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.
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.
Background and purpose
Recent genome‐wide association studies have shown associations between multiple genetic variants and primary restless legs syndrome (RLS). Their roles in end stage renal ...disease (ESRD) related secondary RLS are not clear and studies in Asian populations are scarce. The association between candidate genetic variants and uremic RLS was investigated in a large cohort of Taiwanese dialysis patients.
Methods
Sixteen RLS‐related genetic variants at six loci, including MEIS1, BTBD9, MAP2K5/SKOR1, PTPRD, TOX3/BC034767 and the intergenic region of chromosome 2p14, in a total of 993 ESRD patients (259 subjects with and 734 subjects without RLS) were genotyped using TaqMan® genotyping assays. Multivariate logistic regression analysis was used to test for associations between the genotypes and RLS in ESRD. Power calculations were completed using the CATs Genetic Power Calculator with settings of a multiplicative genetic model.
Results
A modest association between the PTPRD variant rs4626664 and uremic RLS (odds ratio 1.52, 95% CI 1.03–2.23, P = 0.03) and a trend that TOX3/BC034767 variant rs3104767 may associate with the occurrence of RLS were observed in our dialysis population (odds ratio 1.74, 95% CI 0.97–3.11, P = 0.06). No associations between other genetic variants and risk and severity of RLS were observed in our ESRD cohort.
Conclusions
The genetic variants of primary RLS candidate genes did not play a major role in our uremic RLS populations. The ethnic difference and heterogeneous etiologies underlying renal failure may partly explain the minor genetic contribution to uremic RLS in our populations. Further studies for other ethnicities will be of worth.
Cerebral infarction in tuberculous meningitis is a major risk factor for permanent disability. This study assessed the clinical presentation of tuberculous meningitis and risks factors for cerebral ...infarction.
Thirty-eight adult patients with tuberculous meningitis were studied between 2002 and 2006. Clinical, radiological, and laboratory data of patients with cerebral infarction were compared with those of patients without cerebral infarction. Patients with cerebral infarction were significantly older (65.1 vs 52.1years), had higher risk assessment scores (3.7 vs 2.2), and more often had basal meningeal enhancement on imaging (92.3% vs 60.0%), mild to moderate sequelae (69.2% vs 4%), an overall poor brain outcome (69.2% vs 8%), aspirin prescription (84% vs 8%), and neurosurgical intervention for hydrocephalus (54.0% vs 16.0%). Cerebral infarction patients were also more likely to have experienced doctor-related delays in antituberculosis (61.5% vs 36%) and corticosteroid (61.5% vs 32%) therapy.
The Framingham risk score would be an option for tuberculous meningitis patients to access cerebral infarction risk. Contrast-enhanced brain imaging is helpful for exploring basal meningeal enhancement, in order to obtain an early diagnosis. Antituberculosis, corticosteroid, and aspirin therapies should be started immediately when tuberculous meningitis is suspected.
L’infarctus cérébral dans la méningite tuberculeuse est un facteur de risque majeur d’incapacité permanente. Cette étude a évalué la présentation clinique de la méningite tuberculeuse et les facteurs de risque d’infarctus cérébral.
Les cas de trente-huit patients adultes atteints de méningite tuberculeuse ont été étudiés entre 2002 et 2006. Les données de laboratoire et celles cliniques et radiologiques des patients avec un infarctus cérébral ont été comparées à celles des patients sans infarctus cérébral. Les patients avec un infarctus cérébral étaient significativement plus âgés (65,1 contre 52,1 années), avaient des scores plus élevés dans l’évaluation des risques (3,7 vs 2,2), avaient le plus souvent vu une amélioration méningée fondamentale sur l’imagerie (92,3 % vs 60,0 %), des séquelles de légères à modérées (69,2 % contre 4 %), un résultat global médiocre du cerveau (69,2 % contre 8 %), une prescription d’aspirine (84 % contre 8 %) et une intervention neurochirurgicale pour hydrocéphalie (54,0 % contre 16,0 %). Les patients ayant subi un infarctus cérébral étaient également plus susceptibles de profiter en retard d’une thérapie antituberculeuse (61,5 % contre 36 %) et corticostéroïde (61,5 % contre 32 %) décidée par des médecins expérimentés.
