Substance Use Screening in a Large Pediatric Primary Care Network: A Quality Improvement Project.

Background: This project aimed to introduce substance use screening, using the CRAFFT (Car, Relax, Alone, Forget, Family/Friends, Trouble) screening tool, into the routine care of adolescents using quality improvement strategies and tools.

Methods: We expanded a single-site project showing the successful introduction of CRAFFT screening into adolescent care to include the entire 34-site primary care network of a children's hospital in Northeastern Ohio. We deployed quality improvement methodology to facilitate the acceptance and use of the screener.

Genotypic diversity, virulence, and molecular genetic tools in .

Histoplasmosis is arguably the most common fungal respiratory infection worldwide, with hundreds of thousands of new infections occurring annually in the United States alone. The infection can progress in the lung or disseminate to visceral organs and can be difficult to treat with antifungal drugs. , the causative agent of the disease, is a pathogenic fungus that causes life-threatening lung infections and is globally distributed.

Phenotypic characterization of cryptic species in the fungal pathogen .

Histoplasmosis is an endemic mycosis that often presents as a respiratory infection in immunocompromised patients. Hundreds of thousands of new infections are reported annually around the world. The etiological agent of the disease, is a dimorphic fungus commonly found in the soil where it grows as mycelia.

Phenotypic characterization of cryptic species in the fungal pathogen .

Histoplasmosis is an endemic mycosis that often presents as a respiratory infection in immunocompromised patients. Hundreds of thousands of new infections are reported annually around the world. The etiological agent of the disease, , is a dimorphic fungus commonly found in the soil where it grows as mycelia.

Methotrexate suppresses psoriatic skin inflammation by inhibiting muropeptide transporter SLC46A2 activity.

Cytosolic innate immune sensing is critical for protecting barrier tissues. NOD1 and NOD2 are cytosolic sensors of small peptidoglycan fragments (muropeptides) derived from the bacterial cell wall. These muropeptides enter cells, especially epithelial cells, through unclear mechanisms.

Chromosome-Level Genome Assembly of a Human Fungal Pathogen Reveals Synteny among Geographically Distinct Species.

Histoplasma capsulatum, a dimorphic fungal pathogen, is the most common cause of fungal respiratory infections in immunocompetent hosts. is endemic in the Ohio and Mississippi River Valleys in the United States and is also distributed worldwide. Previous studies have revealed at least eight clades, each specific to a geographic location: North American classes 1 and 2 (NAm 1 and NAm 2), Latin American groups A and B (LAm A and LAm B), Eurasian, Netherlands, Australian and African, and an additional distinct lineage (H81) comprised of Panamanian isolates.

Predicted Functional and Structural Diversity of Receiver Domains in Fungal Two-Component Regulatory Systems.

Fungal two-component regulatory systems incorporate receiver domains into hybrid histidine kinases (HHKs) and response regulators. We constructed a nonredundant database of 670 fungal receiver domain sequences from 51 species sampled from nine fungal phyla. A much greater proportion (21%) of predicted fungal response regulators did not belong to known groups than previously appreciated.

Evaluating the impact of prescription isodose line on plan quality using Gamma Knife inverse planning.

The impact of selection of prescription isodose line (IDL) on plan quality has not been well evaluated during inverse planning (IP). In this study, a total of 180 IP plans at five levels of IDL were generated for 30 brain metastases (BMs). For each BM, one round of IP was performed with typical IP settings, followed by a quick fine-tuning to ensure the same target coverage and comparable conformality index.

A Radical Reimagining of Fungal Two-Component Regulatory Systems.

Bacterial two-component regulatory systems (TCSs) mediate signal transduction by transferring phosphoryl groups between sensor kinase and response regulator proteins, sometimes using intermediary histidine-phosphotransferase (Hpt) domains to form multistep phosphorelays. Because (i) almost all known fungal sensor kinases exhibit a domain architecture characteristic of bacterial TCS phosphorelays, (ii) all known fungal Hpts are stand-alone proteins suited to shuttle between cytoplasm and nucleus, and (iii) the best-characterized fungal TCS is a canonical phosphorelay, it is widely assumed that most or all fungal TCSs function via phosphorelays. However, fungi generally encode more sensor kinases than Hpts or response regulators, leading to a disparity between putative phosphorelay inputs and outputs.

Activity of Tracheal Cytotoxin of in a Human Tracheobronchial 3D Tissue Model.

is a highly contagious pathogen which causes whooping cough in humans. A major pathophysiology of infection is the extrusion of ciliated cells and subsequent disruption of the respiratory mucosa. Tracheal cytotoxin (TCT) is the only virulence factor produced by that has been able to recapitulate this pathology in animal models.

The Yersinia pestis GTPase BipA Promotes Pathogenesis of Primary Pneumonic Plague.

is a highly virulent pathogen and the causative agent of bubonic, septicemic, and pneumonic plague. Primary pneumonic plague caused by inhalation of respiratory droplets contaminated with is nearly 100% lethal within 4 to 7 days without antibiotic intervention. Pneumonic plague progresses in two phases, beginning with extensive bacterial replication in the lung with minimal host responsiveness, followed by the abrupt onset of a lethal proinflammatory response.

