Optimal use of reminders: Metacognition, effort, and cognitive offloading

Individuals frequently choose between accomplishing goals using unaided cognitive abilities or offloading cognitive demands onto external tools and resources. For example, in order to remember an upcoming appointment one might rely on unaided memory or create a reminder by setting a smartphone alert. Setting a reminder incurs both a cost (the time/effort to set it up) and a benefit (increased likelihood of remembering). Here we investigate whether individuals weigh such costs/benefits optimally or show systematic biases. In 3 experiments, participants performed a memory task where they could choose between (a) earning a maximum reward for each remembered item, using unaided memory; or (b) earning a lesser amount per item, using external reminders to increase the number remembered. Participants were significantly biased toward using external reminders, even when they had a financial incentive to choose optimally. Individual differences in this bias were stable over time, and predicted by participants' erroneous metacognitive underconfidence in their memory abilities. Bias was eliminated, however, when participants received metacognitive advice about which strategy was likely to maximize performance. Furthermore, we found that metacognitive interventions (manipulation of feedback valence and practice-trial difficulty) yielded shifts in participants' reminder bias that were mediated by shifts in confidence. However, the bias could not be fully attributed to metacognitive error. We conclude that individuals have stable biases toward using external versus internal cognitive resources, which result at least in part from inaccurate metacognitive evaluations. Finding interventions to mitigate these biases can improve individuals' adaptive use of cognitive tools

Microneedle Enhanced Delivery of Cosmeceutically Relevant Peptides in Human Skin

Peptides and proteins play an important role in skin health and well-being. They are also found to contribute to skin aging and melanogenesis. Microneedles have been shown to substantially enhance skin penetration and may offer an effective means of peptide delivery enhancement. The aim of this investigation was to assess the influence of microneedles on the skin penetration of peptides using fluorescence imaging to determine skin distribution. In particular the effect of peptide chain length (3, 4, 5 amino acid chain length) on passive and MN facilitated skin penetration was investigated. Confocal laser scanning microscopy was used to image fluorescence intensity and the area of penetration of fluorescently tagged peptides. Penetration studies were conducted on excised full thickness human skin in Franz type diffusion cells for 1 and 24 hours. A 2 to 22 fold signal improvement in microneedle enhanced delivery of melanostatin, rigin and pal-KTTKS was observed. To our knowledge this is the first description of microneedle enhanced skin permeation studies on these peptides

Identification of differentially expressed microRNAs in human male breast cancer

<p>Abstract</p> <p>Background</p> <p>The discovery of small non-coding RNAs and the subsequent analysis of microRNA expression patterns in human cancer specimens have provided completely new insights into cancer biology. Genetic and epigenetic data indicate oncogenic or tumor suppressor function of these pleiotropic regulators. Therefore, many studies analyzed the expression and function of microRNA in human breast cancer, the most frequent malignancy in females. However, nothing is known so far about microRNA expression in male breast cancer, accounting for approximately 1% of all breast cancer cases.</p> <p>Methods</p> <p>The expression of 319 microRNAs was analyzed in 9 primary human male breast tumors and in epithelial cells from 15 male gynecomastia specimens using fluorescence-labeled bead technology. For identification of differentially expressed microRNAs data were analyzed by cluster analysis and selected statistical methods.</p> <p>Expression levels were validated for the most up- or down-regulated microRNAs in this training cohort using real-time PCR methodology as well as in an independent test cohort comprising 12 cases of human male breast cancer.</p> <p>Results</p> <p>Unsupervised cluster analysis separated very well male breast cancer samples and control specimens according to their microRNA expression pattern indicating cancer-specific alterations of microRNA expression in human male breast cancer. miR-21, miR519d, miR-183, miR-197, and miR-493-5p were identified as most prominently up-regulated, miR-145 and miR-497 as most prominently down-regulated in male breast cancer.</p> <p>Conclusions</p> <p>Male breast cancer displays several differentially expressed microRNAs. Not all of them are shared with breast cancer biopsies from female patients indicating male breast cancer specific alterations of microRNA expression.</p

Non-Invasive Exploration of Neonatal Gastric Epithelium by Using Exfoliated Epithelial Cells

