Crude and adjusted comparisons of cesarean delivery rates using the Robson classification: A population-based cohort study in Canada and Sweden, 2004 to 2016

BackgroundThe Robson classification has become a global standard for comparing and monitoring cesarean delivery (CD) rates across populations and over time; however, this classification does not account for differences in important maternal, fetal, and obstetric practice factors known to impact CD rates. The objectives of our study were to identify subgroups of women contributing to differences in the CD rate in Sweden and British Columbia (BC), Canada using the Robson classification and to estimate the contribution of maternal, fetal/infant, and obstetric practice factors to differences in CD rates between countries and over time.Methods and findingsWe conducted a population-based cohort study of deliveries in Sweden (January 1, 2004 to December 31, 2016; n = 1,392,779) and BC (March 1, 2004 to April 31, 2017; n = 559,205). Deliveries were stratified into Robson categories and the CD rate, relative size of each group and its contribution to the overall CD rate were compared between the Swedish and the Canadian cohorts. Poisson and log-binomial regression were used to assess the contribution of maternal, fetal, and obstetric practice factors to spatiotemporal differences in Robson group-specific CD rates between Sweden and BC.Nulliparous women comprised 44.8% of the study population, while women of advanced maternal age (≥35 years) and women with overweight/obesity (≥25 kg/m²) constituted 23.5% and 32.4% of the study population, respectively. The CD rate in Sweden was stable at approximately 17.0% from 2004 to 2016 (p for trend = 0.10), while the CD rate increased in BC from 29.4% to 33.9% (p for trend < 0.001). Differences in CD rates between Sweden and BC varied by Robson group, for example, in Group 1 (nullipara with a term, single, cephalic fetus with spontaneous labor), the CD rate was 8.1% in Sweden and 20.4% in BC (rate ratio [RR] for BC versus Sweden = 2.52, 95% confidence interval [CI] 2.49 to 2.56, p < 0.001) and in Group 2 (nullipara, single, cephalic fetus, term gestation with induction of labor or prelabor CD), the rate of CD was 37.3% in Sweden and 45.9% in BC (RR = 1.23, 95% CI 1.22 to 1.25, p < 0.001). The effect of adjustment for maternal characteristics (e.g., age, body mass index), maternal comorbidity (e.g., preeclampsia), fetal characteristics (e.g., head position), and obstetric practice factors (e.g., epidural) ranged from no effect (e.g., among breech deliveries; Groups 6 and 7) to explaining up to 5.2% of the absolute difference in the CD rate (Group 2: adjusted CD rate in BC 40.7%, adjusted RR = 1.09, 95% CI 1.08 to 1.12, p < 0.001). Adjustment also explained a substantial fraction of the temporal change in CD rates among some Robson groups in BC. Limitations of the study include a lack of information on intrapartum details, such as labor duration as well as maternal and perinatal outcomes associated with the observed differences in CD rates.ConclusionsIn this study, we found that several factors not included in the Robson classification explain a significant proportion of the spatiotemporal difference in CD rates in some Robson groups. These findings suggest that incorporating these factors into explanatory models using the Robson classification may be useful for ensuring that public health initiatives regarding CD rates are evidence informed.

Giulia Muraca and colleagues examine differences in the rates of cesarean delivery between British Columbia, Canada and Sweden over time using the Robson classification with and without adjusting for maternal, fetal/infant, and obstetric practice factors.     

