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Purpose: Impairments of hearing and auditory processing (AP) have been indicated as risk factors for dementia, but it remains unclear if persons with clinically diagnosed mild cognitive impairment (MCI) show such impairments. The objective of these analyses was to compare AP between those with and without a clinical diagnosis of MCI using a battery of AP measures., Method: Data from 274 older adults from the Keys to Staying Sharp randomized clinical trial (NCT03528486) were analyzed. A battery of AP measures in which three domains (temporal processing, binaural processing, and degraded speech understanding) were addressed by six tests was administered. Analyses were registered at https://osf.io/nga4v., Results: Those with and without a clinical diagnosis of MCI differed significantly in age, p = .002; pure-tone hearing in the left ear, p = .007; sex, p = .015; and race, p < .001. These covariates were included in multivariate analysis of covariance, which indicated significant differences between persons with and without MCI on measures of binaural processing ( p s ≤ .006), but not on measures of temporal processing or degraded speech ( p s ≥ .093). Pure-tone hearing averages did not significantly differ among those with or without MCI after adjusting for age, sex, and race ( p s ≥ .292)., Conclusions: AP in the binaural domain is impaired in MCI, but peripheral hearing did not significantly differ between those with and without MCI. Poor performance on AP measures of binaural processing may reflect problems dividing attention and may be indicative of dementia risk. Results have clinical implications for early detection of and intervention for cognitive impairment.

Background: To address the rising prevalence of Alzheimer's disease and related dementias, effective interventions that can be widely disseminated are warranted. The Preventing Alzheimer's with Cognitive Training study (PACT) investigates a commercially available computerized cognitive training program targeting improved Useful Field of View Training (UFOVT) performance. The primary goal is to test the effectiveness of UFOVT to reduce incidence of clinically defined mild cognitive impairment (MCI) or dementia with a secondary objective to examine if effects are moderated by plasma β-amyloid level or apolipoprotein E e4 (APOE e4) allele status., Methods/design: This multisite study utilizes a randomized, controlled experimental design with blinded assessors and investigators. Individuals who are 65 years of age and older are recruited from the community. Eligible participants who demonstrate intact cognitive status (Montreal Cognitive Assessment score > 25) are randomized and asked to complete 45 sessions of either a commercially available computerized-cognitive training program (UFOVT) or computerized games across 2.5 years. After three years, participants are screened for cognitive decline. For those demonstrating decline or who are part of a random subsample, a comprehensive neuropsychological assessment is completed. Those who perform below a pre-specified level are asked to complete a clinical evaluation, including an MRI, to ascertain clinical diagnosis of normal cognition, MCI, or dementia. Participants are asked to provide blood samples for analyses of Alzheimer's disease related biomarkers., Discussion: The PACT study addresses the rapidly increasing prevalence of dementia. Computerized cognitive training may provide a non-pharmaceutical option for reducing incidence of MCI or dementia to improve public health., Registration: The PACT study is registered at http://Clinicaltrials.govNCT03848312., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Edwards worked between 1996 and 2005 as a consultant conducting related research studies for Visual Awareness, Inc., who owned the intellectual property surrounding the speed of processing training software. Posit Science now markets the newest version of the training program. Over an approximate three-month period in 2008, Dr. Edwards worked as a limited consultant to Posit Science, Inc. to analyze data and prepare a publication. Dr. Edwards worked as a consultant to Wilson, Sonsini, Goodrich & Rosati across an approximate three-month period between May–August of 2015., (Published by Elsevier Inc.)

