Anthropometrics and fat mass, but not fat-free mass, are compromised in infants requiring parenteral nutrition after neonatal intestinal surgery

BACKGROUND: Children with intestinal failure (IF) receiving long-term parenteral nutrition (PN) have altered body composition (BC), but data on BC changes from start of PN onwards are lacking. OBJECTIVE: We aimed to assess growth and BC in infants after neonatal intestinal surgery necessitating PN and at risk for IF, and to explore associations with clinical parameters. DESIGN: Prospective cohort study in infants after intestinal surgery. IF was defined as PN-dependency for > 60 days. Standard deviation scores (SDS) for anthropometry were calculated until 6 months corrected age. In a subgroup, fat mass (FM) and fat-free mass (FFM) were measured with air-displacement plethysmography at 2- and 6-months corrected age. SDS for length-adjusted FM index and FFM index were calculated. Associations between cumulative amount of PN and BC parameters were analyzed with linear mixed-effect models. RESULTS: Ninety-five neonates were included (54% male, 35% born < 32 weeks). Thirty-nine infants (41%) had IF. Studied infants had compromised anthropometric parameters during follow-up. At 6 months corrected age, they remained smaller (median weight-for-age SDS -0.9 [interquartile range -1.5, 0.1], P < 0.001) than the normal population. In 57 infants, 93 BC measurements were performed. FM index SDS was lower than in healthy infants at 2- and 6-months corrected age (-0.9 [-1.6, -0.3], P < 0.001 and -0.7 [-1.3, 0.1], P = 0.001, respectively), but FFM index SDS did not differ. A higher cumulative amount of PN predicted higher FM index in female infants but lower FM index in male infants. CONCLUSIONS: In this cohort of infants receiving PN after intestinal surgery, compromised anthropometrics, decreased FM and adequate FFM were observed during the first 6 months. Male and female infants seemed to respond differently to PN when it comes to FM index. Continuing growth monitoring after 6 months of age is strongly recommended, while further research should explore the benefit of incorporating ongoing BC monitoring during follow-up.Clinical Trial Registration: Dutch Trial Register NTR6080, https://www.trialregister.nl/trial/5892

Fitness efficacy of vibratory exercise compared to walking in postmenopausal women

In this study, we compared the efficacy of 8 months of low-frequency vibration and a walk-based program in health-related fitness. Twenty-seven postmenopausal women were randomly assigned into two groups: whole-body vibration (WBV) group (n = 18) performed three times/week a static exercise on a vibration platform (6 sets of 1-min with 1 min of rest, with a 12.6 Hz of frequency and an amplitude of 3 mm); walk-based program (WP) group (n = 18) performed three times/week a 60-min of walk activity at 70-75% of maximal heart rate. A health-related battery of tests was applied. Maximal unilateral concentric and eccentric isokinetic torque of the knee extensors was recorded by an isokinetic dynamometer. Physical fitness was measured using the following tests: vertical jump test, chair rise test and maximal walking speed test over 4 m. Maximal unilateral isokinetic strength was measured in the knee extensors in concentric actions at 60 and 300 degrees /s, and eccentric action at 60 degrees /s. After 8 months, the WP improved the time spent to walk 4 m (20%) and to perform the chair rise test (12%) compared to the WBV group (P = 0.006, 0.002, respectively). In contrast, the comparison of the changes in vertical jump showed the higher effectiveness of the vibratory exercise in 7% (P = 0.025). None of exercise programs showed change on isokinetic measurements. These results indicate that both programs differed in the main achievements and could be complementary to prevent lower limbs muscle strength decrease as we age [ISRCTN76235671]

Remifentanil patient controlled analgesia versus epidural analgesia in labour. A multicentre randomized controlled trial

