Membrane Transporter of Serotonin and Hypercholesterolemia in Children.

The serotonin membrane transporter is one of the main mechanisms of plasma serotonin concentration regulation. Serotonin plays an important role in the pathogenesis of various cardiovascular diseases, stimulating the proliferation of smooth muscle cells, key cells in the process of hypertrophic vascular remodeling. Vascular remodeling is one of the leading prognostically unfavorable factors of atherosclerosis, the main manifestation of familial hypercholesterolemia. Familial hypercholesterolemia is one of the most common genetically determined lipid metabolism disorders and occurs in 1 in 313 people. The aim of our study was to investigate the levels of plasma and platelet serotonin, 5-hydroxyindoleacetic acid, and membrane transporter in a cross-sectional study of two pediatric groups, including patients with familial hypercholesterolemia and the control group, which consisted of apparently healthy children without cardiovascular diseases. The study involved 116 children aged 5 to 17 years old. The proportion of boys was 50% (58/116) and the average age of the children was 10.5 years (CI 2.8-18.1). The concentrations of serotonin in blood plasma and platelets and 5-hydroxyindoleacetic acid were higher in children with familial hypercholesterolemia than in the controls. The concentration of the serotonin transporter in platelets in healthy children, compared with the main group, was 1.3 times higher. A positive correlation was revealed between the level of serotonin (5-HT and PWV: ρ = 0.6, p < 0.001), its transporter (SERT and PWV: ρ = 0.5, p < 0.001), and the main indicators of arterial vascular stiffness. Our study revealed the relationship between high serotonin and SERT concentrations and markers of arterial stiffness. The results we obtained suggest the involvement of serotonin and SERT in the process of vascular remodeling in familial hypercholesterolemia in children.

Establishment and management of wildflower areas for insect pollinators in commercial orchards.

Sown wildflower areas are increasingly recommended as an agri-environmental intervention measure, but evidence for their success is limited to particular insect groups or hampered by the challenges of establishing seed mixes and maintaining flower abundance over time. We conducted a replicated experiment to establish wildflower areas to support insect pollinators in apple orchards. Over three years, and across 23 commercial UK orchards with and without sown wildflowers, we conducted 828 transect surveys across various non-crop habitats. We found that the abundance of flower-visiting solitary bees, bumblebees, honeybees, and beetles was increased in sown wildflower areas, compared with existing non-crop habitats in control orchards, from the second year following floral establishment. Abundance of hoverflies and other non-syrphid flies was increased in wildflower areas from the first year. Beyond the effect of wildflower areas, solitary bee abundance was also positively related to levels of floral cover in other local habitats within orchards, but neither local nor wider landscape-scale context affected abundance of other studied insect taxa within study orchards. There was a change in plant community composition on the sown wildflower areas between years, and in patterns of flowering within and between years, showing a succession from unsown weedy species towards a dominance of sown species over time. We discuss how the successful establishment of sown wildflower areas and delivery of benefits for different insect taxa relies on appropriate and reactive management practices as a key component of any such agri-environment scheme.

First direct measurements of behavioural responses by Cuvier's beaked whales to mid-frequency active sonar.

Most marine mammal- strandings coincident with naval sonar exercises have involved Cuvier's beaked whales (Ziphius cavirostris). We recorded animal movement and acoustic data on two tagged Ziphius and obtained the first direct measurements of behavioural responses of this species to mid-frequency active (MFA) sonar signals. Each recording included a 30-min playback (one 1.6-s simulated MFA sonar signal repeated every 25 s); one whale was also incidentally exposed to MFA sonar from distant naval exercises. Whales responded strongly to playbacks at low received levels (RLs; 89-127 dB re 1 µPa): after ceasing normal fluking and echolocation, they swam rapidly, silently away, extending both dive duration and subsequent non-foraging interval. Distant sonar exercises (78-106 dB re 1 µPa) did not elicit such responses, suggesting that context may moderate reactions. The observed responses to playback occurred at RLs well below current regulatory thresholds; equivalent responses to operational sonars could elevate stranding risk and reduce foraging efficiency.

Interstitial Lung Disease in Neonates: A Long Road Is Being Paved.

