Validity and test-retest reliability of a resistance training device for Smith machine back squat exercise.

This study evaluated the validity and test-retest reliability of a resistance training device Jueying (Beijing, China) for Smith machine back squat exercise. Twelve male participants completed two test sessions with an interval of one week. In each test session, participants completed 30%, 45%, 60%, and 75% of 1RM back squats on a Smith machine equipped with Jueying and a linear position transducer GymAware (Canberra, Australia), which measured the velocity and power during the movement simultaneously. Results showed that Jueying was both valid (Pearson correlation coefficient [r] = 0.896-0.999, effect size [ES] = 0.004-0.192) when compared with GymAware and consistent between two tests in terms of reliability (intraclass correlation coefficient [ICC] = 0.79-0.95) to assess speed and power within all exercises. The device could be applied to provide athletes and coaches with effective and reliable data in actual application.

Markerless vision-based functional movement screening movements evaluation with deep neural networks.

The functional movement screen (FMS) test is a seven-test battery used to assess fundamental movement abilities of individuals. It is commonly used to predict sports injuries but relies on clinical expertise and is not suitable for self-examination. This study presents an automatic FMS movement assessment framework using a multi-view deep neural network called MVDNN. The framework combines automatic skeleton extraction with manual feature selection to extract 3D trajectory features of human skeleton joints from two different directions. Three mainstream methods of time-series modeling are then used to learn high-level feature representation from skeleton sequences, and motion features from two views are fused to provide complementary information. Results of public FMS movements dataset demonstrate that our MVDNN outperforms current state-of-the-art methods with an average miF1 score of 0.857, maF1 score of 0.768, and Kappa score of 0.640 over ten runs.

A simple, flexible, and high-efficiency western blot analysis for age-related human induced neurons.

High-throughput western blot (WB) analysis can be used to obtain more consistent, comparable, and informative data from precious samples and materials with extremely limited availability, such as various age-related, subtype-specific human induced neurons (hiNs). In this study, p-toluenesulfonic acid (PTSA), an odorless tissue fixative, was used to inactivate horseradish peroxidase (HRP) and develop a high-throughput WB method. PTSA-treated blots demonstrated rapid and efficient HRP inactivation without detectable protein loss or epitope damage. With a brief PTSA treatment (1 min at room temperature [RT]) before every subsequent probing, 10 dopaminergic hiN proteins could be sequentially, sensitively, and specifically detected in the blot. The resulting WB data confirmed the age-associated and neuron-specific features of hiNs and revealed a significant reduction in two Parkinson's disease-associated proteins, UCHL1 and GAP43, in normal aging dopaminergic neurons. Overall, this study developed a unique and high-efficiency WB analysis method for capturing robust and useful data from limited, precious samples.

Functional movement screen dataset collected with two Azure Kinect depth sensors.

This paper presents a dataset for vision-based autonomous Functional Movement Screen (FMS) collected from 45 human subjects of different ages (18-59 years old) executing the following movements: deep squat, hurdle step, in-line lunge, shoulder mobility, active straight raise, trunk stability push-up and rotary stability. Specifically, shoulder mobility was performed only once by different subjects, while the other movements were repeated for three episodes each. Each episode was saved as one record and was annotated from 0 to 3 by three FMS experts. The main strength of our database is twofold. One is the multimodal data provided, including color images, depth images, quaternions, 3D human skeleton joints and 2D pixel trajectories of 32 joints. The other is the multiview data collected from the two synchronized Azure Kinect sensors in front of and on the side of the subjects. Finally, our dataset contains a total of 1812 recordings, with 3624 episodes. The size of the dataset is 190 GB. This dataset provides the opportunity for automatic action quality evaluation of FMS.

A novel DNA methylation-based model that effectively predicts prognosis in hepatocellular carcinoma.