Contains fulltext : 109349.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Pain relief during labour is a topic of major interest in the Netherlands. Epidural analgesia is considered to be the most effective method of pain relief and recommended as first choice. However its uptake by pregnant women is limited compared to other western countries, partly as a result of non-availability due to logistic problems. Remifentanil, a synthetic opioid, is very suitable for patient controlled analgesia. Recent studies show that epidural analgesia is superior to remifentanil patient controlled analgesia in terms of pain intensity score; however there was no difference in satisfaction with pain relief between both treatments. METHODS/DESIGN: The proposed study is a multicentre randomized controlled study that assesses the cost-effectiveness of remifentanil patient controlled analgesia compared to epidural analgesia. We hypothesize that remifentanil patient controlled analgesia is as effective in improving pain appreciation scores as epidural analgesia, with lower costs and easier achievement of 24 hours availability of pain relief for women in labour and efficient pain relief for those with a contraindication for epidural analgesia.Eligible women will be informed about the study and randomized before active labour has started. Women will be randomly allocated to a strategy based on epidural analgesia or on remifentanil patient controlled analgesia when they request pain relief during labour. Primary outcome is the pain appreciation score, i.e. satisfaction with pain relief.Secondary outcome parameters are costs, patient satisfaction, pain scores (pain-intensity), mode of delivery and maternal and neonatal side effects.The economic analysis will be performed from a short-term healthcare perspective. For both strategies the cost of perinatal care for mother and child, starting at the onset of labour and ending ten days after delivery, will be registered and compared. DISCUSSION: This study, considering cost effectiveness of remifentanil as first choice analgesia versus epidural analgesia, could strongly improve the care for 180.000 women, giving birth in the Netherlands yearly by giving them access to pain relief during labour, 24 hours a day. TRIAL REGISTRATION NUMBER: Dutch Trial Register NTR2551, http://www.trialregister.nl

Segmental Duplications Arise from Pol32-Dependent Repair of Broken Forks through Two Alternative Replication-Based Mechanisms

The propensity of segmental duplications (SDs) to promote genomic instability is of increasing interest since their involvement in numerous human genomic diseases and cancers was revealed. However, the mechanism(s) responsible for their appearance remain mostly speculative. Here, we show that in budding yeast, replication accidents, which are most likely transformed into broken forks, play a causal role in the formation of SDs. The Pol32 subunit of the major replicative polymerase Polδ is required for all SD formation, demonstrating that SDs result from untimely DNA synthesis rather than from unequal crossing-over. Although Pol32 is known to be required for classical (Rad52-dependant) break-induced replication, only half of the SDs can be attributed to this mechanism. The remaining SDs are generated through a Rad52-independent mechanism of template switching between microsatellites or microhomologous sequences. This new mechanism, named microhomology/microsatellite-induced replication (MMIR), differs from all known DNA double-strand break repair pathways, as MMIR-mediated duplications still occur in the combined absence of homologous recombination, microhomology-mediated, and nonhomologous end joining machineries. The interplay between these two replication-based pathways explains important features of higher eukaryotic genomes, such as the strong, but not strict, association between SDs and transposable elements, as well as the frequent formation of oncogenic fusion genes generating protein innovations at SD junctions

Asymmetric reproductive isolation between terminal forms of the salamander ring species Ensatina eschscholtzii revealed by fine-scale genetic analysis of a hybrid zone

<p>Abstract</p> <p>Background</p> <p>Ring species, exemplified by salamanders of the <it>Ensatina eschscholtzii </it>complex, represent a special window into the speciation process because they allow the history of species formation to be traced back in time through the geographically differentiated forms connecting the two terminal forms of the ring. Of particular interest is the nature and extent of reproductive isolation between the geographically terminal forms, in this case <it>E. e. eschscholtzii </it>and <it>E. e. klauberi</it>. Previous studies have documented infrequent hybridization at the end of the ring. Here, we report the first fine-scale genetic analysis of a hybrid zone between the terminal forms in southern California using individual-based Bayesian analyses of multilocus genetic data to estimate levels and direction of hybridization and maximum-likelihood analysis of linkage disequilibrium and cline shape to make inferences about migration and selection in the hybrid zone.</p> <p>Results</p> <p>The center of the hybrid zone has a high proportion of hybrids, about half of which were classified as F1s. Clines are narrow with respect to dispersal, and there are significant deviations from Hardy-Weinberg equilibrium as well as nonrandom associations (linkage disequilibria) between alleles characteristic of each parental type. There is cytonuclear discordance, both in terms of introgression and the geographic position of mitochondrial versus nuclear clines. Genetic disequilibrium is concentrated on the <it>eschscholtzii </it>side of the zone. Nearly all hybrids possess <it>klauberi </it>mtDNA, indicating that most hybrids are formed from female <it>klauberi </it>mating with male <it>eschscholtzii </it>or male hybrids (but not vice versa).</p> <p>Conclusions</p> <p>Our results are consistent with a tension zone trapped at an ecotone, with gene combinations characteristic of <it>klauberi </it>showing up on the <it>eschscholtzii </it>side of the zone due to asymmetric hybridization. We suggest that the observed asymmetry is best explained by increased discriminatory power of <it>eschscholtzii </it>females, or asymmetric postzygotic isolation. The relatively high frequency of hybrids, particularly F1s, contrasts with other contacts between the terminal forms, and with other contacts between other divergent <it>Ensatina </it>lineages, highlighting the diverse outcomes of secondary contact within a single species complex.</p

