Hyperspectral imaging and spectral unmixing for improving whole-body fluorescence cryo-imaging

Whole-animal fluorescence cryo-imaging is an established technique that enables visualization of the biodistribution of labeled drugs, contrast agents, functional reporters and cells in detail. However, many tissues produce endogenous autofluorescence, which can confound interpretation of the cryo-imaging volumes. We describe a multi-channel, hyperspectral cryo-imaging system that acquires densely-sampled spectra at each pixel in the 3-dimensional stack. This information enables the use of spectral unmixing to isolate the fluorophore-of-interest from autofluorescence and/or other fluorescent reporters. In phantoms and a glioma xenograft model, we show that the approach improves detection limits, increases tumor contrast, and can dramatically alter image interpretation.     

Sleep studies in children on long-term non-invasive respiratory support

Purpose

The aim of this study was to assess the impact of changes in respiratory support (RS) settings recommended after a titration polysomnography (PSG), in terms of daytime symptoms and quality of life.

Methods

A retrospective chart review of all RS (CPAP and bi-level ventilation) titration studies was carried out at our tertiary paediatric sleep laboratory in the past 5 years. All patients with at least two studies in the past 5 years were included in the analysis. Parents completed the obstructive sleep apnoea (OSA)-18 and Paediatric Daytime Sleepiness Scale (PDSS) questionnaires on the night of each PSG. Results are presented as means (SD).

Results

A total of 42 patients (25 on CPAP and 17 on bi-level ventilation, age 11 (6)?years) had 71 pairs of titration studies (41 CPAP and 30 bi-level). Changes in RS settings were recommended in 27 of 41 (65 %) CPAP studies and 11 of 30 (36 %) bi-level studies. Overall, changes were fully implemented by the treating physician in 55 % of cases. There was an improvement in total OSA-18 score between studies in 48 % of the paired CPAP studies and 65 % of bi-level studies. OSA-18 scores improved in 47 % of the studies where any recommended change had been implemented versus 0 % of those where none of the recommended changes had been made (p?=?0.1).

Conclusions

Titration studies frequently led to recommendations for a change in RS settings in these patients on long-term RS. Symptom scores were more likely to improve if recommendations for change were implemented by the time of the follow-up study.     

Maternal and In Utero Determinants of Type 2 Diabetes Risk in the Young

The global prevalence of diabetes mellitus has reached epidemic proportions. In 2010, it was estimated that 6.4 % of the adult population (285 million) have diabetes. In recent years, the incidence of type 2 diabetes (T2D), a condition traditionally associated with aging, has been steadily increasing among younger individuals. It is now a well-established notion that the early-life period is a critical window of development and that influences during this period can “developmentally prime” the metabolic status of the adult. This review discusses the role of maternal and in utero influences on the developmental priming of T2D risk. Both human epidemiological studies and experimental animal models are beginning to demonstrate that early dietary challenges can accelerate the onset of age-associated metabolic disturbances, including insulin resistance, T2D, obesity, hypertension, and cardiovascular disease. These findings show that poor maternal nutrition can prime a prediabetes phenotype, often manifest as insulin resistance, by very early stages of life. Thus, the maternal diet is a critical determinant of premature T2D risk. While the mechanisms that link early nutrition to age-associated metabolic decline are currently unclear, preliminary findings suggest perturbations in a number of processes involved in cellular aging, such as changes in longevity-associated Sirtuin activity, epigenetic regulation of key metabolic genes, and mitochondrial dysfunction. Preliminary studies show that pharmacological interventions in utero and dietary supplementation in early postnatal life may alleviate insulin resistance and reduce T2D risk. However, further studies are warranted to fully understand the relationship between the early environment and long-term effects on metabolism. Such mechanistic insights will facilitate strategic interventions that prevent accelerated metabolic decline and the premature onset of T2D in the current and future generations.     

Alterations in Immune Cells and Mediators in the Brain: It's Not Always Neuroinflammation!

Neuroinflammation was once a clearly defined term denoting pathological immune processes within the central nervous system (CNS). Historically, this term was used to indicate the four hallmarks of peripheral inflammaton that occur following severe CNS injuries, such as stroke, injury or infection. Recently, however, the definition of neuroinflammation has relaxed to the point that it is often now assumed to be present when even only a single classical hallmark of inflammation is measured. As a result, a wide range of disorders, from psychiatric to degenerative diseases, are now assumed to have an integral inflammatory component. Ironically, at the same time, research has revealed unexpected nonclassical immune actions of immune mediators and cells in the CNS in the absence of pathology, increasing the likelihood that homeostatic and adaptive immune processes in the CNS will be mistaken for neuroinflammation. Thus, we suggest reserving the term neuroinflammation for contexts where multiple signs of inflammation are present to avoid erroneously classifying disorders as inflammatory when they may instead be caused by nonimmune etiologies or secondary immune processes that serve adaptive roles.