RESUMO
Follicular helper T (TFH) cells mediate germinal center reactions to generate high affinity antibodies against specific pathogens, and their excessive production is associated with the pathogenesis of systemic autoimmune diseases such as systemic lupus erythematosus (SLE). ETV5, a member of the ETS transcription factor family, promotes TFH cell differentiation in mice. In this study, we examined the role of ETV5 in the pathogenesis of lupus in mice and humans. T cell-specific deletion of Etv5 alleles ameliorated TFH cell differentiation and autoimmune phenotypes in lupus mouse models. Further, we identified SPP1 as an ETV5 target that promotes TFH cell differentiation in both mice and humans. Notably, extracellular osteopontin (OPN) encoded by SPP1 enhances TFH cell differentiation by activating the CD44-AKT signaling pathway. Furthermore, ETV5 and SPP1 levels were increased in CD4+ T cells from patients with SLE and were positively correlated with disease activity. Taken together, our findings demonstrate that ETV5 is a lupus-promoting transcription factor, and secreted OPN promotes TFH cell differentiation.
Assuntos
Diferenciação Celular , Lúpus Eritematoso Sistêmico , Osteopontina , Fatores de Transcrição , Animais , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/patologia , Osteopontina/metabolismo , Osteopontina/genética , Camundongos , Humanos , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Células T Auxiliares Foliculares/imunologia , Células T Auxiliares Foliculares/metabolismo , Feminino , Modelos Animais de Doenças , Camundongos KnockoutRESUMO
OBJECTIVE: This study determined the impact of demographic factors, clinical manifestations, disease activity, and serological tests at baseline on future SLE development in Sjögren's syndrome (SS) patients. METHODS: This retrospective study assessed 1,082 SS patients without other autoimmune diseases at baseline who visited our hospital between January 2012 and March 2021. We analyzed demographic features, extra-glandular manifestations (EGMs), clinical indices, and laboratory values at baseline between the two groups divided per future SLE development (SS/SLE group vs SS group). The probability and predictors of SLE development in SS patients were estimated using the Kaplan-Meier method and Cox proportional hazards models. RESULTS: The median follow-up duration was 1083.5 days. Forty-nine patients (4.5%) developed SLE that met the 2012 Systemic Lupus International Collaborating Clinics or 2019 EULAR/ACR classification criteria. The baseline EULAR SS disease activity index (ESSDAI) score was significantly higher in the SS/SLE group (p < .001). The SS/SLE group had more lymphadenopathy and renal involvement (p = .015 and p = .017, respectively). Shorter SS disease duration (<3 years) (hazard ratio [HR] = 2.12, p = .0328), high ESSDAI (HR = 8.24, p < .0001), leukopenia (HR = 4.17, p = .0005), thrombocytopenia (HR = 3.38, p = .0059), hypocomplementemia (HR = 29.06, p<.0001), and positive for anti-dsDNA (HR = 13.70, p < .0001), anti-ribonucleoprotein (RNP) (HR = 3.82, p = .0027), and anti-ribosomal P (HR = 6.70, p = .0002) at baseline were SLE development predictors in SS patients. CONCLUSION: Shorter disease duration and higher disease activity of SS at baseline may be risk factors for future SLE development. Serologic predictors of SLE development are hypocomplementemia, leukopenia, thrombocytopenia, and positivity for anti-dsDNA, anti-RNP, and anti-ribosomal P antibodies. If the above factors are observed, close monitoring will be necessary during the follow-up period, considering the possibility of future SLE development.
