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1.
Nat Immunol ; 20(6): 677-686, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31110312

RESUMO

Consumption of a high-energy Western diet triggers mild adaptive ß cell proliferation to compensate for peripheral insulin resistance; however, the underlying molecular mechanism remains unclear. In the present study we show that the toll-like receptors TLR2 and TLR4 inhibited the diet-induced replication of ß cells in mice and humans. The combined, but not the individual, loss of TLR2 and TLR4 increased the replication of ß cells, but not that of α cells, leading to enlarged ß cell area and hyperinsulinemia in diet-induced obesity. Loss of TLR2 and TLR4 increased the nuclear abundance of the cell cycle regulators cyclin D2 and Cdk4 in a manner dependent on the signaling mediator Erk. These data reveal a regulatory mechanism controlling the proliferation of ß cells in diet-induced obesity and suggest that selective targeting of the TLR2/TLR4 pathways may reverse ß cell failure in patients with diabetes.


Assuntos
Células Secretoras de Insulina/metabolismo , Obesidade/etiologia , Obesidade/metabolismo , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Animais , Proliferação de Células , Ciclina D2/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Feminino , Humanos , Insulina/sangue , Insulina/metabolismo , Células Secretoras de Insulina/ultraestrutura , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Knockout , Complexos Multiproteicos/metabolismo , Obesidade/tratamento farmacológico , Parabiose , Ligação Proteica , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo
2.
Nicotine Tob Res ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38890771

RESUMO

INTRODUCTIONS: An increasing number of countries are adopting the tobacco endgame goal. High levels of public support can accelerate momentum towards implementing tobacco endgame policies. We aimed to conduct a systematic review of public support for tobacco endgame policies and to examine the geographical distribution of studies, support among key populations (adolescents and young adults, people who smoke), and the association between survey design and support. METHODS: We searched Embase, PubMed, Scopus, Web of Science, and Google Scholar for studies published from 2013 onwards. Google was used to search the grey literature. The reference lists of included articles were hand-searched. Studies were included if they reported the proportions of people supporting one or more endgame policies. Risk of bias was assessed using the JBI checklist for prevalence studies. RESULTS: Forty-seven articles were included. Aotearoa/New Zealand and the United States were the countries with the most studies (n=11, respectively). Three-level meta-analyses showed the highest support for mandating a very low nicotine content in tobacco products (76%, 95% CI 61-87%). Meta-regressions were performed to assess the associations of population subgroup and survey design with support levels. The level of support was lower among people who smoke compared to the general population (ß range: -1.59 to -0.51). Support for some policies was lower when neutral or don't know response options were included. CONCLUSIONS: Public support for most tobacco endgame policies was high. IMPLICATIONS: Assessing public support can assist with progressing tobacco endgame policies. Policies that are widely supported by the public may be more politically feasible to implement. Qualitative studies and trial studies can further inform communication and implementation strategies for tobacco endgame policies.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38165595

RESUMO

BACKGROUND: Core lexicon (CL) analysis is a time efficient and possibly reliable measure that captures discourse production abilities. For people with aphasia, CL scores have demonstrated correlations with aphasia severity, as well as other discourse and linguistic measures. It was also found to be clinician-friendly and clinically sensitive enough to capture longitudinal changes in aphasia. To our knowledge, CL has never been investigated in individuals with neurologically progressive disease. AIMS: As a preliminary investigation, we sought to investigate (1) whether CL scores correlate with dementia severity, (2) whether CL scores correlate with measures of discourse quality, and (3) whether CL scores correlate with other measures of lexical/semantic access. METHODS & PROCEDURES: Twelve participants with a cognitive impairment associated with dementia of the Alzheimer's type (DAT) completed several measures of language and cognitive ability, as well as provide a language sample from the wordless picture book, Picnic. RESULTS & CONCLUSION: Results are informative, as they provide insight into characteristics of CL and provide support for potential use of CL in individuals with neurologically progressive disease. The results indicated that CL scores do correlate with dementia severity and several measures of language ability, indicating they may provide a useful measure of language abilities in DAT, but more research is needed. WHAT THIS PAPER ADDS: What is already known on the subject Core lexicon (CL) analysis is an assessment measure of discourse ability, most closely related to informativeness or productivity, used in aphasiology that is easier to use and less time consuming than previous measures of informativeness, such as correct information units or type-token ratio (TTR). For people with aphasia, CL analysis correlates with aphasia severity, measures of informativeness, as well as other measures of discourse quality. It has also been shown to be faster and more reliable between scorers than other informativeness measures. What this study adds Core lexicon analysis is a new simple and online method for assessing the informativeness of a discourse sample without the need to record or transcribe the language sample. CL is receiving a lot of attention in aphasia, correlating with everything from aphasia severity to measures of productivity and lexical access, as well as measures of informativeness. Unfortunately, no one has investigated CL analysis in dementia. The study demonstrates the first evidence that CL analysis may be a useful measure for determining dementia severity and language quality in people with dementia. What are the clinical implications of this work? Core lexicon analysis may provide clinicians and researchers with an easy method for assessing the discourse of people with a cognitive impairment associated with dementia of the Alzheimer's type. This will improve initial assessment, as well as improve ongoing language assessment that may provide clues into their functional ability to communicate effectively.

