Early Neurodevelopmental Findings Predict School Age Cognitive Abilities in Duchenne Muscular Dystrophy: A Longitudinal Study

Objective

Neurodevelopmental and cognitive difficulties are known to occur frequently in boys with Duchenne muscular dystrophy but so far none of the published studies have reported both early neurodevelopmental assessments and cognitive tests in the same cohort. The aim of the present longitudinal study was to establish the correlation between early neurodevelopmental assessments performed in preschool boys and the cognitive scales performed at school age or later.

Methods

We performed cognitive tests at school age (mean age 5.7 year ±1.7 SD) (69 months+19 SD) in a cohort of Duchenne boys, previously assessed using the Griffiths scales before the age of 4 years (mean age when the Griffiths scales were performed 30 months ±8.9 SD).

Results

The range of total Developmental quotients on the Griffiths ranged between 56 and 116 (mean 89 ± 15.6 SD). The total Intelligence Quotients on the Wechsler scales ranged between 35 and 119 (mean 87 ± 17.2 SD). There was a significant correlation between the findings on the two scales. P = <0.0001. When we subdivided the cohort according to site of mutations, there was a difference between boys with mutations upstream exon 44 and those with mutations in exon 44–45 affecting Dp140 on both Developmental and Intelligence Quotient (p 0.01 and p 0,003 respectively).

Conclusions

Our results confirm that Duchenne boys tend to slightly underperform on both neurodevelopmental and cognitive assessments. Early neurodevelopmental findings correlated with the cognitive results obtained at school age with a clear concordance between subscales exploring similar domains on the two scales.     

Host spatial structure and disperser activity determine mistletoe infection patterns

What processes and factors are responsible for species distribution are long-standing questions in ecology and a key element for conservation and management. Mistletoes provide the opportunity to study a forest species whose occurrence is expected to be constrained by multiple factors as a consequence of their life form. We studied the mistletoe Tristerix corymbosus (Loranthaceae) on its most common hosts species in northwest Patagonia. The seeds of this mistletoe are almost exclusively dispersed by the small arboreal and endemic marsupial Dromiciops gliroides (Microbiotheridae). We assessed the underlying causes of plant spatial patterns through point pattern analysis and we used different variables that characterize the neighborhood around each host to analyze the relative effect of host availability, potential for disperser movement and canopy light conditions. We found that potential hosts were strongly aggregated and that the three most common host species were distributed independent of each other. Considering all host species together, infected and non-infected host were individually aggregated but segregated from each other. The aggregated pattern of infected hosts could be explained in part by the template of potential hosts distribution, but was subsequently modulated by the activity of the mistletoe disperser. Potential for disperser movement, the proximity to reproductive mistletoes and habitat complexity, increased mistletoe infection probability. However, neighboring host availability decreased mistletoe infection probability, and tree DBH (used as surrogate for light conditions) had no detectable effect. Our results suggested that the distribution of mistletoe infection was determined by the structure of potential host populations and by the marsupial disperser activity. Compared to bird dispersed mistletoes, the scale of the infection was smaller and the proximity to reproductive mistletoes and habitat complexity were important for seed arrival and infection. The interplay between landscape structure and disperser activity determine the spatial structure of mistletoe future generations.     

Establishment and dispersal of the biological control weevil Rhinoncomimus latipes on mile-a-minute weed, Persicaria perfoliata

Mile-a-minute weed, Persicaria perfoliata (L.) H. Gross (Polygonaceae), is an annual vine from Asia that has invaded the eastern US where it can form dense monocultures and outcompete other vegetation in a variety of habitats. The host-specific Asian weevil Rhinoncomimus latipes Korotyaev (Coleoptera: Curculionidae) was first released in the US in 2004 as part of a classical biological control program. The weevil was intensively monitored in three release arrays over 4 years, and field cages at each site were used to determine the number of generations produced. The weevil established at all three sites and produced three to four generations before entering a reproductive diapause in late summer. Weevils dispersed at an average rate of 1.5–2.9 m wk⁻¹ through the 50 m diameter arrays, which had fairly contiguous mile-a-minute cover. Weevils dispersing in the broader, more variable landscape located both large monocultures and small isolated patches of mile-a-minute 600–760 m from the release within 14 months. Weevil density ranged from fewer than 10 to nearly 200 weevils m⁻² mile-a-minute weed. Mile-a-minute cover decreased at the site with the highest weevil density. The production of P. perfoliata seed clusters decreased with increasing weevil populations at two sites, and seedling production declined over time at two sites by 75% and 87%. The ability of the weevil to establish, produce multiple generations per season, disperse to new patches, and likelihood of having an impact on plants in the field suggests that R. latipes has the potential to be a successful biological control agent.     

