The role of antibiotics in the prevention of preterm birth

There are multiple uses for antibiotics during pregnancy: treatment of intercurrent bacterial infections such as urinary or respiratory tract infections, maternal treatment to prevent fetal or neonatal disease, prophylactic treatment for surgical procedures, and treatment of puerperal infections. This report will summarize the current recommendations for the use of antibiotics specifically to reduce the risk of preterm birth

The use of antenatal magnesium sulfate for neuroprotection for infants born prematurely

Cerebral palsy occurs in three to four infants per 1000 live births. Preterm birth prior to 34 weeks’ gestation is a major risk factor. Five randomized controlled trials of antenatal magnesium sulfate (MgSO4) found a trend of reduced risk of cerebral palsy and mortality in preterm infants. Three meta-analyses using the data from the five randomized controlled trials, which included a total of 5235 prospectively evaluated fetuses, found that MgSO4 given to women at risk of premature birth significantly reduced the risk of cerebral palsy by 30% without increasing the risk of perinatal or infant death. The implication for clinical practice is that MgSO4 should be considered for use in patients at high risk of delivery before 34 weeks’ gestation

Comparison of a Trial of Labor with an Elective Second Cesarean Section

BACKGROUND: In an attempt to reduce the rate of cesarean section, obstetricians now offer a trial of labor to pregnant women who have had a previous cesarean section. Although a trial of labor is usually successful and is relatively safe, few studies have directly addressed the maternal and perinatal morbidity and mortality associated with this method of delivery. METHODS: We performed a population-based, longitudinal study of 6138 women in Nova Scotia who had previously undergone cesarean section and had delivered a singleton live infant in the period from 1986 through 1992. RESULTS: A total of 3249 women elected a trial of labor, and 2889 women chose to undergo a second cesarean section. There were no maternal deaths. The overall rate of maternal morbidity was 8.1 percent; 1.3 percent had major complications (a need for hysterectomy, uterine rupture, or operative injury) and 6.9 percent had minor complications (puerperal fever, a need for blood transfusion, or abdominal-wound infection). Although the overall rate of maternal complications did not differ significantly between women who chose a trial of labor and the women who elected cesarean section (odds ratio for the trial-of-labor group, 0.9; 95 percent confidence interval, 0.8 to 1.1), major complications were nearly twice as likely among women undergoing a trial of labor (odds ratio, 1.8; 95 percent confidence interval, 1.1 to 3.0). Apgar scores, admission to the neonatal intensive care unit, and perinatal mortality were similar among the infants whose mothers had a trial of labor and those whose mothers underwent elective cesarean section. CONCLUSION: Among pregnant women who have had a cesarean section, major maternal complications are almost twice as likely among those whose deliveries are managed with a trial of labor as among those who undergo an elective second cesarean section

Cervicoisthmic cerclage: transabdominal vs transvaginal approach

To compare the outcomes of cervicoisthmic cerclage (CI) using traditional transabdominal (TA) approach versus the lesser utilized transvaginal (TV) approach

Novel role for the innate immune receptor toll-like receptor 4 (TLR4) in the regulation of the wnt signaling pathway and photoreceptor apoptosis

Recent evidence has implicated innate immunity in regulating neuronal survival in the brain during stroke and other neurodegenerations. Photoreceptors are specialized light-detecting neurons in the retina that are essential for vision. In this study, we investigated the role of the innate immunity receptor TLR4 in photoreceptors. TLR4 activation by lipopolysaccharide (LPS) significantly reduced the survival of cultured mouse photoreceptors exposed to oxidative stress. With respect to mechanism, TLR4 suppressed Wnt signaling, decreased phosphorylation and activation of the Wnt receptor LRP6, and blocked the protective effect of the Wnt3a ligand. Paradoxically, TLR4 activation prior to oxidative injury protected photoreceptors, in a phenomenon known as preconditioning. Expression of TNFα and its receptors TNFR1 and TNFR2 decreased during preconditioning, and preconditioning was mimicked by TNFα antagonists, but was independent of Wnt signaling. Therefore, TLR4 is a novel regulator of photoreceptor survival that acts through the Wnt and TNFα pathways. © 2012 Yi et al

Are current dynamic water quality models too complex? A comparison of a new parsimonious phosphorus model, SimplyP, and INCA-P

Catchment-scale water quality models are becoming increasingly popular tools for exploring the potential effects of land management, land use change and climate change on water quality. However, the dynamic, catchment-scale nutrient models in common usage are complex, with many uncertain parameters requiring calibration, limiting their usability and robustness. A key question is whether this complexity is justified. To explore this, we have developed a parsimonious P model, SimplyP, incorporating a coupled rainfall-runoff model and a biogeochemical model able to simulate streamflow, suspended sediment, particulate and dissolved P dynamics. The model’s complexity is compared in a small rural catchment in northeast Scotland. For three land use classes, less than six SimplyP model parameters must be determined through calibration alone, the rest may be based on measurements; INCA-P has around 40 unmeasurable parameters. Despite simpler process-representation, SimplyP produced a slightly better dissolved P simulation during both calibration and validation, and produced similar long-term projections in response to changes in land management. Results support the hypothesis that INCA-P is overly complex for the study catchment. We hope our findings will help prompt wider model comparison exercises, as well as debate amongst the water quality modelling community as to whether today's models are fit for purpose. Simpler models such as SimplyP have the potential to be useful management and research tools, building blocks for future model development (prototype code is freely available), or benchmarks against which more complex models could be evaluated

Study protocol: Determinants of participation and quality of life of adolescents with cerebral palsy: a longitudinal study (SPARCLE2)

<p>Abstract</p> <p>Background</p> <p>Children and adults with impairments such as cerebral palsy have lower participation in life situations than able-bodied people. Less is known about their subjective perception of their lives, called their quality of life.</p> <p>During adolescence, rapid physical and psychological changes occur; although these may be more difficult for disabled than for able-bodied adolescents, little research has examined the lives of disabled adolescents.</p> <p>In 2003-4 a European Union funded project, SPARCLE, visited 818 children aged 8-12 years with cerebral palsy, sampled from population-based registers in nine European regions. The quality of life reported by these disabled children was similar to that of the general population but their participation was lower; levels of participation varied between countries even for children with similar severity of cerebral palsy.</p> <p>We are currently following up these children, now aged 13-17 years, to identify (i) to what extent contemporaneous factors (pain, impairment, psychological health and parental stress) predict their participation and quality of life, (ii) what factors modify how participation and quality of life at age 8-12 years are associated with participation and quality of life in adolescence, and (iii) whether differences between European countries in participation and quality of life can be explained by variations in environmental factors.</p> <p>Methods/Design</p> <p>Trained researchers will visit families to administer questionnaires to capture the adolescents' type and severity of impairment, socio-demographic characteristics, participation, quality of life, psychological health, pain, environmental access and parental stress. We will use multivariable models (linear, logistic or ordinal) to assess how adolescent participation, quality of life, psychological health, pain, environmental access and parental stress, vary with impairment and socio-demographic characteristics and, where possible, how these outcomes compare with general population data. For participation and quality of life, longitudinal analyses will assess to what extent these are predicted by corresponding levels in childhood and what factors modify this relationship. Structural equation modelling will be used to identify indirect relationships mediated by other factors.</p

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease