Synthesis and evaluation of temperature- and glucose-sensitive nanoparticles based on phenylboronic acid and N-vinylcaprolactam for insulin delivery

Poly N-vinylcaprolactam-co-acrylamidophenylboronic acid p(NVCL-co-AAPBA) was prepared from N-vinylcaprolactam (NVCL) and 3-acrylamidophenylboronic acid (AAPBA), using 2,2-azobisisobutyronitrile (AIBN) as initiator. The synthesis and structure of the polymer were examined by Fourier Transform infrared spectroscopy (FT-IR) and 1H-NMR. Dynamic light scattering (DLS), lower critical solution temperature (LCST) and transmission electron microscopy (TEM) were utilized to characterize the nanoparticles, CD spectroscopy was used to determine if there were any changes to the conformation of the insulin, and cell and animal toxicity were also investigated. The prepared nanoparticles were found to be monodisperse submicron particles and were glucose- and temperature-sensitive. In addition, the nanoparticles have good insulin-loading characteristics, do not affect the conformation of the insulin and show low-toxicity to cells and animals. These p(NVCL-co-AAPBA) nanoparticles may have some value for insulin or other hypoglycemic protein delivery.

The importance of improving diet in 'Securing Scotland's Health': exploring differences in dietary intake between Scotland and England

Background: Various factors have been investigated to account for the higher premature death rates in Scotland compared to England. Higher levels of deprivation in Scotland provide a partial explanation for these differences but recent work comparing areas of the UK with similar deprivation profiles and low life expectancy has shown that this is not the only reason. One hypothesis yet to be tested adequately is differences in diet and nutrition. Objective: To conduct a comparative analysis of dietary intake between Scotland and England using pooled food purchase data from the Living Costs and Food Survey (LCFS) from 2001 to 2012 and to assess differences in equivalised income quintiles (controlling for survey year, age of household reference person, and age household reference person left full-time education). Results: Lower intakes of fruit and vegetables, oil rich fish, fibre, vitamin A, folate, vitamin C and vitamin D and higher intakes of red and processed meat, whole milk, butter, savoury snacks, confectionary, soft drinks, saturated fat and NMES (added sugar and sugar in fruit juice), sodium and alcohol were found for Scotland compared to England. Differences between Scotland and England were higher for those on lower incomes for dietary components known to be related to health outcomes. For example fruit consumption was 14g/day lower for the lowest income quintile compared to 4 g/day lower in the highest quintile for Scotland versus England. Conclusions: A poorer diet in Scotland compared to England, particularly among disadvantaged groups, is likely to be one of the reasons for excess mortality. The current evidence on the continued poor diet in Scotland, particularly in disadvantaged groups, should not be ignored. Identifying effective, culturally appropriate approaches to improve diet across the population and notably in the most deprived areas needs further investment. Funded by NHS Health Scotland. Data provided by DEFRA, ONS and the UK Data Archive.

Setting the agenda for dental education in Scotland: a priority setting exercise including multiple stakehiolders

Introduction The Scottish Oral Health Research Collaboration identified dental education research (DER) as a key strand of their strategy,(1) leading to the formation of the Dental Education Research Group. The starting point for this group was to understand various stakeholders’ perceptions of research priorities, yet no existing studies were found. The aim of the current study was to identify DER priorities for Scotland in the next 3-5 years. Methods The study utilised a similar methodology to that of Dennis et al,(2) in medical education. Data were collected sequentially using two online questionnaires with multiple dental stakeholders represented at undergraduate and postgraduate levels across urban and rural Scotland. 85 participants completed questionnaire 1 (qualitative) and 649 participants completed questionnaire 2 (quantitative). Qualitative and quantitative data analysis approaches were used. Results Of the 24 priorities identified, the top priorities were: role of assessments in identifying competence; undergraduate curriculum prepares for practice; and promoting teamwork within the dental team. Following factor analysis, the priorities loaded on four factors: teamwork and professionalism, measuring and enhancing performance, personal and professional development challenges, and curriculum integration and innovation. The top barriers were lack of time, funding, staff motivation, valuing of DER, and resources/ infrastructure. Discussion There were many similarities between the identified priorities for dental and medical education research2, but also some notable differences, which will be discussed. Overwhelmingly, the identified priorities in dentistry related to fitness for practice and robust assessment practices. Take home message Priority setting exercises with multiple stakeholders are an important first step in developing a national research strategy. References 1. Bagg J, Macpherson L, Mossey P, Rennie J, Saunders B, Taylor M (2010) Strategy for Oral Health Research in Scotland. Edinburgh: The Scottish Government. 2. Dennis A A, Cleland J A, Johnston P, Ker JS, Lough, M Rees CE (2014) Exploring stakeholders’ views of medical education research priorities: a national study. Medical Education, 48(11): 1078-1091.

