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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]

Antimicrobial resistance (AMR) represents a major challenge to global health. This problem is most apparent in healthcare facilities, with a comparatively small number of pathogens being responsible for a substantial burden of hospital acquired infections globally. One of the key pathogens is the Gram-negative coccobacilli, Acinetobacter baumannii. It has been estimated that between 47% and 93% of A. baumannii infections are associated with multi-drug resistance (MDR), which is facilitated through a variety of well documented mechanisms (β-lactamases, efflux pumps, aminoglycoside-modifying enzymes, permeability defects, and target modifications). As our current pool of antimicrobial treatments becomes increasingly less effective, it is vital to identify new targets that can aid in the development novel treatments and strategies. In this we review we outline the key virulence mechanisms in A. baumannii (gene acquisition and adaptation, resistance to stresses, biofilm formation, and host interaction) and discuss their potential as targets for new therapeutics to reduce the impact of infections caused by MDR A. baumannii. [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]

Objectives: We assessed the impact of MALDITOF-MS on the timeliness of optimal antimicrobial therapy through a parallel-arm randomised controlled trial in two hospitals in Vietnam.Methods: We recruited patients with a pathogen (bacterial or fungal) cultured from a normally sterile sample. Samples were randomly assigned (1:1) to identification by MALDITOF-MS or conventional diagnostics. The primary outcome was the proportion on optimal antimicrobial therapy within 24 h of positive culture, determined by a blinded independent review committee. Trial registered at ClinicalTrials.gov (NCT02306330).Results: Among 1005 randomised patients, pathogens were isolated from 628 (326 intervention, 302 control), with 377 excluded as likely contaminants or discharged/died before positive culture. Most isolates were cultured from blood (421/628, 67.0%). The proportion receiving optimal antimicrobial therapy within 24 h (the primary outcome) or 48 h of growth was not significantly different between MALDITOF-MS and control arms (135/326, 41.4% vs 120/302, 39.7%; Adjusted Odds ration (AOR) 1.17, p = 0.40 and 151/326, 46.3% vs 141/302, 46.7%; AOR 1.05 p = 0.79, respectively).Conclusions: MALDITOF-MS, in the absence of an antimicrobial stewardship programme, did not improve the proportion on optimal antimicrobial therapy at 24 or 48 h after first growth in a lower-middle income setting with high rates of antibiotic resistance. [ABSTRACT FROM AUTHOR]

Typhoid fever is an acute systemic infectious disease responsible for an estimated 12-20 million illnesses and over 150 000 deaths annually. In March, 2018, a new recommendation was issued by WHO for the programmatic use of typhoid conjugate vaccines in endemic countries. Health economic analyses of typhoid vaccines have informed funding decisions and national policies regarding vaccine rollout. However, by focusing only on averted typhoid cases and their associated costs, traditional cost-effectiveness analyses might underestimate crucial benefits of typhoid vaccination programmes, because the potential effect of typhoid vaccines on the treatment of patients with non-specific acute febrile illnesses is not considered. For every true case of typhoid fever, three to 25 patients without typhoid disease are treated with antimicrobials unnecessarily, conservatively amounting to more than 50 million prescriptions per year. Antimicrobials for suspected typhoid might therefore be an important selective pressure for the emergence and spread of antimicrobial resistance globally. We propose that large-scale, more aggressive typhoid vaccination programmes-including catch-up campaigns in children up to 15 years of age, and vaccination in lower incidence settings-have the potential to reduce the overuse of antimicrobials and thereby reduce antimicrobial resistance in many bacterial pathogens. Funding bodies and national governments must therefore consider the potential for broad reductions in antimicrobial use and resistance in decisions related to the rollout of typhoid conjugate vaccines. [ABSTRACT FROM AUTHOR]

