This study evaluated humpback whale (Megaptera novaeangliae) occurrence off the Pacific coast of Costa Rica from 2001 to 2023, focusing on two Distinct Population Segments (DPSs), the Central America DPS and the Southeast Pacific DPS, which migrate from feeding grounds in opposite hemispheres. Using long-term sightings and Bayesian time-series and habitat models, we quantified the influence of absolute dynamic topography, sea surface temperature, and chlorophyll-a on whale occurrence, and assessed whether environmental conditions increased the likelihood of convergence between the two DPSs. Extreme environmental conditions, including El Niño events and marine heatwaves, negatively affected whale counts, particularly for the Central America DPS, and a sustained decline occurred from 2007 to 2019 followed by recent recovery. Seasonal and interannual patterns indicated a potential temporal overlap of both DPSs between October and November, with anomalous warming in the Northern Hemisphere increasing the probability of overlap. These results demonstrate climate-driven shifts in migratory patterns and connectivity, underscoring the need for continuous monitoring and improved tracking of both DPSs to inform conservation planning, whale-watching management, and the protection of critical breeding habitats.
Costal cartilage is commonly used in nasal reconstruction due to its strength and biocompatibility; however, warping of carved struts remains a challenge. Although proteoglycans (PGs) are known to generate internal swelling pressures contributing to warping, the role of collagen fiber orientation in modulating these stresses and the spatial interplay between PGs and collagen across costal cartilage remains poorly understood. This study compared regional variations in collagen alignment and PG distribution from 2 anatomical sites: one that when transversely cut demonstrates no warping, and one that has higher tendency to warp. Human costal cartilage samples were collected from the sixth/seventh rib costal bridge (autograft) and long rib (allograft). Collagen fiber orientation was assessed using diffusion tensor imaging/tractography and polarized light microscopy. Matrix composition was evaluated via histology. Fractional anisotropy and mean diffusivity maps were used to correlate structural and compositional patterns. In the costal bridge and long rib cartilage, collagen fibers were predominantly aligned anterior-posterior in the mid and deep zones, with a tangential circumferential alignment near the surface. PG content was concentrated in the mid and deep zones and depleted superficially. These results suggest that cartilage warping arises from internal stress imbalances linked to regional variations in PGs and collagen. The elucidated microstructural geometry of struts sliced transversely from the costal bridge preserves matrix architecture and the circumferential tension band, preventing warping due to unresisted PG expansion. In contrast, disruption of the collagen fibers and unbalanced PG distribution in long cylindrical ribs leaves nonperfectly concentric carved struts, prone to deformation.
Coral reefs are vital ecosystems that support marine biodiversity and provide essential services to coastal economies. However, they are increasingly threatened by different contaminants, such as polycyclic aromatic hydrocarbons (PAHs), toxic compounds mainly derived from petroleum activities and the combustion of organic matter. This study evaluated the acute accumulation of these contaminants in the endemic Brazilian coral Mussismilia hispida, collected from the Marine Protected Area Costa dos Corais (MPACC) and experimentally exposed to three concentrations (50, 150, and 300 μg L-1) of the eight priority PAHs under controlled laboratory conditions. PAHs concentrations were analyzed in seawater, coral tissues, and skeletons using gas chromatography coupled with mass spectrometry (GC/MS). Concentrations of total PAHs ranged from 3.83 μg L-1 to 141.7 μg L-1, 96.2 μg g-1 to 329.1 μg g-1, 48.9 μg g-1 to 237.9 μg g-1 in seawater, tissues, and skeleton, respectively. The results revealed a clear pattern of dose-dependent accumulation, with coral tissues exhibiting higher PAHs retention than skeletons. In seawater samples, PAH concentrations declined sharply over time, suggesting rapid absorption by corals or degradation through physical-chemical processes. The detection of PAHs even in control groups (tissue and skeleton) indicates potential prior environmental exposure. Overall, M. hispida demonstrated a strong capacity to bioaccumulate PAHs, underscoring its vulnerability and value as a sentinel species for monitoring contamination in tropical reef ecosystems, particularly in regions affected by oil exploration and production.
