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Introduction: The GAIA (Global Alignment on Immunisation Safety Assessment in Pregnancy) consortium was established in 2014 with the aim of creating a standardised, globally coordinated approach to monitoring the safety of vaccines administered in pregnancy. The consortium developed twenty-six standardised definitions for classifying obstetric and infant adverse events. This systematic review sought to evaluate the current state of adverse event reporting in maternal vaccine trials following the publication of the case definitions by GAIA, and the extent to which these case definitions have been adopted in maternal vaccine safety research. Methods: A comprehensive search of published literature was undertaken to identify maternal vaccine research studies. PubMed, EMBASE, Web of Science, and Cochrane were searched using a combination of MeSH terms and keyword searches to identify observational or interventional studies that examined vaccine safety in pregnant women with a comparator group. A two-reviewer screening process was undertaken, and a narrative synthesis of the results presented. Results: 14,737 titles were identified from database searches, 435 titles were selected as potentially relevant, 256 were excluded, the remaining 116 papers were included. Influenza vaccine was the most studied (25.0%), followed by TDaP (20.7%) and SARS-CoV-2 (12.9%).Ninety-one studies (78.4%) were conducted in high-income settings. Forty-eight (41.4%) utilised electronic health-records. The majority focused on reporting adverse events of special interest (AESI) in pregnancy (65.0%) alone or in addition to reactogenicity (27.6%). The most frequently reported AESI were preterm birth, small for gestational age and hypertensive disorders. Fewer than 10 studies reported use of GAIA definitions. Gestational age assessment was poorly described; of 39 studies reporting stillbirths 30.8% provided no description of the gestational age threshold. Conclusions: Low-income settings remain under-represented in comparative maternal vaccine safety research. There has been poor uptake of GAIA case definitions. A lack of harmonisation and standardisation persists limiting comparability of the generated safety data.

Abstract Despite encouraging preclinical data, therapies to reduce ARDS mortality remains a globally unmet need, including during the COVID-19 pandemic. We previously identified extracellular nicotinamide phosphoribosyltransferase (eNAMPT) as a novel damage-associated molecular pattern protein (DAMP) via TLR4 ligation which regulates inflammatory cascade activation. eNAMPT is tightly linked to human ARDS by biomarker and genotyping studies in ARDS subjects. We now hypothesize that an eNAMPT-neutralizing mAb will significantly reduce the severity of ARDS lung inflammatory lung injury in diverse preclinical rat and porcine models. Sprague Dawley rats received eNAMPT mAb intravenously following exposure to intratracheal lipopolysaccharide (LPS) or to a traumatic blast (125 kPa) but prior to initiation of ventilator-induced lung injury (VILI) (4 h). Yucatan minipigs received intravenous eNAMPT mAb 2 h after initiation of septic shock and VILI (12 h). Each rat/porcine ARDS/VILI model was strongly associated with evidence of severe inflammatory lung injury with NFkB pathway activation and marked dysregulation of the Akt/mTORC2 signaling pathway. eNAMPT neutralization dramatically reduced inflammatory indices and the severity of lung injury in each rat/porcine ARDS/VILI model (~ 50% reduction) including reduction in serum lactate, and plasma levels of eNAMPT, IL-6, TNFα and Ang-2. The eNAMPT mAb further rectified NFkB pathway activation and preserved the Akt/mTORC2 signaling pathway. These results strongly support targeting the eNAMPT/TLR4 inflammatory pathway as a potential ARDS strategy to reduce inflammatory lung injury and ARDS mortality.

