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1.
J Virol ; 96(3): e0114021, 2022 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-34851149

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) has evolved to escape the immune surveillance for a survival advantage leading to a strong modulation of host's immune responses and favoring secondary bacterial infections. However, limited data are available on how the immunological and transcriptional responses elicited by virulent and low-virulent PRRSV-1 strains are comparable and how they are conserved during the infection. To explore the kinetic transcriptional signature associated with the modulation of host immune response at lung level, a time-series transcriptomic analysis was performed in bronchoalveolar lavage cells upon experimental in vivo infection with two PRRSV-1 strains of different virulence, virulent subtype 3 Lena strain or the low-virulent subtype 1 3249 strain. The time-series analysis revealed overlapping patterns of dysregulated genes enriched in T-cell signaling pathways among both virulent and low-virulent strains, highlighting an upregulation of co-stimulatory and co-inhibitory immune checkpoints that were disclosed as Hub genes. On the other hand, virulent Lena infection induced an early and more marked "negative regulation of immune system process" with an overexpression of co-inhibitory receptors genes related to T-cell and NK cell functions, in association with more severe lung lesion, lung viral load, and BAL cell kinetics. These results underline a complex network of molecular mechanisms governing PRRSV-1 immunopathogenesis at lung level, revealing a pivotal role of co-inhibitory and co-stimulatory immune checkpoints in the pulmonary disease, which may have an impact on T-cell activation and related pathways. These immune checkpoints, together with the regulation of cytokine-signaling pathways, modulated in a virulence-dependent fashion, orchestrate an interplay among pro- and anti-inflammatory responses. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the major threats to swine health and global production, causing substantial economic losses. We explore the mechanisms involved in the modulation of host immune response at lung level performing a time-series transcriptomic analysis upon experimental infection with two PRRSV-1 strains of different virulence. A complex network of molecular mechanisms was revealed to control the immunopathogenesis of PRRSV-1 infection, highlighting an interplay among pro- and anti-inflammatory responses as a potential mechanism to restrict inflammation-induced lung injury. Moreover, a pivotal role of co-inhibitory and co-stimulatory immune checkpoints was evidenced, which may lead to progressive dysfunction of T cells, impairing viral clearance and leading to persistent infection, favoring as well secondary bacterial infections or viral rebound. However, further studies should be conducted to evaluate the functional role of immune checkpoints in advanced stages of PRRSV infection and explore a possible T-cell exhaustion state.


Assuntos
Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno , Síndrome Respiratória e Reprodutiva Suína/genética , Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/fisiologia , Transcriptoma , Animais , Biópsia , Lavagem Broncoalveolar , Biologia Computacional/métodos , Ontologia Genética , Redes Reguladoras de Genes , Interações Hospedeiro-Patógeno/genética , Contagem de Leucócitos , Síndrome Respiratória e Reprodutiva Suína/diagnóstico , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Suínos , Avaliação de Sintomas , Carga Viral , Virulência
2.
Osteoarthritis Cartilage ; 31(7): 919-933, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36893980

RESUMO

OBJECTIVE: Defects in autophagy contribute to joint aging and Osteoarthritis (OA). Identifying specific autophagy types could be useful for developing novel treatments for OA. DESIGN: An autophagy-related gene array was performed in blood from non-OA and knee OA subjects from the Prospective Cohort of A Coruña (PROCOAC). The differential expression of candidate genes was confirmed in blood and knee cartilage and a regression analysis was performed adjusting for age and BMI. HSP90A, a chaperone mediated autophagy (CMA) marker was validated in human knee joint tissues, as well as, in mice with aging-related and surgically-induced OA. The consequences of HSP90AA1 deficiency were evaluated on OA pathogenesis. Finally, the contribution of CMA to homeostasis was studied by assessing the capacity to restore proteostasis upon ATG5-mediated macroautophagy deficiency and genetic HSP90AA1 overexpression. RESULTS: 16 autophagy-related genes were significantly down-regulated in blood from knee OA subjects. Validation studies showed that HSP90AA1 was down-regulated in blood and human OA cartilage and correlated with risk incidence of OA. Moreover, HSP90A was reduced in human OA joints tissues and with aging and OA in mice. HSP90AA1 knockdown was linked to defective macroautophagy, inflammation, oxidative stress, senescence and apoptosis. However, macroautophagy deficiency increased CMA, highlighting the CMA-macroautophagy crosstalk. Remarkably, CMA activation was sufficient to protect chondrocytes from damage. CONCLUSIONS: We show that HSP90A is a key chaperone for chondrocyte homeostasis, while defective CMA contributes to joint damage. We propose that CMA deficiency is a relevant disease mechanism and could represent a therapeutic target for OA.


