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1.
Tripathi SC Matta A Kaur J Grigull J Chauhan SS Thakar A Shukla NK Duggal R Choudhary AR Dattagupta S Sharma MC Ralhan R Siu KW 《PloS one》2011,6(5):e19213
Background
In our recent study, tissue proteomic analysis of oral pre-malignant lesions (OPLs) and normal oral mucosa led to the identification of a panel of biomarkers, including prothymosin alpha (PTMA), to distinguish OPLs from histologically normal oral tissues. This study aimed to determine the clinical significance of PTMA overexpression in oral squamous cell hyperplasia, dysplasia and head and neck squamous cell carcinoma (HNSCC).Methodology
Immunohistochemistry of PTMA protein was performed in HNSCCs (n = 100), squamous cell hyperplasia (n = 116), dysplasia (n = 50) and histologically normal oral tissues (n = 100). Statistical analysis was carried out to determine the association of PTMA overexpression with clinicopathological parameters and disease prognosis over 7 years for HNSCC patients.Results
Our immunohistochemical analysis demonstrated significant overexpression of nuclear PTMA in squamous cell hyperplasia (63.8%), dysplasia (50%) and HNSCC (61%) in comparison with oral normal mucosa (ptrend<0.001). Chi-square analysis showed significant association of nuclear PTMA with advanced tumor stages (III+IV). Kaplan Meier survival analysis indicated reduced disease free survival (DFS) in HNSCC patients (p<0.001; median survival 11 months). Notably, Cox-multivariate analysis revealed nuclear PTMA as an independent predictor of poor prognosis of HNSCC patients (p<0.001, Hazard''s ratio, HR = 5.2, 95% CI = 2.3–11.8) in comparison with the histological grade, T-stage, nodal status and tumor stage.Conclusions
Nuclear PTMA may serve as prognostic marker in HNSCC to determine the subset of patients that are likely to show recurrence of the disease. 相似文献2.
3.
Patrick Weller Ivonne Nel Philipp Hassenkamp Thomas Gauler Anke Schlueter Stephan Lang Paulette Dountsop Andreas-Claudius Hoffmann G?tz Lehnerdt 《PloS one》2014,9(12)
Background
Since image based diagnostic tools fail to detect early metastasis in head and neck squamous cell carcinoma (HNSCC) it is crucial to develop minimal invasive diagnostic methods. A promising approach is to identify and characterize circulating tumor cells (CTC) in the peripheral blood of HNSCC patients. In this pilot study, we assessed which non-hematopoietic cell types are identifiable and whether their numbers differ in pre- and postoperative blood samples.Methods
20 ml citrated peripheral blood was taken from 10 HNSCC patients before and after curative resection. CTC were enriched using density gradient centrifugation. CTC presence was verified by multi-immunofluorescence staining against cytokeratin (CK; epithelial), N-cadherin (mesenchymal); CD133 (stem-cell), CD45 (hematopoietic) and DAPI (nucleus). Individual cell type profiles were analyzed.Results
We were able to detect cells with epithelial properties like CK+/N-cadherin−/CD45− and CK+/CD133−/CD45− as well as cells with mesenchymal features such as N-cadherin+/CK−/CD45− and cells with both characteristics like N-cadherin+/CK+/CD45−. We also observed cells showing stem cell-like features like CD133+/CK−/CD45− and cells with both epithelial and stem cell-like features such as CD133+/CK+/CD45−. The number of CK positive cells (p = 0.002), N-cadherin positive cells (p = 0.002) and CD133 positive cells (p = 0.01) decreased significantly after resection. Kaplan-Meier test showed that the survival was significantly shorter when N-cadherin+ cells were present after resection (p = 0.04; 474 vs. 235 days; [HR] = 3.1).Conclusions
This is - to the best of our knowledge- the first pilot study identifying different CTC populations in peripheral blood of HNSCC patients and showing that these individual cell type profiles may have distinct clinical implications. 相似文献4.
