Parasitic nematodes are highly diverse and common, infecting virtually all animal species, and the importance of their roles in natural ecosystems is increasingly becoming apparent. How genes flow ...within and among populations of these parasites - their population genetics - has profound implications for the epidemiology of host infection and disease, and for the response of parasite populations to selection pressures. The population genetics of nematode parasites of wild animals may have consequences for host conservation, or influence the risk of zoonotic disease. Host movement has long been recognised as an important determinant of parasitic nematode population genetic structure, and recent research has also highlighted the importance of nematode life histories, environmental conditions, and other aspects of host ecology. Commonly, factors influencing parasitic nematode population genetics have been studied in isolation, such that an integrated view of the drivers of population genetic structure of parasitic nematodes is still lacking. Here, we seek to provide a comprehensive, broad, and integrative picture of these factors in parasitic nematodes of wild animals that will be a useful resource for investigators studying non-model parasitic nematodes in natural ecosystems. Increasingly, new methods of analysing the population genetics of nematodes are becoming available, and we consider the opportunities that these afford in resolving hitherto inaccessible questions of the population genetics of these important animals.
Abstract Purpose We aimed to evaluate the impact of a transition service on clinical and developmental outcomes in adolescent Inflammatory Bowel Disease (IBD) patients on transfer to adult health ...care services. Methods We reviewed the records of IBD patients diagnosed in pediatric care following their transfer/attendance to the adult IBD service. The data on patients who attended the transition service were compared with those who did not pass through the transition service. Results Seventy-two patients were included in the study 41M and 31F. Forty-four patients went through the transition system (Group A), and 28 had no formalized transition arrangement before transfer (Group B). A significantly higher number of Group B patients needed surgery within 2 years of transfer when compared with patients in Group A (46% vs. 25%, p = .01). Sixty-one percent of patients in Group B needed at least one admission within 2 years of transfer when compared with 29% of Group A patients ( p = .002). Nonattendance at clinics was higher in Group B patients with 78% having at least one nonattendance, whereas 29% of Group A failed to attend at least one appointment ( p = .001). In addition, drug compliance rates were higher in the transition group when compared with Group B (89% and 46%, respectively; p = .002). A higher proportion of transitioned patients achieved their estimated maximum growth potential when completing adolescence. There was a trend toward higher dependence on opiates and smoking in Group B patients. Conclusions In adolescent IBD patients, transition care is associated with better disease specific and developmental outcomes. Prospective studies of different models of transition care in IBD are needed.
Several neurochemical systems converge in the prefrontal cortex (PFC) to regulate cognitive and motivated behaviors. A rich network of endogenous opioid peptides and receptors spans multiple PFC cell ...types and circuits, and this extensive opioid system has emerged as a key substrate underlying reward, motivation, affective behaviors, and adaptations to stress. Here, we review the current evidence for dysregulated cortical opioid signaling in the pathogenesis of psychiatric disorders. We begin by providing an introduction to the basic anatomy and function of the cortical opioid system, followed by a discussion of endogenous and exogenous opioid modulation of PFC function at the behavioral, cellular, and synaptic level. Finally, we highlight the therapeutic potential of endogenous opioid targets in the treatment of psychiatric disorders, synthesizing clinical reports of altered opioid peptide and receptor expression and activity in human patients and summarizing new developments in opioid-based medications.
This article is part of the Special Issue on “PFC circuit function in psychiatric disease and relevant models”.
•Opioid signaling in prefrontal cortex is understudied relative to subcortical areas.•PFC opioid receptors are enriched within diverse types of inhibitory interneurons.•Exogenous opiates induce acute and long-term changes in PFC synaptic transmission.•Changes in opioid peptides and receptors are observed in psychiatric diseases.
