Synchronous colorectal cancer: Clinical, pathological and molecular implications

Synchronous colorectal carcinoma refers to more than one primary colorectal carcinoma detected in a single patient at initial presentation. A literature review has shown that the prevalence of the disease is approximately 3.5% of all colorectal carcinomas. This disease has a male to female ratio of 1.8:1. The mean age at presentation of patients with synchronous colorectal cancer is in the early half of the seventh decade. Patients with inflammatory bowel diseases (ulcerative colitis and Crohn’s disease), hereditary non-polyposis colorectal cancer, familial adenomatous polyposis and serrated polyps/hyperplastic polyposis are known to have a higher risk of synchronous colorectal carcinoma. These predisposing factors account for slightly more than 10% of synchronous colorectal carcinomas. Synchronous colorectal carcinoma is more common in the right colon when compared to solitary colorectal cancer. On pathological examination, some synchronous colorectal carcinomas are mucinous adenocarcinomas. They are usually associated with adenomas and metachronous colorectal carcinomas. Most of the patients with synchronous colorectal cancer have two carcinomas but up to six have been reported in one patient. Patients with synchronous colorectal carcinoma have a higher proportion of microsatellite instability cancer than patients with a solitary colorectal carcinoma. Also, limited data have revealed that in many synchronous colorectal carcinomas, carcinomas in the same patient have different patterns of microsatellite instability status, p53 mutation and K-ras mutation. Overall, the prognosis of patients with synchronous colorectal carcinoma is not significantly different from that in patients with solitary colorectal carcinoma, although a marginally better prognosis has been reported in patients with synchronous colorectal carcinoma in some series. A different management approach and long-term clinical follow-up are recommended for some patients with synchronous colorectal cancer.

Scientific evidence is just the starting point: A generalizable process for developing sports injury prevention interventions

Background: The 2 most cited sports injury prevention research frameworks incorporate intervention development, yet little guidance is available in the sports science literature on how to undertake this complex process. This paper presents a generalizable process for developing implementable sports injury prevention interventions, including a case study applying the process to develop a lower limb injury prevention exercise training program(Footy First) for community Australian football.Methods: The intervention development process is underpinned by 2 complementary premises:(1) that evidence-based practice integrates the best available scientific evidence with practitioner expertise and end user values and(2) that research evidence alone is insufficient to develop implementable interventions.Results: The generalizable 6-step intervention development process involves(1) compiling research evidence, clinical experience, and knowledge of the implementation context;(2) consulting with experts;(3) engaging with end users;(4) testing the intervention;(5) using theory; and(6)obtaining feedback from early implementers. Following each step, intervention content and presentation should be revised to ensure that the final intervention includes evidence-informed content that is likely to be adopted, properly implemented, and sustained over time by the targeted intervention deliverers. For Footy First, this process involved establishing a multidisciplinary intervention development group, conducting 2targeted literature reviews, undertaking an online expert consensus process, conducting focus groups with program end users, testing the program multiple times in different contexts, and obtaining feedback from early implementers of the program.Conclusion: This systematic yet pragmatic and iterative intervention development process is potentially applicable to any injury prevention topic across all sports settings and levels. It will guide researchers wishing to undertake intervention development.

Incidence and mortality of female breast cancer in the AsiaPacific region

Objective: To provide an overview of the incidence and mortality of female breast cancer for countries in the Asia-Pacific region.Methods: Statistical information about breast cancer was obtained from publicly available cancer registry and mortality databases(such as GLOBOCAN), and supplemented with data requested from individual cancer registries. Rates were directly age-standardised to the Segi World Standard population and trends were analysed using joinpoint models.Results: Breast cancer was the most common type of cancer among females in the region, accounting for 18% of all cases in 2012, and was the fourth most common cause of cancer-related deaths(9%). Although incidence rates remain much higher in New Zealand and Australia, rapid rises in recent years were observed in several Asian countries. Large increases in breast cancer mortality rates also occurred in many areas, particularly Malaysia and Thailand, in contrast to stabilising trends in Hong Kong and Singapore, while decreases have been recorded in Australia and New Zealand. Mortality trends tended to be more favourable for women aged under 50 compared to those who were 50 years or older. Conclusion: It is anticipated that incidence rates of breast cancer in developing countries throughout the Asia-Pacific region will continue to increase. Early detection and access to optimal treatment are the keys to reducing breast cancerrelated mortality, but cultural and economic obstacles persist. Consequently, the challenge is to customise breast cancer control initiatives to the particular needs of each country to ensure the best possible outcomes.

