Comparison of autonomic dysfunction in patients with Parkinson’s Disease, progressive supranuclear palsy, and multiple system atrophy

Aim of the study. To assess and compare autonomic nervous system (ANS) dysfunction, especially cardiovascular dysautonomia, in Parkinson’s Disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and healthy controls.Clinical rationale for the study. Assessment of ANS can be useful in differential diagnosis. Dysautonomia affects quality of life and can lead to potentially life-threatening complications. There is very little literature data regarding dysautonomia in PSP in relation to other parkinsonian syndromes. This study expands the knowledge about ANS dysfunction in parkinsonisms, especially PSP.Material and methods. Patients with PD, MSA and PSP were prospectively recruited to our study. Demographic data and information about clinical and neuropsychological assessment, medication and comorbidities was collected. SCOPA-AUT questionnaire, 5-minute tilt test, and 5-minute heart rate variability (HRV) analysis in time and frequency domains were used to assess ANS. Analysis was also performed in patients with PSP-RS and PSP-P phenotypes, and in a subgroup with eliminated confounding factors, including age and disease duration.Results. 76 PD, 25 PSP, and 12 MSA patients, and 20 controls, were included. Symptoms of dysautonomia revealed by a SCOPA-AUT questionnaire were present in all groups of patients. Urinary dysfunction was more pronounced in atypical parkinsonisms, and cardiovascular symptoms in α-synucleinopathies. HRV was disrupted in all groups of patients. However, when PSP-P and PSP-RS phenotypes were considered, HRV was diminished in PSP-RS, but there were no differences in HRV parameters between PSP-P and controls. Neurogenic orthostatic hypotension was present in 25% of PD and 58% of MSA patients, but it was absent in PSP patients and the control group. 13 PD and nine PSP patients and 16 controls were included in subanalysis. This revealed that PSP, but not PD, patients had significantly more symptoms of dysautonomia and lower HRV indices compared to controls, and that orthostatic hypotension was even more common in PD than in controls.Conclusions and clinical implications. Our study suggests that dysautonomia is common in PD, MSA and PSP, even though it has different profiles in the different diseases. NOH is present in PD and MSA, but not in PSP

Mogućnost uporabe melamin-ureaformaldehidnog ljepila ojačanog nanocelulozom u proizvodnji furnirskih ploča

The possibility of using nanocellulose (NCC) as a filling substance for melamine-urea-formaldehyde (MUF) adhesive was investigated for the process of manufacturing plywood. The adhesive mixtures were prepared with various nanocellulose concentrations. The amount of introduced filler had a significant effect on both resin and plywood characteristics. Fourier transform infrared spectroscopy (FTIR) did not show any major changes between experimental and reference variants. The viscosity of resin increased after the introduction of nanocellulose. The addition of NCC in the amount of 5 g and 10 g per 100 g of solid resin led to an improvement in bonding quality, modulus of elasticity and bending strength. Further increase of NCC concentration caused a deterioration of manufactured plywood properties. In summary, the addition of proper amount of nanocellulose resulted in manufacturing plywood with improved properties.U radu je prikazano istraživanje mogućnosti uporabe nanoceluloze (NCC) kao punila za melaminurea-formaldehidno ljepilo (MUF) koje se upotrebljava u proizvodnji furnirskih ploča. Smjese ljepila pripremljene su dodavanjem različitih koncentracija nanoceluloze. Količina dodanog punila znatno je utjecala na svojstva smole i furnirske ploče. Furierovom infracrvenom spektroskopijom (FTIR) nisu utvrđene veće promjene između eksperimentalnih i referentnih varijanti. Viskoznost smole povećala se nakon dodatka nanoceluloze. Dodatak 5 i 10 g nanoceluloze na 100 g otvrdnute smole rezultirao je poboljšanjem kvalitete vezanja, modula elastičnosti i čvrstoće na savijanje. Daljnje povećanje koncentracije nanoceluloze uzrokovalo je pogoršanje svojstava proizvedenih furnirskih ploča. Ukratko, dodatak odgovarajuće količine nanoceluloze rezultirao je furnirskom pločom poboljšanih svojstava

