Lymphangiogenesis and angiogenesis during human fetal pancreas development

Background: The complex endocrine and exocrine functionality of the human pancreas depends on an efficient fluid transport through the blood and the lymphatic vascular systems. The lymphatic vasculature has key roles in the physiology of the pancreas and in regulating the immune response, both important for developing successful transplantation and cell-replacement therapies to treat diabetes. However, little is known about how the lymphatic and blood systems develop in humans. Here, we investigated the establishment of these two vascular systems in human pancreas organogenesis in order to understand neovascularization in the context of emerging regenerative therapies. Methods: We examined angiogenesis and lymphangiogenesis during human pancreas development between 9 and 22 weeks of gestation (W9-W22) by immunohistochemistry. Results: As early as W9, the peri-pancreatic mesenchyme was populated by CD31-expressing blood vessels as well as LYVE1- and PDPN-expressing lymphatic vessels. The appearance of smooth muscle cell-coated blood vessels in the intra-pancreatic mesenchyme occurred only several weeks later and from W14.5 onwards the islets of Langerhans also became heavily irrigated by blood vessels. In contrast to blood vessels, LYVE1- and PDPN-expressing lymphatic vessels were restricted to the peri-pancreatic mesenchyme until later in development (W14.5-W17), and some of these invading lymphatic vessels contained smooth muscle cells at W17. Interestingly, between W11-W22, most large caliber lymphatic vessels were lined with a characteristic, discontinuous, collagen type IV-rich basement membrane. Whilst lymphatic vessels did not directly intrude the islets of Langerhans, three-dimensional reconstruction revealed that they were present in the vicinity of islets of Langerhans between W17-W22. Conclusion: Our data suggest that the blood and lymphatic machinery in the human pancreas is in place to support endocrine function from W17-W22 onwards. Our study provides the first systematic assessment of the progression of lymphangiogenesis during human pancreatic development

Dedicated bifurcation analysis: basic principles

Over the last several years significant interest has arisen in bifurcation stenting, in particular stimulated by the European Bifurcation Club. Traditional straight vessel analysis by QCA does not satisfy the requirements for such complex morphologies anymore. To come up with practical solutions, we have developed two models, a Y-shape and a T-shape model, suitable for bifurcation QCA analysis depending on the specific anatomy of the coronary bifurcation. The principles of these models are described in this paper, as well as the results of validation studies carried out on clinical materials. It can be concluded that the accuracy, precision and applicability of these new bifurcation analyses are conform the general guidelines that have been set many years ago for conventional QCA-analyses

Inhalation characteristics of asthma patients, COPD patients and healthy volunteers with the Spiromax® and Turbuhaler® devices: a randomised, cross-over study.

BACKGROUND: Spiromax® is a novel dry-powder inhaler containing formulations of budesonide plus formoterol (BF). The device is intended to provide dose equivalence with enhanced user-friendliness compared to BF Turbuhaler® in asthma and chronic obstructive pulmonary disease (COPD). The present study was performed to compare inhalation parameters with empty versions of the two devices, and to investigate the effects of enhanced training designed to encourage faster inhalation. METHODS: This randomised, open-label, cross-over study included children with asthma (n = 23), adolescents with asthma (n = 27), adults with asthma (n = 50), adults with COPD (n = 50) and healthy adult volunteers (n = 50). Inhalation manoeuvres were recorded with each device after training with the patient information leaflet (PIL) and after enhanced training using an In-Check Dial device. RESULTS: After PIL training, peak inspiratory flow (PIF), maximum change in pressure (∆P) and the inhalation volume (IV) were significantly higher with Spiromax than with the Turbuhaler device (p values were at least <0.05 in all patient groups). After enhanced training, numerically or significantly higher values for PIF, ∆P, IV and acceleration remained with Spiromax versus Turbuhaler, except for ∆P in COPD patients. After PIL training, one adult asthma patient and one COPD patient inhaled <30 L/min through the Spiromax compared to one adult asthma patient and five COPD patients with the Turbuhaler. All patients achieved PIF values of at least 30 L/min after enhanced training. CONCLUSIONS: The two inhalers have similar resistance so inhalation flows and pressure changes would be expected to be similar. The higher flow-related values noted for Spiromax versus Turbuhaler after PIL training suggest that Spiromax might have human factor advantages in real-world use. After enhanced training, the flow-related differences between devices persisted; increased flow rates were achieved with both devices, and all patients achieved the minimal flow required for adequate drug delivery. Enhanced training could be useful, especially in COPD patients

