The increase in medical admissions with anorexia nervosa during the COVID-19 pandemic in Western Australia.

OBJECTIVE: A comparative study to describe the increase in medical admissions of children and adolescents with anorexia nervosa (AN) in Western Australia in 2019 (pre-pandemic) and 2020 (peri-pandemic). METHOD: Patient demographics, physiological parameters, length of stay, time to assessment by the Eating Disorder Service (EDS), and commencement of specialist eating disorder (ED) outpatient treatment was collected for adolescents admitted with AN between 1st January 2019 and 31st December 2020. RESULTS: The number of admissions doubled from 126 in 2019 to 268 in 2020. The number of children admitted increased by 52%. The median length of hospital stay was shorter in 2020 (12 vs. 17 days; p < .001), but the 28-day readmission rate was greater (39.9% vs. 22.2%; p < .001). At the time of hospital discharge in 2020, only 60% of patients were able to step-down into specialist ED outpatient treatment, compared to 93% in 2019. The mean number of admissions per child before completing EDS assessment increased significantly in 2020 (2.75 vs. 0, p < .001). DISCUSSION: Shorter inpatient stays and delays in the commencement of specialist ED outpatient treatment may have contributed to the increased readmission rate seen in 2020. PUBLIC SIGNIFICANCE: This research is important as it explores the reasons for increased medical presentations and admissions of youth with AN during the COVID-19 pandemic in Western Australia. We hope that our lessons learned may be helpful to others trying to balance similar clinical workloads.

Influence of Research Involvement on the Interpretation and Implementation of a Research Competency in Dietetic Internship Programs.

BACKGROUND: Experiential learning theory was utilized as the overarching framework for this study because the research experiences of dietetic internship (DI) directors likely influences the way they manage the DI research curriculum. The literature suggests that dietitians and dietetic educators lack research knowledge and skills, resulting in a research-competency gap. The purpose of this study was to examine the relationship of the research involvement of DI directors and their interpretation and implementation of a research competency within their programs. METHODS: This study utilized a cross-sectional, survey design, which consisted of DI directors who managed ACEND accredited DI programs (n=96). RESULTS: The data indicated that the research involvement of DI directors influences both their interpretation and implementation of the research competency. Discriminant analysis revealed that level of research involvement differentiated significantly among interpretation and implementation of the research competency. CONCLUSIONS: The results of this study showed DI directors who scored higher on the research involvement continuum had a more complete interpretation and implementation of the research competency, which reinforces the importance of experiential learning. These findings could be used by DI directors and other dietetic educators to inform curricular decisions that bridge the research-competency gap between curriculum and practice within dietetics.

Examining mechanisms of brain control of bladder function with resting state functional connectivity MRI.

AIMS: This aim of this study is to identify the brain mechanisms involved in bladder control. METHODS: We used fMRI to identify brain regions that are activated during bladder filling. We then used resting state connectivity fMRI (rs-fcMRI) to assess functional connectivity of regions identified by fMRI with the rest of the brain as the bladder is filled to capacity. RESULTS: Female participants (n = 20) were between ages 40 and 64 with no significant history of symptomatic urinary incontinence. Main effect of time (MET) fMRI analysis resulted in 20 regions of interest (ROIs) that have significant change in BOLD signal (z = 3.25, P <0.05) over the course of subtle bladder filling and emptying regardless of full versus empty bladder state. Bladder-state by time (BST) fMRI analysis resulted in three ROIs that have significant change in BOLD signal (z = 3.25, P <0.05) over the course of bladder runs comparing full versus empty bladder state. Rs-fcMRI fixed effects analysis identified significant changes in connectivity between full and empty bladder states in seven brain regions (z = 4.0) using the three BST ROIs and sixteen brain regions (z = 7) using the twenty MET ROIs. Regions identified include medial frontal gyrus, posterior cingulate (PCC), inferiolateral temporal and post-central gyrus, amygdale, the caudate, inferior parietal lobe as well as anterior and middle cingulate gyrus. CONCLUSIONS: There is significant and vast changes in the brain's functional connectivity when bladder is filled suggesting that the central process responsible for the increased control during the full bladder state appears to largely rely on the how distributed brain systems are functionally integrated.

Comparative in vitro bioactivities of tea extracts from six species of Ardisia and their effect on growth inhibition of HepG2 cells.