4.
Clin Lab ; 68(5)2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35536090

RESUMO

BACKGROUND: Serology testing is useful to determine the past infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We evaluated the comparative performance of a newly developed neutralizing antibody test (R-FIND SARS-CoV-2 Neutralizing Antibody ELISA, SG Medical, Seoul, Korea) and a rapid fluorescence immunoassay (FREND™ COVID-19 SP, NanoEntek, Hwaseong, Korea) for the detection of SARS-CoV-2 spike protein antibody. They were compared with cPass™ SARS-CoV-2 Neutralization Antibody Detection Kit (Genscript Biotech, Piscataway, NJ, USA) and ADVIA Centaur SARS-CoV-2 Total (COV2T) (Siemens Healthineers, Erlangen, Germany). Forty COVID-19 samples and 80 negative samples were collected after nucleic acid tests. RESULTS: The positive percent agreement (%) of the kit in samples from 6 - 7 days, 8 - 14 days, and 15 - 45 days after symptom onset were as follows: R-FIND (83.3, 76.9, 95.2), cPass (83.3, 69.2, 90.5), FREND (66.6, 84.6, 100), and COV2T (66.6, 69.2, 76.2). The negative percent agreement (%) was 100, 97.5, 92.5, and 100 for R-FIND, cPass, FREND, and COV2T. The total agreement rate between the neutralizing antibody kits (R-FIND and cPass) was 96.7%. FREND showed high agreement with two neutralizing antibody kits (96.7% for R-FIND and 93.3% for cPass). CONCLUSIONS: R-FIND Neutralizing Antibody and FREND COVID-19 SP showed comparable detecting ability to commercial tests.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/diagnóstico , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoensaio , Sensibilidade e Especificidade , Glicoproteína da Espícula de Coronavírus
5.
Proc Natl Acad Sci U S A ; 116(38): 19090-19097, 2019 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-31481626

RESUMO

Aberrant T cell development is a pivotal risk factor for autoimmune disease; however, the underlying molecular mechanism of T cell overactivation is poorly understood. Here, we identified NF-κB-inducing kinase (NIK) and IkB kinase α (IKKα) in thymic epithelial cells (TECs) as essential regulators of T cell development. Mouse TEC-specific ablation of either NIK or IKKα resulted in severe T cell-mediated inflammation, injury, and fibrosis in the liver and lung, leading to premature death within 18 d of age. NIK or IKKα deficiency abrogated medullary TEC development, and led to breakdown of central tolerance, production of autoreactive T cells, and fatal autoimmune destruction in the liver and lung. TEC-specific ablation of NIK or IKKα also impaired thymic T cell development from the double-negative through the double-positive stages and inhibited peripheral B cell development. These results unravel a hitherto unrecognized essential role of TEC-intrinsic NIK and IKKα pathways in autoimmunity and T cell-instigated chronic liver and lung diseases.


