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1.
Clin Immunol ; 248: 109251, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36740002

RESUMO

Aging is a complex biological process in which many organs are pathologically affected. We previously reported that aged C57BL/6J had increased lacrimal gland (LG) lymphoid infiltrates that suggest ectopic lymphoid structures. However, these ectopic lymphoid structures have not been fully investigated. Using C57BL/6J mice of different ages, we analyzed the transcriptome of aged murine LGs and characterized the B and T cell populations. Age-related changes in the LG include increased differentially expressed genes associated with B and T cell activation, germinal center formation, and infiltration by marginal zone-like B cells. We also identified an age-related increase in B1+ cells and CD19+B220+ cells. B220+CD19+ cells were GL7+ (germinal center-like) and marginal zone-like and progressively increased with age. There was an upregulation of transcripts related to T follicular helper cells, and the number of these cells also increased as mice aged. Compared to a mouse model of Sjögren syndrome, aged LGs have similar transcriptome responses but also unique ones. And lastly, the ectopic lymphoid structures in aged LGs are not exclusive to a specific mouse background as aged diverse outbred mice also have immune infiltration. Altogether, this study identifies a profound change in the immune landscape of aged LGs where B cells become predominant. Further studies are necessary to investigate the specific function of these B cells during the aged LGs.


Assuntos
Aparelho Lacrimal , Síndrome de Sjogren , Camundongos , Animais , Camundongos Endogâmicos C57BL , Linfócitos B , Tecido Linfoide
2.
Hum Brain Mapp ; 44(5): 2039-2049, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36661404

RESUMO

Cross-modal plasticity in blind individuals has been reported over the past decades showing that nonvisual information is carried and processed by "visual" brain structures. However, despite multiple efforts, the structural underpinnings of cross-modal plasticity in congenitally blind individuals remain unclear. We mapped thalamocortical connectivity and assessed the integrity of white matter of 10 congenitally blind individuals and 10 sighted controls. We hypothesized an aberrant thalamocortical pattern of connectivity taking place in the absence of visual stimuli from birth as a potential mechanism of cross-modal plasticity. In addition to the impaired microstructure of visual white matter bundles, we observed structural connectivity changes between the thalamus and occipital and temporal cortices. Specifically, the thalamic territory dedicated to connections with the occipital cortex was smaller and displayed weaker connectivity in congenitally blind individuals, whereas those connecting with the temporal cortex showed greater volume and increased connectivity. The abnormal pattern of thalamocortical connectivity included the lateral and medial geniculate nuclei and the pulvinar nucleus. For the first time in humans, a remapping of structural thalamocortical connections involving both unimodal and multimodal thalamic nuclei has been demonstrated, shedding light on the possible mechanisms of cross-modal plasticity in humans. The present findings may help understand the functional adaptations commonly observed in congenitally blind individuals.


Assuntos
Cegueira , Lobo Occipital , Humanos , Cegueira/diagnóstico por imagem , Tálamo/diagnóstico por imagem , Lobo Temporal , Corpos Geniculados
3.
Scand J Med Sci Sports ; 33(12): 2524-2533, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37642219

RESUMO

The neurophysiological mechanisms underlying muscle force control for different wrist postures still need to be better understood. To further elucidate these mechanisms, the present study aimed to investigate the effects of wrist posture on the corticospinal excitability by transcranial magnetic stimulation (TMS) of extrinsic (flexor [FCR] and extensor carpi radialis [ECR]) and intrinsic (flexor pollicis brevis (FPB)) muscles at rest and during a submaximal handgrip strength task. Fourteen subjects (24.06 ± 2.28 years) without neurological or motor disorders were included. We assessed how the wrist posture (neutral: 0°; flexed: +45°; extended: -45°) affects maximal handgrip strength (HGSmax ) and the motor evoked potentials (MEP) amplitudes during rest and active muscle contractions. HGSmax was higher at 0° (133%) than at -45° (93.6%; p < 0.001) and +45° (73.9%; p < 0.001). MEP amplitudes were higher for the FCR at +45° (83.6%) than at -45° (45.2%; p = 0.019) and at +45° (156%; p < 0.001) and 0° (146%; p = 0.014) than at -45° (106%) at rest and active condition, respectively. Regarding the ECR, the MEP amplitudes were higher at -45° (113%) than at +45° (60.8%; p < 0.001) and 0° (72.6%; p = 0.008), and at -45° (138%) than +45° (96.7%; p = 0.007) also at rest and active conditions, respectively. In contrast, the FPB did not reveal any difference among wrist postures and conditions. Although extrinsic and intrinsic hand muscles exhibit overlapping cortical representations and partially share the same innervation, they can be modulated differently depending on the biomechanical constraints.


