Properties of small molecular drug loading and diffusion in a fluorinated PEG hydrogel studied by ^1H molecular diffusion NMR and ^(19)F spin diffusion NMR

R_f-PEG (fluoroalkyl double-ended poly(ethylene glycol)) hydrogel is potentially useful as a drug delivery depot due to its advanced properties of sol–gel two-phase coexistence and low surface erosion. In this study, ^1H molecular diffusion nuclear magnetic resonance (NMR) and ^(19)F spin diffusion NMR were used to probe the drug loading and diffusion properties of the R_f-PEG hydrogel for small anticancer drugs, 5-fluorouracil (FU) and its hydrophobic analog, 1,3-dimethyl-5-fluorouracil (DMFU). It was found that FU has a larger apparent diffusion coefficient than that of DMFU, and the diffusion of the latter was more hindered. The result of ^(19)F spin diffusion NMR for the corresponding freeze-dried samples indicates that a larger portion of DMFU resided in the R_f core/IPDU intermediate-layer region (where IPDU refers to isophorone diurethane, as a linker to interconnect the R_f group and the PEG chain) than that of FU while the opposite is true in the PEG–water phase. To understand the experimental data, a diffusion model was proposed to include: (1) hindered diffusion of the drug molecules in the R_f core/IPDU-intermediate-layer region; (2) relatively free diffusion of the drug molecules in the PEG-water phase (or region); and (3) diffusive exchange of the probe molecules between the above two regions. This study also shows that molecular diffusion NMR combined with spin diffusion NMR is useful in studying the drug loading and diffusion properties in hydrogels for the purpose of drug delivery applications

The TMS Map Scales with Increased Stimulation Intensity and Muscle Activation

One way to study cortical organisation, or its reorganisation, is to use transcranial magnetic stimulation (TMS) to construct a map of corticospinal excitability. TMS maps are reported to be acquired with a wide variety of stimulation intensities and levels of muscle activation. Whilst MEPs are known to increase both with stimulation intensity and muscle activation, it remains to be established what the effect of these factors is on the map's centre of gravity (COG), area, volume and shape. Therefore, the objective of this study was to systematically examine the effect of stimulation intensity and muscle activation on these four key map outcome measures. In a first experiment, maps were acquired with a stimulation intensity of 110, 120 and 130% of resting threshold. In a second experiment, maps were acquired at rest and at 5, 10, 20 and 40% of maximum voluntary contraction. Map area and map volume increased with both stimulation intensity (P 0.09 in all cases). This result indicates the map simply scales with stimulation intensity and muscle activation

Validation of the SF-36 in patients with endometriosis.

OBJECTIVES: Endometriosis presents with significant pain as the most common symptom. Generic health measures can allow comparisons across diseases or populations. However, the Medical Outcomes Study Short Form 36 (SF-36) has not been validated for this disease. The goal of this study was to validate the SF-36 (version 2) for endometriosis. METHODS: Using data from two clinical trials (N = 252 and 198) of treatment for endometriosis, a full complement of psychometric analyses was performed. Additional instruments included a pain visual analog scale (VAS); a physician-completed questionnaire based on patient interview (modified Biberoglu and Behrman--B&B); clinical global impression of change (CGI-C); and patient satisfaction with treatment. RESULTS: Bodily pain (BP) and the Physical Component Summary Score (PCS) were correlated with the pain VAS at baseline and over time and the B&B at baseline and end of study. In addition, those who had the greatest change in BP and PCS also reported the greatest change on CGI-C and patient satisfaction with treatment. Other subscales showed smaller, but significant, correlations with change in the pain VAS, CGI-C, and patient satisfaction with treatment. CONCLUSIONS: The SF-36--particularly BP and the PCS--appears to be a valid and responsive measure for endometriosis and its treatment

Major life events as predictors of loneliness in adolescence

© 2015, Springer Science+Business Media New York. The present study investigates the validity of early major life events as predictors of loneliness among 978 high-school students. A cross-sectional research design was utilized to examine the relationship between latent classes of six major life events and feelings of family-related and peer-related loneliness. Latent class analysis revealed three distinct event typologies: a normative group, a mover and divorce group, and a loss and illness group. Subsequent logistic regression revealed that membership of the movers and divorce group was associated with family-related loneliness, but not with peer-related loneliness. Membership of the loss and illness group was not associated with family-related or peer-related loneliness. The study lends some support to theoretical approaches that associate loneliness with major life events. However, the mixed study results underscore the relevance of investigating a spectrum of life events and distinguishing between different sources of loneliness.status: publishe

