A Nonlinear Association between Neighborhood Walkability and Risks of Sarcopenia in Older Adults.

OBJECTIVES: Neighborhood walkability has been found to be positively related to physical activity and negatively associated with risks of noncommunicable diseases. However, limited studies have examined its association with sarcopenia in older adults. Thus, this study aimed to examine the association between neighborhood walk score and risks of sarcopenia in a sample of older Taiwanese adults. DESIGN AND SETTING: This study was a cross-sectional investigation using telephone-based survey. PARTICIPANTS: A nationwide telephone-based survey targeting older adults (≥ 65 years) was conducted in Taiwan. MEASUREMENTS: Data on neighborhood walkability (determined by walk score of residential neighborhood), sarcopenia scores (measured by SARC-F), and personal characteristics were obtained. The relationships between walk score and risks of sarcopenia were examined using generalized additive models. RESULTS: A total of 1,056 older adults participated in the survey. In model 1 (sex and age) and model 2 (full-adjusted model), a nonlinear association between neighborhood walk score and risks of sarcopenia was observed. Results showed that risks of sarcopenia appear to be lower in neighborhoods with a 40-walk score (Car-Dependent; most errands require a car) and an 80-walk score (Very Walkable) and highest in the neighborhood with a 60-walk score (Somewhat Walkable). CONCLUSIONS: The study revealed a nonlinear relationship between neighborhood walkability and risks of sarcopenia in older adults in Asian context. Results provided information to urban designers and public health practitioners that more walkable neighborhood may not necessarily protect older adults from risks of sarcopenia.

Variation assessment of deformable registration in stereotactic radiosurgery.

INTRODUCTION: The regular functions of CT-MRI registration include delineation of targets and organs-at-risk (OARs) in radiosurgery planning. The question of whether deformable image registration (DIR) could be applied to stereotactic radiosurgery (SRS) in its place remains a subject of debate. METHODS: This study collected data regarding 16 patients who had undergone single-fraction SRS treatment. All lesions were located close to the brainstem. CT and MRI two image sets were registered by both rigid image registration (RIR) and DIR algorithms. The contours of the OARs were drawn individually on the rigid and deformable CT-MRI image sets by qualified radiation oncologists and dosimetrists. The evaluation metrics included volume overlapping (VO), Dice similarity coefficient (DSC), and dose. The modified demons deformable algorithm (VARIAN SmartAdapt) was used for evaluation in this study. RESULTS: The mean range of VO for OARs was 0.84 ± 0.08, and DSC was 0.82 ± 0.07. The maximum average volume difference was at normal brain (17.18 ± 14.48 cm3) and the second highest was at brainstem (2.26 cm3 ± 1.18). Pearson correlation testing showed that all DIRs' OAR volumes were linearly and significantly correlated with RIRs' volume (0.679-0.992, two tailed, P << 0.001). The 100% dose was prescribed at gross tumor volume (GTV). The average maximum percent dose difference was observed in brainstem (26.54% ± 27.027), and the average mean dose difference has found at same organ (1.6% ± 1.66). CONCLUSION: The change in image-registration method definitely produces dose variance, and is significantly more what depending on the target location. The volume size of OARs, however, was not statistical significantly correlated with dose variance.

Cartilage MRI T2∗ relaxation time and perfusion changes of the knee in a 5/6 nephrectomy rat model of chronic kidney disease.

OBJECTIVE: Chronic kidney disease (CKD) is characterized by metabolic disturbances in calcium and phosphorus homeostasis as kidney function declines. Alterations in blood perfusion in bone resulting from arteriosclerosis of bone vessels may relate to the progression of CKD. Herein, change in dynamic contrast enhanced (DCE) MRI parameters (A: amplitude, kel: elimination constant, and kep: permeability rate constant) and MRI T2∗ relaxation time of the knee cartilage were measured in a rodent nephrectomy model in order to (1) examine the relationship of peripheral blood perfusion to CKD and (2) demonstrate the feasibility of using DCE-MRI parameters and MRI T2∗ as imaging biomarkers to monitor disease progression. DESIGN: Two groups of male Sprague-Dawley rats received either (1) no intervention or (2) 5/6 nephrectomy. RESULTS: We found that the CKD group (compared with the control group) had lower A and kel values and similar kep value in the lateral and medial articular cartilages beginning at 12 weeks (P < 0.05); statistically significantly higher T2∗ values in the lateral and medial articular cartilages beginning at 18 weeks (P < 0.05); statistically significantly decreased inner luminal diameter of the popliteal artery, and altered structure of the lateral and medial articular cartilages (P < 0.05). CONCLUSION: Perfusion deficiency and CKD may be related. DCE parameters and MRI T2∗ could serve as imaging biomarkers of cartilage degeneration in CKD progression.

