Age-related Changes Research Articles

Developmental patterns of inhibition and fronto-basal-ganglia white matter organisation in healthy children and children with attention-deficit/hyperactivity disorder.

There is robust evidence implicating inhibitory deficits as a fundamental behavioural phenotype in children with attention-deficit/hyperactivity disorder (ADHD). However, prior studies have not directly investigated the role in which white matter properties within the fronto-basal-ganglia circuit may play in the development of inhibitory control deficits in this group. Combining recent advancements in brain-behavioural modelling, we mapped the development of stop-signal task (SST) performance and fronto-basal-ganglia maturation in a longitudinal sample of children aged 9-14 with and without ADHD. In a large sample of 135 ADHD and 138 non-ADHD children, we found that the ADHD group had poorer inhibitory control (i.e., longer stop-signal reaction times) across age compared to non-ADHD controls. When applying the novel parametric race model, this group effect was driven by higher within-subject variability (sigma) and higher number of extreme responses (tau) on stop trials. The ADHD group also displayed higher within-subject variability on correct responses to go stimuli. Moreover, we observed the ADHD group committing more task-based failures such as responding on stop trials (trigger failures) and omissions on go trials (go failures) compared to non-ADHD controls, suggesting the contribution of attentional lapses to poorer response inhibition performance. In contrast, longitudinal modelling of fixel-based analysis measures revealed no significant group differences in the maturation of fronto-basal-ganglia fibre cross-section in a subsample (74 ADHD and 73 non-ADHD children). Finally, brain-behavioural models revealed that age-related changes in fronto-basal-ganglia morphology (fibre cross-section) were significantly associated with reductions in the variability of the correct go-trial responses (sigma.true) and skew of the stop-trial distribution (tauS). However, this effect did not differ between ADHD and typically developing children. Overall, our findings support the growing consensus suggesting that attentional deficits subserve ADHD-related inhibitory dysfunction. Furthermore, we show novel evidence suggesting that while children with ADHD are consistently performing worse on the SST than their non-affected peers, they appear to have comparable rates of neurocognitive maturation across this period.

Elicitation tasks, language contact, and syllable structure in Budai Rukai

Abstract This target paper builds on previous literature in Budai Rukai to develop a nuanced framework for examining the syllable structure and the impact of Chinese language education on speakers’ judgments. It demonstrates new dimensions of overarching corroboration of intonational phonology and is a worthwhile endeavor. In this commentary, I address the issues of elicitation tasks and language contact by illustrating that the syllable structure of Budai Rukai is still undergoing age-related changes and remains to be discussed.

A Whole-Brain Model of the Aging Brain During Slow Wave Sleep.

Age-related brain changes affect sleep and are reflected in properties of sleep slow-waves, however, the precise mechanisms behind these changes are still not completely understood. Here, we adapt a previously established whole-brain model relating structural connectivity changes to resting state dynamics, and extend it to a slow-wave sleep brain state. In particular, starting from a representative connectome at the beginning of the aging trajectory, we have gradually reduced the inter-hemispheric connections, and simulated sleep-like slow-wave activity. We show that the main empirically observed trends, namely a decrease in duration and increase in variability of the slow waves are captured by the model. Furthermore, comparing the simulated EEG activity to the source signals, we suggest that the empirically observed decrease in amplitude of the slow waves is caused by the decrease in synchrony between brain regions.

Is neck pain a marker for something serious? Like myelopathy.

Degenerative Cervical Myelopathy (DCM) is a chronic progressive condition of the cervical spine that leads to compression of the spinal cord. It is the most common cause of spinal cord dysfunction in adults, and it occurs due to age-related changes or genetically associated pathologies. DCM is a clinical and radiological diagnosis and presents with a spectrum of symptoms ranging from neck pain and stiffness to paralysis. While neck pain is prevalent amongst patients attending specialist clinics, its predictive value for DCM is limited. This paper focuses on elucidating the relationship between DCM and chronic neck pain, and we discuss the underlying aetiology and broader neurological implications in the context of the literature. The progression of DCM can be slow and insidious with symptoms worsening gradually over time. Neck pain should not be discounted in the evaluation of DCM.

