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Ontology is essential for achieving health information and information technology application interoperability in the biomedical fields and beyond. Traditionally, ontology construction is carried out manually by human domain experts (HDE). Here, we explore an active learning approach to automatically identify candidate terms from publications, with manual verification later as a part of a deep learning model training and learning process. We introduce the overall architecture of the active learning pipeline and present some preliminary results. This work is a critical and complementary component in addition to manually building the ontology, especially during the long-term maintenance stage.
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Ontologias Biológicas , Humanos , Terminologia como Assunto , Aprendizagem Baseada em Problemas , Aprendizado de Máquina Supervisionado , Vocabulário ControladoRESUMO
Mucoepidermoid carcinoma (MEC) is a common malignancy arising in the parotid gland. The diagnosis of MEC is typically based on its morphological features alone, characteristically containing mucocytes, intermediate cells and epidermoid cells. However, when cystic degeneration is diffuse, it is challenging to distinguish MEC from other benign cystic tumors. This is a case report of a 58-year-old Caucasian man who presented with a parotid mass. H&E sections of the mass reveal multiloculated cysts lined by bland-looking epithelium with only rare papillary architectures. The papillary proliferation contains mucocytes, and epidermoid cells highlighted by the p63 immunohistochemistry study. The diagnosis was confirmed by FISH result of positive MAML2 (11q21) rearrangement. Patient underwent parotidectomy and is disease-free 6 months post-surgery. MEC with cystic degeneration is a common diagnostic pitfall which can mimic many benign lesions in the salivary gland. We present a rare case with MEC with extensive cystic change, its molecular and pathologic findings and review the diagnostic features of MEC, its benign mimickers and useful tools for distinguishing these entities.
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The purpose of the present study was to determine the effects of obesity and biological sex on myostatin expression in humans and to examine the direct effects of myostatin, SMAD2, and SMAD3 on insulin signaling in primary human skeletal muscle cells (HSkMCs). For cohort 1, 15 lean [body mass index (BMI): 22.1 ± 0.5 kg/m2; n = 8 males; n = 7 females] and 14 obese (BMI: 40.6 ± 1.4 kg/m2; n = 7 males; n = 7 females) individuals underwent skeletal muscle biopsies and an oral glucose tolerance test. For cohort 2, 14 young lean (BMI: 22.4 ± 1.9 kg/m2; n = 6 males; n = 8 females) and 14 obese (BMI: 39.3 ± 7.9 kg/m2; n = 6 males; n = 8 females) individuals underwent muscle biopsies for primary HSkMC experiments. Plasma mature myostatin (P = 0.041), skeletal muscle precursor myostatin (P = 0.048), and skeletal muscle SMAD3 (P = 0.029) were elevated in obese females compared to lean females, and plasma mature myostatin (r = 0.58, P = 0.029) and skeletal muscle SMAD3 (r = 0.56, P = 0.037) were associated with insulin resistance in females but not males. Twenty-four hours of myostatin treatment impaired insulin signaling in primary HSkMCs derived from females (P < 0.024) but not males. Overexpression of SMAD3, but not SMAD2, impaired insulin-stimulated AS160 phosphorylation in HSkMCs derived from lean females (-27%, P = 0.040), whereas silencing SMAD3 improved insulin-stimulated AS160 phosphorylation and insulin-stimulated glucose uptake (25%, P < 0.014) in HSkMCs derived from obese females. These results suggest for the first time that myostatin-induced impairments in skeletal muscle insulin signaling are sex specific and that increased body fat in females is associated with detrimental elevations in myostatin and SMAD3, which contribute to obesity-related insulin resistance.NEW & NOTEWORTHY Obesity is considered a main risk factor for the development of insulin resistance and type 2 diabetes. The present study utilizes in vivo and in vitro experiments in human skeletal muscle to demonstrate for the first time that females are inherently more susceptible to myostatin-induced insulin resistance, which is further enhanced with obesity due to increased myostatin and SMAD3 expression.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Feminino , Humanos , Masculino , Insulina/farmacologia , Fibras Musculares Esqueléticas , Músculo Esquelético , Miostatina , Obesidade , Proteína Smad3RESUMO
