Search

Sheree A McCormick,1,2,* Kathryn R McDonald,1,2,* Sabina Vatter,1–3 Vasiliki Orgeta,4 Ellen Poliakoff,1,2 Sarah J Smith,5 Iracema Leroi1–3 1Division of Neuroscience and Experimental Psychology, University of Manchester, Manchester, UK; 2Manchester Academic Health Science Center (MAHSC), Manchester, UK; 3Greater Manchester Mental Health Foundation Trust, Manchester, UK; 4Division of Psychiatry, University College London, London, UK; 5Faculty of Health Studies, University of Bradford, Bradford, UK *These authors contributed equally to this work Background: Group-based psychosocial therapy, such as group Cognitive Stimulation Therapy, improves cognition and quality of life in people living with dementia. Neuropsychiatric symptoms and restricted mobility are common complications for people with Parkinson’s-related dementia (PRD) and may limit access to, and participation in, group activities. This study describes the development of a condition-specific, home-based psychosocial therapy for people with PRD ready to be trialled in a clinical population. Methods: By means of a multistage process, a draft therapy manual was developed in an iterative manner through collaboration with medical experts, researchers and Patient and Public Involvement (PPI) representatives. In stage 1, an extensive literature search of psychosocial therapies for dementia with potential relevance for Parkinson’s disease (PD) was undertaken to select a candidate therapy for adaptation. In stage 2, qualitative feedback from stakeholders and intelligence regarding existing nonpharmacological therapies for cognitive impairment in PD was combined to produce a prototype therapy manual. In stage 3, the manual was field tested in: 1) a home-setting using a 25-item assessment tool; and 2) at a local PD support group with PPI representatives. Based on the feedback from this phase, final design modifications were implemented and a draft therapy manual produced. Results: The manual was developed in an iterative manner. Interview and focus group transcripts identified three enduring themes: manual form and content, therapy acceptability by people with PRD, and companion guidance and support. Major adaptations included: removal of discrete levels of task complexity, removal of images that were potentially hallucinogenic or lacked clarity, and updating of the content. Conclusion: We have successfully developed a Cognitive Stimulation Therapy-based psychosocial therapy specifically adapted for people with PRD. The therapy is ready to trial in a pilot randomized controlled study. Keywords: Parkinson’s disease, cognitive stimulation, MRC framework, intervention development

Abstract Background Non-invasive micro-ultrasound was evaluated as a method to quantify intrauterine growth phenotypes in mice. Improved methods are required to accelerate research using genetically-altered mice to investigate the interactive roles of genes and environments on embryonic and placental growth. We determined (1) feasible age ranges for measuring specific variables, (2) normative growth curves, (3) accuracy of ultrasound measurements in comparison with light microscopy, and (4) weight prediction equations using regression analysis for CD-1 mice and evaluated their accuracy when applied to other mouse strains. Methods We used 30–40 MHz ultrasound to quantify embryonic and placental morphometry in isoflurane-anesthetized pregnant CD-1 mice from embryonic day 7.5 (E7.5) to E18.5 (full-term), and for C57Bl/6J, B6CBAF1, and hIGFBP1 pregnant transgenic mice at E17.5. Results Gestational sac dimension provided the earliest measure of conceptus size. Sac dimension derived using regression analysis increased from 0.84 mm at E7.5 to 6.44 mm at E11.5 when it was discontinued. The earliest measurement of embryo size was crown-rump length (CRL) which increased from 1.88 mm at E8.5 to 16.22 mm at E16.5 after which it exceeded the field of view. From E10.5 to E18.5 (full term), progressive increases were observed in embryonic biparietal diameter (BPD) (0.79 mm to 7.55 mm at E18.5), abdominal circumference (AC) (4.91 mm to 26.56 mm), and eye lens diameter (0.20 mm to 0.93 mm). Ossified femur length was measureable from E15.5 (1.06 mm) and increased linearly to 2.23 mm at E18.5. In contrast, placental diameter (PD) and placental thickness (PT) increased from E10.5 to E14.5 then remained constant to term in accord with placental weight. Ultrasound and light microscopy measurements agreed with no significant bias and a discrepancy of less than 25%. Regression equations predicting gestational age from individual variables, and embryonic weight (BW) from CRL, BPD, and AC were obtained. The prediction equation BW = -0.757 + 0.0453 (CRL) + 0.0334 (AC) derived from CD-1 data predicted embryonic weights at E17.5 in three other strains of mice with a mean discrepancy of less than 16%. Conclusion Micro-ultrasound provides a feasible tool for in vivo morphometric quantification of embryonic and placental growth parameters in mice and for estimation of embryonic gestational age and/or body weight in utero.

