Intravenous immunoglobulin for the treatment of severe maternal alloimmunization: individual patient data meta-analysis.

OBJECTIVE: This study aimed to investigate the outcomes associated with the administration of maternal intravenous immunoglobulin in high-risk red blood cell-alloimmunized pregnancies. DATA SOURCES: Medline, Embase, and Cochrane Library were systematically searched until June 2023. STUDY ELIGIBILITY CRITERIA: This review included studies reporting on pregnancies with severe red blood cell alloimmunization, defined as either a previous fetal or neonatal death or the need for intrauterine transfusion before 24 weeks of gestation in the previous pregnancy as a result of hemolytic disease of the fetus and newborn. METHODS: Cases were pregnancies that received intravenous immunoglobulin, whereas controls did not. Individual patient data meta-analysis was performed using the Bayesian framework. RESULTS: Individual patient data analysis included 8 studies consisting of 97 cases and 97 controls. Intravenous immunoglobulin was associated with prolonged delta gestational age at the first intrauterine transfusion (gestational age of current pregnancy - gestational age at previous pregnancy) (mean difference, 3.19 weeks; 95% credible interval, 1.28-5.05), prolonged gestational age at the first intrauterine transfusion (mean difference, 1.32 weeks; 95% credible interval, 0.08-2.50), reduced risk of fetal hydrops at the time of first intrauterine transfusion (incidence rate ratio, 0.19; 95% credible interval, 0.07-0.45), reduced risk of fetal demise (incidence rate ratio, 0.23; 95% credible interval, 0.10-0.47), higher chances of live birth at ≥28 weeks (incidence rate ratio, 1.88; 95% credible interval, 1.31-2.69;), higher chances of live birth at ≥32 weeks (incidence rate ratio, 1.93; 95% credible interval, 1.32-2.83), and higher chances of survival at birth (incidence rate ratio, 1.82; 95% credible interval, 1.30-2.61). There was no substantial difference in the number of intrauterine transfusions, hemoglobin level at birth, bilirubin level at birth, or survival at hospital discharge for live births. CONCLUSION: Intravenous immunoglobulin treatment in pregnancies at risk of severe early hemolytic disease of the fetus and newborn seems to have a clinically relevant beneficial effect on the course and severity of the disease.

Kinesin-4 optimizes microtubule orientations for responsive tip growth guidance in moss.

Tip-growing cells of, amongst others, plants and fungi secrete wall materials in a highly polarized fashion for fast and efficient colonization of the environment. A polarized microtubule cytoskeleton, in which most microtubule ends are directed toward the growing apex, has been implicated in directing growth. Its organizing principles, in particular regarding maintenance of network unipolarity, have remained elusive. We show that a kinesin-4 protein, hitherto best known for a role in cytokinesis, suppresses encounters between antiparallel microtubules. Without this activity, microtubules hyper-aligned along the growth axis and increasingly grew away from the apex. Cells themselves displayed an overly straight growth path and a delayed gravitropic response. This result revealed conflicting systemic needs for a stable growth direction and an ability to change course in response to extracellular cues. Thus, the use of selective inhibition of microtubule growth at antiparallel overlaps constitutes a new organizing principle within a unipolar microtubule array.

Exchange transfusions in severe Rh-mediated alloimmune haemolytic disease of the foetus and newborn: a 20-year overview on the incidence, associated risks and outcome.

BACKGROUND AND OBJECTIVES: Guidelines and indications for exchange transfusion in haemolytic disease of the foetus and newborn (HDFN) have changed drastically in the past decades, causing a decline in exchange transfusion rate. This study aims to evaluate the incidence of exchange transfusions (ETs) in neonates with Rh-mediated HDFN over the past 20 years at our centre, and report potentially ET-related complications as well as indicators for bilirubin encephalopathy. MATERIAL AND METHODS: In this observational study, 438 neonates were included with HDFN, born ≥ 35 weeks gestational age at the Leiden University Medical Centre between January 2000 and July 2020. The incidence of ET and procedure-related complications were assessed in three consecutive time periods determined by changes in guidelines and indications for ET. RESULTS: The incidence of ET in our centre declined from (104/156) 67% (time period 2000-2005), to (39/181) 22% (2006-2015) and to (10/101) 10% (2015-2020, p < 0·001). The maximum bilirubin levels in neonates after birth increased from 13·6 mg/dL (or 233 µmol/L), to 15·0 mg/dL (257 µmol/L) and to 15·3 mg/dL (263 µmol/L). The incidence of complications associated with the use of ET (including sepsis, haematologic disorders and respiratory failure) remained stable throughout the years, and no neonates died during the study period. CONCLUSION: Exchange transfusion incidence declined significantly over the past two decades. Decrease in ET incidence, and concomitant decrease in exposure and expertise, was not associated with an increase in procedure-related complications.

Plasticity in colloidal gel strands.

Colloidal gels are space-spanning networks of aggregated particles. The mechanical response of colloidal gels is governed, to a large extent, by the properties of the individual gel strands. To study how colloidal gels respond to repeated deformations, we perform Brownian dynamics simulations on single strands of aggregated colloidal particles. While current models assume that gel failure is due to the brittle rupture of gel strands, our simulations show that gel strands undergo large plastic deformations prior to breaking. Rearrangement of particles within the strands leads to plastic lengthening and softening of the strands, which may ultimately lead to strand necking and ductile failure. This failure mechanism occurs irrespective of the thickness and length of the strands and the range and strength of the interaction potential. Rupture of gel strands is more likely for long and thin strands and for a long-ranged interaction potential.

Strand Plasticity Governs Fatigue in Colloidal Gels.

The repeated loading of a solid leads to microstructural damage that ultimately results in catastrophic material failure. While posing a major threat to the stability of virtually all materials, the microscopic origins of fatigue, especially for soft solids, remain elusive. Here we explore fatigue in colloidal gels as prototypical inhomogeneous soft solids by combining experiments and computer simulations. Our results reveal how mechanical loading leads to irreversible strand stretching, which builds slack into the network that softens the solid at small strains and causes strain hardening at larger deformations. We thus find that microscopic plasticity governs fatigue at much larger scales. This gives rise to a new picture of fatigue in soft thermal solids and calls for new theoretical descriptions of soft gel mechanics in which local plasticity is taken into account.

Depletion-Induced Encapsulation by Dumbbell-Shaped Patchy Colloids Stabilize Microspheres against Aggregation.

In this paper, we demonstrate the stabilization of polystyrene microspheres by encapsulating them with dumbbell-shaped colloids with a sticky and a nonsticky lobe. Upon adding a depletant, an effective short ranged attraction is induced between the microspheres and the smaller, smooth lobes of the dumbbells, making those specifically sticky, whereas the interaction with the larger lobes of the dumbbells is considerably less attractive due to their rough surface, which reduces the overlap volume and leaves them nonsticky. The encapsulation of the microspheres by these rough-smooth patchy dumbbells is investigated using a combination of experiments and computer simulations, both resulting in partial coverage of the template particles. For larger microspheres, the depletion attraction is stronger, resulting in a larger fraction of dumbbells that are attached with both lobes to the surface of microspheres. We thus find a template curvature dependent orientation of the dumbbells. In the Monte Carlo simulations, the introduction of such a small, curvature dependent attraction between the rough lobes of the dumbbells resulted in an increased coverage. However, kinetic constraints imposed by the dumbbell geometry seem to prevent optimal packing of the dumbbells on the template particles under all investigated conditions in experiments and simulations. Despite the incomplete coverage, the encapsulation by dumbbell particles does prevent aggregation of the microspheres, thus acting as a colloid-sized steric stabilizer.