Age and gender related changes on total antioxidant/oxidant status and electrolyte composition of saliva

BackgroundSaliva is used as an important biological material in the diagnosis and treatment of various diseases to collect easily, to be cheap, to have a minimal risk of infection. Here in that study we aimed to evaluate age and gender-related changes on total antioxidant/oxidant status and electrolyte composition of saliva levels in individuals. MethodsA total of 30 young adult (21.2 ± 2.47 years) and 14 adult (51.6 ± 9.35 years) subjects were included in the study. Stimulated saliva samples were collected. Cortisol, amylase, oxidative stress biomarkers (total antioxidant status and total oxidant status) were measured by ELISA and spectrophotometric manual methods and electrolyte level of saliva samples were determined by autoanalyzer. ResultsSalivary concentrations of biomarkers of young adults were compared to adult subjects, there was a statistically significant difference between cortisol (μg/dL) (p = 0.003), Ca+2(mg/dL) (p = 0.004), TAS (mmol Trolox Equiv/L) (p = 0.001), BUN (mg/dL) (p = 0.02), Mg+2 (mg/dL) (p = 0.02), and K+ (mmol/L) (p = 0.05) levels, but there was no significant difference was found between uric acid (mg/dL) (p = 0.44), Cl- (mmol/L) (p = 0.07), amylase (ng/mL) (p = 0.47), phosphate (mg/dL) (p = 0.63), Na+(mmol/L)(p = 0.21), and TOS (μmol H2O2 Equiv/L) (p = 0.70) levels. We evaluated salivary cortisol, amylase, and electrolyte levels of groups that we commented on their relationship between oxidant-antioxidant defense systems of the saliva and their correlations with age and gender. ConclusionsThis study could suggest the use of saliva samples to correlate with age and representing the levels of the most common biological parameters for routine use and antioxidant-oxidant enzymes for clinical trials.

Age-Related Changes in Heart Rate Variability from the Neonatal Period to Adulthood.

The aim of the study was to reveal the patterns of the age-related dynamics of the frequency-dependent regulation of heart rate variability (HRV) based on the analysis of Holter ECG recordings from healthy subjects of four age groups: neonates, one-year-old infants, adolescents, and adults. A wide spectral composition of HRV is shown, consisting of nine Hilbert-Huang modes in the frequency range from 0.0001 to 2 Hz. A decrease in the central frequencies of all modes is shown in the postnatal period with a plateau in adolescence. A rapid progression of systemic humoral regulation of HRV, characterized by a consolidated increase in the amplitudes of the corresponding modes with a plateau in adolescence, is demonstrated. The dome-shaped character of age-related changes in amplitude of modes associated with autonomic control with a maximum in adolescence is shown. The results obtained quantitatively demonstrate age-related consolidated changes in HRV parameters from neonates to adulthood.

Constitutive Pleiotrophin Deletion Results in a Phenotype with an Altered Pancreatic Morphology and Function in Old Mice.

Pleiotrophin (PTN) is crucial for embryonic development and pancreas organogenesis as it regulates metainflammation, metabolic homeostasis, thermogenesis, and glucose tolerance. Pleiotrophin deletion is associated with a lipodystrophic phenotype in which adipose tissue plasticity is altered in late life. This study explored the impact of pleiotrophin deletion on pancreatic morphology and function in later life. We analyzed glucose tolerance and circulating parameters on female wild-type (Ptn+/+) and knock-out (Ptn-/-) mice. At 9 and 15 months, we conducted morphometric analyses of pancreatic islets and evaluated the levels of insulin, glucagon, somatostatin, glucose transporter 2 (GLUT2), vesicle-associated membrane protein 2 (VAMP2), and synaptosome-associated protein 25 (SNAP25) via immunofluorescence. The effect of PTN on glucose-stimulated insulin secretion (GSIS) was evaluated in INS1E cells and isolated islets. Ptn-/- mice showed hyperinsulinemia, impaired glucose tolerance, and increased homeostatic model assessment for insulin resistance (HOMA-IR) with age. While Ptn+/+ islets enlarge with age, in Ptn-/- mice, the median size decreased, and insulin content increased. Vesicle transport and exocytosis proteins were significantly increased in 9-month-old Ptn-/- islets. Islets from Ptn-/- mice showed impaired GSIS and decreased cell membrane localization of GLUT2 whereas, PTN increased GSIS in INS1E cells. Ptn deletion accelerated age-related changes in the endocrine pancreas, affecting islet number and size, and altering VAMP2 and SNAP25 levels and GLUT2 localization leading to impaired GSIS and insulin accumulation in islets.

