Adverse childhood experiences and psychotropic medication prescription among cancer patients.

BACKGROUND: This study aimed at identifying and characterizing adverse childhood experiences (ACEs) in a sample of cancer patients and subsequently evaluating the relationship between ACEs and prescription of psychotropic medication among them. Individuals with ACEs have a higher risk of mental health conditions and are more likely to be prescribed psychotropic medications. METHODS: A sample of 178 adult patients receiving Supportive Oncology & Survivorship (SOS) services at Huntsman Cancer Hospital in Utah was obtained. ACEs and Brief Resilient Coping Scale (BRCS) questionnaires were administered confidentially. A multivariable mixed effect model, adjusting for sex, age, and insurance type while controlling for zip-codes clustering were employed. RESULTS: Compared to the prevalence of ACEs in the general population, from the CDC-Kaiser Permanente ACEs Study, we found no significant difference in the prevalence of people who had experienced an adverse childhood event (ACEs score > = 1) between our study of cancer patients and the CDC-Kaiser study (67.4% vs. 63.6%, p = 0.29372), but found a significant difference in the prevalence of people who had experienced severe adverse childhood experiences (ACES score > =4) (25.3% vs. 12.1%, p < 0.00001). Furthermore, this study reveals a significant association between an increase of one unit in the total ACEs score and the odds of psychotropic medication prescription in the past 12 months (OR: 1.233; 95% CI: 1.025, 1.483). Those with a total ACEs score of three or more were found to have 280% higher odds of being prescribed psychotropic medication compared to those with ACEs ≤ 2 (OR: 3.822; 95% CI: 1.404,10.407). CONCLUSION: A significant proportion of cancer patients have a history of ACEs, and thus trauma-informed care approach is essential during their treatment.

Non-steroidal anti-inflammatory drug use and markers of Parkinson's disease progression: A retrospective cohort study.

BACKGROUND: Previous studies demonstrated reduced incidence of Parkinson's disease (PD) with regular non-steroidal anti-inflammatory drug (NSAID) exposure, particularly ibuprofen. No studies have investigated the impact of NSAID exposure on markers of disease progression for established PD. METHODS: This is a retrospective observational study using two cohorts. The Deprenyl and Tocopheral Anti-Oxidative Therapy of Parkinsonism (DATATOP) study enrolled 800 drug naïve people with PD with a median follow-up duration of 6.5 years. The DATATOP primary outcome measures were mortality at last study visit. The Parkinson's Progression Markers Initiative (PPMI) cohort was limited to drug naïve PD participants (423 at time of analysis). The PPMI primary outcome measure was annual rate of change in ipsilateral putamen 123I-ioflupane binding ratio at four years study duration. Regular NSAID exposure was defined as any scheduled NSAID use (as needed use was excluded). Analysis was performed separately for recent exposure and cumulative exposure time (CET). RESULTS: Total CET median and interquartile range (years) for ibuprofen, non-aspirin NSAID, and aspirin were respectively 0.9 (0.3-2.9), 1.1 (0.3-2.6), and 1.5 (0.4-2.8) for DATATOP and 0.4 (0.01-2.2), 1.4 (0.3-4.4), and 5.5 (2.6-7.1) for PPMI. Exposure was usually discontinuous. Exposure to ibuprofen was low in both cohorts. There was no significant association between NSAID recent exposure or CET and primary outcome measures in either cohort. CONCLUSIONS: NSAID exposure in established PD does not appear to provide protective effect although exposure may not have occurred continuously enough in these two cohorts to provide benefit. Statistical power for ibuprofen exposure analyses was limited.

Predictors of Cognitive Change in Parkinson Disease: A 2-year Follow-up Study.

