How older adults manage misinformation and information overload - A qualitative study.

BACKGROUND: The COVID-19 pandemic was characterized by an abundance of information, some of it reliable and some of it misinformation. Evidence-based data on the impact of misinformation on attitudes and behaviours remains limited. Studies indicate that older adults are more likely to embrace and disseminate misinformation than other population groups, making them vulnerable to misinformation. The purpose of this article is to explore the effects of misinformation and information overload on older adults, and to present the management strategies put in place to deal with such effects, in the context of COVID-19. METHODS: A qualitative exploratory approach was adopted to conduct this research. A total of 36 semi-structured interviews were conducted with older adults living in Quebec, Canada. The interviews were fully transcribed and subjected to a thematic content analysis. RESULTS: Participants said they could easily spot misinformation online. Despite this, misinformation and its treatment by the media could generate fear, stress and anxiety. Moreover, the polarization induced by misinformation resulted in tensions and even friendship breakdowns. Participants also denounced the information overload produced largely by the media. To this end, the participants set up information routines targeting the sources of information and the times at which they consulted the information. CONCLUSIONS: This article questions the concept of vulnerability to misinformation by highlighting older adults' agency in managing misinformation and information overload. Furthermore, this study invites us to rethink communication strategies by distinguishing between information overload and misinformation.

Identifying genetic determinants of Streptococcus pyogenes-host interactions in a murine intact skin infection model.

Streptococcus pyogenes is an obligate human pathobiont associated with many disease states. Here, we present a model of S. pyogenes infection using intact murine epithelium. We were able to perform RNA sequencing to evaluate genetic changes undertaken by both the bacterium and host at 5 and 24 h post-infection. Analysis of these genomic data demonstrate that S. pyogenes undergoes genetic adaptation to successfully infect the murine epithelium, including changes to metabolism and activation of the Rgg2/Rgg3 quorum-sensing (QS) system. Subsequent experiments demonstrate that an intact Rgg2/Rgg3 QS cascade is necessary to establish a stable superficial skin infection. QS cascade activation results in increased murine morbidity and bacterial burden on the skin. This phenotype is associated with gross changes to the murine skin and with evidence of inflammation. These experiments offer a method to investigate S. pyogenes-epithelial interactions and demonstrate that a well-studied QS pathway is critical to a persistent infection.

Quorum Sensing Regulation of a Major Facilitator Superfamily Transporter Affects Multiple Streptococcal Virulence Factors.

Cell-cell signaling mediated by Rgg-family transcription factors and their cognate pheromones is conserved in Firmicutes, including all streptococci. In Streptococcus pyogenes, or group A strep (GAS), one of these systems, the Rgg2/3 quorum sensing (QS) system, has been shown to regulate phenotypes, including cellular aggregation and biofilm formation, lysozyme resistance, and macrophage immunosuppression. Here, we show the abundance of several secreted virulence factors (streptolysin O, SpyCEP, and M protein) decreases upon induction of QS. The main mechanism underlying the changes in protein levels appears to be transcriptional, occurs downstream of the QS circuit, and is dysregulated by the deletion of an Rgg2/3 QS-regulated major facilitator superfamily (MFS) transporter. Additionally, we identify this MFS transporter as the factor responsible for a previously observed increase in aminoglycoside sensitivity in QS-induced cells. IMPORTANCE The production of virulence factors is a tightly regulated process in bacterial pathogens. Efforts to elucidate the mechanisms by which genes are regulated may advance the understanding of factors influencing pathogen behavior or cellular physiology. This work finds expression of a major facilitator superfamily (MFS) transporter, which is governed by a quorum sensing (QS) system, impacts the expression of multiple virulence factors and accounts for QS-dependent antibiotic susceptibility. Although the mechanism underlying this effect is not clear, MFS orthologs with high sequence similarity from S. pneumoniae and S. porcinus were unable to substitute indicating substrate specificity of the GAS MFS gene. These findings demonstrate novel associations between expression of a transmembrane transporter and virulence factor expression and aminoglycoside transport.

