Enterococcus faecalis Endocarditis Severity in Rabbits Is Reduced by IgG Fabs Interfering with Aggregation Substance

Background: Enterococcus faecalis is a significant cause of infective endocarditis, an infection of the heart endothelium leading to vegetation formation (microbes, fibrin, platelets, and host cells attached to underlying endothelial tissue). Our previous research determined that enterococcal aggregation substance (AS) is an important virulence factor in causation of endocarditis, although endocarditis may occur in the absence of AS production. Production of AS by E. faecalis causes the organism to form aggregates through AS binding to enterococcal binding substance. In this study, we assessed the ability of IgGs and IgG Fabs against AS to provide protection against AS + E. faecalis endocarditis. Methodology/Principal Findings: When challenged with AS + E. faecalis, 10 rabbits actively immunized against AS + E. faecalis developed more significant vegetations than 9 animals immunized against AS 2 E. faecalis, and 9/10 succumbed compared to 2/9 (p,0.005), suggesting enhanced aggregation by IgG contributes significantly to disease. IgG antibodies against AS also enhanced enterococcal aggregation as tested in vitro. In contrast, Fab fragments of IgG from rabbits immunized against purified AS, when passively administered to rabbits (6/group) immediately before challenge with AS + E. faecalis, reduced total vegetation (endocarditis lesion) microbial counts (7.9610 6 versus 2.0610 5, p = 0.02) and size (40 mg versus 10, p = 0.05). In vitro, the Fabs prevented enterococcal aggregation. Conclusions/Significance: The data confirm the role of AS in infective endocarditis formation and suggest that use of Fab

STAT3 regulates the onset of oxidant-induced senescence in lung fibroblasts

Copyright © 2019 by the American Thoracic Society. Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease of unknown cause with a median survival of only 3 years. Other investigators and we have shown that fibroblasts derived from IPF lungs display characteristics of senescent cells, and that dysregulated activation of the transcription factor signal transducer and activator of transcription 3 (STAT3) correlates with IPF progression. The question of whether STAT3 activation is involved in fibroblast senescence remains unanswered. We hypothesized that inhibiting STAT3 activation after oxidantinduced senescence would attenuate characteristics of the senescent phenotype. We aimed to characterize a model of oxidant-induced senescence in human lung fibroblasts and to determine the effect of inhibiting STAT3 activity on the development of senescence. Exposing human lung fibroblasts to 150 μM hydrogen peroxide (H2O2) resulted in increased senescence-associated β-galactosidase content and expression of p21 and IL-6, all of which are features of senescence. The shift into senescence was accompanied by an increase of STAT3 translocation to the nucleus and mitochondria. Additionally, Seahorse analysis provided evidence of increased mitochondrial respiration characterized by increased basal respiration, proton leak, and an associated increase in superoxide (O2-) production in senescent fibroblasts. Targeting STAT3 activity using the small-molecule inhibitor STA-21 attenuated IL-6 production, reduced p21 levels, decreased senescence-associated b-galactosidase accumulation, and restored normalmitochondrial function. The results of this study illustrate that stress-induced senescence in lung fibroblasts involves the activation of STAT3, which can be pharmacologically modulated

Outcomes of COVID-19 related hospitalization among people with HIV in the ISARIC WHO Clinical Characterization Protocol (UK): a prospective observational study

BACKGROUND: Evidence is conflicting about how HIV modulates COVID-19. We compared the presentation characteristics and outcomes of adults with and without HIV who were hospitalized with COVID-19 at 207 centers across the United Kingdom and whose data were prospectively captured by the ISARIC WHO CCP study. METHODS: We used Kaplan-Meier methods and Cox regression to describe the association between HIV status and day-28 mortality, after separate adjustment for sex, ethnicity, age, hospital acquisition of COVID-19 (definite hospital acquisition excluded), presentation date, ten individual comorbidities, and disease severity at presentation (as defined by hypoxia or oxygen therapy). RESULTS: Among 47,592 patients, 122 (0.26%) had confirmed HIV infection and 112/122 (91.8%) had a record of antiretroviral therapy. At presentation, HIV-positive people were younger (median 56 versus 74 years; p<0.001) and had fewer comorbidities, more systemic symptoms and higher lymphocyte counts and C-reactive protein levels. The cumulative day-28 mortality was similar in the HIV-positive vs. HIV-negative groups (26.7% vs. 32.1%; p=0.16), but in those under 60 years of age HIV-positive status was associated with increased mortality (21.3% vs. 9.6%; p<0.001 [log-rank test]). Mortality was higher among people with HIV after adjusting for age (adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.01-2.14; p=0.05), and the association persisted after adjusting for the other variables (aHR 1.69; 95% CI 1.15-2.48; p=0.008) and when restricting the analysis to people aged <60 years (aHR 2.87; 95% CI 1.70-4.84; p<0.001). CONCLUSIONS: HIV-positive status was associated with an increased risk of day-28 mortality among patients hospitalized for COVID-19

