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1.
Am J Speech Lang Pathol ; 33(2): 952-968, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38232175

RESUMO

PURPOSE: The purpose of this study was to calibrate an item set for a new version of the Communicative Participation Item Bank (CPIB) specifically for use with gender-diverse clients. This new version contains a new item stem as well as other minor wording changes from the original CPIB in order to be acceptable to gender-diverse respondents. METHOD: Survey data on 47 candidate items were collected from 434 transgender individuals: 219 assigned female at birth (AFAB) and 215 assigned male at birth (AMAB). Item response theory analyses included evaluation of unidimensionality, local dependence, fit to a graded response model, and differential item functioning (DIF) between AFAB and AMAB respondents. RESULTS: The original set of 47 items was unidimensional, but 16 items were removed due to local dependence, resulting in a final item bank of 31 items. There was no evidence of DIF between AFAB and AMAB participants. Reliability of the full item bank is good (i.e., > 0.8) between T scores of 20 and 76 and high (i.e., > 0.9) between T scores of 20 and 68. The short form had good reliability (i.e., > 0.8) between T scores of 24 and 64. CONCLUSIONS: The Communicative Participation Item Bank-Gender-Diverse (CPIB-GD) version provides a new option for person-reported outcome measurement with gender-diverse clients. Clinicians are cautioned to use only the new CPIB-GD with gender-diverse clients, and not the original CPIB due to unacceptable wording in the original version for this population. The original CPIB remains valid and appropriate for the populations for which it was developed. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24993309.


Assuntos
Comunicação , Recém-Nascido , Humanos , Masculino , Feminino , Calibragem , Reprodutibilidade dos Testes , Inquéritos e Questionários , Psicometria
2.
Int J Lang Commun Disord ; 59(2): 808-827, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37855252

RESUMO

BACKGROUND: The Communicative Participation Item Bank (CPIB) is a patient-reported outcome measure (PROM) designed to measure the extent of interference, or difficulty, experienced by adults with communication disorders participating in their day-to-day communication activities. To date, there is limited evidence regarding sensitivity of the CPIB for capturing change with intervention in people with Parkinson's disease (PwPD). AIMS: The purpose of this study was to examine the following measurement properties of the CPIB in PwPD who received community-based, standard care, speech-language therapy focusing on motor speech concerns: Change over time between treatment and observation groups, comparison to patient-defined ideal and satisfactory targets, comparison of static short form to computerised adaptive testing (CAT), comparison of self to proxy-rated scores, and comparison to other common PROMs. METHODS AND PROCEDURES: Forty-six PwPD (20 treatment/26 observation) completed data collection upon enrolment (pre-treatment) and 6 months later. In addition to the CPIB, PROMs included the Voice Handicap Index 10-item short form (VHI-10), PROMIS Global Health-Related Quality of Life, Levels of Speech Usage, self-rated speech severity, and Patient Health Questionnaire-9 (PHQ-9). Participants also engaged in qualitative interviews. Forty-four family members completed proxy CPIB ratings. OUTCOMES AND RESULTS: There were no significant differences between treatment and observation groups on the CPIB pre-treatment, but there were significant differences post-treatment. The differences appeared to be largely due to significant gains in the treatment group. No participants reached their ideal CPIB target, and few reached their satisfactory target. Static CPIB short form and CAT scores were not significantly different, with an average of five CAT items administered per participant. Overall group similarities between patient and proxy scores may have obscured wide variability across individual patient-proxy pairs. Associations between CPIB and VHI-10, health-related quality of life, self-reported speech severity, and depression ranged from weak to moderate. CONCLUSIONS AND IMPLICATIONS: The CPIB appears to be sensitive to capturing change with intervention, and similar results are obtained with the static short form and CAT formats. One clinical caution is that even with gains observed in the treatment group, no participants obtained their ideal communicative participation goals, and few obtained a satisfactory level of communicative participation. Thus, while current interventions are beneficial, they may not meet the full range of clients' communication needs. While responding to the CPIB through a proxy rater may be feasible, caution is warranted due to concerns about maintaining the autonomy of PwPD. WHAT THIS PAPER ADDS: What is already known on this subject The communication disorders associated with Parkinson's disease (PD) can have a negative impact on quality of life and life participation as measured by patient (or person)-reported outcome measures (PROMs). The Communicative Participation Item Bank (CPIB) is one PROM available to use with adults with communication disorders. However, little is known about whether the CPIB captures changes in communicative participation as a result of standard care treatment for people with Parkinson's disease (PwPD). Use of computerised adaptive testing (CAT), proxy report and comparison to targeted participation outcomes have not been explored. What this study adds to existing knowledge As a result of this study, we know that the CPIB captured differences between treatment and observation groups after community-based, standard care speech therapy intervention focusing on motor speech production in PwPD. Static short form and CAT scores did not differ significantly, so the CAT option provides better efficiency requiring, on average, five items to administer compared to the 10-item short form. Proxy and PwPD scores did not differ as a group, but wide variability was noted. What are the potential or actual clinical implications of this work? The CPIB may be a clinically sensitive instrument for capturing changes in communicative participation after treatment. No participants met their ideal CPIB target, and few reached their satisfactory target, suggesting that while current interventions contribute to gains in communicative participation, there are still unmet needs that may call for support and interventions addressing the more complex array of factors affecting communicative participation outcomes for PwPD.


