Parent Facilitation of Condom Access and HIV Testing Associated with Improved Sexual Health Outcomes for Sexual Minority Young Men.

Sexual minority young men experience a high HIV incidence. Parent-based interventions are promising for prevention efforts, but further research is needed to identify specific, replicable parental behaviors associated with improved sexual health outcomes for sexual minority young men. We assessed parental behaviors in the domains of facilitating access to condoms, providing instruction in condom use, and supporting HIV testing, and tested whether parental behaviors were associated with sons' condom use self-efficacy and intentions to get tested for HIV. Data came from the baseline assessment of a pilot trial of a parent-based HIV prevention program, and participants were dyads (n = 61) of sexual minority young men (M. age: 16.87; 46% racial/ethnic minority) and their parents (M. age: 44.31; 26% racial/ethnic minority). Parents and sons reported on parental behaviors in each domain. Results indicated that parents' facilitation of access to condoms was associated with sons' condom use self-efficacy, and parents' facilitation of HIV testing was associated with sons' HIV testing intentions. Findings were robust across both parent and son reports of parental behaviors. Parental condom use instruction was unrelated to sons' condom use self-efficacy. Findings suggest that parent-based HIV prevention programs for sexual minority young men should encourage parents to provide instrumental assistance to their sons in accessing condoms and HIV testing. There is a need for further research to identify underlying mechanisms.

The UTHealth Houston Adult Cardiovascular Genomics Certificate Program: Efficacy and Impact on Healthcare Professionals.

Background The demand for genetic services has outpaced the availability of resources, challenging clinicians untrained in genetic integration into clinical decision-making. The UTHealth Adult Cardiovascular Genomics Certificate (CGC) program trains non-genetic healthcare professionals to recognize, assess, and refer patients with heritable cardiovascular diseases. This asynchronous online course includes 24 modules in three tiers of increasing complexity, using realistic clinical scenarios, interactive dialogues, quizzes, and tests to reinforce learning. We hypothesized that the CGC will increase genomic competencies in this underserved audience and encourage applying genomic concepts in clinical practice. Methods Required course evaluations include pre- and post- assessments, knowledge checks in each module, and surveys for module-specific feedback. After 6 months, longitudinal feedback surveys gathered data on the long-term impact of the course on clinical practice and conducted focused interviews with learners. Results The CGC was accredited in September 2022. Principal learners were nurses (24%), nurse practitioners (21%), physicians (16%), and physician assistants. Scores of 283 learners in paired pre- and post-assessments increased specific skills related to recognizing heritable diseases, understanding inheritance patterns, and interpreting genetic tests. Interviews highlighted the CGC's modular structure and linked resources as key strengths. Learners endorsed confidence to use genetic information in clinical practice, such as discussing genetic concepts and risks with patients and referring patients for genetic testing. Learners were highly likely to recommend the CGC to colleagues, citing its role in enhancing heritable disease awareness. Conclusions The CGC program effectively empowers non-genetic clinicians to master genomic competencies, fostering collaboration to prevent deaths from heritable cardiovascular diseases, and potentially transforming healthcare education and clinical practice.

A force-sensitive mutation reveals a non-canonical role for dynein in anaphase progression.

The diverse roles of the dynein motor in shaping microtubule networks and cargo transport complicate in vivo analysis of its functions significantly. To address this issue, we have generated a series of missense mutations in Drosophila Dynein heavy chain. We show that mutations associated with human neurological disease cause a range of defects, including impaired cargo trafficking in neurons. We also describe a novel microtubule-binding domain mutation that specifically blocks the metaphase-anaphase transition during mitosis in the embryo. This effect is independent from dynein's canonical role in silencing the spindle assembly checkpoint. Optical trapping of purified dynein complexes reveals that this mutation only compromises motor performance under load, a finding rationalized by the results of all-atom molecular dynamics simulations. We propose that dynein has a novel function in anaphase progression that depends on it operating in a specific load regime. More broadly, our work illustrates how in vivo functions of motors can be dissected by manipulating their mechanical properties.

Altered extracellular matrix correlates with an immunosuppressive tumor microenvironment and disease progression in younger adults with oral cavity squamous cell carcinoma.

Introduction: Oral cavity squamous cell carcinoma (OSCC) occurs most frequently in patients >60 years old with a history of tobacco and alcohol use. Epidemiological studies describe increased incidence of OSCC in younger adults (<45 years). Despite its poor prognosis, knowledge of OSCC tumor microenvironment (TME) characteristics in younger adults is scarce and could help inform possible resistance to emerging treatment options. Methods: Patients with OSCC were evaluated using TCGA-HNSC (n=121) and a stage and subsite-matched institutional cohort (n=8) to identify differential gene expression focusing on the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT) processes in younger (≤45 years) vs. older adults (≥60 years). NanoString nCounter analysis was performed using isolated total RNA from formalin-fixed paraffin-embedded (FFPE) tumor samples. Stained tumor slides from young and old OSCC patients were evaluated for CD8+ T-cell counts using immunohistochemistry. Results: Younger OSCC patients demonstrated significantly increased expression of ECM remodeling and EMT process genes, as well as TME immunosuppression. Gene set enrichment analyses demonstrated increased ECM pathways and concurrent decreased immune pathways in young relative to old patients. Transcripts per million of genetic markers involved in ECM remodeling including LAMB3, VCAN, S100A9, COL5A1, and ITGB2 were significantly increased in tumors of younger vs. older patients (adjusted p-value < 0.10). Young patient TMEs demonstrated a 2.5-fold reduction in CD8+ T-cells as compared to older patients (p < 0.05). Conclusion: Differential gene expression impacting ECM remodeling and TME immunosuppression may contribute to disease progression in younger adult OSCC and has implications on response to evolving treatment modalities, such as immune checkpoint inhibitor therapy.

Effect of synthetic CT on dose-derived toxicity predictors for MR-only prostate radiotherapy.

Objectives: Toxicity-driven adaptive radiotherapy (RT) is enhanced by the superior soft tissue contrast of magnetic resonance (MR) imaging compared with conventional computed tomography (CT). However, in an MR-only RT pathway synthetic CTs (sCT) are required for dose calculation. This study evaluates 3 sCT approaches for accurate rectal toxicity prediction in prostate RT. Methods: Thirty-six patients had MR (T2-weighted acquisition optimized for anatomical delineation, and T1-Dixon) with same day standard-of-care planning CT for prostate RT. Multiple sCT were created per patient using bulk density (BD), tissue stratification (TS, from T1-Dixon) and deep-learning (DL) artificial intelligence (AI) (from T2-weighted) approaches for dose distribution calculation and creation of rectal dose volume histograms (DVH) and dose surface maps (DSM) to assess grade-2 (G2) rectal bleeding risk. Results: Maximum absolute errors using sCT for DVH-based G2 rectal bleeding risk (risk range 1.6% to 6.1%) were 0.6% (BD), 0.3% (TS) and 0.1% (DL). DSM-derived risk prediction errors followed a similar pattern. DL sCT has voxel-wise density generated from T2-weighted MR and improved accuracy for both risk-prediction methods. Conclusions: DL improves dosimetric and predicted risk calculation accuracy. Both TS and DL methods are clinically suitable for sCT generation in toxicity-guided RT, however, DL offers increased accuracy and offers efficiencies by removing the need for T1-Dixon MR. Advances in knowledge: This study demonstrates novel insights regarding the effect of sCT on predictive toxicity metrics, demonstrating clear accuracy improvement with increased sCT resolution. Accuracy of toxicity calculation in MR-only RT should be assessed for all treatment sites where dose to critical structures will guide adaptive-RT strategies. Clinical trial registration number: Patient data were taken from an ethically approved (UK Health Research Authority) clinical trial run at Guy's and St Thomas' NHS Foundation Trust. Study Name: MR-simulation in Radiotherapy for Prostate Cancer. ClinicalTrials.gov Identifier: NCT03238170.

Prediction of molecular subclasses of uveal melanoma by deep learning using routine haematoxylin-eosin-stained tissue slides.