MAMMALS IN PORTUGAL: A data set of terrestrial, volant, and marine mammal occurrences in Portugal

Mammals are threatened worldwide, with ca. 26% of all species being included in the IUCN threatened categories. This overall pattern is primarily associated to habitat loss or degradation, and human persecution for terrestrial mammals, and pollution, open net fishing, climate change and prey depletion for marine mammals. Mammals play a key role in maintaining ecosystems functionality and resilience, and therefore information on their distribution is crucial to delineate and support conservation actions. MAMMALS IN PORTUGAL is a publicly available data set compiling unpublished geo-referenced occurrence records of 92 terrestrial, volant, and marine mammals in mainland Portugal and archipelagos of Azores and Madeira that includes 107,852 data entries between 1873 and 2021 (72% of the data occurring in 2000 and 2021). The methods used to collect the data were: live observations/captures (42%), sign surveys (38%), camera trapping (16%), bioacoustics surveys (4%) and radio-tracking and inquiries that represent less than 1% of the records. The data set includes 13 types of records: 1) burrows | soil mounds | tunnel, 2) capture, 3) colony, 4) dead animal | hair | skulls | jaws, 5) genetic confirmation, 6) inquiries, 7) observation of live animal, 8), observation in shelters, 9) photo trapping | video, 10), predators diet | pellets | pine cones/nuts, 11) scat | track | ditch, 12) telemetry and 13) vocalization | echolocation. The spatial uncertainty of most records ranges between 0 and 100 m (76%). Rodentia (n = 34,754) has the highest number of records followed by Chiroptera (n = 18,858), Carnivora (n = 18,594), Lagomorpha (n = 17,679), Cetartiodactyla (n = 11,568) and Eulipotyphla (n = 6400). The data set includes records of species classified by the IUCN as threatened (e.g., Oryctolagus cuniculus (n = 12,407), Monachus monachus (n = 1512), and Lynx pardinus (n = 197)]. We believe that this data set may stimulate the publication of other European countries data sets which would certainly contribute to ecology and conservation-related research, and therefore assisting on the development of more accurate and tailored conservation management strategies for each species. There are no copyright restrictions; please cite this data paper when the data are used in publications

Increasing vegetable intakes: rationale and systematic review of published interventions

Purpose While the health benefits of a high fruit and vegetable consumption are well known and considerable work has attempted to improve intakes, increasing evidence also recognises a distinction between fruit and vegetables, both in their impacts on health and in consumption patterns. Increasing work suggests health benefits from a high consumption specifically of vegetables, yet intakes remain low, and barriers to increasing intakes are prevalent making intervention difficult. A systematic review was undertaken to identify from the published literature all studies reporting an intervention to increase intakes of vegetables as a distinct food group. Methods Databases—PubMed, PsychInfo and Medline—were searched over all years of records until April 2015 using pre-specified terms. Results Our searches identified 77 studies, detailing 140 interventions, of which 133 (81 %) interventions were conducted in children. Interventions aimed to use or change hedonic factors, such as taste, liking and familiarity (n = 72), use or change environmental factors (n = 39), use or change cognitive factors (n = 19), or a combination of strategies (n = 10). Increased vegetable acceptance, selection and/or consumption were reported to some degree in 116 (83 %) interventions, but the majority of effects seem small and inconsistent. Conclusions Greater percent success is currently found from environmental, educational and multi-component interventions, but publication bias is likely, and long-term effects and cost-effectiveness are rarely considered. A focus on long-term benefits and sustained behaviour change is required. Certain population groups are also noticeably absent from the current list of tried interventions

