Noninvasive Alternatives Research Articles

Urinary CC16, a potential indicator of lung integrity and inflammation, increases in children after short-term exposure to PM2.5/PM10 and is driven by the CC16 38GG genotype

Particular matter (PM) exposure is a big hazard for public health, especially for children. Serum CC16 is a well-known biomarker of respiratory health. Urinary CC16 (U-CC16) can be a noninvasive alternative, albeit requiring adequate adjustment for renal handling. Moreover, the SNP CC16 G38A influences CC16 levels. This study aimed to monitor the effect of short-term PM exposure on CC16 levels, measured noninvasively in schoolchildren, using an integrative approach. We used a selection of urine and buccal DNA samples from 86 children stored in an existing biobank. Using a multiple reaction monitoring method, we measured U-CC16, as well as RBP4 (retinol binding protein 4) and β2M (beta-2-microglobulin), required for adjustment. Buccal DNA samples were used for CC16 G38A genotyping. Linear mixed-effects models were used to find relevant associations between U-CC16 and previously obtained data from recent daily PM ≤ 2.5 or 10 μm exposure (PM2.5, PM10) modeled at the child's residence. Our study showed that exposure to low PM at the child's residence (median levels 18.9 μg/m³ (PM2.5) and 23.6 μg/m³ (PM10)) one day before sampling had an effect on the covariates-adjusted U-CC16 levels. This effect was dependent on the CC16 G38A genotype, due to its strong interaction with the association between PM levels and covariates-adjusted U-CC16 (P = 0.024 (PM2.5); P = 0.061 (PM10)). Only children carrying the 38GG genotype showed an increase of covariates-adjusted U-CC16, measured 24h after exposure, with increasing PM2.5 and PM10 (β = 0.332; 95% CI: 0.110 to 0.554 and β = 0.372; 95% CI: 0.101 to 0.643, respectively). To the best of our knowledge, this is the first study using an integrative approach to investigate short-term PM exposure of children, using urine to detect early signs of pulmonary damage, and taking into account important determinants such as the genetic background and adequate adjustment of the measured biomarker in urine.

Impedance-based non-invasive assay for ocular damage prediction on in vitro 3D reconstructed human corneal epithelium

Reconstructed human cornea-like epithelium (RhCE) holds unprecedented promise for toxicological analyses and the replacement of animal use. However, current standards to evaluate potential ocular irritancy present a major downfall, the need to invasively alter tissue samples to evaluate cell viability. In this study, the applicability of impedance analysis was validated by monitoring the change in cell capacitance during tissue maturation and before and after chemical application using coupled electrodes. Our results indicate that cell maturation on RhCE models can be evaluated during model production using capacitance sensing offering a faster and simpler quality control criteria for RhCE model usability. Additionally, cell capacitance resulted to be more sensitive in detecting slight cell damages than methods based on cell metabolism, and when integrated into OECD-approved testing strategies, capacitance sensing performed as good as currently accepted methodologies displaying 66% sensitivity, 100% specificity and 83% accuracy when evaluated at 300 Hz. In summary, a quantitative analysis to predict in vivo ocular irritation based on changes in RhCE capacitance by impedance spectroscopy is suggested. This methodology represents a non-invasive and non-destructive alternative that would enable the monitoring of reversible effects or repeated dose toxicity.

Non-invasive biomarkers and FIB-4, APRI scoring system to rule out advanced liver injury

Chronic liver Injury (CLI) and its end-stages, cirrhosis, and hepatocellular carcinoma (HCC), are leading causes of morbidity and mortality worldwide with enormous socioeconomic costs. Clinical management of chronic liver injury is dependent on the extent of liver fibrosis. Liver biopsy, the gold standard, is still recommended in most patients. Liver disease diagnosis can generally be made using a carefully obtained history, physical examination, and a few laboratory tests. Initial laboratory testing should include aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin. Biomarkers are being developed as alternatives to liver biopsy for predicting liver fibrosis, Cirrhosis and HCC in patients with chronic liver injury. An intensive research on non-invasive alternatives. A simple, reproducible, low-cost, and non-invasive tool that can follow the evolution of the disease overtime would be beneficial for the testing physician and is desired by the patients. The aim of this review is to summarize Non-Invasive Biomarkers in addition to score systems like FIB-4 and (Aspartate Platelet Ratio Index) APRI in assessment of Fibrosis, Cirrhosis and HCC.