Sirtuin 3 drives sex-specific responses to age-related changes in mouse embryonic fibroblasts

The aging process is a complex phenomenon characterised by a gradual decline in physiological functions and an increased susceptibility to age-related diseases. An important factor in aging is mitochondrial dysfunction, which leads to an accumulation of cellular damage over time. Mitochondrial Sirtuin 3 (Sirt3), an important regulator of energy metabolism, plays a central role in maintaining mitochondrial function. Loss of Sirt3 can lead to reduced energy levels and an impaired ability to repair cellular damage, a hallmark of the aging process. In this study we investigated the impact of Sirt3 loss on mitochondrial function, metabolic responses and cellular aging processes in male and female mouse embryonic fibroblasts (MEF) exposed to etoposide-induced DNA damage, which is commonly associated with cellular dysfunction and senescence. We found that Sirt3 contributes to the sex-specific metabolic response to etoposide treatment. While male MEF exhibited minimal damage suggesting potential prior adaptation to stress due to Sirt3 loss, female MEF lacking Sirt3 experienced higher vulnerability to genotoxic stress, implying a pivotal role of Sirt3 in their resistance to such challenges. These findings offer potential insights into therapeutic strategies targeting Sirt3- and sex-specific signalling pathways in diseases associated with DNA damage that play a critical role in the aging process.

Stress fracture of bone under physiological multiaxial cyclic loading: Activity-based predictive models

While it is known that excessive accumulation of fatigue damage from daily activities contributes to fracture, a model of bone failure under physiologically relevant multiaxial cyclic loading needs to be developed in order to develop effective management strategies for stress or fatigue fractures. The role of strain-induced damage from repetitive loading is a strong candidate for such a model, as cycles of mechanical loading leading to failure can be measured directly. However, this approach has been limited by the restrictions of uniaxial loading models, which often overestimates the fatigue life of bone and suggests that bone will only break well beyond the realistic limits of exercise. To address this gap and develop a physiologically relevant model, our study leverages the power of four commonly used engineering failure criteria as a model for multiaxial loading using a cohort of human tibiae from cadaveric donors (age range 21–85 years old). Four failure criteria (Von Mises, Tsai-Wu, Findley critical plane, and maximum shear strain) were found to be effective in vitro models of tibial fracture when age groups of donors were combined (r2 > 0.84) and stratified (younger: 21–52-years-old versus older: 57–85-years-old) (r2 > 0.83) (p < 0.001). Each failure criterion displayed distinctly lower fatigue curves for the older age group. The maximum shear strain model was used to determine the efficacy of this approach to predict fatigue fractures in humans using published in vivo data from human volunteers. Consistent with in vivo observations in general population, the model demonstrated failure at 5000 to 200,000 loading cycles depending on activities such as jumping, sprinting, and walking, with a 3-fold reduction of fatigue life in older donors. These findings dramatically improve estimates of fatigue life under repetitive loading and demonstrate how age-related changes in bone significantly increase its propensity for fatigue-induced fractures.

