Elevated temperature inhibits SARS-CoV-2 replication in respiratory epithelium independently of IFN-mediated innate immune defenses

The pandemic spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of Coronavirus Disease 2019 (COVID-19), represents an ongoing international health crisis. A key symptom of SARS-CoV-2 infection is the onset of fever, with a hyperthermic temperature range of 38 to 41°C. Fever is an evolutionarily conserved host response to microbial infection that can influence the outcome of viral pathogenicity and regulation of host innate and adaptive immune responses. However, it remains to be determined what effect elevated temperature has on SARS-CoV-2 replication. Utilizing a three-dimensional (3D) air–liquid interface (ALI) model that closely mimics the natural tissue physiology of SARS-CoV-2 infection in the respiratory airway, we identify tissue temperature to play an important role in the regulation of SARS-CoV-2 infection. Respiratory tissue incubated at 40°C remained permissive to SARS-CoV-2 entry but refractory to viral transcription, leading to significantly reduced levels of viral RNA replication and apical shedding of infectious virus. We identify tissue temperature to play an important role in the differential regulation of epithelial host responses to SARS-CoV-2 infection that impact upon multiple pathways, including intracellular immune regulation, without disruption to general transcription or epithelium integrity. We present the first evidence that febrile temperatures associated with COVID-19 inhibit SARS-CoV-2 replication in respiratory epithelia. Our data identify an important role for tissue temperature in the epithelial restriction of SARS-CoV-2 independently of canonical interferon (IFN)-mediated antiviral immune defenses.

Assessment and Modeling of Plasmonic Photothermal Therapy Delivered via a Fiberoptic Microneedle Device Ex Vivo

Plasmonic photothermal therapy (PPTT) has potential as a superior treatment method for pancreatic cancer, a disease with high mortality partially attributable to the currently non-selective treatment options. PPTT utilizes gold nanoparticles infused into a targeted tissue volume and exposed to a specific light wavelength to induce selective hyperthermia. The current study focuses on developing this approach within an ex vivo porcine pancreas model via an innovative fiberoptic microneedle device (FMD) for co-delivering light and gold nanoparticles. The effects of laser wavelengths (808 vs. 1064 nm), irradiances (20–50 mW·mm−2), and gold nanorod (GNR) concentrations (0.1–3 nM) on tissue temperature profiles were evaluated to assess and control hyperthermic generation. The GNRs had a peak absorbance at ~800 nm. Results showed that, at 808 nm, photon absorption and subsequent heat generation within tissue without GNRs was 65% less than 1064 nm. The combination of GNRs and 808 nm resulted in a 200% higher temperature rise than the 1064 nm under similar conditions. A computational model was developed to predict the temperature shift and was validated against experimental results with a deviation of <5%. These results show promise for both a predictive model and spatially selective, tunable treatment modality for pancreatic cancer.

Controlled Measurement Setup for Ultra-Wideband Dielectric Modeling of Muscle Tissue in 20–45 ∘C Temperature Range

In order to design electromagnetic applicators for diagnostic and therapeutic applications, an adequate dielectric tissue model is required. In addition, tissue temperature will heavily influence the dielectric properties and the dielectric model should, thus, be extended to incorporate this temperature dependence. Thus, this work has a dual purpose. Given the influence of temperature, dehydration, and probe-to-tissue contact pressure on dielectric measurements, this work will initially present the first setup to actively control and monitor the temperature of the sample, the dehydration rate of the investigated sample, and the applied probe-to-tissue contact pressure. Secondly, this work measured the dielectric properties of porcine muscle in the 0.5–40 GHz frequency range for temperatures from 20 ∘C to 45 ∘C. Following measurements, a single-pole Cole–Cole model is presented, in which the five Cole–Cole parameters (ϵ∞, σs, Δϵ, τ, and α) are given by a first order polynomial as function of tissue temperature. The dielectric model closely agrees with the limited dielectric models known in literature for muscle tissue at 37 ∘C, which makes it suited for the design of in vivo applicators. Furthermore, the dielectric data at 41–45 ∘C is of great importance for the design of hyperthermia applicators.

Systematic Characterization of High-Power Short-Duration Ablation: Insight From an Advanced Virtual Model

Background: High-power short-duration (HPSD) recently emerged as a new approach to radiofrequency (RF) catheter ablation. However, basic and clinical data supporting its effectiveness and safety is still scarce.Objective: We aim to characterize HPSD with an advanced virtual model, able to assess lesion dimensions and complications in multiple conditions and compare it to standard protocols.Methods: We evaluate, on both atrium and ventricle, three HPSD protocols (70 W/8 s, 80 W/6 s, and 90 W/4 s) through a realistic 3D computational model of power-controlled RF ablation, varying catheter tip design (spherical/cylindrical), contact force (CF), blood flow, and saline irrigation. Lesions are defined by the 50°C isotherm contour. Ablations are deemed safe or complicated by pop (tissue temperature &gt;97°C) or charring (blood temperature &gt;80°C). We compared HPSD with standards protocols (30–40 W/30 s). We analyzed the effect of a second HPSD application.Results: We simulated 432 applications. Most (79%) associated a complication, especially in the atrium. The three HPSD protocols performed similarly in the atrium, while 90 W/4 s appeared the safest in the ventricle. Low irrigation rate led frequently to charring (72%). High-power short-duration lesions were 40–60% shallower and smaller in volume compared to standards, although featuring similar width. A second HPSD application increased lesions to a size comparable to standards.Conclusion: High-power short-duration lesions are smaller in volume and more superficial than standards but comparable in width, which can be advantageous in the atrium. A second application can produce lesions similar to standards in a shorter time. Despite its narrow safety margin, HPSD seems a valuable new clinical approach.

