A novel grading approach predicts worse outcomes in stage pT1 non-muscle-invasive bladder cancer.

OBJECTIVE: To develop a prognostically relevant scoring system for stage pT1 non-muscle-invasive bladder cancer (NMIBC) incorporating tumour budding, growth pattern and invasion pattern because the World Health Organisation grading system shows limited prognostic value in such patients. PATIENTS AND METHODS: The tissue specimens and clinical data of 113 patients with stage pT1 NMIBC who underwent transurethral resection of bladder tumour were retrospectively investigated. Tumour budding, and growth and invasion patterns were evaluated and categorised into two grade groups (GGs). GGs and other clinical and histopathological variables were investigated regarding recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS) using univariable and multivariable Cox regression analyses. RESULTS: The integration of two tumour budding groups, two growth patterns, and two invasion patterns yielded an unfavourable GG (n = 28; 24.7%) that had a high impact on oncological outcomes. The unfavourable GG was identified as an independent RFS and OS predictor (P = 0.004 and P = 0.046, respectively) and linked to worse PFS (P = 0.001) and CSS (P = 0.001), irrespective of the European Association of Urology risk group. The unfavourable GG was associated with higher rates of BCG-unresponsive tumours (P = 0.006). Study limitations include the retrospective, single-centre design, diverse therapies and small cohort. CONCLUSIONS: We present a morphology-based grading system for stage pT1 NMIBC that correlates with disease aggressiveness and oncological patient outcomes. It therefore identifies a highest risk group of stage pT1 NMIBC patients, who should be followed up more intensively or receive immediate radical cystectomy. The grading incorporates objective variables assessable on haematoxylin and eosin slides and immunohistochemistry, enabling an easy-to-use low-cost approach that is applicable in daily routine. Further studies are needed to validate and confirm these results.

Improving detection of carcinoma in situ in bladder cancer: urinary cytology vs the Xpert® BC Monitor.

OBJECTIVE: To investigate and compare the performance of urinary cytology and the Xpert BC Monitor test in the detection of bladder cancer in various clinically significant patient cohorts, including patients with carcinoma in situ (CIS), in a prospective multicentre setting, aiming to identify potential applications in clinical practice. PATIENTS AND METHODS: A total of 756 patients scheduled for transurethral resection of bladder tumour (TURBT) were prospectively screened between July 2018 and December 2020 at six German University Centres. Central urinary cytology and Xpert BC Monitor tests were performed prior to TURBT. The diagnostic performance of urinary cytology and the Xpert BC Monitor was evaluated according to sensitivity (SN), specificity (SC), negative predictive value (NPV) and positive predictive value (PPV). Statistical comparison of urinary cytology and the Xpert BC Monitor was conducted using the McNemar test. RESULTS: Of 756 screened patients, 733 (568 male [78%]; median [interquartile range] age 72 [62-79] years) were included. Bladder cancer was present in 482 patients (65.8%) with 258 (53.5%) high-grade tumours. Overall SN, SC, NPV and PPV were 39%, 93%, 44% and 92% for urinary cytology, and 75%, 69%, 59% and 82% for the Xpert BC Monitor. In patients with CIS (concomitant or solitary), SN, SC, NPV and PPV were 59%, 93%, 87% and 50% for urinary cytology, and 90%, 69%, 95% and 50% for the Xpert BC Monitor. The Xpert BC Monitor missed four tumours (NPV = 98%) in patients with solitary CIS, while potentially avoiding 63.3% of TURBTs in inconclusive or negative cystoscopy and a negative Xpert result. CONCLUSION: Positive urinary cytology may indicate bladder cancer and should be taken seriously. The Xpert BC Monitor may represent a useful diagnostic tool for correctly identifying patients with solitary CIS and unsuspicious or inconclusive cystoscopy.

Ureteroplasty with buccal mucosa graft without omental wrap: an effective method to treat ureteral strictures.

