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1.
BMC Cardiovasc Disord ; 23(1): 272, 2023 05 23.
Article in English | MEDLINE | ID: mdl-37221514

ABSTRACT

BACKGROUND: Little research has been done on ischemic outcomes related to left ventricular ejection fraction (EF) in acute decompensated heart failure (ADHF). METHODS: A retrospective cohort study was conducted between 2001 and 2021 using the Chang Gung Research Database. ADHF Patients discharged from hospitals between January 1, 2005, and December 31, 2019. Cardiovascular (CV) mortality and heart failure (HF) rehospitalization are the primary outcome components, along with all-cause mortality, acute myocardial infarction (AMI) and stroke. RESULTS: A total of 12,852 ADHF patients were identified, of whom 2,222 (17.3%) had HFmrEF, the mean (SD) age was 68.5 (14.6) years, and 1,327 (59.7%) were males. In comparison with HFrEF and HFpEF patients, HFmrEF patients had a significant phenotype comorbid with diabetes, dyslipidemia, and ischemic heart disease. Patients with HFmrEF were more likely to experience renal failure, dialysis, and replacement. Both HFmrEF and HFrEF had similar rates of cardioversion and coronary interventions. There was an intermediate clinical outcome between HFpEF and HFrEF, but HFmrEF had the highest rate of AMI (HFpEF, 9.3%; HFmrEF, 13.6%; HFrEF, 9.9%). The AMI rates in HFmrEF were higher than those in HFpEF (AHR, 1.15; 95% Confidence Interval, 0.99 to 1.32) but not in HFrEF (AHR, 0.99; 95% Confidence Interval, 0.87 to 1.13). CONCLUSION: Acute decompression in patients with HFmrEF increases the risk of myocardial infarction. The relationship between HFmrEF and ischemic cardiomyopathy, as well as optimal anti-ischemic treatment, requires further research on a large scale.


Subject(s)
Heart Failure , Myocardial Infarction , Myocardial Ischemia , Male , Female , Humans , Stroke Volume , Retrospective Studies , Ventricular Function, Left , Cohort Studies
2.
Int J Mol Sci ; 24(8)2023 Apr 14.
Article in English | MEDLINE | ID: mdl-37108450

ABSTRACT

(1) To investigate the functional and anatomical outcomes of anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with exudative age-related macular degeneration (AMD) with or without obstructive sleep apnea (OSA); (2) In total, 65 patients with AMD with or without OSA who received three consecutive doses of intravitreal anti-VEGF injections were enrolled. The primary outcomes-best-corrected visual acuity (BCVA) and central macular thickness (CMT)-were assessed at 1 and 3 months. Moreover, morphological changes observed through optical coherence tomography were analyzed; (3) In total, 15 of the 65 patients had OSA and were included in the OSA group; the remaining 50 patients were included in the non-OSA (control) group. At 1 and 3 months after treatment, BCVA and CMT had improved but did not differ significantly between the groups. More patients in the OSA group demonstrated subretinal fluid (SRF) resorption at 3 months after treatment than in the non-OSA group (p = 0.009). Changes in other imaging biomarkers, such as intraretinal cysts, retinal pigment epithelium detachment, hyperreflective dots, and ellipsoid zone disruptions, did not differ significantly between the groups; (4) Our results suggest that the BCVA and CMT outcomes 3 months after anti-VEGF treatment are similar between patients with and without OSA. Moreover, patients with OSA may exhibit superior SRF resorption. A large-scale prospective study is mandatory to evaluate the association between SRF resorption and visual outcomes in AMD patients with OSA.


Subject(s)
Macular Degeneration , Sleep Apnea, Obstructive , Humans , Ranibizumab/therapeutic use , Angiogenesis Inhibitors/therapeutic use , Vascular Endothelial Growth Factor A , Prospective Studies , Vascular Endothelial Growth Factors , Macular Degeneration/complications , Macular Degeneration/drug therapy , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/drug therapy , Tomography, Optical Coherence/methods , Treatment Outcome
3.
Neural Comput ; 34(11): 2273-2293, 2022 10 07.
Article in English | MEDLINE | ID: mdl-36112912