Next-generation mitogenomics: A comparison of approaches applied to caecilian amphibian phylogeny

Mitochondrial genome (mitogenome) sequences are being generated with increasing speed due to the advances of next-generation sequencing (NGS) technology and associated analytical tools. However, detailed comparisons to explore the utility of alternative NGS approaches applied to the same taxa have not been undertaken. We compared a 'traditional' Sanger sequencing method with two NGS approaches (shotgun sequencing and non-indexed, multiplex amplicon sequencing) on four different sequencing platforms (Illumina's HiSeq and MiSeq, Roche's 454 GS FLX, and Life Technologies' Ion Torrent) to produce seven (near-) complete mitogenomes from six species that form a small radiation of caecilian amphibians from the Seychelles. The fastest, most accurate method of obtaining mitogenome sequences that we tested was direct sequencing of genomic DNA (shotgun sequencing) using the MiSeq platform. Bayesian inference and maximum likelihood analyses using seven different partitioning strategies were unable to resolve compellingly all phylogenetic relationships among the Seychelles caecilian species, indicating the need for additional data in this case

Speciation in little: the role of range and body size in the diversification of Malagasy mantellid frogs

<p>Abstract</p> <p>Background</p> <p>The rate and mode of lineage diversification might be shaped by clade-specific traits. In Madagascar, many groups of organisms are characterized by tiny distribution ranges and small body sizes, and this high degree of microendemism and miniaturization parallels a high species diversity in some of these groups. We here investigate the geographic patterns characterizing the radiation of the frog family Mantellidae that is virtually endemic to Madagascar. We integrate a newly reconstructed near-complete species-level timetree of the Mantellidae with georeferenced distribution records and maximum male body size data to infer the influence of these life-history traits on each other and on mantellid diversification.</p> <p>Results</p> <p>We reconstructed a molecular phylogeny based on nuclear and mitochondrial DNA for 257 species and candidate species of the mantellid frog radiation. Based on this phylogeny we identified 53 well-supported pairs of sister species that we used for phylogenetic comparative analyses, along with whole tree-based phylogenetic comparative methods. Sister species within the Mantellidae diverged at 0.2-14.4 million years ago and more recently diverged sister species had geographical range centroids more proximate to each other, independently of their current sympatric or allopatric occurrence. The largest number of sister species pairs had non-overlapping ranges, but several examples of young microendemic sister species occurring in full sympatry suggest the possibility of non-allopatric speciation. Range sizes of species included in the sister species comparisons increased with evolutionary age, as did range size differences between sister species, which rejects peripatric speciation. For the majority of mantellid sister species and the whole mantellid radiation, range and body sizes were associated with each other and small body sizes were linked to higher mitochondrial nucleotide substitution rates and higher clade diversity. In contrast, small range sizes were unexpectedly associated with a slow-down of mitochondrial substitution rates.</p> <p>Conclusions</p> <p>Based on these results we define a testable hypothesis under which small body sizes result in limited dispersal capabilities and low physiological tolerances, causing smaller and more strongly fragmented ranges. This can be thought to facilitate reproductive isolation and thus favor speciation. Contrary to the expectation of the faster speciation of such microendemic phenotype species, we only found small body sizes of mantellid frogs to be linked to higher diversification and substitution rates, but not small range sizes. A joint analysis of various species-rich regional anuran radiations might provide enough species with all combinations of range and body sizes for a more conclusive test of this hypothesis.</p