Abstract Background The lung is divided into two major compartments: the alveolar space and the parenchyma. The alveolar macrophages are the first line of leukocytes in the lung taking up incoming microbes or microbial antigens whereas the parenchymal dendritic cells (DCs) are believed to be the sole potent antigen presenting cells (APCs) in the lung. Both resting alveolar macrophages and parenchymal DCs express CD11c. Several important questions remain to be elucidated: 1] to which extent the alveolar space and lung parenchymal CD11c+ APCs differ in their phenotype and ability to activate naïve T cells; 2] whether they differ in their ability to activate antigen-experienced or -primed T cells; and 3] whether these lung CD11c+ APC populations differ from the splenic CD11c+ APCs which have been commonly used for understanding APC biology. Results CD11c+ APCs from the alveolar space, lung parenchyma, and the spleen display differential co-stimulatory molecule expression and cytokine responsiveness upon stimulation. Alveolar space APCs are weak activators of naïve T cells compared to lung parenchymal and splenic CD11c+ APC populations. However, alveolar space APCs are able to potently activate the in vivo microbial antigen-primed T cells to a similar extent as lung parenchymal and splenic APCs. Conclusion Together our findings indicate that alveolar CD11c+ APCs have a specialized T cell-activating function, capable of activating antigen-primed, but not naïve, T cells whereas lung CD11c+ APCs are capable of activating both the naïve and antigen-primed T cell populations.

EEG studies play a crucial role in enhancing our understanding of brain development across the lifespan. The increasing clinical and policy implications of EEG research underscore the importance of utilizing reliable EEG measures and increasing the reproducibility of EEG studies. However, important data characteristics like reliability, effect sizes, and data quality metrics are often underreported in pediatric EEG studies. This gap in reporting could stem from the lack of accessible computational tools for quantifying these metrics for EEG data. To help address the lack of reporting, we developed a toolbox that facilitates the estimation of internal consistency reliability, effect size, and standardized measurement error with user-friendly software that facilitates both computing and interpreting these measures. In addition, our tool provides subsampled reliability and effect size in increasing numbers of trials. These estimates offer insights into the number of trials needed for detecting significant effects and reliable measures, informing the minimum number of trial thresholds for the inclusion of participants in individual difference analyses and the optimal trial number for future study designs. Importantly, our toolbox is integrated into commonly used preprocessing pipelines to increase the estimation and reporting of data quality metrics in developmental neuroscience., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Caregivers play an outsized role in shaping early life experiences and development, but we often lack mechanistic insight into how exactly caregiver behavior scaffolds the neurodevelopment of specific learning processes. Here, we capitalized on the fact that caregivers differ in how predictable their behavior is to ask if infants' early environmental input shapes their brains' later ability to learn about predictable information. As part of an ongoing longitudinal study in South Africa, we recorded naturalistic, dyadic interactions between 103 (46 females and 57 males) infants and their primary caregivers at 3-6 months of age, from which we calculated the predictability of caregivers' behavior, following caregiver vocalization and overall. When the same infants were 6-12-months-old they participated in an auditory statistical learning task during EEG. We found evidence of learning-related change in infants' neural responses to predictable information during the statistical learning task. The magnitude of statistical learning-related change in infants' EEG responses was associated with the predictability of their caregiver's vocalizations several months earlier, such that infants with more predictable caregiver vocalization patterns showed more evidence of statistical learning later in the first year of life. These results suggest that early experiences with caregiver predictability influence learning, providing support for the hypothesis that the neurodevelopment of core learning and memory systems is closely tied to infants' experiences during key developmental windows., (© 2024 The Author(s). Developmental Science published by John Wiley & Sons Ltd.)

