Protracted Exposure to a Sub-background Radiation Environment Negatively Impacts the Anhydrobiotic Recovery of Desiccated Yeast Sentinels.

ABSTRACT: Experiments that examine the impacts of subnatural background radiation exposure provide a unique approach to studying the biological effects of low-dose radiation. These experiments often need to be conducted in deep underground laboratories in order to filter surface-level cosmic radiation. This presents some logistical challenges in experimental design and necessitates a model organism with minimal maintenance. As such, desiccated yeast ( Saccharomyces cerevisiae ) is an ideal model system for these investigations. This study aimed to determine the impact of prolonged sub-background radiation exposure in anhydrobiotic (desiccated) yeast at SNOLAB in Sudbury, Ontario, Canada. Two yeast strains were used: a normal wild type and an isogenic recombinational repair-deficient rad51 knockout strain ( rad51 Δ). Desiccated yeast samples were stored in the normal background surface control laboratory (68.0 nGy h -1 ) and in the sub-background environment within SNOLAB (10.1 nGy h -1 ) for up to 48 wk. Post-rehydration survival, growth rate, and metabolic activity were assessed at multiple time points. Survival in the sub-background environment was significantly reduced by a factor of 1.39 and 2.67 in the wild type and rad51 ∆ strains, respectively. Post-rehydration metabolic activity measured via alamarBlue reduction remained unchanged in the wild type strain but was 26% lower in the sub-background rad51 ∆ strain. These results demonstrate that removing natural background radiation negatively impacts the survival and metabolism of desiccated yeast, highlighting the potential importance of natural radiation exposure in maintaining homeostasis of living organisms.

Effects of prenatal dexamethasone exposure on adult C57BL/6J mouse metabolism and oxidative stress.

Prenatal glucocorticoid exposure has been shown to alter hypothalamic-pituitary-adrenal axis function resulting in altered fetal development that can persist through adulthood. Fetal exposure to excess dexamethasone, a synthetic glucocorticoid, has been shown to alter adult behaviour and metabolism. This study investigated the effects prenatal dexamethasone exposure had on adult offspring cardiac and liver metabolism and oxidative stress. Pregnant C57BL/6 mice received a dose of 0.4 mg/kg dexamethasone on gestational days 15-17. Once pups were approximately 7 months old, glucose uptake was determined using positron emission tomography and insulin resistance (IR) was determined by homeostatic model assessment (HOMA) IR calculation. Oxidative stress was assessed by measuring 4-hydroxynonenal protein adduct formation and total reactive oxygen species. Female dexamethasone group had significantly increased glucose uptake when insulin stimulated compared to vehicle-treated mice. HOMA IR revealed no evidence of IR in either male or female offspring. There was also no change in oxidative stress markers in either cardiac or liver tissues of male or female offspring. These data suggest that prenatal dexamethasone exposure in male mice does not alter oxidative stress or metabolism. However, prenatal dexamethasone exposure increased glucocorticoids, cardiac glucose uptake, and pAkt signaling in female heart tissues in adult mice, suggesting there are sex differences in prenatal dexamethasone exposure.

Pelvic arteriovenous malformation mimicking benign prostatic hyperplasia: A case report.

Pelvic arteriovenous malformation is a rare vascular abnormality, espescially in male patients, and is difficult to treat because of its nature supplied by multiple arterial feeders. We report a 70-year-old male patient admitted due to symptoms of benign prostatic hyperplasia. Ultrasound was performed initially, and no other abnormalities were found other than an enlarged prostate. CT scan later demonstrated a pelvic arteriovenous malformation adjacent to the prostate, with multiple arterial feeders from the right internal iliac artery. Angiography confirmed the diagnosis, and transaterial embolization was successfully done. The symptoms disappeared several days later, and the patient remained asymptompmatic during follow-up.

Digital health competencies for the next generation of physicians.

