Aplydactylonins A-C, three new sesquiterpenes from the Vietnamese sea hare Aplysia dactylomela and their cytotoxicity.

Aplydactylonins A-C (1-3), three new sesquiterpenes, were isolated from the Vietnamese sea hare Aplysia dactylomela. Their structures and absolute configurations were elucidated based on spectroscopic analysis, X-ray crystallography, and density functional theory (DFT) calculations of NMR and ECD data. Compound 2 exhibited cytotoxicity against HepG2, DU145 and A549 cells with respective IC50 values of 4.08 ± 0.63, 38.64 ± 1.04 and 12.33 ± 0.95 µM. In addition, HepG2 cells treated with 5 µM compound 2 for 48 h showed a significant increase in early apoptotic cells (P < 0.05) and increased caspase 3 activity (P < 0.01). Moreover, compound 2 induced sub-G1 phase arrest in HepG2 cells.

Support needs of carers making proxy healthcare decisions for people with dementia: a systematic review based on the Noblit and Hare meta-ethnographic synthesis of qualitative studies.

BACKGROUND: There are 50 million dementia sufferers worldwide. Decisions about healthcare often need to be made when the person with dementia lacks capacity to do so.Understanding the support needs of carers acting as proxy healthcare decision-makers will be vital in improving the decision-making process for people with dementia and addressing the holistic needs of carers. OBJECTIVE: The objective of this study was to review the existing literature on the support needs of carers acting as proxy healthcare decision-makers for people with dementia. DESIGN: A qualitative systematic review protocol was published on PROSPERO. The Critical Appraisal Skills Programme checklist was used to appraise study quality. A meta-ethnographic synthesis was performed to develop third-order constructs. DATA SOURCES: A search was conducted using three online databases (MEDLINE, CINAHL and PsycINFO). ELIGIBILITY CRITERIA: Fifteen studies met the inclusion criteria: primary qualitative research involving carers of people with dementia who had been involved in making proxy healthcare decisions. DATA EXTRACTION AND SYNTHESIS: Two independent researchers conducted validity assessments for each paper selected for inclusion, and discrepancies were resolved by discussions with a third reviewer. Nvivo software was used and conceptual findings from study papers lead to interpretations of findings by the team. RESULTS: From the 15 papers included in the study, three main domains arose from the meta-ethnography; informational, practical and emotional. Informational support needs included information about dementia itself and the anticipated disease trajectory. Practical needs included continuity of care, person-centred care and the use of legal frameworks.Emotional support included recognising the guilt that healthcare decisions can provoke and the importance of providing guidance in an empathic manner. CONCLUSIONS: This meta-ethnography highlights opportunities for healthcare professionals and policymakers to improve experiences of carers making proxy healthcare decisions for people with dementia. PROSPERO REGISTRATION NUMBER: CRD42020124485.

"Is it still safe to eat traditional food?" Addressing traditional food safety concerns in aboriginal communities.

Food insecurity is a growing concern for indigenous communities worldwide. While the risk of heavy metal contamination associated to wild food consumption has been extensively studied in the Arctic, data are scarce for the Boreal zone. This study addressed the concerns over possible heavy metal exposure through consumption of traditional food in four Anishnaabeg communities living in the Eastern North American boreal forest. Liver and meat samples were obtained from 196 snowshoe hares (Lepus americanus) trapped during winter 2012 across the traditional lands of the participating communities and within 56-156km of a copper smelter. Interviews were conducted with 78 household heads to assess traditional food habits, focusing on snowshoe hare consumption. Concentrations in most meat and liver samples were below the detection limit for As, Co, Cr, Ni and Pb. Very few meat samples had detectable Cd and Hg concentrations, but liver samples had mean dry weight concentrations of 3.79mg/kg and 0.15mg/kg respectively. Distance and orientation from the smelter did not explain the variability between samples, but percent deciduous and mixed forest cover had a marginal negative effect on liver Cd, Cu and Zn concentrations. The estimated exposition risk from snowshoe hare consumption was low, although heavy consumers could slightly exceed recommended Hg doses. In accordance with the holistic perspective commonly adopted by indigenous people, the nutritional and sociocultural importance of traditional food must be considered in risk assessment. Traditional food plays a significant role in reducing and preventing serious health issues disproportionately affecting First Nations, such as obesity, diabetes, and cardiovascular diseases.

The European Hare (Lepus europaeus): A Picky Herbivore Searching for Plant Parts Rich in Fat.