Electroencephalography (EEG) is an important tool in the field of developmental cognitive neuroscience for indexing neural activity. However, racial biases persist in EEG research that limit the utility of this tool. One bias comes from the structure of EEG nets/caps that do not facilitate equitable data collection across hair textures and types. Recent efforts have improved EEG net/cap design, but these solutions can be time-intensive, reduce sensor density, and are more difficult to implement in younger populations. The present study focused on testing EEG sensor net designs over infancy. Specifically, we compared EEG data quality and retention between two high-density saline-based EEG sensor net designs from the same company (Magstim EGI, Whitland, UK) within the same infants during a baseline EEG paradigm. We found that within infants, the tall sensor nets resulted in lower impedances during collection, including lower impedances in the key online reference electrode for those with greater hair heights and resulted in a greater number of usable EEG channels and data segments retained during pre-processing. These results suggest that along with other best practices, the modified tall sensor net design is useful for improving data quality and retention in infant participants with curly or tightly-coiled hair., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Motor (re)learning via technology-dependent therapy has the potential to complement traditional therapies available to older adults living with stroke after hospital discharge and increase therapy dose. To date, little is known about the feasibility of technology-dependent therapy in a home setting for this population., Objective: To develop a technology-dependent therapy that provides mental and physical training for older adults with stroke and assess feasibility. Specifically we ask, "Can it work"?, Design: Single group repeated measures., Methods: 13 participants, aged 18 years and over, were recruited over a six-month period. All participants had mild upper limb impairment following a stoke and were no longer receiving intensive rehabilitation. All participants received 18 days of technology-dependent therapy in their own home. Information was gathered on recruitment and retention, usability, and suitability of outcome measures., Results: 11 participants completed the study. The recruitment rate (number recruited/number canvassed; 10.7%) suggests 1907 participants would need to be canvassed to recruit the necessary sample size ( n = 204) for a definitive trial designed to provide 90% power at 5% level of significance to detect a clinically meaningful difference of 5.7 points on the Action Research Arm Test. The usability of the application was rated as exceptional on the System Usability Scale. Effectiveness cannot be determined from this study; however, there was a trend for improvement in measures of upper limb function and emotional well-being. Limitations . The study was limited by a relatively small sample size and lack of control group., Conclusions: This study demonstrated proof of concept of a technology-dependent therapy for upper limb rehabilitation following stroke. The data suggest a definitive trial is feasible, additional strategies to improve recruitment should be considered. Outcome measures aligned with the residual motor function of participants are required., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2022 Sheree A. McCormick et al.)

Social interactions between parents and children are important for developing theory of mind, but these may be disrupted by aspects of the proximal home environment. The current study observed maternal sensitivity and its associations with child theory of mind and the housing environment (index by clutter and crowding) in a sample of mothers and their 3.5-year-old twins (N = 250 children). Maternal sensitivity and housing environment were measured from experimenter report and child theory of mind was measured through behavioural tasks. Results show that the association between maternal sensitivity and child theory of mind was moderated by the housing environment, where the positive associations between maternal sensitivity and child theory of mind were only observed at lower levels of clutter and crowding in the housing environment. Additional contextual variables and processes are discussed., (© 2022 The British Psychological Society.)

Background: Postnatal maternal anxiety is common (estimates as high as 40% prevalence) and is associated with altered mother-infant interactions (e.g., reduced maternal emotional expression and engagement). Neural circuitry supporting infants' face and emotion processing develops in their first year. Thus, early exposure to maternal anxiety may impact infants' developing understanding of emotional displays. We examine whether maternal anxiety is associated with individual differences in typically developing infants' neural responses to emotional faces., Methods: One hundred and forty two mother-infant dyads were assessed when infants were 5, 7, or 12 months old. Infants' electroencephalographic (EEG) data were recorded while passively viewing female happy, fearful, and angry faces. Three event-related potential (ERP) components, each linked to face and emotion processing, were evaluated: NC, N290, and P400. Infant ERP amplitude was related to concurrent maternal-report anxiety assessed with the Spielberger State-Trait Anxiety Inventory (Trait form)., Results: Greater maternal anxiety predicted more negative NC amplitude for happy and fearful faces in left and mid-central scalp regions, beyond covarying influences of maternal depression symptoms, infant negative emotionality, and infant age., Conclusions: Postnatal maternal anxiety is related to infants' neural processing of emotional expressions. Infants of mothers endorsing high trait anxiety may need additional attentional resources to process happy and fearful faces (expressions less likely experienced in mother-infant interactions). Future research should investigate mechanisms underlying this association, given possibilities include experiential, genetic, and prenatal factors., (© 2021 Association for Child and Adolescent Mental Health.)

Parents' responses to children's negative emotional states play a key role in the socialization of emotion regulation skills in childhood. Much of the prior research on child ER has focused on early development using cross-sectional designs. The current study addresses these gaps by using a longitudinal design to examine individual differences of ER at two times points in middle childhood. We examined the development of children's ER by testing hypotheses about the interplay of parent response to emotions and household chaos in the prediction of individual differences in children's ER. Participants were the mothers of children at 6 and 9 years of age among 224 families in a socioeconomically diverse sample that was part of an ongoing longitudinal study. Mothers completed questionnaires regarding themselves, their children, and their home environment. Mothers' reports of better child ER at both time points were positively associated with mothers' more supportive responses and negatively associated with mothers' less non-supportive responses, as well as lower household chaos. Chaos statistically moderated the link between non-supportive parental responses to emotion and child ER, but only at 6 years of age. The strength of the link between child ER and non-supportive parental responses to emotions was strong only at lower levels of household chaos. At the beginning of middle childhood, family processes linking parent responses to child emotions and children's developing ER may not function at higher levels of household chaos., Competing Interests: The authors have no conflicts of interest.

