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BACKGROUND AND AIMS: Chronic non-cancer pain (CNCP) is one of the most common causes of disability globally. Opioid prescribing to treat CNCP remains widespread, despite limited evidence of long-term clinical benefit and evidence of harm such as problematic pharmaceutical opioid use (POU) and overdose. The study aimed to measure the prevalence of POU in CNCP patients treated with opioid analgesics. METHOD: A comprehensive systematic literature review and meta-analysis was undertaken using MEDLINE, Embase and PsycINFO databases from inception to 27 January 2021. We included studies from all settings with participants aged ≥ 12 with non-cancer pain of ≥ 3 months duration, treated with opioid analgesics. We excluded case-control studies, as they cannot be used to generate prevalence estimates. POU was defined using four categories: dependence and opioid use disorder (D&OUD), signs and symptoms of D&OUD (S&S), aberrant behaviour (AB) and at risk of D&OUD. We used a random-effects multi-level meta-analytical model. We evaluated inconsistency using the I2 statistic and explored heterogeneity using subgroup analyses and meta-regressions. RESULTS: A total of 148 studies were included with > 4.3 million participants; 1% of studies were classified as high risk of bias. The pooled prevalence was 9.3% [95% confidence interval (CI) = 5.7-14.8%; I2 = 99.9%] for D&OUD, 29.6% (95% CI = 22.1-38.3%, I2 = 99.3%) for S&S and 22% (95% CI = 17.4-27.3%, I2 = 99.8%) for AB. The prevalence of those at risk of D&OUD was 12.4% (95% CI = 4.3-30.7%, I2 = 99.6%). Prevalence was affected by study setting, study design and diagnostic tool. Due to the high heterogeneity, the findings should be interpreted with caution. CONCLUSIONS: Problematic pharmaceutical opioid use appears to be common in chronic pain patients treated with opioid analgesics, with nearly one in 10 experiencing dependence and opioid use disorder, one in three showing signs and symptoms of dependence and opioid use disorder and one in five showing aberrant behaviour.
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Medical advances prolonging life have led to more permanent pacemaker implants. When pacemaker implantation (PMI) is commonly caused by sick sinus syndrome or conduction disorders, predicting PMI is challenging, as patients often experience related symptoms. This study was designed to create a deep learning model (DLM) for predicting future PMI from ECG data and assess its ability to predict future cardiovascular events. In this study, a DLM was trained on a dataset of 158,471 ECGs from 42,903 academic medical center patients, with additional validation involving 25,640 medical center patients and 26,538 community hospital patients. Primary analysis focused on predicting PMI within 90 days, while all-cause mortality, cardiovascular disease (CVD) mortality, and the development of various cardiovascular conditions were addressed with secondary analysis. The study's raw ECG DLM achieved area under the curve (AUC) values of 0.870, 0.878, and 0.883 for PMI prediction within 30, 60, and 90 days, respectively, along with sensitivities exceeding 82.0% and specificities over 81.9% in the internal validation. Significant ECG features included the PR interval, corrected QT interval, heart rate, QRS duration, P-wave axis, T-wave axis, and QRS complex axis. The AI-predicted PMI group had higher risks of PMI after 90 days (hazard ratio [HR]: 7.49, 95% CI: 5.40-10.39), all-cause mortality (HR: 1.91, 95% CI: 1.74-2.10), CVD mortality (HR: 3.53, 95% CI: 2.73-4.57), and new-onset adverse cardiovascular events. External validation confirmed the model's accuracy. Through ECG analyses, our AI DLM can alert clinicians and patients to the possibility of future PMI and related mortality and cardiovascular risks, aiding in timely patient intervention.