European hares of both sexes rely on fat reserves, particularly during the reproduc-tive season. Therefore, hares should select dietary plants rich in fat and energy. However, hares also require essential polyunsaturated fatty acids (PUFA) such as linoleic acid (LA) and alpha-linolenic acid (ALA) to reproduce and survive. Although hares are able to absorb PUFA selectively in their gastrointestinal tract, it is unknown whether this mechanism is sufficient to guarantee PUFA supply. Thus, diet selection may involve a trade-off between a preference for energy versus a preference for crucial nutrients, namely PUFA. We compared plant and nutrient availability and use by hares in an arable landscape in Austria over three years. We found that European hares selected their diet for high energy content (crude fat and crude protein), and avoided crude fibre. There was no evidence of a preference for plants rich in LA and ALA. We conclude that fat is the limiting resource for this herbivorous mammal, whereas levels of LA and ALA in forage are sufficiently high to meet daily requirements, especially since their uptake is enhanced by physiological mechanisms. Animals selected several plant taxa all year round, and preferences did not simply correlate with crude fat content. Hence, European hares might not only select for plant taxa rich in fat, but also for high-fat parts of preferred plant taxa. As hares preferred weeds/grasses and various crop types while avoiding cereals, we suggest that promoting heterogeneous habitats with high crop diversity and set-asides may help stop the decline of European hares throughout Europe.

Activity of Selected Antioxidant Enzymes, Selenium Content and Fatty Acid Composition in the Liver of the Brown Hare (Lepus europaeus L.) in Relation to the Season of the Year.

The aim of the study was to evaluate the effect of low concentrations of selenium in the environment on the activity of selected antioxidant enzymes: Se-GSHPx, total GSHPx, SOD, CAT, and GST as well as fatty acid profile in the livers of brown hares during winter and spring. Liver tissues obtained from 20 brown hares collected in the north-eastern Poland in the winter and spring season were analyzed. In the tissue analyzed, a significantly lower level of selenium was noticeable in the spring compared to winter; however, values measured in both seasons indicated a deficiency of this element in the analyzed population of brown hares. There were no differences found that could indicate the influence of Se deficiency on the activity of antioxidant enzymes. The determined activity of antioxidant enzymes and fatty acid composition suggest a negligible impact of the low concentration of Se on the analyzed biochemical parameters of brown hare livers.

Influence of cadmium on metallothionein expression and products of lipid peroxidation in the organs of hares (Lepus europaeus Pallas).

Cadmium occurs naturally in the environment and as an anthropogenic pollutant. Exposure to low concentrations of cadmium is inevitable and may produce toxic effects. Another important aspect of cadmium toxicity is its interaction, often antagonistic, with essential elements such as selenium. The aim of this study was to highlight the risks of long-term exposure to low cadmium concentrations, using a scientific and chemical approach and hares (Lepus europaeus Pallas) as model organisms in a field study. Two study areas were monitored. Levels of cadmium and selenium were quantified in the organs of hares, the expression of metallothioneins I + II and the products of lipid peroxidation were determined. The median cadmium concentrations (wet weight) in the muscle, liver, kidney and brain of hares from an exposed group ranged from 0.033 to 0.037, 0.763 to 1.054, 3.090 to 16.594 and 0.016 to 0.087 µg g(-1), respectively; whereas, the median selenium concentrations (wet weight) ranged from 0.100 to 0.108, 0.153 to 0.332, 0.677 to 0.701 and 0.078 to 0.116 µg g(-1), respectively. Expression of the metallothioneins I + II proteins was observed in tissues. Lipid peroxidation (LPO) levels, measured as malondialdehyde (MDA) equivalents, increased with the cadmium concentration. Further research on long-term exposure to low concentrations of cadmium in the environment is needed.

Ocular tissues and fluids oxidative stress in hares fed on verbascoside supplement.

The influence of a prolonged diet supplemented with the powerful antioxidant verbascoside on the oxidative state of 20 healthy hares eye fluids and tissues has been studied. Verbascoside was dosed at 2, 3, 4 mg/die and the impact on the oxidative state of ocular tissues and fluids was tested by TBARS (thio barbituric acid reactive substances) and TEAC (trolox equivalent antioxidant capacity) assays. The percentage of change in antioxidant activity increased largely in retina and lenses at a daily verbascoside dose of 3 mg, whereas for optic nerve and vitreous humor the higher antioxidant capacity was measured at 4 mg/die verbascoside dose. The present findings demonstrate that verbascoside supplementation is able to protect ocular tissue and fluids from naturally occurring oxidation and that its protective effect depends on the daily dose, being maximum up to 3 mg/die.

Effects of season and reproductive state on lipid intake and fatty acid composition of gastrointestinal tract contents in the European hare.

