Direct interaction between cholera toxin and dendritic cells is required for oral adjuvant activity

Cholera toxin (CT) binds to GM1‐ganglioside receptors present on all nucleated cells. Despite this, it is a very potent mucosal adjuvant that has a dramatic impact on immune cells, as well as nerve and epithelial cells, causing diarrhea. This fact has hampered our understanding of whether the adjuvanticity of CT is direct or indirect, as cells that bind CT may or may not be involved in its adjuvant function. The mucosal barrier is maintained by tight junctions between epithelial cells but dendritic cells (DCs) can protrude luminal dendrites. Here we investigated which cells are involved in the immune augmenting effect of CT. We explored oral immunizations with ovalbumin (OVA) and CT in bone marrow chimeric mice deficient in GM1‐ganglioside in defined cellular subsets. We found that chimeric mice lacking GM1 in nonhematopoietic cells, including epithelial cells, mounted an unaltered intestinal IgA response. In contrast, chimeric mice lacking GM1‐expressing hematopoietic cells in general, or specifically GM1‐expressing conventional DCs (cDCs), largely failed to elicit anti‐OVA adaptive immune responses. Therefore, the adjuvanticity of CT does not require epithelial activation, but is directly dependent on the binding of CT to gut cDCs via GM1‐ganglioside. These results could have important implications for the generation of novel oral adjuvants.     

Lateral biases in lighting of abstract artwork

Previous studies examining perceptual biases in art have revealed that paintings tend to be lit from above and to the left. Abstract images provide a way of testing for the left-light bias while controlling for cues such as posing biases, ground line, shadows, and reflections. A total of 42 participants completed a task that required moving a “virtual flashlight” across the surface of abstract images presented on a computer screen: 20 images (presented both right-side-up and upside down) were used in the study. The participant's only instruction was to “light the painting in a way that is most aesthetically pleasing to you”. As predicted, participants on average focused the “virtual flashlight” in the top left quadrant. This study reveals that lateral lighting biases in artwork are not dependent on perception of local light source or interactions with discrete, concrete visual representations in the artwork.     

Introducing case management for people with dementia in primary care: a mixed-methods study

Background

Case management may be a feasible solution to the problem of service fragmentation for people with dementia.

Aim

To adapt a US model of primary care-based case management for people with dementia and test it in general practice.

Design and setting

Mixed-methodology case studies of case management implementation in four general practices: one rural, one inner-city, and two urban practices. Practice nurses undertook the case manager role in the rural and inner-city practices, and were allocated one session per week for case management by their practices. A seconded social worker worked full time for the two urban practices.

Method

Participants were community-dwelling patients with dementia who were living at home with a family carer, and who were not receiving specialist care coordination. Case study methods included analysis of case loads and interviews with patients, carers, local NHS and other stakeholders, and case managers. Measures included numbers of patients with dementia and their carers, number of unmet needs identified, and actions taken to meet needs. Case manager records were compared with findings from interviews with patients and carers, and with other stakeholders.

Results

The number of eligible patients was smaller than expected. No practice achieved its recruitment target. Researchers identified more unmet needs than case managers. The practice nurse case managers reported lack of time and found research documentation burdensome. Patients and carers were positive about case management as a first point of contact with the practice, as a ‘safety net’, and for creating a one-to-one therapeutic relationship.

Conclusion

Further investigation is required before case management for people with dementia and their carers can be implemented in primary care.     

Should prophylactic antibiotics be used routinely in epistaxis patients with nasal packs?

Introduction

The current mainstream practice in otolaryngology departments relating to the use of prophylactic antibiotics in epistaxis patients requiring nasal packing is highly variable. This is due primarily to the lack of any validated guidelines. As such, we introduced a new treatment algorithm resulting in significant reduction of use in the systemic antibiotics, with emphasis instead on the use of topical antibiotics. The results were validated through a complete audit cycle.

Methods

A total of 57 patients undergoing nasal packing for spontaneous epistaxis were studied. Reaudit occurred after the implementation of new guidelines. Telephone surveys were conducted six weeks after hospital discharge, assessing infective nasal symptoms as well as rebleeding and readmission rates.

Results

Systemic antibiotic prescribing in anterior nasal packing fell by 58.2% between audit cycles with no statistically significant associated increase in infective nasal symptoms, rebleeding or readmission rates six weeks following hospital discharge.

Conclusions

Systemic prophylactic antibiotics are unnecessary in the majority of epistaxis patients with nasal packs. The use of topical antibiotics such as Naseptin^® may be more appropriate, cheaper and as effective. Implementation of this treatment algorithm will help standardise systemic antibiotic usage in epistaxis patients with nasal packing and should reduce costs associated with unnecessary use of such medication.     

Reconstruction of perineal defects

Introduction

Perineal defects are commonly encountered in an oncological setting although they may also present as a result of trauma and infection (eg following Fournier’s gangrene). Reconstruction of these poses functional as well as aesthetic challenges. Skin coverage and tissue volume may both be required in addition to anogenital preservation or reconstruction. General prerequisites of an adequate reconstruction of perineal defects include provision of skin cover, well vascularised tissue to fill the dead space (reducing fluid collection and infection), vulvovaginal reconstruction and no faecal or urinary contamination.

Methods

A literature search was performed using PubMed and MEDLINE^®. The search terms included ‘perineal defects’, ‘perineal reconstruction’, ‘perforator flaps for perineum’, ‘vulval flaps’, ‘secondary healing of wound’ and ‘vacuum assisted closure’. Backward chaining of reference lists from retrieved papers was also used to expand the search.

Findings

Modern developments have led to an increased expectation in improved quality of life as the main goal of reconstruction, therefore necessitating surgery with less morbidity and early return to normal activity. Progress in microsurgical procedures has been the main recent advance in perineal reconstruction and, in future, refinements in perforator flap design and tissue engineering techniques will lead to even better reconstructions.     

A review of outcomes of the surgical management of femoroacetabular impingement

Introduction

Femoroacetabular impingement (FAI) resulting from abnormal contact between the acetabulum and femur has been studied extensively in recent years owing to its association with acetabular labrum tears and possible contribution to the development of osteoarthritis.

Methods

A comprehensive PubMed, MEDLINE^® and Embase™ literature search was conducted. Search terms included ‘femoroacetabular impingement’, ‘pathophysiology’, ‘diagnosis’, ‘dGEMRIC’, ‘arthroscopic’, ‘open’, ‘mini-open’ and ‘outcome measure’.

Results

A range of radiographic features have been described, and computed tomography and magnetic resonance imaging are both commonly used in the diagnosis of the bony abnormalities in FAI. Treatment of FAI is surgical with methods of treatment ranging from open surgical hip dislocation to arthroscopic osteochondroplasty.

Conclusions

In recent years, a trend towards the use of arthroscopic treatment for FAI has been seen, with promising results from a range of studies. However, only short-term outcome data are available and a range of different outcome measures have been used in studies to date. We present an overview of the outcomes for a range of surgical treatment methods for FAI and discuss the outcome measures used.