AIMS: Uveal melanoma has a high propensity to metastasize. Prognosis is associated with specific driver mutations and copy number variations, and these can only be obtained after genetic testing. In this study we evaluated the efficacy of patient outcome prediction using deep learning on haematoxylin and eosin (HE)-stained primary uveal melanoma slides in comparison to molecular testing. METHODS: In this retrospective study of patients with uveal melanoma, 113 patients from the Erasmus Medical Centre who underwent enucleation had tumour tissue analysed for molecular classification between 1993 and 2020. Routine HE-stained slides were scanned to obtain whole-slide images (WSI). After annotation of regions of interest, tiles of 1024 × 1024 pixels were extracted at a magnification of 40×. An ablation study to select the best-performing deep-learning model was carried out using three state-of-the-art deep-learning models (EfficientNet, Vision Transformer, and Swin Transformer). RESULTS: Deep-learning models were subjected to a training cohort (n = 40), followed by a validation cohort (n = 20), and finally underwent a test cohort (n = 48). A k-fold cross-validation (k = 3) of validation and test cohorts (n = 113 of three classes: BAP1, SF3B1, EIF1AX) demonstrated Swin Transformer as the best-performing deep-learning model to predict molecular subclasses based on HE stains. The model achieved an accuracy of 0.83 ± 0.09 on the validation cohort and 0.75 ± 0.04 on the test cohort. Within the subclasses, this model correctly predicted 70% BAP1-mutated, 61% SF3B1-mutated and 80% EIF1AX-mutated UM in the test set. CONCLUSIONS: This study showcases the potential of the deep-learning methodology for predicting molecular subclasses in a multiclass manner using HE-stained WSI. This development holds promise for advanced prognostication of UM patients without the need of molecular or immunohistochemical testing. Additionally, this study suggests there are distinct histopathological features per subclass; mainly utilizing epithelioid cellular morphology for BAP1-classification, but an unknown feature distinguishes EIF1AX and SF3B1.

The role of revision sinus surgery in the initiation of dupilumab therapy: A real-world study of molecular and cellular features.

KEY POINTS: A persistent type 2 endotype signature exists in recalcitrant chronic rhinosinusitis with nasal polyps mucosa on dupilumab. Revision sinus surgery immediately prior to dupilumab reduces long-term interleukin (IL)-4/IL-13 tissue mRNA. Pre-dupilumab revision surgery is associated with reduced tissue eosinophils and GATA-3+ cells.

Cocoa and Polyphenol-Rich Cocoa Fractions Fail to Improve Acute Colonic Inflammation in Dextran Sulfate Sodium-Treated Mice.

SCOPE: A study is conducted to determine the anti-inflammatory effects of cocoa and polyphenol-rich cocoa fractions in the dextran sulfate sodium (DSS)-induced mouse model of acute colonic inflammation. METHODS AND RESULTS: Male C57BL/6J mice are treated with dietary cocoa powder, an extractable cocoa polyphenol fraction, or a non-extractable cocoa polyphenol fraction for 2 weeks prior to treatment with 2.5% DSS in the drinking water for 7 days to induce colonic inflammation. Cocoa treatment continues during the DSS period. Cocoa and/or cocoa fractions exacerbate DSS-induced weight loss and fail to mitigate DSS-induced colon shortening but do improve splenomegaly. Cocoa/cocoa fraction treatment fails to mitigate DSS-induced mRNA and protein markers of inflammation. Principal component analysis shows overlap between cocoa or cocoa fraction-treated mice and DSS-induced controls, but separation from mice not treated with DSS. CONCLUSION: The results suggest cocoa and cocoa polyphenols may not be useful in mitigating acute colonic inflammation.

Aeromonas dhakensis: A Zoonotic Bacterium of Increasing Importance in Aquaculture.

Aeromonas dhakensis is increasingly recognised to be an important pathogen responsible for disease losses in warm-water aquaculture and, similar to several other Aeromonas species, it can infect humans. Knowledge of A. dhakensis is accumulating, but this species remains relatively under-investigated compared to its close relative, Aeromonas hydrophila. The significance of A. dhakensis may have been overlooked in disease events of aquatic animals due to issues with reliable identification. Critical to appreciating the importance of this pathogen is the application of dependable molecular tools that enable accurate identification and discrimination from A. hydrophila and other motile aeromonads. This review aims to synthesise the key literature on A. dhakensis, particularly with relevance to aquaculture, including knowledge of the bacterium derived from disease case studies in aquatic hosts. Identification methods and strain phylogeny are discussed, with accurate detection important for prompt diagnosis and for distinguishing strains with heightened virulence. Increasing evidence suggests that A. dhakensis may be more virulent than A. hydrophila and correct identification is required to determine the zoonotic risks posed, which includes concerns for antibiotic-resistant strains. This review provides an impetus to improve species identification in the future and screen strain collections of presumptive Aeromonas spp. retrospectively to reveal the true prevalence and impact of A. dhakensis in aquaculture, the environment, and healthcare settings.

