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T-box 2 (TBX2) is a transcription factor involved in mammary development and is known to be overexpressed in a subset of aggressive breast cancers. TBX2 has previously been shown to repress growth control genes such as p14ARF and p21WAF1/cip1. In this study we show that TBX2 drives proliferation in breast cancer cells and this is abrogated after TBX2 small interfering RNA (siRNA) knockdown or after the expression of a dominant-negative TBX2 protein. Using microarray analysis we identified a large cohort of novel TBX2-repressed target genes including the breast tumour suppressor NDRG1 (N-myc downregulated gene 1). We show that TBX2 targets NDRG1 through a previously undescribed mechanism involving the recruitment of early growth response 1 (EGR1). We show EGR1 is required for the ability of TBX2 to repress NDRG1 and drive cell proliferation. We show that TBX2 interacts with EGR1 and that TBX2 requires EGR1 to target the NDRG1 proximal promoter. Abrogation of either TBX2 or EGR1 expression is accompanied by the upregulation of cell senescence and apoptotic markers. NDRG1 can recapitulate these effects when transfected into TBX2-expressing cells. Together, these data identify a novel mechanism for TBX2-driven oncogenesis and highlight the importance of NDRG1 as a growth control gene in breast tissue. [ABSTRACT FROM AUTHOR]

We found that procaspase 8 was overexpressed in non-small-cell lung cancers (NSCLCs) compared with matched normal tissues. The caspase 8 inhibitor FLICE-inhibitory protein (FLIP) was also overexpressed in the majority of NSCLCs. Silencing FLIP induced caspase 8 activation and apoptosis in NSCLC cell lines, but not in normal lung cell lines. Apoptosis induced by FLIP silencing was mediated by the TRAIL death receptors DR4 and DR5, but was not dependent on ligation of the receptors by TRAIL. Furthermore, the apoptosis induced by FLIP silencing was dependent on the overexpression of procaspase 8 in NSCLC cells. Moreover, in NSCLC cells, but not in normal cells, FLIP silencing induced co-localization of DR5 and ceramide, and disruption of this co-localization abrogated apoptosis. FLIP silencing supra-additively increased TRAIL-induced apoptosis of NSCLC cells; however, normal lung cells were resistant to TRAIL, even when FLIP was silenced. Importantly, FLIP silencing sensitized NSCLC cells but not normal cells to chemotherapy in vitro, and silencing FLIP in vivo retarded NSCLC xenograft growth and enhanced the anti-tumour effects of cisplatin. Collectively, our results suggest that due to frequent procaspase 8 overexpression, NSCLCs may be particularly sensitive to FLIP-targeted therapies. [ABSTRACT FROM AUTHOR]

This article describes the technique of saphenous vein peripherally inserted central catheter placement, which is used as an alternative site for venous access in our institution, and examines saphenous vein peripherally inserted central catheter safety issues and indications. Three end-stage renal failure patients, two patients diagnosed with malignancy and one renal transplant patient had a saphenous peripherally inserted central catheter (inserted between March 2004 and March 2006 for antibiotics or chemotherapy. The average duration of placement was 16.2 days (range 3–42 days). All insertions were carried out successfully, with an average screening time of 81.2 s. None of the patients experienced any major complications. Two patients developed localized cellulitis at the insertion site. [ABSTRACT FROM AUTHOR]

This article discusses the importance of collaboration with patient advocates for the improvement of treatment of patients diagnosed with various diseases. Twenty years ago American HIV infected persons or AIDS patients angered by social discrimination and ignorance surrounding the disease began to advocate for change. They wanted access to better treatments, early access to promising drugs, more equitable access to care and an end of the widespread stigma and prejudice confronted by people with HIV or AIDS. They used variuos tactics including acts of civil disobedience to raise public awareness of their plight and to compel policy-makers, drug regulators, researchers, clinicians and pharmaceutical companies alike to listen to their opinion and include them in the decision-making process. Patient organizations represent interests of a defined group of patientsand can be identified because they have patients as members and by the presence of patient representatives on their boards. Advocacy organizations for patients with cancer have been established in many European countries but the maturity and effectiveness of these groups varies among countries and among cancer types.

