Rett syndrome (RTT), caused primarily by mutations in the X-linked MECP2 gene, is a neurodevelopmental disorder marked by systemic alterations, including mitochondrial dysfunction, chronic oxidative stress, and persistent subclinical inflammation. This OxInflammatory state suggests that disruption of redox-inflammatory regulatory pathways may contribute to disease pathophysiology. In this context, NF-κB and Nrf2 represent two important signaling regulators that operate in a coordinated crosstalk to balance inflammatory activation and antioxidant defense. In this study, we explored the functional status of NF-κB/Nrf2 crosstalk in primary dermal fibroblasts derived from RTT patients and healthy controls (CTR). Under basal conditions, RTT fibroblasts exhibited increased nuclear localization of NF-κB p65 and higher levels of acetylated NF-κB, indicating a constitutive inflammatory condition. In contrast, Nrf2 activation was not proportionally enhanced, suggesting an imbalance between inflammatory and antioxidant signaling. Following LPS stimulation, CTR fibroblasts displayed the expected coordinated activation of NF-κB and Nrf2 pathways, along with induction of downstream target genes. RTT fibroblasts, however, failed to activate either pathway and showed blunted transcriptional responses. These findings support the presence of a dysregulated signaling axis consistent with a chronic OxInflammatory state. Analysis of regulatory mechanisms revealed increased basal CBP/p300 levels in RTT cells without a compensatory increase in SIRT1, pointing toward altered acetylation dynamics that may favor persistent NF-κB activity. To mechanistically study the NF-κB/Nrf2 crosstalk, LPS-stimulated cells were treated with the Nrf2 activator sulforaphane (SFN), alone or combined with the NF-κB inhibitor BAY-117082. In RTT fibroblasts, these combined interventions significantly reduced pro-inflammatory cytokine expression and consistently enhanced HMOX1 transcription and HO-1 protein levels. Although nuclear localization changes were modest at the selected time point, downstream gene expression patterns indicated that coordinated modulation of inflammatory and antioxidant pathways can partially rebalance cellular responses. Taken together, our findings provide preliminary evidence that RTT exhibits a dysfunctional NF-κB/Nrf2 regulatory axis characterized by basal inflammatory activation and impaired antioxidant compensation. Modulation of NF-κB signaling, in combination with Nrf2 activation, may represent a promising strategy to counteract the persistent OxInflammatory milieu associated with RTT and warrants further investigation.

Fucoxanthin encapsulation in chitosan-carrageenan nanoparticles for improved stability and bioavailability.

B7-H3 (CD276) is an immune checkpoint co-signaling molecule expressed on immune and non-immune cells. It is best known for suppressing T-cell responses but can also promote inflammation depending on the microenvironment. In neuroinflammatory models such as experimental autoimmune encephalomyelitis, B7-H3 expression increases concomitantly with the inflammatory response, and its inhibition is associated with reduced disease progression. Although its role in ischemic stroke remains unclear, we hypothesized that cerebral ischemia/reperfusion (I/R) would upregulate B7-H3 expression in the ischemic brain and that increased B7-H3 expression would positively correlate with pro-inflammatory cytokine expression. Young and aged male and female rodents, including normotensive and spontaneously hypertensive rats to model comorbid hypertension, underwent transient middle cerebral artery occlusion (MCAO) followed by reperfusion. Brain tissue was collected on post-MCAO days 1, 3, 5, or 7. B7-H3 mRNA was analyzed by real-time PCR, whereas protein expression was assessed by Western blotting and immunohistochemistry at selected time points. B7-H3 expression was significantly upregulated in the ischemic brain across sexes, age groups, and species. The extent of B7-H3 degradation was influenced by species, sex, age, and time after cerebral I/R. Upregulation of B7-H3 was observed at both the mRNA and protein levels and was localized primarily to the somatosensory cortex and caudate putamen in the ipsilateral (ischemic) hemisphere, the main regions affected in this MCAO model. Elevated B7-H3 expression in the ischemic brain positively correlated with the pro-inflammatory mediator TNFα. In rats, the temporal profile of B7-H3 expression paralleled the early inflammatory phase associated with secondary tissue damage after ischemic stroke. These findings identify B7-H3 as an ischemia-induced immune checkpoint molecule in the brain that may modulate post-stroke immune responses and support further investigation into its beneficial versus detrimental roles in neuroinflammation and its potential as a therapeutic target following cerebral I/R.

