Managing medications among individuals with mild cognitive impairment and dementia: Patient-caregiver perspectives.

BACKGROUND: With changing cognitive abilities, individuals with mild cognitive impairment (MCI) and dementia face challenges in successfully managing multidrug regimens. We sought to understand how individuals with MCI or dementia and their family caregivers manage multidrug regimens and better understand patient-to-caregiver transitions in medication management responsibilities. METHODS: We conducted qualitative interviews among patient-caregiver dyads. Eligibility included: patients with a diagnosis of MCI, mild or moderate dementia, managing ≥3 chronic conditions, ≥5 prescription medications, who also had a family caregiver ≥18 years old. Semi-structured interview guides, informed by the Medication Self-Management model, ascertained roles and responsibilities for medication management and patient-to-caregiver transitions in medication responsibilities. RESULTS: We interviewed 32 patient-caregiver dyads. Older adults and caregivers favored older adult autonomy in medication management, and individuals with MCI and mild dementia largely managed their medications independently using multiple strategies (e.g., establishing daily routines, using pillboxes). Among individuals with moderate dementia, caregivers assumed all medication-related responsibilities except when living separately. In those scenarios, caregivers set up organizers and made reminder calls, but did not observe family members taking medications. Patient-to-caregiver transitions in medication responsibilities frequently occurred after caregivers observed older adults making errors with medications. As caregivers sought to assume greater responsibilities with family members' medicines, they faced multiple barriers. Most barriers were dyadic; they affected both the older adult and the caregiver and/or the relationship. Some barriers were specific to caregivers; these included caregivers' competing responsibilities or inaccurate perceptions of dementia, while other barriers were related to the healthcare system. CONCLUSIONS: To ease medication management transitions, balance must be sought between preservation of older adult autonomy and early family caregiver involvement. Clinicians should work to initiate conversations with family caregivers and individuals living with MCI or dementia about transitioning medication responsibilities as memory loss progresses, simplify regimens, and deprescribe, as appropriate.

Comparison of Outcomes in Bowel Resections by Gynecologic Oncologists Versus General Surgeons During Maximal Cytoreductive Surgery for Advanced Ovarian Cancer: Gynecologic Oncology Research Investigators Collaboration Study (GORILLA-3006).

BACKGROUND: This report describes the oncologic outcomes for patients with advanced ovarian cancer who had bowel surgery performed by gynecologic oncologists (GOs) and compares the outcomes with those for bowel surgery performed by general surgeons (GSs) during maximal cytoreductive surgery. METHODS: Patients from six academic institutions who had FIGO stage III or IV ovarian cancer and underwent any bowel surgeries during maximal cytoreductive surgery were eligible for the study. The patients were divided into two groups according to whether bowel surgery was performed by a GO or a GS. In both groups, the GOs were mainly involved in extra bowel debulking procedures. Perioperative and survival outcomes were compared between the two groups. RESULTS: The 761 patients in this study included 113 patients who underwent bowel surgery by a GO and 648 who had bowel surgery by a GS. No discernible differences were observed in age, American Society of Anesthesiology (ASA) score, FIGO stage, histologic type, timing of cytoreductive surgery (primary or interval debulking surgery), or complications between the two groups. The GO group exhibited a shorter operation time than the GS group. Kaplan-Meier analysis showed no survival differences between the two groups. In the Cox analysis, non-serous cell types and gross residual diseases were associated with adverse effects on overall survival. However, performance of bowel surgery by a GO did not have an impact on survival. CONCLUSION: Performance of bowel surgery by a GO during maximal cytoreductive surgery is both feasible and safe. These results should be reflected in the training system for GOs regarding bowel surgery, and further research is needed to confirm that GOs can play a more leading role in performing extra-uterine procedures.

Terrestrial laser scanning and low magnetic field digitization yield similar architectural coarse root traits for 32-year-old Pinus ponderosa trees.

