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1.
J Environ Manage ; 329: 117062, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36549052

RESUMO

Soil contamination by pesticides is a growing environmental problem. Even though nowadays numerous soil remediation technologies are available, most of them have not been tested at field scale. This study attempts to demonstrate the efficiency of solarization-ozonation techniques for the removal of twelve pesticides at full scale. Initial solarization and ozonation trials were conducted in plots located in a greenhouse using freshly and aged contaminated soils under controlled pilot conditions. The combination of solarization and ozonation treatment was efficient for all the studied pesticides both in freshly and in aged contaminated soils, being the lower degradation values found for the second type. This low removal suggests that the increase of pesticides' adsorption on soil resulting from ageing decreases their availability. Once the essays were carried out at pilot scale, the solarization-ozonation applicability was evaluated in a commercial farm soil. This trial was carried out in a greenhouse whose soil had previously been contaminated with some of the pesticides studied. A significant degradation (53.8%) was observed after 40 days of treatment. Pesticides' main metabolites were identified during the different remediation experiments. In addition, the cost of the combined solarization and ozonation technology was evaluated. Finally, our results suggest that this combination of techniques could be considered a promising technology to degrade pesticides in soil.


Assuntos
Recuperação e Remediação Ambiental , Ozônio , Praguicidas , Poluentes do Solo , Praguicidas/análise , Solo , Fazendas , Poluição Ambiental , Poluentes do Solo/análise
2.
Benef Microbes ; 14(6): 553-564, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38350472

RESUMO

Exercise induces many health benefits, preventing or treating diseases. On the other hand, the intestine houses trillions of microbes with the ability to influence the normal physiology of the organism. The intestinal microbiota is immensely diverse, varies between individuals, and can fluctuate according to various factors, including physical activity. In this sense, the aim of this systematic review is to search through the recent knowledge, in order to elucidate the roles played by different exercise modalities on modulation of the intestinal microbiota of adults. A literature search was performed in the PubMed, SCOPUS and Web of Science databases. The main inclusion criteria were randomised controlled trials involving exercise and microbiota in adults. The initial search identified 1,103 publications of which 13 were finally included. The heterogeneity of the training parameters used in the studies, statistical analyses, and sequencing methods did not allow us to carry out a meta-analysis. However, the results tend to show that modulation of the gut microbiome is related to the type of exercise, the intensity and the time of intervention, where these changes are more significant at the level of specific microbial populations than richness and diversity indices.


Assuntos
Microbioma Gastrointestinal , Microbiota , Probióticos , Adulto , Humanos , Microbioma Gastrointestinal/fisiologia , Exercício Físico/fisiologia , Intestinos , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
J Prev Alzheimers Dis ; 9(4): 601-616, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36281664

RESUMO

OBJECTIVE: A systematic review of randomized controlled trials was conducted to determine the effect of physical exercise on physical-functional capacity, cognitive performance, neuropsychiatric symptoms, and quality of life in a population of older people with Alzheimer´s disease. DATA SOURCES: Pubmed, Scopus, PEDro, Web of Science, CINAHL, Cochrane Library, grey literature and a reverse search from inception to April 2021 were searched to identify documents. STUDY SELECTION: Publications investigating the effect of any type of physical exercise-based intervention in any of its multiple modalities on physical-functional capacity, cognitive performance, neuropsychiatric symptoms, and quality of life were searched. DATA EXTRACTION: The data were extracted into predesigned data extraction tables. Risk of bias was evaluated through the PEDro scale and its internal validity scale. DATA SYNTHESIS: A total of 8 different randomized controlled trials with a total sample of 562 non-overlap Alzheimer disease patients between 50-90 years and a mean age of 75.2 ± 3.9 years were eligible for analyses. Physical-functional capacity was evaluated in 6 of 8 studies and cognitive performance was evaluated in 5 of 8 studies, all of them showed improvements in these variables when compared with the controls, except for two studies in physical-functional capacity and one study for cognitive performance. In the physical-functional capacity and cognitive performance variables, aerobic physical exercise was used in isolation, or in a multimodal way, combining aerobic, strength and balance exercise, from 2 to 7 weekly sessions with doses between 30 and 90 minutes, and a duration of the program comprised of 9 weeks to 6 months. Neuropsychiatric symptoms and quality of life were evaluated in 2 of 8 studies, which the intervention groups experienced significant improvements when compared with the control groups, except for one study that found similar differences in quality of life between both groups. In the neuropsychiatric symptoms and quality of life variables, only aerobic physical exercise was used, in a more homogeneous way, from 2 to 3 weekly sessions with doses of 30 to 60 minutes, and a total program duration of 9 to 16 weeks. CONCLUSIONS: Despite the scarcity of studies, especially those based on multimodal proposals, and the heterogeneity in the protocols, this systematic review found moderate to limited evidence that aerobic physical exercise on its own or combined in a multimodal program that also includes strength and balance exercise can be a useful tool in the management of patients with Alzheimer's disease with the aim of maintaining and/or improving physical-functional capacity and cognitive performance. In addition, this review found moderate evidence of the positive impact that aerobic physical exercise could have in reducing neuropsychiatric symptoms and improving quality of life in patients with Alzheimer´s disease. PROSPERO registration number: CRD42021229891.


