Vagotomy accelerates the onset of symptoms during early disease progression and worsens joint-level pathogenesis in a male rat model of chronic knee osteoarthritis.

Objective: Low vagal tone is common in osteoarthritis (OA) comorbidities and results in greater peripheral inflammation. Characterizing vagal tone's role in OA pathogenesis may offer insights into OA's influences beyond the articular joint. We hypothesized that low vagal tone would accelerate onset of OA-related gait changes and worsen joint damage in a rat knee OA model. Methods: Knee OA was induced in male Sprague Dawley rats by transecting the medial collateral ligament and medial meniscus. Then, left cervical vagus nerve transection (VGX, n â€‹= â€‹9) or sham VGX (non-VGX, n â€‹= â€‹6) was performed. Gait and tactile sensitivity were assessed at baseline and across 12 weeks, with histology and systemic inflammation evaluated at endpoint. Results: At week 4, VGX animals showed limping gait characteristics through shifted stance times from their OA to non-OA limb (p â€‹= â€‹0.055; stance time imbalance â€‹= â€‹1.6 â€‹± â€‹1.6%) and shifted foot strike locations (p â€‹< â€‹0.001; spatial symmetry â€‹= â€‹48.4 â€‹± â€‹0.835%), while non-VGX animals walked with a balanced and symmetric gait. Also at week 4, while VGX animals had a mechanical sensitivity (50% withdrawal threshold) of 13.97 â€‹± â€‹7.70 compared to the non-VGX animal sensitivity of 29.74 â€‹± â€‹9.43, this difference was not statistically significant. Histologically, VGX animals showed thinner tibial cartilage and greater subchondral bone area than non-VGX animals (p â€‹= â€‹0.076; VGX: 0.80 â€‹± â€‹0.036 â€‹mm2; non-VGX: 0.736 â€‹± â€‹0.066 â€‹mm2). No group differences in systemic inflammation were observed at endpoint. Conclusions: VGX resulted in quicker onset of OA-related symptoms but remained unchanged at later timepoints. VGX also had thinner cartilage and abnormal bone remodeling than non-VGX. Overall, low vagal tone had mild effects on OA symptoms and joint remodeling, and not at the level seen in common OA comorbidities.

Wheel Running Exacerbates Joint Damage after Meniscal Injury in Mice, but Does Not Alter Gait or Physical Activity Levels.

PURPOSE: Exercise and physical activity are recommended to reduce pain and improve joint function in patients with knee osteoarthritis (OA). However, exercise has dose effects, with excessive exercise accelerating OA development and sedentary behaviors also promoting OA development. Prior work evaluating exercise in preclinical models has typically used prescribed exercise regimens; however, in-cage voluntary wheel running creates opportunities to evaluate how OA progression affects self-selected physical activity levels. This study aimed to evaluate how voluntary wheel running after a surgically induced meniscal injury affects gait characteristics and joint remodeling in C57Bl/6 mice. We hypothesize that injured mice will reduce physical activity levels as OA develops after meniscal injury and will engage in wheel running to a lesser extent than the uninjured animals. METHODS: Seventy-two C57Bl/6 mice were divided into experimental groups based on sex, lifestyle (physically active vs sedentary), and surgery (meniscal injury or sham control). Voluntary wheel running data were continuously collected throughout the study, and gait data were collected at 3, 7, 11, and 15 wk after surgery. At end point, joints were processed for histology to assess cartilage damage. RESULTS: After meniscal injury, physically active mice showed more severe joint damage relative to sedentary mice. Nevertheless, injured mice engaged in voluntary wheel running at the same rates and distances as mice with sham surgery. In addition, physically active mice and sedentary mice both developed a limp as meniscal injury progressed, yet exercise did not further exacerbate gait changes in the physically active mice, despite worsened joint damage. CONCLUSIONS: Taken together, these data indicate a discordance between structural joint damage and joint function. Although wheel running after meniscal injury did worsen OA-related joint damage, physical activity did not necessarily inhibit or worsen OA-related joint dysfunction or pain in mice.

Wearable Sensing System for NonInvasive Monitoring of Intracranial BioFluid Shifts in Aerospace Applications.

The alteration of the hydrostatic pressure gradient in the human body has been associated with changes in human physiology, including abnormal blood flow, syncope, and visual impairment. The focus of this study was to evaluate changes in the resonant frequency of a wearable electromagnetic resonant skin patch sensor during simulated physiological changes observed in aerospace applications. Simulated microgravity was induced in eight healthy human participants (n = 8), and the implementation of lower body negative pressure (LBNP) countermeasures was induced in four healthy human participants (n = 4). The average shift in resonant frequency was -13.76 ± 6.49 MHz for simulated microgravity with a shift in intracranial pressure (ICP) of 9.53 ± 1.32 mmHg, and a shift of 8.80 ± 5.2097 MHz for LBNP with a shift in ICP of approximately -5.83 ± 2.76 mmHg. The constructed regression model to explain the variance in shifts in ICP using the shifts in resonant frequency (R2 = 0.97) resulted in a root mean square error of 1.24. This work demonstrates a strong correlation between sensor signal response and shifts in ICP. Furthermore, this study establishes a foundation for future work integrating wearable sensors with alert systems and countermeasure recommendations for pilots and astronauts.