Le score de risque de Framingham serait une option pour les patients atteints de méningite tuberculeuse pour accéder au risque d’infarctus cérébral. Le renforcement du contraste en imagerie cérébrale est utile pour explorer l’amélioration méningée fondamentale et ce, afin d’obtenir un diagnostic précoce. Des thérapies antituberculeuses, à base de corticoïdes ou d’aspirine, doivent être lancées dès qu’une méningite tuberculeuse est suspectée.
Polyphenolic compounds present in green tea, particularly catechins, are known to have strong anti-influenza activity. The goal of this study was to determine whether green tea by-products could ...function as an alternative to common antivirals in animals compared to original green tea. Inhibition of viral cytopathic effects ascertained by neutral red dye uptake was examined with 50% effective (virus-inhibitory) concentrations (EC50) determined. Against the H1N1 virus A/NWS/33, we found the anti-influenza activity of green tea by-products (EC50 = 6.36 µg/mL) to be equivalent to that of original green tea (EC50 = 6.72 µg/mL). The anti-influenza activity of green tea by-products was further examined in mouse and chicken influenza infection models. In mice, oral administration of green tea by-products reduced viral titers in the lungs in the early phase of infection, but they could not protect these animals from disease and death. In contrast, therapeutic administration of green tea by-products via feed or water supplement resulted in a dose-dependent significant antiviral effect in chickens, with a dose of 10 g/kg of feed being the most effective (P < 0.001). We also demonstrated that unidentified hexane-soluble fractions of green tea by-products possessed strong anti-influenza activity, in addition to ethyl acetate-soluble fractions, including catechins. This study revealed green tea by-product extracts to be a promising novel antiviral resource for animals.
Cooperative spectrum sharing (CSS) is a joint spectrum access technique that involves collaboration between primary user (PU) and secondary user (SU) systems. An instance of CSS occurs when the SU ...transmitter acts as a relay for the PU system. In forwarding the PU signal, the SU transmitter deliberately superimposes the signal intended for the SU receiver. This process unfortunately causes mutual interferences at both PU and SU receivers. Achievable rates for both systems are typically analyzed by assuming Gaussian signals and interferences. Unlike most of previous work, this paper studies the use of practical digital modulation schemes in CSS. The novelty of the proposed CSS approach lies on the smart alignment and superimposition of the SU's pulse amplitude modulated signal to the PU's phase-shift keying signal. It is shown that the SU signal does not interfere with the PU signal, it actually improves the PU signal strength. This paper then focuses on deriving the approximated theoretical transmission rates for both the PU and SU. Interestingly, the analysis shows superior transmission rates for both systems, compared to that achieved by conventional signal superimposition approaches. Simulation results then confirm the matching with the analytical results and validate the performance advantages of the proposed CSS approach.
This paper studies the exploitation of the modulation-based dimension in cognitive radio systems to perform cooperative spectrum sharing (CSS). Unlike conventional opportunistic spectrum sharing ...techniques where a secondary user (SU) system attempts to utilize the spectrum hole in either time, frequency, or spatial dimension created by the primary user (PU) system, this study focuses on finding accessible spectrum spaces created by the structure of modulation constellations. In this novel CSS scheme, by taking advantage of the knowledge on the PU's modulation scheme, the SU superimposes its own modulated signal on the PU's signal. We examine two CSS scenarios: 1) phase-shift-keying (PSK) is used at both the PU and SU and 2) PSK is used at the PU while pulse-amplitude modulation is used at the SU. Interestingly, the proposed superposition approach in CSS Scenario 2 enables a CSS mechanism without either impairing the performance of the primary receiver or requiring a change in its demodulation rule. At the same time, a much better symbol-error-rate (SER) performance is achievable for the SU's receiver in Scenario 2 than in Scenario 1. Theoretical SER performances of both the PU and SU are then thoroughly analyzed and confirmed by numerical simulations.
