Exercise, Processing Speed, and Subsequent Falls: A Secondary Analysis of a 12-Month Randomized Controlled Trial.

BACKGROUND: Strength and balance retraining exercises reduce the rate of subsequent falls in community-dwelling older adults who have previously fallen. Exercise can also improve cognitive function, including processing speed. Given processing speed predicts subsequent falls, we aimed to determine whether improved processing speed mediated the effects of the Otago Exercise Program on the rate of subsequent: (i) total falls, (ii) non-injurious falls, (iii) moderate injurious falls, and (iv) serious injurious falls. METHOD: A secondary complete case analysis of a 12-month, single-blind, randomized clinical trial among 256 of 344 adults aged at least 70 years who fell in the previous 12 months. Participants were randomized 1:1 to receive usual care plus the Otago Exercise Program (n = 123) or usual care (n = 133), consisting of fall prevention care provided by a geriatrician. The primary outcome was self-reported number of falls over 12 months (ie, rate of falls). Processing speed was assessed at baseline and at 12 months by the Digit Symbol Substitution Test (DSST). Causal mediation analyses were conducted using quasi-Bayesian estimates and 95% confidence intervals. RESULTS: Exercise significantly reduced the rate of subsequent moderate injurious falls (IRR = 0.49; 95% CI: 0.31, 0.77; p = .002) and improved processing speed (estimated mean difference: 1.16 points; 95% CI: 0.11, 2.21). Improved DSST mediated the effect of exercise on the rate of subsequent moderate injurious falls (estimate: -0.06; 95% CI: -0.15, -0.001; p = .036). CONCLUSION: Improved processing speed may be a mechanism by which exercise reduces subsequent moderate injurious falls in older adults who fell previously. CLINICAL TRIALS REGISTRATION NUMBER: ClinicalTrials.gov Protocol Registration System:NCT01029171: https://clinicaltrials.gov/ct2/show/NCT01029171NCT00323596: https://clinicaltrials.gov/ct2/show/NCT00323596.

First Measurements of Absolute Branching Fractions of the Ξ_{c}

We present the first measurements of absolute branching fractions of Ξ_{c}^{0} decays into Ξ^{-}π^{+}, ΛK^{-}π^{+}, and pK^{-}K^{-}π^{+} final states. The measurements are made using a dataset comprising (772±11)×10^{6} BB[over ¯] pairs collected at the ϒ(4S) resonance with the Belle detector at the KEKB e^{+}e^{-} collider. We first measure the absolute branching fraction for B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0} using a missing-mass technique; the result is B(B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0})=(9.51±2.10±0.88)×10^{-4}. We subsequently measure the product branching fractions B(B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0})B(Ξ_{c}^{0}→Ξ^{-}π^{+}), B(B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0})B(Ξ_{c}^{0}→ΛK^{-}π^{+}), and B(B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0})B(Ξ_{c}^{0}→pK^{-}K^{-}π^{+}) with improved precision. Dividing these product branching fractions by the result for B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0} yields the following branching fractions: B(Ξ_{c}^{0}→Ξ^{-}π^{+})=(1.80±0.50±0.14)%, B(Ξ_{c}^{0}→ΛK^{-}π^{+})=(1.17±0.37±0.09)%, and B(Ξ_{c}^{0}→pK^{-}K^{-}π^{+})=(0.58±0.23±0.05)%. For the above branching fractions, the first uncertainties are statistical and the second are systematic. Our result for B(Ξ_{c}^{0}→Ξ^{-}π^{+}) can be combined with Ξ_{c}^{0} branching fractions measured relative to Ξ_{c}^{0}→Ξ^{-}π^{+} to yield other absolute Ξ_{c}^{0} branching fractions.

Histamine drives severity of innate inflammation via histamine 4 receptor in murine experimental colitis.