Currently, there is a paucity of highly specific and sensitive markers to identify breast carcinoma in male patients. Immunohistochemical stains commonly used for unmasking primary breast carcinomas include estrogen receptor (ER) and GATA3. However, these markers are commonly expressed in carcinomas originating from other organ systems and can be reduced in breast carcinomas with higher histologic grades. Androgen receptor (AR) may be used to highlight primary male breast cancer, but this marker can also be expressed in other carcinomas. We evaluated TRPS1, a highly sensitive and specific marker for female breast carcinoma, in cases of male breast carcinoma. Through an institutional database search, we identified 72 cases of primary invasive breast carcinoma in male patients. Among ER/progesterone receptor (PR)-positive cancers, 97% showed intermediate or high positivity for both TRPS1 and GATA3. Among HER2-positive cancers, 100% showed intermediate or high positivity for TRPS1 and GATA3. One case of triple-negative breast cancer was collected, showing high positivity for TRPS1 and negativity for GATA3. AR staining was non-specific and heterogeneous: 76% showed high positivity, but the remaining 24% showed low or intermediate positivity. Additionally, among 29 cases of metastatic carcinoma to male breast tissue, 93% were negative for TRPS1, and the remaining 2 cases (7%), which were carcinomas from salivary gland primary tumors, were intermediate positive. TRPS1 is a sensitive and specific marker in the unmasking of male primary invasive breast carcinoma across different subtypes. Additionally, TRPS1 is not expressed in metastatic carcinomas of multiple primaries, with the exception of salivary gland primaries.
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Neoplasias da Mama Masculina , Neoplasias da Mama , Feminino , Humanos , Masculino , Biomarcadores Tumorais , Neoplasias da Mama Masculina/genética , Fator de Transcrição GATA3 , Doenças do Cabelo , Síndrome de Langer-Giedion , Receptores de Estrogênio , Proteínas Repressoras , Neoplasias de Mama Triplo NegativasRESUMO
Interoperable clinical decision support system (CDSS) rules provide a pathway to interoperability, a well-recognized challenge in health information technology. Building an ontology facilitates creating interoperable CDSS rules, which can be achieved by identifying the keyphrases (KP) from the existing literature. However, KP identification for data labeling requires human expertise, consensus, and contextual understanding. This paper aims to present a semi-supervised KP identification framework using minimal labeled data based on hierarchical attention over the documents and domain adaptation. Our method outperforms the prior neural architectures by learning through synthetic labels for initial training, document-level contextual learning, language modeling, and fine-tuning with limited gold standard label data. To the best of our knowledge, this is the first functional framework for the CDSS sub-domain to identify KPs, which is trained on limited labeled data. It contributes to the general natural language processing (NLP) architectures in areas such as clinical NLP, where manual data labeling is challenging, and light-weighted deep learning models play a role in real-time KP identification as a complementary approach to human experts' effort.
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BACKGROUND: Clinical decision support systems (CDSSs) are important for the quality and safety of health care delivery. Although CDSS rules guide CDSS behavior, they are not routinely shared and reused. OBJECTIVE: Ontologies have the potential to promote the reuse of CDSS rules. Therefore, we systematically screened the literature to elaborate on the current status of ontologies applied in CDSS rules, such as rule management, which uses captured CDSS rule usage data and user feedback data to tailor CDSS services to be more accurate, and maintenance, which updates CDSS rules. Through this systematic literature review, we aim to identify the frontiers of ontologies used in CDSS rules. METHODS: The literature search was focused on the intersection of ontologies; clinical decision support; and rules in PubMed, the Association for Computing Machinery (ACM) Digital Library, and the Nursing & Allied Health Database. Grounded theory and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines were followed. One author initiated the screening and literature review, while 2 authors validated the processes and results independently. The inclusion and exclusion criteria were developed and refined iteratively. RESULTS: CDSSs were primarily used to manage chronic conditions, alerts for medication prescriptions, reminders for immunizations and preventive services, diagnoses, and treatment recommendations among 81 included publications. The CDSS rules were presented in Semantic Web Rule Language, Jess, or Jena formats. Despite the fact that ontologies have been used to provide medical knowledge, CDSS rules, and terminologies, they have not been used in CDSS rule management or to facilitate the reuse of CDSS rules. CONCLUSIONS: Ontologies have been used to organize and represent medical knowledge, controlled vocabularies, and the content of CDSS rules. So far, there has been little reuse of CDSS rules. More work is needed to improve the reusability and interoperability of CDSS rules. This review identified and described the ontologies that, despite their limitations, enable Semantic Web technologies and their applications in CDSS rules.