Assuntos
Leucopenia , Lúpus Eritematoso Sistêmico , Síndrome de Sjogren , Trombocitopenia , Humanos , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/epidemiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Estudos Retrospectivos , Leucopenia/epidemiologia , Leucopenia/etiologia , Anticorpos Antinucleares , Trombocitopenia/complicações , República da Coreia/epidemiologiaRESUMO
OBJECTIVES: Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease with low quality of life caused by various constitutional symptoms and glandular dysfunction. Although fatigue is one of the most frequent symptoms in pSS, its aetiology or biomarkers are poorly elucidated. We investigated potential relationship between severity of fatigue and the kynurenine pathway in pSS. METHODS: Clinical data and blood samples of 81 patients were obtained from a prospective cohort for pSS and compared with age- and sex-matched healthy controls (HC). Severity of fatigue was defined according to the fatigue domain scores in the ESSPRI. Potential biomarkers related to the kynurenine pathway were determined using ELISA. RESULTS: Of the total, 44 patients were defined as the "severe fatigue (ESSPRI fatigue ≥ 5)" group, whereas 37 as the "less fatigue (ESSPRI fatigue < 5)". Serum tryptophan levels in the severe fatigue group were significantly lower while those of kynurenine were higher. Serum interferon gamma, IDO1, and quinolinic acid levels were mostly higher in the less fatigue group. Kynurenine/tryptophan ratios were distinctly higher in the severe fatigue group than both HC and the less fatigue group (p < 0.001). This ratio showed a strong degree of positive correlation (r = 0.624, p < 0.001) with severity of fatigue in pSS while the other markers showed fair degrees of correlation. CONCLUSIONS: Serum markers related to the kynurenine pathway, especially the kynurenine/tryptophan ratio, may be associated with severity of fatigue in pSS. These results can provide guidance for further investigations on fatigue in pSS.
Assuntos
Síndrome de Sjogren , Humanos , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Cinurenina , Triptofano , Estudos Prospectivos , Qualidade de Vida , Fadiga/diagnóstico , Fadiga/etiologia , BiomarcadoresRESUMO
Zinc is a fundamental trace element essential for numerous biological processes, and zinc homeostasis is regulated by the Zrt-/Irt-like protein (ZIP) and zinc transporter (ZnT) families. ZnT7 is mainly localized in the Golgi apparatus and endoplasmic reticulum (ER) and transports zinc into these organelles. Although previous studies have reported the role of zinc in animal physiology, little is known about the importance of zinc in the Golgi apparatus and ER in animal development and neurodegenerative diseases. In this study, we demonstrated that ZnT86D, a Drosophila ortholog of ZnT7, plays a pivotal role in the neurodevelopment and pathogenesis of Alzheimer disease (AD). When ZnT86D was silenced in neurons, the embryo-to-adult survival rate, locomotor activity, and lifespan were dramatically reduced. The toxic phenotypes were accompanied by abnormal neurogenesis and neuronal cell death. Furthermore, knockdown of ZnT86D in the neurons of a Drosophila AD model increased apoptosis and exacerbated neurodegeneration without significant changes in the deposition of amyloid beta plaques and susceptibility to oxidative stress. Taken together, our results suggest that an appropriate distribution of zinc in the Golgi apparatus and ER is important for neuronal development and neuroprotection and that ZnT7 is a potential protective factor against AD.
Assuntos
Doença de Alzheimer , Proteínas de Transporte de Cátions , Oligoelementos , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Oligoelementos/metabolismo , Zinco/metabolismoRESUMO
OBJECTIVES: To investigate whether temporal changes in immunoglobulin (Ig) levels and persistent hypergammaglobulinaemia cause glandular and extra-glandular damage in patients with primary Sjögren's syndrome (pSS). METHODS: Cumulative demographics and clinical and serological data from pSS patients in the Korean Initiative pSS cohort were evaluated. Persistent hypergammaglobulinaemia was defined as mean IgG levels of ≥1600 mg/dL over 3 years. Salivary gland damage was assessed by measuring salivary flow impairment, and lacrimal gland damage was assessed by examining ocular structural abnormalities. Solid organ damage included neurological and pleuropulmonary damage, renal impairment and lymphoproliferative disease. Independent predictors of glandular and extra-glandular damage in the third year were identified by logistic regression. RESULTS: Of 256 patients with pSS (median age, 55 years; 98% female), 47% had hypergammaglobulinaemia at baseline. IgG levels fell during the first 2 years in patients with hypergammaglobulinaemia at baseline, but not in those with normal IgG levels. Changes in IgG levels were associated with hydroxychloroquine and glucocorticoids. In the third year of follow-up, salivary flow impairment and solid organ damage were present in 71% and 9% of patients, respectively. After adjusting for age and medication use, persistent hypergammaglobulinaemia was associated with salivary flow impairment and solid organ damage in the third year. Patients in whom IgG fell by more than 80 mg/dL from baseline over 2 years showed less solid organ damage. CONCLUSIONS: Persistent hypergammaglobulinaemia was associated with salivary gland and solid organ damage. Decreased IgG may attenuate progression to solid organ dysfunction.
