Spinocerebellar ataxia types 1, 2, 3, and 6: disease severity and nonataxia symptoms.

OBJECTIVE: To identify factors that determine disease severity and clinical phenotype of the most common spinocerebellar ataxias (SCAs), we studied 526 patients with SCA1, SCA2, SCA3. or SCA6. METHODS: To measure the severity of ataxia we used the Scale for the Assessment and Rating of Ataxia (SARA). In addition, nonataxia symptoms were assessed with the Inventory of Non-Ataxia Symptoms (INAS). The INAS count denotes the number of nonataxia symptoms in each patient. RESULTS: An analysis of covariance with SARA score as dependent variable and repeat lengths of the expanded and normal allele, age at onset, and disease duration as independent variables led to multivariate models that explained 60.4% of the SARA score variance in SCA1, 45.4% in SCA2, 46.8% in SCA3, and 33.7% in SCA6. In SCA1, SCA2, and SCA3, SARA was mainly determined by repeat length of the expanded allele, age at onset, and disease duration. The only factors determining the SARA score in SCA6 were age at onset and disease duration. The INAS count was 5.0 +/- 2.3 in SCA1, 4.6 +/- 2.2 in SCA2, 5.2 +/- 2.5 in SCA3, and 2.0 +/- 1.7 in SCA6. In SCA1, SCA2, and SCA3, SARA score and disease duration were the strongest predictors of the INAS count. In SCA6, only age at onset and disease duration had an effect on the INAS count. CONCLUSIONS: Our study suggests that spinocerebellar ataxia (SCA) 1, SCA2, and SCA3 share a number of common biologic properties, whereas SCA6 is distinct in that its phenotype is more determined by age than by disease-related factors

The personal experience of parenting a child with Juvenile Huntington’s Disease: perceptions across Europe

The study reported here presents a detailed description of what it is like to parent a child with juvenile Huntington’s disease in families across four European countries. Its primary aim was to develop and extend findings from a previous UK study. The study recruited parents from four European countries: Holland, Italy, Poland and Sweden,. A secondary aim was to see the extent to which the findings from the UK study were repeated across Europe and the degree of commonality or divergence across the different countries. Fourteen parents who were the primary caregiver took part in a semistructured interview. These were analyzed using an established qualitative methodology, interpretative phenomenological analysis. Five analytic themes were derived from the analysis: the early signs of something wrong; parental understanding of juvenile Huntington’s disease; living with the disease; other people’s knowledge and understanding; and need for support. These are discussed in light of the considerable convergence between the experiences of families in the United Kingdom and elsewhere in Europe

Early symptoms in spinocerebellar ataxia type 1, 2, 3, and 6.

Abstract: Onset of genetically determined neurodegenerative diseases is difficult to specify because of their insidious and slowly progressive nature. This is especially true for spinocerebellar ataxia (SCA) because of varying affection of many parts of the nervous system and huge variability of symptoms. We investigated early symptoms in 287 patients with SCA1, SCA2, SCA3, or SCA6 and calculated the influence of CAG repeat length on age of onset depending on (1) the definition of disease onset, (2) people defining onset, and (3) duration of symptoms. Gait difficulty was the initial symptom in two-thirds of patients. Double vision, dysarthria, impaired hand writing, and episodic vertigo preceded ataxia in 4% of patients, respectively. Frequency of other early symptoms did not differ from controls and was regarded unspecific. Data about disease onset varied between patients and relatives for 1 year or more in 44% of cases. Influence of repeat length on age of onset was maximum when onset was defined as beginning of permanent gait disturbance and cases with symptoms for more than 10 years were excluded. Under these conditions, CAG repeat length determined 64% of onset variability in SCA1, 67% in SCA2, 46% in SCA3, and 41% in SCA6 demonstrating substantial influence of nonrepeat factors on disease onset in all SCA subtypes. Identification of these factors is of interest as potential targets for disease modifying compounds. In this respect, recognition of early symptoms that develop before onset of ataxia is mandatory to determine the shift from presymptomatic to affected status in SCA

Interest in abandoned cultural heritage. Motives for traveling to the chernobyl zone hidden behind the facade of official statistics

