Cutaneous metastases of breast carcinoma: a case report

© 2009 Vano-Galvan et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Explaining the effects of an intervention designed to promote evidence-based diabetes care : a theory-based process evaluation of a pragmatic cluster randomised controlled trial

Background The results of randomised controlled trials can be usefully illuminated by studies of the processes by which they achieve their effects. The Theory of Planned Behaviour (TPB) offers a framework for conducting such studies. This study used TPB to explore the observed effects in a pragmatic cluster randomised controlled trial of a structured recall and prompting intervention to increase evidence-based diabetes care that was conducted in three Primary Care Trusts in England. Methods All general practitioners and nurses in practices involved in the trial were sent a postal questionnaire at the end of the intervention period, based on the TPB (predictor variables: attitude; subjective norm; perceived behavioural control, or PBC). It focussed on three clinical behaviours recommended in diabetes care: measuring blood pressure; inspecting feet; and prescribing statins. Multivariate analyses of variance and multiple regression analyses were used to explore changes in cognitions and thereby better understand trial effects. Results Fifty-nine general medical practitioners and 53 practice nurses (intervention: n = 55, 41.98% of trial participants; control: n = 57, 38.26% of trial participants) completed the questionnaire. There were no differences between groups in mean scores for attitudes, subjective norms, PBC or intentions. Control group clinicians had 'normatively-driven' intentions (i.e., related to subjective norm scores), whereas intervention group clinicians had 'attitudinally-driven' intentions (i.e., related to attitude scores) for foot inspection and statin prescription. After controlling for effects of the three predictor variables, this group difference was significant for foot inspection behaviour (trial group × attitude interaction, beta = 0.72, p < 0.05; trial group × subjective norm interaction, beta = -0.65, p < 0.05). Conclusion Attitudinally-driven intentions are proposed to be more consistently translated into action than normatively-driven intentions. This proposition was supported by the findings, thus offering an interpretation of the trial effects. This analytic approach demonstrates the potential of the TPB to explain trial effects in terms of different relationships between variables rather than differences in mean scores. This study illustrates the use of theory-based process evaluation to uncover processes underlying change in implementation trials.European Union ReBEQI projec

Video-assisted mediastinoscopic transhiatal esophagectomy combined with laparoscopy for esophageal cancer

<p>Abstract</p> <p>Background</p> <p>Minimally invasive transhiatal esophagectomy for esophageal cancer includes mediastinoscopic and laparoscopic transhiatal esophagectomy. It is inadequate in both two techniques. It is impossible to dissect the lower esophagus with single mediastinoscopy or the upper and middle esophagus with single laparoscopy. We use mediastinoscopy combined with laparoscopy to dissect the whole esophagus and stomach including lymph node dissection. In addition, laparoscopic gastric mobilization leads to less trauma than an open gastroplasty.</p> <p>Methods</p> <p>40 cases of video-assisted mediastinoscopic transhiatal esophagectomy were performed and divided into two groups.32 patients were received surgical therapy of single mediastinoscopic esophagectomy with open gastroplasty in group A, while 8 patients were received surgical therapy of mediastinoscopic esophagectomy combined with laparoscopic lower esophageal and gastric dissection in group B. The perioperative complications were recorded.</p> <p>Results</p> <p>Video-assisted mediastinoscopic transhiatal esophagectomy was performed successfully both in group A and B. It suggested that mediastinoscopy combined with laparoscopy be better than single mediastinoscopy because of less blood loss, less pain, shorter ICU stay and complete lower mediastinal lymph nodes resection.</p> <p>Conclusions</p> <p>Video-assisted mediastinoscopic transhiatal esophagectomy combined with laparoscopy is a safe and minimally invasive technique with whole esophagus and mediastinal lymph node dissection in the clear visualization of the mediastinum, reducing the abdominal trauma.</p

MicroRNAs in cardiac arrhythmia: DNA sequence variation of MiR-1 and MiR-133A in long QT syndrome.

