticaRESUMEN
Spinocerebellar ataxia type 2 (SCA2) is a rare autosomal, dominantly inherited disease, in which the affected individuals have a disease onset around their third life decade. The molecular mechanisms underlying SCA2 are not yet completely understood, for which we hypothesize that aging plays a role in SCA2 molecular pathogenesis. In this study, we performed a striatal injection of mutant ataxin-2 mediated by lentiviral vectors, in young and aged animals. Twelve weeks post-injection, we analyzed the striatum for SCA2 neuropathological features and specific aging hallmarks. Our results show that aged animals had a higher number of mutant ataxin-2 aggregates and more neuronal marker loss, compared to young animals. Apoptosis markers, cleaved caspase-3, and cresyl violet staining also indicated increased neuronal death in the aged animal group. Additionally, mRNA levels of microtubule-associated protein 1 light-chain 3B (LC3) and sequestosome-1 (SQSTM1/p62) were altered in the aged animal group, suggesting autophagic pathway dysfunction. This work provides evidence that aged animals injected with expanded ataxin-2 had aggravated SCA2 disease phenotype, suggesting that aging plays an important role in SCA2 disease onset and disease progression.
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Ataxina-2 , Ataxias Espinocerebelosas , Animales , Ataxina-2/genética , Ataxina-2/metabolismo , Ataxina-3/genética , Caspasa 3/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , ARN Mensajero , Proteína Sequestosoma-1/genética , Proteína Sequestosoma-1/metabolismo , Ataxias Espinocerebelosas/patologíaRESUMEN
Microorganisms have a limited and highly adaptable repertoire of genes capable of encoding proteins containing single or variable multidomains. The phytopathogenic bacteria Xanthomonas citri subsp. citri (X. citri) (Xanthomonadaceae family), the etiological agent of Citrus Canker (CC), presents a collection of multidomain and multifunctional enzymes (MFEs) that remains to be explored. Recent studies have shown that multidomain enzymes that act on the metabolism of the peptidoglycan and bacterial cell wall, belonging to the Lytic Transglycosylases (LTs) superfamily, play an essential role in X. citri biology. One of these LTs, named XAC4296, apart from the Transglycosylase SLT_2 and Peptidoglycan binding-like domains, contains an unexpected aldose 1-epimerase domain linked to the central metabolism; therefore, resembling a canonical MFE. In this work, we experimentally characterized XAC4296 revealing its role as an MFE and demonstrating its probable gene fusion origin and evolutionary history. The XAC4296 is expressed during plant-pathogen interaction, and the Δ4296 mutant impacts CC progression. Moreover, Δ4296 exhibited chromosome segregation and cell division errors, and sensitivity to ampicillin, suggesting not only LT activity but also that the XAC4296 may also contribute to resistance to ß-lactams. However, both Δ4296 phenotypes can be restored when the mutant is supplemented with sucrose or glutamic acid as a carbon and nitrogen source, respectively; therefore, supporting the epimerase domain's functional relationship with the central carbon and cell wall metabolism. Taken together, these results elucidate the role of XAC4296 as an MFE in X. citri, also bringing new insights into the evolution of multidomain proteins and antimicrobial resistance in the Xanthomonadaceae family.
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Spinocerebellar ataxia type 2 (SCA2) is an incurable and genetic neurodegenerative disorder. The disease is characterized by progressive degeneration of several brain regions, resulting in severe motor and non-motor clinical manifestations. The mutation causing SCA2 disease is an abnormal expansion of CAG trinucleotide repeats in the ATXN2 gene, leading to a toxic expanded polyglutamine segment in the translated ataxin-2 protein. While the genetic cause is well established, the exact mechanisms behind neuronal death induced by mutant ataxin-2 are not yet completely understood. Thus, the goal of this study is to investigate the role of autophagy in SCA2 pathogenesis and investigate its suitability as a target for therapeutic intervention. For that, we developed and characterized a new striatal lentiviral mouse model that resembled several neuropathological hallmarks observed in SCA2 disease, including formation of aggregates, neuronal marker loss, cell death and neuroinflammation. In this new model, we analyzed autophagic markers, which were also analyzed in a SCA2 cellular model and in human post-mortem brain samples. Our results showed altered levels of SQSTM1 and LC3B in cells and tissues expressing mutant ataxin-2. Moreover, an abnormal accumulation of these markers was detected in SCA2 patients' striatum and cerebellum. Importantly, the molecular activation of autophagy, using the compound cordycepin, mitigated the phenotypic alterations observed in disease models. Overall, our study suggests an important role for autophagy in the context of SCA2 pathology, proposing that targeting this pathway could be a potential target to treat SCA2 patients.
