Cholinergic white matter pathways along the Alzheimer's disease continuum.

Previous studies have shown that the cholinergic nucleus basalis of Meynert and its white matter projections are affected in Alzheimer's disease dementia and mild cognitive impairment. However, it is still unknown whether these alterations can be found in individuals with subjective cognitive decline, and whether they are more pronounced than changes found in conventional brain volumetric measurements. To address these questions, we investigated microstructural alterations of two major cholinergic pathways in individuals along the Alzheimer's disease continuum using an in vivo model of the human cholinergic system based on neuroimaging. We included 402 participants (52 Alzheimer's disease, 66 mild cognitive impairment, 172 subjective cognitive decline and 112 healthy controls) from the Deutsches Zentrum für Neurodegenerative Erkrankungen Longitudinal Cognitive Impairment and Dementia Study. We modelled the cholinergic white matter pathways with an enhanced diffusion neuroimaging pipeline that included probabilistic fibre-tracking methods and prior anatomical knowledge. The integrity of the cholinergic white matter pathways was compared between stages of the Alzheimer's disease continuum, in the whole cohort and in a CSF amyloid-beta stratified subsample. The discriminative power of the integrity of the pathways was compared to the conventional volumetric measures of hippocampus and nucleus basalis of Meynert, using a receiver operating characteristics analysis. A multivariate model was used to investigate the role of these pathways in relation to cognitive performance. We found that the integrity of the cholinergic white matter pathways was significantly reduced in all stages of the Alzheimer's disease continuum, including individuals with subjective cognitive decline. The differences involved posterior cholinergic white matter in the subjective cognitive decline stage and extended to anterior frontal white matter in mild cognitive impairment and Alzheimer's disease dementia stages. Both cholinergic pathways and conventional volumetric measures showed higher predictive power in the more advanced stages of the disease, i.e. mild cognitive impairment and Alzheimer's disease dementia. In contrast, the integrity of cholinergic pathways was more informative in distinguishing subjective cognitive decline from healthy controls, as compared with the volumetric measures. The multivariate model revealed a moderate contribution of the cholinergic white matter pathways but not of volumetric measures towards memory tests in the subjective cognitive decline and mild cognitive impairment stages. In conclusion, we demonstrated that cholinergic white matter pathways are altered already in subjective cognitive decline individuals, preceding the more widespread alterations found in mild cognitive impairment and Alzheimer's disease. The integrity of the cholinergic pathways identified the early stages of Alzheimer's disease better than conventional volumetric measures such as hippocampal volume or volume of cholinergic nucleus basalis of Meynert.

Cholinergic white matter pathways make a stronger contribution to attention and memory in normal aging than cerebrovascular health and nucleus basalis of Meynert.

The integrity of the cholinergic system plays a central role in cognitive decline both in normal aging and neurological disorders including Alzheimer's disease and vascular cognitive impairment. Most of the previous neuroimaging research has focused on the integrity of the cholinergic basal forebrain, or its sub-region the nucleus basalis of Meynert (NBM). Tractography using diffusion tensor imaging data may enable modelling of the NBM white matter projections. We investigated the contribution of NBM volume, NBM white matter projections, small vessel disease (SVD), and age to performance in attention and memory in 262 cognitively normal individuals (39-77 years of age, 53% female). We developed a multimodal MRI pipeline for NBM segmentation and diffusion-based tracking of NBM white matter projections, and computed white matter hypointensities (WM-hypo) as a marker of SVD. We successfully tracked pathways that closely resemble the spatial layout of the cholinergic system as seen in previous post-mortem and DTI tractography studies. We found that high WM-hypo load was associated with older age, male sex, and lower performance in attention and memory. A high WM-hypo load was also associated with lower integrity of the cholinergic system above and beyond the effect of age. In a multivariate model, age and integrity of NBM white matter projections were stronger contributors than WM-hypo load and NBM volume to performance in attention and memory. We conclude that the integrity of NBM white matter projections plays a fundamental role in cognitive aging. This and other modern neuroimaging methods offer new opportunities to re-evaluate the cholinergic hypothesis of cognitive aging.

