The Usefulness of the APACHE II Score in Obstetric Critical Care: A Structured Review.

OBJECTIVE: To assess the performance of the Acute Physiology and Chronic Health Evaluation II (APACHE II) mortality prediction model in pregnant and recently pregnant women receiving critical care in low-, middle-, and high-income countries during the study period (1985-2015), using a structured literature review. DATA SOURCES: Ovid MEDLINE, Embase, Web of Science, and Evidence-Based Medicine Reviews, searched for articles published between 1985 and 2015. STUDY SELECTION: Twenty-five studies (24 publications), of which two were prospective, were included in the analyses. Ten studies were from high-income countries (HICs), and 15 were from low- and middle-income countries (LMICs). Median study duration and size were six years and 124 women, respectively. DATA SYNTHESIS: ICU admission complicates 0.48% of deliveries, and pregnant and recently pregnant women account for 1.49% of ICU admissions. One quarter were admitted while pregnant, three quarters of these for an obstetric indication and for a median of three days. The median APACHE II score was 10.9, with a median APACHE II-predicted mortality of 16.6%. Observed mortality was 4.6%, and the median standardized mortality ratio was 0.36 (interquartile range 0.23 to 0.73). The standardized mortality ratio was < 0.9 in 24 of 25 studies. Women in HICs were more frequently admitted with a medical comorbidity but were less likely to die than were women in LMICs. CONCLUSION: The APACHE II score consistently overestimates mortality risks for pregnant and recently pregnant women receiving critical care, whether they reside in HICs or LMICs. There is a need for a pregnancy-specific outcome prediction model for these women

Oral antihypertensive therapy for severe hypertension in pregnancy and postpartum: a systematic review.

BACKGROUND: Pregnant and postpartum women with severe hypertension are at increased risk of stroke and require blood pressure (BP) reduction. Parenteral antihypertensives have been most commonly studied, but oral agents would be ideal for use in busy and resource-constrained settings. OBJECTIVES: To review systematically, the effectiveness of oral antihypertensive agents for treatment of severe pregnancy/postpartum hypertension. SEARCH STRATEGY: A systematic search of MEDLINE, EMBASE and the Cochrane Library was performed. SELECTION CRITERIA: Randomised controlled trials in pregnancy and postpartum with at least one arm consisting of a single oral antihypertensive agent to treat systolic BP ≥ 160 mmHg and/or diastolic BP ≥ 110 mmHg. DATA COLLECTION AND ANALYSIS: Cochrane RevMan 5.1 was used to calculate relative risk (RR) and weighted mean difference by random effects. MAIN RESULTS: We identified 15 randomised controlled trials (915 women) in pregnancy and one postpartum trial. Most trials in pregnancy compared oral/sublingual nifedipine capsules (8-10 mg) with another agent, usually parenteral hydralazine or labetalol. Nifedipine achieved treatment success in most women, similar to hydralazine (84% with nifedipine; relative risk [RR] 1.07, 95% confidence interval [95% CI] 0.98-1.17) or labetalol (100% with nifedipine; RR 1.02, 95% CI 0.95-1.09). Less than 2% of women treated with nifedipine experienced hypotension. There were no differences in adverse maternal or fetal outcomes. Target BP was achieved ~ 50% of the time with oral labetalol (100 mg) or methyldopa (250 mg) (47% labetelol versus 56% methyldopa; RR 0.85 95% CI 0.54-1.33). CONCLUSIONS: Oral nifedipine, and possibly labetalol and methyldopa, are suitable options for treatment of severe hypertension in pregnancy/postpartum

The effect of hypertensive disorders in pregnancy on small for gestational age and stillbirth: a population based study

BACKGROUND: Hypertensive disorders in pregnancy are leading causes of maternal, fetal and neonatal morbidity and mortality worldwide. However, studies attempting to quantify the effect of hypertension on adverse perinatal outcomes have been mostly conducted in tertiary centres. This population-based study explored the frequency of hypertensive disorders in pregnancy and the associated increase in small for gestational age (SGA) and stillbirth. METHODS: We used information on all pregnant women and births, in the Canadian province of Nova Scotia, between 1988 and 2000. Pregnancies were excluded if delivery occurred < 20 weeks, if birthweight was < 500 grams, if there was a high-order multiple pregnancy (greater than twin gestation), or a major fetal anomaly. RESULTS: The study population included 135,466 pregnancies. Of these, 7.7% had mild pregnancy-induced hypertension (PIH), 1.3% had severe PIH, 0.2% had HELLP (hemolysis, elevated liver enzymes, low platelets), 0.02% had eclampsia, 0.6% had chronic hypertension, and 0.4% had chronic hypertension with superimposed PIH. Women with any hypertension in pregnancy were 1.6 (95% CI 1.5–1.6) times more likely to have a live birth with SGA and 1.4 (95% CI 1.1–1.8) times more likely to have a stillbirth as compared with normotensive women. Adjusted analyses showed that women with gestational hypertension without proteinuria (mild PIH) and with proteinuria (severe PIH, HELLP, or eclampsia) were more likely to have infants with SGA (RR 1.5, 95% CI 1.4–1.6 and RR 3.2, 95% CI 2.8–3.6, respectively). Women with pre-existing hypertension were also more likely to give birth to an infant with SGA (RR 2.5, 95% CI 2.2–3.0) or to have a stillbirth (RR 3.2, 95% CI 1.9–5.4). CONCLUSIONS: This large, population-based study confirms and quantifies the magnitude of the excess risk of small for gestational age and stillbirth among births to women with hypertensive disease in pregnancy