Background: Interstitial lung disease (ILD) is one of the most difficult conditions in pulmonology due to difficulties in diagnosing, classifying, and treating this condition. They require invasive approaches to diagnose (e.g., lung biopsy), non-applicable methods (e.g., lung function tests in newborns), or potentially non-accessible methods (e.g., genetic testing in not-well-equipped facilities, and several weeks are required for results to be announced). They represent a heterogeneous group of diseases in which the alveolar epithelium, parenchyma, and capillaries of the lungs are damaged, which leads to changes in the pulmonary interstitium, proliferation of connective tissue, and thickening of the alveolar-capillary membranes and alveolar septa. These changes are accompanied by impaired oxygen diffusion, progressive respiratory failure, and radiographic signs of bilateral dissemination. Although adult and child classifications for ILD have evolved over the years, classification for ILD in neonates remains a challenge. Case presentation: Here we discuss ILD in neonates briefly, and report two rare cases of ILD (a male white neonate, two-day-old with fibrosing alveolitis, and another male white neonate, one-day old with desquamative interstitial pneumonitis), with these diagnoses initially thought to be presented only in adulthood. Lung biopsy and histopathological findings of the two neonates have shown mononuclear cells in the alveolar spaces, and thickening of the alveolar walls confirmed the diagnosis of fibrosing alveolitis in one neonate, and desquamation of the large mononuclear cells in the intra-alveolar space in the other neonate, with the diagnosis of desquamative interstitial pneumonitis being confirmed. Interstitial lung disease lacks a consensus guideline on classification and diagnosis in neonates, rendering it one of the greatest challenges to pediatricians and neonatologists with remarkable morbidity and mortality rates. Conclusions: Fibrosing alveolitis and desquamative interstitial pneumonitis (DIP) are not adult-only conditions, although rare in neonates, histopathological examination and clinical practice can confirm the diagnosis. Based on our clinical practice, prenatal and maternal conditions may serve as potential risk factors for developing IDL in neonates, and further studies are needed to prove this hypothesis.

Phenotypic continuum of NFU1-related disorders.

Bi-allelic variants in Iron-Sulfur Cluster Scaffold (NFU1) have previously been associated with multiple mitochondrial dysfunctions syndrome 1 (MMDS1) characterized by early-onset rapidly fatal leukoencephalopathy. We report 19 affected individuals from 10 independent families with ultra-rare bi-allelic NFU1 missense variants associated with a spectrum of early-onset pure to complex hereditary spastic paraplegia (HSP) phenotype with a longer survival (16/19) on one end and neurodevelopmental delay with severe hypotonia (3/19) on the other. Reversible or irreversible neurological decompensation after a febrile illness was common in the cohort, and there were invariable white matter abnormalities on neuroimaging. The study suggests that MMDS1 and HSP could be the two ends of the NFU1-related phenotypic continuum.

COVID-19, Acute Lymphoblastic Leukemia, and Down Syndrome: A Short Review and a Case Report.

SARS-CoV-2 which causes COVID-19 has been a great challenge to treat and deal with; despite strict measures that had been implemented by governments and organizations, worrying rates of morbidity and mortality are still being reported. Although available data have expressed that moderate or even mild forms of the disease are expected amongst most pediatrics cases, minimal data are available on the prognosis and the disease's complications on the immunocompromised, especially oncology patients. We report a case of relapsed precursor B-cell acute lymphoblastic leukemia of a child with Down syndrome and COVID-19 and outline the treatment regimen that we used.

Data quantity is more important than its spatial bias for predictive species distribution modelling.

Biological records are often the data of choice for training predictive species distribution models (SDMs), but spatial sampling bias is pervasive in biological records data at multiple spatial scales and is thought to impair the performance of SDMs. We simulated presences and absences of virtual species as well as the process of recording these species to evaluate the effect on species distribution model prediction performance of (1) spatial bias in training data, (2) sample size (the average number of observations per species), and (3) the choice of species distribution modelling method. Our approach is novel in quantifying and applying real-world spatial sampling biases to simulated data. Spatial bias in training data decreased species distribution model prediction performance, but sample size and the choice of modelling method were more important than spatial bias in determining the prediction performance of species distribution models.

Quantifying large-scale ecosystem stability with remote sensing data.

To fully understand ecosystem functioning under global change, we need to be able to measure the stability of ecosystem functioning at multiple spatial scales. Although a number of stability components have been established at small spatial scales, there has been little progress in scaling these measures up to the landscape. Remote sensing data holds huge potential for studying processes at landscape scales but requires quantitative measures that are comparable from experimental field data to satellite remote sensing. Here we present a methodology to extract four components of ecosystem functioning stability from satellite-derived time series of Enhanced Vegetation Index (EVI) data. The four stability components are as follows: variability, resistance, recovery time and recovery rate in ecosystem functioning. We apply our method to the island of Ireland to demonstrate the use of remotely sensed data to identify large disturbance events in productivity. Our method uses stability measures that have been established at the field-plot scale to quantify the stability of ecosystem functioning. This makes our method consistent with previous small-scale stability research, whilst dealing with the unique challenges of using remotely sensed data including noise. We encourage the use of remotely-sensed data in assessing the stability of ecosystems at a scale that is relevant to conservation and management practices.