PURPOSE: Successful treatment options for ureteral strictures are limited. Surgical options such as ileal interposition and kidney autotransplantation are difficult and associated with morbidity and complications. Techniques such as Boari flap and psoas hitch are limited to distal strictures. Only limited case studies on the success of open buccal mucosa graft (BMG) ureteroplasty exist to this date. The purpose of this study was to evaluate the success of open BMG ureteroplasty without omental wrap. METHODS: In this single-center retrospective study between July 2020 and January 2023, we included 14 consecutive patients with ureteric strictures who were treated with open BMG ureteroplasty without omental wrap. The primary outcome was the success of open BMG ureteroplasty. Further endpoints were complications and hospital readmission. Outcome variables were assessed by clinical examination, kidney sonography, and patient anamnesis. RESULTS: Out of 14 patients, 13 were stricture and ectasia-free without a double-J stent at a median follow-up of 15 months (success rate 93%). No complications were observed at the donor site, and the complication rate overall was low with 3 out of 14 patients (21%) having mild-to-medium complications. CONCLUSIONS: Open BMG ureteroplasty without omental wrap is a successful and feasible technique for ureteric stricture repair.

Risk factors for bladder neck contracture after transurethral resection of the prostate.

INTRODUCTION: Transurethral resection of the prostate (TURP) is the most frequently used treatment of benign prostate hyperplasia with a prostate volume of <80 mL. A long-term complication is bladder neck contracture (BNC). The aim of the present study was to identify the risk factors for BNC formation after TURP. METHODS: We conducted a retrospective analysis of all TURP primary procedures which were performed at one academic institution between 2013 and 2018. All patients were analyzed and compared with regard to postoperative formation of a BNC requiring further therapy. Uni- and multivariable logistic regression analyses (MVAs) were performed to identify possible risk factors for BNC development. RESULTS: We included 1368 patients in this analysis. Out of these, 88 patients (6.4%) developed BNC requiring further surgical therapy. The following factors showed a statistically significant association with BNC development: smaller preoperative prostate volume (p = 0.001), lower resected prostate weight (p = 0.004), lower preoperative levels of prostate-specific antigen (PSA, p < 0.001), shorter duration of the surgery (p = 0.027), secondary transurethral intervention (due to urinary retention or gross hematuria) during inpatient stay (p = 0.018), positive (≥100 CFU/mL) preoperative urine culture (p = 0.010), and urethral stricture (US) formation requiring direct visual internal urethrotomy (DVIU) postoperatively after TURP (p < 0.001), in particular membranous (p = 0.046) and bulbar (p < 0.001) strictures. Preoperative antibiotic treatment showed a protective effect (p = 0.042). Histopathological findings of prostate cancer (PCA) in the resected prostate tissue were more frequent among patients who did not develop BNC (p = 0.049). On MVA, smaller preoperative prostate volume (p = 0.046), positive preoperative urine culture (p = 0.021), and US requiring DVIU after TURP (p < 0.001) were identified as independent predictors for BNC development. CONCLUSION: BNC is a relevant long-term complication after TURP. In particular, patients with a smaller prostate should be thoroughly informed about this complication.

Short-Term and Long-Term Morbidity after Radical Cystectomy in Patients with NMIBC and Comparison with MIBC: Identifying Risk Factors for Severe Short-Term Complications.

INTRODUCTION: RC represents a viable treatment option for certain NMIBC patients. However, studies investigating morbidity in the context of RC for NMIBC are scarce. The goal of the current study was to assess and compare morbidity after RC performed in patients with NMIBC and patients with MIBC and to identify risk factors for severe short-term complications. METHODS: Medical records of 521 patients who underwent RC for bladder cancer were retrospectively reviewed. Patients were divided into patients with NMIBC and patients with MIBC. The groups were compared and risk factors for severe complications were identified. RESULTS: RC for NMIBC was performed in 123 patients (23.6%). Histological upstaging was seen in 47 NMIBC patients (38.2%) and in 231 MIBC patients (58%, p < 0.001). OS was 29.8% and CSS was 15.5%. Both endpoints were higher for RC for MIBC (p < 0.001). More complications affecting the urinary diversion were seen with RC for NMIBC (p = 0.033) and more continent urinary diversions (p = 0.040) were performed in those patients. Obesity (p = 0.008), a higher ASA score (p = 0.004), and preoperative medical drug anticoagulation (p = 0.025) were risk factors for severe short-term morbidity after both, RC for NMIBC and for MIBC. CONCLUSION: Patients who underwent RC for NMIBC are exposed to a comparably high perioperative risk than patients with MIBC. RC seems to be a viable treatment option for certain NMIBC patients with a significant histological upstaging in both groups. In patients with obesity, a high ASA score, and with medical drug anticoagulation, the indication for surgery should be confirmed especially strict and possible treatment alternatives should be considered particularly thorough.

