Background and purpose
Restless legs syndrome (RLS) is an underestimated movement disorder in patients with end‐stage renal disease (ESRD). Several clinical and laboratory factors were inconsistently ...reported to associate with RLS. We aim to perform a large‐scale multicenter study to investigate the possible associated risk factors of RLS in patients with ESRD in Taiwan, a country with the highest incidence of uremia in the world.
Methods
From October 2009 to October 2011, we constitutively recruited 1130 patients with ESRD from 17 hemodialysis centers. Demographic, laboratory data, presence and severity of RLS were collected. Odds ratios (ORs) were estimated by logistic regression models.
Results
We found the prevalence of RLS to be 25.3% in patients with ESRD. Having type 2 diabetes OR = 3.61 (2.27–5.77), P < 0.01, low serum transferrin saturation OR = 1.42 (1.01–2.03), P < 0.05 and duration of dialysis OR = 1.09 (1.03–1.14), P < 0.01 were associated with RLS. In contrast, high serum hemoglobin level was inversely associated with RLS OR = 0.61 (0.40–0.89), P < 0.05. RLS has a significant impact on sleep quality in dialysis patients. Among patients with RLS, history of type 2 diabetes OR = 4.04 (1.65–10.79), P < 0.05, low serum hemoglobin level OR = 5.41 (2.43–13.12), P < 0.01 and duration of dialysis OR = 1.01 (1.01–1.02), P < 0.01 were associated with increased severity of RLS.
Conclusions
Our findings demonstrated that RLS is common in Taiwanese dialysis patients. Clinicians should have a high suspicion for the presence of RLS symptoms in patients with ESRD, especially those with type 2 diabetes, anemia, low serum iron status and long duration of dialysis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Simultaneous enhancement of out-coupling efficiency, internal quantum efficiency, and color purity in thermally activated delayed fluorescence (TADF) emitters is highly desired for the practical ...application of these materials. We designed and synthesized two isomeric TADF emitters, 2DPyM-mDTC and 3DPyM-pDTC, based on di(pyridinyl)methanone (DPyM) cores as the new electron-accepting units and di(tert-butyl)carbazole (DTC) as the electron-donating units. 3DPyM-pDTC, which is structurally nearly planar with a very small ΔE ST, shows higher color purity, horizontal ratio, and quantum yield than 2DPyM-mDTC, which has a more flexible structure. An electroluminescence device based on 3DPyM-pDTC as the dopant emitter can reach an extremely high external quantum efficiency of 31.9% with a pure blue emission. This work also demonstrates a way to design materials with a high portion of horizontal molecular orientation to realize a highly efficient pure-blue device based on TADF emitters.
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IJS, KILJ, NUK, PNG, UL, UM
Four 2-(styryl)triphenylene derivatives (TSs) were synthesized for deep-blue dopant materials. By using a pyrene-containing compound, DMPPP, as the host, the TS-doped devices exhibited significant ...delayed fluorescence via triplet-triplet annihilation, providing the highest quantum efficiency of 10.2% and a current efficiency of 12.3 cd A(-1).
Metastasis is the predominant cause of death in breast cancer patients. Several lines of evidence have shown that microRNAs (miRs) can have an important role in cancer metastasis. Using isogenic ...pairs of low and high metastatic lines derived from a human breast cancer line, we have identified miR-149 to be a suppressor of breast cancer cell invasion and metastasis. We also identified GIT1 (G-protein-coupled receptor kinase-interacting protein 1) as a direct target of miR-149. Knockdown of GIT1 reduced migration/invasion and metastasis of highly invasive cells. Re-expression of GIT1 significantly rescued miR-149-mediated inhibition of cell migration/invasion and metastasis. Expression of miR-149 impaired fibronectin-induced focal adhesion formation and reduced phosphorylation of focal adhesion kinase and paxillin, which could be restored by re-expression of GIT1. Inhibition of GIT1 led to enhanced protein degradation of paxillin and α5β1 integrin via proteasome and lysosome pathways, respectively. Moreover, we found that GIT1 depletion in metastatic breast cancer cells greatly reduced α5β1-integrin-mediated cell adhesion to fibronectin and collagen. Low level of miR-149 and high level of GIT1 was significantly associated with advanced stages of breast cancer, as well as with lymph node metastasis. We conclude that miR-149 suppresses breast cancer cell migration/invasion and metastasis by targeting GIT1, suggesting potential applications of the miR-149-GIT1 pathway in clinical diagnosis and therapeutics.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Pulsed radiofrequency (PRF) has been widely used to treat chronic pain, but the effectiveness and mechanisms in preventing early neuropathic pain have not been well explored. Even fewer ...knowledge is available in its impact on glia‐mediated nociceptive sensitization. This study aims to elucidate the modulation of PRF on nerve injury‐induced pain development and activation of spinal mitogen‐activated protein kinases (MAPKs).