Assuntos
Força da Mão , Músculo Esquelético , Humanos , Eletromiografia , Força da Mão/fisiologia , Músculo Esquelético/fisiologia , Punho/fisiologia , Extremidade Superior , Contração Muscular/fisiologia , Potencial Evocado Motor/fisiologia , Estimulação Magnética Transcraniana
4.
Am J Pathol ; 191(2): 294-308, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33159886

RESUMO

Inflammation and oxidative stress accompany aging. This study investigated the interplay between oxidative stress and inflammation in the lacrimal gland. C57BL/6 mice were used at 2 to 3, 12, and 24 months of age. Nuclear factor erythroid derived-2-related factor 2 (Nrf2)-/- and corresponding wild-type mice were used at 2 to 3 and 12 to 13 months of age. A separate group of 15.5 to 17 months of age C57BL/6 mice received a diet containing an Nrf2 inducer (Oltipraz) for 8 weeks. Aged C57BL/6 lacrimal glands showed significantly greater lymphocytic infiltration, higher levels of MHC II, IFN-γ, IL-1ß, TNF-α, and cathepsin S (Ctss) mRNA transcripts, and greater nitrotyrosine and 4-hydroxynonenal protein. Young Nrf2-/- mice showed an increase in IL-1ß, IFN-γ, MHC II, and Ctss mRNA transcripts compared with young wild-type mice and greater age-related changes at 12 to 13 months of age. Oltipraz diet significantly decreased nitrotyrosine and 4-hydroxynonenal and decreased the expression of IL-1ß and TNF-α mRNA transcripts, while decreasing the frequency of CD45+CD4+ cells in lacrimal glands and significantly increasing conjunctival goblet cell density compared with a standard diet. The findings provide novel insight into the development of chronic, low-grade inflammation and oxidative stress in age-related dry eye. New therapies targeting oxidative stress pathways will be valuable in treating age-related dry eye.


Assuntos
Envelhecimento/patologia , Síndromes do Olho Seco/patologia , Aparelho Lacrimal/patologia , Estresse Oxidativo/fisiologia , Envelhecimento/metabolismo , Animais , Síndromes do Olho Seco/imunologia , Síndromes do Olho Seco/metabolismo , Feminino , Inflamação , Aparelho Lacrimal/imunologia , Aparelho Lacrimal/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pirazinas/farmacologia , Tionas/farmacologia , Tiofenos/farmacologia
5.
Environ Res ; 204(Pt D): 112354, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34767824

RESUMO

Contamination with current-use pesticides is frequently mentioned as a key factor in global amphibian declines although a limited number of studies have examined the mixture of pesticides accumulated by free-living frogs. This study examined the presence of 46 different pesticide residues in the muscle and kidney tissues of two frog species living in close association with row crops in the Pampa region of Argentina: The terrestrial Leptodactylus latinasus and the semi-aquatic Leptodactylus latrans. A total of 20 different pesticides were identified in frog tissues; chlorpyrifos-methyl, pirimiphos-methyl and acetochlor being the most frequently detected molecules. Overall, one or more pesticide residues (up to 12 in a single frog) were detected in 40-57 % of L. latrans. L. latinasus was found to present more pesticide detections than L. latrans. Interestingly, frog sampled in a natural reserve where no pesticides are applied presented an equivalent frequency of detections as frogs living near a crop. In L. latrans, the calculation of a pesticide toxicity index (PTI) permitted to highlight the existence of a strong positive correlation between PTI and liver GSH contents of females whereas, in males, PTI was negatively correlated with the perimeter of testicular seminiferous tubules. Males also presented near significant negative correlations between PTI and both body condition and the scaled fat index. These results indicate that frogs inhabiting agricultural regions are exposed to a complex and diffuse contamination by pesticide mixtures which is likely responsible for a number of biological effects that may be relevant at the population level.