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This study evaluated the effects of dietary supplementation with microencapsulated organic acids and phenolic compounds in laying hens. The experiment was conducted with 500 Novogen Brown laying hens from 30 weeks of age. Birds were assigned to five treatments with 10 replicates of 10 birds each in a completely randomized design. The treatments consisted of: CD = control diet; 200AD1 = 200 g/t additive 1; 500AD1 = 500 g/t additive 1; 200AD2 = 200 g/t additive 2; and 500AD2 = 500 g/t additive 2. Productive performance, egg quality, organ pH and relative organ weight, intestinal histomorphometry, and serum biochemical parameters were evaluated. Treatment means were compared using the Tukey test at a 5% significance level. Dietary supplementation affected productive performance, egg quality, gastrointestinal morphology, and selected serum biochemical indicators. Birds receiving 500AD1 and 500AD2 showed higher egg production compared with those receiving 200AD2, whereas egg weight was lower in 500AD2 compared with 200AD1. Egg quality traits were also influenced, with greater eggshell thickness observed in 200AD2 and improved yolk index in 200AD2 and 500AD2 compared with the control diet. Relative weights of digestive organs, including gizzard, small intestine, pancreas, and proventriculus, were generally higher in birds receiving 200AD2. Cecal pH was reduced in 500AD1 compared with the other treatments. Intestinal histomorphometry showed significant alterations in villus structure, absorptive area, and goblet cell counts across intestinal segments, with 500AD2 frequently associated with higher villus:crypt ratios and greater ileal villus height. Serum biochemical parameters were also affected, including uric acid, γ-glutamyl transferase, calcium, and phosphorus. In summary, supplementation with microencapsulated organic acids and phenolic compounds modulated productive performance, egg quality, and intestinal physiology in laying hens. Higher inclusion levels, particularly 500AD2, were associated with more favorable intestinal morphometric responses and productive outcomes, whereas 200AD2 appeared to promote structural adaptations of the gastrointestinal tract. These findings highlight the potential of microencapsulated acidifier phytogenic blends as nutritional strategies to support intestinal functionality and productive efficiency in laying hens.
Eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES) are rare systemic inflammatory diseases with overlapping features. Mepolizumab, a humanized mAb targeting IL-5, has been approved for treatment of both conditions. However, real-world data on its clinical benefit in private practice settings remain limited. We sought to evaluate oral corticosteroid (OCS) use, clinical outcomes, and end-organ manifestations post-mepolizumab initiation in private practice settings using electronic medical records. This retrospective pre-post cohort study used data from the US-based Allergy Partners network electronic medical records (January 1, 2007, to August 17, 2023) to select patients with EGPA or HES who initiated mepolizumab (index date). Participants were 18 years and older (EGPA) or 12 years and older (HES) with 3 or more months of clinical activity pre- and postindex. Outcomes included OCS use and dose, clinical outcomes (response and remission), and end-organ damage manifestations. Overall, 44 patients with EGPA and 16 patients with HES had significant reductions in OCS use and dose (P = .014 for trend over each 6-month period), with improvements in end-organ manifestations over a treatment period up to 2 years. Among patients with EGPA, clinical response, disease control, and remission rates increased significantly. In addition, 86.4% of patients with EGPA experienced an improvement in at least 1 of the outcome measures of OCS use, end-organ manifestations, or blood eosinophil count. Among patients with HES, end-organ manifestations were more common preindex (87.5%) than postindex (56.3%). These findings highlight the long-term OCS-sparing effects of mepolizumab and suggest additional clinical benefits for patients with EGPA and HES in a private practice setting.
HLA-DRB1*13:370N differs from the HLA-DRB1*13:01:01:01 allele by a deletion of two nucleotides in exon 2.
Clostridioides difficile infection (CDI), primarily mediated by toxin B (TcdB), is a leading cause of healthcare-associated and community-acquired diarrhea worldwide. Although this genus exhibits substantial genomic diversity, functional studies have focused mainly on a limited set of isolates, leaving other genomospecies understudied in this regard. Here, we characterized five isolates derived from five distinct patients with suspected CDI cases that tested negative for the tcdC PaLoc marker. Integrated genomic, proteomic, and phenotypic analyses confirm that these strains constitute three novel toxin-producing species and their distinct carbon utilization profiles, exoproteomes, and spore protein repertoires suggest niche specialization within the human gut ecosystem. These species harbor monotoxin PaLoc architectures encoding TcdB7 or TcdB11, located on either chromosomal or extrachromosomal elements, which frequently co-occur with binary toxin loci. Functional assays confirmed secretion of active TcdB, cytotoxicity in mammalian cells, and moderate enterotoxicity in a murine ileal loop model, although virulence was attenuated relative to C. difficile R20291 from Clade 2. Collectively, these findings expand the taxonomy of toxigenic Clostridioides, highlight the dynamic evolution of TcdB-mediated pathogenicity, and emphasize the importance of refining diagnostic workflows and surveillance strategies to address emerging diarrheal diseases. The three novel species were designated as Clostridioides cryptodifficilis sp. nov., Clostridioides divergens sp. nov., and Clostridioides subdifficilis sp. nov.