W opracowaniu poświęcono uwagę jądrowej spuściźnie Ukrainy i Białorusi, jakim jest strefa czarnobylska. Po ponad trzydziestu latach od katastrofy w czarnobylskiej elektrowni, pozostającej w sąsiedztwie Czarnobyla i Prypeci, można zauważyć stale rosnące wskaźniki odwiedzin tych miejsc. Wzrastająca ruchliwość podróżników na tym terenie utwierdza w przekonaniu, że na opuszczone dziedzictwo kulturowe jest popyt, a dodatkowym kamieniem milowym był sukces serialu emitowanego przez stację telewizyjną HBO o tytule: Czarnobyl. W tekście autor przedstawia motywy osób się tam udających, wykorzystując informacje pozyskane w rozmowach z podróżnikami. Treść opracowania wsparta jest zdjęciami, które pokazują strefę czarnobylską przed wypadkiem i po ponad trzydziestu latach (obecnie). Prezentowany tekst jest wynikiem analizy oficjalnych statystyk pozyskanych z oficjalnych witryn internetowych organizacji zarządzających strefą czarnobylską, odwiedzin oraz badań etnograficznych autora, które prowadzone były przy okazji osobistych kontaktów z podróżnikami, podczas wyjazdów do tych miejsc.The study focuses on the nuclear legacy of Ukraine and Belarus, the Chernobyl zone. More than thirty years after the disaster at the Chernobyl power plant, re maining in the vicinity of Chernobyl and Pripyat, you can see ever increasing rates of site visits. The increasing mobility of travellers in this area confirms the belief that the abandoned cultural heritage is in demand, and an additional milestone was the success of the series broadcast by the HBO television station Chernobyl. In the text I present motives of people going there, using information obtained in conversations with travellers. The content of the study is supported by photos that show the Chernobyl zone before the accident and over thirty years after (now). The text should be treated as the results of analyzes of official statistics obtained from official websites of organizations managing the Chernobyl zone of visits and my ethnographic research, which are conducted on the occasion of personal contacts with travellers during trips to this place.Uniwersytet w BiałymstokuAndrzej Strupczewski: skutki awarii w Czarnobylu nie są pomijalne, ale są małe, (2017), licznikgeigera.pl/andrzej­‑strupczewski-skutki­‑awarii-w-czarnobylunie-sa­‑pomijalne-ale­‑sa-male/, [dostęp: 15 grudnia 2019].Banaszkiewicz M., (2018), Turystyka w miejscach kłopotliwego dziedzictwa, Kraków, Wydawnictwo Uniwersytetu Jagiellońskiego.Czarnobyl Wiki, czarnobyl.wikia.com, [dostęp: 10 grudnia 2019].Konecki K., (2000), Studia z metodologii badań jakościowych. Teoria Ugruntowana, Warszawa, Wydawnictwo Naukowe PWN.Mysterious Red Forest of Chernobyl area, (2016), https://chernobylguide.com/red_forest/, [dostęp: 1 grudnia 2019].Nieszczerzewska M., (2016), Miejska eksploracja. Aktywacja bez interwencji?, „Kultura i Historia”, nr 30.Novyny, https://cotiz.org.ua/novyny, [dostęp: 12 grudnia 2019].Pripyat­‑city, https://pripyat‑city.ru, [dostęp: 15 grudnia 2019].Rakowicz P., (2019), Etnografia terenowa w opuszczonych aglomeracjach północnej Ukrainy. Uwarunkowania wyjazdu do strefy czarnobylskiej na gruncie socjologii jakościowej, [w:] Oblicza dużego miasta: instytucje, organizacje, procesy, B. Cieślińska (red.), Białystok, Wydawnictwo Uniwersytetu w Białymstoku.Trzęsicki K., (2018), Wprowadzenie do metodologii nauk społecznych, Białystok, Wydawnictwo Uniwersytetu w Białymstoku.Znaniecki F., (1992), Nauki o kulturze, Warszawa, Wydawnictwo Naukowe PWN.22924

Etnografia terenowa w opuszczonych aglomeracjach północnej Ukrainy. Uwarunkowania wyjazdu do strefy czarnobylskiej na gruncie socjologii jakościowej