As health care continues to change and evolve in a digital society, there is an escalating need for physicians who are skilled and enabled to deliver care using digital health technologies, while remaining able to successfully broker the triadic relationship among patients, computers and themselves. The focus needs to remain firmly on how technology can be leveraged and used to support good medical practice and quality health care, particularly around resolution of longstanding challenges in health care delivery, including equitable access in rural and remote areas, closing the gap on health outcomes and experiences for First Nations peoples and better support in aged care and those living with chronic disease and disability. We propose a set of requisite digital health competencies and recommend that the acquisition and evaluation of these competencies become embedded in physician training curricula and continuing professional development programmes.

Absence of Depressive and Anxious Behavior with Genetic Dysregulation in Adult C57Bl/6J Mice after Prenatal Exposure to Ionizing Radiation.

The exposure of ionizing radiation during early gestation often leads to deleterious and even lethal effects; however, few extensive studies have been conducted on late gestational exposures. This research examined the behavior al effects of C57Bl/6J mouse offspring exposed to low dose ionizing gamma irradiation during the equivalent third trimester. Pregnant dams were randomly assigned to sham or exposed groups to either low dose or sublethal dose radiation (50, 300, or 1000 mGy) at gestational day 15. Adult offspring underwent a behavioral and genetic analysis after being raised under normal murine housing conditions. Our results indicate very little change in the behavioral tasks measuring general anxiety, social anxiety, and stress-management in animals exposed prenatally across the low dose radiation conditions. Quantitative real-time polymerase chain reactions were conducted on the cerebral cortex, hippocampus, and cerebellum of each animal; results indicate some dysregulation in markers of DNA damage, synaptic activity, reactive oxygen species (ROS) regulation, and methylation pathways in the offspring. Together, our results provide evidence in the C57Bl/6J strain, that exposure to sublethal dose radiation (<1000 mGy) during the last period of gestation leads to no observable changes in behaviour when assessed as adults, although some changes in gene expression were observed for specific brain regions. These results indicate that the level of oxidative stress occurring during late gestation for this mouse strain is not sufficient for a change in the assessed behavioral phenotype, but results in some modest dysregulation of the genetic profile of the brain.

All-inside arthroscopic anterior cruciate ligament reconstruction with internal brace Ligament Augmentation using semitendinosus tendon autograft: A case series.

Introduction and importance: Anterior Cruciate Ligament (ACL) reconstruction surgery has been proven to be closely related to the graft healing process, which can last up to 12 months after surgery. In recent years, through various biomechanical and clinical studies, Internal Brace Ligament Augmentation (IBLA) has been shown to protect the graft during these early postoperative stages and improve the outcome of ACL reconstruction. We present this case series of all-inside arthroscopic anterior cruciate ligament reconstruction with IBLA using semitendinosus tendon autografts, with the goal of evaluating postoperative clinical and patient-reported outcomes. Case presentation: A total of 37 patients who underwent all-inside arthroscopic anterior cruciate ligament reconstruction with IBLA using only semitendinosus tendon autografts, were evaluated, in terms of patient reported outcome and clinical assessment, during the 3, 6 and 12 months post-operative follow-up. Results: The mean Lysholm Knee score at the final follow-up was 94,03 +- 3,65 with a difference of 34,59 +- 5,52 to the baseline level. International Knee Documentation Committee (IKDC) classification rated 30 cases of grade A and 7 cases of grade B. In terms of clinical tests and knee's range of motion, all patients have returned to normal, and no cases of re-rupture or other severe complications were found. Clinical discussion: Early follow-up patient reported outcomes have provided good to great results for the 37 patients who underwent all-inside arthroscopic anterior cruciate ligament reconstruction with IBLA using semitendinosus tendon autografts and no cases of graft failure or other notable complication has been discovered. Clinical findings suggest improved knee's integrity and range of movement during the early stages, which may promote early rehabilitation, however future long-term comparative studies are needed. Conclusion: IBLA with all-inside ACL reconstructions using only semitendinosus autograft has provided good to great results however, future long-term comparative studies are needed.

Gene Dysregulation in the Adult Rat Paraventricular Nucleus and Amygdala by Prenatal Exposure to Dexamethasone.