Designing eco-evolutionary experiments for restoration projects: Opportunities and constraints revealed during stickleback introductions.

Eco-evolutionary experiments are typically conducted in semi-unnatural controlled settings, such as mesocosms; yet inferences about how evolution and ecology interact in the real world would surely benefit from experiments in natural uncontrolled settings. Opportunities for such experiments are rare but do arise in the context of restoration ecology-where different "types" of a given species can be introduced into different "replicate" locations. Designing such experiments requires wrestling with consequential questions. (Q1) Which specific "types" of a focal species should be introduced to the restoration location? (Q2) How many sources of each type should be used-and should they be mixed together? (Q3) Which specific source populations should be used? (Q4) Which type(s) or population(s) should be introduced into which restoration sites? We recently grappled with these questions when designing an eco-evolutionary experiment with threespine stickleback (Gasterosteus aculeatus) introduced into nine small lakes and ponds on the Kenai Peninsula in Alaska that required restoration. After considering the options at length, we decided to use benthic versus limnetic ecotypes (Q1) to create a mixed group of colonists from four source populations of each ecotype (Q2), where ecotypes were identified based on trophic morphology (Q3), and were then introduced into nine restoration lakes scaled by lake size (Q4). We hope that outlining the alternatives and resulting choices will make the rationales clear for future studies leveraging our experiment, while also proving useful for investigators considering similar experiments in the future.

Las Bolitas Syndrome in Penaeus vannamei Hatcheries in Latin America.

In September 2023, several hatcheries in Latin America experienced significant mortality rates, up to 90%, in zoea stage 2 of Penaeus vannamei. Observations of fresh mounts revealed structures resembling lipid droplets, similar to those seen in a condition known as "las bolitas syndrome". Routine histopathological examinations identified detached cells and tissues in the digestive tracts of affected zoea, contrasting with the typical algal cell contents seen in healthy zoea. Polymerase chain reaction (PCR) testing for over 20 known shrimp pathogens indicated minimal differences between diseased and healthy batches. Both groups tested negative for acute hepatopancreatic necrosis disease (AHPND) but positive for Vibrio species and Rickettsia-like bacteria in the diseased samples. Histological analyses of the affected zoea revealed characteristic tissue degeneration in the hepatopancreas, forming spheres that eventually migrated into the upper gut, midgut, and midgut caeca, a pathology identified as bolitas syndrome (BS). Microbiological assessments revealed Vibrio species at concentrations of 106 CFU zoea/g in affected zoea, approximately two orders of magnitude higher than in healthy zoea. Bacterial isolation from both healthy and BS-affected zoea on thiosulphate-citrate-bile salts-sucrose (TCBS) agar and CHROMagar™ (Paris, France), followed by identification using API 20E, identified six strains of Vibrio alginolyticus. Despite similarities to "las bolitas syndrome" in fresh mounts, distinct histopathological differences were noted, particularly the presence of sloughed cells in the intestines and variations in hepatopancreatic lobes. This study highlights the critical need for further research to fully understand the etiology and pathology of bolitas syndrome in zoea stage 2 of P. vannamei to develop effective mitigation strategies for hatchery operations.

The Metabolic and Endocrine Effects of a 12-Week Allulose-Rich Diet.

The global rise in type 2 diabetes (T2D) and obesity necessitates innovative dietary interventions. This study investigates the effects of allulose, a rare sugar shown to reduce blood glucose, in a rat model of diet-induced obesity and T2D. Over 12 weeks, we hypothesized that allulose supplementation would improve body weight, insulin sensitivity, and glycemic control. Our results showed that allulose mitigated the adverse effects of high-fat, high-sugar diets, including reduced body weight gain and improved insulin resistance. The allulose group exhibited lower food consumption and increased levels of glucagon-like peptide-1 (GLP-1), enhancing glucose regulation and appetite control. Additionally, allulose prevented liver triglyceride accumulation and promoted mitochondrial uncoupling in adipose tissue. These findings suggest that allulose supplementation can improve metabolic health markers, making it a promising dietary component for managing obesity and T2D. Further research is needed to explore the long-term benefits and mechanisms of allulose in metabolic disease prevention and management. This study supports the potential of allulose as a safe and effective intervention for improving metabolic health in the context of dietary excess.

Clinical evaluation of AI-assisted muscle ultrasound for monitoring muscle wasting in ICU patients.

