Assaying Lysosomal Enzyme Activity in Dictyostelium discoideum.

Lysosomes are membrane-enclosed organelles that digest intracellular material. They contain more than 50 different enzymes that can degrade a variety of macromolecules including nucleic acids, proteins, polysaccharides, and lipids. In addition to functioning within lysosomes, lysosomal enzymes are also secreted. Alterations in the levels and activities of lysosomal enzymes dysregulates lysosomes, which can lead to the intralysosomal accumulation of biological material and the development of lysosomal storage diseases (LSDs) in humans. Dictyostelium discoideum has a long history of being used to study the trafficking and functions of lysosomal enzymes. More recently, it has been used as a model system to study several LSDs. In this chapter, we outline the methods for assessing the activity of several lysosomal enzymes in D. discoideum (α-galactosidase, ß-galactosidase, α-glucosidase, ß-glucosidase, ß-N-acetylglucosaminidase, α-mannosidase, cathepsin B, cathepsin D, cathepsin F, palmitoyl protein thioesterase 1, and tripeptidyl peptidase 1).

Selective Btk inhibition by PRN1008/PRN473 blocks human CLEC-2 & PRN473 reduces venous thrombosis formation in mice.

Platelet CLEC-2 is a hemITAM-containing receptor which has a critical role in venous thrombosis, but minimal involvement in haemostasis. CLEC-2 can be blocked by Btk inhibitors. Treatment with ibrutinib is associated with increased bleeding due to off-target inhibition of Src family kinases (SFKs). Patients with X-linked agammaglobulinemia (XLA) who lack Btk however do not bleed, suggesting selective Btk inhibition is a viable antithrombotic strategy. We assessed the effects of selective Btk inhibitors PRN1008 (rilzabrutinib) and PRN473 on platelet signalling and function mediated by CLEC-2 and GPVI. We used healthy donor and XLA platelets to determine off-target inhibitor effects. Inferior vena cava (IVC) stenosis and Salmonella infection mouse models were used to assess antithrombotic effects of PRN473 in vivo. PRN1008 and PRN473 potently inhibited CLEC-2-mediated platelet activation to rhodocytin. No off-target inhibition of SFKs was seen. PRN1008 treatment of Btk-deficient platelets resulted in minor additional inhibition of aggregation and tyrosine phosphorylation, likely reflecting inhibition of Tec. No effect on GPCR-mediated platelet function was observed. PRN473 significantly reduced the number of thrombi in podoplanin positive vessels following Salmonella infection and the presence of IVC thrombosis following vein stenosis. The potent inhibition of human platelet CLEC-2, and reduced thrombosis in in vivo models, together with the lack of off-target SFK inhibition and absence of bleeding reported in rilzabrutinib treated immune thrombocytopenia patients, suggest Btk inhibition as a promising antithrombotic strategy.

Efficacy and acceptability of interventions to reduce antipsychotic polypharmacy: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Antipsychotic polypharmacy (APP) is frequent but evidence-based guidelines on reducing APP to antipsychotic monotherapy (APM) are sparse. We aimed to systematically review clinical interventions randomizing patients to reducing APP to APM versus continuing APP. METHODS: Systematic literature review searching Medline and Embase (latest search January 10, 2024) for randomized clinical trials (RCTs) studying interventions comparing individuals randomized to reduction of APP to APM with individuals continuing on APP. Two independent reviewers performed the literature screening, data extraction, and risk of bias assessment (RoB2). We performed random effects meta-analyses on the main outcome all-cause discontinuation/"acceptability" of the treatment strategy and secondary outcomes change in psychopathology, functional level, and side effects. RESULTS: The search identified 4672 hits, whereof 8 trials (N = 1204, 6 patient-level RCTs and 2 cluster-RCTs) were included, primarily in patients with schizophrenia. All trials were associated with high risk of bias. Compared to APP continuation, reduction to APM was associated with no significant change in all-cause discontinuation (studies = 6, n = 455, RR = 1.48, 95%CI = 0.74-2.95, I2 = 78 %) or inefficacy-related discontinuation (studies = 5, n = 351, RR = 1.60, 95%CI = 0.46-5.55, I2 = 70 %). Patients randomized to APM showed a trend towards greater reduction in psychopathology (studies = 5, n = 244, SMD = -0.24, 95%CI = -0.49, 0.02, I2 = 0 %) but no difference in functional level nor side effects. The cluster-RCTs found that interventions at the departmental level can result in lower rates of APP. CONCLUSION: Although switching patients from APP to APM can be a viable approach, too few RCTs exist on this important topic. Clinicians need to evaluate potential benefits and risks of APP and APM on an individual basis. PROSPERO REGISTRATION: CRD42022329955.