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Autofagia/genética , Ataxias Espinocerebelosas/genética , Ataxias Espinocerebelosas/terapia , Animales , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Ratones , TransfecciónRESUMEN
Polyglutamine spinocerebellar ataxias (PolyQ SCAs) are a group of 6 rare autosomal dominant diseases, which arise from an abnormal CAG repeat expansion in the coding region of their causative gene. These neurodegenerative ataxic disorders are characterized by progressive cerebellar degeneration, which translates into progressive ataxia, the main clinical feature, often accompanied by oculomotor deficits and dysarthria. Currently, PolyQ SCAs treatment is limited only to symptomatic mitigation, and no therapy is available to stop or delay the disease progression, which culminates with death. Over the last years, many promising gene therapy approaches were investigated in preclinical studies and could lead to a future treatment to stop or delay the disease development. Here, we summed up the most promising of these therapies, categorizing them in gene augmentation therapy, gene silencing strategies, and gene edition approaches. While several of the reviewed strategies are promising, there is still a gap from the preclinical results obtained and their translation to clinical studies. However, there is an increase in the number of approved gene therapies, as well as a constant development in their safety and efficacy profiles. Thus, it is expected that in a near future some of the promising strategies reviewed here could be tested in a clinical setting and if successful provide hope for SCAs patients.
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Terapia Genética/métodos , Péptidos/metabolismo , Ataxias Espinocerebelosas/terapia , Edición Génica , Silenciador del Gen/fisiología , Humanos , Ataxias Espinocerebelosas/genéticaRESUMEN
Citrus canker type A is a serious disease caused by Xanthomonas citri subsp. citri (X. citri), which is responsible for severe losses to growers and to the citrus industry worldwide. To date, no canker-resistant citrus genotypes are available, and there is limited information regarding the molecular and genetic mechanisms involved in the early stages of the citrus canker development. Here, we present the CitrusKB knowledge base. This is the first in vivo interactome database for different citrus cultivars, and it was produced to provide a valuable resource of information on citrus and their interaction with the citrus canker bacterium X. citri. CitrusKB provides tools for a user-friendly web interface to let users search and analyse a large amount of information regarding eight citrus cultivars with distinct levels of susceptibility to the disease, with controls and infected plants at different stages of infection by the citrus canker bacterium X. citri. Currently, CitrusKB comprises a reference citrus genome and its transcriptome, expressed transcripts, pseudogenes and predicted genomic variations (SNPs and SSRs). The updating process will continue over time by the incorporation of novel annotations and analysis tools. We expect that CitrusKB may substantially contribute to the field of citrus genomics. CitrusKB is accessible at http://bioinfo.deinfo.uepg.br/citrus. Users can download all the generated raw sequences and generated datasets by this study from the CitrusKB website.
