SerpinB1 protects the mature neutrophil reserve in the bone marrow

SerpinB1 is among the most efficient inhibitors of neutrophil serine proteases--NE, CG, and PR-3--and we investigated here its role in neutrophil development and homeostasis. We found that serpinB1 is expressed in all human bone marrow leukocytes, including stem and progenitor cells. Expression levels were highest in the neutrophil lineage and peaked at the promyelocyte stage, coincident with the production and packaging of the target proteases. Neutrophil numbers were decreased substantially in the bone marrow of serpinB1(-/-) mice. This cellular deficit was associated with an increase in serum G-CSF levels. On induction of acute pulmonary injury, neutrophils were recruited to the lungs, causing the bone marrow reserve pool to be completely exhausted in serpinB1(-/-) mice. Numbers of myeloid progenitors were normal in serpinB1(-/-) bone marrow, coincident with the absence of target protease expression at these developmental stages. Maturation arrest of serpinB1(-/-) neutrophils was excluded by the normal CFU-G growth in vitro and the normal expression in mature neutrophils of early and late differentiation markers. Normal absolute numbers of proliferating neutrophils and pulse-chase kinetic studies in vivo showed that the bone marrow deficit in serpinB1(-/-) mice was largely restricted to mature, postmitotic neutrophils. Finally, upon overnight culture, apoptosis and necrosis were greater in purified bone marrow neutrophils from serpinB1(-/-) compared with WT mice. Collectively, these findings demonstrate that serpinB1 sustains a healthy neutrophil reserve that is required in acute immune responses.

The impact of social presence on team performance in social networking platforms

Next to the extensive use of social networking platforms (SNPs) for communication and relationship building with friends and relatives, SNPs are also increasingly used for enhancing collaboration at work. SNP usage at the workplace is fundamentally different and it is unclear how SNPs can improve collaboration as well as in what way their designs should be modified and adapted to collaboration settings. This research identifies specific SNP functions that enhance social presence as particularly beneficial for collaboration. Consequently, two designs of SNPs, one with high social presence and one with low social presence, are outlined and its impacts on collaboration are discussed. A framework is constructed that illustrates how social presence in SNPs can improve team performance through enhancing transactive memory within teams (intra-group collaboration) and relational capital across teams (inter-group collaboration). In addition, it is outlined how this framework could be evaluated in an experimental setting of teams working on a complex group task.

Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease

The preferred initial treatment for patients with stable coronary artery disease is the best available medical therapy. We hypothesized that in patients with functionally significant stenoses, as determined by measurement of fractional flow reserve (FFR), percutaneous coronary intervention (PCI) plus the best available medical therapy would be superior to the best available medical therapy alone.

Reduced pretreatment ovarian reserve in premenopausal female patients with Hodgkin lymphoma or non-Hodgkin-lymphoma--evaluation by using antimüllerian hormone and retrieved oocytes

To study whether the ovarian reserve in female lymphoma patients is already reduced before the start of chemotherapy.

Does the beta-blocker nebivolol increase coronary flow reserve?

INTRODUCTION: Nebivolol, a highly selective beta1-adrenergic receptor-blocker, increases basal and stimulated endothelial nitric oxide (NO)-release. It is unknown, whether coronary perfusion is improved by the increase in NO availability. Therefore, we sought to evaluate the effect of nebivolol on coronary flow reserve (CFR) and collateral flow. METHODS: Doppler-flow wire derived coronary flow velocity measurements were obtained in ten controls and eight patients with coronary artery disease (CAD) at rest and after intracoronary nebivolol. CFR was defined as maximal flow during adenosine-induced hyperemia divided by resting flow. In the CAD group, collateral flow was determined after dilatation of a flow-limiting coronary stenosis. Collateral flow index (CFI) was defined as the ratio of flow velocity during balloon inflation divided by resting flow. RESULTS: CFR at rest was 3.0+/-0.6 in controls and 2.1+/-0.4 in CAD patients. After intracoronary doses of 0.1, 0.25, and 0.5 mg nebivolol, CFR increased to 3.4+/-0.7, 3.9+/-0.9, and 4.0+/-0.1 (p<0.01) in controls, and to 2.3+/-0.7, 2.6+/-0.9, and 2.6+/-0.5 (p<0.05) in CAD patients. CFI decreased significantly with intracoronary nebivolol and correlated to changes in heart rate (r=0.75, p<0.001) and rate-pressure product (r=0.59, p=0.001). DISCUSSION: Intracoronary nebivolol is associated with a significant increase in CFR due to reduction in resting flow (controls), or due to an increase in maximal coronary flow (CAD patients). CFI decreased with nebivolol parallel to the reduction in myocardial oxygen consumption.