‘Complementary & alternative medicine’ (CAM): ethical and policy issues

Editorial for Bioethics 2016. 30:(2)

Depolarization of sperm membrane potential is a common feature of men with subfertility and is associated with low fertilization rate at IVF

STUDY QUESTION. Are significant abnormalities in outward (K+) conductance and resting membrane potential (Vm) present in the spermatozoa of patients undertaking IVF and ICSI and if so, what is their functional effect on fertilization success? SUMMARY ANSWER. Negligible outward conductance (≈5% of patients) or an enhanced inward conductance (≈4% of patients), both of which caused depolarization of Vm, were associated with a low rate of fertilization following IVF. WHAT IS KNOWN ALREADY. Sperm-specific potassium channel knockout mice are infertile with defects in sperm function, suggesting that these channels are essential for fertility. These observations suggest that malfunction of K+ channels in human spermatozoa might contribute significantly to the occurrence of subfertility in men. However, remarkably little is known of the nature of K+ channels in human spermatozoa or the incidence and functional consequences of K+ channel defects. STUDY DESIGN, SIZE AND DURATION. Spermatozoa were obtained from healthy volunteer research donors and subfertile IVF and ICSI patients attending a hospital assisted reproductive techniques clinic between May 2013 and December 2015. In total, 40 IVF patients, 41 ICSI patients and 26 normozoospermic donors took part in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS. Samples were examined using electrophysiology (whole-cell patch clamping). Where abnormal electrophysiological characteristics were identified, spermatozoa were further examined for Ca2+ influx induced by progesterone and penetration into viscous media if sufficient sample was available. Full exome sequencing was performed to specifically evaluate potassium calcium-activated channel subfamily M α 1 (KCNMA1), potassium calcium-activated channel subfamily U member 1 (KCNU1) and leucine-rich repeat containing 52 (LRRC52) genes and others associated with K+ signalling. In IVF patients, comparison with fertilization rates was done to assess the functional significance of the electrophysiological abnormalities. MAIN RESULTS AND THE ROLE OF CHANCE. Patch clamp electrophysiology was used to assess outward (K+) conductance and resting membrane potential (Vm) and signalling/motility assays were used to assess functional characteristics of sperm from IVF and ICSI patient samples. The mean Vm and outward membrane conductance in sperm from IVF and ICSI patients were not significantly different from those of control (donor) sperm prepared under the same conditions, but variation between individuals was significantly greater (P< 0.02) with a large number of outliers (>25%). In particular, in ≈10% of patients (7/81), we observed either a negligible outward conductance (4 patients) or an enhanced inward current (3 patients), both of which caused depolarization of Vm. Analysis of clinical data from the IVF patients showed significant association of depolarized Vm (≥0 mV) with low fertilization rate (P= 0.012). Spermatozoa with electrophysiological abnormities (conductance and Vm) responded normally to progesterone with elevation of [Ca2+]i and penetration of viscous medium, indicating retention of cation channel of sperm (CatSper) channel function. LIMITATIONS, REASONS FOR CAUTION. For practical, technical, ethical and logistical reasons, we could not obtain sufficient additional semen samples from men with conductance abnormalities to establish the cause of the conductance defects. Full exome sequencing was only available in two men with conductance defects. WIDER IMPLICATIONS OF THE FINDINGS. These data add significantly to the understanding of the role of ion channels in human sperm function and its impact on male fertility. Impaired potassium channel conductance (Gm) and/or Vm regulation is both common and complex in human spermatozoa and importantly is associated with impaired fertilization capacity when the Vm of cells is completely depolarized.

Optimization of physical and optical properties of biodegradable edible films based on pea starch and guar gum

The influence of process variables (pea starch, guar gum and glycerol) on the viscosity (V), solubility (SOL), moisture content (MC), transparency (TR), Hunter parameters (L, a, and b), total color difference (ΔE), yellowness index (YI), and whiteness index (WI) of the pea starch based edible films was studied using three factors with three level Box–Behnken response surface design. The individual linear effect of pea starch, guar and glycerol was significant (p < 0.05) on all the responses. However, a value was only significantly (p < 0.05) affected by pea starch and guar gum in a positive and negative linear term, respectively. The effect of interaction of starch × glycerol was also significant (p < 0.05) on TR of edible films. Interaction between independent variables starch × guar gum had a significant impact on the b and YI values. The quadratic regression coefficient of pea starch showed a significant effect (p < 0.05) on V, MC, L, b, ΔE, YI, and WI; glycerol level on ΔE and WI; and guar gum on ΔE and SOL value. The results were analyzed by Pareto analysis of variance (ANOVA) and the second order polynomial models were developed from the experimental design with reliable and satisfactory fit with the corresponding experimental data and high coefficient of determination (R2) values (>0.93). Three-dimensional response surface plots were established to investigate the relationship between process variables and the responses. The optimized conditions with the goal of maximizing TR and minimizing SOL, YI and MC were 2.5 g pea starch, 25% glycerol and 0.3 g guar gum. Results revealed that pea starch/guar gum edible films with appropriate physical and optical characteristics can be effectively produced and successfully applied in the food packaging industry.