Pregnant women and measles: we need to be vigilant during outbreaks.

A number of countries including the UK are currently experiencing large outbreaks of measles affecting mainly young children but also adolescents and young adults. Women of childbearing age are a particular group of concern because the 1988 Wakefield Lancet paper, which falsely asserted a connection between the MMR vaccine and autism, was associated with a large and sharp decline in childhood MMR uptake over several years. This has left large cohorts of non-immune adolescents and young adults (born between 1998 and 2004), including young women who are now of childbearing age and remain susceptible to measles as well as rubella. Pregnant mothers are at higher risk of serious complications, such as pneumonia, with adverse pregnancy complications including fetal loss, premature birth, and neonatal death. Measles infection may also result in subacute sclerosing panencephalitis (SSPE), a very rare but very severe and invariably fatal neurodegenerative complication that typically manifests many years after acute measles infection but can have a short-onset latency with a fulminant course in pregnant women. Here, we summarise the epidemiology of measles infection, factors associated with the current measles outbreaks, as well as the risks and outcomes of measles, including SSPE, in pregnancy. We propose an algorithm for clinical management of measles infection in pregnancy. We also highlight the importance of early liaison with local health protection teams for risk assessment, diagnosis and management of suspected measles in pregnancy and close contacts as well as susceptible pregnant women exposed to a person with measles in the community

Recent increase in infant pertussis cases in Europe and the critical importance of antenatal immunisations: we must do better…now.

Recent months have seen an increase in pertussis cases in several countries across the Northern and Southern hemispheres. The lack of immune stimulation during the COVID-19 pandemic due to the reduced circulation of Bordetella pertussis, the pathogen responsible for pertussis, is likely to have led to increased population susceptibility which has been magnified the typical 3-5 yearly cyclical peaks in activity. Maternal immunization for pertussis proves highly effective in protecting infants under three months of age. It's also critical for immunisers and parents to maintain high and timely immunisation uptake to ensure infants receive maximum early protection when they are most at risk of severe disease

Urea Cycle Related Amino Acids Measured in Dried Bloodspots Enable Long-Term In Vivo Monitoring and Therapeutic Adjustment

BACKGROUND: Dried bloodspots are easy to collect and to transport to assess various metabolites, such as amino acids. Dried bloodspots are routinely used for diagnosis and monitoring of some inherited metabolic diseases. METHODS: Measurement of amino acids from dried blood spots by liquid chromatography-tandem mass spectrometry. RESULTS: We describe a novel rapid method to measure underivatised urea cycle related amino acids. Application of this method enabled accurate monitoring of these amino acids to assess the efficacy of therapies in argininosuccinate lyase deficient mice and monitoring of these metabolites in patients with urea cycle defects. CONCLUSION: Measuring urea cycle related amino acids in urea cycle defects from dried blood spots is a reliable tool in animal research and will be of benefit in the clinic, facilitating optimisation of protein-restricted diet and preventing amino acid deprivation

A Search for leptophilic Z_(l) boson at future linear colliders

We study the possible dynamics associated with leptonic charge in future linear colliders. Leptophilic massive vector boson, Z_(l), have been investigated through the process e^(+)e^(-) -> mu^(+)mu^(-). We have shown that ILC and CLIC will give opportunity to observe Z_(l) with masses up to the center of mass energy if the corresponding coupling constant g_(l) exceeds 10^(-3).Comment: 12 pages, 10 figure

EM703 improves bleomycin-induced pulmonary fibrosis in mice by the inhibition of TGF-β signaling in lung fibroblasts

