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The genus Enterococcus includes two Gram-positive pathogens of particular clinical relevance: E. faecalis and E. faecium. Infections with each of these pathogens are becoming more frequent, particularly in the case of hospital-acquired infections. Like most other bacterial species of clinical importance, antimicrobial resistance (and, specifically, multi-drug resistance) is an increasing threat, with both species considered to be of particular importance by the World Health Organization and the US Centers for Disease Control. The threat of antimicrobial resistance is exacerbated by the staggering difference in the speeds of development for the discovery and development of the antimicrobials versus resistance mechanisms. In the search for alternative strategies, modulation of host-pathogen interactions in general, and virulence inhibition in particular, have drawn substantial attention. Unfortunately, these approaches require a fairly comprehensive understanding of virulence determinants. This requirement is complicated by the fact that enterococcal infection models generally require vertebrates, making them slow, expensive, and ethically problematic, particularly when considering the thousands of animals that would be needed for the early stages of experimentation. To address this problem, we developed the first high-throughput C. elegans–E. faecium infection model involving host death. Importantly, this model recapitulates many key aspects of murine peritonitis models, including utilizing similar virulence determinants. Additionally, host death is independent of peroxide production, unlike other E. faecium–C. elegans virulence models, which allows the assessment of other virulence factors. Using this system, we analyzed a panel of lab strains with deletions of targeted virulence factors. Although removal of certain virulence factors (e.g., Δfms15) was sufficient to affect virulence, multiple deletions were generally required to affect pathogenesis, suggesting that host-pathogen interactions are multifactorial. These data were corroborated by genomic analysis of selected isolates with high and low levels of virulence. We anticipate that this platform will be useful for identifying new treatments for E. faecium infection.

Detecting autoantibodies provides foundational information for the diagnosis of most autoimmune diseases. An important pathophysiological distinction is whether autoantibodies are directed against extracellular or intracellular proteins. Autoantibodies targeting extracellular domains of proteins, such as membrane receptors, channels or secreted molecules are often directly pathogenic, whereby autoantibody binding to the autoantigen disrupts the normal function of a critical protein or pathway, and/or triggers antibody-dependent cell surface complement killing. By comparison, autoantibodies directed against intracellular proteins are recognized as useful diagnostic biomarkers of abnormal autoimmune activity, but the link between antigenicity and pathogenicity is less straightforward. Because intracellular autoantigens are generally inaccessible to autoantibody binding, for the most part, they do not directly contribute to pathogenesis. In a few diseases, autoantibodies to intracellular targets cause damage indirectly by immune complex formation, immune activation, and other processes. In this review, the general features of and differences between autoimmune diseases segregated on the basis of intracellular or extracellular autoantigens are explored using over twenty examples. Expression profiles of autoantigens in relation to the tissues targeted by autoimmune disease and the temporal appearance of autoantibodies before clinical diagnosis often correlate with whether the respective autoantibodies mostly recognize either intracellular or extracellular autoantigens. In addition, current therapeutic strategies are discussed from this vantage point. One drug, rituximab, depletes CD20+ B-cells and is highly effective for autoimmune disorders associated with autoantibodies against extracellular autoantigens. In contrast, diseases associated with autoantibodies directed predominately against intracellular autoantigens show much more complex immune cell involvement, such as T-cell mediated tissue damage, and require different strategies for optimal therapeutic benefit. Understanding the clinical ramifications of autoimmunity derived by autoantibodies against either intracellular or extracellular autoantigens, or a spectrum of both, has practical implications for guiding drug development, generating monitoring tools, stratification of patient interventions, and designing trials based on predictive autoantibody profiles for autoimmune diseases.