Methods
In a rat spinal nerve ligation (SNL) model, a low‐volt PRF treatment was applied to the L5 dorsal root ganglion after nerve injury. Nociceptive behaviours were measured by von Frey and heat withdrawal tests at multiple time points. MAPK activations, including p‐ERK and p‐p38, as well as TNF‐α level in the spinal dorsal horn were assessed and the cell types that expressed MAPK activation were identified by double immunofluorescence staining.
Results
We found that SNL promptly induced neuropathic pain in the affected hind limb for over 1 week as well as increased p‐ERK and p‐p38 in the spinal dorsal horn. PRF significantly attenuated SNL‐induced mechanical allodynia and thermal hyperalgesia for 5–7 days. PRF also inhibited ERK and p38 activations, which were found majorly located within neurons and microglia, respectively. Besides, PRF significantly suppressed expression of TNF‐α in the spinal dorsal horn throughout the course.
Conclusions
Low‐volt PRF significantly ameliorated SNL‐induced acute pain. Inferentially, PRF may inhibit spinal sensitization by down‐regulating spinal MAPK activations and activation‐mediated cytokine release. We demonstrated that early PRF treatment in acute nerve injury helps to ameliorate neuropathic pain development.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
We report on the first global QCD analysis of the quark transversity distributions in the nucleon from semi-inclusive deep-inelastic scattering (SIDIS), using a new Monte Carlo method based on nested ...sampling and constraints on the isovector tensor charge g_{T} from lattice QCD. A simultaneous fit to the available SIDIS Collins asymmetry data is compatible with g_{T} values extracted from a comprehensive reanalysis of existing lattice simulations, in contrast to previous analyses, which found significantly smaller g_{T} values. The contributions to the nucleon tensor charge from u and d quarks are found to be δu=0.3(2) and δd=-0.7(2) at a scale Q^{2}=2 GeV^{2}.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
Objective
We investigated the risk of dementia in patients with type 2 diabetes with or without prior hypoglycaemic episodes.
Subjects and Setting
One million subjects randomly selected from the ...National Health Insurance Research Database, Taiwan.
Results
A total of 15 404 diabetic subjects without prior dementia and a mean age of 64.2 years were enrolled in the study. About 2% (n = 289) of participants had at least one episode of hypoglycaemia in a 3‐year period; these subjects were older and more likely to be women and also had higher rates of insulin use and comorbidities compared to those without hypoglycaemia. During a total of 7 years of follow‐up (mean and median follow‐up, 3.8 and 4.8 years, respectively), 1106 patients with diabetes (7.2%) developed dementia. The incidence rate of dementia was higher in diabetic subjects with 29.9 per 1000 person‐years (95% CI 22.1–39.2) compared to those without 11.1 per 1000 person‐years (95% CI 10.3–11.8) hypoglycaemic episodes. The crude rate ratio (RR) and age‐ and gender‐adjusted RR values for dementia were 2.76 (95% CI 2.06–3.70, P < 0.001) and 1.60 (95% CI 1.19–2.14, P = 0.002), respectively, in diabetic subjects with hypoglycaemia compared to those without hypoglycaemia. Results of Cox proportional hazards analysis revealed that hypoglycaemia, older age, female gender and insulin use were independent predictors of dementia.
Conclusion
Adult diabetic patients with prior hypoglycaemia had a significantly increased risk of dementia. The influence of hypoglycaemic episodes on brain function warrants further investigation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background and purpose
Earlier studies suggested an association between idiopathic restless legs syndrome (RLS) and cardiovascular diseases. However, the risk of cardiovascular events in patients ...with secondary RLS due to end‐stage renal disease (ESRD) is unclear. Our aim was to examine whether ESRD patients with RLS had an increased risk of cardio/cerebrovascular events and mortality.
Methods
In all, 1093 ESRD patients were recruited between 2009 and 2010. The diagnosis and severity of RLS were assessed in a face‐to‐face interview. The occurrence of cardio/cerebrovascular events and death were confirmed by medical record review. The association between RLS and the outcomes of interest was examined using an adjusted multivariate Cox regression model.