BACKGROUND: Understanding how trees develop their root systems is crucial for the comprehension of how wildland and urban forest ecosystems plastically respond to disturbances such as harvest, fire, and climate change. The interplay between the endogenously determined root traits and the response to environmental stimuli results in tree adaptations to biotic and abiotic factors, influencing stability, carbon allocation, and nutrient uptake. Combining the three-dimensional structure of the root system, with root morphological trait information promotes a robust understanding of root function and adaptation plasticity. Low Magnetic Field Digitization coupled with AMAPmod (botAnique et Modelisation de l'Architecture des Plantes) software has been the best-performing method for describing root system architecture and providing reliable measurements of coarse root traits, but the pace and scale of data collection remain difficult. Instrumentation and applications related to Terrestrial Laser Scanning (TLS) have advanced appreciably, and when coupled with Quantitative Structure Models (QSM), have shown some potential toward robust measurements of tree root systems. Here we compare, we believe for the first time, these two methodologies by analyzing the root system of 32-year-old Pinus ponderosa trees. RESULTS: In general, at the total root system level and by root-order class, both methods yielded comparable values for the root traits volume, length, and number. QSM for each root trait was highly sensitive to the root size (i.e., input parameter PatchDiam) and models were optimized when discrete PatchDiam ranges were specified for each trait. When examining roots in the four cardinal direction sectors, we observed differences between methodologies for length and number depending on root order but not volume. CONCLUSIONS: We believe that TLS and QSM could facilitate rapid data collection, perhaps in situ, while providing quantitative accuracy, especially at the total root system level. If more detailed measures of root system architecture are desired, a TLS method would benefit from additional scans at differing perspectives, avoiding gravitational displacement to the extent possible, while subsampling roots by hand to calibrate and validate QSM models. Despite some unresolved logistical challenges, our results suggest that future use of TLS may hold promise for quantifying tree root system architecture in a rapid, replicable manner.

Conceptualizing Student Experiences of Psychological Safety in Simulation: A Grounded Theory Study.

BACKGROUND: Simulation-based learning activities have become more prevalent in prelicensure nursing curricula. When following the Simulation Standards of Best Practice, optimal learning conditions can be achieved, including the creation of a psychologically safe learning environment. Yet, the process of how students come to feel psychologically safe during a simulation experience remains unknown. METHOD: A grounded theory approach was used to conceptualize the basic social process by which nursing students feel psychologically safe during a simulation learning experience. RESULTS: Six categories emerged from the data: (1) being nervous; (2) having a good instructor; (3) learning; (4) coming together; (5) being in debriefing; and (6) leaving on a positive note. The core category of putting myself out there emerged as the basic social process. CONCLUSION: The social process of psychological safety in simulation develops within nursing students as the result of interplay among several dimensions of the learning experience. [J Nurs Educ. 2024;63(7):427-433.].

Why Evidence Generation Should Matter to Payers and How They Can Help.

Importance: The US leads the world in bringing new medical products to market, but the ability to generate evidence to inform clinical practice in postmarket settings needs improvement. Although a diverse group of stakeholders is working to improve postmarket evidence generation, the role of private payers has been underappreciated. Observations: Payers are crucial allies in improving evidence generation because better data would better inform coverage decisions, their policies and practices influence the conduct of care and research, and their claims data are a source of real-world evidence used in medical product evaluation. In addition, payers have a stake in improving evidence generation because the kinds of evidence needed to inform health care and coverage decisions are often not available when a product enters the market and may not be generated without their involvement. Here, we describe several key steps payers could take to improve evidence generation, including participating in efforts to reduce administrative and financial barriers to the conduct of clinical trials, directly incentivizing evidence generation on high-priority questions by funding potential cost-saving trials, increasing engagement with the medical products industry on evidentiary needs for coverage decisions, and improving usability of claims data by reducing data lags and routinely recording unique device identifiers. Broad payer engagement with US Food and Drug Administration recommendations regarding evidence generation will ensure that the opportunities to participate in clinical research are extended to all communities and that evidence needed to inform care is generated in trials and surveillance systems that reflect the clinical reality across the US. Conclusions and Relevance: Increasing payer involvement in evidence generation can benefit all participants in the medical innovation ecosystem. The importance of payers in these efforts will continue to grow in response to imperatives to increase integration of care and research, engage a diverse set of communities in clinical research, and move toward alternative payment models.

VCP/p97-associated proteins are binders and debranching enzymes of K48-K63-branched ubiquitin chains.