Multiple breath nitrogen washout (MBNW) quantifies ventilation heterogeneity. Two distinct protocols are currently used for MBNW testing: “controlled breathing”, with targeted tidal volume (VT) and respiratory rate (RR); and “free breathing”, with no constraints on breathing pattern. Indices derived from the two protocols (functional residual capacity (FRC), lung clearance index (LCI), Scond, Sacin) have not been directly compared in adults. We aimed to determine whether MBNW indices are comparable between protocols, to identify factors underlying any between-protocol differences and to determine the between-session variabilities of each protocol. We performed MBNW testing by both protocols in 27 healthy adult volunteers, applying the currently proposed correction for VT to Scond and Sacin derived from free breathing. To establish between-session variability, we repeated testing in 15 volunteers within 3 months. While FRC was comparable between controlled versus free breathing (3.17 (0.98) versus 3.18 (0.94) L, p=0.88), indices of ventilation heterogeneity derived from the two protocols were not, with poor correlation for Scond (r=0.18, p=0.36) and significant bias for Sacin (0.057 (0.021) L−1 versus 0.085 (0.038) L−1, p=0.0004). Between-protocol differences in Sacin were related to differences in the breathing pattern, i.e. VT (p=0.004) and RR (p=0.01), rather than FRC. FRC and LCI showed good between-session repeatability, but Scond and Sacin from free breathing showed poor repeatability with wide limits of agreement. These findings have implications for the ongoing clinical implementation of MBNW, as they demonstrate that Scond and Sacin from free breathing, despite VT correction, are not equivalent to the controlled breathing protocol. The poor between-session repeatability of Scond during free breathing may limit its clinical utility.

Purpose: To assess failure rate, outcomes, and patient satisfaction in patients who underwent anterior cruciate ligament (ACL) repair with suture augmentation for clinical instability and proximal avulsion of the ACL. Methods: We retrospectively reviewed consecutive suture-augmented ACL repairs performed by a single surgeon between January 2014 and June 2016 for proximal ACL avulsion. Patients were included if they were at least 24 months postoperative from repair surgery. Patients were excluded from the study if they underwent primary ACL reconstruction instead of repair or if they had a concomitant multiligamentous knee injury. Knee Injury and Osteoarthritis Outcome Score (KOOS), visual analog scale (VAS), Veterans RAND-12 (VR-12), Marx Activity, and Single Assessment Numeric Evaluation data were collected. Results: Of 172 patients who underwent ACL surgery between January 2014 and June 2016, 28 (16%) with Sherman type I or II ACL tears or high-grade partial avulsion with clinical instability underwent ACL repair with suture augmentation. One patient was not available for follow-up. The 27 patients were age 27.4 ± 8.6 years, 18 males (66.7%), and 2.8 ± 0.7 years follow-up (range, 2.0-3.8 years). Of these 27 patients, 4 recurrent ACL injuries (14.8%) required revision to reconstruction. The remaining 23 patients had successful ACL repair with no clinical instability and no subjective complaints at final follow-up. Final scores were KOOS 83.7 ± 12.8, Marx 8.6 ± 4.0, VAS 1.1 ± 1.8, physical VR-12 53.6 ± 5.2, mental VR-12 53.1 ± 8.1, and Single Assessment Numeric Evaluation 83.0 ± 12.9. In the 11 patients with baseline data, significant improvements were observed in composite KOOS (50.4 ± 11.5 to 85.7 ± 8.4; P < .001; VAS: 3.9 ± 2.6 to 0.8 ± 0.8; P = .002; and physical VR-12: 39.9 ± 6.5 to 55.5 ± 3.3; P < .001). All 11 patients (100%) met or exceeded the KOOS composite minimum clinically important difference (mean 34.0 increase). Conclusions: In patients with proximal ACL avulsion, arthroscopic primary ACL repair with suture augmentation demonstrated high functional outcome and improved patient-reported outcomes at 2-year follow-up. The rate of graft failure was 15%. Level of Evidence: Level IV, therapeutic case series.

