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The susceptibility, risk factors, and prognosis of COVID-19 in patients with inflammatory bowel disease (IBD) remain unknown. Thus, our study aims to assess the prevalence and clinical outcomes of COVID-19 in IBD. We searched PubMed, EMBASE, and medRxiv from 2019 to 1 June 2022 for cohort and case-control studies comparing the prevalence and clinical outcomes of COVID-19 in patients with IBD and in the general population. We also compared the outcomes of patients receiving and not receiving 5-aminosalicylates (ASA), tumour necrosis factor antagonists, biologics, systemic corticosteroids, or immunomodulators for IBD. Thirty five studies were eligible for our analysis. Pooled odds ratio of COVID-19-related hospitalisation, intensive care unit (ICU) admission, or death in IBD compared to in non-IBD were 0.58 (95% confidence interval (CI) = 0.28-1.18), 1.09 (95% CI = 0.27-4.47), and 0.67 (95% CI = 0.32-1.42), respectively. Inflammatory bowel disease was not associated with increased hospitalisation, ICU admission, or death. Susceptibility to COVID-19 did not increase with any drugs for IBD. Hospitalisation, ICU admission, and death were more likely with 5-ASA and corticosteroid use. COVID-19-related hospitalisation (Odds Ratio (OR): 0.53; 95% CI = 0.38-0.74) and death (OR: 0.13; 95% CI = 0.13-0.70) were less likely with Crohn's disease than ulcerative colitis (UC). In conclusion, IBD does not increase the mortality and morbidity of COVID-19. However, physicians should be aware that additional monitoring is needed in UC patients or in patients taking 5-ASA or systemic corticosteroids.
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COVID-19 , Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Humanos , Enfermedades Inflamatorias del Intestino/inducido químicamente , Enfermedades Inflamatorias del Intestino/patología , Colitis Ulcerosa/inducido químicamente , Enfermedad de Crohn/inducido químicamente , Corticoesteroides , MesalaminaRESUMEN
SIGNIFICANCE STATEMENT: The kidney failure risk equation (KFRE) uses age, sex, GFR, and urine albumin-to-creatinine ratio (ACR) to predict 2- and 5-year risk of kidney failure in populations with eGFR <60 ml/min per 1.73 m 2 . However, the CKD-EPI 2021 creatinine equation for eGFR is now recommended for use but has not been fully tested in the context of KFRE. In 59 cohorts comprising 312,424 patients with CKD, the authors assessed the predictive performance and calibration associated with the use of the CKD-EPI 2021 equation and whether additional variables and accounting for the competing risk of death improves the KFRE's performance. The KFRE generally performed well using the CKD-EPI 2021 eGFR in populations with eGFR <45 ml/min per 1.73 m 2 and was not improved by adding the 2-year prior eGFR slope and cardiovascular comorbidities. BACKGROUND: The kidney failure risk equation (KFRE) uses age, sex, GFR, and urine albumin-to-creatinine ratio (ACR) to predict kidney failure risk in people with GFR <60 ml/min per 1.73 m 2 . METHODS: Using 59 cohorts with 312,424 patients with CKD, we tested several modifications to the KFRE for their potential to improve the KFRE: using the CKD-EPI 2021 creatinine equation for eGFR, substituting 1-year average ACR for single-measure ACR and 1-year average eGFR in participants with high eGFR variability, and adding 2-year prior eGFR slope and cardiovascular comorbidities. We also assessed calibration of the KFRE in subgroups of eGFR and age before and after accounting for the competing risk of death. RESULTS: The KFRE remained accurate and well calibrated overall using the CKD-EPI 2021 eGFR equation. The other modifications did not improve KFRE performance. In subgroups of eGFR 45-59 ml/min per 1.73 m 2 and in older adults using the 5-year time horizon, the KFRE demonstrated systematic underprediction and overprediction, respectively. We developed and tested a new model with a spline term in eGFR and incorporating the competing risk of mortality, resulting in more accurate calibration in those specific subgroups but not overall. CONCLUSIONS: The original KFRE is generally accurate for eGFR <45 ml/min per 1.73 m 2 when using the CKD-EPI 2021 equation. Incorporating competing risk methodology and splines for eGFR may improve calibration in low-risk settings with longer time horizons. Including historical averages, eGFR slopes, or a competing risk design did not meaningfully alter KFRE performance in most circumstances.