Assuntos
Cartilagem Articular , Autofagia Mediada por Chaperonas , Osteoartrite do Joelho , Humanos , Camundongos , Animais , Osteoartrite do Joelho/patologia , Estudos Prospectivos , Cartilagem Articular/patologia , Envelhecimento/genética , Articulação do Joelho/patologia , Autofagia/genética , Condrócitos/metabolismo
3.
Chemistry ; 29(60): e202301845, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37540499

RESUMO

The pharmacological activity of organotin(IV) complexes in cancer therapy is well recognized but their large applicability is hampered by their poor water solubility. Hence, carbon dots, in particular nitrogen-doped graphene quantum dots (NGQDs), may be a promising alternative for the efficient delivery of organotin(IV) compounds as they have a substantial aqueous solubility, a good chemical stability, and non-toxicity as well as a bright photoluminescence that make them ideal for theranostic applications against cancer. Two different multifunctional nanosystems have been synthesized and fully characterized based on two fragments of organotin-based cytotoxic compounds and 4-formylbenzoic acid (FBA), covalently grafted onto the NGQDs surface. Subsequently, an in vitro determination of the therapeutic and theranostic potential of the achieved multifunctional systems was carried out. The results showed a high cytotoxic potential of the NGQDs-FBA-Sn materials against breast cancer cell line (MDA-MB-231) and a lower effect on a non-cancer cell line (kidney cells, HEK293T). Besides, thanks to their optical properties, the dots enabled their fluorescence molecular imaging in the cytoplasmatic region of the cells pointing towards a successful cellular uptake and a release of the metallodrug inside cancer cells (NGQDs-FBA-Sn).


Assuntos
Grafite , Pontos Quânticos , Neoplasias de Mama Triplo Negativas , Humanos , Grafite/química , Pontos Quânticos/química , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Células HEK293 , Imagem Molecular
4.
BMC Infect Dis ; 23(1): 847, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38041069

RESUMO

Research has shown that multidimensional approaches to Chagas disease (CD), integrating its biomedical and psycho-socio-cultural components, are successful in enhancing early access to diagnosis, treatment and sustainable follow-up.For the first time, a consulate was selected for a community-based CD detection campaign. Two different strategies were designed, implemented and compared between 2021 and 2022 at the Consulate General of Bolivia and a reference health facility in Barcelona open to all Bolivians in Catalonia.Strategy 1 consisted in CD awareness-raising activities before referring those interested to the reference facility for infectious disease screening. Strategy 2 offered additional in-situ serological CD screening. Most of the 307 participants were Bolivian women residents in Barcelona. In strategy 1, 73 people (35.8% of those who were offered the test) were screened and 19.2% of them were diagnosed with CD. Additionally, 53,4% completed their vaccination schedules and 28.8% were treated for other parasitic infections (strongyloidiasis, giardiasis, eosinophilia, syphilis). In strategy 2, 103 people were screened in-situ (100% of those who were offered the test) and 13.5% received a CD diagnosis. 21,4% completed their vaccination schedule at the reference health facility and 2,9% were referred for iron deficiency anemia, strongyloidiasis or chronic hepatitis C.The fact that the screening took place in an official workplace of representatives of their own country, together with the presence of community-based participants fueled trust and increased CD understanding. Each of the strategies assessed had different benefits. Opportunities for systematic integration for CD based on community action in consulates may enhance early access to diagnosis, care and disease prevention.


Assuntos
Doença de Chagas , Eosinofilia , Estrongiloidíase , Humanos , Feminino , Doença de Chagas/diagnóstico , Doença de Chagas/epidemiologia , Programas de Rastreamento , Participação da Comunidade
5.
Osteoporos Int ; 33(5): 1177-1180, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34741636

RESUMO

Snyder-Robinson syndrome is an extremely rare genetic disorder, caused by mutations of the spermine synthase gene. We report a novel case of Snyder-Robinson syndrome, caused by a de novo mutation and first misdiagnosed with osteogenesis imperfecta. Clinical features, course, and genetic analysis are presented. The patient was treated with bisphosphonates for a decade, until developing an atypical femoral fracture. Teriparatide was then administered for 2 years and then changed to denosumab every 6 months, improving his bone density mass and preventing further fractures.