Parametric Tracking of Electrical Current Components Using Gradient Descent Algorithm

In the last few years, Motor Current Signature Analysis (MCSA) has proven to be an effective method for electrical machines condition monitoring. Indeed, compared to vibration and temperature analysis, current measurement proves to be a convenient and non-invasive alternative. Moreover, it has proven to be a reliable method since many mechanical and electrical faults manifest as side-band spectral components generated around the fundamental frequency component of the motor’s current. These components are called interharmonics and they are a major focus of fault detection using MCSA. However, the main drawback of this approach is that the interference of other more prevalent components such as the fundamental and noise components can obstruct the effect of interharmonics in the spectrum and may therefore affect fault detection accuracy. Thus, we propose in this paper an alternative approach that aims to decompose the different current components using a model based on a Vandermonde matrix, in order to monitor each component independently. Then, the tracking of each distinct component in time and spectral domains is implemented. This is achieved by estimating their respective relevant parameters using the Gradient Descent algorithm. This method has been favorably compared to an existing estimation algorithm (MUSIC) and its efficiency has been validated. The results of this work prove to be promising and establish the parametric tracking of the electrical current components using the Gradient Descent algorithm as a reliable monitoring approach.

Infrared cavity ring-down spectroscopy for detecting non-small cell lung cancer in exhaled breath

Early diagnosis of lung cancer greatly improves the likelihood of survival and remission, but limitations in existing technologies like low-dose computed tomography have prevented the implementation of widespread screening programs. Breath-based solutions that seek disease biomarkers in exhaled volatile organic compound (VOC) profiles show promise as affordable, accessible and non-invasive alternatives to traditional imaging. In this pilot work, we present a lung cancer detection framework using cavity ring-down spectroscopy (CRDS), an effective and practical laser absorption spectroscopy technique that has the ability to advance breath screening into clinical reality. The main aims of this work were to (1) test the utility of infrared CRDS breath profiles for discriminating non-small cell lung cancer (NSCLC) patients from controls, (2) compare models with VOCs as predictors to those with patterns from the CRDS spectra (breathprints) as predictors, and (3) present a robust approach for identifying relevant disease biomarkers. First, based on a proposed learning curve technique that estimated the limits of a model’s performance at multiple sample sizes (10–158), the CRDS-based models developed in this work were found to achieve classification performance comparable or superior to like mass spectroscopy and sensor-based systems. Second, using 158 collected samples (62 NSCLC subjects and 96 controls), the accuracy range for the VOC-based model was 65.19%–85.44% (51.61%–66.13% sensitivity and 73.96%–97.92% specificity), depending on the employed cross-validation technique. The model based on breathprint predictors generally performed better, with accuracy ranging from 71.52%–86.08% (58.06%–82.26% sensitivity and 80.21%–88.54% specificity). Lastly, using a protocol based on consensus feature selection, three VOCs (isopropanol, dimethyl sulfide, and butyric acid) and two breathprint features (from a local binary pattern transformation of the spectra) were identified as possible NSCLC biomarkers. This research demonstrates the potential of infrared CRDS breath profiles and the developed early-stage classification techniques for lung cancer biomarker detection and screening.

Waveform Morphology as a Surrogate for ICP Monitoring: A Comparison Between an Invasive and a Noninvasive Method.

