Is being a victim of bullying or cyberbullying in secondary school associated with subsequent risk-taking behavior in adolescence? A longitudinal study in secondary schools.

INTRODUCTION: Neurobiological and social changes in adolescence can make victims of bullying more susceptible to subsequent impulsive behavior. With the high prevalence of bullying in schools and rise in cyberbullying in the United Kingdom, it is important that the health impacts of bullying victimization, including on risk-taking, are understood. Our study aims to investigate whether bullying/cyberbullying victimization is associated with subsequent health risk-taking behavior in adolescence. Risk-taking behavior includes electronic cigarette and cigarette smoking, alcohol consumption, illicit drug use, early sexual debut, weapon carrying, damaging property, and setting fire. METHODS: A secondary quantitative analysis of data from 3337, English, secondary school students in the control arm of the INCLUSIVE trial, constituting an observational cohort. Bullying victimization was measured at baseline (age 11/12 years) using the gatehouse bullying scale and a separate question on cyberbullying victimization. Logistic regression was used to test for an association between bullying/cyberbullying victimization at baseline and risk-taking behavior at 36 months, adjusting for baseline risk-taking behavior and other potential confounders, and accounting for school clustering. RESULTS: There was strong evidence (p ≤ .02) for a positive dose-responsive association between being bullied at baseline and nearly all risk-taking behavior at follow-up. Although there was no evidence for an association between being bullied at baseline and weapon carrying (p = .102), there was evidence for a positive association between being cyberbullied at baseline and weapon carrying (p = .036). CONCLUSIONS: It is plausible that bullying/cyberbullying victimization increases the likelihood of subsequent risk-taking behavior in adolescence. Policy options should focus on implementing evidence-based antibullying school interventions.

Synovial chondromatosis of the temporomandibular joint with extension into the middle cranial fossa and internal carotid canal.

This report presents the case of an extensive synovial chondromatosis of the temporomandibular joint (TMJ), with extension into the middle cranial fossa, middle ear, and carotid canal. Synovial chondromatosis of the TMJ is rare, particularly when associated with intracranial involvement. This case is unique owing to its size and the involvement with the internal carotid artery. The importance of a multidisciplinary approach in the surgical management of such a rare and complex form of this condition is highlighted.

The minimal leak test technique for endotracheal cuff maintenance.

Endotracheal tube (ETT) cuff pressure management is an essential part of airway management in intubated and mechanically ventilated patients. Both under- and over-inflation of the ETT cuff can lead to patient complications, with an ideal pressure range of 20-30 cmH2O defined. A range of techniques are employed to ensure adequate ETT cuff inflation, with little comparative data. We performed an observational cross-sectional study in a tertiary metropolitan ICU, assessing the relationship between the minimal leak test and cuff manometry. Forty-five mechanically ventilated patients, over a three-month period, had ETT cuff manometry performed at the same time as their routine cuff maintenance (minimal leak test). Bedside nurse measurements were compared with investigator measurements. At the endpoint of cuff inflation, 20 of 45 patients (44%) had cuff pressures between 20 and 30 cmH2O; 11 of 45 patients (24%) had cuff pressures <20 cmH2O; 14 of 45 patients (31%) had cuff pressures ≥30 cmH2O. Univariate analysis demonstrated an association between both patient obesity and female gender requiring less ETT cuff volume (P=0.008 and P <0.001 respectively), though this association was lost on multivariate analysis. No association was demonstrated between any measured variables and cuff pressures. Inter-operator reliability in performing the minimal leak test showed no evidence of bias between nurse and investigators (Pearson coefficient = 0.897). We conclude the minimal leak test for maintenance of ETT cuffs leads to both over- and under-inflation, and alternative techniques, such as cuff manometry, should be employed.

Elevated remnant lipoproteins may increase subclinical CVD risk in pre-pubertal children with obesity: a case-control study.