Assuntos
Aparelho Lacrimal , Síndrome de Sjogren , Estudos de Coortes , Feminino , Humanos , Hipergamaglobulinemia , Masculino , Pessoa de Meia-Idade , Glândulas Salivares , Síndrome de Sjogren/diagnósticoRESUMO
Neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), are disorders characterized by progressive degeneration of the nervous system. Currently, there is no disease-modifying treatments for most NDs. Meanwhile, numerous studies conducted on human and animal models over the past decades have showed that exercises had beneficial effects on NDs. Inter-tissue communication by myokine, a peptide produced and secreted by skeletal muscles during exercise, is thought to be an important underlying mechanism for the advantages. Here, we reviewed studies about the effects of myokines regulated by exercise on NDs and their mechanisms. Myokines could exert beneficial effects on NDs through a variety of regulatory mechanisms, including cell survival, neurogenesis, neuroinflammation, proteostasis, oxidative stress, and protein modification. Studies on exercise-induced myokines are expected to provide a novel strategy for treating NDs, for which there are no adequate treatments nowadays. To date, only a few myokines have been investigated for their effects on NDs and studies on mechanisms involved in them are in their infancy. Therefore, future studies are needed to discover more myokines and test their effects on NDs.
Assuntos
Citocinas/metabolismo , Exercício Físico/fisiologia , Músculo Esquelético/metabolismo , Doenças Neurodegenerativas/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/fisiopatologia , Animais , Humanos , Doença de Huntington/metabolismo , Doença de Huntington/fisiopatologia , Doenças Neurodegenerativas/fisiopatologia , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologiaRESUMO
OBJECTIVES: The presence and severity of focal lymphocytic sialadenitis in minor salivary glands is a pathognomonic feature in primary Sjögren's syndrome (pSS). However, it has not been determined whether performing minor salivary gland biopsy (MSGB) in a setting of serologically and clinically established pSS provides additional clinical value. Therefore, we aimed to investigate the necessity of MSGB in established pSS patients with anti-Ro/SSA antibodies. METHODS: We extracted 185 patients with anti-Ro/SSA antibody-positive pSS from the Korean Initiative of pSS study, a prospective cohort study. We assigned them into two groups, 161 patients with focus scores ≥1 and another 24 with focus scores <1. The two groups were compared in various clinical aspects, including the severity of glandular dysfunction, systemic disease activity, extra- glandular manifestations, and other clinical indices and laboratory values. We also evaluated the relationship between focus scores and clinically important variables in pSS. RESULTS: Between the two groups, there were no significant differences in the severity of secretory dysfunction, the frequency of extra-glandular manifestations, systemic disease activity represented by various clinical indices, and laboratory findings possibly predicting the risk for lymphoma. Rather, theSjögren's syndrome disease damage index was higher in the group with focusscores <1. Among all variables, only serum immunoglobulin G levels were correlated with focus scores. CONCLUSIONS: Given the little influence on clinical phenotypes, routine MSGB could be omitted for serologically and clinically established pSS patients, especially in low-risk areas for lymphoproliferative diseases.
