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1.
Sci Data ; 11(1): 782, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39013892

RESUMO

We present a flora and fauna dataset for the Mira-Mataje binational basins. This is an area shared between southwestern Colombia and northwestern Ecuador, where both the Chocó and Tropical Andes biodiversity hotspots converge. We systematized data from 120 sources in the Darwin Core Archive (DwC-A) standard and geospatial vector data format for geographic information systems (GIS) (shapefiles). Sources included natural history museums, published literature, and citizen science repositories across 13 countries. The resulting database has 33,460 records from 6,821 species, of which 540 have been recorded as endemic, and 612 as threatened. The diversity represented in the dataset is equivalent to 10% of the total plant species and 26% of the total terrestrial vertebrate species in both hotspots. The dataset can be used to estimate and compare biodiversity patterns with environmental parameters and provide value to ecosystems, ecoregions, and protected areas. The dataset is a baseline for future assessments of biodiversity in the face of environmental degradation, climate change, and accelerated extinction processes.


Assuntos
Biodiversidade , Plantas , Equador , Animais , Colômbia , Vertebrados , Sistemas de Informação Geográfica , Ecossistema , Mudança Climática , Conservação dos Recursos Naturais , Clima Tropical
2.
Curr Issues Mol Biol ; 46(4): 3424-3437, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38666945

RESUMO

Escherichia coli phytase (AppA) is widely used as an exogenous enzyme in monogastric animal feed mainly because of its ability to degrade phytic acid or its salt (phytate), a natural source of phosphorus. Currently, successful recombinant production of soluble AppA has been achieved by gene overexpression using both bacterial and yeast systems. However, some methods for the biomembrane immobilization of phytases (including AppA), such as surface display on yeast cells and bacterial spores, have been investigated to avoid expensive enzyme purification processes. This study explored a homologous protein production approach for displaying AppA on the cell surface of E. coli by engineering its outer membrane (OM) for extracellular expression. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of total bacterial lysates and immunofluorescence microscopy of non-permeabilized cells revealed protein expression, whereas activity assays using whole cells or OM fractions indicated functional enzyme display, as evidenced by consistent hydrolytic rates on typical substrates (i.e., p-nitrophenyl phosphate and phytic acid). Furthermore, the in vitro results obtained using a simple method to simulate the gastrointestinal tract of poultry suggest that the whole-cell biocatalyst has potential as a feed additive. Overall, our findings support the notion that biomembrane-immobilized enzymes are reliable for the hydrolysis of poorly digestible substrates relevant to animal nutrition.

3.
Mycoses ; 67(1): e13669, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37946667

RESUMO

BACKGROUND: The natural history of candidemia in kidney transplant recipients (KTR) remains poorly understood. This study aimed to evaluate mortality, prognostic factors and overall graft loss after candidemia in KTRs. METHODS: This is a retrospective multicentre study enrolling all KTRs ≥15 years old with candidemia diagnosed at hospitals in Brazil, Spain and Italy from 2010 to 2020. Primary endpoints were mortality rates at 14 and 30 days. Secondary endpoints were prognostic factors of 14-day mortality and overall graft loss. RESULTS: We enrolled 93 KTRs of which 75 were from Brazil. The mean time interval from transplantation to the onset of candidemia was 45.2 ± 61.5 months. 42% of all patients were on haemodialysis, 31.3% had an episode of sepsis and 39% underwent surgery within 30 days before fungemia. European patients were more likely to receive echinocandin (32 vs. 72%, p < .001). 22.7% of Brazilian patients did not receive any antifungal before death. All-cause mortality at 14 days was higher in Brazil (41.3 vs. 11.1%, p = .016). Candida colonisation (OR 6.91 [95% CI: 1.08-44.3], p = .042) and hypotension (OR 4.87 [95% CI: 1.62-14.66], p = .005) were associated with 14-day mortality. Echinocandin treatment had a protective effect (OR 0.19 [95% CI: 0.05-0.73], p = .015). Graft loss at 90 days occurred in 48% of patients (70.7 in Brazil vs. 22.2% in Europe, p < .01). CONCLUSIONS: Candidemia in KTR is usually documented late after engraftment in patients requiring HD, surgical procedures and dysbiosis secondary to antibiotic use. Mortality was higher in Brazil. Echinocandin therapy was associated with improved survival.


