Patient and observer reported outcome measures to evaluate health-related quality of life in inherited metabolic diseases: a scoping review

Background

Health-related Quality of Life (HrQoL) is a multidimensional measure, which has gained clinical and social relevance. Implementation of a patient-centred approach to both clinical research and care settings, has increased the recognition of patient and/or observer reported outcome measures (PROMs or ObsROMs) as informative and reliable tools for HrQoL assessment. Inherited Metabolic Diseases (IMDs) are a group of heterogeneous conditions with phenotypes ranging from mild to severe and mostly lacking effective therapies. Consequently, HrQoL evaluation is particularly relevant.

Objectives

We aimed to: (1) identify patient and/or caregiver-reported HrQoL instruments used among IMDs; (2) identify the main results of the application of each HrQoL tool and (3) evaluate the main limitations of HrQoL instruments and study design/methodology in IMDs.

Methods

A scoping review was conducted using methods outlined by Arksey and O’Malley. Additionally, we critically analysed each article to identify the HrQoL study drawbacks.

Results

Of the 1954 studies identified, 131 addressed HrQoL of IMDs patients using PROMs and/or ObsROMs, both in observational or interventional studies. In total, we identified 32 HrQoL instruments destined to self- or proxy-completion; only 2% were disease-specific. Multiple tools (both generic and disease-specific) proved to be responsive to changes in HrQoL; the SF-36 and PedsQL questionnaires were the most frequently used in the adult and pediatric populations, respectively. Furthermore, proxy data often demonstrated to be a reliable approach complementing self-reported HrQoL scores. Nevertheless, numerous limitations were identified especially due to the rarity of these conditions.

Conclusions

HrQoL is still not frequently assessed in IMDs. However, our results show successful examples of the use of patient-reported HrQoL instruments in this field. The importance of HrQoL measurement for clinical research and therapy development, incites to further research in HrQoL PROMs’ and ObsROMs’ creation and validation in IMDs.

     

Intraspecific traits change biodiversity effects on ecosystem functioning under metal stress

Studies investigating the impacts of biodiversity loss on ecosystem processes have often reached different conclusions, probably because insufficient attention has been paid to some aspects including (1) which biodiversity measure (e.g., species number, species identity or trait) better explains ecosystem functioning, (2) the mechanisms underpinning biodiversity effects, and (3) how can environmental context modulates biodiversity effects. Here, we investigated how species number (one to three species) and traits of aquatic fungal decomposers (by replacement of a functional type from an unpolluted site by another from a metal-polluted site) affect fungal production (biomass acumulation) and plant litter decomposition in the presence and absence of metal stress. To examine the putative mechanisms that explain biodiversity effects, we determined the contribution of each fungal species to the total biomass produced in multicultures by real-time PCR. In the absence of metal, positive diversity effects were observed for fungal production and leaf decomposition as a result of species complementarity. Metal stress decreased diversity effects on leaf decomposition in assemblages containing the functional type from the unpolluted site, probably due to competitive interactions between fungi. However, dominance effect maintained positive diversity effects under metal stress in assemblages containing the functional type from the metal-polluted site. These findings emphasize the importance of intraspecific diversity in modulating diversity effects under metal stress, providing evidence that trait-based diversity measures should be incorporated when examining biodiversity effects.     

Elevated temperature may intensify the positive effects of nutrients on microbial decomposition in streams

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Essential oils from neotropical Myrtaceae: chemical diversity and biological properties

Myrtaceae family (121 genera, 3800-5800 spp.) is one of the most important families in tropical forests. They are aromatic trees or shrubs, which frequently produce edible fruits. In the neotropics, ca. 1000 species were found. Several members of this family are used in folk medicine, mainly as an antidiarrheal, antimicrobial, antioxidant, cleanser, antirheumatic, and anti-inflammatory agent and to decrease the blood cholesterol. In addition, some fruits are eaten fresh or used to make juices, liqueurs, and sweets very much appreciated by people. The flavor composition of some fruits belonging to the Myrtaceae family has been extensively studied due to their pleasant and intense aromas. Most of the essential oils of neotropical Myrtaceae analyzed so far are characterized by predominance of sesquiterpenes, some with important biological properties. In the present work, chemical and pharmacological studies carried out on neotropical Myrtaceae species are reviewed, based on original articles published since 1980. The uses in folk medicine and chemotaxonomic importance of secondary metabolites are also briefly discussed.     