The objective was to determine if consistent pain management during vaccine injections has a beneficial effect on future infant pain reactivity. This was a multicenter, longitudinal, double-blind, double-dummy, add-on, randomized controlled trial. Healthy infants were randomized to 1 of 4 add-on pain management regimens for all vaccinations in the first year of life: 1) placebo control (standard care), 2) parent video education about infant soothing (video), 3) video and oral sucrose solution (sucrose), 4) video and sucrose and topical liposomal lidocaine (lidocaine). At 15-month vaccinations, all active pain interventions were administered (video and sucrose and lidocaine); however, individuals remained blinded to the original treatments given. Pain at 15 months was evaluated during 3 procedure phases (baseline, needle injection, and recovery) by a researcher unaware of group allocation using a validated measure, the Modified Behavioural Pain Scale (range, 0-10). Altogether, 352 infants participated; characteristics did not differ among groups (P > .05). Pain scores did not differ among groups during baseline (P = .642), needle injection (P = .739), or recovery (P = .750) phases. In conclusion, there was no evidence of a long-term benefit of consistent use of pain interventions in the first year of life on future infant pain responsivity at 15-month vaccinations.Perspective: This randomized controlled trial did not find a long-term benefit of consistent pain management during infant vaccinations on future infant pain responsivity at 15 months. The results are relevant to clinicians and researchers studying and evaluating pain interventions in children undergoing medical procedures. [ABSTRACT FROM AUTHOR]

Background: Improved diagnostics for typhoid are needed; a typhoid controlled human infection model may accelerate their development and translation. Here, we evaluated a blood culture-PCR assay for detecting infection after controlled human infection with S. Typhi and compared test performance with optimally performed blood cultures.Methodology/principal Findings: Culture-PCR amplification of blood samples was performed alongside daily blood culture in 41 participants undergoing typhoid challenge. Study endpoints for typhoid diagnosis (TD) were fever and/or bacteraemia. Overall, 24/41 (59%) participants reached TD, of whom 21/24 (86%) had ≥1 positive blood culture (53/674, 7.9% of all cultures) or 18/24 (75%) had ≥1 positive culture-PCR assay result (57/684, 8.3%). A further five non-bacteraemic participants produced culture-PCR amplicons indicating infection; overall sensitivity/specificity of the assay compared to the study endpoints were 70%/65%. We found no significant difference between blood culture and culture-PCR methods in ability to identify cases (12 mismatching pairs, p = 0.77, binomial test). Clinical and stool culture metadata demonstrated that additional culture-PCR amplification positive individuals likely represented true cases missed by blood culture, suggesting the overall attack rate may be 30/41 (73%) rather than 24/41 (59%). Several participants had positive culture-PCR results soon after ingesting challenge providing new evidence for occurrence of an early primary bacteraemia.Conclusions/significance: Overall the culture-PCR assay performed well, identifying extra typhoid cases compared with routine blood culture alone. Despite limitations to widespread field-use, the benefits of increased diagnostic yield, reduced blood volume and faster turn-around-time, suggest that this assay could enhance laboratory typhoid diagnostics in research applications and high-incidence settings. [ABSTRACT FROM AUTHOR]

Background: We sought to develop an improved 12 lead ECG model to diagnose hyperkalemia by use of traditional and novel parameters.Methods: We retrospectively analyzed ECGs in consecutive hyperkalemic patients (serum potassium (K)>5.3mEq/L) by blinded investigators with normokalemic ECGs as internal controls. Potassium levels were modeled using general linear mixed models followed by refit with standardized variables. Optimum sensitivity and specificity were determined using cut point analysis of ROC-AUC.Results: The training set included 236 ECGs (84 patients) and validation set 97 ECGs (23 patients). Predicted K=(5.2354)+(0.03434*descending T slope)+(-0.2329*T width)+(-0.9652*reciprocal of new QRS width>100msec). ROC-AUC in the validation set was 0.78 (95% CI 0.69-0.88). Maximum specificity of the model was 84% for K>5.91 with sensitivity of 63%.Conclusion: ECG model incorporating T-wave width, descending T-wave slope and new QRS prolongation improved hyperkalemia diagnosis over traditional ECG analysis. [ABSTRACT FROM AUTHOR]

Due to its low cost, biocompatibility and slow bioresorption, poly-ε-caprolactone (PCL) continues to be a suitable material for select biomedical engineering applications. We used a combined atomic force microscopy (AFM)/optical microscopy technique to determine key mechanical properties of individual electrospun PCL nanofibers with diameters between 440–1040 nm. Compared to protein nanofibers, PCL nanofibers showed much lower adhesion, as they slipped on the substrate when mechanically manipulated. We, therefore, first developed a novel technique to anchor individual PCL nanofibers to micrometer-sized ridges on a substrate, and then mechanically tested anchored nanofibers. When held at constant strain, tensile stress relaxed with fast and slow relaxation times of 1.0 ± 0.3 s and 8.8 ± 3.1 s, respectively. The total tensile modulus was 62 ± 26 MPa, the elastic (non-relaxing) component of the tensile modulus was 53 ± 36 MPa. Individual PCL fibers could be stretched elastically (without permanent deformation) to strains of 19–23%. PCL nanofibers are rather extensible; they could be stretched to a strain of at least 98%, and a tensile strength of at least 12 MPa, before they slipped off the AFM tip. PCL nanofibers that had aged for over a month at ambient conditions became stiffer and less elastic. Our technique provides accurate nanofiber mechanical data, which are needed to guide construction of scaffolds for cells and other biomedical devices. [ABSTRACT FROM AUTHOR]