This report describes the evaluation of the psychometric and clinimetric properties of nine self-report measures completed by informal care partners of individuals with mild cognitive impairment or dementia in Parkinson's disease and dementia with Lewy bodies. One hundred thirty-six care partners completed measures on relationship satisfaction, burden, stress, mood, resilience, health, quality of life, and feelings related to care provision. Psychometric properties, such as internal consistency, convergent validity, floor and ceiling effects, completion rate and data missingness, as well as clinimetric properties, such as time to administer, ease of scoring, readability and availability of the scales, were examined. Additionally, the design of the measure development studies was assessed with the 2018 COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) Risk of Bias checklist. Participants were mostly married women (>85%) with a mean age of 69.4 years. The methodological quality of the design of all measure development studies was "inadequate." Five widely applied measures (Zarit Burden Interview, Hospital Anxiety and Depression Scale, Short Form 12 Health Survey, Relatives' Stress Scale, and EuroQoL-5D) and two less researched instruments (Brief Resilience Scale and Relationship Satisfaction Scale) had high internal consistency and completion rates, moderate to strong convergent validity, low missingness and floor effects, and excellent clinical utility ratings. Two scales (Dyadic Relationship Scale and Family Caregiving Role) received poor psychometric ratings, and their usage among informal care partners is not recommended. In conclusion, well-validated and widely used measures received strong psychometric and clinimetric ratings. Future studies are required to determine the most reliable, valid and robust caregiver-reported measures.

When children transition to school between the ages of 4 and 6 years, they must learn to control their attention and behavior to be successful. Concurrently, executive function (EF) is an important skill undergoing significant development in childhood. To understand changes occurring during this period, we examined the role of parenting in the development of children's EF from 4 to 6 years old. Participants were mother and child dyads (N = 151). Children completed cognitive tasks to assess overall EF at age 4 and age 6. At both time points, mothers and children completed interaction tasks which were videotaped and coded to assess various parenting dimensions. Results indicated that children with high EF at age 4 were more likely to have high EF at age 6. In addition, results suggested that higher levels of positive parenting across the transition to school promote stability of individual differences in EF., Competing Interests: Conflict of Interest Statement: The authors have no conflicts of interest to disclose.

Objectives: To explore and compare levels of mental health, care burden, and relationship satisfaction among caregiving spouses of people with mild cognitive impairment or dementia in Parkinson disease (PD-MCI or PDD) or dementia with Lewy bodies (DLB)., Methods: Spouses (n = 136) completed measures of mood, stress, resilience, general health, quality of life, care burden, and relationship satisfaction, as well as sociodemographic factors. Additionally, data on motor and neuropsychiatric symptom severity of people with PD-MCI, PDD, or DLB were obtained in a subsample., Results: Most spouses were married women (>85%) who provided a median of 4 years of care and 84 hours of weekly care. Among these, relationship dissatisfaction, stress, anxiety, care burden, and feelings of resentment were common. Spouses of people with PDD and DLB had significantly higher rates of burden, resentment, and depression compared to spouses of people with PD-MCI. Furthermore, unique group differences emerged whereby spouses of people with PDD had significantly longer duration of care provision, higher stress, more relationship dissatisfaction, and fewer positive interactions, compared to PD-MCI group, whereas anxiety and lower levels of mental health were prominent in spouses of people with DLB, compared to PD-MCI group. Despite this, the majority of spouses reported good quality of life, resilience, and satisfaction with the caring role., Conclusion: Both PDD and DLB significantly contribute to poorer mental health and higher levels of care burden in spouses. Clinicians should actively screen the risk of burden, stress, depression, and anxiety among caregiving spouses of people with these conditions.

Processing of positive and negative facial expressions in infancy follows a distinct course with a bias towards fearful facial expressions starting at 7 months of age; however, little is known about the developmental trajectory of fear processing and other facial expressions, and if this bias is driven by specific regions of the face. This study used eye tracking to examine the processing of positive and negative emotional faces in independent groups of 5- (n = 43), 7- (n = 60), and 12-month-old infants (n = 70). Methods: Infants were shown static images of female faces exhibiting happy, anger, and fear expressions, for one-second each. Total looking time and looking time for areas of interest (AOIs) including forehead and eyes (top), mouth and chin (bottom), and contour of each image were computed. Infants across all ages looked longer to fear faces than angry or happy faces. Negative emotions generally elicited greater looking times for the top of the face than did happy faces. In addition, we also found that at 12 months of age infants looked longer for the bottom of the faces than did 5-month-olds. Our study suggests that the visual bias to attend longer to fearful faces may be in place by 5 months of age, and between 5 and 12 months of age, there seems to be a developmental shift towards looking more to the bottom of the faces. STATEMENT OF CONTRIBUTION: What is already known in this subject? Bias for fear face processing is present at 7 months of age. Using older data collection systems, we have some idea about which facial features recruit infant attention. What the present study adds? Well-controlled paradigm that examines both positive and negative facial expressions, to different areas of interest in the face. Use of the same paradigm to test a cross-sectional sample of infants in distinct developmental stages - 5, 7, and 12 months., (© 2019 The British Psychological Society.)

