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1.  Higher Daily Physical Activities Continue to Preserve Muscle Strength After Mid-Life, But Not Muscle Mass After Age of 75 
Medicine  2016;95(22):e3809.
The objective of this study is to explore the impact of aging and daily physical activities (PA) on muscle mass and muscle strength among community-dwelling people in Taiwan.
The design is a cross-sectional study. Setting is a population-based community study.
One thousand eight hundred thirty-nine community-dwelling people aged 50 years and older in Taiwan participated in the study.
Measurements include demographic characteristics, Charlson Comorbidity Index (CCI) for multimorbidity, mini-nutritional assessment (MNA) for nutritional evaluation, functional autonomy measurement system (SMAF) for functional capacity, Chinese version mini mental state examination (MMSE), 5-item Taiwan Geriatric Depression Scale (TGDS-5), Chinese version of International Physical Activity Questionnaire (IPAQ), height-adjusted skeletal muscle index (SMI) by dual-energy X-ray absorptiometry, handgrip strength, timed 6-m walking test for usual gait speed. Laboratory measurements include testosterone, sex-hormone binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEA-S), insulin-like growth factor-1 (IGF-1), high-sensitivity C-reactive protein (hsCRP), 25-OH vitamin D, and insulin resistance.
After adjusted for age, the lowest PA tertile was associated with multimorbidity, poorer functional capacity and nutritional status, more depressive symptoms, lower SMI and lower handgrip strength, and lower free androgen index (FAI) in men. The negative association between PA and low SMI was more significant among subjects aged younger than 65 and the association decreased with older age. For subjects aged younger than 65, moderate daily PA (Q2) group had lower risk of low SMI compared with Q1 participants (OR: 0.62, 95% CI = 0.39–0.98, P = 0.040). For muscle strength, higher daily PA was associated with lower risk of low handgrip strength after age of 65 and the effect was dose-dependent. The effect was attenuated by potential confounders during age 65 to 74, while after age 75, the result was almost unchanged in fully adjusted model (OR = 0.37, 95% CI = 0.18–0.79, P = 0.010).
Older age may attenuate the protective effects of higher daily PA on preventing muscle loss, but higher daily PA continues to preserve muscle strength at different age groups, even after the age of 75. The prognostic role of daily PA may be mediated by muscle strength instead of muscle mass among people aged 75 years and older.
PMCID: PMC4900727  PMID: 27258519
2.  Primary Sjögren's syndrome initially presenting as submandibular mucosa-associated lymphoid tissue lymphoma: A case report 
Oncology Letters  2015;11(2):921-924.
The present study reports the case of a 24-year-old female affected with primary Sjögren's syndrome (pSS), who presented with mucosa-associated lymphoid tissue (MALT) lymphoma of the submandibular gland. Reports of such cases, particularly in young patients, are very rare. The patient, who presented no oral or ocular symptoms prior to the development of the mass, underwent surgical ablation of the gland, and MALT lymphoma was diagnosed by histopathology. Since MALT lymphoma in the submandibular gland is rarely observed in otherwise healthy young females, a rheumatologist and an oncologist were consulted. Following a number of immunological tests, the results of the Schirmer's and Saxon tests were negative. However, the antinuclear antibody test revealed a speckled appearance, and there was also strong positivity for the serological markers of Sjögren's syndrome. Consequently, pSS was diagnosed, despite the fact that the patient did not fulfill all the diagnostic criteria for the disease. Therefore, MALT lymphoma in a single salivary gland should be used as a differential diagnosis for Sjögren's syndrome in young asymptomatic patients. Additionally, a multidisciplinary team is required for the treatment and management of these patients.
PMCID: PMC4734050  PMID: 26893669
Sjögren's syndrome; mucosa associated lymphoid tissue lymphoma; submandibular swelling
3.  Association between Frailty, Osteoporosis, Falls and Hip Fractures among Community-Dwelling People Aged 50 Years and Older in Taiwan: Results from I-Lan Longitudinal Aging Study 
PLoS ONE  2015;10(9):e0136968.
