Validation of the Polish version of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS)

Background. In 2008, the Movement Disorders Society (MDS) published a new Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) as the official benchmark scale for Parkinson’s Disease (PD). We have translated and validated the Polish version of the MDS-UPDRS, explored its dimensionality, and compared it to the original English one. Methods. The MDS-UPDRS was translated into Polish by a team of Polish investigators led by JS and GO. The back-translation was completed by colleagues fluent in both languages (Polish and English) who were not involved in the original translation, and was reviewed by members of the MDS Rating Scales Programme. Then the translated version of the MDS-UPDRS underwent cognitive pretesting, and the translation was modified based on the results. The final translation was approved as the Official Working Document of the MDS-UPDRS Polish version, and was tested on 355 Polish PD patients recruited at movement disorders centres all over Poland (at Katowice, Gdańsk, Łódź, Warsaw, Wrocław, and Kraków). Confirmatory and explanatory factor analyses were applied to determine whether the factor structure of the English version could be confirmed in the Polish version. Results. The Polish version of the MDS-UPDRS showed satisfactory clinimetric properties. The internal consistency of the Polish version was satisfactory. In the confirmatory factor analysis, all four parts had greater than 0.90 comparative fit index (CFI) compared to the original English MDS-UPDRS. Explanatory factor analysis suggested that the Polish version differed from the English version only within an acceptable range. Conclusions and clinical implications. The Polish version of the MDS-UPDRS meets the requirements to be designated as the Official Polish Version of the MDS-UPDRS, and is available on the MDS web page. We strongly recommend using the MDS-UPDRS instead of the UPDRS for research purposes and in everyday clinical practice.

Mechanical thrombectomy in acute stroke – Five years of experience in Poland

Objectives Mechanical thrombectomy (MT) is not reimbursed by the Polish public health system. We present a description of 5 years of experience with MT in acute stroke in Comprehensive Stroke Centers (CSCs) in Poland. Methods and results We retrospectively analyzed the results of a structured questionnaire from 23 out of 25 identified CSCs and 22 data sets that include 61 clinical, radiological and outcome measures. Results Most of the CSCs (74%) were founded at University Hospitals and most (65.2%) work round the clock. In 78.3% of them, the working teams are composed of neurologists and neuro-radiologists. All CSCs perform CT and angio-CT before MT. In total 586 patients were subjected to MT and data from 531 of them were analyzed. Mean time laps from stroke onset to groin puncture was 250±99min. 90.3% of the studied patients had MT within 6h from stroke onset; 59.3% of them were treated with IV rt-PA prior to MT; 15.1% had IA rt-PA during MT and 4.7% – emergent stenting of a large vessel. M1 of MCA was occluded in 47.8% of cases. The Solitaire device was used in 53% of cases. Successful recanalization (TICI2b–TICI3) was achieved in 64.6% of cases and 53.4% of patients did not experience hemorrhagic transformation. Clinical improvement on discharge was noticed in 53.7% of cases, futile recanalization – in 30.7%, mRS of 0–2 – in 31.4% and mRS of 6 in 22% of cases. Conclusion Our results can help harmonize standards for MT in Poland according to international guidelines

Biotherapeutic potential of RNAi technology

W ciągu ostatnich lat zjawisko interferencji RNA (RNAi) stało się powszechnie wykorzystywane jako eksperymentalne narządzie do analizy genów oraz pełnionych przez nie funkcji. Wraz ze wzrostem wiedzy na temat molekularnych mechanizmów działania endogennego interferującego RNA, małe interferujące RNA (siRNA), mogą pojawić się jako grupa innowacyjnych bioleków stosowanych do leczenia wielu chorób m.in. chorób nowotworowych. Poznanie i zrozumienie szlaków molekularnych istotnych w procesie nowotworzenia stwarza możliwości dla terapii nowotworowej wykorzystującej mechanizm RNAi. Nowe terapie w leczeniu nowotworów są niezbędne, a wykorzystanie małych interferujących RNA może stanowić realną strategię.In the last few years, RNA interference (RNAi) has become widely used as an experimental tool for the analyses of genes and their functions. With increasing knowledge about the molecular mechanisms of function of endogenous RNA interference, small interfering RNA (siRNA), may occur as innovative bio-drugs for treatment of diseases such as cancer. Knowledge and understanding of the molecular pathways important for carcinogenesis create opportunities for cancer therapy using RNAi mechanism. New therapies are essential for tumors treatment, and small interfering RNAs may provide a viable strategy

Long-term changes in ovarian follicles of gilts exposed neonatally to methoxychlor : effects on oocyte-derived factors, anti-Müllerian hormone, follicle-stimulating hormone, and cognate receptors