Assuntos
Candidemia , Transplante de Rim , Adolescente , Humanos , Antifúngicos/uso terapêutico , Candidemia/tratamento farmacológico , Candidemia/epidemiologia , Candidemia/microbiologia , Equinocandinas/uso terapêutico , Transplante de Rim/efeitos adversos , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto
4.
Horiz. enferm ; (Número especial: Investigación y práctica en condiciones crónicas de salud): 43-59, 28 dic. 2023. tab, ilus
Artigo em Espanhol | LILACS-Express | LILACS, BDENF - Enfermagem, MINSALCHILE | ID: biblio-1553321

RESUMO

INTRODUCCIÓN: La carga de cuidado en los cuidadores familiares (CF), tiene un efecto en la salud física y mental, relaciones familiares, laborales y estado financiero, aumentando la necesidad de intervenciones efectivas para mejorar el automanejo de su condición y el cuidado al familiar en el hogar. OBJETIVO: evaluar la efectividad de un programa para promover el automanejo en CF. METODOLOGÍA: de diseño cuasi experimental con mediciones pre y post intervención, en una muestra no probabilística, intencionada de 19 CF de personas mayores con nivel de dependencia. El programa "Trabajando juntos en colaboración" (TJC), implementado por facilitadores entrenados y certificados, promueve el automanejo y habilidades para cuidar a su familiar en casa. Para evaluar el efecto de la intervención se aplicó pre y post-test el Instrumento de "Automanejo en Cuidadores Familiares", la prueba Shapiro-Wilks, el análisis de diferencias por la t-Student y test de Wilcoxon, se calculó el tamaño del efecto y la potencia estadística (1- ß). RESULTADOS: se encontró una diferencia estadísticamente significativa entre el pre y post intervención, observando un incremento en el resultado de la sumatoria global y en las tres dimensiones del automanejo. Estas diferencias muestran un efecto relevante a considerar (>,80) y una potencia alta (>,80). CONCLUSIÓN: El Programa TJC, muestra efectividad en mejorar el automanejo en CF, con una potencia adecuada que podría permitir generalizar resultados en poblaciones similares. Siendo este un programa genérico, podría ser aplicado en cualquier caso de CF, independiente a la enfermedad o condición de su familiar.


INTRODUCTION: The caregiving burden on family caregivers (FC) has an impact on physical and mental health, family relationships, work, and financial status, increasing the need for effective interventions to improve self-management of their condition and care for the family member at home. OBJECTIVE: to evaluate the effectiveness of a program to promote self-management in FC. METHODOLOGY: The study employed a quasi-experimental design with pre- and post-intervention measurements in a non-probabilistic, purposive sample of 19 FC of older individuals with a level of dependency. The "Trabajando Juntos en Colaboración" (TJC) program, implemented by trained and certified facilitators, promotes self-management and skills to care for their family member at home. To assess the intervention's effect, pre and post-tests were administered using the "Automanejo en Cuidadores Familiares" instrument, along with the Shapiro-Wilks test, t-Student analysis of differences, and Wilcoxon test. Effect size and statistical power (1- ß) were calculated. RESULTS: indicated statistically significant differences between the pre- and post-intervention periods, with an observed increase in the overall sum and in all three dimensions of self-management. These differences demonstrate a relevant effect (>0.80) and high statistical power (>0.80). CONCLUSION: the TJC program proves effective in enhancing self-management in CF, with sufficient power to potentially generalize results to similar populations. As a generic program, it could be applied in any FC case, regardless of the disease or condition of their family member.

5.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1535407

RESUMO

Introducción: La pandemia por COVID-19 trajo consigo grandes cambios a nivel socioeconómico, producto de las medidas tomadas para mitigar su expansión, que implicó cierre de colegios y dificultad para el acceso a servicios de salud. Sin embargo, no se cuenta con mucha información respecto al impacto que estas medidas han tenido en la salud y el bienestar de niños y adolescentes, por lo cual se desarrolló una encuesta virtual para conocer la dimensión de los efectos de la pandemia en el bienestar integral de los menores y sus familias. Metodología: Estudio observacional de corte transversal que se realizó mediante la aplicación de una encuesta en formato electrónico a padres de familia de niños y adolescentes del Área Metropolitana de Bucaramanga. Resultados: Se obtuvieron 960 respuestas. El 25,63 % de los encuestados refieren cancelación de citas médicas. El 98 % de los estudiantes pudo continuar las actividades académicas durante el aislamiento. El factor económico fue la principal causa de preocupación en el periodo de la encuesta. Discusión: Durante el periodo de aislamiento, los problemas de salud mental, las dificultades para el acceso a herramientas para la educación virtual y las barreras para la atención, propias de la emergencia sanitaria, causaron efectos significativos en la calidad de vida de los menores. Conclusiones: Ante emergencias sanitarias, se deben mantener los servicios de atención en salud de la misma forma que se hacía previo a la ocurrencia del evento, como los programas de vacunación, crecimiento y desarrollo, promoción y prevención, además de la continuidad de la escolaridad.