Association of frailty with adverse clinical outcomes has been reported in Western countries, but data from the Asian population are scarce. This study aimed to evaluate the epidemiology of frailty among community-dwelling middle-aged and elderly population and to explore its association with musculoskeletal health in Taiwan.
I-Lan Longitudinal Aging Study (ILAS) data were retrieved for this study. Frailty was defined by the Fried’s criteria; a comparison of demographic characteristics, physical performance, and body composition, including skeletal muscle mass and bone mineral density (BMD), as well as recent falls, history of hip fractures and the functional status of subjects with different frailty statuses were accomplished.
Overall, the data of 1,839 participants (mean age: 63.9±9.3 years, male 47.5%) were obtained for analysis. The prevalence of pre-frailty was 42.3% in men and 38.8% in women, whereas the prevalence of frailty was 6.9% and 6.7% in men and women, respectively. Frailty was significantly associated with older age, the male gender, larger waist circumference, lower skeletal muscle index, lower hip BMD, poorer physical function, poorer nutritional status, and poorer cognitive function. Also, frailty was significantly associated with osteoporosis (OR: 7.73, 95% CI: 5.01–11.90, p<0.001), history of hip fractures (OR: 8.66, 95% CI: 2.47–30.40, p = 0.001), and recent falls (O.R: 2.53, 95% CI: 1.35–4.76, p = 0.004).
Frailty and pre-frailty, in Taiwan, was closely associated with recent falls, history of hip fractures and osteoporosis among community-dwelling people 50 years of age and older. Furthermore, frailty intervention programs should take an integrated approach towards strengthening both and muscle mass, as well as prevention of falls.
PMCID: PMC4562637  PMID: 26348034
4.  MiR-34a regulates blood–tumor barrier function by targeting protein kinase Cε 
Molecular Biology of the Cell  2015;26(10):1786-1796.
It is shown for the first time that overexpression of miR-34a increases blood–tumor barrier permeability by targeting PKCε, which is activated by p-PKCε and directly regulates the expression of tight junction–related proteins.
MicroRNA-34a (miR-34a) functions to regulate protein expression at the posttranscriptional level by binding the 3′ UTR of target genes and regulates functions of vascular endothelial cells. However, the role of miR-34a in regulating blood–tumor barrier (BTB) permeability remains unknown. In this study, we show that miR-34a overexpression leads to significantly increased permeability of BTB, whereas miR-34a silencing reduces the permeability of the BTB. In addition, miR-34a overexpression significantly down-regulates the expression and distribution of tight junction–related proteins in glioma endothelial cells (GECs), paralleled by protein kinase Cε (PKCε) reduction. Moreover, luciferase reporter gene analysis shows that PKCε is the target gene of miR-34a. We also show that cotransfection of miR-34a and PKCε inversely coregulates BTB permeability and protein expression levels of tight junction–related proteins. Pretreatment of ψεRACK, a PKCε-specific activator, decreases BTB permeability in miR-34a–overexpressed GECs and up-regulates expression levels of tight junction proteins. In contrast, pretreatment of εV1-2, a specific PKCε inhibitor, gives opposite results. Collectively, our findings indicate that miR-34a regulates BTB function by targeting PKCε; after phosphorylation, PKCε is activated and contributes to regulation of the expression of tight junction–related proteins, ultimately altering BTB permeability.
PMCID: PMC4436826  PMID: 25788289
5.  The anti-aging effects of Ludwigia octovalvis on Drosophila melanogaster and SAMP8 mice 
Age  2013;36(2):689-703.
