Studies In Human Subjects Research Articles

Gut Microbiota and Gut–Brain Axis in Hypertension: Implications for Kidney and Cardiovascular Health—A Narrative Review

Introduction: Arterial hypertension is a major contributor to a wide range of health complications, with cardiac hypertrophy and chronic kidney disease being among the most prevalent. Consequently, novel strategies for the treatment and prevention of hypertension are actively being explored. Recent research has highlighted a potential link between hypertension and the gut–brain axis. A bidirectional communication between the microbiota and the brain via the vagus nerve, enteric nervous system, hypothalamus–pituitary–adrenal axis, secreted short-chain fatty acids, and neurotransmitter metabolism. Materials and methods: A comprehensive literature search was conducted using databases such as PubMed to identify studies exploring the relationship between gut microbiota and hypertension, along with the effects of dietary interventions and probiotics on blood pressure regulation. Discussion: Studies in both animal models and human subjects have demonstrated a strong correlation between alterations in gut microbiota composition and the development of hypertension. By influencing blood pressure, the gut microbiota can potentially affect the progression of cardiovascular and kidney disorders. Modulating gut microbiota through dietary interventions and probiotics has shown promise in regulating blood pressure and reducing systemic inflammation, offering a novel approach to managing hypertension. Diets such as the Mediterranean diet, which is rich in polyphenols and omega-3 fatty acids and low in sodium, promote the growth of beneficial gut bacteria that support cardiovascular health. Additionally, probiotics have been found to enhance gut barrier function, reduce inflammation, and modulate the Renin–Angiotensin System, all of which contribute to lowering blood pressure. Conclusions: Further research is needed to determine the mechanisms of action of the microbiota in hypertension. The aim of this study was to evaluate the influence of gut microbiota on blood pressure regulation and the progression of hypertension-related complications, such as cardiovascular and kidney disorders.

Feasibility of PET-enabled dual-energy CT imaging: First physical phantom and initial patient study results.

Dual-energy (DE) CT enables material decomposition by using two different x-ray energies and may be combined with PET for improved multimodality imaging. However, this increases radiation dose and may require a hardware upgrade due to the added second x-ray CT scan. The recently proposed PET-enabled DECT method allows dual-energy imaging using a conventional PET/CT scanner without the need to change scanner hardware or increase radiation exposure. Here we demonstrate the first-time physical phantom and patient data evaluation of this method. The PET-enabled DECT method reconstructs a gamma-ray CT (gCT) image at 511keV from the time-of-flight PET data with the maximum-likelihood attenuation and activity (MLAA) approach and then combines this image with the low-energy x-ray CT images to form a dual-energy image pair for material decomposition. To improve the image quality of gCT, a kernel MLAA method was developed using the x-ray CT as a priori information. Here we developed a general open-source implementation for gCT reconstruction and used this implementation for the first real data validation using both physical phantom study and human-subject study. Results from PET-enabled DECT were compared using x-ray DECT as the reference. Further, we applied the PET-enabled DECT method in another patient study to evaluate bone lesions. Compared to the standard MLAA, results from the kernel MLAA showed significantly improved image quality. PET-enabled DECT with the kernel MLAA was able to generate fractional images that were comparable to the x-ray DECT, with high correlation coefficients for both the phantom study and human subject study (R > 0.99). The application study also indicates that PET-enabled DECT has potential to characterize bone lesions. Results from this study have demonstrated the feasibility of this PET-enabled method for CT imaging and material decomposition. PET-enabled DECT shows promise to provide comparable results to x-ray DECT.

Label-Free Subjective Player Experience Modelling via Let's Play Videos

Player Experience Modelling (PEM) is the study of AI techniques applied to modelling a player's experience within a video game. PEM development can be labour-intensive, requiring expert hand-authoring or specialized data collection. In this work, we propose a novel PEM development approach, approximating player experience from gameplay video. We evaluate this approach predicting affect in the game Angry Birds via a human subject study. We validate that our PEM can strongly correlate with self-reported and sensor measures of affect, demonstrating the potential of this approach.

Evaluating the Effects of AI Directors for Quest Selection

Modern commercial games are designed for mass appeal, not for individual players, but there is a unique opportunity in video games to better fit the individual through adapting elements in games. In this paper, we focus on AI Directors, systems which can dynamically modify a game, that attempt to personalize the player experience to a player's preference. AI Directors have in the past provided inconclusive results, so their effect on player experience is currently unknown. In this paper, we take three AI Directors and directly compare them in a human subject study to test their effectiveness on quest selection. Our results show that a non-random AI Director provides a better player experience than a random AI Director.