Introduction: The COVID-19 pandemic has brought great changes along with, some of those were at the socioeconomic level, as a result of the actions taken to mitigate the virus expansion, which involved the closure of schools and restriction in accessing to some health services. However, there is not much information regarding the impact that these measures have had on the health and well-being of children and adolescents, for this reason, a virtual survey was developed to find out the dimension of the pandemic's effect on the comprehensive welfare of minors and families. Methodology: Cross-sectional observational study, which was carried out by applying a survey in electronic format to parents of children and adolescents in the Metropolitan Area of Bucaramanga. Results: A total of 960 responses were obtained. Of those surveyed, 25,63% refer cancellation of medical appointments. The 98% of students were able to continue academic activities during isolation. The economic factor was the main cause of concern in the survey period. Discussion: During the isolation period, mental health problems, difficulties in accessing tools for virtual education and barriers to care, typical of the health emergency, caused a significant effects on the quality of life of youngsters. Conclusions: In the event of health emergencies, health care services should be maintained in the same way as before the occurrence of the event, such as vaccination, growth and development, promotion and prevention programs, in addition to the continuity of schooling.

6.
Int J Mol Sci ; 24(15)2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37569368

RESUMO

TOR proteins, also known as targets of rapamycin, are serine/threonine kinases involved in various signaling pathways that regulate cell growth. The protozoan parasite Giardia lamblia is the causative agent of giardiasis, a neglected infectious disease in humans. In this study, we used a bioinformatics approach to examine the structural features of GTOR, a G. lamblia TOR-like protein, and predict functional associations. Our findings confirmed that it shares significant similarities with functional TOR kinases, including a binding domain for the FKBP-rapamycin complex and a kinase domain resembling that of phosphatidylinositol 3-kinase-related kinases. In addition, it can form multiprotein complexes such as TORC1 and TORC2. These results provide valuable insights into the structure-function relationship of GTOR, highlighting its potential as a molecular target for controlling G. lamblia cell proliferation. Furthermore, our study represents a step toward rational drug design for specific anti-giardiasis therapeutic agents.


Assuntos
Giardia lamblia , Giardíase , Humanos , Sirolimo/farmacologia , Giardia lamblia/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Transdução de Sinais , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo
7.
Neurotox Res ; 41(3): 224-241, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36723781

RESUMO

Causes of dopaminergic neuronal loss in Parkinson's disease (PD) are subject of investigation and the common use of models of acute neurodegeneration induced by neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 6-hydroxydopamine, and rotenone contributed to advances in the study of PD. However, the use of study models more similar to the pathophysiology of PD is required for advances in early diagnosis and translational pharmacology. Aminochrome (AMI), a compound derived from dopamine oxidation and a precursor of neuromelanin, is able to induce all the mechanisms associated with neurodegeneration. Previously, we showed AMI is cytotoxic in primary culture of mesencephalic cells (PCMC) and induces in vitro and in vivo neuroinflammation. On the other hand, the effect of rutin in central nervous system cells has revealed anti-inflammatory, antioxidative, and neuroprotective potential. However, there have been no data studies on the effect of rutin against aminochrome neurotoxicity. Here, we show that rutin prevents lysosomal dysfunction and aminochrome-induced cell death in SHSY-5Y cells, protects PCMC against aminochrome cytotoxicity, and prevents in vivo loss of dopaminergic neurons in substantia nigra pars compacta (SNPc), as well as microgliosis and astrogliosis. Additionally, we show that rutin decreases levels of interleukin-1ß (IL-1ß) mRNA and increases levels of glia-derived neurotrophic factor (GDNF) and nerve-derived neurotrophic factor (NGF) mRNA. We evidence for the first time the protective effect of rutin on PD aminochrome-induced models and suggest the potential role of the anti-inflammatory activity and upregulation of NGF and GDNF in the mechanism of rutin action against aminochrome neurotoxicity.