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Doenças Cardiovasculares , Aprendizado Profundo , Eletrocardiografia , Marca-Passo Artificial , Humanos , Eletrocardiografia/métodos , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Inteligência Artificial , Síndrome do Nó SinusalRESUMO
This study integrated sample partition, incubation, and continuous fluorescence detection on a single microfluidic chip for droplet-based digital Loop-Mediated Isothermal Amplification (LAMP) of nucleic acids. This integration eliminated the need to transfer reactions between different platforms, avoiding sample contamination and loss. Prior to the reaction, filling the channels with an oil phase and adding a glass cover slip on top of the chip overcame the problem of bubble generation in the channels during the LAMP reaction due to heating. Additionally, using two fluorescence intensity thresholds enabled simultaneous detection and counting of positive and negative droplets within a single fluorescence detection channel. The chip can partition approximately 6000 droplets from a 5 µL sample within 10 min, with a droplet diameter of around 110 µm and a coefficient of variation (CV) value of 0.82%. Staphylococcus aureus was quantified via the proposed platform. The results demonstrated a highly accurate correlation coefficient (R = 0.9998), and the detection limit reached a concentration of 1.7 × 102 copies/µL. The entire process of the droplet digital LAMP reaction, from droplet generation to incubation to quantitative results, took a maximum of 70 min.
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Técnicas de Amplificação de Ácido Nucleico , Staphylococcus aureus , Fluorescência , Dispositivos Lab-On-A-Chip , Limite de Detecção , Técnicas Analíticas Microfluídicas , Técnicas de Diagnóstico MolecularRESUMO
The co-infection of dengue and COVID-19 has been regarded as a public health issue for dengue-endemic countries during the COVID-19 pandemic. Travel restrictions might decrease the chance of mosquitoes biting and, thus, reduce the risk of dengue transmission. However, the spread of dengue was reported to increase with the policies of lockdowns and social distancing in specific areas due to delayed interventions in dengue transmission. Of cases experiencing dengue and COVID-19 co-infection, most recovered after receiving supportive care and/or steroid therapy. However, some episodes of severe or fatal diseases in specific individuals, such as pregnant women, have been reported, and the clinical course of this co-infection is unrecognized or unpredictable. Accordingly, it is crucial to promptly identify predictors of developing severe viral diseases among co-infection patients.
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CONTEXT: Patients with Cushing's syndrome (CS) have higher risk of obesity and diabetes, which are important risk factors of cancers. However, if patients with CS have a higher incidence of cancer remains unknown. OBJECTIVE: To investigate if endogenous CS is associated with increased cancer incidence. DESIGN: A nationwide cohort study. SETTING: Analysis of the data retrieved from Taiwan's National Health Insurance program in 2006-2017. PARTICIPANTS: Between 2006-2017, 1278 patients with newly diagnosed endogenous CS were identified. Among them, 1246 patients without a history of malignancy were enrolled in this study. EXPOSURES: Endogenous CS. MAIN OUTCOMES MEASURES: The age- and sex-standardized incidence rate of all-cause cancer and age-sex-calendar year standardized incidence ratio (SIR) of cancer in association with endogenous CS. RESULTS: The age- and sex-standardized incidences of CS decreased from 4.84 to 3.77 per million person-years between 2006-2017. The age at diagnosis of CS was 45.3 ± 14.8 years, and 80.0% of the patients were female. Cushing's disease and adrenal CS accounted for 35.4% and 64.6% of patients with CS, respectively. The incidence rate of cancer in patients with CS was 7.77 (95% Confidence Interval [CI] = 5.84-10.14) per 1000 person-years, with an SIR of 2.08 (95% CI = 1.54-2.75). The three most common cancer types were liver (27.7%), kidney (16.7%), and lung (13.0%). CONCLUSIONS: Patients with endogenous CS have a higher incidence of cancer.