OBJECTIVES: Current clinical guidelines to assess paediatric cardiovascular disease (CVD) risk heavily rely on cholesterol parameters that are generally normal for obese children. Remnant lipoproteins have emerged as a critical CVD risk factor particularly in adults with normolipidemia. We assessed remnant lipoprotein concentration (measured by apolipoprotein [apo] B48) and its relationship with other traditional CVD risk biomarkers in pre-pubertal children with obesity. METHODS: Pre-pubertal children (n = 78) with obesity (n = 39, 9.9 ± 0.3 years old) as well as sex-matched normal-weight controls (n = 39, 9.8 ± 0.3 years) were assessed for anthropometry, blood pressure and fasting plasma biochemical parameters for remnant lipoprotein, lipid and glucose/insulin metabolism, and inflammatory status. RESULTS: Children with obesity had striking 2-fold higher apoB48-containing remnant lipoproteins concentrations relative to normal-weight peers; the magnitude of elevation in the remnant lipoproteins is comparable to the levels previously reported for adults with established CVD and type-2 diabetes. Fasting apoB48 was positively correlated with fasting triglyceride concentration in children with obesity (r = 0.51, P < 0.001) and their normal-weight peers (r = 0.45, P < 0.01). Traditional CVD biomarkers including low-density lipoprotein cholesterol showed no difference between groups and remained within the normal range for a paediatric population. CONCLUSION: Elevated apoB48-containing remnant lipoprotein is a stronger biomarker for paediatric CVD risk compared to traditional cholesterol parameters and may be associated with early adaptation of the intestine during obesity. Further investigation of abnormalities associated with the secretion and/or clearance of atherogenic remnant lipoproteins during the postprandial state may yield insight into our understanding of and therapeutic targets for managing risk for CVD in children with obesity.

The signs and symptoms of tooth wear in a referred group of patients.

AIM: To determine the prevalence of signs and symptoms in a group of tooth wear patients referred to a hospital-based consultant clinic. METHOD: The clinical records of 290 patients referred to the Liverpool University Dental Hospital for tooth wear were reviewed retrospectively. A systematic sampling technique was used to select every alternate patient held on the consultant database. RESULTS: There were significantly more males than females in a ratio of 2.3:1. Significantly more males (56%) presented with severe tooth wear compared with females (31%) (p <0.001). Aesthetic concerns were the most prevalent presenting complaint (59%) and sensitivity was the second most common presenting complaint (40%). Functional problems and pain were less prevalent at 17% and 14% respectively. Subjects who had lost posterior support had more severe wear and more worn anterior teeth, which was statistically significant (p = 0.001). The proportion of subjects with undiagnosed apical pathology on worn teeth was 13%. CONCLUSIONS: Tooth wear predominated in males in this study. Patient dissatisfaction with appearance is the most common complaint and endodontic signs and symptoms are low in prevalence. Contrary to previous studies, lack of posterior support resulted in greater severity of wear, therefore restoring support is recommended.

Surgical complications of segmental Le Fort I osteotomy.

Segmental maxillary osteotomy is a useful adjunct in orthognathic surgery for the correction of vertical and transverse maxillary deformities, but we know of few published reports that document complications. We evaluated the complication rates associated with segmental maxillary surgery in our unit by retrospective review of medical records, radiographs, and study models of 85 consecutive patients (mean age 23.3 years, range 14-51; male:female ratio 1:2) treated from 1995 to 2009. Types of deformity were anterior open bite (n=30, 35%), transverse maxillary deficiency (n=24, 28%), anterior open bite with transverse maxillary deficiency (n=28, 33%), and anterior vertical maxillary excess (n=3, 4%). There were 70 tripartite (82%), 13 bipartite (15%), and two quadripartite (2%) maxillas. Twenty-one patients (25%) had bone grafts. Fixation was done using titanium miniplates in 80 patients (94%), and titanium miniplates and resorbable plates in five (6%). The overall complication rate was 27%. Three patients (4%) had devitalisation of teeth, three (4%) developed minor periodontal defects, and one had tooth loss. Eight patients (9%) had plates removed, and two patients developed persistent postoperative palatal fistula. There was no segmental loss of bone or teeth. Our results show that complications in this cohort were relatively low, and that segmental maxillary surgery is safe as an adjunct in carefully selected cases.

The potential use of protein kinase D inhibitors for prevention/treatment of epidermal tumors.