Staff perspectives on the usability of electronic patient records for planning and delivering dementia care in nursing homes: a multiple case study.

BACKGROUND: The electronic patient record (EPR) has been introduced into nursing homes in order to facilitate documentation practices such as assessment and care planning, which play an integral role in the provision of dementia care. However, little is known about how the EPR facilitates or hinders these practices from the end-user's perspective. Therefore, the objective of this qualitative study was to explore the usability issues associated with the EPR for assessment and care planning for people with dementia in nursing homes from a staff perspective. METHODS: An exploratory, qualitative research design with a multiple case study approach was used. Contextual Inquiry was carried out with a variety of staff members (n = 21) who used the EPR in three nursing homes situated in Belgium, Czech Republic and Spain. Thematic analysis was used to code interview data, with codes then sorted into a priori components of the Health Information Technology Evaluation Framework: device, software functionality, organisational support. Two additional themes, structure and content, were also added. RESULTS: Staff provided numerous examples of the ways in which EPR systems are facilitating and hindering assessment and care planning under each component, particularly for people with dementia, who may have more complex needs in comparison to other residents. The way in which EPR systems were not customisable was a common theme across all three homes. A comparison of organisational policies and practices revealed the importance of training, system support, and access, which may be linked with the successful adoption of the EPR system in nursing homes. CONCLUSIONS: EPR systems introduced into the nursing home environment should be customisable and reflect best practice guidelines for dementia care, which may lead to improved outcomes and quality of life for people with dementia living in nursing homes. All levels of nursing home staff should be consulted during the development, implementation and evaluation of EPR systems as part of an iterative, user-centred design process.

Electrochemical Sensors and Biosensors for Identification of Viruses: A Critical Review.

Due to their life cycle, viruses can disrupt the metabolism of their hosts, causing diseases. If we want to disrupt their life cycle, it is necessary to identify their presence. For this purpose, it is possible to use several molecular-biological and bioanalytical methods. The reference selection was performed based on electronic databases (2020-2023). This review focused on electrochemical methods with high sensitivity and selectivity (53% voltammetry/amperometry, 33% impedance, and 12% other methods) which showed their great potential for detecting various viruses. Moreover, the aforementioned electrochemical methods have considerable potential to be applicable for care-point use as they are portable due to their miniaturizability and fast speed analysis (minutes to hours), and are relatively easy to interpret. A total of 2011 articles were found, of which 86 original papers were subsequently evaluated (the majority of which are focused on human pathogens, whereas articles dealing with plant pathogens are in the minority). Thirty-two species of viruses were included in the evaluation. It was found that most of the examined research studies (77%) used nanotechnological modifications. Other ones performed immunological (52%) or genetic analyses (43%) for virus detection. 5% of the reports used peptides to increase the method's sensitivity. When evaluable, 65% of the research studies had LOD values in the order of ng or nM. The vast majority (79%) of the studies represent proof of concept and possibilities with low application potential and a high need of further research experimental work.

Use of brightness wavelet transformation for automated analysis of serum metallothioneins- and zinc-containing proteins by Western blots to subclassify childhood solid tumours.

In this study, we determined serum levels of metallothioneins (MTs) and zinc in children with solid tumours (neuroblastoma, Hodgkin lymphoma, medulloblastoma, osteosarcoma, Ewing sarcoma and nephroblastoma) by differential pulse voltammetry Brdicka reaction and ELISA. Zn(II) level in patients sera was 40% compared to controls, contrariwise, MT level was 4.2 × higher in patients. No significant differences among single diagnoses were found both for Zn(II) and MT. When determined Zn(II)/MT ratio, in controls its value was 24.6, but it was 2.6 in patients. After Western-blotting with anti-MT and anti-Zn chicken antibodies, variable intensities of the bands within the samples were observed. The brightness curve obtained for each sample both for MT- and Zn blots was further analysed to produce a list of band positions together with some complementary information related to the intensity of the observed bands by the optimised algorithm. We constructed from those profiles decision trees that enable to distinguish different groups of tumours. The blood samples were heat-treated, in which we supposed mainly MT, but samples contained other thermostable Zn-containing proteins that were helpful for identification of embryonal tumours with 88% accuracy and for identification of sarcomas with 78% accuracy. In MT blots the accuracies were 53 and 45%, respectively. Simultaneous analysis of MT and Zn blots did not increased accuracy of identification neither in embryonal tumours (80%) nor in sarcomas. Those results are promising not only from diagnostic point of view but particularly in the area of studying of individual MT isoforms and their aggregates in malignant tumours.