BackgroundAlthough the placement of an intraventricular catheter remains the gold standard technique for measuring intracranial pressure (ICP), the method has several limitations. Therefore, noninvasive alternatives to ICP (ICPni) measurement are of great interest. The main objective of this study was to compare the correlation and agreement of wave morphology between ICP (standard intraventricular ICP monitoring) and a new ICPni monitor in patients admitted with stroke. The second objective was to estimate the discrimination of the noninvasive method to detect intracranial hypertension.MethodsWe prospectively collected data of adults admitted to an intensive care unit with subarachnoid hemorrhage, intracerebral hemorrhage, or ischemic stroke in whom an invasive ICP monitor was placed. Measurements were simultaneously collected from two parameters [time-to-peak (TTP) and the ratio regarding the second and first peak of the ICP wave (P2/P1 ratio)] of ICP and ICPni wave morphology monitors (Brain4care). Intracranial hypertension was defined as an invasively measured sustained ICP > 20 mm Hg for at least 5 min.ResultsWe studied 18 patients (subarachnoid hemorrhage = 14; intracerebral hemorrhage = 3; ischemic stroke = 1) on 60 occasions with a median age of 52 ± 14.3 years. A total of 197,400 waves (2495 min) from both ICP (standard ICP monitoring) and the ICPni monitor were sliced into 1-min-long segments, and we determined TTP and the P2/P1 ratio from the mean pulse. The median invasively measured ICP was 13 (9.8–16.2) mm Hg, and intracranial hypertension was present on 18 occasions (30%). The correlation and agreement between invasive and noninvasive methods for wave morphology were strong for the P2/P1 ratio and moderate for TTP using categoric (κ agreement 88.1% and 71.3%, respectively) and continuous (intraclass correlation coefficient 0.831 and 0.584, respectively) measures. There was a moderate but significant correlation with the mean ICP value (P2/P1 ratio r = 0.427; TTP r = 0.353; p < 0.001 for all) between noninvasive and invasive techniques. The areas under the curve to estimate intracranial hypertension were 0.786 [95% confidence interval (CI) 0.72–0.93] for the P2/P1 ratio and 0.694 (95% CI 0.60–0.74) for TTP.ConclusionsThe new ICPni wave morphology monitor showed a good agreement with the standard invasive method and an acceptable discriminatory power to detect intracranial hypertension.Clinical trial registration Trial registration: NCT05121155.

Restorative Exercise Models in Dysphagia and Obstructive Sleep Apnea: A Review

<h3>Objective(s)</h3> Restorative dysphagia exercise approaches hold merit in research and practice within speech-language pathology given strong evidence for targeted interventions leading to improved deglutition. Restorative exercise approaches for obstructive sleep apnea (OSA) share common anatophysiologic bases with dysphagia; however, have received limited scientific attention to establish their utility as non-invasive treatment alternatives for OSA. Researchers' primary aim was to provide a summary of the current state-of-science on the biomechanics of OSA with a summary of therapeutic targets relative to muscle physiology. A secondary aim was assessing the physiologic adaptations following restorative dysphagia exercise relative to exercise models for treatment of OSA for comparative analysis. Clinical research and scope-of-practice implications of exercise benefits reflected in similar biomechanical profiles and muscular adaptations in OSA and dysphagia are discussed. <h3>Data Sources</h3> Literature was identified using hand-searched and database-driven methods from PubMed, Google Scholar, and Medline. <h3>Study Selection</h3> (1) systematic reviews/meta-analysis; (2) author(s) quantified measures of article strengths/weaknesses; (3) published after 2011; (4) available in English. <h3>Data Extraction</h3> Authors independently assessed articles for eligibility and evidence strength using The Scottish Intercollegiate Guidelines Network (SIGN) tool. Average SIGN ratings across intervention categories were obtained. <h3>Data Synthesis</h3> Study results were categorized and assessed for strength of evidence with SIGN and conclusions on therapeutic targets and the physiologic adaptations relative to specific targets. A majority of studies were systematic reviews and meta-analyses. Researchers identified sources of variation and consistency in outcome measures across studies, leading to a quantitative and qualitative synthesis of findings within dysphagia and OSA outcome measures. <h3>Conclusions</h3> Preliminary findings point to potential adjuvant treatment avenues in some patients with OSA and potential co-recruitment of OSA-related muscles during restorative dysphagia exercises. Findings point to common therapeutic targets and anatophysiologic goals within dysphagia and OSA exercise interventions. <h3>Author(s) Disclosures</h3> Nicholas Stocker is first author, Laura L.O. Froeschke is second author, Raymond Kraus is third author.

ROLE OF COLOR DOPPLER ULTRASONOGRAPHY IN THE EVALUATION OF PORTAL VENOUS HYPERTENSION

Chronic alcoholism, obesity and viral hepatitis (B &amp; C virus) are main causes for chronic liver disease. In cirrhotic patients, portal hypertension and its complications lead to signicant morbidity and mortality. Ultrasound technique, such as duplex ultrasonography ,spectral and color Doppler imaging are the modalities of choice. Study was undertaken to evaluate spectrum of color Doppler sonographic ndings in portal hypertension, to study ow metric changes in portal hypertension and to look for presence of various Porto-systemic collaterals. Result of study shows alcoholic liver disease as the main cause for liver cirrhosis. Maximum number of patients with splenorenal collaterals. Color Doppler sonography is a valuable non-invasive alternative which provides precise information in localizing and characterizing portal vein in patients with portal hypertension and identify the presence of various Porto-systemic collaterals. The hepatic vein damping index (DI) correlates well with the severity of liver dysfunction in terms of Child Pugh score.

