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1.
J Cell Sci ; 136(23)2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37987169

RESUMEN

Tumor cell invasion into heterogenous interstitial tissues consisting of network-, channel- or rift-like architectures involves both matrix metalloproteinase (MMP)-mediated tissue remodeling and cell shape adaptation to tissue geometry. Three-dimensional (3D) models composed of either porous or linearly aligned architectures have added to the understanding of how physical spacing principles affect migration efficacy; however, the relative contribution of each architecture to decision making in the presence of varying MMP availability is not known. Here, we developed an interface assay containing a cleft between two high-density collagen lattices, and we used this assay to probe tumor cell invasion efficacy, invasion mode and MMP dependence in concert. In silico modeling predicted facilitated cell migration into confining clefts independently of MMP activity, whereas migration into dense porous matrix was predicted to require matrix degradation. This prediction was verified experimentally, where inhibition of collagen degradation was found to strongly compromise migration into 3D collagen in a density-dependent manner, but interface-guided migration remained effective, occurring by cell jamming. The 3D interface assay reported here may serve as a suitable model to better understand the impact of in vivo-relevant interstitial tissue topologies on tumor invasion patterning and responses to molecular interventions.


Asunto(s)
Colágeno , Matriz Extracelular , Humanos , Proteolisis , Matriz Extracelular/metabolismo , Invasividad Neoplásica/patología , Colágeno/metabolismo , Movimiento Celular/fisiología
2.
Nanotechnology ; 35(24)2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38271718

RESUMEN

With the advancements in flexible materials and information technology, flexible sensors are becoming increasingly pervasive in various aspects of life and production. They hold immense potential for further development in areas such as motion detection, electronic skin, soft robots, and wearable devices. Aminopropyl-terminated polydimethylsiloxane (PDMS) was used as the raw material, while a diisocyanate reagent served as the cross-linking agent for the polymerization reaction, which involved the introduction of ureido groups, containing N-H and C=O bonds, into the long siloxane chain. The dynamic hydrogen bonding between the clusters completes the self-healing of the material. Using 1-[3-(trimethoxysilyl)propyl]urea as a grafting agent, the urea groups are introduced into graphene oxide and carbon nanotubes (CNTs) as conductive fillers. Subsequently, a flexible polymer is used as the substrate to prepare conductive flexible self-healing composites. By controlling the amount of conductive fillers, flexible strain materials with varying sensitivities are obtained. Design the structure of the flexible strain sensor using three-dimensional (3D) modeling software with deposition printing method.

3.
BMC Public Health ; 24(1): 532, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38378519

RESUMEN

BACKGROUND: Chronic hepatitis C (CHC) virus infection is a global health concern that is associated with significant liver-related morbidity and mortality. Owing to the inflammatory pathway, CHC can causefatty liver, liver cirrhosis, and liver cancer and is associated with cardiometabolic diseases, such as hypertension and diabetes. Fatty liver is associated with metabolic disorders, cardiovascular diseases, diabetes, and liver cancer. Hence, the early detection of fatty liver through noninvasive screening in adults with CHC is important in primary healthcare settings. This study aimed to explore the prevalence of fatty liver and its association with metabolic syndrome amongrural adults with CHC. METHODS: This was a series of cohort studies related to the elimination of the CHC burden around the western coastal Yunlin County, Taiwan, between August 2018 and July 2021. A cross-sectional study was conducted after hepatitis C virus RNA confirmation in a hepatitis C- endemic area. A gastrointestinal physician or radiologist assessed fatty liver by ultrasonography. Fatty liver was classified into four grades: normal, mild, moderate, and severe. Three liver enzyme biomarkers were identified. According to the Taiwan national standard, metabolic syndrome was defined based on the presence of three or more of the five abnormal biomarkers, including increased waist circumference, elevated blood pressure, elevated fasting blood glucose level, elevated triglyceride level, and low high-density lipoprotein cholesterol level. RESULTS: A total of 256 rural adults with CHC were enrolled. The mean age of the participants was 67.5 (standard deviation = 11.8) years, with a low educational level. High prevalence of fatty liver (79%), central obesity (54.3%), elevated blood pressure (55.5%),elevated fasting blood glucose (FBG) level (44.9%), and metabolic syndrome (37.9%) were observed.The results showed that adults with CHC with moderate to severe fatty liver were significantly associated with an increased risk of increased waist circumference (P < 0.001), increased blood pressure (P < 0.001), low high-density lipoprotein cholesterol level (P < 0.05), and elevated liver enzyme biomarker levels (all P < 0.05) after adjusting for age, sex, and educational level. Furthermore, adults with CHC with moderate to severe fatty liver were significantly associated with a greater risk of metabolic syndrome (odds ratio = 2.85, 95% confidence interval = 1.66 to 4.92). CONCLUSIONS: The findings demonstrate a high prevalence of fatty liver in rural adults with CHC, which is significantly associated with obesity, metabolic syndrome, and elevated liver biomarker levels. Clinicians and primary healthcare providers must encourage patients with CHC to receive antiviral therapy combined with weight loss management and lifestyle modification, allowing general improvements in their liver and cardiometabolic health.


Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus , Hígado Graso , Hepatitis C Crónica , Hipertensión , Neoplasias Hepáticas , Síndrome Metabólico , Adulto , Humanos , Niño , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/diagnóstico , Factores de Riesgo , Prevalencia , Glucemia , Estudios Transversales , Hígado Graso/diagnóstico por imagen , Hígado Graso/epidemiología , Obesidad/epidemiología , Hipertensión/complicaciones , Enfermedades Cardiovasculares/complicaciones , Biomarcadores , Colesterol , Lipoproteínas HDL , Atención Primaria de Salud
4.
Aesthetic Plast Surg ; 48(6): 1133-1141, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37253841

RESUMEN

BACKGROUND: The difficulty in creating and maintaining a stable workspace of the breast makes endoscopic nipple-/skin-spring mastectomy (E-N/SSM) develop slowly. This study aims to report the preliminary results of a novel endoscopic technique for N/SSM followed by dual-plane direct-to-implant (DP-DTI) breast reconstruction. METHODS: A prospectively maintained database was reviewed that included patients who underwent single-axillary-incision E-N/SSM and DP-DTI breast reconstruction from September 2020 to April 2021 at a single institution by three surgeons. The data were collected prospectively and analyzed to determine the efficacy, feasibility, safety, and esthetic results of the operation, as well as quality of life (QoL). RESULTS: During the study period, a total of 68 E-N/SSM and DP-DTI reconstruction procedures through a single axillary incision were performed in 63 female patients. Among all the procedures, the majority were performed for grade 1-3 ptotic breasts (n =46, 73.0%). During the median follow-up of 26.5 months, the major and minor surgical complication rates were 1.6% (1/63) and 9.5% (6/63), respectively. The cosmetic complication rate was 14.3%. One patient suffered local recurrence 4 months postoperation. The average scores in patient-reported outcomes at 2 years postoperation of satisfaction with breast (66.57), psychosocial well-being (75.93) and sexual well-being (56.29) were not significantly different compared with the baseline, except for physical well-being: chest (69.85). CONCLUSIONS: The proposed procedure for E-N/SSM and DP-DTI breast reconstruction is feasible, time-saving and safe with good outcomes in terms of cosmetic results and QoL and expands the indications of DTI reconstruction to ptotic breasts, making it easier to popularize. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Asunto(s)
Implantes de Mama , Neoplasias de la Mama , Mamoplastia , Femenino , Humanos , Mastectomía/métodos , Estudios Prospectivos , Pezones/cirugía , Calidad de Vida , Neoplasias de la Mama/cirugía , Mamoplastia/métodos , Estudios Retrospectivos , Resultado del Tratamiento
5.
Artículo en Inglés | MEDLINE | ID: mdl-37695290

RESUMEN

OBJECTIVE: To assess the incidence and risk factors of major adverse cardiovascular events (MACE) in patients with systemic sclerosis (SSc). METHODS: We conducted a nationwide, population-based, cohort study using Taiwan's National Health Insurance Research Database. We performed propensity score matching (PSM) using a 1:2 ratio, resulting in inclusion of 1,379 patients with SSc and 2,758 non-SSc individuals in the analysis. We assessed the association between SSc and MACE using the multivariable Cox proportional hazard regression model with adjustment of time-dependent covariates and investigated risk factors of MACE in patients with SSc, shown as adjusted hazard ratios (aHRs) with 95% confidence intervals (CI). RESULTS: SSc was not significantly associated with the risk of MACE (aHR 1.04; 95% CI 0.77-1.42). Nevertheless, SSc was associated with increased risk of myocardial infarction (IRR 1.76; 95% CI 1.08-2.86) and peripheral arterial occlusion disease (IRR 3.67; 95% CI 2.84-4.74) but not with ischemic stroke (IRR 0.89; 95% CI 0.61-1.29). Factors independently associated with MACE in SSc patients included age (aHR 1.02), male gender (aHR 2.01), living in a suburban area (aHR 2.09), living in a rural area (aHR 3.00), valvular heart disease (aHR 4.26), rheumatoid arthritis (RA) (aHR 2.14), use of clopidogrel (aHR 26.65), and use of aspirin (aHR 5.31). CONCLUSIONS: The risk of MACE was not significantly increased in Taiwanese patients with SSc, and our investigation effectively identified the factors independently associated with MACE in SSc patients. Additionally, patients with SSc exhibited higher risks of MI and PAOD but not ischemic stroke.