I could do it now, but I'd rather (forget to) do it later: examining links between procrastination and prospective memory failures.

Prospective memory (PM) represents the ability to remember to perform planned actions after a certain delay. As previous studies suggest that even brief task-delays can negatively affect PM performance, the current study set out to examine whether procrastination (intentionally delaying task execution despite possible negative consequences) may represent a factor contributing to PM failures. Specifically, we assessed procrastination (via a standardized questionnaire as well as an objective behavioral measure) and PM failures (via a naturalistic PM task) in 92 young adults. Results show that participants' self-reports as well as their actual procrastination behavior predicted the number of PM failures, corroborating the impact of procrastination on PM. Subsequent cluster analyses suggest three distinct procrastination profiles (non-procrastinators, conscious procrastinators and unconscious procrastinators), providing new conceptual insights into different mechanisms of how procrastinating may lead to forgetting to perform planned tasks.

Prospective memory errors in everyday life: does instruction matter?

Previous research on prospective memory (PM, the ability to remember executing an intention in the future) suggests that PM errors constitute the majority of all everyday memory errors in younger adults. However, no study so far has investigated this ratio from an ageing perspective, nor examined whether different instructions may influence PM error reporting. In the present study, 64 younger and 64 older adults completed a 5-day diary on PM, memory and cognition errors following different reporting instructions: participants had to either focus on (1) PM errors only, (2) any daily memory errors (prospective or retrospective) or (3) any kind of cognitive error. Error descriptions were coded into subcategories and analysed both quantitatively and qualitatively. Independently of given instructions, PM was the most frequent everyday error for both age groups. Overall, results confirm age differences for everyday PM (but not for retrospective memory and cognition), suggesting that everyday PM might be spared from age-related decline. From a qualitative point of view, there seem to be differences in the type of missed intentions, which correspond with existent theories of ageing. In conclusion, the present study allowed for a deeper insight into everyday PM functioning in younger and older adults.

Prospective Memory Relates to Attentional Control: Differential Patterns in Old Age.

AIMS: We investigated the associations of prospective memory (PM) with memory, attentional control, and conscientiousness and whether they differed between young-old (YO) and old-old adults (OO). METHODS: We analyzed data from 562 older adults (mean = 80.04 years) who were tested on four PM tasks, memory (immediate and delayed cued recall), attentional control (letter and category fluency), and reported conscientiousness. RESULTS: Latent variable analyses showed that in both YO and OO PM was associated with memory and attentional control (but not conscientiousness). Notably, testing for moderation effects revealed that the relation between PM and attentional control was significantly stronger in YO than in OO. CONCLUSION: YO may be able to better (than OO) achieve a good PM performance with good attentional control.

Glenoid morphology is associated with the development of instability arthropathy.