BACKGROUND: The serine/threonine kinase protein kinase D (PKD) has been proposed to be a pro-proliferative, anti-differentiative signal in epidermal keratinocytes. Indeed, the phorbol ester tumor promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA) induces biphasic PKD activation, which mirrors the biphasic response of initial differentiation followed by proliferation and tumor promotion seen in TPA-treated keratinocytes in vitro and epidermis in vivo. OBJECTIVE: Our objective was to test the idea that PKD's pro-proliferative and/or anti-differentiative effects in keratinocytes contribute to TPA-induced tumorigenesis. METHODS: Using western analysis and assays of keratinocyte proliferation and differentiation, we investigated the effect of inhibitors of PKD on keratinocyte function. RESULTS: We found that overexpression of a constitutively active PKD mutant increased, and of a dominant-negative PKD mutant decreased, keratinocyte proliferation. A recently described selective PKD inhibitor showed low potency to inhibit keratinocyte proliferation or PKD activation. Therefore, we tested the ability of known only relatively selective PKD inhibitors on keratinocyte function and protein kinase activation. H89 {N-[2-(p-bromocinnamylamino) ethyl]-5-isoquinoline-sulfonamide}, a reported inhibitor of PKD and cAMP-dependent protein kinase, enhanced the effect of a differentiating agent on a marker of keratinocyte differentiation. Another reported non-selective PKD inhibitor, resveratrol stimulated differentiation and inhibited proliferation. The protein kinase C/PKD inhibitor Gö6976 blocked the increase in proliferation (as measured by DNA specific activity) induced by chronic TPA without affecting the initial TPA-elicited differentiation. CONCLUSION: Our results support the idea that relatively selective PKD inhibitors, such as Gö6976, H89 and resveratrol, might be useful for preventing/treating epidermal tumorigenesis without affecting keratinocyte differentiation.

Outcomes of revision total hip replacement for infection after grading according to a standard protocol.

Periprosthetic infection following total hip replacement can be a catastrophic complication for the patient. The treatments available include single-stage exchange, and two-stage exchange. We present a series of 50 consecutive patients with a diagnosis of infected total hip replacement who were assessed according to a standardised protocol. Of these, 11 underwent single-stage revision arthroplasty with no recurrence of infection at a mean of 6.8 years follow-up (5.5 to 8.8). The remaining 39 underwent two-stage revision, with two recurrences of infection successfully treated by a second two-stage procedure. At five years, significant differences were found in the mean Harris Hip Scores (single-stage 87.8; two-stage 75.5; p = 0.0003) and in a visual analogue score for satisfaction (8.6; 6.9; p = 0.001) between the single- and two-stage groups. Single-stage exchange is successful in eradicating periprosthetic infection and results in excellent functional and satisfaction scores. Identification of patients suitable for the single-stage procedure allows individualisation of care and provides as many as possible with the correct strategy in successfully tackling their periprosthetic infection.

The ENTH domain protein Clint1 is required for epidermal homeostasis in zebrafish.

Epidermal hyperproliferation and inflammation are hallmarks of the human condition psoriasis. Here, we report that a zebrafish line with a mutation in the cargo adaptor protein Clint1 exhibits psoriasis-like phenotypes including epithelial hyperproliferation and leukocyte infiltration. Clint1 is an ENTH domain-containing protein that binds SNARE proteins and functions in vesicle trafficking; however, its in vivo function in animal models has not been reported to date. The clint1 mutants exhibit chronic inflammation characterized by increased Interleukin 1beta expression, leukocyte infiltration, bidirectional trafficking and phagocytosis of cellular debris. The defects in clint1 mutants can be rescued by expression of zebrafish clint1 and can be phenocopied with clint1-specific morpholinos, supporting an essential role for Clint1 in epidermal development. Interaction studies suggest that Clint1 and Lethal giant larvae 2 function synergistically to regulate epidermal homeostasis. Accordingly, clint1 mutants show impaired hemidesmosome formation, loss of cell-cell contacts and increased motility suggestive of epithelial to mesenchymal transition. Taken together, our findings describe a novel function for the ENTH domain protein Clint1 in epidermal development and inflammation and suggest that its deficiency in zebrafish generates a phenotype that resembles the human condition psoriasis.

Characterization of zebrafish larval inflammatory macrophages.

Zebrafish have emerged as a powerful model system to study leukocyte recruitment and inflammation. Here we characterize the morphology and function of inflammatory macrophages in zebrafish larvae. These macrophages can be distinguished from neutrophils by immunolabeling of L-Plastin without MPO co-expression and by an elongated morphology. Live imaging of transgenic zMPO:GFP larvae demonstrate that GFP(lo) macrophages migrate to wounds by extension of thin pseudopods and carry out phagocytosis of tissue debris, and FACS analysis of leukocyte markers indicates expression of CSF1R in these macrophages. These findings identify distinct functional and morphological characteristics of inflammatory macrophages in zebrafish larvae.

Muscle degeneration and leukocyte infiltration caused by mutation of zebrafish Fad24.

