Sex Differences in Dystonia.

BACKGROUND: Prior studies have indicated that female individuals outnumber male individuals for certain types of dystonia. Few studies have addressed factors impacting these sex differences or their potential biological mechanisms. OBJECTIVES: To evaluate factors underlying sex differences in the dystonias and explore potential mechanisms for these differences. METHODS: Data from individuals with various types of dystonia were analyzed in relation to sex. Data came from two different sources. One source was the Dystonia Coalition database, which contains predominantly idiopathic adult-onset focal and segmental dystonias. The second source was the MDSGene database, which contains predominantly early-onset monogenic dystonias. RESULTS: The 3222 individuals from the Dystonia Coalition included 71% female participants and 29% male participants for an overall female-to-male ratio (F:M) of 2.4. This ratio varied according to body region affected and whether dystonia was task-specific. The female predominance was age-dependent. Sex did not have a significant impact on co-existing tremor, geste antagoniste, depression or anxiety. In the 1377 individuals from the MDSGene database, female participants outnumbered male participants for some genes (GNAL, GCH1, and ANO3) but not for other genes (THAP1, TH, and TOR1A). CONCLUSIONS: These results are in keeping with prior studies that have indicated female individuals outnumber male individuals for both adult-onset idiopathic and early onset monogenic dystonias. These results extend prior observations by revealing that sex ratios depend on the type of dystonia, age, and underlying genetics.

Delirium is more common and associated with worse outcomes in Parkinson's disease compared to older adult controls: results of two prospective longitudinal cohort studies.

BACKGROUND: Inpatient prevalence of Parkinson's disease (PD) delirium varies widely across the literature. Delirium in general older populations is associated with adverse outcomes, such as increased mortality, dementia, and institutionalisation. However, to date there are no comprehensive prospective studies in PD delirium. This study aimed to determine delirium prevalence in hospitalised PD participants and the association with adverse outcomes, compared to a control group of older adults without PD. METHODS: Participants were hospitalised inpatients from the 'Defining Delirium and its Impact in Parkinson's Disease' and the 'Delirium and Cognitive Impact in Dementia' studies comprising 121 PD participants and 199 older adult controls. Delirium was diagnosed prospectively using the Diagnostic and Statistical Manual of Mental Disorders 5th Edition criteria. Outcomes were determined by medical note reviews and/or home visits 12 months post hospital discharge. RESULTS: Delirium was identified in 66.9% of PD participants compared to 38.7% of controls (p < 0.001). In PD participants only, delirium was associated with a significantly higher risk of mortality (HR = 3.3 (95% confidence interval [CI] = 1.3-8.6), p = 0.014) and institutionalisation (OR = 10.7 (95% CI = 2.1-54.6), p = 0.004) 12 months post-discharge, compared to older adult controls. However, delirium was associated with an increased risk of developing dementia 12 months post-discharge in both PD participants (OR = 6.1 (95% CI = 1.3-29.5), p = 0.024) and in controls (OR = 13.4 (95% CI = 2.5-72.6), p = 0.003). CONCLUSION: Delirium is common in hospitalised PD patients, affecting two thirds of patients, and is associated with increased mortality, institutionalisation, and dementia. Further research is essential to understand how to accurately identify, prevent and manage delirium in people with PD who are in hospital.

Remote area nurses' experiences of workplace safety in very remote primary health clinics: A qualitative study.

