Docosahexaenoic acid supplementation during pregnancy as phospholipids did not improve the incorporation of this fatty acid into rat fetal brain compared with the triglyceride form

Prenatal docosahexaenoic acid (DHA) supply is important to ensure an adequate infant neurodevelopment. Several fat supplements with DHA under different chemical structures are available. There is an increased placental phospholipase activity at the end of pregnancy. The hypothesis of this study was to discern whether DHA consumption during pregnancy as phospholipids (PLs) could be more available for placental DHA uptake and fetal accretion than triglycerides (TGs) form. We aimed to evaluate maternofetal DHA status in pregnant rats fed with DHA as PL from egg yolk or TG from algae oil to determine which source might be most effective during pregnancy. Three experimental diets were tested: 2.5% DHA-TG (n = 10), 2.5% DHA-PL (n = 9), and 9% DHA-PL (n = 9). The total PL content of these diets was 2%, 12%, and 38%, respectively. We determined dietary fat absorption and quantified fatty acids by gas chromatography in maternal and fetal tissues. Dietary PL enhanced significantly dietary fat absorption. However, animals fed the highest PL-content diet (38% PL and 9% DHA-PL) stored most of the absorbed fat in maternal liver, promoting hepatic steatosis, which was not observed in the lower PL-content diets (12% and 2%). Despite higher fat absorption of PL-containing diets, maternal and fetal tissues (including fetal brain) did not show major differences in DHA content between the 2.5% DHA-PL and 2.5% DHA-TG–fed groups. We conclude that the chemical form of DHA consumed by the rat during gestation (PL or TG) does not differentially affect DHA accretion into fetal brain, and both lipid sources can be equally used for maternal DHA supplementation during pregnancy.     

Pertactin-negative variants of Bordetella pertussis in New York State: A retrospective analysis, 2004–2013

The first report of pertactin-negative variants of Bordetella pertussis in the United States has raised questions about the role of acellular pertussis vaccines in the recent increase of pertussis cases. Our laboratory utilized a sequence-based method to identify mutations in the pertactin gene responsible for these variants and assessed vaccination status from the associated cases.     

Multidrug-resistant Acinetobacter baumannii infections: Current evidence on treatment options and the role of pharmacokinetics/pharmacodynamics in dose optimisation

Acinetobacter baumannii remains a difficult-to-treat pathogen that poses a significant challenge to clinicians and costs to the healthcare system. There is a lack of clinical efficacy data to aid in the selection of optimal treatment for multidrug-resistant (MDR) A. baumannii infections. This paper aimed to review recent literature on the treatment of MDR A. baumannii infections and novel agents in the pipeline and to discuss the clinical data supporting their use. Colistin has been widely studied as monotherapy or as part of combination therapy, but its use is limited due to nephrotoxicity. The clinical benefit of combination therapy, whether empirical or targeted, has yet to be demonstrated owing to a lack of definitive evidence from randomised controlled trials (RCTs). Most available clinical studies are retrospective and lack control groups, which offers low-grade evidence. Novel agents such as cefiderocol, plazomicin, eravacycline and sulbactam/ETX2514 combination are promising options for the treatment of different infectious pathologies caused by MDR A. baumannii, but these have yet to be evaluated in RCTs. A better understanding of the pharmacokinetics/pharmacodynamics of the ‘old’ antibiotics is required to optimise their dosing regimens in order to maximise bacterial killing, minimise toxicities and improve clinical outcomes.     

Suppression of macrophage-mediated phagocytosis of apoptotic cells by soluble β-glucan due to a failure of PKC-βII translocation

If apoptotic cells are not removed efficiently, they may proceed to the stage of secondary necrosis, which would cause inflammation. Therefore, identification of cause(s) and agent(s) for down-modulating phagocytosis of apoptotic cells would help understand the pathologies. In this study we found that macrophage-mediated phagocytosis of apoptotic cells was suppressed by both soluble and particulate β-glucan. This suppression was not observed when secondary necrotic cells were used. The adhesion of apoptotic cells to macrophages was not suppressed by soluble β-glucan, suggesting that soluble β-glucan suppresses phagocytosis at a post-adhesion step. Experiments involving PKC inhibitors suggested that PKC-βII is required for phagocytosis of apoptotic cells but not secondary necrotic ones by macrophages. Translocation of GFP-PKC-βII from the cytoplasm to membranes occurred upon interaction with apoptotic cells but not secondary necrotic ones. Such translocation was inhibited by soluble β-glucan. Overall, this study suggests that suppression of macrophage-mediated phagocytosis of apoptotic cells by soluble β-glucan is due to a failure of PKC-βII translocation.     

