Adaptive pathfinding by nucleokinesis during amoeboid migration.

Motile cells encounter microenvironments with locally heterogeneous mechanochemical composition. Individual compositional parameters, such as chemokines and extracellular matrix pore sizes, are well known to provide guidance cues for pathfinding. However, motile cells face diverse cues at the same time, raising the question of how they respond to multiple and potentially competing signals on their paths. Here, we reveal that amoeboid cells require nuclear repositioning, termed nucleokinesis, for adaptive pathfinding in heterogeneous mechanochemical micro-environments. Using mammalian immune cells and the amoeba Dictyostelium discoideum, we discover that frequent, rapid and long-distance nucleokinesis is a basic component of amoeboid pathfinding, enabling cells to reorientate quickly between locally competing cues. Amoeboid nucleokinesis comprises a two-step polarity switch and is driven by myosin-II forces that readjust the nuclear to the cellular path. Impaired nucleokinesis distorts path adaptions and causes cellular arrest in the microenvironment. Our findings establish that nucleokinesis is required for amoeboid cell navigation. Given that many immune cells, amoebae, and some cancer cells utilize an amoeboid migration strategy, these results suggest that nucleokinesis underlies cellular navigation during unicellular biology, immunity, and disease.

Lack of consensus in the choice of termination of pregnancy for Turner syndrome in France.

BACKGROUND: The observed rate of termination of pregnancy (TOP) for Turner syndrome varies worldwide and even within countries. In this vignette study we quantified agreement among ten multidisciplinary prenatal diagnosis centers in Paris. METHODS: We submitted online three cases of Turner syndrome (increased nuchal translucency, normal ultrasound, aortic coarctation) to fetal medicine experts: one obstetrician, one pediatrician and one geneticist in each of the ten Parisian centers. Each case was presented in the form of a progressive clinical history with conditional links dependent upon responses. The background to each case was provided, along with the medical history of the parents and the counseling they got from medical staff. The experts indicated online whether or not they would accept the parents' request for TOP. We assessed the percentage of agreement for acceptance or refusal of TOP. We also used a multilevel logistic regression model to evaluate differences among obstetrician-gynecologists, pediatricians and cytogeneticists. RESULTS: Overall agreement among the experts to accept or refuse TOP was, respectively, 25 and 28%. The percentage of disagreement was 47%. The percentage of agreement to accept TOP was 33, 8 and 33% for obstetrician-gynecologists, pediatricians and cytogeneticists, respectively. The respective percentages of agreement to refuse TOP were 19, 47 and 26%. CONCLUSION: Our results show the lack of consensus with regard to decisions related to termination of pregnancy for Turner Syndrome. This lack of consensus in turn underscores the importance of multidisciplinary management of these pregnancies in specialized fetal medicine centers.

The risk of prelabor and intrapartum cesarean delivery among overweight and obese women: possible preventive actions.

OBJECTIVE: The purpose of this study was to investigate prelabor and intrapartum cesarean delivery in overweight and obese women by parity, previous cesarean delivery, and labor induction to assess what preventive actions might be possible. STUDY DESIGN: We modeled relative risks (RRs) and risk differences of prelabor and intrapartum cesarean delivery by prepregnancy body mass index (obese, ≥30 kg/m(2); overweight, 25-29.9 kg/m(2); normal weight, 18.5-24.9 kg/m(2)) in a nationally representative sample of 12,297 French women. Models were stratified by parity and previous cesarean status. Covariates included maternal sociodemographic characteristics, medical conditions, pregnancy complications, and induction of labor. RESULTS: Risks of prelabor cesarean delivery were elevated only for obese multiparous women. This reflected not only a higher prevalence of previous cesarean delivery (26.4% vs 17.9% for normal-weight women) but also higher risks of prelabor cesarean delivery for multiparous women with no previous cesarean delivery after adjustment for medico-obstetric factors (RR, 1.82; 95% confidence interval [CI], 1.25-2.64). Obese primiparous women and multiparous women with no previous cesarean delivery had similarly increased adjusted RRs for intrapartum cesarean delivery (RR, 1.64; 95% CI, 1.36-1.98; and RR, 1.66; 95% CI, 1.15-2.39, respectively), but the risk difference was higher for primiparous women, with an absolute increase of 0.10 (95% CI, 0.05-0.14) compared with 0.02 (95% CI, 0.00-0.04) for multiparous women. Increased intrapartum cesarean delivery risks for primiparous women were related to more frequent labor induction (42.6% vs 23.8% for normal-weight women). CONCLUSION: It may be possible to reduce primary and thus repeat cesarean delivery rates among obese women by preventive actions targeting labor induction in primiparous women and prelabor cesarean deliveries in multiparous women. Further research is needed on the impact of limiting inductions on cesarean delivery risks for obese primiparous women.

