Modelling human pathology of traumatic brain injury in animal models

Traumatic brain injury (TBI) is caused by a head impact with a force exceeding regular exposure from normal body movement which the brain normally can accommodate. People affected include, but are not restricted to, sport athletes in American football, ice hockey, boxing as well as military personnel. Both single and repetitive exposures may affect the brain acutely and can lead to chronic neurodegenerative changes including chronic traumatic encephalopathy associated with the development of dementia. The changes in the brain following TBI include neuroinflammation, white matter lesions, and axonal damage as well as hyperphosphorylation and aggregation of tau protein. Even though the human brain gross anatomy is different from rodents implicating different energy transfer upon impact, especially rotational forces, animal models of TBI are important tools to investigate the changes that occur upon TBI at molecular and cellular levels. Importantly, such models may help to increase the knowledge of how the pathologies develop, including the spreading of tau pathologies, and how to diagnose the severity of the TBI in the clinic. In addition, animal models are helpful in the development of novel biomarkers and can also be used to test potential disease‐modifying compounds in a preclinical setting.     

The significance of early breastfeeding experiences on breastfeeding self‐efficacy one week postpartum

Many new mothers do not reach their breastfeeding goals. Breastfeeding self‐efficacy is a modifiable determinant influenced by prior and new breastfeeding experiences. More knowledge about factors associated with early breastfeeding experiences and breastfeeding self‐efficacy would allow us to qualify breastfeeding counselling and increase breastfeeding duration. This study aimed to identify prevalence and factors associated with early negative breastfeeding experience, low breastfeeding self‐efficacy in the first week postpartum, and drop in self‐efficacy from late pregnancy to early postpartum period. A prospective longitudinal study was performed in Denmark from 2013 to 2014, including 2, 804 mothers. Results showed that 1 week postpartum almost 10% of mothers had negative breastfeeding experiences, 36% had low breastfeeding self‐efficacy, and 26% drop in self‐efficacy from pregnancy. Negative breastfeeding experiences were significantly associated with epidural analgesia, interrupted skin‐to‐skin contact immediately postpartum, short previous breastfeeding duration, and lacking social support. Low breastfeeding self‐efficacy was associated with low breastfeeding intention, short previous breastfeeding duration, and negative breastfeeding experiences in the first week postpartum. Finally, significant associations of drop in breastfeeding self‐efficacy from late pregnancy were no or short education, early negative breastfeeding experiences, prior short breastfeeding duration, and low general breastfeeding self‐efficacy in pregnancy. Negative breastfeeding experiences in the first week postpartum is crucial for maternal breastfeeding self‐efficacy 1 week following birth. It is important to identify and support mothers at risk of negative breastfeeding experiences in the first week following birth and address factors that might increase the probability of early successful breastfeeding experiences.     

Motion‐compensated b‐tensor encoding for in vivo cardiac diffusion‐weighted imaging

Motion is a major confound in diffusion‐weighted imaging (DWI) in the body, and it is a common cause of image artefacts. The effects are particularly severe in cardiac applications, due to the nonrigid cyclical deformation of the myocardium. Spin echo‐based DWI commonly employs gradient moment‐nulling techniques to desensitise the acquisition to velocity and acceleration, ie, nulling gradient moments up to the 2nd order (M2‐nulled). However, current M2‐nulled DWI scans are limited to encode diffusion along a single direction at a time. We propose a method for designing b‐tensors of arbitrary shapes, including planar, spherical, prolate and oblate tensors, while nulling gradient moments up to the 2nd order and beyond. The design strategy comprises initialising the diffusion encoding gradients in two encoding blocks about the refocusing pulse, followed by appropriate scaling and rotation, which further enables nulling undesired effects of concomitant gradients. Proof‐of‐concept assessment of in vivo mean diffusivity (MD) was performed using linear and spherical tensor encoding (LTE and STE, respectively) in the hearts of five healthy volunteers. The results of the M2‐nulled STE showed that (a) the sequence was robust to cardiac motion, and (b) MD was higher than that acquired using standard M2‐nulled LTE, where diffusion‐weighting was applied in three orthogonal directions, which may be attributed to the presence of restricted diffusion and microscopic diffusion anisotropy. Provided adequate signal‐to‐noise ratio, STE could significantly shorten estimation of MD compared with the conventional LTE approach. Importantly, our theoretical analysis and the proposed gradient waveform design may be useful in microstructure imaging beyond diffusion tensor imaging where the effects of motion must be suppressed.     

IgE-mediated regulation of IL-10 and type I IFN enhances rhinovirus-induced Th2 differentiation by primary human monocytes

Rhinovirus (RV) infections are linked to the development and exacerbation of allergic diseases including allergic asthma. IgE, another contributor to atopic disease pathogenesis, has been shown to regulate DC antiviral functions and influence T cell priming by monocytes. We previously demonstrated that IgE-mediated stimulation of monocytes alters multiple cellular functions including cytokine secretion, phagocytosis, and influenza-induced Th1 development. In this study, we investigate the effects of IgE-mediated stimulation on monocyte-driven, RV-induced T cell development utilizing primary human monocyte-T cell co-cultures. We demonstrate that IgE crosslinking of RV-exposed monocytes enhances monocyte-driven Th2 differentiation. This increase in RV-induced Th2 development was regulated by IgE-mediated inhibition of virus-induced type I IFN and induction of IL-10. These findings suggest an additional mechanism by which two clinically significant risk factors for allergic disease exacerbations—IgE-mediated stimulation and rhinovirus infection—may synergistically promote Th2 differentiation and allergic inflammation.