Identifying age-invariant and age-limited mechanisms for enhanced memory performance: Insights from self-referential processing in younger and older adults.

Self-referential processing has been identified as a possible tool for supporting effective encoding processes in the elderly population. However, the importance of self-reference per se, relative to the increase in meaningful elaboration normally associated with self-reference instructions, remains unclear. The present study sought to explore this issue further by examining self-referential encoding strategies that inherently involve more extensive stimulus elaboration: episodic autobiographical memory (AM) retrieval and semantic AM retrieval. These were compared with an analogous task involving retrieval of general semantic knowledge, as well as traditional binary self-referential and semantic encoding judgments. We found that both AM retrieval and general semantic retrieval at encoding resulted in substantial enhancements to recall and recognition memory of concrete nouns relative to binary encoding judgments across both age groups. Furthermore, older adults exhibited larger benefits from this additional elaboration than did younger adults, leading to elimination of age-related deficits in recognition memory. However, younger adults showed an additional boost to subsequent memory following episodic, relative to semantic, AM retrieval during free recall that was not exhibited by older adults. This may be because of greater demands on frontally mediated control processes and cognitive resources associated with the use of this strategy. Taken together, the results suggest that the mnemonic benefits associated with self-referential processing vary substantially depending on the specific nature of the encoding strategy, and suggest that, under certain conditions, semantic processing and self-referential processing are equally effective in mitigating age-related deficits in memory performance.This research was supported by the BBSRC [grant number BB/L02263X/1]. A.N.T. is supported by a Cambridge Commonwealth Trust scholarship, R.N.H. by the UK Medical Research Council programme grant MC-A060-5PR10, and J.S.S. by a James S. McDonnell Foundation Scholar award.This is the author accepted manuscript. The final version is available from the American Psychological Association via http://dx.doi.org/ http://dx.doi.org/10.1037/a003911

Neural evidence for age-related differences in representational quality and strategic retrieval processes.

Mounting behavioral evidence suggests that declines in both representational quality and controlled retrieval processes contribute to episodic memory decline with age. The present study sought neural evidence for age-related change in these factors by measuring neural differentiation during encoding of paired associates and changes in regional blood oxygenation level-dependent activity and functional connectivity during retrieval conditions that placed low (intact pairs) and high (recombined pairs) demands on controlled retrieval processes. Pattern similarity analysis revealed age-related declines in the differentiation of stimulus representations at encoding, manifesting as both reduced pattern similarity between closely related events and increased pattern similarity between distinct events. During retrieval, both groups increased recruitment of areas within the core recollection network when endorsing studied pairs, including the hippocampus and angular gyrus. In contrast, only younger adults increased recruitment of, and hippocampal connectivity with, lateral prefrontal regions during correct rejections of recombined pairs. These results provide evidence for age-related changes in representational quality and in the neural mechanisms supporting memory retrieval under conditions of high, but not low, control demand

The current prevalence of child sexual abuse worldwide: a systematic review and meta-analysis

Objectives: Systematic reviews on prevalence estimates of child sexual abuse (CSA) worldwide included studies with adult participants referring on a period of abuse of about 50years. Therefore we aimed to describe the current prevalence of CSA, taking into account geographical region, type of abuse, level of country development and research methods. Methods: We included studies published between 2002 and 2009 that reported CSA in children below 18years. We performed a random effects meta-analysis and analyzed moderator variables by meta-regression. Results: Fifty-five studies from 24 countries were included. According to four predefined types of sexual abuse, prevalence estimates ranged from 8 to 31% for girls and 3 to 17% for boys. Nine girls and 3 boys out of 100 are victims of forced intercourse. Heterogeneity between primary studies was high in all analyses. Conclusions: Our results based on most recent data confirm results from previous reviews with adults. Surveys in children offer most recent estimates of CSA. Reducing heterogeneity between studies might be possible by standardized measures to make data more meaningful in international comparison

Copper(II) Ions Increase Plasminogen Activator Inhibitor Type 1 Dynamics in Key Structural Regions That Govern Stability

© 2016 American Chemical Society. Plasminogen activator inhibitor type 1 (PAI-1) regulates the fibrinolysis pathway by inhibiting the protease activity of plasminogen activators. PAI-1 works in concert with vitronectin (VN), an extracellular protein that aids in localization of active PAI-1 to tissues. The Peterson laboratory demonstrated that Cu(II) and other transition metals modulate the stability of PAI-1, exhibiting effects that are dependent on the presence or absence of the somatomedin B (SMB) domain of VN. The study presented here dissects the changes in molecular dynamics underlying the destabilizing effects of Cu(II) on PAI-1. We utilize backbone amide hydrogen/deuterium exchange monitored by mass spectrometry to assess PAI-1 dynamics in the presence and absence of Cu(II) ions with and without the SMB domain of VN. We show that Cu(II) produces an increase in dynamics in regions important for the function and overall stability of PAI-1, while the SMB domain elicits virtually the opposite effect. A mutant form of PAI-1 lacking two N-terminal histidine residues at positions 2 and 3 exhibits similar increases in dynamics upon Cu(II) binding compared to that of active wild-type PAI-1, indicating that the observed structural effects are not a result of coordination of Cu(II) to these histidine residues. Finally, addition of Cu(II) results in an acceleration of the local unfolding kinetics of PAI-1 presumed to be on pathway to the latency conversion. The effect of ligands on the dynamics of PAI-1 adds another intriguing dimension to the mechanisms for regulation of PAI-1 stability and function