Thoracic Responses and Injuries of Male Post-Mortem Human Subjects in a Homogeneous Rear-Facing Seat During High-Speed Frontal Impact.

In recent post-mortem human subjects (PMHS) studies in a high-speed rear-facing frontal impact (HSRFFI), the PMHS sustained multiple rib fractures. The seatback structure and properties of the seats might contribute to these fractures. This study aimed to determine if a homogeneous rear-facing seat with foam-covered seatback would mitigate the risk of thoracic injury during an HSRFFI. Three male PMHS were subjected to the same previous HSRFFI pulse. The seating structure consisted of a homogeneous seatback composed of rigid plates with load cells and covered with both comfort and safety foam. The PMHS spine was instrumented with accelerometers and angular rate sensors. Two chestbands were attached at the level of the axilla and xiphoid, and strain gages and strain rosettes were attached to ribs. Whole-body kinematics were quantified using a motion capture system. PMHS1 and PMHS3 sustained 30 and 13 rib fractures, respectively, while PMHS2 did not sustain any fractures. Average maximum anterior-posterior (A-P) chest compressions ranged from 15.9 to 22.6%. Rib fractures occurred before and after the maximum A-P compression, so A-P chest compression alone did not correlate well with rib fracture outcomes. Thoracic inferior-superior (I-S) deformation relative to the T12 was 107.4mm for PMHS1, 27.6mm for PMHS2, and 85.1mm for PMHS3. The direction of the maximum principal strain indicated that ribs experienced shear caused by I-S chest deformation. These results will assist with the development of countermeasures to protect occupants in a rear-facing seating configuration, along with validation of human body models.

Anesthetic neurotoxicity in the developing brain: an update on theinsights and implications for fetal surgery.

This review describes an in-depth analysis of the neurotoxicity associated with the anesthetic agents used during fetal surgery, intending to highlight the importance of understanding the effects of general anesthetics on the developing brain, particularly in the context of open fetal surgery, where high doses are applied to facilitate surgical access and augment uterine relaxation. We examined evidence from preclinical studies in rodents and primates, along with studies in human subjects, with the results collectively suggesting that general anesthetics can disrupt brain development and lead to long-lasting neurological deficits. Our review underscores the clinical implications of these findings, indicating an association between extensive anesthetic exposure in early life and subsequent cognitive deficits. The current standard of anesthetic care for fetal surgical procedures was scrutinized, and recommendations have been proposed to mitigate the risk of anesthetic neurotoxicity. These recommendations emphasize the need for careful selection of anesthetic techniques to minimize fetal exposure to potentially harmful agents. In conclusion, while the benefits of fetal surgery in addressing immediate risks often outweigh the potential neurotoxic effects of anesthesia, the long-term developmental impacts nevertheless warrant consideration. Our analysis suggests that the use of general anesthetics in fetal surgery, especially at high doses, poses a significant risk of developmental neurotoxicity. As such, it is imperative to explore safer alternatives, such as employing different methods of uterine relaxation and minimizing the use of general anesthetics, to achieve the necessary surgical conditions. Further research, particularly in clinical settings, is essential to fully understand the risks and benefits of anesthetic techniques in fetal surgery.

Comparative effects of ranolazine and trimetazidine on cardiac structure and exercise capacity in a healthy rat model: a new doping agent?