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Elevated circulating lactate has been associated with obesity and insulin resistance. The aim of the current study was to determine if lactate-induced lysine lactylation (kla), a post-translational modification, was present in human skeletal muscle and related to insulin resistance. Fifteen lean (Body Mass Index: 22.1 ± 0.5 kg/m2) and fourteen obese (40.6 ± 1.4 kg/m2) adults underwent a muscle biopsy and 2-h oral glucose tolerance test. Skeletal muscle lactylation was increased in obese compared to lean females (19%, p < 0.05) and associated with insulin resistance (r = 0.37, p < 0.05) in the whole group. Skeletal muscle lactylation levels were significantly associated with markers of anaerobic metabolism (plasma lactate and skeletal muscle lactate dehydrogenase [LDH], p < 0.05) and negatively associated with markers of oxidative metabolism (skeletal muscle cytochrome c oxidase subunit 4 and Complex I [pyruvate] OXPHOS capacity, p < 0.05). Treatment of primary human skeletal muscle cells (HSkMC) with sodium lactate for 24 h increased protein lactylation and IRS-1 serine 636 phosphorylation in a similar dose-dependent manner (p < 0.05). Inhibition of glycolysis (with 2-deoxy-d-glucose) or LDH-A (with sodium oxamate or LDH-A siRNA) for 24 h reduced HSkMC lactylation which paralleled reductions in culture media lactate accumulation. This study identified the existence of a lactate-derived post-translational modification in human skeletal muscle and suggests skeletal muscle lactylation could provide additional insight into the regulation of skeletal muscle metabolism, including insulin resistance.
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BACKGROUND: Disease status (eg, cancer stage) has been used in routine clinical practice to determine more accurate treatment plans. Health-related indicators, such as mortality, morbidity, and population group life expectancy, have also been used. However, few studies have specifically focused on the comprehensive and objective measures of individual health status. OBJECTIVE: The aim of this study was to analyze the perspectives of the public toward 29 health indicators obtained from a literature review to provide evidence for further prioritization of the indicators. The difference between health status and disease status should be considered. METHODS: This study used a cross-sectional design. Online surveys were administered through Ohio University, ResearchMatch, and Clemson University, resulting in three samples. Participants aged 18 years or older rated the importance of the 29 health indicators. The rating results were aggregated and analyzed as follows (in each case, the dependent variables were the individual survey responses): (1) to determine the agreement among the three samples regarding the importance of each indicator, where the independent variables (IVs) were the three samples; (2) to examine the mean differences between the retained indicators with agreement across the three samples, where the IVs were the identified indicators; and (3) to rank the groups of indicators into various levels after grouping the indicators with no mean differences, where the IVs were the groups of indicators. RESULTS: In total, 1153 valid responses were analyzed. Descriptive statistics revealed that the top five-rated indicators were drug or substance abuse, smoking or tobacco use, alcohol abuse, major depression, and diet and nutrition. Among the 29 health indicators, the three samples agreed upon the importance of 13 indicators. Inferential statistical analysis indicated that some of the 13 indicators held equal importance. Therefore, the 13 indicators were categorized by rank into seven levels: level 1 included blood sugar level and immunization and vaccination; level 2 included LDL cholesterol; level 3 included HDL cholesterol, blood triglycerides, cancer screening detection, and total cholesterol; level 4 included health literacy rate; level 5 included personal care needs and air quality index greater than 100; level 6 included self-rated health status and HIV testing; and level 7 included the supply of dentists. Levels 1 to 3 were rated significantly higher than levels 4 to 7. CONCLUSIONS: This study provides a baseline for prioritizing 29 health indicators, which can be used by electronic health record or personal health record system designers or developers to determine what can be included in the systems to capture an individual's health status. Currently, self-rated health status is the predominantly used health indicator. Additionally, this study provides a foundation for tracking and measuring preventive health care services more accurately and for developing an individual health status index.