Fetal programming is the concept that maternal stressors during critical periods of fetal development can alter offspring phenotypes postnatally. Excess glucocorticoids can interact with the fetus to effect genetic and epigenetic changes implicated in adverse developmental outcomes. The present study investigates how chronic exposure to the synthetic glucocorticoid dexamethasone during late gestation alters the expression of genes related to behavior in brain areas relevant to the regulation and function of the hypothalamic-pituitary-adrenal axis. Pregnant Wistar Kyoto rats received subcutaneous injections of dexamethasone (100 µg/kg) daily from gestational day 15-21 or vehicle only as sham controls. The amygdala and paraventricular nucleus (PVN) were micro-punched to extract mRNA for reverse transcription and quantitative polymerase chain reaction for the analysis of the expression of specific genes. In the PVN, the expression of the glucocorticoid receptor NR3C1 was downregulated in female rats in response to programming. The expression of CACNA1C encoding the Cav1.2 pore subunit of L-type voltage-gated calcium channels was downregulated in male and female rats prenatally exposed to dexamethasone. Collectively, the results suggest that prenatal exposure to elevated levels of glucocorticoids plays a role in the dysregulation of the hypothalamic-pituitary-adrenal axis and potentially learning and memory by altering the expression of specific genes within the amygdala and PVN.

Community-based Interventions to Prevent Dental Caries among Kindergarten Children in Vietnam: A 12-month Study of Field Trial.

AIM: To investigate the status of dental caries and assess the effectiveness of dental caries prevention interventions in children from 3 to 5-year-old in Hue City, Vietnam. MATERIALS AND METHODS: The subjects were 464 children and their direct caregivers at some kindergartens in Hue City from June 2020 to October 2021. The study included two consecutive phases: the first one was a cross-sectional study to identify the rate of dental caries and related factors in the studied kindergartens, and phase 2 was a controlled comparative interventional study for a period of 12 months. RESULTS: The mean of decayed, missing, filled, and DMFT index was 8.25, 0.09, 0.48, and 8.82, respectively, with no statistically significant difference in these figures between the living areas. The multivariable logistic regression model revealed some factors related to dental caries, including age, frequency of toothbrushing per day, parent-assisted toothbrushing, and eating and drinking sweets. Results showed the effectiveness of a community-based intervention for preventing dental caries, gingivitis, and plaque in the intervention group, compared to the control group. CONCLUSION: The rate of dental caries among Vietnamese children was remarkably high. A comprehensive intervention to prevent early childhood dental caries was effective and might be considered a necessary program in healthcare prophylaxis. CLINICAL SIGNIFICANCE: This intervention was consistent with the guidelines of WHO and based on evidences of related factors of dental caries identified in a previous cross-sectional study.

Chronic glucocorticoid exposure causes brown adipose tissue whitening, alters whole-body glucose metabolism and increases tissue uncoupling protein-1.

Adipose tissue (AT) has been found to exist in two predominant forms, white and brown. White adipose tissue (WAT) is the body's conventional storage organ, and brown adipose tissue (BAT) is responsible for non-shivering thermogenesis which allows mammals to produce heat and regulate body temperature. Studies examining BAT and its role in whole-body metabolism have found that active BAT utilizes glucose and circulating fatty acids and is associated with improved metabolic outcomes. While the beiging of WAT is a growing area of interest, the possibility of the BAT depot to "whiten" and store more triglycerides also has metabolic and health implications. Currently, there are limited studies that examine the effects of chronic stress and its ability to induce a white-like phenotype in the BAT depot. This research examined how chronic exposure to the murine stress hormone, corticosterone, for 4 weeks can affect the whitening process of BAT in C57BL/6 male mice. Separate treatments with mirabegron, a known ß3-adrenergic receptor agonist, were used to directly compare the effects of corticosterone with a beiging phenotype. Corticosterone-treated mice had significantly higher body weight (p ≤ 0.05) and BAT mass (p ≤ 0.05), increased adipocyte area (p ≤ 0.05), were insulin resistant (p ≤ 0.05), and significantly elevated expressions of uncoupling protein 1 (UCP-1) in BAT (p ≤ 0.05) while mitochondrial content remained unchanged. This whitened phenotype has not been previously associated with increased uncoupling proteins under chronic stress and may represent a compensatory mechanism being initiated under these conditions. These findings have implications for the study of BAT in response to chronic glucocorticoid exposure potentially leading to BAT dysfunction and negative impacts on whole-body glucose metabolism.