Generalized approach to translating exercise tests and prescribing exercise

Although there is evidence supporting the benefit of regular exercise, and recommendations about exercise and physical activity, the process of individually prescribing exercise following exercise testing is more difficult. Guidelines like % heart rate (HR) reserve (HRR) require an anchoring maximal test and do not always provide a homogenous training experience. When prescribing HR on the basis of % HRR, rating of perceived exertion or Talk Test, cardiovascular/perceptual drift during sustained exercise makes prescription of the actual workload difficult. To overcome this issue, we have demonstrated a strategy for "translating" exercise test responses to steady state exercise training on the basis of % HRR or the Talk Test that appeared adequate for individuals ranging from cardiac patients to athletes. However, these methods depended on the nature of the exercise test details. In this viewpoint, we combine these data with workload expressed as Metabolic Equivalent Task (METs). We demonstrate that there is a regular stepdown between the METs during training to achieve the same degree of homeostatic disturbance during testing. The relationship was linear, was highly-correlated (r = 0.89), and averaged 71.8% (Training METs/Test METs). We conclude that it appears possible to generate a generalized approach to correctly translate exercise test responses to exercise training

New approaches for the assessment of vessel sizes in quantitative (cardio-)vascular X-ray analysis

This paper presents new approaches for the assessment of the arterial and reference diameters in (cardio-)vascular X-ray images, designed to overcome the problems experienced in conventional quantitative coronary and vascular angiography approaches. In single or “straight” vessel segments, the arterial and reference diameter directions were made independent of each other in order to be able to measure the minimal lumen diameter (MLD) more accurately, especially in curved vessel segments. For ostial segments, an extension of this approach was used, to allow measurement of ostial lesions in sidebranches more proximal than using conventional methods. Furthermore, two new bifurcation approaches were developed. The validation study shows that the straight segment approach results in significant smaller MLDs (on average 0.032 mm) and the ostial approach achieves on average an increase in %DS of 3.8% and an increase in lesion length of 0.59 mm due to loosening the directional constraint. The validation of our new bifurcation approaches in phantom data as well as clinical data shows only small differences between pre- and post-intervention measurements of the reference diameters outside the bifurcation core (errors smaller than 0.06 mm) and the bifurcation core area (errors smaller than 1.4% for phantom data). In summary, these new approaches have led to further improvements in the quantitative analyses of (cardio-)vascular X-ray angiographies

Work at night and breast cancer - report on evidence-based options for preventive actions

In 2007, the International Agency for Research on Cancer classified shift work involving circadian disruption as probably carcinogenic to humans (group 2A), primarily based on experimental and epidemiologic evidence for breast cancer. In order to examine options for evidence-based preventive actions, 16 researchers in basic, epidemiological and applied sciences convened at a workshop in Copenhagen 26-27 October 2011. This paper summarizes the evidence from epidemiological and experimental studies and presents possible recommendations for prevention of the effects of night work on breast cancer. Among those studies that quantified duration of shift work, there were statistically significant elevations in risk only after about 20 years working night shift. It is unclear from these studies whether or not there is a modest but real elevated risk for shorter durations. Hence, restriction of the total number of years working night shift could be one future preventive recommendation for shift workers. The diurnal secretion of melatonin by the pineal gland with peak in secretory activity durin Work during the night is widespread worldwide. To provide additional evidence-based recommendations on prevention of diseases related to night shift work, large studies on the impact of various shift schedules and type of light on circadian rhythms need to be conducted in real work environments

Differential Impact of a Dutch Alcohol Prevention Program Targeting Adolescents and Parents Separately and Simultaneously: Low Self-Control and Lenient Parenting at Baseline Predict Effectiveness

To test whether baseline levels of the factors accountable for the impact of the Prevention of Alcohol use in Students (PAS) intervention (self-control, perceived rules about alcohol and parental attitudes about alcohol), moderate the effect of the intervention. A cluster randomized trial including 3,490 Dutch early adolescents (M age = 12.66, SD = 0.49) and their parents randomized over four conditions: 1) parent intervention, 2) student intervention, 3) combined intervention and 4) control group. Moderators at baseline were used to examine the differential effects of the interventions on onset of (heavy) weekly drinking at 34-month follow-up. The combined intervention was only effective in preventing weekly drinking among those adolescents who reported to have lower self-control and more lenient parents at baseline. No differential effect was found for the onset of heavy weekly drinking. No moderating roles of self-control and lenient parenting were found for the separate student and parent interventions regarding the onset of drinking. The combined intervention is more effective among adolescents with low-self control and lenient parents at baseline, both factors that were a specific target of the intervention. The relevance of targeting self-control in adolescents and restrictive parenting is underlined