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Indicadores Básicos de Saúde , Nível de Saúde , Estudos Transversais , Humanos , Planejamento de Assistência ao Paciente , Inquéritos e QuestionáriosRESUMO
BACKGROUND: MetaMap is a valuable tool for processing biomedical texts to identify concepts. Although MetaMap is highly configurative, configuration decisions are not straightforward. OBJECTIVE: To develop a systematic, data-driven methodology for configuring MetaMap for optimal performance. METHODS: MetaMap, the word2vec model, and the phrase model were used to build a pipeline. For unsupervised training, the phrase and word2vec models used abstracts related to clinical decision support as input. During testing, MetaMap was configured with the default option, one behavior option, and two behavior options. For each configuration, cosine and soft cosine similarity scores between identified entities and gold-standard terms were computed for 40 annotated abstracts (422 sentences). The similarity scores were used to calculate and compare the overall percentages of exact matches, similar matches, and missing gold-standard terms among the abstracts for each configuration. The results were manually spot-checked. The precision, recall, and F-measure (ß =1) were calculated. RESULTS: The percentages of exact matches and missing gold-standard terms were 0.6-0.79 and 0.09-0.3 for one behavior option, and 0.56-0.8 and 0.09-0.3 for two behavior options, respectively. The percentages of exact matches and missing terms for soft cosine similarity scores exceeded those for cosine similarity scores. The average precision, recall, and F-measure were 0.59, 0.82, and 0.68 for exact matches, and 1.00, 0.53, and 0.69 for missing terms, respectively. CONCLUSION: We demonstrated a systematic approach that provides objective and accurate evidence guiding MetaMap configurations for optimizing performance. Combining objective evidence and the current practice of using principles, experience, and intuitions outperforms a single strategy in MetaMap configurations. Our methodology, reference codes, measurements, results, and workflow are valuable references for optimizing and configuring MetaMap.
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Mitotic rate is an important prognostic predictor in invasive breast carcinoma. Current guidelines recommend counting mitoses from 10 contiguous high power fields (HPFs) in the core biopsy. We propose a method to score mitotic activity in 1 HPF at the most mitotically active area of the tumour edge, or the interface between invasive tumour and benign breast tissue. We propose a score of 1, 2, or 3, corresponding to ≤1, 2, or ≥3 mitoses in 1 HPF, respectively. A total of 141 breast core biopsies with corresponding surgical excisions were blindly examined. We counted the number of mitotic figures in 1 HPF and in 10 contiguous HPFs in the core biopsy and compared with the mitotic count from 10 contiguous HPFs in the excision which is considered the gold standard. Concordance rates and interobserver agreement rates were calculated. The concordance rate was 82.3%, 78.7% and 82.3% between 1 HPF versus 10 HPFs in the core biopsy, 1 HPF in the core biopsy versus 10 HPFs in the excision and 10 HPFs in the core biopsy vs 10 HPFs in the excision, respectively. In the core biopsy, all three investigators agreed in 73.8% and 83.7% of the cases using the 1 HPF method and the 10 HPFs method, respectively; in the excision specimen, agreement was reached in 82.3% of the cases. The 1 HPF method showed similar concordance rate and interobserver agreement compared to the conventional method in the prediction of the mitotic score in the excision in all score groups. When stratified by mitotic score, the 1 HPF method predicted superior correlation with excision in the score 1 group than the 10 HPFs method, but not in the score 2 or 3 groups. From these findings we conclude that the proposed 1 HPF method can be used in clinical practice to grade invasive breast carcinomas in core biopsies, with the possibility of being utilised in small biopsies with less than 10 HPFs of invasive carcinoma.
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Neoplasias da Mama , Carcinoma Ductal de Mama , Prognóstico , Biópsia com Agulha de Grande Calibre , Mama/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Mitose , Gradação de TumoresRESUMO
Bile acids (BAs), produced in the liver and further transformed in the gut, are cholesterol-derived molecules involved in essential physiological processes. Recent studies suggest that BAs regulate T helper 17 cell function, but the underlying mechanism of this action and their therapeutic value in disease models remains unclear. Using an IL-23 minicircle DNA-based murine model of psoriasiform dermatitis, we showed that oral administration of secondary BAs, including lithocholic acid (LCA), deoxycholic acid, and 3-oxoLCA, significantly improved psoriasiform dermatitis without inducing apparent hepatotoxicity. Of the BAs tested, LCA possessed the greatest potency in treating psoriasiform dermatitis. Intravenous administration of LCA at a much lower dosage (compared with oral treatment) showed a comparable antipsoriatic effect and markedly suppressed the IL-17A response. Ex vivo experiments revealed that LCA reduced IL-17A production in IL-23-stimulated murine T cells in the absence of BA receptors TGR5 or FXR. Strikingly, BAs inhibited CCL20 expression in keratinocytes, which led to reduced migration of CCR6-expressing Jurkat cells cultured in the conditioned medium of stimulated keratinocytes. Thus, BAs improve psoriasiform dermatitis with minimal toxicity via direct inhibition of IL-17A production and blockade of CCL20-mediated trafficking, supporting the potential use of BAs in psoriasis.
