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1.
Curr Opin Pulm Med ; 30(3): 243-251, 2024 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-38323419

RESUMO

PURPOSE OF REVIEW: The recent COVID-19 pandemic has shaped the epidemiology of other infectious diseases globally. International tourist arrivals are increasing and recovering to prepandemic levels. This review focuses on respiratory infections in travelers, highlighting the characteristics of the main imported viral, bacterial, fungal, and parasitic infections with pulmonary involvement. RECENT FINDINGS: A recent systematic review estimated a prevalence of respiratory symptoms in travelers of around 35%, increasing to nearly 65% in the context of mass gatherings. Common viral and bacterial pathogens account for the majority of respiratory infections with an identified cause; however, recent data focus on the need for surveillance of emerging infections such as MERS-CoV, henipaviruses and multidrug resistant bacteria, which may be spread through travel. Fungal and parasitic respiratory infections are less common, and acquisition is usually associated with specific risk factors or exposure in endemic areas. Special risk groups, such as immunocompromised travelers, may be particularly vulnerable, presenting with severe disease or reactivation of latent infections. SUMMARY: The next significant international epidemic could involve another new infectious agent causing respiratory disease and spreading via mobile populations. Official protocols should be adhered to, and public health interventions implemented for effective control. Continued and globally coordinated investments in research for new vaccines, therapeutic agents, disease modeling, and digital tracking strategies are essential.


Assuntos
Pneumonia , Infecções Respiratórias , Humanos , Pandemias , Viagem , Fatores de Risco
2.
Malar J ; 23(1): 179, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844954

RESUMO

BACKGROUND: In non-endemic countries, malaria can be transmitted through blood donations from imported cases. To ensure standards of quality and safety of human blood, the European Union and Spanish national law, requires a deferral period, or a screening by immunological or genomic test among those donors with potential risk of malaria. Scientific societies, European Committee on Blood Transfusion, and Spanish Society of Haematology and Haemotherapy, refer only to the result of the immunological test. METHODS: An observational retrospective study was performed in potential donors with a positive immunological test for malaria done in the Regional Transfusion Center in Madrid and referred to the National Reference Unit for Tropical Diseases in Madrid between 2015-2020. At consultation a Polymerase Chain Reaction (PCR) for malaria was performed. RESULTS: During the study period, 121 possible donors attended for consultation at NRU-Trop. Median age: 38.5 (IQR:33-48); median time to consultation was 32 months (IQR:12.5-110). Eighty-two (67.8%) donors were migrants and thirty-nine were travellers (32.2%). ELISA values were available for 109 subjects (90.1%), 56 individual left malaria endemic area > 3 years before. All donors tested negative for Plasmodium spp PCR test (n = 121, 100%). CONCLUSIONS: None of the subjects with a positive immunologic test deferred as blood donors had a positive genomic test. The presence of Plasmodium spp in collected blood was not detected by molecular techniques. To avoid the loss of potential blood donors, especially those with low incidence red blood cell antigens, as more precise microbiology techniques become available, updating the existing legislation becomes necessary to increase the availability of donated blood.


Assuntos
Doadores de Sangue , Malária , Estudos Retrospectivos , Humanos , Doadores de Sangue/estatística & dados numéricos , Malária/diagnóstico , Adulto , Pessoa de Meia-Idade , Masculino , Feminino , Seleção do Doador , Espanha , Reação em Cadeia da Polimerase
3.
Ann Allergy Asthma Immunol ; 130(6): 743-751.e3, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36736722

RESUMO

BACKGROUND: Clinical trials of the mRNA coronavirus disease 2019 (COVID-19) vaccines excluded individuals with primary antibody deficiencies. OBJECTIVE: To evaluate whether antibody and T-cell responses to mRNA COVID-19 vaccination in patients with common variable immunodeficiency (CVID) and specific antibody deficiency (SAD) were comparable to those in healthy controls. METHODS: We measured antibody responses against the spike glycoprotein and the receptor-binding domain (RBD) in addition to severe acute respiratory syndrome coronavirus 2 specific T-cell responses using peripheral blood mononuclear cells 2 to 8 weeks after the subjects completed the primary 2-dose vaccine series. RESULTS: The study comprised 12 patients with CVID, 7 patients with SAD, and 10 controls. Individuals with CVID had lower immunoglobulin (Ig) G and Ig A levels against spike glycoprotein than did both individuals with SAD (P = .27 and P = .01, respectively) and controls (P = .01 and P = .004, respectively). The CVID group developed lower IgG titers against the RBD epitope than did the control group (P = .01). Participants with CVID had lower neutralizing titers than did the control group (P = .002). All participants with SAD developed neutralizing titers. All 3 groups (SAD, CVID, and control) developed antigen-specific CD4+ and CD8+ T-cell responses after vaccination. CONCLUSION: Our results suggest that patients with CVID may have impaired antibody responses to COVID-19 vaccination but intact T-cell responses, whereas patients with SAD would be expected to have both intact antibody and T-cell responses to vaccination.