Branched ubiquitin (Ub) chains constitute a sizable fraction of Ub polymers in human cells. Despite their abundance, our understanding of branched Ub function in cell signaling has been stunted by the absence of accessible methods and tools. Here we identify cellular branched-chain-specific binding proteins and devise approaches to probe K48-K63-branched Ub function. We establish a method to monitor cleavage of linkages within complex Ub chains and unveil ATXN3 and MINDY as debranching enzymes. We engineer a K48-K63 branch-specific nanobody and reveal the molecular basis of its specificity in crystal structures of nanobody-branched Ub chain complexes. Using this nanobody, we detect increased K48-K63-Ub branching following valosin-containing protein (VCP)/p97 inhibition and after DNA damage. Together with our discovery that multiple VCP/p97-associated proteins bind to or debranch K48-K63-linked Ub, these results suggest a function for K48-K63-branched chains in VCP/p97-related processes.

Fragment-Based Discovery of a Series of Allosteric-Binding Site Modulators of ß-Glucocerebrosidase.

ß-Glucocerebrosidase (GBA/GCase) mutations leading to misfolded protein cause Gaucher's disease and are a major genetic risk factor for Parkinson's disease and dementia with Lewy bodies. The identification of small molecule pharmacological chaperones that can stabilize the misfolded protein and increase delivery of degradation-prone mutant GCase to the lysosome is a strategy under active investigation. Here, we describe the first use of fragment-based drug discovery (FBDD) to identify pharmacological chaperones of GCase. The fragment hits were identified by using X-ray crystallography and biophysical techniques. This work led to the discovery of a series of compounds that bind GCase with nM potency and positively modulate GCase activity in cells.

Neoadjuvant talazoparib in patients with germline BRCA1/2 mutation-positive, early-stage triple-negative breast cancer: exploration of tumor BRCA mutational status.

BACKGROUND: Talazoparib monotherapy in patients with germline BRCA-mutated, early-stage triple-negative breast cancer (TNBC) showed activity in the neoadjuvant setting in the phase II NEOTALA study (NCT03499353). These biomarker analyses further assessed the mutational landscape of the patients enrolled in the NEOTALA study. METHODS: Baseline tumor tissue from the NEOTALA study was tested retrospectively using FoundationOne®CDx. To further hypothesis-driven correlative analyses, agnostic heat-map visualizations of the FoundationOne®CDx tumor dataset were used to assess overall mutational landscape and identify additional candidate predictive biomarkers of response. RESULTS: All patients enrolled (N = 61) had TNBC. In the biomarker analysis population, 75.0% (39/52) and 25.0% (13/52) of patients exhibited BRCA1 and BRCA2 mutations, respectively. Strong concordance (97.8%) was observed between tumor BRCA and germline BRCA mutations, and 90.5% (38/42) of patients with tumor BRCA mutations evaluable for somatic-germline-zygosity were predicted to exhibit BRCA loss of heterozygosity (LOH). No patients had non-BRCA germline DNA damage response (DDR) gene variants with known/likely pathogenicity, based on a panel of 14 non-BRCA DDR genes. Ninety-eight percent of patients had TP53 mutations. Genomic LOH, assessed continuously or categorically, was not associated with response. CONCLUSION: The results from this exploratory biomarker analysis support the central role of BRCA and TP53 mutations in tumor pathobiology. Furthermore, these data support assessing germline BRCA mutational status for molecular eligibility for talazoparib in patients with TNBC.

Machine-learning-based integrative -'omics analyses reveal immunologic and metabolic dysregulation in environmental enteric dysfunction.

Environmental enteric dysfunction (EED) is a subclinical enteropathy challenging to diagnose due to an overlap of tissue features with other inflammatory enteropathies. EED subjects (n = 52) from Pakistan, controls (n = 25), and a validation EED cohort (n = 30) from Zambia were used to develop a machine-learning-based image analysis classification model. We extracted histologic feature representations from the Pakistan EED model and correlated them to transcriptomics and clinical biomarkers. In-silico metabolic network modeling was used to characterize alterations in metabolic flux between EED and controls and validated using untargeted lipidomics. Genes encoding beta-ureidopropionase, CYP4F3, and epoxide hydrolase 1 correlated to numerous tissue feature representations. Fatty acid and glycerophospholipid metabolism-related reactions showed altered flux. Increased phosphatidylcholine, lysophosphatidylcholine (LPC), and ether-linked LPCs, and decreased ester-linked LPCs were observed in the duodenal lipidome of Pakistan EED subjects, while plasma levels of glycine-conjugated bile acids were significantly increased. Together, these findings elucidate a multi-omic signature of EED.

Patient Preferences for Out-of-Hospital Cardiac Arrest Care in South Africa: A Discrete Choice Experiment.

