87 research outputs found
Bench-to-bedside review: Inhaled nitric oxide therapy in adults
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Machado-Joseph disease in a Sudanese family links East Africa to Portuguese families and allows reestimation of ancestral age of the Machado lineage
No full textMachado-Joseph disease (MJD/SCA3) is the most frequent dominant ataxia worldwide. It is caused by a (CAG)n expansion. MJD has two major ancestral backgrounds: the Machado lineage, found mainly in Portuguese families; and the Joseph lineage, present in all five continents, probably originating in Asia. MJD has been described in a few African and African-American families, but here we report the first diagnosed in Sudan to our knowledge. The proband presented with gait ataxia at age 24; followed by muscle cramps and spasticity, and dysarthria, by age 26; he was wheel-chair bound at 29 years of age. His brother had gait problems from age 20 years and, by age 21, lost the ability to run, showed dysarthria and muscle cramps. To assess the mutational origin of this family, we genotyped 30 SNPs and 7 STRs flanking the ATXN3_CAG repeat in three siblings and the non-transmitting father. We compared the MJD haplotype segregating in the family with our cohort of MJD families from diverse populations. Unlike all other known families of African origin, the Machado lineage was observed in Sudan, being shared with 86 Portuguese, 2 Spanish and 2 North-American families. The STR-based haplotype of Sudanese patients, however, was distinct, being four steps (2 STR mutations and 2 recombinations) away from the founder haplotype shared by 47 families, all of Portuguese extraction. Based on the phylogenetic network constructed with all MJD families of the Machado lineage, we estimated a common ancestry at 3211 ± 693 years ago. © 2023, The Author(s)
Prevalence of repeat expansions causing autosomal dominant spinocerebellar ataxias in Hokkaido, the northernmost island of Japan
No full textIn Japan, approximately 30% of spinocerebellar degeneration (SCD) is hereditary, and more than 90% of hereditary SCD is autosomal dominant SCD (AD-SCD). We have previously reported the types of AD-SCD in Hokkaido, twice. In this study, we investigated the status of AD-SCD mainly due to repeat expansions, covering the period since the last report. We performed genetic analysis for 312 patients with a clinical diagnosis of SCD, except for multiple system atrophy at medical institutions in Hokkaido between January 2007 and December 2020. The median age at the time of analysis was 58 (1-86) years. Pathogenic variants causing AD-SCD due to repeat expansion were found in 61.5% (192 cases). Spinocerebellar ataxia (SCA) 6 was the most common type in 25.3% (79 cases), followed by Machado-Joseph disease (MJD)/SCA3 in 13.8% (43), SCA1 in 6.4% (20), SCA2 in 5.1% (16), SCA31 in 4.8% (15), dentatorubral-pallidoluysian atrophy in 4.8% (15), SCA7 in 0.6% (2), and SCA8 in 0.6% (2). SCA17, 27B, 36, and 37 were not found. Compared to previous reports, this study found a higher prevalence of SCA6 and a lower prevalence of MJD/SCA3. An increasing number of cases identified by genetic testing, including cases with no apparent family history, accurately revealed the distribution of disease types in Hokkaido
Evidence for profile changes in PSR J1713+0747 using the uGMRT
No full textPSR J1713+0747 is one of the most precisely timed pulsars in the international pulsar timing array experiment. This pulsar showed an abrupt profile shape change between 2021 April 16, (MJD 59320) and 2021 April 17 (MJD 59321). In this paper, we report the results from multi-frequency observations of this pulsar carried out with the upgraded Giant Metrewave Radio Telescope (uGMRT) before and after the event. We demonstrate the profile change seen in Band 5 (1260 MHz-1460 MHz) and Band 3 (300 MHz-500 MHz). The timing analysis of this pulsar shows a disturbance accompanying this profile change followed by a recovery with a time-scale of ∼159 days. Our data suggest that a model with chromatic index as a free parameter is preferred over models with combinations of achromaticity with DM bump or scattering bump. We determine the frequency dependence to be ∼ν+1.34. © 2021 The Author(s) Published by Oxford University Press on behalf of Royal Astronomical Society
Evidence for profile changes in PSR J1713+0747 using the uGMRT