Assuntos
Resíduos de Praguicidas , Praguicidas , Poluentes Químicos da Água , Agricultura , Animais , Anuros , Feminino , Masculino , Praguicidas/análise , Praguicidas/toxicidade , Poluentes Químicos da Água/análise
6.
Allergol Immunopathol (Madr) ; 50(4): 129-136, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35789412

RESUMO

INTRODUCTION: Common variable immunodeficiency (CVID) is the most prevalent symptomatic humoral deficiency; however, its heterogeneous presentation makes the diagnosis difficult. The present study is aimed to verify the CVID diagnostic criteria as established by the European Society for Immunodeficiencies in 42 CVID patients from our outpatient clinic. METHODS: Information was collected from their medical records and when needed, lymphocyte subpopulations in peripheral blood (PB) were performed by flow cytometry. RESULTS: All the patients fulfilled the clinical working definition for CVID and showed decreased serum IgG and IgA at diagnosis. Over two-thirds of the patients had decreased memory B cell percentages. However, the remaining patients exhibited other quantitative B cell defects in PB. Evaluation of vaccination responses was only found in 13 records and 69% were not responsive. None of the patients were subjected to vaccination studies to both, T-cell dependent and independent antigens. The two required tests to evaluate T cell responses were performed in 84.2% of the patients and reported normal. Without the support of third-party payers, only 34.2% of our patients would have completed the required evaluations. CONCLUSIONS: Further efforts are needed to speed up CVID diagnosis in low-resourced settings, increasing the availability of the required resources and optimizing the healthcare supply chain.


Assuntos
Imunodeficiência de Variável Comum , Linfócitos B , Imunodeficiência de Variável Comum/diagnóstico , Citometria de Fluxo , Humanos , Subpopulações de Linfócitos , Linfócitos T
7.
Mol Microbiol ; 113(6): 1240-1254, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32068313

RESUMO

The elucidation of the molecular mechanisms of secretion through bacterial protein secretion systems is impeded by a shortage of assays to quantitatively assess secretion kinetics. Also the analysis of the biological role of these secretion systems as well as the identification of inhibitors targeting these systems would greatly benefit from the availability of a simple, quick and quantitative assay to monitor principle secretion and injection into host cells. Here, we present a versatile solution to this need, utilizing the small and very bright NanoLuc luciferase to assess the function of the type III secretion system encoded by Salmonella pathogenicity island 1. Type III secretion substrate-NanoLuc fusions are readily secreted into the culture supernatant, where they can be quantified by luminometry after removal of bacteria. The NanoLuc-based secretion assay features a very high signal-to-noise ratio and sensitivity down to the nanolitre scale. The assay enables monitoring of secretion kinetics and is adaptable to a high throughput screening format in 384-well microplates. We further developed a split NanoLuc-based assay that enables the real-time monitoring of type III secretion-dependent injection of effector-HiBiT fusions into host cells stably expressing the complementing NanoLuc-LgBiT.


Assuntos
Proteínas de Bactérias/metabolismo , Medições Luminescentes/métodos , Sistemas de Secreção Tipo III/metabolismo , Ensaios de Triagem em Larga Escala/métodos , Luciferases , Transporte Proteico , Salmonella/genética , Salmonella/metabolismo
8.
Blood ; 134(18): 1510-1516, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31501153

RESUMO

Dysregulated immune responses are essential underlying causes of a plethora of pathologies including cancer, autoimmunity, and immunodeficiency. We here investigated 4 patients from unrelated families presenting with immunodeficiency, autoimmunity, and malignancy. We identified 4 distinct homozygous mutations in TNFRSF9 encoding the tumor necrosis factor receptor superfamily member CD137/4-1BB, leading to reduced, or loss of, protein expression. Lymphocytic responses crucial for immune surveillance, including activation, proliferation, and differentiation, were impaired. Genetic reconstitution of CD137 reversed these defects. CD137 deficiency is a novel inborn error of human immunity characterized by lymphocytic defects with early-onset Epstein-Barr virus (EBV)-associated lymphoma. Our findings elucidate a functional role and relevance of CD137 in human immune homeostasis and antitumor responses.