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Insuficiencia Renal Crónica , Insuficiencia Renal , Humanos , Anciano , Creatinina , Factores de Transcripción , AlbúminasRESUMEN
OBJECTIVE: This study examined the effect of cognitive bias modification for interpretation (CBM-I) training in Korean women with eating disorders (EDs). METHOD: Sixty-three women with EDs participated in the study. Participants were randomly assigned to the intervention group where they received six sessions of CBM-I training (n = 31) in addition to treatment-as-usual or were put on a waiting list (n = 32). Participants' interpretation and attention biases, emotion regulation, affect, and ED psychopathology were assessed at baseline, end-of-intervention (4 weeks), and follow-up (8 weeks). RESULTS: Participants who completed the CBM-I training displayed greater reductions in negative interpretation bias (Δη2 = 0.107) and emotion dysregulation (Δη2 = 0.085) with medium to large effect sizes compared to the control group, which were maintained from baseline to follow-up. Disengagement from negative faces and a focus on positive faces was found in the intervention group with a moderate effect size at the end-of-intervention (Δη2 = 0.090). Both intervention and control groups showed improvements in ED psychopathology. Baseline neuroticism was positively correlated with CBM-I effect. DISCUSSION: The results suggest that modifying interpretation bias towards ambiguous social stimuli might be an effective adjuvant treatment to reduce negative expectations of social situations and improve emotion regulation in women with bulimia nervosa and anorexia nervosa.
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Terapia Cognitivo-Conductual , Trastornos de Alimentación y de la Ingestión de Alimentos , Humanos , Femenino , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Trastornos de Alimentación y de la Ingestión de Alimentos/terapia , Adulto , Terapia Cognitivo-Conductual/métodos , Distancia Psicológica , Adulto Joven , Sesgo Atencional , Regulación Emocional , República de Corea , Resultado del TratamientoRESUMEN
Patients with end stage kidney disease (ESKD) and a previous acute myocardial infarction (AMI) have less access to KT. Data on ESKD patients with an AMI history who underwent first KT or dialysis between January 2007 and December 2018 were extracted from the Korean National Health Insurance Service. Patients who underwent KT (n = 423) were chronologically matched in a 1:3 ratio with those maintained on dialysis (n = 1,269) at the corresponding dates, based on time-conditional propensity scores. The 1, 5, and 10 years cumulative incidences for all-cause mortality were 12.6%, 39.1%, and 60.1% in the dialysis group and 3.1%, 7.2%, and 14.5% in the KT group. Adjusted hazard ratios (HRs) of KT versus dialysis were 0.17 (95% confidence interval [CI], 0.12-0.24; p < 0.001) for mortality and 0.38 (95% CI, 0.23-0.51; p < 0.001) for major adverse cardiovascular events (MACE). Of the MACE components, KT was most protective against cardiovascular death (HR, 0.23; 95% CI, 0.12-0.42; p < 0.001). Protective effects of KT for all-cause mortality and MACE were consistent across various subgroups, including patients at higher risk (e.g., age >65 years, recent AMI [<6 months], congestive heart failure). KT is associated with lower all-cause mortality and MACE than maintenance dialysis patients with a prior AMI.
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Insuficiencia Cardíaca , Fallo Renal Crónico , Trasplante de Riñón , Infarto del Miocardio , Humanos , Anciano , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/cirugía , Infarto del Miocardio/cirugía , Diálisis RenalRESUMEN
OBJECTIVE: Heightened sensitivity toward social rejection has been implicated in eating disorders (ED) and personality disorder (PD). This study examined the effect of a cognitive bias modification training (CBM-I) targeting the interpretation of ambiguous social situations in individuals with comorbid ED and PD. METHOD: A total of 128 participants [33 with ED and PD, 22 with ED-only, 22 with PD-only, and 51 healthy controls (HC)] were recruited from a hospital and university settings, and included in the final analyses. The participants were randomly assigned to a CBM-I task with benign resolutions or a control task with neutral resolutions in a counterbalanced order in two sessions using a within-subject design. Interpretation bias toward social stimuli was measured using the ambiguous sentence completion task before and after completing the assigned task. RESULTS: The CBM-I task increased benign and decreased negative interpretations with large effect sizes in the diagnostic groups, and with a moderate effect size in the HC group. Participants' anxiety levels were also reduced after the task. The size of the change in negative interpretation was positively associated with baseline negative affect, and negatively associated with baseline positive affect. DISCUSSION: The results suggest that modifying interpretation bias has the potential as a transdiagnostic target of treatment for ED and PD, and a fully powered clinical trial with consecutive sessions would be warranted. PUBLIC SIGNIFICANCE: Participants with eating disorders and/or personality disorder, and healthy controls completed a single session of a cognitive training intervention targeting rejection sensitivity. The training produced a large decrease in negative interpretation in the diagnostic groups, and a moderate effect in healthy controls. The findings indicate that training for positive processing of social information may be of value to augment treatment in conditions such as eating disorders and personality disorder, in which there are high levels of rejection sensitivity.