AIM: To explore Remote Area Nurses' experiences of the implementation of workplace health and safety policies and risk mitigation strategies in Australian very remote primary health clinics. DESIGN: This qualitative study used online semi-structured interviews, with participants purposively sampled to maximize variation in work location and service type. Data were analysed using a reflexive thematic analysis approach. Coding was carried out inductively, with NVivo 12 aiding data management. SETTING: The interviews were conducted from 24 Februrary 2021 to 06 March 2021 with Remote Area Nurses from very remote primary health clinics in Australia. PARTICIPANTS: Fifteen Remote Area Nurses participated in the study. RESULTS: Thematic analysis revealed varied approaches to workplace safety among the different health services and regions. While the spread of 'never alone' policies in many clinics addressed one of the significant risks faced by Remote Area Nurses, gaps remained even for hazards specifically highlighted in existing work health and safety legislation. Meaningful collaboration with staff and the community, local orientation, preparation for the role and providing quality care were protective factors for staff safety. Understaffing, unsafe infrastructure and inadequate equipment were common concerns among Remote Area Nurses. CONCLUSION: Health services need to prioritize workplace safety and take a continuous quality improvement approach to its implementation. This will include ensuring safety strategies are appropriate for the local context, improving infrastructure maintenance, and establishing sustainable second responder systems such as a pool of drivers with local knowledge. IMPLICATIONS FOR THE PROFESSION: Poor personal safety contributes to burnout and high turnover of staff. Nurses' insights into the barriers and enablers of current workplace safety strategies will aid policymakers and employers in future improvements. REPORTING METHOD: COREQ reporting guidelines were followed. PIPE STATEMENT: A panel of six Remote Area Nurses collaborated in the development of this project.

APOE ε4 positivity predicts centrality of episodic memory nodes in patients with mild cognitive impairment: A cohort-based, graph theory-informed study of cognitive networks.

As network neuroscience can capture the systemic impact of APOE variability at a neuroimaging level, this study investigated the network-based cognitive endophenotypes of ε4-carriers and non-carriers across the continuum between normal ageing and Alzheimer's dementia (AD). We hypothesised that the impact of APOE-ε4 on cognitive functioning can be reliably captured by the measurement of graph-theory centrality. Cognitive networks were calculated in 8118 controls, 3482 MCI patients and 4573 AD patients, recruited in the National Alzheimer's Coordinating Center (NACC) database. Nodal centrality was selected as the neurofunctional readout of interest. ε4-carrier-vs.-non-carrier differences were tested in two independent NACC sub-cohorts assessed with either Version 1 or Version 2 of the Uniform Data Set neuropsychological battery. A significant APOE-dependent effect emerged from the analysis of the Logical-Memory nodes in MCI patients in both sub-cohorts. While non-carriers showed equal centrality in immediate and delayed recall, the latter was significantly less central among carriers (v1: bootstrapped confidence interval 0.107-0.667, p < 0.001; v2: bootstrapped confidence interval 0.018-0.432, p < 0.001). This indicates that, in carriers, delayed recall was, overall, significantly more weakly correlated with the other cognitive scores. These findings were replicated in the sub-groups of sole amnestic-MCI patients (n = 2971), were independent of differences in network communities, clinical severity or other demographic factors. No effects were found in the other two diagnostic groups. APOE-ε4 influences nodal properties of cognitive networks when patients are clinically classified as MCI. This highlights the importance of characterising the impact of risk factors on the wider cognitive network via network-neuroscience methodologies.

An Empirical Comparison of Commonly Used Universal Rating Scales for Dystonia.

Background: There are several widely used clinical rating scales for documenting the severity and distribution of various types of dystonia. Objectives: The goal of this study was to evaluate the performance of the most commonly used scales in a large group of adults with the most common types of isolated dystonia. Methods: Global Dystonia Rating Scale (GDRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFM) scores were obtained for 3067 participants. Most had focal or segmental dystonia, with smaller numbers of multifocal or generalized dystonia. These scales were also compared for 209 adults with cervical dystonia that had Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) scores and 210 adults with blepharospasm that had Blepharospasm Severity Scale (BSRS) scores. Results: There were strong correlations between the GDRS and BFM total scores (r = 0.79) and moderate correlations for their sub scores (r > 0.5). Scores for both scales showed positive skew, with an overabundance of low scores. BFM sub-scores were not normally distributed, due to artifacts caused by the provoking factor. Relevant sub-scores of the GDRS and BFM also showed moderate correlations with the TWSTRS (r > 0.5) for cervical dystonia and the BSRS (r > 0.5) for blepharospasm. Conclusions: The BFM is more widely used than the GDRS, but these results suggest the GDRS may be preferable for focal and segmental dystonias. The overabundance of very low scores for both scales highlights challenges associated with discriminating very mild dystonia from other abnormal movements or variants of normal behavior.

Expanding the social cure: a mixed-methods approach exploring the role of online group dance as support for young people (aged 16-24) living with anxiety.