Assuntos
Transtornos da Comunicação , Doença de Parkinson , Adulto , Humanos , Fonoterapia , Fala , Terapia da Linguagem , Doença de Parkinson/complicações , Qualidade de Vida , Comunicação
3.
Int J Speech Lang Pathol ; : 1-15, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37907084

RESUMO

PURPOSE: To understand the communicative participation experiences of transgender people through a qualitative inquiry, and to address similarities and differences in experiences across genders. METHOD: This study was a secondary analysis of interview data gathered for modifying the Communicative Participation Item Bank for use with transgender populations. Fourteen transgender participants attended individual qualitative interviews. During the interview, participants shared their communication experiences in various situations and the availability of social supports related to communication. Qualitative content analysis was used to develop themes and subthemes from the data. RESULT: Three themes emerged from the data: the participants' priorities for comfort, safety, and authenticity; the use of an internal "checklist" to optimise their communication; and changes in attitudes towards communication over time. Across themes, participants shared core communication experiences regardless of gender identities. CONCLUSION: The findings support prior research on voice-related communication experiences of transgender people. A key finding is the notion that communication success is influenced by sociocultural contexts and the physical environment beyond their communication presentation. To achieve targeted comfort and satisfaction in communication, healthcare professionals need to consider the transgender client's communication contexts, and incorporate a life-participation approach to gender-affirming voice and communication training.

4.
Front Endocrinol (Lausanne) ; 14: 1085799, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36843578

RESUMO

Obesity is a complex disease characterized by excessive fat accumulation which is caused by genetic, environmental and other factors. In recent years, there has been an increase in the morbidity, disability rate,and mortality due to obesity, making it great threat to people's health and lives, and increasing public health care expenses. Evidence from previous studies show that weight loss can significantly reduce the risk of obesity-related complications and chronic diseases. Diet control, moderate exercise, behavior modification programs, bariatric surgery and prescription drug treatment are the major interventions used to help people lose weight. Among them, anti-obesity drugs have high compliance rates and cause noticeable short-term effects in reducing obese levels. However, given the safety or effectiveness concerns of anti-obesity drugs, many of the currently used drugs have limited clinical use. Glucagon-like peptide-1 receptor (GLP-1R) agonists are a group of drugs that targets incretin hormone action, and its receptors are widely distributed in nerves, islets, heart, lung, skin, and other organs. Several animal experiments and clinical trials have demonstrated that GLP-1R agonists are more effective in treating or preventing obesity. Therefore, GLP-1R agonists are promising agents for the treatment of obese individuals. This review describes evidence from previous research on the effects of GLP-1R agonists on obesity. We anticipate that this review will generate data that will help biomedical researchers or clinical workers develop obesity treatments based on GLP-1R agonists.


Assuntos
Fármacos Antiobesidade , Receptor do Peptídeo Semelhante ao Glucagon 1 , Animais , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Obesidade/etiologia , Incretinas , Fármacos Antiobesidade/uso terapêutico , Redução de Peso
5.
J Commun Disord ; 102: 106312, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36791644