Chordomas are rare tumors that are notoriously refractory to chemotherapy and radiotherapy when radical surgical resection is not achieved or upon recurrence after maximally aggressive treatment. The study of chordomas has been complicated by small patient cohorts and few available model systems due to the rarity of these tumors. Emerging next-generation sequencing technologies have broadened understanding of this disease by implicating novel pathways for possible targeted therapy. Mutations in cell-cycle regulation and chromatin remodeling genes have been identified in chordomas, but their significance remains unknown. Investigation of the immune microenvironment of these tumors suggests that checkpoint protein expression may influence prognosis, and adjuvant immunotherapy may improve patient outcome. Finally, growing evidence supports aberrant growth factor signaling as potential pathogenic mechanisms in chordoma. In this review, we characterize the impact on treatment opportunities offered by the genomic and immunologic landscape of this tumor.

Abstract Background Changes in diet and exercise can alter the gut microbiome of humans and mice; however, few studies to date have assessed the microbiomes of highly fit athletes. In this pilot study, we used metagenomic whole genome shotgun (mWGS) and metatranscriptomic (RNA-Seq) sequencing to show what organisms are both present and active in the gut microbiomes of both professional and amateur level competitive cyclists and to determine if any significant differences exist between these two groups. Results Using mWGS sequencing data, we showed that the gut microbiomes of 33 cyclists split into three taxonomic clusters, characterized by either high Prevotella, high Bacteroides or a mix of many genera including Bacteroides, Prevotella, Eubacterium, Ruminococcus, and Akkermansia. While no significant correlations could be found between taxonomic cluster and being either a professional or amateur level cyclist, high abundance of the genus Prevotella (≥2.5%) was significantly correlated with time reported exercising during an average week. Increased abundance of Prevotella was correlated with a number of amino acid and carbohydrate metabolism pathways, including branched chain amino acid metabolism. Further analysis of the metatranscriptome revealed significant taxonomic differences when compared to the metagenome. There was increased abundance of Methanobrevibacter smithii transcripts in a number of professional cyclists in comparison to amateur cyclists and this archaeon had upregulation of genes involved in the production of methane. Furthermore, when methane metabolism was upregulated, there was similar upregulation of energy and carbohydrate metabolism pathways. Conclusions These results provide a framework for common constituents of the gut community in individuals who follow an exercise-rich lifestyle. These data also suggest how certain organisms such as M. smithii may beneficially influence the metabolic efficiency of the gut community in professional cyclists due to synergistic metabolic cross-feeding events.

Silicon quantum dots provide a promising platform for quantum computing based on manipulation of electron degrees of freedom in a well-characterized environment. Here, the authors demonstrate coherent control of electron valley states, yielding an accurate determination of the valley splitting.

Background: The vast majority of pituitary tumors are benign and behave accordingly; however, a fraction are invasive and are more aggressive, with a very small fraction being frankly malignant. The cellular pathways that drive transformation in pituitary neoplasms are poorly characterized, and current classification methods are not reliable correlates of clinical behavior. Novel techniques in epigenetics, the study of alterations in gene expression without changes to the genetic code, provide a new dimension to characterize tumors, and may hold implications for prognostication and management.Methods: We conducted a review of primary epigenetic studies of pituitary tumors with a focus on histone modification, DNA methylation, and transcript modification.Results: High levels of methylation have been identified in invasive and large pituitary tumors. DNA methyltransferase overexpression has been detected in pituitary tumors, especially in macroadenomas. Methylation differences at CpG sites in promoter regions may distinguish several types of tumors from normal pituitary tissue. Histone modifications have been linked to increased p53 expression and longer progression-free survival in pituitary tumors; sirtuins are expressed at higher values in GH-expressing compared to nonfunctional adenomas and correlate inversely with size in somatotrophs. Upregulation in citrullinating enzymes may be an early pathogenic marker of prolactinomas. Numerous genes involved with cell growth and signaling show altered methylation status for pituitary tumors, including cell cycle regulators, components of signal transduction pathways, apoptotic regulators, and pituitary developmental signals.Conclusions: The limited clinical predictive capacity of the current pituitary tumor classification system suggests that tumor subclasses likely remain to be discovered. Ongoing epigenetic studies could provide a basis for adding methylation and/or acetylation screening to standard pituitary tumor workups. Identifying robust correlations between tumor epigenetics and corresponding histological, radiographic, and clinical course information could ultimately inform clinical decision-making.