Assuntos
Fármacos Neuroprotetores , Síndromes Neurotóxicas , Doença de Parkinson , Animais , Camundongos , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Flavonoides/farmacologia , Rutina/farmacologia , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/prevenção & controle , Síndromes Neurotóxicas/metabolismo , Dopamina/metabolismo , Doença de Parkinson/metabolismo , Neurônios Dopaminérgicos , Anti-Inflamatórios/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia
8.
BMC Anesthesiol ; 22(1): 294, 2022 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114460

RESUMO

BACKGROUND: Opioid anesthetic agents can modulate the impaired immune response in obese patients through mechanisms that involve the expression and release of cytokines. For this reason, anesthetic care for obese patients remains controversial. Therefore, the aim of the study was to compare the effect of opioid-containing anesthesia (OCA) vs opioid-free anesthesia (OFA) using the Cortínez-Sepúlveda model on IL-6, IL-1ß and TNF-α serum levels before and after surgery in obese patients undergoing bypass surgery. METHODS: This randomized cross-sectional study conducted among 40 unrelated obese adults was performed in the Civil Hospital of Guadalajara "Dr. Juan I. Menchaca". Before undergoing laparoscopic Roux-en-Y gastric bypass, patients were randomly assigned to two anesthesia groups: OCA (n = 20) or OFA (n = 20). Fentanyl was the opioid used in the OCA group. The Cortínez-Sepúlveda pharmacokinetic model was used to characterize the disposition of intravenous propofol for the target-controlled infusion technique in obese patients. Body mass was determined to the nearest 0.05 kg using a balance scale (Seca 703; Seca, Hamburg, Germany). Blood samples were taken before and immediately after surgery and cytokine concentrations were determined by ELISA. Pain was assessed using a numerical pain rating scale. Adverse effects were collected within the first 24 h after surgery. RESULTS: A total of 6 men and 34 women were included (37.9 ± 10.6 years). Pre-surgery IL-6 and TNF-α serum levels were not detected in study subjects. However, IL-1ß levels significantly decreased after surgery (49.58 pg/mL (18.50-112.20)-before surgery vs 13 pg/mL (5.43-22)-after surgery, p = 0.019). IL-6 concentrations were significantly higher in subjects who received OCA (with fentanyl) compared to subjects with OFA (224.5 pg/mL (186.3-262.8) vs 99.5 pg/mL (60.8-138.2), respectively, p < 0.001; adjusted by age, gender, and BMI). In addition, the use of opioids confers an increased risk for higher IL-6 levels in obese patients (OR = 2.95, 95% CI: 1.2-7.2, p = 0.010). A linear regression model showed that the operative time (in hours) of bypass surgery and anesthetic technique were positively correlated with IL-6 levels. CONCLUSION: Anesthesia with opioids correlated positively with IL-6 serum levels in obese patients undergoing bypass surgery. This finding could have clinical relevance when an appropriate anesthetic management plan is selected for bariatric surgical patients. TRIAL REGISTRATION: The study was retrospectively registered at ClinicalTrials.gov Identification Number: NCT04854252, date 22/04/2021.


Assuntos
Anestesia , Derivação Gástrica , Propofol , Adulto , Analgésicos Opioides/uso terapêutico , Estudos Transversais , Citocinas , Feminino , Fentanila/uso terapêutico , Derivação Gástrica/métodos , Humanos , Interleucina-6 , Masculino , Obesidade/cirurgia , Dor/tratamento farmacológico , Fator de Necrose Tumoral alfa
9.
Neurotox Res ; 40(6): 2135-2147, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35997936

RESUMO

Studies showed that JM-20, a benzodiazepine-dihydropyridine hybrid molecule, protects against rotenone and 6-hydroxydopamine neurotoxicity. However, its protective effects against cytotoxicity induced by endogenous neurotoxins involved in Parkinson's disease (PD) pathogenesis have never been investigated. In this study, we evaluated the ability of JM-20 to inhibit alpha-synuclein (aSyn) aggregation. We also evaluated the interactions of JM-20 with aSyn by molecular docking and molecular dynamics and assessed the protective effect of JM-20 against aminochrome cytotoxicity. We demonstrated that JM-20 induced the formation of heterogeneous amyloid fibrils, which were innocuous to primary cultures of mesencephalic cells. Moreover, JM-20 reduced the average size of aSyn positive inclusions in H4 cells transfected with SynT wild-type and synphilin-1-V5, but not in HEK cells transfected with synphilin-1-GFP. In silico studies showed the interaction between JM-20 and the aSyn-binding site. Additionally, we showed that JM-20 protects SH-SY5Y cells against aminochrome cytotoxicity. These results reinforce the potential of JM-20 as a neuroprotective compound for PD and suggest aSyn as a molecular target for JM-20.