There is an increased interest in whether online arts interventions support mental health and social connections. This study explored eight weeks of online group dance as support for young people (aged 16-24) living with anxiety. The applicability of the 'social cure' theoretical framework to the novel context of an online dance class was sought. The study utilised an embedded QUAL+quan design, incorporating participatory focus group discussions (n = 3 groups; n = 11 participants) and one-on-one interviews (n = 2 participants), creative reflections (n = 16 participants) and ethnographic fieldnotes, and a repeated measures design with surveys at three timepoints (week 1, n = 27; week 4, n = 18; week 8, n = 14). Thematic analysis identified two overarching themes demonstrating how the dance classes (i) provided the opportunity to co-construct a meaningful shared identity and (ii) supported holistic wellbeing. The quantitative findings supported this, suggesting lower anxiety, depression, and loneliness and higher wellbeing, self-esteem, self-efficacy, and group closeness. This study expands the social cure to its application to an online dance context for the first time.

The effects of joint hypermobility on pain and functional biomechanics in adolescents with juvenile fibromyalgia: secondary baseline analysis from a pilot randomized controlled trial.

BACKGROUND: Joint hypermobility is a common clinical finding amongst hereditary connective tissue disorders that is observed in pediatric rheumatological settings, and often associated with chronic pain. Joint hypermobility may also contribute to deficits in physical functioning and physical activity, but previous findings have been inconsistent. It is possible that physical activity impairment in joint hypermobility may be due to chronic aberrant movement patterns subsequent to increased joint laxity. METHOD: As part of a larger randomized pilot trial of juvenile onset fibromyalgia (JFM), a secondary analysis was conducted to explore whether adolescents with JFM and joint hypermobility differed from non-joint hypermobility peers in terms of pain, daily functioning, and biomechanics (i.e., kinetics and kinematics) during a moderately vigorous functional task. RESULTS: From the larger sample of adolescents with JFM (N = 36), 13 adolescents (36.1%) met criteria for joint hypermobility and 23 did not have joint hypermobility. Those with joint hypermobility exhibited poorer overall functioning (Md = 20, Q1,Q3 [5.8, 7.6] vs. Md = 29, Q1,Q3 [5.1, 7.6]) but there were no differences in pain (Md = 6.9, Q1,Q3 [22, 33], vs. Md = 6.45, Q1,Q3 [15, 29.5]). Inspection of time-series plots suggests those with joint hypermobility exhibited decreased hip flexion and frontal plane hip moment (e.g., resistance to dynamic valgus) during the landing phase (early stance) and greater hip and knee transverse plane moments during the propulsion phase (late stance) of the drop vertical jump task (DVJ). No other differences in lower extremity biomechanics were observed between study groups. CONCLUSIONS: In this exploratory study, there were small but notable differences in biomechanics between patients with JFM who also had joint hypermobility versus those without joint hypermobility during a landing and jumping task (e.g., DVJ). These differences may indicate decreased joint stiffness during landing, associated with increased joint laxity and decreased joint stability, which may put them at greater risk for injury. Further study with a larger sample size is warranted to examine whether these biomechanical differences in patients with JFM and joint hypermobility affect their response to typical physical therapy or exercise recommendations.

Online 'chats': fostering communitas and psychosocial support for people working across arts and play for health and wellbeing.

Loss of work, furlough, and increased social isolation were prevalent for many working in the broad context of cultural and community engagement for health and wellbeing. This study set out to explore if and how regular online group interactions may foster social cohesion and provide support for these individuals during the critical time of the COVID-19 global pandemic. It was conducted in the context of the 'social cohesion chat' series led by a network called the Arts Play Health Community which was initiated in response to the pandemic as a way to bring those working in or connected to arts, play and health together during times of social isolation. Two qualitative focus groups with creative, participatory components were conducted with artists, researchers, evaluators, and arts/play managers (n = 11), and then analyzed using thematic analysis. Researcher ethnographic reflections and fieldnotes were also collected and analyzed. The authors engaged in reflexive online discussions to integrate and synthesize findings across different data. Four themes were constructed through the analysis procedure: (1) 'Building an online community as processes of communitas', spotlighting the importance of the non-hierarchical structure of the 'chats' particularly in relation to there being 'no end goal' to the online dialogues; (2) 'Individual and shared emotional experiences' that underpinned feelings of connection to others and the online space; (3) 'Psychosocial benefits' such as improving confidence and providing an opportunity to 'have a voice' in the community; and (4) 'The importance of facilitation', highlighting the opportunities the chats provided for participants to feel validated and valued as an active member of the community. The article concludes that constructing an inclusive and welcoming online community, where active participation is at the heart of regular social interactions can provide support for those working across arts and play for health and wellbeing. This was particularly important during the societal turbulence of the COVID-19 pandemic. It further concludes by noting the unique structure of these online dialogues as not being connected to institutions, with this playing a key role in allowing those in the community to 'be themselves' within it.

