Repeated Exposure Research Articles

Blood pressure response to exercise in endurance athletes with and without paroxysmal atrial fibrillation.

Abstract Background Atrial fibrillation (AF) is more prevalent among endurance-trained athletes when compared to non-athletes. The underlying pathophysiology and mechanisms for this phenomenon remain unknown but repeated exposure to an exaggerated blood pressure (BP) response during exercise may contribute to the development of AF in this population. Purpose We aimed to assess whether endurance athletes with AF have a higher maximal systolic BP (SBP) or a higher BP relative to exercise intensity compared to endurance athletes without AF. Methods Endurance athletes with paroxysmal AF (n=66, 96% male) from the ProAFHeart, NEXAF Detraining and Master@Heart studies were matched for age and sex to endurance athletes without AF (n=66, 96% male). Participants with a history of hypertension were excluded. All athletes underwent a maximal graded cardiopulmonary exercise test on a cycle ergometer to assess exercise BP using an automated auscultatory BP machine, maximal oxygen uptake (VO2peak) and peak workload. All athletes were in sinus rhythm at the time of testing and BP was measured pre-exercise seated on the bike and every 2 min throughout the test. Exercise BP measurements included the maximum exercise SBP (SBPmax) and the slopes of the relationships between SBP, diastolic BP (DBP) and workload (W) as determined from linear regression analysis (SBP/W-slope and DBP/W-slope, respectively). The resting SBP and DBP were measured in the supine position after 10min of rest. Independent T-test (parametric data) or the Mann-Whitney U-test (non-parametric data) assessed for the differences between the two groups. Results The 66 athletes with AF were of similar age and sex as the 66 athletes without AF, median age (55 [IQR 45, 61] vs 54 [IQR 44, 62] years, p=0.839), 4% female. There was no difference in (mean±SD) VO2peak (46 ±9 vs 49±10 mL/kg/min, p=0.114) and peak workload (365±67 vs 385±83 W, p=0.136), nor resting SBP (131±13 vs 128±13 mmHg, p=0.169) and resting DBP (76±9 vs 75±11 mmHg, p=0.465) between athletes with and without AF respectively (Table 1). Athletes with AF showed no significant difference to athletes without AF for exercise BP responses (Figure 1) including SBPmax (222±22 vs 219±28 mmHg, p=0.479), SBP/W-slope (0.22±0.07 vs 0.24±0.08 mmHg/W, p=0.310) and median DBP/W-slope (-0.01 [IQR -0.02, 0.01] vs -0.01 [IQR -0.03, 0.02] mmHg/W, p=0.703). Conclusion When comparing endurance athletes with and without paroxysmal AF, there were no differences in the maximal BP attained during exercise or in their BP response indexed to external workload (SBP/W-slope) suggesting that exercise-induced hypertension does not explain the athletic predisposition to AF.

Background predation risk induces anxiety-like behaviour and predator neophobia in zebrafish

Prey face a major challenge in balancing predator avoidance with other essential activities. In environments with high risk, prey may exhibit neophobia (fear of novelty) due to the increased likelihood of novel stimuli being dangerous. The zebrafish, Danio rerio, is an established model organism for many scientific studies. Although spatial and object neophobia in zebrafish have received previous attention, little is known about the role of background risk in inducing neophobia in zebrafish. Here, we present two experiments using zebrafish to explore whether background predation risk can induce anxiety-like behaviour in a novel environment and neophobic responses when exposed to a novel odour. Over five days, we repeatedly exposed zebrafish to either high background risk in the form of chemical alarm cues (i.e., injured conspecific cues that indicate a predator attack) or a low-risk water control stimulus. In Experiment 1, when tested in a novel tank, zebrafish exposed to high predation risk displayed anxiety-like responses (reduced activity and increased bottom time spent) compared to their low-risk counterparts. Moreover, high-risk individuals showed reduced intra-session habituation to the novel tank compared to low-risk individuals. In Experiment 2, high-risk individuals exhibited fear responses toward a novel odour, unlike low-risk individuals. These results reveal that short-term repeated exposures to high risk can induce anxiety-like behaviour and predator odour neophobia in zebrafish.