Oncogene GAEC1 regulates CAPN10 expression which predicts survival in esophageal squamous cell carcinoma

AIM: To identify the downstream regulated genes of GAEC1 oncogene in esophageal squamous cell carcinoma and their clinicopathological significance. METHODS: The anti-proliferative effect of knocking down the expression of GAEC1 oncogene was stud-ied by using the RNA interference (RNAi) approach through transfecting the GAEC1 -overexpressed esophageal carcinoma cell line KYSE150 with the pSilencer vector cloned with a GAEC1 -targeted sequence, followed by MTS cell proliferation assay and cell cycle analysis using flow cytometry. RNA was then extracted from the parental, pSilencer-GAEC1 -targeted sequence transfected and pSilencer negative control vector transfected KYSE150 cells for further analysis of different patterns in gene expression. Genes differentially expressed with suppressed GAEC1 expression were then determined using Human Genome U133 Plus 2.0 cDNA microarray analysis by comparing with the parental cells and normalized with the pSilencer negative control vector transfected cells. The most prominently regulated genes were then studied by immunohistochemical staining using tissue microarrays to determine their clinicopathological correlations in esophageal squamous cell carcinoma by statistical analyses. RESULTS: The RNAi approach of knocking down gene expression showed the effective suppression of GAEC1 expression in esophageal squamous cell carcinoma cell line KYSE150 that resulted in the inhibition of cell proliferation and increase of apoptotic population. cDNA microarray analysis for identifying differentially expressed genes detected the greatest levels of downregulation of calpain 10 (CAPN10 ) and upregulation of trinucleotide repeat containing 6C (TNRC6C ) transcripts when GAEC1 expression was suppressed. At the tissue level, the high level expression of calpain 10 protein was significantly associated with longer patient survival (month) of esophageal squamous cell carcinoma compared to the patients with low level of calpain 10 expression (37.73 ± 16.33 vs 12.62 ± 12.44, P = 0.032). No significant correction was observed among the TNRC6C protein expression level and the clinocopathologcial features of esophageal squamous cell carcinoma. CONCLUSION: GAEC1 regulates the expression of CAPN10 and TNRC6C downstream. Calpain 10 expression is a potential prognostic marker in patients with esophageal squamous cell carcinoma.

Psycho-Social Predictors of Childbirth Fear in Pregnant Women: An Australian Study

Background: Around 20% of birthing women report high levels of childbirth fear. Fear potentially impacts women’s emotional health, preparation for birth, and birth outcomes. Evidence suggests that personal and external factors contribute to childbirth fear, however results vary. Aim: To identify pyscho-social factors associated with childbirth fear and possible antenatal predictors of childbirth fear according to women’s parity. Method: 1410 women in second trimester and attending one of three public hospitals in south-east Queensland were screened for childbirth fear using the Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ). Other measures included the Edinburgh Depression Scale (EPDS), Decisional Conflict Scale (DCS) and items from the EuroQol (EQ-5D) targeting Anxiety/Depression and Pain/Discomfort. In addition items measuring a previous mental health condition, social support and knowledge were used. Preferred mode of birth was also collected. Psycho-social factors were analysed to determine associations with childbirth fear. Multivariate analysis was used to determine predictors of fear. Results: Thirty-one percent (n = 190/604) of nulliparous and 18% (n = 143/782) of multiparous women reported high fear levels. Having a mental health history, desiring a caesarean section, reporting moderate to high pain during pregnancy, having a non-supportive partner and perceiving less childbirth knowledge than peers, were associated with childbirth fear. Standard multiple regression analyses by parity determined that depression, decisional conflict, low social support and less perceived knowledge predicted levels of childbirth fear. The model explained 32.4% of variance in childbirth fear for nulliparous and 29.4% for multiparous women. Conclusion: Psychosocial factors are significantly associated with childbirth fear. The identification of predictive psychosocial factors for childbirth fear indicates the importance of observing, assessing, and developing support strategies for women. Such strategies are required to decrease anxiety and depression for women during pregnancy, promote normal birth, and build social support to improve women’s feelings and positive expectations of birth.

