146 research outputs found
Resolution of the clinical features of tyrosinemia following orthotopic liver transplantation for hepatoma
The clinical history before transplantation and subsequent clinical and biochemical course of 3 children and one adult with hereditary tyrosinemia treated by orthotopic hepatic transplantation is described. All four patients are now free of their previous dietary restrictions and appear to be cured of both their metabolic disease and their hepatic neoplasm. © 1986 Elsevier Science Publishers B.V. All rights reserved
Molecular genetics and pathophysiology of 17 beta-hydroxysteroid dehydrogenase 3 deficiency.
Autosomal recessive mutations in the 17 beta-hydroxysteroid dehydrogenase 3 gene impair the formation of testosterone in the fetal testis and give rise to genetic males with female external genitalia. Such individuals are usually raised as females, but virilize at the time of expected puberty as the result of increases in serum testosterone. Here we describe mutations in 12 additional subjects/families with this disorder. The 14 mutations characterized to date include 10 missense mutations, 3 splice junction abnormalities, and 1 small deletion that results in a frame shift. Three of these mutations have occurred in more than 1 family. Complementary DNAs incorporating 9 of the 10 missense mutations have been constructed and expressed in reporter cells; 8 of the 9 missense mutations cause almost complete loss of enzymatic activity. In 2 subjects with loss of function, missense mutations testosterone levels in testicular venous blood were very low. Considered together, these findings strongly suggest that the common mechanism for testosterone formation in postpubertal subjects with this disorder is the conversion of circulating androstenedione to testosterone by one or more of the unaffected 17 beta-hydroxysteroid dehydrogenase isoenzymes
CYP21A2 Gene Mutations in Congenital Adrenal Hyperplasia: Genotype−phenotype correlation in Turkish children
Background: Congenital adrenal hyperplasia (CAH) due 21−hydroxylase deficiency (21−OHD) is a common autosomal recessive disorder. It is caused by defects in the CYP21A2 gene
Effects of vessel traffic on relative abundance and behaviour of cetaceans : the case of the bottlenose dolphins in the Archipelago de La Maddalena, north-western Mediterranean sea
Acknowledgements This study was part of the Tursiops Project of the Dolphin Research Centre of Caprera, La Maddalena. Financial and logistical support was provided by the Centro Turistico Studentesco (CTS) and by the National Park of the Archipelago de La Maddalena. We thank the Natural Reserve of Bocche di Bonifacio for the support provided during data collection. The authors thank the numerous volunteers of the Caprera Dolphin Research Centre and especially Marco Ferraro, Mirko Ugo, Angela Pira and Maurizio Piras whose assistance during field observation and skills as a boat driver were invaluable.Peer reviewedPostprin
The French Lexicon Project: Lexical decision data for 38,840 French words and 38,840 pseudowords
How is genetic testing evaluated? A systematic review of the literature
open8Given the rapid development of genetic tests, an assessment of their benefits, risks, and limitations is crucial for public health practice. We performed a systematic review aimed at identifying and comparing the existing evaluation frameworks for genetic tests. We searched PUBMED, SCOPUS, ISI Web of Knowledge, Google Scholar, Google, and gray literature sources for any documents describing such frameworks. We identified 29 evaluation frameworks published between 2000 and 2017, mostly based on the ACCE Framework (n = 13 models), or on the HTA process (n = 6), or both (n = 2). Others refer to the Wilson and Jungner screening criteria (n = 3) or to a mixture of different criteria (n = 5). Due to the widespread use of the ACCE Framework, the most frequently used evaluation criteria are analytic and clinical validity, clinical utility and ethical, legal and social implications. Less attention is given to the context of implementation. An economic dimension is always considered, but not in great detail. Consideration of delivery models, organizational aspects, and consumer viewpoint is often lacking. A deeper analysis of such context-related evaluation dimensions may strengthen a comprehensive evaluation of genetic tests and support the decision-making process.openPitini, Erica*; de Vito, Corrado; Marzuillo, Carolina; D’Andrea, Elvira; Rosso, Annalisa; Federici, Antonio; Di Maria, Emilio; Villari, PaoloPitini, Erica; de Vito, Corrado; Marzuillo, Carolina; D’Andrea, Elvira; Rosso, Annalisa; Federici, Antonio; Di Maria, Emilio; Villari, Paol
The organisation of physiotherapy for people with multiple sclerosis across Europe: a multicentre questionnaire survey
Background Understanding the organisational set-up of physiotherapy services across different countries is increasingly important as clinicians around the world use evidence to improve their practice. This also has to be taken into consideration when multi-centre international clinical trials are conducted. This survey aimed to systematically describe organisational aspects of physiotherapy services for people with multiple sclerosis (MS) across Europe. Methods Representatives from 72 rehabilitation facilities within 23 European countries completed an online web-based questionnaire survey between 2013 and 2014. Countries were categorised according to four European regions (defined by United Nations Statistics). Similarities and differences between regions were examined. Results Most participating centres specialized in rehabilitation (82 %) and neurology (60 %), with only 38 % specialising in MS. Of these, the Western based Specialist MS centres were predominately based on outpatient services (median MS inpatient ratio 0.14), whilst the Eastern based European services were mostly inpatient in nature (median MS inpatient ratio 0.5). In almost all participating countries, medical doctors - specialists in neurology (60 %) and in rehabilitation (64 %) - were responsible for referral to/prescription of physiotherapy. The most frequent reason for referral to/prescription of physiotherapy was the worsening of symptoms (78 % of centres). Physiotherapists were the most common members of the rehabilitation team; comprising 49 % of the team in Eastern countries compared to approximately 30 % in the rest of Europe. Teamwork was commonly adopted; 86 % of centres based in Western countries utilised the interdisciplinary model, whilst the multidisciplinary model was utilised in Eastern based countries (p = 0.046). Conclusion This survey is the first to provide data about organisational aspects of physiotherapy for people with MS across Europe. Overall, care in key organisational aspects of service provision is broadly similar across regions, although some variations, for example the models of teamwork utilised, are apparent. Organisational framework specifics should be considered anytime a multi-centre study is conducted and results from such studies are applied.PubMedWoSScopu