Citation count is an important measure of academic productivity and evidence dissemination. This cross-sectional bibliometric assessment is aimed at identifying predictors of citations of systematic reviews (SRs) published in 2010 in the field of oral implantology. SRs published in the field of oral implantology in the year 2010 in three electronic databases were identified. Following which, data were extracted from selected SRs including number of authors, number of institutions, international collaboration status, number of references, and journal impact factor (JIF). Methodological quality of SR was evaluated separately using the “Assessing the Methodological Quality of Systematic Reviews” (AMSTAR) checklist. Bivariate associations between the extracted variables, including AMSTAR score, and citation count were examined. Simultaneous effect of all extracted variables and SR citation count were examined by a multivariable linear regression model. In the included 26 SRs, the number of authors and institutions ranged from 1 to 8 and 1 to 5, respectively. The JIF was on average 3.22 (±1.81), and the AMSTAR score ranged from 2 to 10. Total citations ranged from 0 to 123 in Web of Science and 1 to 245 in Google Scholar. Our analysis revealed a lack of significant ( p > .05) correlation between the extracted variables and citation count. No reliable indicator that could predict the citation counts for SRs published in 2010 in oral implantology was identified. Of importance was the lack of significant correlation between AMSTAR score and citation count, which underscores the importance of careful appraisal of SR before incorporating its findings in clinical practice.

PurposeGlaucoma screening can be performed by assessing the vertical-cup-to-disk ratio (VCDR) of the optic nerve head from fundus photography, but VCDR grading is inherently subjective. This study investigated whether computer software could improve the accuracy and repeatability of VCDR assessment.MethodsIn this cross-sectional diagnostic accuracy study, 5 ophthalmologists independently assessed the VCDR from a set of 200 optic disk images, with the median grade used as the reference standard for subsequent analyses. Eight non-ophthalmologists graded each image by two different methods: by visual inspection and with assistance from a custom-made publicly available software program. Agreement with the reference standard grade was assessed for each method by calculating the intraclass correlation coefficient (ICC), and the sensitivity and specificity determined relative to a median ophthalmologist grade of ≥0.7.ResultsVCDR grades ranged from 0.1 to 0.9 for visual assessment and from 0.1 to 1.0 for software-assisted grading, with a median grade of 0.4 for each. Agreement between each of the 8 graders and the reference standard was higher for visual inspection (median ICC 0.65, interquartile range 0.57 to 0.82) than for software-assisted grading (median ICC 0.59, IQR 0.44 to 0.71); P = 0.02, Wilcoxon signed-rank test). Visual inspection and software assistance had similar sensitivity and specificity for detecting glaucomatous cupping.ConclusionThe computer software used in this study did not improve the reproducibility or validity of VCDR grading from fundus photographs compared with simple visual inspection. More clinical experience was correlated with higher agreement with the ophthalmologist VCDR reference standard.

The use of drones to study marine animals shows promise for the examination of numerous aspects of their ecology, behaviour, health and movement patterns. However, the responses of some marine phyla to the presence of drones varies broadly, as do the general operational protocols used to study them. Inconsistent methodological approaches could lead to difficulties comparing studies and can call into question the repeatability of research. This review draws on current literature and researchers with a wealth of practical experience to outline the idiosyncrasies of studying various marine taxa with drones. We also outline current best practice for drone operation in marine environments based on the literature and our practical experience in the field. The protocols outlined herein will be of use to researchers interested in incorporating drones as a tool into their research on marine animals and will help form consistent approaches for drone-based studies in the future.