Higher serum uric acid level increases risk of prehypertension in subjects with normal glucose tolerance, but not pre-diabetes and diabetes.

Although the association between serum uric acid (SUA) levels and prehypertension has been reported in previous studies, it is unknown whether their relationship is similar in subjects with diabetes, pre-diabetes and normal glucose tolerance (NGT). This study thus aimed to investigate the relationship between SUA and prehypertension in subjects with different glycemic status, including NGT, pre-diabetes and diabetes. A total of 12 010 participants were included after excluding subjects with blood pressure ⩾140/90 mm Hg, history of hypertension, leukaemia, lymphoma, hypothyroidism, medication for hypertension and hyperuricemia and missing data. Subjects were divided into four groups based on SUA quartiles (male Q1: ⩽345.0, Q2: 345.0-392.6, Q3: 392.6-440.2, Q4: ⩾440.2 µmol l(-1) and female Q1: ⩽249.8, Q2: 249.8-285.5, Q3: 285.5-333.1, Q4: ⩾333.1 µmol l(-1)). Diabetes, pre-diabetes and NGT were assessed according to the 2010 American Diabetes Association diagnostic criteria. Normotension and prehypertension were defined according to the JNC-7 (The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) criteria. The SUA was significantly higher in prehypertensive subjects as compared with normotensive subjects. SUA, as a continuous variable, was positively associated with prehypertension in subjects with NGT but not pre-diabetes and diabetes. Besides, NGT subjects with the highest quartile of SUA exhibited a higher risk of prehypertension after adjustment for other confounding factors. In pre-diabetes and diabetes groups, none of SUA quartiles was significantly related to prehypertension. SUA was significantly associated with an increased risk of prehypertension in subjects with NGT but insignificantly in subjects with pre-diabetes and diabetes.

The metabolome profiling and pathway analysis in metabolic healthy and abnormal obesity.

OBJECTIVES: Mechanisms of the development of abnormal metabolic phenotypes among obese population are not yet clear. In this study, we aimed to screen metabolomes of both healthy and subjects with abnormal obesity to identify potential metabolic pathways that may regulate the different metabolic characteristics of obesity. METHODS: We recruited subjects with body mass index (BMI) over 25 from the weight-loss clinic of a central hospital in Taiwan. Metabolic healthy obesity (MHO) is defined as without having any form of hyperglycemia, hypertension and dyslipidemia, while metabolic abnormal obesity (MAO) is defined as having one or more abnormal metabolic indexes. Serum-based metabolomic profiling using both liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry of 34 MHO and MAO individuals with matching age, sex and BMI was performed. Conditional logistic regression and partial least squares discriminant analysis were applied to identify significant metabolites between the two groups. Pathway enrichment and topology analyses were conducted to evaluate the regulated pathways. RESULTS: A differential metabolite panel was identified to be significantly differed in MHO and MAO groups, including L-kynurenine, glycerophosphocholine (GPC), glycerol 1-phosphate, glycolic acid, tagatose, methyl palmitate and uric acid. Moreover, several metabolic pathways were relevant in distinguishing MHO from MAO groups, including fatty acid biosynthesis, phenylalanine metabolism, propanoate metabolism, and valine, leucine and isoleucine degradation. CONCLUSION: Different metabolomic profiles and metabolic pathways are important for distinguishing between MHO and MAO groups. We have identified and discussed the key metabolites and pathways that may prove important in the regulation of metabolic traits among the obese, which could provide useful clues to study the underlying mechanisms of the development of abnormal metabolic phenotypes.

Single-step deposition of high-mobility graphene at reduced temperatures.