Most studies of road dust composition have sampled a very wide range of particle sizes, but from the perspective of respiratory exposure to resuspended dusts, it is the PM 10 fraction which is of most importance. The PM 10 fraction of road dust samples was collected at two sites in Birmingham, UK (major highway and road tunnel) and one site in New Delhi, India. Dust loadings were found to be much higher for New Delhi compared to Birmingham, while concentrations of several species were much higher in the case of Birmingham. Detailed chemical source profiles were prepared for both cities and previously generated empirical factors for source attribution to brake wear, tyre wear, and crustal dust were successfully applied to the UK sites. However, 100% of the mass for the Indian site could not be accounted for using these factors. This study highlights the need for generation of local empirical estimation factors for non-exhaust vehicle emissions. A limited number of bulk road dust and brake pad samples were also characterized. Oxidative potential (OP) was also determined for a limited number of PM 10 and bulk road dust samples, and Cu was found to be a factor significantly associated with OP in PM 10 and bulk road dust. [ABSTRACT FROM AUTHOR]

Introduction Assessment on human papillomavirus (HPV) testing and disease outcome of atypical squamous cell, cannot exclude high grade squamous intraepithelial lesion (ASC-H) in different age groups is limited in published reports. We reviewed our experience over a 5-year period on ASC-H cytology and correlated age distribution with high-risk HPV (HR-HPV) status and histological follow-up in a large cohort study. Materials and methods Women with ASC-H cytology were retrieved from the hospital database. HR-HPV status and histological diagnoses on cervical biopsy or loop electrosurgical excisional procedure specimens were reviewed and correlated to 5 age groups. Results Ages of women with ASC-H ranged from 16 to 88 years, with 42% women <30 years and 58% women >30 years. Among 647 cases diagnosed as ASC-H, 96% (618) had HR-HPV testing results, including 68.2% HR-HPV positive and 31.8% HR-HPV negative. HR-HPV positivity of ASC-H gradually decreased from 95.2% in women <20 years to 40.6% in the age group >51 years. Histologic follow-ups were available for review in 80% (517) of the cases. Cervical intraepithelial neoplasia, grade 2 or higher (CIN2+) lesions were found in 40.3% (208) cases, including 92.9% women with HR-HPV-positive/ASC-H and 7.1% of women with HR-HPV-negative/ASC-H. The detection rate of CIN2+ by ASC-H gradually decreased from 51.2% in women <20 years to 18.2% in women >51 years. The majority of postmenopausal women with HR-HPV-negative/ASC-H had atrophy-related change. Conclusions The specificity of ASC-H cytology in detection of cervical CIN2+ lesions is age-dependent: higher in younger women <30 years, but gradually decreased in women >30 years. The vast majority (93%) of CIN2+ lesions were seen women with HR-HPV-positive/ASC-H. HR-HPV testing improves the accuracy and specificity in women with ASC-H in almost all age groups, especially in age groups older than 40 years. [ABSTRACT FROM AUTHOR]

Protein based polymers provide an exciting and complex landscape for tunable natural biomaterials through modulation of molecular level interactions. Here we demonstrate the ability to modify protein polymer structural and mechanical properties at multiple length scales by molecular ‘interference’ of fibrin's native polymerization mechanism. We have previously reported that engagement of fibrin's polymerization ‘ hole b ’, also known as ‘b-pockets’, through PEGylated complementary ‘ knob B ’ mimics can increase fibrin network porosity but also, somewhat paradoxically, increase network stiffness. Here, we explore the possible mechanistic underpinning of this phenomenon through characterization of the effects of knob B -fibrin interaction at multiple length scales from molecular to bulk polymer. Despite its weak monovalent binding affinity for fibrin, addition of both knob B and PEGylated knob B at concentrations near the binding coefficient, K d , increased fibrin network porosity, consistent with the reported role of knob B-hole b interactions in promoting lateral growth of fibrin fibers. Addition of PEGylated knob B decreases the extensibility of single fibrin fibers at concentrations near its K d but increases extensibility of fibers at concentrations above its K d . The data suggest this bimodal behavior is due to the individual contributions knob B , which decreases fiber extensibility, and PEG, which increase fiber extensibility. Taken together with laser trap-based microrheological and bulk rheological analyses of fibrin polymers, our data strongly suggests that hole b engagement increases in single fiber stiffness that translates to higher storage moduli of fibrin polymers despite their increased porosity. These data point to possible strategies for tuning fibrin polymer mechanical properties through modulation of single fiber mechanics. [ABSTRACT FROM AUTHOR]