Effect of supplementation with lutein, zeaxanthin, and omega-3 fatty acids on macular pigment and visual function in young adults with long-term use of digital devices: study protocol for a randomized double-blind placebo-controlled study

BackgroundGrowing evidence emphasizes the importance of xanthophyll carotenoids and omega-3 fatty acids in eye health. However, the beneficial effects of such supplementation have not been thoroughly discussed among adults with high screen exposure. Current trial evidence on lutein bioavailability is contradictory, and the interactions of dietary intervention with host-related factors remain elusive. This study aims to investigate the comparative effectiveness of supplementation with macular xanthophylls and omega-3 fatty acids on macular pigment optical density (MPOD) and visual function, access the bioavailability of free lutein and lutein ester, and explore the complex interplay between genetic variations, intestinal microbiota, and the dietary intervention in Chinese adults with long-term exposure to digital devices.MethodsThe Lutein, Zeaxanthin, and Omega-3 (LZO) clinical trial is a 24-week multicenter, randomized, double-blind, placebo-controlled trial of 600 participants recruited from research centers, universities, and communities. Individuals are eligible to participate if they are aged over 18 years and use digital devices for over 8 h daily in the last 2 years, and will be randomized to six arms. A total of three visits will be scheduled at baseline, 12 and 24 weeks. The primary outcome is the change in MPOD over the 24-week intervention. The secondary outcomes are changes in visual function (visual acuity, best-corrected visual acuity, contrast and glare sensitivity, critical flicker fusion, reaction time, visuognosis persistence, symptoms and signs of dry eye, retinal thickness, and optical quality), and changes in serum lutein and zeaxanthin concentrations, and erythrocyte membrane omega-3 fatty acids. Genetic variations will be determined using genome-wide genotyping at baseline. 16S rRNA gene sequencing will be utilized to assess microbiome compositional changes before and after intervention.DiscussionThe trial is anticipated to establish early interventions to prevent photochemical ocular damage and delay the onset of vision impairment in young adults with long-term repeated exposure to screen-based electronic devices, and provide valuable insights for the development of precision nutrition strategies for maintaining eye health.Clinical trial registrationwww.clinicaltrials.in.th, Identifier, TCTR20220904002.

Repeated passive heat treatment increases muscle tissue capillarization, but does not affect postprandial muscle protein synthesis rates in healthy older adults.

Prolonged passive heat treatment (PHT) has been suggested to trigger skeletal muscle adaptations that may improve muscle maintenance in older individuals. To assess the effects of PHT on skeletal muscle tissue capillarization, perfusion capacity, protein synthesis rates, hypertrophy and leg strength, 14 older adults (9males, 5 females; 73 ± 6years) underwent 8weeks of PHT (infrared sauna: 3× per week, 45min at ∼60°C). Before and after PHT we collected muscle biopsies to assess skeletal muscle capillarization and fibre cross-sectional area (CSA). Basal and postprandial muscle tissue perfusion kinetics and protein synthesis rates were assessed using contrast-enhanced ultrasound and primed continuous l-[ring-13C6]phenylalanine infusions, respectively. One-repetition maximum (1RM) leg strength and vastus lateralis muscle CSA were assessed. Type I and type II muscle fibre capillarization strongly increased following PHT (capillary-to-fibre perimeter exchange index: +31 ± 18 and +33 ± 30%, respectively; P<0.001). No changes were observed in basal (0.24 ± 0.27 vs. 0.18 ± 0.11 AU; P=0.266) or postprandial (0.20 ± 0.12 vs. 0.18 ± 0.14 AU; P=0.717) microvascular blood flow following PHT. Basal (0.048 ± 0.014 vs. 0.051 ± 0.019%/h; P=0.630) and postprandial (0.041 ± 0.012 vs. 0.051 ± 0.024%/h; P=0.199) muscle protein synthesis rates did not change in response to prolonged PHT. Furthermore, no changes in vastus lateralis muscle CSA (15.3 ± 4.6 vs. 15.2 ± 4.6 cm2; P=0.768) or 1RM leg strength (46 ± 12 vs. 47 ± 12 kg; P=0.087) were observed over time. In conclusion, prolonged PHT increases muscle tissue capillarization but this does not improve muscle microvascular blood flow or increase muscle protein synthesis rates in healthy, older adults. Prolonged PHT does not induce skeletal muscle hypertrophy or increase leg strength in healthy, older adults. KEY POINTS: Repeated exposure to heat has been suggested to trigger skeletal muscle adaptive responses. We investigated the effect of 8weeks of whole-body passive heat treatment (PHT; infrared sauna: 3× per week for 45min at ∼60°C) on skeletal muscle tissue capillarization, perfusion capacity, basal, and postprandial muscle protein synthesis rates, muscle (fibre) hypertrophy, and leg strength in healthy, older adults. Prolonged PHT increases muscle tissue capillarization, but this does not improve muscle microvascular blood flow or increase muscle protein synthesis rates. Despite increases in muscle tissue capillarization, prolonged PHT does not suffice to induce skeletal muscle hypertrophy or increase leg strength in healthy, older adults.

6579 Neuroendocrine Signatures of Social-Defeated Stress Expressed by Adrenal Hormones in Mice

Abstract Disclosure: J. Noh: None. J. Choi: None. S. Myung: None. M. Kim: None. M. Choi: None. While psychological stress is one of the prevalent contributors to depression, the precise role of metabolic phenotypes in the development of depression remains elusive. Abnormality in hypothalamus-pituitary-adrenal (HPA) axis is a classical feature of depression. Here, an animal model of social defeat stress (SDS) was established with five-week-old C57BL/6J mice to repeated episodes of social defeat for a period of 10 days, facilitated by an aggressive CD-1 mouse. Liquid chromatography-mass spectrometry-based profiling of 29 adrenocortical steroids and 6 medullary amines was employed for serum samples collected at 3, 5, 7, and 10 days during the modeling from both control (n = 28) and SDS (n = 32) group. In response to initial stress, corticosterone (B) and its two precursors were significantly increased (p &amp;lt; 0.03 for all) during 3 days, while 18-hydroxyB was remarkably elevated (p &amp;lt; 0.003 for 3 days and p &amp;lt; 0.005) in SDS mice. In contrast, dopamine (p &amp;lt; 0.03) and metanephrine (p &amp;lt; 0.008) were significantly increased during 5 days in SDS mice, while remarkably higher levels of norepinephrine were also observed during 7 days (p &amp;lt; 0.01). The SDS mice showed the increased levels of normetanephrine for all days of repeated stress exposure (p &amp;lt; 0.002 for all, except 10 days of p &amp;lt; 0.02). In this study, the HPA regulated negative feedback in short period, whereas sympathetic nervous system was continuously stimulated during repeated stress exposure. The present study may provide insight into the neuroendocrine effects of social stress on allostatic overload. Presentation: 6/2/2024

Effective doses of scout projections in maxillofacial cone beam computed tomography.

To assess the effective and organ/tissue equivalent radiation doses of different scout projection protocols in four CBCT units. Optically stimulated luminescence dosimeters (OSLD) were placed in reference anatomical locations in the head and neck segments of an anthropomorphic phantom representing an average adult male. Ten repeated exposures were obtained from each of the twelve scout projections studied, acquired from four maxillofacial cone beam computed tomography (CBCT) units (Midmark EIOS, 3D Accuitomo F170, Veraviewepocs 3D R100, and Veraview X800). The effective and organ/tissue equivalent doses were calculated for each protocol. Effective doses ranged from 0.7 µSv (Accuitomo F170 60 × 60mm-anterior maxilla) to 6.9 µSv (Midmark 50 × 50mm-anterior maxilla). The highest organ/tissue equivalent doses were recorded for the oral mucosa and salivary glands; however, the thyroid was the highest contributor to the effective dose, followed by the salivary glands. Despite some variability among CBCT machines and protocols, the acquisition of scout projections is a low-dose procedure. The use of scout projections to ensure an adequate position of the region of interest within the field of view is highly desirable as they contribute minimally to overall CBCT patient dose.

Novel Mouse Model of Recurrent Sublethal Herpes Simplex Virus Infection Recapitulates Human Antibody Responses to Primary and Chronic Infection.

Background: Herpes simplex virus (HSV) vaccine development has been impeded by the absence of predictive preclinical models and defined correlates of immune protection. Prior candidates elicited neutralizing responses greater than natural infection but no antibody-dependent cellular cytotoxicity (ADCC) and failed to protect in clinical trials. Primary HSV infection also elicits only neutralizing responses, but ADCC and an expanded antigenic repertoire emerge over time. This evolution may contribute to the decreased frequency and severity of recurrences. To test this notion, we developed a recurrent HSV infection mouse model and evaluated changes in humoral immunity with repeated challenges. Methods: Mice were repeatedly infected intranasally with clinical isolates of HSV-1 or HSV-2 for four months. HSV binding IgG, neutralizing (with or without complement) and ADCC-mediating antibodies were quantified prior to each round of infection. Viral targets were assessed by western blotting. Pooled immune serum (750 μg IgG per mouse) was passively transferred into naïve wild-type or Hvem knockout mice 24 h prior to lethal skin challenge. Results: Repeated exposure to HSV-1 or HSV-2 induced an increase in total HSV-binding IgG but did not boost neutralizing titers. In contrast, ADCC-mediating responses increased significantly from the first to the fourth viral exposure (p < 0.01). The increase was associated with an expanded antigenic repertoire. Passive transfer of fourth round immune serum provided significant protection whereas first round serum failed to protect (p < 0.01). However, protection was lost when serum was transferred into Hvem knockout mice, which are impaired in mediating ADCC killing. Conclusion: This novel model recapitulates clinical responses, highlights the importance of ADCC in protecting against recurrent infection, and provides a strategy for evaluating therapeutic vaccines.

Bluetongue Virus in the Iberian Lynx (Lynx pardinus), 2010-2022.

Clinical infection and death caused by bluetongue virus infection has been reported in the Eurasian lynx. Bluetongue virus surveillance in the Iberian lynx revealed widespread and repeated exposure to serotypes 1 and 4 in wild and captive populations of this species. This exposure is possibly from a spillover event from sympatric ruminants.

An In-depth Analysis of the Adverse Effects of Ionizing Radiation Exposure on Cardiac Catheterization Staffs.

Diagnostic and interventional angiograms are instrumental in the multidisciplinary approach to CAD management, enabling accurate diagnosis and effective targeted treatments that significantly enhance patient care and cardiovascular outcomes. However, cath lab staff, including interventional cardiologists, is consistently exposed to ionizing radiation, which poses inherent health risks. Radiation exposure in the cath lab primarily results from the use of fluoroscopy and cineangiography during diagnostic and interventional procedures. Understanding these risks and implementing effective radiation protection measurements are imperative to ensure the well-being of healthcare professionals while delivering high-quality cardiac care. Prolonged and repeated exposure can lead to both deterministic and stochastic effects. Deterministic effects, such as skin erythema and tissue damage, are more likely to occur at high radiation doses. Interventional cardiologists and staff may experience these effects when safety measures are not rigorously followed. In fact, while ionizing radiation is essential in the practice of radiation cardiology ward, cath lab staff faces inherent risks from radiation exposure. Stochastic effects, on the other hand, are characterized by a probabilistic relationship between radiation exposure and the likelihood of harm. These effects include the increased risk of cancer, particularly for those with long-term exposure. Interventional cardiologists, due to their frequent presence in the cath lab, face a higher lifetime cumulative radiation dose, potentially elevating their cancer risk. Protective measures, including the use of lead aprons, thyroid shields, and radiation monitoring devices, play a crucial role in reducing radiation exposure for cath lab personnel. Adherence to strict dose optimization protocols, such as minimizing fluoroscopy time and maximizing distance from the radiation source, is also essential in mitigating these risks. Ongoing research and advancements in radiation safety technology are essential in further for minimizing the adverse effects of ionizing radiation in the cath lab.