Le pectus excavatum est la malformation thoracique congénitale la plus fréquente puisqu'elle affecte une personne sur 500. De nombreuses techniques chirurgicales ont été proposées : certaines peuvent être suivies de complications ou de résultats insuffisants alors même que leur utilité fonctionnelle est très controversée. Une chirurgie secondaire utilisant un implant 3D profond sur mesure, peut être une solution élégante, efficace et sûre comparée aux autres. Elle permet d'obtenir le bon résultat esthétique espéré par les patients exempts de tout contexte respiratoire ou cardio-vasculaire. Most common congenital malformation of the thorax, Pectus Excavatum affects about one in 500 people. Several surgical or medical techniques have been proposed. Some are followed by complications or insufficient results even though their constant functional value is highly controversial. Secondary surgery with a deep customized 3D elastomer implant, may be an elegant effective and safe solution compared to others; it allows a good aesthetic result expected by patients in the absence of any respiratory or cardio-vascular functional context. [ABSTRACT FROM AUTHOR]

Autonomic nervous system dysfunction has been implicated in the pathophysiology of irritable bowel syndrome (IBS). This study characterized the autonomic response to rectal distension in IBS using baroreceptor sensitivity (BRS), a measure of autonomic function. Rectal bag pressure, discomfort, pain, ECG, blood pressure and BRS were continuously measured before, during and after rectal distension in 98 healthy volunteers (34 ± 12 years old, 52 females) and 39 IBS patients (39 ± 11 years old, 35 females). In comparison with the healthy volunteers, IBS patients experienced significantly more discomfort (69 ± 2.2% vs 56 ± 3.6%; P < 0.05), but not pain (9 ± 1.4% vs 6 ± 2.4%; ns) with rectal distension despite similar distension pressures (51 ± 1.4 vs 54 ± 2.4 mmHg; ns) and volumes (394 ± 10.9 vs 398 ± 21.5 mL; ns). With rectal distension, heart rate increased in both healthy volunteers (66 ± 1 to 71 ± 1 bpm; P < 0.05) and IBS patients (66 ± 2 to 74 ± 3 bpm; P < 0.05). Systolic blood pressure also increased in both healthy volunteers (121 ± 2 to 143 ± 2 mmHg; P < 0.05) and patients (126 ± 3 to 153 ± 4 mmHg (P < 0.05) as did diastolic blood pressure, 66 ± 2 to 80 ± 2 mmHg (P < 0.05), compared with 68 ± 3 to 84 ± 3 mmHg (P < 0.05) in IBS patients. The systolic blood pressure increase observed in IBS patients was greater than that seen in healthy volunteers and remained elevated in the post distension period (139 ± 3 mmHg vs 129 ± 2 mmHg; P < 0.05). IBS patients had lower BRS (7.85 ± 0.4 ms mmHg−1) compared with healthy volunteers (9.4 ± 0.3; P < 0.05) at rest and throughout rectal distension. Greater systolic blood pressure response to rectal distension and associated diminished BRS suggests a compromise of the autonomic nervous system in IBS patients. [ABSTRACT FROM AUTHOR]

We evaluated autonomic function, symptoms and psychological parameters in patients with ulcerative colitis (UC), Crohn’s disease (CD) and matched controls to assess whether UC patients have greater basal sympathetic autonomic activity. Outpatients with UC ( n = 15), CD ( n = 13) and healthy controls ( n = 28) underwent spectral analysis of heart rate variability to assess cardiac autonomic function, a methacholine challenge to assess cholinergic pulmonary responsiveness, and questionnaires assessing disease severity, anxiety and depression. UC but not CD patients had greater sympathetic activity than controls with increased absolute (6600 vs 5884; P = 0.04) and relative (62.8% vs 54.8%; P = 0.02) low frequency areas. This was not because of increased overall autonomic nervous system (ANS) activation and was independent of disease activity. In UC patients, trait (personality-related) anxiety correlated strongly with disease symptoms ( R = 0.84; P < 0.001) and quality of life ( R = −0.81; P < 0.001) while situational (state) anxiety did not. In CD patients, ANS measures were similar to controls and disease activity was unrelated to psychological measures. Cholinergic pulmonary responsiveness was normal in both UC and CD patients. UC patients have an increased sympathetic ANS activity which is independent of symptom severity. In these patients symptom severity is strongly associated with measures of personality related (but not current) anxiety. [ABSTRACT FROM AUTHOR]