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Terapia Cognitivo-Conductual , Trastornos de Alimentación y de la Ingestión de Alimentos , Humanos , Terapia Cognitivo-Conductual/métodos , Trastornos de Alimentación y de la Ingestión de Alimentos/terapia , Sesgo , HospitalesRESUMEN
BACKGROUND: This study aimed to analyze low-density lipoprotein cholesterol (LDL-C) levels and their relationship with mortality in order to identify the appropriate lipid profile for older Korean hemodialysis patients. METHODS: We enrolled a total of 2,732 incident hemodialysis patients aged > 70 years from a retrospective cohort of the Korean Society of Geriatric Nephrology from 2010 Jan to 2017 Dec, which included 17 academic hospitals in South Korea. Of these patients, 1,709 were statin-naïve, and 1,014 were analyzed after excluding those with missing LDL-C level data. We used multivariate Cox regression analysis to select risk factors from 20 clinical variables among the LDL-C groups. RESULTS: The mean age of the entire patient population was 78 years, with no significant differences in age between quartiles Q1 to Q4. However, the proportion of males decreased as the quartiles progressed towards Q4 (p < 0.001). The multivariate Cox regression analysis, which included all participants, showed that low LDL-C levels were associated with all-cause mortality. In the final model, compared to Q1, the hazard ratios (95% confidence interval) were 0.77 (0.620-0.972; p = 0.027), 0.85 (0.676-1.069; p = 0.166), and 0.65 (0.519-0.824; p < 0.001) for Q2, Q3, and Q4, respectively, after adjusting for covariates, such as conventional and age-specific risk factors. The final model demonstrated that all-cause mortality increased as LDL-C levels decreased, as confirmed by a restrictive cubic spline plot. CONCLUSIONS: In older hemodialysis patients who had not previously received dyslipidemia treatment, elevated LDL-C levels were not associated with increased all-cause mortality. Intriguingly, lower LDL-C levels appear to be associated with an unfavorable effect on all-cause mortality among high-risk hemodialysis patients.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas , Masculino , Humanos , Anciano , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , LDL-Colesterol , Estudios Retrospectivos , Diálisis Renal , Factores de RiesgoRESUMEN
Sarcopenia is the age-related loss of muscle mass and function and no pharmacological medication has been approved for its treatment. We established an atrogin-1/MAFbx promoter assay to find drug candidates that inhibit myotube atrophy. Alverine citrate (AC) was identified using high-throughput screening of an existing drug library. AC is an established medicine for stomach and intestinal spasms. AC treatment increased myotube diameter and inhibited atrophy signals induced by either C26-conditioned medium or dexamethasone in cultured C2C12 myoblasts. AC also enhanced myoblast fusion through the upregulation of fusion-related genes during C2C12 myoblast differentiation. Oral administration of AC improves muscle mass and physical performance in aged mice, as well as hindlimb-disused mice. Taken together, our data suggest that AC may be a novel therapeutic candidate for improving muscle weakness, including sarcopenia.