Ulcerative colitis (UC) patients exhibit elevated histamine, but how histamine exacerbates disease is unclear as targeting histamine 1 receptor (H1R) or H2R is clinically ineffective. We hypothesized that histamine functioned instead through the other colon-expressed histamine receptor, H4R. In humans, UC patient biopsies exhibited increased H4R RNA and protein expression over control tissue, and immunohistochemistry showed that H4R was in proximity to immunopathogenic myeloperoxidase-positive neutrophils. To characterize this association further, we employed both the oxazolone (Ox)- and dextran sulfate sodium (DSS)-induced experimental colitis mouse models and also found upregulated H4R expression. Mast cell (MC)-derived histamine and H4R drove experimental colitis, as H4R-/- mice had lower symptom scores, neutrophil-recruitment mediators (colonic interleukin-6 (IL-6), CXCL1, CXCL2), and mucosal neutrophil infiltration than wild-type (WT) mice, as did MC-deficient KitW-sh/W-sh mice reconstituted with histidine decarboxylase-deficient (HDC-/-) bone marrow-derived MCs compared with WT-reconstituted mice; adaptive responses remained intact. Furthermore, Rag2-/- × H4R-/- mice had reduced survival, exacerbated colitis, and increased bacterial translocation than Rag2-/- mice, revealing an innate protective antibacterial role for H4R. Taken together, colonic MC-derived histamine initiates granulocyte infiltration into the colonic mucosa through H4R, suggesting alternative therapeutic targets beyond adaptive immunity for UC.

GATA3 interacts with and stabilizes HIF-1α to enhance cancer cell invasiveness.

This corrects the article DOI: 10.1038/onc.2017.8.

Oncoprotein ZNF322A transcriptionally deregulates alpha-adducin, cyclin D1 and p53 to promote tumor growth and metastasis in lung cancer.

This corrects the article DOI: 10.1038/onc.2015.296.

Oncoprotein ZNF322A transcriptionally deregulates alpha-adducin, cyclin D1 and p53 to promote tumor growth and metastasis in lung cancer.

This corrects the article DOI: 10.1038/onc.2015.296.

GATA3 interacts with and stabilizes HIF-1α to enhance cancer cell invasiveness.

GATA binding protein 3 (GATA3) is indispensable in development of human organs. However, the role of GATA3 in cancers remains elusive. Hypoxia inducible factor (HIF)-1 plays an important role in pathogenesis of human cancers. Regulation of HIF-1α degradation is orchestrated through collaboration of its interacting proteins. In this study, we discover that GATA3 is upregulated in head and neck squamous cell carcinoma (HNSCC) and is an independent predictor for poor disease-free survival. GATA3 promotes invasive behaviours of HNSCC and melanoma cells in vitro and in immunodeficient mice. Mechanistically, GATA3 physically associates with HIF-1α under hypoxia to inhibit ubiquitination and proteasomal degradation of HIF-1α, which is independent of HIF-1α prolyl hydroxylation. Chromatin immunoprecipitation assays show that the GATA3/HIF-1α complex binds to and regulates HIF-1 target genes, which is also supported by the microarray analysis. Notably, the GATA3-mediated invasiveness can be significantly reversed by HIF-1α knockdown, suggesting a critical role of HIF-1α in the underlying mechanism of GATA3-mediated effects. Our findings suggest that GATA3 stabilizes HIF-1α to enhance cancer invasiveness under hypoxia and support the GATA3/HIF-1α axis as a potential therapeutic target for cancer treatment.

Oxygen Uptake Efficiency Slope Predicts Major Cardiac Events in Patients With End-Stage Heart Failure.