Assuntos
COVID-19 , Imunodeficiência de Variável Comum , Doenças da Imunodeficiência Primária , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Leucócitos Mononucleares , Vacinação , Imunoglobulina G , Glicoproteínas
4.
J Sci Food Agric ; 103(6): 3194-3204, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36534030

RESUMO

BACKGROUND: The physicochemical and functional properties of pectin (JFP) extracted from edible portions (including pericarp and seed) of raw jackfruit (an underutilized tropical fruit) at four different maturity stages (referred to as stages I, II, III, and IV) were characterized in terms of extraction yields, chemical composition, molecular weight, and antioxidant properties to evaluate its potential use in foods. RESULT: The JFP yield increased from 9.7% to 21.5% with fruit maturity, accompanied by an increase in the galacturonic acid content (50.1%, 57.1%, 63.6%, and 65.2%) for stages I-IV respectively. The molecular weight increased from 147 kDa in stage I to 169 kDa in stage III, but decreased to 114 kDa in stage IV, probably due to cell-wall degradation during maturation. The JFP was of the high methoxyl type and the degree of esterification increased from 65% to 87% with fruit maturity. The functional properties of JFP were similar to or better than those reported for commercial apple pectin, thus highlighting its potential as a food additive. Although the phenolics and flavonoids content of JFP decreased with fruit maturity, their antioxidant capacity increased, which may be correlated with the increased content of galacturonic acid upon fruit development. Gels prepared from JFP showed viscoelastic behavior. Depending on the maturity stage in which they were obtained, different gelation behavior was seen. CONCLUSION: The study confirmed the potential of pectin extracted from edible parts of jackfruit as a promising source of high-quality gelling pectin with antioxidant properties, for food applications. © 2022 Society of Chemical Industry.


Assuntos
Artocarpus , Pectinas , Pectinas/química , Artocarpus/química , Antioxidantes/análise , Frutas/química
5.
J Virol ; 95(5)2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33361434

RESUMO

Reactivation of latent HIV-1 is a necessary step for the purging of the viral reservoir, although it does not seem to be enough. The stimulation of HIV-1 specific cytotoxic T lymphocytes (CTL) may be just as essential for this purpose. In this study, we aimed to show the effect of galectin-9 (Gal-9), known to revert HIV-1 latency, in combination with the blockade of TIM-3, a natural receptor for Gal-9 and an exhaustion marker. We confirmed the ability of Gal-9 to reactivate latent HIV-1 in Jurkat-LAT-GFP cells, as well as in an IL-7-based cellular model. This reactivation was not mediated via the TIM-3 receptor, but rather by the recognition of the Gal-9 of a specific oligosaccharide pattern of resting memory CD4+ T cells' surfaces. The potency of Gal-9 in inducing transcription of latent HIV-1 was equal to or greater than that of other latency-reversing agents (LRA). Furthermore, the combination of Gal-9 with other LRA did not show synergistic effects in the reactivation of the latent virus. To evaluate the impact of TIM-3 inhibition on the CTL-response, different co-culture experiments with CD4+T, CD8+ T, and NK cells were performed. Our data showed that blocking TIM-3 was associated with control of viral replication in both in vitro and ex vivo models in cells from PLWH on antiretroviral therapy. A joint strategy of the use of Gal-9 to reactivate latent HIV-1 and the inhibition of TIM-3 to enhance the HIV-1 CTL specific-response was associated with control of the replication of the virus that was being reactivated, thus potentially contributing to the elimination of the viral reservoir. Our results place this strategy as a promising approach to be tested in future studies. Reactivation of latent-HIV-1 by Gal-9 and reinvigoration of CD8+ T cells by TIM-3 blockade could be used separately or in combination.ImportanceHIV-1 infection is a health problem of enormous importance that still causes significant mortality. Antiretroviral treatment (ART) has demonstrated efficacy in the control of HIV-1 replication, decreasing the morbidity and mortality of the infection, but it cannot eradicate the virus. In our work, we tested a protein, galectin-9 (Gal-9), an HIV-1 latency-reversing agent, using an in vitro cellular model of latency and in cells from people living with HIV-1 (PLWH) on antiretroviral therapy. Our results confirmed the potential role of Gal-9 as a molecule with a potent HIV-1 reactivation capacity. More importantly, using a monoclonal antibody against T cell immunoglobulin and the mucin domain-containing molecule 3 (TIM-3) receptor we were able to enhance the HIV-1 cytotoxic T lymphocytes (CTL) specific response to eliminate the CD4+ T cells in which the virus had been reactivated. When used together, i.e., Gal-9 and TIM-3 blockade, control of the replication of HIV-1 was observed, suggesting a decrease in the cellular reservoir.