A global view of the OCA2-HERC2 region and pigmentation
Mutations in the gene OCA2 are responsible for oculocutaneous albinism type 2, but polymorphisms in and around OCA2 have also been associated with normal pigment variation. In Europeans, three haplotypes in the region have been shown to be associated with eye pigmentation and a missense SNP (rs1800407) has been associated with green/hazel eyes (Branicki et al. in Ann Hum Genet 73:160–170, 2009). In addition, a missense mutation (rs1800414) is a candidate for light skin pigmentation in East Asia (Yuasa et al. in Biochem Genet 45:535–542, 2007; Anno et al. in Int J Biol Sci 4, 2008). We have genotyped 3,432 individuals from 72 populations for 21 SNPs in the OCA2-HERC2 region including those previously associated with eye or skin pigmentation. We report that the blue-eye associated alleles at all three haplotypes were found at high frequencies in Europe; however, one is restricted to Europe and surrounding regions, while the other two are found at moderate to high frequencies throughout the world. We also observed that the derived allele of rs1800414 is essentially limited to East Asia where it is found at high frequencies. Long-range haplotype tests provide evidence of selection for the blue-eye allele at the three haplotyped systems but not for the green/hazel eye SNP allele. We also saw evidence of selection at the derived allele of rs1800414 in East Asia. Our data suggest that the haplotype restricted to Europe is the strongest marker for blue eyes globally and add further inferential evidence that the derived allele of rs1800414 is an East Asian skin pigmentation allele
Toxic Diatom Aldehydes Affect Defence Gene Networks in Sea Urchins.
Marine organisms possess a series of cellular strategies to counteract the negative effects of toxic compounds, including the massive reorganization of gene expression networks. Here we report the modulated dose-dependent response of activated genes by diatom polyunsaturated aldehydes (PUAs) in the sea urchin Paracentrotus lividus. PUAs are secondary metabolites deriving from the oxidation of fatty acids, inducing deleterious effects on the reproduction and development of planktonic and benthic organisms that feed on these unicellular algae and with anti-cancer activity. Our previous results showed that PUAs target several genes, implicated in different functional processes in this sea urchin. Using interactomic Ingenuity Pathway Analysis we now show that the genes targeted by PUAs are correlated with four HUB genes, NF-κB, p53, δ-2-catenin and HIF1A, which have not been previously reported for P. lividus. We propose a working model describing hypothetical pathways potentially involved in toxic aldehyde stress response in sea urchins. This represents the first report on gene networks affected by PUAs, opening new perspectives in understanding the cellular mechanisms underlying the response of benthic organisms to diatom exposure
Fish oil administration in older adults: is there potential for adverse events? A systematic review of the literature
ackground: Omega-3 (n-3) fatty acid supplementation is becoming increasingly popular. However given its
antithrombotic properties the potential for severe adverse events (SAE) such as bleeding has safety implications,
particularly in an older adult population. A systematic review of randomized control trials (RCT) was conducted to
explore the potential for SAE and non-severe adverse events (non-SAE) associated with n-3 supplementation in
older adults.
Methods: A comprehensive search strategy using Medline and a variety of other electronic sources was conducted.
Studies investigating the oral administration of n-3 fish oil containing eicosapentaenoic acid (EPA), docosahexaenoic
acid (DHA) or both against a placebo were sourced. The primary outcome of interest included reported SAE
associated with n-3 supplementation. Chi-square analyses were conducted on the pooled aggregate of AEs.
Results: Of the 398 citations initially retrieved, a total of 10 studies involving 994 older adults aged ≥60 years were
included in the review. Daily fish oil doses ranged from 0.03 g to 1.86 g EPA and/or DHA with study durations
ranging from 6 to 52 weeks. No SAE were reported and there were no significant differences in the total AE rate
between groups (n-3 intervention group: 53/540; 9.8%; placebo group: 28/454; 6.2%; p= 0.07). Non-SAE relating to
gastrointestinal (GI) disturbances were the most commonly reported however there was no significant increase in
the proportion of GI disturbances reported in participants randomized to the n-3 intervention (n-3 intervention
group: 42/540 (7.8%); placebo group: 24/454 (5.3%); p= 0.18).
Conclusions: The potential for AEs appear mild-moderate at worst and are unlikely to be of clinical significance. The
use of n-3 fatty acids and the potential for SAE should however be further researched to investigate whether this
evidence is consistent at higher doses and in other populations. These results also highlight that well-documented data
outlining the potential for SAE following n-3 supplementation are limited nor adequately reported to draw definitive
conclusions concerning the safety associated with n-3 supplementation. A more rigorous and systematic approach for
monitoring and recording AE data in clinical settings that involve n-3 supplementation is required.The authors would like to acknowledge funding
provided for the ongoing ATLANTIC randomized controlled trial supported
by the National Health and Medical Research Council (NHMRC), Australia
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