Comparison of specific in-vitro virulence gene expression and innate host response in locally invasive vs colonizer strains of Streptococcus pneumoniae.

Among Rochester NY children, a dramatic increase in nasopharyngeal (NP) colonization by non-vaccine pneumococcal serotypes 35B and 15A occurred during years 2010-2015, after introduction of 13-valent pneumococcal conjugate vaccine (PCV13). In our population, serotype 35B strains colonized in the nasopharynx (NP) but infrequently caused acute otitis media (AOM) whereas serotype 15A strains displayed virulence, evidenced by causing AOM. To explain the virulence difference, virulence genes expression between 35B and 15A, as well as the host's immune response during asymptomatic colonization were analyzed.

Changes in lung immune cell infiltrates after electric field treatment in mice.

Exogenous electric fields are currently used in human therapy in a number of contexts. Interestingly, electric fields have also been shown to alter migration and function of immune cells, suggesting the potential for electric field-based immune therapy. Little is known as to the effect of electric field treatment (EFT) on the lung.

Nasopharyngeal colonization with pathobionts is associated with susceptibility to respiratory illnesses in young children.

Some children are more susceptible to viral and bacterial respiratory infections in the first few years of life than others. However, the factors contributing to this susceptibility are incompletely understood. In a retrospective analysis of clinical samples collected from a prospectively-enrolled cohort of 358 children we sought associations between physician-attended illness visits and bacterial colonization in the first five years of life.

Ampicillin triggers the release of Pal in toxic vesicles from Escherichia coli.

In addition to lipopolysaccharides (LPS), outer membrane proteins - Lpp, OmpA and peptidoglycan-associated lipoprotein (Pal) - are part of the outer membrane of Escherichia coli and are proposed to contribute to bacterial sepsis-related inflammation. This study showed that ampicillin (a β-lactam antibiotic) enhances Pal's release from Escherichia coli to a greater extent than gentamicin and levofloxacin (aminoglycoside and quinolone antibiotics, respectively). It is proposed that the majority of Pal is released in outer membrane vesicles (OMVs), which also contain LPS and other outer membrane and periplasmic proteins.

Comparison of anti-capsular antibody quantity and functionality in children after different primary dose and booster schedules of 13 valent-pneumococcal conjugate vaccine.

Different schedules for pediatric use of the 13-valent pneumococcal conjugate vaccine (PCV-13) are recommended in different countries and the U.S. Advisory Committee on Immunization Practices (ACIP) has considered potential of changing from 3 primary doses plus a booster (3p + 1) to two primary doses plus a booster (2p + 1) for protection against Streptococcus pneumoniae.

Comparison of pneumococcal conjugate vaccine (PCV-13) cellular immune responses after primary and booster doses of vaccine.

Since their widespread use, pneumococcal conjugate vaccines (PCVs) have proven effective at reducing both invasive and noninvasive pneumococcal diseases and nasopharyngeal carriage of (). To establish this level of protection, a three-dose schedule with a single booster (3 + 1) was the immunization regime in the USA. Alternatively, WHO-approved schedules of 3 + 0 and 2 + 1 are now becoming adopted in many countries to reduce the cost of vaccination.

Immunologic dysfunction contributes to the otitis prone condition.

Acute Otitis Media (AOM) is a multifactorial disease occurring mostly in young children who are immunologically naïve to AOM pathogens. This review focuses on work from Rochester NY, USA over the past 12 years among young children who had AOM infections microbiologically-confirmed by tympanocentesis, so called "stringently-defined". Among stringently-defined otitis prone children deficiencies in fundamental immune defense mechanisms have been identified that contribute to the propensity of young children to experience recurrent AOM.

Towards a Treatment for Gulf War Illness: A Consensus Docking Approach.

