Automated, high accuracy classification of Parkinsonian disorders: a pattern recognition approach

Progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and idiopathic Parkinson’s disease (IPD) can be clinically indistinguishable, especially in the early stages, despite distinct patterns of molecular pathology. Structural neuroimaging holds promise for providing objective biomarkers for discriminating these diseases at the single subject level but all studies to date have reported incomplete separation of disease groups. In this study, we employed multi-class pattern recognition to assess the value of anatomical patterns derived from a widely available structural neuroimaging sequence for automated classification of these disorders. To achieve this, 17 patients with PSP, 14 with IPD and 19 with MSA were scanned using structural MRI along with 19 healthy controls (HCs). An advanced probabilistic pattern recognition approach was employed to evaluate the diagnostic value of several pre-defined anatomical patterns for discriminating the disorders, including: (i) a subcortical motor network; (ii) each of its component regions and (iii) the whole brain. All disease groups could be discriminated simultaneously with high accuracy using the subcortical motor network. The region providing the most accurate predictions overall was the midbrain/brainstem, which discriminated all disease groups from one another and from HCs. The subcortical network also produced more accurate predictions than the whole brain and all of its constituent regions. PSP was accurately predicted from the midbrain/brainstem, cerebellum and all basal ganglia compartments; MSA from the midbrain/brainstem and cerebellum and IPD from the midbrain/brainstem only. This study demonstrates that automated analysis of structural MRI can accurately predict diagnosis in individual patients with Parkinsonian disorders, and identifies distinct patterns of regional atrophy particularly useful for this process

Implementing chemical functionality into oriented films of metal–organic frameworks on self-assembled monolayers

The generation of thin films of oriented functionalized metal–organic frameworks (MOFs) on self-assembled monolayers was achieved via direct growth from solution. Specifically, the direct growth from solvothermally pretreated synthesis solutions of two different MOF structures with amino functionality was investigated: the flexible framework structure NH2–Fe–MIL-88B and the mesoporous MOF NH2–Fe–MIL-101 with its remarkably large unit cell. Both MOF structures can be grown in a highly oriented fashion on self-assembled monolayers of 16-mercaptohexadecanoic acid on gold. With the help of a quartz crystal microbalance we demonstrate that the introduction of amino groups into the framework strongly affects the host–guest interactions towards ethanol molecules: thin films of NH2–Fe–MIL-88B show a significantly higher uptake of ethanol than unfunctionalized Fe–MIL-88B films. In situ XRD experiments during sorption of ethanol showed that the amino group does have an impact on the cell parameters of the structure, but the flexibility ("breathing") during ad- and desorption of ethanol is similar for the functionalized and the unfunctionalized structures. It is anticipated that the implementation of chemical functionalities into oriented MOF films will lead to selective host–guest interactions that are of key importance for chemical sensing and other applications

Cortical thickness, surface area and volume measures in Parkinson's disease, multiple system atrophy and progressive supranuclear palsy

OBJECTIVE Parkinson's disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) are neurodegenerative diseases that can be difficult to distinguish clinically. The objective of the current study was to use surface-based analysis techniques to assess cortical thickness, surface area and grey matter volume to identify unique morphological patterns of cortical atrophy in PD, MSA and PSP and to relate these patterns of change to disease duration and clinical features. METHODS High resolution 3D T1-weighted MRI volumes were acquired from 14 PD patients, 18 MSA, 14 PSP and 19 healthy control participants. Cortical thickness, surface area and volume analyses were carried out using the automated surface-based analysis package FreeSurfer (version 5.1.0). Measures of disease severity and duration were assessed for correlation with cortical morphometric changes in each clinical group. RESULTS Results show that in PSP, widespread cortical thinning and volume loss occurs within the frontal lobe, particularly the superior frontal gyrus. In addition, PSP patients also displayed increased surface area in the pericalcarine. In comparison, PD and MSA did not display significant changes in cortical morphology. CONCLUSION These results demonstrate that patients with clinically established PSP exhibit distinct patterns of cortical atrophy, particularly affecting the frontal lobe. These results could be used in the future to develop a useful clinical application of MRI to distinguish PSP patients from PD and MSA patients