Useful Field of View (UFOV) computerized cognitive training improves older adults' gait speed and balance and reduces dementia risk. We investigated a new form of UFOV training requiring physical movement, Training Under Cognitive Kinematics (TUCK). We hypothesized TUCK would be acceptable, feasible, and potentially efficacious to improve UFOV Test- and motor performance. Sixty-nine older adults were randomized to TUCK, computerized UFOV training, or an active control group. Cognitive- and motor function were assessed before and immediately after the intervention period. Participants rated TUCK as enjoyable, engaging and satisfying, indicating acceptability. Eighty-five percent of participants completed TUCK, demonstrating feasibility. Overall, effect sizes for TUCK did not indicate greater efficacy than computerized UFOV training relative to controls. UFOV training showed effect sizes indicating improved balance as measured by Turn 360 ( d =0.37) and Optogait ( d =0.51-0.69) from pre- to post- training relative to controls. Incorporating movement into UFOV cognitive training did not enhance cognitive or motor functional gains. Future investigations are needed to elucidate the underlying mechanisms of UFOV cognitive training to enhance motor function. Research should continue to investigate the association of cognitive and motor function and interventions to improve these outcomes among older adults. The trial and planned analyses were pre-registered: https://osf.io/7utgw.

[Figure: see text].

Despite the demonstrated benefits of computerized cognitive training for older adults, little is known about the determinants of training behavior. We developed and tested scales to quantify expectations about such training, examine whether expectations predicted training adherence, and explore if training expectations changed from pre- to post-training. Participants ( N =219) were healthy older adults aged 55-96 years ( M =75.36, SD =9.39), enrolled in four studies investigating Dakim, Insight, or Posit Science Brain Fitness computerized cognitive training programs. Instruments were adapted from existing health behavior scales: Self Efficacy for Cognitive Training, Outcome Expectations for Cognitive Training, Perceived Susceptibility to Cognitive Decline, Dementia or Alzheimer's Disease, and Perceived Severity of Cognitive Decline, Dementia or Alzheimer's Disease. Participants completed scales at baseline ( N =219) and post-training ( n =173). Eight composites were derived from factor analyses. Adherence rates were high ( M =81%), but none of the composites predicted training adherence. There was an overall significant effect of time, Wilks' λ=.843, F (8, 114)=2.65, p =.010, partial η 2 =.157, a significant overall effect of training group, Wilks' λ=.770, F (16, 228)=1.99, p =.015, partial η 2 =.123, and an overall significant group x time interaction, Wilks' λ=.728, F (16, 226)=2.44, p =.002, partial η 2 =.147. Significant effects of time were found for e xpected psychological outcomes and self-efficacy . Post-training, participants more strongly agreed that training was enjoyable and increased their sense of accomplishment. Changes in s elf-efficacy for cognitive training varied by program, improvingfor Dakim- and declining for the more challenging Brain Fitness- and InSight participants. These newly devised scales may be useful for examining cognitive training behaviors. However, more work is needed to understand factors that influence older adults' enrollment in and adherence to cognitive training., Competing Interests: Conflicts of Interest: Over an approximate three-month period in 2008, Dr. Edwards worked as a limited consultant to analyze data and prepare a publication for Posit Science, Inc., who marketed the InSight and Brain Fitness programs. Dr. Edwards served on the data safety and monitoring board of NIH grants awarded to employees of Posit Science from 2016–2018.

Background: Evidence on effective engagement of diverse participants in AD prevention research is lacking., Objectives: To quantify recruitment source in relation to race, ethnicity, and retention., Design: Prospective cohort study., Setting: University lab., Participants: Participants included older adults (N=1170) who identified as White (86%), Black (8%), and Hispanic/Latino ethnicity (6%)., Measurements: The Cognitive Aging Lab Marketing Questionnaire assessed recruitment source, social media use, and research opportunity communication preferences., Results: Effective recruitment methods and communication preferences vary by race and ethnicity. The most common referral sources were postcards for racial minorities, friend/family referrals for Hispanic/Latinos, and the newspaper for Whites. Whereas Whites preferred email communications, Hispanic/Latinos preferred texts., Conclusions: Recruiting diverse samples in AD prevention research is clinically relevant given high AD-risk of minorities and that health disparities are propagated by their under-representation in research. Our questionnaire and these results may be applied to facilitate effective research engagement., Competing Interests: The authors declare that they have no conflicts of interest.