A historical review of research on sea fog is presented. The period of interest is essentially the twentieth century, beginning with the celebrated work of G. I. Taylor in the aftermath of the Titanic tragedy. It has been argued that relative maxima in fog frequency over the North Atlantic (including the Brit-ish Isles and the Grand Banks of Newfoundland) and the North Pacific (including the U.S. West Coast) has led to major contributions by scientists in England and the United States. The early work (pre–World War II) tended to be phenomenological—that is, conceptual with broad inference from statistical summaries. Yet, this early work laid the foundation for the numerical modeling that came with the advent of computers in the postwar period. The subtleties associated with sea fog formation and maintenance are explored by analyzing some of the results from the numerical simulations. The essay ends with a speculative view on our prospects for a more complete understanding of sea fog in light of the earlier contributions. [ABSTRACT FROM AUTHOR]

Recent and historical events illustrate the vulnerabilities of the U.S. west to extremes in precipitation that result from a range of meteorological phenomena. This vision provides an approach to mitigating impacts of such weather and water extremes that is tailored to the unique meteorological conditions and user needs of the Western U.S. in the 21st Century. It includes observations for tracking, predicting, and managing the occurrence and impacts of major storms and is informed by a range of user-requirements, workshops, scientific advances, and technological demonstrations. The vision recommends innovations and enhancements to existing monitoring networks for rain, snow, snowmelt, flood, and their hydrometeorological precursor conditions, including radars to monitor winds aloft and precipitation, soil moisture sensors, stream gages, and SNOTEL enhancements, as well as entirely new observational tools. Key limitations include monitoring the fuel for heavy precipitation, storms over the eastern Pacific, precipitation distributions, and snow and soil moisture conditions. This article presents motivation and context, and describes key components, an implementation strategy, and expected benefits. This document supports a Resolution of the Western States Water Council for addressing extreme events. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the effect of pre-treatment verification imaging with megavoltage X-rays on cancer and normal cell survival in vitro and to compare the findings with theoretically modelled data. Since the dose received from pre-treatment imaging can be significant, the incorporation of this dose at the planning stage of treatment has been suggested. Methods: The impact of imaging dose incorporation on cell survival was investigated by clonogenic assay of irradiated DU-145 prostate cancer, H460 non-small-cell lung cancer and AGO-1522b normal tissue fibroblast cells. Clinically relevant imaging-to-treatment times of 7.5 and 15 min were chosen for this study. The theoretical magnitude of the loss of radiobiological efficacy due to sublethal damage repair was investigated using the Lea-Catcheside dose protraction factor model. Results: For the cell lines investigated, the experimental data showed that imaging dose incorporation had no significant impact on cell survival. These findings were in close agreement with theoretical results. Conclusion: For the conditions investigated, the results suggest that allowance for the imaging dose at the planning stage of treatment should not adversely affect treatment efficacy. Advances in knowledge: There is a paucity of data in the literature on imaging effects in radiotherapy. This article presents a systematic study of imaging dose effects on cancer and normal cell survival, providing both theoretical and experimental evidence for clinically relevant imaging doses and imaging-to-treatment times. The data provide a firm foundation for further study into this highly relevant area of research. [ABSTRACT FROM AUTHOR]

Ancient blue oak trees are still widespread across the foothills of the Coast Ranges, Cascades, and Sierra Nevada in California. The most extensive tracts of intact old-growth blue oak woodland appear to survive on rugged and remote terrain in the southern Coast Ranges and on the foothills west and southwest of Mt. Lassen. In the authors' sampling of old-growth stands,most blue oak appear to have recruited to the canopy in the middle to late nineteenth century. The oldest living blue oak tree sampled was over 459 years old, and several dead blue oak logs had over 500 annual rings. Precipitation sensitive tree-ring chronologies up to 700 years long have been developed from old blue oak trees and logs. Annual ring-width chronologies of blue oak are strongly correlated with cool season precipitation totals, streamflow in the major rivers of California, and the estuarine water quality of San Francisco Bay. A new network of 36 blue oak chronologies records spatial anomalies in growth that arise from latitudinal changes in the mean storm track and location of land-falling atmospheric rivers. These long, climate-sensitive blue oak chronologies have been used to reconstruct hydroclimatic history in California and will help to better understand and manage water resources. The environmental history embedded in blue oak growth chronologies may help justify efforts to conserve these authentic old-growth native woodlands. [ABSTRACT FROM AUTHOR]