Excess amino acid polymorphism in mitochondrial DNA: contrasts among genes from Drosophila, mice, and humans

Recent studies of mitochondrial DNA (mtDNA) variation in mammals and Drosophila have shown an excess of amino acid variation within species (replacement polymorphism) relative to the number of silent and replacement differences fixed between species. To examine further this pattern of nonneutral mtDNA evolution, we present sequence data for the ND3 and ND5 genes from 59 lines of Drosophila melanogaster and 29 lines of D. simulans. Of interest are the frequency spectra of silent and replacement polymorphisms, and potential variation among genes and taxa in the departures from neutral expectations. The Drosophila ND3 and ND5 data show no significant excess of replacement polymorphism using the McDonald-Kreitman test. These data are in contrast to significant departures from neutrality for the ND3 gene in mammals and other genes in Drosophila mtDNA (cytochrome b and ATPase 6). Pooled across genes, however, both Drosophila and human mtDNA show very significant excesses of amino acid polymorphism. Silent polymorphisms at ND5 show a significantly higher variance in frequency than replacement polymorphisms, and the latter show a significant skew toward low frequencies (Tajima's D = -1.954). These patterns are interpreted in light of the nearly neutral theory where mildly deleterious amino acid haplotypes are observed as ephemeral variants within species but do not contribute to divergence. The patterns of polymorphism and divergence at charge-altering amino acid sites are presented for the Drosophila ND5 gene to examine the evolution of functionally distinct mutations. Excess charge-altering polymorphism is observed at the carboxyl terminal and excess charge-altering divergence is detected at the amino terminal. While the mildly deleterious model fits as a net effect in the evolution of nonrecombining mitochondrial genomes, these data suggest that opposing evolutionary pressures may act on different regions of mitochondrial genes and genomes.      

Notch Signalling Is Required for the Formation of Structurally Stable Muscle Fibres in Zebrafish

Background

Accurate regulation of Notch signalling is central for developmental processes in a variety of tissues, but its function in pectoral fin development in zebrafish is still unknown.

Methodology/Principal Findings

Here we show that core elements necessary for a functional Notch pathway are expressed in developing pectoral fins in or near prospective muscle territories. Blocking Notch signalling at different levels of the pathway consistently leads to the formation of thin, wavy, fragmented and mechanically weak muscles fibres and loss of stress fibres in endoskeletal disc cells in pectoral fins. Although the structural muscle genes encoding Desmin and Vinculin are normally transcribed in Notch-disrupted pectoral fins, their proteins levels are severely reduced, suggesting that weak mechanical forces produced by the muscle fibres are unable to stabilize/localize these proteins. Moreover, in Notch signalling disrupted pectoral fins there is a decrease in the number of Pax7-positive cells indicative of a defect in myogenesis.

Conclusions/Significance

We propose that by controlling the differentiation of myogenic progenitor cells, Notch signalling might secure the formation of structurally stable muscle fibres in the zebrafish pectoral fin.     

Characterization of an acetylated heteroxylan from Eucalyptus globulus Labill

A heteroxylan was isolated from Eucalyptus globulus wood by extraction of peracetic acid delignified holocellulose with dimethyl sulfoxide. Besides (1-->4)-linked beta-D-xylopyranosyl units of the backbone and short side chains of terminal (1-->2)-linked 4-O-methyl-alpha-D-glucuronosyl residues (MeGlcA) in a 1:10 molar ratio, this hemicellulose contained galactosyl and glucosyl units attached at O-2 of MeGlcA originating from rhamnoarabinogalactan and glucan backbones, respectively. About 30% of MeGlcA units were branched at O-2. The O-acetyl-(4-O-methylglucurono)xylan showed an acetylation degree of 0.61, as determined by 1H NMR spectroscopy, and a weight-average molecular weight (M(w)) of about 36 kDa (P=1.05) as revealed from size-exclusion chromatography (SEC) analysis. About half of the beta-D-xylopyranosyl units of the backbone were found as acetylated moieties at O-3 (34 mol%), O-2 (15 mol%) or O-2,3 (6 mol%). Practically, all beta-D-xylopyranosyl units linked at O-2 with MeGlcA residues were 3-O-acetylated (10 mol%).     

Temperature alters interspecific relationships among aquatic fungi

Temperature is a key factor in determining the structure and performance of fungal assemblages on decomposing plant litter in streams. However, little is known of how temperature affects interspecific relationships among fungi. We compared the growth of four aquatic hyphomycetes co-occurring in temperate streams, in monocultures and all species combinations when exposed to five temperatures from 11 to 27 °C. In monocultures, maximum growth rates of Heliscus submersus, Lunulospora curvula and Varicosporium elodeae occurred at 27 °C whereas Articulospora tetracladia had the lowest growth rate. At 27 °C, the increase in species diversity had no effect on the growth of V. elodeae, increased the growth of H. submersus and L. curvula, and decreased the growth of A. tetracladia. Results suggest that within a species' optimal temperature range the growth of that species increases with higher fungal diversity, while outside this range growth decreases with diversity.