No Evidence of Sexual Risk Compensation in the iPrEx Trial of Daily Oral HIV Preexposure Prophylaxis

Objective

Preexposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) reduced HIV acquisition in the iPrEx trial among men who have sex with men and transgender women. Self-reported sexual risk behavior decreased overall, but may be affected by reporting bias. We evaluated potential risk compensation using biomarkers of sexual risk behavior.

Design and methods

Sexual practices were assessed at baseline and quarterly thereafter; perceived treatment assignment and PrEP efficacy beliefs were assessed at 12 weeks. Among participants with ≥1 follow-up behavioral assessment, sexual behavior, syphilis, and HIV infection were compared by perceived treatment assignment, actual treatment assignment, and perceived PrEP efficacy.

Results

Overall, acute HIV infection and syphilis decreased during follow-up. Compared with participants believing they were receiving placebo, participants believing they were receiving FTC/TDF reported more receptive anal intercourse partners prior to initiating drug (12.8 vs. 7.7, P = 0.04). Belief in receiving FTC/TDF was not associated with an increase in receptive anal intercourse with no condom (ncRAI) from baseline through follow-up (risk ratio [RR] 0.9, 95% confidence interval [CI]: 0.6–1.4; P = 0.75), nor with a decrease after stopping study drug (RR 0.8, 95% CI: 0.5–1.3; P = 0.46). In the placebo arm, there were trends toward lower HIV incidence among participants believing they were receiving FTC/TDF (incidence rate ratio [IRR] 0.8, 95% CI: 0.4–1.8; P = 0.26) and also believing it was highly effective (IRR 0.5, 95% CI: 0.1–1.7; P = 0.12).

Conclusions

There was no evidence of sexual risk compensation in iPrEx. Participants believing they were receiving FTC/TDF had more partners prior to initiating drug, suggesting that risk behavior was not a consequence of PrEP use.     

Geographic variation in fruit colour is associated with contrasting seed disperser assemblages in a south‐Andean mistletoe

Fruit colour influences fruit choice by seed dispersers. The mistletoe Tristerix corymbosus (Loranthaceae) produces mature fruits of two different colours in two different biomes: yellow in the Chilean matorral and green in the temperate forest of southern South America. We conducted field surveys to establish the association between fruit colour and disperser identity throughout the entire geographical range of T. corymbosus. We selected 22 populations, eight of which were located in the Chilean matorral and 14 in the temperate forest south of the matorral. To identify the seed dispersers of the mistletoe we used direct observation, camera traps, and live‐trapping of small mammals. We also report experiments to assess fruit selection by seed dispersers based on differences in colour. The assemblages of dispersers of T. corymbosus differ between the two biomes: yellow fruits in Chilean matorral are exclusively dispersed by three bird species while green fruits in the temperate forest are exclusively dispersed by a marsupial. The differences in the assemblages of seed dispersers can be explained by differences in food‐finding strategies between the two assemblages. Green fruits in temperate forest are not easily detected by birds, while colour might not be an important cue for the marsupial because it is nocturnal and uses other senses to locate food. We propose that the association between the marsupial and the green‐fruited mistletoe constitutes an ecological fitting rather than the outcome of a co‐evolutionary process. The marsupial might have allowed the mistletoe T. corymbosus to retain green coloration in mature fruit, a condition to which it is preadapted by a slower ripening process in temperate forest populations.     

