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BACKGROUND: Changing the course duration or timing of subjects in learning pathways would influence medical students' learning outcomes. Curriculum designers need to consider the strategy of reducing cognitive load and evaluate it continuously. Our institution underwent gradual curricular changes characterized by reducing cognitive load since 2000. Therefore, we wanted to explore the impact of this strategy on our previous cohorts. METHODS: This cohort study explored learning pathways across academic years of more than a decade since 2000. Eight hundred eighty-two medical students between 2006 and 2012 were included eventually. Learning outcomes included an average and individual scores of subjects in different stages. Core subjects were identified as those where changes in duration or timing would influence learning outcomes and constitute different learning pathways. We examined whether the promising learning pathway defined as the pathway with the most features of reducing cognitive load has higher learning outcomes than other learning pathways in the exploring dataset. The relationship between features and learning outcomes was validated by learning pathways selected in the remaining dataset. RESULTS: We found nine core subjects, constituting four different learning pathways. Two features of extended course duration and increased proximity between core subjects of basic science and clinical medicine were identified in the promising learning pathway 2012, which also had the highest learning outcomes. Other pathways had some of the features, and pathway 2006 without such features had the lowest learning outcomes. The relationship between higher learning outcomes and cognitive load-reducing features was validated by comparing learning outcomes in two pathways with and without similar features of the promising learning pathway. CONCLUSION: An approach to finding a promising learning pathway facilitating students' learning outcomes was validated. Curricular designers may implement similar design to explore the promising learning pathway while considering potential confounding factors, including students, medical educators, and learning design of the course.
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Cognición , Aprendizaje , Humanos , Estudios de Cohortes , Estudiantes de Medicina/psicología , Curriculum , Femenino , MasculinoRESUMEN
BACKGROUND: Interleukin-17 (IL-17) is a pro-inflammatory cytokine that plays a vital role in the promotion of tumorigenesis in various cancers, including colorectal cancer (CRC). Based on current evidence, IL-17 binds to interleukin-17 receptor A (IL-17RA); however, the role of IL-17RA has not been elucidated in previous studies on CRC. In this study, we explored the role of IL-17RA in human CRC tissues and the progression of CRC in humans and mice. METHODS: The expressions of IL-17RA and epithelial-mesenchymal transition (EMT)-related genes were examined in CRC cells and tissue samples by quantitative real-time polymerase chain reaction. The role of IL-17RA in pathogenesis and prognosis was evaluated using a Chi-squared test, Kaplan-Meier analysis, univariate, and multivariate Cox regression analysis in 133 CRC patients. A tumor-bearing mice model was executed to evaluate the role of IL-17RA in tumor growth, vascularity and population of infiltrating immune cells. RESULTS: IL-17RA expression was found to be significantly higher in CRC tissues than in adjacent normal tissues. The expression of IL-17RA in Stage IV patients was significantly higher than that in Stages I and II patients. Patients with high IL-17RA expression exhibited significantly worse overall and CRC-specific survival than those with low IL-17RA expression. Functional assessment suggested that the knockdown of IL-17RA expression distinctly suppressed cellular proliferation, migration, invasion, and EMT-related gene expression. In a tumor-bearing mouse model, decreased IL-17RA expression significantly repressed tumor growth and vascularity and reduced the population of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). CONCLUSION: Reduced IL-17RA expression also suppressed cellular proliferation, migration, and invasion, and the expression of EMT genes. Knockdown of IL-17RA inhibited tumor growth and vascularity and decreased the population of Tregs and MDSCs in mouse tumors. Overall, IL-17RA expression was identified to be independently associated with the prognosis of patients with CRC.