6.
Eur J Clin Microbiol Infect Dis ; 41(6): 981-987, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35568743

RESUMO

Among 1655 consecutive patients with infective endocarditis treated from 1998 to 2020 in three tertiary care centres, 16 were caused by Candida albicans (CAIE, n = 8) and Candida parapsilosis (CPIE, n = 8). Compared to CAIE, CPIE were more frequently community-acquired. Prosthetic valve involvement was remarkably more common among patients with CPIE. CPIE cases presented a higher rate of positive blood cultures at admission, persistently positive blood cultures after antifungals initiation and positive valve cultures. All patients but four underwent cardiac surgery. Urgent surgery was more frequently performed in CPIE. No differences regarding in-hospital mortality were documented, even after adjusting for therapeutic management.


Assuntos
Endocardite Bacteriana , Endocardite , Candida albicans , Candida parapsilosis , Estudos de Coortes , Endocardite/diagnóstico , Endocardite/tratamento farmacológico , Endocardite/microbiologia , Humanos
7.
Apoptosis ; 26(1-2): 83-95, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33387147

RESUMO

We previously showed that fluorizoline, a fluorinated thiazoline compound, binds to both subunits of the mitochondrial prohibitin (PHB) complex, PHB1 and PHB2, being the expression of these proteins required for fluorizoline-induced apoptosis in mouse embryonic fibroblasts. To investigate the conservation of this apoptotic mechanism, we studied the effect of PHB downregulation on fluorizoline activity on two human cell lines, HEK293T and U2OS. Then, we asked whether PHBs mediate the effect of fluorizoline in a multicellular organism. Interestingly, reduced levels of PHBs in the human cells impaired the induction of apoptosis by fluorizoline. We observed that fluorizoline has a detrimental dose-dependent effect on the development and survival of the nematode model Caenorhabditis elegans. Besides, such effects of fluorizoline treatment in living nematodes were absent in PHB mutants. Finally, we further explored the apoptotic pathway triggered by fluorizoline in human cell lines. We found that the BH3-only proteins NOXA, BIM and PUMA participate in fluorizoline-induced apoptosis and that the induction of NOXA and PUMA is dependent on PHB expression.


Assuntos
Apoptose/efeitos dos fármacos , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/citologia , Proteínas Repressoras/metabolismo , Tiazolidinas/farmacologia , Animais , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Células HEK293 , Humanos , Proibitinas , Proteínas Repressoras/genética , Tiazolidinas/química
8.
Int J Equity Health ; 20(1): 41, 2021 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-33472644

RESUMO

BACKGROUND: There is little verified information on global healthcare utilization by irregular migrants. Understanding how immigrants use healthcare services based on their needs is crucial to establish effective health policy. We compared healthcare utilization between irregular migrants, documented migrants, and Spanish nationals in a Spanish autonomous community. METHODS: This retrospective, observational study included the total adult population of Aragon, Spain: 930,131 Spanish nationals; 123,432 documented migrants; and 17,152 irregular migrants. Healthcare utilization data were compared between irregular migrants, documented migrants and Spanish nationals for the year 2011. Multivariable standard or zero-inflated negative binomial regression models were generated, adjusting for age, sex, length of stay, and morbidity burden. RESULTS: The average annual use of healthcare services was lower for irregular migrants than for documented migrants and Spanish nationals at all levels of care analyzed: primary care (0.5 vs 4 vs 6.7 visits); specialized care (0.2 vs 1.8 vs 2.9 visits); planned hospital admissions (0.3 vs 2 vs 4.23 per 100 individuals), unplanned hospital admissions (0.5 vs 3.5 vs 5.2 per 100 individuals), and emergency room visits (0.4 vs 2.8 vs 2.8 per 10 individuals). The average annual prescription drug expenditure was also lower for irregular migrants (€9) than for documented migrants (€77) and Spanish nationals (€367). These differences were only partially attenuated after adjusting for age, sex, and morbidity burden. CONCLUSIONS: Under conditions of equal access, healthcare utilization is much lower among irregular migrants than Spanish nationals (and lower than that of documented migrants), regardless of country of origin or length of stay in Spain.