Background: The prevalence of dementia, the most expensive medical condition (Kirschstein, 2000 and Hurd et al., 2013 [1,2]), and its precursor, mild cognitive impairment (MCI) are increasing [3]. Finding effective intervention strategies to prevent or delay dementia is imperative to public health. Prior research provides compelling evidence that central auditory processing (CAP) deficits are a risk factor for dementia [4-6]. Grounded in the information degradation theory [7, 8], we hypothesize that improving brain function at early perceptual levels (i.e., CAP) may be optimal to attenuate cognitive and functional decline and potentially curb dementia prevalence. Piano training is one avenue to enhance cognition [9-13] by facilitating CAP at initial perceptual stages [14-18]., Objectives: The Keys To Staying Sharp study is a two arm, randomized clinical trial examining the efficacy of piano training relative to music listening instruction to improve CAP, cognition, and everyday function among older adults. In addition, the moderating effects of MCI status on piano training efficacy will be examined and potential mediators of intervention effects will be explored., Hypotheses: We hypothesize that piano training will improve CAP and cognitive performance, leading to functional improvements. We expect that enhanced CAP will mediate cognitive gains. We further hypothesize that cognitive gains will mediate functional improvements., Method: We plan to enroll 360 adults aged 60 years and older who will be randomized to piano training or an active control condition of music listening instruction and complete pre- and immediate post- assessments of CAP, cognition, and everyday function., (Copyright © 2019. Published by Elsevier Inc.)

Objective: Charge injection through platinum neural stimulation electrodes is often constrained by the Shannon limit (Shannon 1992 IEEE Trans. Biomed. Eng. 39 424-6) of k  =  1.75. By leveraging the tools of electrochemistry to better understand the reactions at electrode-tissue interface, we endeavor to find a way to safely inject more charge than allowed if the traditional Shannon limit were followed., Approach: In previous studies on platinum electrodes using charge-balanced, cathodic-first, biphasic pulses, we noted that during the secondary anodic phase, the electrode potential moves into a range where platinum dissolution is possible when charge injection is greater than k  =  1.75. Platinum dissolution products are known to be toxic to brain tissues. We hypothesize that by injecting less charge in the anodic phase than the cathodic phase, the anodic potential excursions will decrease, thereby avoiding potentials where platinum dissolution is more likely., Main Results: Our findings show that using these charge-imbalanced pulses decreases the anodic potential excursions to a level where platinum oxidation and dissolution are less likely, and aligns the anodic potentials with those observed with charge-balanced stimulation at k  <  1.75-a range widely accepted as safe for stimulation with platinum., Significance: From these results, we further hypothesize that charge-imbalanced biphasic stimulation would permit more charge to be safely injected through platinum electrodes than would be permitted if the dogma of charge-balanced biphasic stimuli were followed. Testing this hypothesis in cat brain in the same manner as the experiments that formed the basis for the Shannon plot could open the door for safe charge injection through platinum electrodes at levels greater than k  =  1.75.

Objective: The Shannon model is often used to define an expected boundary between non-damaging and damaging modes of electrical neurostimulation. Numerous preclinical studies have been performed by manufacturers of neuromodulation devices using different animal models and a broad range of stimulation parameters while developing devices for clinical use. These studies are mostly absent from peer-reviewed literature, which may lead to this information being overlooked by the scientific community. We aimed to locate summaries of these studies accessible via public regulatory databases and to add them to a body of knowledge available to a broad scientific community., Methods: We employed web search terms describing device type, intended use, neural target, therapeutic application, company name, and submission number to identify summaries for premarket approval (PMA) devices and 510(k) devices. We filtered these records to a subset of entries that have sufficient technical information relevant to safety of neurostimulation., Results: We identified 13 product codes for 8 types of neuromodulation devices. These led us to devices that have 22 PMAs and 154 510(k)s and six transcripts of public panel meetings. We found one PMA for a brain, peripheral nerve, and spinal cord stimulator and five 510(k) spinal cord stimulators with enough information to plot in Shannon coordinates of charge and charge density per phase., Conclusions: Analysis of relevant entries from public regulatory databases reveals use of pig, sheep, monkey, dog, and goat animal models with deep brain, peripheral nerve, muscle and spinal cord electrode placement with a variety of stimulation durations (hours to years); frequencies (10-10,000 Hz) and magnitudes (Shannon k from below zero to 4.47). Data from located entries indicate that a feline cortical model that employs acute stimulation might have limitations for assessing tissue damage in diverse anatomical locations, particularly for peripheral nerve and spinal cord simulation., (© 2017 International Neuromodulation Society.)

