Characterization of lab-based swarms of Anopheles gambiae mosquitoes using 3D-video tracking.

Mosquito copulation is a crucial determinant of its capacity to transmit malaria-causing Plasmodium parasites as well as underpinning several highly-anticipated vector control methodologies such as gene drive and sterile insect technique. For the anopheline mosquitoes responsible for African malaria transmission, mating takes place within crepuscular male swarms which females enter solely to mate. However, the mechanisms that regulate swarm structure or that govern mate choice remain opaque. We used 3D-video tracking approaches and computer vision algorithms developed for the study of other complex biological systems to document swarming behavior of a lab-adapted Anopheles gambiae line in a lab-based setting. By reconstructing trajectories of individual mosquitoes lasting up to 15.88 s, in swarms containing upwards of 200 participants, we documented swarm-like behavior in both males and females. In single sex swarms, encounters between individuals were fleeting (< 0.75 s). By contrast, in mixed swarms, we were able to detect 79 'brief encounters' (> 0.75 s; < 2.5 s) and 17 longer-lived encounters (> 2.5 s). We also documented several examples of apparent male-male mating competition. These findings represent the first steps towards a more detailed and quantitative description of swarming and courtship behavior in one of the most important vectors of malaria.

Collective response to local perturbations: how to evade threats without losing coherence.

Living groups move in complex environments and are constantly subject to external stimuli, predatory attacks and disturbances. An efficient response to such perturbations is vital to maintain the group's coherence and cohesion. Perturbations are often local, i.e. they are initially perceived only by few individuals in the group, but can elicit a global response. This is the case of starling flocks, that can turn very quickly to evade predators. In this paper, we investigate the conditions under which a global change of direction can occur upon local perturbations. Using minimal models of self-propelled particles, we show that a collective directional response occurs on timescales that grow with the system size and it is, therefore, a finite-size effect. The larger the group is, the longer it will take to turn. We also show that global coherent turns can only take place if i) the mechanism for information propagation is efficient enough to transmit the local reaction undamped through the whole group; and if ii) motility is not too strong, to avoid that the perturbed individual leaves the group before the turn is complete. No compliance with such conditions results in the group's fragmentation or in a non-efficient response.

Microbiota-Associated HAF-EVs Regulate Monocytes by Triggering or Inhibiting Inflammasome Activation.

In pregnancy, human amniotic fluid extracellular vesicles (HAF-EVs) exert anti-inflammatory effects on T cells and on monocytes, supporting their immunoregulatory roles. The specific mechanisms are still not completely defined. The aim of this study was to investigate the ability of HAF-EVs, isolated from pregnant women who underwent amniocentesis and purified by gradient ultracentrifugation, to affect inflammasome activation in the human monocytes. Proteomic studies revealed that HAF-EV samples expressed several immunoregulatory molecules as well as small amounts of endotoxin. Surprisingly, metagenomic analysis shows the presence of specific bacterial strain variants associated with HAF-EVs as potential sources of the endotoxin. Remarkably, we showed that a single treatment of THP-1 cells with HAF-EVs triggered inflammasome activation, whereas the same treatment followed by LPS and ATP sensitization prevented inflammasome activation, a pathway resembling monocyte refractories. A bioinformatics analysis of microbiota-HAF-EVs functional pathways confirmed the presence of enzymes for endotoxin biosynthesis as well as others associated with immunoregulatory functions. Overall, these data suggest that HAF-EVs could serve as a source of the isolation of a specific microbiota during early pregnancy. Moreover, HAF-EVs could act as a novel system to balance immune training and tolerance by modulating the inflammasome in monocytes or other cells.

Signatures of irreversibility in microscopic models of flocking.

Flocking in d=2 is a genuine nonequilibrium phenomenon for which irreversibility is an essential ingredient. We study a class of minimal flocking models whose only source of irreversibility is self-propulsion and use the entropy production rate (EPR) to quantify the departure from equilibrium across their phase diagrams. The EPR is maximal in the vicinity of the order-disorder transition, where reshuffling of the interaction network is fast. We show that signatures of irreversibility come in the form of asymmetries in the steady-state distribution of the flock's microstates. These asymmetries occur as consequences of the time-reversal symmetry breaking in the considered self-propelled systems, independently of the interaction details. In the case of metric pairwise forces, they reduce to local asymmetries in the distribution of pairs of particles. This study suggests a possible use of pair asymmetries both to quantify the departure from equilibrium and to learn relevant information about aligning interaction potentials from data.