Christine van der Leeuw Machteld Marcelis Sanne C. T. Peeters Marcel M. Verbeek Paul P. C. A. Menheere Lieuwe de Haan Jim van Os Nico J. M. van Beveren for Genetic Risk Outcome in Psychosis 《PloS one》2013,8(12)
Background
S100B is a potential marker of neurological and psychiatric illness. In schizophrenia, increased S100B levels, as well as associations with acute positive and persisting negative symptoms, have been reported. It remains unclear whether S100B elevation, which possibly reflects glial dysfunction, is the consequence of disease or compensatory processes, or whether it is an indicator of familial risk.Methods
Serum samples were acquired from two large independent family samples (n = 348 and n = 254) in the Netherlands comprising patients with psychotic disorder (n = 140 and n = 82), non-psychotic siblings of patients with psychotic disorder (n = 125 and n = 94) and controls (n = 83 and n = 78). S100B was analyzed with a Liaison automated chemiluminescence system. Associations between familial risk of psychotic disorder and S100B were examined.Results
Results showed that S100B levels in patients (P) and siblings (S) were not significantly different from controls (C) (dataset 1: P vs. C: B = 0.004, 95% CI −0.005 to 0.013, p = 0.351; S vs. C: B = 0.000, 95% CI −0.009 to 0.008, p = 0.926; and dataset 2: P vs. C: B = 0.008, 95% CI −0.011 to 0.028, p = 0.410; S vs. C: B = 0.002, 95% CI −0.016 to 0.021, p = 0.797). In patients, negative symptoms were positively associated with S100B (B = 0.001, 95% CI 0.000 to 0.002, p = 0.005) in one of the datasets, however with failure of replication in the other. There was no significant association between S100B and positive symptoms or present use or type of antipsychotic medication.Conclusions
S100B is neither an intermediate phenotype, nor a trait marker for psychotic illness. 相似文献5.
Young Ju Lee Kyung Chul Moon Chang Wook Jeong Cheol Kwak Hyeon Hoe Kim Ja Hyeon Ku 《PloS one》2014,9(9)
Purpose
To investigate the prognostic significance of squamous and/or glandular differentiation in urothelial carcinoma (UC).Materials and Methods
Among 800 consecutive patients who underwent radical cystectomy or nephroureterectomy at our institution from January 1990 to December 2010, 696 patients were included for the analysis. Clinicopathologic variables were compared according to the presence of squamous and/or glandular differentiation and the tumor location.Results
A total of 51 (7.3%) patients had squamous and/or glandular differentiation. Patients with squamous and/or glandular differentiation had higher pathological T stage (p<0.001) and grade (p<0.001) than those with pure form of UC. After the median follow-up of 55.2 months, 84 (24.6%) and 82 (23.1%) died of upper urinary tract UC and UC of bladder, respectively. Patients with squamous and/or glandular differentiation in upper urinary tract UC showed poorer cancer-specific survival (CSS) (p<0.001) and overall survival (OS) (p<0.001) than those with pure form in upper urinary tract UC (p<0.001), but not in UC of bladder (p = 0.178 for CSS and p = 0.172 for OS). On multivariate Cox regression analysis, squamous and/or glandular differentiation was an independent predictor of CSS (hazard ratio [HR] 1.76; 95% confidence interval [CI] 1.08–2.85, p = 0.023), but it was not associated with OS (HR 1.52; 95% CI 1.00–2.32, p = 0.051).Conclusions
The presence of variant histology could be associated with poorer survival outcome in patients with UC. Squamous and/or glandular differentiation is associated with features of biologically aggressive disease and an independent predictor of CSS. 相似文献6.
Eirini Pectasides Theodoros Rampias Clarence Sasaki Christos Perisanidis Vassilis Kouloulias Barbara Burtness Thomas Zaramboukas David Rimm George Fountzilas Amanda Psyrri 《PloS one》2014,9(4)
Background
Elucidating the molecular phenotype of cancers with high metastatic potential will facilitate the development of novel therapeutic approaches to the disease. Gene expression profiles link epithelial to mesenchymal transition (EMT) phenotype with high-risk HNSCC. We sought to determine the role of protein biomarkers of EMT in head and neck squamous carcinoma (HNSC) prognosis.Methods
Protein expression analysis of EGFR, β-catenin and E-cadherin was performed on a cohort of 102 patients with HNSCC recruited between 1992 and 2005 using automated quantitative protein analysis (AQUA). We evaluated associations with clinicopathological parameters and prognosis.Results
There were 67 patients with primary squamous cell carcinoma of the head and neck in this cohort who met inclusion criteria and for whom we had complete E-cadherin, beta-catenin and EGFR expression data. High E-cadherin expressers had longer 5-year progression-free survival (PFS) compared to those with low E-cadherin (59.7% versus 40.6%, p = 0.04) and overall survival (OS) (69.6% versus 44.3%, p = 0.05). Kaplan-Meier analysis showed that patients with low beta-catenin-expressing tumors trended toward worse 5-year PFS (p = 0.057). High EGFR expressers had inferior OS compared to low EGFR expressers (27.7% vs. 54%, p = 0.029). In the multivariable analysis context, E-cadherin remained an independent predictor of improved OS (HR = 0.204, 95% CI 0.043 to 0.972, p = 0.046) while EGFR trended towards significance for OS.Conclusions
The putative markers of EMT defined within a panel of HNSCC using AQUA are associated with tumors of poor prognosis. 相似文献7.