Capsid virus-like particle display improves recombinant influenza neuraminidase antigen stability and immunogenicity in mice.

Supplementing influenza vaccines with additional protective antigens such as neuraminidase (NA) is a promising strategy for increasing the breadth of the immune response. Here, we improved the immunogenicity and stability of secreted recombinant NA (rNA) tetramers by covalently conjugating them onto the surface of AP205 capsid virus-like particles (cVLPs) using a Tag/Catcher ligation system. cVLP display increased the induction of IgG2a subclass anti-NA antibodies, which exhibited cross-reactivity with an antigenically distant homologous NA. It also reduced the single dose rNA amounts needed for protection against viral challenge in mice, demonstrating a dose-sparing effect. Moreover, effective cVLP-display was achieved across different NA subtypes, even when the conjugation was performed shortly before administration. Notably, the rNA-cVLP immunogenicity was retained upon mixing or co-administering with commercial vaccines. These results highlight the potential of this approach for bolstering the protective immune responses elicited by influenza vaccines.

Anthrax Vaccination, Gulf War Illness, and Human Leukocyte Antigen (HLA).

We report on a highly significant, positive association between anthrax vaccination and occurrence of Gulf War Illness (GWI) in 111 Gulf War veterans (42 with GWI and 69 controls). GWI was diagnosed in 47.1% of vaccinated veterans but only in 17.2% of non-vaccinated veterans (Pearson χ2 = 7.08, p = 0.008; odds ratio = 3.947; relative risk = 2.617), with 1.6x higher GWI symptom severity in vaccinated veterans (p = 0.007, F-test in analysis of covariance). Next, we tested the hypothesis that the susceptibility to GWI following anthrax vaccination could be due to inability to make antibodies against the anthrax protective antigen (PA), the key protein contained in the vaccine. Since the first step in initiating antibody production would be the binding of PA peptide fragments (typically 15-amino acid long [15-mer]) to peptide-binding motifs of human leukocyte antigen (HLA) Class II molecules, we assessed the binding-motif affinities of such HLA specific molecules to all linear 15-mer peptide fragments of the anthrax PA. We identified a total of 58 HLA Class II alleles carried by the veterans in our sample and found that, of those, 18 (31%) were present in the vaccinated group that did not develop GWI but were absent from the vaccinated group who developed GWI. Remarkably, in silico analyses revealed very high binding affinities of peptide-binding motifs of those 18 HLA alleles with fragments of anthrax vaccine PA, leading to the successful production of anti-PA antibodies. Conversely, the absence of these protective HLA alleles points to a reduced ability to develop antibodies against PA, thus resulting in harmful PA persistence and development of GWI.

Nontarget and suspect screening reveals the presence of multiple plastic-related compounds in polar bear, killer whale, narwhal and long-finned pilot whale blubber from East Greenland.