A synthesis of protected homochiral tetrahydropteridines from (2 S )-malic acid has been developed. This presents methodology for the synthesis of reduced pteridine coenzymes and pharmaceuticals. [ABSTRACT FROM AUTHOR]

The prevalence of polymyxin-resistant Enterobacteriaceae is increasing worldwide. Their emergence is worrisome and limits therapeutic options for severely ill patients. We aimed to investigate the molecular and epidemiological characteristics of polymyxin-resistant Klebsiella pneumoniae circulating in Brazilian hospitals. Polymyxin-resistant K. pneumoniae isolates from two Brazilian healthcare facilities were characterized phenotypically and subjected to whole genome sequencing (WGS). Using the WGS data we determined their sequence type, resistance gene content (resistome), their composition of virulence genes and plasmids. ST11 was the most common (80 %) sequence type among the isolates followed by ST345, ST15 and ST258. A resistome analysis revealed the common presence of bla KPC-2 and less frequently bla SHV-11 , bla TEM-1 , bla CTX-M-15 , and bla OXA-9. Genes conferring resistance to aminoglycosides, fluoroquinolones, phenicols, sulphonamides, tetracyclines, trimethoprim and macrolide-lincosamide-streptogramin were also detected. We observed a clonal spread of polymyxin-resistant K. pneumoniae isolates, with polymyxin-resistance associated with various alterations in the mgrB gene including inactivation by an insertion sequence and nonsense point mutations. We additionally identified a novel 78-bp repeat sequence, encoding a MgrB protein with 26 amino acids duplicated in six isolates. This is the first observation of this type of alteration being associated with polymyxin resistance. Our findings demonstrate that mgrB alterations were the most common source of polymyxin-resistance in Brazilian clinical settings. Interestingly, distinct genetic events were identified among clonally related isolates, including a new amino acid alteration. The clinical implications and investigation of the resistance mechanisms is of great importance to patient safety and control of these infections, particularly in long-term care facilities. [ABSTRACT FROM AUTHOR]

• Several risk factors were associated with polymyxin-resistant strains. • The mortality rate was significantly higher in patients with polymyxin-resistant strains. • Carbapenem exposure was strongly associated with mortality. • Aminoglycoside use was a protection factor against mortality from polymyxin-resistant strains. • Polymyxin resistance occurred through mutational changes in mgrB, phoPQ and soxS genes. This study aimed to assess the clinical impact and potential risk factors associated with polymyxin-resistant Enterobacteriaceae strains isolated from patients hospitalized in adult and neonatal intensive care units. A case–control study was conducted from September 2015 to January 2017. Antimicrobial susceptibility of polymyxin-resistant Enterobacteriaceae strains was determined by broth microdilution. The presence of resistance genes was evaluated by polymerase chain reaction and DNA sequencing. Renal failure [ P =0.02, odds ratio (OR) 11.37, 95% confidence interval (CI) 1.0–128.63], use of a urinary catheter (P <0.01, OR 4.16, 95% CI 38.82–366.07), transfer between hospital units (P =0.03, OR 9.98, 95% CI 1.01–98.42), carbapenem use (P <0.01, OR 45.49, 95% CI 6.93–298.62) and surgical procedure (P <0.01, OR 16.52, 95% CI 2.83–96.32) were found to be risk factors for the acquisition of polymyxin-resistant strains in adult patients. For neonatal patients, use of a central venous catheter (P <0.01, OR 69.59, 95% CI 7.33–660.30) was the only risk factor associated with the acquisition of polymyxin-resistant strains. Analysis of the outcomes revealed that the mortality rate was significantly higher in adult (66.6%) and neonatal (23.5%) patients with polymyxin-resistant strains than in those with polymyxin-susceptible strains. In addition, carbapenem exposure (P <0.01, OR 50.93, 95% CI 2.26–>999.999) was strongly associated with mortality. On the other hand, aminoglycoside use (P <0.03, OR 0.06, 95% CI 0.004–0.97) was a protective factor against mortality from polymyxin-resistant strains. Several risk factors were associated with polymyxin-resistant strains. The high mortality rates showed that acquisition of these strains is a predictor for unfavourable outcomes. Combination treatment with an aminoglycoside and polymyxin might be a better combination to improve patient outcomes. [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]