ABSTRACT

Humans have an exceptional ability to extract specific audio streams of interest in a noisy environment; this is known as the cocktail party effect. It is widely accepted that this ability is related to selective attention, a mental process that enables individuals to focus on a particular object. Evidence suggests that sensory neurons can be modulated by top-down signals transmitted from the prefrontal cortex. However, exactly how the projection of attention signals to the cortex and subcortex influences the cocktail effect is unclear. We constructed computational models to study whether attentional modulation is more effective at earlier or later stages for solving the cocktail party problem along the auditory pathway. We modeled the auditory pathway using deep neural networks (DNNs), which can generate representational neural patterns that resemble the human brain. We constructed a series of DNN models in which the main structures were autoencoders. We then trained these DNNs on a speech separation task derived from the dichotic listening paradigm, a common paradigm to investigate the cocktail party effect. We next analyzed the modulation effects of attention signals during all stages. Our results showed that the attentional modulation effect is more effective at the lower stages of the DNNs. This suggests that the projection of attention signals to lower stages within the auditory pathway plays a more significant role than the higher stages in solving the cocktail party problem. This prediction could be tested using neurophysiological experiments.


Subject(s)
Auditory Cortex , Speech Perception , Acoustic Stimulation/methods , Attention/physiology , Auditory Cortex/physiology , Auditory Pathways , Auditory Perception/physiology , Humans , Neural Networks, Computer , Speech Perception/physiology
4.
Psychooncology ; 30(6): 919-927, 2021 06.
Article in English | MEDLINE | ID: mdl-33724591

ABSTRACT

OBJECTIVE: Data regarding the prevalence of depression and anxiety among cancer patients, especially before cancer diagnosis, remains scarce. This study investigated the prevalence of these conditions and associated drug use among cancer patients pre- and post-diagnosis. METHODS: This population-based cohort study using data from Taiwan's National Health Insurance Research Database recruited patients with a registered cancer diagnosis and matched control between January 1, 2000, and December 31, 2011. We compared the prevalence of anxiety and depressive disorders between cancer patients and non-cancer participants during a 2-year period both pre- and post-diagnosis by Pearson's chi-square test. Psychiatric medication use was also examined for the associated mental condition. RESULTS: We examined participants diagnosed with liver (N = 17,154), colorectal (N = 30,391), breast (N = 40,036), gynecological (N = 23,218), and lung (N = 15,671) cancer. Before the cancer diagnosis, the prevalence of depression was higher in non-cancer participants than in gynecological cancer patients (p = 0.018) but anxiety is higher in liver, colorectal, and lung cancer patients when compared to non-cancer participants (p < 0.05). After the cancer diagnosis, the prevalence of anxiety and depression became significantly higher in all enrolled cancer patients than non-cancer participants (p < 0.05). Similar results were observed in psychiatric medication use trends. CONCLUSIONS: This study proposed that patients with liver, colorectal, and lung cancer had an increased risk of developing anxiety, which might be a sentinel diagnosis. The participants had a significantly higher level of anxiety and depressive disorder post-diagnosis, which highlights the importance of the care for both mental and physical conditions in cancer management.


Subject(s)
Depressive Disorder , Neoplasms , Pharmaceutical Preparations , Anxiety/epidemiology , Anxiety Disorders/epidemiology , Cohort Studies , Depressive Disorder/drug therapy , Depressive Disorder/epidemiology , Humans , Neoplasms/epidemiology , Prevalence
5.
J Formos Med Assoc ; 120(8): 1591-1601, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33323325

ABSTRACT

BACKGROUND/PURPOSE: Sapoviruses (SaVs) become important pathogens causing both sporadic and outbreaks of acute gastroenteritis (AGE) after rotavirus vaccination era worldwide. SaVs were included in AGE screening items when norovirus and rotavirus were negative in Taiwan CDC since 2008. However, no complete SaV genome sequence of any genotype detected in Taiwan was determined. This study aimed to investigate SaVs infection and complete genome sequences detected in Taiwan. METHODS: This prospective survey, SaVs samples with untyped or weak PCR result were selected for testing the new design qRT-PCR assay from AGE hospitalized children during 2008-2011, 2016-2017 and AGE outbreak in 2012-2014. Those were genetically characterized using long RT-PCR with different primer combinations as well as primer independent deep sequencing and with 5' RACE and 3' terminal region targeting RT-PCR. RESULTS: Overall, 14 SaV-AGE hospitalized children and 4 SaV-AGE outbreaks were enrolled in this study. In addition to the AGE symptoms, 6 children also showed URI symptoms (cough, pharyngitis, rhinorrhea and nasal congestion). The detected 19 SaVs were classified as eight genotypes (GI.1, GI.2, GI.3, GII.2, GII.3, GII.5, GII.8, and GIV.1) and the complete genome sequence of representative strain for each genotype were determined except GI.3. The GII.3 was the most major genotype following GI.1 and GIV.1. CONCLUSION: Our result confirmed that SaV is one of the pathogens detected from Taiwanese AGE patients. Multiple SaV genotype strains would associate with AGE as similar to those detected in different countries/areas. The whole genome of SaV strains detected including rarely reported GII.8 was firstly determined.