The monitoring of legacy contaminants in sentinel northern marine mammals has revealed some of the highest concentrations globally. However, investigations into the presence of chemicals of emerging Arctic concern (CEACs) and other lesser-known chemicals are rarely conducted, if at all. Here, we used a nontarget/suspect approach to screen for thousands of different chemicals, including many CEACs and plastic-related compounds (PRCs) in blubber/adipose from killer whales (Orcinus orca), narwhals (Monodon monoceros), long-finned pilot whales (Globicephala melas), and polar bears (Ursus maritimus) in East Greenland. 138 compounds were tentatively identified mostly as PRCs, and four were confirmed using authentic standards: di(2-ethylhexyl) phthalate (DEHP), diethyl phthalate (DEP), di(2-propylheptyl) phthalate (DPHP), and one antioxidant (Irganox 1010). Three other PRCs, a nonylphenol isomer, 2,6-di-tert-butylphenol, and dioctyl sebacate, exhibited fragmentation patterns matching those in library databases. While phthalates were only above detection limits in some polar bear and narwhal, Irganox 1010, nonylphenol, and 2,6-di-tert-butylphenol were detected in >50% of all samples. This study represents the first application of a nontarget/suspect screening approach in Arctic cetaceans, leading to the identification of multiple PRCs in their blubber. Further nontarget analyses are warranted to comprehensively characterize the extent of CEAC and PRC contamination within Arctic marine food webs.

Remote feedback in endovascular simulation training: a mixed-methods study.

BACKGROUND: There is an increasing need to increase simulation-based learning opportunities for vascular surgery residents in endovascular skills training. This study aims to explore the effectiveness of remote expert instructional feedback of endovascular simulation-based education, as a means of increasing training opportunities in this area for vascular surgery residents. METHODS: A mixed-methods study design was adopted. Twelve vascular surgery residents from Ireland were tasked with completing two endovascular renal artery procedures: one with in-person expert feedback and the other with remote instruction. Participants ranged in experience levels from second year to final year of residency. Following the training activities, interviews and a questionnaire were employed to gather information on the usefulness of remote feedback. RESULTS: There was no significant difference reported by participants using a post-event validated questionnaire between remote and in-person feedback. During the interviews, participants expressed mixed feelings about the presence of the educator while practicing, but they eventually saw no limiting factors to their practice when the trainer provided remote feedback. When receiving performance feedback remotely, clear communication and a shared knowledge of the task development are critical to success. CONCLUSIONS: We believe these findings can inform the design and development of remote learning and assessment of endovascular skills training and ultimately provide increased opportunities for more skills practice for vascular surgical residents.

Loading and thermal behaviour of ZIF-8 metal-organic framework-inorganic glass composites.

Here we describe the synthesis of a compositional series of metal-organic framework crystalline-inorganic glass composites (MOF-CIGCs) containing ZIF-8 and an inorganic phosphate glass, 20Na2O-10NaCl-70P2O5, to expand the library of host matrices for metal-organic frameworks. By careful selection of the inorganic glass component, a relatively high loading of ZIF-8 (70 wt%) was achieved, which is the active component of the composite. A Zn⋯O-P interfacial bond, previously identified in similar composites/hybrid blends, was suggested by analysis of the total scattering pair distribution function data. Additionally, CO2 and N2 sorption and variable-temperature PXRD experiments were performed to assess the composites' properties.

End of Life Outcomes Following Comfort Care Orders: A Single Center Experience.

Background: Few studies have explored the outcomes of patients placed on comfort care with respect to hospice disposition. The objective of this study was to perform a retrospective analysis of patients who transitioned to comfort care. Methods: We conducted a retrospective study of patients placed on the comfort care order set between July 1st, 2021, until June 30th, 2022. Each individual patient chart was then analyzed to collect multiple clinical variables. IRB approval was obtained as per institutional guidelines. Results: 541 patients were included in the analysis. An average of 1.5 patients were placed on comfort care a day. 424 (78.37%) patients died while in the hospital. The median time on comfort care was 1 day. For subspecialty and hospital medicine patients the median time was 2 days. 40% of non-ICU patients were discharged with hospice services. 60% of patients were in the intensive care unit (ICU) and spent a median of 2.33 hours on comfort care. 19% of these patients were on comfort care for over 12 hours. 94% of the patients placed on comfort care in the ICU died in the hospital as compared to 53% of subspecialty and 59% of hospital medicine patients. Conclusions: The majority of patients placed on comfort care died during their hospitalization demonstrating a real need for comprehensive end of life care and immediate hospice services. For those discharged with hospice services, they spent an excessive amount of time in the hospital waiting for services to be arranged.