Angrosino Michael. 2015. Badania etnograficzne i obserwacyjne. Przeł. M. Brzozowska-Brywczyńska. Warszawa: PWN.Aronson Elliot. 1995. Człowiek Istota Społeczna. Przeł. J. Radzicki. Warszawa: PWN.Banaszkiewicz Magdalena. 2018. Turystyka w miejscach kłopotliwego dziedzictwa. Kraków: Wydawnictwo Uniwersytetu Jagiellońskiego.Berger Peter, Luckmann Thomas. 1983. Społeczne tworzenie rzeczywistości. Warszawa: PIW.Geertz Clifford. 2005. Interpretacja kultur. Wybrane eseje. Przeł. Piechaczek M. M. Kraków: Wydawnictwo Uniwersytetu JagiellońskiegoHensel Przemysław, Glinka Beata. 2012. Teoria ugruntowana. W: Jemielniak D. (red.). Badania jakościowe. Podejścia i teorie, tom 1, Warszawa: PWN: 89-113.Konecki Krzysztof. 2000. Studia z Metodologii Badań Jakościowych: Teoria Ugruntowana. Warszawa: PWN.Ochitowicz Michaił. 1930. „Zamietki po teorii rassienija”, Sowremiennaja Architiektura, za: B. Jałowiecki, M. Szczepański .2006. „Miasto i Przestrzeń w perspektywie socjologicznej”. Warszawa: Scholar.Podemski Krzysztof. 2004. Socjologia podróży. Poznań: Wydawnictwo Naukowe Uniwersytetu im. Adama Mickiewicza w Poznaniu.Pokojska Weronika. 2015. Zapomniane dziedzictwo, czyli Urban Exploring. „Zarządzanie w Kulturze”, 16 (2): 151-163.Rakowicz Piotr. 2017. Tanatoturystyka – niekonwencjonalne wycieczki do opuszczonego miasta Prypeć. Perspektywa socjologiczna. „Miscellanea Anthropologica et Sociologica”, 18 (2): 207-219.Rakowicz Piotr. 2018. Wycieczki do Prypeci i Czarnobyla jako przykład tanatoturystyki. W: Nieroba E., Kopczak – Wirga A. (red. nauk.) Sztuka podróżowania, czyli turysta w świecie kultury, Opole: Wydawnictwo Uniwersytetu Opolskiego: 131-144.Rakowicz Piotr. 2018. Skażone pogranicze Ukrainy i Białorusi w „Chernobyl VR Project”. Próba analizy zjawiska wirtualnej turystyki. W: Culturogical Almanac, Issue 10, Vinnytsia: TVORY: 69-78.Seaton Anthony V. 1996. From Thanatopsis to Thanatourism. Guided by the Dark. „International Journal of Heritage Studies”, 2 (4): 234-244.Strelau Jan. 2014. Psychologia – podręcznik akademicki. Tom 2, Gdańsk: GWPSzacka Barbara. 2003. Wprowadzenie do socjologii. Warszawa: Oficyna Naukowa.Tajfel Henri. 1972. Social Categorization. English MS of La Categorization Social. W: Moscovici S. (red.) Introduction a la psychologie sociale, t. 1, Paris: Larousse.Tanaś Sławoj. 2013. Tanatoturystyka: od przestrzeni śmierci do przestrzeni turystycznej. Łódź: Wydawnictwo Uniwersytetu Łódzkiego.Turner John C. 1982. Towards a Cognitive Redefi nition of the Social Group. W: Tajfel H. (red.) Social Identity and Intergroup Relations, Cambridge: 15-40.alienatours.pl/sylwester_prypec_1985_powrot_do_przeszlosci.php (dostęp 20.03.2019).dazv.gov.ua/en/news-and-media/vitalii-petruk-in-order-to-improve-the-quality-of-service-of-visitors-to-the-exclusion-zone-it-is-necessary-to-adhere-in-cooperation-with-companies-to-all-the-legislative-principles-of-competition.html (dostęp: 26.04.2018).cotiz.org.ua (dostęp: 10.07.2019).nuclear.pl/wiadomosci,news,19012101,0,0.html (dostęp: 20.03.2019).https://www.imdb.com/title/tt7366338/?ref_=fn_al_tt_1 (dostęp: 10.07.2019).14316

Novel Family of Gynecologic Cancer Antigens Detected by Anti-HIV Antibody

Objective: The reactivity of gynecologic cancer proteins with monoclonal antibody (MAb) directed against the human immunodeficiency virus I (HIV-I) was tested

High relative frequency of SCA1 in Poland reflecting a potential founder effect

Spinocerebellar ataxias (SCAs) have irregular distributions worldwide. SCA1 is the most frequent in Poland, and no cases of SCA3 of Polish origin has yet been identified. In view of such patterns of SCAs occurrence, the relative frequency, geographical distribution and a possible founder effect of SCA1 were investigated. DNA samples of 134 probands with SCA1 and 228 controls were analysed. The genotyping of four markers, D6S89, D6S109, D6S274, D6S288, around the ATXN1 gene (SCA1) and sequencing of the selected variant of D6S89 were performed. The relative frequency of SCA1 was 68 %. The studied SCA1 pedigrees were irregularly distributed, with the highest concentration in Central Poland. Haplotyping revealed the association of ATXN1 gene mutation with a 197-bp variant of D6S89 marker (63 % of probands) and with a 184-bp variant of DS6274 (50.7 % of probands). Out of 61 SCA1 probands from Mazowieckie, 41 carried the same 197-bp variant. SCA1 relative frequency in Poland shows the highest value compared with the data from other countries worldwide. Due to the association with the mutation obtained for the investigated markers and the SCA1 pedigrees concentration in Central Poland, we hypothesise that it represents a potential founder effect