Assuntos
Doenças Autoimunes/genética , Síndromes de Imunodeficiência/genética , Linfoma/genética , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/genética , Doenças Autoimunes/imunologia , Feminino , Predisposição Genética para Doença , Humanos , Síndromes de Imunodeficiência/imunologia , Linfoma/imunologia , Masculino , Linhagem , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/deficiência
9.
Neurocase ; 27(2): 169-177, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33779507

RESUMO

The present study aims at the cerebellum's role in prediction mechanisms triggered by action observation. Five cerebellar patients and six age-paired control subjects were asked to estimate the occluded end point position of the shoulder's trajectories in Sit-to-Stand (STS) or Back-to-Sit (BTS) conditions, following or not biological rules. Contrarily to the control group, the prediction accuracy of the end point position in cerebellar patients did not depend on biological rules. Interestingly, both groups presented similar results when estimating the vanishing position of the target. Taken together, these results suggest that cerebellar damage affectsthe capacity of predicting upcoming actions by observation.


Assuntos
Cerebelo , Movimento , Humanos , Movimento (Física)
10.
J Chem Phys ; 154(7): 074704, 2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33607881

RESUMO

A detailed analysis of the electronic structure of three different electrochemical interfaces as a function of the chemical potential (µ) is performed using the grand canonical density functional theory in the joint density functional theory formulation. Changes in the average number of electrons and the density of states are also described. The evaluation of the global softness, which measures the tendency of the system to gain or lose electrons, is straightforward under this formalism. The observed behavior of these quantities depends on the electronic nature of the electrochemical interfaces.

11.
Neural Plast ; 2021: 6649135, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33688339

RESUMO

Predicting upcoming sensorimotor events means creating forward estimates of the body and the surrounding world. This ability is a fundamental aspect of skilled motor behavior and requires an accurate and constantly updated representation of the body and the environment. To test whether these prediction mechanisms could be affected by a peripheral injury, we employed an action observation and electroencephalogram (EEG) paradigm to assess the occurrence of prediction markers in anticipation of observed sensorimotor events in healthy and brachial plexus injury (BPI) participants. Nine healthy subjects and six BPI patients watched a series of video clips showing an actor's hand and a colored ball in an egocentric perspective. The color of the ball indicated whether the hand would grasp it (hand movement), or the ball would roll toward the hand and touch it (ball movement), or no event would occur (no movement). In healthy participants, we expected to find distinct electroencephalographic activation patterns (EEG signatures) specific to the prediction of the occurrence of each of these situations. Cluster analysis from EEG signals recorded from electrodes placed over the sensorimotor cortex of control participants showed that predicting either an upcoming hand movement or the occurrence of a tactile event yielded specific neural signatures. In BPI participants, the EEG signals from the sensorimotor cortex contralateral to the dominant hand in the hand movement condition were different compared to the other conditions. Furthermore, there were no differences between ball movement and no movement conditions in the sensorimotor cortex contralateral to the dominant hand, suggesting that BPI blurred specifically the ability to predict upcoming tactile events for the dominant hand. These results highlight the role of the sensorimotor cortex in creating estimates of both actions and tactile interactions in the space around the body and suggest plastic effects on prediction coding following peripheral sensorimotor loss.