Road verges as habitat for the Cabrera vole: a vegetation analysis

The Cabrera vole (Microtus cabrerae Thomas 1906) is a threatened rodent showing a fragmented distribution in the Iberian Peninsula. Although specific microhabitat requirements have been pointed out for the species, road verges are sometimes occupied. The aim of this study is the identification and comparison of the floristic composition between road verge and meadow colonies. Vegetation was sampled in 26 colonies in five geographical areas. Cover of herbaceous stratum was sampled in plots of 1x1 m. Several variables related to plant diversity, Raunkiaer life-forms, taxonomic groups, disturbance and soil properties were measured. Data analysis was undertaken with Mann-Whitney tests and ordination techniques (DCA and CCA). Road verge and meadow colonies of Cabrera vole showed differentiated herbaceous vegetation composition. Indicator species of road verge colonies corresponded mainly to annual grasses and forbs, ruderal and nitrophilous species, along with a few perennials. In meadows, perennial grasses and moisture indicative species were more common. Although road verges showed higher diversity in the most usually consumed grasses in the vole’s diet, they suggested several disadvantages as habitat, such as higher disturbance, lower moisture availability during summer and reduced colony surface

Distribution of alien tetrapods in the Iberian Peninsula

We present a dataset that assembles occurrence records of alien tetrapods (amphibians, reptiles, birds and mammals) in the Iberian Peninsula, a coherent biogeographically unit where introductions of alien species have occurred for millennia. These data have important potential applications for ecological research and management, including the assessment of invasion risks, formulation of preventive and management plans, and research at the biological community level on alien species. This dataset summarizes inventories and data sources on the taxonomy and distribution of alien tetrapods in the Iberia Peninsula, comprising known locations from published literature, expert knowledge and citizen science platforms. An expert-based assessment process allowed the identification of unreliable records (misclassification or natural dispersion from native range), and the classification of species according to their status of reproduction in the wild. Distributional data was harmonized into a common area unit, the 10 × 10 km Universal Transverse Mercator (UTM) system (n = 6,152 cells). The year of observation and/or year of publication were also assigned to the records. In total, we assembled 35,940 unique distribution records (UTM × species × Year) for 253 species (6 amphibians, 16 reptiles, 218 birds and 13 mammals), spanning between 1912 and 2020. The species with highest number of distribution records were the Mediterranean painted frog Discoglossus pictus (n = 59 UTM), the pond slider Trachemys scripta (n = 471), the common waxbill Estrilda astrild (n = 1,275) and the house mouse Mus musculus (n = 4,043), for amphibians, reptiles, birds and mammals, respectively. Most alien species recorded are native to Africa (33%), followed by South America (21%), Asia (19%), North America (12%) and Oceania (10%). Thirty-six species are classified by IUCN as threatened in their native range, namely 2 Critically Endangered (CR), 6 Endangered (EN), 8 Vulnerable (VU), and 20 species Near Threatened (NT). Species maps are provided in DataSet1, as well R code and GIS layers to update them as new records are obtained

Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders

Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease.

International audienceRecently, several genome wide association studies (GWAS) have led to the discovery of 9 new loci of genetic susceptibility in Alzheimer's disease (AD). However, the landscape of the AD genetic susceptibility is far away to be complete and in addition to single-SNP analyses as performed in conventional GWAS, complementary strategies need to be applied to overcome limitations inherent to this type of approaches.. We performed a genome wide haplotype association (GWHA) study in the EADI1 study (n=2,025 AD cases and 5,328 controls) by applying a sliding-windows approach. After exclusion of loci already known to be involved in AD (APOE, BIN1 and CR1), 91 regions with suggestive haplotype effects were identified. In a second step, we attempted to replicate the best suggestive haplotype associations in the GERAD1 consortium (2,820 AD cases and 6,356 controls) and observed that 9 of them showed nominal association. In a third step, we tested relevant haplotype associations in a combined analysis of five additional case-control studies (5,093 AD cases and 4,061 controls). We consistently replicated the association of a haplotype within FRMD4A on Chr.10p13 in all the data set analysed (OR=1.68, 95% CI 1.43- 1.96; p=1.1x10-10). We finally searched for association between SNPs within the FRMD4A locus and Ab plasma concentrations in three independent non demented populations (n=2,579). We reported that polymorphisms were associated with plasma Ab42/Ab40 ratio (best signal, p=5.4x10-7). In conclusion, combining both GWHA study and a conservative three-stage replication approach, we characterised FRMD4A as a new genetic risk factor of AD