Evidence for a relatively high proportion of DM2 mutations in a large group of Polish patients

Introduction: Myotonic dystrophies (DMs) type 1 (DM1) and type 2 (DM2) are autosomal dominant, multisystem disorders, considered the most common dystrophies in adults. DM1 and DM2 are caused by dynamic mutations in the DMPK and CNBP genes, respectively. Methods: Molecular analyses were performed by PCR and the modified RP-PCR in patients, in their at-risk relatives and prenatal cases. Results: The analysis of Polish controls revealed the range of 5-31 CTG repeats for DM1 and 110-228 bp alleles for DM2. Among 318 confirmed probands - 196 (62%) were DM1 and 122 (38%) – DM2. Within DM1families, 10 subjects carried a low expanded CTG tract (< 100 repeats), which resulted in a full mutation in subsequent generations. Two related individuals had unstable alleles–188 bp and 196 bp without common interruptions. Conclusion: The relative frequencies of DM1/DM2 among Polish patients were 68% and 32%, respectively, with a relatively high proportion of DM2 mutations (1.6:1)

Prediction of the age at onset in spinocerebellar ataxia type 1, 2, 3 and 6

Background: The most common spinocerebellar ataxias (SCA)—SCA1, SCA2, SCA3, and SCA6—are caused by (CAG)n repeat expansion. While the number of repeats of the coding (CAG)n expansions is correlated with the age at onset, there are no appropriate models that include both affected and preclinical carriers allowing for the prediction of age at onset. Methods: We combined data from two major European cohorts of SCA1, SCA2, SCA3, and SCA6 mutation carriers: 1187 affected individuals from the EUROSCA registry and 123 preclinical individuals from the RISCA cohort. For each SCA genotype, a regression model was fitted using a log-normal distribution for age at onset with the repeat length of the alleles as covariates. From these models, we calculated expected age at onset from birth and conditionally that this age is greater than the current age. Results: For SCA2 and SCA3 genotypes, the expanded allele was a significant predictor of age at onset (−0.105±0.005 and −0.056±0.003) while for SCA1 and SCA6 genotypes both the size of the expanded and normal alleles were significant (expanded: −0.049±0.002 and −0.090±0.009, respectively; normal: +0.013±0.005 and −0.029±0.010, respectively). According to the model, we indicated the median values (90% critical region) and the expectancy (SD) of the predicted age at onset for each SCA genotype according to the CAG repeat size and current age. Conclusions: These estimations can be valuable in clinical and research. However, results need to be confirmed in other independent cohorts and in future longitudinal studies.This study was supported by grants EUROSCA/LSHM-CT-2004-503304 from the European Union, grant from the European Community's Seventh Framework Programme (FP7/2007-2013 n° 2012-305121 NEUROMICS), GeneMove/01 GM 0503 from the German Ministry of Education and Research, within the framework of the ERA-Net for Research Programmes on Rare Diseases, grant 3 PO5B 019 24 from the Polish Ministry of Scientific Research and Information Technology, and grant No 674N—RISCA/2010—2014 from Polish Ministry of Science and Higher Education. The research leading to these results has received funding from the programme ‘Investissements d'avenir’ ANR-10-IAIHU-06. BPvdW is supported by research grants from the Netherlands Brain Foundation, the Royal Dutch Society for Physical Therapy, BBMRI-NL, and the Radboud University Medical Centre. MB is supported by the grant OTKA K 103983. AF was supported by a grant from POR CREME 2007-20013. AB was supported by the grant EUROSCA/LSHM-CT-2004-503304 and by the grant NEUROMICS (7th framework programme) from the European Union. AB, AD and GS received funding from the VERUM Foundation. AD received support from ANR (French Research Agency) and Eranet for the Risca project, PG and AC work at University College London Hospitals/University College London which receives a proportion of its funding from the Department of Health's National Institute for Health Research Biomedical Research Centres funding scheme. Paola Giunti receives funding from the EC (HEALTH-F2-2010-242193; FP7 Grant). DeNDRoN, Ataxia UK and NIHR, Department of Health

Nuclear localization and function of polypeptide ligands and their receptors: a new paradigm for hormone specificity within the mammary gland?

The specific effects triggered by polypeptide hormone/growth factor stimulation of mammary cells were considered mediated solely by receptor-associated signaling networks. A compelling body of new data, however, clearly indicates that polypeptide ligands and/or their receptors are transported into the nucleus, where they function directly to regulate the expression of specific transcription factors and gene loci. The intranuclear function of these complexes may contribute to the explicit functions associated with a given ligand, and may serve as new targets for pharmacologic intervention