Modeling intrinsic factors of inclusive engagement in citizen science: Insights from the participants' survey analysis of CSI-COP.

Inclusive citizen science, an emerging field, has seen extensive research. Prior studies primarily concentrated on creating theoretical models and practical strategies for diversifying citizen science (CS) projects. These studies relied on ethical frameworks or post-project empirical observations. Few examined active participants' socio-demographic and behavioral data. Notably, none, to our knowledge, explored prospective citizen scientists' traits as intrinsic factors to enhance diversity and engagement in CS. This paper presents a new inclusive CS engagement model based on quantitative analysis of surveys administered to 540 participants of the dedicated free informal education MOOC (Massive Open Online Course) 'Your Right to Privacy Online' from eight countries in the EU funded project, CSI-COP (Citizen Scientists Investigating Cookies and App GDPR compliance). The surveys were filled out just after completing the training stage and before joining the project as active CSs. Out of the 540 participants who completed the surveys analyzed in this study, only 170 (32%) individuals actively participated as CSs in the project. Therefore, the study attempted to understand what characterizes these participants compared to those who decided to refrain from joining the project after the training stage. The study employed descriptive analysis and advanced statistical tests to explore the correlations among different research variables. The findings revealed several important relationships and predictors for becoming a citizen scientist based on the surveys analysis, such as age, gender, culture, education, Internet accessibility and apps usage, as well as the satisfaction with the MOOC, the mode of training and initial intentions for becoming a CS. These findings lead to the development of the empirical model for inclusive engagement in CS and enhance the understanding of the internal factors that influence individuals' intention and actual participation as CSs. The devised model offers valuable insights and key implications for future CS initiatives. It emphasizes the necessity of targeted recruitment strategies, focusing on underrepresented groups and overcoming accessibility barriers. Positive learning experiences, especially through MOOCs, are crucial; enhancing training programs and making educational materials accessible and culturally diverse can boost participant motivation. Acknowledging varying technological proficiency and providing necessary resources enhances active engagement. Addressing the intention-engagement gap is vital; understanding underlying factors and creating supportive environments can transform intentions into active involvement. Embracing cultural diversity through language-specific strategies ensures an inclusive environment for effective contributions.

Association of Cerebrovascular and Alzheimer Disease Biomarkers With Cholinergic White Matter Degeneration in Cognitively Unimpaired Individuals.

BACKGROUND AND OBJECTIVES: Several pathologic processes might contribute to the degeneration of the cholinergic system in aging. We aimed to determine the contribution of amyloid, tau, and cerebrovascular biomarkers toward the degeneration of cholinergic white matter (WM) projections in cognitively unimpaired individuals. METHODS: The contribution of amyloid and tau pathology was assessed through CSF levels of the Aß42/40 ratio and phosphorylated tau (p-tau). CSF Aß38 levels were also measured. Cerebrovascular pathology was assessed using automatic segmentations of WM lesions (WMLs) on MRI. Cholinergic WM projections (i.e., cingulum and external capsule pathways) were modeled using tractography based on diffusion tensor imaging data. Sex and APOE ε4 carriership were also included in the analysis as variables of interest. RESULTS: We included 203 cognitively unimpaired individuals from the H70 Gothenburg Birth Cohort Studies (all individuals aged 70 years, 51% female). WM lesion burden was the most important contributor to the degeneration of both cholinergic pathways (increase in mean square error [IncMSE] = 98.8% in the external capsule pathway and IncMSE = 93.3% in the cingulum pathway). Levels of Aß38 and p-tau also contributed to cholinergic WM degeneration, especially in the external capsule pathway (IncMSE = 28.4% and IncMSE = 23.4%, respectively). The Aß42/40 ratio did not contribute notably to the models (IncMSE<3.0%). APOE ε4 carriers showed poorer integrity in the cingulum pathway (IncMSE = 21.33%). Women showed poorer integrity of the external capsule pathway (IncMSE = 21.55%), which was independent of amyloid status as reflected by the nonsignificant differences in integrity when comparing amyloid-positive vs amyloid-negative women participants (T201 = -1.55; p = 0.123). DISCUSSION: In cognitively unimpaired older individuals, WMLs play a central role in the degeneration of cholinergic pathways. Our findings highlight the importance of WM lesion burden in the elderly population, which should be considered in the development of prevention programs for neurodegeneration and cognitive impairment.