ObjectivesChronic venous disease (CVD) is a progressive condition affecting the lower limb venous system, leading to venous hypertension, muscle dysfunction, and gait alterations. Patients with CVD often experience muscle weakness, reduced ankle mobility, and impaired gait biomechanics. However, the impact of CVD severity on spatiotemporal gait parameters and plantar flexor strength remains little explored. The present study aimed to compare gait biomechanics, plantar flexor strength, dorsiflexion ankle range of motion, and functional performance among patients with mild, moderate, and severe CVD, classified according to the CEAP system.MethodsA cross-sectional study was conducted in two phases. Phase 1 compared gait parameters between healthy individuals and patients with CVD. Phase 2 examined variations in movement patterns across CVD severity groups, classified according to CEAP class into mild CVD (CEAP 1; n = 11), moderate CVD (CEAP 2-3; n = 12), and severe CVD (CEAP 4-6; n = 6). Gait parameters, including speed, stride length, and stance time, were assessed using a motion capture system. Plantar flexor strength was measured with a handheld dynamometer. Ankle dorsiflexion range of motion was assessed using the Weight-Bearing Lunge Test (WBLT), and functional performance was evaluated using the Human Activity Profile (HAP) questionnaire.ResultsNo significant differences were observed in spatiotemporal gait parameters between healthy individuals and patients with CVD or across disease severity groups. In contrast, normalized plantar flexor strength differed significantly among groups (p = .041). Ankle dorsiflexion range of motion was also reduced with increasing disease severity (p = .005), particularly in the severe group. No significant differences were found for HAP scores.ConclusionCVD severity was associated with reduced plantar flexor strength and ankle dorsiflexion range of motion, while spatiotemporal gait parameters remained unchanged. These findings suggest that musculoskeletal impairments may precede detectable alterations in gait, highlighting the importance of early assessment and targeted rehabilitation strategies in patients with CVD.
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There has been a significant increase in the surgical procedures for breast implant removal and capsulectomies, primarily because of the fear that implants may cause cancer, breast implant-related illness (BII), or systemic symptoms associated with breast implants (SSBI). We conducted a systematic review and meta-analysis according to PRISMA criteria. The main objective of the study was to identify the causes of explantation and capsulectomy and whether the procedure improves the alterations attributable to breast implants. We did not include patients diagnosed with BIA-ALCs in this study. We divided the patients into two groups: the first comprised BII/SSBI and ASIA syndrome; the second group comprised granulomas, hypercalcemia, renal damage, and respiratory dysfunction. After explantation and capsulectomy, most patients in the first group did not achieve complete improvement and the degree was moderate, whereas patients in the second group achieved significant improvement. The patients with ASIA achieved partial improvement and required additional treatment. We found significant differences in the symptoms between BII/SSBI and ASIA. The incidence of breast implant-associated comorbidities was not related to the implant length of stay, capsular contracture, or rupture; age < 50 years was a significant factor in the incidence of BII/SSBI. There was considerable heterogeneity in the literature; therefore, the results of this study should be interpreted with caution.