Current methods of chemical vapour deposition (CVD) of graphene on copper are complicated by multiple processing steps and by high temperatures required in both preparing the copper and inducing subsequent film growth. Here we demonstrate a plasma-enhanced CVD chemistry that enables the entire process to take place in a single step, at reduced temperatures (<420 °C), and in a matter of minutes. Growth on copper foils is found to nucleate from arrays of well-aligned domains, and the ensuing films possess sub-nanometre smoothness, excellent crystalline quality, low strain, few defects and room-temperature electrical mobility up to (6.0±1.0) × 10(4) cm(2) V(-1) s(-1), better than that of large, single-crystalline graphene derived from thermal CVD growth. These results indicate that elevated temperatures and crystalline substrates are not necessary for synthesizing high-quality graphene.

The risk of colorectal cancer is related to frequent hospitalization of IBD in an Asian population: results from a nationwide study.

BACKGROUND: The occurrence of inflammatory bowel disease (IBD) is higher in Western countries and is increasing worldwide. The incidence of IBDs is about nearly 20-fold in Western countries than Asia and has risen in Taiwan over the past few decades. Epidemiological studies have demonstrated an increased risk of colorectal cancer (CRC) in patients with IBD. The prevalence of IBD as well as IBD-associated CRC is changing and the risk of CRC in patients with IBD appears to be greater in Western countries, but CRC risk in IBD patients is less well understood in low endemic areas, such as Asia. METHODS: This population-based cohort study collected data from the Taiwan Health Insurance Research Database (from January 1998 to December 2011). In total, 10 650 patients with confirmed diagnosis of IBD served as the IBD cohort and 42 600 non-IBD subjects were enrolled. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) were used to assess the risk of CRC. RESULTS: The incidence of CRC was slightly lower in the IBD cohort compared with that in the non-IBD cohort (0.94 vs. 1.13 per 1000 person-years), with an adjusted HR of 0.99 (95% CI: 0.71-1.37). More than four hospitalizations were associated with a significantly higher risk of CRC in IBD patients in the Cox model (adjusted HR = 3.48, 95% CI: 1.59-7.63). CONCLUSIONS: The risk for CRC was not increased among IBD patients overall, but appeared to be increased with cumulative frequency of hospitalizations for IBD.

Phosphorylation of glycogen synthase kinase-3ß in metabolically abnormal obesity affects immune stimulation-induced cytokine production.

BACKGROUND: Obesity is a severe health problem worldwide, which leads to multiple comorbidities including type 2 diabetes mellitus and cardiovascular diseases. Inflammation has been found to be an important characteristic of adipose tissue in obese subjects. However, obesity is also associated with compromised immune responses to infections and the impact of obesity on immune function has not been fully understood. SUBJECTS/METHODS: To clarify the role of obesity in the immune responses, we investigated the Toll-like receptor (TLR)-induced cytokine secretion by leukocytes from obese and lean subjects. We also investigated the relationship between insulin-induced intracellular signaling and cytokine production using peripheral blood mononuclear cells (PBMCs) and a monocytic cell line THP-1. RESULTS: We found decreased TLR-induced interferon-γ, interleukin-6 (IL-6) and tumor necrosis factor-α secretions and elevated IL-10 secretion by leukocytes from obese subjects when compared with lean controls. PBMCs from obese subjects showed enhanced basal Akt and glycogen synthase kinase-3ß (GSK-3ß) phosphorylation, which did not further increase with insulin and lipopolysaccharide (LPS) stimulation. We also found that LPS-induced IκBα degradation was inhibited in PBMCs from obese subjects. By using THP-1 cells with GSK-3ß knockdown or cells treated with hyperinsulinemic and high-fatty acid conditions, we found that LPS-induced nuclear factor κB (NF-κB) activation was inhibited and cyclic adenosine monophosphate response element-binding protein (CREB) activation was enhanced. CONCLUSIONS: These findings indicate that GSK-3ß is important in the regulation of NF-κB and CREB activation in leukocytes under the metabolic condition of obesity. Our study revealed a key mechanism through which metabolic abnormalities compromise leukocyte functions in people with obesity.

mRNA Transcript abundance during plant growth and the influence of Li(+) exposure.