Is 3-Dimensional Scanning Really Helpful in Implant-Based Breast Reconstruction?: A Prospective Study.

Breast reconstruction is an integral part of breast cancer treatment, and implant-based breast reconstruction is the most commonly used method worldwide. However, there is still no technique that allows surgeons to predict the volume of the required implant. Although computed tomography and magnetic resonance imaging provide adequate representations of the breast, these procedures are time-consuming, expensive, and expose patients to radiation. Therefore, there is a need for safer, noninvasive alternatives for preoperative breast volume measurements. This study is a prospective review of 12 patients with early-stage breast cancer who underwent nipple-sparing mastectomy and immediate breast reconstruction with implants. Preoperatively, the Artec Eva 3D scanner was used to acquire volumetric measurements of the breasts. Intraoperatively, the volume of the mastectomy specimen was measured using the water displacement method. Correlations among the preoperative breast, mastectomy specimen, and estimated and final implant volumes were analyzed through Pearson correlation coefficient. A correction prediction factor of 85% was applied where necessary. Patient and physician satisfaction were evaluated 3 months postoperatively. Our study found a statistically significant correlation between the preoperative breast volumes measured by the Artec Eva 3D scanner and intraoperative mastectomy specimen volumes (r = 0.6578). There was no correlation between the preoperative breast volumes and final implant volumes, mastectomy specimen volumes and final implant volumes, and estimated implant volumes and final implant volumes. Although the Artec Eva 3D scanner can offer relatively accurate measurement of breast volumes, multiple studies still need to be done to determine how these data can be applied to the mastectomy procedure and breast implant selection. It may be more applicable for preoperative planning in breast augmentation surgery. Future surgeons should also take into account that variabilities in natural breast size, tumor size, cancer stage, and in patient and physician preferences all influence the outcome of breast reconstruction surgery.

First Experience with the Munich Valsalva Implantation Technique (MuVIT) for Cardiac Output Reduction During Standard and Complex Thoracic Endovascular Aortic Repair

The Munich Valsalva Implantation Technique (MuVIT) is a non-invasive alternative which uses a modified Valsalva manoeuvre to reduce cardiac output (CO). The aim of this study was to evaluate the technical success and safety of MuVIT in standard and complex endovascular thoracic aneurysm repair (TEVAR). This was a retrospective single centre cohort study. Patients were included who underwent CO reduction with MuVIT between March 2020 and February 2021 for standard and fenestrated/branched TEVAR (fbTEVAR). The target systolic blood pressure (SBP) reduction was used as an indicator of CO reduction. The aim of the SBP reduction was 50% in patients undergoing proximal sealing in Ishimaru zones 0-1 (Group 1), and 30% in patients with sealing in Ishimaru zones 2-3 (Group 2). Efficacy outcomes included MuVIT technical success and procedural technical success. Safety outcomes included MuVIT and procedural related complications in the first 30 days. During the study period 52 cases were screened for MuVIT. Of these, 40 patients (77%) underwent procedures that were performed under MuVIT. Exclusion reasons were local anaesthesia (n= 9); pulmonary contraindications (n= 2), and poor heart pump function (n= 1). Fifteen patients (37.5%) underwent bTEVAR, three patients (7.5%) fTEVAR, and 22 patients (55%) standard TEVAR. Twenty nine (72.5%) procedures were elective, seven (17.5%) were urgent, and four (10%) were as an emergency. Successful proximal endograft deployment under MuVIT was 100%. The target SBP reduction was achieved in 95% (Group 1: 89.5%, Group 2: 100%), with an overall mean reduction of 46% (Group 1: 55%, Group 2: 40%). The 30 day mortality was 7.5%, and was not MuVIT related. Two patients with COPD Gold III/IV developed respiratory complications. MuVIT is a safe and effective manoeuvre for CO reduction during aortic arch TEVAR. However, careful patient selection is required and potential adverse effects on patients with severe COPD needs further evaluation.

Implementation of advanced radiotherapy techniques: stereotactic body radiotherapy (SBRT) for oligometastatic patients with lung metastasis - a single institution experience.