Flattening filter free (FFF) linear accelerators allow for an increase in instantaneous dose-rate of the x-ray pulses by a factor of 2-6 over the conventional flattened output. As a result, radiobiological investigations are being carried out to determine the effect of these higher dose-rates on cell response. The studies reported thus far have presented conflicting results, highlighting the need for further investigation. To determine the radiobiological impact of the increased dose-rates from FFF exposures a Varian Truebeam medical linear accelerator was used to irradiate two human cancer cell lines in vitro, DU-145 prostate and H460 non-small cell lung, with both flattened and FFF 6 MV beams. The fluence profile of the FFF beam was modified using a custom-designed Nylon compensator to produce a similar dose profile to the flattened beam (6X) at the cell surface but at a higher instantaneous dose-rate. For both cell lines there appeared to be no significant change in cell survival. Curve fitting coefficients for DU145 cells irradiated with constant average dose-rates were 6X: α = 0.09 ± 0.03, β = 0.03 ± 0.01 and 6FFF: α = 0.14 ± 0.13, β = 0.03 ± 0.02 with a significance of p = 0.75. For H460 cells irradiated with the same instantaneous dose-rate but different average dose-rate the fit coefficients were 6FFF (low dose-rate): α = 0.21 ± 0.11, 0.07 ± 0.02 and 6FFF (high dose-rate): α = 0.21 ± 0.16, 0.07 ± 0.03, with p = 0.79. The results indicate that collective damage behaviour does not occur at the instantaneous dose-rates investigated here and that the use of either modality should result in the same clinical outcome, however this will require further validation in vivo. [ABSTRACT FROM AUTHOR]

Mucous cell size and distribution were investigated in the skin of five salmon using a novel stereology-based methodology: one (48 cm) fish to test 15 tissue treatment combinations on measures of cell area and density on the dorsolateral region and, using the most suitable treatment, we mapped mucous cell differences between body regions on four (52 cm) salmon, comprising a male and a female on each of two diets. The section site, decalcification, embedding medium and plane of sectioning all impacted significantly on mucous cell size, whereas mucous cell density is more robust. There were highly significant differences in both mucosal density and mean mucous cell size depending on body site: the dorsolateral skin of the four salmon had significantly denser (about 8% of skin area) and larger (mean about 160 μm2) mucous cells, whereas the lowest mean density (about 4%) and smallest mean area (115 μm2) were found on the head. We found that 100 random measurements may be sufficient to distinguish differences >7 μm2 in mean mucous cell areas. The results further suggest that salmon exhibit a dynamic repeatable pattern of mucous cell development influenced by sex, diet and possibly strain and season. [ABSTRACT FROM AUTHOR]

A correction to the article "Vagal Dysfunction in Irritable Bowel Syndrome Assessed by Rectal Distension and Baroreceptor Sensitivity" that was published in a 2008 issue is presented.

FLIP is a potential anti-cancer therapeutic target that inhibits apoptosis by blocking caspase 8 activation by death receptors. We report a novel interaction between FLIP and the DNA repair protein Ku70 that regulates FLIP protein stability by inhibiting its polyubiquitination. Furthermore, we found that the histone deacetylase (HDAC) inhibitor Vorinostat (SAHA) enhances the acetylation of Ku70, thereby disrupting the FLIP/Ku70 complex and triggering FLIP polyubiquitination and degradation by the proteasome. Using in vitro and in vivo colorectal cancer models, we further demonstrated that SAHA-induced apoptosis is dependant on FLIP downregulation and caspase 8 activation. In addition, an HDAC6-specific inhibitor Tubacin recapitulated the effects of SAHA, suggesting that HDAC6 is a key regulator of Ku70 acetylation and FLIP protein stability. Thus, HDAC inhibitors with anti-HDAC6 activity act as efficient post-transcriptional suppressors of FLIP expression and may, therefore, effectively act as 'FLIP inhibitors'. [ABSTRACT FROM AUTHOR]

The article offers information on the method of quantifying salmonid mucous cells. It states that the primary defence mechanism of fish exposed to an infectious or damaging agent is the physical barrier of skin, gills and gastrointestinal tract and their protection mechanisms associated with the innate immune defense system, the mucosal epithelium.