Introduction: Gulf War Illness (GWI) currently has no known cure and affects soldiers deployed during the Persian Gulf War. It is thought to originate from exposure to neurotoxicants combined with battlefield stress, and previous research indicates that treatment first involves inhibition of interleukin-2 and tumor necrosis factor alpha, followed by the glucocorticoid receptor. However, the off-target effects of pharmaceuticals hinder development of a drug treatment therapy.

Rising Pneumococcal Antibiotic Resistance in the Post-13-Valent Pneumococcal Conjugate Vaccine Era in Pediatric Isolates From a Primary Care Setting.

Background: Antibiotic-resistant Streptococcus pneumoniae strains may cause infections that fail to respond to antimicrobial therapy. Results reported from hospitalized patients with invasive, bacteremic infections may not be the same as those observed in a primary care setting where young children receive care for noninvasive infections. Young children experience the highest burden of pneumococcal disease.

Panel 3: Genomics, precision medicine and targeted therapies.

Objective: To review the most recent advances in human and bacterial genomics as applied to pathogenesis and clinical management of otitis media.

Data Sources: PubMed articles published since the last meeting in June 2015 up to June 2019.

Review Methods: A panel of experts in human and bacterial genomics of otitis media was formed.

Comparative Analysis of Microbiome in Nasopharynx and Middle Ear in Young Children With Acute Otitis Media.

Acute otitis media (AOM) is the most common pediatric infection for which antibiotics are prescribed in the United States. The role of the respiratory tract microbiome in pathogenesis and immune modulation of AOM remains unexplored. We sought to compare the nasopharyngeal (NP) microbiome of children 1 to 3 weeks prior to onset of AOM vs.

Statistical projection of post-vaccination antibody kinetics between dosing schedules.

Determining a recommended dosage schedule is a crucial component of vaccine administration, and is often subject to reassessment. Ideally, recommendations will be supported by multiple arm clinical trials. However, the considerable cost in both resources and time means that a method of predicting post-vaccine humoral antibody levels associated with a hypothetical schedule using data collected from a currently implemented schedule would be of significant benefit to vaccination practice.

Astrocyte-specific transcriptome analysis using the ALDH1L1 bacTRAP mouse reveals novel biomarkers of astrogliosis in response to neurotoxicity.

Neurotoxicology is hampered by the inability to predict regional and cellular targets of toxicant-induced damage. Evaluating astrogliosis overcomes this problem because reactive astrocytes highlight the location of toxicant-induced damage. While enhanced expression of glial fibrillary acidic protein is a hallmark of astrogliosis, few other biomarkers have been identified.

Computation of Robust Minimal Intervention Sets in Multi-Valued Biological Regulatory Networks.

Enabled by rapid advances in computational sciences, logical modeling of complex and large biological networks is more and more feasible making it an increasingly popular approach among biologists. Automated high-throughput, drug target identification is one of the primary goals of this network biology. Targets identified in this way are then used to mine a library of drug chemical compounds in order to identify appropriate therapies.

Genetically detoxified pertussis toxin induces superior antigen specific CD4 T cell responses compared to chemically detoxified pertussis toxin.

Pertussis is resurgent worldwide. Currently available acellular pertussis vaccines contain chemically detoxified pertussis toxin (PTc); a highly immunogenic genetically detoxified pertussis toxin (PTg) vaccine has been off the market for over a decade. We compared CD4 T cell and B cell responses induced by genetically detoxified pertussis toxin (PTg) and chemically detoxified pertussis toxin (PTc) using naive human neonatal cells.

Anti-EF-Tu IgG titers increase with age and may contribute to protection against the respiratory pathogen Haemophilus influenzae.

Non-typeable Haemophilus influenzae (NTHi) is a pathogen that commonly colonizes the nasopharynx of preschool children, causing opportunistic infections including acute otitis media (AOM). Patients suffering from chronic obstructive pulmonary disease (COPD) are persistently colonized with NTHi and occasionally suffer from exacerbations by the bacterium leading to increased morbidity. Elongation-factor thermo unstable (EF-Tu), a protein critical for bacterial protein synthesis, has been found to moonlight on the surface of several bacteria.

