A model selection criterion for clustered survival analysis with informative cluster size.

We propose a model selection criterion for correlated survival data when the cluster size is informative to the outcome. This approach, called Resampling Cluster Survival Information Criterion (RCSIC), uses the Cox proportional hazards model that is weighted with the inverse of the cluster size. The RCSIC based on the within-cluster resampling idea takes into account the possible variability of the within-cluster subsampling and the possible informativeness of cluster sizes. The RCSIC allows for easy execution for the within-cluster resampling idea without a large number of resamples of the data. In contrast with the traditional model selection method in survival analysis, the RCSIC has an additional penalization for the within-cluster subsampling variability. Our simulations show the satisfactory results where the RCSIC provides a more robust power for variable selection in terms of clustered survival analysis, regardless of whether informative cluster size exists or not. Applying the RCSIC method to a periodontal disease studies, we identify the tooth loss in patients associated with the risk factors, Age, Filled Tooth, Molar, Crown, Decayed Tooth, and Smoking Status, respectively.

Effects of a dynamic combined training on impulse response for middle-aged and elderly patients with osteoporosis and knee osteoarthritis: a randomized control trial.

Dynamic combined training is a crucial component in treating musculoskeletal conditions to increase muscle strength and improve functional ability. This randomized control trial aimed to examine the effect of dynamic combined training on muscle strength and contractile rate of force development (RFD) in patients with osteoporosis (OP) and knee osteoarthritis (KOA). 58 participants with OP or KOA were randomly assigned to a control group (CG) (CGOP, n = 12; CGKOA, n = 15) or training group (TG) (TGOP, n = 14; TGKOA, n = 17). The training group participated in a 12-week, three-days-per-week supervised program consisting of stretching and warm-up exercises (10 min), hydraulic resistance training (40 min), and cool-down and relaxation exercises (10 min). All participants were evaluated at baseline and post-training. The maximal voluntary contraction (MVC) and contractile RFD at 0-200 ms increased significantly in middle-aged and older patients with OP. As for KOA, the dynamic combined training program was effective in improving the muscle strength. The maximal voluntary contraction (MVC) and contractile RFD at 0-200 ms increased significantly (by 29.22%, P = .000 and 27.25%, P = .019, respectively) in middle-aged and older patients with OP. In the KOA group, MVC and contractile RFD improved but did not reach statistical significance. The dynamic combined training program is effective for health promotion in older adults with OP or KOA.

An Efficient and Geometric-Distortion-Free Binary Robust Local Feature.

An efficient and geometric-distortion-free approach, namely the fast binary robust local feature (FBRLF), is proposed. The FBRLF searches the stable features from an image with the proposed multiscale adaptive and generic corner detection based on the accelerated segment test (MAGAST) to yield an optimum threshold value based on adaptive and generic corner detection based on the accelerated segment test (AGAST). To overcome the problem of image noise, the Gaussian template is applied, which is efficiently boosted by the adoption of an integral image. The feature matching is conducted by incorporating the voting mechanism and lookup table method to achieve a high accuracy with low computational complexity. The experimental results clearly demonstrate the superiority of the proposed method compared with the former schemes regarding local stable feature performance and processing efficiency.

Corilagin Reduces the Frequency of Seizures and Improves Cognitive Function in a Rat Model of Chronic Epilepsy.

BACKGROUND Worldwide, epilepsy is an important chronic neurological condition. The aim of this study was to evaluate the effects of corilagin, an ellagitannin extracted from medicinal plants, on the frequency of seizures and cognitive function in a rat model of chronic epilepsy. MATERIAL AND METHODS Chronic epilepsy was induced in male Wistar rats by intraperitoneal (IP) injection of pentylenetetrazol (PTZ) for 36 days. Corilagin, 10 mg/kg and 20 mg/kg, was injected IP into treated rats, 24 days before the start of PTZ treatment, until the end of the protocol. The effects of corilagin were assessed by the pattern of epileptic seizures; cognitive function was assessed using the Morris water maze (MWM) navigation test. The mechanism of action of corilagin was investigated by measuring cytokine levels and oxidative stress parameters, including reactive oxygen species (ROS) production, and carbonic anhydrase inhibitory (CAI) activity. Histological analysis of fixed brain tissue sections included cresyl violet acetate staining (Nissl staining) for Nissl substance in the neuronal cytoplasm. RESULTS The corilagin-treated rats, compared with the control group, showed a significantly lower rate of epileptic events, improved cognitive function, reduced level of cytokines, reduced ROS production reduced CAI activity in the brain tissues (P<0.01). Histology of the rat brain tissues study showed that corilagin treatment maintained the neuronal cellular structure and number of surviving cells compared with the control group of rats. CONCLUSIONS The findings of this study showed that corilagin reduced the frequency of seizures and improved the cognitive function in a rat model of chronic epilepsy.