Structural racism and geographic access to food retailers in the United States: A scoping review.

This scoping review summarized findings and key measures from U.S.-based studies that 1) examined associations between geographic indicators of structural racism (e.g., redlining, racial segregation) and access to food retailers (e.g., supermarkets, convenience stores) or 2) documented disparities in access by neighborhood racial/ethnic composition. In 2022, relevant scientific literature was reviewed using Covidence software. Independent reviewers examined 13,069 citations; 163 citations advanced to the full-text review stage and 70 were selected for inclusion. Twenty-one studies (30%) linked one or more indicator of structural racism to food retailer access while 49 (70%) solely examined differences in access by neighborhood racial/ethnic composition. All studies featuring indicators of structural racism reported significant findings; however, indicators varied across studies making it difficult to make direct comparisons. Key indicators of structural racism in the food access literature included redlining (n = 3), gentrification (n = 3), and racial segregation (n = 4). Many U.S.-based studies have evaluated food retailer access by neighborhood racial/ethnic composition. Moving forward, studies should model indicators of structural racism and determine their influence on geographic access to large and small food retailers.

Predicting cognitive decline using neuropsychiatric symptoms in prodromal Lewy body dementia: A longitudinal study.

INTRODUCTION: Neuropsychiatric symptoms (NPS) in Lewy body dementias (LBD) occur frequently and early in disease progression. Such symptoms are associated with worse quality of life, caregiver burden and functional limitations. Limited evidence exists, however, outlining the longitudinal relationship between NPS and cognitive decline in prodromal LBD. METHODS: 123 participants were derived from three cohort studies. Patients with mild cognitive impairment (MCI) relating to probable dementia with Lewy bodies (MCI-LB, n = 67) and Parkinson's disease (PD-MCI, n = 56) completed comprehensive cognitive and neuropsychiatric assessment and were followed up longitudinally. Linear regression and mixed effects models assessed the relationship between baseline NPS and cognition at baseline and over time. RESULTS: In MCI-LB, overall NPS burden was associated with declines over time in executive function (p = 0.026) and processing speed (p = 0.028) and baseline aberrant motor behaviour was associated with declines in attention (p < 0.025). Anxiety was significantly associated with poorer visuospatial functioning (p = 0.016) at baseline and poorer attention both at baseline (p = 0.017) and across time points (p = 0.024). In PD-MCI, psychosis was associated with poorer executive functioning at baseline (p = 0.008) and across time points (p = 0.002) but had no association with changes longitudinally. CONCLUSIONS: Core neuropsychiatric components of LBD are not strongly associated with cognition in prodromal disease. This may suggest that neuropathological mechanisms underlying NPS may not be the same as those underlying cognitive impairment. Non-core NPS, however, may be more directly associated with cognitive change. Future studies utilising neuroimaging techniques are needed to explore the neuropathological basis of NPS in prodromal LBD.

Zoledronic acid improves bone quality and muscle function in a high bone turnover state.