Subject(s)
Caliciviridae Infections , Gastroenteritis , Sapovirus , Caliciviridae Infections/epidemiology , Child , Child, Hospitalized , Disease Outbreaks , Feces , Gastroenteritis/epidemiology , Genotype , Humans , Phylogeny , Prospective Studies , Sapovirus/genetics , Taiwan/epidemiology
6.
Child Psychiatry Hum Dev ; 51(3): 355-365, 2020 06.
Article in English | MEDLINE | ID: mdl-31802296

ABSTRACT

Anxiety and depression are common emotional problems in children and adolescents. This study used a long-term tracking large database to investigate whether the proportion of children who were diagnosed with speech and language impairments were later diagnosed with anxiety or depression were significantly greater than that of matched group of the same age and gender without speech and language impairments. More than 4300 eligible children with speech and language impairments and matched controls were identified and assessed for anxiety and depression. The risk of anxiety and depressive disorders in children with speech and language impairments were examined with Cox regression analyses and adjusting for covariables (gender, age, and comorbidities). The results showed that speech and language impairments were positively associated with anxiety disorders (adjusted hazard ratio [AHR] 2.87, 95% confidence interval [CI] 2.20-3.76) and depressive disorders (AHR 2.51, 95% CI 1.52-4.13). The number of boys with speech and language impairments was more than twofold that of girls, but boys did not different from girls in the risk of anxiety disorders (AHR 0.95, 95% CI 0.75-1.20) and depressive disorders (AHR 0.72, 95% CI 0.47-1.11). Infantile autism and intellectual disabilities were positively associated with anxiety (AHR 1.54, 95% CI 1.07-2.21; AHR 1.47, 95% CI 1.09-1.98), and the latter was positively associated with depression (AHR 1.83, 95% CI 1.06-3.17). In addition to speech and language impairments interventions, our findings supported the necessity of identification and interventions in anxiety and depressive disorders among children with speech and language impairments from elementary school until youth.


Subject(s)
Anxiety Disorders/epidemiology , Depressive Disorder/epidemiology , Language Disorders/epidemiology , Adolescent , Child , Comorbidity , Female , Humans , Male , Schools , Speech Disorders/epidemiology , Taiwan/epidemiology
7.
Acta Neurol Taiwan ; 29(1): 18-23, 2020 Mar 30.
Article in English | MEDLINE | ID: mdl-32285430

ABSTRACT

BACKGROUND: Failure to recognize a carotid-cavernous fistula (CCF) promptly may lead to worse prognosis due to a setback in providing proper treatment. To promote early diagnosis of non-traumatic CCF, we report a case with classic clinical symptoms and signs that was diagnosed and followed up with carotid Doppler sonography (CDS) and transcranial color-coded duplex (TCD). CASE REPORT: A 45-year-old woman developed an intermittent headache, pulsatile tinnitus, and double vision sequentially within ten days. Progressive left retro-orbital pain, continuous ringing in the left ear, sensory impairment of trigeminal nerve and abducens nerve palsy were also noted on examination. Despite insignificant findings on computed tomography (CT) of the brain, TCD revealed an aberrant flow pattern with high velocity and low resistance at the left carotid siphon. Digital subtraction angiography (DSA) later confirmed a left direct type CCF by illustrating a quick opacification of left cavernous sinus via the internal carotid artery. CONCLUSION: In addition to invasive DSA, non-invasive CDS and TCD may serve as useful apparatus during the initial evaluation and subsequent follow-ups. The positive sonographic clues, including abnormal turbulent and hemodynamic parameters, are quite exhibitive in the existence of CCFs.


Subject(s)
Carotid-Cavernous Sinus Fistula , Embolization, Therapeutic , Angiography, Digital Subtraction , Carotid Artery, Internal , Female , Headache , Humans , Middle Aged , Tomography, X-Ray Computed
8.
Hum Mol Genet ; 26(12): 2247-2257, 2017 06 15.
Article in English | MEDLINE | ID: mdl-28369378