Objective: Our mission is twofold: (1) find a way to safely inject more charge through platinum electrodes than the Shannon limit (k  =  1.75) permits and (2) nurture an interest in the neural stimulation community to understand the electron transfer process occurring on neural stimulating electrodes., Approach: We report here on measurements of the electrode potential, performed on platinum neural stimulating electrodes in the subcutaneous space of an anesthetized rat under neural stimulation conditions., Main Results: The results for six platinum electrodes with areas ranging from 0.2 mm 2 to 12.7 mm 2 were similar to prior results in sulfuric acid, except that the measured potentials were shifted negative 0.36 V because of the pH difference between the two media. The anodic 'end' potential, measured at t  =  20 ms after the onset of the biphasic current pulse, was the primary focus of the data collected because previous results had shown that as charge injection crosses the Shannon limit (k  =  1.75), this potential moves into a range where platinum surface oxidation and dissolution is likely to occur. The behavior of V e (t  =  20 ms) over a range of electrode surface areas studied was consistent with our sulfuric acid study. Implicit, but little noticed, in Shannon's formulation is that small and large platinum electrodes behave the same in terms of k value; our data supports this idea., Significance: We hypothesize that the k  =  1.75 Shannon limit for safe stimulation designates a charge-injection boundary above which platinum toxicity becomes a relevant consideration for living cells around an electrode, a possibility that can be directly tested, and is a vital step forward in mission (1).

High-throughput screening (HTS) is a widespread method in early drug discovery for identifying promising chemical matter that modulates a target or phenotype of interest. Because HTS campaigns involve screening millions of compounds, it is often desirable to initiate screening with a subset of the full collection. Subsequently, virtual screening methods prioritize likely active compounds in the remaining collection in an iterative process. With this approach, orthogonal virtual screening methods are often applied, necessitating the prioritization of hits from different approaches. Here, we introduce a novel method of fusing these prioritizations and benchmark it prospectively on 17 screening campaigns using virtual screening methods in three descriptor spaces. We found that the fusion approach retrieves 15% to 65% more active chemical series than any single machine-learning method and that appropriately weighting contributions of similarity and machine-learning scoring techniques can increase enrichment by 1% to 19%. We also use fusion scoring to evaluate the tradeoff between screening more chemical matter initially in lieu of replicate samples to prevent false-positives and find that the former option leads to the retrieval of more active chemical series. These results represent guidelines that can increase the rate of identification of promising active compounds in future iterative screens.

Objective: Neural prostheses employing platinum electrodes are often constrained by a charge/charge-density parameter known as the Shannon limit. In examining the relationship between charge injection and observed tissue damage, the electrochemistry at the electrode-tissue interface should be considered. The charge-storage capacity (CSC) is often used as a predictor of how much charge an electrode can inject during stimulation, but calculating charge from a steady-state i-E curve (cyclic voltammogram) over the water window misrepresents how electrodes operate during stimulation. We aim to gain insight into why CSC predictions from classic i-E curves overestimate the amount of charge that can be injected during neural stimulation pulsing., Approach: In this study, we use a standard electrochemical technique to investigate how platinum electrochemistry depends on the potentials accessed by the electrode and on the electrolyte composition., Main Results: The experiments indicate: (1) platinum electrodes must be subjected to a 'cleaning' procedure in order to expose the maximum number of surface platinum sites for hydrogen adsorption; (2) the 'cleaned' platinum surface will likely revert to an obstructed condition under typical neural stimulation conditions; (3) irreversible oxygen reduction may occur under neural stimulation conditions, so the consequences of this reaction should be considered; and (4) the presence of the chloride ion (Cl - ) or proteins (bovine serum albumin) inhibits oxide formation and alters H adsorption., Significance: These observations help explain why traditional CSC calculations overestimate the charge that can be injected during neural stimulation. The results underscore how careful electrochemical examination of the electrode-electrolyte interface can result in more accurate expectations of electrode performance during applied stimulation.