Ecological costs of climate change on marine predator-prey population distributions by 2050.

Identifying and quantifying the effects of climate change that alter the habitat overlap of marine predators and their prey population distributions is of great importance for the sustainable management of populations. This study uses Bayesian joint models with integrated nested Laplace approximation (INLA) to predict future spatial density distributions in the form of common spatial trends of predator-prey overlap in 2050 under the "business-as-usual, worst-case" climate change scenario. This was done for combinations of six mobile marine predator species (gray seal, harbor seal, harbor porpoise, common guillemot, black-legged kittiwake, and northern gannet) and two of their common prey species (herring and sandeels). A range of five explanatory variables that cover both physical and biological aspects of critical marine habitat were used as follows: bottom temperature, stratification, depth-averaged speed, net primary production, and maximum subsurface chlorophyll. Four different methods were explored to quantify relative ecological cost/benefits of climate change to the common spatial trends of predator-prey density distributions. All but one future joint model showed significant decreases in overall spatial percentage change. The most dramatic loss in predator-prey population overlap was shown by harbor seals with large declines in the common spatial trend for both prey species. On the positive side, both gannets and guillemots are projected to have localized regions with increased overlap with sandeels. Most joint predator-prey models showed large changes in centroid location, however the direction of change in centroids was not simply northwards, but mostly ranged from northwest to northeast. This approach can be very useful in informing the design of spatial management policies under climate change by using the potential differences in ecological costs to weigh up the trade-offs in decisions involving issues of large-scale spatial use of our oceans, such as marine protected areas, commercial fishing, and large-scale marine renewable developments.

Land cover drives large scale productivity-diversity relationships in Irish vascular plants.

The impact of productivity on species diversity is often studied at small spatial scales and without taking additional environmental factors into account. Focusing on small spatial scales removes important regional scale effects, such as the role of land cover heterogeneity. Here, we use a regional spatial scale (10 km square) to establish the relationship between productivity and vascular plant species richness across the island of Ireland that takes into account variation in land cover. We used generalized additive mixed effects models to relate species richness, estimated from biological records, to plant productivity. Productivity was quantified by the satellite-derived enhanced vegetation index. The productivity-diversity relationship was fitted for three land cover types: pasture-dominated, heterogeneous, and non-pasture-dominated landscapes. We find that species richness decreases with increasing productivity, especially at higher productivity levels. This decreasing relationship appears to be driven by pasture-dominated areas. The relationship between species richness and heterogeneity in productivity (both spatial and temporal) varies with land cover. Our results suggest that the impact of pasture on species richness extends beyond field level. The effect of human modified landscapes, therefore, is important to consider when investigating classical ecological relationships, particularly at the wider landscape scale.

Parkinson's Disease in Central Asian and Transcaucasian Countries: A Review of Epidemiology, Genetics, Clinical Characteristics, and Access to Care.

Our understanding of Parkinson's disease (PD) has significantly accelerated over the last few years, but predominant advances have been made in developed, Western countries. Little is known about PD in the Central Asian (CA) and Transcaucasian (TC) countries. Here, we review the clinical characteristics, treatments used, epidemiology, and genetics of PD in CA and TC countries via a methodological search in MEDLINE, EMBASE, Scopus, Web of Science, and Google Scholar databases. For the acquisition of PD care-related data, the search was extended to the local web resources. Our findings showed that PD prevalence in the region is averaging 62 per 100,000 population. The mean age of onset is 56.4 ± 2.8 in females and 63.3 ± 3.5 in males. Large-scale national studies on PD prevalence from the region are currently lacking. A limited number of genetic studies with small cohorts and inconclusive results were identified. The G2019S LRRK2 mutation, the commonest mutation in PD worldwide, was found in 5.7% of patients with idiopathic PD and 17.6% of familial cases in 153 Uzbek patients. Our review highlighted systematic deficiencies in PD health care in the region including lacks of neurologists specializing in PD, delays in PD diagnosis, absence of specialized PD nurses and PD rehab services, limited access to PD medications and surgery, and the unavailability of PD infusion therapies. Overall, this article demonstrated the paucity of data on this common neurological disorder in CA and TC countries and identified a number of healthcare areas that require an urgent consideration. We conclude that well-designed large-scale epidemiological, genetic, and clinical studies are desperately needed in this region. Healthcare professionals, local and national institutions, and stakeholders must come together to address deficiencies in PD healthcare systems in CA and TC countries.