Assuntos
Utilização de Instalações e Serviços , Serviços de Saúde , Migrantes , Adolescente , Adulto , Idoso , Utilização de Instalações e Serviços/estatística & dados numéricos , Feminino , Serviços de Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha , Migrantes/estatística & dados numéricos , Adulto Jovem
9.
Int J Equity Health ; 19(1): 113, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631325

RESUMO

BACKGROUND: There is little verified information on the global health status of undocumented migrants (UMs). Our aim is to compare the prevalence of the main chronic diseases and of multimorbidity in undocumented migrants, documented migrants, and Spanish nationals in a Spanish autonomous community. METHODS: Retrospective observational study of all users of the public health system of the region of Aragon over 1 year (2011): 930,131 Spanish nationals; 123,432 documented migrants (DMs); and 17,152 UMs. Binary logistic regression was performed to examine the association between migrant status (Spanish nationals versus DMs and UMs) and both multimorbidity and individual chronic diseases, adjusting for age and sex. RESULTS: The prevalence of individual chronic diseases in UMs was lower than in DMs and much lower than in Spanish nationals. Comparison with the corresponding group of Spanish nationals revealed odds ratios (OR) of 0.1-0.3 and 0.3-0.5 for male and female UMs, respectively (p < 0.05 in all cases). The risk of multimorbidity was lower for UMs than DMs, both for men (OR, 0.12; 95%CI 0.11-0.13 versus OR, 0.53; 95%CI 0.51-0.54) and women (OR, 0.18; 95%CI 0.16-0.20 versus OR, 0.74; 95%CI 0.72-0.75). CONCLUSIONS: Analysis of data from a health system that offers universal coverage to all immigrants, irrespective of legal status, reveals that the prevalence of chronic disease and multimorbidity is lower in UMs as compared with both DMs and Spanish nationals. These findings refute previous claims that the morbidity burden in UM populations is higher than that of the native population of the host country.


Assuntos
Doença Crônica/epidemiologia , Emigrantes e Imigrantes , Nível de Saúde , Multimorbidade , Migrantes , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Atenção à Saúde , Documentação , Feminino , Humanos , Jurisprudência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Razão de Chances , Prevalência , Estudos Retrospectivos , Espanha/epidemiologia , Adulto Jovem
10.
Mar Drugs ; 17(7)2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31324025

RESUMO

Posidonia oceanica waste biomass has been valorised to produce extracts by means of different methodologies and their bioactive properties have been evaluated. Water-based extracts were produced using ultrasound-assisted and hot water methods and classified according to their ethanol-affinity (E1: ethanol soluble; E2: non-soluble). Moreover, a conventional protocol with organic solvents was applied, yielding E3 extracts. Compositional and structural characterization confirmed that while E1 and E3 extracts were mainly composed of minerals and lipids, respectively, E2 extracts were a mixture of minerals, proteins and carbohydrates. All the extracts showed remarkably high antioxidant capacity, which was not only related to phenolic compounds but also to the presence of proteins and polysaccharides. All E2 and E3 extracts inhibited the growth of several foodborne fungi, while only E3 extracts decreased substantially the infectivity of feline calicivirus and murine norovirus. These results show the potential of P. oceanica waste biomass for the production of bioactive extracts.