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Envejecimiento/genética , Diferenciación Celular/efectos de los fármacos , Atrofia Muscular/prevención & control , Parasimpatolíticos/farmacología , Propilaminas/farmacología , Sarcopenia/prevención & control , Envejecimiento/metabolismo , Animales , Biomarcadores/metabolismo , Cadherinas/genética , Cadherinas/metabolismo , Caveolina 3/genética , Caveolina 3/metabolismo , Línea Celular , Dexametasona/farmacología , Modelos Animales de Enfermedad , Expresión Génica , Ensayos Analíticos de Alto Rendimiento , Inmovilización , Integrina beta1/genética , Integrina beta1/metabolismo , Ratones , Ratones Endogámicos C57BL , Desarrollo de Músculos/genética , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patología , Fuerza Muscular/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Atrofia Muscular/genética , Atrofia Muscular/metabolismo , Atrofia Muscular/patología , Mioblastos/efectos de los fármacos , Mioblastos/metabolismo , Mioblastos/patología , Sarcopenia/genética , Sarcopenia/metabolismo , Sarcopenia/patologíaRESUMEN
The aim of this study is to provide a more accurate representation of COVID-19's case fatality rate (CFR) by performing meta-analyses by continents and income, and by comparing the result with pooled estimates. We used multiple worldwide data sources on COVID-19 for every country reporting COVID-19 cases. On the basis of data, we performed random and fixed meta-analyses for CFR of COVID-19 by continents and income according to each individual calendar date. CFR was estimated based on the different geographical regions and levels of income using three models: pooled estimates, fixed- and random-model. In Asia, all three types of CFR initially remained approximately between 2.0% and 3.0%. In the case of pooled estimates and the fixed model results, CFR increased to 4.0%, by then gradually decreasing, while in the case of random-model, CFR remained under 2.0%. Similarly, in Europe, initially, the two types of CFR peaked at 9.0% and 10.0%, respectively. The random-model results showed an increase near 5.0%. In high-income countries, pooled estimates and fixed-model showed gradually increasing trends with a final pooled estimates and random-model reached about 8.0% and 4.0%, respectively. In middle-income, the pooled estimates and fixed-model have gradually increased reaching up to 4.5%. in low-income countries, CFRs remained similar between 1.5% and 3.0%. Our study emphasizes that COVID-19 CFR is not a fixed or static value. Rather, it is a dynamic estimate that changes with time, population, socioeconomic factors, and the mitigatory efforts of individual countries.
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COVID-19 , Asia , COVID-19/epidemiología , Europa (Continente)/epidemiología , Humanos , SARS-CoV-2 , Factores SocioeconómicosRESUMEN
Various melatonin supplementations have been developed to improve health outcomes in various clinical conditions. Thus, we sought to evaluate and summarize the effect of melatonin treatments in clinical settings for health outcomes. We searched PubMed/Medline, Embase, and Cochrane Library from inception to 4 February 2021. We included meta-analyses of randomized controlled trials investigating the melatonin intervention for any health outcome. Based on the different effect sizes of each meta-analysis, we calculated random models' standardized mean differences or risk ratios. We observed robust evidence supported by statistical significance with non-considerable heterogeneity between studies for sleep-related problems, cancer, surgical patients, and pregnant women. Patients with sleep disorder, sleep onset latency (SMD 0.33, 95% CI: 0.10 - 0.56, P < 0.01) were significantly improved whereas no clear evidence was shown with sleep efficiency (1.10, 95% CI: -0.26 to 2.45). The first analgesic requirement time (SMD 5.81, 95% CI: 2.57-9.05, P < 0.001) of surgical patients was distinctly improved. Female patients under artificial reproductive technologies had significant increase in the top-quality embryos (SMD 0.53, 95% CI: 0.27 - 0.79, P < 0.001), but no statistically clear evidence was found in the live birth rate (SMD 1.20, 95% CI: 0.83 - 1.72). Survival at one year (RR 1.90, 95% CI: 1.28 - 2.83, P < 0.005) significantly increased with cancer patients. Research on melatonin interventions to treat clinical symptoms and sleep problems among diverse health conditions was identified and provided considerable evidence. Future well-designed randomized clinical trials of high quality and subgroup quantitative analyses are essential.