Effect of Prenatal Glucocorticoid Exposure on Circadian Rhythm Gene Expression in the Brains of Adult Rat Offspring.

Circadian clocks control many vital aspects of physiology from the sleep-wake cycle to metabolism. The circadian clock operates through transcriptional-translational feedback loops. The normal circadian signaling relies on a 'master clock', located in the suprachiasmatic nucleus (SCN), which synchronizes peripheral oscillators. Glucocorticoid receptor (GR) signaling has the ability to reset the phase of peripheral clocks. It has been shown that maternal exposure to glucocorticoids (GCs) can lead to modification of hypothalamic-pituitary-adrenal (HPA) function, impact stress-related behaviors, and result in a hypertensive state via GR activation. We previously demonstrated altered circadian rhythm signaling in the adrenal glands of offspring exposed to the synthetic GC, dexamethasone (Dex). Results from the current study show that prenatal exposure to Dex affects circadian rhythm gene expression in a brain region-specific and a sex-specific manner within molecular oscillators of the amygdala, hippocampus, paraventricular nucleus, and prefrontal cortex, as well as the main oscillator in the SCN. Results also show that spontaneously hypertensive rats (SHR) exhibited dysregulated circadian rhythm gene expression in these same brain regions compared with normotensive Wistar-Kyoto rats (WKY), although the pattern of dysregulation was markedly different from that seen in adult offspring prenatally exposed to GCs.

Within-Year Effects of Prescribed Fire on Bumble Bees (Hymenoptera: Apidae) and Floral Resources.

Despite the importance of bumble bees (genus Bombus Latreille) for their services to natural and agricultural environments, we know little about the relationship between grassland management practices and bumble bee conservation. Prescribed fire is a common grassland maintenance tool, including in areas where endangered and threatened bumble bees are present. Thus, knowledge of the effects of prescribed fire on bumble bees is essential for designing management schemes that protect and bolster their populations. Using nonlethal surveys to record bumble bee species richness, abundance, and community composition, we evaluated the effects of spring controlled burns on summer bumble bee gynes and workers across five sites in southern Wisconsin. In addition, we explored the effects of fire on floral resources by measuring floral genus richness, abundance, ground cover, and proportion of transects containing blooming flowers in adjacent burned and unburned parcels. Prescribed fire had no measurable effects on bumble bee gyne or worker community composition, species richness, or abundance. However, consistent with previous studies prescribed fire increased floral genus richness and ground cover. The disconnect between bumble bee and floral responses to fire highlights some opportunities for improving our understanding of fire's effects on bumble bee diapause, nest site choice, and foraging.

Profile of aeroallergen sensitizations in allergic patients living in southern Vietnam.

Background: Climatic and geographical characteristics may alter the plant distribution and thereby the patterns of allergens. Objective: To evaluate the profile of allergen sensitization in patients in southern Vietnam and its association with allergic diseases. Methods: We collected data of 423 patients who visited the Unit of Allergy and Clinical Immunology, University Medical Center, Vietnam from 2014 to 2021, from their medical records. Patients underwent skin prick tests to the 12 most common aeroallergens. Clinical evaluation and diagnosis of allergic diseases was done in consert with their allergen sensitization status. Results: Mites and cockroach were the most prevalent sensitizing allergens, with the sensitization prevalences as followed: Dermatophagoides farinae (Df) (59.8%), Dermatophagoides pteronyssinus (Dp) (50.4%), Blomica tropicalis (Bt) (49.6%), storage mites mix (10.4%), and cockroach (10.2%). Sensitization to Df was more predominant in males than in females (66% vs 54.1%). Dp-sensitized patients were younger than non-sensitized patients (29.01 ± 13.60 vs. 32.17 ± 14.89) whereas storage mites-sensitized patients were older than the non-sensitized groups (36.25 ± 13.53 vs. 28.76 ± 13.39) (p < 0.05 for all). A considerable proportion of patients with urticaria, allergic rhinitis, and atopic dermatitis were sensitized to mites. Polysensitization to different species of house dust mites (Dp, Df) and storage mites (Bt) was prevalent among patients sensitized to any kind of mites. Conclusions: Among people living in southern Vietnam, HDM mites, and cockroach were the predominant allergens. Further studies on the factors regulating the association between allergen sensitization with allergic diseases and polysensitization are crucial.