Further delineation of the clinical spectrum of KAT6B disorders and allelic series of pathogenic variants.

PURPOSE: Genitopatellar syndrome and Say-Barber-Biesecker-Young-Simpson syndrome are caused by variants in the KAT6B gene and are part of a broad clinical spectrum called KAT6B disorders, whose variable expressivity is increasingly being recognized. METHODS: We herein present the phenotypes of 32 previously unreported individuals with a molecularly confirmed diagnosis of a KAT6B disorder, report 24 new pathogenic KAT6B variants, and review phenotypic information available on all published individuals with this condition. We also suggest a classification of clinical subtypes within the KAT6B disorder spectrum. RESULTS: We demonstrate that cerebral anomalies, optic nerve hypoplasia, neurobehavioral difficulties, and distal limb anomalies other than long thumbs and great toes, such as polydactyly, are more frequently observed than initially reported. Intestinal malrotation and its serious consequences can be present in affected individuals. Additionally, we identified four children with Pierre Robin sequence, four individuals who had increased nuchal translucency/cystic hygroma prenatally, and two fetuses with severe renal anomalies leading to renal failure. We also report an individual in which a pathogenic variant was inherited from a mildly affected parent. CONCLUSION: Our work provides a comprehensive review and expansion of the genotypic and phenotypic spectrum of KAT6B disorders that will assist clinicians in the assessment, counseling, and management of affected individuals.

Preoperative oral antibiotic bowel preparation in elective resectional colorectal surgery reduces rates of surgical site infections: a single-centre experience with a cost-effectiveness analysis.

INTRODUCTION: Surgical site infections cause considerable postoperative morbidity and mortality. The aim of this study was to determine the effect on surgical site infection rates following introduction of a departmental oral antibiotic bowel preparation protocol. METHODS: A prospective single-centre study was performed for elective colorectal resections between May 2016-April 2018; with a control group with mechanical bowel preparation and treatment group with oral antibiotic bowel preparation (neomycin and metronidazole) and mechanical bowel preparation. The primary outcome of surgical site infection and secondary outcomes of anastomotic leak, length of stay and mortality rate were analysed using Fisher's exact test and independent samples t-tests. A cost-effectiveness analysis was also performed. RESULTS: A total of 311 patients were included; 156 in the mechanical bowel preparation group and 155 in the mechanical bowel preparation plus oral antibiotic bowel preparation group. The study included 180 (57.9%) men and 131 (42.1%) women with a mean age of 68 years. There was a significant reduction in surgical site infection rates (mechanical bowel preparation 16.0% vs mechanical bowel preparation plus oral antibiotic bowel preparation 4.5%; P = 0.001) and mean length of stay (mechanical bowel preparation 10.2 days vs mechanical bowel preparation plus oral antibiotic bowel preparation 8.2 days; P = 0.012). There was also a reduction in anastomotic leak and mortality rates. Subgroup analyses demonstrated significantly reduced surgical site infection rates in laparoscopic resections (P = 0.008). There was an estimated cost saving of £239.13 per patient and £37,065 for our institution over a one-year period. CONCLUSION: Oral antibiotic bowel preparation is a feasible and cost-effective intervention shown to significantly reduce the rates of surgical site infection and length of stay in elective colorectal surgery.

The Influence of Maternal Schizotypy on the perception of Facial Emotional Expressions during Infancy: an Event-Related Potential Study.