OBJECTIVE: This study examined the trade-offs low-resource setting community members were willing to make in regard to out-of-hospital cardiac arrest care using a discrete choice experiment survey. METHODS: We administered a discrete choice experiment survey to a sample of community members 18 years or older across South Africa between April and May 2022. Participants were presented with 18 paired choice tasks comprised of 5 attributes (distance to closest adequate facility, provider of care, response time, chances of survival, and transport cost) and a range of 3 to 5 levels. We used mixed logit models to evaluate respondents' preferences for selected attributes. RESULTS: Analyses were based on 2228 responses and 40 104 choice tasks. Patients valued care with the shortest response time, delivered by the highest qualified individuals, which placed them within the shortest distance of an adequate facility, gave them the highest chance of survival, and costed the least. In addition, patients preferred care delivered by their family members over care delivered by the lay public. The highest mean willingness-to-pay for increased survival is 11 699 South African rand (ZAR), followed by distance to health facility (8108 ZAR), and response time (5678 ZAR), and the lowest for increasing specialization of provider (1287 ZAR). CONCLUSIONS: In low-resource settings, it may align with patients' preference to include targeted resuscitation training for family members of individuals with high-risk for cardiac arrest as a part of out-of-hospital cardiac arrest intervention strategies.

The Role of Pancreatitis Risk Genes in Endocrine Insufficiency Development After Acute Pancreatitis in Children.

BACKGROUND & AIMS: Acute pancreatitis (AP) is increasingly recognized as a risk factor for diabetes mellitus (DM). We aimed to study the association of pancreatitis genes with pancreatic endocrine insufficiency (pre-DM and DM) development post-AP in children. METHODS: This was an observational cohort study that enrolled subjects ≤21 years with their first episode of AP and followed them for 12 months for the development of pancreatic endocrine insufficiency. Pancreatitis risk genes (CASR, CEL, CFTR, CLDN2, CPA1, CTRC, PRSS1, SBDS, SPINK1, and UBR1) were sequenced. A genetic risk score was derived from all genes with univariable P < .15. RESULTS: A total 120 subjects with AP were genotyped. Sixty-three subjects (52.5%) had at least 1 reportable variant identified. For modeling the development of pancreatic endocrine insufficiency at 1 year, 6 were excluded (2 with DM at baseline, 3 with total pancreatectomy, and 1 death). From this group of 114, 95 remained normoglycemic and 19 (17%) developed endocrine insufficiency (4 DM, 15 pre-DM). Severe AP (58% vs 20%; P = .001) and at least 1 gene affected (79% vs 47%; P = .01) were enriched among the endocrine-insufficient group. Those with versus without endocrine insufficiency were similar in age, sex, race, ethnicity, body mass index, and AP recurrence. A model for pre-DM/DM development included AP severity (odds ratio, 5.17 [1.66-16.15]; P = .005) and genetic risk score (odds ratio, 4.89 [1.83-13.08]; P = .002) and had an area under the curve of 0.74. CONCLUSIONS: In this cohort of children with AP, pancreatitis risk genes and AP disease severity were associated with pre-DM or DM development post-AP.

How relations between early reading skills and third-grade mathematics outcomes vary across distribution: A quantile regression approach.

Early reading skills are critical for later academic outcomes, which include mathematics. Yet, these relations may vary by a child's ability level. This study examined how early reading skills relate to different levels of third-grade mathematics. The samples included 105 same-sex twin pairs (210 individuals, 57% female, 43% male) from the ongoing longitudinal Western Reserve Reading and Math Projects, assessed at kindergarten (M = 6.18, SD = 0.44) and third grade (M = 9.07, SD = 0.49). Kindergarten reading measures consisted of the Letter Identification task from the Woodcock Reading Mastery Test-Revised Normative Update, the Deletion subtests from Phonological Awareness Test, and the Letter Naming Fluency task from the Dynamic Indicators of Basic Early Literacy Skills; third-grade math measures included Calculation, Fluency, Applied Problem, and Quantitative Concepts subtests of Woodcock-Johnson III Tests of Achievement. Both linear and quantile regressions were conducted using reading measures as predictors and math measures as the dependent variables. Linear regressions indicated that the Deletion Summary Score was a unique predictor of Applied Problems, and Letter Naming Fluency was a significant and unique predictor of Calculation Fluency and Quantitative Concepts. Quantile regressions provided a more thorough analysis of these relations. It was found that Letter Naming Fluency was significantly associated with Calculation, Calculation Fluency, and Quantitative Concepts at the lower level. The Deletion Summary Score had relatively stable relations with Applied Problems across all levels. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

ACR Appropriateness Criteria® Acute Pelvic Pain in the Reproductive Age Group: 2023 Update.