BACKGROUND: Mild cognitive impairment is common in Parkinson disease (PD-MCI). However, instability in this clinical diagnosis and variability in rates of progression to dementia raises questions regarding its utility for longitudinal tracking and prediction of cognitive change in PD. We examined baseline neuropsychological test and cognitive diagnosis predictors of cognitive change in PD. METHODS: Persons with PD, without dementia PD (N=138) underwent comprehensive neuropsychological assessment at baseline and were followed up to 2 years. Level II Movement Disorder Society criteria for PD-MCI and PD dementia (PDD) were applied annually. Composite global and domain cognitive z -scores were calculated based on a 10-test neuropsychological battery. RESULTS: Baseline diagnosis of PD-MCI was not associated with a change in global cognitive z -scores. Lower baseline attention and higher executive domain z -scores were associated with greater global cognitive z -score worsening regardless of cognitive diagnosis. Worse baseline domain z -scores in the attention and language domains were associated with progression to MCI or PDD, whereas higher baseline scores in all cognitive domains except executive function were associated with clinical and psychometric reversion to "normal" cognition. CONCLUSIONS: Lower scores on cognitive tests of attention were predictive of worse global cognition over 2 years of follow-up in PD, and lower baseline attention and language scores were associated with progression to MCI or PDD. However, PD-MCI diagnosis per se was not predictive of cognitive decline over 2 years. The association between higher executive domain z -scores and greater global cognitive worsening is probably a spurious result.

Parkinson disease with mild cognitive impairment: Domain-specific cognitive complaints predict dementia.

BACKGROUND: The presence of subjective cognitive complaints (SCC) as a predictor of cognitive impairment in Parkinson´s disease (PD) has shown conflicting results. Most previous studies only assessed complaints in the memory domain. We investigate the association of SCCs across cognitive domains with development of mild cognitive impairment (PD-MCI) and dementia (PDD) in PD and to assess agreement between SCCs and objective cognitive impairments in this population. METHODS: This is a retrospective analysis of a prospective cohort study. Participants were enrolled at six North-American movement disorders centers. They underwent neuropsychological and non-cognitive clinical evaluations, including the modified Neurobehavioral Inventory to elicit SCC (rated by each patient and independently by their close contact (CC)). Associations between SCCs and development of future cognitive impairment were assessed. Agreement between SCCs and objective impairment within the same domain was also calculated. RESULTS: Of 138 included PD patients, 42% fulfilled criteria for PD-MCI. None of the NBI items predicted development of cognitive impairment after one and two years in PD with normal cognition. In PD-MCI patients, SCCs related to attention predicted dementia at year one. CC ratings of SCCs related to memory and language problems predicted PDD in PD-MCI patients. According to CC reported patients' complaints, there was a significant agreement between SCCs and objective cognitive test scores on attention. CONCLUSIONS: Eliciting SCCs including cognitive domains other than memory is crucial for a complete evaluation, including both patient and CC report. Memory, language, and especially attention SCCs in PD-MCI may predict progression to dementia.

Responsiveness to Change of the Montreal Cognitive Assessment, Mini-Mental State Examination, and SCOPA-Cog in Non-Demented Patients with Parkinson's Disease.

BACKGROUND: Clinical monitoring of patients with Parkinson's disease (PD) for cognitive decline is an important element of care. The Montreal Cognitive Assessment (MoCA) has been proposed to be a sensitive tool for assessing cognitive impairment in PD. The aim of our study was to compare the responsiveness of the MoCA to decline in cognition to the responsiveness of the Mini Mental State Examination (MMSE) and the Scales for Outcomes of Parkinson's disease-cognition (SCOPA-Cog). METHODS: PD patients without dementia were enrolled at 6 North American movement disorders centers between 2008 and 2011. Participants received annual evaluations including the MoCA, MMSE, and SCOPA-Cog followed by formal neuropsychological testing. The gold standard for change in cognition was defined as the change on the neuropsychological test scores over the annual assessments. The Reliable Change Method was used to provide an estimate of the probability that a given difference score would be obtained by chance. The sensitivity of the MoCA, MMSE, and SCOPA-Cog to change was quantified using receiver operating characteristics (ROC) curves. RESULTS: One hundred seventeen patients were included in the analysis. Participants were followed at mean intervals of 11 ± 2 months for a median of 2 (maximum 5) visits. According to the reliable change index, 56 intervals of cognitive testing showed a decline in global cognition. ROC analysis of change in MoCA, MMSE, and SCOPA-Cog global scores compared to gold standard testing found an area under the curve (AUC) of 0.55 (95% CI 0.48-0.62), 0.56 (0.48-0.63), and 0.63 (0.55-0.70) respectively. There were no significant differences in the AUCs across the tests. The sensitivity of the MoCA, MMSE, and SCOPA-Cog to change at various thresholds for decline in scores reached a maximum of 71% for a cut-off of 1 point change on the SCOPA-Cog. CONCLUSION: Using neuropsychological testing as a gold standard comparator, the performance of the MoCA, MMSE, and SCOPA-Cog for detecting decline in non-demented PD patients over a 1-year interval is poor. This has implications for clinical practice; stable scores may not be taken as reassurance of the absence of cognitive decline.

