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Abstract-The aim of the present study was to elucidate how transforming growth factor-␤ 1 (TGF-␤ 1 ) can stimulate collagen deposition in cardiac tissue by interstitial cells via stimulation of fibroblasts, via myofibroblasts, or via differentiation of fibroblasts to myofibroblasts. The dose-and time-dependent stimulation of collagen production and of expression of ␣-smooth muscle actin (␣-SMA), a marker of myofibroblasts, was studied in cultures of second-passage adult rat cardiac fibroblasts. The TGF-␤ 1 -stimulated collagen production is positively correlated (rϭ0.68, PϽ0.001) with the appearance of ␣-SMA. Only at high concentrations (40 to 600 pmol/L) and after a long time (24 to 48 hours) of incubation, TGF-␤ 1 increases the collagen production and stimulates the differentiation of fibroblasts to myofibroblasts. The maximal stimulation of the collagen production (2-fold, PϽ0.001) observed after incubation of cultures of fibroblasts with 600 pmol/L TGF-␤ 1 for 48 hours is accompanied by a maximal stimulation of ␣-SMA expression (3.5-fold, PϽ0.001), when cultures consist mainly of myofibroblasts. The stimulation of collagen production cannot be reversed either after additional incubation of TGF-␤ 1 -stimulated second-passage cultures for 2 days or in their offspring in the next third passage after incubation for 7 days without TGF-␤ 1 . The increased collagen production in these third-passage cultures cannot be further stimulated by TGF-␤ 1 . Our data suggest that TGF-␤ 1 -stimulated collagen production in cultures of adult rat cardiac ventricular fibroblasts cannot be explained by a direct stimulation of the collagen production either in fibroblasts or in myofibroblasts. Instead, TGF-␤ 1 induces the differentiation of fibroblasts to myofibroblasts, which have a higher activity for collagen production than fibroblasts.

The D allele is not associated with hypertension, but behaves as a marker of atherosclerotic cardiovascular complications and diabetic nephropathy. These associations do not necessarily imply a causal relationship and may have been inflated by publication bias. Nevertheless, their possible therapeutic implications may be subject to further investigation in prospective (intervention) studies.

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Background Maternal infections are an important cause of maternal mortality and severe maternal morbidity. We report the main findings of the WHO Global Maternal Sepsis Study, which aimed to assess the frequency of maternal infections in health facilities, according to maternal characteristics and outcomes, and coverage of core practices for early identification and management.Methods We did a facility-based, prospective, 1-week inception cohort study in 713 health facilities providing obstetric, midwifery, or abortion care, or where women could be admitted because of complications of pregnancy, childbirth, post-partum, or post-abortion, in 52 low-income and middle-income countries (LMICs) and high-income countries (HICs). We obtained data from hospital records for all pregnant or recently pregnant women hospitalised with suspected or confirmed infection. We calculated ratios of infection and infection-related severe maternal outcomes (ie, death or near-miss) per 1000 livebirths and the proportion of intrahospital fatalities across country income groups, as well as the distribution of demographic, obstetric, clinical characteristics and outcomes, and coverage of a set of core practices for identification and management across infection severity groups.