Outcomes associated with planned place of birth among women with low-risk pregnancies

Background:Previous studies have shown that planned home birth is associated with a decreased likelihood of intrapartum intervention with no difference in neonatal outcomes compared with planned hospital birth. The purpose of our study was to evaluate different birth settings by comparing neonatal mortality, morbidity and rates of birth interventions between planned home and planned hospital births in Ontario, Canada.Methods:We used a provincial database of all midwifery-booked pregnancies between 2006 and 2009 to compare women who planned home birth at the onset of labour to a matched cohort of women with low-risk pregnancies who had planned hospital births attended by midwives. We conducted subgroup analyses by parity. Our primary outcome was stillbirth, neonatal death (< 28 d) or serious morbidity (Apgar score < 4 at 5 min or resuscitation with positive pressure ventilation and cardiac compressions).Results:We compared 11 493 planned home births and 11 493 planned hospital births. The risk of our primary outcome did not differ significantly by planned place of birth (relative risk [RR] 1.03, 95% confidence interval [CI] 0.68–1.55). These findings held true for both nulliparous (RR 1.04, 95% CI 0.62–1.73) and multiparous women (RR 1.00, 95% CI 0.49–2.05). All intrapartum interventions were lower among planned home births.Interpretation:Compared with planned hospital birth, planned home birth attended by midwives in a jurisdiction where home birth is well-integrated into the health care system was not associated with a difference in serious adverse neonatal outcomes but was associated with fewer intrapartum interventions.In Ontario, Canada, the College of Midwives of Ontario has regulated midwifery since 1994, and increasing numbers of women with low obstetrical risk and their newborns receive care in a publicly funded, midwifery-led continuity of care model.¹ Midwives have admission and discharge privileges at their local hospitals and are able to consult or transfer care to other health care providers if required. In Ontario, midwives attend a small proportion of all births in the province (10%), and about 20% of the births they attend take place at home.² A comprehensive record is maintained for every woman and infant in a midwife’s care. Until 2009, this record was submitted to the provincial Ministry of Health and Long-term Care (MOHLTC) through the Ontario Midwifery Program to access reimbursement for care provided.In the last century, Western culture has come to view hospital birth as safer than home birth.³ Recently, however, the value of hospital birth for all women with low-risk pregnancies has come into question; it has been suggested that in the absence of benefit, a planned hospital birth for this population may increase the use of intrapartum interventions, including cesarean delivery.^4–7 Even though recent studies comparing planned home and hospital births have had moderate sample sizes, they are individually limited in their ability to report definitively on rare outcomes such as death. Owing to a lack of evidence from randomized controlled trials (RCTs) to show that restricting a woman’s freedom to choose a place of birth prevents harm, the authors of a 2012 Cochrane review of planned hospital versus planned home births concluded that home birth services with collaborative medical backup should be established and offered to women with low-risk pregnancies in all jurisdictions.⁸ This conclusion, along with findings from the large English Birthplace Cohort Study,⁴ may be what prompted the National Institute for Health and Care Excellence (NICE) in England to update its intrapartum care guidelines to recommend that, for women at low risk of birth-associated complications, home birth should be considered a generally safe option.⁹ With the paucity of information derived from RCTs,⁸ observational studies are essential to continue to inform and monitor maternal and infant outcomes for women at low obstetrical risk who plan home or hospital birth, and to continue to provide pregnant women with quality information about choice of birthplace.The primary purpose of this retrospective cohort study was to determine the risk of stillbirth or neonatal death or serious neonatal morbidity among women at low obstetrical risk whose deliveries were attended by midwives and who had planned a home birth at the onset of labour, compared with women at low obstetrical risk who planned a hospital birth at the onset of labour. In addition, we also compared the incidence of maternal death and morbidity, birth interventions and breastfeeding between planned home births and planned hospital births.     

Physical and chemical mutagens improved Sporotrichum thermophile,strain ST20 for enhanced Phytase activity

ObjectivePhosphorous is an essential micronutrient of plants and involved in critical biological functions. In nature, phosphorous is mostly present in immobilized inorganic mineral and in the fixed organic form including phytic acid and phosphoesteric compounds. However, the bioavailability of bound phosphorous could be enhanced by the use of phosphate solubilizing microorganisms such as bacteria and fungi. The phytases are widespread in an environment and have been isolated from different sources comprising bacteria and fungi.MethodologyIn current studies, we show the successful use of gamma rays and EMS (Ethyl Methane Sulphonate) mutagenesis for enhanced activity of phytases in a fungal strain Sporotrichum thermophile.ResultsWe report an improved strain ST2 that could produce a clear halo zone around the colony, up to 24 mm. The maximum enzymatic activity was found of 382 U/mL on pH 5.5. However, the phytase activity was improved to 387 U/ml at 45 °C. We also report that the mutants produced through EMS showed the greater potential for phytase production.ConclusionThe current study highlights the potential of EMS mutagenesis for strain improvement over physical mutagens.     