6.
J Surg Res ; 277: 148-156, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35490603

RESUMEN

INTRODUCTION: The best strategy for drain removal after mastectomy and axillary surgery in breast cancer patients has remained controversial. We conducted a multicenter, three-arm randomized clinical trial to determine the optimal strategy. METHODS: A total of 187 eligible breast cancer patients who underwent mastectomy and axillary surgery were randomized into 10 mL (n = 62), 20 mL (n = 63), and 30 mL (n = 63) groups for drain removal on the first day when the output decreased to a corresponding volume in 24 h. The drain duration, total drain duration, incidence of seroma, quality of life, outpatient visit times, healthcare costs, and postoperative complications were evaluated. RESULTS: The median axillary drain durations and total drain durations were all significantly different between three groups (both P < 0.001). The incidences of seroma were 31.1%, 38.3%, and 52.1%, and the difference between the 30 mL and 10 mL groups was significant (RR = 2.41). The 20 mL group reported significantly better quality of life (QoL) in terms of physical functioning (PF) at the 2-week (30 mL versus 20 mL, HR:-14.18) and 3-week (20 mL versus 10 mL, HR: 11.65) follow-up and role functioning (RF) at the 2-week follow-up (20 mL versus 10 mL, HR: 18.15). No between-group differences were found in G-QoL, outpatient visits, costs, or complications. CONCLUSIONS: The 20 mL group had a moderate drain duration, total drain duration, and incidence of seroma but a significant advantage over the other two groups in terms of PF and RF, with relatively low outpatient costs and comparable postoperative complication rates. These findings could aid in clinical decision-making regarding drain removal timing (http://www.chictr.org.cn/: ChiCTR2000028729).


Asunto(s)
Neoplasias de la Mama , Mastectomía , Axila/cirugía , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/cirugía , Drenaje/efectos adversos , Femenino , Humanos , Mastectomía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Calidad de Vida , Seroma/epidemiología , Seroma/etiología
7.
Breast J ; 2022: 1373899, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36349179

RESUMEN

Background: Endoscopic nipple- or skin-sparing mastectomy (E-N/SSM) and endoscopic latissimus dorsi muscle flap (E-LDMF) harvest have been operational difficulties over decades. The aim of this study was to describe the preliminary outcomes of our novel surgical technique, which allows the performance of E-N/SSM and E-LDMF harvest for immediate breast reconstruction (IBR) through a single cosmetic axillary incision for breast cancer patients. Methods: This prospective study included 20 breast cancer patients who underwent E-N/SSM and E-LDMF harvesting through a single axillary incision in our hospital from September 2020 to June 2022. The outcomes were statistically calculated, including patient characteristics, operative data, complication rate, hospital length of stay and costs, and patient-reported outcomes. Results: A total of 20 breast cancer patients underwent our sufficiently mature novel endoscopy technique. The mean LD flap harvest time was 96.5 ± 25.3 min, the mean operation time was 262.6 ± 54.4 min, and the average length of LDMF was 26.9 ± 3.1. During the median follow-up time of 7.5 months, 4 patients developed donor-site seroma. One of them was also complicated by hypopigmentation of the nipple areola, and one of them suffered from breast cellulitis. No bleeding or flap necrosis happened. No tumor recurrence or metastasis was found until the last follow-up. In the BREAST-Q evaluation, although they gave a lower score beginning at 1-month post-operation than preoperatively (P > 0.05, except for physical well-being: chest and physical well-being: back and shoulder, P < 0.01), there was an uptrend at 3 months postoperatively. Because of the hidden and short incision, the mean score of the appearance scale of the SCAR-Q at 3 months post-operation was 74.2 ± 8.8. Conclusions: The novel endoscopy technique, which was first reported to perform lymph node surgery, N/SSM, and LDMF harvesting in an operation for breast cancer patients through a single axillary incision, is associated with a shorter surgery time, lower complication rates, and better patient-reported outcomes.


Asunto(s)
Neoplasias de la Mama , Mamoplastia , Músculos Superficiales de la Espalda , Humanos , Femenino , Mastectomía/métodos , Pezones/cirugía , Pezones/patología , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Músculos Superficiales de la Espalda/cirugía , Estudios Prospectivos , Recurrencia Local de Neoplasia/cirugía , Mamoplastia/efectos adversos , Mamoplastia/métodos , Endoscopía/efectos adversos , Endoscopía/métodos
8.
Aesthetic Plast Surg ; 46(1): 91-98, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34424367

RESUMEN

BACKGROUND: Although video-assisted breast surgery is gaining popularity, endoscopic reconstruction after mastectomy is still facing lots of problems, bring about that endoscopic method has not yet become a standard procedure for breast cancer reconstruction. Here, we introduce a novel surgical technique of video-assisted transaxillary nipple-sparing mastectomy and immediate implant-based breast reconstruction and describe the detailed surgical procedure using this technique. METHODS: Detailed steps of surgical procedure, the patient characteristics and the mean operative time of this new technique were described in this article. All patients were asked to score their satisfaction with their reconstructed breasts preoperatively, 1 month, 3 months, 6 months and 12 months postoperatively using the BREAST-Q. RESULTS: At first, we used our "conventional method" and performed on 10 patients from April 2017 to June 2020; the operative time was 324.80 ± 66.39 minutes. After improving several procedures of the technique, the "optimized method" was performed on 14 cases from July 2020 to November 2020; the operative time decreased to 193.71 ± 28.75 minutes with shortest was 133 minutes; the optimized method was novel and easy to learn and be generalized. Most of the patients were satisfied with the reconstruction results. There was no significant difference between preoperative scores and scores at 3 months, 6 months and 12 months (p = 0.364). Since there is no wound on the breast dome, no obvious postoperative complications were observed except for one patient presented with infection. CONCLUSIONS: This new technique has allowed surgeons to achieve excellent and reproducible outcomes in a single-stage procedure and represents an excellent technique for patients who wish to have a scarless and aesthetically pleasing appearance after mastectomy for breast cancer. This article also highlights the mean operative time (193.71 ± 28.75 minutes) that has been made possible with this new technique. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .


Asunto(s)
Neoplasias de la Mama , Mamoplastia , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mamoplastia/métodos , Mastectomía/métodos , Pezones/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
9.
J Clin Rheumatol ; 28(2): e633-e637, 2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-34371515

RESUMEN

BACKGROUND: Mycophenolate mofetil (MMF) is extensively used for induction and maintenance therapy in patients with lupus nephritis (LN). Enteric-coated mycophenolate sodium (EC-MPS) was developed to reduce the adverse gastrointestinal effects of MMF. However, the therapeutic efficacy of MMF and EC-MPS in LN remains unclear. This study aimed to examine the treatment effects of EC-MPS in LN patients with prior MMF exposure. METHODS: In this medical records review study, we included 54 LN patients, of whom 34 converted from MMF to EC-MPS at equimolar doses in 2016-2018 (nonmedical switching group) and 20 received continuous MMF treatment. Patients achieving complete remission or partial remission before the conversion were categorized as responders, whereas those who had never achieved complete remission or partial remission were categorized as nonresponders. RESULTS: Baseline proteinuria was higher in the nonmedical switching group. Although elevation in proteinuria was observed after nonmedical switching, the serum creatinine concentration and estimated glomerular filtration rate both improved. Responders in the nonmedical switching group had lower proteinuria and higher complement 3 levels. In the subgroup analysis, albeit the modest increase in daily urine protein, anti-double-stranded DNA antibody levels, estimated glomerular filtration rate, and complements 3 and 4 seemed comparable after conversion. CONCLUSION: Switching to EC-MPS demonstrated a similar short-term renal response to continuous MMF treatment in LN patients. Prospective randomized trials are required to verify our findings.


Asunto(s)
Trasplante de Riñón , Nefritis Lúpica , Anticuerpos Antinucleares , Humanos , Inmunosupresores/efectos adversos , Trasplante de Riñón/efectos adversos , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/tratamiento farmacológico , Ácido Micofenólico/uso terapéutico , Estudios Prospectivos , Comprimidos Recubiertos
10.
J Gastroenterol Hepatol ; 36(10): 2911-2916, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33978973

RESUMEN

BACKGROUND: Pangenotypic direct-acting antiviral agents (DAAs) glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL) are effective against all hepatitis C virus (HCV) genotype infections. However, data on pangenotypic DAA treatment for mixed genotype HCV infection are sparse. METHODS: This is a retrospective, single site cohort study analyzing all patients with mixed HCV genotype infections treated with GLE/PIB or SOF/VEL from August 2018 to August 2020 in Chiayi Chang Gung Memorial Hospital, Taiwan. The primary study endpoint was sustained virologic response (SVR) 12 weeks after treatment cessation. We also reported adverse events (AEs). RESULTS: A total of 108 patients with mixed infections of any two or three genotypes of 1a, 1b, 2, 3, and 6 received pangenotypic DAAs during the study period. A total of 67 patients received GLE/PIB and 41 received SOF/VEL. The evaluable population analysis revealed SVR rates of 94% (63/67) and 95.1% (39/41) for GLE/PIB and SOF/VEL therapy, respectively, and the per-protocol analysis revealed an SVR of 100% for both regimens. Four patients in the GLE/PIB group and two patients in the SOF/VEL were lost to follow-up. The most common AEs for GLE/PIB versus SOF/VEL therapy included pruritus (14.9% vs 2.4%), fatigue (6.0% vs 7.3%), abdominal discomfort (4.5% vs 7.3%), and acid reflux (3.0% vs 4.9%). DAA-related significant laboratory abnormalities occurred in three patients with > 1.5 × elevated bilirubin level in the GLE/PIB group. None of the above AEs resulted in DAA discontinuation. CONCLUSIONS: Pangenotypic DAAs are well tolerated by and yield high SVR rates in patients with mixed genotype HCV infection.