Assuntos
Autoimunidade/imunologia , Quinase I-kappa B/fisiologia , Inflamação/imunologia , Fígado/imunologia , Pulmão/imunologia , Proteínas Serina-Treonina Quinases/fisiologia , Timo/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Diferenciação Celular , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Homeostase , Inflamação/metabolismo , Inflamação/patologia , Fígado/metabolismo , Fígado/patologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Timo/metabolismo , Timo/patologia , Quinase Induzida por NF-kappaB
6.
Int J Mol Sci ; 23(13)2022 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-35806412

RESUMO

The abuse or misuse of antibiotics has caused the emergence of extensively drug-resistant (XDR) bacteria, rendering most antibiotics ineffective and increasing the mortality rate of patients with bacteremia or sepsis. Antimicrobial peptides (AMPs) are proposed to overcome this problem; however, many AMPs have attenuated antimicrobial activities with hemolytic toxicity in blood. Recently, AMPR-11 and its optimized derivative, AMPR-22, were reported to be potential candidates for the treatment of sepsis with a broad spectrum of antimicrobial activity and low hemolytic toxicity. Here, we performed molecular dynamics (MD) simulations to clarify the mechanism of lower hemolytic toxicity and higher efficacy of AMPR-22 at an atomic level. We found four polar residues in AMPR-11 bound to a model mimicking the bacterial inner/outer membranes preferentially over eukaryotic plasma membrane. AMPR-22 whose polar residues were replaced by lysine showed a 2-fold enhanced binding affinity to the bacterial membrane by interacting with bacterial specific lipids (lipid A or cardiolipin) via hydrogen bonds. The MD simulations were confirmed experimentally in models that partially mimic bacteremia conditions in vitro and ex vivo. The present study demonstrates why AMPR-22 showed low hemolytic toxicity and this approach using an MD simulation would be helpful in the development of AMPs.


Assuntos
Bacteriemia , Proteínas de Membrana , Proteínas Mitocondriais , Simulação de Dinâmica Molecular , Antibacterianos/química , Antibacterianos/farmacologia , Peptídeos Antimicrobianos/química , Peptídeos Antimicrobianos/farmacologia , Bacteriemia/metabolismo , Bactérias , Membrana Celular/metabolismo , Hemólise , Humanos , Proteínas de Membrana/química , Proteínas de Membrana/farmacologia , Testes de Sensibilidade Microbiana , Proteínas Mitocondriais/química , Proteínas Mitocondriais/farmacologia
7.
Dement Geriatr Cogn Disord ; 50(5): 446-453, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34814138

RESUMO

PURPOSE: We aimed to investigate: (1) the clinical, diagnostic value of a written discourse task, and (2) the relationship between executive functions and written discourse within the spectrum of individuals with mild cognitive impairment (MCI). METHOD: To determine whether written discourse performance predicts clinical course among individuals with MCI, we retrospectively classified individuals with MCI as converters (N = 26) who were later diagnosed with dementia or as a stable MCI group (N = 45). We quantified core word measures from written discourse samples obtained from the Cookie Theft picture description task. RESULT: Written discourse measures differentiated converters from the stable MCI group. Converters produced a fewer number of core words than the stable MCI group. A measure of executive function significantly predicted performance on the production of core words in written discourse for the converters. In a multivariable regression, production of core words remained the only explanatory variable closely associated with the progression to dementia in MCI. CONCLUSION: Written discourse tasks can predict the likelihood of MCI progressing to dementia, independently of recall and an executive function measure. Correlational results suggest that written discourse performance was associated with executive function as measured by the Trail Making Test. Our findings emphasize the usefulness of including written discourse tasks in language assessment batteries targeting preclinical dementia populations.


Assuntos
Disfunção Cognitiva , Demência , Redação , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Demência/diagnóstico , Demência/psicologia , Progressão da Doença , Função Executiva , Humanos , Idioma , Testes Neuropsicológicos , Estudos Retrospectivos
8.
Int J Med Sci ; 18(16): 3738-3743, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790047

RESUMO

Background: Coronary artery disease (CAD) is an important issue in public health. Previous studies have shown that the ratio of fat to muscle mass is a significant predictor of metabolic disease, and it is known to be associated with atherosclerosis. In this study, we evaluated the association between the fat-to-muscle ratio (FMR) and CAD in healthy adults. Methods: A total of 617 participants without diabetes mellitus, hypertension, known CAD, or stroke who visited the Health Promotion Center from 2009 to 2018 were included in this study. Computed tomography imaging and bioelectrical impedance analysis were used to ascertain the coronary artery calcium (CAC) score, degree of CAD, and FMR. Results: Univariate logistic regression analysis showed that old age, male sex, smoking history, creatinine, aspartate aminotransferase, gamma-glutamyl transferase, uric acid, total cholesterol, and low-density lipoprotein cholesterol were significantly associated with CAC. After adjusting for potential confounding covariates, the presence of CAC was independently associated with FMR (OR, 1.014; 95% CI, 1.002-1.026; p = 0.019. The association was maintained even after adjusting for body mass index and waist circumference (odds ratio, 1.019; 95% confidence interval, 1.004 -1.034; P = 0.012). Conclusion: In this study, a high FMR was significantly associated with CAC. A large-scale prospective study on the association with FMR and cardiovascular diseases is necessary to confirm this relationship.


Assuntos
Tecido Adiposo/patologia , Doença da Artéria Coronariana/diagnóstico , Músculos/patologia , Tecido Adiposo/fisiologia , Adulto , Idoso , Doenças Assintomáticas , Biomarcadores/análise , Composição Corporal/fisiologia , Estudos de Casos e Controles , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/patologia , Feminino , Indicadores Básicos de Saúde , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , República da Coreia , Estudos Retrospectivos , Fatores de Risco
9.
Int J Lang Commun Disord ; 56(1): 6-19, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32909656

RESUMO

BACKGROUND: Although discourse-level assessments contribute to predicting real-world performance in persons with aphasia (PWA), the use of discourse measures is uncommon in clinical settings due to resource-heavy procedures. Moreover, assessing function word use in discourse requires the arduous procedure of defining grammatical categories for each word in language transcripts. AIMS: The purpose of this exploratory study was twofold: (1) to develop core function word lists as a clinician-friendly means of evaluating function word use in discourse; and (2) to examine the ability of the core function word measure to differentiate PWA from cognitively healthy adults and persons with fluent aphasia from non-fluent aphasia. METHODS & PROCEDURES: The 25 most commonly used function words (core function words) were extracted from narrative language samples from 470 cognitively healthy adults, which were divided into seven age groups (20s, 30s, 40s, 50s, 60s, 70s and 80s). The percent agreement of core function words for 11 PWA (fluent aphasia = 5; non-fluent aphasia = 6) and 11 age- and education-matched controls were then calculated. Percent agreement for the core function words produced was compared between the controls and the PWA group, and between participants with fluent aphasia and non-fluent aphasia. OUTCOMES & RESULTS: The results indicated that PWA produced fewer core function words from the lists than the control group, and that core function word use was strongly correlated with aphasia severity. Persons with non-fluent aphasia produced fewer core function words than those with fluent aphasia, although this could be a confound of aphasia classification from the use of the Western Aphasia Battery (WAB)-Revised. CONCLUSIONS & IMPLICATIONS: Core function word lists consisting of a limited number of items for quantifying function word use in discourse remain in a nascent stage of development. However, the findings are consistent with previous studies analysing the total production of function words in language samples produced by PWA. Therefore, core function words may potentially serve as a clinician-friendly manner of quantifying function words produced in discourse. What this paper adds What is already known on the subject Function word analysis in discourse requires arduous processes of identifying the error production and grammatical category of function words in discourse. Previous studies have demonstrated that core lexicon measures are an efficient, simple means of quantifying discourse in PWA. However, function words have never been considered for generating an independent core lexicon list. What this paper adds to existing knowledge As an exploratory study, we focused primarily on developing a clinician-friendly measure to evaluate function word production in discourse, motivated by the idea of an adaptation strategy within the core lexicon framework. Our findings demonstrated that by using a simple scoring system that the core lexicon measure provides, we differentiated the control group from the PWA group, and persons with fluent aphasia from persons with non-fluent aphasia. Additionally, we found significant correlations between function word production and aphasia severity determined by WAB Aphasia Quotient (AQ). What are the potential or actual clinical implications of this work? The results add empirical evidence for the utility of core function word lists for quantifying function word usage in discourse in PWA. Counting the presence and absence of function words in discourse will allow clinicians to avoid labour-intensive preparatory work, and to obtain useful diagnostic information in a less time-consuming way.