Parenting directly affects the developmental and clinical outcomes of children. How parental personality relates to perceptual and cognitive mechanisms during early development is not clear. For parents with traits of the personality dimension schizotypy, would their infant display brain responses similar to those on the schizophrenia-spectrum? This study investigates whether maternal personality influences early social-cognitive awareness during the first 6 postnatal months. Schizotypy is a dimension of personality within the general population. If deficits contribute to the development of schizophrenia-spectrum disorders by influencing the development of symptom-like characteristics, they may be observable in neurotypical individuals with schizotypal characteristics. Parents and their infants were shown standardised positive and negative faces and event-related potential responses were assessed. It was hypothesised that the infants of schizotypic mothers would display differential Negative-central event-related potentials for the happy and fearful expressions when compared to infants of non-schizotypic mothers. Results support prior literature; indicating 6-month-old infants allocate more attentional resources to fearful when contrasted to happy faces. The adult cohort displays this same ability. In addition, schizotypic mothers displayed comparable amplitudes for both expressions in comparison to the control mothers who exhibited larger amplitudes towards the fearful compared to the happy expression. Infants of schizotypic mothers did not show a greater sensitivity to facial expressions at 6-months, but schizotypic mothers showed a generalised response towards facial expressions compared to the typical P600 response illustrated by the control mothers. The present study suggests that development in the higher cognitive domains, such as the allocation of attention to novel stimuli, are not affected at 6 months of age by maternal personality related to schizotypy when examined at the group level. Implications for personality development, maternal-infant interactions and cognitive neuroscience methodologies are discussed.

Differences in Chest Measurements between the Cis-female and Trans-female Chest Exposed to Estrogen and Its Implications for Breast Augmentation.

BACKGROUND: Gender confirming primary breast augmentation is becoming more common. The purpose of this study was to compare the demographic and anatomical differences in cis-female and trans-female populations. METHODS: This was a retrospective analysis of trans-female patients and cis-female patients undergoing primary breast augmentation at a single institution. Analysis included patient demographics and preoperative chest measurements including sternal notch to nipple distance (SSN), breast width (BW), nipple to inframammary fold distance (N-IMF), and nipple to midline distance (N-M). Continuous variables were compared using independent t tests, and discrete variables were compared using Pearson's χ2 tests. RESULTS: Eighty-two trans-female and 188 cis-female patients undergoing primary breast augmentation were included. Trans-female patients were older (40.37 versus 34.07), more likely to have psychological comorbidities (50% versus 12.23%), and had a higher body mass index, 27.46 kg/m2 versus 22.88 kg/m2 (P = 1.91E-07), than cis-female patients. Cis-female patients most commonly had an ectomorph body habitus (52% versus 26%), whereas trans-female patients most commonly had an endomorph body habitus (40% versus 7%). Pseudoptosis or ptosis was more commonly seen in cis-female patients (P = 0.0056). There were significant differences in preoperative breast measurements including sternal notch to nipple distance, BW, and N-M between groups, but not in N-IMF. The ratio of BW/N-IMF was statistically significant (P = 2.65E-07 on right), indicating that the similarity in N-IMF distance did not adjust for the difference in BW. CONCLUSIONS: The trans-female and cis-female populations seeking primary breast augmentation have significant demographic and anatomical differences. This has implications for surgical decision-making and planning to optimize outcomes for trans-female patients.

Streptococcus endopeptidases promote HPV infection in vitro.

Both cervical and throat cancers are associated with human papillomavirus (HPV). HPV infection requires cleavage of the minor capsid protein L2 by furin. While furin is present in the vaginal epithelium, it is absent in oral epithelial basal cells where HPV infection occurs. The objective of this study was to investigate whether common oral bacteria express furin-like peptidases. By screening strains representing 12 oral Streptococcus and Enterococcus species, we identified that eight Streptococcus strains displayed high levels of furin-like peptidase activity, with S. gordonii V2016 the highest. We constructed null mutations for 14 genes encoding putative endopeptidases in S. gordonii V2016. Results showed that three endopeptidases, PepO, PulO, and SepM, had furin-like activities. All three mutants showed decreased natural transformation by chromosomal DNA, while the pepO mutant also showed reduced transformation by plasmid DNA, indicating involvement of these endopeptidases in competence development. The purified S. gordonii PepO protein promoted infection of epithelial 293TT cells in vitro by HPV16 pseudovirus. In conclusion, oral bacteria might promote HPV infection and contribute to HPV tissue tropism and subsequent carcinogenesis in the oral cavity and throat by providing furin-like endopeptidases.

Response to Scheel et al.