Assuntos
Deficiência Intelectual Ligada ao Cromossomo X , Osteogênese Imperfeita , Espermina Sintase , Diagnóstico Diferencial , Humanos , Deficiência Intelectual Ligada ao Cromossomo X/diagnóstico , Deficiência Intelectual Ligada ao Cromossomo X/genética , Osteogênese Imperfeita/diagnóstico , Osteogênese Imperfeita/tratamento farmacológico , Osteogênese Imperfeita/genética , Espermina Sintase/genética
6.
Liver Int ; 42(8): 1751-1761, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35635535

RESUMO

BACKGROUND AND AIMS: Pakistani migrants in Catalonia, Spain, could have high hepatitis C virus (HCV) prevalence. The aims of the HepClink study were (i) to implement and assess the quality of a micro-elimination strategy based on a community intervention and (ii) to obtain data from primary care (PC) registries as a baseline comparator. METHODS: The community intervention targeted Pakistani adults and consisted of education, screening and simplified access to treatment. Quality indicators were calculated (effectiveness, impact and acceptability). The testing rate, the prevalence of HCV antibodies and HCV-RNA were compared with those observed in the Pakistani population accessing PC in the previous year. RESULTS: A total of 505 participants were recruited through the community intervention (64.6% men, median 37 years) vs those accessing PC (N = 25 455, 70.9% men, median 38 years). Among study participants, 35.1% did not know about HCV and 9.7% had been previously tested. The testing rate in the community intervention was 99.4% vs 50.7% in PC. Prevalence was 4.6% vs 7.1% (p = .008) for HCV antibodies and 1.4% (3/6 new diagnoses) vs 2.4% (p = .183) for HCV-RNA. Among the six viremic patients, three began treatment within the intervention and two through the usual circuit and all completed the full course. CONCLUSIONS: This novel community intervention was well accepted and effective at reaching a Pakistani migrant population with a low-level knowledge of HCV and largely not tested before. The observed prevalence and the high unawareness of their HCV status justify a targeted screening in this group both in the community and in PC.


Assuntos
Hepatite C , Migrantes , Adulto , Feminino , Hepacivirus/genética , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Hepatite C/prevenção & controle , Anticorpos Anti-Hepatite C , Humanos , Masculino , Paquistão/epidemiologia , Prevalência , RNA , Espanha/epidemiologia
7.
BMC Infect Dis ; 22(1): 298, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35346096

RESUMO

BACKGROUND: As a Neglected Tropical Disease associated with Latin America, Chagas Disease (CD) is little known in non-endemic territories of the Americas, Europe and Western Pacific, making its control challenging, with limited detection rates, healthcare access and consequent epidemiological silence. This is reinforced by its biomedical characteristics-it is usually asymptomatic-and the fact that it mostly affects people with low social and financial resources. Because CD is mainly a chronic infection, which principally causes a cardiomyopathy and can also cause a prothrombotic status, it increases the risk of contracting severe COVID-19. METHODS: In order to get an accurate picture of CD and COVID-19 overlapping and co-infection, this operational research draws on community-based experience and participative-action-research components. It was conducted during the Bolivian elections in Barcelona on a representative sample of that community. RESULTS: The results show that 55% of the people interviewed had already undergone a previous T. cruzi infection screening-among which 81% were diagnosed in Catalonia and 19% in Bolivia. The prevalence of T. cruzi infection was 18.3% (with 3.3% of discordant results), the SARS-CoV-2 22.3% and the coinfection rate, 6%. The benefits of an integrated approach for COVID-19 and CD were shown, since it only took an average of 25% of additional time per patient and undoubtedly empowered the patients about the co-infection, its detection and care. Finally, the rapid diagnostic test used for COVID-19 showed a sensitivity of 89.5%. CONCLUSIONS: This research addresses CD and its co-infection, through an innovative way, an opportunity of systematic integration, during the COVID-19 pandemic.