INTRODUCTION: Oxygen uptake efficiency slope (OUES) has been shown as a predictor of stable heart failure (HF) survival. However, there is a lack of evidence for end-stage HF. OBJECTIVES: We aimed to investigate the prognostic value of OUES in end-stage HF patients. METHODS: The study design was a retrospective cohort. End-staged HF patients who had cardiopulmonary exercise testing (CPET) for evaluation between 2004 and 2009 were included. The primary outcomes were cardiac death and heart transplantation. The independent survival predictors were determined using Cox regression hazard model adjusted for demographics, New York Heart Association (NYHA) classification, medication, and left ventricular ejection fraction (LVEF). The Kaplan-Meier survival curves and log-rank test were used. Probability values less than .05 were considered significant. RESULTS: Mean age of the 128 patients was 50 ± 12 years and 93 were male. Mean LVEF was 23% ± 9%. Forty-three subjects suffered cardiac events (5 cardiac deaths and 38 urgent heart transplantations) during the 2-year follow-up period. Cox regression indicated that OUES and diuretics were significant predictors of 2-year survival, although peak oxygen uptake and ventilatory equivalent of carbon dioxide were not. Patients with high OUES (≥1.6) had a higher survival rate (P < .001; odds ratio [OR], 13.10; 95% confidence interval [CI], 3.30-58.63). The Kaplan-Meier curves show survival was significantly higher in those with OUES ≥1.6. CONCLUSIONS: OUES might be an aid in prognosis of patients with end-stage HF and useful in the assessment of patients unable to perform maximal exercise testing.

A Facile and Low-Cost Method to Enhance the Internal Quantum Yield and External Light-Extraction Efficiency for Flexible Light-Emitting Carbon-Dot Films.

Solution-processed, non-toxic carbon dots (CDs) have attracted much attention due to their unique photoluminescence (PL) properties. They are promising emissive layers for flexible light-emitting devices. To this end, the CDs in pristine aqueous solutions need to be transferred to form solid-state thin films without sacrificing their original PL characteristics. Unfortunately, solid-state PL quenching induced by extra non-radiative (NR) energy transfer among CDs would significantly hinder their practical applications in optoelectronics. Here, a facile, low-cost and effective method has been utilized to fabricate high-performance CD/polymer light-emitting flexible films with submicron-structured patterns. The patterned polymers can serve as a solid matrix to disperse and passivate CDs, thus achieving high internal quantum yields of 61%. In addition, they can act as an out-coupler to mitigate the waveguide-mode losses, approximately doubling the external light-extraction efficiency. Such CD/polymer composites also exhibit good photo-stability, and thus can be used as eco-friendly, low-cost phosphors for solid-state lighting.

Cognitive status is a determinant of health resource utilization among individuals with a history of falls: a 12-month prospective cohort study.

SUMMARY: Falls are a costly public health problem worldwide. The literature is devoid of prospective data that identifies factors among fallers that significantly drive health care resource utilization. We found that cognitive function--specifically, executive functions--and cognitive status are significant determinants of health resource utilization among older fallers. INTRODUCTION: Although falls are costly, there are no prospective data examining factors among fallers that drive health care resource utilization. We identified key determinants of health resource utilization (HRU) at 6 and 12 months among older adults with a history of falls. Specifically, with the increasing recognition that cognitive impairment is associated with increased falls risk, we investigated cognition as a potential driver of health resource utilization. METHODS: This 12-month prospective cohort study at the Vancouver Falls Prevention Clinic (n = 319) included participants with a history of at least one fall in the previous 12 months. Based on their cognitive status, participants were divided into two groups: (1) no mild cognitive impairment (MCI) and (2) MCI. We constructed two linear regression models with HRU at 6 and 12 months as the dependent variables for each model, respectively. Predictors relating to mobility, global cognition, executive functions, and cognitive status (MCI versus no MCI) were examined. Age, sex, comorbidities, depression status, and activities of daily living were included regardless of statistical significance. RESULTS: Global cognition, comorbidities, working memory, and cognitive status (MCI versus no MCI ascertained using the Montreal Cognitive Assessment (MoCA)) were significant determinants of total HRU at 6 months. The number of medical comorbidities and global cognition were significant determinants of total HRU at 12 months. CONCLUSION: MCI status was a determinant of HRU at 6 months among older adults with a history of falls. As such, efforts to minimize health care resource use related to falls, it is important to tailor future interventions to be effective for people with MCI who fall. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01022866.

