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IntroductionProgressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are tauopathic atypical parkinsonisms. Given their overlap in terms of clinical manifestation, there is growing interest in the mechanisms leading to these entities.Materials and methodsIn total, 71 patients were included in the study, 19 of whom were clinically diagnosed with CBS, 37 with PSP, and 15 with Parkinson's disease (PD). The mean ages of the participants were 72.8, 72.9, and 64.0 years, respectively, and the disease duration varied from 3 to 6 years. Each individual underwent blood collection. Morphological and biochemical evaluation of blood samples was performed to analyze the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-high-density lipoprotein ratio (NHR). A single-photon emission computed tomography (SPECT) with technetium-99m hexamethylpropyleneamine oxime (99Tc-HMPAO) tracer was used to assess perfusion in two regions of interest (ROI): the thalamus and insula. Using Pearson correlation to assess the linear relationship between NHR and perfusion in the insula and thalamus for CBS, PSP, and PD patients, the authors intended to verify possible correlations between NLR, PLR, and NHR and perfusion in the indicated ROIs.ResultsThe study revealed a negative linear correlation between NHR and perfusion of both the left (Insula L; R = −0.59) and right (Insula R; R = −0.58) insula regions. Similar to the insula, a linear correlation between NHR and activity in both the left (Thalamus L) and right (Thalamus R) thalamus regions in CBS subjects with a relatively stronger correlation in the right thalamus (R = −0.64 vs. R = −0.58) was found. These observations were not confirmed in PSP and PD patients.ConclusionSimultaneously using non-specific parameters for peripheral inflammation (NLR, PLR, and NHR) and perfusion, SPECT may be an interesting beginning point for further analysis of inflammatory disease mechanisms. To the best of our knowledge, this is the first study to address the potential correlation between the peripheral neuroinflammatory markers NLR, PLR, and NHR and perfusion disturbances in particular ROIs.

Presently, there is increasing interest in rare PSP (progressive supranuclear palsy) variants, including PSP-PGF (PSP-progressive gait freezing), PSP-PI (PSP-postural instability), PSP-OM (PSP-ocular motor dysfunction), PSP-C (PSP-predominant cerebellar ataxia), PSP-CBS (PSP-corticobasal syndrome), PSP-SL (PSP-speech/language disorders), and PSP-PLS (PSP-primary lateral sclerosis). Diagnosis of these subtypes is usually based on clinical symptoms, thus thorough examination with anamnesis remains a major challenge for clinicians. The individual phenotypes often show great similarity to various neurodegenerative diseases and other genetic, autoimmune, or infectious disorders, manifesting as PSP-mimicking syndromes. At the current stage of knowledge, it is not possible to isolate a specific marker to make a definite ante-mortem diagnosis. The purpose of this review is to discuss recent developments in rare PSP phenotypes and PSP-like syndromes.

Abstract Wallachian expansion brought to the Carpathian Mountains a system of shepherd economy—farming, production of Wallachian cheeses, animals adapted to life in difficult mountain conditions—mainly sheep of the Cakiel breed group. Mountain sheep's milk is used to produce traditional cheeses: bundz, bryndza podhalańska, oscypek, redykołka—on the Polish side and Slovenská bryndza, Slovenská parenica, Slovenský oštiepok, Ovčí hrudkový syr salašnícky—on the Slovak side. Also sausages are made from sheep meat. These cheeses and sausages are salted and then traditionally smoked. The source of heat and smoke is hard wood with appropriate humidity, burned in the hearth located in the shepherd's hut, over which the cheeses are placed under the roof. Among several hundred smoke components, there are also polycyclic aromatic hydrocarbons, which, on the one hand, give the smoked product its taste and aroma, and on the other hand have carcinogenic and mutagenic properties. Sausages and cheeses from Poland and Slovakia, made from milk and meat of native sheep breeds, preserved by traditional smoking, were analyzed for polycyclic aromatic hydrocarbons content. The analyzed cheeses were characterized by a trace or low content of benzo[a]pyrene and the sum of benzo(a)pyrene, benzo(a)anthracene, benzo(b)fluoranthene and chrysene. In cheeses from outer Eastern Carpathians subprovince (Bieszczady), the high content of naphthalene, acenaphthylene, fluorene and phenanthrene is noteworthy. Polish lamb sausages were characterized by a higher content of benzo(a)pyrene and the sum of benzo(a)pyrene, benzo(a)anthracene, benzo(b)fluoranthene and chrysene. The differences result from the method of smoking (warm or cold in the south of the Carpathians—hot in the north) and the type of wood used for smoking.