This review focuses on the initial imaging in the reproductive age adult population with acute pelvic pain, including patients with positive and negative beta-human chorionic gonadotropin (ß-hCG) levels with suspected gynecological and nongynecological etiology. For all patients, a combination of transabdominal and transvaginal pelvic ultrasound with Doppler is usually appropriate as an initial imaging study. If nongynecological etiology in patients with negative ß-hCG is suspected, then CT of the abdomen and pelvis with or without contrast is also usually appropriate. In patients with positive ß-hCG and suspected nongynecological etiology, CT of the abdomen and pelvis with contrast and MRI of the abdomen and pelvis without contrast may be appropriate. In patients with negative ß-hCG and suspected gynecological etiology, CT of the abdomen and pelvis with contrast, MRI of pelvis without contrast, or MRI of pelvis with and without contrast may be appropriate. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Ileal Crohn's Disease Exhibits Reduced Activity of Phospholipase C-ß3-Dependent Wnt/ß-Catenin Signaling Pathway.

Crohn's disease is a chronic, debilitating, inflammatory bowel disease. Here, we report a critical role of phospholipase C-ß3 (PLC-ß3) in intestinal homeostasis. In PLC-ß3-deficient mice, exposure to oral dextran sodium sulfate induced lethality and severe inflammation in the small intestine. The lethality was due to PLC-ß3 deficiency in multiple non-hematopoietic cell types. PLC-ß3 deficiency resulted in reduced Wnt/ß-catenin signaling, which is essential for homeostasis and the regeneration of the intestinal epithelium. PLC-ß3 regulated the Wnt/ß-catenin pathway in small intestinal epithelial cells (IECs) at transcriptional, epigenetic, and, potentially, protein-protein interaction levels. PLC-ß3-deficient IECs were unable to respond to stimulation by R-spondin 1, an enhancer of Wnt/ß-catenin signaling. Reduced expression of PLC-ß3 and its signature genes was found in biopsies of patients with ileal Crohn's disease. PLC-ß regulation of Wnt signaling was evolutionally conserved in Drosophila. Our data indicate that a reduction in PLC-ß3-mediated Wnt/ß-catenin signaling contributes to the pathogenesis of ileal Crohn's disease.

m5C methylated lncRncr3-MeCP2 interaction restricts miR124a-initiated neurogenesis.

Coordination of neuronal differentiation with expansion of the neuroepithelial/neural progenitor cell (NEPC/NPC) pool is essential in early brain development. Our in vitro and in vivo studies identify independent and opposing roles for two neural-specific and differentially expressed non-coding RNAs derived from the same locus: the evolutionarily conserved lncRNA Rncr3 and the embedded microRNA miR124a-1. Rncr3 regulates NEPC/NPC proliferation and controls the biogenesis of miR124a, which determines neuronal differentiation. Rncr3 conserved exons 2/3 are cytosine methylated and bound by methyl-CpG binding protein MeCP2, which restricts expression of miR124a embedded in exon 4 to prevent premature neuronal differentiation, and to orchestrate proper brain growth. MeCP2 directly binds cytosine-methylated Rncr3 through previously unrecognized lysine residues and suppresses miR124a processing by recruiting PTBP1 to block access of DROSHA-DGCR8. Thus, miRNA processing is controlled by lncRNA m5C methylation along with the defined m5C epitranscriptomic RNA reader protein MeCP2 to coordinate brain development.

A panoptic segmentation dataset and deep-learning approach for explainable scoring of tumor-infiltrating lymphocytes.

