Protection against induced by OMV-based Meningococcal Vaccines are associated with cross-species directed humoral and cellular immune responses.

Limited protective immunologic responses to natural infection and a lack of knowledge about mechanisms of protection have hampered development of an effective vaccine. Recent studies in humans and mice have found meningococcal outer membrane vesicle-containing vaccines (OMV) induce cross species immune responses against gonococci and are associated with protection. The exact mechanisms or how humoral and cellular immunity are related to protection, remain unclear.

Update on syphilis diagnostics.

Purpose Of Review: Syphilis is rising globally, with resultant increases in morbidity and mortality that disproportionately impact underserved populations. Appropriate screening and testing for syphilis with accurate, reliable, affordable, and timely assays is crucial for combating this epidemic. This review provides a brief overview of laboratory methods for syphilis diagnosis, with a focus on recent updates in diagnostics and directions for future research.

Hepatovirus translation requires PDGFA-associated protein 1, an eIF4E-binding protein regulating endoplasmic reticulum stress responses.

The overexpression and misfolding of viral proteins in the endoplasmic reticulum (ER) may cause cellular stress, thereby inducing a cytoprotective, proteostatic host response involving phosphorylation of eukaryotic translation initiation factor 2 subunit alpha (eIF2α). Here, we show that hepatitis A virus, a positive-strand RNA virus responsible for infectious hepatitis, adopts a stress-resistant, eIF2α-independent mechanism of translation to ensure the synthesis of viral proteins within the infected liver. Cap-independent translation directed by the hepatovirus internal ribosome entry site and productive hepatovirus infection of mice both require platelet-derived growth factor subunit A (PDGFA)-associated protein 1 (PDAP1), a small phosphoprotein of unknown function with eIF4E-binding activity.

Evolution of Postpandemic Nurse Orientation Through an Academic-Practice Partnership.

An academic-practice partnership engaged in redesigning the postpandemic orientation process for newly hired nurses in a large academic health system. Results from needs assessments and collaboration efforts informed the orientation program redesign, and the National Implementation Research Network framework guided project development. The orientation redesign aimed to enhance efficiency, readiness for unit-specific orientation, and stakeholder satisfaction.

Promising developments in gonococcal vaccines.

Purpose Of Review: While effective vaccines to prevent invasive infections by Neisseria meningitidis have been deployed around the world, development of a vaccine to prevent Neisseria gonorrhoeae has lagged. After multiple failed vaccine candidates, vaccine development for N. gonorrhoeae is showing promise for the first time in several decades.

MtrCDE Efflux Pump During Experimental Genital Tract Infection in Men and Mice Reveals the Presence of Within-Host Colonization Bottleneck.

Unlabelled: The MtrCDE efflux pump of exports a wide range of antimicrobial compounds that the gonococcus encounters at mucosal surfaces during colonization and infection. Here, we evaluate the role of this efflux pump system in strain FA1090 in human male urethral infection with a Controlled Human Infection Model. Using the strategy of competitive multi-strain infection with wild-type FA1090 and an isogenic mutant strain that does not contain a functional MtrCDE pump, we found that the presence of the efflux pump during human experimental infection did not confer a competitive advantage.

Interferon regulatory factor 3 mediates effective antiviral responses to human coronavirus 229E and OC43 infection.

Interferon regulatory factors (IRFs) are key elements of antiviral innate responses that regulate the transcription of interferons (IFNs) and IFN-stimulated genes (ISGs). While the sensitivity of human coronaviruses to IFNs has been characterized, antiviral roles of IRFs during human coronavirus infection are not fully understood. Type I or II IFN treatment protected MRC5 cells from human coronavirus 229E infection, but not OC43.

Commensal Neisseria species share immune suppressive mechanisms with Neisseria gonorrhoeae.

Neisseria gonorrhoeae is a highly adapted human sexually transmitted pathogen that can cause symptomatic infections associated with localized inflammation as well as asymptomatic and subclinical infections, particularly in females. Gonococcal infection in humans does not generate an effective immune response in most cases, which contributes to both transmission of the pathogen and reinfection after treatment. Neisseria gonorrhoeae is known to evade and suppress human immune responses through a variety of mechanisms.