Assessing the importance of self-regulating mechanisms in diamondback moth population dynamics: application of discrete mathematical models.

The applicability of discrete mathematical models for the description of diamondback moth (DBM) (Plutella xylostella L.) population dynamics was investigated. The parameter values for several well-known discrete time models (Skellam, Moran-Ricker, Hassell, Maynard Smith-Slatkin, and discrete logistic models) were estimated for an experimental time series from a highland cabbage-growing area in eastern Kenya. For all sets of parameters, boundaries of confidence domains were determined. Maximum calculated birth rates varied between 1.086 and 1.359 when empirical values were used for parameter estimation. After fitting of the models to the empirical trajectory, all birth rate values resulted considerably higher (1.742-3.526). The carrying capacity was determined between 13.0 and 39.9DBM/plant, after fitting of the models these values declined to 6.48-9.3, all values well within the range encountered empirically. The application of the Durbin-Watson criteria for comparison of theoretical and experimental population trajectories produced negative correlations with all models. A test of residual value groupings for randomness showed that their distribution is non-stochastic. In consequence, we conclude that DBM dynamics cannot be explained as a result of intra-population self-regulative mechanisms only (=by any of the models tested) and that more comprehensive models are required for the explanation of DBM population dynamics.

Endothelin-1, nitric oxide, serotonin and high blood pressure in male adolescents.

BACKGROUND: Essential arterial hypertension (EAH) in adolescents represents a social burden. The endothelium is involved in the pathogenesis of EAH. Imbalance of key vasoactive factors - namely nitric oxide (NO) and endothelin-1 (ET-1) - is observed, and serotonin (5-HT) release is also impaired. The relationship between the factors and high blood pressure (BP) has been established mainly in preclinical studies and in the adult age. The aim of the present manuscript is to establish the association between plasma ET-1, serum NO and 5-HT, platelet 5-HT levels and BP in male adolescents, analyzing their concentrations in controls, prehypertensive and hypertensive children. Consequently, we want to evaluate ET-1, NO and 5-HT levels as preclinical biomarkers of EAH. METHODS: Outpatient adolescents, examined at Children's Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan, were recruited between 26th of May and 25th of September 2016. Predictor variables identified were plasma ET-1, serum NO and 5-HT levels and were evaluated in serum and platelets of case and control groups. RESULTS: Plasma ET-1 and serum 5-HT concentrations in prehypertensive and hypertensive children were higher than in controls, with hypertensive adolescents showing higher levels of both factors compared with prehypertensive adolescents. Platelet 5-HT levels were lower in prehypertensive and hypertensive children compared with controls, while serum NO levels were higher in prehypertensive children than in hypertensive children. CONCLUSION: Measurable ET-1, NO and 5-HT are related to BP in adolescents and may serve as diagnostic biomarkers of EAH. Furthermore, they could help to better define prehypertensive and hypertensive children.

Bayesian joint models with INLA exploring marine mobile predator-prey and competitor species habitat overlap.

Understanding spatial physical habitat selection driven by competition and/or predator-prey interactions of mobile marine species is a fundamental goal of spatial ecology. However, spatial counts or density data for highly mobile animals often (1) include excess zeros, (2) have spatial correlation, and (3) have highly nonlinear relationships with physical habitat variables, which results in the need for complex joint spatial models. In this paper, we test the use of Bayesian hierarchical hurdle and zero-inflated joint models with integrated nested Laplace approximation (INLA), to fit complex joint models to spatial patterns of eight mobile marine species (grey seal, harbor seal, harbor porpoise, common guillemot, black-legged kittiwake, northern gannet, herring, and sandeels). For each joint model, we specified nonlinear smoothed effect of physical habitat covariates and selected either competing species or predator-prey interactions. Out of a range of six ecologically important physical and biologic variables that are predicted to change with climate change and large-scale energy extraction, we identified the most important habitat variables for each species and present the relationships between these bio/physical variables and species distributions. In particular, we found that net primary production played a significant role in determining habitat preferences of all the selected mobile marine species. We have shown that the INLA method is well-suited for modeling spatially correlated data with excessive zeros and is an efficient approach to fit complex joint spatial models with nonlinear effects of covariates. Our approach has demonstrated its ability to define joint habitat selection for both competing and prey-predator species that can be relevant to numerous issues in the management and conservation of mobile marine species.