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Melatonina/uso terapéutico , Humanos , Trastornos Mentales/tratamiento farmacológico , Enfermedades Metabólicas/tratamiento farmacológico , Dolor Postoperatorio/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Trastornos del Sueño-Vigilia/tratamiento farmacológicoRESUMEN
BACKGROUND: Physical activity (PA) is an important risk factor associated with health outcomes. However, the relationship between PA and kidney function decline in older adults remains unclear. We examined the influence of PA on kidney function decline and mortality in community-dwelling older adults. METHODS: Adults aged ≥ 65 years with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 who had available health checkup data from 2009 to 2010 were included. The cohort was followed annually through December 2015 for anthropometric, sociodemographic, and medical information including outcomes and biennially for laboratory information from the health checkup. We divided these patients into three groups according to self-reported PA (Inactive group: no leisure-time PA, Active group: vigorous activity for at least 80 min/week or a sum of moderate-intensity activity and walking for at least 300 min/week, Low-active group: level of PA between the definitions of the other two groups). Associations between the intensity of PA and death, cardiovascular death, and ≥ 50% eGFR decline were investigated. RESULTS: Among 102,353 subjects, 32,984 (32.23%), 54,267 (53.02%), and 15,102 (14.75%) were classified into the inactive, low-active, and active groups, respectively. The active group was younger, contained a higher proportion of men, and had higher frequencies of hypertension, diabetes mellitus, drinking, and smoking than the other groups. The active group had significantly lower incidence rates of mortality, cardiovascular mortality, and kidney function decline than the other groups (all p < 0.001). The active group also showed lower all-cause (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.70-0.82) and cardiovascular mortality (HR, 0.64; 95% CI, 0.53-0.78) and protection against ≥ 50% eGFR decline (HR, 0.81; 95% CI, 0.68-0.97) compared with the inactive group in the fully adjusted Cox proportional hazards regression model. CONCLUSIONS: High PA was an independent modifiable lifestyle factor for reducing mortality and protecting against declines in kidney function in older adults.
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Enfermedades Cardiovasculares , Vida Independiente , Masculino , Humanos , Anciano , Estudios de Cohortes , Ejercicio Físico , Factores de Riesgo , Riñón/fisiologíaRESUMEN
Autoimmune diseases are disorders that destruct or disrupt the body's own tissues by its own immune system. Several studies have revealed that polymorphisms of multiple genes are involved in autoimmune diseases. Meanwhile, gene therapy has become a promising approach in autoimmune diseases, and clustered regularly interspaced palindromic repeats and CRISPR-associated protein 9 (CRISPR-Cas9) has become one of the most prominent methods. It has been shown that CRISPR-Cas9 can be applied to knock out proprotein convertase subtilisin/kexin type 9 (PCSK9) or block PCSK9, resulting in lowering low-density lipoprotein cholesterol. In other studies, it can be used to treat rare diseases such as ornithine transcarbamylase (OTC) deficiency and hereditary tyrosinemia. However, few studies on the treatment of autoimmune disease using CRISPR-Cas9 have been reported so far. In this review, we highlight the current and potential use of CRISPR-Cas9 in the management of autoimmune diseases. We summarize the potential target genes for immunomodulation using CRISPR-Cas9 in autoimmune diseases including rheumatoid arthritis (RA), inflammatory bowel diseases (IBD), systemic lupus erythematosus (SLE), multiple sclerosis (MS), type 1 diabetes mellitus (DM), psoriasis, and type 1 coeliac disease. This article will give a new perspective on understanding the use of CRISPR-Cas9 in autoimmune diseases not only through animal models but also in human models. Emerging approaches to investigate the potential target genes for CRISPR-Cas9 treatment may be promising for the tailored immunomodulation of some autoimmune diseases in the near future.
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Enfermedades Autoinmunes/genética , Sistemas CRISPR-Cas/genética , Animales , Edición Génica/métodos , Humanos , ARN Guía de Kinetoplastida/genéticaRESUMEN
It is known that the etiology and clinical outcomes of autoimmune diseases are associated with a combination of genetic and environmental factors. In the case of the genetic factor, the SNPs of the PTPN22 gene have shown strong associations with several diseases. The recent exploding numbers of genetic studies have made it possible to find these associations rapidly, and a variety of autoimmune diseases were found to be associated with PTPN22 polymorphisms. Proteins encoded by PTPN22 play a key role in the adaptative and immune systems by regulating both T and B cells. Gene variants, particularly SNPs, have been shown to significantly disrupt several immune functions. In this review, we summarize the mechanism of how PTPN22 and its genetic variants are involved in the pathophysiology of autoimmune diseases. In addition, we sum up the findings of studies reporting the genetic association of PTPN22 with different types of diseases, including type 1 diabetes mellitus, systemic lupus erythematosus, juvenile idiopathic arthritis, and several other diseases. By understanding these findings comprehensively, we can explain the complex etiology of autoimmunity and help to determine the criteria of disease diagnosis and prognosis, as well as medication developments.
