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Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
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The cost of many topical prescription medications has increased in recent years. We have calculated that the cost per unit now exceeds that of many ?valuable' consumer items.
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We have demonstrated that CDO1 methylation is frequently found in various cancers, including esophageal squamous cell carcinoma (ESCC), but its clinical relevance has remained elusive. CDO1 methylation was investigated in 169 ESCC patients who underwent esophagectomy between 1996 and 2007. CDO1 methylation was assessed by Q-MSP (quantitative methylation specific PCR), and its clinical significance, including its relationship to prognosis, was analyzed. (i) The median TaqMeth value of CDO1 methylation was 9.4, ranging from 0 to 279.5. CDO1 methylation was significantly different between cStage I and cStage II/III (P = 0.02). (ii) On the log-rank plot, the optimal cut-off value was determined to be 8.9; ESCC patients with high CDO1 methylation showed a significantly worse prognosis than those with low CDO1 methylation (P = 0.02). (iii) A multivariate Cox proportional hazards model identified only CDO1 hypermethylation as an independent prognostic factor (HR 2.00, CI 1.09–3.78, P = 0.03). (iv) CDO1 hypermethylation stratified ESCC patients' prognosis in cStage II/III for both neoadjuvant chemo(radio)therapy (NAC)-positive and NAC-negative cases. Moreover, the CDO1 methylation level was significantly lower in cases with Grade 2/3 than in those with Grade 0/1 (P = 0.02) among cStage II/III ESCC patients with NAC. Promoter DNA hypermethylation of CDO1 could be an independent prognostic factor in ESCC; it may also reflect NAC eradication of tumor cells in the primary tumors.
Topical negative pressure is widely used in the management of superficial wounds. The use of this technology in the management of oesophageal perforations is becoming increasingly common. This systematic review aims to capture available evidence about its use in this setting. Medline and Embase were searched using MeSH terms and free text: esophageal perforation; esophageal injury; vacuum assisted closure; vacuum therapy device; esophagus; wounds penetrating; esophageal perforation; wound healing; negative pressure wound therapy. Searches were carried out between April and November 2015. Case series, cohort trials and controlled trials were included. Additional studies were found by hand searching reference lists. Eleven studies met the inclusion criteria with 180 patients. Nine of the studies were case series and two were retrospective comparisons of negative pressure with stents or clips. Healing of the perforation occurred in 163/179 patients and the overall mortality was 12.8%. Compared with published data on mortality from oesophageal perforation, the application of negative pressure appears to be beneficial. The studies are, however, limited to case series and retrospective cohort studies. The number of patients in each study is small and in the absence of randomized trials demonstrating a lack of bias firm conclusions cannot be made.
The aim of this study was to evaluate the effectiveness and toxicities of three-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), and volumetric-modulated arc therapy (VMAT) in patients with cervical esophageal cancer. Specifically, we asked whether technological advances conferred an advantage with respect to the clinical curative effect. Seventy-eight patients with cervical esophageal cancer treated with definitive radiotherapy with or without concomitant chemotherapy at our institution between 2007 and 2014 were enrolled in the study: 26 received 3DCRT, 30 were treated with IMRT, and 22 underwent VMAT. Kaplan–Meier analysis and the Cox proportional hazard model were used to analyze overall survival (OS) and failure-free survival (FFS). Treatment-related toxicity was also assessed. For all patients, the 2-year OS and FFS rates were 56.2 and 53.9%, respectively. The 2-year OS for the 3DCRT, IMRT, and VMAT groups was 53.6, 55.6, and 60.6%, respectively (P = 0.965). The corresponding 2-year FFS rates were 49.5, 56.7, and 60.1% (P = 0.998). A univariate analysis of the complete response to treatment showed an advantage of treatment modality with respect to OS (P < 0.001). The development of acute hematologic toxicity was not significantly different among the three groups. The survival rates of patients treated with IMRT and VMAT were comparable to the survival of patients administered 3DCRT, while lower lung mean dose, V20, maximum dose of brachial plexus and spinal cord. Grade 1 radiation pneumonitis occurred significantly less in patients treated with IMRT and VMAT than with 3DCRT (P = 0.011). A complete response was the most important prognostic factor of the patients with cervical esophageal cancer.
Routine use of nasogastric tubes for gastric decompression has been abolished in nearly all types of gastro-intestinal surgery after introduction of enhanced recovery after surgery programs. However, in esophagectomy the routine use of nasogastric decompression is still a matter of debate. To determine the effects of routine nasogastric decompression following esophagectomy compared with early or peroperative removal of the nasogastric tube on pulmonary complications, anastomotic leakage, mortality, and postoperative recovery. A systematic literature review and meta-analysis of studies comparing early or peroperative versus late removal of nasogastric tubes. A total of seven comparative studies were included (n = 608). In two randomized trials, and one retrospective cohort study, peroperative removal of the nasogastric tube was compared with routine nasogastric decompression. In one randomized trial early removal of the nasogastric tube (on postoperative day 2) was compared with removal of the nasogastric tube on the 6th–10th postoperative day. In the remaining three trials a fast-track protocol without a nasogastric tube was compared with conventional care with a nasogastric tube during the first postoperative days. Peroperative or early removal of the nasogastric tube did not result in a significantly different rate of anastomotic leakage, pulmonary complications or mortality in individual studies, nor in the meta-analysis. In the meta-analysis, hospital stay was significantly shorter with peroperative or early removal of the nasogastric tube when all studies were included, but not when the meta-analysis was limited to randomized trials. This systematic review did not find a difference in adverse outcomes between nasogastric decompression or no nasogastric decompression following esophagectomy.