Re‐Exposure to Culprit Medication Following Adverse Drug Event Diagnosis in Canadian Emergency Department Patients: A Cohort Study

ABSTRACTPurposeThe magnitude of repeat exposures to culprit medications after hospital discharge is not well studied. We combined prospective cohort data with administrative health data to understand the frequency of repeat exposures to culprit medications after discharge and the risk factors for their occurrence.MethodsThis was a retrospective analysis of three prospective cohorts of patients who presented to the hospital with an adverse drug event in British Columbia, from 2008 to 2015 (n = 849). We linked prospectively identified adverse drug events to administrative data to examine patterns of redispensing of culprit medications. We used Cox regression to assess risk factors for re‐exposure, and conducted subgroup analyses for essential vs. nonessential medications.ResultsAmong 849 diagnosed adverse drug events, 45.2% had subsequent culprit medication redispensing within a year of hospital discharge. The factors associated with re‐exposures included atrial fibrillation, adverse drug event type (e.g. adverse reaction), culprit medication type, and longer historical duration of medication use.ConclusionsRe‐exposures to culprit medications occurred in almost half of the adverse drug events diagnosed in emergency departments. Many of these were appropriate re‐exposures to essential medications for indications in which the risk of uncontrolled disease likely outweighed the risk of a repeat adverse event. More research is needed to understand re‐exposures to nonessential medications or medications with safer alternatives.

Cerium oxide nanoparticles (nanoceria) pretreatment attenuates cell death in the hippocampus and cognitive dysfunction due to repeated isoflurane anesthesia in newborn rats

General anesthetics exposure, particularly prolonged or repeated exposure, is a crucial cause of neurological injuries. Notably, isoflurane (ISO), used in pediatric anesthesia practice, is toxic to the developing brain. The relatively weak antioxidant system at early ages needs antioxidant support to protect the brain against anesthesia. Cerium oxide nanoparticles (CeO2-NPs, nanoceria) are nano-antioxidants and stand out due to their unique surface chemistry, high stability, and biocompatibility. Although CeO2-NPs have been shown to exhibit neuroprotective and cognitive function-facilitating effects, there are no reports on their protective effects against anesthesia-induced neurotoxicity and cognitive impairments. Herein, Wistar albino rat pups were exposed to ISO (1.5 %, 3-h) at postnatal day (P)7+P9+P11, and the protective properties of CeO2-NP pretreatment (0.5 mg/kg, intraperitoneal route) were investigated for the first time. The control group at P7+9+11 received 50 % O2 (3-h) instead of ISO. Exposure to nanoceria one-hour before ISO protected hippocampal neurons of the developing rat brain against apoptosis [determined by hematoxylin-eosin (HE) staining, immunohistochemistry (IHC) analysis with caspase-3, and immunoblotting with Bax/Bcl2, cleaved caspase-3 and PARP1] oxidative stress, and inflammation [determined by immunoblotting with 4-hydroxynonenal (4HNE), nuclear factor kappa-B (NF-κB), and tumor necrosis factor-alpha (TNF-α)]. CeO2-NP pretreatment also reduced ISO-induced learning (at P28–32) and memory (at P33) deficits evaluated by Morris Water Maze. However, memory deficits and thigmotactic behaviors were detected in the agent-control group; elimination of these harmful effects will be possible with dose studies, thus providing evidence supporting safer use. Overall, our findings support pretreatment with nanoceria application as a simple strategy that might be used for pediatric anesthesia practice to protect infants and children from ISO-induced cell death and learning and memory deficits.