The treatment of oligometastatic disease has become common practice as advanced radiotherapy techniques became more available. Lung is one of the main metastatic sites for a majority of cancers and many of these patients present with a limited metastatic disease burden. For these patients, SBRT (Stereotactic Body Radiation Therapy) represents a non-invasive treatment alternative. In this report we present our experience with our first series of patients with limited metastatic disease treated with lung SBRT. The purpose of this paper is to provide a qualitative and quantitative assessment of the lung SBRT treatment process and algorithm leading up to treatment delivery in a community-based radiotherapy department. We have retrospectively reviewed our first series of 41 patients with lung oligometastases from various malignancies, treated using SBRT between March 2019 and December 2020. Demographic, technical and outcome data were analyzed. A number of 45 lung metastases (in 41 patients) were treated with SBRT during the specified time period. The median age was 65.7 years old (range 33-83). 16 patients (39%) were treated for multiple lesions and the mean number of treated lesions was 1 (range1-3). Median dose prescribed was 50 Gy /5 fractions (median BED10 =77 Gy). The median intra-fraction displacements were: Vertical (0.23cm), Longitudinal (-0.27 cm), Lateral (-0.1 cm), Pitch [0.22°], Roll [0.15°], Rotation [0.32°]. The median session time was 40 minutes. All patients completed the prescribed course of treatment.Preliminary clinical data were recorded. With a median follow-up of 9 months, local control was recorded in all but one patient. At the last known follow-up, local control was recorded for 39 (85%) out of 45 treated lesions. For lung SBRT, the required corrections at the time of treatment delivery are small, as long as strict protocols are implemented. Preliminary data for lung metastasis in oligometastatic patients support SBRT as a viable method of achieving high rates of early local control. These results need to be further confirmed in a larger cohort of patients with longer follow-up.

Translaryngeal ultrasound in thyroid surgery: state of the art review.

Clinical voice assessment prior to thyroid and parathyroid surgery is essential, but the paradigm of indirect laryngoscopy (IDL), when indicated, has been challenged by the risk of aerosolised SARS-Cov-2 during endoscopy of the aerodigestive tract. Translaryngeal ultrasound (TLUS) to assess the vocal cords has been proposed as a safe, non-invasive and sensitive alternative. The aim of this review was to verify TLUS as a viable tool for perioperative laryngeal assessment. A literature review was performed using Medline, Embase, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials and Scopus with the following search strategy: (vocal cord OR vocal fold OR glottic OR glottis OR vocal ligaments OR rima glottidis) AND (ultras* OR sonograph* OR echography OR echotomography). Fifteen studies were included in this review. All studies compared TLUS to IDL in visualizing the vocal cords in adults. Ten studies compared pre-operative TLUS to IDL where 50.6-100% of vocal cords were successfully visualized. Nine studies compared post-operative TLUS to IDL and reported visualization between 39.6% and 100%. Pre- and post-operative negative predictive values ranged from 60% to 100%. Whilst promising, successful visualization of the cords is limited by inter-user variability, older age and male gender. Thus, we see the role of TLUS as an alternative to IDL in the post-operative setting in the young patient following uncomplicated surgery with a normal voice on clinical examination, to confirm recurrent laryngeal nerve integrity while minimizing the risk of aerosolization.

P335 Utility of Intestinal Ultrasound in Monitoring Disease Activity in Ulcerative Colitis Patients Treated with Biologics