Investigates the incidence of circulating tumor cells in patients with breast carcinoma. Assessment of patients who underwent bone marrow respiration aspiration from bilateral iliac crests and right rib; Isolation of the mononuclear cell layer using Ficoll-Paque density centrifugation technique; Sizes of tumor.

Abstract: According to EUSOMA position paper ‘The requirements of a specialist breast unit’, each breast unit should have a core team made up of health professionals who have undergone specialist training in breast cancer. In this paper, on behalf of EUSOMA, authors have identified the standards of training in breast cancer, to harmonise and foster breast care training in Europe. The aim of this paper is to contribute to the increase in the level of care in a breast unit, as the input of qualified health professionals increases the quality of breast cancer patient care. [Copyright &y& Elsevier]

Evaluates long-term trends in average maximum and minimum temperatures, threshold temperatures, and growing season in eastern Colorado, USA, to explore the potential shortcomings of many climate-change studies that either: (1) generalize regional patterns from single stations, single seasons, or a few parameters over short duration from averaging dissimilar stations; or (2) generalize an average regional pattern from coarse-scale general circulation models. Details of study using information garnered by several weather stations; Evidence of a sub-regional cooling in autumn's maximum temperatures; Data indicating there were many geographic anomalies where neighboring weather stations differed greatly in the magnitude of change or where they had significant and opposite trends; Results suggesting that sub-regional spatial and seasonal variation cannot be ignored when evaluating the direction and magnitude of climate change.

Purpose A double lung donor may be split, with a single lung transplanted sequentially into two different recipients by one team. This minimizes utilization of hospital staff resources, day time theater access and supports donor to transplant conversion rates. This is a retrospective institutional review of the first 12 cases assessing the impact of extended ischemic time (for the delayed second lung transplant recipient) on length of stay (LOS), intermediate term graft function and survival. Methods Twelve sequential single lung transplants were performed from 6 donors between August 2016 and September 2017. Basic data for donors and recipients including outcomes (ischemic time, ICU stay, total hospital stay, 30 day mortality, 12-month survival including pulmonary function tests (PFTs)) were recorded. Borderline lungs were implanted to the EVLP circuit and reperfused using acellular supplemented Steen Solution (Vitrolife, Göteborg, Sweden). Recipients were categorized into 2 groups: G1 for patients who received the 1st lung, hence having a shorter ischemic time (whether they had EVLP or not), G2 for patients who received the 2nd lung, hence a longer ischemic time. 3 patients received EVLP reconditioned lungs. Results Donor data (n = 6) were: age, 44.2 ± 8.33 years; female/male, 5:1; cause of death: intracranial haemorrhage 4(66.6%), hypoxic brain injury 1(16.6%) and traumatic brain injury 1(16.6%). Mean LAS Score was similar for both groups (44.9 G1 and 41.7 G2, p value=0.64). Mean ischemic time from donor cross clamp to reperfusion was 389 minutes for G1 and 708 minutes for G2. There was no significant difference in ICU stay: 14.7 days vs 6.0 days with a quicker discharge from ITU in the G2(p value=0.20). The mean Hospital LOS was 32.3 vs 20.3 days, (p value= 0.35) Mean FEV 1 at 3 months in G1 was 2.4 L (79.7%) and in G2 was 2.0 L (68.4%) (p value=0.38). No all cause 30 day mortality in both groups. At 1-year 2 patients had died from an unexpected bradycardic cardiac arrest. Conclusion SLT if limited resources are available maximize on donor to transplant conversion rates. Donor ischemic lung time is not a deterrent in the era of EVLP. SLT into two recipients by a single theater service is feasible, cost-effective and safe. [ABSTRACT FROM AUTHOR]

The article presents a case study of 33-year-old Caucasian male smoker who was presented to rapid access lung cancer clinic with a single episode of moderate haemoptysis and didnt' posses any other respiratory or systemic symptoms.

Abstract: Lack of suitable donor lungs is still a major limitation of lung transplantation. Extended donor acceptance criteria combined with innovative assessment tools can be used to expand the number of suitable organs. We describe a successful transplantation of lungs retrieved from a donor who had undergone aortic root replacement 9 days before donation after cardiac death. The lungs were assessed using ex-vivo lung perfusion. [Copyright &y& Elsevier]