Cognitive stimulation therapy (CST) is widely used with people with dementia, but there is no evidence of its efficacy in mild cognitive impairment or dementia in Parkinson's disease (PD-MCI; PDD) or dementia with Lewy bodies (DLB). We aimed to explore the impact of 'CST-PD', which is home-based, individualized CST adapted for this population. In a single-blind, randomized controlled exploratory pilot trial (RCT), we randomized 76 participant-dyads [PD-MCI ( n = 15), PDD ( n = 40), DLB ( n = 21) and their care partners] to CST-PD or treatment as usual (TAU). CST-PD involves home-based cognitively stimulating and engaging activities delivered by a trained care partner. Exploratory outcomes at 12 weeks included cognition (Addenbrooke's Cognitive Evaluation; ACE-III), neuropsychiatric symptoms and function. In care partners, we assessed burden, stress and general health status. Relationship quality and quality of life were assessed in both dyad members. At 12 weeks, the ACE-III showed a nonstatistically significant improvement in the CST-PD group compared with the TAU group, although neuropsychiatric symptoms increased significantly in the former. In contrast, care partners' quality of life ( d = 0.16) and relationship quality ('satisfaction', d = 0.01; 'positive interaction', d = 0.55) improved significantly in the CST-PD group, and care burden ( d = 0.16) and stress ( d = 0.05) were significantly lower. Qualitative findings in the CST-PD recipients revealed positive 'in the moment' responses to the intervention, supporting the quantitative results. In conclusion, care-partner-delivered CST-PD may improve a range of care-partner outcomes that are important in supporting home-based care. A full-scale follow-up RCT to evaluate clinical and cost effectiveness is warranted., Competing Interests: Conflict of interest statement: VO has a patent: iCST Manual. No other authors have received any funding from any institution, including personal relationships, interests, grants, employment, affiliations, patents, inventions, honoraria, consultancies, royalties, stock options/ownership or expert testimony for the last 12 months. VO has a patent: iCST Manual. The other authors declare that there is no conflict of interest.

Background: Drug-based therapeutic approaches for Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are moderately effective and not always tolerated. Tailoring psychosocial approaches in PDD and DLB may offer additional support and improve outcomes. We adapted home-based, care partner-delivered Cognitive Stimulation Therapy (CST) for individuals with PDD or DLB and their care partners (CST-PD)., Objectives: To evaluate the feasibility, acceptability, and tolerability of CST-PD., Methods: This randomised controlled trial used mixed methods, including a process evaluation. People with PDD, DLB or mild cognitive impairment in PD (PD-MCI) and their care partners were randomised to 12 weeks of treatment as usual (TAU) or CST-PD. Outcomes were feasibility of the study conduct (i.e., recruitment, retention rate) and acceptability and tolerability of the intervention. Measures included rating scales, researcher field notes, therapy diaries, and exploratory clinical and care partner efficacy measures., Results: The recruitment target was met with 76 consenting participant-dyads. Retention in both arms was high at over 70%. More than 90% of dyads undertook discrete sessions greater than 20 min duration, but the average number of sessions completed was lower than the recommended dose. Acceptability ratings (i.e., interest, motivation and sense of achievement) of the intervention were high. Participants reported no serious adverse events related to the intervention., Conclusions: The field of psychosocial interventions for PDD and DLB is newly emerging, and we demonstrated that this type of intervention is acceptable and well tolerated. Evaluating its clinical effectiveness in a full-scale randomized controlled clinical trial is warranted., Trial Registration Number: The trial is a psychosocial intervention with an allocated ISRCTN number 11455062.

