Translating pH-sensitive PROgressive saturation for QUantifying Exchange rates using Saturation Times (PRO-QUEST) MRI to a 3T clinical scanner.

PURPOSE: To translate the recently developed PRO-QUEST (Progressive saturation for quantifying exchange rates using saturation times) sequence from preclinical 9.4T to 3T clinical magnetic field strength. METHODS: Numerical simulations were performed to define the optimal saturation flip angles for PRO-QUEST saturation pulses at 3T and demonstrate the effect of a ∆T2 error on the exchange rate (kex ) estimation at various field strengths. Exchange-dependent relaxation rate (Rex ) was measured for glutamate solutions in various pH, healthy volunteers and patients with multiple sclerosis (MS). Additionally, concentration-independent ratiometric Rex maps were produced to evaluate regional signal variations across the brain of human volunteers. RESULTS: The calculated Rex significantly correlates with pH in glutamate samples, however, kex values are underestimated as compared to those previously obtained at 9.4T. In the ratiometric Rex map of healthy volunteers, no significant differences are found between grey matter, white matter, and basal ganglia. In patients with MS, white matter lesions are visible in single saturation power Rex maps whereas only a periventricular lesion is apparent in the ratiometric Rex map. CONCLUSION: We demonstrate that quantification of pH sensitive indices using PRO-QUEST is feasible at 3T within clinically acceptable acquisition times. Our initial findings in patients with MS show that pH sensitive indices varied with the type of lesion examined whereas no significant difference was found in healthy volunteers between tissue types, suggesting that it would be worthwhile to apply PRO-QUEST in a larger cohort of patients to better understand its distinct imaging features relative to conventional techniques.

PET/CT imaging of prostate cancer in the era of small molecule prostate specific membrane antigen targeted tracers.

Staging and restaging of prostate cancer is crucial for treatment planning and prognosis. Accurate localization is of high relevance for a tailor-made therapy and an early detection of unknown metastatic spread can lead to a survival benefit. Evidence based guidelines that are currently in use were established using data from conventional imaging (such as magnetic resonance imaging (MRI), computed tomography (CT) and bone scintigraphy). Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is rapidly evolving with promising results. However, up to now there is little consensus about the usefulness of this method, especially since different guidelines are "biased" depending on the association that shapes them. Firstly, little data exists on the staging of low risk tumors and probably PSMA PET/CT should be avoided in this setup for most patients. On the other hand, it has been recently proven that PSMA PET/CT can replace CT and bone scintigraphy (combined) in staging of advanced prostate cancer. Furthermore, the examination gained general acceptance through its excellent performance in biochemical recurrence, both for castration naïve and castration resistant tumors, and should be implemented where available. It is undisputed that PSMA PET/CT provides a more accurate picture of prostate cancer patients and can lead to both upstaging and downstaging, thus affecting therapeutic management. Though it is not clear yet if the more accurate staging will lead to better therapeutic decisions and improve patient outcomes, PSMA PET/CT appears as the next imaging standard for prostate cancer for the years to come.

PRO-QUEST: a rapid assessment method based on progressive saturation for quantifying exchange rates using saturation times in CEST.

PURPOSE: To develop a new MRI technique to rapidly measure exchange rates in CEST MRI. METHODS: A novel pulse sequence for measuring chemical exchange rates through a progressive saturation recovery process, called PRO-QUEST (progressive saturation for quantifying exchange rates using saturation times), has been developed. Using this method, the water magnetization is sampled under non-steady-state conditions, and off-resonance saturation is interleaved with the acquisition of images obtained through a Look-Locker type of acquisition. A complete theoretical framework has been set up, and simple equations to obtain the exchange rates have been derived. RESULTS: A reduction of scan time from 58 to 16 minutes has been obtained using PRO-QUEST versus the standard QUEST. Maps of both T1 of water and B1 can simply be obtained by repetition of the sequence without off-resonance saturation pulses. Simulations and calculated exchange rates from experimental data using amino acids such as glutamate, glutamine, taurine, and alanine were compared and found to be in good agreement. The PRO-QUEST sequence was also applied on healthy and infarcted rats after 24 hours, and revealed that imaging specificity to ischemic acidification during stroke was substantially increased relative to standard amide proton transfer-weighted imaging. CONCLUSION: Because of the reduced scan time and insensitivity to nonchemical exchange factors such as direct water saturation, PRO-QUEST can serve as an excellent alternative for researchers and clinicians interested to map pH changes in vivo.