Blood rheology and aging

The flow properties of blood play significant roles in tissue perfusion by contributing to hydrodynamic resistance in blood vessels. These properties are influenced by pathophysiological processes, thereby increasing the clinical relevance of blood rheology information. There is well-established clinical evidence for impaired blood fluidity in humans of advanced age, including enhanced plasma and whole blood viscosity, impaired red blood cell (RBC) deformability and enhanced RBC aggregation. Increased plasma fibrinogen concentration is a common finding in many studies owing to the pro-inflammatory condition of aged individuals;this finding of increased fibrinogen concen-tration explains the higher plasma viscosity and RBC aggregation in elderly subjects. Enhanced oxidant stress in advanced age is also known to contribute to altered blood fluidity, with RBC deformability being an important determinant of blood viscosity. Several studies have shown that physical activity may improve the hemorheological picture in elderly subjects, yet well-designed observational and mechanistic studies are required to determine the specific effects of regular exercise on hemorheological parameters in healthy and older individuals.

The Effects of Influenza Vaccination on Immune Function in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Immune dysfunction is a hallmark of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). The purpose of this pilot study was to identify the effects of influenza vaccination on immune function in patients with CFS/ME. We included 7 patients meeting the Centre for Disease Control and Prevention criteria (CDC 1994) for ME/CFS and 8 control subjects. Bloods were collected from all participants prior to vaccination with Influvac, a trivalent inactivated influenza vaccine (TIV), 14 and 28 days following vaccination. The immune parameters examined include Natural Killer (NK) phenotypes, NK cytotoxic activity, FOXP3 and Th1/Th2/Th17 related cytokines. Flow cytometric protocols were employed. There was no significant difference in NK phenotypes and Tregs numbers between CFS/ME patients and healthy controls. However, NK activity was significantly decreased at baseline and at 28 days, while at 14 days it significantly increased in the CFS/ME patients compared to the healthy controls. Th1 pro-inflammatory cytokines increased considerably in the CFS/ME patients at 28 days compared to the non-fatigued controls. Only one Th2 cytokine, IL-4, increased in the CFS/ME participants. FOXP3 expressing Tregs only increased significantly at day 28 post vaccination in the CFS/ME patients compared to the healthy controls. Self-rated wellbeing was lower for patients at day 28 while at baseline and day 14 no differences were observed. In this pilot study immunization with influenza vaccine is accompanied by a degree of immune dysregulation in CFS/ME patients compared with controls. While vaccination may protect CFS/ME patients against influenza, it has the ability to increase cytotoxic activity and pro-inflammatory reactions post vaccination. The role of Tregs in promoting a toxic effect at 28 days post-vaccination in our patient group cannot be ruled out. The benefits of influenza vaccine still likely outweigh the risks CFS/ME patients experience following vaccination.