Hip adduction and abduction strength recovery in senior male rugby union players during a full training and match week.

Background and Objectives: Enhanced Recovery After Surgery (ERAS) pathways are increasingly used in spine surgery, but uptake in adolescent idiopathic scoliosis (AIS) remains heterogeneous across institutions. Evidence in pediatric deformity surgery supports shorter recovery with protocolized care, yet real-world comparative data combining ERAS and the erector spinae plane block (ESPB) remain limited. This study aimed to compare early postoperative outcomes between a historical standard-care pathway and a structured ERAS+ESPB pathway in adolescents undergoing posterior spinal fusion for AIS. Materials and Methods: A single-center retrospective time-based comparative cohort study design included consecutive AIS patients (<18 years) treated between 1 January 2024 and 31 December 2025. The standard-care pathway was applied to patients operated on before 1 June 2025 (n = 34), whereas the ERAS+ESPB pathway was applied to those operated on from 1 June 2025 onward (n = 35), following formal institutional implementation. Outcomes included postoperative pain assessed using the visual analog scale under two functional conditions-at rest in the supine position and during standing/mobilization-at POD0, POD1, POD2, POD3, discharge, and 2-week follow-up; postoperative nausea at POD0-POD3; and length of stay (LOS). Between-group pain comparisons used Welch's t-test; nausea used Fisher's exact test; LOS used the Wilcoxon rank-sum test. Results: At POD0, supine pain was lower in ERAS+ESPB (1.50 ± 0.55) than in standard care (3.20 ± 1.50; p < 0.001). From POD1 onward, supine pain did not differ significantly between groups. Among assessable patients, standing pain was lower in ERAS+ESPB at POD2 (3.05 ± 1.53 vs. 4.50 ± 1.05; p = 0.020), POD3 (2.82 ± 1.62 vs. 4.17 ± 1.03; p = 0.006), and 2-week follow-up (1.45 ± 0.80 vs. 2.26 ± 0.93; p = 0.006). Nausea was lower in ERAS+ESPB at POD0 (11.4% vs. 35.3%; p = 0.024) and POD2 (8.6% vs. 32.4%; p = 0.018), with no significant differences at POD1 or POD3. LOS was shorter in ERAS+ESPB (5.41 ± 1.10 vs. 8.32 ± 2.06 nights; p < 0.001). Conclusions: In adolescents undergoing posterior spinal fusion for AIS, an ERAS-based perioperative pathway incorporating ESPB was associated with improved early postoperative recovery, particularly in terms of immediate postoperative pain, pain during mobilization, early postoperative nausea at selected time points, and length of hospital stay. Prospective multicenter studies are needed to confirm these findings and clarify the independent contribution of individual pathway components.