Recent studies in adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suggest that changes in brain white matter microstructural organization may correlate with core ME/CFS ...symptoms, and represent a potential biomarker of disease. However, this has yet to be investigated in the pediatric ME/CFS population. We examined group differences in macrostructural and microstructural white matter properties, and their relationship with clinical measures, between adolescents recently diagnosed with ME/CFS and healthy controls. Forty‐eight adolescents (25 ME/CFS, 23 controls, mean age 16 years) underwent brain diffusion MRI, and a robust multi‐analytic approach was used to evaluate white and gray matter volume, regional brain volume, cortical thickness, fractional anisotropy, mean/axial/radial diffusivity, neurite dispersion and density, fiber density, and fiber cross section. From a clinical perspective, adolescents with ME/CFS showed greater fatigue and pain, poorer sleep quality, and poorer performance on cognitive measures of processing speed and sustained attention compared with controls. However, no significant group differences in white matter properties were observed, with the exception of greater white matter fiber cross section of the left inferior longitudinal fasciculus in the ME/CFS group compared with controls, which did not survive correction for intracranial volume. Overall, our findings suggest that white matter abnormalities may not be predominant in pediatric ME/CFS in the early stages following diagnosis. The discrepancy between our null findings and white matter abnormalities identified in the adult ME/CFS literature could suggest that older age and/or longer illness duration influence changes in brain structure and brain–behavior relationships that are not yet established in adolescence.
Using diffusion MRI, we observed higher fiber cross section of the left inferior longitudinal fasciculus in adolescents with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) compared with controls. However, this finding did not survive correction for intracranial volume, and there was otherwise overall parity in white matter microstructural indices across all adolescents, regardless of having ME/CFS.
Applied nucleation, mostly based upon planting tree islands, has been proposed as a cost‐effective strategy to meet ambitious global forest and landscape restoration targets.
We review results from a ...15‐year study, replicated at 15 sites in southern Costa Rica, that compares applied nucleation to natural regeneration and mixed‐species tree plantations as strategies to restore tropical forest. We have collected data on planted tree survival and growth, woody vegetation recruitment and structure, seed rain, litterfall, epiphytes, birds, bats and leaf litter arthropods.
Our results indicate that applied nucleation and plantation restoration strategies are similarly effective in enhancing the recovery of most floral and faunal groups, vegetation structure and ecosystem functions, as compared to natural regeneration.
Seed dispersal and woody recruitment are higher in applied nucleation and plantation than natural regeneration treatments; canopy cover has increased substantially in both natural regeneration and applied nucleation treatments; and mortality of planted N‐fixing tree species has increased in recent years. These trends have led to rapid changes in vegetation composition and structure and nutrient cycling.
The applied nucleation strategy is cheaper than mixed‐species tree plantations, but there may be social obstacles to implementing this technique in agricultural landscapes, such as perceptions that the land is not being used productively.
Applied nucleation is likely to be most effective in cases where: planted vegetation nuclei enhance seed dispersal and seedling establishment of other species; the spread of nuclei is not strongly inhibited by abiotic or biotic factors; and the approach is compatible with restoration goals and landowner preferences.
Synthesis and applications. Results from our 15‐year, multi‐site study show that applied nucleation can be a cost‐effective strategy for facilitating tropical forest regeneration that holds promise for helping to meet large‐scale international forest restoration commitments.
Resumen
La nucleación aplicada, basada principalmente en la plantación de islas arbóreas, se ha propuesto como una estrategia económica para cumplir con ambiciosos objetivos mundiales de restauración de bosques y paisajes.
Resumimos los resultados de un estudio de 15 años, replicado en 15 sitios en el sur de Costa Rica, que compara la nucleación aplicada con la regeneración natural y las plantaciones de árboles de especies mixtas como estrategias para restaurar el bosque tropical. Hemos recolectado datos sobre la supervivencia y el crecimiento de los árboles plantados, el reclutamiento y la estructura de la vegetación leñosa, la lluvia de semillas, la caída de hojarasca, las epífitas, las aves, los murciélagos y los artrópodos de la hojarasca.
Nuestros resultados indican que las estrategias de restauración utilizando la nucleación aplicada y plantaciones son igualmente efectivas para mejorar la recuperación de la mayoría de los grupos florales y faunísticos, la estructura de la vegetación y las funciones del ecosistema, en comparación con la regeneración natural.
La dispersión de semillas y el reclutamiento leñoso son mayores en los tratamientos de nucleación aplicada y de plantación que en los tratamientos de regeneración natural; la cobertura del dosel ha aumentado sustancialmente tanto en la regeneración natural como en los tratamientos de nucleación aplicadas; y la mortalidad de las especies arbóreas fijadores de N plantadas ha aumentado en los últimos años. Estas tendencias han llevado a cambios rápidos en la composición y estructura de la vegetación y el ciclo de nutrientes.
La estrategia de nucleación aplicada es más barata que las plantaciones de árboles de especies mixtas, pero pueden existir obstáculos sociales para implementar esta técnica en paisajes agrícolas, como la percepción que la tierra no se está utilizando productivamente.
