Mechanisms of Neutrophil Recruitment and Immunopathology During Acute Clostridium difficile Colitis.

C. difficile infection in mice is associated with acute colitis characterized by the induction of inflammatory cytokines, intestinal histopathology, and robust neutrophil recruitment. Our objective was to determine the roles of the inflammatory cytokines GM-CSF, TNFa, IL-23, IL-22, and IL-17a in promoting neutrophil recruitment and innate inflammation in response to C. difficile infection. Ablation of GM-CSF signaling in vivo using a depleting anti-GM-CSF mAb was associated with significant reduction in colonic expression of Il1b, Tnfa, and Inos. Furthermore, expression of the neutrophil chemotactic factors Cxcl1 and Cxcl2 was also reduced in the colonic mucosa of anti-GM-CSF treated mice. Notably, anti-GM-CSF treatment did not affect intestinal histopathology. Direct reduction in neutrophil recruitment through the use of a depleting anti-Gr-1 antibody was not associated with reduction in the host inflammatory response. Colonic expression of inflammatory cytokines, including Tnfa, Il6, and Il33, and the neutrophil chemotactic factors Cxcl1 and Cxcl2 was unchanged following anti-Gr-1 treatment. Furthermore, colonic histopathology was no attenuated in anti-Gr-1 treated mice. Ablation of TNFa signaling was associated with increased inflammatory cytokine expression. While anti-TNFa treatment did not reduced neutrophil recruitment or expression of Cxcl1 and Cxcl2, the expression of numerous inflammatory cytokines including Il1b and Il6 were increased in anti TNFa-treated mice. Additionally, anti-TNFa treatment was associated with the development of more severe colonic histopathology following C. difficile infection. IL-23 deficiency was associated with significantly decreased neutrophil recruitment. Concomitant with the reduced neutrophilic influx, the expression of the neutrophil-recruiting chemokines Cxcl1, Cxcl2, and Ccl3 was also significantly reduced. IL-17 and IL-22 expression were also significantly reduced in the absence of IL-23, as was expression of the antimicrobial peptide RegIIIg. Furthermore, the induction of inflammatory cytokines including Tnfa, Il33, and Il6 was significantly reduced in IL-23-/- mice. Inflammatory cytokine expression and neutrophilic inflammation were not reduced in IL-17a-deficient mice or in mice treated with anti-IL-22 depleting mAb. However, RegIIIg expression was significantly reduced in anti-IL-22 treated animals. Taken together these data suggest that IL-23 and GM-CSF, independent of IL-17a, IL-22, and TNFa, drive neutrophil recruitment and inflammatoryPHDMicrobiology and ImmunologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/113375/1/mcderand_1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/113375/2/mcderand_3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/113375/3/mcderand_2.pd

What benefits does team sport hold for the workplace? A systematic review

Physical inactivity is proven to be a risk factor for non-communicable diseases and all-cost mortality. Public health policy recommends community settings worldwide such as the workplace to promote physical activity. Despite the growing prevalence of workplace team sports, studies have not synthesised their benefits within the workplace. A systematic review was carried out to identify articles related to workplace team sports, including intervention, observational and qualitative studies. Eighteen studies met the inclusion criteria. The findings suggest team sport holds benefits not only for individual health but also for group cohesion and performance and organisational benefits such as the increased work performance. However, it is unclear how sport is most associated with these benefits as most of the studies included poorly described samples and unclear sports activities. Our review highlights the need to explore and empirically understand the benefits of workplace team sport for individual, group and organisational health outcomes. Researches carried out in this field must provide details regarding their respective samples, the sports profile and utilise objective measures (e.g., sickness absence register data, accelerometer data)

Pilot Investigation into the Use of an Anthropomorphic Breast Sonography Phantom as a Training and Assessment Tool

A device for the training and quantitative assessment of the competency of trainee radiologists in the technically challenging area of breast sonography was developed and evaluated. Currently, suitable commercially available devices are lacking, and there is a growing realization that the reliance on direct exposure to patients for learning may not represent best practice from either the trainees\u27 or patients\u27 perspective. Three devices (PI, PII and PIII) were designed to produce very realistic sonographic images of breast morphology with a range of embedded pathologies. The pilot evaluation used a case study research design to evaluate the role of the anthropomorphic breast sonography training device in training and assessment in a clinical environment. Through the case study, it was possible to evaluate the process and relationships when using this type of training intervention for a small group of radiology resident trainees. The investigation involved a baseline assessment of trainees\u27 (n = 4) ability to detect and characterize all lesions in PI, followed by a 4-wk training period on PII and a post-training assessment using PIII. The evaluation revealed an improvement of 30% ± 8% in the trainee\u27s performance from pre- to post-training. It was expected that the performance of the trainees would improve as the training phantom described in this study aligns with the learning theory of constructivism and fits the ideal specifications of a medical training device in terms of its realism and facilitation of self-directed learning and deliberate practice of the trainees. The device provides a useful platform upon which training and assessment can be facilitated

What are the facilitators and obstacles to participation in workplace team sport? A qualitative study