Exercise-induced muscle damage (EIMD) is known to impair neuromuscular performance, provoke inflammation, and delay recovery. Tart cherry (TC) juice, a polyphenol-rich nutritional product, has been proposed as a strategy to support recovery in athletes; however, findings across studies remain inconsistent. The aim was to conduct a systematic review combined with a meta-analysis and corroborate the certainty of evidence underpinning the effects of TC juice supplementation on physical, biochemical, and perceptual recovery markers following EIMD in trained athletes. A systematic review and meta-analysis were conducted following PRISMA 2020 guidelines. PubMed, ScienceDirect, Web of Science and SPORTDiscus were searched from inception to 25 December 2025. Nineteen trials were included. Our results revealed TC juice supplementation significantly improved MVC recovery in the main analysis across all time points (post: ES = 0.63; 24 h: ES = 1.12; 48 h: ES = 1.29; 72 h: ES = 2.14; 96 h: ES = 4.82), with substantial heterogeneity (I² 69-93%). CMJ showed no significant effects post-exercise or at 24h but improved at 48 h (ES = 1.41; I² = 72%). TC juice significantly reduced CRP post-exercise and up to 48 h (post: ES = -0.46; 24 h: ES = -0.73; 48 h: ES = -0.68), whereas no significant pooled effects were found for muscle soreness, CK, IL-6, TNF-α, ROM, or most subgroup time points. Subgroup analyses suggested model-specific responses (e.g., MVC improvements at 24-48 h in whole-body protocols and at 72 h in isolated protocols). Sensitivity analyses indicated that statistical significance at selected time points (MVC post and 72 h; CMJ 48 h; CRP 24-48 h) was influenced by individual studies. Certainty of evidence ranged from very low to moderate. TC juice supplementation may support recovery of selected functional and inflammatory markers following exercise-induced muscle damage in trained athletes; however, findings are heterogeneous and supported by low-to-moderate certainty of evidence, warranting cautious interpretation.

Biofilm formation on denture base materials may contribute to oral diseases such as denture stomatitis and therefore represents an important factor in prosthodontic treatment. This in vitro study investigated biofilm formation on dental prosthetic materials manufactured by additive, subtractive, and conventional techniques. Disc-shaped specimens were fabricated from 3D-printed Denture Base Resin (Formlabs), milled Lucitone Digital Fit (Dentsply Sirona), and conventionally processed cold-polymerized PALAPress (Kulzer). Biofilm formation by Streptococcus mutans and Streptococcus sanguinis was assessed separately over a 21-day incubation period using crystal violet staining and photometric determination of optical density at eight predefined time points. Surface characteristics before and after microbial colonization were qualitatively evaluated by scanning electron microscopy. For S. mutans, significant material-dependent differences were observed only at selected time points, while overall biofilm accumulation remained low. In contrast, S. sanguinis exhibited pronounced and repeated differences, with milled PMMA generally showing lower biofilm accumulation compared with additively manufactured and conventionally processed materials. Overall, S. sanguinis formed significantly more biofilm than S. mutans across all materials and time points. These findings indicate that both manufacturing technique and bacterial species influence biofilm formation on denture base materials.

Six-month Evaluation of Tooth Discoloration Induced by Bioceramic Sealers using Spectrophotometer and Digital Image Analysis: An In Vitro Study.

Background/Objectives: Mood disorders like depression, anxiety, and stress have increased steadily among adults, with growing interest in non-pharmaceutical treatments to improve symptomology. Epigallocatechin-3-gallate (EGCG) and curcumin are polyphenols with evidence to support their positive impacts on mood disorder symptomology and potential mood-associated biomarkers like brain-derived neurotrophic factor (BDNF). This study examined the effects of combined EGCG and curcumin supplementation on mood disturbance symptomology and serum brain-derived neurotrophic factor in adults. Methods: An 8-week randomized double-blinded placebo-controlled trial was conducted in adults (n = 64, 18-50 years old). Participants were randomized to a supplement group (n = 32; 350 mg EGCG and 1330 mg curcumin daily) or a matched placebo group (n = 32). Mood disturbance (DASS-21, GAD-7), sleep disturbance (GSAQ), and physical activity (IPAQ) were assessed at baseline, Week 4, and Week 8. Anthropometric measures, 24 h diet recalls, and fasted blood samples for serum BDNF were collected at baseline and Week 8. A multivariate ANOVA evaluated primary outcomes (DASS-21 composite score and BDNF), followed by repeated measures ANOVA for secondary outcomes (p < 0.05). Results: Significant improvements were observed across all participants for mood (DASS-21 composite and subscales, GAD-7, p < 0.001 for all), sleep (p < 0.001), and physical activity (p < 0.01), with no significant difference between supplement and placebo groups. Mean serum BDNF increased in both groups, but neither were statistically significant with no group-by-time interactions. Sugar intake (g/kg body weight) was positively correlated with mood symptoms at Week 8 in the supplement group. Baseline fruit and vegetable intake was associated with mood symptom severity at select time points; however, dietary changes during the intervention were not significantly related to changes in mood outcomes. Conclusions: Combined EGCG and curcumin supplementation did not show additional benefits beyond placebo for mood disturbance or serum BDNF over eight weeks. Observed improvements across both groups suggest that behavioral or lifestyle factors may play a larger role in short-term mood improvements than supplementation alone.

