Postpartum hemorrhage (PPH) is the most common cause of maternal mortality worldwide. Predicting PPH remains difficult, and risk factors vary among populations. We aimed to determine prevalence, risk ...factors, and causes for PPH in our obstetric population in South-Central Louisiana.
We conducted a retrospective cohort study utilizing medical records for deliveries between October 2015 and September 2020 at Woman's Hospital, a tertiary hospital in South-Central Louisiana. PPH was defined by the current American College of Obstetricians and Gynecologists' (ACOG) criteria as cumulative blood loss greater than or equal to 1000 mL within 24 h after the birth process regardless of route of delivery. Logistic regression assessed the association of PPH and possible risk factors: anemia at the time of delivery, race, parity, delivery mode, body mass index, age, and health insurance. An additional logistic regression also investigated risk factors within our cohort for severe maternal morbidity among patients who experienced PPH including the same covariates.
A total of 30,674 deliveries were included in our cohort, among which PPH occurred in 12.3% (n = 3773). Patients experiencing PPH were more likely to be of Black race, Medicaid-eligible, deliver via cesarean section, and have lower hemoglobin and hematocrit at time of delivery compared to patients without PPH (all p < .001). Anemia at delivery (aOR = 1.28; 95%CI = 1.154-1.419), cesarean delivery (aOR = 8.796; 95%CI = 7.731-10.007), BMI > 40kg/m
2
(aOR = 1.363; 95%CI = 1.186-1.567), and Black race (aOR = 1.233; 95%CI = 1.099-1.383) were the strongest predictors of PPH. Among cesarean cases (n = 10,888), Black race and BMI > 40 kg/m
2
were the strongest predictors for PPH. Among patients who experienced PPH, anemia was associated with a higher likelihood of experiencing a severe maternal morbidity event (aOR = 2.587; 95%CI = 1.990-3.364).
Consistent with literature in the United States, Black race, increased BMI, cesarean delivery, and anemia were associated with risk of PPH. Anemia at delivery increased the risk for severe maternal morbidity among patients experiencing PPH.
Quorum sensing is an intercellular signaling mechanism that enables bacterial cells to coordinate population‐level behaviors. How quorum sensing functions in natural habitats remains poorly ...understood. Vibrio fischeri is a bacterial symbiont of the Hawaiian bobtail squid Euprymna scolopes and depends on LuxI/LuxR quorum sensing to produce the symbiotic trait of bioluminescence. A previous study demonstrated that animals emit light when co‐colonized by a Δlux mutant, which lacks several genes within the lux operon that are necessary for bioluminescence production, and a LuxI− mutant, which cannot synthesize the quorum signaling molecule N‐3‐oxohexanoyl‐homoserine lactone. Here, we build upon that observation and show that populations of LuxI− feature elevated promoter activity for the lux operon. We find that population structures comprising of Δlux and LuxI− are attenuated within the squid, but a wild‐type strain enables the LuxI− strain type to be maintained in vivo. These experimental results support a model of interpopulation signaling, which provides basic insight into how quorum sensing functions within the natural habitats found within a host.
CD23 is a glycan-binding receptor in some mammalian species Jégouzo, Sabine A.F.; Feinberg, Hadar; Morrison, Andrew G. ...
Journal of biological chemistry/The Journal of biological chemistry,
10/2019, Letnik:
294, Številka:
41
Journal Article
Recenzirano
Odprti dostop
CD23, the low-affinity IgE receptor found on B lymphocytes and other cells, contains a C-terminal lectin-like domain that resembles C-type carbohydrate-recognition domains (CRDs) found in many ...glycan-binding receptors. In most mammalian species, the CD23 residues required to form a sugar-binding site are present, although binding of CD23 to IgE does not involve sugars. Solid-phase binding competition assays, glycoprotein blotting experiments, and glycan array analysis employing the lectin-like domains of cow and mouse CD23 demonstrate that they bind to mannose, GlcNAc, glucose, and fucose and to glycoproteins that bear these sugars in nonreducing terminal positions. Crystal structures of the cow CRD in the presence of α-methyl mannoside and GlcNAcβ1–2Man reveal that a range of oligosaccharide ligands can be accommodated in an open binding site in which most interactions are with a single terminal sugar residue. Although mouse CD23 shows a pattern of monosaccharide and glycoprotein binding similar to cow CD23, the binding is weaker. In contrast, no sugar binding was observed in similar experiments with human CD23. The absence of sugar-binding activity correlates with accumulation of mutations in the gene for CD23 in the primate lineage leading to humans, resulting in loss of key sugar-binding residues. These results are consistent with a role for CD23 in many species as a receptor for potentially pathogenic microorganisms as well as IgE. However, the ability of CD23 to bind several different ligands varies between species, suggesting that it has distinct functions in different organisms.