A scalable metal-organic framework as a durable physisorbent for carbon dioxide capture.

Metal-organic frameworks (MOFs) as solid sorbents for carbon dioxide (CO2) capture face the challenge of merging efficient capture with economical regeneration in a durable, scalable material. Zinc-based Calgary Framework 20 (CALF-20) physisorbs CO2 with high capacity but is also selective over water. Competitive separations on structured CALF-20 show not just preferential CO2 physisorption below 40% relative humidity but also suppression of water sorption by CO2, which was corroborated by computational modeling. CALF-20 has a low enthalpic regeneration penalty and shows durability to steam (>450,000 cycles) and wet acid gases. It can be prepared in one step, formed as composite materials, and its synthesis can be scaled to multikilogram batches.

Untargeted metabolomics reveals sex-specific differences in lipid metabolism of adult rats exposed to dexamethasone in utero.

Prenatal stress through glucocorticoid (GC) exposure leads to an increased risk of developing diseases such as cardiovascular disease, metabolic syndrome and hypertension in adulthood. We have previously shown that administration of the synthetic glucocorticoid, dexamethasone (Dex), to pregnant Wistar-Kyoto dams produces offspring with elevated blood pressures and disrupted circadian rhythm signaling. Given the link between stress, circadian rhythms and metabolism, we performed an untargeted metabolomic screen on the livers of offspring to assess potential changes induced by prenatal Dex exposure. This metabolomic analysis highlighted 18 significantly dysregulated metabolites in females and 12 in males. Pathway analysis using MetaboAnalyst 4.0 highlighted key pathway-level metabolic differences: glycerophospholipid metabolism, purine metabolism and glutathione metabolism. Gene expression analysis revealed significant upregulation of several lipid metabolism genes in females while males showed no dysregulation. Triglyceride concentrations were also found to be significantly elevated in female offspring exposed to Dex in utero, which may contribute to lipid metabolism activation. This study is the first to conduct an untargeted metabolic profile of liver from GC exposed offspring. Corroborating metabolic, gene expression and lipid profiling results demonstrates significant sex-specific lipid metabolic differences underlying the programming of hepatic metabolism.

DOSIMETRIC CHARACTERISATION OF A SUB-NATURAL BACKGROUND RADIATION ENVIRONMENT FOR RADIOBIOLOGY INVESTIGATIONS.

Living systems have evolved in the presence of naturally occurring ionising radiation. REPAIR is a research project investigating the biological effects of sub-natural background radiation exposure in SNOLAB, a deep-underground laboratory. Biological systems are being cultured within a sub-background environment as well as two control locations (underground and surface). A comprehensive dosimetric analysis was performed. GEANT4 simulation was used to characterise the contribution from gamma, muons and neutrons. Additionally, dose rates from radon, 40K and 14C were calculated based on measured activity concentrations. The total absorbed dose rate in the sub-background environment was 27 times lower than the surface control, at 2.48 ± 0.20 nGy hr-1, including a >400-fold reduction in the high linear energy transfer components. This modelling quantitatively confirms that the environment within SNOLAB provides a substantially reduced background radiation dose rate, thereby setting the stage for future sub-background biological studies using a variety of model organisms.

Lasting Effects of Low to Non-Lethal Radiation Exposure during Late Gestation on Offspring's Cardiac Metabolism and Oxidative Stress.