SUMMARY: Zoledronic acid (ZA) prevents muscle weakness in mice with bone metastases; however, its role in muscle weakness in non-tumor-associated metabolic bone diseases and as an effective treatment modality for the prevention of muscle weakness associated with bone disorders, is unknown. We demonstrate the role of ZA-treatment on bone and muscle using a mouse model of accelerated bone remodeling, which represents the clinical manifestation of non-tumor associated metabolic bone disease. ZA increased bone mass and strength and rescued osteocyte lacunocanalicular organization. Short-term ZA treatment increased muscle mass, whereas prolonged, preventive treatment improved muscle mass and function. In these mice, muscle fiber-type shifted from oxidative to glycolytic and ZA restored normal muscle fiber distribution. By blocking TGFß release from bone, ZA improved muscle function, promoted myoblast differentiation and stabilized Ryanodine Receptor-1 calcium channel. These data demonstrate the beneficial effects of ZA in maintaining bone health and preserving muscle mass and function in a model of metabolic bone disease. Context and significance: TGFß is a bone regulatory molecule which is stored in bone matrix, released during bone remodeling, and must be maintained at an optimal level for the good health of the bone. Excess TGFß causes several bone disorders and skeletal muscle weakness. Reducing excess TGFß release from bone using zoledronic acid in mice not only improved bone volume and strength but also increased muscle mass, and muscle function. Progressive muscle weakness coexists with bone disorders, decreasing quality of life and increasing morbidity and mortality. Currently, there is a critical need for treatments improving muscle mass and function in patients with debilitating weakness. Zoledronic acid's benefit extends beyond bone and could also be useful in treating muscle weakness associated with bone disorders.

Examining the associations between physical activity, self-esteem, perceived stress, and internalizing symptoms among older adolescents.

INTRODUCTION: In older adolescence, stress has been found to be prevalent. It has been seen that higher physical activity (PA) relates to lower stress levels, which, in turn, relates to fewer anxiety and depressive symptoms (internalizing symptoms). However, how these associations function is not fully understood. PA is strongly associated with greater self-esteem in adolescents. As greater self-esteem is thought to aid better coping with stress and has been seen as beneficial for mental health in adolescents, PA may be associated with lower stress and better mental health through self-esteem and more adaptive stress appraisals. Therefore, the aim of the study was to examine the relationships between PA, self-esteem, stress, and mental health. METHODS: A cross-sectional design was employed, and path analysis was implemented. PA, self-esteem, stress appraisals, distress tolerance, perceived stress, anxiety, and depression were assessed using online questionnaires from 244 adolescent participants from the United Kingdom (aged 15-19, M = 16.75 [SD = 0.82], 145 female). RESULTS: Path analysis revealed that PA was associated with lower perceived stress through increased self-esteem, adaptive appraisals, and higher distress tolerance (total standardized indirect effect; p = .007 (-0.25 to -0.11). Moreover, lower perceived stress was associated with lower anxiety (standardized direct effect; p < .001 [2.65-4.0] and depressive symptoms (standardized direct effect; p < .001 [0.33-0.63]). CONCLUSIONS: Findings suggest that higher PA could be effective in improving mental health among older adolescents, due to its association with perceived stress through higher self-esteem and more adaptive appraisals of stress.

Current Understanding of Verbal Fluency in Alzheimer's Disease: Evidence to Date.

Since their development, verbal fluency tests (VFTs) have been used extensively throughout research and in clinical settings to assess a variety of cognitive functions in diverse populations. In Alzheimer's disease (AD), these tasks have proven particularly valuable in identifying the earliest forms of cognitive decline in semantic processing and have been shown to relate specifically to brain regions associated with the initial stages of pathological change. In recent years, researchers have developed more nuanced techniques to evaluate verbal fluency performance, extracting a wide range of cognitive metrics from these simple neuropsychological tests. Such novel techniques allow for a more detailed exploration of the cognitive processes underlying successful task performance beyond the raw test score. The versatility of VFTs and the richness of data they may provide, in light of their low cost and speed of administration, therefore, highlight their potential value both in future research as outcome measures for clinical trials and in a clinical setting as a screening measure for early detection of neurodegenerative diseases.

Low-Magnitude Mechanical Signals Combined with Zoledronic Acid Reduce Musculoskeletal Weakness and Adiposity in Estrogen-Deprived Mice.

