JunB as a potential mediator of PTHrP actions: new gene targets Ephrin B1 and VCAM‐1

Parathyroid hormone‐related protein (PTHrP) is an integral mediator of physiologic and pathologic processes and has demonstrated actions in the periodontium. PTHrP functions via AP‐1, and specifically through JunB. This study identified JunB‐dependent downstream mediators of PTHrP using OCCM cementoblastic transfectants with JunB over‐ or reduced expression. Over‐expressing cells showed an increase in proliferation, while the opposite was seen in siRNA transfected cells. Microarray analysis of over‐expressing cells revealed more than 1000 regulated genes. Three genes were investigated in more detail. The PTH/PTHrP receptor (PTHR1) and ephrin B1 (EfnB1) were down‐regulated, and vascular cell adhesion molecule‐1 (VCAM‐1) was up‐regulated with JunB over‐expression. JunB siRNA transfectants had increased PTHR1, but reduced ephrin B1 and unaltered VCAM‐1 in vitro. To validate these targets, parental OCCM cells and primary osteoblasts were treated with PTHrP, resulting in reduced PTHR1 and ephrin B1, and increased VCAM‐1. Cell transfectants were implanted subcutaneously in vivo, and microarray analysis and RT‐PCR performed. Over‐expression of JunB down‐regulated PTHR1 and ephrin B1, and increased VCAM‐1. JunB siRNA transfectant implants had increased PTHR1 and ephrin B1, but no altered VCAM‐1. These data highlight new gene targets for PTHrP and indicate JunB is a critical mediator of PTHrP actions.     

The rising rate of admissions for tonsillitis and neck space abscesses in England, 1991–2011

Introduction

Sore throats and tonsillitis represent a considerable health burden as well as a significant source of expenditure for the National Health Service (NHS). As part of the recent NHS savings drive, the introduction of ‘procedures of low clinical effectiveness’ (PoLCE) lists has reinforced a large reduction in the number of tonsillectomies performed. We carried out a cross-sectional study of trends in emergency sore throat admissions in the context of the number of tonsillectomies performed.

Methods

Hospital Episode Statistics (HES) data were extracted. Office for National Statistics data were also used.

Results

Between 1991 and 2011, the overall tonsillectomy rate fell by 44%. In the same time, the admission rate for tonsillitis rose by 310% (Pearson’s r=–0.67, p=0.01). The peritonsillar abscess admission rate rose by 31% (r=–0.79, p<0.01). Between 1996 and 2011, the overall tonsillectomy rate fell by 41% and the retro and parapharyngeal abscess admission rate rose by 39% (r=–0.55, p=0.026). There was a 14% overall increase in tonsillectomy and sore throat associated bed days. This was despite the large fall in tonsillectomy numbers and the reduction in length of hospital stay.

Conclusions

Efforts to reduce the tonsillectomy rate are correlated with a significant rise in emergency admissions. The rise in the retro and parapharyngeal abscess rate is perhaps most alarming given the very high mortality of these conditions. Bed day data suggest that no net saving has been made despite the new measures.     

Fall prediction using decision tree analysis in acute care units

[Purpose] To present an accurate and straight-forward system of fall prediction by performing decision tree analysis using both the fall assessment sheet and Berg balance scale (BBS). [Participants and Methods] The participants in this retrospective study were inpatients from acute care units. We extracted the risk factors for falls from the fall assessment and performed a decision tree analysis using the extracted fall risk factors and BBS score. [Results] “History of more than one fall in the last 1 year”, “Muscle weakness”, “Use of a walking aid or wheelchair”, “Requires assistance for transfer”, “Use of Narcotics”, “Dangerous behavior”, and “High degree of self-reliance” were fall risk factors. The decision tree analysis extracted five fall risk factors, with an area under the curve of 0.7919. Patients with no history of falls and who did not require assistance for transfer or those with a BBS score ≥51 did not fall. [Conclusion] Decision tree-based fall prediction was useful and straightforward and revealed that patients with no history of falling and those who did not require assistance for transfer or had a BBS score ≥51 had a low risk of falling.Key words: Falling, Balance, Decision tree     

Screening for vancomycin‐resistant enterococci: results of a survey in Stockholm

Fang H, Nord CE, Ullberg M. Screening for vancomycin‐resistant enterococci: results of a survey in Stockholm. APMIS 2010; 118: 413–7. Vancomycin‐resistant enterococci (VRE) are emerging in Stockholm hospitals. To rapidly screen for VRE from stool and rectal swab samples, a detection assay combining broth enrichment and real‐time PCR was set up. From September to December 2008, 6914 samples were screened for VRE using the broth‐PCR combined assay. Of them, 5463 samples were reported as negative the day after sampling. Among the 6914 samples, 47 was screened as vanA probable and 44 of them were confirmed as VRE; 1314 samples was screened as vanB probable and 93 of them were confirmed as VRE. The 44 vanA‐type VRE isolates, detected from 31 patients, were clustered into four genetic types by pulsed‐field gel electrophoresis (PFGE). The same PFGE type was observed in multiple isolates recovered from the same patient with vanA VRE. The 93 vanB‐type VRE isolates were detected from 60 patients, 59 of them harboring VRE with PFGE type 1. One patient with vanB VRE had two isolates of distinct PFGE types (types 1 and 5). PFGE type 1 and PFGE type 2 were predominant clones in vanB and vanA strains, respectively, represented by 98.3% (59/60) of patients with vanB VRE and 77.4% (24/31) of patients with vanA VRE.     

Reversal of Paralysis and Reduced Inflammation from Peripheral Administration of β-Amyloid in TH1 and TH17 Versions of Experimental Autoimmune Encephalomyelitis

β-Amyloid 42 (Aβ42) and β-amyloid 40 (Aβ40), major components of senile plaque deposits in Alzheimer's disease, are considered neurotoxic and proinflammatory. In multiple sclerosis, Aβ42 is up-regulated in brain lesions and damaged axons. We found, unexpectedly, that treatment with either Aβ42 or Aβ40 peptides reduced motor paralysis and brain inflammation in four different models of experimental autoimmune encephalomyelitis (EAE) with attenuation of motor paralysis, reduction of inflammatory lesions in the central nervous system (CNS), and suppression of lymphocyte activation. Aβ42 and Aβ40 treatments were effective in reducing ongoing paralysis induced with adoptive transfer of either autoreactive T helper 1 (T(H)1) or T(H)17 cells. High-dimensional 14-parameter flow cytometry of peripheral immune cell populations after in vivo Aβ42 and Aβ40 treatment revealed substantial modulations in the percentage of lymphoid and myeloid subsets during EAE. Major proinflammatory cytokines and chemokines were reduced in the blood after Aβ peptide treatment. Protection conferred by Aβ treatment did not require its delivery to the brain: Adoptive transfer with lymphocytes from donors treated with Aβ42 attenuated EAE in wild-type recipient mice, and Aβ deposition in the brain was not detected in treated EAE mice by immunohistochemical analysis. In contrast to the improvement in EAE with Aβ treatment, EAE was worse in mice with genetic deletion of the amyloid precursor protein. Therefore, in the absence of Aβ, there is exacerbated clinical EAE disease progression. Because Aβ42 and Aβ40 ameliorate experimental autoimmune inflammation targeting the CNS, we might now consider its potential anti-inflammatory role in other neuropathological conditions.