ABSTRACT

Myotonic dystrophy type 1 (DM1) is caused by an expansion of CTG repeats in the 3' untranslated region (UTR) of the dystrophia myotonia protein kinase (DMPK) gene. Cognitive impairment associated with structural change in the brain is prevalent in DM1. How this histopathological abnormality during disease progression develops remains elusive. Nuclear accumulation of mutant DMPK mRNA containing expanded CUG RNA disrupting the cytoplasmic and nuclear activities of muscleblind-like (MBNL) protein has been implicated in DM1 neural pathogenesis. The association between MBNL dysfunction and morphological changes has not been investigated. We generated a mouse model for postnatal expression of expanded CUG RNA in the brain that recapitulates the features of the DM1 brain, including the formation of nuclear RNA and MBNL foci, learning disability, brain atrophy and misregulated alternative splicing. Characterization of the pathological abnormalities by a time-course study revealed that hippocampus-related learning and synaptic potentiation were impaired before structural changes in the brain, followed by brain atrophy associated with progressive reduction of axon and dendrite integrity. Moreover, cytoplasmic MBNL1 distribution on dendrites decreased before dendrite degeneration, whereas reduced MBNL2 expression and altered MBNL-regulated alternative splicing was evident after degeneration. These results suggest that the expression of expanded CUG RNA in the DM1 brain results in neurodegenerative processes, with reduced cytoplasmic MBNL1 as an early event response to expanded CUG RNA.


Subject(s)
DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , 3' Untranslated Regions , Alternative Splicing , Animals , Brain/metabolism , Cell Nucleus/metabolism , Cytoplasm/metabolism , Disease Models, Animal , Exons , Humans , Mice , Myotonic Dystrophy/genetics , Myotonin-Protein Kinase/genetics , Myotonin-Protein Kinase/metabolism , RNA, Messenger/metabolism , Trinucleotide Repeat Expansion
9.
Eur Child Adolesc Psychiatry ; 27(3): 279-288, 2018 Mar.
Article in English | MEDLINE | ID: mdl-28856464

ABSTRACT

Preventive effect of stimulants on the risk of brain injuries had been reported. The aim of this study is to determine the extent to which methylphenidate (MPH) prescription moderates the risk of traumatic brain injuries (TBI) in individuals with attention-deficit/hyperactivity disorder (ADHD). Individuals with a recent diagnosis of ADHD between January 1997 and December 2013 (n = 163,618) were identified from Taiwan's National Health Insurance Research Database. A total of 124,438 adolescents and children with ADHD and without prior TBI diagnoses were included and evaluated for subsequent TBI. Methylphenidate prescription duration was subgrouped by the annual average cumulative defined daily dose (DDD): 0, >0 to ≤28, > 28 to ≤84, and >84. We identified 11,463 diagnoses of TBI among 124,438 adolescents and children with ADHD. A Cox regression model was used to investigate whether MPH prescription influenced the risk for TBI after adjusting for sex, age, level of urbanization, seizure, autism and sedative-anxiolytics use. A reduced TBI incidence was observed with MPH prescription DDDs > 84. The protective effect of MPH against TBI persisted after adjusting for confounding factors [hazard ratio (HR) = 0.49; 95% confidence interval (CI): 0.47-0.51]. There was also statistically significant difference in risk for TBI in subjects receiving > 0 to ≤28 or >28 to ≤84 DDDs of MPH treatment (HR = 0.88, 95% CI = 0.83-0.92; HR = 0.76, 95% CI = 0.72-0.80, respectively) when compared with subjects not receiving treatment with MPH. Treatment with MPH for greater than 84 DDDs reduced the risk for TBI among children with ADHD.


Subject(s)
Attention Deficit Disorder with Hyperactivity/drug therapy , Brain Injuries, Traumatic/drug therapy , Central Nervous System Stimulants/therapeutic use , Methylphenidate/therapeutic use , Adolescent , Attention Deficit Disorder with Hyperactivity/complications , Central Nervous System Stimulants/pharmacology , Child , Child, Preschool , Drug Dosage Calculations , Female , Humans , Infant , Infant, Newborn , Male , Methylphenidate/pharmacology , Risk , Taiwan/epidemiology
10.
Emerg Infect Dis ; 23(7): 1180-1183, 2017 07.
Article in English | MEDLINE | ID: mdl-28585917

ABSTRACT

In Taiwan, acute gastroenteritis outbreaks caused by a new norovirus genotype GII.2 increased sharply toward the end of 2016. Unlike previous outbreaks, which often involved restaurants, GII.2 outbreaks mainly occurred in schools. Phylogenetic analysis indicates that these noroviruses are recombinant GII.P16-GII.2 strains.


