Author Correction: Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity.

Direct recognition of invading pathogens by innate immune cells is a critical driver of the inflammatory response. However, cells of the innate immune system can also sense their local microenvironment and respond to physiological fluctuations in temperature, pH, oxygen and nutrient availability, which are altered during inflammation. Although cells of the immune system experience force and pressure throughout their life cycle, little is known about how these mechanical processes regulate the immune response. Here we show that cyclical hydrostatic pressure, similar to that experienced by immune cells in the lung, initiates an inflammatory response via the mechanically activated ion channel PIEZO1. Mice lacking PIEZO1 in innate immune cells showed ablated pulmonary inflammation in the context of bacterial infection or fibrotic autoinflammation. Our results reveal an environmental sensory axis that stimulates innate immune cells to mount an inflammatory response, and demonstrate a physiological role for PIEZO1 and mechanosensation in immunity.

Effects of embryo temperature estimation methodology on the determination of eggshell conductance values in Ross 708 broiler hatching eggs with consideration given to eggshell pigmentation variation.

In a preliminary experiment, the influence of pigment color variation on the temperature readings of the shells (EST) of live embryonated Ross 708 broiler hatching eggs was tested. Prior to set, eggshell color in L*, a*, and b* coordinates were measured at the equator of each egg. Eggshell pigmentation was found not to influence EST from zero through 18 d of incubation (DOI). In a subsequent experiment, EST, as well as air cell (ACT) and cloaca (CLT) temperature measurements were used for the calculation of absolute (GH2O) and specific (gH20) eggshell conductance values for these same types of eggs. An infrared thermometer was used to determine EST from zero to 19 DOI, ACT was measured using a transponder from 12 to 19 DOI, and CLT was determined using a transponder at 4:00 PM at 19 DOI. In the 12 to 19 DOI interval, the values for GH2O as well as for gH20 that were calculated using either EST or ACT were significantly correlated (r ≥ 0.99; P < 0.0001). A similar correlation level for both GH2O and gH20 was likewise observed in the 10:00 AM to 10:00 PM time period at 19 DOI when either EST, ACT, or CLT was used. However, in the 12 to 19 DOI interval, calculated GH2O and gH20 values based on ACT were significantly different from those based on EST. In addition, a significant difference in calculated GH2O and gH20 values resulted when ACT was used rather than when EST or CLT was used in the 10:00 AM to 10:00 PM time period at 19 DOI. In both time periods, GH2O and gH20 values calculated using ACT were significantly lower than those derived using the other 2 types of measurements. These findings suggest that although EST was not affected by shell coloration, because ACT more closely reflects embryo body temperature, it should be used to more accurately calculate the GH2O and gH20 of Ross 708 broiler hatching eggs.

Benchtop testing and comparisons among three types of through-the-scope endoscopic clipping devices.

BACKGROUND: Through-the-scope (TTS) endoscopic clipping devices are widely used. No benchtop testing or direct comparisons of these endoclips have been performed to show their rotational ability and inherent mechanical strengths during closure and after deployment. This study aimed to provide benchtop data that can be used to guide clinical applications and to promote future device research and development. METHODS: Benchtop testing and comparisons were performed for three groups of TTS clips: QuickClip2 long, resolution, and instinct clips. The main outcome measurements were device-in-endoscope retroflection angles (DIERA), opening strength, "snapping" force of acute clip closure, and neoprene pulling strength. RESULTS: The achievable gastroscope DIERA was 10° for QuickClip2, 3° for the resolution clip, and 10° for the instinct clip. The QuickClip and the Instinct clip rotated almost equally well under all endoscope configurations, including endoscopic retrograde cholangiopancreatography (ERCP). With or without a sheath, the resolution clip lacked the ability to rotate. During clip opening force testing (the amount of force required to force open the jaws of a deployed clip by 3.2 mm; 3.2 mm was chosen due to the standard dimension of the gauge used for the measurement), the Instinct clips were the strongest. For the Instinct clips, an opening force of 404 ± 124 g was needed to open the closed clip, and an additional 386 ± 133 g was required to open the clip jaws to 3.2 mm. In terms of snapping force during acute closure and neoprene pulling strength, the instinct and resolution clips performed almost equally. The limitations of the study were the benchtop testing and the finite sample size for closing and pulling strength comparisons. CONCLUSIONS: The QuickClip2 and the Instinct clip rotate equally well under different endoscope configurations. The resolution clips lack rotational ability. The instinct clips are stronger mechanically than the other two TTS clips. Stronger clips are perhaps associated with higher therapeutic efficacy and retention rates.

Development of innovative techniques for the endoscopic implantation and securing of a novel, wireless, miniature gastrostimulator (with videos).