Hypertension contributes to exacerbated osteoarthritis pathophysiology in rats in a sex-dependent manner.

BACKGROUND: Hypertension is a common comorbidity of osteoarthritis (OA) with known autonomic dysregulation; thus, the autonomic nervous system may provide a shared underlying mechanism. The objective of this study was to examine the role of the autonomic nervous system in a preclinical model of OA and hypertension. METHODS: Experiments were conducted in spontaneously hypertensive rats and a normotensive control strain, including male and female rats. OA was surgically induced via medial meniscus transection with skin incision used as a sham control (n = 7-8/strain/sex/surgery). Tactile sensitivity, anxiety-related behavior, and serum corticosterone were measured at baseline then bi-weekly across 8 weeks. At weeks 9-10, cardiovascular responses to a chemical vagal nerve agonist were determined to indirectly evaluate vagus nerve function. The joint structure was assessed via grading of histological sections. RESULTS: In males, OA resulted in thinner cartilage in both hypertensive (OA vs. non-OA p < 0.001) and normotensive (OA vs. non-OA p < 0.001). Only females with comorbid hypertension and OA displayed thinner cartilage (p = 0.013). Male hypertensive OA animals had increased calcified subchondral bone compared to normotensive OA animals (p = 0.043) while female hypertensive OA animals had increased calcified subchondral bone compared to hypertensive sham animals (p < 0.001). All MCLT+MMT groups developed low-grade synovitis; interestingly, hypertensive OA females had higher synovitis scores than normotensive OA females (p = 0.046). Additionally, hypertension led to larger drops in blood pressure with vagal activation in both OA (hypertensive vs. normotensive p = 0.018) and sham (hypertensive vs. normotensive p < 0.001) male animals. In females, this trend held true only in OA animals (normotensive vs. hypertensive p = 0.005). CONCLUSION: These data provide preliminary evidence that hypertension influences OA progression and encourages further study into the autonomic nervous system as a possible mechanism.

A Flexible Near-Field Biosensor for Multisite Arterial Blood Flow Detection.

Modern wearable devices show promising results in terms of detecting vital bodily signs from the wrist. However, there remains a considerable need for a device that can conform to the human body's variable geometry to accurately detect those vital signs and to understand health better. Flexible radio frequency (RF) resonators are well poised to address this need by providing conformable bio-interfaces suitable for different anatomical locations. In this work, we develop a compact wearable RF biosensor that detects multisite hemodynamic events due to pulsatile blood flow through noninvasive tissue-electromagnetic (EM) field interaction. The sensor consists of a skin patch spiral resonator and a wearable transceiver. During resonance, the resonator establishes a strong capacitive coupling with layered dielectric tissues due to impedance matching. Therefore, any variation in the dielectric properties within the near-field of the coupled system will result in field perturbation. This perturbation also results in RF carrier modulation, transduced via a demodulator in the transceiver unit. The main elements of the transceiver consist of a direct digital synthesizer for RF carrier generation and a demodulator unit comprised of a resistive bridge coupled with an envelope detector, a filter, and an amplifier. In this work, we build and study the sensor at the radial artery, thorax, carotid artery, and supraorbital locations of a healthy human subject, which hold clinical significance in evaluating cardiovascular health. The carrier frequency is tuned at the resonance of the spiral resonator, which is 34.5 ± 1.5 MHz. The resulting transient waveforms from the demodulator indicate the presence of hemodynamic events, i.e., systolic upstroke, systolic peak, dicrotic notch, and diastolic downstroke. The preliminary results also confirm the sensor's ability to detect multisite blood flow events noninvasively on a single wearable platform.

Strontium isotope analyses of archaeological cremated remains - new data and perspectives.

Cremated human remains are commonly found in the archaeological records, especially in Europe during the Metal Ages and the Roman period. Due to the high temperatures reached during cremation (up to 1000°C), most biological information locked in the isotopic composition of different tissues is heavily altered or even destroyed. The recent demonstration that strontium isotope ratio (87Sr/86Sr) remain unaltered during cremation and are even very resistant to post-burial alterations (which is not the case in unburned bone), opened new possibility for palaeomobility studies of ancient populations that practice cremations as a funerary ritual. This paper summarizes strontium isotopic data produced over the last decade which is then deposited on the open-access platform IsoArcH (https://isoarch.eu/) for any interested parties to use. It is the first time isotopic data on cremated remains is introduced in this database, significantly extending its impact on the scientific community.

Incremental enamel and dentine isotopic data of faunal remains from the United Kingdom.