Long QT syndrome (LQTS) is a genetic cardiac condition associated with prolonged ventricular repolarization, primarily a result of perturbations in cardiac ion channels, which predisposes individuals to life-threatening arrhythmias. Using DNA screening and sequencing methods, over 700 different LQTS-causing mutations have been identified in 13 genes worldwide. Despite this, the genetic cause of 30-50% of LQTS is presently unknown. MicroRNAs (miRNAs) are small (∼ 22 nucleotides) noncoding RNAs which post-transcriptionally regulate gene expression by binding complementary sequences within messenger RNAs (mRNAs). The human genome encodes over 1800 miRNAs, which target about 60% of human genes. Consequently, miRNAs are likely to regulate many complex processes in the body, indeed aberrant expression of various miRNA species has been implicated in numerous disease states, including cardiovascular diseases. MiR-1 and MiR-133A are the most abundant miRNAs in the heart and have both been reported to regulate cardiac ion channels. We hypothesized that, as a consequence of their role in regulating cardiac ion channels, genetic variation in the genes which encode MiR-1 and MiR-133A might explain some cases of LQTS. Four miRNA genes (miR-1-1, miR-1-2, miR-133a-1 and miR-133a-2), which encode MiR-1 and MiR-133A, were sequenced in 125 LQTS probands. No genetic variants were identified in miR-1-1 or miR-133a-1; but in miR-1-2 we identified a single substitution (n.100A> G) and in miR-133a-2 we identified two substitutions (n.-19G> A and n.98C> T). None of the variants affect the mature miRNA products. Our findings indicate that sequence variants of miR-1-1, miR-1-2, miR-133a-1 and miR-133a-2 are not a cause of LQTS in this cohort

Meta-analysis of Genome Wide Association Studies Identifies Genetic Markers of Late Toxicity Following Radiotherapy for Prostate Cancer.

Nearly 50% of cancer patients undergo radiotherapy. Late radiotherapy toxicity affects quality-of-life in long-term cancer survivors and risk of side-effects in a minority limits doses prescribed to the majority of patients. Development of a test predicting risk of toxicity could benefit many cancer patients. We aimed to meta-analyze individual level data from four genome-wide association studies from prostate cancer radiotherapy cohorts including 1564 men to identify genetic markers of toxicity. Prospectively assessed two-year toxicity endpoints (urinary frequency, decreased urine stream, rectal bleeding, overall toxicity) and single nucleotide polymorphism (SNP) associations were tested using multivariable regression, adjusting for clinical and patient-related risk factors. A fixed-effects meta-analysis identified two SNPs: rs17599026 on 5q31.2 with urinary frequency (odds ratio [OR] 3.12, 95% confidence interval [CI] 2.08-4.69, p-value 4.16×10(-8)) and rs7720298 on 5p15.2 with decreased urine stream (OR 2.71, 95% CI 1.90-3.86, p-value=3.21×10(-8)). These SNPs lie within genes that are expressed in tissues adversely affected by pelvic radiotherapy including bladder, kidney, rectum and small intestine. The results show that heterogeneous radiotherapy cohorts can be combined to identify new moderate-penetrance genetic variants associated with radiotherapy toxicity. The work provides a basis for larger collaborative efforts to identify enough variants for a future test involving polygenic risk profiling.This work was supported by Cancer Research UK (C1094/A11728 to CMLW and NGB for the RAPPER study, C26900/A8740 to GCB, and C8197/A10865 to AMD), the Royal College of Radiologists (C26900/ A8740 to GCB), the National Institute for Health Research (GCB; no grant number), Addenbrooke's Charitable Trust (GCB; no grant number), Institute of Cancer Research (National Institute for Health Research) Biomedical Research Centre (C46/A2131 to DPD and SG), the National Institute for Health Research Cambridge Biomedical Research Centre (NGB; no grant number), UK Medical Research Council (RG70550 to LD), the Joseph Mitchell Trust (AMD; no grant number), the Experimental Cancer Medicine Centre (CMLW; no grant number), Cancer Research UK Program grant Section of Radiotherapy (C33589/ A19727 to SLG), the United States National Institutes of Health (1R01CA134444 to BSR and HO, 2P30CA014520-34 to SB, and 1K07CA187546-01A1 to SLK), the American Cancer Society (RSGT-05- 200-01-CCE to BSR), the U.S. Department of Defense (PC074201 to BSR and HO), Mount Sinai Tisch Cancer Institute Developmental Fund Award (BSR; no grant number), the Instituto de Salud Carlos III (FIS PI10/00164 and PI13/02030 to AV and PI13/01136 to AC), Fondo Europeo de Desarrollo Regional (FEDER 2007–2013 to AV and AC; no grant number), Instituto de Salud Carlos III (FIS PI10/00164 and PI13/ 02030 to AV and PI13/01136 to AC), Xunta de Galicia and the European Social Fund (POS-A/2013/034 to LF), and the Alberta Cancer Board Research Initiative Program (103.0393.71760001404 to MP). AMD receives support from the REQUITE study, which is funded by the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 601826. Laboratory infrastructure for the RAPPER study was funded by Cancer Research UK [C8197/A10123] and the Manchester Experimental Cancer Medicine Centre. The RAPPER cohort comprises individuals and data recruited into the RT01 and CHHiP UK radiotherapy trials. The RT01 trial was supported by the UK Medical Research Council. The CHHiP trial (CRUK/06/016) was supported by the Department of Health and Cancer Research UK (C8262/A7253); trial recruitment was facilitated within centers by the National Institute for Health Research Cancer Research Network. DPD and SLG acknowledge NHS funding to the NIHR Biomedical Research Centre at the Royal Marsden NHS Foundation Trust and Institute of Cancer Research.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.ebiom.2016.07.02

