An Introduction to Periodical Bibliography (Book Review)

published or submitted for publicatio

Evaluation of an online youth ambassador program to promote mental health

To evaluate an online Youth Ambassador (YA) program designed to promote internet resources for mental health in an adolescent population, 56 YAs and 357 of their Year 10 peers from 11 Tasmanian schools completed e-mental health questionnaires before and after the YAs attended a single workshop session. The workshops, which were delivered in the high school setting, were either facilitated or self-directed. Self-reported awareness of e-mental health resources increased among both YAs and their peers. The peer group also showed increased frequency of recommending help-seeking to others. There were no differences in outcomes for facilitated or self-directed workshop formats. The results suggest that an online YA program delivered in school is useful in improving mental health awareness for workshop participants. While their Year 10 peer groups also showed increased awareness, this could not necessarily be attributed to the participation of all 11 schools in the YA program

School violence, school differences and school discourses

This article highlights one strand of a study which investigated the concept of the violenceresilient school. In six inner-city secondary schools, data on violent incidents in school and violent crime in the neighbourhood were gathered, and compared with school practices to minimise violence, accessed through interviews. Some degree of association between the patterns of behaviour and school practices was found: schools with a wider range of wellconnected practices seemed to have less difficult behaviour. Interviews also showed that the different schools had different organisational discourses for construing school violence, its possible causes and the possible solutions. Differences in practices are best understood in connection with differences in these discourses. Some of the features of school discourses are outlined, including their range, their core metaphor and their silences. We suggest that organisational discourse is an important concept in explaining school effects and school differences, and that improvement attempts could have clearer regard to this concept

The Ku-binding motif is a conserved module for recruitment and stimulation of non-homologous end-joining proteins

The Ku-binding motif (KBM) is a short peptide module first identified in APLF that we now show is also present in Werner syndrome protein (WRN) and in Modulator of retrovirus infection homologue (MRI). We also identify a related but functionally distinct motif in XLF, WRN, MRI and PAXX, which we denote the XLF-like motif. We show that WRN possesses two KBMs; one at the N terminus next to the exonuclease domain and one at the C terminus next to an XLF-like motif. We reveal that the WRN C-terminal KBM and XLF-like motif function cooperatively to bind Ku complexes and that the N-terminal KBM mediates Ku-dependent stimulation of WRN exonuclease activity. We also show that WRN accelerates DSB repair by a mechanism requiring both KBMs, demonstrating the importance of WRN interaction with Ku. These data define a conserved family of KBMs that function as molecular tethers to recruit and/or stimulate enzymes during NHEJ

Identifying unmet clinical need in hypertrophic cardiomyopathy using national electronic health records

Introduction: To evaluate unmet clinical need in unselected hypertrophic cardiomyopathy (HCM) patients to determine the risk of a wide range of subsequent cardiovascular disease endpoints and safety endpoints relevant for trial design. Methods: Population based cohort (CALIBER, linked primary care, hospital and mortality records in England, period 1997–2010), all people diagnosed with HCM were identified and matched by age, sex and general practice with ten randomly selected people without HCM. Random-effects Poisson models were used to assess the associations between HCM and cardiovascular diseases and bleeding. Results: Among 3,290,455 eligible people a diagnosis of hypertrophic cardiomyopathy was found in 4 per 10,000. Forty-one percent of the 1,160 individuals with hypertrophic cardiomyopathy were women and the median age was 57 years. The median follow-up was 4.0 years. Compared to general population controls, people with HCM had higher risk of ventricular arrhythmia (incidence rate ratio = 23.53, [95% confidence interval 12.67–43.72]), cardiac arrest or sudden cardiac death (6.33 [3.69–10.85]), heart failure (4.31, [3.30–5.62]), and atrial fibrillation (3.80 [3.04–4.75]). HCM was also associated with a higher incidence of myocardial infarction ([MI] 1.90 [1.27–2.84]) and coronary revascularisation (2.32 [1.46–3.69]).The absolute Kaplan-Meier risks at 3 years were 8.8% for the composite endpoint of cardiovascular death or heart failure, 8.4% for the composite of cardiovascular death, stroke or myocardial infarction, and 1.5% for major bleeding. Conclusions: Our study identified major unmet need in HCM and highlighted the importance of implementing improved cardiovascular prevention strategies to increase life-expectancy of the contemporary HCM population. They also show that national electronic health records provide an effective method for identifying outcomes and clinically relevant estimates of composite efficacy and safety endpoints essential for trial design in rare diseases