Renormalization group approach to connect discrete- and continuous-time descriptions of Gaussian processes.

Discretization of continuous stochastic processes is needed to numerically simulate them or to infer models from experimental time series. However, depending on the nature of the process, the same discretization scheme may perform very differently for the two tasks, if it is not accurate enough. Exact discretizations, which work equally well at any scale, are characterized by the property of invariance under coarse-graining. Motivated by this observation, we build an explicit renormalization group (RG) approach for Gaussian time series generated by autoregressive models. We show that the RG fixed points correspond to discretizations of linear SDEs, and only come in the form of first order Markov processes or non-Markovian ones. This fact provides an alternative explanation of why standard delay-vector embedding procedures fail in reconstructing partially observed noise-driven systems. We also suggest a possible effective Markovian discretization for the inference of partially observed underdamped equilibrium processes based on the exploitation of the Einstein relation.

Marginal speed confinement resolves the conflict between correlation and control in collective behaviour.

Speed fluctuations of individual birds in natural flocks are moderate, due to the aerodynamic and biomechanical constraints of flight. Yet the spatial correlations of such fluctuations are scale-free, namely they have a range as wide as the entire group, a property linked to the capacity of the system to collectively respond to external perturbations. Scale-free correlations and moderate fluctuations set conflicting constraints on the mechanism controlling the speed of each agent, as the factors boosting correlation amplify fluctuations, and vice versa. Here, using a statistical field theory approach, we suggest that a marginal speed confinement that ignores small deviations from the natural reference value while ferociously suppressing larger speed fluctuations, is able to reconcile scale-free correlations with biologically acceptable group's speed. We validate our theoretical predictions by comparing them with field experimental data on starling flocks with group sizes spanning an unprecedented interval of over two orders of magnitude.

Effectiveness and safety of available treatments for COVID-19 during pregnancy: a critical review.

BACKGROUND: COVID-19 is a pandemic disease caused by the SARS-CoV-2 and it spread globally in the last few months. The complete lack of specific treatment forced clinicians to use old drugs, chosen for their efficacy against similar viruses or their in vitro activity. Trials on patients are ongoing but the majority of information comes from small case series and single center reports. We aimed to provide a literature review on the putative effectiveness and safety of available treatments for COVID-19 in pregnant women. METHODS: We reviewed all the available literature concerning the drugs that have been used in the treatment of COVID-19 during pregnancy and whose safe assumption during pregnancy had been demonstrated by clinical studies (i.e. including studies on other infectious diseases). Drugs contra-indicated during pregnancy or with unknown adverse effects were not included in our review. RESULTS AND CONCLUSIONS: Clinical trials are not often conducted among pregnant patients for safety reasons and this means that drugs that may be effective in general population cannot be used for pregnant women due to the lack of knowledge of side effects in this category of people .The choice to use a specific drug for COVID-19 in pregnancy should take into account benefits and possible adverse events in each single case. In the current situation of uncertainty and poor knowledge about the management of COVID-19 during pregnancy, this present overview may provide useful information for physicians with practical implications.

First trimester HtrA1 maternal plasma level and spontaneous preterm birth.

OBJECTIVES: High temperature requirement A1 (HtrA1) is a serine protease detected in maternal plasma and in placental tissues during normal gestation and in various pathological conditions. The purpose of this study was to determine whether the maternal plasma concentration of HtrA1 in first trimester, alone or combined with other maternal factors, can be used to identify women at risk for spontaneous preterm birth (SPTB). STUDY DESIGN: This is a cohort study on pregnant women at 12 weeks of gestation recruited between 2014 and 2016 and prospectively followed until delivery. One hundred and fifty-nine women were included in the study: 140 women delivered at term and 19 (11.9%) delivered spontaneously preterm. Plasma samples were assessed for HtrA1 by ELISA and data were compared between women which delivered at term with women which delivered preterm. A multiple logistic regression analysis was used to estimate the independent effect of women's characteristics on the probability of a SPTB. RESULTS: SPTB was significantly associated with log HtrA1 values at 12 weeks of gestation, BMI before pregnancy and physical activity. In particular, the probability of a SPTB increases of 79% for every added unit of log HtrA1, while decreases of 18% for every added unit of BMI. In addition, physical activity was found as an important protective factor. The ROC curve showed that the model had a good accuracy in predicting SPTB, with an AUC equal to 0.83 (95%CI: 0.73-0.91). CONCLUSIONS: Maternal plasma HtrA1 may be considered a marker of SPTB. In addition, our model indicates two factors that could be modified to reduce the risk of SPTB, i.e. BMI before pregnancy and maternal physical activity.

Brain 3D-echographic early predictors of neuro-behavioral disorders in infants: a prospective observational study.

BACKGROUND: Prematurity, low birth weight (LBW), very low birth weight (VLBW), and intrauterine growth restriction (IUGR) are risk factors of long-term poor neuro-development outcomes and associate with reduction of regional brain volumes. OBJECTIVE: To evaluate the possible role of 3D ultrasound sonography (3DUS) regional brain volumes, measured at 30-40 days of postnatal period, as early predictors of long-term risk of neuro-behavioral disorders. METHODS: A highly selected population, which included: full-term, preterm, IUGR, and preterm-IUGR born individuals, was followed longitudinally from 30 to 40 days of postnatal period to the second year of life. The population was mostly composed of bichorionic twins to ensure a, theoretically, major intracategory homogeneity. Preterm and IUGR subjects were characterized by a gestational age (GA) and birth weight (BW)>32 weeks and >1500 g, respectively, whereas the full-term neonates were of 37 weeks GA. At enrollment, the assessment of the volumetric measurements was performed using the 3DUS. The evaluation of neuro-development was performed at 2 years using the Griffiths Mental Development Scales. RESULTS: The 3DUS measurements of whole brain, thalamus, frontal cortex, and cerebellum volumes, assessed at 30-40 days of postnatal period, were significantly reduced in infants characterized by negative outcome. In addition, the respective areas of the ROC curves, made by comparing values of normal and abnormal neuro-development groups, were indicative of a strong diagnostic accuracy. CONCLUSION: Data found suggest that the 3DUS regional brain volumes may assume a significant role as early indicators of neonates at major risk of neuro-behavioral disorders in later life. Further and larger studies in this direction are needed to validate this significant perspective.

Endometrial receptivity and pregnancy outcome.

Human implantation is a highly complex and multifactorial process. Successful implantation requires the presence of a healthy embryo, a receptive endometrium, and a synchronized molecular dialogue between the two, as well as immune tolerance/protection from the host. The endometrial receptivity refers to a hormonally limited period in which the endometrial tissue acquires a transient functional status allowing blastocyst implantation and pregnancy initiation. Global knowledge of endometrial receptivity grew up in recent years. Improvements in genetics, new biomarkers, noninvasive methods, new advanced techniques (Endometrial receptivity assay - the ERA system, proteomic analysis) offer the possibility to evaluate the endometrial status and to manage patients with infertility problems, especially women undergoing assisted reproductive treatment. This overview reports the most relevant knowledge and recent advances in the study of implantation processes from the perspective of the endometrium, often considered as being the main barrier for a successful pregnancy initiation. Endometrial receptivity is a topic of great interest and further studies are needed for the early identification of endometrial abnormalities and the discovery of new strategies for increasing the chance for the establishment of pregnancy.

Dynamical Renormalization Group for Mode-Coupling Field Theories with Solenoidal Constraint.

The recent inflow of empirical data about the collective behaviour of strongly correlated biological systems has brought field theory and the renormalization group into the biophysical arena. Experiments on bird flocks and insect swarms show that social forces act on the particles' velocity through the generator of its rotations, namely the spin, indicating that mode-coupling field theories are necessary to reproduce the correct dynamical behaviour. Unfortunately, a theory for three coupled fields-density, velocity and spin-has a prohibitive degree of intricacy. A simplifying path consists in getting rid of density fluctuations by studying incompressible systems. This requires imposing a solenoidal constraint on the primary field, an unsolved problem even for equilibrium mode-coupling theories. Here, we perform an equilibrium dynamic renormalization group analysis of a mode-coupling field theory subject to a solenoidal constraint; using the classification of Halperin and Hohenberg, we can dub this case as a solenoidal Model G. We demonstrate that the constraint produces a new vertex that mixes static and dynamical coupling constants, and that this vertex is essential to grant the closure of the renormalization group structure and the consistency of dynamics with statics. Interestingly, although the solenoidal constraint leads to a modification of the static universality class, we find that it does not change the dynamical universality class, a result that seems to represent an exception to the general rule that dynamical universality classes are narrower than static ones. Our results constitute a solid stepping stone in the admittedly large chasm towards developing an off-equilibrium mode-coupling theory of biological groups.

Obstetric and psychosocial risk factors associated with maternity blues.

AIM: To identify risk factors for maternity blues (MB) and to evaluate the impact of obstetric factors on MB prevalence. MATERIALS AND METHODS: 194 mothers have completed the Edinburgh Postnatal Depression Scale (EPDS) 2 days after delivery. Bivariate and multivariate logistic regression models were used to identify the predictors of MB. RESULTS: 57 women (29.4%) were positive at screening. Comparing the two groups, no statistically significant difference was found in age (p = .536), nationality (p = .065) and BMI before pregnancy (p = .224). Interestingly, no significant differences were highlighted in terms of assisted reproduction technology or spontaneous pregnancies and the presence of labor analgesia, while MB was significantly more frequent in case of cesarean section (CS) (p = .035). Statistical differences have been found in previous CS (p = .022), previous voluntary interruption of pregnancy (p = .021), number of previous pregnancies (p = .007), Apgar 5' (p = .026), lower level of education (p = .009), and previous postpartum depression (PPD) (p = .026). A logistic regression analysis was realized according to a multivariate model incorporating all the variables with a p-value ≤.25 in bivariate analysis. In the final model vaginal delivery (OR 0.451, 95% CI [0.224-0.911], p = .026) resulted to be MB protective factor, while a lower level of education (OR 3.657, 95% CI [1.482-9.023], p = .005) as well as previous PPD (OR 4.714, 95% CI [1.273-17.458], p = .020) were identified as independent risk factors. CONCLUSION: This study showed that a lower education level and a previous PPD resulted to be important risk factors for MB development, while natural delivery was revealed as a protective factor. These results could be used to develop a better and more accurate prevention program after delivery.

The effect of prenatal exposure to music on fetal movements and fetal heart rate: a pilot study.

OBJECTIVE: To assess and compare fetal cardiac parameters of fetuses listening to music before and during nonstress test, only during the test or never. STUDY DESIGN: Thirty healthy mother-fetus dyads were randomized in a 1:1:1 ratio to one of three groups: group A in which fetuses were submitted to prelistening phase (33rd + 0 to 36th + 3 week) and listening sessions during 4 nonstress tests, group B in which fetuses were submitted to listening sessions during 4 nonstress tests, and group C receiving 4 nonstress tests without any listening. We assessed mean fetal heart rate, fetal heart rate accelerations, fetal heart rate decelerations, fetal movements and uterine contractility. RESULTS: Fetuses of the group A, who had already listened to a particular piece of music during previous sessions, had significantly increased their heart rate accelerations and movements during the music listening session of the last nonstress test. No significant changes were observed in the number of uterine contractions. CONCLUSIONS: Our findings show that fetuses slightly respond to that music they know, but they do not significantly respond to unknown music.

Maternal tetanus, diphtheria, and acellular pertussis (Tdap) and influenza immunization: an overview.

