Through the Ear, to the Brain: How Cognitive Aging Impacts Veridical and False Hearing in the Presence of Misleading Context

A consistent finding in the literature (Benichov, Cox, Tun, & Wingfield, 2012; Dubno, Ahlstrom, & Horwitz, 2000; Hutchinson, 1989; Nittrouer & Boothroyd, 1990; Pichora-Fuller, Schneider & Daneman, 1995; Rogers, Jacoby, & Sommers, 2012; Sommers & Danielson, 1999; Wingfield, Aberdeen, & Stine, 1991) is that spoken word identification improves for both older and younger adults following the addition of a meaningful semantic context, but the improvements are typically greater for older adults. However, more recent findings (Jacoby, Rogers, Bishara, & Shimizu, 2012; Rogers, Jacoby, & Sommers, 2012) suggest that, especially under less favorable perceptual conditions, the increased benefits of semantic context for older compared with younger adults may reflect increased reliance on context as a basis for responding, rather than improved ability to use contextual information. This increased reliance on context makes older adults prone to context-based misperceptions – termed false hearing – when context is misleading. Although increased reliance on context by older adults has been described as a strategy for “filling in the blanks” caused by age-related declines in hearing acuity, few researchers have investigated the relationship between reliance on context and age-related changes in cognitive abilities. The present study examined the effects of working memory capacity, processing speed, and inhibitory control on veridical and false hearing in older and younger adults. We found that poor inhibitory control was related to increased susceptibility to false hearing among both older and younger adults. For older adults, slower processing speed was also related to increased susceptibility to false hearing, whereas higher working memory capacity and preserved inhibitory control corresponded to more accurate speech perception in the presence of misleading context. We propose that older adults’ reliance on context may reflect a change in the relative weights assigned to contextual and sensory information during perception, wherein available contextual cues receive greater weight than sensory information. This reweighing of perceptual information may occur due to a combination of age-related hearing loss, which increases listening effort, and cognitive decline, which limits the resources available for effortful listening

Testing the Common-Mechanisms Theory of False Hearing and False Memory: The Roles of Executive Functioning and Inhibitory Control

Recent studies have shown that older adults are more susceptible to context-based misperceptions in hearing than are younger adults, a phenomenon that has been referred to as false hearing (Rogers et al., 2012; Sommers et al., 2015). The authors of these studies have noted similarities between false hearing and false memories (Jacoby et al., 2005), suggesting that the two phenomena may arise from similar cognitive mechanisms. The present dissertation project investigated similarities between false hearing and false memories. In Experiment 1, I directly compared susceptibility to false hearing and false memories in younger and older adults. I then investigated two cognitive mechanisms that could underlie these phenomena: inhibitory control and executive functioning. I found that poorer executive functioning was related to increased susceptibility to both false hearing and false memory, supporting executive functioning as a common cognitive mechanism underlying these phenomena. In Experiment 2, I tested whether the predictive strength of sentences influenced susceptibility to false hearing, building upon the finding of a strong relationship between backwards associative strength and susceptibility to false memory (Deese, 1959; Roediger et al., 2001b). I found that the predictive strength of sentences was positively associated with susceptibility to false hearing, supporting the idea that increasing inhibitory control demands increased the likelihood that false hearing would occur. Finally, I present eye-tracking data suggesting that predictive sentences increased activation of a single word, and that older adults were less likely than younger adults to suppress this activation when a different word was presented. The findings of these experiments support the idea that false hearing and false memory share at least one common cognitive mechanism, but highlight differences between these phenomena and between younger and older adults

Evaluation of Various Herbicides and Wilt Fungus (Cephalosporium Diospyri, Crandall) for Control of Persimmon (Diospyrous Virginiana, L.)

Agronom

A soft wearable robotic exoskeleton for rehabilitation of the frozen shoulder

Adhesive capsulitis (or "frozen shoulder"), is a joint condition resulting in pain and reduction to range of motion (ROM). Contemporary treatments can be effective but currently suffer from a number of drawbacks, including: high cost, lengthy treatment; lack of specificity to each patient; and lack of consistent, repetitive treatment between clinics and therapists [1]. Researchers are thus working to combat these drawbacks by developing rehabilitation exoskeletons. Traditional exoskeletons however aren’t always suitable, being rigid and heavy. Soft robotics may be suitable to overcome all of the above problems, combining the best of robotics (consistency, specificity) while being affordable and wearable through lightweight, compliant materials and design. A direction for the project has been presented, focusing on a pneumatic-based shoulder rehabilitation device, using IMUs as a primary sensor for feedback and control. There will be further detailed research into pneumatics, followed by CAD development to determine an appropriate and effective design. A prototype will be completed by the end of 2018

New trends for metal complexes with anticancer activity

Medicinal inorganic chemistry can exploit the unique properties of metal ions for the design of new drugs. This has, for instance, led to the clinical application of chemotherapeutic agents for cancer treatment, such as cisplatin. The use of cisplatin is, however, severely limited by its toxic side-effects. This has spurred chemists to employ different strategies in the development of new metal-based anticancer agents with different mechanisms of action. Recent trends in the field are discussed in this review. These include the more selective delivery and/or activation of cisplatin-related prodrugs and the discovery of new non-covalent interactions with the classical target, DNA. The use of the metal as scaffold rather than reactive centre and the departure from the cisplatin paradigm of activity towards a more targeted, cancer cell-specific approach, a major trend, are discussed as well. All this, together with the observation that some of the new drugs are organometallic complexes, illustrates that exciting times lie ahead for those interested in ‘metals in medicine