Assuntos
Síndrome de Sjogren , Humanos , Estudos Prospectivos , República da Coreia/epidemiologia , Glândulas Salivares , Glândulas Salivares Menores , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/epidemiologiaRESUMO
OBJECTIVES: To investigate clinical characteristics of patients with primary Sjögren's syndrome (SS) who were negative for anti-Ro/SSA antibody but positive for minor salivary gland biopsy (MSGB) compared to patients who presented positivity for anti-Ro/SSA antibody. METHODS: The data of 355 patients from the Korean Initiative of primary Sjögren's Syndrome (KISS), a nationwide prospective cohort for primary SS in Korea, were analysed. All patients fulfilled the 2016 American College of Rheumatology/European League Against Rheumatism (EULAR) classification criteria. Of these patients, 326 were positive for anti-Ro/SSA antibody and 29 were antibody-negative, although they had positive findings in MSGB. Various clinical features including all kinds of tests for evaluating secretory function, disease-related clinical indices and serological values available in the cohort were compared between the two groups. RESULTS: The anti-Ro/SSA-negative group showed less rheumatoid factor positivity (p<0.001), leucopenia (p=0.003), hyper-gammaglobulinaemia (p<0.001), lower serum ß2-microglobulin level (p=0.034), more anti-centromere antibody positivity (p<0.001), higher score in dryness domain of EULAR SS patient-reported index (p=0.048) and more positivity for peripheral nervous system domain in EULAR SS disease activity index and loss of teeth in SS disease damage index (p=0.021 and 0.041, respectively) than patients who were positive for anti-Ro/ SSA antibody. CONCLUSIONS: Primary SS patients who are negative for anti-Ro/SSA antibody have different clinical characteristics compared to patients who are positive for such antibody in Korea. Therefore, clinicians should consider MSGB in patients with suspicious symptoms who are anti-Ro/SSA-negative.
Assuntos
Anticorpos Antinucleares/imunologia , Glândulas Salivares Menores/imunologia , Síndrome de Sjogren , Humanos , Estudos Prospectivos , República da Coreia , Fator Reumatoide , Glândulas Salivares Menores/patologia , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/patologiaRESUMO
OBJECTIVE: The purpose of this study was to examine whether enterotypes in the gut microbiome could be determined by clustering validity indexes and whether these enterotypes were associated with individual differences in temperament traits. METHODS: Sixty healthy Korean participants (21 men; 27.5 [8.1] years, 39 women; 34.5 [14.3] years) were asked to answer 60 temperament questions (novelty seeking, harm avoidance, reward dependence, and persistence) from the Korean version of the Temperament and Character Inventory-125. The participants' stool samples were submitted, and relative operational taxonomic units were calculated using 16S rRNA gene-based microarrays. Differences between sexes and age-related effects on the temperament and operational taxonomic unit abundances were determined, and optimal clustering numbers related to enterotypes were examined using connectivity and silhouette width (SW) indexes. Finally, the differences in temperament between enterotypes were examined. RESULTS: There was no significant effect of sex or age on gut microbiota and temperament scores. The hierarchical dendrogram, connectivity, and SW analysis indicated bimodal enterotypes. Bacteroidaceae were more abundant in enterotype 1 (46.24%, N = 45), whereas Prevotellaceae were more abundant in enterotype 2 (43.83%, n = 15). Among the four temperament dimensions, novelty seeking and reward dependence scores were higher in enterotype 1 (10.82 [2.99] and 8.07 [2.51] points) than in enterotype 2 (8.87 [2.42] and 5.73 [1.03] points). CONCLUSIONS: The results suggest an association between temperament and enterotypes in healthy Korean adults. It is conceivable that this association may develop early in life as a result of biological processes catalyzed by the gut microbiota during infancy.
Assuntos
Fezes/microbiologia , Microbioma Gastrointestinal/fisiologia , RNA Ribossômico 16S/classificação , Temperamento/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , República da Coreia , Temperamento/classificação , Adulto JovemRESUMO
BACKGROUND: Acupuncture treatments that regulate the heart are used to treat various clinical disorders and conditions. Although many studies have been conducted to measure quantitatively the effects of acupuncture, thus far, models that describe these effects have not been established. The purpose of this study was to derive a transfer function model of acupuncture stimulation within the electrocardiograms based on the periods before, during, and after acupuncture. METHODS: Fourteen healthy subjects were included in this clinical trial. Five-minute electrocardiograms were captured before, during, and after acupuncture at HT7. For each period, signal-averaged electrocardiograms were created from all of the subjects' 5-min electrocardiograms for that period. Individual transfer functions, which has the highest average goodness of fit, were derived for each period pair. By averaging individual transfer functions, generalized transfer functions were derived. RESULTS: The transfer function with the highest average goodness of fit was a fraction with 4th order numerator and 5th order denominator. Fourteen individual transfer functions were derived separately for each pair of periods: before and during acupuncture, during and after acupuncture, and before and after acupuncture. Three generalized transfer functions were derived by averaging individual transfer functions for each period pair. CONCLUSION: The three generalized transfer functions that were derived may reflect the electrocardiogram changes caused by acupuncture. However, this clinical trial included only 14 subjects. Further studies with control groups and more subjects are needed. This clinical trial has been registered on the Clinical Research Information Service, Republic of Korea (No. KCT0001944). The first enrolment of subject started at 2 June 2015 and this trial was retrospectively registered at 14 June 2016.
Assuntos
Terapia por Acupuntura , Eletrocardiografia , Medicina Tradicional Coreana , Adulto , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Adulto JovemRESUMO
OBJECTIVE: To examine whether color parameters of tongue inspection (TI) using a digital camera was reliable and valid, and to examine which color parameters serve as predictors of symptom patterns in terms of East Asian medicine (EAM). METHODS: Two hundred female subjects' tongue substances were photographed by a mega-pixel digital camera. Together with the photographs, the subjects were asked to complete Yin deficiency, Phlegm pattern, and Cold-Heat pattern questionnaires. Using three sets of digital imaging software, each digital image was exposure- and white balance-corrected, and finally L* (luminance), a* (red-green balance), and b* (yellow-blue balance) values of the tongues were calculated. To examine intra- and inter-rater reliabilities and criterion validity of the color analysis method, three raters were asked to calculate color parameters for 20 digital image samples. Finally, four hierarchical regression models were formed. RESULTS: Color parameters showed good or excellent reliability (0.627-0.887 for intra-class correlation coefficients) and significant criterion validity (0.523-0.718 for Spearman's correlation). In the hierarchical regression models, age was a significant predictor of Yin deficiency (ß = 0.192), and b* value of the tip of the tongue was a determinant predictor of Yin deficiency, Phlegm, and Heat patterns (ß = - 0.212, - 0.172, and - 0.163). Luminance (L*) was predictive of Yin deficiency (ß = -0.172) and Cold (ß = 0.173) pattern. CONCLUSION: Our results suggest that color analysis of the tongue using the L*a*b* system is reliable and valid, and that color parameters partially serve as symptom pattern predictors in EAM practice.
Assuntos
Diagnóstico Diferencial , Medicina Tradicional do Leste Asiático/métodos , Língua/química , Deficiência da Energia Yin/diagnóstico , Adolescente , Adulto , Idoso , Cor , Feminino , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto JovemRESUMO
INTRODUCTION: Coupling motions (CMs) are the motions occurring in different directions around the primary motion. As low back pain (LBP) is known to be associated with lumbar CMs, some studies measured lumbar CMs using the microelectromechanical system inertial measurement unit (MEMS-IMU) because of its low cost and small size. This study aimed to examine the reliability of lumbar CM measurements using the MEMS-IMU and to classify the individual characteristics of lumbar CMs. METHODS: MEMS-IMUs were attached to the two lumbar points (L1, L5) of 19 male volunteers (age, 24.3 ± 1.2 years). Following an instructional video and audio recording, they conducted the six lumbar movements three times: flexion and extension, left and right lateral bending, and left and right rotation. The six lumbar movements were repeated after 1 h. Raw data were transformed into angle data using MATLAB. Intraclass correlation coefficients (ICCs) were calculated to evaluate intratest repeatability and test-retest reliability. Finally, angle data were analyzed to examine whether individual characteristics of lumbar CMs could be identified. RESULTS: Lumbar CM measurements showed fair to good or excellent intratest repeatability and test-retest reliability, ranging from 0.669 to 0.997 of the ICCs. All lumbar CMs could be categorized into six types, and flexion and extension CMs were more prominent than other CMs. CONCLUSIONS: Lumbar CM measurements obtained using the MEMS-IMU are reliable, and identifying the individual variations of lumbar CMs may be helpful for alleviating chronic or recurrent LBP.
