Lyotropic liquid crystal elastomers for drug delivery

Silicone elastomers like polydimethylsiloxane (PDMS) possess a combination of attractive material and biologicalproperties motivating their widespread use in biomedical applications. Development of elastomers with capacityto deliver active therapeutic substances in the form of drugs is of particular interest to produce medical deviceswith added functionality. In this work, silicone-based lyotropic liquid crystal elastomers with drug-elutingfunctionality were developed using PDMS and triblock copolymer (diacrylated Pluronic F127, DA-F127).Various ternary PDMS–DA-F127–H2O compositions were explored and evaluated. Three compositions werefound to have specific properties of interest and were further investigated for their nanostructure, mechanicalproperties, water retention capacity, and morphology. The ability of the elastomers to encapsulate and releasepolar and nonpolar substances was demonstrated using vancomycin and ibuprofen as model drugs. It was shownthat the materials could deliver both types of drugs with a sustained release profile for up to 6 and 5 days forvancomycin and ibuprofen, respectively. This works demonstrates a lyotropic liquid crystal, silicone-basedelastomer with tailorable mechanical properties, water retention capacity and ability to host and release polarand nonpolar active substances

Non-Holomorphic Ramanujan-type Congruences for Hurwitz Class Numbers

In contrast to all other known Ramanujan-type congruences, we discover that Ramanujan-type congruences for Hurwitz class numbers can be supported on non-holomorphic generating series. We establish a divisibility result for such non-holomorphic congruences of Hurwitz class numbers. The two keys tools in our proof are the holomorphic projection of products of theta series with a Hurwitz class number generating series and a theorem by Serre, which allows us to rule out certain congruences

Inflammation reduces mechanical thresholds in a population of transient receptor potential channel A1-expressing nociceptors in the rat

Inflammatory hypersensitivity is characterized by behavioural reductions in withdrawal thresholds to noxious stimuli. Although cutaneous primary afferent neurones are known to have lowered thermal thresholds in inflammation, whether their mechanical thresholds are altered remains controversial. The transient receptor potential channel A1 (TRPA1) is a receptor localized to putative nociceptive neurones and is implicated in mechanical and thermal nociception. Herein, we examined changes in the properties of single primary afferents in normal and acutely inflamed rats and determined whether specific nociceptive properties, particularly mechanical thresholds, are altered in the subpopulation of afferents that responded to the TRPA1 agonist cinnamaldehyde (TRPA1-positive afferents). TRPA1-positive afferents in normal animals belonged to the mechanonociceptive populations, many of which also responded to heat or capsaicin but only a few of which responded to cold. In acute inflammation, a greater proportion of afferents responded to cinnamaldehyde and an increased proportion of dorsal root ganglion neurones expressed TRPA1 protein. Functionally, in inflammation, TRPA1-positive afferents showed significantly reduced mechanical thresholds and enhanced activity to agonist stimulation. Inflammation altered thermal thresholds in both TRPA1-positive and TRPA1-negative afferents. Our data show that a subset of afferents is sensitized to mechanical stimulation by inflammation and that these afferents are defined by expression of TRPA1

Health-related quality of life and strain in caregivers of Australians with Parkinson’s disease : An observational study

Background: The relationship between health-related quality of life (HRQoL) in people with Parkinson’s disease and their caregivers is little understood and any effects on caregiver strain remain unclear. This paper examines these relationships in an Australian sample. Methods: Using the generic EuroQol (EQ-5D) and disease-specific Parkinson’s Disease Questionnaire-39 Item (PDQ- 39), HRQoL was evaluated in a sample of 97 people with PD and their caregivers. Caregiver strain was assessed using the Modified Caregiver Strain Index. Associations were evaluated between: (i) caregiver and care-recipient HRQoL; (ii) caregiver HRQoL and caregiver strain, and; (iii) between caregiver strain and care-recipient HRQoL. Results: No statistically significant relationships were found between caregiver and care-recipient HRQoL, or between caregiver HRQoL and caregiver strain. Although this Australian sample of caregivers experienced relatively good HRQoL and moderately low strain, a significant correlation was found between HRQoL of people with PD and caregiver strain (rho 0.43, p<.001). Conclusion: Poor HRQoL in people with PD is associated with higher strain in caregivers. Therapy interventions may target problems reported as most troublesome by people with PD, with potential to reduce strain on the caregive