In the present study we examined the neural correlates of facial emotion processing in the first year of life using ERP measures and cortical source analysis. EEG data were collected cross-sectionally from 5- (N = 49), 7- (N = 50), and 12-month-old (N = 51) infants while they were viewing images of angry, fearful, and happy faces. The N290 component was found to be larger in amplitude in response to fearful and happy than angry faces in all posterior clusters and showed largest response to fear than the other two emotions only over the right occipital area. The P400 and Nc components were found to be larger in amplitude in response to angry than happy and fearful faces over central and frontal scalp. Cortical source analysis of the N290 component revealed greater cortical activation in the right fusiform face area in response to fearful faces. This effect started to emerge at 5 months and became well established at 7 months, but it disappeared at 12 months. The P400 and Nc components were primarily localized to the PCC/Precuneus where heightened responses to angry faces were observed. The current results suggest the detection of a fearful face in infants' brain can happen shortly (~200-290 ms) after the stimulus onset, and this process may rely on the face network and develop substantially between 5 to 7 months of age. The current findings also suggest the differential processing of angry faces occurred later in the P400/Nc time window, which recruits the PCC/Precuneus and is associated with the allocation of infants' attention., (© 2018 John Wiley & Sons Ltd.)

Background: the complex and progressive nature of Parkinson's disease (PD) and cognitive impairment may necessitate a care provider, a role which is frequently undertaken by a spouse. Providing and receiving care related to dementia impacts on a couple's partnership and may result in decreased intimacy and relationship satisfaction., Objective: to explore the changes in long-term intimate relationships in Parkinson's-related dementia, as perceived by spouses providing care to their partners., Methods: participants were identified using purposive sampling. Twelve female spouses whose partners had PD and mild cognitive impairment (PD-MCI), PD dementia (PDD) or dementia with Lewy bodies (DLB) completed semi-structured face-to-face interviews. Transcribed data were analysed using inductive thematic analysis. The consolidated criteria for reporting qualitative research (COREQ) were applied., Results: couples' relationship satisfaction, intimacy and communication had already reduced in the mild cognitive impairment stage of PD, but the decline in these domains was markedly greater with the emergence of dementia. Increased spousal care responsibilities resulted in partners spending more time together, but feeling emotionally more distanced. Several participants' roles transitioned from spouse to caregiver and they reported feelings of frustration, resentment, anger, sadness and a worry for the future. Cognitive impairment was significantly harder to accept, manage and cope with than the motor symptoms of PD. Spouses acknowledged their marital commitments and exhibited acceptance, adjustment, resilience and various coping strategies., Conclusion: this is the first study exploring relationship satisfaction in Parkinson's-related dementia and has provided valuable insight into the changing patterns of intimate relationships., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Geriatrics Society.)

Introduction: Parkinson's disease (PD) with mild cognitive impairment (MCI-PD) or dementia (PDD) and dementia with Lewy bodies (DLB) are characterised by motor and 'non-motor' symptoms which impact on quality of life. Treatment options are generally limited to pharmacological approaches. We developed a psychosocial intervention to improve cognition, quality of life and companion burden for people with MCI-PD, PDD or DLB. Here, we describe the protocol for a single-blind randomised controlled trial to assess feasibility, acceptability and tolerability of the intervention and to evaluate treatment implementation. The interaction among the intervention and selected outcome measures and the efficacy of this intervention in improving cognition for people with MCI-PD, PDD or DLB will also be explored., Methods and Analysis: Dyads will be randomised into two treatment arms to receive either 'treatment as usual' (TAU) or cognitive stimulation therapy specifically adapted for Parkinson's-related dementias (CST-PD), involving 30 min sessions delivered at home by the study companion three times per week over 10 weeks. A mixed-methods approach will be used to collect data on the operational aspects of the trial and treatment implementation. This will involve diary keeping, telephone follow-ups, dyad checklists and researcher ratings. Analysis will include descriptive statistics summarising recruitment, acceptability and tolerance of the intervention, and treatment implementation. To pilot an outcome measure of efficacy, we will undertake an inferential analysis to test our hypothesis that compared with TAU, CST-PD improves cognition. Qualitative approaches using thematic analysis will also be applied. Our findings will inform a larger definitive trial., Ethics and Dissemination: Ethical opinion was granted (REC reference: 15/YH/0531). Findings will be published in peer-reviewed journals and at conferences. We will prepare reports for dissemination by organisations involved with PD and dementia., Trial Registration Number: ISRCTN (ISRCTN11455062)., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: To report on the presentation, radiography, histology, and treatment of 8 cases of extranodal Rosai-Dorfman disease involving the orbit., Methods: Multicenter retrospective case series., Results: Five males and 3 females had a median age of 10 years (range 2-78 years). Presenting signs and symptoms included proptosis, periorbital pain, palpable mass, blepharoptosis, decreased vision, diplopia, impaired extraocular motility, and afferent pupillary defect. Four patients had bilateral orbital disease, while 4 had unilateral disease. Six cases were extraconal, 1 was intraconal, and 1 was both intra- and extra-conal. Four cases had only extranodal disease without lymphadenopathy (3 of which had localized orbital disease). Diagnosis was confirmed by exam, orbital, and/or systemic radiography, and biopsy in all cases. Treatment strategies included excision or debulking, systemic corticosteroids, chemotherapy, radiotherapy, observation or a combination thereof. At last follow up, 4 patients were disease free, while 4 had residual improved disease., Conclusions: Rosai-Dorfman disease of the orbit is a rare clinical entity. Purely extranodal disease is rare, with isolated orbital disease being exceedingly rare. This study is unique in that 4 of 8 patients had strictly isolated extranodal disease of the orbit. A large majority of the cases had disease in the extraconal space, contrasting with previous reports. In addition, lacrimal gland disease, particularly bilateral involvement, was prominent in the current study. Although there is no consensus on treatment, surgical excision should be attempted if plausible in symptomatic patients especially if the orbit represents a localized site of disease.