Abstract Global knockout of the nonmuscle isoform of myosin light‐chain kinase (nmMLCK), a primary cellular regulator of cytoskeletal machinery, is strongly protective in preclinical murine models of inflammatory lung injury. The current study was designed to assess the specific contribution of endothelial cell (EC) nmMLCK to the severity of murine inflammatory lung injury produced by lipopolysaccharide (LPS) and mechanical ventilation ventilator‐induced lung injury or ventilation (VILI). Responses to combined LPS/VILI exposure were assessed in: (i) wild‐type (WT) C57BL/6J mice; (ii) transgenic mice with global deletion of nmMLCK (nmMylk−/−); (iii) transgenic nmMylk−/− mice with overexpression of nmMLCK restricted to the endothelium (nmMylk−/−/ec‐tg+). Lung inflammation indices included lung histology, bronchoalveolar lavage (BAL) polymorphonuclear leukocytes (PMNs), lung protein biochemistry, tissue albumin levels, Evans blue dye (EBD) lung extravasation, and plasma cytokines (interleukin‐6 [IL‐6], keratinocyte chemoattractant [KC]/IL‐8, IL‐1bβ, extracellular nicotinamide phosphoribosyltransferase, tumor necrosis factor‐α). Compared to WT C57BL/6J mice, the severity of LPS/VILI‐induced lung injury was markedly reduced in mice with global nmMLCK deletion reflected by reductions in histologic inflammatory lung injury, BAL PMN counts, mitogen‐activated protein kinase, and NF‐kB pathway activation in lung homogenates, plasma cytokine levels, and parameters of lung permeability (increased BAL protein, tissue albumin levels, EBD lung extravasation). In contrast, mice with restricted overexpression of nmMLCK in EC (nmMylk−/−/ec‐tg+) showed significant persistence of LPS/VILI‐induced lung injury severity compared to WT mice. In conclusion, these studies strongly endorse the role of EC nmMLCK in driving the severity of preclinical inflammatory lung injury. Precise targeting of EC nmMLCK may represent an attractive therapeutic strategy to reduce lung inflammation and both lung and systemic vascular permeability.

Global comparison of The outcome of surgical techniques for spondylodiscitis Jessica Burton@, Thamer Hamdan*, Bisola Ajayi#, Mohsen Raza$, Angelo Fragkakis&, Cristina Lupu^, Timothy Bishop%, Jason Bernard! & Darren Lui**. @MB,ChB student. *Professor of Orthopaedic Surgery at Basrah University, Visiting Professor at London Imperial College and Research Fellow as Saint George’s Hospital London. #Orthopaedic and Spine Physician Associate. $Orthopaedic Registrar. &Spine Fellow. ^ Spine CNS. %Orthopaedic Spinal Surgeon. !Orthopaedic Spinal Surgeon. **Orthopaedic Spinal Surgeon. Department of Trauma and Orthopaedics, Saint George’s University Hospital, London, UK. Abstract Spondylodiscitis is an infection of the intervertebral disc and neighbouring bone. It is treated conservatively or surgically using a range of techniques. The aim of this review is to determine whether the surgical techniques between different countries have an effect on clinical outcome: postoperative complications, relapse rate, treatment failure rate or mortality rate. Many articles were screened using Ovid and Pubmed databases for studies pertaining to the surgical treatment of spondylodiscitis. Paediatric studies, tubercular/brucellar/fungal/ postoperative infection and case reports were excluded from this review. The results shows that no differences in the outcome of surgery between countries was found, and reasons for this along with solutions for moving forward with comparing surgical techniques worldwide are noted. Key words: Spondylodiscitis, Surgery, Outcome, Comparison, Literature review

Researchers have usually focused on the Tintin and Astérix series’ global book diffusion through translation. However, little has been discussed about the distribution policies of the comics magazine format, a key factor in the development of European comics. This paper will consider the continentalization of western European national comics industries via the intra-EEC networking of distribution channels during the 1960s. By facilitating the exchange of comics features in the Franco-Belgian area, publishers such as Casterman, Le Lombard, and Dargaud ensured the rise of the industry and of the products they wanted to disseminate. Contemplating the motivations of publishers this article will delve deeper into the emergence of cooperative and competitive distribution channels among national publishers and between countries. Through the archives of Casterman and primary sources this article intends to contribute to a greater understanding of how the carefully planned distribution network of comics influenced the development of the European industry as a whole.