Assuntos
Dor Lombar/fisiopatologia , Vértebras Lombares/fisiologia , Amplitude de Movimento Articular , Adulto , Artrometria Articular/métodos , Humanos , Masculino , Movimento/fisiologia , Reprodutibilidade dos Testes , Rotação , Adulto JovemRESUMO
This study aimed to investigate the effect of bortezomib in the desensitization and treatment of acute antibody mediated rejection (AAMR) in kidney transplantation. Nine patients who received bortezomib therapy for desensitization (DSZ group, n = 3) or treatment of AAMR (AAMR group, n = 6) were included in this study. In the DSZ group, 2 patients required DSZ owing to positive cross match and 1 owing to ABO mismatch with high baseline anti-ABO antibody titer (1:1,024). Bortezomib was used at 1, 3, 8, and 11 days from the start of the treatment. In the AAMR group, 3 patients showed full recovery of allograft function after bortezomib use and decrease in donor specific anti-HLA antibody (HLA-DSA). However, 3 patients did not respond to bortezomib and experienced allograft failure. In the DSZ group, negative conversion of T-CDC (complement-dependent cytotoxicity) was achieved, and HLA-DSA was decreased to lower than a weak level (median fluorescence intensity [MFI] < 5,000) in 2 patients. In the case of ABO mismatch kidney transplantation, the anti-A/B antibody titer decreased to below the target (≤ 1:16) after bortezomib therapy. Therefore, bortezomib could be an alternative therapeutic option for desensitization and treatment of AAMR that is unresponsive to conventional therapies.
Assuntos
Ácidos Borônicos/uso terapêutico , Dessensibilização Imunológica/métodos , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/prevenção & controle , Transplante de Rim/métodos , Pirazinas/uso terapêutico , Adulto , Bortezomib , Feminino , Antígenos HLA/imunologia , Humanos , Rim/cirurgia , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Background: Yin deficiency (YD) is a pathological condition characterized by emaciation, afternoon fever, dry mouth, and night sweats. The incidence of YD is 23.3%. A 27-item Yin Deficiency Scale (YDS) was developed to estimate the clinical severity of YD. This study aimed to develop three short-form YDS versions to reduce the burden of response time, using three item-reduction approaches: Rasch, equidiscriminatory item-total correlation (EITC), and factor-based analyses. Methods: Two datasets were analyzed from previous studies (169 outpatients from May to June 2009 and 237 healthy college students from January to April 2016). The optimal response category was examined using Rasch analysis. Items with higher item-total correlations were determined using the EITC. Using a factor-based approach, the items were reduced, while maintaining the original YDS construct. Reliability was estimated using the person separation index (PSI) and Cronbach's α values. The predictive accuracy was examined using the area under the curve (AUC). Finally, the relationship between YD and dysfunctional breathing (DB) was examined using factor scores from the YDS and the Korean version of the Nijmegen Questionnaire (KNQ). Results: We developed two 14-item YDS versions using the Rasch and EITC approaches, and a 16-item YDS version using a factor-based approach. Rasch analysis suggested an optimal response category of five points. The PSI of Rasch and Cronbach's α of the EITC and factor-based versions were 2.19, 0.855, and 0.827. The AUCs of the three short-form YDS were 0.812, 0.811, and 0.818. The sensitivity of the EITC-YDS was 0.632, which was lower than its specificity of 0.875. The fatigue-related scores of the factor-based YDS were fairly correlated with the factor scores of the KNQ estimating the DB (r = 0.349-0.499). Conclusion: The 14-item Rasch- and 16-item factor-based YDS may replace the original YDS during YD's primary screening, epidemiological surveys, and health checkups.