Spontaneous atlantoaxial facet joint autofusion after posterior C1-2 fusion.

Refractory chronic pain conditions remain challenging to manage, and intravenous infusions of ketamine, lidocaine, or their combination have emerged as potential therapeutic options. To evaluate the analgesic effectiveness and safety of intravenous lidocaine, ketamine, and their combination in patients with refractory chronic pain. We conducted a retrospective analytic study of patients treated between January 2020 and November 2024 at an outpatient pain clinic. Eligible patients had persistent severe pain (numerical rating scale [NRS] > 6/10) despite ≥ 3 months of multimodal pain management and received intravenous lidocaine, ketamine, or combination infusions. The primary outcome was immediate pain reduction post-infusion. Secondary outcomes included pain relief at 1 and 3 months, quality of life assessed by EQ-5D-5L, and associations between clinical characteristics and treatment response. A total of 120 patients were included. All three groups demonstrated significant reductions in NRS scores from baseline after the first infusion, with mean differences of 3.09 (95% CI 2.56-3.62) for lidocaine, 2.30 (95% CI 1.48-3.13) for ketamine, and 3.95 (95% CI 3.33-4.57) for combination therapy. Analgesic effects persisted at 1- and 3-month follow-up. Mild, self-limiting adverse effects occurred in 7.5% of patients. The combination group showed superior pain reduction at selected time points and greater improvements in quality of life at 3 months. Intravenous lidocaine, ketamine, and combination infusions provide immediate and sustained pain relief in refractory chronic pain. Combination therapy may offer additional benefit beyond monotherapy, supporting its consideration in clinical practice.

Type-2 diabetes mellitus (DM) increases tuberculosis (TB) risk and can worsen treatment outcomes. Both diseases and their treatments induce significant metabolic and biochemical perturbations that influence disease progression and management. This study longitudinally evaluated clinical, metabolic, and serum biochemical changes in patients with pulmonary TB with and without DM before and during anti-TB therapy. Ninety-five adult patients newly diagnosed with pulmonary TB in Ghana were stratified into TB-Only (n = 49; HbA1c < 6.5%) and TB-DM (n = 46; HbA1c ≥ 6.5%) groups, including treated (TB-DMt) and untreated (TB-DMnt) diabetes subgroups. Serum samples collected at baseline (t0), day 28 (t28), and day 56 (t56) were analyzed for electrolytes, renal function, liver enzymes, and lipid profiles using validated clinical chemistry analyzer. TB-DM cohorts exhibited significantly lower chloride levels at all time points relative to the TB-Only cohort (e.g., 98 vs. 100 mmol/L at t0, p < 0.001). Hyponatremia (serum sodium < 136 mmol/L) was prevalent during the intensive anti-TB treatment phase, affecting 53.1% of TB-Only patients, 61.1% of TB-DMt patients, and 70.0% of TB-DMnt patients. Liver function tests revealed elevated bilirubin, gamma-glutamyl transferase (g-GT), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) levels, particularly in TB-DMnt patients, with normalization over time. Lipid profiles showed a pro-atherogenic pattern with elevated triglycerides and total cholesterol (p < 0.05). High-density and low-density lipoproteins were increased at select time points. Positive correlations were noted among albumin, cholesterol fractions, and electrolytes. Primary microbiological treatment outcomes, including sputum conversion and completion rates, were similar regardless of diabetic status. The distinctive metabolic and biochemical derangements in TB-DM, especially untreated diabetes, highlight the importance of integrated clinical management. Elevated hepatic enzymes in TB-DMnt may delay metformin initiation, suggesting a need to optimize timing post hepatic recovery, while the prevalence of hyponatremia underscores the need for routine electrolyte monitoring in TB patients with diabetes. The dysregulated lipid profile highlights cardiovascular risk that warrants routine monitoring. Despite metabolic challenges, effective TB treatment outcomes are achievable with comprehensive care.