Study of Bc+B_c^+ decays to the K+K−π+K^+K^-\pi^+ final state and evidence for the decay Bc+→χc0π+B_c^+\to\chi_{c0}\pi^+

A study of $B_c^+\to K^+K^-\pi^+$ decays is performed for the first time using data corresponding to an integrated luminosity of 3.0 $\mathrm{fb}^{-1}$ collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of $7$ and $8$ TeV. Evidence for the decay $B_c^+\to\chi_{c0}(\to K^+K^-)\pi^+$ is reported with a significance of 4.0 standard deviations, resulting in the measurement of $\frac{\sigma(B_c^+)}{\sigma(B^+)}\times\mathcal{B}(B_c^+\to\chi_{c0}\pi^+)$ to be $(9.8^{+3.4}_{-3.0}(\mathrm{stat})\pm 0.8(\mathrm{syst}))\times 10^{-6}$. Here $\mathcal{B}$ denotes a branching fraction while $\sigma(B_c^+)$ and $\sigma(B^+)$ are the production cross-sections for $B_c^+$ and $B^+$ mesons. An indication of $\bar b c$ weak annihilation is found for the region $m(K^-\pi^+)<1.834\mathrm{\,Ge\kern -0.1em V\!/}c^2$, with a significance of 2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html, link to supplemental material inserted in the reference

A High-Throughput Screen Identifies a New Natural Product with Broad-Spectrum Antibacterial Activity

Due to the inexorable invasion of our hospitals and communities by drug-resistant bacteria, there is a pressing need for novel antibacterial agents. Here we report the development of a sensitive and robust but low-tech and inexpensive high-throughput metabolic screen for novel antibiotics. This screen is based on a colorimetric assay of pH that identifies inhibitors of bacterial sugar fermentation. After validation of the method, we screened over 39,000 crude extracts derived from organisms that grow in the diverse ecosystems of Costa Rica and identified 49 with reproducible antibacterial effects. An extract from an endophytic fungus was further characterized, and this led to the discovery of three novel natural products. One of these, which we named mirandamycin, has broad-spectrum antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Vibrio cholerae, methicillin-resistant Staphylococcus aureus, and Mycobacterium tuberculosis. This demonstrates the power of simple high throughput screens for rapid identification of new antibacterial agents from environmental samples