Asunto(s)
Hepatitis C Crónica , Hepatitis C , Antivirales/efectos adversos , Estudios de Cohortes , Genotipo , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Estudios Retrospectivos , Sofosbuvir/efectos adversos , Respuesta Virológica Sostenida , Resultado del Tratamiento
11.
J Formos Med Assoc ; 120(2): 847-853, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32896456

RESUMEN

BACKGROUND/PURPOSE: Low viral load (LVL) of hepatitis B virus (HBV) is a predictor of chronic HBV infection. However, the usefulness of quantitative hepatitis B surface antigen (qHBsAg) in predicting LVL in community-based screening has not been well studied. We aimed to measure the prevalence of LVL in HBV carriers and validate the efficacy of qHBsAg in predicting LVL. METHODS: This community-based screening study was conducted in Taiwan. HBV DNA was assayed in HBsAg carriers. Participants were randomized to training and validation sets to determine the ability of qHBsAg to predict LVL. Receiver operating characteristic curves were used to identify the best cutoff values in the training set. RESULTS: Among the 2919 participants, 359 (12.2%) were HBsAg carriers. There were 132 and 137 carriers in the training and validation sets, respectively. Significant correlations were found between qHBsAg and HBV DNA in both training and validation sets. Thirty and 29 participants with qHBsAg <8 IU/mL in the training and validation sets, respectively, had LVL. Using 8 IU/mL as the cutoff, negative predictive value (NPV) of qHBsAg for HBV DNA levels >2000 IU/mL was 100%. The best cutoff level of qHBsAg to predict HBV LVL was 200 IU/mL, with a sensitivity, specificity, and accuracy of 75.0%, 76.1%, and 75.8%, respectively, in the training set. The positive predictive value and NPV were 70.0% and 77.9%, respectively, in the validation set. CONCLUSION: Approximately 60% of HBsAg carriers had HBV LVL, and qHBsAg <8 IU/mL accurately predicts LVL. This quantitative test provides additional information for community-based screening.


Asunto(s)
Hepatitis B , ADN Viral , Hepatitis B/diagnóstico , Antígenos de Superficie de la Hepatitis B , Antígenos e de la Hepatitis B , Virus de la Hepatitis B/genética , Humanos , Taiwán , Carga Viral
12.
J Formos Med Assoc ; 120(1 Pt 2): 542-550, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32669233

RESUMEN

BACKGROUND/PURPOSE: Multiple sclerosis is classified as a rare disease in Taiwan. This study evaluated the safety and effectiveness of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) from routine clinical practice in Taiwan. METHODS: In this retrospective, multicentre, observational study, we collected clinical data of patients treated with fingolimod 0.5 mg/day in routine clinical practice between September 2012 and December 2015. Primary outcome was the overall safety of fingolimod; secondary outcome was the annualized relapse rate (ARR). RESULTS: Overall, 62/69 (86.1%) patients were on fingolimod by the end of data collection period. Mean age (±standard deviation [SD]) at inclusion was 37.7 ± 10.10 years; mean duration of MS was 5.4 ± 4.52 years and mean duration of fingolimod exposure was 135.8 patient-years. The most common adverse events (AEs) were bradycardia (21.7%; first-dose related), upper respiratory tract infection, dizziness, and hypoaesthesia (numbness) (11.6% each), followed by urinary tract infection and back pain (7.2% each). Seven patients had liver enzyme-related AEs. Eight patients had absolute lymphocyte counts <0.2 × 103/uL over the study period. One patient developed second degree AV block after first-dosing. Serious AEs were observed in 11 patients (15.9%; mild-to-moderate). No newly developed macular oedema was detected. The ARR was 0.3 ± 0.74 in fingolimod-treated patients and 66.7% of patients were relapse-free. The mean (SD) change from baseline in expanded disability status scale score was -0.30 ± 1.353. CONCLUSION: Fingolimod 0.5 mg/day treatment with an average of 2 years of exposure was associated with a manageable safety profile, and maintained/improved effectiveness in RRMS patients from Taiwan.


Asunto(s)
Clorhidrato de Fingolimod/uso terapéutico , Esclerosis Múltiple , Adulto , Clorhidrato de Fingolimod/efectos adversos , Humanos , Inmunosupresores/efectos adversos , Persona de Mediana Edad , Esclerosis Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Taiwán
13.
Int J Mol Sci ; 22(3)2021 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-33572934

RESUMEN

(1) Background: Antifolate methotrexate (MTX) is the most common disease-modifying antirheumatic drug (DMARD) for treating human rheumatoid arthritis (RA). The mitochondrial-produced formate is essential for folate-mediated one carbon (1C) metabolism. The impacts of MTX on formate homeostasis in unknown, and rigorously controlled kinetic studies can greatly help in this regard. (2) Methods: Combining animal model (8-week old female C57BL/6JNarl mice, n = 18), cell models, stable isotopic tracer studies with gas chromatography/mass spectrometry (GC/MS) platforms, we systematically investigated how MTX interferes with the partitioning of mitochondrial and cytosolic formate metabolism. (3) Results: MTX significantly reduced de novo deoxythymidylate (dTMP) and methionine biosyntheses from mitochondrial-derived formate in cells, mouse liver, and bone marrow, supporting our postulation that MTX depletes mitochondrial 1C supply. Furthermore, MTX inhibited formate generation from mitochondria glycine cleavage system (GCS) both in vitro and in vivo. Folinate selectively rescued 1C metabolic pathways in a tissue-, cellular compartment-, and pathway-specific manner: folinate effectively reversed the inhibition of mitochondrial formate-dependent 1C metabolism in mouse bone marrow (dTMP, methionine, and GCS) and cells (dTMP and GCS) but not methionine synthesis in liver/liver-derived cells. Folinate failed to fully recover hepatic mitochondrial-formate utilization for methionine synthesis, suggesting that the efficacy of clinical folinate rescue in MTX therapy on hepatic methionine metabolism is poor. (4) Conclusion: Conducting studies in mouse and cell models, we demonstrate novel findings that MTX specifically depletes mitochondrial 1C supply that can be ameliorated by folinate supplementation except for hepatic transmethylation. These results imply that clinical use of low-dose MTX may particularly impede 1C metabolism via depletion of mitochondrial formate. The MTX induced systematic and tissue-specific formate depletion needs to be addressed more carefully, and the efficacy of folinate with respect to protecting against such depletion deserves to be evaluated in medical practice.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Formiatos/metabolismo , Leucovorina/uso terapéutico , Metotrexato/uso terapéutico , Complejo Vitamínico B/uso terapéutico , Animales , Antirreumáticos/farmacología , Artritis Reumatoide/metabolismo , Suplementos Dietéticos , Femenino , Humanos , Leucovorina/farmacología , Redes y Vías Metabólicas/efectos de los fármacos , Metotrexato/farmacología , Ratones Endogámicos C57BL , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Complejo Vitamínico B/farmacología
14.
J Viral Hepat ; 27(9): 866-872, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32343472