Cerebral Doppler velocimetry to predict fetal anemia after more than three intravenous fetal exchange transfusions.

BACKGROUND: We aimed to assess usefulness of the middle cerebral artery peak systolic velocity (MCA-PSV) in the prediction of fetal anemia after more than three intravenous fetal-exchange transfusions (IFET). STUDY DESIGN AND METHODS: A retrospective study was conducted over 6 years of 15 consecutive pregnancies with severe red blood cell fetomaternal alloimmunization requiring more than three IFETs. We evaluated correlation between MCA-PSV (expressed as multiples of the mean [MoM]) and pretransfusion hemoglobin (Hb) in the fetus (MoM). Analyses were also performed to assess the value of MCA-PSV to predict moderate to severe fetal anemia. RESULTS: Twenty-seven MCA-PSV measurements performed before the fourth to last IFET were coupled with pretransfusion Hb in the fetus. The median number of IFETs per fetus was five (range, four to eight). Five Hb samples found fetuses with severe (19%), seven with moderate (26%), and 15 with mild anemia (56%). There was a linear correlation between MCA-PSV(x) and Hb in the fetus(y): y = -0.21x + 0.93 (r = -0.50, p < 0.01). For the prediction of moderate to severe anemia the negative predictive value of MCA-PSV with a threshold of 1.5 MoM was 75%, positive predictive value 73%, specificity 80%, sensibility 67%, and positive likelihood ratio 3.33. The area under the receiver operating characteristic curve was 0.78 (95% confidence interval, 0.59-0.96; p < 0.001). For the prediction of severe anemia, MCA-PSV with a threshold of 1.5 MoM had 94% negative predictive value, 80% sensibility, and a positive likelihood ratio of 2.5. CONCLUSIONS: This study shows that a correlation between MCA-PSV and Hb in the fetus persists even after more than three IFETs. MCA-PSV measurements thus remain useful to monitor fetuses at risk of anemia.

Nuchal translucency measurement: are qualitative and quantitative quality control processes related?

OBJECTIVES: Two types of quality assurance processes for nuchal translucency (NT) measurement have been described: qualitative through review of images and quantitative comparison of operator's specific NT distribution to reference distributions. The aim of this study was to assess the results of these two approaches. METHODS: Prospective evaluation of sonologists affiliated to the French Ultrasound College who first underwent qualitative evaluation based on the College Français d'Echographie Foetale (CFEF) score. During one year, those same sonologists measured the NT for Down syndrome screening purposes. The operator's specific NT distributions were compared to their CFEF score, their number of unsatisfactory images and their number of NT measurements per year. RESULTS: The study involved 1726 sonologists who performed 174 722 first-trimester examinations. Mean (SD) quantitative score was 23.4/32 (+/-7.4). The median [inter-quantile range] number of examinations per sonologist was 69 [37; 123]. The median [range] NT multiples of the mean (MoM) value was 0.81 [0.46; 1.22]. NT (MoM) absolute deviation from 1 MoM was significantly correlated with mean score obtained (R(2) = -0.17, p < 0.0001), number of unacceptable images (R(2) = 0.14, p < 0.0001) and number of ultrasound scans performed per year (R(2) = -0.19, p < 0.0001). CONCLUSION: Our results suggest that both processes are clearly related.

Maternal characteristics associated with gestational weight gain in France: a population-based, nationally representative study.