Scheel et al.[1] highlight three types of methodological concern with the work reported in our recent paper [2], related to analytical decisions, fetal behavior, and how light interfaces with maternal tissue. Here we outline why the issues raised do not detract from our originally reported conclusions. In our view, the procedural and analytical decisions that we made in our study [2] were the most appropriate given the uncharted territory that we explored. The best test of methodological robustness of our approach would be replication by another laboratory.

A Quorum Sensing-Regulated Protein Binds Cell Wall Components and Enhances Lysozyme Resistance in Streptococcus pyogenes.

The Rgg2/3 quorum sensing (QS) system is conserved among all sequenced isolates of group A Streptococcus (GAS; Streptococcus pyogenes). The molecular architecture of the system consists of a transcriptional activator (Rgg2) and a transcriptional repressor (Rgg3) under the control of autoinducing peptide pheromones (SHP2 and SHP3). Activation of the Rgg2/3 pathway leads to increases in biofilm formation and resistance to the bactericidal effects of the host factor lysozyme. In this work, we show that deletion of a small gene, spy49_0414c, abolished both phenotypes in response to pheromone signaling. The gene encodes a small, positively charged, secreted protein, referred to as StcA. Analysis of recombinant StcA showed that it can directly interact with GAS cell wall preparations containing phosphodiester-linked carbohydrate polymers but not with preparations devoid of them. Immunofluorescence microscopy detected antibody against StcA bound to the surface of paraformaldehyde-fixed wild-type cells. Expression of StcA in bacterial culture induced a shift in the electrostatic potential of the bacterial cell surface, which became more positively charged. These results suggest that StcA promotes phenotypes by way of ionic interactions with the GAS cell wall, most likely with negatively charged cell wall-associated polysaccharides.IMPORTANCE This study focuses on a small protein, StcA, that is expressed and secreted under induction of Rgg2/3 QS, ionically associating with negatively charged domains on the cell surface. These data present a novel mechanism of resistance to the host factor lysozyme by GAS and have implications in the relevance of this circuit in the interaction between the bacterium and the human host that is mediated by the bacterial cell surface.

Activating mutations in quorum-sensing regulator Rgg2 and its conformational flexibility in the absence of an intermolecular disulfide bond.

Rap/Rgg/NprR/PlcR/PrgX (RRNPP) quorum-sensing systems use extracellular peptide pheromones that are detected by cytoplasmic receptors to regulate gene expression in firmicute bacteria. Rgg-type receptors are allosterically regulated through direct pheromone binding to control transcriptional activity; however, the receptor activation mechanism remains poorly understood. Previous work has identified a disulfide bond between Cys-45 residues within the homodimer interface of Rgg2 from Streptococcus dysgalactiae (Rgg2Sd). Here, we compared two Rgg2Sd(C45S) X-ray crystal structures with that of wild-type Rgg2Sd and found that in the absence of the intermolecular disulfide, the Rgg2Sd dimer interface is destabilized and Rgg2Sd can adopt multiple conformations. One conformation closely resembled the "disulfide-locked" Rgg2Sd secondary and tertiary structures, but another displayed more extensive rigid-body shifts as well as dramatic secondary structure changes. In parallel experiments, a genetic screen was used to identify mutations in rgg2 of Streptococcus pyogenes (rgg2Sp ) that conferred pheromone-independent transcriptional activation of an Rgg2-stimulated promoter. Eight mutations yielding constitutive Rgg2 activity, designated Rgg2Sp*, were identified, and five of them clustered in or near an Rgg2 region that underwent conformational changes in one of the Rgg2Sd(C45S) crystal structures. The Rgg2Sp* mutations increased Rgg2Sp sensitivity to pheromone and pheromone variants while displaying decreased sensitivity to the Rgg2 antagonist cyclosporine A. We propose that Rgg2Sp* mutations invoke shifts in free-energy bias to favor the active state of the protein. Finally, we present evidence for an electrostatic interaction between an N-terminal Asp of the pheromone and Arg-153 within the proposed pheromone-binding pocket of Rgg2Sp.