We investigated lipid content and fatty acid (FA) composition of gastrointestinal tract contents in free-living, herbivorous European hares (Lepus europaeus). Mean crude fat content in hare stomachs and total gastrointestinal (GI) tracts was higher than expected for typical herbivore forages and peaked in late fall when hares massively deposited body fat reserves. Changes of FA proportions in different parts of the GI-tract indicated a highly preferential absorption of polyunsaturated fatty acids (PUFA). A further reduction of PUFA content in the caecum, along with the appearance of odd-chained FAs in caecum, caecotrophes, and colon content, pointed to a biohydrogenation of PUFA in the hare's hindgut. GI-tract contents showed significant seasonal changes in their FA composition. Among PUFA, α-linolenic acid peaked in spring while linoleic acid was predominant in late summer and fall, which probably reflected changes in the plant composition of forage. However, independent of seasonal changes, GI-tracts of lactating females showed a significantly (+33%) higher content of linoleic acid, a FA that is known to increase reproductive performance in European hares. This finding suggests that lactating females actively selected dietary plants rich in linoleic acid, a PUFA that may represent a limited resource for European hares.

Control and eradication of invasive mammals in Great Britain.

This paper provides a 'long view' of the eradication and control of invasive mammals by reviewing the management of 24 mammalian species that have been introduced into Great Britain since the Neolithic period and have subsequently established free-living populations in the wild. The approach provides examples of the issues faced when managing populations and examines some of the lessons that can be learned from successes and failures. The species are covered in the order of introduction, with the control/eradication of rabbit (Oryctolagus cuniculus), muskrat (Ondatra zibethicus), coypu (Myocastor coypus) and American mink (Mustela vison) considered in more detail. The species accounts are set within the context of commitments for the control of invasive alien species made by parties to the Convention on Biological Diversity and guidance provided by the International Union for Conservation of Nature and the Council of Europe. These have led to improvements in the process for assessing risks and co-ordinating action. However, despite some notable cases documented here, there have been few successful eradication programmes carried out in Europe. This paper argues that there is a case for building on the improved frameworks that are being developed in the United Kingdom and elsewhere and for being more ambitious with goals for the management of invasive alien species.

The rise and fall of the mountain hare (Lepus timidus) during Pleistocene glaciations: expansion and retreat with hybridization in the Iberian Peninsula.

The climatic fluctuations during glaciations have affected differently arctic and temperate species. In the northern hemisphere, cooling periods induced the expansion of many arctic species to the south, while temperate species were forced to retract in southern refugia. Consequently, in some areas the alternation of these species set the conditions for competition and eventually hybridization. Hares in the Iberian Peninsula appear to illustrate this phenomenon. Populations of Iberian hare (Lepus granatensis), brown hare (Lepus europaeus) and broom hare (Lepus castroviejoi) in Northern Iberia harbour mitochondrial haplotypes from the mountain hare (Lepus timidus), a mainly boreal and arctic species presently absent from the peninsula. To understand the history of this past introgression we analysed sequence variation and geographical distribution of mitochondrial control region and cytochrome b haplotypes of L. timidus origin found in 378 specimens of these four species. Among 124 L. timidus from the Northern Palaearctic and the Alps we found substantial nucleotide diversity (2.3%) but little differentiation between populations. Based on the mismatch distribution of the L. timidus sequences, this could result from an expansion at a time of temperature decrease favourable to this arctic species. The nucleotide diversity of L. timidus mtDNA found in Iberian L. granatensis, L. europaeus and L. castroviejoi (183, 70 and 1 specimens, respectively) was of the same order as that in L. timidus over its range (1.9%), suggesting repeated introgression of multiple lineages. The structure of the coalescent of L. granatensis sequences indicates that hybridization with L. timidus was followed by expansion of the introgressed haplotypes, as expected during a replacement with competition, and occurred when temperatures started to rise, favouring the temperate species. Whether a similar scenario explains the introgression into Iberian L. europaeus remains unclear but it is possible that it hybridized with already introgressed L. granatensis.

Female reproductive tract abnormalities in European hares (Lepus europaeus) in Australia. philip.stott@adelaide.edu.au.

Populations of European hare (Lepus europaeus) are in decline in Europe, and populations in Australia remain at low densities. Populations are sensitive to size of the breeding stock, which is influenced by fertility in the females. From 1996 to 1999, a total of 272 adult female hares from three Australian populations were dissected and their reproductive systems examined for abnormalities. Cystic endometrial hyperplasia was relatively common and often accompanied by hydrosalpinx. Extrauterine fetuses, neoplasms, pseudopregnancies, and resorptions also were found. However, although pseudopregnancies and resorptions were found in young adults (<12 mo) as well as older hares, conditions possibly causing infertility were almost always in older hares with prevalences up to 46.2%. Only hares with access to known sources of estrogens exhibited pathologic conditions, but sympatric European rabbits (Oryctolagus cuniculus) did not, which is consistent with known difference in responses between the corpora lutea of the two species to exogenous estrogen. Infertility at such a high prevalence could compound and extend the impact of years of low juvenile survival on recruitment.