Lithium (Li) toxicity in plants is, at a minimum, a function of Li(+) concentration, exposure time, species and growth conditions. Most plant studies with Li(+) focus on short-term acute exposures. This study examines short- and long-term effects of Li(+) exposure in Arabidopsis with Li(+) uptake studies and measured shoot mRNA transcript abundance levels in treated and control plants. Stress, pathogen-response and arabinogalactan protein genes were typically more up-regulated in older (chronic, low level) Li(+)-treatment plants and in the much younger plants from acute high-level exposures. The gene regulation behavior of high-level Li(+) resembled prior studies due to its influence on: inositol synthesis, 1-aminocyclopropane-1-carboxylate synthases and membrane ion transport. In contrast, chronically-exposed plants had gene regulation responses that were indicative of pathogen, cold, and heavy-metal stress, cell wall degradation, ethylene production, signal transduction, and calcium-release modulation. Acute Li(+) exposure phenocopies magnesium-deficiency symptoms and is associated with elevated expression of stress response genes that could lead to consumption of metabolic and transcriptional energy reserves and the dedication of more resources to cell development. In contrast, chronic Li(+) exposure increases expression signal transduction genes. The identification of new Li(+)-sensitive genes and a gene-based "response plan" for acute and chronic Li(+) exposure are delineated.

Hepatitis C transmission from viremic donors in hematopoietic stem cell transplant.

Transmission of hepatitis C virus (HCV) to recipients of hematopoietic stem cell transplant (HSCT) occurs frequently from HCV viremic donors and causes complications. Here, we report the outcomes of 3 cases from our 265 allogeneic HSCTs, whose donors had HCV infections. Successful prevention of HCV transmission was noted in 1 recipient by pretreatment of the donor with peginterferon/ribavirin to undetectable levels of HCV viremia before stem cell harvest. This case stressed the important role of effective antiviral therapy and HCV RNA seronegativity before cell harvest for prevention of HCV transmission in HSCT.

High-speed atomic force microscope based on an astigmatic detection system.

High-speed atomic force microscopy (HS-AFM) enables visualizing dynamic behaviors of biological molecules under physiological conditions at a temporal resolution of 1s or shorter. A small cantilever with a high resonance frequency is crucial in increasing the scan speed. However, detecting mechanical resonances of small cantilevers is technically challenging. In this study, we constructed an atomic force microscope using a digital versatile disc (DVD) pickup head to detect cantilever deflections. In addition, a flexure-guided scanner and a sinusoidal scan method were implemented. In this work, we imaged a grating sample in air by using a regular cantilever and a small cantilever with a resonance frequency of 5.5 MHz. Poor tracking was seen at the scan rate of 50 line/s when a cantilever for regular AFM imaging was used. Using a small cantilever at the scan rate of 100 line/s revealed no significant degradation in the topographic images. The results indicate that a smaller cantilever can achieve a higher scan rate and superior force sensitivity. This work shows the potential for using a DVD pickup head in future HS-AFM technology.

Decreased expression of PIAS1 and PIAS3 in essential thrombocythemia patients.

Gain of function mutation of Janus kinase 2 (JAK2V617F) has been identified in Philadelphia-negative myeloproliferative diseases; about half of essential thrombocythemia (ET) patients harbor this mutation. The activated JAK-STAT pathway promotes cell proliferation, differentiation and anti-apoptosis. We studied the role of negative regulators of the JAK-STAT pathway, PIAS, and SOCS in ET patients. Twenty ET patients and 20 healthy individuals were enrolled in the study. Thirteen of the ET patients harbored the JAK2V617F mutation based on mutation analysis. Quantitative-PCR was applied to assay the expression of SOCS1, SOCS3, PIAS1, PIAS3. The expression levels of PIAS1 and PIAS3 were significantly lower in ET groups than that in normal individuals. There was no significant difference between JAK2V617F (+) and JAK2V617F (-) patients. SOCS1 and SOCS3 expression did not differ between ET patients and normal individuals, or between JAK2V617F (+) and JAK2V617F (-) patients. We suggest that failed negative regulators of the JAK-STAT pathway take part in the pathomechanism of ET.