Scapular deformity in obstetric brachial plexus palsy: a new finding

While most obstetric brachial plexus palsy patients recover arm and hand function, the residual nerve weakness leads to muscle imbalances about the shoulder which may cause bony deformities. In this paper we describe abnormalities in the developing scapula and the glenohumeral joint. We introduce a classification for the deformity which we term Scapular Hypoplasia, Elevation and Rotation. Multiple anatomic parameters were measured in bilateral CT images and three-dimensional CT reconstruction of the shoulder girdle of 30 obstetric brachial plexus palsy patients (age range 10 months–10.6 years). The affected scapulae were found to be hypoplastic by an average of 14% while the ratio of the height to the width of the body of scapula (excluding acromion) were not significantly changed, the acromion was significantly elongated by an average of 19%. These parameters as well as subluxation of the humeral head (average 14%) and downward rotation in the scapular plane were found to correlate with the area of scapula visible over the clavicle. This finding provides a classification tool for diagnosis and objective evaluation of the bony deformity and its severity in obstetric brachial plexus palsy patients

A preliminary study of genetic factors that influence susceptibility to bovine tuberculosis in the British cattle herd

Associations between specific host genes and susceptibility to Mycobacterial infections such as tuberculosis have been reported in several species. Bovine tuberculosis (bTB) impacts greatly the UK cattle industry, yet genetic predispositions have yet to be identified. We therefore used a candidate gene approach to study 384 cattle of which 160 had reacted positively to an antigenic skin test (‘reactors’). Our approach was unusual in that it used microsatellite markers, embraced high breed diversity and focused particularly on detecting genes showing heterozygote advantage, a mode of action often overlooked in SNP-based studies. A panel of neutral markers was used to control for population substructure and using a general linear model-based approach we were also able to control for age. We found that substructure was surprisingly weak and identified two genomic regions that were strongly associated with reactor status, identified by markers INRA111 and BMS2753. In general the strength of association detected tended to vary depending on whether age was included in the model. At INRA111 a single genotype appears strongly protective with an overall odds ratio of 2.2, the effect being consistent across nine diverse breeds. Our results suggest that breeding strategies could be devised that would appreciably increase genetic resistance of cattle to bTB (strictly, reduce the frequency of incidence of reactors) with implications for the current debate concerning badger-culling

Quality of life and illness perception in working and sick-listed chronic RSI patients

OBJECTIVE: To study differences between working and sick-listed chronic repetitive strain injury (RSI) patients in the Netherlands with respect to indices of quality of life and illness perception. METHODS: In a cross-sectional design, one questionnaire was sent to all 3,250 members of the national RSI patient association. For descriptive purposes, demographics, work status and complaint-related variables such as severity, type, duration, and extent of complaints were asked for. Indices of quality of life were assessed through seven SF-36 subscales (physical (role) functioning, emotional role functioning, social functioning, pain, mental health and vitality). A work-ability estimate and VAS scales were used to assess complaint-related decrease in quality of life. Illness perception was assessed through the brief illness perception questionnaire (IPQ-B). Working patients and sick-listed patients were identified. Tests between the two independent groups were performed and P-values < 0.01 were considered significant. RESULTS: Data from 1,121 questionnaires were used. Two-thirds of the respondents worked and one-third were sick-listed. Average duration of complaints was over 5 years in both groups. The sick-listed patients reported significantly more severe and extensive complaints than did the working patients. In addition, sick-listed patients reported significantly poorer mental health, physical (role) functioning, emotional role functioning, pain, vitality, and work-ability. With respect to illness perception, both groups showed the same concerns about their complaints, but sick-listed patients had significantly more distorted perceptions in their emotional response, identity, treatment control, personal control, timeline, and life consequences. Complaint-related decrease in quality of life was 31% in the working patients and 49% in the sick-listed patients. CONCLUSION: The study found a greater number and severe complaints among sick-listed chronic RSI patients and a considerably decreased quality of life because of their complaints. These findings may allow for a better treatment focus in the futur

Interpretation of ambiguous situations: evidence for a dissociation between social and physical threat in Williams syndrome