Oncoprotein ZNF322A transcriptionally deregulates alpha-adducin, cyclin D1 and p53 to promote tumor growth and metastasis in lung cancer.

ZNF322A encoding a classical Cys2His2 zinc finger transcription factor was previously revealed as a potential oncogene in lung cancer patients. However, the oncogenic role of ZNF322A and its underlying mechanism in lung tumorigenesis remain elusive. Here we show ZNF322A protein overexpression in 123 Asian and 74 Caucasian lung cancer patients. Multivariate Cox regression analysis indicated that ZNF322A was an independent risk factor for a poor outcome in lung cancer, corroborating the Kaplan-Meier results that patients with ZNF322A protein overexpression had significantly poorer overall survival than other patients. Overexpression of ZNF322A promoted cell proliferation and soft agar growth by prolonging cell cycle in S phase in multiple lung cell lines, including the immortalized lung cell BEAS-2B. In addition, ZNF322A overexpression enhanced cell migration and invasion, whereas knockdown of ZNF322A reduced cell growth, invasion and metastasis abilities in vitro and in vivo. Quantitative proteomic analysis revealed potential ZNF322A-regulated downstream targets, including alpha-adducin (ADD1), cyclin D1 (CCND1), and p53. Using luciferase promoter activity assay combined with site-directed mutagenesis and sequential chromatin immunoprecipitation-PCR assay, we found that ZNF322A could form a complex with c-Jun and cooperatively activate ADD1 and CCND1 but repress p53 gene transcription by recruiting differential chromatin modifiers, such as histone deacetylase 3, in an AP-1 element dependent manner. Reconstitution experiments indicated that CCND1 and p53 were important to ZNF322A-mediated promotion of cell proliferation, whereas ADD1 was necessary for ZNF322A-mediated cell migration and invasion. Our results provide compelling evidence that ZNF322A overexpression transcriptionally dysregulates genes involved in cell growth and motility therefore contributes to lung tumorigenesis and poor prognosis.

A fixed denture for a child with epidermolysis bullosa simplex.

AIM: To report the caries treatment and delivery of a fixed denture for a 3-year-old girl with epidermolysis bullosa simplex (EBS). CASE REPORT: EBS is manifested on the skin or mucous membranes where skin separation is easily induced by trauma. Full- mouth rehabilitation under in-patient general anaesthesia was performed to the patient in conjunction with proper pre- and postoperative care. A fixed denture was fabricated and installed to replace the extracted teeth without later causing irritation on the mucosa. The prosthesis restored aesthetics and provided comfort without imposing the burden of compliance on the patient. CONCLUSION: Aided by meticulous pre- and postoperative care and oral hygiene reinforcement, comprehensive dental treatment coupled with fixed denture delivery can greatly improve the life quality and aesthetics for children with EBS.

Prognostic value of oxygen consumption and ventilatory equivalent slope in female candidates referred for heart transplantation--experience of a single Asian center.

BACKGROUND: Ventilatory equivalent (ventilation/CO2 production, VE/VCO2) slope has been suggested to be a much more accurate predicator than peak oxygen consumption (VO2) during exercise for prognosis in patients with heart failure. However, patients tested were predominately male. METHODS: To investigate whether peak VO2 and VE/VCO2 slope predict the prognosis of female patients with heart failure, we retrospectively collected data of 39 female candidates referred for heart transplantation (HTx) from 2004 to 2011. Both peak VO2 and VE/VCO2 slope were obtained from the results of an exercise pulmonary function test. The outcome was death or mechanical devices implantation or HTx. Logistic regression was used for data analysis. RESULTS: Mean age and heart failure survival score were 55.8 ± 13.7 years and 7.3 ± 0.7, respectively. Each increment of VE/VCO2 slope decreased 2-year event-free rate (odds ratio [OR] = 0.88, 95% confidence interval [CI] = 0.79 to 0.98) in the female group. The predictions of VE/VCO2 slope for 1-year event-free survival did not reach statistical significance (OR = 0.92, 95% CI = 0.84 to 1.00). On the other hand, peak VO2 was not a strong predictor for 1- and 2-year event-free survival (OR = 1.22 and 1.16, 95% CI = 0.96 to 1.55 and 0.94 to 1.44, respectively). CONCLUSIONS: Impairment in exercise ventilation holds a clinical and long-term prognostic impact in female patients with heart failure. The role of peak VO2 during exercise in prognostic prediction among the cohort should be further investigated.