Cognitive Complaints in Nondemented Parkinson's Disease Patients and Their Close Contacts do not Predict Worse Cognitive Outcome.

OBJECTIVES: The main purpose of this study was to investigate 4 methods of eliciting subjective cognitive complaints (SCCs) in Parkinson's disease (PD) patients without dementia and determine the relationship between their SCC and cognitive performance. DESIGN: This study was a retrospective analysis of a prospective cohort study. SETTING: Six North American movement disorder clinics. MEASUREMENTS: SCCs were elicited through a modified Neurobehavioral Inventory administered to patients and close contacts, a general complaint question, and Movement Disorders Society Unified Parkinson's Disease Rating Scale item question 1.1 administered to patients. Clinical evaluation, formal neuropsychological testing and Disability Assessment for Dementia were conducted in Ontario state. Agreement between SCCs eliciting methods was calculated. Associations between SCC, cognitive testing, and mild cognitive impairment (MCI) were assessed. RESULTS: Of 139 participating nondemented PD patients, 42% had PD-MCI at baseline. Agreement between SCC eliciting methods was low. Neither patient-reported nor close contact-reported SCCs were associated with impaired baseline cognitive testing or PD-MCI nor were they associated with cognitive decline over time. In PD patients with normal baseline cognition, 26% of patients with 1-year follow-up and 20% of patients with 2-year follow-up met MCI criteria. CONCLUSIONS: Agreement between SCC eliciting methods is poor and no SCC method was associated with cognitive testing or decline over time. With no clear superior method for eliciting SCCs, clinicians should consider performing regular screening.

Spin-echo small-angle neutron scattering (SESANS) studies of diblock copolymer nanoparticles.

Poly(glycerol monomethacrylate)-poly(benzyl methacrylate) (PGMA-PBzMA) diblock copolymer nanoparticles were synthesized via polymerization-induced self-assembly (PISA) using reversible addition-fragmentation chain-transfer (RAFT) aqueous emulsion polymerization in D2O. Such PISA syntheses produce sterically-stabilized nanoparticles in situ and can be performed at relatively high copolymer concentrations (up to 50 wt%). This PGMA-PBzMA formulation is known to form only spherical nanoparticles in water using aqueous emulsion polymerization (Macromolecules, 2014, 47, 5613-5623), which makes it an ideal model system for exploring new characterization methods. The polymer micelles were characterized using small-angle X-ray scattering (SAXS) and a recently developed form of neutron scattering, spin-echo small-angle neutron scattering (SESANS). As far as we are aware, this is the first report of a study of polymer micelles by SESANS, and the data agree well with reciprocal-space scattering. Using this technique enables characterization of the concentrated, as synthesized dispersions directly without dilution, and this will provide a method to study self-assembled polymer systems that have concentration dependent morphologies, while still maintaining the advantages of scattering techniques.

Effect of Topical Anesthetic Cream on Pain During Periareolar Injection of Technetium Tc99m Sulfur Colloid for Sentinel Lymph Node Biopsy in Breast Cancer: A Randomized Control Trial.