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Low tidal volume (Vt) ventilation is the standard of care among critically ill patients. Guidelines recommend scaling Vt to the predicted body weight (PBW) to avoid ventilator-induced lung injury (VILI). Concerns exist that the PBW overestimates lung volumes of critically ill females. We investigated whether this applies to clinically relevant measures of lung volume, whether PBW-guided mechanical ventilation yields comparable risk of lung stress among male and female patients, and whether this affects mortality. Mechanically ventilated, critically ill patients from ten randomized trials and two real-world retrospective clinical datasets were analyzed. Risk of high driving pressures (≥ 15 cmH2O) at comparable Vt/kg PBW as well as measures of anatomical and functional lung sizes, including computed tomography-measured lung volumes at the same PBW were compared between female and male patients. Among 30,516 patients (39.4% female), ventilation with comparable tidal volumes standardized to PBW (ml/kg PBW) was associated with 4.2% (95% CI 3.2-5.3; aOR 1.26, 95% CI 1.19-1.33; p < 0.001) higher absolute risk of high driving pressures among females, mediating 8.4% of excess 28-day mortality (p < 0.001). At the same PBW, female patients had lower anatomical and aerated lung volumes (- 343 ml, 95% CI - 449 to - 237, p < 0.001; and - 188, 95% CI - 282 to - 94, p < 0.001, respectively) than males. The widely used PBW equation overestimates lung volumes in female critically ill patients, resulting in excess risk of injurious driving pressures among females, mediating higher mortality. Personalized mechanical ventilation by using driving pressure-guided strategies might mitigate these disparities.
There are no official data on the prevalence of end-stage chronic kidney disease with dialysis for the Brazilian state of Pará. To describe the clinical-epidemiological profile of hemodialysis patients at the largest specialist center in the state of Pará. This is an observational, cross-sectional, descriptive, quantitative study. Simple descriptive statistics were calculated. Data were collected from medical records from June to August 2022 at the Hemodialysis Center at the Hospital de Clínicas Gaspar Vianna (HCGV) and the Monteiro Leite Hemodialysis Clinic (CMHL), both in Belém, Pará, Brazil. A total of 191 patients from the chronic hemodialysis program were interviewed. Of the total sample, 28.8% patients were from HCGV and 71.6% from CHML; 57.1% were men and 42.9% were women. Mean age was 54.1 years. Results showed that 65.4% of patients self-reported skin color as brown, 44.5% had completed primary education, 41.9% were single, 71.4% had hypertension, 40.6% had diabetes, and 77.5% had been on renal replacement therapy for a mean time of 4 years. Regarding treatment, 86.9% started treatment with a short-duration catheter, 8.4% were using a long-dwelling catheter, and 4.7% had a definitive dialysis access via a mature arteriovenous fistula (AVF). Currently, 58.1% of these patients have a native AVF, 34% have a long-dwelling catheter, and 3.1% have a short-duration catheter and no AVF. Patients on renal replacement therapy in Pará predominantly initiate hemodialysis in an unplanned manner, using temporary venous catheters, although they transition to definitive vascular access over time. This scenario highlights the need for early diagnosis of chronic kidney disease and timely vascular access planning, aiming to reduce complications and optimize clinical outcomes. No estado do Pará, não há dados oficiais quanto à prevalência de doença renal crônica terminal em diálise. Descrever o perfil clínico-epidemiológico dos pacientes em hemodiálise no maior centro de referência do Pará. Trata-se de um estudo observacional, transversal, descritivo e quantitativo. Foi realizada estatística descritiva simples. Os dados foram coletados por meio de prontuários, de junho a agosto de 2022, no Centro de Hemodiálise do Hospital de Clínicas Gaspar Vianna (HCGV) e na Clínica de Hemodiálise Monteiro Leite (CHML), ambos em Belém (PA). Foram entrevistados 191 pacientes do programa crônico de hemodiálise. Dos entrevistados, 28,8% eram pacientes do HCGV e 71,6%, do CHML. Desses, 57,1% eram homens e 42,9%, mulheres. A média de idade foi de 54,1 anos. Entre os resultados observados, 65,4% se autodeclararam pardos, 44,5% completaram o ensino fundamental, 41,9% eram solteiros, 71,4% eram hipertensos, 40,6% eram diabéticos e 77,5% tinham média de 4 anos em terapia renal substitutiva. Em relação ao tratamento, 86,9% iniciaram a terapia por cateter de curta duração, 8,4% utilizaram o de longa permanência e 4,7% apresentaram o acesso definitivo com uma fístula arteriovenosa (FAV) maturada. Atualmente, 58,1% dos pacientes apresentam FAV nativa, 34% têm cateter de longa permanência e 3,1% possuem cateter de curta duração e sem FAV. Pacientes em terapia renal substitutiva no Pará iniciam a hemodiálise predominantemente de forma não planejada, por meio de cateteres venosos temporários, embora evoluam para acessos definitivos ao longo do seguimento. Esse cenário evidencia a necessidade de diagnóstico precoce da DRC e planejamento antecipado do acesso vascular, visando reduzir complicações e otimizar os desfechos clínicos.