OBJECTIVES: To provide nationally representative estimates of gestational weight gain (GWG) and identify maternal characteristics associated with inadequate GWG in France. DESIGN: A population-based study using data from the French National Perinatal Survey: 2010 and 2016. SETTING: All maternity units in metropolitan, mainland France (n=535 in 2010; n=493 in 2016). PARTICIPANTS: Singleton live births with GWG data (N=24 850). PRIMARY OUTCOME MEASURES: GWG was calculated as end of pregnancy minus pre-pregnancy weight (kg) and categorised as 'insufficient', 'adequate', or 'excessive' using 2009 Institute of Medicine thresholds. Classification accounted for pre-pregnancy body mass index (BMI) (kg/m2; underweight (<18.5), normal weight (18.5-24.9), overweight (25-29.9), obese (≥30)) and gestational age at birth. We estimated average GWG and the percentage of women in each GWG category. Polytomous logistic regression identified characteristics associated with GWG adequacy. RESULTS: Average GWG was 13.0 kg (SD 5.6), with 26.8% of women gaining insufficiently, 37.0% adequately and 36.1% excessively. Among other factors, insufficient GWG was associated with underweight (vs normal weight; adjusted OR (aOR) 1.4, 95% CI 1.2 to 1.5) and obese (aOR 1.5, 95% CI 1.4 to 1.7) BMI. Excessive GWG was associated with overweight (aOR 2.8, 95% CI 2.6 to 3.1) and obese BMI (aOR 3.3, 95% CI 2.9 to 3.6). Examining obesity classes separately, odds of insufficient GWG increased from obesity class I to III, while odds of excessive GWG decreased from obesity class I to III. Primiparity (insufficient: aOR 0.9, 95% CI 0.9 to 1.0; excessive: aOR 1.2, 95% CI 1.2 to 1.3), maternal characteristics indicative of lower socioeconomic status, and continuing or quitting smoking during pregnancy were also associated with inadequate GWG. CONCLUSIONS: In France, insufficient and excessive GWG are common. For optimal outcomes, clinician education, with special attention to the needs of higher risk/vulnerable groups, is needed to ensure all women receive appropriate advice for recommended GWG.

Out-of-hospital diagnosis of a ruptured ectopic pregnancy: myometrial embryo implantation, an exceptional diagnosis.

BACKGROUND: Ultrasonography (US) could be used in emergency out-of-hospital settings to diagnose abdominal hemorrhage. OBJECTIVES: To report the diagnosis by US of a suspected case of ruptured ectopic pregnancy despite a supposedly in utero pregnancy. CASE REPORT: A mobile intensive care unit with an emergency physician on board was sent out to a 22-year-old woman suffering from acute abdominal pain. On the previous day, an 11-week pregnancy had been diagnosed and the pelvic US images were reported to be "normal." Physical examination revealed that the patient was in shock. Point-of-care US detected an intraperitoneal effusion and suspected uterine rupture. Emergency laparotomy revealed an 11- or 12-week intra-abdominal pregnancy with uterine rupture due to myometrial implantation of the embryo. CONCLUSION: Ultrasound is a helpful tool in emergency care, particularly in out-of-hospital settings. An earlier "normal" US examination cannot definitively exclude uterine rupture.

Consequences of delayed measles vaccination in Germany.

BACKGROUND: In recent surveillance data there are still many cases of measles and even local epidemics in Germany. We studied whether delayed measles vaccination contributes to this situation. METHODS: Vaccine coverage data in children <3 years of age were assessed by a telephone survey. Three data sources for measles surveillance were analyzed: official measles notifications; sentinel data; and official hospital discharge diagnoses. RESULTS: After the time recommended for completion of measles vaccination at Month 15, only 22% of German children had received their first vaccine dose. This percentage increased to 77% at the age of 24 months and to 87% at 36 months of age. According to all three surveillance instruments, the number of measles cases was highest in children age 1 to 4 years with a peak in the second year of life. CONCLUSIONS: More than 50% of measles cases in 1-year-old children would be prevented if presently observed vaccine coverage rates in the third year of life could be achieved 12 months earlier. Delayed measles vaccination is responsible for a large number of measles cases still occurring in the German population, where measles has not yet been eliminated. If vaccination were delivered according to the recommended time schedule, the incidence of measles would be considerably reduced.

Prediction of the potential benefit of different pneumococcal conjugate vaccines on invasive pneumococcal disease in German children.