Assuntos
COVID-19 , Doença de Chagas , Bolívia/epidemiologia , COVID-19/epidemiologia , Doença de Chagas/diagnóstico , Doença de Chagas/epidemiologia , Humanos , Pandemias , SARS-CoV-2
8.
Mem Inst Oswaldo Cruz ; 117: e200460, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35674539

RESUMO

Chagas is a complex, multidimensional phenomenon in which political, economic, environmental, biomedical, epidemiological, psychological, and sociocultural factors intersect. Nonetheless, the hegemonic conceptualisation has long envisioned Chagas as primarily a biomedical question, while ignoring or downplaying the other dimensions, and this limited view has reinforced the disease's long neglect. Integrating the multiple dimensions of the problem into a coherent approach adapted to field realities and needs represents an immense challenge, but the payoff is more effective and sustainable experiences, with higher social awareness, increased case detection and follow-up, improved adherence to care, and integrated participation of various actors from multiple action levels. Information, Education, and Communication (IEC) initiatives have great potential for impact in the implementation of multidimensional programs of prevention and control successfully customised to the diverse and complex contexts where Chagas disease persists.


Assuntos
Doença de Chagas , Compreensão , Doença de Chagas/prevenção & controle , Comunicação , Humanos
9.
Mem Inst Oswaldo Cruz ; 117: e220066, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35858002

RESUMO

It is well documented that Chagas disease (CD) can pose a public health problem to countries. As one of the World Health Organization Neglected Tropical Diseases undoubtedly calls for comprehensive healthcare, transcending a restricted biomedical approach. After more than a century since their discovery, in 1909, people affected by CD are still frequently marginalised and/or neglected. The aim of this article is to tell the story of their activism, highlighting key historical experiences and successful initiatives, from 1909 to 2019. The first association was created in 1987, in the city of Recife, Brazil. So far, thirty associations have been reported on five continents. They were created as independent non-profit civil society organisations and run democratically by affected people. Among the common associations' objectives, we notably find: increase the visibility of the affected; make their voice heard; build bridges between patients, health system professionals, public health officials, policy makers and the academic and scientific communities. The International Federation of Associations of People Affected by CD - FINDECHAGAS, created in 2010 with the input of the Americas, Europe and the Western Pacific, counts as one of the main responses to the globalisation of CD. Despite all the obstacles and difficulties encountered, the Federation has thrived, grown, and matured. As a result of this mobilisation along with the support of many national and international partners, in May 2019 the 72nd World Health Assembly decided to establish World Chagas Disease Day, on 14 April. The associative movement has increased the understanding of the challenges related to the disease and breaks the silence around Chagas disease, improving surveillance, and sustaining engagement towards the United Nations 2030 agenda.


Assuntos
Doença de Chagas , Saúde Global , Aniversários e Eventos Especiais , Doença de Chagas/epidemiologia , Doença de Chagas/história , Doença de Chagas/prevenção & controle , Saúde Global/história , Saúde Global/estatística & dados numéricos , História do Século XX , História do Século XXI , Humanos , Organização Mundial da Saúde
10.
Med Intensiva ; 2022 Sep 26.
Artigo em Espanhol | MEDLINE | ID: mdl-36187363

RESUMO

OBJECTIVES: incidence of post-intensive care syndrome at one month after hospital discharge in surviving critically ill COVID 19 patients and to identify associated factors. DESIGN: prospective cohort study. SETTING: two multipurpose critical care units of the Araba University Hospital.Patients admitted to critical care units for severe acute respiratory failure secondary to COVID 19. INTERVENTION: none. VARIABLES OF INTEREST: demographic variables, length of stay, Charlson index, APACHE II, SOFA, days of mechanical ventilation, tracheotomy, delirium, tetraparesis of the critical patient, EuroQol 5D5L, Minimental Test. RESULTS: a deterioration in the EuroQol health index (HI) from 90.9 ± 16.9 to 70.9 ± 24.7 (p < 0.001) was observed. The impairment of the five EuroQol domains is: mobility (46.1%), usual activities (44.7%), discomfort/pain (30.7%), psychological domain (27.3%) and self-care (20.3%). The 61.5% suffer a significant decrease in their health index. Multivariate analysis by logistic regression shows us that delirium (OR= 3.01; 95%CI: 1.01-8.9; p= 0.047) and tracheostomy (OR= 2.37; 95%CI: 1.09-5.14; p= 0.029) show association with drop in EuroQoL 5D5L SI. The area under the ROC curve of the model is 67.3%, with a confidence interval between 58% and 76%. The model is calibrated using the Hosmer-Lemeshow test:(χ2=0.468; p=0.792). Only 1.2% of patients showed a score ≤ 24, clearly pathological, on the Folstein's Minimental Test. CONCLUSIONS: delirium and need for tracheostomy are associated with post-intensive care syndrome assessed by EuroQol 5D5L.

