Intravenous Penicillin for Antenatal Syphilotherapy

A 21 year old woman (G2 P0101) of 24 weeks gestation presented with syphilis of unknown duration. Sonography revealed fetal hydrops and placental thickening. Weekly intramuscular injections of 2.4 million U Bicillin for 3 weeks was initiated as recommended by the Centers for Disease Control. Repeat sonogram 1 week after starting treatment revealed increased ascites and a new pericardial effusion. Due to the worsening fetal condition, therapy was altered and the patient was admitted for IV penicillin. She received a continuous infusion of 18 million U penicillin G daily for 10 days. Serial sonograms showed improvement offetal ascites and pericardial effusion with 10 days of IV therapy, and complete resolution of hydrops was noted within 3 weeks. The fetus was born at term with no stigmata of congenital syphilis on newborn exam, and laboratory tests suggested adequate treatment in utero

Coupling of D2R Short but not D2R Long receptor isoform to the Rho/ROCK signaling pathway renders striatal neurons vulnerable to mutant huntingtin.

Huntington's disease, an inherited neurodegenerative disorder, results from abnormal polyglutamine extension in the N-terminal region of the huntingtin protein. This mutation causes preferential degeneration of striatal projection neurons. We previously demonstrated, in vitro, that dopaminergic D2 receptor stimulation acted in synergy with expanded huntingtin to increase aggregates formation and striatal death through activation of the Rho/ROCK signaling pathway. In vivo, in a lentiviral-mediated model of expanded huntingtin expression in the rat striatum, we found that the D2 antagonist haloperidol protects striatal neurons against expanded huntingtin-mediated toxicity. Two variant transcripts are generated by alternative splicing of the of D2 receptor gene, the D2R-Long and the D2R-Short, which are thought to play different functional roles. We show herein that overexpression of D2R-Short, but not D2R-Long in cell lines is associated with activation of the RhoA/ROCK signaling pathway. In striatal neurons in culture, the selective D2 agonist Quinpirole triggers phosphorylation of cofilin, a downstream effector of ROCK, which is abrogated by siRNAs that knockdown both D2R-Long and D2R-Short, but not by siRNAs targeting D2R-Long alone. Aggregate formation and neuronal death induced by expanded huntingtin, were potentiated by Quinpirole. This D2 agonist-mediated effect was selectively inhibited by the siRNA targeting both D2R-Long and D2R-Short but not D2R-Long alone. Our data provide evidence for a specific coupling of D2R-Short to the RhoA/ROCK/cofilin pathway, and its involvement in striatal vulnerability to expanded huntingtin. A new route for targeting Rho-ROCK signaling in Huntington's disease is unraveled with our findings

On the Impact of Re-Evaluation in 5G NR V2X Mode 2

5G NR V2X has been designed to support advanced connected and automated driving V2X services. These services are characterized by variable traffic patterns that can generate packet collisions in decentralized systems where vehicles autonomously select their radio resources like 5G NR V2X mode 2. 5G NR V2X introduces a re-evaluation mechanism at the MAC layer to detect and avoid possible packet collisions before a vehicle transmits in selected resources. Most of the studies conducted to date on 5G NR V2X do not consider the re-evaluation mechanism despite being a mandatory MAC feature. This article advances the state of the art with an in-depth analysis and evaluation of the operation and performance of re-evaluation in 5G NR V2X mode 2 under different traffic patterns and mode 2 configurations. The study shows that re-evaluation is effective in avoiding collisions with periodic traffic but its effectiveness decreases with aperiodic traffic and of variable size. The study also shows that re-evaluation is effective in avoiding collisions generated by the retransmission of packets. However, its overall impact on the performance of 5G NR V2X mode 2 is small, while it can have a relevant implementation cost due to the frequent re-evaluation checks and resource reselections. This raises questions on the current design of the re-evaluation mechanism that is a mandatory feature in 5G NR V2X mode 2

Umbilical uptakes and transplacental concentration ratios of amino acids in severe fetal growth restriction