BACKGROUND: Instability arthropathy (IA) is a major long-term concern in patients with anterior shoulder instability. This study investigated the association of glenoid morphology with the development of IA. METHODS: The study included 118 patients with unilateral anterior shoulder instability and available bilateral computed tomography scans. Instability-specific information was obtained from all patients. The glenoid morphology of the affected shoulder was compared with the nonaffected contralateral side resembling the constitutional preinjury glenoid shape. Both shoulders were evaluated independently by 3 observers to assess the grade of IA according to a Comprehensive Arthropathy Rating (CAR) system. Associations between IA and the glenoid morphology parameters were investigated. RESULTS: The average glenoid retroversion (P < .001), glenoid depth (P < .001), glenoid diameter (P < .001), and the bony shoulder stability ratio (P < .001) of the affected shoulder were significantly reduced compared with the contralateral side due to bony defects in 79.6% of the patients. The CAR of the affected side was significantly higher (P < .001), with more osteophytes (P = .001) and more sclerosis and cysts (P < .001). Differences in CAR (Δ-CAR) correlated positively with the age at the time of the computed tomography scan (P < .001), age at the initial dislocation (P = .001), size of the glenoid defect (P = .005), and the contralateral glenoid depth (P = .011), glenoid diameter (P = .016), and bony shoulder stability (P = .029), and negatively with glenoid retroversion of the affected side (P = .027). CONCLUSION: Development of IA arthropathy is associated not only with the age of the patients but also with morphologic parameters of the glenoid, including glenoid defect size and the constitutional glenoid concavity shape.

Na+/H+ Exchangers Are Required for the Development and Function of Vertebrate Mucociliary Epithelia.

Na+/H+ exchangers (NHEs) represent a highly conserved family of ion transporters that regulate pH homeostasis. NHEs as well as other proton transporters were previously linked to the regulation of the Wnt signaling pathway, cell polarity signaling, and mucociliary function. Furthermore, mutations in the gene SLC9A3 (encoding NHE3) were detected as additional risk factors for airway infections in cystic fibrosis patients. Here, we used the Xenopus embryonic mucociliary epidermis as well as human airway epithelial cells (HAECs) as models to investigate the functional roles of NHEs in mucociliary development and regeneration. In Xenopus embryos, NHEs 1-3 were expressed during epidermal development, and loss of NHE function impaired mucociliary clearance in tadpoles. Clearance defects were caused by reduced cilia formation, disrupted alignment of basal bodies in multiciliated cells (MCCs), and dysregulated mucociliary gene expression. These data also suggested that NHEs may contribute to the activation of Wnt signaling in mucociliary epithelia. In HAECs, pharmacological inhibition of NHE function also caused defective ciliation and regeneration in airway MCCs. Collectively, our data revealed a requirement for NHEs in vertebrate mucociliary epithelia and linked NHE activity to cilia formation and function in differentiating MCCs. Our results provide an entry point for the understanding of the contribution of NHEs to signaling, development, and pathogenesis in the human respiratory tract.

Human WIPI ß-propeller function in autophagy and neurodegeneration.

The four human WIPI ß-propellers, WIPI1 through WIPI4, belong to the ancient PROPPIN family and fulfill scaffold functions in the control of autophagy. In this context, WIPI ß-propellers function as PI3P effectors during autophagosome formation and loss of WIPI function negatively impacts autophagy and contributes to neurodegeneration. Of particular interest are mutations in WDR45, the human gene that encodes WIPI4. Sporadic WDR45 mutations are the cause of a rare human neurodegenerative disease called BPAN, hallmarked by high brain iron accumulation. Here, we discuss the current understanding of the functions of human WIPI ß-propellers and address unanswered questions with a particular focus on the role of WIPI4 in autophagy and BPAN.

From attentional fluctuations to intentional fluctuations? Monitoring behavior and intraindividual variability in time-based prospective memory.

In sharp contrast to event-based prospective memory (PM), dynamics of (re)allocation of attention between the ongoing and PM tasks have been much less investigated in time-based PM tasks. We propose an in-depth examination of attention allocation in a time-based PM task by jointly analyzing multiple indicators of time-monitoring behavior, net and time-structured intraindividual variability (IIV) in ongoing-task reaction times (OT RTs), and task performance. Results from dynamic structural equation modeling in a lifespan sample of 198 adults (19-86 years) revealed that larger fluctuations in OT RTs (net IIV) predicted poorer OT performance, but fostered a more efficient pattern of time-monitoring behavior (i.e., checking a clock more frequently and strategically, and slowing OT RTs during the PM response window) that, in turn, enhanced PM. Conversely, greater inertia in OT RTs (time-structured IIV) led to fewer clock-checks and poorer PM performance. Focusing attention on time monitoring to enhance PM performance did not detrimentally affect OT accuracy. Instead, participants showed a speed-accuracy tradeoff to optimize both OT and PM accuracies by slowing their OT RTs during the PM response window. This study therefore shows that two concomitant aspects of IIV (net and time-structured IIV) not only predicted time-monitoring behavior, but also OT and PM accuracies differentially, hence advocating for the necessity to consider both aspects of IIV and time monitoring together to better understand attention allocation policies in time-based PM tasks. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Autophagy profiling in single cells with open source CellProfiler-based image analysis.