AIM OF THE STUDY: Ardisia species, notably A. compressa, are used in some regions of the world as food or in traditional medicine for prevention and treatment of certain health conditions including liver disease. We investigated the chemical composition and relative anticancer potential of six Ardisia species [A. japonica (AJ), A. escallonioides (AES), A. mamillata (AM), A. compressa (AC), A. crenata (ACR), and A. elliptica (AE)]. MATERIALS AND METHODS: Antioxidant capacity, DNA human topoisomerase II catalytic inhibition, and cytotoxicity on human liver cancer cells (HepG2) were determined in vitro in tea extracts of the 6 Ardisia species evaluated. Selected pure phenolic compounds present in Ardisia species were also evaluated. RESULTS: AC showed the highest topoisomerase II catalytic inhibition (IC(50)=12 microg/ml) and cytotoxicity (IC(50)=117 microg/ml) against HepG2 cells, followed by ACR and AJ. Total polyphenols ranged from 21 to 72 mg equivalents of gallic acid (GA)/g solid extract (SE). LC-MS analysis revealed the presence of GA, quercetin derivatives, ardisenone, ardisiaquinone, ardisianone, bergenin, norbergenin, and embelin. However, neither total polyphenol concentration nor antioxidant capacity correlated with anticancer capacity. Significant HepG2 cytotoxicity was also achieved by bergenin (IC(50)=18 microM) and embelin (IC(50)=120 microM). AC, bergenin, embelin, and quercetin showed a tendency to accumulate cells in the G1 phase and reduced G2/M leading to apoptosis. CONCLUSIONS: Although the mechanism is not entirely clear, AC, ACR, and AJ are the Ardisia species with the greatest anticancer potential against liver cancer cells in vitro and deserve further investigation.

Circle of Willis atherosclerosis: association with Alzheimer's disease, neuritic plaques and neurofibrillary tangles.

The role of intracranial atherosclerosis in Alzheimer's disease (AD) has been a subject of debate since the first decade of the last century. The initial "vascular hypothesis" of AD was rejected after a series of mid-twentieth century gross anatomical postmortem studies that showed an inconstant relationship between intracranial atherosclerosis and senile dementia. These early studies did not utilize statistical methods, however, and the investigators did not appear to consider the possibility that intracranial atherosclerosis might have a probabilistic, rather than an absolute, effect on AD risk. Recent studies by three independent groups have found a significant statistical association between postmortem measures of circle of Willis atherosclerosis and AD. The present study was undertaken to further address the validity of this association in a large autopsy series, including cases diagnosed neuropathologically with vascular dementia (VaD) and non-AD dementias. Postmortem gross anatomical grading of circle of Willis atherosclerosis was performed in 397 subjects classified by neuropathological diagnosis, including 92 non-demented elderly controls, 215 with AD, 30 with VaD and 60 with non-AD dementias. Circle of Willis atherosclerosis was more severe in subjects with AD and VaD than in control subjects, while it was equivalent between control subjects and subjects with non-AD dementias. Increasing atherosclerotic grade increased the odds ratios (OR) for the diagnoses of both AD and VaD and also increased the ORs for both increased neuritic plaque density and higher Braak neurofibrillary tangle stage. The significance of these associations was retained after consideration of the effects of age, gender and the apolipoprotein E-epsilon4 allele. The results suggest that the statistical association between intracranial atherosclerosis and AD is not an artifact of diagnostic misclassification or of unequal distribution of the apolipoprotein E-epsilon4 allele.

Altered APP processing in PDAPP (Val717 --> Phe) transgenic mice yields extended-length Abeta peptides.

Central to the pathology of Alzheimer's disease (AD) is the profuse accumulation of amyloid-beta (Abeta) peptides in the brain of affected individuals, and several amyloid precursor protein (APP) transgenic (Tg) mice models have been created to mimic Abeta deposition. Among these, the PDAPP Tg mice carrying the familial AD APP 717 Val --> Phe mutation have been widely used to test potential AD therapeutic interventions including active and passive anti-Abeta immunizations. The structure and biochemistry of the PDAPP Tg mice Abeta-related peptides were investigated using acid and detergent lysis of brain tissue, ultracentrifugation, FPLC, HPLC, enzymatic and chemical cleavage of peptides, Western blot, immunoprecipitation, and MALDI-TOF and SELDI-TOF mass spectrometry. Our experiments reveal that PDAPP mice produce a variety of C-terminally elongated Abeta peptides in addition to Abeta n-40 and Abeta n-42, as well as N-terminally truncated peptides, suggesting anomalous proteolysis of both APP and Abeta. Important alterations in the overall APP degradation also occur in this model, resulting in a striking comparative lack of CT83 and CT99 fragments, which may be inherent to the strain of mice, a generalized gamma-secretase failure, or the ultimate manifestation of the overwhelming amount of expressed human transgene; these alterations are not observed in other strains of APP Tg mice or in sporadic AD. Understanding at the molecular level the nature of these important animal models will permit a better understanding of therapeutic interventions directed to prevent, delay, or reverse the ravages of sporadic AD.