Muscle ultrasound has been shown to be a valid and safe imaging modality to assess muscle wasting in critically ill patients in the intensive care unit (ICU). This typically involves manual delineation to measure the rectus femoris cross-sectional area (RFCSA), which is a subjective, time-consuming, and laborious task that requires significant expertise. We aimed to develop and evaluate an AI tool that performs automated recognition and measurement of RFCSA to support non-expert operators in measurement of the RFCSA using muscle ultrasound. Twenty patients were recruited between Feb 2023 and July 2023 and were randomized sequentially to operators using AI (n = 10) or non-AI (n = 10). Muscle loss during ICU stay was similar for both methods: 26 ± 15% for AI and 23 ± 11% for the non-AI, respectively (p = 0.13). In total 59 ultrasound examinations were carried out (30 without AI and 29 with AI). When assisted by our AI tool, the operators showed less variability between measurements with higher intraclass correlation coefficients (ICCs 0.999 95% CI 0.998-0.999 vs. 0.982 95% CI 0.962-0.993) and lower Bland Altman limits of agreement (± 1.9% vs. ± 6.6%) compared to not using the AI tool. The time spent on scans reduced significantly from a median of 19.6 min (IQR 16.9-21.7) to 9.4 min (IQR 7.2-11.7) compared to when using the AI tool (p < 0.001). AI-assisted muscle ultrasound removes the need for manual tracing, increases reproducibility and saves time. This system may aid monitoring muscle size in ICU patients assisting rehabilitation programmes.

Trans-Activation of the Coactivator-Associated Arginine Methyltransferase 1 (Carm1) Gene by the Oncogene Product Tax of Human T-Cell Leukemia Virus Type 1.

Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma. The oncogene product Tax of HTLV-I is thought to play crucial roles in leukemogenesis by promoting proliferation of the virus-infected cells through activation of growth-promoting genes. These genes code for growth factors and their receptors, cytokines, cell adhesion molecules, growth signal transducers, transcription factors and cell cycle regulators. We show here that Tax activates the gene coding for coactivator-associated arginine methyltransferase 1 (CARM1), which epigenetically enhances gene expression through methylation of histones. Tax activated the Carm1 gene and increased protein expression, not only in human T-cell lines but also in normal peripheral blood lymphocytes (PHA-PBLs). Tax increased R17-methylated histone H3 on the target gene IL-2Rα, concomitant with increased expression of CARM1. Short hairpin RNA (shRNA)-mediated knockdown of CARM1 decreased Tax-mediated induction of IL-2Rα and Cyclin D2 gene expression, reduced E2F activation and inhibited cell cycle progression. Tax acted via response elements in intron 1 of the Carm1 gene, through the NF-κB pathway. These results suggest that Tax-mediated activation of the Carm1 gene contributes to leukemogenic target-gene expression and cell cycle progression, identifying the first epigenetic target gene for Tax-mediated trans-activation in cell growth promotion.

Impact of an oral nutritional supplement on the body composition of older adults with or at risk of malnutrition in an institutionalised setting: A randomised controlled trial.

BACKGROUND: Malnutrition often manifests as a body weight (BW) reduction and unhealthy alteration in body composition. The present study aimed to assess the efficacy of an oral nutritional supplement (ONS) in improving BW and body composition among older adults with malnutrition. METHODS: An open-label randomised controlled, parallel-group study was conducted among older adults (age ≥ 60 years) with/at risk of malnutrition (mini nutrition assessment-short form score ≤ 11). In total, 50 participants were randomly assigned to the intervention (IG) and control (CG) groups (1:1 ratio). The IG received the ONS (57 g/day; 247 kcal/serving, 12 g protein) before bedtime for 12 weeks. CG received 200 mL of water. Anthropometric measurements, body composition analysis, and dietary and physical activity assessments were performed at the beginning and end of the study. RESULTS: Forty-two participants (IG: 20, CG: 22) completed the study. The mean ± SD ages of the IG and CG were 75.4 ± 6.1 and 74.8 ± 5.2 years, respectively (p = 0.73). The IG had a significant increase in BW (+1.68 ± 1.16 vs. -0.46 ± 0.95 kg; p < 0.001), lean mass (+1.23 ± 0.93 vs. -0.45 ± 0.90 kg; p < 0.001) and fat mass (+0.54 ± 0.82 vs. -0.06 ± 0.82 kg; p = 0.02) compared to the CG. One-quarter of the IG (n = 5) achieved a weight gain > 5% of BW, whereas none in the CG did (p = 0.01). No significant changes were observed in bone mineral content in either group. CONCLUSIONS: For malnourished older adults, supplementing with an ONS, along with regular food intake, significantly increased BW, lean mass and fat mass compared to control following the regular diet without supplementation.