11.
Chemistry ; 27(9): 2993-2996, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33231902

RESUMO

The combination of 2D materials opens a wide range of possibilities to create new-generation structures with multiple applications. Covalently cross-linked approaches are a ground-breaking strategy for the formation of homo or heterostructures made by design. However, the covalent assembly of transition metal dichalcogenides flakes is relatively underexplored. Here, a simple covalent cross-linking method to build 2H-MoS2 -MoS2 homostructures is described, using commercially available bismaleimides. These assemblies are mainly connected vertically, basal plane to basal plane, creating specific molecular sized spaces between MoS2 sheets. Therefore, this straightforward approach gives access to the controlled connection of sulfide-based 2D materials.

12.
Ultrasound Obstet Gynecol ; 58(5): 669-676, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34358386

RESUMO

OBJECTIVE: To evaluate the accuracy of transvaginal sonography (TVS) for detecting parametrial deep endometriosis, using laparoscopy as the reference standard. METHODS: A search was performed in PubMed/MEDLINE and Web of Science for studies evaluating TVS for detecting parametrial involvement in women with suspected deep endometriosis, as compared with laparoscopy, from January 2000 to December 2020. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to evaluate the quality of the studies. Pooled sensitivity, specificity and positive and negative likelihood ratios for TVS in the detection of parametrial deep endometriosis were calculated, and the post-test probability of parametrial deep endometriosis following a positive or negative test was determined. RESULTS: The search identified 134 citations. Four studies, comprising 560 patients, were included in the analysis. The mean prevalence of parametrial deep endometriosis at surgery was 18%. Overall, the pooled estimated sensitivity, specificity and positive and negative likelihood ratios of TVS in the detection of parametrial deep endometriosis were 31% (95% CI, 10-64%), 98% (95% CI, 95-99%), 18.5 (95% CI, 8.8-38.9) and 0.70 (95% CI, 0.46-1.06), respectively. The diagnostic odds ratio was 26 (95% CI, 10-68). Heterogeneity was high. Visualization of a lesion suspected to be parametrial deep endometriosis on TVS increased significantly the post-test probability of parametrial deep endometriosis. CONCLUSION: TVS has high specificity but low sensitivity for the detection of parametrial deep endometriosis. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Assuntos
Endometriose/diagnóstico por imagem , Peritônio/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Feminino , Humanos , Valor Preditivo dos Testes , Prevalência , Sensibilidade e Especificidade , Vagina/diagnóstico por imagem
13.
Artigo em Inglês | MEDLINE | ID: mdl-32015035

RESUMO

We aimed to assess the rate and predictive factors of bloodstream infection (BSI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa in neutropenic cancer patients. We performed a multicenter, retrospective cohort study including oncohematological neutropenic patients with BSI due to P. aeruginosa conducted across 34 centers in 12 countries from January 2006 to May 2018. A mixed logistic regression model was used to estimate a model to predict the multidrug resistance of the causative pathogens. Of a total of 1,217 episodes of BSI due to P. aeruginosa, 309 episodes (25.4%) were caused by MDR strains. The rate of multidrug resistance increased significantly over the study period (P = 0.033). Predictors of MDR P. aeruginosa BSI were prior therapy with piperacillin-tazobactam (odds ratio [OR], 3.48; 95% confidence interval [CI], 2.29 to 5.30), prior antipseudomonal carbapenem use (OR, 2.53; 95% CI, 1.65 to 3.87), fluoroquinolone prophylaxis (OR, 2.99; 95% CI, 1.92 to 4.64), underlying hematological disease (OR, 2.09; 95% CI, 1.26 to 3.44), and the presence of a urinary catheter (OR, 2.54; 95% CI, 1.65 to 3.91), whereas older age (OR, 0.98; 95% CI, 0.97 to 0.99) was found to be protective. Our prediction model achieves good discrimination and calibration, thereby identifying neutropenic patients at higher risk of BSI due to MDR P. aeruginosa The application of this model using a web-based calculator may be a simple strategy to identify high-risk patients who may benefit from the early administration of broad-spectrum antibiotic coverage against MDR strains according to the local susceptibility patterns, thus avoiding the use of broad-spectrum antibiotics in patients at a low risk of resistance development.