Substantia nigra Marinesco bodies are associated with decreased striatal expression of dopaminergic markers.

Marinesco bodies are nuclear inclusions found in pigmented neurons of the substantia nigra and locus ceruleus of humans and monkeys. It has long been known that the frequency of these inclusions increases with advancing age, but no pathologic associations have ever been established. We quantified Marinesco body frequency in human autopsy subjects, classified as young normal controls, elderly controls, dementia with Lewy bodies (DLB), Alzheimer disease (AD), and Parkinson disease (PD). Elderly controls, AD cases, and DLB cases had significantly increased Marinesco body frequencies relative to young controls and DLB cases had significantly increased frequencies relative to elderly controls, while PD cases did not differ from young controls; cases with AD did not differ from elderly controls. Lewy body-containing neurons had significantly higher Marinesco body frequencies than non-Lewy body-containing neurons. Marinesco body frequency in elderly control cases correlated significantly, in inverse fashion, with striatal concentrations of the dopaminergic neuron markers dopamine transporter and tyrosine hydroxylase. These statistical associations suggest that Marinesco bodies constitute or mark a pathologic process that may be related to, or contribute to, age-related motor dysfunction and/or Lewy body disorders. Further studies are needed to ascertain the molecular basis of Marinesco body formation; preliminary studies indicate that proteasome dysfunction can lead to similar abnormalities in cultured cells.

Thiorphan-induced neprilysin inhibition raises amyloid beta levels in rabbit cortex and cerebrospinal fluid.

Studies on the pathogenesis of Alzheimer's disease (AD) suggest overproduction of amyloid beta (Abeta) may not be the only pathogenic route to AD. Decreased degradation of Abeta is another possible disease mechanism. Neprilysin is a neutral endopeptidase that has been proposed to be the major enzyme responsible for Abeta degradation. Studies have reported correlations between Abeta deposition and neprilysin activity in the human brain. This study shows that intracerebroventricular infusion of thiorphan, a neprilysin inhibitor, raises cortical and cerebrospinal fluid (CSF) Abeta concentrations in rabbits. Rabbits treated with thiorphan for 5 days had levels of CSF and cortical Abeta40 that were 147 and 142% of the control group, respectively. Results for Abeta42 showed a similar trend. The results indicate that age-related decreases of neprilysin could lead to increased brain concentrations of Abeta, plaque formation, and AD.

Hippocampal sclerosis dementia with tauopathy.

In some elderly individuals with dementia, hippocampal sclerosis (HS) is the only remarkable autopsy finding. The cause of HS in this setting is puzzling, since known causes of HS such as seizures or global hypoxic-ischemic episodes are rarely present. We here describe a series of HS cases that have a widespread neuronal and/or glial tauopathy. Of 14 consecutive cases of HS, 12 had been clinically diagnosed with dementia and/or Alzheimer's disease (AD) while 2 were non-demented; 7 cases had also been clinically diagnosed with parkinsonism. In addition to HS, 6 cases also met pathologic diagnostic criteria for AD. Gallyas silver staining and immunohistochemistry with the AT8 antibody revealed a glial and/or neuronal tauopathy in 12 of 14 cases, with frequent positive neurons and/or glial cells in the neocortex, basal ganglia, thalamus and/or limbic regions; in addition, 8 of the 14 cases had argyrophilic grains. Screening for known tau mutations was negative in all cases. Western blots of sarkosyl-insoluble tau protein showed a mixture of 3- and 4-repeat forms. The results suggest that most cases of HS dementia are sporadic multisystem tauopathies; we suggest the term "hippocampal sclerosis dementia with tauopathy" (HSDT) for these.