Abstract Background/Introduction Anti-anginal drugs that have been shown to improve myocardial energy use include ranolazine and trimetazidine [1]. An inquiry is warranted into their ability to impact cardiac functions and exercise capacity. Purpose This study aims to evaluate the effects of ranolazine; and trimetazidine as a positive control group on cardiac structure and exercise capacity in a rodent model in comparison with the control group. Methods In a randomized, controlled trial, 24 Sprague-Dawley rats were divided into three groups: control, ranolazine, and trimetazidine. Rats were given daily doses of ranolazine (50 mg/kg/1 ml) [2], trimetazidine (10 mg/kg/1 ml) [3], or saline (control) via gastric gavage for 30 days. At the beginning of the trial, as well as on the 15th and 30th days, the rats were weighed, placed on rotarod, and assessed using transthoracic echocardiography (Figure 1). The rats underwent 21 days of forced swimming testing. According to the guidelines for rat exercise testing [4], signs of exhaustion, lack of coordinated movements, and failure to surface for three seconds following submersion in the water were designated as grounds for terminating the test. Weight, rotarod durations, M-mode and Doppler measurements, and forced swimming test durations were recorded on the 0th, 15th, and 30th days. Results No discernible differences were found between the groups in the initial evaluations. By using echocardiography, the left ventricular masses expanded in all three, indicating the emergence of an athlete's heart. In comparison to the control group, the ranolazine and trimetazidine groups showed considerable increases in their ability to exercise. In particular, the swimming times of the trimetazidine group and the ranolazine group improved to a mean of 1889 seconds by the 21st session, 1700 seconds in the trimetazidine group, and 1548 seconds in the control group (Figure 2), respectively, indicating enhanced cardiac performance. Conclusion(s) Ranolazine exhibits significant potential to enhance exercise capacity and cardiac efficiency in rats, surpassing the effects observed with trimetazidine. Trimetazidine is already registered as a doping agent in WADA [5]. These findings highlight the potential use of ranolazine as a performance enhancing agent in healthy subjects for a malicious purpose of creating unfair advantages in professional sports. Further studies in human subjects are needed.Figure 1Figure 2

An Exploratory Study of Contextual Control Modes in Teamwork.

This study investigated the relationship between human team member contextual control and team performance under time constraints. Contextual control modes, which describe different strategies for action selection in dynamic environments, characterize how humans maintain performance under variable demands. Control modes have not yet been studied in teamwork settings. Modeling of the cross-level interaction between team members' control modes and emerging team behaviors can improve understanding of effective teamwork in dynamic environments. A human-subjects study explored the relationship between individual contextual control and team performance. Questionnaires about contextual control were used to elicit individual control modes. Analysis compared team members' control modes and investigated how control modes changed under varying time pressures. Participant's control modes differed in their look ahead horizon, the extensiveness of prior action evaluation, and their prior experience. Many team members shifted control modes during trials, resulting in both convergence and divergence of paired control modes. No effects on communication rate were found due to changes in team members' control modes, but partially significant findings may suggest that the control mode divergence affects performance. Teams can operate in multiple control mode configurations that change dynamically according to context. Further research with an increased sample size is warranted to analyze how time constraints influence team members' control modes and overall teaming processes and whether divergence of team control mode is favorable under time pressures. Further study of contextual control in teams may help improve team design to better support teams in coping with time constraints in dynamic environments.

Akustische Basissignale für mobile Logistik-Roboter

Abstract Increasing economic requirements and changes in the labor market are driving the use of mobile robots in intralogistics. Human-robot interaction should therefore be made more intuitive. This article presents a human subject study on the usability of innovative acoustic signals for robots in nine interaction situations, augmented by interviews with domain experts. The central finding is the necessity of dividing signal types into vehicle-like motion signals and humanizing interaction signals.

Synthesis of K+ channel radioligand [18F]5-methyl-3-fluoro-4-aminopyridine and PET imaging in mice

[18F]3-fluoro-4-aminopyridine ([18F]3F4AP) is the first positron emission tomography (PET) radioligand that targets voltage-gated potassium (K+) channels in the brain for imaging demyelination. [18F]3F4AP exhibits high brain penetration, favorable kinetics for PET imaging, and high sensitivity to demyelinating lesions. However, recent studies in awake human subjects indicate lower metabolic stability than in anesthetized animals, resulting in reduced brain uptake. Therefore, there is a need for novel radioligands for K+ channels with suitable pharmacological properties and enhanced metabolic stability. Recent in vitro studies demonstrate that 5-methyl-3-fluoro-4-aminopyridine (5Me3F4AP) exhibits comparable binding affinity to K+ channels, pKa, logD, and membrane permeability as 3F4AP, and a slower enzymatic metabolic rate, suggesting its potential as a K+ channel PET tracer. In this study, we describe the radiochemical synthesis of [18F]5Me3F4AP using an isotope exchange method from the corresponding 3-fluoro-5-methyl-4-nitropyridine N-oxide, followed by a palladium on carbon mediated hydrogenation of the nitro and N-oxide groups. This method yielded [18F]5Me3F4AP with high purity and acceptable molar activity. PET/CT studies using naïve mice demonstrate that [18F]5Me3F4AP effectively crosses the blood–brain barrier and has comparable kinetics to [18F]3F4AP. These findings strongly suggest that [18F]5Me3F4AP is a promising candidate for neuroimaging applications and warrant further studies to investigate its sensitivity to lesions and in vivo metabolic stability.