BACKGROUND: Fourteen-membered ring macrolides have been effective in reducing chronic airway inflammation and also preventing lung injury and fibrosis in bleomycin-challenged mice via anti-inflammatory effects. EM703 is a new derivative of erythromycin (EM) without the bactericidal effects. We investigated the anti-inflammatory and antifibrotic effects of EM703 in an experimental model of bleomycin-induced lung injury and subsequent fibrosis in mice. METHODS: Seven-week-old male ICR mice were used. All experiments used eight mice/group, unless otherwise noted in the figure legends. Bleomycin was administered intravenously to the mice on day 0. EM703 was orally administered daily to mice. All groups were examined for cell populations in the bronchoalveolar lavage (BAL) fluid and for induction of messenger RNA (mRNA) of Smad3 and Smad4 in the lung tissues by reverse transcriptase (RT)-polymerase chainreaction (PCR) on day 7. Fibroblastic foci were assessed histologically, and the hydroxyproline content was chemically determined in the lung tissues on day 28. We performed assay of proliferation and soluble collagen production, and examined the induction of mRNA of Smad3 and Smad4 by RT-PCR in murine lung fibroblast cell line MLg2908. We also examined Smad3, Smad4 and phosphorylated Smad2/3 (p-Smad2/3) protein assay by western blotting in MLg2908. RESULTS: Bleomycin-induced lung fibrosis, and the infiltration of macrophages and neutrophils into the airspace were inhibited by EM703. The expression of Smad3 and Smad4 mRNA was clearly attenuated by bleomycin, but was recovered by EM703. EM703 also inhibited fibroblast proliferation and the collagen production in lung fibroblasts induced by Transforming growth factor-beta (TGF-β). The expression of Smad3 and Smad4 mRNA in murine lung fibroblasts disappeared due to TGF-β, but was recovered by EM703. EM703 inhibited the expression of p-Smad2/3 and Smad4 protein in murine lung fibroblasts induced by TGF-β. CONCLUSION: These findings suggest that EM703 improves bleomycin-induced pulmonary fibrosis in mice by actions of anti-inflammation and regulation of TGF-β signaling in lung fibroblasts

Evaluation of immunogenicity and reactogenicity of COVID-19 vaccines in pregnant women.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is associated with increased risk of adverse maternal and perinatal outcomes. Vaccines are highly effective at preventing severe coronavirus disease 2019 (COVID-19), but there are limited data on COVID-19 vaccines in pregnancy. This study aimed to investigate the reactogenicity and immunogenicity of COVID-19 vaccines in pregnant women when administered according to the 12-week-interval dosing schedule recommended in the UK. METHODS: This was a cohort study of pregnant women receiving COVID-19 vaccination between April and September 2021. The outcomes were immunogenicity and reactogenicity after COVID-19 vaccination. Pregnant women were recruited by phone, e-mail and/or text and were vaccinated according to vaccine availability at their local vaccination center. For immunogenicity assessment, blood samples were taken at specific timepoints after each dose to evaluate nucleocapsid protein (N) and spike protein (S) antibody titers. The comparator group comprised non-pregnant female healthcare workers in the same age group who were vaccinated as part of the national immunization program in a contemporaneous longitudinal cohort study. Longitudinal changes in serum antibody titers and association with pregnancy status were assessed using a two-step regression approach. Reactogenicity assessment in pregnant women was undertaken using an online questionnaire. The comparator group comprised non-pregnant women aged 18-49 years who had received two vaccine doses in primary care. The association of pregnancy status with reactogenicity was assessed using logistic regression analysis. RESULTS: Overall, 67 pregnant women, of whom 66 had received a mRNA vaccine, and 79 non-pregnant women, of whom 50 had received a mRNA vaccine, were included in the immunogenicity study. Most (61.2%) pregnant women received their first vaccine dose in the third trimester, while 3.0% received it in the first trimester and 35.8% in the second trimester. SARS-CoV-2 S-antibody geometric mean concentrations after mRNA vaccination were not significantly different at 2-6 weeks after the first dose but were significantly lower at 2-6 weeks after the second dose in infection-naïve pregnant compared with non-pregnant women. In pregnant women, prior infection was associated with higher antibody levels at 2-6 weeks after the second vaccine dose. Reactogenicity analysis included 108 pregnant women and 116 non-pregnant women. After the first dose, tiredness and chills were reported less commonly in pregnant compared with non-pregnant women (P = 0.043 and P = 0.029, respectively). After the second dose, feeling generally unwell was reported less commonly (P = 0.046) in pregnant compared with non-pregnant women. CONCLUSIONS: Using an extended 12-week interval between vaccine doses, antibody responses after two doses of mRNA COVID-19 vaccine were found to be lower in pregnant compared with non-pregnant women. Strong antibody responses were achieved after one dose in previously infected women, regardless of pregnancy status. Pregnant women reported fewer adverse events after both the first and second dose of vaccine. These findings should now be addressed in larger controlled studies. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology