Anti-Inflammatory Impact of Minocycline in a Mouse Model of Tauopathy

Alzheimer's disease (AD) is characterized by the extracellular deposition of β-amyloid in senile plaques, the intraneuronal accumulation of hyperphosphorylated tau aggregates as neurofibrillary tangles, and progressive neuronal loss leading to the onset of dementia. Increasing evidence suggests that neuroinflammatory processes contribute to the progression of AD. Minocycline is a semi-synthetic tetracycline derivative commonly used in the treatment of acne. Many studies have revealed that minocycline also has potent anti-inflammatory actions that are neuroprotective in rodent models of Huntington's disease, Parkinson's disease and motor neuron disease. Recently, we demonstrated that minocycline reduces the development of abnormal tau species in the htau mouse model of Alzheimer's disease. We have now extended these findings by examining the impact of minocycline on inflammatory processes in htau mice. Immunohistochemical analysis revealed that minocycline treatment resulted in fewer activated astrocytes in several cortical regions of htau mice, but did not affect astrocytosis in the hippocampus. We found htau mice have significantly elevated amounts of several cortical pro-inflammatory cytokines. In addition, we find that minocycline treatment significantly reduced the amounts of several inflammatory factors, including monocyte chemoattractant proteins 1 and 5, interleukins -6 and -10, eotaxin, and I-309. Furthermore, the reduced amounts of these cytokines significantly correlated with the amount of tau phosphorylated at Ser396/404 in the cortex of htau mice. These results may reveal new cytokine targets of minocycline that could be associated with its inhibition of tau pathology development in vivo. It is possible that further investigation of the role of these cytokines in neurodegenerative processes may identify novel therapeutic targets for Alzheimer's disease and related disorders

A simplified model for minor and major loop magnetic hysteresis and its application for inference of temperature in induction heated particle beds

In this work, a LangArc model is presented that successfully fits both major and minor hysteresis loops of a bed of magnetic particles in real time using instruments that detect changes in the magnetic field strength, such as in-situ pick-up coils. A novel temperature measurement application is demonstrated based on a real-time characterisation of a magnetic material, in this case magnetite, as a function of temperature. Magnetic hysteresis can be used to provide useful induction heating in a packed bed of magnetic materials. This can be used for general heating and to provide energy to chemical reactions in chemical processes. Accurate temperature measurement of magnetic particles under induction heating is a well-known challenge: conventional techniques give a single-point measurement, and are subject to inaccuracy due to self-heating of the instrument tip. Thermal lag can be problematic given the rapid heating rates that are characteristic of induction heating. The LangArc inferred temperature measurement technique is shown to detect heating rates in excess of 30 °C·s−1, under which circumstances an in-bed thermocouple was shown to lag by as much as 180 °C. This new method has significant importance for temperature measurement in applications involving the induction heating of magnetic materials as it avoids the location of an instrument inside the magnetic particle bed and is highly responsive under rapid heating where other techniques can give misleading results.</p

Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients

Peer reviewedPublisher PD

Intramuscular fat in ambulant young adults with bilateral spastic cerebral palsy

BACKGROUND: It is known that individuals with bilateral spastic cerebral palsy (BSCP) have small and weak muscles. However, no studies to date have investigated intramuscular fat infiltration in this group. The objective of this study is to determine whether adults with BSCP have greater adiposity in and around their skeletal muscles than their typically developing (TD) peers as this may have significant functional and cardio-metabolic implications for this patient group. METHODS: 10 young adults with BSCP (7 male, mean age 22.5 years, Gross Motor Function Classification System (GMFCS) levels I-III), and 10 TD young adults (6 male, mean age 22.8 years) took part in this study. 11 cm sections of the left leg of all subjects were imaged using multi-echo gradient echo chemical shift imaging (mDixon). Percentage intermuscular fat (IMAT), intramuscular fat (IntraMF) and a subcutaneous fat to muscle volume ratio (SF/M) were calculated. RESULTS: IntraMF was higher with BSCP for all muscles (p = 0.001-0.013) and was significantly different between GMFCS levels (p < 0.001), with GMFCS level III having the highest IntraMF content. IMAT was also higher with BSCP p < 0.001). No significant difference was observed in SF/M between groups. CONCLUSION: Young adults with BSCP have increased intermuscular and intramuscular fat compared to their TD peers. The relationship between these findings and potential cardio-metabolic and functional sequelae are yet to be investigated

The influence of cognitive-perceptual variables on patterns of change over time in rural midlife and older women\u27s healthy eating.

Although studies demonstrate that dietary interventions for healthy adults can result in beneficial dietary changes, few studies examine when and how people change in response to these interventions, particularly in rural populations. The purpose of this study was to examine patterns of change over time in healthy eating behaviors in midlife and older women in response to a one-year health-promoting intervention, and to examine what predictors (perceived benefits, barriers, self-efficacy, and family support for healthy eating) influence the changes during the intervention and follow-up. Data for this secondary analysis were from the Wellness for Women community-based trial. Women (N = 225) between the ages of 50-69 in rural Nebraska, U.S.A., were recruited. A repeated-measures experimental design was used with randomization of two rural counties to intervention (tailored newsletter) or comparison (standard newsletter) groups. Eating behavior was measured by the Healthy Eating Index. The predictor variables were assessed using standard measures. Data analysis was done using latent growth curve modeling. The tailored newsletter group was successful in improving their healthy eating behavior compared to the standard newsletter group during the one-year intervention, at the end of the intervention, and during the follow-up phase. Family support at the end of the intervention was positively associated with healthy eating at the end of the intervention. Perceived barriers had the strongest impact on healthy eating behavior at all time points. Compared to participants in the standard newsletter group, those in the tailored newsletter group perceived more family support and fewer barriers for healthy eating at the end of the intervention (mediation effects). Based on these findings, both family support and perceived barriers should be central components of interventions focused on healthy eating behavior in rural midlife and older women