Results
After a mean follow‐up period of 3.7 ± 0.8 years, ESRD patients with RLS had a significantly higher risk of developing cardiovascular events and strokes adjusted hazard ratio (aHR) 2.82, 95% confidence interval (CI) 2.02–4.11, and aHR 2.41, 95% CI 1.55–3.75, respectively compared with patients without RLS. Increasing RLS severity was associated with an increasing likelihood of cardiovascular events mild RLS severity, aHR 1.71 (95% CI 1.02–2.87); moderate, 2.79 (1.64–4.66); severe, 2.85 (1.99–4.46) and strokes mild, 1.89 (0.87–4.16); moderate, 2.42 (1.50–3.90); severe, 2.64 (1.49–4.91) in a dose‐dependent manner. RLS also increased the risk of total mortality in patients with ESRD aHR 1.53 (95% CI 1.07–2.18), P = 0.02; this association attenuated slightly after stratification by individual RLS severity category mild RLS severity, aHR 1.44 (95% CI 0.78–2.67); moderate, 1.49 (0.98–2.55); severe, 2.03 (0.93–4.45).
Conclusions
ESRD patients with RLS demonstrated an increased likelihood of cardio/cerebrovascular events and mortality.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Use of polysomnography (PSG) is the gold standard of diagnosis and measurement of treatment effectiveness for paediatric obstructive sleep apnoea (OSA). Although adenotonsillectomy (T&A) ...is effective in diminishing the apnoea–hypopnoea index (AHI), a meta‐analysis of postoperative changes for all other PSG parameters and outcome comparisons between obese and non‐obese children following T&A have never been conducted.
Objective of review
To comprehensively review polysomnographic findings after surgery for obese and non‐obese children with OSA.
Search strategy
Study protocol was registered on PROSPERO (CRD42013004737). Two authors independently searched databases including PubMed, MEDLINE, EMBASE and Cochrane Review from January 1997 to July 2014. The keywords used included the following: sleep apnea, OSA, sleep apnea syndromes, tonsillectomy, adenoidectomy, infant, child, adolescent, and Humans.
Evaluation method
A comprehensive systematic review and meta‐analysis for literature for OSA children treated by T&A with polysomnography data. Random‐effects model was applied to determine postoperative sleep parameter changes and the surgical success rate between obese and non‐obese groups. The quality of studies was assessed using the Newcastle–Ottawa Scale.
Results
In total, 51 studies with 3413 subjects were enrolled. After surgery, sleep architecture was altered by a significant decrease in sleep stage 1, and an increase in slow‐wave sleep and the rapid eye movement stage, and enhanced sleep efficiency. The mean difference between pre‐ and postoperative was a significant reduction of 12.4 event/h in AHI, along with a reduction of obstructive index, hypopnoea index, central index and arousal index. Mean and minimum oxygen saturation increased significantly after surgery. The overall success rate was 51% for postoperative AHI <1 (obese versus non‐obese versus combined, 34% versus 49% versus 56%), and 81% for AHI <5 (obese versus non‐obese versus combined, 61% versus 87% versus 84%). Meta‐regression analyses demonstrate that postoperative AHI was positively correlated with AHI and body mass index z score before surgery.
Conclusions
Meta‐analysis of current literature shows T&A offers prominent improvement in a variety of sleep parameters. Improvements in non‐obese children exceeded those for obese children. Postoperative residual OSA remained in roughly half of the children, especially those with severe disease and obesity, making additional treatment strategies and/or long‐term follow‐up highly desirable.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The particulate methane monooxygenase (pMMO) is the first enzyme in the C1 metabolic pathway in methanotrophic bacteria. As this enzyme converts methane into methanol efficiently near room ...temperature, it has become the paradigm for developing an understanding of this difficult C1 chemistry. pMMO is a membrane-bound protein with three subunits (PmoB, PmoA, and PmoC) and 12–14 coppers distributed among different sites. X-ray crystal structures that have revealed only three mononuclear coppers at three sites have neither disclosed the location of the active site nor the catalytic mechanism of the enzyme. Here we report a cyro-EM structure of holo-pMMO from Methylococcus capsulatus (Bath) at 2.5 Å, and develop quantitative electrostatic-potential profiling to scrutinize the nonprotein densities for signatures of the copper cofactors. Our results confirm a mononuclear CuI at the A site, resolve two CuIs at the B site, and uncover additional CuI clusters at the PmoA/PmoC interface within the membrane (D site) and in the water-exposed C-terminal subdomain of the PmoB (E clusters). These findings complete the minimal set of copper factors required for catalytic turnover of pMMO, offering a glimpse of the catalytic machinery for methane oxidation according to the chemical principles underlying the mechanism proposed earlier.
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IJS, KILJ, NUK, PNG, UL, UM
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