Assuntos
Mãos/fisiologia , Movimento/fisiologia , Córtex Sensório-Motor/fisiologia , Percepção Espacial/fisiologia , Tato/fisiologia , Adulto , Mapeamento Encefálico/métodos , Eletroencefalografia/métodos , Feminino , Força da Mão/fisiologia , Humanos , Masculino , Percepção do Tato/fisiologia , Adulto Jovem
12.
Mol Microbiol ; 112(3): 918-931, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31183905

RESUMO

Type III secretion injectisomes are essential virulence factors for many pathogenic bacteria by mediating the transport of effector proteins into eukaryotic host cells. The secretion conduit of injectisomes is formed by a helical assembly of three hydrophobic proteins (SctR, SctS and SctT), an inner rod (SctI) and a needle filament (SctF). SctI is thought to play a role in switching between the secretion of different substrate classes and assembly of the inner rod has been implicated in regulating the length of the needle filament. While high-resolution structures of the hydrophobic components and of the needle filament have been solved, little is known about the structure and the assembly of the inner rod, which impedes the deeper assessment of its function. Here we show by exhaustive in vivo photocrosslinking that SctI engages in extensive interactions with SctR and SctT throughout its entire length. Our data imply that the inner rod serves as an adapter between the export apparatus and the needle filament by forming one helical turn. We show that assembly of the inner rod does not play a role in needle length control nor in substrate specificity switching. Instead, our findings imply that inner rod assembly must precede assembly of the needle filament.


Assuntos
Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Salmonella typhimurium/metabolismo , Sistemas de Secreção Tipo III/química , Sistemas de Secreção Tipo III/metabolismo , Proteínas de Bactérias/genética , Humanos , Infecções por Salmonella/microbiologia , Salmonella typhimurium/química , Salmonella typhimurium/genética , Salmonella typhimurium/patogenicidade , Sistemas de Secreção Tipo III/genética , Virulência
13.
Allergol Immunopathol (Madr) ; 48(1): 8-17, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31883622

RESUMO

INTRODUCTION AND OBJECTIVES: LRBA deficiency is caused by loss of LRBA protein expression, due to either homozygous or compounds heterozygous mutations in LRBA. LRBA deficiency has been shown to affect vesicular trafficking and autophagy. To date, LRBA has been observed in the cytosol, Golgi apparatus and some lysosomes in LPS-stimulated murine macrophages. The objectives of the present study were to study the LRBA localization in organelles involved in vesicular traffic, phagocytosis, and autophagy in mononuclear phagocytes (MP). MATERIALS AND METHODS: We analyzed LRBA colocalization with different endosomes markets using confocal microscopy in MP. We used the autophagy inhibitors to determine the role of LRBA in formation, maturation or degradation of the autophagosome. RESULTS: LRBA intracellular trafficking depends on the activity of the GTPase ADP ribosylation factor-1 (ARF) in MP. LRBA was identified in early, late endosomes but did not colocalize strongly with lysosomal markers. Although LRBA appears not to be recruited during the phagocytic cargo uptake, it greatly colocalized with the microtubule-associated protein 1A/1B-light chain 3 (LC3) under a steady state and this decreased after the induction of autophagy flux. Although the use of inhibitors of lysosome fusion did not restore the LRBA/LC3 colocalization, inhibitors of either early to late endosomes trafficking or PI3K pathway did. CONCLUSIONS: Taken together, our results show that LRBA is located in endomembrane system vesicles, mainly in the early and late endosomes. Although LRBA appears not to be involved in the phagocytic uptake, it is recruited in the early steps of the autophagy flux.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Endossomos/metabolismo , Membranas Intracelulares/metabolismo , Fatores de Ribosilação do ADP/antagonistas & inibidores , Fatores de Ribosilação do ADP/metabolismo , Autofagia/efeitos dos fármacos , Brefeldina A/farmacologia , Endossomos/efeitos dos fármacos , Humanos , Membranas Intracelulares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Microscopia Confocal , Proteínas Associadas aos Microtúbulos/metabolismo , Fagócitos/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia
14.
Int J Mol Sci ; 21(23)2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33255287