Assuntos
Afasia , Afasia/diagnóstico , Afasia de Wernicke , Humanos , Idioma , Narração
10.
Malar J ; 19(1): 163, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32321547

RESUMO

BACKGROUND: Insecticide-treated net (ITN) use is the core intervention among the strategies against malaria in sub-Saharan Africa (SSA) and the percentage of ITN ownership has increased from 47% in 2010 to 72% in 2017 across countries in SSA. Regardless of this massive expansion of ITN distribution, considerable gap between ownership and use of ITNs has been reported. Using data from more than 100,000 households in Central and East Africa (CEA) countries, the main aim of this study was to identify barriers associated with low ITN use and conduct geospatial analyses to estimate numbers and locations of vulnerable children living in areas with high malaria and low ITN use. METHODS: Main sources of data for this study were the Demographic and Health Surveys and Malaria Indicator Surveys conducted in 11 countries in CEA. Logistic regression models for each country were built to assess the association between ITN ownership or ITN use and several socioeconomic and demographic variables. A density map of children under 5 living in areas at high-risk of malaria and low ITN use was generated to estimate the number of children who are living in these high malaria burden areas. RESULTS: Results obtained suggest that factors such as the number of members in the household, total number of children in the household, education and place of residence can be key factors linked to the use of ITN for protecting children against malaria in CEA. Results from the spatiotemporal analyses found that although total rates of ownership and use of ITNs across CEA have increased up to 70% and 48%, respectively, a large proportion of children under 5 (19,780,678; 23% of total number of children) still lives in high-risk malaria areas with low use of ITNs. CONCLUSION: The results indicate that despite substantial progress in the distribution of ITNs in CEA, with about 70% of the households having an ITN, several socioeconomic factors have compromised the effectiveness of this control intervention against malaria, and only about 48% of the households protect their children under 5 with ITNs. Increasing the effective ITN use by targeting these factors and the areas where vulnerable children reside can be a core strategy meant to reducing malaria transmission.


Assuntos
Mosquiteiros Tratados com Inseticida/estatística & dados numéricos , Malária/prevenção & controle , Fatores Socioeconômicos , África Central , África Oriental , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Controle de Mosquitos , Propriedade/estatística & dados numéricos , Análise Espaço-Temporal
11.
Semin Speech Lang ; 41(1): 20-31, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31869846

RESUMO

Evidence suggests that discourse-level assessment in aphasia should be implemented within clinical settings. However, existing discourse measures that are time and labor intensive in process prevent speech-language pathologists from applying such measures to their clinical practices. This article provides an overview of a lexicon-based analysis (core lexicon measure) that recently was developed and investigated for clinical usability. A new approach to core lexicon measures provides a simple scoring method with short instructions, which may be practical and time efficient for assessment and management of persons with aphasia. The article concludes with suggestions for clinical application and implementation.


Assuntos
Afasia/terapia , Patologia da Fala e Linguagem/educação , Humanos , Fonoterapia , Vocabulário
12.
Semin Speech Lang ; 41(1): 45-60, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31869848

RESUMO

Core Lexicon (CoreLex) is a relatively new approach assessing lexical use in discourse. CoreLex examines the specific lexical items used to tell a story, or how typical lexical items are compared with a normative sample. This method has great potential for clinical utilization because CoreLex measures are fast, easy to administer, and correlate with microlinguistic and macrolinguistic discourse measures. The purpose of this article is to provide clinicians with a centralized resource for currently available CoreLex checklists, including information regarding development, norms, and guidelines for use.


Assuntos
Afasia , Lista de Checagem , Vocabulário , Humanos , Guias de Prática Clínica como Assunto
13.
Clin Infect Dis ; 68(6): 984-992, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30060038

RESUMO

BACKGROUND: An understanding of immune responses against the Middle East respiratory syndrome (MERS) is important for the development of treatments and preventive measures. Here, we investigated the spectrum of immune responses occurring in patients with MERS during the early period of infection. METHODS: We obtained peripheral blood samples from 27 hospitalized patients recruited during the epidemic that occurred in 2015 in South Korea. Plasma cytokines/chemokines and antibodies were quantified. Virus-specific T cells were examined by intracellular cytokine staining after stimulation of peripheral blood mononuclear cells with overlapping peptides spanning whole virus structural proteins. RESULTS: At the acute phase of infection, elevated levels of plasma proinflammatory cytokines/chemokines were detected in proportion to the severity of the disease. Distinctively high frequencies of MERS coronavirus-reactive CD8+ T cells were also observed in patients with severe/moderate illness, whereas antibody and CD4+ T-cell responses were minimally detected at this stage. At the convalescent phase, disease severity-dependent antibody responses emerged and antigen-reactive cells were identified in both T-cell subsets. These T cells belonged to the T-helper 1 or type 1 cytotoxic T cell subtypes. While CD8+ T cells responded preferentially to the viral S protein compared with E/M/N proteins, especially at the acute stage, slightly more CD4+ T cells recognized E/M/N proteins compared with S protein at the convalescent phase. CONCLUSIONS: Our findings show an association between the early CD8+ T-cell response and the severity of the infection, and also provide basic information that may help to prepare effective control strategies for MERS in humans.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Interações Hospedeiro-Patógeno/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Adulto , Idoso , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Infecções por Coronavirus/epidemiologia , Citocinas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Avaliação de Resultados da Assistência ao Paciente , República da Coreia , Subpopulações de Linfócitos T/imunologia , Adulto Jovem
14.
Wound Repair Regen ; 27(4): 345-359, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30835922