Assuntos
Bacteriemia/microbiologia , Farmacorresistência Bacteriana Múltipla , Neoplasias/microbiologia , Neutropenia/microbiologia , Infecções por Pseudomonas/microbiologia , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Modelos Biológicos , Neoplasias/complicações , Neutropenia/complicações , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
14.
Chemistry ; 26(29): 6629-6634, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32101348

RESUMO

Most air-stable 2D materials are relatively inert, which makes their chemical modification difficult. In particular, in the case of MoS2 , the semiconducting 2 H-MoS2 is much less reactive than its metallic counterpart, 1T-MoS2 . As a consequence, there are hardly any reliable methods for the covalent modification of 2 H-MoS2 . An ideal method for the chemical functionalization of such materials should be both mild, not requiring the introduction of a large number of defects, and versatile, allowing for the decoration with as many different functional groups as possible. Herein, a comprehensive study on the covalent functionalization of 2 H-MoS2 with maleimides is presented. The use of a base (Et3 N) leads to the in situ formation of a succinimide polymer layer, covalently connected to MoS2 . In contrast, in the absence of base, functionalization stops at the molecular level. Moreover, the functionalization protocol is mild (occurs at room temperature), fast (nearly complete in 1 h), and very flexible (11 different solvents and 10 different maleimides tested). In practical terms, the procedures described here allow for the chemist to manipulate 2 H-MoS2 in a very flexible way, decorating it with polymers or molecules, and with a wide range of functional groups for subsequent modification. Conceptually, the spurious formation of an organic polymer might be general to other methods of functionalization of 2D materials, where a large excess of molecular reagents is typically used.

15.
Mov Disord ; 35(2): 316-325, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31710401

RESUMO

BACKGROUND: Impulse control disorders related to alterations in the mesocorticolimbic dopamine network occur in Parkinson's disease (PD). Our objective was to investigate the functional neural substrates of reward processing and inhibitory control in these patients. METHODS: Eighteen PD patients with impulse control disorders, 17 without this complication, and 18 healthy controls performed a version of the Iowa Gambling Task during functional magnetic resonance scanning under 3 conditions: positive, negative, and mixed feedback. Whole-brain contrasts, regions of interest, time courses, functional connectivity analyses, and brain-behavior associations were examined. RESULTS: PD patients with impulse control disorders exhibited hyperactivation in subcortical and cortical regions typically associated with reward processing and inhibitory control compared with their PD and healthy control counterparts. Time-course analyses revealed that only PD patients with impulse control disorders exhibited stronger signal intensity during the initial versus final periods of the negative-feedback condition in bilateral insula, and right ventral striatum. Interestingly, hyperactivation of all the examined right-lateralized frontostriatal areas during negative feedback was positively associated with impulse control disorder severity. Importantly, positive associations between impulse control disorder severity and regional activations in the right insula and right inferior frontal gyrus, but not the right subthalamic nucleus, were mediated by functional connectivity with the right ventral striatum. CONCLUSIONS: During a reward-based task, PD patients with impulse control disorders showed hyperactivation in a right-lateralized network of regions including the subthalamic nucleus that was strongly associated with impulse control disorder severity. In these patients, the right ventral striatum in particular played a critical role in modulating the functional dynamics of right-lateralized inhibitory-control frontal regions when facing penalties. © 2019 International Parkinson and Movement Disorder Society.