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Background: Serum D-dimer level has been associated with worsening outcomes in patients with acute myocardial infarction. This study aimed to explore the association between serum D-dimer level and clinical outcomes in Taiwanese patients with acute myocardial infarction. Methods: We analyzed Tri-Service General Hospital-Coronary Heart Disease registry data related to patients with acute myocardial infarction who were admitted between January 2014 and December 2018. A total of 748 patients were enrolled and categorized into high (≥ 495 ng/ml) and low (< 495 ng/ml) D-dimer groups. The primary endpoint was in-hospital mortality, and secondary endpoints were post-discharge mortality and post-discharge major adverse cardiovascular events. Results: Overall, 139 patients died, with 77 from cardiovascular causes and 62 from non-cardiovascular causes. In-hospital mortality was higher in the high D-dimer group than in the low D-dimer group. Among the patients alive at discharge, those with a high D-dimer level had higher cardiovascular mortality and future major adverse cardiovascular events than those with a low D-dimer level. Multivariate Cox regression analysis revealed that higher serum D-dimer levels were significantly associated with higher risks of in-hospital mortality [hazard ratio (HR) = 1.11; 95% confidence interval (CI), 1.06-1.16, p < 0.001], subsequent cardiovascular mortality after discharge (HR = 1.15; 95% CI, 1.08-1.22, p < 0.001), and major adverse cardiovascular events (HR = 1.10; 95% CI, 1.04-1.16, p < 0.001). Conclusions: This is the first study in Taiwan to demonstrate that a higher baseline serum D-dimer level was independently associated with higher risks of in-hospital mortality, post-discharge mortality, and major adverse cardiovascular events in patients with acute myocardial infarction.
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BACKGROUND: Bacteraemia is a critical condition that generally leads to substantial morbidity and mortality. It is unclear whether delayed antimicrobial therapy (and/or source control) has a prognostic or defervescence effect on patients with source-control-required (ScR) or unrequired (ScU) bacteraemia. METHODS: The multicenter cohort included treatment-naïve adults with bacteraemia in the emergency department. Clinical information was retrospectively obtained and etiologic pathogens were prospectively restored to accurately determine the time-to-appropriate antibiotic (TtAa). The association between TtAa or time-to-source control (TtSc, for ScR bacteraemia) and 30-day crude mortality or delayed defervescence were respectively studied by adjusting independent determinants of mortality or delayed defervescence, recognised by a logistic regression model. RESULTS: Of the total 5477 patients, each hour of TtAa delay was associated with an average increase of 0.2% (adjusted odds ratio [AOR], 1.002; P < 0.001) and 0.3% (AOR 1.003; P < 0.001) in mortality rates for patients having ScU (3953 patients) and ScR (1524) bacteraemia, respectively. Notably, these AORs were augmented to 0.4% and 0.5% for critically ill individuals. For patients experiencing ScR bacteraemia, each hour of TtSc delay was significantly associated with an average increase of 0.31% and 0.33% in mortality rates for overall and critically ill individuals, respectively. For febrile patients, each additional hour of TtAa was significantly associated with an average 0.2% and 0.3% increase in the proportion of delayed defervescence for ScU (3085 patients) and ScR (1266) bacteraemia, respectively, and 0.5% and 0.9% for critically ill individuals. For 1266 febrile patients with ScR bacteraemia, each hour of TtSc delay respectively was significantly associated with an average increase of 0.3% and 0.4% in mortality rates for the overall population and those with critical illness. CONCLUSIONS: Regardless of the need for source control in cases of bacteraemia, there seems to be a significant association between the prompt administration of appropriate antimicrobials and both a favourable prognosis and rapid defervescence, particularly among critically ill patients. For ScR bacteraemia, delayed source control has been identified as a determinant of unfavourable prognosis and delayed defervescence. Moreover, this association with patient survival and the speed of defervescence appears to be augmented among critically ill patients.