Assuntos
Doença de Alzheimer , Terapia por Exercício , Exercício Físico , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/terapia , Exercício Físico/fisiologia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
4.
Med Oral Patol Oral Cir Bucal ; 27(1): e77-e84, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34564679

RESUMO

BACKGROUND: MiRNAs are small non-coding RNAs that regulate gene expression at the post-transcriptional level and have been associated with malignant transformation of oral epithelial precursor lesions such as oral leukoplakia. The aim was to perform a scoping review of the contemporary literature about the different roles of miRNAs during the malignant transformation of oral leukoplakia. MATERIAL AND METHODS: We conducted a systematic search with the following MeSH terms: 'oral leukoplakia', 'carcinoma in situ', 'microRNAs', 'mouth neoplasms' and 'epithelial-mesenchymal transition' in PubMed/MEDLINE, EMBASE and SpringerLink. RESULTS: Fifteen articles were included for analysis, among which in vivo and in vitro articles were included. A total of 21 different miRNAs were found to be involved in the malignant transformation process of oral leukoplakia. Regarding their possible effects, 6 miRNAs were classified as oncogenic, 5 as tumour suppressors and 10 were related to epithelial-mesenchymal transition, invasion and migration. CONCLUSIONS: Based on the current review, we concluded that miRNAs-21, 345, 181-b and 31* seem to be potential markers of malignant transformation of oral leukoplakia. However, further clinical prospective studies are needed in order to validate their utility as prognostic biomarkers.


Assuntos
MicroRNAs , Neoplasias Bucais , Transformação Celular Neoplásica/genética , Humanos , Leucoplasia Oral/genética , MicroRNAs/genética , Estudos Prospectivos
5.
Biochim Biophys Acta Biomembr ; 1864(1): 183813, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34748743

RESUMO

Cellular membranes are fundamental building blocks regulating an extensive repertoire of biological functions. These structures contain lipids and membrane proteins that are known to laterally self-aggregate in the plane of the membrane, forming defined membrane nanoscale domains essential for protein activity. Membrane rafts are described as heterogeneous, dynamic, and short-lived cholesterol- and sphingolipid-enriched membrane nanodomains (10-200 nm) induced by lipid-protein and lipid-lipid interactions. Those membrane nanodomains have been extensively characterized using model membranes and in silico methods. However, despite the development of advanced fluorescence microscopy techniques, undoubted nanoscale visualization by imaging techniques of membrane rafts in the membrane of unperturbed living cells is still uncompleted, increasing the skepticism about their existence. Here, we broadly review recent biochemical and microscopy techniques used to investigate membrane rafts in living cells and we enumerate persistent open questions to answer before unlocking the mystery of membrane rafts in living cells.


Assuntos
Membrana Celular/ultraestrutura , Microdomínios da Membrana/ultraestrutura , Proteínas de Membrana/ultraestrutura , Membrana Celular/química , Membrana Celular/genética , Humanos , Transporte de Íons/genética , Microdomínios da Membrana/química , Microdomínios da Membrana/genética , Proteínas de Membrana/química , Proteínas de Membrana/genética , Esfingolipídeos/química , Esfingolipídeos/genética
6.
Small Methods ; 5(9): e2100430, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34928061