There is increasing evidence that Williams syndrome (WS) is associated with elevated anxiety that is non-social in nature, including generalised anxiety and fears. To date very little research has examined the cognitive processes associated with this anxiety. In the present research, attentional bias for non-social threatening images in WS was examined using a dot-probe paradigm. Participants were 16 individuals with WS aged between 13 and 34 years and two groups of typically developing controls matched to the WS group on chronological age and attentional control ability respectively. The WS group exhibited a significant attention bias towards threatening images. In contrast, no bias was found for group matched on attentional control and a slight bias away from threat was found in the chronological age matched group. The results are contrasted with recent findings suggesting that individuals with WS do not show an attention bias for threatening faces and discussed in relation to neuroimaging research showing elevated amygdala activation in response to threatening non-social scenes in WS

Multidisciplinary teams, and parents, negotiating common ground in shared-care of children with long-term conditions: A mixed methods study

Background: Limited negotiation around care decisions is believed to undermine collaborative working between parents of children with long-term conditions and professionals, but there is little evidence of how they actually negotiate their respective roles. Using chronic kidney disease as an exemplar this paper reports on a multi-method study of social interaction between multidisciplinary teams and parents as they shared clinical care. Methods. Phases 1 and 2: a telephone survey mapping multidisciplinary teams' parent-educative activities, and qualitative interviews with 112 professionals (Clinical-psychologists, Dietitians, Doctors, Nurses, Play-specialists, Pharmacists, Therapists and Social-workers) exploring their accounts of parent-teaching in the 12 British children's kidney units. Phase 3: six ethnographic case studies in two units involving observations of professional/parent interactions during shared-care, and individual interviews. We used an analytical framework based on concepts drawn from Communities of Practice and Activity Theory. Results: Professionals spoke of the challenge of explaining to each other how they are aware of parents' understanding of clinical knowledge, and described three patterns of parent-educative activity that were common across MDTs: Engaging parents in shared practice; Knowledge exchange and role negotiation, and Promoting common ground. Over time, professionals had developed a shared repertoire of tools to support their negotiations with parents that helped them accomplish common ground during the practice of shared-care. We observed mutual engagement between professionals and parents where a common understanding of the joint enterprise of clinical caring was negotiated. Conclusions: For professionals, making implicit knowledge explicit is important as it can provide them with a language through which to articulate more clearly to each other what is the basis of their intuition-based hunches about parents' support needs, and may help them to negotiate with parents and accelerate parents' learning about shared caring. Our methodology and results are potentially transferrable to shared management of other conditions. © 2013 Swallow et al.; licensee BioMed Central Ltd

Coracoid Abnormalities and Their Relationship with Glenohumeral Deformities in Children with Obstetric Brachial Plexus Injury

<p>Abstract</p> <p>Background</p> <p>Patients with incomplete recovery from obstetric brachial plexus injury (OBPI) usually develop secondary muscle imbalances and bone deformities at the shoulder joint. Considerable efforts have been made to characterize and correct the glenohumeral deformities, and relatively less emphasis has been placed on the more subtle ones, such as those of the coracoid process. The purpose of this retrospective study is to determine the relationship between coracoid abnormalities and glenohumeral deformities in OBPI patients. We hypothesize that coracoscapular angles and distances, as well as coracohumeral distances, diminish with increasing glenohumeral deformity, whereas coracoid overlap will increase.</p> <p>Methods</p> <p>39 patients (age range: 2-13 years, average: 4.7 years), with deformities secondary to OBPI were included in this study. Parameters for quantifying coracoid abnormalities (coracoscapular angle, coracoid overlap, coracohumeral distance, and coracoscapular distance) and shoulder deformities (posterior subluxation and glenoid retroversion) were measured on CT images from these patients before any surgical intervention. Paired Student t-tests and Pearson correlations were used to analyze different parameters.</p> <p>Results</p> <p>Significant differences between affected and contralateral shoulders were found for all coracoid and shoulder deformity parameters. Percent of humeral head anterior to scapular line (PHHA), glenoid version, coracoscapular angles, and coracoscapular and coracohumeral distances were significantly lower for affected shoulders compared to contralateral ones. Coracoid overlap was significantly higher for affected sides compared to contralateral sides. Significant and positive correlations were found between coracoscapular distances and glenohumeral parameters (PHHA and version), as well as between coracoscapular angles and glenohumeral parameters, for affected shoulders. Moderate and positive correlations existed between coracoid overlap and glenohumeral parameters for affected shoulders. On the contrary, all correlations between the coracoid and glenohumeral parameters for contralateral shoulders were only moderate or relatively low.</p> <p>Conclusions</p> <p>These results indicate that the spatial orientation of the coracoid process differs significantly between affected and contralateral shoulders, and it is highly correlated with the glenohumeral deformity. With the progression of glenohumeral deformity, the coracoid process protrudes more caudally and follows the subluxation of the humeral head which may interfere with the success of repositioning the posteriorly subluxed humeral head anteriorly to articulate with the glenoid properly.</p