Ionizing radiation (IR) is known to cause fetal programming, but the physiological effects of low-dose IR are not fully understood. This study examined the effect of low (50 mGy) to non-lethal (300 and 1000 mGy) radiation exposure during late gestation on cardiac metabolism and oxidative stress in adult offspring. Pregnant C57BL/6J mice were exposed to 50, 300, or 1000 mGy of gamma radiation or Sham irradiation on gestational day 15. Sixteen weeks after birth, 18F-Fluorodeoxyglucose (FDG) uptake was examined in the offspring using Positron Emission Tomography imaging. Western blot was used to determine changes in oxidative stress, antioxidants, and insulin signaling related proteins. Male and female offspring from irradiated dams had lower body weights when compared to the Sham. 1000 mGy female offspring demonstrated a significant increase in 18F-FDG uptake, glycogen content, and oxidative stress. 300 and 1000 mGy female mice exhibited increased superoxide dismutase activity, decreased glutathione peroxidase activity, and decreased reduced/oxidized glutathione ratio. We conclude that non-lethal radiation during late gestation can alter glucose uptake and increase oxidative stress in female offspring. These data provide evidence that low doses of IR during the third trimester are not harmful but higher, non-lethal doses can alter cardiac metabolism later in life and sex may have a role in fetal programming.

Oxidative Stress Mediates the Fetal Programming of Hypertension by Glucocorticoids.

The field of cardiovascular fetal programming has emphasized the importance of the uterine environment on postnatal cardiovascular health. Studies have linked increased fetal glucocorticoid exposure, either from exogenous sources (such as dexamethasone (Dex) injections), or from maternal stress, to the development of adult cardiovascular pathologies. Although the mechanisms are not fully understood, alterations in gene expression driven by altered oxidative stress and epigenetic pathways are implicated in glucocorticoid-mediated cardiovascular programming. Antioxidants, such as the naturally occurring polyphenol epigallocatechin gallate (EGCG), or the superoxide dismutase (SOD) 4-hydroxy-TEMPO (TEMPOL), have shown promise in the prevention of cardiovascular dysfunction and programming. This study investigated maternal antioxidant administration with EGCG or TEMPOL and their ability to attenuate the fetal programming of hypertension via Dex injections in WKY rats. Results from this study indicate that, while Dex-programming increased blood pressure in male and female adult offspring, administration of EGCG or TEMPOL via maternal drinking water attenuated Dex-programmed increases in blood pressure, as well as changes in adrenal mRNA and protein levels of catecholamine biosynthetic enzymes phenylalanine hydroxylase (PAH), tyrosine hydroxylase (TH), dopamine beta hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT), in a sex-specific manner. Furthermore, programmed male offspring displayed reduced antioxidant glutathione peroxidase 1 (Gpx1) expression, increased superoxide dismutase 1 (SOD1) and catalase (CAT) expression, and increased pro-oxidant NADPH oxidase activator 1 (Noxa1) expression in the adrenal glands. In addition, prenatal Dex exposure alters expression of epigenetic regulators histone deacetylase (HDAC) 1, 5, 6, 7, 11, in male and HDAC7 in female offspring. These results suggest that glucocorticoids may mediate the fetal programming of hypertension via alteration of epigenetic machinery and oxidative stress pathways.

Mirabegron: The most promising adipose tissue beiging agent.

Accumulation of white adipose tissue (WAT) underlies the obesity epidemic, leading to current therapeutic techniques that are being investigated for their ability to activate/"beige" this tissue. Adipose tissue (AT) beiging has been reported through intermittent cold exposure (CE), exercise, and ß3-Adrenergic Receptor (ß3AR) agonists. But how AT beiging can help in the treatment of metabolic disorders like obesity and type 2 diabetes (T2D) remains largely unexplored. This review summarizes recent research on the use of ß3AR agonist, mirabegron (Myrbetriq®), in stimulating beiging in AT. Researchers have only recently been able to determine the optimal therapeutic dose of mirabegron for inducing beiging in subcutaneous/ inguinal WAT, where the benefits of AT activation are evident without the undesired cardiovascular side effects. To determine whether the effects that mirabegron elicits are metabolically beneficial, a comparison of the undisputed findings resulting from intermittent CE-induced beiging and the disputed findings from exercise-induced beiging was conducted. Given the recent in vivo animal and clinical studies, the understanding of how mirabegron can be metabolically beneficial for both lean and obese individuals is more clearly understood. These studies have demonstrated that circulating adipokines, glucose metabolism, and lipid droplet (LD) size are all positively affected by mirabegron administration. Recent studies have also demonstrated that mirabegron has similar outcomes to intermittent CE and displays more direct evidence for beiging than those produced with exercise. With these current findings, mirabegron is considered the most promising and safest ß3AR agonist currently available that has the potential to be used in the therapeutic treatment of metabolic disorders, and future studies into its interaction with different conditions may prove to be useful as part of a treatment plan in combination with a healthy diet and exercise.