RESUMO

Despite more than 20 years of work since the lipid raft concept was proposed, the existence of these nanostructures remains highly controversial due to the lack of noninvasive methods to investigate their native nanorganization in living unperturbed cells. There is an unmet need for probes for direct imaging of nanoscale membrane dynamics with high spatial and temporal resolution in living cells. In this paper, a bioorthogonal-based cholesterol probe (chol-N3 ) is developed that, combined with nanoscopy, becomes a new powerful method for direct visualization and characterization of lipid raft at unprecedented resolution in living cells. The chol-N3 probe mimics cholesterol in synthetic and cellular membranes without perturbation. When combined with live-cell super-resolution microscopy, chol-N3 demonstrates the existence of cholesterol-rich nanodomains of <50 nm at the plasma membrane of resting living cells. Using this tool, the lipid membrane structure of such subdiffraction limit domains is identified, and the nanoscale spatiotemporal organization of cholesterol in the plasma membrane of living cells reveals multiple cholesterol diffusion modes at different spatial localizations. Finally, imaging across thick organ samples outlines the potential of this new method to address essential biological questions that were previously beyond reach.


Assuntos
Colesterol/análise , Microdomínios da Membrana/química , Imagem Molecular/métodos , Sondas Moleculares/química , Neurônios/citologia , Animais , Células Cultivadas , Colesterol/química , Células HeLa , Humanos , Microscopia de Fluorescência , Modelos Moleculares , Conformação Molecular , Neurônios/química , Ratos , Análise Espaço-Temporal
7.
Sci Adv ; 7(42): eabj4565, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34652941

RESUMO

Glycolipids are prominent components of bacterial membranes that play critical roles not only in maintaining the structural integrity of the cell but also in modulating host-pathogen interactions. PatA is an essential acyltransferase involved in the biosynthesis of phosphatidyl-myo-inositol mannosides (PIMs), key structural elements and virulence factors of Mycobacterium tuberculosis. We demonstrate by electron spin resonance spectroscopy and surface plasmon resonance that PatA is an integral membrane acyltransferase tightly anchored to anionic lipid bilayers, using a two-helix structural motif and electrostatic interactions. PatA dictates the acyl chain composition of the glycolipid by using an acyl chain selectivity "ruler." We established this by a combination of structural biology, enzymatic activity, and binding measurements on chemically synthesized nonhydrolyzable acyl­coenzyme A (CoA) derivatives. We propose an interfacial catalytic mechanism that allows PatA to acylate hydrophobic PIMs anchored in the inner membrane of mycobacteria, through the use of water-soluble acyl-CoA donors.

8.
Indian J Otolaryngol Head Neck Surg ; 73(3): 321-326, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34471620

RESUMO

Although a majority of tumors in the Cerebellopontine Angle (CPA) are vestibular schwannomas (VS), other masses can also be seen in the region and differentiation of various CPA tumors, particularly meningiomas can be difficult on imaging alone. Treatment options may vary based on specific pathology of the CPA tumor. In this study, the presence of microhemorrhage (MH) and other imaging features such as size of lesion, cystic features and pattern of IAC extension, were evaluated as a tool in distinguishing VS from other CPA masses. A review of CPA masses in the last 11 years at our institution was performed. All the pathology proven tumors with at least 1 pre-operative MRI were considered for analysis. A T2* GRE or SWI sequence was used to assess presence of MH within the lesion. Pattern of IAC extension ('centric' versus 'eccentric') of tumor was also evaluated. A total of 147 patients were reviewed out of which 102 patients (with T2* GRE or SWI) were included for analysis of MH. 57 patients (56%) had VS as the final histopathological diagnosis and 45 patients (44%) had other types of tumor. A sensitivity of 82% and a specificity of 98% was noted for the presence of MH favoring the diagnosis of VS from other tumors (p < 0.001). All meningiomas with IAC extension (25/31) showed an 'eccentric' pattern of extension into the canal. Visualization of MH and pattern of IAC extension is useful in the differentiation of schwannomas from other CPA masses, particularly meningiomas.

9.
Adv Sci (Weinh) ; 8(3): 2003468, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33552873

RESUMO

HIV-1 entry requires the redistribution of envelope glycoproteins (Env) into a cluster and the presence of cholesterol (chol) in the viral membrane. However, the molecular mechanisms underlying the specific role of chol in infectivity and the driving force behind Env clustering remain unknown. Here, gp41 is demonstrated to directly interact with chol in the viral membrane via residues 751-854 in the cytoplasmic tail (CT751-854). Super-resolution stimulated emission depletion (STED) nanoscopy analysis of Env distribution further demonstrates that both truncation of gp41 CT751-854 and depletion of chol leads to dispersion of Env clusters in the viral membrane and inhibition of virus entry. This work reveals a direct interaction of gp41 CT with chol and indicates that this interaction is an important orchestrator of Env clustering.