Subject(s)
Caliciviridae Infections/epidemiology , Caliciviridae Infections/virology , Genome, Viral , Norovirus/genetics , Recombination, Genetic , Caliciviridae Infections/history , Disease Outbreaks , Gastroenteritis/epidemiology , Gastroenteritis/history , Gastroenteritis/virology , Genotype , History, 21st Century , Humans , Norovirus/classification , Open Reading Frames , Phylogeny , RNA, Viral , Seasons , Sequence Analysis, DNA , Taiwan/epidemiology
11.
Biol Proced Online ; 19: 12, 2017.
Article in English | MEDLINE | ID: mdl-28959142

ABSTRACT

Site-directed mutagenesis (SDM) has been widely used for studying the structure and function of proteins. A one-step polymerase chain reaction (PCR)-based multiple site-directed plasmid mutagenesis method with extended non-overlapping sequence at the 3' end of the primer increases the PCR amplification efficiency and the capacity of multi-site mutagenesis. Here, we introduced silent restriction sites in the primers used in this PCR-based SDM method by utilizing SDM-Assist software to generate mutants of Helicobacter pylori neutrophil-activating protein (HP-NAP), whose gene has low GC content. The HP-NAP mutants were efficiently generated by this modified mutagenesis method and quickly identified by a simple restriction digest due to the presence of the silent restriction site. This modified PCR-based SDM method with the introduction of a silent restriction site on the primer is efficient for generation and identification of mutations in the gene of interest.

12.
BMC Biotechnol ; 15: 23, 2015 Apr 08.
Article in English | MEDLINE | ID: mdl-25880121

ABSTRACT

BACKGROUND: Helicobacter pylori neutrophil-activating protein (HP-NAP) is involved in H. pylori-induced gastric inflammation. Due to its immunogenic and immunomodulatory properties, HP-NAP has been used for developing vaccines against H. pylori infection and new drugs for cancer therapy. RESULTS: Here, we provide a simple process for high-yield production of HP-NAP by applying one-step negative chromatography to purify recombinant HP-NAP expressed in Escherichia coli (E. coli). In our E. coli expression system, recombinant HP-NAP constitutes nearly 70% of the total protein. Overexpressed recombinant HP-NAP is almost completely soluble upon cell lysis at pH 9.5. Under the optimal condition at pH 8.0, recombinant HP-NAP with purity higher than 95% can be obtained from E. coli by collecting the unbound fraction using diethylaminoethyl (DEAE) Sephadex resin in batch mode. The overall yield of HP-NAP from a 50-ml E. coli culture is ~19 mg. The purified HP-NAP folds into a multimer with a secondary structure of α-helix and is able to trigger the production of reactive oxygen species by neutrophils. CONCLUSIONS: Purification of recombinant HP-NAP overexpressed in E. coli using DEAE Sephadex negative mode batch chromatography is an efficient method for high-yield production of highly pure HP-NAP in its native state. The purified HP-NAP is useful for various clinical applications including vaccine development, diagnosis, and new drug development.


Subject(s)
Bacterial Proteins/isolation & purification , Bacterial Proteins/metabolism , Escherichia coli/genetics , Helicobacter pylori/genetics , Recombinant Proteins/isolation & purification , Recombinant Proteins/metabolism , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Chromatography , Helicobacter pylori/chemistry , Hydrogen-Ion Concentration , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Solubility
13.
J Diabetes Investig ; 15(2): 227-236, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37882416

ABSTRACT

AIMS/INTRODUCTION: Delayed intensification of treatment, or therapeutic inertia, increases the risk of diabetic complications and death. The aim of this study was to determine the effect of mandatory monthly outpatient visits on therapeutic inertia in patients with suboptimal control of type 2 diabetes. MATERIALS AND METHODS: This retrospective cohort study used data from the Chang Gung Research Database and defined two study periods: the baseline period and the intervention period. The intervention period began when the Kaohsiung branch initiated a mandatory monthly outpatient visits program. Type 2 diabetes patients with baseline glycated hemoglobin (HbA1c) >7% and a follow-up HbA1c measurement were enrolled in each period, and divided into a Kaohsiung branch (intervention) group and the other branches (control) group. Therapy intensification was evaluated by comparing prescriptions after the follow-up HbA1c measurement with the prescriptions after the baseline HbA1c measurement. RESULTS: A total of 5,045 patients at the Kaohsiung branch and 13,400 participants at other branches were enrolled in the baseline period; and 5,573 and 15,603 patients, respectively, were enrolled in the intervention period. The adjusted odds ratio (AOR) for therapy intensification in patients with baseline HbA1c ≥9% was not significantly higher at 1.21 (95% CI, 1.00-1.47) in the intervention period at the Kaohsiung branch, but was significantly higher (AOR, 1.53; 95% CI, 1.02-2.30) in the subgroup with worsened HbA1c. CONCLUSIONS: Mandatory monthly outpatient visits could improve therapeutic inertia in patients with poorly controlled type 2 diabetes, especially in those with worsened control. The trajectory of HbA1c could significantly influence the assessment of the prevalence of therapeutic inertia.