Pleural mesothelioma is an aggressive malignancy with limited effective therapies. In order to identify therapeutic targets, we integrated SNP genotyping, sequencing and transcriptomics from tumours ...and low-passage patient-derived cells. Previously unrecognised deletions of SUFU locus (10q24.32), observed in 21% of 118 tumours, resulted in disordered expression of transcripts from Hedgehog pathways and the T-cell synapse including VISTA. Co-deletion of Interferon Type I genes and CDKN2A was present in half of tumours and was a predictor of poor survival. We also found previously unrecognised deletions in RB1 in 26% of cases and show sub-micromolar responses to downstream PLK1, CHEK1 and Aurora Kinase inhibitors in primary mesothelioma cells. Defects in Hippo pathways that included RASSF7 amplification and NF2 or LATS1/2 mutations were present in 50% of tumours and were accompanied by micromolar responses to the YAP1 inhibitor Verteporfin. Our results suggest new therapeutic avenues in mesothelioma and indicate targets and biomarkers for immunotherapy.
Accurately predicting the Indian monsoon is limited by inadequate understanding of the underlying processes, which feed into systematic model biases. Here we aim to understand the dynamic and ...thermodynamic features associated with the progression of the monsoon, using 2016 as a representative year, with the help of convection‐permitting simulations of the Met Office Unified Model. Simulations are carried out in a 4 km resolution limited‐area model, nested within a coarser global model. Two major processes thought to influence the northwestward progression of the monsoon are: (a) the interaction between the low‐level monsoon flow and a mid‐tropospheric dry‐air intrusion from the northwest, and (b) land–atmosphere interactions. We find that the 4 km limited‐area model simulates the mid‐tropospheric moistening that erodes the northwesterly dry intrusion, pushing the northern limit of moist convection northwestwards. The surface soil moisture also plays a major role at the leading edge of the monsoon progression. The heavy rains associated with the local onset wet the soil, reducing the sensitivity of surface fluxes to soil moisture and weakening the land influence on further progression of monsoon rains. The 4 km model is tested with an alternative land‐surface configuration to explore its sensitivity to land‐surface processes. We find that the choice of soil and vegetation ancillaries affects the time‐scales of soil moisture–precipitation feedback and the timing of diurnal convection, thereby affecting the local onset. We further compare these simulations with a parametrized convection run at 17 km resolution to isolate the effects of convective parametrization and resolution. The model with explicit convection better simulates the dynamic and thermodynamic features associated with the progression of the monsoon.
Time evolution of (a) 3‐day mean rainfall (blue lines), and the spatial correlation between 3‐day antecedent rains and 0630 UTC (1200 IST) evaporative fraction (red lines), and (b) area‐mean sensible heat flux (H, red lines) and spatial standard deviation of the sensible heat flux (blue lines) from the two 4 km simulations with IGBP and CCI land ancillaries at 0630 UTC (1200 IST) over the monsoon core zone. The grey vertical lines separate the months May, June and July.
Variable levels of gene expression between tissues complicates the use of RNA sequencing of patient biosamples to delineate the impact of genomic variants. Here, we describe a gene- and ...tissue-specific metric to inform the feasibility of RNA sequencing. This overcomes limitations of using expression values alone as a metric to predict RNA-sequencing utility. We have derived a metric, minimum required sequencing depth (MRSD), that estimates the depth of sequencing required from RNA sequencing to achieve user-specified sequencing coverage of a gene, transcript, or group of genes. We applied MRSD across four human biosamples: whole blood, lymphoblastoid cell lines (LCLs), skeletal muscle, and cultured fibroblasts. MRSD has high precision (90.1%–98.2%) and overcomes transcript region-specific sequencing biases. Applying MRSD scoring to established disease gene panels shows that fibroblasts, of these four biosamples, are the optimum source of RNA for 63.1% of gene panels. Using this approach, up to 67.8% of the variants of uncertain significance in ClinVar that are predicted to impact splicing could be assayed by RNA sequencing in at least one of the biosamples. We demonstrate the utility and benefits of MRSD as a metric to inform functional assessment of splicing aberrations, in particular in the context of Mendelian genetic disorders to improve diagnostic yield.
Determining the life-history consequences for fishes living in extreme and variable environments will be vital in predicting the likely impacts of ongoing climate change on reef fish demography. ...Here, we compare size-at-age and maximum body size of two common reef fish species (
Lutjanus ehrenbergii
and
Pomacanthus maculosus
) between the environmentally extreme Arabian/Persian Gulf (‘Arabian Gulf’) and adjacent comparably benign Oman Sea. Additionally, we use otolith increment width profiles to investigate the influence of temperature, salinity and productivity on the individual growth rates. Individuals of both species showed smaller size-at-age and lower maximum size in the Arabian Gulf compared to conspecifics in the less extreme and less variable environment of the Oman Sea, suggesting a life-history trade-off between size and metabolic demands. Salinity was the best environmental predictor of interannual growth across species and regions, with low growth corresponding to more saline conditions. However, salinity had a weaker negative effect on interannual growth of fishes in the Arabian Gulf than in the Oman Sea, indicating Arabian Gulf populations may be better able to acclimate to changing environmental conditions. Temperature had a weak positive effect on the interannual growth of fishes in the Arabian Gulf, suggesting that these populations may still be living within their thermal windows. Our results highlight the potential importance of osmoregulatory cost in impacting growth, and the need to consider the effect of multiple stressors when investigating the consequences of future climate change on fish demography.