Extremely stable indole-3-glycerol-phosphate synthase from hyperthermophilic archaeon Pyrococcus furiosus

Extremophiles - The gene-encoding Indole-3-glycerol phosphate synthase, a key enzyme involved in the cyclization of 1-(o-carboxyphenylamino)-1-deoxyribulose 5-phosphate, from Pyrococcus furiosus...     

Effect of obesity on high-density lipoprotein metabolism

Reduced levels of high-density lipoproteins (HDL) in non-obese and obese states are associated with increased risk for the development of coronary artery disease. Therefore, it is imperative to determine the mechanisms responsible for reduced HDL in obese states and, conversely, to examine therapies aimed at increasing HDL levels in these individuals. This paper examines the multiple causes for reduced HDL in obese states and the effect of exercise and diet--two non-pharmacologic therapies--on HDL metabolism in humans. In general, the concentration of HDL-cholesterol is adversely altered in obesity, with HDL-cholesterol levels associated with both the degree and distribution of obesity. More specifically, intra-abdominal visceral fat deposition is an important negative correlate of HDL-cholesterol. The specific subfractions of HDL that are altered in obese states include the HDL2, apolipoprotein A-I, and pre-beta1 subfractions. Decreased HDL levels in obesity have been attributed to both an enhancement in the uptake of HDL2 by adipocytes and an increase in the catabolism of apolipoprotein A-I on HDL particles. In addition, there is a decrease in the conversion of the pre-beta1 subfraction, the initial acceptor of cholesterol from peripheral cells, to pre-beta2 particles. Conversely, as a means of reversing the decrease in HDL levels in obesity, sustained weight loss is an effective method. More specifically, weight loss achieved through exercise is more effective at raising HDL levels than dieting. Exercise mediates positive effects on HDL levels at least partly through changes in enzymes of HDL metabolism. Increased lipid transfer to HDL by lipoprotein lipase and reduced HDL clearance by hepatic triglyceride lipase as a result of endurance training are two important mechanisms for increases in HDL observed from exercise.     

Glycation of low-density lipoprotein results in the time-dependent accumulation of cholesteryl esters and apolipoprotein B-100 protein in primary human monocyte-derived macrophages

Nonenzymatic covalent binding (glycation) of reactive aldehydes (from glucose or metabolic processes) to low-density lipoproteins has been previously shown to result in lipid accumulation in a murine macrophage cell line. The formation of such lipid-laden cells is a hallmark of atherosclerosis. In this study, we characterize lipid accumulation in primary human monocyte-derived macrophages, which are cells of immediate relevance to human atherosclerosis, on exposure to low-density lipoprotein glycated using methylglyoxal or glycolaldehyde. The time course of cellular uptake of low-density lipoprotein-derived lipids and protein has been characterized, together with the subsequent turnover of the modified apolipoprotein B-100 (apoB) protein. Cholesterol and cholesteryl ester accumulation occurs within 24 h of exposure to glycated low-density lipoprotein, and increases in a time-dependent manner. Higher cellular cholesteryl ester levels were detected with glycolaldehyde-modified low-density lipoprotein than with methylglyoxal-modified low-density lipoprotein. Uptake was significantly decreased by fucoidin (an inhibitor of scavenger receptor SR-A) and a mAb to CD36. Human monocyte-derived macrophages endocytosed and degraded significantly more (125)I-labeled apoB from glycolaldehyde-modified than from methylglyoxal-modified, or control, low-density lipoprotein. Differences in the endocytic and degradation rates resulted in net intracellular accumulation of modified apoB from glycolaldehyde-modified low-density lipoprotein. Accumulation of lipid therefore parallels increased endocytosis and, to a lesser extent, degradation of apoB in human macrophages exposed to glycolaldehyde-modified low-density lipoprotein. This accumulation of cholesteryl esters and modified protein from glycated low-density lipoprotein may contribute to cellular dysfunction and the increased atherosclerosis observed in people with diabetes, and other pathologies linked to exposure to reactive carbonyls.     

Widespread colonisation of Tanzanian catchments by introduced Oreochromis tilapia fishes: the legacy from decades of deliberate introduction

From the 1950s onwards, programmes to promote aquaculture and improve capture fisheries in East Africa have relied heavily on the promise held by introduced species. In Tanzania these introductions have been poorly documented. Here we report the findings of surveys of inland water bodies across Tanzania between 2011 and 2017 that clarify distributions of tilapiine cichlids of the genus Oreochromis. We identified Oreochromis from 123 sampling locations, including 14 taxa restricted to their native range and three species that have established populations beyond their native range. Of these three species, the only exotic species found was blue-spotted tilapia (Oreochromis leucostictus), while Nile tilapia (Oreochromis niloticus) and Singida tilapia (Oreochromis esculentus), which are both naturally found within the country of Tanzania, have been translocated beyond their native range. Using our records, we developed models of suitable habitat for the introduced species based on recent (1960–1990) and projected (2050, 2070) East African climate. These models indicated that presence of suitable habitat for these introduced species will persist and potentially expand across the region. The clarification of distributions provided here can help inform the monitoring and management of biodiversity, and inform policy related to the future role of introduced species in fisheries and aquaculture.

     

Effects of the isothiocyanate sulforaphane on TGF-β1-induced rat cardiac fibroblast activation and extracellular matrix interactions

An important step in many pathological conditions, particularly tissue and organ fibrosis, is the conversion of relatively quiescent cells into active myofibroblasts. These are highly specialized cells that participate in normal wound healing but also contribute to pathogenesis. These cells possess characteristics of smooth muscle cells and fibroblasts, have enhanced synthetic activity secreting abundant extracellular matrix components, cytokines, and growth factors, and are capable of generating contractile force. As such, these cells have become potential therapeutic targets in a number of disease settings. Transforming growth factor β (TGF-β) is a potent stimulus of fibrosis and myofibroblast formation and likewise is an important therapeutic target in several disease conditions. The plant-derived isothiocyanate sulforaphane has been shown to have protective effects in several pathological models including diabetic cardiomyopathy, carcinogenesis, and fibrosis. These studies suggest that sulforaphane may be an attractive preventive agent against disease progression, particularly in conditions involving alterations of the extracellular matrix and activation of myofibroblasts. However, few studies have evaluated the effects of sulforaphane on cardiac fibroblast activation and their interactions with the extracellular matrix. The present studies were carried out to determine the potential effects of sulforaphane on the conversion of quiescent cardiac fibroblasts to an activated myofibroblast phenotype and associated alterations in signaling, expression of extracellular matrix receptors, and cellular physiology following stimulation with TGF-β1. These studies demonstrate that sulforaphane attenuates TGF-β1-induced myofibroblast formation and contractile activity. Sulforaphane also reduces expression of collagen-binding integrins and inhibits canonical and noncanonical TGF-β signaling pathways.     

Dysregulated RNA polyadenylation contributes to metabolic impairment in non-alcoholic fatty liver disease

Pre-mRNA processing is an essential mechanism for the generation of mature mRNA and the regulation of gene expression in eukaryotic cells. While defects in pre-mRNA processing have been implicated in a number of diseases their involvement in metabolic pathologies is still unclear. Here, we show that both alternative splicing and alternative polyadenylation, two major steps in pre-mRNA processing, are significantly altered in non-alcoholic fatty liver disease (NAFLD). Moreover, we find that Serine and Arginine Rich Splicing Factor 10 (SRSF10) binding is enriched adjacent to consensus polyadenylation motifs and its expression is significantly decreased in NAFLD, suggesting a role mediating pre-mRNA dysregulation in this condition. Consistently, inactivation of SRSF10 in mouse and human hepatocytes in vitro, and in mouse liver in vivo, was found to dysregulate polyadenylation of key metabolic genes such as peroxisome proliferator-activated receptor alpha (PPARA) and exacerbate diet-induced metabolic dysfunction. Collectively our work implicates dysregulated pre-mRNA polyadenylation in obesity-induced liver disease and uncovers a novel role for SRSF10 in this process.     

The actin nucleator Spir-1 is a virus restriction factor that promotes innate immune signalling

Cellular proteins often have multiple and diverse functions. This is illustrated with protein Spir-1 that is an actin nucleator, but, as shown here, also functions to enhance innate immune signalling downstream of RNA sensing by RIG-I/MDA-5. In human and mouse cells lacking Spir-1, IRF3 and NF-κB-dependent gene activation is impaired, whereas Spir-1 overexpression enhanced IRF3 activation. Furthermore, the infectious virus titres and sizes of plaques formed by two viruses that are sensed by RIG-I, vaccinia virus (VACV) and Zika virus, are increased in Spir-1 KO cells. These observations demonstrate the biological importance of Spir-1 in the response to virus infection. Like cellular proteins, viral proteins also have multiple and diverse functions. Here, we also show that VACV virulence factor K7 binds directly to Spir-1 and that a diphenylalanine motif of Spir-1 is needed for this interaction and for Spir-1-mediated enhancement of IRF3 activation. Thus, Spir-1 is a new virus restriction factor and is targeted directly by an immunomodulatory viral protein that enhances virus virulence and diminishes the host antiviral responses.     

Early postnatal cardiac changes and premature death in transgenic mice overexpressing a mutant form of serum response factor

Serum response factor (SRF) is a key regulator of a number of extracellular signal-regulated genes important for cell growth and differentiation. A form of the SRF gene with a double mutation (dmSRF) was generated. This mutation reduced the binding activity of SRF protein to the serum response element and reduced the capability of SRF to activate the atrial natriuretic factor promoter that contains the serum response element. Cardiac-specific overexpression of dmSRF attenuated the total SRF binding activity and resulted in remarkable morphologic changes in the heart of the transgenic mice. These mice had dilated atrial and ventricular chambers, and their ventricular wall thicknesses were only 1/2 to 1/3 the thickness of that of nontransgenic mice. Also these mice had smaller cardiac myocytes and had less myofibrils in their myocytes relative to nontransgenic mice. Altered gene expression and slight interstitial fibrosis were observed in the myocardium of the transgenic mice. All the transgenic mice died within the first 12 days after birth, because of the early onset of severe, dilated cardiomyopathy. These results indicate that dmSRF overexpression in the heart apparently alters cardiac gene expression and blocks normal postnatal cardiac growth and development.