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Enfermedades Autoinmunes , Lupus Eritematoso Sistémico , Proteína Tirosina Fosfatasa no Receptora Tipo 22 , Enfermedades Autoinmunes/genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Sistema Inmunológico/metabolismo , Lupus Eritematoso Sistémico/genética , Polimorfismo de Nucleótido Simple , Proteína Tirosina Fosfatasa no Receptora Tipo 22/genéticaRESUMEN
Shape memory materials have been successfully applied to minimally invasive implantation of medical devices. However, organ-movement-specific shape programing at a microscale level has never been demonstrated despite significant unmet needs. As vein-to-artery grafting induces vein dilation and stenosis, a polymeric self-enclosable external support (SES) is designed to wrap the vascular out-wall. Its micropores are programmed to increase sizes and interconnections upon dilation. Vessel dilation promotes venous maturation, but overdilation induces stenosis by disturbed blood flow. Therefore, the unique elastic shape-fixity of SES provides a foundation to enable a stable microscale shape transition by maintaining the vein dilation. The shape transition of micropore architecture upon dilation induces beneficial inflammation, thereby regenerating vasa vasorum and directing smooth muscle cell migration toward adventitia with the consequent muscle reinforcement of veins. This game-changer approach prevents the stenosis of vein-to-artery grafting by rescuing ischemic disorders and promoting arterial properties of veins.
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Vasa Vasorum , Enfermedades Vasculares , Constricción Patológica , Dilatación , Humanos , Enfermedades Vasculares/prevención & control , VenasRESUMEN
Background and Objectives: Although the need for anticoagulation to prevent thromboembolism is increasing and non-vitamin K antagonist oral anticoagulants (NOACs) have been tried, there is still controversy about the efficacy of anticoagulation in patients with dialysis. Materials and Methods: We retrospectively analyzed the risk and benefit of anticoagulation in dialysis patients with atrial fibrillation (AF). We retrospectively analyzed all data of 89 patients who received dialysis therapy and were diagnosed with AF. Among them, 27 received anticoagulation (11 warfarin and 16 apixaban 2.5 mg twice a day), while 62 received no anticoagulation. Results: In multivariate Cox regression analysis, compared to no anticoagulation treatment, anticoagulation treatment was associated with a low incidence of all-cause mortality (hazard ratios (HR) 0.36; 95% confidence interval (CI) 0.15-0.88). Compared to no anticoagulation treatment, more anticoagulation treatment patients experienced severe bleeding (HR 4.67; 95% CI 1.26-17.25) and any bleeding (HR 2.79; 95% CI 1.01-7.74). Compared to no anticoagulation, warfarin treatment patients were associated with a low incidence of all-cause mortality (HR 0.26; 95% CI 0.09-0.81) and a high incidence of severe bleeding (HR 4.85; 95% CI 1.12-21.10). All-cause mortality and bleeding were not significantly different between no anticoagulation and apixaban treatment patients. Conclusions: In dialysis patients with AF, anticoagulation therapy is associated with an increased incidence of severe bleeding, but anticoagulation therapy is associated with a low incidence of all-cause mortality. Individualized anticoagulation therapy with careful bleeding monitoring is needed in dialysis patients with AF.
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Fibrilación Atrial , Fallo Renal Crónico , Administración Oral , Anticoagulantes/efectos adversos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Humanos , Diálisis Renal , Estudios RetrospectivosRESUMEN
Several protein kinases, including protein kinase C, Ca2+/calmodulin-dependent protein kinase II, and extracellular signal-regulated kinase, play key roles in the regulation of dopamine transporter (DAT) functions. These functions include surface expression, internalization, and forward and reverse transport, with phosphorylation sites for these kinases being linked to distinct regions of the DAT N terminus. Protein phosphatases (PPs) also regulate DAT activity, but the specific residues associated with their activities have not yet been elucidated. In this study, using co-immunoprecipitation followed by MS and immunoblotting analyses, we demonstrate the association of DAT with PP1 and PP2A in the mouse brain and heterologous cell systems. By applying MS in conjunction with a metabolic labeling method, we defined a PP1/2A-sensitive phosphorylation site at Thr-48 in human DAT, a residue that has not been previously reported to be involved in DAT phosphorylation. Site-directed mutagenesis of Thr-48 to Ala (T48A) to prevent phosphorylation enhanced dopamine transport kinetics, supporting a role for this residue in regulating DAT activity. Moreover, T48A-DAT displayed increased palmitoylation, suggesting that phosphorylation/dephosphorylation at this site has an additional regulatory role and reinforcing a previously reported reciprocal relationship between C-terminal palmitoylation and N-terminal phosphorylation.