Abstract Increasingly complex research questions and global challenges (e.g., climate change and biodiversity loss) are driving rapid development, refinement, and uses of technology in ecology. This trend is spawning a distinct sub‐discipline, here termed “technoecology.” We highlight recent ground‐breaking and transformative technological advances for studying species and environments: bio‐batteries, low‐power and long‐range telemetry, the Internet of things, swarm theory, 3D printing, mapping molecular movement, and low‐power computers. These technologies have the potential to revolutionize ecology by providing “next‐generation” ecological data, particularly when integrated with each other, and in doing so could be applied to address a diverse range of requirements (e.g., pest and wildlife management, informing environmental policy and decision making). Critical to technoecology's rate of advancement and uptake by ecologists and environmental managers will be fostering increased interdisciplinary collaboration. Ideally, such partnerships will span the conception, implementation, and enhancement phases of ideas, bridging the university, public, and private sectors.

ABSTRACT Although the TEM-1 β-lactamase (BlaTEM-1) hydrolyzes penicillins and narrow-spectrum cephalosporins, organisms expressing this enzyme are typically susceptible to β-lactam/β-lactamase inhibitor combinations such as piperacillin-tazobactam (TZP). However, our previous work led to the discovery of 28 clinical isolates of Escherichia coli resistant to TZP that contained only blaTEM-1. One of these isolates, E. coli 907355, was investigated further in this study. E. coli 907355 exhibited significantly higher β-lactamase activity and BlaTEM-1 protein levels when grown in the presence of subinhibitory concentrations of TZP. A corresponding TZP-dependent increase in blaTEM-1 copy number was also observed, with as many as 113 copies of the gene detected per cell. These results suggest that TZP treatment promotes an increase in blaTEM-1 gene dosage, allowing BlaTEM-1 to reach high enough levels to overcome inactivation by the available tazobactam in the culture. To better understand the nature of the blaTEM-1 copy number proliferation, whole-genome sequence (WGS) analysis was performed on E. coli 907355 in the absence and presence of TZP. The WGS data revealed that the blaTEM-1 gene is located in a 10-kb genomic resistance module (GRM) that contains multiple resistance genes and mobile genetic elements. The GRM was found to be tandemly repeated at least 5 times within a p1ESCUM/p1ECUMN-like plasmid when bacteria were grown in the presence of TZP. IMPORTANCE Understanding how bacteria acquire resistance to antibiotics is essential for treating infected patients effectively, as well as preventing the spread of resistant organisms. In this study, a clinical isolate of E. coli was identified that dedicated more than 15% of its genome toward tandem amplification of a ~10-kb resistance module, allowing it to escape antibiotic-mediated killing. Our research is significant in that it provides one possible explanation for clinical isolates that exhibit discordant behavior when tested for antibiotic resistance by different phenotypic methods. Our research also shows that GRM amplification is difficult to detect by short-read WGS technologies. Analysis of raw long-read sequence data was required to confirm GRM amplification as a mechanism of antibiotic resistance.

The availability of low-cost wildlife trackers increases the capacity to collect valuable ecological data when research budgets are limited. We converted a commercially available global positioning system (GPS) product into a low-cost tracking device that sends data via the mobile phone network, and assessed its performance under varying conditions. We established a stationary test, deploying devices along a continuum from open urban areas to topographically and structurally complex forested sites. We tested three features of the device: (a) the GPS, by measuring fix success rate, fix precision and horizontal dilution of precision (HDOP), (b) remote download capacity via the mobile phone network and (c) battery drain. Measures of GPS performance demonstrated high fix success rates and precision. HDOP values were influenced by habitat type and topographical position, but generally remained very low, giving an acceptable degree of error for most applications in wildlife research. Devices experienced delayed data transmission at sites with less phone reception, and faster battery drain at sites with denser vegetation. We recorded device malfunctions in 8.2% of the 110 sampling locations, but these were not associated with habitat type or topography. Our device was effective under a wide range of conditions, and the development process we used provides guidance to other researchers aiming to develop cost-effective wildlife trackers. Reducing the financial and labour costs of acquiring high-quality movement data will improve the capacity to increase sample size in animal movement studies.