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Citrus , Citrus/genética , Bases del Conocimiento , Enfermedades de las Plantas/genética , Transcriptoma/genética , XanthomonasRESUMEN
The clinical manifestations of non-Hodgkin's lymphomas (NHL) are unspecific and may vary with their location, growth rate or organs involved. Chylothorax consists of an accumulation of chyle in pleural space. galiLymphoproliferative diseases represent the main non-traumatic aetiology. The authors report the case of an 81-year-old woman admitted with right pleural effusion and lower limbs oedema, initially interpreted as decompensated heart failure. The thoracocentesis revealed a chylothorax and the aetiological study exposed a mantle cell lymphoma. The authors aim to alert to a less frequent presentation of NHL and remind that a low suspicion may delay the diagnosis
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Humanos , Femenino , Anciano de 80 o más Años , Linfoma de Células del Manto/patología , Quilotórax/diagnóstico por imagen , Toracocentesis/métodos , Quilo/fisiología , Disnea/etiología , Edema/etiología , Fatiga/etiología , Biopsia/métodosRESUMEN
BACKGROUND: The objectives of this study were to investigate the relationships between polymorphisms at the interferon lambda (IFNL) locus and CD4+:CD8+ ratio normalisation in people living with HIV (PLWH) on effective antiretroviral therapy (ART); and to examine whether these polymorphisms influence the composition of T lymphocyte compartments in long-term treated HIV-1 infection. METHODS: A cross-sectional study in PLWH enrolled into the Mater Immunology study. We performed IFNL genotyping on stored samples and evaluated the association of IFNL single-nucleotide polymorphisms (rs368234815 and rs12979860) with CD4+:CD8+ ratio normalization (> 1) and expanded CD4+ and CD8+ T-cell subsets; CD45RO+CD62L+ (central-memory), CD45RO+ CD62L-(effector-memory) and CD45RO-CD62L+ (naïve), using logistic and linear regression models, respectively. RESULTS: 190 ambulatory PLWH recruited to the main study, 143 were included in the analysis (38 had no stored DNA and 9 no T-lymphocyte subpopulation). Of 143 included, the median age (IQR) was 45(39-48) years, 64% were male and 66% were of Caucasian ethnicity. Heterosexual-contact (36%), injecting drug-use (33%) and men who have sex with men (24%) were the most presented HIV-transmission risk groups. The majority of subjects (90.2%) were on ART with 79% of the cohort having an undetectable HIV-RNA (< 40 copies/ml) and the time since ART initiation was 7.5 (3.7-10.4) year. rs368234815 and rs12979860 displayed similar allelic frequencies, with minor alleles ΔG and T representing 39% and 42%, respectively, of circulating alleles. rs368234815 ΔG/ΔG minor homozygotes were significantly associated with increased odds for attaining a normalised CD4+:CD8+ ratio compared to rs368234815 T/T major homozygotes in PLWH virologically suppressed on effective ART (OR = 3.11; 95% CI [1.01:9.56]). rs368234815 ΔG/ΔG homozygosity was also significantly associated with lower levels of CD4+ effector memory T-cells (regression coefficient: - 7.1%, p = 0.04) and CD8+ naïve T-cell subsets were significantly higher in HIV-1 mono-infected PLWH with rs368234815 ΔG/ΔG (regression coefficient: + 7.2%, p = 0.04). CONCLUSIONS: In virally-suppressed, long-term ART-treated PLWH, rs368234815 ΔG/ΔG homozygotes were more likely to have attained normalisation of their CD4+:CD8+ ratio, displayed lower CD4+ effector memory and higher naive CD8+ T-cells. Further studies are needed to replicate our findings in other, larger and more diverse cohorts and to determine the impact of IFNL genetic-variation on CD4+:CD8+ ratio normalisation and clinical outcomes in PLWH.