RESUMO

Proliferative and migratory abilities of fibroblasts are essential for wound healing at the skin surface. Cytoplasmic linker-associated protein-2 (CLASP2) was originally found to interact with cytoplasmic linker protein (CLIP)-170. CLASP2 plays an important role in microtubule stabilization and the microtubule-stabilizing activity of CLASP2 depends on its interactions with end binding (EB)-1 and CLIP-170. Although the microtubule-stabilizing role of CLASP2 is well established, the effects of CLASP2 on the migration and proliferation of fibroblasts remain unclear in the context of wound healing. Therefore, we tested the utilization of CLASP2 as a directly applied protein drug to improve wound healing by promoting the migration of effector cells, including skin fibroblasts, to the site of repair or injury using an in vivo excisional wound mouse model and in vitro Hs27 skin fibroblast model. Epidermal growth factor, which is a recognized contributor to cell proliferation and migration, was used as positive control. In vitro and in vivo, CLASP2 treatment significantly enhanced cell migration and accelerated wound closure. Furthermore, in vivo, the CLASP2-treated animal group displayed enhanced epidermal repair and collagen deposition. Next, we studied the mechanism of CLASP2 for wound healing. Increasing the abundance of intracellular free CLASP2 in skin fibroblasts by supplying exogenous CLASP2 seemed to stabilize microtubules through an interaction between CLASP2 and CLIP-170, as well as EB1. Exogenous CLASP2 also showed direct binding with IQGAP1, increasing both cyclic adenosine monophosphate activity and phosphorylation of glycogen synthase kinase 3ß, which in turn reinstated the binding between free CLASP2 and IQGAP1. In summary, exogenous CLASP2 increased Hs27 skin fibroblast migration by interacting with IQGAP1 and other cytoskeletal linker proteins, such as CLIP-170 and EB1. Our results strongly suggest that CLASP2 can be developed in wound healing drugs for skin repair and/or regenerating cosmetic products.


Assuntos
Fibroblastos/efeitos dos fármacos , Proteínas Associadas aos Microtúbulos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Ferimentos e Lesões/patologia , Animais , Movimento Celular , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Células Cultivadas , Modelos Animais de Doenças , Fibroblastos/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Cicatrização/fisiologia
15.
Int J Lang Commun Disord ; 54(1): 62-78, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30426603

RESUMO

BACKGROUND: Discourse analysis procedures are time consuming and impractical in a clinical setting. Critical to clinicians are simple and informative discourse measures that require minimal time and labour to complete. Many studies, however, have overlooked difficulties that clinicians face. We recently developed core lexicon lists for nouns, verbs, adjectives and adverbs for two narrative discourse tasks with healthy control groups. Core lexicon lists consist of important lexical items required to produce coherently meaningful discourse in response to discourse tasks. Measuring core lexicon is useful for quantifying word retrieval impairments at the discourse level in clinical populations. AIMS: To apply an age-based core lexicon list for nouns, verbs, adjectives and adverbs for the wordless picture books Good Dog Carl (1985) and Picnic (1984) and to determine how well the lists measured linguistic impairments in persons with aphasia (PWA). MATERIALS & METHODS: Lemma forms were extracted from 470 control participants who were divided into seven age groups. Twenty-five core lexicons were identified for four word classes (nouns, verbs, adjectives and adverbs) among the seven age groups. The nouns, verbs, adjectives and adverbs for each PWA (N = 11) were then compared with the core lexicon for their respective age group. Per cent agreement was computed by comparing the number of total items within each list to the number of items that PWA produced. A Spearman's correlation coefficient was computed between the WAB-R AQ and the per cent agreement for each word type for PWA. OUTCOMES & RESULTS: The percentage of agreement for each word type among the age cohorts ranged between 56% and 96%. Of the four word types, core verbs significantly correlated with the WAB AQs for both discourse tasks. A post-hoc analysis found significant differences between fluent and non-fluent aphasia for core verbs. CONCLUSIONS & IMPLICATIONS: Core lexicon analysis appears to be a practical way to capture impairments in word retrieval at the discourse level. Core verbs may be a better indicator to understand holistic language performances for PWA. Use of the core lexicon checklist can serve as an option to reconcile ecological validity with clinical usability.