QUESP and QUEST revisited - fast and accurate quantitative CEST experiments.

PURPOSE: Chemical exchange saturation transfer (CEST) NMR or MRI experiments allow detection of low concentrated molecules with enhanced sensitivity via their proton exchange with the abundant water pool. Be it endogenous metabolites or exogenous contrast agents, an exact quantification of the actual exchange rate is required to design optimal pulse sequences and/or specific sensitive agents. METHODS: Refined analytical expressions allow deeper insight and improvement of accuracy for common quantification techniques. The accuracy of standard quantification methodologies, such as quantification of exchange rate using varying saturation power or varying saturation time, is improved especially for the case of nonequilibrium initial conditions and weak labeling conditions, meaning the saturation amplitude is smaller than the exchange rate (γB1 < k). RESULTS: The improved analytical 'quantification of exchange rate using varying saturation power/time' (QUESP/QUEST) equations allow for more accurate exchange rate determination, and provide clear insights on the general principles to execute the experiments and to perform numerical evaluation. The proposed methodology was evaluated on the large-shift regime of paramagnetic chemical-exchange-saturation-transfer agents using simulated data and data of the paramagnetic Eu(III) complex of DOTA-tetraglycineamide. CONCLUSIONS: The refined formulas yield improved exchange rate estimation. General convergence intervals of the methods that would apply for smaller shift agents are also discussed. Magn Reson Med 79:1708-1721, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Stress and gender effects on prefrontal cortex oxygenation levels assessed during single and dual-task walking conditions.

The ability to walk is critical for functional independence and wellbeing. The pre-frontal cortex (PFC) plays a key role in cognitive control of locomotion, notably under attention-demanding conditions. Factors that influence brain responses to cognitive demands of locomotion, however, are poorly understood. Herein, we evaluated the individual and combined effects of gender and perceived stress on stride velocity and PFC Oxygenated Hemoglobin (HbO2 ) assessed during single and dual-task walking conditions. The experimental paradigm included Normal Walk (NW); Cognitive Interference (Alpha); and Walk-While-Talk (WWT) tasks. An instrumented walkway was used to assess stride velocity in NW and WWT conditions. Functional Near-Infrared-Spectroscopy (fNIRS) was used to quantify PFC HbO2 levels during NW, Alpha and WWT. Perceived task-related stress was evaluated with a single 11-point scale item. Participants were community residing older adults (age = 76.8 ± 6.7 years; %female = 56). Results revealed that higher perceived stress was associated with greater decline in stride velocity from single to dual-task conditions among men. Three-way interactions revealed that gender moderated the effect of perceived stress on changes in HbO2 levels comparing WWT to NW and Alpha. Attenuation in the increase in HbO2 levels, in high compared to low perceived stress levels, from the two single task conditions to WWT was observed only in men. Thus, older men may be more vulnerable to the effect of perceived stress on the change in PFC oxygenation levels across walking conditions that vary in terms of cognitive demands. These findings confer important implications for assessment and treatment of individuals at risk of mobility impairments.

Mild Cognitive Impairments Moderate the Effect of Time on Verbal Fluency Performance.

OBJECTIVES: Mild cognitive impairments (MCI) is a transitional state in aging associated with increased risk of incident dementia. The current study investigated whether MCI status moderated the effect of time on word generation during verbal fluency tasks. Specifically, the objective was to determine whether MCI status had differential effects on initial automatic or latter more effortful retrieval processes of fluency tasks. METHODS: Participants were community residing older adults enrolled in a longitudinal cohort study. Of the 408 participants, 353 were normal (age=76.06±6.61; %female=57.8) and 55 were diagnosed with MCI (age=78.62±7.00; %female=52.7). Phonemic and category fluency were each administered for 60 s, but performance was recorded at three consecutive 20-s intervals (0-20 s [T1], 21-40 s [T2], 41-60 s [T3]. Separate linear mixed effects models for each fluency task were used to determine the effects of group, time, and their interaction on word generation. RESULTS: In both fluency tasks, word generation declined as a function of time. Individuals with MCI generated fewer words compared to controls during the first 20 s of phonemic (beta=-1.56; p<.001; d=0.28) and category fluency (beta=-1.85; p<.001; d=0.37). Group by time interactions revealed that individuals with MCI demonstrated attenuated declines in word generation from the first to the second and third time intervals of both phonemic ([T1 vs. T2] beta=2.17, p=.001; d=0.41; [T1 vs. T3]beta=2.28, p=.001; d=0.45) and category ([T1 vs. T2] beta= 2.22, p=.002; d=0.50; [T1 vs. T3]beta=3.16, p<.001; d=0.71) fluency. CONCLUSIONS: Early automatic retrieval processes in verbal fluency tasks are compromised in MCI. (JINS, 2017, 23, 44-55).

