Rational Development of Stable PYY3-36 Peptide Y2 Receptor Agonists.

PURPOSE: The anorectic effect of PYY3-36 makes it a potential pharmacological weight loss treatment. Modifications of the endogenous peptide to obtain commercially attractive pharmacological and biophysical stability properties are examined. METHODS: Half-life extended PYY3-36 analogues were prepared and examined regarding Y2-receptor potency as well as biophysical and stability properties. RESULTS: Deamidation of asparagine in position 18 and 29 was observed upon incubation at 37°C. Asparagine in position 18 - but not position 29 - could be substituted to glutamine without detrimental effects on Y2-receptor potency. Covalent dimers were formed via the phenol impurity benzoquinone reacting with two N-terminal residues (Isoleucine-Lysine). Both residues had to be modified to suppress dimerization, which could be done without negatively affecting Y2-receptor potency or other stability/biophysical properties. Introduction of half-life extending modifications in position 30 and 35 eliminated aggregation at 37°C without negatively affecting other stability properties. Placement of a protracting moiety (fatty acid) in the receptor-binding C-terminal region reduced Y2-receptor potency substantially, whereas only minor effects of protractor position were observed on structural, biophysical or stability properties. Lipidated PYY3-36 analogues formed oligomers of various sizes depending on primary structure and solution conditions. CONCLUSIONS: By rational design, a chemically and physically stable Y2-receptor selective, half-life extended PYY3-36 peptide has been developed.

Social media use and alcohol consumption among students in Uganda: a cross sectional study.

BACKGROUND: Globally, alcohol use significantly contributes to the disease burden. Alcohol consumption in Uganda is related to several health consequences among young people, including university students. Social media is commonly used by students to share academic information and create social networks. Among young people in high-income countries, previous studies have also shown that social media use can have negative health outcomes related to alcohol use, and associated problems. To date, similar studies conducted in low- and middle-income countries are largely missing. OBJECTIVE: To assess the prevalence of and associations between social media use and alcohol consumption among university students in Uganda. METHOD: This was a cross-sectional study among 996 undergraduate students at Makerere University. Data were collected using a questionnaire. Alcohol use in the previous 12 months was the dependent variable. The independent variable was social media use categorised as general use, alcohol-related use, and social media lurking/passive participation. Multinomial logistic regression was used to assess associations. Crude and adjusted odds ratios were reported. RESULTS: Nearly all students (97%) used social media and 39% reported alcohol use. Regular alcohol use was significantly associated with moderate (OR = 2.22, CI: 1.35-3.66) and high level general social media use (OR = 2.45, CI: 1.43-4.20). Regular alcohol use was also associated with alcohol-related social media (OR = 6.46, CI: 4.04-10.30), and alcohol-related lurking (OR = 4.59, CI: 2.84-7.39). Similar, although weaker associations were identified for occasional alcohol use. CONCLUSIONS: Approximately four in ten students reported alcohol use in the past year, and almost all students used social media. Alcohol-related social media use was associated with occasional and regular alcohol use, with stronger associations for regular use. These findings may guide further research and present an opportunity for potential alcohol control interventions to improve health among young populations in low- and middle-income countries.

Diversity, preventive work and education-matters of health and well-being in firefighter discourse.

Purpose: The aim of this study is to analyse how recurrent health hindrance themes in the firefighter discourse, identified by firefighters themselves, relate to a set of policies about diversity, preventive work and education of firefighters. The intention is further to discuss the implications of these policy initiatives and the resistance against them in terms of firefighters' health and well-being at work. Method: Firefighters from three different rescue stations in Sweden, participated in either a focus group discussion or individual interviews. Different themes in firefighter discourse that were described as hindrances to the health and well-being of firefighters were identified. A strategic sample of policy documents that relate to the very same themes was also chosen for analysis and here we combined critical discourse analysis (CDA) with critical policy analysis. Results: The health hindrance themes regarding diversity, preventive work and education that firefighters identified have in common that they relate to changes in work culture and the firefighter profession. Conclusion: In conclusion, we argue that the most important challenge for the rescue service to tackle in the future, is how to transform firefighting to be more inclusive and yet maintaining the good health and well-being that exists among the vast majority of today's firefighters.

Biosensor based on cellobiose dehydrogenase for detection of catecholamines.

A cellobiose dehydrogenase (CDH)-modified graphite electrode was designed for amperometric detection of catecholamines in the flow injection mode, by their recycling between the graphite electrode (+300 mV vs Ag|AgCl) and the reduced FAD cofactor of adsorbed CDH, resulting in an amplified response signal. The high efficiency of the enzyme-catecholamine reaction leads to a detection limit below 1 nM and a sensitivity of 15.8 A.M(-1) x cm(-2) (approximately 1150 nA/microM) for noradrenaline, with a coverage of less than 2.5 microg of CDH adsorbed on the electrode surface (0.073 cm(2)). Working parameters such as pH, cellobiose concentration, carrier buffer, and applied potential were optimized, using hydroquinone as a model analyte. The sensitivity, linear range, and amplification factor can be modulated by the steady-state concentration of cellobiose in the flow buffer. The response of the sensor decreases only 2% when run continuously for 4 h in the flow injection mode. The response peak maximum is obtained within 6 s at a flow rate of 0.5 mL/min, representing the time of the entire sample segment to pass the electrode. CDH enzymes from Phanerochaete chrysosporium and Sclerotium rolfsii were investigated, providing different characteristics of the sensor, with sensors made with CDH from P. chrysosporium being the better ones.