Assuntos
Afasia/diagnóstico , Cognição , Idioma , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Afasia/psicologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Narração , Vocabulário , Adulto Jovem
16.
J Phys Ther Sci ; 30(2): 252-257, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29545688

RESUMO

[Purpose] The purpose of the present study was to compare the postural sway of healthy adults standing on different types of balance pads. [Subjects and Methods] Nine healthy adults participated in this study. Postural body sway was measured while participants were standing on four different types of balance pads: Balance-pad Elite (BE), Aero-Step XL (AS), Dynair Ballkissen Senso (DBS), and Dynair Ballkissen XXL Meditation and Yoga (DBMY). A Wii Balance Board interfaced with Balancia software was used to measure postural body sway. [Results] In the sway velocity, sway path length, and sway area, no significant differences were found between baseline conditions (participants were standing on the floor with no balance pad) and the use of the BE or AS. However, significant increases in all parameters were found comparing baseline conditions to the use of either Dynair balance pad. Furthermore, the use of either Dynair balance pad significantly increased postural sway compared to both the BE and the AS. [Conclusion] These findings suggest that the DBS and DBMY balance pads may serve as superior tools for providing unstable condition for balance training than the BE and the AS balance pads.

17.
Eur J Nutr ; 56(5): 1993-2002, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27743130

RESUMO

PURPOSE: Alcoholic liver disease or non-alcoholic fatty liver disease/non-alcoholic steatohepatitis are well-known risk factors for liver fibrosis or cirrhosis and hepatocellular carcinoma; it is a major global health concern, but there are few effective and safe management options. Therefore, we aimed to investigate the effects of fermented garlic extracts (FGEs) on hepatic function in adults with mild hepatic dysfunction without underlying hepatic disease. METHODS: In this double-blind, randomized, placebo-controlled study, seventy-five adults with elevated serum gamma-glutamyl transpeptidase (GGT) levels were included in a FGE-administered group (n = 36) or a placebo group (n = 39), and received either two sachets/day containing FGEs or placebo over a 12-week period. Primary endpoint was the change in serum GGT levels. Data were analysed using a generalized linear mixed effects model. RESULTS: Significant group × time interactions for serum levels of GGT (F = 3.98, P = 0.022) and alanine aminotransferase (ALT; F = 3.28, P = 0.043) were observed with an improvement in levels of GGT (P = 0.066) and ALT (P = 0.014) in the FGE group compared to that reported for the placebo group at the 12-week visits. There was no intergroup difference in the prevalence of adverse events. CONCLUSIONS: Intake of FGEs improved serum GGT and ALT levels in adults with mildly elevated serum GGT level without reported adverse side effects. FGEs might be effective and safe management options for mild hepatic dysfunction.


Assuntos
Fermentação , Alho , Fígado/fisiologia , gama-Glutamiltransferase/sangue , Adulto , Idoso , Alanina Transaminase/sangue , Antioxidantes/farmacologia , Povo Asiático , Aspartato Aminotransferases/sangue , Colesterol/sangue , Dieta , Método Duplo-Cego , Determinação de Ponto Final , Exercício Físico , Feminino , Manipulação de Alimentos , Humanos , Hepatopatias/sangue , Hepatopatias/prevenção & controle , Masculino , Pessoa de Meia-Idade , Tamanho da Amostra , Fatores Socioeconômicos , Triglicerídeos/sangue
18.
Proc Natl Acad Sci U S A ; 111(18): 6732-7, 2014 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-24706784