RESUMO

Dry eye disease (DED), one of the most prevalent conditions among the elderly, is a chronic inflammatory disorder that disrupts tear film stability and causes ocular surface damage. Aged C57BL/6J mice spontaneously develop DED. Rapamycin is a potent immunosuppressant that prolongs the lifespan of several species. Here, we compared the effects of daily instillation of eyedrops containing rapamycin or empty micelles for three months on the aged mice. Tear cytokine/chemokine profile showed a pronounced increase in vascular endothelial cell growth factor-A (VEGF-A) and a trend towards decreased concentration of Interferon gamma (IFN)-γ in rapamycin-treated groups. A significant decrease in inflammatory markers in the lacrimal gland was also evident (IFN-γ, IL-12, CIITA and Ctss); this was accompanied by slightly diminished Unc-51 Like Autophagy Activating Kinase 1 (ULK1) transcripts. In the lacrimal gland and draining lymph nodes, we also observed a significant increase in the CD45+CD4+Foxp3+ cells in the rapamycin-treated mice. More importantly, rapamycin eyedrops increased conjunctival goblet cell density and area compared to the empty micelles. Taken together, evidence from these studies indicates that topical rapamycin has therapeutic efficacy for age-associated ocular surface inflammation and goblet cell loss and opens the venue for new investigations on its role in the aging process of the eye.


Assuntos
Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Síndromes do Olho Seco/tratamento farmacológico , Inflamação/tratamento farmacológico , Interferon gama/genética , Fator A de Crescimento do Endotélio Vascular/genética , Envelhecimento/efeitos dos fármacos , Animais , Antígenos CD4/genética , Linhagem da Célula/efeitos dos fármacos , Túnica Conjuntiva/efeitos dos fármacos , Túnica Conjuntiva/patologia , Córnea , Modelos Animais de Doenças , Síndromes do Olho Seco/genética , Síndromes do Olho Seco/patologia , Fatores de Transcrição Forkhead/genética , Células Caliciformes/efeitos dos fármacos , Humanos , Inflamação/genética , Inflamação/patologia , Antígenos Comuns de Leucócito/genética , Camundongos , Soluções Oftálmicas/farmacologia , Sirolimo/farmacologia , Lágrimas/efeitos dos fármacos , Lágrimas/metabolismo
15.
Genes Immun ; 20(1): 39-45, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29305595

RESUMO

Polymorphic variants p.66L>R/H (g.7081T>G/A; rs10127939) and p.176F>V (g.10872T>G; rs396991) in FCGR3A (CD16A) have been associated with defects in cytotoxic function of natural killer (NK) cells in humans. Genotyping of these variants in genomic DNA has been ambiguous because of high degree of homology between FCGR3A and FCGR3B. We designed a strategy to genotype these polymorphisms and to evaluate their effects on NK cells' cytotoxic activity. One hundred and fifteen individuals from different geographical regions of Colombia were included. Specific primers were designed to amplify FCGR3A exons 4 and 5 encompassing g.7081T>G/A and g.10872T>G by long-range and nested polymerase chain reaction and sequencing. The binding of different monoclonal antibodies to CD16A and NK antibody-dependent cellular cytotoxicity (ADCC) were evaluated. We demonstrate that amplifying and sequencing FCGR3A allows genotyping of g.7081T>G/A and g.10872T>G without interference from FCGR3B. Allele frequencies in our population were as follows: 7081T = 0.895, 7081G = 0.065, 7081 A = 0.039, 10872T = 0.673, and 10872G = 0.326. We also observed linkage disequilibrium between variants 7081T and 10872G. Interestingly, 176FF variant affected the reactivity of MEM154 monoclonal antibody against CD16A, but it did not affect ADCC. Our studies aimed to determine whether clinical association exists between these polymorphisms and NK cell function defects in patients with compatible phenotypes.


Assuntos
Frequência do Gene , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único , Receptores de IgG/genética , Anticorpos Monoclonais/imunologia , Citotoxicidade Imunológica , Técnicas de Genotipagem/métodos , Humanos , Células Matadoras Naturais/imunologia , Desequilíbrio de Ligação , Receptores de IgG/imunologia , Análise de Sequência de DNA/métodos
16.
J Musculoskelet Neuronal Interact ; 19(3): 317-325, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31475939