PURPOSE: To build a novel predictive model for hepatocellular carcinoma (HCC) patients based on DNA methylation data. METHODS: Four independent DNA methylation datasets for HCC were used to screen for common differentially methylated genes (CDMGs). Gene Ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to explore the biological roles of CDMGs in HCC. Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) Cox analysis were performed to identify survival-related CDMGs (SR-CDMGs) and to build a predictive model. The importance of this model was assessed using Cox regression analysis, propensity score-matched (PSM) analysis and stratification analysis. A validation group from the Cancer Genome Atlas (TCGA) was constructed to further validate the model. RESULTS: Four SR-CDMGs were identified and used to build the predictive model. The risk score of this model was calculated as follows: risk score = (0.01489826 × methylation level of WDR69) + (0.15868618 × methylation level of HOXB4) + (0.16674959 × methylation level of CDKL2) + (0.16689301 × methylation level of HOXA10). Kaplan-Meier analysis demonstrated that patients in the low-risk group had a significantly longer overall survival (OS; log-rank P-value =0.00071). The Cox model multivariate analysis and PSM analysis identified the risk score as an independent prognostic factor (P<0.05). Stratified analysis results further confirmed this model performed well. By analyzing the validation group, the results of receiver operating characteristic (ROC) curve analysis and survival analysis further validated this model. CONCLUSION: Our DNA methylation-based prognosis predictive model is effective and reliable in predicting prognosis for patients with HCC.

The effects of autophagy on the replication of Nelson Bay orthoreovirus.

BACKGROUND: Nelson Bay orthoreovirus (NBV) was first isolated over 40 years ago from a fruit bat in Australia. Normally, NBV does not cause human diseases, but recently several NBV strains have been associated with human respiratory tract infections, thus attracting clinical attention. Autophagy, an evolutionarily conserved process in eukaryotic cells, degrades intracellular substrates, participates in multiple physiological processes, and maintains cellular homeostasis. In addition, autophagy is intimately involved in viral infection. METHODS: A new strain of NBV, isolated from a patient with a respiratory tract infection who returned to Japan from Bali, Indonesia, in 2007, was used in this study. NBV was rescued using a reverse genetics system involving cotransfection of BHK cells with 11 plasmids (pT7-L1 MB, pT7-L2 MB, pT7-L3 MB, pT7-M1 MB, pT7-M2 MB, pT7-M3 MB, pT7-S1 MB, pT7-S2 MB, pT7-S3 MB, pT7-S4 MB, and pcDNA3.1-T7), yielding NBV-MB. Recovered viruses were confirmed by immunofluorescence. The effect of NBV-MB on autophagy was evaluated by measuring the LC3-I/II proteins by immunoblot analysis after infection of BHK cells. Furthermore, after treatment with rapamycin (RAPA), 3-methyladenine (3-MA), chloroquine (CQ), or plasmid (GFP-LC3) transfection, the changes in expression of the LC3 gene and the amount of LC3-I/II protein were examined. In addition, variations in viral titer were assayed after treatment of BHK cells with drugs or after transfection with plasmids pCAGM3 and pCAGS3, which encode virus nonstructural proteins µNS and σNS, respectively. RESULTS: NBV-MB infection induced autophagy in host cells; however, the level of induction was dependent on viral replication. Induction of autophagy increased viral replication. By contrast, inhibiting autophagy suppressed NBV replication, albeit not significantly. The NBV-MB nonstructural protein µNS was involved in the induction of autophagy with viral infection. CONCLUSIONS: NBV-MB infection triggered autophagy. Also, the NBV nonstructural protein µNS may contribute to augmentation of autophagy upon viral infection.

Safety and effectiveness of day-surgery laparoscopic cholecystectomy is still uncertain: meta-analysis of eight randomized controlled trials based on GRADE approach.