“I Don’t See Myself Represented Here at All”: User Experiences of Stable Diffusion Outputs Containing Representational Harms across Gender Identities and Nationalities

Though research into text-to-image generators (T2Is) such as Stable Diffusion has demonstrated their amplification of societal biases and potentials to cause harm, such research has primarily relied on computational methods instead of seeking information from real users who experience harm, which is a significant knowledge gap. In this paper, we conduct the largest human subjects study of Stable Diffusion, with a combination of crowdsourced data from 133 crowdworkers and 14 semi-structured interviews across diverse countries and genders. Through a mixed-methods approach of intra-set cosine similarity hierarchies (i.e., comparing multiple Stable Diffusion outputs for the same prompt with each other to examine which result is `closest' to the prompt) and qualitative thematic analysis, we first demonstrate a large disconnect between user expectations for Stable Diffusion outputs with those generated, evidenced by a set of Stable Diffusion renditions of `a Person' providing images far away from such expectations. We then extend this finding of general dissatisfaction into highlighting representational harms caused by Stable Diffusion upon our subjects, especially those with traditionally marginalized identities, subjecting them to incorrect and often dehumanizing stereotypes about their identities. We provide recommendations for a harm-aware approach to (re)design future versions of Stable Diffusion and other T2Is.

Renal Profile of Herbal Medicine Users and Nonusers: An Exploratory Cross-sectional Study in a Family Medicine Clinic in Nigeria

Abstract Context: A major risk of herbal medicine is the potential for toxicity and serious side effects. Unlike orthodox medicine, herbs are usually consumed without prior safety assessment via clinical studies. This means that the clinical effects of herbs may be detected only through an assessment of the health parameters of consumers. Aim: The study aimed to evaluate participants’ renal profiles, comparing that of herb users with nonusers, thereby identifying any differences between the two groups. Settings and Design: It is a cross-sectional, analytic study among adult patients attending the general outpatient unit of Abubakar Tafawa Balewa University Teaching Hospital, Bauchi, Nigeria. Materials and Methods: The study assessed and compared estimated glomerular filtration rate, microalbuminuria, and proteinuria among patients who reported using herbs and those who did not report any use. Statistical Analysis: Data were analyzed using Epi Info 7.2. Results: Three hundred and forty-one participants were enrolled. The mean eGFR was 87.47 ± 25.44 ml/min/1.73 m2 for participants who used herbs and 84.76 ± 25.49 ml/min/1.73 m2 for those who never used herbs (P value 0.48). Among all participants, proteinuria ≥0.3 g/l was present in 29 (8.50%) and microalbuminuria ≥30 mg/l in 138 (40.47%). There was no statistically significant difference in the renal parameters of both groups. Conclusion: The study found no evidence of the harmful effect of the herbs reported on kidney function. This could be because that the study participants mainly reported using edible—and, therefore, presumably safe—herbs. Further studies in human subjects of the effect of herbal medicine on the kidney and other systems are suggested.

Gut Microbiota Dysbiosis in the Pathogenesis of Metabolic-dysfunction Associated Steatotic Liver Disease (MASLD)

: Metabolic-dysfunction-associated steatotic liver disease (MASLD), previously referred to as nonalcoholic fatty liver disease (NAFLD), affecting approximately 30% of the global population. Projections suggest that MASLD incidence may rise by up to 56% over the next decade. MASLD has become the fastest-growing cause of hepatocellular carcinoma (HCC) in the USA, France, UK, and other regions worldwide. The prevalence of MASLD and MASLD-related liver damage is expected to parallel the increasing rates of obesity and type 2 Diabetes Mellitus (T2DM) globally. The factors contributing to MASLD development and its progression to metabolic-dysfunction- associated steatohepatitis (MASH), fibrosis, cirrhosis, and HCC remain poorly understood. Evidence from cell-based, animal-based, and human-subject studies suggests that insulin resistance, endoplasmic reticulum stress, oxidative stress, impaired autophagy, genetics, epigenetics, reduced immune surveillance, increased gut inflammation, and gut dysbiosis are crucial events in MASLD pathogenesis. In recent years, dysregulation of gut microbiota has emerged as a potential mechanism implicated in MASLD and MASLD-related hepatocarcinogenesis. This review briefly outlines the mechanistic events significant for MASLD pathogenesis. Additionally, it offers insight into dysregulated gut microbiota and its correlation with MASLD and MASLD-related liver damage. Furthermore, it highlights pertinent questions for cell and microbiologists in the MASLD research field. It underscores the necessity for identifying factors leading to gut microbiome dysregulation in MASLD and MASH pathogenesis. Identifying these factors could aid in the development of novel strategies for managing MASLD and MASLD-related liver damage.

