Changes in dermal matrix in the absence of Rac1 in keratinocytes

Keratinocytes, in response to irritants, secrete pro‐inflammatory mediators which recruit and activate immune and mesenchymal cells, including fibroblasts, to repair the skin. Fibroblasts respond by synthesising collagen and promoting the crosslinking extracellular matrix (ECM). We recently showed that the deletion of Rac1 in keratinocytes causes heightened inflammation due to aberrant crosstalk with immune cells. Indeed, the skin of these mice shows a higher inflammatory response to the induction of irritant contact dermatitis (ICD), and also even to treatment with a vehicle alone, compared with controls. As inflammation is intimately linked with fibrotic disease in the skin, this raised the question as to whether this deletion may also affect the deposition and arrangement of the dermal ECM. This study assessed the effects of Rac1 deletion in keratinocytes and of the heightened inflammatory status by induction of ICD on the tissue localisation and arrangements of dermal collagen. Qualitative analysis did not reveal evidence for the formation of pathologies in the dermis. However, quantitative analysis did reveal some perturbations in the dermal matrix, namely that only the combination of the lack of Rac1 and ICD affects the architectural organisation of the dermal collagen, and that a higher inflammatory state in the tissue (i.e. when Rac1 is deleted in the keratinocytes or ICD is induced in the skin, or a combination of both) influences the diameter of the collagen fibrils. It is proposed that this increase in the diameter of collagen fibrils due to inflammation may serve as pre‐fibrotic marker enabling earlier determination of fibrosis and earlier treatment. This study has revealed previously unknown effects on the ECM due to the deletion of Rac1 in keratinocytes.     

European birth cohorts for environmental health research

Background: Many pregnancy and birth cohort studies investigate the health effects of early-life environmental contaminant exposure. An overview of existing studies and their data is needed to improve collaboration, harmonization, and future project planning.Objectives: Our goal was to create a comprehensive overview of European birth cohorts with environmental exposure data.Methods: Birth cohort studies were included if they a) collected data on at least one environmental exposure, b) started enrollment during pregnancy or at birth, c) included at least one follow-up point after birth, d) included at least 200 mother–child pairs, and e) were based in a European country. A questionnaire collected information on basic protocol details and exposure and health outcome assessments, including specific contaminants, methods and samples, timing, and number of subjects. A full inventory can be searched on www.birthcohortsenrieco.net.Results: Questionnaires were completed by 37 cohort studies of > 350,000 mother–child pairs in 19 European countries. Only three cohorts did not participate. All cohorts collected biological specimens of children or parents. Many cohorts collected information on passive smoking (n = 36), maternal occupation (n = 33), outdoor air pollution (n = 27), and allergens/biological organisms (n = 27). Fewer cohorts (n = 12–19) collected information on water contamination, ionizing or nonionizing radiation exposures, noise, metals, persistent organic pollutants, or other pollutants. All cohorts have information on birth outcomes; nearly all on asthma, allergies, childhood growth and obesity; and 26 collected information on child neurodevelopment.Conclusion: Combining forces in this field will yield more efficient and conclusive studies and ultimately improve causal inference. This impressive resource of existing birth cohort data could form the basis for longer-term and worldwide coordination of research on environment and child health.     

Activity Dose Reduction in 64Cu-DOTATATE PET in Patients with Neuroendocrine Neoplasms: Impact on Image Quality and Lesion Detection Ability

Molecular Imaging and Biology - Patients with neuroendocrine neoplasms (NEN) engage in lifelong follow-up with frequent somatostatin receptor PET, e.g. [64Cu]Cu-DOTATATE PET, and continued measures...     

Evaluation of ECG-gated [<Superscript>11</Superscript>C]acetate PET for measuring left ventricular volumes,mass, and myocardial external efficiency

Background

Noninvasive estimation of myocardial external efficiency (MEE) requires measurements of left ventricular (LV) oxygen consumption with [¹¹C]acetate PET in addition to LV stroke volume and mass with cardiovascular magnetic resonance (CMR). Measuring LV geometry directly from ECG-gated [¹¹C]acetate PET might enable MEE evaluation from a single PET scan. Therefore, we sought to establish the accuracy of measuring LV volumes, mass, and MEE directly from ECG-gated [¹¹C]acetate PET.

Methods

Thirty-five subjects with aortic valve stenosis underwent ECG-gated [¹¹C]acetate PET and CMR. List mode PET data were rebinned into 16-bin ECG-gated uptake images before measuring LV volumes and mass using commercial software and compared to CMR. Dynamic datasets were used for calculation of mean LV oxygen consumption and MEE.

Results

LV mass, volumes, and ejection fraction measured by CMR and PET correlated strongly (r = 0.86-0.92, P < .001 for all), but were underestimated by PET (P < .001 for all except ESV P = .79). PET-based MEE, corrected for bias, correlated fairly with PET/CMR-based MEE (r = 0.60, P < .001, bias ?3 ± 21%, P = .56). PET-based MEE bias was strongly associated with LV wall thickness.

Conclusions

Although analysis-related improvements in accuracy are recommended, LV geometry estimated from ECG-gated [¹¹C]acetate PET correlate excellently with CMR and can indeed be used to evaluate MEE.

     

Self-monitoring of cardiac autonomic function at home is feasible

Background

Cardiovascular autonomic neuropathy (CAN) is associated with diabetes and may be related to the development of hypertension, ischemic stroke, and a number of other late complications. The earliest sign of CAN is a reduction of heart rate variability (HRV). Standard HRV tests for CAN include expiration-to-inspiration ratio, response to active standing (30:15), and the Valsalva maneuver. Because of the technical requirements for these tests, they are limited to the point-of-care office or a clinical laboratory setting. It is unknown if a “white-coat“ phenomenon exists in autonomic neuropathy testing and if home testing is feasible. The aims of this study were (1) to evaluate the reproducibility of CAN testing in a clinical setting, (2) to evaluate the feasibility of self-monitoring of cardiovascular autonomic function at home, and (3) report possible differences in measurements taken at the hospital versus those taken at home.

Method

Ten healthy subjects were included. Participants underwent in-hospital testing for CAN before and after home monitoring. For 6 consecutive days, participants measured autonomic function once a day at home. The intra- and interindividual reproducibility was determined by coefficient of variation (CV) and the reproducibility coefficient (RC). Agreement between hospital and home testing was analyzed using Pearson r, mean difference, and Bland–Altman analysis with Pitman’s test of difference in variance.

Results

Pitman’s test showed no significant difference in variance between hospital and home measurements, indicating suitable agreement between the two measurements. Reproducibility was moderate to high in all measures, with RC ranging from 66–94% and CV ranging from 5–10%.

Conclusions

Home testing of CAN is feasible. The evaluations showed no significant systematic error of in-hospital testing compared with self-monitoring at home. In this study, we were not able to demonstrate the presses of “white coat” effect in standard cardiovascular reflex tests.