We investigated the anti-aging effects of Ludwigia octovalvis (Jacq.) P. H. Raven (Onagraceae), an extract of which is widely consumed as a healthful drink in a number of countries. Using the fruit fly, Drosophila melanogaster, as a model organism, we demonstrated that L. octovalvis extract (LOE) significantly extended fly lifespan on a high, but not a low, calorie diet, indicating that LOE may regulate lifespan through a dietary restriction (DR)-related pathway. LOE also attenuated age-related cognitive decline in both flies and in the senescence-accelerated-prone 8 (SAMP8) mouse, without causing any discernable negative trade-offs, including water intake, food intake, fecundity, or spontaneous motor activity. LOE contained high levels of polyphenols and flavonoids, which possess strong DPPH radical scavenging activity, and was shown to attenuate paraquat-induced oxidative damage and lethality in flies. Gas chromatography–mass spectrometry (GC-MS) analyses identified 17 known molecules, of which β-sitosterol and squalene were the two most abundant. We further demonstrated that β-sitosterol was capable of extending lifespan, likely through activating AMP-activated protein kinase (AMPK) in the fat body of adult flies. Taken together, our data suggest that LOE is a potent anti-aging intervention with potential for treating age-related disorders.
Electronic supplementary material
The online version of this article (doi:10.1007/s11357-013-9606-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4039272  PMID: 24338263
Ludwigia octovalvis; Dietary restriction; Lifespan; AMPK
6.  Location, Location, Location: How Does a Spermatogonium Know It Is a Spermatogonial Stem Cell (SSC)?1 
Biology of Reproduction  2013;88(5):132.
In this issue of Biology of Reproduction, de Rooij and van Beek describe a computer model simulating the population dynamics and interactions of SSCs and their descendants in and around the spermatogonial niche.
PMCID: PMC4013916  PMID: 23616590
7.  A risk factor analysis of healthcare-associated fungal infections in an intensive care unit: a retrospective cohort study 
The incidence of fungal healthcare-associated infection (HAI) has increased in a major teaching hospital in the northern part of Taiwan over the past decade, especially in the intensive care units (ICUs). The purpose of this study was to determine the factors that were responsible for the outbreak and trend in the ICU.
Surveillance fungal cultures were obtained from “sterile” objects, antiseptic solutions, environment of infected patients and hands of medical personnel. Risk factors for comparison included age, gender, admission service, and total length of stay in the ICU, Acute Physiology and Chronic Health Evaluation (APACHE) II scores at admission to the ICU, main diagnosis on ICU admission, use of invasive devices, receipt of hemodialysis, total parenteral nutrition (TPN) use, history of antibiotic therapy before HAI or during ICU stay in no HAI group, and ICU discharge status (ie, dead or alive). Univariable analysis followed by multiple logistic regression analysis was performed to identify the independent risk factors for ICU fungal HAIs and ICU mortality.
There was a significant trend in ICU fungal HAIs from 1998 to 2009 (P < 0.001). A total of 516 episodes of ICU fungal HAIs were identified; the rates of various infections were urinary tract infection (UTI) (54.8%), blood stream infection (BSI) (30.6%), surgical site infection (SSI) (6.6%), pneumonia (4.5%), other sites (3.5%). The fungi identified were: yeasts (54.8%), Candida albicans (27.3%), Candida tropicalis (6.6%), Candida glabrata (6.6%), Candida parapsilosis (1.9%), Candida species (0.8%), and other fungi (1.9%). Candida albicans accounted for 63% of all Candida species. Yeasts were found in the environment of more heavily infected patients. The independent risk factors (P < 0.05) of developing ICU fungal HAIs from all sites were TPN use, sepsis, surgical patients, mechanical ventilation and an indwelling urinary catheter. The independent risk factors for ICU fungal UTI included TPN use, mechanical ventilation and an indwelling urinary catheter. The independent risk factors for ICU fungal BSI included TPN use, sepsis, and higher APACHE II score. The independent risk factors for ICU fungal pneumonia included TPN use, surgical patients. The independent risk factors for ICU fungal SSI included surgical patients, and TPN use. The odds ratios of TPN use in various infection types ranged from 3.51 to 8.82. The risk of mortality in patients with ICU fungal HAIs was over 2 times that of patients without ICU HAIs in the multiple logistic regression analysis (P < 0.001).
There was a secular trend of an increasing number of fungal HAIs in our ICU over the past decade. Patients with ICU fungal HAIs had a significantly higher mortality rate than did patients without ICU HAIs. Total parenteral nutrition was a significant risk factor for all types of ICU fungal HAIs, and its use should be monitored closely.