Assuntos
Di-Hidropiridinas , Neuroblastoma , Doença de Parkinson , Humanos , alfa-Sinucleína , Benzodiazepinas , Simulação de Acoplamento Molecular , Doença de Parkinson/tratamento farmacológico
10.
Enferm Infecc Microbiol Clin (Engl Ed) ; 40(5): 262-265, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35577445

RESUMO

INTRODUCTION: SARS-CoV-2variants of concern (VOC) have been described in the UK (B.1.1.7), South Africa (B.1.351) and Brazil (P.1). Among them, the most scarce information has been obtained from the P.1 variant and more data on its global presence and about its spreading dynamics are needed. METHODS: Whole genome sequencing was performed prospectively on travellers arriving from Brazil and on a random selection of SARS-CoV-2 positive cases from our population. RESULTS: In this study we report the first SARS-CoV-2 P.1 and P.2 variants exported from Brazil to Spain. The case infected with the P.1 variant, who had only stayed in Rio de Janeiro, required hospitalisation. The two P.2 cases remained asymptomatic. A wider distribution for P.1 variant beyond the Brazilian Amazonia should be considered. The exportation of the P.2 variant, carrying the E484K mutation, deserves attention. One month after the first description of P.1 and P.2 importations from Brazil to Madrid, these variants were identified circulating in the community, in cases without a travel history, and involved in household transmissions CONCLUSION: Whole genome sequencing of SARS-CoV-2 positive travellers arriving from Brazil allowed us to identify the first importations of P.1 and P.2 variants to Spain and their early community transmission.


Assuntos
COVID-19 , SARS-CoV-2 , Brasil/epidemiologia , COVID-19/epidemiologia , Humanos , SARS-CoV-2/genética , Espanha/epidemiologia
11.
Am J Case Rep ; 23: e935115, 2022 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-35459759

RESUMO

BACKGROUND Dermoid cysts are rare benign intracranial tumors that usually present classic computed tomography (CT) and magnetic resonance imaging (MRI) characteristics, allowing for relatively simple diagnostic confirmation. Atypical imaging features can occur due to their diverse ectodermal-derived content, which can result in a diagnostic dilemma. Making an accurate diagnosis is essential for adequate management. CASE REPORT We present a case of a 39-year-old woman with past medical history of increased blood pressure, presenting with worsening headaches non-refractory to medication. Imaging revealed an extra-axial lesion within the midline posterior fossa with an occipital transdiploic linear channel. The lesion was T2 profoundly hypointense on brain MRI, and prominently hyperdense on non-contrast CT scan. Catheter angiography excluded vascular etiology. After complete lesion resection, results of the histopathologic examination were consistent with a dermoid cyst. Dermoid cysts that are hyperdense on CT and hypointense on T2-WI are extremely rare. CONCLUSIONS Complete surgical resection is the treatment of choice for most dermoid cysts. Atypical radiologic features, in an already rare intracranial tumor, can delay correct diagnosis and management. Recognition of these findings is therefore important for adequate imaging analysis of these lesions.


Assuntos
Neoplasias Encefálicas , Cisto Dermoide , Adulto , Encéfalo/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Cisto Dermoide/diagnóstico por imagem , Cisto Dermoide/cirurgia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X
12.
PLoS One ; 17(3): e0265309, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35320306

RESUMO

BACKGROUND: Adolescent sexual and reproductive health services in Chile have been primarily provided through health centers. Although some school-based initiatives have been implemented, to date, these have not been assessed. This study aims to identify strengths and challenges of the affectivity and sexuality component of the school-based 3A Program, a health program which seeks to prevent risk behaviors and promote healthy lifestyle habits within public schools (addressing health topics which in Spanish begin with the letter 'A', hence '3A'), implemented in the municipality of Lo Prado, city of Santiago. METHODS: We carried out a qualitative study with a descriptive-interpretative approach in three schools. We conducted in-depth interviews with students, teachers, health professionals, and school principals (N = 44); and focus groups with students (N = 3), teachers and health personnel (N = 3). The interviews were analyzed using thematic analysis. RESULTS: Participants highlight the integrative approach to health and to sexual and reproductive health promoted in the 3A Program, which is enhanced by the collaboration of interdisciplinary health teams. Permanent and expedited student access to sexual and reproductive health care is achieved, and affectional bonds are developed between students and the Program's health staff. The Program assists female participants to imagine and form identities that are not inherently tied to motherhood. It also assists boys and LGBTQ+ adolescents in feeling included as relevant actors in sexual and reproductive health and decision making. The delivery of contraception in schools is highly valued. The most significant challenge identified is ensuring effective and ongoing collaboration between health staff and teachers. CONCLUSION: Participants value the effectivity and sexuality component of the 3A Program as an initiative to improve adolescents' access to sexual and reproductive health care. Our findings suggest that this Program could be replicated throughout the region and the country to improve the quality and accessibility of health services for adolescents.