Background
Pre-procedural intravenous fluid administration is an effective prophylaxis measure for contrast-induced acute kidney injury. For logistical ease, the oral route is an alternative to the intravenous. The objective of this study was to compare the efficacy of the oral to the intravenous route in prevention of contrast-induced acute kidney injury.Study Design
A systematic review and meta-analysis of randomised trials with a stratified analysis and metaregression. Databases included MEDLINE (1950 to November 23 2011), EMBASE (1947 to week 47 2011), Cochrane CENTRAL (3rd quarter 2011). Two reviewers identified relevant trials and abstracted data.Settings and Population
Trials including patients undergoing a contrast enhanced procedure.Selection Criteria
Randomised controlled trial; adult (>18 years) population; comparison of oral versus intravenous volume expansion.Intervention
Oral route of volume expansion compared to the intravenous route.Outcomes
Any measure of acute kidney injury, need for renal replacement therapy, hospitalization and death.Results
Six trials including 513 patients met inclusion criteria. The summary odds ratio was 1.19 (95% CI 0.46, 3.10, p = 0.73) suggesting no difference between the two routes of volume expansion. There was significant heterogeneity (Cochran’s Q = 11.65, p = 0.04; I2 = 57). In the stratified analysis, inclusion of the five studies with a prespecified oral volume expansion protocol resulted in a shift towards oral volume expansion (OR 0.75, 95% CI 0.37, 1.50, p = 0.42) and also resolved the heterogeneity (Q = 3.19, P = 0.53; I2 = 0).Limitations
Small number of studies identified; lack of hard clinical outcomes.Conclusion
The oral route may be as effective as the intravenous route for volume expansion for contrast-induced acute kidney injury prevention. Adequately powered trials with hard endpoints should be done given the potential advantages of oral (e.g. reduced patient burden and cost) over intravenous volume expansion. 相似文献8.
Trigeminal Neurosensory Deficit and Patient Reported Outcome Measures: The Effect on Quality of Life
Objectives
To investigate the effect of persistent neurosensory disturbance of the lingual nerve (LN) or inferior alveolar nerve (IAN) on general health and oral health- related quality of life (QoL).Methods
The study design was a case-control study. Patients with persistent neurosensory deficit of LN or IAN after lower third molar surgery (for 12 months or more) were the study group. The control group was an age and gender matched sample of patients who had dental extractions or lower third molar surgeries without trigeminal neurosensory deficit. The outcome variables were the general health and oral health-related QoL. General health-related QoL was assessed using the 36-item Short Form Health Survey (SF-36) and oral health-related QoL using the 14-item Short Form Oral Health Impact Profile (OHIP-14). Differences in SF-36 scores and OHIP-14 scores between the groups were compared.Results
Forty-eight subjects (24 cases and 24 controls) were recruited. When compared to the control group, patients with neurosensory deficits had poorer Mental-Health Component Scores (MCS) (p = 0.005), General Health (p = 0.023), Vitality (p = 0.048), Social Functioning (p = 0.003), Role-emotion (p = 0.008) and Mental Health (p = 0.022). The OHIP-14 scores were also significantly worse in this patients with neurosensory deficits compared with the control group (p = 0.002). When compared within the study group, older patient with neurosensory deficit was found to correlate with worse Physical Health Component Scores (PCS) (p = 0.02) and OHIP-14 scores (p = 0.02), while more severe visualized analog scaling rating of numbness was correlated with a worse PCS (p = 0.034).Conclusions
Patients with persistent LN or IAN deficit after lower third molar surgery have poorer health-related QoL and poorer oral health-related QoL than those without such deficits. 相似文献9.