Single cell-based analysis of macroautophagy/autophagy is largely achieved through the use of fluorescence microscopy to detect autophagy-related proteins that associate with autophagic membranes and therefore can be quantified as fluorescent puncta. In this context, an automated analysis of the number and size of recognized puncta is preferable to a manual count, because more reliable results can be generated in a short time. Here we present a method for open source CellProfiler software-based analysis for quantitative autophagy assessments using GFP-tagged WIPI1 (WD repeat domain, phosphoinositide interacting 1) images acquired with Airyscan or confocal laser-scanning microscopy. The CellProfiler protocol is provided as a ready-to-use software pipeline, and the creation of this pipeline is detailed in both text and video formats. In addition, we provide CellProfiler pipelines for endogenous SQSTM1/p62 (sequestosome 1) or intracellular lipid droplet (LD) analysis, suitable to assess forms of selective autophagy. All protocols and software pipelines can be quickly and easily adapted for the use of alternative autophagy markers or cell types, and can also be used for high-throughput purposes.Abbreviations: AF Alexa Fluor ATG autophagy related BafA1 bafilomycin A1 BSA bovine serum albumin DAPI 4,6-diamidino-2-phenylindole DMEM Dulbecco's modified Eagle's medium DMSO dimethyl sulfoxide EDTA ethylenediaminetetraacetic acid EBSS Earle's balanced salt solution FBS fetal bovine serum GFP green fluorescent protein LD lipid droplet LSM laser scanning microscope MAP1LC3B microtubule associated protein 1 light chain 3 beta MTOR mechanistic target of rapamycin kinase PBS phosphate-buffered saline PIK3C3/VPS34 phosphatidylinositol 3-kinase catalytic subunit type 3 SQSTM1 sequestosome 1 TIFF tagged image file format U2OS U-2 OS cell line WIPI WD repeat domain, phosphoinositide interacting.

Temporal Notch signaling regulates mucociliary cell fates through Hes-mediated competitive de-repression.

Tissue functions are determined by the types and ratios of cells present, but little is known about self-organizing principles establishing correct cell type compositions. Mucociliary airway clearance relies on the correct balance between secretory and ciliated cells, which is regulated by Notch signaling across mucociliary systems. Using the airway-like Xenopus epidermis, we investigate how cell fates depend on signaling, how signaling levels are controlled, and how Hes transcription factors regulate cell fates. We show that four mucociliary cell types each require different Notch levels and that their specification is initiated sequentially by a temporal Notch gradient. We describe a novel role for Foxi1 in the generation of Delta-expressing multipotent progenitors through Hes7.1. Hes7.1 is a weak repressor of mucociliary genes and overcomes maternal repression by the strong repressor Hes2 to initiate mucociliary development. Increasing Notch signaling then inhibits Hes7.1 and activates first Hes4, then Hes5.10, which selectively repress cell fates. We have uncovered a self-organizing mechanism of mucociliary cell type composition by competitive de-repression of cell fates by a set of differentially acting repressors. Furthermore, we present an in silico model of this process with predictive abilities.

Body Composition of Patients Undergoing Radical Cystectomy for Bladder Cancer: Sarcopenia, Low Psoas Muscle Index, and Myosteatosis Are Independent Risk Factors for Mortality.