PMCID: PMC3548709  PMID: 23298156
Intensive care unit; Fungal infection; Outbreak surveillance; Candida; Total parenteral nutrition
8.  Surveillance on secular trends of incidence and mortality for device–associated infection in the intensive care unit setting at a tertiary medical center in Taiwan, 2000–2008: A retrospective observational study 
BMC Infectious Diseases  2012;12:209.
Device–associated infection (DAI) plays an important part in nosocomial infection. Active surveillance and infection control are needed to disclose the specific situation in each hospital and to cope with this problem effectively. We examined the rates of DAI by antimicrobial-resistant pathogens, and 30–day and in–hospital mortality in the intensive care unit (ICU).
Prospective surveillance was conducted in a mixed medical and surgical ICU at a major teaching hospital from 2000 through 2008. Trend analysis was performed and logistic regression was used to assess prognostic factors of mortality.
The overall rate of DAIs was 3.03 episodes per 1000 device–days. The most common DAI type was catheter–associated urinary tract infection (3.76 per 1000 urinary catheter–days). There was a decrease in DAI rates in 2005 and rates of ventilator–associated pneumonia (VAP, 3.18 per 1000 ventilator–days) have remained low since then (p < 0.001). The crude rates of 30–day (33.6%) and in–hospital (52.3%) mortality, as well as infection by antibiotic-resistant VAP pathogens also decreased. The most common antimicrobial-resistant pathogens were methicillin–resistant Staphylococcus aureus (94.9%) and imipenem–resistant Acinetobacter baumannii (p < 0.001), which also increased at the most rapid rate. The rate of antimicrobial resistance among Enterobacteriaceae also increased significantly (p < 0.05). After controlling for potentially confounding factors, the DAI was an independent prognostic factor for both 30–day mortality (OR 2.51, 95% confidence interval [CI] 1.99–3.17, p = 0.001) and in–hospital mortality (OR 3.61, 95% CI 2.10–3.25, p < 0.001).
The decrease in the rate of DAI and infection by resistant bacteria on the impact of severe acute respiratory syndrome can be attributed to active infection control and improved adherence after 2003.
PMCID: PMC3458996  PMID: 22963041
Surveillance; Secular trend; Device–associated infection; Intensive care unit; Infection control
9.  High-dose daptomycin and fosfomycin treatment of a patient with endocarditis caused by daptomycin-nonsusceptible Staphylococcus aureus: Case report 
BMC Infectious Diseases  2011;11:152.
Emergence of daptomycin-nonsusceptible (DNS) Staphylococcus aureus is a dreadful problem in the treatment of endocarditis. Few current therapeutic agents are effective for treating infections caused by DNS S. aureus.
Case presentation
We describe the emergence of DNS S. aureus. in a patient with implantable cardioverter-defibrillator (ICD) device -related endocarditis who was priorily treated with daptomycin. Metastatic dissemination as osteomyelitis further complicated the management of endocarditis. The dilemma was successfully managed by surgical removal of the ICD device and combination antimicrobial therapy with high-dose daptomycin and fosfomycin.
Surgical removal of intracardiac devices remains an important adjunctive measure in the treatment of endocarditis. Our case suggests that combination therapy is more favorable than single-agent therapy for infections caused by DNS S. aureus.
PMCID: PMC3119071  PMID: 21612672
Daptomycin-nonsusceptible; fosfomycin; ICD device-related endocarditis
10.  2-[(1,3-Benzothia­zol-2-yl)imino­meth­yl]phenol 
The title compound, C14H10N2OS, is nearly planar, with a maximum deviation of 0.0698 (13) Å from the mean plane, and exists in an E configuration with respect to the C=N bond. The dihedral angle between the two benzene rings is 2.81 (9)°. There is an intra­molecular O—H⋯N hydrogen bond and inter­molecular C—H⋯O and C—H⋯N hydrogen bonds.
PMCID: PMC2968841  PMID: 21582471

Results 1-10 (10)