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Neoplasias Colorrectales , Interleucina-17 , Animales , Humanos , Ratones , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales/patología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Interleucina-17/genética , Interleucina-17/metabolismo , PronósticoRESUMEN
AIMS: This study aims to ascertain dementia incidence from 2004 to 2017 in Taiwan, and to examine the disease course in comorbidity, treatments, healthcare usage, and mortality among older people with incident dementia preceding the diagnosis of dementia and afterwards. METHODS: Taiwan National Health Insurance data on people aged ≥ 65 years with incident dementia from January 2004 to December 2017 were excerpted to estimate annual incidence rates and annualized percentage changes(APCs). For people diagnosed before 2013, annual mortality rates and causes of death during 5-years' follow-up were determined. Changes in 22 diseases/conditions, hospital visits and admissions, and psychotropic medication prescriptions commonly associated with dementia, were examined from 3 years preceding the index diagnosis until 5 years afterwards. RESULTS: From 2004 to 2017, the annual incidence of dementia in Taiwan increased from 30,606 to 50,651, and by > 90 % in women; age-standardized annual incidence increased significantly, with an APC of 0.4 %(p = 0.02). For 372,203 incident cases from 2004 to 2013, annual mortality wasâ¼12 % during 5-years' follow-up. The prevalence of most comorbidities increased by 65-150 % after being diagnosed with dementia. People with incident dementia had increased healthcare usage 1 year before diagnosis, which peaked 1 year afterwards. Psychotropic medication prescriptions increased gradually over 3 years before diagnosis, peaked 3 months afterwards, gradually declined during the next 2 years, then remained stable. CONCLUSION: The incidence of dementia in Taiwan has increased gradually over time, with an annual mortality risk ofâ¼12 %. Older people with dementia had more healthcare needs and comorbid conditions after dementia diagnosis, highlighting the exigency of person-centered dementia care.
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Demencia , Humanos , Femenino , Anciano , Incidencia , Estudios de Cohortes , Taiwán/epidemiología , Comorbilidad , Demencia/tratamiento farmacológico , Demencia/epidemiología , Atención a la Salud , Aceptación de la Atención de SaludRESUMEN
High-sugar diets (HSDs) often lead to obesity and type 2 diabetes, both metabolic syndromes associated with stem cell dysfunction. However, it is unclear whether excess dietary sugar affects stem cells. Here, we report that HSD impairs stem cell function in the intestine and ovaries of female Drosophila prior to the onset of insulin resistance, a hallmark of type 2 diabetes. Although 1â week of HSD leads to obesity, impaired oogenesis and altered lipid metabolism, insulin resistance does not occur. HSD increases glucose uptake by germline stem cells (GSCs) and triggers reactive oxygen species-induced JNK signaling, which reduces GSC proliferation. Removal of excess sugar from the diet reverses these HSD-induced phenomena. A similar phenomenon is found in intestinal stem cells (ISCs), except that HSD disrupts ISC maintenance and differentiation. Interestingly, tumor-like GSCs and ISCs are less responsive to HSD, which may be because of their dependence on glycolytic metabolism and high energy demand, respectively. This study suggests that excess dietary sugar induces oxidative stress and damages stem cells before insulin resistance develops, a mechanism that may also occur in higher organisms.
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Células Madre Adultas , Diabetes Mellitus Tipo 2 , Proteínas de Drosophila , Resistencia a la Insulina , Animales , Femenino , Drosophila/metabolismo , Proteínas de Drosophila/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Azúcares de la Dieta/metabolismo , Células Madre Adultas/metabolismo , Células Madre Neoplásicas/metabolismo , ObesidadRESUMEN
1,2-diacetylbenzene (1,2-DAB) is a neurotoxic component of aromatic solvents commonly used in industrial applications that induces neuropathological changes in animals. This study unraveled the toxic impact of 1,2-DAB in nerve tissues, explant cultures, and neuron-glial cultures, and explored whether herbal products can mitigate its toxicity. The effects of DAB on axonal transport were studied in retinal explant cultures grown in a micro-patterned dish. The mitochondrial movement in the axons was captured using time-lapse video recordings. The results showed that 1,2-DAB, but not 1,3-DAB inhibited axonal outgrowth and mitochondrial movement in a dose-dependent manner. The toxicity of 1,2-DAB was further studied in spinal cord tissues and cultures. 1,2-DAB selectively induced modifications of microtubules and neurofilaments in spinal cord tissues. 1,2-DAB also potently induced cell damage in both neuronal and glial cultures. Further, 1,2-DAB-induced cellular ATP depletion precedes cell damage in glial cells. Interestingly, treatment with the herbal products silibinin or silymarin effectively mitigated 1,2-DAB-induced toxicity in spinal cord tissues and neuronal/glial cultures. Collectively, the molecular toxicity of 1,2-DAB in neural tissues involves protein modification, ATP depletion, and axonal transport defects, leading to cell death. Silibinin and silymarin show promising neuroprotective effects against 2-DAB-induced toxicity.
