Spinocerebellar ataxia type 7 (SCA7) is a human neurodegenerative polyglutamine (polyQ) disease caused by a CAG repeat expansion in the open reading frame of the ATXN7 gene. The allele-selective silencing of mutant transcripts using a repeat-targeting strategy has previously been used for several polyQ diseases. Herein, we demonstrate that the selective targeting of a repeat tract in a mutant ATXN7 transcript by RNA interference is a feasible approach and results in an efficient decrease of mutant ataxin-7 protein in patient-derived cells. Oligonucleotides (ONs) containing specific base substitutions cause the downregulation of the ATXN7 mutant allele together with the upregulation of its normal allele. The A2 ON shows high allele selectivity at a broad range of concentrations and also restores UCHL1 expression, which is downregulated in SCA7.
The response to the pandemic requires access to accurate information and public understanding and adherence to preventive measures. This online cross-sectional study of adult Poles (n = 1337) assessed the frequency of COVID-19 preventive behaviors, fears related to the COVID-19 pandemic, and beliefs in COVID-19-related conspiracy theories during the early phase of the COVID-19 pandemic when the nationwide lockdown was imposed (April 2020). As shown, 22% of surveyed admitted not to wash their hands frequently, while 12% did not use disinfectants. These two behaviors were also less frequent in individuals with medical education. The highest levels of pandemic-related fears were associated with health loss in relatives, pandemic-induced economic crisis, and government using a pandemic to control citizens by the state. A significant share of surveyed individuals believed that the pandemic was intentional action to weaken non-Chinese economies (32%) or was deliberately induced for profits from selling vaccines (27%). Men, individuals with no children, and subjects with lower education were significantly less likely to adhere to sanitary measures (handwashing, disinfection, avoiding face touching, changes in greeting etiquette, face-covering when coughing or sneezing), and were less concerned over self and relatives’ health. At the same time, men were less prone than women to the conspiracy theories related to the COVID-19 pandemic. The results indicate that adherence to sanitary measures during the pandemic can be a challenge also in developed countries, while misinformation campaigns (also concerning vaccines) have already affected the general public during the early phase of the epidemiological outbreak. The study provides observations that may be useful in the management of the public response to future epidemics.
There were worries that the COVID-19 pandemic could result in a shortage of supplies of some drugs. We aimed to analyze if the COVID-19 pandemic resulted in the availability drop of different cardiodiabetological medicaments. Special attention was put to combined therapies and to investigate the general availability of these drugs. Data were obtained from the Polish startup company GdziePoLek regarding the availability of 121 cardiodiabetolocigal drugs divided into 23 separate categories in Polish pharmacies. The period of the analysis was limited from 1 January 2019 to 31 December 2020. The threshold of a 20% decrease of median availability was set to found drugs with the most severe drop in availability during the COVID-19 pandemic. We also identified medicaments with a median availability of less than 50%. We identified two drugs with the most severe drop in availability level during COVID-19 pandemics: acenocoumarol (decrease by 52.0%) and nitrendipine (decrease by 98.3%). In 2019 and 2020, 27 of 121 drugs had a median availability lower than 50%. The limited availability concerned the most novel agents and polypills, mostly non-insulin antidiabetic drugs. The decrease in drug availability in Poland was not as severe as expected. Accessibility to some novel non-refunded medicaments is limited.
Choroba Huntingtona (HD) jest chorobą genetyczną spowodowaną przez zbyt dużą liczbę powtórzeń CAG w egzonie 1 genu HTT, kodującym huntingtynę. Od wystąpienia pierwszych symptomów choroby średnia długość życia wynosi 15-20 lat, kiedy to postępują objawy wynikające z neurodegeneracji. W związku z tym istnieje duże zapotrzebowanie na skuteczną metodę leczenia tego schorzenia. Opracowywane są strategie wykorzystujące mechanizmy wyciszenia ekspresji genów, w tym techniki edycji DNA. W tej pracy przedstawione są najważniejsze testowane obecnie podejścia, ze szczególnym uwzględnieniem strategii opierających się na wykorzystaniu oligonukleotydów antysensowych (ASO), technologii interferencji RNA (RNAi) i CRISPR-Cas9. Omówione są prowadzone obecnie próby kliniczne leczenia przyczynowego, inne najważniejsze próby terapii, a także obecnie stosowane środki farmakologiczne.
Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare, incurable genetic disease that belongs to the group of polyglutamine (polyQ) diseases. DRPLA is the most common in the Japanese population; however, its global prevalence is also increasing due to better clinical recognition. It is characterized by cerebellar ataxia, myoclonus, epilepsy, dementia, and chorea. DRPLA is caused by dynamic mutation of CAG repeat expansion in ATN1 gene encoding the atrophin-1 protein. In the cascade of molecular disturbances, the pathological form of atrophin-1 is the initial factor, which has not been precisely characterized so far. Reports indicate that DRPLA is associated with disrupted protein-protein interactions (in which an expanded polyQ tract plays a crucial role), as well as gene expression deregulation. There is a great need to design efficient therapy that would address the underlying neurodegenerative process and thus prevent or alleviate DRPLA symptoms. An in-depth understanding of the normal atrophin-1 function and mutant atrophin-1 dysfunction is crucial for this purpose.
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