Development of a servo-controller of heart rate using a treadmill

Although treadmill exercise involves a more familiar range of motions and is thus more physiological in terms of daily activity than cycle ergometer exercise, difficulties in controlling the exercise intensity have limited its utility. As heart rate (HR) has been used as a measure of exercise intensity, controlling HR should allow for the proper control of exercise intensity during treadmill exercise. Thus, a servo-controller framework was applied to regulate HR during treadmill exercise. After estimating an averaged transfer function from speed command to HR, feedback parameters were optimized via a computer simulation in order to achieve a quick and stable HR response. The performance of the servo-controller of HR was then examined in 10 healthy subjects. Standard deviations of the steady-state difference between the target and measured HRs were 2.7+/-0.9 and 5.0+/-1.4 beats/min in the stepwise and ramp target HR protocols, respectively. The rise time to reach 90% of the target HR was 93+/-20 s in the stepwise protocol. It was concluded that a treadmill implemented with a negative feedback mechanism made it possible to precisely regulate HR and thus exercise intensity.     

Alternating contractility in pulsus alternans studied in the isolated canine heart

We examined pulsus alternans in seven isolated, perfused canine left ventricles ejecting into a simulated arterial impedance. Left ventricular pressure-volume loops were measured during pulsus alternans while filing-source pressure was lowered. In all cases two distinct linear end-systolic pressure-volume relationships (ESPVRs) were noted for the strong and weak beats. The slopes of the ESPVRs of the strong beats were significantly greater than those of the weak beats (mean difference 0.9 +/- 0.6 mm Hg/ml, p less than .01), while the intercepts were not significantly different (mean difference 0.06 +/- 0.5 ml). Diastolic pressure-volume relationships for the strong and weak beats were not significantly different, excluding incomplete relaxation as a cause of pulsus alternans. Although the weak beats had both a smaller preceding end-diastolic volume and a larger end-systolic volume, the presence of two distinct ESPVRS for the strong and weak beats shows there is alternating ventricular chamber contractility in pulsus alternans that is not solely due to the Starling mechanism. The magnitude of alternation in pump function parameters such as pressure and stroke volume during pulsus alternans reflects the complex interactions of alternating contractile state with alternations in preload and afterload.     

Interleukin-17A promotes rheumatoid arthritis synoviocytes migration and invasion under hypoxia by increasing MMP2 and MMP9 expression through NF-κB/HIF-1α pathway

Both hypoxia and interleukin-17A (IL-17A) promote the migration and invasion of fibroblast-like synoviocytes (FLSs), which are critical for the pathogenesis of rheumatoid arthritis (RA). However, the biochemical pathways regulating IL-17A combined with hypoxia are not well defined. In this study, we found that co-stimulating RA-FLSs with IL-17A and hypoxia did not appear to promote the epithelial–mesenchymal transition (EMT), but did increase cell motility. We further showed that a proinvasive effect of IL-17A on FLSs under hypoxia might be through upregulation of matrix metalloproteinase 2 (MMP2) and MMP9. Moreover, IL-17A-induced expression of MMP2 and MMP9 under hypoxia was accompanied by increased activation of nuclear factor-κB (NF-κB)/hypoxia-inducible factor-1α (HIF-1α). Knockdown or inhibition of HIF-1α and NF-κB by small interfering RNA or specific small molecule inhibitors blocked IL-17A-mediated and hypoxia-mediated MMP2 and MMP9 expression, cell migration, and invasion. In addition, the inhibition of NF-κB led to a marked decrease in the expression of HIF-1α, which indicated that IL-17A activated HIF-1α via the NF-κB pathway in hypoxia. Taken together, our observations suggest a synergetic effect of IL-17A and hypoxia that might contribute to the migration and invasion of RA-FLSs by upregulating the expression of MMP2 and MMP9 by activation of the NF-κB/HIF-1α pathway.     