Analysis of NCL Proteins from an Evolutionary Standpoint

The Neuronal Ceroid Lipofuscinoses (NCLs) are the most common group of neurodegenerative disorders of childhood. While mutations in eight different genes have been shown to be responsible for these clinically distinct types of NCL, the NCLs share many clinical and pathological similarities. We have conducted an exhaustive Basic Local Alignment Search Tool (BLAST) analysis of the human protein sequences for each of the eight known NCL proteins- CLN1, CLN2, CLN3, CLN5, CLN6, CLN7, CLN8 and CLN10. The number of homologous species per CLN-protein identified by BLAST searches varies depending on the parameters set for the BLAST search. For example, a lower threshold is able to pull up more homologous sequences whereas a higher threshold decreases this number. Nevertheless, the clade confines are consistent despite this variation in BLAST searching parameters. Further phylogenetic analyses on the appearance of NCL proteins through evolution reveals a different time line for the appearance of the CLN-proteins. Moreover, divergence of each protein shows a different pattern, providing important clues on the evolving role of these proteins. We present and review in-depth bioinformatic analysis of the NCL proteins and classify the CLN-proteins into families based on their structures and evolutionary relationships, respectively. Based on these analyses, we have grouped the CLN-proteins into common clades indicating a common evolving pathway within the evolutionary tree of life. CLN2 is grouped in Eubacteria, CLN1 and CLN10 in Viridiplantae, CLN3 in Fungi/ Metazoa, CLN7 in Bilateria and CLN5, CLN6 and CLN8 in Euteleostomi.     

Regulation of the Histone Deacetylase Hst3 by Cyclin-dependent Kinases and the Ubiquitin Ligase SCFCdc4

In Saccharomyces cerevisiae, histone H3 lysine 56 acetylation (H3K56ac) is a modification of new H3 molecules deposited throughout the genome during S-phase. H3K56ac is removed by the sirtuins Hst3 and Hst4 at later stages of the cell cycle. Previous studies indicated that regulated degradation of Hst3 plays an important role in the genome-wide waves of H3K56 acetylation and deacetylation that occur during each cell cycle. However, little is known regarding the mechanism of cell cycle-regulated Hst3 degradation. Here, we demonstrate that Hst3 instability in vivo is dependent upon the ubiquitin ligase SCF^Cdc4 and that Hst3 is phosphorylated at two Cdk1 sites, threonine 380 and threonine 384. This creates a diphosphorylated degron that is necessary for Hst3 polyubiquitylation by SCF^Cdc4. Mutation of the Hst3 diphospho-degron does not completely stabilize Hst3 in vivo, but it nonetheless results in a significant fitness defect that is particularly severe in mutant cells treated with the alkylating agent methyl methanesulfonate. Unexpectedly, we show that Hst3 can be degraded between G₂ and anaphase, a window of the cell cycle where Hst3 normally mediates genome-wide deacetylation of H3K56. Our results suggest an intricate coordination between Hst3 synthesis, genome-wide H3K56 deacetylation by Hst3, and cell cycle-regulated degradation of Hst3 by cyclin-dependent kinases and SCF^Cdc4.     

Downregulation of HDAC2 and HDAC3 via oleuropein as a potent prevention and therapeutic agent in MCF-7 breast cancer cells

Breast cancer is the most common malignancy in the world with the highest rate of morbidity and mortality. Due to the several side effects of chemotherapy and radiotherapy, recent studies have focused on the use of herbal medicines. Epidemiological reports have shown the inverse relationship between breast cancer risk and intake of olive. Oleuropein (OLE) is a polyphenolic compound in virgin olive oil with antineoplastic properties and it is well tolerated by humans. Recent reports have shown that OLE has effects on the control of cancer by modulating epigenetics, such as histone deacetylase (HDAC) inhibition. However, the epigenetic mechanisms of OLE anticancer properties are yet to be properly investigated. Therefore, this study aimed to determine the therapeutic effects of OLE through the modulation of histone deacetylase 2 (HDAC2) and histone deacetylase 3 (HDAC3) expression in breast cancer cell line. MCF-7 cells were tested with and without OLE, and also the cell viability, apoptosis, and migration were examined. HDAC2 and HDAC3 expression genes were assessed by quantitative real-time polymerase chain reaction. It was found that OLE decreased the expression of both HDAC2 and HDAC3 (P < 0.05), induced apoptosis and retarded cell migration and cell invasion in a dose-dependent manner (P < 0.05). These results showed that OLE is a potential therapeutic and preventive agent for breast cancer.     