Incidence of Augmentation in Primary Restless Legs Syndrome Patients May Not Be That High: Evidence From A Systematic Review and Meta-Analysis.

Augmentation is a common complication of primary restless legs syndrome (RLS) during treatment; however, its incidence rate remains unclear.The aim of this study is investigate the rate of augmentation during RLS treatment.We searched 6 databases, including PubMed, OVID, Embase, Wiley citations, Web of Science research platform (including SciELO Citation Index, Medline, KCI Korean Journal Database, the Web of Science™ Core Collection), and the Cochrane library, and screened the reference lists of the included trials and recently published reviews.Randomized controlled trials and observational studies that reported augmentation events during RLS treatment.Primary RLS patients older than 18 years.No restrictions regarding intervention types were applied.Three investigators independently extracted and pooled the data to analyze the augmentation rate of the total sample and of patient subgroups with different interventions, treatment durations and drug regimens and different geographic origins. Fixed-effects or random-effects model was used for pooled analysis.A total of 60 studies involving 11,543 participants suggested an overall augmentation rate of 5.6% (95% confidence intervals (CI), 4.0-7.7). The augmentation incidence was 6.1% (95% CI, 4.1-9.1) for long-term treatment and 3.3% (95% CI, 1.4-7.3) for short-term treatment. In addition, 27.1% (95% CI, 12.3-49.5) of the levodopa-treated patients, 6.0% (95% CI, 4.1-8.8) of the patients treated with dopamine agonists, and 0.9% (95% CI, 0.2-3.3) of the patients taking pregabalin or gabapentin developed augmentation. Augmentation occurred in 7.2% (95% CI, 5.0-10.3) of the patients taking immediate-release drugs and in 1.7% (95% CI, 0.6-5.0) of the patients taking transdermal application.The main limitations are that the augmentation rates were not evaluated according to drug dosage, gender, and age and symptom severity.Approximately 5 to 6 in 100 RLS patients developed augmentation during treatment.

Does functional fitness decline in accordance with our expectation? - a pilot study in healthy female.

BACKGROUND: Aging may cause various functional abilities gradually deteriorate. With changes in social forms, the trend of functional fitness decline will change accordingly. Therefore, this study endeavored to identify the trends in functional fitness decline by comparing the differences in the functional fitness of females in various age groups. METHODS: Thirty six healthy females were divided into 3 age groups: young healthy females (20 to 30 y); middle-age (45 to 55 y); and older (65 to 75 y). Functional fitness test battery included flexibility, muscle strength/endurance, aerobic endurance, balance and agility. RESULTS: The performance in the elderly group was significantly worse (P < .05) in all the tests, whereas the muscle strength and endurance, as well as aerobic endurance for the middle-age group showed significantly lower than young groups (P < .05). CONCLUSIONS: The reduction in lower extremity muscle strength occurs in the middle-age group. We recommend that middle-age women be conscious of the reduction in their lower extremity muscle strength and conduct advanced preparations for future aging.

Clinical significance of tumor necrosis factor-α inhibitors in the treatment of sciatica: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Currently, no satisfactory treatment is available for sciatica caused by herniated discs and/or spinal stenosis. The objective of this study is to assess the value of tumor necrosis factor (TNF)-α inhibitors in the treatment of sciatica. METHODS: Without language restrictions, we searched PubMed, OVID, EMBASE, the Web of Science, the Clinical Trials Registers, the Cochrane Central Register of Controlled Trials and the China Academic Library and Information System. We then performed a systematic review and meta-analysis on the enrolled trials that met the inclusion criteria. RESULTS: Nine prospective randomized controlled trials (RCTs) and two before-after controlled trials involving 531 patients met our inclusion criteria and were included in this study. Our systematic assessment and meta-analysis demonstrated that in terms of the natural course of the disease, compared with the control condition, TNF-α inhibitors neither significantly relieved lower back and leg pain (both p > 0.05) nor enhanced the proportion of patients who felt overall satisfaction (global perceived effect (satisfaction)) or were able to return to work (return to work) (combined endpoint; p > 0.05) at the short-term, medium-term and long-term follow-ups. In addition, compared with the control condition, TNF-α inhibitors could reduce the risk ratio (RR) of discectomy or radicular block (combined endpoint; RR = 0.51, 95% CI 0.26 to 1.00, p = 0.049) at medium-term follow-up, but did not decrease RR at the short-term (RR = 0.64, 95% CI 0.17 to 2.40, p = 0.508) and long-term follow-ups (RR = 0.64, 95% CI 0.40 to 1.03, p = 0.065). CONCLUSION: The currently available evidence demonstrated that other than reducing the RR of discectomy or radicular block (combined endpoint) at medium-term follow-up, TNF-α inhibitors showed limited clinical value in the treatment of sciatica caused by herniated discs and/or spinal stenosis.