Es probable que la nucleación aplicada sea más efectiva en los casos en que: los núcleos de vegetación plantados mejoran la dispersión de semillas y el establecimiento de plántulas de otras especies; la propagación de los núcleos no está fuertemente inhibida por factores abióticos o bióticos; y el enfoque es compatible con los objetivos de restauración y las preferencias de los propietarios.
Síntesis y aplicaciones. Resultados de nuestro estudio muestran que la nucleación aplicada puede ser una estrategia económica para facilitar la regeneración forestal que promete ayudar a cumplir los compromisos internacionales de restauración forestal a gran escala.
Results from our 15‐year, multi‐site study show that applied nucleation can be a cost‐effective strategy for facilitating tropical forest regeneration that holds promise for helping to meet large‐scale international forest restoration commitments. (Artist credit: Michelle Pastor)
Nematodes are important parasites of people and animals, and in natural ecosystems they are a major ecological force. Strongyloides ratti is a common parasitic nematode of wild rats and we have ...investigated its population genetics using single-worm, whole-genome sequencing. We find that S. ratti populations in the UK consist of mixtures of mainly asexual lineages that are widely dispersed across a host population. These parasite lineages are likely very old and may have originated in Asia from where rats originated. Genes that underly the parasitic phase of the parasite's life cycle are hyperdiverse compared with the rest of the genome, and this may allow the parasites to maximise their fitness in a diverse host population. These patterns of parasitic nematode population genetics have not been found before and may also apply to Strongyloides spp. that infect people, which will affect how we should approach their control.
In the phase IV, open-label, single-arm study NCT01203917, first-line gefitinib 250 mg/d was effective and well tolerated in Caucasian patients with epidermal growth factor receptor (EGFR) ...mutation-positive non–small-cell lung cancer (previously published). Here, we report EGFR mutation analyses of plasma-derived, circulating-free tumor DNA.
Mandatory tumor and duplicate plasma (1 and 2) baseline samples were collected (all screened patients; n = 1060). Preplanned, exploratory analyses included EGFR mutation (and subtype) status of tumor versus plasma and between plasma samples. Post hoc, exploratory analyses included efficacy by tumor and plasma EGFR mutation (and subtype) status.
Available baseline tumor samples were 1033 of 1060 (118 positive of 859 mutation status known; mutation frequency, 13.7%). Available plasma 1 samples were 803 of 1060 (82 positive of 784 mutation status known; mutation frequency, 10.5%). Mutation status concordance between 652 matched tumor and plasma 1 samples was 94.3% (95% confidence interval CI, 92.3–96.0) (comparable for mutation subtypes); test sensitivity was 65.7% (95% CI, 55.8–74.7); and test specificity was 99.8% (95% CI, 99.0–100.0). Twelve patients of unknown tumor mutation status were subsequently identified as plasma mutation-positive. Available plasma 2 samples were 803 of 1060 (65 positive of 224 mutation status-evaluable and -known). Mutation status concordance between 224 matched duplicate plasma 1 and 2 samples was 96.9% (95% CI, 93.7–98.7). Objective response rates are as follows: mutation-positive tumor, 70% (95% CI, 60.5–77.7); mutation-positive tumor and plasma 1, 76.9% (95% CI, 65.4–85.5); and mutation-positive tumor and mutation-negative plasma 1, 59.5% (95% CI, 43.5–73.7). Median progression-free survival (months) was 9.7 (95% CI, 8.5–11.0; 61 events) for mutation-positive tumor and 10.2 (95% CI, 8.5–12.5; 36 events) for mutation-positive tumor and plasma 1.
The high concordance, specificity, and sensitivity demonstrate that EGFR mutation status can be accurately assessed using circulating-free tumor DNA. Although encouraging and suggesting that plasma is a suitable substitute for mutation analysis, tumor tissue should remain the preferred sample type when available.