RESUMO
Urban safety plays an essential role in the quality of citizens' lives and in the sustainable development of cities. In recent years, researchers have attempted to apply machine learning techniques to identify the role of location-specific attributes in the development of urban safety. However, existing studies have mainly relied on limited images (e.g., map images, single- or four-directional images) of areas based on a relatively large geographical unit and have narrowly focused on severe crime rates, which limits their predictive performance and implications for urban safety. In this work, we propose a novel method that predicts "deviance," which includes formal deviant crimes (e.g., murders) and informal deviant behaviors (e.g., loud parties at night). To do this, we first collect a large-scale geo-tagged dataset consisting of incident report data for seven metropolitan cities, along with corresponding sequential images around incident sites obtained from Google Street View. We then design a convolutional neural network that learns spatio-temporal visual attributes of deviant streets. Experimental results show that our framework is able to reliably recognize real-world deviance in various cities. Furthermore, we analyze which visual attribute is important for deviance identification and severity estimation with respect to social science as well as activated feature maps in the neural network. We have released our dataset and source codes on https://github.com/JinhwiPark/DevianceNet/.
RESUMO
Nuclear factor of activated T-cells 5 (NFAT5), an osmo-sensitive transcription factor, can be activated by isotonic stimuli, such as infection. It remains unclear, however, whether NFAT5 is required for damage-associated molecular pattern-triggered (DAMP-triggered) inflammation and immunity. Here, we found that several DAMPs increased NFAT5 expression in macrophages. In particular, serum amyloid A (SAA), primarily generated by the liver, substantially upregulated NFAT5 expression and activity through TLR2/4-JNK signalling pathway. Moreover, the SAA-TLR2/4-NFAT5 axis promoted migration and chemotaxis of macrophages in an IL-6- and chemokine ligand 2-dependent (CCL2-dependent) manner in vitro. Intraarticular injection of SAA markedly accelerated macrophage infiltration and arthritis progression in mice. By contrast, genetic ablation of NFAT5 or TLR2/4 rescued the pathology induced by SAA, confirming the SAA-TLR2/4-NFAT5 axis in vivo. Myeloid-specific depletion of NFAT5 also attenuated SAA-accelerated arthritis. Of note, inflammatory arthritis in mice strikingly induced SAA overexpression in the liver. Conversely, forced overexpression of the SAA gene in the liver accelerated joint damage, indicating that the liver contributes to bolstering chronic inflammation at remote sites by secreting SAA. Collectively, this study underscores the importance of the SAA-TLR2/4-NFAT5 axis in innate immunity, suggesting that acute phase reactant SAA mediates mutual interactions between liver and joints and ultimately aggravates chronic arthritis by enhancing macrophage activation.
Assuntos
Artrite , Proteína Amiloide A Sérica , Animais , Camundongos , Artrite/metabolismo , Inflamação/patologia , Fígado/metabolismo , Ativação de Macrófagos , Proteína Amiloide A Sérica/genética , Proteína Amiloide A Sérica/metabolismo , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Objective: This study aimed to compare the association between fasting plasma glucose (FPG) and glycosylated hemoglobin A1c (HbA1c) levels using the second derivative of photoplethysmogram (SDPTG) index and the cardio-ankle vascular index (CAVI). Methods: Electronic medical records of 276 participants (160 men, 116 women) who visited the health promotion center of a university hospital were examined. Age, sex, body mass index (BMI), blood pressure, and lipid profile were considered as risk factors for arterial stiffness, together with the FPG, HbA1c, CAVI, and SDPTG indices. Hierarchical regression models were constructed, and all participants were divided into low-normal, high-normal, prediabetic, and diabetic groups to examine the group-based differences in CAVI and SDPTG indices. Results: FPG and HbA1c were independently predictive of increased CAVI, and their predictive powers for CAVI were equivalent (ß = 0.214 and 0.200, respectively). Risk factors, including age, BMI, and male sex, were also predictive of CAVI (ß= 0.593-0.630, -0.256 - -0.280, and 0.142-0.178, respectively). None of the FPG and HbA1c values were predictive of the SDPTG indices. The CAVI was higher in the diabetes group than in the other three groups according to HbA1c level, while the d/a index of the SDPTG decreased in the prediabetes group and increased in the diabetes group. Conclusions: CAVI may not be substituted for SDPTG indices when evaluating arterial stiffness based on the glucose level. Moreover, the progression rate of arterial stiffness may differ between the diabetic and nondiabetic stages.