THE IMMUNOMODULATORY ROLE OF CYTOKINES IN THE PATHOGENESIS OF PERIODONTAL DISEASE

Background:Inflammatory periodontal diseases are one of the most acute problems of modern dentistry, which is associated with their widespread prevalence in the world. In the structure of periodontal diseases, periodontitis a leading place in the age group of 40-50 years. Many factors play a role in the etiology of periodontitis, the most important of which are the local microbiota and the host immune response. Cytokines play an extremely important role. Cytokines are key modulators of both homeostasis and inflammatory processes, acting in the first wave of responses against pathogens, stimuli at barrier sites and linking tissue cells to lymphocytes and additional cell populations. Objective:The aim of the study was to analyze modern literature on the role of cytokines in the etiology and pathogenesis of inflammatory periodontal diseases. Materials and methods:Data Extraction: A comprehensive electronic literature search was performed in the following databases:PubMed, Scopus,Web of Scienc, Google Scholar, EBSCO host from 2000 to 2024 terms: periodontitis, infection, inflammation, immunity, cytokines, interleukin. 124 articles were found and 50 full-text articles of high methodological quality were selected according to the review method used, the PRISMA. Inclusion criteria:included clinical trials, considered randomized controlled trials, cross-sectional studies, casecontrol studies, and cohort studies in human subjects that evaluated the current literature on the periodontitis, infection, inflammation, immunity, cytokines, interleukin written in English articles.There was no limitation on minimal quality, minimal sample size, or the number of patients. Exclusion criteria were:original primary studies, due to language limitations , abstracts, letters to the editor, book chapters, case reports, conference abstracts, duplicate publications, and in vitro and in vivo animal experimental studies. Result:Many factors of general and local origin are involved in the development and progression of inflammatory periodontal diseases. Microorganisms and their products cause activation of the host immune system, which results in the release of cytokines and other proinflammatory biomarkers that cause tissue damage. The inflammatory process in periodontal tissues progresses through various stages, beginning with the infiltration of immune cells into the gingival tissue. Immune cells secrete proinflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α),which further promote inflammation and tissue destruction. The interaction between bacterial biofilm and the immune response, which is mainly controlled by cytokines, determines the course of periodontal disease. Conclusion:The etiology and pathogenesis of periodontal disease is quite complex, diverse and not yet fully disclosed. Cytokines are control and modulate the immune response in periodontitis

Integrated Biomarker Response Emphasizing Neuronal Oxidative Stress and Genotoxicity Induced by Oxamyl in Sprague Dawley Rats: Ameliorative Effect of Ginseng as a Neuroprotective Agent.

Climate change has led to increased and varying pest infestation patterns, triggering a rise in pesticide usage and exposure. The effects of oxamyl, a widely used nematicide in Egypt, encompasses typical signs of carbamate intoxication; nevertheless, long-term effects of oxamyl exposure, particularly on the nervous system, require further elucidation. This study systematically investigated the mechanism and manifestations of repeated subacute exposure to sublethal doses of oxamyl in male SD rats. Data showed a dose-dependent genotoxic effect, manifested as increased bone marrow micronuclei and decreased brain expression of key genes involved in neurogenesis and neuronal development. Coincidently, brain histopathology showed dose-dependent neurodegeneration in various regions, associated with a significant increase in GFAP immunoreactivity, indicative of neuroinflammation. Biochemical examination revealed a typical pattern of cholinesterase inhibition by carbamates in serum and brain tissue, as well as increased oxidative stress markers in the brain such as SOD activity reduction, alongside an increase in NO and MDA. The ability of Ginseng at a 100 mg/Kg dose to ameliorate the effects of oxamyl exposure was investigated. Ginseng use, either as a protective or therapeutic regimen, attenuated the observed genotoxic, neuroinflammatory, and biochemical alterations. Our results indicate that repeated exposure to oxamyl triggers an integrative neurotoxic response, driven by genotoxicity, oxidative stress, and neuroinflammation, that could trigger an increase in neurological and cognitive disorders. These findings emphasize the urgent need for confirmatory translational studies in human subjects to assess these changes and inform policy decisions regarding safe levels of usage and appropriate agricultural and public health practices.