RESUMO

INTRODUCTION: The Communicative Participation Item Bank (CPIB) is a person-reported outcome measure designed for adults with communication disorders. The CPIB has not been validated for use with clients seeking gender-affirming communication care. The purpose of this study was to determine modifications needed to the CPIB for it to be appropriate for transgender respondents. METHODS: Individual qualitative cognitive interviews were conducted with 14 transgender adults (seven assigned male at birth, six assigned female at birth, one intersex / assigned female at birth). As participants completed the CPIB, they were asked to 'think out loud' to share their reactions to the items, reasons for their item responses, and any recommendations for changing the CPIB. Interviews were recorded, transcribed, and analyzed to identify common and salient trends in participants' feedback. RESULTS: The most salient change participants required was in the CPIB item stem. The original stem ("Does your condition interfere with….") is inappropriate for transgender clients because referring to being transgender as a 'condition' is unacceptable. A new stem ("How difficult is it for you to ….") was acceptable to participants. The original CPIB uses the phrase 'family and friends' to refer to safe and comfortable communication partners. Participants in this study reported that this does not reflect the experiences of many transgender people who are not accepted by their biological families. The recommended alternate wording is "people who know you well." The items reflected situations that were relevant to participants, and wording was acceptable with few exceptions. Participants suggested they would have responded to the CPIB items differently earlier in their transition, with their scores improving over time. CONCLUSIONS: The original CPIB questionnaire should not be used with transgender clients due to unacceptable wording. The modified items generated from this study require psychometric calibration for a new CPIB version for clients seeking gender-affirming communication care.


Assuntos
Transtornos da Comunicação , Pessoas Transgênero , Adulto , Recém-Nascido , Humanos , Masculino , Feminino , Retroalimentação , Comunicação , Inquéritos e Questionários , Pessoas Transgênero/psicologia , Cognição
7.
Clin Rheumatol ; 42(1): 135-143, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36074221

RESUMO

OBJECTIVES: To explore the value of plasmablasts in predicting disease relapse in IgG4-related diseases (IgG4-RD). METHODS: Treatment-naïve IgG4-RD patients treated with glucocorticoid (GC) monotherapy or leflunomide (LEF) and GC combination therapy diagnosed at the Chinese PLA General Hospital during February 2017 and January 2018 were included in this study. The absolute plasmablast count was measured by using the absolute count tubes with flow cytometry. Patients were categorized into high and low plasmablast level groups by defining the median number of plasmablasts as the cut-off value. The characteristics of the clinical manifestations between the two groups were compared. In addition, the correlation of plasmablast count with other indicators and its clinical value in predicting disease relapse were evaluated. RESULTS: Data of 37 treatment-naïve IgG4-RD patients were analyzed. The median (IQR) absolute count of plasmablasts was 4.0 (2.8-7.5)/µL, which was correlated with the lymphocyte percentage, serum IgG, IgG4, and IgG4/IgG. The baseline absolute count of plasmablasts was an independent risk factor for disease relapse in IgG4-RD patients (HR, 1.199; 95% CI, 1.030-1.396, P = 0.019), and the application of LEF was an independent protective factor (HR, 0.283; 95% CI, 0.106-0.759, p = 0.012). CONCLUSIONS: The present study preliminarily indicated that baseline absolute plasmablast count may independently predict disease relapse in patients with IgG4-RD treated with GC monotherapy or LEF and GC combination therapy. More efforts are still needed to be performed in the future. Key Points • The absolute count of plasmablasts is correlated with the lymphocyte percentage, serum IgG, IgG4 and IgG4/IgG. • The baseline absolute plasmablast count may predict disease relapse in patients with IgG4-RD treated with GC monotherapy or LEF and GC combination therapy. • The application of LEF is an independent protective factor for disease relapse in IgG4-RD.


Assuntos
Doença Relacionada a Imunoglobulina G4 , Humanos , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Plasmócitos , Leflunomida/uso terapêutico , Doença Crônica , Recidiva , Imunoglobulina G
8.
Theranostics ; 12(18): 7775-7787, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36451858