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Neuronas , Silimarina , Animales , Silibina , Adenosina TrifosfatoRESUMEN
Electronic cigarettes have rapidly gained acceptance recently. Nicotine-containing electronic cigarette liquids (e-liquids) are prohibited in some countries, but are permitted and simply available online in others. A rapid detection method is therefore required for on-site inspection or screening of a large amount of samples. Our previous study demonstrated a surface-enhanced Raman scattering (SERS)-based approach to identify nicotine-containing e-liquids; without any pre-treatment, e-liquid can be directly tested on our solid-phase SERS substrates, made of silver nanoparticle arrays embedded in anodic aluminium oxide nanochannels (Ag/AAO). However, this approach required manual determination of spectral signatures and negative samples should be validated in the second round detection. Here, after examining 406 commercial e-liquids, we refined this approach by developing artificial intelligence (AI)-assisted spectrum interpretations. We also found that nicotine and benzoic acid can be simultaneously detected in our platform. This increased test sensitivity because benzoic acid is usually used in nicotine salts. Around 64% of nicotine-positive samples in this study showed both signatures. Using either cutoffs of nicotine and benzoic acid peak intensities or a machine learning model based on the CatBoost algorithm, over 90% of tested samples can be correctly discriminated with only one round of SERS measurement. False negative and false positive rates were 2.5-4.4% and 4.4-8.9%, respectively, depending on the interpretation method and thresholds applied. The new approach takes only 1 microliter of sample and can be performed in 1-2 min, suitable for on-site inspection with portable Raman detectors. It could also be a complementary platform to reduce samples that need to be analyzed in the central labs and has the potential to identify other prohibited additives.
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Sistemas Electrónicos de Liberación de Nicotina , Nanopartículas del Metal , Nicotina , Espectrometría Raman , Inteligencia Artificial , Ácido Benzoico , PlataRESUMEN
The adipose tissue is a central metabolic organ that regulates whole-body energy homeostasis. The abnormal expansion of adipose tissue leads to the progression of obesity. The adipose tissue microenvironment is affected by pathological hypertrophy of adipocytes, highly correlated with systemic metabolic disorders. In vivo genetic modification is a great tool for understanding the role of genes involved in such processes. However, obtaining new conventional engineered mice is time consuming and costly. Here, we provide a simple and speedy method to efficiently transduce genes into adipose tissue by injecting the adeno-associated virus vector serotypes 8 (AAV8) into the fat pads of adult mice.
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Circulating tumor cells (CTCs) in blood are accepted as a prognostic marker for patients with metastatic colorectal cancer (CRC). However, there is limited data on the use of CTCs as a prognostic marker for non-metastatic patients. In the current study, we used a rare cell automated analysis platform, the MiSelect R System, to enumerate CTCs from blood in non-metastatic CRC patients, and corelated the number of CTCs with the clinical staging and survival. The presence of CTCs in mesenteric vein blood (MVB) samples from 101 CRC patients was significantly associated with T stage. Patients with 1 or more CTCs per 8 mL of MVB exhibited significantly worse disease-free survival (DFS) and cancer-specific survival (CSS) compared to patient without CTCs. The presence of CTCs before surgery is an independent marker for both DFS and CSS. CTC presence after surgical resection is also a prognostic marker. CTCs are a potentially useful prognostic and predictive biomarker in non-metastatic CRC patients that may further stratify patient's risk status within different stages of disease.