Background: It is currently unclear how the platinum (Pt) species released from platinum-containing stimulating electrodes may affect the health of the surrounding tissue. This study develops an effective system to assess the cytotoxicity of any electrode-liberated Pt over a short duration, to screen systems before future in vivo testing., New Method: A platinum electrode was stimulated for two hours under physiologically relevant conditions to induce the liberation of Pt species. The total concentration of liberated Pt species was quantified and the concentration found was used to develop a range of Pt species for our model system comprised of microglia and neuron-like cells., Results: Under our stimulation conditions (k=2.3, charge density of 57.7μC/cm 2 ), Pt was liberated to a concentration of 1ppm. Interestingly, after 24h of Pt exposure, the dose-dependent cytotoxicity plots revealed that cell death became statistically significant at 10ppm for microglia and 20ppm for neuronal cells. However, in neuron-like cell cultures, concentrations above 1ppm resulted in significant neurite loss after 24h., Comparison With Existing Methods: To our knowledge, there does not exist a simple, in vitro assay system for assessing the cytotoxicity of Pt liberated from stimulating neural electrodes., Conclusions: This work describes a simple model assay that is designed to be applicable to almost any electrode and stimulation system where the electrode is directly juxtaposed to the neural target. Based on the application, the duration of stimulation and Pt exposure may be varied., (Published by Elsevier B.V.)

Objective: Electrical neurostimulation has traditionally been limited to the use of charge-balanced waveforms. Charge-imbalanced and monophasic waveforms are not used to deliver clinical therapy, because it is believed that these stimulation paradigms may generate noxious electrochemical species that cause tissue damage., Approach: In this study, we investigated the dissolution of platinum as one of such irreversible reactions over a range of charge densities up to 160 μC cm -2 with current-controlled first phase, capacitive discharge second phase waveforms of both cathodic-first and anodic-first polarity. We monitored the concentration of platinum in solution under different stimulation delivery conditions including charge-balanced, charge-imbalanced, and monophasic pulses., Main Results: We observed that platinum dissolution decreased during charge-imbalanced and monophasic stimulation when compared to charge-balanced waveforms., Significance: This observation provides an opportunity to re-evaluate the charge-balanced waveform as the primary option for sustainable neural stimulation.

The aim of this tutorial is to encourage members of the neuroprosthesis community to incorporate electron transfer processes into their thinking and provide them with the tools to do so when they design and work with neurostimulating devices. The focus of this article is on platinum because it is the most used electrode metal for devices in commercial use. The i(V e) profile or cyclic voltammogram contains information about electron transfer processes that can occur when the electrode-electrolyte interface, V e, is at a specific potential, and assumed to be near steady-state conditions. For the engineer/designer this means that if the potential is not in the range of a specific electron transfer process, that process cannot occur. An i(V e) profile, recorded at sweep rates greater than 0.1 mVs(-1), approximates steady-state conditions. Rapid transient potential excursions, like that seen with neural stimulation pulses, may be too fast for the reaction to occur, however, this means that if the potential is in the range of a specific electron transfer process it may occur and should be considered. The approach described here can be used to describe the thermodynamic electron transfer processes on other candidate electrode metals, e.g. stainless steel, iridium, carbon-based, etc.