Late gestational exposure to dexamethasone and fetal programming of abnormal behavior in Wistar Kyoto rats.

INTRODUCTION: Fetal programming was characterized a few decades ago, explaining the correlation of physiological phenotypes of offspring exposed to early-life stress. High acute or chronic prenatal stress can overwhelm the enzymatic placental barrier, inducing transcriptional changes in the fetus that can result in different adverse behavioral and physiological phenotypes. The current study investigates the impact of exposure to the synthetic glucocorticoid, dexamethasone, during late gestation on behavioral outcomes. METHODS: Pregnant Wistar Kyoto rats were given daily subcutaneous injections from gestational days 15-21 of either dexamethasone (0.9% NaCl, 4% EtOH, 100 µg kg-1  day-1 ) or were physically manipulated as naïve controls. Pups were raised normally until 17 weeks of age and underwent the Porsolt swim task and elevated plus maze for depressive and anxiety-like behaviors, respectively. Neural tissue was preserved for genetic analysis using quantitative real-time polymerase chain reaction. RESULTS: Statistical analyses show significant disruption of behavior and genetic profiles of offspring exposed to dexamethasone in-utero. Exposed animals spent more time immobile on the swim task and entered open arms of the elevated plus maze more often than their naïve counterparts. In the prefrontal cortex, there was a sex by treatment interaction on gene expression relevant to neural transmission in ryanodine receptor 2, as well as increased gene expression in SNAP25, COMT, and LSAMP in males prenatally exposed to dexamethasone compared with controls. Both dysregulated genes and behavior are linked to decreased anxiety and fear inhibition. CONCLUSION: Our results indicate adult offspring exposed to dexamethasone in-utero have a tendency toward passive stress-coping strategies and an inhibition of anxiety on behavioral tasks. Methyltransferase activity, synaptic activity, and cellular processes were disrupted in the prefrontal cortices of these animals. Specifically, genes involved in emotional response pathways were overexpressed, supporting the link between the behavioral and genetic profiles. Combined, we determine that dexamethasone offspring have adaptive predispositions when faced with novel situations, with increased immobility in the swim task and increased exploration on the elevated plus maze.

Unchanged cardiovascular and respiratory outcomes in healthy C57Bl/6 mice after in utero exposure to ionizing radiation.

BACKGROUND: Advancements in medical technologies that utilize ionizing radiation have led to improved diagnosis and patient outcomes, however, the effect of ionizing radiation on the patient is still debated. In the case of pregnancy, the potential effects are not only to the mother but also to the fetus. The aim of this study was to determine if exposure from ionizing radiation during pregnancy alters the development of the cardiovascular and respiratory system of the offspring. MATERIALS AND METHODS: Pregnant C57Bl/6 mice were whole-body irradiated at gestational day 15 with a 137Cs gamma radiation emitting source at 0 mGy (sham), 50 mGy, 300 mGy, or 1000 mGy. Post weaning weight and blood pressure measurements were taken weekly for both male and female pups until euthanasia at 16-17 weeks postnatal age. Immediately following, the trachea was cannulated, and the lungs and heart excised. The lung was then examined to assess respiratory physiological outcomes. RESULTS AND CONCLUSIONS: In utero exposures to 1000 mGy caused significant growth reduction compared to sham irradiated, which remained persistent for both male and female pups. Growth restriction was not observed for lower exposures. There was no significant change in any cardiovascular or respiratory outcomes measured. Overall, intrauterine exposures to ionizing radiation does not appear to significantly alter the development of the cardiovascular and respiratory system in C57Bl/6 pups up to 17 weeks postnatal age.