Assuntos
Alismatales/química , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacocinética , Animais , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Biomassa , Infecções por Caliciviridae/tratamento farmacológico , Infecções por Caliciviridae/virologia , Calicivirus Felino/efeitos dos fármacos , Gatos , Etanol/química , Doenças Transmitidas por Alimentos/microbiologia , Doenças Transmitidas por Alimentos/prevenção & controle , Humanos , Lipídeos/química , Lipídeos/isolamento & purificação , Lipídeos/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Fungos Mitospóricos/efeitos dos fármacos , Norovirus/efeitos dos fármacos , Fenóis/química , Fenóis/isolamento & purificação , Fenóis/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Proteínas de Plantas/química , Proteínas de Plantas/isolamento & purificação , Proteínas de Plantas/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Células RAW 264.7 , Solventes/química , Água/química
11.
BMC Biol ; 16(1): 36, 2018 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-29598825

RESUMO

BACKGROUND: Advances in automated image-based microscopy platforms coupled with high-throughput liquid workflows have facilitated the design of large-scale screens utilising multicellular model organisms such as Caenorhabditis elegans to identify genetic interactions, therapeutic drugs or disease modifiers. However, the analysis of essential genes has lagged behind because lethal or sterile mutations pose a bottleneck for high-throughput approaches, and a systematic way to analyse genetic interactions of essential genes in multicellular organisms has been lacking. RESULTS: In C. elegans, non-conditional lethal mutations can be maintained in heterozygosity using chromosome balancers, commonly expressing green fluorescent protein (GFP) in the pharynx. However, gene expression or function is typically monitored by the use of fluorescent reporters marked with the same fluorophore, presenting a challenge to sort worm populations of interest, particularly at early larval stages. Here, we develop a sorting strategy capable of selecting homozygous mutants carrying a GFP stress reporter from GFP-balanced animals at the second larval stage. Because sorting is not completely error-free, we develop an automated high-throughput image analysis protocol that identifies and discards animals carrying the chromosome balancer. We demonstrate the experimental usefulness of combining sorting of homozygous lethal mutants and automated image analysis in a functional genomic RNA interference (RNAi) screen for genes that genetically interact with mitochondrial prohibitin (PHB). Lack of PHB results in embryonic lethality, while homozygous PHB deletion mutants develop into sterile adults due to maternal contribution and strongly induce the mitochondrial unfolded protein response (UPRmt). In a chromosome-wide RNAi screen for C. elegans genes having human orthologues, we uncover both known and new PHB genetic interactors affecting the UPRmt and growth. CONCLUSIONS: The method presented here allows the study of balanced lethal mutations in a high-throughput manner. It can be easily adapted depending on the user's requirements and should serve as a useful resource for the C. elegans community for probing new biological aspects of essential nematode genes as well as the generation of more comprehensive genetic networks.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Citometria de Fluxo/métodos , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Mitocôndrias/metabolismo , Mutação , Proibitinas
12.
Development ; 141(22): 4366-74, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25344076

RESUMO

During the development of the central nervous system, neural progenitors generate an enormous number of distinct types of neuron and glial cells by asymmetric division. Intrinsic genetic programs define the combinations of transcription factors that determine the fate of each cell, but the precise mechanisms by which all these factors are integrated at the level of individual cells are poorly understood. Here, we analyzed the specification of the neurons in the ventral nerve cord of Drosophila that express Crustacean cardioactive peptide (CCAP). There are two types of CCAP neurons: interneurons and efferent neurons. We found that both are specified during the Hunchback temporal window of neuroblast 3-5, but are not sibling cells. Further, this temporal window generates two ganglion mother cells that give rise to four neurons, which can be identified by the expression of empty spiracles. We show that the expression of Hunchback in the neuroblast increases over time and provide evidence that the absolute levels of Hunchback expression specify the two different CCAP neuronal fates.


Assuntos
Diferenciação Celular/fisiologia , Sistema Nervoso Central/embriologia , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila/embriologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Neurônios/metabolismo , Neuropeptídeos/metabolismo , Fatores de Transcrição/metabolismo , Animais , Bromodesoxiuridina , Sistema Nervoso Central/citologia , Regulação da Expressão Gênica no Desenvolvimento/genética , Imuno-Histoquímica , Microscopia Confocal , Neurônios/citologia
13.
Int J Geriatr Psychiatry ; 32(8): 922-930, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27428560

