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The multidrug-resistant bacteria Acinetobacter baumannii is a major cause of hospital-associated infection; a vaccine could significantly reduce this burden. The aim was to develop a clinically relevant model of A. baumannii respiratory tract infection and to test the impact of different immunization routes on protective immunity provided by an outer membrane vesicle (OMV) vaccine. BALB/c mice were intranasally challenged with isolates of oxa23 -positive global clone GC2 A. baumannii from the lungs of patients with ventilator-associated pneumonia. Mice were immunized with OMVs by the intramuscular, subcutaneous or intranasal routes; protection was determined by measuring local and systemic bacterial load. Infection with A. baumannii clinical isolates led to a more disseminated infection than the prototype A. baumannii strain ATCC17978; with bacteria detectable in upper and lower airways and the spleen. Intramuscular immunization induced an antibody response but did not protect against bacterial infection. However, intranasal immunization significantly reduced airway colonization and prevented systemic bacterial dissemination. Use of clinically relevant isolates of A. baumannii provides stringent model for vaccine development. Intranasal immunization with OMVs was an effective route for providing protection, demonstrating that local immunity is important in preventing A. baumannii infection. [Display omitted] • Clinical A. baumannii isolates cause more severe respiratory infection in mice. • Outer membrane vesicles induce strong antibody responses and reduce bacterial load. • Intramuscular and subcutaneous OMV vaccination induce systemic IgG and IgM response. • Intranasal immunization with OMVs induce systemic IgG, IgM, and mucosal IgA response. • Intranasal vaccination with OMVs protects against respiratory tract infection. [ABSTRACT FROM AUTHOR]

Orthognathic camouflage refers to the use of procedures other than traditional orthognathic surgery for correction of facial dysmorphology that reflects underlying skeletal discrepancy that was either not addressed on initial orthodontic evaluation or not corrected by nonsurgical treatment of the malocclusion. The authors aim to illustrate to the orthodontic community the common clinical presentation of patients who seek consultation from a surgeon citing dissatisfaction with their facial appearance secondary to orthodontic correction of the malocclusion with dental compensation but without surgical correction of the underlying skeletal discrepancy. This article summarizes the orthognathic camouflage procedures that are available as options for correction of such deformities without subjecting the patient to the potential morbidity and prolonged recovery associated with orthognathic surgery. This manuscript represents Part II of a two-part series describing a surgeon's approach to patients who present with facial skeletal disharmony after orthodontic treatment with dental compensation for malocclusions associated with an underlying skeletal discrepancy. [ABSTRACT FROM AUTHOR]

It is not uncommon for orthodontists to encounter patients whose malocclusion results, at least in part, from an underlying skeletal discrepancy. In many patients, these discrepancies can be fully corrected with growth modification with or without dental compensation to achieve a Class I occlusal relationship. A subset of patients with moderate skeletal deformities in whom surgery is ideally indicated but who choose to defer surgical treatment may be at risk for long-term adverse consequences on facial esthetics. As a surgeon who performs both orthognathic and facial esthetic surgery, the senior author has had the opportunity to appreciate the contributions of underlying skeletal deformities to his patients' esthetic concerns. These patients often present years after orthodontic treatment with complaints of early facial soft tissue laxity, facial disproportion, and overall dissatisfaction with facial appearance. The authors hope to illustrate to the orthodontic community the clinical picture of adult patients who present to the offices of surgeons dissatisfied with their appearance secondary to the uncorrected skeletal deformity. This paper aims to increase orthodontists' awareness of the long-term effects of uncorrected skeletal dysplasia on facial appearance. The ultimate goal is to allow the informed consent process to incorporate these esthetic consequences and to facilitate patient decision making. This article serves as Part I of a 2-part series reviewing a surgeon's approach to patients who present with facial skeletal disharmony after orthodontic treatment with dental compensation. [ABSTRACT FROM AUTHOR]

Coronary artery disease is associated with impaired clot structure. The aim of this study was to investigate acute phase myocardial infarction (AMI) and provide detailed quantitative analysis of clot ultrastructure. Clot formation and breakdown, pore size, fiber density, fiber radius and protofibril packing were investigated in plasma clots from AMI patients. These data were compared to those from healthy controls. Analysis on clot formation using turbidity showed increased lag time, suggesting changes in protofibril packing and increased fiber size for AMI patients compared to healthy controls. Additionally, increased average rate of clotting and decreased time to maximum absorbance in AMI patients suggest that clots formed more quickly. Moreover, we observed increased time from max OD to max rate of lysis. Increased fibrinogen and decreased plasminogen in AMI patients were accounted for in represented significant differences. AMI samples showed increased time to 25% and 50% lysis, but no change in 75% lysis, representative of delayed lysis onset, but expediated lysis once initiated. These data suggest that AMI patients formed less porous clots made from more densely packed fibers with decreased numbers of protofibrils, which was confirmed using decreased permeation and increased fiber density, and decreased turbidimetry. AMI plasma formed clots that were denser, less permeable, and lysed more slowly than healthy controls. These findings were confirmed by detailed analysis of clot ultrastructure, fiber size, and protofibril packing. Dense clot structures that are resistant to lysis may contribute to a prothrombotic milieu in AMI. [ABSTRACT FROM AUTHOR]

In Asia, there are an estimated 12 million annual cases of enteric fever, a potentially fatal systemic bacterial infection caused by Salmonella enterica serovars Typhi (STy) and Paratyphi A (SPA). The recent availability of typhoid conjugate vaccines (TCV), an increasing incidence of disease caused by SPA and growing antimicrobial resistance (AMR) across the genus Salmonella makes a bivalent STy/SPA vaccine a useful public health proposition. The uptake of a stand-alone paratyphoid vaccine is likely low thus, there is a pipeline of bivalent STy/SPA candidate vaccines. Several candidates are close to entering clinical trials, which if successful should facilitate a more comprehensive approach for enteric fever control. Additionally, the World Health Organization (WHO) has made advancing the development of vaccines that protect young children and working aged adults against both agents of enteric fever a priority objective. This "Vaccine Value Profile" (VVP) addresses information related predominantly to invasive disease caused by SPA prevalent in Asia. Information is included on stand-alone SPA candidate vaccines and candidate vaccines targeting SPA combined with STy. Out of scope for the first version of this VVP is a wider discussion on the development of a universal Salmonella combination candidate vaccine, addressing both enteric fever and invasive non-typhoidal Salmonella disease, for use globally. This VVP is a detailed, high-level assessment of existing, publicly available information to inform and contextualize the public health, economic, and societal potential of pipeline vaccines and vaccine-like products for SPA. Future versions of this VVP will be updated to reflect ongoing activities such as vaccine development strategies and "Full Vaccine Value Assessment" that will inform the value proposition of an SPA vaccine. This VVP was developed by an expert working group from academia, non-profit organizations, public–private partnerships, and multi-lateral organizations as well as in collaboration with stakeholders from the WHO South-East Asian Region. All contributors have extensive expertise on various elements of the VVP for SPA and collectively aimed to identify current research and knowledge gaps. [ABSTRACT FROM AUTHOR]