Natural variation in age-related dopamine neuron degeneration is glutathione dependent and linked to life span

Aging is the biggest risk factor for Parkinson's disease (PD), suggesting that age-related changes in the brain promote dopamine neuron vulnerability. It is unclear, however, whether aging alone is sufficient to cause significant dopamine neuron loss, and if so, how this intersects with PD-related neurodegeneration. Here, through examining a large collection of naturally varying Drosophila strains, we find a strong relationship between life span and age-related dopamine neuron loss. Strains with naturally short-lived animals exhibit a loss of dopamine neurons without generalized neurodegeneration, while animals from long-lived strains retain dopamine neurons across age. Metabolomic profiling reveals lower glutathione levels in short-lived strains which is associated with elevated levels of reactive oxygen species (ROS), sensitivity to oxidative stress, and vulnerability to silencing the familial PD gene parkin. Strikingly, boosting neuronal glutathione levels via glutamate-cysteine ligase (Gcl) overexpression is sufficient to normalize ROS levels, extend life span, and block dopamine neurons loss in short-lived backgrounds, demonstrating that glutathione deficiencies are central to neurodegenerative phenotypes associated with short longevity. These findings may be relevant to human PD pathogenesis, where glutathione depletion is reported to occur in the idiopathic PD patient brain through unknown mechanisms. Building on this, we find reduced expression of the Gcl catalytic subunit in both Drosophila strains vulnerable to age-related dopamine neuron loss and in the human brain from familial PD patients harboring the common LRRK2 G2019S mutation. Our study across Drosophila and human PD systems suggests that glutathione synthesis and levels play a conserved role in regulating age-related dopamine neuron health.

Study of age-related retinal hemodynamic changes by laser speckle flowgraphy

Background: Diagnostics of hemodynamic changes is important both for clarifying the features of the course of pathological process of many ophthalmic diseases and for optimizing treatment tactics. Laser speckle flowgraphy (LSFG) is a new non-invasive method for quantitative assessment of retinal blood flow. Aim: To study age-related changes of pulse waves both in large blood vessels and microvasculature in the optic nerve head and macula by laser speckle flowgraphy. Materials and methods: Age-related changes in blood flow were studied in 60 healthy volunteers using LSFG-RetFlow. We analyzed MBR — main parameter of pulse wave assessed by the laser speckle flowgraphy and also another 8 pulse wave parameters for large vessels and microvasculature in the areas of optic nerve head and macula. Results: The study revealed statistically significant (p ≤ 0.05) age-related changes in pulse waves for most parameters under study. In the large vessels of the optic disc blood flow dropped after 60 years, while in the microvasculature it decreased progradiently in the groups older than 40 and 60 years. In the macular region, blood flow in large vessels and microvasculature decreased mainly in the group aged over 61. Age-related changes in pulse wave parameters were unidirectional for both large vessels and microvasculature; trends were similar in both areas under investigation. Conclusions: The study demonstrated statistically significant (age-related changes in most laser speckle flowgraphy pulse wave parameters. The MBR, MV (MBR of Vascular area), MT (MBR of Tissue area) indicators are most informative in the ophthalmic hemodinamic screening. The study of another pulse wave parameters seems sufficient for the general MBR.

Decoding Brain Development and Aging

Abstract The aging process induces a variety of changes in the brain detectable by magnetic resonance imaging (MRI). These changes include alterations in brain volume, fluid-attenuated inversion recovery (FLAIR) white matter hyperintense lesions, and variations in tissue properties such as relaxivity, myelin, iron content, neurite density, and other microstructures. Each MRI technique offers unique insights into the structural and compositional changes occurring in the brain due to normal aging or neurodegenerative diseases. Age-related brain volume changes encompass a decrease in gray matter and an increase in ventricular volume, associated with cognitive decline. White matter hyperintensities, detected by FLAIR, are common and linked to cognitive impairments and increased risk of stroke and dementia. Tissue relaxometry reveals age-related changes in relaxivity, aiding the distinction between normal aging and pathological conditions. Myelin content, measurable by MRI, changes with age and is associated with cognitive and motor function alterations. Iron accumulation, detected by susceptibility-sensitive MRI, increases in certain brain regions with age, potentially contributing to neurodegenerative processes. Diffusion MRI provides detailed insights into microstructural changes such as neurite density and orientation. Neurofluid imaging, using techniques like gadolinium-based contrast agents and diffusion MRI, reveals age-related changes in cerebrospinal and interstitial fluid dynamics, crucial for brain health and waste clearance. This review offers a comprehensive overview of age-related brain changes revealed by various MRI techniques. Understanding these changes helps differentiate between normal aging and pathological conditions, aiding the development of interventions to mitigate age-related cognitive decline and other symptoms. Recent advances in machine learning and artificial intelligence have enabled novel methods for estimating brain age, offering also potential biomarkers for neurological and psychiatric disorders.