Errors in the measurement of voltage-activated ion channels in cell-attached patch-clamp recordings

Patch-clamp recording techniques have revolutionized understanding of the function and sub-cellular location of ion channels in excitable cells. The cell-attached patch-clamp configuration represents the method of choice to describe the endogenous properties of voltage-activated ion channels in the axonal, somatic and dendritic membrane of neurons, without disturbance of the intracellular milieu. Here, we directly examine the errors associated with cell-attached patch-clamp measurement of ensemble ion channel activity. We find for a number of classes of voltage-activated channels, recorded from the soma and dendrites of neurons in acute brain-slices and isolated cells, that the amplitude and kinetics of ensemble ion channel activity recorded in cell-attached patches is significantly distorted by transmembrane voltage changes generated by the flow of current through the activated ion channels. We outline simple error–correction procedures that allow a more accurate description of the density and properties of voltage-activated channels to be incorporated into computational models of neurons

Longitudinal associations between television in the bedroom and body fatness in a UK cohort study.

OBJECTIVE: To assess longitudinal associations between screen-based media use (television (TV) and computer hours, having a TV in the bedroom) and body fatness among UK children. METHODS: Participants were 12 556 children from the UK Millennium Cohort Study who were followed from age 7 to age 11 years. Associations were assessed between screen-based media use and the following outcomes: body mass index (BMI), fat mass index (FMI), and overweight. RESULTS: In fully adjusted models, having a bedroom TV at age 7 years was associated with significantly higher BMI and FMI (excess BMI for boys=0.29, 95% confidence interval (CI) 0.06-0.52; excess BMI for girls=0.57, 95% CI 0.31-0.84; excess FMI for boys=0.20, 95% CI 0.04-0.37; excess FMI for girls=0.39, 95% CI 0.21-0.57) and increased risk of being overweight (relative risk (RR) for boys=1.21, 95% CI 1.07-1.36; RR for girls=1.31, 95% CI 1.15-1.48) at age 11 years, compared with having no bedroom TV. Hours spent watching TV or digital versatile disks were associated with increased risk of overweight among girls only. Computer use at age 7 years was not related to later body fatness for either gender. CONCLUSION: Having a TV in the child's bedroom was an independent risk factor for overweight and increased body fatness in this nationally representative sample of UK children. Childhood obesity prevention strategies should consider TVs in children's bedrooms as a risk factor for obesity.International Journal of Obesity advance online publication, 27 June 2017; doi:10.1038/ijo.2017.129

The home environment and childhood obesity in low-income households: indirect effects via sleep duration and screen time

Background Childhood obesity disproportionally affects children from low-income households. With the aim of informing interventions, this study examined pathways through which the physical and social home environment may promote childhood overweight/obesity in low-income households. Methods Data on health behaviors and the home environment were collected at home visits in low-income, urban households with either only normal weight (n = 48) or predominantly overweight/obese (n = 55) children aged 6–13 years. Research staff conducted comprehensive, in-person audits of the foods, media, and sports equipment in each household. Anthropometric measurements were collected, and children’s physical activity was assessed through accelerometry. Caregivers and children jointly reported on child sleep duration, screen time, and dietary intake of foods previously implicated in childhood obesity risk. Path analysis was used to test direct and indirect associations between the home environment and child weight status via the health behaviors assessed. Results Sleep duration was the only health behavior associated with child weight status (OR = 0.45, 95% CI: 0.27, 0.77), with normal weight children sleeping 33.3 minutes/day longer on average than overweight/obese children. The best-fitting path model explained 26% of variance in child weight status, and included paths linking chaos in the home environment, lower caregiver screen time monitoring, inconsistent implementation of bedtime routines, and the presence of a television in children’s bedrooms to childhood overweight/obesity through effects on screen time and sleep duration. Conclusions This study adds to the existing literature by identifying aspects of the home environment that influence childhood weight status via indirect effects on screen time and sleep duration in children from low-income households. Pediatric weight management interventions for low-income households may be improved by targeting aspects of the physical and social home environment associated with sleep

