Workplace building design and office‐based workers' activity: a study of a natural experiment

Objective : This opportunistic natural study investigated the effects of relocation of office workers from a 30‐year‐old building to a new purpose‐built building. The new building included an attractive central staircase that was easily accessed and negotiated, as well as breakout spaces and a centralised facilities area. The researchers aimed to determine the impact of the purpose‐built office building on the office workers' sedentariness and level of physical activity. Method : In 2013, a natural pre‐post study was undertaken with office‐based workers in their old conventional 1970s building and on relocating to a new purpose‐built ‘activity permissive’ building. Objective movement data was measured using accelerometers. Anthropometric and demographic data was also collected. Results : Forty‐two office‐based workers significantly decreased their percentage of daily sitting time (T1 = 84.9% to T2=79.7%; p<0.001) and increased their percentage of daily standing time (T1=11.2% to T2 17.0%; p<0.001) in the new building. Moderate activity significantly declined (T1=3.9% to 3.2%=T2; p=0.038). There was a significant decrease in mean minutes of sitting time (19.62 minutes; p<0.001) and increase in standing time (22.03 minutes; p<0.001). Conclusions : The design of a building can influence activity. This opportunistic study on the impact of workplace relocation on office‐based workers' activity showed modest positive outcomes in sitting and standing. Evidence is required to inform building design policy and practice that supports physical activity and reduces levels of sedentariness in the workplace.     

Plasma 1,5-anhydroglucitol concentrations are influenced by variations in the renal threshold for glucose.

AIMS: Measurement of serum 1,5-anhydroglucitol (1,5AG) concentrations has been proposed as an alternative to HbA1c as both a marker of diabetic glycaemic control and as a screening test for diabetes. The sugar competes with glucose for renal tubular reabsorption, so hyperglycaemia leads to reduced serum 1,5AG concentrations through increased urinary loss. This study has sought to establish whether plasma 1,5AG can be influenced by not only hyperglycaemia, but by variations in renal threshold for glucose. METHODS: Thirty-eight pregnant women (median age 30 years, range 20-43) found to be normoglycaemic after a 75-g carbohydrate load had plasma 1,5AG and urine glucose measured. RESULTS: Using multivariate analysis, the presence and degree of detectable glycosuria at 2 h post glucose load was strongly predictive of a low plasma 1,5AG concentration (P=0.0012) independently of fasting plasma glucose (P=0.96), 2 h glucose (P=0.029), subject age (P=0.97) and gestation (P=0.36). Thus, when matched for plasma glucose areas under the glucose load curve, 16 glycosuric subjects had significantly lower 1,5AG concentrations compared to 16 nonglycosuric ones (median 1,5AG 46 micromol/l (IQR 30-56) vs. 72 micromol/l (IQR 55-79, P=0.017). CONCLUSIONS: People with the same glucose tolerance may demonstrate variable plasma 1,5AG concentrations depending on their renal threshold for glucose. This inherent characteristic is likely to limit the usefulness of the test when monitoring or screening for diabetes.     

Intravitreal HDAC Inhibitor Belinostat Effectively Eradicates Vitreous Seeds Without Retinal Toxicity In Vivo in a Rabbit Retinoblastoma Model

PurposeCurrent melphalan-based regimens for intravitreal chemotherapy for retinoblastoma vitreous seeds are effective but toxic to the retina. Thus, alternative agents are needed. Based on the known biology of histone deacetylases (HDACs) in the retinoblastoma pathway, we systematically studied whether the HDAC inhibitor belinostat is a viable, molecularly targeted alternative agent for intravitreal delivery that might provide comparable efficacy, without toxicity.MethodsIn vivo pharmacokinetic experiments in rabbits and in vitro cytotoxicity experiments were performed to determine the 90% inhibitory concentration (IC₉₀). Functional toxicity by electroretinography and structural toxicity by optical coherence tomography (OCT), OCT angiography, and histopathology were evaluated in rabbits following three injections of belinostat 350 µg (2× IC₉₀) or 700 µg (4× IC₉₀), compared with melphalan 12.5 µg (rabbit equivalent of the human dose). The relative efficacy of intravitreal belinostat versus melphalan to treat WERI-Rb1 human cell xenografts in rabbit eyes was directly quantified. RNA sequencing was used to assess belinostat-induced changes in RB cell gene expression.ResultsThe maximum nontoxic dose of belinostat was 350 µg, which caused no reductions in electroretinography parameters, retinal microvascular loss on OCT angiography, or retinal degeneration. Melphalan caused severe retinal structural and functional toxicity. Belinostat 350 µg (equivalent to 700 µg in the larger human eye) was equally effective at eradicating vitreous seeds in the rabbit xenograft model compared with melphalan (95.5% reduction for belinostat, P < 0.001; 89.4% reduction for melphalan, P < 0.001; belinostat vs. melphalan, P = 0.10). Even 700 µg belinostat (equivalent to 1400 µg in humans) caused only minimal toxicity. Widespread changes in gene expression resulted.ConclusionsMolecularly targeted inhibition of HDACs with intravitreal belinostat was equally effective as standard-of-care melphalan but without retinal toxicity. Belinostat may therefore be an attractive agent to pursue clinically for intravitreal treatment of retinoblastoma.     

Fevers and the social costs of acute infection in wild vervet monkeys

Fevers are considered an adaptive response by the host to infection. For gregarious animals, however, fever and the associated sickness behaviors may signal a temporary loss of capacity, offering other group members competitive opportunities. We implanted wild vervet monkeys (Chlorocebus pygerythrus) with miniature data loggers to obtain continuous measurements of core body temperature. We detected 128 fevers in 43 monkeys, totaling 776 fever-days over a 6-year period. Fevers were characterized by a persistent elevation in mean and minimum 24-h body temperature of at least 0.5 °C. Corresponding behavioral data indicated that febrile monkeys spent more time resting and less time feeding, consistent with the known sickness behaviors of lethargy and anorexia, respectively. We found no evidence that fevers influenced the time individuals spent socializing with conspecifics, suggesting social transmission of infection within a group is likely. Notably, febrile monkeys were targeted with twice as much aggression from their conspecifics and were six times more likely to become injured compared to afebrile monkeys. Our results suggest that sickness behavior, together with its agonistic consequences, can carry meaningful costs for highly gregarious mammals. The degree to which social factors modulate the welfare of infected animals is an important aspect to consider when attempting to understand the ecological implications of disease.

Evolutionary studies of animal behavior generally focus on the adaptive value of typical behavior in healthy animals. It has long been recognized, however, that sick animals can also provide insights into the behavioral determinants of survival and adaptation, particularly in the face of environmental challenges (1). The occurrence of fevers in a diverse range of animals (1) suggests that, despite the significant metabolic costs associated with the maintenance of elevated body temperatures (2), the fever response is an evolutionarily conserved strategy, acting principally to fight off infectious pathogens or other noninfectious irritants (3).The behavioral responses that accompany fevers are similarly considered to be complementary and beneficial (1, 4, 5) rather than maladaptive byproducts of an inability to cope with infection (6). Collectively referred to as “sickness behavior,” responses such as lethargy, anorexia, loss of body weight, sleepiness, and the cessation of grooming can all help alleviate the body’s increased metabolic demand when fighting infection (1, 7). Importantly, however, the survival benefits of sickness behavior must be traded against costs incurred such as increased risk of predation, a reduction in social engagement and reproductive opportunities, or reduced territorial defense (8). For gregarious species experiencing local competition for resources (9), detectable evidence of sickness behavior may offer group members the opportunity to gain competitive advantage through the targeted aggression of debilitated rivals. Yet, to date there is no record of increased aggression toward infected conspecifics. Birds (10) and rats (11) reduced aggressive behavior when sickness behaviors were artificially induced, and wild mongoose showed no change in agonistic behavior when sick (12). Cues of sickness, however, may allow conspecifics to identify individuals less likely to engage in aggressive encounters. Such detection, coupled with reduced rates of aggression, could explain why male house finches preferentially feed near infected conspecifics (13). Humans detect sick individuals using both visual and olfactory cues (14), and there is evidence to suggest that some nonhuman primates use olfactory cues to detect conspecifics infected with parasites (15). However, it remains unclear to what extent nonhuman primates can detect sickness itself and whether this affects the behavior of conspecifics toward sick individuals (7, 16, 17).Here, we use continuous measurements of core body temperature and corresponding behavioral data to identify naturally occurring fevers in wild vervet monkeys (Chlorocebus pygerythrus) and to test the prediction that monkeys would spend more time resting (lethargy) and less time foraging (anorexia) when febrile. On the assumption that sickness behavior can be detected, if it occurs, by conspecifics, we then assessed the possibility that conspecifics reduced their social engagement with febrile individuals and vice versa. Finally, we tested the prediction that, if the weakened status of a febrile monkey can be detected, then they would receive more conspecific aggression and that a reduced capacity to mount a viable behavioral defense would lead to an increased likelihood of injury.