Parkinson’s disease is a progressive neurodegenerative disorder, predominantly of the motor system. Although some genetic components and cellular mechanisms of Parkinson’s have been identified, much is still unknown. In recent years, emerging evidence has indicated that non-DNA-sequence variation (in particular epigenetic mechanisms) is likely to play a crucial role in the development and progression of the disease. Here, we present an up-to-date overview of epigenetic processes including DNA methylation, DNA hydroxymethylation, histone modifications and non-coding RNAs implicated in the brain of those with Parkinson’s disease. We will also discuss the limitations of current epigenetic research in Parkinson’s disease, the advantages of simultaneously studying genetics and epigenetics, and putative novel epigenetic therapies.

Rabbits are important livestock animals, popular for their nutritional value. Nowadays, the molecular background of traits influencing the quality of meat and meat products is in high demand. Therefore, in the current study, we analyse the sequences of IGFBP1, IGFBP2, IGFBP4, IGFBP5, and IGFBP6 for possible polymorphisms. Based on a bioinformatics analysis in an association study on 466 animals of different breeds (New Zealand White × Flemish Giant crossbreed (9NZWxFG), Termond White (TW), Popielno White (PW), and Flemish Giant (FG)), we analyse the influence of five polymorphisms within the IGFBP genes. Statistically significant differences were found among the carcass and meat quality traits but not for all of the analysed rabbit breeds. The most promising polymorphism was g.158093018A>T within the IGFBP5 gene. The values of pH24 of m.longissimus lumborum (m.l.l.) and biceps femoris muscles (m.b.f.) were higher for the AT genotypes compared to the AA genotypes for the TW and NZWxFG crossbreeds. Also, for pH24, we found differences in ing.41594308T>C for NZWxFG, where the TT genotype values were higher than the TC values. We found differences in L*24 on m.l.l. for g.41592248A>C for NZWxFG. For m.b.f., significant differences were found in b*45 for g.3431insAC in the FG population and a*45 for g.41592248A>C and g.158093018A>T in the TW population. The shear force statistically differed for g.158093018A>T in TW rabbits and g.41592248A>C for NZWxFG. We conclude that this polymorphism may be promising for better quality rabbit meat and may be implemented in selection processes.

Parkinson’s disease (PD) is a common movement disorder, estimated to affect 4% of individuals by the age of 80. Mutations in the glucocerebrosidase 1 (GBA1) gene represent the most common genetic risk factor for PD, with at least 7–10% of non-Ashkenazi PD individuals carrying a GBA1 mutation (PD-GBA1). Although similar to idiopathic PD, the clinical presentation of PD-GBA1 includes a slightly younger age of onset, a higher incidence of neuropsychiatric symptoms, and a tendency to earlier, more prevalent and more significant cognitive impairment. The pathophysiological mechanisms underlying PD-GBA1 are incompletely understood, but, as in idiopathic PD, α-synuclein accumulation is thought to play a key role. It has been hypothesized that this overexpression of α-synuclein is caused by epigenetic modifications. In this paper, we analyze DNA methylation levels at 17 CpG sites located within intron 1 and the promoter of the α-synuclein (SNCA) gene in three different brain regions (frontal cortex, putamen and substantia nigra) in idiopathic PD, PD-GBA1 and elderly non-PD controls. In all three brain regions we find a tendency towards a decrease in DNA methylation within an eight CpG region of intron 1 in both idiopathic PD and PD-GBA1. The trend towards a reduction in DNA methylation was more pronounced in PD-GBA1, with a significant decrease in the frontal cortex. This suggests that PD-GBA1 and idiopathic PD have distinct epigenetic profiles, and highlights the importance of separating idiopathic PD and PD-GBA1 cases. This work also provides initial evidence that different genetic subtypes might exist within PD, each characterized by its own pathological mechanism. This may have important implications for how PD is diagnosed and treated.