Factor for adipocyte differentiation 24 (fad24) is a novel gene that has been implicated in adipocyte differentiation and DNA replication. In a screen for zebrafish mutants that have an abnormal tissue distribution of neutrophils, we identified an insertional allele of fad24, fad24hi1019. Homozygous fad24hi1019 larvae exhibit muscle degeneration accompanied by leukocyte infiltration. Muscle degeneration was extensive and included tissue apoptosis and disorganized, poorly striated muscle fibers. Blocking apoptosis using pan-caspase inhibitors resulted in decreased neutrophil recruitment into the body of the larva, suggesting a causative link between apoptosis and leukocyte infiltration. These findings suggest that zebrafish is a powerful genetic model system to address the interplay between muscle degeneration and leukocyte infiltration, and indicate that tissue apoptosis may contribute to neutrophil recruitment in some inflammatory states.

European validation of the Vancouver classification of periprosthetic proximal femoral fractures.

The Vancouver classification has been shown by its developers to be a valid and reliable method for categorising the configuration of periprosthetic proximal femoral fractures and for planning their management. We have re-validated this classification system independently using the radiographs of 30 patients with periprosthetic fractures. These were reviewed by six experienced consultant orthopaedic surgeons, six trainee surgeons and six medical students in order to assess intra- and interobserver reliability and reproducibility. Each observer read the radiographs on two separate occasions. The results were subjected to weighted kappa statistical analysis. The respective kappa values for interobserver agreement were 0.72 and 0.74 for consultants, 0.68 and 0.70 for trainees on the first and second readings of the radiographs and 0.61 for medical students. The intra-observer agreement for the consultants was 0.64 and 0.67, for the trainees 0.61 and 0.64, and for the medical students 0.59 and 0.60 for the first and second readings, respectively. The validity of the classification was studied by comparing the pre-operative radiological findings within B subgroups with the operative findings. This revealed agreement for 77% of these type-B fractures, with a kappa value of 0.67. Our data confirm the reliability and reproducibility of this classification system in a European setting and for inexperienced staff. This is a reliable system which can be used by non-experts, between centres and across continents.

QTc dispersion in patients referred for electroconvulsive therapy.

OBJECTIVE: To determine the presence of possible risk factors for arrhythmias during electroconvulsive therapy (ECT) by assessing QTc dispersion on the baseline electrocardiogram. METHOD: The pre-ECT electrocardiogram on 105 patients was examined, and QTc dispersion was calculated. This was correlated with presence or absence of cardiac conditions and various psychotropic medications being used by the patients. RESULTS: Neither age nor sex was associated with QTc dispersion. Presence of cardiac illness also was not associated with prolongation of QTc dispersion. None of the psychotropic medication classes, including atypical antipsychotics, were associated with prolongation of QTc dispersion either. CONCLUSION: In patients referred for ECT, baseline QTc dispersion does not correlate with presence of cardiac illness or concomitant psychotropic usage.

A novel solution for severe urinary incontinence in women with cystic fibrosis.

BACKGROUND: To explore whether Tension-free Vaginal Tape offers a solution for women with cystic fibrosis who suffer from severe stress incontinence. METHODS: Four adults with cystic fibrosis were formally assessed by gynaecological and urological specialists, prior to hospital admission for surgery. RESULTS: The procedure was tolerated well by all patients. In three, leakage ceased completely. The fourth patient experienced considerable improvement in symptoms. CONCLUSIONS: Tension-free Vaginal Tape is a safe, effective and worthwhile solution for stress incontinence in females with cystic fibrosis.

Successful treatment of cepacia syndrome with combination nebulised and intravenous antibiotic therapy.

We report the case of successful treatment of a 31-year-old lady with cystic fibrosis and an en-bloc liver-pancreas transplant, who developed cepacia syndrome on a background of chronic infection with the ET12 epidemic strain of Burkholderia cenocepacia. Combination therapy with nebulised and intravenous meropenem and tobramycin led to clinical improvement with a return to baseline function and complete resolution of the acute chest X-ray changes.

Finding consensus on the physiotherapy management of asymptomatic infants with cystic fibrosis.