10.
Cuad. Hosp. Clín ; 61(2): 23-32, dic. 2020. ilus.
Artigo em Espanhol | LILACS, LIBOCS | ID: biblio-1179084

RESUMO

OBJETIVO: proponer una clasificación preoperatoria a los pacientes con tumor de cuerpo Carotídeo y relacionarlos con complicaciones postoperatorias. MATERIAL Y MÉTODOS: todos los pacientes operados con diagnóstico de tumor del cuerpo Carotídeo entre el 2005 al 2014 en el Hospital Obrero N° 1 de la Caja Nacional de Salud en La Paz - Bolivia RESULTADOS: se analizaron y operaron 115 pacientes con un promedio de edad de 52 años (DE±11,725 y una moda de 57 años) de los cuales el 109 (94,80%) correspondieron al género femenino con una razón de 18:1. Todos los pacientes eran originarios y residentes de ciudades ubicadas a más de 2500 m.s.n.m. El promedio de evolución fue de 3 años (DE±2,189), y solo 7 pacientes (6,1%) presentan hábito tabáquico. 83 pacientes (72,2%) de los TCC se localizan en el lado izquierdo En las manifestaciones clínicas, todos los pacientes presentan el tumor localizado en el ángulo mandibular, por delante del musculo esternocleidomastoideo, describiéndose un crecimiento paulatino y permanente en 72 sujetos (62,6%), cefalea en 45 (39,1%), presencia de latido en 30 sujetos (26,1%), disfagia en 9 (7,9%), mareos en 16 (13,9%) y disfonía en 6 (5,2%). Entre los signos más evidentes de TCC, se describe el signo de Fontaine en 114 sujetos (99,2%), adenomegalia en 20 (17,4%) y otros menos frecuentes como soplo, abombamiento parafaringeo y compromiso de pares craneales. Todos los pacientes fueron clasificados en ambos sistemas (Shamblin y la nuestra llamada de los Andes). Se describen 39 pacientes (33,2%) con complicaciones postoperatorias, Grado I: 1 paciente sin complicaciones; Grado II: de 58 sujetos, 4 (3,5%) presentaban parálisis temporal del Hipogloso; en el Grado III: de los 41 sujetos, 24 (20,8%) presentaron ligadura de la arteria carótida externa, parálisis del hipogloso y glosofaringeo, lesión de recurrente y del laríngeo superior. En el grupo IV, de los 15 sujetos operados, 11 presentaron complicaciones (9,6% del total y 73% del grupo) entre las cuales están ligadura de la arteria carótida externa, lesión del hipogloso y un paciente con AVC y hemiparesia. Se describe una reoperación (0,86%) y ninguna mortalidad. CONCLUSIÓN: proponer una clasificación preoperatoria que tenga la posibilidad de asociarse a complicaciones y pronóstico.


OBJECTIVE: to propose a preoperative classification of patients with Carotid Body Tumor and relate them to postoperative complications. MATERIAL AND METHODS: all patients operated with a diagnosis of Carotid Body Tumor between 2005 and 2014 at the Obrero Hospital No. 1 of the National Health Fund in La Paz - Bolivia RESULTS: 115 patients with an average age of 52 years (SD±11.725 and a mode of 57 years) were analyzed and operated on, of which 109 (94.80%) corresponded to the female gender with a ratio of 18: 1. All the patients were from and residents of cities located more than 2,500 meters above sea level. The mean evolution was 3 years (SD±2.189), and only 7 patients (6.1%) had a smoking habit. 83 patients (72.2%) of CBTs are located on the left side In the clinical manifestations, all patients present the tumor located in the mandibular angle, in front of the sternocleidomastoid muscle, describing a gradual and permanent growth in 72 subjects (62.6%), headache in 45 (39.1%), presence of heartbeat in 30 subjects (26.1%), dysphagia in 9 (7.9%), dizziness in 16 (13.9%) and dysphonia in 6 (5.2%). Among the most obvious signs of CBT, the Fontaine sign is described in 114 subjects (99.2%), adenomegaly in 20 (17.4%) and other less frequent signs such as murmur, parapharyngeal bulging and cranial nerve involvement. All patients were classified in both systems (Shamblin and ours called from the Andes). 39 patients (33.2%) with postoperative complications were described, grade I: 1 patient without complications; Grade II: of 58 subjects, 4 (3.5%) had temporary hypoglossal paralysis; in Grade III: of the 41 subjects, 24 (20.8%) presented external carotid artery ligation, hypoglossal and glossopharyngeal paralysis, recurrent lesion and superior larynx. In group IV, of the 15 operated subjects, 11 presented complications (9.6% of the total and 73% of the group), among which are external carotid artery ligation, hypoglossal injury and one patient with stroke and hemiparesis. A reoperation (0.86%) and no mortality are described. CONCLUSION: propose a preoperative classification that has the possibility of being associated with complications and prognosis.