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Fármacos Anti-VIH/uso terapéutico , Relación CD4-CD8 , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , Interferones/genética , Adulto , Alelos , Estudios de Cohortes , Estudios Transversales , Femenino , Genotipo , Infecciones por VIH/inmunología , VIH-1 , Homosexualidad Masculina , Humanos , Memoria Inmunológica , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Respuesta Virológica Sostenida , Carga Viral/efectos de los fármacosRESUMEN
BACKGROUND: CD6 is a lymphocyte surface co-receptor physically associated with the T-cell receptor (TCR)/CD3 complex at the center of the immunological synapse. There, CD6 assists in cell-to-cell contact stabilization and modulation of activation/differentiation events through interaction with CD166/ALCAM (activated leukocyte cell adhesion molecule), its main reported ligand. While accumulating evidence is attracting new interest on targeting CD6 for therapeutic purposes in autoimmune disorders, little is known on its potential in cancer. In an attempt to elucidate the in vivo relevance of blocking CD6-mediated interactions in health and disease, we explored the consequences of expressing high circulating levels of a soluble form CD6 (sCD6) as a decoy receptor. METHODS: High sCD6 serum levels were achieved by using transgenic C57BL/6 mice expressing human sCD6 under the control of lymphoid-specific transcriptional elements (shCD6LckEµTg) or wild type either transduced with hepatotropic adeno-associated virus coding for mouse sCD6 or undergoing repeated infusions of recombinant human sCD6 protein. Characterization of sCD6-induced changes was performed by ex vivo flow cytometry and functional analyses of mouse lymphoid organ cells. The in vivo relevance of those changes was explored by challenging mice with subcutaneous or metastatic tumors induced by syngeneic cancer cells of different lineage origins. RESULTS: Through a combination of in vitro and in vivo studies, we show that circulating sCD6 expression induces defective regulatory T cell (Treg) generation and function, decreased CD166/ALCAM-mediated tumor cell proliferation/migration and impaired galectin-induced T-cell apoptosis, supporting the fact that sCD6 modulates antitumor lymphocyte effector function and tumorigenesis. Accordingly, sCD6 expression in vivo resulted in delayed subcutaneous tumor growth and/or reduced metastasis on challenge of mice with syngeneic cancer cells. CONCLUSIONS: Evidence is provided for the disruption of CD6 receptor-ligand interactions as a feasible immunomodulatory approach in cancer.
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Antígenos CD/sangre , Antígenos de Diferenciación de Linfocitos T/sangre , Neoplasias Pulmonares/inmunología , Linfoma de Células T/inmunología , Melanoma Experimental/inmunología , Sarcoma Experimental/inmunología , Linfocitos T Reguladores/inmunología , Molécula de Adhesión Celular del Leucocito Activado/inmunología , Molécula de Adhesión Celular del Leucocito Activado/metabolismo , Animales , Antígenos CD/administración & dosificación , Antígenos CD/biosíntesis , Antígenos CD/genética , Antígenos de Diferenciación de Linfocitos T/administración & dosificación , Antígenos de Diferenciación de Linfocitos T/biosíntesis , Antígenos de Diferenciación de Linfocitos T/genética , Apoptosis/fisiología , Diferenciación Celular/fisiología , Línea Celular Tumoral , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Linfoma de Células T/metabolismo , Masculino , Melanoma Experimental/sangre , Melanoma Experimental/patología , Melanoma Experimental/terapia , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/sangre , Proteínas Recombinantes/genética , Sarcoma Experimental/sangre , Sarcoma Experimental/patología , Linfocitos T Reguladores/metabolismoRESUMEN
RESUMEN Introducción: La interpretación de la prueba de esfuerzo cardiopulmonar (PECP) en cardiopatías congénitas representa un desafío, ya que estas constituyen un grupo amplio con diferentes grados de gravedad. Objetivos: Obtener en nuestro centro valores de referencia para las variables medidas mediante la PECP en adolescentes y adultos con cardiopatías congénitas, con el objetivo de poder comparar entre pares los resultados esperados de la PECP según edad, sexo e igual patología. Material y Métodos: Se realizaron 799 PECP en 473 pacientes mayores de 17 años con distintas cardiopatías. Variables estudiadas: VO2 pico (ml/kg/min), % predicho de VO2 pico, duración en segundos de la prueba (discriminada por sexo), VE/VCO2 slope y coeficiente R para el total de las pruebas. Análisis estadístico: media y desvío estándar para cada variable, T test para las estudiadas por sexo. Resultados: El VO2 pico (ml/kg/min), el % predicho del VO2 pico y la duración de la prueba disminuyeron conforme aumentó la gravedad de la cardiopatía. El % predicho de VO2 pico corrige los valores de VO2 ml/kg/min por edad y sexo, por lo que constituye un dato más útil para la evaluación. El coeficiente R mayor que 1,1 indica que los pacientes realizaron una prueba máxima. El VE/VCO2 slope está aumentado en las cardiopatías graves. Conclusiones: Los valores de referencia de la PECP para las distintas cardiopatías congénitas son fundamentales, pues nos permiten comparar pacientes con igual patología. El % predicho de VO2 pico parece ser el dato más útil para este fin.