BACKGROUND: Currently, there is no consensus on whether laparoscopic cholecystectomy (LC) performed as day-surgery is safe and effective and can be considered as the standard for the management of symptomatic gallbladder disease. We conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the safety and effectiveness of this intervention based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. METHODS: We conducted a systematic search of several databases from their inception to November 10, 2016 for entries on the mortality, morbidity after discharge, readmission, postoperative morbidity, and patient satisfaction at 1 week of day-surgery LC. Pooled risk ratio (RR) with 95% confidence intervals (CI) was calculated using the fixed-effects model. Rare outcomes were presented as the Peto odds ratio (Peto OR). Meta-analysis was performed by using the RevMan 5.1 software, and the level of evidence was assessed by using the GRADE guideline and GRADEpro GDT software. RESULTS: Eight RCTs totaling 624 participants were included. The result showed no intergroup difference in short-term mortality. Compared to overnight-stay surgery, day-surgery did not show any clear evidence of reduced morbidity after discharge (Peto OR 0.89; 95% CI 0.39-2.02), lower readmission rate (Peto OR 0.68; 95% CI 0.23-2.05), or higher postoperative morbidity rates (RR 1.28; 95% CI 0.81-2.02). However, the results suggested that day-surgery may improve patient satisfaction at 1 week (RR 1.17; 95% CI 1.03-1.33). Evaluation by the GRADE approach revealed that the quality of evidence for each outcome was of low to very low quality due to the risk of bias, imprecision, and inconsistency. CONCLUSION: Our meta-analysis shows that the safety and effectiveness of day-surgery LC is still uncertain. Additional well-designed and adequately powered RCTs are required before the procedure can be recommended as the standard for clinical practice.

Topical phenytoin for treating pressure ulcers.

BACKGROUND: Pressure ulcers are common in clinical practice and pose a significant health problem worldwide. Apart from causing suffering to patients, they also result in longer hospital stays and increase the cost of health care. A variety of methods are used for treating pressure ulcers, including pressure relief, patient repositioning, biophysical strategies, nutritional supplementation, debridement, topical negative pressure, and local treatments including dressings, ointments and creams such as bacitracin, silver sulphadiazine, neomycin, and phenytoin. Phenytoin is a drug more commonly used in the treatment of epilepsy, but may play an important role in accelerating ulcer healing. OBJECTIVES: To assess the effects of topical phenytoin on the rate of healing of pressure ulcers of any grade, in any care setting. SEARCH METHODS: In September 2016, we searched the following electronic databases to identify relevant randomized clinical trials: the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library); Ovid MEDLINE; Ovid Embase; and EBSCO CINAHL Plus. We handsearched conference proceedings from the European Pressure Ulcer Advisory Panel, European Wound Management Association and the Tissue Viability Society for all available years. We searched the references of the retrieved trials to identify further relevant trials. We also searched clinical trials registries to identify ongoing and unpublished studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) addressing the effects (both benefits and harms) of topical phenytoin on the healing of pressure ulcers of any grade compared with placebo or alternative treatments or no therapy, irrespective of blinding, language, and publication status. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, extracted information on participants, interventions, methods and results and assessed risk of bias using Cochrane methodological procedures. For dichotomous variables, we calculated the risk ratio (RR) with 95% confidence interval (CI). For continuous variables, we calculated the mean difference with 95% CI. We rated the quality of the evidence by using Grading of Recommendations, Assessment, Development and Evaluation approach (GRADE). MAIN RESULTS: Three small RCTs met our inclusion criteria and included a total of 148 participants. These compared three treatments with topical phenytoin: hydrocolloid dressings, triple antibiotic ointment and simple dressings. In the three RCTs, 79% of participants had grade II ulcers, and 21% of participants had grade I ulcers; no participants had grade III or IV ulcers. Two RCTs had a high risk of bias overall and the other RCT was at unclear risk of bias due to poor reporting. Two RCTs had three intervention arms and the other had two intervention arms.Two studies compared topical phenytoin with hydrocolloid dressing (84 participants analysed). The available data suggest that hydrocolloid dressings may improve ulcer healing compared to topical phenytoin (39.3% ulcers healed for phenytoin versus 71.4% ulcers healed for hydrocolloid dressings (RR 0.55, 95% CI 0.33 to 0.92; 56 participants, 1 study; low quality evidence). We downgraded the evidence twice: once due to serious limitations (high risk of bias) and once due to the small sample size and small number of events. Two studies compared topical phenytoin with simple dressings (81 participants analysed). From the available data, we are uncertain whether topical phenytoin improves ulcer healing compared to simple dressings (39.3% ulcers healed for phenytoin versus 29.6% ulcers healed for the simple dressing (RR 1.33, 95% CI 0.63 to 2.78; 55 participants, 1 study; very low quality evidence). This evidence was downgraded once due to serious limitations (high risk of bias) and twice due to the low number of outcome events and resulting wide CI which included the possibility of both increased healing and reduced healing. We therefore considered it to be insufficient to determine the effect of topical phenytoin on ulcer healing. One study compared topical phenytoin with triple antibiotic ointment, however, none of the outcomes of interest to this review were reported. No adverse drug reactions or interactions were detected in any of the three RCTs. Minimal pain was reported in all groups in one trial that compared topical phenytoin with hydrocolloid dressings and triple antibiotic ointment. AUTHORS' CONCLUSIONS: This review has considered the available evidence and the result shows that it is uncertain whether topical phenytoin improves ulcer healing for patients with grade I and II pressure ulcers. No adverse events were reported from three small trials and minimal pain was reported in one trial. Therefore, further rigorous, adequately powered RCTs examining the effects of topical phenytoin for treating pressure ulcers, and to report on adverse events, quality of life and costs are necessary.