Assuntos
Humanos , Corpo Carotídeo , Tumor do Corpo Carotídeo , Cefaleia , Sinais e Sintomas , Neoplasias
11.
Biol Res ; 53(1): 26, 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32513271

RESUMO

BACKGROUND: There is an emerging field to put into practice new strategies for developing molecules with antimicrobial properties. In this line, several metals and metalloids are currently being used for these purposes, although their cellular effect(s) or target(s) in a particular organism are still unknown. Here we aimed to investigate and analyze Au3+ toxicity through a combination of biochemical and molecular approaches. RESULTS: We found that Au3+ triggers a major oxidative unbalance in Escherichia coli, characterized by decreased intracellular thiol levels, increased superoxide concentration, as well as by an augmented production of the antioxidant enzymes superoxide dismutase and catalase. Because ROS production is, in some cases, associated with metal reduction and the concomitant generation of gold-containing nanostructures (AuNS), this possibility was evaluated in vivo and in vitro. CONCLUSIONS: Au3+ is toxic for E. coli because it triggers an unbalance of the bacterium's oxidative status. This was demonstrated by using oxidative stress dyes and antioxidant chemicals as well as gene reporters, RSH concentrations and AuNS generation.


Assuntos
Escherichia coli/efeitos dos fármacos , Ouro/toxicidade , Nanopartículas Metálicas/toxicidade , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos
12.
Psychol Med ; 50(16): 2702-2710, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-31637990

RESUMO

BACKGROUND: Social cognition has been associated with functional outcome in patients with first episode psychosis (FEP). Social cognition has also been associated with neurocognition and cognitive reserve. Although cognitive reserve, neurocognitive functioning, social cognition, and functional outcome are related, the direction of their associations is not clear. Therefore, the main aim of this study was to analyze the influence of social cognition as a mediator between cognitive reserve and cognitive domains on functioning in FEP both at baseline and at 2 years. METHODS: The sample of the study was composed of 282 FEP patients followed up for 2 years. To analyze whether social cognition mediates the influence of cognitive reserve and cognitive domains on functioning, a path analysis was performed. The statistical significance of any mediation effects was evaluated by bootstrap analysis. RESULTS: At baseline, as neither cognitive reserve nor the cognitive domains studied were related to functioning, the conditions for mediation were not satisfied. Nevertheless, at 2 years of follow-up, social cognition acted as a mediator between cognitive reserve and functioning. Likewise, social cognition was a mediator between verbal memory and functional outcome. The results of the bootstrap analysis confirmed these significant mediations (95% bootstrapped CI (-10.215 to -0.337) and (-4.731 to -0.605) respectively). CONCLUSIONS: Cognitive reserve and neurocognition are related to functioning, and social cognition mediates in this relationship.


Assuntos
Reserva Cognitiva , Funcionamento Psicossocial , Transtornos Psicóticos/psicologia , Cognição Social , Adolescente , Adulto , Feminino , Humanos , Modelos Lineares , Masculino , Análise de Mediação , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/diagnóstico , Adulto Jovem
13.
Acta Psychiatr Scand ; 141(6): 541-552, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31746462

RESUMO

AIMS: Here, we present a clustering strategy to identify phenotypes of antipsychotic (AP) response by using longitudinal data from patients presenting first-episode psychosis (FEP). METHOD: One hundred and ninety FEP with complete data were selected from the PEPs project. The efficacy was assessed using total PANSS, and adverse effects using total UKU, during one-year follow-up. We used the Klm3D method to cluster longitudinal data. RESULTS: We identified four clusters: cluster A, drug not toxic and beneficial; cluster B, drug beneficial but toxic; cluster C, drug neither toxic nor beneficial; and cluster D, drug toxic and not beneficial. These groups significantly differ in baseline demographics, clinical, and neuropsychological characteristics (PAS, total PANSS, DUP, insight, pIQ, age of onset, cocaine use and family history of mental illness). CONCLUSIONS: The results presented here allow the identification of phenotypes of AP response that differ in well-known simple and classic clinical variables opening the door to clinical prediction and application of personalized medicine.