RESUMO

Rationale: The efficacy and mechanism of hydroxyurea in the treatment of atherosclerosis have rarely been reported. The goal of this study was to investigate the efficacy of hydroxyurea in high-fat diet-fed ApoE-/- mice against atherosclerosis and examine the possible mechanism underlying treatment outcomes. Methods: ApoE-/- mice were fed a high-fat diet for 1 month and then administered hydroxyurea by gavage continuously for 2 months. Aortic root hematoxylin-eosin (H&E) staining and oil red O staining were used to verify the efficacy of hydroxyurea; biochemical methods and ELISA were used to detect changes in relevant metabolites in serum. 16S rRNA was used to detect composition changes in the intestinal bacterial community of animals after treatment with hydroxyurea. Metabolomics methods were used to identify fecal metabolites and their changes. Immunohistochemical staining and ELISA were used for the localization and quantification of intestinal NPC1L1. Results: We showed that aortic root HE staining and oil red O staining determined the therapeutic efficacy of hydroxyurea in the treatment of atherosclerosis in high-fat diet-fed ApoE-/- mice. Serological tests verified the ability of hydroxyurea to lower total serum cholesterol and LDL cholesterol. The gut microbiota was significantly altered after HU treatment and was significantly different from that after antiplatelet and statin therapy. Meanwhile, a metabolomic study revealed that metabolites, including stearic acid, palmitic acid and cholesterol, were significantly enriched in mouse feces. Further histological and ELISAs verified that the protein responsible for intestinal absorption of cholesterol in mice, NPC1L1, was significantly reduced after hydroxyurea treatment. Conclusions: In high-fat diet-fed ApoE-/- mice, hydroxyurea effectively treated atherosclerosis, lowered serum cholesterol, modulated the gut microbiota at multiple levels and affected cholesterol absorption by reducing NPC1L1 in small intestinal epithelial cells.


Assuntos
Aterosclerose , Microbioma Gastrointestinal , Camundongos , Animais , Hidroxiureia , Proteína C1 de Niemann-Pick , RNA Ribossômico 16S/genética , Apolipoproteínas E/genética , Aterosclerose/tratamento farmacológico
9.
Ultrason Sonochem ; 86: 106031, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35569439

RESUMO

The effects of different ultrasonic pretreatments (120-600 W, 20 min; 360 W, 10-30 min) on the gel properties of shrimp surimi were investigated. Gel properties and protein functional properties were analysed to clarify the mechanism of action of ultrasound. The gel strength, water holding capacity and surface hydrophobicity of shrimp surimi gel increased initially and then decreased with the increase in ultrasound power or time, but the change in total sulfhydryl content showed the opposite trend, which indicated that proper ultrasound pretreatment could improve the gel properties of shrimp surimi, expand the protein to a greater extent and expose more SH groups and hydrophobic groups. According to scanning electron microscopy observation, ultrasound made shrimp surimi gel form a denser gel network. Fourier transform infrared analysis indicated that the α-helix content in shrimp surimi gel decreased initially and then increased with the increase of in ultrasound power or time, whereas the change in ß-sheet content showed the opposite trend. And the protein was the most stable in 360 W/20 min pretreatment. SDS-PAGE patterns showed that proper ultrasound inhibited the degradation of actin and troponin C. In addition, dynamic rheology illustrated that the G' values of the ultrasonic pretreatment group were higher than that of the control group, indicating that ultrasound could improve the elasticity and stability of shrimp surimi gel. The results suggested that the shrimp surimi gel pretreated by 360 W/20 min ultrasound showed the best gel properties. Furthermore, the correlation between the indexes affecting the properties of the gel was analyzed. This study provides a new technical means to improve the gel properties of shrimp surimi.


Assuntos
Penaeidae , Animais , Géis/química , Interações Hidrofóbicas e Hidrofílicas , Cloreto de Sódio/análise , Cloreto de Sódio na Dieta , Ultrassom
11.
Front Med (Lausanne) ; 8: 678864, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34150809

RESUMO

Background and Purpose: The effect of Iguratimod in the treatment of rheumatoid arthritis was confirmed in past studies. In terms of the mechanism of the effect and clinical application experience, Iguratimod has a potential value in the treatment of spondyloarthritis (SpA). This study evaluated the efficacy and safety of Iguratimod on active SpA. Methods: Subjects with active SpA were enrolled and randomly divided into two groups at a ratio of 1:2 (placebo vs. Iguratimod). On the basis of non-steroidal anti-inflammatory drugs, combined treatment with Iguratimod or placebo, followed by follow-up every 4 weeks for 24 weeks. The primary efficacy endpoint was to evaluate the alleviation rate of ASAS20; the important improvement of ASDAS and the efficacy of spinal mobility, physical function and quality of life at the 24th week. Results: A total of 48 cases in the Iguratimod group and 25 cases in the placebo group were included in the final analysis. On the 24th week, the percentage of responders to ASAS20 (80 vs. 44%) and ASAS40 (56 vs. 20%) treated with Iguratimod were significantly higher than that in the placebo group (P < 0.05). Twelve cases had gastrointestinal discomfort, of which eight were in the Iguratimod group (16.7%, one case withdrew from the study due to diarrhoea) and four were in the placebo group (16.0%). No significant difference was found between the two groups (P < 0.05). Three cases of elevated transaminase were observed in the Iguratimod group and none in the placebo group, with no significant difference (P < 0.05). Conclusion: Iguratimod could significantly reduce the symptoms and signs of patients with active SpA. It could improve the physical function and quality of life of these patients and the overall safety and tolerance are good.