Effects of repeated cryostimulation exposures on sleep and wellness in healthy young adults

The aim of this study was to evaluate the effects of daily whole-body cryostimulation (WBC) sessions during 5 consecutive days on wellness and sleep parameters in healthy young men and women. Twenty healthy subjects (9 women; 11 men) aged 23.1 ± 2.6 years old participated in this randomized protocol, with 5 consecutive days with (CRYO) or without WBC (CONT) exposure. Sleep was analyzed over the 5 nights in each condition. Sleep quality and quantity were assessed via actimetry, cerebral activity and questionnaires. Nocturnal heart rate variability (HRV) was also recorded and questionnaires were given to assess wellness and mood. Repeated WBC exposures had a beneficial impact on mood and anxiety. It also improved subjective sleep quality (scored from 3.6 ± 0.5 pre to 3.9 ± 0.3), especially in women. Also, repeated WBC sessions modulated sleep architecture by increasing slow wave sleep duration (+7.3 ± 16.8 min) during the nights without impacting other sleep parameters, nor nocturnal HRV. In conclusion, repeated WBC seems to be an effective strategy to improve slow wave sleep duration in healthy young subjects. The reported psychological improvements may better benefit women than men.

Solid Metal Chemical and Thermal Injury Management.

Solid metals may create a variety of injuries. White phosphorous (WP) is a metal that causes both caustic and thermal injuries. Because of its broad use in munitions and smoke screens during conflicts and wars, all military clinicians should be competent at WP injury identification and acute therapy, as well as long-term consequence recognition. English-language manuscripts addressing WP injuries were curated from PubMed and Medline from inception to January 31, 2024. Data regarding WP injury identification, management, and sequelae were abstracted to construct a Scale for the Assessment of Narrative Review Articles guideline-consistent narrative review. White phosphorous appears to be ubiquitous in military conflicts. White phosphorous creates a characteristic wound appearance accompanied by smoke, a garlic aroma, and spontaneous combustion on contact with air. Decontamination and burning prevention or cessation are key and may rely on aqueous irrigation and submersion or immersion in substances that prevent air contact. Topical cooling is a key aspect of preventing spontaneous ignition as well. Disposal of all contaminated clothing and gear is essential to prevent additional injury, especially to rescuers. Long-term sequelae relate to phosphorous absorption and may lead to death. Chronic or repeated exposure may induce jaw osteonecrosis. Tactical Combat Casualty Care recommendations do not currently address WP injury management. Education and management regarding WP acute injury and late sequelae is essential for acute battlefield and definitive facility care. Resource-replete and resource-limited settings may use related approaches for acute management and ignition prevention. Current burn wound management recommendations should incorporate specific WP management principles and actions for military clinicians at every level of skill and environment.

Development and validation of the UHPLC-MS/MS method for the quantitative determination of 25 PFAS in dried blood spots.

Per- and polyfluoroalkyl substances (PFAS) are anthropogenic fluorine-containing compounds largely used in industrial and consumer applications. They tend to bioaccumulate in the human body after intake from various sources in daily life. Following repeated exposure to PFAS, a broad range of adverse health outcomes has been reported. Consequently, monitoring PFAS levels in human blood is of paramount importance for public health policies. In contrast with traditional venipuncture, dried blood spots (DBS) constitute a reliable, cheap, and less invasive technique to allow microsampling by capillary blood collected on a specific device. This work aimed to develop and validate an innovative analytical method, combining quantitative DBS with UHPLC-MS/MS instrumentation to identify and quantify 25 PFAS. The extraction procedure was developed and optimized within the range 2-100ng/mL. Specifically, fortified blood was applied on Capitainer®B devices providing 10 μL of blood volume through a microfluidic channel. After 3h of drying, the extraction was performed by methanol under sonication, followed by centrifugation. Then, the extraction solvent was evaporated; the residue was reconstituted with the mobile phase solution. The validated method evidenced good sensitivity, with limits of detection ranging from 0.4ng/mL (PFODA, PFOS) to 1.0ng/mL (PFOA, 3,6-OPFHpA). The ± 20% acceptability criteria established for intra- and inter-day precision and accuracy were fulfilled for all analytes. High recovery-above 80%-was recorded, whereas significant matrix effect resulted in ion enhancement (> 50%) for 13 analytes. In conclusion, the proposed workflow proved to be reliable, fit for purpose, and easily adaptable in the laboratory routine.