Combination treatment of Low-Intensity Vibration (LIV) with zoledronic acid (ZA) was hypothesized to preserve bone mass and muscle strength while reducing adipose tissue accrual associated with complete estrogen (E 2 )-deprivation in young and skeletally mature mice. Complete E 2 -deprivation (surgical-ovariectomy (OVX) and daily injection of aromatase inhibitor (AI) letrozole) were performed on 8-week-old C57BL/6 female mice for 4 weeks following commencement of LIV administration or control (no LIV), for 28 weeks. Additionally, 16-week-old C57BL/6 female E 2 -deprived mice were administered ±LIV twice daily and supplemented with ±ZA (2.5 ng/kg/week). By week 28, lean tissue mass quantified by dual-energy X-ray absorptiometry was increased in younger OVX/AI+LIV(y) mice, with increased myofiber cross-sectional area of quadratus femorii. Grip strength was greater in OVX/AI+LIV(y) mice than OVX/AI(y) mice. Fat mass remained lower in OVX/AI+LIV(y) mice throughout the experiment compared with OVX/AI(y) mice. OVX/AI+LIV(y) mice exhibited increased glucose tolerance and reduced leptin and free fatty acids than OVX/AI(y) mice. Trabecular bone volume fraction and connectivity density increased in the vertebrae of OVX/AI+LIV(y) mice compared to OVX/AI(y) mice; however, this effect was attenuated in the older cohort of E 2 -deprived mice, specifically in OVX/AI+ZA mice, requiring combined LIV with ZA to increase trabecular bone volume and strength. Similar improvements in cortical bone thickness and cross-sectional area of the femoral mid-diaphysis were observed in OVX/AI+LIV+ZA mice, resulting in greater fracture resistance. Our findings demonstrate that the combination of mechanical signals in the form of LIV and anti-resorptive therapy via ZA improve vertebral trabecular bone and femoral cortical bone, increase lean mass, and reduce adiposity in mice undergoing complete E 2 -deprivation. One Sentence Summary: Low-magnitude mechanical signals with zoledronic acid suppressed bone and muscle loss and adiposity in mice undergoing complete estrogen deprivation. Translational Relevance: Postmenopausal patients with estrogen receptor-positive breast cancer treated with aromatase inhibitors to reduce tumor progression experience deleterious effects to bone and muscle subsequently develop muscle weakness, bone fragility, and adipose tissue accrual. Bisphosphonates (i.e., zoledronic acid) prescribed to inhibit osteoclast-mediated bone resorption are effective in preventing bone loss but may not address the non-skeletal effects of muscle weakness and fat accumulation that contribute to patient morbidity. Mechanical signals, typically delivered to the musculoskeletal system during exercise/physical activity, are integral for maintaining bone and muscle health; however, patients undergoing treatments for breast cancer often experience decreased physical activity which further accelerates musculoskeletal degeneration. Low-magnitude mechanical signals, in the form of low-intensity vibrations, generate dynamic loading forces similar to those derived from skeletal muscle contractility. As an adjuvant to existing treatment strategies, low-intensity vibrations may preserve or rescue diminished bone and muscle degraded by breast cancer treatment.

Nutritional markers accompanying acquired chylothorax in infants: a systematic review.

CONTEXT: Chylothorax is a well-established acquired complication of thoracic surgery in infants. Current data suggest acquired chylothorax may affect infant growth and nutrition because of a loss of essential nutrients via chylous effusion. OBJECTIVE: The 3 objectives for this study were: (1) identify nutritional markers affected by the development of acquired chylothorax in infants; (2) highlight the variability in methods used to assess nutritional status and growth in this patient population; and (3) highlight nutritional deficits that can serve as treatment targets during postoperative feeding protocols. DATA SOURCES: A systematic literature search was conducted between May 31, 2021, and June 21, 2022, using the PubMed, Embase, CINAHL, and Web of Science databases. Search terms included, but were not limited to, "chylothorax," "infants," and "nutrition." DATA EXTRACTION: Inclusion criteria required studies that measured quantitative markers of nutrition in ≥10 participants aged <1 year with acquired chylothorax. A total of 575 studies were screened and all but 4 were eliminated. Nutritional markers were categorized into 4 different groups: total serum protein level, triglyceride levels, growth velocity, and weight for length. DATA ANALYSIS: The variation in methods, time points, interventional groups, and nutritional markers did not facilitate a meta-analysis. Risk of bias was assessed using the Cochrane Risk of Bias in Nonrandomized Studies assessment tool. CONCLUSION: This review highlights the need for reliable quantitative markers of nutrition that will enable providers to assess the nutritional needs of infants with chylothorax. Future studies must focus on measuring markers of nutrition at regular intervals in larger study populations.