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Neoplasias del Colon , Neoplasias Colorrectales , Células Neoplásicas Circulantes , Neoplasias del Recto , Humanos , Neoplasias Colorrectales/patología , Pronóstico , Células Neoplásicas Circulantes/patología , Biomarcadores de TumorRESUMEN
BACKGROUND: Circulating tumor cells (CTCs) have been investigated as a potential biomarker for predicting prognosis and monitoring therapeutic responses in colorectal cancer (CRC). However, the sensitivity of CTCs detection is low, thus limiting the clinical utility of CTCs. We aim to examine the clinicopathological parameters that improve prognosis prediction for CRC using CTCs as a biomarker. METHODS: We enumerated CTCs in 186 CRC patients and associated the number of CTCs with the clinicopathological features and overall survival (OS) using a univariate and multivariate Cox regression model and Kaplan-Meier survival analysis. RESULTS: The presence of CTCs from 186 CRC patients was significantly associated with stage, preoperational carcinoembryonic antigen (CEA), and CA19-9 levels. Using Kaplan-Meier survival and Cox regression analysis, patients with five or more CTCs exhibited significantly worse OS compared to patients with fewer than five CTCs. The combination of CTCs with tumor marker CEA has a better OS prediction than individual CTCs or CEA and serves as a more effective prediction model in patients with CRC. CONCLUSION: We identified that patients with more than five CTCs exhibited significantly worse OS. Additionally, patients with the normal level of CEA, but who also had more than five CTCs trended towards a worse OS.
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Neoplasias Colorrectales , Células Neoplásicas Circulantes , Humanos , Pronóstico , Antígeno Carcinoembrionario , Células Neoplásicas Circulantes/patología , Biomarcadores de TumorRESUMEN
Tumor necrosis factor (TNF)-α is a proinflammatory cytokine involved in the pathogenesis of sarcopenia, but its short half-life and inconsistent reproducibility limit the potential of TNF-α to be an ideal sarcopenia biomarker. Anti-TNF-α, a natural consequent autoantibody to TNF-α, is an indicator of relatively prolonged TNF-α exposure, has more stable concentrations than TNF-α and should be a better alternative as a biomarker of sarcopenia. Data from 484 participants from the I-Lan Longitudinal Aging Study were used for this study, and sarcopenia was defined by the Asian Working Group for Sarcopenia 2019 consensus. Plasma levels of anti-TNF-α were determined by a sandwich ELISA approach, and levels of TNF-α were determined by an immunoassay. Compared to nonsarcopenic participants, 43 sarcopenic participants had higher levels of anti-TNF-α (0.73 ± 0.19 vs. 0.79 ± 0.25 OD, p = 0.045). Plasma levels of anti-TNF-α were positively correlated with TNF-α (r = 0.24, p < 0.001), and plasma levels of anti-TNF-α were positively correlated with adiposity (r = 0.16, p < 0.001) and negatively correlated with lean body mass (r = -0.14, p = 0.003). Individuals with increasing levels of anti-TNF-α had higher odds of being sarcopenic (OR 5.4, 95 % CI: 1.1-25.8, p = 0.035), and these associations were stronger among women and younger adults. An association between TNF-α and sarcopenia was noted only in middle-aged adults (OR 6.2, 95 % CI: 1.8-21.7, p = 0.004). Plasma anti-TNF-α levels were positively correlated with TNF-α and were significantly associated with sarcopenia. Anti-TNF-α may be a more appropriate biomarker than TNF-α for sarcopenia, but further investigations are needed to confirm its roles in sarcopenia diagnosis and treatment response evaluation.
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Sarcopenia , Femenino , Humanos , Persona de Mediana Edad , Envejecimiento , Biomarcadores , Necrosis/complicaciones , Reproducibilidad de los Resultados , Inhibidores del Factor de Necrosis Tumoral , Factor de Necrosis Tumoral alfa/inmunología , AutoanticuerposRESUMEN
Recent studies have shown that mitochondrial morphology can modulate organelle function and greatly affect stem cell behavior, thus affecting tissue homeostasis. As such, we previously showed that the accumulation of fragmented mitochondria in aged Drosophila ovarian germline stem cells (GSCs) contributes to age-dependent GSC loss. However, standard immunofluorescence methods to examine mitochondrial morphology yield images with insufficient resolution for rigorous analysis, while 3-dimensional electron microscopy examination of mitochondrial morphology is labor intensive and allows only limited sampling of mitochondria. To overcome these issues, we utilized the expansion microscopy technique to expand GSC samples by 4-fold in combination with mitochondrial immunofluorescence labeling. Here, we present a simple, inexpensive method for nanoscale optical imaging of mitochondria in the germline. This protocol may be beneficial for studies that require visualization of mitochondria or other fine subcellular structures in the Drosophila ovary.