BACKGROUND: Injection of Tc99m to localize nodes for sentinel lymph node biopsy is reported by patients as very painful. The purpose of this study was to determine if anesthetic cream reduces pain associated with periareolar injection of Tc99m and to help elucidate conflicting literature regarding the efficacy of anesthetic cream for this procedure. METHODS: A randomized, double-blind, placebo-controlled methodology was used for adult females with breast cancer undergoing periareolar injection of Tc99m for sentinel lymph node biopsy. Pain levels were compared using anesthetic cream (2.5% lidocaine/2.5% prilocaine) vs. placebo. Patient exclusion criteria included use of opioids or adjuvant pain medication or injecting Tc99m the day before surgery. The Numerical Rating Scale was used to assess pain levels immediately after the injections. RESULTS: Comparing 23 experimental and 26 control patients, there was no significant difference between the experimental (median = 4) and the control group (median = 5) on level of pain experienced U= 0.492, P > .05. CONCLUSIONS: The experimental group had a slightly lower median pain score; however, there was no statistically significant difference between those who used the cream compared with those who used a placebo, supporting the conclusion that anesthetic cream does not reduce pain during Tc99m injections. This study adds to the current literature to provide a stronger position that there is no benefit to using anesthetic cream for this procedure.

Brain tissue pulsatility is related to clinical features of Parkinson's disease.

Introduction: This study investigated whether brain tissue pulsatility is associated with features of disease severity in Parkinson's disease (PD). Methods: Data were extracted from the Parkinson's Progression Markers Initiative among 81 adults with PD (confirmed with DATSCAN™). Brain tissue pulsatility was computed using resting state blood oxygenation level dependent (BOLD) MRI in white matter (WM), referred to as BOLDTP. Motor impairment was assessed using the Movement Disorders Society unified Parkinson's disease rating scale. Factor analysis generated composite scores for cognition and vascular risk burden. A linear regression model examined the association of BOLDTP with age, sex, motor impairment, cognition, vascular risk burden and PD duration. In addition, we investigated whether BOLDTP relates to WM hyperintensity (WMH) volume, WM fractional anisotropy (WM-FA) and striatal binding ratio (SBR) of dopamine transporter. Results: Motor impairment (t = 2.3, p = .02), vascular burden (t = 2.4, p = .02) and male sex (t = 3.0, p = .003) were independently associated with BOLDTP (r2 = 0.40, p < .001). BOLDTP was correlated with WMH volume (r = 0.22, p = .05) but not WM-FA nor SBR (p > .1). In addition, BOLDTP (t = 2.76, p = .008) and SBR (t = -2.04, p = .04) were independently related to motor impairment (r2 = 0.18, p = .006). Conclusion: Our findings show that brain tissue pulsatility from BOLD images in WM is related to neurological and vascular features in PD. BOLDTP may be useful in PD to study small vessel alterations that appear distinct from WM structural changes.

Impact of Androgen Deprivation Therapy on Self-Reported Cognitive Function in Men with Prostate Cancer.

PURPOSE: Although androgen deprivation therapy is widely used to treat prostate cancer, its effects on cognitive function are unclear. To our knowledge no prior report has examined the impact of androgen deprivation therapy on self-reported cognitive function. MATERIALS AND METHODS: Three groups of men 50 years old or older who were matched on age and education were enrolled in the study, including 81 with prostate cancer starting on continuous androgen deprivation therapy, 84 controls with prostate cancer not receiving androgen deprivation therapy and 85 healthy controls. Two scales from the FACT-Cog (Functional Assessment of Cancer Therapy-Cognitive subscale) version 3 were used to assess self-reported cognitive function. Changes in cognitive scores with time were analyzed by 2 approaches, including 1) multivariable regression and 2) calculation of the proportion of subjects per group with a decrease of 1 SD or more. Multivariable regression was applied to assess predictors of a decline in self-reported cognitive function. We also examined relationships between the FACT-Cog and a neuropsychological battery of 15 tests. RESULTS: Mean participant age was 69 years (range 50 to 87). The mean educational level was 15 years (range 8 to 24). FACT-Cog scores were similar at baseline across the cohorts. Neither analytical approach revealed that androgen deprivation therapy was associated with changes in self-reported cognitive function on either FACT-Cog scale. Mood and fatigue correlated with changes in self-reported cognitive function. The relationship between self-reported and objective cognitive measures was weak (maximum Spearman correlation coefficient 0.14) and only 2 of 30 correlations were statistically significant. CONCLUSIONS: A total of 12 months of androgen deprivation therapy were not associated with self-reported cognitive function changes in older men with nonmetastatic prostate cancer.