Assuntos
Antipsicóticos/uso terapêutico , Fenótipo , Medicina de Precisão , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/psicologia , Estudos de Coortes , Feminino , Humanos , Masculino
14.
Biol. Res ; 53: 26, 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1124211

RESUMO

BACKGROUND: There Is an emerging field to put Into practice new strategies for developing molecules with antimicrobial properties. In this line, several metals and metalloids are currently being used for these purposes, although their cellular effect(s) or target(s) in a particular organism are still unknown. Here we aimed to investigate and analyze Au3+ toxicity through a combination of biochemical and molecular approaches. RESULTS: We found that Au3+ triggers a major oxidative unbalance in Escherichia coli, characterized by decreased intracellular thiol levels, increased superoxide concentration, as well as by an augmented production of the antioxidant enzymes superoxide dismutase and catalase. Because ROS production is, in some cases, associated with metal reduction and the concomitant generation of gold-containing nanostructures (AuNS), this possibility was evaluated in vivo and in vitro. CONCLUSIONS: Au3+ is toxic for E. coli because it triggers an unbalance of the bacterium's oxidative status. This was demonstrated by using oxidative stress dyes and antioxidant chemicals as well as gene reporters, RSH concentrations and AuNS generation.


Assuntos
Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Ouro/toxicidade
15.
Climacteric ; 22(5): 511-517, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31079508

RESUMO

Objectives: Around the menopause, sleep disturbances frequently occur or worsen and are associated with decreased health quality and physical and psychological problems. The aim of this study was to analyze sleep quality and its association with the impact of menopausal symptoms in Spanish postmenopausal women. Methods: A total of 278 postmenopausal women (age 60.95 ± 8.01 years) participated in this cross-sectional study. The Medical Outcomes Study Sleep Scale (MOS-SS) and the Menopause Rating Scale (MRS) were used to analyze sleep quality and severity of menopausal symptoms, respectively. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale. Results: The linear regression showed that a greater impact of menopausal symptoms (MRS total score) was associated with worse scores regarding sleep adequacy (p < 0.001, R2 = 0.056), snoring (p = 0.020, R2 = 0.036), awaken short of breath (p < 0.001, R2 = 0.089), and quantity of sleep (p < 0.001, R2 = 0.075) domains. Anxiety (p < 0.001) and worse somatic symptoms (p = 0.001) were related to greater sleep disturbances (R2 = 0.164). We also found relationships of heightened psychological symptoms (p < 0.001) and low physical activity level (p = 0.003) with increased daytime somnolence (R2 = 0.064). Finally, higher MRS total score and anxiety levels were associated with worse sleep quality assessed by MOS-SS Sleep Problems Index I (R2 = 0.179, p < 0.001 and p = 0.001, respectively) and Sleep Problems Index II (R2 = 0.146, p < 0.001 and p = 0.011, respectively). Conclusions: Anxiety and severity of menopausal symptoms were associated with poorer sleep quality. Furthermore, low physical activity level and worse psychological symptoms in menopause were predictors for increased somnolence. Therefore, screening for these factors in postmenopausal women is important, since they may be susceptible for intervention.