High-risk human papillomavirus (HPV) is a major risk factor for oral and pharyngeal cancers (OPCs), yet the detailed mechanisms by which HPV promotes OPCs are not understood. Forkhead box M1B ...(FoxM1B) is an oncogene essential for cell cycle progression and tumorigenesis, and it is aberrantly overexpressed in many tumors. We previously showed that FoxM1B was the putative target of an epithelial-specific transcription factor, Grainyhead-like 2 (GRHL2). In the current study, we demonstrate that HPV type 16 (HPV-16) E6 induces FoxM1B in human oral keratinocytes (HOKs) and tonsillar epithelial cells (TECs) in part through GRHL2. FoxM1B was barely detectable in cultured normal human oral keratinocytes (NHOKs) and progressively increased in immortalized HOKs harboring HPV-16 genome (HOK-16B) and tumorigenic HOK-16B/BaP-T cells. Retroviral expression of HPV-16 E6 and/or E7 in NHOKs, TECs, and hypopharyngeal carcinoma cells (FaDu) revealed induction of FoxM1B and GRHL2 by the E6 protein but not E7. Both GRHL2 and FoxM1B were strongly induced in the epidermis of HPV-16 E6 transgenic mice and HPV+ oral squamous cell carcinomas. Ectopic expression of FoxM1B led to acquisition of transformed phenotype in HOK-16B cells. Loss of FoxM1B by lentiviral short hairpin RNA vector or chemical inhibitor led to elimination of tumorigenic characteristics of HOK-16B/BaP-T cells. Luciferase reporter assay revealed that GRHL2 directly bound and regulated the FoxM1B gene promoter activity. Using epithelial-specific Grhl2 conditional knockout mice, we exposed wild-type (WT) and Grhl2 KO mice to 4-nitroquinolin 1-oxide (4-NQO), which led to induction of FoxM1B in the tongue tissues and rampant oral tumor development in the WT mice. However, 4-NQO exposure failed to induce tongue tumors or induction of FoxM1B expression in Grhl2 KO mice. Collectively, these results indicate that HPV-16 induces FoxM1B in part through GRHL2 transcriptional activity and that elevated FoxM1B level is required for oropharyngeal cancer development.
A lectin gene from the Tiger Milk Mushroom Lignosus rhinocerus TM02® was successfully cloned and expressed via vector pET28a in Escherichia coli BL21(DE3). The recombinant lectin, Rhinocelectin, with ...a predicted molecular mass of 22.8 kDa, was overexpressed in water‐soluble form without signal peptide and purified via native affinity chromatography Ni‐NTA agarose. Blast protein analysis indicated the lectin to be homologous to jacalin‐related plant lectin. In its native form, Rhinocelectin exists as a homo‐tetramer predicted with four chains of identical proteins consisting of 11 beta‐sheet structures with only one alpha‐helix structure. The antiproliferative activity of the Rhinocelectin against human cancer cell lines was concentration dependent and selective. The IC50 values against triple negative breast cancer cell lines MDA‐MB‐231 and breast cancer MCF‐7 are 36.52 ± 13.55 μg mL−1 and 53.11 ± 22.30 μg mL−1, respectively. Rhinocelectin is only mildly cytotoxic against the corresponding human nontumorigenic breast cell line 184B5 with IC50 value at 142.19 ± 36.34 μg mL−1. The IC50 against human lung cancer cell line A549 cells is 46.14 ± 7.42 μg mL−1 while against nontumorigenic lung cell line NL20 is 41.33 ± 7.43 μg mL−1. The standard anticancer drug, Doxorubicin exhibited IC50 values mostly below 1 μg mL−1 for the cell lines tested. Flow cytometry analysis showed the treated breast cancer cells were arrested at G0/G1 phase and apoptosis induced. Rhinocelectin agglutinated rat and rabbit erythrocytes at a minimal concentration of 3.125 μg mL−1 and 6.250 μg mL−1, respectively.
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