The role of the genital microbiota in the acquisition and pathogenesis of sexually transmitted infections.

Purpose Of Review: There are an estimated 374 million new sexually transmitted infections (STIs) worldwide every year. Our review article examines the current evidence of how STI acquisition, transmission, and pathogenesis is impacted upon by the genital microbiota, with a focus on epidemiological, biochemical, and immunological features.

Recent Findings: At least in women, a genital microbiota dominated by lactobacilli has long been considered optimal for reproductive health, while depletion of lactobacilli may lead to a genital microenvironment dominated by anaerobic pathogens, which can manifest clinically as bacterial vaginosis.

Nonlytic cellular release of hepatitis A virus requires dual capsid recruitment of the ESCRT-associated Bro1 domain proteins HD-PTP and ALIX.

Although picornaviruses are conventionally considered 'nonenveloped', members of multiple picornaviral genera are released nonlytically from infected cells in extracellular vesicles. The mechanisms underlying this process are poorly understood. Here, we describe interactions of the hepatitis A virus (HAV) capsid with components of host endosomal sorting complexes required for transport (ESCRT) that play an essential role in release.

Experimental Urethral Infection with Neisseria gonorrhoeae.

Gonorrhea rates and antibiotic resistance are both increasing. Neisseria gonorrhoeae (Ng) is an exclusively human pathogen and is exquisitely adapted to its natural host. Ng can subvert immune responses and undergoes frequent antigenic variation, resulting in limited immunity and protection from reinfection.

Cervicovaginal Microbiota Predicts Clinical Presentation.

infection of the female lower genital tract can present with a spectrum of phenotypes ranging from asymptomatic carriage to symptomatic cervical inflammation, or cervicitis. The factors that contribute to the development of asymptomatic or symptomatic infections are largely uncharacterized. We conducted a pilot study to assess differences in the cervicovaginal microbial community of patients presenting with symptomatic vs.

Effectiveness of a patient-centred sleep study report in the management of obstructive sleep apnoea.

Purpose: Obstructive sleep apnoea (OSA) is a common condition with a range of short- and long-term health implications. Providing patient-centred care is a key principle to ensure patients are well informed and empowered to participate in clinical decision making. This study aimed to develop a patient-centred sleep study report for patients with obstructive sleep apnoea and to determine whether or not its implementation led to improved patient understanding of their disease.

Demonstration of Equivalence of Generic Glatiramer Acetate and Copaxone.

The objective of the current work was to demonstrate the equivalence of Mylan's glatiramer acetate (GA) to that of the reference product Copaxone (COP) using the four criteria for active pharmaceutical ingredient sameness as established by the US Food and Drug Administration (FDA). The reaction scheme used to produce Mylan's glatiramer acetate (MGA) was compared with that of COP, determined from publicly available literature. Comparative analyses of MGA and COP were performed for physicochemical properties such as amino acid composition and molecular weight distributions.

Nonviral sexually transmitted infections in pregnancy: current controversies and new challenges.

Purpose Of Review: This review provides an update of nonviral, curable sexually transmitted infections (STIs) in pregnancy and summarizes our understanding of the current issues and controversies surrounding risk factors, screening, and treatment of STIs in pregnancy primarily in high-income countries (using the United States and the United Kingdom as examples). The infections covered in this review are syphilis, gonorrhea, chlamydia, trichomoniasis, and Mycoplasma genitalium infections.

Recent Findings: Overall, limited modern data is available to update researchers and clinicians on the epidemiology and care of STIs in pregnancy.

The serogroup B meningococcal outer membrane vesicle-based vaccine 4CMenB induces cross-species protection against Neisseria gonorrhoeae.

There is a pressing need for a gonorrhea vaccine due to the high disease burden associated with gonococcal infections globally and the rapid evolution of antibiotic resistance in Neisseria gonorrhoeae (Ng). Current gonorrhea vaccine research is in the stages of antigen discovery and the identification of protective immune responses, and no vaccine has been tested in clinical trials in over 30 years. Recently, however, it was reported in a retrospective case-control study that vaccination of humans with a serogroup B Neisseria meningitidis (Nm) outer membrane vesicle (OMV) vaccine (MeNZB) was associated with reduced rates of gonorrhea.

Time-based pulmonary features from electrical impedance tomography demonstrate ventilation heterogeneity in chronic obstructive pulmonary disease.

Pulmonary electrical impedance tomography (EIT) is a functional imaging technique that allows real-time monitoring of ventilation distribution. Ventilation heterogeneity (VH) is a characteristic feature of chronic obstructive pulmonary disease (COPD) and has previously been quantified using features derived from tidal variations in the amplitude of the EIT signal. However, VH may be better described by time-based metrics, the measurement of which is made possible by the high temporal resolution of EIT.

Commensal Neisseria Kill Neisseria gonorrhoeae through a DNA-Dependent Mechanism.

The mucosa is colonized with commensal Neisseria. Some of these niches are sites of infection for the STD pathogen Neisseria gonorrhoeae (Ngo). Given the antagonistic behavior of commensal bacteria toward their pathogenic relatives, we hypothesized that commensal Neisseria may negatively affect Ngo colonization.

Experimental Human Infection with Neisseria gonorrhoeae.

Experimental infection of male volunteers with Neisseria gonorrhoeae is safe and reproduces the clinical features of naturally acquired gonococcal urethritis. The human model is useful for testing the importance of putative gonococcal virulence factors for urethral infection in men and the model presents opportunities to examine host immune responses that may be exploited or improved in development and testing of gonococcal vaccines. In this chapter, we describe methods for production, characterization, and storage of N.

Viral DNA Binding to NLRC3, an Inhibitory Nucleic Acid Sensor, Unleashes STING, a Cyclic Dinucleotide Receptor that Activates Type I Interferon.

Immune suppression is a crucial component of immunoregulation and a subgroup of nucleotide-binding domain (NBD), leucine-rich repeat (LRR)-containing proteins (NLRs) attenuate innate immunity. How this inhibitory function is controlled is unknown. A key question is whether microbial ligands can regulate this inhibition.

Human Immune Responses and the Natural History of Infection.

The intimate relationship between humans and infections span centuries, which is evidenced in case reports from studies dating back to the late 1700s and historical references that predate medical literature. is an exclusive human pathogen that infects the genital tract of both men and women as well as other mucosal surfaces including the oropharynx and rectum. In symptomatic infections, induces a robust inflammatory response at the site of infection.

Respiratory system reactance reflects communicating lung volume in chronic obstructive pulmonary disease.

Respiratory system reactance (Xrs) measured by the forced oscillation technique (FOT) is theoretically and experimentally related to lung volume. In chronic obstructive pulmonary disease (COPD), the absolute volume measured by body plethysmography includes a proportion that is inaccessible to pressure oscillations applied via the mouth, that is, a "noncommunicating" lung volume. We hypothesized that in COPD the presence of noncommunicating lung would disrupt the expected Xrs-volume relationship compared with plethysmographic functional residual capacity (FRC).

RIG-I Detects Kaposi's Sarcoma-Associated Herpesvirus Transcripts in a RNA Polymerase III-Independent Manner.

Retinoic acid-inducible gene I (RIG-I) is a cytosolic pathogen recognition receptor that initiates the innate immune response against many RNA viruses. We previously showed that RIG-I restricts Kaposi's sarcoma-associated herpesvirus (KSHV) reactivation (J. A.

Properly folded and functional PorB from inhibits dendritic cell stimulation of CD4 T cell proliferation.

is an exclusive human pathogen that evades the host immune system through multiple mechanisms. We have shown that suppresses the capacity of antigen-presenting cells to induce CD4 T cell proliferation. In this study, we sought to determine the gonococcal factors involved in this adaptive immune suppression.