Deletions of the region 17p11-13 in advanced melanoma revealed by cytogenetic analysis and fluorescence in situ hybridization

The significance of the p53 tumour-suppressor gene in the oncogenesis of a variety of malignant tumours has been demonstrated over recent years. However, the role of p53 in human malignant melanoma is still unclear. Therefore, we investigated melanoma metastases from 11 patients cytogenetically and with fluorescence in situ hybridization (FISH) after short-term culture, employing a p53 region-specific probe for 17p13.1 and a probe detecting the centromere of chromosome 17. Furthermore, paraffin-embedded tissue samples from nine of these patients were investigated immunohistochemically for expression of the p53 protein. Deletions of the short arm of chromosome 17 were seen in six melanomas in cytogenetic analysis. With FISH, three malignant melanomas had clones with only one p53-allele and an additional four malignant melanomas showed a reduced number of signals at the p53 tumour-suppressor gene locus compared with signals for the centromeric region of chromosome 17. This was confirmed by immunohistochemistry. Our results suggest that the 17p11–13 region is frequently deleted in malignant melanomas and that p53 or other genes located on this band might contribute to the malignant potential of advanced melanoma. © 1999 Cancer Research Campaig

Analysis of Marker-Defined HNSCC Subpopulations Reveals a Dynamic Regulation of Tumor Initiating Properties

Head and neck squamous carcinoma (HNSCC) tumors carry dismal long-term prognosis and the role of tumor initiating cells (TICs) in this cancer is unclear. We investigated in HNSCC xenografts whether specific tumor subpopulations contributed to tumor growth. We used a CFSE-based label retentions assay, CD49f (α6-integrin) surface levels and aldehyde dehydrogenase (ALDH) activity to profile HNSCC subpopulations. The tumorigenic potential of marker-positive and -negative subpopulations was tested in nude (Balb/c nu/nu) and NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) mice and chicken embryo chorioallantoic membrane (CAM) assays. Here we identified in HEp3, SQ20b and FaDu HNSCC xenografts a subpopulation of G0/G1-arrested slow-cycling CD49fhigh/ALDH1A1high/H3K4/K27me3low subpopulation (CD49f+) of tumor cells. A strikingly similar CD49fhigh/H3K27me3low subpopulation is also present in primary human HNSCC tumors and metastases. While only sorted CD49fhigh/ALDHhigh, label retaining cells (LRC) proliferated immediately in vivo, with time the CD49flow/ALDHlow, non-LRC (NLRC) tumor cell subpopulations were also able to regain tumorigenic capacity; this was linked to restoration of CD49fhigh/ALDHhigh, label retaining cells. In addition, CD49f is required for HEp3 cell tumorigenicity and to maintain low levels of H3K4/K27me3. CD49f+ cells also displayed reduced expression of the histone-lysine N-methyltransferase EZH2 and ERK1/2phosphorylation. This suggests that although transiently quiescent, their unique chromatin structure is poised for rapid transcriptional activation. CD49f− cells can “reprogram” and also achieve this state eventually. We propose that in HNSCC tumors, epigenetic mechanisms likely driven by CD49f signaling dynamically regulate HNSCC xenograft phenotypic heterogeneity. This allows multiple tumor cell subpopulations to drive tumor growth suggesting that their dynamic nature renders them a “moving target” and their eradication might require more persistent strategies

T2-weighted cardiovascular magnetic resonance in acute cardiac disease

Cardiovascular magnetic resonance (CMR) using T2-weighted sequences can visualize myocardial edema. When compared to previous protocols, newer pulse sequences with substantially improved image quality have increased its clinical utility. The assessment of myocardial edema provides useful incremental diagnostic and prognostic information in a variety of clinical settings associated with acute myocardial injury. In patients with acute chest pain, T2-weighted CMR is able to identify acute or recent myocardial ischemic injury and has been employed to distinguish acute coronary syndrome (ACS) from non-ACS as well as acute from chronic myocardial infarction