Changes in atmosphere and temperature are affecting multiple environmental indicators from extreme heat events to global air quality. Workers will be uniquely affected by climate change, and the occupational impacts of major shifts in atmospheric and weather conditions need greater attention. Climate change-related exposures most likely to differentially affect workers in the USA and globally include heat, ozone, polycyclic aromatic hydrocarbons, other chemicals, pathogenic microorganisms, vector-borne diseases, violence, and wildfires. Epidemiologic evidence documents a U-, J-, or V-shaped relationship between temperature and mortality. Whereas heat-related morbidity and mortality risks are most evident in agriculture, many other outdoor occupational sectors are also at risk, including construction, transportation, landscaping, firefighting, and other emergency response operations. The toxicity of chemicals change under hyperthermic conditions, particularly for pesticides and ozone. Combined with climate-related changes in chemical transport and distribution, these interactions represent unique health risks specifically to workers. Links between heat and interpersonal conflict including violence require attention because they pose threats to the safety of emergency medicine, peacekeeping and humanitarian relief, and public safety professionals. Recommendations for anticipating how US workers will be most susceptible to climate change include formal monitoring systems for agricultural workers; modeling scenarios focusing on occupational impacts of extreme climate events including floods, wildfires, and chemical spills; and national research agenda setting focusing on control and mitigation of occupational susceptibility to climate change.

Action observation interventions may have the potential to contribute to improved motor function in motor (re)learning settings by promoting functional activity and plasticity in the motor regions of the brain. Optimal methods for delivering such interventions, however, have yet to be established. This experiment investigated the effect on corticospinal excitability of manipulating the viewing instructions provided to participants (N = 21) prior to action observation. Specifically, motor evoked potential responses measured from the right hand muscles following single-pulse transcranial magnetic stimulation (TMS) to the left motor cortex were compared when participants were instructed to observe finger-thumb opposition movement sequences: (i) passively; (ii) with the intent to imitate the observed movement; or (iii) whilst simultaneously and actively imagining that they were performing the movement as they observed it. All three action observation viewing instructions facilitated corticospinal excitability to a greater extent than did observation of a static hand. In addition, the extent to which corticospinal excitability was facilitated was greater during combined observation and imagery, compared to passive observation. These findings have important implications for the design of action observation interventions in motor (re)learning settings, where instructions that encourage observers to simultaneously imagine themselves performing the observed movement may offer the current optimal method for improving motor function through action observation.

Previous studies in infants have shown that face-sensitive components of the ongoing electroencephalogram (the event-related potential, or ERP) are larger in amplitude to negative emotions (e.g., fear, anger) versus positive emotions (e.g., happy). However, it is still unclear whether the negative emotions linked with the face or the negative emotions alone contribute to these amplitude differences. We simultaneously recorded infant looking behaviors (via eye-tracking) and face-sensitive ERPs while 7-month-old infants viewed human faces or animals displaying happy, fear, or angry expressions. We observed that the amplitude of the N290 was greater (i.e., more negative) to angry animals compared to happy or fearful animals; no such differences were obtained for human faces. Eye-tracking data highlighted the importance of the eye region in processing emotional human faces. Infants that spent more time looking to the eye region of human faces showing fearful or angry expressions had greater N290 or P400 amplitudes, respectively., (© 2014 Wiley Periodicals, Inc.)