Intestinal removal of free fatty acids from hosts by Lactobacilli for the treatment of obesity.

Recent findings on the association of gut microbiota with various diseases, including obesity, prompted us to investigate the possibility of using a certain type of gut bacteria as a safe therapeutic for obesity. Lactobacillus mutants with enhanced capacity in absorption of free fatty acids (FFAs) were isolated to show reduced absorption of FFAs by the administered host, attributing to inhibition of body weight gain and body fat accumulation as well as amelioration of blood profiles. Consequently, high throughput screening of natural FFAs-absorbing intestinal microbes led to the isolation of Lactobacillus reuteri JBD30 l. The administration of Lactobacillus JBD30l lowered the concentration of FFAs in the gut fluid content of small intestine, thus reducing intestinal absorption of FFAs whereas promoting fecal excretion of FFAs. Animal data also confirmed that the efficacy of Lactobacillus JBD30l on body weight similar to that of orlistat, an FDA-approved pharmaceutical for long-term use to treat obesity. In a subsequent random, double-blind, placebo-controlled clinical trial (KCT0000452 at Clinical Research Information Service of Korea), there was a statistically significant difference in the percentage change in body weight between the Lactobacillus JBD301 and the placebo group (P = 0.026) as well as in the BMI (P = 0.036) from the 0-week assessment to the 12-week assessment. Our results show that FFA-absorbing Lactobacillus JBD301 effectively reduces dietary fat absorption, providing an ideal treatment for obesity with inherent safety.

A novel cold-active lipase from Candida albicans: cloning, expression and characterization of the recombinant enzyme.

A novel lipase gene lip5 from the yeast Candida albicans was cloned and sequenced. Alignment of amino acid sequences revealed that 86-34% identity exists with lipases from other Candida species. The lipase and its mutants were expressed in the yeast Pichia pastoris, where alternative codon usage caused the mistranslation of 154-Ser and 293-Ser as leucine. 154-Ser to leucine resulted in loss of expression of Lip5, and 293-Ser to leucine caused a marked reduction in the lipase activity. Lip5-DM, which has double mutations that revert 154 and 293 to serine residues, showed good lipase activity, and was overexpressed and purified by (NH(4))(2)SO(4) precipitation and ion-exchange chromatography. The pure Lip5-DM was stable at low temperatures ranging from 15-35 °C and pH 5-9, with the optimal conditions being 15-25 °C and pH 5-6. The activation energy of recombinant lipase was 8.5 Kcal/mol between 5 and 25 °C, suggesting that Lip5-DM was a cold-active lipase. Its activity was found to increase in the presence of Zn(2+), but it was strongly inhibited by Fe(2+), Fe(3+), Hg(2+) and some surfactants. In addition, the Lip5-DM could not tolerate water-miscible organic solvents. Lip5-DM exhibited a preference for the short-and medium-chain length p-nitrophenyl (C4 and C8 acyl group) esters rather than the long chain length p-nitrophenyl esters (C12, C16 and C18 acyl group) with highest activity observed with the C8 derivatives. The recombinant enzyme displayed activity toward triacylglycerols, such as olive oil and safflower oil.