Typhoid (enteric fever) remains a major cause of morbidity and mortality worldwide, causing over 21 million new infections annually, with the majority of deaths occurring in young children. Because typhoid fever-causing Salmonella have no known environmental reservoir, the chronic, asymptomatic carrier state is thought to be a key feature of continued maintenance of the bacterium within human populations. Despite the importance of this disease to public health, our understanding of the molecular mechanisms that catalyze carriage, as well as our ability to reliably identify and treat the Salmonella carrier state, have only recently begun to advance. [ABSTRACT FROM AUTHOR]

Background: The burden and influence of health-care associated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is unknown. We aimed to examine the use of rapid SARS-CoV-2 sequencing combined with detailed epidemiological analysis to investigate health-care associated SARS-CoV-2 infections and inform infection control measures.Methods: In this prospective surveillance study, we set up rapid SARS-CoV-2 nanopore sequencing from PCR-positive diagnostic samples collected from our hospital (Cambridge, UK) and a random selection from hospitals in the East of England, enabling sample-to-sequence in less than 24 h. We established a weekly review and reporting system with integration of genomic and epidemiological data to investigate suspected health-care associated COVID-19 cases.Findings: Between March 13 and April 24, 2020, we collected clinical data and samples from 5613 patients with COVID-19 from across the East of England. We sequenced 1000 samples producing 747 high-quality genomes. We combined epidemiological and genomic analysis of the 299 patients from our hospital and identified 35 clusters of identical viruses involving 159 patients. 92 (58%) of 159 patients had strong epidemiological links and 32 (20%) patients had plausible epidemiological links. These results were fed back to clinical, infection control, and hospital management teams, leading to infection-control interventions and informing patient safety reporting.Interpretation: We established real-time genomic surveillance of SARS-CoV-2 in a UK hospital and showed the benefit of combined genomic and epidemiological analysis for the investigation of health-care associated COVID-19. This approach enabled us to detect cryptic transmission events and identify opportunities to target infection-control interventions to further reduce health-care associated infections. Our findings have important implications for national public health policy as they enable rapid tracking and investigation of infections in hospital and community settings.Funding: COVID-19 Genomics UK funded by the Department of Health and Social Care, UK Research and Innovation, and the Wellcome Sanger Institute. [ABSTRACT FROM AUTHOR]

This report describes a technique for an immediate mechanical intervention using a familiar tool for emergency physicians and trauma surgeons to temporize acute epidural bleeding with mass effect. The Monro-Kellie Doctrine suggests that immediate removal of some blood will reduce intracranial pressure and mitigate some of the deleterious effects until the neurosurgeon can respond. A 38-year-old male with active extradural hemorrhage and expanding hemtoma with mass effect and herniation was treated at the bedside with an intraosseous drill to perform craniostomy and allow serial aspirations of continued bleeding. Bedside craniosotmy with an intraosseous drill can allow for immediate temporizing of a large epidural hemorrhage and be applied by emergency physicians and/or trauma specialists when neurosurgical consultation is delayed. Serial aspirations should be performed when hemorrhage is ongoing and until definitive evacuation is performed. [ABSTRACT FROM AUTHOR]

Constraining the complex refractive indices, optical properties and size of brown carbon (BrC) aerosols is a vital endeavor for improving climate models and satellite retrieval algorithms. Smoldering wildfires are the largest source of primary BrC, and fuel parameters such as moisture content, source depth, geographic origin, and fuel packing density could influence the properties of the emitted aerosol. We measured in situ spectral (375–1047 nm) optical properties of BrC aerosols emitted from smoldering combustion of Boreal and Indonesian peatlands across a range of these fuel parameters. Inverse Lorenz–Mie algorithms used these optical measurements along with simultaneously measured particle size distributions to retrieve the aerosol complex refractive indices ( m = n + i κ). Our results show that the real part n is constrained between 1.5 and 1.7 with no obvious functionality in wavelength (λ), moisture content, source depth, or geographic origin. With increasing λ from 375 to 532 nm, κ decreased from 0.014 to 0.003, with corresponding increase in single scattering albedo (SSA) from 0.93 to 0.99. The spectral variability of κ follows the Kramers-Kronig dispersion relation for a damped harmonic oscillator. For λ ≥ 532 nm, both κ and SSA showed no spectral dependency. We discuss differences between this study and previous work. The imaginary part κ was sensitive to changes in FPD, and we hypothesize mechanisms that might help explain this observation. [ABSTRACT FROM AUTHOR]