Verbal fluency discrepancies as a marker of the prehippocampal stages of Alzheimer's disease.

OBJECTIVE: Prior to evidence of episodic memory decline, a lengthy preclinical phase of Alzheimer's disease (AD) exists characterized by the build-up of tau pathology within extrahippocampal structures. Semantic memory, also impaired in AD, has been linked to degradation within these earliest affected areas. This study aimed to assess the utility of performance discrepancies between letter and category verbal fluency tasks to detect neuronal loss in brain regions affected very early by AD. METHOD: Whole-brain voxel-based morphometry was used to assess the neural correlates of semantic processing in three patient groups: two groups of mild cognitive impairment (MCI) patients split into mildly (n = 58) and moderately (n = 53) affected and a mild AD dementia group (n = 71). Discrepancies between the level of impairment on the semantic category fluency test and nonsemantic letter fluency test were calculated for each participant and included in regression models measuring the relationship between semantic memory and whole-brain gray matter volume. RESULTS: Patients at all disease stages demonstrated a loss of the normal semantic advantage in fluency tests, showing significantly greater impairments in category relative to letter fluency. Discrepancy scores in mild MCI correlated strongly with the structural integrity of the anterior medial temporal lobes. Correlations in more severely affected groups were weaker and more widespread. CONCLUSIONS: Semantic memory appears a useful indicator of even the earliest stages of medial temporal damage in AD. With advancing disease severity, the discrepancy index loses its focal anatomical association, reinforcing its value as an early marker of incipient decline. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Impact of prenatal opioids on cardiac and autonomic development: systematic review and meta-analysis.

Prenatal opioid exposure has recently risen four-fold with limited data on the developmental effects on neonatal physiology. The objective of this systematic review is to develop an association between prenatal opioid exposure and fetal and neonatal cardiac and autonomic development and function. The review was conducted in accordance with PRISMA Guidelines, and searches were conducted using PubMed, Embase, CINAHL, and Web of Science between May 25 and October 27, 2020. Twenty studies fit inclusion criteria, in four categories: (1) fetal cardiac outcomes, (2) neonatal cardiac outcomes, (3) noninvasive autonomic outcomes, and (4) clinical and behavioral measures. For the meta-analysis, three studies (total of 210 subjects) were included. Effect sizes were measured as the mean difference in fetal heart rate between opioid-exposed and non-exposed groups. Mothers with prenatal opioid use had a significantly lower fetal heart rate as compared to mothers without prenatal opioid use, requiring further studies to determine clinical significance.

Workforce safety in the remote health sector of Australia: a scoping review.

OBJECTIVES: To scope the evidence surrounding workplace health and safety risks for the remote health workforce in Australia and to collate the recommendations to address those risks. DESIGN: A five-stage scoping review framework refined by Cooper et al was used for this review. Informit Health Collection, Ovid Emcare, Medline, Web of Science Core Collection, ProQuest and the grey literature were searched in October 2020 using a combination of key words derived from the eligibility criteria. No date restriction was placed on the search. Title and abstract screening, full-text review and data extraction were performed by three reviewers. Data were analysed by the lead author using qualitative thematic analysis. ELIGIBILITY CRITERIA: Articles were eligible for inclusion if they were published research or industry reports, focused on safety for the remote health workforce in Australia, identified hazards/safety risks or recommendations to reduce risk, and were written in English. RESULTS: The search yielded 312 articles, of which 18 met the inclusion criteria. A wide range of hazards/safety risks and recommendations were identified within the literature, which related to safety culture, isolation, safe environment, and education and training. Some recommendations, such as the use of a risk management approach, good post-incident support, safer clinics and accommodation, and improved access to education and training, had been discussed in the literature for over a decade, with a high level of agreement regarding their importance. Two articles briefly evaluated the impact of some recommendations. CONCLUSION: While many recommendations have been developed to improve the safety of the remote health workforce in Australia, there is little evidence of their implementation and evaluation. As many remote health professionals report ongoing or worsening workplace safety issues, there is an urgent need for the implementation and evaluation of the workforce safety strategies recommended in the literature and required by legislation.