Operation of astigmatic-detection atomic force microscopy in liquid environments.

The astigmatic detection system (ADS) based on commercial optical pickup head was demonstrated to achieve a sub-nanometer sensitivity in detecting the vertical movement of an object surface in air. The detection laser spot of the ADS was sub-µm and the detection bandwidth was over 80 MHz. These advantages allow detection of high-frequency mechanical resonance of very small objects, which would have many important applications in nanotechnology. In this work, we optimized the operation conditions of ADS to achieve good sensitivity in aqueous solutions. We demonstrated good contrast and good spatial resolution of cancer cells in water with the optical profilometry mode. We also built an ADS-AFM (atomic force microscopy) for imaging in water. A novel cantilever holder was designed, and the spurious peaks were suppressed down to 26.0% of the real resonance peak. Most importantly, we demonstrated that the ADS-AFM could resolve single atomic steps on a graphite substrate and image soft DNA molecules on mica in water.

Central obesity in males affected by a dyslipidemia-associated genetic polymorphism on APOA1/C3/A4/A5 gene cluster.

BACKGROUND: Central obesity is a rising epidemic, and often occurs in parallel with dyslipidemia. Furthermore, enhancement of ectopic fat deposition has been observed in both human studies and animal models of altered lipidemic control. Though APOA1/C3/A4/A5 genetic polymorphisms are associated with dyslipidemia, their effect on central obesity is less known. METHOD: The anthropometric and metabolic parameters were taken from obese (body mass index (BMI) 25 kg m(-2)) and non-obese healthy (BMI <25) Taiwanese patients at the initiation weight-loss intervention and 6 months later. The effects of APOA1/C3/A4/A5 genetic polymorphisms were analyzed cross-sectionally and longitudinally. Gender contributions were specifically examined. PATIENTS: Three hundred and ninety-eight participants (obese n=262; non-obese healthy n=136) were recruited in total, and 130 obese patients underwent weight-loss treatments. RESULTS: APOA5 rs662799 minor allele carriage was associated with unfavorable metabolic profiles in obese but not non-obese individuals at baseline. Further analysis identified gender-genotype interactions in waist-hip ratio (WHR), and that one rs662799 minor allele increased 0.032 WHR unit in obese males as analyzed by linear regression adjusted for age, BMI and plasma triglyceride (TG) (95% confidence interval (CI)=0.014-0.050, P=0.001). The rs662799-associated WHR elevation resulted in increased frequency of central obesity (WHR 1.0) in rs662799 carrying obese males as analyzed by binary logistic regression adjusted for age, BMI and plasma TG (odds ratio=6.52, 95% CI=1.87-22.73, P=0.003). In contrast, APOA5 rs662799 and central obesity were no longer correlated 6 months into weight-loss treatments, owing to significant WHR reductions in male rs662799 minor allele carriers (P=0.001). Meanwhile, hypertriglyceridemia was more prevalent in both male and female obese rs662799 minor allele carriers at baseline (males, P=0.034, females, P=0.007). CONCLUSION: This study highlights the gender-specific and weight-sensitive effects of APOA5 rs662799 on central obesity in Taiwanese individuals, and that these effects are dyslipidemia-independent and weight-loss responsive.

Philadelphia-negative chromosomal evolution during treatment for chronic myeloid leukemia.

Chromosome evolution is one of the major mechanisms of disease progression and resistance in chronic myeloid leukemia (CML) patients. However, the clinical significance of chromosomal evolution in the Philadelphia (Ph)-negative clone during therapy is not fully understood. We evaluated 94 CML patients in the chronic phase of CML during treatment of the disease. Six of them had Ph-negative chromosome abnormalities during treatment. Four patients with a single abnormality and a good molecular response showed no obvious complications from the chromosomal changes, while two other patients who had complex abnormalities and previous treatment had poor outcomes. Our results highlight the need for close monitoring of this kind of patient, not only on a molecular level but also at the cytogenetic level.

Rotational positioning system adapted to atomic force microscope for measuring anisotropic surface properties.