Perspectives on Open Science and The Future of Scholarly Communication: Internet Trackers and Algorithmic Persuasion.

The current digital content industry is heavily oriented towards building platforms that track users' behaviour and seek to convince them to stay longer and come back sooner onto the platform. Similarly, authors are incentivised to publish more and to become champions of dissemination. Arguably, these incentive systems are built around public reputation supported by a system of metrics, hard to be assessed. Generally, the digital content industry is permeable to non-human contributors (algorithms that are able to generate content and reactions), anonymity and identity fraud. It is pertinent to present a perspective paper about early signs of track and persuasion in scholarly communication. Building our views, we have run a pilot study to determine the opportunity for conducting research about the use of "track and persuade" technologies in scholarly communication. We collected observations on a sample of 148 relevant websites and we interviewed 15 that are experts related to the field. Through this work, we tried to identify 1) the essential questions that could inspire proper research, 2) good practices to be recommended for future research, and 3) whether citizen science is a suitable approach to further research in this field. The findings could contribute to determining a broader solution for building trust and infrastructure in scholarly communication. The principles of Open Science will be used as a framework to see if they offer insights into this work going forward.

Electronic patient records as a tool to facilitate care provision in nursing homes: an integrative review.

Objective: The electronic patient record (EPR) has been introduced into nursing homes with the aim of reducing time spent on documentation, improving documentation quality and increasing transferability of information, all of which should facilitate care provision. However, previous research has shown that EPR may be creating new burdens for staff. The purpose of this literature review is to explore how EPR is facilitating or hindering care provision in nursing homes. Methods: An integrative literature review was carried out using four electronic databases to search for relevant articles. After screening, 22 articles were included for thematic synthesis. Results: Thematic synthesis resulted in six analytical themes linked to care provision: time for direct care; accountability; assessment and care planning; exchange of information; risk awareness; and person-centered care. Conclusion: For EPR to facilitate care provision in nursing homes, consideration should be given to the type of device used for documentation, as well as the types of applications, the functionality, content, and structure of EPR. Further research exploring the experiences of end users is required to identify the optimal characteristics of an EPR system specifically for use in nursing homes.

Spatial mapping of metals in tissue-sections using combination of mass-spectrometry and histology through image registration.

We describe a new procedure for the parallel mapping of selected metals in histologically characterized tissue samples. Mapping is achieved via image registration of digital data obtained from two neighbouring cryosections by scanning the first as a histological sample and subjecting the second to laser ablation inductively coupled plasma mass spectrometry. This computer supported procedure enables determination of the distribution and content of metals of interest directly in the chosen histological zones and represents a substantial improvement over the standard approach, which determines these values in tissue homogenates or whole tissue sections. The potential of the described procedure was demonstrated in a pilot study that analysed Zn and Cu levels in successive development stages of pig melanoma tissue using MeLiM (Melanoma-bearing-Libechov-Minipig) model. We anticipate that the procedure could be useful for a complex understanding of the role that the spatial distribution of metals plays within tissues affected by pathological states including cancer.