Responses of two marine top predators to an offshore wind farm.

Quantifying the likely effects of offshore wind farms on wildlife is fundamental before permission for development can be granted by any Determining Authority. The effects on marine top predators from displacement from important habitat are key concerns during offshore wind farm construction and operation. In this respect, we present evidence for no significant displacement from a UK offshore wind farm for two broadly distributed species of conservation concern: common guillemot (Uria aalge) and harbor porpoise (Phocoena phocoena). Data were collected during boat-based line transect surveys across a 360 km2 study area that included the Robin Rigg offshore wind farm. Surveys were conducted over 10 years across the preconstruction, construction, and operational phases of the development. Changes in guillemot and harbor porpoise abundance and distribution in response to offshore wind farm construction and operation were estimated using generalized mixed models to test for evidence of displacement. Both common guillemot and harbor porpoise were present across the Robin Rigg study area throughout all three development phases. There was a significant reduction in relative harbor porpoise abundance both within and surrounding the Robin Rigg offshore wind farm during construction, but no significant difference was detected between the preconstruction and operational phases. Relative common guillemot abundance remained similar within the Robin Rigg offshore wind farm across all development phases. Offshore wind farms have the potential to negatively affect wildlife, but further evidence regarding the magnitude of effect is needed. The empirical data presented here for two marine top predators provide a valuable addition to the evidence base, allowing future decision making to be improved by reducing the uncertainty of displacement effects and increasing the accuracy of impact assessments.

pH-Responsive Schizophrenic Diblock Copolymers Prepared by Polymerization-Induced Self-Assembly.

Polymerization-induced self-assembly (PISA) is used for the highly convenient and efficient preparation of ampholytic diblock copolymer nanoparticles directly in acidic aqueous solution. Cationic nanoparticles comprising a protonated polyamine stabilizer block and a hydrophobic polyacid core-forming block are formed at pH 2. Micelle inversion occurs at pH 10 to produce anionic nanoparticles with an ionized polyacid stabilizer block and a hydrophobic polyamine core-forming block. Macroscopic precipitation occurs at around pH 6-7, which lies close to the isoelectric point of this ampholytic diblock copolymer. Incorporation of fluorescein and rhodamine dye labels into the acid and amine blocks, respectively, leads to dual-color bifluorescent self-reporting pH-responsive nanoparticles.

Effects of long-term androgen deprivation therapy on cognitive function over 36 months in men with prostate cancer.

BACKGROUND: Many men with prostate cancer (PC) require long-term androgen deprivation therapy (ADT), but to the authors' knowledge, its effects on cognitive function beyond 1 year are not described. METHODS: Three groups of men aged ≥50 years who were matched based on age and education were enrolled: 77 patients with nonmetastatic PC who initiated continuous ADT, 82 patients with PC who were not receiving ADT (PC controls), and 82 healthy controls. A battery of 14 neuropsychological tests, examining 8 cognitive domains, was administered on 5 occasions over 36 months. Changes in cognitive scores over time were analyzed using 3 approaches: linear mixed effects regression, the percentage of participants per group with declines in ≥1/2 cognitive tests, and a global summary of cognitive change. RESULTS: The mean age of the study subjects was 68.9 years, with a median of 16 years of education. In mixed effects models adjusted for age and education, ADT use was not found to be associated with significant changes over time in any cognitive test compared with healthy controls. The percentage of participants declining by ≥1.5 standard deviations in ≥2 tests or ≥2 standard deviations in ≥1 tests was similar across groups. A global summary of cognitive change found no statistically significant worsening of cognitive function among ADT users compared with controls. Sensitivity analyses adjusting for duration of ADT and using multiple imputation for missing data did not materially alter the study findings. CONCLUSIONS: The ongoing use of ADT for up to 36 months does not appear to be associated with cognitive decline. Cancer 2017;123:237-244. © 2016 American Cancer Society.