BACKGROUND: Babies with cystic fibrosis diagnosed by neonatal screening often display no overt signs of respiratory disease. The role of traditional routine daily chest physiotherapy in this particular group of babies is unclear and has generated considerable international debate. There is currently no evidence addressing this issue and present circumstances preclude a rigorous trial in the UK. This study aimed to provide expert consensus regarding the physiotherapy management of asymptomatic infants with CF. METHOD: A Delphi consensus method was used to gather and refine expert opinions of senior paediatric physiotherapists in the UK. Agreement was sought on 16 statements reflecting aspects of physiotherapy management in 'asymptomatic' babies with cystic fibrosis. RESULTS: Twenty-five senior paediatric physiotherapists from Specialist CF Centres throughout the UK participated in the study. Consensus was high amongst the respondents for 15 of the 16 statements. One statement failed to reach consensus. This related to the question of not routinely initiating a daily chest physiotherapy regimen in apparently healthy babies. Due to the lack of consensus an amendment to this statement was made, to allow a more flexible approach, where physiotherapists would not be obliged to initiate routine daily treatment in asymptomatic babies with CF, if they felt other another approach was justified. CONCLUSION: There was high consensus of opinion amongst senior physiotherapists in the UK on most aspects of the physiotherapy management of babies with CF. Consensus could not be achieved on whether routine daily chest physiotherapy is necessary in 'asymptomatic' babies. An agreed amendment to the original statement allows professionals to modify or change traditional practice with the sanction of their senior colleagues. The results of this process will be used by the Association of Chartered Physiotherapists in Cystic Fibrosis to form the basis of national clinical guidelines.

Quantitative measurement of postural sway in mouse models of human neurodegenerative disease.

Detection of motor dysfunction in genetic mouse models of neurodegenerative disease requires reproducible, standardized and sensitive behavioral assays. We have utilized a center of pressure (CoP) assay in mice to quantify postural sway produced by genetic mutations that affect motor control centers of the brain. As a positive control for postural instability, wild type mice were injected with harmaline, a tremorigenic agent, and the average areas of the 95% confidence ellipse, which measures 95% of the CoP trajectory values recorded in a single trial, were measured. Ellipse area significantly increased in mice treated with increasing doses of harmaline and returned to control values after recovery. We also examined postural sway in mice expressing mutations that mimic frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) (T-279, P301L or P301L-nitric oxide synthase 2 (NOS2)(-/-) mice) and that demonstrate motor symptoms. These mice were then compared with a mouse model of Alzheimer's disease (APPSwDI mice) that demonstrates cognitive, but not motor deficits. T-279 and P301L-NOS2(-/-) mice demonstrated a significant increase in CoP ellipse area compared with appropriate wild type control mice or to mice expressing the P301L mutation alone. In contrast, postural instability was significantly reduced in APPSwDI mice that have cognitive deficits but do not have associated motor deficits. The CoP assay provides a simple, sensitive and quantitative tool to detect motor deficits resulting from postural abnormalities in mice and may be useful in understanding the underlying mechanisms of disease.

Live imaging of chronic inflammation caused by mutation of zebrafish Hai1.

The hallmark of chronic inflammation is the infiltration and persistence of leukocytes within inflamed tissue. Here, we describe the first zebrafish chronic inflammation mutant identified in an insertional mutagenesis screen for mutants that exhibit abnormal tissue distribution of neutrophils. We identified a mutant line with an insertion in the Hepatocyte growth factor activator inhibitor 1 gene (hai1; also known as Spint1) that showed accumulation of neutrophils in the fin. The mutant embryos exhibited inflammation in areas of epidermal hyperproliferation that was rescued by knock-down of the type II transmembrane serine protease Matriptase 1 (also known as St14), suggesting a novel role for Hai1-Matriptase 1 pathway in regulating inflammation. Using time-lapse microscopy of mutant embryos that express GFP from a neutrophil-specific promoter, we found that individual neutrophils in inflamed tissue displayed random motility characterized by periods of pausing alternating with periods of motility. During periods of persistent movement the cells were highly polarized, while the pausing modes were characterized by a loss of cell polarity. In contrast to responses to acute injury, neutrophils did not exhibit clear retrograde chemotaxis or resolution of inflammation in the mutant. These findings illustrate the utility of zebrafish as a new model system to study chronic inflammation and to visualize immune responses with high resolution in vivo.

QTc dispersion on the baseline ECG predicts arrhythmias during electroconvulsive therapy.

OBJECTIVE: Our objective in this study was to test the hypothesis that prolonged QTc dispersion predisposes to arrhythmias in electroconvulsive therapy (ECT). METHODS AND RESULTS: We measured QTc dispersion on ECT patients' baseline ECG and also measured PVCs and PACs during and for two minutes after ECT seizures. Using Poisson regression analysis, we found that baseline QTc dispersion was positively associated with ictal and post ictal PVCs and with post ictal PACs. CONCLUSIONS: We conclude that QTc dispersion appears to be a valid predictor of arrhythmias.