The effect of intradermal botulinum toxin type A injection on healing of porcine full-thickness wounds.

Tegoprazan is a potassium channel inhibitor with an anti-acid secretion effect. It is metabolized by CYP3A4, a cytochrome enzyme the occurrence of which in the Mexican population, differs from that in some other populations. Since the efficacy and safety studies on tegoprazan have been conducted in Koreans, it is of considerable clinical importance to establish whether differences exist in CYP3A4 metabolism between the two populations. To evaluate the oral pharmacokinetics of tegoprazan and to compare the pharmacokinetic data with those reported in the literature for Koreans. The investigation was carried out in a cohort of 20 healthy Mexican volunteers (11 women and 9 men), who were administered a dose of 50 mg after fasting for at least 10 hours. Blood samples were taken at selected time points over 24 hours, and tegoprazan plasma concentrations measured using high-performance liquid chromatography. Pharmacokinetic parameters were compared to those in Koreans reported in the literature. Tegoprazan is rapidly absorbed from the gastrointestinal tract reaching Cmax at ~ 1 hour post dose (tmax) and is removed from the circulation with an average half-life of ~ 4 hours. The pharmacokinetic parameters obtained were similar to those obtained in Koreans including elimination half-life, maximum tegoprazan concentrations, and oral bioavailability. Since no clinically relevant pharmacokinetic differences were observed in the pharmacokinetics of tegoprazan, a substrate for CYP3A4, between Mexicans and Koreans, it is concluded that the efficacy and safety data for tegoprazan obtained in Koreans will be valid in the Mexican population.

Children with acute lymphoblastic leukaemia (ALL) are at risk of metabolic and cardiovascular complications. We evaluated the development of overweight and obesity for 5 years after diagnosis in children and adolescents treated for ALL. The medical records of children diagnosed with ALL at one centre during 2000-2018 were assessed. Weight and height measurements were retrieved from medical records and were used to calculate age- and sex-adjusted International Obesity Task Force-Body Mass Index (ISO-BMI). ISO-BMI was determined at selected time points during treatment and up to 5 years after diagnosis, and the change in mean ISO-BMI was assessed. We studied 115 patients diagnosed with ALL, 54 (47%) of whom were male. Mean age at diagnosis was 6.6 ± 4.6 (range 0-17.99) years. ISO-BMI increased significantly during treatment (p < 0.0001) and remained elevated at 5 years after diagnosis (p < 0.0001). The number of overweight and obese patients increased from 17% and 4% at diagnosis to 26% and 16% at the five-year follow-up. Patients treated for ALL are at significant risk of weight gain and obesity, with the prevalence of overweight and obesity doubling from diagnosis to 5 years post-treatment. ISO-BMI remained persistently elevated across all treatment risk groups.

