Clinical Ramifications of Bacterial Aggregation in Pleural Fluid.

Bacterial aggregation has been well described to occur in synovial fluid, but it is unknown if bacteria form aggregates in body fluids beyond the synovial fluid. Consequently, this translational study evaluated the ability to form bacterial aggregates in different pleural fluids. Four of the most common causes of thoracic empyema-, , , and -were used here.

Retinal mid-peripheral capillary free zones are enlarged in cognitively unimpaired older adults at high risk for Alzheimer's disease.

Background: Compared to standard neuro-diagnostic techniques, retinal biomarkers provide a probable low-cost and non-invasive alternative for early Alzheimer's disease (AD) risk screening. We have previously quantified the periarteriole and perivenule capillary free zones (mid-peripheral CFZs) in cognitively unimpaired (CU) young and older adults as novel metrics of retinal tissue oxygenation. There is a breakdown of the inner retinal blood barrier, pericyte loss, and capillary non-perfusion or dropout in AD leading to potential enlargement of the mid-peripheral CFZs.

Comparative Evaluation of Current Biochemical-, Sequencing-, and Proteomic-Based Identification Methods for the Streptococcus bovis Group.

The Streptococcus bovis group (previously group D streptococci) consists of seven distinct species and subspecies. Definitive identification within the group is important, as certain organisms have been associated with gastrointestinal carcinoma, bacteremia, infective endocarditis, meningitis, biliary tract disease, and carcinoma, among others. Definitive identification, however, remains elusive due to limitations and inconsistencies across commonly used identification platforms in the United States.

Context-Dependent Roles for Toll-Like Receptors 2 and 9 in the Pathogenesis of Staphylococcus aureus Osteomyelitis.

Staphylococcus aureus is the major causative agent of bacterial osteomyelitis, an invasive infection of bone. Inflammation generated by the immune response to S. aureus contributes to bone damage by altering bone homeostasis.

Retention of Minocycline Susceptibility When Gram-Positive Periprosthetic Joint Infection Isolates Are Non-Susceptible to Doxycycline.

Background: The treatment of hardware infections often utilizes chronic oral suppression antibiotics to prevent infection recurrence. However, when methicillin-resistant and other bacteria are non-susceptible to doxycycline, limited oral antibiotic options can be available that do not cause significant side effects and drug-drug interactions. Consequently, the purpose of this study was to evaluate the ability of Gram-positive clinical prosthetic joint infection isolates that were non-susceptible to doxycycline and to retain susceptibility to minocycline.

The retinal and perceived locus of fixation in the human visual system.

Due to the dramatic difference in spatial resolution between the central fovea and the surrounding retinal regions, accurate fixation on important objects is critical for humans. It is known that the preferred retinal location (PRL) for fixation of healthy human observers rarely coincides with the retinal location with the highest cone density. It is not currently known, however, whether the PRL is consistent within an observer or is subject to fluctuations and, moreover, whether observers' subjective fixation location coincides with the PRL.

Comprehensive Study Identifies a Sensitive, Low-Risk, Closed-System Model for Detection of Fungal Contaminants in Cell and Gene Therapy Products.

The U.S. Food and Drug Administration (FDA) regulates manufacturing and testing of advanced therapeutic medicinal products (ATMPs) to ensure the safety of each product for human use.

Dacron swab and PBS are acceptable alternatives to flocked swab and viral transport media for SARS-CoV-2.

Nasopharyngeal flocked swabs placed in viral transport media (VTM) are the preferred collection methodology for respiratory virus testing. Due to the rapid depletion of available reagents and swabs, we have validated an alternative swab placed in phosphate-buffered saline (PBS) for use in respiratory virus testing in a SARS-CoV-2 real-time polymerase chain reaction assay and a multiplexed respiratory virus panel. We collected nasopharyngeal (NP) swabs and oropharyngeal (OP) swabs from 10 healthy volunteers.

Association of persistent wild-type measles virus RNA with long-term humoral immunity in rhesus macaques.

Recovery from measles results in life-long protective immunity. To understand induction of long-term immunity, rhesus macaques were studied for 6 months after infection with wild-type measles virus (MeV). Infection caused viremia and rash, with clearance of infectious virus by day 14.

MicroLESA: Integrating Autofluorescence Microscopy, In Situ Micro-Digestions, and Liquid Extraction Surface Analysis for High Spatial Resolution Targeted Proteomic Studies.

The ability to target discrete features within tissue using liquid surface extractions enables the identification of proteins while maintaining the spatial integrity of the sample. Here, we present a liquid extraction surface analysis (LESA) workflow, termed microLESA, that allows proteomic profiling from discrete tissue features of ∼110 μm in diameter by integrating nondestructive autofluorescence microscopy and spatially targeted liquid droplet micro-digestion. Autofluorescence microscopy provides the visualization of tissue foci without the need for chemical stains or the use of serial tissue sections.

MyD88 and IL-1R signaling drive antibacterial immunity and osteoclast-driven bone loss during Staphylococcus aureus osteomyelitis.

Staphylococcus aureus is able to infect virtually all organ systems and is a frequently isolated etiologic agent of osteomyelitis, a common and debilitating invasive infection of bone. Treatment of osteomyelitis requires invasive surgical procedures and prolonged antibiotic therapy, yet is frequently unsuccessful due to extensive pathogen-induced bone damage that can limit antibiotic penetration and immune cell influx to the infectious focus. We previously established that S.