Assuntos
Saúde Reprodutiva , Saúde Sexual , Adolescente , Chile , Feminino , Humanos , Masculino , Instituições Acadêmicas , Comportamento Sexual , Saúde Sexual/educação
13.
Antioxidants (Basel) ; 11(2)2022 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-35204179

RESUMO

Glutathione is an important antioxidant that plays a crucial role in the cellular protection against oxidative stress and detoxification of electrophilic mutagens, and carcinogens. Glutathione transferases are enzymes catalyzing glutathione-dependent reactions that lead to inactivation and conjugation of toxic compounds, processes followed by subsequent excretion of the detoxified products. Degeneration and loss of neuromelanin-containing dopaminergic neurons in the nigrostriatal neurons generally involves oxidative stress, neuroinflammation, alpha-synuclein aggregation to neurotoxic oligomers, mitochondrial dysfunction, protein degradation dysfunction, and endoplasmic reticulum stress. However, it is still unclear what triggers these neurodegenerative processes. It has been reported that aminochrome may elicit all of these mechanisms and, interestingly, aminochrome is formed inside neuromelanin-containing dopaminergic neurons during neuromelanin synthesis. Aminochrome is a neurotoxic ortho-quinone formed in neuromelanin synthesis. However, it seems paradoxical that the neurotoxin aminochrome is generated during neuromelanin synthesis, even though healthy seniors have these neurons intact when they die. The explanation of this paradox is the existence of protective tools against aminochrome neurotoxicity composed of the enzymes DT-diaphorase, expressed in these neurons, and glutathione transferase M2-2, expressed in astrocytes. Recently, it has been reported that dopaminergic neurons can be protected by glutathione transferase M2-2 from astrocytes, which secrete exosomes containing the protective enzyme.

14.
Neural Regen Res ; 17(9): 1861-1866, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35142659

RESUMO

Astrocytes protect neurons by modulating neuronal function and survival. Astrocytes support neurons in several ways. They provide energy through the astrocyte-neuron lactate shuttle, protect neurons from excitotoxicity, and internalize neuronal lipid droplets to degrade fatty acids for neuronal metabolic and synaptic support, as well as by their high capacity for glutamate uptake and the conversion of glutamate to glutamine. A recent reported astrocyte system for protection of dopamine neurons against the neurotoxic products of dopamine, such as aminochrome and other o-quinones, were generated under neuromelanin synthesis by oxidizing dopamine catechol structure. Astrocytes secrete glutathione transferase M2-2 through exosomes that transport this enzyme into dopaminergic neurons to protect these neurons against aminochrome neurotoxicity. The role of this new astrocyte protective mechanism in Parkinson´s disease is discussed.

15.
Lancet Reg Health Am ; 6: 100117, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36777889

RESUMO

Background: Mortality rates among adults with candidemia vary widely in different geographical settings. Studies directly comparing epidemiology and clinical practices between countries are scarce and could bring insights into improving clinical outcomes. Methods: Retrospective cohort including adults with candidemia diagnosed in five tertiary hospitals from Brazil and Spain between 2010-2018. Adequate therapeutic management included appropriate antifungal therapy and central-venous-catheter (CVC) removal within 48 h of fungemia. Primary endpoints were mortality rates at 14 and 30 days. Secondary endpoints were prognostic factors associated with 30-day mortality. Findings: Overall, 720 patients were included, being 323 from Spain. Spanish patients received echinocandins more often (52·5% vs. 39·3%, p = 0.001), initiated antifungals earlier [2 (0-7) vs. 2 days (0-16), p<0.001], and had faster CVC-removal [1 (0-42) vs. 2 days (0-38), p = 0.012]. Mortality was higher among Brazilians at 14 days (35·8% vs. 20·1%, p<0.001), and at 30 days (51·9% vs. 31·6%, p < 0.001). Factors associated with mortality included: age [OR 1·02, 95%CI (1·008-1·032), p = 0·001], neutropenia [OR 3·24, 95%CI (1·594-6·585), p = 0·001], chronic pulmonary disease [OR 2·26, 95%CI (1·495-3·436), p < 0·001], corticosteroids [OR 1·45, 95%CI (1·018-2·079), p = 0·039], Pitt-Score>1 [OR 2·56, 95%CI (1·776-3·690), p < 0·001], and inadequate therapeutic management [OR 2·84, 95%CI (1·685-4·800), p < 0·001]. Being from Spain [OR 0·51, 95%CI (0·359-0·726), p < 0·001] and C. parapsilosis [OR 0·36, 95%CI (0·233-0·568), p < 0·001] were protective. Interpretation: Higher mortality rates were observed in Brazil. Factors associated with 30-day mortality included mainly epidemiological characteristics and inadequate therapeutic management. Thus, effective and prompt antifungals combined with CVC-removal still need to be emphasized in order to improve the prognosis of adults with candidemia. Funding: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2017/02203-7); CAPES Foundation (PDSE 88881.187981/2018-01).

16.
Enferm Infecc Microbiol Clin ; 40(5): 262-265, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34099945

RESUMO

Introduction: SARS-CoV-2variants of concern (VOC) have been described in the UK (B.1.1.7), South Africa (B.1.351) and Brazil (P.1). Among them, the most scarce information has been obtained from the P.1 variant and more data on its global presence and about its spreading dynamics are needed. Methods: Whole genome sequencing was performed prospectively on travellers arriving from Brazil and on a random selection of SARS-CoV-2 positive cases from our population. Results: In this study we report the first SARS-CoV-2 P.1 and P.2 variants exported from Brazil to Spain. The case infected with the P.1 variant, who had only stayed in Rio de Janeiro, required hospitalisation. The two P.2 cases remained asymptomatic. A wider distribution for P.1 variant beyond the Brazilian Amazonia should be considered. The exportation of the P.2 variant, carrying the E484K mutation, deserves attention. One month after the first description of P.1 and P.2 importations from Brazil to Madrid, these variants were identified circulating in the community, in cases without a travel history, and involved in household transmissions. Conclusion: Whole genome sequencing of SARS-CoV-2 positive travellers arriving from Brazil allowed us to identify the first importations of P.1 and P.2 variants to Spain and their early community transmission.


Introducción: Se han descrito «variantes de preocupación¼ (VOC) de SARS-CoV-2 en el Reino Unido (B.1.1.7), Sudáfrica (B.1.351) y Brasil (P.1). Entre ellas, se dispone de información más escasa para la variante P.1 y se necesitan más datos sobre su presencia global y sobre su dinámica de expansión. Métodos: Se realizó secuenciación del genoma completo de forma prospectiva de SARS-CoV-2 en viajeros procedentes de Brasil y en una selección aleatoria de casos positivos de SARS-CoV-2 de nuestra población. Resultados: En este estudio reportamos las primeras variantes de SARS-CoV-2 P.1 y P.2 exportadas desde Brasil a España. El caso infectado por la variante P.1, que solo había permanecido en Río de Janeiro, requirió hospitalización. Los 2 casos de la variante P.2 permanecieron asintomáticos. Se debe considerar una distribución más amplia para la variante P.1 más allá de la Amazonía brasileña. La exportación de la variante P.2, que porta la mutación E484K, merece asimismo atención adicional. Un mes después de la primera descripción de las importaciones de P.1 y P.2 de Brasil a Madrid, se identificaron estas variantes circulando en la comunidad, en casos sin antecedentes de viaje, e implicadas en transmisiones domiciliarias. Conclusión: La secuenciación de genoma completo de viajeros positivos para SARS-CoV-2 procedentes de Brasil nos permitió identificar las primeras importaciones de variantes P.1 y P.2 a España y su transmisión comunitaria precoz.