B7-H3 (CD276) is an immune checkpoint co-signaling molecule expressed on immune and non-immune cells. It is best known for suppressing T-cell responses but can also promote inflammation depending on the microenvironment. In neuroinflammatory models such as experimental autoimmune encephalomyelitis, B7H3 expression increases concomitantly with the inflammatory response, and its inhibition is associated with reduced disease progression. Although its role in ischemic stroke remains unclear, we hypothesized that cerebral ischemia/reperfusion (I/R) would upregulate B7-H3 expression in the ischemic brain and that increased B7-H3 expression would positively correlate with pro-inflammatory cytokine expression. Young and aged male and female rodents, including normotensive and spontaneously hypertensive rats to model comorbid hypertension, underwent transient middle cerebral artery occlusion (MCAO) followed by reperfusion. Brain tissue was collected on post-ischemic days 1, 3, 5, or 7. B7-H3 mRNA was analyzed by real-time PCR, whereas protein expression was assessed by Western blotting and immunohistochemistry at selected time points. B7-H3 expression was significantly upregulated in the ischemic brain across sexes, age groups, and species. The extent of B7-H3 degradation in the ischemic brain was influenced by species, sex, age, and time after cerebral I/R. Upregulation of B7-H3 was observed at both the mRNA and protein levels, and increased expression was localized primarily to the somatosensory cortex and caudate putamen in the ipsilateral hemisphere, the main regions affected in this MCAO model. Elevated B7-H3 expression in the ischemic brain positively correlated with the pro-inflammatory mediator TNFα. The temporal profile of B7-H3 expression observed in rats paralleled the early inflammatory phase associated with secondary tissue damage following ischemic stroke. These findings identify B7-H3 as an ischemia-induced immune checkpoint molecule in the brain that may modulate post-stroke immune responses and support further investigation into its beneficial versus detrimental roles in neuroinflammation, as well as its potential as a therapeutic target following cerebral I/R.

ABSTRACTBackgroundNon‐steroidal anti‐inflammatory drug‐exacerbated respiratory disease (N‐ERD) is characterised by the clinical triad of hypersensitivity to NSAIDs, nasal polyposis, and asthma. The cells and mediators causing acute symptoms when driving the hypersensitivity reaction to acetylsalicylic acid (ASA) ingestion, remain poorly defined.ObjectiveTo investigate the dynamics of nasal mediators during ASA provocation in N‐ERD patients before and 24 weeks after therapy with the IL‐4 receptor alpha‐blocking antibody dupilumab (EudraCT (2019‐004889‐18) and ClinicalTrials.gov (NCT04442256)).MethodsNasal mucosal lining fluids of patients with N‐ERD, chronic rhinosinusitis patients with nasal polyp (CRSwNP) and healthy disease controls were collected at selected time points up to 2 h after ASA provocation. Analysis of thirty‐three different inflammatory mediators as well as transcriptomic profiling was performed. In N‐ERD patients, provocation was repeated after 24 weeks of dupilumab therapy.ResultsSixty minutes after provocation with ASA, N‐ERD patients showed a significant increase in type 2 associated cytokines (i.e., TSLP, IL‐5 and eotaxin‐3) as compared to the other patient groups. This effect was diminished after 24 weeks of dupilumab therapy and was independent of the development of ASA tolerance. Transcriptomics revealed dampened upregulation of type 2 associated pathway genes (i.e., AREG) as well as enhanced downregulation of lipid (i.e., ALOX15) and peroxisome metabolisms (i.e., NOS2) at ASA provocation after dupilumab therapy.Conclusion and Clinical RelevanceTreatment with dupilumab leads to reduced nasal type 2 cytokine secretion and distinct changes in transcriptomic profile during ASA provocation, but changes in type 2 mediators show no association with tolerance development.Trial RegistrationEudraCT (2019‐004889‐18) and ClinicalTrials.gov (NCT04442256)