Adjustment and homesickness in hospitalised children: A systematic review.

Children can experience significant distress during hospitalisation, as a result of the treatment process and due to psychosocial factors impacting their adjustment to the hospital environment. Such factors can contribute to negative outcomes for the child. Despite this, limited research focus has been placed on understanding the psychosocial factors that contribute to a child's distress to inform support strategies that can improve the experience of hospitalisation across paediatric conditions. The objectives of this review were to synthesise the qualitative and quantitative literature on psychosocial factors associated with hospital adjustment and to identify risk and protective factors that influence the adjustment process. The literature search (1980 to February 2024: CINAHL / Embase / Medline / PsychINFO and Web of Science databases) identified thirty-four studies. Poor hospital adjustment, anxiety, depression and homesickness, were reported by the majority of hospitalised children. Several demographic and psychosocial factors were identified in the quantitative synthesis to contribute to poor adjustment. Child age, temperament, attachment style, past negative hospital experiences, homesickness and fear cognitions, were all associated with adjustment to the hospital environment. Homesickness was identified as a particularly understudied and important construct. Theoretical and methodological considerations are discussed, and recommendations made for future research that can further support inpatient children and their families.

Child characteristics and health conditions associated with paediatric hospitalisations and length of stay: a population-based study.

Background: Paediatric hospital length of stay (LoS) is often used as a benchmark for resource use of hospitalisations. Previous studies have mostly focused on LoS of admissions for specific conditions or medical specialties. We aimed to conduct an evaluation of LoS of all paediatric hospitalisations exploring the frequency and characteristics; and associated childhood conditions. Methods: This population-based cross-sectional study included all hospital admissions in children aged <16 years between January 2017 and December 2019 in New South Wales, Australia. LoS was categorised into: day or overnight stay, 2-7, 8-21 and ≥ 22 days. Socio-demographic and health service characteristics of each individual admission by LoS and age groups were evaluated. Findings: A total of 324,083 children had 518,768 admissions comprising 1,064,032 bed days. Most admissions wereday/overnight stays (71.9%) or 2-7 days (25.3%). While LoS >7 days represented 2.8% of total admissions, they accounted for 27% of total bed days. Children aged 1-4 years had the highest proportion of admissions (35%), with a majority lasting ≤7 days, whereas 45.6% of admissions ≥22 days were for children aged ≥12 years. Respiratory conditions, diseases of the digestive system and traumatic injuries were the most common reasons for hospitalization. LoS >7 days were more common in children from most disadvantaged backgrounds, residing further from hospital and those aged ≥12 years with mental health conditions. Interpretation: The majority of paediatric hospitalizations are for short stay and require programs that target acute conditions that can be managed in primary care. Interventions such as care coordination, tailored models of care and enhanced outpatient/community treatment programs for high-risk groups will help reduce extended LoS and improving child health and well-being. Funding: Australian National Health and Medical Research Council.

Mental health concerns in children with neurodevelopmental conditions attending a developmental assessment service.

Children with neurodevelopmental conditions (NDCs), such as autism and attention-deficit/hyperactivity disorder (ADHD), frequently experience co-occurring mental health concerns. Little research has examined mental health symptoms in children attending developmental assessment services. This study profiled mental health symptoms in children with NDCs attending a hospital-based diagnostic service for their first diagnostic and developmental assessment. Participants were 232 children aged 1.96-17.51 years. Mental health concerns were assessed using the Child Behavior Checklist (CBCL), a caregiver-rated, questionnaire-based assessment of behavioural and emotional difficulties. Subclinical or clinically elevated internalising, externalising and total scores on the CBCL were reported in approximately 48% of preschool and 61% of school-age children. These increased prevalence rates, using the same cutoff scores, remained after excluding items specifically relating to neurodevelopmental concerns (36% preschool; 37% school-age children). More school-aged females reported elevated internalising problems, relative to males (67 % vs 48 %). The number of diagnoses impacted symptoms, with children who received two or more DSM-5 diagnoses showing a greater rate of subclinical or clinically elevated scores, relative to children who received one DSM-5 diagnosis. Our findings demonstrate that children attending developmental assessment services have considerable mental health needs. It is critical that mental health concerns are identified and addressed in children when they first present to developmental assessment services, and that service providers are equipped to provide appropriate resources and pathways to ongoing care.