Cognitive impairment and BDNF serum levels

Background/aims To investigate the alterations of brain-derived neurotrophic factor (BNDF) serum levels in subjects with different intensity of cognitive impairment and different neurodegenerative processes. Material and methods Serum BDNF levels were analyzed by ELISA kit in 378 subjects: 134 Alzheimer's disease (AD) patients, 115 amnestic mild cognitive impairment (MCI) patients, and 129 controls divided into two groups: neurodegenerative control group (ND), consisting of 49 Parkinson's disease patients without any cognitive complaints, and cognitively normal control group (CN), consisting of 80 subjects without any neurological disorders. Results AD patients had significantly lower (p<0.001) BDNF serum levels compared to MCI, CN and ND controls. Age and education had significant influence on BDNF serum levels regardless the diagnosis or group assignment. We have found no influence of depression on BDNF serum levels either in our group as a whole, or in each group assessed separately. We found significant correlation between BDNF serum levels and cognitive impairments. After multiple comparisons between the groups, we found that, after adjustment for confounding factors (age, gender, education, depression, cognitive impairment), BDNF serum levels were the lowest in AD group (p=0.05). Conclusions Advanced age and low educational level are associated with decreased BDNF serum levels. Decreased BDNF serum levels correspond to the severity of cognitive impairment. There is no correlation between BDNF serum levels and depressive symptoms

Risk factors for dementia in Parkinson’s Disease — the overuse of anticholinergic drugs

Aim of the study. To determine the risk factors for dementia in a group of patients with Parkinson’s Disease (PD), especially the effect of the anticholinergic burden assessed according to the Anticholinergic Cognitive Burden scale (ACB) and the CRIDECO Anticholinergic Load Scale (CALS). Clinical rationale for the study. To provide information about factors associated with Parkinson’s Disease dementia (PDD), especially the anticholinergic burden and testing the effect of both scales in an assessment of the anticholinergic burden in this group of patients. Material and methods. A retrospective and cross-sectional analysis of medical records of patients with Parkinson’s Disease admitted to the Neurology Department of the Medical University of Silesia, Katowice, Poland between 2019 and 2021 was performed. We found 418 patients with a diagnosis of PD, but 80 were excluded due to lack of a cognitive function assessment. Based on MMSE score, the remaining 338 patients were divided into two groups of patients with, and without, PDD. Next, demographic and clinical data was collected. The anticholinergic burden was assessed using the ACB and the CALS scales. According to the authors of these scales, : if a scale score is of three or more points, this should be considered as a significant anticholinergic burden. Multiple logistic regression with backward elimination was used to assess factors significantly related to the presence of dementia, and two different models were used for both scales assessing the anticholinergic burden. Results. 62 (18.3%) patients were diagnosed with PDD. Overall significant anticholinergic burden (≥ 3 points) was found in 31.95% of patients using CALS and in 18.93% using ACB. Anticholinergic burden was higher in patients with dementia (CALS 50 vs. 27.90%, p < 0.001, ACB 43.5 vs. 13.41%, p < 0.001). According to both models, the factors significantly related to dementia were: age (ACB OR 1,114 (1.062–1.170), p < 0.001, CALS OR 1.123 (1.070–1.178), p < 0.001), significant anticholinergic burden (ACB OR 3.433 (1.746–6.750), p < 0.001, CALS OR 2.166 (1.157–4.055), p = 0.016) disease severity in the Hoehn-Yahr scale (ACB OR 1.752 (1.197–2.565), p = 0.004, CALS OR 1.831 (1.256–2.670), p = 0.002) and atrial fibrillation (ACB OR 5.593 (1.417–22.083), p = 0.014, CALS OR 5.159 (1.314–20.254), p = 0.016). Conclusions and clinical implications. The anticholinergic burden is larger in PDD patients compared to PD patients without dementia. CALS or ACB scales are helpful in this risk assessment and might be crucial to avoid the development of PDD, especially in older PD patients with multimorbidities

Psychometric properties of the Polish adaptation of short form of the Empathy Quotient (EQ-Short)