Effect of sclerostin antibody treatment in a mouse model of severe osteogenesis imperfecta

Osteogenesis imperfecta (OI) is a heritable bone fragility disorder that is usually caused by mutations affecting collagen type I production in osteoblasts. Stimulation of bone formation through sclerostin antibody treatment (Sost-ab) has shown promising results in mouse models of relatively mild OI. We assessed the effect of once-weekly intravenous Sost-ab injections for 4 weeks in male Col1a1^Jrt/+ mice, a model of severe dominant OI, starting either at 4 weeks (growing mice) or at 20 weeks (adult mice) of age. Sost-ab had no effect on weight or femur length. In OI mice, no significant treatment-associated differences in serum markers of bone formation (alkaline phosphatase activity, procollagen type I N-propeptide) or resorption (C-telopeptide of collagen type I) were found. Micro-CT analyses at the femur showed that Sost-ab treatment was associated with higher trabecular bone volume and higher cortical thickness in wild type mice at both ages and in growing OI mice, but not in adult OI mice. Three-point bending tests of the femur showed that in wild type but not in OI mice, Sost-ab was associated with higher ultimate load and work to failure. Quantitative backscattered electron imaging of the femur did not show any effect of Sost-ab on CaPeak (the most frequently occurring calcium concentration in the bone mineral density distribution), regardless of genotype, age or measurement location. Thus, Sost-ab had a larger effect in wild type than in Col1a1^Jrt/+ mice. Previous studies had found marked improvements of Sost-ab on bone mass and strength in an OI mouse model with a milder phenotype. Our data therefore suggest that Sost-ab is less effective in a more severely affected OI mouse model.     

Social support and depression of adults with visual impairments

Relatively little research exists with regard to the relationship between social support and depression among adults with visual impairments. Such a gap is noteworthy when one considers that individuals become more dependent on others as they enter middle and late adulthood. The present research will examine the association between social networks, social support and depression among adults with visual impairments. Seventy-seven adults with visual impairments participated in the study. Depression, social network and emotional/practical social support were measured with self-report measures. Additionally, the degree to which emotional/practical social support received were positive or negative and the ability of respondents to self-manage their daily living were assessed. Less than a third of respondents scored above the threshold for depressive symptoms. Depressive symptoms were not related to gender or vision status. Depression was correlated with age, educational level, less positive practical support, more negative practical support and more negative emotional support, with lower perceptions of self-management representing the most robust predictor of depression. Age moderated the relationship between depression and self-management, and between depression and negative emotional support. Lower perceptions of self-management and negative emotional support were significantly associated with depressive symptoms.     

CCN4/WISP-1 positively regulates chondrogenesis by controlling TGF-β3 function

The CCN family of proteins plays important roles in development and homeostasis of bone and cartilage. To understand the role of CCN4 in chondrogenesis, human bone marrow stromal cells (hBMSCs) were transduced with CCN4 adenovirus (adCCN4) or siRNA to CCN4 (siCCN4) in the presence or absence of transforming growth factor-β3 (TGF-β3). Overexpression of CCN4 enhanced TGF-β3-induced SMAD2/3 phosphorylation and chondrogenesis of hBMSCs in an in vitro assay using a micromass culture model. On the other hand, knockdown of CCN4 inhibited the TGF-β3-induced SMAD2/3 phosphorylation and synthesis of cartilage matrix in micromass cultures of hBMSCs. Immunoprecipitation–western blot analysis revealed that CCN4 bound to TGF-β3 and regulated the ability of TGF-β3 to bind to hBMSCs. In vivo analysis confirmed there was a significant decrease in the gene expression levels of chondrocyte markers in cartilage samples from Ccn4-knock out (KO) mice, compared to those from wild type (WT) control. In order to investigate the regenerative properties of the articular cartilage in Ccn4-KO mice, articular cartilage defects were surgically performed in the knee joints of young mice, and the results showed that the cartilage was partially repaired in WT mice, but not in Ccn4-KO mice. In conclusion, these results show, for the first time, that CCN4 has a positive influence on chondrogenic differentiation by modulating the effects of TGF-β3.