Mixing induces long-term hyperthermia in growing pigs

The purpose of this experiment was to determine whether body temperature is a sensitive parameter to measure long-term effects of stress in pigs. Mixing of unacquainted pigs is a severe stressor that has detrimental effects on health, production and welfare. We measured deep body temperature after mixing growing pigs. Five pigs of 15 weeks of age, each individually housed with a companion pig, were mixed with two unacquainted congeners. Deep body temperature, heart rate and activity were recorded by radiotelemetry 9 days prior to until 8 days after mixing. These parameters were also recorded in dive control pigs (individually housed with a companion pig) during the same time span. Behaviour during the light period was recorded on videotape on the day of mixing and on three subsequent days. Mixing induced a significant rise ill body temperature that lasted for 8 h after mixing. Although heart rate and general activity level did not significantly differ between mixed and control pigs, mixing significantly increased the frequency of fighting and reduced the frequency of earing. In conclusion, the present experiment shows that mixing induces a long-lasting hyperthermia in pigs. Thus, deep body temperature may be used as a sensitive parameter to measure long-term effects of stress in pigs

Mobile vaccination units to increase COVID-19 vaccination uptake in areas with lower coverage:a within-neighbourhood analysis using national registration data, the Netherlands, September-December 2021

BackgroundVaccine uptake differs between social groups. Mobile vaccination units (MV-units) were deployed in the Netherlands by municipal health services in neighbourhoods with low uptake of COVID-19 vaccines.AimWe aimed to evaluate the impact of MV-units on vaccine uptake in neighbourhoods with low vaccine uptake.MethodsWe used the Dutch national-level registry of COVID-19 vaccinations (CIMS) and MV-unit deployment registrations containing observations in 253 neighbourhoods where MV-units were deployed and 890 contiguous neighbourhoods (total observations: 88,543 neighbourhood-days). A negative binomial regression with neighbourhood-specific temporal effects using splines was used to study the effect.ResultsDuring deployment, the increase in daily vaccination rate in targeted neighbourhoods ranged from a factor 2.0 (95% confidence interval (CI): 1.8-2.2) in urbanised neighbourhoods to 14.5 (95% CI: 11.6-18.0) in rural neighbourhoods. The effects were larger in neighbourhoods with more voters for the Dutch conservative Reformed Christian party but smaller in neighbourhoods with a higher proportion of people with non-western migration backgrounds. The absolute increase in uptake over the complete intervention period ranged from 0.22 percentage points (95% CI: 0.18-0.26) in the most urbanised neighbourhoods to 0.33 percentage point (95% CI: 0.28-0.37) in rural neighbourhoods.ConclusionDeployment of MV-units increased daily vaccination rate, particularly in rural neighbourhoods, with longer travel distance to permanent vaccination locations. This public health intervention shows promise to reduce geographic and social health inequalities, but more proactive and long-term deployment is required to identify its potential to substantially contribute to overall vaccination rates at country level.</p

Direct AMPK activation corrects NASH in rodents through metabolic effects and direct action on inflammation and fibrogenesis

No approved therapies are available for nonalcoholic steatohepatitis (NASH). Adenosine monophosphate–activated protein kinase (AMPK) is a central regulator of cell metabolism; its activation has been suggested as a therapeutic approach to NASH. Here we aimed to fully characterize the potential for direct AMPK activation in preclinical models and to determine mechanisms that could contribute to efficacy for this disease. A novel small-molecule direct AMPK activator, PXL770, was used. Enzyme activity was measured with recombinant complexes. De novo lipogenesis (DNL) was quantitated in vivo and in mouse and human primary hepatocytes. Metabolic efficacy was assessed in ob/ob and high-fat diet–fed mice. Liver histology, biochemical measures, and immune cell profiling were assessed in diet-induced NASH mice. Direct effects on inflammation and fibrogenesis were assessed using primary mouse and human hepatic stellate cells, mouse adipose tissue explants, and human immune cells. PXL770 directly activated AMPK in vitro and reduced DNL in primary hepatocytes. In rodent models with metabolic syndrome, PXL770 improved glycemia, dyslipidemia, and insulin resistance. In mice with NASH, PXL770 reduced hepatic steatosis, ballooning, inflammation, and fibrogenesis. PXL770 exhibited direct inhibitory effects on pro-inflammatory cytokine production and activation of primary hepatic stellate cells. Conclusion: In rodent models, direct activation of AMPK is sufficient to produce improvements in all core components of NASH and to ameliorate related hyperglycemia, dyslipidemia, and systemic inflammation. Novel properties of direct AMPK activation were also unveiled: improved insulin resistance and direct suppression of inflammation and fibrogenesis. Given effects also documented in human cells (reduced DNL, suppression of inflammation and stellate cell activation), these studies support the potential for direct AMPK activation to effectively treat patients with NASH

Magnitude, precision, and realism of depth perception in stereoscopic vision

Our perception of depth is substantially enhanced by the fact that we have binocular vision. This provides us with more precise and accurate estimates of depth and an improved qualitative appreciation of the three-dimensional (3D) shapes and positions of objects. We assessed the link between these quantitative and qualitative aspects of 3D vision. Specifically, we wished to determine whether the realism of apparent depth from binocular cues is associated with the magnitude or precision of perceived depth and the degree of binocular fusion. We presented participants with stereograms containing randomly positioned circles and measured how the magnitude, realism, and precision of depth perception varied with the size of the disparities presented. We found that as the size of the disparity increased, the magnitude of perceived depth increased, while the precision with which observers could make depth discrimination judgments decreased. Beyond an initial increase, depth realism decreased with increasing disparity magnitude. This decrease occurred well below the disparity limit required to ensure comfortable viewing

Asymmetric Synthesis of the Epimeric (3S)-3-((E)-Hex-1-enyl)-2-methylcyclohexanones

The asymmetric rhodium-catalysed 1,4-addition of alkenylzirconium reagents to 2-cyclohexenone can be useful in the synthesis of 3-alkenyl-2-methylcyclohexanones, provided that formaldehyde is used in trapping the intermediate zirconium enolates. In this manner a four-step sequence leading to the two epimeric 3-hexenyl-2-methylcyclohexanones in enantiomeric form was developed