Assuntos
Encéfalo/fisiopatologia , Transtornos Disruptivos, de Controle do Impulso e da Conduta/psicologia , Inibição Neural/fisiologia , Doença de Parkinson/psicologia , Adulto , Idoso , Transtornos Disruptivos, de Controle do Impulso e da Conduta/etiologia , Feminino , Jogo de Azar/complicações , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson/complicações , Recompensa
16.
Eur J Nucl Med Mol Imaging ; 46(10): 2065-2076, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31273436

RESUMO

PURPOSE: Previous studies in patients with Parkinson's disease (PD) and impulse control disorders (ICDs) have produced heterogeneous results regarding striatal dopamine transporter (DaT) binding and activity in the mesocorticolimbic network. Our aim here was to study the relationship between striatal DaT availability and cortical metabolism, as well as motor, behavioural and cognitive features of PD patients with ICD. METHODS: In a group of PD patients with ICD (PD-ICD, n = 16) and 16 matched PD patients without ICD (PD-noICD, n = 16), DaT single-photon emission computed tomography (SPECT) imaging (DaTSCAN) was used to study DaT availability in predefined striatal volumes of interest (VOIs): putamen, caudate nucleus and ventral striatum (VS). In addition, the specific association of striatal DaT binding with cortical limbic and associative metabolic activity was evaluated by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in PD-ICD patients and investigated using statistical parametric mapping (SPM8). Finally, associations between DaT availability and motor, behavioural and cognitive features were assessed. RESULTS: PD-ICD patients had a significantly lower DaT density in the VS than PD-noICD patients, which was inversely associated with ICD severity. Lower DaT availability in the VS was associated with lower FDG uptake in several cortical areas belonging to the limbic and associative circuits, and in other regions involved in reward and inhibition processes (p < 0.0001 uncorrected; k > 50 voxels). No significant results were observed using a higher conservative threshold (p < 0.05; FDR corrected). PD-ICD patients also displayed impairment in interference and attentional Stroop Task execution, and more anxiety, all associated with reduced DaT availability in the VS and caudate nucleus. CONCLUSIONS: ICDs in PD patients are related to reduced DaT binding in the VS, which accounts for dysfunction in a complex cortico-subcortical network that involves areas of the mesolimbic and mesocortical systems, being associated with reward evaluation, salience attribution and inhibitory control processes.


Assuntos
Corpo Estriado/diagnóstico por imagem , Transtornos Disruptivos, de Controle do Impulso e da Conduta/diagnóstico por imagem , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Doença de Parkinson/diagnóstico por imagem , Substância Negra/diagnóstico por imagem , Idoso , Corpo Estriado/metabolismo , Transtornos Disruptivos, de Controle do Impulso e da Conduta/complicações , Transtornos Disruptivos, de Controle do Impulso e da Conduta/metabolismo , Transtornos Disruptivos, de Controle do Impulso e da Conduta/patologia , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Substância Negra/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único
17.
J Community Health ; 44(4): 704-711, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31222620

RESUMO

Chagas disease (CHD) has become a challenge in Spain due to the high prevalence of immigrants coming from endemic areas. One of the main difficulties for its control and elimination is its underdiagnosis. The identification and integral treatment of CHD are key to increasing rates of diagnosis, overcoming psycho-social barriers and avoiding CHD progression. Community interventions with in situ screening have proven to be a useful tool in detecting CHD among those with difficulties accessing health services. To determine the underdiagnosis rate of the population most susceptible to CHD among those attending two different Bolivian cultural events celebrated in Barcelona; to describe the sociodemographic characteristics of the people screened; and to analyse the results of the screening. The community interventions were carried out at two Bolivian cultural events held in Barcelona in 2017. Participants were recruited through community health agents. A questionnaire was given to determine the participants' prior knowledge of CHD. In situ screening was offered to those who had not previously been screened. Those who did not wish to be screened were asked for the reason behind their decision. Results were gathered in a database and statistical analyses were performed using STATA v14. 635 interviews were carried out. 95% of the subjects reported prior knowledge of CHD. 271 subjects were screened: 71.2% women and 28.8% men, of whom 87.8% were of Bolivian origin. The prevalence of CHD was 8.9%. Community health interventions with in situ screening are essential to facilitating access to diagnosis.