In this paper, we investigated the effects of neonatal exposure to methoxychlor (MXC), a synthetic organochlorine used as an insecticide with estrogenic, antiestrogenic, and antiandrogenic activities on ovarian follicles of adult pigs. Piglets were injected with MXC (20 μg/kg body weight) or corn oil (controls) from postnatal Day 1 to Day 10 (n = 5 per group). Then, mRNA expression, protein abundance and immunolocalization of growth and differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15), anti-Müllerian hormone (AMH) and cognate receptors (ACVR1, BMPR1A, BMPR1B, TGFBR1, BMPR2, and AMHR2), as well as FSH receptor (FSHR) were examined in preantral and small antral ovarian follicles of sexually mature gilts. The plasma AMH and FSH levels were also assessed. In preantral follicles, neonatal exposure to MXC increased GDF9, BMPR1B, TGFBR1, and BMPR2 mRNAs, while the levels of AMH and BMP15 mRNAs decreased. In addition, MXC also decreased BMP15 and BMPR1B protein abundance. Regarding small antral follicles, neonatal exposure to MXC upregulated mRNAs for BMPR1B, BMPR2, and AMHR2 and downregulated mRNAs for AMH, BMPR1A, and FSHR. MXC decreased the protein abundance of AMH, and all examined receptors in small antral follicles. GDF9 and BMP15 were immunolocalized in oocytes and granulosa cells of preantral follicles of control and treated ovaries. All analyzed receptors were detected in the oocytes and granulosa cells of preantral follicles, and in the granulosa and theca cells of small antral follicles. The exception, however, was FSHR, which was detected only in the granulosa cells of small antral follicles. In addition, MXC decreased the plasma AMH and FSH concentrations. In conclusion, the present study may indicate long-term effects of neonatal MXC exposure on GDF9, BMP15, AMH, and FSH signaling in ovaries of adult pigs. However, the MXC effects varied at different stages of follicular development. It seems that neonatal MXC exposure may result in accelerated initial recruitment of ovarian follicles and impaired cyclic recruitment of antral follicles

The influence of estradiol and progesterone on the concentrations of uterine oxytocin receptors and plasma PGFM in response to oxytocin in ovariectomized gilts

Peripubertal gilts ($n = 25$) were treated with corn oil (CO) or ovarian steroids, one month following an ovariectomy. The first day of treatment was assigned as the first day of the experiment. The gilts received: Group (Gr) I ($n = 4$) – CO (2 ml$\cdot$day$^{-1}$ from 1st to 12th day), Gr II ($n = 4$) and Gr III ($n = 4$) – progesterone (P$_4$; 10 to 100 mg$\cdot$day$^{-1}$ from 1st to 12th day), Gr IV ($n = 5$) – estradiol benzoate (EB; 400 $\mu$g$\cdot$day$^{-1}$ from 1st to 3rd day), Gr V ($n = 4$) and Gr VI ($n = 4$) – EB + P$_4$ (EB 400 $\mu$g$\cdot$day$^{-1}$ from 1st to 3rd day, 20 $\mu$g$\cdot$day$^{-1}$ at 6th and 9th day, 50 $\mu$g at 12th day plus P$_4$ 10 to 100 mg from 4th to 15th day). All gilts were injected with oxytocin (OT; 20 IU; i.v.) on the following days of the experiment: 13th (Gr I and Gr II), 15th (Gr III and Gr IV), 16th (Gr V) and 18th (Gr VI). Concentrations of the PGF$_{2\alpha}$ metabolite – PGFM were determined in blood samples, collected from 30 min before to 120 min after OT injection. Baseline PGFM concentrations (30 min before OT) differed among treatment groups and were the highest in Gr V and Gr VI ($P < 0.01$ vs. other groups). The magnitude of the PGFM response to OT increased only in four of the five gilts of Gr IV and in three of the four gilts of Gr VI, and it was higher ($P = 0.009$) in Gr VI than in Gr IV. In the remaining groups, PGFM concentrations did not increase above the baseline in response to OT. The day after OT injection, oxytocin receptors (OTR) were found in the uterine tissues of all animals studied. The lowest OTR concentrations were in Gr I – 75.5 $\pm$ 11.2 fmol$\cdot$mg protein$^{-1}$ and the highest in Gr IV – 712.9 $\pm$ 86.7 fmol$\cdot$mg protein$^{-1}$; ($P < 0.05$ vs. other groups). The values of K$_{\rm d}$ of OTR differed among groups ($P < 0.001$) and ranged from 1.62 $\pm$ 0.44 nM in Gr I to 12. 08 $\pm$ 1.9 nM in Gr VI. A positive correlation ($r = 0.54$; $P < 0.01$) between plasma E$_2$ and uterine OTR concentrations was observed. In conclusion, E$_2$ and P$_4$ are involved in both PGF$_{2\alpha}$ synthesis/secretion and OTR formation, however, full PGF$_{2\alpha}$ response to OT does not develop before puberty. Estrogens are evident stimulators of uterine OTR synthesis in gilts

Focus on the Role of Klotho Protein in Neuro-Immune Interactions in HT-22 Cells Upon LPS Stimulation

Neuroinflammation is defined as the activation of the brain&rsquo;s innate immune system in response to an inflammatory challenge and is considered to be a prominent feature of neurodegenerative diseases. The contribution of overactivated neuroglial cells to neuroinflammation and neurodegenerative disorders is well documented, however, the role of hippocampal neurons in the neuroinflammatory process remains fragmentary. In this study, we show for the first time, that klotho acts as a signal transducer between pro-survival and pro-apoptotic crosstalk mediated by ER stress in HT-22 hippocampal neuronal cells during LPS challenge. In control HT-22 cells, LPS treatment results in activation of the IRE1&alpha;-p38 MAPK pathway leading to increased secretion of anti-inflammatory IL-10, and thus, providing adaptation mechanism. On the other hand, in klotho-deficient HT-22 cells, LPS induces oxi-nitrosative stress and genomic instability associated with telomere dysfunctions leading to p53/p21-mediated cell cycle arrest and, in consequence, to ER stress, inflammation as well as of apoptotic cell death. Therefore, these results indicate that klotho serves as a part of the cellular defense mechanism engaged in the protection of neuronal cells against LPS-mediated neuroinflammation, emerging issues linked with neurodegenerative disorders