Background
Epidemiologic studies have reported the association of X-ray repair cross-complementary group 1 (XRCC1) Arg399Gln polymorphisms with susceptibility to squamous cell carcinoma of the head and neck (HNSCC). However, the results were conflictive rather than conclusive. The purpose of this study was to clarify the association of XRCC1 Arg399Gln variants with HNSCC risk.Methods
Systematic searches were performed through the search engines of PubMed, Elsevier, Science Direct, CNKI and Chinese Biomedical Literature Database. Summary odds ratio (OR) with 95% confidence intervals (CI) was computed to estimate the strength association.Results
Overall, we did not observe any association of XRCC1 Arg399Gln polymorphisms with HNSCC risk in total population (OR = 0.95, 95% CI: 0.76–1.19 for Gln/Gln vs. Arg/Arg, OR = 1.05, 95% CI: 0.92–1.20 for Arg/Gln vs. Arg/Arg, and OR = 1.03, 95% CI: 0.90–1.18 for Gln/Gln+Arg/Gln vs. Arg/Arg) based on 18 studies including 3917 cases and 4560 controls. In subgroup analyses, we observed an increased risk of XRCC1 399 Arg/Gln genotype for HNSCC in Caucasians (OR = 1.20, 95% CI: 1.00–1.44) and Gln/Gln genotype for larynx squamous cell carcinoma (OR = 1.63, 95% CI: 1.10–2.40). We did not observe any association between XRCC1 Arg399Gln variants and HNSCC risk in additional subgroup analyses.Conclusion
The results from this present meta-analysis suggest that XRCC1 Arg399Gln variants may contribute to HNSCC risk among Caucasians and to the risk of larynx squamous cell carcinoma. Further, well-designed studies with larger sample sizes are required to verify our findings. 相似文献10.
Pilou L. H. R. Janssens Rick Hursel Eveline A. P. Martens Margriet S. Westerterp-Plantenga 《PloS one》2013,8(7)
Background
Addition of capsaicin (CAPS) to the diet has been shown to increase energy expenditure; therefore capsaicin is an interesting target for anti-obesity therapy.Aim
We investigated the 24 h effects of CAPS on energy expenditure, substrate oxidation and blood pressure during 25% negative energy balance.Methods
Subjects underwent four 36 h sessions in a respiration chamber for measurements of energy expenditure, substrate oxidation and blood pressure. They received 100% or 75% of their daily energy requirements in the conditions ‘100%CAPS’, ‘100%Control’, ‘75%CAPS’ and ‘75%Control’. CAPS was given at a dose of 2.56 mg (1.03 g of red chili pepper, 39,050 Scoville heat units (SHU)) with every meal.Results
An induced negative energy balance of 25% was effectively a 20.5% negative energy balance due to adapting mechanisms. Diet-induced thermogenesis (DIT) and resting energy expenditure (REE) at 75%CAPS did not differ from DIT and REE at 100%Control, while at 75%Control these tended to be or were lower than at 100%Control (p = 0.05 and p = 0.02 respectively). Sleeping metabolic rate (SMR) at 75%CAPS did not differ from SMR at 100%CAPS, while SMR at 75%Control was lower than at 100%CAPS (p = 0.04). Fat oxidation at 75%CAPS was higher than at 100%Control (p = 0.03), while with 75%Control it did not differ from 100%Control. Respiratory quotient (RQ) was more decreased at 75%CAPS (p = 0.04) than at 75%Control (p = 0.05) when compared with 100%Control. Blood pressure did not differ between the four conditions.Conclusion
In an effectively 20.5% negative energy balance, consumption of 2.56 mg capsaicin per meal supports negative energy balance by counteracting the unfavorable negative energy balance effect of decrease in components of energy expenditure. Moreover, consumption of 2.56 mg capsaicin per meal promotes fat oxidation in negative energy balance and does not increase blood pressure significantly.Trial Registration
Nederlands Trial Register; registration number NTR2944 相似文献11.