Understanding the vocational functioning of autistic employees: the role of disability and mental health.

PURPOSE: Employment rates for autistic people are low, despite increasing employment-focused programmes. Given the reported complexities for autistic people in finding and keeping work and flourishing there, further exploration is needed to understand how best to help employers accommodate autistic employees. MATERIAL AND METHODS: We assessed 88 employed autistic adults, without comorbid intellectual disability and examined whether self-reported disability and mental health symptoms were associated with two measures of vocational functioning: disability days off work and vocational disability. RESULTS: Nearly half (47%) reported at least one disability day absence in the previous month. Autism severity and IQ were not associated with either measure of vocational functioning. Greater disability and higher mental health symptoms were associated with both types of vocational functioning. However, the associations of anxiety and stress with both vocational outcomes were attenuated to null in a multivariable model. Disability (B = 6.74, p = 0.009; B = 1.18, p < 0.001) and depression (B = 4.46, p = 0.035; B = 1.01, p = 0.049) remained independently associated with both outcomes. CONCLUSIONS: Clinicians and vocational support programmes addressing modifiable factors may need to focus on addressing mental health comorbidities, specifically depression rather than anxiety, or core features of autism to improve vocational outcomes for autistic people. Implications for RehabilitationIndividual-level interventions that reduce disablement, particularly in social areas, and depressive symptoms as a way of reducing days off work and improving workplace activities in autistic employees are recommended.Organisations can accommodate autistic employees by encouraging use of mental health programmes or looking at how the workplace environment can be adapted to limit social disability.

Burden of paediatric hospitalisations to the health care system, child and family: a systematic review of Australian studies (1990-2022).

Background: Paediatric hospitalisations represent a significant cost to the health system and cause significant burden to children and their families. Understanding trends in hospitalisation costs can assist with health planning and support strategies across stakeholders. The objective of this systematic review is to examine the trends in costs and burden of paediatric hospitalisations in Australia to help inform policy and promote the well-being of children and their families. Methods: Electronic data sources (Embase, Medline, Web of Science, PSYCH-Info, CINAHL and Scopus) were searched from 1990 until December 2022. Any quantitative or qualitative studies conducted in Australian tertiary hospitals were included in the review. Eligible studies were those that included paediatric (<18 years) hospitalisations and reported on economic and/or non-economic costs for the child, family unit and/or health system. Study quality and risk of bias for each study were assessed with the Joanna Briggs Critical Appraisal Tools. We present a summary of the findings of the hospitalisation burden across major diagnostic admission categories and for the child and family unit. The systematic review was registered with Prospero (ID: CRD42021276202). Findings: The review summarises a total of 88 studies published between 1990 and December 2022. Overall, the studies identified that paediatric hospitalisations incur significant financial costs, which have not shown significant reductions over time. In-patient direct hospital costs varied depending on the type of treatment and diagnostic condition. The costs per-case were found to range from just below AUD$2000 to AUD$20,000 or more. The financial burden on the family unit included loss of productivity, transport and travel costs. Some studies reported estimates of these costs upward of AUD$500 per day. Studies evaluating 'hospital in the home' options identified significant benefits in reducing hospitalisations and costs without compromising care. Interpretation: Increasing focus on alternative models of care may help alleviate the significant costs associated with paediatric hospitalisation. Funding: This research was supported by Hospitals United for Sick Kids (formerly Curing Homesickness).

Lead contamination of soils, sediments, and vegetation in a shooting range and adjacent terrestrial and aquatic ecosystems: A holistic approach for evaluating potential risks.