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The aquatic biota of the Amazon is subject to considerable daily and seasonal fluctuations in its environment. The ability to adapt to changes in the environment, such as increased water temperatures, is essential for the survival and physiological performance of these organisms. The anticipated rise in temperature and CO2 levels, projected to reach 6 °C and 50% above current levels by the end of the century, respectively, represents a significant and imminent threat to aquatic biodiversity. The objective of this study was to assess the effects of acute short-term exposure to elevated temperature on the brain mitochondrial respiration of two Amazonian fish species with contrasting trophic roles: Schizodon fasciatus, which represents a prey species at a lower trophic level, and Pygocentrus nattereri, a predatory species. Specimens of Schizodon fasciatus and Pygocentrus nattereri were collected and subjected to temperatures of 28 °C and 37 °C for a period of four hours. Brain mitochondrial respiration was quantified to analyze complexes I, I + II, III, IV, proton leak (H+Leak), RCR, and ETS. Additionally, the production of reactive oxygen species (ROS) was evaluated. The results revealed that exposure to higher temperatures caused elevated complex I activity in both species, with a more pronounced increase observed in S. fasciatus. Furthermore, significant increases in complex I + II and complex III were observed in S. fasciatus, while complex IV showed a decrease in both species. H+Leak exhibited a decrease in P. nattereri, whereas RCR demonstrated an increase in both species. ROS production displayed a decrease in P. nattereri but remained stable in S. fasciatus. The findings suggest that both fish species possess the capacity to adapt their brain mitochondrial function to higher temperatures, albeit with species-specific responses. These adaptations assist in maintaining brain energy production and minimizing oxidative stress, and emphasize potential imbalances in predator-prey relationships under changing environmental conditions.
Formaldehyde remains widely used as a fixative despite its documented risks. Ethanol-based fixatives have emerged as safer alternatives, but their performance in urogenital tissues has not been systematically assessed. To compare the histomorphological preservation of rat kidneys, prostate, penis, and testis fixed with ethanol versus formaldehyde-based solutions. Six adult male rats were euthanized, and urogenital organs were collected and sectioned. Testes were initially fixed in Bouin's solution for 24h. All tissues were subsequently immersed in buffered formaldehyde (BF), buffered paraformaldehyde (BP), 70% unbuffered ethanol (UE), or 70% buffered ethanol (BE) for 96h (or 72h for testes following Bouin). Samples were processed for paraffin embedding and stained with H&E. Four blinded examiners scored tissue preservation, staining quality, and artifacts using a 1-5 scale. Data were analyzed using Kruskal-Wallis with Dunn's post-test (p<0.05). Ethanol-based fixatives (UE and BE) consistently outperformed aldehyde-based fixatives (BF and BP). In kidneys, UE and BE yielded fewer artifacts and superior preservation of glomerular and tubular structures. In the prostate, these fixatives provided better epithelial and stromal quality and fewer artifacts. All fixatives adequately preserved penile cavernous tissue, but BE showed superior urothelial integrity. Following Bouin's pre-fixation, UE and BE improved staining and preservation of the germinal epithelium and Sertoli cells compared with aldehyde fixatives. Ethanol-based fixatives provide superior or comparable histomorphological preservation of urogenital tissues while avoiding the health and environmental risks associated with formaldehyde.
We report a rare case of non-secretory multiple myeloma (NSMM) presenting with marked eosinophilia and considerable diagnostic difficulty. A 56-year-old man was admitted with recurrent low back pain of more than 10 years' duration that had rapidly worsened over the preceding 10 days, accompanied by diffuse pain and weight loss. Laboratory evaluation showed persistent eosinophilia, thrombocytopenia, elevated lactate dehydrogenase, and increased inflammatory markers. Imaging revealed multifocal osteolytic lesions involving the skull, vertebrae, ribs, and pelvis. However, serum and urine immunofixation electrophoresis were negative, qualitative urine Bence-Jones protein testing was negative, and repeated serum free light chain testing showed a normal κ/λ ratio, making the diagnosis particularly challenging. Bone marrow aspirate showed marked eosinophilia, and flow cytometry identified clonal plasma cells accounting for 6.1% of nucleated cells. Bone marrow biopsy with immunohistochemistry confirmed a plasma-cell neoplasm, while myeloma fluorescence in situ hybridization (FISH) revealed 1q21 gain/amplification together with chromosome 13-related abnormalities, including RB1 deletion and D13S319 abnormality. After exclusion of secondary and primary/clonal eosinophilic disorders, the patient was diagnosed with NSMM with eosinophilia. This case highlights the diagnostic challenge posed by the coexistence of marked eosinophilia and NSMM, which obscured the underlying plasma-cell malignancy despite repeatedly negative monoclonal protein studies. We also reviewed the limited literature on MM-associated eosinophilia to underscore the importance of integrating bone marrow findings, imaging, and cytogenetic evaluation in atypical cases.