RESUMO

Light-activated, ion-pumping rhodopsins are broadly distributed among many different bacteria and archaea inhabiting the photic zone of aquatic environments. Bacterial proton- or sodium-translocating rhodopsins can convert light energy into a chemiosmotic force that can be converted into cellular biochemical energy, and thus represent a widespread alternative form of photoheterotrophy. Here we report that the genome of the marine flavobacterium Nonlabens marinus S1-08(T) encodes three different types of rhodopsins: Nonlabens marinus rhodopsin 1 (NM-R1), Nonlabens marinus rhodopsin 2 (NM-R2), and Nonlabens marinus rhodopsin 3 (NM-R3). Our functional analysis demonstrated that NM-R1 and NM-R2 are light-driven outward-translocating H(+) and Na(+) pumps, respectively. Functional analyses further revealed that the light-activated NM-R3 rhodopsin pumps Cl(-) ions into the cell, representing the first chloride-pumping rhodopsin uncovered in a marine bacterium. Phylogenetic analysis revealed that NM-R3 belongs to a distinct phylogenetic lineage quite distant from archaeal inward Cl(-)-pumping rhodopsins like halorhodopsin, suggesting that different types of chloride-pumping rhodopsins have evolved independently within marine bacterial lineages. Taken together, our data suggest that similar to haloarchaea, a considerable variety of rhodopsin types with different ion specificities have evolved in marine bacteria, with individual marine strains containing as many as three functionally different rhodopsins.


Assuntos
Cloretos/metabolismo , Flavobacteriaceae/metabolismo , Bombas de Íon/classificação , Rodopsina/metabolismo , Evolução Molecular , Flavobacteriaceae/genética , Flavobacteriaceae/efeitos da radiação , Genoma Bacteriano , Bombas de Íon/genética , Bombas de Íon/efeitos da radiação , Luz , Dados de Sequência Molecular , Filogenia , Rodopsina/genética
19.
Int J Food Sci Nutr ; 68(1): 90-96, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27537342

RESUMO

The present study investigated the associations between serum vitamin D levels and carotid intima-media thickness (CIMT), carotid plaque and atherosclerosis in 71 Korean adults. CIMT and the presence of carotid plaque were assessed with a high-resolution B-mode ultrasound system, and carotid atherosclerosis was defined as a mean CIMT value >0.9 mm or the presence of carotid plaque. A vitamin D deficiency was associated with the presence of carotid plaque (adjusted odds ratio [aOR]: 9.25, 95% confidence interval [CI]: 1.52-56.3; p = 0.016). As serum vitamin D levels increased, the presence of high-risk carotid plaque decreased (aOR: 0.84, 95%CI: 0.72-0.99; p = 0.039). Serum vitamin D levels was negatively associated with carotid atherosclerosis (aOR: 0.86, 95%CI: 0.76-0.97; p = 0.018). Further studies are needed to investigate whether vitamin D supplementation would be effective for the prevention of atherosclerosis and cardiovascular diseases.


Assuntos
Aterosclerose/etiologia , Estenose das Carótidas/etiologia , Estado Nutricional , Deficiência de Vitamina D/fisiopatologia , 25-Hidroxivitamina D 2/sangue , Aterosclerose/diagnóstico por imagem , Aterosclerose/epidemiologia , Aterosclerose/etnologia , Biomarcadores/sangue , Calcifediol/sangue , Espessura Intima-Media Carotídea , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/epidemiologia , Estenose das Carótidas/etnologia , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Estado Nutricional/etnologia , Prevalência , República da Coreia/epidemiologia , Fatores de Risco , Autorrelato , Índice de Gravidade de Doença , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/etnologia
20.
Semin Speech Lang ; 38(1): 40-51, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28201836

RESUMO

Evidence suggests that persons with aphasia (PWAs) present with working memory impairments that affect a variety of language tasks. Most of these studies have focused on the phonological loop component of working memory and little attention has been paid to the episodic buffer component. The episodic buffer, as a limited capacity, multimodal system that binds and integrates information from the phonological loop, visuospatial sketchpad, and long-term memory would likely be involved in discourse processing. The purposes of this article were to (1) review discourse level deficits associated with aphasia, (2) describe how a deficit at the level of the episodic buffer could cause such deficits, (3) to review discourse treatment approaches for PWAs, and (4) present preliminary results from a novel discourse treatment study for PWAs.


Assuntos
Afasia/psicologia , Afasia/reabilitação , Afasia/terapia , Transtornos da Memória/diagnóstico , Transtornos da Memória/psicologia , Transtornos da Memória/terapia , Memória de Curto Prazo , Percepção da Fala , Comportamento Verbal , Idoso , Idoso de 80 Anos ou mais , Afasia/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fonética , Retenção Psicológica
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