Age-related changes in carcass composition, physicochemical properties, texture and microstructure of meat from White King pigeons

ABSTRACT 1. An experiment was conducted to explore the age-related changes in carcass composition, physicochemical properties, texture and microstructure of meat from White King pigeons. The study used 32 carcasses collected from White King pigeons (16 aged 4 weeks and 16 aged 180 weeks). 2. The 180-week-old White King pigeons had a higher percentage of eviscerated carcass characteristics. The 4-week-old pigeons were characterised by higher percentage of skin with subcutaneous fat and carcass remainders. There were significant differences in chemical and physicochemical characteristics as well as in texture and microstructure parameters amongst White King pigeons of different ages. 3. In conclusion, the study demonstrated that the age of White King pigeons has a considerable impact on carcass composition, physicochemical properties, meat texture and microstructure. Older pigeons had higher percentages of eviscerated carcass components, which may reflect maturation, while younger pigeons had greater proportions of fat and carcass remainders. These findings suggest that age-related changes should be considered when evaluating meat quality and composition, as each age group presented distinct characteristics.

Elderly age and tuberculosis: diagnostics difficulties and course features

ABSTRACT. The clinical observation of an elderly female patient, who was being treated at the Zaporizhzhia Regional Phthisiopulmonology Clinical Treatment and Diagnostic Center, is presented, the features of the diagnostics and the course of the tuberculosis process is determined. The clinical case demonstrates the difficulty of timely tuberculosis diagnostics due to numerous comorbidities in an elderly woman. Most cases of tuberculosis in the elderly are associated with the reactivation of old specific foci, which can be explained by age-related changes in the immune system. In this case, the difficulty of the timely tuberculosis diagnostics was associated with non-specific symptoms of the active process and the absence of bacterial excretion 2 years ago in an elderly woman. As a result, a diagnosis of malignant neoplasm of the upper lobe of the left lung was mistakenly made. The outcomes of the disease led to the development of fibrocavernous tuberculosis with multidrug resistance. The woman had a good adherence to the treatment, which gave a positive result.

Single-cell analysis reveals alternations between the aged and young mice prostates

BackgroundAging of the male prostate is an inevitable process in which the prostate undergoes hyperplasia, and this growth may lead to compression of the urethra, resulting in voiding dysfunction and associated symptoms, and an increased risk of prostate cancer. Despite the significance of prostate aging, the molecular mechanisms involved are still not fully understood.MethodsProstate split by lobes from young (2 months) and aged (24 months) mice were collected for single-cell RNA sequencing (scRNA-seq) analysis. Tissues from both anterior prostate (AP) and ventral/dorsal/lateral prostate (VDLP) were included in the study. Data analysis included unsupervised clustering using the uniform manifold approximation and projection (UMAP) algorithm to identify distinct cell types based on marker gene expression. Differential gene expression analysis was performed to identify age-related changes in gene expression across different cell types. Functional enrichment analysis was conducted to elucidate biological pathways associated with differentially expressed genes. Additionally, cellular interactions and developmental trajectories were analyzed to characterize cellular dynamics during prostate aging.ResultsThe single-cell transcriptome analysis of the mouse prostate during aging revealed heterogeneity across various cell types and their changes during the aging process. We found a significant increase in the proportion of mesenchymal and immune cells in aged mice. Our study unveiled alterations in genes and pathways associated with cellular senescence, oxidative stress, and regeneration in epithelial cells. Furthermore, we observed that basal cells may undergo epithelial-mesenchymal transition (EMT) to become mesenchymal cells, particularly prominent in aged mice. Additionally, immune cells, notably macrophages and T cells, exhibited a heightened inflammatory response in aged mice.ConclusionIn summary, our study provides a comparative analysis of the single-cell transcriptome of the aged and young mice prostates, elucidating cellular and molecular changes between the aged and young mice prostates.