The influence of cognitive-perceptual variables on patterns of change over time in rural midlife and older women\u27s healthy eating

Although studies demonstrate that dietary interventions for healthy adults can result in beneficial dietary changes, few studies examine when and how people change in response to these interventions, particularly in rural populations. The purpose of this study was to examine patterns of change over time in healthy eating behaviors in midlife and older women in response to a one-year health-promoting intervention, and to examine what predictors (perceived benefits, barriers, self-efficacy, and family support for healthy eating) influence the changes during the intervention and follow-up. Data for this secondary analysis were from the Wellness for Women community-based trial. Women (N ¼ 225) between the ages of 50e69 in rural Nebraska, U.S.A., were recruited. A repeated-measures experimental design was used with randomization of two rural counties to intervention (tailored newsletter) or comparison (standard newsletter) groups. Eating behavior was measured by the Healthy Eating Index. The predictor variables were assessed using standard measures. Data analysis was done using latent growth curve modeling. The tailored newsletter group was successful in improving their healthy eating behavior compared to the standard newsletter group during the one-year intervention, at the end of the intervention, and during the follow-up phase. Family support at the end of the intervention was positively associated with healthy eating at the end of the intervention. Perceived barriers had the strongest impact on healthy eating behavior at all time points. Compared to participants in the standard newsletter group, those in the tailored newsletter group perceived more family support and fewer barriers for healthy eating at the end of the intervention (mediation effects). Based on these findings, both family support and perceived barriers should be central components of interventions focused on healthy eating behavior in rural midlife and older women

Catchment-wide interactive effects of anthropogenic structures and river levels on fish spawning migrations

Worldwide, rivers are extensively fragmented by anthropogenic structures, reducing longitudinal connectivity, inhibiting migration and leading to severe declines in many fish populations, especially for diadromous species. However, few studies have determined the effects of annual differences in hydrology on catchment penetration past barriers to spawning habitats. We investigated the upstream spawning migration of 120 (n = 61 & 59) acoustic tagged river lamprey (Lampetra fluviatilis) across two contrasting (dry and wet) years in the River Yorkshire Ouse, England. Overall, significantly more lamprey reached spawning habitat (76% vs 39%) and penetrated significantly further upstream (median [km] from release, 53.9 vs 16.8) in the wet year than the dry year. Passage at weirs was almost exclusively during elevated river levels, which directly and collectively influenced catchment-wide distribution, especially in the dry year. Indeed, higher proportions entered two upper tributaries in the wet year (9.8% vs 27.1% and 9.8% vs 30.5%), due to increased passage efficiencies at the two main river weirs (60.5–87.5% and 54.5–83.8%), and reached assumed spawning locations 66.5% and 10.9% quicker. By contrast, there was no difference in numbers of lamprey entering, or time taken to arrive at assumed spawning location, in the two lower river tributaries between years. Our study supports the landscape-scale paradigm for ecosystem restoration because of the observed catchment-level effects of hydrology and barrier distribution on fish migration. Connectivity restoration for migratory fish should be implemented at a catchment scale, with planning incorporating spatial information regarding accessibility to key habitats to reap the largest gains

Diurnal and stress-induced intra-hippocampal corticosterone rise attenuated in 11β-HSD1-deficient mice:a microdialysis study in young and aged mice

11β‐Hydroxysteroid dehydrogenase type 1 (11β‐HSD1) locally regenerates active glucocorticoids from their inert forms thereby amplifying intracellular levels within target tissues including the brain. We previously showed greater increases in intra‐hippocampal corticosterone (CORT) levels upon Y‐maze testing in aged wild‐type than in 11β‐HSD1(−/−) mice coinciding with impaired and intact spatial memory, respectively. Here we examined whether ageing influences 11β‐HSD1 regulation of CORT in the dorsal hippocampus under basal conditions during the diurnal cycle and following stress. Intra‐hippocampal CORT levels measured by in vivo microdialysis in freely behaving wild‐type mice displayed a diurnal variation with peak levels in the evening that were significantly elevated with ageing. In contrast, the diurnal rise in intra‐hippocampal CORT levels was greatly diminished in 11β‐HSD1(−/−) mice and there was no rise with ageing; basal intra‐hippocampal CORT levels were similar to wild‐type controls. Furthermore, a short (3 min) swim stress induced a longer lasting increase in intra‐hippocampal CORT levels in wild‐type mice than in 11β‐HSD1(−/−) mice despite no genotypic differences in elevation of plasma CORT. These data indicate that 11β‐HSD1 activity contributes substantially to diurnal and stress‐induced increases in hippocampal CORT levels. This contribution is even greater with ageing. Thus, 11β‐HSD1 inhibition may be an attractive target for treating cognitive impairments associated with stress or ageing