[Patient-oriented optimization of the quality of care in a specialized outpatient clinic in a tertiary rheumatology center : A qualitative study].

Background: The adaptation of structures and processes in treatment procedures can contribute to increasing patient satisfaction and is the focus of patient-oriented quality assurance.

Objective: To identify patient satisfaction as well as needs, expectations and preferences with respect to care and, based on this, to formulate recommendations for action to optimize the quality of care at a large tertiary rheumatology center.

Material And Methods: As part of a qualitative research approach, semi-structured patient interviews and a focus group interview consisting of physicians in rheumatology training in outpatient specialist care were conducted.

Bacterial Sphingolipids Exacerbate Colitis by Inhibiting ILC3-derived IL-22 Production.

Background & Aims: Gut bacterial sphingolipids, primarily produced by Bacteroidetes, have dual roles as bacterial virulence factors and regulators of the host mucosal immune system, including regulatory T cells and invariant natural killer T cells. Patients with inflammatory bowel disease display altered sphingolipids profiles in fecal samples. However, how bacterial sphingolipids modulate mucosal homeostasis and regulate intestinal inflammation remains unclear.

Interplay between human STING genotype and bacterial NADase activity regulates inter-individual disease variability.

Variability in disease severity caused by a microbial pathogen is impacted by each infection representing a unique combination of host and pathogen genomes. Here, we show that the outcome of invasive Streptococcus pyogenes infection is regulated by an interplay between human STING genotype and bacterial NADase activity. S.

Streptococcus pyogenes can support or inhibit growth of Haemophilus influenzae by supplying or restricting extracellular NAD.

Nicotinamide adenine dinucleotide (NAD+) is an essential co-factor for cellular metabolism and serves as a substrate in enzymatic processes. NAD+ is produced by de novo synthesis or salvage pathways in nearly all bacterial species. Haemophilus influenzae lacks the capacity for de novo synthesis, so it is dependent on import of NAD+ from the external environment or salvage biosynthetic pathways for recycling of NAD+ precursors and breakdown products.

Simultaneous Late, Late-Onset Group B Streptococcal Meningitis in Identical Twins.

To our knowledge, late, late-onset group B streptococcal (GBS) meningitis in identical twins has yet to be reported. We describe a case of 14-week-old twins who developed fever hours apart and presented simultaneously to the emergency department 2 days later with seizures. Blood and cerebrospinal fluid (CSF) cultures from both infants were positive for GBS.

Structure of the Streptococcus pyogenes NAD Glycohydrolase Translocation Domain and Its Essential Role in Toxin Binding to Oropharyngeal Keratinocytes.

The emergence and continued dominance of a Streptococcus pyogenes (group A Streptococcus, GAS) M1T1 clonal group is temporally correlated with acquisition of genomic sequences that confer high level expression of cotoxins streptolysin O (SLO) and NAD-glycohydrolase (NADase). Experimental infection models have provided evidence that both toxins are important contributors to GAS virulence. SLO is a cholesterol-dependent pore-forming toxin capable of lysing virtually all types of mammalian cells.

Identification of Group A Streptococcus Genes Directly Regulated by CsrRS and Novel Intermediate Regulators.

Adaptation of group A Streptococcus (GAS) to its human host is mediated by two-component systems that transduce external stimuli to regulate bacterial physiology. Among such systems, CsrRS (also known as CovRS) is the most extensively characterized for its role in regulating ∼10% of the GAS genome, including several virulence genes. Here, we show that extracellular magnesium and the human antimicrobial peptide LL-37 have opposing effects on the phosphorylation of the response regulator CsrR by the receptor kinase CsrS.

Improved transformation efficiency of group A Streptococcus by inactivation of a type I restriction modification system.

Streptococcus pyogenes or group A Streptococcus (GAS) is a leading cause of bacterial pharyngitis, skin and soft tissue infections, life-threatening invasive infections, and the post-infectious autoimmune syndromes of acute rheumatic fever and post-streptococcal glomerulonephritis. Genetic manipulation of this important pathogen is complicated by resistance of the organism to genetic transformation. Very low transformation efficiency is attributed to recognition and degradation of introduced foreign DNA by a type I restriction-modification system encoded by the hsdRSM locus.

RocA Binds CsrS To Modulate CsrRS-Mediated Gene Regulation in Group A .

The orphan regulator RocA plays a critical role in the colonization and pathogenesis of the obligate human pathogen group A Despite multiple lines of evidence supporting a role for RocA as an auxiliary regulator of the control of virulence two-component regulatory system CsrRS (or CovRS), the mechanism of action of RocA remains unknown. Using a combination of and techniques, we now find that RocA interacts with CsrS in the streptococcal membrane via its N-terminal region, which contains seven transmembrane domains. This interaction is essential for RocA-mediated regulation of CsrRS function.

Streptolysin O Induces the Ubiquitination and Degradation of Pro-IL-1β.

Group A Streptococcus (GAS) is a common and versatile human pathogen causing a variety of diseases. One of the many virulence factors of GAS is the secreted pore-forming cytotoxin streptolysin O (SLO), which has been ascribed multiple properties, including inflammasome activation leading to release of the potent inflammatory cytokine IL-1β from infected macrophages. IL-1β is synthesized as an inactive pro-form, which is activated intracellularly through proteolytic cleavage.