It is well accepted that shooting ranges constitute hotspots of Pb contamination. This study evaluated the degree of Pb contamination of soils, sediments and vegetation within the boundaries of a highly visited shooting range, as well as the fluvial transport and dispersal of Pb, and therefore the contamination of adjacent river and water reservoir. Soils in the shooting range were severely contaminated with Pb, as indicated by the values of enrichment and contamination factor. The concentration of Pb in these soils ranged from 791 mg kg-1 to 7265 mg kg-1, being several dozens or even hundreds of times higher compared with control background samples. A temporary stream being in close proximity was also polluted, though to a much lesser extent. The degree of Pb contamination was negatively correlated with the distance from the shooting range. To this effect, the degree of contamination of the river and the water reservoir being in the vicinity of the shooting range was negligible, as sediments and water samples preserved similar Pb concentrations with control samples. However, cultivated (olives) and wild native plant species grown in the area of the shooting range were found to uptake and accumulate high concentrations of Pb in their tissues (even 50 times higher compared with control samples). The severe contamination of soils, sediments and vegetation in the studied shooting range can provoke very high ecological risks. Overall, results suggest that management measures should be undertaken within the boundaries of the studied shooting range.

Investigating white matter structure in social anxiety disorder using fixel-based analysis.

Social anxiety disorder (SAD) is one of the most common mental health disorders in youth, defined by a persistent and intense fear of negative evaluation by others. Recent research has examined its neurological underpinnings, including structural connectivity changes in the brain. This has been examined through measurement of the white matter (WM) structure of fibre pathways. Previous studies have shown inconsistent results. This study attempts to resolve these inconsistencies by utilising a recently proposed, advanced method for diffusion MRI analysis, known as fixel based analysis (FBA). This technique enables examination of WM macro- and micro-structure with measures of fibre density (FD), fibre bundle cross-section (FC) and fibre density-cross-section (FDC). This study evidenced increased FDC in a region of the right superior longitudinal fasciculus (SLF) from a whole brain FBA, along with increased FC and FDC from an analysis restricted to a-priori tracts of interest, in regions of the right inferior longitudinal fasciculus (R-ILF). The average FDC of the left uncinate fasciculus (L-UF) was also increased. To examine the relationship between WM structure and severity of symptoms, these FBA metrics were correlated with Leibowitz Social Anxiety Scale (LSAS) scores. From the tract-restricted analysis an inverse correlation between FC and LSAS scores was found in the R-ILF. The average FC of the R-ILF was also inversely correlated with symptom severity. By utilising a more sensitive and fibre-specific method of analysis than previous studies, these findings highlight innovative outcomes relating to white matter in numerous fibre tracts.

Perceptions of social and work functioning are related to social anxiety and executive function in autistic adults.

LAY ABSTRACT: Many autistic adults have trouble in social situations and at work. Researchers do not know exactly why autistic people might find it difficult in these environments, and no studies to date have looked the way anxiety or other cognitive processes might affect autistic peoples' ability to socialise and succeed in getting and keeping jobs. Anxiety (how much you worry) and difficulty with getting stuff done or switching attention (known as executive function) can be concerns for autistic people and may contribute to social and work difficulties. This study looked at the relationships between the way autistic people perceived their anxiety and executive functioning and their ability to socialise and work. Sixty-two autistic participants completed questionnaires related to their ability to socialise and work, their social anxiety and their executive function. We found that participants who thought that they had poorer ability to work also found themselves to have more difficulties with executive function and they were more socially anxious. Our results showed that how autistic participants perceived their social anxiety and executive function were important in their perception of their social skills and work ability. This study supports the idea that anxiety and executive function could be targeted in interventions to support autistic people and their social and work outcomes.

Distress, quality of life and disability in treatment-seeking young adults with social anxiety disorder.

AIM: This study aimed to: (a) examine whether treatment-seeking young adults with social anxiety disorder (SAD) demonstrate similar degrees of distress, quality of life (QoL) and disability to those with other mental disorders; and (b) investigate the impact of comorbidity, specific comorbid conditions and antidepressants use on distress, QoL and disability in treatment-seeking young adults with SAD. METHODS: A cohort of treatment-seeking young adults (aged 16-45) diagnosed with SAD (N = 298) or other mental health disorders (N = 842; including depression, N = 349; bipolar, N = 141; psychosis, N = 173) completed self-report assessments of distress, QoL and disability. RESULTS: Young adults with SAD showed distress and disability of similar degree to those with most other mental disorders. Specifically, young adults with SAD reported significantly lower QoL than those with major depressive disorder or obsessive-compulsive disorder. Furthermore, young adults with SAD had the most difficulties in getting along with others and the second highest level of distress in comparison to other psychiatric groups. In comparison to antidepressants use, the presence of comorbidity showed a substantial negative influence on these health outcomes, particularly when presenting with comorbid depression or obsessive-compulsive disorder. CONCLUSIONS: Findings highlight significant impairments in young adults seeking treatment for SAD and the important moderating influence of comorbidity. This emphasizes the urgent need for effective management and treatment for its presentation and comorbidities in mental health services targeting young adults.