FASTER: an unsupervised fully automated sleep staging method for mice

Identifying the stages of sleep, or sleep staging, is an unavoidable step in sleep research and typically requires visual inspection of electroencephalography (EEG) and electromyography (EMG) data. Currently, scoring is slow, biased and prone to error by humans and thus is the most important bottleneck for large‐scale sleep research in animals. We have developed an unsupervised, fully automated sleep staging method for mice that allows less subjective and high‐throughput evaluation of sleep. Fully Automated Sleep sTaging method via EEG/EMG Recordings (FASTER) is based on nonparametric density estimation clustering of comprehensive EEG/EMG power spectra. FASTER can accurately identify sleep patterns in mice that have been perturbed by drugs or by genetic modification of a clock gene. The overall accuracy is over 90% in every group. 24‐h data are staged by a laptop computer in 10 min, which is faster than an experienced human rater. Dramatically improving the sleep staging process in both quality and throughput FASTER will open the door to quantitative and comprehensive animal sleep research.     

A randomized controlled trial of radiofrequency ablation with ethanol injection for small hepatocellular carcinoma

BACKGROUND & AIMS: Percutaneous radiofrequency ablation is a recently introduced treatment for hepatocellular carcinoma, whereas ethanol injection is now a standard therapy. We compared their long-term outcomes. METHODS: Two hundred thirty-two patients with hepatocellular carcinoma who had 3 or fewer lesions, each 3 cm or less in diameter, and liver function of Child-Pugh class A or B were entered onto a randomized controlled trial. The primary end point was survival, and the secondary end points were overall recurrence and local tumor progression. RESULTS: One hundred eighteen patients were assigned to radiofrequency ablation and 114 to ethanol injection. The number of treatment sessions was smaller (2.1 times vs 6.4 times, respectively, P < .0001) and the length of hospitalization was shorter (10.8 days vs 26.1 days, respectively, P < .0001) in radiofrequency ablation than in ethanol injection. Four-year survival rate was 74% (95% CI: 65%-84%) in radiofrequency ablation and 57% (95% CI: 45%-71%) in ethanol injection. Radiofrequency ablation had a 46% smaller risk of death (adjusted relative risk, 0.54 [95% CI: 0.33-0.89], P = .02), a 43% smaller risk of overall recurrence (adjusted relative risk 0.57 [95% CI: 0.41-0.80], P = .0009), and an 88% smaller risk of local tumor progression (relative risk, 0.12 [95% CI: 0.03-0.55], P = .006) than ethanol injection. The incidence of adverse events was not different between the 2 therapies. CONCLUSIONS: Judging from higher survival but similar adverse events, radiofrequency ablation is superior to ethanol injection for small hepatocellular carcinoma.     

Spindle cell carcinoma arising at the buccal mucosa: a case report and review of the literature

Aims:

Spindle cell carcinoma (SPCC) is a subtype of squamous cell carcinoma, and it mainly occurs in the upper aerodigestive duct. On the other hand, it rarely arises in the head and neck region. The prognosis of this tumor is usually poor because of its highly malignant behavior, such as its high incidence of recurrence or metastasis to cervical lymph nodes. However, the number of accumulated cases is still too low to provide the full details of SPCC.

Methodology:

The case of SPCC was counted by using database, PubMed. The authors also present a case of SPCC arising at the left buccal mucosa in a 72-year-old Japanese female in the current study.

Results:

Only six cases of SPCC arising at the buccal mucosa have been reported previously. The authors’ patient died from a recurrent tumor 15 months after the first operation.

Conclusion:

The authors have added this case to the previous knowledge of SPCC arising at the buccal mucosa, and discuss the clinical behavior of SPCC to help suggest a standard treatment strategy for the disease.     

Tips for endoscopic ultrasound‐guided fine needle aspiration of various pancreatic lesions

Endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) is a well‐established procedure for diagnosis of pancreatic solid masses. This technique is highly accurate and safe and can be performed uneventfully in most cases. However, factors such as unstable scope position, inappropriate location of the lesion, lesion mobility, and lesion characteristics may complicate the procedure. To overcome such difficulties, it is necessary to select the most suitable needle and consider several technical points according to each situation. We introduce our standard technique for EUS‐FNA and provide several tips for ensuring a successful procedure.