Glial pathology in Parkinson's disease : focus on microglia

Imperial Users onl

Microglial inflammation in the parkinsonian substantia nigra: relationship to alpha-synuclein deposition

BACKGROUND: The role of both microglial activation and alpha-synuclein deposition in Parkinson's disease remain unclear. We have tested the hypothesis that if microglia play a primary role in Parkinson's disease pathogenesis, the microglial "activated" phenotype should be associated with histopathological and/or clinical features of the disease. METHODS: We have examined microglial MHC class II expression, a widely used marker of microglial activation, the occurrence of CD68-positive phagocytes and alpha-synuclein immunoreactivity in post-mortem human substantia nigra affected by idiopathic Parkinson's disease (PD). Using semi-quantitative severity ratings, we have examined the relationship between microglial activation, alpha-synuclein deposition, classical neuropathological criteria for PD, subtype of the disease and clinical course. RESULTS: While we did not observe an association between microglial MHC class II expression and clinical parameters, we did find a correlation between disease duration and the macrophage marker CD68 which is expressed by phagocytic microglia. In addition, we observed a significant correlation between the degree of MHC class II expression and alpha-synuclein deposition in the substantia nigra in PD. CONCLUSION: While microglia appeared to respond to alpha-synuclein deposition, MHC class II antigen expression by microglia in the substantia nigra cannot be used as an indicator of clinical PD severity or disease progression. In addition, a contributory or even causative role for microglia in the neuronal loss associated with PD as suggested by some authors seems unlikely. Our data further suggest that an assessment of microglial activation in the aged brain on the basis of immunohistochemistry for MHC class II antigens alone should be done with caution

Back in time for breakfast: An analysis of the changing breakfast cereal aisle

Breakfast cereal improves overall diet quality yet is under constant scrutiny with assertions that the category has not improved over time. This study aimed to comprehensively analyse the category of breakfast cereals, the nutritional values, and health claims across eight distinct sub-categories at four time points (2013, 2015, 2018, and 2020). An audit of products from four major supermarkets in metropolitan Sydney (Aldi, Coles, IGA, and Woolworths) collected ingredient lists, nutrition information, claims and Health Star Rating (HSR) for biscuits and bites; brans; bubbles, puffs, and flakes; granola and clusters; hot cereal flavoured; hot cereal plain; muesli; breakfast biscuits. The median (IQR) were calculated for energy, protein, fat, saturated fat, carbohydrate, sugars, dietary fibre, and sodium for comparisons over time points by nutrient. Data from 2013 was compared with 2020 (by sub-category and then for a sub-section of common products available at each time point). Product numbers between 2013 (n = 283) and 2020 (n = 543) almost doubled, led by granola and clusters. Whole grain cereals ≥ 8 g/serve made up 67% of products (↑114%). While there were positive changes in nutrient composition over time within the full data set, the most notable changes were in the nutrition composition of cereals marketed as the same product in both years (n = 134); with decreases in mean carbohydrate (2%), sugar (10%) and sodium (16%) (p \u3c 0.000), while protein and total fat increased significantly (p = 0.036; p = 0.021). Claims regarding Dietary Fibre and Whole Grain doubled since 2013. Analysis of sub-categories of breakfast cereal assisted in identifying some changes over time, but products common to both timeframes provided a clearer analysis of change within the breakfast category, following introduction of HSR. Whole grain products were lower in the two target nutrients, sodium and sugars, and well-chosen products represent a better choice within this category

Assessing the concurrent validity and interrater reliability of patient-led screening using the malnutrition screening tool in the ambulatory cancer care outpatient setting

