Milk Consumption and Mortality from All Causes,Cardiovascular Disease,and Cancer: A Systematic Review and Meta-Analysis

Results from epidemiological studies of milk consumption and mortality are inconsistent. We conducted a systematic review and meta-analysis of prospective studies assessing the association of non-fermented and fermented milk consumption with mortality from all causes, cardiovascular disease, and cancer. PubMed was searched until August 2015. A two-stage, random-effects, dose-response meta-analysis was used to combine study-specific results. Heterogeneity among studies was assessed with the I² statistic. During follow-up periods ranging from 4.1 to 25 years, 70,743 deaths occurred among 367,505 participants. The range of non-fermented and fermented milk consumption and the shape of the associations between milk consumption and mortality differed considerably between studies. There was substantial heterogeneity among studies of non-fermented milk consumption in relation to mortality from all causes (12 studies; I² = 94%), cardiovascular disease (five studies; I² = 93%), and cancer (four studies; I² = 75%) as well as among studies of fermented milk consumption and all-cause mortality (seven studies; I² = 88%). Thus, estimating pooled hazard ratios was not appropriate. Heterogeneity among studies was observed in most subgroups defined by sex, country, and study quality. In conclusion, we observed no consistent association between milk consumption and all-cause or cause-specific mortality.     

Role of TGFβ1 and WNT6 in FGF2 and BMP4-driven endothelial differentiation of murine embryonic stem cells

Embryonic stem cells (ES) are a valuable source of endothelial cells. By co-culturing ES cells with the stromal PA6 cells, the endothelial commitment can be achieved by adding exogenous FGF2 or BMP4. In this work, the molecular pathways that direct the differentiation of ES cells toward endothelium in response to FGF2 are evaluated and compared to those activated by BMP4. To this purpose the genes expression profiles of both ES/PA6 co-cultures and of pure cultures of PA6 cells were obtained by microarray technique at different time points. The bioinformatics processing of the data indicated TGFβ1 as the most represented upstream regulator in FGF2-induced endothelial commitment while WNT pathway as the most represented in BMP4-activated endothelial differentiation. Loss of function experiments were performed to validate the importance of TGFβ1 and WNT6 respectively in FGF2 and BMP4-induced endothelial differentiation. The loss of TGFβ1 expression significantly impaired the accomplishment of the endothelial commitment unless exogenous recombinant TGFβ1 was added to the culture medium. Similarly, silencing WNT6 expression partially affected the endothelial differentiation of the ES cells upon BMP4 stimulation. Such dysfunction was recovered by the addition of recombinant WNT6 to the culture medium. The ES/PA6 co-culture system recreates an in vitro complete microenvironment in which endothelial commitment is accomplished in response to alternative signals through different mechanisms. Given the importance of WNT and TGFβ1 in mediating the crosstalk between tumor and stromal cells this work adds new insights in the mechanism of tumor angiogenesis and of its possible inhibition.

     

Use of intravenous digital subtraction ventriculography in the evaluation of left ventricle volumes and ejection fraction

Although intravenous digital subtraction ventriculography (IDSV) is increasingly used to estimate end-diastolic left ventricular volume (EDV), end-systolic left ventricular volume (ESV) and left ventricular ejection fraction (EF), its ability to reproduce the precise estimates provided by left ventricle cineangiography (LVCA) and its role in clinical cardiology have not been unequivocally established. In 32 patients subjected to cardiac catheterization for a variety of cardiac disorders and a normal or reduced left ventricular function the EDV, ESV and EF provided by a 30 degrees right anterior oblique LVCA were compared with those provided by a 30 degrees right anterior oblique IDSV. The mean EDV, ESV and EF obtained by IDSV in the 32 patients were superimposable on those obtained by LVCA. The individual EDV, ESV and EF values provided by the two methods were all related in a close linear fashion. For EF the correlation coefficient was 0.98 and the 90% confidence interval of the mean difference between the two series of values was +/- 6.1%, i.e. +/- 10% error compared to the mean EF provided by LVCA. Thus IDSV is a reliable and not too invasive method for estimating left ventricle volumes and ejection fraction. It might provide serial estimations with a better assessment of the evolution of a patient's disease and the effect of treatment.     

Inhibition of influenza A virus replication by resveratrol

We have previously shown that the life cycles of several viruses are influenced by host-cell redox states. Reports of the antioxidant activities of the plant polyphenol resveratrol (RV) prompted us to investigate its effects on influenza virus replication in vitro and in vivo. We found that RV strongly inhibited the replication of influenza virus in MDCK cells but that this activity was not directly related to glutathione-mediated antioxidant activity. Rather, it involved the blockade of the nuclear-cytoplasmic translocation of viral ribonucleoproteins and reduced expression of late viral proteins seemingly related to the inhibition of protein kinase C activity and its dependent pathways. RV also significantly improved survival and decreased pulmonary viral titers in influenza virus-infected mice. No toxic effects were observed in vitro or in vivo. That RV acts by inhibiting a cellular, rather than a viral, function suggests that it could be a particularly valuable anti-influenza drug.     

Pegfilgrastim compared with filgrastim after autologous peripheral blood stem cell transplantation in patients with solid tumours and lymphomas

To evaluate the safety and efficacy of pegfilgrastim administered as haematological support after autologous peripheral blood stem cell transplantation, we compared 44 patients with solid tumours and lymphomas receiving a 6-mg single dose of pegfilgrastim on day +5 after transplantation to a historical control group of 25 patients receiving filgrastim 5 μg kg⁻¹ day⁻¹ starting on day +5. There were no significant differences in haematological recovery nor in the incidence and duration of neutropenic fever. Median duration of grade 4 neutropenia in the pegfilgrastim and filgrastim group was similar. The incidence of grade III–IV mucositis was lower in pegfilgrastim than in filgrastim group due to the significant difference observed among the patients with solid tumours (p = 0.00). The only adverse event considered to be cytokine related was mild to moderate bone pain occurring during haematological recovery. According to the present study design and taking into account the current prices in our institution, the cost of the two drugs was similar in both treatment groups. In conclusion, a single injection of pegfilgrastim administered at day +5 post-transplantation shows comparable safety and efficacy profiles to daily injections of filgrastim and may be cost effective. Alberto Ballestrero and Davide Boy contributed equally to this article.