Subject(s)
Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Hypoglycemic Agents/therapeutic use , Glycated Hemoglobin , Retrospective Studies , Outpatients
14.
ACS Biomater Sci Eng ; 10(5): 3306-3315, 2024 05 13.
Article in English | MEDLINE | ID: mdl-38634810

ABSTRACT

Tissue engineering primarily aimed to alleviate the insufficiency of organ donations worldwide. Nonetheless, the survival of the engineered tissue is often compromised due to the complexity of the natural organ architectures, especially the vascular system inside the organ, which allows food-waste transfer. Thus, vascularization within the engineered tissue is of paramount importance. A critical aspect of this endeavor is the ability to replicate the intricacies of the extracellular matrix and promote the formation of functional vascular networks within engineered constructs. In this study, human adipose-derived stem cells (hADSCs) and human umbilical vein endothelial cells (HUVECs) were cocultured in different types of gelatin methacrylate (GelMA). In brief, pro-angiogenic signaling growth factors (GFs), vascular endothelial growth factor (VEGF165) and basic fibroblast growth factor (bFGF), were conjugated onto GelMA via an EDC/NHS coupling reaction. The GelMA hydrogels conjugated with VEGF165 (GelMA@VEGF165) and bFGF (GelMA@bFGF) showed marginal changes in the chemical and physical characteristics of the GelMA hydrogels. Moreover, the conjugation of these growth factors demonstrated improved cell viability and cell proliferation within the hydrogel construct. Additionally, vascular-like network formation was observed predominantly on GelMA@GrowthFactor (GelMA@GF) hydrogels, particularly on GelMA@bFGF. This study suggests that growth factor-conjugated GelMA hydrogels would be a promising biomaterial for 3D vascular tissue engineering.


Subject(s)
Coculture Techniques , Fibroblast Growth Factor 2 , Human Umbilical Vein Endothelial Cells , Hydrogels , Tissue Engineering , Humans , Adipose Tissue/cytology , Cell Proliferation/drug effects , Cell Survival/drug effects , Fibroblast Growth Factor 2/pharmacology , Fibroblast Growth Factor 2/metabolism , Gelatin/chemistry , Gelatin/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Intercellular Signaling Peptides and Proteins/pharmacology , Intercellular Signaling Peptides and Proteins/metabolism , Methacrylates/chemistry , Methacrylates/pharmacology , Neovascularization, Physiologic/drug effects , Stem Cells/cytology , Stem Cells/metabolism , Stem Cells/drug effects , Tissue Engineering/methods , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/pharmacology
15.
Neuropsychiatr Dis Treat ; 20: 247-255, 2024.
Article in English | MEDLINE | ID: mdl-38348059

ABSTRACT

Purpose: Autism spectrum disorder (ASD) may be associated with increased mortality, but relevant findings have been inconsistent. The modifying effects of gender and intellectual disability on excess mortality in individuals with ASD are underexplored. Patients and Methods: Using Taiwan's National Health Insurance Research Database and the National Death Registry, this population-based cohort study selected the data of 75,946 patients with ASD (ASD cohort) and 75,946 age group-, gender-, and income-matched (1:1) patients without ASD (non-ASD cohort). Cox proportional hazards models were used to compare mortality rates between the cohorts, and stratified analyses were used to evaluate the influence of gender and intellectual disability on mortality risk. Results: The ASD cohort had higher mortality rates for all causes of death than did the non-ASD cohort (adjusted hazard ratio 1.64, 95% confidence interval 1.54-1.75). Comorbid intellectual disability was associated with an increased risk of mortality, and this association was stronger in female patients than in male patients. Moreover, when focusing on deaths from natural causes, we found a significantly higher odds ratio for mortality in the ASD population with ID compared to those without ID. Conclusion: ASD is associated with increased mortality, especially among female individuals and those with intellectual disability.