Abstract Background Given the invasive nature and high cost of frequent and repeated endoscopies needed to monitor UC, search for non-invasive diagnostic alternative is warranted. Intestinal ultrasound is a cost-effective, well-tolerated, non-invasive and readily available „point-of-care“ tool for the management of patients with Crohn’s disease. The role and widespread use of IUS for UC is still limited. We aimed to evaluate association between UC disease activity assessed by IUS on one hand and standard clinical, biochemical, and endoscopic parameters on the other one. Methods A single center, noninterventional retrospective chart review of adult UC patients treated with biologics at a tertiary center was performed. Routine clinical (stool frequency score – SFS, and rectal bleeding score – RBS), biochemical (FC), endoscopic (Mayo Endoscopic Subscore - MES), and IUS parameters (bowel wall thickness - BWT and colonic wall hyperemia assessed by colour Doppler imaging - CDS) were assessed before initiating biologics. Normal distribution was assessed using Shapiro-Wilk tests. Spearman correlation coefficients were calculated and ROC analysis was carried out. Results Total of, 44 patients (50% females, mean age, 37.4 ±, 14.05 years) with predominantly extensive UC (75%) were analysed. Positive correlation was observed between combination of BWT and level of CDS with SFS (rs = 0.68, p &amp;lt;, 0.01, N = 33) as well as with RBS (rs = 0.44, p &amp;lt;, 0.01, N = 34). Moreover FC values were in positive correlation with BWT (rs = 0.54, p &amp;lt;, 0.01, N = 36), levels of CDS (rs = 0.66, p &amp;lt;, 0.01, N = 33) and combination of BWT coupled with level of CDS (rs = 0.7, p &amp;lt;, 0.01, N = 33). In case of clinical active UC (SFS, 2/3 + RBS, 2/3 + FC &amp;gt;150 mg/g) correlation coefficient between FC level and BWT coupled with level of CDS rises to rs = 0.72, p &amp;lt;, 0.01, N = 30. Positive correlation of CDS with MES (rs = 0.65, p &amp;lt;, 0.01, N = 16) as well as between combination of BWT + level of CDS with MES (rs = 0.6, p &amp;lt;, 0.02, N = 16) was observed. Interestingly, positive correlation between BWT and MES didn′t reach statistical significance (rs = 0.42, p = 0.1, N = 16). The area under the curve (AUC) for the FC values and disease activity (defined as SFS, 2/3 + RBS, 2/3 + BWT &amp;gt;4 mm + presence of CDS) was, 0.96 (SE:, 0.03;, 95% CI, 0.89–0.99, p&amp;lt;0.01). FC values &amp;gt;134 mg/g were associated with active disease (sensitivity, 89.3%, specificity, 87.5%). Conclusion Results of this study show a good correlation between IUS and clinical, biochemical and endoscopic parameters of UC disease severity. IUS as a monitoring tool can be helpful in estimation of UC disease activity and can guide daily management of patients treated with biologics.

Non-Invasive Assessment of Mild Stress-Induced Hyperthermia by Infrared Thermography in Laboratory Mice.

Simple SummaryStressful events can trigger body temperature variations in mammals. The most commonly used methods for measuring temperature in laboratory mice are stressful and invasive in nature, and can themselves cause stress-induced hyperthermia (SIH). This raises concerns regarding both animal welfare and research output. Infrared thermography (IRT) offers a non-invasive alternative, if proven to accurately identify SIH. We exposed mice to mild handling-induced stress, by either tail-picking or the reportedly less-impactful tunnel-handling technique. Temperature was measured by reading microchip devices (PIT-tags) implanted subcutaneously (Tsc), and by a thermal camera to measure mean body surface temperature (Tbody) and mean tail surface temperature (Ttail). As expected, during acute stress exposure, both Tsc and Tbody increased, while Ttail decreased. No differences in stress-induced hyperthermia were found between the two handling techniques. This suggests that such differences may not be detectable in the context of co-occurring stressful events, such as opening of the cage lid, exposure to light, or presence of the handler. Within the same cage, animals handled last consistently showed higher body temperatures than those handled first, raising the issue of minding the order by which animals are tested. Our results suggest IRT offers a reliable non-invasive method for assessing SIH in laboratory rodents.Stress-induced hyperthermia (SIH) is a physiological response to acute stressors in mammals, shown as an increase in core body temperature, with redirection of blood flow from the periphery to vital organs. Typical temperature assessment methods for rodents are invasive and can themselves elicit SIH, affecting the readout. Infrared thermography (IRT) is a promising non-invasive alternative, if shown to accurately identify and quantify SIH. We used in-house developed software ThermoLabAnimal 2.0 to automatically detect and segment different body regions, to assess mean body (Tbody) and mean tail (Ttail) surface temperatures by IRT, along with temperature (Tsc) assessed by reading of subcutaneously implanted PIT-tags, during handling-induced stress of pair-housed C57BL/6J and BALB/cByJ mice of both sexes (N = 68). SIH was assessed during 10 days of daily handling (DH) performed twice per day, weekly voluntary interaction tests (VIT) and an elevated plus maze (EPM) at the end. To assess the discrimination value of IRT, we compared SIH between tail-picked and tunnel-handled animals, and between mice receiving an anxiolytic drug or vehicle prior to the EPM. During a 30 to 60 second stress exposure, Tsc and Tbody increased significantly (p < 0.001), while Ttail (p < 0.01) decreased. We did not find handling-related differences. Within each cage, mice tested last consistently showed significantly higher (p < 0.001) Tsc and Tbody and lower (p < 0.001) Ttail than mice tested first, possibly due to higher anticipatory stress in the latter. Diazepam-treated mice showed lower Tbody and Tsc, consistent with reduced anxiety. In conclusion, our results suggest that IRT can identify and quantify stress in mice, either as a stand-alone parameter or complementary to other methods.