Assuntos
Transtornos de Ansiedade/psicologia , Pós-Menopausa , Qualidade de Vida , Transtornos do Sono-Vigília/psicologia , Sono , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Psicometria , Espanha , Inquéritos e Questionários
16.
Front Immunol ; 9: 1983, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30233582

RESUMO

The envelope of Human Immunodeficiency Virus type 1 (HIV-1) consists of a liquid-ordered membrane enriched in raft lipids and containing the viral glycoproteins. Previous studies demonstrated that changes in viral membrane lipid composition affecting membrane structure or curvature can impair infectivity. Here, we describe novel antiviral compounds that were identified by screening compound libraries based on raft lipid-like scaffolds. Three distinct molecular structures were chosen for mode-of-action studies, a sterol derivative (J391B), a sphingosine derivative (J582C) and a long aliphatic chain derivative (IBS70). All three target the viral membrane and inhibit virus infectivity at the stage of fusion without perturbing virus stability or affecting virion-associated envelope glycoproteins. Their effect did not depend on the expressed envelope glycoproteins or a specific entry route, being equally strong in HIV pseudotypes carrying VSV-G or MLV-Env glycoproteins. Labeling with laurdan, a reporter of membrane order, revealed different membrane structure alterations upon compound treatment of HIV-1, which correlated with loss of infectivity. J582C and IBS70 decreased membrane order in distinctive ways, whereas J391B increased membrane order. The compounds' effects on membrane order were reproduced in liposomes generated from extracted HIV lipids and thus independent both of virion proteins and of membrane leaflet asymmetry. Remarkably, increase of membrane order by J391B required phosphatidylserine, a lipid enriched in the HIV envelope. Counterintuitively, mixtures of two compounds with opposite effects on membrane order, J582C and J391B, did not neutralize each other but synergistically inhibited HIV infection. Thus, altering membrane order, which can occur by different mechanisms, constitutes a novel antiviral mode of action that may be of general relevance for enveloped viruses and difficult to overcome by resistance development.


Assuntos
Antivirais/uso terapêutico , Materiais Biomiméticos/uso terapêutico , Infecções por HIV/metabolismo , HIV-1/fisiologia , Lipídeos/química , Microdomínios da Membrana/metabolismo , Produtos do Gene env do Vírus da Imunodeficiência Humana/metabolismo , Antivirais/química , Materiais Biomiméticos/química , Ácidos Graxos/química , Células HEK293 , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , HIV-1/patogenicidade , Humanos , Lipídeos/uso terapêutico , Microdomínios da Membrana/química , Microdomínios da Membrana/virologia , Estrutura Molecular , Esfingosina/análogos & derivados , Esfingosina/química , Esteróis/química , Virulência , Internalização do Vírus/efeitos dos fármacos
17.
Acta Psychiatr Scand ; 138(5): 441-455, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30105820

RESUMO

OBJECTIVE: Cognitive reserve (CR) refers to the brain's capacity to cope with pathology in order to minimize the symptoms. CR is associated with different outcomes in severe mental illness. This study aimed to analyze the impact of CR according to the diagnosis of first-episode affective or non-affective psychosis (FEP). METHOD: A total of 247 FEP patients (211 non-affective and 36 affective) and 205 healthy controls were enrolled. To assess CR, common proxies have been integrated (premorbid IQ; education-occupation; leisure activities). The groups were divided into high and low CR. RESULTS: In non-affective patients, those with high CR were older, had higher socioeconomic status (SES), shorter duration of untreated psychosis, and a later age of onset. They also showed greater performance in most cognitive domains. In affective patients, those with a greater CR showed a higher SES, better functioning, and greater verbal memory performance. CONCLUSION: CR plays a differential role in the outcome of psychoses according to the diagnosis. Specifically, in order to address the needs of non-affective patients with low CR, cognitive rehabilitation treatments will need to be 'enriched' by adding pro-cognitive pharmacological agents or using more sophisticated approaches. However, a functional remediation therapy may be of choice for those with an affective psychosis and low CR.


Assuntos
Transtornos Psicóticos Afetivos/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Reserva Cognitiva/fisiologia , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/fisiopatologia , Adulto , Transtornos Psicóticos Afetivos/complicações , Fatores Etários , Idade de Início , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/terapia , Remediação Cognitiva , Feminino , Seguimentos , Humanos , Masculino , Transtornos Psicóticos/complicações , Esquizofrenia/complicações , Classe Social , Adulto Jovem
18.
J Affect Disord ; 238: 297-304, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29902733