16.
Acta Neuropathol Commun ; 11(1): 44, 2023 03 15.
Article in English | MEDLINE | ID: mdl-36922901

ABSTRACT

Reduced brain volume including atrophy in grey and white matter is commonly seen in myotonic dystrophy type 1 (DM1). DM1 is caused by an expansion of CTG trinucleotide repeats in the 3' untranslated region (UTR) of the Dystrophia Myotonica Protein Kinase (DMPK) gene. Mutant DMPK mRNA containing expanded CUG RNA (DMPK-CUGexp) sequesters cytoplasmic MBNL1, resulting in morphological impairment. How DMPK-CUGexp and loss of MBNL1 cause histopathological phenotypes in the DM1 brain remains elusive. Here, we show that BDNF-TrkB retrograde transport is impaired in neurons expressing DMPK-CUGexp due to loss of cytoplasmic MBNL1 function. We reveal that mature BDNF protein levels are reduced in the brain of the DM1 mouse model EpA960/CaMKII-Cre. Exogenous BDNF treatment did not rescue impaired neurite outgrowth in neurons expressing DMPK-CUGexp, whereas overexpression of the cytoplasmic MBNL1 isoform in DMPK-CUGexp-expressing neurons improved their responsiveness to exogenous BDNF. We identify dynein light chain LC8-type 2, DYNLL2, as an MBNL1-interacting protein and demonstrate that their interaction is RNA-independent. Using time-lapse imaging, we show that overexpressed MBNL1 and DYNLL2 move along axonal processes together and that MBNL1-knockdown impairs the motility of mCherry-tagged DYNLL2, resulting in a reduced percentage of retrograde DYNLL2 movement. Examination of the distribution of DYNLL2 and activated phospho-TrkB (pTrkB) receptor in EpA960/CaMKII-Cre brains revealed an increase in the postsynaptic membrane fraction (LP1), indicating impaired retrograde transport. Finally, our neuropathological analysis of postmortem DM1 tissue reveals that reduced cytoplasmic MBNL1 expression is associated with an increase in DYNLL2 and activated pTrkB receptor levels in the synaptosomal fraction. Together, our results support that impaired MBNL1-mediated retrograde BDNF-TrkB signaling may contribute to the histopathological phenotypes of DM1.


Subject(s)
Myotonic Dystrophy , Animals , Mice , Myotonic Dystrophy/genetics , Myotonic Dystrophy/metabolism , Myotonic Dystrophy/pathology , Brain-Derived Neurotrophic Factor/metabolism , Trinucleotide Repeat Expansion , Myotonin-Protein Kinase/genetics , Myotonin-Protein Kinase/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics , RNA/genetics , Brain/pathology , DNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism
17.
Medicine (Baltimore) ; 102(26): e34128, 2023 Jun 30.
Article in English | MEDLINE | ID: mdl-37390292

ABSTRACT

The coronavirus disease 2019 has become a threat to global healthcare because of its rapid spread and evolution. In severe cases, the initial management of the disease is mainly supportive therapy and mechanical ventilation. Therefore, we investigated whether a modified emergency department workflow affects the efficacy will influence the efficacy and patient outcomes of traumatic brain injury (TBI) in Taiwan. This retrospective observational study used the Chang Gung Research Database in Taiwan from 7 hospitals in the Chang Gung Memorial Hospital System. Clinical index parameters and treatment efficiencies were analyzed between the locally transmitted period (January 20, 2020-June 7, 2020, period 2) and the community spread period (May 19, 2021-July 27, 2021, period 4) with the same interval of the pre-pandemic in 2019 as a reference period. During the locally transmitted period, only the time interval for patients who had to wait for a brain CT examination was, on average, 7.7 minutes shorter, which reached statistical significance. In addition, the number of TBI patients under 18 years of age decreased significantly during the community spread period. The "Door to the operating room (OR)," with polymerase chain reaction (PCR) testing, was on average 109.7 minutes slower than without the PCR testing in the reference period 2019. TBI treatment efficiency was delayed because of the PCR test. However, the surgical volume and functional outcome during these 2 periods were statistically insignificant compared to the pre-pandemic period because the spread of the virus was well controlled and hospital capacity was increased.


Subject(s)
Brain Injuries, Traumatic , COVID-19 , Humans , Adolescent , COVID-19/epidemiology , Taiwan/epidemiology , Pandemics , Brain Injuries, Traumatic/epidemiology , Brain Injuries, Traumatic/therapy , Databases, Factual
18.
Nanomaterials (Basel) ; 13(9)2023 May 08.
Article in English | MEDLINE | ID: mdl-37177120

ABSTRACT

In this study, thermal and argon (Ar) plasma/wetting treatments were combined to enhance the bonding strength of polyimide (PI) films. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) was used to analyze the changes in the PI imidization degrees. The contact angles of the PI films were also measured. The results show that the contact angles of the fully cured PI films markedly decreased from 78.54° to 26.05° after the Ar plasma treatments. X-ray photoelectron spectroscopy (XPS) analysis was also conducted on the PI surfaces. We found that the intensities of the C-OH and C-N-H bonds increased from 0% to 13% and 29% to 57%, respectively, after Ar plasma activation. Such increases in the C-OH and C-N-H intensities could be attributed to the generation of dangling bonds and the breakage of the imide ring or polymer long chains. Shear tests were also conducted to characterize the bonding strength of the PI films, which, after being treated with the appropriate parameters of temperature, plasma power, and wetting droplets, was found to be excellent at greater than 35.3 MPa.