The Relationship Between Serotonin-2A Receptor and Cognitive Functions in Nondemented Parkinson's Disease Patients with Visual Hallucinations.

BACKGROUND: There is growing evidence that the serotonergic system, in particular serotonin 2A receptors, is involved in neuropsychiatric symptoms in Parkinson's disease (PD), including cognitive processing and visual hallucinations. However, the relationship between serotonin 2A receptor availability, visual hallucinations, and cognitive profile is unknown. The objective of this study was to investigate the level of serotonin 2A receptor availability in brain regions affected by visual hallucinations and to test the association with cognitive/behavioral changes in patients who have PD with visual hallucinations. METHODS: Nondemented patients who had PD with (n = 11) and without (n = 8) visual hallucinations and age-matched controls (n = 10) were recruited. All participants completed neuropsychological testing, which consisted of visuoperceptual, executive, memory, language, and frontal-behavioral function. Positron emission tomography scans using [18F]setoperone, a serotonin 2A antagonist radioligand, were acquired in patients with PD, and a parametric binding potential map of [18F]setoperone was calculated with the simplified reference tissue model using the cerebellum as a reference. RESULTS: Patients who had PD with visual hallucinations exhibited significantly lower scores on measures of executive and visuoperceptual functions compared with age-matched controls. These changes were paralleled by decreased [18F]setoperone binding in the right insula, bilateral dorsolateral prefrontal cortex, right orbitofrontal cortex, right middle temporal gyrus, and right fusiform gyrus. The psychometric correlation analysis revealed significant relationships among tests associated with visuoperceptual function, memory and learning, and serotonin 2A binding in different prefrontal and ventral visual stream regions. There was also reduced serotonin 2A receptor binding in patients who had PD with depression. CONCLUSIONS: These findings support a complex interaction between serotonin 2A receptor function and cognitive processing in patients who have PD with visual hallucinations.

Medical Management of Parkinson's Disease after Initiation of Deep Brain Stimulation.

In this review, we have gathered all the available evidence to guide medication management after deep brain stimulation (DBS) in Parkinson's disease (PD). Surprisingly, we found that almost no study addressed drug-based management in the postoperative period. Dopaminergic medications are usually reduced, but whether the levodopa or dopamine agonist is to be reduced is left to the personal preference of the treating physician. We have summarized the pros and cons of both approaches. No study on the management of cognitive problems after DBS has been done, and only a few studies have explored the pharmacological management of such DBS-resistant symptoms as voice (amantadine), balance (donepezil) or gait disorders (amantadine, methylphenidate). As for the psychiatric problems so frequently reported in PD patients, researchers have directed their attention to the complex interplay between stimulation and reduction of dopaminergic drugs only recently. In conclusion, studies addressing medical management following DBS are still needed and will certainly contribute to the ultimate success of DBS procedures.

Oxidative damage of copper chloride overload to the cultured rat astrocytes.