Cross-Sectional Imaging Instead of Colonoscopy in Inflammatory Bowel Diseases: Lights and Shadows.

International guidelines recommend a treat-to-target strategy with a close monitoring of disease activity and therapeutic response in inflammatory bowel diseases (IBD). Colonoscopy (CS) represents the current first-line procedure for evaluating disease activity in IBD. However, as it is expensive, invasive and poorly accepted by patients, CS is not appropriate for frequent and repetitive reassessments of disease activity. Recently, cross-sectional imaging techniques have been increasingly shown as reliable tools for assessing IBD activity. While computed tomography (CT) is hampered by radiation risks, routine implementation of magnetic resonance enterography (MRE) for close monitoring is limited by its costs, low availability and long examination time. Novel magnetic resonance imaging (MRI)-based techniques, such as diffusion-weighted imaging (DWI), can overcome some of these weaknesses and have been shown as valuable options for IBD monitoring. Bowel ultrasound (BUS) is a noninvasive, highly available, cheap, and well accepted procedure that has been demonstrated to be as accurate as CS and MRE for assessing and monitoring disease activity in IBD. Furthermore, as BUS can be quickly performed at the point-of-care, it allows for real-time clinical decision making. This review summarizes the current evidence on the use of cross-sectional imaging techniques as cost-effective, noninvasive and reliable alternatives to CS for monitoring patients with IBD.

Temporal Trends in Diagnostic Testing Patterns for Wild-Type Transthyretin Amyloid Cardiomyopathy in the Medicare Fee-for-Service Population

Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is frequently misdiagnosed or diagnosed late in the disease course. ATTRwt-CM can be diagnosed invasively through tissue biopsy, but current diagnostic recommendations indicate technetium-99m pyrophosphate (99mTc-PYP) bone scintigraphy is an acceptable noninvasive alternative. The relative use of these confirmatory diagnostic tests in routine clinical practice is unknown. A retrospective observational study assessed temporal trends in biopsy and 99mTc-PYP scintigraphy and differences in patient characteristics using in/outpatient claims data from the US Medicare fee-for-service database. Claims prevalence for biopsy alone (≥1 claim for cardiac/extracardiac biopsy), imaging alone (≥1 claim for 99mTc-PYP scintigraphy), and both tests and patient demographic, geographic, and clinical characteristics were examined. Of patients (n=1226) receiving an ATTRwt-CM diagnostic code, 29%, 47%, and 24% were diagnosed by biopsy alone, 99mTc-PYP scintigraphy alone, and both tests, respectively. Patients with claims for 99mTc-PYP scintigraphy alone were older than those with claims for biopsy alone (79.9 vs 76.5; p <0.001). Fewer patients in the southern United States and more patients in the northeastern United States had claims for 99mTc-PYP scintigraphy alone than biopsy alone (p <0.001). There was a temporal trend toward more claims for 99mTc-PYP scintigraphy alone (odds ratio 1.21; p <0.001) and both tests (odds ratio 1.10; p=0.008) versus biopsy alone. From 2017 to 2019, claims increased for 99mTc-PYP scintigraphy alone. In conclusion, these data suggest a growing preference for the noninvasive imaging technique, which has high sensitivity/specificity, usability, and accessibility and may help facilitate earlier disease diagnosis. United States regional differences in the use of 99mTc-PYP scintigraphy highlight the need for education initiatives.

Prostate cancer detection: a systematic review of urinary biosensors.