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Encéfalo/metabolismo , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Dopamina/metabolismo , Proteína Fosfatasa 1/metabolismo , Proteína Fosfatasa 2/metabolismo , Animales , Transporte Biológico Activo/fisiología , Dopamina/genética , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Humanos , Lipoilación/genética , Ratones , Ratones Noqueados , Fosforilación , Proteína Fosfatasa 1/genética , Proteína Fosfatasa 2/genética , Treonina/genética , Treonina/metabolismoRESUMEN
BACKGROUND: South Korea is one of the few countries that has succeeded in flattening the curve of new COVID-19 cases and avoiding a second outbreak by implementing multiple strategies, ranging from an individual level to the population level. OBJECTIVE: We aim to discuss the unique strategies and epidemiological characteristics of COVID-19 in South Korea and present a summary of policies implemented by the Korean government during the COVID-19 pandemic. METHODS: We designed a cross-sectional study of epidemiological data published by the Korea Centers for Disease Control and Prevention on October 1, 2020. We analyzed detailed epidemiological information of COVID-19 cases, including the number of confirmed cases and resulting deaths. RESULTS: As of October 1, 2020, a total of 23,889 confirmed COVID-19 cases and 415 deaths were reported in South Korea. In this paper, we present data on the epidemiological characteristics and transmission of the disease and discuss how the South Korean government, health care providers, and society responded to the COVID-19 outbreak. CONCLUSIONS: Understanding the epidemiological characteristics of COVID-19 in South Korea and the government's successful efforts in managing the spread of the disease can provide important insights to other countries dealing with the ongoing pandemic.
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COVID-19/terapia , Pandemias/estadística & datos numéricos , SARS-CoV-2/patogenicidad , Estudios Transversales , Brotes de Enfermedades , Métodos Epidemiológicos , Humanos , República de Corea/epidemiologíaRESUMEN
Sarcopenia refers to a decrease in skeletal muscle mass and function. Because sarcopenia affects mortality, and causes significant disability, the clinical importance of sarcopenia is emerging. At first, sarcopenia was recognized as an age-related disease but, recently, it has been reported to be prevalent also in younger patients with autoimmune diseases. Specifically, the association of sarcopenia and autoimmune diseases such as rheumatoid arthritis has been studied in detail. Although the pathogenesis of sarcopenia in autoimmune diseases has not been elucidated, chronic inflammation is believed to contribute to sarcopenia, and moreover the pathogenesis seems to be different depending on the respective underlying disease. The definition of sarcopenia differs among studies, which limits direct comparisons. Therefore, in this review, we cover various definitions of sarcopenia used in previous studies and highlight the prevalence of sarcopenia in diverse autoimmune diseases including rheumatoid arthritis, spondyloarthritis, systemic sclerosis, inflammatory bowel disease, and autoimmune diabetes. In addition, we cover the pathogenesis and treatment of sarcopenia in autoimmune and rheumatic diseases. This review provides a comprehensive understanding of sarcopenia in various autoimmune diseases and highlights the need for a consistent definition of sarcopenia.
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Enfermedades Autoinmunes/complicaciones , Enfermedades Reumáticas/complicaciones , Sarcopenia/complicaciones , Humanos , Modelos Biológicos , Sarcopenia/diagnóstico , Sarcopenia/epidemiologíaRESUMEN
Background and objective: Despite medical advances, we are facing the unprecedented disaster of the coronavirus disease 2019 (COVID-19) pandemic without available treatments and effective vaccines. As the COVID-19 pandemic has approached its culmination, desperate efforts have been made to seek proper treatments and response strategies, and the number of clinical trials has been rapidly increasing. In this time of the pandemic, it is believed that learning lessons from it would be meaningful in preparing for future pandemics. Thus, this study aims at providing a comprehensive landscape of COVID-19 related clinical trials based on the ClinicalTrials.gov database. Materials and methods: Up to 30 March 2020, we identified a total of 147 eligible clinical trials and reviewed the overview of the studies. Results: Until then, the most clinical trials were set up in China. Treatment approaches are the most frequent purpose of the registered studies. Chloroquine, interferon, and antiviral agents such as remdesivir, lopinavir, and ritonavir are agents under investigation in these trials. Conclusions: In this study, we introduced the promising therapeutic options that many researchers and clinicians are interested in, and to address the hidden issues behind clinical trials in this COVID-19 pandemic.