Biodiverse Species Elicit Distinct Patterns of Pulmonary Inflammation following Sublethal Infection.

is an endemic dimorphic fungus that can cause disease in healthy and immunocompromised individuals after the transition of inhaled spores into the facultative intracellular yeast form. There is substantial diversity among species, but it is not clear how this heterogeneity impacts the progression of pathology and cellular immune responses during acute respiratory infection, which represents the vast majority of histoplasmosis disease burden. After inoculating mice intranasally with a sublethal inoculum, we characterized the immune response to (strain G186A) and (strain G217B) using comprehensive flow cytometric and single-cell analyses.

Tn-Seq Analysis Identifies Genes Important for Yersinia pestis Adherence during Primary Pneumonic Plague.

Following inhalation, rapidly colonizes the lung to establish infection during primary pneumonic plague. Although several adhesins have been identified in spp., the factors mediating early adherence in the lung remain unknown.

Dosimetric comparison of inverse and forward planning for Gamma Knife stereotactic radiosurgery of brain metastases.

The Leksell GammaPlan (LGP) with an inverse planning (IP) tool has been upgraded to version 11.1 since its launch in 2010. We evaluated its IP planning performance by re-planning 16 targets that had been planned using forward planning (FP).

Interactions of Symbiotic Partners Drive the Development of a Complex Biogeography in the Squid-Vibrio Symbiosis.

Microbes live in complex microniches within host tissues, but how symbiotic partners communicate to create such niches during development remains largely unexplored. Using confocal microscopy and symbiont genetics, we characterized the shaping of host microenvironments during light organ colonization of the squid by the bacterium During embryogenesis, three pairs of invaginations form sequentially on the organ's surface, producing pores that lead to interior compressed tubules at different stages of development. After hatching, these areas expand, allowing cells to enter and migrate ∼120 μm through three anatomically distinct regions before reaching blind-ended crypt spaces.

Inhibition of Neutrophil Primary Granule Release during Yersinia pestis Pulmonary Infection.

Inhalation of causes primary pneumonic plague, the most severe manifestation of plague that is characterized by a dramatic neutrophil influx to the lungs. Neutrophils are ineffective during primary pneumonic plague, failing to control growth in the airways. However, the mechanisms by which resists neutrophil killing are incompletely understood.

Human Neutrophil Isolation and Degranulation Responses to Yersinia pestis Infection.

Neutrophils are the primary immune cell recruited to the site of bacterial infection, where they can rapidly deploy vesicles filled with various pro-inflammatory and anti-microbial proteins. This degranulation process, combined with oxidative and nitrosative mechanisms, is a major part of the initial host response to kill microorganisms. Neutrophils are one of the main cell types that interact with Yersinia pestis during infection, which is often lethal in the absence of prompt antibiotic treatment.

Peptidoglycan Recognition Protein 4 Suppresses Early Inflammatory Responses to and Contributes to Sphingosine-1-Phosphate Receptor Agonist-Mediated Disease Attenuation.

Incidence of whooping cough (pertussis), a bacterial infection of the respiratory tract caused by the bacterium , has reached levels not seen since the 1950s. Antibiotics fail to improve the course of disease unless administered early in infection. Therefore, there is an urgent need for the development of antipertussis therapeutics.

Improved Dose Conformity for Adjacent Targets: A Novel Planning Technique for Gamma Knife Stereotactic Radiosurgery.

Purpose In the current Gamma Knife (GK) planning system (GammaPlan, version 10.2, Elekta AB, Stockholm, Sweden), multiple adjacent brain metastasis (BMs) had to be planned sequentially if BMs were drawn separately, leading to less conformal target dose in the composite plan due to inter-target dose contribution and fine-tuning of the shots being quite tedious. We proposed a method to improve target dose conformality and planning efficiency for such cases.

Recent admixture between species of the fungal pathogen .

Hybridization between species of pathogens has the potential to speed evolution of virulence by providing the raw material for adaptation through introgression or by assembling new combinations of virulence traits. Fungal diseases are a source high morbidity, and remain difficult to treat. Yet the frequency of hybridization between fungal species has rarely been explored, and the functional role of introgressed alleles remains largely unknown.

Dehydration triggers ecdysone-mediated recognition-protein priming and elevated anti-bacterial immune responses in Drosophila Malpighian tubule renal cells.

Background: Drosophila is a powerful model for the study of factors modulating innate immunity. This study examines the effect of water-loss dehydration on innate immune responsiveness in the Drosophila renal system (Malpighian tubules; MTs), and how this leads to elevated host defense and contributes to immunosenescence.

Results: A short period of desiccation-elevated peptidoglycan recognition protein-LC (PGRP-LC) expression in MTs, increased antimicrobial peptide (AMP) gene induction, and protected animals from bacterial infection.

Prevalence of trachoma in the Kayes region of Mali eight years after stopping mass drug administration.

Background: In 2009, three years after stopping mass treatment with azithromycin, a trachoma impact survey in four health districts in the Kayes region of Mali found a prevalence of trachomatous inflammation-follicular (TF) among children aged 1 to 9 years of >5% and a trachomatous trichiasis (TT) prevalence within the general population (≥1-year-old) of <1%. As a result, the government's national trachoma program expanded trichiasis surgery and related activities required to achieve trachoma elimination.

Methodology/principal Findings: In 2015, to assess progress towards elimination, a follow-up impact survey was conducted in the Kayes, Kéniéba, Nioro and Yélimané health districts.