Dengue is classified into mild dengue, which is treated at outpatient clinics, dengue with warning signs (WS+), which requires hospitalization, and severe dengue, which can be fatal. It is assumed that severe manifestations result from uncontrolled immune activation. Regulatory T cells (Tregs) are crucial for controlling inflammation in various diseases, but are poorly studied in dengue. This study aimed to investigate the Tregs phenotype in different clinical forms of dengue infection. Plasma and peripheral blood mononuclear cells (PBMCs) were collected from healthy donors and dengue patients. PBMCs were cultured in the presence of peptide libraries encoding the envelope (ENV) and NS3 viral proteins of DENV1. WS+ dengue patients presented higher plasma IL-10 levels than mild dengue during the febrile phase. In contrast, mild cases displayed a balanced proinflammatory and regulatory cytokine profile with high levels of IFNγ, TNF, and IL-10 in the plasma compared to WS+ group during the critical phase. Mild dengue patients also showed higher frequencies of Tregs with increased expression of GITR (Glucocorticoid-Induced TNFR-Related) and CD200 when compared with WS+ dengue, both in critical and convalescent phases. In contrast, frequencies of PD1+ Tregs, which can indicate Tregs dysfunction, were increased in WS+ dengue subjects. Importantly, DENV-specific GITR+ Tregs were a source of IL-10 in mild dengue, but this population was absent from WS+ patients. While WS+ dengue patients presented altered regulatory phenotypes by Tregs, the presence of IL-10 by DENV-specific GITR+ Tregs and CD200+ Tregs was associated with mild presentation of dengue, suggesting that these regulatory mechanisms play an important role in limiting dengue immunopathology.
Attention-deficit/hyperactivity disorder (ADHD) is linked to heightened risk-taking tendencies. Core symptoms and traits, such as impulsivity, hyperactivity, and risk-taking, stem from dysfunctions in frontostriatal circuitry. The endocannabinoid system (ECS) modulates frontostriatal dynamics and monoaminergic signaling. The pair of strains, spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) rats, is an established model for ADHD. The endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA) impact defensive behaviors by fine-tuning neural circuits involved in threat detection and response. This study explores how enhancing 2-AG and AEA levels shapes defensive behavior in approach-avoidance paradigms using the open field and elevated plus maze tasks. We also investigated strain- and sex-related differences in CB1R, CB2R, FAAH, and MAGL protein content in brain regions implicated in executive function, including the prefrontal cortex (PFC), striatum (STR), and hippocampus (HP). A MAGL inhibitor enhanced risk assessment in WKY rats. Female rats exhibited reduced stretch-attend posture (SAP) when endocannabinoid ligand levels were elevated. Specifically, in the SHR strain, males showed increased head dipping (HD) with a FAAH inhibitor, whereas females exhibited the opposite pattern. SHR females exhibited increased HD following administration of an AEA transport inhibitor. Basal protein content analysis showed that in the STR, female SHRs had higher FAAH and MAGL levels than female WKY rats, while male SHRs had lower CB2R levels. In the HP, CB2R content was elevated in female SHRs compared to WKYs. Both WKY and SHR females showed reduced PFC CB1R content relative to their male counterparts. In SHRs, females exhibited higher FAAH levels in the STR and HP, and lower CB2R in the HP, compared to males. These findings indicate that increasing 2-AG and AEA by inhibiting their degradation pathways modulates defensive behavior in a strain- and sex-dependent manner. Differences in protein expression within the PFC, STR, and HP align with behavioral outcomes, providing molecular insight into strain- and sex-specific patterns of defensive behavior.