It is predicted that the integration of climate-based early warning systems into existing action plans will facilitate the timely provision of interventions to diarrheal disease epidemics in resource-poor settings. Diarrhea remains a considerable public health problem in Ho Chi Minh City (HCMC), Vietnam and we aimed to quantify variation in the impact of environmental conditions on diarrheal disease risk across the city. Using all inpatient diarrheal admissions data from three large hospitals within HCMC, we developed a mixed effects regression model to differentiate district-level variation in risk due to environmental conditions from the overarching seasonality of diarrheal disease hospitalization in HCMC. We identified considerable spatial heterogeneity in the risk of all-cause diarrhea across districts of HCMC with low elevation and differential responses to flooding, air temperature, and humidity driving further spatial heterogeneity in diarrheal disease risk. The incorporation of these results into predictive forecasting algorithms will provide a powerful resource to aid diarrheal disease prevention and control practices in HCMC and other similar settings. [ABSTRACT FROM AUTHOR]

Summary Objectives Previous studies indicate a high burden of diarrhoeal disease in Vietnamese children, however longitudinal community-based data on burden and aetiology are limited. The findings from a large, prospective cohort study of diarrhoeal disease in infants in southern Vietnam are presented herein. Methods Infants were enrolled at birth in urban Ho Chi Minh City and a semi-rural district in southern Vietnam, and followed for 12 months ( n = 6706). Diarrhoeal illness episodes were identified through clinic-based passive surveillance, hospital admissions, and self-reports. Results The minimum incidence of diarrhoeal illness in the first year of life was 271/1000 infant-years of observation for the whole cohort. Rotavirus was the most commonly detected pathogen (50% of positive samples), followed by norovirus (24%), Campylobacter (20%), Salmonella (18%), and Shigella (16%). Repeat infections were identified in 9% of infants infected with rotavirus, norovirus, Shigella, or Campylobacter, and 13% of those with Salmonella infections. Conclusions The minimum incidence of diarrhoeal disease in infants in both urban and semi-rural settings in southern Vietnam was quantified prospectively. A large proportion of laboratory-diagnosed disease was caused by rotavirus and norovirus. These data highlight the unmet need for a rotavirus vaccine in Vietnam and provide evidence of the previously unrecognized burden of norovirus in infants. [ABSTRACT FROM AUTHOR]

Introduction Patients frequently turn to the Internet when seeking answers to healthcare related inquiries including questions about the effects of radiation when undergoing radiologic studies. We investigate the readability of online patient education materials concerning radiation safety from multiple Internet resources. Methods Patient education material regarding radiation safety was downloaded from 8 different websites encompassing: (1) the Centers for Disease Control and Prevention, (2) the Environmental Protection Agency, (3) the European Society of Radiology, (4) the Food and Drug Administration, (5) the Mayo Clinic, (6) MedlinePlus, (7) the Nuclear Regulatory Commission, and (8) the Society of Pediatric Radiology. From these 8 resources, a total of 45 articles were analyzed for their level of readability using 10 different readability scales. Results The 45 articles had a level of readability ranging from 9.4 to the 17.2 grade level. Only 3/45 (6.7%) were written below the 10th grade level. No statistical difference was seen between the readability level of the 8 different websites. Conclusions All 45 articles from all 8 websites failed to meet the recommendations set forth by the National Institutes of Health and American Medical Association that patient education resources be written between the 3rd and 7th grade level. Rewriting the patient education resources on radiation safety from each of these 8 websites would help many consumers of healthcare information adequately comprehend such material. [ABSTRACT FROM AUTHOR]