BACKGROUND: Gastric stimulation via high-frequency, low-energy pulses can provide an effective treatment for gastric dysmotility; however, the current commercially available device requires surgical implantation for long-term stimulation and is powered by a nonrechargeable battery. OBJECTIVE: To test and describe endoscopic implantation techniques and testing of stimulation of a novel, wireless, batteryless, gastric electrical stimulation (GES) device. DESIGN: Endoscopic gastric implantation techniques were implemented, and in vivo gastric signals were recorded and measured in a non-survival swine model (n = 2; 50-kg animals). INTERVENTION: Five novel endoscopic gastric implantation techniques and stimulation of a novel, wireless, batteryless, GES device were tested on a non-survival swine model. MAIN OUTCOME MEASUREMENTS: Feasibility of 5 new endoscopic gastric implantation techniques of the novel, miniature, batteryless, wireless GES device while recording and measurement of in vivo gastric signals. RESULTS: All 5 of the novel endoscopic techniques permitted insertion and securing of the miniaturized gastrostimulator. By the help of these methods and miniaturization of the gastrostimulator, successful GES could be provided without any surgery. The metallic clip attachment was restricted to the mucosal surface, whereas the prototype tacks, prototype spring coils, percutaneous endoscopic gastrostomy wires/T-tag fasteners, and submucosal pocket endoscopic implantation methods attach the stimulator near transmurally or transmurally to the stomach. They allow more secure device attachment with optimal stimulation depth. LIMITATIONS: Non-survival pig studies. CONCLUSION: These 5 techniques have the potential to augment the utility of GES as a treatment alternative, to provide an important prototype for other dysmotility treatment paradigms, and to yield insights for new technological interfaces between non-invasiveness and surgery.

An endoscopic wireless gastrostimulator (with video).

BACKGROUND: Gastric electric stimulation (GES) at a high-frequency, low-energy setting is an option for treating refractory gastroparesis. The currently available commercial stimulator, the Enterra neurostimulator (Medtronic Inc, Minneapolis, MN), however, requires surgical implantation and is powered by a nonrechargeable battery. OBJECTIVE: To develop and test a miniature wireless GES device for endoscopic implantation in an experimental model. DESIGN: In-vivo gastric signals were recorded and measured in a nonsurvival swine model (n = 2; 110-lb animals). INTERVENTION: An endoscopically placed, wireless GES device was inserted into the stomach through an overtube; the two GES electrodes were endoscopically attached to the gastric mucosa and secured with endoclips to permit stimulation. MAIN OUTCOME MEASUREMENTS: Stable electrogastrogram measures were observed during GES stimulation. RESULTS: Electrogastrogram recordings demonstrated that gastric slow waves became more regular and of constant amplitudes when stomach tissues were stimulated, in comparison with no stimulation. The frequency-to-amplitude ratio also changed significantly with stimulation. LIMITATION: Nonsurvival pig studies. CONCLUSION: Gastric electric stimulation is feasible by our endoscopically implanted, wireless GES device.

Design of a cyclic pressure bioreactor for the ex vivo study of aortic heart valves.

The aortic valve, located between the left ventricle and the aorta, allows for unidirectional blood flow, preventing backflow into the ventricle. Aortic valve leaflets are composed of interstitial cells suspended within an extracellular matrix (ECM) and are lined with an endothelial cell monolayer. The valve withstands a harsh, dynamic environment and is constantly exposed to shear, flexion, tension, and compression. Research has shown calcific lesions in diseased valves occur in areas of high mechanical stress as a result of endothelial disruption or interstitial matrix damage(1-3). Hence, it is not surprising that epidemiological studies have shown high blood pressure to be a leading risk factor in the onset of aortic valve disease(4). The only treatment option currently available for valve disease is surgical replacement of the diseased valve with a bioprosthetic or mechanical valve(5). Improved understanding of valve biology in response to physical stresses would help elucidate the mechanisms of valve pathogenesis. In turn, this could help in the development of non-invasive therapies such as pharmaceutical intervention or prevention. Several bioreactors have been previously developed to study the mechanobiology of native or engineered heart valves(6-9). Pulsatile bioreactors have also been developed to study a range of tissues including cartilage(10), bone(11) and bladder(12). The aim of this work was to develop a cyclic pressure system that could be used to elucidate the biological response of aortic valve leaflets to increased pressure loads. The system consisted of an acrylic chamber in which to place samples and produce cyclic pressure, viton diaphragm solenoid valves to control the timing of the pressure cycle, and a computer to control electrical devices. The pressure was monitored using a pressure transducer, and the signal was conditioned using a load cell conditioner. A LabVIEW program regulated the pressure using an analog device to pump compressed air into the system at the appropriate rate. The system mimicked the dynamic transvalvular pressure levels associated with the aortic valve; a saw tooth wave produced a gradual increase in pressure, typical of the transvalvular pressure gradient that is present across the valve during diastole, followed by a sharp pressure drop depicting valve opening in systole. The LabVIEW program allowed users to control the magnitude and frequency of cyclic pressure. The system was able to subject tissue samples to physiological and pathological pressure conditions. This device can be used to increase our understanding of how heart valves respond to changes in the local mechanical environment.