Application of Mathematical Models in Combination with Monte Carlo Simulation for Prediction of Isoflurane Concentration in an Operation Room Theater

Applicability of two mathematical models in inhalation exposure prediction (well mixed room and near field-far field model) were validated against standard sampling method in one operation room for isoflurane. Ninety six air samples were collected from near and far field of the room and quantified by gas chromatography-flame ionization detector. Isoflurane concentration was also predicted by the models. Monte Carlo simulation was used to incorporate the role of parameters variability. The models relatively gave more conservative results than the measurements. There was no significant difference between the models and direct measurements results. There was no difference between the concentration prediction of well mixed room model and near field far field model. It suggests that the dispersion regime in room was close to well mixed situation. Direct sampling showed that the exposure in the same room for same type of operation could be up to 17 times variable which can be incorporated by Monte Carlo simulation. Mathematical models are valuable option for prediction of exposure in operation rooms. Our results also suggest that incorporating the role of parameters variability by conducting Monte Carlo simulation can enhance the strength of prediction in occupational hygiene decision making.     

Detection of prostate cancer using temporal sequences of ultrasound data: a large clinical feasibility study

Purpose

This paper presents the results of a large study involving fusion prostate biopsies to demonstrate that temporal ultrasound can be used to accurately classify tissue labels identified in multi-parametric magnetic resonance imaging (mp-MRI) as suspicious for cancer.

Methods

We use deep learning to analyze temporal ultrasound data obtained from 255 cancer foci identified in mp-MRI. Each target is sampled in axial and sagittal planes. A deep belief network is trained to automatically learn the high-level latent features of temporal ultrasound data. A support vector machine classifier is then applied to differentiate cancerous versus benign tissue, verified by histopathology. Data from 32 targets are used for the training, while the remaining 223 targets are used for testing.

Results

Our results indicate that the distance between the biopsy target and the prostate boundary, and the agreement between axial and sagittal histopathology of each target impact the classification accuracy. In 84 test cores that are 5 mm or farther to the prostate boundary, and have consistent pathology outcomes in axial and sagittal biopsy planes, we achieve an area under the curve of 0.80. In contrast, all of these targets were labeled as moderately suspicious in mp-MR.

Conclusion

Using temporal ultrasound data in a fusion prostate biopsy study, we achieved a high classification accuracy specifically for moderately scored mp-MRI targets. These targets are clinically common and contribute to the high false-positive rates associated with mp-MRI for prostate cancer detection. Temporal ultrasound data combined with mp-MRI have the potential to reduce the number of unnecessary biopsies in fusion biopsy settings.

     

The analgesic effect of inhalational Entonox for extracorporeal shock wave lithotripsy

Extracorporeal shock wave lithotripsy (ESWL) is a non-invasive procedure that allows urinary stones to be fragmented using acoustic shock waves. The impact of the shock waves causes transient stinging pain at the entry site as well as deep visceral discomfort, requiring analgesia during the procedure. The objective of this study was to compare the clinical efficacy of Entonox and pethidine for pain relief during outpatient ESWL. We randomized 150 outpatients undergoing elective ESWL into three groups of 50 patients, each group receiving inhalational Entonox, intravenous pethidine, or inhalational compressed air during ESWL. Quantitative evaluation of pain was performed according to a visual analogue scale (VAS), before and after the intervention. Analysis of variance (ANOVA) and paired t tests were used to compare VAS scores in the three groups, before and after the intervention. Entonox and pethidine decreased the pain score significantly, while compressed air did not. There was no significant difference between pain relief by Entonox and pethidine. This study demonstrates for the first time that inhalational Entonox is an effective analgesic regimen for ESWL. Entonox can be regarded as an appropriate alternative to analgesics like opioids in relieving pain during ESWL.     