Movement of entomophagous arthropods in agricultural landscapes: links to pest suppression.

Entomophagous arthropods can provide valuable biological control services, but they need to fulfill their life cycle in agricultural landscapes often dominated by ephemeral and disturbed habitats. In this environment, movement is critical to escape from disturbances and to find resources scattered in space and time. Despite considerable research effort in documenting species movement and spatial distribution patterns, the quantification of arthropod movement has been hampered by their small size and the variety of modes of movement that can result in redistribution at different spatial scales. In addition, insight into how movement influences in-field population processes and the associated biocontrol services is limited because emigration and immigration are often confounded with local-scale population processes. More detailed measurements of the habitat functionality and movement processes are needed to better understand the interactions between species movement traits, disturbances, the landscape context, and the potential for entomophagous arthropods to suppress economically important pests.

Limits on spin-independent couplings of WIMP dark matter with a p-type point-contact germanium detector.

We report new limits on a spin-independent weakly interacting massive particle (WIMP)-nucleon interaction cross section using 39.5 kg days of data taken with a p-type point-contact germanium detector of 840 g fiducial mass at the Kuo-Sheng Reactor Neutrino Laboratory. Crucial to this study is the understanding of the selection procedures and, in particular, the bulk-surface events differentiation at the sub-keV range. The signal-retaining and background-rejecting efficiencies were measured with calibration gamma sources and a novel n-type point-contact germanium detector. Part of the parameter space in the cross section versus WIMP-mass implied by various experiments is probed and excluded.

Examining the relationship between specific cognitive processes and falls risk in older adults: a systematic review.

This systematic review aims to establish which cognitive domains are associated with falls or falls risk. Recent evidence suggests that impaired cognition increases seniors' risk of falling. The purpose of this review was to identify the cognitive domains that are significantly associated with falls or falls risk in older adults. We conducted a systematic review of peer-reviewed journal articles published from 1948 to present, focusing on studies investigating different domains of cognitive function and their association with falls or falls risk in adults aged 60 years or older. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we completed a comprehensive search of MEDLINE, PubMed, and EMBASE databases to identify studies examining the association between cognitive function and falls or falls risk. With an expert in the field, we developed a quality assessment questionnaire to rate the quality of the studies included in this systematic review. Twenty-five studies were included in the review. We categorized studies based on two related but distinct cognitive domains: (1) executive functions or (2) dual-task ability. Twelve studies reported a significant association between executive functions and falls risk. Thirteen studies reported that dual-task performance is a predictor of falls or falls risk in older adults. Three studies did not report an association between cognition and falls risk. Consistent evidence demonstrated that executive functions and dual-task performance were highly associated with falls or falls risk. The results from this review will aid healthcare professionals and researchers in developing innovative screening and treatment strategies for mitigating falls risk by targeting specific cognitive domains.

A comparative study of loratadine syrup and cyproheptadine HCL solution for treating perennial allergic rhinitis in Taiwanese children aged 2-12 years.