The application of a train of cathodic-first/charge-balanced/biphasic pulses applied to a platinum electrode resulted in a positive creep of the anodic phase potential that increases with increasing charge injection but reaches a steady-state value before 1000 pulses have been delivered. The increase follows from the fact that charge going into irreversible reactions occurring during the anodic phase must equal the charge going into irreversible reactions during the cathodic phase for charge-balanced pulses. In an oxygenated electrolyte the drift of the measured positive potential moved into the platinum oxidation region of the i(V e) profile when the charge injection level exceeds k = 1.75. Platinum dissolution may occur in this region and k = 1.75 defines a boundary between damaging and non-damaging levels on the Shannon Plot. In a very low oxygen environment, the positive potential remained below the platinum oxidation region for the highest charge injection values studied, k = 2.3. The results support the hypothesis that platinum dissolution is the defining factor for the Shannon limit, k = 1.75. Numerous instrumentation issues were encountered in the course of making measurements. The solutions to these issues are provided.

Introduction: The safety and effectiveness of outpatient endoscopic minimally invasive spinal surgery (MISS) for the treatment of lumbar spinal stenosis among obese patients is not well documented., Methods: Pain, disability, and surgical variables were examined on 41 adult obese patients that underwent lumbar laminotomy and foraminotomy surgeries., Results: A significant decrease in pain and disability scores between preoperative and postoperative were found (p-value's < 0.001)., Discussion: MISS using endoscopy can achieve sufficient decompression that results in a significant reduction in the level of pain and disability among obese patients with minimal blood loss and no complications.

Objective: The present study examined health and physical performance as mediators of the association between driving cessation and mortality among older residents of small and large cities., Method: Participants (N = 2,793) were from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study. Participants' driving status and health were measured at baseline, and mortality rates were observed across the subsequent 5 years., Results: Overall, mortality risk was 1.68 times higher for nondrivers versus drivers; this relationship was significantly mediated by physical performance and social, physical, and general health. For large-city residents, mediation effects for all mediators were significant and complete. For small-city residents, only physical and general health were significant mediators, and these effects were partial., Discussion: Health difficulties that accompany or follow driving cessation may explain the association between driving cessation and mortality, particularly for residents of large cities, where alternative transportation options may be more numerous.

Background: Lumbar spinal stenosis is a common cause of radicular and generalized back pain among older adults. Endoscopic minimally invasive surgery, in contrast to open decompression, may provide the opportunity for a less invasive surgical intervention. Thus, the purpose of this study is to evaluate the safety (operative complications, estimated blood loss, operative room time) and effectiveness (pre- versus postoperative level of disability and pain severity) of minimally invasive surgery using endoscopic laminotomy and foraminotomy among a large sample of patients with lumbar spinal stenosis., Methods: This study is composed of 320 consecutive patients with lumbar spinal stenosis who underwent posterior lumbar laminotomy and foraminotomy between 2008 and 2011. Outcome measures consisted of perioperative complications, estimated blood loss, operative room time, level of disability, and pain severity. Pain severity and level of disability were prospectively analyzed to an average of 18 months (12-36 months) post-surgery., Results: There was an average estimated blood loss of 39.3 cc and a mean operative room time of 74 min. Seven patients experienced minor operative complications. All patients were discharged the same day as surgery and reported a significantly lower level of disability (p = 0.00) and pain severity (p = 0.00) postoperative compared to preoperative., Conclusions: Minimally invasive surgery using endoscopy for the treatment of lumbar spinal stenosis has a short operative time, a low operative complication rate, and minimal estimated blood loss. This study also indicates that MIS for the treatment of LSS can significantly reduce pain and disability level. Thus, minimally invasive surgery using endoscopic laminotomy and foraminotomy appears to be a safe and effective alternative surgical treatment for open decompression surgery in adult patients with lumbar spinal stenosis.