12.
Front Med (Lausanne) ; 8: 680598, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34095182

RESUMO

Aim: To compare the clinical and radiological characteristics of osteomalacia and spondyloarthritis/ankylosing spondylitis (SpA/AS) in order to provide a basis for differential diagnosis. Methods: We carried out a retrospective analysis of patients who were diagnosed with osteomalacia at the First Medical Center of 301 Hospital (Beijing, China) from January 2012 to January 2019. The clinical and radiological data of all patients were collected; at the same time, we selected age- and gender-matched patients with SpA/AS for comparison. Results: We enrolled a total of 76 patients, 38 with osteomalacia, and 38 with SpA/AS. The mean ages of the two groups were, respectively 44.62 ± 14.90 years and 44.85 ± 9.76 years (P > 0.05). Of patients with osteomalacia, 65.79% (n = 25) had previously been misdiagnosed with SpA/AS. In the osteomalacia and SpA/AS groups, there were, respectively 31 and 33 patients with low back pain, 22 and 13 patients with peripheral arthralgia, and 13 and 3 patients with heel pain. Alkaline phosphatase (ALP) level was significantly higher in the osteomalacia than in the SpA/AS group (P < 0.05). Serum phosphorus levels, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, and bone mineral density (BMD) were significantly lower in the osteomalacia group than the SpA/AS group (P < 0.05). Twenty-five patients in the osteomalacia group underwent sacroiliac-joint magnetic-resonance imaging (SIJ-MRI); abnormalities were found in 10 of these patients, seven of whom met the definition for positive SIJ-MRI according to 2009 Assessment of SpondyloArthritis international Society (ASAS) criteria. All seven presented with bilateral sacral involvement. Logistic-regression analysis found that the odds ratio (OR) for bone erosion score was 0.551; the higher this score, the lower the possibility of osteomalacia. Conclusion: Clinical and radiological presentations of patients with osteomalacia could highly simulate those of patients with spondyloarthritis; identifying the differences between these two diseases could effectively decrease the misdiagnosis rate.

13.
Am J Speech Lang Pathol ; 30(3S): 1301-1313, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-33656912

RESUMO

Purpose The purpose of this study was to explore the extent to which communicative participation differs across diagnoses and if there are common predictor variables for communicative participation across diagnoses. Method Survey data on self-report variables including communicative participation were collected from 141 community-dwelling adults with communication disorders due to Parkinson's disease, cerebrovascular accident, spasmodic dysphonia, or vocal fold immobility (VFI). Analysis of covariance was used to determine communicative participation differences between diagnoses, with age, sex, and hearing status as covariates. Sequential entry linear regression was used to examine associations between communicative participation and variables representing a range of psychosocial constructs across diagnoses. Results The VFI group had the least favorable communicative participation differing significantly from Parkinson's disease and spasmodic dysphonia groups. Self-rated speech/voice severity, self-rated effort, mental health, perceived social support, and resilience contributed to variance in communicative participation when pooled across diagnoses. The relationship between communicative participation and the variables of effort and resilience differed significantly when diagnosis was considered. Conclusions The findings suggest that communicative participation restrictions may vary across some diagnoses but not others. People with VFI appear to differ from other diagnosis groups in the extent of participation restrictions. Effort and resilience may play different roles in contributing to communicative participation in different disorders, but constructs such as social support, severity, and mental health appear to have consistent relationships with communicative participation across diagnoses. The findings can help clinicians identify psychosocial factors beyond the impairment that impact clients' communication in daily situations.