The diverse atomic configurations induce the anisotropic surface properties. For investigating anisotropic phenomena, we developed a rotational positioning system adapted to atomic force microscope (AFM). This rotational positioning system is applied to revolve the measured sample to defined angular direction, and it composed of an inertial rotational stepper and a visual angular measurement. The inertial rotational stepper with diameter 30 mm and height 7.6 mm can be easily attached to the AFM-system built in any general optical microscope. Based on a clearance less bearing and the inertial driving method, its bidirectional angular resolution reaches 0.005° per step. For realizing a close-loop controlled angular positioning function, the visual measurement method is utilized. Through the feedback control, the angular positioning error is less than 0.01°. For verifying the system performance, we used it to investigate the anisotropic surface properties of graphite. Through a modified cantilever tip, the atomic-scale stick-slip, and the anisotropic friction phenomena can be distinctly detected.

Water solution of onion crude powder inhibits RANKL-induced osteoclastogenesis through ERK, p38 and NF-kappaB pathways.

UNLABELLED: Onion powder has been reported to decrease the ovariectomy-induced bone resorption of rats. However, the molecular mechanism of onion powder on the bone cells has not been reported. Here, we report that water solution of onion crude powder decreases the osteoclastogenesis from co-cultures of bone marrow stromal cells and macrophage cells. Additionally, water solution of onion crude powder inhibits the RANKL-induced ERK, p38 and NF-kappaB activation in macrophages. In summary, our data showed that onion powder may benefit bone through an anti-resorption effect on the osteoclasts. INTRODUCTION: A nutritional approach is important for both prevention and treatment of osteoporosis. Onion has been reported to decrease the ovariectomy-induced bone resorption. However, the functional effects of onion on the cultured osteoclasts and osteoblasts remain largely unknown. Here, we found that water solution of onion crude powder markedly inhibited the receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis through ERK, p38 and NF-kappaB pathways. Other studies were also designed to investigate the potential signaling pathways involved in onion-induced decrease in osteoclastogenesis. METHODS: The osteoclastogenesis was examined using the TRAP staining method. The MAPKs and NF-kappaB pathways were measured using Western blot analysis. A transfection protocol was used to examine NF-kappaB activity. RESULTS: Water solution of onion crude powder inhibited the RANKL plus M-CSF-induced osteoclastic differentiation from either bone marrow stromal cells or from RAW264.7 macrophage cells. Treatment of RAW264.7 macrophages with RANKL could induce the activation of ERK, p38 and NF-kappaB that was inhibited by water solution of onion crude powder. On the other hand, it did not affect the cell proliferation and differentiation of human cultured osteoblasts. CONCLUSIONS: Our data suggest that water solution of onion crude powder inhibits osteoclastogenesis from co-cultures of bone marrow stromal cells and macrophage cells via attenuation of RANKL-induced ERK, p38 and NF-kappaB activation.

The spectrum of the factor 8 (F8) defects in Taiwanese patients with haemophilia A.

Haemophilia A (HA) is an X-linked recessive bleeding disorder caused by various types of pathological defects in the factor VIII gene (F8), which encodes coagulation factor VIII (FVIII). To date, several studies on the spectra of F8 defects have been performed in Western populations, but similar studies in Asian races are scarce. Here, we report the distribution of the mutations within the F8 gene in 31 Taiwanese unrelated HA patients (19 severe and 10 moderate/mild males and two severe females). Of these, 12 (38.7%) and one (3.2%) severe males were genotyped with the recurrent IVS22 and IVS1 inversion, respectively, similar to that in general populations (IVS22: 40-50%; IVS1: 2-5%). The F8 defects in the remaining 18 inversion-negative patients cover a wide spectrum, in which 17 different mutations were identified (10 missense and three nonsense mutations, and two small and two large deletions). Eleven of these mutations are novel: seven caused missense substitutions and four resulted in truncated proteins. To assess the putative pathogenetic impacts of the newly amino acid substitutions, computer analyses were performed based on molecular 3D modelling. The degree of conservation in cross-species FVIIIs and the position in known functional FVIII regions were studied. The novel missense mutations found in our series all occurred at evolutionary conserved residues that may carry a functional importance in our analyses. The results of this study add the short list of Taiwanese/Chinese F8 mutations, and will enhance our understanding of the molecular basis of FVIII function and the mechanism underlying HA.