Yung-Che Chen Chang-Chun Hsiao Kuang-Den Chen Yu-Chiang Hung Ching-Yuan Wu Chien-Hao Lie Shih-Feng Liu Ming-Tse Sung Chung-Jen Chen Ting-Ya Wang Jen-Chieh Chang Petrus Tang Wen-Feng Fang Yi-Hsi Wang Yu-Hsiu Chung Tung-Ying Chao Sum-Yee Leung Mao-Chang Su Chin-Chou Wang Meng-Chih Lin 《PloS one》2013,8(2)
Introduction
Increasing evidence has shown that immune surveillance is compromised in a tumor-promoting microenvironment for patients with non-small cell lung cancer (NSCLC), and can be restored by appropriate chemotherapy.Methods
To test this hypothesis, we analyzed microarray gene expression profiles of peripheral blood mononuclear cells from 30 patients with newly-diagnosed advanced stage NSCLC, and 20 age-, sex-, and co-morbidity-matched healthy controls. All the patients received a median of four courses of chemotherapy with cisplatin and gemcitabine for a 28-day cycle as first line treatment.Results
Sixty-nine differentially expressed genes between the patients and controls, and 59 differentially expressed genes before and after chemotherapy were identified. The IL4 pathway was significantly enriched in both tumor progression and chemotherapy signatures. CXCR4 and IL2RG were down-regulated, while DOK2 and S100A15 were up-regulated in the patients, and expressions of all four genes were partially or totally reversed after chemotherapy. Real-time quantitative RT-PCR for the four up-regulated (S100A15, DOK2) and down-regulated (TLR7, TOP1MT) genes in the patients, and the six up-regulated (TLR7, CRISP3, TOP1MT) and down-regulated (S100A15, DOK2, IL2RG) genes after chemotherapy confirmed the validity of the microarray results. Further immunohistochemical analysis of the paraffin-embedded lung cancer tissues identified strong S100A15 nuclear staining not only in stage IV NSCLC as compared to stage IIIB NSCLC (p = 0.005), but also in patients with stable or progressive disease as compared to those with a partial response (p = 0.032). A high percentage of S100A15 nuclear stained cells (HR 1.028, p = 0.01) was the only independent factor associated with three-year overall mortality.Conclusions
Our results suggest a potential role of the IL4 pathway in immune surveillance of advanced stage NSCLC, and immune potentiation of combination chemotherapy. S100A15 may serve as a potential biomarker for tumor staging, and a predictor of poor prognosis in NSCLC. 相似文献12.
Young-Hoon Joo Youn-Soo Lee Kwang-Jae Cho Jun-Ook Park In-Chul Nam Chung-Soo Kim Sang-Yeon Kim Min-Sik Kim 《PloS one》2013,8(11)
Background
High-risk human papillomavirus (HPV) is an oncogenic virus that causes oropharyngeal cancers, and it has a favorable outcome after the treatment. Unlike in oropharyngeal cancer, the prevalence and role of high-risk HPV in the etiology of hypopharyngeal squamous cell carcinoma (HPSCC) is uncertain.Objective
The aim of the present study was to evaluate the effect and prognostic significance of high-risk HPV in patients with HPSCC.Methods
The study included 64 subjects with HPSCC who underwent radical surgery with or without radiation-based adjuvant therapy. Primary tumor sites were the pyriform sinus in 42 patients, posterior pharyngeal wall in 19 patients, and postcricoid area in 3 patients. High-risk HPV in situ hybridization was performed to detect HPV infection.Results
The positive rate of high-risk HPV in situ hybridization was 10.9% (7/64). There was a significant difference in the fraction of positive high-risk HPV among pyriform sinus cancer (16.7%), posterior pharyngeal wall cancer (0%), and postcricoid area cancer (0%) (p = 0.042). The laryngoscopic examination revealed a granulomatous and exophytic appearance in 85.7% (6/7) of patients with high-risk HPV-positive pyriform sinus cancer, but in only 31.4% (11/35) of patients with high-risk HPV-negative pyriform sinus cancer (p = 0.012). Significant correlations were found between positive high-risk HPV and younger age (p = 0.050) and non-smoking status (p = 0.017). HPV-positive patients had a significantly better disease-free survival (p = 0.026) and disease-specific survival (p = 0.047) than HPV-negative patients.Conclusions
High-risk HPV infection is significantly related to pyriform sinus cancer in patients with HPSCC. 相似文献13.