Expression regulation of chitin-binding protein and metal-binding peptide in new Bacillus velezensis: MALDI-TOF MS/MS analysis

Metallothionein and metal-binding peptides are small cysteine-rich proteins produced by different organisms in stress conditions. In this study, the metal-binding peptide was detected in extracellular proteins of a new Bacillus velezensis strain, isolated from metal contaminated soil, and grown on the lead-enriched medium, for the first time. The presence of sulfide peptide was assayed by two simple tests (lead sulfide and Ellman's reagent test) for preliminary, and subsequently confirmed using polyacrylamide gel electrophoresis at media with different lead concentrations that the low-molecular-weight protein fragments (≈10 kDa) were observed while none were detected in the medium containing sodium chloride or calcium salt. The amino acids of the observed fragments were analyzed by matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF MS/MS). Also, the metal adsorption was confirmed using sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) by staining with chromium solution. The results showed that the putative sulfide peptide is metallothionein, which is induced in stress conditions. It was interesting that in all SDS profiles, one protein fragment (≈18 kDa) was inhibited in lead-enriched media. The data from MALDI-TOF MS/MS analysis showed that this fraction was a chitin-binding protein whose production was regulated by metal contamination. It is anticipated that these two proteins regulate the toxicity of lead.     

Detection and grading of prostate cancer using temporal enhanced ultrasound: combining deep neural networks and tissue mimicking simulations

Purpose 

Temporal Enhanced Ultrasound (TeUS) has been proposed as a new paradigm for tissue characterization based on a sequence of ultrasound radio frequency (RF) data. We previously used TeUS to successfully address the problem of prostate cancer detection in the fusion biopsies.

Methods 

In this paper, we use TeUS to address the problem of grading prostate cancer in a clinical study of 197 biopsy cores from 132 patients. Our method involves capturing high-level latent features of TeUS with a deep learning approach followed by distribution learning to cluster aggressive cancer in a biopsy core. In this hypothesis-generating study, we utilize deep learning based feature visualization as a means to obtain insight into the physical phenomenon governing the interaction of temporal ultrasound with tissue.

Results 

Based on the evidence derived from our feature visualization, and the structure of tissue from digital pathology, we build a simulation framework for studying the physical phenomenon underlying TeUS-based tissue characterization.

Conclusion 

Results from simulation and feature visualization corroborated with the hypothesis that micro-vibrations of tissue microstructure, captured by low-frequency spectral features of TeUS, can be used for detection of prostate cancer.

     

Neuregulin‐1 promotes remyelination and fosters a pro‐regenerative inflammatory response in focal demyelinating lesions of the spinal cord

Oligodendroglial cell death and demyelination are hallmarks of neurotrauma and multiple sclerosis that cause axonal damage and functional impairments. Remyelination remains a challenge as the ability of endogenous precursor cells for oligodendrocyte replacement is hindered in the unfavorable milieu of demyelinating conditions. Here, in a rat model of lysolecithin lysophosphatidyl‐choline (LPC)‐induced focal demyelination, we report that Neuregulin‐1 (Nrg‐1), an important factor for oligodendrocytes and myelination, is dysregulated in demyelinating lesions and its bio‐availability can promote oligodendrogenesis and remyelination. We delivered recombinant human Nrg‐1β1 (rhNrg‐1β1) intraspinally in the vicinity of LPC demyelinating lesion in a sustained manner using poly lactic‐co‐glycolic acid microcarriers. Availability of Nrg‐1 promoted generation and maturation of new oligodendrocytes, and accelerated endogenous remyelination by both oligodendrocyte and Schwann cell populations in demyelinating foci. Importantly, Nrg‐1 enhanced myelin thickness in newly remyelinated spinal cord axons. Our complementary in vitro studies also provided direct evidence that Nrg‐1 significantly promotes maturation of new oligodendrocytes and facilitates their transition to a myelinating phenotype. Nrg‐1 therapy remarkably attenuated the upregulated expression chondroitin sulfate proteoglycans (CSPGs) specific glycosaminoglycans in the extracellular matrix of demyelinating foci and promoted interleukin‐10 (IL‐10) production by immune cells. CSPGs and IL‐10 are known to negatively and positively regulate remyelination, respectively. We found that Nrg‐1 effects are mediated through ErbB2 and ErbB4 receptor activation. Our work provides novel evidence that dysregulated levels of Nrg‐1 in demyelinating lesions of the spinal cord pose a challenge to endogenous remyelination, and appear to be an underlying cause of myelin thinning in newly remyelinated axons.