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Proteínas de Drosophila , Células Madre Oogoniales , Animales , Femenino , Drosophila , Microscopía , MitocondriasRESUMEN
Regulation of fatty acid uptake, lipid production and storage, and metabolism of lipid droplets (LDs), is closely related to lipid homeostasis, adipocyte hypertrophy and obesity. We report here that stomatin, a major constituent of lipid raft, participates in adipogenesis and adipocyte maturation by modulating related signaling pathways. In adipocyte-like cells, increased stomatin promotes LD growth or enlargements by facilitating LD-LD fusion. It also promotes fatty acid uptake from extracellular environment by recruiting effector molecules, such as FAT/CD36 translocase, to lipid rafts to promote internalization of fatty acids. Stomatin transgenic mice fed with high-fat diet exhibit obesity, insulin resistance and hepatic impairments; however, such phenotypes are not seen in transgenic animals fed with regular diet. Inhibitions of stomatin by gene knockdown or OB-1 inhibit adipogenic differentiation and LD growth through downregulation of PPARγ pathway. Effects of stomatin on PPARγ involves ERK signaling; however, an alternate pathway may also exist.
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Adipogénesis , Gotas Lipídicas , Adipogénesis/genética , Animales , Antígenos CD36/genética , Antígenos CD36/metabolismo , Dieta Alta en Grasa , Ácidos Grasos/metabolismo , Gotas Lipídicas/metabolismo , Metabolismo de los Lípidos , Sistema de Señalización de MAP Quinasas , Ratones , Obesidad/genética , Obesidad/metabolismo , PPAR gamma/genética , PPAR gamma/metabolismoRESUMEN
Morphogen-mediated signaling is critical for proper organ development and stem cell function, and well-characterized mechanisms spatiotemporally limit the expression of ligands, receptors, and ligand-binding cell-surface glypicans. Here, we show that in the developing Drosophila ovary, canonical Wnt signaling promotes the formation of somatic escort cells (ECs) and their protrusions, which establish a physical permeability barrier to define morphogen territories for proper germ cell differentiation. The protrusions shield germ cells from Dpp and Wingless morphogens produced by the germline stem cell (GSC) niche and normally only received by GSCs. Genetic disruption of EC protrusions allows GSC progeny to also receive Dpp and Wingless, which subsequently disrupt germ cell differentiation. Our results reveal a role for canonical Wnt signaling in specifying the ovarian somatic cells necessary for germ cell differentiation. Additionally, we demonstrate the morphogen-limiting function of this physical permeability barrier, which may be a common mechanism in other organs across species.
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BACKGROUND: The extent of interstitial fibrosis in the kidney not only correlates with renal function at the time of biopsy but also predicts future renal outcome. However, its assessment by pathologists lacks good agreement. The aim of this study is to construct a machine learning-based model that enables automatic and reliable assessment of interstitial fibrosis in human kidney biopsies. METHODS: Validated cortex, glomerulus and tubule segmentation algorithms were incorporated into a single model to assess the extent of interstitial fibrosis. The model performances were compared with expert renal pathologists and correlated with patients' renal functional data. RESULTS: Compared with human raters, the model had the best agreement [intraclass correlation coefficient (ICC) 0.90] to the reference in 50 test cases. The model also had a low mean bias and the narrowest 95% limits of agreement. The model was robust against colour variation on images obtained at different times, through different scanners, or from outside institutions with excellent ICCs of 0.92-0.97. The model showed significantly better test-retest reliability (ICC 0.98) than humans (ICC 0.76-0.94) and the amount of interstitial fibrosis inferred by the model strongly correlated with 405 patients' serum creatinine (r = 0.65-0.67) and estimated glomerular filtration rate (r = -0.74 to -0.76). CONCLUSIONS: This study demonstrated that a trained machine learning-based model can faithfully simulate the whole process of interstitial fibrosis assessment, which traditionally can only be carried out by renal pathologists. Our data suggested that such a model may provide more reliable results, thus enabling precision medicine.