Diffusion tensor imaging of Parkinson's disease, multiple system atrophy and progressive supranuclear palsy: a tract-based spatial statistics study

Although often clinically indistinguishable in the early stages, Parkinson's disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) have distinct neuropathological changes. The aim of the current study was to identify white matter tract neurodegeneration characteristic of each of the three syndromes. Tract-based spatial statistics (TBSS) was used to perform a whole-brain automated analysis of diffusion tensor imaging (DTI) data to compare differences in fractional anisotropy (FA) and mean diffusivity (MD) between the three clinical groups and healthy control subjects. Further analyses were conducted to assess the relationship between these putative indices of white matter microstructure and clinical measures of disease severity and symptoms. In PSP, relative to controls, changes in DTI indices consistent with white matter tract degeneration were identified in the corpus callosum, corona radiata, corticospinal tract, superior longitudinal fasciculus, anterior thalamic radiation, superior cerebellar peduncle, medial lemniscus, retrolenticular and anterior limb of the internal capsule, cerebral peduncle and external capsule bilaterally, as well as the left posterior limb of the internal capsule and the right posterior thalamic radiation. MSA patients also displayed differences in the body of the corpus callosum corticospinal tract, cerebellar peduncle, medial lemniscus, anterior and superior corona radiata, posterior limb of the internal capsule external capsule and cerebral peduncle bilaterally, as well as the left anterior limb of the internal capsule and the left anterior thalamic radiation. No significant white matter abnormalities were observed in the PD group. Across groups, MD correlated positively with disease severity in all major white matter tracts. These results show widespread changes in white matter tracts in both PSP and MSA patients, even at a mid-point in the disease process, which are not found in patients with PD

Measurement of CD4+ and CD8+ T-Lymphocyte Cytokine Secretion and Gene Expression Changes in p-Phenylenediamine Allergic Patients and Tolerant Individuals

Factors predisposing to individual susceptibility to contact allergic dermatitis are ill defined. This study was designed to characterize the response of allergic and tolerant individuals’ T-lymphocytes after exposure to p-phenylenediamine (PPD). Peripheral blood mononuclear cells (PBMCs) from allergic patients proliferated when treated with PPD and Bandrowski's base (BB) and secreted IL-1α, -1β, -4, -5, -6, -8, -10, and -13; IFN-γ; tumor necrosis factor-α; MIP-1α/β; MCP-1 (monocyte chemotactic protein-1); and RANTES. PBMCs from tolerant individuals were stimulated to proliferate only with BB, and they secreted significantly lower levels of Th2 cytokines. Principal component analysis showed that genes are differentially expressed between the patient groups. A network-based analysis of microarray data showed upregulation of T helper type 2 (Th2) gene pathways, including IL-9, in allergic patients, but a regulatory gene profile in tolerant individuals. Real-time PCR confirmed the observed increase in Th2 cytokine gene transcription in allergic patients. Purified CD4+ and CD8+ T cells from allergic patients were stimulated to proliferate and secrete Th2 cytokines following antigen exposure. Only CD4+ T cells from tolerant individuals were stimulated by BB, and levels of Th2 cytokines were 80% lower. The nature of the antigenic determinant stimulating PBMCs and levels of Th2 cytokines, including IL-9, was confirmed in a validation cohort. These studies show increased activity of Th2 cytokines in CD4+ and CD8+ T cells from individuals with allergic contact dermatitis

Diagnostics to Support Elimination of Lymphatic Filariasis-Development of Two Target Product Profiles