Oral cancer continues to be a significant public health problem worldwide. Recently conducted clinical trials demonstrate the ability of black raspberries (BRBs) to modulate biomarkers of molecular efficacy that supports a chemopreventive strategy against oral cancer. However, it is essential that a preclinical animal model of black raspberry (BRB) chemoprevention which recapitulates human oral carcinogenesis be developed, so that we can validate biomarkers and evaluate potential mechanisms of action. We therefore established the ability of BRBs to inhibit oral lesion formation in a carcinogen-induced rat oral cancer model and examined potential mechanisms. F344 rats were administered 4-nitroquinoline 1-oxide (4NQO) (20 µg/ml) in drinking water for 14 weeks followed by regular drinking water for 6 weeks. At week 14, rats were fed a diet containing either 5 or 10% BRB, or 0.4% ellagic acid (EA), a BRB phytochemical. Dietary administration of 5 and 10% BRB reduced oral lesion incidence and multiplicity by 39.3 and 28.6%, respectively. Histopathological analyses demonstrate the ability of BRBs and, to a lesser extent EA, to inhibit the progression of oral cancer. Oral lesion inhibition by BRBs was associated with a reduction in the mRNA expression of pro-inflammatory biomarkers Cxcl1, Mif, and Nfe2l2 as well as the anti-apoptotic and cell cycle associated markers Birc5, Aurka, Ccna1, and Ccna2. Cellular proliferation (Ki-67 staining) in tongue lesions was inhibited by BRBs and EA. Our study demonstrates that, in the rat 4NQO oral cancer model, dietary administration of BRBs inhibits oral carcinogenesis via inhibition of pro-inflammatory and anti-apoptotic pathways.

Purpose. To report a case of bilateral choroidal neovascularization (CNV) in punctate inner choroidopathy (PIC) visualized utilizing optical coherence tomography angiography (OCT-A). Methods. Case report. Results. A 29-year-old woman presented with new visual symptoms in both eyes. Fundoscopic exam revealed bilateral multifocal, small, well-defined lesions consistent with PIC. Optical coherence tomography demonstrated subretinal fluid and retinal pigment epithelium detachments (RPEDs) in both eyes. OCT-A revealed bilateral abnormal increased flow within the RPEDs consistent with CNV. Fluorescein angiography confirmed the presence of bilateral CNV. Conclusion. CNV secondary to PIC may be identified using noninvasive optical coherence tomography angiography.

Summary: Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a devastating pathogen that is associated with high morbidity and mortality worldwide. Livestock are a well-known reservoir for this pathogen, which poses substantial health risks for livestock workers. Little is known about the epidemiology of livestock-associated MRSA (LA-MRSA) among livestock workers in Eastern Europe. Methods: To study the epidemiology of LA-MRSA among swine workers in Romania, we collected and characterized nasal and oropharygneal samples from swine workers on commercial pig farms. A survey that included questions about work-related tasks, biosafety practices, contact with animals, and health status was used to assess the risk factors that were potentially associated with LA-MRSA colonization. Results: The prevalence of MRSA colonization among swine workers was 6.8%. Two LA-MRSA strains with the spa types t034 and t011 and one likely community-associated MRSA strain with the spa type t321 were isolated from workers on five farms. Interestingly, all MRSA carriers worked on farms that imported animals from other production facilities. Conclusion: This is the first study to confirm the presence of LA-MRSA among swine workers in Romania and suggests the need to minimize the risk of LA-MRSA-related infections in swine workers and their community contacts. The findings also suggest a link between the commercial movement of swine and the introduction of LA-MRSA. Keywords: Methicillin-resistant Staphylococcus aureus (MRSA), Antimicrobial resistance, Occupational exposure, Zoonoses, Swine