Anxiety-like Characteristics, Forepaw Thermal Sensitivity Changes and Glial Alterations 1 Month After Repetitive Blast Traumatic Brain Injury in Male Rats

Background Many military service members are victims of repetitive blast traumatic brain injuries (rbTBI) and endure diverse altered psychological and behavioural conditions during their lifetime. Some of these conditions include anxiety, post-traumatic stress and pain. Thus, this study attempts to fill the knowledge gap on enduring behavioural and neuroinflammatory marker alterations 1 month after rbTBI. Purpose Although previous rbTBI animal studies have shown behavioural and histopathological changes either a few days (acute) or many months (chronic) after trauma, knowledge related to post-traumatic changes during the intermediate timeframe, i.e. a month after rbTBI is less clear or unavailable. Methods Sprague–Dawley rats (male; n = 12) were assigned to either rbTBI or sham conditions. Animals assigned to the rbTBI group were subjected to 1 blast exposure per day for three consecutive days, while animals in the sham group were exposed to identical experimental conditions sans blast exposure. All animals were tested for anxiety at baseline. 30 days post-injury, animals were tested again for anxiety and paw thermal sensitivity, followed by brain harvest for immunohistochemical analyses. Results Animals exposed to rbTBI showed signs of anxiety-like behaviour on parameters of elevated plus-maze and behavioural signs of pain indicated by reduced thermal withdrawal latency of the forepaw. Histologically, brain sections from animals exposed to rbTBI showed a significantly increased number of microglial/macrophage and astrocytic counts in the medial prefrontal cortex. Conclusion Data from this initial preclinical study support the prevalence of putative anxiety-like behaviour, enhancement in forepaw thermal sensitivity and increase in the number of glial cells even 1 month after rbTBI. These findings have potential implications in the treatment evaluation of blast-exposed military and civilian populations and emphasise the need for devising protective measures for people susceptible to single or repeated exposures. A greater further understanding of rbTBI-related chronic concurrent behavioural and neuropathological sequela is warranted.

A big bang theory of big brain trauma.

One of the biggest neurophysiological science news headlines of the 2024 summer reported a critical link between post-traumatic stress disorder (PTSD), suicide, and brain injury from blast events in members of the elite US fighting force, Navy SEALS. Researchers from the Department of Defense/Uniformed Services University Brain Tissue Repository (DOD/USU BTR) had discovered a border of neural damage between the layers of white and gray matter comprising the cortical folds of service members' brains. Described as a distinctive anatomical line of astroglial scarring along the shared junctions of gray and white cellular zones of the brain, this tissue injury was unlike that observed for concussive brain trauma. Rather, it was consistent with blast biophysics of mammalian tissues. In this new study, the damage appears to be correlated with long-term, repeated exposure to blast waves from nearby explosions or firing weapons. A cascade of progressive unexplained behaviors, cognitive decline, and severe depression in the trained fighters ensued. This analysis suggested that repetitive, impulsive pressure waves traveling through the service members' heads and brains with each blast had compromised their cognitive centers, setting a downward trajectory in their mental and physical health.

Increased Levels of Phosphorylated-P38α Induce WNT/β-Catenin and NGF/P75NTR/TrkA Pathways Disruption and SN56 Cell Death following Single and Repeated Chlorpyrifos Treatment.

Chlorpyrifos (CPF) biocide, exposure to which is mainly produced in the human population through diet, induces several neurotoxic effects. CPF single and repeated exposure induces memory and learning disorders, although the mechanisms that produce these outcomes are complex and not well understood. CPF treatment (single and repeated) of cholinergic septal SN56 cells induced an increase in phosphorylated-P38α levels that led to WNT/β-Catenin and NGF/P75NTR/TrkA pathways disruption and cell death. These results provide new knowledge on the mechanisms that mediate CPF basal forebrain cholinergic neuronal loss induced by CPF single and repeated exposure and can help unravel the way through which this compound produces cognitive decline and develop efficient treatments against these effects.

Antibacterial and oral tissue effectiveness of a mouthwash with a novel active system of amine + zinc lactate + fluoride.