RESUMEN

Data on direct-acting antiviral agent (DAA) treatment for mixed genotype hepatitis C virus (HCV) infection are scant. This study examined the effectiveness of glecaprevir/pibrentasvir (GLE/PIB) and ledipasvir/sofosbuvir (LDV/SOF) for mixed HCV genotype infection in a real-world setting in Taiwan. We analysed the data from all patients with mixed HCV genotype infections treated with GLE/PIB or LDV/SOF from 2017 to 2019 in three Chang Gung Memorial Hospitals in Taiwan. The primary treatment outcome was sustained virologic response 12 weeks after treatment cessation (SVR12). Adverse events (AEs) were also evaluated. A total of 5190 HCV patients received DAA treatment during this time period. Among them, 116 patients (2.2%) had mixed infections of any 2 or 3 genotypes of 1a, 1b, 2, 3 and 6. Fifty-four patients received GLE/PIB and 62 received LDV/SOF. SVR12 rates for LDV/SOF vs GLE/PIB therapy were 96.6% (56/58) vs 100% (51/51) by the per-protocol analysis and 90.3% (56/62) vs 94.4% (51/54) by the evaluable population analysis. Two patients with 1b + 6 and 1b + 2 genotype infections in the LDV/SOF group had relapse. Evaluating the GLE/PIB vs LDV/SOF groups for the most common AEs revealed pruritus (16.7% vs 4.8%), abdominal discomfort (5.6% vs 8%) and fatigue (5.6% vs 4.8%). One patient with AE-related treatment discontinuation presented with liver decompensation after 4-week GLE/PIB therapy. DAA-related significant laboratory abnormalities occurred in two patients with >3× elevated bilirubin level in the GLE/PIB group. GLE/PIB and LDV/SOF are well tolerated and achieve high SVR12 rates for patients with mixed HCV genotype infection.


Asunto(s)
Antivirales , Hepatitis C Crónica , Hepatitis C , Ácidos Aminoisobutíricos/uso terapéutico , Antivirales/uso terapéutico , Bencimidazoles/uso terapéutico , Ciclopropanos/uso terapéutico , Fluorenos/uso terapéutico , Genotipo , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Lactamas Macrocíclicas/uso terapéutico , Leucina/análogos & derivados , Leucina/uso terapéutico , Prolina/análogos & derivados , Prolina/uso terapéutico , Pirrolidinas/uso terapéutico , Quinoxalinas/uso terapéutico , Sofosbuvir/uso terapéutico , Sulfonamidas/uso terapéutico , Respuesta Virológica Sostenida , Taiwán
15.
Rheumatology (Oxford) ; 59(11): 3201-3210, 2020 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-32215624

RESUMEN

OBJECTIVE: Hyperspectral imaging (HSI) is a novel technology for obtaining quantitative measurements from transcutaneous spatial and spectral information. In patients with SSc, the severity of skin tightness is associated with internal organ involvement. However, clinical assessment using the modified Rodnan skin score is highly variable and there are currently no universal standardized protocols. This study aimed to compare the ability to differentiate between SSc patients and healthy controls using skin scores, ultrasound and HSI. METHODS: Short-wave infrared light was utilized to detect the spectral angle mapper (SAM) of HSI. In addition, skin severity was evaluated by skin scores, ultrasound to detect dermal thickness and strain elastography. Spearman's correlation was used for assessing skin scores, strain ratio, thickness and SAM. Comparisons of various assessment tools were performed by receiver operating characteristic curves. RESULTS: In total, 31 SSc patients were enrolled. SAM was positively correlated with skin scores and dermal thickness. In SSc patients with normal skin scores, SAM values were still significantly higher than in healthy controls. SAM exhibited the highest area under the curve (AUC: 0.812, P < 0.001) in detecting SSc compared with skin scores (AUC: 0.712, P < 0.001), thickness (AUC: 0.585, P = 0.009) and strain ratio by elastography (AUC: 0.522, P = 0.510). Moreover, the severity of skin tightness was reflected by the incremental changes of waveforms in the spectral diagrams. CONCLUSION: SAM was correlated with skin scores and sufficiently sensitive to detect subclinical disease. HSI can be used as a novel, non-invasive method for assessing skin changes in SSc.


