Obesity, diet quality and absenteeism in a working population

The relationship between workplace absenteeism and adverse lifestyle factors (smoking, physical inactivity and poor dietary patterns) remains ambiguous. Reliance on self-reported absenteeism and obesity measures may contribute to this uncertainty. Using objective absenteeism and health status measures, the present study aimed to investigate what health status outcomes and lifestyle factors influence workplace absenteeism. Cross-sectional data were obtained from a complex workplace dietary intervention trial, the Food Choice at Work Study. Four multinational manufacturing workplaces in Cork, Republic of Ireland. Participants included 540 randomly selected employees from the four workplaces. Annual count absenteeism data were collected. Physical assessments included objective health status measures (BMI, midway waist circumference and blood pressure). FFQ measured diet quality from which DASH (Dietary Approaches to Stop Hypertension) scores were constructed. A zero-inflated negative binomial (zinb) regression model examined associations between health status outcomes, lifestyle characteristics and absenteeism. The mean number of absences was 2·5 (sd 4·5) d. After controlling for sociodemographic and lifestyle characteristics, the zinb model indicated that absenteeism was positively associated with central obesity, increasing expected absence rate by 72 %. Consuming a high-quality diet and engaging in moderate levels of physical activity were negatively associated with absenteeism and reduced expected frequency by 50 % and 36 %, respectively. Being in a managerial/supervisory position also reduced expected frequency by 50 %. To reduce absenteeism, workplace health promotion policies should incorporate recommendations designed to prevent and manage excess weight, improve diet quality and increase physical activity levels of employees.

Steroid induced neuroprotection of damaged photoreceptor cells

Retinitis Pigmentosa (RP) is the name given to a group of hereditary diseases causing progressive and degenerative blindness. RP affects over 1 in 4000 individuals, making it the most prevalent inherited retinal disease worldwide, yet currently there is no cure. In 2011, our group released a paper detailing the protective effects of the synthetic progestin ‘Norgestrel’. A common component of the female oral contraceptive pill, Norgestrel was shown to protect against retinal cell death in two distinct mouse models of retinal degeneration: in the Balb/c light damage model and the Pde6brd10 (rd10) model. Little was known of the molecular workings of this compound however and thus this study aimed to elucidate the protective manner in which Norgestrel worked. To this aim, the 661W cone photoreceptor-like cell line and ex vivo retinal explanting was utilised. We found that Norgestrel induces a increase in neuroprotective basic fibroblast growth factor (bFGF) with subsequent downstream actions on the inhibition of glycogen synthase kinase 3β. Progesterone receptor expression was subsequently characterised in the C57 and rd10 retinas and in the 661W cell line. Norgestrel caused nuclear trafficking of progesterone receptor membrane complex one (PGRMC1) in 661W cells and thus Norgestrel was hypothesised to work primarily through the actions of PGRMC1. This trafficking was shown to be responsible for the critical upregulation of bFGF and PGRMC1- Norgestrel binding was proven to cause a neuroprotective bFGF-mediated increase in intracellular calcium. The protective properties of Norgestrel were further studied in the rd10 mouse model of retinitis pigmentosa. Using non-invasive diet supplementation (80mg/kg), we showed that Norgestrel gave significant retinal protection out to postnatal day 40 (P40). Overactive microglia have previously been shown to potentiate photoreceptor cell loss in the degenerating rd10 retina and thus we focussed on Norgestrel-mediated changes in photoreceptor-microglial crosstalk. Norgestrel acted to dampen pro-inflammatory microglial cell reactivity, decreasing chemokine (MCP1, MCP3, MIP-1α, MIP-1β) and subsequent damaging cytokine (TNFα, Il-1β) production. Critically, Norgestrel up-regulated photoreceptor-microglial, fractalkine-CX3CR1 signalling 1000-fold in the P20 rd10 mouse. Known to prevent microglial activation, we hypothesise that Norgestrel acts as a vital anti-inflammatory in the diseased retina, driving fractalkine-CX3CR1 signalling to delay retinal degeneration. This study stands to highlight some of the neuroprotective mechanisms utilised by Norgestrel in the prevention of photoreceptor cell death. We identify for the first time, not only a pro-survival pathway activated directly in photoreceptor cells, but also a Norgestreldriven mediation of an otherwise damaging microglial cell response. All taken, these results form the beginning of a case to bring Norgestrel to clinical trials, as a potential therapeutic for the treatment of RP.