Dietary Essential Amino Acids Affect the Reproduction of the Keystone Herbivore Daphnia pulex

Recent studies have indicated that nitrogen availability can be an important determinant of primary production in freshwater lakes and that herbivore growth can be limited by low dietary nitrogen availability. Furthermore, a lack of specific essential nitrogenous biochemicals (such as essential amino acids) might be another important constraint on the fitness of consumers. This might be of particular importance for cladoceran zooplankton, which can switch between two alternative reproductive strategies – the production of subitaneously developing and resting eggs. Here, we hypothesize that both the somatic growth and the type of reproduction of the aquatic keystone herbivore Daphnia is limited by the availability of specific essential amino acids in the diet. In laboratory experiments, we investigated this hypothesis by feeding a high quality phytoplankton organism (Cryptomonas) and a green alga of moderate nutritional quality (Chlamydomonas) to a clone of Daphnia pulex with and without the addition of essential amino acids. The somatic growth of D. pulex differed between the algae of different nutritional quality, but not dependent on the addition of dissolved amino acids. However, in reproduction experiments, where moderate crowding conditions at saturating food quantities were applied, addition of the essential amino acids arginine and histidine (but not lysine and threonine) increased the total number and the developmental stage of subitaneous eggs. While D. pulex did not produce resting eggs on Cryptomonas, relatively high numbers of resting eggs were released on Chlamydomonas. When arginine and histidine were added to the green algal diet, the production of resting eggs was effectively suppressed. This demonstrates the high, but previously overlooked importance of single essential amino acids for the reproductive strategy of the aquatic keystone herbivore Daphnia

Retinoic Acid Promotes the Generation of Pancreatic Endocrine Progenitor Cells and Their Further Differentiation into β-Cells

The identification of secreted factors that can selectively stimulate the generation of insulin producing β-cells from stem and/or progenitor cells represent a significant step in the development of stem cell-based β-cell replacement therapy. By elucidating the molecular mechanisms that regulate the generation of β-cells during normal pancreatic development such putative factors may be identified. In the mouse, β-cells increase markedly in numbers from embryonic day (e) 14.5 and onwards, but the extra-cellular signal(s) that promotes the selective generation of β-cells at these stages remains to be identified. Here we show that the retinoic acid (RA) synthesizing enzyme Raldh1 is expressed in developing mouse and human pancreas at stages when β-cells are generated. We also provide evidence that RA induces the generation of Ngn3+ endocrine progenitor cells and stimulates their further differentiation into β-cells by activating a program of cell differentiation that recapitulates the normal temporal program of β-cell differentiation

Oxygen Tension Regulates Pancreatic β-Cell Differentiation Through Hypoxia-Inducible Factor 1α

International audienceThese data demonstrate that beta-cell differentiation is controlled by pO2 through HIF1alpha. Modifying pO2 should now be tested in protocols aiming to differentiate beta-cells from embryonic stem cells

Predictors of the psychosocial impact of being a carer of people living with Parkinson’s disease: A systematic review

INTRODUCTION:Caring for a person with Parkinson's disease (PwP) can have a variety of negative consequences that may challenge their ability to continue their caring role. It is still unknown why some individuals adapt better than others in response to such burdens. This review is the first to synthesize and evaluate the evidence on the predictive factors of psychosocial outcomes in PwP carers.METHODS:Studies which identified predictors of psychosocial outcomes for unpaid carers were included. PsychINFO, EMBASE, AMED, BNI and CINAHL databases were searched, supplemented by scanning of references lists of included studies and relevant journals from 2008 onwards. Quality was assessed using the NICE methodology checklist for prognostic studies.RESULTS:Twenty-nine studies were included in the review, providing a low-level of evidence. Carer burden was investigated in 18 studies and mental health and quality of life (QoL) in seven studies each. PwP non-motor symptoms and QoL and carer depression were consistently identified as predictors for at least one psychosocial outcome. Demographics and disease factors were consistently found not to be predictors. Carer involvement and protective factors (e.g. social support, personality) demonstrated promising findings but studies were too few or factors measured inconsistently.CONCLUSION:Confident conclusions could not be drawn regarding the most important predictors that should be targeted in psychosocial interventions due to methodological weaknesses and lack of theoretical testing across the current literature. Future research should build upon psychological theory to gain a better understanding of the mechanisms that explain how carers adapt to caregiving