1. Active forest restoration typically involves planting trees over large areas; this practice is costly, however, and establishing homogeneous plantations may favour the recruitment of a particular ...suite of species and strongly influence the successional trajectory. An alternative approach is to plant nuclei (islands) of trees to simulate the nucleation model of succession and accelerate natural recovery. 2. We evaluated natural tree recruitment over 4 years in a restoration study replicated at eight former pasture sites in the tropical premontane forest zone of southern Costa Rica. At each site, two active restoration strategies were established in 50 × 50 m plots: planting trees throughout, and planting different-sized tree islands (4 × 4, 8 × 8, 12 × 12 m) within the plot. Restoration plots were compared to similar-sized controls undergoing passive restoration. Sites were spread across c. 100 km2 and distributed along a gradient of surrounding forest, allowing us to compare the relative importance of adjacent forest to that of within-site treatment on tree recruitment. 3. Recruitment of animal-dispersed tree species was more than twofold higher in active (μ = 0·45 recruits m-2) as compared to passive restoration; recruitment was equivalent in plantation and island treatments, even though only 20% of the area in island plots was planted originally. The majority of recruits (>90%) represented early successional species (n = 54 species total). 4. Density of animal-dispersed recruits was greater in large (0·80 ± 0·66 m-2) than small (0·28 ± 0·36 m-2) islands and intermediate in medium-sized islands. Seedling recruitment (< 1 m tall) was greater in the interior of islands as compared to plantations, whereas sapling recruitment was similar, suggesting that island interiors may develop greater density of woody recruits as succession proceeds. 5. Surrounding forest cover did not influence density or species richness of recruits among sites, although this factor may become more important over time. 6. Synthesis and applications. Applied nucleation is a promising restoration strategy that can accelerate forest recovery to a similar degree as plantation-style restoration but is more economical. Appropriate island size is on the order of c. 100 m2. Practitioners should consider the methodology as an alternative to large-scale plantings.
Truttaedacnitis truttae is a cucullanid nematode of primarily salmonine fishes. Brown trout (Salmo trutta) in Europe reportedly become parasitized by ingesting lampreys (Lampetra planeri) carrying ...infective larvae. However, our field and laboratory observations suggested that North American specimens of T. truttae have an alternative life cycle. High abundances and potential impact of T. truttae in rainbow trout, Oncorhynchus mykiss, in the Colorado River drainage in Grand Canyon, where there are no lampreys, prompted a study on the transmission dynamics of this nematode. Eggs of T. truttae, collected from live gravid females, were incubated in the laboratory. Snails, Physa gyrina and Lymnaea sp., were exposed to T. truttae larvae 3–4 wk later. Active larvae of T. truttae were observed penetrating the intestinal wall of exposed snails, and worm larvae were found in the visceral tissues when examined 1 wk after exposure. Larvae in snails showed little growth and development 2 wk later and corresponded to L3 larvae. Infected snails were fed to hatchery-reared juvenile rainbow trout. Developing stages were subsequently found in the mucosal lining and lumen of trout intestines. Adult male and female (gravid) worms were found in the ceca of trout examined 5–6 mo after consuming infected snails. Larvae found in pepsin/trypsin digests and mucosal scrapings from wild, naturally infected, trout corroborate laboratory findings. Screening of Physa sp. and gammarids collected from Colorado River, Grand Canyon, for natural infections with T. truttae using the ITS1 rDNA marker gave positive results. Truttaedacnitis truttae is the second species, after Truttaedacnitis clitellarius of lake sturgeon, capable of using a snail first intermediate/paratenic host and is similar to several other cucullanids in having a histotropic phase of development in the definitive fish host.
Body weight is regulated by complex neurohormonal interactions between endocrine signals of long-term adiposity (e.g., leptin, a hypothalamic signal) and short-term satiety (e.g., amylin, a hindbrain ...signal). We report that concurrent peripheral administration of amylin and leptin elicits synergistic, fat-specific weight loss in leptin-resistant, diet-induced obese rats. Weight loss synergy was specific to amylin treatment, compared with other anorexigenic peptides, and dissociable from amylin's effect on food intake. The addition of leptin after amylin pretreatment elicited further weight loss, compared with either monotherapy condition. In a 24-week randomized, double-blind, clinical proof-of-concept study in overweight/obese subjects, coadministration of recombinant human leptin and the amylin analog pramlintide elicited 12.7% mean weight loss, significantly more than was observed with either treatment alone (P < 0.01). In obese rats, amylin pretreatment partially restored hypothalamic leptin signaling (pSTAT3 immunoreactivity) within the ventromedial, but not the arcuate nucleus and up-regulated basal and leptin-stimulated signaling in the hindbrain area postrema. These findings provide both nonclinical and clinical evidence that amylin agonism restored leptin responsiveness in diet-induced obesity, suggesting that integrated neurohormonal approaches to obesity pharmacotherapy may facilitate greater weight loss by harnessing naturally occurring synergies.
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