Asunto(s)
Imágenes Hiperespectrales , Esclerodermia Sistémica/diagnóstico , Enfermedades de la Piel/diagnóstico , Adulto , Estudios de Cohortes , Diagnóstico por Imagen de Elasticidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Esclerodermia Sistémica/complicaciones , Índice de Severidad de la Enfermedad , Enfermedades de la Piel/diagnóstico por imagen , Enfermedades de la Piel/etiología
16.
Chem Rec ; 20(8): 773-792, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32154653

RESUMEN

The properties of polyvinyl alcohol (PVA) nanocomposite hydrogels influenced by nanoparticles are reviewed. Various kinds of nanoparticles with excellent mechanical and electrical properties have been introduced into PVA hydrogel to produce stretchable and conductive PVA nanocomposite hydrogel. Understanding the mechanism between the matrix of PVA hydrogel and nanoparticles is therefore critical for the development of PVA nanocomposite hydrogels. This review focuses on the nanoparticles include carbon nanotubes, graphene oxide and metal nanoparticles, and describes the effects of nanoparticles on the mechanical and conductive properties of PVA nanocomposite hydrogels. A new promising area of soft stretchable PVA nanocomposite hydrogel is highlighted for possible applications. Finally, a brief outlook for future research is presented.

17.
Int J Syst Evol Microbiol ; 70(1): 100-104, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31535968

RESUMEN

A Gram-stain-negative, aerobic and curved-rod-shaped bacterium, designated QM202T, was isolated from red algae (Gracilaria blodgettii). Cells of strain QM202T were 0.2-0.3 µm wide and 1.0-2.5 µm long, catalase-negative and oxidase-positive. The strain exhibited an agar-degrading activity. It was motile by means of a single polar flagellum. Optimal growth occurred at 28-30 °C, pH 7.0-7.5 and in the presence of 2.0-3.0 % (w/v) NaCl. The DNA G+C content was 41.4 mol%. The isoprenoid quinone was identified as Q-8. Phophatidylethanolamine and phosphatidylglycerol were the predominant phospholipids. The dominant fatty acids were C18:1ω7c, C16:0 and C16:1ω7c and/or iso-C15:0 2-OH. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain QM202T belonged to the genus Marinomonas. The closest described neighbour in terms of 16S rRNA gene sequence identity was Marinomonas blandensis MED121T (95.5 %). The differential phenotypic properties, together with the phylogenetic and genetic distinctiveness indicated that strain QM202T can be considered to represent a novel species, Marinomonas agarivorans sp. nov. The type strain is QM202T (=KCTC 52475T=MCCC 1H00145T).


Asunto(s)
Gracilaria/microbiología , Marinomonas/clasificación , Filogenia , Agar , Alteromonadaceae/clasificación , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Ácidos Grasos/química , Marinomonas/aislamiento & purificación , Océanos y Mares , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN
18.
J Nurs Scholarsh ; 52(2): 128-135, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31750620

RESUMEN

PURPOSE: To explore the prevalence of hepatitis C virus (HCV) infection as well as the levels of liver health literacy and association with the health status of people with HCV through the nurse-led community health development goal of global elimination. METHODS: A community-based, cross-sectional study was conducted between July 2018 and June 2019 in coastal Western Yunlin County, Taiwan. This study was conducted at five townships, and serum HCV antibody (anti-HCV) screening was used for the identification of potentially infected people by a collaborating local hospital. RESULTS: Of the 1,963 adults from rural areas enrolled in this study, 321 (16.4%) were anti-HCV positive, 237 (73.8%) reported that they were unaware of their HCV positivity, and none of them were provided information on direct-acting antiviral agent therapy. The levels of anti-HCV positivity were higher among female patients (p < .05), elderly people (p < .001), those with a low education level (p < .001), and those from the Sihu Township within Yunlin County (p < .001). Participants with anti-HCV positivity tended to have lower intakes of vegetables (p < .01) and fruit (p < .05), a greater number of comorbidities (p < .05), as well as a greater incidence of abnormal liver (p < .001) and renal function (p < .001) compared to those with anti-HCV negativity. Multivariable linear regression analysis showed that the presence of HCV infection and a greater number of metabolic syndrome components were associated with poor liver and renal function. CONCLUSIONS: These findings showed a high prevalence of HCV infection among adults living in rural areas, who had low literacy levels on hepatitis, unhealthy lifestyles, and abnormal liver and renal function. CLINICAL RELEVANCE: Clinicians and primary healthcare providers should initiate efforts to increase the levels of liver health literacy by increasing the accessibility to infection confirmation tests and reducing the number of barriers to the reception of antiviral treatment.