Current applications and future potential for bioinorganic chemistry in the development of anticancer drugs

This review illustrates notable recent progress in the field of medicinal bioinorganic chemistry as many new approaches to the design of innovative metal-based anticancer drugs are emerging. Current research addressing the problems associated with platinum drugs has focused on other metal-based therapeutics that have different modes of action and on prodrug and targeting strategies in an effort to diminish the side-effects of cisplatin chemotherapy

Abnormal expression of p27kip1 protein in levator ani muscle of aging women with pelvic floor disorders – a relationship to the cellular differentiation and degeneration

BACKGROUND: Pelvic floor disorders affect almost 50% of aging women. An important role in the pelvic floor support belongs to the levator ani muscle. The p27/kip1 (p27) protein, multifunctional cyclin-dependent kinase inhibitor, shows changing expression in differentiating skeletal muscle cells during development, and relatively high levels of p27 RNA were detected in the normal human skeletal muscles. METHODS: Biopsy samples of levator ani muscle were obtained from 22 symptomatic patients with stress urinary incontinence, pelvic organ prolapse, and overlaps (age range 38–74), and nine asymptomatic women (age 31–49). Cryostat sections were investigated for p27 protein expression and type I (slow twitch) and type II (fast twitch) fibers. RESULTS: All fibers exhibited strong plasma membrane (and nuclear) p27 protein expression. cytoplasmic p27 expression was virtually absent in asymptomatic women. In perimenopausal symptomatic patients (ages 38–55), muscle fibers showed hypertrophy and moderate cytoplasmic p27 staining accompanied by diminution of type II fibers. Older symptomatic patients (ages 57–74) showed cytoplasmic p27 overexpression accompanied by shrinking, cytoplasmic vacuolization and fragmentation of muscle cells. The plasma membrane and cytoplasmic p27 expression was not unique to the muscle cells. Under certain circumstances, it was also detected in other cell types (epithelium of ectocervix and luteal cells). CONCLUSIONS: This is the first report on the unusual (plasma membrane and cytoplasmic) expression of p27 protein in normal and abnormal human striated muscle cells in vivo. Our data indicate that pelvic floor disorders are in perimenopausal patients associated with an appearance of moderate cytoplasmic p27 expression, accompanying hypertrophy and transition of type II into type I fibers. The patients in advanced postmenopause show shrinking and fragmentation of muscle fibers associated with strong cytoplasmic p27 expression

Anti-cancer potential of synergistic phytochemical combinations is influenced by the genetic profile of prostate cancer cell lines

Introduction: Despite strong epidemiological evidence that dietary factors modulate cancer risk, cancer control through dietary intervention has been a largely intractable goal for over sixty years. The effect of tumour genotype on synergy is largely unexplored. Methods: The effect of seven dietary phytochemicals, quercetin (0–100 μM), curcumin (0–80 μM), genistein, indole-3-carbinol (I3C), equol, resveratrol and epigallocatechin gallate (EGCG) (each 0–200 μM), alone and in all paired combinations om cell viability of the androgen-responsive, pTEN-null (LNCaP), androgen-independent, pTEN-null (PC-3) or androgen-independent, pTEN-positive (DU145) prostate cancer (PCa) cell lines was determined using a high throughput alamarBlue® assay. Synergy, additivity and antagonism were modelled using Bliss additivism and highest single agent equations. Patterns of maximum synergy were identified by polygonogram analysis. Network pharmacology approaches were used to identify interactions with known PCa protein targets. Results: Synergy was observed with all combinations. In LNCaP and PC-3 cells, I3C mediated maximum synergy with five phytochemicals, while genistein was maximally synergistic with EGCG. In contrast, DU145 cells showed resveratrol-mediated maximum synergy with equol, EGCG and genistein, with I3C mediating maximum synergy with only quercetin and curcumin. Knockdown of pTEN expression in DU145 cells abrogated the synergistic effect of resveratrol without affecting the synergy profile of I3C and quercetin. Discussion: Our study identifies patterns of synergy that are dependent on tumour cell genotype and are independent of androgen signaling but are dependent on pTEN. Despite evident cell-type specificity in both maximally-synergistic combinations and the pathways that phytochemicals modulate, these combinations interact with similar prostate cancer protein targets. Here, we identify an approach that, when coupled with advanced data analysis methods, may suggest optimal dietary phytochemical combinations for individual consumption based on tumour molecular profile

Photoactivated chemotherapy (PACT) : the potential of excited-state d-block metals in medicine

The fields of phototherapy and of inorganic chemotherapy both have long histories. Inorganic photoactivated chemotherapy (PACT) offers both temporal and spatial control over drug activation and has remarkable potential for the treatment of cancer. Following photoexcitation, a number of different decay pathways (both photophysical and photochemical) are available to a metal complex. These pathways can result in radiative energy release, loss of ligands or transfer of energy to another species, such as triplet oxygen. We discuss the features which need to be considered when developing a metal-based anticancer drug, and the common mechanisms by which the current complexes are believed to operate. We then provide a comprehensive overview of PACT developments for complexes of the different d-block metals for the treatment of cancer, detailing the more established areas concerning Ti, V, Cr, Mn, Re, Fe, Ru, Os, Co, Rh, Pt, and Cu and also highlighting areas where there is potential for greater exploration. Nanoparticles (Ag, Au) and quantum dots (Cd) are also discussed for their photothermal destructive potential. We also discuss the potential held in particular by mixed-metal systems and Ru complexes