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Riñón , Aprendizaje Automático , Humanos , Creatinina , Fibrosis , Reproducibilidad de los Resultados , Riñón/patología , BiopsiaRESUMEN
Polarized or precision targeting of protein complexes to their destinations is fundamental to cellular homeostasis, but the mechanism underpinning directional protein delivery is poorly understood. Here, we use the uropod targeting HIV synapse as a model system to show that the viral assembly machinery Gag is copolarized with the intracellular calcium (Ca2+) gradient and binds specifically with Ca2+. Conserved glutamic/aspartic acids flanking endosomal sorting complexes required for transport binding motifs are major Ca2+ binding sites. Deletion or mutation of these Ca2+ binding residues resulted in altered protein trafficking phenotypes, including (i) changes in the Ca2+-Gag distribution relationship during uropod targeting and/or (ii) defects in homo/hetero-oligomerization with Gag. Mutation of Ca2+ binding amino acids is associated with enhanced ubiquitination and a decline in virion release via uropod protein complex delivery. Our data that show Ca2+-protein binding, via the intracellular Ca2+ gradient, represents a mechanism that regulates intracellular protein trafficking.
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PURPOSE: The study aims to investigate long-term psychological distress and its risk factors in the burn survivors. DESIGN: A longitudinal study with follow-up interviews was conducted from November 2015-June 2018. A post-burn baseline interview was conducted 6 months after the event, followed by annual surveys for three years. METHODS: The burn survivors received structured assessment through telephone in the four-wave interviews, including the five-item Brief Symptom Rating Scale (BSRS-5); two-item Patient Health Questionnaire (PHQ-2); four-item Startle, Physiological Arousal, Anger, and Numbness Scale (SPAN-4); and six-item Impact of Event Scale (IES-6) alongside demographic data and other health-related assessment. FINDINGS: A total of 180 respondents with the mean age of 23 years old completed the four waves of interview. Using the BSRS-5 as the outcome, each variable had different input in psychological distress during the follow-up years. The main finding was that the SPAN-4 score could predict more than 62% of psychological distress between 6 months and 3 years after the disaster. The generalized estimating equation demonstrated that SPAN-4, IES-6, family functioning impairment, hypnotics use, adaptation to the event, and PHQ-2 could predict psychological distress. However, the variable of follow-up year did not exemplify significant estimation in the model. CONCLUSIONS: The results indicated that different factors had various influences on psychological distress across the four follow-up stages. PTSD-like symptoms, depression, and anxiety were the most common psychological problems experienced by the young burn cohort in the longitudinal post-traumatic period. CLINICAL RELEVANCE: Healthcare providers should be aware of psychological consequences of traumatic events within up to a 3-year post-burn period, particularly post-traumatic stress, depression, and anxiety symptoms.