(E)-1-Methyl-5-(3-methyl-4-chloro-phen-oxy)-3-trifluoro-meth-yl-1H-pyrazole-4-carbaldehyde O-acetyl-oxime.

In the title mol-ecule, C(15)H(13)ClF(3)N(3)O(3), the pyrazole and benzene rings form a dihedral angle of 77.6 (3)°. In the crystal, mol-ecules related by translation along the a axis are linked into chains via C-H⋯O hydrogen bonds. The crystal packing is stabilized further by weak π-π [centroid-centroid distance = 3.734 (6) Å] and dipole-dipole inter-actions [C⋯O = 3.174 (2) Å].

Omi is a mammalian heat-shock protein that selectively binds and detoxifies oligomeric amyloid-beta.

The cellular generation of toxic metabolites and subsequent detoxification failure can cause the uncontrolled accumulation of these metabolites in cells, leading to cellular dysfunction. Amyloid-beta protein (Abeta), a normal metabolite of neurons, tends to form toxic oligomeric structures that cause neurodegeneration. It is unclear how healthy neurons control the levels of intracellular oligomeric Abeta in order to avoid neurodegeneration. Using immunochemical and biochemical studies, we show that the Abeta-binding serine protease Omi is a stress-relieving heat-shock protein that protects neurons against neurotoxic oligomeric Abeta. Through its PDZ domain, Omi binds preferentially to neurotoxic oligomeric forms of Abeta rather than non-toxic monomeric forms to detoxify oligomeric Abeta by disaggregation. This specific interaction leads not only to mutual detoxification of the pro-apoptotic activity of Omi and Abeta-induced neurotoxicity, but also to a reduction of neurotoxic-Abeta accumulation. The neuroprotective role of Omi is further supported by its upregulation during normal neurogenesis and neuronal maturation in mice, which could be in response to the increase in the generation of oligomeric Abeta during these processes. These findings provide novel and important insights into the detoxification pathway of intraneuronal oligomeric Abeta in mammals and the protective roles of Omi in neurodegeneration, suggesting a novel therapeutic target in neurodegenerative diseases.

Transgenic mice with neuron-specific overexpression of HtrA2/Omi suggest a neuroprotective role for HtrA2/Omi.

Mammalian serine protease HtrA2/Omi has been known as an apoptosis inducer involved inactivation of caspase-dependent as well as caspase-independent cell death. Recent studies with the HtrA2/Omi mutant and knockout mouse models, however, suggested that HtrA2/Omi might play a protective role in neurons. It is important to establish a transgenic mouse model with neuron-specific overexpression of HtrA2/Omi to clarify the physiological function of mammalian HtrA2/Omi in neurons. In the present study, a transgene containing HtrA2/Omi cDNA downstream of a rat neuron-specific enolase promoter was constructed and microinjected into the pronuclei of fertilized zygotes to establish transgenic mice. Transgenic mice successfully overexpressed HtrA2/Omi in brain tissue. As expected, HtrA2/Omi-overexpressing transgenic mice showed normal development without any sign of apoptotic cell death. Our results suggest that the primary function of neuronal HtrA2/Omi might be to protect neurons against stress in contrast to its role in the somatic system.