Signal transducer and activator of transcription-3 licenses Toll-like receptor 4-dependent interleukin (IL)-6 and IL-8 production via IL-6 receptor-positive feedback in endometrial cells.

Interleukin 6 (IL-6), acting via the IL-6 receptor (IL6R) and signal transducer and activator of transcription-3 (STAT3), limits neutrophil recruitment once bacterial infections are resolved. Bovine endometritis is an exemplar mucosal disease, characterized by sustained neutrophil infiltration and elevated IL-6 and IL-8, a neutrophil chemoattractant, following postpartum Gram-negative bacterial infection. The present study examined the impact of the IL6R/STAT3 signaling pathway on IL-8 production by primary endometrial cells in response to short- or long-term exposure to lipopolysaccharide (LPS) from Gram-negative bacteria. Tyrosine phosphorylation of STAT3 is required for DNA binding and expression of specific targets genes. Immunoblotting indicated constitutive tyrosine phosphorylation of STAT3 in endometrial cells was impeded by acute exposure to LPS. After 24 h exposure to LPS, STAT3 returned to a tyrosine phosphorylated state, indicating cross-talk between the Toll-like receptor 4 (TLR4) and the IL6R/STAT3 signaling pathways. This was confirmed by short interfering RNA targeting the IL6R, which abrogated the accumulation of IL-6 and IL-8, induced by LPS. Furthermore, there was a differential endometrial cell response, as the accumulation of IL-6 and IL-8 was dependent on STAT3, suppressor of cytokine signaling 3, and Src kinase signaling in stromal cells, but not epithelial cells. In conclusion, positive feedback through the IL6R amplifies LPS-induced IL-6 and IL-8 production in the endometrium. These findings provide a mechanistic insight into how elevated IL-6 concentrations in the postpartum endometrium during bacterial infection leads to marked and sustained neutrophil infiltration.

Beta-papillomaviruses and psoriasis: an intra-patient comparison of human papillomavirus carriage in skin and hair.

BACKGROUND: Human papillomaviruses (HPVs) of the beta genus (beta-PV), especially HPV5 and HPV36, are proposed to play a pathogenic role in psoriasis, but many previous studies have failed to control for potential confounders, including treatment. OBJECTIVES: To re-examine the relationship between beta-PV and psoriasis addressing limitations present in previous studies and analyse intra-patient concordance for carriage of HPV. METHODS: Plucked eyebrow hairs and forearm skin scrapes were collected from 20 newly diagnosed, previously untreated adult patients with psoriasis and 23 normal controls. A combination of type-specific and degenerate polymerase chain reaction methods was used to achieve comprehensive HPV DNA detection. RESULTS: The prevalence of HPV in hair and skin from psoriasis patients was higher than in controls (83.3% vs. 46.7%, respectively, P < 0.03 corrected for age and clustering). HPV5 or HPV36 were not over-represented. The profile of diverse beta-PV types was comparable in the two groups. Intra-patient concordance for HPV DNA at separate sites was high (P < 0.00001). CONCLUSIONS: Our data do not support a specific causal role for HPV5 or HPV36 in psoriasis, but suggest that psoriatic skin may be more permissive for viral presence than normal skin. High intra-patient concordance for specific HPV types at separate sites, together with the ubiquity of HPV DNA in normal human skin, suggests that an individual becomes colonized with a particular beta-PV profile presumably to the exclusion of other types. To what extent this HPV profile is then causal in the subsequent development of hyperproliferative skin disease is unknown.

Breach avoidance facilitator--managing the A&E 4-hour target.

This paper aims to explore the concept of the breach avoidance facilitator (BAF) within the Accident & Emergency (A&E) department. This is a role that has been introduced utilising Senior Nursing staff on a supernumerary basis to predominantly provide a trouble-shooting role to manage the A&E 4-hour target. The paper will explore the initial practical difficulties that were encountered during the introduction of the role. The associated benefits of the role including monitoring of the 4-hour target, co-ordination of resources, increased communication with a variety of staff members, and the completion of a real time electronic hand-over form will be explored. The paper will also discuss how the role will evolve to provide support and clinical supervision for junior and ancillary staff.

Rapid assessment and initial patient treatment team -- a way forward for emergency care.

As a consequence of the UK Department of Health drive to introduce the 4-h emergency care target acute trusts have attempted to initialize a myriad of programmes to improve the patients' experience in this sector. Changes to how patients are managed and the flow that they enter within the emergency care system have become a popular option. This paper seeks to explore the concept of the Rapid Assessment and Initial Patient Treatment team (RAPT) within the Accident and Emergency (A and E) environment. We intend to provide information for readers who may be considering introducing such teams. The paper will explore the initial practical difficulties that were encountered. We will explore associated benefits for the RAPT approach including improved teamwork, better communication with the family, avoiding unnecessary duplication of work and discuss the benefits of having a direct referral process in place for emergency patients.

The introduction of the Manchester triage scale to an emergency department in the Republic of Ireland.

Triage is an integral part of the modern emergency department. The use of a recognised triage system has many advantages for the emergency department including reference to a recognised decision-making structure and support in the form of a professionally accepted and validated system. As part of a programme of internal change the Manchester triage system (MTS) was introduced to an emergency department in the Republic of Ireland. This article outlines the introduction of this method of triage and cites the domestic and international drivers of the change.