Current diagnostic methods for prostate cancer are invasive and lack specificity towards aggressive forms of the disease, which can lead to overtreatment. A new class of non-invasive alternatives is under development, in which urinary biomarkers are detected using biosensing devices to offer rapid and accurate prostate cancer diagnosis. These different approaches are systematically reviewed and their potential for translation to clinical practice is evaluated. A systematic review of the literature was performed in May 2021 using PubMed Medline database, Embase, and Web of Science. The objective was to review the structural designs and performance of biosensors tested on urine samples from patients with prostate cancer. A total of 76 records were identified. After screening and eligibility, 14 articles were included and are discussed in this paper. The biosensors were discussed based on the target biomarkers and detection technologies used, as well as the results of the clinical studies. Most of the works reported good discrimination between patients with prostate cancer and controls. This review highlights the potential of urinary biosensors for non-invasive prostate cancer detection. However, clinical studies have so far only been conducted on small cohorts of patient, with large scale trials still needed to validate the proposed approaches. Overall, the consensus arising from the proof of concepts studies reviewed here, is that an adequate combination of biomarkers into multiplex biosensor platforms is required to achieve accurate diagnostic tests. Furthermore, whether such devices can discriminate between aggressive and indolent cancer has not yet been addressed, because it entails optimized biomarkers panels and long-term clinical trials.

Electrical Impedance of Surface Modified Porous Titanium Implants with Femtosecond Laser.

The chemical composition and surface topography of titanium implants are essential to improve implant osseointegration. The present work studies a non-invasive alternative of electrical impedance spectroscopy for the characterization of the macroporosity inherent to the manufacturing process and the effect of the surface treatment with femtosecond laser of titanium discs. Osteoblasts cell culture growths on the titanium surfaces of the laser-treated discs were also studied with this method. The measurements obtained showed that the femtosecond laser treatment of the samples and cell culture produced a significant increase (around 50%) in the absolute value of the electrical impedance module, which could be characterized in a wide range of frequencies (being more relevant at 500 MHz). Results have revealed the potential of this measurement technique, in terms of advantages, in comparison to tiresome and expensive techniques, allowing semi-quantitatively relating impedance measurements to porosity content, as well as detecting the effect of surface modification, generated by laser treatment and cell culture.

Paraquat sorption- and organic matter-induced modifications of soil spectral induced polarization (SIP) signals

SUMMARY Quantifying the capacity of soils to immobilize sorbing contaminants of concern relies on batch sorption experiments, typically performed at skewed solid-to-liquid ratios. The geophysical method spectral induced polarization (SIP) provides a powerful non-invasive monitoring alternative that can capture changes in soil electrical properties driven by contaminant sorption, yielding an approach whereby immobilization can be monitored in situ. Here, we present SIP signals obtained from a series of columns packed with a water saturated natural sandy-loam soil, with and without solid organic matter (SOM) amendment, contaminated with increasing concentrations of the herbicide paraquat. Our results highlight that soil polarization drops proportional to increasing amounts of sorbed paraquat in the SOM-free soil, exhibiting a Langmuir-type leveling-off behaviour. The addition of 8 percent-SOM yielded an increase in both the real ($\sigma ^{\prime}$) and imaginary ($\sigma ^{\prime\prime}$) conductivity of the uncontaminated treatment, driven by the contribution of charged sites in the SOM. Further, SOM modified the dependence between $\sigma ^{\prime\prime}$ and sorbed paraquat, likely driven by continued polarization within the polydisperse SOM with continued paraquat addition. However, the time constant ($\tau $), derived using the Cole–Cole model, shed light on a saturation-type dependence governed by a drop in ion mobility with increasing sorption. Thus, aiding the interpretation of sorption-driven SIP signals.

A technical and data analytic approach to pressure-volume loops over numerous cardiac cycles

Cardiac pressure-volume (PV) loop analysis is the reference standard for studying the cardiovascular implications of clinical perturbations (eg, heart failure, aortic occlusion, hypovolemia) and is a benchmark for comparisons with noninvasive alternatives (eg, ultrasound, magnetic resonance imaging). Historically, most PV loop analyses were of individual cardiac cycles for which the options to analyze PV loops using off-the-shelf software were limited, and home-grown analysis software often lacked peer review or code-sharing. Our aim was to describe a start-to-finish implementation of PV loops for determination of hemodynamic parameters in swine, to provide technical advice for vascular access and proceduralization, and to describe data capture, curation, preprocessing, and analysis of raw PV time data. We have provided a novel data analytic method to programmatically analyze raw PV loop data beyond single cardiac cycles and real, raw swine PV loop data and the accompanying MATLAB (MathWorks, Inc, Natick, Mass) code as an example of how to process and analyze raw data directly.