Sialylation of campylobacter jejuni lipo-oligosaccharides: impact on phagocytosis and cytokine production in mice

<p>Background: Guillain-Barré syndrome (GBS) is a post-infectious polyradiculoneuropathy, frequently associated with antecedent Campylobacter jejuni (C. jejuni) infection. The presence of sialic acid on C. jejuni lipo-oligosaccharide (LOS) is considered a risk factor for development of GBS as it crucially determines the structural homology between LOS and gangliosides, explaining the induction of cross-reactive neurotoxic antibodies. Sialylated C. jejuni are recognised by TLR4 and sialoadhesin; however, the functional implications of these interactions in vivo are unknown.</p> <p>Methodology/Principal Findings: In this study we investigated the effects of bacterial sialylation on phagocytosis and cytokine secretion by mouse myeloid cells in vitro and in vivo. Using fluorescently labelled GM1a/GD1a ganglioside-mimicking C. jejuni strains and corresponding (Cst-II-mutant) control strains lacking sialic acid, we show that sialylated C. jejuni was more efficiently phagocytosed in vitro by BM-MΦ, but not by BM-DC. In addition, LOS sialylation increased the production of IL-10, IL-6 and IFN-β by both BM-MΦ and BM-DC. Subsequent in vivo experiments revealed that sialylation augmented the deposition of fluorescent bacteria in splenic DC, but not macrophages. In addition, sialylation significantly amplified the production of type I interferons, which was independent of pDC.</p> <p>Conclusions/Significance: These results identify novel immune stimulatory effects of C. jejuni sialylation, which may be important in inducing cross-reactive humoral responses that cause GBS</p&gt

Patient and public involvement (PPI) in UK surgical trials: a survey and focus groups with stakeholders to identify practices, views, and experiences

Background and aims Historically, patient and public involvement (PPI) in the design and conduct of surgical trials has been absent or minimal, but it is now routinely recommended and even required by some research funders. We aimed to identify and describe current PPI practice in surgical trials in the United Kingdom, and to explore the views and experiences of surgical trial staff and patient or public contributors in relation to these practices. This was part of a larger study to inform development of a robust PPI intervention aimed at improving recruitment and retention in surgical trials. Methods Our study had two stages: 1) an online survey to identify current PPI practice in active UK-led, adult surgical trials; and 2) focus groups and interviews with key stakeholders (surgical trial investigators, administrators, and patient or public contributors) to explore their views and experiences of PPI. Results Of 129 eligible surgical trial teams identified, 71 (55%) took part in the survey. In addition, 54 stakeholders subsequently took part in focus groups or interviews. Sixty-five (92%) survey respondents reported some kind of PPI, most commonly at the design and dissemination stages and in oversight or advisory roles. The single most common PPI activity was developing participant information sheets (72%). Participants reported mixed practice and views on a variety of issues including the involvement of patients versus lay members of the public, recruitment methods, use of role descriptions and payment for the time of PPI contributors. They suggested some solutions, including the use of written role descriptions and databases of potential PPI contributors to aid recruitment. Conclusions UK surgical trials involve patients and members of the public in a variety of different ways, most commonly at the beginning and end of the trial lifecycle and in oversight or advisory roles. These are not without challenges and there remain uncertainties about who best to involve, why, and how. Future research should aim to address these issues

Thinking about Later Life: Insights from the Capability Approach

A major criticism of mainstream gerontological frameworks is the inability of such frameworks to appreciate and incorporate issues of diversity and difference in engaging with experiences of aging. Given the prevailing socially structured nature of inequalities, such differences matter greatly in shaping experiences, as well as social constructions, of aging. I argue that Amartya Sen’s capability approach (2009) potentially offers gerontological scholars a broad conceptual framework that places at its core consideration of human beings (their values) and centrality of human diversity. As well as identifying these key features of the capability approach, I discuss and demonstrate their relevance to thinking about old age and aging. I maintain that in the context of complex and emerging identities in later life that shape and are shaped by shifting people-place and people-people relationships, Sen’s capability approach offers significant possibilities for gerontological research