17.
Transbound Emerg Dis ; 69(2): 327-336, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33411991

RESUMO

Recurrent tuberculosis occurs due to exogenous reinfection or reactivation/persistence. We analysed 90 sequential MDR Mtb isolates obtained in Argentina from 27 patients with previously diagnosed MDR-TB that recurred in 2018 (1-10 years, 2-10 isolates per patient). Three long-term predominant strains were responsible for 63% of all MDR-TB recurrences. Most of the remaining patients were infected by strains different from each other. Reactivation/persistence of the same strain caused all but one recurrence, which was due to a reinfection with a predominant strain. One of the prevalent strains showed marked stability in the recurrences, while in another strain higher SNP-based diversity was observed. Comparisons of intra- versus inter-patient SNP distances identified two possible reinfections with closely related variants circulating in the community. Our results show a complex scenario of MDR-TB infections in settings with predominant MDR Mtb strains.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Animais , Argentina/epidemiologia , Mycobacterium tuberculosis/genética , Reinfecção/veterinária , Tuberculose/veterinária , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/veterinária
18.
Transbound Emerg Dis ; 69(3): 1065-1072, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-33687788

RESUMO

Costa Rica has a low incidence of tuberculosis. Thus, identifying transmission hotspots is key to implement interventions. A tuberculosis outbreak was suspected in a prison in Costa Rica. Given the suboptimal quality of the samples received in our laboratory in Madrid, we applied alternative schemes for their analysis. In the first scheme, we bypassed the standard approach of applying systematic mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) and used a strain-specific polymerase chain reaction (PCR) that allowed identifying a cluster involving six cases (C1). The second scheme followed the canonical MIRU-VNTR path coupled with a whole-genomic amplification step, by which a second unsuspected overlapping cluster (C2), was detected in the same prison. These findings justified the implementation of a surveillance programme adapted to local resources based on a tailored multiplex allele-specific oligonucleotide (ASO)-PCR targeting C1 and C2. Presence of the C2 strain at a different prison was determined. ASO-PCR was applied extensively and alerted to the active circulation of one of the strains within and beyond prisons. Our study shows that alternative methodological strategies may provide useful data in settings with lack of resources for performing systematic standard molecular epidemiology programmes and/or with suboptimal material for analysis.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Animais , Costa Rica/epidemiologia , Surtos de Doenças/veterinária , Genótipo , Repetições Minissatélites , Mycobacterium tuberculosis/genética , Prisões , Tuberculose/epidemiologia , Tuberculose/microbiologia , Tuberculose/veterinária
19.
Genes (Basel) ; 12(8)2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34440318

RESUMO

The target of rapamycin (TOR), also known as FKBP-rapamycin associated protein (FRAP), is a protein kinase belonging to the PIKK (phosphatidylinositol 3-kinase (PI3K)-related kinases) family. TOR kinases are involved in several signaling pathways that control cell growth and proliferation. Entamoeba histolytica, the protozoan parasite that causes human amoebiasis, contains two genes encoding TOR-like proteins: EhFRAP and EhTOR2. To assess their potential as drug targets to control the cell proliferation of E. histolytica, we studied the structural features of EhFRAP and EhTOR2 using a biocomputational approach. The overall results confirmed that both TOR amoebic homologs share structural similarities with functional TOR kinases, and show inherent abilities to form TORC complexes and participate in protein-protein interaction networks. To our knowledge, this study represents the first in silico characterization of the structure-function relationships of EhFRAP and EhTOR2.


Assuntos
Biologia Computacional/métodos , Entamoeba histolytica/metabolismo , Proteínas de Protozoários/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Sequência de Aminoácidos , Conformação Proteica , Mapas de Interação de Proteínas , Proteínas de Protozoários/química , Alinhamento de Sequência , Serina-Treonina Quinases TOR/química
20.
Antibiotics (Basel) ; 10(7)2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34356728

RESUMO

Globally, tuberculosis (TB) remains a prevalent threat to public health. In 2019, TB affected 10 million people and caused 1.4 million deaths. The major challenge for controlling this infectious disease is the emergence and spread of drug-resistant Mycobacterium tuberculosis, the causative agent of TB. The antibiotic streptomycin is not a current first-line anti-TB drug. However, WHO recommends its use in patients infected with a streptomycin-sensitive strain. Several mutations in the M. tuberculosisrpsL, rrs and gidB genes have proved association with streptomycin resistance. In this study, we performed a molecular analysis of these genes in clinical isolates to determine the prevalence of known or novel mutations. Here, we describe the genetic analysis outcome. Furthermore, a biocomputational analysis of the MtGidB L101F variant, the product of a novel mutation detected in gidB during molecular analysis, is also reported as a theoretical approach to study the apparent genotype-phenotype association.

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