RESUMO

OBJECTIVE: Apathy is one of the most frequent symptoms of dementia, whose underlying neurobiology is not well understood. The objective was to analyze the correlations of apathy and its dimensions with gray and white matter damage in the brain of patients with advanced Alzheimer's disease (AD). METHODS: The setting of the study was at the Alzheimer Center Reina Sofía Foundation Research Unit. Participants include 37 nursing home patients with moderate to severe AD, 78.4% were women, and mean Standard Deviation (SD) age is 82.7 (5.8). Several measurements were taken: severe mini-mental state examination and Global Deterioration Scale for cognitive and functional status, Neuropsychiatric Inventory for behavioral problems, and Apathy In Dementia-Nursing Home Version Scale for apathy, including total score and subscores of emotional blunting, deficit of thinking, and cognitive inertia. 3T magnetic resonance imaging measures (voxel-based morphometry, fluid-attenuated inversion recovery, and diffusion tensor imaging) were also conducted. RESULTS: Moderate levels of apathy (mean Apathy In Dementia-Nursing Home Version Scale: 31.1 ± 18.5) were found. Bilateral damage to the corpus callosum and internal capsule was associated with apathy severity (cluster size 2435, p < 0.0005, family-wise error [FWE]-corrected). A smaller and more anteriorly located region of the right internal capsule and corpus callosum was associated with higher emotional blunting (cluster size 334, p < 0.0005, FWE-corrected). Ischemic damage in the right periventricular frontal region was associated with higher deficit of thinking (cluster size 3805, p < 0.005, FWE-corrected). CONCLUSIONS: Brain damage related to apathy may have different features in the advanced stages of AD and differs between the three apathy dimensions. Besides atrophy, brain connectivity and vascular lesions are relevant in the study of apathy, especially in the more severe stages of dementia. Further magnetic resonance imaging studies should include multimodal techniques. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Doença de Alzheimer/fisiopatologia , Apatia/fisiologia , Substância Cinzenta/patologia , Substância Branca/patologia , Idoso , Idoso de 80 Anos ou mais , Atrofia/patologia , Imagem de Tensor de Difusão/métodos , Feminino , Lobo Frontal/patologia , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Substância Branca/diagnóstico por imagem
14.
Biochim Biophys Acta ; 1847(11): 1457-68, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26092086

RESUMO

The mitochondrial prohibitin complex, composed of two proteins, PHB-1 and PHB-2, is a context-dependent modulator of longevity. Specifically, prohibitin deficiency shortens the lifespan of otherwise wild type worms, while it dramatically extends the lifespan under compromised metabolic conditions. This extremely intriguingly phenotype has been linked to alterations in mitochondrial function and in fat metabolism. However, the true function of the mitochondrial prohibitin complex remains elusive. Here, we used gas chromatography coupled to a flame ionization detector (GC/FID) and ¹H NMR spectroscopy to gain molecular insights into the effect of prohibitin depletion on the Caenorhabditis elegans metabolome. We analysed the effect of prohibitin deficiency in two different developmental stages and under two different conditions, which result in opposing longevity phenotypes, namely wild type worms and daf-2(e1370) insulin signalling deficient mutants. Prohibitin depletion was shown to alter the fatty acid (GC/FID) and ¹H NMR metabolic profiles of wild type animals both at the fourth larval stage of development (L4) and at the young adult (YA) stage, while being more pronounced at the later stage. Furthermore, wild type and the diapause mutant daf-2(e1370), either expressing or not prohibitin, were clearly distinguishable based on their metabolic profiles, revealing changes in fatty acid composition, as well as in carbohydrate and amino acid metabolism. Moreover, the metabolic data indicate that daf-2(e1370) mutants are more robust than the wild type animals to changes induced by prohibitin depletion. The impact of prohibitin depletion on the C. elegans metabolome will be discussed herein in the scope of its effect on longevity. This article is part of a Special Issue entitled: Mitochondrial Dysfunction in Aging. Guest Editor: Aleksandra Trifunovic.


Assuntos
Caenorhabditis elegans/metabolismo , Longevidade , Metaboloma , Mitocôndrias/fisiologia , Proteínas Repressoras/fisiologia , Animais , Proteínas de Caenorhabditis elegans , Ácidos Graxos/análise , Espectroscopia de Ressonância Magnética , Proibitinas
15.
Development ; 140(10): 2139-48, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23633511

RESUMO

Although the Hox genes are the main factors involved in the generation of diversity along the anterior/posterior body axis of segmented organisms, it is still largely unknown how these genes act in single cells to determine specific traits at precise developmental stages. The aim of this study was to understand the mechanisms by which Hox genes of the Bithorax complex (Bx-C) of Drosophila act to define segmental differences in the ventral nerve cord of the central nervous system. To achieve this, we have focused on the specification of the leucokinin-expressing neurons. We find that these neurons are specified from the same progenitor neuroblast at two different developmental stages: embryonic and larval neurogenesis. We show that genes of the Bx-C acted in postmitotic cells to specify the segment-specific appearance of leucokinergic cells in the larval and adult ventral nerve cord.


