A methoxylated fatty acid isolated from the brown seaweed Ishige okamurae inhibits bacterial phospholipase A2

A methoxylated fatty acid that inhibits phospholipase A(2) (PLA(2); EC 3.1.1.4) was purified from the brown seaweed Ishige okamurae. Approximately 8.1 mg of the inhibitory compound, 7-methoxy-9-methylhexadeca-4,8-dienoic acid, was isolated from 1 kg of I. okamurae powder. Recombinant PLA(2) derived from the pathogenic bacterium Vibrio mimicus was used as the target enzyme. The methoxylated fatty acid compound competitively inhibited PLA(2) with a Ki value of 3.9 microg/mL. The concentrations required for 50% inhibition of PLA(2), oedema and erythema were 1.0 microg/mL, 3.6 mg/mL and 4.6 mg/mL, respectively. The compound strongly inhibited PLA(2) activity in vitro and had potent antiinflammatory activity in vivo.     

How to Optimally Apply Impedance in the Evaluation of Esophageal Dysmotility

The utilization of impedance technology has enhanced our understanding and assessment of esophageal dysmotility. Esophageal high-resolution manometry (HRM) catheters incorporated with multiple impedance electrodes help assess esophageal bolus transit, and the combination is termed high-resolution impedance manometry (HRIM). Novel metrics have been developed with HRIM—including esophageal impedance integral ratio, bolus flow time, nadir impedance pressure, and impedance bolus height—that augments the assessment of esophageal bolus transit. Automated impedance-manometry (AIM) analysis has enhanced understanding of the relationship between bolus transit and pressure phenomena. Impedance-based metrics have improved understanding of the dynamics of esophageal bolus transit into four distinct phases, may correlate with symptomatic burden, and can assess the adequacy of therapy for achalasia. An extension of the use of impedance involves impedance planimetry and the functional lumen imaging probe (FLIP), which assesses esophageal biophysical properties and distensibility, and could detect patterns of esophageal contractility not seen on HRM. Impedance technology, therefore, has a significant impact on esophageal function testing in the present day.     

A new approach to determine solar potential using terrestrial images

Before installing Photovoltaic (PV) panels at a place it is important to estimate the solar potential of the place. Most approaches available in literature do not consider the presence of surrounding obstructions, thus leading to wrong estimates. Light Detection and Ranging (LiDAR) data or 3D (Geographic Information System) GIS based approaches consider obstructions but prove cost-effective only at city-wide scales. This paper presents a cost-effective, accurate, and scalable approach for this purpose. The proposed approach utilizes terrestrial images of surroundings and identifies obstructions present therein. Using the azimuth and elevation angles of the principal axes of the terrestrial images the azimuth and elevation angles of each pixel in these images are determined. Using thresholding and morphological closing the terrestrial images are segmented into sky and non-sky zones. Sun is considered visible at the point of interest if it lies in the sky zone. The position of the Sun is determined using the solar position algorithm and the irradiance reaching the Earth surface is computed using the modified radiative transfer model. Finally, the total irradiance over a chosen time period at a given location is estimated by integrating the irradiances for the duration when the Sun is visible.     

Artificial intelligence automates and augments baseline impedance measurements from pH-impedance studies in gastroesophageal reflux disease

Background

Artificial intelligence (AI) has potential to streamline interpretation of pH-impedance studies. In this exploratory observational cohort study, we determined feasibility of automated AI extraction of baseline impedance (AIBI) and evaluated clinical value of novel AI metrics.

Methods

pH-impedance data from a convenience sample of symptomatic patients studied off (n = 117, 53.1 ± 1.2 years, 66% F) and on (n = 93, 53.8 ± 1.3 years, 74% F) anti-secretory therapy and from asymptomatic volunteers (n = 115, 29.3 ± 0.8 years, 47% F) were uploaded into dedicated prototypical AI software designed to automatically extract AIBI. Acid exposure time (AET) and manually extracted mean nocturnal baseline impedance (MNBI) were compared to corresponding total, upright, and recumbent AIBI and upright:recumbent AIBI ratio. AI metrics were compared to AET and MNBI in predicting  ≥ 50% symptom improvement in GERD patients.

Results

Recumbent, but not upright AIBI, correlated with MNBI. Upright:recumbent AIBI ratio was higher when AET  > 6% (median 1.18, IQR 1.0–1.5), compared to  < 4% (0.95, IQR 0.84–1.1), 4–6% (0.89, IQR 0.72–0.98), and controls (0.93, IQR 0.80–1.09, p ≤ 0.04). While MNBI, total AIBI, and the AIBI ratio off PPI were significantly different between those with and without symptom improvement (p < 0.05 for each comparison), only AIBI ratio segregated management responders from other cohorts. On ROC analysis, off therapy AIBI ratio outperformed AET in predicting GERD symptom improvement when AET was  > 6% (AUC 0.766 vs. 0.606) and 4–6% (AUC 0.563 vs. 0.516) and outperformed MNBI overall (AUC 0.661 vs. 0.313).

Conclusions

BI calculation can be automated using AI. Novel AI metrics show potential in predicting GERD treatment outcome.

     

Dysregulated TGF‐β signaling alters bone microstructure in a mouse model of Loeys‐Dietz syndrome

Loeys‐Dietz syndrome (LDS) is a connective tissue disorder characterized by vascular and skeletal abnormalities resembling Marfan syndrome, including a predisposition for pathologic fracture. LDS is caused by heterozygous mutations in the genes encoding transforming growth factor‐β (TGF‐β) type 1 and type 2 receptors. In this study, we characterized the skeletal phenotype of mice carrying a mutation in the TGF‐β type 2 receptor associated with severe LDS in humans. Cortical bone in LDS mice showed significantly reduced tissue area, bone area, and cortical thickness with increased eccentricity. However, no significant differences in trabecular bone volume were observed. Dynamic histomorphometry performed in calcein‐labeled mice showed decreased mineral apposition rates in cortical and trabecular bone with normal numbers of osteoblasts and osteoclasts. Mechanical testing of femurs by three‐point bending revealed reduced femoral strength and fracture resistance. In vitro, osteoblasts from LDS mice demonstrated increased mineralization with enhanced expression of osteoblast differentiation markers compared with control cells. These changes were associated with impaired TGF‐β1–induced Smad2 and Erk1/2 phosphorylation and upregulated TGF‐β1 ligand mRNA expression, compatible with G357W as a loss‐of‐function mutation in the TGF‐β type 2 receptor. Paradoxically, phosphorylated Smad2/3 in cortical osteocytes measured by immunohistochemistry was increased relative to controls, possibly suggesting the cross‐activation of TGF‐β–related receptors. The skeletal phenotype observed in the LDS mouse closely resembles the principal structural features of bone in humans with LDS and establishes this mouse as a valid in vivo model for further investigation of TGF‐β receptor signaling in bone. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1447–1454, 2015.