Capsular Polysaccharide of Group A .

Most clinical isolates of elaborate a capsular polysaccharide, which is composed of hyaluronic acid, a high-molecular-mass polymer of alternating residues of -acetyl glucosamine and glucuronic acid. Certain strains, particularly those of the M18 serotype, produce abundant amounts of capsule, resulting in formation of large, wet-appearing, translucent or "mucoid" colonies on solid media, whereas strains of M-types 4 and 22 produce none. Studies of acapsular mutant strains have provided evidence that the capsule enhances virulence in animal models of infection, an effect attributable, at least in part, to resistance to complement-mediated opsonophagocytic killing by leukocytes.

Blocking Neuronal Signaling to Immune Cells Treats Streptococcal Invasive Infection.

The nervous system, the immune system, and microbial pathogens interact closely at barrier tissues. Here, we find that a bacterial pathogen, Streptococcus pyogenes, hijacks pain and neuronal regulation of the immune response to promote bacterial survival. Necrotizing fasciitis is a life-threatening soft tissue infection in which "pain is out of proportion" to early physical manifestations.

Binding of NAD-Glycohydrolase to Streptolysin O Stabilizes Both Toxins and Promotes Virulence of Group A .

The globally dominant, invasive M1T1 strain of group A (GAS) harbors polymorphisms in the promoter region of an operon that contains the genes encoding streptolysin O (SLO) and NAD-glycohydrolase (NADase), resulting in high-level expression of these toxins. While both toxins have been shown experimentally to contribute to pathogenesis, many GAS isolates lack detectable NADase activity. DNA sequencing of such strains has revealed that reduced or absent enzymatic activity can be associated with a variety of point mutations in , the gene encoding NADase; a commonly observed polymorphism associated with near-complete abrogation of activity is a substitution of aspartic acid for glycine at position 330 (G330D).

Inhibition of Inflammasome-Dependent Interleukin 1β Production by Streptococcal NAD-Glycohydrolase: Evidence for Extracellular Activity.

Group A (GAS) is a common human pathogen and the etiologic agent of a large number of diseases ranging from mild, self-limiting infections to invasive life-threatening conditions. Two prominent virulence factors of this bacterium are the genetically and functionally linked pore-forming toxin streptolysin O (SLO) and its cotoxin NAD-glycohydrolase (NADase). Overexpression of these toxins has been linked to increased bacterial virulence and is correlated with invasive GAS disease.

NAD+-Glycohydrolase Promotes Intracellular Survival of Group A Streptococcus.

A global increase in invasive infections due to group A Streptococcus (S. pyogenes or GAS) has been observed since the 1980s, associated with emergence of a clonal group of strains of the M1T1 serotype. Among other virulence attributes, the M1T1 clone secretes NAD+-glycohydrolase (NADase).

The human antimicrobial peptide LL-37 binds directly to CsrS, a sensor histidine kinase of group A Streptococcus, to activate expression of virulence factors.

Group A Streptococcus (GAS) responds to subinhibitory concentrations of LL-37 by up-regulation of virulence factors through the CsrRS (CovRS) two-component system. The signaling mechanism, however, is unclear. To determine whether LL-37 signaling reflects specific binding to CsrS or rather a nonspecific response to LL-37-mediated membrane damage, we tested LL-37 fragments for CsrRS signaling and for GAS antimicrobial activity.

Group A streptococcal bacteremia without a source is associated with less severe disease in children.

We analyzed characteristics of 86 Group A streptococcal bacteremia cases at Boston Children's Hospital from 1992 to 2012. Twenty-three percent of children had severe disease, using intensive care unit admission (18), disability (7) or death (2) as indicators. Children with bacteremia without a source (30% of cases) were less likely to have severe disease than children with focal infections in adjusted models.

Streptolysin O and NAD-glycohydrolase prevent phagolysosome acidification and promote group A Streptococcus survival in macrophages.

Unlabelled: Group A Streptococcus (GAS, Streptococcus pyogenes) is an ongoing threat to human health as the agent of streptococcal pharyngitis, skin and soft tissue infections, and life-threatening conditions such as necrotizing fasciitis and streptococcal toxic shock syndrome. In animal models of infection, macrophages have been shown to contribute to host defense against GAS infection. However, as GAS can resist killing by macrophages in vitro and induce macrophage cell death, it has been suggested that GAS intracellular survival in macrophages may enable persistent infection.

BsaB, a novel adherence factor of group B Streptococcus.

Streptococcus agalactiae (group B Streptococcus [GBS]) is a leading cause of neonatal sepsis and meningitis, peripartum infections in women, and invasive infections in chronically ill or elderly individuals. GBS can be isolated from the gastrointestinal or genital tracts of up to 30% of healthy adults, and infection is thought to arise from invasion from a colonized mucosal site. Accordingly, bacterial surface components that mediate attachment of GBS to host cells or the extracellular matrix represent key factors in the colonization and infection of the human host.