Cerebrospinal fluid cytokine, chemokine, and SARS-CoV-2 antibody profiles in children with neuropsychiatric symptoms associated with COVID-19.

BACKGROUND: Neuropsychiatric symptoms and CSF cytokine, chemokine, and SARS-COV-2 antibody profiles are unknown in pediatric patients with COVID-19 or multisystem inflammatory syndrome (MIS-C), (NP-COVID-19). METHODS: Children at a single pediatric institution quaternary referral center with laboratory-confirmed COVID-19 or MIS-C and neuropsychiatric symptoms were included in this retrospective case series. Clinical symptoms, ancillary testing data, treatments and outcomes are described. Multiplexed electrochemiluminescence assays for cytokines, chemokines and SARS-CoV-2 antibodies were tested in the CSF NP-COVID-19 patients compared to five controls and were analyzed using the Student's t-test. RESULTS: Three of five NP-COVID-19 patients had psychiatric symptoms, and two patients had encephalopathy and seizures. All patients had full or near resolution of neuropsychiatric symptoms by discharge. One patient received intravenous steroids for treatment for psychiatric symptoms; 3/5 other patients received immunotherapy for MIS-C, including IVIG, high-dose steroids, anakinra, and tocilizumab. Pro-inflammatory chemokines, including MIG, MPC, MIP-1ß, and TARC were significantly elevated in NP-COVID-19 patients compared to controls. Two of five patients had elevated CSF neurofilament light chain. CSF SARS-CoV-2 antibody titers to the full-length spike, receptor binding domain and N-terminal domain were significantly elevated. SARS-CoV-2 antibody titers strongly correlated with pro-inflammatory chemokines/cytokines, including IL-1ß, IL-2, IL-8, TNF-α, and IFN-γ (P≤0.05 for all). CONCLUSIONS: A spectrum of neuropsychiatric clinical manifestations can occur in children with SARS-CoV-2 infection. CSF pro-inflammatory chemokines and SARS-CoV-2 antibodies may serve as biomarkers of SARS-CoV-2 mediated NP-COVID-19. Additional study is required to understand the pathophysiologic mechanisms of neuroinflammation in children with COVID-19 and MIS-C.

A Graph Theory Approach to Clarifying Aging and Disease Related Changes in Cognitive Networks.

In accordance with the physiological networks that underlie it, human cognition is characterized by both the segregation and interdependence of a number of cognitive domains. Cognition itself, therefore, can be conceptualized as a network of functions. A network approach to cognition has previously revealed topological differences in cognitive profiles between healthy and disease populations. The present study, therefore, used graph theory to determine variation in cognitive profiles across healthy aging and cognitive impairment. A comprehensive neuropsychological test battery was administered to 415 participants. This included three groups of healthy adults aged 18-39 (n = 75), 40-64 (n = 75), and 65 and over (n = 70) and three patient groups with either amnestic (n = 75) or non-amnestic (n = 60) mild cognitive impairment or Alzheimer's type dementia (n = 60). For each group, cognitive networks were created reflective of test-to-test covariance, in which nodes represented cognitive tests and edges reflected statistical inter-nodal significance (p < 0.05). Network metrics were derived using the Brain Connectivity Toolbox. Network-wide clustering, local efficiency and global efficiency of nodes showed linear differences across the stages of aging, being significantly higher among older adults when compared with younger groups. Among patients, these metrics were significantly higher again when compared with healthy older controls. Conversely, average betweenness centralities were highest in middle-aged participants and lower among older adults and patients. In particular, compared with controls, patients demonstrated a distinct lack of centrality in the domains of semantic processing and abstract reasoning. Network composition in the amnestic mild cognitive impairment group was similar to the network of Alzheimer's dementia patients. Using graph theoretical methods, this study demonstrates that the composition of cognitive networks may be measurably altered by the aging process and differentially impacted by pathological cognitive impairment. Network alterations characteristic of Alzheimer's disease in particular may occur early and be distinct from alterations associated with differing types of cognitive impairment. A shift in centrality between domains may be particularly relevant in identifying cognitive profiles indicative of underlying disease. Such techniques may contribute to the future development of more sophisticated diagnostic tools for neurodegenerative disease.