K33-Linked Polyubiquitination of Coronin 7 by Cul3-KLHL20 Ubiquitin E3 Ligase Regulates Protein Trafficking.

Ubiquitin chains are formed as structurally distinct polymers via different linkages, and several chain types including K33-linkage remain uncharacterized. Here, we describe a role for K33-polyubiquitination in protein trafficking. We show that the Cullin 3 (Cul3) substrate adaptor KLHL20 is localized to the trans-Golgi network (TGN) and is important for post-Golgi trafficking by promoting the biogenesis of TGN-derived transport carriers. The Cul3-KLHL20 ubiquitin E3 ligase catalyzes a nondegradable, K33-linked polyubiquitination on coronin 7 (Crn7), which facilitates Crn7 targeting to TGN through a ubiquitin-dependent interaction with Eps15. Blockage of K33-chain formation, Crn7 ubiquitination, or disruption of Crn7-Eps15 interaction impairs TGN-pool F-actin assembly, a process essential for generating transport carriers. Enforced targeting of Crn7 to TGN bypasses the requirement of K33-ubiquitination for TGN-pool F-actin assembly and post-Golgi trafficking. Our study reveals a role of KLHL20-mediated K33-ubiquitination of Crn7 in post-Golgi transport and identifies a cellular recognition mechanism for this ubiquitin chain type.

The efficacy and safety of novel oral anticoagulants for the preventive treatment in atrial fibrillation patients: a systematic review and meta-analysis.

BACKGROUND: Novel oral anticoagulants, including direct factor Xa inhibitors and direct factor IIa inhibitors, have been used to prevent stroke in patients with atrial fibrillation (AF) for a decade. In this study, the efficacy and safety of the novel oral anticoagulants were assessed in AF patients. METHODS: No language restrictions were applied. Study selection and data extraction were carried out by searching PubMed, EMBASE, OVID, the BIOSIS, the Web of Science, Clinical Trials Registers, Cochrane Central Register of Controlled Trials and the China Academic Library and Information System. Each database was searched from its inception date to June 2013. Using odds ratio (OR) as an indicator, we systematically evaluated the primary efficacy endpoints and safety endpoints, as well as 10 secondary endpoints. RESULT: Compared to the control drugs, the novel oral anticoagulants showed an OR decreased by 26% (OR: 0.74, 95% confidence interval (CI): 0.62-0.88) for stroke or systemic embolism, decreased by 24% (OR: 0.76, 95% CI: 0.64-0.90) for major bleeding, decreased by 10% (OR: 0.90, 95% CI: 0.84-0.95) for death from any cause, decreased by 27% for disabling or fatal stroke (OR: 0.73, 95% CI: 0.54-0.97), decreased by 31% (OR: 0.69, 95% CI: 0.60-0.8) for fatal bleeding, and decreased by 8% (OR: 0.92, 95% CI: 0.88-0.95) for serious adverse events. However, there was no significant difference in acute myocardial infarction, systemic embolism, major bleeding or clinically relevant non-major, all bleeding events, all adverse events and liver function disorder, between the novel oral anticoagulants and control drugs (p > 0.05). CONCLUSIONS: Compared to the control drugs, the novel oral anticoagulants showed higher efficiency and safety in patients with AF, as evidenced by their superior performance not only in reducing the risk of stroke or systemic embolism with a lower risk of major bleeding but also in decreasing the incidence of death from any cause, disabling or fatal stroke, serious adverse events and fatal bleeding.

[Effects of injecting heparin into the center of hematoma on peri-hematoma edema and hematoma volume in pigs with intracerebral hemorrhage].