Evolutionary Constraints Shaping Streptococcus pyogenes-Host Interactions.

Research on the Gram-positive human-restricted pathogen Streptococcus pyogenes (Group A Streptococcus, GAS) has long focused on invasive illness, the most severe manifestations of GAS infection. Recent advances in descriptions of molecular mechanisms of GAS virulence, coupled with massive sequencing efforts to isolate genomes, have allowed the field to better understand the molecular and evolutionary changes leading to pandemic strains. These findings suggest that it is necessary to rethink the dogma involving GAS pathogenesis, and that the most productive avenues for research going forward may be investigations into GAS in its 'normal' habitat, the nasopharynx, and its ability to either live with its host in an asymptomatic lifestyle or as an agent of superficial infections. This review will consider these advances, focusing on the natural history of GAS, the evolution of pandemic strains, and novel roles for several key virulence factors that may allow the field to better understand their physiological role.

Inoculation site leprosy in a tattoo as a paradoxical reaction following tuberculosis treatment.

We present a patient who developed inoculation site leprosy in a tattoo, which was confirmed by Mycobacterium leprae DNA sequencing of a polymerase chain reaction product from a skin biopsy. His leprosy became manifest as a paradoxical reaction only after 8 weeks of treatment for pulmonary tuberculosis.

PepO, a CovRS-controlled endopeptidase, disrupts Streptococcus pyogenes quorum sensing.

Group A Streptococcus (GAS, Streptococcus pyogenes) is a human-restricted pathogen with a capacity to both colonize asymptomatically and cause illnesses ranging from pharyngitis to necrotizing fasciitis. An understanding of how and when GAS switches between genetic programs governing these different lifestyles has remained an enduring mystery and likely requires carefully tuned environmental sensors to activate and silence genetic schemes when appropriate. Herein, we describe the relationship between the Control of Virulence (CovRS, CsrRS) two-component system and the Rgg2/3 quorum-sensing pathway. We demonstrate that responses of CovRS to the stress signals Mg(2+) and a fragment of the antimicrobial peptide LL-37 result in modulated activity of pheromone signaling of the Rgg2/3 pathway through a means of proteolysis of SHP peptide pheromones. This degradation is mediated by the cytoplasmic endopeptidase PepO, which is the first identified enzymatic silencer of an RRNPP-type quorum-sensing pathway. These results suggest that under conditions in which the virulence potential of GAS is elevated (i.e. enhanced virulence gene expression), cellular responses mediated by the Rgg2/3 pathway are abrogated and allow individuals to escape from group behavior. These results also indicate that Rgg2/3 signaling is instead functional during non-virulent GAS lifestyles.

Novel antibody associations in immune-mediated necrotising myopathy without inflammation.

INTRODUCTION: The patient presenting with proximal muscle weakness, elevated serum creatinine kinase and myopathic electromyography and biopsy findings has a wide differential diagnosis that includes toxic, autoimmune, paraneoplastic and congenital myopathies. Autoimmune myopathies are important to identify because they may respond to immunosuppressive therapies. METHODS: We describe two cases of immune-mediated necrotizing myopathy each associated with a novel antibody. RESULTS: Case 1 describes a progressive myopathy in a statin user. Antibodies to 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase were identified and the patient responded to steroid therapy. Case 2 describes an aggressive myopathy associated with antibodies to signal recognition particle. There was no response to steroids. Clinical improvement followed treatment with rituximab and cyclophosphamide. CONCLUSION: The identification of myositis-specific antibodies is important because they are associated with distinct clinical phenotypes and may guide the physician in terms of treatment strategies.

Thymic Nurse Cells Participate in Heterotypic Internalization and Repertoire Selection of Immature Thymocytes; Their Removal from the Thymus of Autoimmune Animals May be Important to Disease Etiology.