Comparative analysis of cholera serum vibriocidal antibodies from Convalescent and vaccinated adults in Zambia.

Cholera is responsible for 1.3 to 4.0 million cholera cases globally and poses a significant threat, with Zambia reporting 17,169 cases as of 4th February 2024. Recognizing the crucial link between natural cholera infections and vaccine protection, this study aimed to assess immune responses post cholera infection and vaccination. This was a comparative study consisting of 50 participants enrolled during a cholera outbreak in Zambia's Eastern Province and an additional 56 participants who received oral cholera vaccinations in Zambia's Central Province. Vibriocidal antibodies were plotted as geometric mean titres in the naturally infected and vaccinated individuals. A significant difference (p < 0.047) emerged when comparing naturally infected to fully vaccinated individuals (2 doses) on day 28 against V. cholerae Ogawa. Those who received two doses of the oral cholera vaccine had higher antibody titres than those who were naturally infected. Notably, the lowest titres occurred between 0-9 days post onset, contrasting with peak responses at 10-19 days. This study addresses a critical knowledge gap in understanding cholera immunity dynamics, emphasizing the potential superiority of vaccination-induced immune responses. We recommend post infection vaccination after 40 days for sustained immunity and prolonged protection, especially in cholera hotspots.

The late positive event-related potential component is time locked to the decision in recognition memory tasks.

Two event-related potential (ERP) components are commonly observed in recognition memory tasks: the Frontal Negativity (FN400) and the Late Positive Component (LPC). These components are widely interpreted as neural correlates of familiarity and recollection, respectively. However, the interpretation of LPC effects is complicated by inconsistent results regarding the timing of ERP amplitude differences. There are also mixed findings regarding how LPC amplitudes covary with decision confidence. Critically, LPC effects have almost always been measured using fixed time windows relative to memory probe stimulus onset, yet it has not been determined whether LPC effects are time locked to the stimulus or the recognition memory decision. To investigate this, we analysed a large (n = 132) existing dataset recorded during recognition memory tasks with old/new decisions followed by post-decisional confidence ratings. We used ERP deconvolution to disentangle contributions to LPC effects (defined as differences between hits and correct rejections) that were time locked to either the stimulus or the vocal old/new response. We identified a left-lateralised parietal LPC effect that was time locked to the vocal response rather than probe stimulus onset. We also isolated a response-locked, midline parietal ERP correlate of confidence that influenced measures of LPC amplitudes at left parietal electrodes. Our findings demonstrate that, contrary to widespread assumptions, the LPC effect is time locked to the recognition memory decision and is best measured using response-locked ERPs. By extension, differences in response time distributions across conditions of interest may lead to substantial measurement biases when analysing stimulus-locked ERPs. Our findings highlight important confounding factors that further complicate the interpretation of existing stimulus-locked LPC effects as neural correlates of recollection. We recommend that future studies adopt our analytic approach to better isolate LPC effects and their sensitivity to manipulations in recognition memory tasks.

A scoping review on bovine tuberculosis highlights the need for novel data streams and analytical approaches to curb zoonotic diseases.