Secondary data analyses examined the differences in cognitive and instrumental activities of daily living (IADL) performance among hypertensive individuals taking one of four classes of antihypertensive medications, hypertensive individuals not taking any antihypertensive medications, and normotensive individuals (N=770). After adjusting for covariates, significant group differences were evident on all measures (speed of processing, motor speed, reaction time, p s < .05) except memory and Timed IADL ( p s > .05). Follow-up a priori planned comparisons compared hypertensive individuals not on medications to each of the four antihypertensive medication groups. Results indicated that only those on beta blockers (BB) were significantly slower in speed of processing (ps < .05). A priori planned comparisons also revealed that normotensive individuals had better cognitive performance on measures of processing speed, motor speed, and reaction time than hypertensive individuals regardless of antihypertensive medication use. Additionally, normotensive individuals performed significantly better on memory (Digit and Spatial Span) than individuals with hypertension on medications. No differences were found between groups on memory (Hopkins Verbal Learning Test) or Timed IADL performance. With regard to antihypertensive medications, the use of BBs was associated with slowed processing speed. These analyses provide empirical evidence that hypertension primarily impacts speed of processing, but not severe enough to affect IADL performance. Given the contribution of processing speed to memory and executive function performance, this is an important finding. Clinicians need to take into consideration the potential negative impact that BBs may have on cognition when determining the best treatment of hypertension among older adult patients.

Combination therapies that enhance efficacy or permit reduced dosages to be administered have seen great success in a variety of therapeutic applications. More fundamentally, the discovery of epistatic pathway interactions not only informs pharmacologic intervention but can be used to better understand the underlying biological system. There is, however, no systematic and efficient method to identify interacting activities as candidates for combination therapy and, in particular, to identify those with synergistic activities. We devised a pooled, self-deconvoluting screening paradigm for the efficient comprehensive interrogation of all pairs of compounds in 1000-compound libraries. We demonstrate the power of the method to recover established synergistic interactions between compounds. We then applied this approach to a cell-based screen for anti-inflammatory activities using an assay for lipopolysaccharide/interferon-induced acute phase response of a monocytic cell line. The described method, which is >20 times as efficient as a naïve approach, was used to test all pairs of 1027 bioactive compounds for interleukin-6 suppression, yielding 11 pairs of compounds that show synergy. These 11 pairs all represent the same two activities: β-adrenergic receptor agonists and phosphodiesterase-4 inhibitors. These activities both act through cyclic AMP elevation and are known to be anti-inflammatory alone and to synergize in combination. Thus we show proof of concept for a robust, efficient technique for the identification of synergistic combinations. Such a tool can enable qualitatively new scales of pharmacological research and chemical genetics.

Background. Community mobility is crucial for maintaining independent functioning and quality of life for older adults. Purpose. The present paper describes the relationship of cognition, particularly speed of processing as measured by the Useful Field of View Test, to mobility as indicated by driving behaviors, life space, and falls among healthy older adults. Research examining the impact of cognitive speed of processing training (SOPT) on older adults' community mobility (i.e., driving behaviors) is also summarized. Key Issues. Even slight cognitive declines can place older adults at risk for mobility limitations. However, cognitive interventions like SOPT can mitigate declines in driving mobility. Implications. The potential of SOPT to sustain community mobility among older adults is discussed.

The underlying cause of electrical stimulation-induced tissue trauma is debated. Our focus has been to study effects of generating electrochemical by-products at the electrode-electrolyte interface, using the pulse-clamp technique coupled with voltammetry to analyze charge transfer. The platinum-H(2)SO(4) system has been a standard for analyzing electrochemistry on platinum-stimulating electrodes, even though the chemical differences between H(2)SO(4) and the living body are obvious. Experiments were designed to determine whether phosphate-buffered saline (PBS) could serve as a more accurate emulation of living tissue. It had been rumored that platinum's performance in PBS deviates from that in H(2)SO(4) at larger potentials. Voltammetry in PBS was performed in two potential ranges. In a conventional potential range (-0.6 V to +0.9 V versus Ag/AgCl), characteristic peaks appear very similar to published voltammograms of platinum in H(2)SO(4). However, in an extended range (-1.0 V to +1.7 V versus Ag/AgCl), platinum exhibited additional electrochemical activity: one oxidation peak and two reduction peaks. Therefore, voltammetry was performed in NaCl and a sodium phosphate mixture (i.e. PBS components) to separate their activity. The altered electrochemical performance of platinum in PBS suggests that certain reactions on platinum at potentials outside the water window will not reflect what happens in vivo.