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In Krabbe’s Disease (KD), a leukodystrophy caused by β-galactosylceramidase deficiency, demyelination and a myelin-independent axonopathy contribute to the severe neuropathology. Beyond axonopathy, we show that in Twitcher mice, a model of KD, a decreased number of axons both in the PNS and CNS, and of neurons in dorsal root ganglia (DRG), occurred before the onset of demyelination. Despite the early axonal loss, and although in vitro Twitcher neurites degenerated over time, Twitcher DRG neurons displayed an initial neurite overgrowth and, following sciatic nerve injury, Twitcher axons were regeneration-competent, at a timepoint where axonopathy was already ongoing. Psychosine, the toxic substrate that accumulates in KD, induced lipid raft clustering. At the mechanistic level, TrkA recruitment to lipid rafts was dysregulated in Twitcher neurons, and defective activation of the ERK1/2 and AKT pathways was identified. Besides defective recruitment of signaling molecules to lipid rafts, the early steps of endocytosis and the transport of endocytic and synaptic vesicles were impaired in Twitcher DRG neurons. Defects in axonal transport, specifically in the retrograde component, correlated with decreased levels of dynein, abnormal levels of post-translational tubulin modifications and decreased microtubule stability. The identification of the axonal defects that precede demyelination in KD, together with the finding that Twitcher axons are regeneration-competent when axonopathy is already installed, open new windows of action to effectively correct the neuropathology that characterizes this disorder.

BackgroundThe provision of Intensive Care (IC) can lead to a health care provider’s physical, psychological and emotional exhaustion, which may develop into burnout. We notice the absence of specific studies regarding this syndrome in Portuguese Intensive Care Units (ICUs). Our main objective is to study the incidence and risk factors of burnout in Portuguese ICUs.MethodsA self-fulfilment questionnaire containing 3 items: (i) socio-demographic data of the study population; (ii) experiences in the workplace; (iii) Maslach Burnout Inventory (MBI) - was applied to evaluate the influence of distinct factors on the prevalence of burnout among physicians and nurses working in ICUs.ResultsThree hundred professionals (82 physicians and 218 nurses) from ten ICUs were included in the study, out of a total of 445 who were eligible. There was a high rate of burnout among professionals working in Portuguese ICUs, with 31% having a high level of burnout. However, when burnout levels among nurses and physicians were compared, no significant difference was found. Using multivariate analysis, we identified gender as being a risk factor, where female status increases the risk of burnout. In addition, higher levels of burnout were associated with conflicts and ethical decision making regarding withdrawing treatments. Having a temporary work contract was also identified as a risk factor. Conversely, working for another service of the same health care institution acts as a protective factor.ConclusionsA high rate of burnout was identified among professionals working in Portuguese ICUs. This study highlights some new risk factors for burnout (ethical decision making, temporary work contracts), and also protective ones (maintaining activity in other settings outside the ICU) that were not previously reported. Preventive and interventive programmes to avoid and reduce burnout syndrome are of paramount importance in the future organization of ICUs and should take the above results into account.

Introduction: Age-related changes in muscle mass and muscle tissue composition contribute to diminished strength in older adults. The objectives of this study are to examine if an assessment method using mobile diagnostic ultrasound augments well-known determinants of lean body mass (LBM) to aid sarcopenia staging, and if a sonographic measure of muscle quality is associated with muscle performance.Methods: Twenty community-dwelling female subjects participated in the study (age = 43.4 ± 20.9 years; BMI: 23.8, interquartile range: 8.5). Dual energy X-ray absorptiometry (DXA) and diagnostic ultrasound morphometry were used to estimate LBM. Muscle tissue quality was estimated via the echogenicity using grayscale histogram analysis. Peak force was measured with grip dynamometry and scaled for body size. Bivariate and multiple regression analyses were used to determine the association of the predictor variables with appendicular lean mass (aLM/ht2), and examine the relationship between scaled peak force values and muscle echogenicity. The sarcopenia LBM cut point value of 6.75 kg/m2 determined participant assignment into the Normal LBM and Low LBM subgroups.Results: The selected LBM predictor variables were body mass index (BMI), ultrasound morphometry, and age. Although BMI exhibited a significant positive relationship with aLM/ht2 (adj. R2 = 0.61, p < 0.001), the strength of association improved with the addition of ultrasound morphometry and age as predictor variables (adj. R2 = 0.85, p < 0.001). Scaled peak force was associated with age and echogenicity (adj. R2 = 0.53, p < 0.001), but not LBM. The Low LBM subgroup of women (n = 10) had higher scaled peak force, lower BMI, and lower echogenicity values in comparison to the Normal LBM subgroup (n = 10; p < 0.05).Conclusions: Diagnostic ultrasound morphometry values are associated with LBM, and improve the BMI predictive model for aLM/ht2 in women. In addition, ultrasound proxy measures of muscle quality are more strongly associated with strength than muscle mass within the study sample.

Os achados reforçam a necessidade da avaliação do medo de cair entre os idosos que residem no próprio domicílio, assim como o desenvolvimento e a utilização de estratégias pelos profissionais voltadas para os fatores modificáveis,de modo a reduzir as quedas e melhorar o estado de saúde, o que pode contribuir para a diminuição do medo de cair entre os idosos.

Ethical problems were reported at different levels by physicians and nurses. The type of ethical decisions made by nurses working in Portuguese ICUs had an impact on burnout levels. This did not apply to physicians. This study highlights the need for education in the field of ethics in ICUs and the need to foster inter-disciplinary discussion so as to encourage ethical team deliberation in order to prevent burnout.

Although neglected by science for a long time, the olfactory sense is now the focus of a panoply of studies that bring new insights and raises interesting questions regarding its functioning. The importance in the clarification of this process is of interest for science, but also motivated by the food and perfume industries boosted by a consumer society with increasingly demands for higher quality standards. In this review, a general overview of the state of art of science regarding the olfactory sense is presented with the main focus on the peripheral olfactory system. Special emphasis will be given to the deorphanization of the olfactory receptors (ORs), a critical issue because the specificity and functional properties of about 90% of human ORs remain unknown mainly due to the difficulties associated with the functional expression of ORs in high yields.

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