Marcus Lind Jaakko Tuomilehto Matti Uusitupa Olle Nerman Johan Eriksson Pirjo Ilanne-Parikka Sirkka Kein?nen-Kiukaanniemi Markku Peltonen Aldina Pivodic Jaana Lindstr?m 《PloS one》2014,9(10)
Objective
To determine the association between HbA1c, fasting plasma glucose (FPG), 1-hour (1 hPG) and 2-hour (2 hPG) glucose after an oral glucose tolerance test (OGTT) and cardiovascular disease in individuals with elevated risk for diabetes.Design
We studied the relationship between baseline, updated mean and updated (last) value of HbA1c, FPG, 1 hPG and 2 hPG after an oral 75 g glucose tolerance test (OGTT) and acute CVD events in 504 individuals with impaired glucose tolerance (IGT) at baseline enrolled in the Finnish Diabetes Prevention Study.Setting
Follow-up of clinical trial.Participants
504 individuals with IGT were followed with yearly evaluations with OGTT, FPG and HbA1c.Main Outcome Measure
Relative risk of CVD.Results
Over a median follow-up of 9.0 years 34 (6.7%) participants had a CVD event, which increased to 52 (10.3%) over a median follow-up of 13.0 years when including events that occurred among participants following a diagnosis of diabetes. Updated mean HbA1c, 1 hPG and 2 hPG, HR per 1 unit SD of 1.57 (95% CI 1.16 to 2.11), p = 0.0032, 1.51 (1.03 to 2.23), p = 0.036 and 1.60 (1.10 to 2.34), p = 0.014, respectively, but not FPG (p = 0.11), were related to CVD. In analyses of the last value prior to the CVD event the same three glycaemic measurements were associated with the CVD events, with HRs per 1 unit SD of 1.45 (1.06 to 1.98), p = 0.020, 1.55 (1.04 to 2.29), p = 0.030 and 2.19 (1.51 to 3.18), p<0.0001, respectively but only 2 hPG remained significant in pairwise comparisons. Including the follow-up period after diabetes onset updated 2 hPG (p = 0.003) but not updated mean HbA1c (p = 0.08) was related to CVD.Conclusions and Relevance
Current 2 hPG level in people with IGT is associated with increased risk of CVD. This supports its use in screening for prediabetes and monitoring glycaemic levels of people with prediabetes. 相似文献14.
Eliane A. Lucassen Paolo Piaggi John Dsurney Lilian de Jonge Xiong-ce Zhao Megan S. Mattingly Angela Ramer Janet Gershengorn Gyorgy Csako Giovanni Cizza for the Sleep Extension Study Group 《PloS one》2014,9(1)
Background
Sleep deprivation and obesity, are associated with neurocognitive impairments. Effects of sleep deprivation and obesity on cognition are unknown, and the cognitive long-term effects of improvement of sleep have not been prospectively assessed in short sleeping, obese individuals.Objective
To characterize neurocognitive functions and assess its reversibility.Design
Prospective cohort study.Setting
Tertiary Referral Research Clinical Center.Patients
A cohort of 121 short-sleeping (<6.5 h/night) obese (BMI 30–55 kg/m2) men and pre-menopausal women.Intervention
Sleep extension (468±88 days) with life-style modifications.Measurements
Neurocognitive functions, sleep quality and sleep duration.Results
At baseline, 44% of the individuals had an impaired global deficit score (t-score 0–39). Impaired global deficit score was associated with worse subjective sleep quality (p = 0.02), and lower urinary dopamine levels (p = 0.001). Memory was impaired in 33%; attention in 35%; motor skills in 42%; and executive function in 51% of individuals. At the final evaluation (N = 74), subjective sleep quality improved by 24% (p<0.001), self-reported sleep duration increased by 11% by questionnaires (p<0.001) and by 4% by diaries (p = 0.04), and daytime sleepiness tended to improve (p = 0.10). Global cognitive function and attention improved by 7% and 10%, respectively (both p = 0.001), and memory and executive functions tended to improve (p = 0.07 and p = 0.06). Serum cortisol increased by 17% (p = 0.02). In a multivariate mixed model, subjective sleep quality and sleep efficiency, urinary free cortisol and dopamine and plasma total ghrelin accounted for 1/5 of the variability in global cognitive function.Limitations
Drop-out rate.Conclusions
Chronically sleep-deprived obese individuals exhibit substantial neurocognitive deficits that are partially reversible upon improvement of sleep in a non-pharmacological way. These findings have clinical implications for large segments of the US population.Trail registration
www.ClinicalTrials.gov NCT00261898. NIDDK protocol 06-DK-0036 相似文献15.