Use of Non-Steroidal Anti-Inflammatory Drugs That Elevate Cardiovascular Risk: An Examination of Sales and Essential Medicines Lists in Low-, Middle-, and High-Income Countries

PMCID: PMC3570554This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study

Objective To examine the presence and extent of small study effects in clinical osteoarthritis research

Impact of the SGLT2 inhibitor empagliflozin on urinary supersaturations in kidney stone formers (SWEETSTONE trial): protocol for a randomised, double-blind, placebo-controlled cross-over trial.

INTRODUCTION Kidney stones are a global healthcare problem. Given high recurrence rates and the morbidity associated with symptomatic stone disease, effective medical prophylaxis is clearly an unmet need. Explanatory analyses of randomised controlled trials with sodium/glucose cotransporter isoform 2 inhibitors indicated a 30%-50% reduced rate of stone events in patients with diabetes. Underlying mechanisms remain unclear. We aim to determine the effect of empagliflozin on urinary supersaturations in non-diabetic kidney stone formers to evaluate their therapeutic potential for recurrence prevention. We will provide first clinical trial evidence on whether urinary supersaturations are affected by empagliflozin in kidney stone formers. METHODS AND ANALYSIS The SWEETSTONE trial is a randomised, double-blind, placebo-controlled, cross-over, exploratory study to assess the impact of empagliflozin on urinary supersaturations of calcium oxalate, calcium phosphate and uric acid in kidney stone formers. We plan to include 46 non-diabetic adults (18-74 years) with ≥1 past kidney stone event and stone composition with ≥80% of calcium or ≥80% of uric acid. Patients with secondary causes of kidney stones or chronic kidney disease will be excluded. Eligible individuals will be randomised in equal proportions to receive either a 14-day treatment with 25 mg empagliflozin followed after the 2-6 weeks wash out period by a 14-day treatment with a matching placebo or the reverse procedure. Secondary outcomes will include electrolyte concentrations, renal function, mineral metabolism and glycaemic parameters, urinary volume and safety.Results will be presented as effect measures (95% CIs) with p values and hypothesis testing for primary outcomes (significance level 0.02). ETHICS AND DISSEMINATION The SWEETSTONE trial was approved by the Swiss ethics committee and Swissmedic. First results are expected in the fourth quarter of 2022. TRIAL REGISTRATION NUMBER NCT04911660; Pre-results

The effects of excluding patients from the analysis in randomised controlled trials: meta-epidemiological study

Objective To examine whether excluding patients from the analysis of randomised trials are associated with biased estimates of treatment effects and higher heterogeneity between trials

Declines in representational quality and strategic retrieval processes contribute to age-related increases in false recognition.

In a Yes/No object recognition memory test with similar lures, older adults typically exhibit elevated rates of false recognition. However, the contributions of impaired retrieval, relative to reduced availability of target details, are difficult to disentangle using such a test. The present investigation sought to decouple these factors by comparing performance on a Yes/No (YN) test to that on a Forced Choice (FC) test, which minimizes demands on strategic retrieval processes, enabling a more direct measure of the availability of object details. Older adults exhibited increased lure false recognition across test formats (Experiment 1), suggesting a decline in the availability of object details contributes to deficits in performance. Manipulating interference by varying the number of objects studied selectively enhanced performance in the FC test, resulting in matched performance across groups, whereas age differences in YN performance persisted (Experiment 2), indicating an additional contribution of impaired strategic retrieval. Consistent with differential sensitivity of test format to strategic retrieval and the quality of stimulus representations among older adults, variability in the quality of object representations, measured using a perceptual discrimination task, was selectively related to FC performance. In contrast, variability in memory control processes, as measured with tests of recall and executive function, was related to performance across test formats. These results suggest that both declines in the availability of object details and impaired retrieval of object details contribute to elevated rates of lure false recognition with age, and highlight the utility of test format for dissociating these factors in memory-impaired populations. (PsycINFO Database RecordThis research was supported by the BBSRC [grant number BB/L02263X/1]. A.N.T. is supported by a Cambridge Commonwealth Trust scholarship, R.N.H. by the UK Medical Research Council programme grant MC-A060-5PR10, and J.S.S. by a James S. McDonnell Foundation Scholar award