BACKGROUND: We assessed a wide array of body composition parameters to identify those most relevant as prognostic tools for patients undergoing radical cystectomy (RC) due to bladder cancer (BC). METHODS: In this retrospective, single-center study, preoperative computed tomography (CT) scans of 657 patients were measured at the level of the 3rd lumbar vertebra (L3) to determine common body composition indices including sarcopenia, myosteatosis, psoas muscle index (PMI), subcutaneous and visceral fat index (SFI and VFI), visceral-to-subcutaneous fat ratio (VSR), and visceral obesity. Predictors of overall survival (OS) and cancer-specific survival (CSS) were identified in univariate and multivariate survival analysis. RESULTS: Sarcopenia and a low PMI were independently associated with shorter OS (Sarcopenia: HR 1.30; 95% CI 1.02-1.66; p = 0.04 and a low PMI: HR 1.32; 95% CI 1.02-1.70; p = 0.03) and CSS (Sarcopenia: HR 1.64; 95% CI 1.19-2.25; p < 0.01 and a low PMI: HR 1.41; 95% CI 1.02-1.96; p = 0.04). Myosteatosis, measured as decreasing average Hounsfield units of skeletal muscle, was an independent risk factor for OS (HR 0.98; 95% CI 0.97-1.00; p = 0.01) and CSS (HR 0.98; 95% CI 0.96-1.00; p < 0.05). The assessed adipose tissue indices were not significant predictors for OS and CSS. CONCLUSIONS: Sarcopenia, a low PMI, and myosteatosis are independent predictors for OS and CSS in patients undergoing radical cystectomy for bladder cancer.

Body Composition as a Comorbidity-Independent Predictor of Survival following Nephroureterectomy for Urothelial Cancer of the Upper Urinary Tract.

Radical nephroureterectomy (NUE) is the gold standard treatment for high-risk urothelial cancer of the upper urinary tract (UTUC). Besides sarcopenia and frailty, fat distribution is moving increasingly into focus. Components of body composition were assessed in patients undergoing NUE due to UTUC. The study cohort included 142 patients. By using CT-based measurements, the skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI) were measured at the height of the third lumbar vertebra. Overall survival (OS) and cancer-specific survival (CSS) were estimated using univariable und multivariable Cox regression models. The prevalence of sarcopenia in the study population (n = 142) was 37%. OS and CSS were significantly reduced in sarcopenic patients. In the multivariable cox regression analysis, including age, ACE-27, T-stage, R-stage, LVI and necrosis, sarcopenia remained a significant risk factor of OS (HR, 1.77; 95% CI 1.02-3.07; p = 0.042) and CSS (HR, 2.17; 95% CI 1.18-3.99; p = 0.012). High visceral adipose tissue seems to be protective, although not statistically significant. Sarcopenia is a comorbidity-independent risk factor in patients who underwent NUE due to UTUC. Visceral fat represents a potentially protective factor. These results suggest that specific factors of body composition can be used for better risk stratification.

Xpert bladder cancer monitor to predict the need for a second TURB (MoniTURB trial).

To determine whether Xpert bladder cancer monitor, a noninvasive PCR-based biomarker test, can predict the need for 2nd transurethral resection of the bladder (TURB) better than clinical assessment. Patients scheduled for TURB were prospectively screened. After initial TURB, patients were assigned to 2nd TURB or follow-up cystoscopy at 3 months (FU) by clinicians' discretion. Central urine cytology and Xpert monitor tests were performed prior to the 1st TURB and 2nd TURB or FU, respectively. Statistical analysis to compare clinical assessment and Xpert monitor comprised sensitivity (SENS), specificity (SPEC), NPV and PPV. Of 756 screened patients, 171 were included (114 with 2nd TURB, 57 with FU). Residual tumors were detected in 34 patients who underwent 2nd TURB, and recurrent tumors were detected in 2 patients with FU. SENS and SPEC of Xpert monitor were 83.3% and 53.0%, respectively, PPV was 32.6% and NPV was 92.1%. Clinical risk assessment outperformed Xpert monitor. In patients with pTa disease at initial TURB, Xpert monitor revealed a NPV of 96%. Xpert monitor was not superior than clinical assessment in predicting the need for 2nd TURB. It might be an option to omit 2nd TURB for selected patients with pTa disease.

The ABL-MYC axis controls WIPI1-enhanced autophagy in lifespan extension.