Background &amp; Aims: In preterm infants, exfoliated gastric epithelial cells can be retrieved from aspirates sampled through the naso-gastric feeding tube. Our aims were to determine (1) whether the recovery of exfoliated cells is feasible at any time from birth through the removal of the nasogastric tube, (2) whether they can be grown in culture in vitro, and (3) whether the physiological state of exfoliated cells expressing H+/K+-ATPases reflects that of their counterparts remaining in situ at the surface of the gastric epithelium in neonatal rat pups. Methods: In infants, gastric fluid aspirates were collected weekly after birth or every 3 hours over 24-h periods, and related to clinical parameters (Biocollection PROG/09/18). In rat pups submitted to a single fasting/refeeding cycle, we explored circadian exfoliation with the cellular counter-parts in the gland. All samples were analyzed by confocal imaging and Enzyme-Linked Immunosorbent Assay. Results: Epithelial cells were identified by microscopy using membrane-bound anti-H+/K+ ATPases antibody, assessed for nucleus integrity, and the expression of selected proteins (autophagy, circadian clock). On 34 infants, the H+/K+-ATPasepositive cells were consistently found quiescent, regardless of gestational age and feeding schedule from day-5 of life to the day of removal of the naso-gastric tube. By logistic regression analysis, we did find a positive correlation between the intensity of exfoliation (cellular loss per sample) and the postnatal age (p,0.001). The H+/K+ ATPase-positive cell

Whole Exome Sequencing of HIV-1 long-term non-progressors identifies rare variants in genes encoding innate immune sensors and signaling molecules

Abstract Common CCR5-∆32 and HLA alleles only explain a minority of the HIV long-term non-progressor (LTNP) and elite controller (EC) phenotypes. To identify rare genetic variants contributing to the slow disease progression phenotypes, we performed whole exome sequencing (WES) on seven LTNPs and four ECs. HLA and CCR5 allele status, total HIV DNA reservoir size, as well as variant-related functional differences between the ECs, LTNPs, and eleven age- and gender-matched HIV-infected non-controllers on antiretroviral therapy (NCARTs) were investigated. Several rare variants were identified in genes involved in innate immune sensing, CD4-dependent infectivity, HIV trafficking, and HIV transcription mainly within the LTNP group. ECs and LTNPs had a significantly lower HIV reservoir compared to NCARTs. Furthermore, three LTNPs with variants affecting HIV nuclear import showed integrated HIV DNA levels below detection limit after in vitro infection. HIV slow progressors with variants in the TLR and NOD2 pathways showed reduced pro-inflammatory responses compared to matched controls. Low-range plasma levels of fibronectin was observed in a LTNP harboring two FN1 variants. Taken together, this study identified rare variants in LTNPs as well as in one EC, which may contribute to understanding of HIV pathogenesis and these slow progressor phenotypes, especially in individuals without protecting CCR5-∆32 and HLA alleles

Robust Biomarkers: Methodologically Tracking Causal Processes in Alzheimer’s Measurement

In biomedical measurement, biomarkers are used to achieve reliable prediction of, and useful causal information about patient outcomes while minimizing complexity of measurement, resources, and invasiveness. A biomarker is an assayable metric that discloses the status of a biological process of interest, be it normative, pathophysiological, or in response to intervention. The greatest utility from biomarkers comes from their ability to help clinicians (and researchers) make and evaluate clinical decisions. In this paper we discuss a specific methodological use of clinical biomarkers in pharmacological measurement: Some biomarkers, called ‘surrogate markers’, are used to substitute for a clinically meaningful endpoint corresponding to events and their penultimate risk factors. We confront the reliability of clinical biomarkers that are used to gather information about clinically meaningful endpoints. Our aim is to present a systematic methodology for assessing the reliability of multiple surrogate markers (and biomarkers in general). To do this we draw upon the robustness analysis literature in the philosophy of science and the empirical use of clinical biomarkers. After introducing robustness analysis we present two problems with biomarkers in relation to reliability. Next, we propose an intervention-based robustness methodology for organizing the reliability of biomarkers in general. We propose three relevant conditions for a robust methodology for biomarkers: (R1) Intervention-based demonstration of partial independence of modes: In biomarkers partial independence can be demonstrated through exogenous interventions that modify a process some number of “steps” removed from each of the markers. (R2) Comparison of diverging and converging results across biomarkers: By systematically comparing partially-independent biomarkers we can track under what conditions markers fail to converge in results, and under which conditions they successfully converge. (R3) Information within the context of theory: Through a systematic cross-comparison of the markers we can make causal conclusions as well as eliminate competing theories. We apply our robust methodology to currently developing Alzheimer’s research to show its usefulness for making causal conclusions

MicroRNA Dysregulation in the Spinal Cord following Traumatic Injury

Spinal cord injury (SCI) triggers a multitude of pathophysiological events that are tightly regulated by the expression levels of specific genes. Recent studies suggest that changes in gene expression following neural injury can result from the dysregulation of microRNAs, short non-coding RNA molecules that repress the translation of target mRNA. To understand the mechanisms underlying gene alterations following SCI, we analyzed the microRNA expression patterns at different time points following rat spinal cord injury