OBJECTIVE: To investigate the safety and effect of injecting heparin into hematoma on peri-hematoma edema and hematoma volume in pigs with intracerebral hemorrhage (ICH). METHODS: Thirteen sucking pigs were divided randomly into two groups: hemorrhage group, in which 2.5 ml arterial blood was injected into the right frontal lobe and heparin group, in which 0.2 ml of heparin was injected into the hematoma produced by the injection of 2.3 ml of blood into the similar site. The hematoma volume and peri-hematoma edema were determined by the sequences of T2* weighted image (T2*WI), fluid-attenuated inversion- recovery (FLAIR) image and diffusion weighted image (DWI) by 1.5 T magnetic resonance image (MRI) from 30-60 minutes afterwards to 24 hours. The peri-hematoma apparent diffusion coefficient (ADC) was compared with that of contralateral hemisphere, and the corresponding histologic changes were studied. RESULTS: The average volume, shown by T2*WI at 24 hours, was significantly larger than that at 30-60 minutes after hematoma formation in hemorrhagic group [(5.29+/-0.98) cm3 vs. (3.09+/-0.38) cm3, P<0.01]. But there was no significant change in hematoma volume in hemorrhagic group from 30-60 minutes on to 24 hours [(2.21+/-0.28) cm3 vs. (2.33+/-0.30) cm3, P>0.05]. Both increased and decreased ADC were found around the hematoma in some animals of the heparin group compared with that of the contralateral hemisphere. On the other hand, in hemorrhagic group, only increased ADC could be found around the lesion, and there was no decreased ADC. CONCLUSION: Injection of heparin into an intracerebral hematoma leads to enlargement of the hematoma and more marked peri-lesion edema. On ADC maps, enlargement of hematoma is attributed to the edema around the lesion leading to injury to the brain tissue.

Factors governing the substitution of La3+ for Ca2+ and Mg2+ in metalloproteins: a DFT/CDM study.

Trivalent lanthanide cations are extensively being used in biochemical experiments to probe various dication-binding sites in proteins; however, the factors governing the binding specificity of lanthanide cations for these binding sites remain unclear. Hence, we have performed systematic studies to evaluate the interactions between La3+ and model Ca2+ - and Mg2+ -binding sites using density functional theory combined with continuum dielectric methods. The calculations reveal the key factors and corresponding physical bases favoring the substitution of trivalent lanthanides for divalent Ca2+ and Mg2+ in holoproteins. Replacing Ca2+ or Mg2+ with La3+ is facilitated by (1) minimizing the solvent exposure and the flexibility of the metal-binding cavity, (2) freeing both carboxylate oxygen atoms of Asp/Glu side chains in the metal-binding site so that they could bind bidentately to La3+, (3) maximizing the number of metal-bound carboxylate groups in buried sites, but minimizing the number of metal-bound carboxylate groups in solvent-exposed sites, and (4) including an Asn/Gln side chain for sites lined with four Asp/Glu side chains. In proteins bound to both Mg2+ and Ca2+, La3+ would prefer to replace Ca2+, as compared to Mg2+. A second Mg2+-binding site with a net positive charge would hamper the Mg2+ --> La3+ exchange, as compared to the respective mononuclear site, although the La3+ substitution of the first native metal is more favorable than the second one. The findings of this work are in accord with available experimental data.

Endoscopic hemostasis of a bleeding marginal ulcer: hemoclipping or dual therapy with epinephrine injection and heater probe thermocoagulation.

BACKGROUND AND AIMS: Endoscopic hemoclipping and dual therapy with epinephrine injection and heater probe thermocoagulation have been proven effective in the hemostasis of bleeding peptic ulcers. However, the hemostatic efficacy has not been investigated in bleeding marginal ulcers. The aim of this study is to investigate the hemostatic efficacy of endoscopic hemoclipping and dual therapy with epinephrine injection and heater probe thermocoagulation in bleeding marginal ulcers. METHODS: From November 1997 to July 2000, 50 patients with active marginal ulcer bleeding underwent either hemoclipping (20 patients) or dual therapy (30 patients) for hemostasis. The demographic data, clinicopathological characteristics, endoscopic findings, initial hemostatic rates, rebleeding rates, amount of blood transfusion, the need of surgery, and mortality rates were collected and analyzed. RESULTS: Marginal ulcers were located at the anastomotic site (64%), saddle portion (22%), efferent loop (10%), or at the afferent loop (4%). The bleeding stigmata were classified into spurting artery (32%), oozing vessel (38%), visible vessel (20%), and blood clot adhesion (10%). The overall therapeutic results in 50 patients were initial hemostasis (100%), rebleeding rate (22%), need for surgery (4%), and hospital mortality rate (4%). There was no significant difference in demographic data and clinicopathological characteristics between the two modes of treatments, whereas recurrent bleeding developed in 5% in the hemoclipping group and 33% in the dual therapy group. No complication related to the procedure occurred in either mode of therapy. The hospital mortality rates were 0 and 6.7%, respectively. CONCLUSION: Endoscopy is effective in achieving initial hemostasis from bleeding marginal ulcers. However, the rebleeding rate remains high and repeated endoscopy may be needed to arrest the hemorrhage.