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Eczema , Psoríase , Animais , Ácidos e Sais Biliares/uso terapêutico , Quimiocina CCL20 , Humanos , Interleucina-17/metabolismo , Interleucina-23 , Camundongos , Psoríase/tratamento farmacológico , Psoríase/metabolismo , Receptores CCR6RESUMO
Background The Lapidus procedure has become a popular procedure in correcting hallux valgus deformities and has undergone several modifications in an effort to improve the efficacy of the procedure. The senior author modifies this procedure with the addition of an intermetatarsal and intercuneiform fusion. Our hypothesis is that this will improve the procedure outcomes and decrease deformity recurrence. Methods We reviewed patient charts who underwent the procedure between 2014 and 2017 performed by the senior author. This yielded 47 reviewable cases, with 34 meeting study criteria. The cases were analyzed for standard hallux valgus measurements (intermetatarsal angle [IMA], hallux valgus angle [HVA]) and fusion on X-ray. Results The results of the study showed partial intermetatarsal and intercuneiform fusion failure in seven (20%) cases, and one case where the great toe fell into varus. These cases were excluded. In the remaining cases, there was a statistically significant improvement in the HVA and IMA between the preoperative X-ray and first postoperative X-ray. Additionally, there was no significant difference between HVA and IMA between first and final postoperative radiographs. There was a significant increase in IMA for the fusion failure cases (p=0.001). Conclusion Clinically, our findings demonstrate that successful union is possible with low recurrence and complication rates when using this modification of the Lapidus procedure in patients with hallux valgus deformity.
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BACKGROUND: Older adults display wide individual variability (heterogeneity) in the effects of resistance exercise training on muscle strength. The mechanisms driving this heterogeneity are poorly understood. Understanding of these mechanisms could permit development of more targeted interventions and/or improved identification of individuals likely to respond to resistance training interventions. Thus, this study assessed potential physiological factors that may contribute to strength response heterogeneity in older adults: neural activation, muscle hypertrophy, and muscle contractility. METHODS: In 24 older adults (72.3 ± 6.8 years), we measured the following parameters before and after 12 weeks of progressive resistance exercise training: i) isometric leg extensor strength; ii) isokinetic (60°/sec) leg extensor strength; iii) voluntary (neural) activation by comparing voluntary and electrically-stimulated muscle forces (i.e., superimposed doublet technique); iv) muscle hypertrophy via dual-energy x-ray absorptiometry (DXA) estimates of regional lean tissue mass; and v) intrinsic contractility by electrically-elicited twitch and doublet torques. We examined associations between physiological factors (baseline values and relative change) and the relative change in isometric and isokinetic muscle strength. RESULTS: Notably, changes in quadriceps contractility were positively associated with the relative improvement in isokinetic (r = 0.37-0.46, p ≤ 0.05), but not isometric strength (r = 0.09-0.21). Change in voluntary activation did not exhibit a significant association with the relative improvements in either isometric or isokinetic strength (r = 0.35 and 0.33, respectively; p > 0.05). Additionally, change in thigh lean mass was not significantly associated with relative improvement in isometric or isokinetic strength (r = 0.09 and -0.02, respectively; p > 0.05). Somewhat surprising was the lack of association between exercise-induced changes in isometric and isokinetic strength (r = 0.07). CONCLUSIONS: The strength response to resistance exercise in older adults appears to be contraction-type dependent. Therefore, future investigations should consider obtaining multiple measures of muscle strength to ensure that strength adaptations are comprehensively assessed. Changes in lean mass did not explain the heterogeneity in strength response for either contraction type, and the data regarding the influence of voluntary activation was inconclusive. For isokinetic contraction, the strength response was moderately explained by between-subject variance in the resistance-exercise induced changes in muscle contractility.