The purpose of this study is to evaluate the distribution of thyrotropin (TSH) values in patients with autonomously functioning thyroid nodules and to set a TSH threshold above which thyroid scintigraphy would be obviated. Four hundred fifty one patients were included in the present study. Inclusion criteria were age > 18 years, TSH levels between 0.40 and 4.0 mIU/L, detection of a single solid or predominantly solid thyroid nodule >10 mm in the longest diameter. Thyroid ultrasound and thyroid scintigraphy with 99mTc-pertechnetate were performed concurrently in all patients. Among 451 enrolled patients, 173 (38 %) had an autonomously functioning thyroid nodules, of which 137 (79 %) with a normal TSH level. Demographic data and nodules' volume were not significantly different in patients with autonomously functioning thyroid nodules and non-functioning nodules, respectively. However, TSH levels were nonetheless significantly lower in patients with autonomously functioning thyroid nodules compared to those with non-functioning nodules (p < 0.001). Adopting a TSH cutoff level at 2.38 mUI/L, all autonomously functioning thyroid nodules were correctly identified (i.e., 100 % sensitivity) with a 100 % negative predictive value. Our study showed a very high prevalence of autonomously functioning thyroid nodules in mildly iodine-deficient regions and confirmed that serum TSH is not an effective screening test to diagnose an autonomously functioning thyroid nodules. Our data add arguments in favor of the first-line use of thyroid scintigraphy to assess thyroid nodules, at least in iodine deficient areas. As all scintigraphically detected autonomously functioning thyroid nodules had a TSH level below 2.38 mUI/L, a thyroid scintigraphy should be omitted when higher TSH values are found in patients carrying a thyroid nodule.
Publication date: Available online 14 September 2016
Source:The Kaohsiung Journal of Medical Sciences
Author(s): Shu-Chi Wang, Jeng-Fu Yang, Chao-Ling Wang, Chung-Feng Huang, Yu-Yin Lin, Yi-You Chen, Chung-Ting Lo, Po-Yen Lee, Kuan-Ta Wu, Chia-I. Lin, Meng-Hsuan Hsieh, Hung-Yi Chuang, Chi-Kung Ho, Ming-Lung Yu, Chia-Yen Dai
Chronic infection by hepatitis C virus (HCV) is a major risk factor for the development of hepatocellular carcinoma (HCC). Despite the clear clinical importance of virus-associated HCC, the underlying molecular mechanisms remain largely unclarified. Oxidative stress, in particular, DNA lesions associated with oxidative damage, plays a major role in carcinogenesis, and is strongly linked to the development of many cancers, including HCC. However, in identifying hepatocytes with HCV viral RNA, estimates of the median proportion of HCV-infected hepatocytes have been found as high as 40% in patients with chronic HCV infection. In order to explore the gene alternation and association between different viral loads of HCV-infected cells, we established a method to dissect high and low viral load cells and examined the expression of DNA damage-related genes using a quantitative polymerase chain reaction array. We found distinct expression patterns of DNA damage-related genes between high and low viral load cells. This study provides a new method for future study on virus-associated gene expression research.
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Publication date: December 2016
Source:Research in Developmental Disabilities, Volume 59
Author(s): Louise Edgington, Vivian Hill, Elizabeth Pellicano
BackgroundUnusual reactions to sensory input now form part of the diagnostic criteria for autism. These features are common and can have an often-devastating impact on autistic individuals and their families. Yet there are few validated interventions that help to remediate or support autistic individuals' adverse sensory experiences. To date, both measurement of sensory experiences and the resulting interventions have been based on assumptions of neurological sensitivities and largely ignored the role of cognition. This study therefore sought to assess the feasibility of a new 8-week CBT-based group intervention for self-regulation of sensory processing difficulties.MethodSeven cognitively able adolescents diagnosed with autism aged 11–16 years from one mainstream secondary school received the 8-week intervention. Measures of sensory reactivity, anxiety and repetitive behaviours were taken at baseline, post-intervention and follow-up, 8 weeks after the intervention had ceased. Semi-structured interviews and focus groups were also conducted with adolescents and their parents to examine further the acceptability of the intervention.ResultsThe results showed that the intervention itself was feasible – both in its implementation and its acceptability to participants. Qualitative analysis clearly showed that the intervention was effective in raising meta-conscious awareness and self-regulation in these autistic adolescents. Analysis of outcome variables showed no significant change over the intervention period, although effect sizes were moderate-to-large.ConclusionsThese preliminary results are encouraging and should inform the design of a future pilot randomized controlled trial to test its efficacy with a larger group of participants.