Background: This study examines the relationship between placental amino acid (AA) transport and fetal AA demand in an ovine fetal growth restriction (FGR) model in which placental underdevelopment induces fetal hypoxemia and hypoglycemia. Methods: Umbilical uptakes of AA, oxygen, glucose, and lactate were measured near term in eight experimental ewes (FGR group) and in eight controls (C group). Results: The FGR group demonstrated significantly reduced umbilical uptakes of oxygen, glucose, lactate, and 11 AAs per kg fetus. The combined uptake of glucose, lactate, and AAs, expressed as nutrient/oxygen quotients, was reduced almost to 1.00 (FGR: 1.05 vs. C: 1.32, P ≤ 0.02). In contrast to a decrease in umbilical glucose concentration, all but one of the AAs that were transported from placenta to fetus demonstrated normal or elevated fetal concentrations, and five of the essential AAs were transported against a significantly higher feto/maternal (F/M) concentration ratio. This ratio peaked at the lowest fetal oxygen levels. Conclusion: We conclude that, in the hypoxic FGR fetus, the reduction in AA uptake is not due to a disproportionally small placental AA transport capacity. It is the consequence of decreased fetal oxidative metabolism and growth rate, which together reduce fetal AA demand. © 2013 International Pediatric Research Foundation, Inc

A Novel Technique for Mitigating Multipactor by Means of Magnetic Surface Roughness

Multipactor phenomena which are closely linked to the SEY (secondary electron yield)can be mitigated by many different methods including groves in the metal surface as well as using electric or magnetic bias fields. However frequently the application of global magnetic or electric bias field is not practicable considering the weight and power limitations on-board satellites. Additionally, surface grooves may degrade the RF performance. Here we present a novel technique which is based on a magnetostatic field pattern on the metallic surface with fast spatial modulation in the order of 30 micron. This field pattern is produced by proper magnetization of an underlying ferromagnetic layer such as nickel. Simulations and preliminary experimental results will be shown and a number of applications, both for particle accelerators and satellite microwave payloads are discussed

Direct evidence of lack of colocalisation of fluorescently labelled gold labels used in correlative light electron microscopy

Fluorescently labelled nanoparticles are routinely used in Correlative Light Electron Microscopy (CLEM) to combine the capabilities of two separate microscope platforms: fluorescent light microscopy (LM) and electron microscopy (EM). The inherent assumption is that the fluorescent label observed under LM colocalises well with the electron dense nanoparticle observed in EM. Herein we show, by combining single molecule fluorescent imaging with optical detection of the scattering from single gold nanoparticles, that for a commercially produced sample of 10 nm gold nanoparticles tagged to Alexa-633 there is in fact no colocalisation between the fluorescent signatures of Alexa-633 and the scattering associated with the gold nanoparticle. This shows that the attached gold nanoparticle quenches the fluorescent signal by ~95%, or less likely that the complex has dissociated. In either scenario, the observed fluorescent signal in fact arises from a large population of untagged fluorophores; rendering these labels potentially ineffective and misleading to the field

Applying Mendelian randomization to appraise causality in relationships between smoking, depression and inflammation

Smoking, inflammation and depression commonly co-occur and may be mechanistically linked. However, key questions remain around the direction of association and the influence of residual confounding. We aimed to characterize the association between lifetime smoking and depression, as well as to assess the role that genetically-predicted C-reactive protein (CRP) level, (an archetypal generalized inflammatory marker) and/or IL-6 activity, as a potential explanation for this association. We performed inverse variance weighted Mendelian randomization (MR) analyses using recently published summary-level GWAS data for lifetime smoking index, CRP levels, and depression. A subset of inflammatory-related genetic variants from the lifetime smoking GWAS were also used to assess the potential inflammatory causal pathways between smoking and depression. The analysis indicated reciprocal relationships of lifetime smoking with depression (ORSmk–Dep = 2.01, 95% CI 1.71–2.37, p &lt; 0.001; ORDep–Smk = 1.09, 95% CI 1.06–1.13, p &lt; 0.001), CRP levels and IL-6 activity (ORSmk–CRP = 1.40, 95% CI 1.21–1.55, p &lt; 0.001; ORCRP–Smk = 1.03, 95% CI 1.02–1.05, p &lt; 0.001, ORIL-6/CRP–Smk = 1.06 (1.03–1.09), p &lt; 0.001). These associations were also supported by the majority of the robust MR methods performed. We did not find evidence for a reciprocal relationship between CRP levels (using &gt; 500 genetic instruments for CRP) and depression (ORCRP–Dep = 1.01, 95% CI 0.99–1.04; ORDep–CRP = 1.03, 95% CI 0.99–1.07). We observed little variation in the IVW estimates between smoking and depression when we limited the genetic variants assessed to those related to measures of generalized inflammation, but we found evidence for an attenuation of the smoking-depression association in multivariable mendelian randomization when adjusting for IL-6 activity, suggesting that the IL-6 pathway may be at least in part responsible for the association of smoking and depression. Our study supports potential bidirectional causal associations between lifetime smoking and depression which may be at least in part explained by the IL-6 signalling pathway. The IL-6 pathway may represent a putative therapeutic target for smoking and to mitigate the effects of smoking on depression.</p