Reflecting the need for an effective support for the daily oral hygiene routine of patients experiencing (symptoms of) gum inflammation, a new mouthwash has been developed containing an amine + zinc lactate + fluoride system. The in vitro efficacy of this product was assessed using traditional laboratory methods, as well as novel experimentation. This mouthwash has been evaluated in a series of laboratory tests including two short interval kill tests (SIKTs), a 12-h (longer term) biofilm regrowth assay, a plaque glycolysis assay, and an aerobic, repeated exposure biofilm model, as well as tests for soft tissue uptake and LPS neutralization. Several laboratory studies demonstrate that a mouthwash containing an amine + zinc lactate + fluoride system provides short-term and long-term antibacterial activity. While the immediate efficacy of this formula has been shown to be driven by the presence of the amine, zinc lactate provides a long-term antibacterial effect, as well as is able to inhibit bacterial metabolism. This research provides the basis for understanding the mode of action of this new mouthwash formulation and explains the previously observed clinical efficacy of this formula against plaque and gingivitis.

Fifteen day repeat air: liquid Interface air-only exposures can cause respiratory epithelium injury in MucilAir™ nasal respiratory epithelial cells that parallels chemically induced cytotoxicity

New Approach Methodologies (NAMs) are being widely used to reduce, refine, and replace, animal use in studying toxicology. For respiratory toxicology, this includes in silico and in vitro alternatives using air:liquid interface (ALI) exposures to replace traditional in vivo inhalation studies. In previous studies using 1,3-dichloropropene (1,3-DCP), a 5-day 4 h repeat exposures of MucilAir™ nasal cell culture models caused, dose-dependent cytotoxicity, depletion of GSH, changes in differential gene expression and histopathological transitions in cellular morphology from pseudostratified columnar epithelium to squamous epithelium. In this report we attempted to extend these studies using 15-day 1,3-DCP 4 h exposures to using MucilAir™ nasal cultures as outlined by an US EPA recent task order (US EPA 2023). For the 15-day repeat exposure, there were severe histopathologic changes in the MucilAir™ nasal mock-treatment (air-only) VITROCELL® chamber controls compared to incubator controls preventing any further analysis. The histopathological transitions in cellular morphology from pseudostratified columnar epithelium to squamous epithelium observed in the air only control in this study and previously with 1,3-DCP in MucilAir™ nasal cultures is also a hallmark of chemically induced cytotoxic responses in vivo in the respiratory tract. Histopathology assessments of 3D respiratory tract models used in ALI exposures can provide the linkage between in vitro to in vivo outcomes as part of the validation efforts of ALI use in regulatory toxicology. This report indicates that importance of histopathological assessments of incubator and mock-treatment (air-only) controls from each ALI exposure experiment along with exposed cell based model.

Hemin-Induced Transient Senescence Via DNA Damage Response: A Neuroprotective Mechanism Against Ferroptosis in Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) poses acute fatality and long-term neurological risks due to hemin and iron accumulation from hemoglobin breakdown. Our observation that hemin induces DNA double-strand breaks (DSBs), prompting a senescence-like phenotype in neurons, necessitating deeper exploration of cellular responses. Using experimental ICH models and human ICH patient tissue, we elucidate hemin-mediated DNA damage response (DDR) inducing transient senescence and delayed expression of heme oxygenase (HO-1). HO-1 co-localizes with senescence-associated β-Galactosidase (SA-β-Gal) in ICH patient tissues, emphasizing clinical relevance of inducible HO-1 expression in senescent cells. We reveal a reversible senescence state protective against acute cell death by hemin, while repeat exposure leads to long-lasting senescence. Inhibiting early senescence expression increases cell death, supporting the protective role of senescence against hemin toxicity. Hemin-induced senescence is attenuated by a pleiotropic carbon nanoparticle that is a catalytic mimic of superoxide dismutase, but this treatment increased lipid peroxidation, consistent with ferroptosis from hemin breakdown released iron. When coupled with iron chelator deferoxamine (DEF), the nanoparticle reduces hemin-induced senescence and upregulates factors protecting against ferroptosis. Our study suggests transient senescence induced by DDR as an early potential neuroprotective mechanism in ICH, but the risk or iron-related toxicity supports a multi-pronged therapeutic approach.