Overexpression of proto-oncogene FBI-1 activates membrane type 1-matrix metalloproteinase in association with adverse outcome in ovarian cancers

<p>Abstract</p> <p>Background</p> <p>FBI-1 (factor that binds to the inducer of short transcripts of human immunodeficiency virus-1) is a member of the POK (POZ and Kruppel) family of transcription factors and play important roles in cellular differentiation and oncogenesis. Recent evidence suggests that FBI-1 is expressed at high levels in a subset of human lymphomas and some epithelial solid tumors. However, the function of FBI-1 in human ovarian cancers remains elusive.</p> <p>Results</p> <p>In this study, we investigated the role of FBI-1 in human ovarian cancers, in particularly, its function in cancer cell invasion via modulating membrane type 1-matrix metalloproteinase (MT1-MMP). Significantly higher FBI-1 protein and mRNA expression levels were demonstrated in ovarian cancers samples and cell lines compared with borderline tumors and benign cystadenomas. Increased FBI-1 mRNA expression was correlated significantly with gene amplification (P = 0.037). Moreover, higher FBI-1 expression was found in metastatic foci (P = 0.036) and malignant ascites (P = 0.021), and was significantly associated with advanced stage (P = 0.012), shorter overall survival (P = 0.032) and disease-free survival (P = 0.016). <it>In vitro</it>, overexpressed FBI-1 significantly enhanced cell migration and invasion both in OVCA 420 and SKOV-3 ovarian carcinoma cells, irrespective of <it>p53 </it>status, accompanied with elevated expression of MT1-MMP, but not MMP-2 or TIMP-2. Moreover, knockdown of MT1-MMP abolished FBI-1-mediated cell migration and invasion. Conversely, stable knockdown of FBI-1 remarkably reduced the motility of these cells with decreased expression of MT1-MMP. Promoter assay and chromatin immunoprecipitation study indicated that FBI-1 could directly interact with the promoter spanning ~600bp of the 5'-flanking sequence of MT1-MMP and enhanced its expression in a dose-dependent manner. Furthermore, stable knockdown and ectopic expression of FBI-1 decreased and increased cell proliferation respectively in OVCA 420, but not in the p53 null SKOV-3 cells.</p> <p>Conclusions</p> <p>Our results suggested an important role of FBI-1 in ovarian cancer cell proliferation, cell mobility, and invasiveness, and that FBI-1 can be a potential target of chemotherapy.</p

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

人種／エスニシティ、階級、およびジェンダー : アメリカにおける理論と研究の発展

　エスター・アンリン・チャウ教授は、University of California at Los Angeles で博士号を取得し、現在は米国ワシントンD.C. のアメリカン大学社会学部の教授である。1998年から1999年までアメリカ社会学協会のアジアおよびアジア系アメリカ部門の委員長に就任している。\r\n　チャウ教授の関心は人種／民族、階級、ジェンダー、グローバリズムと社会変化、移民問題など幅広く、特にアジア系アメリカ女性の仕事や家庭について精力的に研究活動を行っている。\r\n　著書には、1997年に The Myers Center Award for the Study of Human Rights in North America を受賞した Race, Class and Gender (1996) の他、Women, the Family, and Policy: A Global Perspective (1994) 等がある。\r\n　本稿は、平成11年10月2日に開催されたお茶の水女子大学ジェンダー研究センター主催の公開講演会「ジェンダー、エスニシティ、人種」において発表された講演の原稿である

Branching out: Feasibility of examining the effects of greenspace on mental health after traumatic brain injury

Aim: This pilot study’s aim was to determine the feasibility of examining the effects of an environmental variable (i.e., tree canopy coverage) on mental health after sustaining a brain injury. Methods: A secondary data analysis was conducted leveraging existing information on mental health after moderate to severe traumatic brain injury (TBI) from the TBI Model System. Mental health was measured using PHQ-9 (depression) and GAD-7 (anxiety) scores. The data were compared with data on tree canopy coverage in the state of Texas that was obtained from the Multi-Resolution Land Characteristics (MRLC) Consortium using GIS analysis. Tree canopy coverage as an indicator of neighborhood socioeconomic status was also examined using the Neighborhood SES Index. Results: Tree canopy coverage had weak and non-significant correlations with anxiety and depression scores, as well as neighborhood socioeconomic status. Data analysis was limited by small sample size. However, there is a higher percentage (18.8%) of participants who reported moderate to severe depression symptoms in areas with less than 30% tree canopy coverage, compared with 6.6% of participants who endorsed moderate to severe depression symptoms and live in areas with more than 30% tree canopy coverage (there was no difference in anxiety scores). Conclusion: Our work confirms the feasibility of measuring the effects of tree canopy coverage on mental health after brain injury and warrants further investigation into examining tree canopy coverage and depression after TBI. Future work will include nationwide analyses to potentially detect significant relationships, as well as examine differences in geographic location

Agreement between self-/home-measured and assessor-measured waist circumference at three sites in adolescents/children

<div><p>The objective of this study was to assess the validity of the self-/home-measured waist circumference (WC) method in children/adolescents at three sites: at the level of the umbilicus, immediately above the iliac crest, and at the midpoint of the lower margin of the last palpable rib and top of the iliac crest. A cross-sectional study of 3360 Hong Kong Chinese children/adolescents was conducted, with 2980 (88.7%) participants included in the final analysis. The WC of children aged 6 to 9 was measured at the three sites by their parent/guardian at home followed by measurement by trained assessors at school within one week. Children/adolescents between the ages of 10 and 17 self-measured their WC at the three sites during school hours, followed by measurements by the trained assessors. Bland-Altman limits of agreement (LOA) analysis was performed to evaluate between-measurement agreement. The difference between assessor- and self-/home-measured WC was defined as ≤ ±2.5 cm for the upper and lower LOA at all three sites as an a priori criterion based on the assessor-measured inter-rater results. The results showed that most measurements (about 96%) at each site was within 95% of the LOA. Of the three measurement sites, the smallest LOA interval width was found at the umbilicus site, with an upper LOA of 5.08 and 7.13 and lower LOA of -2.61 and -3.43 in boys and girls, respectively. In conclusion, the range of LOA was relatively large, exceeding the acceptable limits of the predefined a priori criterion of upper and lower LOA, and thus suggesting disagreement between the two measurement methods. The use of WC as a measure of abdominal obesity in clinical practice/epidemiological studies should be restricted to measurement by trained health professionals/research staff.</p></div