Zoonotic diseases represent a significant societal challenge in terms of their health and economic impacts. One Health approaches to managing zoonotic diseases are becoming more prevalent, but require novel thinking, tools and cross-disciplinary collaboration. Bovine tuberculosis (bTB) is one example of a costly One Health challenge with a complex epidemiology involving humans, domestic animals, wildlife and environmental factors, which require sophisticated collaborative approaches. We undertook a scoping review of multi-host bTB epidemiology to identify trends in species publication focus, methodologies, and One Health approaches. We aimed to identify knowledge gaps where novel research could provide insights to inform control policy, for bTB and other zoonoses. The review included 532 articles. We found different levels of research attention across episystems, with a significant proportion of the literature focusing on the badger-cattle-TB episystem, with far less attention given to tropical multi-host episystems. We found a limited number of studies focusing on management solutions and their efficacy, with very few studies looking at modelling exit strategies. Only a small number of studies looked at the effect of human disturbances on the spread of bTB involving wildlife hosts. Most of the studies we reviewed focused on the effect of badger vaccination and culling on bTB dynamics with few looking at how roads, human perturbations and habitat change may affect wildlife movement and disease spread. Finally, we observed a lack of studies considering the effect of weather variables on bTB spread, which is particularly relevant when studying zoonoses under climate change scenarios. Significant technological and methodological advances have been applied to bTB episystems, providing explicit insights into its spread and maintenance across populations. We identified a prominent bias towards certain species and locations. Generating more high-quality empirical data on wildlife host distribution and abundance, high-resolution individual behaviours and greater use of mathematical models and simulations are key areas for future research. Integrating data sources across disciplines, and a "virtuous cycle" of well-designed empirical data collection linked with mathematical and simulation modelling could provide additional gains for policy-makers and managers, enabling optimised bTB management with broader insights for other zoonoses.

Association between multimorbidity and cognitive decline in the elderly population of the Eastern Province, Saudi Arabia.

BACKGROUND: Cognitive decline affects the quality of life, and dementia affects independence in daily life activities. Multimorbidity in older adults is associated with a higher risk of cognitive impairment. This research aims to study the relationship between cognitive decline and multimorbidity in the elderly population in the Eastern Province, Saudi Arabia. MATERIALS AND METHODS: This cross-sectional research was conducted from July to October 2022 among adults over 60 years. All patients with two or more comorbidities were contacted for a face-to-face interview and cognitive testing to estimate cognitive function by trained family physicians using St. Louis University Mental State Examination. ANOVA and Chi-square test were used to test for statistical significance. Binary logistic regression was used to show the odds of having cognitive impairment and multimorbidity. All tests were performed at 5% level of significance. RESULTS: The study involved 343 individuals; majority (74.1%) aged 60-75 years and were males (67.9%). Hypertension, diabetes, and chronic pain were reported by 56%, 48%, and 44% participants, respectively. Thirty percent participants had 3 or more comorbidities. About 36% had mild neurocognitive disorder and 31.2% had dementia. The results showed that age, gender (female), diabetes, stroke, chronic pain, and multimorbidity were significantly associated with cognitive impairment. In our study, hypertension, coronary artery diseases, depression, and anxiety were not significantly associated with risk of cognitive decline. CONCLUSION: Our study found that multimorbidity is significantly associated with cognitive decline. Controlling comorbidities and preventing risk factors in midlife could help in delaying the progression of the disease.

Respiratory symptoms and outcomes among cigar smokers: findings from the Population Assessment of Tobacco and Health (PATH) study waves 2-5 (2014-2019).