Using a Consensus Docking Approach to Predict Adverse Drug Reactions in Combination Drug Therapies for Gulf War Illness.

Gulf War Illness (GWI) is a chronic multisymptom illness characterized by fatigue, musculoskeletal pain, and gastrointestinal and cognitive dysfunction believed to stem from chemical exposures during the 1990⁻1991 Persian Gulf War. There are currently no treatments; however, previous studies have predicted a putative multi-intervention treatment composed of inhibiting Th1 immune cytokines followed by inhibition of the glucocorticoid receptor (GCR) to treat GWI. These predictions suggest the use of specific monoclonal antibodies or suramin to target interleukin-2 and tumor necrosis factor α , followed by mifepristone to inhibit the GCR.

Impaired Proinflammatory Response in Stringently Defined Otitis-prone Children During Viral Upper Respiratory Infections.

Background: Viral upper respiratory infections (URIs) are common and often precipitate acute otitis media (AOM), caused by bacterial otopathogens, in young children. Acute inflammatory responses initiated in the early phase of viral URI contribute to preventing the development of AOM. Stringently-defined otitis-prone (sOP) children are susceptible to recurrent AOM.

Effectiveness of 13-valent pneumococcal conjugate vaccination for protection against acute otitis media caused by Streptococcus pneumoniae in healthy young children: a prospective observational study.

Background: With wide use of the seven-valent pneumococcal conjugate vaccine (PCV7) for protection against acute otitis media caused by Streptococcus pneumoniae serotypes included in the vaccine, efficacy testing for the 13-valent vaccine (PCV13) was not feasible. We aimed to assess the effectiveness of PCV13 in preventing acute otitis media caused by the six serotypes in PCV13 that were not in PCV7.

Methods: We did a longitudinal observational study in healthy children seen as outpatients in a private paediatric practice in Rochester, NY, USA.

Psychoneuroimmunology and Natural Killer Cells: The Chromium-Release Whole-Blood Assay.

Natural killer (NK) cells are an essential component of innate immunity. These lymphocytes are also sensitive barometers of the effects of endogenous and exogenous stressors on the immune system. This chapter describes a chromium (Cr)-release bioassay designed to measure to the target cell killing capacity of NK cells (NKCC).

Breaking Away: The Role of Homeostatic Drive in Perpetuating Depression.

We propose that the complexity of regulatory interactions modulating brain neurochemistry and behavior is such that multiple stable responses may be supported, and that some of these alternate regulatory programs may play a role in perpetuating persistent psychological dysfunction. To explore this, we constructed a model network representing major neurotransmission and behavioral mechanisms reported in literature as discrete logic circuits. Connectivity and information flow through this biobehavioral circuitry supported two distinct and stable regulatory programs.

Exploring the Diagnostic Potential of Immune Biomarker Co-expression in Gulf War Illness.

Complex disorders like Gulf War illness (GWI) often defy diagnosis on the basis of a single biomarker and may only be distinguishable by considering the co-expression of multiple markers measured in response to a challenge. We demonstrate the practical application of such an approach using an example where blood was collected from 26 GWI, 13 healthy control subjects, and 9 unhealthy controls with chronic fatigue at three points during a graded exercise challenge. A 3-way multivariate projection model based on 12 markers of endocrine and immune function was constructed using a training set of n = 10 GWI and n = 11 healthy controls.

Increasing Resilience to Traumatic Stress: Understanding the Protective Role of Well-Being.

The brain maintains homeostasis in part through a network of feedback and feed-forward mechanisms, where neurochemicals and immune markers act as mediators. Using a previously constructed model of biobehavioral feedback, we found that in addition to healthy equilibrium another stable regulatory program supported chronic depression and anxiety. Exploring mechanisms that might underlie the contributions of subjective well-being to improved therapeutic outcomes in depression, we iteratively screened 288 candidate feedback patterns linking well-being to molecular signaling networks for those that maintained the original homeostatic regimes.