Purpose: Melanocytes are one of the major cellular components in the uvea. Interleukin-8/CXCL8 and monocyte chemoattractant protein-1 (MCP-1/CCL2) are the two most important proinflammatory chemokines. We studied the constitutive and lipopolysaccharide (LPS)-induced expression of IL-8 and MCP-1 in cultured human uveal melanocytes (UM) and explored the relevant signal pathways., Methods: Conditioned media and cells were collected from UM cultured in medium with and without stimulation of LPS. Interleukin-8 and MCP-1 proteins and mRNAs were measured using an ELISA kit and RT-PCR, respectively. Nuclear factor (NF)-κB in nuclear extracts and phosphorylated p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases1/2 (ERK1/2), and c-Jun N-terminal kinase1/2 (JNK1/2) in cells cultured with and without LPS were measured by ELISA kits. Inhibitors of p38 (SB203580), ERK1/2 (UO1026), JNK1/2 (SP600125), and NF-κB (BAY11-7082) were added to the cultures to evaluate their effects., Results: Low levels of IL-8 and MCP-1 proteins were detected in the conditioned media in UM cultured without serum. Lipopolysaccharide (0.01-1 μg/mL) increased IL-8 and MCP-1 mRNAs and proteins levels in a dose- and time-dependent manner, accompanied by a significant increase of phosphorylated JNK1/2 in cell lysates and NF-κB in nuclear extracts. Nuclear factor-κB and JNK1/2 inhibitors significantly blocked LPS-induced expression of IL-8 and MCP-1., Conclusions: This is the first report on the expression and secretion of chemokines by UM. The data suggest that UM may play a role in the pathogenesis of ocular inflammatory diseases., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Changes in heart rate are a useful physiological measure in infant studies. We present an algorithm for calculating the heart rate (HR) from oxyhemoglobin pulsation in functional near-infrared spectroscopy (fNIRS) signals. The algorithm is applied to data collected from 10 infants, and the HR derived from the fNIRS signals is compared against the HR as calculated by electrocardiography. We show high agreement between the two HR signals for all infants (r > 0.90), and also compare stimulus-related HR responses as measured by the two methods and find good agreement despite high levels of movement in the infants. This algorithm can be used to measure changes in HR in infants participating in fNIRS studies without the need for additional HR sensors.

Movement based interventions such as imagery and action observation are used increasingly to support physical rehabilitation of adults during early aging. The efficacy of these more covert approaches is based on an intuitively appealing assumption that movement execution, imagery and observation share neural substrate; alteration of one influences directly the function of the other two. Using eye movement metrics this paper reports findings that question the congruency of the three conditions. The data reveal that simulating movement through imagery and action observation may offer older adults movement practice conditions that are not constrained by the age-related decline observed in physical conditions. In addition, the findings provide support for action observation as a more effective technique for movement reproduction in comparison to imagery. This concern for imagery was also seen in the less congruent temporal relationship in movement time between imagery and movement execution suggesting imagery inaccuracy in early aging.

The aim of this paper is to provide a review of eye movements during action execution, action observation, and movement imagery. Furthermore, the paper highlights aspects of congruency in gaze metrics between these states. The implications of the imagery, observation, and action gaze congruency are discussed in terms of motor learning and rehabilitation. Future research directions are outlined in order to further the understanding of shared gaze metrics between overt and covert states. Suggestions are made for how researchers and practitioners can structure action observation and movement imagery interventions to maximize (re)learning.

Purpose: To determine the prevalence of herpes simplex virus type 1 (HSV-1) DNA in failed Descemet membrane stripping automated endothelial keratoplasty (DSAEK) grafts., Methods: A retrospective interventional case series of patients with DSAEK graft failure treated at the New York Eye and Ear Infirmary between January 2009 and July 2012 was performed. Repeat DSAEK, penetrating keratoplasty, or keratoprosthesis procedure was subsequently performed on eyes with failed grafts. All failed grafts were examined immunohistochemically and with qualitative real-time polymerase chain reaction for HSV-1 DNA. In HSV-1-positive cases, corneoscleral donor rims from the original DSAEK procedures were also examined immunohistochemically and with polymerase chain reaction., Results: Fifty-one failed DSAEK grafts from 50 eyes of 49 patients were identified. Indications for DSAEK were pseudophakic bullous keratopathy (28/51, 55%), Fuchs corneal endothelial dystrophy (12/51, 23%), failed penetrating keratoplasty (7/51, 14%), corneal decompensation from glaucoma (2/51, 4%), herpetic endotheliitis (1/51, 2%), and failed DSAEK (1/51, 2%). Forty-three grafts (83%) were primary DSAEK graft failure. HSV-1 DNA was isolated from 2 of 51 failed DSAEK grafts (4.0%). The corresponding corneoscleral donor rims did not demonstrate the presence of HSV-1., Conclusions: Based on our results, HSV-1 infection plays a minor role in DSAEK graft failure. The data suggest that recipient reactivation, rather than donor transmission, plays a role in HSV infection.

There are several pigmented nonneoplastic lesions that can clinically simulate melanocytic tumors. The authors report an unusual conjunctival epithelial inclusion cyst that contained luminal bacterial colonies, hemorrhage, and epithelial debris. Clinical appearance convincingly simulated a melanoma. The clinical and histopathologic features of this lesion are discussed.