This paper collates previously published data from incremental isotopic studies performed on faunal remains found within the modern boundaries of the United Kingdom (UK). The dataset represents a complete collection of zooarchaeological incremental data from the UK, consisting of 1,092 data points, obtained from 152 faunal specimens from 20 archaeological sites, dating from 7960 BC to AD 1300. 59 of these values are from incrementally sampled dentine and present stable carbon and nitrogen isotope ratios (δ 13C and δ 15N). The remaining 1,053 values are from incrementally sampled enamel, and present strontium (87Sr/86Sr, n= 193), and/or stable carbon and oxygen isotope ratios (δ 13C and δ 18O, n = 860). This dataset is a convenient resource for future researchers, enabling comparisons based on faunal species, time, and geographical location. Further, the dataset acts as a mechanism for researchers to investigate the variety of incremental sampling methodologies (enamel and dentine) which have been applied to faunal remains across the United Kingdom. For ease of access, this dataset has been deposited on the open-access platform IsoArcH (https://isoarch.eu/).

A Noninvasive, Electromagnetic, Epidermal Sensing Device for Hemodynamics Monitoring.

Non-intrusive monitoring of blood flow parameters is vital for obtaining physiological and pathophysiological information pertaining to dynamic cardiovascular events and is feasible to achieve via non-invasive, conformal, wearable technologies. Here, we present a proof-of-concept of a fully integrated, high frequency (bandwidth 40 MHz), electromagnetic sensing device for monitoring limb hemodynamics and morphology associated with blood flow. The sensing architecture integrates a novel radio frequency (RF) skin patch resonator embedded with a coplanar outer loop antenna and a scalable, standalone wireless readout hardware based on standing wave ratio (SWR) bridge. The resonator itself is a copper-based open circuit planar Archimedean spiral with a rectangular cross-sectional area, chemically etched on a flexible polyimide substrate. The readout hardware is developed exploiting off-the-shelf components, fabricated on the top of a rigid FR4 substrate. The proposed readout circuit can measure resonant frequency of an RLC network. When energized by the external oscillating RF field via loop antenna, the resonator produces an electromagnetic field response which can be perturbed by dielectric variation inside its field boundary. Through leveraging this principle, the in-vitro experimental results from the benchtop models suggest that the resonator's RF attributes such as resonant frequency shift and magnitude variation of reflection coefficient due to fluid volume displacement can be successfully detected through the proposed hardware architecture. Hence, the system could be an alternative to the conventional, multimodal, non-invasive wearable sensing with an unprecedented capability of ubiquitous fluid phenomena detection from multiple sites of the human body.

Passive Self Resonant Skin Patch Sensor to Monitor Cardiac Intraventricular Stroke Volume Using Electromagnetic Properties of Blood.

This paper focuses on the development of a passive, lightweight skin patch sensor that can measure fluid volume changes in the heart in a non-invasive, point-of-care setting. The wearable sensor is an electromagnetic, self-resonant sensor configured into a specific pattern to formulate its three passive elements (resistance, capacitance, and inductance). In an animal model, a bladder was inserted into the left ventricle (LV) of a bovine heart, and fluid was injected using a syringe to simulate stoke volume (SV). In a human study, to assess the dynamic fluid volume changes of the heart in real time, the sensor frequency response was obtained from a participant in a 30° head-up tilt (HUT), 10° HUT, supine, and 10° head-down tilt positions over time. In the animal model, an 80-mL fluid volume change in the LV resulted in a downward frequency shift of 80.16 kHz. In the human study, there was a patterned frequency shift over time which correlated with ventricular volume changes in the heart during the cardiac cycle. Statistical analysis showed a linear correlation [Formula: see text] and 0.87 between the frequency shifts and fluid volume changes in the LV of the bovine heart and human participant, respectively. In addition, the patch sensor detected heart rate in a continuous manner with a 0.179% relative error compared to electrocardiography. These results provide promising data regarding the ability of the patch sensor to be a potential technology for SV monitoring in a non-invasive, continuous, and non-clinical setting.

Non-Invasive Electromagnetic Skin Patch Sensor to Measure Intracranial Fluid-Volume Shifts.

Elevated intracranial fluid volume can drive intracranial pressure increases, which can potentially result in numerous neurological complications or death. This study's focus was to develop a passive skin patch sensor for the head that would non-invasively measure cranial fluid volume shifts. The sensor consists of a single baseline component configured into a rectangular planar spiral with a self-resonant frequency response when impinged upon by external radio frequency sweeps. Fluid volume changes (10 mL increments) were detected through cranial bone using the sensor on a dry human skull model. Preliminary human tests utilized two sensors to determine feasibility of detecting fluid volume shifts in the complex environment of the human body. The correlation between fluid volume changes and shifts in the first resonance frequency using the dry human skull was classified as a second order polynomial with R² = 0.97. During preliminary and secondary human tests, a ≈24 MHz and an average of ≈45.07 MHz shifts in the principal resonant frequency were measured respectively, corresponding to the induced cephalad bio-fluid shifts. This electromagnetic resonant sensor may provide a non-invasive method to monitor shifts in fluid volume and assist with medical scenarios including stroke, cerebral hemorrhage, concussion, or monitoring intracranial pressure.