Assuntos
Drosophila melanogaster/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/metabolismo , Sistema Nervoso/embriologia , Animais , Padronização Corporal , Linhagem da Célula , Sistema Nervoso Central/embriologia , Sistema Nervoso Central/metabolismo , Cruzamentos Genéticos , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Genótipo , Imuno-Histoquímica , Neuropeptídeos/metabolismo , Fenótipo , Células-Tronco/citologia , Fatores de Tempo
16.
Soft Matter ; 12(5): 1534-49, 2016 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-26658920

RESUMO

Small angle neutron scattering (SANS) has been applied to characterise the structure of pure bacterial cellulose hydrogels, and composites thereof, with two plant cell wall polysaccharides (arabinoxylan and xyloglucan). Conventional published models, which assume that bacterial cellulose ribbons are solid one-phase systems, fail to adequately describe the SANS data of pure bacterial cellulose. Fitting of the neutron scattering profiles instead suggests that the sub-structure of cellulose microfibrils contained within the ribbons results in the creation of regions with distinct values of neutron scattering length density, when the hydrogels are subjected to H2O/D2O exchange. This may be represented within a core-shell formalism that considers the cellulose ribbons to comprise a core containing impermeable crystallites surrounded by a network of paracrystalline cellulose and tightly bound water, and a shell containing only paracrystalline cellulose and water. Accordingly, a fitting function comprising the sum of a power-law term to account for the large scale structure of intertwined ribbons, plus a core-shell cylinder with polydisperse radius, has been applied; it is demonstrated to simultaneously describe all SANS contrast variation data of pure and composite bacterial cellulose hydrogels. In addition, the resultant fitting parameters indicate distinct interaction mechanisms of arabinoxylan and xyloglucan with cellulose, revealing the potential of this approach to investigate the role of different plant cell wall polysaccharides on the biosynthesis process of cellulose.


Assuntos
Bactérias/química , Parede Celular/química , Celulose/química , Hidrogéis/química , Plantas/química , Polissacarídeos/química , Espalhamento a Baixo Ângulo , Parede Celular/metabolismo , Medição da Troca de Deutério , Glucanos/química , Gluconacetobacter xylinus/metabolismo , Difração de Nêutrons , Plantas/metabolismo , Xilanos/química
17.
Nature ; 461(7265): 793-7, 2009 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-19812672

RESUMO

Marked alterations in cellular energy metabolism are a universal hallmark of the ageing process. The biogenesis and function of mitochondria, the energy-generating organelles in eukaryotic cells, are primary longevity determinants. Genetic or pharmacological manipulations of mitochondrial activity profoundly affect the lifespan of diverse organisms. However, the molecular mechanisms regulating mitochondrial biogenesis and energy metabolism during ageing are poorly understood. Prohibitins are ubiquitous, evolutionarily conserved proteins, which form a ring-like, high-molecular-mass complex at the inner membrane of mitochondria. Here, we show that the mitochondrial prohibitin complex promotes longevity by modulating mitochondrial function and fat metabolism in the nematode Caenorhabditis elegans. We found that prohibitin deficiency shortens the lifespan of otherwise wild-type animals. Notably, knockdown of prohibitin promotes longevity in diapause mutants or under conditions of dietary restriction. In addition, prohibitin deficiency extends the lifespan of animals with compromised mitochondrial function or fat metabolism. Depletion of prohibitin influences ATP levels, animal fat content and mitochondrial proliferation in a genetic-background- and age-specific manner. Together, these findings reveal a novel mechanism regulating mitochondrial biogenesis and function, with opposing effects on energy metabolism, fat utilization and ageing in C. elegans. Prohibitin may have a similar key role in modulating energy metabolism during ageing in mammals.