Development and evaluation of a lutein-fortified yoghurt: Stability assessment, sensory properties and human bioavailability study

Lutein is a carotenoid that humans obtain primarily from green-leafy vegetables. However, due to generally low consumption of these foods, this bioactive is not sufficiently consumed. Therefore, there is growing interest in developing lutein-fortified foods to provide an additional source of lutein supplementation. In this study, we developed a lutein-fortified yoghurt and conducted a 72-hour single-dose bioavailability study in human subjects. Lutein remained stable in the yoghurt over shelf life at 14.6 mg of lutein per 100 g of yoghurt. Sensory evaluation yielded results similar to a lutein-free yoghurt. In the bioavailability study, consuming 100 g of lutein-fortified yoghurt significantly increased the average serum concentration of lutein by 1946.86 ± 1514.72 h μg·L−1 in human subjects, following a typical pharmacokinetic curve of absorption and decline. These findings confirm that our lutein-fortified yoghurt is suitable for commercial use and effectively enhances people’s serum lutein levels.

Low Pressure Heliox-based Rebreather System to Reduce Work of Breathing and Conserve Gas.

Background: To test the ability of a low-pressure, low-flow, Heliox-based rebreathing system to reduce work of breathing and conserve gas while preserving CO2 concentration, temperature, and humidity at physiological levels in a bench study.Methods: We performed a bench study of a novel low-pressure, low-flow, noninvasive Heliox rebreathing system with CO2 scrubber that was connected to an artificial lung simulator with careful monitoring of flow, pressure, work of breathing, oxygen (O2), carbon-dioxide (CO2), temperature, and humidity levels. Multiple runs of breathing were performed while manipulating levels of resistance (5 - 30 cm H2O/L/sec), gas mixtures (room air, 79% Helium 21% O2, and 70% Helium and 30% O2), and leak levels (ultra-low, low, and high).Results: We found significant reductions in work of breathing (up to 64%) while conserving gas with estimates of up to 54-fold reduction in medical gas wastage (P<0.001). Specifically, at resistances of 5, 10, 20, and 30 cm H2O/L/sec we demonstrated 64%, 57%, 36%, and 7% reduction in work of breathing (P<0.0001). Gas wastage was reduced by 10- to 54-fold while the end-tidal CO2 concentration, humidity, and temperature were maintained by the device at physiological levels.Conclusions: In a bench-test, a low-pressure, low-flow, noninvasive Heliox rebreathing system with CO2 scrubber reduced work of breathing and conserved gas while preserving CO2 concentration, temperature, and humidity at physiological levels. Future studies in human subjects need to be performed to determine whether reduction of work of breathing and gas conservation can be achieved.

Analysis of Circadian Clock Gene Expression in Human Skin Explants

Many aspects of skin biochemistry and physiology are known to vary over the course of the 24-hour day. Traditional approaches to study circadian rhythms in the skin have employed rodents or human subjects, which limit the experimental variables that can be studied. Although explants derived from discarded surgical skin are a commonly used model in the skin biology field, circadian rhythms have yet to be examined exvivo. In this study, using human panniculectomy skin, we used RT-qPCR to monitor the epidermal expression of 4 core circadian clock genes over the course of 1 day exvivo. Although significant interindividual variability in overall gene expression profiles was observed, robust circadian oscillations were observed in many of the genes and individual explants. Comparison of our gene expression data with microarray data from 2 previous human-subject studies involving primarily young adult White males revealed both similarities and differences, including greater distribution in the time of day of peak expression in the skin explants. This increased variability appears to be due in part to the increased age and altered sex distribution of the donated skin. Nonetheless, our results indicate that skin explants offer an additional experimental system for studying circadian skin biology.

Preservatives for postmortem brain tissue in biomechanical testing: A pilot study.