Autism spectrum disorder: An examination of sex differences in neuropsychological and self-report measures of executive and non-executive cognitive function.

LAY ABSTRACT: Research comparing females and males with a diagnosis of autism suggests that there are sex differences in some characteristics such as behaviour regulation. One area not studied in detail is whether females and males with autism perform differently in tests of cognitive ability. The results of previous research are quite mixed. One explanation may be that some research comparing females and males with autism did not include a neurotypical control group for comparison. As a result, it is not clear whether the sex differences in cognitive ability observed in people with autism are similar to differences between neurotypical males and females. To better understand whether there are unique differences between males and females with autism, it is important to also compare them with neurotypical males and females. In our research, we included a neurotypical group and compared males and females with and without a diagnosis of autism. We found that the sex differences in autism are similar to what we observe in males and females without autism. Our study showed that compared with males, females (with and without autism) do better in assessments of processing speed, cognitive flexibility, verbal learning and memory and semantic fluency. Our results suggest that although females show different cognitive performance to males, these sex differences were not specific to the group with a diagnosis of autism.

Pulse sequences for measuring exchange rates between proton species: From unlocalised NMR spectroscopy to chemical exchange saturation transfer imaging.

Within the field of NMR spectroscopy, the study of chemical exchange processes through saturation transfer techniques has a long history. In the context of MRI, chemical exchange techniques have been adapted to increase the sensitivity of imaging to small fractions of exchangeable protons, including the labile protons of amines, amides and hydroxyls. The MR contrast is generated by frequency-selective irradiation of the labile protons, which results in a reduction of the water signal associated with transfer of the labile protons' saturated magnetization to the protons of the surrounding free water. The signal intensity depends on the rate of chemical exchange and the concentration of labile protons as well as on the properties of the irradiation field. This methodology is referred to as CEST (chemical exchange saturation transfer) imaging. Applications of CEST include imaging of molecules with short transverse relaxation times and mapping of physiological parameters such as pH, temperature, buffer concentration and chemical composition due to the dependency of this chemical exchange effect on all these parameters. This article aims to describe these effects both theoretically and experimentally. In depth analysis and mathematical modelling are provided for all pulse sequences designed to date to measure the chemical exchange rate. Importantly, it has become clear that the background signal from semi-solid protons and the presence of the Nuclear Overhauser Effect (NOE), either through direct dipole-dipole mechanisms or through exchange-relayed signals, complicates the analysis of CEST effects. Therefore, advanced methods to suppress these confounding factors have been developed, and these are also reviewed. Finally, the experimental work conducted both in vitro and in vivo is discussed and the progress of CEST imaging towards clinical practice is presented.

Intraindividual variability in verbal fluency performance is moderated by and predictive of mild cognitive impairments.

OBJECTIVE: The current study was designed to achieve 2 primary objectives: (a) determine the moderating effect of mild cognitive impairments (MCI) on intraindividual variability in semantic and letter fluency performance taking into account longitudinal annual assessments; and (b) establish predictive utility for intraindividual variability in semantic and letter fluency performance as a risk factor of incident MCI. METHODS: Participants were community-residing older adults (n = 514; M age = 75.89 ± 6.45; 55.1% female). Sixty participants were diagnosed with MCI at baseline and 50 developed incident MCI during the follow-up. We operationalized intraindividual variability as word generation slopes derived from 3 consecutive time intervals during the standard 1-min administration of both letter and semantic fluency tasks (i.e., 0-20 s, 21-40 s, and 41-60 s). RESULTS: Linear mixed effects models revealed significant within task slope effects for semantic (estimate = -8.350; p < .0001; 95% confidence interval [CI] = -8.604, -8.095) and letter (estimate = -5.068; p < .0001; 95% CI [-5.268, -4.869]) fluency indicating that word generation declined over the course of both tasks. The two-way interactions of MCI × Slope were significant for semantic (estimate = 1.34; p = .001; 95% CI [0.551, 2.126]) and letter (estimate = 0.733; p = .020; 95% CI [0.116, 1.350]) fluency indicating attenuated slopes among MCI participants compared to controls taking into account repeated annual assessments. Cox proportional-hazards models revealed that attenuated word generation slope, at baseline, in semantic (hazard ratio [HR] = 2.063; p = .015; 95% = 1.149 to 3.702) but not letter (HR = 0.704; p = .243; 95% CI [0.391, 1.269]) fluency was associated with increased risk of incident MCI. CONCLUSION: Intraindividual variability in verbal fluency performance has clinical and predictive utility; it can be easily incorporated into testing batteries in clinical and research settings. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