SUMMARY Background: The interpretation of cardiopulmonary exercise testing (CPET) in congenital heart diseases represents a challenge, since they constitute a large group of anomalies with different degrees of severity. Objectives: The aim of this study was to obtain reference values of CPET variables in adolescents and adults with congenital heart diseases in our center, to compare between peers the expected results of CPET according to age, gender and the same pathology. Methods: A total of 799 tests were performed in 473 patients older than 17 years with different congenital heart diseases. Variables studied were peak VO2 (ml/kg/min), percent-predicted peak VO2, test duration in seconds (discriminated by gender), VE/VCO2 slope and R coefficient for all the tests. Statistical analyses were conducted using mean and standard deviation for each variable and Student's t test for those studied by gender. Results: Peak VO2 (ml/kg/min), percent-predicted peak VO2, and test duration decreased as the severity of heart diseases increased. The percent-predicted peak VO2 corrects VO2 ml/kg/min values for age and sex, so it becomes a more useful variable for evaluation. An R coefficient greater than 1.1 indicates that patients performed a maximal test. The VE/VCO2 slope is increased in severe heart diseases. Conclusions: Reference CPET values for the different congenital heart diseases are essential, since they allow us to compare patients with the same pathology. The percent-predicted peak VO2 seems to be the most useful variable for this purpose.
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The ecosystem services approach can inform decision-making by accounting for both short- and long-term benefits from different land use options. Here we used the InVEST toolkit to quantify and map key ecosystem services at the largest publicly-owned agro-silvo-pastoral farmstead in Portugal-a site representative for the montado landscape. We analyzed how Provisioning (cork production) and Regulating & Maintenance (carbon storage and sequestration) services would be affected under three land use change scenarios, which were developed in collaboration with the forest manager of the study area: Cattle Intensification, Forest Improvement, and Residential Development. Results show that increasing cattle or residential development would deliver substantially lower levels of services. We find that extensive management, improvements to forest quality, and promotion of traditional livestock grazing would provide the highest levels of assessed ecosystem services, resulting in 13.5% more carbon storage (worth between $0.34-$7.79 million USD depending on carbon price) and 62.7% more cork production (total value of USD $3.5 million) than the current land use. However, a shift in economic incentives to make sustainable cork harvesting and traditional low-density grazing of smaller ruminants like sheep and goats profitable are likely needed to reward traditional land stewardship and help support this iconic Mediterranean landscape in the future.
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Agricultura/métodos , Conservación de los Recursos Naturales/métodos , Agricultura Forestal/métodos , Animales , Carbono/análisis , Bovinos , Ecosistema , Bosques , Ganado , Recursos Naturales , Portugal , Quercus/crecimiento & desarrollo , Ovinos , Árboles/crecimiento & desarrolloRESUMEN
Individual susceptibility differences to fungal infection following invasive and/or immunosuppressive medical interventions are an important clinical issue. In order to explore immune response-related factors that may be linked to fungal infection susceptibility, we have compared the response of inbred C57BL/6J and outbred CD1 mouse strains to different experimental models of fungal sepsis. The challenge of animals with the zymosan-induced generalised inflammation model revealed poorer survival rates in C57BL/6J, consistent with lower Th1 cytokine interferon (IFN)-γ serum levels, compared with CD1 mice. Likewise, ex vivo exposure of C57BL/6J splenocytes to zymosan but also bacterial lipopolisaccharide or lipoteichoic acid, resulted in lower IFN-γ secretion compared with CD1 mice. C57BL/6J susceptibility could be reverted by rescue infusion of relative low IFN-γ doses (0.2 µg/kg) either alone or in combination with the ß-glucan-binding CD5 protein (0.7 mg/kg) leading to improved post zymosan-induced generalised inflammation survival. Similarly, low survival rates to systemic Candida albicans infection (2.86 × 104 CFU/gr) were ameliorated by low-dose IFN-γ infusion in C57BL/6J but not CD1 mice. Our results highlight the importance of strain choice in experimental fungal infection models and provide a susceptibility rationale for more specific antifungal immunotherapy designs.