Nikolaos Tertipis Linnea Haeggblom Cecilia Nordfors Nathalie Grün Anders N?sman Andrea Vlastos Tina Dalianis Torbj?rn Ramqvist 《PloS one》2014,9(4)
Aim
To examine LMP10 expression and its possible impact on clinical outcome in human papillomavirus (HPV) positive and HPV-negative tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC).Background
Outcome is better in HPV-positive TSCC and BOTSCC compared to matching HPV-negative tumours, with roughly 80% vs. 40% 5-year disease free survival (DFS) with less aggressive treatment than today’s chemoradiotherapy. Since current treatment often results in harmful side effects, less intensive therapy, with sustained patient survival would be an attractive alternative. However, other markers together with HPV status are necessary to select patients and for this purpose LMP10 expression is investigated here in parallel to HPV status and clinical outcome.Materials and Methods
From 385 patients diagnosed between 2000 and 2007 at the Karolinska University Hospital, 278 formalin fixed paraffin embedded TSCC and BOTSCC biopsies, with known HPV DNA status, were tested for LMP10 nuclear and cytoplasmic expression (fraction of positive cells and staining intensity). The data was then correlated to clinical outcome.Results
An absent/low compared to a moderate/high LMP10 nuclear fraction of positive cells was correlated to a better 3-year DFS in the HPV-positive group of patients (log-rank p = 0.005), but not in the HPV-negative group. In the HPV-negative group of patients, in contrast to the HPV-positive group, moderate/high LMP10 cytoplasmic fraction and weak/moderate/high LMP10 cytoplasmic intensity correlated to a better 3-year DFS (p = 0.003 and p = 0.001) and 3-year overall survival (p = 0.001 and 0.009).Conclusion
LMP10 nuclear expression in the HPV-positive group and LMP10 cytoplasmic expression in the HPV-negative group of patients correlated to better clinical outcome. 相似文献16.
Teresa A. Ajslev Lars ?ngquist Karri Silventoinen Jennifer L. Baker Thorkild I. A. S?rensen 《PloS one》2014,9(10)
Background
The intergenerational resemblance in body mass index may have increased during the development of the obesity epidemic due to changes in environment and/or expression of genetic predisposition.Objectives
This study investigates trends in intergenerational correlations of childhood body mass index (BMI; kg/m2) during the emergence of the obesity epidemic.Methods
The study population was derived from the Copenhagen School Health Records Register, which includes height and weight measurements since birth year 1930. Mothers and fathers with BMIs available at ages 7 (n = 25,923 and n = 20,972) or 13 years (n = 26,750 and n = 21,397), respectively, were linked through the civil registration system introduced in 1968 to their children with BMIs available at age 7 years. Age- and sex-specific BMI z-scores were calculated. Correlations were estimated across eight intervals of child birth years (1952–1989) separately by sex. Trends in these correlations were examined. Whereas the mother-child correlations reflected the biological relationship, a likely decline in the assignment of non-biological fathers through the registration system across time must be considered when interpreting the father-child correlations.Results
The BMI correlations between mothers and sons ranged from 0.29–0.36 and they decreased marginally, albeit significantly across time at ages 7–7 years (−0.002/year, p = 0.006), whereas those at 13–7 years remained stable (<0.0004/year, p = 0.96). Mother-daughter correlations ranged from 0.30–0.34, and they were stable at ages 7–7 years (0.0001/year, p = 0.84) and at 13–7 years (0.0004/year, p = 0.56). In contrast, father-son correlations increased significantly during this period, both at ages 7–7 (0.002/year, p = 0.007) and at ages 13–7 years (0.003/year, p<0.001), whereas the increase in father-daughter correlations were insignificant both at ages 7–7 (0.001/year, p = 0.37) and at ages 13–7 years (0.001/year, p = 0.18).Conclusion
During the obesity epidemics development, the intergenerational resemblance with mothers remained stable, whereas the father-child BMI resemblance increased, possibly reflecting changes in family relationships, and unlikely to have influenced the epidemic. 相似文献17.