EFEKTIVITAS CRYOTHERAPY TERHADAP TINGKAT NYERI PUNGGUNG BAWAH IBU POSTPARTUM PADA MASA PANDEMI COVID-19

Low back pain is one of the complaints felt by some and almost all postpartum mothers since pregnancy. Low back pain occurs in 45-55% of mothers in the first week postpartum, continues at 8 weeks postpartum as much as 68% and 60% in the next 8 months. Persistent pain causes inhibition of maternal activities and reduces quality of life. One type of complementary therapy is cryotherapy cold therapy with ice. Cold therapy is a therapeutic modality that can absorb tissue temperature so that there is a decrease in tissue temperature through the conduction mechanism. The purpose of this study was to determine the effectiveness of cryoptherapy on low back pain in postpartum mothers during home care during the COVID-19 pandemic. This type of research is a pre-experimental design with One Group Pretest-Posttest with a sample of 22 early postpartum mothers (24 hours to 1 week after delivery). Data were analyzed using paired t test. The results showed that the average pain scale before being given cryotherapy was 6.82 with a standard deviation of 0.907, the average self-efficacy after being given cryotherapy was 3.96 with a standard deviation of 0.64. There was a difference in the mean value between before and after the cryotherapy intervention was given with p-value = 0.002 (p<0.05). It is hoped that health services can use cryotherapy as a therapy to reduce postpartum maternal back pain.

Prospective study for commercial and low-cost hyperspectral imaging systems to evaluate thermal tissue effect on bovine liver samples

Thermal ablation modalities, for example radiofrequency ablation (RFA) and microwave ablation, are intended to prompt controlled tumour removal by raising tissue temperature. However, monitoring the size of the resulting tissue damage during the thermal removal procedures is a challenging task. The objective of this study was to evaluate the observation of RFA on an ex vivo liver sample with both a commercial and a low-cost system to distinguish between the normal and the ablated regions as well as the thermally affected regions. RFA trials were conducted on five different ex vivo normal bovine samples and monitored initially by a custom hyperspectral (HS) camera to measure the diffuse reflectance (Rd) utilising a polychromatic light source (tungsten halogen lamp) within the spectral range 348–950 nm. Next, the light source was replaced with monochromatic LEDs (415, 565 and 660 nm) and a commercial charge-coupled device (CCD) camera was used instead of the HS camera. The system algorithm comprises image enhancement (normalisation and moving average filter) and image segmentation with K-means clustering, combining spectral and spatial information to assess the variable responses to polychromatic light and monochromatic LEDs to highlight the differences in the Rd properties of thermally affected/normal tissue regions. The measured spectral signatures of the various regions, besides the calculation of the standard deviations (δ) between the generated six groups, guided us to select three optimal wavelengths (420, 540 and 660 nm) to discriminate between these various regions. Next, we selected six spectral images to apply the image processing to (at 450, 500, 550, 600, 650 and 700 nm). We noticed that the optimum image is the superimposed spectral images at 550, 600, 650 and 700 nm, which are capable of discriminating between the various regions. Later, we measured Rd with the CCD camera and commercially available monochromatic LED light sources at 415, 565 and 660 nm. Compared to the HS camera results, this system was more capable of identifying the ablated and the thermally affected regions of surface RFA than the side-penetration RFA of the investigated ex vivo liver samples. However, we succeeded in developing a low-cost system that provides satisfactory information to highlight the ablated and thermally affected region to improve the outcome of surgical tumour ablation with much shorter time for image capture and processing compared to the HS system.

Catheter contact angle influences local impedance drop during radiofrequency catheter ablation: insight from a porcine experimental study

Background Local impedance (LI) at a distal tip of the ablation catheter can indirectly measure catheter contact and tissue temperature during radiofrequency catheter ablation (RFCA). LI decreases by RFCA, and a degree of LI drop is correlated with lesion size. However, data on the effects of catheter contact angle on lesion size and LI drop were scarce. This study aimed to evaluate the influence of catheter contact angle on lesion size and LI drop in a porcine experimental study. Methods Lesions were created on porcine myocardial left ventricles by the LI-sensing ablation catheter (IntellaNav MiFi OI®). Contact force (CF) was measured using pressure to current transducer (load cell). Radiofrequency ablation was performed with a power of 30 Watt and a duration of 30 seconds. CF (0g, 5g, 10g, 20g, and 30g) and catheter angle (30°, 45°, and 90°) were changed in each set (total 120 lesions, n=8 each). LI rise, LI drop by RF application, and lesion size (maximum lesion width, maximum surface width, and maximum lesion depth) were evaluated. Results There was no angular dependence in LI rise in all CF. The values of LI rise increased as CF increased. The LI drop also increased as CF increased in all contact angles. Regarding the difference of catheter angles, LI drop with 90° was lower than those with 30° and 45°in CF 10g, 20g, and 30g, respectively. Maximum lesion width and surface width were larger in 30° and 45° than those in 90°, whereas there were no differences in maximum lesion depth. Conclusion LI drop in 90° were significantly lower than those in 45° and 30°. Although lesion depths were not different among the three angles, the absolute values of LI drop were different. Caution should be exercised to comprehend the LI drop with catheter angles. FUNDunding Acknowledgement Type of funding sources: None.