Background:
The purpose of this article was to review the basic science pertaining to the harmful effects of cigarette smoke, summarize recent clinical outcome studies, and examine the benefits of ...smoking cessation and the efficacy of current smoking cessation strategies.
Methods:
The literature concerning basic science, clinical outcomes, and smoking cessation was reviewed; over half (56%) of the 52 articles reviewed were published in the last 5 years.
Results:
Smoking is associated with low bone mineral density, delayed fracture union, peri-implant bone loss, and implant failure. Orthopedic surgical patients who smoke have increased pain and lower overall patient satisfaction, along with significantly increased rates of wound healing complications.
Discussion/Conclusion:
Active smoking is a significant modifiable risk factor and should be discontinued before foot and ankle surgery whenever possible. Orthopedic surgeons play an important role in educating patients on the effects of smoking and facilitating access to smoking cessation resources.
Level of Evidence:
Level V, expert opinion.
Key message
The
Brassica napus
Illumina array provides genome-wide markers linked to the available genome sequence, a significant tool for genetic analyses of the allotetraploid
B. napus
and its ...progenitor diploid genomes.
A high-density single nucleotide polymorphism (SNP) Illumina Infinium array, containing 52,157 markers, was developed for the allotetraploid
Brassica napus
. A stringent selection process employing the short probe sequence for each SNP assay was used to limit the majority of the selected markers to those represented a minimum number of times across the highly replicated genome. As a result approximately 60 % of the SNP assays display genome-specificity, resolving as three clearly separated clusters (AA, AB, and BB) when tested with a diverse range of
B. napus
material. This genome specificity was supported by the analysis of the diploid ancestors of
B. napus,
whereby 26,504 and 29,720 markers were scorable in
B. oleracea
and
B. rapa
, respectively. Forty-four percent of the assayed loci on the array were genetically mapped in a single doubled-haploid
B. napus
population allowing alignment of their physical and genetic coordinates. Although strong conservation of the two positions was shown, at least 3 % of the loci were genetically mapped to a homoeologous position compared to their presumed physical position in the respective genome, underlying the importance of genetic corroboration of locus identity. In addition, the alignments identified multiple rearrangements between the diploid and tetraploid Brassica genomes. Although mostly attributed to genome assembly errors, some are likely evidence of rearrangements that occurred since the hybridisation of the progenitor genomes in the
B. napus
nucleus. Based on estimates for linkage disequilibrium decay, the array is a valuable tool for genetic fine mapping and genome-wide association studies in
B. napus
and its progenitor genomes.
Deregulation of KRAS4b signaling pathway has been implicated in 30% of all cancers. Membrane localization of KRAS4b is an essential step for the initiation of the downstream signaling cascades that ...guide various cellular mechanisms. KRAS4b plasma membrane (PM) binding is mediated by the insertion of a prenylated moiety that is attached to the terminal carboxy-methylated cysteine, in addition to electrostatic interactions of its positively charged hypervariable region with anionic lipids. Calmodulin (CaM) has been suggested to selectively bind KRAS4b to act as a negative regulator of the RAS/mitogen-activated protein kinase (MAPK) signaling pathway by displacing KRAS4b from the membrane. However, the mechanism by which CaM can recognize and displace KRAS4b from the membrane is not well understood. In this study, we employed biophysical and structural techniques to characterize this mechanism in detail. We show that KRAS4b prenylation is required for binding to CaM and that the hydrophobic pockets of CaM can accommodate the prenylated region of KRAS4b, which might represent a novel CaM-binding motif. Remarkably, prenylated KRAS4b forms a 2:1 stoichiometric complex with CaM in a nucleotide-independent manner. The interaction between prenylated KRAS4b and CaM is enthalpically driven, and electrostatic interactions also contribute to the formation of the complex. The prenylated KRAS4b terminal KSKTKC-farnesylation and carboxy-methylation is sufficient for binding and defines the minimal CaM-binding motif. This is the same region implicated in membrane and phosphodiesterase6-δ binding. Finally, we provide a structure-based docking model by which CaM binds to prenylated KRAS4b. Our data provide new insights into the KRAS4b-CaM interaction and suggest a possible mechanism whereby CaM can regulate KRAS4b membrane localization.
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