As lymphatic filariasis (LF) programs move closer to established targets for validation elimination of LF as a public health problem, diagnostic tools capable of supporting the needs of the programs are critical for success. Known limitations of existing diagnostic tools make it challenging to have confidence that program endpoints have been achieved. In 2019, the World Health Organization (WHO) established a Diagnostic Technical Advisory Group (DTAG) for Neglected Tropical Diseases tasked with prioritizing diagnostic needs including defining use-cases and target product profiles (TPPs) for needed tools. Subsequently, disease-specific DTAG subgroups, including one focused on LF, were established to develop TPPs and use-case analyses to be used by product developers. Here, we describe the development of two priority TPPs for LF diagnostics needed for making decisions for stopping mass drug administration (MDA) of a triple drug regimen and surveillance. Utilizing the WHO core TPP development process as the framework, the LF subgroup convened to discuss and determine attributes required for each use case. TPPs considered the following parameters: Product use, design, performance, product configuration and cost, and access and equity. Version 1.0 TPPs for two use cases were published by WHO on 12 March 2021 within the WHO Global Observatory on Health Research and Development. A common TPP characteristic that emerged in both use cases was the need to identify new biomarkers that would allow for greater precision in program delivery. As LF diagnostic tests are rarely used for individual clinical diagnosis, it became apparent that reliance on population-based surveys for decision making requires consideration of test performance in the context of such surveys. In low prevalence settings, the number of false positive test results may lead to unnecessary continuation or resumption of MDA, thus wasting valuable resources and time. Therefore, highly specific diagnostic tools are paramount when used to measure low thresholds. The TPP process brought to the forefront the importance of linking use case, program platform and diagnostic performance characteristics when defining required criteria for diagnostic tools

Isolation of Angola-like Marburg virus from Egyptian rousette bats from West Africa.

Marburg virus (MARV) causes sporadic outbreaks of severe Marburg virus disease (MVD). Most MVD outbreaks originated in East Africa and field studies in East Africa, South Africa, Zambia, and Gabon identified the Egyptian rousette bat (ERB; Rousettus aegyptiacus) as a natural reservoir. However, the largest recorded MVD outbreak with the highest case-fatality ratio happened in 2005 in Angola, where direct spillover from bats was not  shown. Here, collaborative studies by the Centers for Disease Control and Prevention, Njala University, University of California, Davis USAID-PREDICT, and the University of Makeni identify MARV circulating in ERBs in Sierra Leone. PCR, antibody and virus isolation data from 1755 bats of 42 species shows active MARV infection in approximately 2.5% of ERBs. Phylogenetic analysis identifies MARVs that are similar to the Angola strain. These results provide evidence of MARV circulation in West Africa and demonstrate the value of pathogen surveillance to identify previously undetected threats

"I could cry, the amount of shoes I can't get into": A qualitative exploration of the factors that influence retail footwear selection in women with rheumatoid arthritis

<p>Abstract</p> <p>Background</p> <p>Studies have reported that women with rheumatoid arthritis (RA) are not wearing NHS supplied therapeutic footwear; therefore it is likely they are wearing footwear sourced through retailers. Previous research gives limited information (largely associated with cosmesis) on people's perceptions on the relationships that exist between retail footwear, well-being and quality of life. This study aimed to explore the perceptions of women with RA regarding their choice of retail footwear and identify the factors influencing retail footwear selection.</p> <p>Methods</p> <p>Eleven women with RA wearing normal retail footwear were recruited from an out-patient podiatry clinic in the south east of England. Semi-structured interviews were carried out and an interpretative phenomenological approach was adopted for data collection and transcript analysis.</p> <p>Results</p> <p>Six key themes were revealed from the analysis: (1) the nature of foot complaints and deformities, (2) aesthetic appearance and design of footwear, (3) body image, (4) psychosocial aspects, (5) Perceptions of footwear and (6) the therapeutic value of retail shoes. These contributed to an overarching concept of loss of choice associated with retail footwear. In particular, the areas discussed most frequently throughout were themes (2), (3) and (4), which were notably more 'emotional' in nature.</p> <p>Conclusions</p> <p>Limitations in retail footwear for these women have impacted on their individuality, linking significantly with their body image. The loss of choice in footwear as a consequence of the disease impacts negatively on emotions, wellbeing and was identified in reduced self-perceived quality of life.</p