BACKGROUND: In the US a pneumococcal conjugate vaccination program with a 7-valent conjugate vaccine was successfully implemented in 2000. How much invasive pneumococcal disease can potentially be prevented by the 7-valent (or 11-valent) vaccine in Europe? METHODS: Prospective, active surveillance of invasive pneumococcal disease in German children age <16 years was performed between 1997 and 2000. Age- and disease-specific coverage and incidence rates were assessed in children old enough to benefit from complete vaccination to estimate the annual number of cases potentially preventable. RESULTS: A total of 1,743 cases were reported; 667 isolates were serotyped. Coverage of 7-valent (11-valent) conjugate vaccines in children age 6 months and older was age- and diagnosis-dependent, ranging from 10.5% (15.8%) to 78.3% (82.6%) for meningitis and from 13.6% (68.2%) to 75.0% (89.3%) for nonmeningitis invasive pneumococcal disease cases. Of an estimated annual number of 176 children with pneumococcal meningitis age 6 months or older, 112 (122) cases had serotypes included in the 7-valent (11-valent) conjugate vaccine compared with 181 (254) of 324 nonmeningitis invasive pneumococcal disease cases, with 37 of the 73 cases covered by the 11-valent vaccine only in children older than 5 years. Regarding meningitis in this age group the potential benefit was equally poor for both the 7-valent (12 of 37 cases) and the 11-valent vaccine (15 of 37 cases). CONCLUSION: Coverage of the 7- and 11-valent conjugate vaccines depends markedly on age and disease. The additional potential benefit of the 11-valent compared with the 7-valent vaccine for pneumococcal meningitis was marginal.

Childhood obesity is associated with maternal smoking in pregnancy.

UNLABELLED: Overweight and obesity are major public health issues. Childhood obesity often persists throughout adulthood. Recently a higher prevalence of obesity in adults whose mothers smoked during pregnancy was reported. The aim of this study was to assess whether this association is also detectable in pre-school children in a different setting and to identify the critical period for intrauterine exposure to inhaled smoke products in pregnancy. We analysed questionnaire data on early feeding and lifestyle factors of 8,765 German children aged 5.00 to 6.99 years. Obesity was defined as a body mass index >97th percentile. The prevalence estimates for obesity were: mother never smoked 2.8% (95% CI 2.4%-3.2%), smoked after pregnancy only 1.6% (95%CI 0.4%-4.1%), smoked throughout pregnancy 6.2% (95% CI 4.5%-8.3%), smoked before pregnancy, but not throughout 4.5% (95%CI 3.6%-5.7%). These associations could not be explained by confounding due to a number of constitutional, sociodemographic and lifestyle factors. The unadjusted/adjusted odds ratios were: smoked during pregnancy: 2.32 (95% CI 1.63%-3.30%)/1.92 (95% CI 1.29%-2.86%); smoked before, but not throughout pregnancy: 1.67 (95%CI 1.26%-2.22%)/1.74 (95%CI 1.29%-2.34%). CONCLUSION: the association of maternal smoking in pregnancy and obesity was also detectable in children at school entry. Since smoking after pregnancy was not associated with childhood obesity, intrauterine exposure rather than family lifestyle factors associated with smoking appears to be instrumental. There appears to be a role for early intrauterine exposure.

Will the 7-valent pneumococcal vaccine have a similar impact on all invasive pneumococcal infections in children in Germany as in the Kaiser Permanente Trial?

UNLABELLED: A 7-valent pneumococcal conjugate (7-vPc) vaccine was shown to be highly effective in California preventing 89.1% of all invasive pneumococcal infections (IPI) regardless of serotype. There is concern whether a similar effectiveness will be attained in Germany where 52% of all IPI in children <16 years were caused by the serotypes in the vaccine. The study was based on prospective, active surveillance of IPI in German children aged <16 years during 1997 to 2000. Coverage by the 7-vPc vaccine (with and without 6A) in unvaccinated children in the Kaiser Permanente Trial (KPT) was compared to the coverage in German children in the same age period as in the KPT. The proportion of potentially preventable cases was estimated both for unvaccinated children in the KPT and for Germany by multiplication of the coverage rates with the vaccine efficacy estimate from the KPT (intention to treat analysis). Successful serotyping could be attained for 38.3% of the 1,743 German IPI cases. In the age period from 7 to 43 months concerned in the KPT, the proportion of cases with serotypes covered by the 7-vPc vaccine (+6A) was 91% (95% CI 80%-97%) in the unvaccinated children in the KPT compared to 76% (95% CI 71%-80%) in Germany. The respective estimates for the number of potentially preventable IPI cases were 85% (95% CI 75%-91%) in the KPT compared to 71% (95% CI 67%-75%) in Germany. CONCLUSION: Age specific serotype coverage rates have to be considered for extrapolation of the Kaiser Permanente Trial to the German situation. Although 14% lower than in the Kaiser Permanente Trial, 71% of potentially preventable cases of invasive pneumococcal infection still predict an excellent effectiveness for the 7-valent pneumococcal conjugate vaccine in Germany.