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Bacteriemia , Serviço Hospitalar de Emergência , Humanos , Bacteriemia/tratamento farmacológico , Bacteriemia/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Serviço Hospitalar de Emergência/organização & administração , Serviço Hospitalar de Emergência/estatística & dados numéricos , Idoso , Estudos Retrospectivos , Adulto , Antibacterianos/uso terapêutico , Fatores de Tempo , Estudos de Coortes , Anti-Infecciosos/uso terapêutico , Tempo para o Tratamento/estatística & dados numéricos , Tempo para o Tratamento/normasRESUMO
Angiopoietin-like protein 4 (ANGPTL4) is a secretory glycoprotein involved in regulating glucose homeostasis in non-pregnant subjects. However, its role in glucose metabolism during pregnancy and the pathophysiology of gestational diabetes mellitus (GDM) remains elusive. Thus, this study aimed to clarify the relationship between ANGPTL4 and GDM and investigate the pathophysiology of placental ANGPTL4 in glucose metabolism. We investigated this issue using blood and placenta samples in 957 pregnant women, the human 3A-sub-E trophoblast cell line, and the L6 skeletal muscle cell line. We found that ANGPTL4 expression in the placenta was higher in obese pregnant women than in lean controls. Palmitic acid significantly induced ANGPTL4 expression in trophoblast cells in a dose-response manner. ANGPTL4 overexpression in trophoblast cells resulted in endoplasmic reticulum (ER) stress, which stimulated the expression and secretion of growth hormone-variant (GH2) but not human placental lactogen. In L6 skeletal muscle cells, soluble ANGPTL4 suppressed insulin-mediated glucose uptake through the epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinases 1/2 (ERK 1/2) pathways. In pregnant women, plasma ANGPTL4 concentrations in the first trimester predicted the incidence of GDM and were positively associated with BMI, plasma triglyceride, and plasma GH2 in the first trimester. However, they were negatively associated with insulin sensitivity index ISI0,120 in the second trimester. Overall, placental ANGPTL4 is induced by obesity and is involved in the pathophysiology of GDM via the induction of ER stress and GH2 secretion. Soluble ANGPTL4 can lead to insulin resistance in skeletal muscle cells and is an early biomarker for predicting GDM.
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BACKGROUND: Male hypogonadism is not uncommon in people with HIV (PWH), with estimated prevalence ranging from 9% to 16%. Existing data are limited on the serum testosterone levels in PWH in Asian populations. METHODS: We enrolled HIV-positive men who have sex with men (MSM) and had been on stable antiretroviral therapy and MSM without HIV between February 2021 and November 2022. Serum free testosterone levels, sex hormone-binding globulins and other associated hormones were measured. Multiple linear regression analysis was performed to assess the association between serum free testosterone levels and clinical variables collected. RESULTS: A total of 447 MSM with HIV and 124 MSM without HIV were enrolled. Compared with MSM without HIV, MSM with HIV had a higher age (median, 41 versus 29.5 years) and prevalence of symptomatic hypogonadism (8.3% versus 1.6%). Among MSM who were aged <35 years, there were no significant differences in the serum free testosterone levels and prevalences of hypogonadism between the two groups. In multiple linear regression analysis, serum free testosterone level significantly decreased with advanced age (a decrease of 1.14 pg/mL per 1-year increase) and a higher body-mass index (BMI) (a decrease of 1.07 pg/mL per 1-kg/m2 increase), but was not associated with HIV serostatus. CONCLUSION: We found that MSM with HIV had a higher prevalence of symptomatic hypogonadism than MSM without HIV in Taiwan, which could be attributed to age difference. Serum free testosterone levels were negatively correlated with age and BMI, but did not show a significant correlation with HIV serostatus.
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BACKGROUND: High levels of neutrophil extracellular trap (NET) formation or NETosis and autoantibodies are related to poor prognosis and disease severity of COVID-19 patients. Human angiotensin-converting enzyme 2 (ACE2) cross-reactive anti-severe acute respiratory syndrome coronavirus 2 spike protein receptor-binding domain (SARS-CoV-2 RBD) antibodies (CR Abs) have been reported as one of the sources of anti-ACE2 autoantibodies. However, the pathological implications of CR Abs in NET formation remain unknown. METHODS: In this study, we first assessed the presence of CR Abs in the sera of COVID-19 patients with different severity by serological analysis. Sera and purified IgG from CR Abs positive COVID-19 patients as well as a mouse monoclonal Ab (mAb 127) that can recognize both ACE2 and the RBD were tested for their influence on NETosis and the possible mechanisms involved were studied. RESULTS: An association between CR Abs levels and the severity of COVID-19 in 120 patients was found. The CR Abs-positive sera and IgG from severe COVID-19 patients and mAb 127 significantly activated human leukocytes and triggered NETosis, in the presence of RBD. This NETosis, triggered by the coexistence of CR Abs and RBD, activated thrombus-related cells but was abolished when the interaction between CR Abs and ACE2 or Fc receptors was disrupted. We also revealed that CR Abs-induced NETosis was suppressed in the presence of recombinant ACE2 or the Src family kinase inhibitor, dasatinib. Furthermore, we found that COVID-19 vaccination not only reduced COVID-19 severity but also prevented the production of CR Abs after SARS-CoV-2 infection. CONCLUSIONS: Our findings provide possible pathogenic effects of CR Abs in exacerbating COVID-19 by enhancing NETosis, highlighting ACE2 and dasatinib as potential treatments, and supporting the benefit of vaccination in reducing disease severity and CR Abs production in COVID-19 patients.
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COVID-19 , Humanos , Animais , Camundongos , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2 , Vacinas contra COVID-19 , Dasatinibe , Imunoglobulina G/metabolismo , Autoanticorpos/metabolismo , Glicoproteína da Espícula de Coronavírus , Ligação ProteicaRESUMO
Dietary habits have been proven to have an impact on the microbial composition and health of the human gut. Over the past decade, researchers have discovered that gut microbiota can use nutrients to produce metabolites that have major implications for human physiology. However, there is no comprehensive system that specifically focuses on identifying nutrient deficiencies based on gut microbiota, making it difficult to interpret and compare gut microbiome data in the literature. This study proposes an analytical platform, NURECON, that can predict nutrient deficiency information in individuals by comparing their metagenomic information to a reference baseline. NURECON integrates a next-generation bacterial 16S rRNA analytical pipeline (QIIME2), metabolic pathway prediction tools (PICRUSt2 and KEGG), and a food compound database (FooDB) to enable the identification of missing nutrients and provide personalized dietary suggestions. Metagenomic information from total number of 287 healthy subjects was used to establish baseline microbial composition and metabolic profiles. The uploaded data is analyzed and compared to the baseline for nutrient deficiency assessment. Visualization results include gut microbial composition, related enzymes, pathways, and nutrient abundance. NURECON is a user-friendly online platform that provides nutritional advice to support dietitians' research or menu design.
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Dieta , Microbioma Gastrointestinal , Humanos , RNA Ribossômico 16S/genética , Microbioma Gastrointestinal/genética , Metagenoma , Necessidades NutricionaisRESUMO
Vascular adhesion protein-1 (VAP-1) plays a dual role with its adhesive and enzymatic properties, facilitating leukocyte migration to sites of inflammation and catalyzing the breakdown of primary amines into harmful by-products, which are linked to diabetic complications. Present in various tissues, VAP-1 also circulates in a soluble form in the bloodstream. Diabetes is associated with several complications such as cardiovascular disease, retinopathy, nephropathy, and neuropathy, significantly contributing to disability and mortality. These complications arise from hyperglycemia-induced oxidative stress, inflammation, and the formation of advanced glycation end-products (AGEs). Earlier research, including our own from the 1990s and early 2000s, has underscored the critical role of VAP-1 in these pathological processes, prompting extensive investigation into its contribution to diabetic complications. In this review, we examine the involvement of VAP-1 in diabetes and its complications, alongside its link to other conditions related to diabetes, such as cancer and metabolic dysfunction-associated fatty liver disease. We also explore the utility of soluble VAP-1 as a biomarker for diabetes, its complications, and other related conditions. Since the inhibition of VAP-1 to treat diabetic complications is a novel and promising treatment option, further studies are needed to translate the beneficial effect of VAP-1 inhibitors observed in animal studies to clinical trials recruiting human subjects. Besides, future studies should focus on using serum sVAP-1 levels for risk assessment in diabetic patients, identifying those who need intensive glycemic control, and determining the patient population that would benefit most from VAP-1 inhibitor therapies.