A Disulfide Bond-forming Machine Is Linked to the Sortase-mediated Pilus Assembly Pathway in the Gram-positive Bacterium Actinomyces oris

Export of cell surface pilins in Gram-positive bacteria likely occurs by the translocation of unfolded precursor polypeptides; however, how the unfolded pilins gain their native conformation is presently unknown. Here, we present physiological studies to demonstrate that the FimA pilin of Actinomyces oris contains two disulfide bonds. Alanine substitution of cysteine residues forming the C-terminal disulfide bridge abrogates pilus assembly, in turn eliminating biofilm formation and polymicrobial interaction. Transposon mutagenesis of A. oris yielded a mutant defective in adherence to Streptococcus oralis, and revealed the essential role of a vitamin K epoxide reductase (VKOR) gene in pilus assembly. Targeted deletion of vkor results in the same defects, which are rescued by ectopic expression of VKOR, but not a mutant containing an alanine substitution in its conserved CXXC motif. Depletion of mdbA, which encodes a membrane-bound thiol-disulfide oxidoreductase, abrogates pilus assembly and alters cell morphology. Remarkably, overexpression of MdbA or a counterpart from Corynebacterium diphtheriae, rescues the Δvkor mutant. By alkylation assays, we demonstrate that VKOR is required for MdbA reoxidation. Furthermore, crystallographic studies reveal that A. oris MdbA harbors a thioredoxin-like fold with the conserved CXXC active site. Consistently, each MdbA enzyme catalyzes proper disulfide bond formation within FimA in vitro that requires the catalytic CXXC motif. Because the majority of signal peptide-containing proteins encoded by A. oris possess multiple Cys residues, we propose that MdbA and VKOR constitute a major folding machine for the secretome of this organism. This oxidative protein folding pathway may be a common feature in Actinobacteria.     

Central Opioidergic and Adrenergic systems Mediates Food Intake via α1, α2 and β2 Receptors in Neonatal Layer-Type Chicken

International Journal of Peptide Research and Therapeutics - The aim of the current study was to determine possible interaction of central Opioidergic and Adrenergic systems on food intake...     

Taxonomic position of a Chinese <Emphasis Type="Italic">Pleurotus</Emphasis> “Bai-Ling-Gu”: it belongs to <Emphasis Type="Italic">Pleurotus eryngii</Emphasis> (DC.: Fr.) Quél. and evolved independently in China

The Chinese Bai-Ling-Gu is a mushroom named Pleurotus eryngii var. tuoliensis C.J. Mou. This species has been identified as P. nebrodensis or P. eryngii var. nebrodensis. We examined its taxonomic position by analysis of mating, cultivation, and rDNA sequences, and concluded as follows. (1) Bai-Ling-Gu mated with P. eryngii var. eryngii, and the F₁ and F₂ formed fruit bodies. (2) Bai-Ling-Gu mated with P. eryngii var. ferulae, and the F₁ formed fruit bodies. (3) In the di-mon mating test, P. eryngii var. nebrodensis from Sicily mated with monokaryons of P. eryngii var. eryngii but mated hardly at all with those of Bai-Ling-Gu and P. eryngii var. ferulae. The di-mon mating pattern of Bai-Ling-Gu resembled those of P. eryngii var. ferulae. (4) The partial sequences of rDNA ITS1 and IGS1 from the epitype of P. nebrodensis were identical with those from P. eryngii var. nebrodensis from Sicily but differed from those from Bai-Ling-Gu. (5) The strains of P. eryngii var. eryngii and P. eryngii var. ferulae were in a group, the strains of P. eryngii var. nebrodensis from Sicily were in another group, and the strains of Bai-Ling-Gu were in the other group in both the phylogenetic trees based on the ITS1 and the IGS1 sequences. These results led to the conclusion that Bai-Ling-Gu is a variety of P. eryngii and evolved independently in China. It is satisfactory to identify Bai-Ling-Gu with P. eryngii var. tuoliensis C.J. Mou.