Evaluation of the effect of CYP2D6 and OCT1 polymorphisms on the pharmacokinetics of tramadol: Implications for clinical safety and dose rationale in paediatric chronic pain.

Our investigation aimed to assess the dose rationale of tramadol in paediatric patients considering the effect of CYP2D6/OCT1 polymorphisms on systemic exposure. Recommendations were made for the oral dose of tramadol to be used in a prospective study in children (3months to < 18 years old) with chronic pain. Intravenous pharmacokinetic and genotype data from neonatal patients (n = 46) were available for this analysis. The time course of tramadol and O-desmethyltramadol (M1) concentrations was characterized using a nonlinear mixed effects approach in conjunction with extrapolation principles. Clinical trial simulations were then implemented to explore the effects of polymorphism, maturation and developmental growth on the disposition of tramadol and M1. Reported efficacious exposure range in adult subjects were used as reference. The pharmacokinetics of tramadol and M1 was characterized by a two-compartment model. The total clearance of tramadol (CLPP) comprised CYP2D6-mediated metabolism (CLPM) and other pathways (CLPO). Age-related changes in CLPM, CLPO and M1 clearance (CLMO) were described by a sigmoid function, with CYP2D6 as a covariate on CLPP and CLPM, and OCT1 on CLMO. Simulation scenarios includingdifferent CYP2D6/OCT1 combinations revealed that steady-state concentrations are above the putative ranges for analgesia in >15% and >70% of subjects after doses of 3 and 8mg/kg, respectively. In the absence of genotyping, reference exposure ranges can be used to define the dose rationale for tramadol in paediatric chronic pain. However, a starting dose of 0.5mg/kg/day should be considered, followed by stepwise titration to the desired analgesic response.

Diagnostic value of effusion adenosine deaminase, γ-interferon release assay and effusion lactatedehy drogenase/effusion adenosine deaminase for tuberculous pleural effusion in patients aged 60 years and above.

China is experiencing rapid growth in its population of older adults, which may lead to increased susceptibility to tuberculous pleural effusion (TPE) due to age-related changes in the immune system. This study aimed to investigate the diagnostic potential of multiple biomarkers in individuals aged 60 years and above with pleural effusion. A total of 519 adult patients from Ningbo First Hospital were included in the study, with 7 biomarkers and their ratios in serum and pleural effusion analyzed using logistic regression analysis. Effusion Adenosine Deaminase(ADA), γ-Interferon Release Assay(IGRA), and Effusion lactatedehy drogenase(LDH)/Effusion ADA were identified as valuable parameters for differentiating TPE from non-TPE, particularly in individuals aged 60 years and older. Effusion ADA, IGRA, and Effusion LDH/Effusion ADA were identified as valuable parameters for the differential diagnosis of TPE from non-TPE, showing good diagnostic performance in individuals aged 60 years and older. The combined diagnosis of these three indexes achieved the highest diagnostic accuracy for TPE in this age group, with an AUC of 0.925, sensitivity of 85.23%, and specificity of 89.57%. Overall, the study highlights the importance of using multiple indicators for a combined diagnosis to improve diagnostic efficacy in detecting tuberculous pleurisy in older individuals as for young patients.

Knockout of &lt;i&gt;Hsp70&lt;/i&gt; genes modulates age-related transcriptomic changes in leg muscles, reduces locomotion speed and lifespan of &lt;i&gt;Drosophila melanogaster&lt;/i&gt;