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Amina Oxidase (contendo Cobre) , Moléculas de Adesão Celular , Complicações do Diabetes , Humanos , Amina Oxidase (contendo Cobre)/sangue , Amina Oxidase (contendo Cobre)/metabolismo , Moléculas de Adesão Celular/metabolismo , Complicações do Diabetes/etiologia , Complicações do Diabetes/metabolismo , Animais , Diabetes Mellitus/metabolismo , Biomarcadores , Produtos Finais de Glicação Avançada/metabolismoRESUMO
We present an in-depth analysis of dyslipidemia management strategies for patients with diabetes mellitus in Taiwan. It critically examines the disparity between established guideline recommendations and actual clinical practices, particularly in the context of evolving policies affecting statin prescriptions. The focus is on synthesizing the most recent findings concerning lipid management in patients with diabetes mellitus, with a special emphasis on establishing consensus regarding low-density lipoprotein cholesterol treatment targets. The article culminates in providing comprehensive, evidence-based recommendations tailored to the unique needs of those living with diabetes mellitus in Taiwan. It underscores the criticality of personalized care approaches, which incorporate multifaceted factors, and the integration of novel therapeutic options to enhance cardiovascular health outcomes.
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Consenso , Dislipidemias , Humanos , Taiwan/epidemiologia , Dislipidemias/tratamento farmacológico , Dislipidemias/terapia , Diabetes Mellitus/terapia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Guias de Prática Clínica como Assunto/normas , LDL-Colesterol/sangueRESUMO
A detection and classification machine-learning model to inspect Thin Film Transistor Liquid Crystal Display (TFT-LCD) Mura is proposed in this study. To improve the capability of the machine-learning model to inspect panels' low-contrast grayscale images, piecewise gamma correction and a Selective Search algorithm are applied to detect and optimize the feature regions based on the Semiconductor Equipment and Materials International Mura (SEMU) specifications. In this process, matching the segment proportions to gamma values of piecewise gamma is a task that involves derivative-free optimization which is trained by adaptive particle swarm optimization. The detection accuracy rate (DAR) is approximately 93.75%. An enhanced convolutional neural network model is then applied to classify the Mura type through using the Taguchi experimental design method that identifies the optimal combination of the convolution kernel and the maximum pooling kernel sizes. A remarkable defect classification accuracy rate (CAR) of approximately 96.67% is ultimately achieved. The entire defect detection and classification process can be completed in about 3 milliseconds.
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Maximal exercise capacity is reduced at altitude or during hypoxia at sea level. It has been suggested that this might reflect increased right ventricular afterload due to hypoxic pulmonary vasoconstriction. We have shown previously that the pulmonary vascular sensitivity to hypoxia is enhanced by sustained isocapnic hypoxia, and inhibited by intravenous iron. In this study, we tested the hypothesis that elevated pulmonary artery pressure contributes to exercise limitation during acute hypoxia. Twelve healthy volunteers performed incremental exercise tests to exhaustion breathing 12% oxygen, before and after sustained (8-h) isocapnic hypoxia at sea level. Intravenous iron sucrose (n = 6) or saline placebo (n = 6) was administered immediately before the sustained hypoxia. In the placebo group, there was a substantial (12.6 ± 1.5 mmHg) rise in systolic pulmonary artery pressure (SPAP) during sustained hypoxia, but no associated fall in maximal exercise capacity breathing 12% oxygen. In the iron group, the rise in SPAP during sustained hypoxia was markedly reduced (3.4 ± 1.0 mmHg). There was a small rise in maximal exercise capacity following sustained hypoxia within the iron group, but no overall effect of iron, compared with saline. These results do not support the hypothesis that elevated SPAP inhibits maximal exercise capacity during acute hypoxia in healthy volunteers.