Assuntos
Doença de Chagas , Bolívia/etnologia , Doença de Chagas/diagnóstico , Doença de Chagas/epidemiologia , Doença de Chagas/etnologia , Serviços de Saúde Comunitária , Emigrantes e Imigrantes , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Programas de Rastreamento , Prevalência , Espanha
18.
Health Promot Int ; 34(Supplement_1): i82-i91, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30690456

RESUMO

With the objective of providing an insightful analysis of Chagas disease in the world, the authors share their collective reflections about the current situation of this public health problem in: rural environments of Latin America; urban environments of endemic and non-endemic areas everywhere; and, at a global level. A perspective based on the 'Democracy and Health Promotion' axis allowed the development of an innovative update about Chagas disease as a model of a complex socio-environmental health problem, with a key set of elements that goes beyond biomedical aspects. The authors created a dialogue between the fundamental elements of the Curitiba Statement on Health Promotion and Equity and crucial aspects of a reflection on the reality of Chagas disease today that at the same time challenges the different actors involved. With that reference, the call to promote a 'critical analysis of viabilities and opportunities for action, considering the potentialities and barriers imposed by the complexity of social movements in the present context of recedes and the loss of rights' was emphasized repeatedly. Finally, on the occasion of the recent creation of the Technical Group on Information, Education and Communication to control Chagas disease, WHO Department of Control of Neglected Tropical Diseases, the authors share reflections to propose an inclusive and transformative approach of health promotion-what we hope is a new horizon for people affected, directly and indirectly, by Chagas disease.


Assuntos
Doença de Chagas/prevenção & controle , Promoção da Saúde/organização & administração , Feminino , Promoção da Saúde/métodos , Direitos Humanos , Humanos , Masculino , Doenças Negligenciadas/prevenção & controle , Política , Fatores Socioeconômicos , Trypanosoma cruzi
19.
J Environ Manage ; 249: 109381, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31419670

RESUMO

It is presented an alternative biological method based on biomineralization mechanisms of Magnetotactic Bacteria (MTB) for the removal in groundwater, of soluble elements such as Fe+2and Mn+2. In first place, it was compared the effectiveness of MTB retention methods for obtention of concentrated volumes in microorganisms, then, it was carried out an inoculation process in groundwater samples and evaluate the removal rate of Fe+2 and Mn+2 in constant conditions of pH and temperature. It was identified electromagnetic method is more efficient in MTB retention, and that the inoculation processes of an enriched solution with MTB in groundwater samples allow to get average removal rates of 47.86% for Fe+2 and 15.26% for Mn+2. In addition, it was evaluated the removal rate of other metals due to magnetic properties of biominerals inside of MTB magnetosome. The highest removal in all cases occurred between the interval of 3 and 5 min of interaction and tended to stabilize in time.


Assuntos
Água Subterrânea , Magnetossomos , Bactérias Aeróbias , Ferro , Manganês
20.
J Inherit Metab Dis ; 41(6): 1037-1042, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29594644

RESUMO

INTRODUCTION: McArdle disease is an inborn disorder of muscle glycogen metabolism that produces exercise intolerance, and has been recently associated with low values ​​of lean mass (LM) and bone mineral content (BMC) and density (BMD) in affected adults. Here we aimed to study whether this bone health problem begins in childhood. METHODS: Forty children and adolescents were evaluated: 10 McArdle disease and 30 control children (mean age of both groups, 13 ± 2y). Body composition was evaluated by dual-energy X-ray absorptiometry and creatine kinase (CK) levels were determined in the patients as an estimate of muscle damage. RESULTS: Legs bone mass was significantly lower in patients than in controls (-36% for BMC and -22% for BMD). Moreover, patients had significantly higher LM values in the legs than controls, whereas no difference was found for fat mass. CK levels were positively associated with LM in McArdle patients. A correlation was found between LM and BMD variables in the control group but not in McArdle patients. CONCLUSION: We have identified a 'non-osteogenic muscle hypertrophy' in children with McArdle disease. This phenomenon warrants special attention since low osteogenesis at an early age predicts a high risk for osteoporosis later in life.


Assuntos
Composição Corporal , Densidade Óssea , Creatina Quinase/metabolismo , Doença de Depósito de Glicogênio Tipo V/metabolismo , Músculo Esquelético/patologia , Absorciometria de Fóton , Adolescente , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Estudos Transversais , Feminino , Doença de Depósito de Glicogênio Tipo V/complicações , Humanos , Hipertrofia/patologia , Perna (Membro)/fisiologia , Masculino , Osteoporose/etiologia , Osteoporose/patologia
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