Condition indices correlating body lipid content with mass and morphometric measurements have been developed for a variety of taxa. However, for many large species, the capture and handling of enough animals to obtain representative population estimates is not logistically feasible. The relatively low cost and reduced disturbance effects of UAVs make them ideal for the rapid acquisition of high volume data for monitoring large species. This study examined the imagery collected from two different UAVs, flown at 25 m altitude, and the subsequent georeferenced orthomosaics as a method for measuring length and axillary girth of Australian fur seals (Arctocephalus pusillus doriferus) to derive an index of body condition. Up to 26% of individuals were orientated correctly (prostrate/sternal recumbent) to allow for body measurements. The UAV-obtained images over-estimated axillary girth diameter due to postural sag on the lateral sides of the thorax while the animals are lying flat in the sternal recumbent position on granite rocks. However, the relationship between axillary girth and standard length was similarly positive for the remotely- and physically-obtained measurements. This indicates that residual values from the remotely-obtained measurements can be used as a relative index of body condition.

The forced oscillation technique (FOT) is gaining clinical acceptance, facilitated by more commercial devices and clinical data. However, the effects of variations in testing protocols used in FOT data acquisition are unknown. We describe the effect of duration of data acquisition on FOT results in subjects with asthma, chronic obstructive pulmonary disease (COPD) and healthy controls. FOT data were acquired from 20 healthy, 22 asthmatic and 18 COPD subjects for 60 s in triplicate. The first 16, 30 and 60 s of each measurement were analysed to obtain total, inspiratory and expiratory resistance of respiratory system (Rrs) and respiratory system reactance (Xrs) at 5 and 19 Hz. With increasing duration, there was a decrease in total and expiratory Rrs for healthy controls, total and inspiratory Rrs for asthmatic subjects and magnitude of total and inspiratory Xrs for COPD subjects at 5 Hz. These decreases were small compared to the differences between clinical groups. Measuring for 16, 30 and 60 s provided ≥3 acceptable breaths in at least 90, 95 and 100% of subjects, respectively. The coefficient of variation for total Rrs and Xrs also decreased with duration. Similar results were found for Rrs and Xrs at 19 Hz. FOT results are statistically, but likely minimally, impacted by acquisition duration in healthy, asthmatic or COPD subjects.

HIV-1 persists as a latent reservoir in people receiving suppressive antiretroviral therapy (ART). When ART is interrupted (treatment interruption/TI), rebound virus re-initiates systemic infection in the lymphoid system. During TI, HIV-1 is also detected in cerebrospinal fluid (CSF), although the source of this rebound virus is unknown. To investigate whether there is a distinct HIV-1 reservoir in the central nervous system (CNS), we compared rebound virus after TI in the blood and CSF of 11 participants. Peak rebound CSF viral loads vary and we show that high viral loads and the appearance of clonally amplified viral lineages in the CSF are correlated with the transient influx of white blood cells. We found no evidence of rebound macrophage-tropic virus in the CSF, even in one individual who had macrophage-tropic HIV-1 in the CSF pre-therapy. We propose a model in which R5 T cell-tropic virus is released from infected T cells that enter the CNS from the blood (or are resident in the CNS during therapy), with clonal amplification of infected T cells and virus replication occurring in the CNS during TI.