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Desastres , Distrés Psicológico , Trastornos por Estrés Postraumático , Adulto , Estudios de Cohortes , Humanos , Estudios Longitudinales , Trastornos por Estrés Postraumático/etiología , Trastornos por Estrés Postraumático/psicología , Estrés Psicológico , Sobrevivientes/psicología , Taiwán , Adulto JovenRESUMEN
Background: Drug repurposing is a fast and effective way to develop drugs for an emerging disease such as COVID-19. The main challenges of effective drug repurposing are the discoveries of the right therapeutic targets and the right drugs for combating the disease. Methods: Here, we present a systematic repurposing approach, combining Homopharma and hierarchal systems biology networks (HiSBiN), to predict 327 therapeutic targets and 21,233 drug-target interactions of 1,592 FDA drugs for COVID-19. Among these multi-target drugs, eight candidates (along with pimozide and valsartan) were tested and methotrexate was identified to affect 14 therapeutic targets suppressing SARS-CoV-2 entry, viral replication, and COVID-19 pathologies. Through the use of in vitro (EC50 = 0.4 µM) and in vivo models, we show that methotrexate is able to inhibit COVID-19 via multiple mechanisms. Results: Our in vitro studies illustrate that methotrexate can suppress SARS-CoV-2 entry and replication by targeting furin and DHFR of the host, respectively. Additionally, methotrexate inhibits all four SARS-CoV-2 variants of concern. In a Syrian hamster model for COVID-19, methotrexate reduced virus replication, inflammation in the infected lungs. By analysis of transcriptomic analysis of collected samples from hamster lung, we uncovered that neutrophil infiltration and the pathways of innate immune response, adaptive immune response and thrombosis are modulated in the treated animals. Conclusions: We demonstrate that this systematic repurposing approach is potentially useful to identify pharmaceutical targets, multi-target drugs and regulated pathways for a complex disease. Our findings indicate that methotrexate is established as a promising drug against SARS-CoV-2 variants and can be used to treat lung damage and inflammation in COVID-19, warranting future evaluation in clinical trials.
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COVID-19 , SARS-CoV-2 , Animales , Cricetinae , Metotrexato/farmacología , Metotrexato/uso terapéutico , Antivirales/farmacología , Antivirales/uso terapéutico , Inflamación/tratamiento farmacológico , Biología ComputacionalRESUMEN
Tuberculosis caused by Mycobacterium tuberculosis complex (MTBC) is one of the major infectious diseases in the world. Identification of MTBC and differential diagnosis of nontuberculous mycobacteria (NTM) species impose challenges because of their taxonomic similarity. This study describes a differential diagnosis method using the surface-enhanced Raman scattering (SERS) measurement of molecules released by Mycobacterium species. Conventional principal component analysis and linear discriminant analysis methods successfully separated the acquired spectrum of MTBC from those of NTM species but failed to distinguish between the spectra of different NTM species. A novel sensible functional linear discriminant analysis (SLDA), projecting the averaged spectrum of a bacterial specie to the subspace orthogonal to the within-species random variation, thereby eliminating its influence in applying linear discriminant analysis, was employed to effectively discriminate not only MTBC but also species of NTM. The successful demonstration of this SERS-SLDA method opens up new opportunities for the rapid differentiation of Mycobacterium species.
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Infecciones por Mycobacterium no Tuberculosas , Mycobacterium tuberculosis , Tuberculosis , Análisis Discriminante , Humanos , Micobacterias no TuberculosasRESUMEN
BACKGROUND: Metabolic syndrome has been shown to be a risk for new onset of cardiovascular disease (CVD) and type 2 diabetes. The subclasses of metabolic syndrome and any associated adverse health outcomes remain obscure. This study aimed to explore potential subtypes of metabolic syndrome, their associations with incidental diabetes, and any Major Adverse Cardiovascular Events (MACE). METHODS: Data for the retrospective cohort study were extracted from the New Taipei City Elderly Health Examination Database in the years 2014 and 2016. Demographic data, status of metabolic syndrome, its components, and latent class analysis (LCA) were analyzed. All participants were aged 65 years and older, with those having a prior history of CVD, cerebrovascular disease, diabetes mellitus (DM), and currently taking medications for hypertension, diabetes, and dyslipidemia were excluded. RESULTS: A total of 4,537 senior citizens were enrolled, with 2,207 (48.6%) of them identified as men. The prevalence of both metabolic syndrome and central obesity was increased with age. A 4-latent class model was fitted for participants diagnosed with metabolic syndrome. The central obesity (ABD)+ hyperglycemia (GLU)+ reduced HDL-C (HDL)+ high Blood Pressure (BP) group displayed the highest hazard ratio (HR) for predicting the new onset of diabetes, while the ABD+HDL+BP group showed a high risk for both CVD and MACE when compared after 2 years of follow-up. CONCLUSIONS: This epidemiological analysis demonstrated that the risks of developing new-onset diabetes, CVD, and MACE varied among the different subtypes of metabolic syndrome.