Parkinson disease is the most common neurodegenerative movement disorder, estimated to affect one in twenty-five individuals over the age of 80. Mutations in glucocerebrosidase 1 (GBA1) represent the most common genetic risk factor for Parkinson disease. The link between GBA1 mutations and α-synuclein accumulation, a hallmark of Parkinson disease, is not fully understood. Following our recent finding that Gba1 mutations lead to increased α-synuclein accumulation in mice, we have studied the effects of a single injection of mouse α-synuclein pre-formed fibrils into the striatum of Gba1 mice that carry a L444P knock-in mutation. We found significantly greater formation and spread of α-synuclein inclusions in Gba1-transgenic mice compared to wild-type controls. This indicates that the Gba1 L444P mutation accelerates α-synuclein pathology and spread.

Pulmonary hypertension in children with bronchopulmonary dysplasia (BPD-PH) significantly worsens the prognosis. Pulmonary vasodilators are often used in BPD-PH but the short-term outcome of treatment is not well described. The aim of this study was to evaluate BPD-PH children diagnosed beyond 36 weeks postmenstrual age treated with pulmonary vasodilators (sildenafil, bosentan, or both) and to assess the short and long-term effect of oral pulmonary vasodilators treatment. Twenty patients were included in the study. Cardiology evaluation (WHO-FC, NTproBNP, oxygen saturation, pulmonary to systemic pressure ratio PAP/SAP) was performed at diagnosis and after treatment initiation. In the majority of patients improvement in all evaluated factors was observed. No side effects of vasodilators were observed. PH resolved in 10 patients after a mean of 21.4 months of treatment. Six patients died. The number of poor prognostic factors commonly used to assess patients with pulmonary arterial hypertension (PAH) decreased significantly during BPD-PH treatment. The influence of BPD-PH perinatal risk factors on prognosis was considered but was not confirmed. In conclusion, the treatment of BPD-PH with pulmonary vasodilators was well tolerated and led to a clinical improvement with the possibility of discontinuation without recurrence of PH. Prognostic factors used in pediatric PAH risk stratification also seem to be useful in assessing treatment efficacy and prognosis in patients with BPD-PH.

The aim of this study was to investigate the molecular mechanisms leading to the identification of pathogens by congenital immune receptors in foals up to 60 days of age. The study was conducted on 16 foal Polish Pony Horses (Polish Konik) divided into two study groups: control (n = 9) and experimental (n = 7). Foals from the experimental group received an intramuscular duplicate injection of 5 mL of Biotropina (Biowet) at 35 and 40 days of age. The RNA isolated from venous blood was used to evaluate the expression of theTLR3, TLR4, and TLR7 genes using RT-PCR. The results of the experiment demonstrated a statistically significant increase in the level of TLR3 gene expression and a decrease in the level ofTLR4 gene expression with foal aging. The level of TLR7 gene expression did not show age dependence. Immunostimulation with Biotropina had a significant impact on the level of the genes’ expression for Toll-like receptors. It increased the level of TLR4 expression and decreased TLR3 expression. Thus, it was concluded that the expression of theTLR3 and TLR4genes in peripheral blood cells is dependent on age. This experiment demonstrated a strong negative correlation between TLR3 and TLR4 gene expression.