Asunto(s)
Alfabetización en Salud , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/enfermería , Enfermería/métodos , Educación del Paciente como Asunto/métodos , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/uso terapéutico , Servicios de Salud Comunitaria/organización & administración , Estudios Transversales , Dieta , Erradicación de la Enfermedad , Femenino , Salud Global , Educación en Salud/organización & administración , Conocimientos, Actitudes y Práctica en Salud , Estado de Salud , Hepacivirus , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C Crónica/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Prevalencia , Población Rural , Taiwán/epidemiología , Adulto Joven
19.
J Formos Med Assoc ; 119(11): 1593-1600, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32839045

RESUMEN

BACKGROUND: The real-world data of glecaprevir/pibrentasvir (GLE/PIB) therapy for patients with chronic hepatitis C virus (HCV) genotype 2 infection remained limited. We aimed to evaluate the possible predictors of virological failure and side effects of GLE/PIB therapy for chronic genotype 2 HCV-infected patients in a real-world setting. METHODS: A total of 326 compensated HCV genotype 2 patients treated with GLE/PIB 12 weeks for cirrhotic patients (n = 56) and 8 weeks for non-cirrhotic patients (n = 270) were enrolled. RESULTS: The sustained virological response 12 weeks off therapy (SVR12) was 98.1%, 100%, and 97.7% in overall, GLE/PIB 12-week, and 8-week group, respectively. There were 6 (1.8%) patients with early withdrawal, and 14.1% patients had pruritus, the major adverse effect. In multivariate analyses, end-stage renal disease (odds ratio (OR) = 4.056, 95% confidence interval (CI) = 1.477-11.14, p = 0.007) and hypertension (OR = 2.325, 95% CI = 1.171-4.616, p = 0.016) were two significant factors associated with pruritus. There were 6 patients with virologic failure. In patients receiving 8-week GLE/PIB therapy, the SVR12 rate was significant lower in high baseline viral load (≥107 IU/ml) group compared to low viral load group (90.6% v.s 98.7%, p = 0.025). Multivariate analyses showed that HCV RNA≥107 IU/ml was one of the independent factors (OR = 0.134, 95% CI = 0.024-0.748; p = 0.022) associated with SVR12. CONCLUSION: GIE/PIB is an effective, tolerable and safe agent to treat genotype 2 HCV infected patients. However, high viral load (≥107 IU/ml) may predict virologic failure in non-cirrhotic patients receiving 8 weeks GIE/PIB treatment. This result should be further validated in a large cohort in the future.


Asunto(s)
Ácidos Aminoisobutíricos/uso terapéutico , Bencimidazoles/uso terapéutico , Ciclopropanos/uso terapéutico , Hepatitis C Crónica , Lactamas Macrocíclicas/uso terapéutico , Leucina/análogos & derivados , Prolina/análogos & derivados , Quinoxalinas/uso terapéutico , Sulfonamidas/uso terapéutico , Antivirales/efectos adversos , Bencimidazoles/orina , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Leucina/uso terapéutico , Prolina/uso terapéutico , Pirrolidinas , Carga Viral
20.
Appl Nurs Res ; 55: 151333, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32739072

RESUMEN

AIM: The aim of this study was to explore the effectiveness of an oral hygiene program combined with home-phone health promoting counseling for rural adults with metabolic syndrome. BACKGROUND: Metabolic syndrome is an important risk factor for cardiometabolic diseases. Evidence indicates that the poor oral hygiene and unhealthy lifestyles are closely related to metabolic syndrome. METHODS: A prospective quasi-experimental design involved a total of 136 community adults, with metabolic syndrome living in two rural townships, were clustered and conveniently assigned to intervention and control group between June 2017 and December 2018. The primary outcome was the change in cardiometabolic biomarkers. The secondary outcome comprised changes in the health-promoting behaviors. The intervention effect was assessed using a generalized estimating equation model. RESULTS: There were 80 and 56 participants in the intervention and control group, respectively. The mean age was 56 years and ranged from 33 to 70 years. The intervention group exhibited a greater improvement in body mass index (P < 0.01), waist circumference (P < 0.05), body fat percentage (P < 0.05), triglyceride level (P < 0.05), use of dental floss (P < 0.05), regular tooth scaling (P < 0.05), physical activity (P < 0.001), and total score of health-promoting behaviors (P < 0.001) than the control group. CONCLUSION: This study supports the use of an oral hygiene program combined with home-phone counseling, which offers more advantages than its counterpart. Considering the global epidemic of cardiometabolic diseases, this is a community health nursing model worth to replicate and evaluate. Further study should consider innovative strategies to improve the awareness and adoption of a healthy lifestyle in residents with cardiometabolic risks.


Asunto(s)
Enfermedades Cardiovasculares , Síndrome Metabólico , Adulto , Anciano , Enfermedades Cardiovasculares/prevención & control , Consejo , Humanos , Estilo de Vida , Persona de Mediana Edad , Higiene Bucal , Estudios Prospectivos , Proyectos de Investigación , Factores de Riesgo
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