Activation of pregnane X receptor disrupts glucocorticoid and mineralocorticoid homeostasis

The pregnane X receptor (PXR) was isolated as a xenobiotic receptor that regulates responses to various xenobiotic agents. In this study, we show that PXR plays an important endobiotic role in adrenal steroid homeostasis. Activation of PXR by genetic (transgene) or pharmacological (ligand, such as rifampicin) markedly increased plasma concentrations of corticosterone and aldosterone, the respective primary glucocorticoid and mineralocorticoid in rodents. The increased levels of corticosterone and aldosterone were associated with activation of adrenal steroidogenic enzymes, including cytochrome P450 (CYP)11a1, CYP11b1, CYP11b2, and 3beta-hydroxysteroid dehydrogenase. The PXR-activating transgenic mice also exhibited hypertrophy of the adrenal cortex, loss of glucocorticoid circadian rhythm, and lack of glucocorticoid responses to psychogenic stress. Interestingly, the transgenic mice had normal pituitary secretion of ACTH and the corticosterone-suppressing effect of dexamethasone was intact, suggesting a functional hypothalamus-pituitary-adrenal axis despite a severe disruption of adrenal steroid homeostasis. The ACTH-independent hypercortisolism in the PXR-activating transgenic mice is reminiscent of the pseudo-Cushing's syndrome in patients. The glucocorticoid effect appears to be PXR specific, as the activation of constitutive androstane receptor in transgenic mice had little effect. We propose that PXR is a potential endocrine disrupting factor that may have broad implications in steroid homeostasis and drug-hormone interactions.     

Relationships between serpentine soils and vegetation in a xeric inner-Alpine environment

Aims

In serpentinitic areas non-endemic plants suffer from the serpentine syndrome, due to high Ni and Mg concentrations, low nutrients and Ca/Mg ratio. We evaluated the environment-soil-vegetation relationships in a xeric inner-alpine area (NW Italy), where the inhibited pedogenesis should enhance parent material influences on vegetation.

Methods

Site conditions, topsoil properties, plant associations and species on and off serpentinite were statistically associated (51 sites).

Results

Serpentine soils had higher Mg and Ni concentrations, but did not differ from non-serpentine ones in nutrient contents. The 15 vegetation clusters often showed substrate specificity. Two components of the Canonical Analysis of Principal Coordinates, respectively related to Mg and to Ni and heat load, identified serpentine vegetation. Random Forests showed that several species were positively correlated with Ni and/or Ca/Mg or Mg, some were negatively associated with high Ni, Mg excess affected only few species. Considering only serpentine sites, nutrients and microclimate were most important.

Conclusions

Ni excess most often precludes the presence of plant species on serpentinite, while an exclusion due to Mg is rarer. Endemic species are mostly adapted to both factors. Nutrient scarcity was not specific of serpentine soils in the considered environment. Considering only serpentine sites, nutrient and microclimatic gradients drove vegetation variability.     

The effect of short-term flooding on the sap flow, gas exchange and hydraulic conductivity of young apricot trees

The effect of short-term flooding was examined in 2-year-old apricot trees (Prunus armeniaca cv. Búlida). Six apricot trees of similar appearance were submitted to two treatments: three were irrigated daily, while the others were flooded for a period of 50 h by submerging the pots in plastic water tanks. The trees were removed from the water, drained and then placed in the same conditions as the control plants. A decrease in transpiration in the flooded trees with respect to the control plants was evident. The daily pattern of soil O₂ concentration and plant hydraulic resistance followed a similar trend during the flooding. However, this relationship was not maintained throughout the experiment, since the O₂ values increased rapidly when the waterlogging ceased, while plant hydraulic resistance only recovered at the end of the experiment when the original root system, damaged by flooded conditions, was replaced with new roots. In flooded trees, the midday leaf water potential decreased progressively from the beginning of flooding, but gradually recovered when the waterlogging ceased. Leaf conductance values of treated plants were slow to recover, reaching values of the control plants 8 days after the leaf water potential had recovered. The close relationship observed during most of the experiment between the leaf water parameters, leaf conductance and plant hydraulic conductance indicate that hydraulic messages are likely to play a dominant role in co-ordinating the observed responses of the shoot.