BACKGROUND: Maternal tetanus, diphtheria, and acellular pertussis (Tdap) and influenza immunization for women during pregnancy (the so-called "maternal immunization") has been introduced in several countries, and recently also in Italy, to protect mother and fetus during pregnancy, infant in his first months of life and mother during postpartum period. However, very low vaccination coverage rates have been reached due to several variables. METHODS: A literature search was conducted on PubMed and Embase, including any experimental or observational studies, to assesses existing evidence on the effectiveness, efficacy, safety and optimal timing of administration of Tdap and influenza immunization in pregnancy for mothers and their infants. The search was finalized in August 2019. RESULTS: Reviewing the literature, we identified only a few studies that, among several maternal and infant outcomes, found sporadic significant associations with maternal influenza immunization and even less with Tdap immunization. Moreover, most of the authors of these studies explained these findings as a result of residual confounding effect. The effectiveness of maternal influenza immunization is more complicated to prove than the effectiveness of Tdap immunization because of several reasons. Not all nations recommend and offer vaccines in the same weeks of pregnancy and this one manifests the complexity in defining the best timing for Tdap or influenza immunization. CONCLUSIONS: The safety of maternal Tdap or influenza immunization is supported by the evidence so far, however, regular surveillance should be maintained, especially with regard to the influenza vaccine that changes in formulation each year. There is a need to optimize the timing of vaccination in pregnancy and to have a national system of detection of maternal immunization in each country.

Pre-eclampsia predictive ability of maternal miR-125b: a clinical and experimental study.

Pre-eclampsia (PE) is a systemic maternal syndrome affecting 2-8% of pregnancies worldwide and involving poor placental perfusion and impaired blood supply to the foetus. It manifests after the 20th week of pregnancy as new-onset hypertension and substantial proteinuria and is responsible for severe maternal and newborn morbidity and mortality. Identifying biomarkers that predict PE onset prior to its establishment would critically help treatment and attenuate outcome severity. MicroRNAs are ubiquitous gene expression modulators found in blood and tissues. Trophoblast cell surface antigen (Trop)-2 promotes cell growth and is involved in several cancers. We assessed the PE predictive ability of maternal miR-125b in the first trimester of pregnancy by measuring its plasma levels in women with normal pregnancies and with pregnancies complicated by PE on the 12th week of gestation. To gain insight into PE pathogenesis we investigated whether Trop-2 is targeted by miR-125b in placental tissue. Data analysis demonstrated a significant association between plasma miR-125b levels and PE, which together with maternal body mass index before pregnancy provided a predictive model with an area under the curve of 0.85 (95% confidence interval, 0.70-1.00). We also found that Trop-2 is a target of miR-125b in placental cells; its localization in the basal part of the syncytiotrophoblast plasma membrane suggests a role for it in the early onset of PE. Altogether, maternal miR-125b proved a promising early biomarker of PE, suggesting that it may be involved in placental development through its action on Trop-2 well before the clinical manifestations of PE.

Dynamical Renormalization Group Approach to the Collective Behavior of Swarms.

We study the critical behavior of a model with nondissipative couplings aimed at describing the collective behavior of natural swarms, using the dynamical renormalization group under a fixed-network approximation. At one loop, we find a crossover between an unstable fixed point, characterized by a dynamical critical exponent z=d/2, and a stable fixed point with z=2, a result we confirm through numerical simulations. The crossover is regulated by a length scale given by the ratio between the transport coefficient and the effective friction, so that in finite-size biological systems with low dissipation, dynamics is ruled by the unstable fixed point. In three dimensions this mechanism gives z=3/2, a value significantly closer to the experimental window, 1.0≤z≤1.3, than the value z≈2 numerically found in fully dissipative models, either at or off equilibrium. This result indicates that nondissipative dynamical couplings are necessary to develop a theory of natural swarms fully consistent with experiments.

Renormalization group crossover in the critical dynamics of field theories with mode coupling terms.