This study aimed to characterize Staphylococcus aureus (S. aureus) strains isolated from human infections in Mongolia. Infection samples were collected at two time periods (2007–08 and 2011) by the National Center for Communicable Diseases (NCCD) in Ulaanbaatar, Mongolia. S. aureus isolates were characterized using polymerase chain reaction (PCR) for mecA, PVL, and sasX genes and tested for agr functionality. All isolates were also spa typed. A subset of isolates selected by frequency of spa types was subjected to antimicrobial susceptibility testing and multilocus sequence typing. Among 251 S. aureus isolates, genotyping demonstrated methicillin resistance in 8.8% of isolates (22/251). Approximately 28% of the tested S. aureus isolates were observed to be multidrug resistant (MDR). Sequence type (ST) 154 (spa t667) was observed to be a strain with high virulence potential, as all isolates for this spa type were positive for PVL, had a functional agr system and 78% were MDR. S. aureus isolates of ST239 (spa t037) were observed to cause infections and roughly 60% had functional agr system with a greater proportion being MDR. Additionally, new multilocus sequence types and new spa types were identified, warranting continued surveillance for S. aureus in this region.

In the last decade livestock-associated methicillin-resistant S. aureus (LA-MRSA) has become a public health concern in many parts of the world. Sequence type 398 (ST398) has been the most commonly reported type of LA-MRSA. While many studies have focused on long-term exposure experienced by swine workers, this study focuses on short-term exposures experienced by veterinary students conducting diagnostic investigations. The objectives were to assess the rate of MRSA acquisition and longevity of carriage in students exposed to pork farms and characterize the recovered MRSA isolates. Student nasal swabs were collected immediately before and after farm visits. Pig nasal swabs and environmental sponge samples were also collected. MRSA isolates were identified biochemically and molecularly including spa typing and antimicrobial susceptibility testing. Thirty (30) veterinary students were enrolled and 40 pork farms were visited. MRSA was detected in 30% of the pork farms and in 22% of the students following an exposure to a MRSA-positive pork farm. All students found to be MRSA-positive initially following farm visit were negative for MRSA within 24 hours post visit. Most common spa types recovered were t002 (79%), t034 (16%) and t548 (4%). Spa types found in pork farms closely matched those recovered from students with few exceptions. Resistance levels to antimicrobials varied, but resistance was most commonly seen for spectinomycin, tetracyclines and neomycin. Non-ST398 MRSA isolates were more likely to be resistant to florfenicol and neomycin as well as more likely to be multidrug resistant compared to ST398 MRSA isolates. These findings indicate that MRSA can be recovered from persons visiting contaminated farms. However, the duration of carriage was very brief and most likely represents contamination of nasal passages rather than biological colonization. The most common spa types found in this study were associated with ST5 and expands the range of livestock-associated MRSA types.

In order to examine the prevalence of Staphylococcus aureus on retail pork, three hundred ninety-five pork samples were collected from a total of 36 stores in Iowa, Minnesota, and New Jersey. S. aureus was isolated from 256 samples (64.8%, 95% confidence interval [CI] 59.9%-69.5%). S. aureus was isolated from 67.3% (202/300) of conventional pork samples and from 56.8% (54/95) of alternative pork samples (labeled "raised without antibiotics" or "raised without antibiotic growth promotants"). Two hundred and thirty samples (58.2%, 95% CI 53.2%-63.1%) were found to carry methicillin-sensitive S. aureus (MSSA). MSSA was isolated from 61.0% (183/300) of conventional samples and from 49.5% (47/95) of alternative samples. Twenty-six pork samples (6.6%, 95% CI 4.3%-9.5%) carried methicillin-resistant S. aureus (MRSA). No statistically significant differences were observed for the prevalence of S. aureus in general, or MSSA or MRSA specifically, when comparing pork products from conventionally raised swine and swine raised without antibiotics, a finding that contrasts with a prior study from The Netherlands examining both conventional and "biologic" meat products. In our study spa types associated with "livestock-associated" ST398 (t034, t011) were found in 26.9% of the MRSA isolates, while 46.2% were spa types t002 and t008--common human types of MRSA that also have been found in live swine. The study represents the largest sampling of raw meat products for MRSA contamination to date in the U.S. MRSA prevalence on pork products was higher than in previous U.S.-conducted studies, although similar to that in Canadian studies.