Thymic nurse cells (TNCs) are specialized epithelial cells that reside in the thymic cortex. The initial report of their discovery in 1980 showed TNCs to contain up to 200 thymocytes within specialized vacuoles in their cytoplasm. Much has been reported since that time to determine the function of this heterotypic internalization event that exists between TNCs and developing thymocytes. In this review, we discuss the literature reported that describes the internalization event and the role TNCs play during T cell development in the thymus as well as why these multicellular complexes may be important in inhibiting the development of autoimmune diseases.

Functional and oncologic outcomes of graded bladder neck preservation during robot-assisted radical prostatectomy.

PURPOSE: To describe our bladder neck dissection during robot-assisted radical prostatectomy (RARP), to describe the degrees of robot-assisted bladder neck preservation (R-BNP) we have encountered, and to determine the effect of increasing R-BNP on postoperative continence and positive surgical margin (PSM) rates. PATIENTS AND METHODS: We performed a retrospective analysis of 599 patients who underwent robot-assisted radical prostatectomy (RARP) by a single surgeon (DIL). All bladder neck dissections were graded between 1 and 4; higher grades corresponded to an increasing degree of robot-assisted bladder neck preservation (R-BNP). After grouping patients by R-BNP grade, postoperative continence and positive surgical margin (PSM) rates were compared. The association between R-BNP and continence was also assessed using multivariate binary logistic regression models. RESULTS: Similar outcomes were seen for two definitions of continence (0 pads per day [ppd]; 0 ppd or security pad, respectively). A higher proportion of patients were continent at 3 months postoperatively who received grade 4 compared with grade 1 (P=0.043; P=0.001) and grade 2 (P=0.006; P=0.009); and grade 3 compared with grade 1 (P=0.048; P=0.002) and grade 2 (P=0.009; P=0.030) R-BNP. There was no difference between grade 1 and 2 (P=0.541; P=0.064), and grade 3 and 4 (P=0.898; P=0.584) R-BNP. At 1 year postoperatively, there was no difference among the four groups in continence rate (P=0.771; P=0.411). R-BNP was an independent predictor of continence at 3 months (odds ratio [OR] [95% confidence interval (CI)]=1.33 [1.06-1.67]; OR [95% CI]=1.45 [1.1-1.82]), but not at 1 year (OR [95% CI]=1.07 [0.82-1.39]; OR (95% CI)=1.30 [0.92-1.85]). There was no difference among the four groups in PSM rates (P=0.946). CONCLUSIONS: R-BNP is a graded, rather than all-or-none outcome. An increasing degree of R-BNP is associated with an earlier return to continence, without compromising oncologic outcomes.

Role of microparticles in sepsis.

This review discusses the role of microparticles in inflammation, coagulation, vascular function, and most importantly, their physiological and pathological functions in sepsis. Microparticles are proinflammatory, procoagulant membrane vesicles released from various cell types. They are detectable in normal individuals and basal levels correlate with a balance between cell proliferation, stimulation, and destruction. Haemostatic imbalance leads to various pathological states of inflammation and thrombosis including cardiovascular disease and sepsis, where circulating microparticles display both an increase in number and phenotypic change. Microparticles, mainly of platelet origin enable both local and disseminated amplification of the haemostatic response to endothelial injury through exposure of phosphatidylserine, tissue factor, and coagulation factor binding sites. Surface expression of membrane antigens by microparticles facilitates cytoadhesion, chemotaxis, and cytokine secretion to drive a proinflammatory response. Microparticles behave as vectors in the transcellular exchange of biological information and are important regulators of endothelial function and angiogenesis. The extent to which circulating microparticles contribute to the pathogenesis of sepsis and disseminated intravascular coagulation is currently unknown. Microparticles may in fact be beneficial in early sepsis, given that activated protein C bound to endothelium-derived microparticles retains anticoagulant activity, and increased circulating microparticles are protective against vascular hyporeactivity. Elevated levels of microparticles in early sepsis may therefore compensate for the host's systemic inflammatory response. Importantly, in vivo, septic microparticles induce deleterious changes in the expression of enzyme systems related to inflammation and oxidative stress, thus they may represent important contributors to multi-organ failure in septic shock.