Aim. The purpose of the present study was to analyze the psychometric properties of the Polish-language version of the EQ-Short questionnaire, designed to measure affective and cognitive empathy. Method. 940 subjects, aged 15-80, took part in the study. Subjects fluent in both Polish and English (N = 31) completed the questionnaire in the original English version and its Polish translation. The remaining subjects (N = 909) participated in a study designed to verify construct validity and reliability of the Polish version of the tool. Results. The Polish and English versions of the EQ-Short show linguistic equivalence at a satisfactory level (r = 0.80, p < 0.001). Tests of validity and reliability of the translated tool showed that the Polish-language EQ-Short has good psychometric properties (Cronbach’s α = 0.78), comparable to the original version. In all age groups there were statistically significant sex differences in EQ-Short scores: women scored higher than men. Conclusion. The Polish-language adaptation of EQ-Short is linguistically and psychometrically similar to the English original and meets the criteria of a reliable tool for measuring empathy

Development and characterization of phospho-ubiquitin antibodies to monitor PINK1-PRKN signaling in cells and tissue

The selective removal of dysfunctional mitochondria, a process termed mitophagy, is critical for cellular health and impairments have been linked to aging, Parkinson disease, and other neurodegenerative conditions. A central mitophagy pathway is orchestrated by the ubiquitin (Ub) kinase PINK1 together with the E3 Ub ligase PRKN/Parkin. The decoration of damaged mitochondrial domains with phosphorylated Ub (p-S65-Ub) mediates their elimination though the autophagy system. As such p-S65-Ub has emerged as a highly specific and quantitative marker of mitochondrial damage with significant disease relevance. Existing p-S65-Ub antibodies have been successfully employed as research tools in a range of applications including western blot, immunocytochemistry, immunohistochemistry, and enzyme-linked immunosorbent assay. However, physiological levels of p-S65-Ub in the absence of exogenous stress are very low, therefore difficult to detect and require reliable and ultrasensitive methods. Here we generated and characterized a collection of novel recombinant, rabbit monoclonal p-S65-Ub antibodies with high specificity and affinity in certain applications that allow the field to better understand the molecular mechanisms and disease relevance of PINK1-PRKN signaling. These antibodies may also serve as novel diagnostic or prognostic tools to monitor mitochondrial damage in various clinical and pathological specimens. Abbreviations: AD: Alzheimer disease; CCCP: carbonyl cyanide 3-chlorophenylhydrazone; ELISA: enzyme-linked immunosorbent assay; HEK293E cell: human embryonic kidney E cell; ICC: immunocytochemistry; IHC: immunohistochemistry: KO: knockout; LoB: limit of blank; LoD: limit of detection; LoQ: limit of quantification; MEF: mouse embryonic fibroblast; MSD: Meso Scale Discovery; n.s.: non-significant; nonTg: non-transgenic; PBMC: peripheral blood mononuclear cell; PD: Parkinson disease; p-S65-PRKN: phosphorylated PRKN at serine 65; p-S65-Ub: phosphorylated Ub at serine 65; Ub: ubiquitin; WT: wild-type.</p

A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer's disease risk and increased TREML1 and TREM2 brain gene expression

Introduction: We hypothesized that common Alzheimer's disease (AD)-associated variants within the triggering receptor expressed on myeloid (TREM) gene cluster influence disease through gene expression. Methods: Expression microarrays on temporal cortex and cerebellum from ∼400 neuropathologically diagnosed subjects and two independent RNAseq replication cohorts were used for expression quantitative trait locus analysis. Results: A variant within a DNase hypersensitive site 5′ of TREM2, rs9357347-C, associates with reduced AD risk and increased TREML1 and TREM2 levels (uncorrected P = 6.3 × 10−3 and 4.6 × 10−2, respectively). Meta-analysis on expression quantitative trait locus results from three independent data sets (n = 1006) confirmed these associations (uncorrected P = 3.4 × 10−2 and 3.5 × 10−3, Bonferroni-corrected P = 6.7 × 10−2 and 7.1 × 10−3, respectively). Discussion: Our findings point to rs9357347 as a functional regulatory variant that contributes to a protective effect observed at the TREM locus in the International Genomics of Alzheimer's Project genome-wide association study meta-analysis and suggest concomitant increase in TREML1 and TREM2 brain levels as a potential mechanism for protection from AD