Differences in urinary proteins related to surgical margin status after radical prostatectomy.

Presented exploratory pilot study was aimed at evaluation of proteins present in urinary specimens collected from prostate cancer suffering subjects after radical prostatectomy, divided into two experimental cohorts: positive (n=15) and negative (n=15) surgical margins (PSM/NSM). The presence of PSM suggests inadequate cancer clearance and the possible need for additional treatment. Proper identification of these risk-patients is therefore of a paramount importance. Total protein profiles were firstly identified by using SDS-PAGE and compared by using partial least square discrimination analysis (PLS-DA), which revealed differences in molecular weights of 80-99 and 150-235 kDa between the experimental groups. For further identification of proteins, comparative proteomic technologies were employed. Two-dimensional gel electrophoresis with subsequent identification of protein spots by using MALDI-TOF mass fingerprinting revealed differential expression of proteins between NSM/PSM cohorts. Moreover, in PSM group, three uniquely identified proteins (cyclin-dependent kinase 6, galectin-3-binding protein and L-lactate dehydrogenase C chain) were found, which show tight connection with prostate cancer and presence of all of them was previously linked to certain aspects of prostate cancer. These proteins may be associated with the molecular mechanisms of prostate cancer development; hence, their identification may be helpful for the assessment of disease progression risk after radical prostatectomy, but also for possible early diagnosis.

Tissue specific electrochemical fingerprinting.

BACKGROUND: Proteomics and metalloproteomics are rapidly developing interdisciplinary fields providing enormous amounts of data to be classified, evaluated and interpreted. Approaches offered by bioinformatics and also by biostatistical data analysis and treatment are therefore of extreme interest. Numerous methods are now available as commercial or open source tools for data processing and modelling ready to support the analysis of various datasets. The analysis of scientific data remains a big challenge, because each new task sets its specific requirements and constraints that call for the design of a targeted data pre-processing approach. METHODOLOGY/PRINCIPAL FINDINGS: This study proposes a mathematical approach for evaluating and classifying datasets obtained by electrochemical analysis of metallothionein in rat 9 tissues (brain, heart, kidney, eye, spleen, gonad, blood, liver and femoral muscle). Tissue extracts were heated and then analysed using the differential pulse voltammetry Brdicka reaction. The voltammograms were subsequently processed. Classification models were designed making separate use of two groups of attributes, namely attributes describing local extremes, and derived attributes resulting from the level=5 wavelet transform. CONCLUSIONS/SIGNIFICANCE: On the basis of our results, we were able to construct a decision tree that makes it possible to distinguish among electrochemical analysis data resulting from measurements of all the considered tissues. In other words, we found a way to classify an unknown rat tissue based on electrochemical analysis of the metallothionein in this tissue.

Comparative study of non-invasive blood pressure measurement methods in elderly people.

Results obtained by the modern automatic blood pressure (BP) monitors using oscillometric method [5] are highly dependent on conditions of cardiovascular system of the monitored person. Especially, with people who suffer from cardiovascular diseases (e.g. atherosclerosis) the resulting values differ significantly from those measured by the traditional auscultation method. A reasonable solution for improvement of quality of oscillometric method could be a sophisticated intelligent BP measuring system which applies for evaluation of BP more complex approach taking into account the monitored person's condition of patient cardiovascular system (CS) i.e. the hemodynamic parameters of CS (e.g. heart rate, stroke volume, total peripheral resistance, systemic arterial compliance, pulse wave velocity, augmentation index etc.). Such a system has to be based on appropriate models of the considered diseases which are validated on real life data. For that purpose, we have started to build a database of real-life oscillometric pulsations waveforms (OPW) complemented by the values of "auscultation" blood pressure measurements and additional relevant information about the considered patients (age, sex, etc.) as well as their diagnosis. This data collection requires a special HW device for measurement of the OPW--we have developed such a device and it has been validated in Czech Certified Metrological Centre. Our OPW monitor is connected through the T-pieces and tubes to the cuff, mercury sphygmomanometer and automatic "oscillometric" blood pressure monitor.