“Perimortem” total body CT-scan examination in severely injured children: an informative insight into the causes of death

International Journal of Legal Medicine - To report routine practice of “perimortem” CT-scan imaging to determine the causes of death in children dying from severe accidental injuries...     

Zur Aetiologie der „zapfenförmigen Fortsätze” am Kleinhirn

Ohne ZusammenfassungHierzu Taf. XI und XII.     

Quantification of Demodex folliculorum by PCR in rosacea and its relationship to skin innate immune activation

The aim of this study is to quantify D. folliculorum colonisation in rosacea subtypes and age‐matched controls and to determine the relationship between D. folliculorum load, rosacea subtype and skin innate immune system activation markers. We set up a multicentre, cross‐sectional, prospective study in which 98 adults were included: 50 with facial rosacea, including 18 with erythematotelangiectatic rosacea (ETR), and 32 with papulopustular rosacea (PPR) and 48 age‐ and sex‐matched healthy volunteers. Non‐invasive facial samples were taken to quantify D. folliculorum infestation by quantitative PCR and evaluate inflammatory and immune markers. Analysis of the skin samples show that D. folliculorum was detected more frequently in rosacea patients than age‐matched controls (96% vs 74%, P < 0.01). D. folliculorum density was 5.7 times higher in rosacea patients than in healthy volunteers. Skin sample analysis showed a higher expression of genes encoding pro‐inflammatory cytokines (Il‐8, Il‐1b, TNF‐a) and inflammasome‐related genes (NALP‐3 and CASP‐1) in rosacea, especially PPR. Overexpression of LL‐37 and VEGF, as well as CD45RO, MPO and CD163, was observed, indicating broad immune system activation in patients with rosacea. In conclusion, D. folliculorum density is highly increased in patients with rosacea, irrespective of rosacea subtype. There appears to be an inverse relationship between D. folliculorum density and inflammation markers in the skin of rosacea patients, with clear differences between rosacea subtypes.     

Cellular localization and activity of Ad-delivered GFP-CFTR in airway epithelial and tracheal cells

Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and the cellular trafficking of the CFTR protein is an essential factor that determines its function in cells. The aim of our study was to develop an Ad vector expressing a biologically active green fluorescent protein (GFP)-CFTR chimera that can be tracked by both its localization and chloride channel function. No study thus far has demonstrated a GFP-CFTR construct that displayed both of these functions in the airway epithelia. Tracheal glandular cells, MM39 (CFTRwt) and CF-KM4 (CFTRDeltaF508), as well as human airway epithelial cells from a patient with cystic fibrosis (CF-HAE) and from a healthy donor (HAE) were used for the functional analysis of our Ad vectors, Ad5/GFP-CFTRwt and Ad5/GFP-CFTRDeltaF508. The GFP-CFTRwt protein expressed was efficiently addressed to the plasma membrane of tracheal cells and to the apical surface of polarized CF-HAE cells, while GFP-CFTRDeltaF508 mutant was sequestered intracellularly. The functionality of the GFP-CFTRwt protein was demonstrated by its capacity to correct the chloride channel activity both in CF-KM4 and CF-HAE cells after Ad transduction. A correlation between the proportion of Ad5-transduced CF-KM4 cells and correction of CFTR function showed that 55 to 70% transduction resulted in 70% correction of the Cl- channel function. In reconstituted CF-HAE, GFP-CFTRwt appeared as active as the nontagged CFTRwt protein in correcting the transepithelial Cl- transport. We show for the first time a GFP-CFTR chimera that localized to the apical surface of human airway epithelia and restored epithelial chloride transport to similar levels as nontagged CFTR.     

The phosphoinositide-phospholipase C (PI-PLC) pathway in the mouse oocyte

As highlighted in this review, the phosphoinositide-phospholipase C pathway is strongly implicated in the control of mouse oocyte meiosis. The pathway becomes progressively functional as oocyte growth advances, and it appears to play a role in the G2/M transition when meiosis resumes, at least in the in vitro spontaneous model. Even if the inositol 1,4,5-trisphosphate receptors are present from the beginning, they function and release Ca2+ when the follicular antrum appears. Phospholipase C beta1 (PLC beta 1) is first exclusively localized to the nucleus and then migrates to the cytoplasm when the oocyte is fully grown. During oocyte maturation PLC beta 1 is active in the cytoplasm before it migrates and becomes active in the nucleus just prior to germinal vesicle breakdown. Because a similar circuit is observed for protein kinase C alpha (PKC alpha), PKC beta 1, PKC beta 2, and active mitogen-activated protein kinase, it is tempting to envisage that a feedback loop occurs between these pathways as demonstrated in other cell types. The chronology of these molecular movements into the oocyte reveals the particular and important role of the nucleus phosphoinositide cycle during oocyte meiosis. It appears also that this chronology is crucial and that defects leading to an inappropriate intracellular localization can have dramatic consequences. Such anomalies can prevent the production of competent oocytes and lead to fertility problems.     

Body mass index, blood pressure, and risk of depression in the elderly: a marginal structural model

The authors' objective was to investigate the associations of body mass index (BMI; weight (kg)/height (m)(2)) and blood pressure with the risk of developing depression in a large sample of elderly French participants (aged ≥65 years) followed for 10 years (Dijon portion of the Three-City Study, 1999-2010). Depression was defined as either having major depressive symptoms according to the Mini-International Neuropsychiatric Interview or taking antidepressant medication. The authors fitted marginal structural models to examine the relations of BMI and blood pressure with depression. Among subjects who were depression-free at baseline (n = 3,090), 478 developed incident depression over 10 years of follow-up. The analyses showed that after baseline values and time-dependent confounders were controlled, subjects with high BMI at follow-up had an increased adjusted risk of developing depression compared with subjects with normal BMI (risk ratio = 1.60, 95% confidence interval: 1.03, 2.51). Compared with subjects with normal blood pressure, those with high blood pressure were not at increased risk of incident depression, whereas those with low blood pressure had a higher risk of developing depression. These findings provide some epidemiologic support for implication of lifestyle risk factors in the development of depression in the elderly. Future studies should focus on evaluating lifestyle and obesity interventions among the elderly.