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Ensayos Clínicos como Asunto/estadística & datos numéricos , Infecciones por Coronavirus/terapia , Neumonía Viral/terapia , COVID-19 , Bases de Datos Factuales , Humanos , PandemiasRESUMEN
BACKGROUND: Mental health problems are a growing issue among customer-facing workers. This study aimed to investigate the workers' symptoms of anxiety, depression, and sleep disturbance caused by customer complaints and the suppression of one's emotions at work. METHODS: This study used the data from the fifth Korean Working Conditions Survey 2017 database. The subjects comprised 23,128 workers (men, 11,007; women, 12,121). The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multiple logistic regression models, to determine the effect of the exposure level of engaging with angry clients and suppressing one's emotions at work on mental health. RESULTS: Among the workers engaging with angry customers, compared to the "Rarely" group as a reference point, the "Always" group showed elevated OR values (at [95% CI]) of 1.52 (1.10-2.10), 1.86 (1.05-3.27), 4.43 (3.11-6.33), 3.74 (2.51-5.55), 3.89 (2.65-5.70) for men workers; and 2.86 (1.94-4.22), 2.55 (1.73-3.75), 3.75 (2.82-4.98), 3.81 (2.84-5.09), 3.84 (2.88-5.12) for women workers, for depression, anxiety, difficulty falling asleep, waking up during sleep, and extreme fatigue after waking up, respectively. For suppressing one's emotions at work, the OR values of the "Always" group were 2.32 (1.53-3.51), 2.46 (1.73-3.50), 2.54 (1.88-3.43), 2.64 (1.92-3.64), 2.42 (1.81-3.24) for men workers; and 2.23 (1.53-3.25), 2.31 (1.61-3.33), 2.26 (1.72-2.96), 1.53 (1.19-1.97), 2.15 (1.62-2.85) for women workers, for depression, anxiety, and difficulty falling asleep, waking up during sleep, and extreme fatigue after waking up, respectively. CONCLUSION: The emotional labor demanded from customer-facing workers, incurred by facing customer complaints and suppressing one's emotions at work, was found to be significantly associated with the development of depression, anxiety, and sleep disturbance symptoms among the Korean working population.
Asunto(s)
Ansiedad/diagnóstico , Depresión/diagnóstico , Trastornos del Sueño-Vigilia/diagnóstico , Adulto , Ansiedad/epidemiología , Bases de Datos Factuales , Depresión/epidemiología , Emociones , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , República de Corea/epidemiología , Trastornos del Sueño-Vigilia/epidemiología , Encuestas y Cuestionarios , Lugar de TrabajoRESUMEN
In the last decade, great advances have been made in understanding the genetic basis for focal segmental glomerulosclerosis (FSGS). Animal models using specific gene disruption of the slit diaphragm and cytoskeleton of the foot process mirror the etiology of the human disease. Many animal models have been developed to understand the complex pathophysiology of FSGS. Therefore, we need to know the usefulness and exact methodology of creating animal models. Here, we review classic animal models and newly developed genetic animal models. Classic animal models of FSGS involve direct podocyte injury and indirect podocyte injury due to adaptive responses. However, the phenotype depends on the animal background. Renal ablation and direct podocyte toxin (PAN, adriamycin) models are leading animal models for FSGS, which have some limitations depending on mice background. A second group of animal models were developed using combinations of genetic mutation and toxin, such as NEP25, diphtheria toxin, and Thy1.1 models, which specifically injure podocytes. A third group of animal models involves genetic engineering techniques targeting podocyte expression molecules, such as podocin, CD2-associated protein, and TRPC6 channels. More detailed information about podocytopathy and FSGS can be expected in the coming decade. Different animal models should be used to study FSGS depending on the specific aim and sometimes should be used in combination.