Motivated by the collective behavior of biological swarms, we study the critical dynamics of field theories with coupling between order parameter and conjugate momentum in the presence of dissipation. Under a fixed-network approximation, we perform a dynamical renormalization group calculation at one loop in the near-critical disordered region, and we show that the violation of momentum conservation generates a crossover between an unstable fixed point, characterized by a dynamic critical exponent z=d/2, and a stable fixed point with z=2. Interestingly, the two fixed points have different upper critical dimensions. The interplay between these two fixed points gives rise to a crossover in the critical dynamics of the system, characterized by a crossover exponent κ=4/d. The crossover is regulated by a conservation length scale R_{0}, given by the ratio between the transport coefficient and the effective friction, which is larger as the dissipation is smaller: Beyond R_{0}, the stable fixed point dominates, while at shorter distances dynamics is ruled by the unstable fixed point and critical exponent, a behavior which is all the more relevant in finite-size systems with weak dissipation. We run numerical simulations in three dimensions and find a crossover between the exponents z=3/2 and z=2 in the critical slowdown of the system, confirming the renormalization group results. From the biophysical point of view, our calculation indicates that in finite-size biological groups mode coupling terms in the equation of motion can significantly change the dynamical critical exponents even in the presence of dissipation, a step toward reconciling theory with experiments in natural swarms. Moreover, our result provides the scale within which fully conservative Bose-Einstein condensation is a good approximation in systems with weak symmetry-breaking terms violating number conservation, as quantum magnets or photon gases.

Induction of the apoptotic pathway by oxidative stress in spontaneous preterm birth: Single nucleotide polymorphisms, maternal lifestyle factors and health status.

The purpose of the present study was to search for associations between spontaneous preterm birth (sPTB), single nucleotide polymorphisms (SNPs) associated with the apoptotic pathway as triggered by oxidative stress, maternal lifestyle and health status. SNP genotyping [rs7560 for c-Jun N-terminal kinase (JNK), rs9517320 for mammalian STE20-like protein kinase 3 (MST3), rs1049216 for caspase 3 (CASP3)] in the placenta and maternal blood of 300 controls with at-term birth and 43 cases of sPTB was performed. No association was identified in genotype frequencies or combinations of foetal/maternal genotypes between single SNPs and sPTB. The risk of sPTB was significantly reduced by physical activity and significantly increased by current hypertensive diseases, premature rupture of membranes (PROM) or preterm PROM (P-PROM) and previous sPTB. The TT/GA genotype of JNK/CASP3 in maternal blood and maternal health status (current hypertensive diseases, current PROM/P-PROM, previous sPTB) were independently associated with sPTB. The present findings suggested that, independently of other maternal factors, pregnant women carrying the TT/GA genotype of JNK/CASP3 were more susceptible to sPTB than women bearing the GT/GA (our reference) genotype; that the apoptotic pathway triggered by oxidative stress was involved; and that genetic and non-genetic factors contributed to sPTB. Knowledge of these aspects may aid to improve the management of pregnancies by indicating the lifestyle to be adopted on the basis of sPTB susceptibility.

[New methods for preterm birth prediction: the PAMG-1 test].

BACKGROUND: The aim of this study was to assess the efficacy of PAMG-1 test (placental alpha microglobulin-1) in cervicovaginal secretions collected immediately following transvaginal ultrasound (TVUS) of women with signs and symptoms of preterm labor (PTL), clinically intact membranes and cervical length between 15 and 30 mm for the prediction of imminent spontaneous delivery (within 7 days of testing), as well as delivery <34 weeks of gestation. METHODS: Performing PAMG-1 test in 79 women with singleton pregnancy (240/7 -336/7 weeks' gestation) reporting signs and symptoms indicative of PTL and cervical length <30 mm. RESULTS: For PTB prediction risk within 7 days of testing in pregnant women with cervicale length between 15-30 mm sensitivity is 100% and specificity is 94%. Positive predictive value (PPV) is 77% and negative predictive value (NPV) is 100%. For delivery prediction <34 weeks of gestation sensitivity decreased from 100% to 67% and specificity from 94% to 89%, PPV is 55% and NPV 93%. CONCLUSIONS: The inaccuracy of traditional methods, including biophysical tests, biochemical markers, or the combination of both, for assessing the risk of spontaneous preterm birth in patients presenting with symptoms of PTL often leads to unnecessary admission and administration of corticosteroids and tocolytics. The PAMG-1 test demonstrated high efficacy in identifying women at risk of imminent PTL within 7 days of testing, despite being performed immediately after TVUS. High NPV can prevent improper admission and unnecessary therapies for mother and fetus.