Type-specific dendritic integration in mouse retinal ganglion cells

Neural computation relies on the integration of synaptic inputs across a neuron’s dendritic arbour. However, it is far from understood how different cell types tune this process to establish cell-type specific computations. Here, using two-photon imaging of dendritic Ca2+ signals, electrical recordings of somatic voltage and biophysical modelling, we demonstrate that four morphologically distinct types of mouse retinal ganglion cells with overlapping excitatory synaptic input (transient Off alpha, transient Off mini, sustained Off, and F-mini Off) exhibit type-specific dendritic integration profiles: in contrast to the other types, dendrites of transient Off alpha cells were spatially independent, with little receptive field overlap. The temporal correlation of dendritic signals varied also extensively, with the highest and lowest correlation in transient Off mini and transient Off alpha cells, respectively. We show that differences between cell types can likely be explained by differences in backpropagation efficiency, arising from the specific combinations of dendritic morphology and ion channel densities

SOX9 Governs Differentiation Stage-Specific Gene Expression in Growth Plate Chondrocytes via Direct Concomitant Transactivation and Repression

Cartilage and endochondral bone development require SOX9 activity to regulate chondrogenesis, chondrocyte proliferation, and transition to a non-mitotic hypertrophic state. The restricted and reciprocal expression of the collagen X gene, Col10a1, in hypertrophic chondrocytes and Sox9 in immature chondrocytes epitomise the precise spatiotemporal control of gene expression as chondrocytes progress through phases of differentiation, but how this is achieved is not clear. Here, we have identified a regulatory element upstream of Col10a1 that enhances its expression in hypertrophic chondrocytes in vivo. In immature chondrocytes, where Col10a1 is not expressed, SOX9 interacts with a conserved sequence within this element that is analogous to that within the intronic enhancer of the collagen II gene Col2a1, the known transactivation target of SOX9. By analysing a series of Col10a1 reporter genes in transgenic mice, we show that the SOX9 binding consensus in this element is required to repress expression of the transgene in non-hypertrophic chondrocytes. Forced ectopic Sox9 expression in hypertrophic chondrocytes in vitro and in mice resulted in down-regulation of Col10a1. Mutation of a binding consensus motif for GLI transcription factors, which are the effectors of Indian hedgehog signaling, close to the SOX9 site in the Col10a1 regulatory element, also derepressed transgene expression in non-hypertrophic chondrocytes. GLI2 and GLI3 bound to the Col10a1 regulatory element but not to the enhancer of Col2a1. In addition to Col10a1, paired SOX9–GLI binding motifs are present in the conserved non-coding regions of several genes that are preferentially expressed in hypertrophic chondrocytes and the occurrence of pairing is unlikely to be by chance. We propose a regulatory paradigm whereby direct concomitant positive and negative transcriptional control by SOX9 ensures differentiation phase-specific gene expression in chondrocytes. Discrimination between these opposing modes of transcriptional control by SOX9 may be mediated by cooperation with different partners such as GLI factors

The evolution of the plastid chromosome in land plants: gene content, gene order, gene function

This review bridges functional and evolutionary aspects of plastid chromosome architecture in land plants and their putative ancestors. We provide an overview on the structure and composition of the plastid genome of land plants as well as the functions of its genes in an explicit phylogenetic and evolutionary context. We will discuss the architecture of land plant plastid chromosomes, including gene content and synteny across land plants. Moreover, we will explore the functions and roles of plastid encoded genes in metabolism and their evolutionary importance regarding gene retention and conservation. We suggest that the slow mode at which the plastome typically evolves is likely to be influenced by a combination of different molecular mechanisms. These include the organization of plastid genes in operons, the usually uniparental mode of plastid inheritance, the activity of highly effective repair mechanisms as well as the rarity of plastid fusion. Nevertheless, structurally rearranged plastomes can be found in several unrelated lineages (e.g. ferns, Pinaceae, multiple angiosperm families). Rearrangements and gene losses seem to correlate with an unusual mode of plastid transmission, abundance of repeats, or a heterotrophic lifestyle (parasites or myco-heterotrophs). While only a few functional gene gains and more frequent gene losses have been inferred for land plants, the plastid Ndh complex is one example of multiple independent gene losses and will be discussed in detail. Patterns of ndh-gene loss and functional analyses indicate that these losses are usually found in plant groups with a certain degree of heterotrophy, might rendering plastid encoded Ndh1 subunits dispensable