Tumor-Infiltrating Lymphocytes (TILs) have strong prognostic and predictive value in breast cancer, but their visual assessment is subjective. To improve reproducibility, the International Immuno-oncology Working Group recently released recommendations for the computational assessment of TILs that build on visual scoring guidelines. However, existing resources do not adequately address these recommendations due to the lack of annotation datasets that enable joint, panoptic segmentation of tissue regions and cells. Moreover, existing deep-learning methods focus entirely on either tissue segmentation or cell nuclei detection, which complicates the process of TILs assessment by necessitating the use of multiple models and reconciling inconsistent predictions. We introduce PanopTILs, a region and cell-level annotation dataset containing 814,886 nuclei from 151 patients, openly accessible at: sites.google.com/view/panoptils . Using PanopTILs we developed MuTILs, a neural network optimized for assessing TILs in accordance with clinical recommendations. MuTILs is a concept bottleneck model designed to be interpretable and to encourage sensible predictions at multiple resolutions. Using a rigorous internal-external cross-validation procedure, MuTILs achieves an AUROC of 0.93 for lymphocyte detection and a DICE coefficient of 0.81 for tumor-associated stroma segmentation. Our computational score closely matched visual scores from 2 pathologists (Spearman R = 0.58-0.61, p < 0.001). Moreover, computational TILs scores had a higher prognostic value than visual scores, independent of TNM stage and patient age. In conclusion, we introduce a comprehensive open data resource and a modeling approach for detailed mapping of the breast tumor microenvironment.

Artificial Intelligence Can Be Regulated Using Current Patient Safety Procedures and Infrastructure in Hospitals.

This Viewpoint describes the potential benefits and harms of using artificial intelligence (AI) in health care decision-making processes.

Traumatic brain injury alters the effects of class II invariant peptide (CLIP) antagonism on chronic meningeal CLIP + B cells, neuropathology, and neurobehavioral impairment in 5xFAD mice.

BACKGROUND: Traumatic brain injury (TBI) is a significant risk factor for Alzheimer's disease (AD), and accumulating evidence supports a role for adaptive immune B and T cells in both TBI and AD pathogenesis. We previously identified B cell and major histocompatibility complex class II (MHCII)-associated invariant chain peptide (CLIP)-positive B cell expansion after TBI. We also showed that antagonizing CLIP binding to the antigen presenting groove of MHCII after TBI acutely reduced CLIP + splenic B cells and was neuroprotective. The current study investigated the chronic effects of antagonizing CLIP in the 5xFAD Alzheimer's mouse model, with and without TBI. METHODS: 12-week-old male wild type (WT) and 5xFAD mice were administered either CLIP antagonist peptide (CAP) or vehicle, once at 30 min after either sham or a lateral fluid percussion injury (FPI). Analyses included flow cytometric analysis of immune cells in dural meninges and spleen, histopathological analysis of the brain, magnetic resonance diffusion tensor imaging, cerebrovascular analysis, and assessment of motor and neurobehavioral function over the ensuing 6 months. RESULTS: 9-month-old 5xFAD mice had significantly more CLIP + B cells in the meninges compared to age-matched WT mice. A one-time treatment with CAP significantly reduced this population in 5xFAD mice. Importantly, CAP also improved some of the immune, histopathological, and neurobehavioral impairments in 5xFAD mice over the ensuing six months. Although FPI did not further elevate meningeal CLIP + B cells, it did negate the ability of CAP to reduce meningeal CLIP + B cells in the 5xFAD mice. FPI at 3 months of age exacerbated some aspects of AD pathology in 5xFAD mice, including further reducing hippocampal neurogenesis, increasing plaque deposition in CA3, altering microgliosis, and disrupting the cerebrovascular structure. CAP treatment after injury ameliorated some but not all of these FPI effects.

Blubber gene expression and cortisol concentrations reveal changing physiological stress in a Southern ocean sentinel species.

The health of migratory eastern Australian humpback whales (Megaptera novaeangliae) can reflect the condition of their remote polar foraging environments. This study used gene expression (LEP, LEPR, ADIQ, AhR, TNF-α, HSP-70), blubber hormone concentrations (cortisol, testosterone), and photogrammetric body condition to assess this sentinel species during a period of unprecedented changes to anthropogenic activity and natural processes. The results revealed higher cortisol concentrations in 2020 compared to 2021, suggesting a decline in physiological stress between years. Additionally, metabolic transcripts LEPR, and AhR, which is also linked to xenobiotic metabolism, were upregulated during the 2020 southbound migration. These differences suggest that one or more environmental stressors were reduced between 2020 and 2021, with upregulated AhR possibly indicating a Southern Ocean pollutant declined between the years. This research confirms a Southern Ocean-wide decrease in whale stress during the study period and informs efforts to identify key stressors on Antarctic marine ecosystems.