Shunt-mediated decompression sickness in a compressed air worker with an atrial septal defect.

We report a compressed air worker who had diffuse cutaneous decompression sickness with pain in his left shoulder and visual disturbance characteristic of migraine aura after only his third hyperbaric exposure. The maximum pressure was 253 kPa gauge with oxygen decompression using the Swanscombe Oxygen Decompression Table. He was found to have a very large right-to-left shunt across a 9 mm atrial septal defect. He had transcatheter closure of the defect but had some residual shunting with release of a Valsalva manoeuvre. Thirty-two other tunnel workers undertook the same pressure profile and activities in the same working conditions during the maintenance of a tunnel boring machine for a total of 233 similar exposures and were unaffected. As far as we are aware this is the first report of shunt-mediated decompression sickness in a hyperbaric tunnel worker in the United Kingdom and the second case reported worldwide. These cases suggest that shunt-mediated decompression sickness should be considered to be an occupational risk in modern compressed air working. A right-to-left shunt in a compressed air worker should be managed in accordance with established clinical guidance for divers.

Discovery of RXFP2 genetic association in resistant hypertensive men and RXFP2 antagonists for the treatment of resistant hypertension.

Hypertension remains a leading cause of cardiovascular and kidney diseases. Failure to control blood pressure with ≥ 3 medications or control requiring ≥ 4 medications is classified as resistant hypertension (rHTN) and new therapies are needed to reduce the resulting increased risk of morbidity and mortality. Here, we report genetic evidence that relaxin family peptide receptor 2 (RXFP2) is associated with rHTN in men, but not in women. This study shows that adrenal gland gene expression of RXFP2 is increased in men with hypertension and the RXFP2 natural ligand, INSL3, increases adrenal steroidogenesis and corticosteroid secretion in human adrenal cells. To address the hypothesis that RXFP2 activation is an important mechanism in rHTN, we discovered and characterized small molecule and monoclonal antibody (mAb) blockers of RXFP2. The novel chemical entities and mAbs show potent, selective inhibition of RXFP2 and reduce aldosterone and cortisol synthesis and release. The RXFP2 mAbs have suitable rat pharmacokinetic profiles to evaluate the role of RXFP2 in the development and maintenance of rHTN. Overall, we identified RXFP2 activity as a potential new mechanism in rHTN and discovered RXFP2 antagonists for the future interrogation of RXFP2 in cardiovascular and renal diseases.

How schema knowledge influences memory in older adults: Filling in the gaps, or leading memory astray?

Age-related declines in episodic memory do not affect all types of mnemonic information equally: when to-be-remembered information is in line with one's prior knowledge, or schema-congruent, older adults often show no impairments. There are two major accounts of this effect: One proposes that schemas compensate for memory failures in aging, and the other proposes that schemas instead actively impair older adults' otherwise intact memory for incongruent information. However, the evidence thus far is inconclusive, likely due to methodological constraints in teasing apart these complex underlying dynamics. We developed a paradigm that separately examines the contributions of underlying memory and schema knowledge to a final memory decision, allowing these dynamics to be examined directly. In the present study, healthy older and younger adults first searched for target objects in congruent or incongruent locations within scenes. In a subsequent test, participants indicated where in each scene the target had been located previously, and provided confidence-based recognition memory judgments that indexed underlying memory, in terms of recollection and familiarity, for the background scenes. We found that age-related increases in schema effects on target location spatial recall were predicted and statistically mediated by age-related increases in underlying memory failures, specifically within recollection. We also found that, relative to younger adults, older adults had poorer spatial memory precision within recollected scenes but slightly better precision within familiar scenes-and age increases in schema bias were primarily exhibited within recollected scenes. Interestingly, however, there were also slight age-related increases in schema effects that could not be explained by memory deficits alone, outlining a role for active schema influences as well. Together, these findings support the account that age-related schema effects on memory are compensatory in that they are driven primarily by underlying memory failures, and further suggest that age-related deficits in memory precision may also drive schema effects.