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Publication date: Available online 14 September 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): F. Passariello
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The Journal of Clinical Endocrinology &Metabolism, Early Release.
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The Journal of Clinical Endocrinology &Metabolism, Early Release.
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Inflammation contributes to the development of metabolic and cardiovascular disease. Cushing's disease (CD), a state of chronic glucocorticoid (GC) excess characterized by visceral obesity and insulin resistance, may be associated with increased systemic inflammation. Cardiovascular mortality in CD remains elevated even after successful remission. It is unclear if a chronic low grade inflammatory state persists even after remission of CD, which may account for the increased CVD mortality.
1) To assess circulating pro-inflammatory cytokines in active CD patients and BMI-matched controls; 2) to prospectively follow plasma cytokine concentrations in CD patients before and after surgical remission; and 3) to assess if plasma cytokine concentrations correlate with adipose tissue distribution and ectopic lipid content in liver and muscle.
Plasma cytokines from prospectively enrolled CD patients (N=31) were quantified during active disease (v1) vs. controls (N=18), and 19.5±12.9 months after surgical remission (v2). Fasting plasma IL-6, IL-1β, TNF-α, IL-8, IL-17 and IL-10 were quantified using a multiplex assay. Total and regional fat masses were measured by whole-body MRI.
Circulating IL-6 and IL-1β were elevated in active CD patients vs. controls (p<0.05), and remained elevated in CD after surgical remission, despite decreases in BMI (p<0.001), HOMA-IR (p<0.001), and visceral, hepatic, and inter-muscular fat (p<0.001, <0.001 and 0.03, respectively).
Despite long-term remission and improvements in fat distribution and insulin sensitivity, patients with CD may suffer from a state of chronic low-grade inflammation, which could contribute to increased cardiovascular mortality.
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Publication date: Available online 14 September 2016
Source:Free Radical Biology and Medicine
Author(s): Michelle L. Booze, Jason M. Hansen, Peter F. Vitiello
Thiol switches are important regulators of cellular signaling and are coordinated by several redox enzyme systems including thioredoxins, peroxiredoxins, and glutathione. Thioredoxin-1 (Trx1), in particular, is an important signaling molecule not only in response to redox perturbations, but also in cellular growth, regulation of gene expression, and apoptosis. The active site of this enzyme is a highly conserved C-G-P-C motif and the redox mechanism of Trx1 is rapid which presents a challenge in determining specific substrates. Numerous in vitro approaches have identified Trx1-dependent thiol switches; however, these findings may not be physiologically relevant and little is known about Trx1 interactions in vivo. In order to identify Trx1 targets in vivo, we generated a transgenic mouse with inducible expression of a mutant Trx1 transgene to stabilize intermolecular disulfides with protein substrates. Expression of the Trx1 "substrate trap" transgene did not interfere with endogenous thioredoxin or glutathione systems in brain, heart, lung, liver, and kidney. Following immunoprecipitation and proteomic analysis, we identified 41 homeostatic Trx1 interactions in perinatal lung, including previously described Trx1 substrates such as members of the peroxiredoxin family and collapsin response mediator protein 2. Using perinatal hyperoxia as a model of oxidative injury, we found 17 oxygen-induced interactions which included several cytoskeletal proteins which may be important to alveolar development. The data herein validates this novel mouse model for identification of tissue- and cell-specific Trx1-dependent pathways that regulate physiological signals in response to redox perturbations.
Publication date: Available online 13 September 2016
Source:Dental Materials
Author(s): Oleh Andrukhov, Rebecca Huber, Bin Shi, Simon Berner, Xiaohui Rausch-Fan, Andreas Moritz, Nicholas D. Spencer, Andreas Schedle
ObjectivesTitanium surface roughness is recognized as an important parameter influencing osseointegration. However, studies concerning the effect of well-defined surface topographies of titanium surfaces on osteoblasts have been limited in scope. In the present study we have investigated how Ti surfaces of different micrometer-scale roughness influence proliferation, migration, and differentiation of osteoblasts in-vitro.MethodsTitanium replicas with surface roughnesses (Ra) of approximately 0, 1, 2, and 4μm were produced and MG-63 osteoblasts were cultured on these surfaces for up to 5 days. The effect of surface micrometer-scale roughness on proliferation, migration in time-lapse microscopy experiments, as well as the expression of alkaline phosphatase, osteocalcin, vascular-endothelial growth factor (VEGF), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL) were investigated.ResultsProliferation of MG-63 cells was found to decrease gradually with increasing surface roughness. However, the highest expression of alkaline phosphatase, osteocalcin and VEGF was observed on surfaces with Ra values of approximately 1 and 2μm. Further increase in surface roughness resulted in decreased expression of all investigated parameters. The cell migration speed measured in time-lapse microscopy experiments was significantly lower on surfaces with a Ra value of about 4μm, compared to those with lower roughness. No significant effect of surface roughness on the expression of OPG and RANKL was observed.SignificanceThus, surfaces with intermediate Ra roughness values of 1–2μm seem to be optimal for osteoblast differentiation. Neither proliferation nor differentiation of osteoblasts appears to be supported by surfaces with higher or lower Ra values.
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