Yohei Fujita Masato Okamoto Hiroyuki Goda Tomoyuki Tano Koh-ichi Nakashiro Atsuro Sugita Tomonobu Fujita Shigeo Koido Sadamu Homma Yutaka Kawakami Hiroyuki Hamakawa 《PloS one》2014,9(12)
Purpose
We investigated whether serum interleukin (IL)-8 reflects the tumor microenvironment and has prognostic value in patients with oral squamous cell carcinoma (OSCC).Experimental Design
Fifty OSCC patients who received radical resection of their tumor(s) were enrolled. Preoperative sera were measured for IL-8 by ELISA. Expression of IL-8 and the infiltration of immune cells in tumor tissues were analyzed by an immunohistochemical staining of surgical specimens.Results
We found that disease-free survival (DFS) was significantly longer in the Stage I/II OSCC patients with low serum IL-8 levels compared to those with high levels (p = 0.001). The tumor expression of IL-8, i.e., IL-8(T) and the density of CD163-positive cells in the tumor invasive front, i.e., CD163(IF) were correlated with the serum IL-8 level (p = 0.033 and p = 0.038, respectively), and they were associated with poor clinical outcome (p = 0.007 and p = 0.002, respectively, in DFS) in all patients. A multivariate analysis revealed that N status, IL-8(T) and CD163(IF) significantly affected the DFS of the patients. Further analysis suggested that combination of N status with serum IL-8, IL-8(T) or CD163(IF) may be a new criterion for discriminating between OSCC patients at high and low risk for tumor relapse. Interestingly, the in vitro experiments demonstrated that IL-8 enhanced generation of CD163-positive M2 macrophages from peripheral blood monocytes, and that the cells produced IL-10.Conclusions
These findings indicate that IL-8 may be involved in poor clinical outcomes via generation of CD163-positive M2 macrophages, and that these factors in addition to N status may have prognostic value in patients with resectable OSCSS. 相似文献18.
Objectives
The Liver X receptors (LXRs), Liver X receptor A (LXRA) and Liver X receptor B (LXRB), regulate lipid metabolism and antimicrobial response. LXRs have a crucial role in the control of Mycobacterium tuberculosis (M.tb). Lacking LXRs mice is more susceptibility to infection M.tb, developing higher bacterial burdens and an increase in the size and number of granulomatous lesions. We aimed to assess the associations between single nucleotide polymorphisms (SNPs) in LXRs and risk of tuberculosis.Methods
We sequenced the LXRs genes to detect SNPs and to examine genotypic frequencies in 600 patients and 620 healthy controls to investigate for associations with tuberculosis (TB) in the Chinese Han population. DNA re-sequencing revealed eight common variants in the LXRs genes.Results
The G allele of rs1449627 and the T allele of rs1405655 demonstrated an increased risk of developing TB (p<0.001, p = 0.002), and the T allele of rs3758673, the T allele of rs2279238, and the C allele of rs1449626 in LXRA and the C allele of rs17373080, the G allele of rs2248949, and the C allele of rs1052677 in LXRB were protective against TB patients compared to healthy controls (p = 0.0002, p = 0.006, p<0.001, p = 0.004, p = 0.008, p = 0.003, respectively). All SNP genotypes were significantly associated with TB. An estimation of the frequencies of haplotypes revealed two potential risk haplotypes,GGCG in LXRB (p = 0.004,) and TTCG in LXRA (p<0.001, p = 0.004). Moreover, three protective haplotypes, TTAT and CCAT in LXRA and CATC in LXRB, were significantly “protective” (p = 0.008, p<0.001, p = 0.031) for TB. Furthermore, we determined that the LXRs SNPs were nominally associated with the clinical pattern of disease.Conclusions
Our study data supported that LXRs play a fundamental role in the genetic susceptibility to TB and to different clinical patterns of disease. Thus, further investigation is required in larger populations and in additional areas. 相似文献19.
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