The study investigated the effect of knockout of six Hsp70 genes (orthologues of the mammalian genes Hspa1a, Hspa1b, Hspa2 and Hspa8) on age-related changes in gene expression in the legs of Drosophila melanogaster, which contain predominantly skeletal muscle bundles. For this, the leg transcriptomic profile was examined in males of the w1118 control line and the Hsp70– line on the 7th, 23rd and 47th days of life. In w1118 flies, an age-related decrease in the locomotion (climbing) speed (a marker of functional state and endurance) was accompanied by a pronounced change in the transcriptomic profile of the leg skeletal muscles, which is conservative in nature. In Hsp70– flies, the median lifespan was shorter and the locomotion speed was significantly lower compare to the control; at the same time, complex changes in the age-related dynamics of the skeletal muscle transcriptome were observed. Mass spectrometry-based quantitative proteomic showed that 47-day-old Hsp70– flies, compared with w1118, demonstrated multidirectional changes in the content of key enzymes of glucose metabolism and fat oxidation (glycolysis, pentose phosphate pathway, Krebs cycle, beta-oxidation and oxidative phosphorylation). Such dysregulation may be associated with a compensatory increase in the expression of other genes encoding chaperones (small Hsp, Hsp40, 60, and 70), which regulate specific sets of target proteins. Taken together, our data show that knockout of six Hsp70 genes slightly reduces the median lifespan of flies, but significantly reduces the locomotion speed, which may be associated with complex changes in the transcriptome of the leg skeletal muscles and with multidirectional changes in the content of key enzymes of energy metabolism.

Pitfalls in Interpretive Applications of Artificial Intelligence in Radiology.

Interpretive artificial intelligence (AI) tools are poised to change the future of radiology. However, certain pitfalls may pose particular challenges for optimal AI interpretative performance. These include anatomic variants, age-related changes, postoperative changes, medical devices, image artifacts, lack of integration of prior and concurrent imaging examinations and clinical information, and the satisfaction-of-search effect. Model training and development should account for such pitfalls to minimize errors and optimize interpretation accuracy. More broadly, AI algorithms should be exposed to diverse and complex training datasets to yield a holistic interpretation that considers all relevant information beyond the individual examination. Successful clinical deployment of AI tools will require that radiologist end users recognize these pitfalls and other limitations of the available models. Furthermore, developers should incorporate explainable AI techniques (e.g., heat maps) into their tools, to improve radiologists' understanding of model outputs and to enable radiologists to provide feedback for guiding continuous learning and iterative refinement. In this article, we provide an overview of common pitfalls that radiologists may encounter when using interpretive AI products in daily practice. We present how such pitfalls lead to AI errors and offer potential strategies that AI developers may use for their mitigation.

Attenuated melanopsin-mediated post-illumination pupillary response (PIPR) is associated with reduced actigraphic amplitude and mesor in older adults.

This study aimed to explore the relationship between post-illumination pupillary response (PIPR) with sleep and circadian measures in a community sample of healthy older adults. Eligible participants were invited to complete a one-week sleep diary, actigraphy and provide an overnight urine sample to measure urinary 6-sulfatoxymelatonin (aMT6s). PIPR was defined as the as the pupil constriction at 6s post-stimulus (PIPR-6s), and ii) for 30s beginning 10s after stimulus (PIPR-30s) normalized as a percentage to the baseline pupil diameter, after 1s of blue and 1s of red-light stimulus, respectively. The Net-PIPRs were reported by subtracting the PIPR to red stimulus from the PIPR to blue stimulus. The relationship between PIPR metrics to aMT6s and actigraphic rest-activity rhythm parameters was examined by generalized linear models. A total of 48 participants were recruited (Mean age: 62.6 ± 7.1 years, Male: 44%). Both Net PIPR-6s and Net PIPR-30s were significantly associated with actigraphic rest-activity amplitude (B=0.03, p=0.001 and B=0.03, p=0.01, respectively), and actigraphic rest-activity mesor (B=0.02, p=0.001 and B=0.03, p=0.004, respectively). Additionally, the Net PIPR-30s were positively associated with overnight aMT6s level (B=0.04, p=0.03), and negatively associated with actigraphic rest-activity acrophase (B=-0.01, p=0.004) in the fully adjusted models. Attenuated PIPR is associated with a reduced actigraphic amplitude and mesor. The reduced retinal light responsivity may be a potential pathway contributing to impaired photic input to the circadian clock and resulted in the age-related circadian changes in older adults.