Disorders of copper metabolism are associated with neurological dysfunction including Wilson's disease (WD). WD is a autosomal recessive disorder caused by mutations in the ATP7B gene resulting in the inability of the hepatocytes to remove excess copper. Gradual copper accumulation causes damage to liver, brain and other organs manifesting in liver disease, neurological and psychiatric symptoms. Also scond copper-neurometaboic disorder: Menkes disease charaterized with mutated ATP7A gene, is ralated with abnormally neuroal transmission and synaptogenesis. Parkinson's disease and Alzheimer's disease both are refered to some degree of copper/iron metabolism changes. The precise mechanisms by which excess copper causes neurological damage remain to be elucidated. In this study, we aimed to investigate the influence of excessive amounts of Cu(2+) on the oxidative damage response and survival of primary astrocytes from newborn rats. Primary cultured rat astrocytes were divided into three groups: 30 µmol/L CuCl2, 100 µmol/L CuCl2 and control. At 12, 24, 48, 96 and 120 hours of CuCl2 intervention, cell viability, intracellular reduced glutathione level and glutathion reductase activity, and nitric oxide secretion were determined. It was found that 30 µmol/L CuCl2 might stimulate the exaltation and the compensatory proliferation of astrocytes. The survival rate of astrocytes in the 100 µmol/L CuCl2 group was significantly decreased relative to the 30 µmol/L CuCl2 group. At 24 hours of CuCl2 intervention, intracellular reduced glutathione level and glutathion reductase activity were significantly decreased in the 100 µmol/L CuCl2 group compared to the control group. At 120 hours of CuCl2 intervention, nitric oxide secretion in the 100 µmol/L CuCl2 group was significantly greater than in the control group. Under pathological conditions, excessive amounts of Cu(2+) greatly damaged the growth and proliferation of astrocytes, reduced the anti-oxidative capacity of astrocytes by reducing intracellular glutathione level and glutathion reductase activity, worsened oxidative stress, and activated inflammation pathway by increasing nitric oxide secretion. By the way, all these findings might provide potential molecular therapeutic targets for the neurodegenerative diseases related Cu(2+) Metabolic Disorders, e.g., Wilson's disease, Parkinson's disease and Alzheimer's disease.

A Critical Appraisal of RAFT-Mediated Polymerization-Induced Self-Assembly.

Recently, polymerization-induced self-assembly (PISA) has become widely recognized as a robust and efficient route to produce block copolymer nanoparticles of controlled size, morphology, and surface chemistry. Several reviews of this field have been published since 2012, but a substantial number of new papers have been published in the last three years. In this Perspective, we provide a critical appraisal of the various advantages offered by this approach, while also pointing out some of its current drawbacks. Promising future research directions as well as remaining technical challenges and unresolved problems are briefly highlighted.

Progression of neuropsychiatric and cognitive features due to exons 2 to 5 deletion in the epsilon-sarcoglycan gene: a case report.

Physical symptoms of myoclonus dystonia due to epsilon-sarcoglycan mutations are well documented; however, the progression of neuropsychiatric and cognitive symptoms remains unclear. We present a case of a 34-year-old woman with early childhood onset of myoclonic jerks, dystonic posture and developmental delay due to exons 2 to 5 deletion in the epsilon-sarcoglycan gene. Over time, she developed neuropsychiatric symptoms. She underwent bilateral deep brain stimulation of the ventral intermediate nucleus of the thalamus for her motor symptoms, which greatly improved but she exhibited slow deterioration of her neuropsychiatric and cognitive symptoms, particularly apathy, aggression and severe executive dysfunction.

Salivary cortisol and explicit memory in postmenopausal women using hormone replacement therapy.

Circulating cortisol levels are known to influence explicit memory in humans and other primates. The present study investigated salivary cortisol and its association with explicit memory performance in 99 postmenopausal women (64 treated with conjugated equine estrogens or estradiol, and 35 matched controls not using any form of hormone therapy). Controls were compared with treated women taking estrogens alone (n=39), or taking estrogens in combination with a progestin (n=25). Mean time on hormone therapy was approximately 5 years, with initiation of treatment in close proximity to the onset of menopause. Explicit memory was assessed with the California Verbal Learning Test (CVLT). Saliva was collected before (basal or resting sample) and after (post-test sample) completing a set of cognitive tasks. Cortisol was measured using a high-sensitivity radioimmunoassay. Treated women were found to have higher resting cortisol concentrations than controls matched for time of day. Basal cortisol was a modest predictor of learning and memory on the CVLT. Higher cortisol was associated with better recall and fewer memory errors, which is consistent with experimental studies examining explicit memory under small increases in circulating cortisol load. Potential cumulative effects on the central nervous system of sustained exposure to mildly increased cortisol in conjunction with the long-term use of oral estrogens are discussed in the context of aging and dementia.