Postmortem human subject (PMHS) studies are essential to brain injury research in motor vehicle safety. However, postmortem deterioration reduces the similarity between postmortem test results and invivo response in material testing of brain tissue and in biomechanical testing of the whole head. This pilot study explores the effect of potential preservatives on brain tissue breakdown to identify promising preservatives that warrant further investigation. To identify preservatives with potential to slow postmortem degradation, samples from an initial PMHS were refrigerated at 10°C to qualitatively compare tissue breakdown from 58 to 152 h postmortem after storage in candidate solutions. On brain tissue samples from a second PMHS, compressive stiffness was measured on six samples immediately after harvest for comparison to the stiffness of 23 samples that were stored at 10°C in candidate solutions for 24 h after harvest. The candidate solutions were artificial cerebrospinal fluid (ACSF) without preservatives; ACSF with a combination of antibiotics and antifungal agents; ACSF with added sodium bicarbonate; and ACSF with both the antibiotic/antifungal combination and sodium bicarbonate. Results were analyzed using multiple linear regression of specimen stiffness on harvest lobe and storage solution to investigate potential differences in tissue stiffness. Qualitative evaluation suggested that samples stored in a solution that contained both the antibiotic/antifungal combination and sodium bicarbonate exhibited less evidence of tissue breakdown than the samples stored without preservatives or with only one of those preservatives. In compression testing, samples tested immediately after harvest were significantly stiffer than samples tested after 24 h of storage at 10°C in ACSF (difference: -0.27 N/mm, 95% confidence interval (CI): -0.50, -0.05) or ACSF with antibiotics/antifungal agents (difference: -0.32 N/mm, 95% CI: -0.59, -0.04), controlling for harvest lobe. In contrast, the stiffness of samples tested after storage in either solution containing sodium bicarbonate was not significantly different from the stiffness of samples tested at harvest. There was no significant overall difference in the mean tissue stiffness between samples from the frontal and parietal lobes, controlling for storage solution. Given the importance of PMHS studies to brain injury research, any strategy that shows promise for helping to maintain invivo brain material properties has the potential to improve understanding of brain injury mechanisms and tolerance to head injury and warrants further investigation. These pilot study results suggest that sodium bicarbonate has the potential to reduce the deterioration of brain tissue in biomechanical testing. The results motivate further evaluation of sodium bicarbonate as a preservative for biomechanical testing using additional test subjects, more comprehensive material testing, and evaluation under a broader set of test conditions including in whole-head testing. The effect of antibiotics and antifungal agents on brain tissue stiffness was minimal but may have been limited by the cold storage conditions in this study. Further exploration of the potential for microbial agents to preserve tissue postmortem would benefit from evaluation of the effects of storage temperature.

Injection of luteinizing hormone or human chorionic gonadotropin increases calcium excretion and serum PTH in males

Animal and human studies have suggested that sex steroids have calciotropic actions, and it has been proposed that follicle-stimulating hormone (FSH) may exert direct effects on bone. Here, we demonstrate the expression of the receptor for Luteinizing hormone (LH) and human choriogonadotropin (hCG), LHCGR, in human kidney tissue, suggesting a potential influence on calcium homeostasis. To investigate the role of LHCGR agonist on calcium homeostasis in vivo, we conducted studies in male mice and human subjects. Male mice were treated with luteinizing hormone (LH), and human extrapolation was achieved by injecting 5000 IU hCG once to healthy men or men with hypergonadotropic or hypogonadotropic hypogonadism. In mice, LH treatment significantly increased urinary calcium excretion and induced a secondary increase in serum parathyroid hormone (PTH). Similarly, hCG treatment in healthy men led to a significant increase in urinary calcium excretion, serum PTH levels, and 1,25 (OH)2D3, while calcitonin, and albumin levels were reduced, possibly to avoid development of persistent hypocalcemia. Still, the rapid initial decline in ionized calcium coincided with a significant prolongation of the cardiac QTc-interval that normalized over time. The observed effects may be attributed to LH/hCG-receptor (LHCGR) activation, considering the presence of LHCGR expression in human kidney tissue, and the increase in sex steroids occurred several hours after the changes in calcium homeostasis. Our translational study shed light on the intricate relationship between gonadotropins, sex hormones and calcium, suggesting that LHCGR may be influencing calcium homeostasis directly or indirectly.