Assuntos
Envelhecimento/fisiologia , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/metabolismo , Mitocôndrias/metabolismo , Proteínas Repressoras/metabolismo , Transdução de Sinais , Trifosfato de Adenosina/metabolismo , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans , Restrição Calórica , Metabolismo Energético/genética , Metabolismo Energético/fisiologia , Técnicas de Silenciamento de Genes , Mucosa Intestinal/metabolismo , Metabolismo dos Lipídeos/genética , Metabolismo dos Lipídeos/fisiologia , Longevidade/genética , Longevidade/fisiologia , Mitocôndrias/fisiologia , Mutação/genética , Proibitinas , Proteínas Repressoras/genética
18.
J Nanosci Nanotechnol ; 15(1): 616-27, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26328414

RESUMO

The present study reports on the development of hybrid poly(lactic acid) (PLA) fibres loaded with highly crystalline bacterial cellulose nanowhiskers (BCNW) by the novel solution blow spinning method. Furthermore, fibres with antimicrobial properties were generated by incorporating carvacrol and THC as antimicrobial agents and the biocide effect against Listeria monocytogenes was studied. Initially, PLA blow spun fibres containing BCNW were optimized in terms of morphology and thermal properties. The addition of BCNW was seen to significantly increase the viscosity and surface tension of solutions, restricting the capacity to form fibres for concentrations greater than 30 wt.-% BCNW. 15 wt.-% BCNW was selected as the optimum nanofiller loading as it led to the most uniform fibres morphology, with BCNW homogeneously distributed along the fibres' axis. Subsequently, carvacrol and THC were incorporated into the fibres to confer them with antimicrobial properties, although the hydrophobic PLA matrix did not provide an efficient release of the antimicrobials. Thus, hydrophilic substances were added in order to trigger the antimicrobials release through water sorption mechanisms. The addition of the BCNW filler was not seen to significantly increase the antimicrobial capacity of the fibres by itself and, hence, gelatin was added to help promoting further the hydrophylicity and biocide performance of the fibres. Nevertheless, for the more hydrophilic THC, the biocide capacity of the fibres with gelatin was accentuated further by the presence of the BCNW.


Assuntos
Anti-Infecciosos/química , Ácido Láctico/química , Nanofibras/química , Nanotecnologia/métodos , Polímeros/química , Anti-Infecciosos/farmacologia , Varredura Diferencial de Calorimetria , Celulose/química , Celulose/metabolismo , Cimenos , Gluconacetobacter xylinus/química , Gluconacetobacter xylinus/metabolismo , Listeria monocytogenes/efeitos dos fármacos , Monoterpenos/química , Monoterpenos/farmacologia , Poliésteres , Viscosidade
19.
Dev Dyn ; 243(3): 402-14, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24155257

RESUMO

BACKGROUND: The Drosophila central nervous system contains many types of neurons that are derived from a limited number of progenitors as evidenced in the ventral ganglion. The situation is much more complex in the developing brain. The main neuronal structures in the adult brain are generated in the larval neurogenesis, although the basic neuropil structures are already laid down during embryogenesis. The embryonic factors involved in adult neuron origin are largely unknown. To shed light on how brain cell diversity is achieved, we studied the early temporal and spatial cues involved in the specification of lateral horn leucokinin peptidergic neurons (LHLKs). RESULTS: Our analysis revealed that these neurons have an embryonic origin. We identified their progenitor neuroblast as Pcd6 in the Technau and Urbach terminology. Evidence was obtained that a temporal series involving the transcription factors Kr, Pdm, and Cas participates in the genesis of the LHLK lineage, the Castor window being the one in which the LHLKs neurons are generated. It was also shown that Notch signalling and Dimmed are involved in the specification of the LHLKs. CONCLUSIONS: Serial homologies with the origin and factors involved in specification of the abdominal leucokinergic neurons (ABLKs) have been detected.


Assuntos
Encéfalo , Proteínas de Drosophila/biossíntese , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Células-Tronco Neurais/metabolismo , Neurogênese/fisiologia , Neurópilo , Fatores de Transcrição/biossíntese , Animais , Encéfalo/citologia , Encéfalo/embriologia , Proteínas de Drosophila/genética , Drosophila melanogaster , Células-Tronco Neurais/citologia , Neurópilo/citologia , Neurópilo/metabolismo , Fatores de Transcrição/genética
20.
Clin Infect Dis ; 59(4): 552-5, 2014 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-24814660

RESUMO

Although human immunodeficiency virus (HIV) and visceral leishmaniasis coinfection is recognized as a major public health challenge in Africa, data regarding the prevalence in India are very limited. Consecutive HIV screening of 2077 patients aged ≥14 years with confirmed visceral leishmaniasis in Bihar, eastern India, found that 5.6% were HIV positive, including 2.4% with newly diagnosed HIV infection.


Assuntos
Coinfecção/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Leishmaniose Visceral/complicações , Leishmaniose Visceral/epidemiologia , Adolescente , Adulto , Idoso , Coinfecção/parasitologia , Coinfecção/virologia , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
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