Comparing habitual and i. Scription refractions.

Background: Many patients voice concerns regarding poor night vision, even when they see 20/20 or better in the exam room. During mesopic and scotopic conditions the pupil size increases, increasing the effects on visual performance of uncorrected (residual) refractive errors. The i.

Innate Immunity to : Evolving Paradigms in Soft Tissue and Invasive Infections.

causes a wide range of diseases that together embody a significant public health burden. Aided by metabolic flexibility and a large virulence repertoire, has the remarkable ability to hematogenously disseminate and infect various tissues, including skin, lung, heart, and bone, among others. The hallmark lesions of invasive staphylococcal infections, abscesses, simultaneously denote the powerful innate immune responses to tissue invasion as well as the ability of staphylococci to persist within these lesions.

Early TGF-β inhibition in mice reduces the incidence of breast cancer induced bone disease in a myeloid dependent manner.

The tumor-cell microenvironment is recognized as a dynamic place where critical cell interactions occur and play an important role in altering tumorigenesis. While many studies have investigated the effects of cellular cross-talk within distinct tumor microenvironments, these interactions have yet to be fully examined in bone. It is well-established that many common cancers metastasize to bone, resulting in the development of tumor-induced bone disease (TIBD), a multi-facetted illness that is driven by complex cell interactions within the bone marrow.

Evolution of T Cell Responses during Measles Virus Infection and RNA Clearance.

Measles is an acute viral disease associated both with immune suppression and development of life-long immunity. Clearance of measles virus (MeV) involves rapid elimination of infectious virus during the rash followed by slow elimination of viral RNA. To characterize cellular immune responses during recovery, we analyzed the appearance, specificity and function of MeV-specific T cells for 6 months after respiratory infection of rhesus macaques with wild type MeV.

The corneal nerve density in the sub-basal plexus decreases with increasing myopia: a pilot study.

Purpose: Myopia can cause many changes in the health of the eye. As it becomes more prevalent worldwide, more patients seek correction in the form of glasses, contact lenses and refractive surgery. In this study we explore the impact that high myopia has on central corneal nerve density by comparing sub basal nerve plexus density measured by confocal microscopy in a variety of refractive errors.

Monoclonal Antibodies Against the Staphylococcus aureus Bicomponent Leukotoxin AB Isolated Following Invasive Human Infection Reveal Diverse Binding and Modes of Action.

The 2-component leukotoxin LukAB is critical for Staphylococcus aureus targeting and killing of human neutrophils ex vivo and is produced in the setting of human infection. We report 3 LukAB-specific human monoclonal antibodies (mAbs) with distinct mechanisms of toxin neutralization and in vivo efficacy. Three hybridomas secreting mAbs with anti-LukAB activity (designated SA-13, -15, and -17) were generated from B cells obtained from a 12-year-old boy with S.

Repurposing the Nonsteroidal Anti-inflammatory Drug Diflunisal as an Osteoprotective, Antivirulence Therapy for Staphylococcus aureus Osteomyelitis.

Staphylococcus aureus osteomyelitis is a common and debilitating invasive infection of bone. Treatment of osteomyelitis is confounded by widespread antimicrobial resistance and the propensity of bacteria to trigger pathological changes in bone remodeling that limit antimicrobial penetration to the infectious focus. Adjunctive therapies that limit pathogen-induced bone destruction could therefore limit morbidity and enhance traditional antimicrobial therapies.

Bacterial Hypoxic Responses Revealed as Critical Determinants of the Host-Pathogen Outcome by TnSeq Analysis of Staphylococcus aureus Invasive Infection.

Staphylococcus aureus is capable of infecting nearly every organ in the human body. In order to infiltrate and thrive in such diverse host tissues, staphylococci must possess remarkable flexibility in both metabolic and virulence programs. To investigate the genetic requirements for bacterial survival during invasive infection, we performed a transposon sequencing (TnSeq) analysis of S.

Replication of many human viruses is refractory to inhibition by endogenous cellular microRNAs.

The issue of whether viruses are subject to restriction by endogenous microRNAs (miRNAs) and/or by virus-induced small interfering RNAs (siRNAs) in infected human somatic cells has been controversial. Here, we address this question in two ways. First, using deep sequencing, we demonstrate that infection of human cells by the RNA virus dengue virus (DENV) or West Nile virus (WNV) does not result in the production of any virus-derived siRNAs or viral miRNAs.

Modeling the foveal cone mosaic imaged with adaptive optics scanning laser ophthalmoscopy.

To better understand the limitations of high-resolution adaptive optics scanning laser ophthalmoscopy (AOSLO), we describe an imaging model that examines the smallest cone photoreceptors in the fovea of normal human subjects and analyze how different factors contribute to their resolution. The model includes basic optical factors such as wavelength and pupil size, and defines limits caused by source coherence which are specific to the AOSLO imaging modality as well as foveal cone structure. The details of the model, its implications for imaging, and potential techniques to circumvent the limitations are discussed in this paper.

The locus of fixation and the foveal cone mosaic.

High-resolution retinal imaging with adaptive optics was used to record the position of a light stimulus on the cone mosaic, with an error at least five times smaller than the diameter of the smallest foveal cones. We discuss the factors that limit the accuracy with which absolute retinal position can be determined. In five subjects, the standard deviation of fixation positions measured in discrete trials ranged from 2.