Nontyphoidal Salmonella (NTS) are associated with both diarrhea and bacteremia. Antimicrobial resistance (AMR) is common in NTS in low-middle income countries, but the major source(s) of AMR NTS in humans are not known. Here, we aimed to assess the role of animals as a source of AMR in human NTS infections in Vietnam. We retrospectively combined and analyzed 672 NTS human and animal isolates from four studies in southern Vietnam and compared serovars, sequence types (ST), and AMR profiles. We generated a population structure of circulating organisms and aimed to attribute sources of AMR in NTS causing invasive and noninvasive disease in humans using Bayesian multinomial mixture models. Among 672 NTS isolates, 148 (22%) originated from human blood, 211 (31%) from human stool, and 313 (47%) from animal stool. The distribution of serovars, STs, and AMR profiles differed among sources; serovars Enteritidis, Typhimurium, and Weltevreden were the most common in human blood, human stool, and animals, respectively. We identified an association between the source of NTS and AMR profile; the majority of AMR isolates were isolated from human blood (p < 0.001). Modelling by ST-AMR profile found chickens and pigs were likely the major sources of AMR NTS in human blood and stool, respectively; but unsampled sources were found to be a major contributor. Antimicrobial use in food animals is hypothesized to play role in the emergence of AMR in human pathogens. Our cross-sectional population-based approach suggests a significant overlap between AMR in NTS in animals and humans, but animal NTS does explain the full extent of AMR in human NTS infections in Vietnam. • The major source(s) of antimicrobial resistance (AMR) in nontyphoidal Salmonella (NTS) are unknown. • We analyzed 672 NTS isolates, 148 (41%) from human blood, 211 (59%) from human stool, and 136 (43%) from animal stool. • Enteritidis, Typhimurium, and Weltevreden were the common serovars in human blood, human stool, and animals, respectively. • The majority of AMR isolates were associated with human blood. • NTS from animals does explain the full extent of AMR in human NTS infections. [ABSTRACT FROM AUTHOR]

We investigated antimicrobial residues, non-typhoidal Salmonella (NTS), Vibrio spp. and their associated antimicrobial resistance (AMR), in shrimps locally purchased in Ho Chi Minh City (Vietnam). In addition, we investigated the relationship between AMR in NTS, Vibrio spp. and antimicrobial residue in the same sample. A total of 40 samples of shrimp heads/shells from different retail sources was cultured using ISO 6579–1:2017 (NTS) and ISO/TS 21872–1:2007 (Vibrio spp.). Phenotypic antimicrobial susceptibility was investigated using Vitek (NTS, 34 antimicrobials) and disk diffusion (Vibrio spp., 12 antimicrobials). A total of 9 (22.5%) samples contained antimicrobial residue, including tetracyclines, fluoroquinolones, sulfonamides and macrolides (in 7.5%, 7.5%, 2.5% and 2.5% of samples, respectively). Shrimp samples from supermarkets had a higher prevalence of antimicrobial residue than those purchased in street markets (50% vs. 13.3%) (p = 0.049). A total of 30 (75%) samples were contaminated with NTS. All samples contained Vibrio spp., with V. parahaemolyticus being most common (87.5% samples). A total of 58.9% NTS isolates were multidrug resistant. With regards to the highest priority, critically important antimicrobials, the highest resistance corresponded to quinolones (14.4–47.8%), followed by 3rd and 4th generation cephalosporins (3.3–7.8%). Vibrio spp. isolates were characterised by their high resistance against ampicillin (82.7%) and 3rd generation cephalosporins (8.3–16.5%). Extended Spectrum Beta-Lactamase (ESBL) activity was detected in 28.1% V. parahaemolyticus isolates. Half of ESBL-positive V. parahaemolyticus strains harboured bla CTX-M1. We found an association between the presence of residues and the number of resistances for NTS (p = 0.075) and Vibrio spp. isolates (p = 0.093) from the same sample. These findings suggest that the presence of residues may contribute to the selection of AMR in foodborne pathogens in shrimps. Authorities should strengthen policies aiming at restricting inappropriate antimicrobial usage in shrimp farming, and step up monitoring of antimicrobial residues and food-borne pathogens at retail in Vietnam. • Highest prevalence of antimicrobial residues found in shrimps from supermarkets. • 75% samples were contaminated with non-typhoidal Salmonella (NTS). • Isolates from samples with antimicrobial residues had highest prevalence of phenotypic resistance. • Extended Spectrum Beta-Lactamase activity detected in 28.1% V. parahaemolyticus isolates. [ABSTRACT FROM AUTHOR]