Assuntos
Transtornos da Comunicação , Disfonia , Adulto , Comunicação , Transtornos da Comunicação/diagnóstico , Disfonia/diagnóstico , Humanos , Fala , Inquéritos e Questionários
14.
Semin Arthritis Rheum ; 50(6): 1513-1520, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32113839

RESUMO

OBJECTIVES: To evaluate the efficacy and safety of leflunomide (LEF) and glucocorticoids (GCs) combination therapy compared with GCs monotherapy in preventing relapse of IgG4-related disease (IgG4-RD). METHODS: A 12-month, randomized, open-label, controlled trial was conducted at a large academic medical center (ClinicalTrials.gov: NCT02703194). Enrolled patients with active IgG4-RD were randomly allocated to the GCs + LEF (20 mg/day) combination therapy or GCs monotherapy group. All patients received GCs with a predefined taper regimen starting from a dosage of 0.5-0.8 mg/kg/d. The primary outcome was the time to relapse. The secondary outcomes included complete response, remission, GCs dosage, and serum IgG4 level. RESULTS: Sixty-six patients with active IgG4-RD were enrolled (33 patients in each group). The demographic and disease characteristics showed no statistically significant differences between groups. Additionally, the initial GCs dosages were similar (50.00 vs. 50.00 mg/day, P = 0.295). Disease relapses occurred in 6 (18.2%) and 14 (42.4%) patients in the combination therapy group and GCs monotherapy group, respectively (P = 0.032). The combination therapy was significantly superior to GCs monotherapy regarding the primary outcome, the time to relapse (HR, 0.35; 95% confidence interval [CI], 0.13-0.90; P = 0.023), as well as the secondary outcome, the time to complete response (HR, 1.75; 95% CI, 1.01-3.02; P = 0.034). A longer duration of remission was observed in the combination therapy group (7.00 vs. 3.00 months, P = 0.002) and less cumulative dosage of GCs was used (5103.13 vs. 5637.50 mg, P = 0.031). Additionally, a higher proportion of patients in the combination therapy group (54.5%) were able to reach a daily GCs dose of ≤5 mg/day compared with the GCs monotherapy group (18.2%) (P = 0.006). The incidences of adverse events were similar in the 2 groups (P = 0.325). CONCLUSION: LEF in combination with GCs therapy is well-tolerated and significantly superior to GCs monotherapy in preventing the relapse of IgG4-RD. LEF can be used as a steroid-sparing agent in the management of IgG4-RD.


Assuntos
Doença Relacionada a Imunoglobulina G4 , Quimioterapia Combinada , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Leflunomida/uso terapêutico , Recidiva , Resultado do Tratamento
15.
Front Pharmacol ; 11: 581049, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33708107

RESUMO

Traditional herb pair Salvia miltiorrhiza Bunge-Radix Puerariae (DG) owns various biological activities including anti-inflammatory and anti-oxidative stress. Oxidative stress is one high-risk factor for osteoporosis, then effect of DG on osteoporosis and underlying mechanisms was explored both in vivo and in vitro. Firstly, the predication from network pharmacology hinted that DG has the potential for ameliorating osteoporosis. Consistent with predication, DG significantly restored bone loss and deficiency of type II collagen, decreased TRAP and Cathepsin K positive areas in femur. Meanwhile it improved important characteristics of microarchitectural deterioration of tissue, reduced the numbers of NFATc1-positive osteoclast in the vertebra as well as decreased the serum osteoclast-specific cytokine RANKL and OPG release in OVX rats exhibiting its protective effect against osteoporosis. In vitro, DG noticeably decreased osteoclastic-special marker protein expressions of RANK, c-Fos and NFATc1. Furthermore, autophagy pathway p62/LC3B, ROS production and NF-κB were all activated by RANKL stimulation and blocked by DG pretreatment. Moreover, autophagy inhibitors, ROS scavenger, Ca2+ chelator and NF-κB inhibitor remarkably suppressed c-Fos and NFATc1 expressions. Taken together, DG may ameliorate osteoporosis by regulating osteoclast differentiation mediated by autophagy and oxidative stress. This study provided a mechanistic basis for DG treating osteoporosis and offered a safe dose for DG in preventing and improving bone diseases.

16.
Psychopharmacology (Berl) ; 236(11): 3301-3315, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31197433

RESUMO

RATIONALE: The volatile anesthetic isoflurane is suggested to produce a rapid and robust antidepressive effect in preliminary clinical trials. Recently, isoflurane was found to activate the tropomyosin receptor kinase B (TrkB) signaling which is the underlying mechanism of the rapid antidepressant ketamine. OBJECTIVE: Our study investigated the effect of isoflurane anesthesia on chronic unpredictable mild stressed (CUMS) model in mice and verified the role of brain-derived neurotrophic factor (BDNF)/TrkB/ the mammalian target of rapamycin (mTOR) signaling in the antidepressant effect of isoflurane. METHODS: We employed the CUMS model of depression to assess the rapid antidepressant effect of isoflurane by the forced swimming test (FST), the sucrose preference test (SPT), and the novelty suppressed feeding test (NSFT). The protein expression of BDNF and TrkB/protein kinase B (PKB or Akt)/mTOR was determined through Western blot. The dendritic spine density in the hippocampus and medial prefrontal cortex (PFC) was measured by the Golgi staining. RESULTS: A brief burst-suppressing isoflurane anesthesia rapidly reversed the behavioral deficits caused by CUMS procedure, normalized the expression of BDNF and further activated the TrkB signaling pathway in CUMS-induced stressed mice in both prefrontal cortex (PFC) and hippocampus (HC). All of those behavioral and proteomic effects were blocked by K252a, a selective receptor inhibitor of TrkB. Isoflurane significantly promoted the formation of dendritic spines in both medial prefrontal cortex (mPFC), CA1, CA3, and DG of the hippocampus. CONCLUSION: Our study indicates that isoflurane exerts a rapid antidepressant-like effect in CUMS depression animal model, and the activation of BDNF/TrkB signaling pathway plays an indispensable role in the biological and behavioral antidepressant effects of isoflurane. A single exposure to isoflurane could repair synaptic damage caused by chronic stimulation.


Assuntos
Antidepressivos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/metabolismo , Isoflurano/farmacologia , Glicoproteínas de Membrana/metabolismo , Proteínas Tirosina Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Anestésicos Inalatórios/farmacologia , Anestésicos Inalatórios/uso terapêutico , Animais , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Depressão/psicologia , Relação Dose-Resposta a Droga , Isoflurano/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Transdução de Sinais/fisiologia , Estresse Psicológico/metabolismo
17.
Arch Med Sci ; 15(3): 700-705, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31110537

RESUMO

INTRODUCTION: To investigate the effect of dose maintenance, reduction, or discontinuation of the etanercept biosimilar Yisaipu (YSP) on early axial spondyloarthritis (axSpA) patients in remission with YSP 50 mg once weekly (QW). MATERIAL AND METHODS: Patients were enrolled in three groups: full dose (YSP50), half dose (YSP25), and discontinuation (YSP0). Patients were assessed by the same rheumatologist every 8 weeks for 48 weeks. The primary endpoint was the proportion of non-failure patients in each group. If a flare occurred during the study period, the patient resumed YSP 50 mg QW or was switched to another tumor necrosis factor inhibitor. RESULTS: A total of 144 patients were included and each group included 48 patients. The proportion of non-failure patients was significantly greater in the YSP50 group than in the YSP0 group at 48 weeks (91.7% vs. 72.9%, p = 0.032). The difference in the other two comparisons was not statistically significant (YSP50 vs. YSP25 group, p = 0.522; YSP25 vs. YSP0 group, p = 0.132). The median time to flare did not differ significantly between the three groups (p > 0.05). Most patients who flared regained remission rapidly after resuming YSP 50 mg QW or starting adalimumab 40 mg every other week. CONCLUSIONS: For patients with early axSpA in remission on YSP for more than 12 weeks, continuation of YSP at full dose was superior to discontinuation of YSP, but not superior to halving the dose.

18.
Exp Neurol ; 320: 112966, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31145898

RESUMO

Manipulation of developmentally regulated genes presents a promising strategy to enhance the intrinsic growth capability of adult neurons. Inhibitor of DNA binding 2 (Id2), a negative regulator of bHLH transcriptional factors, promotes axonal growth after its forced expression in post-mitotic neurons. Neurogenin2 (Ngn2) is a neural specific bHLH factor which controls neuronal fate and drives neuronal differentiation during development. In this study, we investigated the mechanism of Id2 in promoting axonal growth and revealed that Ngn2 contributed to the growth-activating role of Id2 in neurons. Ngn2 expression was upregulated with increased Id2 activity by assessing RNA and protein levels. Forced expression of Id2 or Ngn2 in cortical neurons significantly promoted axonal growth with little effect on dendrites. Furthermore, knockdown of Ngn2 impaired the axonal growth promoting effect of Id2, implying that the effect of Id2 on axonal growth depends on Ngn2. These findings suggest that elevation of neuronal Ngn2 may be a new therapeutic strategy to stimulate axonal regeneration.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Proteína 2 Inibidora de Diferenciação/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Crescimento Neuronal/fisiologia , Animais , Encéfalo/embriologia , Encéfalo/fisiologia , Camundongos , Regulação para Cima
19.
Clin Rheumatol ; 38(7): 1873-1880, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30806857