Background The prevalence of malnutrition in cancer patients is reported as high as 65%; however, malnutrition screening is often substandard. The Malnutrition Screening Tool (MST) has been validated for use by health care professionals to detect at -risk patients; however, there is a gap in the literature regarding validation of patient -led MST screening. Objective The aim of the study was to assess the concurrent validity of patient -led MST against the Subjective Global Assessment (SGA) and the interrater reliability of patient - led MST against dietitian -led MST in patients attending ambulatory cancer care services for chemotherapy or supportive treatments. Design/participants A single -site diagnostic accuracy study of 201 patients between May and June 2017 attending the ambulatory cancer care setting at an Australian metropolitan tertiary hospital in Queensland. Main outcome measurements The primary outcome measures were concurrent val- idity and interrater reliability of MST scores as determined by patients (patient -MST), dietitians (dietitian -MST), and SGA as completed by the dietitian. Statistical analysis Concurrent validity of patient -led MST scores against the SGA was determined using speci ficity, sensitivity, positive predictive values, and negative pre- dictive values. Interrater reliability of patient -MST and dietitian -MST was assessed using K coef ficient. Results The ability of the patient -led MST scores (0 to 1 vs 2 to 5) to indicate nutrition status was found to have a sensitivity of 94% (95% CI 81% to 99%), a speci ficity of 86% (95% CI 79% to 91%), and an area under the receiver operating characteristic curve of 0.93 (95% CI 0.89 to 0.96). The positive predictive value was 59% (95% CI 45% to 71%), and the negative predictive value was 99% (95% CI 95% to 100%). A weighted K of 0.83 (95% CI 0.82 to 0.87) between patient -MST and dietitian -MST was found. Conclusion Patient -led MST screening is a reliable and valid measure that can accu- rately identify ambulatory cancer care patients as at risk or not at risk of malnutrition. J Acad Nutr Diet. 2020;120(7):1210-1215

Relationship between isometric strength of 6 muscle groups of the lower limbs and motor skills among nursing home residents

peer reviewe

Physical abilities of elderly nursing home residents: The SENIOR cohort

peer reviewe

Mitochondrial RNA granules are fluid condensates positioned by membrane dynamics

Phase separation concentrates mitochondrial RNA granules. Here Rey et al., show that mitochondrial RNA granules (MRGs) behaviour is consistent with liquid-liquid phase separation (LLPS) and their fusion coincides with mitochondrial remodelling.Mitochondria contain the genetic information and expression machinery to produce essential respiratory chain proteins. Within the mitochondrial matrix, newly synthesized RNA, RNA processing proteins and mitoribosome assembly factors form punctate sub-compartments referred to as mitochondrial RNA granules (MRGs)(1-3). Despite their proposed importance in regulating gene expression, the structural and dynamic properties of MRGs remain largely unknown. We investigated the internal architecture of MRGs using fluorescence super-resolution localization microscopy and correlative electron microscopy, and found that the MRG ultrastructure consists of compacted RNA embedded within a protein cloud. Using live-cell super-resolution structured illumination microscopy and fluorescence recovery after photobleaching, we reveal that MRGs rapidly exchange components and can undergo fusion, characteristic properties of fluid condensates(4). Furthermore, MRGs associate with the inner mitochondrial membrane and their fusion coincides with mitochondrial remodelling. Inhibition of mitochondrial fission or fusion leads to an aberrant accumulation of MRGs into concentrated pockets, where they remain as distinct individual units despite their close apposition. Together, our findings reveal that MRGs are nanoscale fluid compartments, which are dispersed along mitochondria via membrane dynamics

Mutant Selection Window in Levofloxacin and Moxifloxacin Treatments of Experimental Pneumococcal Pneumonia in a Rabbit Model of Human Therapy

For some pneumococci the fluoroquinolone MICs are low but the mutant prevention concentrations (MPCs) are high; this difference defines in vitro the mutant selection window (MSW). We investigated in vivo the bacterial reduction and the occurrence of resistant mutants with moxifloxacin (MFX; 400 mg once daily) or levofloxacin (LVX; 500 mg twice daily) in treatments similar to those in humans with experimental pneumonia due to pneumococci (expPP) exhibiting various MICs and MPCs. The MIC/MPC for MFX and LVX and genotypes were as follows: strain 16089, 0.125/0.125 and 0.5/0.5 (wild type); strain MS1A, 0.25/0.25 and 1/2 (efflux); strain MS2A, 0.25/4 and 1.75/28 (parC79); strain MR3B4, 0.25/4 and 2/32 (parC79); strain M16, 0.5/2 and 8/32 (parC83); strain Gyr-1207, 1.5/3 and 8/16 (gyrA); and strain MQ3A, 4/4 and 16/64 (parC and gyrA). Both drugs were efficient with wild type-expPP, but only MFX was efficient with efflux-expPP. No bacterial reduction was observed for parC-expPPs due to mutants observed in 18 to 100% of animals, depending on the strain and the drug tested. These mutants showed unbound area under the concentration-time curve and MICs of from 50 to 164 for MFX. The in vivo pharmacodynamic boundaries of the MSW were different for MFX and LVX. We conclude that, after LVX or MFX treatment, mutants occur in vivo if there is a preexisting parC mutation, since the drug concentrations fall below the MPCs of these strains. Since the MPC determination cannot be routinely determined, these phenotypes or genotypes should be detected by simple tests to guide the therapeutic options