Working age adults are failing to meet physical activity recommendations. Inactive behaviours are increasing costs for diminished individual and organisational health. The workplace is a priority setting to promote physical activity, however there is a lack of evidence about why some employees choose to participate in novel workplace activities, such as team sport, whilst others do not. The aim of this study was to explore the complexity of facilitators and obstacles associated with participation in workplace team sport. Twenty-nine semi-structured face-to-face and telephone interviews were conducted with office workers (58% female) (36 ± 7.71) from manufacturing, public services, and educational services. Data was analysed through template analysis. Five sub-level (i.e., intrapersonal, interpersonal, organisational, community and societal influences) facilitate participation or create obstacles for participants. Participants were challenged by a lack of competence, self-efficacy, negative sporting ideals and amotivation. Unhealthy competition, an unstable work-life balance and unsupportive colleagues created obstacles to participation. An unsupportive organisation and workplace culture placed demands on workplace champions, funding, facilities and communication. Healthy competitions, high perceptions of competence and self-efficacy, and being motivated autonomously enabled participation. Further, relatedness and social support created a physical activity culture where flexible working was encouraged and team sport was promoted in accessible locations within the organisation. Researchers should consider accounting for complexity of these influences. A participatory approach may tailor interventions to individual organisations and the employees that work within them. Interventions whereby autonomy, competence and relatedness are supported are recommended. This may be achieved by adapting sports and training workplace champions

It's time to start changing the game: A 12-week workplace team sport intervention study

Background A 12-week multi-team sport programme was provided to employees of a large services organisation and conducted in workplaces. This programme was used to investigate the short-term effect of regular sports team participation on individual employee and organisational health. Methods A large services organisation participated in this study. Two regional worksites of office workers were assigned as the team sport (intervention) (n = 28 participants) or control (n = 20 participants) groups. The team sport sessions were underpinned by psychological behaviour change theory and consisted of weekly 1-h team sport sessions for 12 weeks. Measures of aerobic fitness, physical activity behaviour, group cohesion, interaction and communication, psychological wellbeing, health, anthropometrics and workplace experiences were recorded pre- and post-intervention. Data were analysed using a series of mixed ANOVAs. Results After 12 weeks significant improvements were observed in VO2 max (+ 4.5 ± 5.8 ml/min kg, P < .002, η 2 p = .182), interpersonal communication within teams (+ 3%, P < .042, η 2 p = .087) and mean weekly physical activity duration (+ 154.74′, P < .002, η 2 p = .071) in the intervention group. A significant (P < .012, η 2 p = .130) effect on body composition was observed in the intervention group. Conclusions Participation in team sport may be an effective method to improve the aerobic fitness and physical activity behaviour of employees, and promote interpersonal communication between colleagues. Individual health outcomes and social interactions have the capacity to influence the health of the organisation. The extent of which these findings are replicable across a scope of organisations should be examined objectively over the long term

Building an Online Learning Community for Technology Integration in Education

Our professional learning community (PLC), or the Technology Integration Learning Community (TILC), consists of nine professors from the Fischler College of Education at Nova Southeastern University who embody a wide range of knowledge and skills related to instruction, research, and technology. Our TILC provides a supportive, collaborative, safe, and non-judgmental environment for sharing that knowledge (and questions) about technology tools and ideas that can be used to enhance both instruction and learning. Through a self-study, the TILC developed a framework for members to improve their own effectiveness when working with students enrolled in their courses at both the graduate and undergraduate levels

Molecular mechanisms underlying the effects of statins in the central nervous system

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly referred to as statins, are widely used in the treatment of dyslipidaemia, in addition to providing primary and secondary prevention against cardiovascular disease and stroke. Statins’ effects on the central nervous system (CNS), particularly on cognition and neurological disorders such as stroke and multiple sclerosis, have received increasing attention in recent years, both within the scientific community and in the media. Current understanding of statins’ effects is limited by a lack of mechanism-based studies, as well as the assumption that all statins have the same pharmacological effect in the central nervous system. This review aims to provide an updated discussion on the molecular mechanisms contributing to statins’ possible effects on cognitive function, neurodegenerative disease, and various neurological disorders such as stroke, epilepsy, depression and CNS cancers. Additionally, the pharmacokinetic differences between statins and how these may result in statin-specific neurological effects are also discussed

Role of interferon‐γ and inflammatory monocytes in driving colonic inflammation during acute Clostridium difficile infection in mice

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136491/1/imm12700.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136491/2/imm12700_am.pd

Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Tobacco use is the main risk factor for HNSCC, and tobacco-associated HNSCCs have poor prognosis and response to available treatments. Recently approved anti-PD-1 immune checkpoint inhibitors showed limited activity (≤20%) in HNSCC, highlighting the need to identify new therapeutic options. For this, mouse models that accurately mimic the complexity of the HNSCC mutational landscape and tumor immune environment are urgently needed. Here, we report a mouse HNSCC model system that recapitulates the human tobacco-related HNSCC mutanome, in which tumors grow when implanted in the tongue of immunocompetent mice. These HNSCC lesions have similar immune infiltration and response rates to anti-PD-1 (≤20%) immunotherapy as human HNSCCs. Remarkably, we find that &gt;70% of HNSCC lesions respond to intratumoral anti-CTLA-4. This syngeneic HNSCC mouse model provides a platform to accelerate the development of immunotherapeutic options for HNSCC