To compare the stone retropulsion of an artificial model of urinary stones in vitro using the new holmium:yttrium aluminium garnet (Ho:YAG) laser generator with a very low peak power pulse modulation mode (Quanta Magneto Technology™; Quanta System, Samarate, Italy) and thulium fibre laser (TFL). The following laser energy settings were used: 0.2 J-50 Hz, 0.4 J-25 Hz, 0.8 J-12 Hz, 1.5 J-6 Hz, and 2 J-5 Hz. A 5 × 5 × 5 mm cubic artificial stone was placed on two perpendicularly aligned metal rulers to create a V-shaped cross-sectional rail submerged in a tank filled with 0.9% saline solution, with the laser fibre in contact with the stone. The laser was activated for 5 s. Stone retropulsion was captured by a camera and assessed using video tracking software. Five repetitions were performed for each setting. Descriptive statistics investigated differences between the two lasers in stone retropulsion distance and speed at selected time points (0.35, 1, 3, and 5 s) and over the first second following laser activation. Comparable stone retropulsion distance and speed were observed between 'Magneto' and TFL according to tested high-energy settings. Magneto exhibited lower mean stone displacement at selected time points (all P < 0.02) and lower mean retropulsion speed over the first second following laser activation (all P < 0.01), when compared to TFL at low-energy settings (0.2 and 0.4 J). Although Ho:YAG lasers are generally associated with greater stone retropulsion compared to TFL, Magneto exhibited a retropulsion performance similar to TFL. Further research is needed to clarify the retropulsion dynamics observed with Magneto at low-energy settings.

Minimally invasive chevron osteotomy provides comparable outcomes to open surgery for hallux valgus: A systematic review and meta-analysis.

Disclosure: C. Ratner: Cecilia Ratner is emplyoed at Lundbeck A/S. V. Nielsen: Vibeke Nielsen is employed at Lundbeck A/S. M. Lubas: Michal Lubas is employed at Lundbeck A/S. M. Grupe Frost: Morten Grupe Frost is employed at Lundbeck A/S. A. Asuni: Ayodeji Asuni is employed at Lundbeck A/S.Elevated systemic glucocorticoid levels often result from exogenous glucocorticoid therapy, certain endocrine disorders such as Cushing’s syndrome and Cushing’s disease or in some psychiatric disorders with hypothalamic pituitary adrenal (HPA) axis overactivity including certain types of depression. In the present study, we aimed to assess how different treatment paradigms of chronic excess of glucocorticoids influence the dynamics of the HPA axis in a mouse model of exogenous corticosterone (CORT) treatment. CORT was administered to male C57Bl6/J mice for a duration of 21 days using three different treatment paradigms: Via the drinking water (80µg/ml), by subcutaneous pellet (7.5mg over 21 days) or by a combination of water (26.7µg/ml) and pellet (5mg over 21 days). Body weight was recorded throughout the study. Blood was sampled on day 7 and day 15 in the early light phase and just before lights out for CORT measurements. Mice were sacrificed on day 24 and pituitary glands were collected for gene expression analysis.To assess the reactivity of the HPA axis a separate cohort of mice treated with CORT pellets were subjected to acute restraint stress for 30 min on day 25 (4 days after end of CORT treatment). CORT treatment led to significantly lower body weight in some groups at select time points, but all groups showed trends toward lower body weight compared to control mice. All three types of CORT treatment resulted in increased plasma CORT levels in the early light phase on day 7 and day 15 compared to controls, while dark phase plasma CORT was similar between all groups. Overall, CORT levels were similar between the three treatment paradigms, but the water CORT group showed larger variability. CORT treatment reduced pituitary corticotropin releasing hormone receptor 1 (CRHR1) mRNA levels with no effect on proopiomelanocortin or glucocorticoid receptor mRNA levels. Treatment with CORT in the water reduced the vasopressin 1b receptor mRNA levels, which may be due to lower overall water intake. CORT treatment by subcutaneous pellets completely blocked the reactivity of the HPA axis to acute restraint stress. Overall, the three CORT treatment paradigms gave rise to similar results. The pellet treatment may be advantageous to obtain less variability in the model due to differences in water intake. CORT treatment gave rise to changes in the HPA axis including a significant downregulation of CRHR1, which may contribute to the lack of responsivity to acute stressorsPresentation: Sunday, July 13, 2025