19.
Eur Heart J Cardiovasc Pharmacother ; 9(6): 507-514, 2023 09 20.
Article in English | MEDLINE | ID: mdl-37170917

ABSTRACT

BACKGROUND: Chronic hepatitis C virus (HCV) infection is associated with increased cardiovascular risks. We aimed to investigate the impact of direct acting antiviral (DAA) on HCV-associated cardiovascular events. METHODS: In this retrospective cohort study, patients with the diagnosis of chronic HCV were retrieved from multi-institutional electronic medical records, where diagnosis of HCV was based on serum HCV antibody and HCV-RNA test. The patients eligible for analysis were then separated into patients with DAA treatment and patient without DAA treatment. Primary outcomes included acute coronary syndrome, heart failure (HF), venous thromboembolism (VTE), stroke, cardiovascular death, major adverse cardiovascular event (MACE), and all-cause mortality. Outcomes developed during follow-up were compared between DAA treatment and non-DAA treatment groups. RESULTS: There were 41 565 patients with chronic HCV infection identified. After exclusion criteria applied, 1984 patients in the DAA treatment group and 413 patients in the non-DAA treatment group were compared for outcomes using inverse probability of treatment weighting. Compared to patients in non-DAA treatment group, patients in DAA treatment group were associated with significantly decreased HF (hazard ratio [HR]: 0.65, 95% confidence interval [CI]: 0.44-0.97, P = 0.035), VTE (HR: 0.19, 95% CI: 0.07-0.49, P = 0.001), MACE (HR: 0.73, 95% CI 0.59-0.92, P = 0.007), and all-cause mortality (HR: 0.50, 95% CI: 0.38-0.67, P < 0.001) at 3-year follow-up. CONCLUSIONS: Chronic HCV patients treated with DAA experienced lower rates of cardiovascular events and all-cause mortality than those without treatment. The reduction of VTE was the most significant impact of DAA treatment among the cardiovascular outcomes.


Subject(s)
Heart Failure , Hepatitis C, Chronic , Hepatitis C , Venous Thromboembolism , Humans , Antiviral Agents/adverse effects , Hepacivirus/genetics , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/drug therapy , Retrospective Studies , Venous Thromboembolism/diagnosis , Venous Thromboembolism/epidemiology , Hepatitis C/complications , Hepatitis C/drug therapy , Heart Failure/diagnosis , Heart Failure/drug therapy
20.
Infect Genet Evol ; 98: 105198, 2022 03.
Article in English | MEDLINE | ID: mdl-34968762

ABSTRACT

BACKGROUND: Rotavirus A (RVA) are a group of diverse viruses causing acute gastroenteritis (AGE) in humans and animals. Zoonotic transmission is an important mechanism for rotavirus evolution and strain diversity in humans, but the extent of pigs as a major reservoir for human infection is not clear. METHODS AND FINDINGS: We have surveyed 153 pig farms across Taiwan with a total of 4588 porcine stool samples from three age groups from 2014 to 2017. Nursing piglets (less than one month of age) had higher detection rate for rotavirus than older age groups. Five VP7 (G) genotypes and 5 VP4 (P) genotypes were found in a total of 14 different G/P genotype combinations. In addition, porcine RVA strains had 2 NSP4 (E) genotypes and 3 VP6 (I) genotypes. A P[3]-like genotype was also discovered among strains collected in 2016 and 2017. CONCLUSIONS: Most of the genes from Taiwanese porcine strains clustered with each other and the lineages formed by these strains were distinct from the sequences of numerous regional variants or globally circulating porcine strains, suggesting an independent evolutionary history for Taiwanese rotavirus genotypes. The close relationship among porcine RVA strains and some unique porcine-like genotypes detected sporadically among human children in swine farms illustrates that pigs might serve as a reservoir for potential zoonotic transmission and novel genotype evolution in Taiwan's insular environment.


Subject(s)
Disease Reservoirs/veterinary , Genetic Variation , Rotavirus Infections/veterinary , Rotavirus/physiology , Swine Diseases/epidemiology , Animals , Feces/virology , Humans , Prevalence , Rotavirus/genetics , Rotavirus Infections/epidemiology , Sus scrofa , Swine , Taiwan/epidemiology
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