BACKGROUND: The mechanisms by which cigarette smoking increases the risk of respiratory disease have been studied. However, less is known about risks of respiratory symptoms and outcomes associated with smoking cigars, and risks by cigar types have not been previously explored. The aim of this study was to examine associations between cigar use, including traditional cigars, cigarillos, filtered cigars, and dual cigar and cigarette use, and functionally important respiratory symptoms (FIRS), lifetime asthma diagnosis, uncontrolled asthma, and new cases of FIRS. METHODS: Data from Waves 2-5 (2014-19) of the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative longitudinal study, were analyzed in two ways. For cross-sectional analysis, the analytic sample included adults 18 and older at each wave, resulting in 44,040 observations. Separately, longitudinal analyses were assessed among adults 18 and older at Wave 2, resulting in 7,930 individuals. Both analyses excluded adults with chronic obstructive pulmonary disease (COPD) or non-asthma respiratory disease. RESULTS: Current established cigarillo smokers had higher odds of having FIRS (Adjusted odds ratio (AOR): 1.72; 95% CI: 1.08, 2.74) compared to never smokers of cigarillos and cigarettes, after adjusting for covariates. Current established filtered cigar smokers had higher odds of asthma diagnosis (AOR: 1.35; 95% CI: 1.10, 1.66) while current established dual smokers of filtered cigars and cigarettes had higher odds of uncontrolled asthma (AOR: 5.13; 95% CI: 1.75, 15.02) compared to never smokers of filtered cigars or cigarettes. Both current established cigar smokers and current established dual smokers of cigarettes and cigars had higher odds of new FIRS compared to never cigar or cigarette smokers (AORs: 1.62; 95% CI: 1.02, 2.60 for exclusive cigars and 2.55; 95% CI 1.57, 4.14 for dual smokers). CONCLUSIONS: This study provides evidence that cigar smokers or dual smokers of cigars and cigarettes have greater odds of FIRS, asthma, and uncontrolled asthma and that new incidence of FIRS is higher among any cigar smokers compared to never cigar or cigarette smokers. Understanding health impacts associated with cigar use provides information for supporting policy development, as well as for designing clinical interventions focused on smoking cessation for cigars.

Seroconversion and Kinetics of Vibriocidal Antibodies during the First 90 Days of Re-Vaccination with Oral Cholera Vaccine in an Endemic Population.

Despite the successful introduction of oral cholera vaccines, Zambia continues to experience multiple, sporadic, and protracted cholera outbreaks in various parts of the country. While vaccines have been useful in staying the cholera outbreaks, the ideal window for re-vaccinating individuals resident in cholera hotspot areas remains unclear. Using a prospective cohort study design, 225 individuals were enrolled and re-vaccinated with two doses of Shanchol™, regardless of previous vaccination, and followed-up for 90 days. Bloods were collected at baseline before re-vaccination, at day 14 prior to second dosing, and subsequently on days 28, 60, and 90. Vibriocidal assay was performed on samples collected at all five time points. Our results showed that anti-LPS and vibriocidal antibody titers increased at day 14 after re-vaccination and decreased gradually at 28, 60, and 90 days across all the groups. Seroconversion rates were generally comparable in all treatment arms. We therefore conclude that vibriocidal antibody titers generated in response to re-vaccination still wane quickly, irrespective of previous vaccination status. However, despite the observed decline, the levels of vibriocidal antibodies remained elevated over baseline values across all groups, an important aspect for Zambia where there is no empirical evidence as to the ideal time for re-vaccination.

Divergence in Cigarette Discontinuation Rates by Use of Electronic Nicotine Delivery Systems (ENDS): Longitudinal Findings From the United States PATH Study Waves 1-6.

INTRODUCTION: We compare real-world trends in population-level cigarette discontinuation rates among adults (ages ≥21) who smoked cigarettes, by electronic nicotine delivery systems (ENDS) use. AIMS AND METHODS: U.S nationally representative data from adults in the Population Assessment of Tobacco and Health (PATH) Study (2013/14-2021, Waves 1-6) who smoked cigarettes in the past 30 days (P30D) were analyzed (n = 13 640). The exposure was P30D ENDS use. The outcome was P30D cigarette discontinuation at biennial follow-up. Weighted trend analyses were conducted to test for differences in cigarette discontinuation trends by ENDS use. RESULTS: Between 2013/14 and 2015/16, cigarette discontinuation rates were both 16% for those who used ENDS and for those who did not; between 2018/19 and 2021, rates were ~30% for those who used ENDS and ~20% for those who did not; the time by ENDS use interaction was significant. CONCLUSIONS: The relationship between adults' ENDS use and cigarette discontinuation in the context of an expanded ENDS marketplace, new tobacco regulatory actions, and COVID-19 differs from the relationship in earlier years. IMPLICATIONS: It is important for public health decisions to be informed by research based on the contemporary ENDS marketplace and circumstances.