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Candidiasis/inmunología , Susceptibilidad a Enfermedades/inmunología , Interferón gamma/uso terapéutico , Micosis/inmunología , Sepsis/inmunología , Animales , Animales no Consanguíneos , Proteínas de la Membrana Bacteriana Externa/inmunología , Antígenos CD5/administración & dosificación , Candida albicans/inmunología , Candida albicans/patogenicidad , Candidiasis/tratamiento farmacológico , Citocinas/sangre , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades/microbiología , Interferón gamma/administración & dosificación , Interferón gamma/sangre , Lipopolisacáridos/toxicidad , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Micosis/tratamiento farmacológico , Sepsis/tratamiento farmacológico , Sepsis/microbiología , Sepsis/mortalidad , Especificidad de la Especie , Bazo/citología , Bazo/efectos de los fármacos , Bazo/metabolismo , Ácidos Teicoicos/toxicidad , Zimosan/toxicidadRESUMEN
Xanthomonas citri subsp. citri 306 (XccA) is the causal agent of type A citrus canker (CC), one of the most significant citriculture diseases. Murein lytic transglycosylases (LT), potentially involved in XccA pathogenicity, are enzymes responsible for peptidoglycan structure assembly, remodeling and degradation. They directly impact cell wall expansion during bacterial growth, septum division allowing cell separation, cell wall remodeling allowing flagellar assembly, bacterial conjugation, muropeptide recycling, and secretion system assembly, in particular the Type 3 Secretion System involved in bacterial virulence, which play a fundamental role in XccA pathogenicity. Information about the XccA LT arsenal is patchy: little is known about family diversity, their exact role or their connection to virulence in this bacterium. Among the LTs with possible involvement in virulence, two paralogue open reading frames (ORFs) (one on the chromosome and one in plasmid pXAC64) are passenger genes of the Tn3 family transposon TnXax1, known to play a significant role in the evolution and emergence of pathogenicity in Xanthomonadales and to carry a variety of virulence determinants. This study addresses LT diversity in the XccA genome and examines the role of plasmid and chromosomal TnXax1 LT passenger genes using site-directed deletion mutagenesis and functional characterization. We identified 13 XccA LTs: 12 belong to families 1A, 1B, 1C, 1D (two copies), 1F, 1G, 3A, 3B (two copies), 5A, 6A and one which is non-categorized. The non-categorized LT is exclusive to the Xanthomonas genus and related to the 3B family but contains an additional domain linked to carbohydrate metabolism. The categorized LTs are probably involved in cell wall remodeling to allow insertion of type 3, 4 and 6 secretion systems, flagellum assembly, division and recycling of cell wall and degradation and control of peptidoglycan production. The TnXax1 passenger LT genes (3B family) are not essential to XccA or for CC development but are implicated in peptidoglycan metabolism, directly impacting bacterial fitness and CC symptom enhancement in susceptible hosts (e.g., Citrus sinensis). This underlines the role of TnXax1 as a virulence and pathogenicity-propagating agent in XccA and suggests that LT acquisition by horizontal gene transfer mediated by TnXax1 may improve bacterial fitness, conferring adaptive advantages to the plant-pathogen interaction process.
RESUMEN
An elective laparoscopic ovariectomy on a healthy dog revealed a cystic structure in the left ovary. The surgical procedure was successful. Histopathological examination showed the presence of a teratoma adjacent to the ovary. To the best of the authors' knowledge, this is the ï¬rst reported case of an ovarian teratoma removed by laparoscopic ovariectomy in a dog by using a multiport laparoscopic ovariectomy technique.