Human WIPI ß-propellers function as PI3P effectors in autophagy, with WIPI4 and WIPI3 being able to link autophagy control by AMPK and TORC1 to the formation of autophagosomes. WIPI1, instead, assists WIPI2 in efficiently recruiting the ATG16L1 complex at the nascent autophagosome, which in turn promotes lipidation of LC3/GABARAP and autophagosome maturation. However, the specific role of WIPI1 and its regulation are unknown. Here, we discovered the ABL-ERK-MYC signalling axis controlling WIPI1. As a result of this signalling, MYC binds to the WIPI1 promoter and represses WIPI1 gene expression. When ABL-ERK-MYC signalling is counteracted, increased WIPI1 gene expression enhances the formation of autophagic membranes capable of migrating through tunnelling nanotubes to neighbouring cells with low autophagic activity. ABL-regulated WIPI1 function is relevant to lifespan control, as ABL deficiency in C. elegans increased gene expression of the WIPI1 orthologue ATG-18 and prolonged lifespan in a manner dependent on ATG-18. We propose that WIPI1 acts as an enhancer of autophagy that is physiologically relevant for regulating the level of autophagic activity over the lifespan.

Frequency and strategicness of clock-checking explain detrimental age effects in time-based prospective memory.

Previous studies report that monitoring the passing of time by checking a clock either frequently or strategically (immediately before a target time) improves the likelihood of remembering to perform a planned intention at a specific time (i.e., time-based prospective memory [TBPM]). Critically, strategicness of clock-checking is usually measured as the number of clock-checks during the last time interval before the target time-an operationalization where strategicness actually intertwines with absolute frequency of clock-checking and may not properly account for age effects in TBPM performance. To disentangle the respective contribution of frequent versus strategic clock-checking to the age-related decrease in TBPM performance, we propose a new, more fine-grained indicator of strategicness (i.e., relative clock-checking), which accounts for interindividual differences in the total frequency of clock-checking (i.e., absolute clock-checking). In this study, 223 participants from an adult lifespan sample (age range = 19-86, M = 45.61, SD = 17.24; 70% women) had to remember to push the ENTER key every 60 s while performing a two-back picture decision task. Together, relative and absolute clock-checking fully mediated the negative age effect on TBPM and explained 53.6% of the variance of TBPM performance. Complementary analyses revealed that both indicators were needed to fully mediate the effect of age on TBPM, but that strategic (i.e., relative) clock-checking was a stronger predictor of TBPM performance than absolute clock-checking. These results stress the importance of considering both aspects of clock-checking to investigate time monitoring in laboratory TBPM tasks and age effects therein, and provide avenues of intervention for improving older adults' TBPM. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The Sounds of Memory: Extending the Age-Prospective Memory Paradox to Everyday Behavior and Conversations.

OBJECTIVES: Around the turn of the millennium, the "age-prospective memory (PM) paradox" challenged the classical assumption that older adults necessarily evidence a marked decline in PM functioning. As previous investigations highlighted ecological validity to be a potential explanation, the present study sought to extend established approaches by using novel real-world assessment technologies to examine PM unobtrusively in everyday-life conversations. METHOD: Next to laboratory PM tasks, real-life PM performance of 53 younger adults (19-32 years) and 38 older adults (60-81 years) was assessed from three sources: Over 9 days, participants completed an experimenter-given naturalistic task, a diary-based approach assessing self-assigned intentions, as well as an ambulatory assessment with the Electronically Activated Recorder (EAR), a device that unobtrusively samples ambient sounds to detect spontaneous speech production related to (lapses in) everyday PM. RESULTS: Older adults showed lower performance in laboratory PM only for the time-based task and performed either equally well as or even better than younger adults in everyday PM. With regard to PM performance as captured in real-life ambient audio data, younger adults talked more frequently about PM than older adults, but no significant difference between younger and older adults was found for speech related to PM errors. DISCUSSION: Findings confirmed older adults' preserved PM performance in everyday life across different indicators with increasing ecological validity. Furthermore, as a novel method to assess conversational PM in everyday life, the EAR opens new insights about the awareness of PM lapses and the communication of intentions in real life.