Do human-wildlife interactions predict offspring hiding strategies in peri-urban fallow deer?

Human activities can induce significant behavioural changes in wildlife. Often explored through extractive interactions (e.g. hunting) that can favour certain behavioural traits, the implications of non-extractive ones, such as wildlife feeding, remain understudied. Research shows that people tend to favour bolder individuals within populations despite their dynamics and consequences being unclear. Using fallow deer in a peri-urban environment, we studied whether mothers that show reduced fear of humans and consistently approach them for food adopt weaker anti-predator strategies by selecting less concealed fawning bedsites closer to human hotspots. This would provide the advantage of additional feeding opportunities in comparison with shyer mothers while keeping their fawns close. Our dataset encompassed 281 capture events of 172 fawns from 110 mothers across 4 years. Surprisingly, mothers that regularly accepted food from humans selected more concealed bedsites farther from human hotspots, giving their offspring better protection while also benefitting from additional food during lactation. Our results show behavioural adaptations by a subset of females and, for the first time, link the tendency to approach humans and strategies to protect offspring. Given previous findings that these begging females also deliver heavier fawns at birth, our research further investigates human-wildlife feeding interactions and their behavioural implications.

Design and utilisation of a novel, high-fidelity, low-cost, hybrid-tissue simulation model to facilitate training in robot-assisted partial nephrectomy.

Robot-assisted partial nephrectomy (RAPN) has rapidly evolved as the standard of care for appropriately selected renal tumours, offering key patient benefits over radical nephrectomy or open surgical approaches. Accordingly, RAPN is a key competency that urology trainees wishing to treat kidney cancer must master. Training in robotic surgery is subject to numerous challenges, and simulation has been established as valuable step in the robotic learning curve. However, simulation models are often both expensive and suboptimal in fidelity. This means that the number of practice repetitions for a trainee may limited by cost restraints, and that trainees may struggle to reconcile the skills obtained in the simulation laboratory with real-world practice in the operating room. We have developed a high-fidelity, low-cost, customizable model for RAPN simulation based on porcine tissue. The model has been utilised in teaching courses at our institution, confirming both feasibility of use and high user acceptability. We share the design of our model in this proof-of-concept report.

EEG Frequency Correlates with α2-Receptor Density in Parkinson's Disease.

INTRODUCTION: Increased theta and delta power and decreased alpha and beta power, measured with quantitative electroencephalography (EEG), have been demonstrated to have utility for predicting the development of dementia in patients with Parkinson's disease (PD). Noradrenaline modulates cortical activity and optimizes cognitive processes. We claim that the loss of noradrenaline may explain cognitive impairment and the pathological slowing of EEG waves. Here, we test the relationship between the number of noradrenergic α2 adrenoceptors and changes in the spectral EEG ratio in patients with PD. METHODS: We included nineteen patients with PD and thirteen healthy control (HC) subjects in the study. We used positron emission tomography (PET) with [11C]yohimbine to quantify α2 adrenoceptor density. We used EEG power in the delta (δ, 1.5-3.9 Hz), theta (θ, 4-7.9 Hz), alpha (α, 8-12.9 Hz) and beta (ß, 13-30 Hz) bands in regression analyses to test the relationships between α2 adrenoceptor density and EEG band power. RESULTS: PD patients had higher power in the theta and delta bands compared to the HC volunteers. Patients' theta band power was inversely correlated with α2 adrenoceptor density in the frontal cortex. In the HC subjects, age was correlated with, and occipital background rhythm frequency (BRF) was inversely correlated with, α2 adrenoceptor density in the frontal cortex, while occipital BRF was inversely correlated with α2 adrenoceptor density in the thalamus. CONCLUSIONS: The findings support the claim that the loss or dysfunction of noradrenergic neurotransmission may relate to the parallel processes of cognitive decline and EEG slowing.