RESUMO

Spasticity is a sensorimotor disorder widely recognized as one of the features that contribute to patients' disability. Transcutaneous electric neural stimulation (TENS/SES) has been adopted in spasticity rehabilitation as an alternative to pharmacological agents. Although previous studies have reported clinical benefits of TENS/SES in relieving spasticity, there is no clarity on how and whether this therapeutic modality affects specific neural circuitries. Thus, this systematic review aimed to verify the efficacy of TENS/SES in the control of spasticity and its consequences in spinal and corticospinal excitability. This study was carried out according to PRISMA recommendations using SCOPUS, PubMed, BVS, Google Scholar and BASE databases screening, which provided 483 references. Six additional records were found from other sources. All these records were submitted to a filtering process following the eligibility criteria, and 44 studies were selected for further analysis. Ten were replicas. Consequently, 34 studies were read in full with the aim of checking their eligibility criterion, which resulted in 10 manuscripts for qualitative synthesis. Even though they evaluated the effects of TENS/SES both at the spinal and/or corticospinal levels, the electrophysiological results seem to be inconsistent, corroborating the lack of agreement between them and with clinical outcomes.


Assuntos
Espasticidade Muscular/terapia , Estimulação Elétrica Nervosa Transcutânea/métodos , Humanos , Resultado do Tratamento
17.
Prev Chronic Dis ; 16: E128, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31538568

RESUMO

PURPOSE AND OBJECTIVES: We conducted a pilot study to assess the degree to which an intervention led by community health advisors (CHAs) to promote cancer screening was delivered as intended and to estimate the potential effect of the intervention on receipt of screening. In contrast to previous studies and to maximize its potential public health impact, the intervention targeted 4 screening tests and only participants who were not up to date with screening guidelines for at least 1 cancer. Because CHAs had to both determine baseline adherence and provide counseling on 4 screening tests, the protocol was complex. Complex protocols can reduce implementation fidelity. INTERVENTION APPROACH: In partnership with health ministries at 9 African American churches in South Los Angeles, we conducted a 1-group pretest-posttest pilot study to assess the feasibility of implementing the intervention. CHAs recruited and obtained consent from church members aged 50 to 75 years; assessed adherence to national screening guidelines for breast, cervical, colorectal, and prostate cancer; and provided evidence-based strategies (one-on-one counseling, print materials, reminder calls) to encourage screening for tests that were overdue. EVALUATION METHODS: We assessed implementation fidelity by reviewing baseline screening assessments and counseling scripts completed by CHAs. We estimated potential effect of the intervention on receipt of screening by using data from 3-month follow-up surveys, conducted by the research team, of participants who were nonadherent at baseline. RESULTS: From June 2016 to June 2018, 44 CHAs conducted baseline assessments of 775 participants, of whom 338 (44%) were nonadherent to national guidelines for 1 or more cancer screening tests. CHAs provided counseling to most nonadherent participants. At follow-up, about one-third of participants reported that they had discussed cancer screening with their provider and a smaller proportion reported receipt of a screening test; 13% of men and 25% of women reported receipt of colorectal cancer screening. IMPLICATIONS FOR PUBLIC HEALTH: This study demonstrates that with training and ongoing technical assistance, CHAs at African American health ministries can implement complex research protocols with good fidelity.


Assuntos
Negro ou Afro-Americano , Detecção Precoce de Câncer , Educação em Saúde/métodos , Promoção da Saúde/métodos , Neoplasias/diagnóstico , Agentes Comunitários de Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Los Angeles/epidemiologia , Neoplasias/epidemiologia , Projetos Piloto , Avaliação de Programas e Projetos de Saúde , Saúde Pública
18.
Exp Brain Res ; 235(2): 437-446, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27770165

RESUMO

Loss of vision is well known to affect postural control in blind subjects. This effect has classically been framed in terms of deficit or compensation depending on whether body sway increases or decreases in comparison with that of sighted subjects with the eyes open. However, studies have shown that postural responses can be modulated by the context and that changes in postural sway may not necessarily mean a worsened or improved postural control. The goal of our study was to test whether balance is affected by the context in blind subjects. Additional to the quantification of center of pressure (COP) displacement, measurements of body motion (COG) and the correspondent net neuromuscular response (COP-COG) were evaluated in anterior-posterior and medial-lateral directions. Thirty-eight completely blind and thirty-two sighted subjects participated of this study. The volunteers were asked to stand barefoot on a force platform for 60 s in two different conditions: feet apart and feet together. Sighted participants performed the tests with both the eyes open and eyes closed. Results showed that the COP-COG displacements in the blind group were greater than those of the sighted group with eyes open in almost all conditions tested, but not in eyes closed condition. However, the COP and COG results confirmed that the postural responses were context dependent. Together these results suggest that total visual loss does not just lead to a balance deficit or compensation, but to a specific postural signature that might imply in enhancing COP, COG and/or COP-COG in specific postural conditions.