The role of APT imaging in gliomas grading: A systematic review and meta-analysis.

PURPOSE: Gliomas are diagnosed and staged by conventional MRI. Although non-conventional sequences such as perfusion-weighted MRI may differentiate low-grade from high-grade gliomas, they are not reliable enough yet. The latter is of paramount importance for patient management. In this regard, we aim to evaluate the role of Amide Proton Transfer (APT) imaging in grading gliomas as a non-invasive tool to provide reliable differentiation across tumour grades. METHODS: A systematic search of PubMed, Medline and Embase was conducted to identify relevant publications between 01/01/2008 and 15/09/2020. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to assess studies' quality. A random-effects model standardized mean difference meta-analysis was performed to assess APT's ability to differentiate low-grade gliomas (LGGs) from high-grade gliomas (HGGs), WHO 2-4 grades, wild-type from mutated isocitrate dehydrogenase (IDH) gliomas, methylated from unmethylated O6-methylguanine-DNA methyltransferase (MGMT) gliomas. Area under the curve (AUC) of the Receiver Operating Characteristic (ROC) meta-analysis was employed to assess the diagnostic performance of APT. RESULTS: 23 manuscripts met the inclusion criteria and reported the use of APT to differentiate glioma grades with histopathology as reference standard. APT-weighted signal intensity can differentiate LGGs from HGGs with an estimated size effect of (-1.61 standard deviations (SDs), p < 0.0001), grade 2 from grade 3 (-1.83 SDs, p = 0.005), grade 2 from grade 4 (-2.34 SDs, p < 0.0001) and IDH wild-type from IDH mutated (0.94 SDs, p = 0.003) gliomas. The combined AUC of 0.84 highlights the good diagnostic performance of APT-weighted imaging in differentiating LGGs from HGGs. CONCLUSIONS: APT imaging is an exciting prospect in differentiating LGGs from HGGs and with potential to predict the histopathological grade. However, more studies are required to optimize and improve its reliability.

Insulin-like Growth Factor-1 and IGF Binding Proteins Predict All-Cause Mortality and Morbidity in Older Adults.

While the growth hormone/insulin-like growth factor-1 (GH/IGF-1) pathway plays essential roles in growth and development, diminished signaling via this pathway in model organisms extends lifespan and health-span. In humans, circulating IGF-1 and IGF-binding proteins 3 and 1 (IGFBP-3 and 1), surrogate measures of GH/IGF-1 system activity, have not been consistently associated with morbidity and mortality. In a prospective cohort of independently-living older adults (n = 840, mean age 76.1 ± 6.8 years, 54.5% female, median follow-up 6.9 years), we evaluated the age- and sex-adjusted hazards for all-cause mortality and incident age-related diseases, including cardiovascular disease, diabetes, cancer, and multiple-domain cognitive impairment (MDCI), as predicted by baseline total serum IGF-1, IGF-1/IGFBP-3 molar ratio, IGFBP-3, and IGFBP-1 levels. All-cause mortality was positively associated with IGF-1/IGFBP-3 molar ratio (HR 1.28, 95% CI 1.05-1.57) and negatively with IGFBP-3 (HR 0.82, 95% CI 0.680-0.998). High serum IGF-1 predicted greater risk for MDCI (HR 1.56, 95% CI 1.08-2.26) and composite incident morbidity (HR 1.242, 95% CI 1.004-1.538), whereas high IGFBP-1 predicted lower risk for diabetes (HR 0.50, 95% CI 0.29-0.88). In conclusion, higher IGF-1 levels and bioavailability predicted mortality and morbidity risk, supporting the hypothesis that diminished GH/IGF-1 signaling may contribute to human longevity and health-span.