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Treinamento Resistido , Idoso , Exercício Físico , Humanos , Contração Isométrica , Contração Muscular , Força Muscular , Músculo EsqueléticoRESUMO
OBJECTIVE: To assess the involvement of the CCR6/CCL20 axis in psoriatic arthritis (PsA) and psoriasis (PsO) and to evaluate its potential as a therapeutic target. METHODS: First, we quantified CCL20 levels in peripheral blood and synovial fluid from PsA patients and examined the presence of CCR6+ cells in synovial and tendon tissue. Utilizing an interleukin-23 minicircle DNA (IL-23 MC) mouse model exhibiting key features of both PsO and PsA, we investigated CCR6 and CCL20 expression as well as the preventive and therapeutic effect of CCL20 blockade. Healthy tendon stromal cells were stimulated in vitro with IL-1ß to assess the production of CCL20 by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. The effect of conditioned media from stimulated tenocytes in inducing T cell migration was interrogated using a Transwell system. RESULTS: We observed an up-regulation of both CCR6 and CCL20 in the enthesis of IL-23 MC-treated mice, which was confirmed in human biopsy specimens. Specific targeting of the CCR6/CCL20 axis with a CCL20 locked dimer (CCL20LD) blocked entheseal inflammation, leading to profound reductions in clinical and proinflammatory markers in the joints and skin of IL-23 MC-treated mice. The stromal compartment in the tendon was the main source of CCL20 in this model and, accordingly, in vitro activated human tendon cells were able to produce this chemokine and to induce CCR6+ T cell migration, the latter of which could be blocked by CCL20LD. CONCLUSION: Our study highlights the pathogenic role of the CCR6/CCL20 axis in enthesitis and introduces the prospect of a novel therapeutic approach for treating patients with PsO and PsA.
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Artrite Psoriásica/metabolismo , Quimiocina CCL20/sangue , Inflamação/metabolismo , Líquido Sinovial/metabolismo , Animais , Artrite Psoriásica/sangue , Humanos , Inflamação/sangue , Interleucina-1beta/farmacologia , Interleucina-23/farmacologia , Camundongos , Pele/metabolismo , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Membrana Sinovial/metabolismo , Tendões/efeitos dos fármacos , Tendões/metabolismoRESUMO
We previously showed that exposure to a high-sugar and moderate-fat diet (i.e., Western diet [WD]) in mice induces appreciable skin inflammation and enhances the susceptibility to imiquimod-induced psoriasiform dermatitis, suggesting that dietary components may render the skin susceptible to psoriatic inflammation. In this study, utilizing an IL-23 minicircle-based model with features of both psoriasiform dermatitis and psoriatic arthritis, we showed that intake of WD for 10 weeks predisposed mice not only to skin but also to joint inflammation. Both WD-induced skin and joint injuries were associated with an expansion of IL-17Aâproducing γδ T cells and increased expression of T helper type 17 cytokines. After IL-23 minicircle delivery, WD-fed mice had reduced microbial diversity and pronounced dysbiosis. Treatment with broad-spectrum antibiotics suppressed IL-23âmediated skin and joint inflammation in the WD-fed mice. Strikingly, reduced skin and joint inflammation with a partial reversion of the gut microbiota were noted when mice switched from a WD to a standard diet after IL-23 minicircle delivery. These findings reveal that a short-term WD intakeâinduced dysbiosis is accompanied by enhanced psoriasis-like skin and joint inflammation. Modifications toward a healthier dietary pattern should be considered in patients with psoriatic skin and/or joint disease.
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Artrite Psoriásica/imunologia , Dieta Ocidental/efeitos adversos , Disbiose/imunologia , Microbioma Gastrointestinal/imunologia , Psoríase/imunologia , Animais , Artrite Psoriásica/microbiologia , Artrite Psoriásica/prevenção & controle , Modelos Animais de Doenças , Disbiose/microbiologia , Humanos , Imiquimode/administração & dosagem , Imiquimode/imunologia , Interleucina-23/metabolismo , Camundongos , Psoríase/microbiologia , Psoríase/prevenção & controle , Transdução de Sinais/imunologiaRESUMO
BACKGROUND: Sorensen Test time-to-task-failure (TTF) predicts several low back pain (LBP) clinical outcomes, including recurrence. Because the test is described as a measure of trunk extensor (TE) muscle endurance, LBP rehabilitation programs often emphasize endurance training, but the direct role of TE muscle function on Sorensen Test-TTF remains unclear. OBJECTIVE: To assess the discriminative and associative properties of multiple markers of isolated TE performance with regard to Sorensen Test-TTF in individuals with recurrent LBP. METHOD: Secondary analysis of baseline measures from participants in a registered (NCT02308189) trial (10 men; 20 women) was performed. Participants were classified by Sorensen Test-TTF as high, moderate or low risk for subsequent LBP episodes, and compared to determine if classification could discriminate differences in TE function. Correlations between Sorensen Test-TTF and isolated TE performance, anthropometrics and disability were investigated. RESULTS: Individuals at risk of subsequent LBP episodes had greater perceived disability and fat mass/TE strength ratios (P⩽ 0.05) than those not at risk. Modest, significant (r= 0.36-0.42, P⩽ 0.05) associations were found between Sorensen Test-TTF, TE endurance and fat mass/TE strength. Exploratory analyses suggested possible sex-specific differences related to Sorensen Test-TTF. CONCLUSIONS: Isolated TE muscle endurance is only one of several factors with similar influence on Sorensen Test-TFF, thus LBP rehabilitation strategies should consider other factors, including TE strength, anthropometrics and perceived disability.