Assuntos
Diabetes Mellitus , Estado Pré-Diabético , Rigidez Vascular , Humanos , Masculino , Feminino , Glicemia , Hemoglobinas Glicadas , Rigidez Vascular/fisiologia , Tornozelo/irrigação sanguínea , Fotopletismografia , Estado Pré-Diabético/diagnósticoRESUMO
This study aimed to examine whether the 3 harmonic components (HCs) of photoplethysmography (PTG) - total harmonic distortion (THD), harmonic power (HP), and normalized harmonic amplitude (HA) - have aging effects and may serve as an arterial stiffness marker and examine the relationship between HCs and clinical severity of pathological patterns. This study had a retrospective chart review design, and electronic medical records of 173 female patients (age: 38.57 ± 11.64 years) were reviewed. Patients were asked to complete the phlegm, blood stasis (BS), and food retention (FR) pattern questionnaires and underwent PTG and the second derivative of PTG measurements. THD, HP, and HA data were extracted till the 12th HCs from the raw PTG data. THD and HA had an aging effect (ß: -0.179 to -0.278) and were related to b/a (r: -02.76 to -0.455) and d/a (r: 0.265-0.360) of the second derivative of PTG. In the younger group (≤33 years), HP and HA were positively correlated with phlegm, BS, and FR patterns (r: 0.257-0.370), while HP was positively correlated with the FR pattern (r: 0.278-0.315) in the middle age group (34-45 years). In the older group (≥46 years), HP and HA were positively or negatively correlated with the phlegm pattern (r: ±0.263 to ±0.440). HCs may serve as an arterial stiffness marker, and may be partially related to phlegm, BS, and FR patterns. Aging effect needs to be considered when utilizing HCs as an indicator of phlegm, BS, and FR patterns.
Assuntos
Muco , Fotopletismografia , Pessoa de Meia-Idade , Humanos , Feminino , Adulto , Estudos Transversais , Estudos Retrospectivos , EnvelhecimentoRESUMO
Aggression in horses may cause serious accidents during riding and non-riding activities. Hence, predicting the temperament of horses is essential for selecting suitable horses and ensuring safety during the activity. In certain animals, such as hamsters, plasma melatonin concentrations have been correlated with aggressive behavior. However, whether this relationship applies to horses remains unclear. To address this research gap, this study aimed to evaluate differences in the plasma melatonin concentrations among horses of different breeds, ages, and sexes and examine the correlation between plasma melatonin concentrations and the temperament of the horses, including docility, affinity, dominance, and trainability. Blood samples from 32 horses were collected from the Horse Industry Complex Center of Jeonju Kijeon College. The docility, affinity, dominance, and trainability of the horses were assessed by three professional trainers who were well-acquainted with the horses. Plasma melatonin concentrations were measured using an enzyme-linked immunosorbent assay. The consequent values were compared between the horses of different breeds, ages, and sexes using a three-way analysis of variance and least significant difference post hoc test. Linear regression analysis was employed to identify the relationship between plasma melatonin concentrations and docility, affinity, dominance, and trainability. The results showed that the plasma melatonin concentrations significantly differed with breeds in Thoroughbred and cold-blooded horses. However, there were no differences in the plasma melatonin concentrations between the horse ages and sexes. Furthermore, plasma melatonin concentrations did not exhibit a significant correlation with the ranking of docility, affinity, dominance, and trainability.