RESUMO

OBJECTIVE: This study aimed to assess (1) whether there were clinical, neuropsychological and functional differences between and within affective and non-affective psychoses at baseline and two years-follow-up and (2) to explore clinical and neuropsychological predictors of psychosocial functioning in the whole sample. METHOD: This is a subanalysis from a multicentre, naturalistic, longitudinal prospective study ('Phenotype-genotype and environmental interaction. Application of a predictive model in first psychotic episodes'). The sample consisted of 192 patients with a first psychotic episode (FEP): 142 with non-affective psychoses and 50 with affective psychoses. Student t-tests, paired t-tests, Pearson correlations, ANOVAs and regression analyses were performed. RESULTS: At baseline, the groups differed in perseverative errors (WCST), Premorbid Adjustment Scale (PAS), family history of psychiatric disorder, negative (PANSS) and manic symptoms (YMRS). At two years follow-up, the groups differed in all the PANSS subscales and in depressive symptoms assessed by the MADRS. When the whole sample was considered, the regression model which best explained the estimated variance in functioning at follow-up (41%) was composed by PANSS total score and verbal fluency assessed by the FAS (COWAT). CONCLUSIONS: We found clinical and neurocognitive differences at baseline which decreased in the follow-up. Reduced performances at baseline in executive functions in combination with symptom severity (PANSS) were predictors of FEP patients' poor functional outcome.


Assuntos
Afeto , Transtornos Psicóticos/psicologia , Adolescente , Adulto , Análise de Variância , Depressão , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos , Análise de Regressão
19.
Sci Rep ; 8(1): 7456, 2018 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-29748552

RESUMO

The mechanisms of Pb(II) toxicity have been studied in human red blood cells using confocal microscopy, immunolabeling, fluorescence-activated cell sorting and atomic force microscopy. The process follows a sequence of events, starting with calcium entry, followed by potassium release, morphological change, generation of ceramide, lipid flip-flop and finally cell lysis. Clotrimazole blocks potassium channels and the whole process is inhibited. Immunolabeling reveals the generation of ceramide-enriched domains linked to a cell morphological change, while the use of a neutral sphingomyelinase inhibitor greatly delays the process after the morphological change, and lipid flip-flop is significantly reduced. These facts point to three major checkpoints in the process: first the upstream exchange of calcium and potassium, then ceramide domain formation, and finally the downstream scramblase activation necessary for cell lysis. In addition, partial non-cytotoxic cholesterol depletion of red blood cells accelerates the process as the morphological change occurs faster. Cholesterol could have a role in modulating the properties of the ceramide-enriched domains. This work is relevant in the context of cell death, heavy metal toxicity and sphingolipid signaling.


Assuntos
Ceramidas/metabolismo , Eritrócitos/patologia , Chumbo/toxicidade , Proteínas de Transferência de Fosfolipídeos/metabolismo , Animais , Células CHO , Cricetulus , Ativação Enzimática/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Hemólise/efeitos dos fármacos , Humanos , Chumbo/metabolismo
20.
Eur Arch Psychiatry Clin Neurosci ; 268(7): 699-711, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29164332

RESUMO

Individual changes over time in cognition in patients with psychotic disorders have been studied very little, especially in the case of first episode psychosis (FEP). We aimed to establish whether change in individual trajectories in cognition over 2 years of a sample of 159 FEP patients was reliable and clinically significant, using the reliable change index (RCI) and clinically significant change (CSC) methods. We also studied a sample of 151 matched healthy controls. Patients and controls were assessed with a set of neuropsychological tests, as well as premorbid, clinical and functionality measures. We analysed the course of cognitive measures over time, using analysis of variance, and the individual trajectories in the cognitive measures with the regression-based RCI (RCISRB) and the CSC. The RCISRB showed that between 5.4 and 31.2% of the patients showed deterioration patterns, and between 0.6 and 8.8% showed improvement patterns in these tests over time. Patients showing better cognitive profiles according to RCISRB (worsening in zero to two cognitive measures) showed better premorbid, clinical and functional profiles than patients showing deterioration patterns in more than three tests. When combining RCISRB and CSC values, we found that less than 10% of patients showed improvement or deterioration patterns in executive function and attention measures. These results support the view that cognitive impairments are stable over the first 2 years of illness, but also that the analysis of individual trajectories could help to identify a subgroup of patients with particular phenotypes, who may require specific interventions.


Assuntos
Atenção/fisiologia , Disfunção Cognitiva/fisiopatologia , Progressão da Doença , Função Executiva/fisiologia , Transtornos Psicóticos/fisiopatologia , Adolescente , Adulto , Disfunção Cognitiva/etiologia , Feminino , Seguimentos , Humanos , Masculino , Testes Neuropsicológicos , Transtornos Psicóticos/complicações , Adulto Jovem
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