Assuntos
Cegueira/complicações , Equilíbrio Postural/fisiologia , Postura/fisiologia , Transtornos de Sensação/etiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Movimento (Física) , Orientação/fisiologia , Pressão , Estatísticas não Paramétricas , Adulto Jovem
19.
BMC Bioinformatics ; 17(Suppl 15): 441, 2016 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-28185567

RESUMO

BACKGROUND: Deep mining of healthcare data has provided maps of comorbidity relationships between diseases. In parallel, integrative multi-omics investigations have generated high-resolution molecular maps of putative relevance for understanding disease initiation and progression. Yet, it is unclear how to advance an observation of comorbidity relations (one disease to others) to a molecular understanding of the driver processes and associated biomarkers. RESULTS: Since Chronic Obstructive Pulmonary disease (COPD) has emerged as a central hub in temporal comorbidity networks, we developed a systematic integrative data-driven framework to identify shared disease-associated genes and pathways, as a proxy for the underlying generative mechanisms inducing comorbidity. We integrated records from approximately 13 M patients from the Medicare database with disease-gene maps that we derived from several resources including a semantic-derived knowledge-base. Using rank-based statistics we not only recovered known comorbidities but also discovered a novel association between COPD and digestive diseases. Furthermore, our analysis provides the first set of COPD co-morbidity candidate biomarkers, including IL15, TNF and JUP, and characterizes their association to aging and life-style conditions, such as smoking and physical activity. CONCLUSIONS: The developed framework provides novel insights in COPD and especially COPD co-morbidity associated mechanisms. The methodology could be used to discover and decipher the molecular underpinning of other comorbidity relationships and furthermore, allow the identification of candidate co-morbidity biomarkers.


Assuntos
Doença Pulmonar Obstrutiva Crônica/patologia , Envelhecimento , Biomarcadores/metabolismo , Mapeamento Cromossômico , Análise por Conglomerados , Comorbidade , Bases de Dados Factuais , Progressão da Doença , Humanos , Estilo de Vida , Análise de Componente Principal , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/genética , Risco , Fumar
20.
Exp Brain Res ; 234(9): 2585-94, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27161552

RESUMO

It has been suggested that tactile perception becomes less acute during movement to optimize motor control and to prevent an overload of afferent information generated during action. This empirical phenomenon, known as "tactile gating effect," has been associated with mechanisms of sensory feedback prediction. However, less attention has been given to the tactile attenuation effect during the observation of an action. The aim of this study was to investigate whether and how the observation of a goal-directed action influences tactile perception as during overt action. In a first experiment, we recorded vocal reaction times (RTs) of participants to tactile stimulations during the observation of a reach-to-grasp action. The stimulations were delivered on different body parts that could be either congruent or incongruent with the observed effector (the right hand and the right leg, respectively). The tactile stimulation was contrasted with a no body-related stimulation (an auditory beep). We found increased RTs for tactile congruent stimuli compared to both tactile incongruent and auditory stimuli. This effect was reported only during the observation of the reaching phase, whereas RTs were not modulated during the grasping phase. A tactile two-alternative forced-choice (2AFC) discrimination task was then conducted in order to quantify the changes in tactile sensitivity during the observation of the same goal-directed actions. In agreement with the first experiment, the tactile perceived intensity was reduced only during the reaching phase. These results suggest that tactile processing during action observation relies on a process similar to that occurring during action execution.


Assuntos
Atenção/fisiologia , Desempenho Psicomotor/fisiologia , Percepção do Tato/fisiologia , Adulto , Feminino , Mãos/fisiologia , Força da Mão , Humanos , Masculino , Movimento/fisiologia , Tempo de Reação/fisiologia , Percepção Espacial , Tato/fisiologia , Adulto Jovem
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