No full textPSR J1713+0747 is one of the most precisely timed pulsars in the international pulsar timing array experiment. This pulsar showed an abrupt profile shape change between 2021 April 16, (MJD 59320) and 2021 April 17 (MJD 59321). In this paper, we report the results from multi-frequency observations of this pulsar carried out with the upgraded Giant Metrewave Radio Telescope (uGMRT) before and after the event. We demonstrate the profile change seen in Band 5 (1260 MHz-1460 MHz) and Band 3 (300 MHz-500 MHz). The timing analysis of this pulsar shows a disturbance accompanying this profile change followed by a recovery with a time-scale of ∼159 days. Our data suggest that a model with chromatic index as a free parameter is preferred over models with combinations of achromaticity with DM bump or scattering bump. We determine the frequency dependence to be ∼ν+1.34. © 2021 The Author(s) Published by Oxford University Press on behalf of Royal Astronomical Society
P45 Mechanisms of regeneration: retinoic acid acts via the endothelium to drive human lung repair
No full textMutagenicity of particle emissions from solid fuel cookstoves: A literature review and research perspective
No full textHousehold solid fuel use is a major source of many air pollutants causing severe air pollution and adverse health outcomes. In evaluation of health impacts of household air pollution, it is essential to characterize toxic properties like mutagenicity of residential fuel combustion emissions and exposure assessments. Mutagenicity of emissions from solid fuel cookstoves were analyzed through a literature review. T98 and TA100 strains are two most widely used strains in mutagenic Ames test, and results for these two strains are generally positively correlated though they have different endpoints. Direct and indirect mutagenic activities are positively correlated, and statistically insignificantly different though indirect mutagenic emissions are apparently higher. Mutagenicity emission factors on the basis of fuel energy (MJ) or useful energy delivered (MJd) for solid fuel cookstoves vary in nearly 3 orders of magnitude, ranging from 3.0 x 10(4) rev./MJd to 1.8 x 10(7) rev./MJd (or 1.1 x 10(4) rev./MJ to 4.2 x 10(6) rev./MJ). Low mutagenic emissions are reported for high efficiency stoves such as a forced-draft one. Mutagenicity emission factors are positively correlated with emissions of PM2.5. Relationship between mutagenicity and polycyclic aromatic hydrocarbons (PAHs) emissions is inconsistent among studies as PAHs are minor fractions of toxic organics contributing to the total mutagenicity. Generally, studies on mutagenicity of emissions from household cookstoves are very limited, and future studies are encouraged on mutagenic emissions from different fuel types and household stoves, evaluation of mutagenic activities of both gaseous and particulate emissions, and toxicology and exposure assessments of household air pollution.SCI(E)REVIEW761-76915
Dermatology
No full textDermatology continues to develop at a steady pace. In the past few years there have been exciting advances in our understanding of skin structure and function in health and disease and progress in genetics, epidemiology, immunology, pharmacology and clinical dermatology that have led to new approaches for managing skin diseases. This article will discuss a number of recent advances including treatments that have entered clinical practice recently or are likely to do so soon and have an impact on dermatological practice in years to come. Issues likely to be of interest to a general medical audience are emphasised.peer-reviewe
Embodied skillful performance: where the action is
No full text© 2021, The Author(s). When someone masters a skill, their performance looks to us like second nature: it looks as if their actions are smoothly performed without explicit, knowledge-driven, online monitoring of their performance. Contemporary computational models in motor control theory, however, are instructionist: that is, they cast skillful performance as a knowledge-driven process. Optimal motor control theory (OMCT), as representative par excellence of such approaches, casts skillful performance as an instruction, instantiated in the brain, that needs to be executed—a motor command. This paper aims to show the limitations of such instructionist approaches to skillful performance. We specifically address the question of whether the assumption of control-theoretic models is warranted. The first section of this paper examines the instructionist assumption, according to which skillful performance consists of the execution of theoretical instructions harnessed in motor representations. The second and third sections characterize the implementation of motor representations as motor commands, with a special focus on formulations from OMCT. The final sections of this paper examine predictive coding and active inference—behavioral modeling frameworks that descend, but are distinct, from OMCT—and argue that the instructionist, control-theoretic assumptions are ill-motivated in light of new developments in active inference
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