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Contração Isométrica/fisiologia , Dor Lombar/fisiopatologia , Força Muscular/fisiologia , Músculo Esquelético/fisiopatologia , Resistência Física/fisiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fadiga Muscular/fisiologia , Recidiva Local de Neoplasia/fisiopatologia , Tronco/fisiopatologia , Adulto JovemRESUMO
Background Foot and ankle surgeries are frequently accompanied by a peripheral nerve block in order to reduce postoperative pain. Higher than expected complication rates with peripheral nerve blocks have led to increased concern among surgeons and patients. To our knowledge, no study conducted by the treating surgeon has identified risk factors that may predispose a patient to complications. Our goal was to attempt to identify those risk factors. Methods We reviewed patient charts of those who underwent an orthopedic foot and ankle procedure between 2013 and 2018, as performed by the senior author. This yielded 992 procedures performed across four surgical locations. Of these procedures, 137 procedures were removed because no block was used. The remaining cases were analyzed for nerve complications, defined as sensory or motor deficits along the distribution of a nerve. The patients were divided into those with and without complications and were evaluated for differences. Statistical analysis was performed using the SAS® software (SAS Institute Inc., Cary, North Carolina, USA). Results The overall short-term complication rate was 10.1% and the long-term complication rate was 4.3%, with a total of 855 blocks given. Electromyographies (EMGs) were performed on 24.4% of the patients with a complication. Of the EMGs, 95.2% confirmed nerve complications in the distribution of the blocked nerve. The significant factors associated with complications were age, BMI, location, and smoking status. A regression analysis was performed to determine the odds ratio for individual factors. Those with significantly higher odds ratio were between 40 and 65 years of age, had normal or underweight BMI, underwent surgery at an outpatient surgery center, and were current smokers. Conclusions Our study suggests that there are significant epidemiological factors in predicting postoperative complications related to a peripheral nerve block. The study also shows a similar short-term complication rate but a higher long-term complication rate than other studies. This data are important because it allows for an informed decision to be made between a surgeon, anesthesiologist, and the patient regarding the safety and necessity of delivering a preoperative peripheral nerve block based on patient risk factors.
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CCR6 is important for the trafficking of IL-17A-producing γδ T cells and required for the development of psoriasiform dermatitis in an IL-23 intradermal injection model. The role of CCR6, however, in IL-23-mediated joint inflammation is unclear. We herein hydrodynamically delivered IL-23 minicircle DNA into wild-type and CCR6-deficient (CCR6-knockout) mice to induce overexpression of IL-23 systemically. After IL-23 gene transfer, wild-type mice exhibited concurrent skin and joint changes that recapitulate some features found in human psoriatic skin and joints. CCR6-knockout mice were resistant to IL-23-induced skin inflammation but exhibited no changes in joint inflammation compared with wild-type mice. Depletion of neutrophils protected wild-type mice from skin and joint disease without suppressing T helper type 17 cytokine expression. In contrast, mice lacking γδ T cells showed a partial reduction in neutrophilic recruitment and a significant decrease in IL-17A expression in skin and paw tissue. Thus, in an IL-23-mediated model that allows concurrent assessment of both skin and joint disease, we showed that CCR6 is critical for inflammation in the skin but not in the joint. Furthermore, our data suggest that neutrophils and γδ T cells are key effector cells in IL-23-mediated skin and joint inflammation in mice.