Siglecg Limits the Size of B1a B Cell Lineage by Down-Regulating NFκB Activation

BACKGROUND: B1 B cells are believed to be a unique lineage with a distinct developmental pathway, function and activation requirement. How this lineage is genetically determined remained largely obscure. METHODS AND PRINCIPAL FINDINGS: Using the Siglecg-deficient mice with a knockin of green-fluorescent protein encoding sequence, we show here that, although the Siglecg gene is broadly expressed at high levels in all stages and/or lineages of B cells tested and at lower levels in other lineages, its deletion selectively expanded the B1a B cell lineages, including the frequency of the B1 cell progenitor in the bone marrow and the number of B1a cells in the peritoneal cavity, by postnatal expansion. The expansion of B1a B cells in the peritoneal correlated with enhanced activation of NFkappaB and was ablated by an IKK inhibitor. CONCLUSION AND SIGNIFICANCE: Our data revealed a critical role for Siglec G-NFkappaB pathway in regulating B1a B cell lineage. These data lead to a novel model of B1a lineage development that explains a large array of genetic data in this field

Children’s Gender Identity in Lesbian and Heterosexual Two-Parent Families

This study compared gender identity, anticipated future heterosexual romantic involvement, and psychosocial adjustment of children in lesbian and heterosexual families; it was furthermore assessed whether associations between these aspects differed between family types. Data were obtained in the Netherlands from children in 63 lesbian families and 68 heterosexual families. All children were between 8 and 12 years old. Children in lesbian families felt less parental pressure to conform to gender stereotypes, were less likely to experience their own gender as superior and were more likely to be uncertain about future heterosexual romantic involvement. No differences were found on psychosocial adjustment. Gender typicality, gender contentedness and anticipated future heterosexual romantic involvement were significant predictors of psychosocial adjustment in both family types

Intra-gastric balloon as an adjunct to lifestyle support in severely obese adolescents; Impact on weight, physical activity, cardio-respiratory fitness and psychosocial wellbeing.

BACKGROUND: Severe adolescent obesity (BMI>99.6th centile) is a significant public health challenge. Current non-invasive treatments, including community-based lifestyle interventions, are often of limited effectiveness in this population, with NICE guidelines suggesting the use of bariatric surgery as the last line of treatment (NICE, 2013). Health professionals are understandably reluctant to commission bariatric surgery and as an alternative, the use of an intra-gastric balloon as an adjunct to a lifestyle programme might offer a reversible, potentially safer and less invasive option. OBJECTIVES: Explore the use of an intra-gastric balloon as an adjunct to a lifestyle support programme, to promote weight loss in severely obese adolescents. Outcomes included Weight loss, Waist and Hip measurements, psychosocial outcomes including health related quality of life and physical self-perceptions, physical activity and cardiorespiratory fitness. METHOD: Non-randomised pilot study. Results: 12 severely obese adolescents (5 males, 7 females; mean age 15yrs; BMI >3.5 s.d.; puberty stage 4 or more) and their families were recruited. Mean weight loss at 12 months (n=9) was 3.05 kg±14.69; d=0.002, P=0.550, and a BMI Z-score (n=12) change of 0.2 s.d.; d=0.7, P=0.002 was observed at 6 months with a large effect, but was not sustained at 12 months (mean change 0.1 s.d.; d=0.3, P=0.146 ) At 24 months (n=10) there was a weight gain from baseline of +9.9 kg±1.21 (d=0.4; P=0.433). Adolescent and parent HRQoL scores exceeded the minimal clinical important difference between baseline and 12 months for all domains but showed some decline at 24 months. CONCLUSION: An intra-gastric balloon as an adjunct to a lifestyle support programme represents a safe and well tolerated treatment approach in severely obese adolescents, with short-term effects on weight change. Improvements in psychosocial health, physical activity and cardiorespiratory fitness were maintained at 12 months, with varying results at 24 months

Rotational knee laxity: Reliability of a simple measurement device in vivo

<p>Abstract</p> <p>Background</p> <p>Double bundle ACL reconstruction has been demonstrated to decrease rotational knee laxity. However, there is no simple, commercially-available device to measure knee rotation. The investigators developed a simple, non-invasive device to measure knee rotation. In conjunction with a rigid boot to rotate the tibia and a force/moment sensor to allow precise determination of torque about the knee, a magnetic tracking system measures the axial rotation of the tibia with respect to the femur. This device has been shown to have acceptable levels of test re-test reliability to measure knee rotation in cadaveric knees.</p> <p>Methods</p> <p>The objective of this study was to determine reliability of the device in measuring knee rotation of human subjects. Specifically, the intra-tester reliability within a single testing session, test-retest reliability between two testing sessions, and inter-tester reliability were assessed for 11 male subjects with normal knees.</p> <p>Results</p> <p>The 95% confidence interval for rotation was less than 5° for intra-tester, test-retest, and inter-tester reliability, and the standard error of measurement for the differences between left and right knees was found to be less than 3°.</p> <p>Conclusion</p> <p>It was found that the knee rotation measurements obtained with this device have acceptable limits of reliability for clinical use and interpretation.</p

Applying the multi-threat framework of stereotype threat in the context of digital gaming.

Females often report experiencing stigmatisation pertaining to their competency in digital gaming communities. Employing the principles of the multi-Threat framework of stereotype threat, the current research examined the impact of gender-related stereotypes on females' gaming performance and related self-perceptions. In Experiment 1, 90 females were assigned to one of three conditions in which they were primed that their performance would be either diagnostic of their personal (self-As-Target) or gender group's ability (group-As-Target) or would be non-diagnostic of gaming ability (control). In Experiment 2, 90 females were primed that their performance would be judged by a group of other females (in-group source) or males (out-group source), or would be non-diagnostic of ability (control). Participants then completed a casual gaming task, as well as measures of competence beliefs, self-efficacy and self-esteem. Findings from Experiment 1 indicate that neither a self-As-Target nor a group-As-Target stereotype affected significantly gaming performance, or gamerelated self-efficacy, self-esteem and competency beliefs. Findings from Experiment 2 reveal further that females' gaming performance and associated self-perceptions were not impacted significantly by an in-group or out-group source of stereotype threat. The discussion turns to potential explanations for these findings, proposing that females may not perceive negative gender-gaming stereotypes to be an accurate representation of their personal or social group's gaming ability. We also discuss the implications of the experimental design and difficulty, as well as the potential for domain identification to moderate performance outcomes under stereotype threat

Self-esteem is associated with premorbid adjustment and positive psychotic symptoms in early psychosis

<p>Abstract</p> <p>Background</p> <p>Low levels of self-esteem have been implicated as both a cause and a consequence of severe mental disorders. The main aims of the study were to examine whether premorbid adjustment has an impact on the subject's self-esteem, and whether lowered self-esteem contributes to the development of delusions and hallucinations.</p> <p>Method</p> <p>A total of 113 patients from the Thematically Organized Psychosis research study (TOP) were included at first treatment. The Positive and Negative Syndrome Scale (PANSS) was used to assess present symptoms. Premorbid adjustment was measured with the Premorbid Adjustment Scale (PAS) and self-esteem by the Rosenberg Self-Esteem Scale (RSES).</p> <p>Results</p> <p>Premorbid social adjustment was significantly related to lower self-esteem and explained a significant proportion of the variance in self-esteem. Self-esteem was significantly associated with the levels of persecutory delusions and hallucinations experienced by the patient and explained a significant proportion of the variance even after adjusting for premorbid functioning and depression.</p> <p>Conclusion</p> <p>There are reasons to suspect that premorbid functioning is an important aspect in the development of self- esteem, and, furthermore, that self-esteem is associated with the development of delusions and hallucinations.</p

Human Induced Pluripotent Stem Cells Differentiation into Oligodendrocyte Progenitors and Transplantation in a Rat Model of Optic Chiasm Demyelination

BACKGROUND: This study aims to differentiate human induced pluripotent stem cells (hiPSCs) into oligodendrocyte precursors and assess their recovery potential in a demyelinated optic chiasm model in rats. METHODOLOGY/PRINCIPAL FINDINGS: We generated a cell population of oligodendrocyte progenitors from hiPSCs by using embryoid body formation in a defined medium supplemented with a combination of factors, positive selection and mechanical enrichment. Real-time polymerase chain reaction and immunofluorescence analyses showed that stage-specific markers, Olig2, Sox10, NG2, PDGFRα, O4, A2B5, GalC, and MBP were expressed following the differentiation procedure, and enrichment of the oligodendrocyte lineage. These results are comparable with the expression of stage-specific markers in human embryonic stem cell-derived oligodendrocyte lineage cells. Transplantation of hiPSC-derived oligodendrocyte progenitors into the lysolecithin-induced demyelinated optic chiasm of the rat model resulted in recovery from symptoms, and integration and differentiation into oligodendrocytes were detected by immunohistofluorescence staining against PLP and MBP, and measurements of the visual evoked potentials. CONCLUSIONS/SIGNIFICANCE: These results showed that oligodendrocyte progenitors generated efficiently from hiPSCs can be used in future biomedical studies once safety issues have been overcome