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Oxigênio , Vasoconstrição , Humanos , Tolerância ao Exercício , Voluntários Saudáveis , Artéria Pulmonar , Hipóxia , Altitude , Ferro/uso terapêuticoAssuntos
Doenças Cardiovasculares , Comportamento de Redução do Risco , Humanos , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/etiologia , Obesidade/complicações , Diabetes Mellitus/prevenção & controle , Diabetes Mellitus/terapia , Diabetes Mellitus Tipo 2/prevenção & controle , Redução de PesoRESUMO
Clostridioides difficile is a Gram-positive, anaerobic, and spore-forming bacterial member of the human gut microbiome. The primary virulence factors of C. difficile are toxin A and toxin B. These toxins damage the cell cytoskeleton and cause various diseases, from diarrhea to severe pseudomembranous colitis. Evidence suggests that bacteriophages can regulate the expression of the pathogenicity locus (PaLoc) genes of C. difficile. We previously demonstrated that the genome of the C. difficile RT027 strain NCKUH-21 contains a prophage-like DNA sequence, which was found to be markedly similar to that of the φCD38-2 phage. In the present study, we investigated the mechanisms underlying the φNCKUH-21-mediated regulation of the pathogenicity and the PaLoc genes expression in the lysogenized C. difficile strain R20291. The carriage of φNCKUH-21 in R20291 cells substantially enhanced toxin production, bacterial motility, biofilm formation, and spore germination in vitro. Subsequent mouse studies revealed that the lysogenized R20291 strain caused a more severe infection than the wild-type strain. We screened three φNCKUH-21 genes encoding DNA-binding proteins to check their effects on PaLoc genes expression. The overexpression of NCKUH-21_03890, annotated as a transcriptional regulator (phage transcriptional regulator X, PtrX), considerably enhanced toxin production, biofilm formation, and bacterial motility of R20291. Transcriptome analysis further confirmed that the overexpression of ptrX led to the upregulation of the expression of toxin genes, flagellar genes, and csrA. In the ptrX-overexpressing R20291 strain, PtrX influenced the expression of flagellar genes and the sigma factor gene sigD, possibly through an increased flagellar phase ON configuration ratio.
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Toxinas Bacterianas , Bacteriófagos , Clostridioides difficile , Humanos , Animais , Camundongos , Toxinas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Clostridioides difficile/metabolismo , Virulência , Bacteriófagos/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão GênicaRESUMO
BACKGROUND: The residual risks of atherosclerotic cardiovascular disease in statin-treated patients with diabetes remain unclear. This study was conducted to identify factors associated with these residual risks in patients with no prior vascular event. METHODS: Data on 683 statin-using patients with type 2 diabetes mellitus (T2DM) from the Taiwan Diabetes Registry were used in this study. Patients aged < 25 or > 65 years at the time of diabetes diagnosis and those with diabetes durations ≥ 20 years were excluded. The United Kingdom Prospective Diabetes Study risk engine (version 2.01; https://www.dtu.ox.ac.uk/riskengine/ ) was used to calculate 10-year residual nonfatal and fatal coronary heart disease (CHD) and stroke risks. Associations of these risks with physical and biochemical variables, including medication use and comorbidity, were examined. RESULTS: The 10-year risks of nonfatal CHD in oral anti-diabetic drug (OAD), insulin and OAD plus insulin groups were 11.8%, 16.0%, and 16.8%, respectively. The 10-year risks of nonfatal stroke in OAD, insulin and OAD plus insulin groups were 3.0%, 3.4%, and 4.3%, respectively. In the multivariate model, chronic kidney disease (CKD), neuropathy, insulin use, calcium-channel blocker (CCB) use, higher body mass indices (BMI), low-density lipoprotein (LDL), fasting glucose, log-triglyceride (TG), and log-alanine transaminase (ALT) levels were associated with an increased CHD risk. The residual risk of stroke was associated with CKD, neuropathy, CCB use, and lower LDL cholesterol levels, higher BMI and diastolic blood pressure. CONCLUSION: This study indicated that insulin was probably a residual risk factor of CHD but not stroke, and that there was a possible presence of obesity paradox in patients with T2DM on statin therapy. In addition to lowering TG and normalizing fasting glucose levels, lower LDL cholesterol level is better for reduction of risk of CHD on statin therapy. On the other hand, lower LDL cholesterol level could potentially be related to higher risk of stroke among populations receiving statin therapy. These findings suggest potential therapeutic targets for residual cardiovascular risk reduction in patients with T2DM on statin therapy.