We assessed the efficacy of loratadine syrup compared with cyproheptadine HCl solution for treating children aged from 2 to 12 years with perennial allergic rhinitis (PAR) in Taiwan. Sixty children with mite-induced PAR were enrolled and randomly placed into two treatment groups: loratadine syrup or cyproheptadine HCl solution. Treatment efficacy and symptom changes from baseline to post-treatment were evaluated by total symptom scores and visual analogue scales (VAS) during a 2-week period. There were no differences in age, gender, height, or weight between the two groups. After 2 weeks of treatment, there was a significantly greater reduction in symptom scores in the loratadine group than in the cyproheptadine group (p<0.001). Clinical and subjective VAS showed significant differences in percentage changes from baseline between the loratadine and cyproheptadine groups at all time points (all p<0.001, in favor of loratadine). Clinical VAS change at week 1: 95.1 vs 11.3; subjective VAS change at week 1: 88.6 vs 13.6; clinical VAS change at week 2: 125.5 vs 18.3; subjective VAS change at week 2: 101.4 vs 7.1. Thus, loratadine was superior to cyproheptadine for alleviating both nasal and non-nasal symptoms of perennial allergic rhinitis in Taiwanese children aged 2-12 years.

Effects of different contacting pressure on the transfer function between finger photoplethysmographic and radial blood pressure waveforms.

BACKGROUND: The blood pressure (BP) waveform is suggested to reflect the whole-body blood supply distribution, but its non-invasive assessment is not sufficiently user friendly for practical applications. The present authors studied the correlation between BP and photoplethysmography (PPG) waveforms, with the aim of determining the optimal range for contact pressure stimulation (PS) to produce a reliable transfer function in their harmonic parameters. METHODS: Finger PPG and radial-artery BP signals were measured simultaneously and noninvasively on healthy volunteers (n = 45). PS of 0-200 mmHg was applied to the finger, and 1 min data sequences were recorded. In frequency-domain analysis, linear regression was applied to the calculated amplitude ratios or the first five harmonics between BP and PPG waveforms. RESULTS: In the 60 mmHg-PS group, the BP-PPG regression of amplitude ratios was highest, and the agreements between them were also the best verified by Bland-Altman analysis. CONCLUSION: In the present study, frequency-domain analysis was performed to study the correlation between BP and PPG waveforms. Differences in pressure-induced-vasodilation responses underlie the different BP-PPG waveform correlations obtained by applying different PSs. The non-invasively derived PPG parameters might help to provide an easier method to acquire the radial-artery BP waveform, and hence broaden the application of BP waveform analysis.

A ZnO-nanowire phototransistor prepared on glass substrates.

The fabrication of a phototransistor via the bridging of two prefabricated electrodes with a laterally grown ZnO nanowire is reported. It was found that the fabricated device is an n-channel enhancement-mode phototransistor with a dark carrier concentration of 6.34 × 10(17) cm(-3) when the gate voltage is biased at 5 V. With an incident-light wavelength of 360 nm and a zero gate bias, it was found that the noise equivalent power and normalized detectivity (D*) of the fabricated ZnO phototransistor were 6.67 × 10(-17) W and 1.27 × 10(13) cm Hz(0.5) W(-1), respectively. It was also found that the current in the device can be modulated efficiently by tuning the wavelength of the excitation source.

PINT: Pathways INtegration Tool.

New pathway databases generally display pathways by retrieving information from a database dynamically. Some of them even provide their pathways in SBML or other exchangeable formats. Integrating these models is a challenging work, because these models were not built in the same way. Pathways integration Tool (PINT) may integrate the standard SBML files. Since these files may be obtained from different sources, any inconsistency in component names can be revised by using an annotation editor upon uploading a pathway model. This integration function greatly simplifies the building of a complex model from small models. To get new users started, about 190 curated public models of human pathways were collected by PINT. Relevant models can be selected and sent to the workbench by using a user-friendly query interface, which also accepts a gene list derived from high-throughput experiments. The models on the workbench, from either a public or a private source, can be integrated and painted. The painting function is useful for highlighting important genes or even their expression level on a merged pathway diagram, so that the biological significance can be revealed. This tool is freely available at http://csb2.ym.edu.tw/pint/.