Seasonal variation and living alone are related to pulmonary rehabilitation non-completion

AIM: To identify baseline characteristics that independently predict pulmonary rehabilitation non-completion and compare these findings against the participant's reasons for non-completion. METHODS: Participants with chronic obstructive pulmonary disease(COPD) who attended a standardised twice weekly, eight week pulmonary rehabilitation program(located in the sub-tropics, latitude 27°29' South) between 2010 and 2012 were recruited. Thebaseline characteristics of program completers and non-completers were compared in a case-controlled design. Participants who attended < 12/16 sessions were classified as a non-completer. Non-completers(those who missed > 4 session of the program) were asked by one independent investigator to participate in a survey about their pulmonary rehabilitation experience. Baseline characteristics were assessed for differences between program completers and non-completers. The baseline characteristics included disease severity, exercise capacity, smoking history, participant's social support and the season when each participant commenced rehabilitation. Non-completers that agreed to participate in the survey were asked to indicate what personal factors or external factors contributed to their program non-completion. Comparisons of completers and non-completers baseline characteristics were performed using cross-tabulations and t-tests, with significant measures analysed in a multivariate binary logistic regression model. Non-completers survey responses were compared to the identified independent predictors using cross-tabulations.RESULTS: Twenty-six participants(23.4%) of the 111 participants with COPD [(mean ± SD) age was 67.4 ± 9.2 years and FEV1 54.6% ± 22.3%)], were classified as non-completers. Forty-five participants(40.5%) commenced pulmonary rehabilitation during winter. Thirty-six participants(32.4%) were living alone at program commencement. In the multivariate analysis(n = 111), only programs that commenced in winter(Exp B: 0.255, 95%CI: 0.090-0.727, P = 0.011) and participants that lived alone(Exp B: 2.925, 95%CI: 1.039-8.229, P = 0.042) were identified as independent predictors of program non-completion. Twenty participants of the twenty-six non-completers agreed to participate in the survey about their pulmonary rehabilitation experience. The reasons given for non-completion were grouped into: medical reasons(75%), other personal reasons(30%) and external barriers(45%), with ten non-completers reporting more than one reason.No participant reported living alone or that the program commenced during winter as a reason for noncompletion. There was no relationship between illness being the participant's reason for non-completion and the programs that commenced in winter(P = 0.135). CONCLUSION: Despite winter commencing programs and participants who lived alone being independent predictors of program non-completion, neither measure was reported by participants as a reason for noncompletion.

Enhanced Gene Expression Following Vaccination in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Vaccines have been shown to cause differential expression of genes and increase antibody titers against antigens. Influenza vaccines may have an effect on unexplained disorders such as Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). Immunological changes have been identified following immunization with trivalent influenza vaccine (TIV). The objective of this pilot study was to examine the consequences of TIV on cytokine and cytotoxic genes in CFS/ME. Peripheral blood mononuclear cells were preferentially isolated from whole blood of 7 CFS/ME patients and 8 controls. Following total RNA extraction and synthesis of cDNA, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression levels of mRNAs for cytotoxic genes (perforin (PRF1), granzyme A (GZMA), granzyme B (GZMB) and cytokine genes. GZMB was significantly increased overall in the CFS/ME patients compared to the controls. GZMA was significantly increased 28 days after vaccination while PRF1 was reduced prevaccination but increased 14 days post-vaccination in the CFS/ME patients. There were no significant changes in cytokine genes pre or post vaccination. Administration of TIV may increase the expression of lytic genes in CFS/ME and this may contribute to the increase in cytotoxic activity we observed in these patients post vaccination.

前瞻记忆和警觉性的关系:来自ERP研究的证据

前瞻记忆指记住将来的计划或意图的能力;警觉性是指在一段相对长的时间内保持注意的能力.一般来说,前瞻记忆都包含有警觉性成分.在一般的前瞻记忆任务中,被试先形成一个前瞻记忆的意图,在形成意图之后,不是立即实现这个意图,

Relationship between prospective memory and vigilance: Evidence from ERP

Event-related potentials (ERPs) were used in this study to investigate the neural correlates of prospective memory (PM) and vigilance. Twenty college or graduate students participated in this study. They were administered a PM and a vigilance task and physiological data were collected at the same time. Behavioral results showed that the RT associated with PM cues was longer than those associated with vigilance targets. ERP results showed that PM cues and vigilance targets did not show significant difference in the N2 but PM cues evoked greater N300 than vigilance targets, and vigilance targets evoked greater parietal positivity/P3 than PM cues, suggesting vigilance and PM have similar but also distinctive neural basis.