RESUMO

OBJECTIVES: To distinguish brucellosis patients fulfilling the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for spondyloarthritis (SpA) from SpA patients. METHODS: Brucellosis patients diagnosed from September 2012 to December 2017 who met the ASAS classification criteria for SpA were analyzed with clinical characteristics and laboratory and imaging examinations. Axial or peripheral SpA patients were respectively included into the comparative analysis with a 4:1 ratio. RESULTS: Twenty-two brucellosis (10 axial and 12 peripheral) patients (male, 16 cases; 72.72%; mean (S.D.) age, 40.23 (16.49) years) and 88 SpA patients were included. All brucellosis patients had been misdiagnosed or considered as SpA before admission to our center. The brucellosis patients had shorter disease duration (axial, P = 0.001; peripheral, P = 0.108). More than half (59.09%) of the patients had contact history with livestock. The low back pain (LBP) of brucellosis patients was generally less improved with exercise (axial, P = 0.001; peripheral, P = 0.008). More brucellosis patients had myalgia (axial, P < 0.001; peripheral, P = 0.071) or fever (axial, P < 0.001; peripheral, P = 0.107). None of them had positive HLA-B27. Blood culture tests were performed in all brucellosis patients and only 4 (18.18%) were positive. Twenty (90.91%) brucellosis patients were gold-immunochromatographic assay (GICA) positive. Bone marrow edema and bone erosion in sacroiliac joints were respectively detected in 100% (10/10) and 90% (9/10) axial brucellosis patients by MRI. Adjacent muscle involvement was found in 80% (8/10) of the patients. CONCLUSIONS: Indicators including disease duration, contact history of livestock, features of LBP, myalgia, fever, and HLA-B27 can help the differential diagnosis of brucellosis and SpA. GICA test and sacroiliac joints MRI can furtherly confirm the diagnosis of brucellosis.


Assuntos
Brucelose/diagnóstico , Erros de Diagnóstico/estatística & dados numéricos , Espondilartrite/classificação , Espondilartrite/diagnóstico , Adulto , Animais , Brucelose/fisiopatologia , China , Diagnóstico Diferencial , Erros de Diagnóstico/prevenção & controle , Feminino , Antígeno HLA-B27/sangue , Humanos , Dor Lombar/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sacroileíte/fisiopatologia , Sociedades Médicas , Espondilartrite/fisiopatologia , Adulto Jovem
20.
Phys Chem Chem Phys ; 20(22): 15223-15235, 2018 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-29789835

RESUMO

Combinations of nanoparticles and surfactants have been widely employed in many industrial processes, i.e., boiling and condensation in heat transfer and hydraulic fracturing in shale oil and gas production, etc. However, the underlying mechanism for various phenomena resulting from the addition of nanoparticles into the surfactant solutions is still unclear. For instance, there are contradictory conclusions from the literature regarding the variations of surface tension upon the addition of nanoparticles into surfactant solutions. In this work, the dominating factors determining if the surface activity of the surfactant solution will increase or conversely decrease when adding certain kinds of nanoparticles have been investigated. Two typical hydrophilic nanoparticles, SiO2 and TiO2 with anionic or cationic surfactants, respectively, have been considered. The surface tension has been measured in a wide range of nanoparticle and surfactant concentrations. It was found that the surface tension of the ionic surfactant solution can be further reduced only if nanoparticles of the same charge were added. For instance, a system containing 0.25 CMC SDS and 1 wt% SiO2 behaves similar to a 0.34 CMC SDS-only solution. Interestingly, the observed synergistic effect is found to be more significant if the surfactant concentration is much lower than its CMC for a given nanoparticle content. Moreover, the effect is perfectly reversible. When the nanoparticles were separated from the system, the surface tension values recovered fully to that of the pure surfactants. If nanoparticles of opposite charge were added, however, the surface tension of the surfactant solution increased. Zeta potential measurement and centrifugal treatment have been employed to reveal the interplay between nanoparticles and surfactants and the adsorption behavior of their assemblies at the liquid/air interface. Based on the experimental outcomes, a possible physical mechanism was proposed. It was concluded that the electrostatic repulsion between surfactant molecules and nanoparticles should be the dominant factor responsible for the observed reversible synergistic effect. Our study is expected to contribute to a better understanding of the interfacial phenomenon in nanoparticle-surfactant complex systems.

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